WorldWideScience

Sample records for upward flux fc

  1. Simulation of upward flux from shallow water-table using UPFLOW model

    Directory of Open Access Journals (Sweden)

    M. H. Ali

    2013-11-01

    Full Text Available The upward movement of water by capillary rise from shallow water-table to the root zone is an important incoming flux. For determining exact amount of irrigation requirement, estimation of capillary flux or upward flux is essential. Simulation model can provide a reliable estimate of upward flux under variable soil and climatic conditions. In this study, the performance of model UPFLOW to estimate upward flux was evaluated. Evaluation of model performance was performed with both graphical display and statistical criteria. In distribution of simulated capillary rise values against observed field data, maximum data points lie around the 1:1 line, which means that the model output is reliable and reasonable. The coefficient of determination between observed and simulated values was 0.806 (r = 0.93, which indicates a good inter-relation between observed and simulated values. The relative error, model efficiency, and index of agreement were found as 27.91%, 85.93% and 0.96, respectively. Considering the graphical display of observed and simulated upward flux and statistical indicators, it can be concluded that the overall performance of the UPFLOW model in simulating actual upward flux from a crop field under variable water-table condition is satisfactory. Thus, the model can be used to estimate capillary rise from shallow water-table for proper estimation of irrigation requirement, which would save valuable water from over-irrigation.

  2. High Upward Fluxes of Formic Acid from a Boreal Forest Canopy

    Science.gov (United States)

    Schobesberger, Siegfried; Lopez-Hilifiker, Felipe D.; Taipale, Ditte; Millet, Dylan B.; D'Ambro, Emma L.; Rantala, Pekka; Mammarella, Ivan; Zhou, Putian; Wolfe, Glenn M.; Lee, Ben H.; hide

    2016-01-01

    Eddy covariance fluxes of formic acid, HCOOH, were measured over a boreal forest canopy in spring/summer 2014. The HCOOH fluxes were bidirectional but mostly upward during daytime, in contrast to studies elsewhere that reported mostly downward fluxes. Downward flux episodes were explained well by modeled dry deposition rates. The sum of net observed flux and modeled dry deposition yields an upward gross flux of HCOOH, which could not be quantitatively explained by literature estimates of direct vegetative soil emissions nor by efficient chemical production from other volatile organic compounds, suggesting missing or greatly underestimated HCOOH sources in the boreal ecosystem. We implemented a vegetative HCOOH source into the GEOS-Chem chemical transport model to match our derived gross flux and evaluated the updated model against airborne and spaceborne observations. Model biases in the boundary layer were substantially reduced based on this revised treatment, but biases in the free troposphere remain unexplained.

  3. Intensity of Upward Muon Flux Due to Cosmic-Ray Neutrinos Produced in the Atmosphere

    Science.gov (United States)

    Lee, T. D.; Robinson, H.; Schwartz, M.; Cool, R.

    1963-06-01

    Calculations were performed to determine the upward going muon flux leaving the earth's surface after production by cosmic-ray neutrinos in the crust. Only neutrinos produced in the earth's atmosphere are considered. Rates of the order of one per 100 sq m/day might be expected if an intermediate boson exists and has a mass less than 2 Bev. (auth)

  4. Dry-out heat fluxes of falling film and low-mass flux upward-flow in heated tubes

    International Nuclear Information System (INIS)

    Koizumi, Yasuo; Ueda, Tatsuhiro; Matsuo, Teruyuki; Miyota, Yukio

    1998-01-01

    Dry-out heat fluxes were investigated experimentally for a film flow falling down on the inner surface of vertical heated-tubes and for a low mass flux forced-upward flow in the tubes using R 113. This work followed the study on those for a two-phase natural circulation system. For the falling film boiling, flow state observation tests were also performed, where dry-patches appearing and disappearing repeatedly were observed near the exit end of the heated section at the dry-out heat flux conditions. Relation between the dry-out heat flux and the liquid film flow rate is analyzed. The dry-out heat fluxes of the low mass flux upflow are expressed well by the correlation proposed in the previous work. The relation for the falling film boiling shows a similar trend to that for the upflow boiling, however, the dry-out heat fluxes of the falling film are much lower, approximately one third, than those of the upward flow. (author)

  5. Evaluation of upward heat flux in ex-vessel molten core heat transfer using MELCOR

    International Nuclear Information System (INIS)

    Park, S.Y.; Park, J.H.; Kim, S.D.; Kim, D.H.; Kim, H.D.

    2000-01-01

    The purpose of this study is to share experiences of MELCOR application to resolve the molten corium-concrete interaction (MCCI) issue in the Korea Next Generation Reactor (KNGR). In the evaluation of concrete erosion, the heat transfer modeling from the molten corium internal to the corium pool surface is very important and uncertain. MELCOR employs Kutateladze or Greene's bubble-enhanced heat transfer model for the internal heat transfer. The phenomenological uncertainty is so large that the model provides several model parameters in addition to the phenomenological model for user flexibility. However, the model parameters do not work on Kutateladze correlation at the top of the molten layer. From our experience, a code modification is suggested to match the upward heat flux with the experimental results. In this analysis, minor modification was carried out to calculate heat flux from the top molten layer to corium surface, and efforts were made to find out the best value of the model parameter based on upward heat flux of MACE test M1B. Discussion also includes its application to KNGR. (author)

  6. Drift-flux parameters for upward gas flow in stagnant liquid

    International Nuclear Information System (INIS)

    Kataoka, Yoshiyuki; Suzuki, Hiroaki; Murase, Michio

    1987-01-01

    The drift-flux model is widely used for gas-liquid two phase flow analysis, because it is applicable to various flow patterns and a wide range of void fractions. The drift-flux parameters for upward gas flow in stagnant liquid, however, have not been well examined. In this study, the distribution parameter C o and the drift velocity V gj for stagnant liquid were derived from the void fraction correlation and boundary conditions of drift-flux parameters, and then compared with C o and V gj for high liquid velocities. Also using the two region model where a circular flow area was divided into an inner region of cocurrent up-flow and an outer annulus region of liquid down flow, C o and V gj for stagnant liquid and for high liquid velocity were compared. The results showed that C o values for stagnant liquid were larger than values for high liquid velocity, while V gj values were almost the same for both cases. (author)

  7. Critical heat flux in a vertical annulus under low upward flow and near atmospheric pressure

    International Nuclear Information System (INIS)

    Schoesse, T.; Aritomi, Masanori; Lee, Sang-Ryoul; Kataoka, Yoshiaki; Yoshioka, Yuzuru; Chung, Moon-Ki.

    1997-01-01

    As future boiling water reactors (BWR), concepts of evolutional ABWR (ABWR-IER) and natural circulation BWR (JSBWR) have been investigated in order to reduce their construction cost and simplify their maintenance and inspection procedures. One of the promised features of the design of the evolutional ABWR is to reduce the number of internal pumps and to remove the Motor Generation (MG) sets. These design changes may induce boiling transition in the fuel rods of reactor core during a pump trip transient due to the more rapid flow coastdown characteristics than these of the present design. In addition, the understanding of critical heat flux (CHF) is one important subject to grasp safety margin during the start-up for the natural circulation BWR and to establish the rational start-up procedure in which thermo-hydraulic instabilities can be suppressed. The present study is to clarify CHF characteristics under low velocity conditions. CHF measurements were conducted in a vertical upward annulus channel composed of an inner heated rod and an outer tube made of glass. CHF data were obtained repeatedly under the condition of stable inlet flow to examine statistically their reproducibility. The flow regime was investigated from flow observation and measurement of differential pressure fluctuation. The CHF data are correlated with the flow regime transition. It was clear from the obtained flow pattern and the CHF data that the CHF behavior could be classified into specified regions by the mass flux and inlet subcooling conditions. A CHF correlation was developed and agreed with other researchers' data within acceptable error. (author)

  8. Review of Critical Heat Flux Correlations for Upward Flow in a Vertical Thin Rectangular Channel

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Gil Sik; Chang, Soon Heung [Korea Advanced Institute of Science and Technology, Daejeon (Korea, Republic of)

    2014-05-15

    From the view point of safety, this type of fuel has higher resistance to earthquake and external impact. The cross section of coolant flow channel in the reactor core composed with the plate fuel is a thin rectangular shape. Thermal-hydraulic characteristics of this thin rectangular channel are different with those of general circular rod fuel bundle flow channel. Accordingly it could be thought that the CHF correlation in a thin rectangular channel is different with that in a circular channel, for which a large number of researches on CHF prediction have been carried out. The objective of this paper is to review previous researches on CHF in a thin rectangular channel, summarize the important conclusion and propose the new simple CHF correlation, which is based on the data set under high pressure and high flow rate condition. The researches on CHF in rectangular channel have been partially carried out according to the pressure, heated surface number, heated surface wettability effect, flow driving force and flow direction conditions. From the literature researches on CHF for upward flow in a vertical thin rectangular channel, some CHF prediction methods were reviewed and compared. There is no universal correlation which can predict CHF at all conditions, but generally, Katto empirical correlation is known to be useful at high pressure and high flow rate. The new simple correlation was developed from the restricted data set, the CHF prediction capacity of which is better than that of Katto. Even though the prediction consistency of the new simple correlation is lower, MAE and RMS error decreased quite. For the more development of the new simple CHF correlation, the more advanced regression analysis method and theoretical analysis should be studied in future.

  9. Review of Critical Heat Flux Correlations for Upward Flow in a Vertical Thin Rectangular Channel

    International Nuclear Information System (INIS)

    Choi, Gil Sik; Chang, Soon Heung

    2014-01-01

    From the view point of safety, this type of fuel has higher resistance to earthquake and external impact. The cross section of coolant flow channel in the reactor core composed with the plate fuel is a thin rectangular shape. Thermal-hydraulic characteristics of this thin rectangular channel are different with those of general circular rod fuel bundle flow channel. Accordingly it could be thought that the CHF correlation in a thin rectangular channel is different with that in a circular channel, for which a large number of researches on CHF prediction have been carried out. The objective of this paper is to review previous researches on CHF in a thin rectangular channel, summarize the important conclusion and propose the new simple CHF correlation, which is based on the data set under high pressure and high flow rate condition. The researches on CHF in rectangular channel have been partially carried out according to the pressure, heated surface number, heated surface wettability effect, flow driving force and flow direction conditions. From the literature researches on CHF for upward flow in a vertical thin rectangular channel, some CHF prediction methods were reviewed and compared. There is no universal correlation which can predict CHF at all conditions, but generally, Katto empirical correlation is known to be useful at high pressure and high flow rate. The new simple correlation was developed from the restricted data set, the CHF prediction capacity of which is better than that of Katto. Even though the prediction consistency of the new simple correlation is lower, MAE and RMS error decreased quite. For the more development of the new simple CHF correlation, the more advanced regression analysis method and theoretical analysis should be studied in future

  10. Solute transport with time-variable flow paths during upward and downward flux in a heterogeneous unsaturated porous medium

    Science.gov (United States)

    Cremer, Clemens; Neuweiler, Insa; Bechtold, Michel; Vanderborght, Jan

    2014-05-01

    To acquire knowledge of solute transport through the unsaturated zone in the shallow subsurface is decisive to assess groundwater quality, nutrient cycling or to plan remediation strategies. The shallow subsurface is characterized by structural heterogeneity and strongly influenced by atmospheric conditions. This leads to changing flow directions, strong temporal changes in saturation and heterogeneous water fluxes during infiltration and evaporation events. Recent studies (e.g. Lehmann and Or, 2009; Bechtold et al.,2011) demonstrated the importance of lateral flow and solute transport during evaporation conditions (upward flux). The heterogeneous structure in these studies was constructed using two types of sand with strong material contrasts and arranged in parallel with a vertical orientation. Lateral transport and redistribution of solute from coarse to fine media was observed deeper in the soil column and from fine to coarse close to the soil surface. However, if boundary conditions are reversed due to precipitation, the flow field is not necessarily reversed in the same manner, resulting in entirely different transport patterns for downward and upward flow. Therefore, considering net-flow rates alone is misleading when describing transport under those conditions. In this contribution we analyze transport of a solute in the shallow subsurface to assess effects resulting from the temporal change of heterogeneous soil structures due to dynamic flow conditions. Two-dimensional numerical simulations of unsaturated flow and transport are conducted using a coupled finite volume and random walk particle tracking algorithm to quantify solute transport and leaching rates. Following previous studies (Lehmann and Or, 2009; Bechtold et al., 2011), the chosen domain is composed of two materials, coarse and fine sand, arranged in parallel with a vertical orientation. Hence, one sharp interface of strong material heterogeneity is induced. During evaporation both sands are

  11. Dryout-type critical heat flux in vertical upward annular flow: effects of entrainment rate, initial entrained fraction and diameter

    Science.gov (United States)

    Wu, Zan; Wadekar, Vishwas; Wang, Chenglong; Sunden, Bengt

    2018-01-01

    This study aims to reveal the effects of liquid entrainment, initial entrained fraction and tube diameter on liquid film dryout in vertical upward annular flow for flow boiling. Entrainment and deposition rates of droplets were included in mass conservation equations to estimate the local liquid film mass flux in annular flow, and the critical vapor quality at dryout conditions. Different entrainment rate correlations were evaluated using flow boiling data of water and organic liquids including n-pentane, iso-octane and R134a. Effect of the initial entrained fraction (IEF) at the churn-to-annular flow transition was also investigated. A transitional Boiling number was proposed to separate the IEF-sensitive region at high Boiling numbers and the IEF-insensitive region at low Boiling numbers. Besides, the diameter effect on dryout vapor quality was studied. The dryout vapor quality increases with decreasing tube diameter. It needs to be pointed out that the dryout characteristics of submillimeter channels might be different because of different mechanisms of dryout, i.e., drying of liquid film underneath long vapor slugs and flow boiling instabilities.

  12. Heat transfer to sub- and supercritical water flowing upward in a vertical tube at low mass fluxes: numerical analysis and experimental validation

    NARCIS (Netherlands)

    Odu, Samuel Obarinu; Koster, P.; van der Ham, Aloysius G.J.; van der Hoef, Martin Anton; Kersten, Sascha R.A.

    2016-01-01

    Heat transfer to supercritical water (SCW) flowing upward in a vertical heated tube at low mass fluxes (G ≤ 20 kg/m2 s) has been numerically investigated in COMSOL Multiphysics and validated with experimental data. The turbulence models, essential to describing local turbulence, in COMSOL have been

  13. Prediction of the critical heat flux for saturated upward flow boiling water in vertical narrow rectangular channels

    International Nuclear Information System (INIS)

    Choi, Gil Sik; Chang, Soon Heung; Jeong, Yong Hoon

    2016-01-01

    A study, on the theoretical method to predict the critical heat flux (CHF) of saturated upward flow boiling water in vertical narrow rectangular channels, has been conducted. For the assessment of this CHF prediction method, 608 experimental data were selected from the previous researches, in which the heated sections were uniformly heated from both wide surfaces under the high pressure condition over 41 bar. For this purpose, representative previous liquid film dryout (LFD) models for circular channels were reviewed by using 6058 points from the KAIST CHF data bank. This shows that it is reasonable to define the initial condition of quality and entrainment fraction at onset of annular flow (OAF) as the transition to annular flow regime and the equilibrium value, respectively, and the prediction error of the LFD model is dependent on the accuracy of the constitutive equations of droplet deposition and entrainment. In the modified Levy model, the CHF data are predicted with standard deviation (SD) of 14.0% and root mean square error (RMSE) of 14.1%. Meanwhile, in the present LFD model, which is based on the constitutive equations developed by Okawa et al., the entire data are calculated with SD of 17.1% and RMSE of 17.3%. Because of its qualitative prediction trend and universal calculation convergence, the present model was finally selected as the best LFD model to predict the CHF for narrow rectangular channels. For the assessment of the present LFD model for narrow rectangular channels, effective 284 data were selected. By using the present LFD model, these data are predicted with RMSE of 22.9% with the dryout criterion of zero-liquid film flow, but RMSE of 18.7% with rivulet formation model. This shows that the prediction error of the present LFD model for narrow rectangular channels is similar with that for circular channels.

  14. Flux

    DEFF Research Database (Denmark)

    Ravn, Ib

    . FLUX betegner en flyden eller strømmen, dvs. dynamik. Forstår man livet som proces og udvikling i stedet for som ting og mekanik, får man et andet billede af det gode liv end det, som den velkendte vestlige mekanicisme lægger op til. Dynamisk forstået indebærer det gode liv den bedst mulige...... kanalisering af den flux eller energi, der strømmer igennem os og giver sig til kende i vore daglige aktiviteter. Skal vores tanker, handlinger, arbejde, samvær og politiske liv organiseres efter stramme og faste regelsæt, uden slinger i valsen? Eller skal de tværtimod forløbe ganske uhindret af regler og bånd...

  15. 78 FR 18326 - Agency Information Collection Activities; Comment Request; Upward Bound and Upward Bound Math...

    Science.gov (United States)

    2013-03-26

    ...; Comment Request; Upward Bound and Upward Bound Math Science Annual Performance Report AGENCY: The Office... considered public records. Title of Collection: Upward Bound and Upward Bound Math Science Annual Performance...) and Upward Bound Math and Science (UBMS) Programs. The Department is requesting a new APR because of...

  16. Multivalent Fcγ-receptor engagement by a hexameric Fc-fusion protein triggers Fcγ-receptor internalisation and modulation of Fcγ-receptor functions.

    Science.gov (United States)

    Qureshi, O S; Rowley, T F; Junker, F; Peters, S J; Crilly, S; Compson, J; Eddleston, A; Björkelund, H; Greenslade, K; Parkinson, M; Davies, N L; Griffin, R; Pither, T L; Cain, K; Christodoulou, L; Staelens, L; Ward, E; Tibbitts, J; Kiessling, A; Smith, B; Brennan, F R; Malmqvist, M; Fallah-Arani, F; Humphreys, D P

    2017-12-06

    Engagement of Fcγ-receptors triggers a range of downstream signalling events resulting in a diverse array of immune functions. As a result, blockade of Fc-mediated function is an important strategy for the control of several autoimmune and inflammatory conditions. We have generated a hexameric-Fc fusion protein (hexameric-Fc) and tested the consequences of multi-valent Fcγ-receptor engagement in in vitro and in vivo systems. In vitro engagement of hexameric-Fc with FcγRs showed complex binding interactions that altered with receptor density and triggered the internalisation and degradation of Fcγ-receptors. This caused a disruption of Fc-binding and phagocytosis. In vivo, in a mouse ITP model we observed a short half-life of hexameric-Fc but were nevertheless able to observe inhibition of platelet phagocytosis several days after hexameric-Fc dosing. In cynomolgus monkeys, we again observed a short half-life, but were able to demonstrate effective FcγR blockade. These findings demonstrate the ability of multi-valent Fc-based therapeutics to interfere with FcγR function and a potential mechanism through which they could have a sustained effect; the internalisation and degradation of FcγRs.

