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Sample records for ccr mag v1

  1. CCR1

    African Journals Online (AJOL)

    inflammatory protein II; Bioinformatics; Protease digestion; HEK293 cells; Radioligand binding. Tropical ... development of many diseases. ... diseases, antagonism of CCR1 has become an ..... importance of molecular conformation in terms of.

  2. Clinical Case Registries (CCR)

    Data.gov (United States)

    Department of Veterans Affairs — The Clinical Case Registries (CCR) replaced the former Immunology Case Registry and the Hepatitis C Case Registry with local and national databases. The CCR:HIV and...

  3. THOR Fluxgate Magnetometer (MAG)

    Science.gov (United States)

    Nakamura, Rumi; Eastwood, Jonathan; Magnes, Werner; Carr, Christopher, M.; O'Brien, Helen, L.; Narita, Yasuhito; K, Chen, Christopher H.; Berghofer, Gerhard; Valavanoglou, Aris; Delva, Magda; Plaschke, Ferdinand; Cupido, Emanuele; Soucek, Jan

    2017-04-01

    Turbulence Heating ObserveR (THOR) is the first mission ever flown in space dedicated to plasma turbulence. The fluxgate Magnetometer (MAG) measures the background to low frequency magnetic field. The high sensitivity measurements of MAG enable to characterize the nature of turbulent fluctuations as well as the large-scale context. MAG will provide the reference system for determining anisotropy of field fluctuations, pitch-angle and gyro-phase of particles. The design of the magnetometer consists of two tri-axial sensors and the related magnetometer electronics; the electronics are hosted on printed circuit boards in the common electronics box of the fields and wave processor (FWP). A fully redundant two- sensor system mounted on a common boom and the new miniaturized low noise design based on MMS and Solar Orbiter instruments enable accurate measurement throughout the region of interest for THOR science. The usage of the common electronics hosted by FWP guarantees to fulfill the required timing accuracy with other fields measurements. These improvements are important to obtain precise measurements of magnetic field, which is essential to estimate basic plasma parameters and correctly identify the spatial and temporal scales of the turbulence. Furthermore, THOR MAG provides high quality data with sufficient overlap with the Search Coil Magnetometer (SCM) in frequency space to obtain full coverage of the wave forms over all the frequencies necessary to obtain the full solar wind turbulence spectrum from MHD to kinetic range with sufficient accuracy. We discuss the role of MAG in THOR key science questions and present the new developments during Phase A such as the finalised instrument design, MAG relevant requirement, and new calibraion schemes.

  4. Rouw mag er zijn

    Directory of Open Access Journals (Sweden)

    Marlieke Moors

    2015-12-01

    Full Text Available ABSTRACTGrieving is allowedGrief is a human experience. Every form of loss shapes you into the human being you are today. Contrary to what earlier, unproven grief models postulate, grief does not have an end point. That is, bereavement does not have to be completely processed, but it should be integrated into someone’s life. The outdated grief models were often interpreted and used in a normative way, which led to a normative standard model. This portraits the belief that every mourner would experience similar symptoms and would go through a fixed pattern of phases. However, the updated vision emphasizes the individual and unique process of coping with loss: norms concerning grief should be banned. By means of literature research, interviews with professionals and personal experiences, it became clear that finding an equilibrium between restoration-orientated and loss-orientated coping styles is most beneficial. An important aspect in finding this balance is meaningfulness. Furthermore, the ability to bear a loss and to adapt accordingly are important components. Lastly, attaching significance to a loss is a constructive way of integrating the loss into one’s life. The death of a loved one should therefore not be forgotten or tucked away. After all, grief is the price we pay for love. SAMENVATTINGRouw mag er zijnRouw is een menselijke ervaring en elk verlies vormt je als mens. Rouw heeft, in tegenstelling tot wat de verouderde, niet bewezen rouwmodellen beweren, geen eindpunt. Verlies hoeft namelijk niet verwerkt te worden, maar moet juist geïntegreerd worden in iemands leven. De verouderde rouwmodellen zijn vaak normatief opgevat en toegepast, waaruit een normatief standaardmodel is ontstaan. Daarbij werd gedacht dat elke rouwende dezelfde symptomen zou vertonen en het rouwproces volgens vaste fasen zou verlopen. Binnen de vernieuwde visie wordt er juist van uitgegaan dat elk individu een unieke manier van reageren op rouw heeft. Er zou

  5. BioMagResBank.

    NARCIS (Netherlands)

    Ulrich, E.L.; Akutsu, H.; Doreleijers, J.; Harano, Y.; Ioannidis, Y.E.; Lin, J.; Livny, M.; Mading, S.; Maziuk, D.; Miller, Z.; Nakatani, E.; Schulte, C.F.; Tolmie, D.E.; Wenger, R.K.; Yao, H.; Markley, J.L.

    2008-01-01

    The BioMagResBank (BMRB: www.bmrb.wisc.edu) is a repository for experimental and derived data gathered from nuclear magnetic resonance (NMR) spectroscopic studies of biological molecules. BMRB is a partner in the Worldwide Protein Data Bank (wwPDB). The BMRB archive consists of four main data

  6. Transrapid MagLev system

    Energy Technology Data Exchange (ETDEWEB)

    Heinrich, K [MVP Versuchs- und Planungsgesellschaft fuer Magnetbahnsysteme mbH, Muenchen (Germany); Kretzschmar, R [Transrapid International Gesellschaft fuer Magnetbahnsysteme, Muenchen (Germany); eds.

    1989-01-01

    The Transrapid MagLev System is a new world leader in advanced technology which opens up novel possibilities in tracked high-speed transport. At speeds of 400 kmph and beyond the Transrapid hovers above its guideway. It is driven by a linear motor. Electromagnets provide guidance and support. In 22 chapters a large number of highly qualified engineers offer a detailed and comprehensive description in this book of a radically new transport system, which uses a startling alternative of the wheel, the prime mover of mankind for many thousands of years. They introduce their subjects with a survey of the development and of the practical possibilities of this novel high-speed transport system, and go on to describe in detail the various types of guideway. The contributions about the high-speed switch and the demands of the geometry of the guideway are followed by a chapter on the guideway equipment. The contactless propulsion technology, the drive, and its power supply are dealt with in detail. The designers of the Transrapid MagLev railway also describe all the functions and installations serving the safety, supervision, and control of the running operation. A large space is devoted also to the description of the support- and guidance system and of the vehicle. Needless to say the complete description of this new transport system deals in great detail with the practical possibilities and with the trial operation on the Emsland Transrapid Test Facility. This unique publication concludes with a contribution on maglev developments abroad and with a chronology of the Transrapid MagLev System. (GL).

  7. Peripheral Blood CCR4+CCR6+ and CXCR3+CCR6+ CD4+ T Cells Are Highly Permissive to HIV-1 Infection

    OpenAIRE

    Gosselin, Annie; Monteiro, Patricia; Chomont, Nicolas; Diaz-Griffero, Felipe; Said, Elias A.; Fonseca, Simone; Wacleche, Vanessa; El-Far, Mohamed; Boulassel, Mohamed-Rachid; Routy, Jean-Pierre; Sekaly, Rafick-Pierre; Ancuta, Petronela

    2009-01-01

    There is limited knowledge on the identity of primary CD4+ T cell subsets selectively targeted by HIV-1 in vivo. In this study, we established a link between HIV permissiveness, phenotype/homing potential, and lineage commitment in primary CD4+ T cells. CCR4+CCR6+, CCR4+CCR6−, CXCR3+CCR6+, and CXCR3+CCR6− T cells expressed cytokines and transcription factors specific for Th17, Th2, Th1Th17, and Th1 lineages, respectively. CCR4+CCR6+ and CXCR3+CCR6+ T cells expressed the HIV coreceptors CCR5 a...

  8. Regulation of CCR7-dependent cell migration through?CCR7 homodimer formation

    OpenAIRE

    Kobayashi, Daichi; Endo, Masataka; Ochi, Hirotaka; Hojo, Hironobu; Miyasaka, Masayuki; Hayasaka, Haruko

    2017-01-01

    The chemokine receptor CCR7 contributes to various physiological and pathological processes including T cell maturation, T cell migration from the blood into secondary lymphoid tissues, and tumor cell metastasis to lymph nodes. Although a previous study suggested that the efficacy of CCR7 ligand-dependent T cell migration correlates with CCR7 homo- and heterodimer formation, the exact extent of contribution of the CCR7 dimerization remains unclear. Here, by inducing or disrupting CCR7 dimers,...

  9. SuperMAG: Present and Future Capabilities

    Science.gov (United States)

    Hsieh, S. W.; Gjerloev, J. W.; Barnes, R. J.

    2009-12-01

    SuperMAG is a global collaboration that provides ground magnetic field perturbations from a long list of stations in the same coordinate system, identical time resolution and with a common baseline removal approach. This unique high quality dataset provides a continuous and nearly global monitoring of the ground magnetic field perturbation. Currently, only archived data are available on the website and hence it targets basic research without any operational capabilities. The existing SuperMAG software can be easily adapted to ingest real-time or near real-time data and provide a now-casting capability. The SuperDARN program has a long history of providing near real-time maps of the northern hemisphere electrostatic potential and as both SuperMAG and SuperDARN share common software it is relatively easy to adapt these maps for global magnetic perturbations. Magnetometer measurements would be assimilated by the SuperMAG server using a variety of techniques, either by downloading data at regular intervals from remote servers or by real-time streaming connections. The existing SuperMAG analysis software would then process these measurements to provide the final calibrated data set using the SuperMAG coordinate system. The existing plotting software would then be used to produce regularly updated global plots. The talk will focus on current SuperMAG capabilities illustrating the potential for now-casting and eventually forecasting.

  10. A National MagLev Transportation System

    Science.gov (United States)

    Wright, Michael R.

    2003-01-01

    The case for a national high-speed magnetic-levitation (MagLev) transportation system is presented. Focus is on current issues facing the country, such as national security, the economy, transportation, technology, and the environment. NASA s research into MagLev technology for launch assist is also highlighted. Further, current socio-cultural norms regarding motor-vehicle-based transportation systems are questioned in light of the problems currently facing the U.S. The multidisciplinary benefits of a long-distance MagLev system support the idea that such a system would be an important element of a truly multimodal U.S. transportation infrastructure.

  11. Molekulare Klonierung, stabile Transfektion und funktionelle Expression der murinen Chemokinrezeptoren Ccr2 und Ccr5

    OpenAIRE

    Simonis, Christopher

    2009-01-01

    The two chemokine receptors CCR2 and CCR5 play important roles in the recruitment and activation of monocytes/macrophages and T-lymphocytes at sites of infection and inflammation. To further examine their function, I cloned the two murine chemokine receptors Ccr2 and Ccr5 from genomic mouse DNA by a PCR-based cloning strategy and functionally expressed them in stably transfected CHO-cells. These cells were used to generate the first monoclonal antibodies against Ccr2 and Ccr5.

  12. Nuclear power plant V-1

    International Nuclear Information System (INIS)

    1998-01-01

    The nuclear power plant Bohunice V -1 is briefly described. This NPP consists from two reactor units. Their main time characteristics are (Reactor Unit 1, Reactor Unit 2): beginning of construction - 24 April 1972; first controlled reactor power - 27 November 1978, 15 March 1980; connection to the grid - 17 December 1978, 26 March 1980; commercial operation - 1 April 1980, 7 January 1981. This leaflet contains: NPP V-1 construction; Major technological equipment (Primary circuit: Nuclear reactor [WWER 440 V230 type reactor];Steam generator; Reactor Coolant Pumps; Primary Circuit Auxiliary Systems. Secondary circuit: Turbine generators, Nuclear power plant electrical equipment; power plant control) and technical data

  13. Complex formation of technetium with the methyl esters of MAG2 and MAG1

    International Nuclear Information System (INIS)

    Noll, B.; Noll, S.; Grosse, B.; Johannsen, B.; Spies, H.

    1993-01-01

    Mercaptoacetylglycine methyl ester (MAG 2 ester) and mercaptoacetyldiglycine methyl ester (MAG 1 ester) were included to investigate complex formation of SH/amide ligands with technetium. The studies are aimed at finding out how blocking the carboxylic groups influences the complexation reaction, with a view to finding an approach to new lipophilic species. (orig./BBR)

  14. Nuclear power plant V-1

    International Nuclear Information System (INIS)

    1999-01-01

    In this leaflet the short history of commissioning of Bohunice V-1 NPP is reviewed (beginning of construction 24 April 1972; First controlled reactor power, Reactor Unit 1 (RU1): 27 November 1978, Reactor Unit 2 (RU2): 15 March 1980; Connection to the grid: RU1 17 December 1978, RU2 26 March 1980; Commercial operation: RU1 1 April 1980, RU2 7 January 1981. The scheme of the nuclear reactor WWER 440/V230 is depicted. The major technological equipment (primary circuit, nuclear reactor, steam generators, reactor coolant pumps, primary circuit auxiliary systems, secondary circuit, turbine generators, NPP electrical equipment, and power plant control) are described. Technical data of the Bohunice V-1 NPP are presented

  15. Tehnologija izrade rasvjetnog stupa MAG postupkom zavarivanja

    OpenAIRE

    Plantić, Miroslav

    2016-01-01

    Završni rad sastoji se od teoretskog i praktičnog dijela. Opisana je tehnologija izrade višekutnog rasvjetnog stupa visine 8 metara koji se koristi za uličnu rasvjetu.U teoretskom djelu kratko je obuhvaćena povijest zavarivanja te su istaknute najvažnije godine i osoba koje su proučavale tehnologiju zavarivanja. Objašnjeni su pojmovi vezani uz zavarivanje, razrađena je podjela postupaka zavarivanja, a detaljno je opisan MAG postupak. Opisana je oprema kod MAG zavarivanja te princip rada. Nave...

  16. Study on the stability of MAG 3

    CERN Document Server

    Aungurarat, A; Thuntawewadthananon, T

    2000-01-01

    Tc 9 sup 9 sup m -MAG 3 ([(N-(N-(N-(mercaptoacetyl) glycyl)glycyl) glycinato (2-) N, N', N sup , S) oxo technetate (2-)]) was prepared for a good renal imaging agent. The two chromatographic methods for analysis of radiochemical purity investigated that the kit could be used with sodium pertechnetate (Technetium-9 sup 9 sup m) up to 25 mCi, volume 2-5 ml and the Tc9 sup 9 sup m -MAG 3 complex reached maximum at 15 mins. The shelf life of the complex and the expiry date of the kit were 4 hrs and 6 months respectivily.

  17. Study on the stability of MAG 3

    International Nuclear Information System (INIS)

    Aungurarat, Angkanan; Ngamprayad, Tippanan; Thuntawewadthananon, Twesak

    2000-01-01

    Tc 9 9m -MAG 3 ([(N-(N-(N-(mercaptoacetyl) glycyl)glycyl) glycinato (2-) N, N', N , S) oxo technetate (2-)]) was prepared for a good renal imaging agent. The two chromatographic methods for analysis of radiochemical purity investigated that the kit could be used with sodium pertechnetate (Technetium-9 9m ) up to 25 mCi, volume 2-5 ml and the Tc9 9m -MAG 3 complex reached maximum at 15 mins. The shelf life of the complex and the expiry date of the kit were 4 hrs and 6 months respectivily

  18. CCR+: Metadata Based Extended Personal Health Record Data Model Interoperable with the ASTM CCR Standard.

    Science.gov (United States)

    Park, Yu Rang; Yoon, Young Jo; Jang, Tae Hun; Seo, Hwa Jeong; Kim, Ju Han

    2014-01-01

    Extension of the standard model while retaining compliance with it is a challenging issue because there is currently no method for semantically or syntactically verifying an extended data model. A metadata-based extended model, named CCR+, was designed and implemented to achieve interoperability between standard and extended models. Furthermore, a multilayered validation method was devised to validate the standard and extended models. The American Society for Testing and Materials (ASTM) Community Care Record (CCR) standard was selected to evaluate the CCR+ model; two CCR and one CCR+ XML files were evaluated. In total, 188 metadata were extracted from the ASTM CCR standard; these metadata are semantically interconnected and registered in the metadata registry. An extended-data-model-specific validation file was generated from these metadata. This file can be used in a smartphone application (Health Avatar CCR+) as a part of a multilayered validation. The new CCR+ model was successfully evaluated via a patient-centric exchange scenario involving multiple hospitals, with the results supporting both syntactic and semantic interoperability between the standard CCR and extended, CCR+, model. A feasible method for delivering an extended model that complies with the standard model is presented herein. There is a great need to extend static standard models such as the ASTM CCR in various domains: the methods presented here represent an important reference for achieving interoperability between standard and extended models.

  19. The frequency of CCR5 promoter polymorphisms and CCR5 32 mutation in Iranian populations

    Directory of Open Access Journals (Sweden)

    Mohammad Zare-Bidaki

    2015-04-01

    Full Text Available Evidence showed that chemokines serve as pro-migratory factors for immune cells. CCL3, CCL4 and CCL5, as the main CC  chemokines subfamily members, activate immune cells through binding to CC chemokine receptor 5 or CCR5. Macrophages, NK cells and T lymphocytes express CCR5 and thus, affected CCR5 expression or functions could be associated with altered immune responses. Deletion of 32 base pairs (D 32 in the exon 1 of the CCR5 gene, which is known as CCR5 D 32 mutation causes down regulation and malfunction of the molecule. Furthermore, it has been evidenced that three polymorphisms in the promoter region of CCR5 modulate its expression. Altered CCR5 expression in microbial infection and immune related diseases have been reported by several researchers but the role of CCR5 promoter polymorphisms and CCR5 D 32 mutation in Iranian patients suffering from these diseases are controversial. Due to the fact that Iranian people have different genetic backgrounds compared to other ethnics, hence, CCR5 promoter polymorphisms and CCR5 D 32 mutation association with the diseases may be different in Iranian patients. Therefore, this review addresses the most recent information regarding the prevalence as well as association of the mutation and polymorphisms in Iranian patients with microbial infection and immune related diseases as along with normal population.

  20. CCR2-64I polymorphism is not associated with altered CCR5 expression or coreceptor function.

    Science.gov (United States)

    Mariani, R; Wong, S; Mulder, L C; Wilkinson, D A; Reinhart, A L; LaRosa, G; Nibbs, R; O'Brien, T R; Michael, N L; Connor, R I; Macdonald, M; Busch, M; Koup, R A; Landau, N R

    1999-03-01

    A polymorphism in the gene encoding CCR2 is associated with a delay in progression to AIDS in human immunodeficiency virus (HIV)-infected individuals. The polymorphism, CCR2-64I, changes valine 64 of CCR2 to isoleucine. However, it is not clear whether the effect on AIDS progression results from the amino acid change or whether the polymorphism marks a genetically linked, yet unidentified mutation that mediates the effect. Because the gene encoding CCR5, the major coreceptor for HIV type 1 primary isolates, lies 15 kb 3' to CCR2, linked mutations in the CCR5 promoter or other regulatory sequences could explain the association of CCR2-64I with slowed AIDS pathogenesis. Here, we show that CCR2-64I is efficiently expressed on the cell surface but does not have dominant negative activity on CCR5 coreceptor function. A panel of peripheral blood mononuclear cells (PBMC) from uninfected donors representing the various CCR5/CCR2 genotypes was assembled. Activated primary CD4(+) T cells of CCR2 64I/64I donors expressed cell surface CCR5 at levels comparable to those of CCR2 +/+ donors. A slight reduction in CCR5 expression was noted, although this was not statistically significant. CCR5 and CCR2 mRNA levels were nearly identical for each of the donor PBMC, regardless of genotype. Cell surface CCR5 and CCR2 levels were more variable than mRNA transcript levels, suggesting that an alternative mechanism may influence CCR5 cell surface levels. CCR2-64I is linked to the CCR5 promoter polymorphisms 208G, 303A, 627C, and 676A; however, in transfected promoter reporter constructs, these did not affect transcriptional activity. Taken together, these findings suggest that CCR2-64I does not act by influencing CCR5 transcription or mRNA levels.

  1. CCR2, CCR5, and CXCL12 variation and HIV/AIDS in Papua New Guinea.

    Science.gov (United States)

    Mehlotra, Rajeev K; Hall, Noemi B; Bruse, Shannon E; John, Bangan; Zikursh, Melinda J Blood; Stein, Catherine M; Siba, Peter M; Zimmerman, Peter A

    2015-12-01

    Polymorphisms in chemokine receptors, serving as HIV co-receptors, and their ligands are among the well-known host genetic factors associated with susceptibility to HIV infection and/or disease progression. Papua New Guinea (PNG) has one of the highest adult HIV prevalences in the Asia-Pacific region. However, information regarding the distribution of polymorphisms in chemokine receptor (CCR5, CCR2) and chemokine (CXCL12) genes in PNG is very limited. In this study, we genotyped a total of nine CCR2-CCR5 polymorphisms, including CCR2 190G >A, CCR5 -2459G >A and Δ32, and CXCL12 801G >A in PNG (n=258), North America (n=184), and five countries in West Africa (n=178). Using this data, we determined previously characterized CCR5 haplotypes. In addition, based on the previously reported associations of CCR2 190, CCR5 -2459, CCR5 open reading frame, and CXCL12 801 genotypes with HIV acquisition and/or disease progression, we calculated composite full risk scores, considering both protective as well as susceptibility effects of the CXCL12 801 AA genotype. We observed a very high frequency of the CCR5 -2459A allele (0.98) in the PNG population, which together with the absence of Δ32 resulted in a very high frequency of the HHE haplotype (0.92). These frequencies were significantly higher than in any other population (all P-valuesnew insights regarding CCR5 variation in the PNG population, and suggest that the collective variation in CCR2, CCR5, and CXCL12 may increase the risk of HIV/AIDS in a large majority of Papua New Guineans. Copyright © 2015 Elsevier B.V. All rights reserved.

  2. Implementation of cargo MagLev in the United States

    Energy Technology Data Exchange (ETDEWEB)

    Rose, Chris R [Los Alamos National Laboratory; Peterson, Dean E [Los Alamos National Laboratory; Leung, Eddie M [MAGTEC ENGINEERING

    2008-01-01

    Numerous studies have been completed in the United States, but no commercial MagLev systems have been deployed. Outside the U.S., MagLev continues to attract funding for research, development and implementation. A brief review of recent global developments in MagLev technology is given followed by the status of MagLev in the U.S. The paper compares the cost of existing MagLev systems with other modes of transport, notes that the near-term focus of MagLev development in the U.S. should be for cargo, and suggests that future MagLev systems should be for very high speed cargo. The Los Angeles to Port of Los Angeles corridor is suggested as a first site for implementation. The benefits of MagLev are described along with suggestions on how to obtain funding.

  3. Human Eosinophils Express Functional CCR7

    Science.gov (United States)

    Ueki, Shigeharu; Estanislau, Jessica; Weller, Peter F.

    2013-01-01

    Human eosinophils display directed chemotactic activity toward an array of soluble chemokines. Eosinophils have been observed to migrate to draining lymph nodes in experimental models of allergic inflammation, yet it is unknown whether eosinophils express CCR7, a key chemokine receptor in coordinating leukocyte trafficking to lymph nodes. The purpose of this study is to demonstrate expression of CCR7 by human eosinophils and functional responses to CCL19 and CCL21, the known ligands of CCR7. Human eosinophils were purified by negative selection from healthy donors. CCR7 expression of freshly purified, unstimulated eosinophils and of IL-5–primed eosinophils was determined by flow cytometry and Western blot. Chemotaxis to CCL19 and CCL21 was measured in transwell assays. Shape changes to CCL19 and CCL21 were analyzed by flow cytometry and microscopy. Calcium fluxes of fluo-4 AM–loaded eosinophils were recorded by flow cytometry after chemokine stimulation. ERK phosphorylation of CCL19- and CCL21-stimulated eosinophils was measured by Western blot and Luminex assay. Human eosinophils expressed CCR7 as demonstrated by flow cytometry and Western blots. Eosinophils exhibited detectable cell surface expression of CCR7. IL-5–primed eosinophils exhibited chemotaxis toward CCL19 and CCL21 in a dose-dependent fashion. Upon stimulation with CCL19 or CCL21, IL-5–primed eosinophils demonstrated dose-dependent shape changes with polarization of F-actin and exhibited calcium influxes. Finally, primed eosinophils stimulated with CCL19 or CCL21 exhibited increased phosphorylation of ERK in response to both CCR7 ligands. We demonstrate that human eosinophils express CCR7 and have multipotent responses to the known ligands of CCR7. PMID:23449735

  4. Chemokine receptor CCR5 in interferon-treated multiple sclerosis

    DEFF Research Database (Denmark)

    Sellebjerg, F; Kristiansen, Thomas Birk; Wittenhagen, P

    2007-01-01

    OBJECTIVE: To study the relationship between CC chemokine receptor CCR5 expression and disease activity in multiple sclerosis (MS) patients treated with beta-interferon (IFN-beta). METHODS: The CCR5 Delta32 allele and a CCR5 promoter polymorphism associated with cell surface expression of CCR5 were...

  5. Influence of the CCR2-V64I Polymorphism on Human Immunodeficiency Virus Type 1 Coreceptor Activity and on Chemokine Receptor Function of CCR2b, CCR3, CCR5, and CXCR4

    OpenAIRE

    Lee, Benhur; Doranz, Benjamin J.; Rana, Shalini; Yi, Yanji; Mellado, Mario; Frade, Jose M. R.; Martinez-A., Carlos; O’Brien, Stephen J.; Dean, Michael; Collman, Ronald G.; Doms, Robert W.

    1998-01-01

    The chemokine receptors CCR5 and CXCR4 are used by human immunodeficiency virus type 1 (HIV-1) in conjunction with CD4 to infect cells. In addition, some virus strains can use alternative chemokine receptors, including CCR2b and CCR3, for infection. A polymorphism in CCR2 (CCR2-V64I) is associated with a 2- to 4-year delay in the progression to AIDS. To investigate the mechanism of this protective effect, we studied the expression of CCR2b and CCR2b-V64I, their chemokine and HIV-1 coreceptor ...

  6. Why CCR2 and CCR5 blockade failed and why CCR1 blockade might still be effective in the treatment of rheumatoid arthritis

    OpenAIRE

    Lebre, M.C.; Vergunst, C.E.; Choi, I.Y.K.; Aarrass, S.; Oliveira, A.S.F.; Wyant, T.; Horuk, R.; Reedquist, K.A.; Tak, P.P.

    2011-01-01

    BACKGROUND: The aim of this study was to provide more insight into the question as to why blockade of CCR1, CCR2, and CCR5 may have failed in clinical trials in rheumatoid arthritis (RA) patients, using an in vitro monocyte migration system model. METHODOLOGY/PRINCIPAL FINDINGS: Monocytes from healthy donors (HD; n = 8) or from RA patients (for CCR2 and CCR5 antibody n = 8; for CCR1 blockade n = 13) were isolated from peripheral blood and pre-incubated with different concentrations of either ...

  7. Increased frequency of CCR4+ and CCR6+ memory T-cells including CCR7+CD45RAmed very early memory cells in granulomatosis with polyangiitis (Wegener's)

    OpenAIRE

    Fagin, Ursula; Pitann, Silke; Gross, Wolfgang L; Lamprecht, Peter

    2012-01-01

    Introduction Chemokine receptors play an important role in mediating the recruitment of T cells to inflammatory sites. Previously, small proportions of circulating Th1-type CCR5+ and Th2-type CCR3+ cells have been shown in granulomatosis with polyangiitis (GPA). Wondering to what extent CCR4 and CCR6 expression could also be implicated in T cell recruitment to inflamed sites in GPA, we investigated the expression of CCR4 and CCR6 on T cells and its association with T cell diversity and polari...

  8. CCR Magazines | Center for Cancer Research

    Science.gov (United States)

    The Center for Cancer Research (CCR) has two magazines, MILESTONES and LANDMARKS, that highlight our annual advances and top contributions to the understanding, detection, treatment and prevention of cancer over the years.

  9. CCR7 signaling pathway and retinal neovascularization

    Directory of Open Access Journals (Sweden)

    Lin-Hui Yuan

    2015-11-01

    Full Text Available Retinal neovascularization diseases are the major causes of blindness. C-C chemokine receptor type 7(CCR7can promote the expression of vascular endothelial growth factor(VEGFthrough the extracellular signal regulated kinase(ERKpathway, leading to vascular leakage, proliferation of vascular endothelial cell, neovascularization and etc. The detection of CCR7 can guide the diagnosis and treatments of retinal neovascularization diseases.

  10. CCR3, CCR5, CCR8 and CXCR3 expression in memory T helper cells from allergic rhinitis patients, asymptomatically sensitized and healthy individuals

    DEFF Research Database (Denmark)

    Holse, Mille; Assing, Kristian; Poulsen, Lars K.

    2006-01-01

    Chemokine receptors have been suggested to be preferentially expressed on CD4+ T cells with CCR3 and CCR8 linked to the T helper (Th) 2 subset and CCR5 and CXCR3 to the Th1 subset, however this remains controversial....

  11. Extracellular Disulfide Bridges Serve Different Purposes in Two Homologous Chemokine Receptors, CCR1 and CCR5

    DEFF Research Database (Denmark)

    Rummel, Pia Cwarzko; Thiele, Stefanie; Hansen, Laerke Smidt

    2013-01-01

    interact with residues in the main binding crevice, we show that the 7TM-conserved bridge is essential for all types of ligand-mediated activation, whereas the chemokine-conserved bridge is dispensable for small-molecule activation in CCR1. However, in striking contrast to previous studies in other...... chemokine receptors, high affinity CCL3 chemokine binding was maintained in the absence of either bridge. In CCR5, the closest homolog to CCR1, a completely different dependency was observed as neither chemokine activation nor binding was retained in the absence of either bridge. In contrast, both bridges...... where dispensable for small-molecule activation. This indicates that CCR5 activity is independent of extracellular regions, whereas in CCR1, preserved folding of ECL2 is necessary for activation. These results indicate that conserved structural features in a receptor subgroup, does not necessarily...

  12. CCL5, CCR1 and CCR5 in murine glioblastoma: immune cell infiltration and survival rates are not dependent on individual expression of either CCR1 or CCR5

    OpenAIRE

    Pham, Kien; Luo, Defang; Liu, Che; Harrison, Jeffrey K.

    2012-01-01

    Glioblastoma multiforme (GBM) is the most malignant brain tumor. Microglia/macrophages are found within human GBM where they likely promote tumor progression. We report that CCL5, CCR1, and CCR5 are expressed in glioblastoma. Individual deletion of CCR1 or CCR5 had little to no effect on survival of tumor bearing mice, or numbers of glioblastoma-infiltrated microglia/macrophages or lymphocytes. CCL5 promoted in vitro migration of wild type, CCR1- or CCR5-deficient microglia/macrophages that w...

  13. Detectable perfusion changes in MAG3 studies

    International Nuclear Information System (INIS)

    Shuter, B.; Bernar, A.; Roach, P.

    1998-01-01

    Full text: The use of 120 MBq 99m Tc-MAG 3 instead of 600 MBq 99m Tc-DTPA in renal imaging has degraded the images obtained during the perfusion phase. An increase of the minimum detectable change (MDC) in blood flow (BF) would also be expected. In transplant patients, renal BF is an important factor in patient management and the MDC should be small to allow early detection of reduced perfusion. We determined the mean and coefficient of variation (CoV: standard deviation/mean) of three renal perfusion indices as a function of counts in the time-activity curves (TACs). Transplant patients were given a dose of about 300 MBq of 99m Tc-MAG3 and images acquired at 8 fps for 60s. TACs made up from 8, 4, 2 or I images per second allowed calculation of renal perfusion indices as if doses of 300, 150, 75 and 38 MBq had been administered. Perfusion indices based on area under the TACs up to the arterial peak (API), the maximum slopes of the TACs (SPI) and the maximum slope of renal TAC and height of arterial TAC (BPI) were calculated by our routine renal software package. As the administered dose decreased, the CoV rose for all indices, least for BPI and most for API. BPI CoV increased from ∼10% at 300 MBq to 20% at 75 MBq, but API CoV rose from 6% to 46%. Mean BPI was stable over the dose range, but mean API showed a systematic increase of about 50% over the 300 MBq result. We conclude that at 120 MBq the MDC (expressed as 2*CoV) in BF is 30-60%, whereas at 600 MBq it may be as low as 10%, allowing earlier confident detection of a change in BF. The BPI was the preferred perfusion index as its mean value changed little and it had the least CoV at lower activities. The data also imply that relative kidney perfusion in the one individual will be much less accurate with 120 MBq of MAG 3

  14. CCR Interns | Center for Cancer Research

    Science.gov (United States)

    The Cancer Research Interns (CRI) Summer Program was inaugurated in 2004 to provide an open door for students looking for an initial training opportunity. The goal is to enhance diversity within the CCR (Center for Cancer Research) training program and we have placed 338 students from 2004 to 2017, in labs and branches across the division.  The CCR and the Center for Cancer Training’s Office of Training and Education provide stipend support, some Service & Supply funds, and travel support for those students who meet the financial eligibility criteria (

  15. Bohunice V1 NPP upgrading programme

    International Nuclear Information System (INIS)

    Kerak, J.

    2001-01-01

    The paper describes whole process of Bohunice V1 NPP nuclear safety and operational reliability level increase which has been performed since units commissioning (1. unit in 1978, 2. unit in 1980), continued Small Reconstruction (1991 -1993) and finished Gradual Upgrading(1994 -2000). The main purpose is to last stage -Gradual upgrading of Bohunice V1 NPP. (author)

  16. De moeder mag zeggen waar ze haar baby krijgt

    NARCIS (Netherlands)

    Kingma, E.M.

    2012-01-01

    Soms nemen aanstaande moeders beslissingen die niet in het belang van hun aanstaande kind lijken te zijn. Zoals thuis willen bevallen bij een stuitligging of een tweeling. Mag dat? Ja, dat mag. Zelfs als dat betekent dat de aanstaande baby een groot risico loopt om dood te gaan of blijvende schade

  17. Mathematical Modeling of Metal Active Gas (MAG) Arc Welding

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    In the present paper, a numerical model for MAG (metal active gas) arc welding of thin plate has been developed. In MAG arc welding, the electrode wire is melted and supplied into the molten pool intermittently. Accordingly, it is assumed on the modeling that the thermal energy enters the base-plates through two following mechanisms, i.e., direct heating from arc plasma and “indirect” heating from the deposited metal. In the second part of the paper, MAG arc welding process is numerically analyzed by using the model, and the calculated weld bead dimension and surface profile have been compared with the experimental MAG welds on steel plate. As the result, it is made clear that the model is capable of predicting the bead profile of thin-plate MAG arc welding , including weld bead with undercutting.

  18. CrowdMag - Crowdsourcing magnetic data

    Science.gov (United States)

    Nair, M. C.; Boneh, N.; Chulliat, A.

    2014-12-01

    In the CrowdMag project, we explore whether digital magnetometers built in modern mobile phones can be used as scientific instruments to measure Earth's magnetic field. Most modern mobile phones have digital magnetometers to orient themselves. A phone's magnetometer measures three components of the local magnetic field with a typical sensitivity of about 150 to 600 nanotesla (nT). By combining data from vector magnetometers and accelerometers, phone's orientation is determined. Using phone's Internet connection, magnetic data and location are sent to a central server. At the server, we check quality of the magnetic data from all users and make the data available to the public as aggregate maps. We have two long-term goals. 1) Develop near-real-time models of Earth's time changing magnetic field by reducing man-made noise from crowdsourced data and combining it with geomagnetic data from other sources. 2) Improving accuracy of magnetic navigation by mapping magnetic noise sources (for e.g. power transformer and iron pipes). Key challenges to this endeavor are the low sensitivity of the phone's magnetometer and the noisy environment within and surrounding the phone. URL : http://www.ngdc.noaa.gov/geomag/crowdmag.shtml

  19. GRIP HURRICANE IMAGING RADIOMETER (HIRAD) V1

    Data.gov (United States)

    National Aeronautics and Space Administration — The GRIP Hurricane Imaging Radiometer (HIRAD) V1 dataset contains measurements of brightness temperature taken at 4, 5, 6 and 6.6 GHz, as well as MERRA 2 m wind...

  20. USEEIO v1.1 - Matrices

    Data.gov (United States)

    U.S. Environmental Protection Agency — This dataset provides the basic building blocks for the USEEIO v1.1 model and life cycle results per $1 (2013 USD) demand for all goods and services in the model in...

  1. Heterogeneity of Polyneuropathy Associated with Anti-MAG Antibodies

    Directory of Open Access Journals (Sweden)

    Laurent Magy

    2015-01-01

    Full Text Available Polyneuropathy associated with IgM monoclonal gammopathy and anti-myelin associated glycoprotein (MAG antibodies is an immune-mediated demyelinating neuropathy. The pathophysiology of this condition is likely to involve anti-MAG antibody deposition on myelin sheaths of the peripheral nerves and it is supposed to be distinct from chronic inflammatory demyelinating neuropathy (CIDP, another immune-mediated demyelinating peripheral neuropathy. In this series, we have retrospectively reviewed clinical and laboratory findings from 60 patients with polyneuropathy, IgM gammopathy, and anti-MAG antibodies. We found that the clinical picture in these patients is highly variable suggesting a direct link between the monoclonal gammopathy and the neuropathy. Conversely, one-third of patients had a CIDP-like phenotype on electrodiagnostic testing and this was correlated with a low titer of anti-MAG antibodies and the absence of widening of myelin lamellae. Our data suggest that polyneuropathy associated with anti-MAG antibodies is less homogeneous than previously said and that the pathophysiology of the condition is likely to be heterogeneous as well with the self-antigen being MAG in most of the patients but possibly being another component of myelin in the others.

  2. Safety upgrading of Bohunice V1 NPP

    International Nuclear Information System (INIS)

    2001-01-01

    This CD is multimedia presentation of programme safety upgrading of Bohunice V1 NPP. It consist of next chapters: (1) Introductory speeches; (2) Nuclear power plant WWER 440; (3) Safety improvement; (4) Bohunice Nuclear power plants subsidiary; (5) Siemens; (6) REKON; (7) VUJE Trnava, Inc. - Engineering, Design and Research Organisation; (8) Album

  3. Analysis of Staphylococcal cassette chromosome mec in Staphylococcus haemolyticus and Staphylococcus sciuri: identification of a novel ccr gene complex with a newly identified ccrA allotype (ccrA7).

    Science.gov (United States)

    Urushibara, Noriko; Paul, Shyamal Kumar; Hossain, Mohammad Akram; Kawaguchiya, Mitsuyo; Kobayashi, Nobumichi

    2011-06-01

    Methicillin resistance in staphylococci is conferred by the acquisition in its chromosome of the mecA gene, which is located on a mobile genetic element called staphylococcal cassette chromosome mec (SCCmec). Genetic type of SCCmec is defined by combination of mec gene complex class and cassette chromosome recombinase gene (ccr) allotype. In this study, we analyzed genetic diversity of the SCCmec in 11 Staphylococcus haemolyticus strains and a Staphylococcus sciuri strain, which were recently isolated from clinical specimens in Bangladesh. Among these strains, only two S. haemolyticus strains were proved to have the known types of SCCmec, that is, SCCmec V (class C2 mec-ccrC) and VII (class C1 mec-ccrC). Five S. haemolyticus strains were assigned two unique mec-ccr gene complexes combination; that is, class C1 mec-ccrA4B4 (four isolates) and class A mec-ccrC (one isolate). In the remaining four S. haemolyticus strains with class C1 mec, no known ccr allotypes could be detected. A single S. sciuri strain with class A mec complex carried a ccrA gene belonging to a novel allotype designated ccrA7, together with ccrB3. The ccrA7 gene in the S. sciuri strain showed 61.7%-82.7% sequence identity to the ccrA gene sequences published so far, and 75.3% identity to ccrA3, which is a component of the type 3 ccr complex (ccrA3-ccrB3) in methicillin-resistant Staphylococcus aureus. The results of the present study indicated that mec gene complex and ccr genes in coagulase-negative staphylococci are highly divergent, and distinct from those of common methicillin-resistant S. aureus. Identification of the novel ccrA7 allotype combined with ccrB3 suggested an occurrence of recombination between different ccr complexes in nature.

  4. Welding of Low Alloy Steel DIN 15Mo3 by MIG/MAG Spot

    OpenAIRE

    Nabeel K. Abid Al- Sahib

    2006-01-01

    ????? ????? ????? ????? ??????? ?????? ?? ????? ?????? ?????? ?????? ??????? ?????? ?????? (MIG/MAG spot) ???????? ??? ??????? ????? ?? ???? ???????? ????? ??? ???????? ?? ?????? ??????????? ??????? ???????? ????? ???? ??????? ??????? ????? ??? (DIN15Mo3) ?????? ?????? ?????? ?????? ?????? ?? ???? ???? ?????? ???????" ??? ?????? ??? ????. ????? ??????? ??????? ?????? ??? CO2 ????" ?? ??? ??????? ?? ???? ??????? ??????? ????? ?? ?????? ????? ?? ??? ???? ?? ????? (13%) ???? (4mm) ???? (2sec). ?...

  5. On relativistic irreducible quantum fields fulfilling CCR

    International Nuclear Information System (INIS)

    Baumann, K.

    1987-01-01

    Let phi be a relativistic scalar field fulfilling canonical commutation relations (CCR). Furthermore it is assumed that the time zero fields and momenta form an irreducible set. Based on estimates given by Herbst [I. W. Herbst, J. Math. Phys. 17, 1210 (1976)], and by methods developed by Powers [R. T. Powers, Commun. Math. Phys. 4, 145 (1967)], it is shown that phi has to be a free field in n>3 space dimensions. For n = 3 (resp. n = 2) restrictions that look similar to the restriction in a formal :phi 4 : 3 /sub +/ 1 (resp. :phi 6 : 2 /sub +/ 1 ) theory are obtained

  6. V1 mechanisms underlying chromatic contrast detection

    Science.gov (United States)

    Hass, Charles A.

    2013-01-01

    To elucidate the cortical mechanisms of color vision, we recorded from individual primary visual cortex (V1) neurons in macaque monkeys performing a chromatic detection task. Roughly 30% of the neurons that we encountered were unresponsive at the monkeys' psychophysical detection threshold (PT). The other 70% were responsive at threshold but on average, were slightly less sensitive than the monkey. For these neurons, the relationship between neurometric threshold (NT) and PT was consistent across the four isoluminant color directions tested. A corollary of this result is that NTs were roughly four times lower for stimuli that modulated the long- and middle-wavelength sensitive cones out of phase. Nearly one-half of the neurons that responded to chromatic stimuli at the monkeys' detection threshold also responded to high-contrast luminance modulations, suggesting a role for neurons that are jointly tuned to color and luminance in chromatic detection. Analysis of neuronal contrast-response functions and signal-to-noise ratios yielded no evidence for a special set of “cardinal color directions,” for which V1 neurons are particularly sensitive. We conclude that at detection threshold—as shown previously with high-contrast stimuli—V1 neurons are tuned for a diverse set of color directions and do not segregate naturally into red–green and blue–yellow categories. PMID:23446689

  7. METEOR v1.0 - User's Guide

    International Nuclear Information System (INIS)

    Palomo, E.

    1994-01-01

    This script is a User's Guide for the software package METEOR for statistical analysis of meteorological data series. The original version of METEOR have been developed by Ph.D. Elena Palomo, CIEMAT-IER, GIMASE. It is built by linking programs and routines written in FORTRAN 77 and it adds the graphical capabilities of GNUPLOT. The shape of this toolbox was designed following the criteria of modularity, flexibility and agility criteria. All the input, output and analysis options are structured in three main menus: i) the first is aimed to evaluate the quality of the data set; ii) the second is aimed for pre-processing of the data; and iii) the third is aimed towards the statistical analyses and for creating the graphical outputs. Actually the information about METEOR is constituted by three documents written in spanish: 1) METEOR v1.0: User's guide; 2) METEOR v1.0: A usage example; 3) METEOR v1.0: Design and structure of the software package. (Author)

  8. Allosteric and orthosteric sites in CC chemokine receptor (CCR5), a chimeric receptor approach

    DEFF Research Database (Denmark)

    Thiele, Stefanie; Steen, Anne; Jensen, Pia C

    2011-01-01

    -allosteric molecules. A chimera was successfully constructed between CCR5 and the closely related CCR2 by transferring all extracellular regions of CCR2 to CCR5, i.e. a Trojan horse that resembles CCR2 extracellularly but signals through a CCR5 transmembrane unit. The chimera bound CCR2 (CCL2 and CCL7), but not CCR5...... preserved, the allosteric enhancement of chemokine binding was disrupted. In summary, the Trojan horse chimera revealed that orthosteric and allosteric sites could be structurally separated and still act together with transmission of agonism and antagonism across the different receptor units....

  9. The ins and outs of ligand binding to CCR2

    NARCIS (Netherlands)

    Zweemer, Annelien Jacomina Maria

    2014-01-01

    This thesis provides novel insights in the molecular mechanism of action of antagonists for the chemokine receptor CCR2. CCR2 belongs to the protein family of G protein-coupled receptors (GPCRs). It is involved in several inflammatory diseases and therefore many small molecule antagonists targeting

  10. Downregulation of CCR1 inhibits human hepatocellular carcinoma cell invasion

    International Nuclear Information System (INIS)

    Wu Xiaofeng; Fan Jia; Wang Xiaoying; Zhou Jian; Qiu Shuangjian; Yu Yao; Liu Yinkun; Tang Zhaoyou

    2007-01-01

    CC chemokine receptor 1 (CCR1) has an important role in the recruitment of leukocytes to the site of inflammation. The migration and metastasis of tumor cells shares many similarities with leukocyte trafficking, which is mainly regulated by chemokine receptor-ligand interactions. CCR1 is highly expressed in hepatocellular carcinoma (HCC) cells and tissues with unknown functions. In this study, we silenced CCR1 expression in the human HCC cell line HCCLM3 using artificial microRNA (miRNA)-mediated RNA interference (RNAi) and examined the invasiveness and proliferation of CCR1-silenced HCCLM3 cells and the matrix metalloproteinase (MMP) activity. The miRNA-mediated knockdown expression of CCR1 significantly inhibited the invasive ability of HCCLM3 cells, but had only a minor effect on the cellular proliferation rate. Moreover, CCR1 knockdown significantly reduced the secretion of MMP-2. Together, these findings indicate that CCR1 has an important role in HCCLM3 invasion and that CCR1 might be a new target of HCC treatment

  11. Chemokine receptor CCR5 in interferon-treated multiple sclerosis

    DEFF Research Database (Denmark)

    Sellebjerg, F; Kristiansen, T B; Wittenhagen, P

    2007-01-01

    To study the relationship between CC chemokine receptor CCR5 expression and disease activity in multiple sclerosis (MS) patients treated with beta-interferon (IFN-beta).......To study the relationship between CC chemokine receptor CCR5 expression and disease activity in multiple sclerosis (MS) patients treated with beta-interferon (IFN-beta)....

  12. CCR presentations at AACR - 2018 | Center for Cancer Research

    Science.gov (United States)

    CCR presentations at AACR Several CCR scientists will present their research at the AACR Annual Meeting in Chicago, IL, between April 14-18, 2018. Selected oral presentations are listed below. A full list of abstracts can be found on the AACR website.

  13. CCR presentations at AACR | Center for Cancer Research

    Science.gov (United States)

    CCR presentations at AACR Several CCR scientists will present their research at the AACR Annual Meeting in Washington, D.C., between April 1-5, 2017. Selected oral presentations are listed below. A full list of abstracts can be found on the AACR website.

  14. A Simplified Technique for Evaluating Human "CCR5" Genetic Polymorphism

    Science.gov (United States)

    Falteisek, Lukáš; Cerný, Jan; Janštová, Vanda

    2013-01-01

    To involve students in thinking about the problem of AIDS (which is important in the view of nondecreasing infection rates), we established a practical lab using a simplified adaptation of Thomas's (2004) method to determine the polymorphism of HIV co-receptor CCR5 from students' own epithelial cells. CCR5 is a receptor involved in inflammatory…

  15. Phenotypic expressions of CCR5-Delta 32/Delta 32 homozygosity

    NARCIS (Netherlands)

    Nguyen, GT; Carrington, M; Beeler, JA; Dean, M; Aledort, LM; Blatt, PM; Cohen, AR; DiMichele, D; Eyster, ME; Kessler, CM; Konkle, B; Leissinger, C; Luban, N; O'Brien, SJ; Goedert, JJ; O'Brien, TR

    1999-01-01

    Objective: As blockade of CC-chemokine receptor 5 (CCR5) has been proposed as therapy for HIV-1, we examined whether the CCR5-Delta 32/Delta 32 homozygous genotype has phenotypic expressions other than those related to HIV-1. Design: Study subjects were white homosexual men or men with hemophilia

  16. MagLev Cobra: Test Facilities and Operational Experiments

    International Nuclear Information System (INIS)

    Sotelo, G G; Dias, D H J N; De Oliveira, R A H; Ferreira, A C; De Andrade, R Jr; Stephan, R M

    2014-01-01

    The superconducting MagLev technology for transportation systems is becoming mature due to the research and developing effort of recent years. The Brazilian project, named MagLev-Cobra, started in 1998. It has the goal of developing a superconducting levitation vehicle for urban areas. The adopted levitation technology is based on the diamagnetic and the flux pinning properties of YBa 2 Cu 3 O 7−δ (YBCO) bulk blocks in the interaction with Nd-Fe-B permanent magnets. A laboratory test facility with permanent magnet guideway, linear induction motor and one vehicle module is been built to investigate its operation. The MagLev-Cobra project state of the art is presented in the present paper, describing some construction details of the new test line with 200 m.

  17. MagLev Cobra: Test Facilities and Operational Experiments

    Science.gov (United States)

    Sotelo, G. G.; Dias, D. H. J. N.; de Oliveira, R. A. H.; Ferreira, A. C.; De Andrade, R., Jr.; Stephan, R. M.

    2014-05-01

    The superconducting MagLev technology for transportation systems is becoming mature due to the research and developing effort of recent years. The Brazilian project, named MagLev-Cobra, started in 1998. It has the goal of developing a superconducting levitation vehicle for urban areas. The adopted levitation technology is based on the diamagnetic and the flux pinning properties of YBa2Cu3O7-δ (YBCO) bulk blocks in the interaction with Nd-Fe-B permanent magnets. A laboratory test facility with permanent magnet guideway, linear induction motor and one vehicle module is been built to investigate its operation. The MagLev-Cobra project state of the art is presented in the present paper, describing some construction details of the new test line with 200 m.

  18. Oral CCR5 inhibitors: will they make it through?

    Science.gov (United States)

    Biswas, Priscilla; Nozza, Silvia; Scarlatti, Gabriella; Lazzarin, Adriano; Tambussi, Giuseppe

    2006-05-01

    The therapeutic armamentarium against HIV has recently gained a drug belonging to a novel class of antiretrovirals, the entry inhibitors. The last decade has driven an in-depth knowledge of the HIV entry process, unravelling the multiple engagements of the HIV envelope proteins with the cellular receptorial complex that is composed of a primary receptor (CD4) and a co-receptor (CCR5 or CXCR4). The vast majority of HIV-infected subjects exhibit biological viral variants that use CCR5 as a co-receptor. Individuals with a mutated CCR5 gene, both homo- and heterozygotes, appear to be healthy. For these and other reasons, CCR5 represents an appealing target for treatment intervention, although certain challenges can not be ignored. Promising small-molecule, orally bioavailable CCR5 antagonists are under development for the treatment of HIV-1 infection.

  19. Micro-jet Cooling by Compressed Air after MAG Welding

    Directory of Open Access Journals (Sweden)

    Węgrzyn T.

    2016-06-01

    Full Text Available The material selected for this investigation was low alloy steel weld metal deposit (WMD after MAG welding with micro-jet cooling. The present investigation was aimed as the following tasks: analyze impact toughness of WMD in terms of micro-jet cooling parameters. Weld metal deposit (WMD was first time carried out for MAG welding with micro-jet cooling of compressed air and gas mixture of argon and air. Until that moment only argon, helium and nitrogen and its gas mixture were tested for micro-jet cooling.

  20. Micro-jet Cooling by Compressed Air after MAG Welding

    OpenAIRE

    Węgrzyn T.; Piwnik J.; Tarasiuk W.; Stanik Z.; Gabrylewski M.

    2016-01-01

    The material selected for this investigation was low alloy steel weld metal deposit (WMD) after MAG welding with micro-jet cooling. The present investigation was aimed as the following tasks: analyze impact toughness of WMD in terms of micro-jet cooling parameters. Weld metal deposit (WMD) was first time carried out for MAG welding with micro-jet cooling of compressed air and gas mixture of argon and air. Until that moment only argon, helium and nitrogen and its gas mixture were tested for mi...

  1. Radioactive Waste Decontamination Using Selentec Mag*SepSM Particles

    International Nuclear Information System (INIS)

    Walker, D.D.

    1998-01-01

    A sorbent containing crystalline silicotitanate (CST) tested for cesium removal from simulated Savannah River Site (SRS) soluble high activity waste showed rapid kinetics (1 h contact time) and high distribution coefficients (Kd 4000 mL/g of CST). The sorbent was prepared by Selective Environmental Technologies, Inc., (Selentec) as a MAG*SEP particle containing CST obtained from the Molecular Sieve Department of UOP, LLC, Results of preliminary tests suggest potential applications of the Selentec MAG*SEP particles to radioactive waste decontamination at SRS

  2. CCR2+ and CCR5+ CD8+ T cells increase during viral infection and migrate to sites of infection

    DEFF Research Database (Denmark)

    Nansen, A; Marker, O; Bartholdy, C

    2000-01-01

    Chemokines and their receptors play a critical role in the selective recruitment of various leukocyte subsets. In this study, we correlated the expression of multiple chemokine and CC chemokine receptor (CCR) genes during the course of intracerebral (i.c.) infection with lymphocytic choriomeningi......Chemokines and their receptors play a critical role in the selective recruitment of various leukocyte subsets. In this study, we correlated the expression of multiple chemokine and CC chemokine receptor (CCR) genes during the course of intracerebral (i.c.) infection with lymphocytic...... a rapidly lethal, T cell-independent encephalitis, and infection resulted in a dramatic early up-regulation of chemokine gene expression. Similar marked up-regulation of chemokine expression was not seen until late after LCMV infection and required the presence of activated T cells. Cerebral CCR gene...... expression was dominated by CCR1, CCR2 and CCR5. However, despite a stronger initial chemokine signal in VSV-infected mice, only LCMV-induced T cell-dependent inflammation was found to be associated with substantially increased expression of CCR genes. Virus-activated CD8+ T cells were found to express CCR2...

  3. Systemic MCP1/CCR2 blockade and leukocyte specific MCP1/CCR2 inhibition affect aortic aneurysm formation differently

    NARCIS (Netherlands)

    de Waard, Vivian; Bot, Ilze; de Jager, Saskia C. A.; Talib, Sara; Egashira, Kensuke; de Vries, Margreet R.; Quax, Paul H. A.; Biessen, Erik A. L.; van Berkel, Theo J. C.

    2010-01-01

    Objective: CCR2, the receptor for monocyte chemoattractant protein 1 (MCP1), is involved in atherosclerosis and abdominal aortic aneurysms (AAAs). Here, we explored the potential beneficial blockade of the MCP1/CCR2 pathway. Methods: We applied an AAA model in aging apolipoprotein E deficient mice

  4. Role of the chemokine receptors CCR1, CCR2 and CCR4 in the pathogenesis of experimental dengue infection in mice.

    Directory of Open Access Journals (Sweden)

    Rodrigo Guabiraba

    Full Text Available Dengue virus (DENV, a mosquito-borne flavivirus, is a public health problem in many tropical countries. Recent clinical data have shown an association between levels of different chemokines in plasma and severity of dengue. We evaluated the role of CC chemokine receptors CCR1, CCR2 and CCR4 in an experimental model of DENV-2 infection in mice. Infection of mice induced evident clinical disease and tissue damage, including thrombocytopenia, hemoconcentration, lymphopenia, increased levels of transaminases and pro-inflammatory cytokines, and lethality in WT mice. Importantly, infected WT mice presented increased levels of chemokines CCL2/JE, CCL3/MIP-1α and CCL5/RANTES in spleen and liver. CCR1⁻/⁻ mice had a mild phenotype with disease presentation and lethality similar to those of WT mice. In CCR2⁻/⁻ mice, lethality, liver damage, levels of IL-6 and IFN-γ, and leukocyte activation were attenuated. However, thrombocytopenia, hemoconcentration and systemic TNF-α levels were similar to infected WT mice. Infection enhanced levels of CCL17/TARC, a CCR4 ligand. In CCR4⁻/⁻ mice, lethality, tissue injury and systemic inflammation were markedly decreased. Despite differences in disease presentation in CCR-deficient mice, there was no significant difference in viral load. In conclusion, activation of chemokine receptors has discrete roles in the pathogenesis of dengue infection. These studies suggest that the chemokine storm that follows severe primary dengue infection associates mostly to development of disease rather than protection.

  5. Experience of Bohunice V-1 NPP

    International Nuclear Information System (INIS)

    Dobik, Dobroslav

    2000-01-01

    Slovakia remains significantly dependent on imports of primary energy sources, which represent as much as 80% of the demand. Of the total consumption of electricity in Slovakia, 40% was generated in nuclear power plant units in 1998. Slovakia operates 6 units with WWER 440 nuclear reactors. Slovakia is the signatory of all important international agreements and conventions in the field of nuclear energy, and its legislation is in an advanced stage of approximation to European Union law. This is a very important aspect, showing Slovakia's approach to nuclear safety. In 1993 Slovakia accepted the commitments of the UN Convention on Climate Changes, including a reduction of greenhouse gases to 1990 levels by the year 2000. Moreover, as an internal target Slovakia has set the reaching of the 'Toronto Objective', i.e. 20% reduction in CO x , emissions through the year 2005 as compared to 1988. In our opinion, this is not possible without nuclear energy. Time has shown, that the political aspects are more powerful, especially if you underestimate their importance over the than the technical ones. In the case of Bohunice V-1 NPP the political aspects were on the following levels: 1. Slovak republic (Czechoslovakia), political changes, decisions of the government; 2. European Union - Agenda 2000, Accession criteria, nuclear safety criteria, EBRD; 3. Austria as a neighbouring country. Starting with year 1990, 23 expert missions took place at Bohunice V-1 NPP by now. The only criteria for further operation should have been Nuclear safety, which is supervised by NRA SR. It was fully in compliance with EU policy, each country is solely responsible for its energy sector and for nuclear energy use. Our satisfaction lasted not too long. Following negotiation with EU on the highest political level, driven by willingness to be invited for negotiation of accession on the Helsinki Summit, the Slovak government decided on September 14th, on Bohunice V-1 Units shutdown in 2006 and 2008

  6. Roles of CcrA and CcrB in Excision and Integration of Staphylococcal Cassette Chromosome mec, a Staphylococcus aureus Genomic Island▿

    OpenAIRE

    Wang, Lei; Archer, Gordon L.

    2010-01-01

    The gene encoding resistance to methicillin and other β-lactam antibiotics in staphylococci, mecA, is carried on a genomic island, SCCmec (for staphylococcal cassette chromosome mec). The chromosomal excision and integration of types I to IV SCCmec are catalyzed by the site-specific recombinases CcrA and CcrB, the genes for which are encoded on each element. We sought to identify the relative contributions of CcrA and CcrB in the excision and integration of SCCmec. Purified CcrB but not CcrA ...

  7. Cloning and expression analysis of cinnamoyl-CoA reductase (CCR) genes in sorghum.

    Science.gov (United States)

    Li, Jieqin; Fan, Feifei; Wang, Lihua; Zhan, Qiuwen; Wu, Peijin; Du, Junli; Yang, Xiaocui; Liu, Yanlong

    2016-01-01

    Cinnamoyl-CoA reductase (CCR) is the first enzyme in the monolignol-specific branch of the lignin biosynthetic pathway. In this research, three sorghum CCR genes including SbCCR1, SbCCR2-1 and SbCCR2-2 were cloned and characterized. Analyses of the structure and phylogeny of the three CCR genes showed evolutionary conservation of the functional domains and divergence of function. Transient expression assays in Nicotiana benthamiana leaves demonstrated that the three CCR proteins were localized in the cytoplasm. The expression analysis showed that the three CCR genes were induced by drought. But in 48 h, the expression levels of SbCCR1 and SbCCR2-2 did not differ between CK and the drought treatment; while the expression level of SbCCR2-1 in the drought treatment was higher than in CK. The expression of the SbCCR1 and SbCCR2-1 genes was not induced by sorghum aphid [Melanaphis sacchari (Zehntner)] attack, but SbCCR2-2 was significantly induced by sorghum aphid attack. It is suggested that SbCCR2-2 is involved in the process of pest defense. Absolute quantitative real-time PCR revealed that the three CCR genes were mainly expressed in lignin deposition organs. The gene copy number of SbCCR1 was significantly higher than those of SbCCR2-1 and SbCCR2-2 in the tested tissues, especially in stem. The results provide new insight into the functions of the three CCR genes in sorghum.

  8. The chemokine receptor CCR5 in the central nervous system.

    Science.gov (United States)

    Sorce, Silvia; Myburgh, Renier; Krause, Karl-Heinz

    2011-02-01

    The expression and the role of the chemokine receptor CCR5 have been mainly studied in the context of HIV infection. However, this protein is also expressed in the brain, where it can be crucial in determining the outcome in response to different insults. CCR5 expression can be deleterious or protective in controlling the progression of certain infections in the CNS, but it is also emerging that it could play a role in non-infectious diseases. In particular, it appears that, in addition to modulating immune responses, CCR5 can influence neuronal survival. Here, we summarize the present knowledge about the expression of CCR5 in the brain and highlight recent findings suggesting its possible involvement in neuroprotective mechanisms. Copyright © 2011. Published by Elsevier Ltd.

  9. Relevance of CCL3/CCR5 axis in oral carcinogenesis.

    Science.gov (United States)

    da Silva, Janine Mayra; Moreira Dos Santos, Tálita Pollyanna; Sobral, Lays Martin; Queiroz-Junior, Celso Martins; Rachid, Milene Alvarenga; Proudfoot, Amanda E I; Garlet, Gustavo Pompermaier; Batista, Aline Carvalho; Teixeira, Mauro Martins; Leopoldino, Andréia Machado; Russo, Remo Castro; Silva, Tarcília Aparecida

    2017-08-01

    The chemokine CCL3 is a chemotactic cytokine crucial for inflammatory cell recruitment in homeostatic and pathological conditions. CCL3 might stimulate cancer progression by promoting leukocyte accumulation, angiogenesis and tumour growth. The expression of CCL3 and its receptors CCR1 and CCR5 was demonstrated in oral squamous cell carcinoma (OSCC), but their role was not defined. Here, the functions of CCL3 were assessed using a model of chemically induced tongue carcinogenesis with 4-nitroquinoline-1-oxide (4NQO). Lineages of OSCC were used to analyse the effects of CCL3 in vitro . The 4NQO-induced lesions exhibited increased expression of CCL3, CCR1 and CCR5. CCL3 -/- and CCR5 -/- mice presented reduced incidence of tongue tumours compared to wild-type (WT) and CCR1 -/- mice. Consistently, attenuated cytomorphological atypia and reduced cell proliferation were observed in lesions of CCL3 -/- and CCR5 -/- mice. OSCC from CCL3 -/- mice exhibited lower infiltration of eosinophils and reduced expression of Egf, Fgf1, Tgf-β1, Vegfa, Vegfb, Itga-4, Vtn, Mmp-1a, Mmp-2 and Mmp-9 than WT mice. In vitro , CCL3 induced invasion and production of CCL5, IL-6, MMP -2, -8, -9. Blockage of CCL3 in vitro using α-CCL3 or Evasin-1 (a CCL3-binding protein) impaired tumour cell invasion. In conclusion, CCL3/CCR5 axis has pro-tumourigenic effects in oral carcinogenesis. The induction of inflammatory and angiogenic pathways and eosinophils recruitment appear to be the underlying mechanism explaining these effects. These data reveal potential protective effects of CCL3 blockade in oral cancer.

  10. The case for selection at CCR5-Delta32.

    Directory of Open Access Journals (Sweden)

    2005-11-01

    Full Text Available The C-C chemokine receptor 5, 32 base-pair deletion (CCR5-Delta32 allele confers strong resistance to infection by the AIDS virus HIV. Previous studies have suggested that CCR5-Delta32 arose within the past 1,000 y and rose to its present high frequency (5%-14% in Europe as a result of strong positive selection, perhaps by such selective agents as the bubonic plague or smallpox during the Middle Ages. This hypothesis was based on several lines of evidence, including the absence of the allele outside of Europe and long-range linkage disequilibrium at the locus. We reevaluated this evidence with the benefit of much denser genetic maps and extensive control data. We find that the pattern of genetic variation at CCR5-Delta32 does not stand out as exceptional relative to other loci across the genome. Moreover using newer genetic maps, we estimated that the CCR5-Delta32 allele is likely to have arisen more than 5,000 y ago. While such results can not rule out the possibility that some selection may have occurred at C-C chemokine receptor 5 (CCR5, they imply that the pattern of genetic variation seen atCCR5-Delta32 is consistent with neutral evolution. More broadly, the results have general implications for the design of future studies to detect the signs of positive selection in the human genome.

  11. The case for selection at CCR5-Delta32.

    Directory of Open Access Journals (Sweden)

    Pardis C Sabeti

    2005-11-01

    Full Text Available The C-C chemokine receptor 5, 32 base-pair deletion (CCR5-Delta32 allele confers strong resistance to infection by the AIDS virus HIV. Previous studies have suggested that CCR5-Delta32 arose within the past 1,000 y and rose to its present high frequency (5%-14% in Europe as a result of strong positive selection, perhaps by such selective agents as the bubonic plague or smallpox during the Middle Ages. This hypothesis was based on several lines of evidence, including the absence of the allele outside of Europe and long-range linkage disequilibrium at the locus. We reevaluated this evidence with the benefit of much denser genetic maps and extensive control data. We find that the pattern of genetic variation at CCR5-Delta32 does not stand out as exceptional relative to other loci across the genome. Moreover using newer genetic maps, we estimated that the CCR5-Delta32 allele is likely to have arisen more than 5,000 y ago. While such results can not rule out the possibility that some selection may have occurred at C-C chemokine receptor 5 (CCR5, they imply that the pattern of genetic variation seen at CCR5-Delta32 is consistent with neutral evolution. More broadly, the results have general implications for the design of future studies to detect the signs of positive selection in the human genome.

  12. Next Generation HeliMag UXO Mapping Technology

    Science.gov (United States)

    2010-01-01

    Ancillary instrumentation records aircraft height above ground and attitude. A fluxgate magnetometer is used to allow for aeromagnetic compensation of... Magnetometer System WWII World War II WAA wide area assessment ACKNOWLEDGEMENTS This Next Generation HeliMag Unexploded Ordnance (UXO) Mapping...for deployment of seven total-field magnetometers on a Kevlar reinforced boom mounted on a Bell 206L helicopter. The objectives of this

  13. MAG3 in a renal transplant with complications

    International Nuclear Information System (INIS)

    Rynderman, J.

    2002-01-01

    Full text: A 42 year-old female presenting with glomerulonephritis induced end stage renal failure was found suitable for a renal transplant (Tx). A cadaveric renal Tx was performed after a prolonged cold ischaemic time of 12 hours (optimal<4 hours). The surgery was uncomplicated and doppler ultrasound (u/s) post surgery demonstrated good perfusion to the transplant. Sequential MAG3 renal scanning, at days 1, 3 and 5 post transplant demonstrated reduced but clearly identifiable perfusion and an accumulation renogram ('hot kidney') consistent with acute tubular necrosis (ATN). These results lead to a biopsy being performed at day 5. The biopsy demonstrated rejection and tubular dilatation m keeping with ATN Intense anti-rejection therapy commenced. The day 7, MAG3 study demonstrated some improvement in perfusion, uptake, and clearance, however, overall function remained impaired Dialysis was resumed. At day 10, the patient developed pain with a distended, firm, and tender abdomen. An urgent MAG3 study demonstrated acute vascular insult with near complete absence of perfusion or function ('cold kidney') and the decrease on accumulation renogram. Renal u/s demonstrated a peri-nephric haematoma and markedly abnormal intra-renal blood flow in keeping with acute rejection. This lead to an emergency renal Tx nephrectomy Macroscopically, the kidney was swollen with extensive necrosis and surrounded by fresh blood, with microscopy showing extensive rejection and venous thrombosis. Post nephrectomy the patient returned to haemodialysis While limited by ATN in the early post Tx period, MAG3 imaging provided timely, accurate and non invasive diagnostic information as to the viability of the renal Tx and to the ultimate decision to remove the kidney. This case also demonstrates the importance of frequent serial scanning in early post Tx monitoring. Copyright (2002) The Australian and New Zealand Society of Nuclear Medicine Inc

  14. [CCR5, CCR2, apoe, p53, ITGB3 and HFE gene polymorphism in Western Siberia long-livers].

    Science.gov (United States)

    Ivanoshchuk, D E; Mikhaĭlova, S V; Kulikov, I V; Maksimov, V N; Voevoda, M I; Romashchenko, A G

    2012-01-01

    In order to estimate the distribution of some polymorphisms for the CCR5, CCR2, apoE, p53, ITGB3, and HFE genes in Russian long-livers from Western Siberia, a sample of 271 individuals (range 90-105 years) was examined. It was demonstrated that carriage of the delta32 polymorphism for the CCR5 gene, V64/polymorphism for the CCR2 gene, e2/e3/e4 for the apoE gene, L33P for the ITGB3 gene, as well as H63D and S65C polymorphisms for the HFE gene does not influence on predisposition to the longevity; carriage of the 282 Y allele for the HFE gene negatively influences on the longevity; carriage of the heterozygous genotype for the R72P polymorphism for the p53 gene correlates with the longevity of elderly people.

  15. [The expression of periphery blood leucocyte CCR3 and CCR5 in the children with Epstein-Barr virus associated infectious mononucleosis].

    Science.gov (United States)

    Qi, Tie-xiong; Gao, Guo-hua; Liu, Shi-hua

    2010-10-01

    To explore the expression of periphery blood leucocyte CCR3 and CCR5 and to comprehend T helper cell in the Children with Epstein-Barr virus associated infectious mononucleosis. We defined the children according to the diagnosis criterion through Paul-Bunnell test inspecting the children's periphery blood unusual lymphocyte and detecting their anti-EBV-CA-IgM, anti-EBV-CA-IgG and anti-EBV-NA-IgG by ELISA and counted the ratio of CCR3 + and CCR5 + cells in lymphocytes with flow cytometry. The ratio of unusual lymphocyte in IM was higher than that of the healthy control group (P < 0.05). The ratio of CCR3 + cells in IM group was higher than that of the healthy control group (P < 0.05). The ratio of CCR5 + cells in IM group was significantly lower than that of the healthy control group. CCR3 + had direct interrelation with fever continued time and the ratio of unusual lymphocyte. There was a negative interrelation between CCR5 and fever continued time (P < 0.05). Children infectious of IM expressed higher level of CCR3 + and lower level of CCR5 + and there was a tendency of Th2 polarization with over production of T helper cell divide imbalance. CCR3 + and CCR5 + may be important targets to judge the degree of seriousness of IM.

  16. Tc-99m MAG3 SPECT on transplanted kidney

    International Nuclear Information System (INIS)

    Ryu, Jong Gul; Kim, Soon; Zeon, Seok Kil

    1999-01-01

    This study was designed to evaluate the usefulness of a technetium-99m mercaptoacetyltriglycine (Tc-99m MAG3) single photon emission computed tomography (SPECT) performed on transplanted kidney. Thirty renal transplant patients were included in this study. Planar scan was performed for 30 minutes using 555 MBq Tc-99m MAG3. A post-voiding SPECT scan was acquired on the third, seventh, fourteenth and twenty eighth day after transplantation. SPECT scan showed interpretable image quality in 26 of 30 patients (86.7%) and 84 in 120 scans (70%). Fourteen of 26 patients with interpretable SPECT image showed decreased or increased radioactivity, but only 5 had abnormal findings on the planar scan. Focal SPECT defects were seen in allografts with normal function (n=3), acute tubular necrosis (n=3), and acute rejection (n=2). The defects are thought to reflect focally underperfused renal parenchyme or, in normal allografts, an artifact from uneven radioactivity distribution. Four of 10 paints with renal arterial variation showed focally decreased radioactivity and SPECT helped guide further studies that confirmed the exact cause. Five of 10 patients with acute tubular necrosis or acute rejection showed focally decreased radioactivity, but its relation to the patients' clinical course was not clear. Focally increased radioactivity was observed in 5 allografts with normal function and 1 with double ureter in which local clearance delay was observed. Tc-99m MAG3 SPECT renal scan can detect additional focal abnormalities compared to planar scan. Further study is necessary to elucidate the exact clinical significance of the SPECT findings

  17. In-silico guided discovery of novel CCR9 antagonists

    Science.gov (United States)

    Zhang, Xin; Cross, Jason B.; Romero, Jan; Heifetz, Alexander; Humphries, Eric; Hall, Katie; Wu, Yuchuan; Stucka, Sabrina; Zhang, Jing; Chandonnet, Haoqun; Lippa, Blaise; Ryan, M. Dominic; Baber, J. Christian

    2018-03-01

    Antagonism of CCR9 is a promising mechanism for treatment of inflammatory bowel disease, including ulcerative colitis and Crohn's disease. There is limited experimental data on CCR9 and its ligands, complicating efforts to identify new small molecule antagonists. We present here results of a successful virtual screening and rational hit-to-lead campaign that led to the discovery and initial optimization of novel CCR9 antagonists. This work uses a novel data fusion strategy to integrate the output of multiple computational tools, such as 2D similarity search, shape similarity, pharmacophore searching, and molecular docking, as well as the identification and incorporation of privileged chemokine fragments. The application of various ranking strategies, which combined consensus and parallel selection methods to achieve a balance of enrichment and novelty, resulted in 198 virtual screening hits in total, with an overall hit rate of 18%. Several hits were developed into early leads through targeted synthesis and purchase of analogs.

  18. The chemokine receptor CCR2 maintains plasmacytoid dendritic cell homeostasis

    DEFF Research Database (Denmark)

    Cédile, Oriane; Østerby Jørgensen, Line; Frank, Ida

    2017-01-01

    Thymic dendritic cells (DC) play a role in central tolerance. Three thymic DC subtypes have been described: plasmacytoid DC (pDC) and two conventional DC (cDC), CD8α+ Sirpα- DC and Sirpα+ CD8α- cDC. Both pDC and Sirpα+ cDC can take up antigen in periphery and migrate into the thymus in response t...... by CCL2 or CCR2 deficiency. Although some thymic progenitors expressed CCR2, this did not include those that give rise to pDC. Based on these results, we propose that CCR2 is involved in pDC homeostasis but its ligand CCL2 does not play a major role....

  19. CCR Certification Form for Wyoming or EPA R8 Tribal Community Water Systems

    Science.gov (United States)

    The CCR Certification Form can be used to certify that community water systems in Wyoming or on Tribal Lands in EPA Region 8 have completed and distributed their annual Consumer Confidence Report (CCR) or water quality report.

  20. The discovery of tropane-derived CCR5 receptor antagonists.

    Science.gov (United States)

    Armour, Duncan R; de Groot, Marcel J; Price, David A; Stammen, Blanda L C; Wood, Anthony; Perros, Manos; Burt, Catherine

    2006-04-01

    The development of compound 1, a piperidine-based CCR5 receptor antagonist with Type I CYP2D6 inhibition, into the tropane-derived analogue 5, is described. This compound, which is devoid of CYP2D6 liabilities, is a highly potent ligand for the CCR5 receptor and has broad-spectrum activity against a range of clinically relevant HIV isolates. The identification of human ether a-go-go-related gene channel inhibition within this series is described and the potential for QTc interval prolongation discussed. Furthermore, structure activity relationship (SAR) around the piperidine moiety is also described.

  1. Molecular characterization and expression analysis of four fish-specific CC chemokine receptors CCR4La, CCR4Lc1, CCR4Lc2 and CCR11 in rainbow trout (Oncorhynchus mykiss).

