Sample records for receptor scanning update

  1. Update on melatonin receptors: IUPHAR Review 20.

    PubMed

    Jockers, Ralf; Delagrange, Philippe; Dubocovich, Margarita L; Markus, Regina P; Renault, Nicolas; Tosini, Gianluca; Cecon, Erika; Zlotos, Darius P

    2016-09-01

    Melatonin receptors are seven transmembrane-spanning proteins belonging to the GPCR superfamily. In mammals, two melatonin receptor subtypes exist - MT1 and MT2 - encoded by the MTNR1A and MTNR1B genes respectively. The current review provides an update on melatonin receptors by the corresponding subcommittee of the International Union of Basic and Clinical Pharmacology. We will highlight recent developments of melatonin receptor ligands, including radioligands, and give an update on the latest phenotyping results of melatonin receptor knockout mice. The current status and perspectives of the structure of melatonin receptor will be summarized. The physiological importance of melatonin receptor dimers and biologically important and type 2 diabetes-associated genetic variants of melatonin receptors will be discussed. The role of melatonin receptors in physiology and disease will be further exemplified by their functions in the immune system and the CNS. Finally, antioxidant and free radical scavenger properties of melatonin and its relation to melatonin receptors will be critically addressed. © 2016 The British Pharmacological Society.

  2. Cognitive enhancers (Nootropics). Part 1: drugs interacting with receptors. Update 2014.

    PubMed

    Froestl, Wolfgang; Muhs, Andreas; Pfeifer, Andrea

    2014-01-01

    Scientists working in the fields of Alzheimer's disease and, in particular, cognitive enhancers are very productive. The review "Cognitive enhancers (nootropics): drugs interacting with receptors" was accepted for publication in July 2012. Since then, new targets for the potential treatment of Alzheimer's disease were identified. This update describes drugs interacting with 42 receptors versus 32 receptors in the first paper. Some compounds progressed in their development, while many others were discontinued. The present review covers the evolution of research in this field through March 2014.

  3. Update in TSH Receptor Agonists and Antagonists

    PubMed Central

    Neumann, Susanne

    2012-01-01

    The physiological role of the TSH receptor (TSHR) as a major regulator of thyroid function is well understood, but TSHRs are also expressed in multiple normal extrathyroidal tissues, and the physiological roles of TSHRs in these tissues are unclear. Moreover, TSHRs play a major role in several pathological conditions including hyperthyroidism, hypothyroidism, and thyroid tumors. Small molecule, “drug-like” TSHR agonists, neutral antagonists, and inverse agonists may be useful as probes of TSHR function in extrathyroidal tissues and as leads to develop drugs for several diseases of the thyroid. In this Update, we review the most recent findings regarding the development and use of these small molecule TSHR ligands. PMID:23019348

  4. An empirical Bayes method for updating inferences in analysis of quantitative trait loci using information from related genome scans.

    PubMed

    Zhang, Kui; Wiener, Howard; Beasley, Mark; George, Varghese; Amos, Christopher I; Allison, David B

    2006-08-01

    Individual genome scans for quantitative trait loci (QTL) mapping often suffer from low statistical power and imprecise estimates of QTL location and effect. This lack of precision yields large confidence intervals for QTL location, which are problematic for subsequent fine mapping and positional cloning. In prioritizing areas for follow-up after an initial genome scan and in evaluating the credibility of apparent linkage signals, investigators typically examine the results of other genome scans of the same phenotype and informally update their beliefs about which linkage signals in their scan most merit confidence and follow-up via a subjective-intuitive integration approach. A method that acknowledges the wisdom of this general paradigm but formally borrows information from other scans to increase confidence in objectivity would be a benefit. We developed an empirical Bayes analytic method to integrate information from multiple genome scans. The linkage statistic obtained from a single genome scan study is updated by incorporating statistics from other genome scans as prior information. This technique does not require that all studies have an identical marker map or a common estimated QTL effect. The updated linkage statistic can then be used for the estimation of QTL location and effect. We evaluate the performance of our method by using extensive simulations based on actual marker spacing and allele frequencies from available data. Results indicate that the empirical Bayes method can account for between-study heterogeneity, estimate the QTL location and effect more precisely, and provide narrower confidence intervals than results from any single individual study. We also compared the empirical Bayes method with a method originally developed for meta-analysis (a closely related but distinct purpose). In the face of marked heterogeneity among studies, the empirical Bayes method outperforms the comparator.

  5. Modular scanning FCS quantifies receptor-ligand interactions in living multicellular organisms.

    PubMed

    Ries, Jonas; Yu, Shuizi Rachel; Burkhardt, Markus; Brand, Michael; Schwille, Petra

    2009-09-01

    Analysis of receptor-ligand interactions in vivo is key to biology but poses a considerable challenge to quantitative microscopy. Here we combine static-volume, two-focus and dual-color scanning fluorescence correlation spectroscopy to solve this task at cellular resolution in complex biological environments. We quantified the mobility of fibroblast growth factor receptors Fgfr1 and Fgfr4 in cell membranes of living zebrafish embryos and determined their in vivo binding affinities to their ligand Fgf8.

  6. A Review of the Updated Pharmacophore for the Alpha 5 GABA(A) Benzodiazepine Receptor Model

    PubMed Central

    Clayton, Terry; Poe, Michael M.; Rallapalli, Sundari; Biawat, Poonam; Savić, Miroslav M.; Rowlett, James K.; Gallos, George; Emala, Charles W.; Kaczorowski, Catherine C.; Stafford, Douglas C.; Arnold, Leggy A.; Cook, James M.

    2015-01-01

    An updated model of the GABA(A) benzodiazepine receptor pharmacophore of the α5-BzR/GABA(A) subtype has been constructed prompted by the synthesis of subtype selective ligands in light of the recent developments in both ligand synthesis, behavioral studies, and molecular modeling studies of the binding site itself. A number of BzR/GABA(A) α5 subtype selective compounds were synthesized, notably α5-subtype selective inverse agonist PWZ-029 (1) which is active in enhancing cognition in both rodents and primates. In addition, a chiral positive allosteric modulator (PAM), SH-053-2′F-R-CH3 (2), has been shown to reverse the deleterious effects in the MAM-model of schizophrenia as well as alleviate constriction in airway smooth muscle. Presented here is an updated model of the pharmacophore for α5β2γ2 Bz/GABA(A) receptors, including a rendering of PWZ-029 docked within the α5-binding pocket showing specific interactions of the molecule with the receptor. Differences in the included volume as compared to α1β2γ2, α2β2γ2, and α3β2γ2 will be illustrated for clarity. These new models enhance the ability to understand structural characteristics of ligands which act as agonists, antagonists, or inverse agonists at the Bz BS of GABA(A) receptors. PMID:26682068

  7. A2A adenosine receptor agonists and their potential therapeutic applications. An update.

    PubMed

    Guerrero, Angel

    2018-03-12

    In the last 20 years, an increasing interest of medicinal chemists on the development of potent and selective agonists and antagonists of adenosine receptors has been noticed due to the large impact they have shown in a variety of important biological processes and diseases. Among these, it should be mentioned vasodilation, inflammation, cancer, wound healing, ischemia reperfusion injury, Parkinson disease, infectious diseases, and other CNS disorders. In this review, I will provide an update of the structures of the A2A agonists known, their selectivity versus other adenosine receptors, and their latest therapeutic applications. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  8. Adaptive optics scanning laser ophthalmoscopy in fundus imaging, a review and update.

    PubMed

    Zhang, Bing; Li, Ni; Kang, Jie; He, Yi; Chen, Xiao-Ming

    2017-01-01

    Adaptive optics scanning laser ophthalmoscopy (AO-SLO) has been a promising technique in funds imaging with growing popularity. This review firstly gives a brief history of adaptive optics (AO) and AO-SLO. Then it compares AO-SLO with conventional imaging methods (fundus fluorescein angiography, fundus autofluorescence, indocyanine green angiography and optical coherence tomography) and other AO techniques (adaptive optics flood-illumination ophthalmoscopy and adaptive optics optical coherence tomography). Furthermore, an update of current research situation in AO-SLO is made based on different fundus structures as photoreceptors (cones and rods), fundus vessels, retinal pigment epithelium layer, retinal nerve fiber layer, ganglion cell layer and lamina cribrosa. Finally, this review indicates possible research directions of AO-SLO in future.

  9. Mapping Interaction Sites on Human Chemokine Receptors by Deep Mutational Scanning.

    PubMed

    Heredia, Jeremiah D; Park, Jihye; Brubaker, Riley J; Szymanski, Steven K; Gill, Kevin S; Procko, Erik

    2018-06-01

    Chemokine receptors CXCR4 and CCR5 regulate WBC trafficking and are engaged by the HIV-1 envelope glycoprotein gp120 during infection. We combine a selection of human CXCR4 and CCR5 libraries comprising nearly all of ∼7000 single amino acid substitutions with deep sequencing to define sequence-activity landscapes for surface expression and ligand interactions. After consideration of sequence constraints for surface expression, known interaction sites with HIV-1-blocking Abs were appropriately identified as conserved residues following library sorting for Ab binding, validating the use of deep mutational scanning to map functional interaction sites in G protein-coupled receptors. Chemokine CXCL12 was found to interact with residues extending asymmetrically into the CXCR4 ligand-binding cavity, similar to the binding surface of CXCR4 recognized by an antagonistic viral chemokine previously observed crystallographically. CXCR4 mutations distal from the chemokine binding site were identified that enhance chemokine recognition. This included disruptive mutations in the G protein-coupling site that diminished calcium mobilization, as well as conservative mutations to a membrane-exposed site (CXCR4 residues H79 2.45 and W161 4.50 ) that increased ligand binding without loss of signaling. Compared with CXCR4-CXCL12 interactions, CCR5 residues conserved for gp120 (HIV-1 BaL strain) interactions map to a more expansive surface, mimicking how the cognate chemokine CCL5 makes contacts across the entire CCR5 binding cavity. Acidic substitutions in the CCR5 N terminus and extracellular loops enhanced gp120 binding. This study demonstrates how comprehensive mutational scanning can define functional interaction sites on receptors, and novel mutations that enhance receptor activities can be found simultaneously. Copyright © 2018 by The American Association of Immunologists, Inc.

  10. An updated phylogenetic analysis of vertebrate melatonin receptor sequences: reflection on the melatonin receptor nomenclature by the Nomenclature Subcommittee of the International Union of Pharmacology.

    PubMed

    Shiu, S Y; Pang, S F

    1998-01-01

    In the past few years, significant progress on melatonin receptor research has led to the discovery of a family of genetically related but pharmacologically distinctive G-protein-coupled receptors in the vertebrates. With increasing number of receptor clones being identified, there is a need for a system of classification and nomenclature for these receptor subtypes. Recently, an updated nomenclature system, which has renamed the existing mammalian melatonin receptor clones, has been proposed by the relevant subcommittee of the International Union of Pharmacology (NC-IUPHAR). However, the majority of receptor clones which have been identified in non-mammalian vertebrates are not clearly defined by this system. By performing phylogenetic analysis of both mammalian and non-mammalian melatonin receptor clones, we would like to propose a classification-nomenclature system for vertebrate melatonin receptors. Hopefully, our system, which incorporates genetic data as well as the pharmacological criteria that have been adopted by the NC-IUPHAR nomenclature system, will provide the framework for future development of a unified scheme of classification and nomenclature for melatonin receptors.

  11. Adaptive optics scanning laser ophthalmoscopy in fundus imaging, a review and update

    PubMed Central

    Zhang, Bing; Li, Ni; Kang, Jie; He, Yi; Chen, Xiao-Ming

    2017-01-01

    Adaptive optics scanning laser ophthalmoscopy (AO-SLO) has been a promising technique in funds imaging with growing popularity. This review firstly gives a brief history of adaptive optics (AO) and AO-SLO. Then it compares AO-SLO with conventional imaging methods (fundus fluorescein angiography, fundus autofluorescence, indocyanine green angiography and optical coherence tomography) and other AO techniques (adaptive optics flood-illumination ophthalmoscopy and adaptive optics optical coherence tomography). Furthermore, an update of current research situation in AO-SLO is made based on different fundus structures as photoreceptors (cones and rods), fundus vessels, retinal pigment epithelium layer, retinal nerve fiber layer, ganglion cell layer and lamina cribrosa. Finally, this review indicates possible research directions of AO-SLO in future. PMID:29181321

  12. Update of the androgen receptor gene mutations database.

    PubMed

    Gottlieb, B; Beitel, L K; Lumbroso, R; Pinsky, L; Trifiro, M

    1999-01-01

    The current version of the androgen receptor (AR) gene mutations database is described. The total number of reported mutations has risen from 309 to 374 during the past year. We have expanded the database by adding information on AR-interacting proteins; and we have improved the database by identifying those mutation entries that have been updated. Mutations of unknown significance have now been reported in both the 5' and 3' untranslated regions of the AR gene, and in individuals who are somatic mosaics constitutionally. In addition, single nucleotide polymorphisms, including silent mutations, have been discovered in normal individuals and in individuals with male infertility. A mutation hotspot associated with prostatic cancer has been identified in exon 5. The database is available on the internet (http://www.mcgill.ca/androgendb/), from EMBL-European Bioinformatics Institute (ftp.ebi.ac.uk/pub/databases/androgen), or as a Macintosh FilemakerPro or Word file (MC33@musica.mcgill.ca). Copyright 1999 Wiley-Liss, Inc.

  13. Laser Scanning Cytometry: Principles and Applications—An Update

    PubMed Central

    Pozarowski, Piotr; Holden, Elena; Darzynkiewicz, Zbigniew

    2012-01-01

    Laser scanning cytometer (LSC) is the microscope-based cytofluorometer that offers a plethora of unique analytical capabilities, not provided by flow cytometry (FCM). This review describes attributes of LSC and covers its numerous applications derived from plentitude of the parameters that can be measured. Among many LSC applications the following are emphasized: (a) assessment of chromatin condensation to identify mitotic, apoptotic cells, or senescent cells; (b) detection of nuclear or mitochondrial translocation of critical factors such as NF-κB, p53, or Bax; (c) semi-automatic scoring of micronuclei in mutagenicity assays; (d) analysis of fluorescence in situ hybridization (FISH) and use of the FISH analysis attribute to measure other punctuate fluorescence patterns such as γH2AX foci or receptor clustering; (e) enumeration and morphometry of nucleoli and other cell organelles; (f) analysis of progeny of individual cells in clonogenicity assay; (g) cell immunophenotyping; (h) imaging, visual examination, or sequential analysis using different probes of the same cells upon their relocation; (i) in situ enzyme kinetics, drug uptake, and other time-resolved processes; (j) analysis of tissue section architecture using fluorescent and chromogenic probes; (k) application for hypocellular samples (needle aspirate, spinal fluid, etc.); and (l) other clinical applications. Advantages and limitations of LSC are discussed and compared with FCM. PMID:23027005

  14. The UCL low-density lipoprotein receptor gene variant database: pathogenicity update

    PubMed Central

    Futema, Marta; Whittall, Ros; Taylor-Beadling, Alison; Williams, Maggie; den Dunnen, Johan T; Humphries, Steve E

    2017-01-01

    Background Familial hypercholesterolaemia (OMIM 143890) is most frequently caused by variations in the low-density lipoprotein receptor (LDLR) gene. Predicting whether novel variants are pathogenic may not be straightforward, especially for missense and synonymous variants. In 2013, the Association of Clinical Genetic Scientists published guidelines for the classification of variants, with categories 1 and 2 representing clearly not or unlikely pathogenic, respectively, 3 representing variants of unknown significance (VUS), and 4 and 5 representing likely to be or clearly pathogenic, respectively. Here, we update the University College London (UCL) LDLR variant database according to these guidelines. Methods PubMed searches and alerts were used to identify novel LDLR variants for inclusion in the database. Standard in silico tools were used to predict potential pathogenicity. Variants were designated as class 4/5 only when the predictions from the different programs were concordant and as class 3 when predictions were discordant. Results The updated database (http://www.lovd.nl/LDLR) now includes 2925 curated variants, representing 1707 independent events. All 129 nonsense variants, 337 small frame-shifting and 117/118 large rearrangements were classified as 4 or 5. Of the 795 missense variants, 115 were in classes 1 and 2, 605 in class 4 and 75 in class 3. 111/181 intronic variants, 4/34 synonymous variants and 14/37 promoter variants were assigned to classes 4 or 5. Overall, 112 (7%) of reported variants were class 3. Conclusions This study updates the LDLR variant database and identifies a number of reported VUS where additional family and in vitro studies will be required to confirm or refute their pathogenicity. PMID:27821657

  15. International Union of Pharmacology. LXXXIX. Update on the Extended Family of Chemokine Receptors and Introducing a New Nomenclature for Atypical Chemokine Receptors

    PubMed Central

    Bachelerie, Francoise; Ben-Baruch, Adit; Burkhardt, Amanda M.; Combadiere, Christophe; Farber, Joshua M.; Graham, Gerard J.; Horuk, Richard; Sparre-Ulrich, Alexander Hovard; Locati, Massimo; Luster, Andrew D.; Mantovani, Alberto; Matsushima, Kouji; Nibbs, Robert; Nomiyama, Hisayuki; Power, Christine A.; Proudfoot, Amanda E. I.; Rosenkilde, Mette M.; Rot, Antal; Sozzani, Silvano; Thelen, Marcus; Yoshie, Osamu; Zlotnik, Albert

    2014-01-01

    Sixteen years ago, the Nomenclature Committee of the International Union of Pharmacology approved a system for naming human seven-transmembrane (7TM) G protein-coupled chemokine receptors, the large family of leukocyte chemoattractant receptors that regulates immune system development and function, in large part by mediating leukocyte trafficking. This was announced in Pharmacological Reviews in a major overview of the first decade of research in this field [Murphy PM, Baggiolini M, Charo IF, Hébert CA, Horuk R, Matsushima K, Miller LH, Oppenheim JJ, and Power CA (2000) Pharmacol Rev 52:145–176]. Since then, several new receptors have been discovered, and major advances have been made for the others in many areas, including structural biology, signal transduction mechanisms, biology, and pharmacology. New and diverse roles have been identified in infection, immunity, inflammation, development, cancer, and other areas. The first two drugs acting at chemokine receptors have been approved by the U.S. Food and Drug Administration (FDA), maraviroc targeting CCR5 in human immunodeficiency virus (HIV)/AIDS, and plerixafor targeting CXCR4 for stem cell mobilization for transplantation in cancer, and other candidates are now undergoing pivotal clinical trials for diverse disease indications. In addition, a subfamily of atypical chemokine receptors has emerged that may signal through arrestins instead of G proteins to act as chemokine scavengers, and many microbial and invertebrate G protein-coupled chemokine receptors and soluble chemokine-binding proteins have been described. Here, we review this extended family of chemokine receptors and chemokine-binding proteins at the basic, translational, and clinical levels, including an update on drug development. We also introduce a new nomenclature for atypical chemokine receptors with the stem ACKR (atypical chemokine receptor) approved by the Nomenclature Committee of the International Union of Pharmacology and the Human

  16. Epidermal growth factor receptor subunit locations determined in hydrated cells with environmental scanning electron microscopy.

    PubMed

    Peckys, Diana B; Baudoin, Jean-Pierre; Eder, Magdalena; Werner, Ulf; de Jonge, Niels

    2013-01-01

    Imaging single epidermal growth factor receptors (EGFR) in intact cells is presently limited by the available microscopy methods. Environmental scanning electron microscopy (ESEM) of whole cells in hydrated state in combination with specific labeling with gold nanoparticles was used to localize activated EGFRs in the plasma membranes of COS7 and A549 cells. The use of a scanning transmission electron microscopy (STEM) detector yielded a spatial resolution of 3 nm, sufficient to identify the locations of individual EGFR dimer subunits. The sizes and distribution of dimers and higher order clusters of EGFRs were determined. The distance between labels bound to dimers amounted to 19 nm, consistent with a molecular model. A fraction of the EGFRs was found in higher order clusters with sizes ranging from 32-56 nm. ESEM can be used for quantitative whole cell screening studies of membrane receptors, and for the study of nanoparticle-cell interactions in general.

  17. Epidermal growth factor receptor subunit locations determined in hydrated cells with environmental scanning electron microscopy

    PubMed Central

    Peckys, Diana B.; Baudoin, Jean-Pierre; Eder, Magdalena; Werner, Ulf; de Jonge, Niels

    2013-01-01

    Imaging single epidermal growth factor receptors (EGFR) in intact cells is presently limited by the available microscopy methods. Environmental scanning electron microscopy (ESEM) of whole cells in hydrated state in combination with specific labeling with gold nanoparticles was used to localize activated EGFRs in the plasma membranes of COS7 and A549 cells. The use of a scanning transmission electron microscopy (STEM) detector yielded a spatial resolution of 3 nm, sufficient to identify the locations of individual EGFR dimer subunits. The sizes and distribution of dimers and higher order clusters of EGFRs were determined. The distance between labels bound to dimers amounted to 19 nm, consistent with a molecular model. A fraction of the EGFRs was found in higher order clusters with sizes ranging from 32–56 nm. ESEM can be used for quantitative whole cell screening studies of membrane receptors, and for the study of nanoparticle-cell interactions in general. PMID:24022088

  18. Functioning of the dimeric GABAB receptor extracellular domain revealed by glycan wedge scanning

    PubMed Central

    Rondard, Philippe; Huang, Siluo; Monnier, Carine; Tu, Haijun; Blanchard, Bertrand; Oueslati, Nadia; Malhaire, Fanny; Li, Ying; Trinquet, Eric; Labesse, Gilles; Pin, Jean-Philippe; Liu, Jianfeng

    2008-01-01

    The G-protein-coupled receptor (GPCR) activated by the neurotransmitter GABA is made up of two subunits, GABAB1 and GABAB2. GABAB1 binds agonists, whereas GABAB2 is required for trafficking GABAB1 to the cell surface, increasing agonist affinity to GABAB1, and activating associated G proteins. These subunits each comprise two domains, a Venus flytrap domain (VFT) and a heptahelical transmembrane domain (7TM). How agonist binding to the GABAB1 VFT leads to GABAB2 7TM activation remains unknown. Here, we used a glycan wedge scanning approach to investigate how the GABAB VFT dimer controls receptor activity. We first identified the dimerization interface using a bioinformatics approach and then showed that introducing an N-glycan at this interface prevents the association of the two subunits and abolishes all activities of GABAB2, including agonist activation of the G protein. We also identified a second region in the VFT where insertion of an N-glycan does not prevent dimerization, but blocks agonist activation of the receptor. These data provide new insight into the function of this prototypical GPCR and demonstrate that a change in the dimerization interface is required for receptor activation. PMID:18388862

  19. Pulmonary ventilation/perfusion scan

    MedlinePlus

    ... take a ventilation and perfusion scan and then evaluate it with a chest x-ray. All parts ... ADAM Health Solutions. About MedlinePlus Site Map FAQs Customer Support Get email updates Subscribe to RSS Follow ...

  20. Application of terrestrial laser scanning to the development and updating of the base map

    NASA Astrophysics Data System (ADS)

    Klapa, Przemysław; Mitka, Bartosz

    2017-06-01

    The base map provides basic information about land to individuals, companies, developers, design engineers, organizations, and government agencies. Its contents include spatial location data for control network points, buildings, land lots, infrastructure facilities, and topographic features. As the primary map of the country, it must be developed in accordance with specific laws and regulations and be continuously updated. The base map is a data source used for the development and updating of derivative maps and other large scale cartographic materials such as thematic or topographic maps. Thanks to the advancement of science and technology, the quality of land surveys carried out by means of terrestrial laser scanning (TLS) matches that of traditional surveying methods in many respects. This paper discusses the potential application of output data from laser scanners (point clouds) to the development and updating of cartographic materials, taking Poland's base map as an example. A few research sites were chosen to present the method and the process of conducting a TLS land survey: a fragment of a residential area, a street, the surroundings of buildings, and an undeveloped area. The entire map that was drawn as a result of the survey was checked by comparing it to a map obtained from PODGiK (pol. Powiatowy Ośrodek Dokumentacji Geodezyjnej i Kartograficznej - Regional Centre for Geodetic and Cartographic Records) and by conducting a field inspection. An accuracy and quality analysis of the conducted fieldwork and deskwork yielded very good results, which provide solid grounds for predicating that cartographic materials based on a TLS point cloud are a reliable source of information about land. The contents of the map that had been created with the use of the obtained point cloud were very accurately located in space (x, y, z). The conducted accuracy analysis and the inspection of the performed works showed that high quality is characteristic of TLS surveys. The

  1. Translational repression of mouse mu opioid receptor expression via leaky scanning

    PubMed Central

    Song, Kyu Young; Hwang, Cheol Kyu; Kim, Chun Sung; Choi, Hack Sun; Law, Ping-Yee; Wei, Li-Na; Loh, Horace H.

    2007-01-01

    Mu opioid receptor (MOR) expression is under temporal and spatial controls, but expression levels of the MOR gene are relatively low in vivo. In addition to transcriptional regulations, upstream AUGs (uAUGs) and open reading frames (uORFs) profoundly affect the translation of the primary ORF and thus the protein levels in several genes. The 5′-untranslated region (UTR) of mouse MOR mRNA contains three uORFs preceding the MOR main initiation codon. In MOR-fused EGFP or MOR promoter/luciferase reporter constructs, mutating each uAUG individually or in combinations increased MOR transient heterologous expression in neuroblastoma NMB and HEK293 cells significantly. Translation of such constructs increased up to 3-fold without altering the mRNA levels if either the third uAUG or both the second and third AUGs were mutated. Additionally, these uAUG-mediated translational inhibitions were independent of their peptide as confirmed by internal mutation analyses in each uORF. Translational studies indicated that protein syntheses were initiated at these uAUG initiation sites, with the third uAUG initiating the highest translation level. These results support the hypothesis that uORFs in mouse MOR mRNA act as negative regulators through a ribosome leaky scanning mechanism. Such leaky scanning resulted in the suppression of mouse MOR under normal conditions. PMID:17284463

  2. Dual-color dual-focus line-scanning FCS for quantitative analysis of receptor-ligand interactions in living specimens.

    PubMed

    Dörlich, René M; Chen, Qing; Niklas Hedde, Per; Schuster, Vittoria; Hippler, Marc; Wesslowski, Janine; Davidson, Gary; Nienhaus, G Ulrich

    2015-05-07

    Cellular communication in multi-cellular organisms is mediated to a large extent by a multitude of cell-surface receptors that bind specific ligands. An in-depth understanding of cell signaling networks requires quantitative information on ligand-receptor interactions within living systems. In principle, fluorescence correlation spectroscopy (FCS) based methods can provide such data, but live-cell applications have proven extremely challenging. Here, we have developed an integrated dual-color dual-focus line-scanning fluorescence correlation spectroscopy (2c2f lsFCS) technique that greatly facilitates live-cell and tissue experiments. Absolute ligand and receptor concentrations and their diffusion coefficients within the cell membrane can be quantified without the need to perform additional calibration experiments. We also determine the concentration of ligands diffusing in the medium outside the cell within the same experiment by using a raster image correlation spectroscopy (RICS) based analysis. We have applied this robust technique to study the interactions of two Wnt antagonists, Dickkopf1 and Dickkopf2 (Dkk1/2), to their cognate receptor, low-density-lipoprotein-receptor related protein 6 (LRP6), in the plasma membrane of living HEK293T cells. We obtained significantly lower affinities than previously reported using in vitro studies, underscoring the need to measure such data on living cells or tissues.

  3. NMDA receptor modulators: an updated patent review (2013-2014).

    PubMed

    Strong, Katie L; Jing, Yao; Prosser, Anthony R; Traynelis, Stephen F; Liotta, Dennis C

    2014-12-01

    The NMDA receptor mediates a slow component of excitatory synaptic transmission, and NMDA receptor dysfunction has been implicated in numerous neurological disorders. Thus, interest in developing modulators that are capable of regulating the channel continues to be strong. Recent research has led to the discovery of a number of compounds that hold therapeutic and clinical value. Deeper insight into the NMDA intersubunit interactions and structural motifs gleaned from the recently solved crystal structures of the NMDA receptor should facilitate a deeper understanding of how these compounds modulate the receptor. This article discusses the known pharmacology of NMDA receptors. A discussion of the patent literature since 2012 is also included, with an emphasis on those that claimed new chemical entities as regulators of the NMDA receptor. The number of patents involving novel NMDA receptor modulators suggests a renewed interest in the NMDA receptor as a therapeutic target. Subunit-selective modulators continue to show promise, and the development of new subunit-selective NMDA receptor modulators appears poised for continued growth. Although a modest number of channel blocker patents were published, successful clinical outcomes involving ketamine have led to a resurgent interest in low-affinity channel blockers as therapeutics.

  4. Visual Scanning Training For Older Drivers: A Literature Review

    DOT National Transportation Integrated Search

    2018-04-01

    This literature review focuses on older drivers' visual scanning ability and on evaluations of training in visual scanning skills for older adults, updating a previous review of studies published from 1997 to 2008 describing age-related functional ch...

  5. The scanning model for translation: an update

    PubMed Central

    1989-01-01

    The small (40S) subunit of eukaryotic ribosomes is believed to bind initially at the capped 5'-end of messenger RNA and then migrate, stopping at the first AUG codon in a favorable context for initiating translation. The first-AUG rule is not absolute, but there are rules for breaking the rule. Some anomalous observations that seemed to contradict the scanning mechanism now appear to be artifacts. A few genuine anomalies remain unexplained. PMID:2645293

  6. Measurement of density and affinity for dopamine D2 receptors by a single positron emission tomography scan with multiple injections of [11C]raclopride

    PubMed Central

    Ikoma, Yoko; Watabe, Hiroshi; Hayashi, Takuya; Miyake, Yoshinori; Teramoto, Noboru; Minato, Kotaro; Iida, Hidehiro

    2010-01-01

    Positron emission tomography (PET) with [11C]raclopride has been used to investigate the density (Bmax) and affinity (Kd) of dopamine D2 receptors related to several neurological and psychiatric disorders. However, in assessing the Bmax and Kd, multiple PET scans are necessary under variable specific activities of administered [11C]raclopride, resulting in a long study period and unexpected physiological variations. In this paper, we have developed a method of multiple-injection graphical analysis (MI-GA) that provides the Bmax and Kd values from a single PET scan with three sequential injections of [11C]raclopride, and we validated the proposed method by performing numerous simulations and PET studies on monkeys. In the simulations, the three-injection protocol was designed according to prior knowledge of the receptor kinetics, and the errors of Bmax and Kd estimated by MI-GA were analyzed. Simulations showed that our method could support the calculation of Bmax and Kd, despite a slight overestimation compared with the true magnitudes. In monkey studies, we could calculate the Bmax and Kd of diseased or normal striatum in a 150 mins scan with the three-injection protocol of [11C]raclopride. Estimated Bmax and Kd values of D2 receptors in normal or partially dopamine-depleted striatum were comparable to the previously reported values. PMID:19904285

  7. Antiemetics: American Society of Clinical Oncology Clinical Practice Guideline Update

    PubMed Central

    Basch, Ethan; Prestrud, Ann Alexis; Hesketh, Paul J.; Kris, Mark G.; Feyer, Petra C.; Somerfield, Mark R.; Chesney, Maurice; Clark-Snow, Rebecca Anne; Flaherty, Anne Marie; Freundlich, Barbara; Morrow, Gary; Rao, Kamakshi V.; Schwartz,, Rowena N.; Lyman, Gary H.

    2011-01-01

    Purpose To update the American Society of Clinical Oncology (ASCO) guideline for antiemetics in oncology. Methods A systematic review of the medical literature was completed to inform this update. MEDLINE, the Cochrane Collaboration Library, and meeting materials from ASCO and the Multinational Association for Supportive Care in Cancer were all searched. Primary outcomes of interest were complete response and rates of any vomiting or nausea. Results Thirty-seven trials met prespecified inclusion and exclusion criteria for this systematic review. Two systematic reviews from the Cochrane Collaboration were identified; one surveyed the pediatric literature. The other compared the relative efficacy of the 5-hydroxytryptamine-3 (5-HT3) receptor antagonists. Recommendations Combined anthracycline and cyclophosphamide regimens were reclassified as highly emetic. Patients who receive this combination or any highly emetic agents should receive a 5-HT3 receptor antagonist, dexamethasone, and a neurokinin 1 (NK1) receptor antagonist. A large trial validated the equivalency of fosaprepitant, a single-day intravenous formulation, with aprepitant; either therapy is appropriate. Preferential use of palonosetron is recommended for moderate emetic risk regimens, combined with dexamethasone. For low-risk agents, patients can be offered dexamethasone before the first dose of chemotherapy. Patients undergoing high emetic risk radiation therapy should receive a 5-HT3 receptor antagonist before each fraction and for 24 hours after treatment and may receive a 5-day course of dexamethasone during fractions 1 to 5. The Update Committee noted the importance of continued symptom monitoring throughout therapy. Clinicians underestimate the incidence of nausea, which is not as well controlled as emesis. PMID:21947834

  8. Comparative Geometrical Accuracy Investigations of Hand-Held 3d Scanning Systems - AN Update

    NASA Astrophysics Data System (ADS)

    Kersten, T. P.; Lindstaedt, M.; Starosta, D.

    2018-05-01

    Hand-held 3D scanning systems are increasingly available on the market from several system manufacturers. These systems are deployed for 3D recording of objects with different size in diverse applications, such as industrial reverse engineering, and documentation of museum exhibits etc. Typical measurement distances range from 0.5 m to 4.5 m. Although they are often easy-to-use, the geometric performance of these systems, especially the precision and accuracy, are not well known to many users. First geometrical investigations of a variety of diverse hand-held 3D scanning systems were already carried out by the Photogrammetry & Laser Scanning Lab of the HafenCity University Hamburg (HCU Hamburg) in cooperation with two other universities in 2016. To obtain more information about the accuracy behaviour of the latest generation of hand-held 3D scanning systems, HCU Hamburg conducted further comparative geometrical investigations using structured light systems with speckle pattern (Artec Spider, Mantis Vision PocketScan 3D, Mantis Vision F5-SR, Mantis Vision F5-B, and Mantis Vision F6), and photogrammetric systems (Creaform HandySCAN 700 and Shining FreeScan X7). In the framework of these comparative investigations geometrically stable reference bodies were used. The appropriate reference data was acquired by measurements with two structured light projection systems (AICON smartSCAN and GOM ATOS I 2M). The comprehensive test results of the different test scenarios are presented and critically discussed in this contribution.

  9. TRMM Microwave Imager (TMI) Updates for Final Data Version Release

    NASA Technical Reports Server (NTRS)

    Kroodsma, Rachael A; Bilanow, Stephen; Ji, Yimin; McKague, Darren

    2017-01-01

    The Tropical Rainfall Measuring Mission (TRMM) Microwave Imager (TMI) dataset released by the Precipitation Processing System (PPS) will be updated to a final version within the next year. These updates are based on increased knowledge in recent years of radiometer calibration and sensor performance issues. In particular, the Global Precipitation Measurement (GPM) Microwave Imager (GMI) is used as a model for many of the TMI version updates. This paper discusses four aspects of the TMI data product that will be improved: spacecraft attitude, calibration and quality control, along-scan bias corrections, and sensor pointing accuracy. These updates will be incorporated into the final TMI data version, improving the quality of the data product and ensuring accurate geophysical parameters can be derived from TMI.

  10. Lidar - ND Halo Scanning Doppler, Boardman - Reviewed Data

    DOE Data Explorer

    Otarola, Sebastian

    2017-10-23

    The University of Notre Dame (ND) scanning LiDAR dataset used for the WFIP2 Campaign is provided. The LiDAR is a Halo Photonics Stream Line Scanning Doppler LiDAR. **It is highly recommended to discuss any planned use of these data with University of Notre Dame scientists**. For more information refer to Section 4.c) in the updated version of the "WFIP2 Project (lidar.z07)" Readme file, where the lidar.z07.b0 dataset is fully explained.

  11. Spatial updating in human parietal cortex

    NASA Technical Reports Server (NTRS)

    Merriam, Elisha P.; Genovese, Christopher R.; Colby, Carol L.

    2003-01-01

    Single neurons in monkey parietal cortex update visual information in conjunction with eye movements. This remapping of stimulus representations is thought to contribute to spatial constancy. We hypothesized that a similar process occurs in human parietal cortex and that we could visualize it with functional MRI. We scanned subjects during a task that involved remapping of visual signals across hemifields. We observed an initial response in the hemisphere contralateral to the visual stimulus, followed by a remapped response in the hemisphere ipsilateral to the stimulus. We ruled out the possibility that this remapped response resulted from either eye movements or visual stimuli alone. Our results demonstrate that updating of visual information occurs in human parietal cortex.

  12. The use of portable intraoperative computed tomography scanning for real-time image guidance: a pilot cadaver study.

    PubMed

    Das, Subinoy; Maeso, Patricia A; Figueroa, Ramon E; Senior, Brent A; Delgaudio, John M; Sillers, Michael J; Schlosser, Rod J; Kountakis, Stilianos E

    2008-01-01

    This study was performed to assess the feasibility of using intraoperative computed tomography (CT) to provide real-time updates to image guidance systems (IGSs) during surgery. The xCAT ENT portable intraoperative CT scanner (Xoran Technologies, Ann Arbor, MI) was used to acquire scans before, midway, and at the end of six cadaver dissections during the Southern States Rhinology Course, Augusta, GA, in October 2006. These scans were used to recalibrate three different IGSs used during the dissection. Time measurements were recorded and dosimetry was obtained from the cornea, sphenoid sinus (near the optic chiasm), and from the operative field during acquisition of the images. IGS accuracy was determined at the skull base and lamina papyracea. Surgeons were interviewed on benefits of real-time updates to the IGS after completion of dissections. The xCAT ENT scanner was compatible with all three IGS platforms. The average time to update the IGS was 13 minutes. Radiation doses to the cornea were 620 mrad per scan, and optic chiasm was 800 mrad/scan. The accuracy at the anterior skull base improved from 1.58 to 0.62 mm (p=0.026). The accuracy at the posterior skull base improved from 1.46 to 0.71 mm (p=0.014). The accuracy at the lamina was not significantly changed. Intraoperative portable CT scanning with real-time IGS updates is feasible and likely would add little additional time. Accuracy is improved at the skull base. Prospective studies on actual patients are warranted.

  13. Estrogen receptor ligands: a patent review update.

    PubMed

    Paterni, Ilaria; Bertini, Simone; Granchi, Carlotta; Macchia, Marco; Minutolo, Filippo

    2013-10-01

    The role of estrogens is mostly mediated by two nuclear receptors (ERα and ERβ) and a membrane-associated G-protein (GPR30 or GPER), and it is not limited to reproduction, but it extends to the skeletal, cardiovascular and central nervous systems. Various pathologies such as cancer, inflammatory, neurodegenerative and metabolic diseases are often associated with dysfunctions of the estrogenic system. Therapeutic interventions by agents that affect the estrogenic signaling pathway might be useful in the treatment of many dissimilar diseases. The massive chemodiversity of ER ligands, limited to patented small molecules, is herein reviewed. The reported compounds are classified on the basis of their chemical structures. Non-steroidal derivatives, which mostly consist of diphenolic compounds, are further segregated into chemical classes based on their central scaffold. Estrogens have been used for almost a century and their earlier applications have concerned interventions in the female reproductive functions, as well as the treatment of some estrogen-dependent cancers and osteoporosis. Since the discovery of ERβ in 1996, the patent literature has started to pay a progressively increasing attention to this newer receptor subtype, which holds promise as a target for new indications, most of which still need to be clinically validated.

  14. Verification and Updating of the Database of Topographic Objects with Geometric Information About Buildings by Means of Airborne Laser Scanning Data

    NASA Astrophysics Data System (ADS)

    Mendela-Anzlik, Małgorzata; Borkowski, Andrzej

    2017-06-01

    Airborne laser scanning data (ALS) are used mainly for creation of precise digital elevation models. However, it appears that the informative potential stored in ALS data can be also used for updating spatial databases, including the Database of Topographic Objects (BDOT10k). Typically, geometric representations of buildings in the BDOT10k are equal to their entities in the Land and Property Register (EGiB). In this study ALS is considered as supporting data source. The thresholding method of original ALS data with the use of the alpha shape algorithm, proposed in this paper, allows for extraction of points that represent horizontal cross section of building walls, leading to creation of vector, geometric models of buildings that can be then used for updating the BDOT10k. This method gives also the possibility of an easy verification of up-to-dateness of both the BDOT10k and the district EGiB databases within geometric information about buildings. For verification of the proposed methodology there have been used the classified ALS data acquired with a density of 4 points/m2. The accuracy assessment of the identified building outlines has been carried out by their comparison to the corresponding EGiB objects. The RMSE values for 78 buildings are from a few to tens of centimeters and the average value is about 0,5 m. At the same time for several objects there have been revealed huge geometric discrepancies. Further analyses have shown that these discrepancies could be resulted from incorrect representations of buildings in the EGiB database.

  15. Selective updating of working memory content modulates meso-cortico-striatal activity.

    PubMed

    Murty, Vishnu P; Sambataro, Fabio; Radulescu, Eugenia; Altamura, Mario; Iudicello, Jennifer; Zoltick, Bradley; Weinberger, Daniel R; Goldberg, Terry E; Mattay, Venkata S

    2011-08-01

    Accumulating evidence from non-human primates and computational modeling suggests that dopaminergic signals arising from the midbrain (substantia nigra/ventral tegmental area) mediate striatal gating of the prefrontal cortex during the selective updating of working memory. Using event-related functional magnetic resonance imaging, we explored the neural mechanisms underlying the selective updating of information stored in working memory. Participants were scanned during a novel working memory task that parses the neurophysiology underlying working memory maintenance, overwriting, and selective updating. Analyses revealed a functionally coupled network consisting of a midbrain region encompassing the substantia nigra/ventral tegmental area, caudate, and dorsolateral prefrontal cortex that was selectively engaged during working memory updating compared to the overwriting and maintenance of working memory content. Further analysis revealed differential midbrain-dorsolateral prefrontal interactions during selective updating between low-performing and high-performing individuals. These findings highlight the role of this meso-cortico-striatal circuitry during the selective updating of working memory in humans, which complements previous research in behavioral neuroscience and computational modeling. Published by Elsevier Inc.

  16. Breast cancer: updates and advances in 2016.

    PubMed

    Giordano, Sara B; Gradishar, William

    2017-02-01

    Approximately 1 in 8 US women (12%) will develop invasive breast cancer over the course of her lifetime. In 2016, an estimated 246,660 new cases of invasive breast cancer are expected to be diagnosed and approximately 40,450 would die as a result of it. The global burden of breast cancer exceeds all other cancers and the incidence is increasing. The heterogeneity of breast cancer makes it a challenging solid tumor to diagnose and treat. This review focuses on the recent advances in breast cancer therapy including hormonal treatment of metastatic breast cancer, targeting cyclin-dependent kinases (CDK) 4/6 in breast cancer, updates in targeting human epidermal growth factor receptor 2 (HER2) positive breast cancer, adaptive randomization trial design and cancer genetic risk assessment. Breast cancer is a heterogeneous disease and targeted therapy is improving the outcomes of women. The use of cyclin-dependent kinase inhibitors (CDK) 4/6 have demonstrated a substantial improvement in progression-free survival in the first line setting of metastatic hormone receptor positive breast cancer. And newer agents directed at HER2 continue to revolutionize HER2-positive breast cancer treatment. This review highlights the recent updates in breast cancer treatment, new concepts in clinical trial design and provides a current overview of cancer genetic risk assessment.

  17. Breast and gastrointestinal cancer updates from ASCO 2015.

    PubMed

    Dawood, Shaheenah

    2015-01-01

    This review focuses on the updates presented at the ASCO 2015 symposium in breast and gastrointestinal malignancies. Some were practice changing while others gave us an exciting glimpse into what's to come in the very near future. Immunotherapy was the buzz word this year with data presented on every tumor site. Data on the efficacy of anti PD-1 agents in colorectal, hepatocellular and gastric cancer were presented. In breast cancer we saw data on a new and exciting therapeutic target in the form of androgen receptor among triple receptor negative breast tumors presented. Positive results of the PALOMA 3 trial were presented that has given women with hormone receptor positive metastatic breast cancer another therapeutic option. Furthermore data on strategies to further improve anti her2 therapy, optimizing of chemotherapy in the early and advanced stage and various strategies to improve endocrine therapy among patients with breast cancer were presented.

  18. The role of 5 HT6-receptor antagonists in Alzheimer's disease: an update.

    PubMed

    Khoury, Rita; Grysman, Noam; Gold, Jake; Patel, Kush; Grossberg, George T

    2018-06-01

    Despite recent advances in Alzheimer's disease (AD) research, no breakthrough treatments have been discovered. Cholinesterase inhibitors and the NMDA-receptor antagonist memantine are currently the two approved symptomatic treatments for AD. 5-HT6 receptor antagonism has recently emerged as a promising treatment strategy to improve cognition in AD, with a modest side-effect profile. Areas covered: 5-HT6 receptors, exclusively found in the central nervous system, modulate primarily GABA and glutamate levels, facilitating the secondary release of other neurotransmitters including dopamine, noradrenaline, and acetylcholine, all of which are compromised in AD. This review discusses findings of preclinical and phase I-III clinical trials conducted with three major 5-HT6 receptor antagonists: idalopirdine, intepirdine, and SUVN-502, in the field of AD. Expert opinion: Despite early positive findings, larger phase-III trials have failed to demonstrate any statistically significant impact on cognition for both idalopirdine and intepirdine, as adjunct to cholinesterase inhibitors. Paradoxically, 5-HT6 receptor agonists have also been shown to have cognitive enhancing properties. Thus, a better understanding of the mechanism of action of the 5-HT6 receptor and its ligands is warranted. Investigating 5-HT6 receptor partial or inverse agonists may be promising in future AD trials.

  19. The G protein-coupled receptors deorphanization landscape.

    PubMed

    Laschet, Céline; Dupuis, Nadine; Hanson, Julien

    2018-07-01

    G protein-coupled receptors (GPCRs) are usually highlighted as being both the largest family of membrane proteins and the most productive source of drug targets. However, most of the GPCRs are understudied and hence cannot be used immediately for innovative therapeutic strategies. Besides, there are still around 100 orphan receptors, with no described endogenous ligand and no clearly defined function. The race to discover new ligands for these elusive receptors seems to be less intense than before. Here, we present an update of the various strategies employed to assign a function to these receptors and to discover new ligands. We focus on the recent advances in the identification of endogenous ligands with a detailed description of newly deorphanized receptors. Replication being a key parameter in these endeavors, we also discuss the latest controversies about problematic ligand-receptor pairings. In this context, we propose several recommendations in order to strengthen the reporting of new ligand-receptor pairs. Copyright © 2018 Elsevier Inc. All rights reserved.

  20. Dopamine receptors – IUPHAR Review 13

    PubMed Central

    Beaulieu, Jean-Martin; Espinoza, Stefano; Gainetdinov, Raul R

    2015-01-01

    The variety of physiological functions controlled by dopamine in the brain and periphery is mediated by the D1, D2, D3, D4 and D5 dopamine GPCRs. Drugs acting on dopamine receptors are significant tools for the management of several neuropsychiatric disorders including schizophrenia, bipolar disorder, depression and Parkinson's disease. Recent investigations of dopamine receptor signalling have shown that dopamine receptors, apart from their canonical action on cAMP-mediated signalling, can regulate a myriad of cellular responses to fine-tune the expression of dopamine-associated behaviours and functions. Such signalling mechanisms may involve alternate G protein coupling or non-G protein mechanisms involving ion channels, receptor tyrosine kinases or proteins such as β-arrestins that are classically involved in GPCR desensitization. Another level of complexity is the growing appreciation of the physiological roles played by dopamine receptor heteromers. Applications of new in vivo techniques have significantly furthered the understanding of the physiological functions played by dopamine receptors. Here we provide an update of the current knowledge regarding the complex biology, signalling, physiology and pharmacology of dopamine receptors. PMID:25671228

  1. Integrin traffic - the update.

    PubMed

    De Franceschi, Nicola; Hamidi, Hellyeh; Alanko, Jonna; Sahgal, Pranshu; Ivaska, Johanna

    2015-03-01

    Integrins are a family of transmembrane cell surface molecules that constitute the principal adhesion receptors for the extracellular matrix (ECM) and are indispensable for the existence of multicellular organisms. In vertebrates, 24 different integrin heterodimers exist with differing substrate specificity and tissue expression. Integrin-extracellular-ligand interaction provides a physical anchor for the cell and triggers a vast array of intracellular signalling events that determine cell fate. Dynamic remodelling of adhesions, through rapid endocytic and exocytic trafficking of integrin receptors, is an important mechanism employed by cells to regulate integrin-ECM interactions, and thus cellular signalling, during processes such as cell migration, invasion and cytokinesis. The initial concept of integrin traffic as a means to translocate adhesion receptors within the cell has now been expanded with the growing appreciation that traffic is intimately linked to the cell signalling apparatus. Furthermore, endosomal pathways are emerging as crucial regulators of integrin stability and expression in cells. Thus, integrin traffic is relevant in a number of pathological conditions, especially in cancer. Nearly a decade ago we wrote a Commentary in Journal of Cell Science entitled 'Integrin traffic'. With the advances in the field, we felt it would be appropriate to provide the growing number of researchers interested in integrin traffic with an update. © 2015. Published by The Company of Biologists Ltd.

  2. Automated Image Analysis Corrosion Working Group Update: February 1, 2018

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Wendelberger, James G.

    These are slides for the automated image analysis corrosion working group update. The overall goals were: automate the detection and quantification of features in images (faster, more accurate), how to do this (obtain data, analyze data), focus on Laser Scanning Confocal Microscope (LCM) data (laser intensity, laser height/depth, optical RGB, optical plus laser RGB).

  3. The dopamine D2 receptor antagonist sulpiride modulates striatal BOLD signal during the manipulation of information in working memory.

    PubMed

    Dodds, Chris M; Clark, Luke; Dove, Anja; Regenthal, Ralf; Baumann, Frank; Bullmore, Ed; Robbins, Trevor W; Müller, Ulrich

    2009-11-01

    Dopamine (DA) plays an important role in working memory. However, the precise functions supported by different DA receptor subtypes in different neural regions remain unclear. The present study used pharmacological, event-related fMRI to test the hypothesis that striatal dopamine is important for the manipulation of information in working memory. Twenty healthy human subjects were scanned twice, once after placebo and once after sulpiride 400 mg, a selective DA D2 receptor antagonist, while performing a verbal working memory task requiring different levels of manipulation. Whilst there was no overall effect of sulpiride on task-dependent activation, individual variation in sulpiride plasma levels predicted the effect of working memory manipulation on activation in the putamen, suggesting a dose-dependent effect of DA antagonism on a striatally based manipulation process. These effects occurred in the context of a drug-induced improvement in performance on trials requiring the manipulation of information in working memory but not on simple retrieval trials. No significant drug effects were observed in the prefrontal cortex. These results support models of dopamine function that posit a 'gating' function for dopamine D2 receptors in the striatum, which enables the flexible updating and manipulation of information in working memory.

  4. The thyrotropin receptor mutation database: update 2003.

    PubMed

    Führer, Dagmar; Lachmund, Peter; Nebel, Istvan-Tibor; Paschke, Ralf

    2003-12-01

    In 1999 we have created a TSHR mutation database compiling TSHR mutations with their basic characteristics and associated clinical conditions (www.uni-leipzig.de/innere/tshr). Since then, more than 2887 users from 36 countries have logged into the TSHR mutation database and have contributed several valuable suggestions for further improvement of the database. We now present an updated and extended version of the TSHR database to which several novel features have been introduced: 1. detailed functional characteristics on all 65 mutations (43 activating and 22 inactivating mutations) reported to date, 2. 40 pedigrees with detailed information on molecular aspects, clinical courses and treatment options in patients with gain-of-function and loss-of-function germline TSHR mutations, 3. a first compilation of site-directed mutagenesis studies, 4. references with Medline links, 5. a user friendly search tool for specific database searches, user-specific database output and 6. an administrator tool for the submission of novel TSHR mutations. The TSHR mutation database is installed as one of the locus specific HUGO mutation databases. It is listed under index TSHR 603372 (http://ariel.ucs.unimelb.edu.au/~cotton/glsdbq.htm) and can be accessed via www.uni-leipzig.de/innere/tshr.

  5. Research resource: Update and extension of a glycoprotein hormone receptors web application.

    PubMed

    Kreuchwig, Annika; Kleinau, Gunnar; Kreuchwig, Franziska; Worth, Catherine L; Krause, Gerd

    2011-04-01

    The SSFA-GPHR (Sequence-Structure-Function-Analysis of Glycoprotein Hormone Receptors) database provides a comprehensive set of mutation data for the glycoprotein hormone receptors (covering the lutropin, the FSH, and the TSH receptors). Moreover, it provides a platform for comparison and investigation of these homologous receptors and helps in understanding protein malfunctions associated with several diseases. Besides extending the data set (> 1100 mutations), the database has been completely redesigned and several novel features and analysis tools have been added to the web site. These tools allow the focused extraction of semiquantitative mutant data from the GPHR subtypes and different experimental approaches. Functional and structural data of the GPHRs are now linked interactively at the web interface, and new tools for data visualization (on three-dimensional protein structures) are provided. The interpretation of functional findings is supported by receptor morphings simulating intramolecular changes during the activation process, which thus help to trace the potential function of each amino acid and provide clues to the local structural environment, including potentially relocated spatial counterpart residues. Furthermore, double and triple mutations are newly included to allow the analysis of their functional effects related to their spatial interrelationship in structures or homology models. A new important feature is the search option and data visualization by interactive and user-defined snake-plots. These new tools allow fast and easy searches for specific functional data and thereby give deeper insights in the mechanisms of hormone binding, signal transduction, and signaling regulation. The web application "Sequence-Structure-Function-Analysis of GPHRs" is accessible on the internet at http://www.ssfa-gphr.de/.

  6. The Concise Guide to Pharmacology 2013/14: G Protein-Coupled Receptors

    PubMed Central

    Alexander, Stephen PH; Benson, Helen E; Faccenda, Elena; Pawson, Adam J; Sharman, Joanna L; Spedding, Michael; Peters, John A; Harmar, Anthony J

    2013-01-01

    The Concise Guide to PHARMACOLOGY 2013/14 provides concise overviews of the key properties of over 2000 human drug targets with their pharmacology, plus links to an open access knowledgebase of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. The full contents can be found at http://onlinelibrary.wiley.com/doi/10.1111/bph.12444/full. G protein-coupled receptors are one of the seven major pharmacological targets into which the Guide is divided, with the others being G protein-coupled receptors, ligand-gated ion channels, ion channels, catalytic receptors, nuclear hormone receptors, transporters and enzymes. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. A new landscape format has easy to use tables comparing related targets. It is a condensed version of material contemporary to late 2013, which is presented in greater detail and constantly updated on the website www.guidetopharmacology.org, superseding data presented in previous Guides to Receptors and Channels. It is produced in conjunction with NC-IUPHAR and provides the official IUPHAR classification and nomenclature for human drug targets, where appropriate. It consolidates information previously curated and displayed separately in IUPHAR-DB and the Guide to Receptors and Channels, providing a permanent, citable, point-in-time record that will survive database updates. PMID:24517644

  7. Updating stand-level forest inventories using airborne laser scanning and Landsat time series data

    NASA Astrophysics Data System (ADS)

    Bolton, Douglas K.; White, Joanne C.; Wulder, Michael A.; Coops, Nicholas C.; Hermosilla, Txomin; Yuan, Xiaoping

    2018-04-01

    Vertical forest structure can be mapped over large areas by combining samples of airborne laser scanning (ALS) data with wall-to-wall spatial data, such as Landsat imagery. Here, we use samples of ALS data and Landsat time-series metrics to produce estimates of top height, basal area, and net stem volume for two timber supply areas near Kamloops, British Columbia, Canada, using an imputation approach. Both single-year and time series metrics were calculated from annual, gap-free Landsat reflectance composites representing 1984-2014. Metrics included long-term means of vegetation indices, as well as measures of the variance and slope of the indices through time. Terrain metrics, generated from a 30 m digital elevation model, were also included as predictors. We found that imputation models improved with the inclusion of Landsat time series metrics when compared to single-year Landsat metrics (relative RMSE decreased from 22.8% to 16.5% for top height, from 32.1% to 23.3% for basal area, and from 45.6% to 34.1% for net stem volume). Landsat metrics that characterized 30-years of stand history resulted in more accurate models (for all three structural attributes) than Landsat metrics that characterized only the most recent 10 or 20 years of stand history. To test model transferability, we compared imputed attributes against ALS-based estimates in nearby forest blocks (>150,000 ha) that were not included in model training or testing. Landsat-imputed attributes correlated strongly to ALS-based estimates in these blocks (R2 = 0.62 and relative RMSE = 13.1% for top height, R2 = 0.75 and relative RMSE = 17.8% for basal area, and R2 = 0.67 and relative RMSE = 26.5% for net stem volume), indicating model transferability. These findings suggest that in areas containing spatially-limited ALS data acquisitions, imputation models, and Landsat time series and terrain metrics can be effectively used to produce wall-to-wall estimates of key inventory attributes, providing an

  8. Run-to-Run Optimization Control Within Exact Inverse Framework for Scan Tracking.

    PubMed

    Yeoh, Ivan L; Reinhall, Per G; Berg, Martin C; Chizeck, Howard J; Seibel, Eric J

    2017-09-01

    A run-to-run optimization controller uses a reduced set of measurement parameters, in comparison to more general feedback controllers, to converge to the best control point for a repetitive process. A new run-to-run optimization controller is presented for the scanning fiber device used for image acquisition and display. This controller utilizes very sparse measurements to estimate a system energy measure and updates the input parameterizations iteratively within a feedforward with exact-inversion framework. Analysis, simulation, and experimental investigations on the scanning fiber device demonstrate improved scan accuracy over previous methods and automatic controller adaptation to changing operating temperature. A specific application example and quantitative error analyses are provided of a scanning fiber endoscope that maintains high image quality continuously across a 20 °C temperature rise without interruption of the 56 Hz video.

  9. Breast cancer follow-up and management after primary treatment: American Society of Clinical Oncology clinical practice guideline update.

    PubMed

    Khatcheressian, James L; Hurley, Patricia; Bantug, Elissa; Esserman, Laura J; Grunfeld, Eva; Halberg, Francine; Hantel, Alexander; Henry, N Lynn; Muss, Hyman B; Smith, Thomas J; Vogel, Victor G; Wolff, Antonio C; Somerfield, Mark R; Davidson, Nancy E

    2013-03-01

    To provide recommendations on the follow-up and management of patients with breast cancer who have completed primary therapy with curative intent. To update the 2006 guideline of the American Society of Clinical Oncology (ASCO), a systematic review of the literature published from March 2006 through March 2012 was completed using MEDLINE and the Cochrane Collaboration Library. An Update Committee reviewed the evidence to determine whether the recommendations were in need of updating. There were 14 new publications that met inclusion criteria: nine systematic reviews (three included meta-analyses) and five randomized controlled trials. After its review and analysis of the evidence, the Update Committee concluded that no revisions to the existing ASCO recommendations were warranted. Regular history, physical examination, and mammography are recommended for breast cancer follow-up. Physical examinations should be performed every 3 to 6 months for the first 3 years, every 6 to 12 months for years 4 and 5, and annually thereafter. For women who have undergone breast-conserving surgery, a post-treatment mammogram should be obtained 1 year after the initial mammogram and at least 6 months after completion of radiation therapy. Thereafter, unless otherwise indicated, a yearly mammographic evaluation should be performed. The use of complete blood counts, chemistry panels, bone scans, chest radiographs, liver ultrasounds, pelvic ultrasounds, computed tomography scans, [(18)F]fluorodeoxyglucose-positron emission tomography scans, magnetic resonance imaging, and/or tumor markers (carcinoembryonic antigen, CA 15-3, and CA 27.29) is not recommended for routine follow-up in an otherwise asymptomatic patient with no specific findings on clinical examination.