  17. Does urban sprawl hold down upward mobility?

    Science.gov (United States)

    Ewing, R.; Hamidi, Shima; Grace, James B.; Wei, Y.

    2016-01-01

    Contrary to the general perception, the United States has a much more class-bound society than other wealthy countries. The chance of upward mobility for Americans is just half that of the citizens of the Denmark and many other European countries. In addition to other influences, the built environment may contribute to the low rate of upward mobility in the U.S. This study tests the relationship between urban sprawl and upward mobility for commuting zones in the U.S. We examine potential pathways through which sprawl may have an effect on mobility. We use structural equation modeling to account for both direct and indirect effects of sprawl on upward mobility. We find that upward mobility is significantly higher in compact areas than sprawling areas. The direct effect, which we attribute to better job accessibility in more compact commuting zones, is stronger than the indirect effects. Of the indirect effects, only one, through the mediating variable income segregation, is significant.

  18. Analysis of the Effects of the Bruton's tyrosine kinase (Btk) Inhibitor Ibrutinib on Monocyte Fcγ Receptor (FcγR) Function.

    Science.gov (United States)

    Ren, Li; Campbell, Amanda; Fang, Huiqing; Gautam, Shalini; Elavazhagan, Saranya; Fatehchand, Kavin; Mehta, Payal; Stiff, Andrew; Reader, Brenda F; Mo, Xiaokui; Byrd, John C; Carson, William E; Butchar, Jonathan P; Tridandapani, Susheela

    2016-02-05

    The irreversible Bruton's tyrosine kinase (Btk) inhibitor ibrutinib has shown efficacy against B-cell tumors such as chronic lymphocytic leukemia and B-cell non-Hodgkin lymphoma. Fcγ receptors (FcγR) on immune cells such as macrophages play an important role in tumor-specific antibody-mediated immune responses, but many such responses involve Btk. Here we tested the effects of ibrutinib on FcγR-mediated activities in monocytes. We found that ibrutinib did not affect monocyte FcγR-mediated phagocytosis, even at concentrations higher than those achieved physiologically, but suppressed FcγR-mediated cytokine production. We confirmed these findings in macrophages from Xid mice in which Btk signaling is defective. Because calcium flux is a major event downstream of Btk, we tested whether it was involved in phagocytosis. The results showed that blocking intracellular calcium flux decreased FcγR-mediated cytokine production but not phagocytosis. To verify this, we measured activation of the GTPase Rac, which is responsible for actin polymerization. Results showed that ibrutinib did not inhibit Rac activation, nor did the calcium chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid tetrakis(acetoxymethyl ester). We next asked whether the effect of ibrutinib on monocyte FcγR-mediated cytokine production could be rescued by IFNγ priming because NK cells produce IFNγ in response to antibody therapy. Pretreatment of monocytes with IFNγ abrogated the effects of ibrutinib on FcγR-mediated cytokine production, suggesting that IFNγ priming could overcome this Btk inhibition. Furthermore, in monocyte-natural killer cell co-cultures, ibrutinib did not inhibit FcγR-mediated cytokine production despite doing so in single cultures. These results suggest that combining ibrutinib with monoclonal antibody therapy could enhance chronic lymphocytic leukemia cell killing without affecting macrophage effector function. © 2016 by The American Society for Biochemistry

  19. Analysis of the Effects of the Bruton's tyrosine kinase (Btk) Inhibitor Ibrutinib on Monocyte Fcγ Receptor (FcγR) Function*

    Science.gov (United States)

    Ren, Li; Campbell, Amanda; Fang, Huiqing; Gautam, Shalini; Elavazhagan, Saranya; Fatehchand, Kavin; Mehta, Payal; Stiff, Andrew; Reader, Brenda F.; Mo, Xiaokui; Byrd, John C.; Carson, William E.; Butchar, Jonathan P.; Tridandapani, Susheela

    2016-01-01

    The irreversible Bruton's tyrosine kinase (Btk) inhibitor ibrutinib has shown efficacy against B-cell tumors such as chronic lymphocytic leukemia and B-cell non-Hodgkin lymphoma. Fcγ receptors (FcγR) on immune cells such as macrophages play an important role in tumor-specific antibody-mediated immune responses, but many such responses involve Btk. Here we tested the effects of ibrutinib on FcγR-mediated activities in monocytes. We found that ibrutinib did not affect monocyte FcγR-mediated phagocytosis, even at concentrations higher than those achieved physiologically, but suppressed FcγR-mediated cytokine production. We confirmed these findings in macrophages from Xid mice in which Btk signaling is defective. Because calcium flux is a major event downstream of Btk, we tested whether it was involved in phagocytosis. The results showed that blocking intracellular calcium flux decreased FcγR-mediated cytokine production but not phagocytosis. To verify this, we measured activation of the GTPase Rac, which is responsible for actin polymerization. Results showed that ibrutinib did not inhibit Rac activation, nor did the calcium chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid tetrakis(acetoxymethyl ester). We next asked whether the effect of ibrutinib on monocyte FcγR-mediated cytokine production could be rescued by IFNγ priming because NK cells produce IFNγ in response to antibody therapy. Pretreatment of monocytes with IFNγ abrogated the effects of ibrutinib on FcγR-mediated cytokine production, suggesting that IFNγ priming could overcome this Btk inhibition. Furthermore, in monocyte-natural killer cell co-cultures, ibrutinib did not inhibit FcγR-mediated cytokine production despite doing so in single cultures. These results suggest that combining ibrutinib with monoclonal antibody therapy could enhance chronic lymphocytic leukemia cell killing without affecting macrophage effector function. PMID:26627823

  20. Atmospheric neutrino oscillations from upward throughgoing muon multiple scattering in MACRO

    Energy Technology Data Exchange (ETDEWEB)

    Ambrosio, M.; Antolini, R.; Bakari, D.; Baldini, A.; Barbarino, G.C.; Barish, B.C.; Battistoni, G.; Becherini, Y.; Bellotti, R.; Bemporad, C.; Bernardini, P.; Bilokon, H.; Bloise, C.; Bower, C.; Brigida, M.; Bussino, S.; Cafagna, F.; Calicchio, M.; Campana, D.; Carboni, M.; Caruso, R.; Cecchini, S.; Cei, F.; Chiarella, V.; Chiarusi, T.; Choudhary, B.C.; Coutu, S.; Cozzi, M.; De Cataldo, G.; Dekhissi, H.; De Marzo, C.; De Mitri, I.; Derkaoui, J.; De Vincenzi, M.; Di Credico, A.; Favuzzi, C.; Forti, C.; Fusco, P.; Giacomelli, G.; Giannini, G.; Giglietto, N.; Giorgini, M.; Grassi, M.; Grillo, A.; Gustavino, C.; Habig, A.; Hanson, K.; Heinz, R.; Iarocci, E.; Katsavounidis, E.; Katsavounidis, I.; Kearns, E.; Kim, H.; Kumar, A.; Kyriazopoulou, S.; Lamanna, E.; Lane, C.; Levin, D.S.; Lipari, P.; Longo, M.J.; Loparco, F.; Maaroufi, F.; Mancarella, G.; Mandrioli, G.; Manzoor, S.; Margiotta, A.; Marini, A.; Martello, D.; Marzari-Chiesa, A.; Mazziotta, M.N.; Michael, D.G.; Mikheyev, S.; Monacelli, P.; Montaruli, T.; Monteno, M.; Mufson, S.; Musser, J.; Nicolo, D.; Nolty, R.; Orth, C.; Osteria, G.; Palamara, O.; Patera, V.; Patrizii, L.; Pazzi, R.; Peck, C.W.; Perrone, L.; Petrera, S.; Popa, V.; Raino, A.; Reynoldson, J.; Ronga, F.; Rrhioua, A.; Satriano, C.; Scapparone, E.; Scholberg, K.; Sciubba, A.; Serra, P.; Sioli, M.; Sirri, G.; Sitta, M.; Spinelli, P.; Spinetti, M.; Spurio, M.; Steinberg, R.; Stone, J.L.; Sulak, L.R.; Surdo, A.; Tarle, G.; Togo, V.; Vakili, M.; Walter, C.W.; Webb, R

    2003-07-24

    The energy of atmospheric neutrinos detected by MACRO was estimated using multiple Coulomb scattering of upward throughgoing muons. This analysis allows a test of atmospheric neutrino oscillations, relying on the distortion of the muon energy distribution. These results have been combined with those coming from the upward throughgoing muon angular distribution only. Both analyses are independent of the neutrino flux normalization and provide strong evidence, above the 4{sigma} level, in favour of neutrino oscillations.

  1. Cover Art: River's Edge: Downward, Outward, Upward

    Directory of Open Access Journals (Sweden)

    Jonee Kulman Brigham

    2017-10-01

    Full Text Available Artist's Statement for the cover art of IJPS volume 4, issue 3: River's Edge: Downward, Outward, Upward, 2015. Mixed Media: photograph, inkjet printed on presentation matte of colored pencil over photograph.

  2. HAL/S-FC compiler system specifications

    Science.gov (United States)

    1976-01-01

    This document specifies the informational interfaces within the HAL/S-FC compiler, and between the compiler and the external environment. This Compiler System Specification is for the HAL/S-FC compiler and its associated run time facilities which implement the full HAL/S language. The HAL/S-FC compiler is designed to operate stand-alone on any compatible IBM 360/370 computer and within the Software Development Laboratory (SDL) at NASA/JSC, Houston, Texas.

  3. Heat transfer characteristics of supercritical pressure waster in vertical upward annular channels

    International Nuclear Information System (INIS)

    Wang Han; Bi Qincheng; Yang Zhendong; Wu Gang

    2013-01-01

    Within the range of pressure from 23 to 28 MPa, mass flux from 350 to 1000 kg/(m 2 · s), and outside wall heat flux from 200 to 1000 kW/m 2 , experimental investigation was conducted on the heat transfer characteristics of supercritical pressure water in vertical upward annular channels. The effects of heat flux, pressure, mass flux and spiral spacer on heat transfer were analyzed, and two types of heat transfer deterioration occurred in the experiments were compared. The experimental results show that the heat transfer of water can be enhanced by increasing the mass flux or decreasing the wall heat flux. The effect of pressure on heat transfer is not uniform and depends on heat transfer form. It was found that the spiral spacer not only enhances the heat transfer of water, but also delays the heat transfer deterioration which occurs in high heat flux and low mass flux conditions. (authors)

  4. A Study of Upward Influence in Organizations.

    Science.gov (United States)

    Schilit, Warren K.; Locke, Edwin A.

    1982-01-01

    Researchers interviewed 83 subordinate employees and 70 supervisory employees to investigate the ways subordinates try to influence their supervisors. Supervisors and subordinates reported similar agents and methods of influence, causes of success, and outcomes of attempts at upward influence, but different causes of failure. (Author/RW)

  5. FcγRll: Characterisation of novel Fc receptor interactions and a new receptor form.

    OpenAIRE

    JESSICA CLAIRE ANANIA

    2018-01-01

    Leukocyte Fc receptors (FcR) bind to immunogloulins (Ig) to link the innate and humoral immune system to help balance the immune system and clear infections. We have characterised a novel FcR for IgG (FcγR) form, designated FcγRIIa3, which contains a 19 amino acid insert. This insert interacts with cytoskeletal structures allowing the receptor to be retained for longer periods of time at the cells surface upon activation, higher cell signalling which causes greater cellular activation. Theref...

  6. Engineering of Immunoglobulin Fc Heterodimers Using Yeast Surface-Displayed Combinatorial Fc Library Screening.

    Directory of Open Access Journals (Sweden)

    Hye-Ji Choi

    Full Text Available Immunoglobulin Fc heterodimers, which are useful scaffolds for the generation of bispecific antibodies, have been mostly generated through structure-based rational design methods that introduce asymmetric mutations into the CH3 homodimeric interface to favor heterodimeric Fc formation. Here, we report an approach to generate heterodimeric Fc variants through directed evolution combined with yeast surface display. We developed a combinatorial heterodimeric Fc library display system by mating two haploid yeast cell lines, one haploid cell line displayed an Fc chain library (displayed FcCH3A with mutations in one CH3 domain (CH3A on the yeast cell surface, and the other cell line secreted an Fc chain library (secreted FcCH3B with mutations in the other CH3 domain (CH3B. In the mated cells, secreted FcCH3B is displayed on the cell surface through heterodimerization with the displayed FcCH3A, the detection of which enabled us to screen the library for heterodimeric Fc variants. We constructed combinatorial heterodimeric Fc libraries with simultaneous mutations in the homodimer-favoring electrostatic interaction pairs K370-E357/S364 or D399-K392/K409 at the CH3 domain interface. High-throughput screening of the libraries using flow cytometry yielded heterodimeric Fc variants with heterodimer-favoring CH3 domain interface mutation pairs, some of them showed high heterodimerization yields (~80-90% with previously unidentified CH3 domain interface mutation pairs, such as hydrogen bonds and cation-π interactions. Our study provides a new approach for engineering Fc heterodimers that could be used to engineer other heterodimeric protein-protein interactions through directed evolution combined with yeast surface display.

  7. Are Millennials with Student Loans Upwardly Mobile?

    OpenAIRE

    Whitaker, Stephan

    2015-01-01

    Students have been amassing ever growing levels of debt to attend college. The situation has raised concerns about whether the debt is high enough that the benefits of borrowing—in terms of students’ future socioeconomic outcomes—are compromised. This Commentary investigates relationships between student debt, mobility, and upward social mobility. The findings suggest that student debts have not become so burdensome that they undo the advantages of higher skills. However, the advantages enjoy...

  8. Dicty_cDB: FC-AI04 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available FC (Link to library) FC-AI04 (Link to dictyBase) - - - Contig-U15121-1 FC-AI04E (Li...nk to Original site) - - - - - - FC-AI04E 772 Show FC-AI04 Library FC (Link to library) Clone ID FC-AI04 (Li.../dictycdb.biol.tsukuba.ac.jp/CSM/FC/FC-AI/FC-AI04Q.Seq.d/ Representative seq. ID FC-AI...04E (Link to Original site) Representative DNA sequence >FC-AI04 (FC-AI04Q) /CSM/FC/FC-AI/FC-AI04Q.Seq....qvnkhqqvvtktvsd vlvphqvhnqvfphipqqmtlvnkhqpvvtktvsdvlvphqvhnqvfphtpqlkiqvylq vfqvvvvtiisai

  9. Dicty_cDB: FC-AI10 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available FC (Link to library) FC-AI10 (Link to dictyBase) - - - Contig-U16270-1 FC-AI10F (Li...nk to Original site) FC-AI10F 405 - - - - - - Show FC-AI10 Library FC (Link to library) Clone ID FC-AI10 (Li.../dictycdb.biol.tsukuba.ac.jp/CSM/FC/FC-AI/FC-AI10Q.Seq.d/ Representative seq. ID FC-AI...10F (Link to Original site) Representative DNA sequence >FC-AI10 (FC-AI10Q) /CSM/FC/FC-AI/FC-AI10Q.Seq.... sequence RKKRKSDYTSFSTYIHKLLKQITPPTNAKSNEKGDRKFTISSKAMSVMNSFVHDIFDRIA TEASGLAKKKKRQTLHSRDIQVAVRIILTGELAXHAI

  10. Dicty_cDB: FC-AI23 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available FC (Link to library) FC-AI23 (Link to dictyBase) - - - Contig-U15308-1 FC-AI23Z (Li...nk to Original site) - - FC-AI23Z 603 - - - - Show FC-AI23 Library FC (Link to library) Clone ID FC-AI23 (Li.../dictycdb.biol.tsukuba.ac.jp/CSM/FC/FC-AI/FC-AI23Q.Seq.d/ Representative seq. ID FC-AI...23Z (Link to Original site) Representative DNA sequence >FC-AI23 (FC-AI23Q) /CSM/FC/FC-AI/FC-AI23Q.Seq....LNTLAKKNEQVVEGEILAKQLTGVTAEELSEFKACFSHFDKDN DNKLNRLEFSSCLKSIGDELTEEQLNQVISKIDTDGNGTISFEEFIDYMVSSRKGTDSVE STKAAFKVMAEDKDFITEAQIRAAI

  11. Dicty_cDB: FC-AI05 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available FC (Link to library) FC-AI05 (Link to dictyBase) - - - Contig-U15516-1 FC-AI05E (Li...nk to Original site) - - - - - - FC-AI05E 1189 Show FC-AI05 Library FC (Link to library) Clone ID FC-AI05 (L...//dictycdb.biol.tsukuba.ac.jp/CSM/FC/FC-AI/FC-AI05Q.Seq.d/ Representative seq. ID FC-AI...05E (Link to Original site) Representative DNA sequence >FC-AI05 (FC-AI05Q) /CSM/FC/FC-AI/FC-AI05Q.Seq...KIVGEASLKNKGKMSRVLAAKAALSARFD ALCEVSDTSYGIAYKGAVDRRAAAIEGREVRKSLNAVKPEKSGNVAKYDHTKSATTNTTR DVATKSSKESSIKQEKQ

  12. Dicty_cDB: FC-AI21 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available FC (Link to library) FC-AI21 (Link to dictyBase) - - - Contig-U16254-1 FC-AI21Z (Li...nk to Original site) - - FC-AI21Z 696 - - - - Show FC-AI21 Library FC (Link to library) Clone ID FC-AI21 (Li.../dictycdb.biol.tsukuba.ac.jp/CSM/FC/FC-AI/FC-AI21Q.Seq.d/ Representative seq. ID FC-AI...21Z (Link to Original site) Representative DNA sequence >FC-AI21 (FC-AI21Q) /CSM/FC/FC-AI/FC-AI21Q.Seq....YPGYMYTDLSTIYERAGRIQGRNGSITQI PILTMPNDDITHPIPDLTGYITEGQIFIDRQINNRQIYPPINVLPSLSRLMKSAI

  13. The neonatal Fc receptor, FcRn, as a target for drug delivery and therapy.

    Science.gov (United States)

    Sockolosky, Jonathan T; Szoka, Francis C

    2015-08-30

    Immunoglobulin G (IgG)-based drugs are arguably the most successful class of protein therapeutics due in part to their remarkably long blood circulation. This arises from IgG interaction with the neonatal Fc receptor, FcRn. FcRn is the central regulator of IgG and albumin homeostasis throughout life and is increasingly being recognized as an important player in autoimmune disease, mucosal immunity, and tumor immune surveillance. Various engineering approaches that hijack or disrupt the FcRn-mediated transport pathway have been devised to develop long-lasting and non-invasive protein therapeutics, protein subunit vaccines, and therapeutics for treatment of autoimmune and infectious disease. In this review, we highlight the diverse biological functions of FcRn, emerging therapeutic opportunities, as well as the associated challenges of targeting FcRn for drug delivery and disease therapy. Copyright © 2015 Elsevier B.V. All rights reserved.