    Science.gov (United States)

    Qi, Zhitao; Holland, Jason W; Jiang, Yousheng; Secombes, Christopher J; Nie, Pin; Wang, Tiehui

    2017-09-01

    The chemokine and chemokine receptor networks regulate leukocyte trafficking, inflammation, immune cell differentiation, cancer and other biological processes. Comparative immunological studies have revealed that both chemokines and their receptors have expanded greatly in a species/lineage specific way. Of the 10 human CC chemokine receptors (CCR1-10) that bind CC chemokines, orthologues only to CCR6, 7, 9 and 10 are present in teleost fish. In this study, four fish-specific CCRs, termed as CCR4La, CCR4Lc1, CCR4Lc2 and CCR11, with a close link to human CCR1-5 and 8, in terms of amino acid homology and syntenic conservation, have been identified and characterized in rainbow trout (Oncorhynchus mykiss). These CCRs were found to possess the conserved features of the G protein-linked receptor family, including an extracellular N-terminal, seven TM domains, three extracellular loops and three intracellular loops, and a cytoplasmic carboxyl tail with multiple potential serine/threonine phosphorylation sites. Four cysteine residues known to be involved in forming two disulfide bonds are present in the extracellular domains and a DRY motif is present in the second intracellular loop. Signaling mediated by these receptors might be regulated by N-glycosylation, tyrosine sulfation, S-palmitoylation, a PDZ ligand motif and di-leucine motifs. Studies of intron/exon structure revealed distinct fish-specific CCR gene organization in different fish species/lineages that might contribute to the diversification of the chemokine ligand-receptor networks in different fish lineages. Fish-specific trout CCRs are highly expressed in immune tissues/organs, such as thymus, spleen, head kidney and gills. Their expression can be induced by the pro-inflammatory cytokines, IL-1β, IL-6 and IFNγ, by the pathogen associated molecular patterns, PolyIC and peptidoglycan, and by bacterial infection. These data suggest that fish-specific CCRs are likely to have an important role in immune

  2. Solution Structure of LC4 Transmembrane Segment of CCR5

    OpenAIRE

    Miyamoto, Kazuhide; Togiya, Kayo

    2011-01-01

    CC-chemokine receptor 5 (CCR5) is a specific co-receptor allowing the entry of human immunodeficiency virus type 1 (HIV-1). The LC4 region in CCR5 is required for HIV-1 entry into the cells. In this study, the solution structure of LC4 in SDS micelles was elucidated by using standard 1H two-dimensional NMR spectroscopy, circular dichroism, and fluorescdence quenching. The LC4 structure adopts two helical structures, whereas the C-terminal part remains unstructured. The positions in which LC4 ...

  3. Tumor hypoxia modulates podoplanin/CCL21 interactions in CCR7+ NK cell recruitment and CCR7+ tumor cell mobilization.

    Science.gov (United States)

    Tejchman, Anna; Lamerant-Fayel, Nathalie; Jacquinet, Jean-Claude; Bielawska-Pohl, Aleksandra; Mleczko-Sanecka, Katarzyna; Grillon, Catherine; Chouaib, Salem; Ugorski, Maciej; Kieda, Claudine

    2017-05-09

    Podoplanin (PDPN), an O-glycosylated, transmembrane, mucin-type glycoprotein, is expressed by cancer associated fibroblasts (CAFs). In malignant transformation, PDPN is subjected to changes and its role is yet to be established. Here we show that it is involved in modulating the activity of the CCL21/CCR7 chemokine/receptor axis in a hypoxia-dependent manner. In the present model, breast cancer MDA-MB-231 cells and NKL3 cells express the surface CCR7 receptor for CCL21 chemokine which is a potent chemoattractant able to bind to PDPN. The impact of the CCL21/CCR7 axis in the molecular mechanism of the adhesion of NKL3 cells and of MDA-MB-231 breast cancer cells was reduced in a hypoxic tumor environment. In addition to its known effect on migration, CCL21/CCR7 interaction was shown to allow NK cell adhesion to endothelial cells (ECs) and its reduction by hypoxia. A PDPN expressing model of CAFs made it possible to demonstrate the same CCL21/CCR7 axis involvement in the tumor cells to CAFs recognition mechanism through PDPN binding of CCL21. PDPN was induced by hypoxia and its overexpression undergoes a reduction of adhesion, making it an anti-adhesion molecule in the absence of CCL21, in the tumor. CCL21/CCR7 modulated NK cells/ECs and MDA-MB-231 cells/CAF PDPN-dependent interactions were further shown to be linked to hypoxia-dependent microRNAs as miRs: miR-210 and specifically miR-21, miR-29b which influence PDPN expression.

  4. 77 FR 5471 - Announcement of Public Meeting on the Consumer Confidence Report (CCR) Rule Retrospective Review

    Science.gov (United States)

    2012-02-03

    ... Announcement of Public Meeting on the Consumer Confidence Report (CCR) Rule Retrospective Review AGENCY... stakeholder input on the Consumer Confidence Report (CCR) Rule as part of the agency's Retrospective Review of... Safe Drinking Water Act (SDWA, section 1414(c)). The Consumer Confidence Report, or CCR, is an annual...

  5. Molecular requirements for inhibition of the chemokine receptor CCR8--probe-dependent allosteric interactions

    DEFF Research Database (Denmark)

    Rummel, Pia Cwarzko; Arfelt, K N; Baumann, L

    2012-01-01

    Here we present a novel series of CCR8 antagonists based on a naphthalene-sulfonamide structure. This structure differs from the predominant pharmacophore for most small-molecule CC-chemokine receptor antagonists, which in fact activate CCR8, suggesting that CCR8 inhibition requires alternative...

  6. Discovery and mapping of an intracellular antagonist binding site at the chemokine receptor CCR2

    DEFF Research Database (Denmark)

    Zweemer, Annelien J M; Bunnik, Julia; Veenhuizen, Margo

    2014-01-01

    be divided into two groups with most likely two topographically distinct binding sites. The aim of the current study was to identify the binding site of one such group of ligands, exemplified by three allosteric antagonists, CCR2-RA-[R], JNJ-27141491, and SD-24. We first used a chimeric CCR2/CCR5 receptor...

  7. Benzimidazoles as benzamide replacements within cyclohexane-based CC chemokine receptor 2 (CCR2) antagonists.

    Science.gov (United States)

    Cherney, Robert J; Mo, Ruowei; Meyer, Dayton T; Pechulis, Anthony D; Guaciaro, Michael A; Lo, Yvonne C; Yang, Gengjie; Miller, Persymphonie B; Scherle, Peggy A; Zhao, Qihong; Cvijic, Mary Ellen; Barrish, Joel C; Decicco, Carl P; Carter, Percy H

    2012-10-01

    We describe the design, synthesis, and evaluation of benzimidazoles as benzamide replacements within a series of trisubstituted cyclohexane CCR2 antagonists. 7-Trifluoromethylbenzimidazoles displayed potent binding and functional antagonism of CCR2 while being selective over CCR3. These benzimidazoles were also incorporated into lactam-containing antagonists, thus completely eliminating the customary bis-amide. Copyright © 2012 Elsevier Ltd. All rights reserved.

  8. Assessment of renal function with the Tc-99m-MAG3 clearance

    International Nuclear Information System (INIS)

    Keske, U.; Corcles, M.; Andreessen, R.; Wilfling, M.; Roll, D.; Gahl, G.; Felix, R.

    1990-01-01

    This paper evaluates the applicability of the 99m-Tc-mercaptoacetyle-triglycine (MAG3) clearance for the documentation of renal function. Renal clearance was measured with the method of Tauxe in 699 patients during routine renal scintigraphy with 80 MBq of 99mTc-MAG3. Serum creatinine level and MAG3 clearance show an inverse correlation. Patients with an elevated serum creatinine level constantly have a lowered MAG3 clearance and vice versa. For creatinine values lower than 1.8 mg/dL, minor changes in creatinine level are accompanied by large changes in MAG3 clearance. Age (in years) dependence of MAG3 clearance was evaluated in 487 patients who showed no evidence of impaired renal function

  9. "Lights on at the end of the party": are lads' mags mainstreaming dangerous sexism?

    Science.gov (United States)

    Horvath, Miranda A H; Hegarty, Peter; Tyler, Suzannah; Mansfield, Sophie

    2012-11-01

    Research has suggested that some magazines targeted at young men - lads' mags - are normalizing extreme sexist views by presenting those views in a mainstream context. Consistent with this view, young men in Study 1 (n = 90) identified more with derogatory quotes about women drawn from recent lads' mags, and from interviews with convicted rapists, when those quotes were attributed to lads' mags, than when they were attributed to convicted rapists. In Study 2, 40 young women and men could not reliably judge the source of those same quotes. While these participants sometimes voiced the belief that the content of lads' mags was 'normal' while rapists' talk was 'extreme', they categorized quotes from both sources as derogatory with equal frequency. Jointly, the two studies show an overlap in the content of convicted rapists' talk and the contents of contemporary lads' mags, and suggest that the framing of such content within lads' mags may normalize it for young men. ©2011 The British Psychological Society.

  10. Central extensions for the Weyl CCR in Curved space

    International Nuclear Information System (INIS)

    Emch, G.G.

    1993-01-01

    For non-necessarily flat homogeneous configuration spaces, we illustrate how the cohomological choices made in the definition a Weyl group of the CCR are reflected in the momentum map for the action of this group on its co-adjoint orbit of maximal dimension. (Author) 8 refs

  11. Aplicabilidad del monitoreo de emisiones del arco eléctrico para el control de calidad en el proceso MAG-S Applicability of monitoring of electric arc emissions for quality control in MAG-S process

    Directory of Open Access Journals (Sweden)

    Eber Huanca Cayo

    2011-12-01

    Full Text Available Garantizar la calidad en soldadura no es una tarea trivial. Para ello diversas inspecciones de control de calidad son realizadas, en detrimento, los costos y tiempos de producción se elevan. Existen diversos sistemas automatizados de soldadura, éstos son auxiliados por sistemas de control basados en el monitoreo de parámetros de soldadura. Sin embargo son reducidos los sistemas automatizados de monitoreo de calidad que en su mayoría son diseñados para el proceso TIG. Durante la soldadura, el arco eléctrico produce emisiones acústicas y electromagnéticas que se manifiestan como sonido y luminosidad. El objetivo del presente trabajo es mostrar que estas emisiones del arco pueden ser utilizados para el monitoreo de la calidad de la soldadura para el proceso MAG-S. Se realizaron múltiples experimentos de soldadura en posición plana donde se indujeron perturbaciones consistentes presencia de grasa y ausencia de gas de protección. En cada experimento se adquirió simultáneamente señales de tensión y corriente así como señales de emisiones del arco eléctrico. A partir de las emisiones acústicas y electromagnéticas en la banda de ultravioleta, se midió la frecuencia de cortocircuitos. A partir de la emisión electromagnética en la banda infrarroja se midió la estabilidad del proceso de soldadura. Los resultados muestran que las emisiones del arco pueden ser utilizadas para el monitoreo y detección de perturbaciones en soldadura y con el entendimiento de las variaciones de cada emisión podría identificarse determinados tipos de perturbaciones.Ensuring quality in welding is not a trivial task. For this purpose several quality control checks are performed, at the expense, costs and production times are increased. There are several automated welding systems and they are assisted by control systems based on monitoring of welding parameters. However, automated quality monitoring systems are limited and they are mostly designed for the

  12. Effects of CCR5-delta32 and CCR2-64I alleles on disease progression of perinatally HIV-1-infected children: an international meta-analysis.

    Science.gov (United States)

    Ioannidis, John P A; Contopoulos-Ioannidis, Despina G; Rosenberg, Philip S; Goedert, James J; De Rossi, Anita; Espanol, Teresa; Frenkel, Lisa; Mayaux, Marie-Jeanne; Newell, Marie-Louise; Pahwa, Savita G; Rousseau, Christine; Scarlatti, Gabriella; Sei, Shizuko; Sen, Luisa; O'Brien, Thomas R

    2003-07-25

    Among perinatally infected children, the effects of certain alleles of the CCR5 and CCR2 genes on the rate of disease progression remain unclear. We addressed the effects of CCR5-delta32 and CCR2-64I in an international meta-analysis. Genotype data were contributed from 10 studies with 1317 HIV-1-infected children (7263 person-years of follow-up). Time-to-event analyses were performed stratified by study and racial group. Endpoints included progression to clinical AIDS, death, and death after the diagnosis of clinical AIDS. The time-dependence of the genetic effects was specifically investigated. There was large heterogeneity in the observed rates of disease progression between different cohorts. For progression to clinical AIDS, both CCR5-delta32 and CCR2-64I showed overall non-significant trends for protection [hazard ratios 0.84, 95% confidence interval (CI) 0.58-1.23; and 0.87, 95% CI 0.67-1.14, respectively]. However, analyses of survival showed statistically significant time-dependence. No deaths occurred among CCR5-delta32 carriers in the first 3 years of life, whereas there was no protective effect (hazard ratio 0.95; 95% CI 0.43-2.10) in later years (P=0.01 for the time-dependent model). For CCR2-64I, the hazard ratio for death was 0.69 (95% CI 0.39-1.21) in the first 6 years of life and 2.56 (95% CI 1.26-5.20) in subsequent years (P<0.01 for the time-dependent model). CCR5-delta32 and CCR2-64I offered no clear protection after clinical AIDS had developed. The CCR5-delta32 and CCR2-64I alleles are associated with a decreased risk of death among perinatally infected children, but only for the first years of life.

  13. CCR5 and CXCR3 are dispensable for liver infiltration, but CCR5 protects against virus-induced T-cell-mediated hepatic steatosis

    DEFF Research Database (Denmark)

    Holst, P J; Orskov, C; Qvortrup, K

    2007-01-01

    CCR5 and CXCR3 are important molecules in regulating the migration of activated lymphocytes. Thus, the majority of tissue-infiltrating T cells found in the context of autoimmune conditions and viral infections express CCR5 and CXCR3, and the principal chemokine ligands are expressed within inflam...... of CCR5 is associated with the induction of CD8(+) T-cell-mediated immunopathology consisting of marked hepatic microvesicular steatosis....

  14. Adverse effect of the CCR5 promoter -2459A allele on HIV-1 disease progression

    DEFF Research Database (Denmark)

    Knudsen, T B; Kristiansen, T B; Katzenstein, T L

    2001-01-01

    /G transition that has been discovered recently, have also been shown to influence HIV progression. Since genetic linkages make these polymorphisms interdependent variables, the aim of the present study was to isolate and evaluate the effect on HIV disease progression for each of these mutations independently......HIV positive individuals heterozygous for a 32 basepair deletion in the CCR5 encoding gene (CCR5 Delta32) have a reduced number of CCR5 receptors on the cell surface and a slower progression towards AIDS and death. Other human polymorphisms, such as the CCR2 64I and the CCR5 promoter -2459 A...

  15. An anti-CCR5 monoclonal antibody and small molecule CCR5 antagonists synergize by inhibiting different stages of human immunodeficiency virus type 1 entry

    International Nuclear Information System (INIS)

    Safarian, Diana; Carnec, Xavier; Tsamis, Fotini; Kajumo, Francis; Dragic, Tatjana

    2006-01-01

    HIV-1 coreceptors are attractive targets for novel antivirals. Here, inhibition of entry by two classes of CCR5 antagonists was investigated. We confirmed previous findings that HIV-1 isolates vary greatly in their sensitivity to small molecule inhibitors of CCR5-mediated entry, SCH-C and TAK-779. In contrast, an anti-CCR5 monoclonal antibody (PA14) similarly inhibited entry of diverse viral isolates. Sensitivity to small molecules was V3 loop-dependent and inversely proportional to the level of gp120 binding to CCR5. Moreover, combinations of the MAb and small molecules were highly synergistic in blocking HIV-1 entry, suggesting different mechanisms of action. This was confirmed by time course of inhibition experiments wherein the PA14 MAb and small molecules were shown to inhibit temporally distinct stages of CCR5 usage. We propose that small molecules inhibit V3 binding to the second extracellular loop of CCR5, whereas PA14 preferentially inhibits subsequent events such as CCR5 recruitment into the fusion complex or conformational changes in the gp120-CCR5 complex that trigger fusion. Importantly, our findings suggest that combinations of CCR5 inhibitors with different mechanisms of action will be central to controlling HIV-1 infection and slowing the emergence of resistant strains

  16. Network interactions: non-geniculate input to V1.

    Science.gov (United States)

    Muckli, Lars; Petro, Lucy S

    2013-04-01

    The strongest connections to V1 are fed back from neighbouring area V2 and from a network of higher cortical areas (e.g. V3, V5, LOC, IPS and A1), transmitting the results of cognitive operations such as prediction, attention and imagination. V1 is therefore at the receiving end of a complex cortical processing cascade and not only at the entrance stage of cortical processing of retinal input. One elegant strategy to investigate this information-rich feedback to V1 is to eliminate feedforward input, that is, exploit V1's retinotopic organisation to isolate subregions receiving no direct bottom-up stimulation. We highlight the diverse mechanisms of cortical feedback, ranging from gain control to predictive coding, and conclude that V1 is involved in rich internal communication processes. Copyright © 2013 Elsevier Ltd. All rights reserved.

  17. Analysis of substrate specificity of Schizosaccharomyces pombe Mag1 alkylpurine DNA glycosylase

    Energy Technology Data Exchange (ETDEWEB)

    Adhikary, Suraj; Eichman, Brandt F. (Vanderbilt)

    2014-10-02

    DNA glycosylases specialized for the repair of alkylation damage must identify, with fine specificity, a diverse array of subtle modifications within DNA. The current mechanism involves damage sensing through interrogation of the DNA duplex, followed by more specific recognition of the target base inside the active site pocket. To better understand the physical basis for alkylpurine detection, we determined the crystal structure of Schizosaccharomyces pombe Mag1 (spMag1) in complex with DNA and performed a mutational analysis of spMag1 and the close homologue from Saccharomyces cerevisiae (scMag). Despite strong homology, spMag1 and scMag differ in substrate specificity and cellular alkylation sensitivity, although the enzymological basis for their functional differences is unknown. We show that Mag preference for 1,N{sup 6}-ethenoadenine ({var_epsilon}A) is influenced by a minor groove-interrogating residue more than the composition of the nucleobase-binding pocket. Exchanging this residue between Mag proteins swapped their {var_epsilon}A activities, providing evidence that residues outside the extrahelical base-binding pocket have a role in identification of a particular modification in addition to sensing damage.

  18. Neurophysiological and clinical responses to rituximab in patients with anti-MAG polyneuropathy.

    Science.gov (United States)

    Zara, Gabriella; Zambello, Renato; Ermani, M

    2011-12-01

    Rituximab treatment has shown clinical improvement in anti-myelin associated glycoprotein (MAG) polyneuropathy. We analyzed scores of clinical scales and the most sensitive electrophysiological parameters before and after immunomodulating treatment with rituximab in a group of patients affected by anti-MAG demyelinating polyneuropathy. Clinical scores, the percentage of CD20 B-lymphocytes, anti-MAG antibody titers and electrophysiological data in 7 patients with anti-MAG polyneuropathy were analyzed. The patients were examined before a cycle with rituximab, 6, 12 and 24 months after the end of the treatment. Two patients were treated with rituximab additional cycles and re-evaluated 48 months after the first treatment. There were no evident correlation between anti-MAG serum antibody titers or clinical scales and electrodiagnostic data. Significant decrease in the proportion of CD20 B-lymphocytes was observed. Significant anti-MAG antibodies titers reduction was detected after re-treatment. At follow-up, pinprik sensation and two point discrimination presented a significant improvement compared with the score before treatment. In our patients, rituximab did not improve any electrophysiological data. No correlation with anti-MAG serum antibodies course was found. With rituximab only pin sensibility improved. Rituximab re-treatment significantly reduces anti-MAG serum antibodies titers but improves only small fibers sensibility. Copyright © 2011 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

  19. 75 FR 76962 - Application To Export Electric Energy; MAG Energy Solutions, Inc.

    Science.gov (United States)

    2010-12-10

    ... DEPARTMENT OF ENERGY [OE Docket No. EA-306-A] Application To Export Electric Energy; MAG Energy... electric energy from the United States to Canada pursuant to section 202(e) of the Federal Power Act (FPA... of Energy (DOE) issued Order No. EA-306, which authorized MAG E.S. to transmit electric energy from...

  20. Genetic Polymorphism at CCL5 Is Associated With Protection in Chagas’ Heart Disease: Antagonistic Participation of CCR1+ and CCR5+ Cells in Chronic Chagasic Cardiomyopathy

    Directory of Open Access Journals (Sweden)

    Angelica Martins Batista

    2018-04-01

    Full Text Available Chronic cardiomyopathy is the main clinical manifestation of Chagas disease (CD, a disease caused by Trypanosoma cruzi infection. A hallmark of chronic chagasic cardiomyopathy (CCC is a fibrogenic inflammation mainly composed of CD8+ and CD4+ T cells and macrophages. CC-chemokine ligands and receptors have been proposed to drive cell migration toward the heart tissue of CD patients. Single nucleotide polymorphisms (SNPs in CC-chemokine ligand and receptor genes may determine protein expression. Herein, we evaluated the association of SNPs in the CC-chemokines CCL2 (rs1024611 and CCL5 (rs2107538, rs2280788 and the CCL5/RANTES receptors CCR1 (rs3181077, rs1491961, rs3136672 and CCR5 (rs1799987 with risk and progression toward CCC. We performed a cross-sectional association study of 406 seropositive patients from endemic areas for CD in the State of Pernambuco, Northeast Brazil. The patients were classified as non-cardiopathic (A, n = 110 or cardiopathic (mild, B1, n = 163; severe, C, n = 133. Serum levels of CCL5 and CCL2/MCP-1 were elevated in CD patients but were neither associated with risk/severity of CCC nor with SNP genotypes. After logistic regression analysis with adjustment for the covariates gender and ethnicity, CCL5 −403 (rs2107538 CT heterozygotes (OR = 0.5, P-value = 0.04 and T carriers (OR = 0.5, P-value = 0.01 were associated with protection against CCC. To gain insight into the participation of the CCL5–CCR5/CCR1 axis in CCC, mice were infected with the Colombian T. cruzi strain. Increased CCL5 concentrations were detected in cardiac tissue. In spleen, frequencies of CCR1+ CD8+ T cells and CD14+ macrophages were decreased, while frequencies of CCR5+ cells were increased. Importantly, CCR1+CD14+ macrophages were mainly IL-10+, while CCR5+ cells were mostly TNF+. CCR5-deficient infected mice presented reduced TNF concentrations and injury in heart tissue. Selective blockade of CCR1 (Met-RANTES therapy

  1. Genetic Polymorphism at CCL5 Is Associated With Protection in Chagas' Heart Disease: Antagonistic Participation of CCR1+ and CCR5+ Cells in Chronic Chagasic Cardiomyopathy.

    Science.gov (United States)

    Batista, Angelica Martins; Alvarado-Arnez, Lucia Elena; Alves, Silvia Marinho; Melo, Gloria; Pereira, Isabela Resende; Ruivo, Leonardo Alexandre de Souza; da Silva, Andrea Alice; Gibaldi, Daniel; da Silva, Thayse do E S Protásio; de Lorena, Virginia Maria Barros; de Melo, Adriene Siqueira; de Araújo Soares, Ana Karine; Barros, Michelle da Silva; Costa, Vláudia Maria Assis; Cardoso, Cynthia C; Pacheco, Antonio G; Carrazzone, Cristina; Oliveira, Wilson; Moraes, Milton Ozório; Lannes-Vieira, Joseli

    2018-01-01

    Chronic cardiomyopathy is the main clinical manifestation of Chagas disease (CD), a disease caused by Trypanosoma cruzi infection. A hallmark of chronic chagasic cardiomyopathy (CCC) is a fibrogenic inflammation mainly composed of CD8 + and CD4 + T cells and macrophages. CC-chemokine ligands and receptors have been proposed to drive cell migration toward the heart tissue of CD patients. Single nucleotide polymorphisms (SNPs) in CC-chemokine ligand and receptor genes may determine protein expression. Herein, we evaluated the association of SNPs in the CC-chemokines CCL2 (rs1024611) and CCL5 (rs2107538, rs2280788) and the CCL5/RANTES receptors CCR1 (rs3181077, rs1491961, rs3136672) and CCR5 (rs1799987) with risk and progression toward CCC. We performed a cross-sectional association study of 406 seropositive patients from endemic areas for CD in the State of Pernambuco, Northeast Brazil. The patients were classified as non-cardiopathic (A, n  = 110) or cardiopathic (mild, B1, n  = 163; severe, C, n  = 133). Serum levels of CCL5 and CCL2/MCP-1 were elevated in CD patients but were neither associated with risk/severity of CCC nor with SNP genotypes. After logistic regression analysis with adjustment for the covariates gender and ethnicity, CCL5 -403 (rs2107538) CT heterozygotes (OR = 0.5, P -value = 0.04) and T carriers (OR = 0.5, P -value = 0.01) were associated with protection against CCC. To gain insight into the participation of the CCL5-CCR5/CCR1 axis in CCC, mice were infected with the Colombian T. cruzi strain. Increased CCL5 concentrations were detected in cardiac tissue. In spleen, frequencies of CCR1 + CD8 + T cells and CD14 + macrophages were decreased, while frequencies of CCR5 + cells were increased. Importantly, CCR1 + CD14 + macrophages were mainly IL-10 + , while CCR5 + cells were mostly TNF + . CCR5-deficient infected mice presented reduced TNF concentrations and injury in heart tissue. Selective blockade of CCR1 (Met

  2. Genetic Polymorphism at CCL5 Is Associated With Protection in Chagas’ Heart Disease: Antagonistic Participation of CCR1+ and CCR5+ Cells in Chronic Chagasic Cardiomyopathy

    Science.gov (United States)

    Batista, Angelica Martins; Alvarado-Arnez, Lucia Elena; Alves, Silvia Marinho; Melo, Gloria; Pereira, Isabela Resende; Ruivo, Leonardo Alexandre de Souza; da Silva, Andrea Alice; Gibaldi, Daniel; da Silva, Thayse do E. S. Protásio; de Lorena, Virginia Maria Barros; de Melo, Adriene Siqueira; de Araújo Soares, Ana Karine; Barros, Michelle da Silva; Costa, Vláudia Maria Assis; Cardoso, Cynthia C.; Pacheco, Antonio G.; Carrazzone, Cristina; Oliveira, Wilson; Moraes, Milton Ozório; Lannes-Vieira, Joseli

    2018-01-01

    Chronic cardiomyopathy is the main clinical manifestation of Chagas disease (CD), a disease caused by Trypanosoma cruzi infection. A hallmark of chronic chagasic cardiomyopathy (CCC) is a fibrogenic inflammation mainly composed of CD8+ and CD4+ T cells and macrophages. CC-chemokine ligands and receptors have been proposed to drive cell migration toward the heart tissue of CD patients. Single nucleotide polymorphisms (SNPs) in CC-chemokine ligand and receptor genes may determine protein expression. Herein, we evaluated the association of SNPs in the CC-chemokines CCL2 (rs1024611) and CCL5 (rs2107538, rs2280788) and the CCL5/RANTES receptors CCR1 (rs3181077, rs1491961, rs3136672) and CCR5 (rs1799987) with risk and progression toward CCC. We performed a cross-sectional association study of 406 seropositive patients from endemic areas for CD in the State of Pernambuco, Northeast Brazil. The patients were classified as non-cardiopathic (A, n = 110) or cardiopathic (mild, B1, n = 163; severe, C, n = 133). Serum levels of CCL5 and CCL2/MCP-1 were elevated in CD patients but were neither associated with risk/severity of CCC nor with SNP genotypes. After logistic regression analysis with adjustment for the covariates gender and ethnicity, CCL5 −403 (rs2107538) CT heterozygotes (OR = 0.5, P-value = 0.04) and T carriers (OR = 0.5, P-value = 0.01) were associated with protection against CCC. To gain insight into the participation of the CCL5–CCR5/CCR1 axis in CCC, mice were infected with the Colombian T. cruzi strain. Increased CCL5 concentrations were detected in cardiac tissue. In spleen, frequencies of CCR1+ CD8+ T cells and CD14+ macrophages were decreased, while frequencies of CCR5+ cells were increased. Importantly, CCR1+CD14+ macrophages were mainly IL-10+, while CCR5+ cells were mostly TNF+. CCR5-deficient infected mice presented reduced TNF concentrations and injury in heart tissue. Selective blockade of CCR1 (Met-RANTES therapy) in

  3. Role of CCL-2, CCR-2 and CCR-4 in cerulein-induced acute pancreatitis and pancreatitis-associated lung injury.

    Science.gov (United States)

    Frossard, Jean Louis; Lenglet, Sébastien; Montecucco, Fabrizio; Steffens, Sabine; Galan, Katia; Pelli, Graziano; Spahr, Laurent; Mach, Francois; Hadengue, Antoine

    2011-05-01

    Acute pancreatitis is an inflammatory process of variable severity. Leucocytes are thought to play a key role in the development of pancreatitis and pancreatitis-associated lung injury. The interactions between inflammatory cells and their mediators are crucial for determining tissue damage. Monocyte chemoattractant protein-1 (or CCL-2), CCR-2 and CCR-4 are chemokines and chemokine receptors involved in leucocyte trafficking. The aim of the study was to evaluate the role of the CCL-2, CCR-2 and CCR-4 chemokine receptors in the pathogenesis of cerulein-induced pancreatitis and pancreatitis-associated lung injury. To address the role of CCL-2, CCR-2 and CCR-4 that attracts leucocytes cells in inflamed tissues, pancreatitis was induced by administering supramaximal doses of cerulein in mice that do not express CCL-2, CCR-2 or CCR-4. The severity of pancreatitis was measured by serum amylase, pancreatic oedema and acinar cell necrosis. Lung injury was quantitated by evaluating lung microvascular permeability and lung myeloperoxidase activity. Chemokine and chemokine-receptor expression were quantitated by real-time PCR. The nature of inflammatory cells invading the pancreas and lungs was studied by immunostaining. The authors have found that pancreas CCL-2 and CCR-2 levels rise during pancreatitis. Both pancreatitis and the associated lung injury are blunted, but not completely prevented, in mice deficient in CCL-2, whereas the deficiency in either CCR-2 or CCR-4 does not reduce the severity of both the pancreatitis and the lung injury. The amounts of neutrophils and monocyte/macrophages (MOMA)-2 cells were significantly lower in mice deficient in CCL-2 compared with their sufficient littermates. These results suggest that CCL-2 plays a key role in pancreatitis by modulating the infiltration by neutrophils and MOMA-2 cells, and that its deficiency may improve the outcome of the disease.

  4. Solar Probe Plus MAG Sensor Thermal Design for Low Heater Power and Extreme Thermal Environment

    Science.gov (United States)

    Choi, Michael K.

    2015-01-01

    The heater power available for the Solar Probe Plus FIELDS MAG sensor is less than half of the heritage value for other missions. Nominally the MAG sensors are in the spacecraft's umbra. In the worst hot case, approximately 200 spacecraft communication downlinks, up to 10 hours each, are required at 0.7 AU. These downlinks require the spacecraft to slew 45 deg. about the Y-axis, exposing the MAG sensors and boom to sunlight. This paper presents the thermal design to meet the MAG sensor thermal requirements in the extreme thermal environment and with low heater power. A thermal balance test on the MAG sensor engineering model has verified the thermal design and correlated the thermal model for flight temperature predictions.

  5. BinMag: Widget for comparing stellar observed with theoretical spectra

    Science.gov (United States)

    Kochukhov, O.

    2018-05-01

    BinMag examines theoretical stellar spectra computed with Synth/SynthMag/Synmast/Synth3/SME spectrum synthesis codes and compare them to observations. An IDL widget program, BinMag applies radial velocity shift and broadening to the theoretical spectra to account for the effects of stellar rotation, radial-tangential macroturbulence, instrumental smearing. The code can also simulate spectra of spectroscopic binary stars by appropriate coaddition of two synthetic spectra. Additionally, BinMag can be used to measure equivalent width, fit line profile shapes with analytical functions, and to automatically determine radial velocity and broadening parameters. BinMag interfaces with the Synth3 (ascl:1212.010) and SME (ascl:1202.013) codes, allowing the user to determine chemical abundances and stellar atmospheric parameters from the observed spectra.

  6. Glomerular filtration and tubular secretion of MAG-3 in the rat kidney

    International Nuclear Information System (INIS)

    Mueller-Suur, R.M.; Mueller-Suur, C.

    1989-01-01

    Technetium-99m mercaptoacetyltriglycine (MAG-3) has recently been introduced as a new radiopharmaceutical for dynamic renal scintigraphy. To elucidate the mechanism of renal excretion, micropuncture experiments were performed in rat kidneys for direct measurements of glomerular filtration and tubular secretory capacity. Fluid of Bowman space was collected from superficial glomeruli and analyzed for its contents of [99mTc]MAG-3, [125I]hippurate and [3H]inulin during constant infusion of these compounds. The ratio of activity of ultrafiltrate to that of arterial plasma was 0.23 for MAG-3, 0.68 for hippurate and 1.04 for inulin which demonstrates that the filtrated amount of MAG-3 is only 23% of that of inulin, presumably because of higher plasma protein binding which was also measured in vitro and found to be 80 +/- 1.5% for MAG-3 and 32 +/- 2% for [125I]hippurate. Proximal and distal tubules were also micropunctured and their tubular fluid as well as the final urine analyzed for the activity of hippurate and MAG-3. The tubular fluid to plasma ratio values along the nephron and in the final urine were all lower for MAG-3 than for hippurate, indicating a lower secretory capacity. From measurements of whole renal clearance, GFR and plasma protein binding the filtered amount of MAG-3 was 0.26 and of hippurate 0.87 ml/min.g kidney weight (p less than 0.001) and the secreted amount 2.01 and 2.38 ml/min.g kidney weight (p less than 0.05), respectively. We conclude that MAG-3 is predominantly excreted by tubular secretion and that the lower renal clearance of MAG-3 as compared with that of hippurate is a result both of a substantially decreased glomerular filtration and of a lower tubular secretion

  7. Metamorphosis of NPP A1, V1, V2

    International Nuclear Information System (INIS)

    Dobak, D.; Moncekova, M.

    2005-01-01

    In this book the history of construction, commissioning and exploitation of NPP A1, NPP V1 and NPP V2 in Jaslovske Bohunice is presented on documentary photos. Vicinity around of these NPPs is presented, too

  8. Regridded Harmonized World Soil Database v1.2

    Data.gov (United States)

    National Aeronautics and Space Administration — This data set describes select global soil parameters from the Harmonized World Soil Database (HWSD) v1.2, including additional calculated parameters such as area...

  9. Suppression of CCR impacts metabolite profile and cell wall composition in Pinus radiata tracheary elements.

    Science.gov (United States)

    Wagner, Armin; Tobimatsu, Yuki; Goeminne, Geert; Phillips, Lorelle; Flint, Heather; Steward, Diane; Torr, Kirk; Donaldson, Lloyd; Boerjan, Wout; Ralph, John

    2013-01-01

    Suppression of the lignin-related gene cinnamoyl-CoA reductase (CCR) in the Pinus radiata tracheary element (TE) system impacted both the metabolite profile and the cell wall matrix in CCR-RNAi lines. UPLC-MS/MS-based metabolite profiling identified elevated levels of p-coumaroyl hexose, caffeic acid hexoside and ferulic acid hexoside in CCR-RNAi lines, indicating a redirection of metabolite flow within phenylpropanoid metabolism. Dilignols derived from coniferyl alcohol such as G(8-5)G, G(8-O-4)G and isodihydrodehydrodiconiferyl alcohol (IDDDC) were substantially depleted, providing evidence for CCR's involvement in coniferyl alcohol biosynthesis. Severe CCR suppression almost halved lignin content in TEs based on a depletion of both H-type and G-type lignin, providing evidence for CCR's involvement in the biosynthesis of both lignin types. 2D-NMR studies revealed minor changes in the H:G-ratio and consequently a largely unchanged interunit linkage distribution in the lignin polymer. However, unusual cell wall components including ferulate and unsaturated fatty acids were identified in TEs by thioacidolysis, pyrolysis-GC/MS and/or 2D-NMR in CCR-RNAi lines, providing new insights into the consequences of CCR suppression in pine. Interestingly, CCR suppression substantially promoted pyrolytic breakdown of cell wall polysaccharides, a phenotype most likely caused by the incorporation of acidic compounds into the cell wall matrix in CCR-RNAi lines.

  10. Solution structure of LC4 transmembrane segment of CCR5.

    Directory of Open Access Journals (Sweden)

    Kazuhide Miyamoto

    Full Text Available CC-chemokine receptor 5 (CCR5 is a specific co-receptor allowing the entry of human immunodeficiency virus type 1 (HIV-1. The LC4 region in CCR5 is required for HIV-1 entry into the cells. In this study, the solution structure of LC4 in SDS micelles was elucidated by using standard 1H two-dimensional NMR spectroscopy, circular dichroism, and fluorescence quenching. The LC4 structure adopts two helical structures, whereas the C-terminal part remains unstructured. The positions in which LC4 binds to the HIV-1 inhibitory peptide LC5 were determined by docking calculations in addition to NMR data. The poses showed the importance of the hydrophobic interface of the assembled structures. The solution structure of LC4 elucidated in the present work provides a structural basis for further studies on the HIV-1 inhibitory function of the LC4 region.

  11. Solution structure of LC4 transmembrane segment of CCR5.

    Science.gov (United States)

    Miyamoto, Kazuhide; Togiya, Kayo

    2011-01-01

    CC-chemokine receptor 5 (CCR5) is a specific co-receptor allowing the entry of human immunodeficiency virus type 1 (HIV-1). The LC4 region in CCR5 is required for HIV-1 entry into the cells. In this study, the solution structure of LC4 in SDS micelles was elucidated by using standard 1H two-dimensional NMR spectroscopy, circular dichroism, and fluorescence quenching. The LC4 structure adopts two helical structures, whereas the C-terminal part remains unstructured. The positions in which LC4 binds to the HIV-1 inhibitory peptide LC5 were determined by docking calculations in addition to NMR data. The poses showed the importance of the hydrophobic interface of the assembled structures. The solution structure of LC4 elucidated in the present work provides a structural basis for further studies on the HIV-1 inhibitory function of the LC4 region.

  12. MAG4 versus alternative techniques for forecasting active region flare productivity

    Science.gov (United States)

    Falconer, David A; Moore, Ronald L; Barghouty, Abdulnasser F; Khazanov, Igor

    2014-01-01

    MAG4 is a technique of forecasting an active region's rate of production of major flares in the coming few days from a free magnetic energy proxy. We present a statistical method of measuring the difference in performance between MAG4 and comparable alternative techniques that forecast an active region's major-flare productivity from alternative observed aspects of the active region. We demonstrate the method by measuring the difference in performance between the “Present MAG4” technique and each of three alternative techniques, called “McIntosh Active-Region Class,” “Total Magnetic Flux,” and “Next MAG4.” We do this by using (1) the MAG4 database of magnetograms and major flare histories of sunspot active regions, (2) the NOAA table of the major-flare productivity of each of 60 McIntosh active-region classes of sunspot active regions, and (3) five technique performance metrics (Heidke Skill Score, True Skill Score, Percent Correct, Probability of Detection, and False Alarm Rate) evaluated from 2000 random two-by-two contingency tables obtained from the databases. We find that (1) Present MAG4 far outperforms both McIntosh Active-Region Class and Total Magnetic Flux, (2) Next MAG4 significantly outperforms Present MAG4, (3) the performance of Next MAG4 is insensitive to the forward and backward temporal windows used, in the range of one to a few days, and (4) forecasting from the free-energy proxy in combination with either any broad category of McIntosh active-region classes or any Mount Wilson active-region class gives no significant performance improvement over forecasting from the free-energy proxy alone (Present MAG4). Key Points Quantitative comparison of performance of pairs of forecasting techniques Next MAG4 forecasts major flares more accurately than Present MAG4 Present MAG4 forecast outperforms McIntosh AR Class and total magnetic flux PMID:26213517

  13. Renal scintigraphy in the 21st Century 99m Tc-MAG3 with zero time injection of furosemide (MAG3-F0): a fast and easy protocol, one for all indications. Part 3. Clinical experience. Congenital disorders

    International Nuclear Information System (INIS)

    Sfakianakis, G.N.

    2007-01-01

    In this work the Protocol for MAG 3 -F 0 is presented. Patient preparation, easy (only restriction, oral hydration, no bladder cathartic). Dynamic study (iv 1-10 mCi MAG 3 + 40-80 mg LASIX), simultaneous injection of furosemide: MAG 3 -F 0 , duration of the study: 25 minutes. Tomography-SPECT (20 mCi MAG 3 ). No diuretic needed, duration of the study: 4 minutes. (Author)

  14. Synaptic Correlates of Low-Level Perception in V1.

    Science.gov (United States)

    Gerard-Mercier, Florian; Carelli, Pedro V; Pananceau, Marc; Troncoso, Xoana G; Frégnac, Yves

    2016-04-06

    The computational role of primary visual cortex (V1) in low-level perception remains largely debated. A dominant view assumes the prevalence of higher cortical areas and top-down processes in binding information across the visual field. Here, we investigated the role of long-distance intracortical connections in form and motion processing by measuring, with intracellular recordings, their synaptic impact on neurons in area 17 (V1) of the anesthetized cat. By systematically mapping synaptic responses to stimuli presented in the nonspiking surround of V1 receptive fields, we provide the first quantitative characterization of the lateral functional connectivity kernel of V1 neurons. Our results revealed at the population level two structural-functional biases in the synaptic integration and dynamic association properties of V1 neurons. First, subthreshold responses to oriented stimuli flashed in isolation in the nonspiking surround exhibited a geometric organization around the preferred orientation axis mirroring the psychophysical "association field" for collinear contour perception. Second, apparent motion stimuli, for which horizontal and feedforward synaptic inputs summed in-phase, evoked dominantly facilitatory nonlinear interactions, specifically during centripetal collinear activation along the preferred orientation axis, at saccadic-like speeds. This spatiotemporal integration property, which could constitute the neural correlate of a human perceptual bias in speed detection, suggests that local (orientation) and global (motion) information is already linked within V1. We propose the existence of a "dynamic association field" in V1 neurons, whose spatial extent and anisotropy are transiently updated and reshaped as a function of changes in the retinal flow statistics imposed during natural oculomotor exploration. The computational role of primary visual cortex in low-level perception remains debated. The expression of this "pop-out" perception is often assumed

  15. CCR5 Disruption in Induced Pluripotent Stem Cells Using CRISPR/Cas9 Provides Selective Resistance of Immune Cells to CCR5-tropic HIV-1 Virus.

    Science.gov (United States)

    Kang, HyunJun; Minder, Petra; Park, Mi Ae; Mesquitta, Walatta-Tseyon; Torbett, Bruce E; Slukvin, Igor I

    2015-12-15

    The chemokine (C-C motif) receptor 5 (CCR5) serves as an HIV-1 co-receptor and is essential for cell infection with CCR5-tropic viruses. Loss of functional receptor protects against HIV infection. Here, we report the successful targeting of CCR5 in GFP-marked human induced pluripotent stem cells (iPSCs) using CRISPR/Cas9 with single and dual guide RNAs (gRNAs). Following CRISPER/Cas9-mediated gene editing using a single gRNA, 12.5% of cell colonies demonstrated CCR5 editing, of which 22.2% showed biallelic editing as determined by a Surveyor nuclease assay and direct sequencing. The use of dual gRNAs significantly increased the efficacy of CCR5 editing to 27% with a biallelic gene alteration frequency of 41%. To ensure the homogeneity of gene editing within cells, we used single cell sorting to establish clonal iPSC lines. Single cell-derived iPSC lines with homozygous CCR5 mutations displayed the typical characteristics of pluripotent stem cells and differentiated efficiently into hematopoietic cells, including macrophages. Although macrophages from both wild-type and CCR5-edited iPSCs supported CXCR4-tropic virus replication, macrophages from CCR5-edited iPSCs were uniquely resistant to CCR5-tropic virus challenge. This study demonstrates the feasibility of applying iPSC technology for the study of the role of CCR5 in HIV infection in vitro, and generation of HIV-resistant cells for potential therapeutic applications.

  16. Uma metodologia para parametrização do processo MIG/MAG CA A methodology for parameterization of the AC MIG/MAG process

    Directory of Open Access Journals (Sweden)

    Américo Scotti

    2012-09-01

    Full Text Available O processo MIG/MAG CA tem um potencial muito grande de aplicação, por permitir unir as características da soldagem MIG/MAG convencional (corrente contínua, com o eletrodo no positivo com as de se usar corrente negativa na soldagem MIG/MAG. Entretanto, o formato de onda de corrente (alternada, pulsada no positivo e constante no negativo demanda uma seleção criteriosa de seus inúmeros parâmetros de regulagem, o que vem limitando o estudo e aplicação desta versão de processo MIG/MAG. O objetivo deste trabalho foi propor e avaliar uma metodologia capaz de estimar os parâmetros de regulagem do processo MIG/MAG CA, de tal forma a se obter soldas com estabilidade de comprimento de arco e cordões com geometria adequada. É feita uma descrição passo a passo da definição dos parâmetros de entrada e da forma de se obter experimentalmente alguns valores de parâmetros necessários para estimação de outros valores de regulagem. As equações de estimação são apresentadas e discutidas. É feita uma demonstração da aplicação da metodologia, com a validação dos resultados pela comparação entre valores estimados e reais.The AC MIG/MAG process presents remarkable application potential, since it allows join the characteristics of the conventional MIG/MAG process (direct current, electrode positive with the ones obtained when negative current is applied in MIG/MAG welding. However, the current wave shape (alternate, pulsed in positive and constant in negative polarities demands a criterions selection of its innumerous setting parameters, fact that limits the development and application of this process version. The objective of this work was to propose and assess a methodology able to estimate the setting parameters of the CA MIG/MAG welding process, in such a way to result in welds with arc length stability and adequate bead geometry. A step-a-step description of the input parameter definitions and of the way to experimentally obtain

  17. The Efficacy of MAG-DHA for Correcting AA/DHA Imbalance of Cystic Fibrosis Patients

    Directory of Open Access Journals (Sweden)

    Caroline Morin

    2018-05-01

    Full Text Available Omega-3 polyunsaturated fatty acid (n-3 PUFA supplementations are thought to improve essential fatty acid deficiency (EFAD as well as reduce inflammation in Cystic Fibrosis (CF, but their effectiveness in clinical studies remains unknown. The aim of the study was to determine how the medical food containing docosahexaenoic acid monoglyceride (MAG-DHA influenced erythrocyte fatty acid profiles and the expression levels of inflammatory circulating mediators. We conducted a randomized, double blind, pilot trial including fifteen outpatients with Cystic Fibrosis, ages 18–48. The patients were divided into 2 groups and received MAG-DHA or a placebo (sunflower oil for 60 days. Patients took 8 × 625 mg MAG-DHA softgels or 8 × 625 mg placebo softgels every day at bedtime for 60 days. Lipid analyses revealed that MAG-DHA increased docosahexaenoic acid (DHA levels and decrease arachidonic acid (AA ratio (AA/DHA in erythrocytes of CF patients following 1 month of daily supplementation. Data also revealed a reduction in plasma human leukocyte elastase (pHLE complexes and interleukin-6 (IL-6 expression levels in blood samples of MAG-DHA supplemented CF patients. This pilot study indicates that MAG-DHA supplementation corrects erythrocyte AA/DHA imbalance and may exert anti-inflammatory properties through the reduction of pHLE complexes and IL6 in blood samples of CF patients. Trial registration: Pro-resolving Effect of MAG-DHA in Cystic Fibrosis (PREMDIC, NCT02518672.

  18. Antifibrotic Effects of the Dual CCR2/CCR5 Antagonist Cenicriviroc in Animal Models of Liver and Kidney Fibrosis.

    Directory of Open Access Journals (Sweden)

    Eric Lefebvre

    Full Text Available Interactions between C-C chemokine receptor types 2 (CCR2 and 5 (CCR5 and their ligands, including CCL2 and CCL5, mediate fibrogenesis by promoting monocyte/macrophage recruitment and tissue infiltration, as well as hepatic stellate cell activation. Cenicriviroc (CVC is an oral, dual CCR2/CCR5 antagonist with nanomolar potency against both receptors. CVC's anti-inflammatory and antifibrotic effects were evaluated in a range of preclinical models of inflammation and fibrosis.Monocyte/macrophage recruitment was assessed in vivo in a mouse model of thioglycollate-induced peritonitis. CCL2-induced chemotaxis was evaluated ex vivo on mouse monocytes. CVC's antifibrotic effects were evaluated in a thioacetamide-induced rat model of liver fibrosis and mouse models of diet-induced non-alcoholic steatohepatitis (NASH and renal fibrosis. Study assessments included body and liver/kidney weight, liver function test, liver/kidney morphology and collagen deposition, fibrogenic gene and protein expression, and pharmacokinetic analyses.CVC significantly reduced monocyte/macrophage recruitment in vivo at doses ≥20 mg/kg/day (p < 0.05. At these doses, CVC showed antifibrotic effects, with significant reductions in collagen deposition (p < 0.05, and collagen type 1 protein and mRNA expression across the three animal models of fibrosis. In the NASH model, CVC significantly reduced the non-alcoholic fatty liver disease activity score (p < 0.05 vs. controls. CVC treatment had no notable effect on body or liver/kidney weight.CVC displayed potent anti-inflammatory and antifibrotic activity in a range of animal fibrosis models, supporting human testing for fibrotic diseases. Further experimental studies are needed to clarify the underlying mechanisms of CVC's antifibrotic effects. A Phase 2b study in adults with NASH and liver fibrosis is fully enrolled (CENTAUR Study 652-2-203; NCT02217475.

  19. Structural refinement and prediction of potential CCR2 antagonists through validated multi-QSAR modeling studies.

    Science.gov (United States)

    Amin, Sk Abdul; Adhikari, Nilanjan; Baidya, Sandip Kumar; Gayen, Shovanlal; Jha, Tarun

    2018-01-03

    Chemokines trigger numerous inflammatory responses and modulate the immune system. The interaction between monocyte chemoattractant protein-1 and chemokine receptor 2 (CCR2) may be the cause of atherosclerosis, obesity, and insulin resistance. However, CCR2 is also implicated in other inflammatory diseases such as rheumatoid arthritis, multiple sclerosis, asthma, and neuropathic pain. Therefore, there is a paramount importance of designing potent and selective CCR2 antagonists despite a number of drug candidates failed in clinical trials. In this article, 83 CCR2 antagonists by Jhonson and Jhonson Pharmaceuticals have been considered for robust validated multi-QSAR modeling studies to get an idea about the structural and pharmacophoric requirements for designing more potent CCR2 antagonists. All these QSAR models were validated and statistically reliable. Observations resulted from different modeling studies correlated and validated results of other ones. Finally, depending on these QSAR observations, some new molecules were proposed that may exhibit higher activity against CCR2.

  20. Is distal motor and/or sensory demyelination a distinctive feature of anti-MAG neuropathy?

    Science.gov (United States)

    Lozeron, Pierre; Ribrag, Vincent; Adams, David; Brisset, Marion; Vignon, Marguerite; Baron, Marine; Malphettes, Marion; Theaudin, Marie; Arnulf, Bertrand; Kubis, Nathalie

    2016-09-01

    To report the frequency of the different patterns of sensory and motor electrophysiological demyelination distribution in patients with anti-MAG neuropathy in comparison with patients with IgM neuropathy without MAG reactivity (IgM-NP). Thirty-five anti-MAG patients at early disease stage (20.1 months) were compared to 23 patients with IgM-NP; 21 CIDP patients and 13 patients with CMT1a neuropathy were used as gold standard neuropathies with multifocal and homogeneous demyelination, respectively. In all groups, standard motor and sensory electrophysiological parameters, terminal latency index and modified F ratio were investigated. Motor electrophysiological demyelination was divided in four profiles: distal, homogeneous, proximal, and proximo-distal. Distal sensory and sensorimotor demyelination were evaluated. Anti-MAG neuropathy is a demyelinating neuropathy in 91 % of cases. In the upper limbs, reduced TLI is more frequent in anti-MAG neuropathy, compared to IgM-NP. But, predominant distal demyelination of the median nerve is encountered in only 43 % of anti-MAG neuropathy and is also common in IgM-NP (35 %). Homogeneous demyelination was the second most frequent pattern (31 %). Concordance of electrophysiological profiles across motor nerves trunks is low and median nerve is the main site of distal motor conduction slowing. Reduced sensory conduction velocities occurs in 14 % of patients without evidence of predominant distal slowing. Simultaneous sensory and motor distal slowing was more common in the median nerve of anti-MAG neuropathy than IgM-NP. Electrophysiological distal motor demyelination and sensory demyelination are not a distinctive feature of anti-MAG reactivity. In anti-MAG neuropathy it is mainly found in the median nerve suggesting a frequent nerve compression at wrist.

  1. Analysis of radiochemical purity (RCP) of 99Tcm-MAG3 injection

    International Nuclear Information System (INIS)

    Huang Qingquan; Xia Zhenmin

    1992-01-01

    A two-system paper chromatographic method has been established for the determination of RCP of 99 Tc m -MAG 3 injection. R f -values of 99 Tc m -MAG 3 , 99 Tc m O 4 - and H-R- 99 Tc m (hydrolysis reduced 99 Tc m ) are 0.9, 0.8, 0.0 in system I, and 0.0, 0.4, 0.0 in system II respectively. The RCP and percentages of 99 Tc m O 4 - and H-R- 99 Tc m of 99 Tc m -MAG 3 injection have been determined with this method

  2. CCR2 mediates Helicobacter pylori-induced immune tolerance and contributes to mucosal homeostasis.

    Science.gov (United States)

    Sun, Xia; Zhang, Min; El-Zaatari, Mohamad; Huffnagle, Gray B; Kao, John Y

    2017-04-01

    We previously demonstrated that H. pylori infection leads to increased induction of regulatory T cells in local and systemic immune compartments. Here, we investigate the role of CCR2 in the tolerogenic programing of dendritic cells in a mouse model of H. pylori infection. CCR2 deficient (CCR2KO) mice and wild-type (Wt) mice infected with H. pylori SS1 strain were analyzed by qPCR and FACS analysis. In vitro, bone marrow-derived DC on day 6 from CCR2KO and Wt mice cocultured with or without H. pylori were examined to determine the impact of CCR2 signaling on dendritic cells function by qPCR, ELISA, and FACS analyses. Acute H. pylori infection was associated with a threefold increase in CCR2 mRNA expression in the gastric mucosa. H. pylori-infected CCR2KO mice exhibited a higher degree of mucosal inflammation, that is, increased gastritis scores and pro-inflammatory cytokine mRNA levels, but lower degree of H. pylori gastric colonization compared to infected Wt mice. Peripheral H. pylori-specific immune response measured in the CCR2KO spleen was characterized by a higher Th17 response and a lower Treg response. In vitro, CCR2KO bone marrow-derived DC was less mature and shown a lower Treg/Th17 ratio. Moreover, blockade of CCR2 signaling by MCP-1 neutralizing antibody inhibited H. pylori-stimulated bone marrow-derived DC maturation. Our results indicate that CCR2 plays an essential role in H. pylori-induced immune tolerance and shed light on a novel mechanism of CCR2-dependent DC Treg induction, which appears to be important in maintaining mucosal homeostasis during H. pylori infection. © 2016 John Wiley & Sons Ltd.

  3. CCL2 recruits T cells into the brain in a CCR2-independent manner

    DEFF Research Database (Denmark)

    Cédile, Oriane; Wlodarczyk, Agnieszka; Owens, Trevor

    2017-01-01

    CCR2, a receptor for CCL2. Expression of another receptor for CCL2, CCR4, and CXCR3, a receptor for CXCL10, which was also induced, were both increased in CCL2-treated CNS. CCR4 was expressed by neurons and astrocytes as well as CD4 T cells, and CXCR3 was expressed by CD4 and CD8 T cells. Chemokine...

  4. The CCR4-NOT complex physically and functionally interacts with TRAMP and the nuclear exosome.

    Directory of Open Access Journals (Sweden)

    Nowel Azzouz

    Full Text Available BACKGROUND: Ccr4-Not is a highly conserved multi-protein complex consisting in yeast of 9 subunits, including Not5 and the major yeast deadenylase Ccr4. It has been connected functionally in the nucleus to transcription by RNA polymerase II and in the cytoplasm to mRNA degradation. However, there has been no evidence so far that this complex is important for RNA degradation in the nucleus. METHODOLOGY/PRINCIPAL FINDINGS: In this work we point to a new role for the Ccr4-Not complex in nuclear RNA metabolism. We determine the importance of the Ccr4-Not complex for the levels of non-coding nuclear RNAs, such as mis-processed and polyadenylated snoRNAs, whose turnover depends upon the nuclear exosome and TRAMP. Consistently, mutation of both the Ccr4-Not complex and the nuclear exosome results in synthetic slow growth phenotypes. We demonstrate physical interactions between the Ccr4-Not complex and the exosome. First, Not5 co-purifies with the exosome. Second, several exosome subunits co-purify with the Ccr4-Not complex. Third, the Ccr4-Not complex is important for the integrity of large exosome-containing complexes. Finally, we reveal a connection between the Ccr4-Not complex and TRAMP through the association of the Mtr4 helicase with the Ccr4-Not complex and the importance of specific subunits of Ccr4-Not for the association of Mtr4 with the nuclear exosome subunit Rrp6. CONCLUSIONS/SIGNIFICANCE: We propose a model in which the Ccr4-Not complex may provide a platform contributing to dynamic interactions between the nuclear exosome and its co-factor TRAMP. Our findings connect for the first time the different players involved in nuclear and cytoplasmic RNA degradation.

  5. Pulmonary CCR2+CD4+ T cells are immune regulatory and attenuate lung fibrosis development.

    Science.gov (United States)

    Milger, Katrin; Yu, Yingyan; Brudy, Eva; Irmler, Martin; Skapenko, Alla; Mayinger, Michael; Lehmann, Mareike; Beckers, Johannes; Reichenberger, Frank; Behr, Jürgen; Eickelberg, Oliver; Königshoff, Melanie; Krauss-Etschmann, Susanne

    2017-11-01

    Animal models have suggested that CCR2-dependent signalling contributes to the pathogenesis of pulmonary fibrosis, but global blockade of CCL2 failed to improve the clinical course of patients with lung fibrosis. However, as levels of CCR2 + CD4 + T cells in paediatric lung fibrosis had previously been found to be increased, correlating with clinical symptoms, we hypothesised that distinct CCR2 + cell populations might either increase or decrease disease pathogenesis depending on their subtype. To investigate the role of CCR2 + CD4 + T cells in experimental lung fibrosis and in patients with idiopathic pulmonary fibrosis and other fibrosis. Pulmonary CCR2 + CD4 + T cells were analysed using flow cytometry and mRNA profiling, followed by in silico pathway analysis, in vitro assays and adoptive transfer experiments. Frequencies of CCR2 + CD4 + T cells were increased in experimental fibrosis-specifically the CD62L - CD44 + effector memory T cell phenotype, displaying a distinct chemokine receptor profile. mRNA profiling of isolated CCR2 + CD4 + T cells from fibrotic lungs suggested immune regulatory functions, a finding that was confirmed in vitro using suppressor assays. Importantly, adoptive transfer of CCR2 + CD4 + T cells attenuated fibrosis development. The results were partly corroborated in patients with lung fibrosis, by showing higher percentages of Foxp3 + CD25 + cells within bronchoalveolar lavage fluid CCR2 + CD4 + T cells as compared with CCR2 - CD4 + T cells. Pulmonary CCR2 + CD4 + T cells are immunosuppressive, and could attenuate lung inflammation and fibrosis. Therapeutic strategies completely abrogating CCR2-dependent signalling will therefore also eliminate cell populations with protective roles in fibrotic lung disease. This emphasises the need for a detailed understanding of the functions of immune cell subsets in fibrotic lung disease. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights

  6. Limited protective effect of the CCR5Delta32/CCR5Delta32 genotype on human immunodeficiency virus infection incidence in a cohort of patients with hemophilia and selection for genotypic X4 virus

    DEFF Research Database (Denmark)

    Iversen, Astrid K N; Christiansen, Claus Bohn; Attermann, Jørn

    2003-01-01

    The relationship among CCR5 genotype, cytomegalovirus infection, and disease progression and death was studied among 159 human immunodeficiency virus (HIV)-infected patients with hemophilia. One patient (0.6%) had the CCR5Delta32/CCR5Delta32 genotype (which occurs in approximately 2% of the Scand......The relationship among CCR5 genotype, cytomegalovirus infection, and disease progression and death was studied among 159 human immunodeficiency virus (HIV)-infected patients with hemophilia. One patient (0.6%) had the CCR5Delta32/CCR5Delta32 genotype (which occurs in approximately 2...

  7. CCR5 delta32, matrix metalloproteinase-9 and disease activity in multiple sclerosis

    DEFF Research Database (Denmark)

    Sellebjerg, Finn; Madsen, Hans O; Jensen, Claus V

    2000-01-01

    Chemokines and matrix metalloproteinases (MMPs) appear to be crucial in leukocyte recruitment to the central nervous system in multiple sclerosis (MS). CCR5 delta32, a truncated allele of the CC chemokine receptor CCR5 gene encoding a non-functional receptor, did not confer protection from MS. CCR5...... delta32 was, however, associated with a lower risk of recurrent clinical disease activity. High CSF levels of MMP-9 activity were also associated with recurrent disease activity. These results directly link intrathecal inflammation to disease activity in patients with MS, suggesting that treatments...... targeting CCR5 or treatment with MMP inhibitors may attenuate disease activity in MS...

  8. Dengue virus requires the CC-chemokine receptor CCR5 for replication and infection development.

    Science.gov (United States)

    Marques, Rafael E; Guabiraba, Rodrigo; Del Sarto, Juliana L; Rocha, Rebeca F; Queiroz, Ana Luiza; Cisalpino, Daniel; Marques, Pedro E; Pacca, Carolina C; Fagundes, Caio T; Menezes, Gustavo B; Nogueira, Maurício L; Souza, Danielle G; Teixeira, Mauro M

    2015-08-01

    Dengue is a mosquito-borne disease that affects millions of people worldwide yearly. Currently, there is no vaccine or specific treatment available. Further investigation on dengue pathogenesis is required to better understand the disease and to identify potential therapeutic targets. The chemokine system has been implicated in dengue pathogenesis, although the specific role of chemokines and their receptors remains elusive. Here we describe the role of the CC-chemokine receptor CCR5 in Dengue virus (DENV-2) infection. In vitro experiments showed that CCR5 is a host factor required for DENV-2 replication in human and mouse macrophages. DENV-2 infection induces the expression of CCR5 ligands. Incubation with an antagonist prevents CCR5 activation and reduces DENV-2 positive-stranded (+) RNA inside macrophages. Using an immunocompetent mouse model of DENV-2 infection we found that CCR5(-/-) mice were resistant to lethal infection, presenting at least 100-fold reduction of viral load in target organs and significant reduction in disease severity. This phenotype was reproduced in wild-type mice treated with CCR5-blocking compounds. Therefore, CCR5 is a host factor required for DENV-2 replication and disease development. Targeting CCR5 might represent a therapeutic strategy for dengue fever. These data bring new insights on the association between viral infections and the chemokine receptor CCR5. © 2015 John Wiley & Sons Ltd.

  9. Deficient Fas expression by CD4+ CCR5+ T cells in multiple sclerosis

    DEFF Research Database (Denmark)

    Julià, Eva; Montalban, Xavier; Al-Zayat, Hammad

    2006-01-01

    OBJECTIVE: To evaluate whether T cells expressing CCR5 and CXCR3 from multiple sclerosis (MS) patients are more resistant to apoptosis. METHODS: Expression of CD69, TNF-R1, Fas, FasL, bcl-2, and bax was investigated in 41 MS patients and 12 healthy controls by flow cytometry in CD4+ and CD8+ T...... cells expressing CCR5 and CXCR3. RESULTS: In MS patients, the percentage of CD69 was increased and Fas expression decreased in CD4+ CCR5+ T cells. INTERPRETATION: The lower Fas expression in activated CD4+ CCR5+ T cells might contribute to disease pathogenesis by prolonging cell survival and favoring...

  10. Chemokine Receptor Ccr1 Drives Neutrophil-Mediated Kidney Immunopathology and Mortality in Invasive Candidiasis

    Science.gov (United States)

    Lionakis, Michail S.; Swamydas, Muthulekha; Wan, Wuzhou; Richard Lee, Chyi-Chia; Cohen, Jeffrey I.; Scheinberg, Phillip; Gao, Ji-Liang; Murphy, Philip M.

    2012-01-01

    Invasive candidiasis is the 4th leading cause of nosocomial bloodstream infection in the US with mortality that exceeds 40% despite administration of antifungal therapy; neutropenia is a major risk factor for poor outcome after invasive candidiasis. In a fatal mouse model of invasive candidiasis that mimics human bloodstream-derived invasive candidiasis, the most highly infected organ is the kidney and neutrophils are the major cellular mediators of host defense; however, factors regulating neutrophil recruitment have not been previously defined. Here we show that mice lacking chemokine receptor Ccr1, which is widely expressed on leukocytes, had selectively impaired accumulation of neutrophils in the kidney limited to the late phase of the time course of the model; surprisingly, this was associated with improved renal function and survival without affecting tissue fungal burden. Consistent with this, neutrophils from wild-type mice in blood and kidney switched from Ccr1lo to Ccr1high at late time-points post-infection, when Ccr1 ligands were produced at high levels in the kidney and were chemotactic for kidney neutrophils ex vivo. Further, when a 1∶1 mixture of Ccr1+/+ and Ccr1−/− donor neutrophils was adoptively transferred intravenously into Candida-infected Ccr1+/+ recipient mice, neutrophil trafficking into the kidney was significantly skewed toward Ccr1+/+ cells. Thus, neutrophil Ccr1 amplifies late renal immunopathology and increases mortality in invasive candidiasis by mediating excessive recruitment of neutrophils from the blood to the target organ. PMID:22916017

  11. CCR5 is a suppressor for cortical plasticity and hippocampal learning and memory.

    Science.gov (United States)

    Zhou, Miou; Greenhill, Stuart; Huang, Shan; Silva, Tawnie K; Sano, Yoshitake; Wu, Shumin; Cai, Ying; Nagaoka, Yoshiko; Sehgal, Megha; Cai, Denise J; Lee, Yong-Seok; Fox, Kevin; Silva, Alcino J

    2016-12-20

    Although the role of CCR5 in immunity and in HIV infection has been studied widely, its role in neuronal plasticity, learning and memory is not understood. Here, we report that decreasing the function of CCR5 increases MAPK/CREB signaling, long-term potentiation (LTP), and hippocampus-dependent memory in mice, while neuronal CCR5 overexpression caused memory deficits. Decreasing CCR5 function in mouse barrel cortex also resulted in enhanced spike timing dependent plasticity and consequently, dramatically accelerated experience-dependent plasticity. These results suggest that CCR5 is a powerful suppressor for plasticity and memory, and CCR5 over-activation by viral proteins may contribute to HIV-associated cognitive deficits. Consistent with this hypothesis, the HIV V3 peptide caused LTP, signaling and memory deficits that were prevented by Ccr5 knockout or knockdown. Overall, our results demonstrate that CCR5 plays an important role in neuroplasticity, learning and memory, and indicate that CCR5 has a role in the cognitive deficits caused by HIV.

  12. CCR5 internalisation and signalling have different dependence on membrane lipid raft integrity.

    Science.gov (United States)

    Cardaba, Clara Moyano; Kerr, Jason S; Mueller, Anja

    2008-09-01

    The chemokine receptor, CCR5, acts as a co-receptor for human immunodeficiency virus entry into cells. CCR5 has been shown to be targeted to cholesterol- and sphingolipid-rich membrane microdomains termed lipid rafts or caveolae. Cholesterol is essential for CCL4 binding to CCR5 and for keeping the conformational integrity of the receptor. Filipin treatment leads to loss of caveolin-1 from the membrane and therefore to a collapse of the caveolae. We have found here that sequestration of membrane cholesterol with filipin did not affect receptor signalling, however a loss of ligand-induced internalisation of CCR5 was observed. Cholesterol extraction with methyl-beta-cyclodextrin (MCD) reduced signalling through CCR5 as measured by release of intracellular Ca(2+) and completely abolished the inhibition of forskolin-stimulated cAMP accumulation with no effect on internalisation. Pertussis toxin (PTX) treatment inhibited the intracellular release of calcium that is transduced via Galphai G-proteins. Depletion of cholesterol destroyed microdomains in the membrane and switched CCR5/G-protein coupling to a PTX-independent G-protein. We conclude that cholesterol in the membrane is essential for CCR5 signalling via the Galphai G-protein subunit, and that integrity of lipid rafts is not essential for effective CCR5 internalisation however it is crucial for proper CCR5 signal transduction via Galphai G-proteins.

  13. Inhibition of human immunodeficiency virus replication by a dual CCR5/CXCR4 antagonist

    DEFF Research Database (Denmark)

    Princen, Katrien; Hatse, Sigrid; Vermeire, Kurt

    2004-01-01

    Here we report that the N-pyridinylmethyl cyclam analog AMD3451 has antiviral activity against a wide variety of R5, R5/X4, and X4 strains of human immunodeficiency virus type 1 (HIV-1) and HIV-2 (50% inhibitory concentration [IC(50)] ranging from 1.2 to 26.5 microM) in various T-cell lines, CCR5...... at the virus entry stage. AMD3451 dose-dependently inhibited the intracellular Ca(2+) signaling induced by the CXCR4 ligand CXCL12 in T-lymphocytic cells and in CXCR4-transfected cells, as well as the Ca(2+) flux induced by the CCR5 ligands CCL5, CCL3, and CCL4 in CCR5-transfected cells. The compound did...... not interfere with chemokine-induced Ca(2+) signaling through CCR1, CCR2, CCR3, CCR4, CCR6, CCR9, or CXCR3 and did not induce intracellular Ca(2+) signaling by itself at concentrations up to 400 microM. In freshly isolated monocytes, AMD3451 inhibited the Ca(2+) flux induced by CXCL12 and CCL4...

  14. Chemokine receptor Ccr1 drives neutrophil-mediated kidney immunopathology and mortality in invasive candidiasis.

    Directory of Open Access Journals (Sweden)

    Michail S Lionakis

    Full Text Available Invasive candidiasis is the 4(th leading cause of nosocomial bloodstream infection in the US with mortality that exceeds 40% despite administration of antifungal therapy; neutropenia is a major risk factor for poor outcome after invasive candidiasis. In a fatal mouse model of invasive candidiasis that mimics human bloodstream-derived invasive candidiasis, the most highly infected organ is the kidney and neutrophils are the major cellular mediators of host defense; however, factors regulating neutrophil recruitment have not been previously defined. Here we show that mice lacking chemokine receptor Ccr1, which is widely expressed on leukocytes, had selectively impaired accumulation of neutrophils in the kidney limited to the late phase of the time course of the model; surprisingly, this was associated with improved renal function and survival without affecting tissue fungal burden. Consistent with this, neutrophils from wild-type mice in blood and kidney switched from Ccr1(lo to Ccr1(high at late time-points post-infection, when Ccr1 ligands were produced at high levels in the kidney and were chemotactic for kidney neutrophils ex vivo. Further, when a 1∶1 mixture of Ccr1(+/+ and Ccr1(-/- donor neutrophils was adoptively transferred intravenously into Candida-infected Ccr1(+/+ recipient mice, neutrophil trafficking into the kidney was significantly skewed toward Ccr1(+/+ cells. Thus, neutrophil Ccr1 amplifies late renal immunopathology and increases mortality in invasive candidiasis by mediating excessive recruitment of neutrophils from the blood to the target organ.

  15. CCR6(+) Th cell populations distinguish ACPA positive from ACPA negative rheumatoid arthritis.

    Science.gov (United States)

    Paulissen, Sandra M J; van Hamburg, Jan Piet; Davelaar, Nadine; Vroman, Heleen; Hazes, Johanna M W; de Jong, Pascal H P; Lubberts, Erik

    2015-11-30

    Patients with rheumatoid arthritis (RA) can be separated into two major subpopulations based on the absence or presence of serum anti-citrullinated protein antibodies (ACPAs). The more severe disease course in ACPA(+) RA and differences in treatment outcome between these subpopulations suggest that ACPA(+) and ACPA(-) RA are different disease subsets. The identification of T-helper (Th) cells specifically recognizing citrullinated peptides, combined with the strong association between HLA-DRB1 and ACPA positivity, point toward a pathogenic role of Th cells in ACPA(+) RA. In this context we recently identified a potential pathogenic role for CCR6(+) Th cells in RA. Therefore, we examined whether Th cell population distributions differ by ACPA status. We performed a nested matched case-control study including 27 ACPA(+) and 27 ACPA(-) treatment-naive early RA patients matched for disease activity score in 44 joints, presence of rheumatoid factor, sex, age, duration of complaints and presence of erosions. CD4(+)CD45RO(+) (memory) Th cell distribution profiles from these patients were generated based on differential chemokine receptor expression and related with disease duration. ACPA status was not related to differences in total CD4(+) T cell or memory Th cell proportions. However, ACPA(+) patients had significantly higher proportions of Th cells expressing the chemokine receptors CCR6 and CXCR3. Similar proportions of CCR4(+) and CCR10(+) Th cells were found. Within the CCR6(+) cell population, four Th subpopulations were distinguished based on differential chemokine receptor expression: Th17 (CCR4(+)CCR10(-)), Th17.1 (CXCR3(+)), Th22 (CCR4(+)CCR10(+)) and CCR4/CXCR3 double-positive (DP) cells. In particular, higher proportions of Th22 (p = 0.02), Th17.1 (p = 0.03) and CCR4/CXCR3 DP (p = 0.01) cells were present in ACPA(+) patients. In contrast, ACPA status was not associated with differences in Th1 (CCR6(-)CXCR3(+); p = 0.90), Th2 (CCR6(-)CCR4(+); p = 0.27) and T

  16. Comet P/2010 V1 as a Natural Disintegration Laboratory

    Science.gov (United States)

    Jewitt, David; Weaver, Harold A.; Mutchler, Maximilian J.; Agarwal, Jessica; Meech, Karen Jean; Li, Jing; Kleyna, Jan; Ishiguro, Masateru; Wainscoat, Richard J.; Hui, Man-To

    2016-10-01

    Discovered in outburst in 2010, Jupiter-family comet P/2010 V1 (Ikeya-Murukami) was found to be split in observations at the end of 2015. We used the Hubble Space Telescope to obtain deep images of P/2010 V1 at high angular resolution in the 2016 January to March period. The resulting data, by far the best yet obtained for any split or disrupting comet, show the astrometric, photometric and morphological evolution of about 30 fragments. We will present the first results for the velocity dispersion, photometric distribution and variability and discuss the measurements in terms of models for the breakup.

  17. Masking interrupts figure-ground signals in V1.

    Science.gov (United States)

    Lamme, Victor A F; Zipser, Karl; Spekreijse, Henk

    2002-10-01

    In a backward masking paradigm, a target stimulus is rapidly (figure-ground segregation can be recorded. Here, we recorded from awake macaque monkeys, engaged in a task where they had to detect figures from background in a pattern backward masking paradigm. We show that the V1 figure-ground signals are selectively and fully suppressed at target-mask intervals that psychophysically result in the target being invisible. Initial response transients, signalling the features that make up the scene, are not affected. As figure-ground modulations depend on feedback from extrastriate areas, these results suggest that masking selectively interrupts the recurrent interactions between V1 and higher visual areas.

  18. Investigação e desenvolvimento do processo MIG/MAG com arame adicional

    OpenAIRE

    Mogrovejo, Miguel Guayasamin

    2014-01-01

    Dissertação (mestrado) - Universidade Federal de Santa Catarina, Centro Tecnológico, Programa de Pós-Graduação em Engenharia Mecânica, Florianópolis, 2014 Este trabalho apresenta as relações e aspectos técnicos para desenvolvimento de uma variante do processo MIG/MAG que procura o incremento da produtividade sem comprometer a qualidade. A base da questão é o fato de que no processo MIG/MAG na configuração convencional, apesar de suas nuances de versões como o MIG/MAG CC- ou MIG/MAG CA, a r...