  10. An update on the role of the 5-hydroxytryptamine6 receptor in cognitive function.

    PubMed

    Fone, Kevin C F

    2008-11-01

    As the 5-hydroxytryptamine(6) (5-HT(6)) receptor is almost exclusively expressed in the CNS, particularly in areas associated with learning and memory, many studies have examined its role in cognitive function in the rodent, as reviewed herein. Most studies, in healthy adult rats, report that 5-HT(6) receptor antagonists enhance retention of spatial learning in the Morris water maze, improve consolidation in autoshaping tasks and reverse natural forgetting in object recognition. Antagonists appear to facilitate both cholinergic and glutamatergic neurotransmission, reversing scopolamine- and NMDA receptor antagonist-induced memory impairments. Recent reports show that the 5-HT(6) receptor antagonist, PRX-07034, restores the impairment of novel object recognition produced in rats reared in social isolation, a neurodevelopmental model producing behavioural changes similar to several core symptoms seen in schizophrenia. The 5-HT(6) receptor antagonist, Ro 04-6790, modestly improved reversal learning in isolation reared but not group-housed controls in the water maze. Ro 04-6790 also improved novel object discrimination both in adult rats that received chronic intermittent phencyclidine and drug-naïve 18-month-old rats. However, more information on their effect in animal models of schizophrenia and Alzheimer's disease is required. Several selective high-affinity 5-HT(6) receptor agonists developed recently also improve object discrimination and extra-dimensional set-shifting behaviour. Thus both 5-HT(6) receptor agonist and antagonist compounds show promise as pro-cognitive agents in pre-clinical studies but the explanation for their paradoxical analogous effect is currently unclear, and is discussed in this article.

  11. NUREBASE: database of nuclear hormone receptors.

    PubMed

    Duarte, Jorge; Perrière, Guy; Laudet, Vincent; Robinson-Rechavi, Marc

    2002-01-01

    Nuclear hormone receptors are an abundant class of ligand activated transcriptional regulators, found in varying numbers in all animals. Based on our experience of managing the official nomenclature of nuclear receptors, we have developed NUREBASE, a database containing protein and DNA sequences, reviewed protein alignments and phylogenies, taxonomy and annotations for all nuclear receptors. The reviewed NUREBASE is completed by NUREBASE_DAILY, automatically updated every 24 h. Both databases are organized under a client/server architecture, with a client written in Java which runs on any platform. This client, named FamFetch, integrates a graphical interface allowing selection of families, and manipulation of phylogenies and alignments. NUREBASE sequence data is also accessible through a World Wide Web server, allowing complex queries. All information on accessing and installing NUREBASE may be found at http://www.ens-lyon.fr/LBMC/laudet/nurebase.html.

  12. Glucocorticoid receptor signaling in health and disease

    PubMed Central

    Kadmiel, Mahita; Cidlowski, John A.

    2013-01-01

    Glucocorticoids are steroid hormones regulated in a circadian and stres-associated manner to maintain various metabolic and homeostatic functions that are necessary for life. Synthetic glucocorticoids are widely prescribed drugs for many conditions including asthma, chronic obstructive pulmonary disease (COPD), and inflammatory disorders of the eye. Research in the last few years has begun to unravel the profound complexity of glucocorticoid signaling and has contributed remarkably to improved therapeutic strategies. Glucocorticoids signal through the glucocorticoid receptor, a member of the superfamily of nuclear receptors, in both genomic and non-genomic ways in almost every tissue in the human body. In this review, we will provide an update on glucocorticoid receptor signaling and highlight the role of GR signaling in physiological and pathophysiological conditions in the major organ systems in the human body. PMID:23953592

  13. Updating the landscape of direct-to-consumer pharmacogenomic testing.

    PubMed

    Filipski, Kelly K; Murphy, John D; Helzlsouer, Kathy J

    2017-01-01

    Pharmacogenomics has identified important drug-gene interactions that affect the safety and efficacy of medications. Direct-to-consumer genetic testing, when first introduced, included some pharmacogenomic-related genes. The current landscape of pharmacogenomic direct-to-consumer testing is reviewed. Prior published reviews of the literature were updated through February 2017 and a scan of the current availability of direct-to-consumer genomic testing by companies was conducted. Results of the review demonstrate a shift toward physician-approved ordering.

  14. Guideline on terminology and definitions of updating clinical guidelines: The Updating Glossary.

    PubMed

    Martínez García, Laura; Pardo-Hernández, Hector; Sanabria, Andrea Juliana; Alonso-Coello, Pablo; Penman, Katrina; McFarlane, Emma

    2018-03-01

    The Guidelines International Network (G-I-N) Updating Guidelines Working Group launched an initiative to develop a glossary (the Updating Glossary) with domains, terms, definitions, and synonyms related to updating of clinical guidelines (CGs). The steering committee developed an initial list of domains, terms, definitions, and synonyms through brainstorming and discussion. The panel members participated in three rounds of feedback to discuss, refine, and clarify the proposed terms, definitions, and synonyms. Finally, the panel members were surveyed to assess their level of agreement regarding the glossary. Eighteen terms were identified and defined: (1) continuous updating, (2) decision to update, (3) fixed updating, (4) full updating, (5) impact of the new evidence, (6) partial updating, (7) prioritization process, (8) reporting process, (9) signal for an update, (10) surveillance process, (11) time of validity, (12) timeframe, (13) tools and resources, (14) up to date, (15) update cycle, (16) update unit, (17) updated version, and (18) updating strategy. Consensus was reached for all terms, definitions, and synonyms (median agreement scores ≥ 6); except for one term. The G-I-N Updating Guidelines Working Group assembled the Updating Glossary to facilitate and improve the knowledge exchange among CGs developers, researchers, and users. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Dual energy CT with one full scan and a second sparse-view scan using structure preserving iterative reconstruction (SPIR)

    NASA Astrophysics Data System (ADS)

    Wang, Tonghe; Zhu, Lei

    2016-09-01

    Conventional dual-energy CT (DECT) reconstruction requires two full-size projection datasets with two different energy spectra. In this study, we propose an iterative algorithm to enable a new data acquisition scheme which requires one full scan and a second sparse-view scan for potential reduction in imaging dose and engineering cost of DECT. A bilateral filter is calculated as a similarity matrix from the first full-scan CT image to quantify the similarity between any two pixels, which is assumed unchanged on a second CT image since DECT scans are performed on the same object. The second CT image from reduced projections is reconstructed by an iterative algorithm which updates the image by minimizing the total variation of the difference between the image and its filtered image by the similarity matrix under data fidelity constraint. As the redundant structural information of the two CT images is contained in the similarity matrix for CT reconstruction, we refer to the algorithm as structure preserving iterative reconstruction (SPIR). The proposed method is evaluated on both digital and physical phantoms, and is compared with the filtered-backprojection (FBP) method, the conventional total-variation-regularization-based algorithm (TVR) and prior-image-constrained-compressed-sensing (PICCS). SPIR with a second 10-view scan reduces the image noise STD by a factor of one order of magnitude with same spatial resolution as full-view FBP image. SPIR substantially improves over TVR on the reconstruction accuracy of a 10-view scan by decreasing the reconstruction error from 6.18% to 1.33%, and outperforms TVR at 50 and 20-view scans on spatial resolution with a higher frequency at the modulation transfer function value of 10% by an average factor of 4. Compared with the 20-view scan PICCS result, the SPIR image has 7 times lower noise STD with similar spatial resolution. The electron density map obtained from the SPIR-based DECT images with a second 10-view scan has an

  16. Calcium-sensing receptor 20 years later

    PubMed Central

    Alfadda, Tariq I.; Saleh, Ahmad M. A.; Houillier, Pascal

    2014-01-01

    The calcium-sensing receptor (CaSR) has played an important role as a target in the treatment of a variety of disease states over the past 20 plus years. In this review, we give an overview of the receptor at the cellular level and then provide details as to how this receptor has been targeted to modulate cellular ion transport mechanisms. As a member of the G protein-coupled receptor (GPCR) family, it has a high degree of homology with a variety of other members in this class, which could explain why this receptor has been identified in so many different tissues throughout the body. This diversity of locations sets it apart from other members of the family and may explain how the receptor interacts with so many different organ systems in the body to modulate the physiology and pathophysiology. The receptor is unique in that it has two large exofacial lobes that sit in the extracellular environment and sense changes in a wide variety of environmental cues including salinity, pH, amino acid concentration, and polyamines to name just a few. It is for this reason that there has been a great deal of research associated with normal receptor physiology over the past 20 years. With the ongoing research, in more recent years a focus on the pathophysiology has emerged and the effects of receptor mutations on cellular and organ physiology have been identified. We hope that this review will enhance and update the knowledge about the importance of this receptor and stimulate future potential investigations focused around this receptor in cellular, organ, and systemic physiology and pathophysiology. PMID:24871857

  17. Comparative Functional Alanine Positional Scanning of the α-Melanocyte Stimulating Hormone and NDP-Melanocyte Stimulating Hormone Demonstrates Differential Structure-Activity Relationships at the Mouse Melanocortin Receptors.

    PubMed

    Todorovic, Aleksandar; Ericson, Mark D; Palusak, Ryan D; Sorensen, Nicholas B; Wood, Michael S; Xiang, Zhimin; Haskell-Luevano, Carrie

    2016-07-20

    The melanocortin system has been implicated in the regulation of various physiological functions including melanogenesis, steroidogenesis, energy homeostasis, and feeding behavior. Five melanocortin receptors have been identified to date and belong to the family of G protein-coupled receptors (GPCR). Post-translational modification of the proopiomelanocortin (POMC) prohormone leads to the biosynthesis of the endogenous melanocortin agonists, including α-melanocyte stimulating hormone (α-MSH), β-MSH, γ-MSH, and adrenocorticotropic hormone (ACTH). All the melanocortin agonists derived from the POMC prohormone contain a His-Phe-Arg-Trp tetrapeptide sequence that has been implicated in eliciting the pharmacological responses at the melanocortin receptors. Herein, an alanine (Ala) positional scan is reported for the endogenous α-MSH ligand and the synthetic, more potent, NDP-MSH peptide (Ac-Ser(1)-Tyr(2)-Ser(3)-Nle(4)-Glu(5)-His(6)-DPhe(7)-Arg(8)-Trp(9)-Gly(10)-Lys(11)-Pro(12)-Val(13)-NH2) at the cloned mouse melanocortin receptors to test the assumption that the structure-activity relationships of one ligand would apply to the other. Several residues outside of the postulated pharmacophore altered potency at the melanocortin receptors, most notably the 1560-, 37-, and 15-fold potency loss when the Glu(5) position of α-MSH was substituted with Ala at the mMC1R, mMC3R, and mMC4R, respectively. Importantly, the altered potencies due to Ala substitutions in α-MSH did not necessarily correlate with equivalent Ala substitutions in NDP-MSH, indicating that structural modifications and corresponding biological activities in one of these melanocortin ligands may not be predictive for the other agonist.

  18. An Environmental Scan Update, 1992-93. 2020: Perfect Vision for the Next Century.

    ERIC Educational Resources Information Center

    Friedel, J. N., Ed.

    1992-01-01

    A key component to Eastern Iowa Community College District's (EICCD) strategic planning process, called "2020 Vision: A Perfect Vision for the Future," was the publication of the report "An Environmental Scan" in 1989, which summarized major trends occurring in the external environment which may impact the community college,…

  19. Human Epidermal Growth Factor Receptor 2 Testing in Breast Cancer: American Society of Clinical Oncology/College of American Pathologists Clinical Practice Guideline Focused Update.

    PubMed

    Wolff, Antonio C; Hammond, M Elizabeth Hale; Allison, Kimberly H; Harvey, Brittany E; Mangu, Pamela B; Bartlett, John M S; Bilous, Michael; Ellis, Ian O; Fitzgibbons, Patrick; Hanna, Wedad; Jenkins, Robert B; Press, Michael F; Spears, Patricia A; Vance, Gail H; Viale, Giuseppe; McShane, Lisa M; Dowsett, Mitchell

    2018-05-30

    Purpose To update key recommendations of the American Society of Clinical Oncology/College of American Pathologists human epidermal growth factor receptor 2 (HER2) testing in breast cancer guideline. Methods Based on the signals approach, an Expert Panel reviewed published literature and research survey results on the observed frequency of less common in situ hybridization (ISH) patterns to update the recommendations. Recommendations Two recommendations addressed via correspondence in 2015 are included. First, immunohistochemistry (IHC) 2+ is defined as invasive breast cancer with weak to moderate complete membrane staining observed in > 10% of tumor cells. Second, if the initial HER2 test result in a core needle biopsy specimen of a primary breast cancer is negative, a new HER2 test may (not "must") be ordered on the excision specimen based on specific clinical criteria. The HER2 testing algorithm for breast cancer is updated to address the recommended work-up for less common clinical scenarios (approximately 5% of cases) observed when using a dual-probe ISH assay. These scenarios are described as ISH group 2 ( HER2/chromosome enumeration probe 17 [CEP17] ratio ≥ 2.0; average HER2 copy number < 4.0 signals per cell), ISH group 3 ( HER2/CEP17 ratio < 2.0; average HER2 copy number ≥ 6.0 signals per cell), and ISH group 4 ( HER2/CEP17 ratio < 2.0; average HER2 copy number ≥ 4.0 and < 6.0 signals per cell). The diagnostic approach includes more rigorous interpretation criteria for ISH and requires concomitant IHC review for dual-probe ISH groups 2 to 4 to arrive at the most accurate HER2 status designation (positive or negative) based on combined interpretation of the ISH and IHC assays. The Expert Panel recommends that laboratories using single-probe ISH assays include concomitant IHC review as part of the interpretation of all single-probe ISH assay results. Find additional information at www.asco.org/breast-cancer-guidelines .

  20. Human Epidermal Growth Factor Receptor 2 Testing in Breast Cancer: American Society of Clinical Oncology/College of American Pathologists Clinical Practice Guideline Focused Update.

    PubMed

    Wolff, Antonio C; Hammond, M Elizabeth Hale; Allison, Kimberly H; Harvey, Brittany E; Mangu, Pamela B; Bartlett, John M S; Bilous, Michael; Ellis, Ian O; Fitzgibbons, Patrick; Hanna, Wedad; Jenkins, Robert B; Press, Michael F; Spears, Patricia A; Vance, Gail H; Viale, Giuseppe; McShane, Lisa M; Dowsett, Mitchell

    2018-05-30

    - To update key recommendations of the American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) human epidermal growth factor receptor 2 (HER2) testing in breast cancer guideline. - Based on the signals approach, an Expert Panel reviewed published literature and research survey results on the observed frequency of less common in situ hybridization (ISH) patterns to update the recommendations. - Two recommendations addressed via correspondence in 2015 are included. First, immunohistochemistry (IHC) 2+ is defined as invasive breast cancer with weak to moderate complete membrane staining observed in >10% of tumor cells. Second, if the initial HER2 test result in a core needle biopsy specimen of a primary breast cancer is negative, a new HER2 test may (not "must") be ordered on the excision specimen based on specific clinical criteria. The HER2 testing algorithm for breast cancer is updated to address the recommended workup for less common clinical scenarios (approximately 5% of cases) observed when using a dual-probe ISH assay. These scenarios are described as ISH group 2 ( HER2/chromosome enumeration probe 17 [CEP17] ratio ≥2.0; average HER2 copy number <4.0 signals per cell), ISH group 3 ( HER2/CEP17 ratio <2.0; average HER2 copy number ≥6.0 signals per cell), and ISH group 4 ( HER2/CEP17 ratio <2.0; average HER2 copy number ≥4.0 and <6.0 signals per cell). The diagnostic approach includes more rigorous interpretation criteria for ISH and requires concomitant IHC review for dual-probe ISH groups 2 to 4 to arrive at the most accurate HER2 status designation (positive or negative) based on combined interpretation of the ISH and IHC assays. The Expert Panel recommends that laboratories using single-probe ISH assays include concomitant IHC review as part of the interpretation of all single-probe ISH assay results.

  1. S2RSLDB: a comprehensive manually curated, internet-accessible database of the sigma-2 receptor selective ligands.

    PubMed

    Nastasi, Giovanni; Miceli, Carla; Pittalà, Valeria; Modica, Maria N; Prezzavento, Orazio; Romeo, Giuseppe; Rescifina, Antonio; Marrazzo, Agostino; Amata, Emanuele

    2017-01-01

    Sigma (σ) receptors are accepted as a particular receptor class consisting of two subtypes: sigma-1 (σ 1 ) and sigma-2 (σ 2 ). The two receptor subtypes have specific drug actions, pharmacological profiles and molecular characteristics. The σ 2 receptor is overexpressed in several tumor cell lines, and its ligands are currently under investigation for their role in tumor diagnosis and treatment. The σ 2 receptor structure has not been disclosed, and researchers rely on σ 2 receptor radioligand binding assay to understand the receptor's pharmacological behavior and design new lead compounds. Here we present the sigma-2 Receptor Selective Ligands Database (S2RSLDB) a manually curated database of the σ 2 receptor selective ligands containing more than 650 compounds. The database is built with chemical structure information, radioligand binding affinity data, computed physicochemical properties, and experimental radioligand binding procedures. The S2RSLDB is freely available online without account login and having a powerful search engine the user may build complex queries, sort tabulated results, generate color coded 2D and 3D graphs and download the data for additional screening. The collection here reported is extremely useful for the development of new ligands endowed of σ 2 receptor affinity, selectivity, and appropriate physicochemical properties. The database will be updated yearly and in the near future, an online submission form will be available to help with keeping the database widely spread in the research community and continually updated. The database is available at http://www.researchdsf.unict.it/S2RSLDB.

  2. Dissociable Frontal–Striatal and Frontal–Parietal Networks Involved in Updating Hierarchical Contexts in Working Memory

    PubMed Central

    Nee, Derek Evan; Brown, Joshua W.

    2013-01-01

    Recent theories propose that the prefrontal cortex (PFC) is organized in a hierarchical fashion with more abstract, higher level information represented in anterior regions and more concrete, lower level information represented in posterior regions. This hierarchical organization affords flexible adjustments of action plans based on the context. Computational models suggest that such hierarchical organization in the PFC is achieved through interactions with the basal ganglia (BG) wherein the BG gate relevant contexts into the PFC. Here, we tested this proposal using functional magnetic resonance imaging (fMRI). Participants were scanned while updating working memory (WM) with 2 levels of hierarchical contexts. Consistent with PFC abstraction proposals, higher level context updates involved anterior portions of the PFC (BA 46), whereas lower level context updates involved posterior portions of the PFC (BA 6). Computational models were only partially supported as the BG were sensitive to higher, but not lower level context updates. The posterior parietal cortex (PPC) showed the opposite pattern. Analyses examining changes in functional connectivity confirmed dissociable roles of the anterior PFC–BG during higher level context updates and posterior PFC–PPC during lower level context updates. These results suggest that hierarchical contexts are organized by distinct frontal–striatal and frontal–parietal networks. PMID:22798339

  3. An Update on Non-CB1, Non-CB2 Cannabinoid Related G-Protein-Coupled Receptors

    PubMed Central

    Morales, Paula; Reggio, Patricia H.

    2017-01-01

    Abstract The endocannabinoid system (ECS) has been shown to be of great importance in the regulation of numerous physiological and pathological processes. To date, two Class A G-protein-coupled receptors (GPCRs) have been discovered and validated as the main therapeutic targets of this system: the cannabinoid receptor type 1 (CB1), which is the most abundant neuromodulatory receptor in the brain, and the cannabinoid receptor type 2 (CB2), predominantly found in the immune system among other organs and tissues. Endogenous cannabinoid receptor ligands (endocannabinoids) and the enzymes involved in their synthesis, cell uptake, and degradation have also been identified as part of the ECS. However, its complex pharmacology suggests that other GPCRs may also play physiologically relevant roles in this therapeutically promising system. In the last years, GPCRs such as GPR18 and GPR55 have emerged as possible missing members of the cannabinoid family. This categorization still stimulates strong debate due to the lack of pharmacological tools to validate it. Because of their close phylogenetic relationship, the Class A orphan GPCRs, GPR3, GPR6, and GPR12, have also been associated with the cannabinoids. Moreover, certain endo-, phyto-, and synthetic cannabinoid ligands have displayed activity at other well-established GPCRs, including the opioid, adenosine, serotonin, and dopamine receptor families. In addition, the cannabinoid receptors have also been shown to form dimers with other GPCRs triggering cross-talk signaling under specific conditions. In this mini review, we aim to provide insight into the non-CB1, non-CB2 cannabinoid-related GPCRs that have been reported thus far. We consider the physiological relevance of these molecular targets in modulating the ECS. PMID:29098189

  4. (Updated) Targeted T-Cell Therapy Shows Promise Against Triple-Negative Breast Cancer | Poster

    Cancer.gov

    (Updated May 8) A study led by the Baylor College of Medicine and supported by NCI’s Center for Cancer Research (CCR) has demonstrated that chimeric antigen receptor (CAR) T-cell therapy can be used to treat solid triple-negative breast cancer (TNBC) tumors. The investigation is the first work using CAR T-cell therapy against TEM8, a cell surface protein that is frequently

  5. Bombesin receptors and transplanted stem cells in rat brain: High-resolution scan with 99mTc BN1.1

    NASA Astrophysics Data System (ADS)

    Scopinaro, F.; Paschali, E.; Di Santo, G.; Antonellis, T.; Massari, R.; Trotta, C.; Gourni, H.; Bouziotis, P.; David, V.; Soluri, A.; Varvarigou, A. D.

    2006-12-01

    The aim of this work is to detect the presence of transplanted stem cells (TSC) in rat brain with high-resolution (HR) scintigraphy and labelled bombesin (BN). BN is a morphogen for Central Nervous System (CNS) as well as for other organs: CNS-oriented TSC over-express BN Receptors (BNR). BN is also a neurotransmitter and modulates several functions of CNS. 99mTc labelled BN-like peptide scan of CNS is the ideal method to detect growing TSC once knowing normal distribution of BNRs in CNS. HR Planar and single photon emission computerized tomography (SPECT) images of rat brain were performed with new HR detectors (Li-tech, Italy). Pertechnetate, 99mTc HMPAO and the new 99mTc BN1.1 (patented) were i.v. administered in five rats. HR SPECT of 99mTc BN1.1 detected olfactory tract, fronto-lateral cortex, cerebellum, basal ganglia and amygdale. Results of SPECT were confirmed by bio-distribution study performed after autopsy of three of the five rats. The remaining two rats underwent cerebral lesions followed by transplant of TSC. Three months later, HR scintigraphy was repeated and showed images completely different from previous basal study, with hot spot of 99mTc BN1.1 corresponding to the site of TSC transplant. Immuno-histochemistry confirmed the presence of viable TSC. Not only 99mTc BN1.1 HR scan showed viability of transplanted TSC but also the "background brain" was the still now unknown map of BNR in mammalian brain.

  6. Mini-excimer laser corneal reshaping using a scanning device

    NASA Astrophysics Data System (ADS)

    Lin, Jui T.

    1994-07-01

    In this paper we present an update on the Mini-Excimer photorefractive keratectomy (PRK) laser system with an emphasis on the scanning device. We also compare the systems of various manufacturers. This paper also presents PMMA ablation profiles and clinical results from China with over 100 cases of myopic corrections ranging from -2.5 D to -12 D. In contrast to the old technology which uses industrial-type high-power excimer lasers, the advanced Mini-Excimer system uses the most recent technology involving a compact, high repetition-rate excimer laser operated at a much smaller beam spot size of (0.8 - 1.2) mm in a scanning mode which requires a beam energy per pulse of only (0.9 - 1.2) mJ on the corneal surface to achieve the same range of fluence (or energy density) (160 - 200) mJ/cm2 as that of the high-power excimer lasers.

  7. Metabotropic glutamate receptors as therapeutic targets in Parkinson's disease: An update from the last 5 years of research.

    PubMed

    Litim, Nadhir; Morissette, Marc; Di Paolo, Thérèse

    2017-03-15

    Disturbance of glutamate neurotransmission in Parkinson's disease (PD) and l-DOPA induced dyskinesia (LID) is well documented. This review focuses on advances during the past five years on pharmacological modulation of metabotropic glutamate (mGlu) receptors in relation to anti-parkinsonian activity, LID attenuation, and neuroprotection. Drug design and characterization have led to the development of orthosteric agonists binding the same site as glutamate and Positive and Negative Allosteric modulators (PAMs and NAMs) binding sites different from the orthosteric site and offering subtype selectivity. Inhibition of group I (mGlu1 and mGlu5) receptors with NAMs and activation of group II (mGlu2 and 3 receptors) and group III (mGlu 4, 7 and 8 receptors) with PAMs and orthosteric agonists have shown their potential to inhibit glutamate release and attenuate excitotoxicity. Earlier and recent studies have led to the development of mGlu5 receptors NAMs to reduce LID and for neuroprotection, mGlu3 receptor agonists for neuroprotection while mGlu4 receptor PAMs and agonists for antiparkinsonian effects and neuroprotection. Furthermore, homo- and heterodimers of mGlu receptors are documented and highlight the complexity of the functioning of these receptors. Research on partial allosteric modulators and biased mGlu receptor allosteric modulators offer new glutamatergic drugs with better therapeutic effects and less off target adverse activity. Thus these various mGlu receptor targets will enable the development of novel drugs with improved clinical effects for normalization of glutamate transmission, treat PD and LID relief. This article is part of the Special Issue entitled 'Metabotropic Glutamate Receptors, 5 years on'. Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. Dopamine D3 receptor ligands for drug addiction treatment: update on recent findings.

    PubMed

    Le Foll, Bernard; Collo, Ginetta; Rabiner, Eugenii A; Boileau, Isabelle; Merlo Pich, Emilio; Sokoloff, Pierre

    2014-01-01

    The dopamine D3 receptor is located in the limbic area and apparently mediates selective effects on motivation to take drugs and drug-seeking behaviors, so that there has been considerable interest on the possible use of D3 receptor ligands to treat drug addiction. However, only recently selective tools allowing studying this receptor have been developed. This chapter presents an overview of findings that were presented at a symposium on the conference Dopamine 2013 in Sardinia in May 2013. Novel neurobiological findings indicate that drugs of abuse can lead to significant structural plasticity in rodent brain and that this is dependent on the availability of functional dopamine D3 autoreceptor, whose activation increased phosphorylation in the ERK pathway and in the Akt/mTORC1 pathway indicating the parallel engagement of a series of intracellular signaling pathways all involved in cell growth and survival. Preclinical findings using animal models of drug-seeking behaviors confirm that D3 antagonists have a promising profile to treat drug addiction across drugs of abuse type. Imaging the D3 is now feasible in human subjects. Notably, the development of (+)-4-propyl-9-hydroxynaphthoxazine ligand used in positron emission tomography (PET) studies in humans allows to measure D3 and D2 receptors based on the area of the brain under study. This PET ligand has been used to confirm up-regulation of D3 sites in psychostimulant users and to reveal that tobacco smoking produces elevation of dopamine at the level of D3 sites. There are now novel antagonists being developed, but also old drugs such as buspirone, that are available to test the D3 hypothesis in humans. The first results of clinical investigations are now being provided. Overall, those recent findings support further exploration of D3 ligands to treat drug addiction. © 2014 Elsevier B.V. All rights reserved.

  9. The F-SCAN system of foot pressure analysis.

    PubMed

    Young, C R

    1993-07-01

    The age of computerized gait analysis is here. There are several systems available to meet the needs of the podiatric practitioner. This author believes that the F-SCAN technology system makes a significant contribution to the practice of podiatric medicine. The system is user friendly, accurate, reproducible, and affordable. Its graphic display capabilities are colorfully attractive and easily understood. The primary focus of the F-SCAN system is that of peak pressure distribution over time. Vertical plantar pressure dispersion across the plantar surface of the foot is recorded, processed, and graphically displayed in terms of sequential gait changes. The system further allows for the manipulation of the accumulated data to present it in a more comprehensive manner. Future updates on the F-SCAN software are already close at hand and are expected to enhance the diagnostic capabilities of the system further. The four primary areas of clinical application for F-SCAN have been identified and briefly discussed. The recognition of certain biomechanical abnormalities, monitoring preorthotic and postorthotic use, evaluation of the diabetic or neuropathic foot, and presurgical and postsurgical functional examinations constitute this group. The F-SCAN system largely helps to remove some of the unavoidable guess work from essential diagnostic and therapeutic procedures. As we increase our understanding of the pathomechanics of these clinical problems, so too will we improve our management of the associated complications. Years ago, at the time when computerized gait analysis was being introduced to the podiatric profession, a frequently asked question was: What does it tell me that I don't already know or can't see by watching the patient walk?(ABSTRACT TRUNCATED AT 250 WORDS)

  10. Phytocannabinoids for Cancer Therapeutics: Recent Updates and Future Prospects.

    PubMed

    Patil, K R; Goyal, S N; Sharma, C; Patil, C R; Ojha, S

    2015-01-01

    Phytocannabinoids (pCBs) are lipid-soluble phytochemicals present in the plant, Cannabis sativa L. and non-cannabis plants which have a long history in recreation and traditional medicine. The plant and the constituents isolated were central in the discovery of the endocannabinoid system (ECS), the most new target for drug discovery. The ECS includes two G-protein-coupled receptors; the cannabinoid receptors-1 and -2 (CB1 and CB2) for marijuana's psychoactive principle Δ(9)-tetrahydrocannabinol (Δ(9)-THC), their endogenous small lipid ligands; namely anandamide (AEA) and 2-arachidonoylglycerol (2-AG), also known as endocannabinoids and the enzymes for endocannabinoid biosynthesis and degradation such as fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL). The ECS has been suggested as a pro-homeostatic and pleiotropic signaling system activated in a time- and tissue-specific way during pathological conditions including cancer. Targeting the CB1 receptors becomes a concern because of adverse psychotropic reactions. Hence, targeting the CB2 receptors or the endocannabinoid metabolizing enzymes by pCBs obtained from plants lacking psychotropic adverse reactions has garnered interest in drug discovery. These pCBs derived from plants appear safe and effective with a wider access and availability. In the recent years, several pCBs derived other than non-cannabinoid plants have been reported to bind to and functionally interact with cannabinoid receptors and appear promising candidate for drug development including cancer therapeutics. Several of them also targets the endocannabinoid metabolizing enzymes that control endocannabinoid levels. In this article, we summarize and critically discuss the updates and future prospects of the pCBs as novel and promising candidates for cancer therapeutics.

  11. Incidentally Detected Thyroid Follicular Neoplasm on Somatostatin Receptor Imaging and Post-therapy Scan.

    PubMed

    Sood, Apurva; Singh, Harpreet; Sood, Ashwani; Basher, Rajender Kumar; Mittal, Bhagwant Rai

    2017-01-01

    Peptide receptor radionuclide therapy (PRRT) either using Lu-177 or Y-90 peptide radiopharmaceuticals has emerged as promising treatment modality in patients with inoperable metastatic neuroendocrine tumour (NET) including medullary thyroid cancer, because of overexpression of somatostatin receptor 2 (sstr-2) on these cells. The several investigators have used PRRT in non-iodine avid differentiated thyroid cancer patients with limited success, where other treatment modalities have failed, probably due to faint sstr-2 expression in these lesions. However Hurthle cell neoplasms being predominantly non-iodine avid lesions have shown sstr-2 over-expression. The present case of inoperable NET patient imaged and treated with radiolabelled somatostatin analogue showed incidentally detected thyroid lesion highlighting the its importance in imaging and treatment in these type of thyroid malignancies.

  12. Technical Note: Spot characteristic stability for proton pencil beam scanning.

    PubMed

    Chen, Chin-Cheng; Chang, Chang; Moyers, Michael F; Gao, Mingcheng; Mah, Dennis

    2016-02-01

    The spot characteristics for proton pencil beam scanning (PBS) were measured and analyzed over a 16 month period, which included one major site configuration update and six cyclotron interventions. The results provide a reference to establish the quality assurance (QA) frequency and tolerance for proton pencil beam scanning. A simple treatment plan was generated to produce an asymmetric 9-spot pattern distributed throughout a field of 16 × 18 cm for each of 18 proton energies (100.0-226.0 MeV). The delivered fluence distribution in air was measured using a phosphor screen based CCD camera at three planes perpendicular to the beam line axis (x-ray imaging isocenter and up/down stream 15.0 cm). The measured fluence distributions for each energy were analyzed using in-house programs which calculated the spot sizes and positional deviations of the Gaussian shaped spots. Compared to the spot characteristic data installed into the treatment planning system, the 16-month averaged deviations of the measured spot sizes at the isocenter plane were 2.30% and 1.38% in the IEC gantry x and y directions, respectively. The maximum deviation was 12.87% while the minimum deviation was 0.003%, both at the upstream plane. After the collinearity of the proton and x-ray imaging system isocenters was optimized, the positional deviations of the spots were all within 1.5 mm for all three planes. During the site configuration update, spot positions were found to deviate by 6 mm until the tuning parameters file was properly restored. For this beam delivery system, it is recommended to perform a spot size and position check at least monthly and any time after a database update or cyclotron intervention occurs. A spot size deviation tolerance of <15% can be easily met with this delivery system. Deviations of spot positions were <2 mm at any plane up/down stream 15 cm from the isocenter.

  13. Incidentally Detected Thyroid Follicular Neoplasm on Somatostatin Receptor Imaging and Post-therapy Scan

    PubMed Central

    Sood, Apurva; Singh, Harpreet; Sood, Ashwani; Basher, Rajender Kumar; Mittal, Bhagwant Rai

    2017-01-01

    Peptide receptor radionuclide therapy (PRRT) either using Lu-177 or Y-90 peptide radiopharmaceuticals has emerged as promising treatment modality in patients with inoperable metastatic neuroendocrine tumour (NET) including medullary thyroid cancer, because of overexpression of somatostatin receptor 2 (sstr-2) on these cells. The several investigators have used PRRT in non-iodine avid differentiated thyroid cancer patients with limited success, where other treatment modalities have failed, probably due to faint sstr-2 expression in these lesions. However Hurthle cell neoplasms being predominantly non-iodine avid lesions have shown sstr-2 over-expression. The present case of inoperable NET patient imaged and treated with radiolabelled somatostatin analogue showed incidentally detected thyroid lesion highlighting the its importance in imaging and treatment in these type of thyroid malignancies. PMID:28680210

  14. Targeting striatal metabotropic glutamate receptor type 5 in Parkinson's disease: bridging molecular studies and clinical trials.

    PubMed

    Vallano, A; Fernandez-Duenas, V; Garcia-Negredo, G; Quijada, M A; Simon, C P; Cuffí, M L; Carbonell, L; Sanchez, S; Arnau, J M; Ciruela, F

    2013-12-01

    Metabotropic glutamate (mGlu) receptors are G protein-coupled receptors expressed primarily on neurons and glial cells modulating the effects of glutamatergic neurotransmission. The pharmacological manipulation of these receptors has been postulated to be valuable in the management of some neurological disorders. Accordingly, the targeting of mGlu5 receptors as a therapeutic approach for Parkinson's disease (PD) has been proposed, especially to manage the adverse symptoms associated to chronic treatment with classical PD drugs. Thus, the specific pharmacological blocking of mGlu5 receptors constitutes one of the most attractive non-dopaminergic-based strategies for PD management in general and for the L-DOPA-induced dyskinesia (LID) in particular. Overall, we provide here an update of the current state of the art of these mGlu5 receptor-based approaches that are under clinical study as agents devoted to alleviate PD symptoms.

  15. (Updated) Targeted T-Cell Therapy Shows Promise Against Triple-Negative Breast Cancer | Poster

    Cancer.gov

    (Updated May 8) A study led by the Baylor College of Medicine and supported by NCI’s Center for Cancer Research (CCR) has demonstrated that chimeric antigen receptor (CAR) T-cell therapy can be used to treat solid triple-negative breast cancer (TNBC) tumors. The investigation is the first work using CAR T-cell therapy against TEM8, a cell surface protein that is frequently overexpressed both in TNBC cells and cells lining the blood vessels that sustain TNBC tumors.

  16. a Bottom-Up Geosptial Data Update Mechanism for Spatial Data Infrastructure Updating

    NASA Astrophysics Data System (ADS)

    Tian, W.; Zhu, X.; Liu, Y.

    2012-08-01

    Currently, the top-down spatial data update mechanism has made a big progress and it is wildly applied in many SDI (spatial data infrastructure). However, this mechanism still has some issues. For example, the update schedule is limited by the professional department's project, usually which is too long for the end-user; the data form collection to public cost too much time and energy for professional department; the details of geospatial information does not provide sufficient attribute, etc. Thus, how to deal with the problems has become the effective shortcut. Emerging Internet technology, 3S technique and geographic information knowledge which is popular in the public promote the booming development of geoscience in volunteered geospatial information. Volunteered geospatial information is the current "hotspot", which attracts many researchers to study its data quality and credibility, accuracy, sustainability, social benefit, application and so on. In addition to this, a few scholars also pay attention to the value of VGI to support the SDI updating. And on that basis, this paper presents a bottom-up update mechanism form VGI to SDI, which includes the processes of match homonymous elements between VGI and SDI vector data , change data detection, SDI spatial database update and new data product publication to end-users. Then, the proposed updating cycle is deeply discussed about the feasibility of which can detect the changed elements in time and shorten the update period, provide more accurate geometry and attribute data for spatial data infrastructure and support update propagation.

  17. Working Memory Updating Latency Reflects the Cost of Switching between Maintenance and Updating Modes of Operation

    ERIC Educational Resources Information Center

    Kessler, Yoav; Oberauer, Klaus

    2014-01-01

    Updating and maintenance of information are 2 conflicting demands on working memory (WM). We examined the time required to update WM (updating latency) as a function of the sequence of updated and not-updated items within a list. Participants held a list of items in WM and updated a variable subset of them in each trial. Four experiments that vary…

  18. Vitamin D receptor variants in 192 patients with schizophrenia and other psychiatric diseases.

    PubMed

    Yan, Jin; Feng, Jinong; Craddock, Nick; Jones, Ian R; Cook, Edwin H; Goldman, David; Heston, Leonard L; Chen, Jiesheng; Burkhart, Patricia; Li, Wenyan; Shibayama, Akane; Sommer, Steve S

    Intriguing parallels have been noted previously between the biology of Vitamin D and the epidemiology of schizophrenia. We have scanned the Vitamin D receptor (VDR) gene by DOVAM-S (Detection of Virtually All Mutations-SSCP), a robotically enhanced multiplexed scanning method. In total, 100 patients with schizophrenia (86 Caucasians and 14 African-Americans) were scanned. In addition, pilot experiments were performed in patients with bipolar disorder (BPD) (24), autism (24), attention deficit hyperactivity disorder (ADHD) (24), and alcoholism (20). A total of 762 kb of the VDR genomic sequence was scanned. R208N and V339I were each found in one African-American patient, while absent in 35 African-American controls without schizophrenia (2/14 versus 0/35, P=0.08). Within the power of the study (> or =1.6-fold relative risk), the common M1T variant is not associated with schizophrenia. In the 92 scanned patients with other psychiatric diseases, R173S was found in a single patient with bipolar disorder. In conclusion, we describe three novel structural variants of the Vitamin D receptor. Further study is required to clarify their role, if any, in psychiatric disease.

  19. Invertebrate Gonadotropin-Releasing Hormone-Related Peptides and Their Receptors: An Update

    PubMed Central

    Sakai, Tsubasa; Shiraishi, Akira; Kawada, Tsuyoshi; Matsubara, Shin; Aoyama, Masato; Satake, Honoo

    2017-01-01

    Gonadotropin-releasing hormones (GnRHs) play pivotal roles in reproductive functions via the hypothalamus, pituitary, and gonad axis, namely, HPG axis in vertebrates. GnRHs and their receptors (GnRHRs) are likely to be conserved in invertebrate deuterostomes and lophotrochozoans. All vertebrate and urochordate GnRHs are composed of 10 amino acids, whereas protostome, echinoderm, and amphioxus GnRH-like peptides are 11- or 12-residue peptide containing two amino acids after an N-terminal pyro-Glu. In urochordates, Halocynthia roretzi GnRH gene encodes two GnRH peptide sequences, whereas two GnRH genes encode three different GnRH peptides in Ciona intestinalis. These findings indicate the species-specific diversification of GnRHs. Intriguingly, the major signaling pathway for GnRHRs is intracellular Ca2+ mobilization in chordates, echinoderms, and protostomes, whereas Ciona GnRHRs (Ci-GnRHRs) are endowed with multiple GnRHergic cAMP production pathways in a ligand-selective manner. Moreover, the ligand-specific modulation of signal transduction via heterodimerization among Ci-GnRHR paralogs suggests the species-specific development of fine-tuning of gonadal functions in ascidians. Echinoderm GnRH-like peptides show high sequence differences compared to those of protostome counterparts, leading to the difficulty in classification of peptides and receptors. These findings also show both the diversity and conservation of GnRH signaling systems in invertebrates. The lack of the HPG axis in invertebrates indicates that biological functions of GnRHs are not release of gonadotropins in current invertebrates and common ancestors of vertebrates and invertebrates. To date, authentic or putative GnRHRs have been characterized from various echinoderms and protostomes as well as chordates and the mRNAs have been found to be distributed not only reproductive organs but also other tissues. Collectively, these findings further support the notion that invertebrate GnRHs have

  20. Dynamic scan control in STEM: Spiral scans

    DOE PAGES

    Lupini, Andrew R.; Borisevich, Albina Y.; Kalinin, Sergei V.; ...

    2016-06-13

    Here, scanning transmission electron microscopy (STEM) has emerged as one of the foremost techniques to analyze materials at atomic resolution. However, two practical difficulties inherent to STEM imaging are: radiation damage imparted by the electron beam, which can potentially damage or otherwise modify the specimen and slow-scan image acquisition, which limits the ability to capture dynamic changes at high temporal resolution. Furthermore, due in part to scan flyback corrections, typical raster scan methods result in an uneven distribution of dose across the scanned area. A method to allow extremely fast scanning with a uniform residence time would enable imaging atmore » low electron doses, ameliorating radiation damage and at the same time permitting image acquisition at higher frame-rates while maintaining atomic resolution. The practical complication is that rastering the STEM probe at higher speeds causes significant image distortions. Non-square scan patterns provide a solution to this dilemma and can be tailored for low dose imaging conditions. Here, we develop a method for imaging with alternative scan patterns and investigate their performance at very high scan speeds. A general analysis for spiral scanning is presented here for the following spiral scan functions: Archimedean, Fermat, and constant linear velocity spirals, which were tested for STEM imaging. The quality of spiral scan STEM images is generally comparable with STEM images from conventional raster scans, and the dose uniformity can be improved.« less

  1. Dynamic scan control in STEM: Spiral scans

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Lupini, Andrew R.; Borisevich, Albina Y.; Kalinin, Sergei V.

    Here, scanning transmission electron microscopy (STEM) has emerged as one of the foremost techniques to analyze materials at atomic resolution. However, two practical difficulties inherent to STEM imaging are: radiation damage imparted by the electron beam, which can potentially damage or otherwise modify the specimen and slow-scan image acquisition, which limits the ability to capture dynamic changes at high temporal resolution. Furthermore, due in part to scan flyback corrections, typical raster scan methods result in an uneven distribution of dose across the scanned area. A method to allow extremely fast scanning with a uniform residence time would enable imaging atmore » low electron doses, ameliorating radiation damage and at the same time permitting image acquisition at higher frame-rates while maintaining atomic resolution. The practical complication is that rastering the STEM probe at higher speeds causes significant image distortions. Non-square scan patterns provide a solution to this dilemma and can be tailored for low dose imaging conditions. Here, we develop a method for imaging with alternative scan patterns and investigate their performance at very high scan speeds. A general analysis for spiral scanning is presented here for the following spiral scan functions: Archimedean, Fermat, and constant linear velocity spirals, which were tested for STEM imaging. The quality of spiral scan STEM images is generally comparable with STEM images from conventional raster scans, and the dose uniformity can be improved.« less

  2. Investing in updating: how do conclusions change when Cochrane systematic reviews are updated?

    PubMed Central

    French, Simon D; McDonald, Steve; McKenzie, Joanne E; Green, Sally E

    2005-01-01

    Background Cochrane systematic reviews aim to provide readers with the most up-to-date evidence on the effects of healthcare interventions. The policy of updating Cochrane reviews every two years consumes valuable time and resources and may not be appropriate for all reviews. The objective of this study was to examine the effect of updating Cochrane systematic reviews over a four year period. Methods This descriptive study examined all completed systematic reviews in the Cochrane Database of Systematic Reviews (CDSR) Issue 2, 1998. The latest version of each of these reviews was then identified in CDSR Issue 2, 2002 and changes in the review were described. For reviews that were updated within this time period and had additional studies, we determined whether their conclusion had changed and if there were factors that were predictive of this change. Results A total of 377 complete reviews were published in CDSR Issue 2, 1998. In Issue 2, 2002, 14 of these reviews were withdrawn and one was split, leaving 362 reviews to examine for the purpose of this study. Of these reviews, 254 (70%) were updated. Of these updated reviews, 23 (9%) had a change in conclusion. Both an increase in precision and a change in statistical significance of the primary outcome were predictive of a change in conclusion of the review. Conclusion The concerns around a lack of updating for some reviews may not be justified considering the small proportion of updated reviews that resulted in a changed conclusion. A priority-setting approach to the updating of Cochrane systematic reviews may be more appropriate than a time-based approach. Updating all reviews as frequently as every two years may not be necessary, however some reviews may need to be updated more often than every two years. PMID:16225692

  3. Correlating Fluorescence and High-Resolution Scanning Electron Microscopy (HRSEM) for the study of GABAA receptor clustering induced by inhibitory synaptic plasticity.

    PubMed

    Orlando, Marta; Ravasenga, Tiziana; Petrini, Enrica Maria; Falqui, Andrea; Marotta, Roberto; Barberis, Andrea

    2017-10-23

    Both excitatory and inhibitory synaptic contacts display activity dependent dynamic changes in their efficacy that are globally termed synaptic plasticity. Although the molecular mechanisms underlying glutamatergic synaptic plasticity have been extensively investigated and described, those responsible for inhibitory synaptic plasticity are only beginning to be unveiled. In this framework, the ultrastructural changes of the inhibitory synapses during plasticity have been poorly investigated. Here we combined confocal fluorescence microscopy (CFM) with high resolution scanning electron microscopy (HRSEM) to characterize the fine structural rearrangements of post-synaptic GABA A Receptors (GABA A Rs) at the nanometric scale during the induction of inhibitory long-term potentiation (iLTP). Additional electron tomography (ET) experiments on immunolabelled hippocampal neurons allowed the visualization of synaptic contacts and confirmed the reorganization of post-synaptic GABA A R clusters in response to chemical iLTP inducing protocol. Altogether, these approaches revealed that, following the induction of inhibitory synaptic potentiation, GABA A R clusters increase in size and number at the post-synaptic membrane with no other major structural changes of the pre- and post-synaptic elements.

  4. Detection of muscarinic receptors in the human lung using PET.

    PubMed

    Visser, T J; van Waarde, A; van der Mark, T W; Kraan, J; Ensing, K; Willemsen, A T; Elsinga, P H; Vaalburg, W

    1999-08-01

    The characterization of pulmonary muscarinic receptors with PET is still in its infancy. Because approximately 70% of the lungs consists of air and pulmonary muscarinic receptor densities are low, ligands with high receptor affinity are required to obtain reasonable signal-to-noise ratios on PET images. Therefore, the potent 11C-labeled muscarinic antagonist N-methyl-piperidin-4-yl 2-cyclohexyl-2-hydroxy-2-phenylacetate methiodide ([R]-VC-002) was developed. We administered this radioligand to four healthy human volunteers to examine its suitability for studying pulmonary muscarinic receptors in vivo. [11C]VC-002 (185 MBq, specific activity > 7.4 TBq/mmol) was intravenously injected on 2 separate days, with an interval of at least 1 wk. On the first day the volunteers were not pretreated, but on the second day they received the anticholinergic glycopyrronium bromide (Robinul; 2 x 0.1 mg intravenous) 25 and 30 min before the injection of the radiopharmaceutical. C[15O]O scans (approximately 740 MBq [20 mCi] by inhalation) were acquired before the receptor scan to calculate pulmonary blood volume. On PET images of the thorax, the lungs were clearly visible. After the volunteer was pretreated with glycopyrronium bromide, pulmonary uptake of the radioligand was reduced to 32%+/-12% of the control value at 60 min postinjection and the lungs could no longer be seen. (R)-[11C]-VC-002 was rapidly cleared from plasma and was slowly metabolized during the time course (60 min) of the PET scan. The fraction of radioligand representing parent compound decreased from 99.9% at the time of injection to 82% at 40-60 min postinjection, both in the presence and absence of Robinul. Pulmonary tissue-to-plasma ratios, calculated on a count-per-minute-per-gram basis, reached a plateau value of 17.8+/-1.2 at 40-50 min postinjection. [11C]VC-002 appears to be suitable for in vivo studies of pulmonary cholinoceptors.

  5. Memory Updating and Mental Arithmetic

    PubMed Central

    Han, Cheng-Ching; Yang, Tsung-Han; Lin, Chia-Yuan; Yen, Nai-Shing

    2016-01-01

    Is domain-general memory updating ability predictive of calculation skills or are such skills better predicted by the capacity for updating specifically numerical information? Here, we used multidigit mental multiplication (MMM) as a measure for calculating skill as this operation requires the accurate maintenance and updating of information in addition to skills needed for arithmetic more generally. In Experiment 1, we found that only individual differences with regard to a task updating numerical information following addition (MUcalc) could predict the performance of MMM, perhaps owing to common elements between the task and MMM. In Experiment 2, new updating tasks were designed to clarify this: a spatial updating task with no numbers, a numerical task with no calculation, and a word task. The results showed that both MUcalc and the spatial task were able to predict the performance of MMM but only with the more difficult problems, while other updating tasks did not predict performance. It is concluded that relevant processes involved in updating the contents of working memory support mental arithmetic in adults. PMID:26869971

  6. ISO Standards Update

    EPA Science Inventory

    This presentation provides a brief update on activities of ISO (International Organization for Standardization) TC (Technical Committee) 285, Clean Cooking Solutions. Slides include information on: (1) Working Group project status updates, (2) background on laboratory and field ...

  7. SCAN+

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Kenneth Krebs, John Svoboda

    2009-11-01

    SCAN+ is a software application specifically designed to control the positioning of a gamma spectrometer by a two dimensional translation system above spent fuel bundles located in a sealed spent fuel cask. The gamma spectrometer collects gamma spectrum information for the purpose of spent fuel cask fuel loading verification. SCAN+ performs manual and automatic gamma spectrometer positioning functions as-well-as exercising control of the gamma spectrometer data acquisitioning functions. Cask configuration files are used to determine the positions of spent fuel bundles. Cask scanning files are used to determine the desired scan paths for scanning a spent fuel cask allowing formore » automatic unattended cask scanning that may take several hours.« less

  8. Research Resource: A Reference Transcriptome for Constitutive Androstane Receptor and Pregnane X Receptor Xenobiotic Signaling

    PubMed Central

    Ochsner, Scott A.; Tsimelzon, Anna; Dong, Jianrong; Coarfa, Cristian

    2016-01-01

    The pregnane X receptor (PXR) (PXR/NR1I3) and constitutive androstane receptor (CAR) (CAR/NR1I2) members of the nuclear receptor (NR) superfamily of ligand-regulated transcription factors are well-characterized mediators of xenobiotic and endocrine-disrupting chemical signaling. The Nuclear Receptor Signaling Atlas maintains a growing library of transcriptomic datasets involving perturbations of NR signaling pathways, many of which involve perturbations relevant to PXR and CAR xenobiotic signaling. Here, we generated a reference transcriptome based on the frequency of differential expression of genes across 159 experiments compiled from 22 datasets involving perturbations of CAR and PXR signaling pathways. In addition to the anticipated overrepresentation in the reference transcriptome of genes encoding components of the xenobiotic stress response, the ranking of genes involved in carbohydrate metabolism and gonadotropin action sheds mechanistic light on the suspected role of xenobiotics in metabolic syndrome and reproductive disorders. Gene Set Enrichment Analysis showed that although acetaminophen, chlorpromazine, and phenobarbital impacted many similar gene sets, differences in direction of regulation were evident in a variety of processes. Strikingly, gene sets representing genes linked to Parkinson's, Huntington's, and Alzheimer's diseases were enriched in all 3 transcriptomes. The reference xenobiotic transcriptome will be supplemented with additional future datasets to provide the community with a continually updated reference transcriptomic dataset for CAR- and PXR-mediated xenobiotic signaling. Our study demonstrates how aggregating and annotating transcriptomic datasets, and making them available for routine data mining, facilitates research into the mechanisms by which xenobiotics and endocrine-disrupting chemicals subvert conventional NR signaling modalities. PMID:27409825

  9. Research Resource: A Reference Transcriptome for Constitutive Androstane Receptor and Pregnane X Receptor Xenobiotic Signaling.

    PubMed

    Ochsner, Scott A; Tsimelzon, Anna; Dong, Jianrong; Coarfa, Cristian; McKenna, Neil J

    2016-08-01

    The pregnane X receptor (PXR) (PXR/NR1I3) and constitutive androstane receptor (CAR) (CAR/NR1I2) members of the nuclear receptor (NR) superfamily of ligand-regulated transcription factors are well-characterized mediators of xenobiotic and endocrine-disrupting chemical signaling. The Nuclear Receptor Signaling Atlas maintains a growing library of transcriptomic datasets involving perturbations of NR signaling pathways, many of which involve perturbations relevant to PXR and CAR xenobiotic signaling. Here, we generated a reference transcriptome based on the frequency of differential expression of genes across 159 experiments compiled from 22 datasets involving perturbations of CAR and PXR signaling pathways. In addition to the anticipated overrepresentation in the reference transcriptome of genes encoding components of the xenobiotic stress response, the ranking of genes involved in carbohydrate metabolism and gonadotropin action sheds mechanistic light on the suspected role of xenobiotics in metabolic syndrome and reproductive disorders. Gene Set Enrichment Analysis showed that although acetaminophen, chlorpromazine, and phenobarbital impacted many similar gene sets, differences in direction of regulation were evident in a variety of processes. Strikingly, gene sets representing genes linked to Parkinson's, Huntington's, and Alzheimer's diseases were enriched in all 3 transcriptomes. The reference xenobiotic transcriptome will be supplemented with additional future datasets to provide the community with a continually updated reference transcriptomic dataset for CAR- and PXR-mediated xenobiotic signaling. Our study demonstrates how aggregating and annotating transcriptomic datasets, and making them available for routine data mining, facilitates research into the mechanisms by which xenobiotics and endocrine-disrupting chemicals subvert conventional NR signaling modalities.

  10. Immunologic analysis of human breast cancer progesterone receptors. 1. Immunonaffinity purification of transformed receptors and production of monoclonal antibodies

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Estes, P.A.; Suba, E.J.; Lawler-Heavner, J.

    1987-09-22

    A monoclonal antibody (MAb), designated PR-6, produced against chick oviduct progesterone receptors cross-reacts with the M/sub r/ 120,000 human B receptors. An immunomatrix prepared with PR-6 was used to purify progesterone receptors (PR) from T47D human breast cancer cells. Single-step immunoaffinity chromatography results in enrichment of B receptors (identified by immunoblot with PR-6 and by photoaffinity labeling with (/sup 3/H)promegestone) to a specific activity of 1915 pmol/mg of protein (or 23% purity) and with 27% yield. Purity and yields as judged by gel electrophoresis and densitometric scanning of the B protein were approximately 1.7-fold higher due to partial loss inmore » hormone binding activity at the elution step. B receptors purified under these conditions are transformed and biologically active. They were maintained as undergraded 120-kDa doublets and retained both hormone and DNA binding activities. These purified B receptors were used as immunogen for production of four monoclonal antibodies against human PR. Three of the MAbs, designated as B-30 (IgG/sub 1/), B-64 (IgG/sub 1/), and B-11 (IgM), are specific for B receptors. The fourth MAb, A/B-52 (IgG/sub 1/), reacts with both A and B receptors. The IgG MAbs are monospecific for human PR since they recognize and absorb native receptor-hormone complexes, displace the sedimentation of 4S receptors on salt containing sucrose gradients, and, by immunoblot assay of crude T47D cytosol, react only with receptor polypeptides. Although mice were injected with B receptors only, production of A/B-52 which recognized both A and B receptors provides evidence that these two proteins share regions of structural homology.« less

  11. The new scanning iron lidar, current state and future developments

    NASA Astrophysics Data System (ADS)

    Lautenbach, J.; Höffner, J.; Menzel, P.; Keller, P.

    2005-08-01

    This paper gives an update on the design and developments of the new scanning Doppler iron temperature lidar. Continuous temperature profiles in the altitude range from 50 to 105 km are derived by using the iron resonance and Rayleigh backscatter signal of this lidar. We show a common volume measurement with the well established potassium and Rayleigh-Mie-Raman (RMR) lidar at the Leibniz-Institute of Atmospheric Physics (IAP) in Kühlungsborn (Germany, 54°N). The iron lidar temperatures match quite well and have an uncertainty of 0.4K at the top of the iron layer. Improvements for daylight capability are under development and will be pointed out.

  12. 123I-labelled vasoactive intestinal peptide receptor scintigraphy in patients with colorectal cancer.

    PubMed Central

    Raderer, M.; Kurtaran, A.; Hejna, M.; Vorbeck, F.; Angelberger, P.; Scheithauer, W.; Virgolini, I.

