Science.gov

Sample records for 2b holzpellets und

  1. Fit 2-B FATHERS.

    ERIC Educational Resources Information Center

    Maiorano, Joseph J.

    2001-01-01

    Fit 2-B FATHERS is a parenting-skills education program for incarcerated adult males. The goals of this program are for participants to have reduced recidivism rates and a reduced risk of their children acquiring criminal records. These goals are accomplished by helping participants become physically, practically, and socially fit for the demands…

  2. Boeing XF2B-1 (F2B-1)

    NASA Technical Reports Server (NTRS)

    1931-01-01

    Boeing XF2B-1 (F2B-1): Serving as the prototype for the F2B-1 shipboard fighter, the XF2B-1 differed visually in having a pointed spinner and an unbalanced rudder. Like many aircraft of its day, the Boeing model 69 was powered by a Pratt & Whitney Wasp radial engine.

  3. SACALC2B

    Energy Science and Technology Software Center (ESTSC)

    2007-02-08

    SACALC2B calculates the average solid angle subtended by a rectangular or circular detector window to a coaxial or non-coaxial rectangular, circular or point source, including where the source and detector planes are not parallel. SACALC_CYL calculates the average solid angle subtended by a cylinder to a rectangular or circular source, plane or thick, at any location and orientation. This is needed, for example, in calculating the intrinsic gamma efficiency of a detector such as amore » GM tube. The program also calculates the number of hits on the cylinder side and on each end, and the average path length through the detector volume (assuming no scattering or absorption). Point sources can be modelled by using a circular source of zero radius.« less

  4. Pancreatic Cancer Stage 2B

    MedlinePlus

    ... 2B Description: Stage IIB pancreatic cancer; drawing shows cancer in the pancreas and in nearby lymph nodes. Also shown are the bile duct, pancreatic duct, and duodenum. Stage IIB pancreatic cancer. Cancer has spread to nearby lymph nodes and ...

  5. Peginterferon Alfa-2b Injection (Sylatron)

    MedlinePlus

    ... injection is in a class of medications called interferons. It works by stopping the growth of cancer ... allergic to peginterferon alfa-2b injection (PegIntron, Sylatron), interferon alfa-2b (Intron), any other medications, or any ...

  6. Investigation of Class 2b Trucks

    SciTech Connect

    Davis, S.C.

    2002-04-03

    The popularity of trucks in the class 2 category--that is, those with a 6,000 to 10,000 pounds (lbs) gross vehicle weight rating (GVWR)--has increased since the late 1970s/early 1980s. The purpose of this research is to identify and examine vehicles in the upper portion of the class 2 weight range (designated as vehicle class 2b) and to assess their impact. Vehicles in class 2b (8,500-10,000 lbs GVWR) include pickup trucks, sport utility vehicles (SUVs), and large vans (i.e., not minivans). Oak Ridge National Laboratory researched each individual truck model to determine which models were class 2b trucks and arrived at four methodologies to derive sales volumes. Two methods--one for calendar year and one for model year sales--were recommended for producing believable and reliable results. The study indicates that 521,000 class 2b trucks were sold in calendar year 1999--6.4% of sales of all trucks under 10,000 lbs. Eighty-two percent of class 2b trucks sold in 1999 were pickups; one third of class 2b trucks sold in 1999 were diesel. There were 5.8 million class 2b trucks on the road in 2000, which amounts to 7.8% of all trucks under 10,000 lbs. Twenty-four percent of the class 2b truck population is diesel. Estimates show that class 2b trucks account for 8% of annual miles traveled by trucks under 10,000 lbs and 9% of fuel use. Data on class 2b trucks are scarce. As the Tier 2 standards, which apply to passenger vehicles in the 8,500-10,000 lb GVWR category, become effective, additional data on class 2b trucks may become available--not only emissions data, but data in all areas. At the moment, distinguishing class 2b trucks from class 2 trucks in general is a substantial task requiring data on an individual model level.

  7. Branchen und Unternehmensbereiche

    NASA Astrophysics Data System (ADS)

    Kramer, Regine

    Dieses Kapitel gibt einen Überblick über die Haupteinsatzgebiete von Mathematikern, Informatikern, Naturwissenschaftlern und Ingenieuren in den wichtigsten Wirtschaftsbranchen und Unternehmensbereichen. Dabei werden ausbildungsnahe Aufgabenbereiche ebenso beschrieben wie eher fachferne Tätigkeiten und neben den klassischen Branchen und Berufsbildern auch neue Tätigkeitsfelder für MINT-Fachkräfte beschrieben.

  8. Peginterferon Alfa-2b Injection (Sylatron)

    MedlinePlus

    ... 2b injection is used in people with malignant melanoma (a life-threatening cancer that begins in certain ... is used to reduce the chance that malignant melanoma will come back and must be started within ...

  9. Peginterferon Alfa-2b (PEG-Intron)

    MedlinePlus

    ... inject into your stomach if you are very thin. Use a different spot for each injection. Do not inject peginterferon alfa-2b into an area where the skin is sore, red, bruised, scarred, irritated, or infected; has stretch marks ...

  10. Welt und Wirkungsprinzip

    NASA Astrophysics Data System (ADS)

    Landgraf, Werner

    1997-05-01

    Modell einer kausalen Bewirkung der Welt, und logische, geometrische, physikalische Interprätation dieser Kausalmenge und Fortwirkung der frühsten ihrer sukzessiv als echt Neues bewirkten und durch Vorhandenes oder Späteres nicht darstellbaren oder widerrufbaren Ereignisse als Dimensionen und sie verkörpernde primäre Naturkräfte, mit Korrespondenz zur beobachteten Welt und ihrer grundlegendsten Eigenschaften. Wirklich ist nur was wirkt, wo und wie. Entsprechend ist im Bogenelement statt der Eigenzeit die variante Anzahl Wirkungen relevant, 0 ≈ 1/h2 dS2 - 1/tpl2 (dt2 - 1/c2 {dq12 + G02/G2 [dq2,32 - ...]}) mit G0 = c4lpl/Epl ≈ G. Die heutigen Dimensionen und Naturkräfte entstanden in dieser Reihenfolge, haben 'komplementäre' aber gleichwertige statische und dynamische Aspekte, entsprechend ihren Termen in Bogenelement bzw. Vierervektor, aus derem Vergleich sowie mit denen ihrer Nachbarn folgen Grundgleichungen bzw. Erhaltungssätze. Jeweils individuelle Eigenschaften wie ihre Naturkonstante konkretisieren sie und tragen zu gattungsmäßigen wie globale Affinität und Äquivalenzen bei. Ältestes Gebiet oder räumlicher Rand jeder Dimension sind die ersten vom Vorgänger bewirkten Ereignisse, selbst raumzeitlicher Ursprung des Nachfolgers, dort einmalig und ewig maximal rotverschoben fortwirkend und nicht lokalisierbar, um neue Elementareinheiten verschieden und lichtartig mit deren Verhältnis oder dem ihrer globalen Zustandsgrößen als konstanten Anfangsimpuls, Expansion, Längen- oder Ereignisdichte zueinander. Der Übergang vom diskreten Modell weniger Informationen zum Kontinuum und die Korrespondenz zur Physik ist problemlos, Details wie ein kontinuierlicher, abrupter oder ganz fehlender Abfall der Metrik beim ältesten Gebiet sind aber nur durch Beobachtungen entscheidbar. Erörtert werden allgemeine und individuelle Eigenschaften und ihre Konsequenzen der Dimensionen mit ihren Kräften, selbst und im Verhältnis zueinander, etwa ihrer begrenzten

  11. Physikunterricht und Kalter Krieg

    NASA Astrophysics Data System (ADS)

    Rieß, Falk; Kremer, Armin

    Die Indienstnahme des Physikunterrichts für militaristische und politische Zwecke ist in Deutschland nichts Neues: Die Wurzeln liegen im Kaiserreich und im Faschismus ("Wehrphysik"), und die Praxis im Kalten Krieg stellt hier nichts Außergewöhnliches, sondern lediglich eine auffällige Kontinuität dar.

  12. What Happened with Spectrometer Magnet 2B

    SciTech Connect

    Green, Michael A

    2010-05-27

    The spectrometer solenoid is supposed to be the first magnets installed in MICE [1]-[4]. This report described what happened during the test of the MICE spectrometer solenoid 2B. First, the report describes the temperatures in the magnet, the cooler top plate and the shield during the run where the magnet quenched at 258 A. During this quench, a lead between the bottom of the HTS leads and the diode bank burned out causing the magnet to quench. Second, three methods for measuring the net heat flow into the cold mass are described. Third, there is a discussion of possible resistive heating in the HTS leads between liquid helium temperature and the copper plate, which is at about 50 K. Fourth, there is a discussion of the measured first stage heat loads in the magnet, when there is no current in the magnet. The first stage heat load calculations are based on knowing the first stage temperatures of the three two-stage pulse tube coolers and the single stage GM cooler. Fifth, the estimated heat load to the first stage when the magnet has current in it is discussed. Sixth, there is a comparison of the stage 1 heat loads in magnet 1A [5], magnet 2A [6], and magnet 2B [7]. Finally there is a discussion of recommended changes for improving the spectrometer solenoids so that the coolers can keep them cold.

  13. Telecom 2-B and 2-C (TC2B and TC2C)

    NASA Technical Reports Server (NTRS)

    Dulac, J.; Alvarez, H.

    1991-01-01

    The DSN (Deep Space Network) mission support requirements for Telecom 2-B and 2-C (TC2B and TC2C) are summarized. These Telecom missions will provide high-speed data link applications, telephone, and television service between France and overseas territories as a follow-on to TC2A. Mission objectives are outlined and the DSN support requirements are defined through the presentation of tables and narratives describing the spacecraft flight profile; DSN support coverage; frequency assignments; support parameters for telemetry, command and support systems; and tracking support responsibility.

  14. Geoinformation und Staat

    NASA Astrophysics Data System (ADS)

    Zypries, Brigitte

    2002-09-01

    Geoinformationen besaßen als Grundlage militärischer Interventionen schon immer einen hohen Stellenwert für den Staat. Im Zeitalter der modernen Informations- und Kommunikationstechnologien wächst in demokratischen Staaten die Bedeutung von Geodaten weit über den Verteidigungsbereich hinaus. Brigitte Zypries, Staatssekretärin im Bundesministerium des Innern (BMI) und Vorsitzende des Interministeriellen Ausschusses für Geoinformationswesen (IMAGI), sprach mit Dipl.-Geogr. Ute C. Bauerüber die Anwendung und Koordinierung von Geodaten in Politik und Staat.

  15. Roboter und Zuckerstangen

    NASA Astrophysics Data System (ADS)

    Siebert, Heike

    Bei Produktion und Logistik denkt man sofort an Fabriken, Lagerhallen und Gabelstapler und nicht unbedingt an Zellbiologie. Sieht man etwas genauer hin erscheint dieser Gedankensprung jedoch gar nicht mehr so unpassend. In einer lebenden Zelle laufen eine Vielzahl von Produktions-, Transport- und Regulationsprozessen ab. Soll etwa ein gerade verfügbarer Rohstoff abgebaut werden, muss vielleicht ein Signal ein Gen erreichen, das ein geeignetes Enzym kodiert. Die Aktivierung des Gens führt über mehrere Zwischenstationen zur Produktion des Enzyms, das schließlich noch dahin gelangen muss, wo es gebraucht wird. Ist der Bedarf gedeckt, muss wiederum die Enzymproduktion eingestellt werden.

  16. Sternbilder und ihre Mythen

    NASA Astrophysics Data System (ADS)

    Fasching, Gerhard

    Die Sternbilder, die seit alters her die Menschen in ihren Bann gezogen haben, und die damit verbundenen Mythen werden in zweifacher Weise vorgestellt. Erstens ist es die Absicht, dem Leser zu helfen, sich am Sternenhimmel zurechtzufinden, und zweitens will es ihm die Vielfalt der Bilder vermitteln, die damit verbunden sind. Am Anfang des Buches stehen die prächtigen Erzählungen aus Ovids Metamorphosen. Dann ist vom Sternenhimmel im Jahreskreis die Rede, um den Leser anzuregen, diesen fast unendlichen Bilderreichtum sich selbst durch eigene Beobachtungen zu erschließen. Ein umfangreicher Abschnitt behandelt die einzelnen Sternbilder und das hierzu überlieferte Wissen. Sternkarten und alte Kupferstiche aus dem Bestand der Österreichischen Nationalbibliothek zeigen, wie man sich in früheren Jahrhunderten den Sternenhimmel vorgestellt hat. Sternsagen und Mythen werden erzählt und auch das ptolemäische und das kopernikanische Weltsystem werden einander gegenübergestellt. Ausführliche Sachverzeichnisse mit über 3000 Suchbegriffen erleichtern den Zugang zu Stern- und Sternbildnamen und zur Mythologie.

  17. Integument und Anhangsorgane

    NASA Astrophysics Data System (ADS)

    Schliemann, Harald

    Das Integument umhüllt den Wirbeltierkörper lückenlos. In der embryonalen Mundbucht (Stomodaeum) und der Afterbucht (Proctodaeum) grenzt es an die Auskleidung des Darmrohres. Über die generelle Bedeutung einer Haut als Abgrenzung zwischen Körperinnenraum und Außenmedium hinaus hat es bei Schädeltieren ein breites Spektrum von Funktionen. Die wichtigsten sind: Mechanischer Schutz durch Verhornungen und Verknöch erungen; Wundheilung; Schutz vor Wasserverlust; Schutz vor Infektionen durch bakterizide Drüsensekrete und immunkompetente Zellen; Schutz vor kurzwelliger Strahlung durch Pigmente; Schutz vor Überwärmung durch Schweißdrüsensekrete und Schutz vor Wärmeverlust durch Federn und Haare; Ausbildung lokomotorisch wichtiger Strukturen wie Federn, Flug- und Schwimmhäute, Krallen und Hufe; Redukt ion des Strömungswiderstandes durch Dämpfungshaut; Abgabe von Sekreten zur Ernährung (Milch); Ausbildung von Strukturen zu Nahrungserwerb und_-bearbeitung, z. B. Zähne, Barten;

  18. Axial Magnetic Anisotropy from Two Systems Fe2B and Co2B with Planar Anisotropy

    NASA Astrophysics Data System (ADS)

    Taufour, Valentin; Lamichhane, Tej; Bud'Ko, Sergey L.; Jesche, Anton; Goldman, Alan I.; Dennis, Kevin W.; McCallum, R. William; Antropov, Vladimir; Canfield, Paul C.

    2015-03-01

    Growth of single crystals of (Fe1-xCox)2B (0 <= x <= 1) and detailed characterization of their magnetic properties will be presented. Despite the fact that both Fe2B and Co2B show a planar anisotropy at room temperature, we observe a uniaxial anisotropy at intermediate doping which makes (Fe,Co)2B a promising system for permanent magnet applications in a system without rare-earth element. Comparison with recent band structure calculations will be presented. The temperature dependence of the anisotropy measured on single crystals from 2 K to 1000 K shows some unusual variations with an increase of the magnetic anisotropy with increasing temperature at some specific substitution. This work is supported by the Critical Materials Institute, an Energy Innovation Hub funded by the US DOE and by the Office of Basic Energy Science, Division of Materials Science and Engineering. Ames Laboratory is operated for the US DOE by Iowa State University under Contract No. DE-AC02-07CH11358.

  19. Synthesis and Electrochemical Properties of Nano-VO2 (B).

    PubMed

    Yang, Yun; Lu, Yong; Wang, Wei; Feng, Chuanqi; Yang, Shuijin

    2016-03-01

    The nano-VO2 (B) has been self-assembly synthesized by hydrothermal method using different templates, which may give them some interesting properties. The as-prepared samples were characterized by X-ray powder diffraction (XRD) and scanning electron microscopy (SEM). The electrochemical properties of the samples were investigated. The results show that the hexadecyltrimethyl ammonium bromide (CTAB) (soft template) was used to obtain the VO2 (B1) nanobelts. The flake graphite (hard template) was taken to get the VO2 (B2) nanosheets. The VO2 (B1) nanobelts have higher initial capacity to compare with VO2 (B2). But the VO2 (B2) nanosheets showed better cycling performance than that of VO2 (B1) nanobelts. The nano VO2 (B2) is a promising anode material for lithium ion battery application. PMID:27455666

  20. Katzenaugen und Sternsteine: Spielwiese

    NASA Astrophysics Data System (ADS)

    Ucke, Christian; Schlichting, Hans-Joachim

    2004-07-01

    Edelsteine vom Typ Chrysoberyll sind auch unter der Kurzbezeichnung Katzenauge bekannt. Im Chrysoberyll eingelagert sind feine, parallel angeordnete, metallisch glänzende Nadeln aus Rutil (Titandioxid). Auch Hohlkanäle und Risse durchziehen das Material. Lichtreflexion an diesen Einlagerungen und Kanälen erklärt das Lichtband, das dem Stein zu seinem Namen verhalf.

  1. 7 CFR 301.85-2b - Exempted articles. 1

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 5 2013-01-01 2013-01-01 false Exempted articles. 1 301.85-2b Section 301.85-2b... § 301.85-2b Exempted articles. 1 1 The articles hereby exempted remain subject to applicable restrictions under other quarantines and other provisions of this subpart. (a) The following articles...

  2. 7 CFR 301.80-2b - Exempted articles. 1

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 5 2013-01-01 2013-01-01 false Exempted articles. 1 301.80-2b Section 301.80-2b....80-2b Exempted articles. 1 1 The articles hereby exempted remain subject to applicable restrictions under other quarantines. (a) The following articles are exempt from the certification and permit...

  3. 7 CFR 301.85-2b - Exempted articles. 1

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 5 2011-01-01 2011-01-01 false Exempted articles. 1 301.85-2b Section 301.85-2b... § 301.85-2b Exempted articles. 1 1 The articles hereby exempted remain subject to applicable restrictions under other quarantines and other provisions of this subpart. (a) The following articles...

  4. 7 CFR 301.85-2b - Exempted articles. 1

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 5 2010-01-01 2010-01-01 false Exempted articles. 1 301.85-2b Section 301.85-2b... § 301.85-2b Exempted articles. 1 1 The articles hereby exempted remain subject to applicable restrictions under other quarantines and other provisions of this subpart. (a) The following articles...

  5. 7 CFR 301.80-2b - Exempted articles. 1

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 5 2010-01-01 2010-01-01 false Exempted articles. 1 301.80-2b Section 301.80-2b....80-2b Exempted articles. 1 1 The articles hereby exempted remain subject to applicable restrictions under other quarantines. (a) The following articles are exempt from the certification and permit...

  6. PHOX2B is a suppressor of neuroblastoma metastasis

    PubMed Central

    Naftali, Osnat; Maman, Shelly; Meshel, Tsipi; Sagi-Assif, Orit; Ginat, Ravit; Witz, Isaac P.

    2016-01-01

    Paired like homeobox 2B (PHOX2B) is a minimal residual disease (MRD) marker of neuroblastoma. The presence of MRD, also referred to as micro-metastases, is a powerful marker of poor prognosis in neuroblastoma. Lung metastasis is considered a terminal event in neuroblastoma. Lung micro-metastatic neuroblastoma (MicroNB) cells show high expression levels of PHOX2B and possess a less malignant and metastatic phenotype than lung macro metastatic neuroblastoma (MacroNB) cells, which hardly express PHOX2B. In vitro assays showed that PHOX2B knockdown in MicroNB cells did not affect cell viability; however it decreased the migratory capacity of the MicroNB-shPHOX2B cells. An orthotopic inoculation of MicroNB-shPHOX2B cells into the adrenal gland of nude mice resulted in significantly larger primary tumors and a heavier micro-metastatic load in the lungs and bone-marrow, than when control cells were inoculated. PHOX2B expression was found to be regulated by methylation. The PHOX2B promoter in MacroNB cells is significantly more methylated than in MicroNB cells. Demethylation assays using 5-azacytidine demonstrated that methylation can indeed inhibit PHOX2B transcription in MacroNB cells. These pre-clinical data strongly suggest that PHOX2B functions as a suppressor of neuroblastoma progression. PMID:26840262

  7. Falten und fliegen: Papierflieger und ihre Physik

    NASA Astrophysics Data System (ADS)

    Gruber, Werner

    2004-09-01

    Mit Papierfliegern können wichtige Eigenschaften der Aerodynamik anschaulich vermittelt werden: ein Blatt Papier, ein paar Faltungen und schon kann man experimentieren. Allerdings sind beim Trimmen des Fliegers einige Punkte zu beachten. Besonders wichtig ist die Y-Stellung der Flügel, die ihm Flugstabilität verleiht. Ist der Flieger fertig, dann gilt es, die dem Modell am besten angepasste Wurftechnik herauszufinden. Dazu variiert man Wurfgeschwindigkeit und Abwurfwinkel. Den Boden kann ein Papierflieger auf vier prinzipiell verschiedenen Flugkurven erreichen: Optimal ist die Gerade, dann fliegt er am weitesten.

  8. Messung und Analyse

    NASA Astrophysics Data System (ADS)

    Bathelt, Hartmut; Scheinhardt, Michael; Sell, Hendrik; Sottek, Roland; Guidati, Sandro; Helfer, Martin

    Für die Beurteilung von Akustik und Fahrkomfort eines Fahrzeugs gilt in der Fahrzeugentwicklung immer noch der alte Grundsatz: "Der Kunde fährt nicht am Prüfstand, sondern auf der Straße“. Daher werden Gesamtbeurteilungen des Entwicklungsstandes und Konkurrenzvergleiche (Benchmarking) nach wie vor auf der Straße durchgeführt, meist auf ausgewählten Fahrbahnen am Prüfgelände oder im Rahmen der regelmäßigen Winter- und Sommererprobungen unter extremen Witterungsverhältnissen.

  9. MEF2B mutations in non-Hodgkin lymphoma dysregulate cell migration by decreasing MEF2B target gene activation

    PubMed Central

    Pon, Julia R.; Wong, Jackson; Saberi, Saeed; Alder, Olivia; Moksa, Michelle; Grace Cheng, S. -W.; Morin, Gregg B.; Hoodless, Pamela A.; Hirst, Martin; Marra, Marco A.

    2015-01-01

    Myocyte enhancer factor 2B (MEF2B) is a transcription factor with mutation hotspots at K4, Y69 and D83 in diffuse large B-cell lymphoma (DLBCL). To provide insight into the regulatory network of MEF2B, in this study, we analyse global gene expression and DNA-binding patterns. We find that candidate MEF2B direct target genes include RHOB, RHOD, CDH13, ITGA5 and CAV1, and that indirect target genes of MEF2B include MYC, TGFB1, CARD11, MEF2C, NDRG1 and FN1. MEF2B overexpression increases HEK293A cell migration and epithelial–mesenchymal transition, and decreases DLBCL cell chemotaxis. K4E, Y69H and D83V MEF2B mutations decrease the capacity of MEF2B to activate transcription and decrease its' effects on cell migration. The K4E and D83V mutations decrease MEF2B DNA binding. In conclusion, our map of the MEF2B regulome connects MEF2B to drivers of oncogenesis. PMID:26245647

  10. MEF2B mutations in non-Hodgkin lymphoma dysregulate cell migration by decreasing MEF2B target gene activation.

    PubMed

    Pon, Julia R; Wong, Jackson; Saberi, Saeed; Alder, Olivia; Moksa, Michelle; Grace Cheng, S-W; Morin, Gregg B; Hoodless, Pamela A; Hirst, Martin; Marra, Marco A

    2015-01-01

    Myocyte enhancer factor 2B (MEF2B) is a transcription factor with mutation hotspots at K4, Y69 and D83 in diffuse large B-cell lymphoma (DLBCL). To provide insight into the regulatory network of MEF2B, in this study, we analyse global gene expression and DNA-binding patterns. We find that candidate MEF2B direct target genes include RHOB, RHOD, CDH13, ITGA5 and CAV1, and that indirect target genes of MEF2B include MYC, TGFB1, CARD11, MEF2C, NDRG1 and FN1. MEF2B overexpression increases HEK293A cell migration and epithelial-mesenchymal transition, and decreases DLBCL cell chemotaxis. K4E, Y69H and D83V MEF2B mutations decrease the capacity of MEF2B to activate transcription and decrease its' effects on cell migration. The K4E and D83V mutations decrease MEF2B DNA binding. In conclusion, our map of the MEF2B regulome connects MEF2B to drivers of oncogenesis. PMID:26245647

  11. PTK2b function during fertilization of the mouse oocyte

    SciTech Connect

    Luo, Jinping; McGinnis, Lynda K.; Carlton, Carol; Beggs, Hilary E.; Kinsey, William H.

    2014-08-01

    Highlights: • PTK2b is expressed in oocytes and is activated following fertilization. • PTK2b suppression in oocytes prevents fertilization, but not parthenogenetic activation. • PTK2b suppression prevents the oocyte from fusing with or incorporating bound sperm. • PTK2b suppressed oocytes that fail to fertilize do not exhibit calcium oscillations. - Abstract: Fertilization triggers rapid changes in intracellular free calcium that serve to activate multiple signaling events critical to the initiation of successful development. Among the pathways downstream of the fertilization-induced calcium transient is the calcium-calmodulin dependent protein tyrosine kinase PTK2b or PYK2 kinase. PTK2b plays an important role in fertilization of the zebrafish oocyte and the objective of the present study was to establish whether PTK2b also functions in mammalian fertilization. PTK2b was activated during the first few hours after fertilization of the mouse oocyte during the period when anaphase resumption was underway and prior to the pronuclear stage. Suppression of PTK2b kinase activity in oocytes blocked sperm incorporation and egg activation although sperm-oocyte binding was not affected. Oocytes that failed to incorporate sperm after inhibitor treatment showed no evidence of a calcium transient and no evidence of anaphase resumption suggesting that egg activation did not occur. The results indicate that PTK2b functions during the sperm-egg fusion process or during the physical incorporation of sperm into the egg cytoplasm and is therefore critical for successful development.

  12. Getreide, Brot und Feine Backwaren

    NASA Astrophysics Data System (ADS)

    von Grabowski, Hans-Uwe; Rolfe, Birgit

    Getreide und Getreideerzeugnisse sind ebenso wie Brot und Feine Backwaren nach dem Lebensmittel- und Futtermittel-Gesetzbuch (LFGB) [1] Lebensmittel im Sinne des Artikels 2 der VO (EG) Nr. 178/2002 (BasisVO) (s. auch Kap. 1.6/2.4.1/3.2). Gesetzlich festgelegte Begriffsbestimmungen gibt es für diese Lebensmittel nicht. Man muss sich daher allgemeiner Verkehrsauffassungen bedienen, wie sie von der Deutschen Lebensmittelbuch-Kommission in Form von Leitsätzen erarbeitet und veröffentlicht wurden [2]. Der Gesundheitsschutz und der Schutz des Verbrauchers vor Täuschung sind in der Basis-VO und dem LFGB geregelt.

  13. Knockdown of the sodium-dependent phosphate co-transporter 2b (NPT2b) suppresses lung tumorigenesis.

    PubMed

    Hong, Seong-Ho; Minai-Tehrani, Arash; Chang, Seung-Hee; Jiang, Hu-Lin; Lee, Somin; Lee, Ah-Young; Seo, Hwi Won; Chae, Chanhee; Beck, George R; Cho, Myung-Haing

    2013-01-01

    The sodium-dependent phosphate co-transporter 2b (NPT2b) plays an important role in maintaining phosphate homeostasis. In previous studies, we have shown that high dietary inorganic phosphate (Pi) consumption in mice stimulated lung tumorigenesis and increased NPT2b expression. NPT2b has also been found to be highly expressed in human lung cancer tissues. The association of high expression of NPT2b in the lung with poor prognosis in oncogenic lung diseases prompted us to test whether knockdown of NPT2b may regulate lung cancer growth. To address this issue, aerosols that contained small interfering RNA (siRNA) directed against NPT2b (siNPT2b) were delivered into the lungs of K-ras (LA1) mice, which constitute a murine model reflecting human lung cancer. Our results clearly showed that repeated aerosol delivery of siNPT2b successfully suppressed lung cancer growth and decreased cancer cell proliferation and angiogenesis, while facilitating apoptosis. These results strongly suggest that NPT2b plays a role lung tumorigenesis and represents a novel target for lung cancer therapy. PMID:24194864

  14. Unternehmens- und Marktstatistik

    NASA Astrophysics Data System (ADS)

    Grömling, Michael; Scheinost, Ulrich

    Deutschland verfügt über ein gut ausgebautes System amtlicher und nicht amtlicher Unternehmens- und Marktstatistiken, das sich in einem fortwährenden Wandel befindet. Wird es sinnvoll genutzt, können für einzelne Marktteilnehmer wie für die gesamte Gesellschaft kostspielige Fehlentwicklungen vermieden werden. Dazu bedarf es eines sachkundigen Überblicks über die Vielfalt der Statistiken und der zwischen ihnen bestehenden Beziehungen sowie einer ständigen Anpassung an die wirtschaftliche Entwicklung. Als eine mögliche Orientierung kann der auf der Güter- und Faktorebene zu beobachtende Wandel dienen. Einer adäquaten Abbildung der ökonomischen Realität stehen in Deutschland mit seiner starken Verrechtlichung der Statistik jedoch mancherlei Schwierigkeiten im Wege. Teilweise tiefgreifende Reformbestrebungen sind vor allem auf europäischer Ebene im Gange. Als eine ergebnisorientierte Innovation für das Gesamtsystem der Unternehmens- und Marktstatistik wird ein modular aufgebautes System vorgestellt, das auch bei unterschiedlichen und sich wandelnden Rahmenbedingungen schrittweise realisiert werden kann.

  15. Datenintegration und Deduplizierung

    NASA Astrophysics Data System (ADS)

    Bleiholder, Jens; Schmid, Joachim

    In Unternehmen liegen viele Daten heutzutage immer seltener vollständig an einem einzigen physikalischen Ort vor, sondern sind weltweit verteilt. Dies liegt zum einen an der immer besser gewordenen Infrastruktur, die eine solche Verteilung auf einfache Art und Weise ermöglicht, und zum anderen an der Tatsache, dass viele Unternehmen weltweit tätig sind. So fallen Daten weltweit an, werden aber jeweils lokal - vor Ort - gespeichert. Daher müssen oft mehrere Datenquellen genutzt werden, um einen aktuellen, vollständigen und genauen Überblick über die vorhandenen Daten zu gewinnen. Datenintegration hilft, indem sie Daten aus mehreren Quellen zusammenführt und einheitlich darstellt. Diese integrierten Daten können genutzt werden, um sich einen Überblick über das Unternehmen zu verschaffen, z.B. wenn Unternehmen fusionieren und nur noch eine Kundendatenbank bestehen bleiben soll, oder wenn zu einem Kunden die Daten aus den verschiedenen Fachabteilungen zusammengeführt werden sollen. Anhand eines solchen Beispiels, der Integration von Kundendaten zu Kfz- und Lebensversicherungen erläutern wir im Folgenden einzelne Techniken.

  16. Scientific core hole Valles caldera No. 2b (VC-2b), New Mexico

    SciTech Connect

    Garner, J.N.; Hulen, J.B.; Lysne, P.; Jacobson, R.; Goff, F.; Nielson, D.L.; Pisto, L.; Criswell, C.W.; Gribble, R.; Utah Univ. Research Inst., Salt Lake City, UT; Sandia National Labs., Albuquerque, NM; Los Alamos National Lab., NM; Utah Univ. Research Inst., Salt Lake City, UT; Tonto Drilling Services, Inc., Salt Lake City, UT; Los Alamo

    1989-01-01

    Research core hole was continuously cored to 1.762 km on the western flank of the caldera's resurgent dome in 1988. Bottom hole temperature is about 295{degree}C within Precambrian (1.5 Ga) quartz monzonite, deep within the liquid-dominated portions of the Sulphur Springs hydrothermal system. VC-2b may be the deepest, hottest, continuously cored hole in North America. Core recovery was 99.2%. The only major drilling problems encountered were when temperatures at the bit exceeded 225{degree}C below depths of about 1000 m. The result of these conditions was loss of viscosity and/or lubricity in the mud, apparently caused by breakdown of the high temperature polymers. Lithologies in caldera-fill indicate the drill site may be proximal to ignimbrite vents and that an intracaldera lake with temperatures approaching boiling formed soon after the caldera itself. Structural correlations between VC-2b and the 528-m-deep companion hole VC-2a indicate the earlier Toledo caldera (1.45 Ma; Otowi Member tuffs) and even older Lower Tuffs caldera experienced no structural resurgence similar to the 1.12 million year old Valles caldera. The hydrothermal system penetrated by these bores, consists of a shallow vapor-rich cap, which has evolved from an earlier 200{degree}C liquid-dominated system, overlying stacked, liquid-dominated zones up to about 300{degree}C. Geochemistry of mud returns collected during drilling suggests chloride-rich geothermal fluids were entering the bore and mixing with the drilling fluids in the fractured lower Paleozoic and Precambrian sections. 23 refs., 5 figs., 1 tab.

  17. In silico analysis of Brucella abortus Omp2b and in vitro expression of SOmp2b

    PubMed Central

    2016-01-01

    Purpose At present, there is no vaccine available for the prevention of human brucellosis. Brucella outer membrane protein 2b (Omp2b) is a 36 kD porin existed in common Brucella pathogens and it is considered as priority antigen for designing a new subunit vaccine. Materials and Methods In the current study, we aimed to predict and analyze the secondary and tertiary structures of the Brucella abortus Omp2b protein, and to predict T-cell and B-cell epitopes with the help of bioinformatics tools. Subsequently, cloning and expression of the short form of Omp2b (SOmp2b) was performed using pET28a expression vector and Escherichia coli BL21 host, respectively. The recombinant SOmp2b (rSOmp2b) was purified with Ni-NTA column. Results The recombinant protein was successfully expressed in E. coli host and purified under denaturation conditions. The yield of the purified rSOmp2b was estimated by Bradford method and found to be 220 µg/mL of the culture. Conclusion Our results indicate that Omp2b protein has a potential to induce both B-cell– and T-cell–mediated immune responses and it can be evaluated as a new subunit vaccine candidate against brucellosis. PMID:26866027

  18. Geologie der terrestrischen Planeten und Monde.

    NASA Astrophysics Data System (ADS)

    Stöffler, D.

    Contents: 1. Inhalt und Aufgabe der Planetologie. 2. Aufbau des Sonnensystems. 3. Methoden der Exploration und Analyse der Planeten und Monde. 4. Geologische Grundprozesse auf den terrestrischen Planeten und Monden. 5. Geologische Formationen der planetaren Oberflächen. 6. Gesteine und Mineralien der planetaren Krusten. 7. Der innere Aufbau der terrestrischen planetaren Körper. 8. Vergleichende geologische Entwicklungsgeschichte der terrestrischen Planeten und des Mondes. 9. Ursprung und Entstehung der terrestrischen planetaren Körper.

  19. Building Customized University-to-Business (U2B) Partnerships

    ERIC Educational Resources Information Center

    Irvine, George; Verma, Lisa

    2013-01-01

    Continuing education (CE) units throughout the United States have successfully built University-to-Business (U2B) partnerships to provide greater value to their community partners and to increase revenue for the university. Our experience in building U2B partnerships and feedback from our partners--businesses, corporations, state agencies, and…

  20. Role of adenosine A2B receptors in inflammation

    PubMed Central

    Feoktistov, Igor; Biaggioni, Italo

    2013-01-01

    Recent progress in our understanding of the unique role of A2B receptors in the regulation of inflammation, immunity and tissue repair was considerably facilitated with the introduction of new pharmacological and genetic tools. However, it also led to seemingly conflicting conclusions on the role of A2B adenosine receptors in inflammation with some publications indicating pro-inflammatory effects and others suggesting the opposite. This chapter reviews the functions of A2B receptors in various cell types related to inflammation and integrated effects of A2B receptor modulation in several animal models of inflammation. It is argued that translation of current findings into novel therapies would require a better understanding of A2B receptors functions in diverse types of inflammatory responses in various tissues and at different points of their progression. PMID:21586358

  1. Patentierung und Patentlage

    NASA Astrophysics Data System (ADS)

    Herrmann, Uwe

    Gewerbliche Schutzrechte nehmen in der nationalen Rechts- und Wirtschaftsordnung sowie auch auf internationaler Ebene stetig an Bedeutung zu. Sie dienen dem Schutz geistigen Eigentums und sind für jeden Gewerbetreibenden nicht nur im Hinblick darauf von Bedeutung, eigene Rechte zu sichern, sondern auch insofern von Relevanz, dass ein Verstoß gegen Rechte Dritter zu vermeiden ist. Zu den gewerblichen Schutzrechten gehören unter anderem Kennzeichenrechte, Geschmacksmusterrechte sowie die sogenannten technischen Schutzrechte in Form des Patents sowie des Gebrauchsmusters. Die folgenden Ausführungen befassen sich ausschließlich mit den technischen Schutzrechten und geben eine kurze Einführung in die Voraussetzungen, das Entstehen und den Wegfall sowie in die Wirkungen technischer Schutzrechte. Beleuchtet wird die Situation im Wesentlichen im Hinblick auf nationale technische Schutzrechte, d. h. auf Deutsche Patente und Gebrauchsmuster sowie auf Europäische Patente, die Schutz in Deutschland entfalten. Die Möglichkeit der Erlangung von Schutzrechten im außereuropäischen Ausland wird nur am Rande gestreift.

  2. Technikwissenschaft - Erfinden und Entdecken

    NASA Astrophysics Data System (ADS)

    Linnemann, Gerhard

    Umrissen wird das allgemeine Ziel der Technikwissenschaft, konstruktiv zu verwerten und nicht-natürlich Entdeckbares zu erfinden. Wir befinden uns in einer Umwälzung der Technik im Verlauf der wissenschaftlich-technischen Revolution, auf dem Wege zu einem neuen Techniktyp. Dieser schafft und nutzt die künstliche Intelligenz. Dazu benötigt der in der Technik tätige Mensch spezielle Kenntnisse und Erfahrungen in kreativ-konstruktiver, -gestalterischer und erfinderischer Sicht mit dem Einsatz spezieller Strukturen und Sprachen. Vorschläge zur Arbeitsweise in der Technik werden gegeben.Translated AbstractTechnological Science-Invent and DiscoverThe general aim of engineering science is outlined to utilize results constructively and to invent something that cannot be discovered in nature. We are now in a period of transformation of technology in the course of scientific-technological revolution, on the way to a new type of technology. This new type creates and utilizes artificial intelligence. For this, man acitive in this field requires special knowledge and experiences in a creative, constructive, design-oriented and ultimately inventive way by deploying special structures and languages. There are also made some proposals concerning the method of working in the field of technology.

  3. Chromatin-to-nucleoprotamine transition is controlled by the histone H2B variant TH2B

    PubMed Central

    Montellier, Emilie; Boussouar, Fayçal; Rousseaux, Sophie; Zhang, Kai; Buchou, Thierry; Fenaille, François; Shiota, Hitoshi; Debernardi, Alexandra; Héry, Patrick; Curtet, Sandrine; Jamshidikia, Mahya; Barral, Sophie; Holota, Hélène; Bergon, Aurélie; Lopez, Fabrice; Guardiola, Philippe; Pernet, Karin; Imbert, Jean; Petosa, Carlo; Tan, Minjia; Zhao, Yingming; Gérard, Matthieu; Khochbin, Saadi

    2013-01-01

    The conversion of male germ cell chromatin to a nucleoprotamine structure is fundamental to the life cycle, yet the underlying molecular details remain obscure. Here we show that an essential step is the genome-wide incorporation of TH2B, a histone H2B variant of hitherto unknown function. Using mouse models in which TH2B is depleted or C-terminally modified, we show that TH2B directs the final transformation of dissociating nucleosomes into protamine-packed structures. Depletion of TH2B induces compensatory mechanisms that permit histone removal by up-regulating H2B and programming nucleosome instability through targeted histone modifications, including lysine crotonylation and arginine methylation. Furthermore, after fertilization, TH2B reassembles onto the male genome during protamine-to-histone exchange. Thus, TH2B is a unique histone variant that plays a key role in the histone-to-protamine packing of the male genome and guides genome-wide chromatin transitions that both precede and follow transmission of the male genome to the egg. PMID:23884607

  4. Recent developments in A2B adenosine receptor ligands.

    PubMed

    Kalla, Rao V; Zablocki, Jeff; Tabrizi, Mojgan Aghazadeh; Baraldi, Pier Giovanni

    2009-01-01

    A selective, high-affinity A(2B) adenosine receptor (AR) antagonist will be useful as a pharmacological tool to help determine the role of the A(2B)AR in inflammatory diseases and angiogenic diseases. Based on early A(2B)AR-selective ligands with nonoptimal pharmaceutical properties, such as 15 (MRS 1754: K(i)(hA(2B)) = 2 nM; K(i)(hA(1)) = 403 nM; K(i)(hA(2A)) = 503 NM, and K(i)(hA(3)) = 570 nM), several groups have discovered second-generation A(2B)AR ligands that are suitable for development. Scientists at CV Therapeutics have discovered the selective, high-affinity A(2B)AR antagonist 22, a 8-(4-pyrazolyl)-xanthine derivative, (CVT-6883, K(i)(hA(2B)) = 22 nM; K(i)(hA(1)) = 1,940 nM; K(i)(hA(2A)) = 3,280; and K(i)(hA(3)) = 1,070 nM). Compound 22 has demonstrated favorable pharmacokinetic (PK) properties (T(1/2) = 4 h and F > 35% rat), and it is a functional antagonist at the A(2B)AR(K (B) = 6 nM). In a mouse model of asthma, compound 22 demonstrated a dose-dependent efficacy supporting the role of the A(2B)AR in asthma. In two Phase I clinical trails, 22 (CVT-6883) was found to be safe, well tolerated, and suitable for once-daily dosing. Baraldi et al. have independently discovered a selective, high-affinity A(2B)AR antagonist, 30 (MRE2029F20), 8-(5-pyrazolyl)-xanthine (K(i)(hA(2B)) = 5.5 nM; K(i)(hA(1)) = 200 nM; K(i)(hA(2A), A(3)) > 1,000, that has been selected for development in conjunction with King Pharmaceuticals. Compound 30 has been demonstrated to be a functional antagonist of the A(2B)AR, and it has been radiolabeled for use in pharmacological studies. A third compound, 58 (LAS-38096), is a 2-aminopyrimidine derivative (discovered by the Almirall group) that has high A(2B)AR affinity and selectivity (K(i)(hA(2B)) = 17 nM; K(i)(hA(1)) > 1,000 nM; K(i)(hA(2A)) > 2,500; and K(i)(hA(3)) > 1,000 nM), and 58 has been moved into preclinical safety testing. A fourth selective, high-affinity A(2B)AR antagonist, 54 (OSIP339391 K(i))(hA(2B)) = 0.5 nM; K(i))(hA(1

  5. Venture Kapital und Life Science

    NASA Astrophysics Data System (ADS)

    Moss, Sebastian; Beermann, Christian

    Um sich weiter im internationalen Wettbewerb behaupten zu können, müssen deutsche Unternehmen heute in Schlüsseltechnologien wie die Medizintechnik und die Biotechnologie, zusammenfassend unter dem Begriff der Life Sciences bekannt, investieren. Eine führende Wettbewerbsposition erfordert immer die konsequente Weiterentwicklung von Produkten und Lösungen, um Innovationspotenziale in medizinische Verfahren umzusetzen. Die damit unmittelbar verbundenen hohen Ausgaben für Forschung und Entwicklung stellen ein bedeutendes Problem junger Life Science Unternehmen dar. Vor allem die, verglichen mit nicht-medizinischen Branchen, längeren Forschungs- und Entwicklungszyklen in der Frühphase eines Life Science Unternehmens und die längere Dauer bis zur Profitabilität erhöhen das Risiko der Finanzinvestoren. Die Zeitdauer, um ein medizinisches Produkt bis zur Marktreife zu entwickeln und letztlich auf dem Markt anzubieten, kann aufgrund der notwendigen intensiven Forschung nur unscharf geplant werden und erhöht die Unsicherheit über den Zeitpunkt der ersten Einnahmen. Damit verschärfen sich gerade im Life Science Bereich allgemeine Problematiken von Gründungs- und Wachstumsfinanzierungen wie starke Informationsasymmetrien zwischen Gründer und potentiellen Kapitalgebern. Oftmals ist die Entwicklung einer innovativen Technologie abhängig von einzelnen Personen, von deren Wissen und Engagement die Umsetzung und der Erfolg eines gesamten Produktkonzeptes abhängen.

  6. Rf2a and rf2b transcription factors

    DOEpatents

    Beachy, Roger N.; Petruccelli, Silvana; Dai, Shunhong

    2007-10-02

    A method of activating the rice tungro bacilliform virus (RTBV) promoter in vivo is disclosed. The RTBV promoter is activated by exposure to at least one protein selected from the group consisting of Rf2a and Rf2b.

  7. Crystal structure of eukaryotic translation initiation factor 2B.

    PubMed

    Kashiwagi, Kazuhiro; Takahashi, Mari; Nishimoto, Madoka; Hiyama, Takuya B; Higo, Toshiaki; Umehara, Takashi; Sakamoto, Kensaku; Ito, Takuhiro; Yokoyama, Shigeyuki

    2016-03-01

    Eukaryotic cells restrict protein synthesis under various stress conditions, by inhibiting the eukaryotic translation initiation factor 2B (eIF2B). eIF2B is the guanine nucleotide exchange factor for eIF2, a heterotrimeric G protein consisting of α-, β- and γ-subunits. eIF2B exchanges GDP for GTP on the γ-subunit of eIF2 (eIF2γ), and is inhibited by stress-induced phosphorylation of eIF2α. eIF2B is a heterodecameric complex of two copies each of the α-, β-, γ-, δ- and ε-subunits; its α-, β- and δ-subunits constitute the regulatory subcomplex, while the γ- and ε-subunits form the catalytic subcomplex. The three-dimensional structure of the entire eIF2B complex has not been determined. Here we present the crystal structure of Schizosaccharomyces pombe eIF2B with an unprecedented subunit arrangement, in which the α2β2δ2 hexameric regulatory subcomplex binds two γε dimeric catalytic subcomplexes on its opposite sides. A structure-based in vitro analysis by a surface-scanning site-directed photo-cross-linking method identified the eIF2α-binding and eIF2γ-binding interfaces, located far apart on the regulatory and catalytic subcomplexes, respectively. The eIF2γ-binding interface is located close to the conserved 'NF motif', which is important for nucleotide exchange. A structural model was constructed for the complex of eIF2B with phosphorylated eIF2α, which binds to eIF2B more strongly than the unphosphorylated form. These results indicate that the eIF2α phosphorylation generates the 'nonproductive' eIF2-eIF2B complex, which prevents nucleotide exchange on eIF2γ, and thus provide a structural framework for the eIF2B-mediated mechanism of stress-induced translational control. PMID:26901872

  8. 27 CFR 21.33 - Formula No. 2-B.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Formula No. 2-B. 21.33 Section 21.33 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY LIQUORS FORMULAS FOR DENATURED ALCOHOL AND RUM Specially Denatured Spirits Formulas and Authorized Uses § 21.33 Formula No. 2-B....

  9. 27 CFR 21.33 - Formula No. 2-B.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2013-04-01 2013-04-01 false Formula No. 2-B. 21.33 Section 21.33 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY ALCOHOL FORMULAS FOR DENATURED ALCOHOL AND RUM Specially Denatured Spirits Formulas and Authorized Uses § 21.33 Formula No. 2-B....

  10. 27 CFR 21.33 - Formula No. 2-B.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2011-04-01 2011-04-01 false Formula No. 2-B. 21.33 Section 21.33 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY LIQUORS FORMULAS FOR DENATURED ALCOHOL AND RUM Specially Denatured Spirits Formulas and Authorized Uses § 21.33 Formula No. 2-B....

  11. Npt2b Deletion Attenuates Hyperphosphatemia Associated with CKD

    PubMed Central

    Tang, Wen; Bracken, Christina; O’Brien, Stephen P.; Song, Wenping; Boulanger, Joseph; Ryan, Susan; Phillips, Lucy; Liu, Shiguang; Arbeeny, Cynthia; Ledbetter, Steven; Sabbagh, Yves

    2012-01-01

    The incidence of cardiovascular events and mortality strongly correlates with serum phosphate in individuals with CKD. The Npt2b transporter contributes to maintaining phosphate homeostasis in the setting of normal renal function, but its role in CKD-associated hyperphosphatemia is not well understood. Here, we used adenine to induce uremia in both Npt2b-deficient and wild-type mice. Compared with wild-type uremic mice, Npt2b-deficient uremic mice had significantly lower levels of serum phosphate and attenuation of FGF23. Treating Npt2b-deficient mice with the phosphate binder sevelamer carbonate further reduced serum phosphate levels. Uremic mice exhibited high turnover renal osteodystrophy; treatment with sevelamer significantly decreased the number of osteoclasts and the rate of mineral apposition in Npt2b-deficient mice, but sevelamer did not affect bone formation and rate of mineral apposition in wild-type mice. Taken together, these data suggest that targeting Npt2b in addition to using dietary phosphorus binders may be a therapeutic approach to modulate serum phosphate in CKD. PMID:22859851

  12. Kometen und Asteroiden

    NASA Astrophysics Data System (ADS)

    Borgeest, Ulf; Staude, Jakob; Hahn, Gerhard; Harris, Alan W.; Jaumann, Ralf; Köhler, Ulrich; Kührt, Ekkehard; Schulz, Rita; Neukum, Gerhard; Arnold, Gabriele; Keller, Horst Uwe; Denk, Tilmann; Müller, Thomas; Wulff, André; Maruhn, Nicolaus; Fischer, Daniel; Trieloff, Mario; Althaus, Tilmann

    Contents: Die Kleinkörper des Sonnensystems. Kern, Koma und Schweife. Ziele der Planetenforschung. ROSETTA: Naherkundung von Kometen. Asteroiden: Trümmer aus planetarer Urzeit. Kleinkörper im Infrarotweltall. Selbs beobachten! Apocalypse - not now! Meteoriten - Boten aus der Urzeit des Sonnensystems.

  13. Tipps und Tricks

    NASA Astrophysics Data System (ADS)

    Häger, Wolfgang; Bauermeister, Dirk

    Hier wollen wir einige uns nützlich erscheinende Hinweise zur Arbeit mit dem Inventor geben. Dabei geht es vor allem darum, das Arbeiten mit dem Inventor zu vereinfachen. Die Beispiele stellen eine unvollständige Aufzählung dar und sollen dazu anregen, nach alternativen Vorgehensweisen zu suchen (hier sei noch einmal ausdrücklich auf das Internet verwiesen).

  14. Arbeitsgestaltung und Mitarbeiterqualifizierung

    NASA Astrophysics Data System (ADS)

    Weiss-Oberdorfer, Werner; Hörner, Barbara; Holm, Ruth; Pirner, Evelin

    Die Wertkette gliedert ein Unternehmen in strategisch relevante Tätigkeiten, um dadurch Kostenverhalten sowie vorhandene und potenzielle Differenzierungsquellen zu verstehen. Wenn ein Unternehmen diese strategisch wichtigen Aktivitäten billiger oder besser als seine Konkurrenten erledigt, verschafft es sich einen Wettbewerbsvorteil." Michael Porter, 1985

  15. Pharmacogenetics of cytochrome P450 2B6 (CYP2B6): advances on polymorphisms, mechanisms, and clinical relevance

    PubMed Central

    Zanger, Ulrich M.; Klein, Kathrin

    2013-01-01

    Cytochrome P450 2B6 (CYP2B6) belongs to the minor drug metabolizing P450s in human liver. Expression is highly variable both between individuals and within individuals, owing to non-genetic factors, genetic polymorphisms, inducibility, and irreversible inhibition by many compounds. Drugs metabolized mainly by CYP2B6 include artemisinin, bupropion, cyclophosphamide, efavirenz, ketamine, and methadone. CYP2B6 is one of the most polymorphic CYP genes in humans and variants have been shown to affect transcriptional regulation, splicing, mRNA and protein expression, and catalytic activity. Some variants appear to affect several functional levels simultaneously, thus, combined in haplotypes, leading to complex interactions between substrate-dependent and -independent mechanisms. The most common functionally deficient allele is CYP2B6*6 [Q172H, K262R], which occurs at frequencies of 15 to over 60% in different populations. The allele leads to lower expression in liver due to erroneous splicing. Recent investigations suggest that the amino acid changes contribute complex substrate-dependent effects at the activity level, although data from recombinant systems used by different researchers are not well in agreement with each other. Another important variant, CYP2B6*18 [I328T], occurs predominantly in Africans (4–12%) and does not express functional protein. A large number of uncharacterized variants are currently emerging from different ethnicities in the course of the 1000 Genomes Project. The CYP2B6 polymorphism is clinically relevant for HIV-infected patients treated with the reverse transcriptase inhibitor efavirenz, but it is increasingly being recognized for other drug substrates. This review summarizes recent advances on the functional and clinical significance of CYP2B6 and its genetic polymorphism, with particular emphasis on the comparison of kinetic data obtained with different substrates for variants expressed in different recombinant expression systems. PMID

  16. Antagonistic effects of extracts from Artemisia rupetris L. and Leontopodium leontopodioides to CC chemokine receptor 2b (CCR2b).

    PubMed

    Yu, Qin-Wei; Hu, Jie; Wang, Hao; Chen, Xin; Zhao, Fang; Gao, Peng; Yang, Qiu-Bin; Sun, Dan-Dan; Zhang, Lu-Yong; Yan, Ming

    2016-05-01

    The present study was designed to establish a suitable assay to explore CCR2b receptor antagonists from the natural products of Artemisia rupetris and Leontopodium leontopodioides. An aequorin assay was developed as a cell-based assay suitable for 384-well microplate and used for screening CCR2b receptor antagonists from natural products. Through establishing suitable conditions, the assay was shown to be suitable for screening of CCR2b receptor antagonists. Seven compounds were identified in preliminary screening. Five of them showed evident dose-response relationship in secondary screening. The structure-activity relationship study suggested that 7-position hydroxyl group of flavonoids was necessary, a polar group should be introduced on the 3-position, and the substituents on 2-position benzene ring of flavonoids have little influence on the potentency of the inhibition activity on CCR2b receptor. The ortho-position dihydroxyl structure in quinic acid compounds may be important. In conclusion, Compounds HR-1, 5, 7, and AR-20, 35 showed activity as antagonist of CCR2b receptor, which shed lights on the development of novel drugs as CCR2b receptor antagonists for preventing inflammation related diseases. PMID:27478099

  17. Fibrillin-2b regulates endocardial morphogenesis in zebrafish.

    PubMed

    Mellman, Katharine; Huisken, Jan; Dinsmore, Colin; Hoppe, Cornelia; Stainier, Didier Y

    2012-12-01

    scotch tape (sco) is a zebrafish cardiac mutant initially proposed to exhibit a reduced amount of cardiac jelly, the extracellular matrix between the myocardial and endocardial layers. We analyzed sco(te382) mutant hearts in detail using both selective plane illumination microscopy (SPIM) and transmission electron microscopy (TEM), and observed a fascinating endocardial defect. Time-lapse SPIM imaging of wild-type and mutant embryos revealed significant and dynamic gaps between endocardial cells during development. Although these gaps close in wild-type animals, they fail to close in the mutants, ultimately leading to a near complete absence of endocardial cells in the atrial chamber by the heart looping stage. TEM analyses confirm the presence of gaps between endocardial cells in sco mutants, allowing the apparent leakage of cardiac jelly into the lumen. High-resolution mapping places the sco(te382) mutation within the fbn2b locus, which encodes the extracellular matrix protein Fibrillin 2b (OMIM ID: 121050). Complementation and further phenotypic analyses confirm that sco is allelic to puff daddy(gw1) (pfd(gw1)), a null mutant in fbn2b, and that sco(te382) is a hypomorphic allele of fbn2b. fbn2b belongs to a family of genes responsible for the assembly of microfibrils throughout development, and is essential for microfibril structural integrity. In sco(te382) mutants, Fbn2b is disabled by a missense mutation in a highly conserved cbEGF domain, which likely interferes with protein folding. Integrating data obtained from microscopy and molecular biology, we posit that this mutation impacts the rigidity of Fbn2b, imparting a structural defect that weakens endocardial adhesion thereby resulting in perforated endocardium. PMID:22841646

  18. Serotonin 2B Receptor Antagonism Prevents Heritable Pulmonary Arterial Hypertension

    PubMed Central

    Schroer, Alison K.; Chen, Peter; Ryzhova, Larisa M.; Gladson, Santhi; Shay, Sheila; Hutcheson, Joshua D.; Merryman, W. David

    2016-01-01

    Serotonergic anorexigens are the primary pharmacologic risk factor associated with pulmonary arterial hypertension (PAH), and the resulting PAH is clinically indistinguishable from the heritable form of disease, associated with BMPR2 mutations. Both BMPR2 mutation and agonists to the serotonin receptor HTR2B have been shown to cause activation of SRC tyrosine kinase; conversely, antagonists to HTR2B inhibit SRC trafficking and downstream function. To test the hypothesis that a HTR2B antagonist can prevent BMRP2 mutation induced PAH by restricting aberrant SRC trafficking and downstream activity, we exposed BMPR2 mutant mice, which spontaneously develop PAH, to a HTR2B antagonist, SB204741, to block the SRC activation caused by BMPR2 mutation. SB204741 prevented the development of PAH in BMPR2 mutant mice, reduced recruitment of inflammatory cells to their lungs, and reduced muscularization of their blood vessels. By atomic force microscopy, we determined that BMPR2 mutant mice normally had a doubling of vessel stiffness, which was substantially normalized by HTR2B inhibition. SB204741 reduced SRC phosphorylation and downstream activity in BMPR2 mutant mice. Gene expression arrays indicate that the primary changes were in cytoskeletal and muscle contractility genes. These results were confirmed by gel contraction assays showing that HTR2B inhibition nearly normalizes the 400% increase in gel contraction normally seen in BMPR2 mutant smooth muscle cells. Heritable PAH results from increased SRC activation, cellular contraction, and vascular resistance, but antagonism of HTR2B prevents SRC phosphorylation, downstream activity, and PAH in BMPR2 mutant mice. PMID:26863209

  19. Lithium insertion in nanostructured TiO(2)(B) architectures.

    PubMed

    Dylla, Anthony G; Henkelman, Graeme; Stevenson, Keith J

    2013-05-21

    Electric vehicles and grid storage devices have potentialto become feasible alternatives to current technology, but only if scientists can develop energy storage materials that offer high capacity and high rate capabilities. Chemists have studied anatase, rutile, brookite and TiO2(B) (bronze) in both bulk and nanostructured forms as potential Li-ion battery anodes. In most cases, the specific capacity and rate of lithiation and delithiation increases as the materials are nanostructured. Scientists have explained these enhancements in terms of higher surface areas, shorter Li(+) diffusion paths and different surface energies for nanostructured materials allowing for more facile lithiation and delithiation. Of the most studied polymorphs, nanostructured TiO2(B) has the highest capacity with promising high rate capabilities. TiO2(B) is able to accommodate 1 Li(+) per Ti, giving a capacity of 335 mAh/g for nanotubular and nanoparticulate TiO2(B). The TiO2(B) polymorph, discovered in 1980 by Marchand and co-workers, has been the focus of many recent studies regarding high power and high capacity anode materials with potential applications for electric vehicles and grid storage. This is due to the material's stability over multiple cycles, safer lithiation potential relative to graphite, reasonable capacity, high rate capability, nontoxicity, and low cost (Bruce, P. G.; Scrosati, B.; Tarascon, J.-M. Nanomaterials for Rechargeable Lithium Batteries. Angew. Chem., Int. Ed.2008, 47, 2930-2946). One of the most interesting properties of TiO2(B) is that both bulk and nanostructured forms lithiate and delithiate through a surface redox or pseudocapacitive charging mechanism, giving rise to stable high rate charge/discharge capabilities in the case of nanostructured TiO2(B). When other polymorphs of TiO2 are nanostructured, they still mainly intercalate lithium through a bulk diffusion-controlled mechanism. TiO2(B) has a unique open crystal structure and low energy Li

  20. Rap2B GTPase: structure, functions, and regulation.

    PubMed

    Zhu, Zhesi; Di, Jiehui; Lu, Zheng; Gao, Keyu; Zheng, Junnian

    2016-06-01

    Rap2B GTPase, a member of Ras-related protein superfamily, was first discovered from a platelet cDNA library in the early 1990s. Since then, it has been reported to play an important role in regulating cellular processes including cytoskeletal organization, cell growth, and proliferation. It can be stimulated and suppressed by a wide range of external and internal inducers, circulating between GTP-bound active state and GDP-bound inactive state. Increasing focus on Ras signaling pathway reveals critical effects of Rap2B on tumorigenesis. In particular, Rap2B behaves in a p53-dependent manner in regulation of apoptosis and migration. Apart from being an oncogenic activator, Rap2B has been found to participate in many other physiological events via diverse downstream effectors. In this review, we present recent studies on the structure, regulation, and multiple biological functions of Rap2B, shedding light on its potential status in treatment of cancer as well as other diseases. PMID:27012552

  1. Wirkstoffe, Medikamente und Mathematische Bildverarbeitung

    NASA Astrophysics Data System (ADS)

    Bauer, Günter J.; Lorenz, Dirk A.; Maaß, Peter; Preckel, Hartwig; Trede, Dennis

    Die Entwicklung neuer Medikamente ist langwierig und teuer. Der erste Schritt ist hierbei die Suche nach neuen Wirkstoffkandidaten, die für die Behandlung bislang schwer therapierbarer Krankheiten geeignet sind. Hierfür stehen der Pharma- und Biotechnologieindustrie riesige Substanzbibliotheken zur Verfügung. In diesen Bibliotheken werden die unterschiedlichsten Substanzen gesammelt, die entweder synthetisch hergestellt oder aus Pilzen, Bakterienkulturen und anderen Lebewesen gewonnen werden können.

  2. Substrate Recognition of Histone H2B by DUBm

    NASA Astrophysics Data System (ADS)

    Henderson, Elizabeth; Berndsen, Christopher; Wolberger, Cynthia

    2011-03-01

    The SAGA complex is a transcriptional coactivator that regulates gene expression in eukaryotes via histone acetylation and deubiquitination, which are crucial for transcription. Our lab is investigating the SAGA-dependent deubiquitination of histone H2B. The deubiquitinating module (DUBm) of SAGA is comprised of a ubiquitin-specific protease, Ubp8, and three other proteins. It is known that Ubp8 cleaves ubiquitin from histone H2B, however, the specific way in which the enzyme binds to the substrate remains elusive. In order to unravel this mechanism, we attempted to determine the crystal structure of the substrate binding complex. We obtained this substrate by exploiting the techniques of intein chemistry to artificially ubiquitinate a histone H2B peptide, which we then co-crystallized with DUBm. Additionally, we synthesized Ub-K63R-linked chains and Ub-K48-linked chains and co-crystallized them with DUBm.

  3. Expanding Interprofessional EHR Data in i2b2.

    PubMed

    Westra, Bonnie L; Christie, Beverly; Johnson, Steven G; Pruinelli, Lisiane; LaFlamme, Anne; Park, Jung In; Sherman, Suzan G; Byrne, Matthew D; Ranallo, Piper; Speedie, Stuart

    2016-01-01

    Emerging issues of team-based care, precision medicine, and big data science underscore the need for health information technology (HIT) tools for integrating complex data in consistent ways to achieve the triple aims of improving patient outcomes, patient experience, and cost reductions. The purpose of this study was to demonstrate the feasibility of creating a hierarchical flowsheet ontology in i2b2 using data-derived information models and determine the underlying informatics and technical issues. This study is the first of its kind to use information models that aggregate team-based care across time, disciplines, and settings into 14 information models that were integrated into i2b2 in a hierarchical model. In the process of successfully creating a hierarchical ontology for flowsheet data in i2b2, we uncovered a variety of informatics and technical issues described in this paper. PMID:27570680

  4. Expanding Interprofessional EHR Data in i2b2

    PubMed Central

    Westra, Bonnie L.; Christie, Beverly; Johnson, Steven G.; Pruinelli, Lisiane; LaFlamme, Anne; Park, Jung In; Sherman, Suzan G.; Byrne, Matthew D.; Ranallo, Piper; Speedie, Stuart

    2016-01-01

    Emerging issues of team-based care, precision medicine, and big data science underscore the need for health information technology (HIT) tools for integrating complex data in consistent ways to achieve the triple aims of improving patient outcomes, patient experience, and cost reductions. The purpose of this study was to demonstrate the feasibility of creating a hierarchical flowsheet ontology in i2b2 using data-derived information models and determine the underlying informatics and technical issues. This study is the first of its kind to use information models that aggregate team-based care across time, disciplines, and settings into 14 information models that were integrated into i2b2 in a hierarchical model. In the process of successfully creating a hierarchical ontology for flowsheet data in i2b2, we uncovered a variety of informatics and technical issues described in this paper. PMID:27570680

  5. caB2B hosting update —

    Cancer.gov

    cancer Bench-to-Beside - caB2B - is an open-source query tool that permits translational research scientists to search and combine data from virtually any caGrid data service. The caB2B suite is composed of three core components: the Web application, the Client Application and the Administrative Module. The caB2B Web Application provides query templates that allow easy search and retrieval of microarray data (from caArray), imaging data (from the National Biomedical Imaging Archive (NBIA)), specimen data (from caTissue) and nanoparticle data (from caNanoLab) across the grid. Searches can be performed on selected locations using either form-based or keyword searches and data can be exported in the CSV format.

  6. Multiple endocrine neoplasia type 2b associated with lichen nitidus.

    PubMed

    Altaykan, Asli; Ersoy-Evans, Sibel; Emre, Serap; Orhan, Diclehan; Güçer, Safak; Erkin, Gül

    2007-01-01

    Multiple endocrine neoplasia (MEN) type 2B syndrome is an autosomal dominantly inherited endocrine disorder with rare skin manifestations. We report the case of a 19-year-old Turkish girl who presented with skin-colored flat papules scattered all over the trunk and extremities. Additionally, she had marfanoid habitus, thick lips, and multiple flesh-colored papules over the inner eyelids and oral mucosa. Histopathological examination of one of the trunk lesions was consistent with lichen nitidus. Her past medical history was significant for medullary thyroid carcinoma. Genetic testing showed a point mutation in exon 16 at codon 918 (M918T) in the RET proto-oncogene. Based on all these findings, MEN type 2B was diagnosed. To the best of our knowledge we report the first case of MEN type 2B associated with lichen nitidus. PMID:17540634

  7. ORM-Based Semantics of B2B Transactions

    NASA Astrophysics Data System (ADS)

    Balsters, H.; van Blommestein, F.

    After widespread implementation of Enterprise Resource Planning and Personal Information Management, the next wave in the application of ICT is headed towards business to business (B2B) communication. B2B has a number of specific aspects, one of them being negotiation. This aspect has been largely neglected by present implementations of standard EDI- or XML-messaging and by B2B webservice implementations. In this paper a precise model is given of the negotiation process. The requirements of a potential Buyer and the offer of a potential Seller are matched and, if the negotiation is successful, a contract is concluded. The negotiation process model is represented in ORM, extended with dynamic constraints. Our model may be implemented in the databases of the trading partners and in message- or service definitions.

  8. Flow Simulation of N2B Hybrid Wing Body Configuration

    NASA Technical Reports Server (NTRS)

    Kim, Hyoungjin; Liou, Meng-Sing

    2012-01-01

    The N2B hybrid wing body aircraft was conceptually designed to meet environmental and performance goals for the N+2 generation transport set by the subsonic fixed wing project. In this study, flow fields around the N2B configuration is simulated using a Reynolds-averaged Navier-Stokes flow solver using unstructured meshes. Boundary conditions at engine fan face and nozzle exhaust planes are provided by response surfaces of the NPSS thermodynamic engine cycle model. The present flow simulations reveal challenging design issues arising from boundary layer ingestion offset inlet and nacelle-airframe interference. The N2B configuration can be a good test bed for application of multidisciplinary design optimization technology.

  9. 27 CFR 21.33 - Formula No. 2-B.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2014-04-01 2014-04-01 false Formula No. 2-B. 21.33 Section 21.33 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY ALCOHOL FORMULAS FOR DENATURED ALCOHOL AND RUM Specially Denatured Spirits...

  10. INSAT-2A and 2B development mechanisms

    NASA Technical Reports Server (NTRS)

    Sathyanarayan, M. N.; Rao, M. Nageswara; Nataraju, B. S.; Viswanatha, N.; Chary, M. Laxmana; Balan, K. S.; Murthy, V. Sridhara; Aller, Raju; Kumar, H. N. Suresha

    1994-01-01

    The Indian National Satellite (INSAT) 2A and 2B have deployment mechanisms for deploying the solar array, two C/S band antenna reflectors and a coilable lattice boom with sail. The mechanisms have worked flawlessly on both satellites. The configuration details, precautions taken during the design phase, the test philosophy, and some of the critical analysis activities are discussed.

  11. Strategies for maintaining patient privacy in i2b2

    PubMed Central

    Gainer, Vivian; Mendis, Michael; Churchill, Susanne; Kohane, Isaac

    2011-01-01

    Background The re-use of patient data from electronic healthcare record systems can provide tremendous benefits for clinical research, but measures to protect patient privacy while utilizing these records have many challenges. Some of these challenges arise from a misperception that the problem should be solved technically when actually the problem needs a holistic solution. Objective The authors' experience with informatics for integrating biology and the bedside (i2b2) use cases indicates that the privacy of the patient should be considered on three fronts: technical de-identification of the data, trust in the researcher and the research, and the security of the underlying technical platforms. Methods The security structure of i2b2 is implemented based on consideration of all three fronts. It has been supported with several use cases across the USA, resulting in five privacy categories of users that serve to protect the data while supporting the use cases. Results The i2b2 architecture is designed to provide consistency and faithfully implement these user privacy categories. These privacy categories help reflect the policy of both the Health Insurance Portability and Accountability Act and the provisions of the National Research Act of 1974, as embodied by current institutional review boards. Conclusion By implementing a holistic approach to patient privacy solutions, i2b2 is able to help close the gap between principle and practice. PMID:21984588

  12. GRIN2B predicts attention problems among disadvantaged children.

    PubMed

    Riva, Valentina; Battaglia, Marco; Nobile, Maria; Cattaneo, Francesca; Lazazzera, Claudio; Mascheretti, Sara; Giorda, Roberto; Mérette, Chantal; Émond, Claudia; Maziade, Michel; Marino, Cecilia

    2015-07-01

    It is well established that adversities and GRIN2B (coding an N-methyl-D-aspartate receptor subunit) are independently associated with behavioral and cognitive impairments in childhood. However, a high proportion of children exposed to adversities have good, long-term outcomes. We hypothesized that among children exposed to adversities, GRIN2B variants would predict the worst cognitive and behavioral outcomes. 6 single nucleotide polymorphisms of GRIN2B were genotyped in 625 children aged 6-11 years from an Italian community-based sample. The interacting effect of GRIN2B variants with 4 measures of adversities [low socioeconomic status (SES), preterm delivery, maternal smoking during pregnancy, and absence of breastfeeding] was investigated upon blindly assessed cognitive abilities (vocabulary, block design, digit spans of Wechsler's Intelligence Scale, and Rey complex figure) and parents-rated behavioral problems (Child Behavior Checklist/6-18). Rs2268119 × SES interaction (Hotelling's Trace = 0.07; F(12,1154) = 3.53; p = 0.00004) influenced behavior, with more attention problems among children in the 'either A/T or T/T genotype and low SES' group, compared to all other groups. This interaction effect was not significant in an independent, replication sample of 475 subjects from an Italian community-based sample. GRIN2B variants predict children with the worst outcome in attention functioning among children exposed to low SES. Our findings, if replicated, could help in the identification of children with the highest risk and may prompt cost-effective preventive/treatment strategies. PMID:25316095

  13. ...und Einstein hatte doch recht

    NASA Astrophysics Data System (ADS)

    Will, Clifford M.; Leuchs, Anne; Leuchs, Gerd

    Keine wissenschaftliche Theorie ist auf solche Faszination auch außerhalb der Wissenschaft gestoßen wie die Allgemeine Relativitätstheorie von Albert Einstein, und keine wurde so nachdrücklich mit den Mitteln der modernen Physik überprüft. Wie hat sie diesen Test mit Raumsonden, Radioastronomie, Atomuhren und Supercomputern standgehalten? Hatte Einstein recht? Mit der Autorität des Fachmanns und dem Flair des unvoreingenommenen Erzählers schildert Clifford Will die Menschen, Ideen und Maschinen hinter den Tests der allgemeinen Relativitätstheorie. Ohne Formeln und Fachjargon wird der leser mit Einsteins Gedanken vertraut und erfährt von der Bestätigung seiner Vorhersagen, angefangen bei der Lichtablenkung im Schwerefeld der Sonne 1919 bis zu den ausgefeilten Kreiselexperimenten auf dem Space Shuttle. Die Allgemeine Relativitätstheorie hat nich nur alle diese Tests bestanden, sie hat darüber hinaus wesentlich beigetragen zu unserem Verständnis von Phänomenen wie Pulsaren, Quasaren, Schwarzen Löchern und Gravitationslinsen. Dieses Buch erzählt lebendig und spannend die Geschichte einer der größten geistigen Leistungen unserer Zeit.

  14. Pyropheophorbide und a as a catabolite of ethylene-induced chlorophyll und a degradation

    SciTech Connect

    Shimokawa, Keishi; Hashizume, Akihito ); Shioi, Yuzo )

    1990-05-01

    An enzyme extract prepared from ethylene-induced degreening Citrus fruits contains chlorophyll (Chl) degrading enzymes. The fate of Chl carbons during an enzymatic degradation was investigated using Chl {und a}-{sup 14}C. Accompanying the disappearance of labelled Chl {und a}, pheophorbide {und a} and pyropheophorbide {und a} appeared and accumulation of pyropheophorbide {und a} was observed. HydroxyChl {und a} was also detected, but this is thought to be an artifact during chromatography. Unlike ethylene-induced Citrus fruits (in vivo), further degradation of pyropheophorbide {und a} did not occur in vitro enzyme system. This suggests that there is a lack of enzyme(s) and/or cofactor(s) for further degradation. It is concluded that Chl {und a} degraded enzymatically by the following order: Chl {und a}, chlorophyllide {und a}, pheophorbide {und a} and pyropheophorbide {und a}.

  15. Mutations of the human interferon alpha-2b (hIFNα-2b) gene in cancer patients receiving radiotherapy

    PubMed Central

    Shahid, Saman; Chaudhry, Muhammad Nawaz; Mahmood, Nasir

    2015-01-01

    This research aimed to find out the impact of ionizing radiations on the hIFNα-2b gene of radiotherapy treated cancer patients. The gene hIFNα-2b synthesizes a protein which is an important anticancerous and antiviral protein. The cancer patients (breast, lung, thyroid, oral and prostate) who were undergoing a radiotherapy treatment were selected. A molecular analysis was performed for DNA isolation and gene amplification through PCR, to identify gene mutations. Further, by bioinformatics tools we concluded that how mutations identified in gene sequences have led to the alterations in the hINFα-2b protein in radiotherapy receiving cancer patients. The 32% mutations in the hINFα-2b gene were identified and all were frameshift mutations. Radiotherapy can impact the immune system and cancer patients may modulate their immunity. Understaning the mechanisms of radiotherapy-elicited immune response may be helpful in the development of those therapeutic interventions that can enhance the efficacy of radiotherapy. PMID:26396921

  16. Structural stability of W2B5 under high pressure

    NASA Astrophysics Data System (ADS)

    Kumar, N. R. Sanjay; Shekar, N. V. Chandra; Sahu, P. Ch.

    2015-05-01

    High-pressure structural stability studies have been carried out on tungsten boride W2B5 up to maximum pressure of 36 GPa using a Mao-Bell diamond-anvil cell at beamline BR-12 of the ELETTRA synchrotron facility (λ = 0.68881 Å). The hexagonal phase (S.G:P63/mmc) of W2B5 is stable up to the maximum pressure studied. The bulk modulus is estimated to be ~347 GPa using the Birch-Murnaghan equation of state. The variation of lattice parameters and bond lengths B-B and W-B have been studied and the c-axis is seen to be marginally more compressible than the a-axis.

  17. 40 CFR Table 2b to Subpart E of... - Reactivity Factors for Aliphatic Hydrocarbon Solvent Mixtures

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... Hydrocarbon Solvent Mixtures 2B Table 2B to Subpart E of Part 59 Protection of Environment ENVIRONMENTAL... Hydrocarbon Solvent Mixtures Bin Averageboiling point * (degrees F) Criteria Reactivityfactor 1 80-205 Alkanes... + Dry Point) / 2 (b) Aromatic Hydrocarbon Solvents...

  18. 40 CFR Table 2b to Subpart E of... - Reactivity Factors for Aliphatic Hydrocarbon Solvent Mixtures

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Hydrocarbon Solvent Mixtures 2B Table 2B to Subpart E of Part 59 Protection of Environment ENVIRONMENTAL... Hydrocarbon Solvent Mixtures Bin Averageboiling point * (degrees F) Criteria Reactivityfactor 1 80-205 Alkanes... + Dry Point) / 2 (b) Aromatic Hydrocarbon Solvents...

  19. Flux Line Lattice Structure in YNi2B2C

    NASA Astrophysics Data System (ADS)

    Kawano-Furukawa, Hazuki; Ohira-Kawamura, Seiko; Tsukagoshi, Hitomi; Kobayashi, Chiyako; Nagata, Takashi; Sakiyama, Naoki; Yoshizawa, Hideki; Yethiraj, Mohana; Suzuki, Jun-ichi; Takeya, Hiroyuki

    2008-10-01

    Recently Nakai et al. reported a theoretical H-T phase diagram of flux line lattice (FLL) structure in which successive transitions from a triangular, a square (\\squarev), a triangular and another square (\\squareg) occur with increasing a magnetic field. Here \\squarev and \\squareg indicate the FLL structures reflecting anisotropies in the Fermi velocity and the superconducting gap, respectively. In the case of YNi2B2C, \\squarev and \\squareg should rotate by 45°. The low field transition from triangular to \\squarev is observed in RENi2B2C (\\textit{RE}=Er, Tm, Lu, and Y). However, there is no experimental evidence for the appearance of \\squareg phase so far. We studied the FLL structure of YNi2B2C in the higher field region by small-angle neutron scattering. Our results show that a large area of the H-T phase diagram is occupied by \\squarev phase and there is no evidence for the appearance of \\squareg lattice.