  14. Dicty_cDB: FC-BR23 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available FC (Link to library) FC-BR23 (Link to dictyBase) - - - Contig-U15008-1 FC-BR23Z (Li...nk to Original site) - - FC-BR23Z 641 - - - - Show FC-BR23 Library FC (Link to library) Clone ID FC-BR23 (Li.../dictycdb.biol.tsukuba.ac.jp/CSM/FC/FC-BR/FC-BR23Q.Seq.d/ Representative seq. ID FC-BR2...3Z (Link to Original site) Representative DNA sequence >FC-BR23 (FC-BR23Q) /CSM/FC/FC-BR/FC-BR23Q.Seq....9 0.0 SLA211 (SLA211Q) /CSM/SL/SLA2-A/SLA211Q.Seq.d/ 1029 0.0 FC-BR23 (FC-BR23Q) /CSM/FC/FC-BR/FC-BR2

  15. Dicty_cDB: FC-BS11 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available FC (Link to library) FC-BS11 (Link to dictyBase) - - - Contig-U16517-1 FC-BS11Z (Li...nk to Original site) - - FC-BS11Z 683 - - - - Show FC-BS11 Library FC (Link to library) Clone ID FC-BS11 (Li.../dictycdb.biol.tsukuba.ac.jp/CSM/FC/FC-BS/FC-BS11Q.Seq.d/ Representative seq. ID FC-BS...11Z (Link to Original site) Representative DNA sequence >FC-BS11 (FC-BS11Q) /CSM/FC/FC-BS/FC-BS11Q.Seq....s producing significant alignments: (bits) Value FC-BS11 (FC-BS11Q) /CSM/FC/FC-BS/FC-BS

  16. Dicty_cDB: FC-BS09 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available FC (Link to library) FC-BS09 (Link to dictyBase) - - - Contig-U16215-1 FC-BS09Z (Li...nk to Original site) - - FC-BS09Z 626 - - - - Show FC-BS09 Library FC (Link to library) Clone ID FC-BS09 (Li.../dictycdb.biol.tsukuba.ac.jp/CSM/FC/FC-BS/FC-BS09Q.Seq.d/ Representative seq. ID FC-BS...09Z (Link to Original site) Representative DNA sequence >FC-BS09 (FC-BS09Q) /CSM/FC/FC-BS/FC-BS09Q.Seq....ignments: (bits) Value SSF360 (SSF360Q) /CSM/SS/SSF3-C/SSF360Q.Seq.d/ 854 0.0 FC-BS09 (FC-BS09Q) /CSM/FC/FC-BS/FC-BS

  17. Dicty_cDB: FC-BS10 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available FC (Link to library) FC-BS10 (Link to dictyBase) - - - Contig-U16283-1 FC-BS10Z (Li...nk to Original site) - - FC-BS10Z 720 - - - - Show FC-BS10 Library FC (Link to library) Clone ID FC-BS10 (Li.../dictycdb.biol.tsukuba.ac.jp/CSM/FC/FC-BS/FC-BS10Q.Seq.d/ Representative seq. ID FC-BS...10Z (Link to Original site) Representative DNA sequence >FC-BS10 (FC-BS10Q) /CSM/FC/FC-BS/FC-BS10Q.Seq....E Sequences producing significant alignments: (bits) Value FC-BS10 (FC-BS10Q) /CSM/FC/FC-BS/FC-BS10Q.Seq.d/

  18. Dicty_cDB: FC-BS21 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available FC (Link to library) FC-BS21 (Link to dictyBase) - - - Contig-U15764-1 FC-BS21Z (Li...nk to Original site) - - FC-BS21Z 723 - - - - Show FC-BS21 Library FC (Link to library) Clone ID FC-BS21 (Li.../dictycdb.biol.tsukuba.ac.jp/CSM/FC/FC-BS/FC-BS21Q.Seq.d/ Representative seq. ID FC-BS...21Z (Link to Original site) Representative DNA sequence >FC-BS21 (FC-BS21Q) /CSM/FC/FC-BS/FC-BS21Q.Seq.... Score E Sequences producing significant alignments: (bits) Value FC-BS21 (FC-BS21Q) /CSM/FC/FC-BS/FC-BS21Q.

  19. Dicty_cDB: FC-BS19 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available FC (Link to library) FC-BS19 (Link to dictyBase) - - - Contig-U16583-1 FC-BS19E (Li...nk to Original site) - - - - - - FC-BS19E 604 Show FC-BS19 Library FC (Link to library) Clone ID FC-BS19 (Li.../dictycdb.biol.tsukuba.ac.jp/CSM/FC/FC-BS/FC-BS19Q.Seq.d/ Representative seq. ID FC-BS...19E (Link to Original site) Representative DNA sequence >FC-BS19 (FC-BS19Q) /CSM/FC/FC-BS/FC-BS19Q.Seq....E Sequences producing significant alignments: (bits) Value FC-BS19 (FC-BS19Q) /CSM/FC/FC-BS/FC-BS19Q.Seq.d/

  20. Dicty_cDB: FC-AI01 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available FC (Link to library) FC-AI01 (Link to dictyBase) - - - Contig-U15592-1 FC-AI01E (Li...nk to Original site) - - - - - - FC-AI01E 307 Show FC-AI01 Library FC (Link to library) Clone ID FC-AI01 (Li.../dictycdb.biol.tsukuba.ac.jp/CSM/FC/FC-AI/FC-AI01Q.Seq.d/ Representative seq. ID FC-AI...01E (Link to Original site) Representative DNA sequence >FC-AI01 (FC-AI01Q) /CSM/FC/FC-AI/FC-AI01Q.Seq....uences producing significant alignments: (bits) Value FC-AI01 (FC-AI01Q) /CSM/FC/FC-AI/FC-AI01Q.Seq.d/ 68 8e

  1. Dicty_cDB: FC-AI13 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available FC (Link to library) FC-AI13 (Link to dictyBase) - - - Contig-U16263-1 FC-AI13F (Li...nk to Original site) FC-AI13F 507 - - - - - - Show FC-AI13 Library FC (Link to library) Clone ID FC-AI13 (Li.../dictycdb.biol.tsukuba.ac.jp/CSM/FC/FC-AI/FC-AI13Q.Seq.d/ Representative seq. ID FC-AI...13F (Link to Original site) Representative DNA sequence >FC-AI13 (FC-AI13Q) /CSM/FC/FC-AI/FC-AI13Q.Seq....nificant alignments: (bits) Value FC-AI13 (FC-AI13Q) /CSM/FC/FC-AI/FC-AI13Q.Seq.d/ 963 0.0 VSA730 (VSA730Q)

  2. Human FcγRIIA induces anaphylactic and allergic reactions.

    Science.gov (United States)

    Jönsson, Friederike; Mancardi, David A; Zhao, Wei; Kita, Yoshihiro; Iannascoli, Bruno; Khun, Huot; van Rooijen, Nico; Shimizu, Takao; Schwartz, Lawrence B; Daëron, Marc; Bruhns, Pierre

    2012-03-15

    IgE and IgE receptors (FcεRI) are well-known inducers of allergy. We recently found in mice that active systemic anaphylaxis depends on IgG and IgG receptors (FcγRIIIA and FcγRIV) expressed by neutrophils, rather than on IgE and FcεRI expressed by mast cells and basophils. In humans, neutrophils, mast cells, basophils, and eosinophils do not express FcγRIIIA or FcγRIV, but FcγRIIA. We therefore investigated the possible role of FcγRIIA in allergy by generating novel FcγRIIA-transgenic mice, in which various models of allergic reactions induced by IgG could be studied. In mice, FcγRIIA was sufficient to trigger active and passive anaphylaxis, and airway inflammation in vivo. Blocking FcγRIIA in vivo abolished these reactions. We identified mast cells to be responsible for FcγRIIA-dependent passive cutaneous anaphylaxis, and monocytes/macrophages and neutrophils to be responsible for FcγRIIA-dependent passive systemic anaphylaxis. Supporting these findings, human mast cells, monocytes and neutrophils produced anaphylactogenic mediators after FcγRIIA engagement. IgG and FcγRIIA may therefore contribute to allergic and anaphylactic reactions in humans.

  3. Role of activatory Fc gamma RI and Fc gamma RIII and inhibitory Fc gamma RII in inflammation and cartilage destruction during experimental antigen-induced arthritis.

    NARCIS (Netherlands)

    Lent, P.L.E.M. van; Nabbe, K.C.A.M.; Blom, A.B.; Holthuysen, A.E.M.; Sloetjes, A.W.; Putte, L.B.A. van de; Verbeek, S.; Berg, W.B. van den

    2001-01-01

    IgG-containing immune complexes, which are found in most RA joints, communicate with hematopoietic cells using three classes of Fc receptors(Fc gamma RI, -II, -III). In a previous study we found that if a chronic T-cell-mediated antigen-induced arthritis (AIA) was elicited in knee joints of FcR

  4. Rapid polyclonal desensitization with antibodies to IgE and FcεRIα.

    Science.gov (United States)

    Khodoun, Marat V; Kucuk, Zeynep Yesim; Strait, Richard T; Krishnamurthy, Durga; Janek, Kevin; Lewkowich, Ian; Morris, Suzanne C; Finkelman, Fred D

    2013-06-01

    Rapid desensitization, a procedure in which persons allergic to an antigen are treated at short intervals with increasing doses of that antigen until they tolerate a large dose, is an effective, but risky, way to induce temporary tolerance. We wanted to determine whether this approach can be adapted to suppress all IgE-mediated allergies in mice by injecting serially increasing doses of monoclonal antibodies (mAbs) to IgE or FcεRIα. Active and passive models of antigen- and anti-IgE mAb-induced IgE-mediated anaphylaxis were used. Mice were desensitized with serially increasing doses of anti-IgE mAb, anti-FcεRIα mAb, or antigen. Development of shock (hypothermia), histamine and mast cell protease release, cytokine secretion, calcium flux, and changes in cell number and FcεRI and IgE expression were evaluated. Rapid desensitization with anti-IgE mAb suppressed IgE-mediated immediate hypersensitivity; however, some mice developed mild anaphylaxis during desensitization. Rapid desensitization with anti-FcεRIα mAb that only binds FcεRI that is not occupied by IgE suppressed both active and passive IgE-mediated anaphylaxis without inducing disease. It quickly, but temporarily, suppressed IgE-mediated anaphylaxis by decreasing mast cell signaling through FcεRI, then slowly induced longer lasting mast cell unresponsiveness by removing membrane FcεRI. Rapid desensitization with anti-FcεRIα mAb was safer and longer lasting than rapid desensitization with antigen. A rapid desensitization approach with anti-FcεRIα mAb safely desensitizes mice to IgE-mediated anaphylaxis by inducing mast cell anergy and later removing all mast cell IgE. Rapid desensitization with an anti-human FcεRIα mAb may be able to prevent human IgE-mediated anaphylaxis. Copyright © 2013 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

  5. Fc-fusion Proteins in Therapy: An Updated View.

    Science.gov (United States)

    Jafari, Reza; Zolbanin, Naime M; Rafatpanah, Houshang; Majidi, Jafar; Kazemi, Tohid

    2017-01-01

    Fc-fusion proteins are composed of Fc region of IgG antibody (Hinge-CH2-CH3) and a desired linked protein. Fc region of Fc-fusion proteins can bind to neonatal Fc receptor (FcRn) thereby rescuing it from degradation. The first therapeutic Fc-fusion protein was introduced for the treatment of AIDS. The molecular designing is the first stage in production of Fc-fusion proteins. The amino acid residues in the Fc region and linked protein are very important in the bioactivity and affinity of the fusion proteins. Although, therapeutic monoclonal antibodies are the top selling biologics but the application of therapeutic Fc-fusion proteins in clinic is in progress and among these medications Etanercept is the most effective in therapy. At present, eleven Fc-fusion proteins have been approved by FDA. There are novel Fc-fusion proteins which are in pre-clinical and clinical development. In this article, we review the molecular and biological characteristics of Fc-fusion proteins and then further discuss the features of novel therapeutic Fc-fusion proteins. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  6. Revisiting Field Capacity (FC: variation of definition of FC and its estimation from pedotransfer functions

    Directory of Open Access Journals (Sweden)

    Theophilo Benedicto Ottoni Filho

    2014-12-01

    Full Text Available Taking into account the nature of the hydrological processes involved in in situ measurement of Field Capacity (FC, this study proposes a variation of the definition of FC aiming not only at minimizing the inadequacies of its determination, but also at maintaining its original, practical meaning. Analysis of FC data for 22 Brazilian soils and additional FC data from the literature, all measured according to the proposed definition, which is based on a 48-h drainage time after infiltration by shallow ponding, indicates a weak dependency on the amount of infiltrated water, antecedent moisture level, soil morphology, and the level of the groundwater table, but a strong dependency on basic soil properties. The dependence on basic soil properties allowed determination of FC of the 22 soil profiles by pedotransfer functions (PTFs using the input variables usually adopted in prediction of soil water retention. Among the input variables, soil moisture content θ (6 kPa had the greatest impact. Indeed, a linear PTF based only on it resulted in an FC with a root mean squared residue less than 0.04 m³ m-3 for most soils individually. Such a PTF proved to be a better FC predictor than the traditional method of using moisture content at an arbitrary suction. Our FC data were compatible with an equivalent and broader USA database found in the literature, mainly for medium-texture soil samples. One reason for differences between FCs of the two data sets of fine-textured soils is due to their different drainage times. Thus, a standardized procedure for in situ determination of FC is recommended.

  7. Dicty_cDB: FC-BS14 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available FC (Link to library) FC-BS14 (Link to dictyBase) - - - Contig-U16399-1 FC-BS14E (Li...nk to Original site) - - - - - - FC-BS14E 534 Show FC-BS14 Library FC (Link to library) Clone ID FC-BS14 (Li.../dictycdb.biol.tsukuba.ac.jp/CSM/FC/FC-BS/FC-BS14Q.Seq.d/ Representative seq. ID FC-BS...14E (Link to Original site) Representative DNA sequence >FC-BS14 (FC-BS14Q) /CSM/FC/FC-BS/FC-BS14Q.Seq.... vs CSM-cDNA Score E Sequences producing significant alignments: (bits) Value FC-BS14 (FC-BS

  8. Dicty_cDB: FC-AI17 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available FC (Link to library) FC-AI17 (Link to dictyBase) - - - Contig-U15690-1 FC-AI17P (Li...nk to Original site) FC-AI17F 587 FC-AI17Z 626 FC-AI17P 1212 - - Show FC-AI17 Library FC (Link to library) Clone ID FC-AI...nal site URL http://dictycdb.biol.tsukuba.ac.jp/CSM/FC/FC-AI/FC-AI17Q.Seq.d/ Representative seq. ID FC-AI...17P (Link to Original site) Representative DNA sequence >FC-AI17 (FC-AI17Q) /CSM/FC/FC-AI/FC-AI...slated Amino Acid sequence ANIATVGDFLKADTVVPKMIITYNKRKQGTDYLKAVIGPILSNVIKQELNLELKPNLVYA AIISEQEIRTGEKSTLDRNV

  9. Dicty_cDB: FC-AI18 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available FC (Link to library) FC-AI18 (Link to dictyBase) - - - Contig-U15590-1 FC-AI18P (Li...nk to Original site) FC-AI18F 621 FC-AI18Z 703 FC-AI18P 1324 - - Show FC-AI18 Library FC (Link to library) Clone ID FC-AI...nal site URL http://dictycdb.biol.tsukuba.ac.jp/CSM/FC/FC-AI/FC-AI18Q.Seq.d/ Representative seq. ID FC-AI...18P (Link to Original site) Representative DNA sequence >FC-AI18 (FC-AI18Q) /CSM/FC/FC-AI/FC-AI...AVWPLIPGYERA DGEKQYPVAAMLCNFTKPTPTTPSLLTHDEVVTFFHEFGHVMHNMSTKVHYSMFSGTSVE RDFVECPSQLFEFWCWNKDVLVNKLSGHXKDHSKKLPTDLVERMIAAKNLNVAI

  10. Dicty_cDB: FC-AI03 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available FC (Link to library) FC-AI03 (Link to dictyBase) - - - Contig-U15833-1 FC-AI03P (Li...nk to Original site) FC-AI03F 690 FC-AI03Z 651 FC-AI03P 1341 - - Show FC-AI03 Library FC (Link to library) Clone ID FC-AI...nal site URL http://dictycdb.biol.tsukuba.ac.jp/CSM/FC/FC-AI/FC-AI03Q.Seq.d/ Representative seq. ID FC-AI...03P (Link to Original site) Representative DNA sequence >FC-AI03 (FC-AI03Q) /CSM/FC/FC-AI/FC-AI...li*l*ivtlskv*qswyqvfcslmrftcwi*nv fht*ivhwsqhwhql*flqpivaiv*skapitifnlhmaslwif*ivl*sfvpfhiitmk sfkfspfvpqlki

  11. UPWARD MOVEMENT OF PLUTONIUM TO SURFACE SEDIMENTS DURING AN 11-YEAR FIELD STUDY

    Energy Technology Data Exchange (ETDEWEB)

    Kaplan, D.; Beals, D.; Cadieux, J.; Halverson, J.

    2010-01-25

    An 11-y lysimeter study was established to monitor the movement of Pu through vadose zone sediments. Sediment Pu concentrations as a function of depth indicated that some Pu moved upward from the buried source material. Subsequent numerical modeling suggested that the upward movement was largely the result of invading grasses taking up the Pu and translocating it upward. The objective of this study was to determine if the Pu of surface sediments originated from atmosphere fallout or from the buried lysimeter source material (weapons-grade Pu), providing additional evidence that plants were involved in the upward migration of Pu. The {sup 240}Pu/{sup 239}Pu and {sup 242}Pu/{sup 239}Pu atomic fraction ratios of the lysimeter surface sediments, as determined by Thermal Ionization Mass Spectroscopy (TIMS), were 0.063 and 0.00045, respectively; consistent with the signatures of the weapons-grade Pu. Our numerical simulations indicate that because plants create a large water flux, small concentrations over multiple years may result in a measurable accumulation of Pu on the ground surface. These results may have implications on the conceptual model for calculating risk associated with long-term stewardship and monitored natural attenuation management of Pu contaminated subsurface and surface sediments.

  12. Experimental investigation of small diameter two-phase closed thermosyphons charged with water, FC-84, FC-77 and FC-3283

    International Nuclear Information System (INIS)

    Jouhara, Hussam; Robinson, Anthony J.