    1998-01-01

    Recent studies have shown that various gastrointestinal tumours express substantial amounts of vasoactive intestinal peptide (VIP) receptors. Based on these observations, we have developed a receptor scintigraphy using [123I]VIP as a radioligand. An initial series performed at our institution showed promising potential for visualization of various gastrointestinal adenocarcinomas by means of [123I]VIP. In this article, we now report the results obtained in 80 consecutive patients with colorectal adenocarcinoma. Eighty consecutive patients with histologically verified colorectal cancer underwent scanning by means of [123I]VIP (1 microg, approximately 150 MBq). Thirteen patients were free of tumour after complete resection of Dukes' C cancer, eight patients presented with primary and 14 with locally recurrent tumours but were free of metastases. Ten patients had locally recurrent disease and liver, lung or lymph node metastases. Disease confined to organ metastases (i.e. liver, lung or lymph nodes) was present in 35 patients. The size of the primary or recurrent tumours ranged between 3 and 6 cm, and the size of metastases was between 1 and 13 cm in diameter. Scan results were evaluated independently by two nuclear medicine physicians in a blinded way, and results were then compared with computerized tomography (CT)scans not older than 4 weeks. Seven out of eight primary (87%) and 21 out of 24 (82%) locally relapsing cancers were imaged with [123I]VIP. Negative VIP scans were obtained in all 13 patients in whom the cancers had been curatively resected. All patients with lymph node metastases showed positive VIP scans (four out of four), and positive scans were obtained in 25 out of 28 (89%) patients with liver metastases and in two out of three cases with lung metastases. In four patients with relapsing cancer, the VIP scan indicated the presence of disease before CT, and in two patients the diagnosis of scar tissue instead of a local recurrence of rectal cancer as

  13. Colchicine--Update on mechanisms of action and therapeutic uses.

    PubMed

    Leung, Ying Ying; Yao Hui, Laura Li; Kraus, Virginia B

    2015-12-01

    To review the literature and provide an update on the mechanisms of action and therapeutic uses of oral colchicine in arthritis and inflammatory conditions. We performed PubMed database searches through June 2014 for relevant studies in the English literature published since the last update of colchicine in 2008. Searches encompassed colchicine mechanisms of action and clinical applications in medical conditions. A total of 381 articles were reviewed. The primary mechanism of action of colchicine is tubulin disruption. This leads to subsequent down regulation of multiple inflammatory pathways and modulation of innate immunity. Newly described mechanisms include various inhibitory effects on macrophages including the inhibition of the NACHT-LRRPYD-containing protein 3 (NALP3) inflammasome, inhibition of pore formation activated by purinergic receptors P2X7 and P2X2, and stimulation of dendritic cell maturation and antigen presentation. Colchicine also has anti-fibrotic activities and various effects on endothelial function. The therapeutic use of colchicine has extended beyond gouty arthritis and familial Mediterranean fever, to osteoarthritis, pericarditis, and atherosclerosis. Further understanding of the mechanisms of action underlying the therapeutic efficacy of colchicine will lead to its potential use in a variety of conditions. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. Source Update Capture in Information Agents

    NASA Technical Reports Server (NTRS)

    Ashish, Naveen; Kulkarni, Deepak; Wang, Yao

    2003-01-01

    In this paper we present strategies for successfully capturing updates at Web sources. Web-based information agents provide integrated access to autonomous Web sources that can get updated. For many information agent applications we are interested in knowing when a Web source to which the application provides access, has been updated. We may also be interested in capturing all the updates at a Web source over a period of time i.e., detecting the updates and, for each update retrieving and storing the new version of data. Previous work on update and change detection by polling does not adequately address this problem. We present strategies for intelligently polling a Web source for efficiently capturing changes at the source.

  15. An Update on Tardive Dyskinesia: From Phenomenology to Treatment

    PubMed Central

    Waln, Olga; Jankovic, Joseph

    2013-01-01

    Tardive dyskinesia (TD), characterized by oro-buccal-lingual stereotypy, can manifest in the form of akathisia, dystonia, tics, tremor, chorea, or as a combination of different types of abnormal movements. In addition to movement disorders (including involuntary vocalizations), patients with TD may have a variety of sensory symptoms, such as urge to move (as in akathisia), paresthesias, and pain. TD is a form of tardive syndrome—a group of iatrogenic hyperkinetic and hypokinetic movement disorders caused by dopamine receptor-blocking agents. The pathophysiology of TD remains poorly understood, and treatment of this condition is often challenging. In this update, we provide the most current information on the history, nomenclature, etiology, pathophysiology, epidemiology, phenomenology, differential diagnosis, and treatment of TD. PMID:23858394

  16. 2000 Montana state rail plan update

    DOT National Transportation Integrated Search

    2000-01-01

    This 2000 Montana Rail Plan Update is a comprehensive update of the State Rail Plan. The purpose of this update is to review the State's role in rail planning, retain eligibility for Local Rail Freight Assistance (LRFA) funding, update the descriptio...

  17. Data update in a land information network

    NASA Astrophysics Data System (ADS)

    Mullin, Robin C.

    1988-01-01

    The on-going update of data exchanged in a land information network is examined. In the past, major developments have been undertaken to enable the exchange of data between land information systems. A model of a land information network and the data update process have been developed. Based on these, a functional description of the database and software to perform data updating is presented. A prototype of the data update process was implemented using the ARC/INFO geographic information system. This was used to test four approaches to data updating, i.e., bulk, block, incremental, and alert updates. A bulk update is performed by replacing a complete file with an updated file. A block update requires that the data set be partitioned into blocks. When an update occurs, only the blocks which are affected need to be transferred. An incremental update approach records each feature which is added or deleted and transmits only the features needed to update the copy of the file. An alert is a marker indicating that an update has occurred. It can be placed in a file to warn a user that if he is active in an area containing markers, updated data is available. The four approaches have been tested using a cadastral data set.

  18. Reporting Items for Updated Clinical Guidelines: Checklist for the Reporting of Updated Guidelines (CheckUp)

    PubMed Central

    Vernooij, Robin W. M.; Alonso-Coello, Pablo; Brouwers, Melissa

    2017-01-01

    Background Scientific knowledge is in constant development. Consequently, regular review to assure the trustworthiness of clinical guidelines is required. However, there is still a lack of preferred reporting items of the updating process in updated clinical guidelines. The present article describes the development process of the Checklist for the Reporting of Updated Guidelines (CheckUp). Methods and Findings We developed an initial list of items based on an overview of research evidence on clinical guideline updating, the Appraisal of Guidelines for Research and Evaluation (AGREE) II Instrument, and the advice of the CheckUp panel (n = 33 professionals). A multistep process was used to refine this list, including an assessment of ten existing updated clinical guidelines, interviews with key informants (response rate: 54.2%; 13/24), a three-round Delphi consensus survey with the CheckUp panel (33 participants), and an external review with clinical guideline methodologists (response rate: 90%; 53/59) and users (response rate: 55.6%; 10/18). CheckUp includes 16 items that address (1) the presentation of an updated guideline, (2) editorial independence, and (3) the methodology of the updating process. In this article, we present the methodology to develop CheckUp and include as a supplementary file an explanation and elaboration document. Conclusions CheckUp can be used to evaluate the completeness of reporting in updated guidelines and as a tool to inform guideline developers about reporting requirements. Editors may request its completion from guideline authors when submitting updated guidelines for publication. Adherence to CheckUp will likely enhance the comprehensiveness and transparency of clinical guideline updating for the benefit of patients and the public, health care professionals, and other relevant stakeholders. PMID:28072838

  19. Treatment response to olanzapine and haloperidol and its association with dopamine D receptor occupancy in first-episode psychosis.

    PubMed

    Zipursky, Robert B; Christensen, Bruce K; Daskalakis, Zafiris; Epstein, Irvin; Roy, Paul; Furimsky, Ivana; Sanger, Todd; Kapur, Shitij

    2005-07-01

    Response to typical antipsychotic medication has been associated with achieving a level of striatal dopamine D2 receptor occupancy in the range of 65% to 70%. We undertook this study to determine whether response to the atypical antipsychotic olanzapine occurs at lower levels of D2 receptor occupancy. Eighteen patients who presented with a first episode of psychosis were randomized to receive olanzapine 5 mg daily or haloperidol 2 mg daily in a double-blind design. We acquired positron emission tomography (PET) scans using the D2 ligand [11C]raclopride within the first 15 days of treatment to determine the percentage of D2 receptors occupied by the medication. According to response, dosage was then adjusted to a maximum dosage of 20 mg daily of either drug. PET scans were repeated after 10 to 12 weeks of treatment. At the first PET scan, the 8 olanzapine-treated patients had significantly lower D2 receptor occupancies (mean 63.4%, SD 7.3) than those observed in the 10 patients treated with haloperidol (mean 73.0%, SD 6.1). When patients were rescanned following dosage adjustment, mean D2 receptor occupancies were greater than 70% in both groups. D2 receptor occupancies did not differ significantly between the olanzapine-treated group (mean 72.0%, SD 5.7) and the haloperidol-treated group (mean 78.7%, SD 7.6). These results suggest that, in patients being treated for a first episode of psychosis, olanzapine has its antipsychotic effect at approximately the same levels of D2 receptor occupancy as are achieved with low dosages of haloperidol.

  20. An update on PPAR activation by cannabinoids

    PubMed Central

    2016-01-01

    Some cannabinoids activate the different isoforms of PPARs (α, β and γ), as shown through the use of reporter gene assays, binding studies, selective antagonists and knockout studies. Activation of all isoforms, but primarily PPARα and γ, mediates some (but not all) of the analgesic, neuroprotective, neuronal function modulation, anti‐inflammatory, metabolic, anti‐tumour, gastrointestinal and cardiovascular effects of some cannabinoids, often in conjunction with activation of the more traditional target sites of action such as the cannabinoid CB1 and CB2 receptors and the TRPV1 ion channel. PPARs also mediate some of the effects of inhibitors of endocannabinoid degradation or transport. Cannabinoids may be chaperoned to the PPARs by fatty acid binding proteins. The aims of this review are to update the evidence supporting PPAR activation by cannabinoids and to review the physiological responses to cannabinoids that are mediated, and not mediated, by PPAR activation. PMID:27077495

  1. Studying the Stoichiometry of Epidermal Growth Factor Receptor in Intact Cells using Correlative Microscopy.

    PubMed

    Peckys, Diana B; de Jonge, Niels

    2015-09-11

    This protocol describes the labeling of epidermal growth factor receptor (EGFR) on COS7 fibroblast cells, and subsequent correlative fluorescence microscopy and environmental scanning electron microscopy (ESEM) of whole cells in hydrated state. Fluorescent quantum dots (QDs) were coupled to EGFR via a two-step labeling protocol, providing an efficient and specific protein labeling, while avoiding label-induced clustering of the receptor. Fluorescence microscopy provided overview images of the cellular locations of the EGFR. The scanning transmission electron microscopy (STEM) detector was used to detect the QD labels with nanoscale resolution. The resulting correlative images provide data of the cellular EGFR distribution, and the stoichiometry at the single molecular level in the natural context of the hydrated intact cell. ESEM-STEM images revealed the receptor to be present as monomer, as homodimer, and in small clusters. Labeling with two different QDs, i.e., one emitting at 655 nm and at 800 revealed similar characteristic results.

  2. Nucleus Accumbens Acetylcholine Receptors Modulate Dopamine and Motivation.

    PubMed

    Collins, Anne L; Aitken, Tara J; Greenfield, Venuz Y; Ostlund, Sean B; Wassum, Kate M

    2016-11-01

    Environmental reward-predictive cues can motivate reward-seeking behaviors. Although this influence is normally adaptive, it can become maladaptive in disordered states, such as addiction. Dopamine release in the nucleus accumbens core (NAc) is known to mediate the motivational impact of reward-predictive cues, but little is known about how other neuromodulatory systems contribute to cue-motivated behavior. Here, we examined the role of the NAc cholinergic receptor system in cue-motivated behavior using a Pavlovian-to-instrumental transfer task designed to assess the motivating influence of a reward-predictive cue over an independently-trained instrumental action. Disruption of NAc muscarinic acetylcholine receptor activity attenuated, whereas blockade of nicotinic receptors augmented cue-induced invigoration of reward seeking. We next examined a potential dopaminergic mechanism for this behavioral effect by combining fast-scan cyclic voltammetry with local pharmacological acetylcholine receptor manipulation. The data show evidence of opposing modulation of cue-evoked dopamine release, with muscarinic and nicotinic receptor antagonists causing suppression and augmentation, respectively, consistent with the behavioral effects of these manipulations. In addition to demonstrating cholinergic modulation of naturally-evoked and behaviorally-relevant dopamine signaling, these data suggest that NAc cholinergic receptors may gate the expression of cue-motivated behavior through modulation of phasic dopamine release.

  3. Molecular and functional properties of P2X receptors--recent progress and persisting challenges.

    PubMed

    Kaczmarek-Hájek, Karina; Lörinczi, Eva; Hausmann, Ralf; Nicke, Annette

    2012-09-01

    ATP-gated P2X receptors are trimeric ion channels that assemble as homo- or heteromers from seven cloned subunits. Transcripts and/or proteins of P2X subunits have been found in most, if not all, mammalian tissues and are being discovered in an increasing number of non-vertebrates. Both the first crystal structure of a P2X receptor and the generation of knockout (KO) mice for five of the seven cloned subtypes greatly advanced our understanding of their molecular and physiological function and their validation as drug targets. This review summarizes the current understanding of the structure and function of P2X receptors and gives an update on recent developments in the search for P2X subtype-selective ligands. It also provides an overview about the current knowledge of the regulation and modulation of P2X receptors on the cellular level and finally on their physiological roles as inferred from studies on KO mice.

  4. Response phase mapping of nonlinear joint dynamics using continuous scanning LDV measurement method

    NASA Astrophysics Data System (ADS)

    Di Maio, D.; Bozzo, A.; Peyret, Nicolas

    2016-06-01

    This study aims to present a novel work aimed at locating discrete nonlinearities in mechanical assemblies. The long term objective is to develop a new metric for detecting and locating nonlinearities using Scanning LDV systems (SLDV). This new metric will help to improve the modal updating, or validation, of mechanical assemblies presenting discrete and sparse nonlinearities. It is well established that SLDV systems can scan vibrating structures with high density of measurement points and produc e highly defined Operational Deflection Shapes (ODSs). This paper will present some insights on how to use response phase mapping for locating nonlinearities of a bolted flange. This type of structure presents two types of nonlinearities, which are geometr ical and frictional joints. The interest is focussed on the frictional joints and, therefore, the ability to locate which joint s are responsible for nonlinearity is seen highly valuable for the model validation activities.

  5. Dissociating Working Memory Updating and Automatic Updating: The Reference-Back Paradigm

    ERIC Educational Resources Information Center

    Rac-Lubashevsky, Rachel; Kessler, Yoav

    2016-01-01

    Working memory (WM) updating is a controlled process through which relevant information in the environment is selected to enter the gate to WM and substitute its contents. We suggest that there is also an automatic form of updating, which influences performance in many tasks and is primarily manifested in reaction time sequential effects. The goal…

  6. Robust Adaptive Thresholder For Document Scanning Applications

    NASA Astrophysics Data System (ADS)

    Hsing, To R.

    1982-12-01

    In document scanning applications, thresholding is used to obtain binary data from a scanner. However, due to: (1) a wide range of different color backgrounds; (2) density variations of printed text information; and (3) the shading effect caused by the optical systems, the use of adaptive thresholding to enhance the useful information is highly desired. This paper describes a new robust adaptive thresholder for obtaining valid binary images. It is basically a memory type algorithm which can dynamically update the black and white reference level to optimize a local adaptive threshold function. The results of high image quality from different types of simulate test patterns can be obtained by this algorithm. The software algorithm is described and experiment results are present to describe the procedures. Results also show that the techniques described here can be used for real-time signal processing in the varied applications.

  7. An update on PPAR activation by cannabinoids.

    PubMed

    O'Sullivan, Saoirse Elizabeth

    2016-06-01

    Some cannabinoids activate the different isoforms of PPARs (α, β and γ), as shown through the use of reporter gene assays, binding studies, selective antagonists and knockout studies. Activation of all isoforms, but primarily PPARα and γ, mediates some (but not all) of the analgesic, neuroprotective, neuronal function modulation, anti-inflammatory, metabolic, anti-tumour, gastrointestinal and cardiovascular effects of some cannabinoids, often in conjunction with activation of the more traditional target sites of action such as the cannabinoid CB1 and CB2 receptors and the TRPV1 ion channel. PPARs also mediate some of the effects of inhibitors of endocannabinoid degradation or transport. Cannabinoids may be chaperoned to the PPARs by fatty acid binding proteins. The aims of this review are to update the evidence supporting PPAR activation by cannabinoids and to review the physiological responses to cannabinoids that are mediated, and not mediated, by PPAR activation. © 2016 The British Pharmacological Society.

  8. Fast scanning mode and its realization in a scanning acoustic microscope

    NASA Astrophysics Data System (ADS)

    Ju, Bing-Feng; Bai, Xiaolong; Chen, Jian

    2012-03-01

    The scanning speed of the two-dimensional stage dominates the efficiency of mechanical scanning measurement systems. This paper focused on a detailed scanning time analysis of conventional raster and spiral scan modes and then proposed two fast alternative scanning modes. Performed on a self-developed scanning acoustic microscope (SAM), the measured images obtained by using the conventional scan mode and fast scan modes are compared. The total scanning time is reduced by 29% of the two proposed fast scan modes. It will offer a better solution for high speed scanning without sacrificing the system stability, and will not introduce additional difficulties to the configuration of scanning measurement systems. They can be easily applied to the mechanical scanning measuring systems with different driving actuators such as piezoelectric, linear motor, dc motor, and so on. The proposed fast raster and square spiral scan modes are realized in SAM, but not specially designed for it. Therefore, they have universal adaptability and can be applied to other scanning measurement systems with two-dimensional mechanical scanning stages, such as atomic force microscope or scanning tunneling microscope.

  9. Unconventional binding sites and receptors for VIP and related peptides PACAP and PHI/PHM: an update.

    PubMed

    Muller, Jean-Marc; Debaigt, Colin; Goursaud, Stéphanie; Montoni, Alicia; Pineau, Nicolas; Meunier, Annie-Claire; Janet, Thierry

    2007-09-01

    The 28-amino-acid neuropeptide VIP and related peptides PACAP and PHI/PHM modulate virtually all of the vital functions in the body. These peptides are also commonly recognized as major regulators of cell growth and differentiation. Through their trophic and cytoprotective functions, they appear to play major roles in embryonic development, neurogenesis and the progression of a number of cancer types. These peptides bind to three well-characterized subtypes of G-protein coupled receptors: VPAC1 and VPAC2 share a common high affinity in the nanomolar range for VIP and PACAP; a third receptor type, PAC1, has been characterized for its high affinity for PACAP but its low affinity for VIP. Complex effects and pharmacological behaviors of these peptides suggest that multiple subtypes of binding sites may cooperate to mediate their function in target cells and tissues. In this complex response, some of these binding sites correspond to the definition of the conventional receptors cited above, while others display unexpected pharmacological and functional properties. Here we present potential clues that may lead investigators to further characterize the molecular nature and functions of these atypical binding species.

  10. Pelvic CT scan

    MedlinePlus

    CAT scan - pelvis; Computed axial tomography scan - pelvis; Computed tomography scan - pelvis; CT scan - pelvis ... Risks of CT scans include: Being exposed to radiation Allergic reaction to contrast dye CT scans do expose you to more radiation ...

  11. Shoulder CT scan

    MedlinePlus

    CAT scan - shoulder; Computed axial tomography scan - shoulder; Computed tomography scan - shoulder; CT scan - shoulder ... Risks of CT scans include: Being exposed to radiation Allergic reaction to contrast dye Birth defect if done during pregnancy CT scans ...

  12. Sinus CT scan

    MedlinePlus

    CAT scan - sinus; Computed axial tomography scan - sinus; Computed tomography scan - sinus; CT scan - sinus ... Risks for a CT scan includes: Being exposed to radiation Allergic reaction to contrast dye CT scans expose you to more radiation than regular ...

  13. ScanImage: flexible software for operating laser scanning microscopes.

    PubMed

    Pologruto, Thomas A; Sabatini, Bernardo L; Svoboda, Karel

    2003-05-17

    Laser scanning microscopy is a powerful tool for analyzing the structure and function of biological specimens. Although numerous commercial laser scanning microscopes exist, some of the more interesting and challenging applications demand custom design. A major impediment to custom design is the difficulty of building custom data acquisition hardware and writing the complex software required to run the laser scanning microscope. We describe a simple, software-based approach to operating a laser scanning microscope without the need for custom data acquisition hardware. Data acquisition and control of laser scanning are achieved through standard data acquisition boards. The entire burden of signal integration and image processing is placed on the CPU of the computer. We quantitate the effectiveness of our data acquisition and signal conditioning algorithm under a variety of conditions. We implement our approach in an open source software package (ScanImage) and describe its functionality. We present ScanImage, software to run a flexible laser scanning microscope that allows easy custom design.

  14. Line-scanning, stage scanning confocal microscope

    NASA Astrophysics Data System (ADS)

    Carucci, John A.; Stevenson, Mary; Gareau, Daniel

    2016-03-01

    We created a line-scanning, stage scanning confocal microscope as part of a new procedure: video assisted micrographic surgery (VAMS). The need for rapid pathological assessment of the tissue on the surface of skin excisions very large since there are 3.5 million new skin cancers diagnosed annually in the United States. The new design presented here is a confocal microscope without any scanning optics. Instead, a line is focused in space and the sample, which is flattened, is physically translated such that the line scans across its face in a direction perpendicular to the line its self. The line is 6mm long and the stage is capable of scanning 50 mm, hence the field of view is quite large. The theoretical diffraction-limited resolution is 0.7um lateral and 3.7um axial. However, in this preliminary report, we present initial results that are a factor of 5-7 poorer in resolution. The results are encouraging because they demonstrate that the linear array detector measures sufficient signal from fluorescently labeled tissue and also demonstrate the large field of view achievable with VAMS.

  15. Review and update of mutations causing Waardenburg syndrome.

    PubMed

    Pingault, Véronique; Ente, Dorothée; Dastot-Le Moal, Florence; Goossens, Michel; Marlin, Sandrine; Bondurand, Nadège

    2010-04-01

    Waardenburg syndrome (WS) is characterized by the association of pigmentation abnormalities, including depigmented patches of the skin and hair, vivid blue eyes or heterochromia irides, and sensorineural hearing loss. However, other features such as dystopia canthorum, musculoskeletal abnormalities of the limbs, Hirschsprung disease, or neurological defects are found in subsets of patients and used for the clinical classification of WS. Six genes are involved in this syndrome: PAX3 (encoding the paired box 3 transcription factor), MITF (microphthalmia-associated transcription factor), EDN3 (endothelin 3), EDNRB (endothelin receptor type B), SOX10 (encoding the Sry bOX10 transcription factor), and SNAI2 (snail homolog 2), with different frequencies. In this review we provide an update on all WS genes and set up mutation databases, summarize molecular and functional data available for each of them, and discuss the applications in diagnostics and genetic counseling. (c) 2010 Wiley-Liss, Inc.

  16. Thyroid scan

    MedlinePlus

    ... thyroid; Radioactive iodine uptake and scan test - thyroid; Nuclear scan - thyroid ... the test. Ask your provider or the radiology/nuclear medicine team performing the scan about taking precautions.

  17. Vitamin D receptor genetic polymorphisms and tuberculosis: updated systematic review and meta-analysis.

    PubMed

    Gao, L; Tao, Y; Zhang, L; Jin, Q

    2010-01-01

    Host genetic susceptibility has been suggested as one of the most important explanations for inter-individual differences in tuberculosis (TB) risk. The vitamin D receptor (VDR) gene has been studied as a candidate locus due to genetic polymorphisms that affects the activity of the receptor and subsequent downstream vitamin D-mediated effects. We reviewed published studies on VDR polymorphisms and TB susceptibility up to 15 April 2009 and quantitatively summarised associations of the most widely studied polymorphisms (FokI, TaqI, ApaI and BsmI) using meta-analysis. A total of 23 eligible studies were included in this review. Heterogeneous results were observed, which may be partly explained by the differences between populations. Among Asians, the FokI ff genotype showed a pronounced positive association (OR 2.0, 95%CI 1.3-3.2), a significant inverse association was observed for the BsmI bb genotype (OR 0.5, 95%CI 0.4-0.8), and marginal significant associations were found for TaqI and ApaI polymorphisms. However, none of the polymorphisms was significantly related to TB among Africans or South Americans. The association of VDR polymorphisms with risk of TB observed in our analyses supports the hypothesis that vitamin D deficiency might play a role as risk factor during the development of TB.

  18. An interchangeable scanning Hall probe/scanning SQUID microscope

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Tang, Chiu-Chun; Lin, Hui-Ting; Wu, Sing-Lin

    2014-08-15

    We have constructed a scanning probe microscope for magnetic imaging, which can function as a scanning Hall probe microscope (SHPM) and as a scanning SQUID microscope (SSM). The scanning scheme, applicable to SHPM and SSM, consists of a mechanical positioning (sub) micron-XY stage and a flexible direct contact to the sample without a feedback control system for the Z-axis. With the interchangeable capability of operating two distinct scanning modes, our microscope can incorporate the advantageous functionalities of the SHPM and SSM with large scan range up to millimeter, high spatial resolution (⩽4 μm), and high field sensitivity in a widemore » range of temperature (4.2 K-300 K) and magnetic field (10{sup −7} T-1 T). To demonstrate the capabilities of the system, we present magnetic images scanned with SHPM and SSM, including a RbFeB magnet and a nickel grid pattern at room temperature, surface magnetic domain structures of a La{sub 2/3}Ca{sub 1/3}MnO{sub 3} thin film at 77 K, and superconducting vortices in a striped niobium film at 4.2 K.« less

  19. Updating of working memory: lingering bindings.

    PubMed

    Oberauer, Klaus; Vockenberg, Kerstin

    2009-05-01

    Three experiments investigated proactive interference and proactive facilitation in a memory-updating paradigm. Participants remembered several letters or spatial patterns, distinguished by their spatial positions, and updated them by new stimuli up to 20 times per trial. Self-paced updating times were shorter when an item previously remembered and then replaced reappeared in the same location than when it reappeared in a different location. This effect demonstrates residual memory for no-longer-relevant bindings of items to locations. The effect increased with the number of items to be remembered. With one exception, updating times did not increase, and recall of final values did not decrease, over successive updating steps, thus providing little evidence for proactive interference building up cumulatively.

  20. Lack of Set Size Effects in Spatial Updating: Evidence for Offline Updating

    ERIC Educational Resources Information Center

    Hodgson, Eric; Waller, David

    2006-01-01

    Four experiments required participants to keep track of the locations of (i.e., update) 1, 2, 3, 4, 6, 8, 10, or 15 target objects after rotating. Across all conditions, updating was unaffected by set size. Although some traditional set size effects (i.e., a linear increase of latency with memory load) were observed under some conditions, these…

  1. Leg CT scan

    MedlinePlus

    CAT scan - leg; Computed axial tomography scan - leg; Computed tomography scan - leg; CT scan - leg ... CT scan makes detailed pictures of the body very quickly. The test may help look for: An abscess ...

  2. Arm CT scan

    MedlinePlus

    CAT scan - arm; Computed axial tomography scan - arm; Computed tomography scan - arm; CT scan - arm ... Healing problems or scar tissue following surgery A CT scan may also be used to guide a surgeon ...

  3. 49 CFR 1002.3 - Updating user fees.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... updating fees. Each fee shall be updated by updating the cost components comprising the fee. Cost... direct labor costs are direct labor costs determined by the cost study set forth in Revision of Fees For... by total office costs for the Offices directly associated with user fee activity. Actual updating of...

  4. Orion recovery test update on This Week @NASA - August 8, 2014

    NASA Image and Video Library

    2014-08-08

    NASA wrapped up its second Underway Recovery Test Aug. 4 with the Orion spacecraft, off the coast of San Diego, California. The agency teamed with Lockheed Martin, the U.S. Navy and the Department of Defense's Human Space Flight Support Detachment 3 to evaluate primary and alternative methods to recover Orion after the spacecraft safely splashes down in the ocean at the conclusion of future deep space missions. Orion’s first spaceflight test with a splashdown in the Pacific Ocean is targeted for December. Also, Low-Density Supersonic Decelerator update, 2nd anniversary: 7 Minutes of Terror, Bolden visits MMS at Naval Research Lab, Scanning for algal blooms, Earth science showcase, and more!

  5. Nuclear Scans

    MedlinePlus

    Nuclear scans use radioactive substances to see structures and functions inside your body. They use a special ... images. Most scans take 20 to 45 minutes. Nuclear scans can help doctors diagnose many conditions, including ...

  6. International Union of Pharmacology LVIII: Update on the P2Y G Protein-Coupled Nucleotide Receptors: From Molecular Mechanisms and Pathophysiology to Therapy

    PubMed Central

    ABBRACCHIO, MARIA P.; BURNSTOCK, GEOFFREY; BOEYNAEMS, JEAN-MARIE; BARNARD, ERIC A.; BOYER, JOSÉ L.; KENNEDY, CHARLES; KNIGHT, GILLIAN E.; FUMAGALLI, MARTA; GACHET, CHRISTIAN; JACOBSON, KENNETH A.; WEISMAN, GARY A.

    2012-01-01

    There have been many advances in our knowledge about different aspects of P2Y receptor signaling since the last review published by our International Union of Pharmacology subcommittee. More receptor subtypes have been cloned and characterized and most orphan receptors deorphanized, so that it is now possible to provide a basis for a future subdivision of P2Y receptor subtypes. More is known about the functional elements of the P2Y receptor molecules and the signaling pathways involved, including interactions with ion channels. There have been substantial developments in the design of selective agonists and antagonists to some of the P2Y receptor subtypes. There are new findings about the mechanisms underlying nucleotide release and ectoenzymatic nucleotide breakdown. Interactions between P2Y receptors and receptors to other signaling molecules have been explored as well as P2Y-mediated control of gene transcription. The distribution and roles of P2Y receptor subtypes in many different cell types are better understood and P2Y receptor-related compounds are being explored for therapeutic purposes. These and other advances are discussed in the present review. PMID:16968944

  7. Country Update: Israel 2005

    ERIC Educational Resources Information Center

    Marar, Marianne Maurice

    2005-01-01

    Country Updates is a new section of "Intercultural Education." Starting in "Intercultural Education," Volume 16 No. 5, this column will focus on recent developments during the last two to three years in the field of intercultural education in one particular country. These updates can include recent policy decisions, the main…

  8. An update on gain-of-function mutations in primary immunodeficiency diseases.

    PubMed

    Jhamnani, Rekha D; Rosenzweig, Sergio D

    2017-12-01

    Most primary immunodeficiencies described since 1952 were associated with loss-of-function defects. With the advent and popularization of unbiased next-generation sequencing diagnostic approaches followed by functional validation techniques, many gain-of-function mutations leading to immunodeficiency have also been identified. This review highlights the updates on pathophysiology mechanisms and new therapeutic approaches involving primary immunodeficiencies because of gain-of-function mutations. The more recent developments related to gain-of-function primary immunodeficiencies mostly involving increased infection susceptibility but also immune dysregulation and autoimmunity, were reviewed. Updates regarding pathophysiology mechanisms, different mutation types, clinical features, laboratory markers, current and potential new treatments on patients with caspase recruitment domain family member 11, signal transducer and activator of transcription 1, signal transducer and activator of transcription 3, phosphatidylinositol-4,5-biphosphate 3-kinase catalytic 110, phosphatidylinositol-4,5-biphosphate 3-kinase regulatory subunit 1, chemokine C-X-C motif receptor 4, sterile α motif domain containing 9-like, and nuclear factor κ-B subunit 2 gain-of-function mutations are reviewed for each disease. With the identification of gain-of-function mutations as a cause of immunodeficiency, new genetic pathophysiology mechanisms unveiled and new-targeted therapeutic approaches can be explored as potential rescue treatments for these diseases.

  9. 78 FR 51073 - Product List Update

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-08-20

    ... POSTAL REGULATORY COMMISSION 39 CFR Part 3020 [Docket Nos. MC2012-49, et al.] Product List Update... competitive product list. This action reflects the disposition of recent dockets, as reflected in Commission... updates. The updates are identified in the body of this document. The product lists, which are republished...

  10. Head CT scan

    MedlinePlus

    Brain CT; Cranial CT; CT scan - skull; CT scan - head; CT scan - orbits; CT scan - sinuses; Computed tomography - cranial; CAT scan - brain ... conditions: Birth (congenital) defect of the head or brain Brain infection Brain tumor Buildup of fluid inside ...

  11. Mechanisms of Kappa Opioid Receptor Potentiation of Dopamine D2 Receptor Function in Quinpirole-Induced Locomotor Sensitization in Rats.

    PubMed

    Escobar, Angélica P; González, Marcela P; Meza, Rodrigo C; Noches, Verónica; Henny, Pablo; Gysling, Katia; España, Rodrigo A; Fuentealba, José A; Andrés, María E

    2017-08-01

    Increased locomotor activity in response to the same stimulus is an index of behavioral sensitization observed in preclinical models of drug addiction and compulsive behaviors. Repeated administration of quinpirole, a D2/D3 dopamine agonist, induces locomotor sensitization. This effect is potentiated and accelerated by co-administration of U69593, a kappa opioid receptor agonist. The mechanism underlying kappa opioid receptor potentiation of quinpirole-induced locomotor sensitization remains to be elucidated. Immunofluorescence anatomical studies were undertaken in mice brain slices and rat presynaptic synaptosomes to reveal kappa opioid receptor and D2R pre- and postsynaptic colocalization in the nucleus accumbens. Tonic and phasic dopamine release in the nucleus accumbens of rats repeatedly treated with U69593 and quinpirole was assessed by microdialysis and fast scan cyclic voltammetry. Anatomical data show that kappa opioid receptor and D2R colocalize postsynaptically in medium spiny neurons of the nucleus accumbens and the highest presynaptic colocalization occurs on the same dopamine terminals. Significantly reduced dopamine levels were observed in quinpirole, and U69593-quinpirole treated rats, explaining sensitization of D2R. Presynaptic inhibition induced by kappa opioid receptor and D2R of electrically evoked dopamine release was faster in U69593-quinpirole compared with quinpirole-repeatedly treated rats. Pre- and postsynaptic colocalization of kappa opioid receptor and D2R supports a role for kappa opioid receptor potentiating both the D2R inhibitory autoreceptor function and the inhibitory action of D2R on efferent medium spiny neurons. Kappa opioid receptor co-activation accelerates D2R sensitization by contributing to decrease dopamine release in the nucleus accumbens. © The Author 2017. Published by Oxford University Press on behalf of CINP.

  12. Recommendations for Human Epidermal Growth Factor Receptor 2 Testing in Breast Cancer

    PubMed Central

    Wolff, Antonio C.; Hammond, M. Elizabeth H.; Hicks, David G.; Dowsett, Mitch; McShane, Lisa M.; Allison, Kimberly H.; Allred, Donald C.; Bartlett, John M.S.; Bilous, Michael; Fitzgibbons, Patrick; Hanna, Wedad; Jenkins, Robert B.; Mangu, Pamela B.; Paik, Soonmyung; Perez, Edith A.; Press, Michael F.; Spears, Patricia A.; Vance, Gail H.; Viale, Giuseppe; Hayes, Daniel F.

    2014-01-01

    Purpose To update the American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guideline recommendations for human epidermal growth factor receptor 2 (HER2) testing in breast cancer to improve the accuracy of HER2 testing and its utility as a predictive marker in invasive breast cancer. Methods ASCO/CAP convened an Update Committee that included coauthors of the 2007 guideline to conduct a systematic literature review and update recommendations for optimal HER2 testing. Results The Update Committee identified criteria and areas requiring clarification to improve the accuracy of HER2 testing by immunohistochemistry (IHC) or in situ hybridization (ISH). The guideline was reviewed and approved by both organizations. Recommendations The Update Committee recommends that HER2 status (HER2 negative or positive) be determined in all patients with invasive (early stage or recurrence) breast cancer on the basis of one or more HER2 test results (negative, equivocal, or positive). Testing criteria define HER2-positive status when (on observing within an area of tumor that amounts to >10% of contiguous and homogeneous tumor cells) there is evidence of protein overexpression (IHC) or gene amplification (HER2 copy number or HER2/CEP17 ratio by ISH based on counting at least 20 cells within the area). If results are equivocal (revised criteria), reflex testing should be performed using an alternative assay (IHC or ISH). Repeat testing should be considered if results seem discordant with other histopathologic findings. Laboratories should demonstrate high concordance with a validated HER2 test on a sufficiently large and representative set of specimens. Testing must be performed in a laboratory accredited by CAP or another accrediting entity. The Update Committee urges providers and health systems to cooperate to ensure the highest quality testing. PMID:24099077

  13. SERC 2014 2018 Technical Plan: 2016 Update

    DTIC Science & Technology

    2016-02-18

    Contract Number: HQ0034-13-D-0004 February 18, 2016 SERC 2014-2018 Technical Plan Update SERC 2014-2018 Technical Plan: 2016 Update...UNCLASSIFIED / APPROVED FOR PUBLIC RELEASE Contract Number: HQ0034-13-D-0004 February 18, 2016 SERC 2014-2018 Technical Plan Update ii...18, 2016 SERC 2014-2018 Technical Plan Update iii TABLE OF CONTENTS Table of Contents

  14. A Probabilistic Approach to Model Update

    NASA Technical Reports Server (NTRS)

    Horta, Lucas G.; Reaves, Mercedes C.; Voracek, David F.

    2001-01-01

    Finite element models are often developed for load validation, structural certification, response predictions, and to study alternate design concepts. In rare occasions, models developed with a nominal set of parameters agree with experimental data without the need to update parameter values. Today, model updating is generally heuristic and often performed by a skilled analyst with in-depth understanding of the model assumptions. Parameter uncertainties play a key role in understanding the model update problem and therefore probabilistic analysis tools, developed for reliability and risk analysis, may be used to incorporate uncertainty in the analysis. In this work, probability analysis (PA) tools are used to aid the parameter update task using experimental data and some basic knowledge of potential error sources. Discussed here is the first application of PA tools to update parameters of a finite element model for a composite wing structure. Static deflection data at six locations are used to update five parameters. It is shown that while prediction of individual response values may not be matched identically, the system response is significantly improved with moderate changes in parameter values.

  15. 34 CFR 668.55 - Updating information.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... information to be updated has taken place since the last update. (3) If, as a result of a change in the... section apply, an applicant is required to update— (i) The number of family members in the applicant's... changes, the applicant shall not update those factors or that status. (b) If the number of family members...

  16. Rapid and Adaptable Measurement of Protein Thermal Stability by Differential Scanning Fluorimetry: Updating a Common Biochemical Laboratory Experiment

    ERIC Educational Resources Information Center

    Johnson, R. Jeremy; Savas, Christopher J.; Kartje, Zachary; Hoops, Geoffrey C.

    2014-01-01

    Measurement of protein denaturation and protein folding is a common laboratory technique used in undergraduate biochemistry laboratories. Differential scanning fluorimetry (DSF) provides a rapid, sensitive, and general method for measuring protein thermal stability in an undergraduate biochemistry laboratory. In this method, the thermal…

  17. Synthesis and Evaluation of Radioligands for Imaging Brain Nociceptin/Orphanin FQ Peptide (NOP) Receptors with Positron Emission Tomography

    PubMed Central

    Pike, Victor W.; Rash, Karen S.; Chen, Zhaogen; Pedregal, Concepción; Statnick, Michael A.; Kimura, Yasuyuki; Hong, Jinsoo; Zoghbi, Sami S.; Fujita, Masahiro; Toledo, Miguel A.; Diaz, Nuria; Gackenheimer, Susan L.; Tauscher, Johannes T.; Barth, Vanessa N.; Innis, Robert B.

    2011-01-01

    Positron emission tomography (PET) coupled to an effective radioligand could provide an important tool for understanding possible links between neuropsychiatric disorders and brain NOP (nociceptin/orphanin FQ peptide) receptors. We sought to develop such a PET radioligand. High-affinity NOP ligands were synthesized based on a 3-(2'-fluoro-4',5'-dihydrospiro[piperidine-4,7'-thieno[2,3-c]pyran]-1-yl)-2(2-halobenzyl)-N-alkylpropanamide scaffold and from experimental screens in rats, with ex vivo LC-MS/MS measures, three ligands were identified for labeling with carbon-11 and evaluation with PET in monkey. Each ligand was labeled by 11C-methylation of an N-desmethyl precursor and studied in monkey under baseline and NOP receptor-preblock conditions. The three radioligands, [11C](S)-10a–c, gave similar results. Baseline scans showed high entry of radioactivity into brain to give a distribution reflecting that expected for NOP receptors. Pre-block experiments showed high early peak levels of brain radioactivity which rapidly declined to a much lower level than seen in baseline scans, thereby indicating a high level of receptor-specific binding in baseline experiments. Overall, [11C](S)-10c showed the most favorable receptor-specific signal and kinetics and is now selected for evaluation in human subjects. PMID:21438532

  18. BI-RADS update.

    PubMed

    Mercado, Cecilia L

    2014-05-01

    The updated American College of Radiology (ACR) Breast Imaging Reporting and Data System (BI-RADS) has been newly released. This article summarizes the changes and updates that have been made to BI-RADS. The goal of the revised edition continues to be the same: to improve clarification in image interpretation, maintain reporting standardization, and simplify the monitoring of outcomes. The new BI-RADS also introduces new terminology to provide a more universal lexicon across all 3 imaging modalities. Copyright © 2014 Elsevier Inc. All rights reserved.

  19. Calcitonin and Amylin Receptor Peptide Interaction Mechanisms: INSIGHTS INTO PEPTIDE-BINDING MODES AND ALLOSTERIC MODULATION OF THE CALCITONIN RECEPTOR BY RECEPTOR ACTIVITY-MODIFYING PROTEINS.

    PubMed

    Lee, Sang-Min; Hay, Debbie L; Pioszak, Augen A

    2016-04-15

    Receptor activity-modifying proteins (RAMP1-3) determine the selectivity of the class B G protein-coupled calcitonin receptor (CTR) and the CTR-like receptor (CLR) for calcitonin (CT), amylin (Amy), calcitonin gene-related peptide (CGRP), and adrenomedullin (AM) peptides. RAMP1/2 alter CLR selectivity for CGRP/AM in part by RAMP1 Trp-84 or RAMP2 Glu-101 contacting the distinct CGRP/AM C-terminal residues. It is unclear whether RAMPs use a similar mechanism to modulate CTR affinity for CT and Amy, analogs of which are therapeutics for bone disorders and diabetes, respectively. Here, we reproduced the peptide selectivity of intact CTR, AMY1 (CTR·RAMP1), and AMY2 (CTR·RAMP2) receptors using purified CTR extracellular domain (ECD) and tethered RAMP1- and RAMP2-CTR ECD fusion proteins and antagonist peptides. All three proteins bound salmon calcitonin (sCT). Tethering RAMPs to CTR enhanced binding of rAmy, CGRP, and the AMY antagonist AC413. Peptide alanine-scanning mutagenesis and modeling of receptor-bound sCT and AC413 supported a shared non-helical CGRP-like conformation for their TN(T/V)G motif prior to the C terminus. After this motif, the peptides diverged; the sCT C-terminal Pro was crucial for receptor binding, whereas the AC413/rAmy C-terminal Tyr had little or no influence on binding. Accordingly, mutant RAMP1 W84A- and RAMP2 E101A-CTR ECD retained AC413/rAmy binding. ECD binding and cell-based signaling assays with antagonist sCT/AC413/rAmy variants with C-terminal residue swaps indicated that the C-terminal sCT/rAmy residue identity affects affinity more than selectivity. rAmy(8-37) Y37P exhibited enhanced antagonism of AMY1 while retaining selectivity. These results reveal unexpected differences in how RAMPs determine CTR and CLR peptide selectivity and support the hypothesis that RAMPs allosterically modulate CTR peptide affinity. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  20. Update on montelukast and its role in the treatment of asthma, allergic rhinitis and exercise-induced bronchoconstriction.

    PubMed

    Storms, William

    2007-09-01

    Montelukast sodium (Singulair, Merck and Co., Inc., Whitehouse Station, NJ) is a selective and orally-active leukotriene receptor antagonist with demonstrated effectiveness for treating allergic asthma and allergic rhinitis in adults and children as young as 12 months of age for allergic asthma and 6 months of age for allergic rhinitis. It was recently approved in the US for prevention of exercise-induced bronchoconstriction in patients who are > or = 15 years of age. This paper updates a prior review of the data on the clinical efficacy of montelukast published in this journal.

  1. Capital update factor: a new era approaches.

    PubMed

    Grimaldi, P L

    1993-02-01

    The Health Care Financing Administration (HCFA) has constructed a preliminary model of a new capital update method which is consistent with the framework being developed to refine the update method for PPS operating costs. HCFA's eventual goal is to develop a single update framework for operating and capital costs. Initial results suggest that adopting the new capital update method would reduce capital payments substantially, which might intensify creditor's concerns about extending loans to hospitals.

  2. The updated billion-ton resource assessment

    Treesearch

    Anthony Turhollow; Robert Perlack; Laurence Eaton; Matthew Langholtz; Craig Brandt; Mark Downing; Lynn Wright; Kenneth Skog; Chad Hellwinckel; Bryce Stokes; Patricia Lebow

    2014-01-01

    This paper summarizes the results of an update to a resource assessment, published in 2005, commonly referred to as the Billion-Ton Study (BTS). The updated results are consistent with the 2005 BTS in terms of overall magnitude. The 2005 BTS projected between 860 and 1240 Tg of biomass available in the 2050 timeframe, while the Billion-Ton Update (BT2), for a price of...

  3. Evaluation in Monkey of Two Candidate PET Radioligands, [11C]RX-1 and [18F]RX-2, for Imaging Brain 5-HT4 Receptors

    PubMed Central

    LOHITH, TALAKAD G.; XU, RONG; TSUJIKAWA, TETSUYA; MORSE, CHERYL L.; ANDERSON, KACEY B.; GLADDING, ROBERT L.; ZOGHBI, SAMI S.; FUJITA, MASAHIRO; INNIS, ROBERT B.; PIKE, VICTOR W.

    2014-01-01

    The serotonin subtype-4 (5-HT4) receptor, which is known to be involved physiologically in learning and memory, and pathologically in Alzheimer’s disease, anxiety and other neuropsychiatric disorders – has few radioligands readily available for imaging in vivo. We have previously reported two novel 5-HT4 receptor radioligands, namely [methoxy-11C](1-butylpiperidin-4-yl)methyl 4-amino-3-methoxybenzoate; [11C]RX-1) and the [18F]3-fluoromethoxy analog ([18F]RX-2), and in this study we evaluated them by PET in rhesus monkey. Brain scans were performed at baseline, receptor preblock or displacement conditions using SB 207710, a 5-HT4 receptor antagonist, on the same day for [11C]RX-1 and on different days for [18F]RX-2. Specific-to-nondisplaceable ratio (BPND) was measured with the simplified reference tissue model from all baseline scans. To determine specific binding, total distribution volume (VT) was also measured in some monkeys by radiometabolite-corrected arterial input function after ex vivo inhibition of esterases from baseline and blocked scans. Both radioligands showed moderate to high peak brain uptake of radioactivity (2–6 SUV). Regional BPND values were in the rank order of known 5-HT4 receptor distribution with a trend for higher BPND values from [18F]RX-2. One-tissue compartmental model provided good fits with well identified VT values for both radioligands. In the highest 5-HT4 receptor density region, striatum, 50–60% of total binding was specific. The VT in receptor-poor cerebellum reached stable values by about 60 min for both radioligands indicating little influence of radiometabolites on brain signal. In conclusion, both [11C]RX-1 and [18F]RX-2 showed positive attributes for PET imaging of brain 5-HT4 receptors, validating the radioligand design strategy. PMID:25088028

  4. Effectiveness and usability of Scanning Wizard software: a tool for enhancing switch scanning.

    PubMed

    Koester, Heidi Horstmann; Simpson, Richard C

    2017-11-24

    Scanning Wizard software helps scanning users improve the setup of their switch and scanning system. This study evaluated Scanning Wizard's effectiveness and usability. Ten people who use switch scanning and ten practitioners used Scanning Wizard in the initial session. Usability was high, based on survey responses averaging over 4.5 out of 5, and qualitative feedback was very positive. Five switch users were able to complete the multi-week protocol, using settings on their own scanning system that were recommended from the Scanning Wizard session. Using these revised settings, text entry rates improved by an average of 71%, ranging from 29% to 172% improvement. Results suggest that Scanning Wizard is a useful tool for improving the configuration of scanning systems for people who use switch scanning to communicate. Implications for Rehabilitation Some individuals with severe physical impairments use switch scanning for spoken and written communication. Scanning Wizard software helps scanning users improve the setup of their switch and scanning system. This study demonstrated high usability of Scanning Wizard (with 10 switch userpractitioner teams) and increased text entry rate by an average of 71% (for five switch users). Results suggest that Scanning Wizard is a useful tool for improving the configuration of scanning systems for people who use switch scanning to communicate.

  5. Optimal updating magnitude in adaptive flat-distribution sampling

    NASA Astrophysics Data System (ADS)

    Zhang, Cheng; Drake, Justin A.; Ma, Jianpeng; Pettitt, B. Montgomery

    2017-11-01

    We present a study on the optimization of the updating magnitude for a class of free energy methods based on flat-distribution sampling, including the Wang-Landau (WL) algorithm and metadynamics. These methods rely on adaptive construction of a bias potential that offsets the potential of mean force by histogram-based updates. The convergence of the bias potential can be improved by decreasing the updating magnitude with an optimal schedule. We show that while the asymptotically optimal schedule for the single-bin updating scheme (commonly used in the WL algorithm) is given by the known inverse-time formula, that for the Gaussian updating scheme (commonly used in metadynamics) is often more complex. We further show that the single-bin updating scheme is optimal for very long simulations, and it can be generalized to a class of bandpass updating schemes that are similarly optimal. These bandpass updating schemes target only a few long-range distribution modes and their optimal schedule is also given by the inverse-time formula. Constructed from orthogonal polynomials, the bandpass updating schemes generalize the WL and Langfeld-Lucini-Rago algorithms as an automatic parameter tuning scheme for umbrella sampling.

  6. Optimal updating magnitude in adaptive flat-distribution sampling.

    PubMed

    Zhang, Cheng; Drake, Justin A; Ma, Jianpeng; Pettitt, B Montgomery

    2017-11-07

    We present a study on the optimization of the updating magnitude for a class of free energy methods based on flat-distribution sampling, including the Wang-Landau (WL) algorithm and metadynamics. These methods rely on adaptive construction of a bias potential that offsets the potential of mean force by histogram-based updates. The convergence of the bias potential can be improved by decreasing the updating magnitude with an optimal schedule. We show that while the asymptotically optimal schedule for the single-bin updating scheme (commonly used in the WL algorithm) is given by the known inverse-time formula, that for the Gaussian updating scheme (commonly used in metadynamics) is often more complex. We further show that the single-bin updating scheme is optimal for very long simulations, and it can be generalized to a class of bandpass updating schemes that are similarly optimal. These bandpass updating schemes target only a few long-range distribution modes and their optimal schedule is also given by the inverse-time formula. Constructed from orthogonal polynomials, the bandpass updating schemes generalize the WL and Langfeld-Lucini-Rago algorithms as an automatic parameter tuning scheme for umbrella sampling.

  7. 10 CFR 72.70 - Safety analysis report updating.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... original FSAR or, as appropriate, the last update to the FSAR under this section. The update shall include... for an ISFSI or MRS shall update periodically, as provided in paragraphs (b) and (c) of this section... applicant commitments developed during the license approval and/or hearing process. (b) Each update shall...

  8. 10 CFR 72.70 - Safety analysis report updating.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... original FSAR or, as appropriate, the last update to the FSAR under this section. The update shall include... for an ISFSI or MRS shall update periodically, as provided in paragraphs (b) and (c) of this section... applicant commitments developed during the license approval and/or hearing process. (b) Each update shall...

  9. 10 CFR 72.70 - Safety analysis report updating.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... original FSAR or, as appropriate, the last update to the FSAR under this section. The update shall include... for an ISFSI or MRS shall update periodically, as provided in paragraphs (b) and (c) of this section... applicant commitments developed during the license approval and/or hearing process. (b) Each update shall...

  10. 10 CFR 72.70 - Safety analysis report updating.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... original FSAR or, as appropriate, the last update to the FSAR under this section. The update shall include... for an ISFSI or MRS shall update periodically, as provided in paragraphs (b) and (c) of this section... applicant commitments developed during the license approval and/or hearing process. (b) Each update shall...

  11. The Updating of Geospatial Base Data

    NASA Astrophysics Data System (ADS)

    Alrajhi, Muhamad N.; Konecny, Gottfried

    2018-04-01

    Topopographic mapping issues concern the area coverage at different scales and their age. The age of the map is determined by the system of updating. The United Nations (UNGGIM) have attempted to track the global map coverage at various scale ranges, which has greatly improved in recent decades. However the poor state of updating of base maps is still a global problem. In Saudi Arabia large scale mapping is carried out for all urban, suburban and rural areas by aerial surveys. Updating is carried out by remapping every 5 to 10 years. Due to the rapid urban development this is not satisfactory, but faster update methods are forseen by use of high resolution satellite imagery and the improvement of object oriented geodatabase structures, which will permit to utilize various survey technologies to update the photogrammetry established geodatabases. The longterm goal is to create an geodata infrastructure, which exists in Great Britain or Germany.

  12. 76 FR 10246 - Updating Fire Safety Standards

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-02-24

    ... DEPARTMENT OF VETERANS AFFAIRS 38 CFR Parts 17 and 59 RIN 2900-AN57 Updating Fire Safety Standards... regulations and update the standards for VA approval of such facilities, including standards for fire safety... to ``RIN 2900-AN57--Updating Fire Safety [[Page 10247

  13. 40 CFR 68.190 - Updates.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 15 2011-07-01 2011-07-01 false Updates. 68.190 Section 68.190 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) CHEMICAL ACCIDENT PREVENTION PROVISIONS Risk Management Plan § 68.190 Updates. (a) The owner or operator shall...

  14. 40 CFR 68.190 - Updates.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 15 2010-07-01 2010-07-01 false Updates. 68.190 Section 68.190 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) CHEMICAL ACCIDENT PREVENTION PROVISIONS Risk Management Plan § 68.190 Updates. (a) The owner or operator shall...

  15. 10 CFR 72.248 - Safety analysis report updating.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... appropriate, the last update to the FSAR under this section. The update shall include the effects 1 of: 1... for a spent fuel storage cask design shall update periodically, as provided in paragraph (b) of this... the issued Certificate of Compliance (CoC). (b) Each update shall contain all the changes necessary to...

  16. 10 CFR 72.248 - Safety analysis report updating.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... appropriate, the last update to the FSAR under this section. The update shall include the effects 1 of: 1... for a spent fuel storage cask design shall update periodically, as provided in paragraph (b) of this... the issued Certificate of Compliance (CoC). (b) Each update shall contain all the changes necessary to...

  17. 10 CFR 72.248 - Safety analysis report updating.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... appropriate, the last update to the FSAR under this section. The update shall include the effects 1 of: 1... for a spent fuel storage cask design shall update periodically, as provided in paragraph (b) of this... the issued Certificate of Compliance (CoC). (b) Each update shall contain all the changes necessary to...

  18. 10 CFR 72.248 - Safety analysis report updating.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... appropriate, the last update to the FSAR under this section. The update shall include the effects 1 of: 1... for a spent fuel storage cask design shall update periodically, as provided in paragraph (b) of this... the issued Certificate of Compliance (CoC). (b) Each update shall contain all the changes necessary to...

  19. What Do We Know About NOD-Like Receptors in Plant Immunity?

    PubMed

    Zhang, Xiaoxiao; Dodds, Peter N; Bernoux, Maud

    2017-08-04

    The first plant disease resistance (R) genes were identified and cloned more than two decades ago. Since then, many more R genes have been identified and characterized in numerous plant pathosystems. Most of these encode members of the large family of intracellular NLRs (NOD-like receptors), which also includes animal immune receptors. New discoveries in this expanding field of research provide new elements for our understanding of plant NLR function. But what do we know about plant NLR function today? Genetic, structural, and functional analyses have uncovered a number of commonalities and differences in pathogen recognition strategies as well as how NLRs are regulated and activate defense signaling, but many unknowns remain. This review gives an update on the latest discoveries and breakthroughs in this field, with an emphasis on structural findings and some comparison to animal NLRs, which can provide additional insights and paradigms in plant NLR function.

  20. Email Updates About FASTSim | Transportation Research | NREL

    Science.gov Websites

    Email Updates About FASTSim Email Updates about FASTSim Subscribe Please provide the following information to subscribe for email updates about FASTSim, the Future Automotive Systems Technology Simulator . * indicates required Email Address: * Name (first and last): Organization/Affiliation: Subscribe

  1. Email Updates about ADOPT | Transportation Research | NREL

    Science.gov Websites

    Email Updates about ADOPT Email Updates about ADOPT Subscribe Please provide the following information to subscribe for email updates about ADOPT, the Automotive Deployment Options Projection Tool . * indicates required Email Address: * Name (first and last): Organization/Affiliation Subscribe

  2. Supersensitive Kappa Opioid Receptors Promotes Ethanol Withdrawal-Related Behaviors and Reduce Dopamine Signaling in the Nucleus Accumbens.

    PubMed

    Rose, Jamie H; Karkhanis, Anushree N; Chen, Rong; Gioia, Dominic; Lopez, Marcelo F; Becker, Howard C; McCool, Brian A; Jones, Sara R

    2016-05-01

    Chronic ethanol exposure reduces dopamine transmission in the nucleus accumbens, which may contribute to the negative affective symptoms associated with ethanol withdrawal. Kappa opioid receptors have been implicated in withdrawal-induced excessive drinking and anxiety-like behaviors and are known to inhibit dopamine release in the nucleus accumbens. The effects of chronic ethanol exposure on kappa opioid receptor-mediated changes in dopamine transmission at the level of the dopamine terminal and withdrawal-related behaviors were examined. Five weeks of chronic intermittent ethanol exposure in male C57BL/6 mice were used to examine the role of kappa opioid receptors in chronic ethanol-induced increases in ethanol intake and marble burying, a measure of anxiety/compulsive-like behavior. Drinking and marble burying were evaluated before and after chronic intermittent ethanol exposure, with and without kappa opioid receptor blockade by nor-binaltorphimine (10mg/kg i.p.). Functional alterations in kappa opioid receptors were assessed using fast scan cyclic voltammetry in brain slices containing the nucleus accumbens. Chronic intermittent ethanol-exposed mice showed increased ethanol drinking and marble burying compared with controls, which was attenuated with kappa opioid receptor blockade. Chronic intermittent ethanol-induced increases in behavior were replicated with kappa opioid receptor activation in naïve mice. Fast scan cyclic voltammetry revealed that chronic intermittent ethanol reduced accumbal dopamine release and increased uptake rates, promoting a hypodopaminergic state of this region. Kappa opioid receptor activation with U50,488H concentration-dependently decreased dopamine release in both groups; however, this effect was greater in chronic intermittent ethanol-treated mice, indicating kappa opioid receptor supersensitivity in this group. These data suggest that the chronic intermittent ethanol-induced increase in ethanol intake and anxiety

  3. Gallbladder radionuclide scan

    MedlinePlus

    ... Gallbladder scan; Biliary scan; Cholescintigraphy; HIDA; Hepatobiliary nuclear imaging scan ... test results. This test is combined with other imaging (such as CT or ultrasound). After the gallbladder ...

  4. 7. Mentor update and support: what do mentors need from an update?

    PubMed

    Phillips, Mari; Marshall, Joyce

    2015-04-01

    Mentorship is the 14th series of 'Midwifery basics' targeted at practising midwives. The aim of these articles is to provide information to raise awareness of the impact of the work of midwives on women's experience, and encourage midwives to seek further information through a series of activities relating to the topic. In this seventh article Mari Phillips and Joyce Marshall consider some of the key issues related to mentor update and support and consider what mentors need from their annual update.

  5. Renal scan

    MedlinePlus

    ... 11th ed. Philadelphia, PA: Elsevier; 2016:chap 141. Review Date 2/5/2017 Updated by: Jennifer Sobol, ... the Michigan Institute of Urology, West Bloomfield, MI. Review provided by VeriMed Healthcare Network. Also reviewed by ...