  20. Agent-based services for B2B electronic commerce

    NASA Astrophysics Data System (ADS)

    Fong, Elizabeth; Ivezic, Nenad; Rhodes, Tom; Peng, Yun

    2000-12-01

    The potential of agent-based systems has not been realized yet, in part, because of the lack of understanding of how the agent technology supports industrial needs and emerging standards. The area of business-to-business electronic commerce (b2b e-commerce) is one of the most rapidly developing sectors of industry with huge impact on manufacturing practices. In this paper, we investigate the current state of agent technology and the feasibility of applying agent-based computing to b2b e-commerce in the circuit board manufacturing sector. We identify critical tasks and opportunities in the b2b e-commerce area where agent-based services can best be deployed. We describe an implemented agent-based prototype system to facilitate the bidding process for printed circuit board manufacturing and assembly. These activities are taking place within the Internet Commerce for Manufacturing (ICM) project, the NIST- sponsored project working with industry to create an environment where small manufacturers of mechanical and electronic components may participate competitively in virtual enterprises that manufacture printed circuit assemblies.

  1. Association of genetic variants of GRIN2B with autism.

    PubMed

    Pan, Yongcheng; Chen, Jingjing; Guo, Hui; Ou, Jianjun; Peng, Yu; Liu, Qiong; Shen, Yidong; Shi, Lijuan; Liu, Yalan; Xiong, Zhimin; Zhu, Tengfei; Luo, Sanchuan; Hu, Zhengmao; Zhao, Jingping; Xia, Kun

    2015-01-01

    Autism (MIM 209850) is a complex neurodevelopmental disorder characterized by social communication impairments and restricted repetitive behaviors. It has a high heritability, although much remains unclear. To evaluate genetic variants of GRIN2B in autism etiology, we performed a system association study of common and rare variants of GRIN2B and autism in cohorts from a Chinese population, involving a total sample of 1,945 subjects. Meta-analysis of a triad family cohort and a case-control cohort identified significant associations of multiple common variants and autism risk (Pmin = 1.73 × 10(-4)). Significantly, the haplotype involved with the top common variants also showed significant association (P = 1.78 × 10(-6)). Sanger sequencing of 275 probands from a triad cohort identified several variants in coding regions, including four common variants and seven rare variants. Two of the common coding variants were located in the autism-related linkage disequilibrium (LD) block, and both were significantly associated with autism (P < 9 × 10(-3)) using an independent control cohort. Burden analysis and case-only analysis of rare coding variants identified by Sanger sequencing did not find this association. Our study for the first time reveals that common variants and related haplotypes of GRIN2B are associated with autism risk. PMID:25656819

  2. Regulation of Human UGT2B15 and UGT2B17 by miR-376c in Prostate Cancer Cell Lines.

    PubMed

    Wijayakumara, Dhilushi D; Hu, Dong Gui; Meech, Robyn; McKinnon, Ross A; Mackenzie, Peter I

    2015-09-01

    Given the prime importance of UDP-glucuronosyltransferase (UGT) 2B15 and UGT2B17 in inactivating testosterone and dihydrotestosterone, control of their expression and activity in the prostate is essential for androgen signaling homeostasis in this organ. Although several studies provide evidence of transcriptional control of UGT2B15 and UGT2B17 by various endogenous and exogenous compounds, potential post-transcriptional regulation of UGT2B15 and UGT2B17 by microRNAs (miRs) in prostate cancer cells has not been examined. The present study identified a putative miR-376c target site in the 3'-untranslated regions (UTRs) of both UGT2B15 and UGT2B17 mRNAs. In accordance with the possibility that this miRNA negatively regulates UGT2B15 and UGT2B17 expression, there is an inverse correlation in the levels of miR-376c and UGT2B15/UGT2B17 mRNAs in prostate cancer cell lines versus normal prostate tissue. In LNCaP cells, transfection of miR-376c mimics inhibited the glucuronidations of testosterone, 4-methylumbelliferone (a substrate of UGT2B15), and androsterone (a substrate of UGT2B17). miR-376c reduced both UGT2B15 and UGT2B17 mRNA and protein levels and the activity of luciferase reporters containing UGT2B15 or UGT2B17 3'-UTRs. This microRNA-mediated repression was significantly abrogated by mutating the miR-376c binding site in the 3'-UTRs of both UGTs. Collectively, these data indicate that the expression of UGT2B15 and UGT2B17 is negatively regulated by the binding of miR-376c to the 3'-UTRs of UGT2B15 and UGT2B17 in prostate cancer cells. This represents the first evidence for post-transcriptional regulation of UGT2B15 and UGT2B17 by miRNAs in prostate cancer cells and may have importance in regulating androgen receptor signaling. PMID:26163549

  3. Beschallungstechnik, Beschallungsplanung und Simulation

    NASA Astrophysics Data System (ADS)

    Ahnert, Wolfgang; Goertz, Anselm

    Die primäre Aufgabe einer Lautsprecheranlage ist es, Musik, Sprache oder auch Signaltöne und Geräusche wiederzugeben. Diese können von einem Tonträger kommen (CD, Sprachspeicher), von einem anderen Ort übertragen (Zuspielung über Radio, TV, Telefon) oder vor Ort erzeugt werden. Letzteres umfasst Konzerte, Ansprachen, Durchsagen oder künstlerische Darbietungen, bei denen es meist darum geht, eine bereits vorhandene Quelle einer größeren oder weiter verteilten Anzahl von Personen zugänglich zu machen.

  4. MOLECULAR CHARACTERIZATION OF CYP2B6 SUBSTRATES

    PubMed Central

    Ekins, Sean; Iyer, Manisha; Krasowski, Matthew D.; Kharasch, Evan D.

    2008-01-01

    CYP2B6 has not been as fully characterized at the molecular level as other members of the human cytochrome P450 family. As more widely used in vitro probes for characterizing the involvement of this enzyme in the metabolism of xenobiotics have become available, the number of molecules identified as CYP2B6 substrates has increased. In this study we have analyzed the available kinetic data generated by multiple laboratories with human recombinant expressed CYP2B6 and along with calculated molecular properties derived from the ChemSpider database, we have determined the molecular features that appear to be important for CYP2B6 substrates. In addition we have applied 2D and 3D QSAR methods to generate predictive pharmacophore and 2D models. For 28 molecules with Km data, the molecular weight (mean ± SD) is 253.78±74.03, ACD/logP is 2.68±1.51, LogDpH 5.5 is 1.51±1.43, LogDpH 7.4 is 2.02±1.25, hydrogen bond donor (HBD) count is 0.57 ±0.57, hydrogen bond acceptor (HBA) count is 2.57±1.37, rotatable bonds is 3.50±2.71 and total polar surface area (TPSA) is 27.63±19.42. A second set of 15 molecules without Km data possessed similar mean molecular property values. These properties are comparable to those of a set of 21 molecules used in a previous pharmacophore modeling study (Ekins et al., J Pharmacol Exp Ther 288 (1), 21–29, 1999). Only the LogD and HBD values were statistically significantly different between these different datasets. We have shown that CYP2B6 substrates are generally small hydrophobic molecules that are frequently central nervous system active, which may be important for drug discovery research. PMID:18537573

  5. The ISS 2B PVTCS Ammonia Leak: An Operational History

    NASA Technical Reports Server (NTRS)

    Vareha, Anthony

    2014-01-01

    In 2006, the Photovoltaic Thermal Control System (PVTCS) for the International Space Station's 2B power channel began leaking ammonia at a rate of approximately 1.5lbm/year (out of a starting approximately 53lbm system ammonia mass). Initially, the operations strategy was "feed the leak," a strategy successfully put into action via Extra Vehicular Activity during the STS-134 mission. During this mission the system was topped off with ammonia piped over from a separate thermal control system. This recharge was to have allowed for continued power channel operation into 2014 or 2015, at which point another EVA would have been required. Without these periodic EVAs to refill the 2B coolant system, the channel would eventually leak enough fluid as to risk pump cavitation and system failure, resulting in the loss of the 2B power channel - the most critical of the Space Station's 8 power channels. In mid-2012, the leak rate increased to approximately 5lbm/year. Once discovered, an EVA was planned and executed within a 5 week timeframe to drastically alter the architecture of the PVTCS via connection to a dormant thermal control system not intended to be utilized as anything other than spare components. The purpose of this rerouting of the TCS was to increase system volume and to isolate the photovoltaic radiator, thought to be the likely leak source. This EVA was successfully executed on November 1st, 2012 and left the 2B PVTCS in a configuration where the system was now being adequately cooled via a totally different radiator than what the system was designed to utilize. Unfortunately, data monitoring over the next several months showed that the isolated radiator was not leaking, and the system itself continued to leak steadily until May 9th, 2013. It was on this day that the ISS crew noticed the visible presence of ammonia crystals escaping from the 2B channel's truss segment, signifying a rapid acceleration of the leak from 5lbm/year to 5lbm/day. Within 48 hours of the

  6. Anisotropic elastic and vibrational properties of Ru2B3 and Os2B3: a first-principles investigation

    NASA Astrophysics Data System (ADS)

    Ozisik, Haci; Deligoz, Engin; Surucu, Gokhan; Bogaz Ozisik, Havva

    2016-07-01

    The structural, mechanical and lattice dynamical properties of Ru2B3 and Os2B3 have been investigated by using a first-principles method based on the density functional theory within the generalized gradient approximation. The single crystal elastic constants are numerically estimated using strain–stress approach. The polycrystalline aggregate elastic parameters are calculated from the single elastic constants via the Voigt–Reuss–Hill approximations. Subsequently, the ductility and brittleness are characterized with the estimation from Pugh’s rule (B/G) and Cauchy pressure. Additionally, the Debye temperature is calculated from the average elastic wave velocity obtained from bulk and shear moduli. The calculated parameters are consistent with the previous experimental and theoretical data. These borides are both mechanically and dynamically stable in the considered structure.

  7. MED23: a new Mediator of H2B monoubiquitylation.

    PubMed

    Streubel, Gundula; Bracken, Adrian P

    2015-12-01

    The Mediator multiprotein complex physically links transcription factors to RNA polymerase II and the basal transcription machinery. While the Mediator complex has been shown to be required for transcriptional initiation and elongation, the understanding of its interplay with histone modifying enzymes and post‐translational modifications remains elusive. In this issue of The EMBO Journal, Yao et al (2015) report that the MED23 subunit of the Mediator complex physically associates with the heterodimeric RNF20/40 E3‐ligase complex to facilitate the monoubiquitylation of histone H2B on gene bodies of actively transcribed genes. PMID:26438725

  8. Renaturierung und Management von Heiden

    NASA Astrophysics Data System (ADS)

    Härdtle, Werner; Assmann, Thorsten; van Diggelen, Rudy; von Oheimb, Goddert

    Heiden zählen zu den ältesten und besonders reizvollen Kulturlandschaften Nordwesteuropas. Sie sind bezeichnend für nährstoffarme Böden in wintermilden Gebieten mit hohen Sommerniederschlägen. Während Heiden vor wenigen Jahrhunderten noch weit verbreitet und für manche Landschaften sogar prägend waren, hat sich ihr Areal heute auf wenige, meist in Naturschutzgebieten gelegene Restbestände verkleinert. Zu diesem Rückgang haben maßgeblich Änderungen der Landnutzung, aber auch Nährstoffeinträge aus umgebenden Agrarflächen und atmogene Depositionen beigetragen. In den meisten Ländern der Europäischen Union sind Heiden heute gesetzlich geschützte Ökosysteme, da diese, neben ihrem Erholungswert für den Menschen, Pflanzen- und Tierarten beherbergen, die außerhalb von Heiden nicht oder kaum überlebensfähig sind.

  9. Magnetospheric Multiscale Mission (MMS) Phase 2B Navigation Performance

    NASA Technical Reports Server (NTRS)

    Scaperoth, Paige Thomas; Long, Anne; Carpenter, Russell

    2009-01-01

    The Magnetospheric Multiscale (MMS) formation flying mission, which consists of four spacecraft flying in a tetrahedral formation, has challenging navigation requirements associated with determining and maintaining the relative separations required to meet the science requirements. The baseline navigation concept for MMS is for each spacecraft to independently estimate its position, velocity and clock states using GPS pseudorange data provided by the Goddard Space Flight Center-developed Navigator receiver and maneuver acceleration measurements provided by the spacecraft's attitude control subsystem. State estimation is performed onboard in real-time using the Goddard Enhanced Onboard Navigation System flight software, which is embedded in the Navigator receiver. The current concept of operations for formation maintenance consists of a sequence of two maintenance maneuvers that is performed every 2 weeks. Phase 2b of the MMS mission, in which the spacecraft are in 1.2 x 25 Earth radii orbits with nominal separations at apogee ranging from 30 km to 400 km, has the most challenging navigation requirements because, during this phase, GPS signal acquisition is restricted to less than one day of the 2.8-day orbit. This paper summarizes the results from high-fidelity simulations to determine if the MMS navigation requirements can be met between and immediately following the maintenance maneuver sequence in Phase 2b.

  10. Ressourceneinsatzplanung In der Energie- und Verfahrenstechnik

    NASA Astrophysics Data System (ADS)

    Engell, Sebastian; Handschin, Edmund; Rehtanz, Christian; Schultz, Rüdiger

    Der ökologisch nachhaltige, wirtschaftlich effiziente und politisch faire Umgang mit den Ressourcen der Erde ist eine der größten Herausforderungen an die Menschheit im 21. Jahrhundert und impliziert Paradigmenwechsel in allen Bereichen des gesellschaftlichen Lebens. Energie- und Verfahrenstechnik sind traditionell Bereiche, in denen der optimale Umgang mit kostbaren und beschränkt verfügbaren Ressourcen von erstrangiger Bedeutung ist. Zur Lösung der damit verbundenen komplexen Entscheidungsprobleme sind mathematische Methoden schon seit längerem im Einsatz. Hierbei können aber noch längst nicht alle bislang aufgetretenen Probleme fundiert angegangen werden. Der wachsende wirtschaftliche und ökologische Druck auf die Effizienz der Produktions-und Versorgungssysteme sowie stärkere Schwankungen von Angebot und Nachfrage führen zu neuen Herausforderungen, für die neue mathematische Methoden und Algorithmen entwickelt werden müssen.

  11. Welt und Wirkungsprinzip (2nd Aufl.)

    NASA Astrophysics Data System (ADS)

    Landgraf, Werner

    2010-03-01

    Modell einer kausalen Bewirkung der Welt, und logische, geometrische, physikalische Interprätation dieser Kausalmenge und Fortwirkung der frühsten ihrer sukzessiv als echt Neues bewirkten und durch Vorhandenes oder Späteres nicht darstellbaren oder widerrufbaren Ereignisse als Dimensionen und sie verkörpernde primäre Naturkräfte, mit Korrespondenz zur beobachteten Welt und ihrer grundlegendsten Eigenschaften. Wirklich ist nur was wirkt, wo und wie. Entsprechend ist im Bogenelement statt der Eigenzeit die variante Anzahl Wirkungen relevant, 0 ≈ 1/h2 dS2 - 1/tpl2 (dt2 - 1/c2 {dq12 + G02/G2 [dq2,32 - ...]}) mit G0 = c4lpl/Epl ≈ G. Die heutigen Dimensionen und Naturkräfte entstanden in dieser Reihenfolge, haben 'komplementäre' aber gleichwertige statische und dynamische Aspekte, entsprechend ihren Termen in Bogenelement bzw. Vierervektor, aus derem Vergleich sowie mit denen ihrer Nachbarn folgen Grundgleichungen bzw. Erhaltungssätze. Jeweils individuelle Eigenschaften wie ihre Naturkonstante konkretisieren sie und tragen zu gattungsmäßigen wie globale Affinität und Äquivalenzen bei. Ältestes Gebiet oder räumlicher Rand jeder Dimension sind die ersten vom Vorgänger bewirkten Ereignisse, selbst raumzeitlicher Ursprung des Nachfolgers, dort einmalig und ewig maximal rotverschoben fortwirkend und nicht lokalisierbar, um neue Elementareinheiten verschieden und lichtartig mit deren Verhältnis oder dem ihrer globalen Zustandsgrößen als konstanten Anfangsimpuls, Expansion, Längen- oder Ereignisdichte zueinander. Der Übergang vom diskreten Modell weniger Informationen zum Kontinuum und die Korrespondenz zur Physik ist problemlos, Details wie ein kontinuierlicher, abrupter oder ganz fehlender Abfall der Metrik beim ältesten Gebiet sind aber nur durch Beobachtungen entscheidbar. Erörtert werden allgemeine und individuelle Eigenschaften und ihre Konsequenzen der Dimensionen mit ihren Kräften, selbst und im Verhältnis zueinander, etwa ihrer begrenzten

  12. Structure of human nucleosome containing the testis-specific histone variant TSH2B

    SciTech Connect

    Urahama, Takashi; Horikoshi, Naoki; Osakabe, Akihisa; Tachiwana, Hiroaki; Kurumizaka, Hitoshi

    2014-03-25

    The crystal structure of human nucleosome containing the testis-specific TSH2B variant has been determined. The TSH2B Ser85 residue does not interact with H4 in the nucleosome, and induces a local structural difference between TSH2B and H2B in nucleosomes. The human histone H2B variant TSH2B is highly expressed in testis and may function in the chromatin transition during spermatogenesis. In the present study, the crystal structure of the human testis-specific nucleosome containing TSH2B was determined at 2.8 Å resolution. A local structural difference between TSH2B and canonical H2B in nucleosomes was detected around the TSH2B-specific amino-acid residue Ser85. The TSH2B Ser85 residue does not interact with H4 in the nucleosome, but in the canonical nucleosome the H2B Asn84 residue (corresponding to the TSH2B Ser85 residue) forms water-mediated hydrogen bonds with the H4 Arg78 residue. In contrast, the other TSH2B-specific amino-acid residues did not induce any significant local structural changes in the TSH2B nucleosome. These findings may provide important information for understanding how testis-specific histone variants form nucleosomes during spermatogenesis.

  13. Study of Subsonic Flow Over a TOW 2B Missile

    NASA Astrophysics Data System (ADS)

    Goudarzi, Koorosh; Jamali, Mehdi

    2016-01-01

    The objective of this investigation is to study the subsonic flow over a missile. In this paper, a model of TOW 2B missile is studied. Two computational approaches are being explored, namely solutions based on the Reynolds-averaged compressible Navier-Stokes equations and solutions based on the inviscid flow (small disturbance theory). The simulations are performed at the Mach number of 0.6, 0.7, 0.8, 0.9 and 1.0 at four angles of attack of 2, 4, 6 and 8 degree. Results obtained from analytical simulation are compared with numerical data. It is found that lift and drag coefficients would go up by increasing of the angle of attack and the Mach number. Trend of changes of the results that obtained from the small disturbance theory is roughly as same as the numeric solution.

  14. Integrated Product and Process Data for B2B Collaboration

    SciTech Connect

    Kulvatunyou, Boonserm; Ivezic, Nenad; Jones, Albert; Wysk, Richard A.

    2003-09-01

    Collaborative development of engineered products in a business-to-business (B2B) environment will require more than just the selection of components from an on-line catalogue. It will involve the electronic exchange of product, process, and production engineering information during both design and manufacturing. While the state-of-the-practice does include a variety of ways to exchange product data electronically, it does not extend to the exchange of manufacturing process data. The reason is simple; process data is usually tied to specific manufacturing resources. These resources are not known typically at product development time. This paper proposes an approach, called an Integrated Product and Process Data (IPPD), where manufacturing process data is considered during product development. This approach replaces traditional process plans, which are resource specific, with a resource-independent process representation. Such a representation will allow a much wider collaboration among business partners and provide the necessary base for collaborative product development.

  15. The cyclotron energization through auroral wave experiments (CENTAUR 2B)

    NASA Technical Reports Server (NTRS)

    Winningham, J. D.

    1992-01-01

    The CENTAUR 2B mission, a dual payload program, is in many aspects the same as the previous missions from Cape Perry and Norway in 1985. It was planned that these payloads would be launched from Andoya, Norway, Nov. 1989 from the Universal II launcher. The payloads are identical, but would have been launched at different azimuths as far north and as far west as possible. Particle experiments include the angular resolving energy analyzer (AREA), the fast ion mass spectrometer (FIMS), the spectrographic particle images (SPI), and finally, the differential ion flux probe (DIFP). SwRI was responsible for the scientific payload, which includes the power supplies, the power supply interfacing, the manipulating of the data from the instruments to format it for the telemetry system, all mechanical structure and restraint mechanisms, and the payload subskin. The status of the various components of this program is given.

  16. Semantic ETL into i2b2 with Eureka!

    PubMed

    Post, Andrew R; Krc, Tahsin; Rathod, Himanshu; Agravat, Sanjay; Mansour, Michel; Torian, William; Saltz, Joel H

    2013-01-01

    Clinical phenotyping is an emerging research information systems capability. Research uses of electronic health record (EHR) data may require the ability to identify clinical co-morbidities and complications. Such phenotypes may not be represented directly as discrete data elements, but rather as frequency, sequential and temporal patterns in billing and clinical data. These patterns' complexity suggests the need for a robust yet flexible extract, transform and load (ETL) process that can compute them. This capability should be accessible to investigators with limited ability to engage an IT department in data management. We have developed such a system, Eureka! Clinical Analytics. It extracts data from an Excel spreadsheet, computes a broad set of phenotypes of common interest, and loads both raw and computed data into an i2b2 project. A web-based user interface allows executing and monitoring ETL processes. Eureka! is deployed at our institution and is available for deployment in the cloud. PMID:24303265

  17. Semantic ETL into i2b2 with Eureka!

    PubMed Central

    Post, Andrew R.; Krc, Tahsin; Rathod, Himanshu; Agravat, Sanjay; Mansour, Michel; Torian, William; Saltz, Joel H.

    Clinical phenotyping is an emerging research information systems capability. Research uses of electronic health record (EHR) data may require the ability to identify clinical co-morbidities and complications. Such phenotypes may not be represented directly as discrete data elements, but rather as frequency, sequential and temporal patterns in billing and clinical data. These patterns’ complexity suggests the need for a robust yet flexible extract, transform and load (ETL) process that can compute them. This capability should be accessible to investigators with limited ability to engage an IT department in data management. We have developed such a system, Eureka! Clinical Analytics. It extracts data from an Excel spreadsheet, computes a broad set of phenotypes of common interest, and loads both raw and computed data into an i2b2 project. A web-based user interface allows executing and monitoring ETL processes. Eureka! is deployed at our institution and is available for deployment in the cloud. PMID:24303265

  18. Increased binding of circulating systemic lupus erythematosus autoantibodies to recombinant interferon alpha 2b.

    PubMed

    Khan, Wahid Ali; Qureshi, Javed Anwer

    2015-12-01

    Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease characterized by various types of immunological abnormalities including circulating and tissue-fixed autoantibodies reactive with autoantigens. The mechanism that can explain the production of these antibodies is unclear. Here we address the binding specificity of SLE autoantibodies with recombinant alpha interferon 2b (hrIFN α-2b), commercially available interferon (IFN α-2b), and the gene (cIFN α-2b) encoding this interferon. hrIFN α-2b showed higher binding with naturally occurring SLE autoantibodies as compared to IFN α-2b (p < 0.05) or cIFN α-2b gene (p < 0.001) as assessed by direct binding, inhibition ELISA, and quantitative precipitin titration. The relative affinity of SLE autoantibodies for hrIFN α-2b, IFN α-2b, and cIFN α-2b gene was in the order of 1.13 × 10(-7) , 1.38 × 10(-6) , and 1.22 × 10(-6) , respectively. hrIFN α-2b is shown to have unique epitopes that would explain the possible antigenic role of hrIFN α-2b in the generation of SLE autoantibodies. Anti-hrIFN α-2b antibodies have been shown to represent an alternative immunological probe for the estimation of interferon alpha 2b in the serum of SLE patients. PMID:26547367

  19. [Evidenzbasierte Leitlinien, Anspruch und Wirklichkeit].

    PubMed

    Gutsch, Johannes; Reif, Marcus; Müller-Hübenthal, Boris; Matthiessen, Peter F

    2016-01-01

    Mit der Konzeption der «Evidenzbasierten Medizin» und den «Evidenzbasierten Leitlinien» soll mithilfe von Formalisierungsprozeduren die ärztliche Irrtumsanfälligkeit kalkulierbar gemacht werden. Quantifizierte objektive Aussagen über die therapeutische Wirksamkeit einer Behandlung sollen die individuelle ärztliche Beurteilung der therapeutischen Wirksamkeit überflüssig machen. Damit kommt der Befolgung von formalen Regeln die entscheidende Rolle bei der Beantwortung der Frage nach dem Wahrheitsgehalt und dem Wirklichkeitsbezug zu. Im Rahmen evidenzbasierter Leitlinien werden vorrangig die Ergebnisse randomisierter kontrollierter Studien (RCT) oder Meta-Analysen solcher Studien herangezogen. Am Beispiel der S3-Leitlinie «Malignes Melanom» wird hier eine evidenzbasierte Urteilsbildung zur Wirksamkeit einer unkonventionellen Therapie - hier mit einem Mistelpräparat - analytisch nachvollzogen. Die für die Beurteilung dieser unkonventionellen Therapie herangezogene randomisierte Studie wird genauer methodisch analysiert. Obwohl sie keine statistisch basierte Aussage zulässt, wurde eine Leitlinienempfehlung auf Basis dieser Studie abgeleitet. Es wird gezeigt, dass 1) allein die Existenz einer einzigen RCT mit hoher Evidenz gleichgesetzt wird, 2) die Ergebnisse trotz beträchtlicher Fehlinterpretationen in eine S3-Leitlinie einfließen und 3) Meinungen anstelle kritischer wissenschaftlicher Analysen verarbeitet werden. Unsere Untersuchung zeigt, dass noch so ausgefeilte epistemologische und methodologische Formalien den Arzt nicht von der Pflicht entbinden, auf Basis seiner ärztlichen Erfahrung und professionellen Kompetenz den Realitätswert der ihm zur Verfügung stehenden Information zu beurteilen. PMID:27161555

  20. [Vegetarische und vegane Ernährung bei Kindern - Stand der Forschung und Forschungsbedarf].

    PubMed

    Keller, Markus; Müller, Stine

    2016-01-01

    Die Praxis vegetarischer Ernährungsformen ist in Deutschland im letzten Jahrzehnt deutlich angestiegen. Allerdings ist der Anteil vegetarischer und veganer Kinder dabei unbekannt. Studien mit Erwachsenen zeigen das präventive Potenzial, aber auch potenzielle Schwachstellen pflanzenbasierter Kostformen. Die Vorteile und Risiken einer vegetarischen bzw. veganen Ernährung im Kindesalter wurden bisher jedoch relativ selten untersucht. Außerdem lassen das unterschiedliche Alter der Kinder, das heterogene Studiendesign sowie die teilweise geringe Probandenzahl der Studien keine verbindlichen Aussagen zu. In dieser Übersichtsarbeit werden die Ergebnisse der wenigen Studien zu vegetarisch und vegan ernährten Kindern (< 12 Jahren) in Nordamerika und Europa zusammengefasst. Demnach lag die Zufuhr von Nahrungsenergie und Makronährstoffen vegetarischer und veganer Kinder meist näher an den Empfehlungen der Fachgesellschaften als die Ernährung gleichaltriger Mischkostkinder. Ebenso wiesen vegetarisch und vegan ernährte Kinder eine höhere Zufuhr von und bessere Versorgung mit verschiedenen Vitaminen und Mineralstoffen auf. Häufiger zeigten sich jedoch Defizite bei Vitamin B12, Zink, Kalzium, Eisen und Vitamin D. Das Wachstum und die Entwicklung vegetarisch und vegan ernährter Kinder entsprachen weitgehend den Referenzstandards, wobei sie dazu tendierten, leichter, schlanker und (< 5 Jahren) auch kleiner zu sein. Aufgrund der unzureichenden Studienlage besteht erheblicher Forschungsbedarf zu den Auswirkungen einer vegetarischen und veganen Ernährung im Kindesalter. PMID:27160086

  1. Restaurierung von Seen und Renaturierung von Seeufern

    NASA Astrophysics Data System (ADS)

    Grüneberg, Björn; Ostendorp, Wolfgang; Leßmann, Dieter; Wauer, Gerlinde; Nixdorf, Brigitte

    Süßwasserseen haben als ökosysteme und Lebensraum für Pflanzen und Tiere eine herausragende Bedeutung für die Artenvielfalt auf der Erde und prägen als Landschaftselemente unsere natürliche Umwelt. Seen fungieren als natürliche Stoffsenken, vor allem für Kohlenstoff und Nährstoffe, aber auch als Senken für in ihren Einzugsgebieten emittierte gelöste und feste Schadstoffe. Darüber hinaus ist Wasser eine wichtige Naturressource. Süßwasserseen stellen in den meisten Regionen der Erde lebenswichtige Quellen für die Versorgung mit Trinkwasser und tierischem Eiweiß (Fischfang) dar. Sie dienen als Wasserspeicher für die landwirtschaftliche und industrielle Nutzung. Auch für Erholungsaktivitäten des Menschen kommt ihnen eine große Bedeutung zu.

  2. Bewegungsapparat: Postcraniales Skelett und Muskulatur

    NASA Astrophysics Data System (ADS)

    Fischer, Martin S.

    Der Bewegungsapparat bestimmt die Form des Wirbeltierkörpers. So lässt sich z. B. aus der Gestalt eines Fisches auf seine bevorzugt e Schwimmweise schließen (S. 61). Bei den aquatisch en Schädeltieren dominiert die Fortbewegung mit axialem Antrieb; bei den meisten Tetrapoda findet sich eine Kombination aus axialem Antrieb und Bewegung durch Gliedmaßen. Selbst beim höchst spezialisierten Gang, der bipeden Bewegung des Menschen, sind Torsionsbewegungen des Rumpfes noch maßgeblich und bestimmen auch die Grundform des menschlichen Körpers (z. B. die Taille). Obwohl die verschiedenen Antriebsmechanismen eine funktionelle Einheit bilden, werden im Folgenden das Axialskelett sowie der Schulter- und Beckengürtel mit den zugehörigen Extremitäten getrennt besprochen.

  3. Molecular characterization of an. alpha. sub 2B -adrenergic receptor

    SciTech Connect

    Harrison, J.K.; Dewan Zeng; D'Angelo, D.D.; Tucker, A.L.; Zhihong Lu; Barber, C.M.; Lynch, K.R. )

    1990-02-26

    {alpha}{sub 2}-Adrenergic receptors comprise a heterogeneous population based on pharmacologic and molecular evidence. The authors have isolated a cDNA clone (pRNG{alpha}2) encoding a previously undescribed third subtype of an {alpha}{sub 2}-adrenergic receptor from a rat kidney cDNA library. The library was screened with an oligonucleotide encoding a highly conserved region found in all biogenic amine receptors described to date. The deduced amino acid sequence displays many features of G-protein coupled receptors with exception of the absence of the consensus N-linked glycosylation site at the amino terminus. Membranes prepared from COS-1 cells transfected with pRNG{alpha}2 display high affinity and saturable binding to {sup 3}H-rauwolscine (K{sub d}=2 nM).Competition curve data analysis shows that pRNG{alpha}2 protein binds to a variety of adrenergic drugs with the following rank order of potency: yohimbine {ge} cholorpromazine > prazosin {ge} clonidine > norepinephrine {ge} oxymetazoline. pRNG{alpha}2 RNA accumulates in both adult rat kidney and rat neonatal lung (predominant species is 4.0 kb). They conclude that pRNG{alpha}2 likely represents a cDNA for the {alpha}{sub 2B}-adrenergic receptor.

  4. BRI2 (ITM2b) Inhibits Aβ Deposition in Vivo

    PubMed Central

    Kim, Jungsu; Miller, Victor M.; Levites, Yona; West, Karen Jansen; Zwizinski, Craig W.; Moore, Brenda D.; Troendle, Fredrick J.; Bann, Maralyssa; Verbeeck, Christophe; Price, Robert W.; Smithson, Lisa; Sonoda, Leilani; Wagg, Kayleigh; Rangachari, Vijayaraghavan; Zou, Fanggeng; Younkin, Steven G.; Graff-Radford, Neill; Dickson, Dennis; Rosenberry, Terrone; Golde, Todd E.

    2008-01-01

    Analyses of the biologic effects of mutations in the BRI2 (ITM2b) and the amyloid β precursor protein (APP) genes support the hypothesis that cerebral accumulation of amyloidogenic peptides in familial British and familial Danish dementias and Alzheimer’s disease (AD) is associated with neurodegeneration. We have used somatic brain transgenic technology to express the BRI2 and BRI2-Aβ1-40 transgenes in amyloid β protein precursor (APP) mouse models. Expression of BRI2-Aβ1-40 mimics the suppressive effect previously observed using conventional transgenic methods, further validating the somatic brain transgenic methodology. Unexpectedly, we also find that expression of wild type human BRI2 reduces cerebral Aβ deposition in an AD mouse model. Additional data indicate that the 23 amino acid peptide, Bri23, released from BRI2 by normal processing is present in human cerebrospinal fluid (CSF), inhibits Aβ aggregation in vitro, and mediates its anti-amyloidogenic effect in vivo. These studies demonstrate that BRI2 is a novel mediator of Aβ deposition in vivo. PMID:18524908

  5. Remission of liver fibrosis by interferon-alpha 2b.

    PubMed

    Moreno, M G; Muriel, P

    1995-08-01

    Fibrosis is a dynamic process associated with the continuous deposition and resorption of connective tissue, mainly collagen. Therapeutic strategies are emerging by which this dynamic process can be modulated. Since interferons are known to inhibit collagen production, the aim of this study was to investigate if the administration of interferon-alpha 2b (IFN-alpha) can restore the normal hepatic content of collagen in rats with established fibrosis. Fibrosis was induced by prolonged bile duct ligation. IFN-alpha (100,000 IU/rat/day; s.c.) was administered to fibrotic rats for 15 days. Bile duct ligation increased liver collagen content 6-fold. In addition, serum and liver markers of hepatic injury increased significantly; liver histology showed an increase in collagen deposition, and the normal architecture was lost, with large zones of necrosis being observed frequently. IFN-alpha administration reversed to normal the values of all the biochemical markers measured and restored the normal architecture of the liver. Our results demonstrated that IFN-alpha is useful in reversing fibrosis and liver damage induced by biliary obstruction in the rat. However, further investigations are required to evaluate the therapeutic relevance of interferons on non-viral fibrosis and cholestasis. PMID:7646558

  6. [Obtaining and characteristics of domestic preparation interferon alpha-2b with prolonged effect].

    PubMed

    Pokholenko, Ia A; Porubleva, L V; Dubeĭ, I Ia; Rebriev, A V; Sutugina, L P; Gromovoĭ, T Iu; Pokrovskiĭ, V A; Obolenskaia, M Iu; Chernykh, S I

    2008-01-01

    Pegylated interferon alpha-2b (PEG-IFN alpha-2b) is a domestic preparation of a modified recombinant interferon alpha-2b with prolonged effect. The preparation was obtained by N-terminal pegylation of IFN alpha-2b with polyethylene glycol (PEG). This paper presents the method of PEG-IFN alpha-2b synthesis and characteristics of the obtained product. PAAG electrophoresis, Western blot analysis and MALDI-TOF mass-spectrometry confirm that the preparation is an N-terminal pegylated IFN alpha-2b that contains no more than 10% of dipegylated IFN alpha-2b. The comparison of PEG-IFN alpha-2b with its foreign analogue has revealed the similarity of their biological activity and pharmacokinetic parameters. PMID:19351063

  7. Functional characterization of cytochromes P450 2B from the desert woodrat Neotoma lepida

    PubMed Central

    Wilderman, P. Ross; Jang, Hyun-Hee; Malenke, Jael R.; Salib, Mariam; Angermeier, Elizabeth; Lamime, Sonia; Dearing, M. Denise; Halpert, James R.

    2014-01-01

    Mammalian detoxification processes have been the focus of intense research, but little is known about how wild herbivores process plant secondary compounds, many of which have medicinal value or are drugs. cDNA sequences that code for three enzymes of the cytochrome P450 (CYP) 2B subfamily, here termed 2B35, 2B36, and 2B37 have been recently identified from a wild rodent, the desert woodrat (Malenke et al., 2012). Two variant clones of each enzyme were engineered to increase protein solubility and to facilitate purification, as reported for CYP2B enzymes from multiple species. When expressed in E. coli each of the woodrat proteins gave the characteristic maximum at 450 nm in a reduced carbon monoxide difference spectrum but generally expressed at lower levels than rat CYP2B1. Two enzymes, 2B36 and 2B37, showed dealkylation activity with the model substrates 7-ethoxy-4-(trifluoromethyl)coumarin and 7-benzyloxyresorufin, whereas 2B35 was inactive. Binding of the monoterpene (+)-α-pinene produced a Type I shift in the absorbance spectrum of each enzyme. Mutation of 2B37 at residues 114, 262, or 480, key residues governing ligand interactions with other CYP2B enzymes, did not significantly change expression levels or produce the expected functional changes. In summary, two catalytic and one ligand-binding assay are sufficient to distinguish among CYP2B35, 2B36, and 2B37. Differences in functional profiles between 2B36 and 2B37 are partially explained by changes in substrate recognition site residue 114, but not 480. The results advance our understanding of the mechanisms of detoxification in wild mammalian herbivores and highlight the complexity of this system. PMID:24361551

  8. Beyond the exchange--the future of B2B.

    PubMed

    Wise, R; Morrison, D

    2000-01-01

    Using the Internet to facilitate business-to-business commerce promises many benefits, such as dramatic cost reductions and greater access to buyers and sellers. Yet little is known about how B2B e-commerce will evolve. The authors argue that changes in the financial services industry over the past two decades provide important clues. Exchanges, they say, are not the primary source of value in information-intensive markets; value tends to accumulate among a diverse group of specialists that focus on such tasks as packaging, standard setting, arbitrage, and information management. Because scale and liquidity are vitally important to efficient trading, today's exchanges will consolidate into a relatively small set of mega-exchanges. Originators will handle the origination and aggregation of complex transactions before sending them on to mega-exchanges for execution. E-speculators, seeking to capitalize on an abundance of market information, will tend to concentrate where relatively standardized products can be transferred easily among a large group of buyers. In many markets, a handful of independent solution providers with well-known brand names and solid reputations will thrive alongside mega-exchanges. Sell-side asset exchanges will create the networks and provide the tools to allow suppliers to trade orders among themselves, sometimes after initial transactions with customers are made on the mega-exchanges. For many companies, traditional skills in such areas as product development, manufacturing, and marketing may become relatively less important, while the ability to understand and capitalize on market dynamics may become considerably more important. PMID:11184979

  9. Maintenance therapy with interferon alfa 2b in Hodgkin's disease.

    PubMed

    Avilés, A; Díaz-Maqueo, J C; Talavera, A; Nambo, M J; García, E L

    1998-08-01

    We performed a randomized clinical trial to assess the efficacy and toxicity of interferon alfa 2b (IFN) as maintenance therapy in patients with advanced Hodgkin's disease in complete remission (CR) after conventional chemotherapy. One hundred and thirty-five patients (stage IIIB-IV B) were initially treated with EBVD (epirubicin, bleomycin, vinblastine, dacarbazine). IF CR was achieved they were randomly assigned to receive either maintenance therapy with IFN 5.0 MU three times a week for one year or no further treatment (control group). Clinical and laboratory characteristics at diagnosis were quite similar in both groups. After a median follow-up of 74.3 months (range 49 to 108), 61 out of 68 patients (91%; 95% confidence interval (CI): 76% to 97%) remain in first complete remission in the IFN-treated group compared to 38 out of 67 (58%; 95% CI: 49% to 71%) in the control group (p<.01). Overall survival was also better in the IFN treated group: 62 patients (92%; 95% CI: 82% to 97%) are alive free of disease at 7-years compared to 40 patients (67%, 95%: 55% to 76%) in the control group (p<.01). Toxicity secondary to IFN administration was mild and no dose modification was necessary during treatment. All patients received the planned dose of IFN. This was not an intent-to treat analysis. IFN administration as maintenance therapy was appears to be the only cause of improvement in outcome in these patients. We feel that IFN should be considered as maintenance therapy in patients with advanced Hodgkin's disease because this treatment improves the final outcome without the excessive toxicities of more aggressive therapeutic approaches such as bone marrow transplantation during first CR. We hope that IFN will be considered in future randomized clinical trials in order to define it's role in the treatment of Hodgkin's disease. PMID:9711927

  10. 40 CFR Table 2b to Subpart E of... - Reactivity Factors for Aliphatic Hydrocarbon Solvent Mixtures

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... Hydrocarbon Solvent Mixtures 2B Table 2B to Subpart E of Part 59 Protection of Environment ENVIRONMENTAL... Hydrocarbon Solvent Mixtures Bin Averageboiling point* (degrees F) Criteria Reactivityfactor (g O3/g VOC) 1 80... Point + Dry Point)/2(b) Aromatic Hydrocarbon Solvents...

  11. 40 CFR Table 2b to Subpart E of... - Reactivity Factors for Aliphatic Hydrocarbon Solvent Mixtures

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... Hydrocarbon Solvent Mixtures 2B Table 2B to Subpart E of Part 59 Protection of Environment ENVIRONMENTAL... Hydrocarbon Solvent Mixtures Bin Averageboiling point* (degrees F) Criteria Reactivityfactor (g O3/g VOC) 1 80... Point + Dry Point)/2(b) Aromatic Hydrocarbon Solvents...

  12. 40 CFR Table 2b to Subpart E of... - Reactivity Factors for Aliphatic Hydrocarbon Solvent Mixtures

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... Hydrocarbon Solvent Mixtures 2B Table 2B to Subpart E of Part 59 Protection of Environment ENVIRONMENTAL... Hydrocarbon Solvent Mixtures Bin Averageboiling point* (degrees F) Criteria Reactivityfactor (g O3/g VOC) 1 80... Point + Dry Point)/2(b) Aromatic Hydrocarbon Solvents...

  13. 14 CFR 250.2b - Carriers to request volunteers for denied boarding.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 14 Aeronautics and Space 4 2013-01-01 2013-01-01 false Carriers to request volunteers for denied boarding. 250.2b Section 250.2b Aeronautics and Space OFFICE OF THE SECRETARY, DEPARTMENT OF TRANSPORTATION (AVIATION PROCEEDINGS) ECONOMIC REGULATIONS OVERSALES § 250.2b Carriers to request volunteers for...

  14. Lineare und verzweigte Blockcopolymere aus Polypeptiden und synthetischen Polymeren

    NASA Astrophysics Data System (ADS)

    Kukula, Hildegard

    2001-07-01

    Die vorliegende Arbeit beschäftigt sich mit der Synthese und den Eigenschaften von linearen und verzweigten amphiphilen Polypeptid-Blockcopolymeren. Die Frage nach dem Einfluss der Topologie und Konformation der Blockcopolymere auf die supramolekularen und kolloidalen Eigenschaften bildete einen wichtigen Aspekt bei den Untersuchungen. Die Blockcopolymere wurden nach einem mehrstufigen Reaktionsschema durch Kombination von anionischer und ringöffnender Polymerisation von Aminosäuren-N-Carboxyanhydriden (NCA) synthetisiert. Die Untersuchung der Polypeptid-Blockcopolymere hinsichtlich ihres Aggregationsverhaltens in fester Phase sowie in verdünnter wässriger Lösung erfolgte mittels Streumethoden (SAXS, WAXS, DLS) sowie abbildender Methoden (TEM). Durch Einsatz der Blockcopolymere als polymere Stabilisatoren in der Emulsionspolymerisation wurden Oberflächen funktionalisierte Latizes erhalten. Als Beispiel für eine pharmazeutische Anwendung wurden bioverträgliche Polypeptid-Blockcopolymere als Wirkstoff-Trägersysteme in der Krebstherapie eingesetzt. This work describes the synthesis and characterization of linear and branched polypeptide block copolymers having amphiphilic character. The studies focused on the impact of the block copolymers' conformation and architecture on the supramolecular and colloidal properties. The polypeptide block copolymers were prepared in a multi-step process involving the anionic synthesis of (poly)amino-functional polymers (polystyrene and polybutadiene) which where used as macroinitiators for the ring-opening polymerization of N-carboxyanhydrides (NCA) of protected a-aminoacids. Supramolecular structures of the block copolymers in the solid state as well as in diluted aqueous solution were investigated using scattering (SAXS, WAXS, DLS) and microscopic (TEM) methods. Both linear and branched polypeptide block copolymers were used as polymeric stabilizers in the emulsion polymerization of styrene to yield polypeptide

  15. Dynamische Motorvermessung mit verschiedenen Methoden und Modellen

    NASA Astrophysics Data System (ADS)

    Schreiber, Alexander

    Die stark zunehmenden gesetzlichen und wirtschaftlichen Vorgaben zur Senkung von Kraftstoffverbrauch und Abgasemissionen stellen große Anforderungen an die weitere Entwicklung von Benzin- und Dieselmotoren. Hierbei sind grundlegende Fortschritte durch Konstruktion und auslegungsbedingte Maßnahmen im Bereich der Einspritzung, Gemischaufbereitung, Aufladung, Brennverfahren und Abgasnachbehandlung zu erreichen. Ein wesentlicher Teil dieser Verbesserungen wird jedoch durch eine Zunahme von Variabilitäten erreicht wie z.B. verstellbaren Vor-, Haupt- und Nacheinspritzungen, variablem Raildruck, variablen Nockenwellensteuerwinkeln, Ventilhüben, Drall-/Tumbleklappen sowie verstellbaren Abgasturbinen, Abgasrückführströmen und Abgasnachbehandlungssystemen. Dadurch steigt die Zahl der Stellglieder (Aktoren) stark an. Hinzu kommen zusätzliche Sensoren wie z.B. für Luftzahl, NOx, Brennraumdruck, Abgastemperatur und Abgasdruck. Deshalb nimmt der Umfang der Steuerungs-, Regelungs- und Diagnosefunktionen in der Motorelektronik (ECU) stark zu. Bild 7-1 zeigt als Beispiel den Signalfluss für die gesteuerten und geregelten Größen eines Dieselmotors in einer beispielhaften Prüfstandsumgebung.

  16. Distinct roles of NR2A and NR2B cytoplasmic tails in long term potentiation

    PubMed Central

    Foster, Kelly A.; McLaughlin, Nathan; Edbauer, Dieter; Phillips, Marnie; Bolton, Andrew; Constantine-Paton, Martha; Sheng, Morgan

    2010-01-01

    NMDA receptors (NMDARs) are critical mediators of activity-dependent synaptic plasticity, but the differential roles of NR2A- versus NR2B-containing NMDARs have been controversial. Here, we investigate the roles of NR2A and NR2B in LTP in organotypic hippocampal slice cultures using RNAi and overexpression, to complement pharmacological approaches. In young slices, when NR2B is the predominant subunit expressed, LTP is blocked by the NR2B-selective antagonist Ro25-6981. As slices mature, and NR2A expression rises, activation of NR2B receptors became no longer necessary for LTP induction. LTP was blocked, however, by RNAi knockdown of NR2B, and this was rescued by coexpression of an RNAi-resistant NR2B (NR2B*) cDNA. Interestingly, a chimeric NR2B subunit in which the C-terminal cytoplasmic tail was replaced by that of NR2A failed to rescue LTP while the reverse chimera, NR2A channel with NR2B tail, was able to restore LTP. Thus expression of NR2B with its intact cytoplasmic tail is required for LTP induction, at an age when channel activity of NR2B-NMDARs is not required for LTP. Overexpression of wildtype NR2A failed to rescue LTP in neurons transfected with NR2B-RNAi construct, despite restoring NMDA-EPSC amplitude to a similar level as NR2B*. Surprisingly, an NR2A construct lacking its entire C-terminal cytoplasmic tail regained its ability to restore LTP. Together these data suggest that the NR2B subunit plays a critical role for LTP, presumably by recruiting relevant molecules important for LTP via its cytoplasmic tail. By contrast, NR2A is not essential for LTP and its cytoplasmic tail seems to carry inhibitory factors for LTP. PMID:20164351

  17. Postsynaptic density protein 95-regulated NR2B tyrosine phosphorylation and interactions of Fyn with NR2B in levodopa-induced dyskinesia rat models

    PubMed Central

    Ba, Maowen; Kong, Min; Ma, Guozhao

    2015-01-01

    Context Abnormality in interactions between N-methyl-d-aspartate (NMDA) receptor and its signaling molecules occurs in the lesioned striatum in Parkinson’s disease (PD) and levodopa-induced dyskinesia (LID). It was reported that Fyn-mediated NR2B tyrosine phosphorylation, can enhance NMDA receptor function. Postsynaptic density protein 95 (PSD-95), one of the synapse-associated proteins, regulates interactions between receptor and downstream-signaling molecules. In light of the relationship between PSD-95, NR2B, and Fyn kinases, does PSD-95 contribute to the overactivity of NMDA receptor function induced by dopaminergic treatment? To further prove the possibility, the effects of regulating the PSD-95 expression on the augmented NR2B tyrosine phosphorylation and on the interactions of Fyn and NR2B in LID rat models were evaluated. Methods In the present study, parkinsonian rat models were established by injecting 6-hydroxydopamine. Subsequently, valid PD rats were treated with levodopa (50 mg/kg/day with benserazide 12.5 mg/kg/day, twice daily) intraperitoneally for 22 days to create LID rat models. Then, the effect of pretreatment with an intrastriatal injection of the PSD-95mRNA antisense oligonucleotides (PSD-95 ASO) on the rotational response to levodopa challenge was assessed. The effects of pretreatment with an intrastriatal injection of PSD-95 ASO on the augmented NR2B tyrosine phosphorylation and interactions of Fyn with NR2B in the LID rat models were detected by immunoblotting and immunoprecipitation. Results Levodopa administration twice daily for 22 days to parkinsonian rats shortened the rotational duration and increased the peak turning responses. The altered rotational responses were attenuated by PSD-95 ASO pretreatment. Meanwhile, PSD-95 ASO pretreatment decreased the level of PSD-95 protein expression and reduced both the augmented NR2B tyrosine phosphorylation and interactions of Fyn with NR2B triggered during the levodopa administration in the

  18. Copy Number Variation of UGT 2B Genes in Indian Families Using Whole Genome Scans

    PubMed Central

    Veerappa, Avinash M.; Padakannaya, Prakash; Ramachandra, Nallur B.

    2016-01-01

    Background and Objectives. Uridine diphospho-glucuronosyltransferase 2B (UGT2B) is a family of genes involved in metabolizing steroid hormones and several other xenobiotics. These UGT2B genes are highly polymorphic in nature and have distinct polymorphisms associated with specific regions around the globe. Copy number variations (CNVs) status of UGT2B17 in Indian population is not known and their disease associations have been inconclusive. It was therefore of interest to investigate the CNV profile of UGT2B genes. Methods. We investigated the presence of CNVs in UGT2B genes in 31 members from eight Indian families using Affymetrix Genome-Wide Human SNP Array 6.0 chip. Results. Our data revealed >50% of the study members carried CNVs in UGT2B genes, of which 76% showed deletion polymorphism. CNVs were observed more in UGT2B17 (76.4%) than in UGT2B15 (17.6%). Molecular network and pathway analysis found enrichment related to steroid metabolic process, carboxylesterase activity, and sequence specific DNA binding. Interpretation and Conclusion. We report the presence of UGT2B gene deletion and duplication polymorphisms in Indian families. Network analysis indicates the substitutive role of other possible genes in the UGT activity. The CNVs of UGT2B genes are very common in individuals indicating that the effect is neutral in causing any suspected diseases. PMID:27092269

  19. Cloning and chromosomal localization of the human A{sub 2b} adenosine receptor gene (ADORA2B) and its pseudogene

    SciTech Connect

    Jacobson, M.A.; Johnson, R.G.; Luneau, C.J.

    1995-05-20

    To determine the chromosomal localization of the human A{sub 2b} adenosine receptor, the corresponding genomic clone was isolated and used as a probe for fluorescence in situ hybridization to metaphase chromosomes. Partial sequence analysis of the A{sub 2b} gene (ADORA2B) revealed an intron that interrupted the coding region corresponding to the second intracellular loop similar to that reported for A{sub 1} and A{sub 2a} adenosine receptor genes. A pseudogene for the A{sub 2b} receptor was also identified; it exhibited 79% identity to the A{sub 2b} adenosine receptor cDNA coding sequence and contained multiple deletions, point mutations, and frame shifts and two in-frame stops. These changes would result in the inability to encode a functional receptor. The genomic clones were utilized to localize the A{sub 2b} receptor to chromosome 17p12 and the A{sub 2b} pseudogene to chromosome 1q32. 15 refs., 1 fig.

  20. Functional characterization of cytochromes P450 2B from the desert woodrat Neotoma lepida

    SciTech Connect

    Wilderman, P. Ross; Jang, Hyun-Hee; Malenke, Jael R.; Salib, Mariam; Angermeier, Elisabeth; Lamime, Sonia; Dearing, M. Denise; Halpert, James R.

    2014-02-01

    Mammalian detoxification processes have been the focus of intense research, but little is known about how wild herbivores process plant secondary compounds, many of which have medicinal value or are drugs. cDNA sequences that code for three enzymes of the cytochrome P450 (CYP) 2B subfamily, here termed 2B35, 2B36, and 2B37 have been recently identified from a wild rodent, the desert woodrat (Malenke et al., 2012). Two variant clones of each enzyme were engineered to increase protein solubility and to facilitate purification, as reported for CYP2B enzymes from multiple species. When expressed in Escherichia coli each of the woodrat proteins gave the characteristic maximum at 450 nm in a reduced carbon monoxide difference spectrum but generally expressed at lower levels than rat CYP2B1. Two enzymes, 2B36 and 2B37, showed dealkylation activity with the model substrates 7-ethoxy-4-(trifluoromethyl)coumarin and 7-benzyloxyresorufin, whereas 2B35 was inactive. Binding of the monoterpene (+)-α-pinene produced a Type I shift in the absorbance spectrum of each enzyme. Mutation of 2B37 at residues 114, 262, or 480, key residues governing ligand interactions with other CYP2B enzymes, did not significantly change expression levels or produce the expected functional changes. In summary, two catalytic and one ligand-binding assay are sufficient to distinguish among CYP2B35, 2B36, and 2B37. Differences in functional profiles between 2B36 and 2B37 are partially explained by changes in substrate recognition site residue 114, but not 480. The results advance our understanding of the mechanisms of detoxification in wild mammalian herbivores and highlight the complexity of this system. - Highlights: • Three CYP2B enzymes from Neotoma lepida were cloned, engineered, and expressed. • A mix of catalytic and binding assays yields unique results for each enzyme. • Mutational analysis indicates CYP{sub 2}B substrate recognition remains to be clarified. • Reported N. lepida gene

  1. Nrk2b-mediated NAD+ production regulates cell adhesion and is required for muscle morphogenesis in vivo: Nrk2b and NAD+ in muscle morphogenesis.

    PubMed

    Goody, Michelle F; Kelly, Meghan W; Lessard, Kevin N; Khalil, Andre; Henry, Clarissa A

    2010-08-15

    Cell-matrix adhesion complexes (CMACs) play fundamental roles during morphogenesis. Given the ubiquitous nature of CMACs and their roles in many cellular processes, one question is how specificity of CMAC function is modulated. The clearly defined cell behaviors that generate segmentally reiterated axial skeletal muscle during zebrafish development comprise an ideal system with which to investigate CMAC function during morphogenesis. We found that Nicotinamide riboside kinase 2b (Nrk2b) cell autonomously modulates the molecular composition of CMACs in vivo. Nrk2b is required for normal Laminin polymerization at the myotendinous junction (MTJ). In Nrk2b-deficient embryos, at MTJ loci where Laminin is not properly polymerized, muscle fibers elongate into adjacent myotomes and are abnormally long. In yeast and human cells, Nrk2 phosphorylates Nicotinamide Riboside and generates NAD+ through an alternative salvage pathway. Exogenous NAD+ treatment rescues MTJ development in Nrk2b-deficient embryos, but not in laminin mutant embryos. Both Nrk2b and Laminin are required for localization of Paxillin, but not beta-Dystroglycan, to CMACs at the MTJ. Overexpression of Paxillin in Nrk2b-deficient embryos is sufficient to rescue MTJ integrity. Taken together, these data show that Nrk2b plays a specific role in modulating subcellular localization of discrete CMAC components that in turn plays roles in musculoskeletal development. Furthermore, these data suggest that Nrk2b-mediated synthesis of NAD+ is functionally upstream of Laminin adhesion and Paxillin subcellular localization during MTJ development. These results indicate a previously unrecognized complexity to CMAC assembly in vivo and also elucidate a novel role for NAD+ during morphogenesis. PMID:20566368

  2. Protein 2B of Coxsackievirus B3 Induces Autophagy Relying on Its Transmembrane Hydrophobic Sequences

    PubMed Central

    Wu, Heng; Zhai, Xia; Chen, Yang; Wang, Ruixue; Lin, Lexun; Chen, Sijia; Wang, Tianying; Zhong, Xiaoyan; Wu, Xiaoyu; Wang, Yan; Zhang, Fengmin; Zhao, Wenran; Zhong, Zhaohua

    2016-01-01

    Coxsackievirus B (CVB) belongs to Enterovirus genus within the Picornaviridae family, and it is one of the most common causative pathogens of viral myocarditis in young adults. The pathogenesis of myocarditis caused by CVB has not been completely elucidated. In CVB infection, autophagy is manipulated to facilitate viral replication. Here we report that protein 2B, one of the non-structural proteins of CVB3, possesses autophagy-inducing capability. The autophagy-inducing motif of protein 2B was identified by the generation of truncated 2B and site-directed mutagenesis. The expression of 2B alone was sufficient to induce the formation of autophagosomes in HeLa cells, while truncated 2B containing the two hydrophobic regions of the protein also induced autophagy. In addition, we demonstrated that a single amino acid substitution (56V→A) in the stem loop in between the two hydrophobic regions of protein 2B abolished the formation of autophagosomes. Moreover, we found that 2B and truncated 2B with autophagy-inducting capability were co-localized with LC3-II. This study indicates that protein 2B relies on its transmembrane hydrophobic regions to induce the formation of autophagosomes, while 56 valine residue in the stem loop of protein 2B might exert critical structural influence on its two hydrophobic regions. These results may provide new insight for understanding the molecular mechanism of autophagy triggered by CVB infection. PMID:27187444

  3. Protein 2B of Coxsackievirus B3 Induces Autophagy Relying on Its Transmembrane Hydrophobic Sequences.

    PubMed

    Wu, Heng; Zhai, Xia; Chen, Yang; Wang, Ruixue; Lin, Lexun; Chen, Sijia; Wang, Tianying; Zhong, Xiaoyan; Wu, Xiaoyu; Wang, Yan; Zhang, Fengmin; Zhao, Wenran; Zhong, Zhaohua

    2016-01-01

    Coxsackievirus B (CVB) belongs to Enterovirus genus within the Picornaviridae family, and it is one of the most common causative pathogens of viral myocarditis in young adults. The pathogenesis of myocarditis caused by CVB has not been completely elucidated. In CVB infection, autophagy is manipulated to facilitate viral replication. Here we report that protein 2B, one of the non-structural proteins of CVB3, possesses autophagy-inducing capability. The autophagy-inducing motif of protein 2B was identified by the generation of truncated 2B and site-directed mutagenesis. The expression of 2B alone was sufficient to induce the formation of autophagosomes in HeLa cells, while truncated 2B containing the two hydrophobic regions of the protein also induced autophagy. In addition, we demonstrated that a single amino acid substitution (56V→A) in the stem loop in between the two hydrophobic regions of protein 2B abolished the formation of autophagosomes. Moreover, we found that 2B and truncated 2B with autophagy-inducting capability were co-localized with LC3-II. This study indicates that protein 2B relies on its transmembrane hydrophobic regions to induce the formation of autophagosomes, while 56 valine residue in the stem loop of protein 2B might exert critical structural influence on its two hydrophobic regions. These results may provide new insight for understanding the molecular mechanism of autophagy triggered by CVB infection. PMID:27187444

  4. CULTURE CONDITIONS PROFOUNDLY IMPACT PHENOTYPE IN BEAS-2B, A HUMAN PULMONARY EPITHELIAL MODEL

    PubMed Central

    Zhao, Fei; Klimecki, Walter T.

    2015-01-01

    BEAS-2B, an immortalized, human lung epithelial cell line, has been used to model pulmonary epithelial function for over 30 years. The BEAS-2B phenotype can be modulated by culture conditions that include the presence or absence of fetal bovine serum (FBS). The popularity of BEAS-2B as a model of arsenic toxicology, and the common use of BEAS-2B cultured both with and without FBS, led us to investigate the impact of FBS on BEAS-2B in the context of arsenic toxicology. Comparison of genome-wide gene expression in BEAS-2B cultured with or without FBS revealed altered expression in several biological pathways, including those related to carcinogenesis and energy metabolism. Real-time measurements of oxygen consumption and glycolysis in BEAS-2B demonstrated that FBS culture conditions were associated with a 1.4-fold increase in total glycolytic capacity, a 1.9-fold increase in basal respiration, a 2.0-fold increase in oxygen consumed for ATP production, and a 2.8-fold increase in maximal respiration, compared to BEAS-2B cultured without FBS. Comparisons of the transcriptome changes in BEAS-2B resulting from FBS exposure to the transcriptome changes resulting from exposure to 1 μM sodium arsenite revealed that mRNA levels of 43% of the arsenite-modulated genes were also modulated by FBS. Cytotoxicity studies revealed that BEAS-2B cells exposed to 5% FBS for 8 weeks were almost 5 times more sensitive to arsenite cytotoxicity than non-FBS-exposed BEAS-2B cells. Phenotype changes induced in BEAS-2B by FBS suggest that culture conditions should be carefully considered when using BEAS-2B as an experimental model of arsenic toxicity. PMID:25524072

  5. Impacts of the Glucuronidase Genotypes UGT1A4, UGT2B7, UGT2B15 and UGT2B17 on Tamoxifen Metabolism in Breast Cancer Patients.

    PubMed

    Romero-Lorca, Alicia; Novillo, Apolonia; Gaibar, María; Bandrés, Fernando; Fernández-Santander, Ana

    2015-01-01

    Tamoxifen is used to prevent and treat estrogen-dependent breast cancer. It is described as a prodrug since most of its antiestrogen effects are exerted through its hydroxylated metabolites 4-OH-tamoxifen and endoxifen. In prior work, we correlated optimal plasma levels of these metabolites with certain genotypes of CYP2D6 and SULT1A2. This descriptive study examines correlations between concentrations of tamoxifen's glucuronide metabolites and genotypes UGT1A4 Pro24Thr, UGT1A4 Leu48Val, UGT2B7 His268Tyr, UGT2B15 Asp85YTyr UGT2B15 Lys523Thr and UGT2B17del in 132 patients with estrogen receptor-positive breast cancer under treatment with tamoxifen. Patients were genotyped by real-time and conventional PCR-RFLP. The glucuronides 4-OH-tamoxifen-N-glucuronide, 4-OH-tamoxifen-O-glucuronide and endoxifen-O-glucuronide were isolated from blood plasma and quantified using a high-pressure liquid chromatography-tandem mass spectrometry system. Individuals who were homozygous for UGT1A448VAL showed significantly lower mean concentrations of both glucuronide metabolites compared to subjects genotyped as wt/wt plus wt/48Val (p=0.037 and p=0.031, respectively). Women homozygous for UGT2B7268Tyr also showed mean substrate/product ratios of 4-OH-tamoxifen/4-OH-tamoxifen-O-glucuronide and 4-OH-tamoxifen/4-OH-tamoxifen-N-glucuronide indicative of reduced glucuronidase activity compared to wt homozygotes or to heterozygotes for the polymorphism (p=0.005 and p=0.003, respectively). In contrast, UGT2B15 Lys523Thr and UGT2B17del were associated with possibly increased enzyme activity. Patients with at least one variant allele UGT2B15523Thr showed significantly higher 4-OH-tamoxifen-O-glucuronide and endoxifen-glucuronide levels (p=0.023 and p=0.025, respectively) indicating a variant gene-dose effect. Higher 4-OH-tamoxifen-N-glucuronide levels observed in UGT2B17del genotypes (p=0.042) could be attributed to a mechanism that compensates for the greater expression of other genes in UGT2B

  6. Impacts of the Glucuronidase Genotypes UGT1A4, UGT2B7, UGT2B15 and UGT2B17 on Tamoxifen Metabolism in Breast Cancer Patients

    PubMed Central

    Romero-Lorca, Alicia; Novillo, Apolonia; Gaibar, María; Bandrés, Fernando; Fernández-Santander, Ana

    2015-01-01

    Tamoxifen is used to prevent and treat estrogen-dependent breast cancer. It is described as a prodrug since most of its antiestrogen effects are exerted through its hydroxylated metabolites 4-OH-tamoxifen and endoxifen. In prior work, we correlated optimal plasma levels of these metabolites with certain genotypes of CYP2D6 and SULT1A2. This descriptive study examines correlations between concentrations of tamoxifen's glucuronide metabolites and genotypes UGT1A4 Pro24Thr, UGT1A4 Leu48Val, UGT2B7 His268Tyr, UGT2B15 Asp85YTyr UGT2B15 Lys523Thr and UGT2B17del in 132 patients with estrogen receptor-positive breast cancer under treatment with tamoxifen. Patients were genotyped by real-time and conventional PCR-RFLP. The glucuronides 4-OH-tamoxifen-N-glucuronide, 4-OH-tamoxifen-O-glucuronide and endoxifen-O-glucuronide were isolated from blood plasma and quantified using a high-pressure liquid chromatography-tandem mass spectrometry system. Individuals who were homozygous for UGT1A448VAL showed significantly lower mean concentrations of both glucuronide metabolites compared to subjects genotyped as wt/wt plus wt/48Val (p=0.037 and p=0.031, respectively). Women homozygous for UGT2B7268Tyr also showed mean substrate/product ratios of 4-OH-tamoxifen/4-OH-tamoxifen-O-glucuronide and 4-OH-tamoxifen/4-OH-tamoxifen-N-glucuronide indicative of reduced glucuronidase activity compared to wt homozygotes or to heterozygotes for the polymorphism (p=0.005 and p=0.003, respectively). In contrast, UGT2B15 Lys523Thr and UGT2B17del were associated with possibly increased enzyme activity. Patients with at least one variant allele UGT2B15523Thr showed significantly higher 4-OH-tamoxifen-O-glucuronide and endoxifen-glucuronide levels (p=0.023 and p=0.025, respectively) indicating a variant gene-dose effect. Higher 4-OH-tamoxifen-N-glucuronide levels observed in UGT2B17del genotypes (p=0.042) could be attributed to a mechanism that compensates for the greater expression of other genes in UGT2B

  7. Multiple roles for UDP-glucuronosyltransferase (UGT)2B15 and UGT2B17 enzymes in androgen metabolism and prostate cancer evolution.

    PubMed

    Gauthier-Landry, Louis; Bélanger, Alain; Barbier, Olivier

    2015-01-01

    In the prostate, approximately 50% of androgens are from adrenal steroids, mainly dehydroepiandrosterone (DHEA), its sulfate and androstenedione. These compounds are converted first into testosterone, and then into the active hormone dihydrotestosterone (DHT). After having activated the androgen receptor (AR), DHT is reduced into androstane-3α-DIOL (3α-DIOL) and androsterone (ADT), which are subsequently converted into 2 inactive and easily excretable metabolites: 3α-DIOL-17glucuronide (3α-DIOL-17G) and ADT-3glucuronide (ADT-3G). The formation of these last derivatives through the glucuronidation reaction involves 2 UDP-glucuronosyltransferase (UGT) enzymes, namely UGT2B15 and UGT2B17. The present review article aims at providing a comprehensive view of the physiological and pharmacological importance of these 2 enzymes for the control of androgen homeostasis. We will resume: (i) how UGT2B15 and UGT2B17 contribute to androgen elimination; (ii) how their glucuronidation capacity influences the androgen signaling pathway in prostate cells; (iii) how they contribute to the anti-proliferative properties of AR antagonists in prostate cancer cells; and (iv) how AR and its spliced variants regulate the UGT2B15 and/or UGT2B17 genes expression. Finally, whether the unexploited AR-UGT axis could serve as a prognostic maker or a pharmacological target for novel therapeutics in the treatment of prostate cancer is also discussed. This article is part of a special issue entitled 'Essential role of DHEA'. PMID:24861263

  8. Structure and expression of the gene (HNRPA2B1) encoding the human hnRNP protein A2/B1

    SciTech Connect

    Kozu, Tomoko; Henrich, B.; Schaefer, K.P.

    1995-01-20

    Heterogeneous nuclear ribonucleoprotein (hnRNP) A2 is a major nuclear protein and one of the major components of the hnRNP core complex in mammalian cells. We first determined the complete sequence of the human gene for hnRNP protein A2 (HNRPA2B1). The human HNRPA2B1 gene exists in a single copy over 9 kb in length. The gene was split into 12 exons, including a 36-nucleotide mini-exon, which was specific to the hnRNP protein B1, providing genetic evidence that the B1 mRNA was generated from the primary HNRPA2B1 transcript by alternative splicing. The 5{prime} region of HNRPA2B1 was GC-rich and contained several DNA motifs for the binding of several transcription factors, which included 2 CCAAT boxes and no TATA sequences. The 5{prime} ends of the mRNA were mapped to multiple positions. These structural features are characteristic of promoter regions of housekeeping genes. Northern blot and RT-PCR analyses of the HNRPA2B1 transcripts revealed levels of B1 mRNA from 2 to 5% of total A2/B1 transcripts and showed that both A2 and B1 mRNAs were transcribed in all human cell lines and mouse tissues studied. The structural and evolutionary characteristics of the A2 and A1 proteins as they relate to each other are discussed. 38 refs., 5 figs.

  9. Rap2b promotes proliferation, migration, and invasion of lung cancer cells.

    PubMed

    Peng, Yi-Gen; Zhang, Zheng-Qun; Chen, Yan-Bin; Huang, Jian-An

    2016-10-01

    Rap2b, a member of the guanosine triphosphate-binding proteins, is widely up-regulated in many types of tumors. However, the functional role of Rap2b in tumorigenesis of lung cancer remains to be fully elucidated. In this study, we investigated the effect of Rap2b on the lung cancer malignant phenotype, such as cell proliferation and metastasis. We found that Rap2b could promote the abilities of lung cancer cell wound healing, migration, and invasion via increasing matrix metalloproteinase-2 enzyme activity. Furthermore, Rap2b overexpression could increase the phosphorylation level of extracellular signal-regulated protein kinases 1/2. In conclusion, our results suggested that Rap2b may be a potential therapeutic target for lung cancer. PMID:26671640

  10. Genetic loss of SH2B3 in acute lymphoblastic leukemia

    PubMed Central

    Perez-Garcia, Arianne; Ambesi-Impiombato, Alberto; Hadler, Michael; Rigo, Isaura; LeDuc, Charles A.; Kelly, Kara; Jalas, Chaim; Paietta, Elisabeth; Racevskis, Janis; Rowe, Jacob M.; Tallman, Martin S.; Paganin, Maddalena; Basso, Giuseppe; Tong, Wei; Chung, Wendy K.

    2013-01-01

    The SH2B adaptor protein 3 (SH2B3) gene encodes a negative regulator of cytokine signaling with a critical role in the homeostasis of hematopoietic stem cells and lymphoid progenitors. Here, we report the identification of germline homozygous SH2B3 mutations in 2 siblings affected with developmental delay and autoimmunity, one in whom B-precursor acute lymphoblastic leukemia (ALL) developed. Mechanistically, loss of SH2B3 increases Janus kinase-signal transducer and activator of transcription signaling, promotes lymphoid cell proliferation, and accelerates leukemia development in a mouse model of NOTCH1-induced ALL. Moreover, extended mutation analysis showed homozygous somatic mutations in SH2B3 in 2 of 167 ALLs analyzed. Overall, these results demonstrate a Knudson tumor suppressor role for SH2B3 in the pathogenesis of ALL and highlight a possible link between genetic predisposition factors in the pathogenesis of autoimmunity and leukemogenesis. PMID:23908464

  11. Solution structure of the isolated histone H2A-H2B heterodimer

    PubMed Central

    Moriwaki, Yoshihito; Yamane, Tsutomu; Ohtomo, Hideaki; Ikeguchi, Mitsunori; Kurita, Jun-ichi; Sato, Masahiko; Nagadoi, Aritaka; Shimojo, Hideaki; Nishimura, Yoshifumi

    2016-01-01

    During chromatin-regulated processes, the histone H2A-H2B heterodimer functions dynamically in and out of the nucleosome. Although detailed crystal structures of nucleosomes have been established, that of the isolated full-length H2A-H2B heterodimer has remained elusive. Here, we have determined the solution structure of human H2A-H2B by NMR coupled with CS-Rosetta. H2A and H2B each contain a histone fold, comprising four α-helices and two β-strands (α1–β1–α2–β2–α3–αC), together with the long disordered N- and C-terminal H2A tails and the long N-terminal H2B tail. The N-terminal αN helix, C-terminal β3 strand, and 310 helix of H2A observed in the H2A-H2B nucleosome structure are disordered in isolated H2A-H2B. In addition, the H2A α1 and H2B αC helices are not well fixed in the heterodimer, and the H2A and H2B tails are not completely random coils. Comparison of hydrogen-deuterium exchange, fast hydrogen exchange, and {1H}-15N hetero-nuclear NOE data with the CS-Rosetta structure indicates that there is some conformation in the H2A 310 helical and H2B Lys11 regions, while the repression domain of H2B (residues 27–34) exhibits an extended string-like structure. This first structure of the isolated H2A-H2B heterodimer provides insight into its dynamic functions in chromatin. PMID:27181506

  12. HUMAN CYTOSOLIC SULFOTRANSFERASE 2B1: ISOFORM EXPRESSION, TISSUE SPECIFICITY AND SUBCELLULAR LOCALIZATION

    PubMed Central

    Falany, C.N.; He, D.; Dumas, N.; Frost, A.R.; Falany, J.L.

    2007-01-01

    Sulfation is an important Phase II conjugation reaction involved in the synthesis and metabolism of steroids in humans. Two different isoforms (2B1a and 2B1b) are encoded by the sulfotransferase (SULT) 2B1 gene utilizing different start sites of transcription resulting in the incorporation of different first exons. SULT2B1a and SULT2B1b are 350 and 365 amino acids in length, respectively, and the last 342 aa are identical. Message for both SULT2B1 isoforms is present in human tissues although SULT2B1b message is generally more abundant. However, to date only SULT2B1b protein has been detected in human tissues or cell lines. SULT2B1b is localized in the cytosol and/or nuclei of human cells. A unique 3′-extension of SULT2B1b is required for nuclear localization in human BeWo placental choriocarcinoma cells. Nuclear localization is stimulated by forskolin treatment in BeWo cells and serine phosphorylation has been identified in the 3′-extension. SULT2B1b is selective for the sulfation of 3β-hydroxysteroids such as dehydroepiandrosterone and pregnenolone, and may also have a role in cholesterol sulfation in human skin. The substrate specificity, nuclear localization, and tissue localization of SULT2B1b suggest a role in regulating the responsiveness of cells to adrenal androgens via their direct inactivation or by preventing their conversion to more potent androgens and estrogens. PMID:17055258

  13. Reduction and alkaline hydrolysis of 5-oxoindeno(1,2-b)pyridinium salts

    SciTech Connect

    Mutsenietse, D.Kh.; Zandersons, A.Z.; Lusis, V.K.; Dubur, G.Ya.

    1987-07-01

    5,9b-dihydro derivatives of indeno(1,2-b)pyridine were obtained by the reduction of the corresponding 1,2-dimethyl-4-acryl-5-oxoindeno(1,2-b)pyridinium perchlorates. 1,2-dimethyl-3-ethoxycarbonyl-4-phenyl-5-oxoindeno(1,2-b)pyridinium perchlorate forms in alkaline medium with splitting, recyclization and deamination products.

  14. Solution structure of the isolated histone H2A-H2B heterodimer.

    PubMed

    Moriwaki, Yoshihito; Yamane, Tsutomu; Ohtomo, Hideaki; Ikeguchi, Mitsunori; Kurita, Jun-Ichi; Sato, Masahiko; Nagadoi, Aritaka; Shimojo, Hideaki; Nishimura, Yoshifumi

    2016-01-01

    During chromatin-regulated processes, the histone H2A-H2B heterodimer functions dynamically in and out of the nucleosome. Although detailed crystal structures of nucleosomes have been established, that of the isolated full-length H2A-H2B heterodimer has remained elusive. Here, we have determined the solution structure of human H2A-H2B by NMR coupled with CS-Rosetta. H2A and H2B each contain a histone fold, comprising four α-helices and two β-strands (α1-β1-α2-β2-α3-αC), together with the long disordered N- and C-terminal H2A tails and the long N-terminal H2B tail. The N-terminal αN helix, C-terminal β3 strand, and 310 helix of H2A observed in the H2A-H2B nucleosome structure are disordered in isolated H2A-H2B. In addition, the H2A α1 and H2B αC helices are not well fixed in the heterodimer, and the H2A and H2B tails are not completely random coils. Comparison of hydrogen-deuterium exchange, fast hydrogen exchange, and {(1)H}-(15)N hetero-nuclear NOE data with the CS-Rosetta structure indicates that there is some conformation in the H2A 310 helical and H2B Lys11 regions, while the repression domain of H2B (residues 27-34) exhibits an extended string-like structure. This first structure of the isolated H2A-H2B heterodimer provides insight into its dynamic functions in chromatin. PMID:27181506

  15. Characterization of acetylation of Saccharomyces cerevisiae H2B by mass spectrometry

    NASA Astrophysics Data System (ADS)

    Zhang, Kangling

    2008-11-01

    Following the identification of histone H3 modifications in Saccharomyces cerevisiae [K. Zhang, Int. J. Mass Spectrom. 269 (2008) 101-111], here, we report a detailed characterization of post-translational modifications by LC/MS/MS analysis of tryptic and Glu-C digests of H2B proteins isolated from S. cerevisiae. We show that both H2B.1 and H2B.2 are acetylated at K6, K11, K16, K21 and K22 while H2B.2 has an additional acetylation site at K3. All the acetylation sites of yeast H2B except K3 of H2B.2 are located at the same positions on aligned protein sequences of Arabidopsis H2B variants that were reported previously to be acetylated at K6, K11, K27, K32, K38 and K39. A unique acetylation motif AEK is observed in the H2B variants of these two species, indicating a plant/yeast H2B specific acetyltransferase may exist.

