Post-Remediation Radiological Dose Assessment, Linde Site, Tonawanda, New York

Energy Technology Data Exchange (ETDEWEB)

Kamboj, Sunita [Argonne National Lab. (ANL), Argonne, IL (United States); Durham, Lisa A. [Argonne National Lab. (ANL), Argonne, IL (United States)

2014-06-01

A post-remediation radiological dose assessment was conducted for the Formerly Utilized Sites Remedial Action Program (FUSRAP) Linde Site by using the measured residual concentrations of the radionuclides of concern following the completion of the soils remedial action. The site’s FUSRAP-related contaminants of concern (COCs) are radionuclides associated with uranium processing activities conducted by the Manhattan Engineer District (MED) in support of the Nation’s early atomic energy and weapons program and include radium-226 (Ra-226), thorium-230 (Th-230), and total uranium (Utotal). Remedial actions to address Linde Site soils and structures were conducted in accordance with the Record of Decision for the Linde Site, Tonawanda, New York (ROD) (USACE 2000a). In the ROD, the U.S. Army Corps of Engineers (USACE) determined that the cleanup standards found in Title 40, Part 192 of the Code of Federal Regulations (40 CFR Part 192), the standards for cleanup of uranium mill sites designated under the Uranium Mill Tailings Radiation Control Act (UMTRCA), and the Nuclear Regulatory Commission (NRC) standards for decommissioning of licensed uranium and thorium mills, found in 10 CFR Part 40, Appendix A, Criterion 6(6), are Applicable or Relevant and Appropriate Requirements (ARARs) for cleanup of MED-related contamination at the Linde Site. The major elements of this remedy will involve excavation of the soils with COCs above soil cleanup levels and placement of clean materials to meet the other criteria of 40 CFR Part 192.

Analysis list: ERG [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available ERG Blood,Breast,Prostate + hg19 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/ta...rget/ERG.1.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/target/ERG.5.tsv http://dbarchive.bioscienced...bc.jp/kyushu-u/hg19/target/ERG.10.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/colo/ERG.Blood.tsv,http://dbarchive.bioscience...dbc.jp/kyushu-u/hg19/colo/ERG.Breast.tsv,http://dbarchive.bioscience...dbc.jp/kyushu-u/hg19/colo/ERG.Prostate.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/colo/B

Dynamics of hERG closure allow novel insights into hERG blocking by small molecules.

Science.gov (United States)

Schmidtke, Peter; Ciantar, Marine; Theret, Isabelle; Ducrot, Pierre

2014-08-25

Today, drug discovery routinely uses experimental assays to determine very early if a lead compound can yield certain types of off-target activity. Among such off targets is hERG. The ion channel plays a primordial role in membrane repolarization and altering its activity can cause severe heart arrhythmia and sudden death. Despite routine tests for hERG activity, rather little information is available for helping medicinal chemists and molecular modelers to rationally circumvent hERG activity. In this article novel insights into the dynamics of hERG channel closure are described. Notably, helical pairwise closure movements have been observed. Implications and relations to hERG inactivation are presented. Based on these dynamics novel insights on hERG blocker placement are presented, compared to literature, and discussed. Last, new evidence for horizontal ligand positioning is shown in light of former studies on hERG blockers.

Väike pahe või suur kirg? / Katrin Pauts

Index Scriptorium Estoniae

Pauts, Katrin, 1977-

2006-01-01

Veinijoomisest, sigari suitsetamisest ning kaartide tagumisest räägivad sigarisalongi La Casa del Habano perenaine Angela Leima, Tartu Veiniklubi liige Katrin Pärgmäe ja bridzhiklubi president Marion Ründal

Analysis of KATRIN data using Bayesian inference

DEFF Research Database (Denmark)

Riis, Anna Sejersen; Hannestad, Steen; Weinheimer, Christian

2011-01-01

The KATRIN (KArlsruhe TRItium Neutrino) experiment will be analyzing the tritium beta-spectrum to determine the mass of the neutrino with a sensitivity of 0.2 eV (90% C.L.). This approach to a measurement of the absolute value of the neutrino mass relies only on the principle of energy conservation...

Analysis list: Erg [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available Erg Blood,Prostate + mm9 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/target/Erg.1.tsv http:...//dbarchive.biosciencedbc.jp/kyushu-u/mm9/target/Erg.5.tsv http://dbarchive.biosciencedbc.jp/kyus...hu-u/mm9/target/Erg.10.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/colo/Erg.Blood.tsv,http://dbarchiv...e.biosciencedbc.jp/kyushu-u/mm9/colo/Erg.Prostate.tsv http://dbarchive.bioscience...dbc.jp/kyushu-u/mm9/colo/Blood.gml,http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/colo/Prostate.gml ...

Lifestyle / Tuuli Köller, Katrin Koov

Index Scriptorium Estoniae

Köller, Tuuli

2005-01-01

13.-17. X 2004 Jõesuus Põhjamaade Ehitusakadeemia V Sügispäevade raames toimunud rahvusvahelisest workshop'ist "Lifestyle", mille eestipoolne põhikorraldaja oli AB Sadakond, kaasa aitas Kavakava, toetas Eesti Kunstiakadeemia. Osalesid arhitektid, kunstnikud, arhitektuuri- ja kunstiüliõpilased Soomest, Rootsist, Saksamaalt ja Itaaliast. Keskenduti kolhoosiarhitektuurile. Katrin Koovi, Siiri Vallneri ja Kaire Nõmme, Rene Valneri ja Kalle Komissarovi jt. töödest

Kalalaev Katrin jääbki kadunuks / Kadi Laid

Index Scriptorium Estoniae

Laid, Kadi, 1976-

2003-01-01

Politsei lõpetab kalalaeva Katrin huku uurimise, kuna vaatamata korduvatele sukeldumistele, ei ole suudetud laevavrakki leida. Laeva kindlustanud Bico-Leks Kindlustuse AS-i järglane ERGO Kindlustus peab omanikule kindlustusraha välja maksma

A pulsed, mono-energetic and angular-selective UV photo-electron source for the commissioning of the KATRIN experiment

Energy Technology Data Exchange (ETDEWEB)

Behrens, J. [Institut fuer Kernphysik, WWU Muenster, Muenster (Germany); Karlsruhe Institute of Technology, IEKP, Eggenstein-Leopoldshafen (Germany); Ranitzsch, P.C.O.; Hannen, V.; Ortjohann, H.W.; Rest, O.; Winzen, D.; Zacher, M.; Weinheimer, C. [Institut fuer Kernphysik, WWU Muenster, Muenster (Germany); Beck, M. [Institut fuer Kernphysik, WWU Muenster, Muenster (Germany); Johannes-Gutenberg Universitaet, Institut fuer Physik, Mainz (Germany); Beglarian, A. [Karlsruhe Institute of Technology, IPE, Eggenstein-Leopoldshafen (Germany); Erhard, M.; Groh, S.; Kraus, M. [IEKP, Karlsruhe Institute of Technology, Eggenstein-Leopoldshafen (Germany); Schloesser, K.; Thuemmler, T. [Karlsruhe Institute of Technology, IKP, Karlsruhe (Germany); Valerius, K. [Institut fuer Kernphysik, WWU Muenster, Muenster (Germany); Karlsruhe Institute of Technology, IKP, Karlsruhe (Germany); Wierman, K.; Wilkerson, J.F. [University of North Carolina, Department of Physics and Astronomy, Chapel Hill, NC (United States)

2017-06-15

The KATRIN experiment aims to determine the neutrino mass scale with a sensitivity of 200 meV/c{sup 2} (90% C.L.) by a precision measurement of the shape of the tritium β-spectrum in the endpoint region. The energy analysis of the decay electrons is achieved by a MAC-E filter spectrometer. To determine the transmission properties of the KATRIN main spectrometer, a mono-energetic and angular-selective electron source has been developed. In preparation for the second commissioning phase of the main spectrometer, a measurement phase was carried out at the KATRIN monitor spectrometer where the device was operated in a MAC-E filter setup for testing. The results of these measurements are compared with simulations using the particle-tracking software ''Kassiopeia'', which was developed in the KATRIN collaboration over recent years. (orig.)

ERG induces epigenetic activation of Tudor domain-containing protein 1 (TDRD1) in ERG rearrangement-positive prostate cancer.

Science.gov (United States)

Kacprzyk, Lukasz A; Laible, Mark; Andrasiuk, Tatjana; Brase, Jan C; Börno, Stefan T; Fälth, Maria; Kuner, Ruprecht; Lehrach, Hans; Schweiger, Michal R; Sültmann, Holger

2013-01-01

Overexpression of ERG transcription factor due to genomic ERG-rearrangements defines a separate molecular subtype of prostate tumors. One of the consequences of ERG accumulation is modulation of the cell's gene expression profile. Tudor domain-containing protein 1 gene (TDRD1) was reported to be differentially expressed between TMPRSS2:ERG-negative and TMPRSS2:ERG-positive prostate cancer. The aim of our study was to provide a mechanistic explanation for the transcriptional activation of TDRD1 in ERG rearrangement-positive prostate tumors. Gene expression measurements by real-time quantitative PCR revealed a remarkable co-expression of TDRD1 and ERG (r(2) = 0.77) but not ETV1 (r(2)prostate cancer in vivo. DNA methylation analysis by MeDIP-Seq and bisulfite sequencing showed that TDRD1 expression is inversely correlated with DNA methylation at the TDRD1 promoter in vitro and in vivo (ρ = -0.57). Accordingly, demethylation of the TDRD1 promoter in TMPRSS2:ERG-negative prostate cancer cells by DNA methyltransferase inhibitors resulted in TDRD1 induction. By manipulation of ERG dosage through gene silencing and forced expression we show that ERG governs loss of DNA methylation at the TDRD1 promoter-associated CpG island, leading to TDRD1 overexpression. We demonstrate that ERG is capable of disrupting a tissue-specific DNA methylation pattern at the TDRD1 promoter. As a result, TDRD1 becomes transcriptionally activated in TMPRSS2:ERG-positive prostate cancer. Given the prevalence of ERG fusions, TDRD1 overexpression is a common alteration in human prostate cancer which may be exploited for diagnostic or therapeutic procedures.

Bernhard Linde. Noor-Eesti vooriülem. Bernhard Linde. Leader of the Young Estonian Pack

OpenAIRE

Jaanus Kulli

2012-01-01

Bernhard Linde (1886–1954) was a recognized and prolific Estonian theatre critic of the first quarter of the 20th century, who mediated and propagated western as well as eastern European theatrical innovations. In addition, he was active as a literary and art critic, publisher, and proponent of libraries, to a modest extent he was a prose writer and poet. Unquestionably, however, Bernhard Linde’s most prominent role was as one of the founding members of the literary movement Young Estonia. He...

Kunstnikud hindasid Eesti telekanalite uudistesaateid / Tarmo Luisk, Dan Mikkin, Katrin Kuldma

Index Scriptorium Estoniae

Luisk, Tarmo, 1970-

2011-01-01

Disainer Tarmo Luisk, graafik Dan Mikkin ja moekunstnik Katrin Kuldma hindasid Eesti telekanalite uudistesaateid "Aktuaalne kaamera" (ETV), "Reporter" (Kanal 2) ja "Seitsmesed uudised"(TV 3) esteetilisest vaatepunktist

Pärnu Kontserdimaja : Pärnu, Aida tn. 4 / Katrin Koov

Index Scriptorium Estoniae

Koov, Katrin, 1973-

2003-01-01

Projekteerija: COO Arhitektid. Arhitektid-sisekujundajad Hanno Grossschmidt, Kaire Nõmm, Katrin Koov. Konstruktor: Inseneribüroo Pike OÜ. Projekt: jaanuar 2002, valmis: november 2002. I ja II korruse plaan, 2 välis- ja 3 sisevaadet

Neli Peret Hispaanias, tekstiilikunstnikest rääkimata / Katrin Pere

Index Scriptorium Estoniae

Pere, Katrin, 1952-

1998-01-01

9. - 12. märtsini Barcelonas ja Madridis toimunud European Textile Networki aastakonverentsist. Eestist osalesid : Lylian Meister, Lea Pruuli, Aet Ollisaar-Kalamees, Katrin Pere, Merike Männi, Aune Taamal, Anne Tootma, Signe Kivi, Peeter Pere

Unustagem kõvaketas, kasutagem operatiivmälu! / Katrin Ruus

Index Scriptorium Estoniae

Ruus, Katrin

2008-01-01

Valik Mart Viljuse, Katrin Teesi, Piret Räni, Reimo Võsa-Tangsoo, Merle ja Erki Kannuse ning rühmituste Puhas Rõõm ja Infotankistid viimaste aastate töödest näituseprojektina "Operatiivmälu" Pärnu Kunstnike Maja galeriis ja Pärnu Linnagaleriis. 11 ill

Presidendi otsevalimine võib saada tegelikkuseks / Väino Linde

Index Scriptorium Estoniae

Linde, Väino

2003-01-01

Ilmunud ka Sakala (2003/Sep/18) lk. 2 ; Koit (2003/Sep/20) lk. 3 ; Vooremaa (2003/Sep/20) lk. 2 ; Pärnu Postimees (2003/Sep/20) lk. 15. Riigikogu põhiseaduskomisjoni liige Väino Linde presidendi otsevalimise seaduse eelnõust

Antibody-Based Detection of ERG Rearrangement-Positive Prostate Cancer

Directory of Open Access Journals (Sweden)

Kyung Park

2010-07-01

Full Text Available TMPRSS2-ERG gene fusions occur in 50% of prostate cancers and result in the overexpression of a chimeric fusion transcript that encodes a truncated ERG product. Previous attempts to detect truncated ERG products have been hindered by a lack of specific antibodies. Here, we characterize a rabbit anti-ERG monoclonal antibody (clone EPR 3864; Epitomics, Burlingame, CA using immunoblot analysis on prostate cancer cell lines, synthetic TMPRSS2-ERG constructs, chromatin immunoprecipitation, and immunofluorescence. We correlated ERG protein expression with the presence of ERG gene rearrangements in prostate cancertissues using a combined immunohistochemistry(IHC and fluorescence in situ hybridization (FISH analysis. We independently evaluated two patient cohorts and observed ERG expression confined to prostate cancer cells and high-grade prostatic intraepithelial reoplasia associated with ERG-positive cancer, as well as vessels and lymphocytes (where ERG has a known biologic role. Image analysis of 131 cases demonstrated nearly 100% sensitivity for detecting ERG rearrangement prostate cancer, with only 2 (1.5% of 131 cases demonstrating strong ERG protein expression without any known ERG gene fusion. The combired pathology evaluation of 207 patient tumors for ERG protein expression had 95.7% sensitivity and 96.5% specificity for determining ERG rearrangement prostate cancer. Ir conclusion, this study qualifies a specific anti-ERG antibody and demonstrates exquisite association between ERG gene rearrangement and truncated ERG protein product expression. Giver the ease of performing IHC versus FISH, ERG protein expression may be useful for molecularly subtypirg prostate cancer based or ERG rearrangement status and suggests clinical utility it prostate needle biopsy evaluation.

Sarnaneme ja eristume vormirõiva abiga / Britt Samoson ; kommenteerinud Katrin Kuldma

Index Scriptorium Estoniae

Samoson, Britt, 1982-

2010-01-01

Jaana Varkki ja Erkki Engso disainitud EXPO Shanghai 2010 maailmanäituse Eesti Paviljoni tiimitöötajate vormirõivastest. Rahvusooper Estonia ning Nokia kontserdimaja teenindajate rõivaid tutvustab nende looja Katrin Kuldma

Commissioning of the KATRIN Raman system for monitoring of the WGTS gas composition

Energy Technology Data Exchange (ETDEWEB)

Fischer, Sebastian; Bornschein, Beate; James, Timothy M.; Off, Andreas; Rupp, Simone; Seitz-Moskaliuk, Hendrik; Sturm, Michael; Wecker, Matthias [Karlsruhe Institute of Technology (Germany); Schloesser, Magnus [Universidad Complutense de Madrid (Spain); Karlsruhe Institute of Technology (Germany); Telle, Helmut H. [Universidad Complutense de Madrid (Spain)

2015-07-01

The Karlsruhe Tritium Neutrino (KATRIN) Experiment aims at determining the neutrino mass by the investigation of the endpoint energy-region of the tritium β-spectrum. Tritium in its molecular form ({sup 3}H{sub 2}) is injected into the Windowless Gaseous Tritium Source (WGTS) of KATRIN, and thus molecular effects, e.g. ro-vibrational excitations levels, have to be considered in the neutrino mass analysis in order to reach the design sensitivity of 200 meV/c{sup 2} (90% C.L.). As the source gas also contains impurities of the other hydrogen isotopes protium and deuterium - giving rise to different molecular excitation levels - continuous and precise monitoring of the source gas composition is required. Raman spectroscopy is the method of choice for this task as it is an inline and non-contact analysis method. In this talk, results from the recently performed commissioning phase of the KATRIN Raman system are presented: over the course of more than 50 days, consecutive Raman spectra (recorded with acquisition times of 60 s) of circulating tritium gas were acquired and analysed in real-time. In addition, valuable information on the system performance during long-term operation was gained.

ERG review of waste package corrosion mechanisms

International Nuclear Information System (INIS)

Geisert, R.E.

1988-01-01

The Engineering Review Group (ERG) was established by the Office of Nuclear Waste Isolation (ONWI) to help evaluate engineering-related issues in the US Department of Energy's nuclear waste repository program. The ERG reviewed the waste package corrosion mechanisms. This report documents the ERG's comments and recommendations on these subjects and the ONWI response to the specific points raised by the ERG. 1 ref

Solid electron sources for the energy scale monitoring in the KATRIN experiment

CERN Document Server

Zbořil, Miroslav; Vénos, D

The KArlsruhe TRItium Neutrino (KATRIN) experiment represents a next-generation tritium $\\beta$-decay experiment designed to perform a high precision direct measurement of the electron anti-neutrino mass m($\

Występowanie szarej pleśni tulipanow – Botrytis tulipae (Lib. Lind na plantacjach produkcyjnych [Botrytis tulipae (Lib. Lind in tulip plantations

Directory of Open Access Journals (Sweden)

Cz. Zamorski

2015-06-01

Full Text Available The incidence of disease caused by Botrytis tulipae (Lib. Lind was studied in selected tulip plantations. Primary and secondary infection, as well as infections of daughter bulbs were observed. The number of affected plants differed according (to the variety, season, and rainfall.

Ultra-stable implanted 83Rb/83mKr electron sources for the energy scale monitoring in the KATRIN experiment

CERN Document Server

Zboril, M.; Beck, M.; Bonn, J.; Dragoun, O.; Jakubek, J.; Johnston, K.; Kovalik, A.; Otten, E.W.; Schlösser, K.; Slezak, M.; Spalek, A.; Thümmler, T.; Venos, D.; Zemlicka, J.; Weinheimer, C.

2013-01-01

The KATRIN experiment aims at the direct model-independent determination of the average electron neutrino mass via the measurement of the endpoint region of the tritium beta decay spectrum. The electron spectrometer of the MAC-E filter type is used, requiring very high stability of the electric filtering potential. This work proves the feasibility of implanted 83Rb/83mKr calibration electron sources which will be utilised in the additional monitor spectrometer sharing the high voltage with the main spectrometer of KATRIN. The source employs conversion electrons of 83mKr which is continuously generated by 83Rb. The K-32 conversion line (kinetic energy of 17.8 keV, natural line width of 2.7 eV) is shown to fulfill the KATRIN requirement of the relative energy stability of +/-1.6 ppm/month. The sources will serve as a standard tool for continuous monitoring of KATRIN's energy scale stability with sub-ppm precision. They may also be used in other applications where the precise conversion lines can be separated fr...

Tähistaevata ela kui kotis / Tõnis Eenmäe, Katrin Jõgi

Index Scriptorium Estoniae

Eenmäe, Tõnis

2010-01-01

Astronoom Tõnis Eenmäe küsib ja vastab ülemäärase valgustatuse ehk valgusreostuse kohta: mõjust elukeskkonnale, mõõtmisviisid. Hugo Teffneri gümnaasiumi õpilase Katrin Jõgi kiri loodushuvilisele sõbrale valgusreostusest

Investigation of background processes in the KATRIN main spectrometer

Energy Technology Data Exchange (ETDEWEB)

Mueller, Axel [Karlsruhe Institute of Technology (KIT), Institut fuer Kernphysik (IKP) (Germany); Collaboration: KATRIN-Collaboration

2016-07-01

The KArlsruhe TRItium Neutrino experiment aims to probe the mass of the electron antineutrino in a model-independent way with an unsurpassed sensitivity of m{sub ν}=200 meV/c{sup 2} (90% C.L.). In order to determine the neutrino mass, the energy spectrum of electrons from the tritium β-decay is analyzed by a high-resolution electrostatic spectrometer which is based on the MAC-E filter principle. To keep the influence of the spectrometer background on the neutrino mass sensitivity small, KATRIN aims for a background level of 0.01 cps. For the investigation of different background components such as cosmic muons, external gamma radiation and the radioactive decay of isotopes in the volume of the spectrometer or on its surface, a series of dedicated measurements were performed with a combined system of main spectrometer and detector. This talk presents the results of measurements focusing on the secondary electron production at the inner surface of the spectrometer and compare them with electro-magnetic electron tracking simulations performed with the KATRIN developed simulation software KASSIOPEIA.

Expression of ERG Protein and TMRPSS2-ERG Fusion in Prostatic Carcinoma in Egyptian Patients

Directory of Open Access Journals (Sweden)

Ahmed Abdel-Hady

2017-03-01

CONCLUSION: Our findings emphasise that only malignant and pre-malignant cells and not benign cells from the prostate stain positive. ERG expression may offer a simpler, accurate and less costly alternative for evaluation of ERG fusion status in PCa.

Linde FUSRAP Site Remediation: Engineering Challenges and Solutions of Remedial Activities on an Active Industrial Facility - 13506

International Nuclear Information System (INIS)

Beres, Christopher M.; Fort, E. Joseph; Boyle, James D.

2013-01-01

The Linde FUSRAP Site (Linde) is located in Tonawanda, New York at a major research and development facility for Praxair, Inc. (Praxair). Successful remediation activities at Linde combines meeting cleanup objectives of radiological contamination while minimizing impacts to Praxair business operations. The unique use of Praxair's property coupled with an array of active and abandoned utilities poses many engineering and operational challenges; each of which has been overcome during the remedial action at Linde. The U.S. Army Corps of Engineers - Buffalo District (USACE) and CABRERA SERVICES, INC. (CABRERA) have successfully faced engineering challenges such as relocation of an aboveground structure, structural protection of an active water line, and installation of active mechanical, electrical, and communication utilities to perform remediation. As remediation nears completion, continued success of engineering challenges is critical as remaining activities exist in the vicinity of infrastructure essential to business operations; an electrical substation and duct bank providing power throughout the Praxair facility. Emphasis on engineering and operations through final remediation and into site restoration will allow for the safe and successful completion of the project. (authors)

Linde FUSRAP Site Remediation: Engineering Challenges and Solutions of Remedial Activities on an Active Industrial Facility - 13506

Energy Technology Data Exchange (ETDEWEB)

Beres, Christopher M.; Fort, E. Joseph [Cabrera Services, Inc., 473 Silver Lane, East Hartford, CT 06118 (United States); Boyle, James D. [United States Army Corps of Engineers - Buffalo, 1776 Niagara Street, Buffalo, NY 14207 (United States)

2013-07-01

The Linde FUSRAP Site (Linde) is located in Tonawanda, New York at a major research and development facility for Praxair, Inc. (Praxair). Successful remediation activities at Linde combines meeting cleanup objectives of radiological contamination while minimizing impacts to Praxair business operations. The unique use of Praxair's property coupled with an array of active and abandoned utilities poses many engineering and operational challenges; each of which has been overcome during the remedial action at Linde. The U.S. Army Corps of Engineers - Buffalo District (USACE) and CABRERA SERVICES, INC. (CABRERA) have successfully faced engineering challenges such as relocation of an aboveground structure, structural protection of an active water line, and installation of active mechanical, electrical, and communication utilities to perform remediation. As remediation nears completion, continued success of engineering challenges is critical as remaining activities exist in the vicinity of infrastructure essential to business operations; an electrical substation and duct bank providing power throughout the Praxair facility. Emphasis on engineering and operations through final remediation and into site restoration will allow for the safe and successful completion of the project. (authors)

Escitalopram block of hERG potassium channels.

Science.gov (United States)

Chae, Yun Ju; Jeon, Ji Hyun; Lee, Hong Joon; Kim, In-Beom; Choi, Jin-Sung; Sung, Ki-Wug; Hahn, Sang June

2014-01-01

Escitalopram, a selective serotonin reuptake inhibitor, is the pharmacologically active S-enantiomer of the racemic mixture of RS-citalopram and is widely used in the treatment of depression. The effects of escitalopram and citalopram on the human ether-a-go-go-related gene (hERG) channels expressed in human embryonic kidney cells were investigated using voltage-clamp and Western blot analyses. Both drugs blocked hERG currents in a concentration-dependent manner with an IC50 value of 2.6 μM for escitalopram and an IC50 value of 3.2 μM for citalopram. The blocking of hERG by escitalopram was voltage-dependent, with a steep increase across the voltage range of channel activation. However, voltage independence was observed over the full range of activation. The blocking by escitalopram was frequency dependent. A rapid application of escitalopram induced a rapid and reversible blocking of the tail current of hERG. The extent of the blocking by escitalopram during the depolarizing pulse was less than that during the repolarizing pulse, suggesting that escitalopram has a high affinity for the open state of the hERG channel, with a relatively lower affinity for the inactivated state. Both escitalopram and citalopram produced a reduction of hERG channel protein trafficking to the plasma membrane but did not affect the short-term internalization of the hERG channel. These results suggest that escitalopram blocked hERG currents at a supratherapeutic concentration and that it did so by preferentially binding to both the open and the inactivated states of the channels and by inhibiting the trafficking of hERG channel protein to the plasma membrane.

Indexing molecules for their hERG liability.

Science.gov (United States)

Rayan, Anwar; Falah, Mizied; Raiyn, Jamal; Da'adoosh, Beny; Kadan, Sleman; Zaid, Hilal; Goldblum, Amiram

2013-07-01

The human Ether-a-go-go-Related-Gene (hERG) potassium (K(+)) channel is liable to drug-inducing blockage that prolongs the QT interval of the cardiac action potential, triggers arrhythmia and possibly causes sudden cardiac death. Early prediction of drug liability to hERG K(+) channel is therefore highly important and preferably obligatory at earlier stages of any drug discovery process. In vitro assessment of drug binding affinity to hERG K(+) channel involves substantial expenses, time, and labor; and therefore computational models for predicting liabilities of drug candidates for hERG toxicity is of much importance. In the present study, we apply the Iterative Stochastic Elimination (ISE) algorithm to construct a large number of rule-based models (filters) and exploit their combination for developing the concept of hERG Toxicity Index (ETI). ETI estimates the molecular risk to be a blocker of hERG potassium channel. The area under the curve (AUC) of the attained model is 0.94. The averaged ETI of hERG binders, drugs from CMC, clinical-MDDR, endogenous molecules, ACD and ZINC, were found to be 9.17, 2.53, 3.3, -1.98, -2.49 and -3.86 respectively. Applying the proposed hERG Toxicity Index Model on external test set composed of more than 1300 hERG blockers picked from chEMBL shows excellent performance (Matthews Correlation Coefficient of 0.89). The proposed strategy could be implemented for the evaluation of chemicals in the hit/lead optimization stages of the drug discovery process, improve the selection of drug candidates as well as the development of safe pharmaceutical products. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

The cryogenic pumping section of KATRIN and the test experiment TRAP

CERN Document Server

Eichelhardt, F

2011-01-01

The Karlsruhe Tritium Neutrino experiment (KATRIN) employs a Cryogenic Pumping Section (CPS) at ~ 4.5 K to suppress the tritium penetration into the spectrometers. A test experiment (TRAP - Tritium Argon frost Pump) has been set up to investigate the tritium pumping performance of the CPS.

Alan Guth and Andrei Linde win international cosmology award

CERN Multimedia

2004-01-01

"Leading theoretical cosmologists Alan Guth, Weisskopf Professor of Physics at the Massachusetts Institute of Technology, and Andrei Linde, Professor of Physics at Stanford University, who played prominent roles in developing and refining the theory of cosmic inflation, have been selected by an international panel of experts to receive the 2004 Cosmology Prize of the Peter Gruber Foundation" (1 page).

Kuu plaat : Lauri Saatpalu ja Katrin Mandel "Sa oled hea". Plaadid kauplusest Lasering

Index Scriptorium Estoniae

2005-01-01

Heliplaatidest: Lauri Saatpalu ja Katrin Mandel "Sa oled hea", Goldfrapp "Supernature", Ultima Thule "Ingel ja suli", Sigur Ros "Takk...", Franz Ferdinand "You Could Have It So Much Better", Ans.Andur "Tuled peale"

Monitoring of the energy scale in the KATRIN neutrino experiment

CERN Document Server

AUTHOR|(CDS)2083282

The question of the absolute mass scale of neutrinos is of particular interest for particle physics, astrophysics, and cosmology. The KATRIN experiment (KArlsruhe TRItium Neutrino experiment) aims to address the effective electron antineutrino mass from the shape of the tritium $\\beta$-spectrum with an unprecedented sensitivity of 0.2 eV/c$^2$. One of the major systematic effects concerns the experimental energy scale, which has to be stable at the level of only a few parts in a million. For its calibration and monitoring the monoenergetic electrons emitted in the internal conversion of $\\gamma$-transition of the metastable isotope $^{83\\mathrm{m}}$Kr will be extensively applied. The aim of this thesis is to address the problem of KATRIN energy scale distortions and its monitoring in detail. The source of electrons based on $^{83\\mathrm{m}}$Kr embedded in a solid as well as the source based on gaseous $^{83\\mathrm{m}}$Kr are studied. Based on the experimental results an approach for the continuous stability m...

La transformation économique de l'Inde favorise-t-elle l ...

International Development Research Centre (IDRC) Digital Library (Canada)

La transformation économique de l'Inde favorise-t-elle l'autonomisation ... sur les plans social et économique, il peut arriver que la participation des femmes à la vie ... Related content. Call for proposals for three Asian market-entry studies.

Gaseous 83mKr generator for KATRIN

Science.gov (United States)

Sentkerestiová, J.; Dragoun, O.; Lebeda, O.; Ryšavý, M.; Sturm, M.; Vénos, D.

2018-04-01

Monoenergetic conversion electrons from the 83mKrKr isomeric state have been proven to be useful in the calibration of several tritium neutrino mass and dark matter experiments. In this paper the design and characteristics of the gaseous 83mKrKr generator, including the 83Rb/83mKrKr source behavior in tritium, for the KATRIN experiment are presented. Using Si(Li) and silicon drift detectors (SDD) detectors, the half-life of the 83mKrKr isomeric state was measured to be 1.8620 ± 0.0019 h.

Mechanisms underlying probucol-induced hERG-channel deficiency

Directory of Open Access Journals (Sweden)

Shi YQ

2015-07-01

Full Text Available Yuan-Qi Shi,1,* Cai-Chuan Yan,1,* Xiao Zhang,1 Meng Yan,1 Li-Rong Liu,1 Huai-Ze Geng,1 Lin Lv,1 Bao-Xin Li1,21Department of Pharmacology, Harbin Medical University, 2State-Province Key Laboratory of Biopharmaceutical Engineering, Harbin, Heilongjiang, People’s Republic of China*These authors contributed equally to this workAbstract: The hERG gene encodes the pore-forming α-subunit of the rapidly activating delayed rectifier potassium channel (IKr, which is important for cardiac repolarization. Reduction of IhERG due to genetic mutations or drug interferences causes long QT syndrome, leading to life-threatening cardiac arrhythmias (torsades de pointes or sudden death. Probucol is a cholesterol-lowering drug that could reduce hERG current by decreasing plasma membrane hERG protein expression and eventually cause long QT syndrome. Here, we investigated the mechanisms of probucol effects on IhERG and hERG-channel expression. Our data demonstrated that probucol reduces SGK1 expression, known as SGK isoform, in a concentration-dependent manner, resulting in downregulation of phosphorylated E3 ubiquitin ligase Nedd4-2 expression, but not the total level of Nedd4-2. As a result, the hERG protein reduces, due to the enhanced ubiquitination level. On the contrary, carbachol could enhance the phosphorylation level of Nedd4-2 as an alternative to SGK1, and thus rescue the ubiquitin-mediated degradation of hERG channels caused by probucol. These discoveries provide a novel mechanism of probucol-induced hERG-channel deficiency, and imply that carbachol or its analog may serve as potential therapeutic compounds for the handling of probucol cardiotoxicity.Keywords: long QT, hERG potassium channels, probucol, SGK1, Nedd4-2

ERG oncoprotein expression in prostate carcinoma patients of different ethnicities.

Science.gov (United States)

Kelly, Gregory M; Kong, Yink Heay; Dobi, Albert; Srivastava, Shiv; Sesterhenn, Isabell A; Pathmanathan, Rajadurai; Tan, Hui Meng; Tan, Shyh-Han; Cheong, Sok Ching

2015-01-01

Overexpression of the erythroblast transformation-specific-related gene (ERG) oncoprotein due to transmembrane protease, serine 2 ( TMPRSS2 ) -ERG fusion, the most prevalent genomic alteration in prostate cancer (CaP), is more frequently observed among Caucasian patients compared to patients of African or Asian descent. To the best of our knowledge, this is the first study to investigate the prevalence of ERG alterations in a multiethnic cohort of CaP patients. A total of 191 formalin-fixed paraffin-embedded sections of transrectal ultrasound-guided prostate biopsy specimens, collected from 120 patients treated at the Sime Darby Medical Centre, Subang Jaya, Malaysia, were analyzed for ERG protein expression by immunohistochemistry using the anti-ERG monoclonal antibody 9FY as a surrogate for the detection of ERG fusion events. The overall frequency of ERG protein expression in the population evaluated in this study was 39.2%. Although seemingly similar to rates reported in other Asian communities, the expression of ERG was distinct amongst different ethnic groups (P=0.004). Malaysian Indian (MI) patients exhibited exceedingly high expression of ERG in their tumors, almost doubling that of Malaysian Chinese (MC) patients, whereas ERG expression was very low amongst Malay patients (12.5%). When collectively analyzing data, we observed a significant correlation between younger patients and higher ERG expression (P=0.04). The prevalence of ERG expression was significantly different amongst CaP patients of different ethnicities. The higher number of ERG-expressing tumors among MI patients suggested that the TMPRSS2-ERG fusion may be particularly important in the pathogenesis of CaP amongst this group of patients. Furthermore, the more frequent expression of ERG among the younger patients analyzed suggested an involvement of ERG in the early onset of CaP. The results of this study underline the value of using ERG status to better understand the differences in the

Twilio Eesti büroo = Offices of Twilio Estonia / Katrin Kaevats ; kommenteerinud Ann Koljang

Index Scriptorium Estoniae

Kaevats, Katrin, 1980-

2016-01-01

Rahvusvahelise ettevõtte Twilio Eesti büroo Tallinnas, Veerenni tn. 24. Sisekujunduse autorid Katrin Kaevats, Jaan Port, Markus Nimik, Neeme Tiimus, Anna Nikland. Büroohoone projekteerisid PIN Arhitektid

Fracture toughness master curve characterization of Linde 1092 weld metal for Beaver valley 1 reactor

International Nuclear Information System (INIS)

Lee, Bong Sang; Yang, Won Jon; Hong, Jun Hwa

2000-12-01

This report summarizes the test results obtained from the Korean contribution to the integrity assessment of low toughness Beaver Valley reactor vessel by characterizing the fracture toughness of Linde 1092 (No. 305414) weld metal. 10 PCVN specimens and 10 1T-CT specimens were tested in accordance with the ASTM E 1921-97 standard, 'Standard test method for determination of reference temperature, T o , for ferritic steels in the transition range'. This results can also be useful for assessment of Linde 80 low toughness welds of Kori-1

Fracture toughness master curve characterization of Linde 1092 weld metal for Beaver valley 1 reactor

Energy Technology Data Exchange (ETDEWEB)

Lee, Bong Sang; Yang, Won Jon; Hong, Jun Hwa

2000-12-01

This report summarizes the test results obtained from the Korean contribution to the integrity assessment of low toughness Beaver Valley reactor vessel by characterizing the fracture toughness of Linde 1092 (No. 305414) weld metal. 10 PCVN specimens and 10 1T-CT specimens were tested in accordance with the ASTM E 1921-97 standard, 'Standard test method for determination of reference temperature, T{sub o}, for ferritic steels in the transition range'. This results can also be useful for assessment of Linde 80 low toughness welds of Kori-1.

Modulation of ERG channels by XE991

DEFF Research Database (Denmark)

Elmedyb, Pernille; Calloe, Kirstine; Schmitt, Nicole

2007-01-01

In neuronal tissue, KCNQ2-5 channels conduct the physiologically important M-current. In some neurones, the M-current may in addition be conducted partly by ERG potassium channels, which have widely overlapping expression with the KCNQ channel subunits. XE991 and linopiridine are known to be stan......In neuronal tissue, KCNQ2-5 channels conduct the physiologically important M-current. In some neurones, the M-current may in addition be conducted partly by ERG potassium channels, which have widely overlapping expression with the KCNQ channel subunits. XE991 and linopiridine are known...... to be standard KCNQ potassium channel blockers. These compounds have been used in many different tissues as specific pharmacological tools to discern native currents conducted by KCNQ channels from other potassium currents. In this article, we demonstrate that ERG1-2 channels are also reversibly inhibited by XE......991 in the micromolar range (EC(50) 107 microM for ERG1). The effect has been characterized in Xenopus laevis oocytes expressing ERG1-2 and in the mammalian HEK293 cell line stably expressing ERG1 channels. The IC(50) values for block of KCNQ channels by XE991 range 1-65 microM. In conclusion, great...

Current State of ERG as Biomarker in Prostatic Adenocarcinoma.

Science.gov (United States)

Acs, Balazs; Szarvas, Tibor; Szekely, Nora; Nyirady, Peter; Szasz, A Marcell

2015-01-01

In this review we briefly discuss the possible biomarkers of prostate cancer among them we focus and analyze the relevance of TMPRSS2-ERG fusion gene in line with ERG expression in the diagnosis of prostate cancer. Starting at diagnosis and genetic alterations in prostate carcinomas, we examine the incidence and detection of the most common genetic aberration in this tumor and its protein product as well. We also examined the correlation of clinicopathological factors and prognosis with ERG and the TMPRSS2-ERG fusion oncogene and ERG expression as predictive markers.

Deletion of the Candida glabrata ERG3 and ERG11 genes: effect on cell viability, cell growth, sterol composition, and antifungal susceptibility.

Science.gov (United States)

Geber, A; Hitchcock, C A; Swartz, J E; Pullen, F S; Marsden, K E; Kwon-Chung, K J; Bennett, J E

1995-01-01

We have cloned and sequenced the structural genes encoding the delta 5,6 sterol desaturase (ERG3 gene) and the 14 alpha-methyl sterol demethylase (ERG11 gene) from Candida glabrata L5 (leu2). Single and double mutants of these genes were created by gene deletion. The phenotypes of these mutants, including sterol profiles, aerobic viabilities, antifungal susceptibilities, and generation times, were studied. Strain L5D (erg3 delta::LEU2) accumulated mainly ergosta-7,22-dien-3 beta-ol, was aerobically viable, and remained susceptible to antifungal agents but had a slower generation time than its parent strain. L5LUD (LEU2 erg11 delta::URA3) strains required medium supplemented with ergosterol and an anaerobic environment for growth. A spontaneous aerobically viable mutant, L5LUD40R (LEU erg11 delta::URA3), obtained from L5LUD (LEU2 erg11 delta::URA3), was found to accumulate lanosterol and obtusifoliol, was resistant to azole antifungal agents, demonstrated some increase in resistance to amphotericin B, and exhibited a 1.86-fold increase in generation time in comparison with L5 (leu2). The double-deletion mutant L5DUD61 (erg3 delta::LEU2 erg11 delta::URA3) was aerobically viable, produced mainly 14 alpha-methyl fecosterol, and had the same antifungal susceptibility pattern as L5LUD40R (LEU2 erg11 delta::URA3), and its generation time was threefold greater than that of L5 (leu2). Northern (RNA) analysis revealed that the single-deletion mutants had a marked increase in message for the undeleted ERG3 and ERG11 genes. These results indicate that differences in antifungal susceptibilities and the restoration of aerobic viability exist between the C. glabrata ergosterol mutants created in this study and those sterol mutants with similar genetic lesions previously reported for Saccharomyces cerevisiae. PMID:8593007

Reduced Erg Dosage Impairs Survival of Hematopoietic Stem and Progenitor Cells.

Science.gov (United States)

Xie, Ying; Koch, Mia Lee; Zhang, Xin; Hamblen, Melanie J; Godinho, Frank J; Fujiwara, Yuko; Xie, Huafeng; Klusmann, Jan-Henning; Orkin, Stuart H; Li, Zhe

2017-07-01

ERG, an ETS family transcription factor frequently overexpressed in human leukemia, has been implicated as a key regulator of hematopoietic stem cells. However, how ERG controls normal hematopoiesis, particularly at the stem and progenitor cell level, and how it contributes to leukemogenesis remain incompletely understood. Using homologous recombination, we generated an Erg knockdown allele (Erg kd ) in which Erg expression can be conditionally restored by Cre recombinase. Erg kd/kd animals die at E10.5-E11.5 due to defects in endothelial and hematopoietic cells, but can be completely rescued by Tie2-Cre-mediated restoration of Erg in these cells. In Erg kd/+ mice, ∼40% reduction in Erg dosage perturbs both fetal liver and bone marrow hematopoiesis by reducing the numbers of Lin - Sca-1 + c-Kit + (LSK) hematopoietic stem and progenitor cells (HSPCs) and megakaryocytic progenitors. By genetic mosaic analysis, we find that Erg-restored HSPCs outcompete Erg kd/+ HSPCs for contribution to adult hematopoiesis in vivo. This defect is in part due to increased apoptosis of HSPCs with reduced Erg dosage, a phenotype that becomes more drastic during 5-FU-induced stress hematopoiesis. Expression analysis reveals that reduced Erg expression leads to changes in expression of a subset of ERG target genes involved in regulating survival of HSPCs, including increased expression of a pro-apoptotic regulator Bcl2l11 (Bim) and reduced expression of Jun. Collectively, our data demonstrate that ERG controls survival of HSPCs, a property that may be used by leukemic cells. Stem Cells 2017;35:1773-1785. © 2017 AlphaMed Press.

Stability measurements of the electron gun for the KATRIN rear section

Energy Technology Data Exchange (ETDEWEB)

Ebenhoech, Sylvia [Karlsruhe Institute of Technology (KIT) (Germany). Institute for Technical Physics (ITEP), Tritium Laboratory Karlsruhe (TLK); Collaboration: KATRIN-Collaboration

2016-07-01

The aim of the KArlsruhe TRItium Neutrino (KATRIN) experiment is to determine the antineutrino mass with a sensitivity of 0.2 eV (90 % C.L.) by high-precision spectroscopy close to the tritium beta decay endpoint at 18.6 keV. To achieve the sensitivity aim both statistical and systematic uncertainties must be minimized. One contribution to the systematic error are uncertainties in the column density of the tritium source or in the source activity. In order to detect and monitor changes in the tritium source the Rear Section, which is integrated at the rear end of the KATRIN setup, is used. The Rear Section includes an angular selective electron gun (e-gun) based on the photoelectric effect. With the e-gun it will be possible e.g. to achieve a precise calibration of the column source density. To achieve the requirements on the e-gun a stable UV light source is essential to produce photoelectrons. The presentation focuses on the setup of the e-gun and intensity stability measurements of the UV light source setup.

Activation of ERG2 potassium channels by the diphenylurea NS1643

DEFF Research Database (Denmark)

Elmedyb, Pernille; Olesen, Søren-Peter; Grunnet, Morten

2007-01-01

Three members of the ERG potassium channel family have been described (ERG1-3 or Kv 11.1-3). ERG1 is by far the best characterized subtype and it constitutes the molecular component of the cardiac I(Kr) current. All three channel subtypes are expressed in neurons but their function remains unclear....... The lack of functional information is at least partly due to the lack of specific pharmacological tools. The compound NS1643 has earlier been reported as an ERG1 channel activator. We found that NS1643 also activates the ERG2 channel; however, the molecular mechanism of the activation differs between...... the ERG1 and ERG2 channels. This is surprising since ERG1 and ERG2 channels have very similar biophysical and structural characteristics. For ERG2, NS1643 causes a left-ward shift of the activation curve, a faster time-constant of activation and a slower time-constant of inactivation as well...

High Glucose Represses hERG K+ Channel Expression through Trafficking Inhibition

Directory of Open Access Journals (Sweden)

Yuan-Qi Shi

2015-08-01

Full Text Available Background/Aims: Abnormal QT prolongation is the most prominent cardiac electrical disturbance in patients with diabetes mellitus (DM. It is well known that the human ether-ago-go-related gene (hERG controls the rapid delayed rectifier K+ current (IKr in cardiac cells. The expression of the hERG channel is severely down-regulated in diabetic hearts, and this down-regulation is a critical contributor to the slowing of repolarization and QT prolongation. However, the intracellular mechanisms underlying the diabetes-induced hERG deficiency remain unknown. Methods: The expression of the hERG channel was assessed via western blot analysis, and the hERG current was detected with a patch-clamp technique. Results: The results of our study revealed that the expression of the hERG protein and the hERG current were substantially decreased in high-glucose-treated hERG-HEK cells. Moreover, we demonstrated that the high-glucose-mediated damage to the hERG channel depended on the down-regulation of protein levels but not the alteration of channel kinetics. These discoveries indicated that high glucose likely disrupted hERG channel trafficking. From the western blot and immunoprecipitation analyses, we found that high glucose induced trafficking inhibition through an effect on the expression of Hsp90 and its interaction with hERG. Furthermore, the high-glucose-induced inhibition of hERG channel trafficking could activate the unfolded protein response (UPR by up-regulating the expression levels of activating transcription factor-6 (ATF-6 and the ER chaperone protein calnexin. In addition, we demonstrated that 100 nM insulin up-regulated the expression of the hERG channel and rescued the hERG channel repression caused by high glucose. Conclusion: The results of our study provide the first evidence of a high-glucose-induced hERG channel deficiency resulting from the inhibition of channel trafficking. Furthermore, insulin promotes the expression of the hERG channel

The multifocal electroretinogram (mfERG) in the pig

DEFF Research Database (Denmark)

Voss Kyhn, Maria; Kiilgaard, Jens Folke; Lopez, Ana Garcia

2007-01-01

To establish a method allowing multifocal electroretinography (mfERG) recording with simultaneous fundus monitoring on anaesthetized pigs. In addition we characterize the peaks of the porcine mfERG trace, and compare the visual streak area with the optic nerve head, a known non-response area....... Finally we illustrate the feasibility of the method by performing mfERG after an induced laser burn in the visual streak....

Precision monitoring and calibration of the high-voltage for the KATRIN experiment; Praezisionsueberwachung und Kalibration der Hochspannung fuer das KATRIN-Experiment

Energy Technology Data Exchange (ETDEWEB)

Thuemmler, T.

2007-11-12

The goal of the KATRIN(KArlsruhe TRIritium Neutrino) Experiment is to directly determine the neutrino rest mass from the kinematics of the tritium-{beta}-decay. KATRIN uses the high resolution and luminosity of a spectrometer following the MAC-E filter principle. Based on the experience of the successful predecessor experiments in Mainz and Troisk and the improved experimental technology, KATRIN aims to reach a sensitivity on the neutrino mass of 0.2 eV/c{sup 2} (90% C.L.). One of the few systematic uncertainties that have to be reduced to meet this goal is the uncertainty of measuring and monitoring the potential of the electrostatic filter of the spectrometer. In tritium measurement mode voltages of about U{sub 0} =-18.6 kV have to be permanently monitored with a maximum uncertainty of 3.3 ppm ({approx} 61mV at U{sub 0}), in order not to add more than {delta}m{sup 2}{sub {nu}{sub ec}}{sup 4} {<=} 0.0075 eV{sup 2} to the total systematic uncertainty. The goal of this work is to build a new precision high voltage divider in cooperation with PTB Braunschweig that reaches an uncertainty of about 1 ppm at voltages up to 35 kV. The divider is based on a new type of precision resistors, which have been screened with respect to their warm up drift and their temperature coefficient at the ppm level. By combining 100 of the best matching samples, the mutual warm up effect could be reduced to a computed value of <0.02 ppm. The precision resistors are mounted in a shielded and temperature stabilized vessel under N{sub 2} gas. The properties of both installed low voltage outputs with the ratios 1972:1 and 3944:1 have been repeatedly calibrated with about one year time difference at the DC high voltage laboratory (division 2.31) of PTB. The performance of the new divider in real measurements has been tested with the prototype of the new condensed {sup 83m}Kr calibration source (CKrS) [Ost08] at the Mainz spectrometer. Detailed stability investigations of the energy of the {sup

Missugused on teie kogemused väikeklassidega? / Villu Mengel, Ana Kontor, Katrin Betlem, Riina Kink

Index Scriptorium Estoniae

2013-01-01

Küsimusele vastasid Sikupilli keskkooli direktor Villu Mengel, Tartu hariduse tugiteenuste keskuse eripedagoog Ana Kontor, Tabasalu ühisgümnaasiumi õppejuht-sotsiaalpedagoog Katrin Betlem, Keila kooli põhikooli õppejuht Riina Kink

ERG review of waste package container materials selection and corrosion

International Nuclear Information System (INIS)

Moak, D.P.; Perrin, J.S.

1986-07-01

The Engineering Review Group (ERG) was established by the Office of Nuclear Waste Isolation (ONWI) to help evaluate engineering-related issues in the US Department of Energy's nuclear waste repository program. The October 1984 meeting of the ERG reviewed the waste package container materials selection and corrosion. This report documents the ERG's comments and recommendations on these subjects and the ONWI response to the specific points raised by the ERG

V Las-Vegas so statujei Svobodõ / Katrin Sangla, Gerly Tinn, Tamara Korjagina ; interv. Alina Zelimhanova

Index Scriptorium Estoniae

Sangla, Katrin

2002-01-01

Küsitletakse soengukunsti maailmameistrivõistlustel Hair World 2002 Las-Vegases osalenud juuksur Tamara Korjaginat, jumestuskunstnik Katrin Sanglat ja moekunstnik Gerly Tinni võistluse kohta. Saavutasid võiskondlikus arvestuses kolmanda koha

hERG trafficking inhibition in drug-induced lethal cardiac arrhythmia.

Science.gov (United States)

Nogawa, Hisashi; Kawai, Tomoyuki

2014-10-15

Acquired long QT syndrome induced by non-cardiovascular drugs can cause lethal cardiac arrhythmia called torsades de points and is a significant problem in drug development. The prolongation of QT interval and cardiac action potential duration are mainly due to reduced physiological function of the rapidly activating voltage-dependent potassium channels encoded by human ether-a-go-go-related gene (hERG). Structurally diverse groups of drugs are known to directly inhibit hERG channel conductance. Therefore, the ability of acute hERG inhibition is routinely assessed at the preclinical stages in pharmaceutical testing. Recent findings indicated that chronic treatment with various drugs not only inhibits hERG channels but also decreases hERG channel expression in the plasma membrane of cardiomyocytes, which has become another concern in safety pharmacology. The mechanisms involve the disruption of hERG trafficking to the surface membrane or the acceleration of hERG protein degradation. From this perspective, we present a brief overview of mechanisms of drug-induced trafficking inhibition and pathological regulation. Understanding of drug-induced hERG trafficking inhibition may provide new strategies for predicting drug-induced QT prolongation and lethal cardiac arrhythmia in pharmaceutical drug development. Copyright © 2014 Elsevier B.V. All rights reserved.

Naised, kes toovad naeratuse näole / Katrin Oja

Index Scriptorium Estoniae

Oja, Katrin

2006-01-01

Heast teenindusest räägivad Eesti Gaasi juhatuse esimehe assistent, Aasta Sekretär 2005 Tiivi Lind, lounge 8 baaridaam Kadri Kask ja Sampo Panga koolitusspetsialist, Aasta Teenindaja 2006 Aires Rühka. Kommenteerivad nende ülemused - Sampo Panga koolitusosakonna juhataja Külli Meier, Eesti Gaasi juhatuse esimees Aarne Saar ja lounge 8 mänedžer Heinar Õispuu

Jutuvõistluse "Musta mantliga mees" võitis Katrin Johanson

Index Scriptorium Estoniae

2007-01-01

Eduard Vilde muuseumi poolt läbi viidud krimi- ja põnevusjuttude võistlusest "Musta mantliga mees". Žürii: Karl Martin Sinijärv, Juhan Habicht, Paul Pajos, Rebekka Lotman, Kristin Rammus, Piret Meos.Võitja: Katrin Johanson, teine koht: Taavet Kase, kolmas koht: Imre Kõuts. Ajalehe "Postimees" eriauhinnad said: Juhan Voolaid, Hella Riisalu, Stina Maria Vilt, Sirle Poikkanen, Märt Kivimäe. Tallinna noorte infokeskuse auhinnad: Juhan Voolaid, Sirle Poikkalainen, Lilli Anderson, Aino Rätsep. Eduard Vilde muuseumi eriauhinnad: Merilin Jürjo, Laura Pirso

Ettevõtted panustavad eelarve koostamisel järjest enam spetsialistide täiendkoolitusse / Madli Kents

Index Scriptorium Estoniae

Kents, Madli

2005-01-01

AS-i Kalev koolitusspetsialist Gerli Jõgi, Hansapanga koolituse ostujuht Katrin Kase ja AS-i Eesti Energia koolitusjuht Erge Heido selgitavad, millele pööratakse tähelepanu nende ettevõttes koolituseelarve koostamisel ning annavad ülevaate rakendatavatest koolitusvormidest. Vt. samas: Marja Liis. Esiplaanil on teenindajad

Mechanism and pharmacological rescue of berberine-induced hERG channel deficiency

Science.gov (United States)

Yan, Meng; Zhang, Kaiping; Shi, Yanhui; Feng, Lifang; Lv, Lin; Li, Baoxin

2015-01-01

Berberine (BBR), an isoquinoline alkaloid mainly isolated from plants of Berberidaceae family, is extensively used to treat gastrointestinal infections in clinics. It has been reported that BBR can block human ether-a-go-go-related gene (hERG) potassium channel and inhibit its membrane expression. The hERG channel plays crucial role in cardiac repolarization and is the target of diverse proarrhythmic drugs. Dysfunction of hERG channel can cause long QT syndrome. However, the regulatory mechanisms of BBR effects on hERG at cell membrane level remain unknown. This study was designed to investigate in detail how BBR decreased hERG expression on cell surface and further explore its pharmacological rescue strategies. In this study, BBR decreases caveolin-1 expression in a concentration-dependent manner in human embryonic kidney 293 (HEK293) cells stably expressing hERG channel. Knocking down the basal expression of caveolin-1 alleviates BBR-induced hERG reduction. In addition, we found that aromatic tyrosine (Tyr652) and phenylalanine (Phe656) in S6 domain mediate the long-term effect of BBR on hERG by using mutation techniques. Considering both our previous and present work, we propose that BBR reduces hERG membrane stability with multiple mechanisms. Furthermore, we found that fexofenadine and resveratrol shorten action potential duration prolongated by BBR, thus having the potential effects of alleviating the cardiotoxicity of BBR. PMID:26543354

ERG2 and ERG24 Are Required for Normal Vacuolar Physiology as Well as Candida albicans Pathogenicity in a Murine Model of Disseminated but Not Vaginal Candidiasis.

Science.gov (United States)

Luna-Tapia, Arturo; Peters, Brian M; Eberle, Karen E; Kerns, Morgan E; Foster, Timothy P; Marrero, Luis; Noverr, Mairi C; Fidel, Paul L; Palmer, Glen E

2015-10-01

Several important classes of antifungal agents, including the azoles, act by blocking ergosterol biosynthesis. It was recently reported that the azoles cause massive disruption of the fungal vacuole in the prevalent human pathogen Candida albicans. This is significant because normal vacuolar function is required to support C. albicans pathogenicity. This study examined the impact of the morpholine antifungals, which inhibit later steps of ergosterol biosynthesis, on C. albicans vacuolar integrity. It was found that overexpression of either the ERG2 or ERG24 gene, encoding C-8 sterol isomerase or C-14 sterol reductase, respectively, suppressed C. albicans sensitivity to the morpholines. In addition, both erg2Δ/Δ and erg24Δ/Δ mutants were hypersensitive to the morpholines. These data are consistent with the antifungal activity of the morpholines depending upon the simultaneous inhibition of both Erg2p and Erg24p. The vacuoles within both erg2Δ/Δ and erg24Δ/Δ C. albicans strains exhibited an aberrant morphology and accumulated large quantities of the weak base quinacrine, indicating enhanced vacuolar acidification compared with that of control strains. Both erg mutants exhibited significant defects in polarized hyphal growth and were avirulent in a mouse model of disseminated candidiasis. Surprisingly, in a mouse model of vaginal candidiasis, both mutants colonized mice at high levels and induced a pathogenic response similar to that with the controls. Thus, while targeting Erg2p or Erg24p alone could provide a potentially efficacious therapy for disseminated candidiasis, it may not be an effective strategy to treat vaginal infections. The potential value of drugs targeting these enzymes as adjunctive therapies is discussed. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Intrafocal heterogeneity of ERG protein expression and gene fusion pattern in prostate cancer.

Science.gov (United States)

Suh, Ja Hee; Park, Jeong Hwan; Lee, Cheol; Moon, Kyung Chul

2017-10-01

Prostate cancer is considered to be highly heterogeneous, with various morphologic features and biologic behaviors. The TMPRSS2-ERG gene fusion is the most frequently observed genetic aberration in prostate cancer. The aim of this study was to elucidate the intrafocal heterogeneity of ERG gene fusion status. ERG immunohistochemistry (IHC) was performed in samples from 168 prostate cancer patients who had undergone radical prostatectomy, and 40 cases showing ERG-positive IHC staining were selected for tissue microarray (TMA) construction. Two to six representative cores were selected from each tumor focus. In the cases with heterogeneous ERG IHC staining intensity, the areas showing different intensities were separately selected. Using the TMA blocks, IHC and fluorescence in situ hybridization (FISH) were conducted to evaluate the heterogeneity of ERG protein expression and ERG fusion gene patterns, respectively, in a single tumor focus. Heterogeneity of ERG IHC staining was defined as the simultaneous presence of negative and positive cores in the same tumor focus. Heterogeneity of ERG FISH was defined by the presence of cores with positive and negative FISH signals or cores with break-apart and interstitial deletion FISH signals in the same tumor focus. A total of 202 TMA cores were isolated from 40 ERG-positive cases. Of the 202 total cores, 19 were negative for ERG IHC staining, and 46 showed 1+, 52 showed 2+, and 85 showed 3+ ERG staining intensity. Eleven cores were negative for ERG FISH signal, 119 cores showed ERG break-apart FISH signals, and the remaining 72 cores revealed interstitial deletion. Intrafocal heterogeneity of ERG IHC staining was found in 20% (8/40) of cases, and intrafocal heterogeneity of ERG gene fusion pattern was found in 32.5% (13/40) of cases. In summary, this study showed significantly frequent intrafocal heterogeneity of ERG protein expression, gene fusion status and fusion pattern. This heterogeneity can be caused by the development

Low capacity Linde-Hampson nitrogen liquefier

International Nuclear Information System (INIS)

Hedegard, K.; Atkins, E.; Walker, G.

1990-01-01

A closed-cycle Linde-Hampson nitrogen liquefier was developed incorporating a new, non-clogging, demand flow Joule-Thomson nozzle. The flow area of the nozzle, a tapered annular orifice, is regulated by a very rugged load-sensitive differential thermal expansion scheme and by a manually adjustable micrometer mechanism. Labyrinth flow spoilers within the orifice provide turbulent voids which break up and clear contaminants from the flow. The system's four-stage compressor features sealed, oil-free compression spaces and a very compact nested piston configuration with a minimum of moving parts and drive complexity. The drive mechanism is a rolling Scotch yoke which minimizes piston side forces and seal wear for prolonged operating life. The closed-cycled system is controlled by an innovative load-responsive electronic feedback circuit which further reduces wear and input power. 6 refs

Statistical sensitivity on right-handed currents in presence of eV scale sterile neutrinos with KATRIN

Science.gov (United States)

Steinbrink, Nicholas M. N.; Glück, Ferenc; Heizmann, Florian; Kleesiek, Marco; Valerius, Kathrin; Weinheimer, Christian; Hannestad, Steen

2017-06-01

The KATRIN experiment aims to determine the absolute neutrino mass by measuring the endpoint region of the tritium β-spectrum. As a large-scale experiment with a sharp energy resolution, high source luminosity and low background it may also be capable of testing certain theories of neutrino interactions beyond the standard model (SM). An example of a non-SM interaction are right-handed currents mediated by right-handed W bosons in the left-right symmetric model (LRSM). In this extension of the SM, an additional SU(2)R symmetry in the high-energy limit is introduced, which naturally includes sterile neutrinos and predicts the seesaw mechanism. In tritium β decay, this leads to an additional term from interference between left- and right-handed interactions, which enhances or suppresses certain regions near the endpoint of the beta spectrum. In this work, the sensitivity of KATRIN to right-handed currents is estimated for the scenario of a light sterile neutrino with a mass of some eV. This analysis has been performed with a Bayesian analysis using Markov Chain Monte Carlo (MCMC). The simulations show that, in principle, KATRIN will be able to set sterile neutrino mass-dependent limits on the interference strength. The sensitivity is significantly increased if the Q value of the β decay can be sufficiently constrained. However, the sensitivity is not high enough to improve current upper limits from right-handed W boson searches at the LHC.

Statistical sensitivity on right-handed currents in presence of eV scale sterile neutrinos with KATRIN

International Nuclear Information System (INIS)

Steinbrink, Nicholas M.N.; Weinheimer, Christian; Glück, Ferenc; Valerius, Kathrin; Heizmann, Florian; Kleesiek, Marco; Hannestad, Steen

2017-01-01

The KATRIN experiment aims to determine the absolute neutrino mass by measuring the endpoint region of the tritium β-spectrum. As a large-scale experiment with a sharp energy resolution, high source luminosity and low background it may also be capable of testing certain theories of neutrino interactions beyond the standard model (SM). An example of a non-SM interaction are right-handed currents mediated by right-handed W bosons in the left-right symmetric model (LRSM). In this extension of the SM, an additional SU(2) R symmetry in the high-energy limit is introduced, which naturally includes sterile neutrinos and predicts the seesaw mechanism. In tritium β decay, this leads to an additional term from interference between left- and right-handed interactions, which enhances or suppresses certain regions near the endpoint of the beta spectrum. In this work, the sensitivity of KATRIN to right-handed currents is estimated for the scenario of a light sterile neutrino with a mass of some eV. This analysis has been performed with a Bayesian analysis using Markov Chain Monte Carlo (MCMC). The simulations show that, in principle, KATRIN will be able to set sterile neutrino mass-dependent limits on the interference strength. The sensitivity is significantly increased if the Q value of the β decay can be sufficiently constrained. However, the sensitivity is not high enough to improve current upper limits from right-handed W boson searches at the LHC.