  6. Valence-Dependent Belief Updating: Computational Validation.

    PubMed

    Kuzmanovic, Bojana; Rigoux, Lionel

    2017-01-01

    People tend to update beliefs about their future outcomes in a valence-dependent way: they are likely to incorporate good news and to neglect bad news. However, belief formation is a complex process which depends not only on motivational factors such as the desire for favorable conclusions, but also on multiple cognitive variables such as prior beliefs, knowledge about personal vulnerabilities and resources, and the size of the probabilities and estimation errors. Thus, we applied computational modeling in order to test for valence-induced biases in updating while formally controlling for relevant cognitive factors. We compared biased and unbiased Bayesian models of belief updating, and specified alternative models based on reinforcement learning. The experiment consisted of 80 trials with 80 different adverse future life events. In each trial, participants estimated the base rate of one of these events and estimated their own risk of experiencing the event before and after being confronted with the actual base rate. Belief updates corresponded to the difference between the two self-risk estimates. Valence-dependent updating was assessed by comparing trials with good news (better-than-expected base rates) with trials with bad news (worse-than-expected base rates). After receiving bad relative to good news, participants' updates were smaller and deviated more strongly from rational Bayesian predictions, indicating a valence-induced bias. Model comparison revealed that the biased (i.e., optimistic) Bayesian model of belief updating better accounted for data than the unbiased (i.e., rational) Bayesian model, confirming that the valence of the new information influenced the amount of updating. Moreover, alternative computational modeling based on reinforcement learning demonstrated higher learning rates for good than for bad news, as well as a moderating role of personal knowledge. Finally, in this specific experimental context, the approach based on reinforcement

  7. Valence-Dependent Belief Updating: Computational Validation

    PubMed Central

    Kuzmanovic, Bojana; Rigoux, Lionel

    2017-01-01

    People tend to update beliefs about their future outcomes in a valence-dependent way: they are likely to incorporate good news and to neglect bad news. However, belief formation is a complex process which depends not only on motivational factors such as the desire for favorable conclusions, but also on multiple cognitive variables such as prior beliefs, knowledge about personal vulnerabilities and resources, and the size of the probabilities and estimation errors. Thus, we applied computational modeling in order to test for valence-induced biases in updating while formally controlling for relevant cognitive factors. We compared biased and unbiased Bayesian models of belief updating, and specified alternative models based on reinforcement learning. The experiment consisted of 80 trials with 80 different adverse future life events. In each trial, participants estimated the base rate of one of these events and estimated their own risk of experiencing the event before and after being confronted with the actual base rate. Belief updates corresponded to the difference between the two self-risk estimates. Valence-dependent updating was assessed by comparing trials with good news (better-than-expected base rates) with trials with bad news (worse-than-expected base rates). After receiving bad relative to good news, participants' updates were smaller and deviated more strongly from rational Bayesian predictions, indicating a valence-induced bias. Model comparison revealed that the biased (i.e., optimistic) Bayesian model of belief updating better accounted for data than the unbiased (i.e., rational) Bayesian model, confirming that the valence of the new information influenced the amount of updating. Moreover, alternative computational modeling based on reinforcement learning demonstrated higher learning rates for good than for bad news, as well as a moderating role of personal knowledge. Finally, in this specific experimental context, the approach based on reinforcement

  8. Herpes Simplex Encephalitis: an Update.

    PubMed

    Gnann, John W; Whitley, Richard J

    2017-03-01

    The goal of this review is to provide an update on current thinking regarding herpes simplex encephalitis (HSE), emphasizing new information about pathogenesis, diagnosis, and immune responses. Specific questions to be addressed are the following: (1) Is there a genetic predisposition to HSE? (2) What clinical approaches have the greatest impact on improving the long-term outcomes in patients with HSE? And (3) are there immune-mediated mechanisms that may account for relapsing HSE? Toll-like receptor 3 (TLR 3) plays an important role in innate immune responses, including generation of interferons. Multiple single-gene errors in TLR 3 interferon pathways have recently been described in children that result in increased susceptibility to HSE. Conversely, studies in both animal models and humans indicate that both cytolytic viral replication and immune-mediated responses (including cytotoxic T lymphocytes and immune mechanisms mediated by TLR 2) contribute to the pathology of HSV, suggesting possible new therapeutic approaches. In terms of treatment, data clearly indicate that a longer duration between onset of symptoms and initiation of effective antiviral therapy correlates directly with less favorable clinical outcome. Recurrent or relapsing HSE may occasionally occur, but recent observations indicate that many instances of "relapsing HSE", especially in children, are more often anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis triggered by the antecedent HSV infection. Innate immune responses are critical for defense against HSV; genetic defects in this system may predispose patients to HSE. During acute HSE, exuberant immune responses may contribute to the CNS pathology, suggesting that selective immunosuppressive therapy, coupled with potent antiviral drugs, may eventually play a role in the therapeutic management of HSV. While overall clinical outcomes of HSE remain suboptimal, the initiation of high-dose acyclovir therapy as early as possible in the

  9. Effects of Organotins on Crustaceans: Update and Perspectives

    PubMed Central

    Vogt, Éverton L.; Model, Jorge F. A.; Vinagre, Anapaula S.

    2018-01-01

    Organotins (OTs) are considered some of the most toxic chemicals introduced into aquatic environments by anthropogenic activities. They are widely used for agricultural and industrial purposes and as antifouling additives on boat hull’s paints. Even though the use of OTs was banned in 2008, elevated levels of OTs can still be detected in aquatic environments. OTs’ deleterious effects upon wildlife and experimental animals are well documented and include endocrine disruption, immunotoxicity, neurotoxicity, genotoxicity, and metabolic dysfunction. Crustaceans are key members of zooplankton and benthic communities and have vital roles in food chains, so the endocrine-disrupting effects of tributyltin (TBT) on crustaceans can affect other organisms. TBT can disrupt carbohydrate and lipid homeostasis of crustaceans by interacting with retinoid X receptor (RXR) and crustacean hyperglycemic hormone (CHH) signaling. Moreover, it can also interact with other nuclear receptors, disrupting methyl farnesoate and ecdysteroid signaling, thereby altering growth and sexual maturity, respectively. This compound also interferes in cytochrome P450 system disrupting steroid synthesis and reproduction. Crustaceans are also important fisheries worldwide, and its consumption can pose risks to human health. However, some questions remain unanswered. This mini review aims to update information about the effects of OTs on the metabolism, growth, and reproduction of crustaceans; to compare with known effects in mammals; and to point aspects that still needs to be addressed in future studies. Since both macrocrustaceans and microcrustaceans are good models to study the effects of sublethal TBT contamination, novel studies should be developed using multibiomarkers and omics technology. PMID:29535684

  10. 49 CFR 360.5 - Updating user fees.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... updating the cost components comprising the fee. Cost components shall be updated as follows: (1) Direct... determined by the cost study in Regulations Governing Fees For Service, 1 I.C.C. 2d 60 (1984), or subsequent... by total office costs for the office directly associated with user fee activity. Actual updating of...

  11. Protocol Independent Adaptive Route Update for VANET

    PubMed Central

    Rasheed, Asim; Qayyum, Amir

    2014-01-01

    High relative node velocity and high active node density have presented challenges to existing routing approaches within highly scaled ad hoc wireless networks, such as Vehicular Ad hoc Networks (VANET). Efficient routing requires finding optimum route with minimum delay, updating it on availability of a better one, and repairing it on link breakages. Current routing protocols are generally focused on finding and maintaining an efficient route, with very less emphasis on route update. Adaptive route update usually becomes impractical for dense networks due to large routing overheads. This paper presents an adaptive route update approach which can provide solution for any baseline routing protocol. The proposed adaptation eliminates the classification of reactive and proactive by categorizing them as logical conditions to find and update the route. PMID:24723807

  12. Updates Technologies of Media Change

    ERIC Educational Resources Information Center

    Comer, Joshua

    2015-01-01

    Whether as status notifications in news feeds or interactive prompts in online video services, updates punctuate the background routines of media by bringing a variety of changes to the attention of users. In this dissertation I argue that updates rationalize media change by making previously obscure actions of users and movements of technologies…

  13. Defining the system of care concept and philosophy: to update or not to update?

    PubMed

    Stroul, Beth A; Blau, Gary M

    2010-02-01

    This commentary considers the task of updating the system of care concept and philosophy within its historical context, reviewing the original intent of the definition and clarifying misconceptions about its meaning. The authors identify the aspects of the concept and philosophy that should be updated based on the latest thinking, experience, and data, such as incorporating applicability to a broader range of populations, increasing the emphasis on the core values, specifying desired outcomes, and adding accountability as a critical element. An updated definition and values and principles are proposed, and the importance of always presenting the definition along with the accompanying specification of the philosophy is emphasized in order to increase its utility in assisting the field to move from theory to practice.

  14. Abdominal CT scan

    MedlinePlus

    Computed tomography scan - abdomen; CT scan - abdomen; CT abdomen and pelvis ... An abdominal CT scan makes detailed pictures of the structures inside your belly very quickly. This test may be used to look ...

  15. Updated recommendations: an assessment of NICE clinical guidelines

    PubMed Central

    2014-01-01

    Background Updating is important to ensure clinical guideline (CG) recommendations remain valid. However, little research has been undertaken in this field. We assessed CGs produced by the National Institute for Health and Care Excellence (NICE) to identify and describe updated recommendations and to investigate potential factors associated with updating. Also, we evaluated the reporting and presentation of recommendation changes. Methods We performed a descriptive analysis of original and updated CGs and recommendations, and an assessment of presentation formats and methods for recording information. We conducted a case-control study, defining cases as original recommendations that were updated (‘new-replaced’ recommendations), and controls as original recommendations that were considered to remain valid (‘not changed’ recommendations). We performed a comparison of main characteristics between cases and controls, and we planned a multiple regression analysis to identify potential predictive factors for updating. Results We included nine updated CGs (1,306 recommendations) and their corresponding original versions (1,106 recommendations). Updated CGs included 812 (62%) recommendations ‘not reviewed’, 368 (28.1%) ‘new’ recommendations, 104 (7.9%) ‘amended’ recommendations, and 25 (1.9%) recommendations reviewed but unchanged. The presentation formats used to indicate the changes in recommendations varied widely across CGs. Changes in ‘amended’, ‘deleted’, and ‘new-replaced’ recommendations (n = 296) were reported infrequently, mostly in appendices. These changes were recorded in 167 (56.4%) recommendations; and were explained in 81 (27.4%) recommendations. We retrieved a total of 7.1% (n = 78) case recommendations (‘new-replaced’) and 2.4% (n = 27) control recommendations (‘not changed’) in original CGs. The updates were mainly from ‘Fertility CG’, about ‘gynaecology, pregnancy and birth’ topic, and

  16. NASA Update

    NASA Image and Video Library

    2010-04-08

    "NASA Update" program with NASA Administrator Charles Bolden, NASA Deputy Administrator Lori Garver and NASA Acting Asistant Administrator for Public Affairs Bob Jacobs as moderator, NASA Headquarters, Thursday, April 8, 2010 in Washington. Photo Credit: (NASA/Bill Ingalls)

  17. Effects of scanning and eliminating paper-based medical records on hospital physicians' clinical work practice.

    PubMed

    Laerum, Hallvard; Karlsen, Tom H; Faxvaag, Arild

    2003-01-01

    It is not automatically given that the paper-based medical record can be eliminated after the introduction of an electronic medical record (EMR) in a hospital. Many keep and update the paper-based counterpart, and this limits the use of the EMR system. The authors have evaluated the physicians' clinical work practices and attitudes toward a system in a hospital that has eliminated the paper-based counterpart using scanning technology. Combined open-ended interviews (8 physicians) and cross-sectional survey (70 physicians) were conducted and compared with reference data from a previous national survey (69 physicians from six hospitals). The hospitals in the reference group were using the same EMR system without the scanning module. The questionnaire (English translation available as an online data supplement at ) covered frequency of use of the EMR system for 19 defined tasks, ease of performing them, and user satisfaction. The interviews were open-ended. The physicians routinely used the system for nine of 11 tasks regarding retrieval of patient data, which the majority of the physicians found more easily performed than before. However, 22% to 25% of the physicians found retrieval of patient data more difficult, particularly among internists (33%). Overall, the physicians were equally satisfied with the part of the system handling the regular electronic data as that of the physicians in the reference group. They were, however, much less satisfied with the use of scanned document images than that of regular electronic data, using the former less frequently than the latter. Scanning and elimination of the paper-based medical record is feasible, but the scanned document images should be considered an intermediate stage toward fully electronic medical records. To our knowledge, this is the first assessment from a hospital in the process of completing such a scanning project.

  18. A comparison of caveolae and caveolin-1 to folate receptor α in retina and retinal pigment epithelium

    PubMed Central

    Bridges, Christy C.; El-Sherbeny, Amira; Roon, Penny; Ola, M. Shamsul; Kekuda, Ramesh; Ganapathy, Vadivel; Cameron, Richard S.; Cameron, Patricia L.

    2015-01-01

    Summary Caveolae are flask-shaped membrane invaginations present in most mammalian cells. They are distinguished by the presence of a striated coat composed of the protein, caveolin. Caveolae have been implicated in numerous cellular processes, including potocytosis in which caveolae are hypothesized to co-localize with folate receptor α and participate in folate uptake. Our laboratory has recently localized folate receptor α to the basolateral surface of the retinal pigment epithelium (RPE). It is present also in many other cells of the retina. In the present study, we asked whether caveolae were present in the RPE, and if so, whether their pattern of distribution was similar to folate receptor α. We also examined the distribution pattern of caveolin-1, which can be a marker of caveolae. Extensive electron microscopical analysis revealed caveolae associated with endothelial cells. However, none were detected in intact or cultured RPE. Laser scanning confocal microscopical analysis of intact RPE localized caveolin-1 to the apical and basal surfaces, a distribution unlike folate receptor α. Western analysis confirmed the presence of caveolin-1 in cultured RPE cells and laser scanning confocal microscopy localized the protein to the basal plasma membrane of the RPE, a distribution like that of folate receptor α. This distribution was confirmed by electron microscopic immunolocalization. The lack of caveolae in the RPE suggests that these structures may not be essential for folate internalization in the RPE. PMID:11508338

  19. Email Updates

    MedlinePlus

    ... MedlinePlus GO GO About MedlinePlus Site Map FAQs Customer Support Health Topics Drugs & Supplements Videos & Tools Español ... spam" or "junk." About MedlinePlus Site Map FAQs Customer Support Get email updates Subscribe to RSS Follow ...

  20. Breast Cancer and Estrogen-Alone Update

    MedlinePlus

    ... Current Issue Past Issues Research News From NIH Breast Cancer and Estrogen-Alone Update Past Issues / Summer 2006 ... hormone therapy does not increase the risk of breast cancer in postmenopausal women, according to an updated analysis ...

  1. Working Memory Updating as a Predictor of Academic Attainment

    ERIC Educational Resources Information Center

    Lechuga, M. Teresa; Pelegrina, Santiago; Pelaez, Jose L.; Martin-Puga, M. Eva; Justicia, M. Jose

    2016-01-01

    There is growing evidence supporting the importance of executive functions, and specifically working memory updating (WMU), for children's academic achievement. This study aimed to assess the specific contribution of updating to the prediction of academic performance. Two updating tasks, which included different updating components, were…

  2. Cerebral glucose metabolism and D2/D3 receptor availability in young adults with cannabis dependence measured with positron emission tomography.

    PubMed

    Sevy, Serge; Smith, Gwenn S; Ma, Yilong; Dhawan, Vijay; Chaly, Thomas; Kingsley, Peter B; Kumra, Sanjiv; Abdelmessih, Sherif; Eidelberg, David

    2008-05-01

    Cannabis users have been reported to have decreased regional cerebral glucose metabolism after short periods of abstinence. The purpose of this study was to measure striatal dopamine receptor (D2/D3) availability and cerebral glucose metabolism with positron emission tomography (PET) in young adults who had a prolonged exposure to cannabis and who had been abstinent for a period of at least 12 weeks. Six 18-21-year-old male subjects with cannabis dependence in early full remission and six age- and sex-matched healthy subjects underwent PET scans for D2/D3 receptor availability measured with [C11]-raclopride and glucose metabolism measured with [18F]-FDG. All subjects were sober for at least 12 weeks before PET scan procedures. PET data were analyzed with statistical parametric mapping software (SPM99; uncorrected p < 0.001, corrected p < 0.05 at the cluster level). Toxicology screening was performed prior to the PET scan to confirm the lack of drugs of abuse. Striatal D2/D3 receptor availability did not differ significantly between groups. Compared to controls, subjects with cannabis dependence had lower normalized glucose metabolism in the right orbitofrontal cortex, putamen bilaterally, and precuneus. There were no significant correlations between striatal D2/D3 receptor availability and normalized glucose metabolism in any region of the frontal cortex or striatum. These findings may reflect both cannabis exposure and adaptive changes that occur after a prolonged period of abstinence. Subsequent studies should address whether metabolic and dopamine receptor effects are associated with either active use or longer-term withdrawal in these relatively young subjects.

  3. Real-Time Noise Removal for Line-Scanning Hyperspectral Devices Using a Minimum Noise Fraction-Based Approach

    PubMed Central

    Bjorgan, Asgeir; Randeberg, Lise Lyngsnes

    2015-01-01

    Processing line-by-line and in real-time can be convenient for some applications of line-scanning hyperspectral imaging technology. Some types of processing, like inverse modeling and spectral analysis, can be sensitive to noise. The MNF (minimum noise fraction) transform provides suitable denoising performance, but requires full image availability for the estimation of image and noise statistics. In this work, a modified algorithm is proposed. Incrementally-updated statistics enables the algorithm to denoise the image line-by-line. The denoising performance has been compared to conventional MNF and found to be equal. With a satisfying denoising performance and real-time implementation, the developed algorithm can denoise line-scanned hyperspectral images in real-time. The elimination of waiting time before denoised data are available is an important step towards real-time visualization of processed hyperspectral data. The source code can be found at http://www.github.com/ntnu-bioopt/mnf. This includes an implementation of conventional MNF denoising. PMID:25654717

  4. Program Updates - San Antonio River Basin

    EPA Pesticide Factsheets

    This page will house updates for this urban waters partnership location. As projects progress, status updates can be posted here to reflect the ongoing work by partners in San Antonio working on the San Antonio River Basin.

  5. CT scan

    MedlinePlus

    ... this page: //medlineplus.gov/ency/article/003330.htm CT scan To use the sharing features on this page, please enable JavaScript. A computed tomography (CT) scan is an imaging method that uses x- ...

  6. Precursor and Neutral Loss Scans in an RF Scanning Linear Quadrupole Ion Trap

    NASA Astrophysics Data System (ADS)

    Snyder, Dalton T.; Szalwinski, Lucas J.; Schrader, Robert L.; Pirro, Valentina; Hilger, Ryan; Cooks, R. Graham

    2018-03-01

    Methodology for performing precursor and neutral loss scans in an RF scanning linear quadrupole ion trap is described and compared to the unconventional ac frequency scan technique. In the RF scanning variant, precursor ions are mass selectively excited by a fixed frequency resonance excitation signal at low Mathieu q while the RF amplitude is ramped linearly to pass ions through the point of excitation such that the excited ion's m/z varies linearly with time. Ironically, a nonlinear ac frequency scan is still required for ejection of the product ions since their frequencies vary nonlinearly with the linearly varying RF amplitude. In the case of the precursor scan, the ejection frequency must be scanned so that it is fixed on a product ion m/z throughout the RF scan, whereas in the neutral loss scan, it must be scanned to maintain a constant mass offset from the excited precursor ions. Both simultaneous and sequential permutation scans are possible; only the former are demonstrated here. The scans described are performed on a variety of samples using different ionization sources: protonated amphetamine ions generated by nanoelectrospray ionization (nESI), explosives ionized by low-temperature plasma (LTP), and chemical warfare agent simulants sampled from a surface and analyzed with swab touch spray (TS). We lastly conclude that the ac frequency scan variant of these MS/MS scans is preferred due to electronic simplicity. In an accompanying manuscript, we thus describe the implementation of orthogonal double resonance precursor and neutral loss scans on the Mini 12 using constant RF voltage. [Figure not available: see fulltext.

  7. The neural systems for perceptual updating.

    PubMed

    Stöttinger, Elisabeth; Aichhorn, Markus; Anderson, Britt; Danckert, James

    2018-04-01

    In a constantly changing environment we must adapt to both abrupt and gradual changes to incoming information. Previously, we demonstrated that a distributed network (including the anterior insula and anterior cingulate cortex) was active when participants updated their initial representations (e.g., it's a cat) in a gradually morphing picture task (e.g., now it's a rabbit; Stöttinger et al., 2015). To shed light on whether these activations reflect the proactive decisions to update or perceptual uncertainty, we introduced two additional conditions. By presenting picture morphs twice we controlled for uncertainty in perceptual decision making. Inducing an abrupt shift in a third condition allowed us to differentiate between a proactive decision in uncertainty-driven updating and a reactive decision in surprise-based updating. We replicated our earlier result, showing the robustness of the effect. In addition, we found activation in the anterior insula (bilaterally) and the mid frontal area/ACC in all three conditions, indicative of the importance of these areas in updating of all kinds. When participants were naïve as to the identity of the second object, we found higher activations in the mid-cingulate cortex and cuneus - areas typically associated with task difficulty, in addition to higher activations in the right TPJ most likely reflecting the shift to a new perspective. Activations associated with the proactive decision to update to a new interpretation were found in a network including the dorsal ACC known to be involved in exploration and the endogenous decision to switch to a new interpretation. These findings suggest a general network commonly engaged in all types of perceptual decision making supported by additional networks associated with perceptual uncertainty or updating provoked by either proactive or reactive decision making. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

  8. Indoor Spatial Updating With Impaired Vision

    PubMed Central

    Legge, Gordon E.; Granquist, Christina; Baek, Yihwa; Gage, Rachel

    2016-01-01

    Purpose Spatial updating is the ability to keep track of position and orientation while moving through an environment. We asked how normally sighted and visually impaired subjects compare in spatial updating and in estimating room dimensions. Methods Groups of 32 normally sighted, 16 low-vision, and 16 blind subjects estimated the dimensions of six rectangular rooms. Updating was assessed by guiding the subjects along three-segment paths in the rooms. At the end of each path, they estimated the distance and direction to the starting location, and to a designated target. Spatial updating was tested in five conditions ranging from free viewing to full auditory and visual deprivation. Results The normally sighted and low-vision groups did not differ in their accuracy for judging room dimensions. Correlations between estimated size and physical size were high. Accuracy of low-vision performance was not correlated with acuity, contrast sensitivity, or field status. Accuracy was lower for the blind subjects. The three groups were very similar in spatial-updating performance, and exhibited only weak dependence on the nature of the viewing conditions. Conclusions People with a wide range of low-vision conditions are able to judge room dimensions as accurately as people with normal vision. Blind subjects have difficulty in judging the dimensions of quiet rooms, but some information is available from echolocation. Vision status has little impact on performance in simple spatial updating; proprioceptive and vestibular cues are sufficient. PMID:27978556

  9. Indoor Spatial Updating With Impaired Vision.

    PubMed

    Legge, Gordon E; Granquist, Christina; Baek, Yihwa; Gage, Rachel

    2016-12-01

    Spatial updating is the ability to keep track of position and orientation while moving through an environment. We asked how normally sighted and visually impaired subjects compare in spatial updating and in estimating room dimensions. Groups of 32 normally sighted, 16 low-vision, and 16 blind subjects estimated the dimensions of six rectangular rooms. Updating was assessed by guiding the subjects along three-segment paths in the rooms. At the end of each path, they estimated the distance and direction to the starting location, and to a designated target. Spatial updating was tested in five conditions ranging from free viewing to full auditory and visual deprivation. The normally sighted and low-vision groups did not differ in their accuracy for judging room dimensions. Correlations between estimated size and physical size were high. Accuracy of low-vision performance was not correlated with acuity, contrast sensitivity, or field status. Accuracy was lower for the blind subjects. The three groups were very similar in spatial-updating performance, and exhibited only weak dependence on the nature of the viewing conditions. People with a wide range of low-vision conditions are able to judge room dimensions as accurately as people with normal vision. Blind subjects have difficulty in judging the dimensions of quiet rooms, but some information is available from echolocation. Vision status has little impact on performance in simple spatial updating; proprioceptive and vestibular cues are sufficient.

  10. Precision controlled atomic resolution scanning transmission electron microscopy using spiral scan pathways

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Sang, Xiahan; Lupini, Andrew R.; Ding, Jilai

    Atomic-resolution imaging in an aberration-corrected scanning transmission electron microscope (STEM) can enable direct correlation between atomic structure and materials functionality. The fast and precise control of the STEM probe is, however, challenging because the true beam location deviates from the assigned location depending on the properties of the deflectors. To reduce these deviations, i.e. image distortions, we use spiral scanning paths, allowing precise control of a sub-Å sized electron probe within an aberration-corrected STEM. Although spiral scanning avoids the sudden changes in the beam location (fly-back distortion) present in conventional raster scans, it is not distortion-free. “Archimedean” spirals, with amore » constant angular frequency within each scan, are used to determine the characteristic response at different frequencies. We then show that such characteristic functions can be used to correct image distortions present in more complicated constant linear velocity spirals, where the frequency varies within each scan. Through the combined application of constant linear velocity scanning and beam path corrections, spiral scan images are shown to exhibit less scan distortion than conventional raster scan images. The methodology presented here will be useful for in situ STEM imaging at higher temporal resolution and for imaging beam sensitive materials.« less

  11. Precision controlled atomic resolution scanning transmission electron microscopy using spiral scan pathways

    NASA Astrophysics Data System (ADS)

    Sang, Xiahan; Lupini, Andrew R.; Ding, Jilai; Kalinin, Sergei V.; Jesse, Stephen; Unocic, Raymond R.

    2017-03-01

    Atomic-resolution imaging in an aberration-corrected scanning transmission electron microscope (STEM) can enable direct correlation between atomic structure and materials functionality. The fast and precise control of the STEM probe is, however, challenging because the true beam location deviates from the assigned location depending on the properties of the deflectors. To reduce these deviations, i.e. image distortions, we use spiral scanning paths, allowing precise control of a sub-Å sized electron probe within an aberration-corrected STEM. Although spiral scanning avoids the sudden changes in the beam location (fly-back distortion) present in conventional raster scans, it is not distortion-free. “Archimedean” spirals, with a constant angular frequency within each scan, are used to determine the characteristic response at different frequencies. We then show that such characteristic functions can be used to correct image distortions present in more complicated constant linear velocity spirals, where the frequency varies within each scan. Through the combined application of constant linear velocity scanning and beam path corrections, spiral scan images are shown to exhibit less scan distortion than conventional raster scan images. The methodology presented here will be useful for in situ STEM imaging at higher temporal resolution and for imaging beam sensitive materials.

  12. Precision controlled atomic resolution scanning transmission electron microscopy using spiral scan pathways.

    PubMed

    Sang, Xiahan; Lupini, Andrew R; Ding, Jilai; Kalinin, Sergei V; Jesse, Stephen; Unocic, Raymond R

    2017-03-08

    Atomic-resolution imaging in an aberration-corrected scanning transmission electron microscope (STEM) can enable direct correlation between atomic structure and materials functionality. The fast and precise control of the STEM probe is, however, challenging because the true beam location deviates from the assigned location depending on the properties of the deflectors. To reduce these deviations, i.e. image distortions, we use spiral scanning paths, allowing precise control of a sub-Å sized electron probe within an aberration-corrected STEM. Although spiral scanning avoids the sudden changes in the beam location (fly-back distortion) present in conventional raster scans, it is not distortion-free. "Archimedean" spirals, with a constant angular frequency within each scan, are used to determine the characteristic response at different frequencies. We then show that such characteristic functions can be used to correct image distortions present in more complicated constant linear velocity spirals, where the frequency varies within each scan. Through the combined application of constant linear velocity scanning and beam path corrections, spiral scan images are shown to exhibit less scan distortion than conventional raster scan images. The methodology presented here will be useful for in situ STEM imaging at higher temporal resolution and for imaging beam sensitive materials.

  13. Precision controlled atomic resolution scanning transmission electron microscopy using spiral scan pathways

    DOE PAGES

    Sang, Xiahan; Lupini, Andrew R.; Ding, Jilai; ...

    2017-03-08

    Atomic-resolution imaging in an aberration-corrected scanning transmission electron microscope (STEM) can enable direct correlation between atomic structure and materials functionality. The fast and precise control of the STEM probe is, however, challenging because the true beam location deviates from the assigned location depending on the properties of the deflectors. To reduce these deviations, i.e. image distortions, we use spiral scanning paths, allowing precise control of a sub-Å sized electron probe within an aberration-corrected STEM. Although spiral scanning avoids the sudden changes in the beam location (fly-back distortion) present in conventional raster scans, it is not distortion-free. “Archimedean” spirals, with amore » constant angular frequency within each scan, are used to determine the characteristic response at different frequencies. We then show that such characteristic functions can be used to correct image distortions present in more complicated constant linear velocity spirals, where the frequency varies within each scan. Through the combined application of constant linear velocity scanning and beam path corrections, spiral scan images are shown to exhibit less scan distortion than conventional raster scan images. The methodology presented here will be useful for in situ STEM imaging at higher temporal resolution and for imaging beam sensitive materials.« less

  14. Implication of Genes for the N-Methyl-D-Aspartate (NMDA) Receptor in Substance Addictions.

    PubMed

    Chen, Jiali; Ma, Yunlong; Fan, Rongli; Yang, Zhongli; Li, Ming D

    2018-02-10

    Drug dependence is a chronic brain disease with harmful consequences for both individual users and society. Glutamate is a primary excitatory neurotransmitter in the brain, and both in vivo and in vitro experiments have implicated N-methyl-D-aspartate (NMDA) receptor, a glutamate receptor, as an element in various types of addiction. Recent findings from genetics-based approaches such as genome-wide linkage, candidate gene association, genome-wide association (GWA), and next-generation sequencing have demonstrated the significant association of NMDA receptor subunit genes such as GluN3A, GluN2B, and GluN2A with various addiction-related phenotypes. Of these genes, GluN3A has been the most studied, and it has been revealed to play crucial roles in the etiology of addictions. In this communication, we provide an updated view of the genetic effects of NMDA receptor subunit genes and their functions in the etiology of addictions based on the findings from investigation of both common and rare variants as well as SNP-SNP interactions. To better understand the molecular mechanisms underlying addiction-related behaviors and to promote the development of specific medicines for the prevention and treatment of addictions, current efforts aim not only to identify more causal variants in NMDA receptor subunits by using large independent samples but also to reveal the molecular functions of these variants in addictions.

  15. Neutrophils Express Distinct RNA Receptors in a Non-canonical Way*

    PubMed Central

    Berger, Michael; Hsieh, Chin-Yuan; Bakele, Martina; Marcos, Veronica; Rieber, Nikolaus; Kormann, Michael; Mays, Lauren; Hofer, Laura; Neth, Olaf; Vitkov, Ljubomir; Krautgartner, Wolf Dietrich; von Schweinitz, Dietrich; Kappler, Roland; Hector, Andreas; Weber, Alexander; Hartl, Dominik

    2012-01-01

    RNAs are capable of modulating immune responses by binding to specific receptors. Neutrophils represent the major fraction of circulating immune cells, but receptors and mechanisms by which neutrophils sense RNA are poorly defined. Here, we analyzed the mRNA and protein expression patterns and the subcellular localization of the RNA receptors RIG-I, MDA-5, TLR3, TLR7, and TLR8 in primary neutrophils and immortalized neutrophil-like differentiated HL-60 cells. Our results demonstrate that both neutrophils and differentiated HL-60 cells express RIG-I, MDA-5, and TLR8 at the mRNA and protein levels, whereas TLR3 and TLR7 are not expressed at the protein level. Subcellular fractionation, flow cytometry, confocal laser scanning microscopy, and immuno-transmission electron microscopy provided evidence that, besides the cytoplasm, RIG-I and MDA-5 are stored in secretory vesicles of neutrophils and showed that RIG-I and its ligand, 3p-RNA, co-localize at the cell surface without triggering neutrophil activation. In summary, this study demonstrates that neutrophils express a distinct pattern of RNA recognition receptors in a non-canonical way, which could have essential implications for future RNA-based therapeutics. PMID:22532562

  16. Recent Updates on Peroxisome Proliferator-Activated Receptor δ Agonists for the Treatment of Metabolic Syndrome.

    PubMed

    Grewal, Ajmer S; Beniwal, Meenu; Pandita, Deepti; Sekhon, Bhupinder S; Lather, Viney

    2016-01-01

    Metabolic syndrome is a disorder described by reduced insulin sensitivity, overweight, hyperlipidaemia, high blood pressure and myocardial disorders, mainly due to high fat diet and lack of physical activity. The peroxisome proliferator activated receptors (PPARs) are type II nuclear hormone receptors that regulate a number of processes in living systems, such as metabolism of carbohydrates and fatty acids, growth and differentiation of cell, and inflammatory reactions. Alpha, gamma and delta are the three distinct isoforms of PPAR. The stimulation of PPARδ alters body's energy fuel preference from glucose to fat. The PPARδ isoform is expressed ubiquitously in all tissues, especially in those tissues which involved in metabolism of lipids like adipose tissue, liver, kidney, and muscle. Currently, PPARδ is an emerging therapeutic target for the pharmacological therapy of disorders associated with metabolic syndrome. Several PPARδ selective agonists had been reported in last ten years, many of them had been advanced into the late phase of clinical trials such as Endurobol (GW501516). However, no PPARδ agonists are yet approved for human use. The present work had been planned to cover wide variety of PPARδ agonists reported till now along with their potential role to tackle various metabolic disorders. The present review has been planned to focus mainly the most popular PPARδ agonists.

  17. CT Scans

    MedlinePlus

    ... cross-sectional pictures of your body. Doctors use CT scans to look for Broken bones Cancers Blood clots Signs of heart disease Internal bleeding During a CT scan, you lie still on a table. The table ...

  18. Bone scan

    MedlinePlus

    ... scan is an imaging test used to diagnose bone diseases and find out how severe they are. How ... a 3-phase bone scan. To evaluate metastatic bone disease, images are taken only after the 3- to ...

  19. Low-cost compact MEMS scanning ladar system for robotic applications

    NASA Astrophysics Data System (ADS)

    Moss, Robert; Yuan, Ping; Bai, Xiaogang; Quesada, Emilio; Sudharsanan, Rengarajan; Stann, Barry L.; Dammann, John F.; Giza, Mark M.; Lawler, William B.

    2012-06-01

    Future robots and autonomous vehicles require compact low-cost Laser Detection and Ranging (LADAR) systems for autonomous navigation. Army Research Laboratory (ARL) had recently demonstrated a brass-board short-range eye-safe MEMS scanning LADAR system for robotic applications. Boeing Spectrolab is doing a tech-transfer (CRADA) of this system and has built a compact MEMS scanning LADAR system with additional improvements in receiver sensitivity, laser system, and data processing system. Improved system sensitivity, low-cost, miniaturization, and low power consumption are the main goals for the commercialization of this LADAR system. The receiver sensitivity has been improved by 2x using large-area InGaAs PIN detectors with low-noise amplifiers. The FPGA code has been updated to extend the range to 50 meters and detect up to 3 targets per pixel. Range accuracy has been improved through the implementation of an optical T-Zero input line. A compact commercially available erbium fiber laser operating at 1550 nm wavelength is used as a transmitter, thus reducing the size of the LADAR system considerably from the ARL brassboard system. The computer interface has been consolidated to allow image data and configuration data (configuration settings and system status) to pass through a single Ethernet port. In this presentation we will discuss the system architecture and future improvements to receiver sensitivity using avalanche photodiodes.

  20. Particle Filtering Methods for Incorporating Intelligence Updates

    DTIC Science & Technology

    2017-03-01

    methodology for incorporating intelligence updates into a stochastic model for target tracking. Due to the non -parametric assumptions of the PF...samples are taken with replacement from the remaining non -zero weighted particles at each iteration. With this methodology , a zero-weighted particle is...incorporation of information updates. A common method for incorporating information updates is Kalman filtering. However, given the probable nonlinear and non

  1. Technical Note: Comparison of first- and second-generation photon-counting slit-scanning tomosynthesis systems.

    PubMed

    Berggren, Karl; Cederström, Björn; Lundqvist, Mats; Fredenberg, Erik

    2018-02-01

    Digital breast tomosynthesis (DBT) is an emerging tool for breast-cancer screening and diagnostics. The purpose of this study is to present a second-generation photon-counting slit-scanning DBT system and compare it to the first-generation system in terms of geometry and image quality. The study presents the first image-quality measurements on the second-generation system. The geometry of the new system is based on a combined rotational and linear motion, in contrast to a purely rotational scan motion in the first generation. In addition, the calibration routines have been updated. Image quality was measured in the center of the image field in terms of in-slice modulation transfer function (MTF), artifact spread function (ASF), and in-slice detective quantum efficiency (DQE). Images were acquired using a W/Al 29 kVp spectrum at 13 mAs with 2 mm Al additional filtration and reconstructed using simple back-projection. The in-slice 50% MTF was improved in the chest-mammilla direction, going from 3.2 to 3.5 lp/mm, and the zero-frequency DQE increased from 0.71 to 0.77. The MTF and ASF were otherwise found to be on par for the two systems. The new system has reduced in-slice variation of the tomographic angle. The new geometry is less curved, which reduces in-slice tomographic-angle variation, and increases the maximum compression height, making the system accessible for a larger population. The improvements in MTF and DQE were attributed to the updated calibration procedures. We conclude that the second-generation system maintains the key features of the photon-counting system while maintaining or improving image quality and improving the maximum compression height. © 2017 American Association of Physicists in Medicine.

  2. Somatostatin receptor imaging in non-(131)I-avid metastatic differentiated thyroid carcinoma for determining the feasibility of peptide receptor radionuclide therapy with (177)Lu-DOTATATE: low fraction of patients suitable for peptide receptor radionuclide therapy and evidence of chromogranin A level-positive neuroendocrine differentiation.

    PubMed

    Jois, Bhargavi; Asopa, Ramesh; Basu, Sandip

    2014-06-01

    The aim of the study was to evaluate somatostatin receptor expression in non-I-concentrating metastatic differentiated thyroid carcinoma by Ga-DOTATATE PET-CT/Tc-HYNIC-TOC scintigraphy and to determine the feasibility of Lu-DOTATATE (therapeutic analog) therapy in cases with positive Ga-DOTATATE PET-CT/Tc-HYNIC-TOC scintigraphy. In this research study, 19 patients diagnosed with differentiated thyroid carcinoma with non-iodine-concentrating metastasis with elevated serum thyroglobulin levels, attending thyroid outpatient department for follow-up, underwent Ga-DOTATATE PET-CT/Tc-HYNIC-TOC scan for the evaluation of positivity of somatostatin receptor (SSTR). Based on the visual grading, SSTR-positive lesions were graded into 4 categories (grades I-IV) in comparison with the hepatic uptake on the scan. Patients with grades III and IV uptake in lesions (equal to or more than hepatic uptake on scan) were scheduled for Lu-DOTATATE administration. Posttherapy Lu-DOTATATE scan was undertaken during discharge from the isolation ward. Of the 19 patients studied, 12 patients (63%) showed SSTR-positive lesion expression demonstrating uptake ranging from grade I-IV, and 7 patients (37%) did not demonstrate any tracer uptake. On a lesion-specific analysis, of the total 57 metastatic lesions, 4 lesions (7%) demonstrated grade I tracer uptake, 18 lesions (31%) grade II (less than liver), 2 lesions (3.5%) grade III (equal to liver uptake), and 1 lesion showed grade IV uptake (more than liver). Interestingly, an elevated serum chromogranin A level was documented in 3 of the patients with grades III and IV tumor uptake. A comparison of Ga-DOTATATE PET-CT and Tc-HYNIC-TOC in 4 patients who underwent both the scans demonstrated no significant differences in the tracer concentration in the metastatic lesions in any of the patients on visual grading. Based on the criterion of high tracer uptake and the patient consent, finally 2 of 3 patients were treated with Lu-DOTATATE. On follow

  3. Clinical anthropometrics and body composition from 3D whole-body surface scans

    PubMed Central

    Ng, BK; Hinton, BJ; Fan, B; Kanaya, AM; Shepherd, JA

    2017-01-01

    BACKGROUND/OBJECTIVES Obesity is a significant worldwide epidemic that necessitates accessible tools for robust body composition analysis. We investigated whether widely available 3D body surface scanners can provide clinically relevant direct anthropometrics (circumferences, areas and volumes) and body composition estimates (regional fat/lean masses). SUBJECTS/METHODS Thirty-nine healthy adults stratified by age, sex and body mass index (BMI) underwent whole-body 3D scans, dual energy X-ray absorptiometry (DXA), air displacement plethysmography and tape measurements. Linear regressions were performed to assess agreement between 3D measurements and criterion methods. Linear models were derived to predict DXA body composition from 3D scan measurements. Thirty-seven external fitness center users underwent 3D scans and bioelectrical impedance analysis for model validation. RESULTS 3D body scan measurements correlated strongly to criterion methods: waist circumference R2 = 0.95, hip circumference R2 = 0.92, surface area R2 = 0.97 and volume R2 = 0.99. However, systematic differences were observed for each measure due to discrepancies in landmark positioning. Predictive body composition equations showed strong agreement for whole body (fat mass R2 = 0.95, root mean square error (RMSE) = 2.4 kg; fat-free mass R2 = 0.96, RMSE = 2.2 kg) and arms, legs and trunk (R2 = 0.79–0.94, RMSE = 0.5–1.7 kg). Visceral fat prediction showed moderate agreement (R2 = 0.75, RMSE = 0.11 kg). CONCLUSIONS 3D surface scanners offer precise and stable automated measurements of body shape and composition. Software updates may be needed to resolve measurement biases resulting from landmark positioning discrepancies. Further studies are justified to elucidate relationships between body shape, composition and metabolic health across sex, age, BMI and ethnicity groups, as well as in those with metabolic disorders. PMID:27329614

  4. Clinical anthropometrics and body composition from 3D whole-body surface scans.

    PubMed

    Ng, B K; Hinton, B J; Fan, B; Kanaya, A M; Shepherd, J A

    2016-11-01

    Obesity is a significant worldwide epidemic that necessitates accessible tools for robust body composition analysis. We investigated whether widely available 3D body surface scanners can provide clinically relevant direct anthropometrics (circumferences, areas and volumes) and body composition estimates (regional fat/lean masses). Thirty-nine healthy adults stratified by age, sex and body mass index (BMI) underwent whole-body 3D scans, dual energy X-ray absorptiometry (DXA), air displacement plethysmography and tape measurements. Linear regressions were performed to assess agreement between 3D measurements and criterion methods. Linear models were derived to predict DXA body composition from 3D scan measurements. Thirty-seven external fitness center users underwent 3D scans and bioelectrical impedance analysis for model validation. 3D body scan measurements correlated strongly to criterion methods: waist circumference R 2 =0.95, hip circumference R 2 =0.92, surface area R 2 =0.97 and volume R 2 =0.99. However, systematic differences were observed for each measure due to discrepancies in landmark positioning. Predictive body composition equations showed strong agreement for whole body (fat mass R 2 =0.95, root mean square error (RMSE)=2.4 kg; fat-free mass R 2 =0.96, RMSE=2.2 kg) and arms, legs and trunk (R 2 =0.79-0.94, RMSE=0.5-1.7 kg). Visceral fat prediction showed moderate agreement (R 2 =0.75, RMSE=0.11 kg). 3D surface scanners offer precise and stable automated measurements of body shape and composition. Software updates may be needed to resolve measurement biases resulting from landmark positioning discrepancies. Further studies are justified to elucidate relationships between body shape, composition and metabolic health across sex, age, BMI and ethnicity groups, as well as in those with metabolic disorders.

  5. Scanning sequences after Gibbs sampling to find multiple occurrences of functional elements

    PubMed Central

    Tharakaraman, Kannan; Mariño-Ramírez, Leonardo; Sheetlin, Sergey L; Landsman, David; Spouge, John L

    2006-01-01

    Background Many DNA regulatory elements occur as multiple instances within a target promoter. Gibbs sampling programs for finding DNA regulatory elements de novo can be prohibitively slow in locating all instances of such an element in a sequence set. Results We describe an improvement to the A-GLAM computer program, which predicts regulatory elements within DNA sequences with Gibbs sampling. The improvement adds an optional "scanning step" after Gibbs sampling. Gibbs sampling produces a position specific scoring matrix (PSSM). The new scanning step resembles an iterative PSI-BLAST search based on the PSSM. First, it assigns an "individual score" to each subsequence of appropriate length within the input sequences using the initial PSSM. Second, it computes an E-value from each individual score, to assess the agreement between the corresponding subsequence and the PSSM. Third, it permits subsequences with E-values falling below a threshold to contribute to the underlying PSSM, which is then updated using the Bayesian calculus. A-GLAM iterates its scanning step to convergence, at which point no new subsequences contribute to the PSSM. After convergence, A-GLAM reports predicted regulatory elements within each sequence in order of increasing E-values, so users have a statistical evaluation of the predicted elements in a convenient presentation. Thus, although the Gibbs sampling step in A-GLAM finds at most one regulatory element per input sequence, the scanning step can now rapidly locate further instances of the element in each sequence. Conclusion Datasets from experiments determining the binding sites of transcription factors were used to evaluate the improvement to A-GLAM. Typically, the datasets included several sequences containing multiple instances of a regulatory motif. The improvements to A-GLAM permitted it to predict the multiple instances. PMID:16961919

  6. Kennedy Space Center Director Update

    NASA Image and Video Library

    2014-03-06

    CAPE CANAVERAL, Fla. - Community leaders, business executives, educators, and state and local government leaders were updated on NASA Kennedy Space Center programs and accomplishments during KSC Center Director Bob Cabana’s Center Director Update at the Debus Center at the Kennedy Space Center Visitor Complex in Florida. Attendees talked with Cabana and other senior Kennedy managers and visited displays featuring updates on Kennedy programs and projects, including International Space Station, Commercial Crew, Ground System Development and Operations, Launch Services, Center Planning and Development, Technology, KSC Swamp Works and NASA Education. The morning concluded with a tour of the new Space Shuttle Atlantis exhibit at the visitor complex. For more information, visit http://www.nasa.gov/kennedy. Photo credit: NASA/Daniel Casper

  7. Kennedy Space Center Director Update

    NASA Image and Video Library

    2014-03-06

    CAPE CANAVERAL, Fla. - Community leaders, business executives, educators, and state and local government leaders were updated on NASA Kennedy Space Center programs and accomplishments during Center Director Bob Cabana’s Center Director Update at the Debus Center at the Kennedy Space Center Visitor Complex in Florida. Attendees talked with Cabana and other senior Kennedy managers and visited displays featuring updates on Kennedy programs and projects, including International Space Station, Commercial Crew, Ground System Development and Operations, Launch Services, Center Planning and Development, Technology, KSC Swamp Works and NASA Education. The morning concluded with a tour of the new Space Shuttle Atlantis exhibit at the visitor complex. For more information, visit http://www.nasa.gov/kennedy. Photo credit: NASA/Daniel Casper

  8. Identification of key residues for the binding of glucagon to the N-terminal domain of its receptor: an alanine scan and modeling study.

    PubMed

    Prévost, M; Vertongen, P; Waelbroeck, M

    2012-10-01

    Glucagon plays an essential role in the glycemia maintenance during fasting, but also aggravates hyperglycemia in diabetic patients. A series of analogues of glucagon were synthesized replacing each amino acid of the C-terminal region (residues 15-29) with alanine. The residues affecting the binding to the glucagon receptor are found to be located on one face of the glucagon helix. Several 3-dimensional models of the N-terminal domain of the glucagon receptor in complex with its ligand peptide were built and used to analyze the peptide-receptor interface in terms of the nature of the peptide residues and the interactions they form with the receptor. The models suggest that glucagon keeps its native helical structure upon binding, and that a large part of the interface formed with the receptor is hydrophobic. We find that in the C-terminal region, F22, V23, M27, and D15 are the most important residues for peptide binding. They bury a large portion of their solvent accessible surface area and make numerous interactions with the receptor mainly of the hydrophobic type. © Georg Thieme Verlag KG Stuttgart · New York.

  9. MedlinePlus FAQ: How Often MedlinePlus is Updated

    MedlinePlus

    ... System Pharmacists is updated monthly. Natural Medicines Comprehensive Database Consumer Version is updated quarterly. Medical Encyclopedia: Updated monthly. ... Guidelines Viewers & Players MedlinePlus Connect for ...

  10. Lumbar spine CT scan

    MedlinePlus

    CAT scan - lumbar spine; Computed axial tomography scan - lumbar spine; Computed tomography scan - lumbar spine; CT - lower back ... CT scans rapidly makes detailed pictures of the lower back. The test may be used to look for: ...

  11. Receptor-receptor interactions within receptor mosaics. Impact on neuropsychopharmacology.

    PubMed

    Fuxe, K; Marcellino, D; Rivera, A; Diaz-Cabiale, Z; Filip, M; Gago, B; Roberts, D C S; Langel, U; Genedani, S; Ferraro, L; de la Calle, A; Narvaez, J; Tanganelli, S; Woods, A; Agnati, L F

    2008-08-01

    Future therapies for diseases associated with altered dopaminergic signaling, including Parkinson's disease, schizophrenia and drug addiction or drug dependence may substantially build on the existence of intramembrane receptor-receptor interactions within dopamine receptor containing receptor mosaics (RM; dimeric or high-order receptor oligomers) where it is believed that the dopamine D(2) receptor may operate as the 'hub receptor' within these complexes. The constitutive adenosine A(2A)/dopamine D(2) RM, located in the dorsal striato-pallidal GABA neurons, are of particular interest in view of the demonstrated antagonistic A(2A)/D(2) interaction within these heteromers; an interaction that led to the suggestion and later demonstration that A(2A) antagonists could be used as novel anti-Parkinsonian drugs. Based on the likely existence of A(2A)/D(2)/mGluR5 RM located both extrasynaptically on striato-pallidal GABA neurons and on cortico-striatal glutamate terminals, multiple receptor-receptor interactions within this RM involving synergism between A(2A)/mGluR5 to counteract D(2) signaling, has led to the proposal of using combined mGluR5 and A(2A) antagonists as a future anti-Parkinsonian treatment. Based on the same RM in the ventral striato-pallidal GABA pathways, novel strategies for the treatment of schizophrenia, building on the idea that A(2A) agonists and/or mGluR5 agonists will help reduce the increased dopaminergic signaling associated with this disease, have been suggested. Such treatment may ensure the proper glutamatergic drive from the mediodorsal thalamic nucleus to the prefrontal cortex, one which is believed to be reduced in schizophrenia due to a dominance of D(2)-like signaling in the ventral striatum. Recently, A(2A) receptors also have been shown to counteract the locomotor and sensitizing actions of cocaine and increases in A(2A) receptors have also been observed in the nucleus accumbens after extended cocaine self-administration, probably

  12. Contextual Information Drives the Reconsolidation-Dependent Updating of Retrieved Fear Memories

    PubMed Central

    Jarome, Timothy J; Ferrara, Nicole C; Kwapis, Janine L; Helmstetter, Fred J

    2015-01-01

    Stored memories enter a temporary state of vulnerability following retrieval known as ‘reconsolidation', a process that can allow memories to be modified to incorporate new information. Although reconsolidation has become an attractive target for treatment of memories related to traumatic past experiences, we still do not know what new information triggers the updating of retrieved memories. Here, we used biochemical markers of synaptic plasticity in combination with a novel behavioral procedure to determine what was learned during memory reconsolidation under normal retrieval conditions. We eliminated new information during retrieval by manipulating animals' training experience and measured changes in proteasome activity and GluR2 expression in the amygdala, two established markers of fear memory lability and reconsolidation. We found that eliminating new contextual information during the retrieval of memories for predictable and unpredictable fear associations prevented changes in proteasome activity and glutamate receptor expression in the amygdala, indicating that this new information drives the reconsolidation of both predictable and unpredictable fear associations on retrieval. Consistent with this, eliminating new contextual information prior to retrieval prevented the memory-impairing effects of protein synthesis inhibitors following retrieval. These results indicate that under normal conditions, reconsolidation updates memories by incorporating new contextual information into the memory trace. Collectively, these results suggest that controlling contextual information present during retrieval may be a useful strategy for improving reconsolidation-based treatments of traumatic memories associated with anxiety disorders such as post-traumatic stress disorder. PMID:26062788

  13. Frontal D2/3 Receptor Availability in Schizophrenia Patients Before and After Their First Antipsychotic Treatment: Relation to Cognitive Functions and Psychopathology.

    PubMed

    Nørbak-Emig, Henrik; Ebdrup, Bjørn H; Fagerlund, Birgitte; Svarer, Claus; Rasmussen, Hans; Friberg, Lars; Allerup, Peter N; Rostrup, Egill; Pinborg, Lars H; Glenthøj, Birte Y

    2016-05-01

    We have previously reported associations between frontal D2/3 receptor binding potential positive symptoms and cognitive deficits in antipsychotic-naïve schizophrenia patients. Here, we examined the effect of dopamine D2/3 receptor blockade on cognition. Additionally, we explored the relation between frontal D2/3 receptor availability and treatment effect on positive symptoms. Twenty-five antipsychotic-naïve first-episode schizophrenia patients were examined with the Positive and Negative Syndrome Scale, tested with the cognitive test battery Cambridge Neuropsychological Test Automated Battery, scanned with single-photon emission computerized tomography using the dopamine D2/3 receptor ligand [(123)I]epidepride, and scanned with MRI. After 3 months of treatment with either risperidone (n=13) or zuclopenthixol (n=9), 22 patients were reexamined. Blockade of extrastriatal dopamine D2/3 receptors was correlated with decreased attentional focus (r = -0.615, P=.003) and planning time (r = -0.436, P=.048). Moreover, baseline frontal dopamine D2/3 binding potential and positive symptom reduction correlated positively (D2/3 receptor binding potential left frontal cortex rho = 0.56, P=.003; D2/3 receptor binding potential right frontal cortex rho = 0.48, P=.016). Our data support the hypothesis of a negative influence of D2/3 receptor blockade on specific cognitive functions in schizophrenia. This is highly clinically relevant given the well-established association between severity of cognitive disturbances and a poor functional outcome in schizophrenia. Additionally, the findings support associations between frontal D2/3 receptor binding potential at baseline and the effect of antipsychotic treatment on positive symptoms. © The Author 2016. Published by Oxford University Press on behalf of CINP.

  14. Updates to Enhanced Geothermal System Resource Potential Estimate

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Augustine, Chad

    The deep EGS electricity generation resource potential estimate maintained by the National Renewable Energy Laboratory was updated using the most recent temperature-at-depth maps available from the Southern Methodist University Geothermal Laboratory. The previous study dates back to 2011 and was developed using the original temperature-at-depth maps showcased in the 2006 MIT Future of Geothermal Energy report. The methodology used to update the deep EGS resource potential is the same as in the previous study and is summarized in the paper. The updated deep EGS resource potential estimate was calculated for depths between 3 and 7 km and is binned inmore » 25 degrees C increments. The updated deep EGS electricity generation resource potential estimate is 4,349 GWe. A comparison of the estimates from the previous and updated studies shows a net increase of 117 GWe in the 3-7 km depth range, due mainly to increases in the underlying temperature-at-depth estimates from the updated maps.« less

  15. Postprocessing Algorithm for Driving Conventional Scanning Tunneling Microscope at Fast Scan Rates.

    PubMed

    Zhang, Hao; Li, Xianqi; Chen, Yunmei; Park, Jewook; Li, An-Ping; Zhang, X-G

    2017-01-01

    We present an image postprocessing framework for Scanning Tunneling Microscope (STM) to reduce the strong spurious oscillations and scan line noise at fast scan rates and preserve the features, allowing an order of magnitude increase in the scan rate without upgrading the hardware. The proposed method consists of two steps for large scale images and four steps for atomic scale images. For large scale images, we first apply for each line an image registration method to align the forward and backward scans of the same line. In the second step we apply a "rubber band" model which is solved by a novel Constrained Adaptive and Iterative Filtering Algorithm (CIAFA). The numerical results on measurement from copper(111) surface indicate the processed images are comparable in accuracy to data obtained with a slow scan rate, but are free of the scan drift error commonly seen in slow scan data. For atomic scale images, an additional first step to remove line-by-line strong background fluctuations and a fourth step of replacing the postprocessed image by its ranking map as the final atomic resolution image are required. The resulting image restores the lattice image that is nearly undetectable in the original fast scan data.

  16. Postprocessing Algorithm for Driving Conventional Scanning Tunneling Microscope at Fast Scan Rates

    PubMed Central

    Zhang, Hao; Li, Xianqi; Park, Jewook; Li, An-Ping

    2017-01-01

    We present an image postprocessing framework for Scanning Tunneling Microscope (STM) to reduce the strong spurious oscillations and scan line noise at fast scan rates and preserve the features, allowing an order of magnitude increase in the scan rate without upgrading the hardware. The proposed method consists of two steps for large scale images and four steps for atomic scale images. For large scale images, we first apply for each line an image registration method to align the forward and backward scans of the same line. In the second step we apply a “rubber band” model which is solved by a novel Constrained Adaptive and Iterative Filtering Algorithm (CIAFA). The numerical results on measurement from copper(111) surface indicate the processed images are comparable in accuracy to data obtained with a slow scan rate, but are free of the scan drift error commonly seen in slow scan data. For atomic scale images, an additional first step to remove line-by-line strong background fluctuations and a fourth step of replacing the postprocessed image by its ranking map as the final atomic resolution image are required. The resulting image restores the lattice image that is nearly undetectable in the original fast scan data. PMID:29362664

  17. Clathrin-dependent internalization of the angiotensin II AT₁A receptor links receptor internalization to COX-2 protein expression in rat aortic vascular smooth muscle cells.

    PubMed

    Morinelli, Thomas A; Walker, Linda P; Velez, Juan Carlos Q; Ullian, Michael E

    2015-02-05

    The major effects of Angiotensin II (AngII) in vascular tissue are mediated by AngII AT1A receptor activation. Certain effects initiated by AT1A receptor activation require receptor internalization. In rat aortic vascular smooth muscle cells (RASMC), AngII stimulates cyclooxygenase 2 protein expression. We have previously shown this is mediated by β-arrestin-dependent receptor internalization and NF-κB activation. In this study, a specific inhibitor of clathrin-mediated endocytosis (CME), pitstop-2, was used to test the hypothesis that clathrin-dependent internalization of activated AT1A receptor mediates NF-κB activation and subsequent cyclooxygenase 2 expression. Radioligand binding assays, real time qt-PCR and immunoblotting were used to document the effects of pitstop-2 on AngII binding and signaling in RASMC. Laser scanning confocal microscopy (LSCM) was used to image pitstop-2׳s effects on AT1 receptor/GFP internalization in HEK-293 cells and p65 NF-κB nuclear localization in RASMC. Pitstop-2 significantly inhibited internalization of AT1A receptor (44.7% ± 3.1% Control vs. 13.2% ± 8.3% Pitstop-2; n=3) as determined by radioligand binding studies in RASMC. Studies utilizing AT1A receptor/GFP expressed in HEK 293 cells and LSCM confirmed these findings. Pitstop-2 significantly inhibited AngII-induced p65 NF-κB phosphorylation and nuclear localization, COX-2 message and protein expression in RASMC without altering activation of p42/44 ERK or TNFα signaling. Pitstop-2, a specific inhibitor of clathrin-mediated endocytosis, confirms that internalization of activated AT1A receptor mediates AngII activation of cyclooxygenase 2 expression in RASMC. These data provide support for additional intracellular signaling pathways activated through β-arrestin mediated internalization of G protein-coupled receptors, such as AT1A receptors. Copyright © 2014 Elsevier B.V. All rights reserved.