  16. Mechanism-Based Inactivation of Human Cytochrome P450 2B6 by Chlorpyrifos.

    PubMed

    D'Agostino, Jaime; Zhang, Haoming; Kenaan, Cesar; Hollenberg, Paul F

    2015-07-20

    Chlorpyrifos (CPS) is a commonly used pesticide which is metabolized by P450s into the toxic metabolite chlorpyrifos-oxon (CPO). Metabolism also results in the release of sulfur, which has been suggested to be involved in mechanism-based inactivation (MBI) of P450s. CYP2B6 was previously determined to have the greatest catalytic efficiency for CPO formation in vitro. Therefore, we characterized the MBI of CYP2B6 by CPS. CPS inactivated CYP2B6 in a time- and concentration-dependent manner with a kinact of 1.97 min(-1), a KI of 0.47 μM, and a partition ratio of 17.7. We further evaluated the ability of other organophosphate pesticides including chorpyrifos-methyl, diazinon, parathion-methyl, and azinophos-methyl to inactivate CYP2B6. These organophosphate pesticides were also potent MBIs of CYP2B6 characterized by similar kinact and KI values. The inactivation of CYP2B6 by CPS was accompanied by the loss of P450 detectable in the CO reduced spectrum and loss of detectable heme. High molecular weight aggregates were observed when inactivated CYP2B6 was run on SDS-PAGE gels indicating protein aggregation. Interestingly, we found that the rat homologue of CYP2B6, CYP2B1, was not inactivated by CPS despite forming CPO to a similar extent. On the basis of the locations of the Cys residues in the two proteins which could react with released sulfur during the metabolism of CPS, we investigated whether the C475 in CYP2B6, which is not conserved in CYP2B1, was the critical residue for inactivation by mutating it to a Ser. CYP2B6 C475S was inactivated to a similar extent as wild type CYP2B6 indicating that C475 is not likely the key difference between CYP2B1 and CYP2B6 with respect to inactivation. These results indicate that CPS and other organophosphate pesticides are potent MBIs of CYP2B6 which may have implications for the toxicity of these pesticides as well as the potential for pesticide-drug interactions. PMID:26075493

  17. Physik gestern und heute Das Eiskalorimeter

    NASA Astrophysics Data System (ADS)

    Heering, P.

    2003-07-01

    Kalorimetrische Messungen gehören heute zum experimentellen Standardrepertoire im Bereich der Thermodynamik und der physikalischen Chemie. Das erste Gerät für derartige Messungen entwickelten Ende des 18. Jahrhunderts die französischen Wissenschaftler Antoine Laurent Lavoisier und Pierre Simon de Laplace.

  18. Field production and functional evaluation of chloroplast-derived interferon-α2b

    PubMed Central

    Arlen, Philip A.; Falconer, Regina; Cherukumilli, Sri; Cole, Amy; Cole, Alexander M.; Oishi, Karen K.; Daniell, Henry

    2008-01-01

    Summary Type I interferons (IFNs) inhibit viral replication and cell growth and enhance the immune response, and therefore have many clinical applications. IFN-α2b ranks third in world market use for a biopharmaceutical, behind only insulin and erythropoietin. The average annual cost of IFN-α2b for the treatment of hepatitis C infection is $26 000, and is therefore unavailable to the majority of patients in developing countries. Therefore, we expressed IFN-α2b in tobacco chloroplasts, and transgenic lines were grown in the field after obtaining United States Department of Agriculture Animal and Plant Health Inspection Service (USDA-APHIS) approval. Stable, site-specific integration of transgenes into chloroplast genomes and homoplasmy through several generations were confirmed. IFN-α2b levels reached up to 20% of total soluble protein, or 3 mg per gram of leaf (fresh weight). Transgenic IFN-α2b had similar in vitro biological activity to commercially produced PEG-Intron™ when tested for its ability to protect cells against cytopathic viral replication in the vesicular stomatitis virus cytopathic effect (VSV CPE) assay and to inhibit early-stage human immunodeficiency virus (HIV) infection. The antitumour and immunomodulating properties of IFN-α2b were also seen in vivo . Chloroplast-derived IFN-α2b increased the expression of major histocompatibility complex class I (MHC I) on splenocytes and the total number of natural killer (NK) cells. Finally, IFN-α2b purified from chloroplast transgenic lines (cpIFN-α2b) protected mice from a highly metastatic tumour line. This demonstration of high levels of expression of IFN-α2b, transgene containment and biological activity akin to that of commercial preparations of IFN-α2b facilitated the first field production of a plant-derived human blood protein, a critical step towards human clinical trials and commercialization. PMID:17490449

  19. Phosphorylation-dependent changes in nucleotide binding, conformation, and dynamics of the first nucleotide binding domain (NBD1) of the sulfonylurea receptor 2B (SUR2B).

    PubMed

    de Araujo, Elvin D; Alvarez, Claudia P; López-Alonso, Jorge P; Sooklal, Clarissa R; Stagljar, Marijana; Kanelis, Voula

    2015-09-11

    The sulfonylurea receptor 2B (SUR2B) forms the regulatory subunit of ATP-sensitive potassium (KATP) channels in vascular smooth muscle. Phosphorylation of the SUR2B nucleotide binding domains (NBD1 and NBD2) by protein kinase A results in increased channel open probability. Here, we investigate the effects of phosphorylation on the structure and nucleotide binding properties of NBD1. Phosphorylation sites in SUR2B NBD1 are located in an N-terminal tail that is disordered. Nuclear magnetic resonance (NMR) data indicate that phosphorylation of the N-terminal tail affects multiple residues in NBD1, including residues in the NBD2-binding site, and results in altered conformation and dynamics of NBD1. NMR spectra of NBD1 lacking the N-terminal tail, NBD1-ΔN, suggest that phosphorylation disrupts interactions of the N-terminal tail with the core of NBD1, a model supported by dynamic light scattering. Increased nucleotide binding of phosphorylated NBD1 and NBD1-ΔN, compared with non-phosphorylated NBD1, suggests that by disrupting the interaction of the NBD core with the N-terminal tail, phosphorylation also exposes the MgATP-binding site on NBD1. These data provide insights into the molecular basis by which phosphorylation of SUR2B NBD1 activates KATP channels. PMID:26198630

  20. 50 CFR Table 2b to Part 679 - Species Codes: FMP Prohibited Species and CR Crab

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 50 Wildlife and Fisheries 11 2011-10-01 2011-10-01 false Species Codes: FMP Prohibited Species and CR Crab 2b Table 2b to Part 679 Wildlife and Fisheries FISHERY CONSERVATION AND MANAGEMENT, NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE (CONTINUED) FISHERIES OF THE EXCLUSIVE ECONOMIC ZONE OFF ALASKA Pt. 679, Table...

  1. A Decompositional Approach to Executing Quality Data Model Algorithms on the i2b2 Platform.

    PubMed

    Mo, Huan; Jiang, Guoqian; Pacheco, Jennifer A; Kiefer, Richard; Rasmussen, Luke V; Pathak, Jyotishman; Denny, Joshua C; Thompson, William K

    2016-01-01

    The Quality Data Model (QDM) is an established standard for representing electronic clinical quality measures on electronic health record (EHR) repositories. The Informatics for Integrated Biology and the Bedside (i2b2) is a widely used platform for implementing clinical data repositories. However, translation from QDM to i2b2 is challenging, since QDM allows for complex queries beyond the capability of single i2b2 messages. We have developed an approach to decompose complex QDM algorithms into workflows of single i2b2 messages, and execute them on the KNIME data analytics platform. Each workflow operation module is composed of parameter lists, a template for the i2b2 message, an mechanism to create parameter updates, and a web service call to i2b2. The communication between workflow modules relies on passing keys ofi2b2 result sets. As a demonstration of validity, we describe the implementation and execution of a type 2 diabetes mellitus phenotype algorithm against an i2b2 data repository. PMID:27570665

  2. SRC Inhibition Reduces NR2B Surface Expression and Synaptic Plasticity in the Amygdala

    ERIC Educational Resources Information Center

    Sinai, Laleh; Duffy, Steven; Roder, John C.

    2010-01-01

    The Src protein tyrosine kinase plays a central role in the regulation of N-methyl-d-aspartate receptor (NMDAR) activity by regulating NMDAR subunit 2B (NR2B) surface expression. In the amygdala, NMDA-dependent synaptic plasticity resulting from convergent somatosensory and auditory inputs contributes to emotional memory; however, the role of Src…

  3. Fabrication Report for the AFC-2A and AFC-2B Capsule Irradiations in the ATR

    SciTech Connect

    Timothy A. Hyde

    2007-10-01

    This document provides a general narrative description of the AFC-2A and 2B fuel fabrication processes for the AFC 2A and AFC 2B fuel irradiation experiments fabricated at the Idaho National Laboratory’s Materials and Fuels Complex (MFC) for irradiation in the Advanced Test Reactor (ATR).

  4. Pathogenesis of PCV2a and PCV2b virus in germ-free pigs

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Genetic analysis of porcine circovirus type 2 (PCV2) reveals 2 subgroups that will be referred to as PCV2a and PCV2b representing the North American and European prototypes respectfully. This paper summarizes 3 studies comparing the pathogenesis of 2a and 2b viruses in germ-free pigs. In this PCV2...

  5. First identification of Porcine Circovirus Type 2b mutant in pigs from Uruguay.

    PubMed

    Ramos, Natalia; Mirazo, Santiago; Castro, Gustavo; Arbiza, Juan

    2015-07-01

    Porcine Circovirus Type 2 (PCV2) is a worldwide distributed virus and is considered an important emerging pathogen related to several distinct disease syndromes in pigs. PCV2 strains are classified into three genotypes: PCV2a, with five subtypes (2A-2E), PCV2b with three subtypes (1A-1C) and PCV2c, only found in Denmark. Recently, several reports suggested the circulation of newly emerging PCV2b mutants (mPCV2b) isolated from pigs with PCVAD in cases of suspected vaccine failure. In this work, we report for the first time the identification of mPCV2b in pigs from Uruguay, providing an additional evidence of a global circulation. Complete genome characterization and phylogenetic analysis reveal that Uruguayan strains, as well as mPCV2b previously reported are closely related to other sequences already classified as PCV2b-1C. Furthermore, results showed that mPCV2b presented different genetic markers in the capsid protein compared with classical PCV2a/b strains. Further investigation about antigenic shift of the mPCV2b strains including the Uruguayan isolates is needed. PMID:26004195

  6. 50 CFR Table 2b to Part 679 - Species Codes: FMP Prohibited Species and CR Crab

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... CR Crab 2b Table 2b to Part 679 Wildlife and Fisheries FISHERY CONSERVATION AND MANAGEMENT, NATIONAL... CR Crab Species Description Code CR Crab Groundfish PSC CRAB Box Lopholithodes mandtii 900 ✓ Dungeness Cancer magister 910 ✓ King, blue Paralithodes platypus 922 ✓ ✓ King, golden (brown)...

  7. 50 CFR Table 2b to Part 679 - Species Codes: FMP Prohibited Species and CR Crab

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 50 Wildlife and Fisheries 13 2012-10-01 2012-10-01 false Species Codes: FMP Prohibited Species and CR Crab 2b Table 2b to Part 679 Wildlife and Fisheries FISHERY CONSERVATION AND MANAGEMENT, NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE (CONTINUED) FISHERIES OF THE EXCLUSIVE ECONOMIC ZONE OFF ALASKA Pt. 679, Table...

  8. 50 CFR Table 2b to Part 679 - Species Codes: FMP Prohibited Species and CR Crab

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... CR Crab 2b Table 2b to Part 679 Wildlife and Fisheries FISHERY CONSERVATION AND MANAGEMENT, NATIONAL... CR Crab Species Description Code CR Crab Groundfish PSC CRAB Box Lopholithodes mandtii 900 ✓ Dungeness Cancer magister 910 ✓ King, blue Paralithodes platypus 922 ✓ ✓ King, golden (brown)...

  9. A Decompositional Approach to Executing Quality Data Model Algorithms on the i2b2 Platform

    PubMed Central

    Mo, Huan; Jiang, Guoqian; Pacheco, Jennifer A.; Kiefer, Richard; Rasmussen, Luke V.; Pathak, Jyotishman; Denny, Joshua C.; Thompson, William K.

    2016-01-01

    The Quality Data Model (QDM) is an established standard for representing electronic clinical quality measures on electronic health record (EHR) repositories. The Informatics for Integrated Biology and the Bedside (i2b2) is a widely used platform for implementing clinical data repositories. However, translation from QDM to i2b2 is challenging, since QDM allows for complex queries beyond the capability of single i2b2 messages. We have developed an approach to decompose complex QDM algorithms into workflows of single i2b2 messages, and execute them on the KNIME data analytics platform. Each workflow operation module is composed of parameter lists, a template for the i2b2 message, an mechanism to create parameter updates, and a web service call to i2b2. The communication between workflow modules relies on passing keys ofi2b2 result sets. As a demonstration of validity, we describe the implementation and execution of a type 2 diabetes mellitus phenotype algorithm against an i2b2 data repository. PMID:27570665

  10. Noncanonical sortase-mediated assembly of pilus type 2b in group B Streptococcus.

    PubMed

    Lazzarin, Maddalena; Cozzi, Roberta; Malito, Enrico; Martinelli, Manuele; D'Onofrio, Mariapina; Maione, Domenico; Margarit, Immaculada; Rinaudo, C Daniela

    2015-11-01

    Group B Streptococcus (GBS) expresses 3 structurally distinct pilus types (1, 2a, and 2b) identified as important virulence factors and vaccine targets. These pili are heterotrimeric polymers, covalently assembled on the cell wall by sortase (Srt) enzymes. We investigated the pilus-2b biogenesis mechanism by using a multidisciplinary approach integrating genetic, biochemical, and structural studies to dissect the role of the 2 pilus-2b-associated Srts. We show that only 1 sortase (SrtC1-2b) is responsible for pilus protein polymerization, whereas the second one (Srt2-2b) does not act as a pilin polymerase, but similarly to the housekeeping class A Srt (SrtA), it is involved in cell-wall pilus anchoring by targeting the minor ancillary subunit. Based on its function and sequence features, Srt2-2b does not belong to class C Srts (SrtCs), nor is it a canonical member of any other known family of Srts. We also report the crystal structure of SrtC1-2b at 1.9 Å resolution. The overall fold resembles the typical structure of SrtCs except for the N-terminal lid region that appears in an open conformation displaced from the active site. Our findings reveal that GBS pilus type 2b biogenesis differs significantly from the current model of pilus assembly in gram-positive pathogens. PMID:26202865

  11. A2B adenosine receptor activity is reduced in neutrophils from patients with systemic sclerosis

    PubMed Central

    Bazzichi, Laura; Trincavelli, Letizia; Rossi, Alessandra; De Feo, Francesca; Lucacchini, Antonio; Bombardieri, Stefano; Martini, Claudia

    2005-01-01

    We conducted the present study to investigate protein expression and functioning of A2A and A2B adenosine receptors (ARs) in neutrophils of patients affected by systemic sclerosis (SSc). The presence of A2A and A2B ARs was assessed by immunoblotting using specific antibodies. Equilibrium A2A and A2B ARs binding parameters were evaluated by radioligand binding assay. Functional studies were conducted to investigate coupling of the A2B AR to the adenylyl cyclase pathway. This is the first report of the use of Western blot analysis to confirm the presence of A2A and A2B ARs in human neutrophils. No significant changes in A2A AR binding parameters or expression levels were detected between SSc patients and healthy control individuals. A significant decrease (65%) in the maximum density of A2B AR binding sites occurred in SSc neutrophils, whereas no changes in the affinity constant values were found. Moreover, a decrease in A2B AR mediated adenylyl cyclase activity was observed in patients with SSc. Our findings demonstrate the occurrence of selective alterations in A2B AR density and signalling in SSc. PMID:15743465

  12. Rap2B promotes cell proliferation, migration and invasion in prostate cancer.

    PubMed

    Di, Jiehui; Cao, Huan; Tang, Juangjuan; Lu, Zheng; Gao, Keyu; Zhu, Zhesi; Zheng, Junnian

    2016-06-01

    Rap2B, a member of the Ras family of small GTP-binding proteins, reportedly presents a high level of expression in various human tumors and plays a significant role in the development of tumor. However, the function of Rap2B in prostate cancer (PCa) remains unclear. We elucidated the stimulative role of Rap2B in PCa cell proliferation, migration and invasion by means of the CCK-8 cell proliferation assay, cell cycle analysis and transwell migration assay. Western blot analysis uncovered that elevated Rap2B leads to increased phosphorylation levels of FAK, suggesting that FAK-dependent pathway might be responsible for the effect of Rap2B on PCa cells migration and invasion. Inversely, FAK-specific inhibitor (PF-573228) can abort Rap2B-induced FAK phosphorylation. In vivo experiment confirmed that Rap2B positively regulated PCa growth and metastasis, as well as the expression of phosphorylated FAK. Collectively, these findings shed light on Rap2B as a potential therapeutic target for PCa. PMID:27154636

  13. Mikro- und Nanokapseln aus Funktionspolymeren, Biopolymeren und Proteinen

    NASA Astrophysics Data System (ADS)

    Schüler, Corinna

    2001-03-01

    In dieser Arbeit wird die Beschichtung von kolloidalen Templaten mit Hilfe der Layer-by-layer Technik beschrieben. Mit ihr ist es möglich, die Oberfläche der Template mit sehr dünnen und gut definierten Filmen zu versehen. Durch Auflösung der Template werden Kapseln hergestellt, die je nach Zusammensetzung der Beschichtung unterschiedliche Eigenschaften aufweisen. In this thesis the coating of colloid templates using the layer-by-layer technique is described. The surface of the templates is modified with thin, well defined films. After dissolving the templates, hollow capsules with different properties are obtained.

  14. Synaptotagmin-1 C2B domain interacts simultaneously with SNAREs and membranes to promote membrane fusion

    PubMed Central

    Wang, Shen; Li, Yun; Ma, Cong

    2016-01-01

    Synaptotagmin-1 (Syt1) acts as a Ca2+ sensor for neurotransmitter release through its C2 domains. It has been proposed that Syt1 promotes SNARE-dependent fusion mainly through its C2B domain, but the underlying mechanism is poorly understood. In this study, we show that the C2B domain interacts simultaneously with acidic membranes and SNARE complexes via the top Ca2+-binding loops, the side polybasic patch, and the bottom face in response to Ca2+. Disruption of the simultaneous interactions completely abrogates the triggering activity of the C2B domain in liposome fusion. We hypothesize that the simultaneous interactions endow the C2B domain with an ability to deform local membranes, and this membrane-deformation activity might underlie the functional significance of the Syt1 C2B domain in vivo. DOI: http://dx.doi.org/10.7554/eLife.14211.001 PMID:27083046

  15. i2b2t2: Unlocking Visualization for Clinical Research.

    PubMed

    Harris, Daniel R; Henderson, Darren W

    2016-01-01

    We introduce a tool that extracts clinical data sets and provides visualizations from clinical data warehouses that use the Informatics for Integrating Biology and the Bedside (i2b2) query tool. Our tool, i2b2t2 (i2b2 to Tableau), can extract and visualize any i2b2 query into a portable format that researchers can easily explore without needing a highly technical or statistical background. This user-friendly format provides a quick visual summary of the queried population and is easily extendable to develop more intricate and robust visualizations. Extraction and visualization can be provided as a service by clinical data warehouses to expedite the release of data sets for research. i2b2t2 also encourages visualization as a self-service; a motivated researcher can develop custom visualizations for exploration or publication. PMID:27570658

  16. i2b2t2: Unlocking Visualization for Clinical Research

    PubMed Central

    Harris, Daniel R.; Henderson, Darren W.

    2016-01-01

    We introduce a tool that extracts clinical data sets and provides visualizations from clinical data warehouses that use the Informatics for Integrating Biology and the Bedside (i2b2) query tool. Our tool, i2b2t2 (i2b2 to Tableau), can extract and visualize any i2b2 query into a portable format that researchers can easily explore without needing a highly technical or statistical background. This user-friendly format provides a quick visual summary of the queried population and is easily extendable to develop more intricate and robust visualizations. Extraction and visualization can be provided as a service by clinical data warehouses to expedite the release of data sets for research. i2b2t2 also encourages visualization as a self-service; a motivated researcher can develop custom visualizations for exploration or publication. PMID:27570658

  17. Synaptotagmin-1 C2B domain interacts simultaneously with SNAREs and membranes to promote membrane fusion.

    PubMed

    Wang, Shen; Li, Yun; Ma, Cong

    2016-01-01

    Synaptotagmin-1 (Syt1) acts as a Ca(2+) sensor for neurotransmitter release through its C2 domains. It has been proposed that Syt1 promotes SNARE-dependent fusion mainly through its C2B domain, but the underlying mechanism is poorly understood. In this study, we show that the C2B domain interacts simultaneously with acidic membranes and SNARE complexes via the top Ca(2+)-binding loops, the side polybasic patch, and the bottom face in response to Ca(2+). Disruption of the simultaneous interactions completely abrogates the triggering activity of the C2B domain in liposome fusion. We hypothesize that the simultaneous interactions endow the C2B domain with an ability to deform local membranes, and this membrane-deformation activity might underlie the functional significance of the Syt1 C2B domain in vivo. PMID:27083046

  18. Inactivation of purified rat liver cytochrome P-450 2B1 and rabbit liver cytochrome P-450 2B4 by N-methylcarbazole.

    PubMed

    Kuemmerle, S C; Shen, T; Hollenberg, P F

    1994-01-01

    Metabolism of N-methylcarbazole by purified rat liver cytochrome P-450 2B1 or rabbit liver P-450 2B4 resulted in the inactivation of these enzymes in a time-dependent, pseudo-first order manner as assayed spectrally by the decrease in the reduced CO spectrum at 450 nm. The inactivation was saturable with respect to the concentration of N-methylcarbazole, and a Ki = 5.2 microM and kINACT = 0.14 min-1 were determined for the inactivation of P-450 2B1. For P-450 2B4 inactivation, the Ki was 23 microM and the kINACT = 0.21 min-1. There was no increase in the reduced CO spectrum at 420 nm accompanying the inactivation, and the slight loss of the P-450 heme prosthetic group, as determined by the spectrum at 418 nm, was not sufficient to account for the loss of the reduced CO spectrum at 450 nm. The metabolism of N-methylcarbazole by P-450 did not result in the formation of a metabolic intermediate complex, which could also be responsible for the loss of cytochrome P-450 activity. Loss of catalytic activity for further substrate metabolism was also observed after preincubation of enzyme with N-methylcarbazole and the loss of catalytic activity correlated with the loss of the reduced CO spectrum. Accompanying the loss of spectrally detectable P-450 2B1 and P-450 2B4 catalytic activity, there was an increase in the NADPH oxidation rate. This increased rate persisted on subsequent addition of NADPH. PMID:8070309

  19. Enhancing photoactivity of TiO2(B)/anatase core-shell nanofibers by selectively doping cerium ions into the TiO2(B) core.

    PubMed

    Yang, Dongjiang; Zhao, Jian; Liu, Hongwei; Zheng, Zhanfeng; Adebajo, Moses O; Wang, Hongxia; Liu, Xiaotang; Zhang, Hongjie; Zhao, Jin-cai; Bell, John; Zhu, Huaiyong

    2013-04-15

    Cerium ions (Ce(3+)) can be selectively doped into the TiO2(B) core of TiO2(B)/anatase core-shell nanofibers by means of a simple one-pot hydrothermal treatment of a starting material of hydrogen trititanate (H2Ti3O7) nanofibers. These Ce(3+) ions (≈0.202 nm) are located on the (110) lattice planes of the TiO2(B) core in tunnels (width≈0.297 nm). The introduction of Ce(3+) ions reduces the defects of the TiO2(B) core by inhibiting the faster growth of (110) lattice planes. More importantly, the redox potential of the Ce(3+)/Ce(4+) couple (E°(Ce(3+)/Ce(4+))=1.715 V versus the normal hydrogen electrode) is more negative than the valence band of TiO2(B). Therefore, once the Ce(3+)-doped nanofibers are irradiated by UV light, the doped Ce(3+) ions--in close vicinity to the interface between the TiO2(B) core and anatase nanoshell--can efficiently trap the photogenerated holes. This facilitates the migration of holes from the anatase shell and leaves more photogenerated electrons in the anatase nanoshell, which results in a highly efficient separation of photogenerated charges in the anatase nanoshell. Hence, this enhanced charge-separation mechanism accelerates dye degradation and alcohol oxidation processes. The one-pot treatment doping strategy is also used to selectively dope other metal ions with variable oxidation states such as Co(2+/3+) and Cu(+/2+) ions. The doping substantially improves the photocatalytic activity of the mixed-phase nanofibers. In contrast, the doping of ions with an invariable oxidation state, such as Zn(2+), Ca(2+), or Mg(2+), does not enhance the photoactivity of the mixed-phase nanofibers as the ions could not trap the photogenerated holes. PMID:23417892

  20. Arbidol exhibits strong inhibition towards UDP-glucuronosyltransferase (UGT) 1A9 and 2B7.

    PubMed

    Liu, Xin; Huang, Ting; Chen, Jian-Xing; Zeng, Jia; Fan, Xu-Ran; Xu-Zhu; Yu, Zhen-Wen; Sun, Xiao-Yu; Hong, Mo; Sun, Hong-Zhi

    2013-12-01

    The aim of the present study was to investigate arbidol's inhibition towards UDP-glucuronosyltransferase (UGT) 1A9 and 2B7. The nonspecific probe substrate 4-methylumbelliferone (4-MU) and recombinant UGT enzymes (UGT1A9, UGT2B7) were firstly used to evaluate the inhibition of arbidol towards UGT1A9 and UGT2B7. Furthermore, specific substrates of UGT1A9 and UGT2B7 propofol and zidovudine (AZT) were used to determine the inhibition of arbidol towards UGT1A9 and UGT2B7. Inhibition type and inhibition kinetic parameters (Ki) were determined. In vitro-in vivo extrapolation (IV-IVE) was performed to predict in vivo DDI magnitude induced by arbidol. Arbidol was demonstrated to exhibit competitive inhibition towards UGT1A9 and UGT2B7 without substate-dependent behaviour. The inhibition kinetic parameters (Ki) were calculated to be 0.5 microM, 3.5 microM, 2.8 microM, 29.7 microM for UGT2B7-mediated 4-MU glucuronidation, UGT1A9-mediated 4-MU glucuronidation, UGT2B7-mediated AZT glucuronidation, and UGT1A9-mediated propofol glucuronidation, respectively. Using these parameters, the in vivo alteration of area under of concentration-time curve (AUC) was calculated to be 156%, 22%, 28% and 2.6%, respectively. Given that arbidol exhibits strong inhibition towards UGT1A9 and UGT2B7, clinical monitoring should be given when arbidol was co-administered with drugs mainly undergoing UGT1A9, UGT2B7-mediated metabolism. PMID:24400440

  1. Cloning and expression of a rat brain. alpha. sub 2B -adrenergic receptor

    SciTech Connect

    Flordellis, C.S.; Handy, D.E.; Bresnahan, M.R.; Zannis, V.I.; Gavras, H. )

    1991-02-01

    The authors isolated a cDNA clone (RB{alpha}{sub 2B}) and its homologous gene (GR{alpha}{sub 2B}) encoding an {alpha}{sub 2B}-adrenergic receptor subtype by screening a rat brain cDNA and a rat genomic library. Nucleotide sequence analysis showed that both clones code for a protein of 458 amino acids, which is 87% homologous to the human kidney glycosylated adrenergic receptor ({alpha}{sub 2}-C4) and divergent from the rat kidney nonglycosylated {alpha}{sub 2B} subtype (RNG{alpha}{sub 2}). Transient expression of RB{alpha}{sub 2B} in COS-7 cells resulted in high-affinity saturable binding for ({sup 3}H)rauwolscine and a high receptor number in the membranes of transfected COS-7 cells. Pharmacological analysis demonstrated that the expressed receptor bound adrenergic ligands with the following order of potency: rauwolscine {gt} yohimbine {gt} prazosin {gt} oxymetazoline, with a prazosin-to-oxymetazoline K{sub i} ratio of 0.34. This profile is characteristic of the {alpha}{sub 2B}-adrenergic receptor subtype. Blotting analysis of rat brain mRNA gave one major and two minor mRNA species, and hybridization with strand-specific probes showed that both DNA strands of GR{alpha}{sub 2B} may be transcriptionally active. These findings show that rat brain expresses an {alpha}{sub 2B}-adrenergic receptor subtype that is structurally different from the rat kidney nonglycosylated {alpha}{sub 2B} subtype. Thus the rat expresses at least two divergent {alpha}{sub 2B}-adrenergic receptors.

  2. Immunogold localization of tobravirus 2b nematode transmission helper protein associated with virus particles.

    PubMed

    Vellios, Evangelos; Duncan, George; Brown, Derek; MacFarlane, Stuart

    2002-08-15

    Transmission of the tobraviruses Tobacco rattle virus (TRV) and Pea early-browning virus (PEBV) by trichodorid vector nematodes requires the viral coat protein (CP) and the 2b protein, a nonstructural protein encoded by RNA2, the smaller of the two viral genomic RNAs. It is hypothesized that the 2b protein functions by interacting with a small, flexible domain located at the C-terminus of the CP, forming a bridge between the virus particle and the internal surface of the vector nematode feeding apparatus. Antibodies specific for the 2b protein of PEBV or TRV did not bind to virus particles that were adsorbed to electron microscope grids and were not able to trap virus particles from extracts of infected plants. However, electron microscopy of thin sections of plants infected with PEBV probed with 2b-specific antibodies which were further gold-labeled showed that the 2b protein localizes exclusively to virus particles. Similarly, immunogold localization studies showed that the 2b protein of TRV isolate PaY4 is associated only with TRV PaY4 virus particles. When a recombinant TRV encoding the PaY4 2b protein and the CP from TRV isolate PpK20 was examined, the 2b protein could not be detected by Western blotting and in IGL experiments was not associated with virus particles. These results suggest that in the absence of a specific interaction between compatible CP and 2b proteins, the 2b protein does not accumulate. PMID:12202212

  3. The potential role of myocardial serotonin receptor 2B expression in canine dilated cardiomyopathy.

    PubMed

    Fonfara, Sonja; Hetzel, Udo; Oyama, Mark A; Kipar, Anja

    2014-03-01

    Serotonin signalling in the heart is mediated by receptor subtype 2B (5-HTR2B). A contribution of serotonin to valvular disease has been reported, but myocardial expression of 5-HTR2B and its role in canine dilated cardiomyopathy (DCM) is not known. The aim of the present study was to investigate myocardial 5-HTR2B mRNA expression in dogs with DCM and to correlate results with expression of markers for inflammation and remodelling. Myocardial samples from eight healthy dogs, four dogs with DCM, five with cardiac diseases other than DCM and six with systemic non-cardiac diseases were investigated for 5-HTR2B mRNA expression using quantitative PCR (qPCR). The results were compared to mRNA expression of selected cytokines, matrix metalloproteinases (MMP) and tissue inhibitors of matrix metalloproteinase (TIMP). Laser microdissection with subsequent qPCR and immunohistochemistry were employed to identify the cells expressing 5-HTR2B. The myocardium of control dogs showed constitutive 5-HTR2B mRNA expression. In dogs with DCM, 5-HTR2B mRNA values were significantly greater than in all other groups, with highest levels of expression in the left ventricle and right atrium. Myocytes were identified as the source of 5-HTR2B mRNA and protein. A significant positive correlation of 5-HTR2B mRNA with expression of several cytokines, MMPs and TIMPs was observed. The findings suggest that serotonin might play a role in normal cardiac structure and function and could contribute to myocardial remodelling and functional impairment in dogs with DCM. PMID:24440442

  4. Ribonucleotide reductase small subunit M2B prognoses better survival in colorectal cancer

    PubMed Central

    Liu, Xiyong; Lai, Lily; Wang, Xiaochen; Xue, Lijun; Leora, Sofia; Wu, Jun; Hu, Shuya; Zhang, Keqiang; Kuo, Mei-Ling; Zhou, Lun; Zhang, Hang; Wang, Yafan; Wang, Yan; Zhou, Bingsen; Nelson, Rebecca A; Zheng, Shu; Zhang, Suzhan; Chu, Peiguo; Yen, Yun

    2011-01-01

    Ribonucleotide reductase subunit RRM2B (p53R2) has been reported to suppress invasion and metastasis in colorectal cancer (CRC). Here we report that high levels of RRM2B expression is correlated with markedly better survival in CRC patients. In a fluorescence-labeled orthotopic mouse xenograft model, we confirmed that overexpression of RRM2B in non-metastatic CRC cells prevented lung and/or liver metastasis, relative to control cells that did metastasize. Clinical outcome studies were conducted on a training set with 103 CRCs and a validation set with 220 CRCs. All participants underwent surgery with periodic follow-up to determine survivability. A newly developed specific RRM2B antibody was employed to perform immunohistochemistry (IHC) for determining RRM2B expression levels on tissue arrays. In the training set, the Kaplan-Meier and multivariate COX analysis revealed that RRM2B is associated with better survival of CRCs, especially in stage IV patients (Hazard ratio, HR=0.40; 95% CI 0.18–0.86, p=0.016). In the validation set, RRM2B was negatively related to tumor invasion (odds ratio, OR=0.45, 95% CI 0.19–0.99, p=0.040) and lymph node involvement (OR=0.48, 95% CI 0.25–0.92, p=0.026). Further, elevated expression of RRM2B was associated with better prognosis in this set as determined by multivariate analyses (HR=0.48, 95% CI 0.26–0.91, p=0.030). Further investigations revealed that RRM2B was correlated with better survival of CRCs with advanced stage III–IV tumors rather than earlier stage I–II tumors. Taken together, our findings establish that RRM2B suppresses invasiveness of cancer cells and that its expression is associated with a better survival prognosis for CRC patients. PMID:21415168

  5. Expression, purification, and crystallization of Schizosaccharomyces pombe eIF2B.

    PubMed

    Kashiwagi, Kazuhiro; Shigeta, Tomoaki; Imataka, Hiroaki; Ito, Takuhiro; Yokoyama, Shigeyuki

    2016-03-01

    Tight control of protein synthesis is necessary for cells to respond and adapt to environmental changes rapidly. Eukaryotic translation initiation factor (eIF) 2B, the guanine nucleotide exchange factor for eIF2, is a key target of translation control at the initiation step. The nucleotide exchange activity of eIF2B is inhibited by the stress-induced phosphorylation of eIF2. As a result, the level of active GTP-bound eIF2 is lowered, and protein synthesis is attenuated. eIF2B is a large multi-subunit complex composed of five different subunits, and all five of the subunits are the gene products responsible for the neurodegenerative disease, leukoencephalopathy with vanishing white matter. However, the overall structure of eIF2B has remained unresolved, due to the difficulty in preparing a sufficient amount of the eIF2B complex. To overcome this problem, we established the recombinant expression and purification method for eIF2B from the fission yeast Schizosaccharomyces pombe. All five of the eIF2B subunits were co-expressed and reconstructed into the complex in Escherichia coli cells. The complex was successfully purified with a high yield. This recombinant eIF2B complex contains each subunit in an equimolar ratio, and the size exclusion chromatography analysis suggests it forms a heterodecamer, consistent with recent reports. This eIF2B increased protein synthesis in the reconstituted in vitro human translation system. In addition, disease-linked mutations led to subunit dissociation. Furthermore, we crystallized this functional recombinant eIF2B, and the crystals diffracted to 3.0 Å resolution. PMID:27023709

  6. A2B Adenosine Receptor Agonist Improves Erectile Function in Diabetic Rats.

    PubMed

    Wen, Jiaming; Wang, Bohan; Du, Chuanjun; Xu, Gang; Zhang, Zhewei; Li, Yi; Zhang, Nan

    2015-01-01

    Diabetes is an important risk factor for erectile dysfunction (ED). Recent studies have indicated that A2B adenosine receptor (ADORA2B) signaling is essential for penile erection. Thus, we hypothesize that diabetic ED may be attributed to impaired A2B adenosine signaling. To test this hypothesis, we generated diabetic rats by injecting streptozocin as animal model. After 12 weeks, immunohistochemistry staining was used to localize the expression of ADORA2B. Western Blot and quantitative PCR were employed to determine ADORA2B expression level. Intracavernosal pressure (ICP) measurement was used to evaluate erectile function. Diabetic rats received a single intravenous injection of BAY 60-6583, an ADORA2B agonist, or vehicle solution, at 60 min before the ICP measurement. The results showed that ADORA2B expressed in the nerve bundle, smooth muscle, and endothelium in penile tissue of control mice. Western Blot and quantitative PCR results indicated that the expression levels of ADORA2B protein and mRNA were significantly reduced in penile tissues of diabetic rats. Functional studies showed that the erectile response induced by electrical stimulation was remarkably decreased in diabetic rats, compared with age-matched control rats. However, at 60 min after BAY 60-6583 treatment, the erectile function was improved in diabetic rats, suggesting that enhancement of ADORA2B signaling may improve erectile function in diabetic ED. This preclinical study has revealed a previously unrecognized therapeutic possibility of BAY 60-6583 as an effective and mechanism-based drug to treat diabetic ED. In conclusion, we propose that impaired A2B adenosine signaling is one of the pathological mechanisms of diabetic ED. PMID:26447087

  7. Cytochrome P450 2B Diversity and Dietary Novelty in the Herbivorous, Desert Woodrat (Neotoma lepida)

    PubMed Central

    Malenke, Jael R.; Magnanou, Elodie; Thomas, Kirk; Dearing, M. Denise

    2012-01-01

    Detoxification enzymes play a key role in plant-herbivore interactions, contributing to the on-going evolution of ecosystem functional diversity. Mammalian detoxification systems have been well studied by the medical and pharmacological industries to understand human drug metabolism; however, little is known of the mechanisms employed by wild herbivores to metabolize toxic plant secondary compounds. Using a wild rodent herbivore, the desert woodrat (Neotoma lepida), we investigated genomic structural variation, sequence variability, and expression patterns in a multigene subfamily involved in xenobiotic metabolism, cytochrome P450 2B (CYP2B). We hypothesized that differences in CYP2B expression and sequence diversity could explain differential abilities of woodrat populations to consume native plant toxins. Woodrats from two distinct populations were fed diets supplemented with either juniper (Juniperus osteosperma) or creosote bush (Larrea tridentata), plants consumed by woodrats in their respective desert habitats. We used Southern blot and quantitative PCR to determine that the genomic copy number of CYP2B in both populations was equivalent, and similar in number to known rodent copy number. We compared CYP2B expression patterns and sequence diversity using cloned hepatic CYP2B cDNA. The resulting sequences were very diverse, and clustered into four major clades by amino acid similarity. Sequences from the experimental treatments were distributed non-randomly across a CYP2B tree, indicating unique expression patterns from woodrats on different diets and from different habitats. Furthermore, within each major CYP2B clade, sequences shared a unique combination of amino acid residues at 13 sites throughout the protein known to be important for CYP2B enzyme function, implying differences in the function of each major CYP2B variant. This work is the most comprehensive investigation of the genetic diversity of a detoxification enzyme subfamily in a wild mammalian

  8. Transcription factor activating protein 2 beta (TFAP2B) mediates noradrenergic neuronal differentiation in neuroblastoma.

    PubMed

    Ikram, Fakhera; Ackermann, Sandra; Kahlert, Yvonne; Volland, Ruth; Roels, Frederik; Engesser, Anne; Hertwig, Falk; Kocak, Hayriye; Hero, Barbara; Dreidax, Daniel; Henrich, Kai-Oliver; Berthold, Frank; Nürnberg, Peter; Westermann, Frank; Fischer, Matthias

    2016-02-01

    Neuroblastoma is an embryonal pediatric tumor that originates from the developing sympathetic nervous system and shows a broad range of clinical behavior, ranging from fatal progression to differentiation into benign ganglioneuroma. In experimental neuroblastoma systems, retinoic acid (RA) effectively induces neuronal differentiation, and RA treatment has been therefore integrated in current therapies. However, the molecular mechanisms underlying differentiation are still poorly understood. We here investigated the role of transcription factor activating protein 2 beta (TFAP2B), a key factor in sympathetic nervous system development, in neuroblastoma pathogenesis and differentiation. Microarray analyses of primary neuroblastomas (n = 649) demonstrated that low TFAP2B expression was significantly associated with unfavorable prognostic markers as well as adverse patient outcome. We also found that low TFAP2B expression was strongly associated with CpG methylation of the TFAP2B locus in primary neuroblastomas (n = 105) and demethylation with 5-aza-2'-deoxycytidine resulted in induction of TFAP2B expression in vitro, suggesting that TFAP2B is silenced by genomic methylation. Tetracycline inducible re-expression of TFAP2B in IMR-32 and SH-EP neuroblastoma cells significantly impaired proliferation and cell cycle progression. In IMR-32 cells, TFAP2B induced neuronal differentiation, which was accompanied by up-regulation of the catecholamine biosynthesizing enzyme genes DBH and TH, and down-regulation of MYCN and REST, a master repressor of neuronal genes. By contrast, knockdown of TFAP2B by lentiviral transduction of shRNAs abrogated RA-induced neuronal differentiation of SH-SY5Y and SK-N-BE(2)c neuroblastoma cells almost completely. Taken together, our results suggest that TFAP2B is playing a vital role in retaining RA responsiveness and mediating noradrenergic neuronal differentiation in neuroblastoma. PMID:26598443

  9. Transition Metal Complexes of Quinolino[3,2-b]benzodiazepine and Quinolino[3,2-b]benzoxazepine: Synthesis, Characterization, and Antimicrobial Studies

    PubMed Central

    Basavaraju, B.; Bhojya Naik, Halehatty S.; Prabhakara, Mustur C.

    2007-01-01

    The synthesis and characterization of title complexes of the ligand Quinolino[3,2-b]benzodiazepine (QBD) and Quinolino[3,2-b]benzoxazepine (QBO) are reported. The complexes have been characterized by elemental analysis, molar conductance, magnetic studies, IR, H1 NMR, and UV-visible studies. They have the stoichiometry [ML2C12], where M=Co(II)/Ni(II), L=QBD/QBO, and [MLC12], where M=Zn(II)/Cd(II), L=QBD/QBO. The antibacterial and antifungal activity of the metal complexes has been investigated. The complexes were found to have higher antimicrobial activity than the parent ligand. PMID:18273383

  10. Dentalwerkstoffe und Dentalimplantate - Teil 2

    NASA Astrophysics Data System (ADS)

    Faltermeier, Andreas

    Wie in allen Bereichen der Medizin findet auch in der Zahnmedizin eine kontinuierliche Weiterentwicklung der verwendeten Werkstoffe statt. Gerade für Zahnersatz werden Werkstoffe gesucht, die zum einen ästhetisch, zum anderen haltbar und darüber hinaus auch körperverträglich sind. Auch steigt immer mehr der Wunsch der Patienten nach ästhetischen und zugleich biokompatiblen Materialien. Wurde früher fast ausschließlich als Füllungsmaterial im Seitenzahngebiet quecksilberhaltiges Amalgam verwendet, hat der Zahnarzt heutzutage eine große Auswahl an verschiedenen zahnfarbenen Materialien: zum einen werden sog. Komposite verwendet, das aus einer Polymermatrix mit eingebetteten Füllstoffen besteht, zum anderen können diverse Dentalkeramiken verwendet werden. Besonders die Verwendung von Hochleistungskeramiken, wie beispielsweise Zirkonoxid, das sich bereits als Bremsscheiben für Sportwägen, Hitzeschilde im Space Shuttle und als Kugelköpfe künstlicher Hüftgelenke bewährt hat, spielt heutzutage eine große Rolle bei der Verdrängung des Metalls aus der Mundhöhle. War es früher nur möglich, einen verloren gegangen Zahn mittels einer Brücke, die ein Beschleifen der Nachbarzähne zur Folge hat, oder durch herausnehmbaren Zahnersatz zu ersetzen, ist es heutzutage mit der modernen Implantologie möglich, Zahnersatz zahnschonend einzugliedern. Auch kann mittels Dentalimplantaten dem Wunsch vieler Patienten nach festem Zahnersatz anstelle eines herausnehmbaren Zahnersatzes entsprochen werden. So kann mit Hilfe neuer biokompatiblen Werkstoffe sowohl der ästhetische Anspruch befriedigt als auch das Selbstwertgefühl vieler Patienten angehoben werden.

  11. 50 CFR Table 2b to Part 660... - 2014, and Beyond, Allocations by Species or Species Group

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 50 Wildlife and Fisheries 13 2013-10-01 2013-10-01 false 2014, and Beyond, Allocations by Species or Species Group 2b Table 2b to Part 660, Subpart C Wildlife and Fisheries FISHERY CONSERVATION AND... WEST COAST STATES Pt. 660, Subpt. C, Table 2b Table 2b to Part 660, Subpart C—2014, and...

  12. Signatures of spin-glass behaviour in PrIr2B2 and heavy fermion behaviour in PrIr2B2C.

    PubMed

    Anupam; Anand, V K; Hossain, Z; Adroja, D T; Geibel, C

    2011-09-21

    The magnetic and transport properties of PrIr(2)B(2) and PrIr(2)B(2)C have been investigated by dc and ac magnetic susceptibility, specific heat, electrical resistivity and magnetoresistance measurements. PrIr(2)B(2) forms in CaRh(2)B(2)-type orthorhombic crystal structure (space group Fddd). At low fields the dc magnetic susceptibility of PrIr(2)B(2) exhibits a sharp anomaly near 46 K which is followed by an abrupt increase below 10 K with a peak at 6 K, and split-up in ZFC and FC data below 46 K. In contrast, the specific heat exhibits only a broad Schottky type hump near 9 K which indicates that there is no long range magnetic order in this compound. The thermo-remanent magnetization is found to decay very slowly with a mean relaxation time τ = 3917 s. An ac magnetic susceptibility measurement also observes two sharp anomalies; the peak positions strongly depend on the frequency and shift towards high temperature with an increase in frequency, obeying the Vogel-Fulcher law as expected for a canonical spin-glass system. The two spin-glass transitions occur at freezing temperatures T(f1) = 36 K and T(f2) = 3.5 K with shifts in the freezing temperatures per decade of frequency δT(f1) = 0.044 and δT(f2) = 0.09. An analysis of the frequency dependence of the transition temperature with critical slowing down, τ(max)/τ(0) = [(T(f)-T(SG))/T(SG)](-zν), gives τ(0) = 10(-7) s and exponent zν = 8, and the Vogel-Fulcher law gives an activation energy of 84 K for T(f1) and 27.5 K for T(f2). While zν = 8 is typical for spin-glass system, the characteristic relaxation time τ(0) = 10(-7) s is very large and comparable to that of superspin-glass systems. An addition of C in PrIr(2)B(2) leads to PrIr(2)B(2)C which forms in LuNi(2)B(2)C-type tetragonal structure (space group I4/mmm) and remains paramagnetic down to 2 K. The specific heat data show a broad Schottky type anomaly, which could be fairly reproduced with CEF analysis which suggests that the ground state is a

  13. Role of peroxynitrite induced structural changes on H2B histone by physicochemical method.

    PubMed

    Khan, M Asad; Alam, Khursheed; Dixit, Kiran; Rizvi, M Moshahid A

    2016-01-01

    Histones are small highly conserved cationic proteins which bind DNA and remain confined in the nucleus. These histones are quite vulnerable to oxidizing and nitrating agents. Peroxynitrite is a powerful oxidant and nitrating agent present in the biological system. In this study, peroxynitrite-induced nitration and oxidation of H2B was assessed by various physicochemical techniques. The carbonyl content and dityrosine were markedly elevated in peroxynitrite-modified H2B histone as compared to the native histone. Cross-linking of H2B was evident on polyacrylamide gel electrophoresis. 3-Nitrotyrosine was present only in peroxynitrite-modified H2B revealed by HPLC. The results showed that peroxynitrite-mediated nitration and oxidation in H2B histone exhibited hyperchromicity, decrease of tyrosine fluorescence accompanied by increase in ANS-binding specific fluorescence, loss of β-sheet structure, appearance of new peak in FT-IR, increase in melting temperature and also loss of α-helix to produce a partially folded structure in comparison to intrinsically disordered structure of native H2B histone. We concluded that the H2B histone, a constituent of core histones, is highly sensitive to peroxynitrite and can adopt different structures under nitrosative and oxidative stress in order to protect the packaged DNA from the deleterious insult of peroxynitrite. PMID:26536630

  14. Structural characterization and antiviral effect of a novel polysaccharide PSP-2B from Prunellae Spica.

    PubMed

    Ma, Feng-Wei; Kong, Si-Yuan; Tan, Hong-Sheng; Wu, Rong; Xia, Bing; Zhou, Yan; Xu, Hong-Xi

    2016-11-01

    In the present study, a novel polysaccharide, PSP-2B, was isolated from aqueous extracts of Prunellae Spica by direct ultrafiltration membrane separation and gel chromatography purification. PSP-2B is a partially sulphated polysaccharide with a molecular weight of approximately 32kDa. Its sulfate content is 10.59% by elemental analysis. The major sugars comprising PSP-2B are arabinose, galactose and mannose, in addition to small amounts of glucose and uronic acids. The framework of PSP-2B is speculated to be a branched arabinogalactomannan, and the side chains are terminated primarily by the Araf residues. PSP-2B also contains 2.98% protein. PSP-2B exhibits activity against herpes simplex virus (HSV), with a half maximal inhibitory concentration (IC50) of approximately 69μg/mL for HSV-1 and 49μg/mL for HSV-2. However, PSP-2B demonstrated no cytotoxicity even when its concentration was increased to 1600μg/mL, suggesting that it has potential as an anti-HSV drug candidate. PMID:27516321

  15. CDKN2B expression in adipose tissue of familial combined hyperlipidemia patients[S

    PubMed Central

    Horswell, Stuart D.; Fryer, Lee G. D.; Hutchison, Claire E.; Zindrou, Dlear; Speedy, Helen E.; Town, Margaret-M.; Duncan, Emma J.; Sivapackianathan, Rasheeta; Patel, Hetal N.; Jones, Emma L.; Braithwaite, Adam; Salm, Max P. A.; Neuwirth, Claire K. Y.; Potter, Elizabeth; Anderson, Jonathan R.; Taylor, Kenneth M.; Seed, Mary; Betteridge, D. John; Crook, Martin A.; Wierzbicki, Anthony S.; Scott, James; Naoumova, Rossi P.; Shoulders, Carol C.

    2013-01-01

    The purpose of this study was to determine the core biological processes perturbed in the subcutaneous adipose tissue of familial combined hyperlipidemia (FCHL) patients. Annotation of FCHL and control microarray datasets revealed a distinctive FCHL transcriptome, characterized by gene expression changes regulating five overlapping systems: the cytoskeleton, cell adhesion and extracellular matrix; vesicular trafficking; lipid homeostasis; and cell cycle and apoptosis. Expression values for the cell-cycle inhibitor CDKN2B were increased, replicating data from an independent FCHL cohort. In 3T3-L1 cells, CDKN2B knockdown induced C/EBPα expression and lipid accumulation. The minor allele at SNP site rs1063192 (C) was predicted to create a perfect seed for the human miRNA-323b-5p. A miR-323b-5p mimic significantly reduced endogenous CDKN2B protein levels and the activity of a CDKN2B 3′UTR luciferase reporter carrying the rs1063192 C allele. Although the allele displayed suggestive evidence of association with reduced CDKN2B mRNA in the MuTHER adipose tissue dataset, family studies suggest the association between increased CDKN2B expression and FCHL-lipid abnormalities is driven by factors external to this gene locus. In conclusion, from a comparative annotation analysis of two separate FCHL adipose tissue transcriptomes and a subsequent focus on CDKN2B, we propose that dysfunctional adipogenesis forms an integral part of FCHL pathogenesis. PMID:24103848

  16. Anderson lattice in the intermediate valence compound Ce3Ni2B2N3-δ

    NASA Astrophysics Data System (ADS)

    Ali, Tahir; Bauer, Ernst; Hilscher, Gerfried; Michor, Herwig

    2011-03-01

    We have studied magnetic, thermodynamic, and transport properties of Ce3Ni2B2N3-δ and its solid solution with the Tc≃13 K superconductor La3Ni2B2N3-δ. The solid solution (La,Ce)3Ni2B2N3-δ reveals a rapid reduction of Tc by increasing the Ce content with a complete suppression of superconductivity at the composition La2.85Ce0.15Ni2B2N3-δ. The low-temperature properties characterize Ce3Ni2B2N3-δ as an intermediate valence system with a moderately enhanced Sommerfeld value γ≃54 mJ/mol K2 and a susceptibility χ0≃1.6×10-3 emu/mol, increased by about one order of magnitude as compared to the respective value χ0≃0.2×10-3 emu/mol of superconducting La3Ni2B2N3-δ (γ=26 mJ/mol K2) which serves as reference with a nonmagnetic rare earth ion. The electrical resistivity and thermoelectric power of Ce3Ni2B2N3-δ are analyzed in terms of the degenerate Anderson lattice model revealing a characteristic Kondo temperature TKALM~1100 K.

  17. The A2B adenosine receptor modulates pulmonary hypertension associated with interstitial lung disease.

    PubMed

    Karmouty-Quintana, Harry; Zhong, Hongyan; Acero, Luis; Weng, Tingting; Melicoff, Ernestina; West, James D; Hemnes, Anna; Grenz, Almut; Eltzschig, Holger K; Blackwell, Timothy S; Xia, Yang; Johnston, Richard A; Zeng, Dewan; Belardinelli, Luiz; Blackburn, Michael R

    2012-06-01

    Development of pulmonary hypertension is a common and deadly complication of interstitial lung disease. Little is known regarding the cellular and molecular mechanisms that lead to pulmonary hypertension in patients with interstitial lung disease, and effective treatment options are lacking. The purpose of this study was to examine the adenosine 2B receptor (A(2B)R) as a regulator of vascular remodeling and pulmonary hypertension secondary to pulmonary fibrosis. To accomplish this, cellular and molecular changes in vascular remodeling were monitored in mice exposed to bleomycin in conjunction with genetic removal of the A(2B)R or treatment with the A(2B)R antagonist GS-6201. Results demonstrated that GS-6201 treatment or genetic removal of the A(2B)R attenuated vascular remodeling and hypertension in our model. Furthermore, direct A(2B)R activation on vascular cells promoted interleukin-6 and endothelin-1 release. These studies identify a novel mechanism of disease progression to pulmonary hypertension and support the development of A(2B)R antagonists for the treatment of pulmonary hypertension secondary to interstitial lung disease. PMID:22415303

  18. Functional Analysis of Picornavirus 2B Proteins: Effects on Calcium Homeostasis and Intracellular Protein Trafficking▿

    PubMed Central

    de Jong, Arjan S.; de Mattia, Fabrizio; Van Dommelen, Michiel M.; Lanke, Kjerstin; Melchers, Willem J. G.; Willems, Peter H. G. M.; van Kuppeveld, Frank J. M.

    2008-01-01

    The family Picornaviridae consists of a large group of plus-strand RNA viruses that share a similar genome organization. The nomenclature of the picornavirus proteins is based on their position in the viral RNA genome but does not necessarily imply a conserved function of proteins of different genera. The enterovirus 2B protein is a small hydrophobic protein that, upon individual expression, is localized to the endoplasmic reticulum (ER) and the Golgi complex, reduces ER and Golgi complex Ca2+ levels, most likely by forming transmembrane pores, and inhibits protein trafficking through the Golgi complex. At present, little is known about the function of the other picornavirus 2B proteins. Here we show that rhinovirus 2B, which is phylogenetically closely related to enterovirus 2B, shows a similar subcellular localization and function to those of enterovirus 2B. In contrast, 2B proteins of hepatitis A virus, foot-and-mouth disease virus, and encephalomyocarditis virus, all of which are more distantly related to enteroviruses, show a different localization and have little, if any, effects on Ca2+ homeostasis and intracellular protein trafficking. Our data suggest that the 2B proteins of enterovirus and rhinovirus share the same function in virus replication, while the other picornavirus 2B proteins support the viral life cycle in a different manner. Moreover, we show that an enterovirus 2B protein that is retained in the ER is unable to modify Ca2+ homeostasis and inhibit protein trafficking, demonstrating the importance of Golgi complex localization for its functioning. PMID:18216106

  19. Cloning, expression, and purification of a recombinant Tat-HA-NR2B9c peptide.

    PubMed

    Zhou, Hai-Hui; Zhang, Ai-Xia; Zhang, Yu; Zhu, Dong-Ya

    2012-10-01

    To design a peptide disrupting the interaction between N-methyl-d-aspartate receptors-2B (NR2B) and postsynaptic density protein-95 (PSD-95), a gene fragment encoding a chimeric peptide was constructed using polymerase chain reaction and ligated into a novel expression vector for recombinant expression in a T7 RNA polymerase-based expression system. The chimeric peptide contained a fragment of the cell membrane transduction domain of the human immunodeficiency virus type1 (HIV-1) Tat, a influenza virus hemagglutinin (HA) epitope-tag, and the C-terminal 9 amino acids of NR2B (NR2B9c). We named the chimeric peptide Tat-HA-NR2B9c. The expression plasmid contained a gene fragment encoding the Tat-HA-NR2B9c was ligated to the C-terminal fragment of l-asparaginase (AnsB-C) via a unique acid labile Asp-Pro linker. The recombinant fusion protein was expressed in inclusion body in Escherichia coli under isopropyl β-d-1-thiogalactopyranoside (IPTG) and purified by washing with 2M urea, solubilizing in 4M urea, and then ethanol precipitation. The target chimeric peptide Tat-HA-NR2B9c was released from the fusion partner following acid hydrolysis and purified by isoelectric point precipitation and ultrafiltration. SDS-PAGE analysis and MALDI-TOF-MS analysis showed that the purified Tat-HA-NR2B9c was highly homogeneous. Furthermore, we investigated the effects of Tat-HA-NR2B9c on ischemia-induced cerebral injury in the rats subjected to middle cerebral artery occlusion (MCAO) and reperfusion, and found that the peptide reduced infarct size and improved neurological functions. PMID:22944204

  20. Histone demethylase KDM2B inhibits the chondrogenic differentiation potentials of stem cells from apical papilla.

    PubMed

    Wang, Jing-Jing; Dong, Rui; Wang, Li-Ping; Wang, Jin-Song; Du, Juan; Wang, Song-Lin; Shan, Zhao-Chen; Fan, Zhi-Peng

    2015-01-01

    Mesenchymal stem cells (MSCs) are a reliable resource for tissue regeneration, but the molecular mechanism underlying directed differentiation remains unclear; this has restricted potential MSC applications. Histone methylation, controlled by histone methyltransferases and demethylases, may play a key role in MSCs differentiation. Previous studies determined that KDM2B can regulate the cell proliferation and osteo/dentinogenic differentiation of MSCs. It is not known whether KDM2B is involved in the other cell lineages differentiation of MSCs. Here we used the stem cells from apical papilla (SCAPs) to study the role of KDM2B on the chondrogenic differentiation potentials in MSCs. In this study, Gain- and loss-of-function assays were applied to investigate the role of KDM2B on the chondrogenic differentiation. Alcian Blue Staining and Quantitative Analysis were used to investigate the synthesis of proteoglycans by chondrocytes. Real-time RT-PCR was used to detect the expressions of chondrogenesis related genes. The Alcian Blue staining and Quantitative Analysis results revealed that overexpression of KDM2B decreased the proteoglycans production, and real-time RT-PCR results showed that the expressions of the chondrogenic differentiation markers, COL1, COL2 and SOX9 were inhibited by overexpression of KDM2B in SCAPs. On the contrary, depletion of KDM2B increased the proteoglycans production, and inhibited the expressions of COL1, COL2 and SOX9. In conclusion, our results indicated that KDM2B is a negative regulator of chondrogenic differentiation in SCAPs and suggest that inhibition of KDM2B might improve MSC mediated cartilage regeneration. PMID:25932147

  1. Trans-complementation of a genetic defect in the coxsackie B3 virus 2B protein.

    PubMed

    van Kuppeveld, Frank J M; van den Hurk, Patrick J J C; Schrama, Ina W J; Galama, Jochem M D; Melchers, Willem J G

    2002-02-01

    The enterovirus 2B protein contains a putative amphipathic alpha-helix that includes three positively charged and one negatively charged residue. Previously, we observed that replacement of the glutamic acid-40 residue with a lysine residue (mutation 2B-E[40]K) in the amphipathic alpha-helix of the coxsackie B3 virus 2B protein resulted in a quasi-infectious phenotype. On one occasion, however, transfection of 2B-E[40]K RNA transcripts gave rise to a virus stock in which the mutation was retained. This study was aimed at elucidating the molecular mechanism underlying this observation. Sequence analysis of the viral RNA provided no evidence for a second-site suppression mutation that rescued the defect of the 2B-E[40]K mutation in cis. Therefore, the possibility was considered that the defect caused by the 2B-E[40]K mutation was complemented in trans by viable revertants that had emerged in the virus population. The transfection-derived virus stock indeed contained a small fraction of (pseudo)revertant viruses, carrying the original glutamic acid-40, threonine-40 or asparagine-40, rather than the introduced lysine-40. Consistent with the idea that the 2B-E[40]K virus is unable to grow without the aid of trans-acting wild-type(-like) proteins, only the (pseudo)revertant viruses were able to produce individual plaques. Further support for the idea of trans-rescue was obtained using a genetic complementation assay, which revealed the occurrence of a low level of trans-complementation of the 2B-E[40]K mutation by wild-type virus. This is the first report that provides evidence that a genetic defect in the enterovirus 2B protein can be complemented in trans. PMID:11807227

  2. NITRIC OXIDE-DEPENDENT PROTEASOMAL DEGRADATION OF CYTOCHROME P450 2B PROTEINS*

    PubMed Central

    Lee, Choon-Myung; Kim, Bong-Yoon; Li, Lian; Morgan, Edward T.

    2007-01-01

    Exposure to inflammatory agents or cytokines causes the suppression of cytochrome P450 (CYP) enzyme activities and expression in liver and primary hepatocyte cultures. We showed previously that phenobarbital-induced CYP2B protein is down-regulated in primary cultures of rat hepatocytes following exposure to bacterial endotoxin (LPS) in a nitric oxide (NO)-dependent manner. In the present study, we found that CYP2B proteins in primary rat hepatocyte cultures were suppressed more than 60% after 6h treatment with interleukin-1β (IL-1). This effect was NO-dependent, and treatment of cells with the NO-donors (Z)-1-[2-(2-aminoethyl)-N-(2-ammonioethyl)amino] diazen-1-ium-1,2-diolate (NOC-18), S-nitrosoglutathione (GSNO), and S-nitroso, N-acetylpenicillamine (SNAP) also suppressed CYP2B proteins. However, the down-regulation by IL-1 was insensitive to inhibition of cGMP-dependent protein kinases. The down-regulation by IL-1 or NO donors was abolished by treatments with the proteasome inhibitors MG132 and lactacystin that did not affect NO production. The calpain inhibitor E64-d or the lysosomal protease inhibitors NH4Cl and chloroquine did not attenuate the down-regulation of CYP2B by IL-1. Treatment of HeLa cells expressing c-myc-tagged CYP2B1 with NOC-18 down-regulated its expression and enhanced its ubiquitination. Treatment of rat liver microsomes with GSNO caused S-nitrosylation of CYP2B protein, and enhanced the ubiquitination pattern of CYP2B compared to unmodified CYP2B in an in vitro ubiquitination assay. These data are consistent with the hypothesis that NO-dependent CYP2B ubiquitination and proteasomal degradation are dependent on protein modification by reactive nitrogen species. PMID:17993647

  3. The SH2B1 Adaptor Protein Associates with a Proximal Region of the Erythropoietin Receptor*

    PubMed Central

    Javadi, Mojib; Hofstätter, Edda; Stickle, Natalie; Beattie, Bryan K.; Jaster, Robert; Carter-Su, Christin; Barber, Dwayne L.

    2012-01-01

    Gene targeting experiments have shown that the cytokine erythropoietin (EPO), its cognate erythropoietin receptor (EPO-R), and associated Janus tyrosine kinase, JAK2, are all essential for erythropoiesis. Structural-functional and murine knock-in experiments have suggested that EPO-R Tyr-343 is important in EPO-mediated mitogenesis. Although Stat5 binds to EPO-R phosphotyrosine 343, the initial Stat5-deficient mice did not have profound erythroid abnormalities suggesting that additional Src homology 2 (SH2) domain-containing effectors may bind to EPO-R Tyr-343 and couple to downstream signaling pathways. We have utilized cloning of ligand target (COLT) screening to demonstrate that EPO-R Tyr(P)-343 and Tyr(P)-401 bind to the SH2 domain-containing adaptor protein SH2B1β. Immunoprecipitation and in vitro mixing experiments reveal that EPO-R binds to SH2B1 in an SH2 domain-dependent manner and that the sequence that confers SH2B1 binding to the EPO-R is pYXXL. Previous studies have shown that SH2B1 binds directly to JAK2, but we show that in hematopoietic cells, SH2B1β preferentially associates with the EPO-R. SH2B1 is capable of constitutive association with EPO-R, which is necessary for its optimal SH2-dependent recruitment to EPO-R-Tyr(P)-343/Tyr(P)-401. We also demonstrate that SH2B1 is responsive to EPO stimulation and becomes phosphorylated, most likely on serines/threonines, in an EPO dose- and time-dependent manner. In the absence of SH2B1, we observe enhanced activation of signaling pathways downstream of the EPO-R, indicating that SH2B1 is a negative regulator of EPO signaling. PMID:22669948

  4. The SH2B1 adaptor protein associates with a proximal region of the erythropoietin receptor.

    PubMed

    Javadi, Mojib; Hofstätter, Edda; Stickle, Natalie; Beattie, Bryan K; Jaster, Robert; Carter-Su, Christin; Barber, Dwayne L

    2012-07-27

    Gene targeting experiments have shown that the cytokine erythropoietin (EPO), its cognate erythropoietin receptor (EPO-R), and associated Janus tyrosine kinase, JAK2, are all essential for erythropoiesis. Structural-functional and murine knock-in experiments have suggested that EPO-R Tyr-343 is important in EPO-mediated mitogenesis. Although Stat5 binds to EPO-R phosphotyrosine 343, the initial Stat5-deficient mice did not have profound erythroid abnormalities suggesting that additional Src homology 2 (SH2) domain-containing effectors may bind to EPO-R Tyr-343 and couple to downstream signaling pathways. We have utilized cloning of ligand target (COLT) screening to demonstrate that EPO-R Tyr(P)-343 and Tyr(P)-401 bind to the SH2 domain-containing adaptor protein SH2B1β. Immunoprecipitation and in vitro mixing experiments reveal that EPO-R binds to SH2B1 in an SH2 domain-dependent manner and that the sequence that confers SH2B1 binding to the EPO-R is pYXXL. Previous studies have shown that SH2B1 binds directly to JAK2, but we show that in hematopoietic cells, SH2B1β preferentially associates with the EPO-R. SH2B1 is capable of constitutive association with EPO-R, which is necessary for its optimal SH2-dependent recruitment to EPO-R-Tyr(P)-343/Tyr(P)-401. We also demonstrate that SH2B1 is responsive to EPO stimulation and becomes phosphorylated, most likely on serines/threonines, in an EPO dose- and time-dependent manner. In the absence of SH2B1, we observe enhanced activation of signaling pathways downstream of the EPO-R, indicating that SH2B1 is a negative regulator of EPO signaling. PMID:22669948

  5. Vaccination of dogs with canine parvovirus type 2b (CPV-2b) induces neutralising antibody responses to CPV-2a and CPV-2c.

    PubMed

    Wilson, Stephen; Illambas, Joanna; Siedek, Elisabeth; Stirling, Catrina; Thomas, Anne; Plevová, Edita; Sture, Gordon; Salt, Jeremy

    2014-09-22

    Since the identification of canine parvovirus type 2, three variants have subsequently been observed differing from the historical CPV-2 and each other by 1-2 amino acids only. As a result there has been considerable research into differential diagnostics, with some researchers indicating there is a need for new vaccines containing different strains of CPV-2. In this study we investigated whether vaccination with a CPV-2b containing vaccine would induce cross-reactive antibody responses to the other CPV-2 variants. Two studies where dogs were vaccinated with a multivalent vaccine, subsequently challenged with CPV-2b and sera samples analysed are presented. Six week old pups with defined serological status were vaccinated twice, three weeks apart and challenged either 5 weeks (MDA override study) or one year after vaccination (duration of immunity study). Sera samples were collected before each vaccination and at periods throughout each study. In each study the antibody profiles were very similar; serological responses against CPV-2a, CPV-2b and CPV-2c were higher than those for CPV-2. Nevertheless, responses against CPV-2 were well above levels considered clinically protective. In each study dogs also showed a rapid increase in antibody titres following vaccination, reached a plateau following second vaccination with a slight decline to challenge after which rapid anamnestic responses were seen. Evaluation of the serological responses suggests vaccination with CPV-2b would cross-protect against CPV-2a and CPV-2c, as well as against CPV-2 which is now extinct in the field. In conclusion we have demonstrated that vaccination of minimum aged dogs with a multivalent vaccine containing the CPV-2b variant strain will induce serological responses which are cross-reactive against all currently circulating field strains, CPV-2a and CPV-2c, and the now extinct field strain CPV-2. PMID:25148778

  6. Hochschule fur Film und Fernsehen (Babelsberg).

    ERIC Educational Resources Information Center

    Neumann, Roland

    1992-01-01

    Describes the Hochschule fur Film und Fernsehen, an institution of higher education for the study of film and television production in Babelsberg, Germany (formerly the German Democratic Republic). Discusses the major reorientations in the school caused by Germany's reunification. (SR)

  7. Satellitenbewegung, band III: Natiirliche und gesteuerte bewegung.

    NASA Astrophysics Data System (ADS)

    Jochim, E. F.

    2014-12-01

    Im dritten Band der Satellitenbewegung werden in fortlaufender Nummerierung einige für Untersuchungen der Bewegung der künstlichen Satelliten wichtige Grundlagen der Astrodynamik mit ausführlichen mathematischen Formelsystemen behandelt. Dazu zählen die unterschiedlichen Aspekte der Bewegung der natürlichen Himmelskörper, die Steuerung und Kontrolle von künstlichen Objekten, und insbesondere die für eine Satellitenbahnanalyse wichtigen physikalischen Beeinflussungen einer Satellitenbewegung. Mathematisch entscheidend ist die Wahl geeigneter Bahnparameter, die ein bestimmtes Bewegungsproblem widerspruchsfrei und singularitätenfrei zu behandeln gestatten. Für die Behandlung routinemäßiger Aufgabenstellungen der Satellitenbewegung, in erster Linie einer präzisen Bahnbestimmung und Bahnverbesserung, kann auf eine Fülle von lehrbuchartigen Monographien verwiesen werden, so dass diese Problematik in der vorliegenden Arbeit nur angedeutet werden soll.

  8. Simulation und virtuelle Realität

    NASA Astrophysics Data System (ADS)

    von Estorff, Otto; Markiewicz, Marian; Özkan, Ali; Zaleski, Olgierd; Blumrich, Reinhard; Genuit, Klaus; Fiebig, André

    Mit Hilfe akustischer Berechnungen ist es möglich, aufwendige Messungen an Fahrzeugprototypen deutlich zu reduzieren. Dieses Kapitel gibt einen kurzen Überblick über die wichtigsten derzeit verfügbaren Methoden. Dabei wird zunächst auf Elementverfahren, wie die Finite-Elemente-Methode (FEM) und die Boundary-Elemente-Methode (BEM), näher eingegangen. Während diese vor allem im tieffrequenten Bereich eingesetzt werden, kommen bei höheren Frequenzen vermehrt Verfahren zum Einsatz, die auf Energieformulierungen beruhen. Exemplarisch wird hier die Funktionsweise und der Einsatz der Statistischen-Energie-Analyse (SEA) erläutert. Anhand von repräsentativen Beispielen werden die Einsatzmöglichkeiten und Grenzen der verschiedenen Verfahren aufgezeigt, wobei vor allem auch auf Vergleiche zwischen Rechnung und Messung eingegangen wird.

  9. Beyond Cohort Selection: An Analytics-Enabled i2b2.

    PubMed

    Gabetta, Matteo; Malovini, Alberto; Bucalo, Mauro; Zini, Elisa; Tibollo, Valentina; Priori, Silvia G; Vettoretti, Simone; Larizza, Cristiana; Bellazzi, Riccardo; Barbarini, Nicola

    2016-01-01

    The i2b2 software is a widely adopted solution for secondary use of clinical data for clinical research, specifically designed for cohort identification. i2b2 is still lacking functionalities for data analysis. The aim of this work is to empower the i2b2 framework enabling clinical researchers to perform statistical analyses for accelerating the process of hypothesis testing. To this aim we have developed a flexible extension of i2b2 able to exploit different statistical engines. We have implemented some first applications for basic statistics and survival analyses, exploiting this extension and accessible through suitable user interfaces designed with a special consideration for usability. PMID:27577448

  10. Kynurenic acid amides as novel NR2B selective NMDA receptor antagonists.

    PubMed

    Borza, István; Kolok, Sándor; Galgóczy, Kornél; Gere, Anikó; Horváth, Csilla; Farkas, Sándor; Greiner, István; Domány, György

    2007-01-15

    A novel series of kynurenic acid amides, ring-enlarged derivatives of indole-2-carboxamides, was prepared and identified as in vivo active NR2B subtype selective NMDA receptor antagonists. The synthesis and SAR studies are discussed. PMID:17074483

  11. H-2b bound to egg lecithin liposomes: biochemical and functional properties.

    PubMed Central

    Rogers, M J

    1982-01-01

    Purified H-2b and H-2a molecules were bound to egg lecithin liposomes by a detergent dialysis procedure. Analysis of the liposomes indicated that only 30-50% of bound H-2b is oriented with the hydrophilic, antigenic portion of the molecule toward the outside of the liposome. Saturation of the liposomes occurred at a ratio of 64 molecules of egg lecithin per molecule of H-2b. Liposomes containing H-2 molecules were capable of stimulating spleen cells from primed donors to produce specific, alloreactive, cytotoxic T lymphocytes in vitro. Stimulation was dependent on adherent cells present in the responder spleen cells. Optimal stimulation occurred with highly saturated liposomes and at a ratio of 4-8 micrograms of H-2b per 8 X 10(6) responder cells. Images Fig. 4 PMID:7116686

  12. Project Description Advanced Fuel Cycle Initiative AFC-2A and AFC-2B Experiments

    SciTech Connect

    AFCI AFC-2A and AFC-2B Experiments Project Executi

    2007-03-01

    The proposed AFC-2A and AFC-2B irradiation experiments are a continuation of the AFC-1 fuel test series currently in progress in the ATR. This document discusses the experiments and the planned activities that will take place.

  13. C-Axis Properties of DyNi2B2C System

    NASA Astrophysics Data System (ADS)

    Lee, W. C.

    2012-02-01

    We have measured the electrical resistivity along c-axis ρc(T, H) of the DyNi2B2C single crystal with the magnetic fields perpendicular to the c-axis and the magnetization isotherms M(H) of the DyNi2B2C single crystal with magnetic fields perpendicular and parallel to the c-axis. We confirmed that Neel temperature TN is 10.3K from the ρc(T) result which is consistent with that from previous ρab(T) result. In addition, the constructed critical fields Hc2(T) curve and magnetic transitions diagram of DyNi2B2C from ρc(T) magnetic fields perpendicular to c-axis is similar to that of ρab(T) result, which is thought to arise that 3 D magnetic structure of DyNi2B2C.

  14. UV damage-induced RNA polymerase II stalling stimulates H2B deubiquitylation.

    PubMed

    Mao, Peng; Meas, Rithy; Dorgan, Kathleen M; Smerdon, Michael J

    2014-09-01

    Histone H2B monoubiquitylation plays an important role in RNA polymerase II (RNAPII) elongation. Whether this modification responds to RNAPII stalling is not yet known. We report that both yeast and human cells undergo a rapid and significant H2B deubiquitylation after exposure to UV irradiation. This deubiquitylation occurs concurrently with UV-induced transcription arrest and is significantly reduced in a DNA damage-bypassing RNAPII yeast mutant. Consistent with these results, yeast deubiquitylases Ubp8 and Ubp10 are associated with the RNAPII complex. Moreover, simultaneous deletion of Ubp8 and Ubp10 leads to a lack of H2B deubiquitylation after UV exposure. Consequently, nucleotide excision repair at an actively transcribed gene locus is decreased, whereas UV-induced RNAPII degradation is increased in ubp8Δubp10Δ mutant cells. These results indicate that eukaryotic cells respond to RNAPII arrest by deubiquitylating H2B to coordinate DNA repair and RNAPII degradation. PMID:25136098

  15. UV damage-induced RNA polymerase II stalling stimulates H2B deubiquitylation

    PubMed Central

    Mao, Peng; Meas, Rithy; Dorgan, Kathleen M.; Smerdon, Michael J.

    2014-01-01

    Histone H2B monoubiquitylation plays an important role in RNA polymerase II (RNAPII) elongation. Whether this modification responds to RNAPII stalling is not yet known. We report that both yeast and human cells undergo a rapid and significant H2B deubiquitylation after exposure to UV irradiation. This deubiquitylation occurs concurrently with UV-induced transcription arrest and is significantly reduced in a DNA damage-bypassing RNAPII yeast mutant. Consistent with these results, yeast deubiquitylases Ubp8 and Ubp10 are associated with the RNAPII complex. Moreover, simultaneous deletion of Ubp8 and Ubp10 leads to a lack of H2B deubiquitylation after UV exposure. Consequently, nucleotide excision repair at an actively transcribed gene locus is decreased, whereas UV-induced RNAPII degradation is increased in ubp8Δubp10Δ mutant cells. These results indicate that eukaryotic cells respond to RNAPII arrest by deubiquitylating H2B to coordinate DNA repair and RNAPII degradation. PMID:25136098

  16. Ground-water flow beneath levee 35A from conservation area 2B, Broward County, Florida

    USGS Publications Warehouse

    Swayze, L.J.

    1988-01-01

    Conservation Area 2B is an area of recharge for the surficial aquifer system in Broward County. Water stored in the conservation area provides the hydraulic potential for downward flow to the high permeability zone of the Biscayne aquifer. A 5.64 ft head differential (average for the period of record) between water levels in Conservation Area 2B and water levels in the adjacent levee 35A borrow canal causes water to leak into the canal at an average rate of about 0.0022 cu ft per sec per lineal foot of canal and accounts for a loss of 0.013 foot per day of surface water from Conservation Area 2B. Amounts of canal leakage and underflow are constantly changing and are dependent upon the head differential between Conservation Area 2B and the levee 35A borrow canal. (Author 's abstract)

  17. Hydroxysteroid sulfotransferase 2B1b expression and localization in normal human brain

    PubMed Central

    Salman, Emily D.; Faye-Petersen, Ona; Falany, Charles N.