  19. IgM MGUS associated with anti-MAG neuropathy: a single institution experience.

    Science.gov (United States)

    Talamo, Giampaolo; Mir, Muhammad A; Pandey, Manoj K; Sivik, Jeffrey K; Raheja, Divisha

    2015-06-01

    Anti-MAG neuropathy is a very rare form of acquired polyneuropathy associated with IgM monoclonal gammopathy of undetermined significance (MGUS). We conducted a retrospective review of 194 consecutive MGUS patients seen at the Penn State Hershey Cancer Institute. We identified six patients among 37 (16 %) with IgM MGUS with anti-MAG neuropathy. Interestingly, an additional patient had anti-MAG neuropathy without MGUS. Common clinical manifestations were numbness and paresthesias of the extremities and gait imbalance. All four patients treated with rituximab and none of the three untreated ones had a subjective improvement of their symptoms. We conclude that all patients with IgM MGUS and neuropathy should be screened for anti-MAG antibodies and, if positive, they should be offered treatment with rituximab.

  20. Wounds caused by contact with muzzle-lift relief ports (Mag-Na-Port).

    Science.gov (United States)

    Rogers, D R; Shem, R J

    1992-12-01

    Fan-shaped stippled burns were produced on the skin when a revolver whose barrel had been modified by the Mag-Na-Port process was fired twice with the side of the muzzle in contact. A grazing wound was produced by one bullet, and an oblique entry was produced by the other. The characteristics of Mag-Na-Port wounds and test shots are described, and these are compared with test shots from two other higher power revolvers.

  1. Feasibility of MR imaging in evaluating breast cancer lymphangiogenesis using Polyethylene glycol-GoldMag nanoparticles

    International Nuclear Information System (INIS)

    Yang, H.; Zou, L.G.; Zhang, S.; Gong, M.F.; Zhang, D.; Qi, Y.Y.; Zhou, S.W.; Diao, X.W.

    2013-01-01

    Aim: To investigate the feasibility of evaluating tumour lymphangiogenesis using magnetic resonance imaging (MRI) in vivo. Materials and methods: Water-soluble polyethylene glycol (PEG)-GoldMag nanoparticles were obtained by combining GoldMag with PEG. The PEG-GoldMag nanoparticles were bound to anti-podoplanin antibody (PodAb) to construct PEG-GoldMag-pod molecular probes targeting lymphatic endothelial cells (LECs). The characteristics of the PEG-GoldMag-pod nanoparticles were tested. Using these nanoparticles, tumour lymphangiogenesis was evaluated using MRI in vitro and in vivo. Results: The average size of PEG-GoldMag nanoparticles was about 66.8 nm, and the nanoparticles were stably dispersed in the liquid phase for at least 15 days. After incubation for 24 h at different iron concentrations ranging from 5–45 μg/ml, the LECs were labelled with PEG-GoldMag-pod nanoparticles, in particular the breast cancer LECs. Dose-dependence was observed in the labelling efficiencies and MRI images of the labelled cells. In vitro, the labelling efficiencies and MRI images showed that the nanoparticles could detect podoplanin expression in LECs. In induced rat models of breast cancer, PEG-GoldMag-pod nanoparticles combined with lymphatic vessels were significantly detectable at MRI 60 min after nanoparticle administration, the signal intensity was negatively correlated with the lymphatic vessel density of breast cancer (r = −0.864, P = 0.000). Conclusions: The present study proves the feasibility of evaluating tumour lymphangiogenesis with MRI in vivo

  2. Evaluation of renal function using 99mTc-MAG3

    International Nuclear Information System (INIS)

    Takayama, Teruhiko; Aburano, Tamio; Shuke, Noriyuki

    1993-01-01

    The utility of 99m Tc-mercaptoacetyltriglycine (MAG3) was studied clinically. In the renography obtained with 99m Tc-MAG3, the abdominal aorta and the common iliac arteries were clearly visualized in the vascular phase. Due to less background activity and high target to background ratio, the quality of 99m Tc-MAG3 image was superior to that of 123 I-OIH or 99m Tc-DTPA image. The parameters on the renogram including T max , T 2/3 , and T 1/2 were compared. The correlation of T max and T 2/3 or T 1/2 were not significant between 99m Tc-MAG3 and 123 I-OIH. Another parameter of C 20 /C max , where C 20 and C max are renal activities at 20 min after injection and at T max respectively, showed an excellent correlation between 99m Tc-MAG3 and 123 I-OIH. Using C 20 /C max , pattern of renogram can be characterized numerically. Concerning the relation between C 20 /C max and renogram pattern, standard renogram pattern showed the C 20 /C max value of less than 0.4, while hypofunctioning pattern showed more than 0.5. The correlation coefficient between the renal uptake of 99m Tc-MAG3 and 123 I-OIH was 0.880 with a correlation plot: 'Y=1.16X-0.043', where X and Y represent renal uptake of 99m Tc-MAG3 and 123 I-OIH, respectively. It can be concluded that 99m Tc-MAG3 is a useful renal imaging agent as an alternative to 123 I-OIH, in order to evaluate the proximal tubular function and calculate ERPF. (author)

  3. Narcolepsy susceptibility gene CCR3 modulates sleep-wake patterns in mice.

    Directory of Open Access Journals (Sweden)

    Hiromi Toyoda

    Full Text Available Narcolepsy is caused by the loss of hypocretin (Hcrt neurons and is associated with multiple genetic and environmental factors. Although abnormalities in immunity are suggested to be involved in the etiology of narcolepsy, no decisive mechanism has been established. We previously reported chemokine (C-C motif receptor 3 (CCR3 as a novel susceptibility gene for narcolepsy. To understand the role of CCR3 in the development of narcolepsy, we investigated sleep-wake patterns of Ccr3 knockout (KO mice. Ccr3 KO mice exhibited fragmented sleep patterns in the light phase, whereas the overall sleep structure in the dark phase did not differ between Ccr3 KO mice and wild-type (WT littermates. Intraperitoneal injection of lipopolysaccharide (LPS promoted wakefulness and suppressed both REM and NREM sleep in the light phase in both Ccr3 KO and WT mice. Conversely, LPS suppressed wakefulness and promoted NREM sleep in the dark phase in both genotypes. After LPS administration, the proportion of time spent in wakefulness was higher, and the proportion of time spent in NREM sleep was lower in Ccr3 KO compared to WT mice only in the light phase. LPS-induced changes in sleep patterns were larger in Ccr3 KO compared to WT mice. Furthermore, we quantified the number of Hcrt neurons and found that Ccr3 KO mice had fewer Hcrt neurons in the lateral hypothalamus compared to WT mice. We found abnormalities in sleep patterns in the resting phase and in the number of Hcrt neurons in Ccr3 KO mice. These observations suggest a role for CCR3 in sleep-wake regulation in narcolepsy patients.

  4. Blocking spinal CCR2 with AZ889 reversed hyperalgesia in a model of neuropathic pain

    Directory of Open Access Journals (Sweden)

    Vaillancourt François

    2010-12-01

    Full Text Available Abstract Background The CCR2/CCL2 system has been identified as a regulator in the pathogenesis of neuropathy-induced pain. However, CCR2 target validation in analgesia and the mechanism underlying antinociception produced by CCR2 antagonists remains poorly understood. In this study, in vitro and in vivo pharmacological approaches using a novel CCR2 antagonist, AZ889, strengthened the hypothesis of a CCR2 contribution to neuropathic pain and provided confidence over the possibilities to treat neuropathic pain with CCR2 antagonists. Results We provided evidence that dorsal root ganglia (DRG cells harvested from CCI animals responded to stimulation by CCL2 with a concentration-dependent calcium rise involving PLC-dependent internal stores. This response was associated with an increase in evoked neuronal action potentials suggesting these cells were sensitive to CCR2 signalling. Importantly, treatment with AZ889 abolished CCL2-evoked excitation confirming that this activity is CCR2-mediated. Neuronal and non-neuronal cells in the spinal cord were also excited by CCL2 applications indicating an important role of spinal CCR2 in neuropathic pain. We next showed that in vivo spinal intrathecal injection of AZ889 produced dose-dependent analgesia in CCI rats. Additionally, application of AZ889 to the exposed spinal cord inhibited evoked neuronal activity and confirmed that CCR2-mediated analgesia involved predominantly the spinal cord. Furthermore, AZ889 abolished NMDA-dependent wind-up of spinal withdrawal reflex pathway in neuropathic animals giving insight into the spinal mechanism underlying the analgesic properties of AZ889. Conclusions Overall, this study strengthens the important role of CCR2 in neuropathic pain and highlights feasibility that interfering on this mechanism at the spinal level with a selective antagonist can provide new analgesia opportunities.

  5. Increased brain damage after ischaemic stroke in mice lacking the chemokine receptor CCR5

    Science.gov (United States)

    Sorce, S; Bonnefont, J; Julien, S; Marq-Lin, N; Rodriguez, I; Dubois-Dauphin, M; Krause, KH

    2010-01-01

    Background and purpose: The chemokine receptor CCR5 is well known for its function in immune cells; however, it is also expressed in the brain, where its specific role remains to be elucidated. Because genetic factors may influence the risk of developing cerebral ischaemia or affect its clinical outcome, we have analysed the role of CCR5 in experimental stroke. Experimental approach: Permanent cerebral ischaemia was performed by occlusion of the middle cerebral artery in wild-type and CCR5-deficient mice. Locomotor behaviour, infarct size and histochemical alterations were analysed at different time points after occlusion. Key results: The cerebral vasculature was comparable in wild-type and CCR5-deficient mice. However, the size of the infarct and the motor deficits after occlusion were markedly increased in CCR5-deficient mice as compared with wild type. No differences between wild-type and CCR5-deficient mice were elicited by occlusion with respect to the morphology and abundance of astrocytes and microglia. Seven days after occlusion the majority of CCR5-deficient mice displayed neutrophil invasion in the infarct region, which was not observed in wild type. As compared with wild type, the infarct regions of CCR5-deficient mice were characterized by increased neuronal death. Conclusions and implications: Lack of CCR5 increased the severity of brain injury following occlusion of the middle cerebral artery. This is of particular interest with respect to the relatively frequent occurrence of CCR5 deficiency in the human population (1–2% of the Caucasian population) and the advent of CCR5 inhibitors as novel drugs. PMID:20423342

  6. Expression of human mag-1 gene in E. coli and preparation of its antibody

    International Nuclear Information System (INIS)

    Lin Huiyun; Xu Yuanji; Wang Yan; Chen Huihua; Du Zhiyan; Tan Xiaogang; Lu Yinglin

    2006-01-01

    Objective: To further investigate the new metastasis associated gene, mag-1 expressed in E. coli and its anti-body was prepared in rabbit. Methods: mag-1 was amplified by PCR from pcDNA3-mag-1 and directly cloned into pET-28a vector. The fusion protein was expressed in BL21 and identified by Western blot using anti-His monoclonal antibody. Rabbit was immunized with partially purified fusion protein subcutaneously. Results: Sequence analysis revealed identity of the sequence obtained to the previous report. The recombinant His-mag-1 could be expressed in E. coli as a fusion protein of 18 x 10 3 . The recombinant protein was mostly expressed in the inclusion bodies on the induction by 0.1 mmol/L IPTG at 37 degree C for 6 hours. Western blot analysis showed that the recombinant protein could be recognized by His monoclonal anti-body. The titer of polyclonal antibody against mag-1 was 1:160000. Conclusion: The mag-1 gene is expressed in E. coli highly and its antibody is prepared successfully. (authors)

  7. The MagOrion - A propulsion system for human exploration of the outer planets

    International Nuclear Information System (INIS)

    Andrews, Jason; Andrews, Dana

    2000-01-01

    Manned exploration beyond Mars requires very high specific energy. The only potential solution under discussion is fusion propulsion. However, fusion has been ten years away for forty years. We have an available solution that combines new technology with an old concept-'Project Orion'. The proposed 'MagOrion' Propulsion System combines a magnetic sail (MagSail) with conventional small yield (0.5 to 1.0 kiloton) shaped nuclear fission devices. At denonation, roughly eighty percent of the yield appears as a highly-ionized plasma, and when detonated two kilometers behind a robust MagSail, approximately half of this plasma can be stopped and turned into thrust. A MagOrion can provide a system acceleration of one or more gravities with effective specific impulses ranging from 15,000 to 45,000 seconds. Dana Andrews and Robert Zubrin published a paper in 1997 that described the operating principles of the MagOrion. We have taken that concept through conceptual design to identify the major operational features and risks. The risks are considerable, but the potential payoff is staggering. Our proposed MagOrion will enable affordable exploration of the solar system

  8. Study of brain atrophy using X-ray computed tomography. Measurement of CSF space-cranial cavity ratio (CCR)

    Energy Technology Data Exchange (ETDEWEB)

    Kawabata, Masayoshi

    1987-04-01

    Cerebrospinal fluid space-cranial cavity ratio (CCR) of 811 subjects with no brain damage were investigated using X-ray computed tomography. Brain volume of healthy adults aged 20 - 59 years was almost constant and decreased gradually after 60 years. CCR of men aged 20 - 49 years kept constant value and increased with aging after 50 years. CCR of women aged 20 - 59 years kept equal value and CCR increased with aging after 60 years. Brain atrophy with aging was investigated in this study also. In retrospective study, CCR of patients in any age diagnosed brain atrophy in daily CT reports were beyond the normal range of CCR of healthy subjects aged 20 - 49 years. In 48 patients with Parkinson's disease, almost of CCR of them were included within normal range of CCR in age-matched control.

  9. 77 FR 55833 - Announcement of Public Meeting on the Consumer Confidence Report (CCR) Rule Retrospective Review...

    Science.gov (United States)

    2012-09-11

    ... on the Consumer Confidence Report (CCR) Rule Retrospective Review and Request for Public Comment on... potential approaches for providing Consumer Confidence Reports (CCR) via electronic delivery. EPA plans to... meeting to give EPA time to process your request. Background Consumer Confidence Reports are a key part of...

  10. 77 FR 57566 - Announcement of Public Meeting on the Consumer Confidence Report (CCR) Rule Retrospective Review...

    Science.gov (United States)

    2012-09-18

    ... ENVIRONMENTAL PROTECTION AGENCY [EPA-HQ-OW-2012-0035; FRL-9730-7] Announcement of Public Meeting on the Consumer Confidence Report (CCR) Rule Retrospective Review and Request for Public Comment on Potential Approaches to Electronic Delivery of the CCR; Correction AGENCY: Environmental Protection Agency...

  11. Biased small-molecule ligands for selective inhibition of HIV-1 cell entry via CCR5

    DEFF Research Database (Denmark)

    Berg, Christian; Spiess, Katja; von Lüttichau, Hans Rudolf

    2016-01-01

    Since the discovery of HIV's use of CCR5 as the primary coreceptor in fusion, the focus on developing small-molecule receptor antagonists for inhibition hereof has only resulted in one single drug, Maraviroc. We therefore investigated the possibility of using small-molecule CCR5 agonists as HIV-1...

  12. Chemokine Receptor CCR5 Antagonist Maraviroc: Medicinal Chemistry and Clinical Applications

    Science.gov (United States)

    Xu, Guoyan G.; Guo, Jia; Wu, Yuntao

    2015-01-01

    The human immunodeficiency virus (HIV) causes acquired immumodeficiency syndrome (AIDS), one of the worst global pandemic. The virus infects human CD4 T cells and macrophages, and causes CD4 depletion. HIV enters target cells through the binding of the viral envelope glycoprotein to CD4 and the chemokine coreceptor, CXCR4 or CCR5. In particular, the CCR5-utilizing viruses predominate in the blood during the disease course. CCR5 is expressed on the surface of various immune cells including macrophages, monocytes, microglia, dendric cells, and active memory CD4 T cells. In the human population, the CCR5 genomic mutation, CCR5Δ32, is associated with relative resistance to HIV. These findings paved the way for the discovery and development of CCR5 inhibitors to block HIV transmission and replication. Maraviroc, discovered as a CCR5 antagonist, is the only CCR5 inhibitor that has been approved by both US FDA and the European Medicines Agency (EMA) for treating HIV/AIDS patients. In this review, we summarize the medicinal chemistry and clinical studies of Maraviroc. PMID:25159165

  13. Profile of State College and Career Readiness Assessments (CCR) Policy. Florida

    Science.gov (United States)

    Center on Education Policy, 2011

    2011-01-01

    This individual profile provides information on Florida's college and career readiness assessment policy. Some of the categories presented include: (1) CCR assessment policy; (2) Purpose; (3) Major changes in CCR assessment policy since the 2009-10 school year for financial reasons; (4) State financial support for students to take the CCR…

  14. Profile of State College and Career Readiness Assessments (CCR) Policy. Arkansas

    Science.gov (United States)

    Center on Education Policy, 2011

    2011-01-01

    This individual profile provides information on Arkansas' college and career readiness assessment policy. Some of the categories presented include: (1) CCR assessment policy; (2) Purpose; (3) Major changes in CCR assessment policy since the 2009-10 school year for financial reasons; (4) State financial support for students to take the CCR…

  15. Profile of State College and Career Readiness Assessments (CCR) Policy. Minnesota

    Science.gov (United States)

    Center on Education Policy, 2011

    2011-01-01

    This individual profile provides information on Minnesota's college and career readiness assessment policy. Some of the categories presented include: (1) CCR assessment policy; (2) Purpose; (3) Major changes in CCR assessment policy since the 2009-10 school year for financial reasons; (4) State financial support for students to take the CCR…

  16. Profile of State College and Career Readiness Assessments (CCR) Policy. Alaska

    Science.gov (United States)

    Center on Education Policy, 2011

    2011-01-01

    This individual profile provides information on Alaska's college and career readiness assessment policy. Some of the categories presented include: (1) CCR assessment policy; (2) Purpose; (3) Major changes in CCR assessment policy since the 2009-10 school year for financial reasons; (4) State financial support for students to take the CCR…

  17. Profile of State College and Career Readiness Assessments (CCR) Policy. South Carolina

    Science.gov (United States)

    Center on Education Policy, 2011

    2011-01-01

    This individual profile provides information on South Carolina's college and career readiness assessment policy. Some of the categories presented include: (1) CCR assessment policy; (2) Purpose; (3) Major changes in CCR assessment policy since the 2009-10 school year for financial reasons; (4) State financial support for students to take the CCR…

  18. Profile of State College and Career Readiness Assessments (CCR) Policy. Kentucky

    Science.gov (United States)

    Center on Education Policy, 2011

    2011-01-01

    This individual profile provides information on Kentucky's college and career readiness assessment policy. Some of the categories presented include: (1) CCR assessment policy; (2) Purpose; (3) Major changes in CCR assessment policy since the 2009-10 school year for financial reasons; (4) State financial support for students to take the CCR…

  19. Profile of State College and Career Readiness Assessments (CCR) Policy. Georgia

    Science.gov (United States)

    Center on Education Policy, 2011

    2011-01-01

    This individual profile provides information on Georgia's college and career readiness assessment policy. Some of the categories presented include: (1) CCR assessment policy; (2) Purpose; (3) Major changes in CCR assessment policy since the 2009-10 school year for financial reasons; (4) State financial support for students to take the CCR…

  20. Profile of State College and Career Readiness Assessments (CCR) Policy. North Dakota

    Science.gov (United States)

    Center on Education Policy, 2011

    2011-01-01

    This individual profile provides information on North Dakota's college and career readiness assessment policy. Some of the categories presented include: (1) CCR assessment policy; (2) Purpose; (3) Major changes in CCR assessment policy since the 2009-10 school year for financial reasons; (4) State financial support for students to take the CCR…

  1. Profile of State College and Career Readiness Assessments (CCR) Policy. Alabama

    Science.gov (United States)

    Center on Education Policy, 2011

    2011-01-01

    This individual profile provides information on Alabama's college and career readiness assessment policy. Some of the categories presented include: (1) CCR assessment policy; (2) Purpose; (3) Major changes in CCR assessment policy since the 2009-10 school year for financial reasons; (4) State financial support for students to take the CCR…

  2. Profile of State College and Career Readiness Assessments (CCR) Policy. New Mexico

    Science.gov (United States)

    Center on Education Policy, 2011

    2011-01-01

    This individual profile provides information on New Mexico's college and career readiness assessment policy. Some of the categories presented include: (1) CCR assessment policy; (2) Purpose; (3) Major changes in CCR assessment policy since the 2009-10 school year for financial reasons; (4) State financial support for students to take the CCR…

  3. Profile of State College and Career Readiness Assessments (CCR) Policy. Tennessee

    Science.gov (United States)

    Center on Education Policy, 2011

    2011-01-01

    This individual profile provides information on Tennessee's college and career readiness assessment policy. Some of the categories presented include: (1) CCR assessment policy; (2) Purpose; (3) Major changes in CCR assessment policy since the 2009-10 school year for financial reasons; (4) State financial support for students to take the CCR…

  4. Profile of State College and Career Readiness Assessments (CCR) Policy. California

    Science.gov (United States)

    Center on Education Policy, 2011

    2011-01-01

    This individual profile provides information on California's college and career readiness assessment policy. Some of the categories presented include: (1) CCR assessment policy; (2) Purpose; (3) Major changes in CCR assessment policy since the 2009-10 school year for financial reasons; (4) State financial support for students to take the CCR…

  5. Profile of State College and Career Readiness Assessments (CCR) Policy. West Virginia

    Science.gov (United States)

    Center on Education Policy, 2011

    2011-01-01

    This individual profile provides information on West Virginia's college and career readiness assessment policy. Some of the categories presented include: (1) CCR assessment policy; (2) Purpose; (3) Major changes in CCR assessment policy since the 2009-10 school year for financial reasons; (4) State financial support for students to take the CCR…

  6. Implication of Ccr4-Not complex function in mRNA quality control in Saccharomyces cerevisiae

    DEFF Research Database (Denmark)

    Assenholt, Jannie; Mouaikel, John; Saguez, Cyril

    2011-01-01

    RNPs are exported to the cytoplasm. The Ccr4-Not complex, which constitutes the major S. cerevisiae cytoplasmic deadenylase, has recently been implied in nuclear exosome–related processes. Consistent with a possible nuclear function of the complex, the deletion or mutation of Ccr4-Not factors also elicits...

  7. The Effects of the Recombinant CCR5 T4 Lysozyme Fusion Protein on HIV-1 Infection.

    Directory of Open Access Journals (Sweden)

    Qingwen Jin

    Full Text Available Insertion of T4 lysozyme (T4L into the GPCR successfully enhanced GPCR protein stability and solubilization. However, the biological functions of the recombinant GPCR protein have not been analyzed.We engineered the CCR5-T4L mutant and expressed and purified the soluble recombinant protein using an E.coli expression system. The antiviral effects of this recombinant protein in THP-1 cell lines, primary human macrophages, and PBMCs from different donors were investigated. We also explored the possible mechanisms underlying the observed antiviral effects.Our data showed the biphasic inhibitory and promotion effects of different concentrations of soluble recombinant CCR5-T4L protein on R5 tropic human immunodeficiency virus-1 (HIV-1 infection in THP-1 cell lines, human macrophages, and PBMCs from clinical isolates. We demonstrated that soluble recombinant CCR5-T4L acts as a HIV-1 co-receptor, interacts with wild type CCR5, down-regulates the surface CCR5 expression in human macrophages, and interacts with CCL5 to inhibit macrophage migration. Using binding assays, we further determined that recombinant CCR5-T4L and [125I]-CCL5 compete for the same binding site on wild type CCR5.Our results suggest that recombinant CCR5-T4L protein marginally promotes HIV-1 infection at low concentrations and markedly inhibits infection at higher concentrations. This recombinant protein may be helpful in the future development of anti-HIV-1 therapeutic agents.

  8. Limited protective effect of the CCR5Δ32/CCR5Δ32 genotype on human immunodeficiency virus infection incidence in a cohort of patients with hemophilia and selection for genotypic X4 virus

    DEFF Research Database (Denmark)

    Iversen, Astrid K. N.; Christiansen, Claus Bohn; Attermann, Jørn

    2003-01-01

    The relationship among CCR5 genotype, cytomegalovirus infection, and disease progression and death was studied among 159 human immunodeficiency virus (HIV)–infected patients with hemophilia. One patient (0.6%) had the CCR5Δ32/CCR5Δ32 genotype (which occurs in ∼2% of the Scandinavian population...

  9. Elucidation of the CCR1- and CCR5-binding modes of MIP-1α by application of an NMR spectra reconstruction method to the transferred cross-saturation experiments

    Energy Technology Data Exchange (ETDEWEB)

    Yoshiura, Chie; Ueda, Takumi; Kofuku, Yutaka; Matsumoto, Masahiko; Okude, Junya; Kondo, Keita; Shiraishi, Yutaro; Shimada, Ichio, E-mail: shimada@iw-nmr.f.u-tokyo.ac.jp [The University of Tokyo, Graduate School of Pharmaceutical Sciences (Japan)

    2015-12-15

    C–C chemokine receptor 1 (CCR1) and CCR5 are involved in various inflammation and immune responses, and regulate the progression of the autoimmune diseases differently. However, the number of residues identified at the binding interface was not sufficient to clarify the differences in the CCR1- and CCR5-binding modes to MIP-1α, because the NMR measurement time for CCR1 and CCR5 samples was limited to 24 h, due to their low stability. Here we applied a recently developed NMR spectra reconstruction method, Conservation of experimental data in ANAlysis of FOuRier, to the amide-directed transferred cross-saturation experiments of chemokine receptors, CCR1 and CCR5, embedded in lipid bilayers of the reconstituted high density lipoprotein, and MIP-1α. Our experiments revealed that the residues on the N-loop and β-sheets of MIP-1α are close to both CCR1 and CCR5, and those in the C-terminal helix region are close to CCR5. These results suggest that the genetic influence of the single nucleotide polymorphisms of MIP-1α that accompany substitution of residues in the C-terminal helix region, E57 and V63, would provide clues toward elucidating how the CCR5–MIP-1α interaction affects the progress of autoimmune diseases.

  10. Enriquecimento com calda do CCR para face de barragens

    Directory of Open Access Journals (Sweden)

    A. P. Wendler

    Full Text Available A construção de barragens de CCR prioriza a minimização de interferências, como a execução da face de montante, para garantia da produtividade. O estudo procurou avaliar as propriedades físicas do CCR enriquecido com calda, em substituição ao concreto convencional usualmente empregado na face, utilizando os mesmos materiais, central de concreto, mão de obra e equipamentos, empregados na construção da Usina Hidrelétrica Mauá. Para tanto foram feitos prismas experimentais de campo (com diferentes relações água/cimento e quantidades de calda e posterior extração de testemunhos, os quais foram submetidos a ensaios mecânicos e de permeabilidade. Os resultados mostraram que para relações água/cimento 0,74, o material resultante atendeu às especificações de projeto, para consumos de cimento notadamente menores (entre 70 e 85% do CCV.

  11. Frequency of CCR5delta32 in Brazilian populations

    Directory of Open Access Journals (Sweden)

    A.E. Vargas

    2006-03-01

    Full Text Available A sample of 103 randomly chosen healthy individuals from Alegrete, RS, Brazil, was tested for the CCR5delta32 allele, which is known to influence susceptibility to HIV-1 infection. The CCR5delta32 allele was identified by PCR amplification using specific primers flanking the region of deletion, followed by electrophoresis on a 3% agarose gel. The data obtained were compared to those reported for other populations and interpreted in terms of Brazilian history. The individuals studied came from a highly admixed population. Most of them were identified as white (N = 59, while blacks and browns (mulattoes were N = 13 and N = 31, respectively. The observed frequencies, considering the white, black and brown samples (6.8, 3.8, and 6.4%, respectively, suggest an important European parental contribution, even in populations identified as black and brown. However, in Brazil as a whole, this allele shows gradients indicating a relatively good correlation with the classification based on skin color and other physical traits, used here to define major Brazilian population groups.

  12. Preparation for and building of V-1 nuclear power plant

    International Nuclear Information System (INIS)

    Smatlak, S.; Spirko, M.

    1981-01-01

    Some findings and problems encountered during the construction of the V-1 nuclear power plant at Jaslovske Bohunice are discussed from the point of view of the investor, mainly problems associated with project preparation and relations between suppliers and the customer. The progress of construction is described and the dates are shown of the main stages of construction and tests. The construction proceeded according to a net diagram and was controlled by the construction management and a coordination group headed by the investor. An international start-up commission was established for the start-up stage. The fields are outlined of the participation and co-operation of Soviet organizations during project preparation, supplies, assembly, start-up, and fuel supplies for the V-1 nuclear power plant. (B.S.)

  13. Termination of exploitation of V 1 NPP - BIDSF projects

    International Nuclear Information System (INIS)

    Pnackova, L.

    2004-01-01

    In this paper the interview with engineer Peter Hlbocky, director of division of the Project of decommissioning of V 1 Nuclear Power Plant in Jaslovske Bohunice is presented. Project Manager Unit (PMU) was formed on the basis of directive of the General Director of the Slovenske elektrarne, a.s. The Director of the Division of decommissioning of the V 1 NPP and at the same time the Main manager of the PMU is engineer Peter Hlbocky. On this project participate 19 employees of the Slovenske elektrarne, a. s. (SE), 6 abroad employees of the consortium IBERINCO, 15 employees of the VUEZ and 25 abroad employees on the detached place of work in the Spain and France

  14. Backfitting of the nuclear plant V1 power control system

    International Nuclear Information System (INIS)

    Karpeta, C.; Rubek, J.; Stirsky, P.

    1985-01-01

    The paper deals with some aspects of implementation of modifications into the Czechoslovak nuclear plant V1 control system as called for on the basis of experience gained during the first period of the plant operation. Brief description of the plant power control system and its main functions is given. Some deficiencies in the system performance during abnormal conditions are outlined and measures taken to overcome them are presented. (author)

  15. The graphical user interface for CRISTAL V1

    International Nuclear Information System (INIS)

    Heulers, L.; Courtois, G.; Fernex, F.; Gomit, J.M.; Letang, E.

    2003-01-01

    This paper deals with the new Graphical User Interface (GUI) of the CRISTAL V1 package devoted to criticality studies including burn up calculations. The aim of this GUI is to offer users a high level of user-friendliness and flexibility in the data description and the results analysis of codes of the package. The three main components of the GUI (CIGAIES, EJM and OPOSSUM) are presented. The different functionalities of the tools are explained through some applications. (author)

  16. CRISTAL V1: Criticality package for burn up credit calculations

    International Nuclear Information System (INIS)

    Gomit, Jean-Michel; Cousinou, Patrick; Gantenbein, Francoise; Diop, Cheikh; Fernandez de Grado, Guy; Mijuin, Dominique; Grouiller, Jean-Paul; Marc, Andre; Toubon, Herve

    2003-01-01

    The first version of the CRISTAL package, created and validated as part of a joint project between IRSN, COGEMA and CEA, was delivered to users in November 1999. This fruitful cooperation between IRSN, COGEMA and CEA has been pursued until 2003 with the development and the validation of the package CRISTAL V1, whose main objectives are to improve the criticality safety studies including the Burn up Credit effect. (author)

  17. The Bohunice NPP V-1 units nuclear safety upgrading

    International Nuclear Information System (INIS)

    Mlcuch, M.

    2000-01-01

    Safety upgrading and operational reliability improvement was carried out by the Bohunice NPP V-1 staff continuously since the plant commissioning. By now, more than 1200 minor or major modifications have been implemented, either by the NPP maintenance staff or by the contractors. Based on findings of safety assessment missions invited by Bohunice NPP in 1990 - 1991, the Czecho-slovak Nuclear Regulatory Authority (CSKAE) issued the decision No. 5/91 of 81 safety upgrading measures to be taken in different areas. These improvements are referred to as the 'Small Reconstruction of the Bohunice V-1 NPP'. Realization of measures during Small reconstruction of the Bohunice NPP V-1 became a power plant, which further operation is acceptable from safety point of view, but it is also necessary further safety improvement. During the period of the Small Reconstruction the development of a Safety Report for the Gradual reconstruction has been completed. Based on this report the SR Nuclear Regulatory Authority issued the Decision No. 1/94, in which requires 59 upgrading measures in different areas to be addressed. The development of Basic Engineering of the Gradual Reconstruction has been contracted to the Siemens AG. Implementation of safety measures are provided through contract with the consortium REKON (which consists of Siemens AG company and Nuclear Power Plants Research Institute Trnava) and other Czech, Russian and Slovak companies. The Gradual Reconstruction of Bohunice NPP V-1 will be finished in 2000. By implementation of the measures carried out during Gradual Reconstruction achievement of an internationally acceptable nuclear safety level will be reached. (author)

  18. Assessment of ICARE/CATHARE V1 Severe Accident Code

    International Nuclear Information System (INIS)

    Chatelard, Patrick; Fleurot, Joelle; Marchand, Olivier; Drai, Patrick

    2006-01-01

    The ICARE/CATHARE code system has been developed by the French 'Institut de Radioprotection et de Surete Nucleaire' (IRSN) in the last decade for the detailed evaluation of Severe Accident (SA) consequences in a primary system. It is composed of the coupling of the core degradation IRSN code ICARE2 and of the thermal-hydraulics French code CATHARE2. It has been extensively used to support the level 2 Probabilistic Safety Assessment (PSA-2) of the 900 MWe PWR. This paper presents the synthesis of the ICARE/CATHARE V1 assessment which was conducted in the frame of the 'International ICARE/CATHARE Users' Club', under the management of IRSN. The ICARE/CATHARE V1 validation matrix is composed of more than 60 experiments, distributed in few thermal-hydraulics non-regression tests (to handle the front end phase of a severe accident), numerous Separate-Effect Tests, about 30 Integral Tests covering both the early and the late degradation phases, as well as a 'circuit' experiment including hydraulics loops. Finally, the simulation of the TMI-2 accident was also added to assess the code against real conditions. This validation task was aimed at assessing the ICARE/CATHARE V1 capabilities (including the stand-alone ICARE2 V3mod1 version) and also at proposing recommendations for an optimal use of this version ('Users' Guidelines'). Thus, with a correct account for the recommended guidelines, it appeared that the last ICARE/CATHARE V1 version could be reasonably used to perform best-estimate reactor studies up to a large corium slumping into the lower head. (authors)

  19. METEOR v1.0 - A usage example

    International Nuclear Information System (INIS)

    Palomo, E.

    1994-01-01

    This script describes a detailed example of the use of the software package METEOR for statistical analysis of meteorological data series. A real spanish meteorological data set is chosen to show the capabilities of METEOR. Output files and resultant plots provided of their interpretations are compiled in three appendixes. The original version of METEOR have been developed by Ph. D.Elena Palomo, CIEMAT-IER, GIASE. It is built by linking programs and routines written in FORTRAN 77 and it adds the graphical capabilities of GNUPLOT. The shape of this toolbox was designed following the criteria of modularity, flexibility and agility criteria. All the input, output and analysis options are structured in three main menus: i) the first is aimed to evaluate the quality of the data set; ii) the second is aimed for pre-processing of the data; and iii) the third is aimed towards the statistical analyses and for creating the graphical outputs. Actually the information about METEOR is constituted by three documents written is spanish: 1) METEOR v1.0: User's guide; 2) METEOR v1.0: A usage example; 3) METEOR v1 .0: Design and structure of the software package. (Author)

  20. MagPy: A Python toolbox for controlling Magstim transcranial magnetic stimulators.

    Science.gov (United States)

    McNair, Nicolas A

    2017-01-30

    To date, transcranial magnetic stimulation (TMS) studies manipulating stimulation parameters have largely used blocked paradigms. However, altering these parameters on a trial-by-trial basis in Magstim stimulators is complicated by the need to send regular (1Hz) commands to the stimulator. Additionally, effecting such control interferes with the ability to send TMS pulses or simultaneously present stimuli with high-temporal precision. This manuscript presents the MagPy toolbox, a Python software package that provides full control over Magstim stimulators via the serial port. It is able to maintain this control with no impact on concurrent processing, such as stimulus delivery. In addition, a specially-designed "QuickFire" serial cable is specified that allows MagPy to trigger TMS pulses with very low-latency. In a series of experimental simulations, MagPy was able to maintain uninterrupted remote control over the connected Magstim stimulator across all testing sessions. In addition, having MagPy enabled had no effect on stimulus timing - all stimuli were presented for precisely the duration specified. Finally, using the QuickFire cable, MagPy was able to elicit TMS pulses with sub-millisecond latencies. The MagPy toolbox allows for experiments that require manipulating stimulation parameters from trial to trial. Furthermore, it can achieve this in contexts that require tight control over timing, such as those seeking to combine TMS with fMRI or EEG. Together, the MagPy toolbox and QuickFire serial cable provide an effective means for controlling Magstim stimulators during experiments while ensuring high-precision timing. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. DMPD: Macrophage activation through CCR5- and CXCR4-mediated gp120-elicited signalingpathways. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 12960231 Macrophage activation through CCR5- and CXCR4-mediated gp120-elicited sign...82. Epub 2003 Jul 22. (.png) (.svg) (.html) (.csml) Show Macrophage activation through CCR5- and CXCR4-media...on through CCR5- and CXCR4-mediated gp120-elicited signalingpathways. Authors Lee C, Liu QH, Tomkowicz B, Yi

  2. Assessment of ICARE/CATHARE V1mod1 and V1 applications to full scale studies

    International Nuclear Information System (INIS)

    Chatelard, P.; Barre, F.; Mutelle, H.

    2001-01-01

    The objective initially assigned to the ICARE/CATHARE V1mod1 validation task was to draw a synthesis of the ability of the code to correctly reproduce the main physical processes occurring during severe accidents. Therefore, both the domain in which the ICARE/CATHARE V1mod1 predictions are satisfactory (good confidence level) and, conversely, the identification of the main code deficiencies have to be highlighted. After a brief recall of the validation strategy and the current status of the work, this paper summarizes the main lessons which were drawn by IPSN from the validation activity which was conducted during the last two years (in 2000-2001) in the particular framework of the Users' Club (both IPSN and several foreign partners were involved in this task, under the management of IPSN). (authors)

  3. Association of TGFβ1, TNFα, CCR2 and CCR5 gene polymorphisms in type-2 diabetes and renal insufficiency among Asian Indians

    Directory of Open Access Journals (Sweden)

    Gupta Arvind

    2007-04-01

    Full Text Available Abstract Background Cytokines play an important role in the development of diabetic chronic renal insufficiency (CRI. Transforming growth factor β1 (TGF β1 induces renal hypertrophy and fibrosis, and cytokines like tumor necrosis factor-alpha (TNFα, chemoattractant protein-1 (MCP-1, and regulated upon activation and normal T cell expressed and secreted (RANTES mediate macrophage infiltration into kidney. Over expression of these chemokines leads to glomerulosclerosis and interstitial fibrosis. The effect of MCP-1 and RANTES on kidney is conferred by their receptors i.e., chemokine receptor (CCR-2 and CCR-5 respectively. We tested association of nine single nucleotide polymorphisms (SNPs from TGFβ1, TNFα, CCR2 and CCR5 genes among individuals with type-2 diabetes with and without renal insufficiency. Methods Type-2 diabetes subjects with chronic renal insufficiency (serum creatinine ≥ 3.0 mg/dl constituted the cases, and matched individuals with diabetes of duration ≥ 10 years and normoalbuminuria were evaluated as controls from four centres in India. Allelic and genotypic contributions of nine SNPs from TGFβ1, TNFα, CCR2 and CCR5 genes to diabetic CRI were tested by computing odds ratio (OR and 95% confidence intervals (CI. Sub-analysis of CRI cases diabetic retinopathy status as dependent variable and SNP genotypes as independent variable in a univariate logistic regression was also performed. Results SNPs Tyr81His and Thr263Ile in TGF β1 gene were monomorphic, and Arg25Pro in TGF β1 gene and Δ32 polymorphism in CCR5 gene were minor variants (minor allele frequency A SNP of CCR5 gene has been observed and the allele 59029A seems to confer predisposition to development of diabetic CRI (OR 1.39; CI 1.04–1.84. In CRI subjects a compound group of genotypes "GA and AA" of SNP G>A -800 was found to confer predisposition for proliferative retinopathy (OR 3.03; CI 1.08–8.50, p = 0.035. Conclusion Of the various cytokine gene

  4. METEOR v1.0 - A usage example; METEOR v1.0 - Un ejemplo de uso

    Energy Technology Data Exchange (ETDEWEB)

    Palomo, E.

    1994-07-01

    This script describes a detailed example of the use of the software package METEOR for statistical analysis of meteorological data series. A real spanish meteorological data set is chosen to show the capabilities of METEOR. Output files and resultant plots provided of their interpretations are compiled in three appendixes. The original version of METEOR have been developed by Ph. D.Elena Palomo, CIEMAT-IER, GIASE. It is built by linking programs and routines written in FORTRAN 77 and it adds the graphical capabilities of GNUPLOT. The shape of this toolbox was designed following the criteria of modularity, flexibility and agility criteria. All the input, output and analysis options are structured in three main menus: i) the first is aimed to evaluate the quality of the data set; ii) the second is aimed for pre-processing of the data; and iii) the third is aimed towards the statistical analyses and for creating the graphical outputs. Actually the information about METEOR is constituted by three documents written is spanish: 1) METEOR v1.0: User's guide; 2) METEOR v1.0: A usage example; 3) METEOR v1 .0: Design and structure of the software package. (Author)

  5. METEOR v1.0 - User's Guide; METEOR v1.0 - Guia de Usuarios

    Energy Technology Data Exchange (ETDEWEB)

    Palomo, E.

    1994-07-01

    This script is a User's Guide for the software package METEOR for statistical analysis of meteorological data series. The original version of METEOR have been developed by Ph.D. Elena Palomo, CIEMAT-IER, GIMASE. It is built by linking programs and routines written in FORTRAN 77 and it adds the graphical capabilities of GNUPLOT. The shape of this toolbox was designed following the criteria of modularity, flexibility and agility criteria. All the input, output and analysis options are structured in three main menus: i) the first is aimed to evaluate the quality of the data set; ii) the second is aimed for pre-processing of the data; and iii) the third is aimed towards the statistical analyses and for creating the graphical outputs. Actually the information about METEOR is constituted by three documents written in spanish: 1) METEOR v1.0: User's guide; 2) METEOR v1.0: A usage example; 3) METEOR v1.0: Design and structure of the software package. (Author)

  6. Preparation and evaluation of freeze-dried Mag3 kits for 99m Tc-labelling

    International Nuclear Information System (INIS)

    El-Mohty, A.A.; El-Ghany, E.A.; El-Kolaly, M.T.; Raieh, M.; EL-Bary, A.A.

    1996-01-01

    The freeze-dried Mag 3 kits were designed for both ligand trans chelation and direct labelling techniques. The solution of Sn-Mag 3 was sterilized by 0.22 μU mill pore filtration and dispensed in a laminar flow hood (1 m I / vial) then, the vials were introduced to the lyophilized. The process of lyophilization was continued for 24 hours. At end of the cycle, the vials were closed under nitrogen. The moisture content of the freeze-dried Mag 3 kits was determined and it was found equal to 0.1% also, the losses of tin (II) during the freeze-drying cycle did not exceed 5%. It was found that the Mag 3 freeze-dried kits were sterile, pyrogen free and does not have any unexpected toxicity. The prepared Mag 3 freeze-dried kits have high radiochemical purity > 97% and high stability for more than 8 h after labelling. The biodistribution shows rapid renal excretion at 15 min post injection. 3 figs., 4 tabs

  7. Magnetically separable polymer (Mag-MIP) for selective analysis of biotin in food samples.

    Science.gov (United States)

    Uzuriaga-Sánchez, Rosario Josefina; Khan, Sabir; Wong, Ademar; Picasso, Gino; Pividori, Maria Isabel; Sotomayor, Maria Del Pilar Taboada

    2016-01-01

    This work presents an efficient method for the preparation of magnetic nanoparticles modified with molecularly imprinted polymers (Mag-MIP) through core-shell method for the determination of biotin in milk food samples. The functional monomer acrylic acid was selected from molecular modeling, EGDMA was used as cross-linking monomer and AIBN as radical initiator. The Mag-MIP and Mag-NIP were characterized by FTIR, magnetic hysteresis, XRD, SEM and N2-sorption measurements. The capacity of Mag-MIP for biotin adsorption, its kinetics and selectivity were studied in detail. The adsorption data was well described by Freundlich isotherm model with adsorption equilibrium constant (KF) of 1.46 mL g(-1). The selectivity experiments revealed that prepared Mag-MIP had higher selectivity toward biotin compared to other molecules with different chemical structure. The material was successfully applied for the determination of biotin in diverse milk samples using HPLC for quantification of the analyte, obtaining the mean value of 87.4% recovery. Copyright © 2015 Elsevier Ltd. All rights reserved.

  8. Expression pattern of Ccr2 and Cx3cr1 in inherited retinal degeneration.

    Science.gov (United States)

    Kohno, Hideo; Koso, Hideto; Okano, Kiichiro; Sundermeier, Thomas R; Saito, Saburo; Watanabe, Sumiko; Tsuneoka, Hiroshi; Sakai, Tsutomu

    2015-10-12

    Though accumulating evidence suggests that microglia, resident macrophages in the retina, and bone marrow-derived macrophages can cause retinal inflammation which accelerates photoreceptor cell death, the details of how these cells are activated during retinal degeneration (RD) remain uncertain. Therefore, it is important to clarify which cells play a dominant role in fueling retinal inflammation. However, distinguishing between microglia and macrophages is difficult using conventional techniques such as cell markers (e.g., Iba-1). Recently, two mouse models for visualizing chemokine receptors were established, Cx3cr1 (GFP/GFP) and Ccr2 (RFP/RFP) mice. As Cx3cr1 is expressed in microglia and Ccr2 is reportedly expressed in activated macrophages, these mice have the potential to distinguish microglia and macrophages, yielding novel information about the activation of these inflammatory cells and their individual roles in retinal inflammation. In this study, c-mer proto-oncogene tyrosine kinase (Mertk) (-/-) mice, which show photoreceptor cell death due to defective retinal pigment epithelium phagocytosis, were employed as an animal model of RD. Mertk (-/-) Cx3cr1 (GFP/+) Ccr2 (RFP/+) mice were established by breeding Mertk (-/-) , Cx3cr1 (GFP/GFP) , and Ccr2 (RFP/RFP) mice. The retinal morphology and pattern of inflammatory cell activation and invasion of Mertk (-/-) Cx3cr1 (GFP/+) Ccr2 (RFP/+) mice were evaluated using retina and retinal pigment epithelium (RPE) flat mounts, retinal sections, and flow cytometry. Four-week-old Mertk (-/-) Cx3cr1 (GFP/+) Ccr2 (RFP/+) mice showed Cx3cr1-GFP-positive microglia in the inner retina. Cx3cr1-GFP and Ccr2-RFP dual positive activated microglia were observed in the outer retina and subretinal space of 6- and 8-week-old animals. Ccr2-RFP single positive bone marrow-derived macrophages were observed to migrate into the retina of Mertk (-/-) Cx3cr1 (GFP/+) Ccr2 (RFP/+) mice. These invading cells were still observed in the

  9. Homoeologous Recombination of the V1r1-V1r2 Gene Cluster of Pheromone Receptors in an Allotetraploid Lineage of Teleosts

    Directory of Open Access Journals (Sweden)

    Lei Zhong

    2017-11-01

    Full Text Available In contrast to other olfactory receptor families that exhibit frequent lineage-specific expansions, the vomeronasal type 1 receptor (V1R family exhibits a canonical six-member repertoire in teleosts. V1r1 and V1r2 are present in no more than one copy in all examined teleosts, including salmons, which are ancient polyploids, implying strict evolutionary constraints. However, recent polyploids have not been examined. Here, we identified a young allotetraploid lineage of weatherfishes and investigated their V1r1-V1r2 cluster. We found a novel pattern that the parental V1r1-V1r2 clusters had recombined in the tetraploid genome and that the recombinant was nearly fixed in the tetraploid population. Subsequent analyses suggested strong selective pressure, for both a new combination of paralogs and homogeneity among gene duplicates, acting on the V1r1-V1r2 pair.

  10. Seismic re-evaluation criteria for Bohunice V1 reconstruction

    International Nuclear Information System (INIS)

    Campbell, R.; Schlund, H.; Warnken, L.

    2001-01-01

    Bohunice V1 in Slovakia is a Russian designed two unit WWER 440, Model 230 Pressurized Water Reactor. The plant was not originally designed for earthquake. Subsequent and ongoing reassessments now confirm that the seismic hazard at the site is significant. EBO, the plant owner has contracted with a consortium lead by Siemens AG (REKON) to do major reconstruction of the plant to significantly enhance its safety systems by the addition of new systems and the upgrading of existing systems. As part of the reconstruction, a complete seismic assessment and upgrading is required for existing safety relevant structures, systems and components. It is not practical to conduct this reassessment and upgrading using criteria applied to new design of nuclear power plants. Alternate criteria may be used to achieve adequate safety goals. Utilities in the U.S. have faced several seismic issues with operating NPPs and to resolve these issues, alternate criteria have been developed which are much more cost effective than use of criteria for new design. These alternate criteria incorporate the knowledge obtained from investigation of the performance of equipment in major earthquakes and include provisions for structures and passive equipment to deform beyond the yield point, yet still provide their essential function. IAEA has incorporated features of these alternate criteria into draft Technical Guidelines for application to Bohunice V1 and V2. REKON has developed plant specific criteria and procedures for the Bohunice V1 reconstruction that incorporate major features of the U.S. developed alternate criteria, comply to local codes and which envelop the draft IAEA Technical Guidelines. Included in these criteria and procedures are comprehensive walkdown screening criteria for equipment, piping, HVAC and cable raceways, analytical criteria which include inelastic energy absorption factors defined on an element basis and testing criteria which include specific guidance on interpretation

  11. Bohunice V-1. Review of safety upgrading and operating experiences

    International Nuclear Information System (INIS)

    Korec, J.; Kuschel, D.

    2000-01-01

    The Bohunice site in the Slovak Republic has two Russian-designed twin-unit nuclear power plants, one equipped with reactors of the WWER 440/230 type, the other with type WWER 440/213 reactors. Two older units (V-1) started commercial operation in late 1978 and 1980 respectively and have been supplying electricity to the national grid since that time without any events that could have degraded plant safety level. In the period prior to 1990 the utility Slovenske Elektrarne (S.E.) performed extensive modifications and upgrades to the original design of the two older units V-1 NPP. Furthermore, significant steps in safety improvement for Bohunice NPP V-1 have been made since 1990. Following the political restructuring of the former Czechoslovakia and the country's new open-door policy towards western organizations, several international expert missions were focused on evaluation of Bohunice NPP safety status level and operational reliability, particularly targeting the two older units. Based on recommendations of individual expert missions and complementary deterministic and probabilistic safety analyses performed by S.E., the Czechoslovak Nuclear Regulatory Authority issued the Resolution No. 5/91 defining 81 measures concerning further safety and reliability improvement of Bohunice V1 .A range of short-term and long-term upgrades was prioritised in terms of importance to plant safety and work to implement these measures commenced in the early nineties. During the 'Small Reconstruction' from 1991 to 1993 some of the short term upgrading measures were realized to eliminate the most serious safety deficits, thus to achieve a significant reduction in core damage frequency and a major improvement in confinement integrity. In this paper and presentation the goals of the gradual reconstruction project, basic engineering, detailed engineering and realization, last major stage of Unit 2 upgrade, as well as final stage of Unit 1 upgrade in early 2000 are presented

  12. Radiation supervision - NPPs A-1, V-1, V-2

    International Nuclear Information System (INIS)

    2000-01-01

    In this leaflet the radiation supervision of the nuclear power plants A-1, V-1, V-2 is presented. Off-site radiation supervision laboratory is a part of monitoring scheme of the NPPs. More than 1150 samples are taken from the environment annually. The tele-dosimetric system was constructed to improve the quality of the Bohunice NPPs operation impacts supervision. It has been running in a continuous operation from 1992 and providing supervision of the nuclear power plant off-site area within 25 kilometres. The tele-dosimetric system is described

  13. An Autopsy Case of Amyotrophic Lateral Sclerosis with Waldenström Macroglobulinemia and Anti-MAG Gammopathy

    Directory of Open Access Journals (Sweden)

    Snejana Jurici

    2011-12-01

    Full Text Available We report the case of a 71-year-old woman with typical signs of bulbar amyotrophic lateral sclerosis (ALS associated with immunoglobulin M (IgM monoclonal gammopathy and anti-MAG (myelin-associated glycoprotein antibodies. This unusual association between ALS and anti-MAG antibodies has previously been reported in a single case. Our present case, at neuropathological examination, demonstrated no causative link between anti-MAG antibodies and ALS.

  14. Interaction of small molecule inhibitors of HIV-1 entry with CCR5

    International Nuclear Information System (INIS)

    Seibert, Christoph; Ying Weiwen; Gavrilov, Svetlana; Tsamis, Fotini; Kuhmann, Shawn E.; Palani, Anandan; Tagat, Jayaram R.; Clader, John W.; McCombie, Stuart W.; Baroudy, Bahige M.; Smith, Steven O.; Dragic, Tatjana; Moore, John P.; Sakmar, Thomas P.

    2006-01-01

    The CC-chemokine receptor 5 (CCR5) is the major coreceptor for macrophage-tropic (R5) HIV-1 strains. Several small molecule inhibitors of CCR5 that block chemokine binding and HIV-1 entry are being evaluated as drug candidates. Here we define how CCR5 antagonists TAK-779, AD101 (SCH-350581) and SCH-C (SCH-351125), which inhibit HIV-1 entry, interact with CCR5. Using a mutagenesis approach in combination with a viral entry assay to provide a direct functional read out, we tested predictions based on a homology model of CCR5 and analyzed the functions of more than 30 amino acid residues. We find that a key set of aromatic and aliphatic residues serves as a hydrophobic core for the ligand binding pocket, while E283 is critical for high affinity interaction, most likely by acting as the counterion for a positively charged nitrogen atom common to all three inhibitors. These results provide a structural basis for understanding how specific antagonists interact with CCR5, and may be useful for the rational design of new, improved CCR5 ligands

  15. Quantum continual measurements and a posteriori collapse on CCR

    International Nuclear Information System (INIS)

    Belavkin, V.P.

    1992-01-01

    A quantum stochastic model for the Markovian dynamics of an open system under the nondemolition unsharp observation which is continuous in time, is given. A stochastic equation for the posterior evolution of a quantum continuously observed system is derived and the spontaneous collapse (stochastically continuous reduction of the wave packet) is described. The quantum Langevin evolution equation is solved for the case of a quasi-free Hamiltonian in the initial CCR algebra with a linear output channel, and the posterior dynamics corresponding to an initial Gaussian state is found. It is shown for an example of the posterior dynamics of a quantum oscillator that any mixed state under a complete nondemolition measurement collapses exponentially to a pure Gaussian one. (orig.)

  16. MAG3 renal scintigraphy: improved ability to make anatomical diagnoses in neonates

    International Nuclear Information System (INIS)

    Rossleigg, M.A.; Kainer, G.; Rosenberg, A.R.; Farnaworth, R.H.

    1995-01-01

    Technetium-99m mercaptoacetyltriglycine (MAG3) is the most recently introduced renal radiopharmaceutical in Australia and is established as the agent of choice for use in diuresis renography, particularly in neonates and infants. It provides superior anatomical information compared to previously used agents. Three cases are reported in which MAG3 diuresis renography was performed in neonates, who were found to have hydronephrosis detected antenatally. In two neonates, a previously unrecognized horseshoe kidney was demonstrated and in case 3 there were scan features characteristic of a ureterocele. It is highly unlikely that these abnormalities would have been delineated with 99m Tc dimethyltriamine pentaacetic acid (DTPA) study, as confirmed in case 1, because of the relatively poor uptake of DTPA when compared to MAG3. 6 refs., 3 figs

  17. Modeling of welded bead profile for rapid prototyping by robotic MAG welding

    Institute of Scientific and Technical Information of China (English)

    CAO Yong; ZHU Sheng; WANG Tao; WANG Wanglong

    2009-01-01

    As a deposition technology, robotic metal active gas(MAG) welding has shown new promise for rapid prototyping (RP) of metallic parts. During the process of metal forming using robotic MAG welding, sectional profile of single-pass welded bead is critical to formed accuracy and quality of metal pans. In this paper, the experiments of single-pass welded bead for rapid prototyping using robotic MAG welding were carried out. The effect of some edge detectors on the cross-sectional edge of welded bead was discussed and curve fitting was applied using leat square fitting. Consequently, the mathematical model of welded bead profile was developed. The experimental results show that good shape could be obtained under suitable welding parameters. Canny operawr is suitable to edge detection of welded bead profile, and the mathematical model of welded bead profile developed is approximately parabola.

  18. Acute neurological worsening after Rituximab treatment in patients with anti-MAG neuropathy.

    Science.gov (United States)

    Sala, Emilie; Robert-Varvat, Florence; Paul, Stéphane; Camdessanché, Jean-Philippe; Antoine, Jean-Christophe

    2014-10-15

    Patients with peripheral neuropathy and anti-MAG monoclonal IgM may respond to Rituximab, a humanized monoclonal anti-CD20 antibody. We report on three patients with peripheral neuropathy and anti-MAG monoclonal IgM who deteriorated under Rituximab and reviewed seven previously published cases. Worsening was acute and severe, and occurred during the treatment period. All the patients improved after deterioration but at final evaluation only one was improved comparatively to baseline, five were worsened and four were stabilized. Deterioration was not clearly associated with an increase of the anti-MAG antibody titer. Two patients received Rituximab prior or after the course which induced worsening without adverse reaction. Although rare, acute worsening of the neuropathy can occur after Rituximab. The deterioration is however reversible within some weeks to several months. Copyright © 2014 Elsevier B.V. All rights reserved.

  19. Chemical and biological studies on the technetium/S-unprotected MAG3-system

    International Nuclear Information System (INIS)

    Johannsen, B.; Noll, B.; Heise, K.H.; May, K.; Syhre, R.; Reiss, H.; Strangfeld, D.; Bruch, L.; Modersohn, D.

    1990-01-01

    Labelling studies performed with S-unprotected mercaptoacetylglycylglycine (MAG 3 ) have shown that various products of different biological properties exist in the Tc-MAG 3 system. Besides the known Tc(V)oxo complex recently introduced into nuclear medicine for renal function diagnosis, mainly three species were characterized by HPLC, TLC, electrophoresis and UV-VIS spectroscopy as well as biodistribution studies in rats and minipigs. Alteration of preparation conditions, both at carrier level (10 -4 M) and with no-carrier-added 99m Tc such as concentrations, sequence of reactants, pH, and time enabled to elucidate reaction routes within the system, interdependency of the Tc species, and vulnerability of the kidney imaging agent. The renal function agent was prepared by reduction of pertechnetate by stannous tartrate in solution of S-unprotected MAG 3 at pH > 11, and subsequent neutralization. (author)

  20. CCR8 signaling influences Toll-like receptor 4 responses in human macrophages in inflammatory diseases.

    Science.gov (United States)

    Reimer, Martina Kvist; Brange, Charlotte; Rosendahl, Alexander

    2011-12-01

    CCR8 immunity is generally associated with Th2 responses in allergic diseases. In this study, we demonstrate for the first time a pronounced attenuated influx of macrophages in ovalbumin (OVA)-challenged CCR8 knockout mice. To explore whether macrophages in human inflamed lung tissue also were CCR8 positive, human lung tissue from patients with chronic obstructive pulmonary disease (COPD) was evaluated. Indeed, CCR8 expression was pronounced in invading monocytes/macrophages from lungs of patients with Global Initiative for Obstructive Lung Disease (GOLD) stage IV COPD. Given this expression pattern, the functional role of CCR8 on human macrophages was evaluated in vitro. Human peripheral blood monocytes expressed low levels of CCR8, while macrophage colony-stimulating factor (M-CSF)-derived human macrophages expressed significantly elevated surface levels of CCR8. Importantly, CCL1 directly regulated the expression of CD18 and CD49b and hence influenced the adhesion capacity of human macrophages. CCL1 drives chemotaxis in M-CSF-derived macrophages, and this could be completely inhibited by lipopolysaccharide (LPS). Whereas both CCL1 and LPS monotreatment inhibited spontaneous superoxide release in macrophages, CCL1 significantly induced superoxide release in the presence of LPS in a dose-dependent manner. Finally, CCL1 induced production of proinflammatory cytokines such as tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) and could inhibit LPS-induced cytokine production in a dose-dependent manner. Our data demonstrate, for the first time, the presence of CCR8 on inflammatory macrophages in human COPD lung tissue. Importantly, the functional data from human macrophages suggest a potential cross talk between the CCR8 and the Toll-like receptor 4 (TLR4) pathways, both of which are present in COPD patients.

  1. The CrowdMag App - turning your smartphone into a travelling magnetic observatory

    Science.gov (United States)

    Saltus, Richard; Nair, Manoj

    2017-04-01

    In 2014, we started the "CrowdMag" Project to collect vector magnetic data from digital magnetometers in smartphones. In October 2014, we released our first-generation Android and iOS apps. Currently, the CrowdMag Project has more than 15,000 enthusiastic users contributing more than 12 million magnetic data points from around the world. NOAA's National Centers for Environmental Information (NCEI), in partnership with the University of Colorado's Cooperative Institute for Research in the Environmental Sciences (CIRES) develops magnetic field models to aid navigation, resource exploration and scientific research. We use observatories, satellites and ship/airborne surveys to measure the magnetic data. However, the measurements leave gaps in coverage, particularly for short-wavelength urban noise. Our ultimate goal is to use data from the CrowdMag Project to improve global magnetic data coverage. Here we present some early results from the analysis of the crowdsourced magnetic data. A global magnetic model derived solely based on CrowdMag data is generally consistent with satellite-derived models such as World Magnetic Model. A unique contribution of the CrowdMag Project is the collection of ground level magnetic data in densely populated regions with an unprecedented spatial resolution. For example, we show a magnetic map (by binning the data collected into 100x100m cells) of central Boulder using 170,000 data points collected by about 60 devices over the duration October 2014- January 2016. The median magnetic field value is consistent with the expected magnitude of the Earth's background magnetic field. The standard deviation of the CrowdMag total field (F) values is much higher than the expected natural (i.e., diurnal and geologic) magnetic field variation. However, the phone's magnetometer is sensitive enough to capture the larger magnitude magnetic signature from the urban magnetic sources. We discuss the reliability of crowdsourced magnetic maps and their

  2. Preparation, radiochemical purity control and stability of 99mTc-mertiatide (Mag-3)

    International Nuclear Information System (INIS)

    Van Hemert, F.J.; Schimmel, K.J.M.; Van Eck-Smit, B.L.F.; Van Lenthe, H.

    2005-01-01

    Scintigraphic image analysis of 99m Tc-mertiatide (Mag-3, mercaptoacetyltriglycine) clearance provides the determination of the blood flow, the tubular transit time and the excretion as well from both kidneys. Radiopharmaceutical routine recommends a radiochemical purity control before administration of the product to a patient. The main objective of this study is to develop a Mag-3 labeling procedure that fits better than the previous one in our daily routine production of radiopharmaceuticals. Increasing proportions of 99m Tc-Mag-3 were measured during the heating and cooling steps of the Mag-3 labeling procedure. High performance liquid chromatography (HPLC) analysis was used to confirm the results of a rapid radiochemical quality control assay on standard instant thin-layer chromatography-silica gel (ITLC-SG) paper. The reconstitution time takes 20-25 minutes from the harvest of pertechnetate to a ready-for-use calibrated patient syringe. The HPLC profile of 99m Tc-Mag-3 including its minor impurities remains unchanged for 24-48 hours after reconstitution. The application of a programmable Peltier-directed device for heating/cooling provides a better control of the temperature course. The procedure proposed fully meets the labeling criteria recommended by the supplier and can be performed with a minimum of attention within a time-span that we formerly needed for solely the radiochemical purity control assay. Moreover, 99m Tc-Mag-3 prepared in this way seems to be considerably more stable than mentioned in the manufacturer's instructions. (author)

  3. Control of Both Myeloid Cell Infiltration and Angiogenesis by CCR1 Promotes Liver Cancer Metastasis Development in Mice

    Directory of Open Access Journals (Sweden)

    Mathieu Paul Rodero

    2013-06-01

    Full Text Available Expression of the CC chemokine receptor 1 (CCR1 by tumor cells has been associated with protumoral activity; however, its role in nontumoral cells during tumor development remains elusive. Here, we investigated the role of CCR1 deletion on stromal and hematopoietic cells in a liver metastasis tumor model. Metastasis development was strongly impaired in CCR1-deficient mice compared to control mice and was associated with reduced liver monocyte infiltration. To decipher the role of myeloid cells, sublethally irradiated mice were reconstituted with CCR1-deficient bone marrow (BM and showed better survival rates than the control reconstituted mice. These results point toward the involvement of CCR1 myeloid cell infiltration in the promotion of tumor burden. In addition, survival rates were extended in CCR1-deficient mice receiving either control or CCR1-deficient BM, indicating that host CCR1 expression on nonhematopoietic cells also supports tumor growth. Finally, we found defective tumor-induced neoangiogenesis (in vitro and in vivo in CCR1-deficient mice. Overall, our results indicate that CCR1 expression by both hematopoietic and nonhematopoietic cells favors tumor aggressiveness. We propose CCR1 as a potential therapeutical target for liver metastasis therapy.

  4. Attention and normalization circuits in macaque V1

    Science.gov (United States)

    Sanayei, M; Herrero, J L; Distler, C; Thiele, A

    2015-01-01

    Attention affects neuronal processing and improves behavioural performance. In extrastriate visual cortex these effects have been explained by normalization models, which assume that attention influences the circuit that mediates surround suppression. While normalization models have been able to explain attentional effects, their validity has rarely been tested against alternative models. Here we investigate how attention and surround/mask stimuli affect neuronal firing rates and orientation tuning in macaque V1. Surround/mask stimuli provide an estimate to what extent V1 neurons are affected by normalization, which was compared against effects of spatial top down attention. For some attention/surround effect comparisons, the strength of attentional modulation was correlated with the strength of surround modulation, suggesting that attention and surround/mask stimulation (i.e. normalization) might use a common mechanism. To explore this in detail, we fitted multiplicative and additive models of attention to our data. In one class of models, attention contributed to normalization mechanisms, whereas in a different class of models it did not. Model selection based on Akaike's and on Bayesian information criteria demonstrated that in most cells the effects of attention were best described by models where attention did not contribute to normalization mechanisms. This demonstrates that attentional influences on neuronal responses in primary visual cortex often bypass normalization mechanisms. PMID:25757941

  5. Radiation protection in decommissioning of the NPP V1

    International Nuclear Information System (INIS)

    Svitek, J.; Kaizer, J.; Siska, J.

    2014-01-01

    What's new in decommissioning of the NPP V1? In 2014 the first stage of the decommissioning should be finished. The program of the first stage was characterized by decommissioning of the non-contaminated facilities and buildings (facilities and buildings out of the control area). However, during the first stage, two key activities were done during which radiation protection had to be especially supervised: BIDSF project - Treatment and Conditioning of Wet Historical Waste - Sludge and Sorbents in the operational tanks NPP V1 (the treatment has been the condition of the regulatory body for the ending of the first stage) and preparation of decontamination of both primary circuits NPP (without reactors). In the year 2015, the second stage of decommissioning should be started. Program for the second stage is broad and it includes fragmentation and treatment of activated parts of the primary circuits (reactors, their internal parts, shielding cassettes). Modification of the radiation protection equipment on the NPP site has been made by BIDSF projects. During the first stage, two basic projects have been done: C12 - Refurbishment of the radiation protection monitoring equipment and C-10 - Free release of decommissioning materials. The present state of monitoring systems, as the result of the aforementioned projects, and the first experiences are main part of this presentation. Another activity, which prepared basic conditions for an execution of radiation protection in the second stage of decommissioning, was the preparation of documents for the procurement of license for the second stage of decommissioning. (authors)

  6. Attention and normalization circuits in macaque V1.

    Science.gov (United States)

    Sanayei, M; Herrero, J L; Distler, C; Thiele, A

    2015-04-01

    Attention affects neuronal processing and improves behavioural performance. In extrastriate visual cortex these effects have been explained by normalization models, which assume that attention influences the circuit that mediates surround suppression. While normalization models have been able to explain attentional effects, their validity has rarely been tested against alternative models. Here we investigate how attention and surround/mask stimuli affect neuronal firing rates and orientation tuning in macaque V1. Surround/mask stimuli provide an estimate to what extent V1 neurons are affected by normalization, which was compared against effects of spatial top down attention. For some attention/surround effect comparisons, the strength of attentional modulation was correlated with the strength of surround modulation, suggesting that attention and surround/mask stimulation (i.e. normalization) might use a common mechanism. To explore this in detail, we fitted multiplicative and additive models of attention to our data. In one class of models, attention contributed to normalization mechanisms, whereas in a different class of models it did not. Model selection based on Akaike's and on Bayesian information criteria demonstrated that in most cells the effects of attention were best described by models where attention did not contribute to normalization mechanisms. This demonstrates that attentional influences on neuronal responses in primary visual cortex often bypass normalization mechanisms. © 2015 The Authors. European Journal of Neuroscience published by Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  7. DISTRIBUTION OF CCR2-64I GENE AMONG THE TRIBES AND CASTE POPULATION OF VIDARBHA, INDIA.

    Directory of Open Access Journals (Sweden)

    Arvind B Chavhan

    2013-08-01

    Results: The genotyping for the CCR2-64I mutation among the selected tribe and a caste reveal that all of the tribes and a caste was found to be heterozygous for the CCR2-64I mutation. Among the tribes Gonds showed highest genotype frequency (29.28% and (11.76% for heterozygous (CCR2/64I and Homozygous (64I/64I respectively, having an allelic frequency (0.233. A pooled allelic frequencies of the wild-type allele CCR2 and CCR2 64I the variant were found to be 0.854 and 0.146, respectively. No significant deviations from the HWE were observed for tribes and a caste population for the CCR2- 64I mutant χ2=2.76. The study reports the presence of mutant CCR2- 64I gene in tribes and caste population from Vidarbha region.

  8. Disposable MagLev centrifugal blood pump utilizing a cone-shaped impeller.

    Science.gov (United States)

    Hijikata, Wataru; Sobajima, Hideo; Shinshi, Tadahiko; Nagamine, Yasuyuki; Wada, Suguru; Takatani, Setsuo; Shimokohbe, Akira

    2010-08-01

    To enhance the durability and reduce the blood trauma of a conventional blood pump with a cone-shaped impeller, a magnetically levitated (MagLev) technology has been applied to the BioPump BPX-80 (Medtronic Biomedicus, Inc., Minneapolis, MN, USA), whose impeller is supported by a mechanical bearing. The MagLev BioPump (MagLev BP), which we have developed, has a cone-shaped impeller, the same as that used in the BPX-80. The suspension and driving system, which is comprised of two degrees of freedom, radial-controlled magnetic bearing, and a simply structured magnetic coupling, eliminates any physical contact between the impeller and the housing. To reduce both oscillation of the impeller and current in the coils, the magnetic bearing system utilizes repetitive and zero-power compensators. In this article, we present the design of the MagLev mechanism, measure the levitational accuracy of the impeller and pressure-flow curves (head-quantity [HQ] characteristics), and describe in vitro experiments designed to measure hemolysis. For the flow-induced hemolysis of the initial design to be reduced, the blood damage index was estimated by using computational fluid dynamics (CFD) analysis. Stable rotation of the impeller in a prototype MagLev BP from 0 to 2750 rpm was obtained, yielding a flow rate of 5 L/min against a head pressure in excess of 250 mm Hg. Because the impeller of the prototype MagLev BP is levitated without contact, the normalized index of hemolysis was 10% less than the equivalent value with the BPX-80. The results of the CFD analysis showed that the shape of the outlet and the width of the fluid clearances have a large effect on blood damage. The prototype MagLev BP satisfied the required HQ characteristics (5 L/min, 250 mm Hg) for extracorporeal circulation support with stable levitation of the impeller and showed an acceptable level of hemolysis. The simulation results of the CFD analysis indicated the possibility of further reducing the blood damage of

  9. MAG4 Versus Alternative Techniques for Forecasting Active-Region Flare Productivity

    Science.gov (United States)

    Falconer, David A.; Moore, Ronald L.; Barghouty, Abdulnasser F.; Khazanov, Igor

    2014-01-01

    MAG4 (Magnetogram Forecast), developed originally for NASA/SRAG (Space Radiation Analysis Group), is an automated program that analyzes magnetograms from the HMI (Helioseismic and Magnetic Imager) instrument on NASA SDO (Solar Dynamics Observatory), and automatically converts the rate (or probability) of major flares (M- and X-class), Coronal Mass Ejections (CMEs), and Solar Energetic Particle Events. MAG4 does not forecast that a flare will occur at a particular time in the next 24 or 48 hours; rather the probability of one occurring.

  10. CD4-independent use of the CCR5 receptor by sequential primary SIVsm isolates

    Directory of Open Access Journals (Sweden)

    Thorstensson Rigmor

    2007-07-01

    Full Text Available Abstract Background CD4-independence has been taken as a sign of a more open envelope structure that is more accessible to neutralizing antibodies and may confer altered cell tropism. In the present study, we analyzed SIVsm isolates for CD4-independent use of CCR5, mode of CCR5-use and macrophage tropism. The isolates have been collected sequentially from 13 experimentally infected cynomolgus macaques and have previously been shown to use CCR5 together with CD4. Furthermore, viruses obtained early after infection were neutralization sensitive, while neutralization resistance appeared already three months after infection in monkeys with progressive immunodeficiency. Results Depending whether isolated early or late in infection, two phenotypes of CD4-independent use of CCR5 could be observed. The inoculum virus (SIVsm isolate SMM-3 and reisolates obtained early in infection often showed a pronounced CD4-independence since virus production and/or syncytia induction could be detected directly in NP-2 cells expressing CCR5 but not CD4 (CD4-independent-HIGH. Conversely, late isolates were often more CD4-dependent in that productive infection in NP-2/CCR5 cells was in most cases weak and was revealed only after cocultivation of infected NP-2/CCR5 cells with peripheral blood mononuclear cells (CD4-independent-LOW. Considering neutralization sensitivity of these isolates, newly infected macaques often harbored virus populations with a CD4-independent-HIGH and neutralization sensitive phenotype that changed to a CD4-independent-LOW and neutralization resistant virus population in the course of infection. Phenotype changes occurred faster in progressor than long-term non-progressor macaques. The phenotypes were not reflected by macrophage tropism, since all isolates replicated efficiently in macrophages. Infection of cells expressing CCR5/CXCR4 chimeric receptors revealed that SIVsm used the CCR5 receptor in a different mode than HIV-1. Conclusion Our

  11. Targeting Spare CC Chemokine Receptor 5 (CCR5) as a Principle to Inhibit HIV-1 Entry*

    OpenAIRE

    Jin, Jun; Colin, Philippe; Staropoli, Isabelle; Lima-Fernandes, Evelyne; Ferret, Cécile; Demir, Arzu; Rogée, Sophie; Hartley, Oliver; Randriamampita, Clotilde; Scott, Mark G. H.; Marullo, Stefano; Sauvonnet, Nathalie; Arenzana-Seisdedos, Fernando; Lagane, Bernard; Brelot, Anne

    2014-01-01

    International audience; : CCR5 binds the chemokines CCL3, CCL4, and CCL5 and is the major coreceptor for HIV-1 entry into target cells. Chemokines are supposed to form a natural barrier against human immunodeficiency virus, type 1 (HIV-1) infection. However, we showed that their antiviral activity is limited by CCR5 adopting low-chemokine affinity conformations at the cell surface. Here, we investigated whether a pool of CCR5 that is not stabilized by chemokines could represent a target for i...

  12. The chemokine receptor CCR5 Δ32 allele in natalizumab-treated multiple sclerosis

    DEFF Research Database (Denmark)

    Møller, M; Søndergaard, Helle B; Koch-Henriksen, N

    2014-01-01

    OBJECTIVE: The chemokine receptor CCR5 may be important for the recruitment of pathogenic T cells to the CNS in multiple sclerosis (MS). We hypothesized that this chemokine receptor might still be important for T-cell migration during treatment with anti-very late antigen (VLA)-4 antibody. We...... impact on the frequency of relapses 1 year prior to natalizumab treatment or during the first 48 weeks of treatment. The multiple sclerosis severity score (MSSS) was significantly lower at baseline in patients carrying CCR5 Δ32 (P = 0.031). CONCLUSIONS: CCR5 Δ32 is not associated with lower disease...

  13. CCL3L1 copy number, CCR5 genotype and susceptibility to tuberculosis

    OpenAIRE

    Carpenter, Danielle; Taype, Carmen; Goulding, Jon; Levin, Mike; Eley, Brian; Anderson, Suzanne; Shaw, Marie-Anne; Armour, John AL

    2014-01-01

    Background: Tuberculosis is a major infectious disease and functional studies have provided evidence that both the chemokine MIP-1α and its receptor CCR5 play a role in susceptibility to TB. Thus by measuring copy number variation of CCL3L1, one of the genes that encode MIP-1α, and genotyping a functional promoter polymorphism -2459A > G in CCR5 (rs1799987) we investigate the influence of MIP-1α and CCR5, independently and combined, in susceptibility to clinically active TB in three populatio...