  18. 77 FR 10650 - Annual Update of Filing Fees

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-02-23

    ... updating is to adjust the fees on the basis of the Commission's costs for Fiscal Year 2011. DATES... establishing updated fees on the basis of the Commission's Fiscal Year 2011 costs. The adjusted fees announced...] Annual Update of Filing Fees AGENCY: Federal Energy Regulatory Commission, DOE. ACTION: Final rule...

  19. 78 FR 2880 - Annual Update of Filing Fees

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-01-15

    ... updating is to adjust the fees on the basis of the Commission's costs for Fiscal Year 2012. DATES... establishing updated fees on the basis of the Commission's Fiscal Year 2012 costs. The adjusted fees announced...] Annual Update of Filing Fees AGENCY: Federal Energy Regulatory Commission, DOE. ACTION: Final rule...

  20. Kennedy Space Center Director Update

    NASA Image and Video Library

    2014-03-06

    CAPE CANAVERAL, Fla. - Community leaders, business executives, educators, and state and local government leaders were updated on NASA Kennedy Space Center programs and accomplishments during Center Director Bob Cabana’s Center Director Update at the Debus Center at the Kennedy Space Center Visitor Complex in Florida. Rob Mueller, senior technologist, talks with attendees at the Swamp Works display. Attendees talked with Cabana and other senior Kennedy managers and visited displays featuring updates on Kennedy programs and projects, including International Space Station, Commercial Crew, Ground System Development and Operations, Launch Services, Center Planning and Development, Technology, KSC Swamp Works and NASA Education. The morning concluded with a tour of the new Space Shuttle Atlantis exhibit at the visitor complex. For more information, visit http://www.nasa.gov/kennedy. Photo credit: NASA/Daniel Casper

  1. Kennedy Space Center Director Update

    NASA Image and Video Library

    2014-03-06

    CAPE CANAVERAL, Fla. - Community leaders, business executives, educators, and state and local government leaders were updated on NASA Kennedy Space Center programs and accomplishments during Center Director Bob Cabana’s Center Director Update at the Debus Center at the Kennedy Space Center Visitor Complex in Florida. Rob Mueller, a senior technologist, talks to an attendee about Kennedy’s Swamp Works Laboratory. Attendees talked with Cabana and other senior Kennedy managers and visited displays featuring updates on Kennedy programs and projects, including International Space Station, Commercial Crew, Ground System Development and Operations, Launch Services, Center Planning and Development, Technology, KSC Swamp Works and NASA Education. The morning concluded with a tour of the new Space Shuttle Atlantis exhibit at the visitor complex. For more information, visit http://www.nasa.gov/kennedy. Photo credit: NASA/Daniel Casper

  2. The changing world of G protein-coupled receptors: from monomers to dimers and receptor mosaics with allosteric receptor-receptor interactions.

    PubMed

    Fuxe, Kjell; Marcellino, Daniel; Borroto-Escuela, Dasiel Oscar; Frankowska, Malgorzata; Ferraro, Luca; Guidolin, Diego; Ciruela, Francisco; Agnati, Luigi F

    2010-10-01

    Based on indications of direct physical interactions between neuropeptide and monoamine receptors in the early 1980s, the term receptor-receptor interactions was introduced and later on the term receptor heteromerization in the early 1990s. Allosteric mechanisms allow an integrative activity to emerge either intramolecularly in G protein-coupled receptor (GPCR) monomers or intermolecularly via receptor-receptor interactions in GPCR homodimers, heterodimers, and receptor mosaics. Stable heteromers of Class A receptors may be formed that involve strong high energy arginine-phosphate electrostatic interactions. These receptor-receptor interactions markedly increase the repertoire of GPCR recognition, signaling and trafficking in which the minimal signaling unit in the GPCR homomers appears to be one receptor and one G protein. GPCR homomers and GPCR assemblies are not isolated but also directly interact with other proteins to form horizontal molecular networks at the plasma membrane.

  3. Fourier transform coupled tryptophan scanning mutagenesis identifies a bending point on the lipid-exposed δM3 transmembrane domain of the Torpedo californica nicotinic acetylcholine receptor

    PubMed Central

    Caballero-Rivera, Daniel; Cruz-Nieves, Omar A; Oyola-Cintrón, Jessica; Torres-Núñez, David A; Otero-Cruz, José D

    2011-01-01

    The nicotinic acetylcholine receptor (nAChR) is a member of a family of ligand-gated ion channels that mediate diverse physiological functions, including fast synaptic transmission along the peripheral and central nervous systems. Several studies have made significant advances toward determining the structure and dynamics of the lipid-exposed domains of the nAChR. However, a high-resolution atomic structure of the nAChR still remains elusive. In this study, we extended the Fourier transform coupled tryptophan scanning mutagenesis (FT-TrpScanM) approach to gain insight into the secondary structure of the δM3 transmembrane domain of the Torpedo californica nAChR, to monitor conformational changes experienced by this domain during channel gating, and to identify which lipid-exposed positions are linked to the regulation of ion channel kinetics. The perturbations produced by periodic tryptophan substitutions along the δM3 transmembrane domain were characterized by two-electrode voltage clamp and 125I-labeled α-bungarotoxin binding assays. The periodicity profiles and Fourier transform spectra of this domain revealed similar helical structures for the closed- and open-channel states. However, changes in the oscillation patterns observed between positions Val-299 and Val-304 during transition between the closed- and open-channel states can be explained by the structural effects caused by the presence of a bending point introduced by a Thr-Gly motif at positions 300–301. The changes in periodicity and localization of residues between the closed-and open-channel states could indicate a structural transition between helix types in this segment of the domain. Overall, the data further demonstrate a functional link between the lipid-exposed transmembrane domain and the nAChR gating machinery. PMID:21785268

  4. Mechanism of Activation of Enteric Nociceptive Neurons via Interaction of TLR4 and TRPV1 Receptors.

    PubMed

    Filippova, L V; Fedorova, A V; Nozdrachev, A D

    2018-03-01

    Evidence obtained by immunohistochemical double labeling and confocal laser scanning microscopy suggests that capsaicin, a ligand of the TRPV1 nociceptive vanilloid receptor, increases the number of TLR4-positive neurons in the rat colon myenteric plexus. In colitis caused by trinitrobenzene sulfonate, an increase in TRPV1 expression was more significant in both plexuses. Specific inhibitor of the TLR4 (C34) pattern-recognition receptor reduces TRPV1 expression in enteric neurons of both intact rats and rats with induced acute colitis. Thus, stimulation of nociceptive neurons by means of direct activation of their receptors of innate immunity (TLR4) is one of the possible mechanisms underlying the visceral pain in bacterial invasion and inflammatory bowel diseases.

  5. 10 CFR 26.57 - Authorization update.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 10 Energy 1 2011-01-01 2011-01-01 false Authorization update. 26.57 Section 26.57 Energy NUCLEAR REGULATORY COMMISSION FITNESS FOR DUTY PROGRAMS Granting and Maintaining Authorization § 26.57 Authorization update. (a) Before granting authorization to an individual whose authorization has been interrupted for...

  6. 10 CFR 26.57 - Authorization update.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 10 Energy 1 2010-01-01 2010-01-01 false Authorization update. 26.57 Section 26.57 Energy NUCLEAR REGULATORY COMMISSION FITNESS FOR DUTY PROGRAMS Granting and Maintaining Authorization § 26.57 Authorization update. (a) Before granting authorization to an individual whose authorization has been interrupted for...

  7. 10 CFR 26.57 - Authorization update.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 10 Energy 1 2013-01-01 2013-01-01 false Authorization update. 26.57 Section 26.57 Energy NUCLEAR REGULATORY COMMISSION FITNESS FOR DUTY PROGRAMS Granting and Maintaining Authorization § 26.57 Authorization update. (a) Before granting authorization to an individual whose authorization has been interrupted for...

  8. 10 CFR 26.57 - Authorization update.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 10 Energy 1 2014-01-01 2014-01-01 false Authorization update. 26.57 Section 26.57 Energy NUCLEAR REGULATORY COMMISSION FITNESS FOR DUTY PROGRAMS Granting and Maintaining Authorization § 26.57 Authorization update. (a) Before granting authorization to an individual whose authorization has been interrupted for...

  9. 10 CFR 26.57 - Authorization update.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 10 Energy 1 2012-01-01 2012-01-01 false Authorization update. 26.57 Section 26.57 Energy NUCLEAR REGULATORY COMMISSION FITNESS FOR DUTY PROGRAMS Granting and Maintaining Authorization § 26.57 Authorization update. (a) Before granting authorization to an individual whose authorization has been interrupted for...

  10. Correcting nonlinear drift distortion of scanning probe and scanning transmission electron microscopies from image pairs with orthogonal scan directions

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Ophus, Colin; Ciston, Jim; Nelson, Chris T.

    Unwanted motion of the probe with respect to the sample is a ubiquitous problem in scanning probe and scanning transmission electron microscopies, causing both linear and nonlinear artifacts in experimental images. We have designed a procedure to correct these artifacts by using orthogonal scan pairs to align each measurement line-by-line along the slow scan direction, by fitting contrast variation along the lines. We demonstrate the accuracy of our algorithm on both synthetic and experimental data and provide an implementation of our method.

  11. Correcting nonlinear drift distortion of scanning probe and scanning transmission electron microscopies from image pairs with orthogonal scan directions

    DOE PAGES

    Ophus, Colin; Ciston, Jim; Nelson, Chris T.

    2015-12-10

    Unwanted motion of the probe with respect to the sample is a ubiquitous problem in scanning probe and scanning transmission electron microscopies, causing both linear and nonlinear artifacts in experimental images. We have designed a procedure to correct these artifacts by using orthogonal scan pairs to align each measurement line-by-line along the slow scan direction, by fitting contrast variation along the lines. We demonstrate the accuracy of our algorithm on both synthetic and experimental data and provide an implementation of our method.

  12. Updated results from MONALEESA-2, a phase III trial of first-line ribociclib plus letrozole versus placebo plus letrozole in hormone receptor-positive, HER2-negative advanced breast cancer.

    PubMed

    Hortobagyi, G N; Stemmer, S M; Burris, H A; Yap, Y S; Sonke, G S; Paluch-Shimon, S; Campone, M; Petrakova, K; Blackwell, K L; Winer, E P; Janni, W; Verma, S; Conte, P; Arteaga, C L; Cameron, D A; Mondal, S; Su, F; Miller, M; Elmeliegy, M; Germa, C; O'Shaughnessy, J

    2018-04-27

    The phase III MONALEESA-2 study demonstrated significantly prolonged progression-free survival (PFS) and a manageable toxicity profile for first-line ribociclib plus letrozole versus placebo plus letrozole in patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer. Here we report updated efficacy and safety data, together with exploratory biomarker analyses, from the MONALEESA-2 study. A total of 668 postmenopausal women with HR+, HER2- recurrent/metastatic breast cancer were randomized (1:1; stratified by presence/absence of liver and/or lung metastases) to ribociclib (600 mg/day; 3-weeks-on/1-week-off; 28-day treatment cycles) plus letrozole (2.5 mg/day; continuous) or placebo plus letrozole. The primary endpoint was locally assessed PFS. The key secondary endpoint was overall survival (OS). Other secondary endpoints included overall response rate (ORR) and safety. Biomarker analysis was an exploratory endpoint. At the time of the second interim analysis, the median duration of follow-up was 26.4 months. Median PFS was 25.3 months (95% confidence interval [CI], 23.0-30.3) for ribociclib plus letrozole and 16.0 months (95% CI, 13.4-18.2) for placebo plus letrozole (hazard ratio 0.568; 95% CI, 0.457-0.704; log-rank P=9.63 × 10-8). Ribociclib treatment benefit was maintained irrespective of PIK3CA or TP53 mutation status, total Rb, Ki67, or p16 protein expression, and CDKN2A, CCND1, or ESR1 mRNA levels. Ribociclib benefit was more pronounced in patients with wild-type versus altered receptor tyrosine kinase genes. OS data remain immature, with 116 deaths observed; 50 in the ribociclib arm and 66 in the placebo arm (hazard ratio: 0.746; 95% CI, 0.517-1.078). The ORR was 42.5% versus 28.7% for all patients treated with ribociclib plus letrozole versus placebo plus letrozole, respectively, and 54.5% versus 38.8%, respectively, for patients with measurable disease. Safety results, after a

  13. Combining Multi-Source Remotely Sensed Data and a Process-Based Model for Forest Aboveground Biomass Updating.

    PubMed

    Lu, Xiaoman; Zheng, Guang; Miller, Colton; Alvarado, Ernesto

    2017-09-08

    Monitoring and understanding the spatio-temporal variations of forest aboveground biomass (AGB) is a key basis to quantitatively assess the carbon sequestration capacity of a forest ecosystem. To map and update forest AGB in the Greater Khingan Mountains (GKM) of China, this work proposes a physical-based approach. Based on the baseline forest AGB from Landsat Enhanced Thematic Mapper Plus (ETM+) images in 2008, we dynamically updated the annual forest AGB from 2009 to 2012 by adding the annual AGB increment (ABI) obtained from the simulated daily and annual net primary productivity (NPP) using the Boreal Ecosystem Productivity Simulator (BEPS) model. The 2012 result was validated by both field- and aerial laser scanning (ALS)-based AGBs. The predicted forest AGB for 2012 estimated from the process-based model can explain 31% ( n = 35, p < 0.05, RMSE = 2.20 kg/m²) and 85% ( n = 100, p < 0.01, RMSE = 1.71 kg/m²) of variation in field- and ALS-based forest AGBs, respectively. However, due to the saturation of optical remote sensing-based spectral signals and contribution of understory vegetation, the BEPS-based AGB tended to underestimate/overestimate the AGB for dense/sparse forests. Generally, our results showed that the remotely sensed forest AGB estimates could serve as the initial carbon pool to parameterize the process-based model for NPP simulation, and the combination of the baseline forest AGB and BEPS model could effectively update the spatiotemporal distribution of forest AGB.

  14. Combining Multi-Source Remotely Sensed Data and a Process-Based Model for Forest Aboveground Biomass Updating

    PubMed Central

    Lu, Xiaoman; Zheng, Guang; Miller, Colton

    2017-01-01

    Monitoring and understanding the spatio-temporal variations of forest aboveground biomass (AGB) is a key basis to quantitatively assess the carbon sequestration capacity of a forest ecosystem. To map and update forest AGB in the Greater Khingan Mountains (GKM) of China, this work proposes a physical-based approach. Based on the baseline forest AGB from Landsat Enhanced Thematic Mapper Plus (ETM+) images in 2008, we dynamically updated the annual forest AGB from 2009 to 2012 by adding the annual AGB increment (ABI) obtained from the simulated daily and annual net primary productivity (NPP) using the Boreal Ecosystem Productivity Simulator (BEPS) model. The 2012 result was validated by both field- and aerial laser scanning (ALS)-based AGBs. The predicted forest AGB for 2012 estimated from the process-based model can explain 31% (n = 35, p < 0.05, RMSE = 2.20 kg/m2) and 85% (n = 100, p < 0.01, RMSE = 1.71 kg/m2) of variation in field- and ALS-based forest AGBs, respectively. However, due to the saturation of optical remote sensing-based spectral signals and contribution of understory vegetation, the BEPS-based AGB tended to underestimate/overestimate the AGB for dense/sparse forests. Generally, our results showed that the remotely sensed forest AGB estimates could serve as the initial carbon pool to parameterize the process-based model for NPP simulation, and the combination of the baseline forest AGB and BEPS model could effectively update the spatiotemporal distribution of forest AGB. PMID:28885556

  15. Ultrastructure studies on the papillae and the nonciliated sensory receptors of adult Spirometra erinacei (Cestoda, Pseudophyllidea).

    PubMed

    Okino, T; Hatsushika, R

    1994-01-01

    The small numerous papillae on the ventral surface of the gravid proglottid of adult Spirometra erinacei were studied by scanning electron microscopy. The arrangement of clumps of papillae was recognized on the surface of the central portion around the genital atrium, with lateral clumps being located above a pair of longitudinal nerve cords and marginal ones, on both sides of the proglottid. By transmission electron microscopy, two types of nonciliated sensory receptors were observed within the papillae. The type I, single receptor was embedded within a papilla. This dome-like sensory receptor contained two electron-dense collars and four rootlets surrounded by numerous thin filaments. The type II receptor was found arranged in groups in the area between the papillae, and the apical end was exposed to the external environment. This simple, club-like sensory receptor contained electron-lucent vesicles and microtubules. We believe that the papillae play an important role in cross-insemination.

  16. Behavioral, biological, and chemical perspectives on targeting CRF1 receptor antagonists to treat alcoholism

    PubMed Central

    Zorrilla, Eric P.; Heilig, Markus; de Wit, Harriet; Shaham, Yavin

    2013-01-01

    Background Alcohol use disorders are chronic disabling conditions for which existing pharmacotherapies have only modest efficacy. In the present review, derived from the 2012 Behavior, Biology and Chemistry “Translational Research in Addiction” symposium, we summarize the anti-relapse potential of corticotropin-releasing factor type 1 (CRF1) receptor antagonists to reduce negative emotional symptoms of acute and protracted alcohol withdrawal and stress-induced relapse to alcohol seeking. Methods We review the biology of CRF1 systems, the activity of CRF1 receptor antagonists in animal models of anxiolytic and antidepressant activity, and experimental findings in alcohol addiction models. We also update the clinical trial status of CRF1 receptor antagonists, including pexacerfont (BMS-562086), emicerfont (GW876008), verucerfont (GSK561679), CP316311, SSR125543A, R121919/NBI30775, R317573/19567470/CRA5626, and ONO-2333Ms. Finally, we discuss the potential heterogeneity and pharmacogenomics of CRF1 receptor pharmacotherapy for alcohol dependence. Results The evidence suggests that brain penetrant-CRF1 receptor antagonists have therapeutic potential for alcohol dependence. Lead compounds with clinically desirable pharmacokinetic properties now exist, and longer receptor residence rates (i.e., slow dissociation) may predict greater CRF1 receptor antagonist efficacy. Functional variants in genes that encode CRF system molecules, including polymorphisms in Crhr1 (rs110402, rs1876831, rs242938) and Crhbp genes (rs10055255, rs3811939) may promote alcohol seeking and consumption by altering basal or stress-induced CRF system activation. Conclusions Ongoing clinical trials with pexacerfont and verucerfont in moderately to highly severe dependent anxious alcoholics may yield insight as to the role of CRF1 receptor antagonists in a personalized medicine approach to treat drug or alcohol dependence. PMID:23294766

  17. Update in Internal Medicine

    PubMed Central

    López-Jiménez, Francisco; Brito, Máximo; Aude, Y. Wady; Scheinberg, Phillip; Kaplan, Mariana; Dixon, Denise A.; Schneiderman, Neil; Trejo, Jorge F.; López-Salazar, Luis Humberto; Ramírez-Barba, Ector Jaime; Kalil, Roberto; Ortiz, Carmen; Goyos, José; Buenaño, Alvaro; Kottiech, Samer; Lamas, Gervasio A.

    2009-01-01

    More than 500,000 new medical articles are published every year and available time to keep updated is scarcer every day. Nowadays, the task of selecting useful, consistent, and relevant information for clinicians is a priority in many major medical journals. This review has the aim of gathering the results of the most important findings in clinical medicine in the last few years. It is focused on results from randomized clinical trials and well-designed observational research. Findings were included preferentially if they showed solid results, and we avoided as much as possible including only preliminary data, or results that included only non-clinical outcomes. Some of the most relevant findings reported here include the significant benefit of statins in patients with coronary artery disease even with mean cholesterol level. It also provides a substantial review of the most significant trials assessing the effectiveness of IIb/IIIa receptor blockers. In gastroenterology many advances have been made in the H. pylori eradication, and the finding that the cure of H. pylori infection may be followed by gastroesophageal reflux disease. Some new antivirals have shown encouraging results in patients with chronic hepatitis. In the infectious disease arena, the late breaking trials in anti-retroviral disease are discussed, as well as the new trends regarding antibiotic resistance. This review approaches also the role of leukotriene modifiers in the treatment of asthma and discusses the benefit of using methylprednisolone in patients with adult respiratory distress syndrome, among many other advances in internal medicine. PMID:11068074

  18. How Documentalists Update SIMBAD

    NASA Astrophysics Data System (ADS)

    Buga, M.; Bot, C.; Brouty, M.; Bruneau, C.; Brunet, C.; Cambresy, L.; Eisele, A.; Genova, F.; Lesteven, S.; Loup, C.; Neuville, M.; Oberto, A.; Ochsenbein, F.; Perret, E.; Siebert, A.; Son, E.; Vannier, P.; Vollmer, B.; Vonflie, P.; Wenger, M.; Woelfel, F.

    2015-04-01

    The Strasbourg astronomical Data Center (CDS) was created in 1972 and has had a major role in astronomy for more than forty years. CDS develops a service called SIMBAD that provides basic data, cross-identifications, bibliography, and measurements for astronomical objects outside the solar system. It brings to the scientific community an added value to content which is updated daily by a team of documentalists working together in close collaboration with astronomers and IT specialists. We explain how the CDS staff updates SIMBAD with object citations in the main astronomical journals, as well as with astronomical data and measurements. We also explain how the identification is made between the objects found in the literature and those already existing in SIMBAD. We show the steps followed by the documentalist team to update the database using different tools developed at CDS, like the sky visualizer Aladin, and the large catalogues and survey database VizieR. As a direct result of this teamwork, SIMBAD integrates almost 10.000 bibliographic references per year. The service receives more than 400.000 queries per day.

  19. [2015 updated position statement of the management of hyperglycaemia in type 2 diabetes].

    PubMed

    Scheen, A J; Paquot, N

    2015-08-26

    The strategy for the management ot type 2 diabetes, summarized by a group of European and American experts, has been updated early 2015. A patient-centered approach is recommended and the first drug choice is metformin combined with lifestyle improvement. After failure of metformin monotherapy, the selection of a second drug should be based on the efficacy, safety and cost of each pharmacological class. When compared to the position statement of 2012, the most important changes are the possible addition of a gliptin to a dual oral therapy or even to insulin, the commercialization of sodium-glucose cotransporters type 2 (SGLT2) inhibitors (gliflozins, to be used in dual or triple therapy, even in combination with insulin) and the possible combination of a glucagon-like peptide-I receptor agonist together with a basal insulin.

  20. A High Rigidity and Precision Scanning Tunneling Microscope with Decoupled XY and Z Scans

    PubMed Central

    Chen, Xu; Guo, Tengfei; Hou, Yubin; Zhang, Jing

    2017-01-01

    A new scan-head structure for the scanning tunneling microscope (STM) is proposed, featuring high scan precision and rigidity. The core structure consists of a piezoelectric tube scanner of quadrant type (for XY scans) coaxially housed in a piezoelectric tube with single inner and outer electrodes (for Z scan). They are fixed at one end (called common end). A hollow tantalum shaft is coaxially housed in the XY-scan tube and they are mutually fixed at both ends. When the XY scanner scans, its free end will bring the shaft to scan and the tip which is coaxially inserted in the shaft at the common end will scan a smaller area if the tip protrudes short enough from the common end. The decoupled XY and Z scans are desired for less image distortion and the mechanically reduced scan range has the superiority of reducing the impact of the background electronic noise on the scanner and enhancing the tip positioning precision. High quality atomic resolution images are also shown. PMID:29270242

  1. A High Rigidity and Precision Scanning Tunneling Microscope with Decoupled XY and Z Scans.

    PubMed

    Chen, Xu; Guo, Tengfei; Hou, Yubin; Zhang, Jing; Meng, Wenjie; Lu, Qingyou

    2017-01-01

    A new scan-head structure for the scanning tunneling microscope (STM) is proposed, featuring high scan precision and rigidity. The core structure consists of a piezoelectric tube scanner of quadrant type (for XY scans) coaxially housed in a piezoelectric tube with single inner and outer electrodes (for Z scan). They are fixed at one end (called common end). A hollow tantalum shaft is coaxially housed in the XY -scan tube and they are mutually fixed at both ends. When the XY scanner scans, its free end will bring the shaft to scan and the tip which is coaxially inserted in the shaft at the common end will scan a smaller area if the tip protrudes short enough from the common end. The decoupled XY and Z scans are desired for less image distortion and the mechanically reduced scan range has the superiority of reducing the impact of the background electronic noise on the scanner and enhancing the tip positioning precision. High quality atomic resolution images are also shown.

  2. Special raster scanning for reduction of charging effects in scanning electron microscopy.

    PubMed

    Suzuki, Kazuhiko; Oho, Eisaku

    2014-01-01

    A special raster scanning (SRS) method for reduction of charging effects is developed for the field of SEM. Both a conventional fast scan (horizontal direction) and an unusual scan (vertical direction) are adopted for acquiring raw data consisting of many sub-images. These data are converted to a proper SEM image using digital image processing techniques. About sharpness of the image and reduction of charging effects, the SRS is compared with the conventional fast scan (with frame-averaging) and the conventional slow scan. Experimental results show the effectiveness of SRS images. By a successful combination of the proposed scanning method and low accelerating voltage (LV)-SEMs, it is expected that higher-quality SEM images can be more easily acquired by the considerable reduction of charging effects, while maintaining the resolution. © 2013 Wiley Periodicals, Inc.

  3. Lidar arc scan uncertainty reduction through scanning geometry optimization

    NASA Astrophysics Data System (ADS)

    Wang, H.; Barthelmie, R. J.; Pryor, S. C.; Brown, G.

    2015-10-01

    Doppler lidars are frequently operated in a mode referred to as arc scans, wherein the lidar beam scans across a sector with a fixed elevation angle and the resulting measurements are used to derive an estimate of the n minute horizontal mean wind velocity (speed and direction). Previous studies have shown that the uncertainty in the measured wind speed originates from turbulent wind fluctuations and depends on the scan geometry (the arc span and the arc orientation). This paper is designed to provide guidance on optimal scan geometries for two key applications in the wind energy industry: wind turbine power performance analysis and annual energy production. We present a quantitative analysis of the retrieved wind speed uncertainty derived using a theoretical model with the assumption of isotropic and frozen turbulence, and observations from three sites that are onshore with flat terrain, onshore with complex terrain and offshore, respectively. The results from both the theoretical model and observations show that the uncertainty is scaled with the turbulence intensity such that the relative standard error on the 10 min mean wind speed is about 30 % of the turbulence intensity. The uncertainty in both retrieved wind speeds and derived wind energy production estimates can be reduced by aligning lidar beams with the dominant wind direction, increasing the arc span and lowering the number of beams per arc scan. Large arc spans should be used at sites with high turbulence intensity and/or large wind direction variation when arc scans are used for wind resource assessment.

  4. Effect of display update interval, update type, and background on perception of aircraft separation on a cockpit display on traffic information

    NASA Technical Reports Server (NTRS)

    Jago, S.; Baty, D.; Oconnor, S.; Palmer, E.

    1981-01-01

    The concept of a cockpit display of traffic information (CDTI) includes the integration of air traffic, navigation, and other pertinent information in a single electronic display in the cockpit. Concise display symbology was developed for use in later full-mission simulator evaluations of the CDTI concept. Experimental variables used included the update interval motion of the aircraft, the update type, (that is, whether the two aircraft were updated at the same update interval or not), the background (grid pattern or no background), and encounter type (straight or curved). Only the type of encounter affected performance.

  5. Recent Updates of A Multi-Phase Transport (AMPT) Model

    NASA Astrophysics Data System (ADS)

    Lin, Zi-Wei

    2008-10-01

    We will present recent updates to the AMPT model, a Monte Carlo transport model for high energy heavy ion collisions, since its first public release in 2004 and the corresponding detailed descriptions in Phys. Rev. C 72, 064901 (2005). The updates often result from user requests. Some of these updates expand the physics processes or descriptions in the model, while some updates improve the usability of the model such as providing the initial parton distributions or help avoid crashes on some operating systems. We will also explain how the AMPT model is being maintained and updated.

  6. Apparatus for controlling the scan width of a scanning laser beam

    DOEpatents

    Johnson, Gary W.

    1996-01-01

    Swept-wavelength lasers are often used in absorption spectroscopy applications. In experiments where high accuracy is required, it is desirable to continuously monitor and control the range of wavelengths scanned (the scan width). A system has been demonstrated whereby the scan width of a swept ring-dye laser, or semiconductor diode laser, can be measured and controlled in real-time with a resolution better than 0.1%. Scan linearity, or conformity to a nonlinear scan waveform, can be measured and controlled. The system of the invention consists of a Fabry-Perot interferometer, three CAMAC interface modules, and a microcomputer running a simple analysis and proportional-integral control algorithm. With additional modules, multiple lasers can be simultaneously controlled. The invention also includes an embodiment implemented on an ordinary PC with a multifunction plug-in board.

  7. D Scanning of Live Pigs System and its Application in Body Measurements

    NASA Astrophysics Data System (ADS)

    Guo, H.; Wang, K.; Su, W.; Zhu, D. H.; Liu, W. L.; Xing, Ch.; Chen, Z. R.

    2017-09-01

    The shape of a live pig is an important indicator of its health and value, whether for breeding or for carcass quality. This paper implements a prototype system for live single pig body surface 3d scanning based on two consumer depth cameras, utilizing the 3d point clouds data. These cameras are calibrated in advance to have a common coordinate system. The live 3D point clouds stream of moving single pig is obtained by two Xtion Pro Live sensors from different viewpoints simultaneously. A novel detection method is proposed and applied to automatically detect the frames containing pigs with the correct posture from the point clouds stream, according to the geometric characteristics of pig's shape. The proposed method is incorporated in a hybrid scheme, that serves as the preprocessing step in a body measurements framework for pigs. Experimental results show the portability of our scanning system and effectiveness of our detection method. Furthermore, an updated this point cloud preprocessing software for livestock body measurements can be downloaded freely from https://github.com/LiveStockShapeAnalysis to livestock industry, research community and can be used for monitoring livestock growth status.

  8. Preferential binding to dopamine D3 over D2 receptors by cariprazine in patients with schizophrenia using PET with the D3/D2 receptor ligand [(11)C]-(+)-PHNO.

    PubMed

    Girgis, Ragy R; Slifstein, Mark; D'Souza, Deepak; Lee, Yih; Periclou, Antonia; Ghahramani, Parviz; Laszlovszky, István; Durgam, Suresh; Adham, Nika; Nabulsi, Nabeel; Huang, Yiyun; Carson, Richard E; Kiss, Béla; Kapás, Margit; Abi-Dargham, Anissa; Rakhit, Ashok

    2016-10-01

    Second-generation antipsychotics occupy dopamine D2 receptors and act as antagonists or partial agonists at these receptors. While these drugs alleviate positive symptoms in patients with schizophrenia, they are less effective for treating cognitive deficits and negative symptoms. Dopamine D3 receptors are highly expressed in areas of the brain thought to play a role in the regulation of motivation and reward-related behavior. Consequently, the dopamine D3 receptor has become a target for treating negative symptoms in combination with D2 antagonism to treat positive symptoms in patients with schizophrenia. The purpose of this study was to determine the cariprazine receptor occupancies in brain for D2 and D3 receptors in patients with schizophrenia. Using [(11)C]-(+)-PHNO as a radioligand, positron emission tomography (PET) scans were performed in eight patients at baseline and postdose on days 1, 4, and 15. Plasma and cerebrospinal fluid (CSF) samples were analyzed for cariprazine concentrations. A monotonic dose-occupancy relationship was observed for both receptor types. After 2 weeks of treatment, near complete (∼100 %) occupancies were observed for both receptors at a dose of 12 mg/day. At the lowest cariprazine dose (1 mg/day), mean D3 and D2 receptor occupancies were 76 and 45 %, respectively, suggesting selectivity for D3 over D2 receptors at low doses. An exposure-response analysis found a ∼3-fold difference in EC50 (D3 = 3.84 nM and D2 = 13.03 nM) in plasma after 2 weeks of dosing. This PET imaging study in patients with schizophrenia demonstrated that cariprazine is a D3-preferring dual D3/D2 receptor partial agonist.

  9. Environmental scanning electron microscopy gold immunolabeling in cell biology.

    PubMed

    Rosso, Francesco; Papale, Ferdinando; Barbarisi, Alfonso

    2013-01-01

    Immunogold labeling (IGL) technique has been utilized by many authors in combination with scanning electron microscopy (SEM) and transmission electron microscopy (TEM) to obtain the identification/localization of receptors and antigens, both in cells and tissues. Environmental scanning electron microscopy (ESEM) represents an important tool in biomedical research, since it does not require any severe processing of the sample, lowering the risk of generating artifacts and interfere with the IGL procedure. The absence of metal coating could yield further advantages for our purpose as the labeling detection is based on the atomic number difference between nanogold spheres and the biological material. Using the gaseous secondary electron detector, compositional contrast is easily revealed by the backscattered electron component of the signal. In spite of this fact, only few published papers present a combination of ESEM and IGL. Hereby we present our method, optimized to improve the intensity and the specificity of the labeling signal, in order to obtain a semiquantitative evaluation of the labeling signal.In particular, we used a combination of IGL and ESEM to detect the presence of a protein on the cell surface. To achieve this purpose, we chose as an experimental system 3T3 Swiss albino mouse fibroblasts and galectin-3.

  10. Kennedy Space Center Director Update

    NASA Image and Video Library

    2014-03-06

    CAPE CANAVERAL, Fla. - Community leaders, business executives, educators, and state and local government leaders were updated on NASA Kennedy Space Center programs and accomplishments during Center Director Bob Cabana’s Center Director Update at the Debus Center at the Kennedy Space Center Visitor Complex in Florida. At left, Susan Fernandez from the Office of Senator Marco Rubio talks with another attendee near the Education display. Attendees talked with Cabana and other senior Kennedy managers and visited displays featuring updates on Kennedy programs and projects, including International Space Station, Commercial Crew, Ground System Development and Operations, Launch Services, Center Planning and Development, Technology, KSC Swamp Works and NASA Education. The morning concluded with a tour of the new Space Shuttle Atlantis exhibit at the visitor complex. For more information, visit http://www.nasa.gov/kennedy. Photo credit: NASA/Daniel Casper

  11. Kennedy Space Center Director Update

    NASA Image and Video Library

    2014-03-06

    CAPE CANAVERAL, Fla. - Community leaders, business executives, educators, and state and local government leaders were updated on NASA Kennedy Space Center programs and accomplishments during Center Director Bob Cabana’s Center Director Update at the Debus Center at the Kennedy Space Center Visitor Complex in Florida. Attendees mingled and visited various displays, including Ground Systems Development and Operations Program and Education Office displays. Attendees talked with Cabana and other senior Kennedy managers and visited displays featuring updates on Kennedy programs and projects, including International Space Station, Commercial Crew, Ground System Development and Operations, Launch Services, Center Planning and Development, Technology, KSC Swamp Works and NASA Education. The morning concluded with a tour of the new Space Shuttle Atlantis exhibit at the visitor complex. For more information, visit http://www.nasa.gov/kennedy. Photo credit: NASA/Daniel Casper

  12. Kennedy Space Center Director Update

    NASA Image and Video Library

    2014-03-06

    CAPE CANAVERAL, Fla. - Community leaders, business executives, educators, and state and local government leaders were updated on NASA Kennedy Space Center programs and accomplishments during Center Director Bob Cabana’s Center Director Update at the Debus Center at the Kennedy Space Center Visitor Complex in Florida. An attendee talks with engineers Jason Hopkins and Lisa Lutz, at the Ground Systems Development and Operations display. Attendees talked with Cabana and other senior Kennedy managers and visited displays featuring updates on Kennedy programs and projects, including International Space Station, Commercial Crew, Ground System Development and Operations, Launch Services, Center Planning and Development, Technology, KSC Swamp Works and NASA Education. The morning concluded with a tour of the new Space Shuttle Atlantis exhibit at the visitor complex. For more information, visit http://www.nasa.gov/kennedy. Photo credit: NASA/Daniel Casper

  13. Kennedy Space Center Director Update

    NASA Image and Video Library

    2014-03-06

    CAPE CANAVERAL, Fla. - Community leaders, business executives, educators, and state and local government leaders were updated on NASA Kennedy Space Center programs and accomplishments during Center Director Bob Cabana’s Center Director Update at the Debus Center at the Kennedy Space Center Visitor Complex in Florida. An attendee talks with Scott Thurston, Kennedy deputy of the spacecraft office at the Commercial Crew Program display. Attendees talked with Cabana and other senior Kennedy managers and visited displays featuring updates on Kennedy programs and projects, including International Space Station, Commercial Crew, Ground System Development and Operations, Launch Services, Center Planning and Development, Technology, KSC Swamp Works and NASA Education. The morning concluded with a tour of the new Space Shuttle Atlantis exhibit at the visitor complex. For more information, visit http://www.nasa.gov/kennedy. Photo credit: NASA/Daniel Casper

  14. Kennedy Space Center Director Update

    NASA Image and Video Library

    2014-03-06

    CAPE CANAVERAL, Fla. - Community leaders, business executives, educators, and state and local government leaders were updated on NASA Kennedy Space Center programs and accomplishments during Center Director Bob Cabana’s Center Director Update at the Debus Center at the Kennedy Space Center Visitor Complex in Florida. An attendee talks with Trent Smith, program manager, and Tammy Belk, a program specialist, at the ISS Ground Processing and Research Office display. Attendees talked with Cabana and other senior Kennedy managers and visited displays featuring updates on Kennedy programs and projects, including International Space Station, Commercial Crew, Ground System Development and Operations, Launch Services, Center Planning and Development, Technology, KSC Swamp Works and NASA Education. The morning concluded with a tour of the new Space Shuttle Atlantis exhibit at the visitor complex. For more information, visit http://www.nasa.gov/kennedy. Photo credit: NASA/Daniel Casper

  15. NASA Update.

    NASA Image and Video Library

    2011-02-15

    NASA Deputy Administrator Lori Garver answers questions during a NASA Update on, Tuesday, Feb. 15, 2011, at NASA Headquarters in Washington. Garver and NASA Administrator Charles Bolden took the time discuss the agency’s fiscal year 2012 budget request and to take questions from employees. Photo Credit: (NASA/Bill Ingalls)

  16. Scan path entropy and arrow plots: capturing scanning behavior of multiple observers

    PubMed Central

    Hooge, Ignace; Camps, Guido

    2013-01-01

    Designers of visual communication material want their material to attract and retain attention. In marketing research, heat maps, dwell time, and time to AOI first hit are often used as evaluation parameters. Here we present two additional measures (1) “scan path entropy” to quantify gaze guidance and (2) the “arrow plot” to visualize the average scan path. Both are based on string representations of scan paths. The latter also incorporates transition matrices and time required for 50% of the observers to first hit AOIs (T50). The new measures were tested in an eye tracking study (48 observers, 39 advertisements). Scan path entropy is a sensible measure for gaze guidance and the new visualization method reveals aspects of the average scan path and gives a better indication in what order global scanning takes place. PMID:24399993

  17. Nonsynchronous updating in the multiverse of cellular automata

    NASA Astrophysics Data System (ADS)

    Reia, Sandro M.; Kinouchi, Osame

    2015-04-01

    In this paper we study updating effects on cellular automata rule space. We consider a subset of 6144 order-3 automata from the space of 262144 bidimensional outer-totalistic rules. We compare synchronous to asynchronous and sequential updatings. Focusing on two automata, we discuss how update changes destroy typical structures of these rules. Besides, we show that the first-order phase transition in the multiverse of synchronous cellular automata, revealed with the use of a recently introduced control parameter, seems to be robust not only to changes in update schema but also to different initial densities.

  18. Nonsynchronous updating in the multiverse of cellular automata.

    PubMed

    Reia, Sandro M; Kinouchi, Osame

    2015-04-01

    In this paper we study updating effects on cellular automata rule space. We consider a subset of 6144 order-3 automata from the space of 262144 bidimensional outer-totalistic rules. We compare synchronous to asynchronous and sequential updatings. Focusing on two automata, we discuss how update changes destroy typical structures of these rules. Besides, we show that the first-order phase transition in the multiverse of synchronous cellular automata, revealed with the use of a recently introduced control parameter, seems to be robust not only to changes in update schema but also to different initial densities.

  19. NASA Update for Unidata Stratcomm

    NASA Technical Reports Server (NTRS)

    Lynnes, Chris

    2017-01-01

    The NASA representative to the Unidata Strategic Committee presented a semiannual update on NASAs work with and use of Unidata technologies. The talk updated Unidata on the program of cloud computing prototypes underway for the Earth Observing System Data and Information System (EOSDIS). Also discussed was a trade study on the use of the Open source Project for a Network Data Access Protocol (OPeNDAP) with Web Object Storage in the cloud.

  20. Apparatus for controlling the scan width of a scanning laser beam

    DOEpatents

    Johnson, G.W.

    1996-10-22

    Swept-wavelength lasers are often used in absorption spectroscopy applications. In experiments where high accuracy is required, it is desirable to continuously monitor and control the range of wavelengths scanned (the scan width). A system has been demonstrated whereby the scan width of a swept ring-dye laser, or semiconductor diode laser, can be measured and controlled in real-time with a resolution better than 0.1%. Scan linearity, or conformity to a nonlinear scan waveform, can be measured and controlled. The system of the invention consists of a Fabry-Perot interferometer, three CAMAC interface modules, and a microcomputer running a simple analysis and proportional-integral control algorithm. With additional modules, multiple lasers can be simultaneously controlled. The invention also includes an embodiment implemented on an ordinary PC with a multifunction plug-in board. 8 figs.

  1. Magnetic particle-scanning for ultrasensitive immunodetection on-chip.

    PubMed

    Cornaglia, Matteo; Trouillon, Raphaël; Tekin, H Cumhur; Lehnert, Thomas; Gijs, Martin A M

    2014-08-19

    We describe the concept of magnetic particle-scanning for on-chip detection of biomolecules: a magnetic particle, carrying a low number of antigens (Ag's) (down to a single molecule), is transported by hydrodynamic forces and is subjected to successive stochastic reorientations in an engineered magnetic energy landscape. The latter consists of a pattern of substrate-bound small magnetic particles that are functionalized with antibodies (Ab's). Subsequationuent counting of the captured Ag-carrying particles provides the detection signal. The magnetic particle-scanning principle is investigated in a custom-built magneto-microfluidic chip and theoretically described by a random walk-based model, in which the trajectory of the contact point between an Ag-carrying particle and the small magnetic particle pattern is described by stochastic moves over the surface of the mobile particle, until this point coincides with the position of an Ag, resulting in the binding of the particle. This model explains the particular behavior of previously reported experimental dose-response curves obtained for two different ligand-receptor systems (biotin/streptavidin and TNF-α) over a wide range of concentrations. Our model shows that magnetic particle-scanning results in a very high probability of immunocomplex formation for very low Ag concentrations, leading to an extremely low limit of detection, down to the single molecule-per-particle level. When compared to other types of magnetic particle-based surface coverage assays, our strategy was found to offer a wider dynamic range (>8 orders of magnitude), as the system does not saturate for concentrations as high as 10(11) Ag molecules in a 5 μL drop. Furthermore, by emphasizing the importance of maximizing the encounter probability between the Ag and the Ab to improve sensitivity, our model also contributes to explaining the behavior of other particle-based heterogeneous immunoassays.

  2. Red Hill Updates

    EPA Pesticide Factsheets

    This and other periodic updates are intended to keep the public informed on major progress being made to protect public health and the environment at the Red Hill Underground Fuel Storage Facility in Hawaii.

  3. Neuropeptide S receptor ligands: a patent review (2005-2016).

    PubMed

    Ruzza, Chiara; Calò, Girolamo; Di Maro, Salvatore; Pacifico, Salvatore; Trapella, Claudio; Salvadori, Severo; Preti, Delia; Guerrini, Remo

    2017-03-01

    Neuropeptide S (NPS) is a 20-residue peptide and endogenous ligand of the NPS receptor (NPSR). This receptor was a formerly orphan GPCR whose activation increases calcium and cyclic adenosine monophosphate levels. The NPS/NPSR system is expressed in several brain regions where it controls important biological functions including locomotor activity, arousal and sleep, anxiety, food intake, memory, pain, and drug addiction. Areas covered: This review furnishes an updated overview of the patent literature covering NPSR ligands since 2005, when the first example of an NPSR antagonist was disclosed. Expert opinion: Several potent NPSR antagonists are available as valuable pharmacological tools despite showing suboptimal pharmacokinetic properties in vivo. The optimization of these ligands is needed to speed up their potential clinical advancement as pharmaceuticals to treat drug addiction. In order to support the design of novel NPSR antagonists, we performed a ligand-based conformational analysis recognizing some structural requirements for NPSR antagonism. The identification of small-molecule NPSR agonists now represents an unmet challenge to be addressed. These molecules will allow investigation of the beneficial effects of selective NPSR activation in a large panel of psychiatric disorders and to foresee their therapeutic potential as anxiolytics, nootropics, and analgesics.

  4. Immersion ultrasonography: simultaneous A-scan and B-scan.

    PubMed

    Coleman, D J; Dallow, R L; Smith, M E

    1979-01-01

    In eyes with opaque media, ophthalmic ultrasound provides a unique source of information that can dramatically affect the course of patient management. In addition, when an ocular abnormality can be visualized, ultrasonography provides information that supplements and complements other diagnostic testing. It provides documentation and differentiation of abnormal states, such as vitreous hemorrhage and intraocular tumor, as well as differentiation of orbital tumors from inflammatory causes of exophthalmos. Additional capabilities of ultrasound are biometric determinations for calculation of intraocular lens implant powers and drug-effectiveness studies. Maximal information is derived from ultrasonography when A-scan and B-scan techniques are employed simultaneously. Flexibility of electronics, variable-frequency transducers, and the use of several different manual scanning patterns aid in detection and interpretation of results. The immersion system of ultrasonography provides these features optimally.

  5. Update '98.

    ERIC Educational Resources Information Center

    Mock, Karen R.

    1998-01-01

    Updates cases and issues previously discussed in this regular column on human rights in Canada, including racism and anti-Semitism, laws on hate crimes, hate sites on the World Wide Web, the use of the "free speech" defense by hate groups, and legal challenges to antiracist groups by individuals criticized by them. (DSK)

  6. Calcitonin and Amylin Receptor Peptide Interaction Mechanisms

    PubMed Central

    Lee, Sang-Min; Hay, Debbie L.; Pioszak, Augen A.

    2016-01-01

    Receptor activity-modifying proteins (RAMP1–3) determine the selectivity of the class B G protein-coupled calcitonin receptor (CTR) and the CTR-like receptor (CLR) for calcitonin (CT), amylin (Amy), calcitonin gene-related peptide (CGRP), and adrenomedullin (AM) peptides. RAMP1/2 alter CLR selectivity for CGRP/AM in part by RAMP1 Trp-84 or RAMP2 Glu-101 contacting the distinct CGRP/AM C-terminal residues. It is unclear whether RAMPs use a similar mechanism to modulate CTR affinity for CT and Amy, analogs of which are therapeutics for bone disorders and diabetes, respectively. Here, we reproduced the peptide selectivity of intact CTR, AMY1 (CTR·RAMP1), and AMY2 (CTR·RAMP2) receptors using purified CTR extracellular domain (ECD) and tethered RAMP1- and RAMP2-CTR ECD fusion proteins and antagonist peptides. All three proteins bound salmon calcitonin (sCT). Tethering RAMPs to CTR enhanced binding of rAmy, CGRP, and the AMY antagonist AC413. Peptide alanine-scanning mutagenesis and modeling of receptor-bound sCT and AC413 supported a shared non-helical CGRP-like conformation for their TN(T/V)G motif prior to the C terminus. After this motif, the peptides diverged; the sCT C-terminal Pro was crucial for receptor binding, whereas the AC413/rAmy C-terminal Tyr had little or no influence on binding. Accordingly, mutant RAMP1 W84A- and RAMP2 E101A-CTR ECD retained AC413/rAmy binding. ECD binding and cell-based signaling assays with antagonist sCT/AC413/rAmy variants with C-terminal residue swaps indicated that the C-terminal sCT/rAmy residue identity affects affinity more than selectivity. rAmy(8–37) Y37P exhibited enhanced antagonism of AMY1 while retaining selectivity. These results reveal unexpected differences in how RAMPs determine CTR and CLR peptide selectivity and support the hypothesis that RAMPs allosterically modulate CTR peptide affinity. PMID:26895962

  7. Chitin-induced and CHITIN ELICITOR RECEPTOR KINASE1 (CERK1) phosphorylation-dependent endocytosis of Arabidopsis thaliana LYSIN MOTIF-CONTAINING RECEPTOR-LIKE KINASE5 (LYK5).

    PubMed

    Erwig, Jan; Ghareeb, Hassan; Kopischke, Michaela; Hacke, Ronja; Matei, Alexandra; Petutschnig, Elena; Lipka, Volker

    2017-07-01

    To detect potential pathogens, plants perceive the fungal polysaccharide chitin through receptor complexes containing lysin motif receptor-like kinases (LysM-RLKs). To investigate the ligand-induced spatial dynamics of chitin receptor components, we studied the subcellular behaviour of two Arabidopsis thaliana LysM-RLKs involved in chitin signalling, CHITIN ELICITOR RECEPTOR KINASE1 (CERK1) and LYSIN MOTIF-CONTAINING RECEPTOR-LIKE KINASE5. We performed standard and quantitative confocal laser scanning microscopy on stably transformed A. thaliana plants expressing fluorescently tagged CERK1 and LYK5 from their native promoters. Microscopy approaches were complemented by biochemical analyses in plants and in vitro. Both CERK1 and LYK5 localized to the plasma membrane and showed constitutive endomembrane trafficking. After chitin treatment, however, CERK1 remained at the plasma membrane while LYK5 relocalized into mobile intracellular vesicles. Detailed analyses revealed that chitin perception transiently induced the internalization of LYK5 into late endocytic compartments. Plants that lacked CERK1 or expressed an enzymatically inactive CERK1 variant did not exhibit chitin-induced endocytosis of LYK5. CERK1 could phosphorylate LYK5 in vitro and chitin treatment induced CERK1-dependent phosphorylation of LYK5 in planta. Our results suggest that chitin-induced phosphorylation by CERK1 triggers LYK5 internalization. Thus, our work identifies phosphorylation as a key regulatory step in endocytosis of plant RLKs and also provides evidence for receptor complex dissociation after ligand perception. © 2017 The Authors. New Phytologist © 2017 New Phytologist Trust.

  8. Factors influencing infants’ ability to update object representations in memory

    PubMed Central

    Moher, Mariko; Feigenson, Lisa

    2013-01-01

    Remembering persisting objects over occlusion is critical to representing a stable environment. Infants remember hidden objects at multiple locations and can update their representation of a hidden array when an object is added or subtracted. However, the factors influencing these updating abilities have received little systematic exploration. Here we examined the flexibility of infants’ ability to update object representations. We tested 11-month-olds in a looking-time task in which objects were added to or subtracted from two hidden arrays. Across five experiments, infants successfully updated their representations of hidden arrays when the updating occurred successively at one array before beginning at the other. But when updating required alternating between two arrays, infants failed. However, simply connecting the two arrays with a thin strip of foam-core led infants to succeed. Our results suggest that infants’ construal of an event strongly affects their ability to update memory representations of hidden objects. When construing an event as containing multiple updates to the same array, infants succeed, but when construing the event as requiring the revisiting and updating of previously attended arrays, infants fail. PMID:24049245

  9. Part C Updates: 9th Edition

    ERIC Educational Resources Information Center

    Danaher, Joan; Goode, Sue; Lazara, Alex

    2007-01-01

    "Part C Updates" is a compilation of information on various aspects of the Early Intervention Program for Infants and Toddlers with Disabilities (Part C) of the Individuals with Disabilities Education Act (IDEA). This is the ninth volume in a series of compilations, which included two editions of Part H Updates, the former name of the…

  10. Federal Education Update, December 2004. Commission Update 04-17.

    ERIC Educational Resources Information Center

    California Postsecondary Education Commission, 2004

    2004-01-01

    This update presents some of the major issues affecting education occurring at the national level. These include: Higher Education Act Extended for One Year; New Law Increases Loan Forgiveness for Teachers; Domestic Appropriations Measures Completed; Change in Federal Student Aid Rules; Bush Advisor Nominated To Be Education Secretary In Second…

  11. UPDATE: Applications of Research in Music Education. UPDATE Yearbook

    ERIC Educational Resources Information Center

    Rowman & Littlefield Education, 2005

    2005-01-01

    The Fall 2004 and Spring 2005 issues of "UPDATE: Applications of Research in Music Education," in one print volume, presents hard facts and statistical data in a style that can be easily understood and appreciated by music researchers, teachers, graduates, and undergraduates alike. Includes advice to first-year music teachers, instrument…

  12. Opiate receptors in idiopathic generalised epilepsy measured with [11C]diprenorphine and positron emission tomography.

    PubMed

    Prevett, M C; Cunningham, V J; Brooks, D J; Fish, D R; Duncan, J S

    1994-09-01

    The neurochemical basis of absence seizures is uncertain. A previous PET study has provided evidence for release of endogenous opioids from cerebral cortex at the time of absence seizures, but it is has not yet been established whether there is an abnormality of opiate receptor numbers interictally. In the present study, the non-specific opiate receptor ligand, [11C]diprenorphine, was used to measure cerebral opiate receptors interictally in patients with childhood and juvenile absence epilepsy. Eight patients and eight normal controls had a single scan after a high specific activity injection of [11C]diprenorphine. The cerebral volume of distribution (Vd) of [11C]diprenorphine relative to plasma was calculated on a pixel-by-pixel basis. There were no significant differences in [11C]diprenorphine Vd between patients and control subjects in either cortex or thalamus, structures thought to be involved in the pathogenesis of absence seizures. The results suggest that there is no overall abnormality of opioid receptors in patients with childhood and juvenile absence epilepsy. Studies with specific ligands may provide information about the different receptor subtypes.

  13. Agent Communication for Dynamic Belief Update

    NASA Astrophysics Data System (ADS)

    Kobayashi, Mikito; Tojo, Satoshi

    Thus far, various formalizations of rational / logical agent model have been proposed. In this paper, we include the notion of communication channel and belief modality into update logic, and introduce Belief Update Logic (BUL). First, we discuss that how we can reformalize the inform action of FIPA-ACL into communication channel, which represents a connection between agents. Thus, our agents can send a message only when they believe, and also there actually is, a channel between him / her and a receiver. Then, we present a static belief logic (BL) and show its soundness and completeness. Next, we develop the logic to BUL, which can update Kripke model by the inform action; in which we show that in the updated model the belief operator also satisfies K45. Thereafter, we show that every sentence in BUL can be translated into BL; thus, we can contend that BUL is also sound and complete. Furthermore, we discuss the features of CUL, including the case of inconsistent information, as well as channel transmission. Finally, we summarize our contribution and discuss some future issues.

  14. Update on the urotensinergic system: new trends in receptor localization, activation, and drug design

    PubMed Central

    Chatenet, David; Nguyen, Thi-Tuyet M.; Létourneau, Myriam; Fournier, Alain

    2012-01-01

    The urotensinergic system plays central roles in the physiological regulation of major mammalian organ systems, including the cardiovascular system. As a matter of fact, this system has been linked to numerous pathophysiological states including atherosclerosis, heart failure, hypertension, diabetes as well as psychological, and neurological disorders. The delineation of the (patho)physiological roles of the urotensinergic system has been hampered by the absence of potent and selective antagonists for the urotensin II-receptor (UT). Thus, a more precise definition of the molecular functioning of the urotensinergic system, in normal conditions as well as in a pathological state is still critically needed. The recent discovery of nuclear UT within cardiomyocytes has highlighted the cellular complexity of this system and suggested that UT-associated biological responses are not only initiated at the cell surface but may result from the integration of extracellular and intracellular signaling pathways. Thus, such nuclear-localized receptors, regulating distinct signaling pathways, may represent new therapeutic targets. With the recent observation that urotensin II (UII) and urotensin II-related peptide (URP) exert different biological effects and the postulate that they could also have distinct pathophysiological roles in hypertension, it appears crucial to reassess the recognition process involving UII and URP with UT, and to push forward the development of new analogs of the UT system aimed at discriminating UII- and URP-mediated biological activities. The recent development of such compounds, i.e. urocontrin A and rUII(1–7), is certainly useful to decipher the specific roles of UII and URP in vitro and in vivo. Altogether, these studies, which provide important information regarding the pharmacology of the urotensinergic system and the conformational requirements for binding and activation, will ultimately lead to the development of potent and selective drugs

  15. International Union of Basic and Clinical Pharmacology. LXXXVIII. G Protein-Coupled Receptor List: Recommendations for New Pairings with Cognate Ligands

    PubMed Central

    Alexander, Stephen P. H.; Sharman, Joanna L.; Pawson, Adam J.; Benson, Helen E.; Monaghan, Amy E.; Liew, Wen Chiy; Mpamhanga, Chidochangu P.; Bonner, Tom I.; Neubig, Richard R.; Pin, Jean Philippe; Spedding, Michael; Harmar, Anthony J.

    2013-01-01

    In 2005, the International Union of Basic and Clinical Pharmacology Committee on Receptor Nomenclature and Drug Classification (NC-IUPHAR) published a catalog of all of the human gene sequences known or predicted to encode G protein-coupled receptors (GPCRs), excluding sensory receptors. This review updates the list of orphan GPCRs and describes the criteria used by NC-IUPHAR to recommend the pairing of an orphan receptor with its cognate ligand(s). The following recommendations are made for new receptor names based on 11 pairings for class A GPCRs: hydroxycarboxylic acid receptors [HCA1 (GPR81) with lactate, HCA2 (GPR109A) with 3-hydroxybutyric acid, HCA3 (GPR109B) with 3-hydroxyoctanoic acid]; lysophosphatidic acid receptors [LPA4 (GPR23), LPA5 (GPR92), LPA6 (P2Y5)]; free fatty acid receptors [FFA4 (GPR120) with omega-3 fatty acids]; chemerin receptor (CMKLR1; ChemR23) with chemerin; CXCR7 (CMKOR1) with chemokines CXCL12 (SDF-1) and CXCL11 (ITAC); succinate receptor (SUCNR1) with succinate; and oxoglutarate receptor [OXGR1 with 2-oxoglutarate]. Pairings are highlighted for an additional 30 receptors in class A where further input is needed from the scientific community to validate these findings. Fifty-seven human class A receptors (excluding pseudogenes) are still considered orphans; information has been provided where there is a significant phenotype in genetically modified animals. In class B, six pairings have been reported by a single publication, with 28 (excluding pseudogenes) still classified as orphans. Seven orphan receptors remain in class C, with one pairing described by a single paper. The objective is to stimulate research into confirming pairings of orphan receptors where there is currently limited information and to identify cognate ligands for the remaining GPCRs. Further information can be found on the IUPHAR Database website (http://www.iuphar-db.org). PMID:23686350

  16. Involvement of substance P and the NK-1 receptor in human pathology.

    PubMed

    Muñoz, Miguel; Coveñas, Rafael

    2014-07-01

    The peptide substance P (SP) shows a widespread distribution in both the central and peripheral nervous systems, but it is also present in cells not belonging to the nervous system (immune cells, liver, lung, placenta, etc.). SP is located in all body fluids, such as blood, cerebrospinal fluid, breast milk, etc. i.e. it is ubiquitous in human body. After binding to the neurokinin-1 (NK-1) receptor, SP regulates many pathophysiological functions in the central nervous system, such as emotional behavior, stress, depression, anxiety, emesis, vomiting, migraine, alcohol addiction, seizures and neurodegeneration. SP has been also implicated in pain, inflammation, hepatitis, hepatotoxicity, cholestasis, pruritus, myocarditis, bronchiolitis, abortus, bacteria and viral infection (e.g., HIV infection) and it plays an important role in cancer (e.g., tumor cell proliferation, antiapoptotic effects in tumor cells, angiogenesis, migration of tumor cells for invasion, infiltration and metastasis). This means that the SP/NK-1 receptor system is involved in the molecular bases of many human pathologies. Thus, knowledge of this system is the key for a better understanding and hence a better management of many human diseases. In this review, we update the involvement of the SP/NK-1 receptor system in the physiopathology of the above-mentioned pathologies and we suggest valuable future therapeutic interventions involving the use of NK-1 receptor antagonists, particularly in the treatment of emesis, depression, cancer, neural degeneration, inflammatory bowel disease, viral infection and pruritus, in which that system is upregulated.