Statistical sensitivity on right-handed currents in presence of eV scale sterile neutrinos with KATRIN

Energy Technology Data Exchange (ETDEWEB)

Steinbrink, Nicholas M.N.; Weinheimer, Christian [Institute for Nuclear Physics, University of Münster, Wilhelm Klemm-Str. 9, 41849 Münster (Germany); Glück, Ferenc; Valerius, Kathrin [Institute for Nuclear Physics, Karlsruhe Institute of Technology, P.O. Box 3640, 76021 Karlsruhe (Germany); Heizmann, Florian; Kleesiek, Marco [Institute of Experimental Nuclear Physics, Karlsruhe Institute of Technology, P.O. Box 3640, 76021 Karlsruhe (Germany); Hannestad, Steen, E-mail: n.steinbrink@uni-muenster.de, E-mail: ferenc.glueck@kit.edu, E-mail: florian.heizmann@kit.edu, E-mail: marco.kleesiek@kit.edu, E-mail: kathrin.valerius@kit.edu, E-mail: weinheimer@uni-muenster.de, E-mail: steen@phys.au.dk [Department of Physics and Astronomy, Aarhus University, Ny Munkegade 120, 8000 Aarhus C (Denmark)

2017-06-01

The KATRIN experiment aims to determine the absolute neutrino mass by measuring the endpoint region of the tritium β-spectrum. As a large-scale experiment with a sharp energy resolution, high source luminosity and low background it may also be capable of testing certain theories of neutrino interactions beyond the standard model (SM). An example of a non-SM interaction are right-handed currents mediated by right-handed W bosons in the left-right symmetric model (LRSM). In this extension of the SM, an additional SU(2){sub R} symmetry in the high-energy limit is introduced, which naturally includes sterile neutrinos and predicts the seesaw mechanism. In tritium β decay, this leads to an additional term from interference between left- and right-handed interactions, which enhances or suppresses certain regions near the endpoint of the beta spectrum. In this work, the sensitivity of KATRIN to right-handed currents is estimated for the scenario of a light sterile neutrino with a mass of some eV. This analysis has been performed with a Bayesian analysis using Markov Chain Monte Carlo (MCMC). The simulations show that, in principle, KATRIN will be able to set sterile neutrino mass-dependent limits on the interference strength. The sensitivity is significantly increased if the Q value of the β decay can be sufficiently constrained. However, the sensitivity is not high enough to improve current upper limits from right-handed W boson searches at the LHC.

Ruumi kohta arvamuse avaldamiseks ei pea olema arhitekt / Katrin Koov, Ave Kongo ; intervjueerinud Merle Karro-Kalberg

Index Scriptorium Estoniae

Koov, Katrin, 1973-

2016-01-01

Erahuvikoolina tegutseva arhitektuurikooli eestvedamisel töötatakse välja ruumiõppe valikainemoodulit gümnaasiumile. Ruumiõppest räägivad arhitektide liidu president, arhitektuurikooli õpetaja Katrin Koov ja Saue gümnaasiumi kunstiõpetaja Ave Kongo

Mechanism and pharmacological rescue of berberine-induced hERG channel deficiency

Directory of Open Access Journals (Sweden)

Yan M

2015-10-01

Full Text Available Meng Yan,1 Kaiping Zhang,1 Yanhui Shi,1 Lifang Feng,1 Lin Lv,1 Baoxin Li1,2 1Department of Pharmacology, Harbin Medical University, 2State-Province Key Laboratory of Biopharmaceutical Engineering, Harbin, Heilongjiang, People’s Republic of China Abstract: Berberine (BBR, an isoquinoline alkaloid mainly isolated from plants of Berberidaceae family, is extensively used to treat gastrointestinal infections in clinics. It has been reported that BBR can block human ether-a-go-go-related gene (hERG potassium channel and inhibit its membrane expression. The hERG channel plays crucial role in cardiac repolarization and is the target of diverse proarrhythmic drugs. Dysfunction of hERG channel can cause long QT syndrome. However, the regulatory mechanisms of BBR effects on hERG at cell membrane level remain unknown. This study was designed to investigate in detail how BBR decreased hERG expression on cell surface and further explore its pharmacological rescue strategies. In this study, BBR decreases caveolin-1 expression in a concentration-dependent manner in human embryonic kidney 293 (HEK293 cells stably expressing hERG channel. Knocking down the basal expression of caveolin-1 alleviates BBR-induced hERG reduction. In addition, we found that aromatic tyrosine (Tyr652 and phenylalanine (Phe656 in S6 domain mediate the long-term effect of BBR on hERG by using mutation techniques. Considering both our previous and present work, we propose that BBR reduces hERG membrane stability with multiple mechanisms. Furthermore, we found that fexofenadine and resveratrol shorten action potential duration prolongated by BBR, thus having the potential effects of alleviating the cardiotoxicity of BBR. Keywords: berberine, hERG, cavoline-1, cardiotoxicity, LQTS, pharmacological rescue

The transcription factor ERG increases expression of neurotransmitter receptors on prostate cancer cells

International Nuclear Information System (INIS)

Kissick, Haydn T.; On, Seung T.; Dunn, Laura K.; Sanda, Martin G.; Asara, John M.; Pellegrini, Kathryn L.; Noel, Jonathan K.; Arredouani, Mohamed S.

2015-01-01

The TMPRSS2-ERG gene fusion occurs in about half of prostate cancer (PCa) cases and results in overexpression of the transcription factor ERG. Overexpression of ERG has many effects on cellular function. However, how these changes enhance cell growth and promote tumor development is unclear. To investigate the role of ERG, LNCaP and PC3 cells were transfected with ERG and gene expression and metabolic profile were analyzed. Our data show that expression of ERG induces overexpression of many nicotinicacetylcholine receptors (nAChRs). In addition, metabolic profiling by LC-MS/MS revealed elevated production of several neurotransmitters in cells expressing ERG. Consistently, treatment of ERG-expressing cells with nicotine induced elevated calcium influx, GSK3β (Ser9) phosphorylation and cell proliferation. Finally, we show that PCa patientswho are smokers have larger tumors if their tumors are TMPRSS2-ERG gene fusion positive. Collectively, our data suggest that ERG sensitizes prostate tumor cells to neurotransmitter receptor agonists like nicotine. The online version of this article (doi:10.1186/s12885-015-1612-3) contains supplementary material, which is available to authorized users

ERG review of containment failure probability and repository functional design criteria

International Nuclear Information System (INIS)

Gopal, S.

1986-06-01

The Engineering Review Group (ERG) was established by the Office of Nuclear Waste Isolation (ONWI) to help evaluate engineering-related issues in the US Department of Energy's nuclear waste repository program. The June 1984 meeting of the ERG considered two topics: (1) statistical probability for containment of nuclides within the waste package and (2) repository design criteria. This report documents the ERG's comments and recommendations on these two subjects and the ONWI response to the specific points raised by ERG

The source of monoenergetic electrons for the monitoring of spectrometer in the KATRIN neutrino experiment

CERN Document Server

Slezák, Martin

The international project KATRIN (KArlsruhe TRItium Neutrino experiment) is a next-generation tritium $\\beta$-decay experiment. It is designed to measure the electron anti-neutrino mass by means of a unique electron spectrometer with sensitivity of 0.2 eV/c$^2$. This is an improvement of one order of magnitude over the last results. Important part of the measurement will rest in continuous precise monitoring of high voltage of the KATRIN main spectrometer. The monitoring will be done by means of conversion electrons emitted from a solid source based on $^{83}$Rb decay. Properties of several of these sources are studied in this thesis by means of the semiconductor $\\gamma$-ray spectroscopy. Firstly, measurement of precise energy of the 9.4 keV nuclear transition observed in $^{83}$Rb decay, from which the energy of conversion electrons is derived, is reported. Secondly, measurement of activity distribution of the solid sources by means of the Timepix detector is described. Finally, a report on measurement of r...

Voltage-Dependent Gating of hERG Potassium Channels

Science.gov (United States)

Cheng, Yen May; Claydon, Tom W.

2012-01-01

The mechanisms by which voltage-gated channels sense changes in membrane voltage and energetically couple this with opening of the ion conducting pore has been the source of significant interest. In voltage-gated potassium (Kv) channels, much of our knowledge in this area comes from Shaker-type channels, for which voltage-dependent gating is quite rapid. In these channels, activation and deactivation are associated with rapid reconfiguration of the voltage-sensing domain unit that is electromechanically coupled, via the S4–S5 linker helix, to the rate-limiting opening of an intracellular pore gate. However, fast voltage-dependent gating kinetics are not typical of all Kv channels, such as Kv11.1 (human ether-à-go-go related gene, hERG), which activates and deactivates very slowly. Compared to Shaker channels, our understanding of the mechanisms underlying slow hERG gating is much poorer. Here, we present a comparative review of the structure–function relationships underlying activation and deactivation gating in Shaker and hERG channels, with a focus on the roles of the voltage-sensing domain and the S4–S5 linker that couples voltage sensor movements to the pore. Measurements of gating current kinetics and fluorimetric analysis of voltage sensor movement are consistent with models suggesting that the hERG activation pathway contains a voltage independent step, which limits voltage sensor transitions. Constraints upon hERG voltage sensor movement may result from loose packing of the S4 helices and additional intra-voltage sensor counter-charge interactions. More recent data suggest that key amino acid differences in the hERG voltage-sensing unit and S4–S5 linker, relative to fast activating Shaker-type Kv channels, may also contribute to the increased stability of the resting state of the voltage sensor. PMID:22586397

Voltage-dependent gating of hERG potassium channels

Directory of Open Access Journals (Sweden)

Yen May eCheng

2012-05-01

Full Text Available The mechanisms by which voltage-gated channels sense changes in membrane voltage and energetically couple this with opening of the ion conducting pore has been the source of significant interest. In voltage-gated potassium (Kv channels, much of our knowledge in this area comes from Shaker-type channels, for which voltage-dependent gating is quite rapid. In these channels, activation and deactivation are associated with rapid reconfiguration of the voltage-sensing domain unit that is electromechanically coupled, via the S4-S5 linker helix, to the rate-limiting opening of an intracellular pore gate. However, fast voltage-dependent gating kinetics are not typical of all Kv channels, such as Kv11.1 (human ether-a-go-go related gene, hERG, which activates and deactivates very slowly. Compared to Shaker channels, our understanding of the mechanisms underlying slow hERG gating is much poorer. Here, we present a comparative review of the structure-function relationships underlying voltage-dependent gating in Shaker and hERG channels, with a focus on the roles of the voltage sensing domain and the S4-S5 linker that couples voltage sensor movements to the pore. Measurements of gating current kinetics and fluorimetric analysis of voltage sensor movement are consistent with models suggesting that the hERG activation pathway contains a voltage independent step, which limits voltage sensor transitions. Constraints upon hERG voltage sensor movement may result from loose packing of the S4 helices and additional intra-voltage sensor counter charge interactions. More recent data suggest that key amino acid differences in the hERG voltage sensing unit and S4-S5 linker, relative to fast activating Shaker-type Kv channels, may also contribute to the increased stability of the resting state of the voltage sensor.

TAB sümpoosion tõi Kultuurikatlasse üle 300 inimese = TAB symposium attracted more than 300 participants / Katrin Koov

Index Scriptorium Estoniae

Koov, Katrin, 1973-

2011-01-01

8.-11. septembrini 2011 toimunud 1. Tallinna arhitektuuribiennaali sümpoosionist, mille teemaks oli maastikuurbanism (landscape urbanism). Kuraator Katrin Koov. Esinejatest, ettekannetest, maasikuurbanismist

Miks meile vaja maastikuarhitektuuri? = Why do we need landscape architecture? / Reinhard Micheller, Günther Schalk, Katrin Koov

Index Scriptorium Estoniae

Micheller, Reinhard, 1977-

2013-01-01

EKA arhitektuuri ja linnaplaneerimise osakonna III kursuse 2009-2012 aastail erialase projekteerimise ülesande raames on vestlusringis maastikuarhitektuurse osa juhendajad Reinhard Micheller ja Günther Schalk (michellerundschalk, München) ning Katrin Koov (KAVAKAVA, EKA maastikuarhitektuuri õppekava juht)

Design of a pulsed angular selective electron gun for the KATRIN main spectrometer

Energy Technology Data Exchange (ETDEWEB)

Winzen, Daniel; Hannen, Volker; Ortjohann, Hans-Werner; Zacher, Michael; Weinheimer, Christian [Institut fuer Kernphysik, Westfaelische Wilhelms-Universitaet, Muenster (Germany); Collaboration: KATRIN-Collaboration

2012-07-01

The KATRIN (KArlsruhe TRItium Neutrino mass) experiment will study the tritium {beta}-spectrum near the endpoint of 18.6 keV, aiming to measure the mass of the electron antineutrino. Using an electrostatic retarding spectrometer (MAC-E-Filter), the projected sensitivity for m{sub ve} is 200 meV/c{sup 2} at 90% C.L. In order to map out the electric and magnetic fields in the main spectrometer, an angular selective electron gun is currently being developed. The e-gun uses an UV-Laser to produce electrons via the photo-electric effect from a copper substrate which are then accelerated electrostatically. It features a small energy spread of approx. 0.1 eV, a sharp emission angle and will be able to cover the whole magnetic flux tube of KATRIN. Using a pulsed laser it is also possible to investigate the time of flight (TOF) of electrons through the spectrometer, offering enhanced sensitivity to spectrometer properties far away from the analysing plane. By comparing information from transmission function measurements and TOF data with Monte Carlo simulations of the setup, one will be able to achieve a detailed understanding of the spectrometer properties.

Overview of recent and current spectroscopic investigations with hydrogen isotopologues for KATRIN

Energy Technology Data Exchange (ETDEWEB)

Brunst, Tim; Mirz, Sebastian; Groessle, Robin; Krasch, Bennet [Karlsruhe Institute of Technology KIT (Germany). Institute for Technical Physics (ITEP), Tritium Laboratory Karlsruhe (TLK); Collaboration: KATRIN-Collaboration

2016-07-01

The Karlsruhe Tritium Neutrino Experiment (KATRIN) investigates the energy spectrum of the tritium β decay near its energetic endpoint in order to determine the electron anti-neutrino mass with a sensitivity of 200 meV/c{sup 2} (90 % C.L.). Therefore, molecular tritium gas is decaying in a windowless gaseous tritium source (WGTS). The physical properties of the gas in the WGTS, like composition, ortho/para ratio or rotational population, need to be stabilised on a 10{sup -3} level due to their direct impact on the initial state distribution of the investigated β decay. In order to obtain a complete model of the molecular processes in the sample various spectroscopic measurements of mixtures with non-radioactive isotopologues (H{sub 2},HD,D{sub 2}) have been using IR spectroscopy in the liquid at temperatures <25 K and Raman spectroscopy in the gaseous phase at room temperature. This poster presents an overview of recent and current investigations with TApIR: The investigation of dimer and cluster formation under KATRIN conditions, as well as the ongoing task to investigate mixtures beyond the thermal equilibrium with highly concentrated HD and the design of a tritium compatible system for temperatures between (15-293) K.

In vitro chronic effects on hERG channel caused by the marine biotoxin Yessotoxin.

Directory of Open Access Journals (Sweden)

Sara Fernández Ferreiro

2014-06-01

Currently, published evidence indicates that hERG channel dysfunction can be due to more than one mechanism for many drugs (Guth, 2007. Alterations of hERG channel trafficking are considered an important factor in hERG-related cardiotoxicity. Actually, a screening study revealed that almost 40% of the drugs that block Ikr have also trafficking effects (Wible et al., 2005. Although YTX does not block hERG channels, it has been historically described as cardiotoxic due to in vivo damage to cardiomyocytes. Our results show that YTX induces a significant increase of hERG channel levels on the extracellular side of the plasma membrane in vitro. YTX causes cell death in many cell lines (Korsnes and Espenes, 2011 and the alterations of surface hERG levels might be related to the apoptotic process. However, annexin-V, a relatively early marker of apoptosis (Vermes et al., 1995, occurs later than the increase of surface hERG. Additionally, staurosporine triggered apoptosis without a simultaneous increase of surface hERG, so events are not necessarily related. Therefore YTX-induced elevated hERG in the plasma membrane seem to be independent of apoptosis. Functional implications of hERG currents have been described after alterations of cell surface hERG density (Guth, 2007. YTX did not cause significant alterations of hERG currents. Furthermore the hERG levels after YTX treatment were duplicated, so the effect on currents should be clearly evidenced if these channels were functional. The hERG channels on the cell surface are regulated by its production, translocation to the plasma membrane and degradation. The increase of extracellular channel could be a consequence of a higher production and externalization or a slower degradation. Higher synthesis in our cell model would not be physiologically relevant but our results demonstrated that the amount of immature hERG is reduced instead of increased. Fully glycosylated hERG seems slightly increased in these conditions but it is

ERG oncoprotein expression in prostate carcinoma patients of different ethnicities

OpenAIRE

KELLY, GREGORY M.; KONG, YINK HEAY; DOBI, ALBERT; SRIVASTAVA, SHIV; SESTERHENN, ISABELL A.; PATHMANATHAN, RAJADURAI; TAN, HUI MENG; TAN, SHYH-HAN; CHEONG, SOK CHING

2014-01-01

Overexpression of the erythroblast transformation-specific-related gene (ERG) oncoprotein due to transmembrane protease, serine 2 (TMPRSS2)-ERG fusion, the most prevalent genomic alteration in prostate cancer (CaP), is more frequently observed among Caucasian patients compared to patients of African or Asian descent. To the best of our knowledge, this is the first study to investigate the prevalence of ERG alterations in a multiethnic cohort of CaP patients. A total of 191 formalin-fixed para...

Reduction in cryptosporidiosis associated with introduction of enhanced filtration of drinking water at Loch Katrine, Scotland.

Science.gov (United States)

Pollock, K G J; Young, D; Robertson, C; Ahmed, S; Ramsay, C N

2014-01-01

Previous evidence has suggested an association between cryptosporidiosis and consumption of unfiltered drinking water from Loch Katrine in Scotland. Before September 2007, the water was only micro-strained and chlorinated; however, since that time, coagulation and rapid gravity filtration have been installed. In order to determine risk factors associated with cryptosporidiosis, including drinking water, we analysed data on microbiologically confirmed cases of cryptosporidiosis from 2004 to 2010. We identified an association between the incidence of cryptosporidiosis and unfiltered Loch Katrine drinking water supplied to the home (odds ratio 1.86, 95% confidence interval 1.11-3.11, P = 0.019). However, while filtration appears to be associated with initially reduced rates of cryptosporidiosis, evidence suggests it may paradoxically make those consumers more susceptible to other transmission routes in the long-term. These findings support implementation of similar treatment for other unfiltered drinking-water supplies, as a means of reducing cryptosporidiosis associated with drinking water.

Inhibitory effects and mechanism of dihydroberberine on hERG channels expressed in HEK293 cells.

Directory of Open Access Journals (Sweden)

Dahai Yu

Full Text Available The human ether-a-go-go-related gene (hERG potassium channel conducts rapid delayed rectifier potassium currents (IKr and contributes to phase III cardiac action potential repolarization. Drugs inhibit hERG channels by binding to aromatic residues in hERG helixes. Berberine (BBR has multiple actions, and its hydrogenated derivative dihydroberberine (DHB is a potential candidate for developing new drugs. Previous studies have demonstrated that BBR blocks hERG channels and prolongs action potential duration (APD. Our present study aimed to investigate the effects and mechanism of DHB on hERG channels. Protein expression and the hERG current were analyzed using western blotting and patch-clamp, respectively. DHB inhibited the hERG current concentration-dependently after instantaneous perfusion, accelerated channel inactivation by directly binding tyrosine (Tyr652 and phenylalanine (Phe656, and decreased mature (155-kDa and simultaneously increased immature (135-kDa hERG expression, respectively. This suggests disruption of forward trafficking of hERG channels. Besides, DHB remarkably reduced heat shock protein 90 (Hsp90 expression and its interaction with hERG, indicating that DHB disrupted hERG trafficking by impairing channel folding. Meanwhie, DHB enhanced the expression of cleaved activating transcription factor-6 (ATF-6, a biomarker of unfolded protein response (UPR. Expression of calnexin and calreticulin, chaperones activated by ATF-6 to facilitate channel folding, were also increased, which indicating UPR activation. Additionally, the degradation rate of mature 155-kDa hERG increased following DHB exposure. In conclusion, we demonstrated that DHB acutely blocked hERG channels by binding the aromatic Tyr652 and Phe656. DHB may decrease hERG plasma membrane expression through two pathways involving disruption of forward trafficking of immature hERG channels and enhanced degradation of mature hERG channels. Furthermore, forward trafficking was

Status of the KATRIN focal-plane detector

Energy Technology Data Exchange (ETDEWEB)

Seher, Agnes [Karlsruher Institute of Technology (KIT) (Germany). Institut fuer Kernphysik (IKP); Collaboration: KATRIN-Collaboration

2016-07-01

The KArlsruhe TRItium Neutrino (KATRIN) experiment aims to determine the mass of the electron anti-neutrino with a sensitivity of 200 meV/c{sup 2} by measuring the kinematics of tritium β-electrons close to the enpoint of the energy spectrum. The energy analysis of the experiment is performed with a high-resolution electrostatic spectrometer of MAC-E filter type which acts as an integranting high pass filter. Transmitted electrons are counted with a segmented silicon detector system located at the downstream end of the experiment. The detector system consists of two super-conducting solenoids (B{sub max}=6 T), a post-acceleration electrode, a detector wafer with silicon pixel-diodes, readout electronics as well as a calibration and monitoring devices. This talk gives an overview of the detector system and its current status as well as key performance parameters.

[Follow-up on MEWDS by fundus perimetry and multifocal ERG with the SLO].

Science.gov (United States)

Bültmann, S; Martin, M; Rohrschneider, K

2002-09-01

Most conventional techniques for examination such as perimetry or ERG may not be sensitive enough to detect functional alterations due to MEWDS precisely. We report on a follow-up performed by fundus perimetry and the new technique of multifocal ERG using the scanning laser ophthalmoscope. A 24-year-old female patient (VA 0.2/0.8) was followed up for 7 weeks with these techniques as well as Octopus perimetry, fluorescence angiography, Ganzfeld ERG and biomicroscopy. Multifocal ERG stimulation (mfERG, Retiscan) was performed with the SLO. Visual acuity improved from 0.2 to 0.8 and the central relative scotoma disappeared while a relevant increase of P1-wave amplitudes in mfERG could be observed. Combining objective measurements from the fundus controlled SLO-mfERG and results from fundus perimetry enable good correlation of morphology and results, even for minor alterations of the macula only accessible by few established clinical examinations.

Antineoplastic Effects of siRNA against TMPRSS2-ERG Junction Oncogene in Prostate Cancer.

Directory of Open Access Journals (Sweden)

Giorgia Urbinati

Full Text Available TMPRSS2-ERG junction oncogene is present in more than 50% of patients with prostate cancer and its expression is frequently associated with poor prognosis. Our aim is to achieve gene knockdown by siRNA TMPRSS2-ERG and then to assess the biological consequences of this inhibition. First, we designed siRNAs against the two TMPRSS2-ERG fusion variants (III and IV, most frequently identified in patients' biopsies. Two of the five siRNAs tested were found to efficiently inhibit mRNA of both TMPRSS2-ERG variants and to decrease ERG protein expression. Microarray analysis further confirmed ERG inhibition by both siRNAs TMPRSS2-ERG and revealed one common down-regulated gene, ADRA2A, involved in cell proliferation and migration. The siRNA against TMPRSS2-ERG fusion variant IV showed the highest anti-proliferative effects: Significantly decreased cell viability, increased cleaved caspase-3 and inhibited a cluster of anti-apoptotic proteins. To propose a concrete therapeutic approach, siRNA TMPRSS2-ERG IV was conjugated to squalene, which can self-organize as nanoparticles in water. The nanoparticles of siRNA TMPRSS2-ERG-squalene injected intravenously in SCID mice reduced growth of VCaP xenografted tumours, inhibited oncoprotein expression and partially restored differentiation (decrease in Ki67. In conclusion, this study offers a new prospect of treatment for prostate cancer based on siRNA-squalene nanoparticles targeting TMPRSS2-ERG junction oncogene.

Development of Peptidomimetic Inhibitors of the ERG Gene Fusion Product in Prostate Cancer.

Science.gov (United States)

Wang, Xiaoju; Qiao, Yuanyuan; Asangani, Irfan A; Ateeq, Bushra; Poliakov, Anton; Cieślik, Marcin; Pitchiaya, Sethuramasundaram; Chakravarthi, Balabhadrapatruni V S K; Cao, Xuhong; Jing, Xiaojun; Wang, Cynthia X; Apel, Ingrid J; Wang, Rui; Tien, Jean Ching-Yi; Juckette, Kristin M; Yan, Wei; Jiang, Hui; Wang, Shaomeng; Varambally, Sooryanarayana; Chinnaiyan, Arul M

2017-04-10

Transcription factors play a key role in the development of diverse cancers, and therapeutically targeting them has remained a challenge. In prostate cancer, the gene encoding the transcription factor ERG is recurrently rearranged and plays a critical role in prostate oncogenesis. Here, we identified a series of peptides that interact specifically with the DNA binding domain of ERG. ERG inhibitory peptides (EIPs) and derived peptidomimetics bound ERG with high affinity and specificity, leading to proteolytic degradation of the ERG protein. The EIPs attenuated ERG-mediated transcription, chromatin recruitment, protein-protein interactions, cell invasion and proliferation, and tumor growth. Thus, peptidomimetic targeting of transcription factor fusion products may provide a promising therapeutic strategy for prostate cancer as well as other malignancies. Copyright © 2017 Elsevier Inc. All rights reserved.

ERG and other discriminators between advanced hydroxychloroquine retinopathy and retinitis pigmentosa.

Science.gov (United States)

Nair, Archana A; Marmor, Michael F

2017-06-01

To study whether the ERG and other clinical findings help to distinguish between advanced hydroxychloroquine (HCQ) retinopathy and pericentral or diffuse retinitis pigmentosa (RP) with similar fundus appearance. We conducted a retrospective analysis of patients with advanced HCQ retinopathy (n = 11), pericentral RP (n = 8) and diffuse RP (n = 8). Pericentral RP was defined as having limited fundus damage and relatively normal flicker ERG time-to-peak. Diffuse RP had typical loss of the rod ERG and flicker timing delay. All patients showed reduced amplitude of the ISCEV responses in the full-field electroretinogram (ERG). Aspects of history, visual field results, fundus appearance, fundus autofluorescence and ocular coherence tomography were also compared. Relative to pericentral RP, patients with HCQ toxicity showed delayed flicker ERG time-to-peak and lower ERG amplitudes, particularly combined rod-cone responses. Relative to diffuse RP, most HCQ toxicity patients had some preserved rod ERG response, and there was no obvious predilection for rod over cone damage. In addition, patients with HCQ toxicity usually lacked markers of long-standing degeneration such as bone spicule figures or severe loss of peripheral field. History of familial disease and long-standing night blindness were specific to RP. While the early signs of HCQ damage are typically regional in the posterior pole, advanced disease is characteristically diffuse (unlike pericentral RP). This is appropriate for a systemic toxin, as is the finding that rods and cones were both affected in the ERG to a similar degree (unlike genetic rod-cone dystrophies). For patients with severe HCQ exposure and some of our discriminatory findings, and no family history or prior night blindness, HCQ toxicity is a sufficient diagnosis without invoking a second rare disease (Occam's razor).

Channel sialic acids limit hERG channel activity during the ventricular action potential.

Science.gov (United States)

Norring, Sarah A; Ednie, Andrew R; Schwetz, Tara A; Du, Dongping; Yang, Hui; Bennett, Eric S

2013-02-01

Activity of human ether-a-go-go-related gene (hERG) 1 voltage-gated K(+) channels is responsible for portions of phase 2 and phase 3 repolarization of the human ventricular action potential. Here, we questioned whether and how physiologically and pathophysiologically relevant changes in surface N-glycosylation modified hERG channel function. Voltage-dependent hERG channel gating and activity were evaluated as expressed in a set of Chinese hamster ovary (CHO) cell lines under conditions of full glycosylation, no sialylation, no complex N-glycans, and following enzymatic deglycosylation of surface N-glycans. For each condition of reduced glycosylation, hERG channel steady-state activation and inactivation relationships were shifted linearly by significant depolarizing ∼9 and ∼18 mV, respectively. The hERG window current increased significantly by 50-150%, and the peak shifted by a depolarizing ∼10 mV. There was no significant change in maximum hERG current density. Deglycosylated channels were significantly more active (20-80%) than glycosylated controls during phases 2 and 3 of action potential clamp protocols. Simulations of hERG current and ventricular action potentials corroborated experimental data and predicted reduced sialylation leads to a 50-70-ms decrease in action potential duration. The data describe a novel mechanism by which hERG channel gating is modulated through physiologically and pathophysiologically relevant changes in N-glycosylation; reduced channel sialylation increases hERG channel activity during the action potential, thereby increasing the rate of action potential repolarization.

Multifocal ERG wavelet packet decomposition applied to glaucoma diagnosis

Directory of Open Access Journals (Sweden)

Rodríguez-Ascariz José M

2011-05-01

Full Text Available Abstract Background Glaucoma is the second-leading cause of blindness worldwide and early diagnosis is essential to its treatment. Current clinical methods based on multifocal electroretinography (mfERG essentially involve measurement of amplitudes and latencies and assume standard signal morphology. This paper presents a new method based on wavelet packet analysis of global-flash multifocal electroretinogram signals. Methods This study comprised twenty-five patients diagnosed with OAG and twenty-five control subjects. Their mfERG recordings data were used to develop the algorithm method based on wavelet packet analysis. By reconstructing the third wavelet packet contained in the fourth decomposition level (ADAA4 of the mfERG recording, it is possible to obtain a signal from which to extract a marker in the 60-80 ms time interval. Results The marker found comprises oscillatory potentials with a negative-slope basal line in the case of glaucomatous recordings and a positive-slope basal line in the case of normal signals. Application of the optimal threshold calculated in the validation cases showed that the technique proposed achieved a sensitivity of 0.81 and validation specificity of 0.73. Conclusions This new method based on mfERG analysis may be reliable enough to detect functional deficits that are not apparent using current automated perimetry tests. As new stimulation and analysis protocols develop, mfERG has the potential to become a useful tool in early detection of glaucoma-related functional deficits.

Kuhu lähed, Kultuurikatel? / Thuur Caris, Renger Koning, Arne Lösekann ; interv. Katrin Koov, Regina Viljasaar

Index Scriptorium Estoniae

Caris, Thuur

2008-01-01

Endise Tallinna soojuselektrijaama kompleksis asuva Kultuurikatla ruumide võimalusi uuriv workshop, korraldajaks MTÜ Kultuurikatel koos Kavakava arhitektide Siiri Vallneri ja Katrin Kooviga. Hollandi meediakunstnik Thuur Caris ja helilooja ning helidisainer Renger Koning tutvustavad Groningeni Pudingivabrikut. Saksa arhitekt ja kunstnik Arne Lösekann tutvustab Kubasta kunstikeskust Hamburgis

Dynamic regulation of canonical TGFβ signalling by endothelial transcription factor ERG protects from liver fibrogenesis.

Science.gov (United States)

Dufton, Neil P; Peghaire, Claire R; Osuna-Almagro, Lourdes; Raimondi, Claudio; Kalna, Viktoria; Chuahan, Abhishek; Webb, Gwilym; Yang, Youwen; Birdsey, Graeme M; Lalor, Patricia; Mason, Justin C; Adams, David H; Randi, Anna M

2017-10-12

The role of the endothelium in protecting from chronic liver disease and TGFβ-mediated fibrosis remains unclear. Here we describe how the endothelial transcription factor ETS-related gene (ERG) promotes liver homoeostasis by controlling canonical TGFβ-SMAD signalling, driving the SMAD1 pathway while repressing SMAD3 activity. Molecular analysis shows that ERG binds to SMAD3, restricting its access to DNA. Ablation of ERG expression results in endothelial-to-mesenchymal transition (EndMT) and spontaneous liver fibrogenesis in EC-specific constitutive hemi-deficient (Erg cEC-Het ) and inducible homozygous deficient mice (Erg iEC-KO ), in a SMAD3-dependent manner. Acute administration of the TNF-α inhibitor etanercept inhibits carbon tetrachloride (CCL 4 )-induced fibrogenesis in an ERG-dependent manner in mice. Decreased ERG expression also correlates with EndMT in tissues from patients with end-stage liver fibrosis. These studies identify a pathogenic mechanism where loss of ERG causes endothelial-dependent liver fibrogenesis via regulation of SMAD2/3. Moreover, ERG represents a promising candidate biomarker for assessing EndMT in liver disease.The transcription factor ERG is key to endothelial lineage specification and vascular homeostasis. Here the authors show that ERG balances TGFβ signalling through the SMAD1 and SMAD3 pathways, protecting the endothelium from endothelial-to-mesenchymal transition and consequent liver fibrosis in mice via a SMAD3-dependent mechanism.

Final Techno-Economic Analysis of 550 MWe Supercritical PC Power Plant CO₂ Capture with Linde-BASF Advanced PCC Technology

Energy Technology Data Exchange (ETDEWEB)

Bostick, Devin [Linde LLC, Murray Hill, NJ (United States); Stoffregen, Torsten [Linde AG Linde Engineering Division, Dresden (Germany); Rigby, Sean [BASF Corporation, Houston, TX (United States)

2017-01-09

This topical report presents the techno-economic evaluation of a 550 MWe supercritical pulverized coal (PC) power plant utilizing Illinois No. 6 coal as fuel, integrated with 1) a previously presented (for a subcritical PC plant) Linde-BASF post-combustion CO₂ capture (PCC) plant incorporating BASF’s OASE® blue aqueous amine-based solvent (LB1) [Ref. 6] and 2) a new Linde-BASF PCC plant incorporating the same BASF OASE® blue solvent that features an advanced stripper interstage heater design (SIH) to optimize heat recovery in the PCC process. The process simulation and modeling for this report is performed using Aspen Plus V8.8. Technical information from the PCC plant is determined using BASF’s proprietary thermodynamic and process simulation models. The simulations developed and resulting cost estimates are first validated by reproducing the results of DOE/NETL Case 12 representing a 550 MWe supercritical PC-fired power plant with PCC incorporating a monoethanolamine (MEA) solvent as used in the DOE/NETL Case 12 reference [Ref. 2]. The results of the techno-economic assessment are shown comparing two specific options utilizing the BASF OASE® blue solvent technology (LB1 and SIH) to the DOE/NETL Case 12 reference. The results are shown comparing the energy demand for PCC, the incremental fuel requirement, and the net higher heating value (HHV) efficiency of the PC power plant integrated with the PCC plant. A comparison of the capital costs for each PCC plant configuration corresponding to a net 550 MWe power generation is also presented. Lastly, a cost of electricity (COE) and cost of CO₂ captured assessment is shown illustrating the substantial cost reductions achieved with the Linde-BASF PCC plant utilizing the advanced SIH configuration in combination with BASF’s OASE® blue solvent technology as compared to the DOE/NETL Case 12 reference. The key factors contributing to the reduction of COE and the cost of CO₂ captured

The Influence of Brightness on Functional Assessment by mfERG

DEFF Research Database (Denmark)

Christiansen, A T; Kiilgaard, J F; Smith, M

2012-01-01

To determine the effect of membrane brightness on multifocal electroretinograms (mfERGs), we implanted poly lactic-co-glycolic acid (PLGA) membranes in the subretinal space of 11 porcine eyes. We compared membranes with their native shiny white color with membranes that were stained with a blue dye...... (Brilliant Blue). Histological and electrophysiological evaluation of the overlying retina was carried out 6 weeks after implantation. Histologically, both white and blue membranes degraded in a spongiform manner leaving a disrupted outer retina with no preserved photoreceptor segments. Multifocal ERG...... when the adjacent photoreceptors are missing. Functional assessment with mfERG in scaffold implant studies should therefore be evaluated with care....

Mida teie oma tervise heaks teete? / Ly Jagor, Ülle Mihhailova, Ene Pill, Katrin Käbin...[jt.

Index Scriptorium Estoniae

2008-01-01

Küsimusele vastavad Pärnu Õppenõustamiskeskuse psühholoog Ly Jagor, Maasika lasteaia juhataja asetäitja Ülle Mihhailova, Tallinna Perekeskuse ja Tähetorni lastekeskuse psühholoog Ene Pill, Tallinna Nõmme Noortemaja väikelaste ringijuht Katrin Käbin, Tääksi Põhikooli õpetaja Silva Kolk

A comparison of two patient friendly ERG electrodes

International Nuclear Information System (INIS)

Hidajat, R.; McLay, J.; Elder, M.; Burley, C.; Goode, D.; Morton, J.

2000-01-01

Full text: The ideal electroretinography (ERG) electrode should provide reproducible waveforms, maximal amplitudes and minimal irritation of the patient's eyes. Contact lens electrodes (e.g. Burian-Allen, ERG jet) generate large amplitudes but are very uncomfortable and quite intimidating for the patient. Two other types, the gold foil and the H-K loop, provide a much more patient friendly alternative at the cost of somewhat reduced amplitudes. With the purchase of a new Nicolet Bravo electrodiagnostic system we had to select a suitable type of ERG electrode and establish the normal range for each ERG test with that electrode. It was decided to trial two electrodes, the gold foil (CH Electronics, UK) and the H-K loop (Avanta, Slovenia) before making the final choice. Seventeen normal volunteers, ranging in age from 14 to 56 years, were subjected to three standard measurements namely the flash photopic, white flash scotopic and transient pattern (PERG) ERG. Each test followed the guidelines set by the International Society for Clinical Electrophysiology of Vision (ISCEV). Before starting the measurements both eyes were anaesthetised with Ophthetic and for the flash ERG's the pupils were dilated with 1% Tropicamide. Immediately after the measurements each subject was asked which electrode was most comfortable. As specified by ISCEV the amplitudes were measured between adjacent troughs and peaks. The mean and standard deviation of the flash ERG b wave and the PERG P 50 amplitudes for each electrode are shown m the accompanying table together with the mean and standard deviation of the ratios of the amplitudes (gold foil/H-K loop) from each subject. It can be seen that the amplitudes measured with the gold foil electrodes are approximately twice those from the H-K loop and that the fractional variation (standard deviation/mean) of the gold foil amplitudes is also lower. In addition nearly all the subjects (13/17) felt less discomfort with the gold foil electrodes, only

Requirements on read-out electronics for future keV-scale sterile neutrino search with KATRIN

Energy Technology Data Exchange (ETDEWEB)

Dolde, Kai [Karlsruhe Institute of Technology (KIT), Karlsruhe (Germany)

2016-07-01

Recent publications show the great potential of the KATRIN (KArlsruhe TRItium Neutrino) experiment in the search for sterile neutrinos in the mass range of a few keV down to active-to-sterile mixing angles at least one order of magnitude smaller than current laboratory limits of sin{sup 2}θ < 10{sup -3}. In order to be sensitive to the tiny kink-like signature of sterile neutrinos in tritium beta decay, KATRIN requires a novel sophisticated detector and read-out system. Several silicon prototype detectors are under construction at the moment to explore the most suitable detector design for this purpose. The selection of appropriate read-out electronics is strongly triggered by the requirements of allowing only very small systematic uncertainties due to ADC Non-Linearities to reach the expected sensitivity. This talk investigates the impact of ADC Non-Linearities on the tritium beta decay spectrum, depending on the digitization method of analogue signals of a multi-pixel silicon detector, peak sensing or waveform digitization. The simulations show a higher achievable sensitivity using waveform digitizers and moreover strongly favor additional variable post-acceleration of the electrons to smear out the periodic structure of the ADC Non-Linearities.

Removal of stored particle background via the electric dipole method in the KATRIN main spectrometer

Energy Technology Data Exchange (ETDEWEB)

Hilk, Daniel [Institut fuer Experimentelle Kernphysik, KIT, Karlsruhe (Germany); Collaboration: KATRIN-Collaboration

2016-07-01

The goal of the KArlsruhe TRItium Neutrino (KATRIN) experiment is to determine the effective mass of the electron anti neutrino by measuring the electron energy spectrum of tritium beta decay near the endpoint. The goal is to reach a sensitivity on the neutrino mass of 200 meV for which a low background level of 10{sup -2} counts per second is mandatory. Electrons from single radioactive decays of radon and tritium in the KATRIN main spectrometer with energies in the keV range can be magnetically stored for hours. While cooling down via ionization of residual gas molecules, they produce hundreds of secondary electrons, which can reach the detector and contribute to the background signals. In order to suppress this background component, several methods are investigated to remove stored electrons, such as the application of an electric dipole field and the application of magnetic pulses. This talk introduces the mechanism of background production due to stored electrons and their removal by the electric dipole method in the main spectrometer. In context of the spectrometer- and detector-commissioning phase in summer 2015, measurement results of the application of the electric dipole method are presented.

Theory, modeling, and integrated studies in the Arase (ERG) project

Science.gov (United States)

Seki, Kanako; Miyoshi, Yoshizumi; Ebihara, Yusuke; Katoh, Yuto; Amano, Takanobu; Saito, Shinji; Shoji, Masafumi; Nakamizo, Aoi; Keika, Kunihiro; Hori, Tomoaki; Nakano, Shin'ya; Watanabe, Shigeto; Kamiya, Kei; Takahashi, Naoko; Omura, Yoshiharu; Nose, Masahito; Fok, Mei-Ching; Tanaka, Takashi; Ieda, Akimasa; Yoshikawa, Akimasa

2018-02-01

Understanding of underlying mechanisms of drastic variations of the near-Earth space (geospace) is one of the current focuses of the magnetospheric physics. The science target of the geospace research project Exploration of energization and Radiation in Geospace (ERG) is to understand the geospace variations with a focus on the relativistic electron acceleration and loss processes. In order to achieve the goal, the ERG project consists of the three parts: the Arase (ERG) satellite, ground-based observations, and theory/modeling/integrated studies. The role of theory/modeling/integrated studies part is to promote relevant theoretical and simulation studies as well as integrated data analysis to combine different kinds of observations and modeling. Here we provide technical reports on simulation and empirical models related to the ERG project together with their roles in the integrated studies of dynamic geospace variations. The simulation and empirical models covered include the radial diffusion model of the radiation belt electrons, GEMSIS-RB and RBW models, CIMI model with global MHD simulation REPPU, GEMSIS-RC model, plasmasphere thermosphere model, self-consistent wave-particle interaction simulations (electron hybrid code and ion hybrid code), the ionospheric electric potential (GEMSIS-POT) model, and SuperDARN electric field models with data assimilation. ERG (Arase) science center tools to support integrated studies with various kinds of data are also briefly introduced.[Figure not available: see fulltext.

YK-4-279 inhibits ERG and ETV1 mediated prostate cancer cell invasion.

Directory of Open Access Journals (Sweden)

Said Rahim

2011-04-01

Full Text Available Genomic rearrangements involving the ETS family of transcription factors occur in 40-70% of prostate cancer cases. ERG and ETV1 are the most common ETS members observed in these genetic alterations. The high prevalence of these rearrangements and their biological significance represents a novel therapeutic target for the treatment of prostate cancer.We recently reported the development of YK-4-279, a small molecule inhibitor of EWS-FLI1 oncoprotein in Ewing's Sarcoma. Since ERG and ETV1 belong to the same class of ETS factors as FLI1, we tested the ability of YK-4-279 to inhibit biological functions of ERG and ETV1 proteins in prostate cancer. YK-4-279 inhibited ERG and ETV1 mediated transcriptional activity in a luciferase assay. YK-4-279 also decreased ERG and ETV1 downstream target mRNA and protein expression in ETV1-fusion positive LNCaP and ERG fusion positive VCaP cells. YK-4-279 reduced the motility of LNCaP cells in a scratch assay and the invasive phenotype of both LNCaP and VCaP cells in a HUVEC invasion assay. Fusion-negative PC3 cells were unresponsive to YK-4-279. SiRNA mediated ERG knockdown in VCaP cells resulted in a loss of drug responsiveness. Concurrently, transient ERG expression in PC-3 cells resulted in increased invasive potential, which was reduced by YK-4-279.These data demonstrate that YK-4-279 inhibits ERG and ETV1 biological activity in fusion-positive prostate cancer cells leading to decreased motility and invasion. Therefore, YK-4-279 may have an impact on metastasis in prostate cancer and it may be further evaluated for its clinical applications in prostate cancer in addition to Ewing's sarcoma.

Radiochemical and thermal studies of the copper(II)-exchanged form of synthetic zeolite linde sieve A

International Nuclear Information System (INIS)

Banerjee, S.P.

1978-01-01

Synthetic zeolite Linde Sieve A displays a double ion-sieve action. Only small cations can penetrate the single 6-rings into the beta cages. The radiochemical and thermal studies of copper(II)-exchanges form of 4A shows evidence of hydrated copper(II) ions in the zeolite structure. (author)

Ettevõtte edu sisse osta ei saa / Katrin Bats, Janne Laik, Silver Vohu, Evelin Ojamets ; intervjueerinud Küllike Heide

Index Scriptorium Estoniae

2012-01-01

Kommunikatsiooni- ja turundustegevuse korraldusest ettevõtetes, mille suur osa antud projektidest hõlmab kõiki Balti riike. Mõtteid jagavad Katrin Bats Rimi Eesti Food AS-ist, Janne Laik NP Foods Eesti OÜ-st, Silver Vohu SEB Pangast ja Evelin Ojamets Coca-Cola-st

Rab11-dependent Recycling of the Human Ether-a-go-go-related Gene (hERG) Channel*

Science.gov (United States)

Chen, Jeffery; Guo, Jun; Yang, Tonghua; Li, Wentao; Lamothe, Shawn M.; Kang, Yudi; Szendrey, John A.; Zhang, Shetuan

2015-01-01

The human ether-a-go-go-related gene (hERG) encodes the pore-forming subunit of the rapidly activating delayed rectifier potassium channel (IKr). A reduction in the hERG current causes long QT syndrome, which predisposes affected individuals to ventricular arrhythmias and sudden death. We reported previously that hERG channels in the plasma membrane undergo vigorous internalization under low K+ conditions. In the present study, we addressed whether hERG internalization occurs under normal K+ conditions and whether/how internalized channels are recycled back to the plasma membrane. Using patch clamp, Western blot, and confocal imaging analyses, we demonstrated that internalized hERG channels can effectively recycle back to the plasma membrane. Low K+-enhanced hERG internalization is accompanied by an increased rate of hERG recovery in the plasma membrane upon reculture following proteinase K-mediated clearance of cell-surface proteins. The increased recovery rate is not due to enhanced protein synthesis, as hERG mRNA expression was not altered by low K+ exposure, and the increased recovery was observed in the presence of the protein biosynthesis inhibitor cycloheximide. GTPase Rab11, but not Rab4, is involved in the recycling of hERG channels. Interfering with Rab11 function not only delayed hERG recovery in cells after exposure to low K+ medium but also decreased hERG expression and function in cells under normal culture conditions. We concluded that the recycling pathway plays an important role in the homeostasis of plasma membrane-bound hERG channels. PMID:26152716

Aeg ei küsi, kelle hinges laulab lind / Katrin Nielsen

Index Scriptorium Estoniae

Nielsen, Katrin

2000-01-01

Pärnu Mudaravilas avatud nongratalase Asta Isaku maalinäitusest "Looduses ja lootuses" ning Chaplini kunstikeskuses avatud Tammiste hooldekodu elaniku Aivar Kurvitsa maalinäitusest "Ära reosta loodust"

TMPRSS2-ERG gene fusion status in minute (minimal) prostatic adenocarcinoma.

Science.gov (United States)

Albadine, Roula; Latour, Mathieu; Toubaji, Antoun; Haffner, Michael; Isaacs, William B; A Platz, Elizabeth; Meeker, Alan K; Demarzo, Angelo M; Epstein, Jonathan I; Netto, George J

2009-11-01

Minute prostatic adenocarcinomas are considered to be of insufficient virulence. Given recent suggestions of TMPRSS2-ERG gene fusion association with aggressive prostatic adenocarcinoma, we evaluated the incidence of TMPRSS2-ERG fusion in minute prostatic adenocarcinomas. A total of 45 consecutive prostatectomies with minute adenocarcinoma were used for tissue microarray construction. A total of 63 consecutive non-minimal, Gleason Score 6 tumors, from a separate PSA Era prostatectomy tissue microarray, were used for comparison. FISH was carried out using ERG break-apart probes. Tumors were assessed for fusion by deletion (Edel) or split (Esplit), duplicated fusions and low-level copy number gain in normal ERG gene locus. Minute adenocarcinomas: Fusion was evaluable in 32/45 tumors (71%). Fifteen out of 32 (47%) tumors were positive for fusion. Six (19%) were of the Edel class and 7 (22%) were classified as combined Edel+Esplit. Non-minute adenocarcinomas (pT2): Fusion was identified in 20/30 tumors (67%). Four (13%) were of Edel class and 5 (17%) were combined Edel+Esplit. Duplicated fusions were encountered in 5 (16%) tumors. Non-minute adenocarcinomas (pT3): Fusion was identified in 19/33 (58%). Fusion was due to a deletion in 6 (18%) tumors. Seven tumors (21%) were classified as combined Edel+Esplit. One tumor showed Esplit alone. Duplicated fusions were encountered in 3 (9%) cases. The incidence of duplicated fusions was higher in non-minute adenocarcinomas (13 vs 0%; P=0.03). A trend for higher incidence of low-level copy number gain in normal ERG gene locus without fusion was noted in non-minute adenocarcinomas (10 vs 0%; P=0.07). We found a TMPRSS2-ERG fusion rate of 47% in minute adenocarcinomas. The latter is not significantly different from that of grade matched non-minute adenocarcinomas. The incidence of duplicated fusion was higher in non-minute adenocarcinomas. Our finding of comparable rate of TMPRSS2-ERG fusion in minute adenocarcinomas may argue

Molecular mechanisms underlying the pilsicainide-induced stabilization of hERG proteins in transfected mammalian cells

Directory of Open Access Journals (Sweden)

Takeshi Onohara, MD

2017-06-01

Conclusions: Pilsicainide penetrates the plasma membrane, stabilizes WT-hERG proteins by acting as a chemical chaperone, and enhances WT-hERG channel currents. This mechanism could also be applicable to modulations of certain mutant-hERG proteins.

Novel laser ellipsometry method for the KATRIN condensed {sup 83m}Kr source

Energy Technology Data Exchange (ETDEWEB)

Zboril, Miroslav [Muenster Univ. (Germany). Inst. fuer Kernphysik; Collaboration: KATRIN-Collaboration

2013-07-01

One of the systematic effects in the neutrino mass experiment KATRIN are the fluctuations of the electric retarding potential which is experienced by the tritium β electrons on their path through the spectrometer. For the purpose of long-term monitoring of the energy scale stability several calibration electron sources will be utilised at KATRIN. One of them is the condensed {sup 83m}Kr source based on a frozen {sup 83m}Kr film on a HOPG backing at about 20 K. The isomeric state decays via a cascade of highly converted transitions, yielding conversion electron lines with energies ranging from 7.5 keV to 32.1 keV, useful for the energy calibration. The cleanliness of the HOPG backing is crucial as any adsorption of residual gas would shift the kinetic energy of the conversion electrons. The backing is cleaned via laser ablation and resistive heating. The cleanliness is checked via a novel method of laser ellipsometry where the polarisation analysis takes place directly in ultrahigh vacuum. The polarisation analysis is realised by an analyser and light detector at 90 K embedded in the cold baffle. This method allows to determine film thicknesses with a resolution of better than an atomic monolayer. As a byproduct it can be also used to determine the indices of refraction of condensed krypton and of the HOPG backing. The main features of the calibration source will be reviewed and the results of test measurements will be presented.

Functional recovery after experimental RPE debridement, mfERG studies in a porcine model

DEFF Research Database (Denmark)

Sørensen, Nina Buus; Lassota, Nathan; Kyhn, Maria Voss

2013-01-01

BACKGROUND: The correlation between histologically identified regeneration of retinal pigment epithelium (RPE) and functional outcome measured by multifocal electroretinography (mfERG) following surgical debridement is examined in a porcine model. In humans, visual acuity is reduced in diseases......, and by brushing the Bruch's membrane with a silicone catheter. Immediately following surgery (baseline) and after 2 and 6 weeks respectively, the animals were examined by mfERG, fundus photographs (FPs), fluorescein angiograms (FAs), and histopathology. RESULTS: The mfERG P1 amplitude was decreased 2 weeks (T2....... CONCLUSION: This is the first study to show that the histological regeneration of hypopigmented RPE correlates to a return of the retinal function, measured by mfERG....

Application of electroretinography (ERG) in early drug development for assessing retinal toxicity in rats

Energy Technology Data Exchange (ETDEWEB)

Huang, Wenhu, E-mail: wenhu.huang@pfizer.com; Collette, Walter; Twamley, Michelle; Aguirre, Shirley A.; Sacaan, Aida

2015-12-15

Retinal ocular toxicity is among the leading causes of drug development attrition in the pharmaceutical industry. Electroretinography (ERG) is a non-invasive functional assay used to assess neuro-retinal physiological integrity by measuring the electrical responses. To directly assess the utility of ERG, a series of studies was conducted following intravitreal and/or iv administration of pan-cyclin-dependent kinase inhibitors: AG-012,986 and AG-024,322 in rats. Both compounds have previously shown to induce retinal toxicity. Retinal injury was evaluated by ERG, histopathology and TUNEL staining. Intravitreal injection of AG-012,986 at ≥ 10 μg/eye resulted in decreases (60%) in ERG b-wave and microscopic changes of mild to moderate retinal degeneration, and at 30 μg/eye led to additional ophthalmic findings. Intravenous administration of AG-012,986 daily at ≥ 5 mg/kg resulted in dose-related decreases (25 to 40%) in b-wave and sporadic to intense positive TUNEL staining. Intravitreal injection of AG-024,322 at 30 μg/eye also resulted in decreases (50 to 60%) in b-wave, mild to marked retinal degeneration and mild vitreous debris. These experiments demonstrate that ERG can be used as a sensitive and reliable functional tool to evaluate retinal toxicity induced by test compounds in rats complementing other classical ocular safety measurements. - Highlights: • There were strong correlations of ERG readouts to in vivo ophthalmic exams, TUNEL assay, and histopathology. • ERG appears to be more sensitive and can detect retinal functional changes at a very early stage of pathogenesis. • ERG can be incorporated into routine exploratory toxicity study to identify compound ocular safety issues. • In drug discovery, ERG is a quick, non-invasive, sensitive and reliable tool in retinal toxicity de-risking.

Application of electroretinography (ERG) in early drug development for assessing retinal toxicity in rats

International Nuclear Information System (INIS)

Huang, Wenhu; Collette, Walter; Twamley, Michelle; Aguirre, Shirley A.; Sacaan, Aida

2015-01-01

Retinal ocular toxicity is among the leading causes of drug development attrition in the pharmaceutical industry. Electroretinography (ERG) is a non-invasive functional assay used to assess neuro-retinal physiological integrity by measuring the electrical responses. To directly assess the utility of ERG, a series of studies was conducted following intravitreal and/or iv administration of pan-cyclin-dependent kinase inhibitors: AG-012,986 and AG-024,322 in rats. Both compounds have previously shown to induce retinal toxicity. Retinal injury was evaluated by ERG, histopathology and TUNEL staining. Intravitreal injection of AG-012,986 at ≥ 10 μg/eye resulted in decreases (60%) in ERG b-wave and microscopic changes of mild to moderate retinal degeneration, and at 30 μg/eye led to additional ophthalmic findings. Intravenous administration of AG-012,986 daily at ≥ 5 mg/kg resulted in dose-related decreases (25 to 40%) in b-wave and sporadic to intense positive TUNEL staining. Intravitreal injection of AG-024,322 at 30 μg/eye also resulted in decreases (50 to 60%) in b-wave, mild to marked retinal degeneration and mild vitreous debris. These experiments demonstrate that ERG can be used as a sensitive and reliable functional tool to evaluate retinal toxicity induced by test compounds in rats complementing other classical ocular safety measurements. - Highlights: • There were strong correlations of ERG readouts to in vivo ophthalmic exams, TUNEL assay, and histopathology. • ERG appears to be more sensitive and can detect retinal functional changes at a very early stage of pathogenesis. • ERG can be incorporated into routine exploratory toxicity study to identify compound ocular safety issues. • In drug discovery, ERG is a quick, non-invasive, sensitive and reliable tool in retinal toxicity de-risking.

Endocytosis of hERG Is Clathrin-Independent and Involves Arf6

Science.gov (United States)

Abuarab, Nada; Smith, Andrew J.; Hardy, Matthew E. L.; Elliott, David J. S.; Sivaprasadarao, Asipu

2013-01-01

The hERG potassium channel is critical for repolarisation of the cardiac action potential. Reduced expression of hERG at the plasma membrane, whether caused by hereditary mutations or drugs, results in long QT syndrome and increases the risk of ventricular arrhythmias. Thus, it is of fundamental importance to understand how the density of this channel at the plasma membrane is regulated. We used antibodies to an extracellular native or engineered epitope, in conjunction with immunofluorescence and ELISA, to investigate the mechanism of hERG endocytosis in recombinant cells and validated the findings in rat neonatal cardiac myocytes. The data reveal that this channel undergoes rapid internalisation, which is inhibited by neither dynasore, an inhibitor of dynamin, nor a dominant negative construct of Rab5a, into endosomes that are largely devoid of the transferrin receptor. These results support a clathrin-independent mechanism of endocytosis and exclude involvement of dynamin-dependent caveolin and RhoA mechanisms. In agreement, internalised hERG displayed marked overlap with glycosylphosphatidylinositol-anchored GFP, a clathrin-independent cargo. Endocytosis was significantly affected by cholesterol extraction with methyl-β-cyclodextrin and inhibition of Arf6 function with dominant negative Arf6-T27N-eGFP. Taken together, we conclude that hERG undergoes clathrin-independent endocytosis via a mechanism involving Arf6. PMID:24392021

Towards a Structural View of Drug Binding to hERG K+ Channels.

Science.gov (United States)

Vandenberg, Jamie I; Perozo, Eduardo; Allen, Toby W

2017-10-01

The human ether-a-go-go-related gene (hERG) K + channel is of great medical and pharmaceutical relevance. Inherited mutations in hERG result in congenital long-QT syndrome which is associated with a markedly increased risk of cardiac arrhythmia and sudden death. hERG K + channels are also remarkably susceptible to block by a wide range of drugs, which in turn can cause drug-induced long-QT syndrome and an increased risk of sudden death. The recent determination of the near-atomic resolution structure of the hERG K + channel, using single-particle cryo-electron microscopy (cryo-EM), provides tremendous insights into how these channels work. It also suggests a way forward in our quest to understand why these channels are so promiscuous with respect to drug binding. Copyright © 2017 Elsevier Ltd. All rights reserved.

Soil Characterization at the Linde FUSRAP Site and the Impact on Soil Volume Estimates

International Nuclear Information System (INIS)

Boyle, J.; Kenna, T.; Pilon, R.

2002-01-01

The former Linde site in Tonawanda, New York is currently undergoing active remediation of Manhattan Engineering District's radiological contamination. This remediation is authorized under the Formerly Utilized Sites Remedial Action Program (FUSRAP). The focus of this paper will be to describe the impact of soil characterization efforts as they relate to soil volume estimates and project cost estimates. An additional objective is to stimulate discussion about other characterization and modeling technologies, and to provide a ''Lessons Learned'' scenario to assist in future volume estimating at other FUSRAP sites. Initial soil characterization efforts at the Linde FUSRAP site in areas known to be contaminated or suspected to be contaminated were presented in the Remedial Investigation Report for the Tonawanda Site, dated February 1993. Results of those initial characterization efforts were the basis for soil volume estimates that were used to estimate and negotiate the current remediation contract. During the course of remediation, previously unidentified areas of contamination were discovered, and additional characterization was initiated. Additional test pit and geoprobe samples were obtained at over 500 locations, bringing the total to over 800 sample locations at the 135-acre site. New data continues to be collected on a routine basis during ongoing remedial actions

[Lind tulemäe kohal : valik XX sajandi teise poole türgi luulet] / Helen Geršman

Index Scriptorium Estoniae

Geršman, Helen, 1981-

2010-01-01

Tutvustus: Lind tulemäe kohal : valik XX sajandi teise poole türgi luulet / türgi keelest tõlkinud Ly Seppel ja Andres Ehin ; koostanud Ly Seppel ; järelsõna: Andres Ehin. Tallinn : Kultuurileht, 2010. (Loomingu Raamatukogu, 1406-0515 ; 2010, 11)

[ERG diagnosis and differential diagnosis: results of examination over 6 years].

Science.gov (United States)

Stemeyer, G; Stähli, P

1996-05-01

This study reviews the patient material first from the point of view of referral diagnosis. Secondly, we focus on difficulties in selective differential diagnoses. 1501 patients underwent electroretinographic (ERG) testing from 1989 to 1994, amounting to 1815 ERG recordings, including follow-up examinations. The technique applied is full-field, single flash ERG with selective stimulation of the rod- and of the cone-systems. In 3.8% (57 cases) the ERG was performed under general anesthesia in outpatients. Tapetoretinal degenerations, toxic retinal side effects, inflammatory disease and ocular trauma represented, in this order, the major groups of referral diagnoses aside from unclear visual loss. The documentation or the exclusion of tapetoretinal degeneration represented the largest share (57%) of the application of the diagnostic procedure. 171 cases of isolated retinitis pigmentosa (RP) and 33 cases of syndromic RP were identified. Frequent and rare diagnostic entities and their differential diagnoses within this group are discussed. Inevitably, a number of diagnostic decisions remain problematic, in particular at the first examination. These diagnostic difficulties are addressed also and include the differentiation between RP sine pigmento and congenital amaurosis Leber in infants, RP with macular involvement vs. cone-rod degeneration, unilateral RP vs. postinflammatory conditions, and progressive cone dystrophy vs. achromatopsia, cone-rod degeneration or Stargardt's disease. Frequent and meaningful indications for ERG recording and difficult diagnostic decisions arise from this review of a relatively large group of patients. A number of diagnoses can hardly, if not at all be established without ERG testing. These include retinal cause of visual loss in infants, congenital amaurosis Leber, RP sine pigmento, early stages of RP, carrier status in XL RP and in choroideremia, progressive cone dystrophy, toxic retinopathy without fundus changes, retinal involvement

High yield purification of full-length functional hERG K+ channels produced in Saccharomyces cerevisiae

DEFF Research Database (Denmark)

Molbaek, Karen; Scharff-Poulsen, Peter; Hélix-Nielsen, Claus

2015-01-01

knowledge this is the first reported high-yield production and purification of full length, tetrameric and functional hERG. This significant breakthrough will be paramount in obtaining hERG crystal structures, and in establishment of new high-throughput hERG drug safety screening assays....