  14. Association between the CCR5 32-bp deletion allele and late onset of schizophrenia

    DEFF Research Database (Denmark)

    Rasmussen, Henrik Berg; Timm, Sally; Wang, August G

    2006-01-01

    OBJECTIVE: The 32-bp deletion allele in chemokine receptor CCR5 has been associated with several immune-mediated diseases and might be implicated in schizophrenia as well. METHOD: The authors genotyped DNA samples from 268 schizophrenia patients and 323 healthy subjects. Age at first admission...... of the deletion allele in the latter subgroup of patients. CONCLUSIONS: These findings suggest that the CCR5 32-bp deletion allele is a susceptibility factor for schizophrenia with late onset. Alternatively, the CCR5 32-bp deletion allele may act as a modifier by delaying the onset of schizophrenia without...

  15. A CCR2 macrophage endocytic pathway mediates extravascular fibrin clearance in vivo

    DEFF Research Database (Denmark)

    Motley, Michael P; Madsen, Daniel H; Jürgensen, Henrik J

    2016-01-01

    cellular endocytosis and lysosomal targeting, revealing a novel intracellular pathway for extravascular fibrin degradation. A C-C chemokine receptor type 2 (CCR2)-positive macrophage subpopulation constituted the majority of fibrin-uptaking cells. Consequently, cellular fibrin uptake was diminished...... by elimination of CCR2-expressing cells. The CCR2-positive macrophage subtype was different from collagen-internalizing M2-like macrophages. Cellular fibrin uptake was strictly dependent on plasminogen and plasminogen activator. Surprisingly, however, fibrin endocytosis was unimpeded by the absence of the fibrin...... subsets of macrophages employing distinct molecular pathways....

  16. Backfitting of Nuclear Power Plant Bohunice V1 in Slovakia

    International Nuclear Information System (INIS)

    Ferenc, M.

    1999-01-01

    Nuclear power plants in the Slovak Republic generate almost 55 % of electricity. The operating organization and the Nuclear Regulatory Authority of the Slovak Republic pay a great attention to safe and reliable operation of four units with VVER 440 reactors at Bohunices site and one in Mochovce side. Engineering and design organizations in cooperation with well known international companies prepare evaluation of safety conditions, safety analyses and projects for the implementation of modifications to upgrade the nuclear safety of the units in operation. A gradual safety upgrading (reconstruction) of the V-1 Bohunice plant has been in progress, a modernization of the V-2 Bohunice plant is being prepared. Simultaneously the commissioning of Unit 2 at the Mochovce plant is being implemented.(author)

  17. REKO - Bohunice V-1. Experience with instrumentation and control system

    International Nuclear Information System (INIS)

    Arbet, L.; Ziska, D.; Golan, P.; Karaba, P.; Krupa, S.; Wiening, K.-H.

    2000-01-01

    In this paper and in presentation some results of upgrading of the NPP Bohunice V-1 are presented. For the first time, extensive upgrades are performed in all safety-related areas of both units with VVER 440/230 reactors. These upgrades focused on: - Expansion and upgrading of the process safety systems; - Replacement of the safety I and C system with a TELEPERM XS-based system; - Spatial separation of safety equipment; - Modernisation of the electrical auxiliary power systems; - Seismic upgrading and fire protection; - Improvement of the man-machine interface. This upgrade is considered exemplary around the world. The most extensive stage of gradual reconstruction of Unit 2 was completed according to the schedule in January 1999. For the first time, a reactor which incorporates state-of-the-art digital I and C in its reactor protection system is on-line. (author)

  18. The V-1 NPP and V-2 NPP upgrading

    International Nuclear Information System (INIS)

    1998-01-01

    A brief account of activities in the V-1 NPP and V-2 NPP upgrading as well as maintenance carried out by the Nuclear power plants Jaslovske Bohunice in 1997 is presented. The V-1 NPP applied the so called 'Small Backfitting Programme'covering 81 points of the Czechoslovak Atomic energy Commission Decree No 5/91. Continual upgrading continued after the Backfitting Programme completion with the Safety Report and following Nuclear Regulatory Authority of Slovak Republic (NRA SR) Decrees No 1/94 and 110/94 setting spheres and procedure for adopting and implementation of measures enabling the units to operate further on. Results of expert missions, analyses and assessments of components identified by Basic Engineering became the basis for the development of the Gradual Reconstruction Programme. The Programme outputs underwent economic and probabilistic assessing their contribution to nuclear safety. This process resulted in finalizing the Gradual Reconstruction Programme which started to be implemented in 1996 and will be completed in 1999. It is implemented by the REKON consortium and covers 17 areas including Instrumentation and Control, self-consumption emergency supply, leakage monitoring, emergency core cooling system, seismic reinforcement and radioactivity localisation. Both units will reach internationally acceptable safety standards for the remaining life-time period. The V-2 NPP Upgrading and Safety Enhancement Programme includes results of activities performed in the course of last years to define all important activities leading to enhancement of nuclear safety and performance reliability and effectiveness within the plant life-time period and to establish conditions for extending the life-time of these units for 40 years. The V-2 NPP Upgrading and Safety Enhancement Programme aims to assure safe operation with a probability of the core damages less than 10 -4 /reactor · year

  19. Chemokine CCL2 and chemokine receptor CCR2 in early active multiple sclerosis

    DEFF Research Database (Denmark)

    Sørensen, Torben Lykke; Ransohoff, R M; Strieter, R M

    2004-01-01

    The chemokine monocyte chemoattractant protein (MCP)-1/CCL2 and its receptor CCR2 have been strongly implicated in disease pathogenesis in experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis (MS), whereas data on the CCL2-CCR2 axis are scarce in MS. We studied...... the expression of CCR2 on leukocytes in blood and cerebrospinal fluid (CSF) from patients with monosymptomatic optic neuritis and MS, and the concentration of CCL2 in the CSF from these patients. Results were compared with the results in non-inflammatory neurological controls and were correlated with other...... parameters (magnetic resonance imaging and CSF data). Our findings suggest a limited role for CCL2/CCR2 in early active MS....

  20. [Novel echogenic needle for ultrasound-guided peripheral nerve block "Hakko type CCR"].

    Science.gov (United States)

    Takayama, Wataru; Yasumura, Rie; Kaneko, Takehiko; Kobayashi, Yoshiro; Kamada, Takaaki; Yoshikawa, Tamotsu; Aoyama, Yasuhiko

    2009-04-01

    A novel echogenic insulated nerve block needle (CCR-needle: Echogenic Needle Type CCR; Hakko, Japan) is commercially available since 2006 in Japan. This needle has three echogenic dimples, namely corner cube reflectors (CCR) on its tip. The CCR-needle will potentially provide a significant advantage for detecting the needle tip. In this report, we firstly evaluated this new disposable echogenic needle in simulation phantom, and demonstrated improved visibility of the needle tip. Afterwards, an interscalene brachial plexus block was performed on a male patient undergoing shoulder surgery. The needle insertion procedure was the "out of plane" ultrasound-guided technique using simultaneous electrical nerve stimulation. The surgery was successfully conducted without any complications.

  1. Study progress of CCR3 in wet age-related macular degeneration

    Directory of Open Access Journals (Sweden)

    Xian-Wei Wu

    2014-03-01

    Full Text Available According to the study, chemokine receptor 3(CCR3in the eye is mainly distributed in retinal pigment epithelial cells, and also expressed in the choroidal vascular endothelial cells(CECs. The specificity of CCR3's high expression in wet age-related macular degeneration(AMDwas found, and it is proved that in wet-AMD patients, it plays an important role in the formation of choroidal neovascularization(CNV. In this paper, the structure, function, the problem of current research and the future direction of CCR3 were summarized. It is believed that with the further research on CCR3, it will not only help us to find a new method of wet-AMD diagnosis and treatment, but also may provide an important reference for other CNV disease research and new anti-CNV drugs.

  2. Spectroscopic Analysis of 10MAG/LDAO Reverse Micelles to Determine Characteristic Properties and Behavioral Extrema

    Science.gov (United States)

    Berg, Joshua; Mawson, Cara; Norris, Zach; Nucci, Nathaniel

    Reverse micelles are spontaneously organizing complexes of surfactant that encapsulate a nanoscale pool of water in a bulk non-polar solvent. Reverse micelle (RM) mixtures have a wide range of applications, including biophysical investigation of protein systems. A new RM mixture composed of decyl-1-monoglycerol (10MAG) and lauryldimethylammonium-N-oxide (LDAO) was recently described. This mixture has the potential to prove more widely applicable for use of RMs in applications that involve encapsulation of macromolecules, yet little is known about the phase behavior or size of reverse micelles created by this mixture. Data describing such behaviors for this mixture are presented here. We have used dynamic light scattering (DLS) and fluorescence spectroscopy to investigate the size and partitioning behavior of RMs in varying mixtures of 10MAG, LDAO, water, pentane, and hexanol. These data demonstrate that the 10MAG/LDAO RM mixture exhibits markedly different phase and RM size behavior than that of commonly used RM surfactant mixtures. The implications of these findings for use of the 10MAG/LDAO mix for RM applications will also be addressed. Funding provided by Rowan University.

  3. {sup 110m}Ag root and foliar uptake in vegetables and its migration in soil

    Energy Technology Data Exchange (ETDEWEB)

    Shang, Z.R.; Leung, J.K.C. E-mail: jkcleung@hku.hk

    2003-07-01

    {sup 110m}Ag, as a radionuclide of corrosion products in water-cooled nuclear reactors, was detected in the liquid effluents of Guangdong Daya Bay Nuclear Power Station (GNPS) of Daya Bay under normal operation conditions. Experiments on a simulated terrestrial agricultural ecosystem were carried out using the pot experiment approach. The most common plants in Hong Kong and the South China vegetable gardens such as lettuce, Chinese spinach, kale, carrot, pepper, eggplant, bean, flowering cabbage, celery, European onion and cucumber were selected for {sup 110m}Ag root and foliar uptake tests. The results show that carrot, kale and flowering cabbage have the greatest values of soil to plant transfer factor among the vegetables, while{sup 110m}Ag can be transferred to Chinese spinach via foliar uptake. Flowering cabbage, the most popular leafy vegetable locally, could be used as a biomonitor for the radioisotope contamination in vegetables. Soil column and adsorption tests were also carried out to study the leaching ability and distributio coefficient (K{sub d}) of {sup 110m}Ag in the soil. The results show that most of the radionuclide was adsorbed in the top 1 cm of soil regardless of the pH value. The K{sub d} was also determined.

  4. Interaction of both plasmas in CO2 laser-MAG hybrid welding of carbon steel

    Science.gov (United States)

    Kutsuna, Muneharu; Chen, Liang

    2003-03-01

    Researches and developments of laser and arc hybrid welding has been curried out since in 1978. Especially, CO2 laser and TIG hybrid welding has been studied for increasing the penetration depth and welding speed. Recently laser and MIG/MAG/Plasma hybrid welding processes have been developed and applied to industries. It was recognized as a new welding process that promote the flexibility of the process for increasing the penetration depth, welding speed and allowable joint gap and improving the quality of the welds. In the present work, CO2 Laser-MAG hybrid welding of carbon steel (SM490) was investigated to make clear the phenomenon and characteristics of hybrid welding process comparing with laser welding and MAG process. The effects of many process parameters such as welding current, arc voltage, welding speed, defocusing distance, laser-to-arc distance on penetration depth, bead shape, spatter, arc stability and plasma formation were investigated in the present work. Especially, the interaction of laser plasma and MAG arc plasma was considered by changing the laser to arc distance (=DLA).

  5. Status analysis of keyhole bottom in laser-MAG hybrid welding process.

    Science.gov (United States)

    Wang, Lin; Gao, Xiangdong; Chen, Ziqin

    2018-01-08

    The keyhole status is a determining factor of weld quality in laser-metal active gas arc (MAG) hybrid welding process. For a better evaluation of the hybrid welding process, three different penetration welding experiments: partial penetration, normal penetration (or full penetration), and excessive penetration were conducted in this work. The instantaneous visual phenomena including metallic vapor, spatters and keyhole of bottom surface were used to evaluate the keyhole status by a double high-speed camera system. The Fourier transform was applied on the bottom weld pool image for removing the image noise around the keyhole, and then the bottom weld pool image was reconstructed through the inverse Fourier transform. Lastly, the keyhole bottom was extracted from the de-noised bottom weld pool image. By analyzing the visual features of the laser-MAG hybrid welding process, mechanism of the closed and opened keyhole bottom were revealed. The results show that the stable opened or closed status of keyhole bottom is directly affected by the MAG droplet transition in the normal penetration welding process, and the unstable opened or closed status of keyhole bottom would appear in excessive penetration welding and partial penetration welding. The analysis method proposed in this paper could be used to monitor the keyhole stability in laser-MAG hybrid welding process.

  6. In-situ remediation of contaminated ground water using the MAG*SEPSM technology

    International Nuclear Information System (INIS)

    Dunn, M.J.

    1994-01-01

    Argonne National Laboratory is leading a project for demonstration of in-situ remediation of contaminated ground water utilizing MAG*SEP SM technology developed by Bradtec. This technology is being considered for eventual application at sites involving groundwater contaminated with heavy metals and/or radionuclides, such as the Savannah River Site (SRS) and Berkeley Pit. The MAG*SEP SM technology uses specially coated magnetic particles to selectively adsorb contaminants from ground water. Particles are mixed with ground water, contaminants are adsorbed onto the particles, and the particles are removed by magnetic filtration. The technology can recover low levels of radioactive and/or inorganic hazardous contamination (in the ppm range), leaving nonradioactive/nonhazardous species essentially unaffected. The first phase of this project has involved the optimization of MAG*SEP SM process chemistry for a selected site at SRS. To date this work has identified a candidate adsorber material (the amino form of iminodicarboxylic acid) for selective removal of lead, cadmium, and mercury from this site's ground water. Decontamination factors of 170, 270, and 235, respective, for each contaminant have been achieved. Further process chemistry optimization work for this adsorber material is planned. The project will eventually lead to an in-situ demonstration of the MAG*SEP SM technology, integrated with the EnviroWall trademark barrier technology developed by Barrier Member Containment Corporation (BMC)

  7. FastMag: Fast micromagnetic simulator for complex magnetic structures (invited)

    Science.gov (United States)

    Chang, R.; Li, S.; Lubarda, M. V.; Livshitz, B.; Lomakin, V.

    2011-04-01

    A fast micromagnetic simulator (FastMag) for general problems is presented. FastMag solves the Landau-Lifshitz-Gilbert equation and can handle multiscale problems with a high computational efficiency. The simulator derives its high performance from efficient methods for evaluating the effective field and from implementations on massively parallel graphics processing unit (GPU) architectures. FastMag discretizes the computational domain into tetrahedral elements and therefore is highly flexible for general problems. The magnetostatic field is computed via the superposition principle for both volume and surface parts of the computational domain. This is accomplished by implementing efficient quadrature rules and analytical integration for overlapping elements in which the integral kernel is singular. Thus, discretized superposition integrals are computed using a nonuniform grid interpolation method, which evaluates the field from N sources at N collocated observers in O(N) operations. This approach allows handling objects of arbitrary shape, allows easily calculating of the field outside the magnetized domains, does not require solving a linear system of equations, and requires little memory. FastMag is implemented on GPUs with ?> GPU-central processing unit speed-ups of 2 orders of magnitude. Simulations are shown of a large array of magnetic dots and a recording head fully discretized down to the exchange length, with over a hundred million tetrahedral elements on an inexpensive desktop computer.

  8. Haplotypes in CCR5-CCR2, CCL3 and CCL5 are associated with natural resistance to HIV-1 infection in a Colombian cohort.

    Science.gov (United States)

    Vega, Jorge A; Villegas-Ospina, Simón; Aguilar-Jiménez, Wbeimar; Rugeles, María T; Bedoya, Gabriel; Zapata, Wildeman

    2017-06-01

    Variants in genes encoding for HIV-1 co-receptors and their natural ligands have been individually associated to natural resistance to HIV-1 infection. However, the simultaneous presence of these variants has been poorly studied. To evaluate the association of single and multilocus haplotypes in genes coding for the viral co-receptors CCR5 and CCR2, and their ligands CCL3 and CCL5, with resistance or susceptibility to HIV-1 infection. Nine variants in CCR5-CCR2, two SNPs in CCL3 and two in CCL5 were genotyped by PCR-RFLP in 35 seropositive (cases) and 49 HIV-1-exposed seronegative Colombian individuals (controls). Haplotypes were inferred using the Arlequin software, and their frequency in individual or combined loci was compared between cases and controls by the chi-square test. A p' value ;0.05 after Bonferroni correction was considered significant. Homozygosis of the human haplogroup (HH) E was absent in controls and frequent in cases, showing a tendency to susceptibility. The haplotypes C-C and T-T in CCL3 were associated with susceptibility (p'=0.016) and resistance (p';0.0001) to HIV-1 infection, respectively. Finally, in multilocus analysis, the haplotype combinations formed by HHC in CCR5-CCR2, T-T in CCL3 and G-C in CCL5 were associated with resistance (p'=0.006). Our results suggest that specific combinations of variants in genes from the same signaling pathway can define an HIV-1 resistant phenotype. Despite our small sample size, our statistically significant associations suggest strong effects; however, these results should be further validated in larger cohorts.

  9. Residual kidney function after donor nephrectomy. Assessment by 99mTc-MAG3-Clearance

    International Nuclear Information System (INIS)

    Hamscho, N.; Doebert, N.; Menzel, C.; Berner, U.; Zaplatnikov, K.; Gruenwald, F.; Wilhelm, A.; Gossmann, J.; Scheuermann, E.H.

    2005-01-01

    Aim: We evaluated the long-term residual renal function after donor nephrectomy using 99m Tc-mercaptoacetyltriglycin (MAG3)-clearance. Donors, methods: Altogether 49 kidney donors were examined using 99m Tc-MAG3-clearance after nephrectomy for donation to a relative (m:f=11.38; age 55±27 years). The donors were examined 16±8 years postoperatively (1.5-26 years). 42 donors (86%) showed normal creatinine values, whereas the other seven (14%) exhibited slightly elevated levels. 20 donors were examined pre- and postoperatively and compared intraindividually. The kidney function was compared to the age adapted normal values of healthy persons with two kidneys (67-133% of age related mean). Results: After nephrectomy all donors showed a normal perfusion, good secretion, merely physiological intrarenal transit and a normal elimination from the kidneys. The 99m Tc-MAG3-clearance was 69±15% of the normal mean value of healthy carriers of two kidneys regardless of the gender. 20 donors with a preoperative examination showed a significantly reduced total renal function from 84±15% of the mean normal value preoperatively to 60±15% postoperatively (p 99m Tc-MAG3-clearance measured prior to nephrectomy and the clearance levels after nephrectomy. Also, no correlation between the preoperative 99m Tc-MAG3-clearance and the postoperative serum creatinine values could be observed. Althogether, 22% of the donors (11/49) developed arterial hypertension 10±8 years after donation (1-23 years). This corresponds to the normal age prevalence of hypertension in the carriers of two kidneys. Three donors suffered from arterial hypertension prior to the operation. Conclusion: Kidney donors with normal or slightly elevated creatinine values postoperatively show a 99m Tc-MAG3 clearance value of 69% of the mean value of healthy carriers of two kidneys. This may serve as a reference value for healthy carriers of one kidney. In our study we demonstrated a good compensation of the contralateral

  10. CCR5 receptor antagonists: discovery and SAR study of guanylhydrazone derivatives.

    Science.gov (United States)

    Wei, Robert G; Arnaiz, Damian O; Chou, Yuo-Ling; Davey, Dave; Dunning, Laura; Lee, Wheeseong; Lu, Shou-Fu; Onuffer, James; Ye, Bin; Phillips, Gary

    2007-01-01

    High throughput screening (HTS) led to the identification of the guanylhydrazone of 2-(4-chlorobenzyloxy)-5-bromobenzaldehyde as a CCR5 receptor antagonist. Initial modifications of the guanylhydrazone series indicated that substitution of the benzyl group at the para-position was well tolerated. Substitution at the 5-position of the central phenyl ring was critical for potency. Replacement of the guanylhydrazone group led to the discovery of a novel series of CCR5 antagonists.

  11. Ccr2 deletion dissociates cavity size and tau pathology after mild traumatic brain injury.

    Science.gov (United States)

    Gyoneva, Stefka; Kim, Daniel; Katsumoto, Atsuko; Kokiko-Cochran, O Nicole; Lamb, Bruce T; Ransohoff, Richard M

    2015-12-03

    Millions of people experience traumatic brain injury (TBI) as a result of falls, car accidents, sports injury, and blast. TBI has been associated with the development of neurodegenerative conditions such as Alzheimer's disease (AD) and chronic traumatic encephalopathy (CTE). In the initial hours and days, the pathology of TBI comprises neuronal injury, breakdown of the blood-brain barrier, and inflammation. At the cellular level, the inflammatory reaction consists of responses by brain-resident microglia, astrocytes, and vascular elements as well as infiltration of peripheral cells. After TBI, signaling by chemokine (C-C motif) ligand 2 (CCL2) to the chemokine (C-C motif) receptor 2 (CCR2) is a key regulator of brain infiltration by monocytes. We utilized mice with one or both copies of Ccr2 disrupted by red fluorescent protein (RFP, Ccr2 (RFP/+) and Ccr2 (RFP/RFP) ). We subjected these mice to the mild lateral fluid percussion model of TBI and examined several pathological outcomes 3 days later in order to determine the effects of altered monocyte entry into the brain. Ccr2 deletion reduced monocyte infiltration, diminished lesion cavity volume, and lessened axonal damage after mild TBI, but the microglial reaction to the lesion was not affected. We further examined phosphorylation of the microtubule-associated protein tau, which aggregates in brains of people with TBI, AD, and CTE. Surprisingly, Ccr2 deletion was associated with increased tau mislocalization to the cell body in the cortex and hippocampus by tissue staining and increased levels of phosphorylated tau in the hippocampus by Western blot. Disruption of CCR2 enhanced tau pathology and reduced cavity volume in the context of TBI. The data reveal a complex role for CCR2(+) monocytes in TBI, as monitored by cavity volume, axonal damage, and tau phosphorylation.

  12. Frequency of CCR5Δ32 allele in healthy Bosniak population.

    Directory of Open Access Journals (Sweden)

    Grażyna Adler

    2014-08-01

    Full Text Available Recent evidence has demonstrated the role of CCR5Δ32 in a variety of human diseases: from infectious and inflammatory diseases to cancer. Several studies have confirmed that genetic variants in chemokine receptor CCR5 gene are correlated with susceptibility and resistance to HIV infection. A 32-nucleotide deletion within the CCR5 reading frame is associated with decreased susceptibility to HIV acquisition and a slower progression to AIDS. Mean frequency of CCR5Δ32 allele in Europe is approximately 10%. The highest allele frequency is observed among Nordic populations (about 12% and lower in the regions of Southeast Mediterranean (about 5%. Although the frequency of CCR5Δ32 was determined in numerous European populations, there is a lack of studies on this variant in the Bosnia and Hercegovina population. Therefore, the aim of our study was to assess the frequency of CCR5Δ32 allele in the cohort of Bosniaks and compare the results with European reports. CCR5Δ32 was detected by sequence-specific PCR in a sample of 100 healthy subjects from Bosnia and Herzegovina (DNA collected 2011-2013.  Mean age of the cohort being 58.8 (±10.7 years, with 82% of women. We identified 17 heterozygotes and one mutant homozygote in study group, with mean ∆32 allele frequency of 9.5%. CCR5∆32 allele frequency among Bosniaks is comparable to that found in Caucasian populations and follows the pattern of the north-southern gradient observed for Europe. Further studies on larger cohorts with adequate female-to-male ratio are necessary. 

  13. VEGF-production by CCR2-dependent macrophages contributes to laser-induced choroidal neovascularization.

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    Torsten A Krause

    Full Text Available Age-related macular degeneration (AMD is the most prevalent cause of blindness in the elderly, and its exsudative subtype critically depends on local production of vascular endothelial growth factor A (VEGF. Mononuclear phagocytes, such as macrophages and microglia cells, can produce VEGF. Their precursors, for example monocytes, can be recruited to sites of inflammation by the chemokine receptor CCR2, and this has been proposed to be important in AMD. To investigate the role of macrophages and CCR2 in AMD, we studied intracellular VEGF content in a laser-induced murine model of choroidal neovascularisation. To this end, we established a technique to quantify the VEGF content in cell subsets from the laser-treated retina and choroid separately. 3 days after laser, macrophage numbers and their VEGF content were substantially elevated in the choroid. Macrophage accumulation was CCR2-dependent, indicating recruitment from the circulation. In the retina, microglia cells were the main VEGF+ phagocyte type. A greater proportion of microglia cells contained VEGF after laser, and this was CCR2-independent. On day 6, VEGF-expressing macrophage numbers had already declined, whereas numbers of VEGF+ microglia cells remained increased. Other sources of VEGF detectable by flow cytometry included in dendritic cells and endothelial cells in both retina and choroid, and Müller cells/astrocytes in the retina. However, their VEGF content was not increased after laser. When we analyzed flatmounts of laser-treated eyes, CCR2-deficient mice showed reduced neovascular areas after 2 weeks, but this difference was not evident 3 weeks after laser. In summary, CCR2-dependent influx of macrophages causes a transient VEGF increase in the choroid. However, macrophages augmented choroidal neovascularization only initially, presumably because VEGF production by CCR2-independent eye cells prevailed at later time points. These findings identify macrophages as a relevant source

  14. Lack of association between the chemokine receptor 5 polymorphism CCR5delta32 in rheumatoid arthritis and juvenile idiopathic arthritis

    Directory of Open Access Journals (Sweden)

    Kvien Tore K

    2007-06-01

    Full Text Available Abstract Background The chemokine receptor CCR5 has been detected at elevated levels on synovial T cells, and a 32 bp deletion in the CCR5 gene leads to a non-functional receptor. A negative association between the CCR5Δ32 and rheumatoid arthritis (RA has been reported, although with conflicting results. In juvenile idiopathic arthritis (JIA, an association with CCR5 was recently reported. The purpose of this study was to investigate if the CCR5Δ32 polymorphism is associated with RA or JIA in Norwegian cohorts. Methods 853 RA patients, 524 JIA patients and 658 controls were genotyped for the CCR5Δ32 polymorphism. Results The CCR5Δ32 allele frequency was 11.5% in the controls vs. 10.4% in RA patients (OR = 0.90; P = 0.36 and 9.7% in JIA patients (OR = 0.85; P = 0.20. No decreased homozygosity was observed for CCR5Δ32, as previously suggested. Conclusion Our data do not support an association between the CCR5Δ32 allele and Norwegian RA or JIA patients. Combining our results with those from a recently published meta-analysis still provide evidence for a role for CCR5Δ32 in RA, albeit substantially weaker than the effect first reported.

  15. 76 FR 46330 - NUREG-1934, Nuclear Power Plant Fire Modeling Application Guide (NPP FIRE MAG); Second Draft...

    Science.gov (United States)

    2011-08-02

    ... NUCLEAR REGULATORY COMMISSION [NRC-2009-0568] NUREG-1934, Nuclear Power Plant Fire Modeling... 1023259), ``Nuclear Power Plant Fire Modeling Application Guide (NPP FIRE MAG), Second Draft Report for...), ``Nuclear Power Plant Fire Modeling Application Guide (NPP FIRE MAG), Second Draft for Comment,'' is...

  16. CCL5 and CCR5 interaction promotes cell motility in human osteosarcoma.

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    Shih-Wei Wang

    Full Text Available BACKGROUND: Osteosarcoma is characterized by a high malignant and metastatic potential. CCL5 (previously called RANTES was originally recognized as a product of activated T cells, and plays a crucial role in the migration and metastasis of human cancer cells. It has been reported that the effect of CCL5 is mediated via CCR receptors. However, the effect of CCL5 on migration activity and integrin expression in human osteosarcoma cells is mostly unknown. METHODOLOGY/PRINCIPAL FINDINGS: Here we found that CCL5 increased the migration and expression of αvβ3 integrin in human osteosarcoma cells. Stimulation of cells with CCL5 increased CCR5 but not CCR1 and CCR3 expression. CCR5 mAb, inhibitor, and siRNA reduced the CCL5-enhanced the migration and integrin up-regulation of osteosarcoma cells. Activations of MEK, ERK, and NF-κB pathways after CCL5 treatment were demonstrated, and CCL5-induced expression of integrin and migration activity was inhibited by the specific inhibitor and mutant of MEK, ERK, and NF-κB cascades. In addition, over-expression of CCL5 shRNA inhibited the migratory ability and integrin expression in osteosarcoma cells. CONCLUSIONS/SIGNIFICANCE: CCL5 and CCR5 interaction acts through MEK, ERK, which in turn activates NF-κB, resulting in the activations of αvβ3 integrin and contributing the migration of human osteosarcoma cells.

  17. Functional characterization of CCR in birch (Betula platyphylla × Betula pendula) through overexpression and suppression analysis.

    Science.gov (United States)

    Zhang, Wenbo; Wei, Rui; Chen, Su; Jiang, Jing; Li, Huiyu; Huang, Haijiao; Yang, Guang; Wang, Shuo; Wei, Hairong; Liu, Guifeng

    2015-06-01

    We cloned a Cinnamoyl-CoA Reductase gene (BpCCR1) from an apical meristem and first internode of Betula platyphylla and characterized its functions in lignin biosynthesis, wood formation and tree growth through transgenic approaches. We generated overexpression and suppression transgenic lines and analyzed them in comparison with the wild-type in terms of lignin content, anatomical characteristics, height and biomass. We found that BpCCR1 overexpression could increase lignin content up to 14.6%, and its underexpression decreased lignin content by 6.3%. Surprisingly, modification of BpCCR1 expression led to conspicuous changes in wood characteristics, including xylem vessel number and arrangement, and secondary wall thickness. The growth of transgenic trees in terms of height was also significantly influenced by the modification of BpCCR1 genes. We discuss the functions of BpCCR1 in the context of a phylogenetic tree built with CCR genes from multiple species. © 2014 Scandinavian Plant Physiology Society.

  18. CCR2-V64I genetic polymorphism: a possible involvement in HER2+ breast cancer.

    Science.gov (United States)

    Banin-Hirata, Bruna Karina; Losi-Guembarovski, Roberta; Oda, Julie Massayo Maeda; de Oliveira, Carlos Eduardo Coral; Campos, Clodoaldo Zago; Mazzuco, Tânia Longo; Borelli, Sueli Donizete; Ceribelli, Jesus Roberto; Watanabe, Maria Angelica Ehara

    2016-05-01

    Many tumor cells express chemokines and chemokine receptors, and these molecules can affect both tumor progression and anti-tumor immune response. Genetic polymorphisms of some chemokine receptors were found to be closely related to malignant tumors, especially in metastasis process, including breast cancer (BC). Considering this, it was investigated a possible role for CCR2-V64I (C-C chemokine receptor 2) and CCR5-Δ32 (C-C chemokine receptor 5) genetic variants in BC context. Patients were divided into subgroups according to immunohistochemical profile of estrogen (ER) and progesterone (PR) receptors and the human epidermal growth factor receptor 2 (HER2) overexpression. No significant associations were found in relation to susceptibility (CCR2-V64I: OR 1.32; 95 % CI 0.57-3.06; CCR5-∆32: OR 1.04; 95 % CI 0.60-1.81), clinical outcome (tumor size, lymph nodes commitment and/or distant metastasis, TNM staging and nuclear grade) or therapeutic response (recurrence and survival). However, it was found a significant correlation between CCR2-V64I allelic variant and HER2 immunohistochemical positive samples (p = 0.026). All in all, we demonstrate, for the first time, a positive correlation between CCR2 receptor gene polymorphism and a subgroup of BC related to poor prognosis, which deserves further investigation in larger samples for validation.

  19. CCR5 Targeted Cell Therapy for HIV and Prevention of Viral Escape

    Directory of Open Access Journals (Sweden)

    Gero Hütter

    2015-07-01

    Full Text Available Allogeneic transplantation with CCR5-delta 32 (CCR5-d32 homozygous stem cells in an HIV infected individual in 2008, led to a sustained virus control and probably eradication of HIV. Since then there has been a high degree of interest to translate this approach to a wider population. There are two cellular ways to do this. The first one is to use a CCR5 negative cell source e.g., hematopoietic stem cells (HSC to copy the initial finding. However, a recent case of a second allogeneic transplantation with CCR5-d32 homozygous stem cells suffered from viral escape of CXCR4 quasi-species. The second way is to knock down CCR5 expression by gene therapy. Currently, there are five promising techniques, three of which are presently being tested clinically. These techniques include zinc finger nucleases (ZFN, clustered regularly interspaced palindromic repeats/CRISPR-associated protein 9 nuclease (CRISPR/Cas9, transcription activator-like effectors nuclease (TALEN, short hairpin RNA (shRNA, and a ribozyme. While there are multiple gene therapy strategies being tested, in this review we reflect on our current knowledge of inhibition of CCR5 specifically and whether this approach allows for consequent viral escape.

  20. ICARE/CATHARE V1: Capabilities and applications

    International Nuclear Information System (INIS)

    Zabiego, M.; Guillard, V.; Fichot, F.; Marchand, O.; Chatelard, P.; Camous, F.; Barre, F.; Lefevre, B.

    2001-01-01

    The ICARE/CATHARE code is designed to calculate in a mechanistic way reactor core damage and primary circuit behaviour in PWRs. It is developed at the French Institute for Nuclear Protection and Safety (IPSN), as an analytical support of the in-pile experimental PHEBUS programs and for studies of reactor sequences in nuclear reactors. ICARE/CATHARE V1 includes the latest version of ICARE2 (V3Mod0) which features a comprehensive set of models for late degradation allowing to follow the materials from their early melting in the core region to their later relocation into the lower plenum. It also includes the thermal-hydraulics code CATHAREZ (V1.3L/b 1) which enables to take into account the whole primary circuit and its impact on the degradation. ICARE2 describes a set of components representing either the vessel structures (fuel and control rods, barrel, vessel, etc.) or the solid debris, or the melt, or the gas. The vessel volume is discretized on a two-dimensional cylindrical meshing. Each component is described by its volume fraction in the mesh, its composition and its temperature. The solid components also have a specific geometry: rods are represented as cylinders, debris particles as a set of spheres, etc.. Several applications have already been performed, either with the stand-alone version of ICARE2 or with the coupled ICARE/CATHARE version. An application of the coupled version to the calculation of the first two phases of the TMI2 accident is presented. It shows that the coupling enables both codes to extend their range of application towards the complete calculation of a severe accident sequence. Although the calculation could not be performed up to the late degradation phase, it proves the operability of the coupled version. The results are in good agreement with TMI data during the LOCA phase, and the core uncover and degradation phenomena are qualitatively well reproduced. An application of the stand-alone ICARE2 version, including all the late

  1. Collinear integration affects visual search at V1.

    Science.gov (United States)

    Chow, Hiu Mei; Jingling, Li; Tseng, Chia-huei

    2013-08-29

    Perceptual grouping plays an indispensable role in figure-ground segregation and attention distribution. For example, a column pops out if it contains element bars orthogonal to uniformly oriented element bars. Jingling and Tseng (2013) have reported that contextual grouping in a column matters to visual search behavior: When a column is grouped into a collinear (snakelike) structure, a target positioned on it became harder to detect than on other noncollinear (ladderlike) columns. How and where perceptual grouping interferes with selective attention is still largely unknown. This article contributes to this little-studied area by asking whether collinear contour integration interacts with visual search before or after binocular fusion. We first identified that the previously mentioned search impairment occurs with a distractor of five or nine elements but not one element in a 9 × 9 search display. To pinpoint the site of this effect, we presented the search display with a short collinear bar (one element) to one eye and the extending collinear bars to the other eye, such that when properly fused, the combined binocular collinear length (nine elements) exceeded the critical length. No collinear search impairment was observed, implying that collinear information before binocular fusion shaped participants' search behavior, although contour extension from the other eye after binocular fusion enhanced the effect of collinearity on attention. Our results suggest that attention interacts with perceptual grouping as early as V1.

  2. MC148 encoded by human molluscum contagiosum poxvirus is an antagonist for human but not murine CCR8

    DEFF Research Database (Denmark)

    Lüttichau, H R; Gerstoft, J; Schwartz, T W

    2001-01-01

    The viral CC chemokines MC148, encoded by the poxvirus molluscum contagiosum, and viral macrophage inflammatory protein (vMIP)-I and vMIP-II, encoded by human herpesvirus 8, were probed on the murine CC receptor (CCR) 8 in parallel with human CCR8. In calcium mobilization assays, vMIP-I acted...... as a high-affinity agonist, whereas vMIP-II acted as a low-affinity antagonist on the murine CCR8 as well as the human CCR8. MC148 was found to bind and block responses through the human CCR8 with high affinity, but surprisingly MC148 was unable to bind and block responses through the murine CCR8. Because...

  3. Selective chemokine receptor usage by central nervous system myeloid cells in CCR2-red fluorescent protein knock-in mice.

    Directory of Open Access Journals (Sweden)

    Noah Saederup

    2010-10-01

    Full Text Available Monocyte subpopulations distinguished by differential expression of chemokine receptors CCR2 and CX3CR1 are difficult to track in vivo, partly due to lack of CCR2 reagents.We created CCR2-red fluorescent protein (RFP knock-in mice and crossed them with CX3CR1-GFP mice to investigate monocyte subset trafficking. In mice with experimental autoimmune encephalomyelitis, CCR2 was critical for efficient intrathecal accumulation and localization of Ly6C(hi/CCR2(hi monocytes. Surprisingly, neutrophils, not Ly6C(lo monocytes, largely replaced Ly6C(hi cells in the central nervous system of these mice. CCR2-RFP expression allowed the first unequivocal distinction between infiltrating monocytes/macrophages from resident microglia.These results refine the concept of monocyte subsets, provide mechanistic insight about monocyte entry into the central nervous system, and present a novel model for imaging and quantifying inflammatory myeloid populations.

  4. CD4-binding site alterations in CCR5-using HIV-1 envelopes influencing gp120-CD4 interactions and fusogenicity

    International Nuclear Information System (INIS)

    Sterjovski, Jasminka; Churchill, Melissa J.; Roche, Michael; Ellett, Anne; Farrugia, William; Wesselingh, Steven L.; Cunningham, Anthony L.; Ramsland, Paul A.; Gorry, Paul R.

    2011-01-01

    CD4-binding site (CD4bs) alterations in gp120 contribute to different pathophysiological phenotypes of CCR5-using (R5) HIV-1 strains, but the potential structural basis is unknown. Here, we characterized functionally diverse R5 envelope (Env) clones (n = 16) to elucidate potential structural alterations within the gp120 CD4bs that influence Env function. Initially, we showed that the magnitude of gp120-CD4-binding correlates with increased fusogenicity and reduced CD4 dependence. Analysis of three-dimensional gp120 structural models revealed two CD4bs variants, D279 and N362, that were associated with reduced CD4 dependence. Further structural analysis showed that a wider aperture of the predicted CD4bs cavity, as constrained by the inner-most atoms at the gp120 V1V2 stem and the V5 loop, was associated with amino acid alterations within V5 and correlated with increased gp120-CD4 binding and increased fusogenicity. Our results provide evidence that the gp120 V5 loop may alter CD4bs conformation and contribute to increased gp120-CD4 interactions and Env fusogenicity.

  5. Distribution of the CCR5delta32 allele (gene variant CCR5) in Rondônia, Western Amazonian region, Brazil

    Science.gov (United States)

    de Farias, Josileide Duarte; Santos, Marlene Guimarães; de França, Andonai Krauze; Delani, Daniel; Tada, Mauro Shugiro; Casseb, Almeida Andrade; Simões, Aguinaldo Luiz; Engracia, Vera

    2012-01-01

    Since around 1723, on the occasion of its initial colonization by Europeans, Rondonia has received successive waves of immigrants. This has been further swelled by individuals from northeastern Brazil, who began entering at the beginning of the twentieth century. The ethnic composition varies across the state according to the various sites of settlement of each wave of immigrants. We analyzed the frequency of the CCR5Δ32 allele of the CCR5 chemokine receptor, which is considered a Caucasian marker, in five sample sets from the population. Four were collected in Porto Velho, the state capital and the site of several waves of migration. Of these, two, from the Hospital de Base were comprised of HB Mothers and HB Newborns presenting allele frequencies of 3.5% and 3.1%, respectively, a third from the peri-urban neighborhoods of Candelária/Bate-Estaca (1.8%), whereas a fourth, from the Research Center on Tropical Medicine/CEPEM (0.6%), was composed of malaria patients under treament. The fifth sample (3.4%) came from the inland Quilombola village of Pedras Negras. Two homozygous individuals (CCR5Δ32/CCR5Δ32) were detected among the HB Mother samples. The frequency of this allele was heterogeneous and higher where the European inflow was more pronounced. The presence of the allele in Pedras Negras revealed European miscegenation in a community largely comprising Quilombolas. PMID:22481870

  6. CCR5 gene polymorphism is a genetic risk factor for radiographic severity of rheumatoid arthritis.

    Science.gov (United States)

    Han, S W; Sa, K H; Kim, S I; Lee, S I; Park, Y W; Lee, S S; Yoo, W H; Soe, J S; Nam, E J; Lee, J; Park, J Y; Kang, Y M

    2012-11-01

    The chemokine receptor [C-C chemokine receptor 5 (CCR5)] is expressed on diverse immune effecter cells and has been implicated in the pathogenesis of rheumatoid arthritis (RA). This study sought to determine whether single-nucleotide polymorphisms (SNPs) in the CCR5 gene and their haplotypes were associated with susceptibility to and severity of RA. Three hundred fifty-seven patients with RA and 383 healthy unrelated controls were recruited. Using a pyrosequencing assay, we examined four polymorphisms -1118 CTAT(ins) (/del) (rs10577983), 303 A>G (rs1799987), 927 C>T (rs1800024), and 4838 G>T (rs1800874) of the CCR5 gene, which were distributed over the promoter region as well as the 5' and 3' untranslated regions. No significant difference in the genotype, allele, and haplotype frequencies of the four selected SNPs was observed between RA patients and controls. CCR5 polymorphisms of -1118 CTAT(del) (P = 0.012; corrected P = 0.048) and 303 A>G (P = 0.012; corrected P = 0.048) showed a significant association with radiographic severity in a recessive model, and, as a result of multivariate logistic regression analysis, were found to be an independent predictor of radiographic severity. When we separated the erosion score from the total Sharp score, the statistical significance of CCR5 polymorphisms showed an increase; -1118 CTAT(ins) (/del) (P = 0.007; corrected P = 0.028) and 303 A>G (P = 0.007; corrected P = 0.028). Neither SNPs nor haplotypes of the CCR5 gene showed a significant association with joint space narrowing score. These results indicate that genetic polymorphisms of CCR5 are an independent risk factor for radiographic severity denoted by modified Sharp score, particularly joint erosion in RA. © 2012 John Wiley & Sons A/S.

  7. Exacerbation of Facial Motoneuron Loss after Facial Nerve Axotomy in CCR3-Deficient Mice

    Directory of Open Access Journals (Sweden)

    Derek A Wainwright

    2009-11-01

    Full Text Available We have previously demonstrated a neuroprotective mechanism of FMN (facial motoneuron survival after facial nerve axotomy that is dependent on CD4+ Th2 cell interaction with peripheral antigen-presenting cells, as well as CNS (central nervous system-resident microglia. PACAP (pituitary adenylate cyclase-activating polypeptide is expressed by injured FMN and increases Th2-associated chemokine expression in cultured murine microglia. Collectively, these results suggest a model involving CD4+ Th2 cell migration to the facial motor nucleus after injury via microglial expression of Th2-associated chemokines. However, to respond to Th2-associated chemokines, Th2 cells must express the appropriate Th2-associated chemokine receptors. In the present study, we tested the hypothesis that Th2-associated chemokine receptors increase in the facial motor nucleus after facial nerve axotomy at timepoints consistent with significant T-cell infiltration. Microarray analysis of Th2-associated chemokine receptors was followed up with real-time PCR for CCR3, which indicated that facial nerve injury increases CCR3 mRNA levels in mouse facial motor nucleus. Unexpectedly, quantitative- and co-immunofluorescence revealed increased CCR3 expression localizing to FMN in the facial motor nucleus after facial nerve axotomy. Compared with WT (wild-type, a significant decrease in FMN survival 4 weeks after axotomy was observed in CCR3–/– mice. Additionally, compared with WT, a significant decrease in FMN survival 4 weeks after axotomy was observed in Rag2 –/– (recombination activating gene-2-deficient mice adoptively transferred CD4+ T-cells isolated from CCR3–/– mice, but not in CCR3–/– mice adoptively transferred CD4+ T-cells derived from WT mice. These results provide a basis for further investigation into the co-operation between CD4+ T-cell- and CCR3-mediated neuroprotection after FMN injury.

  8. CCR5 controls immune and metabolic functions during Toxoplasma gondii infection.

    Directory of Open Access Journals (Sweden)

    Giuliano Bonfá

    Full Text Available CCR5, an important receptor related to cell recruitment and inflammation, is expressed during experimental Toxoplasma gondii infection. However, its role in the immunopathology of toxoplasmosis is not clearly defined yet. Thus, we inoculated WT and CCR5(-/- mice with a sub lethal dose of the parasite by oral route. CCR5(-/- mice were extremely susceptible to infection, presenting higher parasite load and lower tissue expression of IL-12p40, IFN-γ, TNF, IL-6, iNOS, Foxp3, T-bet, GATA-3 and PPARα. Although both groups presented inflammation in the liver with prominent neutrophil infiltration, CCR5(-/- mice had extensive tissue damage with hepatocyte vacuolization, steatosis, elevated serum triglycerides and transaminases. PPARα agonist Gemfibrozil improved the vacuolization but did not rescue CCR5(-/- infected mice from high serum triglycerides levels and enhanced mortality. We also found intense inflammation in the ileum of CCR5(-/- infected mice, with epithelial ulceration, augmented CD4 and decreased frequency of NK cells in the gut lamina propria. Most interestingly, these findings were accompanied by an outstanding accumulation of neutrophils in the ileum, which seemed to be involved in the gut immunopathology, once the depletion of these cells was accompanied by reduced local damage. Altogether, these data demonstrated that CCR5 is essential to the control of T. gondii infection and to maintain the metabolic, hepatic and intestinal integrity. These findings add novel information on the disease pathogenesis and may be relevant for directing future approaches to the treatment of multi-deregulated diseases.

  9. CCR2 V64I polymorphism in rifampicin resistant tuberculosis patients in Moewardi General Hospital Surakarta, Indonesia

    Science.gov (United States)

    Marwoto; Agung Prasetyo, Afiono; Reviono; Suradi

    2018-05-01

    CC chemokine receptor-2 (CCR2) play important roles in inflammation. The CCR2 V64I polymorphism already reported associated with many diseases; however, the association of CCR2 V64I polymorphism with tuberculosis is still unknown. Also, there is no report about the presentation of CCR2 V64I polymorphisms in Indonesian tuberculosis patients with rifampicin-mono resistant status has ever been published, to the best of our knowledge. This study evaluated the presence of CCR2 V64I polymorphisms in Javanese rifampicin-mono resistant tuberculosis patients. In an ongoing molecular epidemiology study of human genomic polymorphisms and infection, 51 Javanese rifampicin-mono resistant tuberculosis patients in Dr. Moewardi General Hospital in Surakarta were enrolled in the study. The blood samples were aliquoted and fractionated. The nucleic acids were extracted from all blood samples and subjected to the CCR2 V64I polymorphisms detection by a polymerase chain reaction-sequence-specific primer (PCR-SSP) technique. PCR products were analyzed in 3% agarose. CCR2 64V and 64I homozygote were found in 23.5% (12/51) and 23.5% (12/51) blood samples, respectively. The CCR2 VI genotype was found in 52.9% (27/51) blood samples. The CCR2 VI genotype was found predominant in Javanese rifampicin-mono resistant tuberculosis patients and may have anassociation with the clinical progression.

  10. Synthesis and evaluation of 99mTc/99Tc-MAG3-biotin conjugates for antibody pretargeting strategies

    International Nuclear Information System (INIS)

    Gog, Frank B. van; Visser, Gerard W.M.; Gowrising, Radjish W.A.; Snow, Gordon B.; Dongen, Guus A.M.S. van

    1998-01-01

    Four 99m Tc-MAG3-biotin conjugates were synthesized to determine their potential use in antibody pretargeting strategies for radioimmunoscintigraphy (RIS). To use these 99m Tc-MAG3-biotin conjugates as model compounds for 186 Re-MAG3-biotin conjugates for radioimmunotherapy (RIT), nanomolar amounts of 99 Tc were added as carrier to 99m Tc. The biotin derivatives used for the preparation of the conjugates - biocytin, biotin hydrazide, biotinyl-piperazine, and biotinyl-diaminosuccinic acid - differed at the site that is regarded to be susceptible to hydrolysis by biotinidase present in human plasma. All four conjugates were produced with high radiochemical purity, were stable in PBS, and demonstrated full binding capacity to streptavidin. The 99m Tc/ 99 Tc-MAG3-labeled biotinyl-piperazine and biotinyl-diaminosuccinic acid conjugates were stable in mouse as well as human plasma, whereas the corresponding biocytin and biotin hydrazide conjugates were rapidly degraded. The biodistribution in nude mice at 30 min after injection was similar for all conjugates, and a rapid blood clearance and high intestinal excretion were both observed. It is concluded that the metabolic routing of a conjugate containing biotin and MAG3 is dominated by these two moieties. For this reason, MAG3-biotin conjugates do not seem suited for pretargeted RIT, for which quantitative and fast renal excretion is a prerequisite to minimize radiation toxicity. However, in a pretargeted RIS approach the 99m Tc-MAG3-biotin conjugates might have potential

  11. [99mTc]MAG3-mannosyl-dextran: a receptor-binding radiopharmaceutical for sentinel node detection

    International Nuclear Information System (INIS)

    Vera, David R.; Wallace, Anne M.; Hoh, Carl K.

    2001-01-01

    Technetium-99m-labeled benzoyl-mercaptoacetylglycylglycyl-glycine-mannosyl-dextran ([ 99m Tc]MAG 3 -mannosyl-dextran) is a receptor-binding radiotracer that binds to mannose-binding protein, a receptor expressed by reticuloendothelial tissue. This agent is composed of a 10.5-kilodalton molecule of dextran and multiple units of mannose, and benzoyl-mercaptoacetylglycylglycyl-glycine (BzMAG 3 ). The tetraflorophenol-activated ester of BzMAG 3 and the imidate of thiomannose were used to covalently attach BzMAG 3 and mannose to an amino-terminated conjugate of dextran. This yielded a 19-kilodalton macromolecule consisting of 3 BzMAG 3 and 21 mannose units per dextran. Dynamic light scattering was used to measure a mean diameter of 5.5 nanometers for BzMAG 3 -mannosyl-dextran and 0.28 microns for filtered Tc-99m sulfur colloid. A preliminary sentinel node detection study employing right fore and hind footpad injections of [ 99m Tc]MAG 3 -mannosyl-dextran and left fore and hind footpad injections of filtered Tc-99m sulfur colloid demonstrated greater sentinel lymph node uptake by the receptor-binding agent

  12. Use of 99mTc mercaptoacetyltriglycine (MAG3) for detection of renal lesions after ESWL

    International Nuclear Information System (INIS)

    Schaub, T.; Witsch, U.; El-Damanhoury, H.; Naegele-Woehrle, B.; Hahn, K.

    1992-01-01

    Extracorporeal shock wave lithotripsy (ESWL) has become the treatment of choice for urinary calculi. 117 patients were studied prospectively with 99m Tc Mercaptoacetyltriglycine (MAG3) before and after ESWL. 79 (66%) of the 119 kidneys treated had abnormal findings. Of these 63/119 (53%) had abnormal scans. 41 (65%) had focal lesions with a delayed intrarenal transport. The remaining 22 had a diffuse delay of intrarenal transport. A loss of relative renal function of 3% and more compared to the pretreatment values was observed in 50/119 (42%) patients. 99m Tc MAG3 should be done routinely together with radiologic tests (CT or MRI) before and after ESWL to select the patients at risk for post ESWL hypertension. (orig.) [de

  13. Acetazolamide assisted Tc-99m MAG3 renography to assess renal blood flow reserve

    International Nuclear Information System (INIS)

    Horita, Yoshio; Hayashida, Kohei; Fukuchi, Kazuki

    2003-01-01

    The present study examines whether or not baseline and acetazolamide (ACZ) Tc-99m MAG3 renography can assess renal blood flow reserve. Renography proceeded for 50 min after sequential injections of 370 MBq Tc-99m MAG3 for baseline renography and 10 min after a 1,000 mg injection of ACZ for ACZ renography. Effective renal plasma flow of renal cortex (cERPF) in each kidney and the percentage change in cERPF of those parameters (ΔERPF) were obtained before and after the administration of ACZ in 10 subjects without hypertension or diabetes (normal group), in 10 with essential hypertension (hypertensive group) and in 10 who had Type 2 diabetes with hypertension (diabetic group). A placebo test was performed in the 10 without hypertension or diabetes using distilled water instead of ACZ (placebo group). The placebo test performed in the 10 without hypertension or diabetes using distilled water instead of ACZ indicated that the parameter variance between the two types of renogram was below 3.2%. The cERPF of baseline and ACZ Tc-99m MAG3 renography and ΔERPF in the normal, hypertensive and diabetic groups were 89±10 and 110±10 ml/min, 89±14 and 117±22 ml/min, 100±23 and 112±23 ml/min, respectively, and 24.5±13.5%, 26.0±9.7% and 12.3±11.1%, respectively. The difference in the cERPF value was significant in the normal and hypertensive groups whereas this did not change in the diabetic group before or after ACZ administration. We suggested that the ΔERPF determined by baseline and ACZ Tc-99m MAG3 renography is a useful parameter for assessing renal blood flow reserve. (author)

  14. MAG3 diuresis renography and output efficiency measurement in renal transplant patients

    International Nuclear Information System (INIS)

    Spicer, T.; Gruenewald, S.; Chi, K.K.; Larcos, G.; Farlow, D.; Choong, K.; Chapman, J.

    1997-01-01

    Full text: Urinary tract obstruction following renal transplantation often presents a diagnostic dilemma, as some patients with equivocal investigations subsequently show improvement following stenting. The purposes of this study were to (1) establish a normal range of renal output efficiency (ROE) in transplants, and (2) assess the usefulness of MAG3 diuresis renography and ROE in suspected allograft obstruction. Twenty-two renal transplant patients with stable function and no evidence of hydronephrosis on serial ultrasound had a diuretic MAG3 scan with calculation of ROE. Three patients with proven graft obstruction underwent the same scanning procedure. Methodology was as follows: (1) 60 MBq of 99m Tc-DTPA GFR was performed (single injection-dual blood sample method); (2) patients were then prehydrated with either oral or IV fluid; (3) 10 min prior to scanning, intravenous Frusemide 20-80 mg (dose depending on renal function) was injected, and then (4) 200 MBq of MAG3 for a 20 min scan. The studies were then qualitatively and quantitatively reviewed to assess uptake and excretion, and the ROE was calculated. The mean ROE for the twenty-two normal renal transplant patients was 85.7% ± 4.1% (range 78 - 90%). Technetium-99m-DTPA GFR was 55.5 mL/min/1.73m 2 (range 27 to 83). The MAG3 scans in the three obstructed patients were equivocal for obstruction but the ROE values of 59%, 68% and 75% were more than 2.5 standard deviations below our calculated normal mean. The 99m Tc-DTPA GFRs were 61,17 and 57 mL/min/1.73m 2 , respectively. Thus, in normal grafts the ROE should exceed 78 per cent. Our data suggest that ROE may be a useful addition to standard scintigraphic parameters in diagnosis of graft obstruction

  15. The development and characterization of Tc-99m mecaptoacetyltriglycine (MAG3)

    International Nuclear Information System (INIS)

    Taylor, A. Jr.; Eshima, D.

    1990-01-01

    I-131 orth-iodohippuric (OIH) acid is a widely used renal radiopharmaceutical but it is limited due to the suboptimal imaging properties of the I-131 radionuclide and the relatively high radiation dose. Recent work has focused on the development of Tc-99m renal tubular function agents which would utilize the optimal radionuclidic properties and availability of Tc-99m, provide comparable clinical information to that obtained with OIH and allow the evaluation of renal perfusion. The triamide mercaptide (N 3 S) donor ligand system has yielded the most promising Tc-99m tubular function agent to date. Tc-99m mercaptoacetyltriglycine MAG 3 does not enter the red blood cell. A simple kit formulation has been developed which yields a stable Tc-99m MAG 3 complex in high radiochemical purity. Studies in normal volunteers and patients indicate that Tc-99m MAG 3 is an excellent Tc-99m renal tubular agent but its clearance is only 50-60% that of OIH. 42 refs., 2 tabs., 2 figs

  16. Magnetic Microbead Affinity Selection Screening (MagMass) of Botanical Extracts for Inhibitors of 15-Lipoxygenase

    Science.gov (United States)

    Rush, Michael D.; Walker, Elisabeth M.; Burton, Tristesse; van Breemen, Richard B.

    2016-01-01

    To expedite the identification of active natural products in complex mixtures such as botanical extracts, a Magnetic Microbead Affinity Selection Screening (MagMASS) procedure was developed. This technique utilizes target proteins immobilized on magnetic beads for rapid bioaffinity isolation of ligands from complex mixtures. A MagMASS method was developed and validated for 15-lipoxygenase. As a proof of concept, several North American prairie plants used medicinally by Native Americans were extracted with MeOH and screened. A hit from an extract of Proserpinaca palustris, also known as mermaid weed, was flagged for further characterization using high-resolution tandem mass spectrometry, dereplication, and identification using XCMS online. Through the application of high-resolution product ion tandem mass spectrometry, comparison with natural product databases and confirmation using standards, the hit was identified as quercitrin, which is a known inhibitor of 15-lipoxygenase. The overall workflow of MagMASS is faster and more amendable to automation than alternative methods designed for screening botanical extracts or complex mixtures of combinatorial libraries. PMID:27802026

  17. 92R Monoclonal Antibody Inhibits Human CCR9+ Leukemia Cells Growth in NSG Mice Xenografts.

    Science.gov (United States)

    Somovilla-Crespo, Beatriz; Martín Monzón, Maria Teresa; Vela, Maria; Corraliza-Gorjón, Isabel; Santamaria, Silvia; Garcia-Sanz, Jose A; Kremer, Leonor

    2018-01-01

    CCR9 is as an interesting target for the treatment of human CCR9 + -T cell acute lymphoblastic leukemia, since its expression is limited to immature cells in the thymus, infiltrating leukocytes in the small intestine and a small fraction of mature circulating T lymphocytes. 92R, a new mouse mAb (IgG2a isotype), was raised using the A-isoform of hCCR9 as immunogen. Its initial characterization demonstrates that binds with high affinity to the CCR9 N-terminal domain, competing with the previously described 91R mAb for receptor binding. 92R inhibits human CCR9 + tumor growth in T and B-cell deficient Rag2 -/- mice. In vitro assays suggested complement-dependent cytotoxicity and antibody-dependent cell-mediated cytotoxicity as possible in vivo mechanisms of action. Unexpectedly, 92R strongly inhibited tumor growth also in a model with compromised NK and complement activities, suggesting that other mechanisms, including phagocytosis or apoptosis, might also be playing a role on 92R-mediated tumor elimination. Taken together, these data contribute to strengthen the hypothesis of the immune system's opportunistic nature.

  18. Inhibition of HIV-1 infection by synthetic peptides derived CCR5 fragments

    International Nuclear Information System (INIS)

    Imai, Masaki; Baranyi, Lajos; Okada, Noriko; Okada, Hidechika

    2007-01-01

    HIV-1 infection requires interaction of viral envelope protein gp160 with CD4 and a chemokine receptor, CCR5 or CXCR4 as entry coreceptor. We designed HIV-inhibitory peptides targeted to CCR5 using a novel computer program (ANTIS), which searched all possible sense-antisense amino acid pairs between proteins. Seven AHBs were found in CCR5 receptor. All AHB peptides were synthesized and tested for their ability to prevent HIV-1 infection to human T cells. A peptide fragment (LC5) which is a part of the CCR5 receptor corresponding to the loop between the fifth and sixth transmembrane regions (amino acids 222-240) proved to inhibit HIV-1 IIIB infection of MT-4 cells. Interaction of these antisense peptides could be involved in sustaining HIV-1 infectivity. LC5 effectively indicated dose-dependent manner, and the suppression was enhanced additively by T20 peptide, which inhibits infection in vitro by disrupting the gp41 conformational changes necessary for membrane fusion. Thus, these results indicate that CCR5-derived AHB peptides could provide a useful tool to define the mechanism(s) of HIV infection, and may provide insight which will contribute to the development of an anti-HIV-1 reagent

  19. CCL3L1 copy number, CCR5 genotype and susceptibility to tuberculosis.

    Science.gov (United States)

    Carpenter, Danielle; Taype, Carmen; Goulding, Jon; Levin, Mike; Eley, Brian; Anderson, Suzanne; Shaw, Marie-Anne; Armour, John A L

    2014-01-09

    Tuberculosis is a major infectious disease and functional studies have provided evidence that both the chemokine MIP-1α and its receptor CCR5 play a role in susceptibility to TB. Thus by measuring copy number variation of CCL3L1, one of the genes that encode MIP-1α, and genotyping a functional promoter polymorphism -2459A > G in CCR5 (rs1799987) we investigate the influence of MIP-1α and CCR5, independently and combined, in susceptibility to clinically active TB in three populations, a Peruvian population (n = 1132), a !Xhosa population (n = 605) and a South African Coloured population (n = 221). The three populations include patients with clinically diagnosed pulmonary TB, as well as other, less prevalent forms of extrapulmonary TB. Copy number of CCL3L1 was measured using the paralogue ratio test and exhibited ranges between 0-6 copies per diploid genome (pdg) in Peru, between 0-12 pdg in !Xhosa samples and between 0-10 pdg in South African Coloured samples. The CCR5 promoter polymorphism was observed to differ significantly in allele frequency between populations (*A; Peru f = 0.67, !Xhosa f = 0.38, Coloured f = 0.48). The case-control association studies performed however find, surprisingly, no evidence for an influence of variation in genes coding for MIP-1α or CCR5 individually or together in susceptibility to clinically active TB in these populations.

  20. Design of a Base Station for MEMS CCR Localization in an Optical Sensor Network

    Directory of Open Access Journals (Sweden)

    Chan Gook Park

    2014-05-01

    Full Text Available This paper introduces a design and implementation of a base station, capable of positioning sensor nodes using an optical scheme. The base station consists of a pulse laser module, optical detectors and beam splitter, which are mounted on a rotation-stage, and a Time to Digital Converter (TDC. The optical pulse signal transmitted to the sensor node with a Corner Cube Retro-reflector (CCR is reflected to the base station, and the Time of Flight (ToF data can be obtained from the two detectors. With the angle and flight time data, the position of the sensor node can be calculated. The performance of the system is evaluated by using a commercial CCR. The sensor nodes are placed at different angles from the base station and scanned using the laser. We analyze the node position error caused by the rotation and propose error compensation methods, namely the outlier sample exception and decreasing the confidence factor steadily using the recursive least square (RLS methods. Based on the commercial CCR results, the MEMS CCR is also tested to demonstrate the compatibility between the base station and the proposed methods. The result shows that the localization performance of the system can be enhanced with the proposed compensation method using the MEMS CCR.

  1. Colorectal carcinoma metastases: Detection with In-111-labeled monoclonal antibody CCR 086

    International Nuclear Information System (INIS)

    Abdel-Nabi, H.H.; Levine, G.; Lamki, L.M.; Murray, J.L.; Tauxe, W.N.; Shah, A.N.; Patt, Y.Z.; Doerr, R.J.; Klein, H.A.; Gona, J.

    1990-01-01

    A phase I/II clinical trial with indium-111-labeled antimucin murine monoclonal antibody (MoAb) CCR 086 was conducted. Seventeen patients with histologically proved colorectal carcinoma and known metastatic disease underwent external scintigraphy after administration of 5.5 mCi (203.5 MBq) of In-111 CCR 086 at doses of 5 and 20 mg. Of 25 known lesions, 17 were detected (sensitivity, 68%). The smallest detected lesion in the lung was 1 cm and in the liver was 1.5 cm. The serum half-life of In-111-labeled CCR 086 MoAb was approximately 64 hours. The formation of human antimouse antibody (HAMA) was detected in the serum of four of five patients who received 20 mg of MoAb. No HAMAs were detected in four patients receiving 5 mg of MoAb. No side effects were encountered. Because of effective detection of liver and lung metastases with lower doses (5-20 mg) of CCR 086 conjugated with In-111, further investigations are warranted to assess clinical and therapeutic potentials of CCR 086 in the management of colorectal cancer

  2. Design of a base station for MEMS CCR localization in an optical sensor network.

    Science.gov (United States)

    Park, Chan Gook; Jeon, Hyun Cheol; Kim, Hyoun Jin; Kim, Jae Yoon

    2014-05-08

    This paper introduces a design and implementation of a base station, capable of positioning sensor nodes using an optical scheme. The base station consists of a pulse laser module, optical detectors and beam splitter, which are mounted on a rotation-stage, and a Time to Digital Converter (TDC). The optical pulse signal transmitted to the sensor node with a Corner Cube Retro-reflector (CCR) is reflected to the base station, and the Time of Flight (ToF) data can be obtained from the two detectors. With the angle and flight time data, the position of the sensor node can be calculated. The performance of the system is evaluated by using a commercial CCR. The sensor nodes are placed at different angles from the base station and scanned using the laser. We analyze the node position error caused by the rotation and propose error compensation methods, namely the outlier sample exception and decreasing the confidence factor steadily using the recursive least square (RLS) methods. Based on the commercial CCR results, the MEMS CCR is also tested to demonstrate the compatibility between the base station and the proposed methods. The result shows that the localization performance of the system can be enhanced with the proposed compensation method using the MEMS CCR.

  3. Influence of CCR7 ligand DNA preexposure on the magnitude and duration of immunity

    International Nuclear Information System (INIS)

    Lee, Yunsang; Seong, Kug Eo; Rouse, Richard J.D.; Rouse, Barry T.

    2003-01-01

    The CC chemokine receptor (CCR) 7 ligands CCL21 and CCL19 were recently described as essential elements for establishing the microenvironment needed to initiate optimal immune responses in secondary lymphoid tissues. In the present study we have kinetically investigated the primary responses of naive DO11.10 TCR-transgenic CD4+ T cells (OVA323-339 peptide specific) adoptively transferred into normal BALB/c mice given plasmid DNA encoding CCR7 ligands. The primary responses of CD4+ Tg-T cells in CCR7 ligand DNA recipients occurred more promptly, reaching levels higher than those observed in vector controls. In line with enhanced specific immunity, the T-cell population in CCR7 ligand recipients underwent more in vivo cell division following Ag stimulation, and a higher percentage of Ag-specific T cells expressed an activation phenotype. Moreover, the enhanced primary responses of naive CD4+ T cells appeared to act via affects on migration and maturation of CD11c+ dendritic cells in the draining lymph nodes. In addition following mucosal challenge of herpes simplex virus-immune mice with virus, those that had received CCL21 or CCL19 during priming contained a higher frequency of responding CD4 T cells in lymph nodes and the site of infection. Moreover, CCL21- and CCL19-treated mice showed less severe disease and better survival following challenge. Our results are discussed in terms of the relevance of CCR7 ligand preimmunization to improve vaccine

  4. Polarized expression of the GFP-tagged rat V(1a) vasopressin receptor.

    Science.gov (United States)

    Campos, D M; Reyes, C E; Sarmiento, J; Navarro, J; González, C B

    2001-11-30

    We investigated the targeting of the V(1a) receptor fused with the green fluorescence protein (V(1a)R-GFP) in polarized MDCK cells. Cells expressing V(1a)R-GFP displayed binding to vasopressin (AVP) and AVP-induced calcium responses, similar to cells expressing the wild-type V1a receptor. Interestingly, as with the wild-type V(1a)R, V(1a)R-GFP is preferentially distributed in the basolateral side of MDCK cells as monitored by confocal microscopy. Furthermore, AVP induced internalization of GFP-tagged receptors. Therefore, the GFP-tagged V(1a) receptor retains all the sorting signals of the wild-type receptor and offers an excellent system to elucidate the mechanisms of cell trafficking of V(1a) receptors.

  5. Murine macrophage response from peritoneal cavity requires signals mediated by chemokine receptor CCR-2 during Staphylococcus aureus infection.

    Science.gov (United States)

    Nandi, Ajeya; Bishayi, Biswadev

    2016-02-01

    C-C chemokine receptor-2 (CCR-2) is a cognate receptor for monocyte chemotactic protein-1 (MCP-1), and recent studies revealed that MCP-1-CCR-2 signaling is involved in several inflammatory diseases characterized by macrophage infiltration. Currently, there is no study on the involvement of CCR-2 in the killing of S. aureus by macrophages of Swiss albino mice, and its substantial role in host defense against S. aureus infection in murine macrophages is still unclear. Therefore, the present study was aimed to investigate the functional and interactive role of CCR-2 and MCP-1 in regulating peritoneal macrophage responses with respect to acute S. aureus infection. We found that phagocytosis of S. aureus can serve as an important stimulus for MCP-1 production by peritoneal macrophages, which is dependent directly or indirectly on cytokines, reactive oxygen species and nitric oxide. Neutralization of CCR-2 in macrophages leads to increased production of IL-10 and decreased production of IFN-γ and IL-6. In CCR-2 blocked macrophages, pretreatment with specific blocker of NF-κB or p38-MAPK causes elevation in MCP-1 level and subsequent downregulation of CCR-2 itself. We speculate that CCR-2 is involved in S. aureus-induced MCP-1 production via NF-κB or p38-MAPK signaling. We also hypothesized that unnaturally high level of MCP-1 that build up upon CCR-2 neutralization might allow promiscuous binding to one or more other chemokine receptors, a situation that would not occur in CCR-2 non-neutralized condition. This may be the plausible explanation for such observed Th-2 response in CCR-2 blocked macrophages infected with S. aureus in the present study.

  6. Renal scintigraphy in the 21st Century 99m Tc-MAG3 with zero time injection of furosemide (MAG3-F0): a fast and easy protocol, one for all indications. Part 1. Introduction

    International Nuclear Information System (INIS)

    Sfakianakis, G.N.

    2007-01-01

    In this work the MAG 3 -F 0 protocol is presented. Did you ever want to have one fast and easy protocol for Scintirenography?. The same for all indications. (Parenchymal and Drainage ). Irrespective of the age of the patient, the degree of impairment of the renal function, the general clinical condition of the patient, and obtain also information about prognosis absolutely safely and reproducibly. This is the MAG 3 -F 0 protocol. (Author)

  7. A case study presentation: The MAG3 captopril renal scan, which side are you on ?

    International Nuclear Information System (INIS)

    Richards, A.

    1998-01-01

    Full text: A 68-year-old woman with widespread vascular disease presented to the Nuclear Medicine Department with severe hypertension, (a blood pressure of 200/160 supine), a known small right kidney, and a large abdominal aortic aneurysm. A baseline renal scan was performed with IV administration of 300 MBq of 99m Tc-labelled MAG3. A normal left kidney was demonstrated, with a Grade 0 renogram pattern. The right kidney was non visualised and non functioning. The patient was then administered orally with 25 mg of A.C.E. inhibitor captopril and her blood pressure fell by greater than 100 mm Hg. A second MAG3 Renal Scan was performed. The finding conflicted with results of a Renal Artery Angiogram and Renal Artery Doppler Ultrasound, both demonstrating a normal left renal artery. A repeat MAG3 Renal scan with captopril challenge was performed. Differential diagnosis included: 1.Left sided microvascular disease; 2. A functioning though very ischaemic right kidney that was producing renin, suggested by contrast opacification of the right renal cortex on CT; or 3. A false negative renal artery angiogram, with non-visualisation of an arterial stenosis caused by thrombus or compression of the left renal artery by the abdominal aortic aneurysm. Subsequent Renal Vein Renin Sampling measured left renal vein renin activity at 4.50,μg/L/h, (compared with 4.80μg/L/h in the IVC). Right renal vein renin activity was 13.20μg/L/h. This lateralization of renin secretion to the right side with suppression of left sided secretion suggested that the renovascular hypertension was caused by the right kidney. This was a very unusual result, as the MAG3 captopril renal scan had incorrectly and strongly suggested a left sided origin to the renovascular hypertension. In addition, the right kidney not seen to accumulate MAG3 was in fact functioning sufficiently to produce renin. It is hypothesized that the left kidney had adjusted to allow normal function only at very high circulating

  8. CCR5 antibodies HGS004 and HGS101 preferentially inhibit drug-bound CCR5 infection and restore drug sensitivity of Maraviroc-resistant HIV-1 in primary cells

    International Nuclear Information System (INIS)

    Latinovic, Olga; Reitz, Marvin; Le, Nhut M.; Foulke, James S.; Faetkenheuer, Gerd; Lehmann, Clara; Redfield, Robert R.; Heredia, Alonso

    2011-01-01

    R5 HIV-1 strains resistant to the CCR5 antagonist Maraviroc (MVC) can use drug-bound CCR5. We demonstrate that MVC-resistant HIV-1 exhibits delayed kinetics of coreceptor engagement and fusion during drug-bound versus free CCR5 infection of cell lines. Antibodies directed against the second extracellular loop (ECL2) of CCR5 had greater antiviral activity against MVC-bound compared to MVC-free CCR5 infection. However, in PBMCs, only ECL2 CCR5 antibodies HGS004 and HGS101, but not 2D7, inhibited infection by MVC resistant HIV-1 more potently with MVC-bound than with free CCR5. In addition, HGS004 and HGS101, but not 2D7, restored the antiviral activity of MVC against resistant virus in PBMCs. In flow cytometric studies, CCR5 binding by the HGS mAbs, but not by 2D7, was increased when PBMCs were treated with MVC, suggesting MVC increases exposure of the relevant epitope. Thus, HGS004 and HGS101 have antiviral mechanisms distinct from 2D7 and could help overcome MVC resistance.

  9. Evaluation of total renal function from 99mTc-MAG3 scintigraphy in children

    International Nuclear Information System (INIS)

    Andersson, L.G.; Bratteby, L.E.; Takalo, R.; Svensson, L.