  17. Kennedy Space Center Director Update

    NASA Image and Video Library

    2014-03-06

    CAPE CANAVERAL, Fla. - Community leaders, business executives, educators, and state and local government leaders were updated on NASA Kennedy Space Center programs and accomplishments during Center Director Bob Cabana’s Center Director Update at the Debus Center at the Kennedy Space Center Visitor Complex in Florida. From left, Scott Thurston, Kennedy deputy of the spacecraft office of the Commercial Crew Program, talks with Scott Colloredo, director of the Center Planning and Development Directorate. Attendees talked with Cabana and other senior Kennedy managers and visited displays featuring updates on Kennedy programs and projects, including International Space Station, Commercial Crew, Ground System Development and Operations, Launch Services, Center Planning and Development, Technology, KSC Swamp Works and NASA Education. The morning concluded with a tour of the new Space Shuttle Atlantis exhibit at the visitor complex. For more information, visit http://www.nasa.gov/kennedy. Photo credit: NASA/Daniel Casper

  18. Kennedy Space Center Director Update

    NASA Image and Video Library

    2014-03-06

    CAPE CANAVERAL, Fla. - Community leaders, business executives, educators, and state and local government leaders were updated on NASA Kennedy Space Center programs and accomplishments during Center Director Bob Cabana’s Center Director Update at the Debus Center at the Kennedy Space Center Visitor Complex in Florida. Attendees talk with Trey Carlson, Kennedy Master Planner, at the Center Planning and Development Directorate, or CPDD, display. In the background is Mario Busacca, chief of CPDD’s Spaceport Planning Office. Attendees talked with Cabana and other senior Kennedy managers and visited displays featuring updates on Kennedy programs and projects, including International Space Station, Commercial Crew, Ground System Development and Operations, Launch Services, Center Planning and Development, Technology, KSC Swamp Works and NASA Education. The morning concluded with a tour of the new Space Shuttle Atlantis exhibit at the visitor complex. For more information, visit http://www.nasa.gov/kennedy. Photo credit: NASA/Daniel Casper

  19. Histamine H3 receptor density is negatively correlated with neural activity related to working memory in humans.

    PubMed

    Ito, Takehito; Kimura, Yasuyuki; Seki, Chie; Ichise, Masanori; Yokokawa, Keita; Kawamura, Kazunori; Takahashi, Hidehiko; Higuchi, Makoto; Zhang, Ming-Rong; Suhara, Tetsuya; Yamada, Makiko

    2018-06-14

    The histamine H 3 receptor is regarded as a drug target for cognitive impairments in psychiatric disorders. H 3 receptors are expressed in neocortical areas, including the prefrontal cortex, the key region of cognitive functions such as working memory. However, the role of prefrontal H 3 receptors in working memory has not yet been clarified. Therefore, using functional magnetic resonance imaging (fMRI) and positron emission tomography (PET) techniques, we aimed to investigate the association between the neural activity of working memory and the density of H 3 receptors in the prefrontal cortex. Ten healthy volunteers underwent both fMRI and PET scans. The N-back task was used to assess the neural activities related to working memory. H 3 receptor density was measured with the selective PET radioligand [ 11 C] TASP457. The neural activity of the right dorsolateral prefrontal cortex during the performance of the N-back task was negatively correlated with the density of H 3 receptors in this region. Higher neural activity of working memory was associated with lower H 3 receptor density in the right dorsolateral prefrontal cortex. This finding elucidates the role of H 3 receptors in working memory and indicates the potential of H 3 receptors as a therapeutic target for the cognitive impairments associated with neuropsychiatric disorders.

  20. 49 CFR 1002.3 - Updating user fees.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... Services, 1 I.C.C.2d 60 (1984) or subsequent cost studies. The base period for measuring changes shall be... material in the Federal Register. (e) Rounding of updated fees. Updated fees shall be rounded in the...

  1. 49 CFR 1002.3 - Updating user fees.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... Services, 1 I.C.C.2d 60 (1984) or subsequent cost studies. The base period for measuring changes shall be... material in the Federal Register. (e) Rounding of updated fees. Updated fees shall be rounded in the...

  2. 49 CFR 1002.3 - Updating user fees.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... Services, 1 I.C.C.2d 60 (1984) or subsequent cost studies. The base period for measuring changes shall be... material in the Federal Register. (e) Rounding of updated fees. Updated fees shall be rounded in the...

  3. 1 CFR 8.3 - Periodic updating.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 1 General Provisions 1 2011-01-01 2011-01-01 false Periodic updating. 8.3 Section 8.3 General... the intent and purpose of the Administrative Committee as stated in § 8.1. (b) Staggered publication... before the “As of” date. Thus, each title updated as of July 1 each year will reflect all amendatory...

  4. 1 CFR 8.3 - Periodic updating.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 1 General Provisions 1 2010-01-01 2010-01-01 false Periodic updating. 8.3 Section 8.3 General... the intent and purpose of the Administrative Committee as stated in § 8.1. (b) Staggered publication... before the “As of” date. Thus, each title updated as of July 1 each year will reflect all amendatory...

  5. 34 CFR 668.55 - Updating information.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 34 Education 3 2010-07-01 2010-07-01 false Updating information. 668.55 Section 668.55 Education... Information § 668.55 Updating information. (a)(1) Unless the provisions of paragraph (a)(2) or (a)(3) of this... applicant to verify the information contained in his or her application for assistance in an award year if...

  6. 1 CFR 8.3 - Periodic updating.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 1 General Provisions 1 2012-01-01 2012-01-01 false Periodic updating. 8.3 Section 8.3 General... the intent and purpose of the Administrative Committee as stated in § 8.1. (b) Staggered publication... before the “As of” date. Thus, each title updated as of July 1 each year will reflect all amendatory...

  7. 1 CFR 8.3 - Periodic updating.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 1 General Provisions 1 2014-01-01 2012-01-01 true Periodic updating. 8.3 Section 8.3 General... the intent and purpose of the Administrative Committee as stated in § 8.1. (b) Staggered publication... before the “As of” date. Thus, each title updated as of July 1 each year will reflect all amendatory...

  8. 1 CFR 8.3 - Periodic updating.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 1 General Provisions 1 2013-01-01 2012-01-01 true Periodic updating. 8.3 Section 8.3 General... the intent and purpose of the Administrative Committee as stated in § 8.1. (b) Staggered publication... before the “As of” date. Thus, each title updated as of July 1 each year will reflect all amendatory...

  9. Utilizing Flight Data to Update Aeroelastic Stability Estimates

    NASA Technical Reports Server (NTRS)

    Lind, Rick; Brenner, Marty

    1997-01-01

    Stability analysis of high performance aircraft must account for errors in the system model. A method for computing flutter margins that incorporates flight data has been developed using robust stability theory. This paper considers applying this method to update flutter margins during a post-flight or on-line analysis. Areas of modeling uncertainty that arise when using flight data with this method are investigated. The amount of conservatism in the resulting flutter margins depends on the flight data sets used to update the model. Post-flight updates of flutter margins for an F/A-18 are presented along with a simulation of on-line updates during a flight test.

  10. Rapid-scan EPR imaging.

    PubMed

    Eaton, Sandra S; Shi, Yilin; Woodcock, Lukas; Buchanan, Laura A; McPeak, Joseph; Quine, Richard W; Rinard, George A; Epel, Boris; Halpern, Howard J; Eaton, Gareth R

    2017-07-01

    In rapid-scan EPR the magnetic field or frequency is repeatedly scanned through the spectrum at rates that are much faster than in conventional continuous wave EPR. The signal is directly-detected with a mixer at the source frequency. Rapid-scan EPR is particularly advantageous when the scan rate through resonance is fast relative to electron spin relaxation rates. In such scans, there may be oscillations on the trailing edge of the spectrum. These oscillations can be removed by mathematical deconvolution to recover the slow-scan absorption spectrum. In cases of inhomogeneous broadening, the oscillations may interfere destructively to the extent that they are not visible. The deconvolution can be used even when it is not required, so spectra can be obtained in which some portions of the spectrum are in the rapid-scan regime and some are not. The technology developed for rapid-scan EPR can be applied generally so long as spectra are obtained in the linear response region. The detection of the full spectrum in each scan, the ability to use higher microwave power without saturation, and the noise filtering inherent in coherent averaging results in substantial improvement in signal-to-noise relative to conventional continuous wave spectroscopy, which is particularly advantageous for low-frequency EPR imaging. This overview describes the principles of rapid-scan EPR and the hardware used to generate the spectra. Examples are provided of its application to imaging of nitroxide radicals, diradicals, and spin-trapped radicals at a Larmor frequency of ca. 250MHz. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Cervical spine CT scan

    MedlinePlus

    ... cervical spine; Computed tomography scan of cervical spine; CT scan of cervical spine; Neck CT scan ... table that slides into the center of the CT scanner. Once you are inside the scanner, the ...

  12. Control of interference during working memory updating.

    PubMed

    Szmalec, Arnaud; Verbruggen, Frederick; Vandierendonck, André; Kemps, Eva

    2011-02-01

    The current study examined the nature of the processes underlying working memory updating. In 4 experiments using the n-back paradigm, the authors demonstrate that continuous updating of items in working memory prevents strong binding of those items to their contexts in working memory, and hence leads to an increased susceptibility to proactive interference. Results of Experiments 1 and 2 show that this interference reflects a competition between a process that reveals the degree of familiarity of an item and a context-sensitive recollection process that depends on the strength of bindings in working memory. Experiment 3 further clarifies the origins of interference during updating by demonstrating that even items that are semantically related to the updated working memory contents but that have not been maintained in working memory before cause proactive interference. Finally, the results of Experiment 4 indicate that the occurrence of interference leads to top-down behavioral adjustments that prioritize recollection over familiarity assessment. The implications of these findings for the construct validity of the n-back task, for the control processes involved in working memory updating, and for the concept of executive control more generally are discussed. (c) 2010 APA, all rights reserved.

  13. NASA Update

    NASA Image and Video Library

    2011-02-15

    NASA Administrator Charles F. Bolden Jr., and Deputy Administrator Lori Garver deliver a NASA Update on, Tuesday, Feb. 15, 2011, at NASA Headquarters in Washington. Bolden, NASA's 12th Administrator and Garver took the time discuss the agency’s fiscal year 2012 budget request and to take questions from employees. Photo Credit: (NASA/Bill Ingalls)

  14. NASA Update

    NASA Image and Video Library

    2011-02-15

    NASA Deputy Administrator Lori Garver listens as NASA Administrator Charles Bolden answers a question during a NASA Update on Tuesday, Feb. 15, 2011, at NASA Headquarters in Washington. Bolden and Garver took the time discuss the agency’s fiscal year 2012 budget request and to take questions from employees. Photo Credit: (NASA/Bill Ingalls)

  15. Alternative Fuels Data Center: Status Update: Clarification of Ethanol

    Science.gov Websites

    Center: Status Update: Clarification of Ethanol Certification Limits for Legacy Equipment (December 2008 ) on Facebook Tweet about Alternative Fuels Data Center: Status Update: Clarification of Ethanol : Status Update: Clarification of Ethanol Certification Limits for Legacy Equipment (December 2008) on

  16. Scanning two-photon microscopy with upconverting lanthanide nanoparticles via Richardson-Lucy deconvolution.

    PubMed

    Gainer, Christian F; Utzinger, Urs; Romanowski, Marek

    2012-07-01

    The use of upconverting lanthanide nanoparticles in fast-scanning microscopy is hindered by a long luminescence decay time, which greatly blurs images acquired in a nondescanned mode. We demonstrate herein an image processing method based on Richardson-Lucy deconvolution that mitigates the detrimental effects of their luminescence lifetime. This technique generates images with lateral resolution on par with the system's performance, ∼1.2  μm, while maintaining an axial resolution of 5 μm or better at a scan rate comparable with traditional two-photon microscopy. Remarkably, this can be accomplished with near infrared excitation power densities of 850 W/cm(2), several orders of magnitude below those used in two-photon imaging with molecular fluorophores. By way of illustration, we introduce the use of lipids to coat and functionalize these nanoparticles, rendering them water dispersible and readily conjugated to biologically relevant ligands, in this case epidermal growth factor receptor antibody. This deconvolution technique combined with the functionalized nanoparticles will enable three-dimensional functional tissue imaging at exceptionally low excitation power densities.

  17. Evolutionary Analysis of Functional Divergence among Chemokine Receptors, Decoy Receptors, and Viral Receptors

    PubMed Central

    Daiyasu, Hiromi; Nemoto, Wataru; Toh, Hiroyuki

    2012-01-01

    Chemokine receptors (CKRs) function in the inflammatory response and in vertebrate homeostasis. Decoy and viral receptors are two types of CKR homologs with modified functions from those of the typical CKRs. The decoy receptors are able to bind ligands without signaling. On the other hand, the viral receptors show constitutive signaling without ligands. We examined the sites related to the functional difference. At first, the decoy and viral receptors were each classified into five groups, based on the molecular phylogenetic analysis. A multiple amino acid sequence alignment between each group and the CKRs was then constructed. The difference in the amino acid composition between the group and the CKRs was evaluated as the Kullback–Leibler (KL) information value at each alignment site. The KL information value is considered to reflect the difference in the functional constraints at the site. The sites with the top 5% of KL information values were selected and mapped on the structure of a CKR. The comparisons with decoy receptor groups revealed that the detected sites were biased on the intracellular side. In contrast, the sites detected from the comparisons with viral receptor groups were found on both the extracellular and intracellular sides. More sites were found in the ligand binding pocket in the analyses of the viral receptor groups, as compared to the decoy receptor groups. Some of the detected sites were located in the GPCR motifs. For example, the DRY motif of the decoy receptors was often degraded, although the motif of the viral receptors was basically conserved. The observations for the viral receptor groups suggested that the constraints in the pocket region are loose and that the sites on the intracellular side are different from those for the decoy receptors, which may be related to the constitutive signaling activity of the viral receptors. PMID:22855685

  18. Evolutionary Analysis of Functional Divergence among Chemokine Receptors, Decoy Receptors, and Viral Receptors.

    PubMed

    Daiyasu, Hiromi; Nemoto, Wataru; Toh, Hiroyuki

    2012-01-01

    Chemokine receptors (CKRs) function in the inflammatory response and in vertebrate homeostasis. Decoy and viral receptors are two types of CKR homologs with modified functions from those of the typical CKRs. The decoy receptors are able to bind ligands without signaling. On the other hand, the viral receptors show constitutive signaling without ligands. We examined the sites related to the functional difference. At first, the decoy and viral receptors were each classified into five groups, based on the molecular phylogenetic analysis. A multiple amino acid sequence alignment between each group and the CKRs was then constructed. The difference in the amino acid composition between the group and the CKRs was evaluated as the Kullback-Leibler (KL) information value at each alignment site. The KL information value is considered to reflect the difference in the functional constraints at the site. The sites with the top 5% of KL information values were selected and mapped on the structure of a CKR. The comparisons with decoy receptor groups revealed that the detected sites were biased on the intracellular side. In contrast, the sites detected from the comparisons with viral receptor groups were found on both the extracellular and intracellular sides. More sites were found in the ligand binding pocket in the analyses of the viral receptor groups, as compared to the decoy receptor groups. Some of the detected sites were located in the GPCR motifs. For example, the DRY motif of the decoy receptors was often degraded, although the motif of the viral receptors was basically conserved. The observations for the viral receptor groups suggested that the constraints in the pocket region are loose and that the sites on the intracellular side are different from those for the decoy receptors, which may be related to the constitutive signaling activity of the viral receptors.

  19. Numerical model updating technique for structures using firefly algorithm

    NASA Astrophysics Data System (ADS)

    Sai Kubair, K.; Mohan, S. C.

    2018-03-01

    Numerical model updating is a technique used for updating the existing experimental models for any structures related to civil, mechanical, automobiles, marine, aerospace engineering, etc. The basic concept behind this technique is updating the numerical models to closely match with experimental data obtained from real or prototype test structures. The present work involves the development of numerical model using MATLAB as a computational tool and with mathematical equations that define the experimental model. Firefly algorithm is used as an optimization tool in this study. In this updating process a response parameter of the structure has to be chosen, which helps to correlate the numerical model developed with the experimental results obtained. The variables for the updating can be either material or geometrical properties of the model or both. In this study, to verify the proposed technique, a cantilever beam is analyzed for its tip deflection and a space frame has been analyzed for its natural frequencies. Both the models are updated with their respective response values obtained from experimental results. The numerical results after updating show that there is a close relationship that can be brought between the experimental and the numerical models.

  20. Infrared zone-scanning system.

    PubMed

    Belousov, Aleksandr; Popov, Gennady

    2006-03-20

    Challenges encountered in designing an infrared viewing optical system that uses a small linear detector array based on a zone-scanning approach are discussed. Scanning is performed by a rotating refractive polygon prism with tilted facets, which, along with high-speed line scanning, makes the scanning gear as simple as possible. A method of calculation of a practical optical system to compensate for aberrations during prism rotation is described.

  1. Identification of key residues involved in adrenomedullin binding to the AM1 receptor

    PubMed Central

    Watkins, HA; Au, M; Bobby, R; Archbold, JK; Abdul-Manan, N; Moore, JM; Middleditch, MJ; Williams, GM; Brimble, MA; Dingley, AJ; Hay, DL

    2013-01-01

    Background and Purpose Adrenomedullin (AM) is a peptide hormone whose receptors are members of the class B GPCR family. They comprise a heteromer between the GPCR, the calcitonin receptor-like receptor and one of the receptor activity-modifying proteins 1–3. AM plays a significant role in angiogenesis and its antagonist fragment AM22–52 can inhibit blood vessel and tumour growth. The mechanism by which AM interacts with its receptors is unknown. Experimental Approach We determined the AM22–52 binding epitope for the AM1 receptor extracellular domain using biophysical techniques, heteronuclear magnetic resonance spectroscopy and alanine scanning. Key Results Chemical shift perturbation experiments located the main binding epitope for AM22–52 at the AM1 receptor to the C-terminal 8 amino acids. Isothermal titration calorimetry of AM22–52 alanine-substituted peptides indicated that Y52, G51 and I47 are essential for AM1 receptor binding and that K46 and P49 and R44 have a smaller role to play. Characterization of these peptides at the full-length AM receptors was assessed in Cos7 cells by cAMP assay. This confirmed the essential role of Y52, G51 and I47 in binding to the AM1 receptor, with their substitution resulting in ≥100-fold reduction in antagonist potency compared with AM22–52. R44A, K46A, S48A and P49A AM22–52 decreased antagonist potency by approximately 10-fold. Conclusions and Implications This study localizes the main binding epitope of AM22–52 to its C-terminal amino acids and distinguishes essential residues involved in this binding. This will inform the development of improved AM receptor antagonists. PMID:23351143

  2. Atomic spectrometry update - atomic mass spectrometry.

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Bacon, J.; Crain, J. S.; McMahon, A. W.

    The MS and XRF updates have been published together since their introduction in 1988. In the last few years, however, the two sections have been prepared independently of each other and it therefore seemed appropriate to publish the two sections separately. With effect from this issue, the MS Update will appear in the October issue of JAAS and the XRF Update in the November issue. The format used for the MS section is broadly similar to that used last year, with some additional sub-headings. This Update is intended to cover all atomic and stable isotopic MS techniques, but not thosemore » used in studies of fundamental nuclear physics and exotic nuclei far from stability. Also excluded are those reports in which MS is used as a tool in the study of molecular processes and of gaseous components. the review is based on critical selection of developments in instrumentation and methodology, notable for their innovation, originality or achievement of significant advances, and is not intended to be comprehensive in its coverage. Conference papers are only included if they contain enough information to show they meet these criteria, and our policy in general remains one of waiting for a development to appear in a full paper before inclusion in the review. a similar policy applies to foreign language papers unlikely to reach a wide audience. Routine applications of atomic MS are not included in this Update and the reader is referred to the Updates on Industrial Analysis: Metals, Chemicals and Advanced Materials (96/416), Environmental Analysis (96/1444) and Clinical and Biological Materials, Food and Beverages (96/2479). Also excluded are those applications, even if not routine, which use atomic spectroscopy as a tool for the study of a non-atomic property, for example, the use of stable isotope labeling of carbon or nitrogen in biomolecules in metabolic studies. There have been few general reviews on atomic MS of note in the period covered by this update. That of

  3. NASA Update

    NASA Image and Video Library

    2011-02-15

    NASA Administrator Charles F. Bolden Jr., answers questions during a NASA Update on, Tuesday, Feb. 15, 2011, at NASA Headquarters in Washington. Bolden, NASA's 12th Administrator and NASA Deputy Administrator Lori Garver took the time discuss the agency’s fiscal year 2012 budget request and to take questions from employees. Photo Credit: (NASA/Bill Ingalls)

  4. NASA Update

    NASA Image and Video Library

    2011-02-15

    NASA Deputy Associate Administrator for the Office of Communications Bob Jacobs moderates the NASA Update program, Tuesday, Feb. 15, 2011 at NASA Headquarters in Washington. NASA's 12th Administrator Charles Bolden and Deputy Administrator Lori Garver took the time discuss the agency’s fiscal year 2012 budget request and to take questions from employees. Photo Credit: (NASA/Bill Ingalls)

  5. Update to Enhanced Geothermal System Resource Potential Estimate: Preprint

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Augustine, Chad

    2016-10-01

    The deep EGS electricity generation resource potential estimate maintained by the National Renewable Energy Laboratory was updated using the most recent temperature-at-depth maps available from the Southern Methodist University Geothermal Laboratory. The previous study dates back to 2011 and was developed using the original temperature-at-depth maps showcased in the 2006 MIT Future of Geothermal Energy report. The methodology used to update the deep EGS resource potential is the same as in the previous study and is summarized in the paper. The updated deep EGS resource potential estimate was calculated for depths between 3 and 7 km and is binned inmore » 25 degrees C increments. The updated deep EGS electricity generation resource potential estimate is 4,349 GWe. A comparison of the estimates from the previous and updated studies shows a net increase of 117 GWe in the 3-7 km depth range, due mainly to increases in the underlying temperature-at-depth estimates from the updated maps.« less

  6. MutScan: fast detection and visualization of target mutations by scanning FASTQ data.

    PubMed

    Chen, Shifu; Huang, Tanxiao; Wen, Tiexiang; Li, Hong; Xu, Mingyan; Gu, Jia

    2018-01-22

    Some types of clinical genetic tests, such as cancer testing using circulating tumor DNA (ctDNA), require sensitive detection of known target mutations. However, conventional next-generation sequencing (NGS) data analysis pipelines typically involve different steps of filtering, which may cause miss-detection of key mutations with low frequencies. Variant validation is also indicated for key mutations detected by bioinformatics pipelines. Typically, this process can be executed using alignment visualization tools such as IGV or GenomeBrowse. However, these tools are too heavy and therefore unsuitable for validating mutations in ultra-deep sequencing data. We developed MutScan to address problems of sensitive detection and efficient validation for target mutations. MutScan involves highly optimized string-searching algorithms, which can scan input FASTQ files to grab all reads that support target mutations. The collected supporting reads for each target mutation will be piled up and visualized using web technologies such as HTML and JavaScript. Algorithms such as rolling hash and bloom filter are applied to accelerate scanning and make MutScan applicable to detect or visualize target mutations in a very fast way. MutScan is a tool for the detection and visualization of target mutations by only scanning FASTQ raw data directly. Compared to conventional pipelines, this offers a very high performance, executing about 20 times faster, and offering maximal sensitivity since it can grab mutations with even one single supporting read. MutScan visualizes detected mutations by generating interactive pile-ups using web technologies. These can serve to validate target mutations, thus avoiding false positives. Furthermore, MutScan can visualize all mutation records in a VCF file to HTML pages for cloud-friendly VCF validation. MutScan is an open source tool available at GitHub: https://github.com/OpenGene/MutScan.

  7. Lung PET scan

    MedlinePlus

    ... PET - chest; PET - lung; PET - tumor imaging; PET/CT - lung; Solitary pulmonary nodule - PET ... minutes. PET scans are performed along with a CT scan. This is because the combined information from ...

  8. Minnesota's forest statistics, 1987: an inventory update.

    Treesearch

    Jerold T. Hahn; W. Brad Smith

    1987-01-01

    The Minnesota 1987 inventory update, derived by using tree growth models, reports 13.5 million acres of timberland, a decline of less than 1% since 1977. This bulletin presents findings from the inventory update in tables detailing timer land area, volume, and biomass.

  9. Wisconsin's forest statistics, 1987: an inventory update.

    Treesearch

    W. Brad Smith; Jerold T. Hahn

    1989-01-01

    The Wisconsin 1987 inventory update, derived by using tree growth models, reports 14.7 million acres of timberland, a decline of less than 1% since 1983. This bulletin presents findings from the inventory update in tables detailing timberland area, volume, and biomass.

  10. Lidar arc scan uncertainty reduction through scanning geometry optimization

    NASA Astrophysics Data System (ADS)

    Wang, Hui; Barthelmie, Rebecca J.; Pryor, Sara C.; Brown, Gareth.

    2016-04-01

    Doppler lidars are frequently operated in a mode referred to as arc scans, wherein the lidar beam scans across a sector with a fixed elevation angle and the resulting measurements are used to derive an estimate of the n minute horizontal mean wind velocity (speed and direction). Previous studies have shown that the uncertainty in the measured wind speed originates from turbulent wind fluctuations and depends on the scan geometry (the arc span and the arc orientation). This paper is designed to provide guidance on optimal scan geometries for two key applications in the wind energy industry: wind turbine power performance analysis and annual energy production prediction. We present a quantitative analysis of the retrieved wind speed uncertainty derived using a theoretical model with the assumption of isotropic and frozen turbulence, and observations from three sites that are onshore with flat terrain, onshore with complex terrain and offshore, respectively. The results from both the theoretical model and observations show that the uncertainty is scaled with the turbulence intensity such that the relative standard error on the 10 min mean wind speed is about 30 % of the turbulence intensity. The uncertainty in both retrieved wind speeds and derived wind energy production estimates can be reduced by aligning lidar beams with the dominant wind direction, increasing the arc span and lowering the number of beams per arc scan. Large arc spans should be used at sites with high turbulence intensity and/or large wind direction variation.

  11. [A new update of the SIMLII Guidelines on carcinogens].

    PubMed

    Pira, Enrico; Giachino, Gian Mario; Discalzi, Gianluigi

    2011-01-01

    The second update of the Italian Society of Occupational Medicine and Industrial Hygiene (SIMLII) guidelines on Cancerogens and Mutagens, first published in 2003 and reviewed in 2007, is presented. The general setting of the guidelines remaines unmodified. In this new release some important developments on regulatory system, risk assessment, and health surveillance are discussed. The relevant evolution of the regulatory rules is illustrated in detail, with particular reference to the recent implementation in European Union and in Italy of the Regulation (EC) 1272/2008 on Classification, Labelling and Packaging of substances and mixtures. The recent tendencies of the European Scientific Committee on Occupational Exposure Limits in risk assessment, are presented. Some remarks on the use of new biomarkers in health surveillance, with reference to lung and bladder cancer, are discussed. The more recent results on the effectiveness of the use of LDTC scan on screening in asymptomatic persons at high risk for lung cancer, are presented. The use of this imaging technique in health surveillance of special group of workers (i.e., subjects with relevant past asbestos exposure and smokers) could be adopted.

  12. Device localization and dynamic scan plane selection using a wireless MRI detector array

    PubMed Central

    Riffe, Matthew J.; Yutzy, Stephen R.; Jiang, Yun; Twieg, Michael D.; Blumenthal, Colin J.; Hsu, Daniel P.; Pan, Li; Gilson, Wesley D.; Sunshine, Jeffrey L.; Flask, Christopher A.; Duerk, Jeffrey L.; Nakamoto, Dean; Gulani, Vikas; Griswold, Mark A.

    2013-01-01

    Purpose A prototype wireless guidance device using single sideband amplitude modulation (SSB) is presented for a 1.5T MRI system. Methods The device contained three fiducial markers each mounted to an independent receiver coil equipped with wireless SSB technology. Acquiring orthogonal projections of these markers determined the position and orientation of the device, which was used to define the scan plane for a subsequent image acquisition. Device localization and scan plane update required approximately 30 ms, so it could be interleaved with high temporal resolution imaging. Since the wireless device is used for localization and doesn’t require full imaging capability, the design of the SSB wireless system was simplified by allowing an asynchronous clock between the transmitter and receiver. Results When coupled to a high readout bandwidth, the error caused by the lack of a shared frequency reference was quantified to be less than one pixel (0.78 mm) in the projection acquisitions. Image-guidance with the prototype was demonstrated with a phantom where a needle was successfully guided to a target and contrast was delivered. Conclusion The feasibility of active tracking with a wireless detector array is demonstrated. Wireless arrays could be incorporated into devices to assist in image-guided procedures. PMID:23900921

  13. RBC nuclear scan

    MedlinePlus

    ... page: //medlineplus.gov/ency/article/003835.htm RBC nuclear scan To use the sharing features on this page, please enable JavaScript. An RBC nuclear scan uses small amounts of radioactive material to ...

  14. 77 FR 41258 - FOIA Fee Schedule Update

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-13

    ... DEFENSE NUCLEAR FACILITIES SAFETY BOARD 10 CFR Part 1703 FOIA Fee Schedule Update AGENCY: Defense Nuclear Facilities Safety Board. ACTION: Establishment of FOIA Fee Schedule. SUMMARY: The Defense Nuclear Facilities Safety Board is publishing its Freedom of Information Act (FOIA) Fee Schedule Update pursuant to...

  15. 76 FR 43819 - FOIA Fee Schedule Update

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-07-22

    ... DEFENSE NUCLEAR FACILITIES SAFETY BOARD 10 CFR Part 1703 FOIA Fee Schedule Update AGENCY: Defense Nuclear Facilities Safety Board. ACTION: Establishment of FOIA Fee Schedule. SUMMARY: The Defense Nuclear Facilities Safety Board is publishing its Freedom of Information Act (FOIA) Fee Schedule Update pursuant to...

  16. Solar Market Research and Analysis Email Updates | Solar Research | NREL

    Science.gov Websites

    Analysis Email Updates Solar Market Research and Analysis Email Updates NREL's Solar Market email updates, please provide and submit the following information. Email Address

  17. Heart CT scan

    MedlinePlus

    ... Computed tomography scan - heart; Calcium scoring; Multi-detector CT scan - heart; Electron beam computed tomography - heart; Agatston ... table that slides into the center of the CT scanner. You will lie on your back with ...

  18. Human Visuospatial Updating After Passive Translations In Three-Dimensional Space

    PubMed Central

    Klier, Eliana M.; Hess, Bernhard J. M.; Angelaki, Dora E.

    2013-01-01

    To maintain a stable representation of the visual environment as we move, the brain must update the locations of targets in space using extra-retinal signals. Humans can accurately update after intervening active whole-body translations. But can they also update for passive translations (i.e., without efference copy signals of an outgoing motor command)? We asked six head-fixed subjects to remember the location of a briefly flashed target (five possible targets were located at depths of 23, 33, 43, 63 and 150cm in front of the cyclopean eye) as they moved 10cm left, right, up, down, forward or backward, while fixating a head-fixed target at 53cm. After the movement, the subjects made a saccade to the remembered location of the flash with a combination of version and vergence eye movements. We computed an updating ratio where 0 indicates no updating and 1 indicates perfect updating. For lateral and vertical whole-body motion, where updating performance is judged by the size of the version movement, the updating ratios were similar for leftward and rightward translations, averaging 0.84±0.28 (mean±SD), as compared to 0.51±0.33 for downward and 1.05±0.50 for upward translations. For forward/backward movements, where updating performance is judged by the size of the vergence movement, the average updating ratio was 1.12±0.45. Updating ratios tended to be larger for far targets than near targets, although both intra- and inter-subject variabilities were smallest for near targets. Thus, in addition to self-generated movements, extra-retinal signals involving otolith and proprioceptive cues can also be used for spatial constancy. PMID:18256164

  19. Environmental Regulatory Update Table, October 1991

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Houlberg, L.M.; Hawkins, G.T.; Salk, M.S.

    1991-11-01

    The Environmental Regulatory Update Table provides information on regulatory initiatives of interest to DOE operations and contractor staff with environmental management responsibilities. The table is updated each month with information from the Federal Register and other sources, including direct contact with regulatory agencies. Each table entry provides a chronological record of the rulemaking process for that initiative with an abstract and a projection of further action.

  20. Environmental Regulatory Update Table, December 1991

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Houlberg, L.M.; Hawkins, G.T.; Salk, M.S.

    1992-01-01

    The Environmental Regulatory Update Table provides information on regulatory initiatives of interest to DOE operations and contractor staff with environmental management responsibilities. The table is updated each month with information from the Federal Register and other sources, including direct contact with regulatory agencies. Each table entry provides a chronological record of the rulemaking process for that initiative with an abstract and a projection of further action.

  1. Environmental Regulatory Update Table, September 1991

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Houlberg, L.M.; Hawkins, G.T.; Salk, M.S.

    1991-10-01

    The Environmental Regulatory Update Table provides information on regulatory initiatives of interest to DOE operations and contractor staff with environmental management responsibilities. The table is updated each month with information from the Federal Register and other sources, including direct contact with regulatory agencies. Each table entry provides a chronological record of the rulemaking process for that initiative with an abstract and a projection of further action.

  2. Environmental Regulatory Update Table, November 1991

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Houlberg, L.M.; Hawkins, G.T.; Salk, M.S.

    1991-12-01

    The Environmental Regulatory Update Table provides information on regulatory initiatives of interest to DOE operations and contractor staff with environmental management responsibilities. The table is updated each month with information from the Federal Register and other sources, including direct contact with regulatory agencies. Each table entry provides a chronological record of the rulemaking process for that initiative with an abstract and a projection of further action.

  3. DepositScan, a Scanning Program to Measure Spray Deposition Distributions

    USDA-ARS?s Scientific Manuscript database

    DepositScan, a scanning program was developed to quickly measure spray deposit distributions on water sensitive papers or Kromekote cards which are widely used for determinations of pesticide spray deposition quality on target areas. The program is installed in a portable computer and works with a ...

  4. NASA Update

    NASA Image and Video Library

    2009-07-20

    NASA Administrator Charles F. Bolden Jr. left, speaks during his first NASA Update as Deputy Administrator Lori Garver looks on,Tuesday, July 21, 2009, at NASA Headquarters in Washington. Bolden, NASA's 12th Administrator and Garver took the time to introduce themselves and outline their vision for the agency going forward. No questions were taken during the session. Photo Credit: (NASA/Bill Ingalls)

  5. NASA Update

    NASA Image and Video Library

    2009-07-20

    NASA Administrator Charles F. Bolden Jr. left, and Deputy Administrator Lori Garver are seen during their first NASA Update,Tuesday, July 21, 2009, at NASA Headquarters in Washington. Bolden, NASA's 12th Administrator and Garver took the time to introduce themselves and outline their vision for the agency going forward. No questions were taken during the session. Photo Credit: (NASA/Bill Ingalls)

  6. NASA Update

    NASA Image and Video Library

    2009-07-20

    NASA Administrator Charles F. Bolden Jr. speaks during his first NASA Update,Tuesday, July 21, 2009, at NASA Headquarters in Washington. Bolden, NASA's 12th Administrator, was joined by Deputy Administrator Lori Garver where they took the time to introduce themselves and outline their vision for the agency going forward. No questions were taken during the session. Photo Credit: (NASA/Bill Ingalls)

  7. Laser Scanning In Inspection

    NASA Astrophysics Data System (ADS)

    West, Patricia; Baker, Lionel R.

    1989-03-01

    This paper is a review of the applications of laser scanning in inspection. The reasons for the choice of a laser in flying spot scanning and the optical properties of a laser beam which are of value in a scanning instrument will be given. The many methods of scanning laser beams in both one and two dimensions will be described. The use of one dimensional laser scanners for automatic surface inspection for transmitting and reflective products will be covered in detail, with particular emphasis on light collection techniques. On-line inspection applications which will be mentioned include: photographic film web, metal strip products, paper web, glass sheet, car body paint surfaces and internal cylinder bores. Two dimensional laser scanning is employed in applications where increased resolution, increased depth of focus, and better contrast are required compared with conventional vidicon TV or solid state array cameras. Such examples as special microscope laser scanning systems and a TV compatible system for use in restricted areas of a nuclear reactor will be described. The technical and economic benefits and limitations of laser scanning video systems will be compared with conventional TV and CCD array devices.

  8. NXE pellicle: development update

    NASA Astrophysics Data System (ADS)

    Brouns, Derk; Bendiksen, Aage; Broman, Par; Casimiri, Eric; Colsters, Paul; de Graaf, Dennis; Harrold, Hilary; Hennus, Piet; Janssen, Paul; Kramer, Ronald; Kruizinga, Matthias; Kuntzel, Henk; Lafarre, Raymond; Mancuso, Andrea; Ockwell, David; Smith, Daniel; van de Weg, David; Wiley, Jim

    2016-09-01

    ASML introduced the NXE pellicle concept, a removable pellicle solution that is compatible with current and future patterned mask inspection methods. We will present results of how we have taken the idea from concept to a demonstrated solution enabling the use of EUV pellicle by the industry for high volume manufacturing. We will update on the development of the next generation of pellicle films with higher power capability. Further, we will provide an update on top level requirements for pellicles and external interface requirements needed to support NXE pellicle adoption at a mask shop. Finally, we will present ASML's pellicle handling equipment to enable pellicle use at mask shops and our NXE pellicle roadmap outlining future improvements.

  9. Wide scanning spherical antenna

    NASA Technical Reports Server (NTRS)

    Shen, Bing (Inventor); Stutzman, Warren L. (Inventor)

    1995-01-01

    A novel method for calculating the surface shapes for subreflectors in a suboptic assembly of a tri-reflector spherical antenna system is introduced, modeled from a generalization of Galindo-Israel's method of solving partial differential equations to correct for spherical aberration and provide uniform feed to aperture mapping. In a first embodiment, the suboptic assembly moves as a single unit to achieve scan while the main reflector remains stationary. A feed horn is tilted during scan to maintain the illuminated area on the main spherical reflector fixed throughout the scan thereby eliminating the need to oversize the main spherical reflector. In an alternate embodiment, both the main spherical reflector and the suboptic assembly are fixed. A flat mirror is used to create a virtual image of the suboptic assembly. Scan is achieved by rotating the mirror about the spherical center of the main reflector. The feed horn is tilted during scan to maintain the illuminated area on the main spherical reflector fixed throughout the scan.

  10. Stereo Science Update

    NASA Image and Video Library

    2009-04-13

    Angelo Vourlidas, project scientist, Sun Earth Connection Coronal and Heliospheric Investigation, at the Naval Research Laboratory makes a comment during a Science Update on the STEREO mission at NASA Headquarters in Washington, Tuesday, April 14, 2009. Photo Credit: (NASA/Paul E. Alers)

  11. Cultural practices updates

    USDA-ARS?s Scientific Manuscript database

    Cultural practice updates from 2013 included the effects of shredding in spring, residue management, periodic flooding, no-till fertilizer applications, and billet planting on cane tonnage and sugar yield. Shredding, whether high or low, had little impacts in 2013. However, burning following shreddi...

  12. Stereo Science Update

    NASA Image and Video Library

    2009-04-13

    Toni Galvin, principal investigator, Plasma and Superthermal Ion Composition instrument at the University of New Hampshire makes a comment during a Science Update on the STEREO mission at NASA Headquarters in Washington, Tuesday, April 14, 2009. Photo Credit: (NASA/Paul E. Alers)

  13. Consensus and update on the definition of on-treatment platelet reactivity to adenosine diphosphate associated with ischemia and bleeding.

    PubMed

    Tantry, Udaya S; Bonello, Laurent; Aradi, Daniel; Price, Matthew J; Jeong, Young-Hoon; Angiolillo, Dominick J; Stone, Gregg W; Curzen, Nick; Geisler, Tobias; Ten Berg, Jurrien; Kirtane, Ajay; Siller-Matula, Jolanta; Mahla, Elisabeth; Becker, Richard C; Bhatt, Deepak L; Waksman, Ron; Rao, Sunil V; Alexopoulos, Dimitrios; Marcucci, Rossella; Reny, Jean-Luc; Trenk, Dietmar; Sibbing, Dirk; Gurbel, Paul A

    2013-12-17

    Dual antiplatelet therapy with aspirin and a P2Y12 receptor blocker is a key strategy to reduce platelet reactivity and to prevent thrombotic events in patients treated with percutaneous coronary intervention. In an earlier consensus document, we proposed cutoff values for high on-treatment platelet reactivity to adenosine diphosphate (ADP) associated with post-percutaneous coronary intervention ischemic events for various platelet function tests (PFTs). Updated American and European practice guidelines have issued a Class IIb recommendation for PFT to facilitate the choice of P2Y12 receptor inhibitor in selected high-risk patients treated with percutaneous coronary intervention, although routine testing is not recommended (Class III). Accumulated data from large studies underscore the importance of high on-treatment platelet reactivity to ADP as a prognostic risk factor. Recent prospective randomized trials of PFT did not demonstrate clinical benefit, thus questioning whether treatment modification based on the results of current PFT platforms can actually influence outcomes. However, there are major limitations associated with these randomized trials. In addition, recent data suggest that low on-treatment platelet reactivity to ADP is associated with a higher risk of bleeding. Therefore, a therapeutic window concept has been proposed for P2Y12 inhibitor therapy. In this updated consensus document, we review the available evidence addressing the relation of platelet reactivity to thrombotic and bleeding events. In addition, we propose cutoff values for high and low on-treatment platelet reactivity to ADP that might be used in future investigations of personalized antiplatelet therapy. Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  14. Lidar arc scan uncertainty reduction through scanning geometry optimization

    DOE PAGES

    Wang, Hui; Barthelmie, Rebecca J.; Pryor, Sara C.; ...

    2016-04-13

    Doppler lidars are frequently operated in a mode referred to as arc scans, wherein the lidar beam scans across a sector with a fixed elevation angle and the resulting measurements are used to derive an estimate of the n minute horizontal mean wind velocity (speed and direction). Previous studies have shown that the uncertainty in the measured wind speed originates from turbulent wind fluctuations and depends on the scan geometry (the arc span and the arc orientation). This paper is designed to provide guidance on optimal scan geometries for two key applications in the wind energy industry: wind turbine power performance analysis and annualmore » energy production prediction. We present a quantitative analysis of the retrieved wind speed uncertainty derived using a theoretical model with the assumption of isotropic and frozen turbulence, and observations from three sites that are onshore with flat terrain, onshore with complex terrain and offshore, respectively. The results from both the theoretical model and observations show that the uncertainty is scaled with the turbulence intensity such that the relative standard error on the 10 min mean wind speed is about 30% of the turbulence intensity. The uncertainty in both retrieved wind speeds and derived wind energy production estimates can be reduced by aligning lidar beams with the dominant wind direction, increasing the arc span and lowering the number of beams per arc scan. As a result, large arc spans should be used at sites with high turbulence intensity and/or large wind direction variation.« less

  15. Lidar arc scan uncertainty reduction through scanning geometry optimization

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Wang, Hui; Barthelmie, Rebecca J.; Pryor, Sara C.

    Doppler lidars are frequently operated in a mode referred to as arc scans, wherein the lidar beam scans across a sector with a fixed elevation angle and the resulting measurements are used to derive an estimate of the n minute horizontal mean wind velocity (speed and direction). Previous studies have shown that the uncertainty in the measured wind speed originates from turbulent wind fluctuations and depends on the scan geometry (the arc span and the arc orientation). This paper is designed to provide guidance on optimal scan geometries for two key applications in the wind energy industry: wind turbine power performance analysis and annualmore » energy production prediction. We present a quantitative analysis of the retrieved wind speed uncertainty derived using a theoretical model with the assumption of isotropic and frozen turbulence, and observations from three sites that are onshore with flat terrain, onshore with complex terrain and offshore, respectively. The results from both the theoretical model and observations show that the uncertainty is scaled with the turbulence intensity such that the relative standard error on the 10 min mean wind speed is about 30% of the turbulence intensity. The uncertainty in both retrieved wind speeds and derived wind energy production estimates can be reduced by aligning lidar beams with the dominant wind direction, increasing the arc span and lowering the number of beams per arc scan. As a result, large arc spans should be used at sites with high turbulence intensity and/or large wind direction variation.« less

  16. Scanning Seismic Intrusion Detector

    NASA Technical Reports Server (NTRS)

    Lee, R. D.

    1982-01-01

    Scanning seismic intrusion detector employs array of automatically or manually scanned sensors to determine approximate location of intruder. Automatic-scanning feature enables one operator to tend system of many sensors. Typical sensors used with new system are moving-coil seismic pickups. Detector finds uses in industrial security systems.

  17. Neural mechanisms of reactivation-induced updating that enhance and distort memory

    PubMed Central

    St. Jacques, Peggy L.; Olm, Christopher; Schacter, Daniel L.

    2013-01-01

    We remember a considerable number of personal experiences because we are frequently reminded of them, a process known as memory reactivation. Although memory reactivation helps to stabilize and update memories, reactivation may also introduce distortions if novel information becomes incorporated with memory. Here we used functional magnetic resonance imaging (fMRI) to investigate the neural mechanisms mediating reactivation-induced updating in memory for events experienced during a museum tour. During scanning, participants were shown target photographs to reactivate memories from the museum tour followed by a novel lure photograph from an alternate tour. Later, participants were presented with target and lure photographs and asked to determine whether the photographs showed a stop they visited during the tour. We used a subsequent memory analysis to examine neural recruitment during reactivation that was associated with later true and false memories. We predicted that the quality of reactivation, as determined by online ratings of subjective recollection, would increase subsequent true memories but also facilitate incorporation of the lure photograph, thereby increasing subsequent false memories. The fMRI results revealed that the quality of reactivation modulated subsequent true and false memories via recruitment of left posterior parahippocampal, bilateral retrosplenial, and bilateral posterior inferior parietal cortices. However, the timing of neural recruitment and the way in which memories were reactivated contributed to differences in whether memory reactivation led to distortions or not. These data reveal the neural mechanisms recruited during memory reactivation that modify how memories will be subsequently retrieved, supporting the flexible and dynamic aspects of memory. PMID:24191059

  18. Neural mechanisms of reactivation-induced updating that enhance and distort memory.

    PubMed

    St Jacques, Peggy L; Olm, Christopher; Schacter, Daniel L

    2013-12-03

    We remember a considerable number of personal experiences because we are frequently reminded of them, a process known as memory reactivation. Although memory reactivation helps to stabilize and update memories, reactivation may also introduce distortions if novel information becomes incorporated with memory. Here we used functional magnetic resonance imaging (fMRI) to investigate the neural mechanisms mediating reactivation-induced updating in memory for events experienced during a museum tour. During scanning, participants were shown target photographs to reactivate memories from the museum tour followed by a novel lure photograph from an alternate tour. Later, participants were presented with target and lure photographs and asked to determine whether the photographs showed a stop they visited during the tour. We used a subsequent memory analysis to examine neural recruitment during reactivation that was associated with later true and false memories. We predicted that the quality of reactivation, as determined by online ratings of subjective recollection, would increase subsequent true memories but also facilitate incorporation of the lure photograph, thereby increasing subsequent false memories. The fMRI results revealed that the quality of reactivation modulated subsequent true and false memories via recruitment of left posterior parahippocampal, bilateral retrosplenial, and bilateral posterior inferior parietal cortices. However, the timing of neural recruitment and the way in which memories were reactivated contributed to differences in whether memory reactivation led to distortions or not. These data reveal the neural mechanisms recruited during memory reactivation that modify how memories will be subsequently retrieved, supporting the flexible and dynamic aspects of memory.

  19. Legislative Update, December 2009. Report 09-26

    ERIC Educational Resources Information Center

    Blair, Julia

    2009-01-01

    This update contains analyses of legislative initiatives being tracked by the staff of the California Postsecondary Education Commission (CPEC). At its December 15 meeting, CPEC staff provided an update on the priority higher education legislation, including recent amendments. A matrix of bills monitored by CPEC staff is included. Contents…

  20. 40 CFR 68.36 - Review and update.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 15 2011-07-01 2011-07-01 false Review and update. 68.36 Section 68.36 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) CHEMICAL ACCIDENT PREVENTION PROVISIONS Hazard Assessment § 68.36 Review and update. (a) The owner or operator shall...

  1. 40 CFR 68.36 - Review and update.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 16 2012-07-01 2012-07-01 false Review and update. 68.36 Section 68.36 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) CHEMICAL ACCIDENT PREVENTION PROVISIONS Hazard Assessment § 68.36 Review and update. (a) The owner or operator shall...

  2. 40 CFR 68.36 - Review and update.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 16 2013-07-01 2013-07-01 false Review and update. 68.36 Section 68.36 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) CHEMICAL ACCIDENT PREVENTION PROVISIONS Hazard Assessment § 68.36 Review and update. (a) The owner or operator shall...

  3. 40 CFR 68.36 - Review and update.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 16 2014-07-01 2014-07-01 false Review and update. 68.36 Section 68.36 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) CHEMICAL ACCIDENT PREVENTION PROVISIONS Hazard Assessment § 68.36 Review and update. (a) The owner or operator shall...

  4. Proteinase-activated receptors (PARs) – focus on receptor-receptor-interactions and their physiological and pathophysiological impact

    PubMed Central

    2013-01-01

    Proteinase-activated receptors (PARs) are a subfamily of G protein-coupled receptors (GPCRs) with four members, PAR1, PAR2, PAR3 and PAR4, playing critical functions in hemostasis, thrombosis, embryonic development, wound healing, inflammation and cancer progression. PARs are characterized by a unique activation mechanism involving receptor cleavage by different proteinases at specific sites within the extracellular amino-terminus and the exposure of amino-terminal “tethered ligand“ domains that bind to and activate the cleaved receptors. After activation, the PAR family members are able to stimulate complex intracellular signalling networks via classical G protein-mediated pathways and beta-arrestin signalling. In addition, different receptor crosstalk mechanisms critically contribute to a high diversity of PAR signal transduction and receptor-trafficking processes that result in multiple physiological effects. In this review, we summarize current information about PAR-initiated physical and functional receptor interactions and their physiological and pathological roles. We focus especially on PAR homo- and heterodimerization, transactivation of receptor tyrosine kinases (RTKs) and receptor serine/threonine kinases (RSTKs), communication with other GPCRs, toll-like receptors and NOD-like receptors, ion channel receptors, and on PAR association with cargo receptors. In addition, we discuss the suitability of these receptor interaction mechanisms as targets for modulating PAR signalling in disease. PMID:24215724

  5. The New Weather Radar for America's Space Program in Florida: A Temperature Profile Adaptive Scan Strategy

    NASA Technical Reports Server (NTRS)

    Carey, L. D.; Petersen, W. A.; Deierling, W.; Roeder, W. P.

    2009-01-01

    A new weather radar is being acquired for use in support of America s space program at Cape Canaveral Air Force Station, NASA Kennedy Space Center, and Patrick AFB on the east coast of central Florida. This new radar replaces the modified WSR-74C at Patrick AFB that has been in use since 1984. The new radar is a Radtec TDR 43-250, which has Doppler and dual polarization capability. A new fixed scan strategy was designed to best support the space program. The fixed scan strategy represents a complex compromise between many competing factors and relies on climatological heights of various temperatures that are important for improved lightning forecasting and evaluation of Lightning Launch Commit Criteria (LCC), which are the weather rules to avoid lightning strikes to in-flight rockets. The 0 C to -20 C layer is vital since most generation of electric charge occurs within it and so it is critical in evaluating Lightning LCC and in forecasting lightning. These are two of the most important duties of 45 WS. While the fixed scan strategy that covers most of the climatological variation of the 0 C to -20 C levels with high resolution ensures that these critical temperatures are well covered most of the time, it also means that on any particular day the radar is spending precious time scanning at angles covering less important heights. The goal of this project is to develop a user-friendly, Interactive Data Language (IDL) computer program that will automatically generate optimized radar scan strategies that adapt to user input of the temperature profile and other important parameters. By using only the required scan angles output by the temperature profile adaptive scan strategy program, faster update times for volume scans and/or collection of more samples per gate for better data quality is possible, while maintaining high resolution at the critical temperature levels. The temperature profile adaptive technique will also take into account earth curvature and refraction

  6. Environmental Regulatory Update Table, August 1991

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Houlberg, L.M., Hawkins, G.T.; Salk, M.S.

    1991-09-01

    This Environmental Regulatory Update Table (August 1991) provides information on regulatory initiatives of interest to DOE operations and contractor staff with environmental management responsibilities. The table is updated each month with information from the Federal Register and other sources, including direct contact with regulatory agencies. Each table entry provides a chronological record of the rulemaking process for that initiative with an abstract and a projection of further action.

  7. Excitation-scanning hyperspectral imaging microscope

    PubMed Central

    Favreau, Peter F.; Hernandez, Clarissa; Heaster, Tiffany; Alvarez, Diego F.; Rich, Thomas C.; Prabhat, Prashant; Leavesley, Silas J.

    2014-01-01

    Abstract. Hyperspectral imaging is a versatile tool that has recently been applied to a variety of biomedical applications, notably live-cell and whole-tissue signaling. Traditional hyperspectral imaging approaches filter the fluorescence emission over a broad wavelength range while exciting at a single band. However, these emission-scanning approaches have shown reduced sensitivity due to light attenuation from spectral filtering. Consequently, emission scanning has limited applicability for time-sensitive studies and photosensitive applications. In this work, we have developed an excitation-scanning hyperspectral imaging microscope that overcomes these limitations by providing high transmission with short acquisition times. This is achieved by filtering the fluorescence excitation rather than the emission. We tested the efficacy of the excitation-scanning microscope in a side-by-side comparison with emission scanning for detection of green fluorescent protein (GFP)-expressing endothelial cells in highly autofluorescent lung tissue. Excitation scanning provided higher signal-to-noise characteristics, as well as shorter acquisition times (300  ms/wavelength band with excitation scanning versus 3  s/wavelength band with emission scanning). Excitation scanning also provided higher delineation of nuclear and cell borders, and increased identification of GFP regions in highly autofluorescent tissue. These results demonstrate excitation scanning has utility in a wide range of time-dependent and photosensitive applications. PMID:24727909

  8. Excitation-scanning hyperspectral imaging microscope.

    PubMed

    Favreau, Peter F; Hernandez, Clarissa; Heaster, Tiffany; Alvarez, Diego F; Rich, Thomas C; Prabhat, Prashant; Leavesley, Silas J

    2014-04-01

    Hyperspectral imaging is a versatile tool that has recently been applied to a variety of biomedical applications, notably live-cell and whole-tissue signaling. Traditional hyperspectral imaging approaches filter the fluorescence emission over a broad wavelength range while exciting at a single band. However, these emission-scanning approaches have shown reduced sensitivity due to light attenuation from spectral filtering. Consequently, emission scanning has limited applicability for time-sensitive studies and photosensitive applications. In this work, we have developed an excitation-scanning hyperspectral imaging microscope that overcomes these limitations by providing high transmission with short acquisition times. This is achieved by filtering the fluorescence excitation rather than the emission. We tested the efficacy of the excitation-scanning microscope in a side-by-side comparison with emission scanning for detection of green fluorescent protein (GFP)-expressing endothelial cells in highly autofluorescent lung tissue. Excitation scanning provided higher signal-to-noise characteristics, as well as shorter acquisition times (300  ms/wavelength band with excitation scanning versus 3  s/wavelength band with emission scanning). Excitation scanning also provided higher delineation of nuclear and cell borders, and increased identification of GFP regions in highly autofluorescent tissue. These results demonstrate excitation scanning has utility in a wide range of time-dependent and photosensitive applications.

  9. COPPER RESEARCH UPDATE

    EPA Science Inventory

    This presentation provides an update and overview of new research results and remaining research needs with respect to copper corrosion control issues. The topics to be covered include: occurrence of elevated copper release in systems that meet the Action Level; impact of water c...

  10. Imaging dopamine D3 receptors in the human brain with positron emission tomography, [11C]PHNO, and a selective D3 receptor antagonist.

    PubMed

    Searle, Graham; Beaver, John D; Comley, Robert A; Bani, Massimo; Tziortzi, Andri; Slifstein, Mark; Mugnaini, Manolo; Griffante, Cristiana; Wilson, Alan A; Merlo-Pich, Emilio; Houle, Sylvain; Gunn, Roger; Rabiner, Eugenii A; Laruelle, Marc

    2010-08-15

    Dopamine D(3) receptors are involved in the pathophysiology of several neuropsychiatric conditions. [(11)C]-(+)-PHNO is a radiolabeled D(2) and D(3) agonist, suitable for imaging the agonist binding sites (denoted D(2HIGH) and D(3)) of these receptors with positron emission tomography (PET). PET studies in nonhuman primates documented that, in vivo, [(11)C]-(+)-PHNO displays a relative selectivity for D(3) compared with D(2HIGH) receptor sites and that the [(11)C]-(+)-PHNO signal is enriched in D(3) contribution compared with conventional ligands such as [(11)C] raclopride. To define the D(3) contribution (f(PHNO)(D3)) to [(11)C]-(+)-PHNO binding potential (BP(ND)) in healthy humans, 52 PET scans were obtained in 19 healthy volunteers at baseline and following oral administration of various doses of the selective D(3) receptor antagonist, GSK598809. The impact of GSK598809 on [(11)C]-(+)-PHNO was regionally selective. In dorsal regions of the striatum, GSK598809 did not significantly affect [(11)C]-(+)-PHNO BP(ND) (f(PHNO)(D3) approximately 0%). Conversely, in the substantia nigra, GSK598809 dose-dependently reduced [(11)C]-(+)-PHNO binding to nonspecific level (f(PHNO)(D3) approximately 100%). In ventral striatum (VST), globus pallidus and thalamus (THA), [(11)C]-(+)-PHNO BP(ND) was attributable to a combination of D(2HIGH) and D(3) receptor sites, with f(PHNO)(D3) of 26%, 67% and 46%, respectively. D(3) receptor binding potential (BP(ND)(D3)) was highest in globus pallidus (1.90) and substantial nigra (1.39), with lower levels in VST (.77) and THA (.18) and negligible levels in dorsal striatum. This study elucidated the pharmacologic nature of the [(11)C]-(+)-PHNO signal in healthy subjects and provided the first quantification of D(3) receptor availability with PET in the living human brain. Copyright 2010 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  11. 18 CFR 154.311 - Updating of statements.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 18 Conservation of Power and Water Resources 1 2014-04-01 2014-04-01 false Updating of statements. 154.311 Section 154.311 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION... Changes § 154.311 Updating of statements. (a) Certain statements and schedules in § 154.312, that include...