    2010-01-01

    An experimental investigation of the performance of thermosyphons charged with water as well as the dielectric heat transfer liquids FC-84, FC-77 and FC-3283 has been carried out. The copper thermosyphon was 200 mm long with an inner diameter of 6 mm, which can be considered quite small compared with the vast majority of thermosyphons reported in the open literature. The evaporator length was 40 mm and the condenser length was 60 mm which corresponds with what might be expected in compact heat exchangers. With water as the working fluid two fluid loadings were investigated, that being 0.6 ml and 1.8 ml, corresponding to approximately half filled and overfilled evaporator section in order to ensure combined pool boiling and thin film evaporation/boiling and pool boiling only conditions, respectively. For the Fluorinert TM liquids, only the higher fill volume was tested as the aim was to investigate pool boiling opposed to thin film evaporation. Generally, the water-charged thermosyphon evaporator and condenser heat transfer characteristics compared well with available predictive correlations and theories. The thermal performance of the water-charged thermosyphon also outperformed the other three working fluids in both the effective thermal resistance as well as maximum heat transport capabilities. Even so, FC-84, the lowest saturation temperature fluid tested, shows marginal improvement in the heat transfer at low operating temperatures. All of the tested Fluorinert TM liquids offer the advantage of being dielectric fluids, which may be better suited for sensitive electronics cooling applications and were all found to provide adequate thermal performance up to approximately 30-50 W after which liquid entrainment compromised their performance.

  13. Discussion on the tropospheric concentrations of FC21

    Energy Technology Data Exchange (ETDEWEB)

    Crescentini, G.; Mangani, F.; Mastrogiamcomo, A.R.; Cappiello, A.; Bruner, F.

    1986-01-01

    FC21 tropospheric mixing ratios measured in air samples collected at different locations in the world are presented. Results of a campaign carried out at two locations in the Sahara desert where FC21 and FC11 mixing ratios were simultaneously determined in 180 samples are also shown. Though scattered high values have been found, the average background concentration of FC21 ranged between 0 and 1 pptv. 9 references, 1 figure, 2 tables.

  14. Experimental detection of upward-going cosmic particles and consequences for correction of density radiography of volcanoes

    Science.gov (United States)

    Jourde, Kevin; Gibert, Dominique; Marteau, Jacques; de Bremond d'Ars, Jean; Gardien, Serge; Girerd, Claude; Ianigro, Jean-Christophe; Carbone, Daniele

    2014-05-01

    Muon tomography measures the flux of cosmic muons crossing geological bodies to determine their density. Three acquisitions with different sights of view were made at la soufrière de Guadeloupe. All of them show important density fluctuations and reveal the volcano phreatic system. The telescopes used to perform these measurements are exposed to noise fluxes with high intensities relative to the tiny flux of interest. We give experimental evidences ofa so far never described source of noise caused by a flux of upward-going particles. Data acquired on La soufrière of Guadeloupe and Mount Etna reveal that upward-going particles are detected only when the rear side of the telescope is exposed to a wide volume of atmosphere located below the altitude of the telescope and with a rock obstruction less than several tens of meters. Biases produced on density muon radiographies by upward-going fluxes are quantified and correction procedures are applied to radiographies of la soufrière.

  15. Dicty_cDB: FC-AI12 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available FC (Link to library) FC-AI12 (Link to dictyBase) - - - Contig-U15484-1 FC-AI12Z (Li...nk to Original site) - - FC-AI12Z 614 - - - - Show FC-AI12 Library FC (Link to library) Clone ID FC-AI12 (Li.../dictycdb.biol.tsukuba.ac.jp/CSM/FC/FC-AI/FC-AI12Q.Seq.d/ Representative seq. ID FC-AI...12Z (Link to Original site) Representative DNA sequence >FC-AI12 (FC-AI12Q) /CSM/FC/FC-AI/FC-AI12Q.Seq....EKIVRRI ELLDGITCYRNEKAKDEIVLTGNSLELLSQSCATIQLRSAIKYKDVRKFLDGIYVSERNV LESN*in*riys

  16. Dicty_cDB: FC-AI19 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available FC (Link to library) FC-AI19 (Link to dictyBase) - - - Contig-U15115-1 FC-AI19Z (Li...nk to Original site) - - FC-AI19Z 661 - - - - Show FC-AI19 Library FC (Link to library) Clone ID FC-AI19 (Li.../dictycdb.biol.tsukuba.ac.jp/CSM/FC/FC-AI/FC-AI19Q.Seq.d/ Representative seq. ID FC-AI...19Z (Link to Original site) Representative DNA sequence >FC-AI19 (FC-AI19Q) /CSM/FC/FC-AI/FC-AI19Q.Seq....lmrqswvkkiesi*lvl krrkkkknnkkkkkkkkkkklfn*lvnkkn*ik*kkllcnqkk Frame B: ---*ekaieilsklfsin*kfn**ysiiigkkstkyq

  17. Dicty_cDB: FC-AI14 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available FC (Link to library) FC-AI14 (Link to dictyBase) - - - Contig-U16280-1 FC-AI14Z (Li...nk to Original site) - - FC-AI14Z 671 - - - - Show FC-AI14 Library FC (Link to library) Clone ID FC-AI14 (Li.../dictycdb.biol.tsukuba.ac.jp/CSM/FC/FC-AI/FC-AI14Q.Seq.d/ Representative seq. ID FC-AI...14Z (Link to Original site) Representative DNA sequence >FC-AI14 (FC-AI14Q) /CSM/FC/FC-AI/FC-AI14Q.Seq....nqrllv*lvvlskklqllnsnqsfkfkkvq rmkknsvkntkn*rfvllt*nlkslkrmpksknsptkliifilkly Frame B: ---lkdl*krtphl*stcfhhptlcssrrfclwslnai

  18. Dicty_cDB: FC-AI15 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available FC (Link to library) FC-AI15 (Link to dictyBase) - G01730 DDB0214993 Contig-U15123-1 FC-AI...15E (Link to Original site) - - - - - - FC-AI15E 856 Show FC-AI15 Library FC (Link to library) Clone ID FC-AI...3-1 Original site URL http://dictycdb.biol.tsukuba.ac.jp/CSM/FC/FC-AI/FC-AI15Q.Se...q.d/ Representative seq. ID FC-AI15E (Link to Original site) Representative DNA sequence >FC-AI15 (FC-AI15Q) /CSM/FC/FC-AI/FC-AI...AAAAAAAATA sequence update 1996.12.24 Translated Amino Acid sequence kt*riyi*KMMIKYITIAILFIASLVKADLQFSLCPTCV

  19. Dicty_cDB: FC-AI24 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available FC (Link to library) FC-AI24 (Link to dictyBase) - - - - FC-AI24Z (Link to Original site) - - FC-AI...24Z 693 - - - - Show FC-AI24 Library FC (Link to library) Clone ID FC-AI24 (Link to dictyBas...e) Atlas ID - NBRP ID - dictyBase ID - Link to Contig - Original site URL http://dictycdb.biol.tsukuba.ac.jp/CSM/FC/FC-AI/FC-AI...24Q.Seq.d/ Representative seq. ID FC-AI24Z (Link to Original s...ite) Representative DNA sequence >FC-AI24 (FC-AI24Q) /CSM/FC/FC-AI/FC-AI24Q.Seq.d/ XXXXXXXXXXAAATTAGAAAACAAA

  20. Dicty_cDB: FC-AI06 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available FC (Link to library) FC-AI06 (Link to dictyBase) - - - Contig-U16465-1 FC-AI06E (Li...nk to Original site) - - - - - - FC-AI06E 1138 Show FC-AI06 Library FC (Link to library) Clone ID FC-AI06 (L...//dictycdb.biol.tsukuba.ac.jp/CSM/FC/FC-AI/FC-AI06Q.Seq.d/ Representative seq. ID FC-AI...06E (Link to Original site) Representative DNA sequence >FC-AI06 (FC-AI06Q) /CSM/FC/FC-AI/FC-AI06Q.Seq...FGRGIDIERVNVVINYDMAESADTYLHRVGRAGRFGTK GLAISFVPSKEDPVLEQVQSKFVVSIKELVATPDPSTYMSG*kkkkkkkknlfvlksikk k*kkk*in

  1. Dicty_cDB: FC-AI09 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available FC (Link to library) FC-AI09 (Link to dictyBase) - - - Contig-U16149-1 FC-AI09Z (Li...nk to Original site) - - FC-AI09Z 591 - - - - Show FC-AI09 Library FC (Link to library) Clone ID FC-AI09 (Li.../dictycdb.biol.tsukuba.ac.jp/CSM/FC/FC-AI/FC-AI09Q.Seq.d/ Representative seq. ID FC-AI...09Z (Link to Original site) Representative DNA sequence >FC-AI09 (FC-AI09Q) /CSM/FC/FC-AI/FC-AI09Q.Seq....*tkl ik*ilifykiknnkkkkkk Frame B: ---gt*kvpeflailfkrmasrsvlwy*rcltkakkglkapqtltik

  2. Field flow fractionation for assessing neonatal Fc receptor and Fcγ receptor binding to monoclonal antibodies in solution.

    Science.gov (United States)

    Pollastrini, Joey; Dillon, Thomas M; Bondarenko, Pavel; Chou, Robert Y-T

    2011-07-01

    Analysis of the strength and stoichiometry of immunoglobulin G (IgG) binding to neonatal Fc receptor (FcRn) and Fcγ receptor (FcγR) is important for evaluating the pharmacokinetics and effector functions of therapeutic monoclonal antibody (mAb) products, respectively. The current standard for assessing FcγR and FcRn binding is composed of cell-based and surface plasmon resonance (SPR) assays. In this work, asymmetrical flow field flow fractionation (AF4) was evaluated to establish the true stoichiometry of IgG binding in solution. AF4 and liquid chromatography-mass spectrometry (LC-MS) were applied to directly observe IgG/FcγR and IgG/FcRn complexes, which were not observed using nonequilibrium size exclusion chromatography (SEC) analysis. Human serum albumin (HSA), an abundant component of human blood and capable of binding FcRn, was studied in combination with FcRn and IgG. AF4 demonstrated that the majority of large complexes of IgG/FcRn/HSA were at an approximate 1:2:1 molar ratio. In addition, affinity measurements of the complex were performed in the sub-micromolar affinity range. A significant decrease in binding was detected for IgG molecules with increased oxidation in the Fc region. AF4 was useful in detecting weak binding between full-length IgG/Fc fragments and Fc receptors and the effect of chemical modifications on binding. AF4 is a useful technique in the assessment of mAb product quality attributes. Copyright © 2011 Elsevier Inc. All rights reserved.

  3. Submarine Upward Looking Sonar Ice Draft Profile Data and Statistics

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This data set consists of upward looking sonar draft data collected by submarines in the Arctic Ocean. It includes data from both U.S. Navy and Royal Navy...

  4. Dicty_cDB: FC-BR21 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available FC (Link to library) FC-BR21 (Link to dictyBase) - - - Contig-U15384-1 | Contig-U16443-1 FC-BR2...1P (Link to Original site) FC-BR21F 551 FC-BR21Z 122 FC-BR21P 673 - - Show FC-BR21 Library FC (L...ink to library) Clone ID FC-BR21 (Link to dictyBase) Atlas ID - NBRP ID - dictyBase ID - Link to Contig Cont...ig-U15384-1 | Contig-U16443-1 Original site URL http://dictycdb.biol.tsukuba.ac.jp/CSM/FC/FC-BR/FC-BR2...1Q.Seq.d/ Representative seq. ID FC-BR21P (Link to Original site) Representative DNA sequence >FC-BR21 (FC-BR2

  5. Dicty_cDB: FC-AI07 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available FC (Link to library) FC-AI07 (Link to dictyBase) - - - Contig-U15296-1 | Contig-U15756-1 FC-AI...07P (Link to Original site) FC-AI07F 580 FC-AI07Z 723 FC-AI07P 1303 - - Show FC-AI07 Library FC (...Link to library) Clone ID FC-AI07 (Link to dictyBase) Atlas ID - NBRP ID - dictyBase ID - Link to Contig Con...tig-U15296-1 | Contig-U15756-1 Original site URL http://dictycdb.biol.tsukuba.ac.jp/CSM/FC/FC-AI/FC-AI...07Q.Seq.d/ Representative seq. ID FC-AI07P (Link to Original site) Representative DNA sequence >FC-AI07 (FC-AI

  6. Dicty_cDB: FC-AI22 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available FC (Link to library) FC-AI22 (Link to dictyBase) - - - Contig-U15369-1 | Contig-U15732-1 FC-AI...22P (Link to Original site) FC-AI22F 583 FC-AI22Z 683 FC-AI22P 1266 - - Show FC-AI22 Library FC (...Link to library) Clone ID FC-AI22 (Link to dictyBase) Atlas ID - NBRP ID - dictyBase ID - Link to Contig Con...tig-U15369-1 | Contig-U15732-1 Original site URL http://dictycdb.biol.tsukuba.ac.jp/CSM/FC/FC-AI/FC-AI...22Q.Seq.d/ Representative seq. ID FC-AI22P (Link to Original site) Representative DNA sequence >FC-AI22 (FC-AI

  7. Dicty_cDB: FC-AI08 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available FC (Link to library) FC-AI08 (Link to dictyBase) - G01729 DDB0233148 Contig-U14939-1 FC-AI...08P (Link to Original site) FC-AI08F 654 FC-AI08Z 563 FC-AI08P 1217 - - Show FC-AI08 Library FC (Link... to library) Clone ID FC-AI08 (Link to dictyBase) Atlas ID - NBRP ID G01729 dictyBase ID DDB0233148 Link to ...Contig Contig-U14939-1 Original site URL http://dictycdb.biol.tsukuba.ac.jp/CSM/FC/FC-AI/FC-AI...08Q.Seq.d/ Representative seq. ID FC-AI08P (Link to Original site) Representative DNA sequence >FC-AI08 (FC-AI

  8. Reversal of Flux Closure States in Cobalt Nanoparticle Rings With Coaxial Magnetic Pulses

    DEFF Research Database (Denmark)

    Kasama, T; Dunin-Borkowski, Rafal E.; Scheinfein, MR

    2008-01-01

    Bistable flux closure (FC) states in Co nanoparticle rings can be switched reversibly by applying a coaxial magnetic field (H-z). The FC switching phenomena can be reproduced by micromagnetics simulations, which also reveal novel magnetic states at intermediate applied field strengths.......Bistable flux closure (FC) states in Co nanoparticle rings can be switched reversibly by applying a coaxial magnetic field (H-z). The FC switching phenomena can be reproduced by micromagnetics simulations, which also reveal novel magnetic states at intermediate applied field strengths....

  9. Optimal football strategies: AC Milan versus FC Barcelona

    OpenAIRE

    Papahristodoulou, Christos

    2012-01-01

    In a recent UEFA Champions League game between AC Milan and FC Barcelona, played in Italy (final score 2-3), the collected match statistics, classified into four offensive and two defensive strategies, were in favour of FC Barcelona (by 13 versus 8 points). The aim of this paper is to examine to what extent the optimal game strategies derived from some deterministic, possibilistic, stochastic and fuzzy LP models would improve the payoff of AC Milan at the cost of FC Barcelona.

  10. Evaluation of upward migration around a deep injection well

    International Nuclear Information System (INIS)

    Chia, Yeeping; Chiu, J.

    1994-01-01

    The long-term containment of injected wastes in the deep subsurface is expected to be achieved under suitable geologic and hydrologic conditions and by the use of competent engineering practices. Field experiences, however, indicate that waste containment may be affected by hydrologic conduits around the injection well. To assess the potential effects of these conduits, upward migration of injected waste is examined through the use of numerical models under various conditions. Test results indicate that without any preferential hydrologic conduits, most of the injected waste moves laterally in the injection interval, whereas only a small amount of waste migrates upward into the containment interval. When vertical fractures in the disturbed zone or defects in the cement seal around the wellbore exist, the contaminant can move rapidly upward along these conduits to an overlying aquifer, from which it migrates in the lateral direction. The contamination of the overlying aquifer that results from the upward migration of injected waste through these conduits cannot be impeded by a thick, low-permeability containment interval. However, when permeable interbeds exist within the containment interval, a significant portion of the waste migrating upward can be diverted laterally before reaching the overlying aquifer. The front of built-up pressure can reach the aquifer or permeable interbed immediately overlying the injection interval through the preferential hydrologic conduits shortly after the injection starts, but it cannot move farther upward because of pressure dissipation in the permeable formation. This study suggests that the injected waste has the potential to migrate upward into overlying formations through preferential migration conduits around the wellbore

  11. A Heat Transfer Correlation in a Vertical Upward Flow of CO2 at Supercritical Pressures

    International Nuclear Information System (INIS)

    Kim, Hyung Rae; Bae, Yoon Yeong; Song, Jin Ho; Kim, Hwan Yeol

    2006-01-01

    Heat transfer data has been collected in the heat transfer test loop, named SPHINX (Supercritical Pressure Heat Transfer Investigation for NeXt generation), in KAERI. The facility primarily aims at the generation of heat transfer data in the flow conditions and geometries relevant to SCWR (SuperCritical Water-cooled Reactor). The produced data will aid the thermohydraulic design of a reactor core. The loop uses carbon dioxide, and later the results will be scaled to the water flows. The heat transfer data has been collected for a vertical upward flow in a circular tube with varying mass fluxes, heat fluxes, and operating pressures. The results are compared with the existing correlations and a new correlation is proposed by fine-tuning the one of the existing correlations

  12. A self-consistent upward leader propagation model

    International Nuclear Information System (INIS)

    Becerra, Marley; Cooray, Vernon

    2006-01-01

    The knowledge of the initiation and propagation of an upward moving connecting leader in the presence of a downward moving lightning stepped leader is a must in the determination of the lateral attraction distance of a lightning flash by any grounded structure. Even though different models that simulate this phenomenon are available in the literature, they do not take into account the latest developments in the physics of leader discharges. The leader model proposed here simulates the advancement of positive upward leaders by appealing to the presently understood physics of that process. The model properly simulates the upward continuous progression of the positive connecting leaders from its inception to the final connection with the downward stepped leader (final jump). Thus, the main physical properties of upward leaders, namely the charge per unit length, the injected current, the channel gradient and the leader velocity are self-consistently obtained. The obtained results are compared with an altitude triggered lightning experiment and there is good agreement between the model predictions and the measured leader current and the experimentally inferred spatial and temporal location of the final jump. It is also found that the usual assumption of constant charge per unit length, based on laboratory experiments, is not valid for lightning upward connecting leaders

  13. Optimization on Fc for Improvement of Stability and Aggregation Resistance.

    Science.gov (United States)

    Chen, Xiaobo; Zeng, Fang; Huang, Tao; Cheng, Liang; Liu, Huan; Gong, Rui

    2016-01-01

    Fc-based therapeutics including therapeutic full-size monoclonal antibodies (mAbs) and Fcfusion proteins represent fastest-growing market in biopharmaceutical industrial. However, one major challenge during development of Fc-based therapeutics is how to maintain their efficacy in clinic use. Many factors may lead to failure in final marketing. For example, the stability and aggregation resistance might not be high enough for bearing the disadvantages during fermentation, purification, formulation, storage, shipment and other steps in manufacture and sale. Low stability and high aggregation tendency lead to decreased bioactivity and increased risk of immunogenicity resulting in serious side effect. Because Fc is one of the major parts in monoclonal antibodies and Fc-fusion proteins, engineering of Fc to increase its stability and reduce or eliminate aggregation due to incorrect association are of great importance and could further extend the potential of Fc-based therapeutics. Lots of studies focus on Fc optimization for better physical and chemical characteristics and function by structured-based computer-aid rational design, high-throughput screening expression system selection and other methods. The identification of optimized Fc mutants increases the clinic potential of currently existed therapeutics mAbs and Fc-fusion proteins, and accelerates the development of new Fc-based therapeutics. Here we provide an overview of the related field, and discuss recent advances and future directions in optimization of Fc-based therapeutics with modified stability and aggregation resistance. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  14. Thermal decomposition of FC(O)OCH3 and FC(O)OCH2CH3.