    2002-01-01

    Aim: The aim of the present study was to evaluate the usefulness of dynamic scintigraphy in the assessment of total renal function in children. The Patlak slope of 99m Tc-MAG3 renography curves were compared to the plasma clearance values of 51Cr-EDTA. Material and methods: The study sample consisted of 53 boys and 33 girls with various nephrologic disorders, referred for routine clinical reasons. The median age of the subjects was 5.1 years (range 0.3 - 14.1 years). Imaging procedure. In supine position, the patient received a bolus injection of 1 MBq/kg, (minimum 10 MBq) 99m Tc-MAG3 and a posterior dynamic gamma camera registration was performed for 21 min using 1 frame per second during the first minute and thereafter 10 seconds frames. Data analysis. Time-activity curves were generated from manually drawn heart and renal regions of interest. The MAG3 uptake was calculated from the Patlak-Rutland plot of each kidney by linear curve fitting until the beginning of the excretory phase. A sum of the slope values was used as a measure of total renal MAG3 uptake. Cr-EDTA clearance. Glomerular filtration rate (GFR) was measured from the plasma clearance of 51 Cr-EDTA using single injection, multiple-sample technique. After intravenous injection of 51 Cr-EDTA (74 kBq/kg for children up to 7 years, 37 kBq/kg for children older than 7 years), blood samples were drawn at 5, 10, 15, 45, 60, 120 and 180 min for radioactivity measurement. The GFR was calculated according to Broechner-Mortensen and expressed in ml/min. Results: The absolute 51 Cr-EDTA clearance varied from 9 to 143 ml/min. There was a close linear relationship between 51 Cr-EDTA clearance and MAG3 uptake (Fig). The correlation coefficient was 0.90 and the regression equation (y=43.5 x + 664). Conclusions: In the present study, there was a good correlation between plasma clearance of 51 Cr-EDTA and the sum of the Patlak slopes. The regression equation can be utilised to transform the 99m Tc-MAG3 uptake to an

  10. Synthesis, formulation of nucleo-equipment and biological studies of the {sup 99m} Tc-MAG{sub 3}; Sintesis, formulacion de nucleo-equipos y estudios biologicos de la {sup 99m} Tc-MAG{sub 3}

    Energy Technology Data Exchange (ETDEWEB)

    Reyes H, L; Lezama C, J; Ferro F, G

    1991-10-15

    Technetium-99m-mercaptoacetyl glycylglycylglycine ({sup 99m}Tc-MAG{sub 3}) is introduced to replace o-iodohippurate (OIH) for renal function studies. In this paper we present the synthesis, labelling and biological evaluation of {sup 99m}Tc- MAG{sub 3} prepared in our laboratory. The precursor s-benzoyl-mercaptoacetyl glycyl glycylglycine (Bz-MAG{sub 3} ) was synthesized by condensation of glycylglycylglycine with chloroacetyl chloride to obtain chloroacetyl glycylglycylglycine and this product was condensate with sodium thiobenzoate. The Bz-MAG{sub 3} was characterized by IR and NMR. The labelling with {sup 99m}Tc was carried out at pH 9.0 using stannous chloride as a reducing agent with heating to boiling for 15 min. The benzoyl group is lost in this step, forming {sup 99m}Tc-MAG{sub 3} complex with radiochemical purity of 99%. The biodistribution properties were evaluated in mice and a rapid renal extraction was apparent at the 10 minutes value (51.65% of the injected dose). The radiotracer was administered to 5 patients showing a good biological behavior. Based on these results, the {sup 99m}Tc-MAG{sub 3} is expected to have widespread clinical utility in Mexico. (Author)

  11. Molecular interaction of a potent nonpeptide agonist with the chemokine receptor CCR8

    DEFF Research Database (Denmark)

    Jensen, Pia C; Nygaard, Rie; Thiele, Stefanie

    2007-01-01

    Most nonpeptide antagonists for CC-chemokine receptors share a common pharmacophore with a centrally located, positively charged amine that interacts with the highly conserved glutamic acid (Glu) located in position 6 of transmembrane helix VII (VII:06). We present a novel CCR8 nonpeptide agonist......, 8-[3-(2-methoxyphenoxy)benzyl]-1-phenethyl-1,3,8-triaza-spiro[4.5]decan-4-one (LMD-009), that also contains a centrally located, positively charged amine. LMD-009 selectively stimulated CCR8 among the 20 identified human chemokine receptors. It mediated chemotaxis, inositol phosphate accumulation......-binding pockets of CCR8 uncovered that the binding of LMD-009 and of four analogs [2-(1-(3-(2-methoxyphenoxy)benzyl)-4-hydroxypiperidin-4-yl)benzoic acid (LMD-584), N-ethyl-2-4-methoxybenzenesulfonamide (LMD-902), N-(1-(3-(2-methoxyphenoxy)benzyl)piperidin-4-yl)-2-phenyl-4-(pyrrolidin-1yl)butanamide (LMD-268...

  12. Diuresis renography; A simultaneous comparison between sup 131 I-hippuran and sup 99 Tc sup m -MAG sub 3

    Energy Technology Data Exchange (ETDEWEB)

    Hvid-Jacobsen, K.; Thomsen, H.S.; Nielsen, S.L. (Koebenhavns Amts Sygehus, Herlev (Denmark). Dept. of Nuclear Medicine)

    1990-01-01

    In 20 patients investigated for unilateral upper urinary tract obstruction diuresis renography was performed simultaneously with {sup 131}I-hippuran and {sup 99}Tc{sup m}-MAG{sub 3} using a gamma camera with dual isotope facilities. Furosemide was administered routinely 20 min after radionuclide injection. No significant differences were found in fractional share between the two kidneys, time to maximal activity, residual activity at 20 and 30 min, or rate of emptying after furosemide administration. The MAG{sub 3} curves showed, however, better counting statistics and on scintigrams with MAG{sub 3} more anatomic details (extent of dilation and site of obstruction) could be seen. It is concluded, that MAG{sub 3} is superior to hippuran in the evaluation of patients with possible unilateral upper urinary tract obstruction by diuresis renography. (orig.).

  13. The prognostic significance and relationship with body composition of CCR7-positive cells in colorectal cancer.

    Science.gov (United States)

    Malietzis, George; Lee, Gui Han; Bernardo, David; Blakemore, Alexandra I F; Knight, Stella C; Moorghen, Morgan; Al-Hassi, Hafid O; Jenkins, John T

    2015-07-01

    The host local immune response (LIR) to cancer is a determinant of cancer outcome. Regulation of this local response is largely achieved through chemokine synthesis from the tumor microenvironment such as C-Chemokine-Receptor-7 (CCR7). We examined the LIR measured as CCR7 expression, in colorectal cancers (CRC) and explored relationships with body composition (BC) and survival. A study of paraffin-embedded tissue specimens was carried out in 116 patients with non-metastatic CRC. CCR7 expression was determined by immunohistochemistry. Analysis of computer tomography scans was used to calculate BC parameters. Survival analyses and multivariate regression models were used. High CCR7(+) cell density within the tumor stroma and at the margin was significantly associated with increased age, the presence of lymphovascular invasion, higher tumor stage, lymph node metastasis, high Klintrup-Makinen immune score, and myosteatosis. High CCR7(+) cell density in the tumor margin was significantly associated with shorter disease-free (DFS) and overall survival (OS) (P < 0.001). This was also significantly associated with shorter survival in multivariate analysis (HR = 8.87; 95%CI [2.51-31.3]; P < 0.01 for OS and HR = 4.72; 95%CI (1.24-12.9); P = 0.02 for DFS). Our results suggest that a specific immune microenvironment may be associated with altered host's BC and tumor behavior, and that CCR7 may serve as a novel prognostic biomarker. © 2015 Wiley Periodicals, Inc.

  14. Advantages of MAG-STT Welding Process for Root Pass Welding in the Oil and Gas Industry

    Directory of Open Access Journals (Sweden)

    Pandzic Adi

    2016-02-01

    Full Text Available This paper describesthe basics of modern MAG-STT welding process and its advantages for root pass welding of construction steels in oil and gas industry. MAG-STT welding process was compared with competitive arc welding processes (SMAW and TIG, which are also used for root pass welding on pipes and plates. After experimental tests, the obtained results are analyzed and presented in this paper

  15. Can computed tomography volumetry of the renal cortex replace MAG3-scintigraphy in all patients for determining split renal function?

    Science.gov (United States)

    Houbois, Christian; Haneder, Stefan; Merkt, Martin; Morelli, John N; Schmidt, Matthias; Hellmich, Martin; Mueller, Roman-Ulrich; Wahba, Roger; Maintz, David; Puesken, Michael

    2018-06-01

    The current gold standard for determination of split renal function (SRF) is Tc-99m-mercapto-acetyltriglycin (MAG3) scintigraphy. Initial studies comparing MAG3-scintigraphy and CT-based renal cortex volumetry (RCV) for calculation of SRF have shown similar results in highly selected patient collectives with normal renal function (i.e. living kidney donors). This study aims to compare MAG3-scintigraphy and CT-RCV within a large unselected patient collective including patients with impaired renal function. For this assessment, 279 datasets (131 men, 148 women; mean age: 54.2 ± 12.9 years, range: 24-84 years) of patients who underwent MAG3-scintigraphy and contrast-enhanced abdominal CT within two weeks were retrospectively analyzed. Two independent readers assessed the CT-RCV in all CT datasets using a semi-automated volumetry tool. The MAG3-scintigraphy and CT-RCV methods were compared, stratified for the eGFR. Statistical analysis included descriptive statistics as well as inter- observer agreement. The absolute mean difference between the percentage contribution of the left and the right kidneys in total MAG3-clearance was 8.6%. Independent of eGFR, an overall sufficient agreement between both methods was established in all patients. A relatively small, tolerable systemic error resulted in an underestimation (max. 2%) of the left renal contribution to overall RCV. The results demonstrate that CT-RCV is a potential clinical replacement for MAG3-scintigraphy for calculation of SRF: CT-RCV demonstrates clinically tolerable differences with MAG3-scintigraphy, independent of patient eGFR. The relative complexity of the RCV method utilized is a potential limitation and may have contributed to the acceptable but only fair to moderate level of intra-reader reliability. Copyright © 2018 Elsevier B.V. All rights reserved.

  16. Characterization of developmental and stress mediated expression of cinnamoyl-CoA reductase (CCR) in kenaf (Hibiscus cannabinus L.)

    Science.gov (United States)

    Cinnamoyl-CoA reductase (CCR) is an important enzyme for lignin biosynthesis as it catalyzes the first specific committed step in monolignol biosynthesis. We have cloned a full length coding sequence of CCR from kenaf (Hibiscus cannabinus L.), which contains a 1,020-bp open reading frame (ORF), enco...

  17. CCR6-dependent positioning of memory B cells is essential for their ability to mount a recall response to antigen.

    Science.gov (United States)

    Elgueta, Raul; Marks, Ellen; Nowak, Elizabeth; Menezes, Shinelle; Benson, Micah; Raman, Vanitha S; Ortiz, Carla; O'Connell, Samuel; Hess, Henry; Lord, Graham M; Noelle, Randolph

    2015-01-15

    Chemokine-dependent localization of specific B cell subsets within the immune microarchitecture is essential to ensure successful cognate interactions. Although cognate interactions between T cells and memory B cells (B(mem)) are essential for the secondary humoral immune responses, the chemokine response patterns of B(mem) cells are largely unknown. In contrast to naive B cells, this study shows that Ag-specific B(mem) cells have heightened expression of CCR6 and a selective chemotactic response to the CCR6 ligand, CCL20. Although CCR6 appears be nonessential for the initial clonal expansion and maintenance of B(mem), CCR6 is essential for the ability of B(mem) to respond to a recall response to their cognate Ag. This dependency was deemed intrinsic by studies in CCR6-deficient mice and in bone marrow chimeric mice where CCR6 deficiency was limited to the B cell lineage. Finally, the mis-positioning of CCR6-deficient B(mem) was revealed by immunohistological analysis with an altered distribution of CCR6-deficient B(mem) from the marginal and perifollicular to the follicular/germinal center area. Copyright © 2015 by The American Association of Immunologists, Inc.

  18. CCR6-dependent positioning of memory B cells is essential for their ability to mount a recall response to antigen

    Science.gov (United States)

    Elgueta, Raul; Marks, Ellen; Nowak, Elizabeth; Menezes, Shinelle; Benson, Micah; Raman, Vanitha S.; Ortiz, Carla; O’Connell, Samuel; Hess, Henry; Lord, Graham M.; Noelle, Randolph

    2014-01-01

    Chemokine-dependent localization of specific B cell subsets within the immune microarchitecture is essential to insure successful cognate interactions. While cognate interactions between T cells and memory B cells (Bmem)5 are essential for the secondary humoral immune responses, the chemokine response patterns of Bmem cells are largely unknown. In contrast to naïve B cells, this study shows that antigen-specific Bmem cells have heightened expression of CCR6 and a selective chemotactic response to the CCR6 ligand, CCL20. While CCR6 appears be non-essential for the initial clonal expansion and maintenance of Bmem, CCR6 is essential for the ability of Bmem to respond to a recall response to their cognate antigen. This dependency was deemed intrinsic by studies in CCR6-deficient mice and in bone-marrow chimeric mice where CCR6 deficiency was limited to the B cell lineage. Finally, the mis-positioning of CCR6-deficient Bmem was revealed by immunohistological analysis with an altered distribution of CCR6-deficient Bmem from the marginal and perifollicular to the follicular/germinal center area. PMID:25505290

  19. Exploring a model of human chemokine receptor CCR2 in presence of TAK779: A membrane based molecular dynamics study

    Science.gov (United States)

    Balupuri, Anand; Sobhia, M. Elizabeth

    2014-04-01

    Chemokine receptor 2 (CCR2) is a G-protein coupled receptor (GPCR) and a crucial target for various inflammation-driven diseases. In the present study, molecular docking and molecular dynamics simulations were performed on a CCR2 homology model. This work includes the comparative MD simulations of uncomplexed and ‘antagonist-complexed’ CCR2 models. These simulations yield insights into the binding mechanism of antagonist TAK779 and improve the understanding of various structural changes induced by the ligand in the CCR2 protein. Here, one 20 ns MD simulation was carried out on the uncomplexed CCR2 model in lipid bilayer to explore the effects of lipid membrane on the protein. Another 20 ns MD simulation was performed under the similar conditions on the docked CCR2-TAK779 complex. An alteration in the position and orientation of the ligand in binding site was observed after the simulation. Examination of protein-ligand complex suggested that TAK779 produced a greater structural change on the TM-III, TM-IV, TM-V and TM-VI than TM-I, TM-II and TM-VII. Interaction networks involving the conserved residues of uncomplexed and ‘antagonist-complexed’ CCR2 models were also examined. The major difference was observed to be the role of conserved residues of the DRY motif of TM-III and the NPxxY motif of TM-VII of CCR2.

  20. Evidence favoring the involvement of CC chemokine receptor (CCR) 5 in T-lymphocyte accumulation in optic neuritis

    DEFF Research Database (Denmark)

    Sørensen, Torben Lykke; Ransohoff, R M; Jensen, J

    2003-01-01

    To define the relationships between levels of chemokine receptor (CCR)5+ T-cells in blood and cerebrospinal fluid (CSF) of optic neuritis (ON) and control patients (CON).......To define the relationships between levels of chemokine receptor (CCR)5+ T-cells in blood and cerebrospinal fluid (CSF) of optic neuritis (ON) and control patients (CON)....

  1. Preclinical and clinical investigation of a CCR5 antagonist, AZD5672, in patients with rheumatoid arthritis receiving methotrexate

    NARCIS (Netherlands)

    Gerlag, Daniëlle M.; Hollis, Sally; Layton, Mark; Vencovský, Jiří; Szekanecz, Zoltán; Braddock, Martin; Tak, Paul P.; Oparanov, Boycho; Stoilov, Rumen; Yaneva, Tanya; Batalov, Anastas; Arteaga, Edgardo Tobias; Escalante, William Otero; Velez, Patricia; Restrepo, Jose Molina; Augustinova, Sevda; Blahova, Anna; Dvorak, Zdenek; Novosad, Libor; Rosa, Jan; Stehlikova, Helena; Vitek, Petr; Balazs, Tibor; Seregely, Katalin; Szombati, Istvan; Tarjan, Katalin; Csengei, Gabor; Galeazzi, Mauro; Saleniece, Sarmite; Saulite-Kandevica, Daina; Coleiro, Bernard; Badurski, Janusz; Brzosko, Marek; Chudzik, Dariusz; Gruszecka-Marczynska, Katarzyna; Hensel, Joanna; Pokrzywnicka-Gajek, Ines; Korpanty-Danda, Joanna; Sochocka-Bykowska, Malgorzata; Tlustochowicz, Witold; Stopinska-Polaszewska, Maria; Gluszko, Piotr; Nedelcovici, Corina; Radulescu, Florin; Gavrila, Mirea; Tanasescu, Coman; Korshunov, Nikolay; Matsievskaia, Galina; Damjanov, Nemanja; Dimic, Aleksandar

    2010-01-01

    To investigate both the preclinical effects of blocking the chemokine receptor CCR5 and the clinical effects of this approach on the signs and symptoms of rheumatoid arthritis (RA) in patients with active disease. Preclinical evaluations of AZD5672, a small-molecule antagonist of CCR5, were

  2. Blood expression levels of chemokine receptor CCR3 and chemokine CCL11 in age-related macular degeneration

    DEFF Research Database (Denmark)

    Falk, Mads Krüger; Singh, Amardeep; Faber, Carsten

    2014-01-01

    Dysregulation of the CCR3/CCL11 pathway has been implicated in the pathogenesis of choroidal neovascularisation, a common feature of late age-related macular degeneration (AMD). The aim of this study was to investigate the expression of CCR3 and its ligand CCL11 in peripheral blood in patients...

  3. A highly selective CCR2 chemokine agonist encoded by human herpesvirus 6

    DEFF Research Database (Denmark)

    Lüttichau, Hans R; Clark-Lewis, Ian; Jensen, Peter Østrup

    2003-01-01

    The chemokine-like, secreted protein product of the U83 gene from human herpesvirus 6, here named vCCL4, was chemically synthesized to be characterized in a complete library of the 18 known human chemokine receptors expressed individually in stably transfected cell lines. vCCL4 was found to cause...... being equally or more efficacious in causing cell migration than CCL2 and CCL7 and considerably more efficacious than CCL8 and CCL13. It is concluded that human herpesvirus 6 encodes a highly selective and efficacious CCR2 agonist, which will attract CCR2 expressing cells, for example macrophages...

  4. Differential evolution of a CXCR4-using HIV-1 strain in CCR5wt/wt and CCR5∆32/∆32 hosts revealed by longitudinal deep sequencing and phylogenetic reconstruction.

    Science.gov (United States)

    Le, Anh Q; Taylor, Jeremy; Dong, Winnie; McCloskey, Rosemary; Woods, Conan; Danroth, Ryan; Hayashi, Kanna; Milloy, M-J; Poon, Art F Y; Brumme, Zabrina L

    2015-12-03

    Rare individuals homozygous for a naturally-occurring 32 base pair deletion in the CCR5 gene (CCR5∆32/∆32) are resistant to infection by CCR5-using ("R5") HIV-1 strains but remain susceptible to less common CXCR4-using ("X4") strains. The evolutionary dynamics of X4 infections however, remain incompletely understood. We identified two individuals, one CCR5wt/wt and one CCR5∆32/∆32, within the Vancouver Injection Drug Users Study who were infected with a genetically similar X4 HIV-1 strain. While early-stage plasma viral loads were comparable in the two individuals (~4.5-5 log10 HIV-1 RNA copies/ml), CD4 counts in the CCR5wt/wt individual reached a nadir of 250 cells/mm(3) in the CCR5∆32/∆32 individual. Ancestral phylogenetic reconstructions using longitudinal envelope-V3 deep sequences suggested that both individuals were infected by a single transmitted/founder (T/F) X4 virus that differed at only one V3 site (codon 24). While substantial within-host HIV-1 V3 diversification was observed in plasma and PBMC in both individuals, the CCR5wt/wt individual's HIV-1 population gradually reverted from 100% X4 to ~60% R5 over ~4 years whereas the CCR5∆32/∆32 individual's remained consistently X4. Our observations illuminate early dynamics of X4 HIV-1 infections and underscore the influence of CCR5 genotype on HIV-1 V3 evolution.

  5. 99mTc-MAG3: can it be a viable alternative to 99mTc-DTPA ?

    International Nuclear Information System (INIS)

    Bal, C.S.; Padhy, A.K.; Nair, R.; Gopinath, P.G.

    1991-01-01

    The purpose of this study was to assess the potentials of 99m Tc MAG 3 to replace universally used 99m Tc-DTPA as a routine renal agent. Five patients with different nephrological problems were first studied with 99m Tc MAG 3 and then reinvestigated with 99m Tc-DTPA two to seven days later. Renal MAG 3 gamma camera images were found to be almost identical with those of 99m Tc-DTPA images except high hepatic and splenic uptake of the former compound in four out of five patients (80%) irrespective of kidney function. MAG 3 and DTPA renograms showed identical differential renal uptake function (r=0.87) with slightly higher uptake in right kidneys. Time to reach the peak correlated well (r=0.91). Time to reach half maximum renal activity was also found to be almost identical (r=0.97) for MAG 3 and DTPA. It was felt that the age old 99m Tc-DTPA is as good a compound as 99m Tc MAG 3 with regard to imaging and assessment of renal uptake, drainage and differential renal functions. 99m Tc-DTPA is much cheaper, readily available in India and stable to suit the logistics in a busy nuclear medicine department for routine renography. (author). 10 refs., 2 figs., 3 tabs

  6. Synthesis, formulation of nucleo-equipment and biological studies of the 99m Tc-MAG3

    International Nuclear Information System (INIS)

    Reyes H, L.; Lezama C, J.; Ferro F, G.

    1991-10-01

    Technetium-99m-mercaptoacetyl glycylglycylglycine ( 99m Tc-MAG 3 ) is introduced to replace o-iodohippurate (OIH) for renal function studies. In this paper we present the synthesis, labelling and biological evaluation of 99m Tc- MAG 3 prepared in our laboratory. The precursor s-benzoyl-mercaptoacetyl glycyl glycylglycine (Bz-MAG 3 ) was synthesized by condensation of glycylglycylglycine with chloroacetyl chloride to obtain chloroacetyl glycylglycylglycine and this product was condensate with sodium thiobenzoate. The Bz-MAG 3 was characterized by IR and NMR. The labelling with 99m Tc was carried out at pH 9.0 using stannous chloride as a reducing agent with heating to boiling for 15 min. The benzoyl group is lost in this step, forming 99m Tc-MAG 3 complex with radiochemical purity of 99%. The biodistribution properties were evaluated in mice and a rapid renal extraction was apparent at the 10 minutes value (51.65% of the injected dose). The radiotracer was administered to 5 patients showing a good biological behavior. Based on these results, the 99m Tc-MAG 3 is expected to have widespread clinical utility in Mexico. (Author)

  7. Mag-seeding of rat bone marrow stromal cells into porous hydroxyapatite scaffolds for bone tissue engineering.

    Science.gov (United States)

    Shimizu, Kazunori; Ito, Akira; Honda, Hiroyuki

    2007-09-01

    Bone tissue engineering has been investigated as an alternative strategy for autograft transplantation. In the process of tissue engineering, cell seeding into three-dimensional (3-D) scaffolds is the first step for constructing 3-D tissues. We have proposed a methodology of cell seeding into 3-D porous scaffolds using magnetic force and magnetite nanoparticles, which we term Mag-seeding. In this study, we applied this Mag-seeding technique to bone tissue engineering using bone marrow stromal cells (BMSCs) and 3-D hydroxyapatite (HA) scaffolds. BMSCs were magnetically labeled with our original magnetite cationic liposomes (MCLs) having a positive surface charge to improve adsorption to cell surface. Magnetically labeled BMSCs were seeded onto a scaffold, and a 1-T magnet was placed under the scaffold. By using Mag-seeding, the cells were successfully seeded into the internal space of scaffolds with a high cell density. The cell seeding efficiency into HA scaffolds by Mag-seeding was approximately threefold larger than that by static-seeding (conventional method, without a magnet). After a 14-d cultivation period using the osteogenic induction medium by Mag-seeding, the level of two representative osteogenic markers (alkaline phosphatase and osteocalcin) were significantly higher than those by static-seeding. These results indicated that Mag-seeding of BMSCs into HA scaffolds is an effective approach to bone tissue engineering.

  8. Medicinal chemistry of small molecule CCR5 antagonists for blocking HIV-1 entry: a review of structural evolution.

    Science.gov (United States)

    Tian, Ye; Zhang, Dujuan; Zhan, Peng; Liu, Xinyong

    2014-01-01

    CCR5, a member of G protein-coupled receptors superfamily, plays an important role in the HIV-1 entry process. Antagonism of this receptor finally leads to the inhibition of R5 strains of HIV entry into the human cells. The identification of CCR5 antagonists as antiviral agents will provide more option for HAART. Now, more than a decade after the first small molecule CCR5 inhibitor was discovered, great achievements have been made. In this article, we will give a brief introduction of several series of small molecule CCR5 antagonists, focused on their appealing structure evolution, essential SAR information and thereof the enlightenment of strategies on CCR5 inhibitors design.

  9. CCR5 Gene Disruption via Lentiviral Vectors Expressing Cas9 and Single Guided RNA Renders Cells Resistant to HIV-1 Infection

    Science.gov (United States)

    Liu, Jingjing; Zhang, Di; Kimata, Jason T.; Zhou, Paul

    2014-01-01

    CCR5, a coreceptor for HIV-1 entry, is a major target for drug and genetic intervention against HIV-1. Genetic intervention strategies have knocked down CCR5 expression levels by shRNA or disrupted the CCR5 gene using zinc finger nucleases (ZFN) or Transcription activator-like effector nuclease (TALEN). In the present study, we silenced CCR5 via CRISPR associated protein 9 (Cas9) and single guided RNAs (sgRNAs). We constructed lentiviral vectors expressing Cas9 and CCR5 sgRNAs. We show that a single round transduction of lentiviral vectors expressing Cas9 and CCR5 sgRNAs into HIV-1 susceptible human CD4+ cells yields high frequencies of CCR5 gene disruption. CCR5 gene-disrupted cells are not only resistant to R5-tropic HIV-1, including transmitted/founder (T/F) HIV-1 isolates, but also have selective advantage over CCR5 gene-undisrupted cells during R5-tropic HIV-1 infection. Importantly, using T7 endonuclease I assay we did not detect genome mutations at potential off-target sites that are highly homologous to these CCR5 sgRNAs in stably transduced cells even at 84 days post transduction. Thus we conclude that silencing of CCR5 via Cas9 and CCR5-specific sgRNAs could be a viable alternative strategy for engineering resistance against HIV-1. PMID:25541967

  10. Structure-Activity Relationships and Identification of Optmized CC-Chemokine Receptor CCR1, 5, and 8 Metal-Ion Chelators

    DEFF Research Database (Denmark)

    Chalikiopoulos, Alexander; Thiele, Stefanie; Malmgaard-Clausen, Mikkel

    2013-01-01

    Chemokine receptors are involved in trafficking of leukocytes and represent targets for autoimmune conditions, inflammatory diseases, viral infections, and cancer. We recently published CCR1, CCR8, and CCR5 agonists and positive modulators based on a three metal-ion chelator series: 2,2'-bipyridi...

  11. Elucidating a Key Anti-HIV-1 and Cancer-Associated Axis: The Structure of CCL5 (Rantes) in Complex with CCR5

    Science.gov (United States)

    Tamamis, Phanourios; Floudas, Christodoulos A.

    2014-06-01

    CCL5 (RANTES) is an inflammatory chemokine which binds to chemokine receptor CCR5 and induces signaling. The CCL5:CCR5 associated chemotactic signaling is of critical biological importance and is a potential HIV-1 therapeutic axis. Several studies provided growing evidence for the expression of CCL5 and CCR5 in non-hematological malignancies. Therefore, the delineation of the CCL5:CCR5 complex structure can pave the way for novel CCR5-targeted drugs. We employed a computational protocol which is primarily based on free energy calculations and molecular dynamics simulations, and report, what is to our knowledge, the first computationally derived CCL5:CCR5 complex structure which is in excellent agreement with experimental findings and clarifies the functional role of CCL5 and CCR5 residues which are associated with binding and signaling. A wealth of polar and non-polar interactions contributes to the tight CCL5:CCR5 binding. The structure of an HIV-1 gp120 V3 loop in complex with CCR5 has recently been derived through a similar computational protocol. A comparison between the CCL5 : CCR5 and the HIV-1 gp120 V3 loop : CCR5 complex structures depicts that both the chemokine and the virus primarily interact with the same CCR5 residues. The present work provides insights into the blocking mechanism of HIV-1 by CCL5.

  12. Neutralizing antibody and anti-retroviral drug sensitivities of HIV-1 isolates resistant to small molecule CCR5 inhibitors

    International Nuclear Information System (INIS)

    Pugach, Pavel; Ketas, Thomas J.; Michael, Elizabeth; Moore, John P.

    2008-01-01

    The small molecule CCR5 inhibitors are a new class of drugs for treating infection by human immunodeficiency virus type 1 (HIV-1). They act by binding to the CCR5 co-receptor and preventing its use during HIV-1-cell fusion. Escape mutants can be raised against CCR5 inhibitors in vitro and will arise when these drugs are used clinically. Here, we have assessed the responses of CCR5 inhibitor-resistant viruses to other anti-retroviral drugs that act by different mechanisms, and their sensitivities to neutralizing antibodies (NAbs). The rationale for the latter study is that the resistance pathway for CCR5 inhibitors involves changes in the HIV-1 envelope glycoproteins (Env), which are also targets for NAbs. The escape mutants CC101.19 and D1/85.16 were selected for resistance to AD101 and vicriviroc (VVC), respectively, from the primary R5 HIV-1 isolate CC1/85. Each escape mutant was cross-resistant to other small molecule CCR5 inhibitors (aplaviroc, maraviroc, VVC, AD101 and CMPD 167), but sensitive to protein ligands of CCR5: the modified chemokine PSC-RANTES and the humanized MAb PRO-140. The resistant viruses also retained wild-type sensitivity to the nucleoside reverse transcriptase inhibitor (RTI) zidovudine, the non-nucleoside RTI nevirapine, the protease inhibitor atazanavir and other attachment and fusion inhibitors that act independently of CCR5 (BMS-806, PRO-542 and enfuvirtide). Of note is that the escape mutants were more sensitive than the parental CC1/85 isolate to a subset of neutralizing monoclonal antibodies and to some sera from HIV-1-infected people, implying that sequence changes in Env that confer resistance to CCR5 inhibitors can increase the accessibility of some NAb epitopes. The need to preserve NAb resistance may therefore be a constraint upon how escape from CCR5 inhibitors occurs in vivo

  13. 3D Stagnation instabilities in MagLIF loads on the Z Generator

    Science.gov (United States)

    Jennings, Christopher

    2017-10-01

    Experiments with Magnetized Liner Inertial Fusion (MagLIF) loads have successfully demonstrated the premise of magnetized fusion. While these experiments are increasingly well diagnosed, many of the measurements (particularly during stagnation) are time integrated, limited in spatial resolution or require additional assumptions to interpret in the context of a structured, rapidly evolving system. As such, there is some ambiguity over what may be limiting performance. Poor laser coupling in preheating the fuel prior to implosion has been suggested as a mechanism. Mix of high Z contaminants that cool the fuel is also a significant concern. In addition, time integrated crystal imaging has shown significant structure in the final fuel assembly indicating potential disruption from instabilities. Understanding the balance between these degradation mechanisms is vital to progress with MagLif. We compare several sets of experimental data with synthetically generated data from systematically varied 3D resistive-MHD simulations to gain insight into the relative contributions of different degradation mechanisms. We demonstrate how some measurements strongly indicate disruption from liner material penetrating into the fuel at stagnation, and discuss the implications this has for how MagLif targets work and scale to larger drive currents. We then explore the extent to which different combinations of instability development, current delivery, high-Z mix into the fuel and initial laser deposition can be differentiated in our existing measurements. Better determining the dominant degradation mechanisms can directly influence the direction we take to improve performance, or our confidence in scaling these targets to higher currents. Sandia National Laboratories is a multimission laboratory managed and operated by National Technology and Engineering Solutions of Sandia LLC, a wholly owned subsidiary of Honeywell International Inc. for the U.S. DoE's NNSA under contract DE-NA0003525.

  14. MagRad: A code to optimize the operation of superconducting magnets in a radiation environment

    International Nuclear Information System (INIS)

    Yeaw, C.T.

    1995-01-01

    A powerful computational tool, called MagRad, has been developed which optimizes magnet design for operation in radiation fields. Specifically, MagRad has been used for the analysis and design modification of the cable-in-conduit conductors of the TF magnet systems in fusion reactor designs. Since the TF magnets must operate in a radiation environment which damages the material components of the conductor and degrades their performance, the optimization of conductor design must account not only for start-up magnet performance, but also shut-down performance. The degradation in performance consists primarily of three effects: reduced stability margin of the conductor; a transition out of the well-cooled operating regime; and an increased maximum quench temperature attained in the conductor. Full analysis of the magnet performance over the lifetime of the reactor includes: radiation damage to the conductor, stability, protection, steady state heat removal, shielding effectiveness, optimal annealing schedules, and finally costing of the magnet and reactor. Free variables include primary and secondary conductor geometric and compositional parameters, as well as fusion reactor parameters. A means of dealing with the radiation damage to the conductor, namely high temperature superconductor anneals, is proposed, examined, and demonstrated to be both technically feasible and cost effective. Additionally, two relevant reactor designs (ITER CDA and ARIES-II/IV) have been analyzed. Upon addition of pure copper strands to the cable, the ITER CDA TF magnet design was found to be marginally acceptable, although much room for both performance improvement and cost reduction exists. A cost reduction of 10-15% of the capital cost of the reactor can be achieved by adopting a suitable superconductor annealing schedule. In both of these reactor analyses, the performance predictive capability of MagRad and its associated costing techniques have been demonstrated

  15. Creating a FIESTA (Framework for Integrated Earth Science and Technology Applications) with MagIC

    Science.gov (United States)

    Minnett, R.; Koppers, A. A. P.; Jarboe, N.; Tauxe, L.; Constable, C.

    2017-12-01

    The Magnetics Information Consortium (https://earthref.org/MagIC) has recently developed a containerized web application to considerably reduce the friction in contributing, exploring and combining valuable and complex datasets for the paleo-, geo- and rock magnetic scientific community. The data produced in this scientific domain are inherently hierarchical and the communities evolving approaches to this scientific workflow, from sampling to taking measurements to multiple levels of interpretations, require a large and flexible data model to adequately annotate the results and ensure reproducibility. Historically, contributing such detail in a consistent format has been prohibitively time consuming and often resulted in only publishing the highly derived interpretations. The new open-source (https://github.com/earthref/MagIC) application provides a flexible upload tool integrated with the data model to easily create a validated contribution and a powerful search interface for discovering datasets and combining them to enable transformative science. MagIC is hosted at EarthRef.org along with several interdisciplinary geoscience databases. A FIESTA (Framework for Integrated Earth Science and Technology Applications) is being created by generalizing MagIC's web application for reuse in other domains. The application relies on a single configuration document that describes the routing, data model, component settings and external services integrations. The container hosts an isomorphic Meteor JavaScript application, MongoDB database and ElasticSearch search engine. Multiple containers can be configured as microservices to serve portions of the application or rely on externally hosted MongoDB, ElasticSearch, or third-party services to efficiently scale computational demands. FIESTA is particularly well suited for many Earth Science disciplines with its flexible data model, mapping, account management, upload tool to private workspaces, reference metadata, image

  16. Kinetics of manganese in MAG/MIG welding with a 18/8/6 wire

    OpenAIRE

    Tušek, Janez

    2001-01-01

    The paper deals with a study of MAG/MIG welding of low-alloy ferritic steel and highalloy austenitic steel with a 18/8/6 wire. Manganese burn-off from the wire in welding a single-V butt weld was studied. It was found that manganese burns off in the arc during melting of a droplet at the wire end, and from the weld pool during weld formation. The range of manganese burn-off depends mainly on the type of shielding gas used and the arc length, i.e., from the arc voltage. The manganese burn-off ...

  17. Evaluation of 99mTc-MAG3 (mercaptoacetyltriglycine) renography for pediatric patients

    International Nuclear Information System (INIS)

    Tabuchi, Kojiro; Adachi, Itaru; Doi, Kenji; Hou, Nobuyoshi; Komori, Tsuyoshi; Nakata, Yasunobu; Matsui, Ritsuo; Sueyoshi, Kouzou; Narabayashi, Isamu

    1999-01-01

    It is difficult to evaluate renal function with 99m Tc-MAG 3 renography in both adult and pediatric patients. We examined 109 pediatric patients with various renal diseases using 99m Tc-MAG 3 renography. Tenal diseases were classified as follows: 9 vesicoureteral reflux, 4 ureteropelvic junctional stenosis, 3 double pelvis, 23 hydronephrosis, 4 glomerulonephritis, 4 nephrotic syndrome, 24 hemolytic uremic syndrome, 10 others; and 24 patients without abnormal findings on other examinations. After hydration and sedation, 100-200 MBq of 99m Te-MAG 3 was injected intravenously. All patients were placed in the supine position, and dynamic data acquisition at 12 sec/frame x 100 frames was performed from the back. The renograms were prepared with the ROIs (regions of interest) set to include the entire kidney. Tmax and T1/2 of renograms were measured for 26 kidneys with no abnormal findings. The correlations between Tmax or T1/2 and age (days after birth) were determined by a linear or logarithmic function. The logarithmic function (Y=7.49-0.56 log e X, r 2 =0.134) yielded a higher correlation than did the linear function (Y=5.16-0.00194X, r 2 =0.089) between Tmax and age. For T1/2 and age (days after birth), the linear function (Y=8.07-0.00451X, r 2 =0.222) yielded a higher correlation than the logarithmic function (Y=11.9-0.986 log e X, r 2 =0.192). Our findings suggest that prolonged Tmax is normalized more rapidly than T1/2 after birth in infants. A delayed excretion phase is not suggestive of renal dysfunction, but is characteristic of renograms in pediatric patients. Abnormality was detected in all patients with hydronephrosis using 99m Tc-MAG 3 renography. On the other hand, a quantitative study was required because renography detected no abnormality for some of patients with disorders of renal parenchyma. (author)

  18. Validation of alternative methods of preparing 99mTc-MAG3

    International Nuclear Information System (INIS)

    Seetharaman, Shankar; Sosabowski, Michael H.; Ballinger, James R.

    2007-01-01

    Parameters in the preparation of 99m Tc-mertiatide ( 99m Tc-MAG3) were investigated to determine the importance of total activity, activity concentration, boiling time, and delay before boiling for the radiochemical purity (RCP) and stability of the product. Satisfactory RCP results (>90%) were obtained over a range of concentrations including a dilute preparation for paediatric use. RCP was not affected by the time between the addition of pertechnetate and boiling, but low RCP (<60%) resulted when the kit was boiled for less than 10 min

  19. Validation of alternative methods of preparing {sup 99m}Tc-MAG3

    Energy Technology Data Exchange (ETDEWEB)

    Seetharaman, Shankar [Department of Pharmacy, Guy' s and St Thomas' Hospital, Lambeth Palace Road, London SE1 9EH (United Kingdom); Sosabowski, Michael H. [School of Pharmacy and Biomolecular Sciences, University of Brighton, Moulsecoomb (United Kingdom); Ballinger, James R. [Department of Nuclear Medicine, Guy' s and St Thomas' Hospital, St Thomas Street, London SE1 9RT (United Kingdom)], E-mail: james.ballinger@gstt.nhs.uk

    2007-11-15

    Parameters in the preparation of {sup 99m}Tc-mertiatide ({sup 99m}Tc-MAG3) were investigated to determine the importance of total activity, activity concentration, boiling time, and delay before boiling for the radiochemical purity (RCP) and stability of the product. Satisfactory RCP results (>90%) were obtained over a range of concentrations including a dilute preparation for paediatric use. RCP was not affected by the time between the addition of pertechnetate and boiling, but low RCP (<60%) resulted when the kit was boiled for less than 10 min.

  20. Renal scintigraphy in the 21st Century {sup 99m} Tc-MAG{sub 3} with zero time injection of furosemide (MAG{sub 3}-F{sub 0}): a fast and easy protocol, one for all indications. Part 3. Clinical experience. Congenital disorders

    Energy Technology Data Exchange (ETDEWEB)

    Sfakianakis, G.N. [Professor of Radiology and Pediatrics, Director Division of Nuclear Medicine, University of Miami, School of Medicine, Florida (United States)

    2007-07-01

    In this work the Protocol for MAG{sub 3}-F{sub 0} is presented. Patient preparation, easy (only restriction, oral hydration, no bladder cathartic). Dynamic study (iv 1-10 mCi MAG{sub 3} + 40-80 mg LASIX), simultaneous injection of furosemide: MAG{sub 3}-F{sub 0}, duration of the study: 25 minutes. Tomography-SPECT (20 mCi MAG{sub 3}). No diuretic needed, duration of the study: 4 minutes. (Author)

  1. Orphan chemokine receptors in neuroimmunology : functional and pharmacological analysis of L-CCR and HCR

    NARCIS (Netherlands)

    Zuurman, Michael Wilhelmer

    2003-01-01

    In this thesis we have investigated the expression and biological activity of the orphan chemokine receptors L-CCR/HCR in astrocytes and microglia. Several lines of evidence indicate that the chemokines CCL2, CCL5, CCL7 and CCL8 are agonists for these receptors. Although a variety of biological

  2. Why CCR: A conversation with Physician Assistant Julia Friend | Center for Cancer Research

    Science.gov (United States)

    "Where else can you make such a profound difference not only for the individual now, but for those who come in the future? It is hard work, good work and worth doing well.” Physician Assistant Julia Friend answers our questions about why she loves working for CCR. Read more...

  3. Differential CCR7 Targeting in Dendritic Cells by Three Naturally Occurring CC-Chemokines

    DEFF Research Database (Denmark)

    Hjorto, Gertrud M.; Larsen, Olav; Steen, Anne

    2016-01-01

    The CCR7 ligands CCL19 and CCL21 are increasingly recognized as functionally different (biased). Using mature human dendritic cells (DCs), we show that CCL19 is more potent than CCL21 in inducing 3D chemotaxis. Intriguingly, CCL21 induces prolonged and more efficient ERK1/2 activation compared...

  4. Impact of CCR5 Delta32/+ deletion on herpes zoster among HIV-1-infected homosexual men

    NARCIS (Netherlands)

    Krol, Anneke; Lensen, Ruud; Veenstra, Jan; Prins, Maria; Schuitemaker, Hanneke; Coutinho, Roel A.

    2006-01-01

    The association between the presence of CCR5 Delta32 heterozygosity and incidence of clinical herpes zoster was studied among 296 homosexual men from the Amsterdam cohort study (ACS) infected with human immunodeficiency virus type I (HIV-1) with an estimated date of seroconversion. Of them 63 were

  5. Distinct modes of recruitment of the CCR4-NOT complex by Drosophila and vertebrate Nanos.

    Science.gov (United States)

    Raisch, Tobias; Bhandari, Dipankar; Sabath, Kevin; Helms, Sigrun; Valkov, Eugene; Weichenrieder, Oliver; Izaurralde, Elisa

    2016-05-02

    Nanos proteins repress the expression of target mRNAs by recruiting effector complexes through non-conserved N-terminal regions. In vertebrates, Nanos proteins interact with the NOT1 subunit of the CCR4-NOT effector complex through a NOT1 interacting motif (NIM), which is absent in Nanos orthologs from several invertebrate species. Therefore, it has remained unclear whether the Nanos repressive mechanism is conserved and whether it also involves direct interactions with the CCR4-NOT deadenylase complex in invertebrates. Here, we identify an effector domain (NED) that is necessary for the Drosophila melanogaster (Dm) Nanos to repress mRNA targets. The NED recruits the CCR4-NOT complex through multiple and redundant binding sites, including a central region that interacts with the NOT module, which comprises the C-terminal domains of NOT1-3. The crystal structure of the NED central region bound to the NOT module reveals an unanticipated bipartite binding interface that contacts NOT1 and NOT3 and is distinct from the NIM of vertebrate Nanos. Thus, despite the absence of sequence conservation, the N-terminal regions of Nanos proteins recruit CCR4-NOT to assemble analogous repressive complexes. © 2016 The Authors. Published under the terms of the CC BY NC ND 4.0 license.

  6. TRPV1 and the MCP-1/CCR2 Axis Modulate Post-UTI Chronic Pain.

    Science.gov (United States)

    Rosen, John M; Yaggie, Ryan E; Woida, Patrick J; Miller, Richard J; Schaeffer, Anthony J; Klumpp, David J

    2018-05-08

    The etiology of chronic pelvic pain syndromes remains unknown. In a murine urinary tract infection (UTI) model, lipopolysaccharide of uropathogenic E. coli and its receptor TLR4 are required for post-UTI chronic pain development. However, downstream mechanisms of post-UTI chronic pelvic pain remain unclear. Because the TRPV1 and MCP-1/CCR2 pathways are implicated in chronic neuropathic pain, we explored their role in post-UTI chronic pain. Mice were infected with the E. coli strain SΦ874, known to produce chronic allodynia, and treated with the TRPV1 antagonist capsazepine. Mice treated with capsazepine at the time of SΦ874 infection failed to develop chronic allodynia, whereas capsazepine treatment of mice at two weeks following SΦ874 infection did not reduce chronic allodynia. TRPV1-deficient mice did not develop chronic allodynia either. Similar results were found using novelty-suppressed feeding (NSF) to assess depressive behavior associated with neuropathic pain. Imaging of reporter mice also revealed induction of MCP-1 and CCR2 expression in sacral dorsal root ganglia following SΦ874 infection. Treatment with a CCR2 receptor antagonist at two weeks post-infection reduced chronic allodynia. Taken together, these results suggest that TRPV1 has a role in the establishment of post-UTI chronic pain, and CCR2 has a role in maintenance of post-UTI chronic pain.

  7. Performance Evaluation of Manual and Automated (MagNA Pure Nucleic Acid Isolation in HPV Detection and Genotyping Using Roche Linear Array HPV Test

    Directory of Open Access Journals (Sweden)

    Aikaterini Chranioti

    2011-01-01

    Full Text Available Nucleic acids of human papillomavirus (HPV isolated by manual extraction method (AmpliLute and automated MagNA pure system were compared and evaluated with cytohistological findings in 253 women. The concordance level between AmpliLute and MagNA was very good 93.3% (=0.864, <.0001. Overall HPVpositivity detected by AmpliLute was 57.3% (30.4% as single and 27% as multiple infections in contrast to MagNA 54.5% (32% and 23%, resp.. Discrepant results observed in 25 cases: 11 MagNA(−/AmpliLute(+, 10 of which had positive histology; 5 MagNA(+/AmpliLute(− with negative histology; 8 MagNA(+/AmpliLute(+: in 7 of which AmpliLute detected extra HPV genotypes and 1 MagNA(invalid/AmpliLute(+ with positive histology. Both methods performed well when compared against cytological (area under curve (AUC of AmpliLute 0.712 versus 0.672 of MagNA and histological diagnoses (AUC of AmpliLute 0.935 versus 0.877 of MagNA, with AmpliLute showing a slightly predominance over MagNA. However, higher sensitivities, specificities, and positive/negative predictive values were obtained by AmpliLute.

  8. POSTNATAL PHENOTYPE AND LOCALIZATION OF SPINAL CORD V1 DERIVED INTERNEURONS

    Science.gov (United States)

    Alvarez, Francisco J.; Jonas, Philip C.; Sapir, Tamar; Hartley, Robert; Berrocal, Maria C.; Geiman, Eric J.; Todd, Andrew J.; Goulding, Martyn

    2010-01-01

    Developmental studies identified four classes (V0, V1, V2, V3) of embryonic interneurons in the ventral spinal cord. Very little however is known about their adult phenotypes. In order to further characterize interneuron cell types in the adult, the location, neurotransmitter phenotype, calcium-buffering protein expression and axon distributions of V1-derived neurons in the mouse spinal cord was determined. In the mature (P20 and older) spinal cord, most V1-derived neurons are located in lateral LVII and in LIX, few in medial LVII and none in LVIII. Approximately 40% express calbindin and/or parvalbumin, while few express calretinin. Of seven groups of ventral interneurons identified according to calcium-buffering protein expression, two groups (1 and 4) correspond with V1-derived neurons. Group 1 are Renshaw cells and intensely express calbindin and coexpress parvalbumin and calretinin. They represent 9% of the V1 population. Group 4 express only parvalbumin and represent 27% of V1-derived neurons. V1-derived group 4 neurons receive contacts from primary sensory afferents and are therefore proprioceptive interneurons and the most ventral neurons in this group receive convergent calbindin-IR Renshaw cell inputs. This subgroup resembles Ia inhibitory interneurons (IaINs) and represents 13% of V1-derived neurons. Adult V1-interneuron axons target LIX and LVII and some enter the deep dorsal horn. V1-axons do not cross the midline. V1 derived axonal varicosities were mostly (>80%) glycinergic and a third were GABAergic. None were glutamatergic or cholinergic. In summary, V1 interneurons develop into ipsilaterally projecting, inhibitory interneurons that include Renshaw cells, Ia inhibitory interneurons and other unidentified proprioceptive interneurons. PMID:16255029

  9. The SOGS-RA vs. the MAGS-7: prevalence estimates and classification congruence.

    Science.gov (United States)

    Langhinrichsen-Rohling, Jennifer; Rohling, Martin L; Rohde, Paul; Seeley, John R

    2004-01-01

    The purpose of this study was to compare the prevalence rate estimates and congruence in classification status derived from two popular measures of adolescent gambling (SOGS-RA and MAGS-7). Adolescents from three states (Alabama, Mississippi, and Oregon) completed an anonymous questionnaire ( n =1846 high school students total). Results indicate that the prevalence of probable adolescent pathological gambling varied both as a function of instrument and cut-off point utilized for classification (range 1.7%-8.2%). Classification groups (non-problem, at-risk, and problem gamblers) generated by both instruments were found to be associated with reports of gambling frequency, amount of money lost in one gambling occasion, and parental gambling problems. However, concern was raised because the MAGS-7 and the SOGS-RA had little congruence in their three-group classification decisions for specific individuals (e.g., only 20.5% agreement for problem gamblers). To improve clinical utility, an empirical case was made for using the SOGS-RA to generate a fourth group of adolescent gamblers, which we labeled "probable pathological gamblers" (SOGS-RA > or = 6). This group was differentiated from the remaining gambling groups on all the validity indices. The implications and limitations of these findings, as well as future directions, are discussed.

  10. Prognostic value of a CCR5 defective allele in pediatric HIV-1 infection.

    Science.gov (United States)

    Romiti, M L; Colognesi, C; Cancrini, C; Mas, A; Berrino, M; Salvatori, F; Orlandi, P; Jansson, M; Palomba, E; Plebani, A; Bertran, J M; Hernandez, M; de Martino, M; Amoroso, A; Tovo, P A; Rossi, P; Espanol, T; Scarlatti, G

    2000-01-01

    A deletion of 32 base pairs in the CCR5 gene (delta32 CCR5) has been linked to resistance to HIV-1 infection in exposed adults and to the delay of disease progression in infected adults. To determine the role of delta32 CCR5 in disease progression of HIV-1 infected children born to seropositive mothers, we studied a polymerase chain reaction in 301 HIV-1 infected, 262 HIV-1 exposed-uninfected and 47 HIV-1 unexposed-uninfected children of Spanish and Italian origin. Infected children were further divided into two groups according to their rate of HIV-1 disease progression: rapid progressors who developed severe clinical and/or immunological conditions within the second year of life, and delayed progressors with any other evolution of disease. Among the latter were the long-term, non-progressors (LTNP) who presented with mild or no symptoms of HIV-1 infection above 8 years of age. Viral phenotype was studied for 45 delayed progressors. No correlation was found between delta32 CCR5 and mother-to-child transmission of HIV-1. However, the frequency of the deletion was substantially higher in LTNP, compared with delayed (p = 0.019) and rapid progressors (p = 0.0003). In children carrying the delta32 CCRS mutation, the presence of MT-2 tropic virus isolate was associated with a severe immune suppression (p = 0.028); whereas, the presence of MT-2 negative viruses correlated with LTNP (p = 0.010). Given the rapidity and simplicity of the assay, the delta32 CCR5 mutation may be a useful predictive marker to identify children with delayed disease progression who, consequently, may not require immediate antiretroviral treatment.

  11. Comparison of experimental and theoretical integral cross sections for D+H2(v=1, j=1)→HD(v'=1, j')+H

    International Nuclear Information System (INIS)

    Kliner, D.A.V.; Adelman, D.E.; Zare, R.N.

    1991-01-01

    We have measured the nascent HD(v'=1, j') product rotational distribution from the reaction D+H 2 (v, j) in which the H 2 reagent was either thermal (v=0, j) or prepared in the level (v=1, j=1) by stimulated Raman pumping. Translationally hot D atoms were obtained by uv laser photolysis of DBr or DI. Photolysis of DBr generated D atoms with center-of-mass collision energies (E rel ) of 1.04 and 0.82 eV, which corresponded to the production of ground state Br and spin--orbit-excited Br*, respectively. The E rel values for DI photolysis were 1.38 and 0.92 eV. Quantum-state-specific detection of HD was accomplished via (2+1) resonance-enhanced multiphoton ionization and time-of-flight mass spectrometry. Vibrational excitation of the H 2 reagent results in substantial rotational excitation of the HD(v'=1) product and increases the reaction rate into v'=1 by about a factor of 4. Although the quantum-mechanical calculation of Blais et al. [Chem. Phys. Lett. 166, 11 (1990)] for the D+H 2 (v=1, j=1)→HD(v'=1, j')+H product rotational distribution at E rel =1.02 eV is in qualitative agreement with experiment, it does not quantitatively agree with the measured distribution. Specifically, the calculated distribution is too hot by 2--3 rotational quanta, and the predicted enhancement in the v'=1 rate with reagent vibrational excitation is too large by 67%±9

  12. Polymorphisms of CCL3L1/CCR5 genes and recurrence of hepatitis B in liver transplant recipients.

    Science.gov (United States)

    Li, Hong; Xie, Hai-Yang; Zhou, Lin; Wang, Wei-Lin; Liang, Ting-Bo; Zhang, Min; Zheng, Shu-Sen

    2011-12-01

    The genetic diversity of chemokines and chemokine receptors has been associated with the outcome of hepatitis B virus infection. The aim of this study was to evaluate whether the copy number variation in the CCL3L1 gene and the polymorphisms of CCR5Δ32 and CCR5-2459A→G (rs1799987) are associated with recurrent hepatitis B in liver transplantation for hepatitis B virus infection-related end-stage liver disease. A total of 185 transplant recipients were enrolled in this study. The genomic DNA was extracted from whole blood, the copy number of the CCL3L1 gene was determined by a quantitative real-time PCR based assay, CCR5Δ32 was detected by a sizing PCR method, and a single-nucleotide polymorphism in CCR5-2459 was detected by restriction fragment length polymorphism PCR. No CCR5Δ32 mutation was detected in any of the individuals from China. Neither copy number variation nor polymorphism in CCR5-2459 was associated with post-transplant re-infection with hepatitis B virus. However, patients with fewer copies (CCR5 genes might be more likely to have recurrence of hepatitis B after transplantation.

  13. Relationship between CCR and NT-proBNP in Chinese HF patients, and their correlations with severity of HF.

    Science.gov (United States)

    Lu, Zhigang; Wang, Bo; Wang, Yunliang; Qian, Xueqing; Zheng, Wei; Wei, Meng

    2014-01-01

    To evaluate the relationship between creatinine clearance rate (CCR) and the level of N-terminal pro-B-type natriuretic peptide (NT-proBNP) in heart failure (HF) patients and their correlations with HF severity. Two hundred and one Chinese patients were grouped according to the New York Heart Association (NYHA) classification as NYHA 1-2 and 3-4 groups and 135 cases out of heart failure patients as control group. The following variables were compared among these three groups: age, sex, body mass index (BMI), smoking status, hypertension, diabetes, NT-proBNP, creatinine (Cr), uric acid (UA), left ventricular end-diastolic diameter (LVEDD), and CCR. The biomarkers of NT-proBNP, Cr, UA, LVEDD, and CCR varied significantly in the three groups, and these variables were positively correlated with the NHYA classification. The levels of NT-proBNP and CCR were closely related to the occurrence of HF and were independent risk factors for HF. At the same time, there was a significant negative correlation between the levels of NT-proBNP and CCR. The area under the receiver operating characteristic curve suggested that the NT-proBNP and CCR have high accuracy for diagnosis of HF and have clinical diagnostic value. NT-proBNP and CCR may be important biomarkers in evaluating the severity of HF.

  14. Adaptive gain modulation in V1 explains contextual modifications during bisection learning.

    Directory of Open Access Journals (Sweden)

    Roland Schäfer

    2009-12-01

    Full Text Available The neuronal processing of visual stimuli in primary visual cortex (V1 can be modified by perceptual training. Training in bisection discrimination, for instance, changes the contextual interactions in V1 elicited by parallel lines. Before training, two parallel lines inhibit their individual V1-responses. After bisection training, inhibition turns into non-symmetric excitation while performing the bisection task. Yet, the receptive field of the V1 neurons evaluated by a single line does not change during task performance. We present a model of recurrent processing in V1 where the neuronal gain can be modulated by a global attentional signal. Perceptual learning mainly consists in strengthening this attentional signal, leading to a more effective gain modulation. The model reproduces both the psychophysical results on bisection learning and the modified contextual interactions observed in V1 during task performance. It makes several predictions, for instance that imagery training should improve the performance, or that a slight stimulus wiggling can strongly affect the representation in V1 while performing the task. We conclude that strengthening a top-down induced gain increase can explain perceptual learning, and that this top-down signal can modify lateral interactions within V1, without significantly changing the classical receptive field of V1 neurons.

  15. The effect of the CCR5-delta32 deletion on global gene expression considering immune response and inflammation

    Directory of Open Access Journals (Sweden)

    Hütter Gero

    2011-10-01

    Full Text Available Abstract Background The natural function of the C-C chemokine receptor type 5 (CCR5 is poorly understood. A 32 base pair deletion in the CCR5 gene (CCR5-delta32 located on chromosome 3 results in a non-functional protein. It is supposed that this deletion causes an alteration in T-cell response to inflammation. For example, the presence of the CCR5-delta32 allele in recipients of allografts constitutes as an independent and protective factor associated with a decreased risk of graft-versus-host disease (GVHD and graft rejection. However, the mechanism of this beneficial effect of the deletion regarding GVHD is unknown. In this survey we searched for a CCR5-delta32 associated regulation of critical genes involved in the immune response and the development of GVHD. Methods We examined CD34+ hematopoietic progenitor cells derived from bone marrow samples from 19 healthy volunteers for the CCR5-delta32 deletion with a genomic PCR using primers flanking the site of the deletion. Results 12 individuals were found to be homozygous for CCR5 WT and 7 carried the CCR5-delta32 deletion heterozygously. Global gene expression analysis led to the identification of 11 differentially regulated genes. Six of them are connected with mechanisms of immune response and control: LRG1, CXCR2, CCRL2, CD6, CD7, WD repeat domain, and CD30L. Conclusions Our data indicate that the CCR5-delta32 mutation may be associated with differential gene expression. Some of these genes are critical for immune response, in the case of CD30L probably protective in terms of GVHD.

  16. CCR6+ Th cell distribution differentiates systemic lupus erythematosus patients based on anti-dsDNA antibody status.

    Science.gov (United States)

    Zhong, Wei; Jiang, Zhenyu; Wu, Jiang; Jiang, Yanfang; Zhao, Ling

    2018-01-01

    Systemic lupus erythematosus (SLE) disease has been shown to be associated with the generation of multiple auto-antibodies. Among these, anti-dsDNA antibodies (anti-DNAs) are specific and play a pathogenic role in SLE. Indeed, anti-DNA + SLE patients display a worse disease course. The generation of these pathogenic anti-DNAs has been attributed to the interaction between aberrant T helper (Th) cells and autoimmune B cells. Thus, in this study we have investigated whether CCR6 + Th cells have the ability to differentiate SLE patients based on anti-DNA status, and if their distribution has any correlation with disease activity. We recruited 25 anti-DNA + and 25 anti-DNA - treatment-naive onset SLE patients, matched for various clinical characteristics in our nested matched case-control study. CCR6 + Th cells and their additional subsets were analyzed in each patient by flow cytometry. Anti-DNA + SLE patients specifically had a higher percentage of Th cells expressing CCR6 and CXCR3. Further analysis of CCR6 + Th cell subsets showed that anti-DNA + SLE patients had elevated proportions of Th9, Th17, Th17.1 and CCR4/CXCR3 double-negative (DN) cells. However, the proportions of CCR6 - Th subsets, including Th1 and Th2 cells, did not show any association with anti-DNA status. Finally, we identified a correlation between CCR6 + Th subsets and clinical indicators, specifically in anti-DNA + SLE patients. Our data indicated that CCR6 + Th cells and their subsets were elevated and correlated with disease activity in anti-DNA + SLE patients. We speculated that CCR6 + Th cells may contribute to distinct disease severity in anti-DNA + SLE patients.

  17. CCR8 Signaling Influences Toll-Like Receptor 4 Responses in Human Macrophages in Inflammatory Diseases ▿

    Science.gov (United States)

    Kvist Reimer, Martina; Brange, Charlotte; Rosendahl, Alexander

    2011-01-01

    CCR8 immunity is generally associated with Th2 responses in allergic diseases. In this study, we demonstrate for the first time a pronounced attenuated influx of macrophages in ovalbumin (OVA)-challenged CCR8 knockout mice. To explore whether macrophages in human inflamed lung tissue also were CCR8 positive, human lung tissue from patients with chronic obstructive pulmonary disease (COPD) was evaluated. Indeed, CCR8 expression was pronounced in invading monocytes/macrophages from lungs of patients with Global Initiative for Obstructive Lung Disease (GOLD) stage IV COPD. Given this expression pattern, the functional role of CCR8 on human macrophages was evaluated in vitro. Human peripheral blood monocytes expressed low levels of CCR8, while macrophage colony-stimulating factor (M-CSF)-derived human macrophages expressed significantly elevated surface levels of CCR8. Importantly, CCL1 directly regulated the expression of CD18 and CD49b and hence influenced the adhesion capacity of human macrophages. CCL1 drives chemotaxis in M-CSF-derived macrophages, and this could be completely inhibited by lipopolysaccharide (LPS). Whereas both CCL1 and LPS monotreatment inhibited spontaneous superoxide release in macrophages, CCL1 significantly induced superoxide release in the presence of LPS in a dose-dependent manner. Finally, CCL1 induced production of proinflammatory cytokines such as tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) and could inhibit LPS-induced cytokine production in a dose-dependent manner. Our data demonstrate, for the first time, the presence of CCR8 on inflammatory macrophages in human COPD lung tissue. Importantly, the functional data from human macrophages suggest a potential cross talk between the CCR8 and the Toll-like receptor 4 (TLR4) pathways, both of which are present in COPD patients. PMID:21976223

  18. A phase 2 clinical study of 99mTc-MAG3 injectable, a dynamic renal imaging agent

    International Nuclear Information System (INIS)

    Torizuka, Kanji; Yamamoto, Kazutaka; Nishibuchi, Shigeo; Ishibashi, Akira; Ikekubo, Katsuji.

    1993-01-01

    A phase 2 clinical study of 99m Tc-mercapto acetyl glycylglycylglycine ( 99m Tc-MAG3) injectable, a new dynamic renal imaging agent, was performed in 110 patients with renal and/or urinary disorders to evaluate the safety, efficacy and optimal dose of this agent. Neither adverse reactions nor abnormal laboratory findings due to intravenous administration of 99m Tc-MAG3 were observed. The investigators evaluated the clinical efficacy of 99m Tc-MAG3 was to be effective in 96 of 97 cases. Among the doses of 92.5 MBq, 370 MBq and 555 MBq, the dose of 92.5 MBq was not large enough to provide adequate-quality blood flow images or reliable information for evaluation of the renal blood flow. It was concluded that the optimal dose range of 99m Tc-MAG3 was 185-555 MBq with 370 MBq as the standard dose. Also, we summarize that 555 MBq is especially recommendable when detailed blood flow information is required. These results indicate that 99m Tc-MAG3 injectable is useful for the diagnosis of renal and urinary disorders. (author)

  19. PmagPy: Software Package for Paleomagnetic Data Analysis and Gateway to the Magnetics Information Consortium (MagIC) Database

    Science.gov (United States)

    Jonestrask, L.; Tauxe, L.; Shaar, R.; Jarboe, N.; Minnett, R.; Koppers, A. A. P.

    2014-12-01

    There are many data types and methods of analysis in rock and paleomagnetic investigations. The MagIC database (http://earthref.org/MAGIC) was designed to accommodate the vast majority of data used in such investigations. Yet getting data from the laboratory into the database, and visualizing and re-analyzing data downloaded from the database, makes special demands on data formatting. There are several recently published programming packages that deal with single types of data: demagnetization experiments (e.g., Lurcock et al., 2012), paleointensity experiments (e.g., Leonhardt et al., 2004), and FORC diagrams (e.g., Harrison et al., 2008). However, there is a need for a unified set of open source, cross-platform software that deals with the great variety of data types in a consistent way and facilitates importing data into the MagIC format, analyzing them and uploading them into the MagIC database. The PmagPy software package (http://earthref.org/PmagPy/cookbook/) comprises a such a comprehensive set of tools. It facilitates conversion of many laboratory formats into the common MagIC format and allows interpretation of demagnetization and Thellier-type experimental data. With some 175 programs and over 250 functions, it can be used to create a wide variety of plots and allows manipulation of downloaded data sets as well as preparation of new contributions for uploading to the MagIC database.

  20. CCR-2 neutralization augments murine fresh BMC activation by Staphylococcus aureus via two distinct mechanisms: at the level of ROS production and cytokine response.

    Science.gov (United States)

    Nandi, Ajeya; Bishayi, Biswadev

    2017-05-01

    CCR-2 signaling regulates recruitment of monocytes from the bone marrow into the bloodstream and then to sites of infection. We sought to determine whether CCL-2/CCR-2 signaling is involved in the killing of Staphylococcus aureus by murine bone marrow cells (BMCs). The intermittent link of reactive oxygen species (ROS)-NF-κB/p38-MAPK-mediated CCL-2 production in CCR-2 signaling prompted us to determine whether neutralization of CCR-2 augments the response of murine fresh BMCs (FBMCs) after S. aureus infection. It was observed that anti-CCR-2 Ab-treated FBMCs released fewer ROS on encountering S. aureus infection than CCR-2 non-neutralized FBMCs, also correlating with reduced killing of S. aureus in CCR-2 neutralized FBMCs. Staphylococcal catalase and SOD were also found to play a role in protecting S. aureus from the ROS-mediated killing of FBMC. S. aureus infection of CCR-2 intact FBMCs pre-treated with either NF-κB or p-38-MAPK blocker induced less CCL-2, suggesting that NF-κB or p-38-MAPK is required for CCL-2 production by FBMCs. Moreover, blocking of CCR-2 along with NF-κB or p-38-MAPK resulted in elevated CCL-2 production and reduced CCR-2 expression. Inhibition of CCR-2 impairs the response of murine BMCs to S. aureus infection by attenuation ROS production and modulating the cytokine response.

  1. Expression of RANTES, eotaxin-2, ICAM-1, LFA-1 and CCR-3 in chronic rhinosinusitis patients with nasal polyposis.

    Science.gov (United States)

    Cavallari, Fransérgio Emílio; Valera, Fabiana Cardoso Pereira; Gallego, Aline Jorge; Malinsky, Rafael Rossell; Küpper, Daniel Salgado; Milanezi, Cristiane; Silva, João Santana da; Tamashiro, Edwin; Anselmo-Lima, Wilma Terezinha

    2012-09-01

    To compare gene expression of the chemokines RANTES and eotaxin-2, its receptor, CCR-3, adhesion molecule ICAM-1 and its receptor LFA-1 in eosinophilic polyps and in control normal nasal mucosa. Gene expression was quantified by Real Time PCR in polyps (n=35) and in healthy nasal mucosa (n=15). Eosinophilic polyps showed a higher expression of eotaxin-2 and RANTES, but not of CCR-3, ICAM-1 or LFA-1 compared to control nasal mucosa. Eosinophilic polyps present greater expression of eotaxin-2 and RANTES, but not of CCR-3, ICAM-1 or LFA-1 compared to control nasal mucosa.

  2. Both Cerebral and Hematopoietic Deficiencies in CCR2 Result in Uncontrolled Herpes Simplex Virus Infection of the Central Nervous System in Mice.

    Science.gov (United States)

    Menasria, Rafik; Canivet, Coraline; Piret, Jocelyne; Gosselin, Jean; Boivin, Guy

    2016-01-01

    CCR2 is a chemokine receptor expressed on the surface of blood leukocytes, particularly «Ly6Chi» inflammatory monocytes and microglia. Signaling through this receptor is thought to influence the immune activity of microglia as well as monocytes egress from the bone marrow (BM) and their trafficking into the central nervous system (CNS) in several neurological diseases. During experimental herpes simplex virus 1 (HSV-1) encephalitis (HSE), CCR2 deficiency has been reported to exacerbate the outcome of the disease. However, the precise contribution of CCR2 expressed in cells of the CNS or peripheral monocytes in the protection against HSE remains unclear. To dissect the differential role of CCR2 during HSE, chimeric mice with receptor deficiency in the brain or blood cells were generated by transplanting wild-type (WT) C57BL/6 or CCR2-/- BM-derived cells in CCR2-/- (WT→CCR2-/-) and WT (CCR2-/-→WT) mice, respectively. Our results indicate that following intranasal infection with 1.2x106 plaque forming units of HSV-1, CCR2 deficiency in hematopoietic cells and, to a lesser extent, in CNS exacerbates the outcome of HSE. Mortality rates of CCR2-/- (71.4%) and CCR2-/-→WT (57.1%) mice were significantly higher than that of WT (15.3%; Pdeficiencies in CCR2 resulted in increased infectious viral titers and wider dissemination of HSV antigens in the brain as well as an overproduction of inflammatory cytokines and chemokines including IL-1β, IL-6, CCL2, CCL3 and CCL5. Furthermore, CCR2 deficiency in the hematopoietic system altered monocytes egress from the BM and their recruitment to the CNS, which may contribute to the failure in HSV-1 containment. Collectively, these data suggest that CCR2 expressed on cells of CNS and especially on peripheral monocytes is important for the control of HSV-1 replication and inflammatory environment during experimental HSE.

  3. Properties of V1 neurons tuned to conjunctions of visual features: application of the V1 saliency hypothesis to visual search behavior.

    Directory of Open Access Journals (Sweden)

    Li Zhaoping

    Full Text Available From a computational theory of V1, we formulate an optimization problem to investigate neural properties in the primary visual cortex (V1 from human reaction times (RTs in visual search. The theory is the V1 saliency hypothesis that the bottom-up saliency of any visual location is represented by the highest V1 response to it relative to the background responses. The neural properties probed are those associated with the less known V1 neurons tuned simultaneously or conjunctively in two feature dimensions. The visual search is to find a target bar unique in color (C, orientation (O, motion direction (M, or redundantly in combinations of these features (e.g., CO, MO, or CM among uniform background bars. A feature singleton target is salient because its evoked V1 response largely escapes the iso-feature suppression on responses to the background bars. The responses of the conjunctively tuned cells are manifested in the shortening of the RT for a redundant feature target (e.g., a CO target from that predicted by a race between the RTs for the two corresponding single feature targets (e.g., C and O targets. Our investigation enables the following testable predictions. Contextual suppression on the response of a CO-tuned or MO-tuned conjunctive cell is weaker when the contextual inputs differ from the direct inputs in both feature dimensions, rather than just one. Additionally, CO-tuned cells and MO-tuned cells are often more active than the single feature tuned cells in response to the redundant feature targets, and this occurs more frequently for the MO-tuned cells such that the MO-tuned cells are no less likely than either the M-tuned or O-tuned neurons to be the most responsive neuron to dictate saliency for an MO target.

  4. Properties of V1 neurons tuned to conjunctions of visual features: application of the V1 saliency hypothesis to visual search behavior.

    Science.gov (United States)

    Zhaoping, Li; Zhe, Li

    2012-01-01

    From a computational theory of V1, we formulate an optimization problem to investigate neural properties in the primary visual cortex (V1) from human reaction times (RTs) in visual search. The theory is the V1 saliency hypothesis that the bottom-up saliency of any visual location is represented by the highest V1 response to it relative to the background responses. The neural properties probed are those associated with the less known V1 neurons tuned simultaneously or conjunctively in two feature dimensions. The visual search is to find a target bar unique in color (C), orientation (O), motion direction (M), or redundantly in combinations of these features (e.g., CO, MO, or CM) among uniform background bars. A feature singleton target is salient because its evoked V1 response largely escapes the iso-feature suppression on responses to the background bars. The responses of the conjunctively tuned cells are manifested in the shortening of the RT for a redundant feature target (e.g., a CO target) from that predicted by a race between the RTs for the two corresponding single feature targets (e.g., C and O targets). Our investigation enables the following testable predictions. Contextual suppression on the response of a CO-tuned or MO-tuned conjunctive cell is weaker when the contextual inputs differ from the direct inputs in both feature dimensions, rather than just one. Additionally, CO-tuned cells and MO-tuned cells are often more active than the single feature tuned cells in response to the redundant feature targets, and this occurs more frequently for the MO-tuned cells such that the MO-tuned cells are no less likely than either the M-tuned or O-tuned neurons to be the most responsive neuron to dictate saliency for an MO target.

  5. A V1-vascular vasopressin antagonist suitable for radioiodination and photoaffinity labeling

    International Nuclear Information System (INIS)

    Thibonnier, M.; Chehade, N.; Hinko, A.

    1990-01-01

    We have previously characterized the V1-vascular arginine vasopressin (AVP) receptors of human platelets. We now report on a radiomonoiodinated and photoreactive V1-vascular AVP antagonist (V1-ag) to be used for the purification of human V1-vascular AVP receptors. The V1-ag, d(CH2)5Tyr(Me)Tyr(NH2)AVP was modified by radiomonoiodination of d(CH2)5-Tyr(Me)Tyr(NH2)AVP with the Iodogen technique, and derivatization of d(CH2)5Tyr(Me)Tyr[125I](NH2)-AVP with the photoreactive crosslinker, N-hydroxysuccinimidyl-4-azidobenzoate (HSAB) (each step included HPLC purification). In competition experiments, the affinity of these V1-ag for the human platelet AVP receptors remained excellent. Irreversible photoaffinity labeling of the platelet V1-vascular AVP receptor was successfully achieved by UV lamp exposure (365 nm, 20 min). Thus, AzBz-d(CH2)5Tyr(Me)Tyr[125I](NH2)AVP is a promising tool to use for the purification of human V1-vascular AVP receptors

  6. Different glutamate receptors convey feedforward and recurrent processing in macaque V1

    NARCIS (Netherlands)

    Self, M.W.; Kooijmans, R.N.; Super, H.; Lamme, V.A.F.; Roelfsema, P.R.

    2012-01-01

    Neurons in the primary visual cortex (V1) receive feedforward input from the thalamus, which shapes receptive-field properties. They additionally receive recurrent inputs via horizontal connections within V1 and feedback from higher visual areas that are thought to be important for conscious visual

  7. USEEIO v1.1 - Elementary Flows and Life Cycle Impact Assessment (LCIA) Characterization Factors

    Data.gov (United States)

    U.S. Environmental Protection Agency — This dataset is part of the USEEIO v1.1 model release. It provides the elementary flows used in the USEEIO v1.1 Satellite Tables (DOI: 10.23719/1365565) and their...

  8. Comparison of measurement of 99mTc-MAG3 plasma clearance by single plasma sample and renal uptake ratio

    International Nuclear Information System (INIS)

    Ushijima, Yo; Sugihara, Hiroki; Okuyama, Chio; Okitsu, Sigeyuki; Nii, Takeshi; Nishida, Takuji; Okamoto, Kunio; Maeda, Tomoho

    1997-01-01

    Measurement of 99m Tc-MAG 3 plasma clearance based on one-compartment model (MPC method) is a non-invasive method using the renal uptake ratio. We evaluated the clinical usefulness of this method, compared with effective renal plasma flow (ERPF) using 123 I-OIH and two single-plasma sample methods using 99m Tc-MAG 3 (Russell method and Bubeck method). The ratio of 99m Tc-MAG 3 clearance to ERPF was 1.00±0.26. MPC method correlated well with Russell and Bubeck methods (r=0.904, r=0.897). We conclude that MPC method is a suitable replacement for single-plasma sample method in routine clinical use. (author)

  9. Correlation between differential renal uptake of 99mTc-MAG3 and 99mTc-DMSA

    International Nuclear Information System (INIS)

    Obaldo, J.M.; Gruenwald, F.; Menzel, C.; Biersack, H.J.

    1994-01-01

    We reviewed the quantitative indices obtained from sequential 99m Tc-MAG3 and 99m Tc-DMSA imaging studies performed in 134 patients with a variety of renal disorders in order to determine the correlation between the measured differential renal function using these two agents. Overall correlation was high with r=.86 and the derived regression equation was R.F. DMSA =8.2+0.84 (R.F. MAG3 ), where F.F. is the relative function. Highly divergent values for differential function were obtained however in some subjects. Patients with renal obstructive disorders had a correlation coefficient of.81 which was lower than those with nonobstructive pathologies (r=.95). Although relative kidney function measured using 99m Tc-MAG3 and 99m Tc-DMSA correlate significantly, certain patients such as those with renal obstruction may necessitate quantitation using different renal parameters. (orig.) [de

  10. A camera based calculation of 99m Tc-MAG-3 clearance using conjugate views method

    International Nuclear Information System (INIS)

    Hojabr, M.; Rajabi, H.; Eftekhari, M.