  12. 18 CFR 154.311 - Updating of statements.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 18 Conservation of Power and Water Resources 1 2012-04-01 2012-04-01 false Updating of statements. 154.311 Section 154.311 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION... Changes § 154.311 Updating of statements. (a) Certain statements and schedules in § 154.312, that include...

  13. 18 CFR 154.311 - Updating of statements.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 18 Conservation of Power and Water Resources 1 2013-04-01 2013-04-01 false Updating of statements. 154.311 Section 154.311 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION... Changes § 154.311 Updating of statements. (a) Certain statements and schedules in § 154.312, that include...

  14. 18 CFR 154.311 - Updating of statements.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 18 Conservation of Power and Water Resources 1 2011-04-01 2011-04-01 false Updating of statements. 154.311 Section 154.311 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION... Changes § 154.311 Updating of statements. (a) Certain statements and schedules in § 154.312, that include...

  15. 18 CFR 154.311 - Updating of statements.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 18 Conservation of Power and Water Resources 1 2010-04-01 2010-04-01 false Updating of statements. 154.311 Section 154.311 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION... Changes § 154.311 Updating of statements. (a) Certain statements and schedules in § 154.312, that include...

  16. Spatial Updating of Environments Described in Texts

    ERIC Educational Resources Information Center

    Avraamides, Marios N.

    2003-01-01

    People update egocentric spatial relations in an effortless and on-line manner when they move in the environment, but not when they only imagine themselves moving. In contrast to previous studies, the present experiments examined egocentric updating with spatial scenes that were encoded linguistically instead of perceived directly. Experiment 1…

  17. 10 CFR 474.5 - Review and Update

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 10 Energy 3 2010-01-01 2010-01-01 false Review and Update 474.5 Section 474.5 Energy DEPARTMENT OF ENERGY ENERGY CONSERVATION ELECTRIC AND HYBRID VEHICLE RESEARCH, DEVELOPMENT, AND DEMONSTRATION PROGRAM; PETROLEUM-EQUIVALENT FUEL ECONOMY CALCULATION § 474.5 Review and Update The Department will review Part 474...

  18. 10 CFR 474.5 - Review and Update

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 10 Energy 3 2014-01-01 2014-01-01 false Review and Update 474.5 Section 474.5 Energy DEPARTMENT OF ENERGY ENERGY CONSERVATION ELECTRIC AND HYBRID VEHICLE RESEARCH, DEVELOPMENT, AND DEMONSTRATION PROGRAM; PETROLEUM-EQUIVALENT FUEL ECONOMY CALCULATION § 474.5 Review and Update The Department will review part 474...

  19. 10 CFR 474.5 - Review and Update

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 10 Energy 3 2012-01-01 2012-01-01 false Review and Update 474.5 Section 474.5 Energy DEPARTMENT OF ENERGY ENERGY CONSERVATION ELECTRIC AND HYBRID VEHICLE RESEARCH, DEVELOPMENT, AND DEMONSTRATION PROGRAM; PETROLEUM-EQUIVALENT FUEL ECONOMY CALCULATION § 474.5 Review and Update The Department will review part 474...

  20. 10 CFR 474.5 - Review and Update

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 10 Energy 3 2013-01-01 2013-01-01 false Review and Update 474.5 Section 474.5 Energy DEPARTMENT OF ENERGY ENERGY CONSERVATION ELECTRIC AND HYBRID VEHICLE RESEARCH, DEVELOPMENT, AND DEMONSTRATION PROGRAM; PETROLEUM-EQUIVALENT FUEL ECONOMY CALCULATION § 474.5 Review and Update The Department will review part 474...

  1. 10 CFR 474.5 - Review and Update

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 10 Energy 3 2011-01-01 2011-01-01 false Review and Update 474.5 Section 474.5 Energy DEPARTMENT OF ENERGY ENERGY CONSERVATION ELECTRIC AND HYBRID VEHICLE RESEARCH, DEVELOPMENT, AND DEMONSTRATION PROGRAM; PETROLEUM-EQUIVALENT FUEL ECONOMY CALCULATION § 474.5 Review and Update The Department will review Part 474...

  2. 42 CFR 414.30 - Conversion factor update.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 3 2010-10-01 2010-10-01 false Conversion factor update. 414.30 Section 414.30 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Practitioners § 414.30 Conversion factor update. Unless Congress acts in accordance with section 1848(d)(3) of...

  3. 42 CFR 414.30 - Conversion factor update.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 3 2011-10-01 2011-10-01 false Conversion factor update. 414.30 Section 414.30 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Practitioners § 414.30 Conversion factor update. Unless Congress acts in accordance with section 1848(d)(3) of...

  4. 75 FR 17641 - Updating Fire Safety Standards

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-07

    ... DEPARTMENT OF VETERANS AFFAIRS 38 CFR Parts 17 and 59 RIN 2900-AN57 Updating Fire Safety Standards... for VA approval of such facilities, including standards for fire safety and heating and cooling... submitted in response to ``RIN 2900-AN57--Updating Fire Safety Standards.'' Copies of comments received will...

  5. 10 CFR 61.22 - Updating of application.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 10 Energy 2 2010-01-01 2010-01-01 false Updating of application. 61.22 Section 61.22 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) LICENSING REQUIREMENTS FOR LAND DISPOSAL OF RADIOACTIVE WASTE Licenses § 61.22 Updating of application. (a) The application must be as complete as possible in the light...

  6. 10 CFR 61.22 - Updating of application.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 10 Energy 2 2014-01-01 2014-01-01 false Updating of application. 61.22 Section 61.22 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) LICENSING REQUIREMENTS FOR LAND DISPOSAL OF RADIOACTIVE WASTE Licenses § 61.22 Updating of application. (a) The application must be as complete as possible in the light...

  7. 10 CFR 61.22 - Updating of application.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 10 Energy 2 2013-01-01 2013-01-01 false Updating of application. 61.22 Section 61.22 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) LICENSING REQUIREMENTS FOR LAND DISPOSAL OF RADIOACTIVE WASTE Licenses § 61.22 Updating of application. (a) The application must be as complete as possible in the light...

  8. 10 CFR 61.22 - Updating of application.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 10 Energy 2 2011-01-01 2011-01-01 false Updating of application. 61.22 Section 61.22 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) LICENSING REQUIREMENTS FOR LAND DISPOSAL OF RADIOACTIVE WASTE Licenses § 61.22 Updating of application. (a) The application must be as complete as possible in the light...

  9. 10 CFR 61.22 - Updating of application.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 10 Energy 2 2012-01-01 2012-01-01 false Updating of application. 61.22 Section 61.22 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) LICENSING REQUIREMENTS FOR LAND DISPOSAL OF RADIOACTIVE WASTE Licenses § 61.22 Updating of application. (a) The application must be as complete as possible in the light...

  10. Update on the pathophysiological activities of the cardiac molecule cardiotrophin-1 in obesity.

    PubMed

    Asrih, Mohamed; Mach, François; Quercioli, Alessandra; Dallegri, Franco; Montecucco, Fabrizio

    2013-01-01

    Cardiotrophin-1 (CT-1) is a heart-targeting cytokine that has been reported to exert a variety of activities also in other organs such as the liver, adipose tissue, and atherosclerotic arteries. CT-1 has been shown to induce these effects via binding to a transmembrane receptor, comprising the leukaemia inhibitory factor receptor (LIFR β ) subunit and the glycoprotein 130 (gp130, a common signal transducer). Both local and systemic concentrations of CT-1 have been shown to potentially play a critical role in obesity. For instance, CT-1 plasma concentrations have been shown to be increased in metabolic syndrome (a cluster disease including obesity) probably due to adipose tissue overexpression. Interestingly, treatment with exogenous CT-1 has been shown to improve lipid and glucose metabolism in animal models of obesity. These benefits might suggest a potential therapeutic role for CT-1. However, beyond its beneficial properties, CT-1 has been also shown to induce some adverse effects, such as cardiac hypertrophy and adipose tissue inflammation. Although scientific evidence is still needed, CT-1 might be considered as a potential example of damage/danger-associated molecular pattern (DAMP) in obesity-related cardiovascular diseases. In this narrative review, we aimed at discussing and updating evidence from basic research on the pathophysiological and potential therapeutic roles of CT-1 in obesity.

  11. Pyrimidinergic Receptor Activation Controls Toxoplasma gondii Infection in Macrophages

    PubMed Central

    Moreira-Souza, Aline Cristina Abreu; Marinho, Ygor; Correa, Gladys; Santoro, Giani França; Coutinho, Claudia Mara Lara Melo; Vommaro, Rossiane Claudia; Coutinho-Silva, Robson

    2015-01-01

    Infection by the protozoan parasite Toxoplasma gondii is highly prevalent worldwide and may have serious clinical manifestations in immunocompromised patients. T. gondii is an obligate intracellular parasite that infects almost any cell type in mammalian hosts, including immune cells. The immune cells express purinergic P2 receptors in their membrane – subdivided into P2Y and P2X subfamilies - whose activation is important for infection control. Here, we examined the effect of treatment with UTP and UDP in mouse peritoneal macrophages infected with T. gondii tachyzoites. Treatment with these nucleotides reduced parasitic load by 90%, but did not increase the levels of the inflammatory mediators NO and ROS, nor did it modulate host cell death by apoptosis or necrosis. On the other hand, UTP and UDP treatments induced early egress of tachyzoites from infected macrophages, in a Ca2+-dependent manner, as shown by scanning electron microscopy analysis, and videomicroscopy. In subsequent infections, prematurely egressed parasites had reduced infectivity, and could neither replicate nor inhibit the fusion of lysosomes to the parasitophorous vacuole. The use of selective agonists and antagonists of the receptor subtypes P2Y2 and P2Y4 and P2Y6 showed that premature parasite egress may be mediated by the activation of these receptor subtypes. Our results suggest that the activity of P2Y host cell receptors controls T. gondii infection in macrophages, highlighting the importance of pyrimidinergic signaling for innate immune system response against infection. Finally the P2Y receptors should be considered as new target for the development of drugs against T. gondii infection. PMID:26192447

  12. NASA Update

    NASA Image and Video Library

    2009-07-20

    NASA Deputy Administrator Lori Garver, right, looks on as NASA Administrator Charles F. Bolden Jr. speaks during his first NASA Update,Tuesday, July 21, 2009, at NASA Headquarters in Washington. Bolden, NASA's 12th Administrator and Garver took the time to introduce themselves and outline their vision for the agency going forward. No questions were taken during the session. Photo Credit: (NASA/Bill Ingalls)

  13. NASA Update

    NASA Image and Video Library

    2009-07-20

    NASA Deputy Administrator Lori Garver, second right on stage, speaks as NASA Administrator Charles F. Bolden Jr. looks on during a NASA Update,Tuesday, July 21, 2009, at NASA Headquarters in Washington. Bolden, NASA's 12th Administrator and Garver took the time to introduce themselves and outline their vision for the agency going forward. No questions were taken during the session. Photo Credit: (NASA/Bill Ingalls)

  14. NASA Update

    NASA Image and Video Library

    2009-07-20

    NASA Administrator Charles F. Bolden Jr. left on stage, speaks during his first NASA Update as Deputy Administrator Lori Garver looks on at right,Tuesday, July 21, 2009, at NASA Headquarters in Washington. Bolden, NASA's 12th Administrator and Garver took the time to introduce themselves and outline their vision for the agency going forward. No questions were taken during the session. Photo Credit: (NASA/Bill Ingalls)

  15. NASA Update

    NASA Image and Video Library

    2009-07-20

    NASA Administrator Charles F. Bolden Jr., left on stage, speaks during his first NASA Update as Deputy Administrator Lori Garver looks on at right,Tuesday, July 21, 2009, at NASA Headquarters in Washington. Bolden, NASA's 12th Administrator and Garver took the time to introduce themselves and outline their vision for the agency going forward. No questions were taken during the session. Photo Credit: (NASA/Bill Ingalls)

  16. NASA Update

    NASA Image and Video Library

    2009-07-20

    NASA Deputy Administrator Lori Garver makes a point as she speaks during a NASA Update with Administrator Charles F. Bolden Jr.,Tuesday, July 21, 2009, at NASA Headquarters in Washington. Bolden, NASA's 12th Administrator and Garver took the time to introduce themselves and outline their vision for the agency going forward. No questions were taken during the session. Photo Credit: (NASA/Bill Ingalls)

  17. NASA Update

    NASA Image and Video Library

    2009-07-20

    Alan Ladwig, Senior Advisor to the NASA Administrator, introduces Administrator Charles F. Bolden Jr. and Deputy Administrator Lori Garver at a NASA Update,Tuesday, July 21, 2009, at NASA Headquarters in Washington. Bolden, the agency's 12th Administrator and Garver took the time to introduce themselves and outline their vision for the agency going forward. No questions were taken during the session. Photo Credit: (NASA/Bill Ingalls)

  18. Diverse roles of integrin receptors in articular cartilage.

    PubMed

    Shakibaei, M; Csaki, C; Mobasheri, A

    2008-01-01

    Integrins are heterodimeric integral membrane proteins made up of alpha and beta subunits. At least eighteen alpha and eight beta subunit genes have been described in mammals. Integrin family members are plasma membrane receptors involved in cell adhesion and active as intra- and extracellular signalling molecules in a variety of processes including embryogenesis, hemostasis, tissue repair, immune response and metastatic spread of tumour cells. Integrin beta 1 (beta1-integrin), the protein encoded by the ITGB1 gene (also known as CD29 and VLAB), is a multi-functional protein involved in cell-matrix adhesion, cell signalling, cellular defense, cell adhesion, protein binding, protein heterodimerisation and receptor-mediated activity. It is highly expressed in the human body (17.4 times higher than the average gene in the last updated revision of the human genome). The extracellular matrix (ECM) of articular cartilage is a unique environment. Interactions between chondrocytes and the ECM regulate many biological processes important to homeostasis and repair of articular cartilage, including cell attachment, growth, differentiation and survival. The beta1-integrin family of cell surface receptors appears to play a major role in mediating cell-matrix interactions that are important in regulating these fundamental processes. Chondrocyte mechanoreceptors have been proposed to incorporate beta1-integrins and mechanosensitive ion channels which link with key ECM, cytoskeletal and signalling proteins to maintain the chondrocyte phenotype, prevent chondrocyte apoptosis and regulate chondrocyte-specific gene expression. This review focuses on the expression and function of beta1-integrins in articular chondrocytes, its role in the unique biology of these cells and its distribution in cartilage.

  19. A review of granisetron, 5-hydroxytryptamine3 receptor antagonists, and other antiemetics.

    PubMed

    Hsu, Eric S

    2010-01-01

    Nausea and vomiting are 2 of the most upsetting adverse reactions of chemotherapy. Current guidelines propose 5-hydroxytryptamine3 (5-HT3) receptor antagonists as a pharmacologic intervention for acute and delayed nausea and vomiting [chemotherapy-induced nausea and vomiting (CINV)] associated with moderately and highly emetogenic chemotherapy. Meanwhile, both postoperative nausea and vomiting (PONV) and postdischarge nausea and vomiting are challenging situations after surgeries and procedures. Prophylactic and therapeutic combinations of antiemetics are recommended in patients at high risk of suffering from PONV and postdischarge nausea and vomiting. Granisetron (Kytril) is a selective 5-HT3 receptor antagonist that does not induce or inhibit the hepatic cytochrome P-450 system in vitro. There are also 4 other antagonists of 5-HT3 receptor (dolasetron, ondansetron, palonosetron, and tropisetron) being metabolized via the CYP2D6 and are subject to potential genetic polymorphism. The launch of a new class of antiemetics, the substance P/neurokinin1 receptor antagonists, was attributed to the scientific update on the central generator responsible for emesis and role of substance P. There has been mounting interest in exploring integrative medicine, either acupuncture or acustimulation of P6 (Nei-Kuwan), to complement the western medicine for prevention and management of nausea and vomiting. The potential application of cannabinoids, either alone or in combination with other agents of different mechanism, could contribute further to improve outcome in CINV. Implementation of future treatment guidelines for more effective management of CINV and PONV could certainly improve the efficacy and outcome of cancer and postoperative care.

  20. Slow Scan Telemedicine

    NASA Technical Reports Server (NTRS)

    1984-01-01

    Originally developed under contract for NASA by Ball Bros. Research Corporation for acquiring visual information from lunar and planetary spacecraft, system uses standard closed circuit camera connected to a device called a scan converter, which slows the stream of images to match an audio circuit, such as a telephone line. Transmitted to its destination, the image is reconverted by another scan converter and displayed on a monitor. In addition to assist scans, technique allows transmission of x-rays, nuclear scans, ultrasonic imagery, thermograms, electrocardiograms or live views of patient. Also allows conferencing and consultation among medical centers, general practitioners, specialists and disease control centers. Commercialized by Colorado Video, Inc., major employment is in business and industry for teleconferencing, cable TV news, transmission of scientific/engineering data, security, information retrieval, insurance claim adjustment, instructional programs, and remote viewing of advertising layouts, real estate, construction sites or products.

  1. USDA Gin Lab Updates

    USDA-ARS?s Scientific Manuscript database

    This presentation provides an update to ginning industry stakeholders on current research efforts ongoing at the three USDA ARS ginning laboratories in Lubbock, TX, Stoneville, MS, and Mesilla Park, NM....

  2. Control of Interference during Working Memory Updating

    ERIC Educational Resources Information Center

    Szmalec, Arnaud; Verbruggen, Frederick; Vandierendonck, Andre; Kemps, Eva

    2011-01-01

    The current study examined the nature of the processes underlying working memory updating. In 4 experiments using the n-back paradigm, the authors demonstrate that continuous updating of items in working memory prevents strong binding of those items to their contexts in working memory, and hence leads to an increased susceptibility to proactive…

  3. Census in Schools Educator Update, March 2009

    ERIC Educational Resources Information Center

    US Census Bureau, 2009

    2009-01-01

    The "Census in Schools Educator Update" is sent to educators and educational organizations periodically to keep them informed about current and upcoming census data and to provide ideas about how to use data in the classroom. This issue of the "Census in Schools Educator Update" newsletter focuses on the following topics: (1)…

  4. Striatal D(2)/D(3) receptor availability is inversely correlated with cannabis consumption in chronic marijuana users.

    PubMed

    Albrecht, Daniel S; Skosnik, Patrick D; Vollmer, Jennifer M; Brumbaugh, Margaret S; Perry, Kevin M; Mock, Bruce H; Zheng, Qi-Huang; Federici, Lauren A; Patton, Elizabeth A; Herring, Christine M; Yoder, Karmen K

    2013-02-01

    Although the incidence of cannabis abuse/dependence in Americans is rising, the neurobiology of cannabis addiction is not well understood. Imaging studies have demonstrated deficits in striatal D(2)/D(3) receptor availability in several substance-dependent populations. However, this has not been studied in currently using chronic cannabis users. The purpose of this study was to compare striatal D(2)/D(3) receptor availability between currently using chronic cannabis users and healthy controls. Eighteen right-handed males age 18-34 were studied. Ten subjects were chronic cannabis users; eight were demographically matched controls. Subjects underwent a [(11)C]raclopride (RAC) PET scan. Striatal RAC binding potential (BP(ND)) was calculated on a voxel-wise basis. Prior to scanning, urine samples were obtained from cannabis users for quantification of urine Δ-9-tetrahydrocannabinol (THC) and THC metabolites (11-nor-Δ-9-THC-9-carboxylic acid; THC-COOH and 11-hydroxy-THC;OH-THC). There were no differences in D(2)/D(3) receptor availability between cannabis users and controls. Voxel-wise analyses revealed that RAC BP(ND) values were negatively associated with both urine levels of cannabis metabolites and self-report of recent cannabis consumption. In this sample, current cannabis use was not associated with deficits in striatal D(2)/D(3) receptor availability. There was an inverse relationship between chronic cannabis use and striatal RAC BP(ND). Additional studies are needed to identify the neurochemical consequences of chronic cannabis use on the dopamine system. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  5. Structural Insights into Cargo Recognition by the Yeast PTS1 Receptor*

    PubMed Central

    Hagen, Stefanie; Drepper, Friedel; Fischer, Sven; Fodor, Krisztian; Passon, Daniel; Platta, Harald W.; Zenn, Michael; Schliebs, Wolfgang; Girzalsky, Wolfgang; Wilmanns, Matthias; Warscheid, Bettina; Erdmann, Ralf

    2015-01-01

    The peroxisomal matrix protein import is facilitated by cycling import receptors that shuttle between the cytosol and the peroxisomal membrane. The import receptor Pex5p mediates the import of proteins harboring a peroxisomal targeting signal of type I (PTS1). Purified recombinant Pex5p forms a dimeric complex with the PTS1-protein Pcs60p in vitro with a KD of 0.19 μm. To analyze the structural basis for receptor-cargo recognition, the PTS1 and adjacent amino acids of Pcs60p were systematically scanned for Pex5p binding by an in vitro site-directed photo-cross-linking approach. The cross-linked binding regions of the receptor were subsequently identified by high resolution mass spectrometry. Most cross-links were found with TPR6, TPR7, as well as the 7C-loop of Pex5p. Surface plasmon resonance analysis revealed a bivalent interaction mode for Pex5p and Pcs60p. Interestingly, Pcs60p lacking its C-terminal tripeptide sequence was efficiently cross-linked to the same regions of Pex5p. The KD value of the interaction of truncated Pcs60p and Pex5p was in the range of 7.7 μm. Isothermal titration calorimetry and surface plasmon resonance measurements revealed a monovalent binding mode for the interaction of Pex5p and Pcs60p lacking the PTS1. Our data indicate that Pcs60p contains a second contact site for its receptor Pex5p, beyond the C-terminal tripeptide. The physiological relevance of the ancillary binding region was supported by in vivo import studies. The bivalent binding mode might be explained by a two-step concept as follows: first, cargo recognition and initial tethering by the PTS1-receptor Pex5p; second, lock-in of receptor and cargo. PMID:26359497

  6. Situation Model Updating in Young and Older Adults: Global versus Incremental Mechanisms

    PubMed Central

    Bailey, Heather R.; Zacks, Jeffrey M.

    2015-01-01

    Readers construct mental models of situations described by text. Activity in narrative text is dynamic, so readers must frequently update their situation models when dimensions of the situation change. Updating can be incremental, such that a change leads to updating just the dimension that changed, or global, such that the entire model is updated. Here, we asked whether older and young adults make differential use of incremental and global updating. Participants read narratives containing changes in characters and spatial location and responded to recognition probes throughout the texts. Responses were slower when probes followed a change, suggesting that situation models were updated at changes. When either dimension changed, responses to probes for both dimensions were slowed; this provides evidence for global updating. Moreover, older adults showed stronger evidence of global updating than did young adults. One possibility is that older adults perform more global updating to offset reduced ability to manipulate information in working memory. PMID:25938248

  7. Re-scan confocal microscopy: scanning twice for better resolution

    PubMed Central

    De Luca, Giulia M.R.; Breedijk, Ronald M.P.; Brandt, Rick A.J.; Zeelenberg, Christiaan H.C.; de Jong, Babette E.; Timmermans, Wendy; Azar, Leila Nahidi; Hoebe, Ron A.; Stallinga, Sjoerd; Manders, Erik M.M.

    2013-01-01

    We present a new super-resolution technique, Re-scan Confocal Microscopy (RCM), based on standard confocal microscopy extended with an optical (re-scanning) unit that projects the image directly on a CCD-camera. This new microscope has improved lateral resolution and strongly improved sensitivity while maintaining the sectioning capability of a standard confocal microscope. This simple technology is typically useful for biological applications where the combination high-resolution and high-sensitivity is required. PMID:24298422

  8. Re-scan confocal microscopy: scanning twice for better resolution.

    PubMed

    De Luca, Giulia M R; Breedijk, Ronald M P; Brandt, Rick A J; Zeelenberg, Christiaan H C; de Jong, Babette E; Timmermans, Wendy; Azar, Leila Nahidi; Hoebe, Ron A; Stallinga, Sjoerd; Manders, Erik M M

    2013-01-01

    We present a new super-resolution technique, Re-scan Confocal Microscopy (RCM), based on standard confocal microscopy extended with an optical (re-scanning) unit that projects the image directly on a CCD-camera. This new microscope has improved lateral resolution and strongly improved sensitivity while maintaining the sectioning capability of a standard confocal microscope. This simple technology is typically useful for biological applications where the combination high-resolution and high-sensitivity is required.

  9. Advanced scanning probe lithography.

    PubMed

    Garcia, Ricardo; Knoll, Armin W; Riedo, Elisa

    2014-08-01

    The nanoscale control afforded by scanning probe microscopes has prompted the development of a wide variety of scanning-probe-based patterning methods. Some of these methods have demonstrated a high degree of robustness and patterning capabilities that are unmatched by other lithographic techniques. However, the limited throughput of scanning probe lithography has prevented its exploitation in technological applications. Here, we review the fundamentals of scanning probe lithography and its use in materials science and nanotechnology. We focus on robust methods, such as those based on thermal effects, chemical reactions and voltage-induced processes, that demonstrate a potential for applications.

  10. Estrogen-related receptor β (ERRβ) – renaissance receptor or receptor renaissance?

    PubMed Central

    Divekar, Shailaja D.; Tiek, Deanna M.; Fernandez, Aileen; Riggins, Rebecca B.

    2016-01-01

    Estrogen-related receptors (ERRs) are founding members of the orphan nuclear receptor (ONR) subgroup of the nuclear receptor superfamily. Twenty-seven years of study have yet to identify cognate ligands for the ERRs, though they have firmly placed ERRα and ERRγ at the intersection of cellular metabolism and oncogenesis. The pace of discovery for novel functions of ERRβ, however, has until recently been somewhat slower than that of its family members. ERRβ has also been largely ignored in summaries and perspectives of the ONR literature. Here, we provide an overview of established and emerging knowledge of ERRβ in mouse, man, and other species, highlighting unique aspects of ERRβ biology that set it apart from the other two estrogen-related receptors, with a focus on the impact of alternative splicing on the structure and function of this receptor. PMID:27507929

  11. Defining the Cubature Changes of Historic St. Kinga Chamber in Bochnia Salt Mine, Using Laser Scanning Technology

    NASA Astrophysics Data System (ADS)

    Szafarczyk, Anna; Gawałkiewicz, Rafał

    2018-03-01

    In Poland, there are many mining enterprises, of historic character registered in the UNESCO World Heritage List. One of the oldest mining enterprises in Poland is the Salt Mine in Bochnia. The processes inside the rock mass require that surveying services carry out regular geometric control of the cavities. A particular attention should be paid (due to its sacral function) on St. Kinga Chamber, located 195 metres below the surface, on the mine level "August". So far measurement technologies have been connected with the studies on changes in the geometry of cavities and based on linear bases used to measure convergence. This only provides discrete information (in a point) and not always presents a real state of deformation. In the scanning method, in practice a three dimension image of changes (structural deformations) is obtained, impossible to determine with the application of measurement methods, applied to measure the value of linear convergence (the method with a limited number of bases). Laser scanning, apart from determining the value of volume convergence, gives also the possibility of the visualization of 3D cavern. Moreover, it provides direct information to update mining numerical maps and make it possible to generate various cross-sections through the cavern. The authors analysed the possibility of the application of laser scanning (scanner Faro Focus 3D), as a modern tool allowing the measuring of the value of volume convergence.

  12. Indoor Spatial Updating with Reduced Visual Information

    PubMed Central

    Legge, Gordon E.; Gage, Rachel; Baek, Yihwa; Bochsler, Tiana M.

    2016-01-01

    Purpose Spatial updating refers to the ability to keep track of position and orientation while moving through an environment. People with impaired vision may be less accurate in spatial updating with adverse consequences for indoor navigation. In this study, we asked how artificial restrictions on visual acuity and field size affect spatial updating, and also judgments of the size of rooms. Methods Normally sighted young adults were tested with artificial restriction of acuity in Mild Blur (Snellen 20/135) and Severe Blur (Snellen 20/900) conditions, and a Narrow Field (8°) condition. The subjects estimated the dimensions of seven rectangular rooms with and without these visual restrictions. They were also guided along three-segment paths in the rooms. At the end of each path, they were asked to estimate the distance and direction to the starting location. In Experiment 1, the subjects walked along the path. In Experiment 2, they were pushed in a wheelchair to determine if reduced proprioceptive input would result in poorer spatial updating. Results With unrestricted vision, mean Weber fractions for room-size estimates were near 20%. Severe Blur but not Mild Blur yielded larger errors in room-size judgments. The Narrow Field was associated with increased error, but less than with Severe Blur. There was no effect of visual restriction on estimates of distance back to the starting location, and only Severe Blur yielded larger errors in the direction estimates. Contrary to expectation, the wheelchair subjects did not exhibit poorer updating performance than the walking subjects, nor did they show greater dependence on visual condition. Discussion If our results generalize to people with low vision, severe deficits in acuity or field will adversely affect the ability to judge the size of indoor spaces, but updating of position and orientation may be less affected by visual impairment. PMID:26943674

  13. Indoor Spatial Updating with Reduced Visual Information.

    PubMed

    Legge, Gordon E; Gage, Rachel; Baek, Yihwa; Bochsler, Tiana M

    2016-01-01

    Spatial updating refers to the ability to keep track of position and orientation while moving through an environment. People with impaired vision may be less accurate in spatial updating with adverse consequences for indoor navigation. In this study, we asked how artificial restrictions on visual acuity and field size affect spatial updating, and also judgments of the size of rooms. Normally sighted young adults were tested with artificial restriction of acuity in Mild Blur (Snellen 20/135) and Severe Blur (Snellen 20/900) conditions, and a Narrow Field (8°) condition. The subjects estimated the dimensions of seven rectangular rooms with and without these visual restrictions. They were also guided along three-segment paths in the rooms. At the end of each path, they were asked to estimate the distance and direction to the starting location. In Experiment 1, the subjects walked along the path. In Experiment 2, they were pushed in a wheelchair to determine if reduced proprioceptive input would result in poorer spatial updating. With unrestricted vision, mean Weber fractions for room-size estimates were near 20%. Severe Blur but not Mild Blur yielded larger errors in room-size judgments. The Narrow Field was associated with increased error, but less than with Severe Blur. There was no effect of visual restriction on estimates of distance back to the starting location, and only Severe Blur yielded larger errors in the direction estimates. Contrary to expectation, the wheelchair subjects did not exhibit poorer updating performance than the walking subjects, nor did they show greater dependence on visual condition. If our results generalize to people with low vision, severe deficits in acuity or field will adversely affect the ability to judge the size of indoor spaces, but updating of position and orientation may be less affected by visual impairment.

  14. Spatial Updating and the Maintenance of Visual Constancy

    PubMed Central

    Klier, Eliana M.; Angelaki, Dora E.

    2008-01-01

    Spatial updating is the means by which we keep track of the locations of objects in space even as we move. Four decades of research have shown that humans and non-human primates can take the amplitude and direction of intervening movements into account, including saccades (both head-fixed and head-free), pursuit, whole-body rotations and translations. At the neuronal level, spatial updating is thought to be maintained by receptive field locations that shift with changes in gaze and evidence for such shifts have been shown in several cortical areas. These regions receive information about the intervening movement from several sources including motor efference copies when a voluntary movement is made and vestibular/somatosensory signals when the body is in motion. Many of these updating signals arise from brainstem regions that monitor our ongoing movements and subsequently transmit this information to the cortex via pathways that likely include the thalamus. Several issues of debate include (1) the relative contribution of extra-retinal sensory and efference copy signals to spatial updating, (2) the source of an updating signal for real life, three-dimensional motion that cannot arise from brain areas encoding only two-dimensional commands, and (3) the reference frames used by the brain to integrate updating signals from various sources. This review highlights the relevant spatial updating studies and provides a summary of the field today. We find that spatial constancy is maintained by a highly evolved neural mechanism that keeps track of our movements, transmits this information to relevant brain regions, and then uses this information to change the way in which single neurons respond. In this way, we are able to keep track of relevant objects in the outside world and interact with them in meaningful ways. PMID:18786618

  15. America’s Children and the Environment Update Listserv

    EPA Pesticide Factsheets

    EPA maintains a distribution list to announce updates to the America’s Children and the Environment website. Whenever new or updated content is added to the site, subscribers to the list will receive a notification by e-mail.

  16. Community Update, 1999.

    ERIC Educational Resources Information Center

    Anderson, Julie, Ed.

    1999-01-01

    This document consists of nine issues (covering January through December 1999) of the newsletter "Community Update," containing articles on community and family involvement in education. Article topics include: new programs to help students prepare for college early; Vice President Al Gore announced the first-ever national Hispanic Education…

  17. "Southwest Strategy" update

    Treesearch

    Steve Kluge

    1999-01-01

    The Southwest Strategy is an effort by federal agencies to work with each other, the public, and tribal, state, and local agencies to maintain and restore the cultural, economic, and environmental quality of life in Arizona and New Mexico. This update explains the strategy and its progress to date.

  18. Electricity Monthly Update

    EIA Publications

    2017-01-01

    Provides analysis and highlights of the data included in the Electric Power Monthly (EPM) publication and presents tables of electricity generation, fuel consumption for generation, fossil fuel stocks, and average retail sales and prices of electricity. The Electricity Monthly Update is published at the same time as the EPM.

  19. Constellation Program Update

    NASA Image and Video Library

    2006-06-04

    Jeff Hanley, Constellation Program Manager, right, listens to a question during a NASA Update outlining responsibilities of the NASA centers associated with the Constellation Program for robotic and human Moon and Mars exploration on Wednesday, June 5, 2006, at NASA Headquarters in Washington. Photo Credit: (NASA/Bill Ingalls)

  20. Community Update, 2001.

    ERIC Educational Resources Information Center

    Ashby, Nicole, Ed.

    2001-01-01

    This document consists of 10 issues (covering January through December 2000) of the newsletter, "Community Update," which features articles on community and family involvement in education. In addition to the articles, each issue (except the Special Issue) includes a preview of the month's Satellite Town Meeting; events and information…

  1. CGRP Receptor Biology: Is There More Than One Receptor?

    PubMed

    Hay, Debbie L

    2018-05-25

    Calcitonin gene-related peptide (CGRP) has many reported pharmacological actions. Can a single receptor explain all of these? This chapter outlines the molecular nature of reported CGRP binding proteins and their pharmacology. Consideration of whether CGRP has only one or has more receptors is important because of the key role that this peptide plays in migraine. It is widely thought that the calcitonin receptor-like receptor together with receptor activity-modifying protein 1 (RAMP1) is the only relevant receptor for CGRP. However, some closely related receptors also have high affinity for CGRP and it is still plausible that these play a role in CGRP biology, and in migraine. The calcitonin receptor/RAMP1 complex, which is currently called the AMY 1 receptor, seems to be the most likely candidate but more investigation is needed to determine its role.

  2. An efficient scan diagnosis methodology according to scan failure mode for yield enhancement

    NASA Astrophysics Data System (ADS)

    Kim, Jung-Tae; Seo, Nam-Sik; Oh, Ghil-Geun; Kim, Dae-Gue; Lee, Kyu-Taek; Choi, Chi-Young; Kim, InSoo; Min, Hyoung Bok

    2008-12-01

    Yield has always been a driving consideration during fabrication of modern semiconductor industry. Statistically, the largest portion of wafer yield loss is defective scan failure. This paper presents efficient failure analysis methods for initial yield ramp up and ongoing product with scan diagnosis. Result of our analysis shows that more than 60% of the scan failure dies fall into the category of shift mode in the very deep submicron (VDSM) devices. However, localization of scan shift mode failure is very difficult in comparison to capture mode failure because it is caused by the malfunction of scan chain. Addressing the biggest challenge, we propose the most suitable analysis method according to scan failure mode (capture / shift) for yield enhancement. In the event of capture failure mode, this paper describes the method that integrates scan diagnosis flow and backside probing technology to obtain more accurate candidates. We also describe several unique techniques, such as bulk back-grinding solution, efficient backside probing and signal analysis method. Lastly, we introduce blocked chain analysis algorithm for efficient analysis of shift failure mode. In this paper, we contribute to enhancement of the yield as a result of the combination of two methods. We confirm the failure candidates with physical failure analysis (PFA) method. The direct feedback of the defective visualization is useful to mass-produce devices in a shorter time. The experimental data on mass products show that our method produces average reduction by 13.7% in defective SCAN & SRAM-BIST failure rates and by 18.2% in wafer yield rates.

  3. NASA Update

    NASA Image and Video Library

    2009-07-20

    NASA Administrator Charles F. Bolden Jr. is seen through a television camera monitor during his first NASA Update,Tuesday, July 21, 2009, at NASA Headquarters in Washington. Bolden, NASA's 12th Administrator, was joined by Deputy Administrator Lori Garver where they took the time to introduce themselves and outline their vision for the agency going forward. No questions were taken during the session. Photo Credit: (NASA/Bill Ingalls)

  4. NASA Update

    NASA Image and Video Library

    2009-07-20

    NASA Administrator Charles F. Bolden Jr. is seen on a television camera monitor while speaking at his first NASA Update,Tuesday, July 21, 2009, at NASA Headquarters in Washington. Bolden, NASA's 12th Administrator, was joined by Deputy Administrator Lori Garver where they took the time to introduce themselves and outline their vision for the agency going forward. No questions were taken during the session. Photo Credit: (NASA/Bill Ingalls)

  5. Asteroid Redirect Mission Update

    NASA Image and Video Library

    2017-12-08

    Dr. Holdren (left), Administrator Bolden (center) and Dr. Michele Gates (right) discuss the ARM mission during a live NASA TV briefing. Behind them is a mockup of robotic capture module for the Asteroid Redirect Mission. More info: Asteroid Redirect Mission Update – On Sept. 14, 2016, NASA provided an update on the Asteroid Redirect Mission (ARM) and how it contributes to the agency’s journey to Mars and protection of Earth. The presentation took place in the Robotic Operations Center at NASA’s Goddard Space Flight Center in Greenbelt, Maryland. Assistant to the President for Science and Technology Dr. John P. Holdren, NASA Administrator Charles Bolden and NASA’s ARM Program Director, Dr. Michele Gates discussed the latest update regarding the mission. They explained the mission’s scientific and technological benefits and how ARM will demonstrate technology for defending Earth from potentially hazardous asteroids. The briefing aired live on NASA TV and the agency’s website. For more information about ARM go to www.nasa.gov/arm. Credit: NASA/Goddard/Debbie Mccallum NASA image use policy. NASA Goddard Space Flight Center enables NASA’s mission through four scientific endeavors: Earth Science, Heliophysics, Solar System Exploration, and Astrophysics. Goddard plays a leading role in NASA’s accomplishments by contributing compelling scientific knowledge to advance the Agency’s mission. Follow us on Twitter Like us on Facebook Find us on Instagram

  6. Asteroid Redirect Mission Update

    NASA Image and Video Library

    2017-12-08

    Dr. Holdren (left), Administrator Bolden (center) and Dr. Michele Gates (right) discuss the ARM mission during a live NASA TV briefing. Behind them is a mockup of robotic capture module for the Asteroid Redirect Mission. More info: Asteroid Redirect Mission Update – On Sept. 14, 2016, NASA provided an update on the Asteroid Redirect Mission (ARM) and how it contributes to the agency’s journey to Mars and protection of Earth. The presentation took place in the Robotic Operations Center at NASA’s Goddard Space Flight Center in Greenbelt, Maryland. Assistant to the President for Science and Technology Dr. John P. Holdren, NASA Administrator Charles Bolden and NASA’s ARM Program Director, Dr. Michele Gates discussed the latest update regarding the mission. They explained the mission’s scientific and technological benefits and how ARM will demonstrate technology for defending Earth from potentially hazardous asteroids. The briefing aired live on NASA TV and the agency’s website. For more information about ARM go to www.nasa.gov/arm. Credit: NASA/Goddard/Peter Sooy NASA image use policy. NASA Goddard Space Flight Center enables NASA’s mission through four scientific endeavors: Earth Science, Heliophysics, Solar System Exploration, and Astrophysics. Goddard plays a leading role in NASA’s accomplishments by contributing compelling scientific knowledge to advance the Agency’s mission. Follow us on Twitter Like us on Facebook Find us on Instagram

  7. PrionScan: an online database of predicted prion domains in complete proteomes.

    PubMed

    Espinosa Angarica, Vladimir; Angulo, Alfonso; Giner, Arturo; Losilla, Guillermo; Ventura, Salvador; Sancho, Javier

    2014-02-05

    Prions are a particular type of amyloids related to a large variety of important processes in cells, but also responsible for serious diseases in mammals and humans. The number of experimentally characterized prions is still low and corresponds to a handful of examples in microorganisms and mammals. Prion aggregation is mediated by specific protein domains with a remarkable compositional bias towards glutamine/asparagine and against charged residues and prolines. These compositional features have been used to predict new prion proteins in the genomes of different organisms. Despite these efforts, there are only a few available data sources containing prion predictions at a genomic scale. Here we present PrionScan, a new database of predicted prion-like domains in complete proteomes. We have previously developed a predictive methodology to identify and score prionogenic stretches in protein sequences. In the present work, we exploit this approach to scan all the protein sequences in public databases and compile a repository containing relevant information of proteins bearing prion-like domains. The database is updated regularly alongside UniprotKB and in its present version contains approximately 28000 predictions in proteins from different functional categories in more than 3200 organisms from all the taxonomic subdivisions. PrionScan can be used in two different ways: database query and analysis of protein sequences submitted by the users. In the first mode, simple queries allow to retrieve a detailed description of the properties of a defined protein. Queries can also be combined to generate more complex and specific searching patterns. In the second mode, users can submit and analyze their own sequences. It is expected that this database would provide relevant insights on prion functions and regulation from a genome-wide perspective, allowing researches performing cross-species prion biology studies. Our database might also be useful for guiding experimentalists

  8. Census in Schools Educator Update, June 2009

    ERIC Educational Resources Information Center

    US Census Bureau, 2009

    2009-01-01

    The "Census in Schools Educator Update" is sent to educators and educational organizations periodically to keep them informed about current and upcoming census data and to provide ideas about how to use data in the classroom. This issue of the "Census in Schools Educator Update" newsletter focuses on the following topics: (1) 2010 Census; (2)…

  9. Environmental Scanning Report.

    ERIC Educational Resources Information Center

    Truckee Meadows Community Coll., Sparks, NV.

    This report describes Truckee Meadows Community College's (Nevada) environmental scanning process and results. The college decided that environmental scanning and forecasting techniques should be used to plan for both short-term and long-term external factors that impact programs, enrollment, and budgets. Strategic goals include: (1) keeping pace…

  10. Norepinephrine Activates Dopamine D4 Receptors in the Rat Lateral Habenula

    PubMed Central

    Root, David H.; Hoffman, Alexander F.; Good, Cameron H.; Zhang, Shiliang; Gigante, Eduardo

    2015-01-01

    The lateral habenula (LHb) is involved in reward and aversion and is reciprocally connected with dopamine (DA)-containing brain regions, including the ventral tegmental area (VTA). We used a multidisciplinary approach to examine the properties of DA afferents to the LHb in the rat. We find that >90% of VTA tyrosine hydroxylase (TH) neurons projecting to the LHb lack vesicular monoamine transporter 2 (VMAT2) mRNA, and there is little coexpression of TH and VMAT2 protein in this mesohabenular pathway. Consistent with this, electrical stimulation of LHb did not evoke DA-like signals, assessed with fast-scan cyclic voltammetry. However, electrophysiological currents that were inhibited by L741,742, a DA-D4-receptor antagonist, were observed in LHb neurons when DA uptake or degradation was blocked. To prevent DA activation of D4 receptors, we repeated this experiment in LHb slices from DA-depleted rats. However, this did not disrupt D4 receptor activation initiated by the dopamine transporter inhibitor, GBR12935. As the LHb is also targeted by noradrenergic afferents, we examined whether GBR12935 activation of DA-D4 receptors occurred in slices depleted of norepinephrine (NE). Unlike DA, NE depletion prevented the activation of DA-D4 receptors. Moreover, direct application of NE elicited currents in LHb neurons that were blocked by L741,742, and GBR12935 was found to be a more effective blocker of NE uptake than the NE-selective transport inhibitor nisoxetine. These findings demonstrate that NE is released in the rat LHb under basal conditions and that it activates DA-D4 receptors. Therefore, NE may be an important regulator of LHb function. PMID:25716845

  11. Glycoprotein hormone receptors: determinants in leucine-rich repeats responsible for ligand specificity

    PubMed Central

    Smits, Guillaume; Campillo, Mercedes; Govaerts, Cédric; Janssens, Véronique; Richter, Christine; Vassart, Gilbert; Pardo, Leonardo; Costagliola, Sabine

    2003-01-01

    Glycoprotein hormone receptors [thyrotropin (TSHr), luteinizing hormone/chorionic gonadotropin (LH/CGr), follicle stimulating hormone (FSHr)] are rhodopsin-like G protein-coupled receptors with a large extracellular N-terminal portion responsible for hormone recognition and binding. In structural models, this ectodomain is composed of two cysteine clusters flanking nine leucine-rich repeats (LRRs). The LRRs form a succession of β-strands and α-helices organized into a horseshoe-shaped structure. It has been proposed that glycoprotein hormones interact with residues of the β-strands making the concave surface of the horseshoe. Gain-of-function homology scanning of the β-strands of glycoprotein hormone receptors allowed identification of the critical residues responsible for the specificity towards human chorionic gonadotropin (hCG). Substitution of eight or two residues of the LH/CGr into the TSHr or FSHr, respectively, resulted in constructs displaying almost the same affinity and sensitivity for hCG as wild-type LH/CGr. Molecular dynamics simulations and additional site-directed mutagenesis provided a structural rationale for the evolution of binding specificity in this duplicated gene family. PMID:12773385

  12. Pituitary gigantism: update on molecular biology and management.

    PubMed

    Lodish, Maya B; Trivellin, Giampaolo; Stratakis, Constantine A

    2016-02-01

    To provide an update on the mechanisms leading to pituitary gigantism, as well as to familiarize the practitioner with the implication of these genetic findings on treatment decisions. Prior studies have identified gigantism as a feature of a number of monogenic disorders, including mutations in the aryl hydrocarbon receptor interacting protein gene, multiple endocrine neoplasia types 1 and 4, McCune Albright syndrome, Carney complex, and the paraganglioma, pheochromocytoma, and pituitary adenoma association because of succinate dehydrogenase defects. We recently described a previously uncharacterized form of early-onset pediatric gigantism caused by microduplications on chromosome Xq26.3 and we termed it X-LAG (X-linked acrogigantism). The age of onset of increased growth in X-LAG is significantly younger than other pituitary gigantism cases, and control of growth hormone excess is particularly challenging. Knowledge of the molecular defects that underlie pituitary tumorigenesis is crucial for patient care as they guide early intervention, screening for associated conditions, genetic counseling, surgical approach, and choice of medical management. Recently described microduplications of Xq26.3 account for more than 80% of the cases of early-onset pediatric gigantism. Early recognition of X-LAG may improve outcomes, as successful control of growth hormone excess requires extensive anterior pituitary resection and are difficult to manage with medical therapy alone.

  13. Insulin receptors

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Kahn, C.R.; Harrison, L.C.

    1988-01-01

    This book contains the procedure in insulin receptors. Part B: Clinical assessment, biological responses, and comparison to the IGF-1 receptor. Topics covered include: Insulin and IGF-1 receptors, Clinical assessment of receptor functions, and Biological responses.

  14. Constellation Program Update

    NASA Image and Video Library

    2006-06-04

    NASA Administrator Michael Griffin addresses NASA employees and members of the media about the responsibilities of the NASA centers associated with the Constellation Program for robotic and human Moon and Mars exploration during a NASA Update on Wednesday, June 5, 2006, at NASA Headquarters in Washington. Photo Credit: (NASA/Bill Ingalls)

  15. Constellation Program Update

    NASA Image and Video Library

    2006-06-04

    Dean Acosta, NASA Deputy Assistant Administrator and Press Secretary, left, moderates a NASA Update with NASA Administrator Michael Griffin, Scott J. Horowitz, NASA Associate Administrator for Exploration Systems and Jeff Hanley, Constellation Program Manager, right, on Wednesday, June 5, 2006, at NASA Headquarters in Washington. Photo Credit: (NASA/Bill Ingalls)

  16. Right ventricular sarcoidosis: is it time for updated diagnostic criteria?

    PubMed

    Vakil, Kairav; Minami, Elina; Fishbein, Daniel P

    2014-04-01

    A 55-year-old woman with a history of complete heart block, atrial flutter, and progressive right ventricular failure was referred to our tertiary care center to be evaluated for cardiac transplantation. The patient's clinical course included worsening right ventricular dysfunction for 3 years before the current evaluation. Our clinical findings raised concerns about arrhythmogenic right ventricular cardiomyopathy. Noninvasive imaging, including a positron emission tomographic scan, did not reveal obvious myocardial pathologic conditions. Given the end-stage nature of the patient's right ventricular failure and her dependence on inotropic agents, she underwent urgent listing and subsequent heart transplantation. Pathologic examination of the explanted heart revealed isolated right ventricular sarcoidosis with replacement fibrosis. Biopsy samples of the cardiac allograft 6 months after transplantation showed no recurrence of sarcoidosis. This atypical presentation of isolated cardiac sarcoidosis posed a considerable diagnostic challenge. In addition to discussing the patient's case, we review the relevant medical literature and discuss the need for updated differential diagnostic criteria for end-stage right ventricular failure that mimics arrhythmogenic right ventricular cardiomyopathy.

  17. Environmental Scanning and the Information Manager.

    ERIC Educational Resources Information Center

    Newsome, James; McInerney, Claire

    1990-01-01

    Discusses nine components of an environmental scanning model: selecting the scanning team; selecting resources to scan; choosing criteria for scanning; scanning the resources; identifying signals of new issues; selecting key events/issues; monitoring and analyzing events/issues; disseminating information; and deciding on appropriate organizational…

  18. Multiline radar scan

    NASA Technical Reports Server (NTRS)

    Levinson, S.

    1977-01-01

    Scanning scheme is more efficient than conventional scanning. Originally designed for optical radar in space vehicles, scheme may also find uses in site-surveillance security systems and in other industrial applications. It should be particularly useful when system must run on battery energy, as would be case in power outages.

  19. Role of dopamine D2 receptors in optimizing choice strategy in a dynamic and uncertain environment

    PubMed Central

    Kwak, Shinae; Huh, Namjung; Seo, Ji-Seon; Lee, Jung-Eun; Han, Pyung-Lim; Jung, Min W.

    2014-01-01

    In order to investigate roles of dopamine receptor subtypes in reward-based learning, we examined choice behavior of dopamine D1 and D2 receptor-knockout (D1R-KO and D2R-KO, respectively) mice in an instrumental learning task with progressively increasing reversal frequency and a dynamic two-armed bandit task. Performance of D2R-KO mice was progressively impaired in the former as the frequency of reversal increased and profoundly impaired in the latter even with prolonged training, whereas D1R-KO mice showed relatively minor performance deficits. Choice behavior in the dynamic two-armed bandit task was well explained by a hybrid model including win-stay-lose-switch and reinforcement learning terms. A model-based analysis revealed increased win-stay, but impaired value updating and decreased value-dependent action selection in D2R-KO mice, which were detrimental to maximizing rewards in the dynamic two-armed bandit task. These results suggest an important role of dopamine D2 receptors in learning from past choice outcomes for rapid adjustment of choice behavior in a dynamic and uncertain environment. PMID:25389395

  20. 49 CFR 194.121 - Response plan review and update procedures.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 3 2011-10-01 2011-10-01 false Response plan review and update procedures. 194... SAFETY RESPONSE PLANS FOR ONSHORE OIL PIPELINES Response Plans § 194.121 Response plan review and update procedures. (a) Each operator shall update its response plan to address new or different operating conditions...

  1. 49 CFR 194.121 - Response plan review and update procedures.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 3 2013-10-01 2013-10-01 false Response plan review and update procedures. 194... SAFETY RESPONSE PLANS FOR ONSHORE OIL PIPELINES Response Plans § 194.121 Response plan review and update procedures. (a) Each operator shall update its response plan to address new or different operating conditions...

  2. 49 CFR 194.121 - Response plan review and update procedures.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 3 2014-10-01 2014-10-01 false Response plan review and update procedures. 194... SAFETY RESPONSE PLANS FOR ONSHORE OIL PIPELINES Response Plans § 194.121 Response plan review and update procedures. (a) Each operator shall update its response plan to address new or different operating conditions...

  3. 49 CFR 194.121 - Response plan review and update procedures.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 3 2012-10-01 2012-10-01 false Response plan review and update procedures. 194... SAFETY RESPONSE PLANS FOR ONSHORE OIL PIPELINES Response Plans § 194.121 Response plan review and update procedures. (a) Each operator shall update its response plan to address new or different operating conditions...

  4. 49 CFR 194.121 - Response plan review and update procedures.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 3 2010-10-01 2010-10-01 false Response plan review and update procedures. 194... SAFETY RESPONSE PLANS FOR ONSHORE OIL PIPELINES Response Plans § 194.121 Response plan review and update procedures. (a) Each operator shall update its response plan to address new or different operating conditions...

  5. Alternative Fuels Data Center: Status Update: Requirements Have Not Changed

    Science.gov Websites

    Fuels Data Center: Status Update: Requirements Have Not Changed (June 2008) on Facebook Tweet about Alternative Fuels Data Center: Status Update: Requirements Have Not Changed (June 2008) on Twitter Bookmark Alternative Fuels Data Center: Status Update: Requirements Have Not Changed (June 2008) on Google Bookmark

  6. State and Local Governments Email Updates | State, Local, and Tribal

    Science.gov Websites

    Governments | NREL Local Governments Email Updates State and Local Governments Email Updates : NREL does not share its email lists with other organizations or companies. Subscribe To subscribe for email updates, please provide and submit the following information. * indicates required Full Name

  7. Statistical and perceptual updating: correlated impairments in right brain injury.

    PubMed

    Stöttinger, Elisabeth; Filipowicz, Alex; Marandi, Elahe; Quehl, Nadine; Danckert, James; Anderson, Britt

    2014-06-01

    It has been hypothesized that many of the cognitive impairments commonly seen after right brain damage (RBD) can be characterized as a failure to build or update mental models. We (Danckert et al. in Neglect as a disorder of representational updating. NOVA Open Access, New York, 2012a; Cereb Cortex 22:2745-2760, 2012b) were the first to directly assess the association between RBD and updating and found that RBD patients were unable to exploit a strongly biased play strategy in their opponent in the children's game rock, paper, scissors. Given that this game required many other cognitive capacities (i.e., working memory, sustained attention, reward processing), RBD patients could have failed this task for various reasons other than a failure to update. To assess the generality of updating deficits after RBD, we had RBD, left brain-damaged (LBD) patients and healthy controls (HCs) describe line drawings that evolved gradually from one figure (e.g., rabbit) to another (e.g., duck) in addition to the RPS updating task. RBD patients took significantly longer to alter their perceptual report from the initial object to the final object than did LBD patients and HCs. Although both patient groups performed poorly on the RPS task, only the RBD patients showed a significant correlation between the two, very different, updating tasks. We suggest these data indicate a general deficiency in the ability to update mental representations following RBD.

  8. Infrared Scanning

    NASA Technical Reports Server (NTRS)

    1987-01-01

    United Scanning Technologies, Inc.'s Infrared thermography is a relatively new noncontact, nondestructive inspection and testing tool which makes temperatures visible to the human eye. Infrared scanning devices produce images that show, by color or black and white shading differences, heat losses through damaged or inadequately insulated walls or roofs. The MISS Aeroscan services are designed to take the guesswork out of industrial roof maintenance and provide companies big savings by identifying the location of moisture damage from roof leaks, effectively targeting maintenance attention.

  9. 78 FR 26244 - Updating of Employer Identification Numbers

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-05-06

    ... (including updated application information regarding the name and taxpayer identifying number of the... require these persons to update application information regarding the name and taxpayer identifying number..., Application for Employer Identification Number, requires entities to disclose the name of the EIN applicant's...

  10. Retinoic Acid-Related Orphan Receptors (RORs): Regulatory Functions in Immunity, Development, Circadian Rhythm, and Metabolism

    PubMed Central

    Cook, Donald N.; Kang, Hong Soon; Jetten, Anton M.

    2015-01-01

    In this overview, we provide an update on recent progress made in understanding the mechanisms of action, physiological functions, and roles in disease of retinoic acid related orphan receptors (RORs). We are particularly focusing on their roles in the regulation of adaptive and innate immunity, brain function, retinal development, cancer, glucose and lipid metabolism, circadian rhythm, metabolic and inflammatory diseases and neuropsychiatric disorders. We also summarize the current status of ROR agonists and inverse agonists, including their regulation of ROR activity and their therapeutic potential for management of various diseases in which RORs have been implicated. PMID:26878025

  11. The distance effect in numerical memory-updating tasks.

    PubMed

    Lendínez, Cristina; Pelegrina, Santiago; Lechuga, Teresa

    2011-05-01

    Two experiments examined the role of numerical distance in updating numerical information in working memory. In the first experiment, participants had to memorize a new number only when it was smaller than a previously memorized number. In the second experiment, updating was based on an external signal, which removed the need to perform any numerical comparison. In both experiments, distance between the memorized number and the new one was manipulated. The results showed that smaller distances between the new and the old information led to shorter updating times. This graded facilitation suggests that the process by which information is substituted in the focus of attention involves maintaining the shared features between the new and the old number activated and selecting other new features to be activated. Thus, the updating cost may be related to amount of new features to be activated in the focus of attention.

  12. Codification of scan path parameters and development of perimeter scan strategies for 3D bowl-shaped laser forming

    NASA Astrophysics Data System (ADS)

    Tavakoli, A.; Naeini, H. Moslemi; Roohi, Amir H.; Gollo, M. Hoseinpour; Shahabad, Sh. Imani

    2018-01-01

    In the 3D laser forming process, developing an appropriate laser scan pattern for producing specimens with high quality and uniformity is critical. This study presents certain principles for developing scan paths. Seven scan path parameters are considered, including: (1) combined linear or curved path; (2) type of combined linear path; (3) order of scan sequences; (4) the position of the start point in each scan; (5) continuous or discontinuous scan path; (6) direction of scan path; and (7) angular arrangement of combined linear scan paths. Regarding these path parameters, ten combined linear scan patterns are presented. Numerical simulations show continuous hexagonal, scan pattern, scanning from outer to inner path, is the optimized. In addition, it is observed the position of the start point and the angular arrangement of scan paths is the most effective path parameters. Also, further experimentations show four sequences due to creat symmetric condition enhance the height of the bowl-shaped products and uniformity. Finally, the optimized hexagonal pattern was compared with the similar circular one. In the hexagonal scan path, distortion value and standard deviation rather to edge height of formed specimen is very low, and the edge height despite of decreasing length of scan path increases significantly compared to the circular scan path. As a result, four-sequence hexagonal scan pattern is proposed as the optimized perimeter scan path to produce bowl-shaped product.