ERG voltage-gated K+ channels regulate excitability and discharge dynamics of the medial vestibular nucleus neurones.

Science.gov (United States)

Pessia, Mauro; Servettini, Ilenio; Panichi, Roberto; Guasti, Leonardo; Grassi, Silvarosa; Arcangeli, Annarosa; Wanke, Enzo; Pettorossi, Vito Enrico

2008-10-15

The discharge properties of the medial vestibular nucleus neurones (MVNn) critically depend on the activity of several ion channel types. In this study we show, immunohistochemically, that the voltage-gated K(+) channels ERG1A, ERG1B, ERG2 and ERG3 are highly expressed within the vestibular nuclei of P10 and P60 mice. The role played by these channels in the spike-generating mechanisms of the MVNn and in temporal information processing was investigated electrophysiologically from mouse brain slices, in vitro, by analysing the spontaneous discharge and the response to square-, ramp- and sinusoid-like intracellular DC current injections in extracellular and whole-cell patch-clamp studies. We show that more than half of the recorded MVNn were responsive to ERG channel block (WAY-123,398, E4031), displaying an increase in spontaneous activity and discharge irregularity. The response to step and ramp current injection was also modified by ERG block showing a reduction of first spike latency, enhancement of discharge rate and reduction of the slow spike-frequency adaptation process. ERG channels influence the interspike slope without affecting the spike shape. Moreover, in response to sinusoid-like current, ERG channel block caused frequency-dependent gain enhancement and phase-lead shift. Taken together, the data demonstrate that ERG channels control the excitability of MVNn, their discharge regularity and probably their resonance properties.

A prospective cross-sectional study of laparoscopic subtotal Lind fundoplication for gastro-oesophageal reflux disease--a durable and effective anti-reflux procedure.

Science.gov (United States)

Shapey, I M; Agrawal, S; Peacock, A; Super, P

2015-01-01

Laparoscopic partial fundoplication for gastro-oesophageal reflux disease (GORD) is reported to have fewer side effects when compared to Nissen fundoplication, but doubts remain over its long term durability in controlling reflux. The aim of this study was to assess outcome of symptoms for all patients presenting with GORD undergoing routine laparoscopic subtotal Lind fundoplication. All patients undergoing laparoscopic fundoplication between August, 1999 and November, 2007 performed by a single surgeon were included in the study. The anti-reflux procedure studied was laparoscopic Lind (300°) fundoplication with crural repair in all cases. Patients completed pre and post-operative questionnaires containing validated scoring systems for heartburn, gas bloat, dysphagia and overall patient satisfaction. Over the 100-month period, 320 consecutive patients underwent laparoscopic subtotal Lind fundoplication. Of these, 256 (80%) replied to the questionnaire at a mean of 31 months (range 3-96 months) following surgery. 91.4% of respondents had an improvement in heartburn symptom score with a significant reduction in score from 7.74 preoperatively to 1.25 postoperatively (preflux control (heartburn and regurgitation) from 3.49 preoperatively to 1.48 after surgery (preflux symptoms with half of these reporting their recurrence within two years following surgery. Because of this all were tested with post-operative pH testing, yet only one had a 24-h pH time outside the normal range. Overall patient satisfaction was high with a visual analogue score of 9 and 88% of the patients claimed they would have the operation again. Laparoscopic Lind fundoplication demonstrates excellent reflux control when performed routinely for all patients presenting with GORD. This technique is both durable and efficacious in controlling reflux symptoms. Copyright © 2014 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved.

Uhked naised / Kozik, Eerika; Tomingas, Triin; Sepp, Karin; Liik, Kadi; Kliimask, Katrin; Saunpere, Anne ; tekst Kärt Kross

Index Scriptorium Estoniae

2007-01-01

Mille üle oled enda juures tõeliselt uhke, mida võid enda kiituseks öelda? Küsimusele vastavad Starland Salongi omanik ja Loyd Tootmine OÜ osanik Eerika Kozik, psühholoog Triin Tomingas, Kontuur Leo Burnett projektidirektor Karin Sepp, Tallinna Ülikooli õppejõud Kadi Liik, AS Koolibri turundusjuht Katrin Kliimask ja eraettevõtja Anne Saunpere

Determinants of Isoform-Specific Gating Kinetics of hERG1 Channel: Combined Experimental and Simulation Study

Directory of Open Access Journals (Sweden)

Laura L. Perissinotti

2018-04-01

Full Text Available IKr is the rapidly activating component of the delayed rectifier potassium current, the ion current largely responsible for the repolarization of the cardiac action potential. Inherited forms of long QT syndrome (LQTS (Lees-Miller et al., 1997 in humans are linked to functional modifications in the Kv11.1 (hERG ion channel and potentially life threatening arrhythmias. There is little doubt now that hERG-related component of IKr in the heart depends on the tetrameric (homo- or hetero- channels formed by two alternatively processed isoforms of hERG, termed hERG1a and hERG1b. Isoform composition (hERG1a- vs. the b-isoform has recently been reported to alter pharmacologic responses to some hERG blockers and was proposed to be an essential factor pre-disposing patients for drug-induced QT prolongation. Very little is known about the gating and pharmacological properties of two isoforms in heart membranes. For example, how gating mechanisms of the hERG1a channels differ from that of hERG1b is still unknown. The mechanisms by which hERG 1a/1b hetero-tetramers contribute to function in the heart, or what role hERG1b might play in disease are all questions to be answered. Structurally, the two isoforms differ only in the N-terminal region located in the cytoplasm: hERG1b is 340 residues shorter than hERG1a and the initial 36 residues of hERG1b are unique to this isoform. In this study, we combined electrophysiological measurements for HEK cells, kinetics and structural modeling to tease out the individual contributions of each isoform to Action Potential formation and then make predictions about the effects of having various mixture ratios of the two isoforms. By coupling electrophysiological data with computational kinetic modeling, two proposed mechanisms of hERG gating in two homo-tetramers were examined. Sets of data from various experimental stimulation protocols (HEK cells were analyzed simultaneously and fitted to Markov-chain models (M

Data on the construction of a recombinant HEK293 cell line overexpressing hERG potassium channel and examining the presence of hERG mRNA and protein expression

Directory of Open Access Journals (Sweden)

Yi Fan Teah

2017-10-01

Full Text Available The data presented in this article are related to the research article entitled “The effects of deoxyelephantopin on the cardiac delayed rectifier potassium channel current (IKr and human ether-a-go-go-related gene (hERG expression” (Y.F. Teah, M.A. Abduraman, A. Amanah, M.I. Adenan, S.F. Sulaiman, M.L. Tan [1], which the possible hERG blocking properties of deoxyelephantopin were investigated. This article describes the construction of human embryonic kidney 293 (HEK293 cells overexpressing HERG potassium channel and verification of the presence of hERG mRNA and protein expression in this recombinant cell line.

IL-6 Overexpression in ERG-Positive Prostate Cancer Is Mediated by Prostaglandin Receptor EP2.

Science.gov (United States)

Merz, Constanze; von Mässenhausen, Anne; Queisser, Angela; Vogel, Wenzel; Andrén, Ove; Kirfel, Jutta; Duensing, Stefan; Perner, Sven; Nowak, Michael

2016-04-01

Prostate cancer is the most diagnosed cancer in men and multiple risk factors and genetic alterations have been described. The TMPRSS2-ERG fusion event and the overexpression of the transcription factor ERG are present in approximately 50% of all prostate cancer patients, however, the clinical outcome is still controversial. Prostate tumors produce various soluble factors, including the pleiotropic cytokine IL-6, regulating cellular processes such as proliferation and metastatic segregation. Here, we used prostatectomy samples in a tissue microarray format and analyzed the co-expression and the clinicopathologic data of ERG and IL-6 using immunohistochemical double staining and correlated the read-out with clinicopathologic data. Expression of ERG and IL-6 correlated strongly in prostate tissue samples. Forced expression of ERG in prostate tumor cell lines resulted in significantly increased secretion of IL-6, whereas the down-regulation of ERG decreased IL-6 secretion. By dissecting the underlying mechanism in prostate tumor cell lines we show the ERG-mediated up-regulation of the prostanoid receptors EP2 and EP3. The prostanoid receptor EP2 was overexpressed in human prostate cancer tissue. Furthermore, the proliferation rate and IL-6 secretion in DU145 cells was reduced after treatment with EP2-receptor antagonist. Collectively, our study shows that the expression of ERG in prostate cancer is linked to the expression of IL-6 mediated by the prostanoid receptor EP2. Copyright © 2016 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

A novel assessment of nefazodone-induced hERG inhibition by electrophysiological and stereochemical method

Energy Technology Data Exchange (ETDEWEB)

Shin, Dae-Seop; Park, Myoung Joo [Drug Discovery Platform Technology Research Group, Korea Research Institute of Chemical Technology, Daejeon (Korea, Republic of); Lee, Hyang-Ae [Korea Institute of Toxicology, Korea Research Institute of Chemical Technology, Daejeon (Korea, Republic of); Lee, Joo Yun; Chung, Hee-Chung; Yoo, Dae Seok; Chae, Chong Hak [Drug Discovery Platform Technology Research Group, Korea Research Institute of Chemical Technology, Daejeon (Korea, Republic of); Park, Sang-Joon [College of Veterinary Medicine, Kyungpook National University, Daegu (Korea, Republic of); Kim, Ki-Suk [Korea Institute of Toxicology, Korea Research Institute of Chemical Technology, Daejeon (Korea, Republic of); Bae, Myung Ae, E-mail: mbae@krict.re.kr [Drug Discovery Platform Technology Research Group, Korea Research Institute of Chemical Technology, Daejeon (Korea, Republic of)

2014-02-01

Nefazodone was used widely as an antidepressant until it was withdrawn from the U.S. market in 2004 due to hepatotoxicity. We have investigated methods to predict various toxic effects of drug candidates to reduce the failure rate of drug discovery. An electrophysiological method was used to assess the cardiotoxicity of drug candidates. Small molecules, including withdrawn drugs, were evaluated using a patch-clamp method to establish a database of hERG inhibition. Nefazodone inhibited hERG channel activity in our system. However, nefazodone-induced hERG inhibition indicated only a theoretical risk of cardiotoxicity. Nefazodone inhibited the hERG channel in a concentration-dependent manner with an IC{sub 50} of 45.3 nM in HEK-293 cells. Nefazodone accelerated both the recovery from inactivation and its onset. Nefazodone also accelerated steady-state inactivation, although it did not modify the voltage-dependent character. Alanine mutants of hERG S6 and pore region residues were used to identify the nefazodone-binding site on hERG. The hERG S6 point mutants Y652A and F656A largely abolished the inhibition by nefazodone. The pore region mutant S624A mildly reduced the inhibition by nefazodone but T623A had little effect. A docking study showed that the aromatic rings of nefazodone interact with Y652 and F656 via π–π interactions, while an amine interacted with the S624 residue in the pore region. In conclusion, Y652 and F656 in the S6 domain play critical roles in nefazodone binding. - Highlights: • Nefazodone inhibits hERG channels with an IC{sub 50} of 45.3 nM in HEK-293 cells. • Nefazodone blocks hERG channels by binding to the open channels. • Y652 and F656 are important for binding of nefazodone. • The aromatic rings of nefazodone interact with Y652 and F656 via π–π interactions.

Differential expression of hERG1 channel isoforms reproduces properties of native I(Kr and modulates cardiac action potential characteristics.

Directory of Open Access Journals (Sweden)

Anders Peter Larsen

Full Text Available BACKGROUND: The repolarizing cardiac rapid delayed rectifier current, I(Kr, is composed of ERG1 channels. It has been suggested that two isoforms of the ERG1 protein, ERG1a and ERG1b, both contribute to I(Kr. Marked heterogeneity in the kinetic properties of native I(Kr has been described. We hypothesized that the heterogeneity of native I(Kr can be reproduced by differential expression of ERG1a and ERG1b isoforms. Furthermore, the functional consequences of differential expression of ERG1 isoforms were explored as a potential mechanism underlying native heterogeneity of action potential duration (APD and restitution. METHODOLOGY/PRINCIPAL FINDINGS: The results show that the heterogeneity of native I(Kr can be reproduced in heterologous expression systems by differential expression of ERG1a and ERG1b isoforms. Characterization of the macroscopic kinetics of ERG1 currents demonstrated that these were dependent on the relative abundance of ERG1a and ERG1b. Furthermore, we used a computational model of the ventricular cardiomyocyte to show that both APD and the slope of the restitution curve may be modulated by varying the relative abundance of ERG1a and ERG1b. As the relative abundance of ERG1b was increased, APD was gradually shortened and the slope of the restitution curve was decreased. CONCLUSIONS/SIGNIFICANCE: Our results show that differential expression of ERG1 isoforms may explain regional heterogeneity of I(Kr kinetics. The data demonstrate that subunit dependent changes in channel kinetics are important for the functional properties of ERG1 currents and hence I(Kr. Importantly, our results suggest that regional differences in the relative abundance of ERG1 isoforms may represent a potential mechanism underlying the heterogeneity of both APD and APD restitution observed in mammalian hearts.

Stereoselective inhibition of the hERG1 potassium channel

Directory of Open Access Journals (Sweden)

Liliana eSintra Grilo

2010-11-01

Full Text Available A growing number of drugs have been shown to prolong cardiac repolarization, predisposing individuals to life-threatening ventricular arrhythmias known as Torsades de Pointes. Most of these drugs are known to interfere with the human ether à-gogo related gene 1 (hERG1 channel, whose current is one of the main determinants of action potential duration. Prolonged repolarization is reflected by lengthening of the QT interval of the electrocardiogram, as seen in the suitably named drug-induced long QT syndrome. Chirality (presence of an asymmetric atom is a common feature of marketed drugs, which can therefore exist in at least two enantiomers with distinct three-dimensional structures and possibly distinct biological fates. Both the pharmacokinetic and pharmacodynamic properties can differ between enantiomers, as well as also between individuals who take the drug due to metabolic polymorphisms. Despite the large number of reports about drugs reducing the hERG1 current, potential stereoselective contributions have only been scarcely investigated. In this review, we present a non-exhaustive list of clinically important molecules which display chiral toxicity that may be related to hERG1-blocking properties. We particularly focus on methadone cardiotoxicity, which illustrates the importance of the stereoselective effect of drug chirality as well as individual variations resulting from pharmacogenetics. Furthermore, it seems likely that, during drug development, consideration of chirality in lead optimization and systematic assessment of the hERG1 current block with all enantiomers could contribute to the reduction of the risk of drug-induced LQTS.

Advance in ERG Analysis: From Peak Time and Amplitude to Frequency, Power, and Energy

Directory of Open Access Journals (Sweden)

Mathieu Gauvin

2014-01-01

Full Text Available Purpose. To compare time domain (TD: peak time and amplitude analysis of the human photopic electroretinogram (ERG with measures obtained in the frequency domain (Fourier analysis: FA and in the time-frequency domain (continuous (CWT and discrete (DWT wavelet transforms. Methods. Normal ERGs n=40 were analyzed using traditional peak time and amplitude measurements of the a- and b-waves in the TD and descriptors extracted from FA, CWT, and DWT. Selected descriptors were also compared in their ability to monitor the long-term consequences of disease process. Results. Each method extracted relevant information but had distinct limitations (i.e., temporal and frequency resolutions. The DWT offered the best compromise by allowing us to extract more relevant descriptors of the ERG signal at the cost of lesser temporal and frequency resolutions. Follow-ups of disease progression were more prolonged with the DWT (max 29 years compared to 13 with TD. Conclusions. Standardized time domain analysis of retinal function should be complemented with advanced DWT descriptors of the ERG. This method should allow more sensitive/specific quantifications of ERG responses, facilitate follow-up of disease progression, and identify diagnostically significant changes of ERG waveforms that are not resolved when the analysis is only limited to time domain measurements.

Bentonite maturation with 'Águas de Lindóia' water (SP)

Energy Technology Data Exchange (ETDEWEB)

Torrecilha, Jefferson K.; Silva, Paulo S.C., E-mail: jeffkoy@usp.br [Instituto de Pesquisas Energéticas e Nucleares (IPEN/CNEN-SP), São Paulo, SP (Brazil)

2017-07-01

This study aims to characterize the artificial peloid obtained by maturing bentonite with Águas de Lindóia water for periods of three, six and nine months. The pH, moisture, organic matter content, loss on ignition and swelling power of matured and non-matured samples were measured for physicochemical characterization. The elemental concentration was determined by instrumental neutron activation analysis. Results showed that water adsorption capacity, organic matter and swelling power is related to the maturation time and no significant differences occurs in the elemental concentration except for Na. (author)

TMPRSS2-ERG gene fusion is not associated with outcome in patients treated by prostatectomy

Science.gov (United States)

Gopalan, Anuradha; Leversha, Margaret A.; Satagopan, Jaya M.; Zhou, Qin; Al-Ahmadie, Hikmat A.; Fine, Samson W.; Eastham, James A.; Scardino, Peter T.; Scher, Howard I.; Tickoo, Satish K.; Reuter, Victor E.; Gerald, William L.

2009-01-01

A significant number of prostate cancers have been shown to have recurrent chromosomal rearrangements resulting in the fusion of the androgen regulated TMPRSS2 promoter to a member of the ETS transcription factor family, most commonly ERG. This results in ERG overexpression which may have a direct causal role in prostate tumorigenesis or progression. However, the clinical significance of the rearrangement is unclear and, in particular, relationship to outcome has been inconsistent in recent reports. We analyzed TMPRSS2-ERG gene rearrangement status by fluorescence in situ hybridization (FISH) in 521 cases of clinically localized surgically treated prostate cancer with 95 months median follow-up and also in 40 unmatched metastases. 42% of primary tumors and 40% of metastases had rearrangements. 11% had copy number increase (CNI) of the TMPRRS2-ERG region. Rearrangement alone was associated with lower grade, but not with stage, biochemical recurrence, metastases or death. CNI with and without rearrangement was associated with high grade and advanced stage. Further, a subgroup of cancers with CNI and rearrangement by deletion, with two or more copies of the deleted locus, tended to be more clinically aggressive. DNA index assessment revealed that the majority of tumors with CNI of TMPRSS2-ERG had generalized aneuploidy/ tetraploidy in contrast to tumors without TMPRSS2-ERG CNI, which were predominantly diploid. We therefore conclude that translocation of TMPRSS2-ERG is not associated with outcome and the aggressive clinical features associated with CNI of chromosome 21 reflect generalized aneuploidy and are not due to CNI specifically of rearranged TMPRSS2-ERG. PMID:19190343

ERG review of salt constitutive law, salt stress determinations, and salt corrosion and modeling studies

International Nuclear Information System (INIS)

Balon, J.E.

1986-03-01

The Engineering Review Group (ERG) was established by the Office of Nuclear Waste Isolation (ONWI) to help evaluate engineering-related issues in the US Department of Energy's nuclear waste repository program. The August 1983 meeting of the ERG reviewed a RE/SPEC technical report containing a review of eight constitutive laws that have been proposed to model the creep of salt over the ranges of stress and temperature anticipated in a nuclear repository. This report documents the ERG's comments and recommendations on this subject and the ONWI responses to the specific points raised by the ERG

High potency inhibition of hERG potassium channels by the sodium–calcium exchange inhibitor KB-R7943

Science.gov (United States)

Cheng, Hongwei; Zhang, Yihong; Du, Chunyun; Dempsey, Christopher E; Hancox, Jules C

2012-01-01

BACKGROUND AND PURPOSE KB-R7943 is an isothiourea derivative that is used widely as a pharmacological inhibitor of sodium–calcium exchange (NCX) in experiments on cardiac and other tissue types. This study investigated KB-R7943 inhibition of hERG (human ether-à-go-go-related gene) K+ channels that underpin the cardiac rapid delayed rectifier potassium current, IKr. EXPERIMENTAL APPROACH Whole-cell patch-clamp measurements were made of hERG current (IhERG) carried by wild-type or mutant hERG channels and of native rabbit ventricular IKr. Docking simulations utilized a hERG homology model built on a MthK-based template. KEY RESULTS KB-R7943 inhibited both IhERG and native IKr rapidly on membrane depolarization with IC50 values of ∼89 and ∼120 nM, respectively, for current tails at −40 mV following depolarizing voltage commands to +20 mV. Marked IhERG inhibition also occurred under ventricular action potential voltage clamp. IhERG inhibition by KB-R7943 exhibited both time- and voltage-dependence but showed no preference for inactivated over activated channels. Results of alanine mutagenesis and docking simulations indicate that KB-R7943 can bind to a pocket formed of the side chains of aromatic residues Y652 and F656, with the compound's nitrobenzyl group orientated towards the cytoplasmic side of the channel pore. The structurally related NCX inhibitor SN-6 also inhibited IhERG, but with a markedly reduced potency. CONCLUSIONS AND IMPLICATIONS KB-R7943 inhibits IhERG/IKr with a potency that exceeds that reported previously for acute cardiac NCX inhibition. Our results also support the feasibility of benzyloxyphenyl-containing NCX inhibitors with reduced potential, in comparison with KB-R7943, to inhibit hERG. PMID:21950687

ERG promotes the maintenance of hematopoietic stem cells by restricting their differentiation

DEFF Research Database (Denmark)

Knudsen, Kasper Jermiin; Rehn, Matilda Carolina; Hasemann, Marie Sigurd

2015-01-01

The balance between self-renewal and differentiation is crucial for the maintenance of hematopoietic stem cells (HSCs). Whereas numerous gene regulatory factors have been shown to control HSC self-renewal or drive their differentiation, we have relatively few insights into transcription factors...... and functional HSCs. Molecularly, we could demonstrate that ERG, in addition to promoting the expression of HSC self-renewal genes, also represses a group of MYC targets, thereby explaining why Erg loss closely mimics Myc overexpression. Consistently, the BET domain inhibitor CPI-203, known to repress Myc...... expression, confers a partial phenotypic rescue. In summary, ERG plays a critical role in coordinating the balance between self-renewal and differentiation of HSCs....

ERG [Engineering Review Group] review of the SRP [Salt Repository Project] salt irradiation effects program: Technical report

International Nuclear Information System (INIS)

Clark, D.E.

1986-11-01

The Engineering Review Group (ERG) was established by the Office of Nuclear Waste Isolation (ONWI) to help evaluate engineering-related issues in the US Department of Energy's nuclear waste repository program. The August 1985 meeting of the ERG reviewed the Salt Repository Project (SRP) salt irradiation effects program. This report documents the ERG's comments and recommendations on these subjects and the ONWI response to the specific points raised by the ERG

An ERG channel inhibitor from the scorpion Buthus eupeus

DEFF Research Database (Denmark)

Korolkova, Y.V.; Kozlov, S.A.; Lipkin, A.V.

2001-01-01

and the three mutants partly inhibited the native M-like current in NG108-15 at 100 nm. The effect of the recombinant BeKm-1 on different K(+) channels was also studied. BeKm-1 inhibited hERG1 channels with an IC(50) of 3.3 nm, but had no effect at 100 nm on hEAG, hSK1, rSK2, hIK, hBK, KCNQ1/KCNE1, KCNQ2/KCNQ3......, KCNQ4 channels, and minimal effect on rELK1. Thus, BeKm-1 was shown to be a novel specific blocker of hERG1 potassium channels....

Transcription factor ERG and joint and articular cartilage formation during mouse limb and spine skeletogenesis.

Science.gov (United States)

Iwamoto, Masahiro; Tamamura, Yoshihiro; Koyama, Eiki; Komori, Toshihisa; Takeshita, Nobuo; Williams, Julie A; Nakamura, Takashi; Enomoto-Iwamoto, Motomi; Pacifici, Maurizio

2007-05-01

Articular cartilage and synovial joints are critical for skeletal function, but the mechanisms regulating their development are largely unknown. In previous studies we found that the ets transcription factor ERG and its alternatively-spliced variant C-1-1 have roles in joint formation in chick. Here, we extended our studies to mouse. We found that ERG is also expressed in developing mouse limb joints. To test regulation of ERG expression, beads coated with the joint master regulator protein GDF-5 were implanted close to incipient joints in mouse limb explants; this led to rapid and strong ectopic ERG expression. We cloned and characterized several mammalian ERG variants and expressed a human C-1-1 counterpart (hERG3Delta81) throughout the cartilaginous skeleton of transgenic mice, using Col2a1 gene promoter/enhancer sequences. The skeletal phenotype was severe and neonatal lethal, and the transgenic mice were smaller than wild type littermates and their skeletons were largely cartilaginous. Limb long bone anlagen were entirely composed of chondrocytes actively expressing collagen IX and aggrecan as well as articular markers such as tenascin-C. Typical growth plates were absent and there was very low expression of maturation and hypertrophy markers, including Indian hedgehog, collagen X and MMP-13. The results suggest that ERG is part of molecular mechanisms leading chondrocytes into a permanent developmental path and become joint forming cells, and may do so by acting downstream of GDF-5.

Structural implications of hERG K+ channel block by a high-affinity minimally structured blocker

Science.gov (United States)

Helliwell, Matthew V.; Zhang, Yihong; El Harchi, Aziza; Du, Chunyun; Hancox, Jules C.; Dempsey, Christopher E.

2018-01-01

Cardiac potassium channels encoded by human ether-à-go-go–related gene (hERG) are major targets for structurally diverse drugs associated with acquired long QT syndrome. This study characterized hERG channel inhibition by a minimally structured high-affinity hERG inhibitor, Cavalli-2, composed of three phenyl groups linked by polymethylene spacers around a central amino group, chosen to probe the spatial arrangement of side chain groups in the high-affinity drug-binding site of the hERG pore. hERG current (IhERG) recorded at physiological temperature from HEK293 cells was inhibited with an IC50 of 35.6 nm with time and voltage dependence characteristic of blockade contingent upon channel gating. Potency of Cavalli-2 action was markedly reduced for attenuated inactivation mutants located near (S620T; 54-fold) and remote from (N588K; 15-fold) the channel pore. The S6 Y652A and F656A mutations decreased inhibitory potency 17- and 75-fold, respectively, whereas T623A and S624A at the base of the selectivity filter also decreased potency (16- and 7-fold, respectively). The S5 helix F557L mutation decreased potency 10-fold, and both F557L and Y652A mutations eliminated voltage dependence of inhibition. Computational docking using the recent cryo-EM structure of an open channel hERG construct could only partially recapitulate experimental data, and the high dependence of Cavalli-2 block on Phe-656 is not readily explainable in that structure. A small clockwise rotation of the inner (S6) helix of the hERG pore from its configuration in the cryo-EM structure may be required to optimize Phe-656 side chain orientations compatible with high-affinity block. PMID:29545312

Increased adipogenesis in cultured embryonic chondrocytes and in adult bone marrow of dominant negative Erg transgenic mice.

Directory of Open Access Journals (Sweden)

Sébastien Flajollet

Full Text Available In monolayer culture, primary articular chondrocytes have an intrinsic tendency to lose their phenotype during expansion. The molecular events underlying this chondrocyte dedifferentiation are still largely unknown. Several transcription factors are important for chondrocyte differentiation. The Ets transcription factor family may be involved in skeletal development. One family member, the Erg gene, is mainly expressed during cartilage formation. To further investigate the potential role of Erg in the maintenance of the chondrocyte phenotype, we isolated and cultured chondrocytes from the rib cartilage of embryos of transgenic mice that express a dominant negative form of Erg (DN-Erg during cartilage formation. DN-Erg expression in chondrocytes cultured for up to 20 days did not affect the early dedifferentiation usually observed in cultured chondrocytes. However, lipid droplets accumulated in DN-Erg chondrocytes, suggesting adipocyte emergence. Transcriptomic analysis using a DNA microarray, validated by quantitative RT-PCR, revealed strong differential gene expression, with a decrease in chondrogenesis-related markers and an increase in adipogenesis-related gene expression in cultured DN-Erg chondrocytes. These results indicate that Erg is involved in either maintaining the chondrogenic phenotype in vitro or in cell fate orientation. Along with the in vitro studies, we compared adipocyte presence in wild-type and transgenic mice skeletons. Histological investigations revealed an increase in the number of adipocytes in the bone marrow of adult DN-Erg mice even though no adipocytes were detected in embryonic cartilage or bone. These findings suggest that the Ets transcription factor family may contribute to the homeostatic balance in skeleton cell plasticity.

Early identification of hERG liability in drug discovery programs by automated patch clamp

Directory of Open Access Journals (Sweden)

Timm eDanker

2014-09-01

Full Text Available Blockade of the cardiac ion channel coded by hERG can lead to cardiac arrhythmia, which has become a major concern in drug discovery and development. Automated electrophysiological patch clamp allows assessment of hERG channel effects early in drug development to aid medicinal chemistry programs and has become routine in pharmaceutical companies. However, a number of potential sources of errors in setting up hERG channel assays by automated patch clamp can lead to misinterpretation of data or false effects being reported. This article describes protocols for automated electrophysiology screening of compound effects on the hERG channel current. Protocol details and the translation of criteria known from manual patch clamp experiments to automated patch clamp experiments to achieve good quality data are emphasized. Typical pitfalls and artifacts that may lead to misinterpretation of data are discussed. While this article focuses on hERG channel recordings using the QPatch (Sophion A/S, Copenhagen, Denmark technology, many of the assay and protocol details given in this article can be transferred for setting up different ion channel assays by automated patch clamp and are similar on other planar patch clamp platforms.

[Effects of pressure induced retinal ischemia on ERG in rabbit].

Science.gov (United States)

Song, G; Yang, X; Zhang, Z; Zhang, D

2001-12-01

To observe the effects of pressure induced retinal ischemia on electroretinogram(ERG) in rabbit. Retinal ischemia was induced in rabbits by increasing intraocular pressure at 30 mmHg, 60 mmHg, 90 mmHg, 120 mmHg for 45 minutes, and retinal function was monitored by eletroretinography. There was no difference on ERG before or after the experiment both in 30 mmHg group and control one. In 60 mmHg pressure induced ischemia eyes, the amplitudes of the b-wave and OPs wave reduced significantly. Four hours after reperfusion, they were totally recovered. After an ischemic insult of 90 mmHg or 120 mmHg for 45 minutes, there was no response of ERG. Four hours later, the amplitudes of the b-wave and OPs wave were 66.912 +/- 20.157 and 16.423 +/- 3.965 the former, 38.852 +/- 23.438 and 8.610 +/- 12.090 the latter, respectively. These results suggest that higher intraocular pressure causes more severe retina ischemic damage, and less recovery ability.

TMPRSS2- driven ERG expression in vivo increases self-renewal and maintains expression in a castration resistant subpopulation.

Directory of Open Access Journals (Sweden)

Orla M Casey

Full Text Available Genomic rearrangements commonly occur in many types of cancers and often initiate or alter the progression of disease. Here we describe an in vivo mouse model that recapitulates the most frequent rearrangement in prostate cancer, the fusion of the promoter region of TMPRSS2 with the coding region of the transcription factor, ERG. A recombinant bacterial artificial chromosome including an extended TMPRSS2 promoter driving genomic ERG was constructed and used for transgenesis in mice. TMPRSS2-ERG expression was evaluated in tissue sections and FACS-fractionated prostate cell populations. In addition to the anticipated expression in luminal cells, TMPRSS2-ERG was similarly expressed in the Sca-1(hi/EpCAM(+ basal/progenitor fraction, where expanded numbers of clonogenic self-renewing progenitors were found, as assayed by in vitro sphere formation. These clonogenic cells increased intrinsic self renewal in subsequent generations. In addition, ERG dependent self-renewal and invasion in vitro was demonstrated in prostate cell lines derived from the model. Clinical studies have suggested that the TMPRSS2-ERG translocation occurs early in prostate cancer development. In the model described here, the presence of the TMPRSS2-ERG fusion alone was not transforming but synergized with heterozygous Pten deletion to promote PIN. Taken together, these data suggest that one function of TMPRSS2-ERG is the expansion of self-renewing cells, which may serve as targets for subsequent mutations. Primary prostate epithelial cells demonstrated increased post transcriptional turnover of ERG compared to the TMPRSS2-ERG positive VCaP cell line, originally isolated from a prostate cancer metastasis. Finally, we determined that TMPRSS2-ERG expression occurred in both castration-sensitive and resistant prostate epithelial subpopulations, suggesting the existence of androgen-independent mechanisms of TMPRSS2 expression in prostate epithelium.

Children with complete or incomplete congenital stationary night blindness: ophthalmological findings, standard ERGs and ON-OFF ERGs for differentiation between types

Directory of Open Access Journals (Sweden)

Maja Šuštar

2012-06-01

Conclusion: Distinct electrophysiological characteristics can be used to differentiate between complete and incomplete CSNB. Moreover, ONOFF ERGs are important for precise localization of the retinal bipolar cell dysfunction, and these can also be reliably recorded in children.

Pharmacologic Approach to Defective Protein Trafficking in the E637K-hERG Mutant with PD-118057 and Thapsigargin.

Directory of Open Access Journals (Sweden)

Haiyan Mao

Full Text Available Treatment of LQT2 is inadequate. Many drugs which can pharmacologically rescue defective protein trafficking in LQT2 also result in potent blockade of HERG current, negating their therapeutic benefit. It is reported that PD-118057 and thapsigargin can rescue LQT2 without hERG channel blockade, but the precise mechanism of action is unknown. Furthermore, the effect of PD-118057 and thapsigargin on the dominant negative E637K-hERG mutant has not been previously investigated.IN THIS STUDY, WE INVESTIGATED: (a the effect of PD-118057 and thapsigargin on the current amplitudes of WT-hERG and WT/E637K-hERG channels; (b the effect of PD-118057 and thapsigargin on the biophysical properties of WT-hERG and WT/E637K-hERG channels; (c whether drug treatment can rescue channel processing and trafficking defects of the WT/E637K-hERG mutant.The whole-cell Patch-clamp technique was used to assess the effect of PD-118057 and thapsigargin on the electrophysiological characteristics of the rapidly activating delayed rectifier K(+ current (Ikr of the hERG protein channel. Western blot was done to investigate pharmacological rescue on hERG protein channel function.In our study, PD-118057 was shown to significantly enhance both the maximum current amplitude and tail current amplitude, but did not alter the gating and kinetic properties of the WT-hERG channel, with the exception of accelerating steady-state inactivation. Additionally, thapsigargin shows a similar result as PD-118057 for the WT-hERG channel, but with the exception of attenuating steady-state inactivation. However, for the WT/E637K-hERG channel, PD-118057 had no effect on either the current or on the gating and kinetic properties. Furthermore, thapsigargin treatment did not alter the current or the gating and kinetic properties of the WT/E637K-hERG channel, with the exception of opening at more positive voltages.Our findings illustrate that neither PD-118057 nor thapsigargin play a role in correcting

Structure and Function of the Splice Variants of TMPRSS2-ERG, a Prevalent Genomic Alteration in Prostate Cancer

Science.gov (United States)

2012-09-01

expression in prostate cancer (4). Lower or no ERG expression in a subset of aggressive tumors with TMPRSS2-ERG fusion may reflect attenuation of androgen...Services University of the Health Sciences, Bethesda MD 20814, USA 2. Cancer Vaccine Development Laboratory, Department of Surgery, United...negative for ERG. The ERG MAb did not show cross reactivity to FLI-1 in LNCaP cells infected with a FLI-1 adenovirus expression vector (Fig 1A

Research priorities in mesothelioma: A James Lind Alliance Priority Setting Partnership.

Science.gov (United States)

Stephens, R J; Whiting, C; Cowan, K

2015-08-01

In the UK, despite the import and use of all forms of asbestos being banned more than 15 years ago, the incidence of mesothelioma continues to rise. Mesothelioma is almost invariably fatal, and more research is required, not only to find more effective treatments, but also to achieve an earlier diagnosis and improve palliative care. Following a debate in the House of Lords in July 2013, a package of measures was agreed, which included a James Lind Alliance Priority Setting Partnership, funded by the National Institute for Health Research. The partnership brought together patients, carers, health professionals and support organisations to agree the top 10 research priorities relating to the diagnosis, treatment and care of patients with mesothelioma. Following the established James Lind Alliance priority setting process, mesothelioma patients, current and bereaved carers, and health professionals were surveyed to elicit their concerns regarding diagnosis, treatment and care. Research questions were generated from the survey responses, and following checks that the questions were currently unanswered, an interim prioritisation survey was conducted to identify a shortlist of questions to take to a final consensus meeting. Four hundred and fifty-three initial surveys were returned, which were refined into 52 unique unanswered research questions. The interim prioritisation survey was completed by 202 responders, and the top 30 questions were taken to a final meeting where mesothelioma patients, carers, and health professionals prioritised all the questions, and reached a consensus on the top 10. The top 10 questions cover a wide portfolio of research (including assessing the value of immunotherapy, individualised chemotherapy, second-line treatment and immediate chemotherapy, monitoring patients with pleural thickening, defining the management of ascites in peritoneal mesothelioma, and optimising follow-up strategy). This list is an invaluable resource, which should be

Mechanisms of IhERG/IKr Modulation by α1-Adrenoceptors in HEK293 Cells and Cardiac Myocytes

Directory of Open Access Journals (Sweden)

Janire Urrutia

2016-12-01

Full Text Available Background: The rapid delayed rectifier K+ current (IKr, carried by the hERG protein, is one of the main repolarising currents in the human heart and a reduction of this current increases the risk of ventricular fibrillation. α1-adrenoceptors (α1-AR activation reduces IKr but, despite the clear relationship between an increase in the sympathetic tone and arrhythmias, the mechanisms underlying the α1-AR regulation of the hERG channel are controversial. Thus, we aimed to investigate the mechanisms by which α1-AR stimulation regulates IKr. Methods: α1-adrenoceptors, hERG channels, auxiliary subunits minK and MIRP1, the non PIP2-interacting mutant D-hERG (with a deletion of the 883-894 amino acids in the C-terminal and the non PKC-phosphorylable mutant N-terminal truncated-hERG (NTK-hERG were transfected in HEK293 cells. Cell membranes were extracted by centrifugation and the different proteins were visualized by Western blot. Potassium currents were recorded by the patch-clamp technique. IKr was recorded in isolated feline cardiac myocytes. Results: Activation of the α1-AR reduces the amplitude of IhERG and IKr through a positive shift in the activation half voltage, which reduces the channel availability at physiological membrane potentials. The intracellular pathway connecting the α1-AR to the hERG channel in HEK293 cells includes activation of the Gαq protein, PLC activation and PIP2 hydrolysis, activation of PKC and direct phosphorylation of the hERG channel N-terminal. The PKC-mediated IKr channel phosphorylation and subsequent IKr reduction after α1-AR stimulation was corroborated in feline cardiac myocytes. Conclusions: These findings clarify the link between sympathetic nervous system hyperactivity and IKr reduction, one of the best characterized causes of torsades de pointes and ventricular fibrillation.

A DNA methylation microarray-based study identifies ERG as a gene commonly methylated in prostate cancer.

Science.gov (United States)

Schwartzman, Jacob; Mongoue-Tchokote, Solange; Gibbs, Angela; Gao, Lina; Corless, Christopher L; Jin, Jennifer; Zarour, Luai; Higano, Celestia; True, Lawrence D; Vessella, Robert L; Wilmot, Beth; Bottomly, Daniel; McWeeney, Shannon K; Bova, G Steven; Partin, Alan W; Mori, Motomi; Alumkal, Joshi

2011-10-01

DNA methylation of promoter regions is a common event in prostate cancer, one of the most common cancers in men worldwide. Because prior reports demonstrating that DNA methylation is important in prostate cancer studied a limited number of genes, we systematically quantified the DNA methylation status of 1505 CpG dinucleotides for 807 genes in 78 paraffin-embedded prostate cancer samples and three normal prostate samples. The ERG gene, commonly repressed in prostate cells in the absence of an oncogenic fusion to the TMPRSS2 gene, was one of the most commonly methylated genes, occurring in 74% of prostate cancer specimens. In an independent group of patient samples, we confirmed that ERG DNA methylation was common, occurring in 57% of specimens, and cancer-specific. The ERG promoter is marked by repressive chromatin marks mediated by polycomb proteins in both normal prostate cells and prostate cancer cells, which may explain ERG's predisposition to DNA methylation and the fact that tumors with ERG DNA methylation were more methylated, in general. These results demonstrate that bead arrays offer a high-throughput method to discover novel genes with promoter DNA methylation such as ERG, whose measurement may improve our ability to more accurately detect prostate cancer.

Geospace exploration project: Arase (ERG)

Science.gov (United States)

Miyoshi, Y.; Kasaba, Y.; Shinohara, I.; Takashima, T.; Asamura, K.; Matsumoto, H.; Higashio, N.; Mitani, T.; Kasahara, S.; Yokota, S.; Wang, S.; Kazama, Y.; Kasahara, Y.; Yagitani, S.; Matsuoka, A.; Kojima, H.; Katoh, Y.; Shiokawa, K.; Seki, K.; Fujimoto, M.; Ono, T.; ERG project Group

2017-06-01

The ERG (Exploration of energization and Radiation in Geospace) is Japanese geospace exploration project. The project focuses on relativistic electron acceleration mechanism of the outer belt and dynamics of space storms in the context of the cross-energy coupling via wave-particle interactions. The project consists of the satellite observation team, the ground-based network observation team, and integrated-data analysis/simulation team. The satellite was launched on December 20 2016 and has been nicknamed, “Arase”. This paper describes overview of the project and future plan for observations.

Concurrent nuclear ERG and MYC protein overexpression defines a subset of locally advanced prostate cancer: Potential opportunities for synergistic targeted therapeutics.

Science.gov (United States)

Udager, Aaron M; DeMarzo, Angelo M; Shi, Yang; Hicks, Jessica L; Cao, Xuhong; Siddiqui, Javed; Jiang, Hui; Chinnaiyan, Arul M; Mehra, Rohit

2016-06-01

Recurrent ERG gene fusions, the most common genetic alterations in prostate cancer, drive overexpression of the nuclear transcription factor ERG, and are early clonal events in prostate cancer progression. The nuclear transcription factor MYC is also frequently overexpressed in prostate cancer and may play a role in tumor initiation and/or progression. The relationship between nuclear ERG and MYC protein overexpression in prostate cancer, as well as the clinicopathologic characteristics and prognosis of ERG-positive/MYC high tumors, is not well understood. Immunohistochemistry (IHC) for ERG and MYC was performed on formalin-fixed, paraffin-embedded tissue from prostate cancer tissue microarrays (TMAs), and nuclear staining was scored semi-quantitatively (IHC product score range = 0-300). Correlation between nuclear ERG and MYC protein expression and association with clinicopathologic parameters and biochemical recurrence after radical prostatectomy was assessed. 29.1% of all tumor nodules showed concurrent nuclear ERG and MYC protein overexpression (i.e., ERG-positive/MYC high), including 35.0% of secondary nodules. Overall, there was weak positive correlation between ERG and MYC expression across all tumor nodules (rpb  = 0.149, P = 0.045), although this correlation was strongest in secondary nodules (rpb  = 0.520, P = 0.019). In radical prostatectomy specimens, ERG-positive/MYC high tumors were positively associated with the presence of extraprostatic extension (EPE), relative to all other ERG/MYC expression subgroups, however, there was no significant association between concurrent nuclear ERG and MYC protein overexpression and time to biochemical recurrence. Concurrent nuclear ERG and MYC protein overexpression is common in prostate cancer and defines a subset of locally advanced tumors. Recent data indicates that BET bromodomain proteins regulate ERG gene fusion and MYC gene expression in prostate cancer, suggesting possible synergistic

Developing a PTEN-ERG Signature to Improve Molecular Risk Stratification in Prostate Cancer

Science.gov (United States)

2017-10-01

performed exploratory data analysis on all clinically annotated prostate cancer datasets available from the public domain and through the collaboration...with GenomeDX. We used statistical summaries and data visualizations techniques (e.g., principal component analysis , hierarchical clustering) to...associated with PTEN loss on genetically homogeneous ERG-positive and ERG- negative backgrounds. Timeline (Months) Major Task 2: Perform CAGE analysis

Overcoming hERG affinity in the discovery of maraviroc; a CCR5 antagonist for the treatment of HIV.

Science.gov (United States)

Price, David A; Armour, Duncan; de Groot, Marcel; Leishman, Derek; Napier, Carolyn; Perros, Manos; Stammen, Blanda L; Wood, Anthony

2008-01-01

Avoiding cardiac liability associated with blockade of hERG (human ether a go-go) is key for successful drug discovery and development. This paper describes the work undertaken in the discovery of a potent CCR5 antagonist, maraviroc 34, for the treatment of HIV. In particular the use of a pharmacophore model of the hERG channel and a high throughput binding assay for the hERG channel are described that were critical to elucidate SAR to overcome hERG liabilities. The key SAR involves the introduction of polar substituents into regions of the molecule where it is postulated to undergo hydrophobic interactions with the ion channel. Within the CCR5 project there appeared to be no strong correlation between hERG affinity and physiochemical parameters such as pKa or lipophilicity. It is believed that chemists could apply these same strategies early in drug discovery to remove hERG interactions associated with lead compounds while retaining potency at the primary target.

Differential expression of hERG1 channel isoforms reproduces properties of native I(Kr) and modulates cardiac action potential characteristics

DEFF Research Database (Denmark)

Larsen, Anders Peter; Olesen, Søren-Peter

2010-01-01

The repolarizing cardiac rapid delayed rectifier current, I(Kr), is composed of ERG1 channels. It has been suggested that two isoforms of the ERG1 protein, ERG1a and ERG1b, both contribute to I(Kr). Marked heterogeneity in the kinetic properties of native I(Kr) has been described. We hypothesized...

Feasibility study of a dedicate nuclear desalination system: Low-pressure inherent heat sink nuclear desalination plant (LIND)

Energy Technology Data Exchange (ETDEWEB)

Kim, Ho Sik; No, Hee Cheon; Jo, Yu Gwan; Wivisono, Andhika Feri; Park, Byung Ha; Choi, Jin Young; Lee, Jeong Ik; Jeong, Yong Hoon; Cho, Nam Zin [Dept. of Nuclear and Quantum Engineering, Korea Advanced Institute of Science and Technology, Daejeon (Korea, Republic of)

2015-04-15

In this paper, we suggest the conceptual design of a water-cooled reactor system for a low-pressure inherent heat sink nuclear desalination plant (LIND) that applies the safety-related design concepts of high temperature gas-cooled reactors to a water-cooled reactor for inherent and passive safety features. Through a scoping analysis, we found that the current LIND design satisfied several essential thermal-hydraulic and neutronic design requirements. In a thermal-hydraulic analysis using an analytical method based on the Wooton-Epstein correlation, we checked the possibility of safely removing decay heat through the steel containment even if all the active safety systems failed. In a neutronic analysis using the Monte Carlo N-particle transport code, we estimated a cycle length of approximately 6 years under 200 MW{sub th} and 4.5% enrichment. The very long cycle length and simple safety features minimize the burdens from the operation, maintenance, and spent-fuel management, with a positive impact on the economic feasibility. Finally, because a nuclear reactor should not be directly coupled to a desalination system to prevent the leakage of radioactive material into the desalinated water, three types of intermediate systems were studied: a steam producing system, a hot water system, and an organic Rankine cycle system.

Feasibility study of a dedicated nuclear desalination system: Low-pressure Inherent heat sink Nuclear Desalination plant (LIND

Directory of Open Access Journals (Sweden)

Ho Sik Kim

2015-04-01

Full Text Available In this paper, we suggest the conceptual design of a water-cooled reactor system for a low-pressure inherent heat sink nuclear desalination plant (LIND that applies the safety-related design concepts of high temperature gas-cooled reactors to a water-cooled reactor for inherent and passive safety features. Through a scoping analysis, we found that the current LIND design satisfied several essential thermal–hydraulic and neutronic design requirements. In a thermal–hydraulic analysis using an analytical method based on the Wooton–Epstein correlation, we checked the possibility of safely removing decay heat through the steel containment even if all the active safety systems failed. In a neutronic analysis using the Monte Carlo N-particle transport code, we estimated a cycle length of approximately 6 years under 200 MWth and 4.5% enrichment. The very long cycle length and simple safety features minimize the burdens from the operation, maintenance, and spent-fuel management, with a positive impact on the economic feasibility. Finally, because a nuclear reactor should not be directly coupled to a desalination system to prevent the leakage of radioactive material into the desalinated water, three types of intermediate systems were studied: a steam producing system, a hot water system, and an organic Rankine cycle system.

TMPRSS2-ERG gene fusions are infrequent in prostatic ductal adenocarcinomas.

Science.gov (United States)

Lotan, Tamara L; Toubaji, Antoun; Albadine, Roula; Latour, Mathieu; Herawi, Mehsati; Meeker, Alan K; DeMarzo, Angelo M; Platz, Elizabeth A; Epstein, Jonathan I; Netto, George J

2009-03-01

Ductal adenocarcinoma of the prostate is an unusual subtype that may be associated with a more aggressive clinical course, and is less responsive to conventional therapies than the more common prostatic acinar adenocarcinoma. However, given its frequent association with an acinar component at prostatectomy, some have challenged the concept of prostatic ductal adenocarcinoma as a distinct clinicopathologic entity. We studied the occurrence of the TMPRSS2-ERG gene fusion, in 40 surgically resected ductal adenocarcinoma cases, and in their associated acinar component using fluorescence in situ hybridization. A group of 38 'pure' acinar adenocarcinoma cases matched with the ductal adenocarcinoma group for pathological grade and stage was studied as a control. Compared with the matched acinar adenocarcinoma cases, the TMPRSS2-ERG gene fusion was significantly less frequently observed in ductal adenocarcinoma (45 vs 11% of cases, P=0.002, Fisher's exact test). Here, of the ductal adenocarcinoma cases with the gene fusion, 75% were fused through deletion, and the remaining case was fused through translocation. The TMPRSS2-ERG gene fusion was also rare in the acinar component of mixed ductal-acinar tumors when compared with the pure acinar adenocarcinoma controls (5 vs 45%, P=0.001, Fisher's exact test). In 95% of the ductal adenocarcinoma cases in which a concurrent acinar component was analyzed, there was concordance for presence/absence of the TMPRSS2-ERG gene fusion between the different histologic subtypes. In the control group of pure acinar adenocarcinoma cases, 59% were fused through deletion and 41% were fused through translocation. The presence of the TMPRSS2-ERG gene fusion in some cases of prostatic ductal adenocarcinoma supports the concept that ductal adenocarcinoma and acinar adenocarcinoma may be related genetically. However, the significantly lower rate of the gene fusion in pure ductal adenocarcinoma cases underscores the fact that genetic and biologic

Role of the pH in state-dependent blockade of hERG currents

Science.gov (United States)

Wang, Yibo; Guo, Jiqing; Perissinotti, Laura L.; Lees-Miller, James; Teng, Guoqi; Durdagi, Serdar; Duff, Henry J.; Noskov, Sergei Yu.

2016-10-01

Mutations that reduce inactivation of the voltage-gated Kv11.1 potassium channel (hERG) reduce binding for a number of blockers. State specific block of the inactivated state of hERG block may increase risks of drug-induced Torsade de pointes. In this study, molecular simulations of dofetilide binding to the previously developed and experimentally validated models of the hERG channel in open and open-inactivated states were combined with voltage-clamp experiments to unravel the mechanism(s) of state-dependent blockade. The computations of the free energy profiles associated with the drug block to its binding pocket in the intra-cavitary site display startling differences in the open and open-inactivated states of the channel. It was also found that drug ionization may play a crucial role in preferential targeting to the open-inactivated state of the pore domain. pH-dependent hERG blockade by dofetilie was studied with patch-clamp recordings. The results show that low pH increases the extent and speed of drug-induced block. Both experimental and computational findings indicate that binding to the open-inactivated state is of key importance to our understanding of the dofetilide’s mode of action.

A radiolabeled peptide ligand of the hERG channel, [125I]-BeKm-1

DEFF Research Database (Denmark)

Angelo, Kamilla; Korolkova, Yuliya V; Grunnet, Morten

2003-01-01

The wild-type scorpion toxin BeKm-1, which selectively blocks human ether-a-go-go related (hERG) channels, was radiolabeled with iodine at tyrosine 11. Both the mono- and di-iodinated derivatives were found to be biologically active. In electrophysiological patch-clamp recordings mono-[127I]-BeKm-1...... had a concentration of half-maximal inhibition (IC50 value) of 27 nM, while wild-type BeKm-1 inhibited hERG channels with an IC50 value of 7 nM. Mono-[125I]-BeKm-1 was found to bind in a concentration-dependent manner and with picomolar affinity to hERG channel protein in purified membrane vesicles...... of [125I]-BeKm-1 to the hERG channel to an IC50 of 7 nM. In autoradiographic studies on rat hearts, binding of [125I]-BeKm-1 was dose-dependent and could partially be displaced by the addition of excess amounts of non-radioactive BeKm-1. The density of the radioactive signal was equally distributed...

RhoJ is an endothelial cell-restricted Rho GTPase that mediates vascular morphogenesis and is regulated by the transcription factor ERG

NARCIS (Netherlands)

Yuan, Lei; Sacharidou, Anastasia; Stratman, Amber N.; Le Bras, Alexandra; Zwiers, Peter J.; Spokes, Katherine; Bhasin, Manoj; Shih, Shou-ching; Nagy, Janice A.; Molema, Grietje; Aird, William C.; Davis, George E.; Oettgen, Peter

2011-01-01

ERG is a member of the ETS transcription factor family that is highly enriched in endothelial cells (ECs). To further define the role of ERG in regulating EC function, we evaluated the effect of ERG knockdown on EC lumen formation in 3D collagen matrices. Blockade of ERG using siRNA completely

ERG review of ''draft test plan for in situ testing in an exploratory shaft in salt - March 1985''

International Nuclear Information System (INIS)

Byrne, R.J.

1986-08-01

The Engineering Review Group (ERG) was established by the Office of Nuclear Waste Isolation (ONWI) to help evaluate engineering-related issues in the US Department of Energy's nuclear waste repository program. The May 1985 meeting of the ERG reviewed the proposed program which constitutes part of the overall effort to determine site suitability, provide data for repository design and performance assessment, and prepare licensing documentation for radioactive waste disposal in salt. This report documents the ERG's comments and recommendations on these subjects and the ONWI response, prepared by Golder Associates, Inc., to the specific points raised by the ERG

Targeting TMPRSS2 ERG in Prostate Cancer

Science.gov (United States)

2016-09-01

kinome library, using physiologic cell based assays of ERG activity. We made lentivirus expressing multiple shRNAs targeting each candidate 9...MDV3100 reverses the effect of R1881 (compare columns 2 and 3). Interestingly, PKCi inhibited a subset of androgen induced genes ( column 4...expenditures Nothing to report. Significant changes in use or care of human subjects, vertebrate animals, biohazards, and/or select agents Nothing to

Modeling of the hERG K+ Channel Blockage Using Online Chemical Database and Modeling Environment (OCHEM).

Science.gov (United States)

Li, Xiao; Zhang, Yuan; Li, Huanhuan; Zhao, Yong

2017-12-01

Human ether-a-go-go related gene (hERG) K+ channel plays an important role in cardiac action potential. Blockage of hERG channel may result in long QT syndrome (LQTS), even cause sudden cardiac death. Many drugs have been withdrawn from the market because of the serious hERG-related cardiotoxicity. Therefore, it is quite essential to estimate the chemical blockage of hERG in the early stage of drug discovery. In this study, a diverse set of 3721 compounds with hERG inhibition data was assembled from literature. Then, we make full use of the Online Chemical Modeling Environment (OCHEM), which supplies rich machine learning methods and descriptor sets, to build a series of classification models for hERG blockage. We also generated two consensus models based on the top-performing individual models. The consensus models performed much better than the individual models both on 5-fold cross validation and external validation. Especially, consensus model II yielded the prediction accuracy of 89.5 % and MCC of 0.670 on external validation. This result indicated that the predictive power of consensus model II should be stronger than most of the previously reported models. The 17 top-performing individual models and the consensus models and the data sets used for model development are available at https://ochem.eu/article/103592. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Developing a PTEN-ERG Signature to Improve Molecular Risk Stratification in Prostate Cancer

Science.gov (United States)

2017-10-01

AWARD NUMBER: W81XWH-16-1-0737 TITLE: Developing a PTEN-ERG Signature to Improve Molecular Risk Stratification in Prostate Cancer PRINCIPAL...AND SUBTITLE 5a. CONTRACT NUMBER Developing a PTEN-ERG Signature to Improve Molecular Risk Stratification in Prostate Cancer 5b. GRANT NUMBER W81XWH...that there exist distinctive molecular correlates of PTEN loss in the context of ETS-negative versus ETS-positive human prostate cancers and that

Research priorities for shoulder surgery: results of the 2015 James Lind Alliance patient and clinician priority setting partnership.

Science.gov (United States)

Rangan, Amar; Upadhaya, Sheela; Regan, Sandra; Toye, Francine; Rees, Jonathan L

2016-04-11

To run a UK based James Lind Alliance Priority Setting Partnership for 'Surgery for Common Shoulder Problems'. This was a nationally funded and conducted process. It was organised from a musculoskeletal research centre and Biomedical Research Unit in Oxford. UK shoulder patients, carers and clinicians, involved in treating patients with shoulder pain and shoulder problems that might require surgery. These were national electronic and paper surveys capturing treatment uncertainties that are important to shoulder patients, carers and clinicians. The outcomes relevant to this study were the survey results and rankings. The process took 18 months to complete, with 371 participants contributing 404 in scope questions. The James Lind process then produced a final 10 research priorities and uncertainties that relate to the scope of 'Surgery for Common Shoulder Problems'. The final top 10 UK research priorities have been produced and are now being disseminated to partner organisations and funders to guide funding of shoulder research for the next 5-10 years on topics that are important to patients, their carers and clinicians. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

PCA3 Reference Set Application: T2-Erg-Martin Sanda-Emory (2014) — EDRN Public Portal

Science.gov (United States)

We hypothesize that combining T2:erg (T2:erg) fusion and PCA3 detection in urine collected after digital rectal exam can improve the specificity of identifying clinically significant prostate cancer presence over the standard PSA and DRE. To address this hypothesis we propose to validate the performance of the urinary T2:erg in a multiplex model predicting the diagnosis of clinically significant prostate cancer on subsequent prostate biopsy using post-DRE pre biopsy urine specimens from a cohort of 900 men on the EDRN’s PCA3 trial.

ERG Protein Expression in Diagnostic Specimens Is Associated with Increased Risk of Progression During Active Surveillance for Prostate Cancer

DEFF Research Database (Denmark)

Berg, Kasper Drimer; Vainer, Ben; Thomsen, Frederik Birkebæk

2014-01-01

with a ready-to-use kit (anti-ERG, EPR3864). Men were characterised as ERG positive if a minimum of one tumour focus demonstrated ERG expression. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Overall AS progression was defined as clinical progression: increased clinical tumour category ≥cT2b by digital rectal...

Effects of Tannic Acid, Green Tea and Red Wine on hERG Channels Expressed in HEK293 Cells.

Directory of Open Access Journals (Sweden)

Xi Chu

Full Text Available Tannic acid presents in varying concentrations in plant foods, and in relatively high concentrations in green teas and red wines. Human ether-à-go-go-related gene (hERG channels expressed in multiple tissues (e.g. heart, neurons, smooth muscle and cancer cells, and play important roles in modulating cardiac action potential repolarization and tumor cell biology. The present study investigated the effects of tannic acid, green teas and red wines on hERG currents. The effects of tannic acid, teas and red wines on hERG currents stably transfected in HEK293 cells were studied with a perforated patch clamp technique. In this study, we demonstrated that tannic acid inhibited hERG currents with an IC50 of 3.4 μM and ~100% inhibition at higher concentrations, and significantly shifted the voltage dependent activation to more positive potentials (Δ23.2 mV. Remarkably, a 100-fold dilution of multiple types of tea (green tea, oolong tea and black tea or red wine inhibited hERG currents by ~90%, and significantly shifted the voltage dependent activation to more positive potentials (Δ30.8 mV and Δ26.0 mV, respectively. Green tea Lung Ching and red wine inhibited hERG currents, with IC50 of 0.04% and 0.19%, respectively. The effects of tannic acid, teas and red wine on hERG currents were irreversible. These results suggest tannic acid is a novel hERG channel blocker and consequently provide a new mechanistic evidence for understanding the effects of tannic acid. They also revealed the potential pharmacological basis of tea- and red wine-induced biology activities.

Effects of Tannic Acid, Green Tea and Red Wine on hERG Channels Expressed in HEK293 Cells

Science.gov (United States)

Xu, Bingyuan; Li, Wenya; Lin, Yue; Sun, Xiaorun; Ding, Chunhua; Zhang, Xuan

2015-01-01

Tannic acid presents in varying concentrations in plant foods, and in relatively high concentrations in green teas and red wines. Human ether-à-go-go-related gene (hERG) channels expressed in multiple tissues (e.g. heart, neurons, smooth muscle and cancer cells), and play important roles in modulating cardiac action potential repolarization and tumor cell biology. The present study investigated the effects of tannic acid, green teas and red wines on hERG currents. The effects of tannic acid, teas and red wines on hERG currents stably transfected in HEK293 cells were studied with a perforated patch clamp technique. In this study, we demonstrated that tannic acid inhibited hERG currents with an IC50 of 3.4 μM and ~100% inhibition at higher concentrations, and significantly shifted the voltage dependent activation to more positive potentials (Δ23.2 mV). Remarkably, a 100-fold dilution of multiple types of tea (green tea, oolong tea and black tea) or red wine inhibited hERG currents by ~90%, and significantly shifted the voltage dependent activation to more positive potentials (Δ30.8 mV and Δ26.0 mV, respectively). Green tea Lung Ching and red wine inhibited hERG currents, with IC50 of 0.04% and 0.19%, respectively. The effects of tannic acid, teas and red wine on hERG currents were irreversible. These results suggest tannic acid is a novel hERG channel blocker and consequently provide a new mechanistic evidence for understanding the effects of tannic acid. They also revealed the potential pharmacological basis of tea- and red wine-induced biology activities. PMID:26625122

Assessing the Contribution of the Oscillatory Potentials to the Genesis of the Photopic ERG with the Discrete Wavelet Transform.