    2004-01-01

    Background: measurement of absolute or different renal function using radiotracers plays an important role in the clinical management of various renal diseases. Gamma camera quantitative methods is approximations of renal clearance may potentially be as accurate as plasma clearance methods. However some critical factors such as kidney depth and background counts are still troublesome in the use of this technique. In this study the conjugate-view method along with some background correction technique have been used for the measurement of renal activity in 99m Tc- MAG 3 renography. Transmission data were used for attenuation correction and the source volume was considered for accurate background subtraction. Materials and methods: the study was performed in 35 adult patients referred to our department for conventional renography and ERPF calculation. Depending on patients weight approximately 10-15 mCi 99 Tc-MAG 3 was injected in the form of a sharp bolus and 60 frames of 1 second followed by 174 frames of 10 seconds were acquired for each patient. Imaging was performed on a dual-head gamma camera(SOLUS; SunSpark10, ADAC Laboratories, Milpitas, CA) anterior and posterior views were acquired simultaneously. A LEHR collimator was used to correct the scatter for the emission and transmission images. Buijs factor was applied on background counts before background correction (Rutland-Patlak equation). gamma camera clearance was calculated using renal uptake in 1-2, 1.5-2.5, 2-3 min. The same procedure was repeated for both renograms obtained from posterior projection and conjugated views. The plasma clearance was also directly calculated by three blood samples obtained at 40, 80, 120 min after injection. Results: 99 Tc-MAG 3 clearance using direct sampling method were used as reference values and compared to the results obtained from the renograms. The maximum correlation was found between conjugate view clearance at 2-3 min (R=0.99, R 2 =0.98, SE=15). Conventional

  11. Monocytes infiltrate the pancreas via the MCP-1/CCR2 pathway and differentiate into stellate cells.

    Directory of Open Access Journals (Sweden)

    Kazuko Ino

    Full Text Available Recent studies have shown that monocytes possess pluripotent plasticity. We previously reported that monocytes could differentiate into hepatic stellate cells. Although stellate cells are also present in the pancreas, their origin remains unclear. An accumulation of enhanced green fluorescent protein (EGFP(+CD45(- cells was observed in the pancreases and livers of chimeric mice, which were transplanted with a single hematopoietic stem cell isolated from EGFP-transgenic mice and treated with carbon tetrachloride (CCl4. Because the vast majority of EGFP(+CD45(- cells in the pancreas expressed stellate cell-associated antigens such as vimentin, desmin, glial fibrillary acidic protein, procollagen-I, and α-smooth muscle actin, they were characterized as pancreatic stellate cells (PaSCs. EGFP(+ PaSCs were also observed in CCl4-treated mice adoptively transferred with monocytes but not with other cell lineages isolated from EGFP-transgenic mice. The expression of monocyte chemoattractant protein-1 (MCP-1 and angiotensin II (Ang II increased in the pancreas of CCl4-treated mice and their respective receptors, C-C chemokine receptor 2 (CCR2 and Ang II type 1 receptor (AT1R, were expressed on Ly6C(high monocytes isolated from EGFP-transgenic mice. We examined the effect of an AT1R antagonist, irbesartan, which is also a CCR2 antagonist, on the migration of monocytes into the pancreas. Monocytes migrated toward MCP-1 but not Ang II in vitro. Irbesartan inhibited not only their in vitro chemotaxis but also in vivo migration of adoptively transferred monocytes from peripheral blood into the pancreas. Irbesartan treatment significantly reduced the numbers of EGFP(+F4/80(+CCR2(+ monocytic cells and EGFP(+ PaSCs in the pancreas of CCl4-treated chimeric mice receiving EGFP(+ bone marrow cells. A specific CCR2 antagonist RS504393 inhibited the occurrence of EGFP(+ PaSCs in injured mice. We propose that CCR2(+ monocytes migrate into the pancreas possibly via the

  12. HIV-infected individuals with the CCR delta32/CCR5 genotype have lower HIV RNA levels and higher CD4 cell counts in the early years of the infection than do patients with the wild type. Copenhagen AIDS Cohort Study Group

    DEFF Research Database (Denmark)

    Katzenstein, T L; Eugen-Olsen, J; Hofmann, B

    1997-01-01

    The relations among serum HIV RNA levels, CD4 cell counts, presence of the mutant CCR5-allele in heterozygous form, and clinical outcome was analyzed in 96 patients from the Copenhagen AIDS Cohort. In the early years of the infection, patients with the CCR5 delta32/CCR5 genotype had significantly...

  13. First industrial application of MAG STT welding with auto adaptative joint control

    International Nuclear Information System (INIS)

    Tran Tien, Thong

    2006-01-01

    The Welding Institute has participated to an extraordinary plan: the manufacture of the new LHC (Large Hadron Collider) particles accelerator in a circular tunnel of 27 km of circumference, at the European laboratory for particles physics (CERN) located at the Franco-Swiss frontier. The LHC dipolar magnets wires constituted in semi-cylinders of 15 m length in 316 LN, thickness 10 mm, are assembled in horizontal-vertical position. The Welding Institute has developed a software allowing to implement the auto-adaptative welding with follow of laser joint, using the MAG STT (Surface Tension Transfer) process. The modeling of welding laws connected with the strategy of joints filling runs (in multi-passes), absorb the physical tolerances of the preparation (clearance, poor alignment, root of joint...) and this in welding dynamical condition. (O.M.)

  14. First industrial application of the auto-adaptative MAG STT welding technique with laser joint tracking

    International Nuclear Information System (INIS)

    Tran Tien, Th.

    2007-01-01

    The Welding Institute has participated to the plan of construction of the Large Hadron Collider. The hoops of the dipolar magnets are composed of two half cylinders 15 m in length in 10 mm 316LN austenitic stainless steel and are assembled around the magnet in a horizontal-vertical position. The Welding Institute has developed a software for carrying out the auto-adaptative welding technique with laser joint tracking, in using the MAG STT (Surface Tension Transfer) process. The modelling of the welding laws and the strategy of filling the joints in multi-paths absorb the physical tolerances of the preparation (clearance, poor alignment, root..) in dynamic welding condition too. (O.M.)

  15. MagLIF Pre-Heat Optimization on the PECOS Surrogacy Platform

    Science.gov (United States)

    Geissel, Matthias; Harvey-Thompson, A. J.; Ampleford, D.; Awe, T. J.; Bliss, D. E.; Glinsky, M. E.; Gomez, M. R.; Harding, E.; Hansen, S. B.; Jennings, C.; Kimmel, M. W.; Knapp, P. F.; Lewis, S. M.; Peterson, K.; Rochau, G. A.; Schollmeier, M.; Schwarz, J.; Shores, J. E.; Slutz, S. A.; Sinars, D. B.; Smith, I. C.; Speas, C. S.; Vesey, R. A.; Weis, M. R.; Porter, J. L.

    2017-10-01

    Sandia's MagLIF Program is using the PECOS target area as a platform to optimize the coupling of laser energy into the fuel. After developing laser pulse shapes that reduced SBS and improved energy deposition (presented last year), we will report on the effect on integrated experiments with Z. Despite encouraging results, questions remained about the equivalency of He, (PECOS studies), versus D2 (Z). Furthermore, simulations imply that the goal of at least 1 kJ in the fuel will require higher pressures, requiring a re-design of the gas delivery system. We will present recent results for backscatter measurements and energy deposition profiles in 60 psi and 90 psi deuterium fills and compare them to previously studied helium fills. Sandia National Labs is managed and operated by National Technology and Engineering Solutions of Sandia, LLC., a subsidiary of Honeywell International, Inc., for U.S. DoE/NNSA under contract DE-NA0003525.

  16. Preparation of magnetic carbon nanotubes (Mag-CNTs) for biomedical and biotechnological applications.

    Science.gov (United States)

    Masotti, Andrea; Caporali, Andrea

    2013-12-18

    Carbon nanotubes (CNTs) have been widely studied for their potential applications in many fields from nanotechnology to biomedicine. The preparation of magnetic CNTs (Mag-CNTs) opens new avenues in nanobiotechnology and biomedical applications as a consequence of their multiple properties embedded within the same moiety. Several preparation techniques have been developed during the last few years to obtain magnetic CNTs: grafting or filling nanotubes with magnetic ferrofluids or attachment of magnetic nanoparticles to CNTs or their polymeric coating. These strategies allow the generation of novel versatile systems that can be employed in many biotechnological or biomedical fields. Here, we review and discuss the most recent papers dealing with the preparation of magnetic CNTs and their application in biomedical and biotechnological fields.

  17. Multi-Objective data analysis using Bayesian Inference for MagLIF experiments

    Science.gov (United States)

    Knapp, Patrick; Glinksy, Michael; Evans, Matthew; Gom, Matth; Han, Stephanie; Harding, Eric; Slutz, Steve; Hahn, Kelly; Harvey-Thompson, Adam; Geissel, Matthias; Ampleford, David; Jennings, Christopher; Schmit, Paul; Smith, Ian; Schwarz, Jens; Peterson, Kyle; Jones, Brent; Rochau, Gregory; Sinars, Daniel

    2017-10-01

    The MagLIF concept has recently demonstrated Gbar pressures and confinement of charged fusion products at stagnation. We present a new analysis methodology that allows for integration of multiple diagnostics including nuclear, x-ray imaging, and x-ray power to determine the temperature, pressure, liner areal density, and mix fraction. A simplified hot-spot model is used with a Bayesian inference network to determine the most probable model parameters that describe the observations while simultaneously revealing the principal uncertainties in the analysis. Sandia National Laboratories is a multimission laboratory managed and operated by National Technology and Engineering Solutions of Sandia, LLC., a wholly owned subsidiary of Honeywell International, Inc., for the U.S. Department of Energy's National Nuclear Security Administration under contract DE-NA-0003525.

  18. Neutron activation analysis of the MIBI, MAG-3 and sodium fitate active principles

    International Nuclear Information System (INIS)

    Capote Rodriguez, G.; Perez Sayaz, G.; Moreno Bermudez, J.; Ribeiro Guevara, S.; Molina Insfran, J.

    1996-01-01

    Neutron activation analysis (NAA) both instrumental (INAA) and radiochemical (RNAA) are extensively applied for determination of minor and trace elements in samples of quite different origin and composition. Particularly, the application of INAA is well recognized for analysis of microquantitis of heavy metals as well as toxic elements in biological samples. In this work the possibility of the determination of MIBI, MAG-3 and sodium fitate elemental composition by INAA was investigated Analytical information about the concentration and/or detection limits of some toxic elements (Hg, Cd, As, Se, Sb) and other trace elements of interest (Fe, Cr, Co, Zn, Br) was obtained. The samples were irradiated in the CAb Ra-6 nuclear research reactor

  19. The impact of CCR5-Δ32 deletion on C-reactive protein levels and cardiovascular disease

    DEFF Research Database (Denmark)

    Dinh, Khoa Manh; Pedersen, Ole B; Petersen, Mikkel S

    2015-01-01

    BACKGROUND AND PURPOSE: The C-C chemokine receptor 5-Δ32 deletion (CCR5-Δ32) has been associated with lower levels of C-reactive protein (CRP), but the effect on cardiovascular diseases is uncertain. This study addresses the impact of CCR5-Δ32 on the risk of low-grade inflammation...... and hospitalization with cardiovascular diseases in a large cohort of blood donors. METHODS: Genotyping of 15,206 healthy participants from The Danish Blood Donor Study for CCR5-Δ32 was performed and combined with CRP measurements and questionnaire data. Cardiovascular disease diagnoses were identified by ICD-10......: In this cohort, carriers of the CCR5-Δ32 deletion had normal CRP levels but a borderline significant increased risk of cardiovascular diseases....

  20. MAG narrow gap welding - an economic way to minimize welding expenses

    International Nuclear Information System (INIS)

    Kast, W.; Scholz, E.; Weyland, F.

    1982-01-01

    The thicker structural components are, the more important it is to take measures to reduce the volume of the weld. The welding process requiring the smallest possible weld section is the so-called narrow gap process. In submerged arc narrow gap welding as well as in MAG narrow gap welding different variants are imaginable, some of them already in practical use. With regard to efficiency and weld quality an optimum variant of the MAG narrow gap welding process is described. It constitutes a two wire system in which two wire electrodes of 1.2 mm diameter are arranged one behind the other. In order to avoid lack of fusion, the wire guides are slightly pointed towards each groove face. Thus, by inclining the two arcs burning one behind the other in the direction of weld progress, it is achieved that two separately solidifying weld pools and two beads per layer are simultaneously formed. Welding parameters are selected in such a way that a heat input of 16-20 kJ/cm and a deposition rate of 11-16 kgs/h are obtained. In spite of this comparatively high deposition rate, good impact values are found both in the weld and HAZ (largely reduced coarse-grain zone) which is due to an optimum weld build-up. With the available welding equipment the process can be applied to structural members having a thickness of 40-400 mm. The width of gap is 13 mm (root section) with a bevel angle of 1 0 . As filler metal, basic flux-cored wires are used which, depending on the base metal to be welded and the required tensile properties, can be of the Mn-, MnMo-, MnCrMo-, MnNi-, or MnNiMo-alloyed types. (orig.)

  1. CCR6 is expressed on an IL-10-producing, autoreactive memory T cell population with context-dependent regulatory function.

    Science.gov (United States)

    Rivino, Laura; Gruarin, Paola; Häringer, Barbara; Steinfelder, Svenja; Lozza, Laura; Steckel, Bodo; Weick, Anja; Sugliano, Elisa; Jarrossay, David; Kühl, Anja A; Loddenkemper, Christoph; Abrignani, Sergio; Sallusto, Federica; Lanzavecchia, Antonio; Geginat, Jens

    2010-03-15

    Interleukin (IL)-10 produced by regulatory T cell subsets is important for the prevention of autoimmunity and immunopathology, but little is known about the phenotype and function of IL-10-producing memory T cells. Human CD4(+)CCR6(+) memory T cells contained comparable numbers of IL-17- and IL-10-producing cells, and CCR6 was induced under both Th17-promoting conditions and upon tolerogenic T cell priming with transforming growth factor (TGF)-beta. In normal human spleens, the majority of CCR6(+) memory T cells were in the close vicinity of CCR6(+) myeloid dendritic cells (mDCs), and strikingly, some of them were secreting IL-10 in situ. Furthermore, CCR6(+) memory T cells produced suppressive IL-10 but not IL-2 upon stimulation with autologous immature mDCs ex vivo, and secreted IL-10 efficiently in response to suboptimal T cell receptor (TCR) stimulation with anti-CD3 antibodies. However, optimal TCR stimulation of CCR6(+) T cells induced expression of IL-2, interferon-gamma, CCL20, and CD40L, and autoreactive CCR6(+) T cell lines responded to various recall antigens. Notably, we isolated autoreactive CCR6(+) T cell clones with context-dependent behavior that produced IL-10 with autologous mDCs alone, but that secreted IL-2 and proliferated upon stimulation with tetanus toxoid. We propose the novel concept that a population of memory T cells, which is fully equipped to participate in secondary immune responses upon recognition of a relevant recall antigen, contributes to the maintenance of tolerance under steady-state conditions.

  2. Partial protective effect of CCR5-Delta 32 heterozygosity in a cohort of heterosexual Italian HIV-1 exposed uninfected individuals

    Directory of Open Access Journals (Sweden)

    Cauda Roberto

    2006-09-01

    Full Text Available Abstract Despite multiple sexual exposure to HIV-1 virus, some individuals remain HIV-1 seronegative (exposed seronegative, ESN. The mechanisms underlying this resistance remain still unclear, although a multifactorial pathogenesis can be hypothesised. Although several genetic factors have been related to HIV-1 resistance, the homozigosity for a mutation in CCR5 gene (the 32 bp deletion, i.e. CCR5-Delta32 allele is presently considered the most relevant one. In the present study we analysed the genotype at CCR5 locus of 30 Italian ESN individuals (case group who referred multiple unprotected heterosexual intercourse with HIV-1 seropositive partner(s, for at least two years. One hundred and twenty HIV-1 infected patients and 120 individuals representative of the general population were included as control groups. Twenty percent of ESN individuals had heterozygous CCR5-Delta 32 genotype, compared to 7.5% of HIV-1 seropositive and 10% of individuals from the general population, respectively. None of the analysed individuals had CCR5-Delta 32 homozygous genotype. Sequence analysis of the entire open reading frame of CCR5 was performed in all ESN subjects and no polymorphisms or mutations were identified. Moreover, we determined the distribution of C77G variant in CD45 gene, which has been previously related to HIV-1 infection susceptibility. The frequency of the C77G variant showed no significant difference between ESN subjects and the two control groups. In conclusion, our data show a significantly higher frequency of CCR5-Delta 32 heterozygous genotype (p = 0.04 among the Italian heterosexual ESN individuals compared to HIV-1 seropositive patients, suggesting a partial protective role of CCR5-Delta 32 heterozygosity in this cohort.

  3. A rhodanine derivative CCR-11 inhibits bacterial proliferation by inhibiting the assembly and GTPase activity of FtsZ.

    Science.gov (United States)

    Singh, Parminder; Jindal, Bhavya; Surolia, Avadhesha; Panda, Dulal

    2012-07-10

    A perturbation of FtsZ assembly dynamics has been shown to inhibit bacterial cytokinesis. In this study, the antibacterial activity of 151 rhodanine compounds was assayed using Bacillus subtilis cells. Of 151 compounds, eight strongly inhibited bacterial proliferation at 2 μM. Subsequently, we used the elongation of B. subtilis cells as a secondary screen to identify potential FtsZ-targeted antibacterial agents. We found that three compounds significantly increased bacterial cell length. One of the three compounds, namely, CCR-11 [(E)-2-thioxo-5-({[3-(trifluoromethyl)phenyl]furan-2-yl}methylene)thiazolidin-4-one], inhibited the assembly and GTPase activity of FtsZ in vitro. CCR-11 bound to FtsZ with a dissociation constant of 1.5 ± 0.3 μM. A docking analysis indicated that CCR-11 may bind to FtsZ in a cavity adjacent to the T7 loop and that short halogen-oxygen, H-bonding, and hydrophobic interactions might be important for the binding of CCR-11 with FtsZ. CCR-11 inhibited the proliferation of B. subtilis cells with a half-maximal inhibitory concentration (IC(50)) of 1.2 ± 0.2 μM and a minimal inhibitory concentration of 3 μM. It also potently inhibited proliferation of Mycobacterium smegmatis cells. Further, CCR-11 perturbed Z-ring formation in B. subtilis cells; however, it neither visibly affected nucleoid segregation nor altered the membrane integrity of the cells. CCR-11 inhibited HeLa cell proliferation with an IC(50) value of 18.1 ± 0.2 μM (∼15 × IC(50) of B. subtilis cell proliferation). The results suggested that CCR-11 inhibits bacterial cytokinesis by inhibiting FtsZ assembly, and it can be used as a lead molecule to develop FtsZ-targeted antibacterial agents.

  4. Tolerability and efficacy of inhaled AZD4818, a CCR1 antagonist, in moderate to severe COPD patients

    DEFF Research Database (Denmark)

    Kerstjens, Huib A; Bjermer, Leif; Eriksson, Leif

    2010-01-01

    OBJECTIVE: This study evaluated the tolerability and efficacy of inhaled AZD4818, a CCR1 antagonist, in patients with COPD. METHODS: This double-blind, placebo-controlled study (NCT00629239) randomised patients with moderate to severe COPD to AZD4818 300mug or placebo twice daily via Turbuhaler....... These findings in COPD are in line with other studies reporting a lack of clinical efficacy with CCR1 antagonists in other therapy areas....

  5. Interaction between NANOS2 and the CCR4-NOT Deadenylation Complex Is Essential for Male Germ Cell Development in Mouse

    OpenAIRE

    Suzuki, Atsushi; Saba, Rie; Miyoshi, Kei; Morita, Yoshinori; Saga, Yumiko

    2012-01-01

    Nanos is one of the evolutionarily conserved proteins implicated in germ cell development and we have previously shown that it interacts with the CCR4-NOT deadenylation complex leading to the suppression of specific RNAs. However, the molecular mechanism and physiological significance of this interaction have remained elusive. In our present study, we identify CNOT1, a component of the CCR4-NOT deadenylation complex, as a direct factor mediating the interaction with NANOS2. We find that the f...

  6. CCR2 deficiency leads to increased eosinophils, alternative macrophage activation, and type 2 cytokine expression in adipose tissue.

    Science.gov (United States)

    Bolus, W Reid; Gutierrez, Dario A; Kennedy, Arion J; Anderson-Baucum, Emily K; Hasty, Alyssa H

    2015-10-01

    Adipose tissue (AT) inflammation during obesity is mediated by immune cells and closely correlates with systemic insulin resistance. In lean AT, eosinophils are present in low but significant numbers and capable of promoting alternative macrophage activation in an IL-4/IL-13-dependent manner. In WT mice, obesity causes the proportion of AT eosinophils to decline, concomitant with inflammation and classical activation of AT macrophages. In this study, we show that CCR2 deficiency leads to increased eosinophil accumulation in AT. Furthermore, in contrast to WT mice, the increase in eosinophils in CCR2(-/-) AT is sustained and even amplified during obesity. Interestingly, a significant portion of eosinophils is found in CLSs in AT of obese CCR2(-/-) mice, which is the first time eosinophils have been shown to localize to these inflammatory hot spots. CCR2(-/-) bone marrow precursors displayed increased expression of various key eosinophil genes during in vitro differentiation to eosinophils, suggesting a potentially altered eosinophil phenotype in the absence of CCR2. In addition, the proportion of eosinophils in AT positively correlated with local expression of Il5, a potent eosinophil stimulator. The increase in eosinophils in CCR2(-/-) mice was detected in all white fat pads analyzed and in the peritoneal cavity but not in bone marrow, blood, spleen, or liver. In AT of CCR2(-/-) mice, an increased eosinophil number positively correlated with M2-like macrophages, expression of the Treg marker Foxp3, and type 2 cytokines, Il4, Il5, and Il13. This is the first study to link CCR2 function with regulation of AT eosinophil accumulation. © Society for Leukocyte Biology.

  7. Translational Capacity of a Cell Is Determined during Transcription Elongation via the Ccr4-Not Complex

    Directory of Open Access Journals (Sweden)

    Ishaan Gupta

    2016-05-01

    Full Text Available The current understanding of gene expression considers transcription and translation to be independent processes. Challenging this notion, we found that translation efficiency is determined during transcription elongation through the imprinting of mRNAs with Not1, the central scaffold of the Ccr4-Not complex. We determined that another subunit of the complex, Not5, defines Not1 binding to specific mRNAs, particularly those produced from ribosomal protein genes. This imprinting mechanism specifically regulates ribosomal protein gene expression, which in turn determines the translational capacity of cells. We validate our model by SILAC and polysome profiling experiments. As a proof of concept, we demonstrate that enhanced translation compensates for transcriptional elongation stress. Taken together, our data indicate that in addition to defining mRNA stability, components of the Ccr4-Not imprinting complex regulate RNA translatability, thus ensuring global gene expression homeostasis.

  8. Molecular Evolutionary Characterization of a V1R Subfamily Unique to Strepsirrhine Primates

    Science.gov (United States)

    Yoder, Anne D.; Chan, Lauren M.; dos Reis, Mario; Larsen, Peter A.; Campbell, C. Ryan; Rasoloarison, Rodin; Barrett, Meredith; Roos, Christian; Kappeler, Peter; Bielawski, Joseph; Yang, Ziheng

    2014-01-01

    Vomeronasal receptor genes have frequently been invoked as integral to the establishment and maintenance of species boundaries among mammals due to the elaborate one-to-one correspondence between semiochemical signals and neuronal sensory inputs. Here, we report the most extensive sample of vomeronasal receptor class 1 (V1R) sequences ever generated for a diverse yet phylogenetically coherent group of mammals, the tooth-combed primates (suborder Strepsirrhini). Phylogenetic analysis confirms our intensive sampling from a single V1R subfamily, apparently unique to the strepsirrhine primates. We designate this subfamily as V1Rstrep. The subfamily retains extensive repertoires of gene copies that descend from an ancestral gene duplication that appears to have occurred prior to the diversification of all lemuriform primates excluding the basal genus Daubentonia (the aye-aye). We refer to the descendent clades as V1Rstrep-α and V1Rstrep-β. Comparison of the two clades reveals different amino acid compositions corresponding to the predicted ligand-binding site and thus potentially to altered functional profiles between the two. In agreement with previous studies of the mouse lemur (genus, Microcebus), the majority of V1Rstrep gene copies appear to be intact and under strong positive selection, particularly within transmembrane regions. Finally, despite the surprisingly high number of gene copies identified in this study, it is nonetheless probable that V1R diversity remains underestimated in these nonmodel primates and that complete characterization will be limited until high-coverage assembled genomes are available. PMID:24398377

  9. Renal scintigraphy in the 21st Century 99m Tc-MAG3 with zero time injection of furosemide (MAG3-F0): a fast and easy protocol, one for all indications. Part 2. Introduction

    International Nuclear Information System (INIS)

    Sfakianakis, G.N.

    2007-01-01

    Current research on renal function to develop a method to calculate from the MAG 3 -F 0 study the renal global function (RGF) we use: a) the kidney uptake/body background activity (at 2 minutes), b) the residual cortical activity (at 20 minutes). Both these parameters are related with the creatinine levels. (Author)

  10. Lack of CCR5 modifies glial phenotypes and population of the nigral dopaminergic neurons, but not MPTP-induced dopaminergic neurodegeneration.

    Science.gov (United States)

    Choi, Dong-Young; Lee, Myung Koo; Hong, Jin Tae

    2013-01-01

    Constitutive expression of C-C chemokine receptor (CCR) 5 has been detected in astrocytes, microglia and neurons, but its physiological roles in the central nervous system are obscure. The bidirectional interactions between neuron and glial cells through CCR5 and its ligands were thought to be crucial for maintaining normal neuronal activities. No study has described function of CCR5 in the dopaminergic neurodegeneration in Parkinson's disease. In order to examine effects of CCR5 on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced dopaminergic neurodegeneration, we employed CCR5 wild type (WT) and knockout (KO) mice. Immunostainings for tyrosine hydroxylase (TH) exhibited that CCR5 KO mice had lower number of TH-positive neurons even in the absence of MPTP. Difference in MPTP (15mg/kg×4 times, 2hr interval)-mediated loss of TH-positive neurons was subtle between CCR5 WT and KO mice, but there was larger dopamine depletion, behavioral impairments and microglial activation in CCR5 deficient mice. Intriguingly, CCR5 KO brains contained higher immunoreactivity for monoamine oxidase (MAO) B which was mainly localized within astrocytes. In agreement with upregulation of MAO B, concentration of MPP+ was higher in the substantia nigra and striatum of CCR5 KO mice after MPTP injection. We found remarkable activation of p38 MAPK in CCR5 deficient mice, which positively regulates MAO B expression. These results indicate that CCR5 deficiency modifies the nigrostriatal dopaminergic neuronal system and bidirectional interaction between neurons and glial cells via CCR5 might be important for dopaminergic neuronal survival. Copyright © 2012 Elsevier Inc. All rights reserved.

  11. Ciguatoxins Evoke Potent CGRP Release by Activation of Voltage-Gated Sodium Channel Subtypes NaV1.9, NaV1.7 and NaV1.1

    Directory of Open Access Journals (Sweden)

    Filip Touska

    2017-08-01

    Full Text Available Ciguatoxins (CTXs are marine toxins that cause ciguatera fish poisoning, a debilitating disease dominated by sensory and neurological disturbances that include cold allodynia and various painful symptoms as well as long-lasting pruritus. Although CTXs are known as the most potent mammalian sodium channel activator toxins, the etiology of many of its neurosensory symptoms remains unresolved. We recently described that local application of 1 nM Pacific Ciguatoxin-1 (P-CTX-1 into the skin of human subjects induces a long-lasting, painful axon reflex flare and that CTXs are particularly effective in releasing calcitonin-gene related peptide (CGRP from nerve terminals. In this study, we used mouse and rat skin preparations and enzyme-linked immunosorbent assays (ELISA to study the molecular mechanism by which P-CTX-1 induces CGRP release. We show that P-CTX-1 induces CGRP release more effectively in mouse as compared to rat skin, exhibiting EC50 concentrations in the low nanomolar range. P-CTX-1-induced CGRP release from skin is dependent on extracellular calcium and sodium, but independent from the activation of various thermosensory transient receptor potential (TRP ion channels. In contrast, lidocaine and tetrodotoxin (TTX reduce CGRP release by 53–75%, with the remaining fraction involving L-type and T-type voltage-gated calcium channels (VGCC. Using transgenic mice, we revealed that the TTX-resistant voltage-gated sodium channel (VGSC NaV1.9, but not NaV1.8 or NaV1.7 alone and the combined activation of the TTX-sensitive VGSC subtypes NaV1.7 and NaV1.1 carry the largest part of the P-CTX-1-caused CGRP release of 42% and 34%, respectively. Given the contribution of CGRP to nociceptive and itch sensing pathways, our findings contribute to a better understanding of sensory symptoms of acute and chronic ciguatera that may help in the identification of potential therapeutics.

  12. Ciguatoxins Evoke Potent CGRP Release by Activation of Voltage-Gated Sodium Channel Subtypes NaV1.9, NaV1.7 and NaV1.1

    Science.gov (United States)

    Touska, Filip; Sattler, Simon; Malsch, Philipp; Lewis, Richard J.; Zimmermann, Katharina

    2017-01-01

    Ciguatoxins (CTXs) are marine toxins that cause ciguatera fish poisoning, a debilitating disease dominated by sensory and neurological disturbances that include cold allodynia and various painful symptoms as well as long-lasting pruritus. Although CTXs are known as the most potent mammalian sodium channel activator toxins, the etiology of many of its neurosensory symptoms remains unresolved. We recently described that local application of 1 nM Pacific Ciguatoxin-1 (P-CTX-1) into the skin of human subjects induces a long-lasting, painful axon reflex flare and that CTXs are particularly effective in releasing calcitonin-gene related peptide (CGRP) from nerve terminals. In this study, we used mouse and rat skin preparations and enzyme-linked immunosorbent assays (ELISA) to study the molecular mechanism by which P-CTX-1 induces CGRP release. We show that P-CTX-1 induces CGRP release more effectively in mouse as compared to rat skin, exhibiting EC50 concentrations in the low nanomolar range. P-CTX-1-induced CGRP release from skin is dependent on extracellular calcium and sodium, but independent from the activation of various thermosensory transient receptor potential (TRP) ion channels. In contrast, lidocaine and tetrodotoxin (TTX) reduce CGRP release by 53–75%, with the remaining fraction involving L-type and T-type voltage-gated calcium channels (VGCC). Using transgenic mice, we revealed that the TTX-resistant voltage-gated sodium channel (VGSC) NaV1.9, but not NaV1.8 or NaV1.7 alone and the combined activation of the TTX-sensitive VGSC subtypes NaV1.7 and NaV1.1 carry the largest part of the P-CTX-1-caused CGRP release of 42% and 34%, respectively. Given the contribution of CGRP to nociceptive and itch sensing pathways, our findings contribute to a better understanding of sensory symptoms of acute and chronic ciguatera that may help in the identification of potential therapeutics. PMID:28867800

  13. CCR2 and CD44 promote inflammatory cell recruitment during fatty liver formation in a lithogenic diet fed mouse model.

    Directory of Open Access Journals (Sweden)

    Charlotte E Egan

    Full Text Available Non-alcoholic fatty liver disease (NAFLD is a common disease with a spectrum of presentations. The current study utilized a lithogenic diet model of NAFLD. The diet was fed to mice that are either resistant (AKR or susceptible (BALB/c and C57BL/6 to hepatitis followed by molecular and flow cytometric analysis. Following this, a similar approach was taken in congenic mice with specific mutations in immunological genes. The initial study identified a significant and profound increase in multiple ligands for the chemokine receptor CCR2 and an increase in CD44 expression in susceptible C57BL/6 (B6 but not resistant AKR mice. Ccr2(-/- mice were completely protected from hepatitis and Cd44(-/- mice were partially protected. Despite protection from inflammation, both strains displayed similar histological steatosis scores and significant increases in serum liver enzymes. CD45(+CD44(+ cells bound to hyaluronic acid (HA in diet fed B6 mice but not Cd44(-/- or Ccr2(-/- mice. Ccr2(-/- mice displayed a diminished HA binding phenotype most notably in monocytes, and CD8(+ T-cells. In conclusion, this study demonstrates that absence of CCR2 completely and CD44 partially reduces hepatic leukocyte recruitment. These data also provide evidence that there are multiple redundant CCR2 ligands produced during hepatic lipid accumulation and describes the induction of a strong HA binding phenotype in response to LD feeding in some subsets of leukocytes from susceptible strains.

  14. Interleukin 4 increases CCR9 expression and homing of lymphocytes to gut-associated lymphoid tissue in chickens.

    Science.gov (United States)

    Annamalai, Thavamathi; Selvaraj, Ramesh K

    2012-01-15

    The effects of in vitro and in vivo IL-4 supplementation on thymocyte and splenocyte CCR9 mRNA amount and migration were studied. Thymocytes, splenocytes, splenocytes+thymocytes (2:1), and splenocytes+bursocyte cells (2:1) were supplemented with either 0 or 5 ng/ml IL-4 for 5d. CCR9 mRNA was undetectable in all experimental groups supplemented with 0 ng/ml IL-4. IL-4 treatment (5 ng/ml) upregulated (P=0.01) CCR9 mRNA only in the splenocyte+thymocyte cell culture. IL-4-mediated CCR9 mRNA induction in the splenocyte+thymocyte cell culture was dependent on the in vitro dose of IL-4 supplementation. IL-4-treated splenocyte+thymocyte cells when injected in vivo preferentially migrated to cecal tonsils. In vivo supplementation of IL-4 was achieved through in ovo injection of recombinant chicken IL-4 plasmid. Cecal tonsils in chicks hatched from IL-4-plasmid-injected eggs weighed more, had a higher amount of CCR9 mRNA, and had a higher percentage of CD8(+) cells than cecal tonsils from chicks hatched from PBS-injected eggs. It could be concluded that IL-4 induces CCR9 mRNA in thymocytes and splenocytes and directs the migration of cells to gut-associated lymphoid tissue. Copyright © 2011 Elsevier B.V. All rights reserved.

  15. The Increased Expression of CCL20 and CCR6 in Rectal Mucosa Correlated to Severe Inflammation in Pediatric Ulcerative Colitis

    Directory of Open Access Journals (Sweden)

    Keiichi Uchida

    2015-01-01

    Full Text Available Background/Aims. The aim of this study is to clarify the differences of CCL20 and CCR6 expression, chemokine correlated to intestinal homeostasis, between pediatric and adult ulcerative colitis (UC patients. Methods. Onehundred forty-one patients who underwent proctocolectomy were divided to two groups including childhood-onset UC (CUC, <16 years old, n=24 and adult-onset UC (AUC, ≧16 years old, n=117. A total of 141 formalin-fixed, paraffin-embedded tissue samples of rectum were obtained from these patients. Histological inflammation of rectum in resected specimen was evaluated by using Geboes histological assessment. In immunohistochemistry study, the CCL20 expression was evaluated by intensity and the stained area, and the CCR6 expression was evaluated by lymphocytes infiltration pattern. Results. CCL20 score and CCR6 positive lymphocytes infiltration pattern were statistically significantly correlated with histological inflammation severity of UC in all patients (P<0.05. CCL20 and CCR6 expression in CUC were statistically significantly higher than that in AUC in all or pathologically severe cases (P<0.05. Conclusions. CCL20 and CCR6 may play a significant role in local damage and pathological changes in UC especially pediatric patients. In the future, our understanding of the differences in CCL-CCR6 interaction between adults and children may lead to the pathogenesis of IBD.

  16. Inflammatory monocytes promote progression of Duchenne muscular dystrophy and can be therapeutically targeted via CCR2

    OpenAIRE

    Mojumdar, Kamalika; Liang, Feng; Giordano, Christian; Lemaire, Christian; Danialou, Gawiyou; Okazaki, Tatsuma; Bourdon, Johanne; Rafei, Moutih; Galipeau, Jacques; Divangahi, Maziar; Petrof, Basil J

    2014-01-01

    Myofiber necrosis and fibrosis are hallmarks of Duchenne muscular dystrophy (DMD), leading to lethal weakness of the diaphragm. Macrophages (MPs) are required for successful muscle regeneration, but the role of inflammatory monocyte (MO)-derived MPs in either promoting or mitigating DMD is unclear. We show that DMD (mdx) mouse diaphragms exhibit greatly increased expression of CCR2 and its chemokine ligands, along with inflammatory (Ly6Chigh) MO recruitment and accumulation of CD11bhigh MO-de...

  17. HIV-1 tropism testing and clinical management of CCR5 antagonists: Quebec review and recommendations.

    Science.gov (United States)

    Tremblay, Cécile; Hardy, Isabelle; Lalonde, Richard; Trottier, Benoit; Tsarevsky, Irina; Vézina, Louis-Philippe; Roger, Michel; Wainberg, Mark; Baril, Jean-Guy

    2013-01-01

    HIV-1 tropism assays play a crucial role in determining the response to CCR5 receptor antagonists. Initially, phenotypic tests were used, but limited access to these tests prompted the development of alternative strategies. Recently, genotyping tropism has been validated using a Canadian technology in clinical trials investigating the use of maraviroc in both experienced and treatment-naive patients. The present guidelines review the evidence supporting the use of genotypic assays and provide recommendations regarding tropism testing in daily clinical management.

  18. Screening of chemokine receptor CCR4 antagonists by capillary zone electrophoresis

    Directory of Open Access Journals (Sweden)

    Zhe Sun

    2011-11-01

    Full Text Available CC chemokine receptor 4 (CCR4 is a kind of G-protein-coupled receptor, which plays a pivotal role in allergic inflammation. The interaction between 2-(2-(4-chloro-phenyl-5-{[(naphthalen-1-ylmethyl-carbamoyl]-methyl}-4-oxo-thiazolidin-3-yl-N-(3-morpholin-4-yl-propyl-acetamide (S009 and the N-terminal extracellular tail (ML40 of CCR4 has been validated to be high affinity by capillary zone electrophoresis (CZE. The S009 is a known CCR4 antagonist. Now, a series of new thiourea derivatives have been synthesized. Compared with positive control S009, they were screened using ML40 as target by CZE to find some new drugs for allergic inflammation diseases. The synthesized compounds XJH-5, XJH-4, XJH-17 and XJH-1 displayed the interaction with ML40, but XJH-9, XJH-10, XJH-11, XJH-12, XJH-13, XJH-14, XJH-3, XJH-8, XJH-6, XJH-7, XJH-15, XJH-16 and XJH-2 did not bind to ML40. Both qualification and quantification characterizations of the binding were determined. The affinity of the four compounds was valued by the binding constant, which was similar with the results of chemotactic experiments. The established CEZ method is capable of sensitive and fast screening for a series of lactam analogs in the drug discovery for allergic inflammation diseases. Keywords: Capillary zone electrophoresis, CCR4 antagonist, 2-(2-(4-chloro-phenyl-5-{[(naphthalen-1-ylmethyl-carbamoyl]-methyl}-4-oxo-thiazolidin-3-yl-N-(3-morpholin-4-yl-propyl-acetamide, Interactions, Structural modification

  19. Mucosal CCR1 gene expression as a marker of molecular activity in Crohn's disease: preliminary data.

    Science.gov (United States)

    Dobre, Maria; Mănuc, Teodora Ecaterina; Milanesi, Elena; Pleşea, Iancu Emil; Ţieranu, Eugen Nicolae; Popa, Caterina; Mănuc, Mircea; Preda, Carmen Monica; Ţieranu, Ioana; Diculescu, Mihai Mircea; Ionescu, Elena Mirela; Becheanu, Gabriel

    2017-01-01

    A series of mechanisms of immune response, inflammation and apoptosis have been demonstrated to contribute to the appearance and evolution of Crohn's disease (CD) through the overexpression of several cytokines and chemokines in a susceptible host. The aim of this study was to identify the differences in gene expression profiles analyzing a panel of candidate genes in the mucosa from patients with active CD (CD-A), patients in remission (CD-R), and normal controls. Nine individuals were enrolled in the study: six CD patients (three with active lesions, three with mucosal healing) and three controls without inflammatory bowel disease (IBD) seen on endoscopy. All the individuals underwent mucosal biopsy during colonoscopy. Gene expression levels of 84 genes previously associated with CD were evaluated by polymerase chain reaction (PCR) array. Ten genes out of 84 were found significantly differentially expressed in CD-A (CCL11, CCL25, DEFA5, GCG, IL17A, LCN2, REG1A, STAT3, MUC1, CCR1) and eight genes in CD-R (CASP1, IL23A, STAT1, STAT3, TNF, CCR1, CCL5, and HSP90B1) when compared to controls. A quantitative gene expression analysis revealed that CCR1 gene was more expressed in CD-A than in CD-R. Our data suggest that CCR1 gene may be a putative marker of molecular activity of Crohn's disease. Following these preliminary data, a confirmation in larger cohort studies could represent a useful method in order to identify new therapeutic targets.

  20. Impact of MCP-1 and CCR-2 gene polymorphisms on coronary artery disease susceptibility.

    Science.gov (United States)

    Lin, Hsiu-Ling; Ueng, Kwo-Chang; Hsieh, Yih-Shou; Chiang, Whei-Ling; Yang, Shun-Fa; Chu, Shu-Chen

    2012-09-01

    Coronary artery disease (CAD) was the second leading cause of death during the last 3 years in Taiwan. Smooth muscle cells, monocytes/macrophages, and endothelial cells produce monocyte chemoattractant protein-1 (MCP-1) within atherosclerotic plaques following binding to the chemokine receptor-2 (CCR-2). Previous studies have well-documented the association between MCP-1 expression and susceptibility to, or clinicopathological features, of CAD. This study investigated the relationships between MCP-1-2518A/G and CCR-2-V64I genetic polymorphisms and CAD in the Taiwanese population. A total of 608 subjects, including 392 non-CAD controls and 216 patients with CAD, were recruited and subjected to polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) to evaluate the effects of these two polymorphic variants on CAD. Results indicated a significant association between MCP-1 -2548 gene polymorphism and susceptibility to CAD. GG genotypes (OR = 1.629; 95 % CI = 1.003-2.644), or individuals with at least one G allele (OR = 1.511; 95 % CI = 1.006-2.270), had a higher risk of CAD as compared with AA genotypes. Results also revealed that subjects with at least one A allele of the V64I CCR2 gene polymorphism had significantly increased risk of CAD. G allele in MCP-1-2518 might contribute to higher prevalence of atrial fibrillation in CAD patients (OR = 4.254; p CCR-2 64I gene polymorphisms represent important factors in determining susceptibility to CAD, and the contribution of MCP-1-2518G could be through effects on atrial fibrillation in CAD patients.

  1. CCR5 Signal Transduction in Macrophages by Human Immunodeficiency Virus and Simian Immunodeficiency Virus Envelopes

    OpenAIRE

    Arthos, James; Rubbert, Andrea; Rabin, Ronald L.; Cicala, Claudia; Machado, Elizabeth; Wildt, Kathryne; Hanbach, Meredith; Steenbeke, Tavis D.; Swofford, Ruth; Farber, Joshua M.; Fauci, Anthony S.

    2000-01-01

    The capacity of human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) envelopes to transduce signals through chemokine coreceptors on macrophages was examined by measuring the ability of recombinant envelope proteins to mobilize intracellular calcium stores. Both HIV and SIV envelopes mobilized calcium via interactions with CCR5. The kinetics of these responses were similar to those observed when macrophages were treated with MIP-1β. Distinct differences in the capacity o...

  2. $200,000 Grants Awarded to CCR Researchers for HIV/AIDS Studies | Poster

    Science.gov (United States)

    By Nancy Parrish, Staff Writer Earlier this year, the Office of AIDS Research (OAR) awarded two, two-year grants of $200,000 each to Anu Puri, Ph.D., and Robert Blumenthal, Ph.D., both of the Center for Cancer Research (CCR) Nanobiology Program, and to Eric Freed, Ph.D., of the HIV Drug Resistance Program, for their research on potential new treatments for HIV.

  3. Central vasopressin V1a receptors modulate neural processing in mothers facing intruder threat to pups

    OpenAIRE

    Caffrey, Martha K.; Nephew, Benjamin C.; Febo, Marcelo

    2009-01-01

    Vasopressin V1a receptors in the rat brain have been studied for their role in modulating aggression and anxiety. In the current study blood-oxygen-level-dependent (BOLD) functional MRI was used to test whether V1a receptors modulate neural processing in the maternal brain when dams are exposed to a male intruder. Primiparous females were given an intracerebroventricular (ICV) injection of vehicle or V1a receptor antagonist ([deamino-Pen1, O-Me-Try, Arg8]-Vasopressin, 125 ng/10 μL) 90-120 min...

  4. The Bet v 1 fold: an ancient, versatile scaffold for binding of large, hydrophobic ligands

    Directory of Open Access Journals (Sweden)

    Breiteneder Heimo

    2008-10-01

    Full Text Available Abstract Background The major birch pollen allergen, Bet v 1, is a member of the ubiquitous PR-10 family of plant pathogenesis-related proteins. In recent years, a number of diverse plant proteins with low sequence similarity to Bet v 1 was identified. In addition, determination of the Bet v 1 structure revealed the existence of a large superfamily of structurally related proteins. In this study, we aimed to identify and classify all Bet v 1-related structures from the Protein Data Bank and all Bet v 1-related sequences from the Uniprot database. Results Structural comparisons of representative members of already known protein families structurally related to Bet v 1 with all entries of the Protein Data Bank yielded 47 structures with non-identical sequences. They were classified into eleven families, five of which were newly identified and not included in the Structural Classification of Proteins database release 1.71. The taxonomic distribution of these families extracted from the Pfam protein family database showed that members of the polyketide cyclase family and the activator of Hsp90 ATPase homologue 1 family were distributed among all three superkingdoms, while members of some bacterial families were confined to a small number of species. Comparison of ligand binding activities of Bet v 1-like superfamily members revealed that their functions were related to binding and metabolism of large, hydrophobic compounds such as lipids, hormones, and antibiotics. Phylogenetic relationships within the Bet v 1 family, defined as the group of proteins with significant sequence similarity to Bet v 1, were determined by aligning 264 Bet v 1-related sequences. A distance-based phylogenetic tree yielded a classification into 11 subfamilies, nine exclusively containing plant sequences and two subfamilies of bacterial proteins. Plant sequences included the pathogenesis-related proteins 10, the major latex proteins/ripening-related proteins subfamily, and

  5. Involvement of CCR-2 chemokine receptor activation in ischemic preconditioning and postconditioning of brain in mice.

    Science.gov (United States)

    Rehni, Ashish K; Singh, Thakur Gurjeet

    2012-10-01

    The present study has been designed to investigate the potential role of CCR-2 chemokine receptor in ischemic preconditioning as well as postconditioning induced reversal of ischemia-reperfusion injury in mouse brain. Bilateral carotid artery occlusion of 17 min followed by reperfusion for 24h was employed in present study to produce ischemia and reperfusion induced cerebral injury in mice. Cerebral infarct size was measured using triphenyltetrazolium chloride staining. Memory was evaluated using elevated plus-maze test and Morris water maze test. Rota rod test was employed to assess motor incoordination. Bilateral carotid artery occlusion followed by reperfusion produced cerebral infarction and impaired memory and motor co-ordination. Three preceding episodes of bilateral carotid artery occlusion for 1 min and reperfusion of 1 min were employed to elicit ischemic preconditioning of brain, while three episodes of bilateral carotid artery occlusion for 10s and reperfusion of 10s immediately after the completion of were employed to elicit ischemic postconditioning of brain. Both prior ischemic preconditioning as well as ischemic postconditioning immediately after global cerebral ischemia prevented markedly ischemia-reperfusion-induced cerebral injury as measured in terms of infarct size, loss of memory and motor coordination. RS 102895, a selective CCR-2 chemokine receptor antagonist, attenuated the neuroprotective effect of both the ischemic preconditioning as well as postconditioning. It is concluded that the neuroprotective effect of both ischemic preconditioning as well as ischemic postconditioning may involve the activation of CCR-2 chemokine receptors. Copyright © 2012 Elsevier Ltd. All rights reserved.

  6. Current discharge management of acute coronary syndromes: data from the Rijnmond Collective Cardiology Research (CCR) study.

    Science.gov (United States)

    Yetgin, T; van der Linden, M M J M; de Vries, A G; Smits, P C; van Mechelen, R; Yap, S C; Boersma, E; Zijlstra, F; van Geuns, R-J M

    2014-01-01

    Medical discharge management of acute coronary syndromes (ACS) remains suboptimal outside randomised trials and constitutes an essential quality benchmark for ACS. We sought to evaluate the rates of key guideline-recommended pharmacological agents after ACS and characteristics associated with optimal treatment at discharge. The Rijnmond Collective Cardiology Research (CCR) registry is an ongoing prospective, observational study in the Netherlands that aims to enrol 4000 patients with ACS. We examined discharge and 1-month follow-up medication use among the first 1000 patients enrolled in the CCR registry. Logistic regression was performed to identify patient and hospital characteristics associated with collective guideline-recommended pharmacotherapy at hospital discharge. At discharge, 94 % of patients received aspirin, 100 % thienopyridines, 80 % angiotensin-converting enzyme inhibitors/angiotensin-II receptor blockers, 87 % β-blockers, 96 % statins, and 65 % the combination of all 5 agents. ST-segment elevation myocardial infarction, hypertension, hypercholesterolaemia, and enrolment in an interventional centre were positive independent predictors of 5-drug combination therapy at discharge. Negative independent predictors were unstable angina and advanced age. Current data from the CCR registry reflect a high quality of care for ACS discharge management in the Rotterdam-Rijnmond region. However, potential still remains for further optimisation.

  7. Accumulation of radioactive corrosion products on steel surfaces of VVER type nuclear reactors. I. 110mAg

    CSIR Research Space (South Africa)

    Hirschberg, G

    1999-03-01

    Full Text Available contaminants in the passive layer formed on austenitic stainless steel. In the first part of the series the accumulation of 110mAg has been investigated. Potential dependent sorption of Ag+. ions (cementation) is found to be the predominant process...

  8. 75 FR 3253 - Lamb Assembly and Test, LLC, Subsidiary of Mag Industrial Automation Systems, Machesney Park, IL...

    Science.gov (United States)

    2010-01-20

    ... DEPARTMENT OF LABOR Employment and Training Administration [TA-W-70,516] Lamb Assembly and Test, LLC, Subsidiary of Mag Industrial Automation Systems, Machesney Park, IL; Notice of Negative... workers of Lamb Technicon, a division of Unova, Warren, Michigan and Lake Orion, Michigan were previously...

  9. Visual recognition memory, manifested as long-term habituation, requires synaptic plasticity in V1.

    Science.gov (United States)

    Cooke, Sam F; Komorowski, Robert W; Kaplan, Eitan S; Gavornik, Jeffrey P; Bear, Mark F

    2015-02-01

    Familiarity with stimuli that bring neither reward nor punishment, manifested through behavioral habituation, enables organisms to detect novelty and devote cognition to important elements of the environment. Here we describe in mice a form of long-term behavioral habituation to visual grating stimuli that is selective for stimulus orientation. Orientation-selective habituation (OSH) can be observed both in exploratory behavior in an open arena and in a stereotyped motor response to visual stimuli in head-restrained mice. We found that the latter behavioral response, termed a 'vidget', requires V1. Parallel electrophysiological recordings in V1 revealed that plasticity, in the form of stimulus-selective response potentiation (SRP), occurred in layer 4 of V1 as OSH developed. Local manipulations of V1 that prevented and reversed electrophysiological modifications likewise prevented and reversed memory demonstrated behaviorally. These findings suggest that a form of long-term visual recognition memory is stored via synaptic plasticity in primary sensory cortex.

  10. Draft Genome Sequences of Vibrio alginolyticus Strains V1 and V2, Opportunistic Marine Pathogens

    DEFF Research Database (Denmark)

    Castillo, Daniel; D'Alvise, Paul; Kalatzis, Panos G.

    2015-01-01

    We announce the draft genome sequences of Vibrio alginolyticus strains V1 and V2, isolated from juvenile Sparus aurata and Dentex dentex, respectively, during outbreaks of vibriosis. The genome sequences are 5,257,950 bp with a G+C content of 44.5% for V. alginolyticus V1 and 5,068,299 bp with a G...

  11. Making the MagIC (Magnetics Information Consortium) Web Application Accessible to New Users and Useful to Experts

    Science.gov (United States)

    Minnett, R.; Koppers, A.; Jarboe, N.; Tauxe, L.; Constable, C.; Jonestrask, L.

    2017-12-01

    Challenges are faced by both new and experienced users interested in contributing their data to community repositories, in data discovery, or engaged in potentially transformative science. The Magnetics Information Consortium (https://earthref.org/MagIC) has recently simplified its data model and developed a new containerized web application to reduce the friction in contributing, exploring, and combining valuable and complex datasets for the paleo-, geo-, and rock magnetic scientific community. The new data model more closely reflects the hierarchical workflow in paleomagnetic experiments to enable adequate annotation of scientific results and ensure reproducibility. The new open-source (https://github.com/earthref/MagIC) application includes an upload tool that is integrated with the data model to provide early data validation feedback and ease the friction of contributing and updating datasets. The search interface provides a powerful full text search of contributions indexed by ElasticSearch and a wide array of filters, including specific geographic and geological timescale filtering, to support both novice users exploring the database and experts interested in compiling new datasets with specific criteria across thousands of studies and millions of measurements. The datasets are not large, but they are complex, with many results from evolving experimental and analytical approaches. These data are also extremely valuable due to the cost in collecting or creating physical samples and the, often, destructive nature of the experiments. MagIC is heavily invested in encouraging young scientists as well as established labs to cultivate workflows that facilitate contributing their data in a consistent format. This eLightning presentation includes a live demonstration of the MagIC web application, developed as a configurable container hosting an isomorphic Meteor JavaScript application, MongoDB database, and ElasticSearch search engine. Visitors can explore the Mag

  12. [Comparison of manual and automated (MagNA Pure) nucleic acid isolation methods in molecular diagnosis of HIV infections].

    Science.gov (United States)

    Alp, Alpaslan; Us, Dürdal; Hasçelik, Gülşen

    2004-01-01

    Rapid quantitative molecular methods are very important for the diagnosis of human immunodeficiency virus (HIV) infections, assessment of prognosis and follow up. The purpose of this study was to compare and evaluate the performances of conventional manual extraction method and automated MagNA Pure system, for the nucleic acid isolation step which is the first and most important step in molecular diagnosis of HIV infections. Plasma samples of 35 patients in which anti-HIV antibodies were found as positive by microparticule enzyme immunoassay and confirmed by immunoblotting method, were included in the study. The nucleic acids obtained simultaneously by manual isolation kit (Cobas Amplicor, HIV-1 Monitor Test, version 1.5, Roche Diagnostics) and automated system (MagNA Pure LC Total Nucleic Acid Isolation Kit, Roche Diagnostics), were amplified and detected in Cobas Amplicor (Roche Diagnostics) instrument. Twenty three of 35 samples (65.7%) were found to be positive, and 9 (25.7%) were negative by both of the methods. The agreement between the methods were detected as 91.4%, for qualitative results. Viral RNA copies detected by manual and MagNA Pure isolation methods were found between 76.0-7.590.000 (mean: 487.143) and 113.0-20.300.0000 (mean: 2.174.097) copies/ml, respectively. When both of the overall and individual results were evaluated, the number of RNA copies obtained with automatized system, were found higher than the manual method (p<0.05). Three samples which had low numbers of nucleic acids (113, 773, 857, respectively) with MagNA Pure, yielded negative results with manual method. In conclusion, the automatized MagNA Pure system was found to be a reliable, rapid and practical method for the isolation of HIV-RNA.

  13. Frequencies of CCR5-D32, CCR2-64I and SDF1-3’A mutations in Human Immunodeficiency Virus (HIV seropositive subjects and seronegative individuals from the state of Pará in Brazilian Amazonia

    Directory of Open Access Journals (Sweden)

    Fernanda Andreza de Pinho Lott Carvalhaes

    2005-12-01

    Full Text Available The distribution of genetic polymorphisms of chemokine receptors CCR5-delta32, CCR2-64I and chemokine (SDF1-3’A mutations were studied in 110 Human Immunodeficiency Virus type 1 (HIV-1 seropositive individuals (seropositive group and 139 seronegative individuals (seronegative group from the population of the northern Brazilian city of Belém which is the capital of the state of Pará in the Brazilian Amazon. The CCR5-delta32 mutation was found in the two groups at similar frequencies, i.e. 2.2% for the seronegative group and 2.7% for the seropositive group. The frequencies of the SDF1-3’A mutation were 21.0% for the seronegative group and 15.4% for the seropositive group, and the CCR2-64I allele was found at frequencies of 12.5% for the seronegative group and 5.4% for the seropositive group. Genotype distributions were consistent with Hardy-Weinberg expectations in both groups, suggesting that none of the three mutations has a detectable selective effect. Difference in the allelic and genotypic frequencies was statistically significant for the CCR2 locus, the frequency in the seronegative group being twice that found in the seropositive group. This finding may indicate a protective effect of the CCR2-64I mutation in relation to HIV transmission. However, considering that the CCR2-64I mutation has been more strongly associated with a decreased risk for progression for AIDS than to the resistance to the HIV infection, this could reflect an aspect of population structure or a Type I error.

  14. Characterization of V1R receptor (ora) genes in Lake Victoria cichlids.

    Science.gov (United States)

    Ota, Tomoki; Nikaido, Masato; Suzuki, Hikoyu; Hagino-Yamagishi, Kimiko; Okada, Norihiro

    2012-05-15

    Although olfaction could play a crucial role in underwater habitats by allowing fish to sense a variety of nonvolatile chemical signals, the importance of olfaction in species-rich cichlids is still controversial. In particular, examining whether cichlids rely on olfaction for reproduction is of primary interest to understand the mechanisms of speciation. In the present study, we explored the V1R (also known as ora) genes, which are believed to encode reproductive pheromone receptors in fish, in the genomes of Lake Victoria cichlids. By screening a bacterial artificial chromosome library, we identified all six intact V1R genes (V1R1 to V1R6) that have been reported in other teleost fish. Furthermore, RT-PCR and in situ hybridization analyses showed that all of the V1R genes were expressed in the olfactory epithelium, indicating that these receptors are functional in cichlids. These observations indicate that cichlids use V1R-mediated olfaction in some ways for their social behaviors. Copyright © 2012 Elsevier B.V. All rights reserved.

  15. Mixing of Chromatic and Luminance Retinal Signals in Primate Area V1.

    Science.gov (United States)

    Li, Xiaobing; Chen, Yao; Lashgari, Reza; Bereshpolova, Yulia; Swadlow, Harvey A; Lee, Barry B; Alonso, Jose Manuel

    2015-07-01

    Vision emerges from activation of chromatic and achromatic retinal channels whose interaction in visual cortex is still poorly understood. To investigate this interaction, we recorded neuronal activity from retinal ganglion cells and V1 cortical cells in macaques and measured their visual responses to grating stimuli that had either luminance contrast (luminance grating), chromatic contrast (chromatic grating), or a combination of the two (compound grating). As with parvocellular or koniocellular retinal ganglion cells, some V1 cells responded mostly to the chromatic contrast of the compound grating. As with magnocellular retinal ganglion cells, other V1 cells responded mostly to the luminance contrast and generated a frequency-doubled response to equiluminant chromatic gratings. Unlike magnocellular and parvocellular retinal ganglion cells, V1 cells formed a unimodal distribution for luminance/color preference with a 2- to 4-fold bias toward luminance. V1 cells associated with positive local field potentials in deep layers showed the strongest combined responses to color and luminance and, as a population, V1 cells encoded a diverse combination of luminance/color edges that matched edge distributions of natural scenes. Taken together, these results suggest that the primary visual cortex combines magnocellular and parvocellular retinal inputs to increase cortical receptive field diversity and to optimize visual processing of our natural environment. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  16. Single-molecule analysis of inhibitory pausing states of V1-ATPase.

    Science.gov (United States)

    Uner, Naciye Esma; Nishikawa, Yoshihiro; Okuno, Daichi; Nakano, Masahiro; Yokoyama, Ken; Noji, Hiroyuki

    2012-08-17

    V(1)-ATPase, the hydrophilic V-ATPase domain, is a rotary motor fueled by ATP hydrolysis. Here, we found that Thermus thermophilus V(1)-ATPase shows two types of inhibitory pauses interrupting continuous rotation: a short pause (SP, 4.2 s) that occurred frequently during rotation, and a long inhibitory pause (LP, >30 min) that terminated all active rotations. Both pauses occurred at the same angle for ATP binding and hydrolysis. Kinetic analysis revealed that the time constants of inactivation into and activation from the SP were too short to represent biochemically predicted ADP inhibition, suggesting that SP is a newly identified inhibitory state of V(1)-ATPase. The time constant of inactivation into LP was 17 min, consistent with one of the two time constants governing the inactivation process observed in bulk ATPase assay. When forcibly rotated in the forward direction, V(1) in LP resumed active rotation. Solution ADP suppressed the probability of mechanical activation, suggesting that mechanical rotation enhanced inhibitory ADP release. These features were highly consistent with mechanical activation of ADP-inhibited F(1), suggesting that LP represents the ADP-inhibited state of V(1)-ATPase. Mechanical activation largely depended on the direction and angular displacement of forced rotation, implying that V(1)-ATPase rotation modulates the off rate of ADP.

  17. METEOR v1.0 - Design and structure of the software package; METEOR v1.0 - Estructura y modulos informaticos

    Energy Technology Data Exchange (ETDEWEB)

    Palomo, E.

    1994-07-01

    This script describes the structure and the separated modules of the software package METEOR for the statistical analysis of meteorological data series. It contains a systematic description of the subroutines of METEOR and, also, of the required shape for input and output files. The original version of METEOR have been developed by Ph.D. Elena Palomo, CIEMAT-IER, GIMASE. It is built by linking programs and routines written in FORTRAN 77 and it adds thc graphical capabilities of GNUPLOT. The shape of this toolbox was designed following the criteria of modularity, flexibility and agility criteria. All the input, output and analysis options are structured in three main menus: i) the first is aimed to evaluate the quality of the data set; ii) the second is aimed for pre-processing of the data; and iii) the third is aimed towards the statistical analyses and for creating the graphical outputs. Actually the information about METEOR is constituted by three documents written in spanish: 1) METEOR v1.0: User's guide; 2) METEOR v1.0: A usage example; 3) METEOR v 1.0: Design and structure of the software package. (Author)

  18. Regulation of Blood Pressure by Targeting CaV1.2-Galectin-1 Protein Interaction.

    Science.gov (United States)

    Hu, Zhenyu; Li, Guang; Wang, Jiong-Wei; Chong, Suet Yen; Yu, Dejie; Wang, Xiaoyuan; Soon, Jia Lin; Liang, Mui Cheng; Wong, Yuk Peng; Huang, Na; Colecraft, Henry M; Liao, Ping; Soong, Tuck Wah

    2018-04-12

    Background -L-type Ca V 1.2 channels play crucial roles in regulation of blood pressure. Galectin-1 (Gal-1), has been reported to bind to the I-II loop of Ca V 1.2 channels to reduce their current density. However, the mechanistic understanding for the down-regulation of Ca V 1.2 channels by Gal-1, and whether Gal-1 plays a direct role in blood pressure regulation remain unclear. Methods - In vitro experiments involving co-IP, western blot, patch-clamp recordings, immunohistochemistry and pressure myography were used to evaluate the molecular mechanisms by which Gal-1 down-regulates Ca V 1.2 channel in transfected HEK 293 cells, smooth muscle cells, arteries from Lgasl1 -/- mice, rat and human patients. In vivo experiments involving delivery of Tat-e9c peptide and AAV5-Gal-1 into rats were performed to investigate the effect of targeting Ca V 1.2-Gal-1 interaction on blood pressure monitored by tail cuff or telemetry methods. Results -Our study reveals that Gal-1 is a key regulator for proteasomal degradation of Ca V 1.2 channels. Gal-1 competed allosterically with Ca V β subunit for binding to the I-II loop of Ca V 1.2 channel. This competitive disruption of Ca V β binding led to Ca V 1.2 degradation by exposing the channels to poly-ubiquitination. Notably, we demonstrated that the inverse relationship of reduced Gal-1 and increased Ca V 1.2 protein levels in arteries was associated with hypertension in hypertensive rats and patients, and Gal-1 deficiency induces higher blood pressure in mice due to up-regulated Ca V 1.2 protein level in arteries. To directly regulate blood pressure by targeting the Ca V 1.2-Gal-1 interaction, we administered Tat-e9c, a peptide that competed for binding of Gal-1, by a mini-osmotic pump and this specific disruption of Ca V 1.2-Gal-1 coupling increased smooth muscle Ca V 1.2 currents, induced larger arterial contraction and caused hypertension in rats. In contrasting experiments, over-expression of Gal-1 in smooth muscle by a

  19. Evaluation of the effect of the specific CCR1 antagonist CP-481715 on the clinical and cellular responses observed following epicutaneous nickel challenge in human subjects

    DEFF Research Database (Denmark)

    Borregaard, Jeanett; Skov, Lone; Wang, Lisy

    2008-01-01

    BACKGROUND: The CC-chemokine receptor-1 (CCR1) is thought to be involved in recruitment of inflammatory cells in allergic contact dermatitis (ACD). CP-481715 is a specific antagonist of CCR1. OBJECTIVES: To determine the inhibitory effects of CP-418 715 in ACD by evaluating the clinical signs....... CONCLUSIONS: Blocking of CCR1 only partly inhibited clinical manifestations of ACD. Several chemokine receptors are likely relevant for the cellular influx observed in ACD lesions....

  20. Components of the CCR4-NOT complex function as nuclear hormone receptor coactivators via association with the NRC-interacting Factor NIF-1.

    Science.gov (United States)

    Garapaty, Shivani; Mahajan, Muktar A; Samuels, Herbert H

    2008-03-14

    CCR4-NOT is an evolutionarily conserved, multicomponent complex known to be involved in transcription as well as mRNA degradation. Various subunits (e.g. CNOT1 and CNOT7/CAF1) have been reported to be involved in influencing nuclear hormone receptor activities. Here, we show that CCR4/CNOT6 and RCD1/CNOT9, members of the CCR4-NOT complex, potentiate nuclear receptor activity. RCD1 interacts in vivo and in vitro with NIF-1 (NRC-interacting factor), a previously characterized nuclear receptor cotransducer that activates nuclear receptors via its interaction with NRC. As with NIF-1, RCD1 and CCR4 do not directly associate with nuclear receptors; however, they enhance ligand-dependent transcriptional activation by nuclear hormone receptors. CCR4 mediates its effect through the ligand binding domain of nuclear receptors and small interference RNA-mediated silencing of endogenous CCR4 results in a marked decrease in nuclear receptor activation. Furthermore, knockdown of CCR4 results in an attenuated stimulation of RARalpha target genes (e.g. Sox9 and HoxA1) as shown by quantitative PCR assays. The silencing of endogenous NIF-1 also resulted in a comparable decrease in the RAR-mediated induction of both Sox9 and HoxA1. Furthermore, CCR4 associates in vivo with NIF-1. In addition, the CCR4-enhanced transcriptional activation by nuclear receptors is dependent on NIF-1. The small interference RNA-mediated knockdown of NIF-1 blocks the ligand-dependent potentiating effect of CCR4. Our results suggest that CCR4 plays a role in the regulation of certain endogenous RARalpha target genes and that RCD1 and CCR4 might mediate their function through their interaction with NIF-1.

  1. Similarity transformed coupled cluster response (ST-CCR) theory--a time-dependent similarity transformed equation-of-motion coupled cluster (STEOM-CC) approach.

    Science.gov (United States)

    Landau, Arie

    2013-07-07

    This paper presents a new method for calculating spectroscopic properties in the framework of response theory utilizing a sequence of similarity transformations (STs). The STs are preformed using the coupled cluster (CC) and Fock-space coupled cluster operators. The linear and quadratic response functions of the new similarity transformed CC response (ST-CCR) method are derived. The poles of the linear response yield excitation-energy (EE) expressions identical to the ones in the similarity transformed equation-of-motion coupled cluster (STEOM-CC) approach. ST-CCR and STEOM-CC complement each other, in analogy to the complementarity of CC response (CCR) and equation-of-motion coupled cluster (EOM-CC). ST-CCR/STEOM-CC and CCR/EOM-CC yield size-extensive and size-intensive EEs, respectively. Other electronic-properties, e.g., transition dipole strengths, are also size-extensive within ST-CCR, in contrast to STEOM-CC. Moreover, analysis suggests that in comparison with CCR, the ST-CCR expressions may be confined to a smaller subspace, however, the precise scope of the truncation can only be determined numerically. In addition, reformulation of the time-independent STEOM-CC using the same parameterization as in ST-CCR, as well as an efficient truncation scheme, is presented. The shown convergence of the time-dependent and time-independent expressions displays the completeness of the presented formalism.

  2. Upregulation of the Chemokine Receptor CCR2B in Epstein‒Barr Virus-Positive Burkitt Lymphoma Cell Lines with the Latency III Program

    Directory of Open Access Journals (Sweden)

    Svetlana Kozireva

    2018-05-01

    Full Text Available CCR2 is the cognate receptor to the chemokine CCL2. CCR2–CCL2 signaling mediates cancer progression and metastasis dissemination. However, the role of CCR2–CCL2 signaling in pathogenesis of B-cell malignancies is not clear. Previously, we showed that CCR2B was upregulated in ex vivo peripheral blood B cells upon Epstein‒Barr virus (EBV infection and in established lymphoblastoid cell lines with the EBV latency III program. EBV latency III is associated with B-cell lymphomas in immunosuppressed patients. The majority of EBV-positive Burkitt lymphoma (BL tumors are characterized by latency I, but the BL cell lines drift towards latency III during in vitro culture. In this study, the CCR2A and CCR2B expression was assessed in the isogenic EBV-positive BL cell lines with latency I and III using RT-PCR, immunoblotting, and immunostaining analyses. We found that CCR2B is upregulated in the EBV-positive BL cells with latency III. Consequently, we detected the migration of latency III cells toward CCL2. Notably, the G190A mutation, corresponding to SNP CCR2-V64I, was found in one latency III cell line with a reduced migratory response to CCL2. The upregulation of CCR2B may contribute to the enhanced migration of malignant B cells into CCL2-rich compartments.

  3. Uploading, Searching and Visualizing of Paleomagnetic and Rock Magnetic Data in the Online MagIC Database

    Science.gov (United States)

    Minnett, R.; Koppers, A.; Tauxe, L.; Constable, C.; Donadini, F.

    2007-12-01

    The Magnetics Information Consortium (MagIC) is commissioned to implement and maintain an online portal to a relational database populated by both rock and paleomagnetic data. The goal of MagIC is to archive all available measurements and derived properties from paleomagnetic studies of directions and intensities, and for rock magnetic experiments (hysteresis, remanence, susceptibility, anisotropy). MagIC is hosted under EarthRef.org at http://earthref.org/MAGIC/ and will soon implement two search nodes, one for paleomagnetism and one for rock magnetism. Currently the PMAG node is operational. Both nodes provide query building based on location, reference, methods applied, material type and geological age, as well as a visual map interface to browse and select locations. Users can also browse the database by data type or by data compilation to view all contributions associated with well known earlier collections like PINT, GMPDB or PSVRL. The query result set is displayed in a digestible tabular format allowing the user to descend from locations to sites, samples, specimens and measurements. At each stage, the result set can be saved and, where appropriate, can be visualized by plotting global location maps, equal area, XY, age, and depth plots, or typical Zijderveld, hysteresis, magnetization and remanence diagrams. User contributions to the MagIC database are critical to achieving a useful research tool. We have developed a standard data and metadata template (version 2.3) that can be used to format and upload all data at the time of publication in Earth Science journals. Software tools are provided to facilitate population of these templates within Microsoft Excel. These tools allow for the import/export of text files and provide advanced functionality to manage and edit the data, and to perform various internal checks to maintain data integrity and prepare for uploading. The MagIC Contribution Wizard at http://earthref.org/MAGIC/upload.htm executes the upload

  4. Information about environmental effects of Bohunice NPPs V-1 and V-2 within February 2002

    International Nuclear Information System (INIS)

    2002-01-01

    In this leaflet the results of monitoring of chemical gaseous and liquid effluents into the rivers Vah and Dudvah as well as of radiation monitoring of Bohunice V-1 and V-2 NPPs are presented. The radioactive effluents within a February 2002 (for NPP V-1 and NPP V-2, respectively) were: 0.571 TBq and 0.664 TBq of rare gases, 0.711 MBq and 0.244 MBq of aero-soles, 2.121 MBq and 0.138 MBq of iodine, 2.022 MBq and 0.564 MBq of corrosive and fission products, and 1.420 TBq and 1.643 TBq of tritium. For the period January - February 2002 these radioactive effluents represent for rare gases 1.286 TBq for NPP V-1 and 1.475 TBq for NPP V-2 (2.761 TBq (0.069% of annually limit (AL) for the locality Bohunice), for aerosols 2.645 MBq for NPP V-1 and 0.542 MBq for NPP V-2 (3.187 MBq (0.002% of AL for the locality Bohunice), for corrosive and fission products 3.848 MBq for NPP V-1 and 1.510 MBq for NPP V-2 (5.358 MBq (0.01% of AL) for the locality Bohunice), and for iodine 2.616 MBq for NPP V-1 and 0.279 MBq (2.894 MBq (0.002% of AL) for the locality Bohunice), and for tritium it is 2.395 TBq for NPP V-1 and 3.532 TBq for NPP V-2 (5.358 TBq (13.56% of AL) for the locality Bohunice

  5. Kinetics of manganese in MAG/MIG welding with a 18/8/6 wire

    International Nuclear Information System (INIS)

    Tusek, J.

    2001-01-01

    The paper deals with a study of MAG/MIG welding of low-alloy ferritic steel and high-alloy austenitic steel with a 18/8/6 wire. Manganese burn-off from the wire in welding a single-V butt weld was studied. It was found that manganese burns off in the arc during melting of a droplet at the wire end, and from the weld pool during weld formation. The range of manganese burn-of-depends mainly on the type of shielding gas used and the arc length,i. e., from the arc voltage. The manganese burn-off increases with an increase of the content of active gases, i.e., CO 2 and O 2 in the neutral gas i. e., argon. It also increases with an increase in arc voltage. The longer the welding arc, the longer exposition of the filler materials to the welding arc and the wider the penetration, Which allows manganese vapours to evaporate from the weld pool. The most important finding is that manganese burn-off from the 18/8/6 wire during welding of austenitic stainless steel with low-alloy ferritic steel is considerably strong, i.e., from 20% to 30%; nevertheless the wire concerned is perfectly suitable for welding of different types of steel. (Author) 23 refs

  6. magHD: a new approach to multi-dimensional data storage, analysis, display and exploitation

    International Nuclear Information System (INIS)

    Angleraud, Christophe

    2014-01-01

    The ever increasing amount of data and processing capabilities – following the well- known Moore's law – is challenging the way scientists and engineers are currently exploiting large datasets. The scientific visualization tools, although quite powerful, are often too generic and provide abstract views of phenomena, thus preventing cross disciplines fertilization. On the other end, Geographic information Systems allow nice and visually appealing maps to be built but they often get very confused as more layers are added. Moreover, the introduction of time as a fourth analysis dimension to allow analysis of time dependent phenomena such as meteorological or climate models, is encouraging real-time data exploration techniques that allow spatial-temporal points of interests to be detected by integration of moving images by the human brain. Magellium is involved in high performance image processing chains for satellite image processing as well as scientific signal analysis and geographic information management since its creation (2003). We believe that recent work on big data, GPU and peer-to-peer collaborative processing can open a new breakthrough in data analysis and display that will serve many new applications in collaborative scientific computing, environment mapping and understanding. The magHD (for Magellium Hyper-Dimension) project aims at developing software solutions that will bring highly interactive tools for complex datasets analysis and exploration commodity hardware, targeting small to medium scale clusters with expansion capabilities to large cloud based clusters

  7. Diagnosing the Stagnation Conditions of MagLIF Implosions Using Co and Kr dopants

    Science.gov (United States)

    Harding, E. C.; Hansen, S. B.; Harvey-Thompson, A. J.; Weis, M. R.; Hahn, K. D.; Gomez, M. R.; Knapp, P. F.; Slutz, S. A.; Geissel, M.; Ampleford, D. J.; Jennings, C. A.; Peterson, K.; Rochau, G. A.; Doron, R.; Stambulchik, E.; Nedostup, O.; Maron, Y.; Golovkin, I.