  13. Alternative Fuels Data Center: Status Update: E85 Dispenser System

    Science.gov Websites

    Alternative Fuels Data Center: Status Update: E85 Dispenser System Certified (June 2010) on Facebook Tweet about Alternative Fuels Data Center: Status Update: E85 Dispenser System Certified (June 2010) on Twitter Bookmark Alternative Fuels Data Center: Status Update: E85 Dispenser System Certified (June 2010

  14. Environmental Regulatory Update Table, January/February 1995

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Houlberg, L.M.; Hawkins, G.T.; Bock, R.E.

    1995-03-01

    The Environmental Regulatory Update Table provides information on regulatory initiatives impacting environmental, health, and safety management responsibilities. the table is updated bi-monthly with information from the Federal Register and other sources, including direct contact with regulatory agencies. Each table entry provides a chronological record of the rulemaking process for that initiative with an abstract and a projection of further action.

  15. Two-dimensional thermography image retrieval from zig-zag scanned data with TZ-SCAN

    NASA Astrophysics Data System (ADS)

    Okumura, Hiroshi; Yamasaki, Ryohei; Arai, Kohei

    2008-10-01

    TZ-SCAN is a simple and low cost thermal imaging device which consists of a single point radiation thermometer on a tripod with a pan-tilt rotator, a DC motor controller board with a USB interface, and a laptop computer for rotator control, data acquisition, and data processing. TZ-SCAN acquires a series of zig-zag scanned data and stores the data as CSV file. A 2-D thermal distribution image can be retrieved by using the second quefrency peak calculated from TZ-SCAN data. An experiment is conducted to confirm the validity of the thermal retrieval algorithm. The experimental result shows efficient accuracy for 2-D thermal distribution image retrieval.

  16. SU-F-R-18: Updates to the Computational Environment for Radiological Research for Image Analysis

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Apte, Aditya P.; Deasy, Joseph O.

    2016-06-15

    Purpose: To present new tools in CERR for Texture Analysis and Visualization. Method: (1) Quantitative Image Analysis: We added the ability to compute Haralick texture features based on local neighbourhood. The Texture features depend on many parameters used in their derivation. For example: (a) directionality, (b) quantization of image, (c) patch-size for the neighborhood, (d) handling of the edge voxels within the region of interest, (e) Averaging co-occurance matrix vs texture features for different directions etc. A graphical user interface was built to set these parameters and then visualize their impact on the resulting texture maps. The entire functionality wasmore » written in Matlab. Array indexing was used to speed up the texture calculation. The computation speed is very competitive with the ITK library. Moreover, our implementation works with multiple CPUs and the computation time can be further reduced by using multiple processor threads. In order to reduce the Haralick texture maps into scalar features, we propose the use of Texture Volume Histograms. This lets users make use of the entire distribution of texture values within the region of interest rather than using just the mean and the standard deviations. (2) Qualitative/Visualization tools: The derived texture maps are stored as a new scan (derived) within CERR’s planC data structure. A display that compares various scans was built to show the raw image and the derived texture maps side-by-side. These images are positionally linked and can be navigated together. CERR’s graphics handling was updated and sped-up to be compatible with the newer Matlab versions. As a result, the users can use (a) different window levels and colormaps for different viewports, (b) click-and-drag or use mouse scroll-wheel to navigate slices. Results: The new features and updates are available via https://www.github.com/adityaapte/cerr . Conclusion: Features added to CERR increase its utility in Radiomics and

  17. NASA Update

    NASA Image and Video Library

    2009-07-20

    Alan Ladwig, senior advisor to the NASA Administator, far left, makes a point as he introduces NASA Administrator Charles F. Bolden Jr. and Deputy Administrator Lori Garver at a NASA Update,Tuesday, July 21, 2009, at NASA Headquarters in Washington. Bolden, NASA's 12th Administrator and Garver took the time to introduce themselves and outline their vision for the agency going forward. No questions were taken during the session. Photo Credit: (NASA/Bill Ingalls)

  18. Constellation Program Update

    NASA Image and Video Library

    2006-06-04

    Dean Acosta, NASA Deputy Assistant Administrator and Press Secretary, left, moderates a NASA Update with NASA Administrator Michael Griffin, second from left, Scott J. Horowitz, NASA Associate Administrator for Exploration Systems and Jeff Hanley, Constellation Program Manager, right, on Wednesday, June 5, 2006, at NASA Headquarters in Washington. Photo Credit: (NASA/Bill Ingalls)

  19. Single-Trial Event-Related Potential Correlates of Belief Updating

    PubMed Central

    Murawski, Carsten; Bode, Stefan

    2015-01-01

    Abstract Belief updating—the process by which an agent alters an internal model of its environment—is a core function of the CNS. Recent theory has proposed broad principles by which belief updating might operate, but more precise details of its implementation in the human brain remain unclear. In order to address this question, we studied how two components of the human event-related potential encoded different aspects of belief updating. Participants completed a novel perceptual learning task while electroencephalography was recorded. Participants learned the mapping between the contrast of a dynamic visual stimulus and a monetary reward and updated their beliefs about a target contrast on each trial. A Bayesian computational model was formulated to estimate belief states at each trial and was used to quantify the following two variables: belief update size and belief uncertainty. Robust single-trial regression was used to assess how these model-derived variables were related to the amplitudes of the P3 and the stimulus-preceding negativity (SPN), respectively. Results showed a positive relationship between belief update size and P3 amplitude at one fronto-central electrode, and a negative relationship between SPN amplitude and belief uncertainty at a left central and a right parietal electrode. These results provide evidence that belief update size and belief uncertainty have distinct neural signatures that can be tracked in single trials in specific ERP components. This, in turn, provides evidence that the cognitive mechanisms underlying belief updating in humans can be described well within a Bayesian framework. PMID:26473170

  20. 24 CFR 50.36 - Updating of environmental reviews.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 24 Housing and Urban Development 1 2011-04-01 2011-04-01 false Updating of environmental reviews... Urban Development PROTECTION AND ENHANCEMENT OF ENVIRONMENTAL QUALITY Environmental Assessments and Related Reviews § 50.36 Updating of environmental reviews. The environmental review must be re-evaluated...

  1. 24 CFR 50.36 - Updating of environmental reviews.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 24 Housing and Urban Development 1 2010-04-01 2010-04-01 false Updating of environmental reviews... Urban Development PROTECTION AND ENHANCEMENT OF ENVIRONMENTAL QUALITY Environmental Assessments and Related Reviews § 50.36 Updating of environmental reviews. The environmental review must be re-evaluated...

  2. Updated polychlorinated biphenyl mass budget for Lake Michigan

    EPA Science Inventory

    This study revisits and updates the Lake Michigan Mass Balance Project (LMMBP) for polychlorinated biphenyls (PCBs) that was conducted in 1994-1995. This work uses recent concentrations of PCBs in tributary and open lake water, air, and sediment to calculate an updated mass budg...

  3. Guidance for updating clinical practice guidelines: a systematic review of methodological handbooks.

    PubMed

    Vernooij, Robin W M; Sanabria, Andrea Juliana; Solà, Ivan; Alonso-Coello, Pablo; Martínez García, Laura

    2014-01-02

    Updating clinical practice guidelines (CPGs) is a crucial process for maintaining the validity of recommendations. Methodological handbooks should provide guidance on both developing and updating CPGs. However, little is known about the updating guidance provided by these handbooks. We conducted a systematic review to identify and describe the updating guidance provided by CPG methodological handbooks and included handbooks that provide updating guidance for CPGs. We searched in the Guidelines International Network library, US National Guidelines Clearinghouse and MEDLINE (PubMed) from 1966 to September 2013. Two authors independently selected the handbooks and extracted the data. We used descriptive statistics to analyze the extracted data and conducted a narrative synthesis. We included 35 handbooks. Most handbooks (97.1%) focus mainly on developing CPGs, including variable degrees of information about updating. Guidance on identifying new evidence and the methodology of assessing the need for an update is described in 11 (31.4%) and eight handbooks (22.8%), respectively. The period of time between two updates is described in 25 handbooks (71.4%), two to three years being the most frequent (40.0%). The majority of handbooks do not provide guidance for the literature search, evidence selection, assessment, synthesis, and external review of the updating process. Guidance for updating CPGs is poorly described in methodological handbooks. This guidance should be more rigorous and explicit. This could lead to a more optimal updating process, and, ultimately to valid trustworthy guidelines.

  4. Three-dimensional scanning confocal laser microscope

    DOEpatents

    Anderson, R. Rox; Webb, Robert H.; Rajadhyaksha, Milind

    1999-01-01

    A confocal microscope for generating an image of a sample includes a first scanning element for scanning a light beam along a first axis, and a second scanning element for scanning the light beam at a predetermined amplitude along a second axis perpendicular to the first axis. A third scanning element scans the light beam at a predetermined amplitude along a third axis perpendicular to an imaging plane defined by the first and second axes. The second and third scanning element are synchronized to scan at the same frequency. The second and third predetermined amplitudes are percentages of their maximum amplitudes. A selector determines the second and third predetermined amplitudes such that the sum of the percentages is equal to one-hundred percent.

  5. Eye movement sequence generation in humans: Motor or goal updating?

    PubMed Central

    Quaia, Christian; Joiner, Wilsaan M.; FitzGibbon, Edmond J.; Optican, Lance M.; Smith, Maurice A.

    2011-01-01

    Saccadic eye movements are often grouped in pre-programmed sequences. The mechanism underlying the generation of each saccade in a sequence is currently poorly understood. Broadly speaking, two alternative schemes are possible: first, after each saccade the retinotopic location of the next target could be estimated, and an appropriate saccade could be generated. We call this the goal updating hypothesis. Alternatively, multiple motor plans could be pre-computed, and they could then be updated after each movement. We call this the motor updating hypothesis. We used McLaughlin’s intra-saccadic step paradigm to artificially create a condition under which these two hypotheses make discriminable predictions. We found that in human subjects, when sequences of two saccades are planned, the motor updating hypothesis predicts the landing position of the second saccade in two-saccade sequences much better than the goal updating hypothesis. This finding suggests that the human saccadic system is capable of executing sequences of saccades to multiple targets by planning multiple motor commands, which are then updated by serial subtraction of ongoing motor output. PMID:21191134

  6. Correcting scan-to-scan response variability for a radiochromic film-based reference dosimetry system

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Lewis, David, E-mail: rcfilmconsulting@gmail.com; Devic, Slobodan

    Purpose: In radiochromic film dosimetry systems, measurements are usually obtained from film images acquired on a CCD-based flatbed scanner. The authors investigated factors affecting scan-to-scan response variability leading to increased dose measurement uncertainty. Methods: The authors used flatbed document scanners to repetitively scan EBT3 radiochromic films exposed to doses 0–1000 cGy, together with three neutral density filters and three blue optical filters. Scanning was performed under two conditions: scanner lid closed and scanner lid opened/closed between scans. The authors also placed a scanner in a cold room at 9 °C and later in a room at 22 °C and scanned EBT3 filmsmore » to explore temperature effects. Finally, the authors investigated the effect of altering the distance between the film and the scanner’s light source. Results: Using a measurement protocol to isolate the contribution of the CCD and electronic circuitry of the scanners, the authors found that the standard deviation of response measurements for the EBT3 film model was about 0.17% for one scanner and 0.09% for the second. When the lid of the first scanner was opened and closed between scans, the average scan-to-scan difference of responses increased from 0.12% to 0.27%. Increasing the sample temperature during scanning changed the RGB response values by about −0.17, −0.14, and −0.05%/°C, respectively. Reducing the film-to-light source distance increased the RBG response values about 1.1, 1.3, and 1.4%/mm, respectively. The authors observed that films and film samples were often not flat with some areas up to 8 mm away from the scanner’s glass window. Conclusions: In the absence of measures to deal with the response irregularities, each factor the authors investigated could lead to dose uncertainty >2%. Those factors related to the film-to-light source distance could be particularly impactful since the authors observed many instances where the curl of film samples

  7. Using secure messaging to update medications list in ambulatory care setting.

    PubMed

    Raghu, T S; Frey, Keith; Chang, Yu-Hui; Cheng, Meng-Ru; Freimund, Sharon; Patel, Asha

    2015-10-01

    This study analyzed patient adoption of secure messaging to update medication list in an ambulatory care setting. The objective was to establish demographic differences between users and non-users of secure messaging for medications list update. Efficiency of secure messaging for the updates was compared to fax and telephone based updates. The study used a retrospective, cross-sectional study of patient medical records and pharmacy call logs at Mayo Clinic, Arizona from December 2012 to May 2013, approximately one year after organizing a pharmacy call center for medication updates. A subgroup analysis during a 2-week period was used to measure time to complete update. Main dependent variable is the frequency of medication list updates over the study duration. Technician time required for the update was also utilized. A total of 22,495 outpatient visits were drawn and 18,702 unique patients were included in the primary analysis. A total of 402 unique patients were included in sub-group analysis. Secure message response rate (49.5%) was statistically significantly lower than that for phone calls (54.8%, p<0.001). Time to complete the update was significantly higher for faxed medication lists (Wilcoxon rank-sum tests, p<0.001) when compared to those for secure message or phone. Around 50% of the patients respond to medication update requests before office visit when contacted using phone calls and secure messages. Given the demographic differences between users and non-users of patient portal, mixed mode communication with patients is likely to be the norm for the foreseeable future in outpatient settings. Copyright © 2015. Published by Elsevier Ireland Ltd.

  8. Space Communications and Navigation (SCaN) Integrated Network Architecture Definition Document (ADD). Volume 1; Executive Summary; Revision 1

    NASA Technical Reports Server (NTRS)

    Younes, Badri A.; Schier, James S.

    2010-01-01

    The SCaN Program has defined an integrated network architecture that fully meets the Administrator s mandate to the Program, and will result in a NASA infrastructure capable of providing the needed and enabling communications services to future space missions. The integrated network architecture will increase SCaN operational efficiency and interoperability through standardization, commonality and technology infusion. It will enable NASA missions requiring advanced communication and tracking capabilities such as: a. Optical communication b. Antenna arraying c. Lunar and Mars Relays d. Integrated network management (service management and network control) and integrated service execution e. Enhanced tracking for navigation f. Space internetworking with DTN and IP g. End-to-end security h. Enhanced security services Moreover, the SCaN Program has created an Integrated Network Roadmap that depicts an orchestrated and coherent evolution path toward the target architecture, encompassing all aspects that concern network assets (i.e., operations and maintenance, sustaining engineering, upgrade efforts, and major development). This roadmap identifies major NASA ADPs, and shows dependencies and drivers among the various planned undertakings and timelines. The roadmap is scalable to accommodate timely adjustments in response to Agency needs, goals, objectives and funding. Future challenges to implementing this architecture include balancing user mission needs, technology development, and the availability of funding within NASA s priorities. Strategies for addressing these challenges are to: define a flexible architecture, update the architecture periodically, use ADPs to evaluate options and determine when to make decisions, and to engage the stakeholders in these evaluations. In addition, the SCaN Program will evaluate and respond to mission need dates for technical and operational capabilities to be provided by the SCaN integrated network. In that regard, the architecture

  9. Cosmic Origins Spectrograph : Target Acquisition Performance and Updated Guidelines

    NASA Astrophysics Data System (ADS)

    Penton, Steven V.; Keyes, C.; Osterman, S.; Sahnow, D.; Soderblom, D.; COS IDT Team; STScI COS Team

    2010-01-01

    The Cosmic Origins Spectrograph (COS) is a slit-less spectrograph with a very small aperture (radius = 1.25"). To achieve the desired wavelength accuracy of <15 km/s, HST+COS must center the target to within 0.1” of the center of the aperture. This is the angle subtended by a typical AAS poster when viewed from over 1400 miles away. During SMOV we have fine-tuned the COS target acquisition (TA) procedures to exceed this accuracy for all three COS TA modes; NUV imaging, NUV spectroscopic, and FUV spectroscopic. We will compare all COS TA modes in terms of centering accuracy, efficiency (elapsed time), and required signal-to-noise for all targets suitable for use with COS. We will also provide updated recommendations for the options of all TA modes (e.g., SCAN-SIZE and NUM-POS of ACQ/PEAKD). We have observed in SMOV that HST is providing an excellent initial 1-σ blind pointing accuracy of ±0.4” in both the along-dispersion and cross-dispersion directions. We will discuss the implications of this, and other lessons learned in SMOV, on Cycle 17 and 18 HST+COS TAs.

  10. Center Director's Update

    NASA Image and Video Library

    2016-03-01

    In the Space Shuttle Atlantis exhibit facility at the Kennedy Space Center's Visitor Complex, guests get a close-up look at a plant growth experiment similar to one aboard the International Space Station. This followed a presentation by center director Bob Cabana who updated community leaders on current and future activities at the space center.

  11. The utility of repeat sestamibi scans in patients with primary hyperparathyroidism after an initial negative scan.

    PubMed

    Krishnamurthy, Vikram D; Sound, Sara; Okoh, Alexis K; Yazici, Pinar; Yigitbas, Hakan; Neumann, Donald; Doshi, Krupa; Berber, Eren

    2017-06-01

    We analyzed the utility of repeated sestambi scans in patients with primary hyperparathyroidism and its effects on operative referral. We carried out a retrospective review of patients with primary hyperparathyroidism who underwent repeated sestambi scans exclusively within our health system between 1996-2015. Patient demographic, presentation, laboratory, imaging, operative, and pathologic data were reviewed. Univariate analysis with JMP Pro v12 was used to identify factors associated with conversion from an initial negative to a subsequent positive scan. After exclusion criteria (including reoperations), we identified 49 patients in whom 59% (n = 29) of subsequent scans remained negative and 41% (n = 20) converted to positive. Factors associated with an initial negative to a subsequent positive scan included classic presentation and second scans with iodine subtraction (P = .04). Nonsurgeons were less likely to order an iodine-subtraction scan (P < .05). Fewer patients with negative imaging were referred to surgery (33% vs 100%, P = .005), and median time to operation after the first negative scan was 25 months (range 1.4-119). Surgeon-performed ultrasonography had greater sensitivity and positive predictive value than repeated sestamibi scans. Negative sestambi scans decreased and delayed operative referral. Consequently, we identified several process improvement initiatives, including education regarding superior institutional imaging. Combining all findings, we created an algorithm for evaluating patients with primary hyperparathyroidism after initially negative sestamibi scans, which incorporates surgeon-performed ultrasonography. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Internal scanning method as unique imaging method of optical vortex scanning microscope

    NASA Astrophysics Data System (ADS)

    Popiołek-Masajada, Agnieszka; Masajada, Jan; Szatkowski, Mateusz

    2018-06-01

    The internal scanning method is specific for the optical vortex microscope. It allows to move the vortex point inside the focused vortex beam with nanometer resolution while the whole beam stays in place. Thus the sample illuminated by the focused vortex beam can be scanned just by the vortex point. We show that this method enables high resolution imaging. The paper presents the preliminary experimental results obtained with the first basic image recovery procedure. A prospect of developing more powerful tools for topography recovery with the optical vortex scanning microscope is discussed shortly.

  13. Asteroid Redirect Mission Update

    NASA Image and Video Library

    2017-12-08

    Benjamin Reed, deputy program manager of NASA’s Satellite Servicing Capabilities Office, shows Dr. Holdren the technologies that NASA is developing for the Restore-L satellite servicing mission. NASA will launch the Restore-L servicer in 2020 to refuel a live satellite and demonstrate that a suite of satellite-servicing technologies are operational. More info: Asteroid Redirect Mission Update – On Sept. 14, 2016, NASA provided an update on the Asteroid Redirect Mission (ARM) and how it contributes to the agency’s journey to Mars and protection of Earth. The presentation took place in the Robotic Operations Center at NASA’s Goddard Space Flight Center in Greenbelt, Maryland. Assistant to the President for Science and Technology Dr. John P. Holdren, NASA Administrator Charles Bolden and NASA’s ARM Program Director, Dr. Michele Gates discussed the latest update regarding the mission. They explained the mission’s scientific and technological benefits and how ARM will demonstrate technology for defending Earth from potentially hazardous asteroids. The briefing aired live on NASA TV and the agency’s website. For more information about ARM go to www.nasa.gov/arm. Credit: NASA/Goddard/Debbie Mccallum NASA image use policy. NASA Goddard Space Flight Center enables NASA’s mission through four scientific endeavors: Earth Science, Heliophysics, Solar System Exploration, and Astrophysics. Goddard plays a leading role in NASA’s accomplishments by contributing compelling scientific knowledge to advance the Agency’s mission. Follow us on Twitter Like us on Facebook Find us on Instagram

  14. Environmental Regulatory Update Table, May--June 1994

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Houlberg, L.M.; Hawkins, G.T.; Bock, R.E.

    1994-07-01

    The Environmental Regulatory Update Table provides information on regulatory initiatives of interest to DOE operations and contractor staff with environmental management responsibilities. The table is updated bimonthly with information from the Federal Register and other sources, including direct contact with regulatory agencies. Each table entry provides a chronological record of the rulemaking process for that initiative with an abstract and a projection of further action.

  15. Environmental Regulatory Update Table, January--February 1993

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Houlberg, L.M.; Hawkins, G.T.; Salk, M.S.

    1993-03-01

    The Environmental Regulatory Update Table provides information on regulatory initiatives of interest to DOE operations and contractor staff with environmental management responsibilities. The table is updated bi-monthly with information from the Federal Register and other sources, including direct contact with regulatory agencies. Each table entry provides a chronological record of the rulemaking process for that initiative with an abstract and a projection of further action.

  16. Environmental regulatory update table, March--April 1994

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Houlberg, L.M.; Hawkins, G.T.; Bock, R.E.

    1994-03-01

    The Environmental Regulatory Update Table provides information on regulatory initiatives of interest to DOE operations and contractor staff with environmental management responsibilities. The table is updated bi-monthly with information from the Federal Register and other sources, including direct contact with regulatory agencies. Each table entry provides a chronological record of the rulemaking process for that initiative with an abstract and a projection of further action.

  17. Environmental regulatory update table, September--October 1992

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Houlberg, L.M.; Hawkins, G.T.; Lewis, E.B.

    1992-11-01

    The Environmental Regulatory Update Table provides information on regulatory initiatives of interest to DOE operations and contractor staff with environmental management responsibilities. The table is updated bi-monthly with information from the Federal Register and other sources, including direct contact with regulatory agencies. Each table entry provides a chronological record of the rulemaking process for that initiative with an abstract and a projection of further action.

  18. Environmental Regulatory Update Table, September/October 1993

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Houlberg, L.M.; Hawkins, G.T.; Salk, M.S.

    1993-11-01

    The Environmental Regulatory Update Table provides information on regulatory initiatives of interest to DOE operation and contractor staff with environmental management responsibilities. The table is updated bi-monthly with information from the Federal Register and other sources, including direct contact with regulatory agencies. Each table entry provides a chronological record of the rulemaking process for that initiative with an abstract and a projection of further action.

  19. Environmental Regulatory Update Table, January--February 1994

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Houlberg, L.M.; Hawkins, G.T.; Salk, M.S.

    1994-03-01

    The Environmental Regulatory Update Table provides information on regulatory initiatives of interest to DOE operations ad contractor staff with environmental management responsibilities. The table is updated bi-monthly with information from the Federal Register and other sources, including direct contact with regulatory agencies. Each table entry provides a chronological record of the rulemaking process for that initiative with an abstract and a projection of further action.

  20. Environmental regulatory update table November--December 1994

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Houlberg, L.M.; Hawkins, G.T.; Bock, R.E.

    1995-01-01

    The Environmental Regulatory Update Table provides information on regulatory initiatives of interest to DOE operations and contractor staff with environmental management responsibilities. The table is updated bi-monthly with information from the Federal Register and other sources, including direct contact with regulatory agencies. Each table entry provides a chronological record of the rulemaking process for that initiative with an abstract and a projection of further action.

  1. Environmental Regulatory Update Table, November--December 1992

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Houlberg, L.M.; Hawkins, G.T.; Lewis, E.B.

    1993-01-01

    The Environmental Regulatory Update Table provides information on regulatory initiatives of interest to DOE operations and contractor staff with environmental management responsibilities. The table is updated bi-monthly wit information from the Federal Register and other sources, including direct contact with regulatory agencies. Each table entry provides a chronological record of the rulemaking process for that initiative with an abstract and a projection of further action.

  2. Environmental Regulatory Update Table, July--August 1992

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Houlberg, L.M.; Hawkins, G.T.; Lewis, E.B.

    1992-09-01

    The Environmental Regulatory Update Table provides information on regulatory initiatives of interest to DOE operations and contractor staff with environmental management responsibilities. The table is updated bi-monthly with information from the Federal Register and other sources, including direct contact with regulatory agencies. Each table entry provides a chronological record of the rulemaking process for that initiative with an abstract and a projection of further action.

  3. Environmental Regulatory Update Table July/August 1993

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Houlberg, L.M.; Hawkins, G.T.; Salk, M.S.

    1993-09-01

    The Environmental Regulatory Update Table provides information on regulatory initiatives of interest to DOE operations and contractor staff with environmental management responsibilities. The table is updated bi-monthly with information from the Federal Register and other sources, including direct contact with regulatory agencies. Each table entry provides a chronological record of the rulemaking process for that initiative with an abstract and a projection of further action.

  4. Environmental Regulatory Update Table, March/April 1993

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Houlberg, L.M.; Hawkins, G.T.; Salk, M.S.

    1993-05-01

    The Environmental Regulatory Update Table provides information on regulatory initiatives of interest to DOE operations and contractor staff with environmental management responsibilities. The table is updated bimonthly with information from the Federal Register and other sources, including direct contact with regulatory agencies. Each table entry provides a chronological record of the rulemaking process for that initiative with an abstract and a projection of further action.

  5. Environmental regulatory update table, July/August 1994

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Houlberg, L.M.; Hawkins, G.T.; Bock, R.E.

    1994-09-01

    The Environmental Regulatory Update Table provides information on regulatory initiatives of interest to DOE operations and contractor staff with environmental management responsibilities. The table is updated bi-monthly with information from the Federal Register and other sources, including direct contact with regulatory agencies. Each table entry provides a chronological record of the rulemaking process for that initiative with an abstract and a projection of further action.

  6. Environmental Regulatory Update Table, November--December 1993

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Houlberg, L.M.; Hawkins, G.T.; Salk, M.S.

    1994-01-01

    The Environmental Regulatory Update Table provides information on regulatory of interest to DOE operations and contractor staff with environmental management responsibilities. The table is updated bi-monthly with information from the Federal Register and other sources, including direct contact with regulatory agencies. Each table entry provides a chronological record of the rulemaking process for that initiative with an abstract and a projection of further action.

  7. Environmental Regulatory Update Table, May/June 1993

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Houlberg, L.M.; Hawkins, G.T.; Salk, M.S.

    1993-07-01

    The Environmental Regulatory Update Table provides information on regulatory initiatives of interest to DOE operations and contractor staff with environmental management responsibilities. The table is updated bimonthly with information from the Federal Register and other sources, including direct contact with regulatory agencies. Each table entry provides a chronological record of the rulemaking process for that initiative with an abstract and a projection of further action.

  8. 75 FR 3987 - Annual Update of Filing Fees

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-01-26

    ... updating is to adjust the fees on the basis of the Commission's costs for Fiscal Year 2009. DATES... fees on the basis of the Commission's Fiscal Year 2009 costs. The adjusted fees announced in this...] Annual Update of Filing Fees January 20, 2010. AGENCY: Federal Energy Regulatory Commission. ACTION...

  9. 76 FR 9641 - Annual Update of Filing Fees

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-02-22

    ... purpose of updating is to adjust the fees on the basis of the Commission's costs for Fiscal Year 2010... basis of the Commission's Fiscal Year 2010 costs. The adjusted fees announced in this notice are...] Annual Update of Filing Fees February 14, 2011. AGENCY: Federal Energy Regulatory Commission, Energy...

  10. 10 CFR 72.248 - Safety analysis report updating.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 10 Energy 2 2010-01-01 2010-01-01 false Safety analysis report updating. 72.248 Section 72.248 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) LICENSING REQUIREMENTS FOR THE INDEPENDENT STORAGE OF... Approval of Spent Fuel Storage Casks § 72.248 Safety analysis report updating. (a) Each certificate holder...

  11. Revised Kuppuswamy's Socioeconomic Status Scale: Explained and Updated.

    PubMed

    Sharma, Rahul

    2017-10-15

    Some of the facets of the Kuppuswamy's socioeconomic status scale sometimes create confusion and require explanation on how to classify, and need some minor updates to bring the scale up-to-date. This article provides a revised scale that allows for the real-time update of the scale.

  12. Revised Kuppuswamy's Socioeconomic Status Scale: Explained and Updated.

    PubMed

    Sharma, Rahul

    2017-08-26

    Some of the facets of the Kuppuswamy's socioeconomic status scale sometimes create confusion and require explanation on how to classify, and need some minor updates to bring the scale up-to-date. This article provides a revised scale that allows for the real-time update of the scale.

  13. The Scanning Process: Getting Started.

    ERIC Educational Resources Information Center

    Renfro, William L.; Morrison, James L.

    1983-01-01

    Scanning the external environment will become more essential to colleges in the coming decade. Developing an environmental scanning system can identify important emerging issues that may constitute either threats or opportunities. The organizational features of a mature scanning process are described. (MLW)

  14. Correlative fluorescence and scanning transmission electron microscopy of quantum dot-labeled proteins on whole cells in liquid.

    PubMed

    Peckys, Diana B; Bandmann, Vera; de Jonge, Niels

    2014-01-01

    Correlative fluorescence microscopy combined with scanning transmission electron microscopy (STEM) of cells fully immersed in liquid is a new methodology with many application areas. Proteins, in live cells immobilized on microchips, are labeled with fluorescent quantum dot nanoparticles. In this protocol, the epidermal growth factor receptor (EGFR) is labeled. The cells are fixed after a selected labeling time, for example, 5 min as needed to form EGFR dimers. The microchip with cells is then imaged with fluorescence microscopy. Thereafter, STEM can be accomplished in two ways. The microchip with the labeled cells and one microchip with a spacer are assembled into a special microfluidic device and imaged with dedicated high-voltage STEM. Alternatively, thin edges of cells can be studied with environmental scanning electron microscopy with a STEM detector, by placing a microchip with cells in a cooled wet environment. © 2014 Elsevier Inc. All rights reserved.

  15. Radioisotope scanning in osseous sarcoidosis

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Rohatgi, P.K.

    1980-01-01

    Technetium-99m (/sup 99m/Tc)-labeled pyrophosphate or diphosphonate compounds and gallium-67 citrate (/sup 67/Ga) are two radionuclide scanning agents that are in widespread use in clinical practice. Technetium-99m pyrophosphate is used extensively for bone scanning to detect metastatic bone disease, benign bone tumors, osteomyelitis, benign hypertrophic osteoarthropathy, and Paget's disease. Only two reports describe abnormal /sup 99m/Tc/ pyrophosphate bone scans in four patients with osseous sarcoidosis. Gallium-67 scans are used primarily to localize neoplastic or inflammatory lesions anywhere in the body. In recent years /sup 67/Ga scans have also been used to detect the presence of both pulmonary and extrapulmonary sarcoidosis, butmore » there are no reports describing abnormal uptake of gallium in patients with osseous sarcoidosis. This report describes experience with radioisotope scanning in two patients with osseous sarcoidosis.« less

  16. Mouse manipulation through single-switch scanning.

    PubMed

    Blackstien-Adler, Susie; Shein, Fraser; Quintal, Janet; Birch, Shae; Weiss, Patrice L Tamar

    2004-01-01

    Given the current extensive reliance on the graphical user interface, independent access to computer software requires that users be able to manipulate a pointing device of some type (e.g., mouse, trackball) or be able to emulate a mouse by some other means (e.g., scanning). The purpose of the present study was to identify one or more optimal single-switch scanning mouse emulation strategies. Four alternative scanning strategies (continuous Cartesian, discrete Cartesian, rotational, and hybrid quadrant/continuous Cartesian) were selected for testing based on current market availability as well as on theoretical considerations of their potential speed and accuracy. Each strategy was evaluated using a repeated measures study design by means of a test program that permitted mouse emulation via any one of four scanning strategies in a motivating environment; response speed and accuracy could be automatically recorded and considered in view of the motor, cognitive, and perceptual demands of each scanning strategy. Ten individuals whose disabilities required them to operate a computer via single-switch scanning participated in the study. Results indicated that Cartesian scanning was the preferred and most effective scanning strategy. There were no significant differences between results from the Continuous Cartesian and Discrete Cartesian scanning strategies. Rotational scanning was quite slow with respect to the other strategies, although it was equally accurate. Hybrid Quadrant scanning improved access time but at the cost of fewer correct selections. These results demonstrated the importance of testing and comparing alternate single-switch scanning strategies.

  17. Small molecule inhibition of fibroblast growth factor receptors in cancer.

    PubMed

    Liang, Guang; Chen, Gaozhi; Wei, Xiaoyan; Zhao, Yunjie; Li, Xiaokun

    2013-10-01

    Fibroblast growth factors (FGFs) signal through FGF receptors (FGFRs), which are a sub-family of the superfamily of receptor tyrosine kinases, to regulate human development and metabolism. Uncontrolled FGF signaling is responsible for diverse array of developmental disorders, most notably skeletal syndromes due to FGFR gain-of-function mutations. Studies in the last few years have provided significant evidence for the importance of FGF signaling in the pathogenesis of diverse cancers, including endometrial and bladder cancers. FGFs are both potent mitogenic and angiogenic factors and can contribute to carcinogenesis by stimulating cell proliferation and tumor angiogenesis. Gene knockout and pharmacological inhibition of FGFRs in in vivo and in vitro models validate FGFRs as a target for cancer treatment. Considerable efforts are being expended to develop specific, small-molecule inhibitors for treating FGFR-driven cancers. Recent reviews on the FGF/FGFR system have focused primarily on signaling, pathophysiology, and functions in cancer. In this article, we review the key roles of FGFR in cancer, provide an update on the status of clinical trials with small-molecule FGFR inhibitors, and discuss how the current structural data on FGFR kinases guide the design and characterization of new FGFR inhibitors. Copyright © 2013 Elsevier Ltd. All rights reserved.

  18. Anatomical relationships between serotonin 5-HT2A and dopamine D2 receptors in living human brain.

    PubMed

    Ishii, Tatsuya; Kimura, Yasuyuki; Ichise, Masanori; Takahata, Keisuke; Kitamura, Soichiro; Moriguchi, Sho; Kubota, Manabu; Zhang, Ming-Rong; Yamada, Makiko; Higuchi, Makoto; Okubo, Yoshinori; Suhara, Tetsuya

    2017-01-01

    Seven healthy volunteers underwent PET scans with [18F]altanserin and [11C]FLB 457 for 5-HT2A and D2 receptors, respectively. As a measure of receptor density, a binding potential (BP) was calculated from PET data for 76 cerebral cortical regions. A correlation matrix was calculated between the binding potentials of [18F]altanserin and [11C]FLB 457 for those regions. The regional relationships were investigated using a bicluster analysis of the correlation matrix with an iterative signature algorithm. We identified two clusters of regions. The first cluster identified a distinct profile of correlation coefficients between 5-HT2A and D2 receptors, with the former in regions related to sensorimotor integration (supplementary motor area, superior parietal gyrus, and paracentral lobule) and the latter in most cortical regions. The second cluster identified another distinct profile of correlation coefficients between 5-HT2A receptors in the bilateral hippocampi and D2 receptors in most cortical regions. The observation of two distinct clusters in the correlation matrix suggests regional interactions between 5-HT2A and D2 receptors in sensorimotor integration and hippocampal function. A bicluster analysis of the correlation matrix of these neuroreceptors may be beneficial in understanding molecular networks in the human brain.

  19. Device localization and dynamic scan plane selection using a wireless magnetic resonance imaging detector array.

    PubMed

    Riffe, Matthew J; Yutzy, Stephen R; Jiang, Yun; Twieg, Michael D; Blumenthal, Colin J; Hsu, Daniel P; Pan, Li; Gilson, Wesley D; Sunshine, Jeffrey L; Flask, Christopher A; Duerk, Jeffrey L; Nakamoto, Dean; Gulani, Vikas; Griswold, Mark A

    2014-06-01

    A prototype wireless guidance device using single sideband amplitude modulation (SSB) is presented for a 1.5T magnetic resonance imaging system. The device contained three fiducial markers each mounted to an independent receiver coil equipped with wireless SSB technology. Acquiring orthogonal projections of these markers determined the position and orientation of the device, which was used to define the scan plane for a subsequent image acquisition. Device localization and scan plane update required approximately 30 ms, so it could be interleaved with high temporal resolution imaging. Since the wireless device is used for localization and does not require full imaging capability, the design of the SSB wireless system was simplified by allowing an asynchronous clock between the transmitter and receiver. When coupled to a high readout bandwidth, the error caused by the lack of a shared frequency reference was quantified to be less than one pixel (0.78 mm) in the projection acquisitions. Image guidance with the prototype was demonstrated with a phantom where a needle was successfully guided to a target and contrast was delivered. The feasibility of active tracking with a wireless detector array is demonstrated. Wireless arrays could be incorporated into devices to assist in image-guided procedures. Copyright © 2013 Wiley Periodicals, Inc.

  20. NAVIS-An UGV Indoor Positioning System Using Laser Scan Matching for Large-Area Real-Time Applications

    PubMed Central

    Tang, Jian.; Chen, Yuwei.; Jaakkola, Anttoni.; Liu, Jinbing.; Hyyppä, Juha.; Hyyppä, Hannu.

    2014-01-01

    Laser scan matching with grid-based maps is a promising tool for real-time indoor positioning of mobile Unmanned Ground Vehicles (UGVs). While there are critical implementation problems, such as the ability to estimate the position by sensing the unknown indoor environment with sufficient accuracy and low enough latency for stable vehicle control, further development work is necessary. Unfortunately, most of the existing methods employ heuristics for quick positioning in which numerous accumulated errors easily lead to loss of positioning accuracy. This severely restricts its applications in large areas and over lengthy periods of time. This paper introduces an efficient real-time mobile UGV indoor positioning system for large-area applications using laser scan matching with an improved probabilistically-motivated Maximum Likelihood Estimation (IMLE) algorithm, which is based on a multi-resolution patch-divided grid likelihood map. Compared with traditional methods, the improvements embodied in IMLE include: (a) Iterative Closed Point (ICP) preprocessing, which adaptively decreases the search scope; (b) a totally brute search matching method on multi-resolution map layers, based on the likelihood value between current laser scan and the grid map within refined search scope, adopted to obtain the global optimum position at each scan matching; and (c) a patch-divided likelihood map supporting a large indoor area. A UGV platform called NAVIS was designed, manufactured, and tested based on a low-cost robot integrating a LiDAR and an odometer sensor to verify the IMLE algorithm. A series of experiments based on simulated data and field tests with NAVIS proved that the proposed IMEL algorithm is a better way to perform local scan matching that can offer a quick and stable positioning solution with high accuracy so it can be part of a large area localization/mapping, application. The NAVIS platform can reach an updating rate of 12 Hz in a feature-rich environment and 2 Hz

  1. NAVIS-An UGV indoor positioning system using laser scan matching for large-area real-time applications.

    PubMed

    Tang, Jian; Chen, Yuwei; Jaakkola, Anttoni; Liu, Jinbing; Hyyppä, Juha; Hyyppä, Hannu

    2014-07-04

    Laser scan matching with grid-based maps is a promising tool for real-time indoor positioning of mobile Unmanned Ground Vehicles (UGVs). While there are critical implementation problems, such as the ability to estimate the position by sensing the unknown indoor environment with sufficient accuracy and low enough latency for stable vehicle control, further development work is necessary. Unfortunately, most of the existing methods employ heuristics for quick positioning in which numerous accumulated errors easily lead to loss of positioning accuracy. This severely restricts its applications in large areas and over lengthy periods of time. This paper introduces an efficient real-time mobile UGV indoor positioning system for large-area applications using laser scan matching with an improved probabilistically-motivated Maximum Likelihood Estimation (IMLE) algorithm, which is based on a multi-resolution patch-divided grid likelihood map. Compared with traditional methods, the improvements embodied in IMLE include: (a) Iterative Closed Point (ICP) preprocessing, which adaptively decreases the search scope; (b) a totally brute search matching method on multi-resolution map layers, based on the likelihood value between current laser scan and the grid map within refined search scope, adopted to obtain the global optimum position at each scan matching; and (c) a patch-divided likelihood map supporting a large indoor area. A UGV platform called NAVIS was designed, manufactured, and tested based on a low-cost robot integrating a LiDAR and an odometer sensor to verify the IMLE algorithm. A series of experiments based on simulated data and field tests with NAVIS proved that the proposed IMEL algorithm is a better way to perform local scan matching that can offer a quick and stable positioning solution with high accuracy so it can be part of a large area localization/mapping, application. The NAVIS platform can reach an updating rate of 12 Hz in a feature-rich environment and 2 Hz

  2. 5-HT2a receptor in mPFC influences context-guided reconsolidation of object memory in perirhinal cortex.

    PubMed

    Morici, Juan Facundo; Miranda, Magdalena; Gallo, Francisco Tomás; Zanoni, Belén; Bekinschtein, Pedro; Weisstaub, Noelia V

    2018-05-02

    Context-dependent memories may guide adaptive behavior relaying in previous experience while updating stored information through reconsolidation. Retrieval can be triggered by partial and shared cues. When the cue is presented, the most relevant memory should be updated. In a contextual version of the object recognition task, we examined the effect of medial PFC (mPFC) serotonin 2a receptor (5-HT2aR) blockade during retrieval in reconsolidation of competing objects memories. We found that mPFC 5-HT2aR controls retrieval and reconsolidation of object memories in the perirhinal cortex (PRH), but not in the dorsal hippocampus in rats. Also, reconsolidation of objects memories in PRH required a functional interaction between the ventral hippocampus and the mPFC. Our results indicate that in the presence of conflicting information at retrieval, mPFC 5-HT2aR may facilitate top-down context-guided control over PRH to control the behavioral response and object memory reconsolidation. © 2018, Morici et al.

  3. 5-HT2a receptor in mPFC influences context-guided reconsolidation of object memory in perirhinal cortex

    PubMed Central

    Morici, Juan Facundo; Miranda, Magdalena; Gallo, Francisco Tomás; Zanoni, Belén; Bekinschtein, Pedro

    2018-01-01

    Context-dependent memories may guide adaptive behavior relaying in previous experience while updating stored information through reconsolidation. Retrieval can be triggered by partial and shared cues. When the cue is presented, the most relevant memory should be updated. In a contextual version of the object recognition task, we examined the effect of medial PFC (mPFC) serotonin 2a receptor (5-HT2aR) blockade during retrieval in reconsolidation of competing objects memories. We found that mPFC 5-HT2aR controls retrieval and reconsolidation of object memories in the perirhinal cortex (PRH), but not in the dorsal hippocampus in rats. Also, reconsolidation of objects memories in PRH required a functional interaction between the ventral hippocampus and the mPFC. Our results indicate that in the presence of conflicting information at retrieval, mPFC 5-HT2aR may facilitate top-down context-guided control over PRH to control the behavioral response and object memory reconsolidation. PMID:29717980

  4. National Solar Radiation Database 1991-2005 Update: User's Manual

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Wilcox, S.

    2007-04-01

    This manual describes how to obtain and interpret the data products from the updated 1991-2005 National Solar Radiation Database (NSRDB). This is an update of the original 1961-1990 NSRDB released in 1992.

  5. Comparison of sequential planar 177Lu-DOTA-TATE dosimetry scans with 68Ga-DOTA-TATE PET/CT images in patients with metastasized neuroendocrine tumours undergoing peptide receptor radionuclide therapy.

    PubMed

    Sainz-Esteban, Aurora; Prasad, Vikas; Schuchardt, Christiane; Zachert, Carolin; Carril, José Manuel; Baum, Richard P

    2012-03-01

    The aim of the study was to compare sequential (177)Lu-DOTA-TATE planar scans ((177)Lu-DOTA-TATE) in patients with metastasized neuroendocrine tumours (NET) acquired during peptide receptor radionuclide therapy (PRRT) for dosimetry purposes with the pre-therapeutic (68)Ga-DOTA-TATE positron emission tomography (PET)/CT ((68)Ga-DOTA-TATE) maximum intensity projection (MIP) images obtained in the same patients concerning the sensitivity of the different methods. A total of 44 patients (59 ± 11 years old) with biopsy-proven NET underwent (68)Ga-DOTA-TATE and (177)Lu-DOTA-TATE imaging within 7.9 ± 7.5 days between the two examinations. (177)Lu-DOTA-TATE planar images were acquired at 0.5, 2, 24, 48 and 72 h post-injection; lesions were given a score from 0 to 4 depending on the uptake of the radiopharmaceutical (0 being lowest and 4 highest). The number of tumour lesions which were identified on (177)Lu-DOTA-TATE scans (in relation to the acquisition time after injection of the therapeutic dose as well as with regard to the body region) was compared to those detected on (68)Ga-DOTA-TATE studies obtained before PRRT. A total of 318 lesions were detected; 280 (88%) lesions were concordant. Among the discordant lesions, 29 were (68)Ga-DOTA-TATE positive and (177)Lu-DOTA-TATE negative, whereas 9 were (68)Ga-DOTA-TATE negative and (177)Lu-DOTA-TATE positive. The sensitivity, positive predictive value and accuracy for (177)Lu-DOTA-TATE as compared to (68)Ga-DOTA-TATE were 91, 97 and 88%, respectively. Significantly more lesions were seen on the delayed (72 h) (177)Lu-DOTA-TATE images (91%) as compared to the immediate (30 min) images (68%). The highest concordance was observed for bone metastases (97%) and the lowest for head/neck lesions (75%). Concordant lesions (n = 77; mean size 3.8 cm) were significantly larger than discordant lesions (n = 38; mean size 1.6 cm) (p < 0.05). No such significance was found for differences in maximum standardized uptake value (SUV

  6. Noninvasive detection of activating estrogen receptor 1 (ESR1) mutations in estrogen receptor-positive metastatic breast cancer.

    PubMed

    Guttery, David S; Page, Karen; Hills, Allison; Woodley, Laura; Marchese, Stephanie D; Rghebi, Basma; Hastings, Robert K; Luo, Jinli; Pringle, J Howard; Stebbing, Justin; Coombes, R Charles; Ali, Simak; Shaw, Jacqueline A

    2015-07-01

    Activating mutations in the estrogen receptor 1 (ESR1) gene are acquired on treatment and can drive resistance to endocrine therapy. Because of the spatial and temporal limitations of needle core biopsies, our goal was to develop a highly sensitive, less invasive method of detecting activating ESR1 mutations via circulating cell-free DNA (cfDNA) and tumor cells as a "liquid biopsy." We developed a targeted 23-amplicon next-generation sequencing (NGS) panel for detection of hot-spot mutations in ESR1, phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PIK3CA), tumor protein p53 (TP53), fibroblast growth factor receptor 1 (FGFR1), and fibroblast growth factor receptor 2 (FGFR2) in 48 patients with estrogen receptor-α-positive metastatic breast cancer who were receiving systemic therapy. Selected mutations were validated using droplet digital PCR (ddPCR). Nine baseline cfDNA samples had an ESR1 mutation. NGS detected 3 activating mutations in ESR1, and 3 hot-spot mutations in PIK3CA, and 3 in TP53 in baseline cfDNA, and the ESR1 p.D538G mutation in 1 matched circulating tumor cell sample. ddPCR analysis was more sensitive than NGS and identified 6 additional baseline cfDNA samples with the ESR1 p.D538G mutation at a frequency of <1%. In serial blood samples from 11 patients, 4 showed changes in cfDNA, 2 with emergence of a mutation in ESR1. We also detected a low frequency ESR1 mutation (1.3%) in cfDNA of 1 primary patient who was thought to have metastatic disease but was clear by scans. Early identification of ESR1 mutations by liquid biopsy might allow for cessation of ineffective endocrine therapies and switching to other treatments, without the need for tissue biopsy and before the emergence of metastatic disease. © 2015 American Association for Clinical Chemistry.

  7. Updates to the Demographic and Spatial Allocation Models to ...

    EPA Pesticide Factsheets

    EPA's announced the availability of the final report, Updates to the Demographic and Spatial Allocation Models to Produce Integrated Climate and Land Use Scenarios (ICLUS) (Version 2). This update furthered land change modeling by providing nationwide housing development scenarios up to 2100. This newest version includes updated population and land use data sets and addresses limitations identified in ICLUS v1 in both the migration and spatial allocation models. The companion user guide (Final Report) describes the development of ICLUS v2 and the updates that were made to the original data sets and the demographic and spatial allocation models. The GIS tool enables users to run SERGoM with the population projections developed for the ICLUS project and allows users to modify the spatial allocation housing density across the landscape.

  8. Solar System Montage Updated

    NASA Image and Video Library

    1999-05-03

    This is an updated montage of planetary images taken by spacecraft managed by NASA’s Jet Propulsion Laboratory in Pasadena, CA. Included are from top to bottom images of Mercury, Venus, Earth and Moon, Mars, Jupiter, Saturn, Uranus and Neptune.

  9. Update in women's health.

    PubMed

    Ganschow, Pamela S; Jacobs, Elizabeth A; Mackinnon, Jennifer; Charney, Pamela

    2009-06-01

    The aim of this clinical update is to summarize articles and guidelines published in the last year with the potential to change current clinical practice as it relates to women's health. We used two independent search strategies to identify articles relevant to women's health published between March 1, 2007 and February 29, 2008. First, we reviewed the Cochrane Database of Systematic Reviews and journal indices from the ACP Journal Club, Annals of Internal Medicine, Archives of Internal Medicine, British Medical Journal, Circulation, Diabetes, JAMA, JGIM, Journal of Women's Health, Lancet, NEJM, Obstetrics and Gynecology, and Women's Health Journal Watch. Second, we performed a MEDLINE search using the medical subject heading term "sex factors." The authors, who all have clinical and/or research experience in the area of women's health, reviewed all article titles, abstracts, and, when indicated, full publications. We excluded articles related to obstetrical aspects of women's health focusing on those relevant to general internists. We had two acceptance criteria, scientific rigor and potential to impact women's health. We also identified new and/or updated women's health guidelines released during the same time period. We identified over 250 publications with potential relevance to women's health. Forty-six articles were selected for presentation as part of the Clinical Update, and nine were selected for a more detailed discussion in this paper. Evidence-based women's health guidelines are listed in Table 1. Table 1 Important Women's Health Guidelines in 2007-2008: New or Updated Topic Issuing organization Updated recommendations and comments Mammography screening in women 40-4917 ACP Individualized risk assessment and informed decision making should be used to guide decisions about mammography screening in this age group. To aid in the risk assessment, a discussion of the risk factors, which if present in a woman in her 40s increases her risk to above that of an

  10. 32 CFR 635.24 - Updating the COPS MPRS.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 32 National Defense 4 2014-07-01 2013-07-01 true Updating the COPS MPRS. 635.24 Section 635.24... CRIMINAL INVESTIGATIONS LAW ENFORCEMENT REPORTING Offense Reporting § 635.24 Updating the COPS MPRS... ensure that every founded offense is reported into the COPS MPRS. Timely and accurate reporting is...

  11. 32 CFR 635.24 - Updating the COPS MPRS.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 32 National Defense 4 2012-07-01 2011-07-01 true Updating the COPS MPRS. 635.24 Section 635.24... CRIMINAL INVESTIGATIONS LAW ENFORCEMENT REPORTING Offense Reporting § 635.24 Updating the COPS MPRS... ensure that every founded offense is reported into the COPS MPRS. Timely and accurate reporting is...

  12. 32 CFR 635.24 - Updating the COPS MPRS.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 32 National Defense 4 2013-07-01 2013-07-01 false Updating the COPS MPRS. 635.24 Section 635.24... CRIMINAL INVESTIGATIONS LAW ENFORCEMENT REPORTING Offense Reporting § 635.24 Updating the COPS MPRS... ensure that every founded offense is reported into the COPS MPRS. Timely and accurate reporting is...

  13. 76 FR 45482 - Changes to Move Update Standards

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-07-29

    ... POSTAL SERVICE 39 CFR Part 111 Changes to Move Update Standards AGENCY: Postal Service TM . ACTION... of July 12, 2011, a proposed rule pertaining to changes in Move Update standards, which established...: The Postal Service published changes to a proposed rule in the Federal Register on July 12, 2011 (76...

  14. In vitro and in vivo evaluation of 11C-SD5024, a novel PET radioligand for human brain imaging of cannabinoid CB1 receptors

    PubMed Central

    Tsujikawa, Tetsuya; Zoghbi, Sami S.; Hong, Jinsoo; Donohue, Sean R.; Jenko, Kimberly J.; Gladding, Robert L.; Halldin, Christer; Pike, Victor W.; Innis, Robert B.; Fujita, Masahiro

    2013-01-01

    We recently developed a novel cannabinoid subtype-1 (CB1) receptor radioligand 11C-SD5024 for brain imaging. This study aimed to evaluate 11C-SD5024 both in vitro and in vivo and compare it with the other CB1 receptor ligands previously used in humans, i.e., 11C-MePPEP, 11C-OMAR, 18F-MK-9470, and 18F-FMPEP-d2. In vitro experiments were performed to measure dissociation constant (Ki) in human brain and to measure the lipophilicity of five CB1 receptor ligands listed above. In vivo specific binding in monkeys was measured by comparing total distribution volume (VT) at baseline and after full receptor blockade. The kinetics of 11C-SD5024 in humans were evaluated in seven healthy subjects with compartmental modeling. SD5024 showed Ki=0.47 nM, which was at an intermediate level among the five CB1 receptor ligands. Lipophilicity (LogD7.4) was 3.79, which is appropriate for brain imaging. Monkey scans showed high proportion of specific binding: ~80% of VT. In humans, 11C-SD5024 showed peak brain uptake of 1.5–3 standardized uptake value, which was slightly higher than those of 11C-OMAR and 18F-MK-9470. One-compartment model showed good fitting, consistent with the vast majority of brain uptake being specific binding found in the monkey. Regional VT values were consistent with known distribution of CB1 receptors. VT calculated from 80 and 120 min of scan data were strongly correlated (R2=0.97), indicating that 80 min provided adequate information for quantitation and that the influence of radiometabolites was low. Intersubject variability for VT of 11C-SD5024 was 22%, which was low among the five radioligands and indicated precise measurement. In conclusion, 11C-SD5024 has appropriate affinity and lipophilicity, high specific binding, moderate brain uptake, and provides good precision to measure the binding. The results suggest that 11C-SD5024 is slightly better than or equivalent to 11C-OMAR and that both are suitable for clinical studies, especially those that involve

  15. Kennedy Space Center Director Update

    NASA Image and Video Library

    2014-03-06

    CAPE CANAVERAL, Fla. – NASA Kennedy Space Center Director Robert Cabana welcomes community leaders, business executives, educators, community organizers, and state and local government leaders to the Kennedy Space Center Visitor Complex Debus Center for the Kennedy Space Center Director Update. Attendees talked with Cabana and other senior Kennedy managers and visited displays featuring updates on Kennedy programs and projects, including International Space Station, Commercial Crew, Ground System Development and Operations, Launch Services, Center Planning and Development, Technology, KSC Swamp Works and NASA Education. The morning concluded with a tour of the new Space Shuttle Atlantis exhibit at the visitor complex. For more information, visit http://www.nasa.gov/kennedy. Photo credit: NASA/Daniel Casper

  16. 24 CFR 902.51 - Updating of public housing unit address information.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... Service and Satisfaction § 902.51 Updating of public housing unit address information. (a) Electronic updating. The survey process for the Resident Service and Satisfaction Indicator is dependent upon... any points for the PHAS Resident Service and Satisfaction Indicator. (c) Electronic updating of the...

  17. Body CT (CAT Scan)

    MedlinePlus

    ... Resources Professions Site Index A-Z Computed Tomography (CT) - Body Computed tomography (CT) of the body uses ... of CT Scanning of the Body? What is CT Scanning of the Body? Computed tomography, more commonly ...

  18. Who's Who? Memory updating and character reference in children's narratives.

    PubMed

    Whitely, Cristy; Colozzo, Paola

    2013-10-01

    The capacity to update and monitor the contents of working memory is an executive function presumed to play a critical role in language processing. The current study used an individual differences approach to consider the relationship between memory updating and accurate reference to story characters in the narratives of typically developing children. English-speaking children from kindergarten to grade 2 ( N = 63; M age = 7.0 years) completed updating tasks, short-term memory tasks, and narrative productions. The authors used multiple regression to test whether updating accounted for independent variability in referential adequacy. The capacity to update working memory was related to adequate character reference beyond the effects of age and of short-term memory capacity, with the strongest relationship emerging for maintaining reference over multiple utterances. This individual differences study is the first to show a link between updating and performance in a discourse production task for young school-age children. The findings contribute to the growing body of research investigating the role of working memory in shaping language production. This study invites extension to children of different ages and language abilities as well as to other language production tasks.

  19. A review of statistical updating methods for clinical prediction models.

    PubMed

    Su, Ting-Li; Jaki, Thomas; Hickey, Graeme L; Buchan, Iain; Sperrin, Matthew

    2018-01-01

    A clinical prediction model is a tool for predicting healthcare outcomes, usually within a specific population and context. A common approach is to develop a new clinical prediction model for each population and context; however, this wastes potentially useful historical information. A better approach is to update or incorporate the existing clinical prediction models already developed for use in similar contexts or populations. In addition, clinical prediction models commonly become miscalibrated over time, and need replacing or updating. In this article, we review a range of approaches for re-using and updating clinical prediction models; these fall in into three main categories: simple coefficient updating, combining multiple previous clinical prediction models in a meta-model and dynamic updating of models. We evaluated the performance (discrimination and calibration) of the different strategies using data on mortality following cardiac surgery in the United Kingdom: We found that no single strategy performed sufficiently well to be used to the exclusion of the others. In conclusion, useful tools exist for updating existing clinical prediction models to a new population or context, and these should be implemented rather than developing a new clinical prediction model from scratch, using a breadth of complementary statistical methods.

  20. Probing receptor structure/function with chimeric G-protein-coupled receptors.

    PubMed

    Yin, Dezhong; Gavi, Shai; Wang, Hsien-yu; Malbon, Craig C

    2004-06-01

    Owing its name to an image borrowed from Greek mythology, a chimera is seen to represent a new entity created as a composite from existing creatures or, in this case, molecules. Making use of various combinations of three basic domains of the receptors (i.e., exofacial, transmembrane, and cytoplasmic segments) that couple agonist binding into activation of effectors through heterotrimeric G-proteins, molecular pharmacology has probed the basic organization, structure/function relationships of this superfamily of heptahelical receptors. Chimeric G-protein-coupled receptors obviate the need for a particular agonist ligand when the ligand is resistant to purification or, in the case of orphan receptors, is not known. Chimeric receptors created from distant members of the heptahelical receptors enable new strategies in understanding how these receptors transduce agonist binding into receptor activation and may be able to offer insights into the evolution of G-protein-coupled receptors from yeast to humans.