    Science.gov (United States)

    Berasategui, M; Argüello, G A; Burgos Paci, M A

    2018-05-09

    The thermal decomposition of methyl and ethyl formates has been extensively studied due to their importance in the oxidation of several fuels, pesticidal properties and their presence in interstellar space. We hitherto present the study of the thermal decomposition of methyl and ethyl fluoroformates, which could help in the elucidation of the reaction mechanisms. The reaction mechanisms were studied using FTIR spectroscopy in the temperature range of 453-733 K in the presence of different pressures of N2 as bath gas. For FC(O)OCH3 two different channels were observed; the unimolecular decomposition which is favored at higher temperatures and has a rate constant kFC(O)OCH3 = (5.3 ± 0.5) × 1015 exp[-(246 ± 10 kJ mol-1/RT)] (in units of s-1) and a bimolecular channel with a rate constant kFC(O)OCH3 = (1.6 ± 0.5) × 1011 exp[-(148 ± 10 kJ mol-1/RT)] (in units of s-1 (mol L)-1). However for ethyl formate, only direct elimination of CO2, HF and ethylene operates. The rate constants of the homogeneous first-order process fit the Arrhenius equation kFC(O)OCH2CH3 = (2.06 ± 0.09) × 1013 exp[-(169 ± 6 kJ mol-1/RT)] (in units of s-1). The difference between the mechanisms of the two fluoroformates relies on the stabilization of a six-centered transition state that only exists for ethyl formate. First principles calculations for the different channels were carried out to understand the dynamics of the decomposition.

  15. Upwards Intensifiers in the English, German and Croatian Language

    Directory of Open Access Journals (Sweden)

    Anita Pavić Pintarić

    2014-12-01

    Full Text Available This paper investigates the upwards intensifiers (adverbs of intensifying in the English, German and Croatian language. Intensity as an important human cognitive category, and language expressivity is differently treated in grammars and dictionaries of all three languages, especially with respect to different degrees of intensity. In this paper we argue that it is possible to model a typology of upwards adverb intensifiers in the three languages, according to their morphosyntactic and semantic aspects. When it comes to intensifiers, it is necessary to describe which collocates are modified by intensifiers and which semantic fields the collocates belong to. The results of the corpus analysis based on Harry Potter novels show that all the three languages express the category of the upwards intensity in the same way: the number of intensifiers is similar, the collocates mostly belong to the same semantic fields and word classes, they have similar syntactic functions.

  16. Construction of a bimolecular fluorescence complementation (BiFC ...

    African Journals Online (AJOL)

    Protein–protein interactions are essential for signal transduction in cells. Bimolecular fluorescence complementation (BiFC) is a novel technology that utilises green fluorescent proteins to visualize protein–protein interactions and subcellular protein localisation. BiFC based on pSATN vectors are a good system for ...

  17. Two upward lightning at the Eagle Nest tower

    OpenAIRE

    Montañá Puig, Juan; Van der Velde, Oscar Arnoud; Romero Durán, David; March Nomen, Víctor; Solà de Las Fuentes, Gloria; Pineda Ruegg, Nicolau; Soula, Serge; Hermoso Alameda, Blas

    2012-01-01

    A new instrument composed by a high speed camera, two high energy detectors, a E-field antenna and a VHF antenna were installed at the Eagle Nest tower (northeast of Spain) during summer 2011. With this equipment several lightning flashes to the tower and its vicinity have been observed. This paper presents two examples: the first was an upward negative leader triggered by a close c1oud-to-ground flash and the second was an upward negative flash not associated with previous lightning activity...

  18. Upward nitrate transport by phytoplankton in oceanic waters: balancing nutrient budgets in oligotrophic seas

    Directory of Open Access Journals (Sweden)

    Tracy A. Villareal

    2014-03-01

    Full Text Available In oceanic subtropical gyres, primary producers are numerically dominated by small (1–5 µm diameter pro- and eukaryotic cells that primarily utilize recycled nutrients produced by rapid grazing turnover in a highly efficient microbial loop. Continuous losses of nitrogen (N to depth by sinking, either as single cells, aggregates or fecal pellets, are balanced by both nitrate inputs at the base of the euphotic zone and N2-fixation. This input of new N to balance export losses (the biological pump is a fundamental aspect of N cycling and central to understanding carbon fluxes in the ocean. In the Pacific Ocean, detailed N budgets at the time-series station HOT require upward transport of nitrate from the nutricline (80–100 m into the surface layer (∼0–40 m to balance productivity and export needs. However, concentration gradients are negligible and cannot support the fluxes. Physical processes can inject nitrate into the base of the euphotic zone, but the mechanisms for transporting this nitrate into the surface layer across many 10s of m in highly stratified systems are unknown. In these seas, vertical migration by the very largest (102–103 µm diameter phytoplankton is common as a survival strategy to obtain N from sub-euphotic zone depths. This vertical migration is driven by buoyancy changes rather than by flagellated movement and can provide upward N transport as nitrate (mM concentrations in the cells. However, the contribution of vertical migration to nitrate transport has been difficult to quantify over the required basin scales. In this study, we use towed optical systems and isotopic tracers to show that migrating diatom (Rhizosolenia mats are widespread in the N. Pacific Ocean from 140°W to 175°E and together with other migrating phytoplankton (Ethmodiscus, Halosphaera, Pyrocystis, and solitary Rhizosolenia can mediate time-averaged transport of N (235 µmol N m-2 d-1 equivalent to eddy nitrate injections (242 µmol NO3− m

  19. Traces of pFc' in IVIG interact with human IgG Fc domains and counteract aggregation

    NARCIS (Netherlands)

    Rispens, Theo; Himly, Martin; Ooievaar-de Heer, Pleuni; den Bleker, Tamara H.; Aalberse, Rob C.

    2010-01-01

    To prevent multimer formation, intravenous immunoglobulin (IVIG) is often treated with traces of pepsin. So far, the mechanism behind this treatment has been unclear. Recently, we reported that human IgG4 binds other IgG molecules via Fc-Fc interactions. Here we show that IVIG treated with traces of

  20. The Fc-receptor III of cultured human monocytes. Structural similarity with FcRIII of natural killer cells and role in the extracellular lysis of sensitized erythrocytes

    NARCIS (Netherlands)

    Klaassen, R. J.; Ouwehand, W. H.; Huizinga, T. W.; Engelfriet, C. P.; von dem Borne, A. E.

    1990-01-01

    FcRIII is not present on peripheral blood monocytes, but becomes expressed upon culturing and can be demonstrated on tissue macrophages. We studied the expression of FcRIII of cultured monocytes in detail and compared its structure with FcRIII of neutrophils and NK cells. The cell density of FcRIII

  1. Upward Pricing Pressure in Two-Sided Markets

    NARCIS (Netherlands)

    Affeldt, P.; Filistrucchi, L.; Klein, T.J.

    2012-01-01

    Abstract: Pricing pressure indices have recently been proposed as alternative screening devices for horizontal mergers involving differentiated products. We extend the concept of Upward Pricing Pressure (UPP) proposed by Farrell and Shapiro (2010) to two-sided markets. Examples of such markets are

  2. Upward pricing pressure in two-sided markets

    NARCIS (Netherlands)

    Affeldt, P.; Filistrucchi, L.; Klein, T.J.

    2013-01-01

    Measuring upward pricing pressure (UPP) has recently been proposed by Farrell and Shapiro (2010) as an alternative screening device for horizontal mergers. We extend the concept of UPP to two-sided markets. Examples of such markets are the newspaper market, where the demand for advertising is

  3. Upward Mobility Through Job Restructuring. Personnel Management Series No. 26.

    Science.gov (United States)

    Civil Service Commission, Washington, DC.

    The May, 1974, bulletin issued by the Civil Service Commission deals with job restructuring, the process of realigning job duties to develop technician-type or "bridge" jobs in Federal agencies, as a means to provide upward mobility for employees. Besides being highly beneficial to employees in dead end jobs at low grade levels, job restructuring…

  4. "Fist, Stick, Knife, Gun": Getting Real in Upward Bound.

    Science.gov (United States)

    Pace, Barbara G.; Adkins, Theresa A.

    2002-01-01

    Describes how a teacher found literature for Upward Bound students. Presents Geoffrey Canada's "Fist, Stick, Knife, Gun: A Personal History of Violence in America" as a nonfiction work to provide clarity and connections that might not have been available in a fictional work, yet it had elements of literary fiction that made the text…

  5. Managing upwards: a guide for the foundation year doctor.

    Science.gov (United States)

    Hooke, Rachel

    2009-06-01

    The concept of managing your boss sounds peculiar, as people usually only think of managing staff under them. Nevertheless, adept management 'upwards' can reap dividends. It is not manipulative or sly - it is about good working relations. This article is mainly about dealing with consultants. However, the same principles can apply to other doctors more senior than you in the team.

  6. Leadership Behaviour and Upward Feedback: Findings from a Longitudinal Intervention

    NARCIS (Netherlands)

    D. van Dierendonck (Dirk); C. Haynes (Clare); C. Borrill (Carol); C. Stride (Chris)

    2007-01-01

    textabstractA sample of 48 managers and 308 staff members of a community health care organization took part in a study to investigate the influence of participating in an upward feedback program on leadership behaviour, both as indicated be self-ratings and subordinates’ ratings. The research design

  7. Dynamics of rainwater lenses on upward seeping saline groundwater

    NARCIS (Netherlands)

    Eeman, Sara

    2017-01-01

    Fresh water is generally a limited resource in coastal areas which are often densely populated. In low-lying areas, groundwater is mostly saline and both agriculture and freshwater nature depend on a thin lens of rainwater that is formed by precipitation surplus on top of saline, upward seeping

  8. Upward counterfactual thinking and depression: A meta-analysis.

    Science.gov (United States)

    Broomhall, Anne Gene; Phillips, Wendy J; Hine, Donald W; Loi, Natasha M

    2017-07-01

    This meta-analysis examined the strength of association between upward counterfactual thinking and depressive symptoms. Forty-two effect sizes from a pooled sample of 13,168 respondents produced a weighted average effect size of r=.26, pdesign (cross-sectional versus longitudinal). Significant effect size heterogeneity was observed across sample types, methods of assessing upward counterfactual thinking, and types of depression scale. Significant positive effects were found in studies that employed samples of bereaved individuals, older adults, terminally ill patients, or university students, but not adolescent mothers or mixed samples. Both number-based and Likert-based upward counterfactual thinking assessments produced significant positive effects, with the latter generating a larger effect. All depression scales produced significant positive effects, except for the Psychiatric Epidemiology Research Interview. Research and theoretical implications are discussed in relation to cognitive theories of depression and the functional theory of upward counterfactual thinking, and important gaps in the extant research literature are identified. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. Flux-pinning-induced stresses in a hollow superconducting cylinder with flux creep and viscosity properties

    International Nuclear Information System (INIS)

    Feng, W.J.; Gao, S.W.

    2014-01-01

    Highlights: • Magnetoelastic problem for a superconducting cylinder with a hole is investigated. • The effects of both flux creep and viscous flux flow on stresses are analyzed. • For the FC case, the maximal hoop tensile stress always occurs at hole edge. • For the ZFC case, the maximal hoop stress is not certain to occur at hole edge. - Abstract: The magnetoelastic problem for a superconducting cylinder with a concentric hole placed in a magnetic field is investigated, where the flux creep and viscous flux flow have been considered. The stress distributions are derived and numerical calculated for the descending field in both the zero-field cooling (ZFC) and field cooling (FC) processes. The effects of applied magnetic field, flux creep and viscous flux flow on the maximal radial and hoop stresses are discussed in detail, and some novel phenomena are found. Among others, for the FC case, the maximal hoop tensile stress always occurs at the hole edge, whist for the ZFC case, the maximal stresses including both hoop and radial stresses either occur in the vicinity of the hole or occur at the position of flux frontier in the remagnetization process. For the descending field, in general, both the flux creep and viscosity parameters have important effects on the maximal radial and hoop stresses. All these phenomena are perhaps of vital importance for the application of superconductors

  10. Anisotropic flux pinning in high Tc superconductors

    International Nuclear Information System (INIS)

    Kolesnik, S.; Igalson, J.; Skoskiewicz, T.; Szymczak, R.; Baran, M.; Pytel, K.; Pytel, B.

    1995-01-01

    In this paper we present a comparison of the results of FC magnetization measurements on several Pb-Sr-(Y,Ca)-Cu-O crystals representing various levels of flux pinning. The pinning centers in our crystals have been set up during the crystal growth process or introduced by neutron irradiation. Some possible explanations of the observed effects, including surface barrier, flux-center distribution and sample-shape effects, are discussed. ((orig.))

  11. Fc gamma receptor IIIB (Fc gamma RIIIB) polymorphisms are associated with clinical malaria in Ghanaian children

    DEFF Research Database (Denmark)

    Adu, Bright; Dodoo, Daniel; Adukpo, Selorme

    2012-01-01

    Plasmodium falciparum malaria kills nearly a million people annually. Over 90% of these deaths occur in children under five years of age in sub-Saharan Africa. A neutrophil mediated mechanism, the antibody dependent respiratory burst (ADRB), was recently shown to correlate with protection from...... by allele specific restriction enzyme digestion. FCGR3B-exon 3 was sequenced in 585 children, aged 1 to 12 years living in a malaria endemic region of Ghana. Multivariate logistic regression analysis found no association between Fc¿RIIA-166H/R polymorphism and clinical malaria. The A-allele of FCGR3B-c.233C...... malaria vaccines....

  12. Upward swimming of a sperm cell in shear flow.

    Science.gov (United States)

    Omori, Toshihiro; Ishikawa, Takuji

    2016-03-01

    Mammalian sperm cells are required to swim over long distances, typically around 1000-fold their own length. They must orient themselves and maintain a swimming motion to reach the ovum, or egg cell. Although the mechanism of long-distance navigation is still unclear, one possible mechanism, rheotaxis, was reported recently. This work investigates the mechanism of the rheotaxis in detail by simulating the motions of a sperm cell in shear flow adjacent to a flat surface. A phase diagram was developed to show the sperm's swimming motion under different shear rates, and for varying flagellum waveform conditions. The results showed that, under shear flow, the sperm is able to hydrodynamically change its swimming direction, allowing it to swim upwards against the flow, which suggests that the upward swimming of sperm cells can be explained using fluid mechanics, and this can then be used to further understand physiology of sperm cell navigation.

  13. Construction of a bimolecular fluorescence complementation (BiFC ...

    African Journals Online (AJOL)

    DR. NJ TONUKARI

    2012-08-02

    Aug 2, 2012 ... Accepted 8 June, 2012. Protein–protein interactions are essential for signal transduction in cells. ... BiFC is a novel technology that is used for identifying .... occasional fluorescence was observed, it was very weak ... Light field.

  14. Fc-mediated immune precipitation. III. Visualization by electron microscopy

    DEFF Research Database (Denmark)

    Møller, NPH; Christiansen, Gunna

    1983-01-01

    with either rabbit anti-KLH IgG or anti-KLH F(ab')2 fragments. The Fc-Fc interactions were investigated by reacting these surface-adsorbed antibody-rich KLH immune complexes with soluble, antigen-rich ferritin-anti-ferritin complexes using either rabbit anti-ferritin IgG or the corresponding isomolar F(ab')2...... fragments as antibody. Fc-Fc interactions were indicated by the formation of clusters or ring structures of ferritin molecules, which were only seen when using KLH anti-KLH IgG and ferritin-anti-ferritin IgG complexes. When F(ab')2 fragments were used as antibody, no reaction between KLH anti-KLH complexes...

  15. Liquid velocity in upward and downward air-water flows

    International Nuclear Information System (INIS)

    Sun Xiaodong; Paranjape, Sidharth; Kim, Seungjin; Ozar, Basar; Ishii, Mamoru

    2004-01-01

    Local characteristics of the liquid phase in upward and downward air-water two-phase flows were experimentally investigated in a 50.8-mm inner-diameter round pipe. An integral laser Doppler anemometry (LDA) system was used to measure the axial liquid velocity and its fluctuations. No effect of the flow direction on the liquid velocity radial profile was observed in single-phase liquid benchmark experiments. Local multi-sensor conductivity probes were used to measure the radial profiles of the bubble velocity and the void fraction. The measurement results in the upward and downward two-phase flows are compared and discussed. The results in the downward flow demonstrated that the presence of the bubbles tended to flatten the liquid velocity radial profile, and the maximum liquid velocity could occur off the pipe centerline, in particular at relatively low flow rates. However, the maximum liquid velocity always occurred at the pipe center in the upward flow. Also, noticeable turbulence enhancement due to the bubbles in the two-phase flows was observed in the current experimental flow conditions. Furthermore, the distribution parameter and the void-weighted area-averaged drift velocity were obtained based on the definitions

  16. Cross-Linking GPVI-Fc by Anti-Fc Antibodies Potentiates Its Inhibition of Atherosclerotic Plaque- and Collagen-Induced Platelet Activation

    Directory of Open Access Journals (Sweden)

    Janina Jamasbi, RPh

    2016-04-01

    Full Text Available To enhance the antithrombotic properties of recombinant glycoprotein VI fragment crystallizable (GPVI-Fc, the authors incubated GPVI-Fc with anti-human Fc antibodies to cross-link the Fc tails of GPVI-Fc. Cross-linking potentiated the inhibition of human plaque- and collagen-induced platelet aggregation by GPVI-Fc under static and flow conditions without increasing bleeding time in vitro. Cross-linking with anti-human-Fc Fab2 was even superior to anti-human-Fc immunoglobulin G (IgG. Advanced optical imaging revealed a continuous sheath-like coverage of collagen fibers by cross-linked GPVI-Fc complexes. Cross-linking of GPVI into oligomeric complexes provides a new, highly effective, and probably safe antithrombotic treatment as it suppresses platelet GPVI-plaque interaction selectively at the site of acute atherothrombosis.