Science.gov (United States)

Gauvin, Mathieu; Dorfman, Allison L; Trang, Nataly; Gauthier, Mercedes; Little, John M; Lina, Jean-Marc; Lachapelle, Pierre

2016-01-01

The electroretinogram (ERG) is composed of slow (i.e., a-, b-waves) and fast (i.e., oscillatory potentials: OPs) components. OPs have been shown to be preferably affected in some diseases (such as diabetic retinopathy), while the a- and b-waves remain relatively intact. The purpose of this study was to determine the contribution of OPs to the building of the ERG and to examine whether a signal mostly composed of OPs could also exist. DWT analyses were performed on photopic ERGs (flash intensities: -2.23 to 2.64 log cd·s·m -2 in 21 steps) obtained from normal subjects ( n = 40) and patients ( n = 21) affected with a retinopathy. In controls, the %OP value (i.e., OPs energy/ERG energy) is stimulus- and amplitude-independent (range: 56.6-61.6%; CV = 6.3%). In contrast, the %OPs measured from the ERGs of our patients varied significantly more (range: 35.4%-89.2%; p pathology, some presenting with ERGs that are almost solely composed of OPs. In conclusion, patients may present with a wide range of %OP values. Findings herein also support the hypothesis that, in certain conditions, the photopic ERG can be mostly composed of high-frequency components.

Assessing the Contribution of the Oscillatory Potentials to the Genesis of the Photopic ERG with the Discrete Wavelet Transform

Directory of Open Access Journals (Sweden)

Mathieu Gauvin

2016-01-01

Full Text Available The electroretinogram (ERG is composed of slow (i.e., a-, b-waves and fast (i.e., oscillatory potentials: OPs components. OPs have been shown to be preferably affected in some diseases (such as diabetic retinopathy, while the a- and b-waves remain relatively intact. The purpose of this study was to determine the contribution of OPs to the building of the ERG and to examine whether a signal mostly composed of OPs could also exist. DWT analyses were performed on photopic ERGs (flash intensities: −2.23 to 2.64 log cd·s·m−2 in 21 steps obtained from normal subjects (n=40 and patients (n=21 affected with a retinopathy. In controls, the %OP value (i.e., OPs energy/ERG energy is stimulus- and amplitude-independent (range: 56.6–61.6%; CV = 6.3%. In contrast, the %OPs measured from the ERGs of our patients varied significantly more (range: 35.4%–89.2%; p<0.05 depending on the pathology, some presenting with ERGs that are almost solely composed of OPs. In conclusion, patients may present with a wide range of %OP values. Findings herein also support the hypothesis that, in certain conditions, the photopic ERG can be mostly composed of high-frequency components.

An angular selective electron gun for the KATRIN experiment

Energy Technology Data Exchange (ETDEWEB)

Zacher, Michael; Ortjohann, Hans-Werner; Steinbrink, Nicholas; Josten, Lorenz; Hannen, Volker; Weinheimer, Christian; Winzen, Daniel [Westfaelische Wilhelms-Universitaet, Muenster (Germany); Collaboration: KATRIN-Collaboration

2013-07-01

The KArlsruhe TRItium Neutrino experiment aims for a measurement of the electron anti-neutrino mass with a sensitivity of 200 meV/c{sup 2} (95% C.L.) by analysing the endpoint region of the tritium β-decay. The main spectrometer (MAC-E filter type, 23m length) is one of the central parts of the experiment, featuring an energy resolution of Δ E<1 eV. For commissioning of the spectrometer a well defined electron source is needed that allows to determine the transmission characteristics and compare the electromagnetic properties to simulations. For this purpose an angular selective electron gun was developed. A pulsed UV-Laser produces electrons via the photo-electric effect, which are then accelerated electrostatically in a magnetic field. It features a small energy spread, a sharp selectable emission angle and covers the whole magnetic flux tube of KATRIN. By that, the characteristics of the spectrometer can be investigated with high precision. The time structure of the electron pulses allows time of flight measurements, offering enhanced sensitivity. The talk gives an overview about the e-gun design and its properties.

Calibration of the precision high voltage dividers of the KATRIN experiment

Energy Technology Data Exchange (ETDEWEB)

Rest, Oliver [Institut fuer Kernphysik, Westfaelische Wilhelms-Universitaet Muenster (Germany); Collaboration: KATRIN-Collaboration

2016-07-01

The KATRIN (KArlsruhe TRItium Neutrino) experiment will measure the endpoint region of the tritium β decay spectrum to determine the neutrino mass with a sensitivity of 200 meV/c{sup 2}. To achieve this sub-eV sensitivity the energy of the decay electrons will be analyzed using a MAC-E type spectrometer. The retarding potential of the MAC-E-filter (up to -35 kV) has to be monitored with a relative precision of 3 . 10{sup -6}. For this purpose the potential will be measured directly via two custom made precision high voltage dividers, which were developed and constructed in cooperation with the Physikalisch-Technische Bundesanstalt Braunschweig. In order to determine the absolute values and the stability of the scale factors of the voltage dividers, regular calibration measurements are essential. Such measurements have been performed during the last years using several different methods. The poster gives an overview of the methods and results of the calibration of the precision high voltage dividers.

Clonal Evaluation of Prostate Cancer by ERG/SPINK1 Status to Improve Prognosis Prediction

Science.gov (United States)

2017-12-01

19 NIH Exploiting drivers of androgen receptor signaling negative prostate cancer for precision medicine Goal(s): Identify novel potential drivers...AWARD NUMBER: W81XWH-14-1-0466 TITLE: Clonal evaluation of prostate cancer by ERG/SPINK1 status to improve prognosis prediction PRINCIPAL...Sept 2017 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Clonal Evaluation of Prostate Cancer by ERG/SPINK1 Status to Improve Prognosis Prediction 5b

Interaction between the cardiac rapidly (IKr) and slowly (IKs) activating delayed rectifier potassium channels revealed by low K+-induced hERG endocytic degradation.

Science.gov (United States)

Guo, Jun; Wang, Tingzhong; Yang, Tonghua; Xu, Jianmin; Li, Wentao; Fridman, Michael D; Fisher, John T; Zhang, Shetuan

2011-10-07

Cardiac repolarization is controlled by the rapidly (I(Kr)) and slowly (I(Ks)) activating delayed rectifier potassium channels. The human ether-a-go-go-related gene (hERG) encodes I(Kr), whereas KCNQ1 and KCNE1 together encode I(Ks). Decreases in I(Kr) or I(Ks) cause long QT syndrome (LQTS), a cardiac disorder with a high risk of sudden death. A reduction in extracellular K(+) concentration ([K(+)](o)) induces LQTS and selectively causes endocytic degradation of mature hERG channels from the plasma membrane. In the present study, we investigated whether I(Ks) compensates for the reduced I(Kr) under low K(+) conditions. Our data show that when hERG and KCNQ1 were expressed separately in human embryonic kidney (HEK) cells, exposure to 0 mM K(+) for 6 h completely eliminated the mature hERG channel expression but had no effect on KCNQ1. When hERG and KCNQ1 were co-expressed, KCNQ1 significantly delayed 0 mM K(+)-induced hERG reduction. Also, hERG degradation led to a significant reduction in KCNQ1 in 0 mM K(+) conditions. An interaction between hERG and KCNQ1 was identified in hERG+KCNQ1-expressing HEK cells. Furthermore, KCNQ1 preferentially co-immunoprecipitated with mature hERG channels that are localized in the plasma membrane. Biophysical and pharmacological analyses indicate that although hERG and KCNQ1 closely interact with each other, they form distinct hERG and KCNQ1 channels. These data extend our understanding of delayed rectifier potassium channel trafficking and regulation, as well as the pathology of LQTS.

TMPRSS2-ERG -specific transcriptional modulation is associated with prostate cancer biomarkers and TGF-β signaling

International Nuclear Information System (INIS)

Brase, Jan C; Sirma, Hüseyin; Sauter, Guido; Simon, Ronald; Schlomm, Thorsten; Beißbarth, Tim; Korf, Ulrike; Kuner, Ruprecht; Sültmann, Holger; Johannes, Marc; Mannsperger, Heiko; Fälth, Maria; Metzger, Jennifer; Kacprzyk, Lukasz A; Andrasiuk, Tatjana; Gade, Stephan; Meister, Michael

2011-01-01

TMPRSS2-ERG gene fusions occur in about 50% of all prostate cancer cases and represent promising markers for molecular subtyping. Although TMPRSS2-ERG fusion seems to be a critical event in prostate cancer, the precise functional role in cancer development and progression is still unclear. We studied large-scale gene expression profiles in 47 prostate tumor tissue samples and in 48 normal prostate tissue samples taken from the non-suspect area of clinical low-risk tumors using Affymetrix GeneChip Exon 1.0 ST microarrays. Comparison of gene expression levels among TMPRSS2-ERG fusion-positive and negative tumors as well as benign samples demonstrated a distinct transcriptional program induced by the gene fusion event. Well-known biomarkers for prostate cancer detection like CRISP3 were found to be associated with the gene fusion status. WNT and TGF-β/BMP signaling pathways were significantly associated with genes upregulated in TMPRSS2-ERG fusion-positive tumors. The TMPRSS2-ERG gene fusion results in the modulation of transcriptional patterns and cellular pathways with potential consequences for prostate cancer progression. Well-known biomarkers for prostate cancer detection were found to be associated with the gene fusion. Our results suggest that the fusion status should be considered in retrospective and future studies to assess biomarkers for prostate cancer detection, progression and targeted therapy

Targeting TMPRSS2-ERG in Prostate Cancer

Science.gov (United States)

2017-11-01

AWARD NUMBER: W81XWH-13-1-0212 TITLE: Targeting TMPRSS2-ERG in Prostate Cancer PRINCIPAL INVESTIGATOR: David Takeda CONTRACTING...ORGANIZATION: Dana-Farber Cancer Institute Boston, MA 02215 REPORT DATE: November 2017 TYPE OF REPORT: Final PREPARED FOR: U.S. Army Medical Research...Prostate Cancer 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-13-1-0212 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) David Takeda 5d. PROJECT NUMBER 5e

Exclusion of aldose reductase as a mediator of ERG deficits in a mouse model of diabetic eye disease.

Science.gov (United States)

Samuels, Ivy S; Lee, Chieh-Allen; Petrash, J Mark; Peachey, Neal S; Kern, Timothy S

2012-11-01

Streptozotocin (STZ)-induced diabetes is associated with reductions in the electrical response of the outer retina and retinal pigment epithelium (RPE) to light. Aldose reductase (AR) is the first enzyme required in the polyol-mediated metabolism of glucose, and AR inhibitors have been shown to improve diabetes-induced electroretinogram (ERG) defects. Here, we used control and AR -/- mice to determine if genetic inactivation of this enzyme likewise inhibits retinal electrophysiological defects observed in a mouse model of type 1 diabetes. STZ was used to induce hyperglycemia and type 1 diabetes. Diabetic and age-matched nondiabetic controls of each genotype were maintained for 22 weeks, after which ERGs were used to measure the light-evoked components of the RPE (dc-ERG) and the neural retina (a-wave, b-wave). In comparison to their nondiabetic controls, wildtype (WT) and AR -/- diabetic mice displayed significant decreases in the c-wave, fast oscillation, and off response components of the dc-ERG but not in the light peak response. Nondiabetic AR -/- mice displayed larger ERG component amplitudes than did nondiabetic WT mice; however, the amplitude of dc-ERG components in diabetic AR -/- animals were similar to WT diabetics. ERG a-wave amplitudes were not reduced in either diabetic group, but b-wave amplitudes were lower in WT and AR -/-diabetic mice. These findings demonstrate that the light-induced responses of the RPE and outer retina are disrupted in diabetic mice, but these defects are not due to photoreceptor dysfunction, nor are they ameliorated by deletion of AR. This latter finding suggests that benefits observed in other studies utilizing pharmacological inhibitors of AR might have been secondary to off-target effects of the drugs.

Loss of the NKX3.1 tumorsuppressor promotes the TMPRSS2-ERG fusion gene expression in prostate cancer

International Nuclear Information System (INIS)

Thangapazham, Rajesh; Saenz, Francisco; Katta, Shilpa; Mohamed, Ahmed A; Tan, Shyh-Han; Petrovics, Gyorgy; Srivastava, Shiv; Dobi, Albert

2014-01-01

In normal prostate epithelium the TMPRSS2 gene encoding a type II serine protease is directly regulated by male hormones through the androgen receptor. In prostate cancer ERG protooncogene frequently gains hormonal control by seizing gene regulatory elements of TMPRSS2 through genomic fusion events. Although, the androgenic activation of TMPRSS2 gene has been established, little is known about other elements that may interact with TMPRSS2 promoter sequences to modulate ERG expression in TMPRSS2-ERG gene fusion context. Comparative genomic analyses of the TMPRSS2 promoter upstream sequences and pathway analyses were performed by the Genomatix Software. NKX3.1 and ERG genes expressions were evaluated by immunoblot or by quantitative Real-Time PCR (qRT-PCR) assays in response to siRNA knockdown or heterologous expression. QRT-PCR assay was used for monitoring the gene expression levels of NKX3.1-regulated genes. Transcriptional regulatory function of NKX3.1 was assessed by luciferase assay. Recruitment of NKX3.1 to its cognate elements was monitored by Chromatin Immunoprecipitation assay. Comparative analysis of the TMPRSS2 promoter upstream sequences among different species revealed the conservation of binding sites for the androgen inducible NKX3.1 tumor suppressor. Defects of NKX3.1, such as, allelic loss, haploinsufficiency, attenuated expression or decreased protein stability represent established pathways in prostate tumorigenesis. We found that NKX3.1 directly binds to TMPRSS2 upstream sequences and negatively regulates the expression of the ERG protooncogene through the TMPRSS2-ERG gene fusion. These observations imply that the frequently noted loss-of-function of NKX3.1 cooperates with the activation of TMPRSS2-ERG fusions in prostate tumorigenesis

Web 2.0 Dienste als Ergänzung zu algorithmischen Suchmaschinen

CERN Document Server

Deutschland. Bundesministerium für Wirtschaft und Technologie; Maas, Christian

2008-01-01

Dokumentiert die Ergebnisse des Fachprojekts "Einbingung von Frage-Antwort-Diensten in die Web-Suche", Wintersemester 2007/2008, Dept. Information, Hochschule für angewandte Wissenschaften Hamburg. Mit sozialen Suchdiensten - wie z.B. Yahoo Clever, Lycos iQ oder Mister Wong - ist eine Ergänzung zu den bisherigen Ansätzen in der Web-Suche entstanden. Während Google und Co. automatisch generierte Trefferlisten bieten, binden soziale Suchdienste die Anwender zur Generierung der Suchergebnisse in den Suchprozess ein. Vor diesem Hintergrund wird in diesem Buch der Frage nachgegangen, inwieweit soziale Suchdienste mit traditionellen Suchmaschinen konkurrieren oder diese qualitativ ergänzen können. Der vorliegende Band beleuchtet die hier aufgeworfene Fragestellung aus verschiedenen Perspektiven, um auf die Bedeutung von sozialen Suchdiensten zu schließen.

Background reduction of the KATRIN spectrometers. Transmission function of the pre-spectrometer and systematic tests of the main-spectrometer wire electrode

Energy Technology Data Exchange (ETDEWEB)

Prall, Matthias

2011-07-04

The KArlsruhe TRItium Neutrino experiment, KATRIN will determine the mass of the anti {nu}{sub e} with a sensitivity of 0.2 eV (90% C.L.) via a measurement of the {beta}-spectrum of tritium decaying in a windowless gaseous molecular tritium source near its endpoint of 18.57 keV. This approach relies exclusively on the relativistic kinematics of the decay products rendering the experiment model independent and reducing the systematic uncertainty. An ultra-low background of a few mHz and an energy resolution of 0.93 eV are among the requirements to reach the sensitivity. These demands are fulfilled with the main spectrometer (MS). While the {beta}-decay electrons are guided by a magnetic field through the experiment, the MS acts as a high-pass filter for the {beta}-decay electrons. Only those above an energy barrier, the retarding potential, are transmitted to the detector. The last about 30 eV of the T{sub 2} {beta}-spectrum will be scanned in this way. The MS is equipped with a 650 m{sup 2}, two-layered, UHV compatible and quasi-massless wire electrode suppressing secondary electron background originating at the main-spectrometer walls and caused by residual radioactivity and cosmic muons. Its energy resolution of 0.93 eV is only achieved, if a large part of the 248 wire electrode modules, which determine the electric field inside the MS, has a mechanical precision of 0.2 mm. Not a single of the about 28.000 wires of the electrode must break during the lifetime of KATRIN. A 2-dimensional laser sensor for contact-less position (precision about 0.01 mm) and tension (precision about 0.04 N) measurements was developed and applied, to firstly, verify the mechanical precision of the electrode modules and secondly, to examine their reliability. A 3-dimensional coordinate measurement table was automated to perform these measurements in a clean room. This table was also used to verify the precision of components using a camera system and image recognition methods (0.05 mm

Katrin Schütz: Geschlechterentwürfe im literarischen Werk von Lou Andreas-Salomé unter Berücksichtigung ihrer Geschlechtertheorie. Würzburg: Verlag Königshausen & Neumann 2008

Directory of Open Access Journals (Sweden)

Romana Weiershausen

2009-03-01

Full Text Available Katrin Schütz hat eine Studie zu Geschlechterkonzeptionen in Lou Andreas-Salomés Frühwerk vorgelegt, in der auch die bislang wenig berücksichtigten literarischen Texte der Autorin ausgewertet werden. Die Anlage zielt auf eine Überblicksdarstellung, hinter der die differenzierende Reflexion der einzelnen Thesen zurück steht: Schütz geht es um die Konturierung einer Typologie. Durch die erweiterte Textgrundlage wird dabei Neues erschlossen, woraus sich anregende Impulse für die Jahrhundertwende-Forschung ergeben.Katrin Schütz’s study of gender conceptions in Lou Andreas-Salomé’s early work considers those literary texts often ignored by scholarship. The study is constructed as an overview, in light of which a differentiated reflection on the individual theses falls short: Schütz intends to formulate a typology. The expanded textual basis allows for the creation of something new, which will in turn provide inspirational impulses for turn-of-the-century research.

Thermal behavior and ice-table depth within the north polar erg of Mars

Science.gov (United States)

Putzig, Nathaniel E.; Mellon, Michael T.; Herkenhoff, Kenneth E.; Phillips, Roger J.; Davis, Brian J.; Ewer, Kenneth J.; Bowers, Lauren M.

2014-02-01

We fully resolve a long-standing thermal discrepancy concerning the north polar erg of Mars. Several recent studies have shown that the erg's thermal properties are consistent with normal basaltic sand overlying shallow ground ice or ice-cemented sand. Our findings bolster that conclusion by thoroughly characterizing the thermal behavior of the erg, demonstrating that other likely forms of physical heterogeneity play only a minor role, and obviating the need to invoke exotic materials. Thermal inertia as calculated from orbital temperature observations of the dunes has previously been found to be more consistent with dust-sized materials than with sand. Since theory and laboratory data show that dunes will only form out of sand-sized particles, exotic sand-sized agglomerations of dust have been invoked to explain the low values of thermal inertia. However, the polar dunes exhibit the same darker appearance and color as that of dunes found elsewhere on the planet that have thermal inertia consistent with normal sand-sized basaltic grains, whereas Martian dust deposits are generally lighter and redder. The alternative explanation for the discrepancy as a thermal effect of a shallow ice table is supported by our analysis of observations from the Mars Global Surveyor Thermal Emission Spectrometer and the Mars Odyssey Thermal Emission Imaging System and by forward modeling of physical heterogeneity. In addition, our results exclude a uniform composition of dark dust-sized materials, and they show that the thermal effects of the dune slopes and bright interdune materials evident in high-resolution images cannot account for the erg's thermal behavior.

Prognostic Significance of TMPRSS2-ERG Fusion Gene in Prostate Cancer

Czech Academy of Sciences Publication Activity Database

Kulda, V.; Topolčan, O.; Kučera, R.; Kripnerová, M.; Srbecká, K.; Hora, M.; Hes, O.; Klečka, J.; Babuška, V.; Rousárová, M.; Benson, Veronika; Pesta, M.

2016-01-01

Roč. 36, č. 7 (2016), s. 4787-4793 ISSN 0250-7005 Institutional support: RVO:61388971 Keywords : Prostate cancer * TMPRSS2-ERG * PSA Subject RIV: FD - Oncology ; Hematology Impact factor: 1.937, year: 2016

Improved functional expression of recombinant human ether-a-go-go (hERG K+ channels by cultivation at reduced temperature

Directory of Open Access Journals (Sweden)

Hamilton Bruce

2007-12-01

Full Text Available Abstract Background HERG potassium channel blockade is the major cause for drug-induced long QT syndrome, which sometimes cause cardiac disrhythmias and sudden death. There is a strong interest in the pharmaceutical industry to develop high quality medium to high-throughput assays for detecting compounds with potential cardiac liability at the earliest stages of drug development. Cultivation of cells at lower temperature has been used to improve the folding and membrane localization of trafficking defective hERG mutant proteins. The objective of this study was to investigate the effect of lower temperature maintenance on wild type hERG expression and assay performance. Results Wild type hERG was stably expressed in CHO-K1 cells, with the majority of channel protein being located in the cytoplasm, but relatively little on the cell surface. Expression at both locations was increased several-fold by cultivation at lower growth temperatures. Intracellular hERG protein levels were highest at 27°C and this correlated with maximal 3H-dofetilide binding activity. In contrast, the expression of functionally active cell surface-associated hERG measured by patch clamp electrophysiology was optimal at 30°C. The majority of the cytoplasmic hERG protein was associated with the membranes of cytoplasmic vesicles, which markedly increased in quantity and size at lower temperatures or in the presence of the Ca2+-ATPase inhibitor, thapsigargin. Incubation with the endocytic trafficking blocker, nocodazole, led to an increase in hERG activity at 37°C, but not at 30°C. Conclusion Our results are consistent with the concept that maintenance of cells at reduced temperature can be used to boost the functional expression of difficult-to-express membrane proteins and improve the quality of assays for medium to high-throughput compound screening. In addition, these results shed some light on the trafficking of hERG protein under these growth conditions.

Status of the cryogenic pumping section of the KATRIN experiment

Energy Technology Data Exchange (ETDEWEB)

Roettele, Carsten [Karlsruhe Institute of Technology (KIT) (Germany). Institut fuer Kernphysik (IKP); Collaboration: KATRIN-Collaboration

2016-07-01

The Karlsruhe Tritium Neutrino (KATRIN) experiment uses the kinematics of tritium β-decay to determine the electron antineutrino mass with a sensitivity of m{sub ν}=200 meV/c{sup 2} (90 % C.L.). In order to measure the decay electrons it is important to guide them adiabatically from the source to the spectrometer. In addition the diffusion of tritium into the spectrometers from the source has to be reduced by 14 magnitudes of order as tritium inside the spectrometers would induce additional background. For these two tasks the transport and pumping section were constructed. The last part of this section is the Cryogenic Pumping Section (CPS), which aims to reduce the residual gas flow by not less than seven orders of magnitude. For this a 3 K cold argon frost area (surface ∼ 2 m{sup 2}) will be prepared to adsorb the incoming tritium molecules. This talk will present the milestones which were reached since the CPS arrived on 30th July 2015 on KIT. Amongst others the calculations of the magnetic flux tube through the CPS based on as-built measurements of the coil geometries are presented.

Upper shelf toughness of six submerged-arc weldmetals manufactured using Linde 124 flux

International Nuclear Information System (INIS)

Druce, S.G.; Hippsley, C.A.

1984-06-01

This paper describes the testing technique, data analysis procedures and results from the first phase of an experimental programme investigating upper shelf toughness of six submerged-arc weldmetals. The welds were manufactured using uncoated, Nickel coated and Copper coated wire electrodes and Linde 124 flux. J integral crack growth resistance curves have been derived from tests on single specimens over a range in temperature from 150 to 290 deg C. The results indicate a general decline in toughness with increasing temperature. At 290 deg C, the levels of initiation toughness from all six welds were essentially constant varying between 152 to 159 MPa square root of m. The Jsub(I)-R curves derived from this work are compared with toughness data used in the Marshall Study Group report of an assessment of the integrity of PWR pressure vessels. (author)

On- and off-response ERGs elicited by sawtooth stimuli in normal subjects and glaucoma patients.

Science.gov (United States)

Pangeni, Gobinda; Lämmer, Robert; Tornow, Ralf P; Horn, Folkert K; Kremers, Jan

2012-06-01

The aim of this study is to measure the on- and off-responses and their response asymmetries elicited by sawtooth stimuli in normal subjects and glaucoma patients. Furthermore, the correlation between the ERGs and other functional and structural parameters are investigated. Full-field stimuli were produced using a Ganzfeld bowl with Light Emitting Diodes (LEDs) as light sources. On- and off-response ERGs were recorded from 17 healthy subjects, 12 pre-perimetric and 15 perimetric glaucoma patients using 4-Hz luminance rapid-on and rapid-off sawtooth stimuli (white light; mean luminance 55 cd/m(2)) at 100% contrast. The on- and off-responses were added to study response asymmetries. In addition, flash ERGs were elicited by red stimuli (200 cd/m(2)) on a blue background (10 cd/m(2)). The mean deviations (MD) of the visual field defects were obtained by standard automated perimetry. The retinal nerve fibre layer thickness (RNFLT) was measured with Spectral Domain Optical Coherence Tomography (SOCT). We studied the correlation between ERG response amplitudes, visual field mean deviation (MDs) and RNFLT values. The on-responses showed an initial negative (N-on) followed by a positive (P-on), a late positive (LP-on) and a late negative responses (LN-on). The off-responses showed an initial positive (P-off) a late positive (LP-off) and a late negative response (LN-off). The addition of on- and off-responses revealed an initial positive (P-add) and a late negative response (LN-add). The on-response components (N-on, P-on and LN-on) in the glaucoma patients were relatively similar to those of the control subjects. However, the LP-on was significantly elevated (p = 0.03) in perimetric patients. The LP-off was significantly elevated (p < 0.001), and the amplitude of LN-off was significantly reduced in perimetric patients (p = 0.02). The LN-add amplitude was significantly reduced (p < 0.001) and delayed (p = 0.03) in perimetric patients. The amplitudes of the LN-off and LN

Heterogeneity of PTEN and ERG expression in prostate cancer on core needle biopsies: implications for cancer risk stratification and biomarker sampling.

Science.gov (United States)

Shah, Rajal B; Bentley, James; Jeffery, Zach; DeMarzo, Angelo M

2015-05-01

ERG and PTEN biomarkers are increasingly being analyzed on prostate core biopsies (NBXs); ERG as a marker of clonality and number of separately arising tumor foci and PTEN for prognostic information. Yet, in patients with multiple biopsy cores positive for cancer (PCa), there is no standardized approach for interrogation of these biomarkers in terms of the number of positive cores to evaluate. A total of 194 NBX cases containing more than one positive core with cancer were evaluated for ERG overexpression and PTEN loss by immunostaining (immunohistochemistry) of all positive cores. ERG overexpression or PTEN loss in at least one cancer core was present in 111 (57%) and 69 (36%) cases respectively. ERG overexpression was significantly associated with PTEN loss (P < .0001), and PTEN loss was associated with a high Gleason score (P < .0001). Inter- and intra-tumor core staining heterogeneity for ERG overexpression occurred in 42% and 5% cases and for PTEN loss both intra- and inter-tumor core heterogeneity was 68%. PTEN staining was highly discordant between PCa sites regardless of laterality. When the Gleason score was non-uniform across PCa sites, the combination of cores showing the highest Gleason score and largest tumor volume provided the best representation of ERG overexpression (92%) and PTEN loss (98%). When grades were uniform across cancer sites, the highest tumor volume core was generally representative of ERG overexpression (90%) but was less representative for PTEN loss (76%). Our results suggest that knowledge of this heterogeneity is critical for developing optimal yet cost-effective strategies to identify these underlying molecular abnormalities. Copyright © 2015 Elsevier Inc. All rights reserved.

On the construction of QED using ERG

International Nuclear Information System (INIS)

Sonoda, H

2007-01-01

It has been known for some time that a smooth momentum cutoff is compatible with local gauge symmetries. In this paper, we show concretely how to construct QED using the exact renormalization group (ERG). First, we give a new derivation of the Ward identity for the Wilson action using the technique of composite operators. Second, parametrizing the theory by its asymptotic behaviour for a large cutoff, we show how to fine tune the parameters to satisfy the identity. Third, we recast the identity as an invariance of the Wilson action under a nonlinear BRST transformation

Rehabilitating drug-induced long-QT promoters: in-silico design of hERG-neutral cisapride analogues with retained pharmacological activity.

Science.gov (United States)

Durdagi, Serdar; Randall, Trevor; Duff, Henry J; Chamberlin, Adam; Noskov, Sergei Y

2014-03-08

The human ether-a-go-go related gene 1 (hERG1), which codes for a potassium ion channel, is a key element in the cardiac delayed rectified potassium current, IKr, and plays an important role in the normal repolarization of the heart's action potential. Many approved drugs have been withdrawn from the market due to their prolongation of the QT interval. Most of these drugs have high potencies for their principal targets and are often irreplaceable, thus "rehabilitation" studies for decreasing their high hERG1 blocking affinities, while keeping them active at the binding sites of their targets, have been proposed to enable these drugs to re-enter the market. In this proof-of-principle study, we focus on cisapride, a gastroprokinetic agent withdrawn from the market due to its high hERG1 blocking affinity. Here we tested an a priori strategy to predict a compound's cardiotoxicity using de novo drug design with molecular docking and Molecular Dynamics (MD) simulations to generate a strategy for the rehabilitation of cisapride. We focused on two key receptors, a target interaction with the (adenosine) receptor and an off-target interaction with hERG1 channels. An analysis of the fragment interactions of cisapride at human A2A adenosine receptors and hERG1 central cavities helped us to identify the key chemical groups responsible for the drug activity and hERG1 blockade. A set of cisapride derivatives with reduced cardiotoxicity was then proposed using an in-silico two-tier approach. This set was compared against a large dataset of commercially available cisapride analogs and derivatives. An interaction decomposition of cisapride and cisapride derivatives allowed for the identification of key active scaffolds and functional groups that may be responsible for the unwanted blockade of hERG1.

Bag1 Co-chaperone Promotes TRC8 E3 Ligase-dependent Degradation of Misfolded Human Ether a Go-Go-related Gene (hERG) Potassium Channels.

Science.gov (United States)

Hantouche, Christine; Williamson, Brittany; Valinsky, William C; Solomon, Joshua; Shrier, Alvin; Young, Jason C

2017-02-10

Cardiac long QT syndrome type 2 is caused by mutations in the human ether a go-go-related gene (hERG) potassium channel, many of which cause misfolding and degradation at the endoplasmic reticulum instead of normal trafficking to the cell surface. The Hsc70/Hsp70 chaperones assist the folding of the hERG cytosolic domains. Here, we demonstrate that the Hsp70 nucleotide exchange factor Bag1 promotes hERG degradation by the ubiquitin-proteasome system at the endoplasmic reticulum to regulate hERG levels and channel activity. Dissociation of hERG complexes containing Hsp70 and the E3 ubiquitin ligase CHIP requires the interaction of Bag1 with Hsp70, but this does not involve the Bag1 ubiquitin-like domain. The interaction with Bag1 then shifts hERG degradation to the membrane-anchored E3 ligase TRC8 and its E2-conjugating enzyme Ube2g2, as determined by siRNA screening. TRC8 interacts through the transmembrane region with hERG and decreases hERG functional expression. TRC8 also mediates degradation of the misfolded hERG-G601S disease mutant, but pharmacological stabilization of the mutant structure prevents degradation. Our results identify TRC8 as a previously unknown Hsp70-independent quality control E3 ligase for hERG. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Electron spectroscopy measurements with a shifted analyzing plane setting in the KATRIN main spectrometer

Energy Technology Data Exchange (ETDEWEB)

Dyba, Stephan [Institut fuer Kernphysik, Uni Muenster (Germany); Collaboration: KATRIN-Collaboration

2016-07-01

With the KATRIN (KArlsruhe TRItium Neutrino) experiment the endpoint region of the tritium beta decay will be measured to determine the electron-neutrino mass with a sensitivity of 200 meV/c{sup 2} (90% C.L.). For the high precision which is needed to achieve the sub-eV range a MAC-E filter type spectrometer is used to analyze the electron energy. To understand the various background contributions inside the spectrometer vessel different electric and magnetic field settings were investigated during the last commissioning phase. This talk will focus on the so called shifted analyzing plane measurement in which the field settings were tuned in a way to provide non standard potential barriers within the spectrometer. The different settings allowed to perform a spectroscopic measurement, determining the energy spectrum of background electrons born within the spectrometer.

The Role of mf-ERG in the Diagnosis and Treatment of Age-Related Macular Degeneration: Electrophysiological Features of AMD.

Science.gov (United States)

Moschos, Marilita M; Nitoda, Eirini

2018-01-01

Age-related macular cegeneration (AMD) is the leading cause of visual dysfunction worldwide, affecting 9-25% of individuals between 65 and 75 years old. We have reviewed the published articles investigating the role of multifocal electroretinogram (mf-ERG) in the diagnosis and treatment of AMD. Visual evoked potentials have revealed decreased amplitudes and higher latencies in patients with AMD, while the degeneration of photoreceptors and abnormalities of retinal pigment epithelium can be identified by electro-oculogram recordings. Moreover, ERG can detect the functional abnormalities observed in AMD and evaluate each therapeutic approach. The record of local electrophysiological responses coming from different retinal areas can be accurately performed by mfERG. The accuracy of mfERG in detecting the degeneration of photoreceptors, as well the disturbances of macular function, could be useful both in the early diagnosis of AMD and the assessment of treatment efficacy.

Application of Wave Distribution Function Method to the ERG/PWE Data

Science.gov (United States)

Ota, M.; Kasahara, Y.; Matsuda, S.; Kojima, H.; Matsuoka, A.; Hikishima, M.; Kasaba, Y.; Ozaki, M.; Yagitani, S.; Tsuchiya, F.; Kumamoto, A.

2017-12-01

The ERG (Arase) satellite was launched on 20 December 2016 to study acceleration and loss mechanisms of relativistic electrons in the Earth's magnetosphere. The Plasma Wave Experiment (PWE), which is one of the science instruments on board the ERG satellite, measures electric field and magnetic field. The PWE consists of three sub-systems; EFD (Electric Field Detector), OFA/WFC (Onboard Frequency Analyzer and Waveform Capture), and HFA (High Frequency Analyzer).The OFA/WFC measures electromagnetic field spectra and raw waveforms in the frequency range from few Hz to 20 kHz. The OFA produces three kind of data; OFA-SPEC (power spectrum), OFA-MATRIX (spectral matrix), and OFA-COMPLEX (complex spectrum). The OFA-MATRIX measures ensemble averaged complex cross-spectra of two electric field components, and of three magnetic field components. The OFA-COMPLEX measures instantaneous complex spectra of electric and magnetic fields. These data are produced every 8 seconds in the nominal mode, and it can be used for polarization analysis and wave propagation direction finding.In general, spectral matrix composed by cross-spectra of observed signals is used for direction finding, and many algorithms have been proposed. For example, Means method and SVD method can be applied on the assumption that the spectral matrix is consists of a single plane wave, while wave distribution function (WDF) method is applicable even to the data in which multiple numbers of plane waves are simultaneously included. In this presentation, we introduce the results when the WDF method is applied to the ERG/PWE data.

The effects of deoxyelephantopin on the cardiac delayed rectifier potassium channel current (IKr) and human ether-a-go-go-related gene (hERG) expression.

Science.gov (United States)

Teah, Yi Fan; Abduraman, Muhammad Asyraf; Amanah, Azimah; Adenan, Mohd Ilham; Sulaiman, Shaida Fariza; Tan, Mei Lan

2017-09-01

Elephantopus scaber Linn and its major bioactive component, deoxyelephantopin are known for their medicinal properties and are often reported to have various cytotoxic and antitumor activities. This plant is widely used as folk medicine for a plethora of indications although its safety profile remains unknown. Human ether-a-go-go-related gene (hERG) encodes the cardiac I Kr current which is a determinant of the duration of ventricular action potentials and QT interval. The hERG potassium channel is an important antitarget in cardiotoxicity evaluation. This study investigated the effects of deoxyelephantopin on the current, mRNA and protein expression of hERG channel in hERG-transfected HEK293 cells. The hERG tail currents following depolarization pulses were insignificantly affected by deoxyelephantopin in the transfected cell line. Current reduction was less than 40% as compared with baseline at the highest concentration of 50 μM. The results were consistent with the molecular docking simulation and hERG surface protein expression. Interestingly, it does not affect the hERG expression at both transcriptional and translational level at most concentrations, although higher concentration at 10 μM caused protein accumulation. In conclusion, deoxyelephantopin is unlikely a clinically significant hERG channel and I kr blocker. Copyright © 2017 Elsevier Ltd. All rights reserved.

hERG1 channels are overexpressed in glioblastoma multiforme and modulate VEGF secretion in glioblastoma cell lines

Science.gov (United States)

Masi, A; Becchetti, A; Restano-Cassulini, R; Polvani, S; Hofmann, G; Buccoliero, A M; Paglierani, M; Pollo, B; Taddei, G L; Gallina, P; Di Lorenzo, N; Franceschetti, S; Wanke, E; Arcangeli, A

2005-01-01

Recent studies have led to considerable advancement in our understanding of the molecular mechanisms that underlie the relentless cell growth and invasiveness of human gliomas. Partial understanding of these mechanisms has (1) improved the classification for gliomas, by identifying prognostic subgroups, and (2) pointed to novel potential therapeutic targets. Some classes of ion channels have turned out to be involved in the pathogenesis and malignancy of gliomas. We studied the expression and properties of K+ channels in primary cultures obtained from surgical specimens: human ether a gò-gò related (hERG)1 voltage-dependent K+ channels, which have been found to be overexpressed in various human cancers, and human ether a gò-gò-like 2 channels, that share many of hERG1's biophysical features. The expression pattern of these two channels was compared to that of the classical inward rectifying K+ channels, IRK, that are widely expressed in astrocytic cells and classically considered a marker of astrocytic differentiation. In our study, hERG1 was found to be specifically overexpressed in high-grade astrocytomas, that is, glioblastoma multiforme (GBM). In addition, we present evidence that, in GBM cell lines, hERG1 channel activity actively contributes to malignancy by promoting vascular endothelial growth factor secretion, thus stimulating the neoangiogenesis typical of high-grade gliomas. Our data provide important confirmation for studies proposing the hERG1 channel as a molecular marker of tumour progression and a possible target for novel anticancer therapies. PMID:16175187

Management and Beneficial Reuse of Overburden Material - Linde Formerly Utilized Sites Remedial Action Program (FUSRAP) Remediation Project

International Nuclear Information System (INIS)

Boyle, J.D.; Schwippert, M.; Lorenz, W.D.

2009-01-01

This paper outlines three separate and distinct situations where the proper management of overburden material allows for the beneficial reuse of overburden material. Beneficial reuse of overburden material at the Linde Project was made possible by a simultaneous combination of physical conditions at the site in conjunction with collaborative planning and cooperation between U.S. Army Corps of Engineers - Buffalo District, New York State Department of Energy and Conservation, the Owner and Shaw Environmental and Infrastructure. Efforts by the project team focused on maintaining compliance with project plan requirements, communicating the plan to all parties, executing the plan safely and efficiently, and emphasizing fiscal responsibility to ensure maximum cost savings. (authors)

ERG and GRG review of the draft of ''preliminary test plan for in situ testing from an exploratory shaft in salt - October 1983''

International Nuclear Information System (INIS)

Kalia, H.N.

1986-03-01

The Engineering Review Group (ERG) and Geologic Review Group (GRG) were established by the Office of Nuclear Waste Isolation (ONWI) to help evaluate engineering- and geologic-related issues in the US Department of Energy's nuclear waste repository program. The January 1984 meeting of the ERG and GRG reviewed the In Situ Test Plan (ISTP) titled ''Preliminary Test Plan for In Situ Testing From an Exploratory Shaft in Salt - October 1983.'' This report documents the ERG's and GRG's comments and recommendations on this subject and the ONWI responses to the specific points raised by the ERG and GRG. 6 refs., 2 figs., 1 tab

In Silico Predictions of hERG Channel Blockers in Drug Discovery

DEFF Research Database (Denmark)

Taboureau, Olivier; Sørensen, Flemming Steen

2011-01-01

The risk for cardiotoxic side effects represents a major problem in clinical studies of drug candidates and regulatory agencies have explicitly recommended that all new drug candidates should be tested for blockage of the human Ether-a-go-go Related-Gene (hERG) potassium channel. Indeed, several ...

Evaluation of ERG and SPINK1 by Immunohistochemical Staining and Clinicopathological Outcomes in a Multi-Institutional Radical Prostatectomy Cohort of 1067 Patients.

Directory of Open Access Journals (Sweden)

James D Brooks

Full Text Available Distinguishing between patients with early stage, screen detected prostate cancer who must be treated from those that can be safely watched has become a major issue in prostate cancer care. Identification of molecular subtypes of prostate cancer has opened the opportunity for testing whether biomarkers that characterize these subtypes can be used as biomarkers of prognosis. Two established molecular subtypes are identified by high expression of the ERG oncoprotein, due to structural DNA alterations that encode for fusion transcripts in approximately ½ of prostate cancers, and over-expression of SPINK1, which is purportedly found only in ERG-negative tumors. We used a multi-institutional prostate cancer tissue microarray constructed from radical prostatectomy samples with associated detailed clinical data and with rigorous selection of recurrent and non-recurrent cases to test the prognostic value of immunohistochemistry staining results for the ERG and SPINK1 proteins. In univariate analysis, ERG positive cases (419/1067; 39% were associated with lower patient age, pre-operative serum PSA levels, lower Gleason scores (≤ 3+4=7 and improved recurrence free survival (RFS. On multivariate analysis, ERG status was not correlated with RFS, disease specific survival (DSS or overall survival (OS. High-level SPINK1 protein expression (33/1067 cases; 3% was associated with improved RFS on univariate and multivariate Cox regression analysis. Over-expression of either protein was not associated with clinical outcome. While expression of ERG and SPINK1 proteins was inversely correlated, it was not mutually exclusive since 3 (0.28% cases showed high expression of both. While ERG and SPINK1 appear to identify discrete molecular subtypes of prostate cancer, only high expression of SPINK1 was associated with improved clinical outcome. However, by themselves, neither ERG nor SPINK1 appear to be useful biomarkers for prognostication of early stage prostate

Evaluation of ERG and SPINK1 by Immunohistochemical Staining and Clinicopathological Outcomes in a Multi-Institutional Radical Prostatectomy Cohort of 1067 Patients.

Science.gov (United States)

Brooks, James D; Wei, Wei; Hawley, Sarah; Auman, Heidi; Newcomb, Lisa; Boyer, Hilary; Fazli, Ladan; Simko, Jeff; Hurtado-Coll, Antonio; Troyer, Dean A; Carroll, Peter R; Gleave, Martin; Lance, Raymond; Lin, Daniel W; Nelson, Peter S; Thompson, Ian M; True, Lawrence D; Feng, Ziding; McKenney, Jesse K

2015-01-01

Distinguishing between patients with early stage, screen detected prostate cancer who must be treated from those that can be safely watched has become a major issue in prostate cancer care. Identification of molecular subtypes of prostate cancer has opened the opportunity for testing whether biomarkers that characterize these subtypes can be used as biomarkers of prognosis. Two established molecular subtypes are identified by high expression of the ERG oncoprotein, due to structural DNA alterations that encode for fusion transcripts in approximately ½ of prostate cancers, and over-expression of SPINK1, which is purportedly found only in ERG-negative tumors. We used a multi-institutional prostate cancer tissue microarray constructed from radical prostatectomy samples with associated detailed clinical data and with rigorous selection of recurrent and non-recurrent cases to test the prognostic value of immunohistochemistry staining results for the ERG and SPINK1 proteins. In univariate analysis, ERG positive cases (419/1067; 39%) were associated with lower patient age, pre-operative serum PSA levels, lower Gleason scores (≤ 3+4=7) and improved recurrence free survival (RFS). On multivariate analysis, ERG status was not correlated with RFS, disease specific survival (DSS) or overall survival (OS). High-level SPINK1 protein expression (33/1067 cases; 3%) was associated with improved RFS on univariate and multivariate Cox regression analysis. Over-expression of either protein was not associated with clinical outcome. While expression of ERG and SPINK1 proteins was inversely correlated, it was not mutually exclusive since 3 (0.28%) cases showed high expression of both. While ERG and SPINK1 appear to identify discrete molecular subtypes of prostate cancer, only high expression of SPINK1 was associated with improved clinical outcome. However, by themselves, neither ERG nor SPINK1 appear to be useful biomarkers for prognostication of early stage prostate cancer.

MiR-17-5p impairs trafficking of H-ERG K+ channel protein by targeting multiple er stress-related chaperones during chronic oxidative stress.

Directory of Open Access Journals (Sweden)

Qi Wang

Full Text Available BACKGROUND: To investigate if microRNAs (miRNAs play a role in regulating h-ERG trafficking in the setting of chronic oxidative stress as a common deleterious factor for many cardiac disorders. METHODS: We treated neonatal rat ventricular myocytes and HEK293 cells with stable expression of h-ERG with H2O2 for 12 h and 48 h. Expression of miR-17-5p seed miRNAs was quantified by real-time RT-PCR. Protein levels of chaperones and h-ERG trafficking were measured by Western blot analysis. Luciferase reporter gene assay was used to study miRNA and target interactions. Whole-cell patch-clamp techniques were employed to record h-ERG K(+ current. RESULTS: H-ERG trafficking was impaired by H2O2 after 48 h treatment, accompanied by reciprocal changes of expression between miR-17-5p seed miRNAs and several chaperones (Hsp70, Hsc70, CANX, and Golga2, with the former upregulated and the latter downregulated. We established these chaperones as targets for miR-17-5p. Application miR-17-5p inhibitor rescued H2O2-induced impairment of h-ERG trafficking. Upregulation of endogenous by H2O2 or forced miR-17-5p expression either reduced h-ERG current. Sequestration of AP1 by its decoy molecule eliminated the upregulation of miR-17-5p, and ameliorated impairment of h-ERG trafficking. CONCLUSIONS: Collectively, deregulation of the miR-17-5p seed family miRNAs can cause severe impairment of h-ERG trafficking through targeting multiple ER stress-related chaperones, and activation of AP1 likely accounts for the deleterious upregulation of these miRNAs, in the setting of prolonged duration of oxidative stress. These findings revealed the role of miRNAs in h-ERG trafficking, which may contribute to the cardiac electrical disturbances associated with oxidative stress.

MiR-17-5p impairs trafficking of H-ERG K+ channel protein by targeting multiple er stress-related chaperones during chronic oxidative stress.

Science.gov (United States)

Wang, Qi; Hu, Weina; Lei, Mingming; Wang, Yong; Yan, Bing; Liu, Jun; Zhang, Ren; Jin, Yuanzhe

2013-01-01

To investigate if microRNAs (miRNAs) play a role in regulating h-ERG trafficking in the setting of chronic oxidative stress as a common deleterious factor for many cardiac disorders. We treated neonatal rat ventricular myocytes and HEK293 cells with stable expression of h-ERG with H2O2 for 12 h and 48 h. Expression of miR-17-5p seed miRNAs was quantified by real-time RT-PCR. Protein levels of chaperones and h-ERG trafficking were measured by Western blot analysis. Luciferase reporter gene assay was used to study miRNA and target interactions. Whole-cell patch-clamp techniques were employed to record h-ERG K(+) current. H-ERG trafficking was impaired by H2O2 after 48 h treatment, accompanied by reciprocal changes of expression between miR-17-5p seed miRNAs and several chaperones (Hsp70, Hsc70, CANX, and Golga2), with the former upregulated and the latter downregulated. We established these chaperones as targets for miR-17-5p. Application miR-17-5p inhibitor rescued H2O2-induced impairment of h-ERG trafficking. Upregulation of endogenous by H2O2 or forced miR-17-5p expression either reduced h-ERG current. Sequestration of AP1 by its decoy molecule eliminated the upregulation of miR-17-5p, and ameliorated impairment of h-ERG trafficking. Collectively, deregulation of the miR-17-5p seed family miRNAs can cause severe impairment of h-ERG trafficking through targeting multiple ER stress-related chaperones, and activation of AP1 likely accounts for the deleterious upregulation of these miRNAs, in the setting of prolonged duration of oxidative stress. These findings revealed the role of miRNAs in h-ERG trafficking, which may contribute to the cardiac electrical disturbances associated with oxidative stress.

Isotopes for fundamental research 83mKr for KATRIN and 101Rh and 109Cd for XRD studies on planets

International Nuclear Information System (INIS)

Rasulbaev, Makhsud

2011-01-01

The feasibility of production of 83 Rb from liquid, natural Br at the Bonn Cyclotron was shown. Production of 83 Rb/ 83m Kr generators for KATRIN Collaboration was optimized. 83m Kr release from RbBr residue after the evaporation of the excess Br was studied. A possibility of 83 Rb implantation with 38 % efficiency was shown in the example of non-radioactive 85 Rb implantation. Production optimization of X-ray sources, 101 Rh and 109 Cd, for implementation in XRD analysis set-up at Technical University of Dresden was experimentally investigated at the Bonn Cyclotron. (orig.)

Metallurgical characteristics and fracture mechanical properties of unirradiated Kori-1 RPV weld: Linde 80, WF-233

International Nuclear Information System (INIS)

Hong, Jun Hwa; Lee, B. S.; Oh, Y. J.; Chi, S. H.; Kim, J. H.; Park, D. G.; Yoon, J. H.; Oh, J. M.

2000-07-01

The fracture toughness transition properties of the low upper shelf weld, Linde 80 WF-233, of Kori-1 RPV were evaluated by the master curve method, which is designated by ASTM E 1921, 'Standard test method for determination of reference temperature, T o , for ferritic steels in the transition range'. The reference temperature, T o =-83 deg C, was determined by PCVN specimens at -90 deg C. This value is similar to that of other high copper welds. The initial RT NDT was conservatively estimated as -26 deg F from the current fracture toughness results. From the studies on the chemistry and microstructure, the fracture mechanical properties of WF-233 weld is convincingly not worse than WF-70 and 72W welds

Identifying research priorities in anaesthesia and perioperative care: final report of the joint National Institute of Academic Anaesthesia/James Lind Alliance Research Priority Setting Partnership

OpenAIRE

Boney, O.; Bell, M.; Bell, N.; Conquest, A.; Cumbers, M.; Drake, S.; Galsworthy, M.; Gath, J.; Grocott, M. P.; Harris, E.; Howell, S.; Ingold, A.; Nathanson, M. H.; Pinkney, T.; Metcalf, L.

2015-01-01

Objective To identify research priorities for Anaesthesia and Perioperative Medicine. Design Prospective surveys and consensus meetings guided by an independent adviser. Setting UK. Participants 45 stakeholder organisations (25 professional, 20 patient/carer) affiliated as James Lind Alliance partners. Outcomes First ?ideas-gathering? survey: Free text research ideas and suggestions. Second ?prioritisation? survey: Shortlist of ?summary? research questions (derived from the first survey) rank...

MicroRNA-224 targets ERG2 and contributes to malignant progressions of meningioma

International Nuclear Information System (INIS)

Wang, Maomao; Deng, Xiaodong; Ying, Qi; Jin, Tingyan; Li, Ming; Liang, Chong

2015-01-01

MicroRNA-224 is overexpressed in various malignant tumors with poor prognosis, which plays a critical role in biological processes including cell proliferation, apoptosis and several developmental and physiological progressions. However, the potential association between miR-224 and clinical outcome in patients with meningiomas remains unknown. Here, we investigate miR-224 expression and biological functions in meningiomas. MiR-224 expression was measured by Northern blot analysis and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) in meningioma and normal brain tissues. Kaplan–Meier analysis and Cox regression analysis were used to exam its correlation with clinicopathological features and prognostic value. The biological effects of miR-224 on the cell proliferation and apoptosis in meningioma cells were examined by MTT assay and apoptosis assay. We found the expression levels of miR-224 were significantly higher in meningioma tissues than that in normal brain, positively correlated with advanced pathological grade. Kaplan–Meier analysis indicated that meningioma patients with low miR-224 expression exhibited significantly prolonged overall and recurrence-free survival. Furthermore, we demonstrated that ERG2 was an identical candidate target gene of MiR-224 in vitro. Our results indicated that downregulation of miR-224 suppressed cell growth and resulted in the enhancement of cell apoptosis through activation of the ERG2-BAK-induced apoptosis pathway. Our findings imply the miR-224 expression could predict the overall survival and recurrence-free survival of patients with meningioma and it might be a promising therapeutic target for treating malignant meningiomas. - Highlights: • MiR-224 expression is correlates with prognosis in meningioma patients. • ERG2 is a novel downstream target of miR-224. • MiR-224 suppressed cell growth and enhanced apoptosis in IOMM-Lee and CH157 cells. • MiR-224 is an upstream regulator of the ERG2

Contribution of Interstitial Deletion of 21q22.2-3 per se to Prostate Cancer Progression in Tumors Harboring TMPRSS2-ERG Translocations

Science.gov (United States)

2015-12-01

harboring TMPRSS2- ERG translocations PRINCIPAL INVESTIGATOR: Yan Dong CONTRACTING ORGANIZATION: Tulane University New Orleans, LA 70112...0485 to prostate cancer progression in tumors harboring TMPRSS2- ERG translocations 5b. GRANT NUMBER W81XWH-14-1-0485 5c. PROGRAM ELEMENT NUMBER...Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT TMPRSS2- ERG gene fusions are present in close to 50% of human prostate cancers. Approximately half of the

ERG and FLI1 binding sites demarcate targets for aberrant epigenetic regulation by AML1-ETO in acute myeloid leukemia

NARCIS (Netherlands)

Martens, Joost H. A.; Mandoli, Amit; Simmer, Femke; Wierenga, Bart-Jan; Saeed, Sadia; Singh, Abhishek A.; Altucci, Lucia; Vellenga, Edo; Stunnenberg, Hendrik G.

2012-01-01

ERG and FLI1 are closely related members of the ETS family of transcription factors and have been identified as essential factors for the function and maintenance of normal hematopoietic stem cells. Here genome-wide analysis revealed that both ERG and FLI1 occupy similar genomic regions as AML1-ETO

Vacancy-ordering effects in AlB2-type ErGe2 - x(0.4 < x < or = 0.5).

Science.gov (United States)

Christensen, Jeppe; Lidin, Sven; Malaman, Bernard; Venturini, Gerard

2008-06-01

In the Er-Ge system, the compostion range ErGe(2) to Er(2)Ge(3) has been investigated. Eight samples were produced by arc melting of the elements, and analyzed using X-ray powder diffraction. Nine crystal structures were found to be present in the samples. The structures are described as a homologous series and presented within the superspace formalism using the superspace group X2/m(alpha0gamma)0s, X representing the centring vector ((1/2), (1/2), 0, (1/2)). In this description the modulation vector q = (alphaa* + gammac*) is shown to be a direct measure of the Ge content as ErGe(2 - alpha) (alpha falls in the range 1\\over 3 to (1/2)). The large composition range is achieved by extended vacancy ordering in the planar 6(3) net of Ge with subsequent relaxation.

Study physico-chemical of the sand of the western ERG (Western South Algeria)

Energy Technology Data Exchange (ETDEWEB)

Allam, M.; Tafraoui, A. [Faculty of sciences and technology, University of Bechar (Algeria)], email: allammessaouda@yahoo.fr

2011-07-01

Silica is gaining increasing importance as it is the base for the production of pure silicon, for which several applications are under development in the electronic and solar energy sectors. The aim of this study is to characterize the sand taken from the Western Erg of Algeria to determine the percentage of silicon it contains. Characterization was done through physical analysis to determine the granulometry of the sand. A chemical analysis was next performed, using diffraction of X-rays and a scanning electron microscope to determine the chemical composition of the sand. Results showed that the sand is mainly made of quartz in the form of rounded and subbarrondis grains and that silicon is prevalent, accounting for 98% of the composition. This study demonstrated that sand from the Western Erg of Algeria is rich in silicon and could be used for silicon production.

Functional and Morphological Evaluation of Traumatized Eyes With Berlin's Edema Affecting the Macula Using mfERG, Microperimetry, and SD-OCT.

Science.gov (United States)

Boss, Joseph Daniel; Tosi, Joaquin; Glybina, Inna; Tewari, Asheesh; Abrams, Gary W

2017-02-01

To describe the structural and functional changes that occur in traumatic Berlin's edema involving the macula through assessment with multifocal electroretinogram (mfERG), microperimetry, fundus photography, and spectral-domain optical coherence tomography (SD-OCT). Retrospective case series of five eyes from four patients with macular traumatic Berlin's edema. Patients underwent baseline mfERG (three eyes), MP1 microperimetry (three eyes), fundus photography (five eyes), and SD-OCT (five eyes). All eyes with Berlin's edema showed abnormal findings on baseline SD-OCT, including disruption and fragmentation of the inner segment/ outer segment layer. In two patients with unilateral blunt ocular trauma who underwent mfERG, there was complete loss of the foveal peak in affected eyes. All three eyes that underwent microperimetry showed depressed retinal sensitivity in the area of Berlin's edema. SD-OCT, microperimetry, and mfERG can be used to help diagnose, stratify traumatic severity, and follow structural and functional progression over time in patients with Berlin's edema. [Ophthalmic Surg Lasers Imaging Retina. 2017;48:114-121.]. Copyright 2017, SLACK Incorporated.

The Influence of Brightness on Functional Assessment by mfERG: A Study on Scaffolds Used in Retinal Cell Transplantation in Pigs

Directory of Open Access Journals (Sweden)

A. T. Christiansen

2012-01-01

Full Text Available To determine the effect of membrane brightness on multifocal electroretinograms (mfERGs, we implanted poly lactic-co-glycolic acid (PLGA membranes in the subretinal space of 11 porcine eyes. We compared membranes with their native shiny white color with membranes that were stained with a blue dye (Brilliant Blue. Histological and electrophysiological evaluation of the overlying retina was carried out 6 weeks after implantation. Histologically, both white and blue membranes degraded in a spongiform manner leaving a disrupted outer retina with no preserved photoreceptor segments. Multifocal ERG revealed the white membranes to have a significantly higher P1-amplitude ratio than the blue (P=0.027, and a correlation between brightness ratio and P1-amplitude ratio was found (r=0.762. Based on our findings, we conclude that bright subretinal objects can produce normal mfERG amplitude ratios even when the adjacent photoreceptors are missing. Functional assessment with mfERG in scaffold implant studies should therefore be evaluated with care.

Association of TMPRSS2-ERG gene fusion with clinical characteristics and outcomes: results from a population-based study of prostate cancer

International Nuclear Information System (INIS)

FitzGerald, Liesel M; Cox, Michael E; Ostrander, Elaine A; Stanford, Janet L; Huntsman, David G; Agalliu, Ilir; Johnson, Karynn; Miller, Melinda A; Kwon, Erika M; Hurtado-Coll, Antonio; Fazli, Ladan; Rajput, Ashish B; Gleave, Martin E

2008-01-01

The presence of the TMPRSS2-ERG fusion gene in prostate tumors has recently been associated with an aggressive phenotype, as well as recurrence and death from prostate cancer. These associations suggest the hypothesis that the gene fusion may be used as a prognostic indicator for prostate cancer. In this study, fluorescent in situ hybridization (FISH) assays were used to assess TMPRSS2-ERG fusion status in a group of 214 prostate cancer cases from two population-based studies. The FISH assays were designed to detect both fusion type (deletion vs. translocation) and the number of fusion copies (single vs. multiple). Genotyping of four ERG and one TMPRSS2 SNPs using germline DNA was also performed in a sample of the cases (n = 127). Of the 214 tumors scored for the TMPRSS2-ERG fusion, 64.5% were negative and 35.5% were positive for the fusion. Cases with the TMPRSS2-ERG fusion did not exhibit reduced prostate cancer survival (HR = 0.92, 95% CI = 0.22–3.93), nor was there a significant difference in cause-specific survival when stratifying by translocation or deletion (HR = 0.84, 95% CI = 0.23–3.12) or by the number of retained fusion copies (HR = 1.22, 95% CI = 0.45–3.34). However, evidence for reduced prostate cancer-specific survival was apparent in those cases whose tumor had multiple copies of the fusion. The variant T allele of the TMPRSS2 SNP, rs12329760, was positively associated with TMPRSS2-ERG fusion by translocation (p = 0.05) and with multiple copies of the gene fusion (p = 0.03). If replicated, the results presented here may provide insight into the mechanism by which the TMPRSS2-ERG gene fusion arises and also contribute to diagnostic evaluations for determining the subset of men who will go on to develop metastatic prostate cancer

Voltage-sensing domain mode shift is coupled to the activation gate by the N-terminal tail of hERG channels.

Science.gov (United States)

Tan, Peter S; Perry, Matthew D; Ng, Chai Ann; Vandenberg, Jamie I; Hill, Adam P

2012-09-01

Human ether-a-go-go-related gene (hERG) potassium channels exhibit unique gating kinetics characterized by unusually slow activation and deactivation. The N terminus of the channel, which contains an amphipathic helix and an unstructured tail, has been shown to be involved in regulation of this slow deactivation. However, the mechanism of how this occurs and the connection between voltage-sensing domain (VSD) return and closing of the gate are unclear. To examine this relationship, we have used voltage-clamp fluorometry to simultaneously measure VSD motion and gate closure in N-terminally truncated constructs. We report that mode shifting of the hERG VSD results in a corresponding shift in the voltage-dependent equilibrium of channel closing and that at negative potentials, coupling of the mode-shifted VSD to the gate defines the rate of channel closure. Deletion of the first 25 aa from the N terminus of hERG does not alter mode shifting of the VSD but uncouples the shift from closure of the cytoplasmic gate. Based on these observations, we propose the N-terminal tail as an adaptor that couples voltage sensor return to gate closure to define slow deactivation gating in hERG channels. Furthermore, because the mode shift occurs on a time scale relevant to the cardiac action potential, we suggest a physiological role for this phenomenon in maximizing current flow through hERG channels during repolarization.

Diagnostic Value of ERG in Prostate Needle Biopsies Containing Minute Cancer Foci

Directory of Open Access Journals (Sweden)

Bachurska Svitlana Y.

2017-03-01

Full Text Available Background: Prostate carcinoma (PC is the second most diagnosed cancer in men population worldwide. The small amount of the tissue in prostate needle biopsy is often sufficient for the correct interpretation. Novel antibodies, as ERG, could add to the diagnostic value of IHC study in analysing difficult core biopsies.