    2012-01-01

    Steroid sulfonation in the human brain has not been well characterized. The major sulfotransferase (SULT) isoforms that conjugate steroids in humans are SULT1E1, SULT2A1, and SULT2B1b. SULT2B1b catalyzes the sulfonation of 3β-hydroxysteroids, including neurosteroids dehydroepiandrosterone and pregnenolone, as well as cholesterol and several hydroxycholesterols. SULT2B1b mRNA and protein expression were detected in adult and fetal human brain sections, whereas neither mRNA, nor protein expression were identified for SULT1E1 or SULT2A1. Using immunohistochemical analysis, SULT2B1b expression was detected in neurons and oligodendrocytes in adult brain and in epithelial tissues in 28-week-old fetal brain. Sulfonation of cholesterol, oxysterols, and neurosteroids in the brain is apparently catalyzed by SULT2B1b since expression of neither SULT2A1 nor SULT1E1 was detected in human brain sections. SULT2B1b mRNA and protein were also detected in human U373-MG glioblastoma cells. Both mRNA and protein expression of liver X receptor (LXR)-β, but not LXR-α, were detected in U373-MG cells, and LXR-β activation resulted in a decrease in SULT2B1b protein expression. Since hydroxycholesterols are important physiological LXR activators, this suggests a role for regulation of sterol metabolism by LXR and SULT2B1b. Therefore, elucidating key enzymes in the metabolism of cholesterol and neurosteroids could help define the properties of steroid conjugation in the human brain. PMID:24683427

  18. Multiple endocrine neoplasias type 2B and RET proto-oncogene

    PubMed Central

    2012-01-01

    Multiple Endocrine Neoplasia type 2B (MEN 2B) is an autosomal dominant complex oncologic neurocristopathy including medullary thyroid carcinoma, pheochromocytoma, gastrointestinal disorders, marphanoid face, and mucosal multiple ganglioneuromas. Medullary thyroid carcinoma is the major cause of mortality in MEN 2B syndrome, and it often appears during the first years of life. RET proto-oncogene germline activating mutations are causative for MEN 2B. The 95% of MEN 2B patients are associated with a point mutation in exon 16 (M918/T). A second point mutation at codon 883 has been found in 2%-3% of MEN 2B cases. RET proto-oncogene is also involved in different neoplastic and not neoplastic neurocristopathies. Other RET mutations cause MEN 2A syndrome, familial medullary thyroid carcinoma, or Hirschsprung's disease. RET gene expression is also involved in Neuroblastoma. The main diagnosis standards are the acetylcholinesterase study of rectal mucosa and the molecular analysis of RET. In our protocol the rectal biopsy is, therefore, the first approach. RET mutation detection offers the possibility to diagnose MEN 2B predisposition at a pre-clinical stage in familial cases, and to perform an early total prophylactic thyroidectomy. The surgical treatment of MEN 2B is total thyroidectomy with cervical limphadenectomy of the central compartment of the neck. When possible, this intervention should be performed with prophylactic aim before 1 year of age in patients with molecular genetic diagnosis. Recent advances into the mechanisms of RET proto-oncogene signaling and pathways of RET signal transduction in the development of MEN 2 and MTC will allow new treatment possibilities. PMID:22429913

  19. Expressing Status and Correlation of ARID1A and Histone H2B on Breast Cancer

    PubMed Central

    Wu, Yan; Gu, Yan; Guo, Shanyu; Dai, Qiancheng; Zhang, Wei

    2016-01-01

    ARID1A is one of the important cancer-related genes and regulates transcription of certain genes by altering chromatin structure. Inactivated mutations and decreased expression of ARID1A gene have been reported in several kinds of cancer. Histone H2B is a major component of chromatin and encoded by HIST1H2BE. The goal of the study is to evaluate expressing status of ARID1A and H2B as well as their correlation on breast cancer. Gene expression profiles of ARID1A and H2B on Oncomine database are analyzed. Tissue microarray of breast cancer was used for examination of ARID1A and H2B expression by immunohistochemistry. As a result, the disagreement of ARID1A expression was found, while HIST1H2BE expression is elevated in 4 out of 5 datasets on Oncomine database. There were 15 cases (20%) of breast cancers that were positive for ARID1A. Fifty-eight out of 75 cases of breast cancer (77.3%) were highly expressed for H2B protein and 17 cases (22.7%) were low expressed for H2B protein. All cases with ARID1A expression are overlapped with H2B high expression. Among 15 cases with ARID1A and H2B coexpression, 13 are invasive ductal carcinoma and 2 are mucinous carcinoma. Our results indicate that ARID1A gene may be involved in carcinogenesis of some subtypes of breast cancer. PMID:26904685

  20. Strong Specific Inhibition of UDP-glucuronosyltransferase 2B7 by Atractylenolide I and III.

    PubMed

    Zhang, Qian; Cao, Yun-Feng; Ran, Rui-Xue; Li, Rong-Shan; Wu, Xue; Dong, Pei-Pei; Zhang, Yan-Yan; Hu, Cui-Min; Wang, Wei-Ming

    2016-01-01

    Drug-metabolizing enzymes inhibition-based drug-drug interaction remains to be the key limiting factor for the research and development of efficient herbal components to become clinical drugs. The present study aims to determine the inhibition of uridine 5'-diphospho-glucuronosyltransferases (UGTs) isoforms by two important efficient herbal ingredients isolated from Atractylodes macrocephala Koidz, atractylenolide I and III. In vitro recombinant UGTs-catalysed glucuronidation of 4-methylumbelliferone was used to determine the inhibition capability and kinetics of atractylenolide I and III towards UGT2B7, and in silico docking method was employed to explain the possible mechanism. Atractylenolide I and III exhibited specific inhibition towards UGT2B7, with negligible influence towards other UGT isoforms. Atractylenolide I exerted stronger inhibition potential than atractylenolide III towards UGT2B7, which is attributed to the different hydrogen bonds and hydrophobic interactions. Inhibition kinetic analysis was performed for the inhibition of atractylenolide I towards UGT2B7. Inhibition kinetic determination showed that atractylenolide I competitively inhibited UGT2B7, and inhibition kinetic parameter (Ki) was calculated to be 6.4 μM. In combination of the maximum plasma concentration of atractylenolide I after oral administration of 50 mg/kg atractylenolide I, the area under the plasma concentration-time curve ration AUCi /AUC was calculated to be 1.17, indicating the highly possible drug-drug interaction between atractylenolide I and drugs mainly undergoing UGT2B7-catalysed metabolism. PMID:26536846

  1. HIPK2 controls cytokinesis and prevents tetraploidization by phosphorylating histone H2B at the midbody.

    PubMed

    Rinaldo, Cinzia; Moncada, Alice; Gradi, Alessandra; Ciuffini, Laura; D'Eliseo, Donatella; Siepi, Francesca; Prodosmo, Andrea; Giorgi, Alessandra; Pierantoni, Giovanna M; Trapasso, Francesco; Guarguaglini, Giulia; Bartolazzi, Armando; Cundari, Enrico; Schininà, M Eugenia; Fusco, Alfredo; Soddu, Silvia

    2012-07-13

    Failure in cytokinesis, the final step in cell division, by generating tetra- and polyploidization promotes chromosomal instability, a hallmark of cancer. Here we show that HIPK2, a kinase involved in cell fate decisions in development and response to stress, controls cytokinesis and prevents tetraploidization through its effects on histone H2B. HIPK2 binds and phosphorylates histone H2B at S14 (H2B-S14(P)), and the two proteins colocalize at the midbody. HIPK2 depletion by targeted gene disruption or RNA interference results in loss of H2B-S14(P) at the midbody, prevention of cell cleavage, and tetra- and polyploidization. In HIPK2 null cells, restoration of wild-type HIPK2 activity or expression of a phosphomimetic H2B-S14D derivative abolishes cytokinesis defects and rescues cell proliferation, showing that H2B-S14(P) is required for a faithful cytokinesis. Overall, our data uncover mechanisms of a critical HIPK2 function in cytokinesis and in the prevention of tetraploidization. PMID:22658722

  2. Ni(II) affects ubiquitination of core histones H2B and H2A

    SciTech Connect

    Karaczyn, Aldona A.; Golebiowski, Filip; Kasprzak, Kazimierz S. . E-mail: kasprkaz@mail.ncifcrf.gov

    2006-10-15

    The molecular mechanisms of nickel-induced malignant cell transformation include effects altering the structure and covalent modifications of core histones. Previously, we found that exposure of cells to Ni(II) resulted in truncation of histones H2A and H2B and thus elimination of some modification sites. Here, we investigated the effect of Ni(II) on one such modification, ubiquitination, of histones H2B and H2A in nuclei of cultured 1HAEo- and HPL1D human lung cells. After 1-5 days of exposure, Ni(II) up to 0.25 mM stimulated mono-ubiquitination of both histones, while at higher concentrations a suppression was found. Di-ubiquitination of H2A was not affected except for a drop after 5 days at 0.5 mM Ni(II). The decrease in mono-ubiquitination coincided with the appearance of truncated H2B that lacks the K120 ubiquitination site. However, prevention of truncation did not avert the decrease of H2B ubiquitination, indicating mechanistic independence of these effects. The changes in H2B ubiquitination did not fully coincide with concurrent changes in the nuclear levels of the ubiquitin-conjugating enzymes Rad6 and UbcH6. Overall, our results suggest that dysregulation of H2B ubiquitination is a part of Ni(II) adverse effects on gene expression and DNA repair which may assist in cell transformation.

  3. eIF2B: recent structural and functional insights into a key regulator of translation.

    PubMed

    Wortham, Noel C; Proud, Christopher G

    2015-12-01

    The eukaryotic translation initiation factor (eIF) eIF2B is a key regulator of mRNA translation, being the guanine nt exchange factor (GEF) responsible for the recycling of the heterotrimeric G-protein, eIF2, which is required to allow translation initiation to occur. Unusually for a GEF, eIF2B is a multi-subunit protein, comprising five different subunits termed α through ε in order of increasing size. eIF2B is subject to tight regulation in the cell and may also serve additional functions. Here we review recent insights into the subunit organization of the mammalian eIF2B complex, gained both from structural studies of the complex and from studies of mutations of eIF2B that result in the neurological disorder leukoencephalopathy with vanishing white matter (VWM). We will also discuss recent data from yeast demonstrating a novel function of the eIF2B complex key for translational regulation. PMID:26614666

  4. Yields of O2(b 1 Sigma g +) from reactions of HO2. [in planetary atmospheres

    NASA Technical Reports Server (NTRS)

    Keyser, L. F.; Choo, K. Y.; Leu, M. T.

    1985-01-01

    The production of O2(b 1 Sigma g +) has been monitored for several reactions of the HO2 radical at 300 K using a discharge-flow apparatus with resonance fluorescence and chemiluminescence detection. In all cases, the resulting quantum efficiencies were found to be less than 0.03. O2(b) was observed when F atoms were added to H2O2 in the gas phase. The signal strengths of O2(b) were proportional to initial concentrations of HO2 formed by the F + H2O2 reaction. Observed /O2(b)/, /HO2/, and /OH/ vs /F/0 were analyzed using a simple three-step mechanism and a more complete computer simulation with 22 reaction steps. The results indicate that the F + HO2 reaction yields O2(b) with an efficiency of (3.6 + or - 1.4) x 10 to the -3rd. Yields from the O + OH2 reaction were less than 0.02, indicating that this reaction cannot be a major source of the O2(b) emission observed in the earth's nightglow.

  5. DAPK1 Interaction with NMDA Receptor NR2B Subunits Mediates Brain Damage in Stroke

    PubMed Central

    Tu, Weihong; Xu, Xin; Peng, Lisheng; Zhong, Xiaofen; Zhang, Wenfeng; Soundarapandian, Mangala M.; Balel, Cherine; Wang, Manqi; Jia, Nali; Zhang, Wen; Lew, Frank; Chan, Sic Lung; Chen, Yanfang; Lu, Youming

    2010-01-01

    SUMMARY N-methyl-D-aspartate (NMDA) receptors constitute a major subtype of glutamate receptors at extra-synaptic sites that link multiple intracellular catabolic processes responsible for irreversible neuronal death. Here, we report that cerebral ischemia recruits death-associated protein kinase 1 (DAPK1) into the NMDA receptor NR2B protein complex in the cortex of adult mice. DAPK1 directly binds with the NMDA receptor NR2B C-terminal tail consisting of amino acid 1292–1304 (NR2BCT). A constitutively active DAPK1 phosphorylates NR2B subunit at Ser-1303 and in turn enhances the NR1/NR2B receptor channel conductance. Genetic deletion of DAPK1 or administration of NR2BCT that uncouples an activated DAPK1 from an NMDA receptor NR2B subunit in vivo in mice blocks injurious Ca2+ influx through NMDA receptor channels at extrasynaptic sites and protects neurons against cerebral ischemic insults. Thus, DAPK1 physically and functionally interacts with the NMDA receptor NR2B subunit at extra-synaptic sites and this interaction acts as a central mediator for stroke damage. PMID:20141836

  6. Allosteric inhibition of the NS2B-NS3 protease from dengue virus.

    PubMed

    Yildiz, Muslum; Ghosh, Sumana; Bell, Jeffrey A; Sherman, Woody; Hardy, Jeanne A

    2013-12-20

    Dengue virus is the flavivirus that causes dengue fever, dengue hemorrhagic disease, and dengue shock syndrome, which are currently increasing in incidence worldwide. Dengue virus protease (NS2B-NS3pro) is essential for dengue virus infection and is thus a target of therapeutic interest. To date, attention has focused on developing active-site inhibitors of NS2B-NS3pro. The flat and charged nature of the NS2B-NS3pro active site may contribute to difficulties in developing inhibitors and suggests that a strategy of identifying allosteric sites may be useful. We report an approach that allowed us to scan the NS2B-NS3pro surface by cysteine mutagenesis and use cysteine reactive probes to identify regions of the protein that are susceptible to allosteric inhibition. This method identified a new allosteric site utilizing a circumscribed panel of just eight cysteine variants and only five cysteine reactive probes. The allosterically sensitive site is centered at Ala125, between the 120s loop and the 150s loop. The crystal structures of WT and modified NS2B-NS3pro demonstrate that the 120s loop is flexible. Our work suggests that binding at this site prevents a conformational rearrangement of the NS2B region of the protein, which is required for activation. Preventing this movement locks the protein into the open, inactive conformation, suggesting that this site may be useful in the future development of therapeutic allosteric inhibitors. PMID:24164286

  7. O-glycosylation in hinge region of mouse immunoglobulin G2b.

    PubMed

    Kim, H; Yamaguchi, Y; Masuda, K; Matsunaga, C; Yamamoto, K; Irimura, T; Takahashi, N; Kato, K; Arata, Y

    1994-04-22

    Mouse monoclonal immunoglobulin G2b (IgG2b) antibodies are known to contain two forms of the heavy chain that are different in susceptibility to the protease attack. In the present study, by use of an affinity column containing sialic acid-binding lectins from Maackia amurensis seeds, a mouse monoclonal IgG2b was successfully separated into three phenotypes, which are different in the degree of sialylation in the heavy chain. In the N-linked oligosaccharides from all of the IgG2b phenotypes, virtually no sialylation was detected. Elution profiles of the lysyl endopeptidase digestion products were compared for the three phenotypes. The peptides eluted at different retention times were subjected to fast atom bombardment-mass spectrometry and amino acid sequence analyses. It was revealed that approximately 40% of the heavy chain of the mouse IgG2b are O-glycosylated at Thr-221A in the hinge region, predominantly with a tetrasaccharide composed of GalNAc, Gal, and two N-glycolylneuraminic acid residues. We suggest that the O-glycosylation renders the hinge region resistant against the proteolyses of the heavy chain. A therapeutic significance of the O-glycosylation of IgG2b is briefly discussed. PMID:7512967

  8. Histone demethylase KDM2B regulates lineage commitment in normal and malignant hematopoiesis

    PubMed Central

    Andricovich, Jaclyn; Kai, Yan; Peng, Weiqun; Foudi, Adlen; Tzatsos, Alexandros

    2016-01-01

    The development of the hematopoietic system is a dynamic process that is controlled by the interplay between transcriptional and epigenetic networks to determine cellular identity. These networks are critical for lineage specification and are frequently dysregulated in leukemias. Here, we identified histone demethylase KDM2B as a critical regulator of definitive hematopoiesis and lineage commitment of murine hematopoietic stem and progenitor cells (HSPCs). RNA sequencing of Kdm2b-null HSPCs and genome-wide ChIP studies in human leukemias revealed that KDM2B cooperates with polycomb and trithorax complexes to regulate differentiation, lineage choice, cytokine signaling, and cell cycle. Furthermore, we demonstrated that KDM2B exhibits a dichotomous role in hematopoietic malignancies. Specifically, we determined that KDM2B maintains lymphoid leukemias, but restrains RAS-driven myeloid transformation. Our study reveals that KDM2B is an important mediator of hematopoietic cell development and has opposing roles in tumor progression that are dependent on cellular context. PMID:26808549

  9. Sh3pxd2b mice are a model for craniofacial dysmorphology and otitis media.

    PubMed

    Yang, Bin; Tian, Cong; Zhang, Zhi-guang; Han, Feng-chan; Azem, Rami; Yu, Heping; Zheng, Ye; Jin, Ge; Arnold, James E; Zheng, Qing Y

    2011-01-01

    Craniofacial defects that occur through gene mutation during development increase vulnerability to eustachian tube dysfunction. These defects can lead to an increased incidence of otitis media. We examined the effects of a mutation in the Sh3pxd2b gene (Sh3pxd2b(nee)) on the progression of otitis media and hearing impairment at various developmental stages. We found that all mice that had the Sh3pxd2b(nee) mutation went on to develop craniofacial dysmorphologies and subsequently otitis media, by as early as 11 days of age. We found noteworthy changes in cilia and goblet cells of the middle ear mucosa in Sh3pxd2b(nee) mutant mice using scanning electronic microscopy. By measuring craniofacial dimensions, we determined for the first time in an animal model that this mouse has altered eustachian tube morphology consistent with a more horizontal position of the eustachian tube. All mutants were found to have hearing impairment. Expression of TNF-α and TLR2, which correlates with inflammation in otitis media, was up-regulated in the ears of mutant mice when examined by immunohistochemistry and semi-quantitative RT-PCR. The mouse model with a mutation in the Sh3pxd2b gene (Sh3pxd2b(nee)) mirrors craniofacial dysmorphology and otitis media in humans. PMID:21818352

  10. Histone demethylase KDM2B regulates lineage commitment in normal and malignant hematopoiesis.

    PubMed

    Andricovich, Jaclyn; Kai, Yan; Peng, Weiqun; Foudi, Adlen; Tzatsos, Alexandros

    2016-03-01

    The development of the hematopoietic system is a dynamic process that is controlled by the interplay between transcriptional and epigenetic networks to determine cellular identity. These networks are critical for lineage specification and are frequently dysregulated in leukemias. Here, we identified histone demethylase KDM2B as a critical regulator of definitive hematopoiesis and lineage commitment of murine hematopoietic stem and progenitor cells (HSPCs). RNA sequencing of Kdm2b-null HSPCs and genome-wide ChIP studies in human leukemias revealed that KDM2B cooperates with polycomb and trithorax complexes to regulate differentiation, lineage choice, cytokine signaling, and cell cycle. Furthermore, we demonstrated that KDM2B exhibits a dichotomous role in hematopoietic malignancies. Specifically, we determined that KDM2B maintains lymphoid leukemias, but restrains RAS-driven myeloid transformation. Our study reveals that KDM2B is an important mediator of hematopoietic cell development and has opposing roles in tumor progression that are dependent on cellular context. PMID:26808549

  11. Autoinhibition of Escherichia coli Rep monomer helicase activity by its 2B subdomain

    PubMed Central

    Brendza, Katherine M.; Cheng, Wei; Fischer, Christopher J.; Chesnik, Marla A.; Niedziela-Majka, Anita; Lohman, Timothy M.

    2005-01-01

    DNA helicases catalyze separation of double-helical DNA into its complementary single strands, a process essential for DNA replication, recombination, and repair. The Escherichia coli Rep protein, a superfamily 1 DNA helicase, functions in DNA replication restart and is required for replication of several bacteriophages. Monomers of Rep do not display helicase activity in vitro; in fact, DNA unwinding requires Rep dimerization. Here we show that removal of the 2B subdomain of Rep to form RepΔ2B activates monomer helicase activity, albeit with limited processivity. Although both full length Rep and RepΔ2B monomers can translocate with 3′ to 5′ directionality along single-stranded DNA, the 2B subdomain inhibits the helicase activity of full length Rep. This suggests an autoregulatory mechanism for Rep helicase, which may apply to other nonhexameric helicases, whereby helicase activity is regulated by the rotational conformational state of the 2B subdomain; formation of a Rep dimer may relieve autoinhibition by altering the 2B subdomain orientation. PMID:16009938

  12. Autoinhibition of Escherichia coli Rep monomer helicase activity by its 2B subdomain.

    PubMed

    Brendza, Katherine M; Cheng, Wei; Fischer, Christopher J; Chesnik, Marla A; Niedziela-Majka, Anita; Lohman, Timothy M

    2005-07-19

    DNA helicases catalyze separation of double-helical DNA into its complementary single strands, a process essential for DNA replication, recombination, and repair. The Escherichia coli Rep protein, a superfamily 1 DNA helicase, functions in DNA replication restart and is required for replication of several bacteriophages. Monomers of Rep do not display helicase activity in vitro; in fact, DNA unwinding requires Rep dimerization. Here we show that removal of the 2B subdomain of Rep to form RepDelta2B activates monomer helicase activity, albeit with limited processivity. Although both full length Rep and RepDelta2B monomers can translocate with 3' to 5' directionality along single-stranded DNA, the 2B subdomain inhibits the helicase activity of full length Rep. This suggests an autoregulatory mechanism for Rep helicase, which may apply to other nonhexameric helicases, whereby helicase activity is regulated by the rotational conformational state of the 2B subdomain; formation of a Rep dimer may relieve autoinhibition by altering the 2B subdomain orientation. PMID:16009938

  13. Deletion of ADORA2B from myeloid cells dampens lung fibrosis and pulmonary hypertension.

    PubMed

    Karmouty-Quintana, Harry; Philip, Kemly; Acero, Luis F; Chen, Ning-Yuan; Weng, Tingting; Molina, Jose G; Luo, Fayong; Davies, Jonathan; Le, Ngoc-Bao; Bunge, Isabelle; Volcik, Kelly A; Le, Thanh-Thuy T; Johnston, Richard A; Xia, Yang; Eltzschig, Holger K; Blackburn, Michael R

    2015-01-01

    Idiopathic pulmonary fibrosis (IPF) is a lethal, fibroproliferative disease. Pulmonary hypertension (PH) can develop secondary to IPF and increase mortality. Alternatively, activated macrophages (AAMs) contribute to the pathogenesis of both IPF and PH. Here we hypothesized that adenosine signaling through the ADORA2B on AAMs impacts the progression of these disorders and that conditional deletion of ADORA2B on myeloid cells would have a beneficial effect in a model of these diseases. Conditional knockout mice lacking ADORA2B on myeloid cells (Adora2B(f/f)-LysM(Cre)) were exposed to the fibrotic agent bleomycin (BLM; 0.035 U/g body weight, i.p.). At 14, 17, 21, 25, or 33 d after exposure, SpO2, bronchoalveolar lavage fluid (BALF), and histologic analyses were performed. On day 33, lung function and cardiovascular analyses were determined. Markers for AAM and mediators of fibrosis and PH were assessed. Adora2B(f/f)-LysM(Cre) mice presented with attenuated fibrosis, improved lung function, and no evidence of PH compared with control mice exposed to BLM. These findings were accompanied by reduced expression of CD206 and arginase-1, markers for AAMs. A 10-fold reduction in IL-6 and a 5-fold decrease in hyaluronan, both linked to lung fibrosis and PH, were also observed. These data suggest that activation of the ADORA2B on macrophages plays an active role in the pathogenesis of lung fibrosis and PH. PMID:25318478

  14. Ein mobiler und offener Kernspintomograph: Kernspintomographie für Medizin und Materialforschung

    NASA Astrophysics Data System (ADS)

    Blümich, Bernhard; Kölker, Christian; Casanova, Federico; Perlo, Juan; Felder, Jörg

    2005-09-01

    An der RWTH Aachen wurde der erste offene und mobile Kernspintomograph entwickelt. Anders als die normalerweise riesigen und unbeweglichen Geräte besitzt er keine enge Magnetröhre. So kann er auch in große Untersuchungsobjekte hinein schauen, ohne dass diese zerstört werden müssen. Wie eine Lupe erfasst er dabei ein begrenztes Volumen um den Aufsatzpunkt herum. Neben der Medizin ermöglicht der offene Tomograph viele neue Anwendungsgebiete, vor allem in der Materialprüfung und Qualitätskontrolle. Der Aachener Prototyp kann auch das Fließprofil und die Geschwindigkeitsverteilung strömender Flüssigkeiten sichtbar machen. Sein offenes Prinzip erforderte neue technische Komponenten und modifizierte bildgebende Verfahren. Die Messzeit pro Bild kann heute schon unter einer Viertelstunde liegen.

  15. Collisional Removal of O2(b1Σ ^+g, v = 1) by Atomic Oxygen

    NASA Astrophysics Data System (ADS)

    Kalogerakis, K. S.; Pejaković, D. A.; Copeland, R. A.; Slanger, T. G.

    2004-12-01

    In the thermosphere, energy transfer between excited O atoms and ground-state molecular oxygen produces O2 in the first two vibrational levels of the b1Σ ^+g state: O(1D) + O2 -> O(3P) + O2(b1Σ ^+g, v = 0, 1). Subsequent radiative decay of O2(b1Σ ^+g, v = 0, 1) to the ground state O2(X3Σ ^-g) results in the Atmospheric Band emissions. Atmospheric observations suggest that above ˜120 km O(3P) plays an important role in removing O2(b1Σ ^+g, v = 1). Therefore, knowledge of the rate coefficient for collisional removal of O2(b1Σ ^+g<, v = 1) by O(3P) is important for detailed understanding of the Atmospheric Band emissions. Measurements are reported of the room-temperature rate coefficient for removal of O2(b1Σ ^+g, v = 1) by O(3P). A commercial F2 laser with pulsed energy output of up to 50 mJ at 157 nm is used to photodissociate a large fraction of molecular oxygen in a O2/N2 mixture. Photodissociation of an O2 molecule produces a ground-state oxygen atom O(3P) and an excited oxygen atom O(1D), and O(1D) rapidly transfers energy to the remaining O2 to produce O2(b1Σ ^+g, v = 0, 1). The O2(b1Σ ^+g, v = 1) population is monitored by observing emission in the O2 (b-X) 1--1 band at 771 nm. To extract the O2(b1Σ ^+g, v = 1) + O(3P) rate coefficient, knowledge of the O(3P) partial pressure or, equivalently, the fraction of dissociated O2, is necessary. Based on the F2 laser fluence, the signal dependence on the fraction of dissociation, and computer modeling, the signals measured in our experiments correspond to about 50% dissociation. Our measurements yield a preliminary value of the rate coefficient for O2(b1Σ ^+g, v = 1) removal by O(3P) of 6 × 10-12 cm3s-1. The results will be compared to the rate coefficients for corresponding processes in the ground and a1Δ g states of O2, and implications of the results for modeling of the upper atmosphere will be discussed. This work is supported by the NSF Aeronomy Program under grant ATM-0209229. The F2 laser was

  16. Z-Shaped Pyrrolo[3,2-b]pyrroles and Their Transformation into π-Expanded Indolo[3,2-b]indoles.

    PubMed

    Stężycki, Rafał; Grzybowski, Marek; Clermont, Guillaume; Blanchard-Desce, Mireille; Gryko, Daniel T

    2016-04-01

    Sterically hindered 1,4-dihydropyrrolo[3,2-b]pyrroles possessing ortho-(arylethynyl)phenyl substituents at positions-2 and -5 were efficiently synthesized through a sila-Sonogashira reaction. These unique Z-shaped dyes showed relatively strong fluorescence in solution. Detailed optimization revealed that, in the presence of InCl3, these alkynes readily undergo an intramolecular double cyclization to give hexacyclic products bearing an indolo[3,2-b]indole skeleton in remarkable yields. Steady-state UV-visible spectroscopy revealed that upon photoexcitation, the prepared Z-shaped alkynes undergo mostly radiative relaxation leading to high fluorescence quantum yields. In the case of 7,14-dihydrobenzo[g]benzo[6,7]indolo[3,2-b]indoles, we believe that the substantial planarization of geometry in the excited state, is the underlying reason for the observed large Stokes shifts. The presence of additional electron-withdrawing groups makes it possible to further alter the photophysical properties. The two-photon absorption cross-section values of both families of dyes were found to be modest and the nature of the excited state responsible for two-photon absorption appeared to be strongly affected by the presence of peripheral groups. Serendipitous synthesis of unusual double-Z-shaped alkyne by Sonogashira and Glaser coupling is also reported. PMID:26889746

  17. Increased extrasynaptic GluN2B expression is involved in cognitive impairment after isoflurane anesthesia

    PubMed Central

    LI, LUNXU; LI, ZHENGQIAN; CAO, YIYUN; FAN, DONGSHENG; CHUI, DEHUA; GUO, XIANGYANG

    2016-01-01

    There is increasing concern regarding the postoperative cognitive dysfunction (POCD) in the aging population, and general anesthetics are believed to be involved. Isoflurane exposure induced increased N-methyl-D-aspartic acid receptor (NMDAR) GluN2B subunit expression following anesthesia, which was accompanied by alteration of the cognitive function. However, whether isoflurane affects this expression in different subcellular compartments, and is involved in the development of POCD remains to be elucidated. The aims of the study were to investigate the effects of isoflurane on the expression of the synaptic and extrasynaptic NMDAR subunits, GluN2A and GluN2B, as well as the associated alteration of cognitive function in aged rats. The GluN2B antagonist, Ro25–6981, was given to rats exposed to isoflurane to determine the role of GluN2B in the isoflurane-induced alteration of cognitive function. The results showed that spatial learning and memory tested in the Morris water maze (MWM) was impaired at least 7 days after isoflurane exposure, and was returned to control levels 30 days thereafter. Ro25-6981 treatment can alleviate this impairment. Extrasynaptic GluN2B protein expression, but not synaptic GluN2B or GluN2A, increased significantly after isoflurane exposure compared to non-isoflurane exposure, and returned to control levels approximately 30 days thereafter. The results of the present study indicated that isoflurane induced the prolonged upregulation of extrasynaptic GluN2B expression after anesthesia and is involved in reversible cognitive impairment. PMID:27347033

  18. Complex Alternative Splicing of the Smarca2 Gene Suggests the Importance of Smarca2-B Variants

    PubMed Central

    Yang, Min; Sun, Yuan; Ma, Ling; Wang, Chenguang; Wu, Jian-min; Bi, Anding; Liao, D. Joshua

    2011-01-01

    BRM is an ATPase component of the SWI/SNF complex that regulates chromatin remodeling and cell proliferation and is considered a tumor suppressor. In this study we characterized transcripts from the Smarca2 gene that encodes the BRM protein. We found that the human Smarca2 gene (hSmarca2), like its mouse counterpart (mSmarca2), also initiated a short transcript from intron 27 of the long transcript. We name the long and short transcripts as Smarca2-a and Smarca2-b, respectively. Like its human counterpart, mSmarca2-a also underwent alternative splicing at the 54-bp exon 29. The hSmarca2-b had two alternative initiation sites and underwent alternative splicing at three different 3' sites of exon 1 and at exons 2, 3 and/or 5. We identified nine hSmarca2-b mRNA variants that might produce five different proteins. mSmarca2-b also underwent alternative splicing at exon 3 and/or exon 5, besides alternatively retaining part of intron 1 in exon 1. Smarca2-b was expressed more abundantly than Smarca2-a in many cell lines and was more sensitive to serum starvation. Moreover, cyclin D1 also regulated the expression of both Smarca2-a and Smarca2-b in a complex manner. These data suggest that the functions of the Smarca2 gene may be very complex, not just simply inhibiting cell proliferation, and in certain situations may be elicited mainly by expressing the much less known Smarca2-b, not the better studied Smarca2-a and its products BRM proteins. PMID:21811517

  19. Polycrystalline TiO2 (B) Nanosheet Films Deposited via Langmuir-Blodgett Method

    NASA Astrophysics Data System (ADS)

    Biedermann, Laura; Kotula, Paul; Beechem, Thomas; Dylla, Anthony; Stevenson, Keith; Chan, Calvin

    2014-03-01

    As an energy storage material, TiO2 offers higher Li+ capacities and smaller volume changes with lithiation than graphite electrodes. In particular, the bronze phase, TiO2(B) has a higher lithiation capacity (1.0 Li+/Ti) and faster lithiation kinetics due to its larger lattice parameters than other TiO2 polymorphs. Direct observation of lithiation will require TiO2(B) monolayers, such as those prepared via Langmuir-Blodgett deposition of the nanosheets (NS). Optical microscopy of the TiO2(B)-NS Langmuir monolayer at the air/water interface shows that these nanosheets assemble into large (>1 mm) islands. These elastic TiO2(B)-NS monolayers are deposited on diverse substrates for further characterization. Electron diffraction in both transmission electron microscopy (TEM) and low-energy electron microscopy (LEEM) of these films confirm that their polycrystalline structure is predominately composed of TiO2(B) nanocrystals, ~10s nm across. Discrimination of monolayer and bilayer TiO2(B) is evident in LEEM. Thermal stability of these nanosheets is investigated via in-situ TEM and ex-situ Raman spectroscopy. This monolayer TiO2(B) deposition will allow future observations of lithiation and phase changes. Sandia is managed by Sandia Corp., a subsidiary Lockheed Martin, for the U.S. DOE NNSA (DE-AC04-94AL85000). Work was supported by an U.S. DOE BES EFRC (DE-SC0001091).

  20. Regulation of Postsynaptic Function by the Dementia-Related ESCRT-III Subunit CHMP2B

    PubMed Central

    Chassefeyre, Romain; Martínez-Hernández, José; Bertaso, Federica; Bouquier, Nathalie; Blot, Béatrice; Laporte, Marine; Fraboulet, Sandrine; Couté, Yohann; Devoy, Anny; Isaacs, Adrian M.; Pernet-Gallay, Karin; Fagni, Laurent

    2015-01-01

    The charged multivesicular body proteins (Chmp1–7) are an evolutionarily conserved family of cytosolic proteins that transiently assembles into helical polymers that change the curvature of cellular membrane domains. Mutations in human CHMP2B cause frontotemporal dementia, suggesting that this protein may normally control some neuron-specific process. Here, we examined the function, localization, and interactions of neuronal Chmp2b. The protein was highly expressed in mouse brain and could be readily detected in neuronal dendrites and spines. Depletion of endogenous Chmp2b reduced dendritic branching of cultured hippocampal neurons, decreased excitatory synapse density in vitro and in vivo, and abolished activity-induced spine enlargement and synaptic potentiation. To understand the synaptic effects of Chmp2b, we determined its ultrastructural distribution by quantitative immuno-electron microscopy and its biochemical interactions by coimmunoprecipitation and mass spectrometry. In the hippocampus in situ, a subset of neuronal Chmp2b was shown to concentrate beneath the perisynaptic membrane of dendritic spines. In synaptoneurosome lysates, Chmp2b was stably bound to a large complex containing other members of the Chmp family, as well as postsynaptic scaffolds. The supramolecular Chmp assembly detected here corresponds to a stable form of the endosomal sorting complex required for transport-III (ESCRT-III), a ubiquitous cytoplasmic protein complex known to play a central role in remodeling of lipid membranes. We conclude that Chmp2b-containing ESCRT-III complexes are also present at dendritic spines, where they regulate synaptic plasticity. We propose that synaptic ESCRT-III filaments may function as a novel element of the submembrane cytoskeleton of spines. PMID:25698751

  1. Conditional loss of GluN2B in cortex and hippocampus impairs attentional set formation

    PubMed Central

    Thompson, Shannon M.; Josey, Megan; Holmes, Andrew; Brigman, Jonathan L.

    2015-01-01

    The ability to attend to appropriate stimuli, to plan actions and then alter those actions when environmental conditions change, is essential for an organism to thrive. There is increasing evidence that these executive control processes are mediated in part by N-methyl-D-aspartate receptors (NMDAR). NMDAR subunits confer different physiological properties to the receptor, interact with distinct intracellular postsynaptic scaffolding and signaling molecules and are differentially expressed during development. Recent findings have suggested that the GluN2B subunit may play a unique role in both the acquisition of adaptive choice and the behavioral flexibility required to shift between choices. Here we investigated the role of GluN2B containing NMDARs in the ability to learn, reverse and shift between stimulus dimensions. Mutant mice (floxed-GluN2B x CaMKII-Cre) lacking GluN2B in the dorsal CA1 of the hippocampus and throughout the cortex were tested on an attentional set-shifting task. To explore the role that alterations in motor behavior may have on these behaviors, gross and fine motor behaviors were analyzed in mutant and floxed-control mice. Results show that corticohippocampal loss of GluN2B selectively impaired an initial reversal in a stimulus specific manner and impaired the ability of mutant mice to form an attentional set. Further, GluN2B mice showed normal motor behavior in both overall movement and individual limb behaviors. Together, these results further support the role of NMDAR, and GluN2B in particular, in aspects of executive control including behavioral flexibility and attentional processes. PMID:25798630

  2. An i2b2-based, generalizable, open source, self-scaling chronic disease registry

    PubMed Central

    Quan, Justin; Ortiz, David M; Bousvaros, Athos; Ilowite, Norman T; Inman, Christi J; Marsolo, Keith; McMurry, Andrew J; Sandborg, Christy I; Schanberg, Laura E; Wallace, Carol A; Warren, Robert W; Weber, Griffin M; Mandl, Kenneth D

    2013-01-01

    Objective Registries are a well-established mechanism for obtaining high quality, disease-specific data, but are often highly project-specific in their design, implementation, and policies for data use. In contrast to the conventional model of centralized data contribution, warehousing, and control, we design a self-scaling registry technology for collaborative data sharing, based upon the widely adopted Integrating Biology & the Bedside (i2b2) data warehousing framework and the Shared Health Research Information Network (SHRINE) peer-to-peer networking software. Materials and methods Focusing our design around creation of a scalable solution for collaboration within multi-site disease registries, we leverage the i2b2 and SHRINE open source software to create a modular, ontology-based, federated infrastructure that provides research investigators full ownership and access to their contributed data while supporting permissioned yet robust data sharing. We accomplish these objectives via web services supporting peer-group overlays, group-aware data aggregation, and administrative functions. Results The 56-site Childhood Arthritis & Rheumatology Research Alliance (CARRA) Registry and 3-site Harvard Inflammatory Bowel Diseases Longitudinal Data Repository now utilize i2b2 self-scaling registry technology (i2b2-SSR). This platform, extensible to federation of multiple projects within and between research networks, encompasses >6000 subjects at sites throughout the USA. Discussion We utilize the i2b2-SSR platform to minimize technical barriers to collaboration while enabling fine-grained control over data sharing. Conclusions The implementation of i2b2-SSR for the multi-site, multi-stakeholder CARRA Registry has established a digital infrastructure for community-driven research data sharing in pediatric rheumatology in the USA. We envision i2b2-SSR as a scalable, reusable solution facilitating interdisciplinary research across diseases. PMID:22733975

  3. Functional characterization of a type 2 metallothionein isoform (OsMTI-2b) from rice.

    PubMed

    Pirzadeh, Soheil; Shahpiri, Azar

    2016-07-01

    Metallothioneins (MTs) are a family of Cys-rich, low molecular weight, cytoplasmic metal binding proteins. MTs are present in all eukaryotes as well as some prokaryotes. Plant MTs are divided into four types based on Cys distribution pattern in their amino acid sequences. In the present work, the gene encoding OsMTI-2b, a type 2 MT found in rice, was cloned into pET41a vector. The resulting construct was transformed into Escherichia coli strain Rosetta (DE3). Following the induction with Isopropyl β-d-1-thiogalactopyranoside the OsMTI-2b was expressed as carboxyl-terminal extensions of glutathione-S-transferase (GST-tag), a 6His-tag, and an S-tag. The expressed recombinant fusion protein was named GST-OsMTI-2b. As compared with control, transgenic E. coli cells expressing GST-OsMTI-2b accumulated more Pb(2+), Ni(2+), Cd(2+), Zn(2+) and Cu(2+) from culture medium and showed increased tolerance against these metals. Furthermore the E. coli cells expressing OsMTI-2b accumulated significantly higher Pb(2+) than previously made strains which expressing other rice OsMT isoforms. The recombinant GST-OsMTI-2b was purified using affinity chromatography. According to in vitro assays the protein GST-OsMTI-2b was able to form complexes with Pb(2+), Ni(2+), Cd(2+) and Zn(2+). However, the binding ability for the different metals differed in the order: Pb(2+)>Cd(2+)>Zn(2+)>Ni(2+). PMID:27079330

  4. The CaMKII/GluN2B Protein Interaction Maintains Synaptic Strength.

    PubMed

    Barcomb, Kelsey; Hell, Johannes W; Benke, Tim A; Bayer, K Ulrich

    2016-07-29

    Learning, memory, and cognition are thought to require normal long-term potentiation (LTP) of synaptic strength, which in turn requires binding of the Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) to the NMDA-type glutamate receptor (NMDAR) subunit GluN2B. For LTP induction, many additional required players are known. Here we tested the hypothesis that CaMKII/GluN2B binding also mediates the more elusive maintenance of synaptic strength. Intriguingly, the CaMKII inhibitor tatCN21 reduces synaptic strength only at high concentrations necessary for CaMKII/NMDAR disruption (20 μm) but not at lower concentrations sufficient for kinase inhibition (5 μm). However, increased concentration also causes unrelated effects. Thus, to distinguish between correlation and causality, we used a pharmacogenetic approach. In a mouse with a mutant NMDAR GluN2B subunit that is CaMKII binding-incompetent, any tatCN21 effects that are specific to the CaMKII/GluN2B interaction should be abolished, and any remaining tatCN21 effects have to be nonspecific (i.e. mediated by other targets). The results showed that the persistent reduction of synaptic strength by transient application of 20 μm tatCN21 had a nonspecific presynaptic component (on fiber volley amplitude) that was unrelated to the CaMKII/GluN2B interaction or CaMKII activity. However, the remaining component of the persistent tatCN21 effect was almost completely abolished in the GluN2B mutant mouse. These results highlight the requirement for stringent pharmacogenetic approaches to separate specific on-target effects from nonspecific off-target effects. Importantly, they also demonstrate that the CaMKII/GluN2B interaction is required not only for normal LTP induction but also for the maintenance of synaptic strength. PMID:27246855

  5. Serotonin Receptors and Heart Valve Disease – it was meant 2B

    PubMed Central

    Hutcheson, Joshua D.; Setola, Vincent; Roth, Bryan L.; Merryman, W. David

    2011-01-01

    Carcinoid heart disease was one of the first valvular pathologies studied in molecular detail, and early research identified serotonin produced by oncogenic enterochromaffin cells as the likely culprit in causing changes in heart valve tissue. Researchers and physicians in the mid-1960s noted a connection between the use of several ergot-derived medications with structures similar to serotonin and the development of heart valve pathologies similar to those observed in carcinoid patients. The exact serotonergic target that mediated valvular pathogenesis remained a mystery for many years until similar cases were reported in patients using the popular diet drug Fen-Phen in the late 1990s. The Fen-Phen episode sparked renewed interest in serotonin-mediated valve disease, and studies led to the identification of the 5-HT2B receptor as the likely molecular target leading to heart valve tissue fibrosis. Subsequent studies have identified numerous other activators of the 5-HT2B receptor, and consequently, the use of many of these molecules has been linked to heart valve disease. Herein, we: review the molecular properties of the 5-HT2B receptor including factors that differentiate the 5-HT2B receptor from other 5-HT receptor subtypes, discuss the studies that led to the identification of the 5-HT2B receptor as the mediator of heart valve disease, present current efforts to identify potential valvulopathogens by screening for 5-HT2B receptor activity, and speculate on potential therapeutic benefits of 5-HT2B receptor targeting. PMID:21440001

  6. Antigenic Determinants of Possible Vaccine Escape by Porcine Circovirus Subtype 2b Viruses

    PubMed Central

    Constans, Megan; Ssemadaali, Marvin; Kolyvushko, Oleksandr; Ramamoorthy, Sheela

    2015-01-01

    Currently available commercial vaccines against porcine circovirus strain 2 (PCV2) solely target the PCV2a genotype. While PCV2 vaccines are highly effective in preventing clinical signs, PCV2b has dominated over the PCV2a genotype in prevalence, corresponding with the introduction of PCV2a vaccines. A recently emerged PCV2b recombinant with an additional amino acid in the capsid protein, designated the mutant PCV2b (mPCV2b), is cause for concern due to its increased virulence and rapid spread. The accumulation of recent evidence for the increased genetic diversity in PCV2 suggests that current vaccines against PCV2a may be inducing selection pressure and driving viral evolution. In this study, the hypothesis that differences in key immune epitopes between the PCV2a vaccine strains, a classical PCV2b strain called PCV2b 41513 obtained from a vaccine-failure case, and mPCV2b strains could promote vaccine escape was tested using immuno-informatic tools. In the major viral proteins, 9 of the 18 predicted swine leukocyte antigens (SLA) class-I epitopes, 8 of the 22 predicted SLA class-II epitopes, and 7 of the 25 predicted B cell epitopes varied between the vaccine and field strains. A majority of the substitutions in both the T- and B-cell epitopes were located in the capsid protein. Some B- and T-cell epitopes that were identified as immunogenic in the vaccine strain were not identified as epitopes in the field strains, indicating a subtle shift in the antigenic profile of the field strains. Several nonconserved epitopes had both predicted B- and T-cell functions. Therefore, substitutions in the dual epitopes could affect both arms of the immune response simultaneously, causing immune escape. Our findings support further rational design of PCV2 vaccines to increase the current threshold of protection. PMID:26339187

  7. Anreicherung von Webinhalten mit Semantik - Microformats und RDFa

    NASA Astrophysics Data System (ADS)

    Hausenblas, Michael

    Semantik in Webinhalten wird heftig diskutiert. Teilweise wird es auch schon praktiziert. Dieser Beitrag geht auf semantisches HTML, Microformats und RDFa näher ein und zeigt anhand von praktischen Beispielen, wie und wo diese verwendet werden können.

  8. Tycho Brahe - Instrumentenbauer und Meister der Beobachtungstechnik

    NASA Astrophysics Data System (ADS)

    Wolfschmidt, Gudrun

    Vor der Erfindung des Fernrohrs war der dänische Astronom Tycho Brahe (1546 - 1601) der bedeutendste beobachtende Astronom. Von seinem Observatorium Uraniborg auf der - damals dänischen - Insel Hven ist heute noch der Grundriß erkennbar, von Stjerneborg sind die Fundamente erhalten, die Kuppeln in den 1950er Jahren ergänzt. In der Astronomie-Ausstellung im Deutschen Museum gibt es ein Modell der Sternwarte Uraniborg und der zugehörigen Instrumente (Maßstab 1:10); das größere Modell wurde dem Technischen Museum in Malmö geschenkt. Die Instrumente, die er in den Observatorien Uraniborg und Stjerneborg benutzte, sind nicht erhalten. Aber es gibt gute Beschreibungen der Instrumente (Halbkreis, Quadranten, Sextanten, Armillarsphären, Triquetrum, Himmelsglobus) in seinem Buch Astronomiae instauratae mechanica (Wandsbek 1598). Eine Nachbildung des großen hölzernen Quadranten kann man im Runden Turm in Kopenhagen sehen. Zwei Sextanten, hergestellt für Tycho um 1600 von Jost Bürgi und Erasmus Habermel, gibt es noch im Nationalmuseum für Technik in Prag. Ähnlichkeiten von Tychos Instrumenten mit Groß-Instrumenten aus dem islamischen Kulturkreis sind auffällig. Tycho Brahes Meßgeräte markieren einen großen Fortschritt in der Entwicklung astronomischer Instrumente und Meßtechniken und bilden die Grundlage für den weiteren Fortschritt der Positionsastronomie und der damit verbundenen Tabellenwerke. Die Nachwirkungen sind bis ins 17. und 18. Jahrhundert nachweisbar.

  9. The Expression of Tubb2b Undergoes a Developmental Transition in Murine Cortical Neurons.

    PubMed

    Breuss, Martin; Morandell, Jasmin; Nimpf, Simon; Gstrein, Thomas; Lauwers, Mattias; Hochstoeger, Tobias; Braun, Andreas; Chan, Kelvin; Sánchez Guajardo, Edmundo R; Zhang, Lijuan; Suplata, Marek; Heinze, Katrin G; Elsayad, Kareem; Keays, David A

    2015-10-15

    The development of the mammalian brain requires the generation, migration, and differentiation of neurons, cellular processes that are dependent on a dynamic microtubule cytoskeleton. Mutations in tubulin genes, which encode for the structural subunits of microtubules, cause detrimental neurological disorders known as the tubulinopathies. The disease spectra associated with different tubulin genes are overlapping but distinct, an observation believed to reflect functional specification of this multigene family. Perturbation of the β-tubulin TUBB2B is known to cause polymicrogyria, pachygyria, microcephaly, and axon guidance defects. Here we provide a detailed analysis of the expression pattern of its murine homolog Tubb2b. The generation and characterization of BAC-transgenic eGFP reporter mouse lines has revealed that it is highly expressed in progenitors and postmitotic neurons during cortical development. This contrasts with the 8-week-old cortex, in which Tubb2b expression is restricted to macroglia, and expression is almost completely absent in mature neurons. This developmental transition in neurons is mirrored in the adult hippocampus and the cerebellum but is not a universal feature of Tubb2b; its expression persists in a population of postmitotic neurons in the 8-week-old retina. We propose that the dynamic spatial and temporal expression of Tubb2b reflects specific functional requirements of the microtubule cytoskeleton. PMID:26105993

  10. 5-HT2B Receptor Antagonists Inhibit Fibrosis and Protect from RV Heart Failure

    PubMed Central

    Janssen, Wiebke; Schymura, Yves; Novoyatleva, Tatyana; Luitel, Himal; Tretyn, Aleksandra; Pullamsetti, Soni Savai; Weissmann, Norbert; Seeger, Werner; Ghofrani, Hossein Ardeschir; Schermuly, Ralph Theo

    2015-01-01

    Objective. The serotonin (5-HT) pathway was shown to play a role in pulmonary hypertension (PH), but its functions in right ventricular failure (RVF) remain poorly understood. The aim of the current study was to investigate the effects of Terguride (5-HT2A and 2B receptor antagonist) or SB204741 (5-HT2B receptor antagonist) on right heart function and structure upon pulmonary artery banding (PAB) in mice. Methods. Seven days after PAB, mice were treated for 14 days with Terguride (0.2 mg/kg bid) or SB204741 (5 mg/kg day). Right heart function and remodeling were assessed by right heart catheterization, magnetic resonance imaging (MRI), and histomorphometric methods. Total secreted collagen content was determined in mouse cardiac fibroblasts isolated from RV tissues. Results. Chronic treatment with Terguride or SB204741 reduced right ventricular fibrosis and showed improved heart function in mice after PAB. Moreover, 5-HT2B receptor antagonists diminished TGF-beta1 induced collagen synthesis of RV cardiac fibroblasts in vitro. Conclusion. 5-HT2B receptor antagonists reduce collagen deposition, thereby inhibiting right ventricular fibrosis. Chronic treatment prevented the development and progression of pressure overload-induced RVF in mice. Thus, 5-HT2B receptor antagonists represent a valuable novel therapeutic approach for RVF. PMID:25667920

  11. MiR-448 promotes glycolytic metabolism of gastric cancer by downregulating KDM2B

    PubMed Central

    Zhu, Yuekun; Feng, Xing; Ding, Zhijie; Zhang, Shifeng; Zhong, Lifeng; Zhuang, Yifan; Su, Chen; Hong, Xinya; Cai, Jianchun

    2016-01-01

    MicroRNAs are critical in various human cancers, including gastric cancer (GC). However, the mechanism underlying the GC development remains elusive. In this study, we demonstrate that miR-448 is increased in GC samples and cell lines. Overexpression of miR-448 facilitated the proliferation of GC cells by stimulating glycolysis. Mechanistically, we identified KDM2B, a reader for methylated CpGs, as the target of miR-448 that represses glycolysis and promotes oxidative phosphorylation. Overexpression of miR-448 reduced both the mRNA and protein levels of KDM2B, whereas KDM2B re-expression abrogated the miR-448-mediated glycolytic activities. Furthermore, we discovered Myc as a key target of KDM2B that controls metabolic switch in GC. Importantly, a cohort of 81 GC tissues revealed that miR-448 level closely associated with a battery of glycolytic genes, in which KDM2B showed the strongest anti-correlation coefficient. In addition, enhanced miR-448 level was significantly associated with poor clinical outcomes of GC patients. Hence, we identified a previously unappreciated mechanism by which miR-448 orchestrate epigenetic, transcriptional and metabolic networks to promote GC progression, suggesting the possibility of therapeutic intervention against cancer metabolic pathways. PMID:26989077

  12. Localization of sulfonylurea receptor subunits, SUR2A and SUR2B, in rat heart.

    PubMed

    Zhou, Ming; He, Hui-Jing; Suzuki, Ryoji; Liu, Ke-Xiang; Tanaka, Osamu; Sekiguchi, Masaki; Itoh, Hideaki; Kawahara, Katsumasa; Abe, Hiroshi

    2007-08-01

    To understand the possible functions and subcellular localizations of sulfonylurea receptors (SURs) in cardiac muscle, polyclonal anti-SUR2A and anti-SUR2B antisera were raised. Immunoblots revealed both SUR2A and SUR2B expression in mitochondrial fractions of rat heart and other cellular fractions such as microsomes and cell membranes. Immunostaining detected ubiquitous expression of both SUR2A and SUR2B in rat heart in the atria, ventricles, interatrial and interventricular septa, and smooth muscles and endothelia of the coronary arteries. Electron microscopy revealed SUR2A immunoreactivity in the cell membrane, endoplasmic reticulum (ER), and mitochondria. SUR2B immunoreactivity was mainly localized in the mitochondria as well as in the ER and cell membrane. Thus, SUR2A and SUR2B are not only the regulatory subunits of sarcolemmal K(ATP) channels but may also function as regulatory subunits in mitochondrial K(ATP) channels and play important roles in cardioprotection. PMID:17438353

  13. Scintigraphic portrayal of the syndrome of multiple endocrine neoplasia type-2B

    SciTech Connect

    Yobbagy, J.J.; Levatter, R.; Sisson, J.C.; Shulkin, B.L.; Polley, T.

    1988-06-01

    The scintigraphic appearance of the neoplasms in multiple endocrine neoplasia type 2B (MEN-2B) and the interpretations of the image patterns are described. An 18-year-old male patient with the MEN-2B syndrome underwent TI-201 imaging that showed concentrations of TI-201 in the primary medullary thyroid carcinoma (MTC) tumor and in cervical lymph node metastases. After total thyroidectomy and lymph node dissection, the TI-201 image was normal. Catecholamine levels in the blood and urine were only borderline elevated. Yet, greater than normal concentrations of I-131 metaiodobenzylguanidine (I-131 MIBG) were present in both adrenal glands. Computed tomography of the abdomen showed normal adrenal glands. These results were consistent with the diagnosis of adrenal medullary hyperplasia, a precursor of pheochromocytoma. No operation was indicated to remove the adrenal glands. Imaging with TI-201 appears to be useful in identifying sites of MTC in patients with the MEN-2B syndrome. I-131 MIBG imaging, in conjunction with computed tomography of the adrenal glands and appropriate catecholamine measurements, should be performed in patients with the MEN-2B syndrome to determine the status of the adrenal medullae, which then may be classified as normal, hyperplastic, or tumorous with pheochromocytoma.

  14. Synthesis and TL characterization of Li2B4O7 doped with copper and manganese

    NASA Astrophysics Data System (ADS)

    Guarneros-Aguilar, C.; Cruz-Zaragoza, E.; Marcazzó, J.; Palomino-Merino, R.; Espinosa, J. E.

    2013-07-01

    Copper (Cu) and manganese (Mn) doped tissue equivalent Li2B4O7 were prepared by solid state sintering. The glow curves shows a high temperature peak at 222 °C for Li2B4O7:Cu and for Li2B4O7:Mn at 218 °C. Linear dose response is observed up to 140 Gy. With a thermal treatment at 125 °C, the first peak of the phosphors doped with copper (95 °C) and manganese (90 °C) disappears and the main TL peaks remain isolated. The dose rate dependence was studied by exposing the samples at doses of 25 Gy and 250 Gy. At low dose it was observed that the Li2B4O7:Cu TL response has non-dependence on dose rate, and at higher dose was observed that there is a dependence of the TL response with the different dose rate until of 30%. For the case of Li2B4O7:Mn, the TL response has non-dependence on dose rate at low dose or high dose.

  15. Immunodiagnosis of tumors in vivo using radiolabeled monoclonal antibody A2B5

    SciTech Connect

    Reintgen, D.S.; Shimizu, K.; Coleman, E.; Briner, W.; Kitzmiller, J.; Eisenbarth, G.; Seigler, H.F.

    1983-07-01

    Recently a murine monoclonal antibody (A2B5) has been described that reacts with a membrane associated GQ ganglioside common to peptide secreting normal cells and tumors. In vitro binding data demonstrated the presence of this ganglioside on neurons, adrenal medulla, and pancreatic islets, along with neuroendocrine tumors such as insulinomas, pheochromocytomas, melanomas and neuroblastomas. Negative binding has previously been shown for tissue sections from liver, kidney, colon, lung, stomach, and tumors not derived from the neural crest. Because of the specificity at A2B5 in vitro, this monoclonal antibody was labeled with /sup 131/I for in vivo tumor localization studies. Daily radionuclear scans were obtained in 5 KX rats bearing the radiation induced rat insulinoma with disappearance of the label from the blood pool and concentration in the tumor so that by the fourth day, the only activity present by scan was in the insulinoma. In addition A2B5 also localized to five different human melanoma cells lines grown in nude mice with high tumor/blood levels compared to normal tissues, while no localization is seen in nudes carrying osteosarcomas, colon, bladder, and renal cell carcinomas. In addition antibody A2B5 did not concentrate in any normal tissue though the antigen is present on several. The finding that A2B5 reacts across species lines (mouse, rat, man) lends itself to obvious diagnostic and therapeutic possibilities.

  16. Supporting the Health Quality Measures Format in i2b2.

    PubMed

    Klann, Jeffrey G; Murphy, Shawn N

    2013-01-01

    The Health Quality Measures Format (HQMF) is an HL7 standard for expressing computable queries of clinical data. It is becoming increasingly consequential for both quality measurement and population health research. A variety of national leadership is involved in its development and deployment, including the Meaningful Use incentive program, the Query Health initiative, the Joint Commission, the National Quality Forum (NQF), and the Food and Drug Administration. Here we analyze the structure of HQMF and apply this to computation of HQMF on Informatics for Integrating Biology and the Bedside (i2b2). i2b2 is a widely used, modular, open-source clinical research data repository. We implement a translator to convert between HQMF and i2b2-XML format that covers the subset of HQMF supported in i2b2-XML, which will be expanded in the next release of i2b2. This translator is part of the freely-available reference implementation of the QueryHealth initiative. PMID:24303250

  17. Effects of nano bamboo charcoal on PAHs-degrading strain Sphingomonas sp. GY2B.

    PubMed

    She, Bojia; Tao, Xueqin; Huang, Ting; Lu, Guining; Zhou, Zhili; Guo, Chuling; Dang, Zhi

    2016-03-01

    Nano bamboo charcoal (NBC) has been commonly used in the production of textiles, plastics, paint, etc. However, little is known regarding their effects towards the microorganisms. The effects of NBC on phenanthrene degrading strain Sphingomonas sp. GY2B were investigated in the present study. Results showed that the addition of NBC could improve the phenanthrene removal by Sphingomonas sp. GY2B, with removal efficiencies increased by 10.29-18.56% in comparison to the control at 24h, and phenanthrene was almost completely removed at 48h. With the presence of low dose of NBC (20 and 50mgL(-1)), strain GY2B displayed a better growth at 6h, suggesting that NBC was beneficial to the growth of GY2B and thus resulting in the quick removal of phenanthrene from water. However, the growth of strain GY2B in high dose of NBC (200mgL(-1)) was inhibited at 6h, and the inhibition could be attenuated and eliminated after 12h. NBC-effected phenanthrene solubility experiment suggested that NBC makes a negligible contribution to the solubilization of phenanthrene in water. Results of electronic microscopy analysis (SEM and TEM) indicated NBC may interact with the cell membrane, causing the enhanced membrane permeability and then NBC adsorbed on the membrane would enter into the cells. The findings of this work would provide important information for the future usage and long-term environmental risk assessment of NBC. PMID:26655231

  18. GluN2B in corticostriatal circuits governs choice learning and choice shifting

    PubMed Central

    Brigman, Jonathan L.; Daut, Rachel; Wright, Tara; Gunduz-Cinar, Ozge; Graybeal, Carolyn; Davis, Margaret I.; Jiang, Zhihong; Saksida, Lisa; Jinde, Seiichiro; Pease, Matthew; Bussey, Timothy J.; Lovinger, David M.; Nakazawa, Kazu; Holmes, Andrew

    2013-01-01

    A choice that reliably produces a preferred outcome can be automated to liberate cognitive resources for other tasks. Should an outcome become less desirable, behavior must adapt in parallel or become perseverative. Corticostriatal systems are known to mediate choice learning and flexibility, but the molecular mechanisms subserving the instantiation of these processes are not well understood. We integrated mouse behavioral, immunocytochemical, in vivo electrophysiological, genetic, and pharmacological approaches to study choice. We found that the dorsal striatum (DS) was increasingly activated with choice learning, whereas reversal of learned choice engaged prefrontal regions. In vivo, DS neurons showed activity associated with reward anticipation and receipt that emerged with learning and relearning. Corticostriatal or striatal GluN2B gene deletion, or DS-restricted GluN2B antagonism, impaired choice learning, whereas cortical GluN2B deletion or OFC GluN2B antagonism impaired shifting. Our convergent data demonstrate how corticostriatal GluN2B circuits govern the ability to learn and shift choice behavior. PMID:23831965

  19. Glucagon regulates gluconeogenesis through KAT2B- and WDR5-mediated epigenetic effects

    PubMed Central

    Ravnskjaer, Kim; Hogan, Meghan F.; Lackey, Denise; Tora, Laszlo; Dent, Sharon Y.R.; Olefsky, Jerrold; Montminy, Marc

    2013-01-01

    Circulating pancreatic glucagon is increased during fasting and maintains glucose balance by stimulating hepatic gluconeogenesis. Glucagon triggering of the cAMP pathway upregulates the gluconeogenic program through the phosphorylation of cAMP response element–binding protein (CREB) and the dephosphorylation of the CREB coactivator CRTC2. Hormonal and nutrient signals are also thought to modulate gluconeogenic gene expression by promoting epigenetic changes that facilitate assembly of the transcriptional machinery. However, the nature of these modifications is unclear. Using mouse models and in vitro assays, we show that histone H3 acetylation at Lys 9 (H3K9Ac) was elevated over gluconeogenic genes and contributed to increased hepatic glucose production during fasting and in diabetes. Dephosphorylation of CRTC2 promoted increased H3K9Ac through recruitment of the lysine acetyltransferase 2B (KAT2B) and WD repeat–containing protein 5 (WDR5), a core subunit of histone methyltransferase (HMT) complexes. KAT2B and WDR5 stimulated the gluconeogenic program through a self-reinforcing cycle, whereby increases in H3K9Ac further potentiated CRTC2 occupancy at CREB binding sites. Depletion of KAT2B or WDR5 decreased gluconeogenic gene expression, consequently breaking the cycle. Administration of a small-molecule KAT2B antagonist lowered circulating blood glucose concentrations in insulin resistance, suggesting that this enzyme may be a useful target for diabetes treatment. PMID:24051374

  20. Binding and cytotoxicity characteristics of the bispecific murine monoclonal antibody 2B1.

    PubMed

    Weiner, L M; Holmes, M; Richeson, A; Godwin, A; Adams, G P; Hsieh-Ma, S T; Ring, D B; Alpaugh, R K

    1993-09-01

    Bispecific monoclonal antibodies (BsmAb) with specificity for tumor Ag and effector cell trigger molecules have been shown to redirect the cytotoxicity of several peripheral blood mononuclear cell populations against relevant tumor. The BsmAb, 2B1, binds to the extracellular domain of the c-erbB-2 gene product of the HER2/neu proto-oncogene and to CD16. In this report, the binding and cytotoxic characteristics of 2B1 are presented. Maximal saturation binding of 2B1 to PBL and c-erbB-2 expressing SK-OV-3 cells occurred in the 1 microgram/ml concentration range. However, substantial lysis potentiation was observed at 1000-fold lower BsmAb concentrations. Optimal tumor lysis was obtained when the BsmAb, PBL, and target cells were continuously coincubated. When PBL were franked with 2B1, washed, and added to labeled targets, substantially less lysis was observed. These results suggest that the best way to therapeutically exploit the cytotoxic attributes of 2B1 may be to obtain continuous BsmAb exposure to tumor. Approaches based on franking of this BsmAb to PBL may not be warranted. PMID:8103070

  1. Thermal, magnetic and electronic properties of non-centrosymmetric YbPt2B

    NASA Astrophysics Data System (ADS)

    Khan, R. T.; Kneidinger, F.; Hilscher, G.; Sidorenko, A.; Sologub, O.; Michor, H.; Bauer, E.; Rogl, P.; Giester, G.

    2015-04-01

    Ternary YbPt2B crystallizes in the non-centrosymmetric hexagonal CePt2B-type structure (space group P6222). Electrical resistivity, specific heat and magnetic measurements reveal a magnetic instability at 5.6 K. Furthermore, a spin-reorientation of presumably a ferromagnetic type occurs around 1.5 K. The behaviour at low temperature is governed by a rather weak Kondo effect, TK ⩽ 1 K, in the presence of strong crystalline electric field splitting, with a doublet ground state. Besides, the complex magnetic behaviour presumably results from a Dzyaloshinskii-Moriya interaction triggered by the absence of inversion symmetry in the crystal structure. Scaling according to the de Gennes factor traces back magnetic ordering in YbPt2B to the Rudermann-Kittel-Kasuya-Yoshida (RKKY) interaction and the smooth evolution of the lattice constants and the unit cell volume of REPt2B (RE = rare earths) refers to the 4f13 electronic configuration of Yb in YbPt2B.

  2. Morphology diagrams for A2B copolymer melts: real-space self-consistent field theory

    SciTech Connect

    Kumar, Rajeev; Sides, Scott; Mays, Jimmy; Li, Yige; Sumpter, Bobby G

    2012-01-01

    Morphology diagrams for A2B copolymer melts are constructed using real-space self-consistent field theory (SCFT). In particular, the effect of architectural asymmetry on the morphology diagram is studied. It is shown that asymmetry in the lengths of A arms in the A2B copolymer melts aids in the microphase separation. As a result, the disorder-order transition boundaries for the A2B copolymer melts are shown to shift downward in terms of N, and N being the Flory s chi parameter and the total number of the Kuhn segments,respectively, in comparison with the A2B copolymers containing symmetric A arms. Furthermore, perforated lamellar (PL) and a micelle-like (M) microphase segregated morphologies are found to compete with the classical morphologies namely, lamellar, cylinders, spheres and gyroid. The PL morphology is found to be stable for A2B copolymers containing asymmetric A arms and M is found to be metastable for the parameter range explored in this work.

  3. Benzimidazolone bioisosteres of potent GluN2B selective NMDA receptor antagonists.

    PubMed

    Lütnant, Ines; Schepmann, Dirk; Wünsch, Bernhard

    2016-06-30

    Overactivation of the NMDA receptor is associated with excitotoxic events leading to neurodegenerative processes as observed during the development of Alzheimer's disease, ParFnson's disease, Chorea Huntington and epilepsy. Negative allosteric modulators addressing selectively the ifenprodil binding site of GluN2B subunit containing NMDA receptors are of major interest due to their neuroprotective potential accompanied by few side effects. Herein benzimidazolone bioisosteres of potent GluN2B antagonists 1-5 were designed and synthesized. A seven step sequence provided the central intermediate 19 in 28% yield. Elimination of water, methylation, epoxidation, epoxide rearrangement and finally reductive amination afforded the [7]annulenobenzimidazolone 30 with a 3-phenylpropylamino substituent in 6-position. Although 30 fits nicely into the pharmacophore of potent GluN2B antagonists, the gluN2B binding affinity of 30 was only moderate (Ki = 697 nM). Additionally, 30 shows low selectivity over the σ2 receptor (Ki = 549 nM). The moderate GluN2B affinity was explained by the rigid tricyclic structure of the [7]annulenobenzimidazolone 30. PMID:27061977

  4. Identification of the Pro orientation of CAP2b peptides for antidiuretic activity in the stink bug Acrosternum hilare

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The CAP2b neuropeptide family plays an important role in the regulation of the processes of diuresis and/or antidiuresis in a variety of insects. While Manse-CAP2b (pELYAFPRVamide) and native CAP2bs elicit diuretic activity in a number of species of flies, native CAP2b sequences have been shown to ...

  5. Molecular and functional characterization of the first tick CAP2b (periviscerokinin) receptor from Rhipicephalus (Boophilus) microplus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The cDNA of the receptor for CAP2b/periviscerokinin (PVK) neuropeptides, designated Rhimi-CAP2b-R, was cloned from synganglia of tick Rhipicephalus (Boophilus) microplus. This receptor is the ortholog of the insect CAP2b/PVK receptor, as concluded from analyses of the predicted protein sequence, ph...

  6. 78 FR 24047 - Wage Methodology for the Temporary Non-Agricultural Employment H-2B Program, Part 2

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-24

    ... regulations DOL issued on February 21, 2012, (77 FR 10038) (2012 H-2B rule) implementing its consultative... challenge to DOL's rulemaking authority with respect to an H-2B wage rule issued on January 19, 2011 (76 FR... are not adversely affected by the use of H-2B workers. See 55 FR 2606, 2617 (Jan. 26, 1990)....

  7. 26 CFR 301.6103(p)(2)(B)-1 - Disclosure of returns and return information by other agencies.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... other agencies. 301.6103(p)(2)(B)-1 Section 301.6103(p)(2)(B)-1 Internal Revenue INTERNAL REVENUE... Information and Returns Returns and Records § 301.6103(p)(2)(B)-1 Disclosure of returns and return information... regulations thereunder, including, if applicable, safeguards imposed by section 6103(p)(4). (d) Records...

  8. 26 CFR 301.6103(p)(2)(B)-1 - Disclosure of returns and return information by other agencies.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... other agencies. 301.6103(p)(2)(B)-1 Section 301.6103(p)(2)(B)-1 Internal Revenue INTERNAL REVENUE... Information and Returns Returns and Records § 301.6103(p)(2)(B)-1 Disclosure of returns and return information... regulations thereunder, including, if applicable, safeguards imposed by section 6103(p)(4). (d) Records...

  9. 26 CFR 301.6103(p)(2)(B)-1 - Disclosure of returns and return information by other agencies.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... other agencies. 301.6103(p)(2)(B)-1 Section 301.6103(p)(2)(B)-1 Internal Revenue INTERNAL REVENUE... Information and Returns Returns and Records § 301.6103(p)(2)(B)-1 Disclosure of returns and return information... regulations thereunder, including, if applicable, safeguards imposed by section 6103(p)(4). (d) Records...

  10. 26 CFR 301.6103(p)(2)(B)-1 - Disclosure of returns and return information by other agencies.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... other agencies. 301.6103(p)(2)(B)-1 Section 301.6103(p)(2)(B)-1 Internal Revenue INTERNAL REVENUE... Information and Returns Returns and Records § 301.6103(p)(2)(B)-1 Disclosure of returns and return information... regulations thereunder, including, if applicable, safeguards imposed by section 6103(p)(4). (d) Records...

  11. 26 CFR 301.6103(p)(2)(B)-1 - Disclosure of returns and return information by other agencies.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... other agencies. 301.6103(p)(2)(B)-1 Section 301.6103(p)(2)(B)-1 Internal Revenue INTERNAL REVENUE... Information and Returns Returns and Records § 301.6103(p)(2)(B)-1 Disclosure of returns and return information... regulations thereunder, including, if applicable, safeguards imposed by section 6103(p)(4). (d) Records...

  12. 76 FR 2930 - International Product Change-Global Plus 1B and 2B Negotiated Service Agreements

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-01-18

    ... Product Change--Global Plus 1B and 2B Negotiated Service Agreements AGENCY: Postal Service \\TM\\. ACTION... add Global Plus 1B and 2B Negotiated Service Agreements to the Competitive Products List pursuant to... Service to Add Global Plus 1B and 2B Negotiated Service Agreements to the Competitive Product List,...

  13. RNF20 and USP44 regulate stem cell differentiation by modulating H2B monoubiquitylation.

    PubMed

    Fuchs, Gilad; Shema, Efrat; Vesterman, Rita; Kotler, Eran; Wolchinsky, Zohar; Wilder, Sylvia; Golomb, Lior; Pribluda, Ariel; Zhang, Feng; Haj-Yahya, Mahmood; Feldmesser, Ester; Brik, Ashraf; Yu, Xiaochun; Hanna, Jacob; Aberdam, Daniel; Domany, Eytan; Oren, Moshe

    2012-06-01

    Embryonic stem cells (ESCs) maintain high genomic plasticity, which is essential for their capacity to enter diverse differentiation pathways. Posttranscriptional modifications of chromatin histones play a pivotal role in maintaining this plasticity. We now report that one such modification, monoubiquitylation of histone H2B on lysine 120 (H2Bub1), catalyzed by the E3 ligase RNF20, increases during ESC differentiation and is required for efficient execution of this process. This increase is particularly important for the transcriptional induction of relatively long genes during ESC differentiation. Furthermore, we identify the deubiquitinase USP44 as a negative regulator of H2B ubiquitylation, whose downregulation during ESC differentiation contributes to the increase in H2Bub1. Our findings suggest that optimal ESC differentiation requires dynamic changes in H2B ubiquitylation patterns, which must occur in a timely and well-coordinated manner. PMID:22681888

  14. Crystal structure and physical properties of Mo{sub 2}B: First-principle calculations

    SciTech Connect

    Zhou, Dan; Cui, Qiliang E-mail: liquan777@jlu.edu.cn; Li, Quan E-mail: liquan777@jlu.edu.cn; Wang, Jingshu

    2014-03-21

    Several decades ago, Mo{sub 2}B was assumed to have an Al{sub 2}Cu-type structure with I4/mcm space group. Using ab initio phonon calculations, we identify the earlier proposed Al{sub 2}Cu-type structure is dynamically unstable at ambient pressure. An energetically more favorable phase with the tetragonal I4/m structure was then predicted by employing frozen-phonon technique. The currently predicted I4/m phase is mechanically and dynamically stable and energetically more favorable than that of the earlier proposed Al{sub 2}Cu-type structure. The electronic structures calculations indicate that Mo{sub 2}B is a metal with several bands crossing the Fermi level. Our analysis indicates that the three-dimensional network of the covalent Mo-B bond is responsible for the ultra-incompressible property of Mo{sub 2}B.

  15. Synthesis of Mg2B2O5 whiskers via coprecipitation and sintering process

    NASA Astrophysics Data System (ADS)

    Zhu, Dong-hai; Nai, Xue-ying; Zhu, Cheng-cai; Guo, Feng-qin; Bian, Shao-ju; Li, Wu

    2012-10-01

    Mg2B2O5 whiskers with high aspect ratio were synthesized by coprecipitation and sintering process using MgCl2·6H2O, H3BO3, and NaOH as raw materials and KCl as a flux. Their formation process was investigated by thermogravimetry and differential scanning calorimetry (TG-DSC), X-ray diffraction (XRD), and scanning electron microcopy (SEM). It is found that the products synthesized at 832°C are monoclinic Mg2B2O5 whiskers with a diameter of 200-400 nm and a length of 50-80 μm. Transmission electron microscopy (TEM) and selected area electron diffraction (SAED) analyses show that the whiskers obtained at 832°C are single crystalline and grow along with the [010] direction. The growth mechanism of Mg2B2O5 whiskers was also presented.

  16. A POPULATION-SPECIFIC HTR2B STOP CODON PREDISPOSES TO SEVERE IMPULSIVITY

    PubMed Central

    Bevilacqua, Laura; Doly, Stéphane; Kaprio, Jaakko; Yuan, Qiaoping; Tikkanen, Roope; Paunio, Tiina; Zhou, Zhifeng; Wedenoja, Juho; Maroteaux, Luc; Diaz, Silvina; Belmer, Arnaud; Hodgkinson, Colin A.; Dell’Osso, Liliana; Suvisaari, Jaana; Coccaro, Emil; Rose, Richard J; Peltonen, Leena; Virkkunen, Matti; Goldman, David

    2011-01-01

    SUMMARY Impulsivity, describing action without foresight, is an important feature of several psychiatric diseases, suicidality and violent behavior. The complex origins of impulsivity hinder identification of the genes influencing both it and diseases with which it is associated. We performed exon-centric sequencing of impulsive individuals in a founder population, targeting fourteen genes belonging to the serotonin and dopamine domain. A stop codon in HTR2B that is common (MAF >1%) but exclusive to Finns was identified. Expression of the gene in the human brain was assessed, as well as the molecular functionality of the stop codon that was associated with psychiatric diseases marked by impulsivity in both population and family-based analyses. Knockout of Htr2b increased impulsive behaviors in mice, indicative of predictive validity. Our study shows the potential for identifying and tracing effects of rare alleles in complex behavioral phenotypes using founder populations, and suggests a role for HTR2B in impulsivity. PMID:21179162

  17. A new natural naphtho[1,2-b]furan from the leaves of Cassia fistula.

    PubMed

    Wang, Li-Qin; Tang, Zheng-Rong; Mu, Wei-Hua; Kou, Jun-Feng; He, Dong-Yang

    2013-11-01

    A new naphtho[1,2-b]furan, 2,9-dihydroxy-7-methoxy-4-methylnaphtha[1,2-b]furan-3(2H)-one (1), along with 10 known compounds vanillic acid (2), naringenin (3), glyceryl-1-tetracosanoate (4), moracin J (5), 1,3,8-trihydroxyanthraquinone (6), esculetin (7), mauritianin (8), kaempferol 3-neohesperidoside (9), β-sitosterol (10), and β-daucosterol (11), was isolated from the leaves of Cassia fistula. The structure of the new compound was determined by NMR and X-ray analysis. Compounds 1, 3, 5-9 were isolated from this plant for the first time. The naphtha[1,2-b]furan was firstly isolated from the natural resources. PMID:23822190

  18. Regulation of α2B-Adrenerigc Receptor Export Trafficking by Specific Motifs

    PubMed Central

    Wu, Guangyu; Davis, Jason E.; Zhang, Maoxiang

    2016-01-01

    Intracellular trafficking and precise targeting to specific locations of G protein-coupled receptors (GPCRs) control the physiological functions of the receptors. Compared to the extensive efforts dedicated to understanding the events involved in the endocytic and recycling pathways, the molecular mechanisms underlying the transport of the GPCR superfamily from the endoplasmic reticulum (ER) through the Golgi to the plasma membrane are relatively less well defined. Over the past years, we have used α2B-adrenergic receptor (α2B-AR) as a model to define the factors that control GPCR export trafficking. In this chapter, we will review specific motifs identified to mediate the export of nascent α2B-AR from the ER and the Golgi and discuss the possible underlying mechanisms. As these motifs are highly conserved among GPCRs, they may provide common mechanisms for export trafficking of these receptors. PMID:26055061

  19. Severe osteoporosis due to systemic mast cell disease: successful treatment with interferon alpha-2B.

    PubMed

    Lehmann, T; Beyeler, C; Lämmle, B; Hunziker, T; Vock, P; Olah, A J; Dahinden, C; Gerber, N J

    1996-09-01

    We describe a 33-year old man suffering from severe vertebral osteoporosis and urticaria pigmentosa due to systemic mast cell disease (SMCD). Because i.v. clodronate therapy could not prevent further vertebral fractures, an additional treatment with interferon alpha-2b was initiated. During 24 months of treatment, our patient had no further pain episodes, no new vertebral fractures were discovered, trabecular bone mineral density (BMD) increased significantly and urticarial symptoms improved. Nevertheless, the extent of skin lesions remained unchanged. On histological examination, a remarkable decrease of mast cells was observed in the bone marrow, but not in the skin. Five months after discontinuation of interferon alpha-2b, trabecular BMD decreased and urticarial symptoms deteriorated. These findings illustrate a beneficial effect of interferon alpha-2b on SMCD-induced osteoporosis as well as urticarial symptoms, and raise the question whether this treatment may have a diverse impact on mast cell population in different tissues. PMID:8810675

  20. Supporting Multi-sourced Medication Information in i2b2

    PubMed Central

    Klann, Jeffrey G.; Pfiffner, Pascal B.; Natter, Marc D.; Conner, Emily; Blazejewski, Paul; Murphy, Shawn N.; Mandl, Kenneth D.