  17. Self-assembly and flux closure studies of magnetic nanoparticle rings

    DEFF Research Database (Denmark)

    Wei, Alexander; Kasama, Takeshi; Dunin-Borkowski, Rafal E.

    2011-01-01

    Thermoremanent magnetic nanoparticles (MNPs) can self-assemble into rings through dipolar interactions, when dispersed under appropriate conditions. Analysis of individual MNP rings and clusters by off-axis electron holography reveals bistable flux closure (FC) states at ambient temperatures...

  18. The effect of FcγRIIA and FcγRIIB on coronary artery lesion formation and intravenous immunoglobulin treatment responses in children with Kawasaki disease

    Science.gov (United States)

    Chang, Ling-Sai; Lo, Mao-Hung; Li, Sung-Chou; Yang, Ming-Yu; Hsieh, Kai-Sheng; Kuo, Ho-Chang

    2017-01-01

    Previous research has found patients with the FcγRIIIB NA1 variant having increased risk of intravenous immunoglobulin (IVIG) resistance in Kawasaki disease (KD). Our previous studies revealed that elevated FcγRIIA expression correlated with the susceptibility of KD patients. We conducted this research to determine whether and how Fcγ receptors affect the susceptibility, IVIG treatment response, and coronary artery lesions (CAL) of KD patients. The activating FcγRIIA and inhibitory FcγRIIB methylation levels of seven patients with KD and four control subjects were examined using HumanMethylation27 BeadChip. We enrolled a total of 44 KD patients and 10 control subjects with fevers. We performed real-time RT-PCR to determine the FcγRIIA and FcγRIIB expression levels, as well as a luciferase assay of FcγRIIA. We found a considerable increase in methylation of both FcγRIIA and FcγRIIB in KD patients undergoing IVIG treatment. Promoter methylation of FcγRIIA inhibited reporter activity in K562 cells using luciferase assay. The FcγRIIB mRNA expression levels were not found to increase susceptibility, CAL formation, or IVIG resistance. FcγRIIA mRNA expression levels were significantly higher in IVIG-resistant patients than in those that responded to IVIG during the pre-treatment period. Furthermore, the FcγRIIA/IIB mRNA expression ratio was considerably higher in KD patients with CAL than in those without CAL. FcγRIIA and FcγRIIB both demonstrated increased methylation levels in KD patients that underwent IVIG treatment. FcγRIIA expression influenced the IVIG treatment response of KD patients. The FcγRIIA/IIB mRNA expression ratio was greater in KD patients with CAL formation. PMID:27893416

  19. Dicty_cDB: FC-AC21 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available FC (Link to library) FC-AC21 (Link to dictyBase) - - - Contig-U15104-1 FC-AC21E (Li...nk to Original site) - - - - - - FC-AC21E 527 Show FC-AC21 Library FC (Link to library) Clone ID FC-AC21 (Link to dict...yBase) Atlas ID - NBRP ID - dictyBase ID - Link to Contig Contig-U15104-1 Original site URL http://dict...ce KDSLDVIIFPEMVKLVGLTPNTMEKVLTYFQDNDTIDLSTFPMEIQVEQLSGKYIFICTH KQKDQRCGYCGPILVDQLRDQIKERSLEKEIQVFGTSHVGGHKY... Frames) Frame A: KDSLDVIIFPEMVKLVGLTPNTMEKVLTYFQDNDTIDLSTFPMEIQVEQLSGKYIFICTH KQ

  20. Effects of microparticle size and Fc density on macrophage phagocytosis.

    Directory of Open Access Journals (Sweden)

    Patricia Pacheco

    Full Text Available Controlled induction of phagocytosis in macrophages offers the ability to therapeutically regulate the immune system as well as improve delivery of chemicals or biologicals for immune processing. Maximizing particle uptake by macrophages through Fc receptor-mediated phagocytosis could lead to new delivery mechanisms in drug or vaccine development. Fc ligand density and particle size were examined independently and in combination in order to optimize and tune the phagocytosis of opsonized microparticles. We show the internalization efficiency of small polystyrene particles (0.5 µm to 2 µm is significantly affected by changes in Fc ligand density, while particles greater than 2 µm show little correlation between internalization and Fc density. We found that while macrophages can efficiently phagocytose a large number of smaller particles, the total volume of phagocytosed particles is maximized through the non-specific uptake of larger microparticles. Therefore, larger microparticles may be more efficient at delivering a greater therapeutic payload to macrophages, but smaller opsonized microparticles can deliver bio-active substances to a greater percentage of the macrophage population. This study is the first to treat as independent variables the physical and biological properties of Fc density and microparticle size that initiate macrophage phagocytosis. Defining the physical and biological parameters that affect phagocytosis efficiency will lead to improved methods of microparticle delivery to macrophages.

  1. Utility Assessment of Specificity in Upward Feedback Instruments for Leadership Development

    National Research Council Canada - National Science Library

    Wardak, Theresa

    2003-01-01

    ...) and the other is the recently developed, non-proprietary Upward Feedback Instrument (2002). The Upward Feedback Instrument was designed to measure leadership behaviors at a more specific level...

  2. Mixing of high density solution in vertical upward flow

    International Nuclear Information System (INIS)

    Kumamaru, Hiroshige; Hosogi, Nobuyoshi; Komada, Toshiaki; Fujiwara, Yoshiki

    1999-01-01

    Experimental and analytical studies have been performed in order to provide fundamental data and a numerical calculation model on the mixing of boric acid solution, injected from the standby liquid control system (SLCS), under a low natural circulation flow during an ATWS in a BWR. First, fundamental experiments on the mixing of high-density solution in vertically-upward water flow have been performed by using a small apparatus. Mixing patterns observed in the experiments have been classified to two groups, i.e. complete mixing (entrainment) and incomplete mixing (entrainment). In the complete mixing, the injected high-density solution is mixed (entrained) completely into the vertically-upward water flow. From the experiments, the minimum water flow rates in which the complete mixing (entrainment) is achieved have been obtained for various solution densities and solution injection rates. Secondly, two-dimensional numerical calculations have been performed. A continuity equation for total fluid, momentum equations in two directions and a continuity equation for solute are solved by using the finite difference method for discretization method and by following the MAC method for solution procedure. The calculations have predicted nearly the minimum water flow rate in which the complete mixing is achieved, while the calculations have been performed only for one combination of the solution density and solution injection rate until now. (author)

  3. Analysis of the atmospheric upward radiation in low latitude area

    Science.gov (United States)

    Li, Haiying; Wu, Zhensen; Lin, Leke; Lu, Changsheng

    2016-10-01

    Remote sensing using THz wave has irreplaceable advantage comparing to the microwave and the infrared waves, and study on the THz remote sensing become more and more popular in recent years. The major applications of the remote sensing in THz wavelengths are the retrieval of the atmospheric parameters and the microphysical information of the ice cloud. The remote sensing of the atmosphere is based on the radiation of THz wave along the earth-space path of which the most significant part is the upward radiation of the atmosphere. The upward radiation of the atmosphere in sunny day in the low latitude area is computed and analyzed in this paper. The absorption of THz wave by the atmosphere is calculated using the formulations illustrated in the Recommendation ITU-R P.676 to save machine hour, the frequency range is then restricted below 1THz. The frequencies used for the retrieval of atmospheric parameters such as temperature and water content are usually a few hundred GHz, at the lower end of THz wavelengths, so this frequency range is sufficient. The radiation contribution of every atmospheric layer for typical frequencies such as absorption window frequencies and peak frequencies are analyzed. Results show that at frequencies which absorption is severe, information about lower atmosphere cannot reach the receiver onboard a satellite or other high platforms due to the strong absorption along the path.

  4. Live visualization of genomic loci with BiFC-TALE.

    Science.gov (United States)

    Hu, Huan; Zhang, Hongmin; Wang, Sheng; Ding, Miao; An, Hui; Hou, Yingping; Yang, Xiaojing; Wei, Wensheng; Sun, Yujie; Tang, Chao

    2017-01-11

    Tracking the dynamics of genomic loci is important for understanding the mechanisms of fundamental intracellular processes. However, fluorescent labeling and imaging of such loci in live cells have been challenging. One of the major reasons is the low signal-to-background ratio (SBR) of images mainly caused by the background fluorescence from diffuse full-length fluorescent proteins (FPs) in the living nucleus, hampering the application of live cell genomic labeling methods. Here, combining bimolecular fluorescence complementation (BiFC) and transcription activator-like effector (TALE) technologies, we developed a novel method for labeling genomic loci (BiFC-TALE), which largely reduces the background fluorescence level. Using BiFC-TALE, we demonstrated a significantly improved SBR by imaging telomeres and centromeres in living cells in comparison with the methods using full-length FP.

  5. Rapid desensitization of mice with anti-FcγRIIb/FcγRIII mAb safely prevents IgG-mediated anaphylaxis.

    Science.gov (United States)

    Khodoun, Marat V; Kucuk, Zeynep Yesim; Strait, Richard T; Krishnamurthy, Durga; Janek, Kevin; Clay, Corey D; Morris, Suzanne C; Finkelman, Fred D

    2013-12-01

    Stimulatory IgG receptors (FcγRs) on bone marrow-derived cells contribute to the pathogenesis of several autoimmune and inflammatory disorders. Monoclonal antibodies that block FcγRs might suppress these diseases, but they can induce anaphylaxis. We wanted to determine whether a rapid desensitization approach can safely suppress IgG/FcγR-mediated anaphylaxis. Mice were injected with serially increasing doses of 2.4G2, a rat mAb that blocks the inhibitory FcγR, FcγRIIb, and the stimulatory receptor, FcγRIII. Rectal temperature was used to detect the development of anaphylaxis. Passive and active IgG-mediated anaphylaxis were evaluated in mice that had been rapidly desensitized with 2.4G2 or mock-desensitized in mice in which monocyte/macrophages, basophils, or neutrophils had been depleted or desensitized and in mice in which FcγRI, FcγRIII, and/or FcγRIV had been deleted or blocked. Rapid desensitization with 2.4G2 prevented 2.4G2-induced shock and completely suppressed IgG-mediated anaphylaxis. Rapid desensitization of ovalbumin-sensitized mice with 2.4G2 was safer and more effective than rapid desensitization with ovalbumin. 2.4G2 treatment completely blocked FcγRIII and removed most FcγRI and FcγRIV from nucleated peripheral blood cells. Because IgG(2a)-mediated anaphylaxis was partially FcγRI and FcγRIV dependent, the effects of 2.4G2 on FcγRI and FcγRIV were probably crucial for its complete inhibition of IgG(2a)-mediated anaphylaxis. IgG(2a)-mediated anaphylaxis was partially inhibited by depletion or desensitization of monocyte/macrophages, basophils, or neutrophils. IgG-mediated anaphylaxis can be induced by ligation of FcγRI, FcγRIII, or FcγRIV on monocycte/macrophages, basophils, or neutrophils and can be safely suppressed by rapid desensitization with anti-FcγRII/RIII mAb. A similar approach may safely suppress other FcγR-dependent immunopathology. Published by Mosby, Inc.

  6. Importance of neonatal FcR in regulating the serum half-life of therapeutic proteins containing the Fc domain of human IgG1: a comparative study of the affinity of monoclonal antibodies and Fc-fusion proteins to human neonatal FcR.

    Science.gov (United States)

    Suzuki, Takuo; Ishii-Watabe, Akiko; Tada, Minoru; Kobayashi, Tetsu; Kanayasu-Toyoda, Toshie; Kawanishi, Toru; Yamaguchi, Teruhide

    2010-02-15

    The neonatal FcR (FcRn) binds to the Fc domain of IgG at acidic pH in the endosome and protects IgG from degradation, thereby contributing to the long serum half-life of IgG. To date, more than 20 mAb products and 5 Fc-fusion protein products have received marketing authorization approval in the United States, the European Union, or Japan. Many of these therapeutic proteins have the Fc domain of human IgG1; however, the serum half-lives differ in each protein. To elucidate the role of FcRn in the pharmacokinetics of Fc domain-containing therapeutic proteins, we evaluated the affinity of the clinically used human, humanized, chimeric, or mouse mAbs and Fc-fusion proteins to recombinant human FcRn by surface plasmon resonance analysis. The affinities of these therapeutic proteins to FcRn were found to be closely correlated with the serum half-lives reported from clinical studies, suggesting the important role of FcRn in regulating their serum half-lives. The relatively short serum half-life of Fc-fusion proteins was thought to arise from the low affinity to FcRn. The existence of some mAbs having high affinity to FcRn and a short serum half-life, however, suggested the involvement of other critical factor(s) in determining the serum half-life of such Abs. We further investigated the reason for the relatively low affinity of Fc-fusion proteins to FcRn and suggested the possibility that the receptor domain of Fc-fusion protein influences the structural environment of the FcRn binding region but not of the FcgammaRI binding region of the Fc domain.

  7. Experimental heat transfer to supercritical carbon dioxide flowing upward vertical tube with highly conducting surroundings

    International Nuclear Information System (INIS)

    Son, Hyung M.; Suh, Kune Y.

    2012-01-01

    Highlights: ► Performed experiment for the upward SCO 2 flow surrounded by highly conducting metal. ► Selected dimensionless groups representing the property variations and buoyancy. ► Developed the heat transfer correlation for the mixed thermal boundary condition. ► Wrote a finite element heat transfer code to find the appropriate correlation. ► Coupled the 1D convection and 2D heat conduction via heat transfer coefficient. - Abstract: This paper presents heat transfer characteristics of supercritical carbon dioxide flow inside vertical circular pipe surrounded by highly conducting material, and develops an adequate tool to test the performance of available heat transfer correlations with. The possible situations are illustrated for the nuclear power plant to which the above-mentioned geometric configuration might be applicable. An experimental loop with vertical circular geometry is designed and constructed to test the upward flow in supercritical state when the axial heat transfer is enhanced by the surrounding metals, resulting in a wall boundary condition between the constant heat flux and temperature. The set of correlations and important findings are critically reviewed from extensive literature survey. Incorporating nondimensional groups resorting to past insights from the available literature, a convective heat transfer correlation is proposed. The optimization procedure is described which utilizes a random walk method along with the in-house finite element heat transfer code to determine the coefficients of the proposed heat transfer correlation. The proposed methodology can be applied to evaluation of heat transfer when the heat transfer coefficient data cannot directly be determined from the experiment.

  8. Single chain Fc-dimer-human growth hormone fusion protein for improved drug delivery.

    Science.gov (United States)

    Zhou, Li; Wang, Hsuan-Yao; Tong, Shanshan; Okamoto, Curtis T; Shen, Wei-Chiang; Zaro, Jennica L

    2017-02-01

    Fc fusion protein technology has been successfully used to generate long-acting forms of several protein therapeutics. In this study, a novel Fc-based drug carrier, single chain Fc-dimer (sc(Fc) 2 ), was designed to contain two Fc domains recombinantly linked via a flexible linker. Since the Fc dimeric structure is maintained through the flexible linker, the hinge region was omitted to further stabilize it against proteolysis and reduce FcγR-related effector functions. The resultant sc(Fc) 2 candidate preserved the neonatal Fc receptor (FcRn) binding. sc(Fc) 2 -mediated delivery was then evaluated using a therapeutic protein with a short plasma half-life, human growth hormone (hGH), as the protein drug cargo. This novel carrier protein showed a prolonged in vivo half-life and increased hGH-mediated bioactivity compared to the traditional Fc-based drug carrier. sc(Fc) 2 technology has the potential to greatly advance and expand the use of Fc-technology for improving the pharmacokinetics and bioactivity of protein therapeutics. Copyright © 2016 Elsevier Ltd. All rights reserved.

  9. A Heat Transfer Correlation in a Vertical Upward Flow of CO{sub 2} at Supercritical Pressures

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Hyung Rae; Bae, Yoon Yeong; Song, Jin Ho; Kim, Hwan Yeol [Korea Atomic Energy Research Institute, Taejon (Korea, Republic of)

    2006-07-01

    Heat transfer data has been collected in the heat transfer test loop, named SPHINX (Supercritical Pressure Heat Transfer Investigation for NeXt generation), in KAERI. The facility primarily aims at the generation of heat transfer data in the flow conditions and geometries relevant to SCWR (SuperCritical Water-cooled Reactor). The produced data will aid the thermohydraulic design of a reactor core. The loop uses carbon dioxide, and later the results will be scaled to the water flows. The heat transfer data has been collected for a vertical upward flow in a circular tube with varying mass fluxes, heat fluxes, and operating pressures. The results are compared with the existing correlations and a new correlation is proposed by fine-tuning the one of the existing correlations.

  10. HAL/S-FC compiler system functional specification

    Science.gov (United States)

    1974-01-01

    Compiler organization is discussed, including overall compiler structure, internal data transfer, compiler development, and code optimization. The user, system, and SDL interfaces are described, along with compiler system requirements. Run-time software support package and restrictions and dependencies are also considered of the HAL/S-FC system.

  11. Fc receptor gamma subunit polymorphisms and systemic lupus erythematosus

    International Nuclear Information System (INIS)

    Al-Ansari, Aliya; Ollier, W.E.; Gonzalez-Gay, Miguel A.; Gul, Ahmet; Inanac, Murat; Ordi, Jose; Teh, Lee-Suan; Hajeer, Ali H.

    2004-01-01

    To investigate the possible association between Fc receptor gamma polymorphisms and systemic lupus erythematosus (SLE). We have investigated the full FcR gamma gene for polymorphisms using polymerase chain reaction (PCR)-single strand confirmational polymorphisms and DNA sequencing .The polymorphisms identified were genotype using PCR-restriction fragment length polymorphism. Systemic lupus erythematosus cases and controls were available from 3 ethnic groups: Turkish, Spanish and Caucasian. The study was conducted in the year 2001 at the Arthritis Research Campaign, Epidemiology Unit, Manchester University Medical School, Manchester, United Kingdom. Five single nucleotide polymorphisms were identified, 2 in the promoter, one in intron 4 and, 2 in the 3'UTR. Four of the 5 single nucleotide polymorphisms (SNPs) were relatively common and investigated in the 3 populations. Allele and genotype frequencies of all 4 investigated SNPs were not statistically different cases and controls. fc receptor gamma gene does not appear to contribute to SLE susceptibility. The identified polymorphisms may be useful in investigating other diseases where receptors containing the FcR gamma subunit contribute to the pathology. (author)

  12. The neonatal Fc receptor (FcRn) binds independently to both sites of the IgG homodimer with identical affinity.

    Science.gov (United States)

    Abdiche, Yasmina Noubia; Yeung, Yik Andy; Chaparro-Riggers, Javier; Barman, Ishita; Strop, Pavel; Chin, Sherman Michael; Pham, Amber; Bolton, Gary; McDonough, Dan; Lindquist, Kevin; Pons, Jaume; Rajpal, Arvind

    2015-01-01

    The neonatal Fc receptor (FcRn) is expressed by cells of epithelial, endothelial and myeloid lineages and performs multiple roles in adaptive immunity. Characterizing the FcRn/IgG interaction is fundamental to designing therapeutic antibodies because IgGs with moderately increased binding affinities for FcRn exhibit superior serum half-lives and efficacy. It has been hypothesized that 2 FcRn molecules bind an IgG homodimer with disparate affinities, yet their affinity constants are inconsistent across the literature. Using surface plasmon resonance biosensor assays that eliminated confounding experimental artifacts, we present data supporting an alternate hypothesis: 2 FcRn molecules saturate an IgG homodimer with identical affinities at independent sites, consistent with the symmetrical arrangement of the FcRn/Fc complex observed in the crystal structure published by Burmeister et al. in 1994. We find that human FcRn binds human IgG1 with an equilibrium dissociation constant (KD) of 760 ± 60 nM (N = 14) at 25°C and pH 5.8, and shows less than 25% variation across the other human subtypes. Human IgG1 binds cynomolgus monkey FcRn with a 2-fold higher affinity than human FcRn, and binds both mouse and rat FcRn with a 10-fold higher affinity than human FcRn. FcRn/IgG interactions from multiple species show less than a 2-fold weaker affinity at 37°C than at 25°C and appear independent of an IgG's variable region. Our in vivo data in mouse and rat models demonstrate that both affinity and avidity influence an IgG's serum half-life, which should be considered when choosing animals, especially transgenic systems, as surrogates.