    2017-10-01

    Recent experiments on the Z-machine tested several new diagnostic techniques for investigating the stagnation conditions and the origins of the mix present in a Magnetized Liner Inertial Fusion (MagLIF) target. For the first time we have collected K-shell spectra from a low-concentration, Kr dopant placed in the gaseous D2 fuel. In addition, thin Co coatings were strategically applied to three different internal surfaces of the target in order to assess which surfaces actively contribute to the contamination of the fuel. Both imaging spectroscopy and narrow-band crystal imaging were used to identify the location of He-like Co ions. The Te and ne of the Co is inferred by fitting the He-alpha lines and the near-by Li-like satellites. The experimental measurements and the challenges associated with the analysis will be discussed. Sandia Natl Lab is a multi-mission laboratory managed and operated by National Technology and Engineering Solutions of Sandia, LLC., a wholly owned subsidiary of Honeywell International, Inc., for the U.S. DOE NNSA under contract DE-NA-0003525.

  8. Case study : MAG Geislingen : a public park atop a shopping mall in Germany

    Energy Technology Data Exchange (ETDEWEB)

    Eckert, H. [ZinCo GmbH, Unterensingen (Germany)

    2004-07-01

    A design retrofit competition for the Maschinenfabrik Geislingen (MAG) in the town of Geislingen, Germany, was won by the architectural firm Haring und Zoller from Stuttgart. The town of Geislingen dates back more than 1000 years. As such, new projects must ensure an aesthetic compatibility between the past and the present. The resulting design, with green roof, incorporated a shopping area, a sports and leisure complex and an underground parking lot in a sloped terrain. The extensive green roofs, which total 100,000 square feet on this private property in the town centre, are maintained in the long term by the town gardeners. The cooperation between the client Kaufland Stiftung Co., the architectural firm and the local planning authorities was central to the projects success. Together they managed to achieve this unique project which attracts visitors from three continents and has resulted in a several imitations. The extensive part of the green roof, which is carried out as sedum green roofs, is not open to the public and must be maintained once a year. A drainage layer made of Floradrain{sup R} elements is installed underneath the entire green roof system independently from the extensive or intensive build-up type of green roof. All surfaces, boundaries and foundations could be built directly into the drainage layer without impeding the draining rain water. 9 figs.

  9. Migration to Current Open Source Technologies by MagIC Enables a More Responsive Website, Quicker Development Times, and Increased Community Engagement

    Science.gov (United States)

    Jarboe, N.; Minnett, R.; Koppers, A.; Constable, C.; Tauxe, L.; Jonestrask, L.

    2017-12-01

    The Magnetics Information Consortium (MagIC) supports an online database for the paleo, geo, and rock magnetic communities ( https://earthref.org/MagIC ). Researchers can upload data into the archive and download data as selected with a sophisticated search system. MagIC has completed the transition from an Oracle backed, Perl based, server oriented website to an ElasticSearch backed, Meteor based thick client website technology stack. Using JavaScript on both the sever and the client enables increased code reuse and allows easy offloading many computational operations to the client for faster response. On-the-fly data validation, column header suggestion, and spreadsheet online editing are some new features available with the new system. The 3.0 data model, method codes, and vocabulary lists can be browsed via the MagIC website and more easily updated. Source code for MagIC is publicly available on GitHub ( https://github.com/earthref/MagIC ). The MagIC file format is natively compatible with the PmagPy ( https://github.com/PmagPy/PmagPy) paleomagnetic analysis software. MagIC files can now be downloaded from the database and viewed and interpreted in the PmagPy GUI based tool, pmag_gui. Changes or interpretations of the data can then be saved by pmag_gui in the MagIC 3.0 data format and easily uploaded to the MagIC database. The rate of new contributions to the database has been increasing with many labs contributing measurement level data for the first time in the last year. Over a dozen file format conversion scripts are available for translating non-MagIC measurement data files into the MagIC format for easy uploading. We will continue to work with more labs until the whole community has a manageable workflow for contributing their measurement level data. MagIC will continue to provide a global repository for archiving and retrieving paleomagnetic and rock magnetic data and, with the new system in place, be able to more quickly respond to the community

  10. 99mTc-MAG3 as a single modality investigative agent for evaluation of renal diseases in children

    International Nuclear Information System (INIS)

    Bal, C.S.; Padhy, A.K.; Handa, R.; Bajpai, M.

    1998-01-01

    Optimal assessment of a child with congenital or acquired renal disease consists of quantitation of renal cortical and excretory function. This at present is routinely done with a 99m Tc-GHA/DMSA and 99m Tc-DTPA scans, respectively. This study was undertaken to assess if 99m Tc-MAG 3 can be utilized as a single modality investigation to provide adequate information about these functions. Sixteen children attending the pediatric urology clinic at All India Institute of Medical Sciences (AIIMS), New Delhi with a variety of renal disorders like posterior urethral valves, hydronephrosis vesicoureteral reflux etc. were included in the study. All the cases were subjected to 99m Tc-MAG 3 , 99m -DTPA and 99m Tc-GHA scans on separate occasions, but as close to one other as possible. The time required for the completion of a 99m Tc-MAG 3 renogram was only twenty minutes. 99m Tc-MAG 3 produced significantly better scintigraphic images of the kidneys and ureters, enabling differentiation between pelviureteric and vesicoureteric junction obstruction. Because of the abundance of photons in 99m Tc-MAG 3 , antegrade ureteric visualization was possible in nine renal units with active ureteric peristalsis appreciable in three renal units. Being a renal tubular agent, it gave a better assessment of renal health of the involved renal unit as compared to 99m Tc-DTPA, a glomerular filtration agent. Detection of renal scars as compared to 99m Tc-GHA showed a sensitivity of 69% and specificity of 93%. Amount of radioactivity required was consistently less than either GHA or DTPA scans. Use of 99m Tc-MAG 3 for renal functional evaluation may result in decreased radiation exposure and optional gamma camera utilization. Besides it is more cost-effective and may reduce the number of investigations that a child needs to be subjected to. It may be of immense value in a country like India where patients have to travel long distances to avail such investigations in a few, overworked nuclear

  11. A Chimeric NaV1.8 Channel Expression System Based on HEK293T Cell Line

    Directory of Open Access Journals (Sweden)

    Xi Zhou

    2018-04-01

    Full Text Available Among the nine voltage-gated sodium channel (NaV subtypes, NaV1.8 is an attractive therapeutic target for pain. The heterologous expression of recombinant NaV1.8 currents is of particular importance for its electrophysiological and pharmacological studies. However, NaV1.8 expresses no or low-level functional currents when transiently transfected into non-neuronal cell lines. The present study aims to explore the molecular determinants limiting its functional expression and accordingly establish a functional NaV1.8 expression system. We conducted screening analysis of the NaV1.8 intracellular loops by constructing NaV chimeric channels and confirmed that the NaV1.8 C-terminus was the only limiting factor. Replacing this sequence with that of NaV1.4, NaV1.5, or NaV1.7 constructed functional channels (NaV1.8/1.4L5, NaV1.8/1.5L5, and NaV1.8/1.7L5, respectively, which expressed high-level NaV1.8-like currents in HEK293T cells. The chimeric channel NaV1.8/1.7L5 displayed much faster inactivation of its macroscopic currents than NaV1.8/1.4L5 and NaV1.8/1.5L5, and it was the most similar to wild-type NaV1.8 expressed in ND7/23 cells. Its currents were very stable during repetitive depolarizations, while its repriming kinetic was different from wild-type NaV1.8. Most importantly, NaV1.8/1.7L5 pharmacologically resembled wild-type NaV1.8 as revealed by testing their susceptibility to two NaV1.8 selective antagonists, APETx-2 and MrVIB. NaV chimeras study showed that at least the domain 2 and domain 4 of NaV1.8 were involved in binding with APETx-2. Our study provided new insights into the function of NaV1.8 intracellular loops, as well as a reliable and convenient expression system which could be useful in NaV1.8 studies.

  12. Chemokine CCL2 and its receptor CCR2 in the medullary dorsal horn are involved in trigeminal neuropathic pain

    Directory of Open Access Journals (Sweden)

    Zhang Zhi-Jun

    2012-07-01

    Full Text Available Abstract Background Neuropathic pain in the trigeminal system is frequently observed in clinic, but the mechanisms involved are largely unknown. In addition, the function of immune cells and related chemicals in the mechanism of pain has been recognized, whereas few studies have addressed the potential role of chemokines in the trigeminal system in chronic pain. The present study was undertaken to test the hypothesis that chemokine C-C motif ligand 2 (CCL2-chemokine C-C motif receptor 2 (CCR2 signaling in the trigeminal nucleus is involved in the maintenance of trigeminal neuropathic pain. Methods The inferior alveolar nerve and mental nerve transection (IAMNT was used to induce trigeminal neuropathic pain. The expression of ATF3, CCL2, glial fibrillary acidic protein (GFAP, and CCR2 were detected by immunofluorescence histochemical staining and western blot. The cellular localization of CCL2 and CCR2 were examined by immunofluorescence double staining. The effect of a selective CCR2 antagonist, RS504393 on pain hypersensitivity was checked by behavioral testing. Results IAMNT induced persistent (>21 days heat hyperalgesia of the orofacial region and ATF3 expression in the mandibular division of the trigeminal ganglion. Meanwhile, CCL2 expression was increased in the medullary dorsal horn (MDH from 3 days to 21 days after IAMNT. The induced CCL2 was colocalized with astroglial marker GFAP, but not with neuronal marker NeuN or microglial marker OX-42. Astrocytes activation was also found in the MDH and it started at 3 days, peaked at 10 days and maintained at 21 days after IAMNT. In addition, CCR2 was upregulated by IAMNT in the ipsilateral medulla and lasted for more than 21 days. CCR2 was mainly colocalized with NeuN and few cells were colocalized with GFAP. Finally, intracisternal injection of CCR2 antagonist, RS504393 (1, 10 μg significantly attenuated IAMNT-induced heat hyperalgesia. Conclusion The data suggest that CCL2-CCR

  13. Downregulation of mouse CCR3 by lentiviral shRNA inhibits proliferation and induces apoptosis of mouse eosinophils.

    Science.gov (United States)

    Zhu, Xin-Hua; Liao, Bing; Xu, Yi; Liu, Ke; Huang, Yun; Huang, Quan-Long; Liu, Yue-Hui

    2017-02-01

    RNA interference has been considered as an effective gene silencing method in basic and preclinical investigations. The aims of the present study were to construct a lentiviral vector expressing a short hairpin RNA (shRNA) targeting the murine CC chemokine receptor 3 (mCCR3), and to investigate its effects on the proliferation and apoptosis of mouse eosinophils. A recombinant lentiviral vector expressing four fragments of mouse CCR3 shRNA (pLVX‑mCCR3‑1+2+3+4‑shRNA) was constructed using subcloning techniques. This novel lentivirus was then packaged into 293T cells by co‑transduction with plasmids, including Baculo p35, pCMV R8.2 and VSV. The interference effects of the vector were verified using polymerase chain reaction (PCR) and western blot analyses. The effects of the interference on the proliferation and apoptosis of mouse eosinophils were investigated using 3‑(4,5‑dimethylthiazol‑2‑yl)‑5‑(3‑carboxymethoxyphenyl)‑2‑(4‑sulfophenyl)‑2H‑tetrazolium and terminal deoxynucleotidyl transferase dUTP nick end labeling methods, respectively. The results of the PCR and western blot analyses confirmed that the novel recombinant vector, pLVX‑mCCR3‑1+2+3+4‑shRNA, had high efficiency in inhibiting the mRNA and protein expression levels of mCCR3 in mouse eosinophils. The downregulation of mCCR3 significantly inhibited proliferation of the eosinophils. Furthermore, the present study found that the downregulation of mCCR3 significantly promoted apoptosis of the eosinophils. Therefore, the downregulation of mCCR3 led to the inhibition of proliferation and induction of apoptosis in mouse eosinophils. The predominant characteristics of allergic rhinitis are eosinophil infiltration and release of inflammatory mediators, which appear in a variety of clinical manifestations. The results of the present study indicate that mCCR3 silencing may serve as a putative approach for the treatment of allergic rhinitis.

  14. Protection against bronchiolitis obliterans syndrome is associated with allograft CCR7+ CD45RA- T regulatory cells.

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    Aric L Gregson

    2010-06-01

    Full Text Available Bronchiolitis obliterans syndrome (BOS is the major obstacle to long-term survival after lung transplantation, yet markers for early detection and intervention are currently lacking. Given the role of regulatory T cells (Treg in modulation of immunity, we hypothesized that frequencies of Treg in bronchoalveolar lavage fluid (BALF after lung transplantation would predict subsequent development of BOS. Seventy BALF specimens obtained from 47 lung transplant recipients were analyzed for Treg lymphocyte subsets by flow cytometry, in parallel with ELISA measurements of chemokines. Allograft biopsy tissue was stained for chemokines of interest. Treg were essentially all CD45RA(-, and total Treg frequency did not correlate to BOS outcome. The majority of Treg were CCR4(+ and CD103(- and neither of these subsets correlated to risk for BOS. In contrast, higher percentages of CCR7(+ Treg correlated to reduced risk of BOS. Additionally, the CCR7 ligand CCL21 correlated with CCR7(+ Treg frequency and inversely with BOS. Higher frequencies of CCR7(+ CD3(+CD4(+CD25(hiFoxp3(+CD45RA(- lymphocytes in lung allografts is associated with protection against subsequent development of BOS, suggesting that this subset of putative Treg may down-modulate alloimmunity. CCL21 may be pivotal for the recruitment of this distinct subset to the lung allograft and thereby decrease the risk for chronic rejection.

  15. Influence of the CCR-5/MIP-1 α axis in the pathogenesis of Rocio virus encephalitis in a mouse model.

    Science.gov (United States)

    Chávez, Juliana H; França, Rafael F O; Oliveira, Carlo J F; de Aquino, Maria T P; Farias, Kleber J S; Machado, Paula R L; de Oliveira, Thelma F M; Yokosawa, Jonny; Soares, Edson G; da Silva, João S; da Fonseca, Benedito A L; Figueiredo, Luiz T M

    2013-11-01

    Rocio virus (ROCV) caused an outbreak of human encephalitis during the 1970s in Brazil and its immunopathogenesis remains poorly understood. CC-chemokine receptor 5 (CCR5) is a chemokine receptor that binds to macrophage inflammatory protein (MIP-1 α). Both molecules are associated with inflammatory cells migration during infections. In this study, we demonstrated the importance of the CCR5 and MIP-1 α, in the outcome of viral encephalitis of ROCV-infected mice. CCR5 and MIP-1 α knockout mice survived longer than wild-type (WT) ROCV-infected animals. In addition, knockout mice had reduced inflammation in the brain. Assessment of brain viral load showed mice virus detection five days post-infection in wild-type and CCR5-/- mice, while MIP-1 α-/- mice had lower viral loads seven days post-infection. Knockout mice required a higher lethal dose than wild-type mice as well. The CCR5/MIP-1 α axis may contribute to migration of infected cells to the brain and consequently affect the pathogenesis during ROCV infection.

  16. CCR3 expression induced by IL-2 and IL-4 functioning as a death receptor for B cells

    DEFF Research Database (Denmark)

    Jinquan, Tan; Jacobi, Henrik H; Jing, Chen

    2003-01-01

    We report that CCR3 is not expressed on freshly isolated peripheral and germinal B cells, but is up-regulated after stimulation with IL-2 and IL-4 (approximately 98% CCR3(+)). Ligation of CCR3 by eotaxin/chemokine ligand (CCL) 11 induces apoptosis in IL-2- and IL-4-stimulated primary CD19......-4, and eotaxin/CCL11 (88% CD95 and 84% CD95L). We therefore propose that ligation of such newly induced CCR3 on peripheral and germinal B cells by eotaxin/CCL11 leads to the enhanced levels of CD95 and CD95L expression. Ligation of CD95 by its CD95L expressed on neigboring B cells triggers relevant....... Interaction between CCR3 and eotaxin/CCL11 may, besides promoting allergic reactions, drive activated B cells to apoptosis, thereby reducing levels of Ig production, including IgE, and consequently limit the development of the humoral immune response. The apoptotic action of eotaxin/CCL11 suggests...

  17. Investigation of Chemokine Receptor CCR2V64Il Gene Polymorphism and Migraine without Aura in the Iranian Population

    Directory of Open Access Journals (Sweden)

    Alireza Zandifar

    2013-01-01

    Full Text Available Background and Objectives. Migraine is a multifactorial common neurovascular disease with a polygenic inheritance. Inflammation plays an important part in migraine pathophysiology. C-C chemokine receptor 2 (CCR2 is an important chemokine for monocyte aggregation and transendothelial monocyte migration. The aim of our study was to investigate the association of migraine with CCR2V64Il polymorphism in the Iranian population. Methods. We assessed 103 patients with newly diagnosed migraine and 100 healthy subjects. Genomic DNA samples were extracted from peripheral blood and genotypes of CCR2V64Il gene polymorphism were determined. For measuring the severity of headache, every patient filled out the MIGSEV questionnaire. Results. There were no significant differences in the distribution of both 64Il allele and heterozygote (GA genotype of CCR2 gene polymorphism (P=0.396; OR=0.92, 95% CI = 0.50–1.67 and P=0.388; OR=0.91, 95% CI = 0.47–1.73, resp. between case and control groups. There was no significant difference of alleles frequency between three grades of MIGSEV (P=0.922. Conclusions. In conclusion our results revealed no association between CCR2V64Il polymorphism and susceptibility to migraine and also headache severity in the Iranian population.

  18. High frequency of the CCR5delta32 variant among individuals from an admixed Brazilian population with sickle cell anemia

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    J.A.B. Chies

    2003-01-01

    Full Text Available Homozygous sickle cell disease (SCD has a wide spectrum of clinical manifestations. In Brazil, the main cause of death of individuals with SCD is recurrent infection. The CCR5delta32 allele, which confers relative resistance to macrophage-tropic HIV virus infection, probably has reached its frequency and world distribution due to other pathogens that target macrophage in European populations. In the present investigation a relatively higher prevalence (5.1% of the CCR5delta32 allele was identified, by PCR amplification using specific primers, in 79 SCD patients when compared to healthy controls (1.3% with the same ethnic background (Afro-Brazilians. Based on a hypothesis that considers SCD as a chronic inflammatory condition, and since the CCR5 chemokine receptor is involved in directing a Th1-type immune response, we suggest that a Th1/Th2 balance can influence the morbidity of SCD. If the presence of the null CCR5delta32 allele results in a reduction of the chronic inflammation state present in SCD patients, this could lead to differential survival of SCD individuals who are carriers of the CCR5delta32 allele. This differential survival could be due to the development of less severe infections and consequently reduced or less severe vaso-occlusive crises.

  19. The role of MCP-1-CCR2 ligand-receptor axis in chondrocyte degradation and disease progress in knee osteoarthritis

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    Yuan-kun Xu

    Full Text Available BACKGROUND: Osteoarthritis (OA is a common arthritic disease and multifactorial whole-joint disease. Interactions of chemokines and OA is inadequately documented RESULTS: In vivo and in vitro studies were conducted to investigate monocyte chemoattractant protein 1 (MCP-1 and receptor chemokine (C-C motif receptor 2 (CCR2 in chondrocyte degradation and cartilage degeneration. Chondrocytes from 16 OA patients and 6 normal controls were involved in this study. After stimulation of MCP-1, the expression of MCP-1 and CCR2 increased significantly (P < 0.001 and the expression of MMP-13 also increased (P < 0.05. MCP-1 stimulation also induced (or enhanced the apoptosis of OA chondrocytes (P < 0.05. Additionally, the degradation of cartilage matrix markers (metalloproteinase 3 and 13, MMP3 and MMP13 in the culture medium of normal chondrocytes was also assessed. Furthermore, intra-articular injection of MCP-1 in mouse knees induced cartilage degradation and the CCR2 antagonist did not impede cartilage destroy in rats knees of monosodium iodoacetate (MIA model CONCLUSIONS: The results of this study demonstrate that the MCP-1-CCR2 ligand-receptor axis plays a special role in the initiation and progression of OA pathology. Patients with ambiguous etiology can gain some insight from the MCP-1-CCR2 ligand-receptor axis

  20. Determination of nuclear moments and nuclear radii changes of the metastable silverisotopes sup(108m)Ag and sup(110m)Ag from the hyperfine structure of silver-I-resonance lines

    International Nuclear Information System (INIS)

    Meier, T.

    1973-01-01

    The hyperfine structure of the resonance lines of the metastable silver isotopes sup(108m), sup(110m)Ag were investigated by means of optical interference spectroscopy. Both radioactive silver isotopes were obtained by irradiating isotope-pure 107 Ag or 109 Ag with neutrons in the reactor. In spite of the slight enrichment of the isotopes to be investigated compared to the stable isotopes ( [de

  1. CCL2 binding is CCR2 independent in primary adult human astrocytes.

    Science.gov (United States)

    Fouillet, A; Mawson, J; Suliman, O; Sharrack, B; Romero, I A; Woodroofe, M N

    2012-02-09

    Chemokines are low relative molecular mass proteins, which have chemoattractant actions on many cell types. The chemokine, CCL2, has been shown to play a major role in the recruitment of monocytes in central nervous system (CNS) lesions in multiple sclerosis (MS). Since resident astrocytes constitute a major source of chemokine synthesis including CCL2, we were interested to assess the regulation of CCL2 by astrocytes. We showed that CCL2 bound to the cell surface of astrocytes and binding was not modulated by inflammatory conditions. However, CCR2 protein was not detected nor was activation of the classical CCR2 downstream signaling pathways. Recent studies have shown that non-signaling decoy chemokine receptors bind and modulate the expression of chemokines at site of inflammation. Here, we show that the D6 chemokine decoy receptor is constitutively expressed by primary human adult astrocytes at both mRNA and protein level. In addition, CCL3, which binds to D6, but not CCL19, which does not bind to D6, displaced CCL2 binding to astrocytes; indicating that CCL2 may bind to this cell type via the D6 receptor. Our results suggest that CCL2 binding to primary adult human astrocytes is CCR2-independent and is likely to be mediated via the D6 decoy chemokine receptor. Therefore we propose that astrocytes are implicated in both the establishment of chemokine gradients for the migration of leukocytes into and within the CNS and in the regulation of CCL2 levels at inflammatory sites in the CNS. Copyright © 2011 Elsevier B.V. All rights reserved.

  2. De-novo Collateral Formation Following Acute Myocardial Infarction: Dependence on CCR2+ Bone Marrow Cells

    Science.gov (United States)

    Zhang, Hua; Faber, James E

    2015-01-01

    Wide variation exists in the extent (number and diameter) of native pre-existing collaterals in tissues of different strains of mice, with supportive indirect evidence recently appearing for humans. This variation is a major determinant of the wide variation in severity of tissue injury in occlusive vascular disease. Whether such genetic-dependent variation also exists in the heart is unknown because no model exists for study of mouse coronary collaterals. Also owing to methodological limitations, it is not known if ischemia can induce new coronary collaterals to form (“neo-collaterals”) versus remodeling of pre-existing ones. The present study sought to develop a model to study coronary collaterals in mice, determine whether neo-collateral formation occurs, and investigate the responsible mechanisms. Four strains with known rank-ordered differences in collateral extent in brain and skeletal muscle were studied: C57BLKS>C57BL/6>A/J>BALB/c. Unexpectedly, these and 5 additional strains lacked native coronary collaterals. However after ligation, neo-collaterals formed rapidly within 1-to-2 days, reaching their maximum extent in ≤ 7 days. Rank-order for neo-collateral formation differed from the above: C57BL/6>BALB/c>C57BLKS>A/J. Collateral network conductance, infarct volume−1, and contractile function followed this same rank-order. Neo-collateral formation and collateral conductance were reduced and infarct volume increased in MCP1−/− and CCR2−/− mice. Bone-marrow transplant rescued collateral formation in CCR2−/− mice. Involvement of fractalkine→CX3CR1 signaling and endothelial cell proliferation were also identified. This study introduces a model for investigating the coronary collateral circulation in mice, demonstrates that neocollaterals form rapidly after coronary occlusion, and finds that MCP→CCR2-mediated recruitment of myeloid cells is required for this process. PMID:26254180

  3. Consequences of ChemR23 heteromerization with the chemokine receptors CXCR4 and CCR7.

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    Cédric de Poorter

    Full Text Available Recent studies have shown that heteromerization of the chemokine receptors CCR2, CCR5 and CXCR4 is associated to negative binding cooperativity. In the present study, we build on these previous results, and investigate the consequences of chemokine receptor heteromerization with ChemR23, the receptor of chemerin, a leukocyte chemoattractant protein structurally unrelated to chemokines. We show, using BRET and HTRF assays, that ChemR23 forms homomers, and provide data suggesting that ChemR23 also forms heteromers with the chemokine receptors CCR7 and CXCR4. As previously described for other chemokine receptor heteromers, negative binding cooperativity was detected between ChemR23 and chemokine receptors, i.e. the ligands of one receptor competed for the binding of a specific tracer of the other. We also showed, using mouse bone marrow-derived dendritic cells prepared from wild-type and ChemR23 knockout mice, that ChemR23-specific ligands cross-inhibited CXCL12 binding on CXCR4 in a ChemR23-dependent manner, supporting the relevance of the ChemR23/CXCR4 interaction in native leukocytes. Finally, and in contrast to the situation encountered for other previously characterized CXCR4 heteromers, we showed that the CXCR4-specific antagonist AMD3100 did not cross-inhibit chemerin binding in cells co-expressing ChemR23 and CXCR4, demonstrating that cross-regulation by AMD3100 depends on the nature of receptor partners with which CXCR4 is co-expressed.

  4. Consequences of ChemR23 heteromerization with the chemokine receptors CXCR4 and CCR7.

    Science.gov (United States)

    de Poorter, Cédric; Baertsoen, Kevin; Lannoy, Vincent; Parmentier, Marc; Springael, Jean-Yves

    2013-01-01

    Recent studies have shown that heteromerization of the chemokine receptors CCR2, CCR5 and CXCR4 is associated to negative binding cooperativity. In the present study, we build on these previous results, and investigate the consequences of chemokine receptor heteromerization with ChemR23, the receptor of chemerin, a leukocyte chemoattractant protein structurally unrelated to chemokines. We show, using BRET and HTRF assays, that ChemR23 forms homomers, and provide data suggesting that ChemR23 also forms heteromers with the chemokine receptors CCR7 and CXCR4. As previously described for other chemokine receptor heteromers, negative binding cooperativity was detected between ChemR23 and chemokine receptors, i.e. the ligands of one receptor competed for the binding of a specific tracer of the other. We also showed, using mouse bone marrow-derived dendritic cells prepared from wild-type and ChemR23 knockout mice, that ChemR23-specific ligands cross-inhibited CXCL12 binding on CXCR4 in a ChemR23-dependent manner, supporting the relevance of the ChemR23/CXCR4 interaction in native leukocytes. Finally, and in contrast to the situation encountered for other previously characterized CXCR4 heteromers, we showed that the CXCR4-specific antagonist AMD3100 did not cross-inhibit chemerin binding in cells co-expressing ChemR23 and CXCR4, demonstrating that cross-regulation by AMD3100 depends on the nature of receptor partners with which CXCR4 is co-expressed.

  5. The chemokine receptor CCR1 is identified in mast cell-derived exosomes.

    Science.gov (United States)

    Liang, Yuting; Qiao, Longwei; Peng, Xia; Cui, Zelin; Yin, Yue; Liao, Huanjin; Jiang, Min; Li, Li

    2018-01-01

    Mast cells are important effector cells of the immune system, and mast cell-derived exosomes carrying RNAs play a role in immune regulation. However, the molecular function of mast cell-derived exosomes is currently unknown, and here, we identify differentially expressed genes (DEGs) in mast cells and exosomes. We isolated mast cells derived exosomes through differential centrifugation and screened the DEGs from mast cell-derived exosomes, using the GSE25330 array dataset downloaded from the Gene Expression Omnibus database. Biochemical pathways were analyzed by Gene ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway on the online tool DAVID. DEGs-associated protein-protein interaction networks (PPIs) were constructed using the STRING database and Cytoscape software. The genes identified from these bioinformatics analyses were verified by qRT-PCR and Western blot in mast cells and exosomes. We identified 2121 DEGs (843 up and 1278 down-regulated genes) in HMC-1 cell-derived exosomes and HMC-1 cells. The up-regulated DEGs were classified into two significant modules. The chemokine receptor CCR1 was screened as a hub gene and enriched in cytokine-mediated signaling pathway in module one. Seven genes, including CCR1, CD9, KIT, TGFBR1, TLR9, TPSAB1 and TPSB2 were screened and validated through qRT-PCR analysis. We have achieved a comprehensive view of the pivotal genes and pathways in mast cells and exosomes and identified CCR1 as a hub gene in mast cell-derived exosomes. Our results provide novel clues with respect to the biological processes through which mast cell-derived exosomes modulate immune responses.

  6. Expression analysis of cinnamoyl-CoA reductase (CCR) gene in developing seedlings of Leucaena leucocephala: a pulp yielding tree species.

    Science.gov (United States)

    Srivastava, Sameer; Gupta, Ranadheer K; Arha, Manish; Vishwakarma, Rishi K; Rawal, Shuban K; Kavi Kishor, P B; Khan, Bashir M

    2011-02-01

    Removal of lignin is a major hurdle for obtaining good quality pulp. Leucaena leucocephala (subabul) is extensively used in paper industry in India; therefore, as a first step to generate transgenic plants with low lignin content, cDNA and genomic clones of CCR gene were isolated and characterized. The cDNA encoding CCR (EC 1.2.1.44) was designated as Ll-CCR; the sequence analysis revealed an Open Reading Frame (ORF) of 1005 bp. Phylogenetic analysis showed that Ll-CCR sequence is highly homologous to CCRs from other dicot plants. The 2992 bp genomic clone of Leucaena CCR consists of 5 exons and 4 introns. The haploid genome of L. leucocephala contains two copies as revealed by DNA blot hybridization. Ll-CCR gene was over-expressed in Escherichia coli, which showed a molecular mass of approximately 38 kDa. Protein blot analysis revealed that Ll-CCR protein is expressed at higher levels in root and in stem, but undetectable in leaf tissues. Expression of CCR gene in Leucaena increased up to 15 d in case of roots and stem as revealed by QRT-PCR studies in 0-15 d old seedlings. ELISA based studies of extractable CCR protein corroborated with QRT-PCR data. CCR protein was immuno-cytolocalized around xylem tissue. Lignin estimation and expression studies of 5, 10 and 15 d old stem and root suggest that CCR expression correlates with quantity of lignin produced, which makes it a good target for antisense down regulation for producing designer species for paper industry. Copyright © 2010 Elsevier Masson SAS. All rights reserved.

  7. Figure-ground processing during fixational saccades in V1: indication for higher-order stability.

    Science.gov (United States)

    Gilad, Ariel; Pesoa, Yair; Ayzenshtat, Inbal; Slovin, Hamutal

    2014-02-26

    In a typical visual scene we continuously perceive a "figure" that is segregated from the surrounding "background" despite ongoing microsaccades and small saccades that are performed when attempting fixation (fixational saccades [FSs]). Previously reported neuronal correlates of figure-ground (FG) segregation in the primary visual cortex (V1) showed enhanced activity in the "figure" along with suppressed activity in the noisy "background." However, it is unknown how this FG modulation in V1 is affected by FSs. To investigate this question, we trained two monkeys to detect a contour embedded in a noisy background while simultaneously imaging V1 using voltage-sensitive dyes. During stimulus presentation, the monkeys typically performed 1-3 FSs, which displaced the contour over the retina. Using eye position and a 2D analytical model to map the stimulus onto V1, we were able to compute FG modulation before and after each FS. On the spatial cortical scale, we found that, after each FS, FG modulation follows the stimulus retinal displacement and "hops" within the V1 retinotopic map, suggesting visual instability. On the temporal scale, FG modulation is initiated in the new retinotopic position before it disappeared from the old retinotopic position. Moreover, the FG modulation developed faster after an FS, compared with after stimulus onset, which may contribute to visual stability of FG segregation, along the timeline of stimulus presentation. Therefore, despite spatial discontinuity of FG modulation in V1, the higher-order stability of FG modulation along time may enable our stable and continuous perception.

  8. HIV-1 Tropism Testing and Clinical Management of CCR5 Antagonists: Quebec Review and Recommendations

    Directory of Open Access Journals (Sweden)

    Cécile Tremblay

    2013-01-01

    Full Text Available HIV-1 tropism assays play a crucial role in determining the response to CCR5 receptor antagonists. Initially, phenotypic tests were used, but limited access to these tests prompted the development of alternative strategies. Recently, genotyping tropism has been validated using a Canadian technology in clinical trials investigating the use of maraviroc in both experienced and treatment-naive patients. The present guidelines review the evidence supporting the use of genotypic assays and provide recommendations regarding tropism testing in daily clinical management.

  9. Biased signaling of G protein-coupled receptors - From a chemokine receptor CCR7 perspective

    DEFF Research Database (Denmark)

    Jørgensen, Astrid Sissel; Rosenkilde, Mette M; Hjortø, Gertrud M

    2018-01-01

    of CCL21 displays an extraordinarily strong glycosaminoglycan (GAG) binding, CCR7 plays a central role in coordinating the meeting between mature antigen presenting DCs and naïve T-cells which normally takes place in the lymph nodes (LNs). This process is a prerequisite for the initiation of an antigen...... the cell-based immune system is controlled. Bias comes in three forms; ligand-, receptor- and tissue-bias. Biased signaling is increasingly being recognized as playing an important role in contributing to the fine-tuned coordination of immune cell chemotaxis. In the current review we discuss the recent...

  10. Infarction of renal transplant with extrarenal excretion of Tc-99m MAG3 demonstrated by renal scintigraphy

    International Nuclear Information System (INIS)

    Lim, Seok Tae; Kim, Min Woo; Sohn, Myung Hee

    2003-01-01

    A 38-year-old woman with end stage renal disease received a living related donor-renal transplant to the right iliac fossa. She developed anuria a week later. Tc-99m MAG 3 renal scintigraphy demonstrated no perfusion, uptake, or excretion of the radioactive tracer from the renal transplant. The expected area of the renal allograft appeared as a photopenic area with increased rim activity. The gallbladder and bowel activities were observed on delayed images at 24 hours. There was no blood flow within the renal artery on renal doppler examination. This case shows total absence of perfusion and function in the infarcted renal transplant with extrarenal excretion of Tc-99m MAG 3 caused by acute renal artery thrombosis

  11. Preliminary results of scoop samples analysis from reactor pressure vessels of Bohunice V-1 NPP

    International Nuclear Information System (INIS)

    Kupca, L.

    1997-01-01

    In the paper are presented the main goals and results from the scoop specimen analysis performed on the both RPVs WWER-440/230 in Jaslovske Bohunice V-1 NPPs. Main tasks of this complex activity were: model experiments for analysis procedures optimisation; chemical analysis; hardness measurements on the RPV and bulk samples; microstructure analysis; scanning electron microscope and microprobe analysis; gamma spectrometry; brittle fracture temperature evaluation; trends of brittle fracture temperature growth after annealing procedure. In conclusions and recommendations are discussed the planned activities in the field of both RPVs integrity evaluation for the future operation of the NPP Jaslovske Bohunice V-1. (author)

  12. Kinetics of manganese in MAG/MIG welding with a 18/8/6 wire

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    Tušek, Janez

    2001-06-01

    Full Text Available The paper deals with a study of MAG/MIG welding of low-alloy ferritic steel and highalloy austenitic steel with a 18/8/6 wire. Manganese burn-off from the wire in welding a single-V butt weld was studied. It was found that manganese burns off in the arc during melting of a droplet at the wire end, and from the weld pool during weld formation. The range of manganese burn-off depends mainly on the type of shielding gas used and the arc length, i.e., from the arc voltage. The manganese burn-off increases with an increase of the content of active gases, i.e., CO2 and O2, in the neutral gas, i.e., argon. It also increases with an increase in arc voltage. The longer the welding arc, the longer exposition of the filler material to the welding arc and the wider the penetration, which allows manganese vapours to evaporate from the weld pool. The most important finding is that manganese burn-off from the 18/8/6 wire during welding of austenitic stainless steel with low-alloy ferritic steel is considerably strong, i.e., from 20% to 30%; nevertheless the wire concerned is perfectly suitable for welding of different types of steel.

    El artículo describe el estudio de un acero ferrítico poco aleado con un acero austenítico altamente aleado con el alambre 18/8/6 mediante el procedimiento MAG/MIG. Se ha investigado el consumo del manganeso del alambre durante la soldadura a tope con la preparación en V. Con los análisis se ha comprobado que el manganeso se consume en el arco desde la formación de la gota en la punta del alambre hasta la solidificación del metal aportado fundido. La cantidad perdida del manganeso depende, sobre todo, del tipo del gas de protección y de la longitud del arco, esto es, de la tensión convencional en el arco. Con el aumento de los gases activos (CO2 y O2 respecto al gas neutro argon, el consumo del manganeso va aumentando. También se observó que el consumo del manganeso va

  13. CCR2+ Monocyte-Derived Infiltrating Macrophages Are Required for Adverse Cardiac Remodeling During Pressure Overload

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    Bindiya Patel, PhD

    2018-04-01

    Full Text Available Summary: Although chronic inflammation is a central feature of heart failure (HF, the immune cell profiles differ with different underlying causes. This suggests that for immunomodulatory therapy in HF to be successful, it needs to be tailored to the specific etiology. Here, the authors demonstrate that monocyte-derived C-C chemokine receptor 2 (CCR2+ macrophages infiltrate the heart early during pressure overload in mice, and that blocking this response either pharmacologically or with antibody-mediated CCR2+ monocyte depletion alleviates late pathological left ventricular remodeling and dysfunction, T-cell expansion, and cardiac fibrosis. Hence, suppression of CCR2+ monocytes/macrophages may be an important immunomodulatory therapeutic target to ameliorate pressure-overload HF. Key Words: cardiac remodeling, heart failure, inflammation, macrophages, T cells

  14. Mechanical Characteristic of Remanufacturing of FV520B Precipitation Hardening Stainless Steel Using MAG Surfacing Deposition

    Directory of Open Access Journals (Sweden)

    LIU Jian

    2017-10-01

    Full Text Available Surfacing deposition forming method was adopted to carry out remanufacturing experiment of FV520B precipitation hardening stainless steel. Then the mechanical property characteristic of the remanufacturing layer was tested and studied, contrasted with the corresponding property of substrate. The results show that the remanufacturing layer, formed with MAG surfacing of FV520B precipitation hardening stainless steel has mechanical characteristic with high strength and hardness, the tensile strength reaches 1195MPa, exceeds 1092MPa of substrate, yield strength is 776MPa and average hardness is 336HV, is close to the corresponding property of substrate which is 859MPa and 353HV respectively; however, the elongation and impact toughness of the remanufacturing layer is merely 8.92% and 61J/cm2 respectively, it has a large gap with the corresponding property 19.72% and 144J/cm2 respectively of substrate. Fracture and microstructure analysis on specimens shows that the microstructure of remanufacturing layer is fast cooling non-equilibrium crystallized lath martensite, and carbide precipitated strengthening phase such as NbC, MoC, M23C6,etc, which is the reason that remanufacturing layer has high strength and high hardness. But as lack of aging treatment and Cu strengthening phase, and the weak interface between contaminating brittle phase or large size spherical particles and substrate will deteriorate the deformability and induce stress concentration and cracking when the material is load-carrying, and is the main reason of the remanufacturing layer having lower static tensile elongation and impact toughness.

  15. CalMagNet – an array of search coil magnetometers monitoring ultra low frequency activity in California

    Directory of Open Access Journals (Sweden)

    C. Dunson

    2008-04-01

    Full Text Available The California Magnetometer Network (CalMagNet consists of sixty-eight triaxial search-coil magnetometer systems measuring Ultra Low Frequency (ULF, 0.001–16 Hz, magnetic field fluctuations in California. CalMagNet provides data for comprehensive multi-point measurements of specific events in the Pc 1–Pc 5 range at mid-latitudes as well as a systematic, long-term study of ULF signals in active fault regions in California. Typical events include geomagnetic micropulsations and spectral resonant structures associated with the ionospheric Alfvén resonator. This paper provides a technical overview of the CalMagNet sensors and data processing systems. The network is composed of ten reference stations and fifty-eight local monitoring stations. The primary instruments at each site are three orthogonal induction coil magnetometers. A geophone monitors local site vibration. The systems are designed for future sensor expansion and include resources for monitoring four additional channels. Data is currently sampled at 32 samples per second with a 24-bit converter and time tagged with a GPS-based timing system. Several examples of representative magnetic fluctuations and signals as measured by the array are given.

  16. Imprinting of CCR9 on CD4 T cells requires IL-4 signaling on mesenteric lymph node dendritic cells.

    Science.gov (United States)

    Elgueta, Raul; Sepulveda, Fernando E; Vilches, Felipe; Vargas, Leonardo; Mora, J Rodrigo; Bono, Maria Rosa; Rosemblatt, Mario

    2008-05-15

    It has recently been shown that IL-4 can educate dendritic cells (DC) to differentially affect T cell effector activity. In this study, we show that IL-4 can also act upon DC to instruct naive T cells to express the gut-associated homing receptor CCR9. Thus, effector T cells generated after coculture with mesenteric lymph node (MLN)-DC show a higher expression of CCR9 when activated in the presence of IL-4. In contrast, IL-4 had no effect on CCR9 expression when naive T cells were polyclonally activated in the absence of MLN-DC, suggesting that the effect of IL-4 on CCR9 expression passed through DC. Indeed, T cells activated by MLN-DC from IL-4Ralpha(-/-) mice showed a much lower CCR9 expression and a greatly reduced migration to the small intestine than T cells activated by wild-type MLN-DC even in the presence of IL-4. Consistent with the finding that the vitamin A metabolite retinoic acid (RA) induces gut-homing molecules on T cells, we further demonstrate that IL-4 up-regulated retinaldehyde dehydrogenase 2 mRNA on MLN-DC, a critical enzyme involved in the synthesis of RA. Moreover, LE135, a RA receptor antagonist, blocked the increased expression of CCR9 driven by IL-4-treated MLN-DC. Thus, besides the direct effect of RA on T cell gut tropism, our results show that the induction of a gut-homing phenotype on CD4(+) T cells is also influenced by the effect of IL-4 on gut-associated DC.

  17. Gas6 Promotes Inflammatory (CCR2hiCX3CR1lo) Monocyte Recruitment in Venous Thrombosis.

    Science.gov (United States)

    Laurance, Sandrine; Bertin, François-René; Ebrahimian, Talin; Kassim, Yusra; Rys, Ryan N; Lehoux, Stéphanie; Lemarié, Catherine A; Blostein, Mark D

    2017-07-01

    Coagulation and inflammation are inter-related. Gas6 (growth arrest-specific 6) promotes venous thrombosis and participates to inflammation through endothelial-innate immune cell interactions. Innate immune cells can provide the initiating stimulus for venous thrombus development. We hypothesize that Gas6 promotes monocyte recruitment during venous thrombosis. Deep venous thrombosis was induced in wild-type and Gas6-deficient (-/-) mice using 5% FeCl 3 and flow reduction in the inferior vena cava. Total monocyte depletion was achieved by injection of clodronate before deep venous thrombosis. Inflammatory monocytes were depleted using an anti-C-C chemokine receptor type 2 (CCR2) antibody. Similarly, injection of an anti-chemokine ligand 2 (CCL2) antibody induced CCL2 depletion. Flow cytometry and immunofluorescence were used to characterize the monocytes recruited to the thrombus. In vivo, absence of Gas6 was associated with a reduction of monocyte recruitment in both deep venous thrombosis models. Global monocyte depletion by clodronate leads to smaller thrombi in wild-type mice. Compared with wild type, the thrombi from Gas6 -/- mice contain less inflammatory (CCR2 hi CX 3 CR1 lo ) monocytes, consistent with a Gas6-dependent recruitment of this monocyte subset. Correspondingly, selective depletion of CCR2 hi CX 3 CR1 lo monocytes reduced the formation of venous thrombi in wild-type mice demonstrating a predominant role of the inflammatory monocytes in thrombosis. In vitro, the expression of both CCR2 and CCL2 were Gas6 dependent in monocytes and endothelial cells, respectively, impacting monocyte migration. Moreover, Gas6-dependent CCL2 expression and monocyte migration were mediated via JNK (c-Jun N-terminal kinase). This study demonstrates that Gas6 specifically promotes the recruitment of inflammatory CCR2 hi CX 3 CR1 lo monocytes through the regulation of both CCR2 and CCL2 during deep venous thrombosis. © 2017 American Heart Association, Inc.

  18. The CC-chemokine receptor 5 (CCR5) is a marker of, but not essential for the development of human Th1 cells

    DEFF Research Database (Denmark)

    Odum, Niels; Bregenholt, S; Eriksen, K W

    1999-01-01

    The CC-chemokine receptor 5 (CCR5) has recently been described as a surface marker of human T cells producing type 1 (Th1) cytokines. Here we confirm that CCR5 is expressed on human Th1 but not on Th2 T-cell clones. Using intracellular cytokine staining, we show that alloantigen specific CD4+ T...

  19. Functional analysis of the CC chemokine receptor 5 (CCR5) on virus-specific CD8+ T cells following coronavirus infection of the central nervous system

    International Nuclear Information System (INIS)

    Glass, William G.; Lane, Thomas E.

    2003-01-01

    Intracranial infection of C57BL/6 mice with mouse hepatitis virus (MHV) results in an acute encephalomyelitis followed by a demyelinating disease similar in pathology to the human disease multiple sclerosis (MS). T cells participate in both defense and disease progression following MHV infection. Expression of chemokine receptors on activated T cells is important in allowing these cells to traffic into and accumulate within the central nervous system (CNS) of MHV-infected mice. The present study evaluated the contributions of CCR5 to the activation and trafficking of virus-specific CD8 + T cells into the MHV-infected CNS mice. Comparable numbers of virus-specific CD8 + T cells derived from immunized CCR5 +/+ or CCR5 -/- mice were present within the CNS of MHV-infected RAG1 -/- mice following adoptive transfer, indicating that CCR5 is not required for trafficking of these cells into the CNS. RAG1 -/- recipients of CCR5 -/- -derived CD8 + T cells exhibited a modest, yet significant (P ≤ 0.05), reduction in viral burden within the brain which correlated with increased CTL activity and IFN-γ expression. Histological analysis of RAG1 -/- recipients of either CCR5 +/+ or CCR5 -/- -derived CD8 + T cells revealed only focal areas of demyelination with no significant differences in white matter destruction. These data indicate that CCR5 signaling on CD8 + T cells modulates antiviral activities but is not essential for entry into the CNS

  20. Gating function of isoleucine-116 in TM-3 (position III:16/3.40) for the activity state of the CC-chemokine receptor 5 (CCR5)

    DEFF Research Database (Denmark)

    Steen, A; Sparre-Ulrich, A H; Thiele, Stefanie

    2014-01-01

    TM receptors - it is a leucine indicating an altered function. Here, we describe the significance of this position and its possible interaction with TM-3 for CCR5 activity. EXPERIMENTAL APPROACH: The effects of [L203F]-CCR5 in TM-5 (position V:13/5.47), [I116A]-CCR5 in TM-3 (III:16/3.40) and [L203F...... ) with a threefold increase in agonist potency. In silico, [I116A]-CCR5 switched χ1-angle in [L203F]-CCR5. Furthermore, [I116A]-CCR5 was constitutively active to a similar degree as [L203F]-CCR5. Tyr(244) in TM-6 (VI:09/6.44) moved towards TM-5 in silico, consistent with its previously shown function for CCR5...... in the active state, a mechanism proposed previously for the β2 -adrenoceptor. The results provide an understanding of chemokine receptor function and thereby information for the development of biased and non-biased antagonists and inverse agonists....

  1. The Isolation of Novel Phage Display-Derived Human Recombinant Antibodies Against CCR5, the Major Co-Receptor of HIV

    Science.gov (United States)

    Shimoni, Moria; Herschhorn, Alon; Britan-Rosich, Yelena; Kotler, Moshe; Benhar, Itai

    2013-01-01

    Abstract Selecting for antibodies against specific cell-surface proteins is a difficult task due to many unrelated proteins that are expressed on the cell surface. Here, we describe a method to screen antibody-presenting phage libraries against native cell-surface proteins. We applied this method to isolate antibodies that selectively recognize CCR5, which is the major co-receptor for HIV entry (consequently, playing a pivotal role in HIV transmission and pathogenesis). We employed a phage screening strategy by using cells that co-express GFP and CCR5, along with an excess of control cells that do not express these proteins (and are otherwise identical to the CCR5-expressing cells). These control cells are intended to remove most of the phages that bind the cells nonspecifically; thus leading to an enrichment of the phages presenting anti-CCR5-specific antibodies. Subsequently, the CCR5-presenting cells were quantitatively sorted by flow cytometry, and the bound phages were eluted, amplified, and used for further successive selection rounds. Several different clones of human single-chain Fv antibodies that interact with CCR5-expressing cells were identified. The most specific monoclonal antibody was converted to a full-length IgG and bound the second extracellular loop of CCR5. The experimental approach presented herein for screening for CCR5-specific antibodies can be applicable to screen antibody-presenting phage libraries against any cell-surface expressed protein of interest. PMID:23941674

  2. The herpesvirus 8-encoded chemokine vMIP-II, but not the poxvirus-encoded chemokine MC148, inhibits the CCR10 receptor

    DEFF Research Database (Denmark)

    Lüttichau, H R; Lewis, I C; Gerstoft, J

    2001-01-01

    The viral chemokine antagonist vMIP-II encoded by human herpesvirus 8 (HHV8) and MC148 encoded by the poxvirus - Molluscum contagiosum - were tested against the newly identified chemokine receptor CCR10. As the CCR10 ligand ESkine / CCL27 had the highest identity to MC148 and because both...

  3. Optical, mechanical and TEM assessment of titania-doped Bi2V1 ...

    Indian Academy of Sciences (India)

    2016-08-26

    Aug 26, 2016 ... Home; Journals; Bulletin of Materials Science; Volume 37; Issue 7. Optical, mechanical and TEM assessment of titania-doped Bi2V1−TiO5.5−δ bismuth vanadate oxides. Gurbinder Kaur Gary Pickrell Vishal Kumar Om Prakash Pandey Kulvir Singh Daniel Homa. Volume 37 Issue 7 December 2014 pp ...

  4. Visual recognition memory, manifest as long-term habituation, requires synaptic plasticity in V1

    Science.gov (United States)

    Cooke, Sam F.; Komorowski, Robert W.; Kaplan, Eitan S.; Gavornik, Jeffrey P.; Bear, Mark F.

    2015-01-01

    Familiarity with stimuli that bring neither reward nor punishment, manifested through behavioural habituation, enables organisms to detect novelty and devote cognition to important elements of the environment. Here we describe in mice a form of long-term behavioural habituation to visual grating stimuli that is selective for stimulus orientation. Orientation-selective habituation (OSH) can be observed both in exploratory behaviour in an open arena, and in a stereotyped motor response to visual stimuli in head-restrained mice. We show that the latter behavioural response, termed a vidget, requires V1. Parallel electrophysiological recordings in V1 reveal that plasticity, in the form of stimulus-selective response potentiation (SRP), occurs in layer 4 of V1 as OSH develops. Local manipulations of V1 that prevent and reverse electrophysiological modifications likewise prevent and reverse memory demonstrated behaviourally. These findings suggest that a form of long-term visual recognition memory is stored via synaptic plasticity in primary sensory cortex. PMID:25599221

  5. Combined sodium ion sensitivity in agonist binding and internalization of vasopressin V1b receptors.

    Science.gov (United States)

    Koshimizu, Taka-Aki; Kashiwazaki, Aki; Taniguchi, Junichi

    2016-05-03

    Reducing Na(+) in the extracellular environment may lead to two beneficial effects for increasing agonist binding to cell surface G-protein coupled receptors (GPCRs): reduction of Na(+)-mediated binding block and reduce of receptor internalization. However, such combined effects have not been explored. We used Chinese Hamster Ovary cells expressing vasopressin V1b receptors as a model to explore Na(+) sensitivity in agonist binding and receptor internalization. Under basal conditions, a large fraction of V1b receptors is located intracellularly, and a small fraction is in the plasma membrane. Decreases in external Na(+) increased cell surface [(3)H]AVP binding and decreased receptor internalization. Substitution of Na(+) by Cs(+) or NH4(+) inhibited agonist binding. To suppress receptor internalization, the concentration of NaCl, but not of CsCl, had to be less than 50 mM, due to the high sensitivity of the internalization machinery to Na(+) over Cs(+). Iso-osmotic supplementation of glucose or NH4Cl maintained internalization of the V1b receptor, even in a low-NaCl environment. Moreover, iodide ions, which acted as a counter anion, inhibited V1b agonist binding. In summary, we found external ionic conditions that could increase the presence of high-affinity state receptors at the cell surface with minimum internalization during agonist stimulations.

  6. Analysis of the NPP-V1 primary circuit fast cooldown

    International Nuclear Information System (INIS)

    Filo, J.; Bazso, Z.; Vranka, L.

    1994-01-01

    Results of thermal-hydraulic calculations of the NPP-V1 primary circuit fast cooldown during small leakage through openings of diameter 20, 32 and 50 mm as well as analyses of cooldown following the steam pipeline break at nominal and null reactor power are given in this paper. 4 refs, 24 figs, 1 tab

  7. Immune complexes stimulate CCR7-dependent dendritic cell migration to lymph nodes

    Science.gov (United States)

    Clatworthy, Menna R.; Aronin, Caren E. Petrie; Mathews, Rebeccah J.; Morgan, Nicole; Smith, Kenneth G.C.; Germain, Ronald N.

    2014-01-01

    Antibodies are critical for defence against a variety of microbes but may also be pathogenic in some autoimmune diseases. Many effector functions of antibody are mediated by Fcγ receptors (FcγRs), which are found on most immune cells, including dendritic cells (DCs). DCs are important antigen presenting cells and play a central role in inducing antigen-specific tolerance or immunity1,2. Following antigen acquisition in peripheral tissues, DCs migrate to draining lymph nodes via lymphatics to present antigen to T cells. In this study we demonstrate that FcγR engagement by IgG immune complexes (IC) stimulates DC migration from peripheral tissues to the paracortex of draining lymph nodes. In vitro, IC-stimulated murine and human DCs showed enhanced directional migration in a CCL19 gradient and increased CCR7 expression. Using intravital two-photon microscopy, we observed that local administration of IC resulted in dermal DC mobilisation. We confirmed that dermal DC migration to lymph nodes was CCR7-dependent and increased in the absence of the inhibitory receptor, FcγRIIb. These observations have relevance to autoimmunity, because autoantibody-containing serum from mice and humans with SLE also increased dermal DC migration to lymph nodes in vivo, suggesting that this process may occur in lupus, potentially driving the inappropriate localisation of autoantigen-bearing DCs. PMID:25384086

  8. Chromatic detection from cone photoreceptors to V1 neurons to behavior in rhesus monkeys.

    Science.gov (United States)

    Hass, Charles A; Angueyra, Juan M; Lindbloom-Brown, Zachary; Rieke, Fred; Horwitz, Gregory D

    2015-01-01

    Chromatic sensitivity cannot exceed limits set by noise in the cone photoreceptors. To determine how close neurophysiological and psychophysical chromatic sensitivity come to these limits, we developed a parameter-free model of stimulus encoding in the cone outer segments, and we compared the sensitivity of the model to the psychophysical sensitivity of monkeys performing a detection task and to the sensitivity of individual V1 neurons. Modeled cones had a temporal impulse response and a noise power spectrum that were derived from in vitro recordings of macaque cones, and V1 recordings were made during performance of the detection task. The sensitivity of the simulated cone mosaic, the V1 neurons, and the monkeys were tightly yoked for low-spatiotemporal-frequency isoluminant modulations, indicating high-fidelity signal transmission for this class of stimuli. Under the conditions of our experiments and the assumptions for our model, the signal-to-noise ratio for these stimuli dropped by a factor of ∼3 between the cones and perception. Populations of weakly correlated V1 neurons narrowly exceeded the monkeys' chromatic sensitivity but fell well short of the cones' chromatic sensitivity, suggesting that most of the behavior-limiting noise lies between the cone outer segments and the output of V1. The sensitivity gap between the cones and behavior for achromatic stimuli was larger than for chromatic stimuli, indicating greater postreceptoral noise. The cone mosaic model provides a means to compare visual sensitivity across disparate stimuli and to identify sources of noise that limit visual sensitivity.

  9. Functional size of human visual area V1: a neural correlate of top-down attention.

    Science.gov (United States)

    Verghese, Ashika; Kolbe, Scott C; Anderson, Andrew J; Egan, Gary F; Vidyasagar, Trichur R

    2014-06-01

    Heavy demands are placed on the brain's attentional capacity when selecting a target item in a cluttered visual scene, or when reading. It is widely accepted that such attentional selection is mediated by top-down signals from higher cortical areas to early visual areas such as the primary visual cortex (V1). Further, it has also been reported that there is considerable variation in the surface area of V1. This variation may impact on either the number or specificity of attentional feedback signals and, thereby, the efficiency of attentional mechanisms. In this study, we investigated whether individual differences between humans performing attention-demanding tasks can be related to the functional area of V1. We found that those with a larger representation in V1 of the central 12° of the visual field as measured using BOLD signals from fMRI were able to perform a serial search task at a faster rate. In line with recent suggestions of the vital role of visuo-spatial attention in reading, the speed of reading showed a strong positive correlation with the speed of visual search, although it showed little correlation with the size of V1. The results support the idea that the functional size of the primary visual cortex is an important determinant of the efficiency of selective spatial attention for simple tasks, and that the attentional processing required for complex tasks like reading are to a large extent determined by other brain areas and inter-areal connections. Copyright © 2014 Elsevier Inc. All rights reserved.

  10. The Magnetics Information Consortium (MagIC) Online Database: Uploading, Searching and Visualizing Paleomagnetic and Rock Magnetic Data

    Science.gov (United States)

    Minnett, R.; Koppers, A.; Tauxe, L.; Constable, C.; Pisarevsky, S. A.; Jackson, M.; Solheid, P.; Banerjee, S.; Johnson, C.

    2006-12-01

    The Magnetics Information Consortium (MagIC) is commissioned to implement and maintain an online portal to a relational database populated by both rock and paleomagnetic data. The goal of MagIC is to archive all measurements and the derived properties for studies of paleomagnetic directions (inclination, declination) and intensities, and for rock magnetic experiments (hysteresis, remanence, susceptibility, anisotropy). MagIC is hosted under EarthRef.org at http://earthref.org/MAGIC/ and has two search nodes, one for paleomagnetism and one for rock magnetism. Both nodes provide query building based on location, reference, methods applied, material type and geological age, as well as a visual map interface to browse and select locations. The query result set is displayed in a digestible tabular format allowing the user to descend through hierarchical levels such as from locations to sites, samples, specimens, and measurements. At each stage, the result set can be saved and, if supported by the data, can be visualized by plotting global location maps, equal area plots, or typical Zijderveld, hysteresis, and various magnetization and remanence diagrams. User contributions to the MagIC database are critical to achieving a useful research tool. We have developed a standard data and metadata template (Version 2.1) that can be used to format and upload all data at the time of publication in Earth Science journals. Software tools are provided to facilitate population of these templates within Microsoft Excel. These tools allow for the import/export of text files and provide advanced functionality to manage and edit the data, and to perform various internal checks to maintain data integrity and prepare for uploading. The MagIC Contribution Wizard at http://earthref.org/MAGIC/upload.htm executes the upload and takes only a few minutes to process several thousand data records. The standardized MagIC template files are stored in the digital archives of EarthRef.org where they

  11. CCR1

    African Journals Online (AJOL)

    inflammatory protein II; Bioinformatics; Protease digestion; HEK293 cells; Radioligand binding. Tropical .... Cell membranes ... binding was counted using a scintillation counter. ... any remaining red blood cells. .... *Denotes the most stable peptide, C18P; amount presents .... korthalsii methanol extract on human peripheral.

  12. Cyclooxygenase-2 up-regulates CCR7 expression via AKT-mediated phosphorylation and activation of Sp1 in breast cancer cells.

    Science.gov (United States)

    Chuang, Chun-Wei; Pan, Mei-Ren; Hou, Ming-Feng; Hung, Wen-Chun

    2013-02-01

    Up-regulation of cyclooxygenase-2 (COX-2) is frequently found in human cancers and is significantly associated with tumor metastasis. Our previous results demonstrate that COX-2 and its metabolite prostaglandin E2 (PGE2) stimulate the expression of CCR7 chemokine receptor via EP2/EP4 receptors to promote lymphatic invasion in breast cancer cells. In this study, we address the underlying mechanism of COX-2/PGE2-induced CCR7 expression. We find that COX-2/PGE2 increase CCR7 expression via the AKT signaling pathway in breast cancer cells. Promoter deletion and mutation assays identify the Sp1 site located at the -60/-57 region of CCR7 gene promoter is critical for stimulation. Chromatin immunoprecipitation (ChIP) assay confirms that in vivo binding of Sp1 to human CCR7 promoter is increased by COX-2 and PGE2. Knockdown of Sp1 by shRNA reduces the induction of CCR7 by PGE2. We demonstrate for the first time that AKT may directly phosphorylate Sp1 at S42, T679, and S698. Phosphorylation-mimic Sp1 protein harboring S42D, T679D, and S698D mutation strongly activates CCR7 expression. In contrast, change of these three residues to alanine completely blocks the induction of CCR7 by PGE2. Pathological investigation demonstrates that CCR7 expression is strongly associated with phospho-AKT and Sp1 in 120 breast cancer tissues. Collectively, our results demonstrate that COX-2 up-regulates CCR7 expression via AKT-mediated phosphorylation and activation of Sp1 and this pathway is highly activated in metastatic breast cancer. Copyright © 2012 Wiley Periodicals, Inc.

  13. Multicenter trial validation of a camera-based method to measure Tc-99m mercaptoacetyltriglycine, or Tc-99m MAG3, clearance.

    Science.gov (United States)

    Taylor, A; Manatunga, A; Morton, K; Reese, L; Prato, F S; Greenberg, E; Folks, R; Kemp, B J; Jones, M E; Corrigan, P E; Galt, J; Eshima, L

    1997-07-01

    To evaluate an improved camera-based method for calculating the clearance of technetium-99m mercaptoacetyltriglycine (MAG3) in a multicenter trial. Tc-99m MAG3 scintigraphy was performed in 49 patients at three sites in the United States and Canada. The percentage of the injected dose of Tc-99m MAG3 in the kidney at 1-2, 1.0-2.5, and 2-3 minutes after injection was correlated with the plasma-based Tc-99m MAG3 clearances. The data were combined with the results obtained in 20 additional patients in a previously published pilot study. Regression models correlating the plasma-based Tc-99m MAG3 clearance with the percentage uptake in the kidney for each time interval were developed; there was no statistically significant difference among sites in the regression equations. Correction for body surface area statistically significantly (P time interval. For the 1.0-2.5-minute interval, the body surface area-corrected correlation coefficient for the four combined sites was .87, and it improved to .93 when one outlier was omitted from the analysis. Similar results were obtained with the other time intervals. Independent processing by two observers showed no clinically important differences in the percentage dose in the kidney or in relative function. An improved camera-based method to calculate the clearance of Tc-99m MAG3 was validated in a multicenter trial.

  14. Development and Application of an Indirect Enzyme-Linked Immunosorbent Assay Using Recombinant Mag1 for Serodiagnosis of Toxoplasma gondii In Dogs.

    Science.gov (United States)

    Zhuo, Xunhui; Sun, Hongchao; Zhang, Zhi; Luo, Jiaqing; Shan, Ying; Du, Aifang

    2017-06-01

    Serologic tests are widely accepted and applied as means to detect anti- Toxoplasma gondii immunoglobulin G antibodies. In this study, recombinant matrix antigen (rMAG1) was induced by isopropyl-β-d-thiogalactoside and purified by nickel-nitrilotriacetic acid purification system. We then developed and optimized an indirect enzyme-linked immunosorbent assay (ELISA) through checkerboard assays using serial dilutions of antigens and sera to assess the potential use of rMAG1 in serologic detection of T. gondii infection in dogs. Serum samples from 93 domestic dogs were analyzed by western blot and rMAG1-ELISA. The results were compared with those obtained from an ELISA with the soluble Toxoplasma lysate antigens (TLA). We found that although yielding an excellent agreement (96.7%) with western blot data (κ = 0.9659), rMAG1-ELISA produced higher sensitivity (93.9% vs. 87.8%) and specificity (98.3% vs. 96.7%) than TLA-ELISA. In addition, receiver operating characteristic analysis also revealed that rMAG1-ELISA is in more agreement with western blot (area under the curve [AUC] = 0.985) relative to TLA-ELISA (AUC = 0.955). These results indicated that the rMAG1-ELISA established in this study provides a promising and reliable tool for serologic detection of T. gondii infection in dogs.

  15. Upregulation of the Chemokine Receptor CCR7 expression by HIF-1αand HIF-2α in non-small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Yang LI

    2008-10-01

    Full Text Available Background and objective CCR7 is closely related with the lymph node metastasis of non-small cell lung cancer. The objective of this work is to investigate the expressions of chemokine receptor CCR7, hypoxiainducible factor 1α (HIF-1α and hypoxia inducible factor 2α (HIF-2α protein in non small cell lung cancer and the relationships of their expression, and to study the mechanism of CCR7 upregulation in NSCLC. Methods T he levels of expressions of CCR7, HIF-1α and HIF-2α protein were detected in 94 specimens of human primary non small cell lung cancer by immunohistochemical S-P method. Human lung adenocarcinoma cell line A549 cells were transfected by lipofection with HIF-1α siRNA、HIF-2α siRNA, the change of CCR7 was observed by RT-PCR and immunofluorescence staining. Correlations between the expression of CCR7 and HIF-1α, HIF-2α were respectively analyzed. Results Immunohistochemistry showed that CCR7 was distributed in cytoplasm and/or membrane of tumor cells, HIF-1α, HIF-2α was distributed in nucleus and/or cytoplasm of tumor cells. The levels of expressions of CCR7, HIF-1α and HIF-2α protein were found to be 75.53% (71/94, 54.25% (51/ 94 and 70.21% (66/94 in non small celllung cancer, respectively. the levels of expression of CCR7 protein were closely related to the clinical stages (P 0.05. Furthermore, A significant correlation were found among CCR7, Hif-1α and HIF-2α (r =0.272, P <0.01 (r=0.225, P <0.05. In addition, the expression of CCR7 mRNA and protein levels were decreased in the transfected specificHIF-1α, HIF-2αsiRNA group (P <0.05. Conclusion CCR7 expression is significantly associated with non small cell lung cancer invasion and metastasis. The upregulation of CCR7 is regulated by HIF-1α and HIF-2α in non small cell lung cancer.

  16. V-1 nuclear power plant standby RPP-16S computer software

    International Nuclear Information System (INIS)

    Suchy, R.

    1988-01-01

    The software structure of the function of program modules of the RPP-16S standby computer which is part of the information system of the V-1 Bohunice nuclear power plant are described. The multitasking AMOS operational system is used for the organization of programs in the computer. The program modules are classified in five groups by function, i.e., in modules for the periodical collection of values and for the measurement of process quantities for both nuclear power plant units; for the primary processing of the values; for the monitoring of exceedance of preset limits; for unit operators' communication with the computer. The fifth group consists of users program modules. The standby computer software was tested in the actual operating conditions of the V-1 power plant. The results showed it operated correctly; minor shortcomings were removed. (Z.M.). 1 fig

  17. Is decommissioning of the NPP V-1 in the years 2006/2008 justified?

    International Nuclear Information System (INIS)

    Hudcovsky, S.; Dvorak, K.

    2001-01-01

    The article asks for very detailed safety and technical analysis, making assessments of political reasons. It would be reasonable to prepare arguments for change of present governmental decision, which is still valid. Political decision is for a politician. Main lifetime of nuclear powe plant depends on pressurized reactor vessel. One of the big problem is reactor vessel embrittlement and this article provides the information on annealing which was already done and this problem has been solved at reasonable costs. Forecast for fatigue of reactor vessel for year 2010 is just 15%. Technical condition of V-1 NPP in 2010 will be not worse compared with first years of operation. There are no technical obstacles to stop the operation of V-1 NPP. (authors)

  18. Three-dimensional Force and Kinematic Interactions in V1 Skating at High Speeds.

    Science.gov (United States)

    Stöggl, Thomas; Holmberg, Hans-Christer

    2015-06-01

    To describe the detailed kinetics and kinematics associated with use of the V1 skating technique at high skiing speeds and to identify factors that predict performance. Fifteen elite male cross-country skiers performed an incremental roller-skiing speed test (Vpeak) on a treadmill using the V1 skating technique. Pole and plantar forces and whole-body kinematics were monitored at four submaximal speeds. The propulsive force of the "strong side" pole was greater than that of the "weak side" (P skating at high speeds. The faster skiers exhibit more symmetric leg motion on the "strong" and "weak" sides, as well as more synchronized poling. With respect to methods, the pressure insoles and three-dimensional kinematics in combination with the leg push-off model described here can easily be applied to all skating techniques, aiding in the evaluation of skiing techniques and comparison of effectiveness.

  19. Explosive Model Tarantula V1/JWL++ Calibration of LX-17: #2

    Energy Technology Data Exchange (ETDEWEB)

    Souers, P C; Vitello, P

    2009-05-01

    Tarantula V1 is a kinetic package for reactive flow codes that seeks to describe initiation, failure, dead zones and detonation simultaneously. The most important parameter is P1, the pressure between the initiation and failure regions. Both dead zone formation and failure can be largely controlled with this knob. However, V1 does failure with low settings and dead zones with higher settings, so that it cannot fulfill its purpose in the current format. To this end, V2 is under test. The derivation of the initiation threshold P0 is discussed. The derivation of the initiation pressure-tau curve as an output of Tarantula shows that the initiation package is sound. A desensitization package is also considered.

  20. Electronic, optical, and thermoelectric properties of Fe2+xV1−xAl

    Directory of Open Access Journals (Sweden)

    D. P. Rai

    2017-04-01

    Full Text Available We report the electronic, optical, and thermoelectric properties of full-Heusler alloy Fe2VAl with Fe antisite doping (Fe2+xV1−xAl as obtained from the first-principles Tran-Blaha modified Becke-Johnson potential. The results are discussed in relation to the available experimental data and show good agreements for the band gap, magnetic moment, and optical spectra. Exploring our transport data for thermoelectric applicability suggest that Fe2+xV1−xAl is a good candidate with a high figure of merit (ZT 0.75(0.65 for x = 0.25(0.50 at room temperature.

  1. MREG V1.1 : a multi-scale image registration algorithm for SAR applications.

    Energy Technology Data Exchange (ETDEWEB)

    Eichel, Paul H.

    2013-08-01

    MREG V1.1 is the sixth generation SAR image registration algorithm developed by the Signal Processing&Technology Department for Synthetic Aperture Radar applications. Like its predecessor algorithm REGI, it employs a powerful iterative multi-scale paradigm to achieve the competing goals of sub-pixel registration accuracy and the ability to handle large initial offsets. Since it is not model based, it allows for high fidelity tracking of spatially varying terrain-induced misregistration. Since it does not rely on image domain phase, it is equally adept at coherent and noncoherent image registration. This document provides a brief history of the registration processors developed by Dept. 5962 leading up to MREG V1.1, a full description of the signal processing steps involved in the algorithm, and a user's manual with application specific recommendations for CCD, TwoColor MultiView, and SAR stereoscopy.

  2. Analysis of the CCR5 gene coding region diversity in five South American populations reveals two new non-synonymous alleles in Amerindians and high CCR5*D32 frequency in Euro-Brazilians

    Directory of Open Access Journals (Sweden)

    Angelica B.W. Boldt

    2009-01-01

    Full Text Available The CC chemokine receptor 5 (CCR5 molecule is an important co-receptor for HIV. The effect of the CCR5*D32 allele in susceptibility to HIV infection and AIDS disease is well known. Other alleles than CCR5*D32 have not been analysed before, neither in Amerindians nor in the majority of the populations all over the world. We investigated the distribution of the CCR5 coding region alleles in South Brazil and noticed a high CCR5*D32 frequency in the Euro-Brazilian population of the Paraná State (9.3%, which is the highest thus far reported for Latin America. The D32 frequency is even higher among the Euro-Brazilian Mennonites (14.2%. This allele is uncommon in Afro-Brazilians (2.0%, rare in the Guarani Amerindians (0.4% and absent in the Kaingang Amerindians and the Oriental-Brazilians. R223Q is common in the Oriental-Brazilians (7.7% and R60S in the Afro-Brazilians (5.0%. A29S and L55Q present an impaired response to b-chemokines and occurred in Afro- and Euro-Brazilians with cumulative frequencies of 4.4% and 2.7%, respectively. Two new non-synonymous alleles were found in Amerindians: C323F (g.3729G > T in Guarani (1.4% and Y68C (g.2964A > G in Kaingang (10.3%. The functional characteristics of these alleles should be defined and considered in epidemiological investigations about HIV-1 infection and AIDS incidence in Amerindian populations.

  3. Leukocyte attraction by CCL20 and its receptor CCR6 in humans and mice with pneumococcal meningitis

    NARCIS (Netherlands)

    Klein, Matthias; Brouwer, Matthijs C.; Angele, Barbara; Geldhoff, Madelijn; Marquez, Gabriel; Varona, Rosa; Häcker, Georg; Schmetzer, Helga; Häcker, Hans; Hammerschmidt, Sven; van der Ende, Arie; Pfister, Hans-Walter; van de Beek, Diederik; Koedel, Uwe

    2014-01-01

    We previously identified CCL20 as an early chemokine in the cerebrospinal fluid (CSF) of patients with pneumococcal meningitis but its functional relevance was unknown. Here we studied the role of CCL20 and its receptor CCR6 in pneumococcal meningitis. In a prospective nationwide study, CCL20 levels

  4. CCR1, an enzyme required for lignin biosynthesis in Arabidopsis, mediates cell proliferation exit for leaf development

    DEFF Research Database (Denmark)

    Xue, Jingshi; Luo, Dexian; Xu, Deyang

    2015-01-01

    A level was dramatically reduced. Cell proliferation in comt ccoaomt leaves was decreased, accompanied by elevated ROS levels, and the mutant phenotypes were partially rescued by treatment with FeA or another antioxidant (N-acetyl-L-cysteine). Taken together, our results suggest that CCR1, FeA and ROS...

  5. Effects of sequence changes in the HIV-1 gp41 fusion peptide on CCR5 inhibitor resistance

    International Nuclear Information System (INIS)

    Anastassopoulou, Cleo G.; Ketas, Thomas J.; Sanders, Rogier W.; Johan Klasse, Per; Moore, John P.

    2012-01-01

    A rare pathway of HIV-1 resistance to small molecule CCR5 inhibitors such as Vicriviroc (VCV) involves changes solely in the gp41 fusion peptide (FP). Here, we show that the G516V change is critical to VCV resistance in PBMC and TZM-bl cells, although it must be accompanied by either M518V or F519I to have a substantial impact. Modeling VCV inhibition data from the two cell types indicated that G516V allows both double mutants to use VCV-CCR5 complexes for entry. The model further identified F519I as an independent determinant of preference for the unoccupied, high-VCV affinity form of CCR5. From inhibitor-free reversion cultures, we also identified a substitution in the inner domain of gp120, T244A, which appears to counter the resistance phenotype created by the FP substitutions. Examining the interplay of these changes will enhance our understanding of Env complex interactions that influence both HIV-1 entry and resistance to CCR5 inhibitors.