    2015-01-01

    Postmarketing drug surveillance is critical to assessing adverse events associated with medications, because prelaunch clinical trials frequently miss negative drug effects. The Informatics for Integrating Biology and the Bedside platform (i2b2) has been used effectively for this. However, previous work suffers from incomplete medical data present in electronic health record (EHR) systems. Here, we develop a system to integrate non-traditional data sources with EHR data: pharmacy dispensing information and patient-reported data. We implement and validate a toolset to gather medication data from a Pharmacy Benefit Manager network, import it into an i2b2 EHR repository using a standard data format, merge it with the EHR data, and present it to for annotation with results returned to i2b2. This toolkit is enabling studies on medication list data quality, adherence, and adverse event detection. PMID:26958210

  1. Superconductivity and magnetism in (Ho xY 1- x)Ni 2B 2C

    NASA Astrophysics Data System (ADS)

    Eversmann, K.; Handstein, A.; Fuchs, G.; Cao, L.; Müller, K.-H.

    1996-02-01

    Superconducting and magnetic properties of polycrystalline samples of the pseudoquarternary system (Ho xY 1- x)Ni 2B 2C have been investigated by resistance and susceptibility measurements. A linear depression of the superconducting transition temperature with increasing magnetic ordering temperatures was found by variation of the Ho content providing evidence for magnetic pair breaking. This behaviour is analogous to the known scaling with the de Gennes factor of the rare earth elements in the family of quaternary RNi 2B 2C compounds. Both cases are described by a common scaling behaviour including the superconducting and magnetic transition temperatures. A reetrrant behaviour observed for Ho contents x>0.5 results in maximum in the temperature dependence of the upper critical field Hc2( T). These results are compared with Hc2( T) data of the RNi 2B 2C family ( R=Tm,Er).

  2. Superconductivity in RNi 2B 2C (R = rare earth) compounds

    NASA Astrophysics Data System (ADS)

    Tomy, C. V.; Chang, L. J.; Balakrishnan, G.; Paul, D. M. c.K.

    1994-12-01

    A series of compounds in the recently discovered RNi 2B 2C family of superconductors have been prepared in order to investigate their magnetic and transport properties. Compounds of the form (Y 1-xA x)Ni 2B 2C (A=Sm,Dy) were examined to study the effects of magnetic pair breaking. Resistance measurements show that the lighter rare earth Sm depresses T c faster than the heavier rare earth Dy. Solid solutions of the type (Er 1-xHo x)Ni 2B 2C have also been studied for the possible coexistence of superconductivity and magnetism in these compounds. Even though the magnetic ordering of the rare earth moments can be deduced from our susceptibility measurements, resistance measurements showed no reetrant behavior in any of these compounds down to 1.2 K.

  3. Leitbilder und Handlungsstrategien für die Raumentwicklung in Deutschland. Entwicklungs-, Umsetzungs- und Fortschreibungsprozess der Bund-Länder-Strategie für Städte und Regionen

    NASA Astrophysics Data System (ADS)

    Issaoui, Mariam; Sinz, Manfred

    2010-09-01

    Die Ministerkonferenz für Raumordnung stellte im Mai 2010 fest, dass sich die „Leitbilder und Handlungsstrategien für die Raumentwicklung in Deutschland“ (2006) bewährt haben und bei der Gestaltung der räumlichen Entwicklung umgesetzt werden. Um die Leitbilder den sich verändernden wirtschaftlichen, sozialen und naturräumlichen Rahmenbedingungen anzupassen und die Erkenntnisse aus dem bisherigen Diskussions- und Umsetzungsprozess in Politik und Praxis einzubeziehen, sind sie zu ergänzen und weiterzuentwickeln. Im Mittelpunkt der Fortschreibung werden die Themen „Partnerschaften und Strategien für Stadtregionen und ländliche Räume“, „Mobilität und Logistik“ sowie „Klimaschutz und Energieversorgung“ stehen.

  4. Oral application of freeze-dried yeast particles expressing the PCV2b Cap protein on their surface induce protection to subsequent PCV2b challenge in vivo

    PubMed Central

    Patterson, Robert; Eley, Thomas; Browne, Christopher; Martineau, Henny M.; Werling, Dirk

    2015-01-01

    Porcine circovirus type 2 (PCV2) is now endemic in every major pig producing country, causing PCV-associated disease (PCVAD), linked with large scale economic losses. Current vaccination strategies are based on the capsid protein of the virus and are reasonably successful in preventing PCVAD but fail to induce sterile immunity. Additionally, vaccinating whole herds is expensive and time consuming. In the present study a “proof of concept” vaccine trial was employed to test the effectiveness of powdered freeze-dried recombinant Saccharomyces cerevisiae yeast stably expressing the capsid protein of PCV2b on its surface as an orally applied vaccine. PCV2-free pigs were given 3 doses of vaccine or left un-vaccinated before challenge with a defined PCV2b strain. Rectal temperatures were measured and serum and faeces samples were collected weekly. At the end of the study, pigs were euthanized, tissue samples taken and tested for PCV2b load by qPCR and immunohistochemistry. The peak of viraemia in sera and faeces of unvaccinated pigs was higher than that of vaccinated pigs. Additionally more sIgA was found in faeces of vaccinated pigs than unvaccinated. Vaccination was associated with lower serum concentrations of TNFα and IL-1β but higher concentrations of IFNα and IFNγ in comparison to the unvaccinated animals. At the end of the trial, a higher viral load was found in several lymphatic tissues and the ileum of unvaccinated pigs in comparison to vaccinated pigs. The difference between groups was especially apparent in the ileum. The results presented here demonstrate a possible use for recombinant S. cerevisiae expressing viral proteins as an oral vaccine against PCV2. A powdered freeze-dried recombinant S. cerevisiae used as an oral vaccine could be mixed with feed and may offer a cheap and less labour intensive alternative to inoculation with the additional advantage that no cooling chain would be required for vaccine transport and storage. PMID:26476879

  5. Oral application of freeze-dried yeast particles expressing the PCV2b Cap protein on their surface induce protection to subsequent PCV2b challenge in vivo.

    PubMed

    Patterson, Robert; Eley, Thomas; Browne, Christopher; Martineau, Henny M; Werling, Dirk

    2015-11-17

    Porcine circovirus type 2 (PCV2) is now endemic in every major pig producing country, causing PCV-associated disease (PCVAD), linked with large scale economic losses. Current vaccination strategies are based on the capsid protein of the virus and are reasonably successful in preventing PCVAD but fail to induce sterile immunity. Additionally, vaccinating whole herds is expensive and time consuming. In the present study a "proof of concept" vaccine trial was employed to test the effectiveness of powdered freeze-dried recombinant Saccharomyces cerevisiae yeast stably expressing the capsid protein of PCV2b on its surface as an orally applied vaccine. PCV2-free pigs were given 3 doses of vaccine or left un-vaccinated before challenge with a defined PCV2b strain. Rectal temperatures were measured and serum and faeces samples were collected weekly. At the end of the study, pigs were euthanized, tissue samples taken and tested for PCV2b load by qPCR and immunohistochemistry. The peak of viraemia in sera and faeces of unvaccinated pigs was higher than that of vaccinated pigs. Additionally more sIgA was found in faeces of vaccinated pigs than unvaccinated. Vaccination was associated with lower serum concentrations of TNFα and IL-1β but higher concentrations of IFNα and IFNγ in comparison to the unvaccinated animals. At the end of the trial, a higher viral load was found in several lymphatic tissues and the ileum of unvaccinated pigs in comparison to vaccinated pigs. The difference between groups was especially apparent in the ileum. The results presented here demonstrate a possible use for recombinant S. cerevisiae expressing viral proteins as an oral vaccine against PCV2. A powdered freeze-dried recombinant S. cerevisiae used as an oral vaccine could be mixed with feed and may offer a cheap and less labour intensive alternative to inoculation with the additional advantage that no cooling chain would be required for vaccine transport and storage. PMID:26476879

  6. Structural Basis for Host Membrane Remodeling Induced by Protein 2B of Hepatitis A Virus

    PubMed Central

    Vives-Adrián, Laia; Garriga, Damià; Buxaderas, Mònica; Fraga, Joana; Pereira, Pedro José Barbosa

    2015-01-01

    ABSTRACT The complexity of viral RNA synthesis and the numerous participating factors require a mechanism to topologically coordinate and concentrate these multiple viral and cellular components, ensuring a concerted function. Similarly to all other positive-strand RNA viruses, picornaviruses induce rearrangements of host intracellular membranes to create structures that act as functional scaffolds for genome replication. The membrane-targeting proteins 2B and 2C, their precursor 2BC, and protein 3A appear to be primarily involved in membrane remodeling. Little is known about the structure of these proteins and the mechanisms by which they induce massive membrane remodeling. Here we report the crystal structure of the soluble region of hepatitis A virus (HAV) protein 2B, consisting of two domains: a C-terminal helical bundle preceded by an N-terminally curved five-stranded antiparallel β-sheet that displays striking structural similarity to the β-barrel domain of enteroviral 2A proteins. Moreover, the helicoidal arrangement of the protein molecules in the crystal provides a model for 2B-induced host membrane remodeling during HAV infection. IMPORTANCE No structural information is currently available for the 2B protein of any picornavirus despite it being involved in a critical process in viral factory formation: the rearrangement of host intracellular membranes. Here we present the structure of the soluble domain of the 2B protein of hepatitis A virus (HAV). Its arrangement, both in crystals and in solution under physiological conditions, can help to understand its function and sheds some light on the membrane rearrangement process, a putative target of future antiviral drugs. Moreover, this first structure of a picornaviral 2B protein also unveils a closer evolutionary relationship between the hepatovirus and enterovirus genera within the Picornaviridae family. PMID:25589659

  7. Immunodiagnosis of tumors in vivo using radiolabeled monoclonal antibody A2B5.

    PubMed

    Reintgen, D S; Shimizu, K; Coleman, E; Briner, W; Kitzmiller, J; Eisenbarth, G; Seigler, H F

    1983-07-01

    Recently a murine monoclonal antibody (A2B5) has been described that reacts with a membrane associated GQ ganglioside common to peptide secreting normal cells and tumors. In vitro binding data demonstrated the presence of this ganglioside on neurons, adrenal medulla, and pancreatic islets, along with neuroendocrine tumors such as insulinomas, pheochromocytomas, melanomas and neuroblastomas. Negative binding has previously been shown for tissue sections from liver, kidney, colon, lung, stomach, and tumors not derived from the neural crest. Because of the specificity at A2B5 in vitro, this monoclonal antibody was labeled with 131I for in vivo tumor localization studies. Daily radionuclear scans were obtained in 5 KX rats bearing the radiation induced rat insulinoma with disappearance of the label from the blood pool and concentration in the tumor so that by the fourth day, the only activity present by scan was in the insulinoma. Tissue-counting data showed tumor/blood ratios (av +/- SE, 1.29 +/- 0.25) of A2B5 activity two to ten times the average activity found in other organs (0.28 +/- 0.05). No tumor concentration of the control nonspecific monoclonal antibody P3X63 was evident (0.27 +/- 0.04). In addition A2B5 also localized to five different human melanoma cells lines grown in nude mice with high tumor/blood levels (1.04 +/- 0.27) compared to normal tissues (0.32 +/- 0.05) (P = .0005), while no localization is seen in nudes carrying osteosarcomas, colon, bladder, and renal cell carcinomas. In addition antibody A2B5 did not concentrate in any normal tissue though the antigen is present on several. The finding that A2B5 reacts across species lines (mouse, rat, man) lends itself to obvious diagnostic and therapeutic possibilities. PMID:6306349

  8. Association Study of N-Methyl-D-Aspartate Receptor Subunit 2B (GRIN2B) Polymorphisms and Schizophrenia Symptoms in the Han Chinese Population.

    PubMed

    Yang, Yongfeng; Li, Wenqiang; Zhang, Hongxing; Yang, Ge; Wang, Xiujuan; Ding, Minli; Jiang, Tianzi; Lv, Luxian

    2015-01-01

    Schizophrenia (SZ) is a common and complex psychiatric disorder that has a significant genetic component. The glutamatergic system is the major excitatory neurotransmitter system in the central nervous system, and is mediated by N-methyl-D-aspartate (NMDA) receptors. Disturbances in this system have been hypothesized to play a major role in SZ pathogenesis. Several studies have revealed that the NMDA receptor subunit 2B (GRIN2B) potentially associates with SZ and its psychiatric symptoms. In this study, we performed a case-control study to identify polymorphisms of the GRIN2B gene that may confer susceptibility to SZ in the Han Chinese population. Thirty-four single nucleotide polymorphisms (SNPs) were genotyped in 528 paranoid SZ patients and 528 control subjects. A significant association was observed in allele and genotype between SZ and controls at rs2098469 (χ2 = 8.425 and 4.994; p = 0.025 and 0.014, respectively). Significant associations were found in the allele at rs12319804 (χ2 = 4.436; p = 0.035), as well as in the genotype at rs12820037 and rs7298664 between SZ and controls (χ2 = 11.162 and 38.204; p = 0.003 and 4.27×10(-8), respectively). After applying the Bonferroni correction, rs7298664 still had significant genotype associations with SZ (p = 1.71×10(-7)). In addition, rs2098469 genotype and allele frequencies, and 12820037 allele frequencies were nominally associated with SZ. Three haplotypes, CGA (rs10845849-rs12319804-rs10845851), CC (rs12582848-rs7952915), and AAGAC (rs2041986-rs11055665-rs7314376-rs7297101-rs2098469), had significant differences between SZ and controls (χ2 = 4.324, 4.582, and 4.492; p = 0.037, 0.032, and 0.034, respectively). In addition, three SNPs, rs2098469, rs12820037, and rs7298664, were significantly associated with cognition factors PANSS subscores in SZ (F = 16.799, 7.112, and 13.357; p = 0.000, 0.017, and 0.000, respectively). In conclusion, our study provides novel evidence for an association between GRIN2B

  9. Some crystallography, chemistry, physics, and thermodynamics of B12O2, B12P2, B12As2, and related alpha-boron type crystals

    NASA Astrophysics Data System (ADS)

    Slack, Glen A.; Morgan, Kenneth E.

    2014-09-01

    This paper shows that several alpha-boron type compounds may be useful as high-temperature semiconductors with decent carrier motilities, high electrical resistivity, good optical transparency, good stability under high radiation bombardment, and possess high neutron capture cross-sections. The most promising are B12O2, B12P2, and B12As2. Their relationship to alpha-boron, B13C2, and other derivative crystals is explained. A study of their chemical and thermodynamic properties indicates how single crystals useful for electronic devices can be grown.

  10. Association Study of N-Methyl-D-Aspartate Receptor Subunit 2B (GRIN2B) Polymorphisms and Schizophrenia Symptoms in the Han Chinese Population

    PubMed Central

    Zhang, Hongxing; Yang, Ge; Wang, Xiujuan; Ding, Minli; Jiang, Tianzi; Lv, Luxian

    2015-01-01

    Schizophrenia (SZ) is a common and complex psychiatric disorder that has a significant genetic component. The glutamatergic system is the major excitatory neurotransmitter system in the central nervous system, and is mediated by N-methyl-D-aspartate (NMDA) receptors. Disturbances in this system have been hypothesized to play a major role in SZ pathogenesis. Several studies have revealed that the NMDA receptor subunit 2B (GRIN2B) potentially associates with SZ and its psychiatric symptoms. In this study, we performed a case–control study to identify polymorphisms of the GRIN2B gene that may confer susceptibility to SZ in the Han Chinese population. Thirty-four single nucleotide polymorphisms (SNPs) were genotyped in 528 paranoid SZ patients and 528 control subjects. A significant association was observed in allele and genotype between SZ and controls at rs2098469 (χ2 = 8.425 and 4.994; p = 0.025 and 0.014, respectively). Significant associations were found in the allele at rs12319804 (χ2 = 4.436; p = 0.035), as well as in the genotype at rs12820037 and rs7298664 between SZ and controls (χ2 = 11.162 and 38.204; p = 0.003 and 4.27×10-8, respectively). After applying the Bonferroni correction, rs7298664 still had significant genotype associations with SZ (p = 1.71×10-7). In addition, rs2098469 genotype and allele frequencies, and 12820037 allele frequencies were nominally associated with SZ. Three haplotypes, CGA (rs10845849—rs12319804—rs10845851), CC (rs12582848—rs7952915), and AAGAC (rs2041986—rs11055665—rs7314376—rs7297101—rs2098469), had significant differences between SZ and controls (χ2 = 4.324, 4.582, and 4.492; p = 0.037, 0.032, and 0.034, respectively). In addition, three SNPs, rs2098469, rs12820037, and rs7298664, were significantly associated with cognition factors PANSS subscores in SZ (F = 16.799, 7.112, and 13.357; p = 0.000, 0.017, and 0.000, respectively). In conclusion, our study provides novel evidence for an association between

  11. H-T Phase Diagram of Flux Line Lattice Structure in YNi2B2C

    NASA Astrophysics Data System (ADS)

    Sakiyama, N.; Tsukagoshi, H.; Yano, F.; Nagata, T.; Kawano-Furukawa, H.; Yoshizawa, H.; Yethiraj, M.; Takeya, H.; Suzuki, J.

    2006-09-01

    The detailed flux line lattice (FLL) structure in YNi2B2C was investigated using small angle neutron scattering and the complete H-T phase diagram was determined. The FLL in YNi2B2C shows a change of symmetry only in the low magnetic field region between 0.05 to 0.2 T. The observed square lattice is governed by an anisotropic Fermi velocity. Contrary to the theoretical prediction, a square lattice driven by an anisotropic superconducting gap does not appear below 5 T.

  12. Microwave-assisted synthesis and electrochemical evaluation of VO2 (B) nanostructures.

    PubMed

    Ashton, Thomas E; Hevia Borrás, David; Iadecola, Antonella; Wiaderek, Kamila M; Chupas, Peter J; Chapman, Karena W; Corr, Serena A

    2015-12-01

    Understanding how intercalation materials change during electrochemical operation is paramount to optimizing their behaviour and function and in situ characterization methods allow us to observe these changes without sample destruction. Here we first report the improved intercalation properties of bronze phase vanadium dioxide VO2 (B) prepared by a microwave-assisted route which exhibits a larger electrochemical capacity (232 mAh g(-1)) compared with VO2 (B) prepared by a solvothermal route (197 mAh g(-1)). These electrochemical differences have also been followed using in situ X-ray absorption spectroscopy allowing us to follow oxidation state changes as they occur during battery operation. PMID:26634729

  13. New halogenated tris-(phenylalkyl)amines as h5-HT2B receptor ligands.

    PubMed

    Kapadia, Nirav; Ahmed, Shahrear; Harding, Wayne W

    2016-07-15

    A series of compounds in which various halogen substituents were incorporated into a phenyl ring of a tris-(phenylalkyl)amine scaffold, was synthesized and evaluated for affinity to h5-HT2 receptors. In general, all compounds were found to have good affinity for the 5-HT2B receptor and were selective over 5-HT2A and 5-HT2C receptors. Compound 9i was the most selective compound in this study and is the highest affinity 5-HT2B receptor ligand bearing a tris-(phenylalkyl)amine scaffold to date. PMID:27261181

  14. Magnetic and superconducting phase diagrams in ErNi2B2C

    SciTech Connect

    Galvis, J.A.; Crespo, M.; Guillamon, I.; Suderow, Hermann; Vieira, S.; Garcia Hernandez, M.; Budko, Serguei; Canfield, Paul

    2012-03-30

    We present measurements of the superconducting upper critical field Hc2(T) and the magneticphasediagram of the superconductor ErNi2B2C made with a scanning tunneling microscope (STM). The magnetic field was applied in the basal plane of the tetragonal crystal structure. We have found large gapless regions in the superconductingphasediagram of ErNi2B2C, extending between different magnetic transitions. A close correlation between magnetic transitions and Hc2(T) is found, showing that superconductivity is strongly linked to magnetism.

  15. UGT2B17 copy number gain in a large ankylosing spondylitis multiplex family

    PubMed Central

    2013-01-01

    Background The primary objective of this study is to identify novel copy number variations (CNVs) associated with familial ankylosing spondylitis (AS). A customized genome-wide microarray was designed to detect CNVs and applied to a multiplex AS family with six (6) affected family members. CNVs were detected using the built-in DNA analytics aberration detection method-2 (ADM-2) algorithm. Gene enrichment analysis was performed to observe the segregation. Subsequent validation was performed using real time quantitative fluorescence polymerase reaction (QF-PCR). The frequency of copy number variation for the UGT2B17 gene was then performed on two well-defined AS cohorts. Fisher exact test was performed to quantify the association. Results Our family-based analysis revealed ten gene-enriched CNVs that segregate with all six family members affected with AS. Based on the proposed function and the polymorphic nature of the UGT2B17 gene, the UGT2B17 gene CNV was selected for validation using real time QF-PCR with full concordance. The frequency of two copies of the UGT2B17 gene CNV was 0.41 in the Newfoundland AS cases and 0.35 in the Newfoundland controls (OR = 1.26(0.99-1.59); p < 0.05)), whereas the frequency of two (2) copies of the UGT2B17 gene CNV was 0.40 in the Alberta AS cases and 0.39 in the Alberta controls (OR = 1.05(95% CI: 0.83-1.33); p < 0.71)). Conclusions A genome-wide microarray interrogation of a large multiplex AS family revealed segregation of the UGT2B17 gene CNV among all affected family members. The association of the UGT2B17 CNV with AS is particularly interesting given the recent association of this CNV with osteoporosis and the proposed function as it encodes a key enzyme that inhibits androgens. However, two copies of the UGT2B17 gene CNV were only marginally significant in a uniplex AS cohort from Newfoundland but not in a uniplex AS cohort from Alberta. PMID:23927372

  16. Design and analysis report for the RL10-2B breadboard low thrust engine

    NASA Technical Reports Server (NTRS)

    Brown, J. R.; Foust, R. R.; Galler, D. E.; Kanic, P. G.; Kmiec, T. D.; Limerick, C. D.; Peckham, R. J.; Swartwout, T.

    1984-01-01

    The breadboard low thrust RL10-2B engine is described. A summary of the analysis and design effort to define the multimode thrust concept applicable to the requirements for the upper stage vehicles is provided. Baseline requirements were established for operation of the RL10-2B engine under the following conditions: (1) tank head idle at low propellant tank pressures without vehicle propellant conditioning or settling thrust; (2) pumped idle at a ten percent thrust level for low G deployment and/or vehicle tank pressurization; and (3) full thrust (15,000 lb.). Several variations of the engine configuration were investigated and results of the analyses are included.

  17. Germline duplication of ATG2B and GSKIP predisposes to familial myeloid malignancies.

    PubMed

    Saliba, Joseph; Saint-Martin, Cécile; Di Stefano, Antonio; Lenglet, Gaëlle; Marty, Caroline; Keren, Boris; Pasquier, Florence; Valle, Véronique Della; Secardin, Lise; Leroy, Gwendoline; Mahfoudhi, Emna; Grosjean, Sarah; Droin, Nathalie; Diop, M'boyba; Dessen, Philippe; Charrier, Sabine; Palazzo, Alberta; Merlevede, Jane; Meniane, Jean-Côme; Delaunay-Darivon, Christine; Fuseau, Pascal; Isnard, Françoise; Casadevall, Nicole; Solary, Eric; Debili, Najet; Bernard, Olivier A; Raslova, Hana; Najman, Albert; Vainchenker, William; Bellanné-Chantelot, Christine; Plo, Isabelle

    2015-10-01

    No major predisposition gene for familial myeloproliferative neoplasms (MPN) has been identified. Here we demonstrate that the autosomal dominant transmission of a 700-kb duplication in four genetically related families predisposes to myeloid malignancies, including MPN, frequently progressing to leukemia. Using induced pluripotent stem cells and primary cells, we demonstrate that overexpression of ATG2B and GSKIP enhances hematopoietic progenitor differentiation, including of megakaryocytes, by increasing progenitor sensitivity to thrombopoietin (TPO). ATG2B and GSKIP cooperate with acquired JAK2, MPL and CALR mutations during MPN development. Thus, the germline duplication may change the fitness of cells harboring signaling pathway mutations and increases the probability of disease development. PMID:26280900

  18. Microwave-assisted synthesis and electrochemical evaluation of VO2 (B) nanostructures

    SciTech Connect

    Ashton, Thomas E.; Borras, David Hevia; Iadecola, Antonella; Wiaderek, Kamila Magdalena; Chapman, Karena W.; Corr, Serena A.

    2015-12-01

    Abstract Understanding how intercalation materials change during electrochemical operation is paramount to optimising their behaviour and function and in situ characterisation methods allow us to observe these changes without sample destruction. Here, we first report the improved intercalation properties of bronze phase vanadium dioxide VO2 (B) prepared by a microwave assisted route which exhibits a larger electrochemical capacity (232 mAh g-1) compared to VO2 (B) prepared by a solvothermal route (197 mAh g-1). These electrochemical differences have also been followed using in situ X-ray absorption spectroscopy allowing us to follow oxidation state changes as they occur during battery operation.

  19. Adora2b Signaling on Bone Marrow Derived Cells Dampens Myocardial Ischemia-Reperfusion Injury

    PubMed Central

    Koeppen, Michael; Harter, Patrick N.; Bonney, Stephanie; Bonney, Megan; Reithel, Susan; Zachskorn, Cornelia; Mittelbronn, Michel; Eckle, Tobias

    2012-01-01

    Background Cardiac ischemia-reperfusion injury (I/R) represents a major cause of cardiac tissue injury. Adenosine signaling dampens inflammation during cardiac I/R. Here, we investigated the role of the adenosine A2b-receptor (Adora2b) on inflammatory cells during cardiac I/R. Methods To study Adora2b signaling on inflammatory cells, we transplanted wild-type (WT) bone marrow (BM) into Adora2b−/− mice or Adora2b−/− BM into WT mice. To study the role of polymorphonuclear leukocytes (PMNs), neutrophil-depleted WT mice were treated with an Adora2b agonist. Following treatments, mice were exposed to 60 min of myocardial ischemia and 120 min of reperfusion. Infarct sizes and Troponin-I levels were determined by triphenyltetrazolium chloride staining and ELISA, respectively. Results Transplantation of WT-BM into Adora2b−/− mice decreased infarct sizes by 19 ± 4% and Troponin-I by 87.5 ± 25.3 ng/ml (mean ± SD, n = 6). Transplantation of Adora2b−/− BM into WT mice increased infarct sizes by 20 ±3% and Troponin-I levels by 69.7 ± 17.9 ng/ml (mean ± SD, n = 6). Studies on the reperfused myocardium revealed PMNs as dominant cell type. PMN-depletion or Adora2b agonist treatment reduced infarct sizes by 30 ± 11% or 26 ± 13% (mean ± SD, n = 4), however the combination of both did not reveal further cardioprotection. Cytokine profiling showed significantly higher cardiac tumor-necrosis-factor-α levels in Adora2b−/− compared to WT mice (39.3 ± 5.3 vs. 7.5 ± 1.0 pg/mg protein, mean ± SD, n = 4). Pharmacological studies on human activated PMNs revealed an Adora2b dependent tumor-necrosis-factor-α release. Conclusion Adora2b signaling on BM-derived cells such as PMNs represents an endogenous cardioprotective mechanism during cardiac I/R. Our findings suggest that Adora2b agonist treatment during cardiac I/R reduces tumor-necrosis-factor-α release of PMNs, thereby dampening tissue injury. PMID:22531331

  20. Follow-up of patients with mycosis fungoides after interferon α2b treatment failure

    PubMed Central

    Studziński, Maciej; Giebel, Sebastian; Krause, Anna; Olejniczak, Monika; Grzanka, Aleksandra

    2015-01-01

    Introduction Treatment of T cell cutaneous lymphoma( CTCL) is a controversial subject and the effectiveness of treatment is still low. Aim Report of single center experience of management CTCL after progression after first line treatment. Material and methods We present 41 patients with CTCL, 29 received interferon α2b in first line, and 12 of them received second line therapy. Results Overall response rate for second line therapy was 60%. Conclusions Results of the follow-up of patients with mycosis fungoides after interferon α2b treatment failure with the literature review and discussion. PMID:26015774

  1. Competition of superconductivity and antiferromagnetism in RNi2B2C (R = Tm, Dy, Ho, Er)

    NASA Astrophysics Data System (ADS)

    Sahoo, B. K.; Panda, B. N.

    2015-06-01

    The co-existence of superconductivity (SC) and antiferromagnetism (AFM) in RNi2B2C (R = Tm, Dy, Ho, Er) is reported in this paper. A mean field Hamiltonian model is taken for the system. The order parameters corresponding to SC and AFM are determined and their variation with temperature are studied for these borocarbide superconductors. The interplay of SC and AFM shows BCS type of two gaps in the quasi-particle density of states. Our theoretical study is an attempt to reveal how far the s-wave pairing taken in our model could explain the coexistence properties of SC and AFM in RNi2B2C.

  2. Recent improvements in the development of A2B adenosine receptor agonists

    PubMed Central

    Tabrizi, Mojgan Aghazadeh; Fruttarolo, Francesca; Romagnoli, Romeo; Preti, Delia

    2009-01-01

    Adenosine is known to exert most of its physiological functions by acting as local modulator at four receptor subtypes named A1, A2A, A2B and A3 (ARs). Principally as a result of the difficulty in identifying potent and selective agonists, the A2B AR is the least extensively characterised of the adenosine receptors family. Despite these limitations, growing understanding of the physiological meaning of this target indicates promising therapeutic perspectives for specific ligands. As A2B AR signalling seems to be associated with pre/postconditioning cardioprotective and anti-inflammatory mechanisms, selective agonists may represent a new therapeutic group for patients suffering from coronary artery disease. Herein we present an overview of the recent advancements in identifying potent and selective A2B AR agonists reported in scientific and patent literature. These compounds can be classified into adenosine-like and nonadenosine ligands. Nucleoside-based agonists are the result of modifying adenosine by substitution at the N6-, C2-positions of the purine heterocycle and/or at the 5′-position of the ribose moiety or combinations of these substitutions. Compounds 1-deoxy-1-{6-[N′-(furan-2-carbonyl)-hydrazino]-9H-purin-9-yl}-N-ethyl-β-D-ribofuranuronamide (19, hA1Ki = 1050 nM, hA2AKi = 1550 nM, hA2B EC50 = 82 nM, hA3Ki > 5 μM) and its 2-chloro analogue 23 (hA1Ki = 3500 nM, hA2AKi = 4950 nM, hA2B EC50 = 210 nM, hA3Ki > 5 μM) were confirmed to be potent and selective full agonists in a cyclic adenosine monophosphate (cAMP) functional assay in Chinese hamster ovary (CHO) cells expressing hA2B AR. Nonribose ligands are represented by conveniently substituted dicarbonitrilepyridines, among which 2-[6-amino-3,5-dicyano-4-[4-(cyclopropylmethoxy)phenyl]pyridin-2-ylsulfanyl]acetamide (BAY-60–6583, hA1, hA2A, hA3 EC50 > 10 μM; hA2B EC50 = 3 nM) is currently under preclinical-phase investigation for treating coronary

  3. Recent improvements in the development of A2B adenosine receptor agonists

    PubMed Central

    Tabrizi, Mojgan Aghazadeh; Fruttarolo, Francesca; Romagnoli, Romeo; Preti, Delia

    2008-01-01

    Adenosine is known to exert most of its physiological functions by acting as local modulator at four receptor subtypes named A1, A2A, A2B and A3 (ARs). Principally as a result of the difficulty in identifying potent and selective agonists, the A2B AR is the least extensively characterised of the adenosine receptors family. Despite these limitations, growing understanding of the physiological meaning of this target indicates promising therapeutic perspectives for specific ligands. As A2B AR signalling seems to be associated with pre/postconditioning cardioprotective and anti-inflammatory mechanisms, selective agonists may represent a new therapeutic group for patients suffering from coronary artery disease. Herein we present an overview of the recent advancements in identifying potent and selective A2B AR agonists reported in scientific and patent literature. These compounds can be classified into adenosine-like and nonadenosine ligands. Nucleoside-based agonists are the result of modifying adenosine by substitution at the N6-, C2-positions of the purine heterocycle and/or at the 5′-position of the ribose moiety or combinations of these substitutions. Compounds 1-deoxy-1-{6-[N′-(furan-2-carbonyl)-hydrazino]-9H-purin-9-yl}-N-ethyl-β-D-ribofuranuronamide (19, hA1Ki = 1050 nM, hA2AKi = 1550 nM, hA2B EC50 = 82 nM, hA3Ki > 5 μM) and its 2-chloro analogue 23 (hA1Ki = 3500 nM, hA2AKi = 4950 nM, hA2B EC50 = 210 nM, hA3Ki > 5 μM) were confirmed to be potent and selective full agonists in a cyclic adenosine monophosphate (cAMP) functional assay in Chinese hamster ovary (CHO) cells expressing hA2B AR. Nonribose ligands are represented by conveniently substituted dicarbonitrilepyridines, among which 2-[6-amino-3,5-dicyano-4-[4-(cyclopropylmethoxy)phenyl]pyridin-2-ylsulfanyl]acetamide (BAY-60–6583, hA1, hA2A, hA3 EC50 > 10 μM; hA2B EC50 = 3 nM) is currently under preclinical-phase investigation for treating coronary

  4. Superconductivity and magnetism and their interplay in quaternary borocarbides RNi2B2C

    NASA Astrophysics Data System (ADS)

    Gupta, L. C.

    2006-12-01

    Since 1986, most of the interest in superconductivity became focused on high-Tc cuprates. The discovery of the superconducting quaternary borocarbide system Y Ni B C with Tc as high as ˜12 K inspired research into intermetallic superconductors (IMS) once again. Several reasons can be attributed to this revival of interest in IMS: (i) In the tetragonal quaternary magnetic superconductors RNi2B2C, superconductivity and magnetism occur with Tc and TN ˜ 10 K, thereby allowing studies of exotic phenomena associated with, and arising from, the interplay of superconductivity and magnetism. (ii) High TN's and a variety of commensurate and incommensurate magnetic structures in RNi2B2C (Fermi surface nesting playing a central role) strongly suggest that R-spins are coupled via the RKKY-exchange interaction. Hence, unlike in most other magnetic superconductors known so far, conduction electrons take part in superconductivity and magnetism. (iii) Quaternary borocarbides open up new pathways to try and synthesize multicomponent intermetallic superconductors. Their remarkable intrinsic superconducting and magnetic properties and the availability of high quality samples (bulk polycrystalline, large single crystals and thin films) make RNi2B2C particularly special to investigate. Several unusual phenomena have been reported, such as, to name a few, dramatic phonon mode softening at Tc, Hc2(T) exhibiting a positive curvature near Tc and a four-fold anisotropy in the basal plane; a variety of exceptional and fascinating flux line lattice (FLL) related effects — FLL-symmetry transformations and alignments with the underlying crystal lattice as a function of applied field (manifestation of nonlocal electrodynamics despite high κ ˜ 10, and thermal fluctuation effects even though Tc, ˜ 16 K, is not too high) and a four-fold symmetric star-shaped (in real space) vortex core. RNi2B2C are strong coupling s-wave BCS superconductors and, remarkably, have a

  5. CYP2B6*6 and CYP2B6*18 Predict Long-Term Efavirenz Exposure Measured in Hair Samples in HIV-Positive South African Women.

    PubMed

    Röhrich, Carola R; Drögemöller, Britt I; Ikediobi, Ogechi; van der Merwe, Lize; Grobbelaar, Nelis; Wright, Galen E B; McGregor, Nathaniel; Warnich, Louise

    2016-06-01

    Long-term exposure to efavirenz (EFV) measured in hair samples may predict response to antiretroviral treatment (ART). Polymorphisms in CYP2B6 are known to alter EFV levels. The aim of this study was to assess the relationship between CYP2B6 genotype, EFV levels measured in hair, and virological outcomes on ART in a real-world setting. We measured EFV levels in hair from HIV-positive South African females who had been receiving EFV-based treatment for at least 3 months from the South African Black (SAB) (n = 81) and Cape Mixed Ancestry (CMA) (n = 53) populations. Common genetic variation in CYP2B6 was determined in 15 individuals from each population using bidirectional Sanger sequencing. Prioritized variants (n = 16) were subsequently genotyped in the entire patient cohort (n = 134). The predictive value of EFV levels in hair and selected variants in CYP2B6 on virological treatment outcomes was assessed. Previously described alleles (CYP2B6*2, CYP2B6*5, CYP2B6*6, CYP2B6*17, and CYP2B6*18), as well as two novel alleles (CYP2B6*31 and CYP2B6*32), were detected in this study. Compared to noncarriers, individuals homozygous for CYP2B6*6 had ∼109% increased EFV levels in hair (p = .016) and CYP2B6*18 heterozygotes demonstrated 82% higher EFV hair levels (p = .0006). This study confirmed that alleles affecting CYP2B6 metabolism and subsequent EFV exposure are present at significant frequencies in both the SAB and CMA populations. Furthermore, this study demonstrated that the use of hair samples for testing EFV concentrations may be a useful tool in determining long-term drug exposure in resource-limited countries. PMID:26655325

  6. Pharmacogenetics of CYP2B6, CYP2A6 and UGT2B7 in HIV treatment in African populations: focus on efavirenz and nevirapine.

    PubMed

    Čolić, Antoinette; Alessandrini, Marco; Pepper, Michael S

    2015-05-01

    The CYP450 and UGT enzymes are involved in phase I and phase II metabolism of the majority of clinically prescribed drugs, including the non-nucleoside reverse transcriptase inhibitors, efavirenz and nevirapine, used in the treatment of HIV/AIDS. Variations in the activity of these enzymes due to gene polymorphisms can affect an individual's drug response or may lead to adverse drug reactions. There is an inter-ethnic distribution in the frequency of these polymorphisms, with African populations exhibiting higher genetic diversity compared to other populations. African specific alleles with clinical relevance have also emerged. Given the high prevalence of HIV/AIDS in sub-Saharan Africa, understanding the frequency of pharmacogenetically relevant alleles in populations of African origin, and their impact on efavirenz and nevirapine metabolism, is becoming increasingly critical. This review aims to investigate ethnic variation of CYP2B6, CYP2A6 and UGT2B7, and to understand the pharmacogenetic relevance when comparing frequencies in African populations to other populations worldwide. PMID:25391641

  7. Li4Ge2B as a new derivative of the Mo2B5 and Li5Sn2 structure types.

    PubMed

    Pavlyuk, Volodymyr; Ciesielski, Wojciech; Rozdzynska-Kielbik, Beata; Dmytriv, Grygoriy; Ehrenberg, Helmut

    2016-07-01

    Binary and multicomponent intermetallic compounds based on lithium and p-elements of Groups III-V of the Periodic Table are useful as modern electrode materials in lithium-ion batteries. However, the interactions between the components in the Li-Ge-B ternary system have not been reported. The structure of tetralithium digermanium boride, Li4Ge2B, exhibits a new structure type, in the noncentrosymmetric space group R3m, in which all the Li, Ge and B atoms occupy sites with 3m symmetry. The title structure is closely related to the Mo2B5 and Li5Sn2 structure types, which crystallize in the centrosymmetric space group R-3m. All the atoms in the title structure are coordinated by rhombic dodecahedra (coordination number = 14), similar to the atoms in related structures. According to electronic structure calculations using the tight-binding-linear muffin-tin orbital-atomic spheres approximation (TB-LMTO-ASA) method, strong covalent Ge-Ge and Ge-B interactions were established. PMID:27377278

  8. Identification of A2B5-positive putative oligodendrocyte progenitor cells and A2B5-positive astrocytes in adult human white matter.

    PubMed

    Scolding, N J; Rayner, P J; Compston, D A

    1999-03-01

    Spontaneous remyelination of previously demyelinated axons is found in a substantial minority of acute and chronic lesions in multiple sclerosis. In the rodent, central remyelination restores saltatory conduction and helps restore limb function, and it seems likely that endogenous myelin repair contributes to neurological recovery in multiple sclerosis. However, the identity of the remyelinating cell remains enigmatic. Fully differentiated oligodendrocytes have very limited capacity for recapitulating their developmental activities and re-engaging myelination pathways. Proliferative oligodendrocyte progenitors--often known as O-2A cells because of their ability to differentiate in vitro into either oligodendrocytes or ("type 2") astrocytes--are, in contrast, extremely efficient at myelin repair either spontaneously, or after transplantation into the de- or dysmyelinated CNS. Oligodendrocyte progenitors are present in both developing and adult rodent CNS. We have previously demonstrated that proliferative oligodendrocyte progenitors are present in cultures prepared from the adult human CNS. Here, using fresh tissue print preparations, we report that cells with processes and the A2B5-positive immunophenotype of proliferative oligodendrocyte progenitors are present in situ in adult human white matter. This technique also reveals the occurrence of A2B5-positive astrocytes, a cell also not previously identified in the normal adult human CNS. In the light of the rodent data showing the importance of oligodendrocyte progenitors in myelin repair, our findings suggesting the presence of progenitors in the adult human brain may have significant implications for spontaneous remyelination in multiple sclerosis and other demyelinating conditions. PMID:10051212

  9. Serotonin Receptor 2B Mediates Mechanical Hyperalgesia by Regulating Transient Receptor Potential Vanilloid 1.

    PubMed

    Su, Yeu-Shiuan; Chiu, Yuan-Yi; Lin, Shih-Yuan; Chen, Chih-Cheng; Sun, Wei-Hsin

    2016-05-01

    Serotonin [5-hydroxytryptamine (5-HT)], an inflammatory mediator, contributes to inflammatory pain. The presence of multiple 5-HT subtype receptors on peripheral and central nociceptors complicates the role of 5-HT in pain. Previously, we found that 5-HT2B/2C antagonist could block 5-HT-induced mechanical hyperalgesia. However, the types of neurons or circuits underlying this effect remained unsolved. Here, we demonstrate that the Gq/11-phospholipase Cβ-protein kinase Cε (PKCε) pathway mediated by 5-HT2B is involved in 5-HT-induced mechanical hyperalgesia in mice. Administration of a transient receptor potential vanilloid 1 (TRPV1) antagonist inhibited the 5-HT-induced mechanical hyperalgesia. 5-HT injection enhanced 5-HT- and capsaicin-evoked calcium signals specifically in isolectin B4 (IB4)-negative neurons; signals were inhibited by a 5-HT2B/2C antagonist and PKCε blocker. Thus, 5-HT2B mediates 5-HT-induced mechanical hyperalgesia by regulating TRPV1 function. PMID:26635025

  10. Combustion of Na 2B 4O 7 + Mg + C to synthesis B 4C powders

    NASA Astrophysics Data System (ADS)

    Guojian, Jiang; Jiayue, Xu; Hanrui, Zhuang; Wenlan, Li

    2009-09-01

    Boron carbide powder was fabricated by combustion synthesis (CS) method directly from mixed powders of borax (Na 2B 4O 7), magnesium (Mg) and carbon. The adiabatic temperature of the combustion reaction of Na 2B 4O 7 + 6 Mg + C was calculated. The control of the reactions was achieved by selecting reactant composition, relative density of powder compact and gas pressure in CS reactor. The effects of these different influential factors on the composition and morphologies of combustion products were investigated. The results show that, it is advantageous for more Mg/Na 2B 4O 7 than stoichiometric ratio in Na 2B 4O 7 + Mg + C system and high atmosphere pressure in the CS reactor to increase the conversion degree of reactants to end product. The final product with the minimal impurities' content could be fabricated at appropriate relative density of powder compact. At last, boron carbide without impurities could be obtained after the acid enrichment and distilled water washing.

  11. 76 FR 21036 - Application of the Prevailing Wage Methodology in the H-2B Program

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-14

    .... \\1\\ Wage Methodology for the Temporary Non-agricultural Employment H-2B Program, 76 FR 3452, Jan. 19... Program, 75 FR 61578, Oct. 5, 2010. The NPRM proposed to revise the methodology by which prevailing wages... work performed on or after January 1, 2012.'' 76 FR 3452, 3462, Jan. 19, 2011. The Department...

  12. Discovery of novel potent imidazo[1,2-b]pyridazine PDE10a inhibitors.

    PubMed

    Meegalla, Sanath K; Huang, Hui; Illig, Carl R; Parks, Daniel J; Chen, Jinsheng; Lee, Yu-Kai; Wilson, Kenneth J; Patel, Sharmila K; Cheung, Wing S; Lu, Tianbao; Kirchner, Thomas; Askari, Hossein B; Geisler, John; Patch, Raymond J; Gibbs, Alan C; Rady, Brian; Connelly, Margery; Player, Mark R

    2016-09-01

    Design and optimization of a novel series of imidazo[1,2-b]pyridazine PDE10a inhibitors are described. Compound 31 displays excellent pharmacokinetic properties and was also evaluated as an insulin secretagogue in vitro and in vivo. PMID:27491708

  13. Lovastatin exerts protective effects on endothelial cells via upregulation of PTK2B

    PubMed Central

    Chu, Weiwei; Guan, Lili; Huang, Dihua; Ren, Yuezhong; Zhou, Yan

    2016-01-01

    Statins are HMG-CoA reductase inhibitors that are used to decrease the blood levels of low-density lipoprotein (LDL). In addition, they have been shown to exert pleiotropic protective effects in the absence of LDL-lowering activity. The present study investigated the effects of lovastatin on global gene expression in human umbilical vein endothelial cells (HUVECs), in order to further explore its ability to protect against oxidized (ox)-LDL-induced cytotoxicity. HUVECs were treated with lovastatin for 2–24 h, and gene expression patterns were analyzed using cDNA microarrays. The results suggested that numerous genes were regulated by lovastatin, including certain genes associated with cell survival, such as PTK2B, BCL2 and MAP3K3. In particular, PTK2B, which has been shown to exert anti-apoptotic effects against ox-LDL-induced cell injury, was upregulated by lovastatin. Knockdown of PTK2B was able to attenuate ox-LDL-induced cell injury, and this was associated with decreased levels of phosphorylated-AKT and eNOS, and inhibition of mitochondrial-dependent apoptosis. In conclusion, the results of the present study suggested that lovastatin protects against ox-LDL-induced cell injury, potentially via the upregulation of PTK2B, which regulates the anti-apoptosis signaling pathway. PMID:27602089

  14. Structure and Assembly of Group B Streptococcus Pilus 2b Backbone Protein

    PubMed Central

    Cozzi, Roberta; Malito, Enrico; Lazzarin, Maddalena; Nuccitelli, Annalisa; Castagnetti, Andrea; Bottomley, Matthew J.; Margarit, Immaculada; Maione, Domenico; Rinaudo, C. Daniela

    2015-01-01

    Group B Streptococcus (GBS) is a major cause of invasive disease in infants. Like other Gram-positive bacteria, GBS uses a sortase C-catalyzed transpeptidation mechanism to generate cell surface pili from backbone and ancillary pilin precursor substrates. The three pilus types identified in GBS contain structural subunits that are highly immunogenic and are promising candidates for the development of a broadly-protective vaccine. Here we report the X-ray crystal structure of the backbone protein of pilus 2b (BP-2b) at 1.06Å resolution. The structure reveals a classical IgG-like fold typical of the pilin subunits of other Gram-positive bacteria. The crystallized portion of the protein (residues 185-468) encompasses domains D2 and D3 that together confer high stability to the protein due to the presence of an internal isopeptide bond within each domain. The D2+D3 region, lacking the N-terminal D1 domain, was as potent as the entire protein in conferring protection against GBS challenge in a well-established mouse model. By site-directed mutagenesis and complementation studies in GBS knock-out strains we identified the residues and motives essential for assembly of the BP-2b monomers into high-molecular weight complexes, thus providing new insights into pilus 2b polymerization. PMID:25942637

  15. Histone H2B mutations in inner region affect ubiquitination, centromere function, silencing and chromosome segregation.

    PubMed

    Maruyama, Takeshi; Nakamura, Takahiro; Hayashi, Takeshi; Yanagida, Mitsuhiro

    2006-06-01

    The reiterated nature of histone genes has hampered genetic approach to dissect the role of histones in chromatin dynamics. We here report isolation of three temperature-sensitive (ts) Schizosaccharomyces pombe strains, containing amino-acid substitutions in the sole histone H2B gene (htb1+). The mutation sites reside in the highly conserved, non-helical residues of H2B, which are implicated in DNA-protein or protein-protein interactions in the nucleosome. In the allele of htb1-72, the substitution (G52D) occurs at the DNA binding loop L1, causing disruption of the gene silencing in heterochromatic regions and lagging chromosomes in anaphase. In another allele htb1-223 (P102L) locating in the junction between alpha3 and alphaC, the mutant residue is in contact with H2A and other histones, leading to structural aberrations in the central centromere chromatin and unequal chromosome segregation in anaphase. The third allele htb1-442 (E34K) near alpha1 displayed little defect. Evidence is provided that monoubiquitinated H2B is greatly unstable in P102L mutant, possibly owing to proteasome-independent destruction or enhanced deubiquitination. Histone H2B thus plays an important role in centromere/kinetochore formation. PMID:16688222

  16. New benzoyl urea derivatives as novel NR2B selective NMDA receptor antagonists.

    PubMed

    Borza, I; Greiner, I; Kolok, S; Galgóczy, K; Ignácz-Szendrei, Gy; Horváth, Cs; Farkas, S; Gáti, T; Háda, V; Domány, Gy

    2006-09-01

    A novel series of benzoyl urea derivatives was prepared and identified as NR2B selective NMDA receptor antagonists. The influence of the substitution of the piperidine ring on the biological activity of the compounds was studied. Compound 9 was active in the formalin test in mice. PMID:17020160

  17. Copy number variations in the amylase gene (AMY2B) in Japanese native dog breeds.

    PubMed

    Tonoike, A; Hori, Y; Inoue-Murayama, M; Konno, A; Fujita, K; Miyado, M; Fukami, M; Nagasawa, M; Mogi, K; Kikusui, T

    2015-10-01

    A recent study suggested that increased copy numbers of the AMY2B gene might be a crucial genetic change that occurred during the domestication of dogs. To investigate AMY2B expansion in ancient breeds, which are highly divergent from modern breeds of presumed European origins, we analysed copy numbers in native Japanese dog breeds. Copy numbers in the Akita and Shiba, two ancient breeds in Japan, were higher than those in wolves. However, compared to a group of various modern breeds, Akitas had fewer copy numbers, whereas Shibas exhibited the same level of expansion as modern breeds. Interestingly, average AMY2B copy numbers in the Jomon-Shiba, a unique line of the Shiba that has been bred to maintain their appearance resembling ancestors of native Japanese dogs and that originated in the same region as the Akita, were lower than those in the Shiba. These differences may have arisen from the earlier introduction of rice farming to the region in which the Shiba originated compared to the region in which the Akita and the Jomon-Shiba originated. Thus, our data provide insights into the relationship between the introduction of agriculture and AMY2B expansion in dogs. PMID:26358734

  18. 76 FR 3451 - Wage Methodology for the Temporary Non-agricultural Employment H-2B Program

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-01-19

    ... revised its regulation governing the permanent program. 69 FR 77326, Dec. 27, 2004. These revisions... govern the H-2B temporary worker program. 73 FR 78020, Dec. 19, 2008 (the 2008 Final Rule). The 2008... NPRM in accordance with the court's order, allowing a 30-day comment period. 75 FR 61578, Oct. 5,...

  19. Evaluation of the 2b-RAD method for genomic selection in scallop breeding.

    PubMed

    Dou, Jinzhuang; Li, Xue; Fu, Qiang; Jiao, Wenqian; Li, Yangping; Li, Tianqi; Wang, Yangfan; Hu, Xiaoli; Wang, Shi; Bao, Zhenmin

    2016-01-01

    The recently developed 2b-restriction site-associated DNA (2b-RAD) sequencing method provides a cost-effective and flexible genotyping platform for aquaculture species lacking sufficient genomic resources. Here, we evaluated the performance of this method in the genomic selection (GS) of Yesso scallop (Patinopecten yessoensis) through simulation and real data analyses using six statistical models. Our simulation analysis revealed that the prediction accuracies obtained using the 2b-RAD markers were slightly lower than those obtained using all polymorphic loci in the genome. Furthermore, a small subset of markers obtained from a reduced tag representation (RTR) library presented comparable performance to that obtained using all markers, making RTR be an attractive approach for GS purpose. Six GS models exhibited variable performance in prediction accuracy depending on the scenarios (e.g., heritability, sample size, population structure), but Bayes-alphabet and BLUP-based models generally outperformed other models. Finally, we performed the evaluation using an empirical dataset composed of 349 Yesso scallops that were derived from five families. The prediction accuracy for this empirical dataset could reach 0.4 based on optimal GS models. In summary, the genotyping flexibility and cost-effectiveness make 2b-RAD be an ideal genotyping platform for genomic selection in aquaculture breeding programs. PMID:26754638

  20. Long life hearth in blast furnace -- Kokura No. 2 B.F. of Sumitomo Metals

    SciTech Connect

    Yamamoto, Takaiku; Sunahara, Kouhei; Inada, Takanobu; Takatani, Kouji; Miyahara, Mitsuo; Sato, Yasusi; Hatano, Yasuhiko; Takata, Kouzo

    1997-12-31

    The factors elongating hearth life of Sumitomo Kokura No. 2 B.F. were investigated by use of an estimation system of the furnace hearth condition, which consisted of four mathematical simulation models. Lowered heat load operation together with integrated design of both refractories and cooling enabled the furnace life to be extended for over 16 years without severe damage in the hearth.

  1. The Atmospheric Circulation of the Eccentric Hot-Jupiter HAT-P-2b

    NASA Astrophysics Data System (ADS)

    Lewis, Nikole; Showman, A. P.; Fortney, J. J.; Knutson, H.; Marley, M. S.

    2013-06-01

    The hot-Jupiter HAT-P-2b has become a prime target for Spitzer Space Telescope observations aimed at understanding the atmospheric response of exoplanets on highly eccentric orbits. Here we present a suite of three-dimensional atmospheric circulation models for HAT-P-2b that investigates the effects of assumed atmospheric composition and rotation rate on global scale winds and thermal patterns. We compare and contrast atmospheric models for HAT-P-2b which assume one and five times solar metallicity, both with and without TiO/VO as atmospheric constituents, along with models which assume a rotation period half and twice the nominal pseudo-synchronous rotation period. We find that changes in assumed atmospheric metallicity and rotation rate do not significantly affect model predictions of the planetary flux as a function of orbital phase. However, models in which TiO/VO are present in the atmosphere develop a transient temperature inversion between the transit and secondary eclipse events that results in significant variations in the timing and magnitude of the peak of the planetary flux compared with models in which TiO/VO are omitted from the opacity tables. We find that no one single atmospheric model can reproduce the recently observed full and partial orbit phase curves at 3.6, 4.5 and 8.0 microns, which is likely due to non-equilibrium chemical processes not captured by our current atmospheric models for HAT-P-2b.

  2. Structure-activity relationships for in vitro diuretic activity of CAP2b in the housefly

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A series of truncated and Ala-replacement analogs of the peptide Manse-CAP2b (pELYAFPRV-NH2) were assayed for diuretic activity on Malpighian tubules of the housefly Musca domestica. The C-terminal hexapeptide proved to be the active core, the minimum sequence required to retain significant diureti...

  3. Complete Genome Sequence of Lelliottia Podophage phD2B

    PubMed Central

    Nowicki, Grzegorz; Kujawa, Natalia; Goździcka-Józefiak, Anna

    2014-01-01

    The genus Lelliottia was recently created from the group of environmental gammaproteobacteria previously included in the genus Enterobacter. Here, we report the complete genome sequence of phD2B, the first (according to our current knowledge) known phage that infects bacterium from the taxon. PMID:25428962

  4. Molecular characterization of the spliceosomal proteins U1A and U2B" from higher plants.

    PubMed Central

    Simpson, G G; Clark, G P; Rothnie, H M; Boelens, W; van Venrooij, W; Brown, J W

    1995-01-01

    In addition to their role in pre-mRNA splicing, the human spliceosomal proteins U1A and U2B" are important models of how RNP motif-containing proteins execute sequence-specific RNA binding. Genes encoding U1A and U2B" have been isolated from potato and thereby provide the only evolutionary comparison available for both proteins and represent the only full-length genes encoding plant spliceosomal proteins to have been cloned and characterized. In vitro RNA binding experiments revealed the ability of potato U2B" to interact with human U2A' to enhance sequence-specific binding and to distinguish cognate RNAs of either plant or animal origin. A comparison of the sequence of U1A and U2B" proteins indicated that multiple residues which could affect RNP motif conformation probably govern the specific distinction in RNA binding by these proteins. Since human U1A modulates polyadenylation in vertebrates, the possibility that plant U1A might be exploited in the characterization of this process in plants was examined. However, unlike vertebrate U1A, neither U1A from potato nor Arabidopsis bound their own mRNA and no evidence for binding to upstream efficiency elements in polyadenylation signals was obtained, suggesting that plant U1A is not involved in polyadenylation. Images PMID:7556097

  5. Using the Internet for B2B Activities: A Review and Future Directions for Research.

    ERIC Educational Resources Information Center

    Gattiker, Urs E.; Perlusz, Stefano; Bohmann, Kristoffer

    2000-01-01

    Illustrates some of the challenges that electronic commerce practitioners and researchers face, focusing on business to business (B2B) transactions. Highlights include a conceptual framework of Web user behavior; purchasing context; socio-demographic characteristics; cultural factors; economic factors; attitudes toward information technology;…

  6. Measurements of the Urbach tail for A2B6 mixed crystals by the photothermal method

    NASA Astrophysics Data System (ADS)

    Zakrzewski, J.; Malinski, M.; Strzałkowski, K.; Firszt, F.; Łęgowski, S.; Męczyńska, H.

    2010-03-01

    This paper presents the influence of the composition of several mixed A2B6 crystals on the broadening of the optical absorption coefficient spectra. This broadening is observed as the change of the piezoelectric spectra associated with the change oft he Urbach tail. This effect is interpreted as a result of the increase of the compositional disorder of the crystal lattice.

  7. Metformin inhibits histone H2B monoubiquitination and downstream gene transcription in human breast cancer cells.

    PubMed

    DU, Yu; Zheng, Haiyan; Wang, Jiang; Ren, Ye; Li, Mi; Gong, Chen; Xu, Fei; Yang, Caihong

    2014-08-01

    Metformin, one of the most widely prescribed antihyperglycemic drugs, has recently received increasing attention for its potential effects with regard to cancer prevention and treatment. However, the mechanisms behind the suppression of cancer cell growth by metformin remain far from completely understood. The aim of the present study was to investigate whether metformin could regulate histone modification and its downstream gene transcription, and its potential function in inhibiting breast cancer cell proliferation. A T47D cell proliferation curve was determined by cell counting following metformin treatment with differing doses or time courses. The cell cycle was analyzed by flow cytometry with propidium iodide staining. Histone H2B monoubiquitination was evaluated by western blotting subsequent to histone extraction. The histone H2B monoubiquitination downstream gene expression level was determined by quantitative PCR. The results showed that metformin changed the cell-cycle check-point and inhibited breast cancer cell proliferation in a dose-dependent manner. AMPK was activated and histone H2B monoubiquitination and downstream gene transcription were inhibited following metformin treatment in the T47D cells. The effect of metformin on T47D cell proliferation was dependent on AMPK activity. It was concluded that metformin can suppress breast cancer cell growth by the activation of AMPK and the inhibition of histone H2B monoubiquitination and downstream gene transcription. This study reveals a novel potential mechanism of cancer cell growth suppression by metformin. PMID:25009658

  8. Elementary Career Education Guide, Volume 2B: Career Awareness--Intermediate.

    ERIC Educational Resources Information Center

    Watertown Independent School District 1, SD.

    Volume 2B of the six-volume articulated elementary education career guide deals with the career awareness level of career education and aims at developing student career identity. The lessons in the volume are divided and color-coded by intermediate grade levels 1-3 corresponding respectively with grades 4-6 and are categorized by subject area and…

  9. IN VITRO GLUCURONIDATION OF APREPITANT: A MODERATE INHIBITOR OF UGT2B7

    PubMed Central

    House, Larry; Ramirez, Jacqueline; Seminerio, Michael; Mirkov, Snezana; Ratain, Mark J.

    2016-01-01

    Aprepitant, an oral antiemetic, commonly used in the prevention of chemotherapy-induced nausea and vomiting, is primarily metabolized by CYP3A4. Aprepitant glucuronidation has yet to be evaluated in humans. The contribution of human UDP-glucuronosyltransferase (UGT) isoforms to the metabolism of aprepitant was investigated by performing kinetic studies, inhibition studies, and correlation analyses. In addition, aprepitant was evaluated as an inhibitor of UGTs.Glucuronidation of aprepitant was catalyzed by UGT1A4 (82%), UGT1A3 (12%), and UGT1A8 (6%) and Kms were 161.6 ± 15.6 µM, 69.4 ± 1.9 µM, and 197.1 ± 28.2 µM, respectively. Aprepitant glucuronidation was significantly correlated with both UGT1A4 substrates anastrazole and imipramine (rs = 0.77, P < 0.0001 for both substrates; n = 44), and with the UGT1A3 substrate thyroxine (rs = 0.58, P < 0.0001; n = 44).We found aprepitant to be a moderate inhibitor of UGT2B7 with a Ki of ~10 µM for 4-MU, morphine, and zidovudine. Our results suggest aprepitant can alter clearance of drugs primarily eliminated by UGT2B7. Given the likelihood for first-pass metabolism by intestinal UGT2B7, this is of particular concern for oral aprepitant co-administered with oral substrates of UGT2B7, such as zidovudine and morphine. PMID:26053558

  10. Interaction of Mash1 and Phox2b in sympathetic neuron development.

    PubMed

    Stanke, Matthias; Stubbusch, Jutta; Rohrer, Hermann

    2004-03-01

    The transcription factors Mash1 and Phox2b are both essential for sympathetic neuron development. To understand in more detail their function and interaction, Phox2b and Mash1 were ectopically expressed in vivo, in peripheral nerve precursors. Here, we demonstrate that the Phox2b-induced generation of ectopic noradrenergic neurons in chick peripheral nerve involves the induction of Cash1, the chick homolog of Mash1. All Phox2-induced neurons coexpress the noradrenergic marker genes TH and DBH. Conversely, Mash1 induces neuronal differentiation characterized by the expression of generic neuronal genes SCG10, Hu and NF160; however, only a subpopulation of these neurons also displays an autonomic, noradrenergic phenotype. This context-dependent action of Mash1 implicates autonomic codeterminants, required for noradrenergic differentiation in response to Mash1. In contrast, Phox2b coordinates generic and noradrenergic gene expression, recruiting Mash1/Cash1, which may have a major function in the control of pan-neuronal gene expression during noradrenergic neuron development. PMID:15033166

  11. NREL Advanced Research Turbine (ART) Aerodynamic Design of ART-2B Rotor Blades

    SciTech Connect

    Griffin, D.A.

    2000-09-05

    The National Renewable Energy Laboratory (NREL) installed two Advanced Research Turbines (ART) at the National Wind Technology Center near Boulder, Colorado, to use as full-scale test beds for ongoing research efforts, including three-dimensional blade aerodynamics and the effects of various control methods on turbine loads and performance. The Westinghouse WWG-0600 was selected as a baseline configuration for the ART turbines. The first turbine, ART-1, is currently operational and has been used to collect a baseline set of performance and loads data. A second turbine, ART-2A, incorporates several major modifications and may be upgraded further to a configuration designated aRT-2B. Possible features of the ART-2B turbine include a multi-degree of freedom hum and newly designed rotor blades. Global energy concepts, L.L.C. provided engineering support to NREL in designing the components for the ART-2B turbine. This document provides a summary of work performed by GEC on the aerodynamic design of ART-2B rotor blades.

  12. Antigenicity of the Leishmania infantum histones H2B and H4 during canine viscerocutaneous leishmaniasis

    PubMed Central

    Soto, M; Requena, J M; Quijada, L; Perez, M J; Nieto, C G; Guzman, F; Patarroyo, M E; Alonso, C

    1999-01-01

    In this study we show that sera from dogs naturally infected with Leishmania infantum contain antibodies that specifically react against the parasite H2B and H4 histones. The Leishmania H2B and the amino-terminal region of the histone H4, expressed as fusion proteins, when confronted with sera from canine viscerocutaneous leishmaniasis (VCL) dogs, were recognized by 63% and 47%, respectively. No reactivity was detected when sera from dogs naturally infected with pathogens other than Leishmania were used. Using a collection of synthetic peptides covering the complete sequence of both proteins, we have determined that the main linear antigenic determinants are located in the amino-terminal domains of these histones. The humoral response against histones H2B and H4 induced during canine leishmaniasis was found to be specific for Leishmania histones, since no cross-reactivity of the VCL sera with mammal histones was observed. Also, a comparative study of the prevalence of antibodies among VCL sera against the four core histones of L. infantum was performed. Although a large heterogeneity of the humoral responses against these proteins was found, histones H2A and H3 seem to be more prevalent immunogens than histones H2B and H4 during canine natural leishmaniasis. The origin of the anti-histone humoral response and its possible implications in the pathogenesis of Leishmania infection are discussed. PMID:9933463

  13. Tbx2b is required for the development of the parapineal organ

    PubMed Central

    Snelson, Corey D.; Santhakumar, Kirankumar; Halpern, Marnie E.; Gamse, Joshua T.

    2010-01-01

    Structural differences between the left and right sides of the brain exist throughout the vertebrate lineage. By studying the zebrafish pineal complex, which exhibits notable asymmetries, both the genes and the cell movements that result in left-right differences can be characterized. The pineal complex consists of the midline pineal organ and the left-sided parapineal organ. The parapineal is responsible for instructing the asymmetric architecture of the bilateral habenulae, the brain nuclei that flank the pineal complex. Using in vivo time-lapse confocal microscopy, we find that the cells that form the parapineal organ migrate as a cluster of cells from the pineal complex anlage to the left side of the brain. In a screen for mutations that disrupted brain laterality, we identified a nonsense mutation in the T-box2b (tbx2b) gene, which encodes a transcription factor expressed in the pineal complex anlage. The tbx2b mutant makes fewer parapineal cells, and they remain as individuals near the midline rather than migrating leftward as a group. The reduced number and incorrect placement of parapineal cells result in symmetric development of the adjacent habenular nuclei. We conclude that tbx2b functions to specify the correct number of parapineal cells and to regulate their asymmetric migration. PMID:18385257

  14. Enantiomeric Propanolamines as selective N-Methyl-d-aspartate 2B Receptor Antagonists†

    PubMed Central

    Tahirovic, Yesim A.; Geballe, Matthew; Gruszecka-Kowalik, Ewa; Myers, Scott J.; Lyuboslavsky, Polina; Le, Phuong; French, Adam; Irier, Hasan; Choi, Woo-baeg; Easterling, Keith; Yuan, Hongjie; Wilson, Lawrence J.; Kotloski, Robert; McNamara, James O.; Dingledine, Raymond; Liotta, Dennis C.; Traynelis, Stephen F.; Snyder, James P.

    2011-01-01

    Enantiomeric propanolamines have been identified as a new class of NR2B-selective NMDA receptor antagonists. The most effective agents are biaryl structures, synthesized in six steps with overall yields ranging from 11–64%. The compounds are potent and selective inhibitors of NR2B-containing recombinant NMDA receptors with IC50 values between 30–100 nM. Potency is strongly controlled by substitution on both rings and the centrally located amine nitrogen. SAR analysis suggests that well-balanced polarity and chain-length factors provide the greatest inhibitory potency. Structural comparisons based on 3D shape analysis and electrostatic complementarity support this conclusion. The antagonists are neuroprotective in both in vitro and in vivo models of ischemic cell death. In addition, some compounds exhibit anticonvulsant properties. Unlike earlier generation NMDA receptor antagonists and some NR2B-selective antagonists, the present series of propanolamines does not cause increased locomotion in rodents. Thus, the NR2B-selective antagonists exhibit a range of therapeutically interesting properties. PMID:18800760

  15. Marine microbial biodiversity, bioinformatics and biotechnology (M2B3) data reporting and service standards

    PubMed Central

    2015-01-01

    Contextual data collected concurrently with molecular samples are critical to the use of metagenomics in the fields of marine biodiversity, bioinformatics and biotechnology. We present here Marine Microbial Biodiversity, Bioinformatics and Biotechnology (M2B3) standards for “Reporting” and “Serving” data. The M2B3 Reporting Standard (1) describes minimal mandatory and recommended contextual information for a marine microbial sample obtained in the epipelagic zone, (2) includes meaningful information for researchers in the oceanographic, biodiversity and molecular disciplines, and (3) can easily be adopted by any marine laboratory with minimum sampling resources. The M2B3 Service Standard defines a software interface through which these data can be discovered and explored in data repositories. The M2B3 Standards were developed by the European project Micro B3, funded under 7th Framework Programme “Ocean of Tomorrow”, and were first used with the Ocean Sampling Day initiative. We believe that these standards have value in broader marine science. PMID:26203332

  16. 75 FR 61577 - Wage Methodology for the Temporary Non-Agricultural Employment H-2B Program

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-10-05

    ... Department proposed and finalized regulations that currently govern the H-2B temporary worker program. 73 FR 29942, May 22, 2008; 73 FR 78020, Dec. 19, 2008 (the 2008 Final Rule). The 2008 Final Rule essentially... program. 75 FR 6884 (Feb. 12, 2010). \\1\\ Additionally, the decision issued by the court in Comit de...

  17. A Cross-Industry Review of B2B Critical Success Factors.

    ERIC Educational Resources Information Center

    Eid, Riyad; Trueman, Myfanwy; Ahmed, Abdel Moneim

    2002-01-01

    Presents a comprehensive review of B2B (business-to- business) international Internet marketing and identifies 21 critical success factors in five categories: marketing strategy, including management support, strategic goals, and collaboration; Web site factors, including Web site design; global factors, including multilanguage sites and cultural…

  18. 20 CFR 655.11 - Registration of H-2B employers.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... pending H-2B Registration. (j) Transition period. In order to allow OFLC to make the necessary changes to..., or an intermittent need, as defined at 8 CFR 214.2(h)(6)(ii)(B) and § 655.6 (or in the case of job... services or labor is temporary, regardless of whether the underlying job is permanent or temporary. 8...

  19. 20 CFR 655.11 - Registration of H-2B employers.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... pending H-2B Registration. (j) Transition period. In order to allow OFLC to make the necessary changes to..., or an intermittent need, as defined at 8 CFR 214.2(h)(6)(ii)(B) and § 655.6 (or in the case of job... services or labor is temporary, regardless of whether the underlying job is permanent or temporary. 8...

  20. Mutation screening of GRIN2B in schizophrenia and autism spectrum disorder in a Japanese population.

    PubMed

    Takasaki, Yuto; Koide, Takayoshi; Wang, Chenyao; Kimura, Hiroki; Xing, Jingrui; Kushima, Itaru; Ishizuka, Kanako; Mori, Daisuke; Sekiguchi, Mariko; Ikeda, Masashi; Aizawa, Miki; Tsurumaru, Naoko; Iwayama, Yoshimi; Yoshimi, Akira; Arioka, Yuko; Yoshida, Mami; Noma, Hiromi; Oya-Ito, Tomoko; Nakamura, Yukako; Kunimoto, Shohko; Aleksic, Branko; Uno, Yota; Okada, Takashi; Ujike, Hiroshi; Egawa, Jun; Kuwabara, Hitoshi; Someya, Toshiyuki; Yoshikawa, Takeo; Iwata, Nakao; Ozaki, Norio

    2016-01-01

    N-methyl-d-aspartate receptors (NMDARs) play a critical role in excitatory synaptic transmission and plasticity in the central nervous systems. Recent genetics studies in schizophrenia (SCZ) show that SCZ is susceptible to NMDARs and the NMDAR signaling complex. In autism spectrum disorder (ASD), several studies report dysregulation of NMDARs as a risk factor for ASD. To further examine the association between NMDARs and SCZ/ASD development, we conducted a mutation screening study of GRIN2B which encodes NR2B subunit of NMDARs, to identify rare mutations that potentially cause diseases, in SCZ and ASD patients (n = 574 and 152, respectively). This was followed by an association study in a large sample set of SCZ, ASD, and normal healthy controls (n = 4145, 381, and 4432, respectively). We identified five rare missense mutations through the mutation screening of GRIN2B. Although no statistically significant association between any single mutation and SCZ or ASD was found, one of its variant, K1292R, is found only in the patient group. To further examine the association between mutations in GRIN2B and SCZ/ASD development, a larger sample size and functional experiments are needed. PMID:27616045

  1. Magnetic structures in RNi{sub 2}B{sub 2}C (R = Ho, Er) superconductors

    SciTech Connect

    Stassis, C.; Goldman, A.I.; Dervenagas, P.; Zarestky, J.; Canfield, P.C.; Cho, B.K.; Johnston, D.C.; Sternlieb, B.; Sternlieb, B.

    1994-12-31

    Single crystal neutron diffraction techniques have been employed to study the evolution of magnetic structures in RNi{sub 2}B{sub 2}C compounds in an attempt to understand the relationship between magnetic ordering and superconductivity in several members of this series. For HoNi{sub 2}B{sub 2}C, below the superconducting transition (T{sub c} = 8 K), an incommensurate magnetic structure characterized by two wave vectors (0.585 a* and 0.915 c*) is found in a narrow temperature range between 4.7 K and 6 K. This is the same temperature range where bulk measurements find a deep minimum in the upper critical field, H{sub c2}. Below 4.7 K, HoNi{sub 2}B{sub 2}C is a simple collinear antiferromagnet. ErNi{sub 2}B{sub 2}C ({Tc} = 11 K) orders in an incommensurate modulated antiferromagnetic state characterized by an ordering wave vector 0.553 a* below 7 K, which coexists with superconductivity.

  2. Nonsuperconductivity and magnetic features of the intermetallic borocarbide HoCo2B2C

    NASA Astrophysics Data System (ADS)

    Rapp, R. E.; Massalami, M. El

    1999-08-01

    Intrigued by the exotic features of the low-temperature superconducting and magnetic phase diagram of HoNi2B2C, this work searched for similar features in the isomorphous HoCo2B2C [LuNi2B2C-type structure, a=3.500(3) Å, c=10.590(9) Å]. In contrast to the former, no superconductivity is observed down to 30 mK, indicative of a relative lattice stiffening and a reduction in N(EF). The magnetic ordering of the Ho sublattice sets in at TN=5.4(1) K (Co-sublattice carries no magnetic moment). The magnetic entropy up to 10 K is suggestive of an electronic ground-state doublet. No field-induced cascade of magnetic phase transitions was observed in the range 1.8 K2B2C and Ho metal. The T1 event, evident also in χac(T), is probably a manifestation of an order-to-order magnetic phase transition.

  3. Expression of adenosine A2b receptor in rat type II and III taste cells.

    PubMed

    Nishida, Kentaro; Dohi, Yukari; Yamanaka, Yuri; Miyata, Ai; Tsukamoto, Katsunobu; Yabu, Miharu; Ohishi, Akihiro; Nagasawa, Kazuki

    2014-05-01

    We previously demonstrated that equilibrative nucleoside transporter 1 was expressed in taste cells, suggesting the existence of an adenosine signaling system, but whether or not the expression of an adenosine receptor occurs in rat taste buds remains unknown. Therefore, we examined the expression profiles of adenosine receptors and evaluated their functionality in rat circumvallate papillae. Among adenosine receptors, the mRNA for an adenosine A2b receptor (A2bR) was expressed by the rat circumvallate papillae, and its expression level was significantly greater in the circumvallate papillae than in the non-taste lingual epithelium. A2bR-immunoreactivity was detected primarily in type II taste cells, and partial, but significant expression was also observed in type III ones, but there was no immunoreactivity in type I ones. The cAMP generation in isolated epithelium containing taste buds treated with 500 μM adenosine or 10 μM BAY60-6583 was significantly increased compared to in the controls. These findings suggest that adenosine plays a role in signaling transmission via A2bR between taste cells in rats. PMID:24327108

  4. The Atmospheric Circulation of Eccentric Hot Jupiter HAT-P-2b

    NASA Astrophysics Data System (ADS)

    Lewis, Nikole; Knutson, H.; Showman, A. P.; Fortney, J. J.; Agol, E.; Burrows, A.; Charbonneau, D.; Cowan, N. B.; Deming, D.; Desert, J.; Langton, J.; Laughlin, G.; Mighell, K.

    2011-09-01

    The Spitzer warm mission has already greatly expanded the field of exoplanet characterization with over 3000 hours of time dedicated to exoplanet observations. Observations of eclipsing systems with Spitzer are at the heart of these advances, as they allow us to move beyond simple mass and period estimates to determine planetary radius, dayside emission, and emission variations as a function of orbital phase. The eclipsing system HAT-P-2 is of special interest because the massive Jovian sized planet in this system is on a highly eccentric orbit (e=0.5171). Because HAT-P-2b's orbit is eccentric, the planet is subject to time variable heating and probable non-synchronous rotation. Circulation patterns that we expect to develop in HAT-P-2b's atmosphere will likely vary with both planetary local time and orbital phase. Here we present an analysis of two full-orbit light curves for the HAT-P-2 system obtained at 3.6 and 4.5 microns during the first two years of the Spitzer warm mission and discuss the observational constraints imposed on the atmospheric circulation of HAT-P-2b. Additionally, three-dimensional atmospheric models that incorporate realistic radiative transfer will be presented to further elucidate possible global scale circulations patterns present in the atmosphere of HAT-P-2b. Support for this work was provided by NASA.