Common variants in the hERG (KCNH2) voltage-gated potassium channel are associated with altered fasting and glucose-stimulated plasma incretin and glucagon responses

DEFF Research Database (Denmark)

Engelbrechtsen, Line; Mahendran, Yuvaraj; Jonsson, Anna

2018-01-01

BACKGROUND: Patients with long QT syndrome due to rare loss-of-function mutations in the human ether-á-go-go-related gene (hERG) have prolonged QT interval, risk of arrhythmias, increased secretion of insulin and incretins and impaired glucagon response to hypoglycemia. This is caused by a dysfun......BACKGROUND: Patients with long QT syndrome due to rare loss-of-function mutations in the human ether-á-go-go-related gene (hERG) have prolonged QT interval, risk of arrhythmias, increased secretion of insulin and incretins and impaired glucagon response to hypoglycemia. This is caused...... by a dysfunctional Kv11.1 voltage-gated potassium channel. Based on these findings in patients with rare variants in hERG, we hypothesized that common variants in hERG may also lead to alterations in glucose homeostasis. Subsequently, we aimed to evaluate the effect of two common gain-of-function variants in hERG...... in hERG on QT-interval and circulation levels of incretins, insulin and glucagon. The Danish population-based Inter99 cohort (n = 5895) was used to assess the effect of common variants on QT-interval. The Danish ADDITION-PRO cohort was used (n = 1329) to study genetic associations with levels of GLP-1...

The predictive value of ERG protein expression for development of castration-resistant prostate cancer in hormone-naïve advanced prostate cancer treated with primary androgen deprivation therapy

DEFF Research Database (Denmark)

Berg, Kasper Drimer; Røder, Martin A; Thomsen, Frederik B

2015-01-01

BACKGROUND: Biomarkers predicting response to primary androgen deprivation therapy (ADT) and risk of castration-resistant prostate cancer (CRPC) is lacking. We aimed to analyse the predictive value of ERG expression for development of CRPC. METHODS: In total, 194 patients with advanced and....../or metastatic prostate cancer (PCa) treated with first-line castration-based ADT were included. ERG protein expression was analysed in diagnostic specimens using immunohistochemistry (anti-ERG, EPR3864). Time to CRPC was compared between ERG subgroups using multiple cause-specific Cox regression stratified......-negative group, respectively. Compared to a model omitting ERG-status, the ERG-stratified model showed comparable AUC values 1 year (77.6% vs. 78.0%, P = 0.82), 2 years (71.7% vs. 71.8%, P = 0.85), 5 years (68.5% vs. 69.9%, P = 0.32), and 8 years (67.9% vs. 71.4%, P = 0.21) from ADT initiation. No differences...

Draft Genome Sequence of MCPA-Degrading Sphingomonas sp. Strain ERG5, Isolated from a Groundwater Aquifer in Denmark

DEFF Research Database (Denmark)

Nielsen, Tue Kjærgaard; Kot, Witold; Sørensen, Sebastian R

2015-01-01

Sphingomonas sp. strain ERG5 was isolated from a bacterial community, originating from a groundwater aquifer polluted with low pesticide concentrations. This bacterium degrades 2-methyl-4-chlorophenoxyacetic acid (MCPA) in a wide spectrum of concentrations and has been shown to function in bioaug......Sphingomonas sp. strain ERG5 was isolated from a bacterial community, originating from a groundwater aquifer polluted with low pesticide concentrations. This bacterium degrades 2-methyl-4-chlorophenoxyacetic acid (MCPA) in a wide spectrum of concentrations and has been shown to function...

Nain's Hierarchy of Needs: An Alternative to Maslow's & ERG's Hierarchy of Needs

OpenAIRE

nain, bhavya

2013-01-01

This article gives reasons as to why Maslow's & ERG Theory of Needs is inaccurate. It also gives reasons why the same is inaccurate in an organizational perspective. The author also gives a alternative model of needs, namely the Nain Model, which is particularly applicable in an organizational perspective. This article has been written for those interested in Organizational Behaviour.

Rapid detection of ERG11 gene mutations in clinical Candida albicans isolates with reduced susceptibility to fluconazole by rolling circle amplification and DNA sequencing

Directory of Open Access Journals (Sweden)

Ellis David

2009-08-01

Full Text Available Abstract Background Amino acid substitutions in the target enzyme Erg11p of azole antifungals contribute to clinically-relevant azole resistance in Candida albicans. A simple molecular method for rapid detection of ERG11 gene mutations would be an advantage as a screening tool to identify potentially-resistant strains and to track their movement. To complement DNA sequencing, we developed a padlock probe and rolling circle amplification (RCA-based method to detect a series of mutations in the C. albicans ERG11 gene using "reference" azole-resistant isolates with known mutations. The method was then used to estimate the frequency of ERG11 mutations and their type in 25 Australian clinical C. albicans isolates with reduced susceptibility to fluconazole and in 23 fluconazole-susceptible isolates. RCA results were compared DNA sequencing. Results The RCA assay correctly identified all ERG11 mutations in eight "reference" C. albicans isolates. When applied to 48 test strains, the RCA method showed 100% agreement with DNA sequencing where an ERG11 mutation-specific probe was used. Of 20 different missense mutations detected by sequencing in 24 of 25 (96% isolates with reduced fluconazole susceptibility, 16 were detected by RCA. Five missense mutations were detected by both methods in 18 of 23 (78% fluconazole-susceptible strains. DNA sequencing revealed that mutations in non-susceptible isolates were all due to homozygous nucleotide changes. With the exception of the mutations leading to amino acid substitution E266D, those in fluconazole-susceptible strains were heterozygous. Amino acid substitutions common to both sets of isolates were D116E, E266D, K128T, V437I and V488I. Substitutions unique to isolates with reduced fluconazole susceptibility were G464 S (n = 4 isolates, G448E (n = 3, G307S (n = 3, K143R (n = 3 and Y123H, S405F and R467K (each n = 1. DNA sequencing revealed a novel substitution, G450V, in one isolate. Conclusion The sensitive RCA

Overexpression of erg1 gene in Trichoderma harzianum CECT 2413: effect on the induction of tomato defence-related genes.

Science.gov (United States)

Cardoza, R E; Malmierca, M G; Gutiérrez, S

2014-09-01

To investigate the effect of the overexpression of erg1 gene of Trichoderma harzianum CECT 2413 (T34) on the Trichoderma-plant interactions and in the biocontrol ability of this fungus. Transformants of T34 strain overexpressing erg1 gene did not show effect on the ergosterol level, although a drastic decrease in the squalene level was observed in the transformants at 96 h of growth. During interaction with plants, the erg1 overexpression resulted in a reduction of the priming ability of several tomato defence-related genes belonging to the salicylate pathway, and also of the TomLoxA gene, which is related to the jasmonate pathway. Interestingly, other jasmonate-related genes, such as PINI and PINII, were slightly induced. The erg1 overexpressed transformants also showed a reduced ability to colonize tomato roots. The ergosterol biosynthetic pathway might play an important role in regulating Trichoderma-plant interactions, although this role does not seem to be restricted to the final product; instead, other intermediates such as squalene, whose role in the Trichoderma-plant interaction has not been characterized, would also play an important role. The functional analysis of genes involved in the synthesis of ergosterol could provide additional strategies to improve the ability of biocontrol of the Trichoderma strains and their interaction with plants. © 2014 The Society for Applied Microbiology.

MiR-17-5p Impairs Trafficking of H-ERG K+ Channel Protein by Targeting Multiple ER Stress-Related Chaperones during Chronic Oxidative Stress

OpenAIRE

Wang, Qi; Hu, Weina; Lei, Mingming; Wang, Yong; Yan, Bing; Liu, Jun; Zhang, Ren; Jin, Yuanzhe

2013-01-01

BACKGROUND: To investigate if microRNAs (miRNAs) play a role in regulating h-ERG trafficking in the setting of chronic oxidative stress as a common deleterious factor for many cardiac disorders. METHODS: We treated neonatal rat ventricular myocytes and HEK293 cells with stable expression of h-ERG with H2O2 for 12 h and 48 h. Expression of miR-17-5p seed miRNAs was quantified by real-time RT-PCR. Protein levels of chaperones and h-ERG trafficking were measured by Western blot analysis. Lucifer...

The role of hERG1 ion channels in epithelial-mesenchymal transition and the capacity of riluzole to reduce cisplatin resistance in colorectal cancer cells.

Science.gov (United States)

Fortunato, Angelo

2017-08-01

The transition of cells from the epithelial to the mesenchymal state (EMT) plays an important role in tumor progression. EMT allows cells to acquire mobility, stem-like behavior and resistance to apoptosis and drug treatment. These features turn EMT into a central process in tumor biology. Ion channels are attractive targets for the treatment of cancer since they play critical roles in controlling a wide range of physiological processes that are frequently deregulated in cancer. Here, we investigated the role of ether-a-go-go-related 1 (hERG1) ion channels in the EMT of colorectal cancer cells. We studied the epithelial-mesenchymal profile of different colorectal cancer-derived cell lines and the expression of hERG1 potassium channels in these cell lines using real-time PCR. Next, we knocked down hERG1 expression in HCT116 cells using lentivirus mediated RNA interference and characterized the hERG1 silenced cells in vitro and in vivo. Finally, we investigated the capacity of riluzole, an ion channel-modulating drug used in humans to treat amyotrophic lateral sclerosis, to reduce the resistance of the respective colorectal cancer cells to the chemotherapeutic drug cisplatin. We found that of the colorectal cancer-derived cell lines tested, HCT116 showed the highest mesenchymal profile and a high hERG1 expression. Subsequent hERG1 expression knockdown induced a change in cell morphology, which was accompanied by a reduction in the proliferative and tumorigenic capacities of the cells. Notably, we found that hERG1expression knockdown elicited a reversion of the EMT profile in HCT116 cells with a reacquisition of the epithelial-like profile. We also found that riluzole increased the sensitivity of HCT116 cisplatin-resistant cells to cisplatin. Our data indicate that hERG1 plays a role in the EMT of colorectal cancer cells and that its knockdown reduces the proliferative and tumorigenic capacities of these cells. In addition, we conclude that riluzole may be used in

Large Pilot Scale Testing of Linde/BASF Post-Combustion CO₂ Capture Technology at the Abbott Coal-Fired Power Plant

Energy Technology Data Exchange (ETDEWEB)

O' Brien, Kevin C. [University of Illinois, Champaign, IL (United States)

2017-08-18

The work summarized in this report is the first step towards a project that will re-train and create jobs for personnel in the coal industry and continue regional economic development to benefit regions impacted by previous downturns. The larger project is aimed at capturing ~300 tons/day (272 metric tonnes/day) CO₂ at a 90% capture rate from existing coal- fired boilers at the Abbott Power Plant on the campus of University of Illinois (UI). It will employ the Linde-BASF novel amine-based advanced CO₂ capture technology, which has already shown the potential to be cost-effective, energy efficient and compact at the 0.5-1.5 MWe pilot scales. The overall objective of the project is to design and install a scaled-up system of nominal 15 MWe size, integrate it with the Abbott Power Plant flue gas, steam and other utility systems, and demonstrate the viability of continuous operation under realistic conditions with high efficiency and capacity. The project will also begin to build a workforce that understands how to operate and maintain the capture plants by including students from regional community colleges and universities in the operation and evaluation of the capture system. This project will also lay the groundwork for follow-on projects that pilot utilization of the captured CO₂ from coal-fired power plants. The net impact will be to demonstrate a replicable means to (1) use a standardized procedure to evaluate power plants for their ability to be retrofitted with a pilot capture unit; (2) design and construct reliable capture systems based on the Linde-BASF technology; (3) operate and maintain these systems; (4) implement training programs with local community colleges and universities to establish a workforce to operate and maintain the systems; and (5) prepare to evaluate at the large pilot scale level various methods to utilize the resulting captured CO₂. Towards the larger project goal, the UI-led team, together

Tubin: Sinfonie nr. 11 (ergänzt von Kaljo Raid) / Christoph Schlüren

Index Scriptorium Estoniae

Schlüren, Christoph

1997-01-01

Uuest heliplaadist "Tubin: Sinfonie nr. 11 (ergänzt von Kaljo Raid); Pärt: Nekrolog op. 5, Sinfonie nr. 1; Tüür: Searching for Roots, Insula deserta, Zeitraum. Königliches Philharmonisches Orchester Stockholm, Paavo Järvi". Virgin/EMI CD 5 45212 2 (WD:71'34") DDD

Validation and Clinical Utility of the hERG IC50:Cmax Ratio to Determine the Risk of Drug-Induced Torsades de Pointes: A Meta-Analysis.

Science.gov (United States)

Lehmann, David F; Eggleston, William D; Wang, Dongliang

2018-03-01

Use of the QT interval corrected for heart rate (QTc) on the electrocardiogram (ECG) to predict torsades de pointes (TdP) risk from culprit drugs is neither sensitive nor specific. The ratio of the half-maximum inhibitory concentration of the hERG channel (hERG IC50) to the peak serum concentration of unbound drug (C max ) is used during drug development to screen out chemical entities likely to cause TdP. To validate the use of the hERG IC50:C max ratio to predict TdP risk from a culprit drug by its correlation with TdP incidence. Medline (between 1966 and March 2017) was accessed for hERG IC50 and C max values from the antihistamine, fluoroquinolone, and antipsychotic classes to identify cases of drug-induced TdP. Exposure to a culprit drug was estimated from annual revenues reported by the manufacturer. Inclusion criteria for TdP cases were provision of an ECG tracing that demonstrated QTc prolongation with TdP and normal serum values of potassium, calcium, and magnesium. Cases reported in patients with a prior rhythm disturbance and those involving a drug interaction were excluded. The Meta-Analysis of Observational Studies in Epidemiology checklist was used for epidemiological data extraction by two authors. Negligible risk drugs were defined by an hERG IC50:C max ratio that correlated with less than a 5% chance of one TdP event for every 100 million exposures (relative risk [RR] 1.0). The hERG IC50:C max ratio correlated with TdP risk (0.312; 95% confidence interval 0.205-0.476, pratio of 80 (RR 1.0). The RR from olanzapine is on par with loratadine; ziprasidone is comparable with ciprofloxacin. Drugs with an RR greater than 50 include astemizole, risperidone, haloperidol, and thioridazine. The hERG IC50:C max ratio was correlated with TdP incidence for culprit drugs. This validation provides support for the potential use of the hERG IC50:C max ratio for clinical decision making in instances of drug selection where TdP risk is a concern. © 2018

Isotopes for fundamental research {sup 83m}Kr for KATRIN and {sup 101}Rh and {sup 109}Cd for XRD studies on planets

Energy Technology Data Exchange (ETDEWEB)

Rasulbaev, Makhsud

2011-12-16

The feasibility of production of {sup 83}Rb from liquid, natural Br at the Bonn Cyclotron was shown. Production of {sup 83}Rb/{sup 83m}Kr generators for KATRIN Collaboration was optimized. {sup 83m}Kr release from RbBr residue after the evaporation of the excess Br was studied. A possibility of {sup 83}Rb implantation with 38 % efficiency was shown in the example of non-radioactive {sup 85}Rb implantation. Production optimization of X-ray sources, {sup 101}Rh and {sup 109}Cd, for implementation in XRD analysis set-up at Technical University of Dresden was experimentally investigated at the Bonn Cyclotron. (orig.)

Oxycodone is associated with dose-dependent QTc prolongation in patients and low-affinity inhibiting of hERG activity in vitro

DEFF Research Database (Denmark)

Fanoe, Søren; Jensen, Gorm Boje; Sjøgren, Per

2008-01-01

with the use of these drugs. WHAT THIS PAPER ADDS: This study is the first to show that oxycodone dose is associated with QT prolongation and in vitro blockade of hERG channels expressed in HEK293. Neither morphine nor tramadol doses are associated with the QT interval length. AIMS: During recent years some...... and TdP could be a more general problem associated with the use of these drugs. The aims of this study were to evaluate the association between different opioids and the QTc among patients and measure hERG activity under influence by opioids in vitro. METHODS: One hundred chronic nonmalignant pain...... patients treated with methadone, oxycodone, morphine or tramadol were recruited in a cross-sectional study. The QTc was estimated from a 12-lead ECG. To examine hERG activity in the presence of oxycodone, electrophysiological testing was conducted using Xenopus laevis oocytes and HEK293 cells expressing h...

Constituents in oil field produced waters discharged into the Loch Katrine wetland complex, Park County, Wyoming, and their bioconcentration in the aquatic bird food chain

International Nuclear Information System (INIS)

Ramirez, P. Jr.

1993-01-01

Trace elements, hydrocarbons and radium-226 concentrations were analyzed in water, sediment and biota from the Loch Katrine wetlands at Park County, WY in 1992. This study was designed to determine if produced waters pose a risk to aquatic birds inhabiting the wetlands. The radium-226 concentration recorded at the Sidney Battery Discharge in July, 93.7 pCi/l, exceeded WY DEQ's 60 pCi/l standard for the protection of aquatic life. Water quality acute criteria were exceeded for arsenic, Custer Lake, July, and for zinc, Sidney Battery discharge, April. Radium-226 concentrations in sediments from Custer Lake and Sidney Battery Discharge exceeded the 3 pCi/g background for Oregon Basin soils. The radium-226 concentration in aquatic vegetation, Custer Lake, 29.5 pCi/g, greatly exceeded the 2.9 pCi/g average concentration found in plants growing in uranium mill tailings in South Dakota. Radium-226 in aquatic vegetation may be available to aquatic birds. Oil and grease concentrations, Sidney Battery Discharge, exceeded the 10 mg/l standard of WY DEQ. Sediment hydrocarbon concentrations were highest at Sidney Battery Discharge, 6.376 μg/g, followed by Custer Lake, 1.104 μg/g. Benzo(a)pyrene was not detected in gadwalls from Loch Katrine but was detected in northern shovelers from Custer Lake. Benzo(a)pyrene concentrations in northern shoveler bile ranged from 500 to 960 ng/g (ppb) wet weight. Benzo(a)pyrene concentrations in shovelers is indicative of exposure to petroleum hydrocarbons

Performance of Machine Learning Algorithms for Qualitative and Quantitative Prediction Drug Blockade of hERG1 channel.

Science.gov (United States)

Wacker, Soren; Noskov, Sergei Yu

2018-05-01

Drug-induced abnormal heart rhythm known as Torsades de Pointes (TdP) is a potential lethal ventricular tachycardia found in many patients. Even newly released anti-arrhythmic drugs, like ivabradine with HCN channel as a primary target, block the hERG potassium current in overlapping concentration interval. Promiscuous drug block to hERG channel may potentially lead to perturbation of the action potential duration (APD) and TdP, especially when with combined with polypharmacy and/or electrolyte disturbances. The example of novel anti-arrhythmic ivabradine illustrates clinically important and ongoing deficit in drug design and warrants for better screening methods. There is an urgent need to develop new approaches for rapid and accurate assessment of how drugs with complex interactions and multiple subcellular targets can predispose or protect from drug-induced TdP. One of the unexpected outcomes of compulsory hERG screening implemented in USA and European Union resulted in large datasets of IC 50 values for various molecules entering the market. The abundant data allows now to construct predictive machine-learning (ML) models. Novel ML algorithms and techniques promise better accuracy in determining IC 50 values of hERG blockade that is comparable or surpassing that of the earlier QSAR or molecular modeling technique. To test the performance of modern ML techniques, we have developed a computational platform integrating various workflows for quantitative structure activity relationship (QSAR) models using data from the ChEMBL database. To establish predictive powers of ML-based algorithms we computed IC 50 values for large dataset of molecules and compared it to automated patch clamp system for a large dataset of hERG blocking and non-blocking drugs, an industry gold standard in studies of cardiotoxicity. The optimal protocol with high sensitivity and predictive power is based on the novel eXtreme gradient boosting (XGBoost) algorithm. The ML-platform with XGBoost

``High energy Electron exPeriment (HEP)'' onboard the ERG satellite

Science.gov (United States)

Mitani, T.; Takashima, T.; Kasahara, S.; Miyake, W.; Hirahara, M.

2017-12-01

The Exploration of energization and Radiation in Geospace (ERG) satellite was successfully launched on December 20, 2016, and now explores how relativistic electrons in the radiation belts are generated during space storms. "High energy Electron exPeriment (HEP)" onboard the ERG satellite observes 70 keV - 2 MeV electrons and provides three-dimensional velocity distribution of electrons every spacecraft spin period. Electrons are observed by two types of camera designs, HEP-L and HEP-H, with regard to geometrical factor and energy range. HEP-L observes 0.1 - 1 MeV electrons and its geometrical factor (G-factor) is 10-3 cm2 str, and HEP-H observes 0.7 - 2 MeV and G-factor is 10-2 cm2 str. HEP-L and HEP-H each consist of three pin-hole type cameras, and each camera consist of mechanical collimator, stacked silicon semiconductor detectors and readout ASICs. HEP-H has larger opening angle of the collimator and more silicon detectors to observe higher energy electrons than HEP-L. The initial checkout in orbit was carried out in February 2017 and it was confirmed that there was no performance degradation by comparing the results of the initial checkout in orbit and the prelaunch function tests. Since late March, HEP has carried out normal observation. HEP observed losses and recovery of the outer radiation belt electrons several times up to now. In this presentation we introduce the HEP instrument design, prelaunch tests results and report the initial results in orbit.

Evolution of clinical research: A history before and beyond james lind

Directory of Open Access Journals (Sweden)

Arun Bhatt

2010-01-01

Full Text Available The evolution of clinical research traverses a long and fascinating journey. From the first recorded trial of legumes in biblical times to the first randomized controlled of trial of streptomycin in 1946, the history of clinical trial covers a wide variety of challenges - scientific, ethical and regulatory. The famous 1747 scurvy trial conducted by James Lind contained most elements of a controlled trial. The UK Medical Research Council′s (MRC trial of patulin for common cold in 1943 was the first double blind controlled trial. This paved the way for the first randomized control trial of streptomycin in pulmonary tuberculosis carried out in 1946 by MRC of the UK. This landmark trial was a model of meticulousness in design and implementation, with systematic enrolment criteria and data collection compared with the ad hoc nature of other contemporary research. Over the years, as the discipline of controlled trials grew in sophistication and influence, the streptomycin trial continues to be referred to as ground breaking. The ethical advances in human protection include several milestones - Nuremberg Code, Declaration of Helsinki, Belmont Report, and 1996, International Conference on Harmonization Good Clinical Practice guidance. In parallel to ethical guidelines, clinical trials started to become embodied in regulation as government authorities began recognizing a need for controlling medical therapies in the early 20th century. As the scientific advances continue to occur, there will be new ethical and regulatory challenges requiring dynamic updates in ethical and legal framework of clinical trials.

Facultative Sterol Uptake in an Ergosterol-Deficient Clinical Isolate of Candida glabrata Harboring a Missense Mutation in ERG11 and Exhibiting Cross-Resistance to Azoles and Amphotericin B

Science.gov (United States)

Hull, Claire M.; Parker, Josie E.; Bader, Oliver; Weig, Michael; Gross, Uwe; Warrilow, Andrew G. S.; Kelly, Diane E.

2012-01-01

We identified a clinical isolate of Candida glabrata (CG156) exhibiting flocculent growth and cross-resistance to fluconazole (FLC), voriconazole (VRC), and amphotericin B (AMB), with MICs of >256, >256, and 32 μg ml−1, respectively. Sterol analysis using gas chromatography-mass spectrometry (GC-MS) revealed that CG156 was a sterol 14α-demethylase (Erg11p) mutant, wherein 14α-methylated intermediates (lanosterol was >80% of the total) were the only detectable sterols. ERG11 sequencing indicated that CG156 harbored a single-amino-acid substitution (G315D) which nullified the function of native Erg11p. In heterologous expression studies using a doxycycline-regulatable Saccharomyces cerevisiae erg11 strain, wild-type C. glabrata Erg11p fully complemented the function of S. cerevisiae sterol 14α-demethylase, restoring growth and ergosterol synthesis in recombinant yeast; mutated CG156 Erg11p did not. CG156 was culturable using sterol-free, glucose-containing yeast minimal medium (glcYM). However, when grown on sterol-supplemented glcYM (with ergosta 7,22-dienol, ergosterol, cholestanol, cholesterol, Δ7-cholestenol, or desmosterol), CG156 cultures exhibited shorter lag phases, reached higher cell densities, and showed alterations in cellular sterol composition. Unlike comparator isolates (harboring wild-type ERG11) that became less sensitive to FLC and VRC when cultured on sterol-supplemented glcYM, facultative sterol uptake by CG156 did not affect its azole-resistant phenotype. Conversely, CG156 grown using glcYM with ergosterol (or with ergosta 7,22-dienol) showed increased sensitivity to AMB; CG156 grown using glcYM with cholesterol (or with cholestanol) became more resistant (MICs of 2 and >64 μg AMB ml−1, respectively). Our results provide insights into the consequences of sterol uptake and metabolism on growth and antifungal resistance in C. glabrata. PMID:22615281

The human ether-a-go-go-related gene (hERG) current inhibition selectively prolongs action potential of midmyocardial cells to augment transmural dispersion.

Science.gov (United States)

Yasuda, C; Yasuda, S; Yamashita, H; Okada, J; Hisada, T; Sugiura, S

2015-08-01

The majority of drug induced arrhythmias are related to the prolongation of action potential duration following inhibition of rapidly activating delayed rectifier potassium current (I(Kr)) mediated by the hERG channel. However, for arrhythmias to develop and be sustained, not only the prolongation of action potential duration but also its transmural dispersion are required. Herein, we evaluated the effect of hERG inhibition on transmural dispersion of action potential duration using the action potential clamp technique that combined an in silico myocyte model with the actual I(Kr) measurement. Whole cell I(Kr) current was measured in Chinese hamster ovary cells stably expressing the hERG channel. The measured current was coupled with models of ventricular endocardial, M-, and epicardial cells to calculate the action potentials. Action potentials were evaluated under control condition and in the presence of 1, 10, or 100 μM disopyramide, an hERG inhibitor. Disopyramide dose-dependently increased the action potential durations of the three cell types. However, action potential duration of M-cells increased disproportionately at higher doses, and was significantly different from that of epicardial and endocardial cells (dispersion of repolarization). By contrast, the effects of disopyramide on peak I(Kr) and instantaneous current-voltage relation were similar in all cell types. Simulation study suggested that the reduced repolarization reserve of M-cell with smaller amount of slowly activating delayed rectifier potassium current levels off at longer action potential duration to make such differences. The action potential clamp technique is useful for studying the mechanism of arrhythmogenesis by hERG inhibition through the transmural dispersion of repolarization.

The Study of the plasmaspheric refilling using the data from the ERG, the VAPs, the ground-based magnetometers and the IPE model

Science.gov (United States)

Obana, Y.; Maruyama, N.; Masahito, N.; Matsuoka, A.; Teramoto, M.; Nomura, R.; Fujimoto, A.; Tanaka, Y.; Shinohara, M.; Kasahara, Y.; Matsuda, S.; Kumamoto, A.; Tsuchiya, F.; Yoshizumi, M.; Shinohara, I.

2017-12-01

Earth's inner magnetosphere is a complex dynamical region of geo space comprising plasma populations with wide energy ranges, the plasmasphere, ring current, and radiation belts. They form a closely coupled system, thus, the plasmasphere is the lowest energy population in the inner magnetosphere, but the accurate prediction of the evolution of the plasmasphere is critical in understanding the dynamics of the inner magnetosphere, which include even the highest energy population, the radiation belts. In this study, we study plasmaspheric refilling following geomagnetic storms using data from ERG-MGF, ERG-PWE, RBSP-EMFISIS and Ground-based magneto­meters. DC magnetic field data measured by ERG-MGF, RBSP-EMFISIS and ground-based magnetometers provides the frequency of the toroidal mode field line resonances. From this information, the equatorial plasma mass density is estimated by solving the MHD wave equation for suitable models of the magnetic field and the field line density distribution. ERG-PWE and RBSP-EMFISIS provide measurements of wave electric and magnetic field, thus we can estimate the local electron density from the plasma wave spectrograms by identifying narrow-band emission at the upper-hybrid resonance frequency. Furthermore, using Ionosphere Plasmasphere Electrodynamics Model (IPE), we calculate the plasmaspheric refilling rates and evaluate the relative contribution of various mechanisms (heating, neutral particle density, composition and wings, etc.) to the refilling rate.

Monitoring the energy scale of KATRIN with conversion electrons of a solid {sup 83m}Kr source as nuclear standard

Energy Technology Data Exchange (ETDEWEB)

Schloesser, Klaus [IKP, Karlsruher Institut fuer Technologie (Germany); Collaboration: KATRIN-Collaboration

2016-07-01

For KATRIN to be able to achieve the desired sensitivity of 200 meV/c{sup 2} for the effective electron neutrino mass, it is of crucial importance that the energy scale of the main spectrometer (18.6 keV) is under control within +/-60 mV at any given time over the planned measurement time of approximately 5 years. Besides conventional high voltage dividers and high precision volt meters, a nuclear standard will be deployed additionally in a separate spectrometer of MAC-E filter type. The filter electrodes of both spectrometers are connected galvanically. For permanent and continuous monitoring an easy to use ion implanted source containing the noble gas {sup 83m}Kr was developed and qualified for HV monitoring at the ppm level in the 30 kV regime. This talk presents the methods applied and the achievements made.

Structural refinement of the hERG1 pore and voltage-sensing domains with ROSETTA-membrane and molecular dynamics simulations.

Science.gov (United States)

Subbotina, Julia; Yarov-Yarovoy, Vladimir; Lees-Miller, James; Durdagi, Serdar; Guo, Jiqing; Duff, Henry J; Noskov, Sergei Yu

2010-11-01

The hERG1 gene (Kv11.1) encodes a voltage-gated potassium channel. Mutations in this gene lead to one form of the Long QT Syndrome (LQTS) in humans. Promiscuous binding of drugs to hERG1 is known to alter the structure/function of the channel leading to an acquired form of the LQTS. Expectably, creation and validation of reliable 3D model of the channel have been a key target in molecular cardiology and pharmacology for the last decade. Although many models were built, they all were limited to pore domain. In this work, a full model of the hERG1 channel is developed which includes all transmembrane segments. We tested a template-driven de-novo design with ROSETTA-membrane modeling using side-chain placements optimized by subsequent molecular dynamics (MD) simulations. Although backbone templates for the homology modeled parts of the pore and voltage sensors were based on the available structures of KvAP, Kv1.2 and Kv1.2-Kv2.1 chimera channels, the missing parts are modeled de-novo. The impact of several alignments on the structure of the S4 helix in the voltage-sensing domain was also tested. Herein, final models are evaluated for consistency to the reported structural elements discovered mainly on the basis of mutagenesis and electrophysiology. These structural elements include salt bridges and close contacts in the voltage-sensor domain; and the topology of the extracellular S5-pore linker compared with that established by toxin foot-printing and nuclear magnetic resonance studies. Implications of the refined hERG1 model to binding of blockers and channels activators (potent new ligands for channel activations) are discussed. © 2010 Wiley-Liss, Inc.

What are the dietary treatment research priorities for inflammatory bowel disease? A short report based on a priority setting partnership with the James Lind Alliance.

Science.gov (United States)

Lomer, M C; Hart, A L; Verjee, A; Daly, A; Solomon, J; Mclaughlin, J

2017-12-01

Treatment of inflammatory bowel disease (IBD) involves a multidisciplinary approach comprising medical management and sometimes surgery. Although diet is central to IBD management, the optimal diet for patients with IBD is uncertain. A UK collaborative partnership within the James Lind Alliance was set up between patients, clinicians and other stakeholders to develop research priorities in IBD. The aim of this short report is to provide a comprehensive summary of the research priority findings relating to diet in the treatment of IBD. The James Lind Alliance Priority Setting Partnership process was used to develop research priorities in IBD. In brief, patients, clinicians and other stakeholders were invited to provide up to five treatment uncertainties in IBD. These uncertainties were collated, revised and ranked, leading to a final top 10 research questions in IBD. A total of 1671 uncertainties from 531 participants were collected and refined to exclude duplicates leaving 1253 uncertainties. Of these, 348 were categorised as diet-related and grouped according to topic. There were 206 uncertainties related to how diet can be used to treat IBD or alleviate symptoms. Seventy-two percent of diet-related questions came from patients. One broadly diet-related and two diet-specific treatment uncertainties were included in the top 10 research priorities for IBD. Dietary treatment options in the management of IBD are important research priorities. Almost three-quarters of diet related questions came from patients, who were particularly interested in how diet can impact disease activity and symptom control. © 2017 The British Dietetic Association Ltd.

Enhanced oxidative killing of azole-resistant Candida glabrata strains with ERG11 deletion.

Science.gov (United States)

Kan, V L; Geber, A; Bennett, J E

1996-01-01

The susceptibility of genetically defined Candida glabrata strains to killing by H2O2 and neutrophils was assessed. Fluconazole-susceptible L5L and L5D strains demonstrated survival rates higher than those of two fluconazole-resistant strains lacking the ERG11 gene coding for 14 alpha-demethylase. Fluconazole resistance can occur by mechanisms which increase fungal susceptibility to oxidative killing by H2O2 and neutrophils. PMID:8807069

hERG classification model based on a combination of support vector machine method and GRIND descriptors

DEFF Research Database (Denmark)

Li, Qiyuan; Jorgensen, Flemming Steen; Oprea, Tudor

2008-01-01

and diverse library of 495 compounds. The models combine pharmacophore-based GRIND descriptors with a support vector machine (SVM) classifier in order to discriminate between hERG blockers and nonblockers. Our models were applied at different thresholds from 1 to 40 mu m and achieved an overall accuracy up...

Onboard Processing on PWE OFA/WFC (Onboard Frequency Analyzer/Waveform Capture) aboard the ERG (ARASE) Satellite

Science.gov (United States)

Matsuda, S.; Kasahara, Y.; Kojima, H.; Kasaba, Y.; Yagitani, S.; Ozaki, M.; Imachi, T.; Ishisaka, K.; Kurita, S.; Ota, M.; Kumamoto, A.; Tsuchiya, F.; Yoshizumi, M.; Matsuoka, A.; Teramoto, M.; Shinohara, I.

2017-12-01

Exploration of energization and Radiation in Geospace (ERG) is a mission for understanding particle acceleration, loss mechanisms, and the dynamic evolution of space storms in the context of cross-energy and cross-regional coupling [Miyoshi et al., 2012]. The ERG (ARASE) satellite was launched on December 20, 2016, and successfully inserted into an orbit. The Plasma Wave Experiment (PWE) is one of the science instruments on board the ERG satellite to measure electric field and magnetic field in the inner magnetosphere. PWE consists of three sub-components, EFD (Electric Field Detector), OFA/WFC (Onboard Frequency Analyzer and Waveform Capture), and HFA (High Frequency Analyzer). Especially, OFA/WFC measures electric and magnetic field spectrum and waveform from a few Hz to 20 kHz. OFA/WFC processes signals detected by a couple of dipole wire-probe antenna (WPT) and tri-axis magnetic search coils (MSC) installed onboard the satellite. The PWE-OFA subsystem calculates and produces three kind of data; OFA-SPEC (power spectrum), OFA-MATRIX (spectrum matrix), and OFA-COMPLEX (complex spectrum). They are continuously processed 24 hours per day and all data are sent to the ground. OFA-MATRIX and OFA-COMPLEX are used for polarization analyses and direction finding of the plasma waves. The PWE-WFC subsystem measures raw (64 kHz sampled) and down-sampled (1 kHz sampled) burst waveform detected by the WPT and the MSC sensors. It activates by a command, automatic triggering, and scheduling. The initial check-out process of the PWE successfully completed, and initial data has been obtained. In this presentation, we introduce onboard processing technique on PWE OFA/WFC and its initial results.

In silico analysis of conformational changes induced by mutation of aromatic binding residues: consequences for drug binding in the hERG K+ channel.

Directory of Open Access Journals (Sweden)

Kirsten Knape

Full Text Available Pharmacological inhibition of cardiac hERG K(+ channels is associated with increased risk of lethal arrhythmias. Many drugs reduce hERG current by directly binding to the channel, thereby blocking ion conduction. Mutation of two aromatic residues (F656 and Y652 substantially decreases the potency of numerous structurally diverse compounds. Nevertheless, some drugs are only weakly affected by mutation Y652A. In this study we utilize molecular dynamics simulations and docking studies to analyze the different effects of mutation Y652A on a selected number of hERG blockers. MD simulations reveal conformational changes in the binding site induced by mutation Y652A. Loss of π-π-stacking between the two aromatic residues induces a conformational change of the F656 side chain from a cavity facing to cavity lining orientation. Docking studies and MD simulations qualitatively reproduce the diverse experimentally observed modulatory effects of mutation Y652A and provide a new structural interpretation for the sensitivity differences.

On the long wavelength thermodynamic limit of a neutron diffraction experiment in the vicinity of a liquid-liquid critical point. Application to the concentration fluctuations in the Li-ND3 system

International Nuclear Information System (INIS)

Chieux, P.; Damay, P.

1978-01-01

A quantitative comparison is made between the thermodynamics as obtained from the long wavelength limit of a small angle neutron scattering experiment in the vicinity of a liquid-liquid critical point for the Li-ND 3 system and the data obtained from vapour pressure measurements. The agreement is fair. It is shown how the comparison always implies an underlying model of the interacting species leading to the liquid-liquid phase separation. (Auth.)

Rapid detection of ERG11 gene mutations in clinical Candida albicans isolates with reduced susceptibility to fluconazole by rolling circle amplification and DNA sequencing

OpenAIRE

Wang, Huiping; Kong, Fanrong; Sorrell, Tania C; Wang, Bin; McNicholas, Paul; Pantarat, Namfon; Ellis, David; Xiao, Meng; Widmer, Fred; Chen, Sharon CA

2009-01-01

Abstract Background Amino acid substitutions in the target enzyme Erg11p of azole antifungals contribute to clinically-relevant azole resistance in Candida albicans. A simple molecular method for rapid detection of ERG11 gene mutations would be an advantage as a screening tool to identify potentially-resistant strains and to track their movement. To complement DNA sequencing, we developed a padlock probe and rolling circle amplification (RCA)-based method to detect a series of mutations in th...

Analysis of the ergosterol biosynthesis pathway cloning, molecular characterization and phylogeny of lanosterol 14α-demethylase (ERG11 gene of Moniliophthora perniciosa

Directory of Open Access Journals (Sweden)

Geruza de Oliveira Ceita

2014-12-01

Full Text Available The phytopathogenic fungus Moniliophthora perniciosa (Stahel Aime & Philips-Mora, causal agent of witches' broom disease of cocoa, causes countless damage to cocoa production in Brazil. Molecular studies have attempted to identify genes that play important roles in fungal survival and virulence. In this study, sequences deposited in the M. perniciosa Genome Sequencing Project database were analyzed to identify potential biological targets. For the first time, the ergosterol biosynthetic pathway in M. perniciosa was studied and the lanosterol 14α-demethylase gene (ERG11 that encodes the main enzyme of this pathway and is a target for fungicides was cloned, characterized molecularly and its phylogeny analyzed. ERG11 genomic DNA and cDNA were characterized and sequence analysis of the ERG11 protein identified highly conserved domains typical of this enzyme, such as SRS1, SRS4, EXXR and the heme-binding region (HBR. Comparison of the protein sequences and phylogenetic analysis revealed that the M. perniciosa enzyme was most closely related to that of Coprinopsis cinerea.

An NMR investigation of the structure, function and role of the hERG channel selectivity filter in the long QT syndrome.

Science.gov (United States)

Gravel, Andrée E; Arnold, Alexandre A; Dufourc, Erick J; Marcotte, Isabelle

2013-06-01

The human ether-a-go-go-related gene (hERG) voltage-gated K(+) channels are located in heart cell membranes and hold a unique selectivity filter (SF) amino acid sequence (SVGFG) as compared to other K(+) channels (TVGYG). The hERG provokes the acquired long QT syndrome (ALQTS) when blocked, as a side effect of drugs, leading to arrhythmia or heart failure. Its pore domain - including the SF - is believed to be a cardiotoxic drug target. In this study combining solution and solid-state NMR experiments we examine the structure and function of hERG's L(622)-K(638) segment which comprises the SF, as well as its role in the ALQTS using reported active drugs. We first show that the SF segment is unstructured in solution with and without K(+) ions in its surroundings, consistent with the expected flexibility required for the change between the different channel conductive states predicted by computational studies. We also show that the SF segment has the potential to perturb the membrane, but that the presence of K(+) ions cancels this interaction. The SF moiety appears to be a possible target for promethazine in the ALQTS mechanism, but not as much for bepridil, cetirizine, diphenhydramine and fluvoxamine. The membrane affinity of the SF is also affected by the presence of drugs which also perturb model DMPC-based membranes. These results thus suggest that the membrane could play a role in the ALQTS by promoting the access to transmembrane or intracellular targets on the hERG channel, or perturbing the lipid-protein synergy. Copyright © 2013 Elsevier B.V. All rights reserved.

PASS Reference Set Application: Lin UW (2010) TMPRSS2-ERG-PCA-PASS — EDRN Public Portal

Science.gov (United States)

Active surveillance is used to manage low-risk prostate cancer. Both PCA3 and TMPRSS2:ERG are promising biomarkers that may be associated with aggressive disease. This study examines the correlation of these biomarkers with higher cancer volume and grade determined at the time of biopsy in an active surveillance cohort.

Realization of chiral symmetry in the ERG

International Nuclear Information System (INIS)

Echigo, Yoshio; Igarashi, Yuji

2011-01-01

We discuss within the framework of the ERG how chiral symmetry is realized in a linear σ model. A generalized Ginsparg-Wilson relation is obtained from the Ward-Takahashi identities for the Wilson action assumed to be bilinear in the Dirac fields. We construct a family of its non-perturbative solutions. The family generates the most general solutions to the Ward-Takahashi identities. Some special solutions are discussed. For each solution in this family, chiral symmetry is realized in such a way that a change in the Wilson action under non-linear symmetry transformation is canceled with a change in the functional measure. We discuss that the family of solutions reduces via a field redefinition to a family of the Wilson actions with some composite object of the scalar fields which has a simple transformation property. For this family, chiral symmetry is linearly realized with a continuum analog of the operator extension of γ 5 used on the lattice. We also show that there exist some appropriate Dirac fields which obey the standard chiral transformations with γ 5 in contrast to the lattice case. Their Yukawa interaction with scalars, however, becomes non-linear. (author)

The ARASE (ERG) magnetic field investigation

Science.gov (United States)

Matsuoka, Ayako; Teramoto, Mariko; Nomura, Reiko; Nosé, Masahito; Fujimoto, Akiko; Tanaka, Yoshimasa; Shinohara, Manabu; Nagatsuma, Tsutomu; Shiokawa, Kazuo; Obana, Yuki; Miyoshi, Yoshizumi; Mita, Makoto; Takashima, Takeshi; Shinohara, Iku

2018-03-01

The fluxgate magnetometer for the Arase (ERG) spacecraft mission was built to investigate particle acceleration processes in the inner magnetosphere. Precise measurements of the field intensity and direction are essential in studying the motion of particles, the properties of waves interacting with the particles, and magnetic field variations induced by electric currents. By observing temporal field variations, we will more deeply understand magnetohydrodynamic and electromagnetic ion-cyclotron waves in the ultra-low-frequency range, which can cause production and loss of relativistic electrons and ring-current particles. The hardware and software designs of the Magnetic Field Experiment (MGF) were optimized to meet the requirements for studying these phenomena. The MGF makes measurements at a sampling rate of 256 vectors/s, and the data are averaged onboard to fit the telemetry budget. The magnetometer switches the dynamic range between ± 8000 and ± 60,000 nT, depending on the local magnetic field intensity. The experiment is calibrated by preflight tests and through analysis of in-orbit data. MGF data are edited into files with a common data file format, archived on a data server, and made available to the science community. Magnetic field observation by the MGF will significantly improve our knowledge of the growth and decay of radiation belts and ring currents, as well as the dynamics of geospace storms.

Changes in cortical cytoskeletal and extracellular matrix gene expression in prostate cancer are related to oncogenic ERG deregulation

International Nuclear Information System (INIS)

Schulz, Wolfgang A; Ingenwerth, Marc; Djuidje, Carolle E; Hader, Christiane; Rahnenführer, Jörg; Engers, Rainer

2010-01-01

The cortical cytoskeleton network connects the actin cytoskeleton to various membrane proteins, influencing cell adhesion, polarity, migration and response to extracellular signals. Previous studies have suggested changes in the expression of specific components in prostate cancer, especially of 4.1 proteins (encoded by EPB41 genes) which form nodes in this network. Expression of EPB41L1, EPB41L2, EPB41L3 (protein: 4.1B), EPB41L4B (EHM2), EPB41L5, EPB49 (dematin), VIL2 (ezrin), and DLG1 (summarized as „cortical cytoskeleton' genes) as well as ERG was measured by quantitative RT-PCR in a well-characterized set of 45 M0 prostate adenocarcinoma and 13 benign tissues. Hypermethylation of EPB41L3 and GSTP1 was compared in 93 cancer tissues by methylation-specific PCR. Expression of 4.1B was further studied by immunohistochemistry. EPB41L1 and EPB41L3 were significantly downregulated and EPB41L4B was upregulated in cancer tissues. Low EPB41L1 or high EPB41L4B expression were associated with earlier biochemical recurrence. None of the other cortical cytoskeleton genes displayed expression changes, in particular EPB49 and VIL2, despite hints from previous studies. EPB41L3 downregulation was significantly associated with hypermethylation of its promoter and strongly correlated with GSTP1 hypermethylation. Protein 4.1B was detected most strongly in the basal cells of normal prostate epithelia. Its expression in carcinoma cells was similar to the weaker one in normal luminal cells. EPB41L3 downregulation and EPB41L4B upregulation were essentially restricted to the 22 cases with ERG overexpression. Expression changes in EPB41L3 and EPB41L4B closely paralleled those previously observed for the extracellular matrix genes FBLN1 and SPOCK1, respectively. Specific changes in the cortical cytoskeleton were observed during prostate cancer progression. They parallel changes in the expression of extracellular matrix components and all together appear to be associated with

SPINK1 Overexpression in Localized Prostate Cancer: a Rare Event Inversely Associated with ERG Expression and Exclusive of Homozygous PTEN Deletion.

Science.gov (United States)

Huang, Kuo-Cheng; Evans, Andrew; Donnelly, Bryan; Bismar, Tarek A

2017-04-01

SPINK1 is proposed as potential prognostic marker in prostate cancer (PCA). However, its relation to PTEN and ERG in localized PCA remains unclear. The study population consisted of two independent cohorts of men treated by radical prostatectomy for localized PCA (discovery n = 218 and validation n = 129). Patterns of association between SPINK1 and each of ERG and PTEN were evaluated by immunohistochemistry and fluorescence in situ hybridization. Associations between SPINK1 expression and various pathologic parameters and clinical outcome were also investigated. SPINK1 was expressed in 15.3 % and 10.9 % of cases in the discovery and validation cohort, respectively. SPINK expression was observed in 5.56 % of high-grade prostatic intraepithelial neoplasia and 1.1 % of adjacent morphologically benign prostatic glands. SPINK1 and ERG expression were almost exclusive, with only 1.0 % of the cases co-expressing both in the same core sample. SPINK1 interfocal and within-core heterogeneity was noted in 29.2 % and 64.6 % of cases, respectively. SPINK1 expression was not significantly associated with PTEN deletion in the two cohorts (p = 0.871 for discovery cohort and p = 0.293 for validation cohort). While SPINK1 expression did occur with hemizygous PTEN deletion, there was a complete absence of SPINK1 expression in PCA showing homozygous PTEN deletion, which was confirmed in the validation cohort (p = 0.02). Despite SPINK1's association with higher Gleason score (>7) (p = 0.02), it was not associated with other pathological parameters or biochemical recurrence post-radical prostatectomy. We documented absolute exclusivity between SPINK1 overexpression and homozygous PTEN deletion in localized PCA. SPINK1 and ERG expressions are exclusive events in PCA. SPINK1 is not of added prognostic value in localized PCA.

ELECTROOCULOGRAPHY AND PATTERN ERG IN THE DIAGNOSTICS OF BEST’S VITELLIFORM DISTROPHY

Directory of Open Access Journals (Sweden)

Martina Jarc-Vidmar

2002-12-01

Full Text Available Background. The aim of the study was to develop electrooculography in accordance with ISCEV standards and to test its accuracy in the diagnosis of Best’s disease, where the EOG results should be invariably abnormal in all affected members. The pathophysiology of Best’s disease is not yet completely understood, so pattern and full field flash ERG responses compared to visual acuity and stage of the disease were used to asses the neurosensory retinal function in different stages of Best’s disease.Patients and methods. The EOG was recorded in accordance with ISCEV standards on 30 healthy individuals to determine normal values of our laboratory. Pattern as well as photopic and scotopic ERG were recorded on 24 eyes of 12 patients with typical Best’s disease with abnormal EOG responses. The results were compared to visual acuity and stage of the disease.Results. Our EOG normative data are comparable with results from other laboratories: the mean value of Arden ratio is 2.32, the range of 2 standard deviations from the mean value is from 1.6 to 3.04. The patients with Best’s disease have statisticaly significant lower values of Arden ratio (the mean value beeing 1.19. 12 patients (24 eyes with Best’s disease with abnormal EOG values were divided in two groups according to visual acuity. In the first group of 12 eyes with visual acuity > 0.5 PERG P50 and N95 responses were all in the normal range. In the second group of 12 eyes with visual acuity 0.5 or less PERG showed reduced both P50 and N95 responses in 5 eyes, and N95 solely, in two eyes.The photopic and scotopic electroretinographic responses were normal in all patients. Progression of the disease, seen in the deterioration of visual acuity, corresponded well with reduction of both PERG P50 and N95 responses. There was no correlation found between visual acuity and EOG responses.Conclusions. In the study on patients with Best’s disease, it was confirmed that EOG is a very sensitive

Adubação mineral e orgânica e a densidade populacional de Thrips tabaci Lind. (Thysanoptera: Thripidae em cebola Mineral and organic fertilization and onion thrips, Thrips tabaci Lind. (Thysanoptera: Thripidae population density

Directory of Open Access Journals (Sweden)

Paulo Antonio de Souza Gonçalves

2004-08-01

Full Text Available O efeito da adubação mineral e orgânica sobre a densidade populacional de Thrips tabaci Lind. em cebola, Allium cepa L., foi avaliado na Estação Experimental de Ituporanga, SC (Empresa de Pesquisa Agropecuária e Extensão Rural de Santa Catarina, entre agosto e dezembro de 1998. Os tratamentos foram níveis de adubação mineral com N, P2O5 e K2O em dose recomendada e três vezes a recomendada, adubação orgânica e a testemunha foi a ausência de adubação. Os tratamentos foram as seguintes doses de nutrientes: 1 30 + 120 + 60kg ha-1 de NPK; 2 90 + 360 + 180kg ha-1 de NPK; 3 75kg ha-1 de N; 4 225kg ha-1 de N; 5 80kg ha-1 de P2O5; 6 240kg ha-1 de P2O5; 7 60kg ha-1 de K2O; 8 180kg ha-1 de K2O; 9 75kg ha-1 de N + 80kg ha-1 de P2O5 (esterco de suíno + fosfato natural; 10 225kg ha-1 de N + 240kg ha-1 de P2O5 (esterco de suíno + fosfato natural; 11 37,5kg ha-1 de N + 40kg ha-1 de P2O5 (esterco de suíno + fosfato natural; testemunha sem adubação. Nenhuma das fontes e níveis de adubação apresentaram nível populacional de T. tabaci superior à testemunha sem adubo.The effect of the mineral and organic fertilization on onion thrips, Thrips tabaci Lind., population density was evaluated at Ituporanga Experiment Station, EPAGRI, Santa Catarina State, Brazil, between August and December 1998. The treatments were different levels of mineral fertilization with N, P2O5 and K2O at recommended rate and three times recommended rate, the organic fertilization and without fertilization was check. The treatments in nutrient rate were: 30 + 120 + 60kg NPK ha-1; 90 + 360 + 180kg NPK ha-1; 75kg N ha-1; 225kg N ha-1; 80kg P2O5 ha-1; 240kg P2O5 ha-1; 60kg K2O ha-1; 180kg K2O ha-1; 75kg N ha-1 + 80kg P2O5 ha-1 (swine manure + phosphate rock; 225kg N + 240kg P2O5 ha-1 (swine manure + phosphate rock; 37,5kg N + 40kg P2O5 ha-1 (swine manure + phosphate rock; check without fertilizer. The onion thrips population density was similar among treatments with

Use of temporal immersion systems for the in vitro multiplication of Anthurium andraeanum Lind. var. Lambada shoots

Directory of Open Access Journals (Sweden)

Nydia del Rivero Bautista

2004-04-01

Full Text Available Two methods to improve the efficiency in the multiplication of shoots of Anthurium andraeanum Lind., they were used to optimize the frequencies of immersion of the explants using a System of Temporary Immersion. The relative efficiency of the method conventional means of culture semisolid for the multiplication of shoots was compared with the method of System of Temporary Immersion. The highest rate of multiplication of shoots was reached using six immersions four times a day during two minutes, controlling the immersion cycles achieves plants better developed and bigger multiplication coefficient. The plantlets multiplied through this method were harvested with 2 to 3 cm of longitude containing from two to five leaves after a period of culture of 50 days. The formation of callus, hiperhidricity and other abnormalities were not observed during the process. The plants obtained by this method were taken to rooting in medium of culture semisólid. This system avoids risks of contamination, it increases yields, it reduces manpower costs and of containers. This technique for its relationship benefit-cost has significant implications for the commercial propagation of the Anthurium. Key words: Culture medium, multiplication rate, plantlets.

Ultrastructural and ERG findings in progressive rod-cone dystrophy in a litter of Labrador retrievers.

Science.gov (United States)

Raitta, C; Kommonen, B; Ulshafer, R; Karhunen, U

1991-02-01

Early ultrastructural findings of a progressive photoreceptor dystrophy and corresponding ERG findings are reported in 3 Labrador Retrievers from a litter of 7 pups bred from 2 dogs clinically and electroretinographically affected with generalized progressive retinal dystrophy. The pups were euthanized at 5, 11 and 15 months post partum. The most prominent ultrastructural finding was photoreceptor dystrophy. At 5 months the outer nuclear layer (ONL) consisted of 8-10 layers and seemed reduced in thickness, pyknotic nuclei were seen in this layer. The receptor outer segments (OS) were short and swollen. Some disorientation of OS discs occurred. In the 11-months specimen 7-8 ONL layers were identified. Overall thinning of the neuro-retina had occurred and fewer receptors compared to the 5-months specimen were present. By 15 months the ONL was further reduced to about 4 layers. Enlarged internuclear spaces were present in the ONL as well as around inner segments (IS). Phagocytic cells were frequent among remains of OS. The pigment epithelium appeared normal. The dark adapted ERG b-wave amplitudes and photopic 30 Hz flicker responses were low in comparison to controls of the same breed, and decreased with age. The condition represents a progressive rod-cone dystrophy which shares similarities with primary receptor dystrophy in man such as retinitis pigmentosa.

Thermal behavior and ice-table depth within the north polar erg of Mars

Science.gov (United States)

Putzig, Nathaniel E.; Mellon, Michael T.; Herkenhoff, Kenneth E.; Phillips, Roger J.; Davis, Brian J.; Ewer, Kenneth J.; Bowers, Lauren M.

2014-01-01

We fully resolve a long-standing thermal discrepancy concerning the north polar erg of Mars. Several recent studies have shown that the erg’s thermal properties are consistent with normal basaltic sand overlying shallow ground ice or ice-cemented sand. Our findings bolster that conclusion by thoroughly characterizing the thermal behavior of the erg, demonstrating that other likely forms of physical heterogeneity play only a minor role, and obviating the need to invoke exotic materials. Thermal inertia as calculated from orbital temperature observations of the dunes has previously been found to be more consistent with dust-sized materials than with sand. Since theory and laboratory data show that dunes will only form out of sand-sized particles, exotic sand-sized agglomerations of dust have been invoked to explain the low values of thermal inertia. However, the polar dunes exhibit the same darker appearance and color as that of dunes found elsewhere on the planet that have thermal inertia consistent with normal sand-sized basaltic grains, whereas Martian dust deposits are generally lighter and redder. The alternative explanation for the discrepancy as a thermal effect of a shallow ice table is supported by our analysis of observations from the Mars Global Surveyor Thermal Emission Spectrometer and the Mars Odyssey Thermal Emission Imaging System and by forward modeling of physical heterogeneity. In addition, our results exclude a uniform composition of dark dust-sized materials, and they show that the thermal effects of the dune slopes and bright interdune materials evident in high-resolution images cannot account for the erg’s thermal behavior.

Computational analysis of the effects of the hERG channel opener NS1643 in a human ventricular cell model

DEFF Research Database (Denmark)

Peitersen, Torben; Grunnet, Morten; Benson, Alan P

2008-01-01

BACKGROUND: Dysfunction or pharmacologic inhibition of repolarizing cardiac ionic currents can lead to fatal arrhythmias. The hERG potassium channel underlies the repolarizing current I(Kr), and mutations therein can produce both long and short QT syndromes (LQT2 and SQT1). We previously reported...

The Plasma Wave Experiment (PWE) on board the Arase (ERG) satellite

Science.gov (United States)

Kasahara, Yoshiya; Kasaba, Yasumasa; Kojima, Hirotsugu; Yagitani, Satoshi; Ishisaka, Keigo; Kumamoto, Atsushi; Tsuchiya, Fuminori; Ozaki, Mitsunori; Matsuda, Shoya; Imachi, Tomohiko; Miyoshi, Yoshizumi; Hikishima, Mitsuru; Katoh, Yuto; Ota, Mamoru; Shoji, Masafumi; Matsuoka, Ayako; Shinohara, Iku

2018-05-01

The Exploration of energization and Radiation in Geospace (ERG) project aims to study acceleration and loss mechanisms of relativistic electrons around the Earth. The Arase (ERG) satellite was launched on December 20, 2016, to explore in the heart of the Earth's radiation belt. In the present paper, we introduce the specifications of the Plasma Wave Experiment (PWE) on board the Arase satellite. In the inner magnetosphere, plasma waves, such as the whistler-mode chorus, electromagnetic ion cyclotron wave, and magnetosonic wave, are expected to interact with particles over a wide energy range and contribute to high-energy particle loss and/or acceleration processes. Thermal plasma density is another key parameter because it controls the dispersion relation of plasma waves, which affects wave-particle interaction conditions and wave propagation characteristics. The DC electric field also plays an important role in controlling the global dynamics of the inner magnetosphere. The PWE, which consists of an orthogonal electric field sensor (WPT; wire probe antenna), a triaxial magnetic sensor (MSC; magnetic search coil), and receivers named electric field detector (EFD), waveform capture and onboard frequency analyzer (WFC/OFA), and high-frequency analyzer (HFA), was developed to measure the DC electric field and plasma waves in the inner magnetosphere. Using these sensors and receivers, the PWE covers a wide frequency range from DC to 10 MHz for electric fields and from a few Hz to 100 kHz for magnetic fields. We produce continuous ELF/VLF/HF range wave spectra and ELF range waveforms for 24 h each day. We also produce spectral matrices as continuous data for wave direction finding. In addition, we intermittently produce two types of waveform burst data, "chorus burst" and "EMIC burst." We also input raw waveform data into the software-type wave-particle interaction analyzer (S-WPIA), which derives direct correlation between waves and particles. Finally, we introduce our

Electroretinogram (ERG) to photic stimuli should be carefully distinct from photic brainstem reflex in patients with deep coma.

Science.gov (United States)

Mitsuhashi, Masahiro; Hitomi, Takefumi; Aoyama, Akihiro; Kaido, Toshimi; Ikeda, Akio; Takahashi, Ryosuke

2017-08-31

Patient 1: A 35-year-old woman became deep coma because of intracranial hemorrhage after pulmonary surgery. Patient 2: A 39-year-old woman became deep coma because of cerebellar hemorrhage after hepatic surgery. Scalp-recorded digital electroencephalography (EEG) showed electrocerebral inactivity in both cases. In addition, both EEG showed repetitive discharges at bilateral frontopolar electrodes in response to photic stimuli. The amplitude and latency of the discharges was 17 μV and 24 msec in case 1, and 9 μV and 27 msec in case 2 respectively. The activity at left frontopolar electrode disappeared after coverage of the ipsilateral eye. Based on these findings, we could exclude the possibility of brainstem response and judged it as electroretinogram (ERG). Photic stimulation is a useful activation method in EEG recording, and we can also evaluate brainstem function by checking photic blink reflex if it is evoked. However, we should be cautious about the distinction of ERG from photic blink reflex when brain death is clinically suspected.

Origin of the Sinai-Negev erg, Egypt and Israel: mineralogical and geochemical evidence for the importance of the Nile and sea level history

Science.gov (United States)

Muhs, Daniel R.; Roskin, Joel; Tsoar, Haim; Skipp, Gary; Budahn, James R.; Sneh, Amihai; Porat, Naomi; Stanley, Jean-Daniel; Katra, Itzhak; Blumberg, Dan G.

2013-01-01

The Sinai–Negev erg occupies an area of 13,000 km2 in the deserts of Egypt and Israel. Aeolian sand of this erg has been proposed to be derived from the Nile Delta, but empirical data supporting this view are lacking. An alternative source sediment is sand from the large Wadi El Arish drainage system in central and northern Sinai. Mineralogy of the Negev and Sinai dunes shows that they are high in quartz, with much smaller amounts of K-feldspar and plagioclase. Both Nile Delta sands and Sinai wadi sands, upstream of the dunes, also have high amounts of quartz relative to K-feldspar and plagioclase. However, Sinai wadi sands have abundant calcite, whereas Nile Delta sands have little or no calcite. Overall, the mineralogical data suggest that the dunes are derived dominantly from the Nile Delta, with Sinai wadi sands being a minor contributor. Geochemical data that proxy for both the light mineral fraction (SiO2/10–Al2O3 + Na2O + K2O–CaO) and heavy mineral fraction (Fe2O3–MgO–TiO2) also indicate a dominant Nile Delta source for the dunes. Thus, we report here the first empirical evidence that the Sinai–Negev dunes are derived dominantly from the Nile Delta. Linkage of the Sinai–Negev erg to the Nile Delta as a source is consistent with the distribution of OSL ages of Negev dunes in recent studies. Stratigraphic studies show that during the Last Glacial period, when dune incursions in the Sinai–Negev erg began, what is now the Nile Delta area was characterized by a broad, sandy, minimally vegetated plain, with seasonally dry anastomosing channels. Such conditions were ideal for providing a ready source of sand for aeolian transport under what were probably much stronger glacial-age winds. With the post-glacial rise in sea level, the Nile River began to aggrade. Post-glacial sedimentation has been dominated by fine-grained silts and clays. Thus, sea level, along with favorable climatic conditions, emerges as a major influence on the timing of dune

ERG [Engineering Review Group] and GRG [Geologic Review Group] review of the horizontal versus vertical modes of waste emplacement at the Deaf Smith County site, Texas

International Nuclear Information System (INIS)

Chytrowski, B.R.