  13. Coordinate expression of activating Fc gamma receptors I and III and inhibiting Fc gamma receptor type II in the determination of joint inflammation and cartilage destruction during immune complex-mediated arthritis.

    NARCIS (Netherlands)

    Nabbe, K.C.A.M.; Blom, A.B.; Holthuysen, A.E.M.; Boross, P.; Roth, J.; Verbeek, S.; Lent, P.L.E.M. van; Berg, W.B. van den

    2003-01-01

    OBJECTIVE: To study the role of the activating Fc gamma receptor types I and III (Fc gamma RI and Fc gamma RIII, respectively) and the inhibiting Fc gamma receptor II (Fc gamma RII) in inflammation and in various aspects of cartilage destruction during arthritis that is solely induced by immune

  14. Dicty_cDB: FC-AY04 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available FC (Link to library) FC-AY04 (Link to dictyBase) - - - Contig-U16521-1 FC-AY04Z (Li...nk to Original site) - - FC-AY04Z 583 - - - - Show FC-AY04 Library FC (Link to library) Clone ID FC-AY04 (Link to dict...yBase) Atlas ID - NBRP ID - dictyBase ID - Link to Contig Contig-U16521-1 Original site URL http://dict...10 4 CA753827 |AF402814_1 ( AF402814 ) 40S ribosomal protein S6 [Ictalurus puncta...0.00 m_ : 1.00 92.0 %: cytoplasmic 4.0 %: mitochondrial 4.0 %: nuclear >> prediction for FC-AY04 is cyt 5' e

  15. Dicty_cDB: FC-BF01 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available FC (Link to library) FC-BF01 (Link to dictyBase) - - - Contig-U15105-1 FC-BF01Z (Li...nk to Original site) - - FC-BF01Z 674 - - - - Show FC-BF01 Library FC (Link to library) Clone ID FC-BF01 (Link to dict...yBase) Atlas ID - NBRP ID - dictyBase ID - Link to Contig Contig-U15105-1 Original site URL http://dict...402813_1( AF402813 |pid:none) Ictalurus punctatus 40S ribosomal ... 260 3e-68 AJ783868_1( AJ783868 |pid:none...lasmic 8.0 %: mitochondrial 4.0 %: nuclear >> prediction for FC-BF01 is cyt 5' end seq. ID - 5' end seq. - L

  16. Dicty_cDB: FC-AK01 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available FC (Link to library) FC-AK01 (Link to dictyBase) - - - Contig-U15038-1 FC-AK01E (Li...nk to Original site) - - - - - - FC-AK01E 996 Show FC-AK01 Library FC (Link to library) Clone ID FC-AK01 (Link to dict...yBase) Atlas ID - NBRP ID - dictyBase ID - Link to Contig Contig-U15038-1 Original site URL http://dict...s clone omyk-evn... 172 6e-79 AF401557_1( AF401557 |pid:none) Ictalurus punctatus...reticulum 4.0 %: vacuolar >> prediction for FC-AK01 is mit 5' end seq. ID - 5' end seq. - Length of 5' end s

  17. Dicty_cDB: FC-BC16 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available FC (Link to library) FC-BC16 (Link to dictyBase) - - - Contig-U15105-1 FC-BC16Z (Li...nk to Original site) - - FC-BC16Z 620 - - - - Show FC-BC16 Library FC (Link to library) Clone ID FC-BC16 (Link to dict...yBase) Atlas ID - NBRP ID - dictyBase ID - Link to Contig Contig-U15105-1 Original site URL http://dict...4 2e-66 AY961522_1( AY961522 |pid:none) Lysiphlebus testaceipes ribosomal ... 254 2e-66 AF402813_1( AF402813 |pid:none) Ict...hondrial 4.0 %: nuclear >> prediction for FC-BC16 is cyt 5' end seq. ID - 5' end seq. - Length of 5' end seq

  18. The collective roots and rewards of upward educational mobility.

    Science.gov (United States)

    Shahrokni, Shirin

    2018-02-02

    Drawing on in-depth interviews with descendants of North African working-class immigrants admitted to elite higher institutions in France, this paper investigates the under-researched role of family dynamics in facilitating upward educational mobility and informing the experience of social ascension. It shows that concrete mobility strategies, such as authoritative parenting and close mentorship from older siblings have been deployed to enable the respondents' educational attainment. Moreover, a set of moral resources transmitted through stories about family-rooted aspirations and stories about post-migration hardships and sacrifices have contributed to forging strong motivational dispositions that have facilitated school success among the respondents. These resources have further shaped the symbolic significance the interviewees associate with mobility. In contrast with the dominant individual-centred narrative of success, for second-generation North African immigrants, mobility represents a powerful way of 'giving back' to former-generation migrants whose mobility dreams often had to be relinquished. The respondents also position themselves as role-models for other youths of racially and socially disadvantaged backgrounds: their mobility pathways are described as vital for collective advancements particularly through the sense of minority empowerment these generate. © London School of Economics and Political Science 2018.

  19. Numerical Simulation on Forced Convective Condensation of Steam Upward Flow in a Vertical Pipe

    Directory of Open Access Journals (Sweden)

    Guo-Dong Qiu

    2014-05-01

    Full Text Available A transient three-dimensional volume of fluid (VOF simulation on condensation of upward flow of wet steam inside a 12 mm i.d. vertical pipe is presented. The effect of gravity and surface tension are taken into account. A uniform wall temperature has been fixed as boundary conditions. The mass flux is 130~6400 kg m−2's−1 and the turbulence inside the vapor phase and liquid phase have been handled by Reynolds stress model (RSM. The vapor quality of fluid is 0~0.4. The numerical simulation results show that, in all the simulation conditions, the bubbly flow, slug flow, churn flow, wispy annular flow, and annular flow are observed; in addition, the results of flow pattern are in good agreement with the regime map from Hewitt and Roberts. The typical velocity field characteristic of each flow pattern and the effect of velocity field on heat transfer of condensation are analyzed, indicating that the slug flow and churn flow have obvious local eddy. However, no obvious eddy is observed in other flow patterns and the streamlines are almost parallel to the flow direction. The simulation results of heat transfer coefficients and frictional pressure drop show good agreement with the correlations from existing literatures.

  20. An assessment of void fraction correlations for vertical upward steam-water flow

    International Nuclear Information System (INIS)

    Vijayan, P.K.; Maruthi Ramesh, N.; Pilkhwal, D.S.; Saha, D.

    1997-01-01

    An assessment of sixteen void fraction correlations have been carried out using experimental void fraction data compiled from open literature for vertical upward steam-water flow. Nearly 80% of all the data pertained to natural circulation flow. This assessment showed that best prediction is obtained by Chexal et al. (1996) correlation followed by Hughmark (1965) and the Mochizuki and Ishii (1992) correlations. The Mochizuki-Ishii correlation is found to satisfy all the three limiting conditions whereas Chexal et al. (1996) correlation satisfies all the limiting conditions at moderately high mass fluxes (greater than 140 kg/m 2 s) while Hughmark correlation satisfies only one of the three limiting conditions. The available void fraction data in the open literature for steam-water two-phase flow lies predominantly in the low quality region. This is the reason why correlations like Hughmark which do not satisfy the upper limiting condition (i.e. at x=1, α=1) perform rather well in assessments. Additional work is required for the generation of high quality (greater than 40%) void fraction data. (author)

  1. 21 CFR 866.5530 - Immunoglobulin G (Fc fragment specific) immunological test system.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Immunoglobulin G (Fc fragment specific... Test Systems § 866.5530 Immunoglobulin G (Fc fragment specific) immunological test system. (a) Identification. An immunoglobulin G (Fc fragment specific) immunological test system is a device that consists of...

  2. A strategy for bacterial production of a soluble functional human neonatal Fc receptor

    DEFF Research Database (Denmark)

    Andersen, Jan Terje; Justesen, Sune; Berntzen, Gøril

    2008-01-01

    The major histocompatibility complex (MHC) class I related receptor, the neonatal Fc receptor (FcRn), rescues immunoglobulin G (IgG) and albumin from lysosomal degradation by recycling in endothelial cells. FcRn also contributes to passive immunity by mediating transport of IgG from mother to fetus...

  3. Prophylactic anti-D preparations display variable decreases in Fc-fucosylation of anti-D.

    NARCIS (Netherlands)

    Kapur, R.; Della Valle, L.; Verhagen, O.J.; Hipgrave Ederveen, A.; Ligthart, P.; de Haas, M.; Kumpel, B.; Wuhrer, M.; van der Schoot, C.E.; Vidarsson, G.

    2015-01-01

    Background RhIG is obtained from hyperimmunized healthy anti-D donors (HIDs) boosted with D+ red blood cells (RBCs). One hypothesis for its mechanism of action is fast clearance of opsonized D+ RBCs through Fcγ receptor (FcγR)III. Levels of immunoglobulin (Ig)G Fc-fucosylation influence interactions

  4. Prophylactic anti-D preparations display variable decreases in Fc-fucosylation of anti-D

    NARCIS (Netherlands)

    Kapur, Rick; Della Valle, Luciana; Verhagen, Onno J. H. M.; Hipgrave Ederveen, Agnes; Ligthart, Peter; de Haas, Masja; Kumpel, Belinda; Wuhrer, Manfred; van der Schoot, C. Ellen; Vidarsson, Gestur

    2015-01-01

    RhIG is obtained from hyperimmunized healthy anti-D donors (HIDs) boosted with D+ red blood cells (RBCs). One hypothesis for its mechanism of action is fast clearance of opsonized D+ RBCs through Fcγ receptor (FcγR)III. Levels of immunoglobulin (Ig)G Fc-fucosylation influence interactions with

  5. Regulation of Monoclonal Antibody Immunotherapy by FcγRIIB.

    Science.gov (United States)

    Stopforth, Richard J; Cleary, Kirstie L S; Cragg, Mark S

    2016-05-01

    Monoclonal antibodies (mAb) are revolutionising the treatment of many different diseases. Given their differing mode of action compared to most conventional chemotherapeutics and small molecule inhibitors, they possess the potential to be independent of common modes of treatment resistance and can typically be combined readily with existing treatments without dose-limiting toxicity. However, treatments with mAb rarely result in cure and so a full understanding of how these reagents work and can be optimised is key for their subsequent improvement. Here we review how an understanding of the biology of the inhibitory Fc receptor, FcγRIIB (CD32B), is leading to the development of improved mAb treatments.

  6. Fcγ receptor-mediated inflammation inhibits axon regeneration.

    Directory of Open Access Journals (Sweden)

    Gang Zhang

    Full Text Available Anti-glycan/ganglioside antibodies are the most common immune effectors found in patients with Guillain-Barré Syndrome, which is a peripheral autoimmune neuropathy. We previously reported that disease-relevant anti-glycan autoantibodies inhibited axon regeneration, which echo the clinical association of these antibodies and poor recovery in Guillain-Barré Syndrome. However, the specific molecular and cellular elements involved in this antibody-mediated inhibition of axon regeneration are not previously defined. This study examined the role of Fcγ receptors and macrophages in the antibody-mediated inhibition of axon regeneration. A well characterized antibody passive transfer sciatic nerve crush and transplant models were used to study the anti-ganglioside antibody-mediated inhibition of axon regeneration in wild type and various mutant and transgenic mice with altered expression of specific Fcγ receptors and macrophage/microglia populations. Outcome measures included behavior, electrophysiology, morphometry, immunocytochemistry, quantitative real-time PCR, and western blotting. We demonstrate that the presence of autoantibodies, directed against neuronal/axonal cell surface gangliosides, in the injured mammalian peripheral nerves switch the proregenerative inflammatory environment to growth inhibitory milieu by engaging specific activating Fcγ receptors on recruited monocyte-derived macrophages to cause severe inhibition of axon regeneration. Our data demonstrate that the antibody orchestrated Fcγ receptor-mediated switch in inflammation is one mechanism underlying inhibition of axon regeneration. These findings have clinical implications for nerve repair and recovery in antibody-mediated immune neuropathies. Our results add to the complexity of axon regeneration in injured peripheral and central nervous systems as adverse effects of B cells and autoantibodies on neural injury and repair are increasingly recognized.

  7. Surveillance for Intracellular Antibody by Cytosolic Fc Receptor TRIM21

    Directory of Open Access Journals (Sweden)

    William A. McEwan

    2016-11-01

    Full Text Available TRIM21 has emerged as an atypical Fc receptor that is broadly conserved and widely expressed in the cytoplasm of mammalian cells. Viruses that traffic surface-bound antibodies into the cell during infection recruit TRIM21 via a high affinity interaction between Fc and TRIM21 PRYSPRY domain. Following binding of intracellular antibody, TRIM21 acts as both antiviral effector and sensor for innate immune signalling. These activities serve to reduce viral replication by orders of magnitude in vitro and contribute to host survival during in vivo infection. Neutralization occurs rapidly after detection and requires the activity of the ubiquitin-proteasome system. The microbial targets of this arm of intracellular immunity are still being identified: TRIM21 activity has been reported following infection by several non-enveloped viruses and intracellular bacteria. These findings extend the sphere of influence of antibodies to the intracellular domain and have broad implications for immunity. TRIM21 has been implicated in the chronic auto-immune condition systemic lupus erythematosus and is itself an auto-antigen in Sjögren’s syndrome. This review summarises our current understanding of TRIM21’s role as a cytosolic Fc receptor and briefly discusses pathological circumstances where intracellular antibodies have been described, or are hypothesized to occur, and may benefit from further investigations of the role of TRIM21.

  8. Reproduction of the FC/DFC units in nucleoli.

    Science.gov (United States)

    Smirnov, Evgeny; Hornáček, Matúš; Kováčik, Lubomír; Mazel, Tomáš; Schröfel, Adam; Svidenská, Silvie; Skalníková, Magdalena; Bartová, Eva; Cmarko, Dušan; Raška, Ivan

    2016-04-25

    The essential structural components of the nucleoli, Fibrillar Centers (FC) and Dense Fibrillar Components (DFC), together compose FC/DFC units, loci of rDNA transcription and early RNA processing. In the present study we followed cell cycle related changes of these units in 2 human sarcoma derived cell lines with stable expression of RFP-PCNA (the sliding clamp protein) and GFP-RPA43 (a subunit of RNA polymerase I, pol I) or GFP-fibrillarin. Correlative light and electron microscopy analysis showed that the pol I and fibrillarin positive nucleolar beads correspond to individual FC/DFC units. In vivo observations showed that at early S phase, when transcriptionally active ribosomal genes were replicated, the number of the units in each cell increased by 60-80%. During that period the units transiently lost pol I, but not fibrillarin. Then, until the end of interphase, number of the units did not change, and their duplication was completed only after the cell division, by mid G1 phase. This peculiar mode of reproduction suggests that a considerable subset of ribosomal genes remain transcriptionally silent from mid S phase to mitosis, but become again active in the postmitotic daughter cells.

  9. Effects of intergroup upward comparison, trait self-esteem, and identity shift on state self-esteem and affect in upward comparison with in-group members

    OpenAIRE

    Isobe, Chikae; Ura, Mitsuhiro

    2006-01-01

    The present study investigated factors that protect people low in trait self-esteem (Low-SEs), who may be less skilled at constructing information in self-enhancing manners, from threats after interpersonal upward comparison with in-group members. We hypothesized that even Low-SEs can maintain their state self-esteem under intergroup upward comparison. Furthermore, this study explored the possibility that individuals used identity-shift, a strategy to maintain their personal identity, even in...

  10. Analytical FcRn affinity chromatography for functional characterization of monoclonal antibodies

    Science.gov (United States)

    Schlothauer, Tilman; Rueger, Petra; Stracke, Jan Olaf; Hertenberger, Hubert; Fingas, Felix; Kling, Lothar; Emrich, Thomas; Drabner, Georg; Seeber, Stefan; Auer, Johannes; Koch, Stefan; Papadimitriou, Apollon

    2013-01-01

    The neonatal Fc receptor (FcRn) is important for the metabolic fate of IgG antibodies in vivo. Analysis of the interaction between FcRn and IgG in vitro might provide insight into the structural and functional integrity of therapeutic IgG that may affect pharmacokinetics (PK) in vivo. We developed a standardized pH gradient FcRn affinity liquid chromatography method with conditions closely resembling the physiological mechanism of interaction between IgG and FcRn. This method allows the separation of molecular IgG isoforms, degradation products and engineered molecules based on their affinity to FcRn. Human FcRn was immobilized on the column and a linear pH gradient from pH 5.5 to 8.8 was applied. FcRn chromatography was used in comparison to surface plasmon resonance to characterize different monoclonal IgG preparations, e.g., oxidized or aggregated species. Wild-type and engineered IgGs were compared in vitro by FcRn chromatography and in vivo by PK studies in huFcRn transgenic mice. Analytical FcRn chromatography allows differentiation of IgG samples and variants by peak pattern and retention time profile. The method can distinguish: 1) IgGs with different Fabs, 2) oxidized from native IgG, 3) aggregates from monomer and 4) antibodies with mutations in the Fc part from wild-type IgGs. Changes in the FcRn chromatographic behavior of mutant IgGs relative to the wild-type IgG correlate to changes in the PK profile in the FcRn transgenic mice. These results demonstrate that FcRn affinity chromatography is a useful new method for the assessment of IgG integrity. PMID:23765230

  11. Comparison of the Fc fragment from a human IgG1 and its CH2, pFc', and tFc' subfragments. A study using reductive methylation and 13C NMR

    International Nuclear Information System (INIS)

    Jentoft, J.E.; Rayford, R.