  5. A Highly Conserved Region within H2B Is Important for FACT To Act on Nucleosomes

    PubMed Central

    Zheng, Suting; Crickard, J. Brooks; Srikanth, Abhinaya

    2014-01-01

    Histone N-terminal tails play crucial roles in chromatin-related processes. The tails of histones H3 and H4 are highly conserved and well characterized, but much less is known about the functions of the tails of histones H2A and H2B and their sequences are more divergent among eukaryotes. Here we characterized the function of the only highly conserved region in the H2B tail, the H2B repression (HBR) domain. Once thought to play a role only in repression, it also has an uncharacterized function in gene activation and DNA damage responses. We report that deletion of the HBR domain impairs the eviction of nucleosomes at the promoters and open reading frames of genes. A closer examination of the HBR domain mutants revealed that they displayed phenotypes similar to those of histone chaperone complex FACT mutants, including an increase in intragenic transcription and the accumulation of free histones in cells. Biochemical characterization of recombinant nucleosomes indicates that deletion of the HBR domain impairs FACT-dependent removal of H2A-H2B from nucleosomes, suggesting that the HBR domain plays an important role in allowing FACT to disrupt dimer-DNA interactions. We have uncovered a previously unappreciated role for the HBR domain in regulating chromatin structure and have provided insight into how FACT acts on nucleosomes. PMID:24248595

  6. Improved Serodiagnosis of Cystic Echinococcosis Using the New Recombinant 2B2t Antigen

    PubMed Central

    Hernández-González, Ana; Santivañez, Saúl; García, Héctor H.; Rodríguez, Silvia; Muñoz, Santiago; Ramos, Guillermo; Orduña, Antonio; Siles-Lucas, Mar

    2012-01-01

    A standardized test for the serodiagnosis of human cystic echinococcosis (CE) is still needed, because of the low specificity and sensitivity of the currently available commercial tools and the lack of proper evaluation of the existing recombinant antigens. In a previous work, we defined the new ELISA-B2t diagnostic tool for the detection of specific IgGs in CE patients, which showed high sensitivity and specificity, and was useful in monitoring the clinical evolution of surgically treated CE patients. Nevertheless, this recombinant antigen gave rise to false-negative results in a percentage of CE patients. Therefore, in an attempt to improve its sensitivity, we constructed B2t-derived recombinant antigens with two, four and eight tandem repeat of B2t units, and tested them by ELISA on serum samples of CE patients and patients with related parasites. The best diagnostic values were obtained with the two tandem repeat 2B2t antigen. The influence of several clinical variables on the performance of the tests was also evaluated. Finally, the diagnostic performance of the 2B2t-ELISA was compared with that of an indirect haemagglutination commercial test. The 2B2t recombinant antigen performed better than the HF and B2t antigens, and the IHA commercial kit. Therefore, this new 2B2t-ELISA is a promising candidate test for the serodiagnosis of CE in clinical settings. PMID:22802975

  7. 20 CFR 655.22 - Obligations of H-2B employers.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 20 Employees' Benefits 3 2011-04-01 2011-04-01 false Obligations of H-2B employers. 655.22 Section 655.22 Employees' Benefits EMPLOYMENT AND TRAINING ADMINISTRATION, DEPARTMENT OF LABOR TEMPORARY EMPLOYMENT OF FOREIGN WORKERS IN THE UNITED STATES Labor Certification Process and Enforcement of Attestations for Temporary Employment in...

  8. Endemic versus epidemic viral spreads display distinct patterns of HTLV-2b replication

    SciTech Connect

    Gabet, Anne-Sophie; Moules, Vincent; Sibon, David; Nass, Catharie C.; Mortreux, Franck; Mauclere, Philippe; Gessain, Antoine; Murphy, Edward L.; Wattel, Eric . E-mail: wattel@lyon.fnclcc.fr

    2006-02-05

    As the replication pattern of leukemogenic PTLVs possesses a strong pathogenic impact, we investigated HTLV-2 replication in vivo in asymptomatic carriers belonging into 2 distinct populations infected by the same HTLV-2b subtype. They include epidemically infected American blood donors, in whom HTLV-2b has been present for only 30 years, and endemically infected Bakola Pygmies from Cameroon, characterized by a long viral endemicity (at least few generations). In blood donors, both the circulating proviral loads and the degree of infected cell proliferation were largely lower than those characterizing asymptomatic carriers infected with leukemogenic PTLVs (HTLV-1, STLV-1). This might contribute to explain the lack of known link between HTLV-2b infection and the development of malignancies in this population. In contrast, endemically infected individuals displayed high proviral loads resulting from the extensive proliferation of infected cells. The route and/or the duration of infection, viral genetic drift, host immune response, genetic background, co-infections or a combination thereof might have contributed to these differences between endemically and epidemically infected subjects. As the clonality pattern observed in endemically infected individuals is very reminiscent of that of leukemogenic PTLVs at the pre-leukemic stage, our results highlight the possible oncogenic effect of HTLV-2b infection in such population.

  9. Identification of Lactobacillus UFV H2B20 (probiotic strain) using DNA-DNA hybridization

    PubMed Central

    de Magalhães, J.T.; Uetanabaro, A.P. T.; de Moraes, C.A.

    2008-01-01

    Sequence analyses of the 16S rDNA gene and DNA-DNA hybridization tests were performed for identification of the species of the probiotic Lactobacillus UFV H2b20 strain. Using these two tests, we concluded that this strain, originally considered Lact. acidophilus, should be classified as Lact. delbrueckii. PMID:24031263

  10. Mission and Sustainability of Informatics for Integrating Biology and the Bedside (i2b2)

    PubMed Central

    Murphy, Shawn; Wilcox, Adam

    2014-01-01

    Introduction: A visible example of a successfully disseminated research project in the healthcare space is Informatics for Integrating Biology and the Bedside, or i2b2. The project serves to provide the software that can allow a researcher to do direct, self-serve queries against the electronic healthcare data form a hospital. The goals of these queries are to find cohorts of patients that fit specific profiles, while providing for patient privacy and discretion. Sustaining this resource and keeping its direction has always been a challenge, but ever more so as the ten year National Centers for Biomedical Computing (NCBCs) sunset their funding. Findings: Building on the i2b2 structures has helped the dissemination plans for grants leveraging it because it is a disseminated national resource. While this has not directly increased the support of i2b2 internally, it has increased the ability of institutions to leverage the resource and generally leads to increased institutional support. Discussion: The successful development, use, and dissemination i2b2 has been significant in clinical research and informatics. Its evolution has been from a local research data infrastructure to one disseminated more broadly than any other product of the National Centers for Biomedical Computing, and an infrastructure spawning larger investments than were originally used to create it. Throughout this, there were two main lessons about the benefits of dissemination: that people have great creativity in utilizing a resource in different ways and that broader system use can make the system more robust. One option for long-term sustainability of the central authority would be to translate the function to an industry partner. Another option currently being pursued is to create a foundation that would be a central authority for the project. Conclusion: Over the past 10 years, i2b2 has risen to be an important staple in the toolkit of health care researchers. There are now over 110 hospitals

  11. Ferromagnetic ordering in CeIr2B2: Transport, magnetization, specific heat, and NMR studies

    NASA Astrophysics Data System (ADS)

    Prasad, A.; Anand, V. K.; Paramanik, U. B.; Hossain, Z.; Sarkar, R.; Oeschler, N.; Baenitz, M.; Geibel, C.

    2012-07-01

    We present a complete characterization of the ferromagnetic system CeIr2B2 using powder x-ray diffraction (XRD), magnetic susceptibility χ(T), isothermal magnetization M(H), specific heat C(T), electrical resistivity ρ(T,H), and thermoelectric power S(T) measurements. Furthermore, 11B NMR study was performed to probe the magnetism on a microscopic scale. Rietveld refinement of powder XRD data confirms that CeIr2B2 crystallizes in CaRh2B2-type orthorhombic structure (space group fddd). The χ(T), C(T), and ρ(T) data confirm bulk ferromagnetic ordering with Tc=5.1 K. Ce ions in CeIr2B2 are in a stable trivalent state. Our low-temperature C(T) data measured down to 0.4 K yield a Sommerfeld coefficient γ = 73(4) mJ/mol K2, which is much smaller than the previously reported value of γ = 180 mJ/mol K2 deduced from the specific heat measurement down to 2.5 K. For LaIr2B2, γ = 6(1) mJ/mol K2, which implies the density of states at the Fermi level D(EF)=2.54 states/(eV f.u.) for both spin directions. The renormalization factor for quasiparticle density of states and hence for quasiparticle mass due to 4f correlations in CeIr2B2 is ≈12. The Kondo temperature TK˜4 K is estimated from the jump in specific heat of CeIr2B2 at Tc. Both C(T) and ρ(T) data exhibit a gapped-magnon behavior in the magnetically ordered state with an energy gap Eg˜3.5 K. The ρ data as a function of magnetic field H indicate a large negative magnetoresistance (MR) which is highest for T=5 K. While at 5 K the negative MR keeps on increasing up to 10 T, at 2 K an upturn is observed near H=3.5 T. On the other hand, the thermoelectric power data have small absolute values (S˜7μV/K), indicating a weak Kondo interaction. A shoulder in S(T) at about 30 K, followed by a minimum at ˜10 K, is attributed to crystal electric field effects and the onset of magnetic ordering. 11B NMR line broadening provides strong evidence of ferromagnetic correlations below 40 K.

  12. Induction and inhibition of mouse cytochrome P-450 2B enzymes by musk xylene.

    PubMed

    Lehman-McKeeman, L D; Johnson, D R; Caudill, D

    1997-01-01

    Musk xylene (MX) (1,3,5-trinitro-2-t-butylxylene) is a nitromusk perfume ingredient that although uniformly negative in a battery of genotoxicity tests, produces a high incidence of liver tumors in mice. The purpose of this work was to characterize the profile and dose-response relationship of microsomal enzyme induction following exposure to MX. MX was dosed by gavage to male B6C3F1 mice for 7 days at 0, 1, 5, 10, 20, 50, 100, and 200 mg/kg after which microsomes were prepared. At 200 mg/kg, MX increased liver weight by about 65% and increased microsomal cytochrome P-450 content 2-fold over control. MX increased microsomal activity for O-dealkylation of 7-ethoxy and 7-methoxyresorufin 4- and 2-fold, respectively, and increased the N-demethylation of erythromycin approximately 2-fold. These results were generally consistent with increased CYP1A1, 1A2, and 3A protein levels determined by Western blotting. In contrast, whereas no increase in O-dealkylation of 7-pentoxyresorufin (PROD) was observed, MX treatment increased CYP2B protein levels about 25-fold over control at 200 mg/kg. Furthermore, a single dosage of MX (200 mg/kg) increased Cyp2b-10 mRNA to a maximal level and with a time course similar to phenobarbital (PB). To study inhibition of CYP2B enzymes in vivo, mice were treated with PB (0.05% in drinking water for 5 days), then given a single dosage of corn oil or MX (200 mg/kg) at 2 or 18 hr before necropsy. PB treatment increased PROD activity 25-fold, and at 2 hr after MX treatment (associated with peak plasma levels of MX), there was no change in the PB-induced PROD activity. However, at 18 hr, MX treatment decreased PROD activity by 90%. Despite the in vivo inhibition, in vitro studies indicated that MX did not cause mechanism-based inactivation of CYP2B enzymes. The potential for nitroreduction of MX (catalyzed by anaerobic intestinal bacteria) to contribute to the inhibition of CYP2B enzyme activity was evaluated in a separate group of PB-induced mice

  13. Equine cytochrome P450 2B6 — Genomic identification, expression and functional characterization with ketamine

    SciTech Connect

    Peters, L.M.; Demmel, S.; Pusch, G.; Buters, J.T.M.; Zielinski, J.; Leeb, T.; Mevissen, M.; Schmitz, A.

    2013-01-01

    Ketamine is an anesthetic and analgesic regularly used in veterinary patients. As ketamine is almost always administered in combination with other drugs, interactions between ketamine and other drugs bear the risk of either adverse effects or diminished efficacy. Since cytochrome P450 enzymes (CYPs) play a pivotal role in the phase I metabolism of the majority of all marketed drugs, drug–drug interactions often occur at the active site of these enzymes. CYPs have been thoroughly examined in humans and laboratory animals, but little is known about equine CYPs. The characterization of equine CYPs is essential for a better understanding of drug metabolism in horses. We report annotation, cloning and heterologous expression of the equine CYP2B6 in V79 Chinese hamster fibroblasts. After computational annotation of all CYP2B genes, the coding sequence (CDS) of equine CYP2B6 was amplified by RT-PCR from horse liver total RNA and revealed an amino acid sequence identity of 77% and a similarity of 93.7% to its human ortholog. A non-synonymous variant c.226G>A in exon 2 of the equine CYP2B6 was detected in 97 horses. The mutant A-allele showed an allele frequency of 82%. Two further variants in exon 3 were detected in one and two horses of this group, respectively. Transfected V79 cells were incubated with racemic ketamine and norketamine as probe substrates to determine metabolic activity. The recombinant equine CYP2B6 N-demethylated ketamine to norketamine and produced metabolites of norketamine, such as hydroxylated norketamines and 5,6-dehydronorketamine. V{sub max} for S-/and R-norketamine formation was 0.49 and 0.45 nmol/h/mg cellular protein and K{sub m} was 3.41 and 2.66 μM, respectively. The N-demethylation of S-/R-ketamine was inhibited concentration-dependently with clopidogrel showing an IC{sub 50} of 5.63 and 6.26 μM, respectively. The functional importance of the recorded genetic variants remains to be explored. Equine CYP2B6 was determined to be a CYP

  14. Adults with RRM2B-related mitochondrial disease have distinct clinical and molecular characteristics

    PubMed Central

    Pitceathly, Robert D. S.; Smith, Conrad; Fratter, Carl; Alston, Charlotte L.; He, Langping; Craig, Kate; Blakely, Emma L.; Evans, Julie C.; Taylor, John; Shabbir, Zarfishan; Deschauer, Marcus; Pohl, Ute; Roberts, Mark E.; Jackson, Matthew C.; Halfpenny, Christopher A.; Turnpenny, Peter D.; Lunt, Peter W.; Hanna, Michael G.; Schaefer, Andrew M.; McFarland, Robert; Horvath, Rita; Chinnery, Patrick F.; Turnbull, Douglass M.; Poulton, Joanna; Taylor, Robert W.

    2012-01-01

    Mutations in the nuclear-encoded mitochondrial maintenance gene RRM2B are an important cause of familial mitochondrial disease in both adults and children and represent the third most common cause of multiple mitochondrial DNA deletions in adults, following POLG [polymerase (DNA directed), gamma] and PEO1 (now called C10ORF2, encoding the Twinkle helicase) mutations. However, the clinico-pathological and molecular features of adults with RRM2B-related disease have not been clearly defined. In this multicentre study of 26 adult patients from 22 independent families, including five additional cases published in the literature, we show that extra-ocular neurological complications are common in adults with genetically confirmed RRM2B mutations. We also demonstrate a clear correlation between the clinical phenotype and the underlying genetic defect. Myopathy was a prominent manifestation, followed by bulbar dysfunction and fatigue. Sensorineural hearing loss and gastrointestinal disturbance were also important findings. Severe multisystem neurological disease was associated with recessively inherited compound heterozygous mutations with a mean age of disease onset at 7 years. Dominantly inherited heterozygous mutations were associated with a milder predominantly myopathic phenotype with a later mean age of disease onset at 46 years. Skeletal muscle biopsies revealed subsarcolemmal accumulation of mitochondria and/or cytochrome c oxidase-deficient fibres. Multiple mitochondrial DNA deletions were universally present in patients who underwent a muscle biopsy. We identified 18 different heterozygous RRM2B mutations within our cohort of patients, including five novel mutations that have not previously been reported. Despite marked clinical overlap between the mitochondrial maintenance genes, key clinical features such as bulbar dysfunction, hearing loss and gastrointestinal disturbance should help prioritize genetic testing towards RRM2B analysis, and sequencing of the gene

  15. GRIN2B Mutations in West Syndrome and Intellectual Disability with Focal Epilepsy

    PubMed Central

    Lemke, Johannes R; Hendrickx, Rik; Geider, Kirsten; Laube, Bodo; Schwake, Michael; Harvey, Robert J; James, Victoria M; Pepler, Alex; Steiner, Isabelle; Hörtnagel, Konstanze; Neidhardt, John; Ruf, Susanne; Wolff, Markus; Bartholdi, Deborah; Caraballo, Roberto; Platzer, Konrad; Suls, Arvid; De Jonghe, Peter; Biskup, Saskia; Weckhuysen, Sarah

    2014-01-01

    Objective To identify novel epilepsy genes using a panel approach and describe the functional consequences of mutations. Methods Using a panel approach, we screened 357 patients comprising a vast spectrum of epileptic disorders for defects in genes known to contribute to epilepsy and/or intellectual disability (ID). After detection of mutations in a novel epilepsy gene, we investigated functional effects in Xenopus laevis oocytes and screened a follow-up cohort. Results We revealed de novo mutations in GRIN2B encoding the NR2B subunit of the N-methyl-D-aspartate (NMDA) receptor in 2 individuals with West syndrome and severe developmental delay as well as 1 individual with ID and focal epilepsy. The patient with ID and focal epilepsy had a missense mutation in the extracellular glutamate-binding domain (p.Arg540His), whereas both West syndrome patients carried missense mutations within the NR2B ion channel-forming re-entrant loop (p.Asn615Ile, p.Val618Gly). Subsequent screening of 47 patients with unexplained infantile spasms did not reveal additional de novo mutations, but detected a carrier of a novel inherited GRIN2B splice site variant in close proximity (c.2011-5_2011-4delTC). Mutations p.Asn615Ile and p.Val618Gly cause a significantly reduced Mg2+ block and higher Ca2+ permeability, leading to a dramatically increased Ca2+ influx, whereas p.Arg540His caused less severe disturbance of channel function, corresponding to the milder patient phenotype. Interpretation We identified GRIN2B gain-of-function mutations as a cause of West syndrome with severe developmental delay as well as of ID with childhood onset focal epilepsy. Severely disturbed channel function corresponded to severe clinical phenotypes, underlining the important role of facilitated NMDA receptor signaling in epileptogenesis. PMID:24272827

  16. Dehydroepiandrosterone Induces Human CYP2B6 through the Constitutive Androstane Receptor

    PubMed Central

    Kőhalmy, Krisztina; Tamási, Viola; Kóbori, László; Sárváry, Enikő; Pascussi, Jean-Marc; Porrogi, Pálma; Rozman, Damjana; Prough, Russell A.; Meyer, Urs A.; Monostory, Katalin

    2008-01-01

    Dehydroepiandrosterone (DHEA), the major precursor of androgens and estrogens, has several beneficial effects on the immune system, on memory function, and in modulating the effects of diabetes, obesity, and chemical carcinogenesis. Treatment of rats with DHEA influences expression of cytochrome P450 (P450) genes, including peroxisome proliferator-activated receptor α (PPARα)- and pregnane X receptor (PXR)-mediated induction of CYP4As and CYP3A23, and suppression of CYP2C11. DHEA treatment elevated the expression and activities of CYP3A4, CYP2C9, CYP2C19, and CYP2B6 in primary cultures of human hepatocytes. Induction of CYP3A4 in human hepatocytes was consistent with studies in rats, but induction of CYP2Cs was unexpected. The role of PXR in this response was studied in transient transfection assays. DHEA activated hPXR in a concentration-dependent manner. Because CYP2B6 induction by DHEA in human hepatocytes might involve either PXR or constitutive androstane receptor (CAR) activation, we performed experiments in primary hepatocytes from CAR knockout mice and observed that CAR was required for maximal induction of Cyp2b10 by DHEA. Furthermore, CAR-mediated Cyp2b10 induction by DHEA was inhibited by the inverse agonist of CAR, androstanol (5α-androstan-3α-ol). Further evidence for CAR activation was provided by cytoplasmic/nuclear transfer of CAR upon DHEA treatment. Elucidation of CAR activation and subsequent induction of CYP2B6 by DHEA presented an additional mechanism by which the sterol can modify the expression of P450s. The effect of DHEA on the activation of the xenosensors PPARα, PXR, and CAR, and the consequent potential for adverse drug/toxicant interactions should be considered in humans treated with this nutriceutical agent. PMID:17591676

  17. M2b Monocytes Provoke Bacterial Pneumonia and Gut Bacteria-Associated Sepsis in Alcoholics.

    PubMed

    Tsuchimoto, Yusuke; Asai, Akira; Tsuda, Yasuhiro; Ito, Ichiaki; Nishiguchi, Tomoki; Garcia, Melanie C; Suzuki, Sumihiro; Kobayashi, Makiko; Higuchi, Kazuhide; Suzuki, Fujio

    2015-12-01

    Chronic alcohol consumption markedly impairs host antibacterial defense against opportunistic infections. γ-irradiated NOD-SCID IL-2Rγ(null) mice inoculated with nonalcoholic PBMCs (control PBMC chimeras) resisted Klebsiella pneumonia and gut bacteria-associated sepsis, whereas the chimeras created with alcoholic PBMCs (alcoholic PBMC chimeras) were very susceptible to these infections. M1 monocytes (IL-12(+)IL-10(-)CD163(-)CD14(+) cells), major effector cells in antibacterial innate immunity, were not induced by a bacterial Ag in alcoholic PBMC cultures, and M2b monocytes (CCL1(+)CD163(+)CD14(+) cells), which predominated in alcoholic PBMCs, were shown to be inhibitor cells on the Ag-stimulated monocyte conversion from quiescent monocytes to M1 monocytes. CCL1, which functions to maintain M2b macrophage properties, was produced by M2b monocytes isolated from alcoholic PBMCs. These M2b monocytes reverted to quiescent monocytes (IL-12(-)IL-10(-)CCL1(-)CD163(-)CD14(+) cells) in cultures supplemented with CCL1 antisense oligodeoxynucleotide, and the subsequent quiescent monocytes easily converted to M1 monocytes under bacterial Ag stimulation. Alcoholic PBMC chimeras treated with CCL1 antisense oligodeoxynucleotide were resistant against pulmonary infection by K. pneumoniae and sepsis stemming from enterococcal translocation. These results indicate that a majority of monocytes polarize to an M2b phenotype in association with alcohol abuse, and this polarization contributes to the increased susceptibility of alcoholics to gut and lung infections. Bacterial pneumonia and gut bacteria-associated sepsis, frequently seen in alcoholics, can be controlled through the polarization of macrophage phenotypes. PMID:26525287

  18. Atmospheric Circulation of Eccentric Hot Jupiter HAT-P-2b

    NASA Astrophysics Data System (ADS)

    Lewis, Nikole K.; Showman, Adam P.; Fortney, Jonathan J.; Knutson, Heather A.; Marley, Mark S.

    2014-11-01

    The hot Jupiter HAT-P-2b has become a prime target for Spitzer Space Telescope observations aimed at understanding the atmospheric response of exoplanets on highly eccentric orbits. Here we present a suite of three-dimensional atmospheric circulation models for HAT-P-2b that investigate the effects of assumed atmospheric composition and rotation rate on global scale winds and thermal patterns. We compare and contrast atmospheric models for HAT-P-2b, which assume one and five times solar metallicity, both with and without TiO/VO as atmospheric constituents. Additionally we compare models that assume a rotation period of half, one, and two times the nominal pseudo-synchronous rotation period. We find that changes in assumed atmospheric metallicity and rotation rate do not significantly affect model predictions of the planetary flux as a function of orbital phase. However, models in which TiO/VO are present in the atmosphere develop a transient temperature inversion between the transit and secondary eclipse events that results in significant variations in the timing and magnitude of the peak of the planetary flux compared with models in which TiO/VO are omitted from the opacity tables. We find that no one single atmospheric model can reproduce the recently observed full orbit phase curves at 3.6, 4.5 and 8.0 μm, which is likely due to a chemical process not captured by our current atmospheric models for HAT-P-2b. Further modeling and observational efforts focused on understanding the chemistry of HAT-P-2b's atmosphere are needed and could provide key insights into the interplay between radiative, dynamical, and chemical processes in a wide range of exoplanet atmospheres.

  19. Induction of the CYP2B genes by triphenyldioxane treatment in the rat liver.

    PubMed

    Grigorieva, E; Soshilov, A; Surovtseva, Y; Schwartz, E L; Duzhak, T G; Gulyaeva, L F; Lyakhovich, V V

    2002-08-01

    Triphenyldioxane (TPD) is a potent phenobarbital-type (PB) inducer of the CYP2B cytochrome isoforms, the inducing effect of which is one order of magnitude higher than PB. The fact that TPD is unable to induce CYP2B genes having the proximal promoter disrupted (mouse Cyp2b10) suggests an existence of the proximal promoter-dependent mechanism of the CYP2B induction. So a TPD-dependent activation of the nuclear proteins to the binding with Barbie-box sequence (the most conservative part of the proximal promoter) was studied. In the nuclear extracts from the intact rat liver there were detected five proteins that could be activated to the Barbie-box binding by the TPD treatment in vitro (II, III, NI, NII and NIII). The first three were effected also by another PB-like inducers tested (PB and TCPOBOP), when NII and NIII complexes were formed under the influence of TPD only. It is possible that a direct activation of the NII and NIII proteins by TPD exists as (3)H-labeled TPD was detected in the composition of NII and NIII complexes. However, both of them disappeared from the nuclear extracts after the long exposure time with TPD (6 h or more). A short induction by the direct intra-liver delivery of TPD (15-30 min) led to the stabile activation of one TPD-specific protein. Apart from the activation of the Barbie-box-binding protein, the short TPD treatment caused the activation of three nuclear proteins being able to interact with the NR1 sequence of the distal promoter PBREM element. These findings suggest that TPD is really the first member of the PB-like inducers family for which a special mechanism of CYP2B induction may exist. PMID:12110287

  20. The International Space Station 2B Photovoltaic Thermal Control System (PVTCS) Leak: An Operational History

    NASA Technical Reports Server (NTRS)

    Vareha, Anthony N.

    2014-01-01

    As early as 2004, the Photovoltaic Thermal Control System (PVTCS) for the International Space Station's 2B electrical power channel began slowly leaking ammonia overboard. Initially, the operations strategy was "feed the leak," a strategy successfully put into action via Extra Vehicular Activity (EVA) during the STS-134 Space Shuttle mission. This recharge was to have allowed for continued power channel operation into 2014 or 2015, at which point another EVA would have been required. In mid-2012, the leak rate increased from 1.5lbm/year to approximately 5lbm/year. As a result, an EVA was planned and executed within a 5 week timeframe to drastically alter the architecture of the PVTCS via connection to an adjacent dormant thermal control system. This EVA, US EVA 20, was successfully executed on November 1, 2012 and left the 2B PVTCS in a configuration where the system was now being adequately cooled via a different radiator than what the system was designed to utilize. Data monitoring over the next several months showed that the isolated radiator had not been leaking, and the system itself continued to leak steadily until May 9th, 2013. It was on this day that the ISS crew noticed the visible presence of ammonia crystals escaping from the 2B channel's truss segment, signifying a rapid acceleration of the leak from 5lbm/year to 5lbm/day. Within 48 hours of the crew noticing the leak, US EVA 21 was in progress to replace the coolant pump - the only remaining replaceable leak source. This was successful, and telemetry monitoring has shown that indeed the coolant pump was the leak source and was thus isolated from the running 2B PVTCS. This paper will explore the management of the 2B PVTCS leak from the operations perspective.

  1. Targeted deletion of titin N2B region leads to diastolic dysfunction and cardiac atrophy

    PubMed Central

    Radke, Michael H.; Peng, Jun; Wu, Yiming; McNabb, Mark; Nelson, O. Lynne; Granzier, Henk; Gotthardt, Michael

    2007-01-01

    Titin is a giant protein that is in charge of the assembly and passive mechanical properties of the sarcomere. Cardiac titin contains a unique N2B region, which has been proposed to modulate elasticity of the titin filament and to be important for hypertrophy signaling and the ischemic stress response through its binding proteins FHL2 and αB-crystallin, respectively. To study the role of the titin N2B region in systole and diastole of the heart, we generated a knockout (KO) mouse deleting only the N2B exon 49 and leaving the remainder of the titin gene intact. The resulting mice survived to adulthood and were fertile. Although KO hearts were small, they produced normal ejection volumes because of an increased ejection fraction. FHL2 protein levels were significantly reduced in the KO mice, a finding consistent with the reduced size of KO hearts. Ultrastructural analysis revealed an increased extension of the remaining spring elements of titin (tandem Ig segments and the PEVK region), which, together with the reduced sarcomere length and increased passive tension derived from skinned cardiomyocyte experiments, translates to diastolic dysfunction as documented by echocardiography. We conclude from our work that the titin N2B region is dispensable for cardiac development and systolic properties but is important to integrate trophic and elastic functions of the heart. The N2B-KO mouse is the first titin-based model of diastolic dysfunction and, considering the high prevalence of diastolic heart failure, it could provide future mechanistic insights into the disease process. PMID:17360664

  2. Atmospheric circulation of eccentric hot Jupiter HAT-P-2B

    SciTech Connect

    Lewis, Nikole K.; Showman, Adam P.; Fortney, Jonathan J.; Knutson, Heather A.; Marley, Mark S.

    2014-11-10

    The hot Jupiter HAT-P-2b has become a prime target for Spitzer Space Telescope observations aimed at understanding the atmospheric response of exoplanets on highly eccentric orbits. Here we present a suite of three-dimensional atmospheric circulation models for HAT-P-2b that investigate the effects of assumed atmospheric composition and rotation rate on global scale winds and thermal patterns. We compare and contrast atmospheric models for HAT-P-2b, which assume one and five times solar metallicity, both with and without TiO/VO as atmospheric constituents. Additionally we compare models that assume a rotation period of half, one, and two times the nominal pseudo-synchronous rotation period. We find that changes in assumed atmospheric metallicity and rotation rate do not significantly affect model predictions of the planetary flux as a function of orbital phase. However, models in which TiO/VO are present in the atmosphere develop a transient temperature inversion between the transit and secondary eclipse events that results in significant variations in the timing and magnitude of the peak of the planetary flux compared with models in which TiO/VO are omitted from the opacity tables. We find that no one single atmospheric model can reproduce the recently observed full orbit phase curves at 3.6, 4.5 and 8.0 μm, which is likely due to a chemical process not captured by our current atmospheric models for HAT-P-2b. Further modeling and observational efforts focused on understanding the chemistry of HAT-P-2b's atmosphere are needed and could provide key insights into the interplay between radiative, dynamical, and chemical processes in a wide range of exoplanet atmospheres.

  3. Nematode and Arthropod Genomes Provide New Insights into the Evolution of Class 2 B1 GPCRs

    PubMed Central

    Cardoso, João C. R.; Félix, Rute C.; Power, Deborah M.

    2014-01-01

    Nematodes and arthropods are the most speciose animal groups and possess Class 2 B1 G-protein coupled receptors (GPCRs). Existing models of invertebrate Class 2 B1 GPCR evolution are mainly centered on Caenorhabditis elegans and Drosophila melanogaster and a few other nematode and arthropod representatives. The present study reevaluates the evolution of metazoan Class 2 B1 GPCRs and orthologues by exploring the receptors in several nematode and arthropod genomes and comparing them to the human receptors. Three novel receptor phylogenetic clusters were identified and designated cluster A, cluster B and PDF-R-related cluster. Clusters A and B were identified in several nematode and arthropod genomes but were absent from D. melanogaster and Culicidae genomes, whereas the majority of the members of the PDF-R-related cluster were from nematodes. Cluster A receptors were nematode and arthropod-specific but shared a conserved gene environment with human receptor loci. Cluster B members were orthologous to human GCGR, PTHR and Secretin members with which they probably shared a common origin. PDF-R and PDF-R related clusters were present in representatives of both nematodes and arthropods. The results of comparative analysis of GPCR evolution and diversity in protostomes confirm previous notions that C. elegans and D. melanogaster genomes are not good representatives of nematode and arthropod phyla. We hypothesize that at least four ancestral Class 2 B1 genes emerged early in the metazoan radiation, which after the protostome-deuterostome split underwent distinct selective pressures that resulted in duplication and deletion events that originated the current Class 2 B1 GPCRs in nematode and arthropod genomes. PMID:24651821

  4. Deletion of ADORA2B from myeloid cells dampens lung fibrosis and pulmonary hypertension

    PubMed Central

    Karmouty-Quintana, Harry; Philip, Kemly; Acero, Luis F.; Chen, Ning-Yuan; Weng, Tingting; Molina, Jose G.; Luo, Fayong; Davies, Jonathan; Le, Ngoc-Bao; Bunge, Isabelle; Volcik, Kelly A.; Le, Thanh-Thuy T.; Johnston, Richard A.; Xia, Yang; Eltzschig, Holger K.; Blackburn, Michael R.

    2015-01-01

    Idiopathic pulmonary fibrosis (IPF) is a lethal, fibroproliferative disease. Pulmonary hypertension (PH) can develop secondary to IPF and increase mortality. Alternatively, activated macrophages (AAMs) contribute to the pathogenesis of both IPF and PH. Here we hypothesized that adenosine signaling through the ADORA2B on AAMs impacts the progression of these disorders and that conditional deletion of ADORA2B on myeloid cells would have a beneficial effect in a model of these diseases. Conditional knockout mice lacking ADORA2B on myeloid cells (Adora2Bf/f-LysMCre) were exposed to the fibrotic agent bleomycin (BLM; 0.035 U/g body weight, i.p.). At 14, 17, 21, 25, or 33 d after exposure, SpO2, bronchoalveolar lavage fluid (BALF), and histologic analyses were performed. On day 33, lung function and cardiovascular analyses were determined. Markers for AAM and mediators of fibrosis and PH were assessed. Adora2Bf/f-LysMCre mice presented with attenuated fibrosis, improved lung function, and no evidence of PH compared with control mice exposed to BLM. These findings were accompanied by reduced expression of CD206 and arginase-1, markers for AAMs. A 10-fold reduction in IL-6 and a 5-fold decrease in hyaluronan, both linked to lung fibrosis and PH, were also observed. These data suggest that activation of the ADORA2B on macrophages plays an active role in the pathogenesis of lung fibrosis and PH.—Karmouty-Quintana, H., Philip, K., Acero, L. F., Chen, N.-Y., Weng, T., Molina, J. G., Luo, F., Davies, J., Le, N.-B., Bunge, I., Volcik, K. A., Le, T.-T. T., Johnston, R. A., Xia, Y., Eltzschig, H. K., Blackburn, M. R. Deletion of ADORA2B from myeloid cells dampens lung fibrosis and pulmonary hypertension. PMID:25318478

  5. Effect of tamoxifen on the enzymatic activity of human cytochrome CYP2B6.

    PubMed

    Sridar, Chitra; Kent, Ute M; Notley, Lisa M; Gillam, Elizabeth M J; Hollenberg, Paul F

    2002-06-01

    Tamoxifen is primarily used in the treatment of breast cancer. It has been approved as a chemopreventive agent for individuals at high risk for this disease. Tamoxifen is metabolized to a number of different products by cytochrome P450 enzymes. The effect of tamoxifen on the enzymatic activity of bacterially expressed human cytochrome CYP2B6 in a reconstituted system has been investigated. The 7-ethoxy-4-(trifluoromethyl)coumarin O-deethylation activity of purified CYP2B6 was inactivated by tamoxifen in a time- and concentration-dependent manner. Enzymatic activity was lost only in samples that were incubated with both tamoxifen and NADPH. The inactivation was characterized by a K(I) of 0.9 microM, a k(inact) of 0.02 min(-1), and a t(1/2) of 34 min. The loss in the 7-ethoxy-4-(trifluoromethyl)coumarin O-deethylation activity did not result in a similar percentage loss in the reduced carbon monoxide spectrum, suggesting that the heme moiety was not the major site of modification. The activity of CYP2B6 was not recovered after removal of free tamoxifen using spin column gel filtration. The loss in activity seemed to be due to a modification of the CYP2B6 and not reductase because adding fresh reductase back to the inactivated samples did not restore enzymatic activity. A reconstituted system containing purified CYP2B6, NADPH-reductase, and NADPH-generating system was found to catalyze tamoxifen metabolism to 4-OH-tamoxifen, 4'-OH-tamoxifen, and N-desmethyl-tamoxifen as analyzed by high-performance liquid chromatography analysis. Preliminary studies showed that tamoxifen had no effect on the activities of CYP1B1 and CYP3A4, whereas CYP2D6 and CYP2C9 exhibited a 25% loss in enzymatic activity. PMID:12023523

  6. Comparison of three commercial one-dose porcine circovirus type 2 (PCV2) vaccines in a herd with concurrent circulation of PCV2b and mutant PCV2b.

    PubMed

    Jeong, Jiwoon; Park, Changhoon; Choi, Kyuhyung; Chae, Chanhee

    2015-05-15

    Porcine circovirus associated disease (PCVAD) occurred in a farm where pigs had been routinely vaccinated with a commercial PCV2a vaccine. A mutant PCV2b (mPCV2b) was isolated from pigs with PCVAD, perhaps implying a perceived vaccine failure. The objective of this study was to determine and compare the efficacy of 3 one-dose PCV2a vaccines of varying antigen type and dose in the same pig farm with concurrent PCV2b and mPCV2b infection based on clinical (average daily weight gain; ADWG), virological (evidence of viremia), immunological (presence of PCV2-specific neutralizing antibody; NA and interferon-γ secreting cells; IFN-γ-SC), and pathological (lymphoid lesion and PCV2 antigen score within lesion) evaluation. Regardless of which commercial PCV2a vaccine was used, vaccinated animals improved ADWG, and reduced the amount of PCV2b and mPCV2b load in the blood compared to unvaccinated animals. The vaccination of piglets at 3 weeks of age effectively induced higher levels of PCV2b- and mPCV2b-specific NA and IFN-γ-SC compared to unvaccinated animals. A reduction in mPCV2b load in the blood coincided with the appearance of both mPCV2b-specific NA and IFN-γ-SC in the vaccinated animals. The microscopic lymphoid lesions and PCV2-antigen scores within the lymph nodes were significantly lower in vaccinated animals. The perceived vaccine failure could not be explained by incomplete protection of the commercial PCV2a vaccine against mPCV2b. The results of the present study demonstrated that currently available commercial PCV2a vaccines are protective against concurrent PCV2b and mPCV2b infection based on clinical, virological, immunological, and pathological evaluations under field conditions. PMID:25790733

  7. CMV2b-AGO Interaction Is Required for the Suppression of RDR-Dependent Antiviral Silencing in Arabidopsis

    PubMed Central

    Fang, Yuan-Yuan; Zhao, Jian-Hua; Liu, Shang-Wu; Wang, Sheng; Duan, Cheng-Guo; Guo, Hui-Shan

    2016-01-01

    Using a transient plant system, it was previously found that the suppression of Cucumber mosaic virus (CMV) 2b protein relies on its double-strand (ds) RNA binding capacity, but it is independent of its interaction with ARGONAUTE (AGO) proteins. Thus, the biological meaning of the 2b-AGO interaction in the context of virus infection remains elusive. In this study, we created infectious clones of CMV mutants that expressed the 2b functional domains of dsRNA or AGO binding and tested the effect of these CMV mutants on viral pathogenicity. We found that the mutant CMV2b(1–76) expressing the 2b dsRNA-binding domain exhibited the same virulence as wild-type CMV in infection with either wild-type Arabidopsis or rdr1/6 plants with RDR1- and RDR6-deficient mutations. However, remarkably reduced viral RNA levels and increased virus (v)siRNAs were detected in CMV2b(1–76)-infected Arabidopsis in comparison to CMV infection, which demonstrated that the 2b(1–76) deleted AGO-binding domain failed to suppress the RDR1/RDR6-dependent degradation of viral RNAs. The mutant CMV2b(8–111) expressing mutant 2b, in which the N-terminal 7 amino acid (aa) was deleted, exhibited slightly reduced virulence, but not viral RNA levels, in both wild-type and rdr1/6 plants, which indicated that 2b retained the AGO-binding activity acquired the counter-RDRs degradation of viral RNAs. The deletion of the N-terminal 7 aa of 2b affected virulence due to the reduced affinity for long dsRNA. The mutant CMV2b(18–111) expressing mutant 2b lacked the N-terminal 17 aa but retained its AGO-binding activity greatly reduced virulence and viral RNA level. Together with the instability of both 2b(18–111)-EGFP and RFP-AGO4 proteins when co-expressed in Nicotiana benthamiana leaves, our data demonstrates that the effect of 2b-AGO interaction on counter-RDRs antiviral defense required the presence of 2b dsRNA-binding activity. Taken together, our findings demonstrate that the dsRNA-binding activity of

  8. CMV2b-AGO Interaction Is Required for the Suppression of RDR-Dependent Antiviral Silencing in Arabidopsis.

    PubMed

    Fang, Yuan-Yuan; Zhao, Jian-Hua; Liu, Shang-Wu; Wang, Sheng; Duan, Cheng-Guo; Guo, Hui-Shan

    2016-01-01

    Using a transient plant system, it was previously found that the suppression of Cucumber mosaic virus (CMV) 2b protein relies on its double-strand (ds) RNA binding capacity, but it is independent of its interaction with ARGONAUTE (AGO) proteins. Thus, the biological meaning of the 2b-AGO interaction in the context of virus infection remains elusive. In this study, we created infectious clones of CMV mutants that expressed the 2b functional domains of dsRNA or AGO binding and tested the effect of these CMV mutants on viral pathogenicity. We found that the mutant CMV2b(1-76) expressing the 2b dsRNA-binding domain exhibited the same virulence as wild-type CMV in infection with either wild-type Arabidopsis or rdr1/6 plants with RDR1- and RDR6-deficient mutations. However, remarkably reduced viral RNA levels and increased virus (v)siRNAs were detected in CMV2b(1-76)-infected Arabidopsis in comparison to CMV infection, which demonstrated that the 2b(1-76) deleted AGO-binding domain failed to suppress the RDR1/RDR6-dependent degradation of viral RNAs. The mutant CMV2b(8-111) expressing mutant 2b, in which the N-terminal 7 amino acid (aa) was deleted, exhibited slightly reduced virulence, but not viral RNA levels, in both wild-type and rdr1/6 plants, which indicated that 2b retained the AGO-binding activity acquired the counter-RDRs degradation of viral RNAs. The deletion of the N-terminal 7 aa of 2b affected virulence due to the reduced affinity for long dsRNA. The mutant CMV2b(18-111) expressing mutant 2b lacked the N-terminal 17 aa but retained its AGO-binding activity greatly reduced virulence and viral RNA level. Together with the instability of both 2b(18-111)-EGFP and RFP-AGO4 proteins when co-expressed in Nicotiana benthamiana leaves, our data demonstrates that the effect of 2b-AGO interaction on counter-RDRs antiviral defense required the presence of 2b dsRNA-binding activity. Taken together, our findings demonstrate that the dsRNA-binding activity of the 2b was

  9. Capsid proteins from PCV2a genotype confer greater protection against a PCV2b strain than those from PCV2b genotype in pigs: evidence for PCV2b strains becoming more predominant than PCV2a strains from 2000 to 2010s.

    PubMed

    Huang, Liping; Wang, Yiping; Wei, Yanwu; Chen, Dongjie; Liu, Dan; Du, Wenjuan; Xia, Deli; Wu, Hongli; Feng, Li; Liu, Changming

    2016-07-01

    Two major porcine circovirus type 2 (PCV2) genotypes, PCV2a and PCV2b, are recognized. PCV2a was predominant in the global pig population until 2000 while PCV2b became predominant from 2003 onward. The aim of this study was to analyze the immune protection conferred by two PCV2a and two PCV2b capsid proteins (Caps) in pigs challenged with a mutant PCV2b/YJ (mPCV2b/YJ) strain. Pigs vaccinated with PCV2a/LG-Cap and PCV2a/CL-Cap elicited significantly higher levels of PCV2-specific antibodies and neutralizing antibodies compared with PCV2b/JF-Cap and mPCV2b/YJ-Cap. Following a mPCV2b/YJ challenge, no viremia was detected in the PCV2a/LG-Cap and PCV2a/CL-Cap groups, while viremias were found in 20 and 40 % of the pigs in the PCV2b/JF-Cap and mPCV2b/YJ-Cap groups, respectively. Viral loads in the inguinal lymph nodes of pigs from the PCV2b/JF-Cap and mPCV2b/YJ-Cap groups were significantly higher than those in the PCV2a/LG-Cap and PCV2a/CL-Cap groups, but significantly lower than those of the challenge control group. Furthermore, PCV2 antigens were not detected in the inguinal lymph nodes of pigs from commercial vaccine groups, as well as the PCV2a/LG-Cap and PCV2a/CL-Cap groups, but were found in the challenge control (100 %, 5/5), PCV2b/JF-Cap (20 %, 1/5), and mPCV2b/YJ-Cap (20 %, 1/5) groups. These findings suggest that mPCV2b/YJ-Cap and PCV2b/JF-Cap were less immunogenic than PCV2a/LG-Cap and PCV2a/CL-Cap. We speculate that a genotypic shift from PCV2a to PCV2b might be the result of the majority of PCV2a strains being more immunogenic than the majority of PCV2b strains. These results provide a possible explanation for why PCV2b strains are more likely to cause epidemics than PCV2a strains. It tells us that PCV2 pathogenesis may be associated with its immunogenicity to some extent. PMID:27020283

  10. Preclinical studies on targeted delivery of multiple IFNα2b to HLA-DR in diverse hematologic cancers.

    PubMed

    Rossi, Edmund A; Rossi, Diane L; Cardillo, Thomas M; Stein, Rhona; Goldenberg, David M; Chang, Chien-Hsing

    2011-08-18

    The short circulating half-life and side effects of IFNα affect its dosing schedule and efficacy. Fusion of IFNα to a tumor-targeting mAb (mAb-IFNα) can enhance potency because of increased tumor localization and improved pharmacokinetics. We used the Dock-and-Lock method to generate C2-2b-2b, a mAb-IFNα comprising tetrameric IFNα2b site-specifically linked to hL243 (humanized anti-HLA-DR). In vitro, C2-2b-2b inhibited various B-cell lymphoma leukemia and myeloma cell lines. In most cases, this immunocytokine was more effective than CD20-targeted mAb-IFNα or a mixture comprising the parental mAb and IFNα. Our findings indicate that responsiveness depends on HLA-DR expression/density and sensitivity to IFNα and hL243. C2-2b-2b induced more potent and longer-lasting IFNα signaling compared with nontargeted IFNα. Phosphorylation of STAT1 was more robust and persistent than that of STAT3, which may promote apoptosis. C2-2b-2b efficiently depleted lymphoma and myeloma cells from whole human blood but also exhibited some toxicity to B cells, monocytes, and dendritic cells. C2-2b-2b showed superior efficacy compared with nontargeting mAb-IFNα, peginterferonalfa-2a, or a combination of hL243 and IFNα, using human lymphoma and myeloma xenografts. These results suggest that C2-2b-2b should be useful in the treatment of various hematopoietic malignancies. PMID:21680794

  11. Role of the A2B receptor–adenosine deaminase complex in colonic dysmotility associated with bowel inflammation in rats

    PubMed Central

    Antonioli, L; Fornai, M; Awwad, O; Giustarini, G; Pellegrini, C; Tuccori, M; Caputi, V; Qesari, M; Castagliuolo, I; Brun, P; Giron, M C; Scarpignato, C; Blandizzi, C; Colucci, R

    2014-01-01

    BACKGROUND AND PURPOSE Adenosine A2B receptors regulate several physiological enteric functions. However, their role in the pathophysiology of intestinal dysmotility associated with inflammation has not been elucidated. Hence, we investigated the expression of A2B receptors in rat colon and their role in the control of cholinergic motility in the presence of bowel inflammation. EXPERIMENTAL APPROACH Colitis was induced by 2,4-dinitrobenzenesulfonic acid (DNBS). Colonic A2B receptor expression and localization were examined by RT-PCR and immunofluorescence. The interaction between A2B receptors and adenosine deaminase was assayed by immunoprecipitation. The role of A2B receptors in the control of colonic motility was examined in functional experiments on longitudinal muscle preparations (LMPs). KEY RESULTS A2B receptor mRNA was present in colon from both normal and DNBS-treated rats but levels were increased in the latter. A2B receptors were predominantly located in the neuromuscular layer, but, in the presence of colitis, were increased mainly in longitudinal muscle. Functionally, the A2B receptor antagonist MRS 1754 enhanced both electrically-evoked and carbachol-induced cholinergic contractions in normal LMPs, but was less effective in inflamed tissues. The A2B receptor agonist NECA decreased colonic cholinergic motility, with increased efficacy in inflamed LMP. Immunoprecipitation and functional tests revealed a link between A2B receptors and adenosine deaminase, which colocalize in the neuromuscular compartment. CONCLUSIONS AND IMPLICATIONS Under normal conditions, endogenous adenosine modulates colonic motility via A2B receptors located in the neuromuscular compartment. In the presence of colitis, this inhibitory control is impaired due to a link between A2B receptors and adenosine deaminase, which catabolizes adenosine, thus preventing A2B receptor activation. PMID:24286264

  12. Changes in the Adult GluN2B Associated Proteome following Adolescent Intermittent Ethanol Exposure

    PubMed Central

    Swartzwelder, H. Scott; Risher, Mary-Louise; Miller, Kelsey M.; Colbran, Roger J.; Winder, Danny G.; Wills, Tiffany A.

    2016-01-01

    Adolescent alcohol use is the strongest predictor for alcohol use disorders. In rodents, adolescents have distinct responses to acute ethanol, and prolonged alcohol exposure during adolescence can maintain these phenotypes into adulthood. One brain region that is particularly sensitive to the effects of both acute and chronic ethanol exposure is the hippocampus. Adolescent intermittent ethanol exposure (AIE) produces long lasting changes in hippocampal synaptic plasticity and dendritic morphology, as well as in the susceptibility to acute ethanol-induced spatial memory impairment. Given the pattern of changes in hippocampal structure and function, one potential target for these effects is the ethanol sensitive GluN2B subunit of the NMDA receptor, which is known to be involved in synaptic plasticity and dendritic morphology. Thus we sought to determine if there were persistent changes in hippocampal GluN2B signaling cascades following AIE. We employed a previously validated GluN2B-targeted proteomic strategy that was used to identify novel signaling mechanisms altered by chronic ethanol exposure in the adult hippocampus. We collected adult hippocampal tissue (P70) from rats that had been given 2 weeks of AIE from P30-45. Tissue extracts were fractionated into synaptic and non-synaptic pools, immuno-precipitated for GluN2B, and then analyzed using proteomic methods. We detected a large number of proteins associated with GluN2B. AIE produced significant changes in the association of many proteins with GluN2B in both synaptic and non-synaptic fractions. Intriguingly the number of proteins changed in the non-synaptic fraction was double that found in the synaptic fraction. Some of these proteins include those involved in glutamate signaling cytoskeleton rearrangement, calcium signaling, and plasticity. Disruptions in these pathways may contribute to the persistent cellular and behavioral changes found in the adult hippocampus following AIE. Further, the robust change in

  13. Changes in the Adult GluN2B Associated Proteome following Adolescent Intermittent Ethanol Exposure.

    PubMed

    Swartzwelder, H Scott; Risher, Mary-Louise; Miller, Kelsey M; Colbran, Roger J; Winder, Danny G; Wills, Tiffany A

    2016-01-01

    Adolescent alcohol use is the strongest predictor for alcohol use disorders. In rodents, adolescents have distinct responses to acute ethanol, and prolonged alcohol exposure during adolescence can maintain these phenotypes into adulthood. One brain region that is particularly sensitive to the effects of both acute and chronic ethanol exposure is the hippocampus. Adolescent intermittent ethanol exposure (AIE) produces long lasting changes in hippocampal synaptic plasticity and dendritic morphology, as well as in the susceptibility to acute ethanol-induced spatial memory impairment. Given the pattern of changes in hippocampal structure and function, one potential target for these effects is the ethanol sensitive GluN2B subunit of the NMDA receptor, which is known to be involved in synaptic plasticity and dendritic morphology. Thus we sought to determine if there were persistent changes in hippocampal GluN2B signaling cascades following AIE. We employed a previously validated GluN2B-targeted proteomic strategy that was used to identify novel signaling mechanisms altered by chronic ethanol exposure in the adult hippocampus. We collected adult hippocampal tissue (P70) from rats that had been given 2 weeks of AIE from P30-45. Tissue extracts were fractionated into synaptic and non-synaptic pools, immuno-precipitated for GluN2B, and then analyzed using proteomic methods. We detected a large number of proteins associated with GluN2B. AIE produced significant changes in the association of many proteins with GluN2B in both synaptic and non-synaptic fractions. Intriguingly the number of proteins changed in the non-synaptic fraction was double that found in the synaptic fraction. Some of these proteins include those involved in glutamate signaling cytoskeleton rearrangement, calcium signaling, and plasticity. Disruptions in these pathways may contribute to the persistent cellular and behavioral changes found in the adult hippocampus following AIE. Further, the robust change in

  14. Reaction and reorientation of electronically excited H[sub 2](B)

    SciTech Connect

    Pibel, C.D.

    1992-09-01

    The room temperature rate (TR) constants for fluorescence quenching fluorescence of H[sub 2], HD, and D[sub 2] B [sup 1][Sigma][sub u][sup +] by [sup 4]He were measured as a function of the initially excited rotational and vibrational level of the hydrogen molecule, and the RT rate constants for molecular angular momentum reorientation of H[sub 2], HD and D[sub 2] (B [sup 1][Sigma][sub u][sup +]. v[prime]=0, J[prime]=1, M[sub J]=0) in collisions with He, Ne, Ar and H[sub 2](X [sup 1][Sigma][sub g][sup +]) were also measured. Vibrational state dependence of the quenching cross sections fits a vibrationally adiabatic model of the quenching process. From the vibrational state dependence of the quenching cross section, the barrier height for the quenching reaction is found to be 250[plus minus]40 cm[sup [minus]1], and the difference in the H-H stretching frequencies between H[sub 2](B) and the H[sub 2]-He complex at the barrier to reaction is 140[plus minus]80 cm[sup [minus]1]. The effective cross sections for angular momentum reorientation in collisions of H[sub 2], HD, D[sub 2] with He and Ne were found to be about 30 [Angstrom][sup 2] and were nearly the same for each isotope and with He and Ne as collision partners. Cross sections forreorientation of HD and D[sub 2] in collisions with Ar were 10.6[plus minus]2.0 and 13.9[plus minus]3.0 [Angstrom][sup 2], respectively. Reorientation of D[sub 2](B) in collisions with room temperature H[sub 2](X) occurs with a 7.6[plus minus]3.4 [Angstrom][sup 2] cross section. Calculated cross sections using semiclassical and quantum close coupled methods give cross sections for reorientation of H[sub 2](B) and D[sub 2](B) in collisions with He that agree quantitatively with experiment. Discrepancy between the calculated and experimental cross sections for HD(B)-HE are likely due to rotational relaxation in HD a Turbo PASCAL version of the data-taking program is included.

  15. Reaction and reorientation of electronically excited H{sub 2}(B)

    SciTech Connect

    Pibel, C.D.

    1992-09-01

    The room temperature rate (TR) constants for fluorescence quenching fluorescence of H{sub 2}, HD, and D{sub 2} B {sup 1}{Sigma}{sub u}{sup +} by {sup 4}He were measured as a function of the initially excited rotational and vibrational level of the hydrogen molecule, and the RT rate constants for molecular angular momentum reorientation of H{sub 2}, HD and D{sub 2} (B {sup 1}{Sigma}{sub u}{sup +}. v{prime}=0, J{prime}=1, M{sub J}=0) in collisions with He, Ne, Ar and H{sub 2}(X {sup 1}{Sigma}{sub g}{sup +}) were also measured. Vibrational state dependence of the quenching cross sections fits a vibrationally adiabatic model of the quenching process. From the vibrational state dependence of the quenching cross section, the barrier height for the quenching reaction is found to be 250{plus_minus}40 cm{sup {minus}1}, and the difference in the H-H stretching frequencies between H{sub 2}(B) and the H{sub 2}-He complex at the barrier to reaction is 140{plus_minus}80 cm{sup {minus}1}. The effective cross sections for angular momentum reorientation in collisions of H{sub 2}, HD, D{sub 2} with He and Ne were found to be about 30 {Angstrom}{sup 2} and were nearly the same for each isotope and with He and Ne as collision partners. Cross sections forreorientation of HD and D{sub 2} in collisions with Ar were 10.6{plus_minus}2.0 and 13.9{plus_minus}3.0 {Angstrom}{sup 2}, respectively. Reorientation of D{sub 2}(B) in collisions with room temperature H{sub 2}(X) occurs with a 7.6{plus_minus}3.4 {Angstrom}{sup 2} cross section. Calculated cross sections using semiclassical and quantum close coupled methods give cross sections for reorientation of H{sub 2}(B) and D{sub 2}(B) in collisions with He that agree quantitatively with experiment. Discrepancy between the calculated and experimental cross sections for HD(B)-HE are likely due to rotational relaxation in HD a Turbo PASCAL version of the data-taking program is included.

  16. Photoelectron Spectroscopy Study of [Ta2B6]-: a Hexagonal Bipyramdial Cluster

    NASA Astrophysics Data System (ADS)

    Jian, Tian; Li, Weili; Romanescu, Constantin; Wang, Lai-Sheng

    2014-06-01

    It has been a long-sought goal in cluster science to discover stable atomic clusters as building blocks for cluster-assembled nanomaterials, as exemplified by the fullerenes and their subsequent bulk syntheses.[1,2] Clusters have also been considered as models to understand bulk properties, providing a bridge between molecular and solid-state chemistry.[3] Herein we report a joint photoelectron spectroscopy and theoretical study on the [Ta2B6]- and [Ta2B6] clusters.[4] The photoelectron spectrum of [Ta2B6]- displays a simple spectral pattern and a large HOMO-LUMO gap, suggesting its high symmetry. Theoretical calculations show that both the neutral and anion are D6h pyramidal. The chemical bonding analyses for [Ta2B6] revealed the nature of the B6 and Ta interactions and uncovered strong covalent bonding between B6 and Ta. The D6h-[TaB6Ta] gaseous cluster is reminiscent of the structural pattern in the ReB6X6Re core in the [(Cp*Re)2B6H4Cl2] and the TiB6Ti motif in the newly synthesized Ti7Rh4Ir2B8 solid-state compound.[5,6] The current work provides an intrinsic link between a gaseous cluster and motifs for solid materials. Continued investigations of the transition-metal boron clusters may lead to the discovery of new structural motifs involving pure boron clusters for the design of novel boride materials. Reference [1] H.W. Kroto, J. R. Heath, S. C. OBrien, R. F. Curl, R. E. Smalley, Nature 1985, 318, 162 - 163. [2] W. Krtschmer, L. D. Lamb, K. Fostiropoulos, D. R. Huffman, Nature 1990, 347, 354 - 358. [3] T. P. Fehlner, J.-F. Halet, J.-Y. Saillard, Molecular Clusters: A Bridge to Solid-State Chemitry, Cambridge University Press, UK, 2007. [4] W. L. Li, L. Xie, T. Jian, C. Romanescu, X. Huang, L.-S. Wang, Angew. Chem. Int. Ed. 2014, 126, 1312 - 1316. [5] B. Le Guennic, H. Jiao, S. Kahlal, J.-Y. Saillard, J.-F. Halet, S. Ghosh, M. Shang, A. M. Beatty, A. L. Rheingold, T. P. Fehlner, J. Am. Chem. Soc. 2004, 126, 3203 - 3217. [6] B. P. T. Fokwa, M. Hermus, Angew

  17. Antimicrobial action of histone H2B in Escherichia coli: evidence for membrane translocation and DNA-binding of a histone H2B fragment after proteolytic cleavage by outer membrane proteinase T.

    PubMed

    Kawasaki, Hiroaki; Koyama, Takumi; Conlon, J Michael; Yamakura, Fumiyuki; Iwamuro, Shawichi

    2008-01-01

    Previous studies have led to the isolation of histone H2B with antibacterial properties from an extract of the skin of the Schlegel's green tree frog Rhacophorus schlegelii and it is now demonstrated that the intact peptide is released into norepinephrine-stimulated skin secretions. In order to investigate the mechanism of action of this peptide, a maltose-binding protein (MBP)-fused histone H2B (MBP-H2B) conjugate was prepared and subjected to antimicrobial assay. The fusion protein showed bacteriostatic activity against Escherichia coli strain JCM5491 with a minimum inhibitory concentration of 11 microM. The lysate prepared from JCM5491 cells was capable of fragmenting MBP-H2B within the histone H2B region, but the lysate from the outer membrane proteinase T (OmpT) gene-deleted BL21(DE3) cells was not. FITC-labeled MBP-H2B (FITC-MBP-H2B) penetrated into the bacterial cell membrane of JCM5491 and ompT-transformed BL21(DE3) cells, but not into ompT-deleted BL21(DE3) cells. Gel retardation assay using MBP-H2B-deletion mutants indicated that MBP-H2B bound to DNA at a site within the N-terminal region of histone H2B. Consequently, it is proposed that the antimicrobial action of histone H2B involves, at least in part, penetration of an OmpT-produced N-terminal histone H2B fragment into the bacterial cell membrane with subsequent inhibition of cell functions. PMID:18706965

  18. Volkszählung und Mikrozensus1

    NASA Astrophysics Data System (ADS)

    Grohmann, Heinz

    Die Volkszählung (Zensus) ist seit langem weltweit eine statistische Erhebung über Bevölkerung und Erwerbstätigkeit. In vielen Ländern wird sie heute in etwa 10jährigem Abstand durchgeführt. In Deutschland wurde sie in den 80er Jahren zum Politikum. Datenschutzängste, verbunden mit politischen Vorgängen (Friedensbewegung), erregten die Menschen, und das Bundesverfassungsgericht steckte neue Grenzen ab. Nach kontroversen Auseinandersetzungen, an denen die Deutsche Statistische Gesellschaft (DStatG) konstruktiv beteiligt war, kam es zur Volkszählung 1987. Den nachfolgenden Paradigmenwechsel hin zu einem registergestützten Zensus 2011 hat die DStatG ebenfalls kreativ mitgestaltet. Im Beitrag wird dieser Weg nachgezeichnet. Das neue Konzept wird vorgestellt und kritisch gewürdigt. Betroffen war auch der Mikrozensus als größte Bevölkerungs- und Arbeitsmarktstichprobe zwischen den Zensen. Nicht zuletzt durch das Wirken eines wissenschaftlichen Beirats, dessen Mitglieder von der DStatG vorgeschlagen wurden, blieb diese Erhebung in ihrem Kern für die Zukunft erhalten.

  19. Superconductivity of magnetic Sm-substituted LaCo{sub 2}B{sub 2}

    SciTech Connect

    Wang, Y.; Ren, W. J. Duan, T. F.; Li, D.; Li, J.; Zhang, Z. D.

    2015-05-07

    In this work, superconductivity with a maximum superconducting transition onset temperature T{sub C} of 3.6 K is reported in La{sub 1-x}Sm{sub x}Co{sub 2}B{sub 2} in the concentration range 0.12 ≤ x ≤ 0.20. Substitution of magnetic Sm ions with 4f electrons for La is beneficial for superconductivity in the system. The low upper critical field of La{sub 0.8}Sm{sub 0.2}Co{sub 2}B{sub 2} suggests that the dominant magnetic-field suppressing superconducting mechanism is the orbit pair-breaking effect. A special specific-heat anomaly is observed around T{sub C}.

  20. Abraham Lincoln's marfanoid mother: the earliest known case of multiple endocrine neoplasia type 2B?

    PubMed

    Sotos, John G

    2012-07-01

    The nature and cause of President Abraham Lincoln's unusual physical features have long been debated, with the greatest attention directed at two monogenic disorders of the transforming growth factor β system: Marfan syndrome and multiple endocrine neoplasia type 2B. The present report examines newly discovered phenotypic information about Lincoln's biological mother, Nancy Hanks Lincoln, and concludes that (a) Lincoln's mother was skeletally marfanoid, (b) the President and his mother were highly concordant for the presence of numerous facial features found in various transforming growth factor β disorders, and (c) Lincoln's mother, like her son, had hypotonic skeletal muscles, resulting in myopathic facies and 'pseudodepression'. These conclusions establish that mother and son had the same monogenic autosomal dominant marfanoid disorder. A description of Nancy Hanks Lincoln as coarse-featured, and a little-known statement that a wasting disease contributed to her death at age 34, lends support to the multiple endocrine neoplasia type 2B hypothesis. PMID:22504423

  1. Populating the i2b2 database with heterogeneous EMR data: a semantic network approach.

    PubMed

    Mate, Sebastian; Bürkle, Thomas; Köpcke, Felix; Breil, Bernhard; Wullich, Bernd; Dugas, Martin; Prokosch, Hans-Ulrich; Ganslandt, Thomas

    2011-01-01

    In an ongoing effort to share heterogeneous electronic medical record (EMR) data in an i2b2 instance between the University Hospitals Münster and Erlangen for joint cancer research projects, an ontology based system for the mapping of EMR data to a set of common data elements has been developed. The system translates the mappings into local SQL scripts, which are then used to extract, transform and load the facts data from each EMR into the i2b2 database. By using Semantic Web standards, it is the authors' goal to reuse the laboriously compiled "mapping knowledge" in future projects, such as a comprehensive cancer ontology or even a hospital-wide clinical ontology. PMID:21893800

  2. Convoluted nozzle design for the RL10 derivative 2B engine

    NASA Technical Reports Server (NTRS)

    1985-01-01

    The convoluted nozzle is a conventional refractory metal nozzle extension that is formed with a portion of the nozzle convoluted to show the extendible nozzle within the length of the rocket engine. The convoluted nozzle (CN) was deployed by a system of four gas driven actuators. For spacecraft applications the optimum CN may be self-deployed by internal pressure retained, during deployment, by a jettisonable exit closure. The convoluted nozzle is included in a study of extendible nozzles for the RL10 Engine Derivative 2B for use in an early orbit transfer vehicle (OTV). Four extendible nozzle configurations for the RL10-2B engine were evaluated. Three configurations of the two position nozzle were studied including a hydrogen dump cooled metal nozzle and radiation cooled nozzles of refractory metal and carbon/carbon composite construction respectively.

  3. Incommensurate spin-density-wave antiferromagnetism in CeRu2Al2B

    NASA Astrophysics Data System (ADS)

    Bhattacharyya, A.; Khalyavin, D. D.; Krüger, F.; Adroja, D. T.; Strydom, A. M.; Kockelmann, W. A.; Hillier, A. D.

    2016-02-01

    The newly discovered Ising-type ferromagnet CeRu2Al2B exhibits an additional phase transition at TN=14.2 K before entering the ferromagnetic ground state at TC=12.8 K. We clarify the nature of this transition through high resolution neutron diffraction measurements. The data reveal the presence of a longitudinal incommensurate spin-density wave (SDW) in the temperature range of TC2B a particularly attractive model system to study the global phase diagram of ferromagnetic heavy-fermion metals under the influence of magnetic frustration.

  4. Genetic characterization of a noncytopathic bovine viral diarrhea virus 2b isolated from cattle in China.

    PubMed

    Wang, Wei; Shi, Xinchuan; Chen, Chaoyang; Wu, Hua

    2014-10-01

    In January 2013, several clinical signs of cattle with diarrhea, cough, nasal discharge, and fever were reported in Jilin province, China. One virus named SD1301 was isolated and identified. Complete genome of the virus is 12258nt in length and contains a 5'UTR, one open reading frame encoding a polyprotein of 3,897 amino acids and a 3'UTR. Phylogenetic analysis of 5'UTR, N(pro), E1 and E2 gene demonstrated the virus belonged to BVDV 2b, and genetically related to the BVDV strain Hokudai-Lab/09 from Japan in 2010. This bovine viral diarrhea virus displays a unique genetic signature with 27-nucleotide deletion in the 5'UTR, which is similar to the bovine viral diarrhea virus C413 (AF002227). This was the first confirmed isolation of ncp BVDV2b circulating in bovine herd of China. PMID:24811746

  5. Modeling the High Speed Research Cycle 2B Longitudinal Aerodynamic Database Using Multivariate Orthogonal Functions

    NASA Technical Reports Server (NTRS)

    Morelli, E. A.; Proffitt, M. S.

    1999-01-01

    The data for longitudinal non-dimensional, aerodynamic coefficients in the High Speed Research Cycle 2B aerodynamic database were modeled using polynomial expressions identified with an orthogonal function modeling technique. The discrepancy between the tabular aerodynamic data and the polynomial models was tested and shown to be less than 15 percent for drag, lift, and pitching moment coefficients over the entire flight envelope. Most of this discrepancy was traced to smoothing local measurement noise and to the omission of mass case 5 data in the modeling process. A simulation check case showed that the polynomial models provided a compact and accurate representation of the nonlinear aerodynamic dependencies contained in the HSR Cycle 2B tabular aerodynamic database.

  6. Electronic structure study of TiB{sub 2} and Ti{sub 2}B

    SciTech Connect

    Vashistha, M. Vyas, V.; Kabra, K.; Sharma, G.

    2015-06-24

    In this paper, the electronic properties of TiB{sub 2} and Ti{sub 2}B are computed within the framework of Density Functional Theory (DFT) based on Linear Combination of Atomic Orbitals (LCAO) method. In the present calculations, the generalized gradient approximation (GGA) proposed by Perdew-Burke-Erenzerhof (PBE) and Becke’s scheme are considered to treat the correlation and exchange effects respectively. TiB{sub 2} crystallizes in the hexagonal AlB{sub 2} type structure which is designated as C32 with the space group P6/mmm. While the crystal structure of Ti{sub 2}B described in this paper is isomorphous to the body centered tetragonal (Al{sub 2}Cu - type) structure with space group I4/mcm.

  7. Structural field of K2Al2B2O7-family crystals

    NASA Astrophysics Data System (ADS)

    Atuchin, Victor V.; Bazarov, Bair G.; Grossman, Victoria G.; Molokeev, Maxim S.; Bazarova, Zhibzema G.

    2013-05-01

    The known crystal structures of borate compounds with general composition AI 2MIII 2B2O7 (AI: Na, K, Cs, Rb) have been considered. The structures in space groups P63/m, P-31c, P321 and P21/c have been found depending on cation combination. Criterion k = (r(MIII)+r(B)+2r(O))/r(AI) has been formulated and it controls the formation of trigonal K2Al2B2O7 (KABO) type structure. The existence of noncentrosymmetric KABO-type borates is possible over the range of k = 2.7 - 2.06. This range is promising for searching new borate crystals and solid solutions with pronounced nonlinear optical properties.

  8. Modeling viral and drug kinetics: hepatitis C virus treatment with pegylated interferon alfa-2b.

    PubMed

    Powers, Kimberly A; Dixit, Narendra M; Ribeiro, Ruy M; Golia, Preeti; Talal, Andrew H; Perelson, Alan S

    2003-01-01

    Administration of peginterferon alfa-2b plus ribavirin results in an early hepatitis C virus (HCV) RNA decay followed by an increase as the drug concentration declines between doses. Upon administration of the next dose 1 week later, the same pattern is observed. We have incorporated pharmacokinetic/pharmacodynamic analysis into a model of viral dynamics to describe the effect that changes in drug concentration and effectiveness can have on viral levels. To illustrate the relationship between pharmacokinetics and viral dynamics, we fit the model to data from four HCV/human immunodeficiency virus co-infected patients, and obtained good agreement with the measured serum HCV RNA levels. We were able to account for the observed increases in HCV RNA, and estimate virion and drug half-lives that are in agreement with previous reports. Models incorporating pharmacokinetics are needed to correctly interpret viral load changes and estimate drug effectiveness in treatment protocols using peginterferon alfa-2b. PMID:12934163

  9. XO-2b: A Transiting Hot Jupiter in a Metal-rich Common Proper Motion Binary

    NASA Astrophysics Data System (ADS)

    Burke, Christopher J.; McCullough, P. R.; Valenti, J. A.; Summers, F. J.; Stys, J. E.; Johns-Krull, C. M.; Janes, K. A.; Heasley, J. N.; Bissinger, R.; Fleenor, M.; Foote, C. N.; Garcia-Melendo, E.; Gary, B. L.; Howell, P. J.; Mallia, F.; Masi, G.; Vanmunster, T.

    2007-05-01

    XO-2b, the second transiting extrasolar planet from the XO Project (McCullough et al. 2005), is approximately Jupiter-size and 0.6 Jupiter-mass with an orbital period of 2.6 days. The stellar host, XO-2, is a V=11.2, early K dwarf which is metal rich, [Fe/H]=+0.44. XO-2 has a high proper motion, 157 mas/yr, and has a common proper motion stellar companion with half arcmin separation. The two stars are nearly identical twins, with very similar spectra and apparent magnitudes. The global network of amateur and professional astronomers organized by the XO project confirmed the XO-2b transit light curve two days after being notified that it was a high-priority candidate, and radial velocities confirmed its planetary mass eight days after that.

  10. H2B Ubiquitylation Modulates Spliceosome Assembly and Function in Budding Yeast

    PubMed Central

    Hérissant, Lucas; Moehle, Erica A.; Bertaccini, Diego; Van Dorsselaer, Alain; Schaeffer-Reiss, Christine; Guthrie, Christine; Dargemont, Catherine

    2014-01-01

    Background information Commitment to splicing occurs co-transcriptionally, but a major unanswered question is the extent to which various modifications of chromatin, the template for transcription in vivo, contribute to the regulation of splicing. Results Here we perform genome-wide analyses showing that inhibition of specific marks – H2B ubiquitylation, H3K4 methylation, and H3K36 methylation – perturbs splicing in budding yeast, with each modification exerting gene-specific effects. Furthermore, semi-quantitative mass spectrometry on purified nuclear mRNPs and chromatin immunoprecipitation analysis on intron-containing genes indicated that H2B ubiquitylation, but not Set1-, Set2- or Dot1-dependent H3 methylation, stimulates recruitment of the early splicing factors, namely U1 and U2 snRNPs, onto nascent RNAs. Conclusions These results suggest that histone modifications impact splicing of distinct subsets of genes using distinct pathways. PMID:24476359

  11. Indolo[3,2-b]quinolines: Synthesis, Biological Evaluation and Structure Activity-Relationships

    PubMed Central

    Kumar, Eyunni V.K. Suresh; Etukala, Jagan R.; Ablordeppey, Seth Y.

    2013-01-01

    The tetracyclic indolo[3,2-b]quinoline ring system constitutes an important structural moiety in natural products exhibiting numerous biological activities. In particular, indolo [3, 2-b]quinoline, commonly known as linear quindo-line is of particular interest, because of its rigid structure and scope of derivatization. Although the core linear quindoline skeleton shows little or no activity in several biological systems, introduction of a methyl group on the N-5 atom leading to cryptolepine induces remarkable activity against a broad spectrum of biological targets. A number of analogs of quindoline and cryptolepine have been synthesized, incorporating various functional groups on the core quindoline skeleton leading to improved biological activities. In this review, we describe various synthetic methodologies leading to the quindoline scaffold, the biological activities and the structure activity relationships (SAR) of quindoline derivatives toward different disease states to give a better picture of the importance of this moiety in medicinal chemistry. PMID:18537709

  12. Thermal neutron response of the Li 2B 4O 7:Cu TL dosimeter

    NASA Astrophysics Data System (ADS)

    Gauld, I. C.; Harvey, J. W.; Kennett, T. J.; Prestwich, W. V.

    1986-10-01

    A measurement of the thermal neutron response of the Li 2B 4O 7:Cu TLD has been conducted. The results obtained using the Panasonic UD-806 dosimeter and UD-854A holder yield a free-in-air response of 3.3±0.1 R 60Co equivalent per mSv of thermal neutrons. A thermal neutron response of over 7 R 60Co equivalent per mSv was observed when the dosimeter was irradiated on water phantoms. The high sensitivity may result in a substantial overestimate of the gamma dose equivalent if the TLD is used in a mixed neutron and gamma environment of unknown ratio. Measurements of the Li 2B 4O 7:Cu glow curve, TL saturation curve and the thermal neutron response dependence of the dosimeter filtration thickness are also presented.

  13. Tissue diagnosis of intestinal microsporidiosis using a fluorescent stain with Uvitex 2B.

    PubMed Central

    Franzen, C; Müller, A; Salzberger, B; Fätkenheuer, G; Eidt, S; Mahrle, G; Diehl, V; Schrappe, M

    1995-01-01

    AIMS--To detect intestinal microsporidiosis in paraffin wax embedded biopsy specimens using a fluorescence technique incorporating optical brighteners. METHODS--Eight HIV infected patients with confirmed intestinal microsporidiosis (six with Enterocytozoon bieneusi, one with Encephalitozoon intestinalis and one with Encephalitozoon cuniculi infection) and 10 without infection were studied. Tissue sections of paraffin wax embedded duodenal biopsy specimens were stained with 1% Uvitex 2B, coded and analysed independently by two investigators. RESULTS--In all eight cases with confirmed intestinal microsporidian infection, spores could be detected easily in tissue sections using the fluorescence technique. Spores or other elements consistent with microsporidiosis were not found in the 10 patients without infection. CONCLUSION--Staining of tissue sections from paraffin wax embedded intestinal biopsy specimens with stains incorporating Uvitex 2B is a rapid and easy technique for the diagnosis of intestinal microsporidiosis. Images PMID:8543621

  14. Electronic structure study of TiB2 and Ti2B

    NASA Astrophysics Data System (ADS)

    Vashistha, M.; Kabra, K.; Vyas, V.; Sharma, G.

    2015-06-01

    In this paper, the electronic properties of TiB2 and Ti2B are computed within the framework of Density Functional Theory (DFT) based on Linear Combination of Atomic Orbitals (LCAO) method. In the present calculations, the generalized gradient approximation (GGA) proposed by Perdew-Burke-Erenzerhof (PBE) and Becke's scheme are considered to treat the correlation and exchange effects respectively. TiB2 crystallizes in the hexagonal AlB2 type structure which is designated as C32 with the space group P6/mmm. While the crystal structure of Ti2B described in this paper is isomorphous to the body centered tetragonal (Al2Cu - type) structure with space group I4/mcm.

  15. Raman Scattering Study of Superionic Conductor Lithium Tetraborate Li2B4O7

    NASA Astrophysics Data System (ADS)

    Dekola, Tatiana; Yagi, Toshirou; Taniguchi, Hiroki; Takesada, Masaki; Sekine, Ichiro

    2006-01-01

    Raman scattering spectra of the superionic-conductive lithium tetraborate Li2B4O7 are observed in the frequency range between 0-1600 cm-1 as a function of temperature from 4.2 K to room temperature. The frequencies of four Raman active A1(TO) modes of 262, 353, 378, and 423 cm-1 at 4.2 K are newly assigned to be related closely with the motion of the Li-ions in superionic conduction.