1988-01-01

The Engineering Review Group (ERG) and Geologic Review Group (GRG) were established by the Office of Nuclear Waste Isolation (ONWI) to help evaluate specific issues in the US Department of Energy's nuclear waste repository program. The December 1985 meeting and the February 1986 meeting dealt with the evaluation of the Fluor Technology, Inc., architect-engineer recommendation of the horizontal mode of waste package emplacement for the Site Characterization Plan Conceptual Design Report (SCP-CDR). The ONWI recommendation regarding horizontal and vertical modes of waste package emplacement and associated studies was reviewed. This report documents the ERG and GRG's comments and recommendations on this subject and ONWI responses to the specific points raised by these groups. The ERG and GRG joint review groups concurred with ONWI recommendations that additional studies are required in order to reach a decision on the method of emplacement to be used. In the opinion of these groups, both methods can be implemented; however, should the decision be reached today the vertical mode would be preferred

Fluorescence-tracking of activation gating in human ERG channels reveals rapid S4 movement and slow pore opening.

Directory of Open Access Journals (Sweden)

Zeineb Es-Salah-Lamoureux

2010-05-01

Full Text Available hERG channels are physiologically important ion channels which mediate cardiac repolarization as a result of their unusual gating properties. These are very slow activation compared with other mammalian voltage-gated potassium channels, and extremely rapid inactivation. The mechanism of slow activation is not well understood and is investigated here using fluorescence as a direct measure of S4 movement and pore opening.Tetramethylrhodamine-5-maleimide (TMRM fluorescence at E519 has been used to track S4 voltage sensor movement, and channel opening and closing in hERG channels. Endogenous cysteines (C445 and C449 in the S1-S2 linker bound TMRM, which caused a 10 mV hyperpolarization of the V((1/2 of activation to -27.5+/-2.0 mV, and showed voltage-dependent fluorescence signals. Substitution of S1-S2 linker cysteines with valines allowed unobstructed recording of S3-S4 linker E519C and L520C emission signals. Depolarization of E519C channels caused rapid initial fluorescence quenching, fit with a double Boltzmann relationship, F-V(ON, with V((1/2 (,1 = -37.8+/-1.7 mV, and V((1/2 (,2 = 43.5+/-7.9 mV. The first phase, V((1/2 (,1, was approximately 20 mV negative to the conductance-voltage relationship measured from ionic tail currents (G-V((1/2 = -18.3+/-1.2 mV, and relatively unchanged in a non-inactivating E519C:S620T mutant (V((1/2 = -34.4+/-1.5 mV, suggesting the fast initial fluorescence quenching tracked S4 voltage sensor movement. The second phase of rapid quenching was absent in the S620T mutant. The E519C fluorescence upon repolarization (V((1/2 = -20.6+/-1.2, k = 11.4 mV and L520C quenching during depolarization (V((1/2 = -26.8+/-1.0, k = 13.3 mV matched the respective voltage dependencies of hERG ionic tails, and deactivation time constants from -40 to -110 mV, suggesting they detected pore-S4 rearrangements related to ionic current flow during pore opening and closing.THE DATA INDICATE: 1 that rapid environmental changes occur at the

The prognostic value of SUMO1/Sentrin specific peptidase 1 (SENP1) in prostate cancer is limited to ERG-fusion positive tumors lacking PTEN deletion

International Nuclear Information System (INIS)

Burdelski, Christoph; Menan, Devi; Tsourlakis, Maria Christina; Kluth, Martina; Hube-Magg, Claudia; Melling, Nathaniel; Minner, Sarah; Koop, Christina; Graefen, Markus; Heinzer, Hans; Wittmer, Corinna; Sauter, Guido; Simon, Ronald; Schlomm, Thorsten; Steurer, Stefan; Krech, Till

2015-01-01

Posttranscriptional protein modification by SUMOylation plays an important role in tumor development and progression. In the current study we analyzed prevalence and prognostic impact of the de-SUMOylation enzyme SENP1 in prostate cancer. SENP1 expression was analyzed by immunohistochemistry on a tissue microarray containing more than 12,400 prostate cancer specimens. Results were compared to tumor phenotype, ERG status, genomic deletions of 3p, 5q, 6q and PTEN, and biochemical recurrence. SENP1 immunostaining was detectable in 34.5 % of 9,516 interpretable cancers and considered strong in 7.3 %, moderate in 14.9 % and weak in 12.3 % of cases. Strong SENP1 expression was linked to advanced pT stage (p < 0.0001), high Gleason grade (p < 0.0001), positive lymph node status (p = 0.0019), high pre-operative PSA levels (p = 0.0037), and PSA recurrence (p < 0.0001). SENP1 expression was strongly associated with positive ERG fusion status as determined by both in situ hybridization (FISH) and immunohistochemistry as well as with PTEN deletions. Detectable SENP1 immunostaining was found in 41 % of ERG positive and in 47 % of PTEN deleted cancers but in only 30 % of ERG negative and 30 % of PTEN non-deleted cancers (p < 0.0001 each). Deletions of 3p, 5q, and 6q were unrelated to SENP1 expression. Subset analyses revealed that the prognostic impact of SENP1 expression was solely driven by the subgroup of ERG positive, PTEN undeleted cancers. In this subgroup, the prognostic role of SENP1 expression was independent of the preoperative PSA level, tumor stage, Gleason grade, and the status of the resection margin. SENP1 expression has strong prognostic impact in a molecularly defined subset of cancers. This is per se not surprising as the biologic impact of each individual molecular event is likely to be dependent on its cellular environment. However, such findings challenge the concept of finding clinically relevant molecular signatures that are equally applicable to all

Crystallographic and magnetic structure of the novel compound ErGe 1.83

Science.gov (United States)

Oleksyn, O.; Schobinger-Papamantellos, P.; Ritter, C.; de Groot, C. H.; Buschow, K. H. J.

1997-02-01

The crystal structure and the magnetic ordering of the novel orthorhombic compound ErGe 2-x has been studied by neutron powder diffraction and magnetic measurements. The crystal structure belongs to the DyGe 1.85-type (space group Cmc2 1)·ErGe 2-x ( x = 0.17 (2)) orders antiferromagnetically below TN = 6 K and displays a metamagnetic behaviour. The magnetic cell has the same size as the chemical unit cell ( q = 0 ). The magnetic space group is Cmc2 1 (Sh 36173). At T = 1.5 K the magnetic moments of the two erbium sites have the same ordered magnetic moment values of 7.63 (6) μB/Er and are antiferromagnetically coupled leading to an uniaxial structure along the a direction.

Biophysical characterization of the short QT mutation hERG-N588K reveals a mixed gain-and loss-of-function

DEFF Research Database (Denmark)

Grunnet, M.; Diness, T.G.; Hansen, R.S.

2008-01-01

The short QT syndrome is a newly discovered pro-arrhythmic condition, which may cause ventricular fibrillation and sudden death. Short QT can originate from the apparent gain-of-function mutation N588K in the hERG potassium channel that conducts repolarising I(Kr) current. The present study...

Cone dystrophy with "supernormal" rod ERG: psychophysical testing shows comparable rod and cone temporal sensitivity losses with no gain in rod function.

Science.gov (United States)

Stockman, Andrew; Henning, G Bruce; Michaelides, Michel; Moore, Anthony T; Webster, Andrew R; Cammack, Jocelyn; Ripamonti, Caterina

2014-02-10

We report a psychophysical investigation of 5 observers with the retinal disorder "cone dystrophy with supernormal rod ERG," caused by mutations in the gene KCNV2 that encodes a voltage-gated potassium channel found in rod and cone photoreceptors. We compared losses for rod- and for cone-mediated vision to further investigate the disorder and to assess whether the supernormal ERG is associated with any visual benefit. L-cone, S-cone, and rod temporal acuity (critical flicker fusion frequency) were measured as a function of target irradiance; L-cone temporal contrast sensitivity was measured as a function of temporal frequency. Temporal acuity measures revealed that losses for vision mediated by rods, S-cones, and L-cones are roughly equivalent. Further, the gain in rod function implied by the supernormal ERG provides no apparent benefit to near-threshold rod-mediated visual performance. The L-cone temporal contrast sensitivity function in affected observers was similar in shape to the mean normal function but only after the mean function was compressed by halving the logarithmic sensitivities. The name of this disorder is potentially misleading because the comparable losses found across rod and cone vision suggest that the disorder is a generalized cone-rod dystrophy. Temporal acuity and temporal contrast sensitivity measures are broadly consistent with the defect in the voltage-gated potassium channel producing a nonlinear distortion of the photoreceptor response but after otherwise normal transduction processes.

The N-terminal tail of hERG contains an amphipathic α-helix that regulates channel deactivation.

Directory of Open Access Journals (Sweden)

Chai Ann Ng

Full Text Available The cytoplasmic N-terminal domain of the human ether-a-go-go related gene (hERG K+ channel is critical for the slow deactivation kinetics of the channel. However, the mechanism(s by which the N-terminal domain regulates deactivation remains to be determined. Here we show that the solution NMR structure of the N-terminal 135 residues of hERG contains a previously described Per-Arnt-Sim (PAS domain (residues 26-135 as well as an amphipathic α-helix (residues 13-23 and an initial unstructured segment (residues 2-9. Deletion of residues 2-25, only the unstructured segment (residues 2-9 or replacement of the α-helix with a flexible linker all result in enhanced rates of deactivation. Thus, both the initial flexible segment and the α-helix are required but neither is sufficient to confer slow deactivation kinetics. Alanine scanning mutagenesis identified R5 and G6 in the initial flexible segment as critical for slow deactivation. Alanine mutants in the helical region had less dramatic phenotypes. We propose that the PAS domain is bound close to the central core of the channel and that the N-terminal α-helix ensures that the flexible tail is correctly orientated for interaction with the activation gating machinery to stabilize the open state of the channel.

ZO-1 expression is suppressed by GM-CSF via miR-96/ERG in brain microvascular endothelial cells.

Science.gov (United States)

Zhang, Hu; Zhang, Shuhong; Zhang, Jilin; Liu, Dongxin; Wei, Jiayi; Fang, Wengang; Zhao, Weidong; Chen, Yuhua; Shang, Deshu

2018-05-01

The level of granulocyte-macrophage colony-stimulating factor (GM-CSF) increases in some disorders such as vascular dementia, Alzheimer's disease, and multiple sclerosis. We previously reported that in Alzheimer's disease patients, a high level of GM-CSF in the brain parenchyma downregulated expression of ZO-1, a blood-brain barrier tight junction protein, and facilitated the infiltration of peripheral monocytes across the blood-brain barrier. However, the molecular mechanism underlying regulation of ZO-1 expression by GM-CSF is unclear. Herein, we found that the erythroblast transformation-specific (ETS) transcription factor ERG cooperated with the proto-oncogene protein c-MYC in regulation of ZO-1 transcription in brain microvascular endothelial cells (BMECs). The ERG expression was suppressed by miR-96 which was increased by GM-CSF through the phosphoinositide-3 kinase (PI3K)/Akt pathway. Inhibition of miR-96 prevented ZO-1 down-regulation induced by GM-CSF both in vitro and in vivo. Our results revealed the mechanism of ZO-1 expression reduced by GM-CSF, and provided a potential target, miR-96, which could block ZO-1 down-regulation caused by GM-CSF in BMECs.

Engineering Review Group (ERG) and Geologic Review Group (GRG) report on brine migration at the Deaf Smith County site salt repository horizon

International Nuclear Information System (INIS)

1986-01-01

In April 1986, ONWI requested the ERG and GRG to jointly address the status of current knowledge of, and ONWI approach to further characterization of, the geohydrology of the candidate repository horizon of the potential site in Deaf Smith County, Texas. Specifically, the ERG-GRG was asked to evaluate the status of understanding of the hydrogeology of the Lower San Andres Unit 4 (LSA-4) evaporite section and identify any major gaps in the data; evaluate the current understanding of the chemistry and movement of brines in the LSA-4 salt and associated interbeds; develop recommendations for estimating the upper limit quantity of brines, and modeling the brine movement, with respect to the emplaced HLW packages; and identify questions concerning the chemistry of the brines and recommend a technical approach to addressing these questions. 19 refs

keV-Scale sterile neutrino sensitivity estimation with time-of-flight spectroscopy in KATRIN using self-consistent approximate Monte Carlo

Science.gov (United States)

Steinbrink, Nicholas M. N.; Behrens, Jan D.; Mertens, Susanne; Ranitzsch, Philipp C.-O.; Weinheimer, Christian

2018-03-01

We investigate the sensitivity of the Karlsruhe Tritium Neutrino Experiment (KATRIN) to keV-scale sterile neutrinos, which are promising dark matter candidates. Since the active-sterile mixing would lead to a second component in the tritium β-spectrum with a weak relative intensity of order sin ^2θ ≲ 10^{-6}, additional experimental strategies are required to extract this small signature and to eliminate systematics. A possible strategy is to run the experiment in an alternative time-of-flight (TOF) mode, yielding differential TOF spectra in contrast to the integrating standard mode. In order to estimate the sensitivity from a reduced sample size, a new analysis method, called self-consistent approximate Monte Carlo (SCAMC), has been developed. The simulations show that an ideal TOF mode would be able to achieve a statistical sensitivity of sin ^2θ ˜ 5 × 10^{-9} at one σ , improving the standard mode by approximately a factor two. This relative benefit grows significantly if additional exemplary systematics are considered. A possible implementation of the TOF mode with existing hardware, called gated filtering, is investigated, which, however, comes at the price of a reduced average signal rate.

Comparative evaluation of urinary PCA3 and TMPRSS2: ERG scores and serum PHI in predicting prostate cancer aggressiveness.

Science.gov (United States)

Tallon, Lucile; Luangphakdy, Devillier; Ruffion, Alain; Colombel, Marc; Devonec, Marian; Champetier, Denis; Paparel, Philippe; Decaussin-Petrucci, Myriam; Perrin, Paul; Vlaeminck-Guillem, Virginie

2014-07-30

It has been suggested that urinary PCA3 and TMPRSS2:ERG fusion tests and serum PHI correlate to cancer aggressiveness-related pathological criteria at prostatectomy. To evaluate and compare their ability in predicting prostate cancer aggressiveness, PHI and urinary PCA3 and TMPRSS2:ERG (T2) scores were assessed in 154 patients who underwent radical prostatectomy for biopsy-proven prostate cancer. Univariate and multivariate analyses using logistic regression and decision curve analyses were performed. All three markers were predictors of a tumor volume≥0.5 mL. Only PHI predicted Gleason score≥7. T2 score and PHI were both independent predictors of extracapsular extension(≥pT3), while multifocality was only predicted by PCA3 score. Moreover, when compared to a base model (age, digital rectal examination, serum PSA, and Gleason sum at biopsy), the addition of both PCA3 score and PHI to the base model induced a significant increase (+12%) when predicting tumor volume>0.5 mL. PHI and urinary PCA3 and T2 scores can be considered as complementary predictors of cancer aggressiveness at prostatectomy.

Comparative Evaluation of Urinary PCA3 and TMPRSS2: ERG Scores and Serum PHI in Predicting Prostate Cancer Aggressiveness

Directory of Open Access Journals (Sweden)

Lucile Tallon

2014-07-01

Full Text Available It has been suggested that urinary PCA3 and TMPRSS2:ERG fusion tests and serum PHI correlate to cancer aggressiveness-related pathological criteria at prostatectomy. To evaluate and compare their ability in predicting prostate cancer aggressiveness, PHI and urinary PCA3 and TMPRSS2:ERG (T2 scores were assessed in 154 patients who underwent radical prostatectomy for biopsy-proven prostate cancer. Univariate and multivariate analyses using logistic regression and decision curve analyses were performed. All three markers were predictors of a tumor volume ≥0.5 mL. Only PHI predicted Gleason score ≥7. T2 score and PHI were both independent predictors of extracapsular extension (≥pT3, while multifocality was only predicted by PCA3 score. Moreover, when compared to a base model (age, digital rectal examination, serum PSA, and Gleason sum at biopsy, the addition of both PCA3 score and PHI to the base model induced a significant increase (+12% when predicting tumor volume >0.5 mL. PHI and urinary PCA3 and T2 scores can be considered as complementary predictors of cancer aggressiveness at prostatectomy.

hERG blocking potential of acids and zwitterions characterized by three thresholds for acidity, size and reactivity

DEFF Research Database (Denmark)

Nikolov, Nikolai Georgiev; Dybdahl, Marianne; Jonsdottir, Svava Osk

2014-01-01

with a concordance of 91% by a decision tree based on the rule. Two external validations were performed with sets of 35 and 48 observations, respectively, both showing concordances of 91%. In addition, a global QSAR model of hERG blocking was constructed based on a large diverse training set of 1374 chemicals...... covering all ionization classes, externally validated showing high predictivity and compared to the decision tree. The decision tree was found to be superior for the acids and zwitterionic ampholytes classes....

X-linked retinoschisis: RS1 mutation severity and age affect the ERG phenotype in a cohort of 68 affected male subjects.

Science.gov (United States)

Bowles, Kristen; Cukras, Catherine; Turriff, Amy; Sergeev, Yuri; Vitale, Susan; Bush, Ronald A; Sieving, Paul A

2011-11-29

To assess the effect of age and RS1 mutation on the phenotype of X-linked retinoschisis (XLRS) subjects using the clinical electroretinogram (ERG) in a cross-sectional analysis. Sixty-eight XLRS males 4.5 to 55 years of age underwent genotyping, and the retinoschisis (RS1) mutations were classified as less severe (27 subjects) or more severe (41 subjects) based on the putative impact on the protein. ERG parameters of retinal function were analyzed by putative mutation severity with age as a continuous variable. The a-wave amplitude remained greater than the lower limit of normal (mean, -2 SD) for 72% of XLRS males and correlated with neither age nor mutation class. However, b-wave and b/a-ratio amplitudes were significantly lower in the more severe than in the less severe mutation groups and in older than in younger subjects. Subjects up to 10 years of age with more severe RS1 mutations had significantly greater b-wave amplitudes and faster a-wave trough implicit times than older subjects in this group. RS1 mutation putative severity and age both had significant effects on retinal function in XLRS only in the severe mutation group, as judged by ERG analysis of the b-wave amplitude and the b/a-ratio, whereas the a-wave amplitude remained normal in most. A new observation was that increasing age (limited to those aged 55 and younger) caused a significant delay in XLRS b-wave onset (i.e., a-wave implicit time), even for those who retained considerable b-wave amplitudes. The delayed b-wave onset suggested that dysfunction of the photoreceptor synapse or of bipolar cells increases with age of XLRS subjects.

Research priorities by professional background - A detailed analysis of the James Lind Alliance Priority Setting Partnership.

Science.gov (United States)

Arulkumaran, Nishkantha; Reay, Hannah; Brett, Stephen J

2016-05-01

The Intensive Care Foundation, in partnership with the James Lind Alliance, has supported a national project to identify and prioritise unanswered questions about adult intensive care that are important to people who have been critically ill, their families, and the health professionals who care for them. We conducted a secondary analysis to explore differences in priorities determined by different respondent groups in order to identify different groups' perceptions of gaps in knowledge. There were two surveys conducted as part of the original project. Survey 1 comprised a single open question to identify important research topics; survey 2 aimed to prioritise these topics using a 10-point Likert scale. In survey 1, despite clear differences in suggestions amongst the respondent groups, themes of comfort/communication and post-ICU rehabilitation were the within the top 2 suggestions across all groups. Patients and relatives suggested research topics to which they could easily relate, whereas there was a greater breadth of suggestions from clinicians. In survey 2, the number of research priorities that received a mode score of 10 varied from 1 to 36. Patients scored 36 out of the 37 topics with a mode score of 10. All other groups scored topics with more discrimination, with the number of topics with a mode score of 10 ranging from 1 to 20. Differences in the proportions of the representative groups are therefore unlikely to have translated to an impartial conclusion. Clinicians, patients, and family members have jointly identified the research priorities for UK ICM practice.

Vene kirjanduse õpik lõhestab kirjanikud headeks ja pahadeks / Vaapo Vaher

Index Scriptorium Estoniae

Vaher, Vaapo, 1945-

2003-01-01

Arvustus: XX sajandi vene kirjandus. I, Luule / [koostanud Katrin Kalamees ja Maritsa Lens. Tallinn] : Avita, 2002; XX sajandi vene kirjandus. II, Proosa / [koostanud Katrin Kalamees ja Maritsa Lens. Tallinn] : Avita, 2002. Vastukajad: Tuch, Boris. Dva toma oshibok // Estonija (2003) 28. apr., lk. 9 ; Kalamees, Katrin ; Lens, Maritsa. Vastuseid Vaapo Vaheri küsimistele // Eesti Päevaleht (2003) 2. mai, lk. 17

Functional Characterization of the Protein Product of the Prostate Carcinoma Gene Fusion TMPRSS2:ERG Using the Proteomic and Microarray Analyses

Science.gov (United States)

2009-07-01

AD_________________ ( Leave blank) Award Number: W81XWH-08-1-0048 TITLE: Functional... Guava ™ FACS analyzer with the ViaCount™ kit (Millipore). As shown in Fig. 7, VCaP cells infected with ERG or ERGa once again failed to proliferate...and the cell numbers in each series were determined using the Guava ViaCount™ kit. Average values of the triplicate samples are shown. Milestone

Interactions between charged residues in the transmembrane segments of the voltage-sensing domain in the hERG channel.

Science.gov (United States)

Zhang, M; Liu, J; Jiang, M; Wu, D-M; Sonawane, K; Guy, H R; Tseng, G-N

2005-10-01

Studies on voltage-gated K channels such as Shaker have shown that positive charges in the voltage-sensor (S4) can form salt bridges with negative charges in the surrounding transmembrane segments in a state-dependent manner, and different charge pairings can stabilize the channels in closed or open states. The goal of this study is to identify such charge interactions in the hERG channel. This knowledge can provide constraints on the spatial relationship among transmembrane segments in the channel's voltage-sensing domain, which are necessary for modeling its structure. We first study the effects of reversing S4's positive charges on channel activation. Reversing positive charges at the outer (K525D) and inner (K538D) ends of S4 markedly accelerates hERG activation, whereas reversing the 4 positive charges in between either has no effect or slows activation. We then use the 'mutant cycle analysis' to test whether D456 (outer end of S2) and D411 (inner end of S1) can pair with K525 and K538, respectively. Other positive charges predicted to be able, or unable, to interact with D456 or D411 are also included in the analysis. The results are consistent with predictions based on the distribution of these charged residues, and confirm that there is functional coupling between D456 and K525 and between D411 and K538.

Measurements of differential cross sections for the reactions 6,7Li(n,d)5,6He and 6,7Li(n,t)4,5He at 14.1 MeV

International Nuclear Information System (INIS)

Shirato, Shoji; Hata, Kazuhiro; Ando, Yoshiaki; Shibuya, Shinji; Shibata, Keiichi.

1989-08-01

A summary of our measured cross sections for the 14.1 MeV neutron-induced reactions on lithium isotopes has been presented. Our data were measured with two counter telescopes, each of which consisted of two gas proportional counters and silicon ΔE and E detectors. Measured energy spectra of deuterons and tritons from 6 Li(n,d)n 4 He and 7 Li(n,t)n 4 He, respectively, were analyzed by a simple final-state interaction theory. Measured angular distributions for these reactions as well as 6 Li(n,t) 4 He and 7 Li(n,d) 6 He were analyzed by exact finite-range distorted wave Born approximation (EFR-DWBA) calculations. Spectroscopic factors extracted from the EFR-DWBA analyses have been compared with theoretical predictions. (author)

Removal of ammonium ions by laboratory-synthesized zeolite linde type A adsorption from water samples affected by mining activities in Ghana.

Science.gov (United States)

Kwakye-Awuah, Bright; Labik, Linus Kweku; Nkrumah, Isaac; Williams, Craig

2014-03-01

Ammonium ion adsorption by laboratory-synthesized zeolite (linde type A; LTA) was investigated in batch kinetics experiments. Synthesized zeolite LTA was characterized by X-ray diffraction, scanning electron microscopy, energy-dispersive X-ray spectroscopy, thermogravimetric analysis, Fourier transform infrared spectroscopy and particle size analysis. Water samples were taken from the Nyam and Tano rivers in Ghana, and 0.8 g of zeolite was added to 100 ml portions of each sample. Portions of the samples were withdrawn every 30 min for 150 min and the concentration of ammonia in each sample was determined. The removal efficiency of zeolite LTA was evaluated by retrieving the zeolite from the water samples and adding to a fresh sample to repeat the process. Equilibrium data were fitted by Langmuir and Freundlich isotherms. Maximum adsorption capacities were 72.99 mg g(-1) for samples from the River Nyam and 72.87 mg g(-1) for samples from the River Tano. The equilibrium kinetic data were analysed using adsorption kinetic models: pseudo-first order and pseudo-second order kinetic models. Linear regression was used to estimate the adsorption and kinetic parameters. The results showed that the adsorption followed pseudo-second order kinetics and suggest that zeolite LTA is a good adsorbent for the removal of nitrogen ammonia from water.

Vormiriietus teeb koolilapse shikiks ja paneb väärikalt käituma / Sandra Maasalu

Index Scriptorium Estoniae

Maasalu, Sandra

2008-01-01

Eesti koolides kantavatest koolivormidest. Pikemalt Katrin Kivi disainitud Tallinna Saksa gümnaasiumi koolivormist ja Tallinna Arte gümnaasiumi koolivormist. Katrin Kivi ja Peeter Kreitzbergi kommentaarid. 8 ill.

Blogs und Journalismus – Konkurrenz oder Ergänzung? – Das Verhältnis von Blogs und Journalismus in Deutschland

Directory of Open Access Journals (Sweden)

Saskia Leidinger

2015-12-01

Full Text Available Mit der Frage, ob „Blogs und Journalismus - Konkurrenz oder Ergänzung“ sind, beschäftigt sich Saskia Leidinger in dem gleichnamigen Essay über „das Verhältnis von Blogs und Journalismus in Deutschland“. In vergleichender Perspektive richtet die Autorin ihr Hauptaugenmerk auf die Arbeitsweise sowie die Eigen- und Fremdwahrnehmung von Bloggern und Journalisten, um Gemeinsamkeiten und Unterschiede herauszustellen und ihre je spezifische Funktion innerhalb der der heutigen Informationsgesellschaft einzugrenzen.

Multifocal ERG reveals long distance effects of a local bleach in the retina.

Science.gov (United States)

Kretschmann, U; Tornow, R P; Zrenner, E

1998-06-01

To examine the distribution of ERG-activity in the central visual field after local bleaching of the fovea, multifocal electroretinograms were recorded in eight normal volunteers before, during and after recurrent light exposure. During bleaching (90% bleached pigment), the response density (scalar product) of the foveal area (0-2 degrees eccentricity) decreased from 10.7 +/- 3.5 to 4.1 +/- 1.9 nV/degree2 (P < 0.001). The average activity in the extrafoveal macular area was unchanged, while the amplitudes were frequently (in 53 of 54 areas) enhanced at 5-30.5 degrees eccentricity. Here the average response density changed from 3.1 +/- 0.9 to 3.5 +/- 1.0 nV/degree2 (P < 0.001). A fast recovery of foveal responses after cessation of bleaching occurred. Besides a strong decrease of response in the directly bleached area, local bleaching led to enhanced activity mainly 3-27 degrees distant from the bleached area.

Evaluation procedure for Service Level C and D upper shelf toughness criteria for Linde 80 weld material

International Nuclear Information System (INIS)

Gamble, R.M.

1993-09-01

Procedures have been defined to evaluate the upper shelf toughness criteria recently defined by ASME Section XI Subgroup on Evaluation Standards for ASME Service Level C and D conditions. These procedures and the ASME criteria were applied to assess the upper toughness requirements for axial Linde 80 welds in a typical PWR reactor pressure vessel beltline geometry. Because there is a wide spectrum of possible Level C and D events, the evaluation was performed for a bounding thermal transient and results were obtained to determine allowable pressure versus upper shelf energy. The allowable pressure for the bounding thermal transient was found to be above normal operating pressure for upper shelf energies equal to and greater than 40 ft-lb. Because a bounding thermal transient was used, the allowable pressures determined in this work should be minimum values. The results from this work provide a screening criterion to quickly identify limiting transients that may require more detailed analysis and an analysis procedure to assess compliance with ASME upper shelf energy criteria for Service Level C and D events. For events with significant thermal transients, such as those evaluated in this work, the transient pressure typically decreases rapidly from normal operating pressure to 1,500 psi or less before the maximum thermal K I , is reached. Comparing this pressure range with the allowable pressure versus upper shelf energy curves determined in this work indicates that the transient pressures are significantly less than the allowables computed for Level C and D events; consequently, Level A/B conditions will likely dictate the upper shelf requirements for most applications

L'Inde de 1919 à 1941 : nationalismes, « communalisme », prosélytisme et fondamentalisme

Directory of Open Access Journals (Sweden)

Marc Gaborieau

2009-05-01

Full Text Available Durant l'entre-deux-guerres, se produisit la rupture définitive, sur le plan politique, entre hindous et musulmans, avec la revendication dès 1930 par le poète philosophe Iqbâl (1876-1938 d'un État séparé pour les musulmans, dont le nom (Pakistan fut forgé dès 1935. Une rupture idéologique avait précédé ce divorce politique. La droite hindoue avait forgé dès 1923 la notion d' « hindouité » (hin-dutva fondée sur un rejet de l'héritage de l'Inde médiévale musulmane, notamment moghole. Les musulmans ripostèrent avec Mawdûdî (1903-1979 qui, dans son premier livre de 1927, fit l'apologie du jihâd guerrier, cherchant à réhabiliter l'islam médiéval dans sa pureté et son agressivité. Ces écrits portaient en germe la jamâ'at-i Islâmî, organisation militante qui vit formellement le jour en 1941. La détérioration des relations entre les communautés religieuses alla de pair avec cette double rupture : cette confrontation est appelé « communalisme » en anglo-indien. Des organisations missionnaires prosélytes furent créées de part et d'autre, dont la Tablîghî Jamâ'at pour les musulmans en 1927.

Hüvad ärritunud pedagoogilised daamid / Vaapo Vaher

Index Scriptorium Estoniae

Vaher, Vaapo, 1945-

2003-01-01

Arvustus: XX sajandi vene kirjandus. I, Luule / [koostanud Katrin Kalamees ja Maritsa Lens. Tallinn] : Avita, 2002; XX sajandi vene kirjandus. II, Proosa / [koostanud Katrin Kalamees ja Maritsa Lens. Tallinn] : Avita, 2002. Vastuseks Vaapo Vaheri arvustusele "Vene kirjanduse õpik lõhestab kirjanikud headeks ja pahadeks", Eesti Päevaleht : Arkaadia, 25. apr. 2003: Kalamees, Katrin; Lens, Maritsa. Vastuseid Vaapo Vaheri küsimistele, Eesti Päevaleht, 2. mai, lk. 17; Vt. ka vastukajad: Tuch, Boris. Dva toma oshibok // Estonija (2002) 28. apr., lk. 9

Mutation in Torenia fournieri Lind. UFO homolog confers loss of TfLFY interaction and results in a petal to sepal transformation.

Science.gov (United States)

Sasaki, Katsutomo; Yamaguchi, Hiroyasu; Aida, Ryutaro; Shikata, Masahito; Abe, Tomoko; Ohtsubo, Norihiro

2012-09-01

We identified a Torenia fournieri Lind. mutant (no. 252) that exhibited a sepaloid phenotype in which the second whorls were changed to sepal-like organs. This mutant had no stamens, and the floral organs consisted of sepals and carpels. Although the expression of a torenia class B MADS-box gene, GLOBOSA (TfGLO), was abolished in the 252 mutant, no mutation of TfGLO was found. Among torenia homologs such as APETALA1 (AP1), LEAFY (LFY), and UNUSUAL FLORAL ORGANS (UFO), which regulate expression of class B genes in Arabidopsis, only accumulation of the TfUFO transcript was diminished in the 252 mutant. Furthermore, a missense mutation was found in the coding region of the mutant TfUFO. Intact TfUFO complemented the mutant phenotype whereas mutated TfUFO did not; in addition, the transgenic phenotype of TfUFO-knockdown torenias coincided with the mutant phenotype. Yeast two-hybrid analysis revealed that the mutated TfUFO lost its ability to interact with TfLFY protein. In situ hybridization analysis indicated that the transcripts of TfUFO and TfLFY were partially accumulated in the same region. These results clearly demonstrate that the defect in TfUFO caused the sepaloid phenotype in the 252 mutant due to the loss of interaction with TfLFY. © 2012 The Authors. The Plant Journal © 2012 Blackwell Publishing Ltd.

"Rudi" polutshil glavnõi priz

Index Scriptorium Estoniae

2006-01-01

Lastefilm "Ruudi" (stsenaristid Katrin Laur, Aare Toikka, Aarne Mägi : režissöör Katrin Laur : nimiosas lapsnäitleja Paul Oskar Soe) sai Tokyo 14. lastefilmide festivalil Kodomotachino parima mängufilmi auhinna

Grand prix / J. U.

Index Scriptorium Estoniae

J. U.

2006-01-01

Lastefilm "Ruudi" (stsenaristid Katrin Laur, Aare Toikka, Aarne Mägi : režissöör Katrin Laur : nimiosas lapsnäitleja Paul Oskar Soe) sai Tokyo 14. lastefilmide festivalil Kodomotachino parima mängufilmi auhinna

"Ruudi" võitis Tokyos

Index Scriptorium Estoniae

2006-01-01

Lastefilm "Ruudi" (stsenaristid Katrin Laur, Aare Toikka, Aarne Mägi : režissöör Katrin Laur : nimiosas lapsnäitleja Paul Oskar Soe) sai Tokyo 14. lastefilmide festivalil Kodomotachino parima mängufilmi auhinna

Два тома ошибок / Борис Тух

Index Scriptorium Estoniae

Тух, Борис, 1946-

2003-01-01

Arvustus: XX sajandi vene kirjandus. I, Luule / [koostanud Katrin Kalamees ja Maritsa Lens. Tallinn] : Avita, 2002; XX sajandi vene kirjandus. II, Proosa / [koostanud Katrin Kalamees ja Maritsa Lens. Tallinn] : Avita, 2002. Vastuseks Vaapo Vaheri arvustusele "Vene kirjanduse õpik lõhestab kirjanikud headeks ja pahadeks", Eesti Päevaleht : Arkaadia, 25. apr. 2003. Vt. ka vastukajad: Kalamees, Katrin; Lens, Maritsa. Vastuseid Vaapo Vaheri küsimistele, Eesti Päevaleht, 2. mai, lk. 17; Vaher, Vaapo. Hüvad ärritunud pedagoogilised daamid, Eesti Päevaleht : Arkaadia, 2. mai, lk. 17

Reval Hotel Lietuva Vilniuses : Konstitucijos pr. 20 / Piret Lindpere

Index Scriptorium Estoniae

Lindpere, Piret, 1963-

2004-01-01

Vilniuse hotelli "Lietuva" renoveerimine. Arhitektuurse projekti koostaja Rootsi arhitektuuribüroo AB SWECO (arhitektid Aare Saks, Nils Palm. Sisekujundus: Vaikla Disain AS (Katrin ja Argo Vaikla, Liis Lindvere, Peeter Loo). Kommenteerivad Argo ja Katrin Vaikla. 3 ill

Self-assembly in poly(dimethylsiloxane)-poly(ethylene oxide) block copolymer template directed synthesis of Linde type A zeolite.

Science.gov (United States)

Bonaccorsi, Lucio; Calandra, Pietro; Kiselev, Mikhail A; Amenitsch, Heinz; Proverbio, Edoardo; Lombardo, Domenico

2013-06-11

We describe the hydrothermal synthesis of zeolite Linde type A (LTA) submicrometer particles using a water-soluble amphiphilic block copolymer of poly(dimethylsiloxane)-b-poly(ethylene oxide) as a template. The formation and growth of the intermediate aggregates in the presence of the diblock copolymer have been monitored by small-angle X-ray scattering (SAXS) above the critical micellar concentration at a constant temperature of 45 °C. The early stage of the growth process was characterized by the incorporation of the zeolite LTA components into the surface of the block copolymer micellar aggregates with the formation of primary units of 4.8 nm with a core-shell morphology. During this period, restricted to an initial time of 1-3 h, the core-shell structure of the particles does not show significant changes, while a subsequent aggregation process among these primary units takes place. A shape transition of the SAXS profile at the late stage of the synthesis has been connected with an aggregation process among primary units that leads to the formation of large clusters with fractal characteristics. The formation of large supramolecular assemblies was finally verified by scanning electron microscopy, which evidenced the presence of submicrometer aggregates with size ranging between 100 and 300 nm, while X-ray diffraction confirmed the presence of crystalline zeolite LTA. The main finding of our results gives novel insight into the mechanism of formation of organic-inorganic mesoporous materials based on the use of a soft interacting nanotemplate as well as stimulates the investigation of alternative protocols for the synthesis of novel hybrid materials with new characteristics and properties.

Shared research priorities for pessary use in women with prolapse: results from a James Lind Alliance Priority Setting Partnership.

Science.gov (United States)

Lough, Kate; Hagen, Suzanne; McClurg, Doreen; Pollock, Alex

2018-04-28

To identify the shared priorities for future research of women affected by and clinicians involved with pessary use for the management of prolapse. A priority setting project using a consensus method. A James Lind Alliance Pessary use for prolapse Priority Setting Partnership (JLA Pessary PSP) conducted from May 2016 to September 2017 in the UK. The PSP was run by a Steering Group of three women with experience of pessary use, three experienced clinicians involved with management of prolapse, two researchers with relevant experience, a JLA adviser and a PSP leader. Two surveys were conducted in 2016 and 2017. The first gathered questions about pessaries, and the second asked respondents to prioritise a list of questions. A final workshop was held on 8 September 2017 involving 10 women and 13 clinician representatives with prolapse and pessary experience. A top 10 list of priorities for future research in pessary use for prolapse was agreed by consensus. Women with experience of pessary use and clinicians involved with prolapse management have worked together to determine shared priorities for future research. Aligning the top 10 results with existing research findings will highlight the gaps in current evidence and signpost future research to areas of priority. Effective dissemination of the results will enable research funding bodies to focus on gathering the evidence to answer the questions that matter most to those who will be affected. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

High-energy electron experiments (HEP) aboard the ERG (Arase) satellite

Science.gov (United States)

Mitani, Takefumi; Takashima, Takeshi; Kasahara, Satoshi; Miyake, Wataru; Hirahara, Masafumi

2018-05-01

This paper reports the design, calibration, and operation of high-energy electron experiments (HEP) aboard the exploration of energization and radiation in geospace (ERG) satellite. HEP detects 70 keV-2 MeV electrons and generates a three-dimensional velocity distribution for these electrons in every period of the satellite's rotation. Electrons are detected by two instruments, namely HEP-L and HEP-H, which differ in their geometric factor (G-factor) and range of energies they detect. HEP-L detects 70 keV-1 MeV electrons and its G-factor is 9.3 × 10-4 cm2 sr at maximum, while HEP-H observes 0.7-2 MeV electrons and its G-factor is 9.3 × 10-3 cm2 sr at maximum. The instruments utilize silicon strip detectors and application-specific integrated circuits to readout the incident charge signal from each strip. Before the launch, we calibrated the detectors by measuring the energy spectra of all strips using γ-ray sources. To evaluate the overall performance of the HEP instruments, we measured the energy spectra and angular responses with electron beams. After HEP was first put into operation, on February 2, 2017, it was demonstrated that the instruments performed normally. HEP began its exploratory observations with regard to energization and radiation in geospace in late March 2017. The initial results of the in-orbit observations are introduced briefly in this paper.[Figure not available: see fulltext.

Revisión sistemática cualitativa del uso de cuestionarios para el diagnóstico de ERGE en pediatría

Directory of Open Access Journals (Sweden)

RR Hernández-Pliego

2016-04-01

Full Text Available INTRODUCCIÓN: el uso de cuestionarios para identificar síntomas de enfermedad por reflujo gastroesofágico (ERGE y su aplicación en población pediátrica es limitado, sobre todo en niños menores y lactantes, en los que resulta imposible conocer los síntomas debido a la incapacidad de manifestarlos de manera objetiva.   OBJETIVO: realizar una revisión sistemática de la literatura en población pediátrica con sospecha de ERGE, para evaluar el uso de cuestionarios como herramienta diagnóstica para esta enfermedad.   MATERIAL Y MÉTODOS: se realizó una búsqueda exhaustiva de la literatura en diversas bases de datos. La selección de los estudios fue realizada por dos investigadores expertos en el tema. La estrategia de búsqueda estuvo compuesta de las palabras clave: Gastroesophageal Reflux disease, Infant Gastroesophageal Reflux Questionnaire (IGERQ, infant, child, children, questionnaire. La calidad de los estudios fue evaluada con la escala Newcastle-Ottawa.   RESULTADOS: con la estrategia de búsqueda realizada fueron seleccionados tres estudios, los cuales utilizaron diferentes cuestionarios en poblaciones distintas: en 2006, Kleinman evaluó la confiabilidad del cuestionario IGER-Q en 185 pacientes menores de 18 meses obteniéndose 0.86 0.87; en 2005, Deal evaluó 64 pacientes de 1-11 meses y 63 pacientes de 1-4 años reportando una sensibilidad de 90 y 85% para cada grupo de edad, respectivamente y especificidad de 83 y 81.5%, respectivamente; y Stordal, en 2005, evaluó 99 pacientes de 7-16 años con una sensibilidad de 75% y especificidad de 96%.    CONCLUSIÓN: el uso de los cuestionarios como herramienta diagnóstica de ERGE en pacientes pediátricos es escaso y la evidencia clínica disponible no es suficiente para realizar una recomendación apropiada.

Pildiseiklusi maal ja merel / Neeme Korv

Index Scriptorium Estoniae

Korv, Neeme, 1974-

2010-01-01

Arvustus: Hergé, pseud. Kuldsõrgadega krabi / [prantsuse keelest tõlkinud Katrin Kaarep. Tallinn] : Tänapäev, 2010. (Tintini seiklused) ; Hergé, pseud. Must last / [prantsuse keelest tõlkinud Katrin Kaarep. Tallinn] : Tänapäev, 2010. (Tintini seiklused)

Patients with Long QT Syndrome Due to Impaired hERG-encoded Kv11.1 Potassium Channel Have Exaggerated Endocrine Pancreatic and Incretin Function Associated with Reactive Hypoglycemia

DEFF Research Database (Denmark)

Hyltén-Cavallius, Louise; Iepsen, Eva W; Wewer Albrechtsen, Nicolai J

2017-01-01

Background -Loss-of-function mutations in hERG (encoding the Kv11.1 voltage-gated potassium channel) cause long QT syndrome (LQT2) due to prolonged cardiac repolarization. However, Kv11.1 is also present in pancreatic α and β cells and intestinal L and K cells, secreting glucagon, insulin, and th...

Complete genome sequence of Arthrobacter alpinus ERGS4:06, a yellow pigmented bacterium tolerant to cold and radiations isolated from Sikkim Himalaya.

Science.gov (United States)

Kumar, Rakshak; Singh, Dharam; Swarnkar, Mohit Kumar; Singh, Anil Kumar; Kumar, Sanjay

2016-02-20

Arthrobacter alpinus ERGS4:06, a yellow pigmented bacterium which exhibited tolerance to cold and UV radiations was isolated from the glacial stream of East Rathong glacier in Sikkim Himalaya. Here we report the 4.3Mb complete genome assembly that has provided the basis for potential role of pigments as a survival strategy to combat stressed environment of cold and high UV-radiation and additionally the ability to produce cold active industrial enzymes. Copyright © 2016 Elsevier B.V. All rights reserved.

Eesti lastefilm räägib üksikutest lastest ja üksikutest vanematest / Jürgen Rooste, Marko Martinson

Index Scriptorium Estoniae

Rooste, Jürgen, 1979-

2006-01-01

Lastefilm "Ruudi" : stsenaristid Katrin Laur, Aare Toikka, Aarne Mägi : režissöör Katrin Laur : nimiosas lapsnäitleja Paul Oskar Soe : produtsent Piret Tibbo-Hudgins : operaator Rein Kotov : kunstnik Toomas Hõrak : Allfilm - MRP Matila Röhr Productions - Schmidtz Katze Filmkollektiv 2006

Irresponsiveness of two retinoblastoma cases to conservative therapy correlates with up- regulation of hERG1 channels and of the VEGF-A pathway

Directory of Open Access Journals (Sweden)

La Torre Agostino

2010-09-01

Full Text Available Abstract Background Treatment strategies for Retinoblastoma (RB, the most common primary intraocular tumor in children, have evolved over the past few decades and chemoreduction is currently the most popular treatment strategy. Despite success, systemic chemotherapeutic treatment has relevant toxicity, especially in the pediatric population. Antiangiogenic therapy has thus been proposed as a valuable alternative for pediatric malignancies, in particolar RB. Indeed, it has been shown that vessel density correlates with both local invasive growth and presence of metastases in RB, suggesting that angiogenesis could play a pivotal role for both local and systemic invasive growth in RB. We present here two cases of sporadic, bilateral RB that did not benefit from the conservative treatment and we provide evidence that the VEGF-A pathway is significantly up-regulated in both RB cases along with an over expression of hERG1 K+ channels. Case presentation Two patients showed a sporadic, bilateral RB, classified at Stage II of the Reese-Elsworth Classification. Neither of them got benefits from conservative treatment, and the two eyes were enucleated. In samples from both RB cases we studied the VEGF-A pathway: VEGF-A showed high levels in the vitreous, the vegf-a, flt-1, kdr, and hif1-α transcripts were over-expressed. Moreover, both the transcripts and proteins of the hERG1 K+ channels turned out to be up-regulated in the two RB cases compared to the non cancerous retinal tissue. Conclusions We provide evidence that the VEGF-A pathway is up-regulated in two particular aggressive cases of bilateral RB, which did not experience any benefit from conservative treatment, showing the overexpression of the vegf-a, flt-1, kdr and hif1-α transcripts and the high secretion of VEGF-A. Moreover we also show for the first time that the herg1 gene transcripts and protein are over expressed in RB, as occurs in several aggressive tumors. These results further stress

"Ansip tshmo" kak objekt iskusstva / Nikolai Karajev

Index Scriptorium Estoniae

Karajev, Nikolai, 1978-

2007-01-01

Briti kunstniku Clare Charnley multimeediainstallatsioon أGift of tongues / keelte andؤ Hobusepea galeriis Tallinnas. Eestipoolseks kaaskunstnikuks projektis on Katrin Kivimaa. Performance'ist أKõneؤ ja alumises galeriis näidatavast videoinstallatsioonist. Clare Charnley ja Katrin Kivimaa koostatud raamatust "So Communication : Translating Each Other's Words"

EmERGE project: Evaluating mHealth technology in HIV to improve Empowerment and healthcare utilisation

Energy Technology Data Exchange (ETDEWEB)

Chausa, P.; Gomez, A.J.; Apers, L.; Henwood, F.; Mandalia, S.; Wallitt, E.; Leon, A.; Begovac, J.; Borges, M.; Brown, A.; Block, K.; Glaysher, B.; Whetham, J.

2016-07-01

The EmERGE project (http://www.emergeproject.eu/) will develop a mHealth platform to enable self-management of HIV in patients with stable disease. The platform will build upon and integrate the existing mHealth solutions operated by pioneering healthcare providers in the UK and Spain and apply a rigorous co-design approach to ensure patient and clinician input to the solution. The platform will provide users with web based (clinicians) and mobile device applications (patients) which interface securely with relevant medical data and facilitate remote access to key healthcare providers. EATG, the leading European HIV patient organisation, will provide a direct and deep interaction with representative patients and clinicians from 5 EU countries. The platform and interfaces will be validated in a large study of 3900 patients using a tailored Health Technology Assessment process: the Model for Assessment of Telemedicine applications, specifically developed for the assessment of mHealth solutions including translatability as a key factor. (Author)

Nontoxic concentration of ceftazidime and flomoxef sodium for intravitreal use--evaluated by in-vitro ERG.

Science.gov (United States)

Tanabe, J; Kitano, K; Suzuki, T; Okayama, Y; Mochizuki, K; Kawasaki, K

1990-01-01

The effects of ceftazidime (CAZ) and flomoxef sodium (FMOX) on the in-vitro electroretinogram (ERG) of albino rabbits were studied. The a-wave, the b-wave and the oscillatory potential (OP) were unchanged by 0.3mM (0.19mg/ml) CAZ-containing solution. The OP was suppressed by 0.5mM (0.32mg/ml) CAZ. The a-wave, the b-wave and the OP were unchanged by 0.5mM (0.26mg/ml) FMOX. The OP was suppressed and its peak latency was delayed by 2mM (0.52mg/ml) FMOX. The concentration of 0.3mM (0.19mg/ml) CAZ was higher than its minimum inhibitory concentration (MIC) against Staphylococcus aureus, Staphylococcus epidermidis, Pseudomonas aeruginosa, Serratia marcescens and Propionibacterium acnes. The concentration of 0.5mM (0.26mg/ml) FMOX was higher than its MIC against Staphylococcus aureus, Staphylococcus epidermidis, Serratia marcescens and Propionibacterium acnes.

Tekstiilikonverents Hispaanias / Lea Pruuli

Index Scriptorium Estoniae

Pruuli, Lea

1998-01-01

8. - 16. märtsini Barcelonas ja Madridis European Textile Networki konverentsist. Eesti tekstiilikunstnike delegatsiooni kuulusid Katrin Pere, Signe Kivi, Lylian Meister, Merike Männi, Aune Taamal, Aet Ollisaar, Anne Tootma ja Lea Pruuli. Eesti tekstiilikunstist kõnelesid Signe Kivi, Katrin Pere. K. Pere valiti ETN juhatuse vaatlejaliikmeks.

Eramu Leppneemes = Private residence in Leppneeme

Index Scriptorium Estoniae

2011-01-01

Arhitekt Lembit Torgi poolt projekteeritud eramu sisekujundusest. Sisearhitektid Argo Vaikla, Katrin Vaikla, Mari-Liis Süld (Vaikla Disain). Kabineti puitmööbli ja garderoobi sisustuse projekteeris Vaikla Disain. Loetletud Mari-Liis Sülla tehtud töid ning Argo ja Katrin Vaikla ühiselt tehtud töid

Functional characterization of a novel hERG variant in a family with recurrent sudden infant death syndrome: Retracting a genetic diagnosis.

Science.gov (United States)

Sergeev, Valentine; Perry, Frances; Roston, Thomas M; Sanatani, Shubhayan; Tibbits, Glen F; Claydon, Thomas W

2018-03-01

Long QT syndrome (LQTS) is the most common cardiac ion channelopathy and has been found to be responsible for approximately 10% of sudden infant death syndrome (SIDS) cases. Despite increasing use of broad panels and now whole exome sequencing (WES) in the investigation of SIDS, the probability of identifying a pathogenic mutation in a SIDS victim is low. We report a family-based study who are afflicted by recurrent SIDS in which several members harbor a variant, p.Pro963Thr, in the C-terminal region of the human-ether-a-go-go (hERG) gene, published to be responsible for cases of LQTS type 2. Functional characterization was undertaken due to the variable phenotype in carriers, the discrepancy with published cases, and the importance of identifying a cause for recurrent deaths in a single family. Studies of the mutated ion channel in in vitro heterologous expression systems revealed that the mutation has no detectable impact on membrane surface expression, biophysical gating properties such as activation, deactivation and inactivation, or the amplitude of the protective current conducted by hERG channels during early repolarization. These observations suggest that the p.Pro963Thr mutation is not a monogenic disease-causing LQTS mutation despite evidence of co-segregation in two siblings affected by SIDS. Our findings demonstrate some of the potential pitfalls in post-mortem molecular testing and the importance of functional testing of gene variants in determining disease-causation, especially where the impacts of cascade screening can affect multiple generations. Copyright © 2017 Elsevier B.V. All rights reserved.

Haabersti vaba aja keskus = Haabersti recreational centre

Index Scriptorium Estoniae

2008-01-01

Haabersti vaba aja keskuse (Ehitajate tee 109A/2, Tallinn) sisekujundusest. Arhitektid: Peeter Pere ja Urmas Muru (AB Muru & Pere). Sisearhitekt: Katrin Kaevats (Salto AB). Katrin Kaevatsist, tema tähtsamad tööd. I-IV korruse plaan, värv. välisvaade, 11 sisevaadet, foto K. Kaevatsist

FIBIT - Fashion is back in Tallinn / Marina Poltavtseva

Index Scriptorium Estoniae

Poltavtseva, Marina

2004-01-01

Moepäevad FIBIT Viru keskuses. Üks idee algatajaid on moekunstnik Katrin Kuldma. 1. oktoobril näidatakse soome moekunstniku Ritva-Liisa Pohjalaineni kollektsiooni Allergia - From Dreams to the Unique. Teisi moedemonstratsioone, millede stilistideks on Riina Põldroos, Aldo Järvsoo, Tanel Veenre ja Katrin Kuldma. Rõivad on valitud Viru keskuse kauplustest

Kas läheb ka Ruudi tapmiseks? / Kati Murutar

Index Scriptorium Estoniae

Murutar, Kati, 1967-

2006-01-01

Lastefilm "Ruudi" : stsenaristid Katrin Laur, Aare Toikka, Aarne Mägi : režissöör Katrin Laur : nimiosas lapsnäitleja Paul Oskar Soe : Allfilm - MRP Matila Röhr Productions - Schmidtz Katze Filmkollektiv 2006. Võetud kõne alla ka Peeter Simmi "Kõrini!" ja Peeter Urbla "Stiilipeo" arvustaja meelest teenimatult mahategevad retsensioonid

Increased vulnerability of human ventricle to re-entrant excitation in hERG-linked variant 1 short QT syndrome.

Directory of Open Access Journals (Sweden)

Ismail Adeniran

2011-12-01

Full Text Available The short QT syndrome (SQTS is a genetically heterogeneous condition characterized by abbreviated QT intervals and an increased susceptibility to arrhythmia and sudden death. This simulation study identifies arrhythmogenic mechanisms in the rapid-delayed rectifier K(+ current (I(Kr-linked SQT1 variant of the SQTS. Markov chain (MC models were found to be superior to Hodgkin-Huxley (HH models in reproducing experimental data regarding effects of the N588K mutation on KCNH2-encoded hERG. These ionic channel models were then incorporated into human ventricular action potential (AP models and into 1D and 2D idealised and realistic transmural ventricular tissue simulations and into a 3D anatomical model. In single cell models, the N588K mutation abbreviated ventricular cell AP duration at 90% repolarization (APD(90 and decreased the maximal transmural voltage heterogeneity (δV during APs. This resulted in decreased transmural heterogeneity of APD(90 and of the effective refractory period (ERP: effects that are anticipated to be anti-arrhythmic rather than pro-arrhythmic. However, with consideration of transmural heterogeneity of I(Kr density in the intact tissue model based on the ten Tusscher-Noble-Noble-Panfilov ventricular model, not only did the N588K mutation lead to QT-shortening and increases in T-wave amplitude, but δV was found to be augmented in some local regions of ventricle tissue, resulting in increased tissue vulnerability for uni-directional conduction block and predisposing to formation of re-entrant excitation waves. In 2D and 3D tissue models, the N588K mutation facilitated and maintained re-entrant excitation waves due to the reduced substrate size necessary for sustaining re-entry. Thus, in SQT1 the N588K-hERG mutation facilitates initiation and maintenance of ventricular re-entry, increasing the lifespan of re-entrant spiral waves and the stability of scroll waves in 3D tissue.

Máxima fase estável de lactato é ergômetro-dependente em modelo experimental utilizando ratos Máxima fase de estabilidad de lactato es ergómetro-dependiente en modelo experimental utilizando ratones The maximal lactate steady state is ergometer-dependent in experimental model using rats

Directory of Open Access Journals (Sweden)

Fúlvia de Barros Manchado

2006-10-01

Full Text Available A máxima fase estável de lactato (MFEL é considerada padrão-ouro para a determinação da intensidade de transição metabólica aeróbia-anaeróbia em exercício contínuo, porém a resposta lactacidêmica nessa intensidade é, em humanos, dependente do ergômetro utilizado na avaliação. Uma ferramenta importante para estudos em fisiologia e áreas correlatas é a aplicação de modelos experimentais utilizando animais. Entretanto, ainda são restritas as pesquisas destinadas a investigar protocolos de avaliação em ratos. O objetivo do estudo foi verificar se a MFEL é dependente do ergômetro utilizado para a avaliação aeróbia de ratos. Para isso, 40 ratos Wistar adultos foram avaliados em dois diferentes exercícios: natação e corrida em esteira. Em ambos, a MFEL foi verificada após aplicação de quatro testes contínuos, em diferentes intensidades, com duração de 25 minutos, separados por intervalo de 48 horas. Em todos os testes houve coleta sanguínea da cauda dos animais a cada cinco minutos de exercício para análise do lactato sanguíneo. Os testes de natação ocorreram em tanque cilíndrico profundo, com a temperatura da água a 31 ± 1°C. As cargas adotadas para os testes foram de 4,5; 5,0; 5,5; 6,0% do peso corporal, atadas ao dorso dos animais. Para a determinação da MFEL em corrida, houve seleção dos ratos corredores e as velocidades dos testes foram de 15, 20, 25, 30m.min¹. A MFEL foi interpretada como a mais alta intensidade de exercício na qual o aumento da lactacidemia foi igual ou inferior a 1mM, do 10º ao 25º minuto. Anova one-way identificou diferenças entre as concentrações de lactato sanguíneo nos diversos tempos de exercício e ergômetros. A MFEL na natação ocorreu a 5,0% do peso corporal (pc, em concentração de lactato de 5,20 ± 0,22mM. Para o exercício em esteira rolante, observou-se MFEL a 20m.min¹, em concentração 3,87 ± 0,33mM. Dessa forma, é possível concluir que a MFEL

Magnetic phase diagram of ErGe 1-xSi x (0

Science.gov (United States)

Thuéry, P.; El Maziani, F.; Clin, M.; Schobinger-Papamantellos, P.; Buschow, K. H. J.

1993-10-01

The composition-temperature magnetic phase diagram of ErGe 1- xSi x (0 0.40. For 0.17 ≥ x ≤ 0.55, a first-order transition occurs as function of the temperature between these two phases. For x ≥ 0.65, a lock-in transition takes place at TIC, leading from the wavevector ( k' x,0, k' z) to (1/2,0,1/2), as was already observed in ErSi. Finally, for x < 0.17 or 0.55 < x < 0.65, the wavevectors of the incommensurate phases characterized by (0,0, kz) or ( k' x,0, k' z) respectively remain unchanged in the whole temperature range below TN. For x≥0.65, a small amount of a magnetic phase characterized by the wavevector (0,0, 1/2) coexists with the main phases, below a Néel temperature T' N slightly lower than TN. In all cases, the erbium magnetic moments are colinear along the orthorhombic α-axis; the arrangement of the moments in the commensurate phases is the same as in ErSi and the incommensurate orderings correspond to sine-wave amplitude modulations. A brief account on the theoretical interpretation of this phase diagram is finally given.

Vabariigi Valitsuse istungitesaali mööbel = Furniture for the Estonian Government cabinet's meeting room

Index Scriptorium Estoniae

2008-01-01

Stenbocki Maja istungitesaali (Rahukohtu 3, Tallinn) mööbel. Disainerid: Katrin Vaikla, Argo Vaikla (Vaikla Disain), Liis Tarbe (Torpedo Interior OÜ). Argo ja Katrin Vaiklast, Vaikla Disaini tähtsamad tööd. Liis Tarbest, koostöös Vaikla Disainiga valminud tööd. 6 värv. vaadet, fotod sisearhitektidest

Expressed prostatic secretion biomarkers improve stratification of NCCN active surveillance candidates: performance of secretion capacity and TMPRSS2:ERG models.

Science.gov (United States)

Whelan, Christopher; Kawachi, Mark; Smith, David D; Linehan, Jennifer; Babilonia, Gail; Mejia, Rosa; Wilson, Timothy; Smith, Steven S

2014-01-01

Active surveillance is a viable patient option for prostate cancer provided that a clinical determination of low risk and presumably organ confined disease can be made. To standardize risk stratification schemes the NCCN (National Comprehensive Cancer Network®) provides guidelines for the active surveillance option. We determined the effectiveness of expressed prostatic secretion biomarkers for detecting occult risk factors in NCCN active surveillance candidates. Expressed prostatic secretion specimens were obtained before robot-assisted radical prostatectomy. Secretion capacity biomarkers, including total RNA and expressed prostatic secretion specimen volume, were measured by standard techniques. RNA expression biomarkers, including TXNRD1 mRNA, prostate specific antigen mRNA, TMPRSS2:ERG fusion mRNA and PCA3 mRNA, were measured by quantitative reverse-transcription polymerase chain reaction. Of the 528 patients from whom expressed prostatic secretions were collected 216 were eligible for active surveillance under NCCN guidelines. Variable selection on logistic regression identified 2 models, including one featuring types III and VI TMPRSS2:ERG variants, and one featuring 2 secretion capacity biomarkers. Of the 2 high performing models the secretion capacity model was most effective for detecting cases in this group that were up-staged or up-staged plus upgraded. It decreased the risk of up-staging in patients with a negative test almost eightfold and decreased the risk of up-staging plus upgrading about fivefold while doubling the prevalence of up-staging in the positive test group. Noninvasive expressed prostatic secretion testing may improve patient acceptance of active surveillance by dramatically reducing the presence of occult risk factors among those eligible for active surveillance under NCCN guidelines. Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Pädaste mõis pakub nii uut kui vana! / Aale Kask

Index Scriptorium Estoniae

Kask, Aale

2008-01-01

Renoveeritud Pädaste mõisa peahoonest (1875). Omanikud Imre Sooäär ja Martin Breuer. Mõisaansambli restaureerimine toimus aastail 1996-2008. Restaureerimisarhitekt Katrin Etverk. Sisearhitektuur: Imre Sooäär, Kärt Kukkur. Restoranisaal kasvab üle talveaiaks. Kärt Kukkuri, Katrin Etverki ja Ülle Grishakovi kommentaarid. Värv. välisvaade, 14 sisevaadet

Sirbi tegijad läbi aegade

Index Scriptorium Estoniae

2004-01-01

Toimetaja asetäitjad: Katrin Kivimaa, Reet Varblane jt. Kunst, arhitektuur: Alo Hoidre, Boris Lukats, Ressi Kaera, Jaak Olep, Ike Volkov, Mirjam Peil, Tiina Käesel, Katrin Kivimaa, Vappu Vabar, Reet Varblane, Mari Laaniste. Kunstnikud (arvutikujundus): Tõnu Soo, Ann Gornischeff, Gädvi Kuklase, Piia Ruber. Fotograafid: Solomon Rosenfeldt, Endel Köster, Kalju Suur, Arno Saar, Teet Malsroos

Priorities for research in miscarriage: a priority setting partnership between people affected by miscarriage and professionals following the James Lind Alliance methodology.