  6. A Linear Epitope in the N-Terminal Domain of CCR5 and Its Interaction with Antibody.

    Directory of Open Access Journals (Sweden)

    Benny Chain

    Full Text Available The CCR5 receptor plays a role in several key physiological and pathological processes and is an important therapeutic target. Inhibition of the CCR5 axis by passive or active immunisation offers one very selective strategy for intervention. In this study we define a new linear epitope within the extracellular domain of CCR5 recognised by two independently produced monoclonal antibodies. A short peptide encoding the linear epitope can induce antibodies which recognise the intact receptor when administered colinear with a tetanus toxoid helper T cell epitope. The monoclonal antibody RoAb 13 is shown to bind to both cells and peptide with moderate to high affinity (6x10^8 and 1.2x107 M-1 respectively, and binding to the peptide is enhanced by sulfation of tyrosines at positions 10 and 14. RoAb13, which has previously been shown to block HIV infection, also blocks migration of monocytes in response to CCR5 binding chemokines and to inflammatory macrophage conditioned medium. A Fab fragment of RoAb13 has been crystallised and a structure of the antibody is reported to 2.1 angstrom resolution.

  7. OSCAR Is a Receptor for Surfactant Protein D That Activates TNF-α Release from Human CCR2+ Inflammatory Monocytes

    DEFF Research Database (Denmark)

    Barrow, Alexander D; Palarasah, Yaseelan; Bugatti, Mattia

    2015-01-01

    of recombinant SP-D and captured native SP-D from human bronchoalveolar lavage. OSCAR localized in an intracellular compartment of alveolar macrophages together with SP-D. Moreover, we found OSCAR on the surface of interstitial lung and blood CCR2(+) inflammatory monocytes, which secreted TNF-α when exposed...

  8. Differential between Protein and mRNA Expression of CCR7 and SSTR5 Receptors in Crohn's Disease Patients

    Directory of Open Access Journals (Sweden)

    Nathalie Taquet

    2009-01-01

    Full Text Available Crohn's disease (CD is a multifactorial chronic inflammatory bowel disease of unknown cause. The aim of the present study was to explore if mRNA over-expression of SSTR5 and CCR7 found in CD patients could be correlated to respective protein expression. When compared to healthy donors, SSTR5 was over-expressed 417 ± 71 times in CD peripheral blood mononuclear cells (PBMCs. Flow cytometry experiments showed no correlation between mRNA and protein expression for SSTR5 in PBMCs. In an attempt to find a reason of such a high mRNA expression, SSTR5 present on CD PBMCs were tested and found as biologically active as on healthy cells. In biopsies of CD intestinal tissue, SSTR5 was not over-expressed but CCR7, unchanged in PBMCs, was over-expressed by 10 ± 3 times in the lamina propria. Confocal microscopy showed a good correlation of CCR7 mRNA and protein expression in CD intestinal biopsies. Our data emphasize flow and image cytometry as impossible to circumvent in complement to molecular biology so to avoid false interpretation on receptor expressions. Once confirmed by further large-scale studies, our preliminary results suggest a role for SSTR5 and CCR7 in CD pathogenesis.

  9. Interaction between NANOS2 and the CCR4-NOT deadenylation complex is essential for male germ cell development in mouse.

    Directory of Open Access Journals (Sweden)

    Atsushi Suzuki

    Full Text Available Nanos is one of the evolutionarily conserved proteins implicated in germ cell development and we have previously shown that it interacts with the CCR4-NOT deadenylation complex leading to the suppression of specific RNAs. However, the molecular mechanism and physiological significance of this interaction have remained elusive. In our present study, we identify CNOT1, a component of the CCR4-NOT deadenylation complex, as a direct factor mediating the interaction with NANOS2. We find that the first 10 amino acids (AAs of NANOS2 are required for this binding. We further observe that a NANOS2 mutant lacking these first 10 AAs (NANOS2-ΔN10 fails to rescue defects in the Nanos2-null mouse. Our current data thus indicate that the interaction with the CCR4-NOT deadenylation complex is essential for NANOS2 function. In addition, we further demonstrate that NANOS2-ΔN10 can associate with specific mRNAs as well as wild-type NANOS2, suggesting the existence of other NANOS2-associated factor(s that determine the specificity of RNA-binding independently of the CCR4-NOT deadenylation complex.

  10. Upgrading of the radiation protection system at the V1 NPP

    International Nuclear Information System (INIS)

    Dobis, L.; Kaizer, J.; Svitek, J.

    2003-01-01

    The original radiation protection system at Bohunice V1 NPP from the 1970s was upgraded so as to meet current national as well as international standards. The article describes the upgrading of the radiation control system (teledosimetry, emergency measurement in the hermetic zone, liquid discharges, gaseous discharges, service water, remote measurement, hygiene loop, contamination monitoring at the controlled zone exit and activity monitoring at the NPP exit, special laundry, instrument calibration), dosimetry, software, and personnel contamination inspection/measurement. (author)

  11. Seismic strengthening of nuclear power plants V1-V2 structures in Slovak Republic

    International Nuclear Information System (INIS)

    David, M.

    1993-01-01

    The structural upgrading of main buildings of Bohunice NPP units V1 and V2 is described in this presentation. Design criteria for structural upgrading are included. Since the seismic upgrading of the existing NPP is usually very complicated and expensive task, designer is obliged to find the optimal solution between the economics and reliability of the upgrading. The assistance of IAEA missions during the process of Bohunice seismic upgrading is considered very fruitful

  12. V1 spinal neurons regulate the speed of vertebrate locomotor outputs

    DEFF Research Database (Denmark)

    Gosgnach, Simon; Lanuza, Guillermo M.; Butt, Simon J B

    2006-01-01

    The neuronal networks that generate vertebrate movements such as walking and swimming are embedded in the spinal cord1-3. These networks, which are referred to as central pattern generators (CPGs), are ideal systems for determining how ensembles of neurons generate simple behavioural outputs...... for inhibition in regulating the frequency of the locomotor CPG rhythm, and also suggest that V1 neurons may have an evolutionarily conserved role in controlling the speed of vertebrate locomotor movements....

  13. Recurrent connectivity can account for the dynamics of disparity processing in V1

    Science.gov (United States)

    Samonds, Jason M.; Potetz, Brian R.; Tyler, Christopher W.; Lee, Tai Sing

    2013-01-01

    Disparity tuning measured in the primary visual cortex (V1) is described well by the disparity energy model, but not all aspects of disparity tuning are fully explained by the model. Such deviations from the disparity energy model provide us with insight into how network interactions may play a role in disparity processing and help to solve the stereo correspondence problem. Here, we propose a neuronal circuit model with recurrent connections that provides a simple account of the observed deviations. The model is based on recurrent connections inferred from neurophysiological observations on spike timing correlations, and is in good accord with existing data on disparity tuning dynamics. We further performed two additional experiments to test predictions of the model. First, we increased the size of stimuli to drive more neurons and provide a stronger recurrent input. Our model predicted sharper disparity tuning for larger stimuli. Second, we displayed anti-correlated stereograms, where dots of opposite luminance polarity are matched between the left- and right-eye images and result in inverted disparity tuning in the disparity energy model. In this case, our model predicted reduced sharpening and strength of inverted disparity tuning. For both experiments, the dynamics of disparity tuning observed from the neurophysiological recordings in macaque V1 matched model simulation predictions. Overall, the results of this study support the notion that, while the disparity energy model provides a primary account of disparity tuning in V1 neurons, neural disparity processing in V1 neurons is refined by recurrent interactions among elements in the neural circuit. PMID:23407952

  14. A 'variable' stellar object in a variable blue nebula V-V 1-7

    International Nuclear Information System (INIS)

    Rao, N.K.; Gilra, D.P.

    1981-01-01

    V-V 1-7 is supposed to be one of the few planetary nebulae with Ao central stars and was included in the planetary-nebula catalogue as PK 235 + 1 0 1. The nebula was seen on the blue Palomar Observatory Sky Survey (POSS) print but not on the red print; as a result it was thought that it might be a reflection nebula. However, the symmetry of the nebula around the central star (HD 62001), and also the ultraviolet photometric variability of this central star led others to suggest that the nebula might be a nova shell. Subsequently it was found that the nebula V-V 1-7 has disappeared. It is not seen on any direct plate known to us except the POSS blue plate. In this paper the disappearance is reported (along with the nebula) of a stellar object, which appears within the 'nebular shell' of V-V 1-7 on the POSS blue plate, but not on the red plate. (author)

  15. Spatial Attention and Temporal Expectation Under Timed Uncertainty Predictably Modulate Neuronal Responses in Monkey V1

    Science.gov (United States)

    Sharma, Jitendra; Sugihara, Hiroki; Katz, Yarden; Schummers, James; Tenenbaum, Joshua; Sur, Mriganka

    2015-01-01

    The brain uses attention and expectation as flexible devices for optimizing behavioral responses associated with expected but unpredictably timed events. The neural bases of attention and expectation are thought to engage higher cognitive loci; however, their influence at the level of primary visual cortex (V1) remains unknown. Here, we asked whether single-neuron responses in monkey V1 were influenced by an attention task of unpredictable duration. Monkeys covertly attended to a spot that remained unchanged for a fixed period and then abruptly disappeared at variable times, prompting a lever release for reward. We show that monkeys responded progressively faster and performed better as the trial duration increased. Neural responses also followed monkey's task engagement—there was an early, but short duration, response facilitation, followed by a late but sustained increase during the time monkeys expected the attention spot to disappear. This late attentional modulation was significantly and negatively correlated with the reaction time and was well explained by a modified hazard function. Such bimodal, time-dependent changes were, however, absent in a task that did not require explicit attentional engagement. Thus, V1 neurons carry reliable signals of attention and temporal expectation that correlate with predictable influences on monkeys' behavioral responses. PMID:24836689

  16. Development and matching of binocular orientation preference in mouse V1.

    Science.gov (United States)

    Bhaumik, Basabi; Shah, Nishal P

    2014-01-01

    Eye-specific thalamic inputs converge in the primary visual cortex (V1) and form the basis of binocular vision. For normal binocular perceptions, such as depth and stereopsis, binocularly matched orientation preference between the two eyes is required. A critical period of binocular matching of orientation preference in mice during normal development is reported in literature. Using a reaction diffusion model we present the development of RF and orientation selectivity in mouse V1 and investigate the binocular orientation preference matching during the critical period. At the onset of the critical period the preferred orientations of the modeled cells are mostly mismatched in the two eyes and the mismatch decreases and reaches levels reported in juvenile mouse by the end of the critical period. At the end of critical period 39% of cells in binocular zone in our model cortex is orientation selective. In literature around 40% cortical cells are reported as orientation selective in mouse V1. The starting and the closing time for critical period determine the orientation preference alignment between the two eyes and orientation tuning in cortical cells. The absence of near neighbor interaction among cortical cells during the development of thalamo-cortical wiring causes a salt and pepper organization in the orientation preference map in mice. It also results in much lower % of orientation selective cells in mice as compared to ferrets and cats having organized orientation maps with pinwheels.

  17. Development and Matching of Binocular Orientation Preference in Mouse V1

    Directory of Open Access Journals (Sweden)

    Basabi eBhaumik

    2014-07-01

    Full Text Available Eye-specific thalamic inputs converge in the primary visual cortex (V1 and form the basis of binocular vision. For normal binocular perceptions, such as depth and stereopsis, binocularly matched orientation preference between the two eyes is required. A critical period of binocular matching of orientation preference in mice during normal development is reported in literature. Using a reaction diffusion model we present the development of RF and orientation selectivity in mouse V1 and investigate the binocular orientation preference matching during the critical period. At the onset of the critical period the preferred orientations of the modeled cells are mostly mismatched in the two eyes and the mismatch decreases and reaches levels reported in juvenile mouse by the end of the critical period. At the end of critical period 39% of cells in binocular zone in our model cortex is orientation selective. In literature around 40% cortical cells are reported as orientation selective in mouse V1. The starting and the closing time for critical period determine the orientation preference alignment between the two eyes and orientation tuning in cortical cells. The absence of near neighbor interaction among cortical cells during the development of thalmo-cortical wiring causes a salt and pepper organization in the orientation preference map in mice. It also results in much lower % of orientation selective cells in mice as compared to ferrets and cats having organized orientation maps with pinwheels.

  18. Revealing Detail along the Visual Hierarchy: Neural Clustering Preserves Acuity from V1 to V4.

    Science.gov (United States)

    Lu, Yiliang; Yin, Jiapeng; Chen, Zheyuan; Gong, Hongliang; Liu, Ye; Qian, Liling; Li, Xiaohong; Liu, Rui; Andolina, Ian Max; Wang, Wei

    2018-04-18

    How primates perceive objects along with their detailed features remains a mystery. This ability to make fine visual discriminations depends upon a high-acuity analysis of spatial frequency (SF) along the visual hierarchy from V1 to inferotemporal cortex. By studying the transformation of SF across macaque parafoveal V1, V2, and V4, we discovered SF-selective functional domains in V4 encoding higher SFs up to 12 cycles/°. These intermittent higher-SF-selective domains, surrounded by domains encoding lower SFs, violate the inverse relationship between SF preference and retinal eccentricity. The neural activities of higher- and lower-SF domains correspond to local and global features, respectively, of the same stimuli. Neural response latencies in high-SF domains are around 10 ms later than in low-SF domains, consistent with the coarse-to-fine nature of perception. Thus, our finding of preserved resolution from V1 into V4, separated both spatially and temporally, may serve as a connecting link for detailed object representation. Copyright © 2018 Elsevier Inc. All rights reserved.

  19. Contextual modulation revealed by optical imaging exhibits figural asymmetry in macaque V1 and V2.

    Science.gov (United States)

    Zarella, Mark D; Ts'o, Daniel Y

    2017-01-01

    Neurons in early visual cortical areas are influenced by stimuli presented well beyond the confines of their classical receptive fields, endowing them with the ability to encode fine-scale features while also having access to the global context of the visual scene. This property can potentially define a role for the early visual cortex to contribute to a number of important visual functions, such as surface segmentation and figure-ground segregation. It is unknown how extraclassical response properties conform to the functional architecture of the visual cortex, given the high degree of functional specialization in areas V1 and V2. We examined the spatial relationships of contextual activations in macaque V1 and V2 with intrinsic signal optical imaging. Using figure-ground stimulus configurations defined by orientation or motion, we found that extraclassical modulation is restricted to the cortical representations of the figural component of the stimulus. These modulations were positive in sign, suggesting a relative enhancement in neuronal activity that may reflect an excitatory influence. Orientation and motion cues produced similar patterns of activation that traversed the functional subdivisions of V2. The asymmetrical nature of the enhancement demonstrated the capacity for visual cortical areas as early as V1 to contribute to figure-ground segregation, and the results suggest that this information can be extracted from the population activity constrained only by retinotopy, and not the underlying functional organization.

  20. Cortical depth dependent population receptive field attraction by spatial attention in human V1.

    Science.gov (United States)

    Klein, Barrie P; Fracasso, Alessio; van Dijk, Jelle A; Paffen, Chris L E; Te Pas, Susan F; Dumoulin, Serge O

    2018-04-27

    Visual spatial attention concentrates neural resources at the attended location. Recently, we demonstrated that voluntary spatial attention attracts population receptive fields (pRFs) toward its location throughout the visual hierarchy. Theoretically, both a feed forward or feedback mechanism could underlie pRF attraction in a given cortical area. Here, we use sub-millimeter ultra-high field functional MRI to measure pRF attraction across cortical depth and assess the contribution of feed forward and feedback signals to pRF attraction. In line with previous findings, we find consistent attraction of pRFs with voluntary spatial attention in V1. When assessed as a function of cortical depth, we find pRF attraction in every cortical portion (deep, center and superficial), although the attraction is strongest in deep cortical portions (near the gray-white matter boundary). Following the organization of feed forward and feedback processing across V1, we speculate that a mixture of feed forward and feedback processing underlies pRF attraction in V1. Specifically, we propose that feedback processing contributes to the pRF attraction in deep cortical portions. Copyright © 2018. Published by Elsevier Inc.

  1. Analysis of events significant with regard to safety of Bohunice V-1 nuclear power plant

    International Nuclear Information System (INIS)

    Suchomel, J.; Maron, V.; Kmosena, J.

    1986-01-01

    An analysis was made of operating safety of the V-1 nuclear power plant in Jaslovske Bohunice for the years 1980 - 1983. Of the total number of 676 reported failures only three were events with special safety significance, namely a complete loss of power supply for own consumption from the power grid, a failure of pins on the collectors of steam generators, and a failure of the heads of heat technology inspection channels. The failures were categorized according to the systems used in the USSR and in the USA and compared with data on failures in nuclear power plants in the two countries. The conclusions show that the operation of the V-1 nuclear power plant achieves results which are fully comparable with those recorded in 9 WWER-440 power plants operating in various countries. The average coefficient of availability is 0.72 and ranks the power plant in the fourth place among the said 9 plants. A comparison of the individual power plant units showed that of the total number of 22, the first unit of the V-1 plant ranks fifth with a coefficient of 0.78 and the second unit with a coefficient of 0.69 ranks 15th. (Z.M.)

  2. SModelS v1.1 user manual: Improving simplified model constraints with efficiency maps

    Science.gov (United States)

    Ambrogi, Federico; Kraml, Sabine; Kulkarni, Suchita; Laa, Ursula; Lessa, Andre; Magerl, Veronika; Sonneveld, Jory; Traub, Michael; Waltenberger, Wolfgang

    2018-06-01

    SModelS is an automatized tool for the interpretation of simplified model results from the LHC. It allows to decompose models of new physics obeying a Z2 symmetry into simplified model components, and to compare these against a large database of experimental results. The first release of SModelS, v1.0, used only cross section upper limit maps provided by the experimental collaborations. In this new release, v1.1, we extend the functionality of SModelS to efficiency maps. This increases the constraining power of the software, as efficiency maps allow to combine contributions to the same signal region from different simplified models. Other new features of version 1.1 include likelihood and χ2 calculations, extended information on the topology coverage, an extended database of experimental results as well as major speed upgrades for both the code and the database. We describe in detail the concepts and procedures used in SModelS v1.1, explaining in particular how upper limits and efficiency map results are dealt with in parallel. Detailed instructions for code usage are also provided.

  3. Purification and characterization of the V1 vasopressin receptor from rat liver

    International Nuclear Information System (INIS)

    Fishman, J.B.; Dickey, B.F.; Attisano, C.; Fine, R.E.

    1987-01-01

    The rat liver V1 vasopressin receptor was purified approximately 21,000-fold from rat liver microsomes. The receptor was solubilized from membranes using the zwitterionic detergent CHAPS (3-[(3-cholamidopropyl) dimethylammonio]-1-propanesulfonate). Since the V1 receptor loses its ability to bind ligand when solubilized, the authors devised a liposome reconstitution system to assay vasopressin binding activity during purification. The purified receptor exhibits a K/sub d/ of 6 nm, when, prior to solubilization, the membranes were exposed to 1 μm vasopressin. This resulted in the association of a pertussis-toxin insensitive guanine-nucleotide binding protein with the receptor during most of the purification procedure. The authors are further characterizing the V1-associated G-proteins. In the absence of this association, the receptor has a K/sub d/ of 30 nM. Crosslinking of 125 I-vasopressin to a partially purified preparation of receptor demonstrated that the receptor had a molecular weight of approximately 68,000 under reducing conditions, and 58,000 under non-reducing conditions. The purification procedure may prove useful in purifying a number of small peptide hormone receptors (e.g., bradykinin, angiotensin II) and perhaps their associated G-proteins as well

  4. METEOR v1.0 - Design and structure of the software package

    International Nuclear Information System (INIS)

    Palomo, E.

    1994-01-01

    This script describes the structure and the separated modules of the software package METEOR for the statistical analysis of meteorological data series. It contains a systematic description of the subroutines of METEOR and, also, of the required shape for input and output files. The original version of METEOR have been developed by Ph.D. Elena Palomo, CIEMAT-IER, GIMASE. It is built by linking programs and routines written in FORTRAN 77 and it adds thc graphical capabilities of GNUPLOT. The shape of this toolbox was designed following the criteria of modularity, flexibility and agility criteria. All the input, output and analysis options are structured in three main menus: i) the first is aimed to evaluate the quality of the data set; ii) the second is aimed for pre-processing of the data; and iii) the third is aimed towards the statistical analyses and for creating the graphical outputs. Actually the information about METEOR is constituted by three documents written in spanish: 1) METEOR v1.0: User's guide; 2) METEOR v1.0: A usage example; 3) METEOR v 1.0: Design and structure of the software package. (Author)

  5. In vitro binding and receptor-mediated activity of terlipressin at vasopressin receptors V1 and V2.

    Science.gov (United States)

    Jamil, Khurram; Pappas, Stephen Chris; Devarakonda, Krishna R

    2018-01-01

    Terlipressin, a synthetic, systemic vasoconstrictor with selective activity at vasopressin-1 (V 1 ) receptors, is a pro-drug for the endogenous/natural porcine hormone [Lys 8 ]-vasopressin (LVP). We investigated binding and receptor-mediated cellular activities of terlipressin, LVP, and endogenous human hormone [Arg 8 ]-vasopressin (AVP) at V 1 and vasopressin-2 (V 2 ) receptors. Cell membrane homogenates of Chinese hamster ovary cells expressing human V 1 and V 2 receptors were used in competitive binding assays to measure receptor-binding activity. These cells were used in functional assays to measure receptor-mediated cellular activity of terlipressin, LVP, and AVP. Binding was measured by [ 3 H]AVP counts, and the activity was measured by fluorometric detection of intracellular calcium mobilization (V 1 ) and cyclic adenosine monophosphate (V 2 ). Binding potency at V 1 and V 2 was AVP>LVP>terlipressin. LVP and terlipressin had approximately sixfold higher affinity for V 1 than for V 2 . Cellular activity potency was also AVP>LVP>terlipressin. Terlipressin was a partial agonist at V 1 and a full agonist at V 2 ; LVP was a full agonist at both V 1 and V 2 . The in vivo response to terlipressin is likely due to the partial V 1 agonist activity of terlipressin and full V 1 agonist activity of its metabolite, LVP. These results provide supportive evidence for previous findings and further establish terlipressin pharmacology for vasopressin receptors.

  6. Transmitted/founder and chronic subtype C HIV-1 use CD4 and CCR5 receptors with equal efficiency and are not inhibited by blocking the integrin α4β7.

    Directory of Open Access Journals (Sweden)

    Nicholas F Parrish

    Full Text Available Sexual transmission of human immunodeficiency virus type 1 (HIV-1 most often results from productive infection by a single transmitted/founder (T/F virus, indicating a stringent mucosal bottleneck. Understanding the viral traits that overcome this bottleneck could have important implications for HIV-1 vaccine design and other prevention strategies. Most T/F viruses use CCR5 to infect target cells and some encode envelope glycoproteins (Envs that contain fewer potential N-linked glycosylation sites and shorter V1/V2 variable loops than Envs from chronic viruses. Moreover, it has been reported that the gp120 subunits of certain transmitted Envs bind to the gut-homing integrin α4β7, possibly enhancing virus entry and cell-to-cell spread. Here we sought to determine whether subtype C T/F viruses, which are responsible for the majority of new HIV-1 infections worldwide, share biological properties that increase their transmission fitness, including preferential α4β7 engagement. Using single genome amplification, we generated panels of both T/F (n = 20 and chronic (n = 20 Env constructs as well as full-length T/F (n = 6 and chronic (n = 4 infectious molecular clones (IMCs. We found that T/F and chronic control Envs were indistinguishable in the efficiency with which they used CD4 and CCR5. Both groups of Envs also exhibited the same CD4+ T cell subset tropism and showed similar sensitivity to neutralization by CD4 binding site (CD4bs antibodies. Finally, saturating concentrations of anti-α4β7 antibodies failed to inhibit infection and replication of T/F as well as chronic control viruses, although the growth of the tissue culture-adapted strain SF162 was modestly impaired. These results indicate that the population bottleneck associated with mucosal HIV-1 acquisition is not due to the selection of T/F viruses that use α4β7, CD4 or CCR5 more efficiently.

  7. Identification of four families of yCCR4- and Mg2+-dependent endonuclease-related proteins in higher eukaryotes, and characterization of orthologs of yCCR4 with a conserved leucine-rich repeat essential for hCAF1/hPOP2 binding

    Directory of Open Access Journals (Sweden)

    Corbo Laura

    2001-11-01

    Full Text Available Abstract Background The yeast yCCR4 factor belongs to the CCR4-NOT transcriptional regulatory complex, in which it interacts, through its leucine-rich repeat (LRR motif with yPOP2. Recently, yCCR4 was shown to be a component of the major cytoplasmic mRNA deadenylase complex, and to contain a fold related to the Mg2+-dependent endonuclease core. Results Here, we report the identification of nineteen yCCR4-related proteins in eukaryotes (including yeast, plants and animals, which all contain the yCCR4 endonuclease-like fold, with highly conserved CCR4-specific residues. Phylogenetic and genomic analyses show that they form four distinct families, one of which contains the yCCR4 orthologs. The orthologs in animals possess a leucine-rich repeat domain. We show, using two-hybrid and far-Western assays, that the human member binds to the human yPOP2 homologs, i.e. hCAF1 and hPOP2, in a LRR-dependent manner. Conclusions We have identified the mammalian orthologs of yCCR4 and have shown that the human member binds to the human yPOP2 homologs, thus strongly suggesting conservation of the CCR4-NOT complex from yeast to human. All members of the four identified yCCR4-related protein families show stricking conservation of the endonuclease-like catalytic motifs of the yCCR4 C-terminal domain and therefore constitute a new family of potential deadenylases in mammals.

  8. Improved the accuracy of 99mTc-MAG3 plasma clearance method. The problem of the calculated plasma volume and its modification

    International Nuclear Information System (INIS)

    Watanabe, Nami; Komatani, Akio; Yamaguchi, Koichi; Takahashi, Kazuei

    1998-01-01

    The 99m Tc-MAG 3 plasma clearance method (MPC method), reported by Oriuchi et al., is a simple and useful count-based gamma camera method for calculating the 99m Tc-MAG 3 plasma clearance (CL MAG ). However, a discrepancy of CL MAG calculated by MPC method (MPC-CL MAG ) from the tubular extraction rate (TER) calculated by Russell's single-sample clearance determination (Russell-TER) was noted. The calculated plasma volume is assumed to be the cause. Since the plasma volume is reported to have a linear correlation with body surface area, Dissmann's formula was applied to calculate the plasma volume. Then Dissmann's formula was replaced by Ogawa's formula in the MPC method, and the procedure was then called the modified MPC method. The CL MAG were obtained using MPC method, modified MPC method and the TER was obtained Russell's method in 95 patients with urological disorders. Then the MPC-CL MAG and modified MPC-CL MAG were compared with Russell-TER. Comparison of the MPC-CL MAG with the Russell-TER demonstrated a coefficient of correlation of 0.82, but dissociation of the slope of regression lines was found between males and females. The modified MPC-CL MAG improved the coefficient of correlation to 0.92, and diminished the dissociation of the slope of regression lines between males and females. We verified that the dissociation was due to the plasma volume calculated by Ogawa's formula. Ogawa's formula included hematocrit, body weight, body height and different coefficients for gender. The plasma volume calculated by Ogawa's formula were lower in males and higher in females than that calculated by Dissmann's formula. And marked discrepancy in the plasma volume in patients with a body surface area below 0.5 m 2 was observed. So the MPC method might become more accurate by substituting Dissmann's formula for Ogawa's formula resoluting in a method that is applicable to both males and females, children and adults in clinical use. (author)

  9. Managing Rock and Paleomagnetic Data Flow with the MagIC Database: from Measurement and Analysis to Comprehensive Archive and Visualization

    Science.gov (United States)

    Koppers, A. A.; Minnett, R. C.; Tauxe, L.; Constable, C.; Donadini, F.

    2008-12-01

    The Magnetics Information Consortium (MagIC) is commissioned to implement and maintain an online portal to a relational database populated by rock and paleomagnetic data. The goal of MagIC is to archive all measurements and derived properties for studies of paleomagnetic directions (inclination, declination) and intensities, and for rock magnetic experiments (hysteresis, remanence, susceptibility, anisotropy). Organizing data for presentation in peer-reviewed publications or for ingestion into databases is a time-consuming task, and to facilitate these activities, three tightly integrated tools have been developed: MagIC-PY, the MagIC Console Software, and the MagIC Online Database. A suite of Python scripts is available to help users port their data into the MagIC data format. They allow the user to add important metadata, perform basic interpretations, and average results at the specimen, sample and site levels. These scripts have been validated for use as Open Source software under the UNIX, Linux, PC and Macintosh© operating systems. We have also developed the MagIC Console Software program to assist in collating rock and paleomagnetic data for upload to the MagIC database. The program runs in Microsoft Excel© on both Macintosh© computers and PCs. It performs routine consistency checks on data entries, and assists users in preparing data for uploading into the online MagIC database. The MagIC website is hosted under EarthRef.org at http://earthref.org/MAGIC/ and has two search nodes, one for paleomagnetism and one for rock magnetism. Both nodes provide query building based on location, reference, methods applied, material type and geological age, as well as a visual FlashMap interface to browse and select locations. Users can also browse the database by data type (inclination, intensity, VGP, hysteresis, susceptibility) or by data compilation to view all contributions associated with previous databases, such as PINT, GMPDB or TAFI or other user

  10. Characterization of the virus-cell interactions by HIV-1 subtype C variants from an antiretroviral therapy-naïve subject with baseline resistance to the CCR5 inhibitor maraviroc

    DEFF Research Database (Denmark)

    Jakobsen, Martin Roelsgaard

    The CCR5 inhibitor maraviroc (MVC) exerts its antiviral activity by binding to- and altering the conformation of the CCR5 extracellular loops such that HIV-1 gp120 no longer recognizes CCR5. Viruses that have become resistant to MVC through long-term in vitro culture, or from treatment failure...... in vivo, can use the MVCbound form of CCR5 for HIV-1 entry via adaptive alterations in gp120. Partial baseline resistance to another CCR5 inhibitor through this mechanism, AD101, has been noted recently in one subject (1). Here, we identified and characterized envelope (Env) clones with baseline...

  11. Radiological characterisation on V1 NPP technological systems and buildings - Contamination

    International Nuclear Information System (INIS)

    Hanzel, Richard; Rapant, Tibor; Svitek, Jaroslav

    2012-01-01

    Since 2001, the preparation of V1 NPP practical decommissioning has been supported and partly financed by the Bohunice International Decommissioning Support Fund, under the administration of the European bank for Reconstruction and development. AMEC Nuclear Slovakia, together with partners STM Power and EWN GmbH, performed BIDSF B.4 project - Decommissioning database development. The main purpose of the B6.4 project was to develop a comprehensive physical and radiological inventory database to support RAW management development of the decommissioning studies and decommissioning project of Bohunice V1 NPP. AMEC Nuclear Slovakia was responsible mainly for DDB design, planning documents and physical and radiological characterization including sampling and analyses of the plant controlled area. The objective of V1 NPP radiological characterization was summarisation of sampling and analyses results, description of methodology used for radiological characterization and determination of the V1 NPP radiological inventory. Results of the characterization survey included the identification and distribution of contamination in buildings, structures, and other site facilities or other impacted media. The characterization survey clearly identified those portions of the site that have been affected by site activities and are contaminated. The survey also identified the portions of the site that have not been affected by these activities and can be marked as 'not impacted'. Radiological data have been presented also on the basis of index RAI level, where 5 radiological classes have been defined. On the basis of sampling and analyses results following radiological parameters have been assigned to all impacted components and civil structures included in DDB: dose rate in contact, dose rate in distance 1 m, external surface contamination, internal surface contamination and volume/mass contamination. Each room in controlled area has been described by following radiological parameters

  12. Radiological characterisation of V1 NPP technological systems and buildings - Activation

    International Nuclear Information System (INIS)

    Kristofova, Kristina; Rapant, Tibor; Svitek, Jaroslav

    2012-01-01

    V1 NPP at Jaslovske Bohunice site has been finally shutdown after 28 years of successful operation in 2006 (Unit 1) and 2008 (Unit 2). At present, both units are finally shutdown and since July 2011 under decommissioning license. The preparation of V1 NPP decommissioning has been supported and partly financed by the Bohunice International Decommissioning Support Fund (BIDSF), under the administration of the European Bank for Reconstruction and Development. From 06/2008 to 12/2011 AMEC Nuclear Slovakia, together with partners STM Power and EWN GmbH, carried out BIDSF B6.4 project - Decommissioning database development (DDB). The main purpose of the B6.4 project was to develop a physical and radiological inventory database to support V1 NPP decommissioning process planning and performance. One of the specific deliverable tasks within the B6.4 project was deliverable D12 - Characterization of activated equipment and civil structures based on measurement, sampling and analyses performed on the samples. The scope of deliverable services within D12 task consisted of: 1. Categorization of activated components ; 2. Development of single working programs for their radiological monitoring and sampling ; 3. Preparation of sampling device and revision of all handling equipment; 4. Dose rate monitoring and sampling of: - Civil structures from reactors shaft on both units ; - Components placed in HLW storage, (so called 'Mogilnik') - connection rods, absorbers ; of control rod assemblies and neutron flux measurement channels ; - Reactor pressure vessel and shielding assemblies at both units of V1 NPP, reactor; internals from Unit 2 of V1 NPP; 5. Analysis of samples ; 6. Determination of radiological inventory ; 7. Import of radiological data for activated components into DDB. During sampling, mainly remotely controlled sampling device and radiation resistant camera with LED lightening for visual checking of all performed activities was used. In total, 125 samples have been taken

  13. Simvastatin Inhibits IL-5-Induced Chemotaxis and CCR3 Expression of HL-60-Derived and Human Primary Eosinophils.

    Science.gov (United States)

    Fu, Chia-Hsiang; Tsai, Wan-Chun; Lee, Ta-Jen; Huang, Chi-Che; Chang, Po-Hung; Su Pang, Jong-Hwei

    2016-01-01

    IL-5-induced chemotaxis of eosinophils is an important feature of allergic airway inflammatory diseases. Simvastatin, a lipid lowering agent, has been shown to exhibit anti-inflammatory and anti-allergic effects. Our aim was to investigate the effect of simvastatin on IL-5-induced eosinophil chemotaxis and its regulatory mechanisms. Eosinophils were derived by treating HL-60 clone 15 (HC15) cells with butyric acid (BA) in an alkaline condition or through direct isolation from human peripheral blood. The expressions of CC chemokine receptor 3 (CCR3) and interleukin (IL)-5 receptors (IL5Rα and β) were analyzed using RT/real-time PCR. The granular proteins were stained using fast green. Eotaxin-induced chemotaxis was measured using a transwell migration assay. CCR3 protein expression was revealed by immunocytochemistry. An animal model of allergic rhinitis was established by challenging Sprague-Dawley® rats repeatedly with ovalbumin. Butyric acid significantly increased the expression of IL5Rα and IL5Rβ, CCR3 and granular proteins in HC15 cells, indicating the maturation of eosinophils (BA-E cells). IL-5 further enhanced the CCR3 expression at both the mRNA and protein levels and the eotaxin-induced chemotaxis of BA-E cells. Simvastatin inhibited the effects of IL-5 on BA-E cells, but not in the presence of mevalonate. Similar results were also exhibited in human primary eosinophils. In vivo animal studies further confirmed that oral simvastatin could significantly suppress the infiltration of eosinophils into turbinate tissues of allergic rats. Therefore, simvastatin was demonstrated to inhibit IL-5-induced CCR3 expression and chemotaxis of eosinophils mediated via the mevalonate pathway. We confirmed that simvastatin also reduced eosinophilic infiltration in allergic rhinitis.

  14. An Analysis of the Joints’ Properties of Fine-Grained Steel Welded by the MAG and SAW Methods

    Directory of Open Access Journals (Sweden)

    Krawczyk R.

    2016-09-01

    Full Text Available The article presents an analysis of properties of welded joints of fine-grained steel of P460NH type used more and more often in the modern constructions. A process of examining a technology of welding has been carried out on the thick-walled butt joints of sheet metal by two methods of welding namely MAG – 135 and SAW – 121. The article deals with a topic of optimizing a process of welding thick-walled welded joints of fine-grained steel due to their mechanicalproperties and efficiency.

  15. Classification of Magnetic Nanoparticle Systems—Synthesis, Standardization and Analysis Methods in the NanoMag Project

    Directory of Open Access Journals (Sweden)

    Sara Bogren

    2015-08-01

    Full Text Available This study presents classification of different magnetic single- and multi-core particle systems using their measured dynamic magnetic properties together with their nanocrystal and particle sizes. The dynamic magnetic properties are measured with AC (dynamical susceptometry and magnetorelaxometry and the size parameters are determined from electron microscopy and dynamic light scattering. Using these methods, we also show that the nanocrystal size and particle morphology determines the dynamic magnetic properties for both single- and multi-core particles. The presented results are obtained from the four year EU NMP FP7 project, NanoMag, which is focused on standardization of analysis methods for magnetic nanoparticles.

  16. MAG2GABA-biocytin synthesized with new intermediates for radiolabelling 99mTc and 188Re

    International Nuclear Information System (INIS)

    Ahn, S.H.; Choi, T.H.; Choi, C.W.; Yang, S.D.; Woo, K.S.; Chung, W.S.; Lim, S.M.

    2001-01-01

    188 Re from 188 W- 188 Re generator, is recently introduced in therapeutic nuclear medicine and made it possible to use whenever needed. We synthesized MAG 2 GABA-Biocytin (MGB), labelled with 188 Re for pretargeted radioimmunotherapy and evaluated biological behavior of 188 Re-MGB. N-hydroxysuccinimidyl ester of S-benzoyl mercaptoacetyldiglycine (NHS-MAG 2 ) was synthesized first, reacted with aminobutyric acid(GABA) to give MAG 2 GABA and then converted to NHS-MAG 2 GABA and conjugated to biocytin to give the MGB. To label MGB with 188 Re (50mA), ag, 200ml 1M tartrate pH7, 200 l stannous (10mg/mL) and 180MBq perrhenate were mixed and heated for 30min at 100 deg. C. The reactant was purified with C 18 Sep-Pak. HPLC analysis of the 188 Re-MGB performed on reverse phase C 18 column with a gradient. To see the stability, 188 Re-MGB was added to serum at 37 deg. C. Binding capacity of 188 Re-MGB to avidin or streptavidin was determined by size exclusion HPLC system. Biodistribution was studied in ICR normal mice(n=4/group), from 5min to 120min. In Raji cells tumour bearing nude mice(n=3), biotinylated Lym-1(40MEG) injection after 48 h, streptavidin(50MEG) was injected. 24 h later, 188 Re-MGB(0.5MEG) was injected, and biodistribution was observed 2 h later. 188 Re-MGB was obtained with labelling yield 98%. Stability in serum was maintained over 70% until 3 h. Binding capacity of 188 Re-MGB to streptavidin was greater than avidin. In normal mice, 188 Re-MGB was excreted via hepatobiliary pathway,%ID/g of GI tract was 52.1 at 120min. In Raji cells tumour bearing nude mice, liver and colon were higher than those of normal mouse. Tumour uptake at 120min was 0.05%ID/g. 188 Re-MGB was effectively labelled and retained binding activity with streptavidin. 188 Re-MGB may have a role in pretargeted radioimmunotherapy. (author)

  17. Dependence of the mechanical properties of joints welded according to the parameters of the metal active gas (MAG welding regime

    Directory of Open Access Journals (Sweden)

    D. Dobrotă

    2015-10-01

    Full Text Available The main objective followed in the realization of welded structures is to obtain superior mechanical characteristics for these structures. The research aimed at setting ranges of values for the welding voltage (Uw, respectively for the welding current (Iw so as to obtain superior mechanical features for welded constructions. The research was carried out using E 36-4 steel as base material and SG2 wire as filler material, whereas the applied welding process was MAG. The optimization was done with the help of a number of 31 test bars considering various welding procedures for each test bar, and the experimental data were processed using the STATISTCA program.

  18. Genetic Susceptibility to Cardiac and Digestive Clinical Forms of Chronic Chagas Disease: Involvement of the CCR5 59029 A/G Polymorphism.

    Science.gov (United States)

    de Oliveira, Amanda Priscila; Bernardo, Cássia Rubia; Camargo, Ana Vitória da Silveira; Ronchi, Luiz Sérgio; Borim, Aldenis Albaneze; de Mattos, Cinara Cássia Brandão; de Campos Júnior, Eumildo; Castiglioni, Lílian; Netinho, João Gomes; Cavasini, Carlos Eugênio; Bestetti, Reinaldo Bulgarelli; de Mattos, Luiz Carlos

    2015-01-01

    The clinical manifestations of chronic Chagas disease include the cardiac form of the disease and the digestive form. Not all the factors that act in the variable clinical course of this disease are known. This study investigated whether the CCR5Δ32 (rs333) and CCR5 59029 A/G (promoter region--rs1799987) polymorphisms of the CCR5 gene are associated with different clinical forms of chronic Chagas disease and with the severity of left ventricular systolic dysfunction in patients with chronic Chagas heart disease (CCHD). The antibodies anti-T. cruzi were identified by ELISA. PCR and PCR-RFLP were used to identify the CCR5Δ32 and CCR5 59029 A/G polymorphisms. The chi-square test was used to compare variables between groups. There was a higher frequency of the AA genotype in patients with CCHD compared with patients with the digestive form of the disease and the control group. The results also showed a high frequency of the AG genotype in patients with the digestive form of the disease compared to the other groups. The results of this study show that the CCR5Δ32 polymorphism does not seem to influence the different clinical manifestations of Chagas disease but there is involvement of the CCR5 59029 A/G polymorphism in susceptibility to the different forms of chronic Chagas disease. Besides, these polymorphisms do not influence left ventricular systolic dysfunction in patients with CCHD.

  19. Genetic Susceptibility to Cardiac and Digestive Clinical Forms of Chronic Chagas Disease: Involvement of the CCR5 59029 A/G Polymorphism.

    Directory of Open Access Journals (Sweden)

    Amanda Priscila de Oliveira

    Full Text Available The clinical manifestations of chronic Chagas disease include the cardiac form of the disease and the digestive form. Not all the factors that act in the variable clinical course of this disease are known. This study investigated whether the CCR5Δ32 (rs333 and CCR5 59029 A/G (promoter region--rs1799987 polymorphisms of the CCR5 gene are associated with different clinical forms of chronic Chagas disease and with the severity of left ventricular systolic dysfunction in patients with chronic Chagas heart disease (CCHD. The antibodies anti-T. cruzi were identified by ELISA. PCR and PCR-RFLP were used to identify the CCR5Δ32 and CCR5 59029 A/G polymorphisms. The chi-square test was used to compare variables between groups. There was a higher frequency of the AA genotype in patients with CCHD compared with patients with the digestive form of the disease and the control group. The results also showed a high frequency of the AG genotype in patients with the digestive form of the disease compared to the other groups. The results of this study show that the CCR5Δ32 polymorphism does not seem to influence the different clinical manifestations of Chagas disease but there is involvement of the CCR5 59029 A/G polymorphism in susceptibility to the different forms of chronic Chagas disease. Besides, these polymorphisms do not influence left ventricular systolic dysfunction in patients with CCHD.

  20. Characterization and analysis of CCR and CAD gene families at the whole-genome level for lignin synthesis of stone cells in pear (Pyrus bretschneideri) fruit.

    Science.gov (United States)

    Cheng, Xi; Li, Manli; Li, Dahui; Zhang, Jinyun; Jin, Qing; Sheng, Lingling; Cai, Yongping; Lin, Yi

    2017-11-15

    The content of stone cells has significant effects on the flavour and quality of pear fruit. Previous research suggested that lignin deposition is closely related to stone cell formation. In the lignin biosynthetic pathway, cinnamoyl-CoA reductase (CCR) and cinnamyl alcohol dehydrogenase (CAD), dehydrogenase/reductase family members, catalyse the last two steps in monolignol synthesis. However, there is little knowledge of the characteristics of the CCR and CAD families in pear and their involvement in lignin synthesis of stone cells. In this study, 31 CCR s and 26 CAD s were identified in the pear genome. Phylogenetic trees for CCR s and CAD s were constructed; key amino acid residues were analysed, and three-dimensional structures were predicted. Using quantitative real-time polymerase chain reaction (qRT-PCR), PbCAD2 , PbCCR1 , -2 and - 3 were identified as participating in lignin synthesis of stone cells in pear fruit. Subcellular localization analysis showed that the expressed proteins (PbCAD2, PbCCR1, -2 and -3) are found in the cytoplasm or at the cell membrane. These results reveal the evolutionary features of the CCR and CAD families in pear as well as the genes responsible for regulation of lignin synthesis and stone cell development in pear fruit. © 2017. Published by The Company of Biologists Ltd.

  1. Association between the CCR5 32-bp deletion allele and late onset of schizophrenia

    DEFF Research Database (Denmark)

    Rasmussen, H.B.; Timm, S.; Wang, A.G.

    2006-01-01

    OBJECTIVE: The 32-bp deletion allele in chemokine receptor CCR5 has been associated with several immune-mediated diseases and might be implicated in schizophrenia as well. METHOD: The authors genotyped DNA samples from 268 schizophrenia patients and 323 healthy subjects. Age at first admission...... to a psychiatric hospital department served as a measure of disease onset. RESULTS: Patients and comparison subjects differed marginally in their genotype distribution, with a slightly higher frequency of the deletion allele seen in the patients. The authors found the deletion allele to be associated with higher......-onset schizophrenia) and healthy subjects differed significantly. This was reflected in an increased frequency of the deletion allele in the patient subgroup. Patients with ages at first admission below and above 40 years significantly differed in distribution of genotypes and alleles, with an overrepresentation...

  2. Identification of pyrazolopyrimidine arylsulfonamides as CC-chemokine receptor 4 (CCR4) antagonists.

    Science.gov (United States)

    Miah, Afjal H; Champigny, Aurelie C; Graves, Rebecca H; Hodgson, Simon T; Percy, Jonathan M; Procopiou, Panayiotis A

    2017-10-15

    A novel 4-aminoindazole sulfonamide hit (13) was identified as a human CCR4 antagonists from testing a focussed library of compounds in the primary GTPγS assay. Replacing the indazole core with a pyrazolopyrimidine, and introduction of a methoxy group adjacent to the sulfonamide substituent, resulted in the identification of pyrazolopyrimidine 37a, which exhibited good binding affinity in the GTPγS assay (pIC 50 =7.2), low lipophilicity (clogP=2.2, chromlogD 7.4 =2.4), high LE (0.41), high solubility (CLND solubility ≥581µM), and an excellent PK profile in both the rat (F=62%) and the dog (F=100%). Further SAR investigation of the pyrazolopyrimidine suggested that substitution at N1 is tolerated, providing a suitable vector to modulate the properties, and increase the potency in a lead optimisation campaign. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. The geographic spread of the CCR5 Delta32 HIV-resistance allele.

    Directory of Open Access Journals (Sweden)

    John Novembre

    2005-11-01

    Full Text Available The Delta32 mutation at the CCR5 locus is a well-studied example of natural selection acting in humans. The mutation is found principally in Europe and western Asia, with higher frequencies generally in the north. Homozygous carriers of the Delta32 mutation are resistant to HIV-1 infection because the mutation prevents functional expression of the CCR5 chemokine receptor normally used by HIV-1 to enter CD4+ T cells. HIV has emerged only recently, but population genetic data strongly suggest Delta32 has been under intense selection for much of its evolutionary history. To understand how selection and dispersal have interacted during the history of the Delta32 allele, we implemented a spatially explicit model of the spread of Delta32. The model includes the effects of sampling, which we show can give rise to local peaks in observed allele frequencies. In addition, we show that with modest gradients in selection intensity, the origin of the Delta32 allele may be relatively far from the current areas of highest allele frequency. The geographic distribution of the Delta32 allele is consistent with previous reports of a strong selective advantage (>10% for Delta32 carriers and of dispersal over relatively long distances (>100 km/generation. When selection is assumed to be uniform across Europe and western Asia, we find support for a northern European origin and long-range dispersal consistent with the Viking-mediated dispersal of Delta32 proposed by G. Lucotte and G. Mercier. However, when we allow for gradients in selection intensity, we estimate the origin to be outside of northern Europe and selection intensities to be strongest in the northwest. Our results describe the evolutionary history of the Delta32 allele and establish a general methodology for studying the geographic distribution of selected alleles.

  4. Effects of treatment with Maraviroc a CCR5 inhibitor on a human hepatic stellate cell line.

    Science.gov (United States)

    Coppola, Nicola; Perna, Angelica; Lucariello, Angela; Martini, Salvatore; Macera, Margherita; Carleo, Maria A; Guerra, Germano; Esposito, Vincenzo; De Luca, Antonio

    2018-08-01

    After an acute liver damage, tissue regeneration repairs lesions with degradation of deposed fibrotic material, while mechanisms of tissue restoration are persistently activated following several repeated injuries, inducing deposition of extracellular matrix. (ECM). Factors responsible for ECM remodeling have been identified in a pathway involving a family of zinc-dependent enzyme matrix metalloproteinases (MMPs), together with tissue inhibitor of metalloproteinases (TIMPs). Recent experimental models suggested a role of CCR5 receptor in the genesis of liver fibrosis. Drawing from these background we decided to evaluate the effects of the treatment with the CCR5 inhibitor Maraviroc on LX-2, a human hepatic stellate cell line (HSC). Treatment with Maraviroc resulted in a block in S phase of LX-2 cells with increased expression levels of cyclin D1 and p21 while the expression of p53 was reduced. Treatment with Maraviroc was also able to block the accumulation of fibrillar collagens and extracellular matrix proteins (ECM), as demonstrated by the decrease of specific markers as Collagen type I, α-SMA, and TGF-β1. In addition we observed a down regulation of both metalloproteins (MMP-2, MMP-9), used for the degradation of the extracellular matrix and their inhibitors (TIMP-1, TIMP-2). The identification of a compound that may modulate the dynamic of liver fibrosis could be crucial in all chronic liver diseases. Maraviroc could play an important role because, in addition to its own anti-HIV activity, it could reduce the release of pro-inflammatory citokynes implicated in liver fibrogenesis. © 2018 Wiley Periodicals, Inc.

  5. The simultaneous repression of CCR and CAD, two enzymes of the lignin biosynthetic pathway, results in sterility and dwarfism in Arabidopsis thaliana.

    Science.gov (United States)

    Thévenin, Johanne; Pollet, Brigitte; Letarnec, Bruno; Saulnier, Luc; Gissot, Lionel; Maia-Grondard, Alessandra; Lapierre, Catherine; Jouanin, Lise

    2011-01-01

    Cinnamoyl CoA reductase (CCR) and cinnamyl alcohol dehydrogenase (CAD) catalyze the last steps of monolignol biosynthesis. In Arabidopsis, one CCR gene (CCR1, At1g15950) and two CAD genes (CAD C At3g19450 and CAD D At4g34230) are involved in this pathway. A triple cad c cad d ccr1 mutant, named ccc, was obtained. This mutant displays a severe dwarf phenotype and male sterility. The lignin content in ccc mature stems is reduced to 50% of the wild-type level. In addition, stem lignin structure is severely affected, as shown by the dramatic enrichment in resistant inter-unit bonds and incorporation into the polymer of monolignol precursors such as coniferaldehyde, sinapaldehyde, and ferulic acid. Male sterility is due to the lack of lignification in the anther endothecium, which causes the failure of anther dehiscence and of pollen release. The ccc hypolignified stems accumulate higher amounts of flavonol glycosides, sinapoyl malate and feruloyl malate, which suggests a redirection of the phenolic pathway. Therefore, the absence of CAD and CCR, key enzymes of the monolignol pathway, has more severe consequences on the phenotype than the individual absence of each of them. Induction of another CCR (CCR2, At1g80820) and another CAD (CAD1, At4g39330) does not compensate the absence of the main CCR and CAD activities. This lack of CCR and CAD activities not only impacts lignification, but also severely affects the development of the plants. These consequences must be carefully considered when trying to reduce the lignin content of plants in order to facilitate the lignocellulose-to-bioethanol conversion process.

  6. CCR9 interactions support ovarian cancer cell survival and resistance to cisplatin-induced apoptosis in a PI3K-dependent and FAK-independent fashion

    Directory of Open Access Journals (Sweden)

    Johnson Erica L

    2010-06-01

    Full Text Available Abstract Background Cisplatin is more often used to treat ovarian cancer (OvCa, which provides modest survival advantage primarily due to chemo-resistance and up regulated anti-apoptotic machineries in OvCa cells. Therefore, targeting the mechanisms responsible for cisplatin resistance in OvCa cell may improve therapeutic outcomes. We have shown that ovarian cancer cells express CC chemokine receptor-9 (CCR9. Others have also shown that CCL25, the only natural ligand for CCR9, up regulates anti-apoptotic proteins in immature T lymphocytes. Hence, it is plausible that CCR9-mediated cell signals might be involved in OvCa cell survival and inhibition of cisplatin-induced apoptosis. In this study, we investigated the potential role and molecular mechanisms of CCR9-mediated inhibition of cisplatin-induced apoptosis in OvCa cells. Methods Cell proliferation, vibrant apoptosis, and TUNEL assays were performed with or without cisplatin treatment in presence or absence of CCL25 to determine the role of the CCR9-CCL25 axis in cisplatin resistance. In situ Fast Activated cell-based ELISA (FACE assays were performed to determine anti-apoptotic signaling molecules responsible for CCL25-CCR9 mediated survival. Results Our results show interactions between CCR9 and CCL25 increased anti-apoptotic signaling cascades in OvCa cells, which rescued cells from cisplatin-induced cell death. Specifically, CCL25-CCR9 interactions mediated Akt, activation as well as GSK-3β and FKHR phosphorylation in a PI3K-dependent and FAK-independent fashion. Conclusions Our results suggest the CCR9-CCL25 axis plays an important role in reducing cisplatin-induced apoptosis of OvCa cells.

  7. 76 FR 20835 - Amendment of VOR Federal Airways V-1, V-7, V-11 and V-20; Kona, HI

    Science.gov (United States)

    2011-04-14

    ...; Airspace Docket No. 10-AWP-20] Amendment of VOR Federal Airways V-1, V-7, V-11 and V-20; Kona, HI AGENCY..., HI; V-1, V-7, V-11 and V-20. The FAA is taking this action due to procedural changes requiring..., (76 FR 13082), amends VOR Federal Airways V-1, V-7 V-11 and V-20; Kona, HI. These VHF Omnidirectional...

  8. Laparoendoscopic single site (LESS) in vivo suturing using a magnetic anchoring and guidance system (MAGS) camera in a porcine model: impact on ergonomics and workload.

    Science.gov (United States)

    Yin, Gang; Han, Woong Kyu; Faddegon, Stephen; Tan, Yung Khan; Liu, Zhuo-Wei; Olweny, Ephrem O; Scott, Daniel J; Cadeddu, Jeffrey A

    2013-01-01

    To compare the ergonomics and workload of the surgeon during single-site suturing while using the magnetic anchoring and guidance system (MAGS) camera vs a conventional laparoscope. Seven urologic surgeons were enrolled and divided into an expert group (n=2) and a novice group (n=5) according to their laparoendoscopic single-site (LESS) experience. Each surgeon performed 2 conventional LESS and 2 MAGS camera-assisted LESS vesicostomy closures in a porcine model. A Likert scale (scoring 1-5) questionnaire assessing workload, ergonomics, technical difficulty, visualization, and needle handling, as well as a validated National Aeronautics and Space Administration Task Load Index (NASA-TLX) questionnaire were used to evaluate the tasks and workloads. MAGS LESS suturing was universally favored by expert and novice surgeons compared with conventional LESS in workload (3.4 vs 4.2), ergonomics (3.4 vs 4.4), technical challenge (3.3 vs 4.3), visualization (2.4 vs 3.3), and needle handling (3.1 vs 3.9 respectively; PNASA-TLX assessments found MAGS LESS suturing significantly decreased the workload in physical demand (P=.004), temporal demand (P=.017), and effort (P=.006). External instrument clashing was significantly reduced in MAGS LESS suturing (P<.001). The total operative time of MAGS LESS suturing was comparable to that of conventional LESS (P=.89). MAGS camera technology significantly decreased surgeon workload and improved ergonomics. Nevertheless, LESS suturing and knot tying remains a challenging task that requires training, regardless of which camera is used. Copyright © 2013 Elsevier Inc. All rights reserved.

  9. Demonstration of Adaptive Functional Differences Seen in Kidneys Accompanying a Nonfunctioning/Hypofunctioning Partner, using Camera Based Tc 99m MAG3 Clearance Measurement Technique

    Directory of Open Access Journals (Sweden)

    Burcu Esen Akkaş

    2012-08-01

    Full Text Available Objective: The aim of this study was to demonstrate the functional compensation that occurs in kidneys which accompany a partner with total or partial loss of renal functioning mass, using camera-based Tc 99m MAG3 clearance technique. Material and Methods: Eighty five patients (43M, 42F, age: 44.8±12.6, range: 18-77 years with normal serum creatinine levels and normal (MAG3 renogram curves were enrolled for this retrospective study. Patients were grouped as having; group 1: solitary normal kidney (unilateral atrophied/agenetic (n=23, group 2: normal kidney with contralateral hypoplasic/hypofunctioning kidney (split renal function<30%, (n=24, group 3: bilateral normal kidneys (n=38. The measured camera based Tc 99m MAG3 clearances of normal kidneys in each group were compared. Results: Total Tc 99m MAG3 clearances (mL/min/1.73m 2 were significantly lower in group 1 and group 2 compared to group 3 (281.5±46, 260.5±61.7 and 316.1±84, respectively. Highest isolated Tc 99m MAG3 clearances among normal functioning kidneys were observed in group 1 (281.5±45.6 followed by group 2 (204.4±55 and group 3 (157.5±44. Moderate negative correlation was detected between the Tc99m MAG3 clearances of normal kidneys and contralateral renal function (r=-0.5, p<0.001. Conclusion: Normal kidneys can compensate for the loss of contralateral kidney function via increasing their clearances, which seems to be dependent on the residual function of their partner. Camera based Tc 99m MAG3 clearance measurement is an objective method to demonstrate compensatory differences in renal function seen between kidneys with contralateral normofunctioning, hypofunctioning and nonfunctioning partner. (MIRT 2012;21:56-62

  10. Pharmacokinetics of {sup 99m}Tc-MAG{sub 3} and {sup 131}I-OIH. Comparative study based on 2 compartment model analysis

    Energy Technology Data Exchange (ETDEWEB)

    Shuke, Noriyuki; Takashio, Tetsuya; Sato, Junichi [Asahikawa Medical Coll., Hokkaido (Japan). Hospital] [and others

    1996-05-01

    We studied 50 patients with mild to moderate renal dysfunction to compare pharmacokinetics of {sup 99m}Tc-MAG{sub 3} with that of {sup 131}I-OIH. After simultaneous bolus injection of both {sup 99m}Tc-MAG{sub 3} and {sup 131}I-OIH, 8-point venous blood sampling was performed from 2 to 44 min post injection. Aliquoted plasma samples were counted for radioactivity along with the injected standard to obtain % injected dose/ml plasma for each tracer. Using obtained time-concentration data, classical 2 compartment model analysis was performed for both tracers to obtain various pharmacokinetic parameters, including distribution volumes (Vds), intercompartmental rate constants, and plasma clearance. In these parameters, Vd of central compartment, Vd at steady state, central to peripheral inter-compartmental rate constant, and plasma clearance were significantly larger for {sup 131}I-OIH. In all parameters, significant correlation was found between {sup 99m}Tc-MAG{sub 3} and {sup 131}I-OIH. The best correlation was seen in plasma clearance (r=0.891, p<0.0001). Plasma clearance ratio ({sup 99m}Tc-MAG{sub 3}/{sup 131}I-OIH), however, showed weak but significant negative correlation with serum creatinine, although this correlation was not likely to affect the overall correlation of clearance between {sup 131}I-OIH and {sup 99m}Tc-MAG{sub 3}. From these results, we comfirmed that {sup 99m}Tc-MAG{sub 3} clearance could be used as an alternative to {sup 131}I-OIH clearance, although pharmacokinetic behavior of {sup 99m}Tc-MAG{sub 3} was not exactly the same as that of {sup 131}I-OIH. (author)

  11. The structure of mAG, a monomeric mutant of the green fluorescent protein Azami-Green, reveals the structural basis of its stable green emission

    International Nuclear Information System (INIS)

    Ebisawa, Tatsuki; Yamamura, Akihiro; Kameda, Yasuhiro; Hayakawa, Kou; Nagata, Koji; Tanokura, Masaru

    2010-01-01

    The crystal structure of a monomeric mutant of Azami-Green (mAG) from G. fascicularis was determined at 2.2 Å resolution. Monomeric Azami-Green (mAG) from the stony coral Galaxea fascicularis is the first known monomeric green-emitting fluorescent protein that is not a variant of Aequorea victoria green fluorescent protein (avGFP). These two green fluorescent proteins are only 27% identical in their amino-acid sequences. mAG is more similar in its amino-acid sequence to four fluorescent proteins: Dendra2 (a green-to-red irreversibly photoconverting fluorescent protein), Dronpa (a bright-and-dark reversibly photoswitchable fluorescent protein), KikG (a tetrameric green-emitting fluorescent protein) and Kaede (another green-to-red irreversibly photoconverting fluorescent protein). To reveal the structural basis of stable green emission by mAG, the 2.2 Å crystal structure of mAG has been determined and compared with the crystal structures of avGFP, Dronpa, Dendra2, Kaede and KikG. The structural comparison revealed that the chromophore formed by Gln62-Tyr63-Gly64 (QYG) and the fixing of the conformation of the imidazole ring of His193 by hydrogen bonds and van der Waals contacts involving His193, Arg66 and Thr69 are likely to be required for the stable green emission of mAG. The crystal structure of mAG will contribute to the design and development of new monomeric fluorescent proteins with faster maturation, brighter fluorescence, improved photostability, new colours and other preferable properties as alternatives to avGFP and its variants

  12. Genetic Susceptibility to Cardiac and Digestive Clinical Forms of Chronic Chagas Disease: Involvement of the CCR5 59029 A/G Polymorphism

    OpenAIRE

    de Oliveira, Amanda Priscila; Bernardo, C?ssia Rubia; Camargo, Ana Vit?ria da Silveira; Ronchi, Luiz S?rgio; Borim, Aldenis Albaneze; Brand?o de Mattos, Cinara C?ssia; de Campos J?nior, Eumildo; Castiglioni, L?lian; Netinho, Jo?o Gomes; Cavasini, Carlos Eug?nio; Bestetti, Reinaldo Bulgarelli; de Mattos, Luiz Carlos

    2015-01-01

    The clinical manifestations of chronic Chagas disease include the cardiac form of the disease and the digestive form. Not all the factors that act in the variable clinical course of this disease are known. This study investigated whether the CCR5Δ32 (rs333) and CCR5 59029 A/G (promoter region--rs1799987) polymorphisms of the CCR5 gene are associated with different clinical forms of chronic Chagas disease and with the severity of left ventricular systolic dysfunction in patients with chronic C...

  13. Chemokine CCL2–CCR2 Signaling Induces Neuronal Cell Death via STAT3 Activation and IL-1β Production after Status Epilepticus

    Science.gov (United States)

    Tian, Dai-Shi; Feng, Li-Jie; Liu, Jun-Li

    2017-01-01

    Elevated levels of chemokine C-C motif ligand 2 (CCL2) and its receptor CCR2 have been reported in patients with temporal lobe epilepsy and in experimental seizures. However, the functional significance and molecular mechanism underlying CCL2–CCR2 signaling in epileptic brain remains largely unknown. In this study, we found that the upregulated CCL2 was mainly expressed in hippocampal neurons and activated microglia from mice 1 d after kainic acid (KA)-induced seizures. Taking advantage of CX3CR1GFP/+:CCR2RFP/+ double-transgenic mice, we demonstrated that CCL2–CCR2 signaling has a role in resident microglial activation and blood-derived monocyte infiltration. Moreover, seizure-induced degeneration of neurons in the hippocampal CA3 region was attenuated in mice lacking CCL2 or CCR2. We further showed that CCR2 activation induced STAT3 (signal transducer and activator of transcription 3) phosphorylation and IL-1β production, which are critical for promoting neuronal cell death after status epilepticus. Consistently, pharmacological inhibition of STAT3 by WP1066 reduced seizure-induced IL-1β production and subsequent neuronal death. Two weeks after KA-induced seizures, CCR2 deficiency not only reduced neuronal loss, but also attenuated seizure-induced behavioral impairments, including anxiety, memory decline, and recurrent seizure severity. Together, we demonstrated that CCL2–CCR2 signaling contributes to neurodegeneration via STAT3 activation and IL-1β production after status epilepticus, providing potential therapeutic targets for the treatment of epilepsy. SIGNIFICANCE STATEMENT Epilepsy is a global concern and epileptic seizures occur in many neurological conditions. Neuroinflammation associated with microglial activation and monocyte infiltration are characteristic of epileptic brains. However, molecular mechanisms underlying neuroinflammation in neuronal death following epilepsy remain to be elucidated. Here we demonstrate that CCL2–CCR2 signaling is

  14. Tackling Bet v 1 and associated food allergies with a single hybrid protein.

    Science.gov (United States)

    Hofer, Heidi; Asam, Claudia; Hauser, Michael; Nagl, Birgit; Laimer, Josef; Himly, Martin; Briza, Peter; Ebner, Christof; Lang, Roland; Hawranek, Thomas; Bohle, Barbara; Lackner, Peter; Ferreira, Fátima; Wallner, Michael

    2017-08-01

    Allergy vaccines should be easily applicable, safe, and efficacious. For Bet v 1-mediated birch pollen and associated food allergies, a single wild-type allergen does not provide a complete solution. We aimed to combine immunologically relevant epitopes of Bet v 1 and the 2 clinically most important related food allergens from apple and hazelnut to a single hybrid protein, termed MBC4. After identification of T cell epitope-containing parts on each of the 3 parental allergens, the hybrid molecule was designed to cover relevant epitopes and evaluated in silico. Thereby a mutation was introduced into the hybrid sequence, which should alter the secondary structure without compromising the immunogenic properties of the molecule. MBC4 and the parental allergens were purified to homogeneity. Analyses of secondary structure elements revealed substantial changes rendering the hybrid de facto nonreactive with patients' serum IgE. Nevertheless, the protein was monomeric in solution. MBC4 was able to activate T-cell lines from donors with birch pollen allergy and from mice immunized with the parental allergens. Moreover, on immunization of mice and rabbits, MBC4 induced cross-reactive IgG antibodies, which were able to block the binding of human serum IgE. Directed epitope rearrangements combined with a knowledge-based structural modification resulted in a protein unable to bind IgE from allergic patients. Still, properties to activate specific T cells or induce blocking antibodies were conserved. This suggests that MBC4 is a suitable vaccine candidate for the simultaneous treatment of Bet v 1 and associated food allergies. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  15. Contextual modulation revealed by optical imaging exhibits figural asymmetry in macaque V1 and V2

    Directory of Open Access Journals (Sweden)

    Zarella MD

    2017-04-01

    Full Text Available Mark D Zarella, Daniel Y Ts’o Department of Neurosurgery, SUNY Upstate Medical University, Syracuse, NY, USA Abstract: Neurons in early visual cortical areas are influenced by stimuli presented well beyond the confines of their classical receptive fields, endowing them with the ability to encode fine-scale features while also having access to the global context of the visual scene. This property can potentially define a role for the early visual cortex to contribute to a number of important visual functions, such as surface segmentation and figure–ground segregation. It is unknown how extraclassical response properties conform to the functional architecture of the visual cortex, given the high degree of functional specialization in areas V1 and V2. We examined the spatial relationships of contextual activations in macaque V1 and V2 with intrinsic signal optical imaging. Using figure–ground stimulus configurations defined by orientation or motion, we found that extraclassical modulation is restricted to the cortical representations of the figural component of the stimulus. These modulations were positive in sign, suggesting a relative enhancement in neuronal activity that may reflect an excitatory influence. Orientation and motion cues produced similar patterns of activation that traversed the functional subdivisions of V2. The asymmetrical nature of the enhancement demonstrated the capacity for visual cortical areas as early as V1 to contribute to figure–ground segregation, and the results suggest that this information can be extracted from the population activity constrained only by retinotopy, and not the underlying functional organization. Keywords: striate, extrastriate, segmentation, figure–ground, functional organization

  16. Outbursting comet P/2010 V1 (Ikeya-Murakami): A miniature comet Holmes

    Energy Technology Data Exchange (ETDEWEB)

    Ishiguro, Masateru [Department of Physics and Astronomy, Seoul National University, Gwanak, Seoul 151-742 (Korea, Republic of); Jewitt, David [Department of Earth, Planetary and Space Sciences, University of California at Los Angeles, 595 Charles Young Drive East, Los Angeles, CA 90095-1567 (United States); Hanayama, Hidekazu; Miyaji, Takeshi; Fukushima, Hideo; Watanabe, Jun-ichi [Ishigakijima Astronomical Observatory, National Astronomical Observatory of Japan, Ishigaki, Okinawa 907-0024 (Japan); Usui, Fumihiko [Department of Astronomy, Graduate School of Science, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033 (Japan); Sekiguchi, Tomohiko [Department of Teacher Training, Hokkaido University of Education, 9 Hokumon, Asahikawa 070-8621 (Japan); Yanagisawa, Kenshi; Kuroda, Daisuke [Okayama Astrophysical Observatory, National Astronomical Observatory of Japan, Asaguchi, Okayama 719-0232 (Japan); Yoshida, Michitoshi [Hiroshima Astrophysical Science Center, Hiroshima University, 1-3-1 Kagamiyama, Higashi-Hiroshima, Hiroshima 739-8526 (Japan); Ohta, Kouji [Department of Astronomy, Kyoto University, Kyoto 606-8502 (Japan); Kawai, Nobuyuki [Department of Physics, Tokyo Institute of Technology, 2-12-1 Ookayama, Meguro-ku, Tokyo 152-8551 (Japan)

    2014-05-20

    The short-period comet P/2010 V1 (Ikeya-Murakami, hereafter {sup V}1{sup )} was discovered visually by two amateur astronomers. The appearance of the comet was peculiar, consisting of an envelope, a spherical coma near the nucleus and a tail extending in the anti-solar direction. We investigated the brightness and the morphological development of the comet by taking optical images with ground-based telescopes. Our observations show that V1 experienced a large-scale explosion between UT 2010 October 31 and November 3. The color of the comet was consistent with the Sun (g' – R {sub C} = 0.61 ± 0.20, R {sub C} – I {sub C} = 0.20 ± 0.20, and B – R {sub C} = 0.93 ± 0.25), suggesting that dust particles were responsible for the brightening. We used a dynamical model to understand the peculiar morphology, and found that the envelope consisted of small grains (0.3-1 μm) expanding at a maximum speed of 500 ± 40 m s{sup –1}, while the tail and coma were composed of a wider range of dust particle sizes (0.4-570 μm) and expansion speeds 7-390 m s{sup –1}. The total mass of ejecta is ∼5 × 10{sup 8} kg and kinetic energy ∼5 × 10{sup 12} J. These values are much smaller than in the historic outburst of 17P/Holmes in 2007, but the energy per unit mass (1 × 10{sup 4} J kg{sup –1}) is comparable. The energy per unit mass is about 10% of the energy released during the crystallization of amorphous water ice suggesting that crystallization of buried amorphous ice can supply the mass and energy of the outburst ejecta.

  17. Serotonin Decreases the Gain of Visual Responses in Awake Macaque V1.

    Science.gov (United States)

    Seillier, Lenka; Lorenz, Corinna; Kawaguchi, Katsuhisa; Ott, Torben; Nieder, Andreas; Pourriahi, Paria; Nienborg, Hendrikje

    2017-11-22

    Serotonin, an important neuromodulator in the brain, is implicated in affective and cognitive functions. However, its role even for basic cortical processes is controversial. For example, in the mammalian primary visual cortex (V1), heterogenous serotonergic modulation has been observed in anesthetized animals. Here, we combined extracellular single-unit recordings with iontophoresis in awake animals. We examined the role of serotonin on well-defined tuning properties (orientation, spatial frequency, contrast, and size) in V1 of two male macaque monkeys. We find that in the awake macaque the modulatory effect of serotonin is surprisingly uniform: it causes a mainly multiplicative decrease of the visual responses and a slight increase in the stimulus-selective response latency. Moreover, serotonin neither systematically changes the selectivity or variability of the response, nor the interneuronal correlation unexplained by the stimulus ("noise-correlation"). The modulation by serotonin has qualitative similarities with that for a decrease in stimulus contrast, but differs quantitatively from decreasing contrast. It can be captured by a simple additive change to a threshold-linear spiking nonlinearity. Together, our results show that serotonin is well suited to control the response gain of neurons in V1 depending on the animal's behavioral or motivational context, complementing other known state-dependent gain-control mechanisms. SIGNIFICANCE STATEMENT Serotonin is an important neuromodulator in the brain and a major target for drugs used to treat psychiatric disorders. Nonetheless, surprisingly little is known about how it shapes information processing in sensory areas. Here we examined the serotonergic modulation of visual processing in the primary visual cortex of awake behaving macaque monkeys. We found that serotonin mainly decreased the gain of the visual responses, without systematically changing their selectivity, variability, or covariability. This

  18. Evaluation of renal allograft dysfunction employing dynamic SPECT with 99mTc-MAG3 and graph plot analysis

    International Nuclear Information System (INIS)

    Akahira, Hideaki

    1996-01-01

    To estimate renal blood flow and tubular function in transplanted kidneys, we applied the 4 compartments model and the graphic analysis method to 99m Tc-MAG3 dynamic SPECT and calculated some parameters, i.e. K1 (renal influx rate constant), K3 (tubular transporting rate constant), Vd12 (intrarenal distribution volume), and others. Twenty-three renal transplant recipients were examined and divided into following 3 groups according to their serum creatinine levels (SCr); Group I: less than 13 mg/dl (1.1±0.3, n=7), Group II: 1.4-2.5 mg/dl (1.8±0.3, n=11), and Group III more than 2.6 mg/dl (3.9±0.9, n=5). The K3 value became lower in the order of Group I>II>III, and well correlated with blood urea nitrogen (BUN, r=-0.95, p 99m Tc-MAG3 uptake function, respectively. (author)

  19. Magnetic flux and heat losses by diffusive, advective, and Nernst effects in MagLIF-like plasma

    International Nuclear Information System (INIS)

    Velikovich, A. L.; Giuliani, J. L.; Zalesak, S. T.

    2014-01-01

    The MagLIF approach to inertial confinement fusion involves subsonic/isobaric compression and heating of a DT plasma with frozen-in magnetic flux by a heavy cylindrical liner. The losses of heat and magnetic flux from the plasma to the liner are thereby determined by plasma advection and gradient-driven transport processes, such as thermal conductivity, magnetic field diffusion and thermomagnetic effects. Theoretical analysis based on obtaining exact self-similar solutions of the classical collisional Braginskii's plasma transport equations in one dimension demonstrates that the heat loss from the hot plasma to the cold liner is dominated by the transverse heat conduction and advection, and the corresponding loss of magnetic flux is dominated by advection and the Nernst effect. For a large electron Hall parameter ω e τ e effective diffusion coefficients determining the losses of heat and magnetic flux are both shown to decrease with ω e τ e as does the Bohm diffusion coefficient, which is commonly associated with low collisionality and two-dimensional transport. This family of exact solutions can be used for verification of codes that model the MagLIF plasma dynamics

  20. The importance of binder moisture content in Metformin HCL high-dose formulations prepared by moist aqueous granulation (MAG

    Directory of Open Access Journals (Sweden)

    Hiroshi Takasaki

    2015-01-01

    Full Text Available The aim of this study was to evaluate binders to improve the flowability of granulates and compactibility of Metformin HCL (Met using the moist aqueous granulation (MAG process. The effect of the binder moisture content on granulate and tablet quality was also evaluated. Vinylpyrrolidone–vinyl acetate copolymer (Kollidon VA64 fine: VA64, polyvidone (Povidone K12: PVP, hydroxypropyl cellulose (HPC SSL SF: HPC and hydroxypropyl methylcellulose (Methocel E5 LV: HPMC were evaluated as binders. These granulates, except for HPMC, had a lower yield pressure than Met active pharmaceutical ingredient (API. HPMC Met was not sufficiently granulated with low water volume. No problems were observed with the VA64 Met granulates during the tableting process. However, HPC Met granulates had a bowl-forming tendency, and PVP Met granulates had the tendency to stick during the tableting process. These bowl-forming and sticking tendencies may have been due to the low moisture absorbency of HPC and the high volume of bound water of PVP, respectively. VA64 Met granulates had the highest ambient moisture content (bulk water, bound water and moisture absorbency. It was concluded that the type of binder used for the Met MAG process has an impact on granulate flow and compactibility, as well as moisture absorbency and maintenance of moisture balance.