  16. A Phox2b BAC Transgenic Rat Line Useful for Understanding Respiratory Rhythm Generator Neural Circuitry

    PubMed Central

    Ikeda, Keiko; Takahashi, Masanori; Sato, Shigeru; Igarashi, Hiroyuki; Ishizuka, Toru; Yawo, Hiromu; Arata, Satoru; Southard-Smith, E. Michelle; Kawakami, Kiyoshi; Onimaru, Hiroshi

    2015-01-01

    The key role of the respiratory neural center is respiratory rhythm generation to maintain homeostasis through the control of arterial blood pCO2/pH and pO2 levels. The neuronal network responsible for respiratory rhythm generation in neonatal rat resides in the ventral side of the medulla and is composed of two groups; the parafacial respiratory group (pFRG) and the pre-Bötzinger complex group (preBötC). The pFRG partially overlaps in the retrotrapezoid nucleus (RTN), which was originally identified in adult cats and rats. Part of the pre-inspiratory (Pre-I) neurons in the RTN/pFRG serves as central chemoreceptor neurons and the CO2 sensitive Pre-I neurons express homeobox gene Phox2b. Phox2b encodes a transcription factor and is essential for the development of the sensory-motor visceral circuits. Mutations in human PHOX2B cause congenital hypoventilation syndrome, which is characterized by blunted ventilatory response to hypercapnia. Here we describe the generation of a novel transgenic (Tg) rat harboring fluorescently labeled Pre-I neurons in the RTN/pFRG. In addition, the Tg rat showed fluorescent signals in autonomic enteric neurons and carotid bodies. Because the Tg rat expresses inducible Cre recombinase in PHOX2B-positive cells during development, it is a potentially powerful tool for dissecting the entire picture of the respiratory neural network during development and for identifying the CO2/O2 sensor molecules in the adult central and peripheral nervous systems. PMID:26147470

  17. 12q24 locus association with type 1 diabetes: SH2B3 or ATXN2?

    PubMed Central

    Auburger, Georg; Gispert, Suzana; Lahut, Suna; Ömür, Özgür; Damrath, Ewa; Heck, Melanie; Başak, Nazlı

    2014-01-01

    Genetic linkage analyses, genome-wide association studies of single nucleotide polymorphisms, copy number variation surveys, and mutation screenings found the human chromosomal 12q24 locus, with the genes SH2B3 and ATXN2 in its core, to be associated with an exceptionally wide spectrum of disease susceptibilities. Hematopoietic traits of red and white blood cells (like erythrocytosis and myeloproliferative disease), autoimmune disorders (like type 1 diabetes, coeliac disease, juvenile idiopathic arthritis, rheumatoid arthritis, thrombotic antiphospholipid syndrome, lupus erythematosus, multiple sclerosis, hypothyroidism and vitiligo), also vascular pathology (like kidney glomerular filtration rate deficits, serum urate levels, plasma beta-2-microglobulin levels, retinal microcirculation problems, diastolic and systolic blood pressure and hypertension, cardiovascular infarction), furthermore obesity, neurodegenerative conditions (like the polyglutamine-expansion disorder spinocerebellar ataxia type 2, Parkinson’s disease, the motor-neuron disease amyotrophic lateral sclerosis, and progressive supranuclear palsy), and finally longevity were reported. Now it is important to clarify, in which ways the loss or gain of function of the locally encoded proteins SH2B3/LNK and ataxin-2, respectively, contribute to these polygenic health problems. SH2B3/LNK is known to repress the JAK2/ABL1 dependent proliferation of white blood cells. Its null mutations in human and mouse are triggers of autoimmune traits and leukemia (acute lymphoblastic leukemia or chronic myeloid leukemia-like), while missense mutations were found in erythrocytosis-1 patients. Ataxin-2 is known to act on RNA-processing and trophic receptor internalization. While its polyglutamine-expansion mediated gain-of-function causes neuronal atrophy in human and mouse, its deletion leads to obesity and insulin resistance in mice. Thus, it is conceivable that the polygenic pathogenesis of type 1 diabetes is

  18. Benzimidazole-2-carboxamides as novel NR2B selective NMDA receptor antagonists.

    PubMed

    Borza, István; Kolok, Sándor; Gere, Anikó; Nagy, József; Fodor, László; Galgóczy, Kornél; Fetter, József; Bertha, Ferenc; Agai, Béla; Horváth, Csilla; Farkas, Sándor; Domány, György

    2006-09-01

    A novel series of benzimidazole-2-carboxamide derivatives was prepared and identified as NR2B selective NMDA receptor antagonists. The influence of some structural elements, like H-bond donor groups placed on the benzimidazole skeleton and the substitution pattern of the piperidine ring, on the biological activity was studied. Compound 6a showed excellent analgetic activity in the mouse formalin test following po administration. PMID:16782335

  19. Everolimus Stabilizes Podocyte Microtubules via Enhancing TUBB2B and DCDC2 Expression

    PubMed Central

    Jeruschke, Stefanie; Jeruschke, Kay; DiStasio, Andrew; Karaterzi, Sinem; Büscher, Anja K.; Nalbant, Perihan; Klein-Hitpass, Ludger; Hoyer, Peter F.; Weiss, Jürgen; Stottmann, Rolf W.; Weber, Stefanie

    2015-01-01

    Background Glomerular podocytes are highly differentiated cells that are key components of the kidney filtration units. The podocyte cytoskeleton builds the basis for the dynamic podocyte cytoarchitecture and plays a central role for proper podocyte function. Recent studies implicate that immunosuppressive agents including the mTOR-inhibitor everolimus have a protective role directly on the stability of the podocyte actin cytoskeleton. In contrast, a potential stabilization of microtubules by everolimus has not been studied so far. Methods To elucidate mechanisms underlying mTOR-inhibitor mediated cytoskeletal rearrangements, we carried out microarray gene expression studies to identify target genes and corresponding pathways in response to everolimus. We analyzed the effect of everolimus in a puromycin aminonucleoside experimental in vitro model of podocyte injury. Results Upon treatment with puromycin aminonucleoside, microarray analysis revealed gene clusters involved in cytoskeletal reorganization, cell adhesion, migration and extracellular matrix composition to be affected. Everolimus was capable of protecting podocytes from injury, both on transcriptional and protein level. Rescued genes included tubulin beta 2B class IIb (TUBB2B) and doublecortin domain containing 2 (DCDC2), both involved in microtubule structure formation in neuronal cells but not identified in podocytes so far. Validating gene expression data, Western-blot analysis in cultured podocytes demonstrated an increase of TUBB2B and DCDC2 protein after everolimus treatment, and immunohistochemistry in healthy control kidneys confirmed a podocyte-specific expression. Interestingly, Tubb2bbrdp/brdp mice revealed a delay in glomerular podocyte development as showed by podocyte-specific markers Wilm’s tumour 1, Podocin, Nephrin and Synaptopodin. Conclusions Taken together, our study suggests that off-target, non-immune mediated effects of the mTOR-inhibitor everolimus on the podocyte cytoskeleton

  20. The α2B adrenergic receptor is mutant in cortical myoclonus and epilepsy

    PubMed Central

    De Fusco, Maurizio; Vago, Riccardo; Striano, Pasquale; Di Bonaventura, Carlo; Zara, Federico; Mei, Davide; Kim, Min Seuk; Muallem, Shmuel; Chen, Yunjia; Wang, Qin; Guerrini, Renzo; Casari, Giorgio

    2013-01-01

    Objective Autosomal dominant cortical myoclonus and epilepsy (ADCME) is characterized by distal, fairly rhythmic myoclonus and epilepsy with variable severity. We have previously mapped the disease locus on chromosome 2p11.1-q12.2 by genome-wide linkage analysis. Additional pedigrees affected by similar forms of epilepsy have been associated to chromosome 8q, 5p and 3q, but none of the causing genes has been identified. We aim at identifying the mutant gene responsible for this epileptic form. Methods Genes included in the ADCME critical region were prioritized and directly sequenced. Co-immunoprecipitation, immunofluorescence and electrophysiology approaches on transfected human cells have been utilized for testing the functional significance of the identified mutation. Results Here we show that mutation in the α2-adrenergic receptor subtype B (α2B-AR) associates to ADCME by identifying a novel in-frame insertion/deletion in two Italian families. The mutation alters several conserved residues of the third intracellular (3i) loop, neither hampering the α2B-AR plasma membrane localization nor the arrestin-mediated internalization capacity, but altering the binding with the scaffolding protein spinophilin upon neurotransmitter activation. Spinophilin, in turn, regulates interaction of GPCRs with Regulators of G proteins Signaling proteins. Accordingly, the mutant α2B-AR increases the epinephrine-stimulated calcium signaling. Interpretation The identified mutation is responsible for ADCME, as the loss of α2B-AR/spinophilin interaction causes a gain of function effect. This work implicates for the first time the α-adrenergic system in human epilepsy and opens new ways for understanding the molecular pathway of epileptogenesis, widening the spectrum of possible therapeutic targets. PMID:24114805

  1. Influence of Surface Preparation for Different Groups of A2B6 Mixed Crystals

    NASA Astrophysics Data System (ADS)

    Zakrzewski, J.; Maliński, M.; Strzałkowski, K.; Firszt, F.; Łęgowski, S.; Męczyńska, H.

    2010-01-01

    Piezoelectric photothermal spectroscopy has been used for measurements of the optical and thermal parameters of semiconductors. The investigated crystals were grown by the high-pressure Bridgman method under argon overpressure. The obtained photoacoustic (PA) spectra show the complexity of the effects observed for the different groups of selected A2B6 crystals. These effects comprise ideal samples and samples with damaged surfaces. The spectra show the influence of the surface treatment on the PA amplitude and phase spectra.

  2. Electrochemistry of mammalian cytochrome P450 2B4 indicates tunable thermodynamic parameters in surfactant films.

    PubMed

    Hagen, Katharine D; Gillan, James M; Im, Sang-Choul; Landefeld, Sally; Mead, Griffin; Hiley, Megan; Waskell, Lucy A; Hill, Michael G; Udit, Andrew K

    2013-12-01

    Electrochemical methods continue to present an attractive means for achieving in vitro biocatalysis with cytochromes P450; however understanding fully the nature of electrode-bound P450 remains elusive. Herein we report thermodynamic parameters using electrochemical analysis of full-length mammalian microsomal cytochrome P450 2B4 (CYP 2B4) in didodecyldimethylammonium bromide (DDAB) surfactant films. Electronic absorption spectra of CYP 2B4-DDAB films on silica slides reveal an absorption maximum at 418nm, characteristic of low-spin, six-coordinate, water-ligated Fe(III) heme in P450. The Fe(III/II) and Fe(II/I) redox couples (E1/2) of substrate-free CYP 2B4 measured by cyclic voltammetry are -0.23V and -1.02V (vs. SCE, or 14mV and -776mV vs. NHE) at 21°C. The standard heterogeneous rate constant for electron transfer from the electrode to the heme for the Fe(III/II) couple was estimated at 170s(-1). Experiments indicate that the system is capable of catalytic reduction of dioxygen, however substrate oxidation was not observed. From the variation of E1/2 with temperature (18-40°C), we have measured entropy and enthalpy changes that accompany heme reduction, -151Jmol(-1)K(-1) and -46kJmol(-1), respectfully. The corresponding entropy and enthalpy values are less for the six-coordinate low-spin, imidazole-ligated enzyme (-59Jmol(-1)K(-1) and -18kJmol(-1)), consistent with limited conformational changes upon reduction. These thermodynamic parameters are comparable to those measured for bacterial P450 from Bacillus megaterium (CYP BM3), confirming our prior reports that the surfactant environment exerts a strong influence on the redox properties of the heme. PMID:24013063

  3. Fluoxetine and all other SSRIs are 5-HT2B Agonists - Importance for their Therapeutic Effects

    PubMed Central

    Peng, Liang; Gu, Li; Li, Baoman; Hertz, Leif

    2014-01-01

    Fluoxetine and other serotonin-specific re-uptake inhibitors (SSRIs) are generally thought to owe their therapeutic potency to inhibition of the serotonin transporter (SERT). However, research in our laboratory showed that it affects, with relatively high affinity the 5-HT2B receptor in cultured astrocytes; this finding was confirmed by independent observations showing that fluoxetine loses its ability to elicit SSRI-like responses in behavioral assays in mice in which the 5-HT2B receptor was knocked-out genetically or inhibited pharmacologically. All clinically used SSRIs are approximately equipotent towards 5-HT2B receptors and exert their effect on cultured astrocytes at concentrations similar to those used clinically, a substantial difference from their effect on SERT. We have demonstrated up-regulation and editing of astrocytic genes for ADAR2, the kainate receptor GluK2, cPLA2 and the 5-HT2B receptor itself after chronic treatment of cultures, which do not express SERT and after treatment of mice (expressing SERT) for 2 weeks with fluoxetine, followed by isolation of astrocytic and neuronal cell fractionation. Affected genes were identical in both experimental paradigms. Fluoxetine treatment also altered Ca2+ homeostatic cascades, in a specific way that differs from that seen after treatment with the anti-bipolar drugs carbamazepine, lithium, or valproic acid. All changes occurred after a lag period similar to what is seen for fluoxetine’s clinical effects, and some of the genes were altered in the opposite direction by mild chronic inescapable stress, known to cause anhedonia, a component of major depression. In the anhedonic mice these changes were reversed by treatment with SSRIs. PMID:25342944

  4. Technical description of space ultra reliable modular computer (SUMC), model 2 B

    NASA Technical Reports Server (NTRS)

    1975-01-01

    The design features of the SUMC-2B computer, also called the IBM-HTC are described. It is general purpose digital computer implemented with flexible hardware elements and microprograming to enable low cost customizing to a wide range of applications. It executes the S/360 standard instruction set to maintain problem state compability. Memory technology, extended instruction sets, and I/O channel variations are among the available options.

  5. Complete Genome Sequence of Porcine Circovirus 2b Strain CC1

    PubMed Central

    Yang, Xin; Chen, Fuwang; Cao, Yuhang; Pang, Daxing

    2012-01-01

    A porcine circovirus 2 (PCV2) strain, designated CC1, was isolated and purified from tissue samples from pigs with wasting syndromes in China. We report the complete genome sequence of PCV2b strain CC1 with a deletion of C at position 1053 resulting in elongation of open reading frame 2 (ORF2) and formation of ORF5. There were 11 ORFs in the genome. PMID:22879609

  6. Allosteric modulators of NR2B-containing NMDA receptors: molecular mechanisms and therapeutic potential.

    PubMed

    Mony, Laetitia; Kew, James N C; Gunthorpe, Martin J; Paoletti, Pierre

    2009-08-01

    N-methyl-D-aspartate receptors (NMDARs) are ion channels gated by glutamate, the major excitatory neurotransmitter in the mammalian central nervous system (CNS). They are widespread in the CNS and are involved in numerous physiological and pathological processes including synaptic plasticity, chronic pain and psychosis. Aberrant NMDAR activity also plays an important role in the neuronal loss associated with ischaemic insults and major degenerative disorders including Parkinson's and Alzheimer's disease. Agents that target and alter NMDAR function may, thus, have therapeutic benefit. Interestingly, NMDARs are endowed with multiple extracellular regulatory sites that recognize ions or small molecule ligands, some of which are likely to regulate receptor function in vivo. These allosteric sites, which differ from agonist-binding and channel-permeation sites, provide means to modulate, either positively or negatively, NMDAR activity. The present review focuses on allosteric modulation of NMDARs containing the NR2B subunit. Indeed, the NR2B subunit confers a particularly rich pharmacology with distinct recognition sites for exogenous and endogenous allosteric ligands. Moreover, NR2B-containing receptors, compared with other NMDAR subtypes, appear to contribute preferentially to pathological processes linked to overexcitation of glutamatergic pathways. The actions of extracellular H+, Mg2+, Zn2+, of polyamines and neurosteroids, and of the synthetic compounds ifenprodil and derivatives ('prodils') are presented. Particular emphasis is put upon the structural determinants and molecular mechanisms that underlie the effects exerted by these agents. A better understanding of how NR2B-containing NMDARs (and NMDARs in general) operate and how they can be modulated should help define new strategies to counteract the deleterious effects of dysregulated NMDAR activity. PMID:19594762

  7. Herstellung von Chitosan und einige Anwendungen

    NASA Astrophysics Data System (ADS)

    Struszczyk, Marcin Henryk

    2001-05-01

    1. Die Deacetylierung von crabshell - Chitosan führte gleichzeitig zu einem drastischen Abfall der mittleren viscosimetrischen Molmasse ( Mv), insbesondere wenn die Temperatur und die Konzentration an NaOH erhöht werden. Diese Parameter beeinflussten jedoch nicht den Grad der Deacetylierung (DD). Wichtig ist jedoch die Quelle des Ausgangsmaterials: Chitin aus Pandalus borealis ist ein guter Rohstoff für die Herstellung von Chitosan mit niedrigem DD und gleichzeitig hoher mittlerer Mv, während Krill-Chitin (Euphausia superba) ein gutes Ausgangsmaterial zur Herstellung von Chitosan mit hohem DD und niedrigem Mv ist. Chitosan, das aus Insekten (Calliphora erythrocephala), unter milden Bedingungen (Temperatur: 100°C, NaOH-Konzentration: 40 %, Zeit: 1-2h ) hergestellt wurde, hatte die gleichen Eigenschaften hinsichtlich DD und Mv wie das aus Krill hergestellte Chitosan. Der Bedarf an Zeit, Energie und NaOH ist für die Herstellung von Insekten-Chitosan geringer als für crabshell-Chitosan vergleichbare Resultaten für DD und Mv. 2. Chitosan wurde durch den Schimmelpilz Aspergillus fumigatus zu Chitooligomeren fermentiert. Die Ausbeute beträgt 25%. Die Chitooligomere wurden mit Hilfe von HPLC und MALDI-TOF-Massenspektrmetrie identifiziert. Die Fermentationsmischung fördert die Immunität von Pflanzen gegen Bakterien und Virusinfektion. Die Zunahme der Immunität schwankt jedoch je nach System Pflanze-Pathogen. Die Fermentation von Chitosan durch Aspergillus fumigatus könnte eine schnelle und billige Methode zur Herstellung von Chitooligomeren mit guter Reinheit und Ausbeute sein. Eine partiell aufgereinigte Fermentationsmischung dieser Art könnte in der Landwirtschaft als Pathogeninhibitor genutzt werden. Durch kontrollierte Fermentation, die Chitooligomere in definierter Zusammensetzung (d.h. definierter Verteilung des Depolymerisationsgrades) liefert, könnte man zu Mischungen kommen, die für die jeweilige Anwendung eine optimale Bioaktivität besitzen. 3

  8. Hydroxysteroid Sulfotransferase SULT2B1b Promotes Hepatocellular Carcinoma Cells Proliferation In Vitro and In Vivo

    PubMed Central

    Yang, Xiaoming; Xu, Yali; Guo, Fenghua; Ning, Yanxia; Zhi, Xiuling; Yin, Lianhua; Li, Xiaobo

    2013-01-01

    Hydroxysteroid sulfotransferase 2B1b (SULT2B1b) is highly selective for the addition of sulfate groups to 3β-hydroxysteroids. Although previous reports have suggested that SULT2B1b is correlated with cell proliferation of hepatocytes, the relationship between SULT2B1b and the malignant phenotype of hepatocarcinoma cells was not clear. In the present study, we found that SULT2B1 was comparatively higher in the human hepatocarcinoma tumorous tissues than their adjacent tissues. Besides, SULT2B1b overexpression promoted the growth of the mouse hepatocarcinoma cell line Hepa1-6, while Lentivirus-mediated SULT2B1b interference inhibited growth as assessed by the CCK-8 assay. Likewise, inhibition of SULT2B1b expression induced cell-cycle arrest and apoptosis in Hepa1-6 cells by upregulating the expression of FAS, downregulating the expression of cyclinB1, BCL2 and MYC in vitro and in vivo at both the transcript and protein levels. Knock-down of SULT2B1b expression significantly suppressed tumor growth in nude mouse xenografts. Moreover, proliferation rates and SULT2B1b expression were highly correlated in the human hepatocarcinoma cell lines Huh-7, Hep3B, SMMC-7721 and BEL-7402 cells. Knock-down of SULT2B1b inhibited cell growth and cyclinB1 levels in human hepatocarcinoma cells and suppressed xenograft growth in vivo. In conclusion, SULT2B1b expression promotes proliferation of hepatocellular carcinoma cells in vitro and in vivo, which may contribute to the progression of HCC. PMID:23593328

  9. Histone demethylase JMJD2B is required for tumor cell proliferation and survival and is overexpressed in gastric cancer

    SciTech Connect

    Li, Wenjuan; Zhao, Li; Zang, Wen; Liu, Zhifang; Chen, Long; Liu, Tiantian; Jia, Jihui

    2011-12-16

    Highlights: Black-Right-Pointing-Pointer JMJD2B is required for cell proliferation and in vivo tumorigenesis. Black-Right-Pointing-Pointer JMJD2B depletion induces apoptosis and/or cell cycle arrest. Black-Right-Pointing-Pointer JMJD2B depletion activates DNA damage response and enhances p53 stabilization. Black-Right-Pointing-Pointer JMJD2B is overexpressed in human primary gastric cancer. -- Abstract: Epigenetic alterations such as aberrant expression of histone-modifying enzymes have been implicated in tumorigenesis. Jumonji domain containing 2B (JMJD2B) is a newly identified histone demethylase that regulates chromatin structure or gene expression by removing methyl residues from trimethylated lysine 9 on histone H3. Recent observations have shown oncogenic activity of JMJD2B. We explored the functional role of JMJD2B in cancer cell proliferation, survival and tumorigenesis, and determined its expression profile in gastric cancer. Knocking down JMJD2B expression by small interfering RNA (siRNA) in gastric and other cancer cells inhibited cell proliferation and/or induced apoptosis and elevated the expression of p53 and p21{sup CIP1} proteins. The enhanced p53 expression resulted from activation of the DNA damage response pathway. JMJD2B knockdown markedly suppressed xenograft tumor growth in vivo in mice. Moreover, JMJD2B expression was increased in primary gastric-cancer tissues of humans. Thus, JMJD2B is required for sustained proliferation and survival of tumor cells in vitro and in vivo, and its aberrant expression may contribute to the pathogenesis of gastric cancer.

  10. CDKN2B expression and subcutaneous adipose tissue expandability: Possible influence of the 9p21 atherosclerosis locus

    SciTech Connect

    Svensson, Per-Arne; Wahlstrand, Björn; Olsson, Maja; Froguel, Philippe; Falchi, Mario; Bergman, Richard N.; McTernan, Philip G.; Hedner, Thomas; Carlsson, Lena M.S.; Jacobson, Peter

    2014-04-18

    Highlights: • The tumor suppressor gene CDKN2B is highly expressed in human adipose tissue. • Risk alleles at the 9p21 locus modify CDKN2B expression in a BMI-dependent fashion. • There is an inverse relationship between expression of CDKN2B and adipogenic genes. • CDKN2B expression influences to postprandial triacylglycerol clearance. • CDKN2B expression in adipose tissue is linked to markers of hepatic steatosis. - Abstract: Risk alleles within a gene desert at the 9p21 locus constitute the most prevalent genetic determinant of cardiovascular disease. Previous research has demonstrated that 9p21 risk variants influence gene expression in vascular tissues, yet the biological mechanisms by which this would mediate atherosclerosis merits further investigation. To investigate possible influences of this locus on other tissues, we explored expression patterns of 9p21-regulated genes in a panel of multiple human tissues and found that the tumor suppressor CDKN2B was highly expressed in subcutaneous adipose tissue (SAT). CDKN2B expression was regulated by obesity status, and this effect was stronger in carriers of 9p21 risk alleles. Covariation between expression of CDKN2B and genes implemented in adipogenesis was consistent with an inhibitory effect of CDKN2B on SAT proliferation. Moreover, studies of postprandial triacylglycerol clearance indicated that CDKN2B is involved in down-regulation of SAT fatty acid trafficking. CDKN2B expression in SAT correlated with indicators of ectopic fat accumulation, including markers of hepatic steatosis. Among genes regulated by 9p21 risk variants, CDKN2B appears to play a significant role in the regulation of SAT expandability, which is a strong determinant of lipotoxicity and therefore might contribute to the development of atherosclerosis.

  11. 3 CFR - Presidential Determination for the Lao People's Democratic Republic Under Section 2(b)(2) of the...

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... Democratic Republic Under Section 2(b)(2) of the Export-Import Bank Act of 1945, as amended Presidential... Determination for the Lao People's Democratic Republic Under Section 2(b)(2) of the Export-Import Bank Act of... section 2(b)(C) of the Export-Import Bank Act of 1945, as amended (12 U.S.C. 635(b)(2)(C)), I...

  12. Structural and biochemical analyses of monoubiquitinated human histones H2B and H4

    PubMed Central

    Machida, Shinichi; Sekine, Satoshi; Nishiyama, Yuuki; Horikoshi, Naoki; Kurumizaka, Hitoshi

    2016-01-01

    Monoubiquitination is a major histone post-translational modification. In humans, the histone H2B K120 and histone H4 K31 residues are monoubiquitinated and may form transcriptionally active chromatin. In this study, we reconstituted nucleosomes containing H2B monoubiquitinated at position 120 (H2Bub120) and/or H4 monoubiquitinated at position 31 (H4ub31). We found that the H2Bub120 and H4ub31 monoubiquitinations differently affect nucleosome stability: the H2Bub120 monoubiquitination enhances the H2A–H2B association with the nucleosome, while the H4ub31 monoubiquitination decreases the H3–H4 stability in the nucleosome, when compared with the unmodified nucleosome. The H2Bub120 and H4ub31 monoubiquitinations both antagonize the Mg2+-dependent compaction of a poly-nucleosome, suggesting that these monoubiquitinations maintain more relaxed conformations of chromatin. In the crystal structure, the H2Bub120 and H4ub31 monoubiquitinations do not change the structure of the nucleosome core particle and the ubiquitin molecules were flexibly disordered in the H2Bub120/H4ub31 nucleosome structure. These results revealed the differences and similarities of the H2Bub120 and H4ub31 monoubiquitinations at the mono- and poly-nucleosome levels and provide novel information to clarify the roles of monoubiquitination in chromatin. PMID:27335322

  13. A study of single nucleotide polymorphisms of GRIN2B in schizophrenia from Chinese Han population.

    PubMed

    Guo, Zhenming; Niu, Weibo; Bi, Yan; Zhang, Rui; Ren, Decheng; Hu, Jiaxin; Huang, Xiaoye; Wu, Xi; Cao, Yanfei; Yang, Fengping; Wang, Lu; Li, Weidong; Li, Xingwang; Xu, Yifeng; He, Lin; Yu, Tao; He, Guang

    2016-09-01

    Schizophrenia is a severe and complex mental disorder with high heritability. There is evidence that mutations in the gene of Nmethyl-d-aspartate-type glutamate receptors (NMDAR) are associated with schizophrenia. GRIN2B encodes a subunit of NMDARs, and has been identified as a candidate gene for many psychiatric disorders, especially schizophrenia. In this study, we investigated whether single nucleotide polymorphisms (SNPs) in GRIN2B were associated with schizophrenia. Four SNPs (rs890, rs1806191, rs219872, rs172677) were genotyped in 752 schizophrenic patients and 846 healthy controls of the Chinese Han population. Our results indicate differences in allele and genotype frequencies of rs890 between case and control. These results were assessed by adapting different genetic models (codominant, dominant, recessive, overdominant, log-additive models). After controlling for confounding factors including sex and age, rs890 remained associated with schizophrenia. In addition, rs890 and rs1806191 were found to form a haplotype associated with schizophrenia. In summary, our results indicate that the GRIN2B SNP rs890 might be associated with schizophrenia in the Chinese Han population. PMID:27453061

  14. The behaviors of anatase and TiO2(B) phase coexisting nanosheets under high pressure

    NASA Astrophysics Data System (ADS)

    Huang, Yanwei; Li, Wentao; Ren, Xiangting; Yu, Zhenhai; Samanta, Sudeshna; Yan, Shuai; Zhang, Jun; Wang, Lin

    2016-03-01

    High pressure behaviors of anatase TiO2 and TiO2(B) coexisting nanosheets were investigated using in situ synchrotron X-ray diffraction and Raman Spectroscopy. The X-ray diffraction revealed that upon compression an α-PbO2 phase appeared at 11.4 GPa, and then the baddeleyite phase appeared at 23.6 GPa. Upon decompression the anatase phase still existed obviously and TiO2(B) phase almost cannot be observed. The Raman spectrum at ambient pressure presented the typical curve of anatase TiO2, however the pressure dependence for compression and decompression did not show the common phase transion from anatase to α-PbO2 or to baddeleyite. This is different from high pressure behaviors of other TiO2 nanostructures and could be attributed to the existence of small amount of TiO2(B) at the starting materials. The pressure relationship of the Raman frequencies shift slope indicated the coexistence nanosheet has high incompressibility compared with other TiO2 nanomaterials and corresponding bulks.

  15. A Novel Role of Serotonin Receptor 2B Agonist as an Anti-Melanogenesis Agent

    PubMed Central

    Oh, Eun Ju; Park, Jong Il; Lee, Ji Eun; Myung, Cheol Hwan; Kim, Su Yeon; Chang, Sung Eun; Hwang, Jae Sung

    2016-01-01

    BW723C86, a serotonin receptor 2B agonist, has been investigated as a potential therapeutic for various conditions such as anxiety, hyperphagia and hypertension. However, the functional role of BW723C86 against melanogenesis remains unclear. In this study, we investigate the effect of serotonin receptor 2B (5-HTR2B) agonist on melanogenesis and elucidate the mechanism involved. BW723C86 reduced melanin synthesis and intracellular tyrosinase activity in melan-A cells and normal human melanocytes. The expression of melanogenesis-related proteins (tyrosinase, TRP-1 and TRP-2) and microphthalmia-associated transcription factor (MITF) in melan-A cells decreased after BW723C86 treatment. The promoter activity of MITF was also reduced by BW723C86 treatment. The reduced level of MITF was associated with inhibition of protein kinase A (PKA) and cAMP response element-binding protein (CREB) activation by BW723C86 treatment. These results suggest that the serotonin agonist BW723C86 could be a potential therapeutic agent for skin hyperpigmentation disorders. PMID:27077852

  16. Employing complex polyhierarchical ontologies and promoting interoperability of i2b2 data systems.

    PubMed

    Campbell, James Richard; Campbell, Walter Scott; Hickman, Hubert; Pedersen, Jay; McClay, James

    2015-01-01

    I2b2 is in widespread use for managing research data warehouses. It employs reference ontologies as a record index and supports searching for aggregate cases using a pattern match operator on ASCII strings representing the node traversal from root to concept(PATHs). This creates complexities in dissemination and deployment for large polyhierarchical ontologies such as SNOMED CT. We hypothesized that an alternative approach employing transitive closure tables (TC) could lead to more accurate, efficient and interoperable search tools for i2b2. We evaluated search speed, accuracy and interoperability of queries employing each approach. We found both TC-based and PATH-based queries to produce accurate results. However, we observed that TC-based queries involving concepts included in large numbers of paths ran substantially faster than PATH-based queries for the same concept. Oracle query plan resource estimates differed by one to three orders of magnitude for these queries. We conclude that a simplification of dissemination tools for SNOMED CT and revision in the metadata build for i2b2 can effectively employ SNOMED CT with increased efficiency and comparable accuracy. Use of transitive closure tables in metadata can promote network query interoperability. PMID:26958167

  17. CRL4Wdr70 regulates H2B monoubiquitination and facilitates Exo1-dependent resection

    PubMed Central

    Zeng, Ming; Ren, Laifeng; Mizuno, Ken'Ichi; Nestoras, Konstantinos; Wang, Haibin; Tang, Zizhi; Guo, Liandi; Kong, Daochun; Hu, Qiwen; He, Qun; Du, Lilin; Carr, Antony M.; Liu, Cong

    2016-01-01

    Double-strand breaks repaired by homologous recombination (HR) are first resected to form single-stranded DNA, which binds replication protein A (RPA). RPA attracts mediators that load the Rad51 filament to promote strand invasion, the defining feature of HR. How the resection machinery navigates nucleosome-packaged DNA is poorly understood. Here we report that in Schizosaccharomyces pombe a conserved DDB1-CUL4-associated factor (DCAF), Wdr70, is recruited to DSBs as part of the Cullin4-DDB1 ubiquitin ligase (CRL4Wdr70) and stimulates distal H2B lysine 119 mono-ubiquitination (uH2B). Wdr70 deletion, or uH2B loss, results in increased loading of the checkpoint adaptor and resection inhibitor Crb253BP1, decreased Exo1 association and delayed resection. Wdr70 is dispensable for resection upon Crb253BP1 loss, or when the Set9 methyltransferase that creates docking sites for Crb2 is deleted. Finally, we establish that this histone regulatory cascade similarly controls DSB resection in human cells. PMID:27098497

  18. Behavioral phenotype in five individuals with de novo mutations within the GRIN2B gene

    PubMed Central

    2013-01-01

    Background Intellectual disability (ID) is often associated with behavioral problems or disorders. Mutations in the GRIN2B gene (MRD6, MIM613970) have been identified as a common cause of ID (prevalence of 0.5 – 1% in individuals with ID) associated with EEG and behavioral problems. Methods We assessed five GRIN2B mutation carriers aged between 3 and 14 years clinically and via standardized questionnaires to delineate a detailed behavioral phenotype. Parents and teachers rated problem behavior of their affected children by completing the Developmental Behavior Checklist (DBC) and the Conners’ Rating Scales Revised (CRS-R:L). Results All individuals had mild to severe ID and needed guidance in daily routine. They showed characteristic behavior problems with prominent hyperactivity, impulsivity, distractibility and a short attention span. Stereotypies, sleeping problems and a friendly but boundless social behavior were commonly reported. Conclusion Our observations provide an initial delineation of the behavioral phenotype of GRIN2B mutation carriers. PMID:23718928

  19. Theoretical structures and experimental vibrational spectra of isomeric benzofused thieno [3,2- b] furan compounds

    NASA Astrophysics Data System (ADS)

    Ledesma, A. E.; Contreras, C.; Svoboda, J.; Vektariane, A.; Brandán, S. A.

    2010-04-01

    A theoretical structural and experimental vibrational study for the benzothieno [3,2- b] furan and thieno [3,2- b] benzofuran compounds is presented. The density functional theory (DFT) has been used to study its structures and vibrational properties. The geometries were fully optimised at the B3LYP/6-31G∗ and B3LYP/6-311++G∗∗ levels of theory and the harmonic vibrational frequencies were evaluated at the same levels. The calculated harmonic vibrational frequencies for the compound are consistent with the experimental IR spectrum in chloroform solution. These calculations gave us precise knowledge of the normal modes of vibration of these compounds. A complete assignment of all the observed bands in the infrared and Raman spectra for both benzothieno [3,2- b] furans compound was performed. The nature of the different rings bonds in both compounds was quantitatively investigated by means of Natural Bond Orbital (NBO) analysis. The topological properties of electronic charge density are analysed by employing Bader's Atoms in the Molecules theory (AIM).

  20. A new phosphor Li2B4O7: Cu for TLD.

    PubMed

    Takenaga, M; Yamamoto, O; Yamashita, T

    1983-04-01

    The phosphor Li2B4O7: Cu (0.03% by weight) has an effective atomic number of 7.3, which is very similar to that of tissue (7.4). This suggests that the phosphor should have excellent properties for thermoluminescent dosimetry. The phosphor prepared by a sintering method shows two glow peaks composed of a dosimetric peak at 205 degrees C and a shoulder at 120 degrees C, and a broad emission band peaking at 368 nm. The material based on the stoichiometric compound of Li2O . 2B2O3 has a good moisture resistant property. The dosimetric characteristics are as follows: (1) The sensitivity of gamma rays is about 20 times higher than that of Li2B4O2: Mn prepared by the conventional melting method. (2) The dosimetry peak of 205 degrees C fades less than 9% in intensity at 25 degrees C after 60 days in dark. (3) The TL output is linear with exposure to about 10(5) R, becoming sublinear above it. (4) The sensitivity loss caused by humidity is about 10-25% after 2-6 months of storage in air of 90% relative humidity at 25 degrees C. (5) The energy dependence of TL output for photons is flat within the limit of 10% from 40 keV to 7 MeV. (6) The light induced fading is 10% after 3 h room lighting at 1000 lux. PMID:6841096

  1. A Novel Role of Serotonin Receptor 2B Agonist as an Anti-Melanogenesis Agent.

    PubMed

    Oh, Eun Ju; Park, Jong Il; Lee, Ji Eun; Myung, Cheol Hwan; Kim, Su Yeon; Chang, Sung Eun; Hwang, Jae Sung

    2016-01-01

    BW723C86, a serotonin receptor 2B agonist, has been investigated as a potential therapeutic for various conditions such as anxiety, hyperphagia and hypertension. However, the functional role of BW723C86 against melanogenesis remains unclear. In this study, we investigate the effect of serotonin receptor 2B (5-HTR2B) agonist on melanogenesis and elucidate the mechanism involved. BW723C86 reduced melanin synthesis and intracellular tyrosinase activity in melan-A cells and normal human melanocytes. The expression of melanogenesis-related proteins (tyrosinase, TRP-1 and TRP-2) and microphthalmia-associated transcription factor (MITF) in melan-A cells decreased after BW723C86 treatment. The promoter activity of MITF was also reduced by BW723C86 treatment. The reduced level of MITF was associated with inhibition of protein kinase A (PKA) and cAMP response element-binding protein (CREB) activation by BW723C86 treatment. These results suggest that the serotonin agonist BW723C86 could be a potential therapeutic agent for skin hyperpigmentation disorders. PMID:27077852

  2. Imported Genotype 2B Rubella Virus Caused the 2012 Outbreak in Anqing City, China

    PubMed Central

    Dai, Jingjing; Chen, Xia; Tang, Jihai; Chen, Shuping; Zheng, Yilun; Song, Jie; Xu, Wenbo

    2015-01-01

    A rubella outbreak occurred in Anqing city of Anhui province, China, from February to July of 2012, and a total of 241 clinically diagnosed or lab-confirmed patients were reported. The highest number of rubella cases during this outbreak was recorded in teenagers between 10 and 19 years of age who had not previously received the rubella vaccine. Genotyping results indicated that the genotype 2B rubella virus (RV) was responsible for the outbreak. However, a phylogenetic analysis showed that the genotype 2B RVs isolated in Anqing City were not related to 2B RVs found in other cities of Anhui province and in other provinces of China, thus providing evidence for importation. After importation, the transmission of Anqing RVs was interrupted owing to an effective immunization campaign against rubella, suggesting the timeliness and effectiveness of contingency vaccination. Strengthening rubella surveillance, including the integration of epidemiologic information and laboratory data, is a vital strategy for rubella control and elimination. In addition, except for routine immunization, targeted supplementary immunization activities aimed at susceptible groups according to sero-epidemiological surveillance data also play a key role in stopping the continuous transmission of rubella viruses and in preventing further congenital rubella syndrome cases. PMID:26402467

  3. Interstitial pneumonitis associated with pegylated interferon alpha-2b therapy for chronic hepatitis C: case report.

    PubMed

    Carrillo-Esper, Raúl; González-Avila, Daniela; Uribe-Ríos, Marittza; Méndez-Sánchez, Nahum

    2008-01-01

    Since 2004, pegylated interferon (P-IFN) in combination with ribavirin has become the optimal choice of therapy for chronic hepatitis C virus (HCV) infection. IFN a-2b suppresses HCV replication and restores elevated serum aminotransferase levels, leading to improvements in the histological changes in the livers of patients with chronic hepatitis C. Unfortunately, P-IFN has several adverse effects, including pneumonitis. This complication has been reported in the treatment of malignant diseases and CHC. We report a patient with interstitial pneumonitis thought to be caused by an IFN-based treatment in an unusual scenario of a patient with HCV-related Child-Pugh stage A cirrhosis, who experienced dyspnea, fever, and cough after 12 months of treatment with P-IFN a-2b. Her lung injury and pulmonary symptoms did not disappear despite discontinuation of IFN and the administration of corticosteroid. We concluded that the patient developed a fatal interstitial pneumonitis associated with P-INF a-2b therapy. PMID:18376374

  4. Interferon alpha 2b as maintenance therapy improves outcome in follicular lymphoma.

    PubMed

    Avilés, Agustin; Neri, Natividad; Huerta-Guzmán, Judith; Pérez, Felipe; Sotelo, León

    2004-11-01

    The role of interferon alpha as maintenance therapy in follicular lymphoma (FL) remains unsolved. We started a controlled clinical trial to assess if interferon alpha 2b could improve outcome, measured with event free survival (EFS) and overall survival (OS) in patients with FL in complete remission after chemotherapy based anthracyclines and adjuvant radiotherapy to sites of initial bulky disease. Three hundred and eighty four patients in complete response after 6 cycles of CEOP-Bleo (cyclophosphamide, epirubicin, vincristine, prednisone and bleomycin, at standard doses), and adjuvant radiotherapy when necessary, were randomized to received Interferon alpha 2b, three times a week for 1 year or no treatment (control group). Median follow up was 9.8 years (range 7.0-15 years); actuarial curves showed that EFS was 64% (95% confidence interval (CI) 56-71%) in patients treated with interferon that was statistically significant to patients in the control group: 35% (95% CI: 28-43%) (p<.01). OS was also statistically significant: 81% in patients treated with interferon (95% CI: 74-93%) and 57% (95% CI: 50-63%) in the control group (p<.001). Toxicity was mild, all patients received the planned dose of interferon on time. The use of aggressive chemotherapy and maintenance therapy with interferon alpha 2b in follicular lymphoma improved outcome; more than 60% of patients remain alive free of disease at longer follow-up. PMID:15512813

  5. Continuous infusion of 5-fluorouracil with alpha 2b interferon for advanced colorectal carcinoma.

    PubMed Central

    Ferguson, J. E.; Hulse, P.; Lorigan, P.; Jayson, G.; Scarffe, J. H.

    1995-01-01

    Thirty patients with symptomatic colorectal carcinoma were commenced on treatment with 5-fluorouracil (2.5 g week-1) administered by continuous intravenous infusion and alpha 2b interferon (3 x 10(6) U s.c. three times a week). Six out of 30 patients (20%) achieved a partial response. Three patients (10%) had stable disease and 21 patients (70%) progressed on treatment. Twenty patients (67%) completed ten or more weeks of treatment. In nine patients, treatment was withdrawn after 2-9 weeks because of disease progression or death. One patient's treatment was interrupted by emergency surgery. The median survival for all patients was 210 days (7 months). The principal side-effects were oral mucositis (12/30 patients), nausea (8/30 patients) and transient diarrhoea (4/30 patients), and initial constitutional symptoms due to alpha 2b interferon. The combination of low-dose continuous infusional 5-fluorouracil and low-dose alpha 2b interferon is well tolerated but has no obvious advantage over alternative infusional regimens using 5-fluorouracil as a single agent. PMID:7599051

  6. TRANSMISSION SPECTROSCOPY OF EXOPLANET XO-2b OBSERVED WITH HUBBLE SPACE TELESCOPE NICMOS

    SciTech Connect

    Crouzet, N.; McCullough, P. R.; Long, D.; Burke, C.

    2012-12-10

    Spectroscopy during planetary transits is a powerful tool to probe exoplanet atmospheres. We present the near-infrared transit spectroscopy of XO-2b obtained with Hubble Space Telescope NICMOS. Uniquely for NICMOS transit spectroscopy, a companion star of similar properties to XO-2 is present in the field of view. We derive improved star and planet parameters through a photometric white-light analysis. We show a clear correlation of the spectrum noise with instrumental parameters, in particular the angle of the spectral trace on the detector. An MCMC method using a decorrelation from instrumental parameters is used to extract the planetary spectrum. Spectra derived independently from each of the three visits have an rms of 430, 510, and 1000 ppm, respectively. The same analysis is performed on the companion star after numerical injection of a transit with a depth constant at all wavelengths. The extracted spectra exhibit residuals of similar amplitude as for XO-2, which represent the level of remaining NICMOS systematics. This shows that extracting planetary spectra is at the limit of NICMOS's capability. We derive a spectrum for the planet XO-2b using the companion star as a reference. The derived spectrum can be represented by a theoretical model including atmospheric water vapor or by a flat spectrum model. We derive a 3{sigma} upper limit of 1570 ppm on the presence of water vapor absorption in the atmosphere of XO-2b. In the Appendix, we perform a similar analysis for the gas giant planet XO-1b.

  7. What Caused the Lead burn-out in Spectrometer Magnet 2B

    SciTech Connect

    Green, Michael A

    2010-11-29

    The spectrometer solenoids are supposed to be the first magnets installed in the MICE Cooling Channel. The results of the test of Spectrometer Magnet 2B are reported in a previous MICE Note. Magnet 2B was tested with all five coils connected in series. The magnet failed because a lead to coil M2 failed before it could be trained to its full design current of 275 A. First, this report describes the condition of the magnet when the lead failure occurred. The lead that failed was between the cold mass feed-through and the heavy lead that connected to coil M2 and the quench protection diodes. It is believed that the lead failed because the minimum propagation zone (MPZ) length was too short. The quench was probably triggered by lead motion in the field external to the magnet center coil. The effect of heat transfer on quench propagation and MPZ length is discussed. The MPZ length is compared for a number of cases that apply to the spectrometer solenoid 2B as built and as it has been repaired. The required heat transfer coefficient for cryogenic stability and the quench propagation velocity along the leads are compared for various parts of the Magnet leads inside the cold mass cryostat. The effect of the insulation on leads on heat transfer is and stability is discussed.

  8. Direct quantitative detection of Doc2b-induced hemifusion in optically trapped membranes

    PubMed Central

    Brouwer, Ineke; Giniatullina, Asiya; Laurens, Niels; van Weering, Jan R. T.; Bald, Dirk; Wuite, Gijs J. L.; Groffen, Alexander J.

    2015-01-01

    Ca2+-sensor proteins control the secretion of many neuroendocrine substances. Calcium-secretion coupling may involve several mechanisms. First, Ca2+-dependent association of their tandem C2 domains with phosphatidylserine may induce membrane curvature and thereby enhance fusion. Second, their association with SNARE complexes may inhibit membrane fusion in the absence of a Ca2+ trigger. Here we present a method using two optically trapped beads coated with SNARE-free synthetic membranes to elucidate the direct role of the C2AB domain of the soluble Ca2+-sensor Doc2b. Contacting membranes are often coupled by a Doc2b-coated membrane stalk that resists forces up to 600 pN upon bead separation. Stalk formation depends strictly on Ca2+ and phosphatidylserine. Real-time fluorescence imaging shows phospholipid but not content mixing, indicating membrane hemifusion. Thus, Doc2b acts directly on membranes and stabilizes the hemifusion intermediate in this cell-free system. In living cells, this mechanism may co-occur with progressive SNARE complex assembly, together defining Ca2+-secretion coupling. PMID:26395669

  9. APOSTLE: LONGTERM TRANSIT MONITORING AND STABILITY ANALYSIS OF XO-2b

    SciTech Connect

    Kundurthy, P.; Barnes, R.; Becker, A. C.; Agol, E.; Williams, B. F.; Rose, A.; Gorelick, N.

    2013-06-10

    The Apache Point Survey of Transit Lightcurves of Exoplanets (APOSTLE) observed 10 transits of XO-2b over a period of 3 yr. We present measurements that confirm previous estimates of system parameters like the normalized semi-major axis (a/R{sub *}), stellar density ({rho}{sub *}), impact parameter (b), and orbital inclination (i{sub orb}). Our errors on system parameters like a/R{sub *} and {rho}{sub *} have improved by {approx}40% compared to previous best ground-based measurements. Our study of the transit times show no evidence for transit timing variations (TTVs) and we are able to rule out co-planar companions with masses {>=}0.20 M{sub Circled-Plus} in low order mean motion resonance with XO-2b. We also explored the stability of the XO-2 system given various orbital configurations of a hypothetical planet near the 2:1 mean motion resonance. We find that a wide range of orbits (including Earth-mass perturbers) are both dynamically stable and produce observable TTVs. We find that up to 51% of our stable simulations show TTVs that are smaller than the typical transit timing errors ({approx}20 s) measured for XO-2b, and hence remain undetectable.

  10. A population-specific HTR2B stop codon predisposes to severe impulsivity.

    PubMed

    Bevilacqua, Laura; Doly, Stéphane; Kaprio, Jaakko; Yuan, Qiaoping; Tikkanen, Roope; Paunio, Tiina; Zhou, Zhifeng; Wedenoja, Juho; Maroteaux, Luc; Diaz, Silvina; Belmer, Arnaud; Hodgkinson, Colin A; Dell'osso, Liliana; Suvisaari, Jaana; Coccaro, Emil; Rose, Richard J; Peltonen, Leena; Virkkunen, Matti; Goldman, David

    2010-12-23

    Impulsivity, describing action without foresight, is an important feature of several psychiatric diseases, suicidality and violent behaviour. The complex origins of impulsivity hinder identification of the genes influencing it and the diseases with which it is associated. Here we perform exon-focused sequencing of impulsive individuals in a founder population, targeting fourteen genes belonging to the serotonin and dopamine domain. A stop codon in HTR2B was identified that is common (minor allele frequency > 1%) but exclusive to Finnish people. Expression of the gene in the human brain was assessed, as well as the molecular functionality of the stop codon, which was associated with psychiatric diseases marked by impulsivity in both population and family-based analyses. Knockout of Htr2b increased impulsive behaviours in mice, indicative of predictive validity. Our study shows the potential for identifying and tracing effects of rare alleles in complex behavioural phenotypes using founder populations, and indicates a role for HTR2B in impulsivity. PMID:21179162

  11. Employing complex polyhierarchical ontologies and promoting interoperability of i2b2 data systems

    PubMed Central

    Campbell, James Richard; Campbell, Walter Scott; Hickman, Hubert; Pedersen, Jay; McClay, James

    2015-01-01

    I2b2 is in widespread use for managing research data warehouses. It employs reference ontologies as a record index and supports searching for aggregate cases using a pattern match operator on ASCII strings representing the node traversal from root to concept(PATHs). This creates complexities in dissemination and deployment for large polyhierarchical ontologies such as SNOMED CT. We hypothesized that an alternative approach employing transitive closure tables (TC) could lead to more accurate, efficient and interoperable search tools for i2b2. We evaluated search speed, accuracy and interoperability of queries employing each approach. We found both TC-based and PATH-based queries to produce accurate results. However, we observed that TC-based queries involving concepts included in large numbers of paths ran substantially faster than PATH-based queries for the same concept. Oracle query plan resource estimates differed by one to three orders of magnitude for these queries. We conclude that a simplification of dissemination tools for SNOMED CT and revision in the metadata build for i2b2 can effectively employ SNOMED CT with increased efficiency and comparable accuracy. Use of transitive closure tables in metadata can promote network query interoperability. PMID:26958167

  12. CRL4(Wdr70) regulates H2B monoubiquitination and facilitates Exo1-dependent resection.

    PubMed

    Zeng, Ming; Ren, Laifeng; Mizuno, Ken'Ichi; Nestoras, Konstantinos; Wang, Haibin; Tang, Zizhi; Guo, Liandi; Kong, Daochun; Hu, Qiwen; He, Qun; Du, Lilin; Carr, Antony M; Liu, Cong

    2016-01-01

    Double-strand breaks repaired by homologous recombination (HR) are first resected to form single-stranded DNA, which binds replication protein A (RPA). RPA attracts mediators that load the Rad51 filament to promote strand invasion, the defining feature of HR. How the resection machinery navigates nucleosome-packaged DNA is poorly understood. Here we report that in Schizosaccharomyces pombe a conserved DDB1-CUL4-associated factor (DCAF), Wdr70, is recruited to DSBs as part of the Cullin4-DDB1 ubiquitin ligase (CRL4(Wdr70)) and stimulates distal H2B lysine 119 mono-ubiquitination (uH2B). Wdr70 deletion, or uH2B loss, results in increased loading of the checkpoint adaptor and resection inhibitor Crb2(53BP1), decreased Exo1 association and delayed resection. Wdr70 is dispensable for resection upon Crb2(53BP1) loss, or when the Set9 methyltransferase that creates docking sites for Crb2 is deleted. Finally, we establish that this histone regulatory cascade similarly controls DSB resection in human cells. PMID:27098497

  13. Magnetism and superconductivity in (HoxY1-x)Ni2B2C

    NASA Astrophysics Data System (ADS)

    Müller, Karl-Hartmut; Fuchs, Günter; Handstein, Axel; Cao, Lei; Eversmann, Kathrin

    1996-02-01

    The pseudoquarternary system (HoxY1-x)Ni2B2C, has been investigated by resistance and magnetization measurements. A linear depression of the superconducting transition temperature Tc found with increasing Ho content is interpreted in the framework of the Abrikosov-Gor'kov theory which predicts also a linear scaling of Tc with the de Gennes factor of the rare earth elements R of the RNi2B2C family. We found that both cases follow a common linear scaling behaviour including the superconducting transition and the magnetic ordering temperature. A reentrant behaviour observed for Ho contents x≥0.5 results in maxima in the temperature dependence of the upper critical field Hc2(T), which are compared with Hc2(T) data of TmNi2B2C. In the paramagnetic range of field and temperature the sample magnetization can be described by a Brillouin function with a Ho-moment of 10.5 μ B.

  14. Histone demethylase JMJD2B and JMJD2C induce fibroblast growth factor 2: mediated tumorigenesis of osteosarcoma.

    PubMed

    Li, Xiaojiang; Dong, Shanshan

    2015-03-01

    JMJD2B and JMJD2C, histone demethylases, play crucial roles in cancer development and are up-regulated in many cancers. However, the actions of JMJD2B and JMJD2C in osteosarcoma remain unknown. The levels of JMJD2B or JMJD2C were evaluated in osteosarcoma cells and tissues via quantitative real-time PCR and Western Blot. JMJD2B and JMJD2C were up-regulated in osteosarcoma tissues when compared to paired adjacent non-tumor tissues. A higher level of JMJD2B or JMJD2C was related with metastasis of osteosarcoma cells. Fibroblast growth factor 2 (FGF2) is an important factor to maintain immaturity of cells and contributes to osteosarcoma aggressiveness. Elevated levels of FGF2 promoted the proliferation, migration, and invasion of osteosarcoma cell, while FGF2 was up-regulated by JMJD2B or JMJD2C. GST pull-down assay showed that JMJD2B or JMJD2C interacted with FGF2. Thus, JMJD2B and JMJD2C play an important role in the pathology of osteosarcoma via the up-regulation of FGF2. JMJD2B and JMJD2C should be developed potential targets for the therapy of osteosarcoma patients. PMID:25636512

  15. KDM2B/FBXL10 targets c-Fos for ubiquitylation and degradation in response to mitogenic stimulation

    PubMed Central

    Han, Xiao-Ran; Zha, Zhengyu; Yuan, Hai-Xin; Feng, Xu; Xia, Yu-Kun; Lei, Qun-Ying; Guan, Kun-Liang; Xiong, Yue

    2015-01-01

    SUMMARY KDM2B (also known as FBXL10) controls stem cell self-renewal, somatic cell reprogramming and senescence, and tumorigenesis. KDM2B contains multiple functional domains, including a JmjC domain that catalyzes H3K36 demethylation and a CxxC zing finger that recognizes CpG islands and recruits the polycomb repressive complex 1 (PRC1). Here, we report that KDM2B, via its F-box domain, functions as a subunit of the CUL1-RING ubiquitin ligase (CRL1/SCFKDM2B) complex. KDM2B targets c-Fos for polyubiquitylation and regulates c-Fos protein levels. Unlike the phosphorylation of other SCF/CRL1 substrates that promotes substrates binding to F-box, EGF-induced c-Fos S374 phosphorylation dissociates c-Fos from KDM2B and stabilizes c-Fos protein. Non-phosphorylatable and phosphomimetic mutations at S374 result in c-Fos protein which cannot be induced by EGF and accumulates constitutively and lead to decreased or increased cell proliferation, respectively. Multiple tumor-derived KDM2B mutations impaired the function of KDM2B to target c-Fos degradation and to suppress cell proliferation. These results reveal a novel function of KDM2B in the negative regulation of cell proliferation by assembling an E3 ligase to targeting c-Fos protein degradation that is antagonized by mitogenic stimulations. PMID:26725323

  16. Cytochrome P450 Oxidoreductase Influences CYP2B6 Activity in Cyclophosphamide Bioactivation

    PubMed Central

    El-Serafi, Ibrahim; Afsharian, Parvaneh; Moshfegh, Ali; Hassan, Moustapha; Terelius, Ylva

    2015-01-01

    Introduction Cyclophosphamide is commonly used as an important component in conditioning prior to hematopoietic stem cell transplantation, a curative treatment for several hematological diseases. Cyclophosphamide is a prodrug activated mainly by cytochrome P450 2B6 (CYP2B6) in the liver. A high degree of inter- and intra-individual variation in cyclophosphamide kinetics has been reported in several studies. Materials and Methods Hydroxylation of cyclophosphamide was investigated in vitro using three microsomal batches of CYP2B6*1 with different ratios of POR/CYP expression levels. Twenty patients undergoing hematopoietic stem cell transplantation were also included in the study. All patients received an i.v. infusion of cyclophosphamide (60 mg/kg/day, for two days) as a part of their conditioning. Blood samples were collected from each patient before cyclophosphamide infusion, 6 h after the first dose and before and 6 h after the second dose. POR gene expression was measured by mRNA analysis and the pharmacokinetics of cyclophosphamide and its active metabolite were determined. Results A strong correlation between the in vitro intrinsic clearance of cyclophosphamide and the POR/CYP ratio was found. The apparent Km for CYP2B6.1 was almost constant (3-4 mM), while the CLint values were proportional to the POR/CYP ratio (3-34 μL/min/nmol CYP). In patients, the average expression of the POR gene in blood was significantly (P <0.001) up-regulated after cyclophosphamide infusion, with high inter-individual variations and significant correlation with the concentration ratio of the active metabolite 4-hydroxy-cyclophosphamide/cyclophosphamide. Nine patients were carriers for POR*28; four patients had relatively high POR expression. Conclusions This investigation shows for the first time that POR besides CYP2B6 can influence cyclophosphamide metabolism. Our results indicate that not only CYPs are important, but also POR expression and/or activity may influence

  17. Oxidative metabolism of BDE-99 by human liver microsomes: predominant role of CYP2B6.

    PubMed

    Erratico, Claudio A; Szeitz, András; Bandiera, Stelvio M

    2012-10-01

    Hydroxylated polybrominated diphenyl ethers (PBDEs) have been found in human serum, suggesting that they are formed by in vivo oxidative metabolism of PBDEs. However, the biotransformation of 2,2',4,4',5-pentabromodiphenyl ether (BDE-99), a major PBDE detected in human tissue and environmental samples, is poorly understood. In the present study, the oxidative metabolism of BDE-99 was assessed using pooled and single-donor human liver microsomes, a panel of human recombinant cytochrome P450 (CYP) enzymes, and CYP-specific antibodies. Hydroxylated metabolites were quantified using a liquid chromatography/tandem mass spectrometry-based method. In total, 10 hydroxylated metabolites of BDE-99 were produced by human liver microsomes. Six metabolites were identified as 2,4,5-tribromophenol (2,4,5-TBP), 4-OH-BDE-90, 5'-OH-BDE-99, 6'-OH-BDE-99, 4'-OH-BDE-101, and 2-OH-BDE-123 using authentic standards. Three monohydroxy- and one dihydroxy-pentabrominated metabolites were unidentified. Rates of formation of the three major metabolites (2,4,5-TBP, 5'-OH-BDE-99, and 4'-OH-BDE-101) by human liver microsomes ranged from 24.4 to 44.8 pmol/min/mg protein. Additional experiments demonstrated that the dihydroxylated metabolite was a primary metabolite of BDE-99 and was not produced by hydroxylation of a monohydroxy metabolite. Among the panel of recombinant CYP enzymes tested, formation of all 10 hydroxylated metabolites was catalyzed solely by CYP2B6. A combined approach using antibodies to CYP2B6 and single-donor liver microsomes expressing a wide range of CYP2B6 levels confirmed that CYP2B6 was responsible for the biotransformation of BDE-99. Collectively, the results show that the oxidative metabolism of BDE-99 by human liver microsomes is catalyzed solely by CYP2B6 and is an important determinant of the toxicity and bioaccumulation of BDE-99 in humans. PMID:22738989

  18. Vom Urknall zum Zerfall. Die Welt zwischen Anfang und Ende.

    NASA Astrophysics Data System (ADS)

    Fritzsch, H.

    Contents: Der Tanz mit dem Ozean. Galaktische Landkarte. Das Maß der Dinge. Der würfelnde Gott der Quantenphysik. Geheimnisvolle Felder. Materie und Antimaterie. Quarks - Urstoff unserer Welt. Zerfallende Protonen und die Einheit der Physik. Der Zauberofen. Das überschaubare Universum. Das explodierende Universum. Nachhall der Schöpfung. Der achtfache Weg der kosmischen Entwicklung. Das Ende der Welt. Einheit in der Vielfalt. Das geistige Universum. Gott und das absurde Universum.

  19. Das menschliche Gehör und Grundlagen der Psychoakustik

    NASA Astrophysics Data System (ADS)

    Genuit, Klaus; Sottek, Roland

    Das menschliche Gehör ist ein äußerst komplexes Empfangs- und Signalverarbeitungssystem. Es ist als Schallanalysator in Leistungsfähigkeit und Vielseitigkeit von technisch-analytischen Verfahren nach wie vor unerreicht. Die Signalverarbeitung läuft auf Grundlage komplexer Prozesse ab, die in ihrer Gesamtheit bislang nicht vollständig erfasst sind. Verschiedene Modelle zur gehörgerechten Zeit- und Frequenzanalyse ahmen jene komplexen Prozesse und Verarbeitungsmechanismen nach, die im menschlichen Gehör vollzogen werden.

  20. MAT2B promotes adipogenesis by modulating SAMe levels and activating AKT/ERK pathway during porcine intramuscular preadipocyte differentiation.

    PubMed

    Zhao, Cunzhen; Chen, Xiaochang; Wu, Wenjing; Wang, Wusu; Pang, Weijun; Yang, Gongshe

    2016-05-15

    Intramuscular fat (IMF) has been demonstrated as one of the crucial factors of livestock meat quality. The MAT2B protein with MAT2α catalyzes the formation of methyl donor S- adenosylmethionine (SAMe) to mediate cell metabolism including proliferation and apoptosis. However, the regulatory effect of MAT2B on IMF deposition is still unclear. In this study, the effect of MAT2B on adipogenesis and its potential mechanism during porcine intramuscular preadipocyte differentiation was studied. The results showed that overexpression of MAT2B promoted adipogenesis and significantly up-regulated the mRNA and protein levels of adipogenic marker genes including FASN, PPARγ and aP2, consistently, knockdown of MAT2B inhibited lipid accumulation and down-regulated the mRNA and protein levels of the above genes. Furthermore, flow cytometry and EdU-labeling assay indicated that MAT2B regulate adipogenesis was partly due to influence intracellular SAMe levels and further affect cell clonal expansion. Also, increased expression of MAT2B activated the phosphorylations of AKT and ERK1/2, whereas knockdown of MAT2B blocked AKT signaling and repressed the phosphorylation of ERK1/2. Moreover, the inhibitory effect of LY294002 (a specific PI3K inhibitor) on the activities of AKT and ERK1/2 was partially recovered by overexpression of MAT2B in porcine intramuscular adipocytes. Finally, Co-IP experiments showed that MAT2B can directly interact with AKT. Taken together, our findings suggested that MAT2B acted as a positive regulator through modifying SAMe levels as well as activating AKT/ERK signaling pathway to promote porcine intramuscular adipocyte differentiation. PMID:26940012

  1. Setdb1 histone methyltransferase regulates mood-related behaviors and expression of the NMDA receptor subunit NR2B.

    PubMed

    Jiang, Yan; Jakovcevski, Mira; Bharadwaj, Rahul; Connor, Caroline; Schroeder, Frederick A; Lin, Cong L; Straubhaar, Juerg; Martin, Gilles; Akbarian, Schahram

    2010-05-26

    Histone methyltransferases specific for the histone H3-lysine 9 residue, including Setdb1 (Set domain, bifurcated 1)/Eset/Kmt1e are associated with repressive chromatin remodeling and expressed in adult brain, but potential effects on neuronal function and behavior remain unexplored. Here, we report that transgenic mice with increased Setdb1 expression in adult forebrain neurons show antidepressant-like phenotypes in behavioral paradigms for anhedonia, despair, and learned helplessness. Chromatin immunoprecipitation in conjunction with DNA tiling arrays (ChIP-chip) revealed that genomic occupancies of neuronal Setdb1 are limited to <1% of annotated genes, which include the NMDA receptor subunit NR2B/Grin2B and other ionotropic glutamate receptor genes. Chromatin conformation capture and Setdb1-ChIP revealed a loop formation tethering the NR2B/Grin2b promoter to the Setdb1 target site positioned 30 kb downstream of the transcription start site. In hippocampus and ventral striatum, two key structures in the neuronal circuitry regulating mood-related behaviors, Setdb1-mediated repressive histone methylation at NR2B/Grin2b was associated with decreased NR2B expression and EPSP insensitivity to pharmacological blockade of NR2B, and accelerated NMDA receptor desensitization consistent with a shift in NR2A/B subunit ratios. In wild-type mice, systemic treatment with the NR2B antagonist, Ro25-6981 [R-(R,S)-alpha-(4-hydroxyphenyl)-beta-methyl-4-(phenylmethyl)-1-piperidine propranol], and hippocampal small interfering RNA-mediated NR2B/Grin2b knockdown resulted in behavioral changes similar to those elicited by the Setdb1 transgene. Together, these findings point to a role for neuronal Setdb1 in the regulation of affective and motivational behaviors through repressive chromatin remodeling at a select set of target genes, resulting in altered NMDA receptor subunit composition and other molecular adaptations. PMID:20505083

  2. Jumonji domain-containing protein 2B silencing induces DNA damage response via STAT3 pathway in colorectal cancer

    PubMed Central

    Chen, L; Fu, L; Kong, X; Xu, J; Wang, Z; Ma, X; Akiyama, Y; Chen, Y; Fang, J

    2014-01-01

    Background: Jumonji domain-containing protein 2B (JMJD2B), directly targeted by hypoxia-inducible factor 1α, maintains the histone methylation balance important for the transcriptional activation of many oncogenes. Jumonji domain-containing protein 2B has been implicated in colorectal cancer (CRC) progression; however, the mechanism remains unclear. Methods: Immunofluorescence and western blotting detected phosphorylated histone H2AX, characteristic of double-strand breaks, and comet assay was used to investigate DNA damage, in CRC cells after JMJD2B small interfering RNA (siRNA) transfection. We assessed the resulting in vitro responses, that is, cell cycle progression, apoptosis, and senescence coupled with JMJD2B silencing-induced DNA damage, studying the regulatory role of signal transducers and activators of transcription 3 (STAT3). The JMJD2B silencing anti-cancer effect was determined using an in vivo CRC xenograft model. Results: Jumonji domain-containing protein 2B knockdown induced DNA damage via ataxia telangiectasia-mutated (ATM) and ATM and Rad3-related pathway activation, resulting in cell cycle arrest, apoptosis, and senescence in both normoxia and hypoxia. Signal transducers and activators of transcription 3 suppression by JMJD2B silencing enhanced DNA damage. Intratumoural injection of JMJD2B siRNA suppressed tumour growth in vivo and activated the DNA damage response (DDR). Conclusions: Jumonji domain-containing protein 2B has an essential role in cancer cell survival and tumour growth via DDR mediation, which STAT3 partially regulates, suggesting that JMJD2B is a potential anti-cancer target. PMID:24473398

  3. Influence of P ion on Sr2B5O9Cl:Eu for TL dosimetry

    NASA Astrophysics Data System (ADS)

    Oza, Abha H.; Dhoble, N. S.; Dhoble, S. J.

    2015-02-01

    This paper investigates luminescence properties of Sr2B5O9Cl:Eu phosphor prepared by modified solid state diffusion. The influence of Phosphorous ion as codopant is also explained in detail. The structural confirmation of the sample was done using the XRD technique. SEM revealed the microcrystalline nature of the prepared phosphor. The characteristic Eu2+ emission at 437 nm and 423 nm was observed for Sr2B5O9Cl:Eu and Sr2B5O9Cl:P,Eu, respectively under 338 nm excitation. Samples in powder form were irradiated with different doses under γ-ray irradiation with 60Co source and the TL glow curves for both Sr2B5O9Cl:Eu and Sr2B5O9Cl:P,Eu samples were studied. In case of Sr2B5O9Cl:Eu phosphor, single glow curve nature centered on 260 °C with a shoulder peak around 144 °C was observed. However; Sr2B5O9Cl:P,Eu have shown slight different and broad glow curve nature. The TL sensitivity in both the cases was compared with CaSO4:Dy phosphor. Sr2B5O9Cl:Eu sample have shown 1.17 times less sensitivity than CaSO4:Dy and for Sr2B5O9Cl:P,Eu it was found to be equal to CaSO4:Dy and Sr2B5O9Cl:P,Eu is 1.21 times more sensitive than Sr2B5O9Cl:Eu. Other TL properties like dose response, fading and reusability were studied for both the samples. The trapping parameters for both the samples were calculated using computerized glow curve deconvolution and reported in this paper.

  4. Transcriptional Regulation of CYP2B6 Expression by Hepatocyte Nuclear Factor 3β in Human Liver Cells

    PubMed Central

    Li, Linhao; Li, Daochuan; Heyward, Scott; Wang, Hongbing

    2016-01-01

    CYP2B6 plays an increasingly important role in xenobiotic metabolism and detoxification. The constitutive androstane receptor (CAR) and the pregnane X receptor (PXR) have been established as predominant regulators for the inductive expression of CYP2B6 gene in human liver. However, there are dramatic interindividual variabilities in CYP2B6 expression that cannot be fully explained by the CAR/PXR-based modulation alone. Here, we show that expression level of CYP2B6 was correlated with that of hepatocyte nuclear factor 3β (HNF3β) in human primary hepatocytes prepared from 35 liver donors. Utilizing recombinant virus-mediated overexpression or knockdown of HNF3β in HepG2 cells, as well as constructs containing serial deletion and site-directed mutation of HNF3β binding motifs in CYP2B6 luciferase reporter assays, we demonstrated that the presence or lack of HNF3β expression markedly correlated with CYP2B6 gene expression and its promoter activity. Novel enhancer modules of HNF3β located upstream of the CYP2B6 gene transcription start site were identified and functionally validated as key elements governing HNF3β-mediated CYP2B6 expression. Chromatin immunoprecipitation assays in human primary hepatocytes and surface plasmon resonance binding affinity experiments confirmed the essential role of these enhancers in the recruitment of HNF3β to the promoter of CYP2B6 gene. Overall, these findings indicate that HNF3β represents a new liver enriched transcription factor that is involved in the transcription of CYP2B6 gene and contributes to the large interindividual variations of CYP2B6 expression in human population. PMID:26930610

  5. Characterization of CYP2B6 in a CYP2B6-Humanized Mouse Model: Inducibility in the Liver by Phenobarbital and Dexamethasone and Role in Nicotine Metabolism In Vivo

    PubMed Central

    Liu, Zhihua; Li, Lei; Wu, Hong; Hu, Jing; Ma, Jun; Zhang, Qing-Yu

    2015-01-01

    The aim of this study was to further characterize the expression and function of human CYP2B6 in a recently generated CYP2A13/2B6/2F1-transgenic (TG) mouse model, in which CYP2B6 is expressed selectively in the liver. The inducibility of CYP2B6 by phenobarbital (PB) and dexamethasone (DEX), known inducers of CYP2B6 in human liver, was examined in the TG mice, as well as in TG/Cyp2abfgs-null (or “CYP2B6-humanized”) mice. Hepatic expression of CYP2B6 mRNA and protein was greatly induced by PB or DEX treatment in both TG and TG/Cyp2abfgs-null mice. Function of the transgenic CYP2B6 was first studied using bupropion as a probe substrate. In PB-treated mice, the rates of hepatic microsomal hydroxybupropion formation (at 50 μM bupropion) were >4-fold higher in TG/Cyp2abfgs-null than in Cyp2abfgs-null mice (for both male and female mice); the rate difference was accompanied by a 5-fold higher catalytic efficiency in the TG/Cyp2abfgs-null mice and was abolished by an antibody to CYP2B6. The ability of CYP2B6 to metabolize nicotine was then examined, both in vitro and in vivo. The rates of hepatic microsomal cotinine formation from nicotine were significantly higher in TG/Cyp2abfgs-null than in Cyp2abfgs-null mice, pretreated with PB or DEX. Furthermore, systemic nicotine metabolism was faster in TG/Cyp2abfgs-null than in Cyp2abfgs-null mice. Thus, the transgenic CYP2B6 was inducible and functional, and, in the absence of mouse CYP2A and CYP2B enzymes, it contributed to nicotine metabolism in vivo. The CYP2B6-humanized mouse will be valuable for studies on in vivo roles of hepatic CYP2B6 in xenobiotic metabolism and toxicity. PMID:25409894

  6. Supraleitung und Interkontinentalraketen „On-line computing“ zwischen Militär, Industrie und Wissenschaft

    NASA Astrophysics Data System (ADS)

    Knolle, Johannes; Joas, Christian

    Der zweite Weltkrieg und der Kalte Krieg veränderten nicht nur das Verhältnis zwischen Militär, Industrie und Wissenschaft, sondern auch die wissenschaftliche Praxis von Physikern und anderen Wissenschaftlern. In den 1950er Jahren stellte die Entwicklung von Interkontinentalraketen die Auftragnehmer des Militärs in der Industrie vor komplexe Fragestellungen, zu deren Lösung sie auf die Expertise von Wissenschaftlern angewiesen waren. Industrieunternehmen gründeten eigene Forschungseinheiten zur Lösung technischer und wissenschaftlicher Probleme.

  7. 76 FR 59896 - Wage Methodology for the Temporary Non-Agricultural Employment H-2B Program; Postponement of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-28

    ... Employment H-2B Program; Final Rule, 76 FR 3452, Jan. 19, 2011, (the Wage Rule). The Wage Rule revised the... Employment H-2B Program; Amendment of Effective Date; Final Rule, 76 FR 45667, August 1, 2011 revised the.... DATES: The effective date of the rule amending 20 CFR part 655 published at 76 FR 45667, August 1,...

  8. 76 FR 73508 - Wage Methodology for the Temporary Non-Agricultural Employment H-2B Program; Delay of Effective Date

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-29

    ... Employment H-2B Program; Final Rule, 76 FR 3452, Jan. 19, 2011, (the Wage Rule) to January 1, 2012 in... 655, published at 76 FR 45667, August 1, 2011, as further amended at 76 FR 59896, September 28, 2011... Employment H-2B Program; Final Rule (the Wage Rule) on January 19, 2011, 76 FR 3452. The Wage Rule...

  9. Deletion of JMJD2B in neurons leads to defective spine maturation, hyperactive behavior and memory deficits in mouse

    PubMed Central

    Fujiwara, K; Fujita, Y; Kasai, A; Onaka, Y; Hashimoto, H; Okada, H; Yamashita, T

    2016-01-01

    JMJD2B is a histone demethylase enzyme that regulates gene expression through demethylation of H3K9me3. Although mutations of JMJD2B have been suggested to be responsible for neurodevelopmental disorders, the function of JMJD2B in the central nervous system (CNS) remains to be elucidated. Here we show that JMJD2B has a critical role in the development of the CNS. We observed JMJD2B expression, which was especially strong in the hippocampus, throughout the CNS from embryonic periods through adulthood. We generated neuron-specific JMJD2B-deficient mice using the cre-loxP system. We found an increase in total spine number, but a decrease in mature spines, in the CA1 region of the hippocampus. JMJD2B-deficient mice exhibited hyperactive behavior, sustained hyperactivity in a novel environment, deficits in working memory and spontaneous epileptic-like seizures. Together these observations indicate that JMJD2B mutant mice display symptoms reminiscent of neurodevelopmental disorders. Our findings provide evidence for the involvement of histone demethylation in the formation of functional neural networks during development. PMID:27023172

  10. Suppression of CYP2B Induction by Alendronate-Mediated Farnesyl Diphosphate Synthase Inhibition in Primary Cultured Rat Hepatocytes

    PubMed Central

    Jackson, Nancy M.; Kocarek, Thomas A.

    2008-01-01

    We previously reported that squalestatin 1-mediated induction of CYP2B expression is attributable to squalene synthase inhibition and accumulation of an endogenous isoprenoid(s) that is capable of activating the constitutive androstane receptor. To determine whether squalestatin 1-mediated CYP2B induction is strictly dependent upon the biosynthesis of farnesyl pyrophosphate (FPP), the substrate for squalene synthase, the effects of alendronate, a nitrogen-containing bisphosphonate inhibitor of farnesyl diphosphate synthase, were determined on basal, squalestatin 1-inducible, and phenobarbital-inducible CYP2B expression in primary cultured rat hepatocytes. Alendronate treatment alone had no effect on CYP2B or CYP3A mRNA expression in the hepatocyte cultures, but alendronate co-treatment completely suppressed squalestatin 1-mediated CYP2B mRNA induction at concentrations (60 and 100 μM) that effectively inhibited cellular farnesyl diphosphate synthase activity, as assessed by reductions of squalestatin 1-mediated FPP accumulation, and that were not toxic to the cells, as indicated by a lack of effect on MTT activity. Alendronate co-treatment also partially suppressed phenobarbital-inducible CYP2B expression, and this suppressive effect was attenuated by additional co-treatment with the upstream pathway inhibitor, pravastatin. These findings demonstrate that squalestatin 1-mediated CYP2B induction cannot occur in the absence of FPP biosynthesis, but also indicate that one or more upstream isoprenoids, possibly isopentenyl pyrophosphate and/or dimethylallyl pyrophosphate, function to antagonize the CYP2B induction process. PMID:18617600

  11. 77 FR 28764 - Temporary Non-agricultural Employment of H-2B Aliens in the United States

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-05-16

    ... published a Final Rule amending the H-2B regulations at 20 CFR part 655, Subpart A. 77 FR 10038, February 21... Agriculture or Registered Nursing in the United States (H-2B Workers), and Other Technical Changes, 73 FR... INFORMATION CONTACT: For further information, contact William L. Carlson, Ph.D., Administrator, Office...

  12. 50 CFR Table 2b to Part 660... - 2014, and Beyond, Allocations by Species or Species Group

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 50 Wildlife and Fisheries 13 2014-10-01 2014-10-01 false 2014, and Beyond, Allocations by Species or Species Group 2b Table 2b to Part 660, Subpart C Wildlife and Fisheries FISHERY CONSERVATION AND MANAGEMENT, NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE (CONTINUED) FISHERIES...