Science.gov (United States)

Prior, Matthew; Bagness, Carmel; Brewin, Jane; Coomarasamy, Arri; Easthope, Lucy; Hepworth-Jones, Barbara; Hinshaw, Kim; O'Toole, Emily; Orford, Julie; Regan, Lesley; Raine-Fenning, Nick; Shakespeare, Judy; Small, Rachel; Thornton, Jim; Metcalf, Leanne

2017-08-23

To identify and prioritise important research questions for miscarriage. A priority setting partnership using prospective surveys and consensus meetings following methods advocated by the James Lind Alliance. UK. Women and those affected by miscarriage working alongside healthcare professionals. In the initial survey, 1093 participants (932 women who have experienced miscarriage, 8 partners, 17 family members, friends or colleagues, 104 healthcare professionals and eight charitable organisations) submitted 3279 questions. A review of existing literature identified a further 64. Non-questions were removed, and the remaining questions were categorised and summarised into 58 questions. In an interim electronic survey, 2122 respondents chose their top 10 priorities from the 58 summary questions. The 25 highest ranked in the survey were prioritised at a final face-to-face workshop. In summary, the top 10 priorities were ranked as follows: research into preventative treatment, emotional aspects in general, investigation, relevance of pre-existing medical conditions, emotional support as a treatment, importance of lifestyle factors, importance of genetic and chromosomal causes, preconception tests, investigation after different numbers of miscarriage and male causal factors. These results should be the focus of future miscarriage research. Presently, studies are being conducted to address the top priority; however, many other priorities, especially psychological and emotional support, are less well researched areas. We hope our results will encourage both researchers and funders to focus on these priorities. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Evaluation of urinary prostate cancer antigen-3 (PCA3) and TMPRSS2-ERG score changes when starting androgen-deprivation therapy with triptorelin 6-month formulation in patients with locally advanced and metastatic prostate cancer

DEFF Research Database (Denmark)

Martínez-Piñeiro, Luis; Schalken, Jack A; Cabri, Patrick

2014-01-01

change at 6 months, according to baseline variables. Other outcome measures included urinary PCA3 and TMPRSS2-ERG scores and statuses, and serum testosterone and prostate-specific antigen (PSA) levels at baseline and at 1, 3 and 6 months after initiation of ADT. Safety was assessed by recording adverse......OBJECTIVE: To assess prostate cancer antigen-3 (PCA3) and TMPRSS2-ERG scores in patients with advanced and metastatic prostate cancer at baseline and after 6 months of treatment with triptorelin 22.5 mg, and analyse these scores in patient-groups defined by different disease characteristics....... PATIENTS AND METHODS: The Triptocare study was a prospective, open-label, multicentre, single-arm, Phase III study of triptorelin 22.5 mg in men with locally advanced or metastatic prostate cancer, who were naïve to androgen-deprivation therapy (ADT). The primary objective was to model the urinary PCA3...

Dune-slope activity due to frost and wind throughout the north polar erg, Mars.

Science.gov (United States)

Diniega, Serina; Hansen, Candice J; Allen, Amanda; Grigsby, Nathan; Li, Zheyu; Perez, Tyler; Chojnacki, Matthew

2017-01-01

Repeat, high-resolution imaging of dunes within the Martian north polar erg have shown that these dune slopes are very active, with alcoves forming along the dune brink each Mars year. In some areas, a few hundred cubic metres of downslope sand movement have been observed, sometimes moving the dune brink 'backwards'. Based on morphological and activity-timing similarities of these north polar features to southern dune gullies, identifying the processes forming these features is likely to have relevance for understanding the general evolution/modification of dune gullies. To determine alcove-formation model constraints, we have surveyed seven dune fields, each over 1-4 Mars winters. Consistent with earlier reports, we found that alcove-formation activity occurs during the autumn-winter seasons, before or while the stable seasonal frost layer is deposited. We propose a new model in which alcove formation occurs during the autumn, and springtime sublimation activity then enhances the feature. Summertime winds blow sand into the new alcoves, erasing small alcoves over a few Mars years. Based on the observed rate of alcove erasure, we estimated the effective aeolian sand transport flux. From this, we proposed that alcove formation may account for 2-20% of the total sand movement within these dune fields.

Elu koos loodusega / Ell-Maaja Randküla

Index Scriptorium Estoniae

Randküla, Ell-Maaja, 1939-2016

2005-01-01

Villa Harjumaal Viimsi vallas Miidurannas. Arhitekt Emil Urbel. Sisekujundus: Katrin Vaikla, Argo Vaikla, Tiina Teng, AS Vaikla Disain. Villa pälvis Eesti Sisearhitektide Liidu 2004. a. aastapreemia. Argo ja Katrin Vaiklast, AS Vaikla Disain tähtsamad tööd. Tiina Tengist, tema erialasest tegevusest. Liis Lindverest, tema tähtsamad tööd. Ill.: 3 plaani, 11 värv. vaadet

Comparação entre a utilização de saliva e sangue para determinação do lactato mínimo em cicloergômetro e ergômetro de braço em mesa-tenistas Comparacion entre la utilizacion de saliva y sangre para la determinacion del lactato mínimo en cicloergómetro y ergómetro de brazo en tenistas de mesa Comparison between the use of saliva and blood for the minimum lactate determination in arm ergometer and cycle ergometer in table tennis players

Directory of Open Access Journals (Sweden)

Alessandro Moura Zagatto

2004-12-01

Full Text Available O objetivo do estudo foi verificar a possibilidade de determinar o teste de lactato mínimo (TLM com concentrações de sódio (Na+, potássio (K+ e lactato (LAC na saliva em ergômetro de braço e cicloergômetro. Foram participantes deste estudo oito mesa-tenistas de nível internacional. Como estímulo anaeróbio no TLM em ambos os ergômetros foram utilizados testes máximos de 30 segundos. No ergômetro de braço isocinético (Cybex Ube 2432 foi aplicada a força máxima com rotação fixa em 102rpm e no cicloergômetro, aplicada a carga de 7,5% do peso corporal (Kp. Após o estímulo anaeróbio no ergômetro de braço, foi iniciado um teste incremental com rotações na manivela constante a 60rpm, iniciado a 49 watts com aumento de 16 watts a cada estágio de três minutos de exercício. A intensidade correspondente ao TLM foi determinado com amostras de sangue e saliva (LACmin braço; Na+min braço-saliva e K+min braço-saliva, respectivamente. Para o cicloergômetro, a carga inicial foi de 85 watts e aumento de 17 watts com rotação do pedal constante a 70rpm. Cada estágio de exercício também teve a duração de três minutos. O LACmin foi determinado utilizando amostras de sangue e saliva (LACmin ciclo; Na+min ciclo-saliva, K+min ciclo-saliva e LACmin ciclo-saliva, respectivamente. Em ambos os ergômetros, as intensidades obtidas no TLM foram correspondentes à derivada zero do ajuste polinomial entre metabólito versus intensidade. Foram utilizados, como procedimentos estatísticos, o teste ANOVA One Way, teste t de Student pareado e teste de correlação de Pearson com níveis de significância de 5%. Os LACmin determinados com amostras de sangue e de saliva, tanto para o ergômetro de braço (LACmin braço 91,71 ± 12,43; Na+min braço-saliva 71,99 ± 23,42; K+min braço-saliva 79,67 ± 17,72, quanto para cicloergômetro (LACmin ciclo 157,68 ± 13,48; LACmin ciclo-saliva 135,49 ± 33,2; Na+min ciclo-saliva 121,81 ± 51,31; K

Utilização do questionário ERG na avaliação do grau de satisfação dos pacientes submetidos à otoplastia em um serviço de residência médica de otorrinolaringologia Using ERG inquiry to evaluate otoplasty satisfaction in an otorhinolaryngology medical residency training hospital

Directory of Open Access Journals (Sweden)

Silvio Antonio Monteiro Marone

2012-02-01

Full Text Available A importância da intervenção cirúrgica em diminuir o sofrimento psicológico e melhorar a autoestima em pacientes com deformidades auriculares já está bem documentada. As pesquisas têm focado nos resultados das terapias com ênfase no paciente, observando principalmente satisfação, resultado funcional e impacto na qualidade de vida. Quantificar alterações na qualidade de vida tem sido um desafio. O uso de inquéritos válidos, a exemplo da Escala de Resultados de Glasgow (ERG, auxiliam na obtenção dos dados. OBJETIVO: Avaliar o impacto na qualidade de vida dos pacientes submetidos à otoplastia realizada em serviço de residência médica, utilizando como base a ERG, bem como sua funcionalidade. CASUÍSTICA E MÉTODOS: Estudo retrospectivo incluindo pacientes submetidos à otoplastia entre julho de 2009 e julho de 2010. Os dados foram coletados por meio de questionário oferecido ao paciente no retorno pós-operatório. RESULTADOS: Trinta e seis pacientes responderam ao questionário. Houve aumento na qualidade de vida, demonstrado pelas medianas positivas obtidas pelo questionário. Não houve diferença significativa quanto aos valores obtidos entre os sexos e entre diferentes faixas etárias. CONCLUSÃO: Os pacientes mostraram-se satisfeitos com o resultado pós-operatório. Houve aumento de qualidade de vida, conforme demonstrado pelos resultados positivos. A ERG pareceu-nos fácil e elucidativa.The ear deformity surgery intervention impact on psychological and self-esteem aspects, in adults and children, is well documented. Recently, the studys are focused on patient satisfaction, funcional result and impact on quality of life. Any modification on patient's quality of life has been a challenge. The use of valid and established questionnairies, like Glasgow Benefit Inventory (GBI, assists on data analyse, turning it consistent. AIM: The aim of this study is to evaluate the impact on patients quality of life after otoplasty

Fortalecimiento del sector de la soldadura en la Provincia de Santa Elena a través de actividades del Centro de Capacitación de Soldadura LINDE-UPSE

Directory of Open Access Journals (Sweden)

Jorge Lucin

2015-10-01

Abstract The generation of grands projects that the country has, in its execution bears the important contribution of technical work such as welding. The University Santa Elena Peninsula, UPSE and multinational LINDE, ex AGA S.A.,  in order to strengthen the area of welding work in the province of Santa Elena, have signed a cooperation agreement with a duration of 5 years. For this purpose, is installed, an Training Center first order with equipment, machinery, tooling and supplies needed to offer quality work. Physical resources are given to UPSE, while knowledge and technique gives the multinational facilitator through highly qualified instructor.  The courses   to offering are approbation. The work is organized upon circulation, registration, training, evaluation, approval and final reports for each course, which is based on the statistics and media documents. Thus, over the first 3 years of work, has trained 229 people, with a total of 240 hours in 12 basic curs for welders support. Representative institutions in these works have been favored by updating technical knowledge and taught at the Center. The agreement remaining 1.5 years to finish but given its fruitful work, surely renew contributions towards this important technical work such as welding.

DNA repair genes RAD52 and SRS2, a cell wall synthesis regulator gene SMI1, and the membrane sterol synthesis scaffold gene ERG28 are important in efficient Agrobacterium-mediated yeast transformation with chromosomal T-DNA.

Science.gov (United States)

Ohmine, Yuta; Satoh, Yukari; Kiyokawa, Kazuya; Yamamoto, Shinji; Moriguchi, Kazuki; Suzuki, Katsunori

2016-04-02

Plant pathogenic Agrobacterium strains can transfer T-DNA regions of their Ti plasmids to a broad range of eukaryotic hosts, including fungi, in vitro. In the recent decade, the yeast Saccharomyces cerevisiae is used as a model host to reveal important host proteins for the Agrobacterium-mediated transformation (AMT). Further investigation is required to understand the fundamental mechanism of AMT, including interaction at the cell surface, to expand the host range, and to develop new tools. In this study, we screened a yeast mutant library for low AMT mutant strains by advantage of a chromosome type T-DNA, which transfer is efficient and independent on integration into host chromosome. By the mutant screening, we identified four mutant strains (srs2Δ, rad52Δ, smi1Δ and erg28Δ), which showed considerably low AMT efficiency. Structural analysis of T-DNA product replicons in AMT colonies of mutants lacking each of the two DNA repair genes, SRS2 and RAD52, suggested that the genes act soon after T-DNA entry for modification of the chromosomal T-DNA to stably maintain them as linear replicons and to circularize certain T-DNA simultaneously. The cell wall synthesis regulator SMI1 might have a role in the cell surface interaction between the donor and recipient cells, but the smi1Δ mutant exhibited pleiotropic effect, i.e. low effector protein transport as well as low AMT for the chromosomal T-DNA, but relatively high AMT for integrative T-DNAs. The ergosterol synthesis regulator/enzyme-scaffold gene ERG28 probably contributes by sensing a congested environment, because growth of erg28Δ strain was unaffected by the presence of donor bacterial cells, while the growth of the wild-type and other mutant yeast strains was suppressed by their presence. RAD52 and the DNA helicase/anti-recombinase gene SRS2 are necessary to form and maintain artificial chromosomes through the AMT of chromosomal T-DNA. A sterol synthesis scaffold gene ERG28 is important in the high

Recent Trends in Thinking about Warfare

Science.gov (United States)

2006-09-01

34 Marine Corps Gazette, Oct 1989, pp. 22-26. 2. William S. Lind, "FMFM 1 A: Fourth Generation War," http://www.d-n- i.net/lind/4gw manual draft 3 revised...break the enemy’s will to continue. 106.Indeed, Lind’s so-called " manual " for 4GW (FMFM, cited earlier), focuses almost entirely on insurgency, thus...File, "Posse Comitatus Act," htp :/ /www.uscg.mil /hq /g-cp /comrel /factfile /Factcards /PosseComita- tus.html; and Gary Felicetti and John Luce, "The

Unicorn

OpenAIRE

K. Jivkova

2012-01-01

This article contains five short poems. The author, Katrin Jivkova (10), is Bulgarian but lives in the UK. She will be in year 6 in September. From a very early age Katrin has been dreaming of becoming a writer. She has already written many short stories and these are her first attempts at writing poetry. The poems are inspired by frightening stories that are popular among children of her age and keep them awake at nights.

Unicorn

Directory of Open Access Journals (Sweden)

K. Jivkova

2012-09-01

Full Text Available This article contains five short poems. The author, Katrin Jivkova (10, is Bulgarian but lives in the UK. She will be in year 6 in September. From a very early age Katrin has been dreaming of becoming a writer. She has already written many short stories and these are her first attempts at writing poetry. The poems are inspired by frightening stories that are popular among children of her age and keep them awake at nights.

First complete genome sequence of a species in the genus Microterricola, an extremophilic cold active enzyme producing bacterial strain ERGS5:02 isolated from Sikkim Himalaya.

Science.gov (United States)

Himanshu; Swarnkar, Mohit Kumar; Singh, Dharam; Kumar, Rakshak

2016-03-20

Here, we report the first ever complete genome sequence of any species in the genus Microterricola. The bacterium Microterricola viridarii ERGS5:02 isolated from the glacial stream of Sikkim Himalaya survived at low temperature and exhibited enhanced growth upon UV treatment, in addition, it also produced cold active enzymes. The complete genome assembly of 3.7 Mb suggested for the presence of genetic elements favoring the survival of bacterium under extreme conditions of UV and low temperature besides producing amylase, lipase and protease of industrial relevance. Copyright © 2016 Elsevier B.V. All rights reserved.

Acute alteration of cardiac ECG, action potential, I{sub Kr} and the human ether-a-go-go-related gene (hERG) K{sup +} channel by PCB 126 and PCB 77

Energy Technology Data Exchange (ETDEWEB)

Park, Mi-Hyeong; Park, Won Sun; Jo, Su-Hyun, E-mail: suhyunjo@kangwon.ac.kr

2012-07-01

Polychlorinated biphenyls (PCBs) have been known as serious persistent organic pollutants (POPs), causing developmental delays and motor dysfunction. We have investigated the effects of two PCB congeners, 3,3′,4,4′-tetrachlorobiphenyl (PCB 77) and 3,3′,4,4′,5-pentachlorobiphenyl (PCB 126) on ECG, action potential, and the rapidly activating delayed rectifier K{sup +} current (I{sub Kr}) of guinea pigs' hearts, and hERG K{sup +} current expressed in Xenopus oocytes. PCB 126 shortened the corrected QT interval (QTc) of ECG and decreased the action potential duration at 90% (APD{sub 90}), and 50% of repolarization (APD{sub 50}) (P < 0.05) without changing the action potential duration at 20% (APD{sub 20}). PCB 77 decreased APD{sub 20} (P < 0.05) without affecting QTc, APD{sub 90}, and APD{sub 50}. The PCB 126 increased the I{sub Kr} in guinea-pig ventricular myocytes held at 36 °C and hERG K{sup +} current amplitude at the end of the voltage steps in voltage-dependent mode (P < 0.05); however, PCB 77 did not change the hERG K{sup +} current amplitude. The PCB 77 increased the diastolic Ca{sup 2+} and decreased Ca{sup 2+} transient amplitude (P < 0.05), however PCB 126 did not change. The results suggest that PCB 126 shortened the QTc and decreased the APD{sub 90} possibly by increasing I{sub Kr}, while PCB 77 decreased the APD{sub 20} possibly by other modulation related with intracellular Ca{sup 2+}. The present data indicate that the environmental toxicants, PCBs, can acutely affect cardiac electrophysiology including ECG, action potential, intracellular Ca{sup 2+}, and channel activity, resulting in toxic effects on the cardiac function in view of the possible accumulation of the PCBs in human body. -- Highlights: ► PCBs are known as serious environmental pollutants and developmental disruptors. ► PCB 126 shortened QT interval of ECG and action potential duration. ► PCB 126 increased human ether-a-go-go-related K{sup +} current and I{sub Kr}. �

糖尿病视网膜1期病变多焦视网膜图变化分析%A Study in the Changes of mfERG in Stage 1 Diabetic Retinopathyn

Institute of Scientific and Technical Information of China (English)

张聪; 刘哲丽; 徐丽; 郭敬斌

2009-01-01

目的 通过检测糖尿病视网膜1期病变患者多焦视网膜电图(multifocal electroretino-gram,mfERG),评价1期糖尿病视网膜病变患者早期视功能的变化.方法 检测正常对照组31只眼,1期糖尿病视网膜病变组46只眼的mtERG在视野30°的测试范围内6个不同离心度的环形区N1、P1波潜伏期、P1波反应密度改变.结果 在视野30°的测试范围内6个不同离心度的环形区,1期糖尿病视网膜病变组(DR组)与正常对照组之间比较N1、P1波潜伏期显著延长;环1、2区DR组与正常对照组之间比较P1波反应密度显著降低.结论 尚未出现肉眼可见眼底改变的1期糖尿病视网膜病变即可出现视功能的异常,mfERG能够定量的检测1期糖尿病视网膜病变的局部视功能变化,为糖尿病视网膜病变的早期诊断提供有效方法.%Objective To investigate the changes of retinal function in stage 1 of diabetic retinopathy detected by multifoeal electroretinogram (mfERG).Methods The responses of mfERG were recorded and analyzed from eyes of 31 normal control subjects and 46 diabetic patients with stage 1 of diabetic retinopathy. Results In eyes of diabetic patients with stage 1 of diabetic retinopathy (DR), the lateneies of N1, P1 were delayed obviously compared to normal control subjects, in the field of about 30 degrees of six rings with different eccentricities; the response densities of the P1 ring1, 2 was significantly decreased in diabetic patients with stagel of diabetic retinopathy compared to normal control subjects.Conclusions The abnormalities of retinal function may occur in stagel of diabetic retinopathy, when there is no abnormality of ocular fundus.As a new objective and quantitative examination for visual function, mfERG may be valuable in early diagnosis of diabetic retinopathy.

Soutien institutionnel à des organismes de recherche sur les ...

International Development Research Centre (IDRC) Digital Library (Canada)

Asie du Sud (le Bangladesh, l'Inde, le Népal, le Pakistan et le Sri Lanka). Parmi les 16 demandeurs d'Asie du Sud retenus, neuf viennent de l'Inde. La recherche sur les politiques en Asie du Sud s'effectue principalement en Inde, forte d'une ...

Environmental contaminants in oil field produced waters discharged into wetlands

International Nuclear Information System (INIS)

Ramirez, P. Jr.

1994-01-01

The 866-acre Loch Katrine wetland complex in Park County, Wyoming provides habitat for many species of aquatic birds. The complex is sustained primarily by oil field produced waters. This study was designed to determine if constituents in oil field produced waters discharged into Custer Lake and to Loch Katrine pose a risk to aquatic birds inhabiting the wetlands. Trace elements, hydrocarbons and radium-226 concentrations were analyzed in water, sediment and biota collected from the complex during 1992. Arsenic, boron, radium-226 and zinc were elevated in some matrices. The presence of radium-226 in aquatic vegetation suggests that this radionuclide is available to aquatic birds. Oil and grease concentrations in water from the produced water discharge exceeded the maximum 10 mg/l permitted by the WDEQ (1990). Total aliphatic and aromatic hydrocarbon concentrations in sediments were highest at the produced water discharge, 6.376 μg/g, followed by Custer Lake, 1.104 μg/g. The higher levels of hydrocarbons found at Custer Lake, compared to Loch Katrine, may be explained by Custer Lake's closer proximity to the discharge. Benzo(a)pyrene was not detected in bile from gadwalls collected at Loch Katrine but was detected in bile from northern shovelers collected at Custer Lake. Benzo(a)pyrene concentrations in northern shoveler bile ranged from 500 to 960 ng/g (ppb) wet weight. The presence of benzo(a)pyrene in the shovelers indicates exposure to petroleum hydrocarbons

BIOLOGICAL AND ENVIRONMENTAL PECULIARITIES OF INTRODUCTION OF WASHINGTONIA FILIFERA (LIND. EX ANDR. H. WENDL. EX BARY AT THE SOUTHERN COAST OF CRIMEA

Directory of Open Access Journals (Sweden)

Yuriy V. Plugatar

2018-01-01

Full Text Available Abstract. Aim of this research is to study winter resistance, drought resistance, resistance to fungal diseases and harmful insects of Washingtonia filifera (Lind. ex Andr., H. Wendl. ex A. Bary, 1879 and to examine the possibility of the subsequent selection using the experimental mutagenesis for increasing its frost resistance at the Southern Coast of the Crimea (SCC. Material and methods. The material and objects of our research were the collection plantations of Washingtonia filifera in the Arboretum of Nikitsky Botanical Garden (NBG and parks of the South Coast of Crimea. Research methods: comparative-ecological, biometric, analytical and visual. To achieve the objective, the following results were obtained in the course of the studies. The history of introduction of this species in the NBG has been described and its occurrence at the Southern Coast of the Crimea (SCC shown. An analysis of the quantitative biometric indicators of the leaves’ growth and die-back on average over the vegetation period on the basis of phenological observations over the test plants has been carried out taking into consideration the existing agricultural background. The reasons and factors influencing the frost resistance of this species depending on the combination of the set of meteorological indicators causing a certain level of frosting depending not only on the minimum negative temperatures but also on the soil and atmospheric moisture have been identified. Thresholds values of the impact of extreme negative temperatures for the Washingtonia filifera at the lethal and sub-lethal levels have been identified. Danger of infection of the representatives of the Arecaceae family (Arecaceae C.H. Schultz with the new types of dangerous phytophages has been identified. The possibility of its selection with the use of a mutagen – colchicine has been shown. Main conclusions. The criteria have been outlined which will give the opportunity in the future to provide

Journal of Biosciences | Indian Academy of Sciences

Indian Academy of Sciences (India)

Home; Journals; Journal of Biosciences. Marta Linde-Medina. Articles written in Journal of Biosciences. Volume 36 Issue 4 September 2011 pp 575-585 Brief communication. Adaptation or exaptation? The case of the human hand · Marta Linde-Medina · More Details Abstract Fulltext PDF. A controversy of relevance to the ...

An extension of uncertainty management theory to the self : The relationship between justice, social comparison orientation, and antisocial work behaviors

NARCIS (Netherlands)

Thau, Stefan; Aquino, Karl; Wittek, Rafael; Aquino, 27021

A multisource field study of 103 employees and their supervisors tested an extension of uncertainty management theory (E. A. Lind & K. Van den Bos, 2002; K. Van den Bos & E. A. Lind, 2002). According to this theory, persons high in social comparison orientation (F. X. Gibbons & B. P. Buunk, 1999)

Exploring the challenge of health research priority setting in partnership: reflections on the methodology used by the James Lind Alliance Pressure Ulcer Priority Setting Partnership.

Science.gov (United States)

Madden, Mary; Morley, Richard

2016-01-01

The James Lind Alliance (JLA) brings patients, carers and clinicians together in Priority Setting Partnerships (PSPs) to identify and prioritise shared uncertainties about the effects of treatment. The JLA emerged from the evidence-informed healthcare movement to address a concern that the research being carried out on treatment effectiveness is not that of most importance to patients and health professionals. In the JLA PSPs, 'hard' evidence-informed ideals meet 'soft' participatory practices. This article explores the challenges of putting co-production methods into practice by reflecting on the methods used by the JLA Pressure Ulcer PSP (JLAPUP). The JLA principles are transparency, inclusivity and avoiding waste in research. This means paying the same close critical attention to how PSPs are designed and run, as is desired in the health research which the JLA seeks to influence. JLAPUP showed that it was possible to work in partnership in a field where patients are often elderly, immobile, unrepresented and particularly unwell, many of whom are living with more than one long term condition. However, for those unfamiliar with it, 'uncertainty' was a difficult term to get to grips with. Also, it was harder for some people than others to take part and to have their voices heard and understood. In keeping with other PSPs, JLAPUP found that the nature and quality of research into pressure ulcer prevention and treatment did not reflect the priorities of those who took part. ᅟ. Studies identifying a mismatch between the priorities of academics and clinicians and those of people with direct experience of a health condition pose a challenge to the assumption that professional researchers can represent the interests of patients and the public in setting priorities for health research. The James Lind Alliance (JLA) brings patients, carers and clinicians together in Priority Setting Partnerships (PSPs) to identify and prioritise shared uncertainties about the effects of

L’évaluation, un outil de l’ergonome pour transformer le contexte d’intervention Evaluation, a tool of ergonomists for changing the intervention context La evaluación, una herramienta del ergónomo para transformar el contexto de la intervención

Directory of Open Access Journals (Sweden)

Aurélie Landry

2010-05-01

ón-evaluativa permite identificar los factores favorables a una intervención e instruir las hipótesis de los ergónomos que intervienen sobre las relaciones entre el proceso de intervención y los resultados obtenidos. Los casos utilizados ilustran como la investigación evaluativa puede permitir al ergónomo mejorar las condiciones en las cuales él interviene, compartiendo los indicadores sobre el desarrollo del proyecto. Comunicando, en el curso de la acción, a otros actores del proyecto los indicadores de gestión de la intervención, el ergónomo modifica el contexto en el cual interviene. Utilizando los indicadores de resultados, el ergónomo puede mostrar los aportes de la acción. Igualmente el ergónomo busca adaptar mejor sus métodos teniendo en cuenta los aspectos favorables así como los obstáculos presentes en el contexto de la acción.

Isikult vabaduse võtmine põhjendusel, et ta on psüühikahäire tõttu endale või teistele ohtlik / Sten Lind, Katrin Eino

Index Scriptorium Estoniae

Lind, Sten, 1979-

2014-01-01

Psüühikahäire määratlemine ning isiku ohtlikkus psühhiaatrilise abi seaduse § 11, sotsiaalhoolekande seaduse § 19 ja karistusseadustiku § 86 kontekstis. Riigikohtu lahenditest 3-2-1-81-07 ja 3-2-1-155-13

Setting the top 10 research priorities to improve the health of people with Type 2 diabetes: a Diabetes UK-James Lind Alliance Priority Setting Partnership.

Science.gov (United States)

Finer, S; Robb, P; Cowan, K; Daly, A; Shah, K; Farmer, A

2018-07-01

To describe processes and outcomes of a priority setting partnership to identify the 'top 10 research priorities' in Type 2 diabetes, involving people living with the condition, their carers, and healthcare professionals. We followed the four-step James Lind Alliance Priority Setting Partnership process which involved: gathering uncertainties using a questionnaire survey distributed to 70 000 people living with Type 2 diabetes and their carers, and healthcare professionals; organizing the uncertainties; interim priority setting by resampling of participants with a second survey; and final priority setting in an independent group of participants, using the nominal group technique. At each step the steering group closely monitored and guided the process. In the first survey, 8227 uncertainties were proposed by 2587 participants, of whom 18% were from black, Asian and minority ethnic groups. Uncertainties were formatted and collated into 114 indicative questions. A total of 1506 people contributed to a second survey, generating a shortlist of 24 questions equally weighted to the contributions of people living with diabetes and their carers and those of healthcare professionals. In the final step the 'top 10 research priorities' were selected, including questions on cure and reversal, risk identification and prevention, and self-management approaches in Type 2 diabetes. Systematic and transparent methodology was used to identify research priorities in a large and genuine partnership of people with lived and professional experience of Type 2 diabetes. The top 10 questions represent consensus areas of research priority to guide future research, deliver responsive and strategic allocation of research resources, and improve the future health and well-being of people living with, and at risk of, Type 2 diabetes. © 2018 The Authors. Diabetic Medicine published by John Wiley & Sons Ltd on behalf of Diabetes UK.

'Den danske model' som tema

DEFF Research Database (Denmark)

Caraker, Emmett; Juul, Ida; Klindt, Mads Peter

2012-01-01

Tidsskrift for Arbejdsliv vol. 14, nr. 2, 5-8. Tema: 'Den danske model'. Redigeret af Emmett Caraker, Ida Juul, Mads peter Klindt & Jens Lind. 2011. København. 128 s.......Tidsskrift for Arbejdsliv vol. 14, nr. 2, 5-8. Tema: 'Den danske model'. Redigeret af Emmett Caraker, Ida Juul, Mads peter Klindt & Jens Lind. 2011. København. 128 s....

Water as a Human Right for the Middle East and North Africa | CRDI ...

International Development Research Centre (IDRC) Digital Library (Canada)

11 juil. 2008 ... Le CRDI investit dans des solutions locales aux problèmes auxquels l'Inde est confrontée, comme le stress thermique, la gestion de l'eau et les migrations liées aux changements climatiques. Voir davantage Le CRDI aide l'Inde à s'adapter aux changements climatiques au moyen de données probantes, ...

Identifying trial recruitment uncertainties using a James Lind Alliance Priority Setting Partnership - the PRioRiTy (Prioritising Recruitment in Randomised Trials) study.

Science.gov (United States)

Healy, Patricia; Galvin, Sandra; Williamson, Paula R; Treweek, Shaun; Whiting, Caroline; Maeso, Beccy; Bray, Christopher; Brocklehurst, Peter; Moloney, Mary Clarke; Douiri, Abdel; Gamble, Carrol; Gardner, Heidi R; Mitchell, Derick; Stewart, Derek; Jordan, Joan; O'Donnell, Martin; Clarke, Mike; Pavitt, Sue H; Guegan, Eleanor Woodford; Blatch-Jones, Amanda; Smith, Valerie; Reay, Hannah; Devane, Declan

2018-03-01

Despite the problem of inadequate recruitment to randomised trials, there is little evidence to guide researchers on decisions about how people are effectively recruited to take part in trials. The PRioRiTy study aimed to identify and prioritise important unanswered trial recruitment questions for research. The PRioRiTy study - Priority Setting Partnership (PSP) included members of the public approached to take part in a randomised trial or who have represented participants on randomised trial steering committees, health professionals and research staff with experience of recruiting to randomised trials, people who have designed, conducted, analysed or reported on randomised trials and people with experience of randomised trials methodology. This partnership was aided by the James Lind Alliance and involved eight stages: (i) identifying a unique, relevant prioritisation area within trial methodology; (ii) establishing a steering group (iii) identifying and engaging with partners and stakeholders; (iv) formulating an initial list of uncertainties; (v) collating the uncertainties into research questions; (vi) confirming that the questions for research are a current recruitment challenge; (vii) shortlisting questions and (viii) final prioritisation through a face-to-face workshop. A total of 790 survey respondents yielded 1693 open-text answers to 6 questions, from which 1880 potential questions for research were identified. After merging duplicates, the number of questions was reduced to 496. Questions were combined further, and those that were submitted by fewer than 15 people and/or fewer than 6 of the 7 stakeholder groups were excluded from the next round of prioritisation resulting in 31 unique questions for research. All 31 questions were confirmed as being unanswered after checking relevant, up-to-date research evidence. The 10 highest priority questions were ranked at a face-to-face workshop. The number 1 ranked question was "How can randomised trials become

Esofagomanometria e phmetria de 24 horas para avaliar a fundoplicatura de lind laparoscópica na doença do refluxo gastroesofágico

Directory of Open Access Journals (Sweden)

Pablo Roberto Miguel

Full Text Available As técnicas laparoscópicas e toracoscópicas proporcionaram uma nova dimensão para a correção dos distúrbios funcionais do esôfago. O sucesso terapêutico, entretanto, depende da confirmação da doença esofágica como causa dos sintomas, da compreensão da causa básica da disfunção e da identificação do paciente cirúrgico. O presente trabalho é um estudo retrospectivo em pacientes operados pela técnica de Lind para doença do refluxo gastroesofágico (DRGE. Tem por objetivo estabelecer o valor do uso sistemático da esofagomanometria e da pHmetria de 24 horas na seleção de pacientes e na avaliação funcional pré e pós-operatória. Quarenta e um pacientes (68,3% tinham hipotonia do esfíncter inferior do esôfago. A pressão foi em média de 9,2 mmHg no pré-operatório e de 15,2mmHg no pós-operatório, com um aumento de 6,0 mmHg. Este aumento foi de 8,8mmHg nos hipotônicos e 4,3 mmHg nos normotônicos. Houve algum grau de hipomotilidade do corpo do esôfago em 14 pacientes (23,3%, sendo que, deste grupo, quatro (28,5% obtiveram melhora pós-operatória. Refluxo ácido patológico foi constatado em 51 casos (85,0% pela pHmetria. A média do score de DeMeester pré-operatório foi de 31,4, baixando depois para 3,2. A esofagomanometria e a pHmetria de 24 horas são métodos eficazes em revelar o nível de modificação funcional estabelecido pela cirurgia anti-refluxo e ajudam objetivamente na seleção.

Detection of Gene Rearrangements in Circulating Tumor Cells: Examples of ALK-, ROS1-, RET-Rearrangements in Non-Small-Cell Lung Cancer and ERG-Rearrangements in Prostate Cancer.

Science.gov (United States)

Catelain, Cyril; Pailler, Emma; Oulhen, Marianne; Faugeroux, Vincent; Pommier, Anne-Laure; Farace, Françoise

2017-01-01

Circulating tumor cells (CTCs) hold promise as biomarkers to aid in patient treatment stratification and disease monitoring. Because the number of cells is a critical parameter for exploiting CTCs for predictive biomarker's detection, we developed a FISH (fluorescent in situ hybridization) method for CTCs enriched on filters (filter-adapted FISH [FA-FISH]) that was optimized for high cell recovery. To increase the feasibility and reliability of the analyses, we combined fluorescent staining and FA-FISH and developed a semi-automated microscopy method for optimal FISH signal identification in filtration-enriched CTCs . Here we present these methods and their use for the detection and characterization of ALK-, ROS1-, RET-rearrangement in CTCs from non-small-cell lung cancer and ERG-rearrangements in CTCs from prostate cancer patients.

Medium-Energy Particle experiments (MEPs) for the Exploration of energization and Radiation in Geospace (ERG) mission

Science.gov (United States)

Kasahara, S.; Yokota, S.; Mitani, T.; Asamura, K.; Hirahara, M.; Shibano, Y.; Yamamoto, K.; Takashima, T.

2017-12-01

ERG (Exploration of energization and Radiation in Geospace) is the geospace exploration spacecraft, which was launched on 20 December 2016. The mission goal is to unveil the physics behind the drastic radiation belt variability during space storms. One of key observations is the measurement of ions and electrons in the medium-energy range (10-200 keV), since these particles excite EMIC, magnetosonic, and whistler waves, which are theoretically suggested to play significant roles in the relativistic electron acceleration and loss. Medium-Energy Particle experiments - electron analyser (MEP-e) measures the energy and the direction of each incoming electron in the range of 7 to 87 keV. The sensor covers 2π radian disk-like field-of-view with 16 detectors, and the solid angle coverage is achieved by using spacecraft spin motion. The electron energy is independently measured by an electrostatic analyser and avalanche photodiodes, enabling the significant background reduction. Medium-Energy Particle experiments - ion mass analyzer (MEP-i) measures the energy, mass, and charge state of the direction of each incoming ion in the medium-energy range (180 keV/q). MEP-i thus provides the velocity distribution functions of medium-energy ions (e.g., protons and oxygens), from which we can obtain significant information on local ion energization and pitch angle scattering in the inner magnetosphere. Heavy ion measurements can also play an important role to restrict global mass transport including the ionosphere and the plasmasheet. Here we show the technical approaches, data output, and highlights of initial observations.

Final scientific and technical report: New experiments to measure the neutrino mass scale

Energy Technology Data Exchange (ETDEWEB)

Monreal, Benjamin [Univ. of California, Santa Barbara, CA (United States)

2016-11-19

In this work, we made material progress towards future measurements of the mass of the neutrino. The neutrino is a fundamental particle, first observed in the 1950s and subjected to particularly intense study over the past 20 years. It is now known to have some, non-zero mass, but we are in an unusual situation of knowing the mass exists but not knowing what value it takes. The mass may be determined by precise measurements of certain radioactive decay distributions, particularly the beta decay of tritium. The KATRIN experiment is an international project which is nearing the beginning of a tritium measurement campaign using a large electrostatic spectrumeter. This research included participation in KATRIN, including construction and delivery of a key calibration subsystem, the ``Rear Section''. To obtain sensitivity beyond KATRIN's, new techniques are required; this work included R&D on a new technique we call CRES (Cyclotron Resonance Electron Spectroscopy) which has promise to enable even more sensitive tritium decay measurements. We successfully carried out CRES spectroscopy in a model system in 2014, making an important step towards the design of a next-generation tritium experiment with new neutrino mass measurement abilities.

Homeland Security: Developing National Doctrine to Guide State Strategy Development

Science.gov (United States)

2012-03-01

James Monroe in 1823 ( Martin , n.d.). There is also political doctrine, such as egalitarianism a “political doctrine that holds that all people...be able to engage a larger stakeholder community and avoid the need for a huge new bureaucracy (Linde, O’Brien, Lindstrom , Spiegeleire, Vayrynen...Presentation, Osan Air Force Base, South Korea. 74 Linde, E., O’Brien, K., Lindstrom , G., Spiegeleire, S., Vayrynen, M., & de Vries, H. (2002

Two missense mutations, E123Q and K151E, identified in the ERG11 allele of an azole-resistant isolate of Candida kefyr recovered from a stem cell transplant patient for acute myeloid leukemia

Directory of Open Access Journals (Sweden)

Célia Couzigou

2014-07-01

Full Text Available We report on the first cloning and nucleotide sequencing of an ERG11 allele from a clinical isolate of Candida kefyr cross-resistant to azole antifungals. It was recovered from a stem cell transplant patient, in an oncohematology unit exhibiting unexpected high prevalence of C. kefyr. Two amino acid substitutions were identified: K151E, whose role in fluconazole resistance was already demonstrated in Candida albicans, and E123Q, a new substitution never described so far in azole-resistant Candida yeast.

Identifying research priorities in anaesthesia and perioperative care: final report of the joint National Institute of Academic Anaesthesia/James Lind Alliance Research Priority Setting Partnership.

Science.gov (United States)

Boney, Oliver; Bell, Madeline; Bell, Natalie; Conquest, Ann; Cumbers, Marion; Drake, Sharon; Galsworthy, Mike; Gath, Jacqui; Grocott, Michael P W; Harris, Emma; Howell, Simon; Ingold, Anthony; Nathanson, Michael H; Pinkney, Thomas; Metcalf, Leanne

2015-12-16

To identify research priorities for Anaesthesia and Perioperative Medicine. Prospective surveys and consensus meetings guided by an independent adviser. UK. 45 stakeholder organisations (25 professional, 20 patient/carer) affiliated as James Lind Alliance partners. First 'ideas-gathering' survey: Free text research ideas and suggestions. Second 'prioritisation' survey: Shortlist of 'summary' research questions (derived from the first survey) ranked by respondents in order of priority. Final 'top ten': Agreed by consensus at a final prioritisation workshop. First survey: 1420 suggestions received from 623 respondents (49% patients/public) were refined into a shortlist of 92 'summary' questions. Second survey: 1718 respondents each nominated up to 10 questions as research priorities. Top ten: The 25 highest-ranked questions advanced to the final workshop, where 23 stakeholders (13 professional, 10 patient/carer) agreed the 10 most important questions: ▸ What can we do to stop patients developing chronic pain after surgery? ▸ How can patient care around the time of emergency surgery be improved? ▸ What long-term harm may result from anaesthesia, particularly following repeated anaesthetics?▸ What outcomes should we use to measure the 'success' of anaesthesia and perioperative care? ▸ How can we improve recovery from surgery for elderly patients? ▸ For which patients does regional anaesthesia give better outcomes than general anaesthesia? ▸ What are the effects of anaesthesia on the developing brain? ▸ Do enhanced recovery programmes improve short and long-term outcomes? ▸ How can preoperative exercise or fitness training, including physiotherapy, improve outcomes after surgery? ▸ How can we improve communication between the teams looking after patients throughout their surgical journey? Almost 2000 stakeholders contributed their views regarding anaesthetic and perioperative research priorities. This is the largest example of patient and public

Benchmarking the ERG valve tip and MRI Interventions Smart Flow neurocatheter convection-enhanced delivery system's performance in a gel model of the brain: employing infusion protocols proposed for gene therapy for Parkinson's disease

Science.gov (United States)

Sillay, Karl; Schomberg, Dominic; Hinchman, Angelica; Kumbier, Lauren; Ross, Chris; Kubota, Ken; Brodsky, Ethan; Miranpuri, Gurwattan

2012-04-01

Convection-enhanced delivery (CED) is an advanced infusion technique used to deliver therapeutic agents into the brain. CED has shown promise in recent clinical trials. Independent verification of published parameters is warranted with benchmark testing of published parameters in applicable models such as gel phantoms, ex vivo tissue and in vivo non-human animal models to effectively inform planned and future clinical therapies. In the current study, specific performance characteristics of two CED infusion catheter systems, such as backflow, infusion cloud morphology, volume of distribution (mm3) versus the infused volume (mm3) (Vd/Vi) ratios, rate of infusion (µl min-1) and pressure (mmHg), were examined to ensure published performance standards for the ERG valve-tip (VT) catheter. We tested the hypothesis that the ERG VT catheter with an infusion protocol of a steady 1 µl min-1 functionality is comparable to the newly FDA approved MRI Interventions Smart Flow (SF) catheter with the UCSF infusion protocol in an agarose gel model. In the gel phantom models, no significant difference was found in performance parameters between the VT and SF catheter. We report, for the first time, such benchmark characteristics in CED between these two otherwise similar single-end port VT with stylet and end-port non-stylet infusion systems. Results of the current study in agarose gel models suggest that the performance of the VT catheter is comparable to the SF catheter and warrants further investigation as a tool in the armamentarium of CED techniques for eventual clinical use and application.

Eduard Tubina 100. sünniaastapäeva puhul toimus Stockholmis suur mälestuskontsert / Hilma Nerep-Mossin ; fotod: Karin Mickelsson

Index Scriptorium Estoniae

Nerep-Mossin, Hilma

2005-01-01

17. aprillil 2005 Stockholmi Soome Kirikus toimunud kontserdi muusikaarvustus. Esinesid Stockholmi Eesti Segakoor, Projektmeeskoor E. Tubin 100, laulusolistid Katrin Meerits, Liine Carlsson ja Mikko Pulkkinen

"Tallinna kirikurenessanss" valis logo

Index Scriptorium Estoniae

2002-01-01

Katrin Terno logo, millel on kujutatud Aleksander Nevski katedraali, Oleviste ja Tallinna toomkiriku torni siluett, valiti Tallinna kirikute restaureerimise projekti "Tallinna kirikurenessanss" sümboliks

Results of the radiological survey of the Excelsior Steel Ball Company, Tonawanda, New York (TNY005)

International Nuclear Information System (INIS)

McKenzie, S.P.; Brown, K.S.

1998-07-01

At the request of the US Department of Energy (DOE), a team from Oak Ridge National Laboratory conducted two radiological surveys of property belonging to the Excelsior Steel Ball Company, which is surrounded on three sides by the former site of the Linde Uranium Refinery, Tonawanda, New York. The surveys were performed in September 1997 and February 1998. The purpose of the first survey was to determine if radioactive residuals were present from previous activities at the former Linde site. The Linde Air Products Division of Union Carbide Corporation, Tonawanda, New York, had used radioactive materials at that location for work performed under government contract from 1942 through 1948. The purpose of the second survey was to collect additional biased samples from an area of the site where biased sample results showed slightly elevated levels of thorium-232

FIRST OPERATING RESULTS OF A DYNAMIC GAS BEARING TURBINE IN AN INDUSTRIAL HYDROGEN LIQUEFIER

International Nuclear Information System (INIS)

Bischoff, S.; Decker, L.

2010-01-01

Hydrogen has been brought into focus of industry and public since fossil fuels are depleting and costs are increasing dramatically. Beside these issues new high-tech processes in the industry are in need for hydrogen at ultra pure quality. To achieve these requirements and for efficient transportation, hydrogen is liquefied in industrial plants. Linde Gas has commissioned a new 5.5 TPD Hydrogen liquefier in Leuna, Germany, which has been engineered and supplied by Linde Kryotechnik. One of the four expansion turbines installed in the liquefaction process is equipped with dynamic gas bearings. Several design features and operational characteristics of this application will be discussed. The presentation will include results of efficiency and operational reliability that have been determined from performance tests. The advantages of the Linde dynamic gas bearing turbine for future use in hydrogen liquefaction plants will be shown.

Narva osales turismimesil Leningradi oblasti boksis / Tanel Mazur

Index Scriptorium Estoniae

Mazur, Tanel, 1971-

2008-01-01

Ilmunud ka: Narva Postiljon 26. jaan. lk. 1. Narva linnavalitsuse turismispetsialist Katrin Liblik põhjendab, miks osales Narva Helsingis toimunud turismimessil "Matka 2008" Leningradi oblasti boksis

Oskus kuulata / Ellu Maar

Index Scriptorium Estoniae

Maar, Ellu

2007-01-01

Clare Charnley näitus "Keelte and" Hobusepea galeriis kuni 17. XII. Projektis osalevad kaaskunstnikud, Eestist Katrin Kivimaa. Avamisel esitleti raamatut "So communications : translating each other's words"

Plaadid / Liina Valdre, Erik Aru, Tiiu Laks...[jt.

Index Scriptorium Estoniae

2007-01-01

Uutest heliplaatidest Dylan Donkin "Food For Thoughtlessness", Kreatiivmootor "Irratsionaalne", Coco Electrik "Army Behind The Sun", Marc Collin featuring Katrine Ottosen & Valente "Two For The Road", Korn "Untitled"

Poesía y filosofía son de palabra

Directory of Open Access Journals (Sweden)

Santamaría Pargada, Antonio

2006-04-01

Full Text Available The imaginary and sinister concentration-camp chief Otto Friedrich Zur Linde was conceived by Jorge-Luis Borges as an example of misunderstanding philosophy and life, by seeing in them only the power of fight. This conception is compared with a dynamic understanding of philosophy. For Mr. Zur Linde Aristotle and Plato represent this confrontation, and each philosophical debate in history could be considered as a moment in it. But now, in the last fight, the will to power of man has gone beyond all the limits, even of morality. However some modern techniques of appropriation of ancient philosophy are completely opposed to this conception, namely Paul Ricoeur’s theory of fiction and Heidegger’s Sein und Schein,. Ultimately, the close relationship between poetry and philosophy since its origins speak against this thesis. A closer analysis of Nietzsche and Hölderlin will help to enlighten how wrong Zur Linde´s conception is..El siniestro jefe de un campo de concentración Otto Friedrich Zur Linde, concebido por Borges como ejemplo de una interpretación de la filosofía y la vida en la que la lucha es el único motor, es confrontado con una concepción de la filosofía dinámica. Zur Linde mantiene que Aristóteles y Platón son el enfrentamiento filosófico paradigmático. En el último momento del enfrentamiento la voluntad de poder de un nuevo superhombre ha rebasado todos los límites, incluso el de la conciencia. A esto se oponen las técnicas de apropiación filosófica del mundo griego por parte de la modernidad, a saber: el poder de la ficción, el Schein y el Sein así como el nacimiento de la filosofía, tan cercano a la poesía. Bajo este prisma cabe un análisis de Nietzsche y Hölderlin, que reniega de la interpretación de Zur Linde y clarifica que ante todo poetas y filósofos son seres de palabra.

Uhiuus spordimaja annab mitmele klubile kodusaali / Mari-Liis Hüvato

Index Scriptorium Estoniae

Hüvato, Mari-Liis

2006-01-01

Avati Tartu Spordimaja A. Le Coq Sport. Projekteerija Muru & Pere arhitektuuribüroo, sisearhitekt Katrin Kaevats. Kommenteerivad Jaan Veeranna, Janika Mölder, Andres Põhjala, Urmas Tali, Aivo Erkmaa

Radiological Survey Results for the Niagara Mohawk Right-of-Way, Tonawanda, New York (TNY004)

International Nuclear Information System (INIS)

McKenzie, S.P.; Uziel, M.S.

1998-01-01

At the request of the U.S. Department of Energy (DOE), a team from Oak Ridge National Laboratory conducted a radiological survey of a small portion of the Niagara Mohawk Power Corporation right-of-way in Tonawanda, New York. The purpose of the survey was to determine if radioactive residuals had migrated from or been redistributed onto the Niagara Mohawk right-of-way from the former Linde property to the west. The Linde Air Products Division of Union Carbide Corporation, Tonawanda New York, had used radioactive materials at that location for work performed under government contract from 1942 through 1948. The survey was performed in May 1996 in response to Formerly Utilized Sites Remedial Action Program (FUSRAP) requirements. These requirements dictate that the radiological status of certain vicinity properties shall be assessed and documented according to prescribed procedures prior to certification of the property for release for unrestricted use. Such release can only be granted if the property is found to be within current applicable authorized limits. The survey included a gamma scan of accessible areas and the collection and radionuclide analysis of soil samples from the portion of right-of-way located east of the former Linde plant site and north of the railway spur entrance gate. Results of the survey indicate that radioactive material probably originating from the Linde plant is located on the Niagara Mohawk right-of-way in the area surveyed. Surface gamma exposure rates were elevated above typical background levels. Four scattered surface soil samples exceeded DOE guideline values for 238 U, and 8 of 13 surface soil samples exceeded DOE guideline values for 226 Ra. The radionuclide distribution in these samples was similar to that found in materials resulting from former processing activities at the Linde site. It is recommended that the property be designated for remedial action by DOE

Functional characterization of Kv11.1 (hERG) potassium channels split in the voltage-sensing domain.

Science.gov (United States)

de la Peña, Pilar; Domínguez, Pedro; Barros, Francisco

2018-03-23

Voltage-dependent KCNH family potassium channel functionality can be reconstructed using non-covalently linked voltage-sensing domain (VSD) and pore modules (split channels). However, the necessity of a covalent continuity for channel function has not been evaluated at other points within the two functionally independent channel modules. We find here that by cutting Kv11.1 (hERG, KCNH2) channels at the different loops linking the transmembrane spans of the channel core, not only channels split at the S4-S5 linker level, but also those split at the intracellular S2-S3 and the extracellular S3-S4 loops, yield fully functional channel proteins. Our data indicate that albeit less markedly, channels split after residue 482 in the S2-S3 linker resemble the uncoupled gating phenotype of those split at the C-terminal end of the VSD S4 transmembrane segment. Channels split after residues 514 and 518 in the S3-S4 linker show gating characteristics similar to those of the continuous wild-type channel. However, breaking the covalent link at this level strongly accelerates the voltage-dependent accessibility of a membrane impermeable methanethiosulfonate reagent to an engineered cysteine at the N-terminal region of the S4 transmembrane helix. Thus, besides that of the S4-S5 linker, structural integrity of the intracellular S2-S3 linker seems to constitute an important factor for proper transduction of VSD rearrangements to opening and closing the cytoplasmic gate. Furthermore, our data suggest that the short and probably rigid characteristics of the extracellular S3-S4 linker are not an essential component of the Kv11.1 voltage sensing machinery.

Marek Kiisa 9 ametit / Marek Kiisa ; interv. Jaana Liigand

Index Scriptorium Estoniae

Kiisa, Marek

2006-01-01

Kataloogifirma Miss Mary of Sweden juhatuse esimees oma karjäärist, juhtimiskogemustest ning Eesti ja Rootsi organisatsioonimudelitest. Vt. samas: Marek Kiisa; Katrin Verniku lühiintervjuud Marek Kiisaga

Iga tund võib olla riigikaitsetund / Victoria Parmas

Index Scriptorium Estoniae

Parmas, Victoria

2015-01-01

Riigikaitseõpetuse seostamisest teiste õppeainetega. Rocca al Mare koolis teevad riigikaitseõpetuse osas koostööd geograafiaõpetaja Marek Nisuma ning ajalooõpetajad Katrin Martsik ja Ronald Juurmaa

Hillitsetud feministid / Teet Veispak

Index Scriptorium Estoniae

Veispak, Teet, 1955-

2000-01-01

Ajakirja "Ariadne Lõng" esinumbrist, mis esindab liberaalse feminismi vaateid. Katrin Kivimaa artiklist "Teise tootmine - Ida-Euroopa ja feminism". Esile on tõstetud kunstiteadlaste Reet Varblase ja Eda Sepa artiklid.

Journal of Biosciences | Indian Academy of Sciences

Indian Academy of Sciences (India)

2009-02-13

Feb 13, 2009 ... Author Affiliations. Katrin Schaefer1 Fred L Bookstein1 2. Department of Anthropology, University of Vienna, Vienna, Austria; Department of Statistics, University of Washington, Seattle, USA ...

Coaching näitab töötajast hoolimist / Urve Vilk

Index Scriptorium Estoniae

Vilk, Urve

2012-01-01

Konverentsil "Arengukompass 2012: uue ajastu organisatsiooni arendusvahendid" esinenud juhtimiskoolitaja ja sertifitseeritud coach'i Ivar Lukki, Elioni tehnoloogiadirektori Kalev Reiljani ja superviisori Katrin Aava Tallinna Ülikoolist sõnavõttudest

Results of the radiological survey at the Town of Tonawanda Landfill, Tonawanda, New York (TNY001)

International Nuclear Information System (INIS)

Rodriguez, R.E.; Murray, M.E.; Uziel, M.S.

1992-10-01

At the request of the US Department of Energy (DOE), a team from Oak Ridge National Laboratory conducted a radiological survey at the Town of Tonawanda Landfill, Tonawanda, New York. The survey was performed in September 1991. The purpose of the survey was to determine if radioactive materials from work performed under government contract at the Linde Air Products Division of Union Carbide Corporation, Tonawanda, New York, had been deposited in the landfill. The survey included a surface gamma scan and the collection of soil samples for radionuclide analyses. Results of the survey suggest that material originating at the Linde plant may have been deposited in the landfill. Soil samples S54 and B12 contained technologically enhanced levels of 238 U not unlike the product formerly produced by the Linde plant. In contrast, samples B4A, B5A and B7B, containing elevated concentrations of 226 Ra and 230 Th with much lower concentrations of 238 U, were similar to the residue or byproduct of the refinery operation conducted at the Linde plant. In 24 instances, soil samples from the Town of Tonawanda Landfill exceeded DOE guideline values for 238 U, 226 Ra, and/or 230 Th in surface or subsurface soil. Nine of these samples contained radionuclide concentrations more than 30 times the guideline value

Tartu vaimukas tants / Kertu Käämbre

Index Scriptorium Estoniae

Käämbre, Kertu

2007-01-01

"Uue tantsu" festivalist Tartus. Tantsuetendustest: Katrin Essensoni "Manusega mõtted", Renate Valme "Mesta", Mart Kangro "Start. Based on a True Story", Kaja Kannu "There are Laika Dogs Living in Estonia"

HP fotovõistluse finalistid veebis / Henrik Roonemaa

Index Scriptorium Estoniae

Roonemaa, Henrik

2002-01-01

Hewlett-Packardi koduleheküljel on üleval rahvusvahelise digitaalfotograafia konkursi HP Invision Digital Photography Awards 2002 finalistide tööd, nende hulgas Katrin Arraku foto "Minu kala Vallo"

PÖFF-i festivalid pakuvad aina paremat programmi / Margit Rebane

Index Scriptorium Estoniae

Rebane, Margit

2004-01-01

VIII Pimedate Ööde filmifestivali alafestivalid : tudengifilmifestival Sleepwalkers, laste- ja noortefilmide festival Just Film, animafilmifestival Animated Dreams (korraldajad Katrin Rajasaare, Elen Lotman, Heilika Võsu). Lisa : Kus toimub? Palju maksab?

Sisustusgiidi uudised / Mari Masso

Index Scriptorium Estoniae

Masso, Mari

2007-01-01

Standardi uuest kapiseeriast (disainer Katrin Soans) ja koostööst Jaapani toolitootja Okamuraga; helisummutavatest seinapaneelidest; Verner Pantoni toolist lastele; Alberto Meda pöörlevast töötoolist

Setting research priorities to improve the health of children and young people with neurodisability: a British Academy of Childhood Disability-James Lind Alliance Research Priority Setting Partnership.

Science.gov (United States)

Morris, Christopher; Simkiss, Doug; Busk, Mary; Morris, Maureen; Allard, Amanda; Denness, Jacob; Janssens, Astrid; Stimson, Anna; Coghill, Joanna; Robinson, Kelly; Fenton, Mark; Cowan, Katherine

2015-01-28

To engage young people, parent carers and clinicians in a systematic process to identify and prioritise research questions regarding ways to improve the health and well-being of children and young people with neurodisability. British Academy of Childhood Disability (BACD)-James Lind Alliance research priority setting partnership bringing together patients, carers and clinicians as equal stakeholders. UK health service and community. The BACD Strategic Research Group formed the partnership. A Steering Group was established; charity and professional partner organisations were recruited. Suggestions were gathered in an open survey and from research recommendations for statutory guidance. Items were aggregated to formulate indicative research questions and verified as uncertainties from research evidence. An interim survey was used to rank the questions to shortlist topics. A mixed group of stakeholders discussed the top 25 questions at the final priority setting workshop agreeing a final rank order and the top 10 research priorities. Partner organisations were 13 charities and 8 professional societies. 369 people submitted suggestions (40% non-clinicians). 76 people participated in the interim prioritisation (26 parents, 1 young person, 10 charity representatives, 39 clinicians); 22 took part in the final workshop (3 young people, 7 parents, 3 charity representatives, 9 professionals). The top three research priorities related to (1) establishing the optimal frequency and intensity (dose) for mainstream therapies, (2) means for selecting and encouraging use of communication strategies and (3) ways to improve children's attitudes towards disability. The top 10 included evaluating interventions to promote mobility, self-efficacy, mental health, continence, physical fitness, educational inclusion and reduce impacts of sleep disturbance. The methodology provided a systematic and transparent process to identify research priorities that included stakeholders that have

Results of the radiological survey at Two Mile Creek, Tonawanda, New York (TNY002)

International Nuclear Information System (INIS)

Murray, M.E.; Rodriguez, R.E.; Uziel, M.S.