  13. Structural evidence for Nap1-dependent H2A-H2B deposition and nucleosome assembly.

    PubMed

    Aguilar-Gurrieri, Carmen; Larabi, Amédé; Vinayachandran, Vinesh; Patel, Nisha A; Yen, Kuangyu; Reja, Rohit; Ebong, Ima-O; Schoehn, Guy; Robinson, Carol V; Pugh, B Franklin; Panne, Daniel

    2016-07-01

    Nap1 is a histone chaperone involved in the nuclear import of H2A-H2B and nucleosome assembly. Here, we report the crystal structure of Nap1 bound to H2A-H2B together with in vitro and in vivo functional studies that elucidate the principles underlying Nap1-mediated H2A-H2B chaperoning and nucleosome assembly. A Nap1 dimer provides an acidic binding surface and asymmetrically engages a single H2A-H2B heterodimer. Oligomerization of the Nap1-H2A-H2B complex results in burial of surfaces required for deposition of H2A-H2B into nucleosomes. Chromatin immunoprecipitation-exonuclease (ChIP-exo) analysis shows that Nap1 is required for H2A-H2B deposition across the genome. Mutants that interfere with Nap1 oligomerization exhibit severe nucleosome assembly defects showing that oligomerization is essential for the chaperone function. These findings establish the molecular basis for Nap1-mediated H2A-H2B deposition and nucleosome assembly. PMID:27225933

  14. 77 FR 24225 - Information Collection Approval; Temporary Non-Agricultural Employment of H-2B Aliens in the...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-23

    ... Employment of H-2B Aliens in the United States; Final Rule. See 77 FR 10038, Feb. 21, 2012. DATES: On April 8....gov/fdsys/browse/collection.action?collectionCode=FR Web site. Copies of this notice may be obtained..., 2012. See 77 FR 10038. The purpose of the Final Rule was to amend the H-2B regulations at 20 CFR...

  15. Impact of UGT2B17 Gene Deletion on the Pharmacokinetics of 17-Hydroexemestane in Healthy Volunteers.

    PubMed

    Chen, Shanly M; Atchley, Daniel H; Murphy, Michael A; Gurley, Bill J; Kamdem, Landry K

    2016-07-01

    Exemestane is an aromatase inhibitor drug used for the treatment of hormone-dependent breast cancer. 17-Hydroexemestane, the major and biologically active metabolite of exemestane in humans, is eliminated via glucuronidation by the polymorphic UGT2B17 phase II drug-metabolizing enzyme. Previous microsomal studies have shown that UGT2B17 gene deletion affects the intrinsic hepatic clearances of 17-hydroexemestane in vitro. In this open-label study we set out to assess the effect of UGT2B17 gene deletion on the pharmacokinetics of 17-hydroexemestane in healthy female volunteers with and without UGT2B17. To achieve this goal, 14 healthy postmenopausal women (8 carriers of the homozygous UGT2B17 wild-type allele and 6 carriers of the homozygous UGT2B17 gene-deletion allele) were enrolled and invited to receive a single 25-mg oral dose of exemestane. Pharmacokinetics was assessed over 72 hours postdosing. Our results showed that there were statistically significant differences in plasma 17-hydroexemestane AUC0-∞ (P = .0007) and urine 17-hydroexemestane C24h (P = .001) between UGT2B17 genotype groups. Our data suggest that UGT2B17 gene deletion influences 17-hydroexemestane pharmacokinetics in humans. PMID:26608382

  16. Atomic force microscopy revelation of molecular complexes in the multiprotein cytochrome P450 2B4-containing system.

    PubMed

    Kuznetsov, Vadim Yu; Ivanov, Yuri D; Archakov, Alexander I

    2004-08-01

    The application of atomic force microscopy (AFM) to the identification and visualization of individual molecules and their complexes in a reconstituted monooxygenase P450 2B4 system without the phospholipid was demonstrated. The method employed in this study distinguishes the monomeric proteins from their binary complexes and, also, the binary from the ternary complexes. The AFM images of the full-length P450 2B4 system's constituent components - cytochrome P450 2B4 (2B4), NADPH-cytochrome P450 reductase and cytochrome b5 (b5), were obtained on highly-oriented pyrolitic graphite. The typical heights of the d-2B4, d-flavoprotein (Fp) and d-b5 molecules were measured and found to be 2.2 +/- 0.2, 2.3 +/- 0.2 and 1.8 +/- 0.1 nm, respectively. The measured heights of the binary d-Fp/d-2B4 and d-2B4/d-b5 complexes were estimated to be 3.4 +/- 0.2 and 2.8 +/- 0.2 nm, respectively. No formation of d-Fp/d-b5 complexes was registered. The ternary d-Fp/d-2B4/d-b5 complexes were visualized and their heights were found to be roughly equal to 4.3 +/- 0.3 nm and 6.2 +/- 0.3 nm. PMID:15274134

  17. Modulation of natural killer cell functions by interactions between 2B4 and CD48 in cis and in trans

    PubMed Central

    Claus, Maren; Wingert, Sabine

    2016-01-01

    SLAM-related receptors (SRRs) are important modulators of immune cell function. While most SRRs are homophilic, 2B4 (CD244) interacts with CD48, a GPI-anchored protein expressed on many haematopoietic cells. Here we show that natural killer (NK) cell-expressed 2B4 not only binds in trans to CD48 on neighbouring cells but also interacts in cis with CD48 on the same cell. 2B4 uses the same binding site to interact with CD48 in cis and in trans and structural flexibility of 2B4 is necessary for the cis interaction. Furthermore, the cis interaction is sufficient to induce basal phosphorylation of 2B4. However, cis interaction reduces the ability of 2B4 to bind CD48 in trans. As a consequence, stimulation-dependent phosphorylation of 2B4 upon binding to CD48 positive target cells is reduced. Interfering with the cis interaction therefore enhanced the lysis of CD48-expressing tumour cells. These data show that the density of 2B4 and CD48 on both the NK cell and the potential target cell modulates NK cell activity. PMID:27249817

  18. 3 CFR - Presidential Determination for the Kingdom of Cambodia Under Section 2(b)(2) of the Export-Import...

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... Cambodia Under Section 2(b)(2) of the Export-Import Bank Act of 1945, as amended Presidential Documents... Determination for the Kingdom of Cambodia Under Section 2(b)(2) of the Export-Import Bank Act of 1945, as... the Export-Import Bank Act of 1945, as amended (12 U.S.C. 635(b)(2)(C)), I hereby determine that...

  19. 75 FR 10667 - Airworthiness Directives; Bombardier, Inc. Model CL-600-2B19 (Regional Jet Series 100 & 440...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-09

    ... Procedures (44 FR 11034, February 26, 1979); and 3. Will not have a significant economic impact, positive or..., Inc. Model CL-600-2B19 (Regional Jet Series 100 & 440) Airplanes AGENCY: Federal Aviation.... Applicability (c) This AD applies to Bombardier, Inc. Model CL-600-2B19 (Regional Jet Series 100 &...

  20. 75 FR 69609 - Airworthiness Directives; Bombardier, Inc. Model CL-600-2B19 (Regional Jet Series 100 & 440...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-15

    ... 12866; 2. Is not a ``significant rule'' under the DOT Regulatory Policies and Procedures (44 FR 11034.... Model CL-600-2B19 (Regional Jet Series 100 & 440) Airplanes AGENCY: Federal Aviation Administration (FAA... Part 2, ``Airworthiness Limitations,'' of the Bombardier CL-600-2B19 Maintenance Requirements...

  1. 76 FR 29997 - Airworthiness Directives; Bombardier, Inc. Model CL-600-2B19 (Regional Jet Series 100 & 440...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-05-24

    ... . SUPPLEMENTARY INFORMATION: Airworthiness Directive 2011-07-06, amendment 39-16643 (76 FR 18024, April 1, 2011.... Model CL-600-2B19 (Regional Jet Series 100 & 440) Airplanes AGENCY: Federal Aviation Administration (FAA.... Model CL-600-2B19 (Regional Jet Series 100 & 440) airplanes. In the AD as published, the reference...

  2. Regulation of development and cancer by the R2B subfamily of RPTPs and the implications of proteolysis

    PubMed Central

    Craig, Sonya E.L.; Brady-Kalnay, Susann M.

    2014-01-01

    The initial cloning of receptor protein tyrosine phosphatases (RPTPs) was met with excitement because of their hypothesized function in counterbalancing receptor tyrosine kinase signaling. In recent years, members of a subfamily of RPTPs with homophilic cell-cell adhesion capabilities, known as the R2B subfamily, have been shown to have functions beyond that of counteracting tyrosine kinase activity, by independently influencing cell signaling in their own right and by regulating cell adhesion. The R2B subfamily is composed of four members: PTPmu (PTPRM), PTPrho (PTPRT), PTPkappa (PTPRK), and PCP-2 (PTPRU). The effects of this small subfamily of RPTPs is far reaching, influencing several developmental processes and cancer. In fact, R2B RPTPs are predicted to be tumor suppressors and are among the most frequently mutated protein tyrosine phosphatases (PTPs) in cancer. Confounding these conclusions are more recent studies suggesting that proteolysis of the full-length R2B RPTPs result in oncogenic extracellular and intracellular protein fragments. This review discusses the current knowledge of the role of R2B RPTPs in development and cancer, with special detail given to the mechanisms and implications that proteolysis has on R2B RPTP function. We also touch upon the concept of exploiting R2B proteolysis to develop cancer imaging tools, and consider the effects of R2B proteolysis on axon guidance, perineural invasion and collective cell migration. PMID:25223585

  3. Modulating effects of acyl-CoA synthetase 5-derived mitochondrial Wnt2B palmitoylation on intestinal Wnt activity

    PubMed Central

    Klaus, Christina; Schneider, Ursula; Hedberg, Christian; Schütz, Anke K; Bernhagen, Jürgen; Waldmann, Herbert; Gassler, Nikolaus; Kaemmerer, Elke

    2014-01-01

    AIM: To investigate the role of acyl-CoA synthetase 5 (ACSL5) activity in Wnt signaling in intestinal surface epithelia. METHODS: Several cell lines were used to investigate the ACSL5-dependent expression and synthesis of Wnt2B, a mitochondrially expressed protein of the Wnt signaling family. Wnt activity was functionally assessed with a luciferase reporter assay. ACSL5-related biochemical Wnt2B modifications were investigated with a modified acyl-exchange assay. The findings from the cell culture models were verified using an Apcmin/+ mouse model as well as normal and neoplastic diseased human intestinal tissues. RESULTS: In the presence of ACSL5, Wnt2B was unable to translocate into the nucleus and was enriched in mitochondria, which was paralleled by a significant decrease in Wnt activity. ACSL5-dependent S-palmitoylation of Wnt2B was identified as a molecular reason for mitochondrial Wnt2B accumulation. In cell culture systems, a strong relation of ACSL5 expression, Wnt2B palmitoylation, and degree of malignancy were found. Using normal mucosa, the association of ACSL5 and Wnt2B was seen, but in intestinal neoplasias the mechanism was only rudimentarily observed. CONCLUSION: ACSL5 mediates antiproliferative activities via Wnt2B palmitoylation with diminished Wnt activity. The molecular pathway is probably relevant for intestinal homeostasis, overwhelmed by other pathways in carcinogenesis. PMID:25356045

  4. 76 FR 65199 - International Conference on Harmonisation; E2B(R3) Electronic Transmission of Individual Case...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-10-20

    ...) Electronic Transmission of Individual Case Safety Reports; Draft Guidance on Implementation; Data Elements... Safety Reports (ICSRs): Implementation Guide--Data Elements and Message Specification'' (the draft E2B(R3... BFC appendix describes the relationship between data elements from the 2001 ICH E2B guidance and...

  5. Anomalous quadrupole feature in the mixed state of YNi2B2C

    NASA Astrophysics Data System (ADS)

    Das, Pradip; Tomy, C. V.; Takeya, H.; Ramakrishnan, S.; Grover, A. K.

    2013-01-01

    We demonstrate the observation of paramagnetic-like anomaly in the mixed state of YNi2B2C crystal from the magnetization measurements for H ∼ 20 kOe. In the LuNi2B2C borocarbide superconductor, observation of such an anomaly was explained on the basis of symmetry reorientation transition of the flux line lattice; i.e., transition from square to triangular lattice due to non-local effects. However, a detailed magnetization study on YNi2B2C sample reveals that such a type of paramagnetic anomaly can arise in the magnetization measurements due to the admixture of a signal from quadrupolar moment with that from dipole moment of the mixed state, if the sample is not positioned precisely at the central position in a VSM coil. When we intentionally shifted the sample position from the centering position to preferentially record the quadrupole moment only, we noted that the merging of the forward and the reverse legs of the loop near the superconductor-normal boundary is much better defined in the Q-H measurements, rather than in the M-H measurements. The Q-H plots, thus, provide a more accurate recipe to determine the Hc2 values. We have also examined the timescale disorder experienced by the flux line lattice (FLL) during the field ramping process in isothermal M-H measurements. Our study revealed the existence of non-monotonic dependence of spatial disorder within FLL due to the change in the ramp rate. The field ramp rate acts as an additional source of disorder in the formation of the FLL.

  6. Calcium sensitivity and myofilament lattice structure in titin N2B KO mice

    PubMed Central

    Lee, Eun-Jeong; Nedrud, Joshua; Schemmel, Peter; Gotthardt, Michael; Irving, Thomas C.; Granzier, Henk L

    2012-01-01

    The cellular basis of the Frank-Starling “Law of the Heart” is the length-dependence of activation, but the mechanisms by which the sarcomere detects length changes and converts this information to altered calcium sensitivity has remained elusive. Here the effect of titin-based passive tension on the length-dependence of activation (LDA) was studied by measuring the tension-pCa relation in skinned mouse LV muscle at two sarcomere lengths (SLs). N2B KO myocardium, where the N2B spring element in titin is deleted and passive tension is elevated, was compared to WT myocardium. Myofilament lattice structure was studied with low-angle X-ray diffraction; the myofilament lattice spacing (d10) was measured as well as the ratio of the intensities of the 1,1 and 1,0 diffraction peaks (I11/I10) as an estimate of the degree of association of myosin heads with the thin filaments. Experiments were carried out in skinned muscle in which the lattice spacing was reduced with Dextran-T500. Experiments with and without lattice compression were also carried out following PKA phosphorylation of the skinned muscle. Under all conditions that were tested, LDA was significantly larger in N2B KO myocardium compared to WT myocardium, with the largest differences following PKA phosphorylation. A positive correlation between passive tension and LDA was found that persisted when the myofilament lattice was compressed with Dextran and that was enhanced following PKA phosphorylation. Low-angle X-ray diffraction revealed a shift in mass from thin filaments to thick filaments as sarcomere length was increased. Furthermore, a positive correlation was obtained between myofilament lattice spacing and passive tension and the change in I11/I10 and passive tension and these provide possible explanations for how titin-based passive tension might regulate calcium sensitivity. PMID:23246787

  7. ON THE APPARENT ORBITAL INCLINATION CHANGE OF THE EXTRASOLAR TRANSITING PLANET TrES-2b

    SciTech Connect

    Scuderi, Louis J.; Dittmann, Jason A.; Males, Jared R.; Green, Elizabeth M.; Close, Laird M.

    2010-05-01

    On 2009 June 15 UT the transit of TrES-2b was detected using the University of Arizona's 1.55 m Kuiper Telescope with 2.0-2.5 millimag rms accuracy in the I band. We find a central transit time of T{sub c} = 2454997.76286 {+-} 0.00035 HJD, an orbital period of P = 2.4706127 {+-} 0.0000009 days, and an inclination angle of i = 83.{sup 0}92 {+-} 0{sup 0}.05, which is consistent with our re-fit of the original I-band light curve of O'Donovan et al. where we find i = 83.{sup 0}84 {+-} 0{sup 0}.05. We calculate an insignificant inclination change of {Delta}i = -0.{sup 0}08 {+-} 0{sup 0}.07 over the last three years, and as such, our observations rule out, at the {approx}11{sigma} level, the apparent change of orbital inclination to i{sub predicted} = 83.{sup 0}35 {+-} 0{sup 0}.1 as predicted by Mislis and Schmitt and Mislis et al. for our epoch. Moreover, our analysis of a recently published Kepler Space Telescope light curve for TrES-2b finds an inclination of i = 83.{sup 0}91 {+-} 0.{sup 0}03 for a similar epoch. These Kepler results definitively rule out change in i as a function of time. Indeed, we detect no significant changes in any of the orbital parameters of TrES-2b.

  8. E-hubs: the new B2B (business-to-business) marketplaces.

    PubMed

    Kaplan, S; Sawhney, M

    2000-01-01

    Electronic hubs--Internet-based intermediaries that host electronic marketplaces and mediate transactions among businesses--are generating a lot of interest. Companies like Ariba, Chemdex, and Commerce One have already attained breathtaking stock market capitalizations. Venture capitalists are pouring money into more business-to-business start-ups. Even industrial stalwarts like GM and Ford are making plans to set up their own Web markets. As new entrants with new business models pour into the business-to-business space, it's increasingly difficult to make sense of the landscape. This article provides a blueprint of the e-hub arena. The authors start by looking at the two dimensions of purchasing: what businesses buy--manufacturing inputs or operating inputs--and how they buy--through systematic sourcing or spot sourcing. They classify B2B e-hubs into four categories: MRO hubs, yield managers, exchanges, and catalog hubs, and they discuss each type in detail. Drilling deeper into this B2B matrix, the authors look at how e-hubs create value--through aggregation and matching--and explain when each mechanism works best. They also examine the biases of e-hubs. Although many e-hubs are neutral--they're operated by independent third parties--some favor the buyers or sellers. The authors explain the differences and discuss the pros and cons of each position. The B2B marketplace is changing rapidly. This framework helps buyers, sellers, and market makers navigate the landscape by explaining what the different hubs do and how they add the most value. PMID:11183982

  9. HATS-2b: A transiting extrasolar planet orbiting a K-type star showing starspot activity

    NASA Astrophysics Data System (ADS)

    Mohler-Fischer, M.; Mancini, L.; Hartman, J. D.; Bakos, G. Á.; Penev, K.; Bayliss, D.; Jordán, A.; Csubry, Z.; Zhou, G.; Rabus, M.; Nikolov, N.; Brahm, R.; Espinoza, N.; Buchhave, L. A.; Béky, B.; Suc, V.; Csák, B.; Henning, T.; Wright, D. J.; Tinney, C. G.; Addison, B. C.; Schmidt, B.; Noyes, R. W.; Papp, I.; Lázár, J.; Sári, P.; Conroy, P.

    2013-10-01

    We report the discovery of HATS-2b, the second transiting extrasolar planet detected by the HATSouth survey. HATS-2b is moving on a circular orbit around a V = 13.6 mag, K-type dwarf star (GSC 6665-00236), at a separation of 0.0230 ± 0.0003 AU and with a period of 1.3541 days. The planetary parameters have been robustly determined using a simultaneous fit of the HATSouth, MPG/ESO 2.2 m/GROND, Faulkes Telescope South/Spectral transit photometry, and MPG/ESO 2.2 m/FEROS, Euler 1.2 m/CORALIE, AAT 3.9 m/CYCLOPS radial-velocity measurements. HATS-2b has a mass of 1.37 ± 0.16 MJ, a radius of 1.14 ± 0.03 RJ, and an equilibrium temperature of 1567 ± 30 K. The host star has a mass of 0.88 ± 0.04 M⊙ and a radius of 0.89 ± 0.02 R⊙, and it shows starspot activity. We characterized the stellar activity by analyzing two photometric follow-up transit light curves taken with the GROND instrument, both obtained simultaneously in four optical bands (covering the wavelength range of 3860-9520 Å). The two light curves contain anomalies compatible with starspots on the photosphere of the host star along the same transit chord. Tables of the individual photometric measurements are only available at the CDS via anonymous ftp to http://cdsarc.u-strasbg.fr (ftp://130.79.128.5) or via http://cdsarc.u-strasbg.fr/viz-bin/qcat?J/A+A/558/A55

  10. The Preparation and Characterization of INTEC Phase 2b Composition Variation Study Glasses

    SciTech Connect

    B. A. Staples; B. A. Scholes; L. L. Torres; C. A. Musick; B. R. Boyle; D. K. Peeler; J. D. Vienna

    2000-02-01

    The second phase of the composition variation study (CVS) for the development of glass compositions to immobilize Idaho Nuclear Technology and Engineering Center (INTEC) high level wastes (HLW) is complete. This phase of the CVS addressed waste composition of high activity waste fractions (HAW) from the initial separations flowsheet. Updated estimates if INTEC calcined HLW compositions and of high activity waste fractions proposed to be separated from dissolved calcine were used as the waste component for this CVS phase. These wastes are of particular interest because high aluminum, calcium, zirconium, fluorine, potassium, and low iron and sodium content places them outside the vitrification experience in the Department of Energy complex. Because of the presence of calcium and fluorine, two major zirconia calcine components not addressed in Phase I, a series of scooping tests, designated Phase 2a, were performed. The results of these tests provided information on the effects of calcium and fluoride solubility and their impacts on product properties and composition boundary information for Phase 2b. Details and results of Phase 2a are reported separately. Through application of statistical techniques and the results of Phase 2a, a test matrix was defined for Phase 2b of the CVS. From this matrix, formulations were systematically selected for preparation and characterization with respect to visual and optical homogeneity, viscosity as a function of melt temperature, liquidus temperature (TL), and leaching properties based on response to the product consistency test. The results of preparing and characterizing the Phase 2b glasses are presented in this document. Based on the results, several formulations investigated have suitable properties for further development. A full analysis of the composition-product characteristic relationship of glasses being developed for immobilizing INTEC wastes will be performed at the completion of composition-property relationship

  11. Macroscale production and analysis of crystalline interferon alpha-2B in microgravity on STS-52

    NASA Astrophysics Data System (ADS)

    Reichert, Paul; Nagabhushan, Tattanahalli L.; Long, Marianna M.; Bugg, Charles E.; DeLucas, Lawrence J.

    1996-03-01

    The development and production of a zinc-interferon alpha-2b crystalline suspension on STS-52 has accelerated our ability to prepare novel high quality pharmaceutical preparations. Crystalline suspensions of protein therapeutics have applications in drug delivery, formulation, and manufacturing. These applications require crystalline suspensions of relatively small particles (<100 microns) of uniform size and shape. Previously, a crystalline form of interferon alpha-2b was identified from microscale crystallization methods with utility in pharmaceutical applications from microscale crystallization methods. Conditions for macroscale crystallization were established by adapting a microscale vapor diffusion method to a macroscale temperature induction method. A series of earth based pilot experiments established conditions to reproducibly crystallize zinc interferon alpha-2b in high yield and under ``cleanroom'' conditions. These conditions were maintained in microgravity. Greater than 95% of the available protein crystallized in both the ground and flight experiments. The samples were analyzed using a battery of physical, biochemical, and biological characterization methods. The results demonstrated that sample processing, polysulfone bottle confinement, and the conditions used for crystallization did not have a negative effect on protein integrity. Redissolved crystals from the flight and ground experiments showed full biological activity in a cytopathic effect inhibition assay as compared to an interferon control standard. Morphometric analysis comparing the overall length and width of the derived crystals showed a 2.4 fold increase in the length and width of the space grown crystals as compared to earth grown crystals. Subcutaneous injections of space grown crystalline preparation was compared to a non-crystalline interferon preparation in a primate pharmacokinetic study. The crystalline interferon preparation had a measured serum half-life of 12 hours as compared

  12. Acquired von Willebrand syndrome with a type 2B phenotype: diagnostic and therapeutic dilemmas.

    PubMed

    Scepansky, Ellen; Othman, Maha; Smith, Hedy

    2014-01-01

    In this report, we provide evidence of an acquired von Willebrand syndrome (AVWS) with a type 2B phenotype rather than the expected type 1 or 2A. The patient was referred prior to surgical removal of a fibrous mass within the maxillary sinus. His first bleeding 7 years earlier following a retinal tear had been complicated by monocular blindness. Several mucocutanous bleedings followed. Hematological investigations revealed von Willebrand factor (VWF):Ag 91 IU/ml, factor VIII 86 IU/ml, VWF:RCo 34 IU/ml and profound thrombocytopenia with platelet clumping. VWF multimer analysis showed a loss of high-molecular-weight multimers and his plasma aggregated normal platelets under low ristocetin concentration, consistent with type 2B von Willebrand disease (VWD). Sequencing of VWF exon 28 and of the platelet GP1BA gene to investigate the possibility of platelet-type VWD failed to reveal mutations. Serum protein electrophoresis showed a monoclonal IgG protein and led to the diagnosis of monoclonal gammopathy of unknown significance (MGUS), raising suspicion of an AVWS. Over 2 years, he experienced severe gingival bleedings and traumatic intracerebral hemorrhage. Following debridement of the sinus mass, the patient required 20 units of packed red blood cells, despite high-dose Humate-P, continuous Amicar and twice-daily platelet transfusions. Bleeding finally ceased following infusion of activated factor VIIa. A history of prior uncomplicated vasectomy and tendon laceration, no family history of bleeding, the inability to identify a causative mutation in either exon 28 VWF or platelet GP1BA and the MGUS led to diagnosis of AVWS with a type 2B phenotype. This case highlights the difficulties in assigning a diagnosis and the management of bleeding in a patient with an atypical presentation of AVWS. PMID:24296552

  13. Spectral analysis of Cu(2+): B(2)O(3)--ZnO--PbO glasses.

    PubMed

    Lakshminarayana, G; Buddhudu, S

    2005-11-01

    A new series of heavy metal oxide (PbO) based zinc borate glasses in the chemical composition of (95-x)B(2)O(3)-5ZnO-xPbO (x=10, 15, 20, 25, 30, 35, 40, 45 and 50 mol%) have been prepared to verify their UV filtering performance. Both direct and indirect optical band gaps (E(opt)) have been evaluated for these glasses. For a reference glass of 45B(2)O(3)-5ZnO-50PbO, refractive indices at different wavelengths are measured and found the results satisfactorily correlated with the theoretical data upon the computation of Cauchy's constants of A=1.766029949, B=159531.024 nm(2) and C=-1.078 x 10(10) nm(4). Measurements concerning X-ray diffraction (XRD), FT-IR, differential scanning colorimeter (DSC) profiles have been carried out for this glass. The FT-IR profile has revealed that the glass has both BO(3) and BO(4) units. From DSC thermogram, glass transition temperature (T(g)), crystallization temperature (T(c)) and melting temperature (T(m)) have been located and from them, other related parameters of the glass have also been calculated. Visible absorption spectra of 45B(2)O(3)-5ZnO-(50-x)PbO-xCuO (x=0. 1, 0.2, 0.5 and 1.0 mol%) have revealed two absorption bands at around 400 nm ((2)B(1g)-->(2)E(g)) and 780 nm ((2)B(1g)-->(2)B(2g)) of Cu(2+) ions, respectively. Emission bands at 422 and 512 nm are found for the 1 mol % CuO doped glass with excitations at 306 and 332 nm. PMID:16257737

  14. Darwin, Engels und die Rolle der Arbeit in der biologischen und kulturellen Evolution des Menschen

    NASA Astrophysics Data System (ADS)

    Reichholf, Josef H.

    Im Jahre 1876, 5 Jahre nach Erscheinen von Darwins Buch über die Evolution des Menschen und die sexuelle Selektion (Darwin 1871), veröffentlichte Friedrich Engels den berühmt gewordenen Essay "Anteil der Arbeit an der Menschwerdung des Affen“ (Engels 1876). Die Kernfrage darin lautet in Kurzform: Warum hat der Mensch eigentlich ein Bedürfnis nach Arbeit? Engels Antwort wird nachfolgend näher betrachtet und vom gegenwärtigen Kenntnisstand aus beurteilt. Wie sich zeigen wird, beantworten seine Überlegungen die Frage nicht wirklich. Sie ist weiterhin offen. Es können lediglich einige zusätzliche Anhaltspunkte zur Diskussion gestellt werden. Angesichts des drängenden Problems millionenfacher Arbeitslosigkeit und der Forderungen nach einem "Grundrecht auf Arbeit“ kommt den Überlegungen zum möglichen Ursprung des Bedürfnisses nach Arbeit mehr als nur akademisches Interesse zu.

  15. Electronic structure and vibrational properties of KRbAl{sub 2}B{sub 2}O{sub 7}

    SciTech Connect

    Atuchin, V.V.; Adichtchev, S.V.; Bazarov, B.G.; Bazarova, Zh.G.; Gavrilova, T.A.; Grossman, V.G.; Kesler, V.G.; Meng, G.S.; Lin, Z.S.; Surovtsev, N.V.

    2013-03-15

    Graphical abstract: With the KRbAl{sub 2}B{sub 2}O{sub 7} powder formed by solid state synthesis (left), Raman spectrum (right upper) and XPS valence electronic states (right lower) were measured, agreed with the first-principles results. Highlights: ► KRbAl{sub 2}B{sub 2}O{sub 7} powder was obtained by solid state synthesis. ► Vibrational properties of KRbAl{sub 2}B{sub 2}O{sub 7} were determined by unpolarized Raman spectrum. ► Electronic structures of KRbAl{sub 2}B{sub 2}O{sub 7} were measured by XPS. ► Experimental electronic structure is consistent with the first-principles result. ► KRbAl{sub 2}B{sub 2}O{sub 7} has a noticeable refractive indices increase and small NLO effects decrease compared to K{sub 2}Al{sub 2}B{sub 2}O{sub 7}. - Abstract: The physical properties of KRbAl{sub 2}B{sub 2}O{sub 7} have been considered in comparison with those of K{sub 2}Al{sub 2}B{sub 2}O{sub 7} and Rb{sub 2}Al{sub 2}B{sub 2}O{sub 7}. The vibrational parameters of KRbAl{sub 2}B{sub 2}O{sub 7} have been measured by Raman spectroscopy as very similar to those of K{sub 2}Al{sub 2}B{sub 2}O{sub 7}. The electronic structures of KRbAl{sub 2}B{sub 2}O{sub 7} have been evaluated by X-ray photoelectron spectroscopy and ab initio computations using CASTEP package. A noticeable refractive indices increase and small decrease of nonlinear optical properties have been found in KRbAl{sub 2}B{sub 2}O{sub 7} in reference to optical parameters of K{sub 2}Al{sub 2}B{sub 2}O{sub 7}.

  16. Haptische Modellierung und Deformation einer Kugelzelle

    NASA Astrophysics Data System (ADS)

    Schippritt, Darius; Wiemann, Martin; Lipinski, Hans-Gerd

    Haptische Simulationsmodelle dienen in der Medizin in erster Linie dem Training operativer Eingriffe. Sie basieren zumeist auf physikalischen Gewebemodellen, welche eine sehr genaue Simulation der biomechanischen Eigenschaften des betreffenden Gewebes erlauben, aber gleichzeitig sehr rechenintensiv und damit zeitaufwändig in der Ausführung sind. Die menschliche Wahrnehmung kann allerdings auch eine ungenaue haptische Modellierung psychooptisch ausgleichen. Daher kann es sinnvoll sein, haptische Simulationen auch mit nicht vollständig physikalisch definierten Deformationsmodellen durchzuführen. Am Beispiel der haptischer Simulation einer in-vitro Fertilisation wird gezeigt, dass durch die Anwendung eines geometrischen Deformationsmodells eine künstliche Befruchtung unter realistischen experimentellen Bedingungen in Echtzeit haptisch simuliert und damit trainiert werden kann.

  17. Newtons Principia Mathematica Philosophia und Plancks Elementarkonstanten

    NASA Astrophysics Data System (ADS)

    Rompe, R.; Treder, H.-J.

    Die Newtonschen Prinzipien, zusammen mit den Planckschen Elementarkonstanten, erweisen sich als gesichertes Fundament der Physik und der exakten Wissenschaften aller Richtungen.Der Begriffsfundus der Physik ist ausreichend für alle physikalischen aber auch weiterreichenden Probleme anderer Naturwissenschaften und Technik. Es zeigt sich, daß die klassische Physik von vornherein so angelegt wurde, daß sie über die Physik der makroskopischen Körper weit hinaus-greifen kann.Translated AbstractNewton's Principia Mathematica Philosophia and Planck's Elementary ConstantsTogether with Planck's elementary constants Newton's principles prove a guaranteed basis of physics and exact sciences of all directions.The conceptions in physics are competent at all physical problems as well as technology too. Classical physics was founded in such a way to reach far beyond the physics of macroscopic bodies.

  18. Biochips und ihr Einsatz in der Lebensmittelanalytik

    NASA Astrophysics Data System (ADS)

    Huber, Ingrid; Zeltz, Patric

    Mit der Verbreitung des Begriffes "Biochip“ in den biotechnologischen Medien wurde Ende der 1990er-Jahre zunächst der Eindruck erweckt, dass die Computerelektronik in die molekularbiologischen Anwendungen eingestiegen ist [18]. In nur wenigen Jahren hat sich die Biochiptechnologie zu einem Verfahren entwickelt, das aus der molekularbiologischen Grundlagenforschung nicht mehr wegzudenken ist und über eine Vielzahl von Einsatzbereichen verfügt. Die Biochiptechnologie ermöglicht die Miniaturisierung von DNA-, RNA- bzw. Proteinanalytik in hochparallelen Formaten. Dieser hohe Parallelisierungsgrad ist einer der wesentlichen Vorteile dieser Technik gegenüber klassischen molekularbiologischen Methoden. Sie wird heutzutage vor allem in der Genomforschung eingesetzt, für Genexpressionsstudien, zum Screening von single nucleotide polymorphisms (SNPs), in der pharmakogenetischen Forschung sowie in der Erforschung von Erbkrankheiten und in der Krebsforschung [1, 7, 19]. Neben vielen weiteren Bereichen finden Biochips auch spezielle Anwendungen in der Lebensmittelanalytik.

  19. Pockel's electro-optic coefficients of lithium tetraborate Li2B4O7

    NASA Astrophysics Data System (ADS)

    Méndez, A.; García-Cabañes, A.; Diéguez, E.; Cabrera, J. M.

    1999-08-01

    Pockel's electro-optic coefficients r31 and r33 of Li2B4O7 have been measured with an improved interferometric (Mach-Zehnder) method. The effective rc coefficient has also been measured by a polarimetric setup which, within the experimental error, has given the same value as that of the interferometric method. Attempts to measure the r42 coefficient with either the interferometric or the polarimetric method have given a value below the detection limit of our setups. All coefficients are given in terms of the published values of the piezoelectric coefficient d13.

  20. PON2 and ATP2B2 gene polymorphisms with noise-induced hearing loss

    PubMed Central

    Li, Xiuting; Cao, Jinglian; Wang, Jun; Song, Haiyan; Ji, Guixiang; Dong, Qiu; Wei, Chunlong; Cao, Ying; Wang, Boshen

    2016-01-01

    Background Noise-induced hearing loss (NIHL) is a complex disease induced by a combination of genetic and environmental factors. Paraoxonase2 (PON2) gene involved in the regulation of reactive oxygen species, and affecting the vulnerability of cochlea to NIHL, and ATPase, calcium-transporting, plasma membrane 2 (ATP2B2) gene which encodes plasma membrane calcium-transporting ATPase isoform 2 (PMCA2) are the candidate genes relating to the attack of NIHL. In this study, we investigated whether ATP2B2 and PON2 polymorphisms were associated with NIHL in Chinese of Han nationality population. Methods We performed a case-control study between six single nucleotide polymorphisms (SNPs) (rs1719571, rs3209637 and rs4327369 within ATP2B2, rs12026, rs7785846 and rs12704796 within PON2) and NIHL in 454 subjects. All the SNPs were genotypes, using the TaqMan MGB probe assay. Odds ratios (ORs) were calculated with 95% confidence intervals (95% CIs) with logistic regression analysis to test the level of association for SNPs. Results In our study, 221 subjects with hearing loss and 233 subjects without hearing loss were recruited. The frequencies of the CG and CG + GG genotype of rs12026 (PON2) conferred risk factors for NIHL with adjusted OR values of 2.62 (95% CI, 1.69–4.06) and 2.48 (95% CI, 1.63–3.78), respectively. This kind of significance was also found at locus rs7785846, where genotypes CT and CT + TT were the risk types, with adjusted ORs of 2.52 (95% CI, 1.62–3.93) and 2.35 (95% CI, 1.54–3.58), respectively. We performed stratified analysis per noise exposure level, when it came to rs7785846 and rs12026 in the >92 dB(A) noise exposure group, the subjects who carried heterozygote were of significantly (P<0.01) higher susceptibility to NIHL than homozygote carriers. By contrast, no significantly higher risk was found for any rs12704796 genotypes or any genotypes in ATP2B2 (P>0.05), which may suggest that these SNPs did not have significant effects on noise

  1. Impact of UGT2B17 gene deletion on the steroid profile of an athlete.

    PubMed

    Martín-Escudero, Pilar; Muñoz-Guerra, Jesús; Del Prado, Nayade; Galindo Canales, Mercedes; Fuentes Ferrer, Manuel; Vargas, Soledad; Soldevilla, Ana B; Serrano-Garde, Ester; Miguel-Tobal, Francisco; Maestro de Las Casas, Marisa; Fernandez-Pérez, Cristina

    2015-12-01

    The measurement of the testosterone to epitestosterone ratio (T/E ratio) in urine is often used as a marker for testosterone administration in the doping control field. This study examines the frequencies of the different expression forms of the UGT2B17 gene, and assesses their effects on this marker in volunteer subjects. The sample for this descriptive study was composed of male and female athletes aged between 16 and 55 years old who practiced different sports disciplines. All participants underwent a sports-medical physical examination, and subsequently provided 10 urine samples consecutively over a period of 48 h. The dependent variable examined was T/E and the main independent variable was the UGT2B17 gene polymorphism. During 1 year, 1410 urine samples were obtained from 141 athletes. The frequencies of the three genotypes were as follows: wt homozygotes (ins/ins) 48.2% (n = 68), mutant homozygotes (del/del) 12.1% (n = 17), and heterozygotes (ins/del) 39.7% (n = 56). Genotype distributions varied significantly (P < 0.001) according to ethnicity, 80% of Asian subjects being homozygous for the gene deletion (del/del) compared to 6.9% of Caucasian subjects. A multivariate analysis adjusted for genotype, age, sex, and sports discipline revealed that athletes with the del/del polymorphism showed a significantly lower mean T/E than heterozygotes (ins/del). In contrast, homozygous athletes for the gene insertion (ins/ins) showed higher mean T/E ratios than heterozygotes (ins/del). UGT2B17 gene deletion has a strong influence on the T/E ratio in urine, which is the most efficient indicator of testosterone prohormone misuse. Others factors studied seem not to have such an impact. The genotyping of UGT2B17 is an important source of information for understanding steroid profiling in the doping control field; therefore it is suggested that it be included in the Athletes Biological Passport. PMID:26668303

  2. The Amazon Boundary-Layer Experiment (ABLE 2B) - A meteorological perspective

    NASA Technical Reports Server (NTRS)

    Garstang, Michael; Greco, Steven; Scala, John; Swap, Robert; Ulanski, Stanley; Fitzjarrald, David; Martin, David; Browell, Edward; Shipman, Mark; Connors, Vickie

    1990-01-01

    The Amazon Boundary-Layer Experiments (ABLE) 2A and 2B, which were performed near Manaus, Brazil in July-August, 1985, and April-May, 1987 are discussed. The experiments were performed to study the sources, sinks, concentrations, and transports of trace gases and aerosols in rain forest soils, wetlands, and vegetation. Consideration is given the design and preliminary results of the experiment, focusing on the relationships between meteorological scales of motion and the flux, transports, and reactions of chemical species and aerosols embedded in the atmospheric fluid. Meteorological results are presented and the role of the meteorological results in the atmospheric chemistry experiment is examined.

  3. Exfoliation Corrosion Behavior of 2B06 Aluminum Alloy in a Tropical Marine Atmosphere

    NASA Astrophysics Data System (ADS)

    Cui, Z. Y.; Li, X. G.; Xiao, K.; Dong, C. F.; Wang, L. W.; Zhang, D. W.; Liu, Z. Y.

    2015-01-01

    In this study, corrosion behavior of 2B06 aluminum alloy was investigated after exposure to a tropical marine atmosphere for up to 4 years. After 6 months, the specimen showed exfoliation corrosion as well as rapid increase in thickness loss and corrosion rate. Exfoliation corrosion was found to initiate from hydrogen-assisted intergranular cracks and propagate extensively due to the wedge effect of the corrosion products. During the exposure test, corrosion on the groundward surface was considerably more severe than that on the skyward surface, which could be attributed to the different exposure conditions on the two surfaces.

  4. A comprehensive clinical research database based on CDISC ODM and i2b2.

    PubMed

    Meineke, Frank A; Stäubert, Sebastian; Löbe, Matthias; Winter, Alfred

    2014-01-01

    We present a working approach for a clinical research database as part of an archival information system. The CDISC ODM standard is target for clinical study and research relevant routine data, thus decoupling the data ingest process from the access layer. The presented research database is comprehensive as it covers annotating, mapping and curation of poorly annotated source data. Besides a conventional relational database the medical data warehouse i2b2 serves as main frontend for end-users. The system we developed is suitable to support patient recruitment, cohort identification and quality assurance in daily routine. PMID:25160362

  5. Photothermal Investigation of Surface Defects of Pure Semiconducting A2B6 Materials

    NASA Astrophysics Data System (ADS)

    Zakrzewski, J.; Maliński, M.; Strzałkowski, K.; Madaj, D.; Firszt, F.; Łęgowski, S.; Męczyńska, H.

    2012-04-01

    Photoacoustic spectroscopy is a sensitive and useful method to investigate the quality of semiconducting A2B6 crystals. An imperfection of surface quality can strongly influence photoacoustic spectra but it shows the different character for the different kinds of semiconducting materials. To properly interpret the amplitude and phase spectra, the temperature distribution and its modifications, due to the surface defects, are needed. The Blonskij model of the temperature distribution was used to investigate the influence of the defect on the amplitude and phase spectra.

  6. Synthesis and fluorosolvatochromism of 3-arylnaphtho[1,2-b]quinolizinium derivatives

    PubMed Central

    Pithan, Phil M; Decker, David; Sardo, Manlio Sutero; Viola, Giampietro

    2016-01-01

    Summary Cationic biaryl derivatives were synthesized by Suzuki–Miyaura coupling of 3-bromonaphtho[1,2-b]quinolizinium bromide with arylboronic acids. The resulting cationic biaryl derivatives exhibit pronounced fluorosolvatochromic properties. First photophysical studies in different solvents showed that the emission energy of the biaryl derivatives decreases with increasing solvent polarity. This red-shifted emission in polar solvents is explained by a charge shift (CS) in the excited state and subsequent solvent relaxation. Furthermore, the polarity of protic polar and aprotic polar solvents affects the emission energy to different extent, which indicates a major influence of hydrogen bonding on the stabilization of the ground and excited states. PMID:27340476

  7. Synthesis and optical properties of polycrystalline Li2Al2B2O7 (LABO)

    NASA Astrophysics Data System (ADS)

    Dagdale, S. R.; Muley, G. G.

    2016-05-01

    A polycrystalline lithium aluminum borate (Li2Al2B2O7, LABO) has been synthesized by using simple solid-state technique. The obtained LABO polycrystalline was characterized by powder X-ray diffraction; Fourier transform infrared (FT-IR) spectroscopy and second harmonic generation (SHG) efficiency measurement. The functional groups were identified using the FT-IR spectroscopic data. The SHG efficiency of the polycrystalline material was obtained by the classic Kurtz powder technique using a fundamental wavelength 1064 nm of Nd:YAG laser and it is found to be 1.4 times that of potassium dihydrogen phosphate (KDP).

  8. High Energy Ion Beam Combustion Of TiO{sub 2}-B-Al Mixture

    SciTech Connect

    Rahbari, R. G.; Hamdi, M.; Yahya, R.; Yap, S. L.; Ngoi, S. K.; Wong, C. S.; Leong, L.

    2009-07-07

    High energy ion beam of a plasma focus device was used to combust TiO{sub 2}-B-Al powder mixture under quasi-adiabatic conditions. Despite uncompleted propagation of combustion wave through the sample, the microstructure of the product was completely different from that obtained from conventional bulk heating in furnace. Combustion reaction of the mixture in furnace at 700 deg. C resulted in spiral-helix motion, while plasma synthesis of the same mixture resulted in uniform self-sustaining wave propagation.

  9. Common Variants in the ATP2B1 Gene Are Associated With Susceptibility to Hypertension

    PubMed Central

    Tabara, Yasuharu; Kohara, Katsuhiko; Kita, Yoshikuni; Hirawa, Nobuhito; Katsuya, Tomohiro; Ohkubo, Takayoshi; Hiura, Yumiko; Tajima, Atsushi; Morisaki, Takayuki; Miyata, Toshiyuki; Nakayama, Tomohiro; Takashima, Naoyuki; Nakura, Jun; Kawamoto, Ryuichi; Takahashi, Norio; Hata, Akira; Soma, Masayoshi; Imai, Yutaka; Kokubo, Yoshihiro; Okamura, Tomonori; Tomoike, Hitonobu; Iwai, Naoharu; Ogihara, Toshio; Inoue, Itsuro; Tokunaga, Katsushi; Johnson, Toby; Caulfield, Mark; Munroe, Patricia; Umemura, Satoshi; Ueshima, Hirotsugu; Miki, Tetsuro

    2016-01-01

    Hypertension is one of the most common complex genetic disorders. We have described previously 38 single nucleotide polymorphisms (SNPs) with suggestive association with hypertension in Japanese individuals. In this study we extend our previous findings by analyzing a large sample of Japanese individuals (n=14 105) for the most associated SNPs. We also conducted replication analyses in Japanese of susceptibility loci for hypertension identified recently from genome-wide association studies of European ancestries. Association analysis revealed significant association of the ATP2B1 rs2070759 polymorphism with hypertension (P=5.3×10−5; allelic odds ratio: 1.17 [95% CI: 1.09 to 1.26]). Additional SNPs in ATP2B1 were subsequently genotyped, and the most significant association was with rs11105378 (odds ratio: 1.31 [95% CI: 1.21 to 1.42]; P=4.1×10−11). Association of rs11105378 with hypertension was cross-validated by replication analysis with the Global Blood Pressure Genetics consortium data set (odds ratio: 1.13 [95% CI: 1.05 to 1.21]; P=5.9×10−4). Mean adjusted systolic blood pressure was highly significantly associated with the same SNP in a meta-analysis with individuals of European descent (P=1.4×10−18). ATP2B1 mRNA expression levels in umbilical artery smooth muscle cells were found to be significantly different among rs11105378 genotypes. Seven SNPs discovered in published genome-wide association studies were also genotyped in the Japanese population. In the combined analysis with replicated 3 genes, FGF5 rs1458038, CYP17A1, rs1004467, and CSK rs1378942, odds ratio of the highest risk group was 2.27 (95% CI: 1.65 to 3.12; P=4.6×10−7) compared with the lower risk group. In summary, this study confirmed common genetic variation in ATP2B1, as well as FGF5, CYP17A1, and CSK, to be associated with blood pressure levels and risk of hypertension. PMID:20921432

  10. TMI-2 B-loop steam generator tube sheet loose debris examination and analysis

    SciTech Connect

    Hayner, G O; Hardt, T L

    1989-06-01

    The debris recovered from the upper tube sheet of the TMI-2-B-loop steam generator was analyzed in an effort to determine the concentration and distribution of the chemical and radiochemical species. The debris is of special interest because it is believed to have been transported from the core region sequence between 174 and 192 min after accident initiation when a B-loop reactor coolant pump was restarted. Characterization of five size fractions and 10 of the largest particles was accomplished by destructive (chemical, radiochemical, metallography, and SEM/EDS) and nondestructive (photographic examination and density) methods of analysis. 2 refs., 7 figs., 14 tabs.

  11. Synthesis and fluorosolvatochromism of 3-arylnaphtho[1,2-b]quinolizinium derivatives.

    PubMed

    Pithan, Phil M; Decker, David; Sardo, Manlio Sutero; Viola, Giampietro; Ihmels, Heiko

    2016-01-01

    Cationic biaryl derivatives were synthesized by Suzuki-Miyaura coupling of 3-bromonaphtho[1,2-b]quinolizinium bromide with arylboronic acids. The resulting cationic biaryl derivatives exhibit pronounced fluorosolvatochromic properties. First photophysical studies in different solvents showed that the emission energy of the biaryl derivatives decreases with increasing solvent polarity. This red-shifted emission in polar solvents is explained by a charge shift (CS) in the excited state and subsequent solvent relaxation. Furthermore, the polarity of protic polar and aprotic polar solvents affects the emission energy to different extent, which indicates a major influence of hydrogen bonding on the stabilization of the ground and excited states. PMID:27340476

  12. Mol-Gastronomie Vinaigrettes und Benetzung

    NASA Astrophysics Data System (ADS)

    Vilgis, Thomas

    2005-03-01

    Dass wir Salatblätter mit einer Vinaigrette übergießen, hat natürlich einen kulinarischen Grund: Die Kombination von Essig und Öl verleiht Salat erheblich an Geschmack. Nicht nur durch deren Eigengeschmack, sondern auch durch die Lösungseigenschaften von Geschmacksstoffen. Allerdings liefern Salatsaucen auch einen physikalischen Grund für ihre Beliebtheit: die Benetzungsfähigkeit der Blätter.

  13. MAD2B-mediated SnoN downregulation is implicated in fibroblast activation and tubulointerstitial fibrosis.

    PubMed

    Tang, Hui; Su, Hua; Fan, Di; Ye, Chen; Lei, Chun-Tao; Jiang, Hua-Jun; Gao, Pan; He, Fang-Fang; Zhang, Chun

    2016-07-01

    MAD2B, an anaphase-promoting complex/cyclosome (APC/C) inhibitor and a small subunit of DNA polymerase ζ, is indispensible for mitotic checkpoint control and DNA repair. Previously, we established that MAD2B is expressed in glomerular and tubulointerstitial compartments and participates in high glucose-induced podocyte injury. However, its role in other renal diseases remains elusive. In the present study, we aim to illustrate the potential role of MAD2B in the pathogenesis of renal fibrosis. By immunofluorescence and Western blotting, we found MAD2B expression is obviously increased in tubulointerstitial fibrosis (TIF) patients and unilateral ureteral obstruction (UUO) mice. It is widely accepted that resident fibroblasts are the major source of collagen-producing myofibroblasts during TIF. Therefore, we evaluated the level of MAD2B in fibroblasts (NRK-49F) exposed to transforming growth factor (TGF)-β1 by immunoblotting and revealed that MAD2B is upregulated in a time-dependent manner. Intriguingly, SnoN, a transcriptional repressor of the TGF-β1/Smad signaling pathway, is decreased in TGF-β1-treated fibroblasts as well as the kidney cortex from TIF patients and UUO mice. Either in vitro or in vivo, local genetic depletion of MAD2B by lentiviral transfection could preserve SnoN abundance and suppress Smad3 phosphorylation, which finally dampens fibroblast activation, ECM accumulation, and alleviates the severity of TIF. However, the ubiquitin ligase APC/C is not involved in the MAD2B-mediated SnoN decline, although this process is ubiquitination dependent. In conclusion, our observation proposes that besides cell cycle management, MAD2B has a profibrotic role during fibroblast activation and TIF by suppressing SnoN expression. Targeting the MAD2B-SnoN pathway is a promising intervention for TIF. PMID:27122545

  14. Instandhaltung und Plant Asset Management - zwei Welten?

    NASA Astrophysics Data System (ADS)

    Horch, Alexander

    Der Begriff des Asset Management wird nicht mehr nur in der Finanzwelt gebraucht, sondern seit einigen Jahren auch zunehmend in der produzierenden Industrie, insbesondere in der Prozessindustrie. Die Interessengemeinschaft Automatisierungstechnik der Prozessindustrie, NAMUR, hat bereits im Jahr 2001 eine entsprechende Empfehlung zum Thema anlagennahes Asset Management (Plant Asset Management) vorgelegt. In dieser Empfehlung (NAMUR NE 91) taucht der Begriff 'Instandhaltung' in verschiedener Verwendung 15 Mal auf. Die klassische Instandhaltung ist seit vielen Jahren wohl etabliert und definiert, was die große Anzahl Richtlinien, Beschreibungen und Standards belegt (DIN 31051, VDI 2884, VDI 2888, VDI 2889, VDI 2890). Eine oft geäußerte Kritik dem Plant Asset Management gegenüber ist, dass im Grunde nichts Neues angeboten wird, über die Instandhaltung hinaus. Auf der anderen Seite wird das Plant Asset Management seit über zehn Jahren vermehrt gebraucht und etabliert. Dieser scheinbare Widerspruch soll in diesem Beitrag ausgeräumt werden. Als Motivation sollen drei Beispiele kurz beschrieben werden.

  15. Therapeutisches Management kutaner und genitaler Warzen.

    PubMed

    Ockenfels, Hans Michael

    2016-09-01

    Mindestens 10 % der Bevölkerung erkranken während ihres Lebens an einer Infektion mit humanen Papillomaviren (HPV), welche sich klinisch anhand der Ausbildung kutaner oder genitaler Warzen manifestiert. Obwohl Warzen ubiquitär sind, existieren keine definierten Behandlungen. Warzen zeigen, insbesondere in den ersten sechs Monaten, eine erhöhte Selbstheilungsrate. Dieser Umstand erschwert die Interpretation von Studien, da häufig Patienten mit Neuinfektionen zusammen mit Patienten mit Altinfektionen behandelt werden. Lokalisationen, Größe und Dicke der Warzen sind ebenfalls in den meisten Fällen nicht berücksichtigt. Ziel dieses Übersichtsartikels ist eine Analyse des vorliegenden Studienmaterials, unter der für den klinischen Alltag so wichtigen Berücksichtigung von Subtypen und Lokalisationen. Insbesondere die Abgrenzung zwischen frischen und chronisch-therapieresistenten Verrucae vulgares spiegelt sich in einem Therapiealgorithmus wider. Bei genitalen Warzen wird der Therapiealgorithmus deutlicher durch das Ausmaß der infizierten Fläche als durch das Alter der Warzen bestimmt. Bei immunkompetenten Personen muss es mit den hier aufgezeigten therapeutischen Methoden immer das Ziel sein, eine komplette Abheilung zu erzielen. PMID:27607029

  16. Elektronische Citizen Cards in Deutschland und Europa

    NASA Astrophysics Data System (ADS)

    Kowalski, Bernd

    Meine sehr geehrten Damen und Herren, der Bedarf an elektronischen Identitäten entsteht durch die wachsende Mobilität der Gesellschaft bei einem gleichzeitig steigenden Bedarf an Onlinepräsenz. Diese elektronischen Identitäten machen natürlich auch vor den staatlichen Ausweisen nicht halt, wie zum Beispiel dem Reisepass, aber auch dem Personalausweis und weiteren Ausweisdokumenten. Wobei es bei den staatlich herausgegebenen oder kontrollierten Ausweisen immer um zwei verschiedene Dinge geht: Einmal um die hoheitliche Funktion, wie zum Beispiel beim Reisepass. Hier geht es zum Beispiel darum, in einem Europa mit gefallenen Grenzen und bei freiem Reiseverkehr für alle Personen, die in diesem Raum wohnen, insbesondere auch im Schengener Raum, die Möglichkeit zu schaffen, auch künftig noch Personenkontrollen durchzuführen. Auch der Reiseverkehr über die europäischen Grenzen hinaus ist insofern ein Problem, da die Identitätenprüfung an den Grenzkontrollen immer schwieriger wird. Deswegen braucht man an dieser Stelle Möglichkeiten, um eine Personenüberprüfung durchzuführen, um feststellen zu können, dass diese Person auch zum Dokument gehört.

  17. Fusel Alcohols Regulate Translation Initiation by Inhibiting eIF2B to Reduce Ternary Complex in a Mechanism That May Involve Altering the Integrity and Dynamics of the eIF2B Body

    PubMed Central

    Taylor, Eleanor J.; Campbell, Susan G.; Griffiths, Christian D.; Reid, Peter J.; Slaven, John W.; Harrison, Richard J.; Sims, Paul F.G.; Pavitt, Graham D.; Delneri, Daniela

    2010-01-01

    Recycling of eIF2-GDP to the GTP-bound form constitutes a core essential, regulated step in eukaryotic translation. This reaction is mediated by eIF2B, a heteropentameric factor with important links to human disease. eIF2 in the GTP-bound form binds to methionyl initiator tRNA to form a ternary complex, and the levels of this ternary complex can be a critical determinant of the rate of protein synthesis. Here we show that eIF2B serves as the target for translation inhibition by various fusel alcohols in yeast. Fusel alcohols are endpoint metabolites from amino acid catabolism, which signal nitrogen scarcity. We show that the inhibition of eIF2B leads to reduced ternary complex levels and that different eIF2B subunit mutants alter fusel alcohol sensitivity. A DNA tiling array strategy was developed that overcame difficulties in the identification of these mutants where the phenotypic distinctions were too subtle for classical complementation cloning. Fusel alcohols also lead to eIF2α dephosphorylation in a Sit4p-dependent manner. In yeast, eIF2B occupies a large cytoplasmic body where guanine nucleotide exchange on eIF2 can occur and be regulated. Fusel alcohols impact on both the movement and dynamics of this 2B body. Overall, these results confirm that the guanine nucleotide exchange factor, eIF2B, is targeted by fusel alcohols. Moreover, they highlight a potential connection between the movement or integrity of the 2B body and eIF2B regulation. PMID:20444979

  18. Vortex lattice structures in YNi{sub 2}B{sub 2}C

    SciTech Connect

    Yethiraj, M.; Paul, D.M.; Tomy, C.V.; Forgan, E.M.

    1997-12-01

    The authors observe a flux lattice with square symmetry in the superconductor YNi{sub 2}B{sub 2}C when the applied field is parallel to the c-axis of the crystal. A square lattice observed previously in the isostructural magnetic analog ErNi{sub 2}B{sub 2}C was attributed to the interaction between magnetic order in that system and the flux lattice. Since the Y-based compound does not order magnetically, it is clear that the structure of the flux lattice is unrelated to magnetic order. In fact, they show that the flux lines have a square cross-section when the applied field is parallel to the c-axis of the crystal, since the measured penetration depth along the 100 crystal direction is larger than the penetration depth along the 110 by approximately 60%. This is the likely reason for the square symmetry of the lattice. Although they find considerable disorder in the arrangement of the flux lines at 2.5T, no melting of the vortex lattice was observed.

  19. An infrared spectroscopic study of Li2B4O7

    NASA Astrophysics Data System (ADS)

    Zhigadlo, N. D.; Zhang, M.; Salje, E. K. H.

    2001-07-01

    The temperature evolution of the infrared powder spectra of lithium tetraborate Li2B4O7 has been measured in the infrared region 50-1600 cm-1 and over a temperature range between 20 K and 680 K. In contrast to the sharp B-O bands, the Li-related bands in the region between 300 cm-1 and 510 cm-1 are rather broad even at 20 K. With increasing temperature these bands show a stronger thermal response than in the higher-frequency region: the bands at 350 cm-1 and 424 cm-1 shift significantly in frequency and become very broad above 500 K. The 508 cm-1 band appears to split into two individual bands near 500 K. The broadening of the Li-related bands is probably due to the thermally induced Li disorder. The temperature dependence of the B-O bending and stretching vibrations does not show clear evidence of structural phase transitions in Li2B4O7 occurring in the temperature range between 20 K and 680 K.

  20. Sh3pxd2b Mice Are a Model for Craniofacial Dysmorphology and Otitis Media

    PubMed Central

    Yang, Bin; Tian, Cong; Zhang, Zhi-guang; Han, Feng-chan; Azem, Rami; Yu, Heping; Zheng, Ye; Jin, Ge; Arnold, James E.; Zheng, Qing Y.

    2011-01-01

    Craniofacial defects that occur through gene mutation during development increase vulnerability to eustachian tube dysfunction. These defects can lead to an increased incidence of otitis media. We examined the effects of a mutation in the Sh3pxd2b gene (Sh3pxd2bnee) on the progression of otitis media and hearing impairment at various developmental stages. We found that all mice that had the Sh3pxd2bnee mutation went on to develop craniofacial dysmorphologies and subsequently otitis media, by as early as 11 days of age. We found noteworthy changes in cilia and goblet cells of the middle ear mucosa in Sh3pxd2bnee mutant mice using scanning electronic microscopy. By measuring craniofacial dimensions, we determined for the first time in an animal model that this mouse has altered eustachian tube morphology consistent with a more horizontal position of the eustachian tube. All mutants were found to have hearing impairment. Expression of TNF-α and TLR2, which correlates with inflammation in otitis media, was up-regulated in the ears of mutant mice when examined by immunohistochemistry and semi-quantitative RT-PCR. The mouse model with a mutation in the Sh3pxd2b gene (Sh3pxd2bnee) mirrors craniofacial dysmorphology and otitis media in humans. PMID:21818352

  1. Cotranscriptional histone H2B monoubiquitylation is tightly coupled with RNA polymerase II elongation rate

    PubMed Central

    Fuchs, Gilad; Hollander, Dror; Voichek, Yoav; Ast, Gil

    2014-01-01

    Various histone modifications decorate nucleosomes within transcribed genes. Among these, monoubiquitylation of histone H2B (H2Bub1) and methylation of histone H3 on lysines 36 (H3K36me2/3) and 79 (H3K79me2/3) correlate positively with gene expression. By measuring the progression of the transcriptional machinery along genes within live cells, we now report that H2B monoubiquitylation occurs cotranscriptionally and accurately reflects the advance of RNA polymerase II (Pol II). In contrast, H3K36me3 and H3K79me2 are less dynamic and represent Pol II movement less faithfully. High-resolution ChIP-seq reveals that H2Bub1 levels are selectively reduced at exons and decrease in an exon-dependent stepwise manner toward the 3′ end of genes. Exonic depletion of H2Bub1 in gene bodies is highly correlated with Pol II pausing at exons, suggesting elongation rate changes associated with intron–exon structure. In support of this notion, H2Bub1 levels were found to be significantly correlated with transcription elongation rates measured in various cell lines. Overall, our data shed light on the organization of H2Bub1 within transcribed genes and single out H2Bub1 as a reliable marker for ongoing transcription elongation. PMID:25049226

  2. Cloning and characterization of a third type of human alpha-amylase gene, AMY2B.

    PubMed

    Yokouchi, H; Horii, A; Emi, M; Tomita, N; Doi, S; Ogawa, M; Mori, T; Matsubara, K

    1990-06-15

    We have previously reported concerning the existence of a third type of human alpha-amylase gene, AMY3 [Emi et al., Gene 62 (1988) 229-235; Tomita et al., Gene 76 (1989) 11-18], which is expressed in a lung carcinoid tissue, and differs in nucleotide sequence from the two previously characterized human alpha-amylase genes coding for salivary and pancreatic isozymes, termed AMY1 and AMY2, respectively. Here, we rename this gene AMY2B to coincide with the designation by Gumucio et al. [Mol. Cell Biol. 8 (1988) 1197-1205] and describe its genetic properties as revealed by sequencing studies. It consists of ten major exons whose sequences are highly homologous to those of AMY1 and AMY2. Not only the exons, but also most of the introns seem to be highly conserved, as judged from physical mapping data. The AMY2B gene identified from mRNA in a lung carcinoid tissue has at least two additional untranslated exons in its 5' region; hence the promoter lies far upstream relative to the other two AMY genes. PMID:2401405

  3. Preparation, Purification, and Identification of a Monoclonal Antibody Against NRP2 b1b2 Domain.

    PubMed

    Yang, Yun; Chen, Na; Li, Zhe; Wang, Xian-Jiang; Wang, Sheng-Yu; Tingwu; Luo, Fang-Hong; Yan, Jiang-Hua

    2015-10-01

    First identified as a high-affinity kinase-deficient receptor for class-3 semaphorins and vascular endothelial growth factor (VEGF) families, Neuropilin2 (NRP2) is a transmembrane non-tyrosine-kinase glycoprotein that has a vital function in neuronal patterning. Furthermore, NRP2 expression is often upregulated in cancer tissues and correlated with poor prognosis. In the present study, we report the establishment of a monoclonal antibody specific for NRP2b1b2 domain (NRP2 MAb) through hybridoma method. NRP2 MAb is measured to have a titer of 5.12 × 10(5) against NRP2b1b2 in indirect ELISA. Western blotting, flow cytometry, and immunofluorescence analysis indicate that NRP2 MAb can combine full-length NRP2 in LoVo and SW480 cells. Besides helping further understand NRP2-related pathological mechanisms and cell-signaling pathways, NRP2 MAb may act as a therapeutic agent for cancer in the future. PMID:26492624

  4. High heat transfer oxidizer heat exchanger design and analysis. [RL10-2B engine

    NASA Technical Reports Server (NTRS)

    Kmiec, Thomas D.; Kanic, Paul G.; Peckham, Richard J.

    1987-01-01

    The RL10-2B engine, a derivative of the RL10, is capable of multimode thrust operation. This engine operates at two low thrust levels: tank head idle (THI), which is approximately 1 to 2% of full thrust, and pumped idle (PI), which is 10% of full thrust. Operation at THI provides vehicle propellant settling thrust and efficient engine thermal conditioning; PI operation provides vehicle tank pre-pressurization and maneuver thrust for low-g deployment. Stable combustion of the RL10-2B engine during the low thrust operating modes can be accomplished by using a heat exchanger to supply gaseous oxygen to the propellant injector. The oxidizer heat exchanger (OHE) vaporizes the liquid oxygen using hydrogen as the energy source. The design, concept verification testing and analysis for such a heat exchanger is discussed. The design presented uses a high efficiency compact core to vaporize the oxygen, and in the self-contained unit, attenuates any pressure and flow oscillations which result from unstable boiling in the core. This approach is referred to as the high heat transfer design. An alternative approach which prevents unstable boiling of the oxygen by limiting the heat transfer is referred to as the low heat transfer design and is reported in Pratt & Whitney report FR-19135-2.

  5. Anisotropy of the Vortex Magnetic Field Distribution in LuNi2B2

    NASA Astrophysics Data System (ADS)

    Eskildsen, M. R.; Debeer-Schmitt, L.; Rovira, K.; Jenkins, N.; Dewhurst, C. D.; Bud'Ko, S. L.; Canfield, P. C.

    2008-03-01

    It is well known that the vortex lattice (VL) symmetry and orientation in type-II superconductors is very sensitive to any anisotropy within the screening current plane. A classic example is the sequence of transitions from hexagonal to rhombic to square symmetry, which was first observed in the borocarbide superconductors and explained by a Fermi surface anisotropy coupled with the non-local electrodynamics responsible for vortex-vortex interactions. Recently, however, this is mounting experimental evidence for a strong gap anisotropy and possible point nodes in the basal plane of these materials. Here we report on small-angle neutron scattering studies of the VL in a carefully annealed, high quality LuNi2B2C single crystal, which permitted us to measure the VL form factor for a large number of reflections. These measurements allow a reconstruction of the real space profile of the magnetic field around the vortices, reflecting the basal plane anisotropy of the screening currents in LuNi2B2C. The results will be compared to predictions for both Fermi surface and gap anisotropies, and will serve as a valuable reference for more complicated compounds as e.g. Sr2RuO4, heavy fermions and high-Tc's.

  6. Summary report on the fuel performance modeling of the AFC-2A, 2B irradiation experiments

    SciTech Connect

    Pavel G. Medvedev

    2013-09-01

    The primary objective of this work at the Idaho National Laboratory (INL) is to determine the fuel and cladding temperature history during irradiation of the AFC-2A, 2B transmutation metallic fuel alloy irradiation experiments containing transuranic and rare earth elements. Addition of the rare earth elements intends to simulate potential fission product carry-over from pyro-metallurgical reprocessing. Post irradiation examination of the AFC-2A, 2B rodlets revealed breaches in the rodlets and fuel melting which was attributed to the release of the fission gas into the helium gap between the rodlet cladding and the capsule which houses six individually encapsulated rodlets. This release is not anticipated during nominal operation of the AFC irradiation vehicle that features a double encapsulated design in which sodium bonded metallic fuel is separated from the ATR coolant by the cladding and the capsule walls. The modeling effort is focused on assessing effects of this unanticipated event on the fuel and cladding temperature with an objective to compare calculated results with the temperature limits of the fuel and the cladding.

  7. Association of eukaryotic translation initiation factor eIF2B with fully solubilized CXCR4.

    PubMed

    Palmesino, Elena; Apuzzo, Tiziana; Thelen, Sylvia; Mueller, Bernd; Langen, Hanno; Thelen, Marcus

    2016-06-01

    Chemokine receptors are key regulators of leukocyte trafficking but also have an important role in development, tumor growth, and metastasis. Among the chemokine receptors, CXCR4 is the only one that leads to perinatal death when genetically ablated in mice, indicating a more-widespread function in development. To identify pathways that are activated downstream of CXCR4, a solubilization protocol was elaborated, which allows for the isolation of the endogenous receptor from human cells in its near-native conformation. Solubilized CXCR4 is recognized by the conformation-sensitive monoclonal antibody 12G5 and retains the ability to bind CXCL12 in solution, which was abolished in the presence of receptor antagonists. Mass spectrometry of CXCR4 immunoprecipitates revealed a specific interaction with the pentameric eukaryotic translation initiation factor 2B. The observation that the addition of CXCL12 leads to the dissociation of eukaryotic translation initiation factor 2B from CXCR4 suggests that stimulation of the receptor may trigger the local protein synthesis required for efficient cell movement. PMID:26609049

  8. Transport properties along c-axis of DyNi2B2C

    NASA Astrophysics Data System (ADS)

    Lee, W. C.

    2014-12-01

    We have measured the resistivity along c-axis ρc(H, T) of DyNi2B2C with the applied magnetic field H perpendicular to c-axis for 0 kG < H < 4 kG and temperature range 2 K < T < 300 K. From these, the superconducting upper critical field HC2(T) curve of DyNi2B2C for the c-axis was constructed and our HC2(T) curve from ρc(H, T) measurement has been compared with that from previous known ρab(H, T) result. With additional magnetization isotherms M(H, T) for H ⊥ c and H ∥ c-axis, the anisotropy in HC2(T) curves of the magnetic structure DyNi2N2C, which has the superconducting transition temperature TC is lower than the Néel temperatures TN, might be originated from the additional anisotropic magnetic Dy3+ sublattice.

  9. C-axis Transport Properties of DyNi2 B2 C

    NASA Astrophysics Data System (ADS)

    Lee, W. C.

    2014-03-01

    The resistivity along c-axis ρc(H,T) of DyNi2B2C have been measured with the applied magnetic field H perpendicular and parallel to c-axis, 0 kG 2B2C for the c-axis were constructed for each magnetic fields and our HC2(T) curves from ρc(H,T) measurement have been compared with those from previous known ρab(H,T) results. Since RNi2N2C (R = non magnetic rare earth element) has isotropic electronic structure and properties, the anisotropy in HC2(T) curves of the magnetic DyNi2N2C, which has the superconducting transition temperature, TC, is lower than the Néel temperatures, TN, is thought to be originated from the anisotropic magnetic Dy +3 sublattice.

  10. Analysis of Kepler's Short-cadence Photometry for TrES-2b

    NASA Astrophysics Data System (ADS)

    Kipping, David; Bakos, Gáspár

    2011-05-01

    We present an analysis of 18 short-cadence (SC) transit light curves of TrES-2b using quarter 0 (Q0) and quarter 1 (Q1) from the Kepler Mission. The photometry is of unprecedented precision, 237 ppm minute-1, allowing for the most accurate determination of the transit parameters yet obtained for this system. Global fits of the transit photometry, radial velocities, and known transit times are used to obtain a self-consistent set of refined parameters for this system, including updated stellar and planetary parameters. Special attention is paid to fitting for limb darkening and eccentricity. We place an upper limit on the occultation depth to be <72.9 ppm to 3σ confidence, indicating TrES-2b has the lowest determined geometric albedo for an exoplanet, of Ag < 0.146. We also produce a transit timing analysis using Kepler's SC data and demonstrate exceptional timing precision at the level of a few seconds for each transit event. With 18 fully sampled transits at such high precision, we are able to produce stringent constraints on the presence of perturbing planets, Trojans, and extrasolar moons. We introduce the novel use of control data to identify phasing effects. We also exclude the previously proposed hypotheses of short-period transit time variation and additional transits but find that the hypothesis of long-term inclination change is neither supported nor refuted by our analysis. Based on archival data of the Kepler telescope.

  11. Macroscale production of crystalline interferon alfa-2b in microgravity on STS-52

    NASA Astrophysics Data System (ADS)

    Nagabhushan, Tattanahalli L.; Reichert, Paul; Long, Marianna M.; DeLucas, Lawrence J.; Bugg, Charles E.

    1995-01-01

    Macroscale crystallization of zinc interferon alfa-2b was achieved on STS-52 in October 1992 in the Protein Crystallization Facility. Conditions for crystallization were established by adapting a microscale vapor diffusion method to a macroscale temperature induction method. A series of earth based pilot experiments established conditions to reproducibly crystallize zinc interferon alfa-2b in high yield and under cleanroom conditions. As a control for the STS-52 mission, a ground experiment was run simultaneously and in the same configuration as the flight experiment. Greater than 95% of the available protein crystallized in both the ground and flight experiments. Using a battery of physical, biochemical and biological characterization assays, demonstrated that sample processing, polysulfone bottle confinement and the conditions used for crystallization did not have a negative effect on protein integrity. Redissolved crystals from the flight and ground experiments showed full biological activity in a cytopathic effect inhibition assay as compared to an interferon control standard. Morphometric analysis comparing the overall length and width of the derived crystals showed a 2.4 fold increase in the length and width of the space grown crystals as compared to earth grown crystals. Space grown crystals have remained a stable free flowing suspension for over 2 years. Based on these results, further experiments are envisioned to investigate macroscale crystallization of biologically active macromolecules in microgravity.

  12. ANALYSIS OF KEPLER'S SHORT-CADENCE PHOTOMETRY FOR TrES-2b

    SciTech Connect

    Kipping, David; Bakos, Gaspar

    2011-05-20

    We present an analysis of 18 short-cadence (SC) transit light curves of TrES-2b using quarter 0 (Q0) and quarter 1 (Q1) from the Kepler Mission. The photometry is of unprecedented precision, 237 ppm minute{sup -1}, allowing for the most accurate determination of the transit parameters yet obtained for this system. Global fits of the transit photometry, radial velocities, and known transit times are used to obtain a self-consistent set of refined parameters for this system, including updated stellar and planetary parameters. Special attention is paid to fitting for limb darkening and eccentricity. We place an upper limit on the occultation depth to be <72.9 ppm to 3{sigma} confidence, indicating TrES-2b has the lowest determined geometric albedo for an exoplanet, of A{sub g} < 0.146. We also produce a transit timing analysis using Kepler's SC data and demonstrate exceptional timing precision at the level of a few seconds for each transit event. With 18 fully sampled transits at such high precision, we are able to produce stringent constraints on the presence of perturbing planets, Trojans, and extrasolar moons. We introduce the novel use of control data to identify phasing effects. We also exclude the previously proposed hypotheses of short-period transit time variation and additional transits but find that the hypothesis of long-term inclination change is neither supported nor refuted by our analysis.

  13. Histone chaperone Chz1p regulates H2B ubiquitination and subtelomeric anti-silencing

    PubMed Central

    Wan, Yakun; Chiang, Jung-Hsien; Lin, Chan-Hsien; Arens, Christina E.; Saleem, Ramsey A.; Smith, Jennifer J.; Aitchison, John D.

    2010-01-01

    Chz1p is a histone chaperone that interacts physically and functionally with the histone variant Htz1p, which has been implicated in establishing and maintaining boundaries between transcriptionally inactive heterochromatin and active euchromatin. To investigate the role of Chz1p in chromatin organization, we performed genome-wide expression arrays and chromatin immunoprecipitations of SIR complex components and modified histones in a CHZ1 deletion strain. Deletion of CHZ1 led to reduced ubiquitination of subtelomere-associated H2B, reduced subtelomeric H3K79 di-methylation, and increased binding of Sir3p, and Sir4p at telomere-distal euchromatin regions, correlating with decreased gene expression in subtelomeric regions. This anti-silencing defect appears to be mediated by enhanced association of de-ubiquitinase Ubp10p with subtelomeric DNA, as detected by chromatin immunoprecipitation analysis. In support of this, we show that deletion of UBP10 can antagonize the subtelomeric silencing phenotype of Δchz1. Taken together, the results demonstrate a novel role for Chz1p in epigenetic regulation, through H2B de-ubiquitination by Ubp10p. PMID:20008511

  14. Impact assessment of draft DOE Order 5820.2B. Radioactive Waste Technical Support Program

    SciTech Connect

    1995-04-01

    The Department of Energy (DOE) has prepared a revision to DOE Order 5820.2A, entitled ``Radioactive Waste Management.`` DOE issued DOE Order 5820.2A in September 1988 and, as the title implies, it covered only radioactive waste forms. The proposed draft order, entitled ``Waste Management,`` addresses the management of both radioactive and nonradioactive waste forms. It also includes spent nuclear fuel, which DOE does not consider a waste. Waste forms covered include hazardous waste, high-level waste, transuranic (TRU) waste, low-level radioactive waste, uranium and thorium mill tailings, mixed waste, and sanitary waste. The Radioactive Waste Technical Support Program (TSP) of Leached Idaho Technologies Company (LITCO) is facilitating the revision of this order. The EM Regulatory Compliance Division (EM-331) has requested that TSP estimate the impacts and costs of compliance with the revised order. TSP requested Dames & Moore to aid in this assessment by comparing requirements in Draft Order 5820.2B to ones in DOE Order 5820.2A and other DOE orders and Federal regulations. The assessment started with a draft version of 5820.2B dated January 14, 1994. DOE has released three updated versions of the draft order since then (dated May 20, 1994; August 26, 1994; and January 23, 1995). Each time DOE revised the order, Dames and Moore updated the assessment work to reflect the text changes. This report reflects the January 23, 1995 version of the draft order.

  15. Thermochemical properties of polycyclic aromatic hydrocarbons (PAH) from G3MP2B3 calculations.

    PubMed

    Blanquart, Guillaume; Pitsch, Heinz

    2007-07-19

    In this article, we present a new database of thermodynamic properties for polycyclic aromatic hydrocarbons (PAH). These large aromatic species are formed in very rich premixed flames and in diffusion flames as part of the gas-phase chemistry. PAH are commonly assumed to be the intermediates leading to soot formation. Therefore, accurate prediction of their thermodynamic properties is required for modeling soot formation. The present database consists of 46 species ranging from benzene (C6H6) to coronene (C24H12) and includes all the species usually present in chemical mechanisms for soot formation. Geometric molecular structures are optimized at the B3LYP/6-31++G(d,p) level of theory. Heat capacity, entropy, and energy content are calculated from these optimized structures. Corrections for hindered rotor are applied on the basis of torsional potentials obtained from second-order Møller-Plesset perturbation (MP2) and Dunning's consistent basis sets (cc-pVDZ). Enthalpies of formation are calculated using the mixed G3MP2//B3 method. Finally, a group correction is applied to account for systematic errors in the G3MP2//B3 computations. The thermodynamic properties for all species are available in NASA polynomial form at the following address: http://www.stanford.edu/group/pitsch/. PMID:17595062

  16. Preclinical evaluation of recombinant human IFNα2b-containing magnetoliposomes for treating hepatocellular carcinoma

    PubMed Central

    Ye, Hui; Tong, Jiansong; Wu, Jianzhang; Xu, Xia; Wu, Shenjie; Tan, Botao; Shi, Mengjing; Wang,