1997-08-01

At the request of the US Department of Energy (DOE), a team from Oak Ridge National Laboratory conducted a radiological survey at Two Mile Creek, Tonawanda, New York. The survey was performed in November 1991 and May 1996. The purpose of the survey was to determine if radioactive materials from work performed under government contract at the Linde Air Products Division of Union Carbide Corporation, Tonawanda, New York, had been transported into the creek. The survey included a surface gamma scan in accessible areas near the creek and the collection of soil, sediment, and core samples for radionuclide analyses. Survey results indicate that no significant material originating at the Linde plant is presently in the creek. Three of the 1991 soil sample locations on the creek bank and one near the lake contained slightly elevated concentrations of 238 U with radionuclide distributions similar to that found in materials resulting from former processing activities at the Linde site

Fragmente taevase laega labürindist / Jan Kaus

Index Scriptorium Estoniae

Kaus, Jan, 1971-

2007-01-01

Arvustus: Benjamin, Walter. Ühesuunaline tänav : [väikesed proosalood] / saksa keelest tõlkinud [ja järelsõna:] Katrin Kaugver. Tallinn : Kultuurileht, 2007. (Loomingu Raamatukogu ; 2007, 25-26)

Mitte ainult spordihoone = More than a Gym / Tuuli Köller

Index Scriptorium Estoniae

Köller, Tuuli

2009-01-01

Tartus 2009. a. valminud Eesti Maaülikooli spordihoonest, mille arhitektid on Maarja Kask, Karli Luik ja Ralf Lõoke, projekteerija AB Salto, sisekujundajad Katrin Kaevats ja Jaan Frank Port. Projekt 2007

Tallinna Ülikooli kirjastus tegi uue raamatusarja

Index Scriptorium Estoniae

2013-01-01

Tallinna Ülikooli kirjastus hakkas välja andma uut raamatusarja "Acta Universitatis Tallinnensis. Artes", mille avaraamatuks on Katrin Kivimaa koostatud artiklikogumik "Working with Feminism: Curating and Exhibitions in Eastern Europe"

Ökokontor on õhu- ja loomingurikas / Nelli Pello

Index Scriptorium Estoniae

Pello, Nelli

2007-01-01

Tööruumide säästvast renoveerimisest looduslike materjalidega. Tartu trükikojast Triip, reklaamiagentuuri Dreamers kontorist, Säästva Arengu Klubi büroost. Kommenteerivad Eva Peedimaa, Katrin Kull

Venezia filmifestivali punane vaip ootab tänavu ka eestlasi / Tiit Tuumalu

Index Scriptorium Estoniae

Tuumalu, Tiit, 1971-

2007-01-01

Eesti mängufilm "Sügisball" (režissöör Veiko Õunpuu, produtsent Katrin Kissa) esilinastub 7. septembril Venezia 64. filmifestivali konkursiprogrammis Orizzonti. Ka teistest võistlevatest filmidest

Rahvuslikus stiilis lastetuba meeldis nii asjatundjatele kui ka publikule / Siret Mägi

Index Scriptorium Estoniae

Mägi, Siret

2007-01-01

Tallinna Mustika ostukeskuses kuulutati välja sisekujunduskonkursi "Rahvuslik tuba" võitjad. Parimaks tunnistati Eva Herrera, II koha pälvis Gudrun Vung ning III koha Helen Sarapuu ja Katrin Rooger

"Ja govorju : iskusstvo!" / Anastasia Semjonova

Index Scriptorium Estoniae

Semjonova, Anastasia

2006-01-01

Tartu kunstikuu 2006 avamisest ja üritustest. Peakorraldajaks on Tartu Kõrgem Kunstikool, üldjuht Katrin Ruus. Kunstikuu staabiks on Tartu vana kaubamaja. Raeplatsil avati Kirke Kangro valmistatud jääskulptuur

V zashtshitu zdanija narvskoi Birzhi / Jüri Kuuskemaa

Index Scriptorium Estoniae

Kuuskemaa, Jüri, 1942-

2006-01-01

Eesti Muinsuskaitse Seltsi juhatuse avaldus seoses Tartu Ülikooli Narva kolledzhi projektiga. Sisaldab retsensiooni projektile "Vihm" (autorid Katrin Koov, Indrek Peil, Siiri Vallner), mis on inspireeritud inglise skulptori Rachel Whitereadi loomingust

Tallinnasse Rävala pst. 19 kavandatava Tallinna Muusikakeskkooli, Tallinna Balletikooli ning G. Otsa nimelise muusikakooli ühise õppehoone arhitektuurikonkurss = Architectural Competition for the Joint School Building of Tallinn Music-Specialised

Index Scriptorium Estoniae

Puusepp, Raivo

2003-01-01

I preemia - Andres Siim, Krister Ausing, II - Marika Lõoke, III - Maia Tüür, Andres Sevtshuk, Gabriel Evangelisti, ostupreemiad: Armin Valter, Vilen Künnapu ning Siiri Vallner, Katrin Koov, Veronika Valk

Under ja tema (kirja)-mehed / Mati Soomre

Index Scriptorium Estoniae

Soomre, Mati, 1944-2015

2006-01-01

20. nov. Kumu auditooriumis esietendunud Ühenduse R.A.A.A.M teatriprojekt "Under" poetess Marie Underist. Lavastajad Merle Karusoo ja Raimo Pass, kunstnik Jaagup Roomet, helilooja Urmas Lattikas, peaosas Katrin Saukas

Underist, Underiga, Underini Underina, Underiks Underita / Katre Väli

Index Scriptorium Estoniae

Väli, Katre

2006-01-01

20. nov. Kumu auditooriumis esietendunud Ühenduse R.A.A.A.M teatriprojekt "Under" poetess Marie Underist. Lavastajad Merle Karusoo ja Raimo Pass, kunstnik Jaagup Roomet, helilooja Urmas Lattikas, peaosas Katrin Saukas

Eesti mood esitles end Stockholmis / Peep Sooman

Index Scriptorium Estoniae

Sooman, Peep, 1978-

1999-01-01

Eesti moepäevadel Stockholmis esitleti moeshow'l üle 80 rõivakollektsiooni, osalesid: Baltika, Klementi, Sangar, Zik-Zak (Ivo Nikkolo), Katrin Kuldma Moemaja, Arne Studio, Hipo, Uljas & Tütred, Virulane, Althea.

Karzai pääses raketirünnakust eluga / Hendrik Vosman

Index Scriptorium Estoniae

Vosman, Hendrik

2008-01-01

Afganistani pealinnas Kabulis toimunud sõjaväeparaadile Talibani korraldatud raketirünnakus hukkus kolm inimest, president Hamid Karzai pääses vigastusteta. Kabulis viibinud Euroopa Parlamendi saadiku Katrin Saksa arvamus

Kliiniline kapitalism ja naise neim / Vaapo Vaher

Index Scriptorium Estoniae

Vaher, Vaapo, 1945-

2011-01-01

Tutvustus: Kõiv, Salme. Reet Tammiku. Tallinn : Eesti Raamat, 2011 ; Kalda, Katrin. Eesti romaan / tõlkinud Anti Saar. Tallinn : Varrak, 2011 ; Zola, Émile. Saak / tõlkinud Kaja Riesen. Tallinn : Eesti Raamat, 2011

Saukas ja Karusoo tõid Marie Underi elu teatrilavale / Andres Laasik

Index Scriptorium Estoniae

Laasik, Andres, 1960-2016

2006-01-01

20. nov. Kumu auditooriumis esietendunud Ühenduse R.A.A.A.M teatriprojekt "Under" poetess Marie Underist. Lavastajad Merle Karusoo ja Raimo Pass, kunstnik Jaagup Roomet, helilooja Urmas Lattikas, peaosas Katrin Saukas

Eduard Odinets : "Olen eestlane, kelle emakeel on vene keel" / Eduard Odinets ; interv. Erik Kalda

Index Scriptorium Estoniae

Odinets, Eduard, 1976-

2006-01-01

Ilmunud ka: Severnoje Poberezhje Ilmunud ka: Severnoje Poberezhje : Subbota 3. juuni lk. 3. Riigikogu sotsiaaldemokraatide fraktsiooni nõunik oma poliitikukarjäärist. Arvamust avaldab Katrin Saks ja Meelis Goldberg (Severnoje Pob.)

Plaadid / Kaarel Kressa

Index Scriptorium Estoniae

Kressa, Kaarel, 1983-

2007-01-01

Uutest heliplaatidest Kasabian "Empire", Katrin Mandel ja Lauri Saatpalu "Ei kunagi", The Hold Steady "Boys & Girls in America", "Corinne Bailey Rae", FAll Out Boy "Infinity On High", Laleh "Prinsessor", Melody Club "Scream"

Technologies of 1.8 K / 2.4 kW helium refrigerators and cold compressors for LHC

International Nuclear Information System (INIS)

Saji, Nobuyoshi; Yoshinaga, Seiichirou; Asakura, Hiroshi; Shimba, Toru; Honda, Tadaaki; Mori, Mikio

2005-01-01

For the LHC (Large Hadron Collider) project of the CERN (Conseil Europeen pour la Recherche Nucleaire), the Swiss-Japanese consortium IHI/Linde Kryotechnik AG delivered a 1.8 K helium refrigeration system. Linde has produced many helium refrigeration systems and IHI has designed and manufactured cold compressors that utilize many advanced technologies and innovative ideas for turbo machinery. The compressor has the characteristics of the highest efficiency in the world. This paper describes the 1.8 K helium refrigeration system and performance test results at CERN. (author)

Miks peab lõhkuma hägustunud piire? / Reelika Reinomägi

Index Scriptorium Estoniae

Reinomägi, Reelika

2007-01-01

Kaasaegse tantsulavastuse ja teatri ühisosast, seoses festivaliga "Uus tants". Tantsuetendustest: Katrin Essensoni "Manusega mõtted", Mart Kangro "Start. Based on a True Story", Kaja Kannu "There are Laika Dogs Living in Estonia"

Unetuma ülemlaul / Arne Merilai

Index Scriptorium Estoniae

Merilai, Arne, 1961-

2011-01-01

20. nov. 2006 Kumu auditooriumis esietendunud Ühenduse R.A.A.A.M teatriprojekt "Under" poetess Marie Underist. Lavastajad Merle Karusoo ja Raimo Pass, kunstnik Jaagup Roomet, helilooja Urmas Lattikas, peaosas Katrin Saukas

Kunstiteaduslik doktoritöö EKA-s kaitstud / Ingrid Ruudi

Index Scriptorium Estoniae

Ruudi, Ingrid

2005-01-01

Heie Treier "Kohalik modernsus kunstis. Eesti varamodernistliku kunsti teoreetiline ja ajalooline kontseptualiseerimine ning Karl Pärsimägi paradigmaleidmise perioodil". Juhendaja Thomas McEvilley, eelretsensent Katrin Kivimaa ja Ene Lamp. Oponent Jaak Kangilaski

Kes vajab pooltõdedele rajatud patriotismi / Valle-Sten Maiste

Index Scriptorium Estoniae

Maiste, Valle-Sten, 1972-

2007-01-01

Kuressaare Linnateatri ja ühenduse R.A.A.A.M koostöös valminud dokumentaalmaterjalidel põhinevast lavastusest Betti Alverist ja Heiti Talvikust "Võlg". Loo autor on Katrin Saukas, lavastaja Merle Karusoo

Hotelli Palace**** renoveerimine = Renovation of the hotel Palace**** / Argo Vaikla

Index Scriptorium Estoniae

Vaikla, Argo, 1966-

2015-01-01

Hotell Palace Tallinnas Vabaduse väljak 3, valminud 2014. Hoone rekonstrueerimisprojekt Reet Valk (AB Reet Valk), sisearhitektid Katrin Vaikla, Argo Vaikla, Mari-Liis Süld, Riin Luuk. 2014. aasta Kultuurkapitali Arhitektuuripreemia kandidaat

Under Under Under / Merit Kask

Index Scriptorium Estoniae

Kask, Merit

2006-01-01

20. nov. esietendub Kumu auditooriumis MTÜ Ühenduse R.A.A.A.M teatriprojekt "Under" poetess Marie Underist. Lavastajad Merle Karusoo ja Raimo Pass, kunstnik Jaagup Roomet, helilooja Urmas Lattikas, peaosas Katrin Saukas

NU Performance'il läheb kunst bändiks kätte ära / Janar Ala

Index Scriptorium Estoniae

Ala, Janar, 1979-

2009-01-01

III Nu Performance festival "Recycle Pop" Tallinnas Kanuti Gildi saalis 11.11.-14.11.2009, kuraator Anders Härm. Osalevad teatrigrupp Baktruppen Norrast, Carole Douillard Prantsusmaalt, Lotte Jürjendal ja Katrin Ratte Eestist

Kirev moepilt / Britt Rosen

Index Scriptorium Estoniae

Rosen, Britt, 1968-

2007-01-01

FIBITi moepäevadest Tallinnas Viru keskuses, stilistid Gerli Tinn, Liisi Eesmaa, Kirill Safonov. Kuldnõela auhinna pälvis Katrin Kuldma kollektsiooni Chocolat eest. Oma loomingut esitlesid Reet Aus, Tiiu Roosma, Marika Siska

14. VII avati Rael Arteli galerii fotoruumis...

Index Scriptorium Estoniae

2004-01-01

Anu Allase kureeritud näitus "Juhitud reisid/Guided Tours". Näitusel osalevad Liisi Peets, Katrin Tees, Piret Räni, Anu Vahtra, Daisy Lappard, Tiit Sokk (Ulvi Tiit & Marili Sokk), Raivo Hool ja Rataplan

Semester piiri taga, ookeanil loksuvas laevaauditooriumis / Agne Narusk

Index Scriptorium Estoniae

Narusk, Agne

2008-01-01

Ülikoolist laevas, The Scholar Ship programmist, mis viib eri rahvusest üliõpilased neljaks kuuks ümbermaailma-õppereisile. Oma kogemusi laevas õppimisest jagavad Katrin Kaun, Natalja Tamm ja Hanna-Liina Linnasmäe

Popmuusika / Valner Valme

Index Scriptorium Estoniae

Valme, Valner, 1970-

2007-01-01

Uutest heliplaatidest The Charlatans "Forever", Young Jeezy "The Inspiration", Girls Aloud "The Sound Of Girls Aloud", Six Organs Of Admittance "The Sun Awakens", Take That "Beautiful World", Lauri Saatpalu & Katrin Mandel "Ei kunagi", "Republicafrobeat"

Põrandate pillerkaar / Ingrid Sembach-Hõbemägi

Index Scriptorium Estoniae

Sembach-Hõbemägi, Ingrid

2008-01-01

Soovitusi põrandakatete valikuks. Materjalide (puit, kork, linoleum, laminaat, plaadid, kivid, vaipkate) plussid ja miinused. Kommenteerivad Katrin Kuningas-Leius salongist Ruutmeeter, Küllike Uus Interno Plaadimajast, Anu Jaanson Vivarecist, Siret Antsmäe Floorinist

International conference "Cultural Plurality in Estonia : Policies and Solutions"

Index Scriptorium Estoniae

2000-01-01

Ettekandjad: Katrin Saks, Mall Hellam, Mati Luik, Kirsti Häkkinen, Vello Pettai, Ivi Proos, Katri Raik, NiinaOrhimenko, Ib Ostergaard Rasmussen, Urve Läänemets, Jüri Valge, Aleksander Dusman, Raivo Juurak, Rein Ruutsoo

Must maja, valge aed / Mihkel Karu

Index Scriptorium Estoniae

Karu, Mihkel, 1983-

2012-01-01

Laagris 2010. aastal valminud eramust. Tänavapoolne aed on valatud betoonist. Arhitektid: Peeter Pere, Urmas Muru, Anna-Maria Erik (AB Muru & Pere). Sisearhitektid: Katrin Kaevats, Peeter Pere, Urmas Muru. Projekt. 2008. Peeter Pere kommentaar

Sõlmes alumiiniummaja = Aluminium House in a Knot

Index Scriptorium Estoniae

2008-01-01

Alumiiniumplaatidega kaetud sõlmekujulise plaaniga eramu (256 m2). Arhitektid: Peeter Pere, Urmas Muru. Projektbüroo: Muru & Pere. Konsultant Katrin Kaevats. Valmis: 2007. 2 plaani, 4 värv. välisvaadet, sisevaade

Att utforma en teknisk manual : Med tillhörande riktlinjer

OpenAIRE

Runvall, Linda; Parantainen, Satu

2007-01-01

Vi, Linda Runvall och Satu Parantainen, har gjort vårt examensarbete för företaget Leine & Linde i Strängnäs. De tillverkar pulsgivare som används inom industrin. Examensarbetet bestod av att göra om en befintlig manual och skriva guidelines (riktlinjer) till Leine & Lindes personal. Under vårt examensarbete har vi använt oss av våra kunskaper inom informationsdesign. Rune Pettersson, professor i informationsdesign vid Mälardalens högskola, beskriver ämnet informationsdesign såhär: ”I...

Baltic notes : the best in music

Index Scriptorium Estoniae

2005-01-01

Heliplaatidest: "World Lullabies", Mielavs un Parcelaji "Paruna ar sevi", InCulto "Post Sov Pop", Lauri Saatpalu & Katrin Mandel "Sa Oled Hea", D.J.Critikal "Chapter One Ehk Teine Maitse", Jurga "Aukso Pieva", Terminaator "Go Live"

"Ruudi" võitis Tokio festivali peaauhinna

Index Scriptorium Estoniae

2006-01-01

Lastefilm "Ruudi" sai Tokyo 14. lastefilmide festivalil Kodomotachino parima mängufilmi auhinna. Filmi režissöör Katrin Laur ja nimiosas esinenud 8-aastane Paul Oskar Soe olid ka festivalikülalised

Eesti Maaülikooli spordihoone = The Sports Hall of the Estonian University of Life Sciences / Margit Mutso

Index Scriptorium Estoniae

Mutso, Margit, 1966-

2010-01-01

Tartus Kreutzwaldi 3 asuva EMÜ spordihoone arhitektuursest lahendusest. Arhitektid: Maarja Kask, Karli Luik, Ralf Lõoke (Salto AB). Sisearhitektid: Katrin Kaevats, Jaan Port (Funk AB). Žürii liikme Kalle Komissarovi hinnang kultuurkapitali aastapreemiale esitatud hoonele

Feministid põõsas / Olev Remsu

Index Scriptorium Estoniae

Remsu, Olev, 1947-

1996-01-01

Feminismist seoses ameerika filmiga 'Striptiis' ("Striptease", re̓issöör Andrew Bergman, USA 1996). Vastukaja: Kivimaa, Katrin. Feminist tuleb põõsast välja // Eesti Päevaleht. - 1996. - 4. dets. - Lk. 7

Azimuthal Structure of the Sand Erg that Encircles the North Polar Water-Ice Cap

Science.gov (United States)

Teodoro, L. A.; Elphic, R. C.; Eke, V. R.; Feldman, W. C.; Maurice, S.; Pathare, A.

2011-12-01

The sand erg that completely encircles the perennial water-ice cap that covers the Martian north geographic pole displays considerable azimuthal structure as seen in visible and near-IR images. Much of this structure is associated with the terminations of the many steep troughs that cut spiral the approximately 3 km thick polar ice cap. Other contributions come from the katabatic winds that spill over steep-sided edges of the cap, such as what bounds the largest set of dunes that comprise Olympia Undae. During the spring and summer months when these winds initiate from the higher altitudes that contain sublimating CO2 ice, which is very cold and dry, heat adiabatically when they compress as they lose altitude. These winds should then remove H2O moisture from the uppermost layer of the sand dunes that are directly in their path. Two likely locations where this desiccation may occur preferentially is at the termination of Chasma Boreale and the ice cap at Olympia Undae. We will search for this effect by sharpening the spatial structure of the epithermal neutron counting rates measured at northern high latitudes using the Mars Odyssey Neutron Spectrometer (MONS). The epithermal range of neutron energies is nearly uniquely sensitive to the hydrogen content of surface soils, which should likely be in the form of H2O/OH molecules/radicals. We therefore convert epithermal counting rates in terms of Water-Equivalent-Hydrogen, WEH. However, MONS counting-rate data have a FWHM of ~550 km., which is sufficiently broad to prevent a close association of WEH variability with images of geological features. In this study, we reduce spurious features in the instrument smeared neutron counting rates through deconvolution. We choose the PIXON numerical deconvolution technique for this purpose. This technique uses a statistical approach (Pina 2001, Eke 2001), which is capable of removing spurious features in the data in the presence of noise. We have previously carried out a detailed

The magnetic field investigation on the ARASE (ERG) mission: Data characteristics and initial scientific results

Science.gov (United States)

Matsuoka, A.; Teramoto, M.; Nomura, R.; Nose, M.; Fujimoto, A.; Tanaka, Y.; Shinohara, M.; Nagatsuma, T.; Shiokawa, K.; Obana, Y.; Miyoshi, Y.; Takashima, T.; Shinohara, I.

2017-12-01

The ARASE (ERG) satellite was successfully launched on December 20 2016. A fluxgate magnetometer (MGF) was built for the ARASE satellite to measure DC and low-frequency magnetic field. The requirements to the magnetic field measurements by ARASE was defined as (1) accuracy of the absolute field intensity is within 5 nT (2) angular accuracy of the field direction is within 1 degree (3) measurement frequency range is from DC to 60Hz or wider. MGF measures the vector magnetic field with the original sampling frequency of 256 Hz. The dynamic range is switched between +/-8000nT and +/- 60000nT according to the background field intensity. The MGF initial checkout was carried on January 10th 2017, when the MGF normal performance and downlinked data were confirmed. The 5-m length MAST for the sensor was deployed on 17th January. The nominal operation of MGF started in March 2017. The MGF data are calibrated based on the results from the ground experiments and in-orbit data analysis. The MGF CDF files are distributed by the ARASE Science Center and available by Space Physics Environment Data Analysis Software (SPEDAS). The acceleration process of the charged particles in the inner magnetosphere is considered to be closely related to the deformation and perturbation of the magnetic field. Accurate measurement of the magnetic field is required to understand the acceleration mechanism of the charged particles, which is one of the major scientific objectives of the ARASE mission. We designed a fluxgate magnetometer which is optimized to investigate following topics; (1) accurate measurement of the background magnetic field - the deformation of the magnetic field and its relationship with the particle acceleration. (2) MHD waves - measurement of the ULF electromagnetic waves of frequencies about 1mHz (Pc4-5), and investigation of the radiation-belt electrons radially diffused by the resonance with the ULF waves. (3) EMIC waves - measurement of the electromagnetic ion

Genre and Everyday Conversation

DEFF Research Database (Denmark)

Gregersen, Frans

2015-01-01

The paper outlines the analysis of speech genres synchronically and diachronically and exemplifies how speech genres are emulated and transformed in an analysis of a piece of literary fiction by the Danish author Katrine Marie Guldager...

Disainikaart : Island / Eve Arpo

Index Scriptorium Estoniae

Arpo, Eve

2009-01-01

Islandi disaineritest, disainifirmadest, arhitektidest. Katrin Olina, Margrét Hardardóttir ja Steve Christer (Studio Granda), Guđjón Samúelsson (1887-1950), Ingibjörg Hanna Bjarnadottir, Hrafnkell Birgisson, Studio Bility jt.

Tasku kaubandus- ja vabaajakeskuse üldruumid ja konverentsikeskus = Tasku shopping and recreational centre common areas and conference centre / Margit Mutso

Index Scriptorium Estoniae

Mutso, Margit, 1966-

2009-01-01

Tartus Turu 2 asuvas Tasku keskuses asuvad ruumid kujundasid Argo Vaikla ja Katrin Vaikla (Vaikla Disain). Hoone arhitektid on Madis Renter ja Kristiina Renter (AB Kalle Rõõmus). Žürii hinnang kultuurkapitali aastapreemiale esitatud sisekujundusele

"Ruudi" - helge muinasjutt lastele, iroonia vanematele / Teelemari Loonet

Index Scriptorium Estoniae

Loonet, Teelemari, 1987-

2006-01-01

Lastefilm "Ruudi" : stsenaristid Aare Toikka, Aarne Mägi : režissöör Katrin Laur : nimiosas lapsnäitleja Paul Oskar Soe : operaator Rein Kotov : Allfilm - MRP Matila Röhr Productions - Schmidtz Katze Filmkollektiv 2006

Kaadris: "Naerata ometi" / Ulve Määrits

Index Scriptorium Estoniae

Määrits, Ulve

2012-01-01

Restaureeriti mängufilm "Naerata ometi". Sel puhul toimus ringreis Tilsis ning taastatud filmi esitlus Põlva kultuurikeskuses, kus osalesid ning meenutasid filmi valmimist ka lavastaja Arvo Iho ning osatäitjad Katrin Tamleht ja Kerttu Aaving

Pärnu Kontserdimaja arhitektuurikonkurss = Architectural Competition of Pärnu Concert Hall / Martti Preem

Index Scriptorium Estoniae

Preem, Martti, 1949-

2001-01-01

Asukohavalikust, premeeritud ja äramärgitud töödest. Konkursi tulemused: I preemia - Hanno Grossschmidt, Katrin Koov, Kaire Nõmm, Üla Koppel; II - Indrek Erm, Emil Urbel; III - Kalle Komissarov, Andres Ojari. 21 ill.

Kuidas saada hakkama õpilaskoduta? / Ülle Luisk, Toomas Mitt, Aivar Part ... [jt.

Index Scriptorium Estoniae

2011-01-01

Küsimusele vastasid: Viljandi gümnaasiumi direktor Ülle Luisk, Tõstamaa keskkooli direktor Toomas Mitt, Rakvere gümnaasiumi direktor Aivar Part, Tartu kutsehariduskeskuse direktor Andrus Kompus, Võru Kreutzwaldi gümnaasiumi direktor Katrin Martinfeld

Living with a parasite / Elo-Hanna Seljamaa

Index Scriptorium Estoniae

Seljamaa, Elo-Hanna, 1980-

2004-01-01

Ehtekunstnike Kärt Marani (s. 1980), Argo Männiku (s. 1977), Bruno Lillemetsa (s. 1979), Sven Tali, Ester Faimani (s. 1975), Maarja Niinemäe ja Katrin Veegeni näitus "Tallinna lennuväli : anti-venenos"

Plaadid / Priit Hõbemägi

Index Scriptorium Estoniae

Hõbemägi, Priit, 1957-

2005-01-01

Uutest heliplaatidest Neil Young "Prairie Wind", Sigur Ros "Takk...", Paul McCartney "Chaos and Creation in the Backyard", Lauri Saatpalu, Katrin Mandel "Sa oled hea", "Rock2005", The Corrs "Home", Dandy Warhols "Odditorium or Warlords of Mars"

64. Venezia filmifestivalil kuuleb palju inglise keelt / Andris Feldmanis

Index Scriptorium Estoniae

Feldmanis, Andris, 1982-

2007-01-01

Eesti mängufilm, Mati Undi romaani "Sügisballi" ekraniseering (režissöör Veiko Õunpuu, produtsent Katrin Kissa) valiti esimese Eesti filmina homme algava Venezia 64. filmifestivali konkursiprogrammi Orizzonti. Festivali võistluskava filmidest

Teavikute ost riigihankega / Meeli Veskus

Index Scriptorium Estoniae

Veskus, Meeli, 1953-

2007-01-01

1. maist 2007 hakkas kehtima uus riigihangete seadus, mida raamatukogudes tuleb järgida teavikuid komplekteerides. Lisa: "Raamatukogu" küsib: kuidas riigihangete seadust rakendatakse? Vastavad Tallinna Keskraamatukogu direktor Kaie Holm ja Rapla Keskraamatukogu pearaamatukoguhoidja Katrin Niklus

Festivalipäevik III / Margaret Tali, Anu Allas, Margit Tõnson...[jt.

Index Scriptorium Estoniae

2005-01-01

Rahvusvaheline NU Performance festival "Continental Breakfast" Tallinnas Kanuti Gildi saalis 2.-24. nov. 2005. Hollandlase Kim H. Veltmani loengu formaadis performance "World tree". Katrin Essensoni performance "Designed to make difference". Gob Squad (Saksamaa/Inglismaa) "Super Night Shot".

Substâncias ergásticas foliares de espécies amazônicas de Oenocarpus Mart. (Arecaceae: caracterização histoquímica e ultra-estrutural Leaf ergastic substances of Amazonian species of Oenocarpus Mart. (Arecaceae: histochemical and ultrastructural characterization

Directory of Open Access Journals (Sweden)

Rolf Junior Ferreira Silva

2009-01-01

Full Text Available O presente estudo teve por objetivo diagnosticar e caracterizar as substâncias ergásticas foliares de Oenocarpus bacaba Mart., O. distichus Mart., O. mapora H. Karst. e O. minor Mart. através de microscopias óptica e eletrônica de varredura, análises histoquímicas e microanálises físicas. Secções transversais e longitudinais, assim como maceração foram realizadas em material botânico fixado. As análises histoquímicas foram empregadas em material botânico in natura, seguindo-se protocolos específicos para mucilagem, amido e sílica. Microanálises físicas foram feitas com Energy Dispersive Spectroscopy (EDS detector. Nas espécies estudadas de Oenocarpus Mart., as substâncias ergásticas foliares correspondem a mucilagem amorfa; grãos de amido poliédricos do tipo simples e sílica opalina sob a forma de corpos elípticos e esféricos-globosos de superfície espiculada, ambos com elevado teor de dióxido de silício. As observações microscópicas, os testes histoquímicos e as microanálises físicas permitiram diagnosticar, caracterizar e elucidar a estrutura e ultra-estrutura das substâncias ergásticas ocorrentes nas folhas dos táxons analisados de Oenocarpus Mart.The purpose of this study was to diagnose and characterize the leaf ergastic substance of Oenocarpus bacaba Mart., O. distichus Mart., O. mapora H. Karst. and O. minor Mart. by light and scanning electron microscopy, histochemical analyses and physical microanalyses. Transverse and longitudinal sections as well as maceration were made in fixed botanical material. The histochemical analyses were made in non-fixed botanical material, using specific tests for mucilage, starch and silica. An Energy Dispersive Spectroscopy (EDS detector was used for the physical microanalyses. In the Oenocarpus Mart. species studied, the leaf ergastic substances corresponded to amorphous mucilage, simple-type polyhedrical starch grain and opaline silica in the shape of elliptical

Pop / Lauri Tikerpe

Index Scriptorium Estoniae

Tikerpe, Lauri

2008-01-01

Heliplaatidest: Pastacas "Snatsit Some Si-Si", Metro Luminal "Sassis", Nitrous "Outlaw Racer", The Sun "Unisex", Laur ja Sadam "Kirjad maale", Pilvikud "Päikesepatarei", Katrin Mandel "Peegeldus", Kukerpillid & Metsatöll "Suured koerad, väiksed koerad", Ultramelanhool "Materjal"

Briti hotell Dunkri tänavas / Piret Tali

Index Scriptorium Estoniae

Tali, Piret, 1972-

2005-01-01

Liisi Murula ja Raili Nõlvaku kujundatud hotell Merchants House, restoran KN Cayenne, baar Ice Bar ja kohvik Cafe Time Tallinnas. Kasutatud ka tekstiilikunstnik Ülle Raadiku ja klaasikunstnik Rait Partsi töid. Valgustite autor ehtekunstnik Katrin Sipelgas

"Ekspeditsioon Wunderlich" = "Expedition Wunderlich" / Carl-Dag Lige, Hannes Praks ; kommenteerinud Triin Ojari

Index Scriptorium Estoniae

Lige, Carl-Dag, 1982-

2016-01-01

Näitus "Ekspeditsioon Wunderlich" Eesti Arhitektuurimuuseumis. Autorid Katrin Talvik, Merilin Tee, Sabine Suuster, Martin Saar, Karl Taul, Alden Jõgisuu, Tõnu Lensment, Aadam Kaarma, Cael-Dag Lige, Hannes Praks. Näitus on Eesti Kunstiakadeemia ja Eesti Arhitektuurimuuseumi ühisprojekt

"Continental Breakfast" Tallinnas / Anders Härm

Index Scriptorium Estoniae

Härm, Anders, 1977-

2005-01-01

2.-24. XI Nu Performance Festival Kanuti gildi saalis ja Tallinna Kunstihoones. Osalejatest. Eestit esindab Katrin Essenson. Kunstihoones toimub satelliitüritusena näitus "Elavad skulptuurid", Linnagaleriis Liina Siibi näitus briti kirjanikust Christopher Marlowe'st

Uue mängufilmi võtted / E. K.

Index Scriptorium Estoniae

E. K.

2008-01-01

Allfilm koos Saksa, Soome ja Iiri partneritega alustas Tallinnas action-mängufilmi "Kid & Killer" võtteid (režissöör Hannu Salonen, stsenaristid Mart Kivastik ja Katrin Laur, operaator Rein Kotov, produtsent Piret Tibbo-Hudgins)

Staariteatri anatoomia performance'i-kunsti vormis / Janar Ala

Index Scriptorium Estoniae

Ala, Janar, 1979-

2009-01-01

Nu Performance festival III "Recycle Pop" 11.11.-14.11. 2009 Kanuti Gildi saalis Tallinnas. Norra teatritrupi Bäktruppen, prantsuse kunstniku Carole Douillard'i, Lotte Jürjendali ja Katrin Ratte, Maria Arusoo ja Maria Juure, Erki Luuki etteastetest

Ainult 1%-meestest ei ole erektsioonihäire ravitav

Index Scriptorium Estoniae

2004-01-01

Erektsioonihäirete põhjustest, seotud haigustest ja ravimeetoditest rääkisid ravimifirma Eli Lilly korraldatud loengupäeval uroloog Margus Punab, kardioloog Arvo Rosenthal, psühhiaater Imre Rammul ja Eli Lilly turundusjuht Katrin Lätt

Veiko Õunpuu polutshit premiju ot ES

Index Scriptorium Estoniae

2008-01-01

Cannes'i filmifestivali raames toimuval Euroopa päeval antakse filmirežissöör Veiko Õunpuule üle Euroopa Talendi auhind (European Talent Prize) mängufilmiprojekti "Püha Tõnu Kiusamine" eest (produtsent Katrin Kissa)

Õunpuu saab Euroopa Talendi auhinna / Kristiina Davidjants

Index Scriptorium Estoniae

Davidjants, Kristiina, 1974-

2008-01-01

Cannes'i filmifestivali raames toimuval Euroopa päeval antakse filmirežissöör Veiko Õunpuule üle Euroopa Talendi auhind (European Talent Prize) mängufilmiprojekti "Püha Tõnu Kiusamine" eest (produtsent Katrin Kissa)

Veiko Õunpuu astub Cannes'is punasele vaibale

Index Scriptorium Estoniae

2008-01-01

Cannes'i filmifestivali raames toimuval Euroopa päeval antakse filmirežissöör Veiko Õunpuule üle Euroopa Talendi auhind (European Talent Prize) mängufilmiprojekti "Püha Tõnu Kiusamine" eest (produtsent Katrin Kissa)

Biennaalitsirkus, biennaalileib / Katrin Kivimaa

Index Scriptorium Estoniae

Kivimaa, Katrin, 1969-

2007-01-01

52. Veneetsia biennaalist. Eesti paviljonis esineb Marko Mäetamm näitusega "I love my family". Lähemalt prantsuse kunstniku Sophie Calle ja inglise kunstniku Tracey Emini töödest. Hiina kunstnike Yang Fudongi filmist "Seitse intellektuaali bambusmetsas" ja Yang Zhenzhongi videoinstallatsioonist "I Will Die"

Naiste maailm / Katrin Rajasaare

Index Scriptorium Estoniae

Rajasaare, Katrin

2001-01-01

Pimedate Ööde V filmifestivalil näidatavast kolmest mängufilmist : Stefan Jägeri "Sünnipäev", Saksamaa 2001; Catherine Corsini "Proov", Prantsusmaa 2001; Rakhsan Bani Etemad "Linna kesta all", Iraan 2001

Rock kinoekraanil / Katrin Rajasaare

Index Scriptorium Estoniae

Rajasaare, Katrin

2008-01-01

7.-11. juulini kinos Sõprus toimuval filminädalal "Rock On Screen" ekraanile jõudvatest rockmuusikuid portreteerivatest filmidest "Lou Reed's Berlin", "The Future Is Unwritten: Joe Strummer", "Control: Joy Division", "Hurriganes", "Shlaager"

Katrin Denev pokazala harakter

Index Scriptorium Estoniae

2006-01-01

Veneetsia 63. filmifestivali auhinnatutest, kellest vaid Stephen Frears'i filmis "Kuninganna" ("The Queen") peaosa kehastanud Helen Mirren oli üks favoriitidest. Parima filmi peaauhind Kuldlõvi läks üllatuslikult Hiina režissööri Jia Zhang-Ke filmile "Vaikelu" ("Dong"). Ka teistest Veneetsia 63. filmifestivali võitjatest. Festivali žüriid juhatas Catherine Deneuve

Näitused / Katrin Kurik

Index Scriptorium Estoniae

Kurik, Katrin

1998-01-01

Linnagalerii Tallinnas: Anna Pauli tekstiilid ja Andras Huberi skulptuurid (Ungari); Kullo lastegalerii: Heli Männi ja Tondiraba keskkooli kunstiklasside õpilaste "Veneetsia maskid"; Tammsaare majamuuseum: Kersti Karu keraamika

Teistmoodi pulmafotod / Katrin Ruus

Index Scriptorium Estoniae

Ruus, Katrin

2009-01-01

Traditsioonilistest ja ebatraditsioonilistest tähtpäevafotodest. Dmitri Kotjuhi pildistatud pulmafotodest, kus on katsetatud erinevate keskkondadega. Tema fotosid on eksponeeritud näitusel "Argipäeva hetked"

EITSA teatab / Katrin Pink

Index Scriptorium Estoniae

Pink, Katrin

2005-01-01

Eesti Infotehnoloogia Sihtasutuse konkursist "Mobiilsustoetused - ITK erialade doktorantide mobiilsus", mille eesmärgiks on toetada Eesti avalik-õiguslike ülikoolide info- ja kommunikatsioonitehnoloogia erialade doktorantide osavõttu erialastest konverentsidest, täienduskursustest, suve- ja talvekoolidest välisriikides

Kas meediatsirkus? / Katrin Kivimaa

Index Scriptorium Estoniae

Kivimaa, Katrin, 1969-

2006-01-01

Turner Prize'i 2006. a. kunstipreemia näitusest Londonis Tate-Britainis. Nominente oli neli: Tomma Abts, Mark Titchner, Phil Collins ja Rebecca Warren. Preemia pälvis saksa-inglise maalikunstnik Tomma Abts. Pikemalt Phil Collinsi videost "Reaalse naasmine"

Barcelona Biennaalid / Katrin Koov

Index Scriptorium Estoniae

Koov, Katrin, 1973-

2006-01-01

Euroopa maastikuarhitektuuri biennaalist teemal "Landscape: a product - a production". 2003. a. Rosa Barba eripreemia pälvis laviinitõke Islandil (Reynir Vilhjalmsson), 2006. a. võidutööd: Pedra Tosca park Gironas (RCR Arhitektid), tööstusmaastikule loodud park-märgala (David Verport). Euroopa avaliku linnaruumi preemia konkursist võtsid esmakordselt osa eestlased nelja tööga (Rakvere keskväljak, Tubina mälestusmärk Tartus, trepp Rakvere Vallimäele, KUMU kompleks). Võitsid Horvaatia töö Morske Orgulje (Zadar), arhitekt Nikola Basic ja Hollandi töö A8ernA (Zaanstad), autor NL Architects

Vaba aja keskus Tasku = Tasku centre

Index Scriptorium Estoniae

2009-01-01

Tasku kompleksi Tartus Turu t. 2 projekteeris Arhitektuuribüroo Kalle Rõõmus. Tasku kaubandus- ja konverentsikeskuse sisekujundusest. Sisearhitektid Argo Vaikla, Katrin Vaikla, Mari-Liis Süld ja Liis Tarbe. Sisearhitektide tähtsamate tööde loetelu

Arstide koolitus vaakumis / Triin Tabur

Index Scriptorium Estoniae

Tabur, Triin

2014-01-01

Arstide täienduskoolituse fondi tulumaksusoodustustega ühenduste nimekirjast välja jätmine on arstide erialase täienduskoolituse välismaal jätnud stipendiumiteta. Selgitusi jagavad Katrin Rehemaa, Margus Viigimaa, Tiina Sats ja Toomas Pruunsild

Tallinna Tehnikakõrgkooli Arhitektuuri Instituudi rahvusvaheline töötuba 8.-12. september 2008

Index Scriptorium Estoniae

2009-01-01

Töötoa "Linnamaastik / Roheline Tallinn" teemad: "Tuukri park", "Vanalinna bastionite rohevöönd", "Teatriväljak", juhendajad: maastikuarhitekt Günter Nagel (Saksamaa), arhitektid Irina Raud ja Katrin Vannas, maastikuarhitekt Tiina Tuulik . Osalesid 4. kursuse arhitektuuri eriala tudengid

Pühapäeva õhtul uues Haabersti vabaajakeskuses = Sunday evening at the new Haabersti recreational centre / Kadri Vaher, Regina Viljasaar

Index Scriptorium Estoniae

Vaher, Kadri

2007-01-01

Arhitekt: Arhitektid Muru & Pere. Autorid: Urmas Muru, Peeter Pere. Sisekujundus: Katrin Kaevats, AB Muru & Pere. Konstruktor Rein Üts. Projekt: 2000, valmis: 2006. Ill.: II korruse plaan, lõige, 4 värv. välis- ja 2 sisevaadet

Klaasist, betoonist ja üllast ideest / Piret Veigel

Index Scriptorium Estoniae

Veigel, Piret, 1961-

2003-01-01

Sisearhitektide Argo ja Katrin Vaikla kodu. Looduslähedusest, ruumilahendusest ja materjalikasutusest. Puituksed, köögi aknaalune kapp ja söögilaud valmistati A. ja K. Vaikla jooniste järgi firmas Disekt. Välisvaade, 13 sisevaadet

Uue tantsu Superinimene / Ivar Põllu

Index Scriptorium Estoniae

Põllu, Ivar

2007-01-01

Festivalil "Uue tantsu nädal Tartus " esitatud viiest autorilavastusest : Katrin Essensoni "Manusega mõtted", Renate Valme "Mesta", Mart Kangro "Start. Based on a True Story", Kaja Kannu "There are Laika Dogs living in Estonia" ja Marten Spangbergi "Heja Sverige"

Nädal pakub kolme näituse jagu eesti nüüdisaegset kunsti / Mart Niineste

Index Scriptorium Estoniae

Niineste, Mart, 1983-

2011-01-01

Mihkel Kleisi uusima maaliloomingu näitus "Guts´n´Roses" Tallinnas Hobusepea galeriis. Graafik Silvi Liiva näitus "Piirideta" Tallinna Kunstihoone galeriis. Katrin ja Peeter Pere ühisnäitus "Laoseis" Tallinnas Tõnismäel Parikase majas

Hotell Hilton Tallinn Park / Kersti Pikk

Index Scriptorium Estoniae

Pikk, Kersti

2016-01-01

Äriklassihotellide ketti Hilton kuuluv hotell Tallinnas. Arhitektuurse lahenduse autor Meelis Press. Interjööri kujundasid Soome büroo dSign Vertti Kivi & Co ja Allianss Arhitektid. Hotelli tube ja üldalasid kaunistavad Katrin Karu ja Maria Simsoni maalid

"Backdoor" kunstnikku testimas / Rael Artel

Index Scriptorium Estoniae

Artel, Rael, 1980-

1999-01-01

Festival "Backdoor media'99" alapealkirjaga 'Fassaadid kodututele' Tallinnas. Performance Tammsaare monumendi juures (kuraator Hanno Soans), Silja Saarepuu video kerjamiskarpidest, Andrus Kõresaare ja Jouni Partaneni videod kerjustest, Marko Raadi dokumentaalfilm 'Esteetilistel põhjustel' (peaosas Andres Kurg), tekstikogumik ehk samizdat (toimetaja Katrin Kivimaa).

"Interstanding 3" põlgab trendi ja mainstream'i

Index Scriptorium Estoniae

1999-01-01

Kolmas rahvusvaheline meediakunsti festival "Interstanding 3", mille teema on "Ülalpool piire". Selle raames Kaasaegse Kunsti Eesti Keskuse 6. aastanäitus, loengud, konverents "Ülalpool piire". Esinevad Saskia Sassen Chicagost, Katrin Kivimaa, Ando Keskküla, Eric Kluitenberg Amsterdamist.

Islandi-elamus

Index Scriptorium Estoniae

2008-01-01

Galeriis SooSoo on müügil islandi noorte disainerite tööd: Gudrun Lilja Gunnlaugsdottiri laserlõiketehnoloogias raamaturiiulid "Fairytale", Ingibjörg Hanna Bjarnadottiri riidepuud "Raven", Tinna Gunnarsdottiri kummist laualinikud "Samurai", Katrin Olina riidenagid "Tree" ja portselannõud

Immuunsus ja sanatoorium

Index Scriptorium Estoniae

Jõgeva, Sandra, 1976-

2009-01-01

Katrin Murbachi (Šveits) & Riikka Tauriaineni (Soome) näitus "Sanatoorium" Tallinna Linnagaleriis 2. augustini. Rühmituse Noolegrupp liikmete Triinu Jürvese ja Villem Jahu videoinstallatsioon "Immunity Summary and the Outside World" ("Immuunsuse kokkuvõte ja sealpoolne maailm") Kultuurikatlas 24. juulil

Hitler, Stalin ja Vana Toomas koos / Helen Eelrand

Index Scriptorium Estoniae

Eelrand, Helen, 1971-

2004-01-01

Ajalooliste esemete, eelkõige kommunistliku ja natsionaalsotsialistliku sümboolika müügist. Kommentaarid Riigikogu liikmelt Helir-Valdor Seederilt, okupatsioonimuuseumi töötajalt Rasmus Rausbergilt ja siseministeeriumi pressinõunikult Katrin Videselt. Lisa: Lenin läheb idablokis kaubaks

Kuldma, Aus, Roosma ja Siska

Index Scriptorium Estoniae

2007-01-01

2006. aasta Kuldnõela võitja kuulutatakse välja Tallinnas Viru keskuses 9.03.2007. Kandidaadid Katrin Kuldma kollektsiooniga Chocolate, Reet Aus kaubamärgiga Re Use, Tiiu Roosma pesukollektsiooniga BonBon Lingerie ja Marika Siska kaubamärgiga Sangar

1 küsimus noorele juhile : Mis teha, kui kopp on ees - kuidas sa stressist jagu saad? / Riho Jürvetson, Merit Miller, Krister Rekkaro ... [jt.

Index Scriptorium Estoniae

2009-01-01

Küsimusele vastavad EMT erakliendi osakonna juhataja Riho Jürvetson, KPMG Baltics müügijuht Merit Miller, ArtPrint juht Krister Rekkaro, Dateli juhatuse liige Triin Sepp, Media House projektijuht Tanel Tarkmees, Ober-Haus Kinnisvara tegevjuht Katrin Klein-Näppi

18. XII kell 12 kaitstakse EKA E-meedia keskuses 4 magistritööd...

Index Scriptorium Estoniae

2002-01-01

Kristel Sibul "Kehatud kehad - kehad ja identiteet internetis" (juh. Katrin Kivimaa), Ivika Kivi "Virtuaalsed õpitarkvarad" (juh. Mare Emmott Tralla), Maris Lindoja "Digitaalne ruum" (juh. Andres Kurg), Raul Keller "Corporate Consulting in the Digital Age - Jamming vith the Culture" (juh. Richard Barbrook)

Tähtis on hoida ühtset joont / Agne Adamson

Index Scriptorium Estoniae

Adamson, Agne

2011-01-01

Eesti Perearstide Seltsi 2008. a. valitud juhatuse tööst kolme aasta vältel ning tulevikuvisioonidest. Vestlusringis osalesid Ruth Kalda, Diana Ingerainen, Madis Tiik, Eret Jaanson, Anneli Talvik, Katrin Martinson ja Külvi Peterson. Kommentaarid EPS-i liikmetelt

Orizzonti medal pole kehvem Kuldlõvist / Alo Paistik

Index Scriptorium Estoniae

Paistik, Alo

2007-01-01

Eesti mängufilm "Sügisball" (režissöör Veiko Õunpuu, produtsent Katrin Kissa) sai Venezia 64. filmifestivali konkursiprogrammi Orizzonti peaauhinna. Filmi delegatsiooni (V. Õunpuu, R. Tolk, M. Jakobson, K. Kissa) esinemisest ja vastuvõtust festivalil

The expression of genes involved in the ergosterol biosynthesis pathway in Candida albicans and Candida dubliniensis biofilms exposed to fluconazole.

LENUS (Irish Health Repository)

2009-03-01

The expression of the ERG1, ERG3, ERG7, ERG9, ERG11 and ERG25 genes in response to incubation with fluconazole and biofilm formation was investigated using reverse-transcription PCR and real-time PCR in Candida albicans and Candida dubliniensis clinical isolates. The viability of biofilm was measured using an 2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT) reduction assay and confocal scanning laser microscopy (CSLM). Expression of the ERG11 gene was found to be low or moderate and it was regulated by fluconazole addition more so than by biofilm formation. Very low or non-detectable expression of ERG1, ERG7 and ERG25 genes was detected in C. albicans. The expression of the ERG9 increased in the presence of fluconazole in some isolates. Following incubation with fluconazole, formation of biofilm by C. dubliniensis was coupled with up-regulation of the ERG3 and ERG25 genes as have been observed previously in C. albicans. Planktonic cells of both Candida species released from biofilm displayed similar resistance mechanisms to fluconazole like attached cells. The XTT reduction assay and CSLM revealed that although incubation with fluconazole decreased the biofilm thickness, these were still comprised metabolically active cells able to disseminate and produce biofilm. Our data indicate that biofilm represents a highly adapted community reflecting the individuality of clinical isolates.

Art and Identity : The Soviet Woman in Estonian Art / Michael Schwab

Index Scriptorium Estoniae

Schwab, Michael, 1966-

2010-01-01

Kumu Kunstimuuseumis 8.04.-26.09.2010 avatud näitusest "Nõukogude naine eesti kunstis", kuraatorid Katrin Kivimaa ja Kädi Talvoja. Ernst Hallopi maalist "Piimatootmine Väimela karjandustehnikumis" (1948) ja Lola Liivati maalist "Laulja ja näitleja Elo Tamuli portree" (1954)

Ülemiste kaubanduskeskus = Ülemiste shopping center / Priit Põldme ; kommenteerinud Linda Madalik

Index Scriptorium Estoniae

Põldme, Priit, 1971-

2015-01-01

Ülemiste kaubanduskeskus Tallinnas Suur-Sõjamäe 4. Sisekujunduse autorid Priit Põldme, Reet Sepp (sisearhitektuuribüroo Joonprojekt); arhitektid Einar Aakeroy (AMB Arkitekter), Lauri Laisaar, Ingel Sirkel-Suviste, Jaanika Oks, Katrin Kõlu (Novarc Group AS). Lühidalt Priit Põldmest ja Reet Sepast

Kanuti gildi saalis jätkub performance'i-festival "Continental Breakfast Tallinn NU performance" : ...

Index Scriptorium Estoniae

2005-01-01

12. XI Eva Meyer-Kelleri (Saksamaa/Rootsi) etendus "Surm on kindel/Death is Certain". Performance'i esitab Irina Müller. 14. XI esitab Kim H. Veltman (Kanada/Holland) performance'i "Maailmapuu/World Tree". 15. XI Katrin Essensoni etendus "Designed to make Difference"

Ruudi läheb Tokyosse / Olev Remsu

Index Scriptorium Estoniae

Remsu, Olev, 1947-

2006-01-01

Lastefilm "Ruudi" : stsenaristid Aare Toikka, Aarne Mägi : režissöör Katrin Laur : nimiosas lapsnäitleja Paul Oskar Soe : operaator Rein Kotov : Allfilm - MRP Matila Röhr Productions - Schmidtz Katze Filmkollektiv 2006. Lähemalt analüüsitakse stsenaariumi

A GLIMPSE INTO THE EYE OF THE EMERGENCY RESPONSE AT EPA KATRINA AND RITA

Science.gov (United States)

This presentation was given at the Texas Environmental Health Association Annual Meeting in Round Rock, TX on October 12, 2005. The keynote address was focused on the conditions after Katrins, organizing response, field response, EPA's role in emergency response, what is EPA doi...

Võru linnagaleriis avati kolm uut näitust

Index Scriptorium Estoniae

2009-01-01

26. oktoobrist 20 novembrini on Võru Linnagaleriis avatud Ruti Jõgi joonistuste ja Aivar Rumvoldi maalide näitus "Koos. Omaette", Marek Hämmelbergi isikunäitus "Tuvi ämm" ning grupi Sigmund Freud (Liina Guiter, Katrin Tees, Helen Melesk) näitus "Keemia"

Gating mechanism of Kv11.1 (hERG) K+ channels without covalent connection between voltage sensor and pore domains.

Science.gov (United States)

de la Peña, Pilar; Domínguez, Pedro; Barros, Francisco

2018-03-01

Kv11.1 (hERG, KCNH2) is a voltage-gated potassium channel crucial in setting the cardiac rhythm and the electrical behaviour of several non-cardiac cell types. Voltage-dependent gating of Kv11.1 can be reconstructed from non-covalently linked voltage sensing and pore modules (split channels), challenging classical views of voltage-dependent channel activation based on a S4-S5 linker acting as a rigid mechanical lever to open the gate. Progressive displacement of the split position from the end to the beginning of the S4-S5 linker induces an increasing negative shift in activation voltage dependence, a reduced z g value and a more negative ΔG 0 for current activation, an almost complete abolition of the activation time course sigmoid shape and a slowing of the voltage-dependent deactivation. Channels disconnected at the S4-S5 linker near the S4 helix show a destabilization of the closed state(s). Furthermore, the isochronal ion current mode shift magnitude is clearly reduced in the different splits. Interestingly, the progressive modifications of voltage dependence activation gating by changing the split position are accompanied by a shift in the voltage-dependent availability to a methanethiosulfonate reagent of a Cys introduced at the upper S4 helix. Our data demonstrate for the first time that alterations in the covalent connection between the voltage sensor and the pore domains impact on the structural reorganizations of the voltage sensor domain. Also, they support the hypothesis that the S4-S5 linker integrates signals coming from other cytoplasmic domains that constitute either an important component or a crucial regulator of the gating machinery in Kv11.1 and other KCNH channels.

The particle tracking package Kassiopeia

Energy Technology Data Exchange (ETDEWEB)

Groh, Stefan [Karlsruhe Institute of Technology (Germany); Collaboration: KATRIN-Collaboration

2016-07-01

The Kassiopeia particle tracking framework is an object-oriented software package utilizing modern C++ techniques, written originally to meet the needs of the Katrin collaboration. Kassiopeia's target consists of simulating particle trajectories governed by arbitrarily complex differential equations of motion, continuous physics processes that may in part be modeled as terms perturbing that equation of motion, stochastic processes that occur in flight such as bulk scattering and decay, and potentially stochastic surface processes occurring at interfaces, including transmission and reflection effects. This entire set of computations takes place against the backdrop of a fully-featured geometry package which serves a variety of roles, including initialization of electromagnetic field simulations, gas flow simulations, and the support of state-dependent algorithm-swapping and behavioral changes. Kassiopeia has been well validated and widely used within the Katrin collaboration, playing a primary role in many theses and refereed publications.

Acute and Chronic Toxicity, Cytochrome P450 Enzyme Inhibition, and hERG Channel Blockade Studies with a Polyherbal, Ayurvedic Formulation for Inflammation

Directory of Open Access Journals (Sweden)

Debendranath Dey

2015-01-01

Full Text Available Ayurvedic plants are known for thousands of years to have anti-inflammatory and antiarthritic effect. We have recently shown that BV-9238, a proprietary formulation of Withania somnifera, Boswellia serrata, Zingiber officinale, and Curcuma longa, inhibits LPS-induced TNF-alpha and nitric oxide production from mouse macrophage and reduces inflammation in different animal models. To evaluate the safety parameters of BV-9238, we conducted a cytotoxicity study in RAW 264.7 cells (0.005–1 mg/mL by MTT/formazan method, an acute single dose (2–10 g/kg bodyweight toxicity study and a 180-day chronic study with 1 g and 2 g/kg bodyweight in Sprague Dawley rats. Some sedation, ptosis, and ataxia were observed for first 15–20 min in very high acute doses and hence not used for further chronic studies. At the end of 180 days, gross and histopathology, blood cell counts, liver and renal functions were all at normal levels. Further, a modest attempt was made to assess the effects of BV-9238 (0.5 µg/mL on six major human cytochrome P450 enzymes and 3H radioligand binding assay with human hERG receptors. BV-9238 did not show any significant inhibition of these enzymes at the tested dose. All these suggest that BV-9238 has potential as a safe and well tolerated anti-inflammatory formulation for future use.

Molecular determinants of interactions between the N-terminal domain and the transmembrane core that modulate hERG K+ channel gating.

Directory of Open Access Journals (Sweden)

Jorge Fernández-Trillo

Full Text Available A conserved eag domain in the cytoplasmic amino terminus of the human ether-a-go-go-related gene (hERG potassium channel is critical for its slow deactivation gating. Introduction of gene fragments encoding the eag domain are able to restore normal deactivation properties of channels from which most of the amino terminus has been deleted, and also those lacking exclusively the eag domain or carrying a single point mutation in the initial residues of the N-terminus. Deactivation slowing in the presence of the recombinant domain is not observed with channels carrying a specific Y542C point mutation in the S4-S5 linker. On the other hand, mutations in some initial positions of the recombinant fragment also impair its ability to restore normal deactivation. Fluorescence resonance energy transfer (FRET analysis of fluorophore-tagged proteins under total internal reflection fluorescence (TIRF conditions revealed a substantial level of FRET between the introduced N-terminal eag fragments and the eag domain-deleted channels expressed at the membrane, but not between the recombinant eag domain and full-length channels with an intact amino terminus. The FRET signals were also minimized when the recombinant eag fragments carried single point mutations in the initial portion of their amino end, and when Y542C mutated channels were used. These data suggest that the restoration of normal deactivation gating by the N-terminal recombinant eag fragment is an intrinsic effect of this domain directed by the interaction of its N-terminal segment with the gating machinery, likely at the level of the S4-S5 linker.

Premixing hydrogen burners for surface refinement of glass; Vormischende Wasserstoffbrenner zur Oberflaechenbearbeitung von Glas

Energy Technology Data Exchange (ETDEWEB)

Goerisch, Matthias [Linde AG, Linde Gas Deutschland, Nuernberg (Germany)

2013-02-15

As a result, inter alia, of unceasing globalisation, European glass producers in practically all sectors - flat glass, container glass, crystal glass and special glasses - are faced with ever tougher competition from Asia. In the 2012 to 2015 period and beyond, the principal focuses in the manufacture of glass products will again be on reducing overall production costs and increasing process efficiency wherever possible, on greater productivity and on enhanced product (surface) quality. To meet these challenges in the field of surface refinement and flame polishing of glass products as efficiently as possible, Linde AG/Linde Gases Division has developed premixing Hydropox {sup registered} burner technology for hydrogen/oxygen fuels. (orig.)

Slipstream pilot-scale demonstration of a novel amine-based post-combustion technology for carbon dioxide capture from coal-fired power plant flue gas

Energy Technology Data Exchange (ETDEWEB)

Krishnamurthy, Krish R. [Linde LLC, Murray Hill, NJ (United States)

2017-02-03

Post-combustion CO₂ capture (PCC) technology offers flexibility to treat the flue gas from both existing and new coal-fired power plants and can be applied to treat all or a portion of the flue gas. Solvent-based technologies are today the leading option for PCC from commercial coal-fired power plants as they have been applied in large-scale in other applications. Linde and BASF have been working together to develop and further improve a PCC process incorporating BASF’s novel aqueous amine-based solvent technology. This technology offers significant benefits compared to other solvent-based processes as it aims to reduce the regeneration energy requirements using novel solvents that are very stable under the coal-fired power plant feed gas conditions. BASF has developed the desired solvent based on the evaluation of a large number of candidates. In addition, long-term small pilot-scale testing of the BASF solvent has been performed on a lignite-fired flue gas. In coordination with BASF, Linde has evaluated a number of options for capital cost reduction in large engineered systems for solvent-based PCC technology. This report provides a summary of the work performed and results from a project supported by the US DOE (DE-FE0007453) for the pilot-scale demonstration of a Linde-BASF PCC technology using coal-fired power plant flue gas at a 1-1.5 MWe scale in Wilsonville, AL at the National Carbon Capture Center (NCCC). Following a project kick-off meeting in November 2011 and the conclusion of pilot plant design and engineering in February 2013, mechanical completion of the pilot plant was achieved in July 2014, and final commissioning activities were completed to enable start-up of operations in January 2015. Parametric tests were performed from January to December 2015 to determine optimal test conditions and evaluate process performance over a variety of operation parameters. A long-duration 1500-hour continuous test campaign was performed from May to

Vanilla Ninjast saab vene bänd / Viktoria Ladõnskaja

Index Scriptorium Estoniae

Ladõnskaja, Viktoria, 1981-

2007-01-01

Plaadifirmalt Topten Vanilla Ninja lepingu ära ostnud jurist Aleksander Simakov kuulutab välja konkursi bändi uute tüdrukute leidmiseks, bänd koosseisus Piret Järvis, Lenna Kuurmaa ja Katrin Siska kavatsevad ka Vanilla Ninja nime all jätkata

Tuult tiibadesse

Index Scriptorium Estoniae

Mikomägi, Margus, 1956-

2009-01-01

Autori arvates on 2009. a. suve teatripildis selline etendus, millel on pikk järelmõju, Katrin Saukase kirjutatud ja lavastatud lugu "Tuult tiibadesse", mida mängiti Hüüru mõisas, ühenduse R.A.A.A.M. eestvõtmisel ja toel

Mida sina täna õppisid? / Veikko Täär, Ain Aaviksoo, Ingrid Tõniste ... [jt.

Index Scriptorium Estoniae

2012-01-01

Oma õppimistest ja tulevikuplaanidest räägivad näitleja ja ettevõtja Veikko Täär, tervishoiuteadlane Ain Aaviksoo, tegevjuht Ingrid Tõniste, TV3 avalike suhete juht ja uudisteankur Anneli Adermann, arenduskonsultant Anu Puusaag, personaaltreener Katrin Pärt ja loodusarst Tiina Keldrima

Parimad Eesti modellid / Mari-Liis Helvik

Index Scriptorium Estoniae

Helvik, Mari-Liis

2008-01-01

Kersti Pedanik, Martin Merimaa agentuurist Living Models Agency; Olga Serova, Anett Griffel agentuurist EMA Model Management; Triin Villemsaar, Kertu-Maria Nurk agentuurist Beatrice MASS Modelnet; Karmen Pedaru, Carolina Bergstein agentuurist MJ-Models. Kommenteerivad Evelyn Mikomägi, Katrin Rannaväli, Beatrice, Margit Jõgger

Kaitseväelastel pole alust kogu missiooni eest lisapalka nõuda / Holger Roonemaa

Index Scriptorium Estoniae

Roonemaa, Holger

2007-01-01

Afganistanis teeninud kolm Eesti kaitseväelast nõuavad kaitseväelt Tallinna halduskohtus igaüks enam kui poolt miljonit krooni. Tööõigusbüroo Labour Consulting juristi Katrin Sarapi sõnul pole selliseks nõudeks alust. Vt. samas: Rahanõudjad teenivad edasi

Eesti Metodisti Kirik : Balti Misjoni Keskus, Narva mnt. 51, Tallinn = Estonian Methodist Church / Vilen Künnapu

Index Scriptorium Estoniae

Künnapu, Vilen, 1948-

2000-01-01

Projekteerija Arhitektuuribüroo Künnapu & Padrik. Arhitektid Vilen Künnapu, Ain Padrik. Konstruktsioonide autor Andres Laur. Sisekujundajad Argo ja Katrin Vaikla. Projekt 1994, valmis 2000. Kirik on klaasja pikliku koolitiivaga (teoloogiline seminar). 7 ill.: I korruse plaan, lõige, välis- ja sisevaated

Moda vernulas v Tallin / Marina Poltavtseva

Index Scriptorium Estoniae

Poltavtseva, Marina

2005-01-01

Tallinnas Viru Keskuses toimuvast moeürituste sarjast FIBIT. Keskne sündmus on Kuldnõela nominentide Katrin Kuldma, Tiina Talumehe, Thea Pilveti ja Evelin Lille kollektsioonide esitamine. Lisas "Primetshai marku!" juttu moekunstnik Oksana Tanditi uuest kollektsioonist, mida näidatakse ka Viru keskuses

Keelesümpoosion arutas Põhjamaade mõistet / Ülo Ignats ; fotod: Ülo Ignats

Index Scriptorium Estoniae

Ignats, Ülo, 1951-2011

2006-01-01

Stockholmis Riigipäeva teise koja saalis teemal "Kuivõrd põhjamaine on Baltikum". Ettekannetega esinesid: Kristel Zilmer, Battail, Jean-Francois Battail, Torkel Jansson, Madis Kanarbik, Stig Örjan Ohlsson, Ivars Orehovs, Erika Sausverde, Thomas Lundén, Katrin Maandi, Kristel Kääramees

Vabaduse väljaku ümberkujundamise ideekonkurss

Index Scriptorium Estoniae

1998-01-01

2. märtsil lõppenud Vabaduse väljaku ideekonkursil II preemia saanud Andres Alveri, Tiit Trummali ja Veljo Kaasiku tööst 'Pietro del Primo' ning III preemia saanud Margit Mutso, Madis Eegi ja Katrin Koovi tööst 'Varsti valge'.