    1989-01-01

    The Fc fragment of a human monoclonal IgG1 was compared with subfragments containing (a) the intact CH2 domain (CH2 fragment) or (b) the intact CH3 domain (pFc' and tFc' fragments). All fragments were reductively 13 C-methylated and their resulting dimethyllysyl resonances characterized in 0.1 M KCl as a function of pH by 13 C NMR spectroscopy. Seven resonances were characterized for the 18 lysine residues of the Fc fragment, eight for the 12 lysines of the CH2 fragment, and five each for the 9 lysines of the pFc' and the 6 lysines of the tFc' fragments, respectively. The multiplicity of resonances indicates that the lysine residues in each fragment exist in a variety of microenvironments and that the fragments are all highly structured. The correspondence between 6 of the 12 or 13 perturbed lysine residues in the Fc fragment and the smaller subfragments indicates that the conformation of the CH2 and CH3 domains is largely unchanged in the smaller fragments. However, in addition to three lysines at the CH2-CH3 domain interface, whose environments were known to be disrupted in the smaller fragments, three or four lysine residues have somewhat different properties in the Fc fragment and in the subfragments, indicating that some local perturbations are included in the domain structure in the subfragments

  12. Passive Superconducting Flux Conservers for Rotating-Magnetic-Field-Driven Field-Reversed Configurations

    International Nuclear Information System (INIS)

    EOz, E.; Myers, C.E.; Edwards, M.R.; Berlinger, B.; Brooks, A.; Cohen, S.A.

    2011-01-01

    The Princeton Field-Reversed Configuration (PFRC) experiment employs an odd-parity rotating magnetic field (RMFo) current drive and plasma heating system to form and sustain high-β plasmas. For radial confinement, an array of coaxial, internal, passive, flux-conserving (FC) rings applies magnetic pressure to the plasma while still allowing radio-frequency RMF o from external coils to reach the plasma. The 3 ms pulse duration of the present experiment is limited by the skin time (τ fc ) of its room-temperature copper FC rings. To explore plasma phenomena with longer characteristic times, the pulse duration of the next-generation PFRC-2 device will exceed 100 ms, necessitating FC rings with τ fc > 300 ms. In this paper we review the physics of internal, discrete, passive FCs and describe the evolution of the PFRC's FC array. We then detail new experiments that have produced higher performance FC rings that contain embedded high-temperature superconducting (HTS) tapes. Several HTS tape winding configurations have been studied and a wide range of extended skin times, from 0.4 s to over 10 3 s, has been achieved. The new FC rings must carry up to 3 kA of current to balance the expected PFRC-2 plasma pressure, so the dependence of the HTS-FC critical current on the winding configuration and temperature was also studied. From these experiments, the key HTS-FC design considerations have been identified and HTS-FC rings with the desired performance characteristics have been produced.

  13. Mixed convection heat transfer to carbon dioxide flowing upward and downward in a vertical tube and an annular channel

    International Nuclear Information System (INIS)

    Bae, Yoon Y.

    2011-01-01

    Highlights: → Experimental results of heat transfer at a supercritical pressure for a tube with an inner diameter of 4.57 mm and a corresponding annular channel (8 mm x 10 mm, 1 mm gap) were compared each other. → Effect of various parameters such as pressure, flow direction, diameter, channel shape, was investigated. → Existing correlation for supercritical heat transfer were evaluated against the experimental data. → Some unusual characteristics of supercritical heat transfer, such as overshoot and non-monotonic behavior against buoyancy parameter, were discussed. → New correlations were proposed based on the experimental data. - Abstract: This paper addresses three main subjects in supercritical heat transfer: (1) difference in thermal characteristics between upward and downward flows; (2) effect of simulating flow channel shape; (3) evaluation of the existing supercritical heat transfer correlations. To achieve the objectives, a series of experiments was carried out with CO 2 flowing upward and downward in a circular tube with an inner diameter of 4.57 mm and an annular channel created between a tube with an inner diameter of 10 mm and a heater rod with an outer diameter of 8 mm. The working fluid, CO 2 , has been regarded as an appropriate modeling fluid for water, primarily because of their similarity in property variations against reduced temperatures. The mass flux ranged from 400 to 1200 kg/m 2 s. The heat flux was varied between 30 and 140 kW/m 2 so that the pseudo-critical point was located in the middle of the heated section at a given mass flux. The measurements were made at a pressure of 8.12 MPa, which corresponds to 110% of the critical pressure of CO 2 . The difference between the upward and downward flows was observed clearly. The heat transfer deterioration was observed in the downward flow through an annular subchannel over the region beyond the critical point. Several well-known correlations were evaluated against the experimental

  14. Immunization with avian metapneumovirus harboring chicken Fc induces higher immune responses.

    Science.gov (United States)

    Paudel, Sarita; Easwaran, Maheswaran; Jang, Hyun; Jung, Ho-Kyoung; Kim, Joo-Hun; Shin, Hyun-Jin

    2016-07-15

    In this study, we evaluated the immune responses of avian metapneumovirus harboring chicken Fc molecule. Stable Vero cells expressing chicken Fc chimera on its surface (Vero-cFc) were established, and we confirmed that aMPV grown in Vero-cFc incorporated host derived chimera Fc into the aMPV virions. Immunization of chicken with aMPV-cFc induced higher level of antibodies and inflammatory cytokines; (Interferon (IFN)-γ and Interleukin (IL)-1β) compared to those of aMPV. The increased levels of antibodies and inflammatory cytokines in chicken immunized with aMPV-cFc were statistically significantly (p<0.05) to that of aMPV and control. The aMPV-cFc group also generated the highest neutralizing antibody response. After challenges, chickens immunized with aMPV-cFc showed much less pathological signs in nasal turbinates and trachea so that we could confirm aMPV-cFc induced higher protection than that of aMPV. The greater ability of aMPV harboring chicken Fc to that of aMPV presented it as a possible vaccine candidate. Copyright © 2016 Elsevier B.V. All rights reserved.

  15. Dicty_cDB: FC-BS24 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available FC (Link to library) FC-BS24 (Link to dictyBase) - - - Contig-U16209-1 FC-BS24Z (Li...nk to Original site) - - FC-BS24Z 721 - - - - Show FC-BS24 Library FC (Link to library) Clone ID FC-BS24 (Link to dict...yBase) Atlas ID - NBRP ID - dictyBase ID - Link to Contig Contig-U16209-1 Original site URL http://dict...nce. 52 9e-12 4 BQ096846 |BQ096846.1 IfHdk00487 Ictalurus furcatus head kidney cDNA library Ict...N SA ;, mRNA sequence. 44 1e-10 4 BM438323 |BM438323.1 IpLvr01076 Liver cDNA library Ictalurus punctatus cDN

  16. Dicty_cDB: FC-IC0102 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available FC-IC (Link to library) FC-IC0102 (Link to dictyBase) - - - Contig-U16527-1 FC-IC01...02F (Link to Original site) FC-IC0102F 434 - - - - - - Show FC-IC0102 Library FC-IC (Link to library) Clone ...ID FC-IC0102 (Link to dictyBase) Atlas ID - NBRP ID - dictyBase ID - Link to Contig Contig-U16527-1 Original site URL http://dict... (bits) Value N AB088483 |AB088483.1 Dictyostelium discoideum gene for gamete and mating-type specific prote...oducing significant alignments: (bits) Value AB088483_1( AB088483 |pid:none) Dictyostelium discoideum gmsA g

  17. Dicty_cDB: FC-AA02 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available FC (Link to library) FC-AA02 (Link to dictyBase) - - - Contig-U16527-1 FC-AA02Z (Li...nk to Original site) - - FC-AA02Z 458 - - - - Show FC-AA02 Library FC (Link to library) Clone ID FC-AA02 (Link to dic...linum small subunit ribosomal RNA gene, partial sequence. 149 2e-47 2 AY179984 |AY179984.1 Uncultured alveo... CP000930_2283( CP000930 |pid:none) Heliobacterium modesticaldum Ic... 33 2.3 AP009386_1894( AP009386 |pid:none) Burkholderia multi... EU955514 |pid:none) Zea mays clone 1535262 hypothetica... 50 2e-05 BA000023_1285

  18. Representing or defecting ? : the pursuit of individual upward mobility in low status groups

    NARCIS (Netherlands)

    Bleeker, Dennis

    2010-01-01

    This dissertation investigated the conditions under which the individual upward mobility of mem-bers of low status groups is likely to succeed and when it is likely to meet resistance. In addition, it examines how upwardly mobile individuals can create such beneficial conditions. The results

  19. 34 CFR 645.1 - What is the Upward Bound Program?

    Science.gov (United States)

    2010-07-01

    ... participants the skills and motivation necessary to complete a program of secondary education and to enter and... the following three types of projects: (1) Regular Upward Bound projects. (2) Upward Bound Math and... Education Regulations of the Offices of the Department of Education (Continued) OFFICE OF POSTSECONDARY...

  20. Dual-Polarization Radar Observations of Upward Lightning-Producing Storms

    Science.gov (United States)

    Lueck, R.; Helsdon, J. H.; Warner, T.

    2013-12-01

    The Upward Lightning Triggering Study (UPLIGHTS) seeks to determine how upward lightning, which originates from the tips of tall objects, is triggered by nearby flash activity. As a component of this study we analyze standard and dual-polarization weather radar data. The Correlation Coefficient (CC) in particular can be used to identify and quantify the melting layer associated with storms that produce upward lightning. It has been proposed that positive charge generation due to aggregate shedding at the melting layer results in a positive charge region just above the cloud base. This positive charge region may serve as a positive potential well favorable for negative leader propagation, which initiate upward positive leaders from tall objects. We characterize the horizontal coverage, thickness and height of the melting layer in addition to cloud base heights when upward lightning occurs to determine trends and possible threshold criteria relating to upward lightning production. Furthermore, we characterize storm type and morphology using relevant schemes as well as precipitation type using the Hydrometer Classification Algorithm (HCA) for upward lightning-producing storms. Ice-phase hydrometeors have been shown to be a significant factor in thunderstorm electrification. Only a small fraction of storms produce upward lightning, so null cases will be examined and compared as well.

  1. Identification of Fc Gamma Receptor Glycoforms That Produce Differential Binding Kinetics for Rituximab.

    Science.gov (United States)

    Hayes, Jerrard M; Frostell, Asa; Karlsson, Robert; Müller, Steffen; Martín, Silvia Míllan; Pauers, Martin; Reuss, Franziska; Cosgrave, Eoin F; Anneren, Cecilia; Davey, Gavin P; Rudd, Pauline M

    2017-10-01

    Fc gamma receptors (FcγR) bind the Fc region of antibodies and therefore play a prominent role in antibody-dependent cell-based immune responses such as ADCC, CDC and ADCP. The immune effector cell activity is directly linked to a productive molecular engagement of FcγRs where both the protein and glycan moiety of antibody and receptor can affect the interaction and in the present study we focus on the role of the FcγR glycans in this interaction. We provide a complete description of the glycan composition of Chinese hamster ovary (CHO) expressed human Fcγ receptors RI (CD64), RIIa Arg131/His131 (CD32a), RIIb (CD32b) and RIIIa Phe158/Val158 (CD16a) and analyze the role of the glycans in the binding mechanism with IgG. The interactions of the monoclonal antibody rituximab with each FcγR were characterized and we discuss the CHO-FcγRIIIa Phe158/Val158 and CHO-FcγRI interactions and compare them to the equivalent interactions with human (HEK293) and murine (NS0) produced receptors. Our results reveal clear differences in the binding profiles of rituximab, which we attribute in each case to the differences in host cell-dependent FcγR glycosylation. The glycan profiles of CHO expressed FcγRI and FcγRIIIa Phe158/Val158 were compared with the glycan profiles of the receptors expressed in NS0 and HEK293 cells and we show that the glycan type and abundance differs significantly between the receptors and that these glycan differences lead to the observed differences in the respective FcγR binding patterns with rituximab. Oligomannose structures are prevalent on FcγRI from each source and likely contribute to the high affinity rituximab interaction through a stabilization effect. On FcγRI and FcγRIIIa large and sialylated glycans have a negative impact on rituximab binding, likely through destabilization of the interaction. In conclusion, the data show that the IgG1-FcγR binding kinetics differ depending on the glycosylation of the FcγR and further support a

  2. Studies of vertical fluxes of horizontal momentum in the lower atmosphere using the MU-radar

    Directory of Open Access Journals (Sweden)

    F. S. Kuo

    2008-11-01

    Full Text Available We study the momentum flux of the atmospheric motions in the height ranges between 6 and 22 km observed using the MU radar at Shigaraki in Japan during a 3 day period in January 1988. The data were divided by double Fourier transformation into data set of waves with downward- phase- velocity and data set of waves with upward-phase-velocity for independent momentum flux calculation. The result showed that both the 72 h averaged upward flux and downward flux of zonal momentum were negative at nearly each height, meaning that the upward flux was dominated by westward propagating waves while the downward flux was dominated by eastward propagating waves. The magnitude of the downward flux was approximately a factor of 1.5 larger than the upward flux for waves in the 2~7 h and 7~24 h period bands, and about equal to the upward flux in the 10–30 min and 30 min–2 h period bands. It is also observed that the vertical flux of zonal momentum tended to be small in each frequency band at the altitudes below the jet maximum (10~12 km, and the flux increased toward more negative values to reach a negative maximum at some altitude well above the jet maximum. Daily averaged flux showed tremendous variation: The 1st 24 h (quiet day was relatively quiet, and the fluxes of the 2nd and 3rd 24 h (active days increased sharply. Moreover, the upward fluxes of zonal momentum below 17 km in the quiet day for each period band (10~30 min, 30 min~2 h, 2~7 h, and 7~24 h were dominantly positive, while the corresponding downward fluxes were dominantly negative, meaning that the zonal momentum below 17 km in each period band under study were dominantly eastward (propagating along the mean wind. In the active days, both the upward fluxes and downward fluxes in each frequency band were dominantly negative throughout the whole altitude range 6.1–18.95 km.

  3. Assessing the Heterogeneity of the Fc-Glycan of a Therapeutic Antibody Using an engineered FcγReceptor IIIa-Immobilized Column.

    Science.gov (United States)

    Kiyoshi, Masato; Caaveiro, Jose M M; Tada, Minoru; Tamura, Hiroko; Tanaka, Toru; Terao, Yosuke; Morante, Koldo; Harazono, Akira; Hashii, Noritaka; Shibata, Hiroko; Kuroda, Daisuke; Nagatoishi, Satoru; Oe, Seigo; Ide, Teruhiko; Tsumoto, Kouhei; Ishii-Watabe, Akiko

    2018-03-02

    The N-glycan moiety of IgG-Fc has a significant impact on multifaceted properties of antibodies such as in their effector function, structure, and stability. Numerous studies have been devoted to understanding its biological effect since the exact composition of the Fc N-glycan modulates the magnitude of effector functions such as the antibody-dependent cell mediated cytotoxicity (ADCC), and the complement-dependent cytotoxicity (CDC). To date, systematic analyses of the properties and influence of glycan variants have been of great interest. Understanding the principles on how N-glycosylation modulates those properties is important for the molecular design, manufacturing, process optimization, and quality control of therapeutic antibodies. In this study, we have separated a model therapeutic antibody into three fractions according to the composition of the N-glycan by using a novel FcγRIIIa chromatography column. Notably, Fc galactosylation was a major factor influencing the affinity of IgG-Fc to the FcγRIIIa immobilized on the column. Each antibody fraction was employed for structural, biological, and physicochemical analysis, illustrating the mechanism by which galactose modulates the affinity to FcγRIIIa. In addition, we discuss the benefits of the FcγRIIIa chromatography column to assess the heterogeneity of the N-glycan.

  4. Human IgG4 binds to IgG4 and conformationally altered IgG1 via Fc-Fc interactions

    NARCIS (Netherlands)

    Rispens, Theo; Ooievaar-de Heer, Pleuni; Vermeulen, Ellen; Schuurman, Janine; van der Neut Kolfschoten, Marijn; Aalberse, Rob C.

    2009-01-01

    The Fc fragment of IgG4 can interact with the Fc fragment of another IgG molecule. This interaction is a confounding factor when measuring IgG4 rheumatoid factor levels. Recently, we demonstrated that half-molecules of IgG4 can exchange to form a bispecific Ab. We expected these two phenomena to be

  5. A case study of lightning attachment to flat ground showing multiple unconnected upward leaders

    Science.gov (United States)

    Cummins, Kenneth L.; Krider, E. Philip; Olbinski, Mike; Holle, Ronald L.

    2018-04-01

    On 10 July 2015, a cloud-to-ground (CG) lightning flash that produced two ground terminations was photographed from inside the safety of a truck in southern New Mexico. An analysis of archived NLDN data verified that this was a two-stroke flash, and a close-up view of the first stroke shows that it also initiated at least 12 unconnected, upward leaders (or "streamers") near the ground termination. No unconnected upward leaders were seen near the second ground attachment. After combining an analysis of the photograph with information provided by the NLDN, we infer that the first stroke was of negative (normal) polarity, had modest peak current, and struck about 460 m (± 24%) from the camera. Attachment occurred when an upward-propagating positive leader reached an inferred height of about 21 m above local ground. The second stroke struck ground about 740 m from the camera, and the height of its attachment leader is estimated to be 15 m. The estimated lengths of the unconnected upward leaders in the two-dimensional (2-D) plane of the first stroke range from 2 to 8 m, and all appear to be located within 15 m (2-D) of the main ground termination, with 24% uncertainty. Many of the unconnected upward leaders (inferred to be positive) exhibit multiple upward branches, and most of those branches have upward-directed forks or splits at their ends. This is the first report showing such extensive branching for positive upward leaders in natural lightning strikes to ground. None of the upward leaders can be seen to emanate from the tops of tall, isolated, or pointed objects on the ground, but they likely begin on small plants and rocks, or flat ground. In terms of lightning safety, this photo demonstrates that numerous upward leaders can be produced near a lightning strike point and have the potential to damage or cause injury at more than one specific point on the ground.

  6. Monoclonal antibodies and Fc fragments for treating solid tumors

    Directory of Open Access Journals (Sweden)

    Eisenbeis AM

    2012-01-01

    Full Text Available Andrea M Eisenbeis, Stefan J GrauDepartment of Neurosurgery, University Hospital of Cologne, Cologne, GermanyAbstract: Advances in biotechnology, better understanding of pathophysiological processes, as well as the identification of an increasing number of molecular markers have facilitated the use of monoclonal antibodies and Fc fragments in various fields in medicine. In this context, a rapidly growing number of these substances have also emerged in the field of oncology. This review will summarize the currently approved monoclonal antibodies used for the treatment of solid tumors with a focus on their clinical application, biological background, and currently ongoing trials.Keywords: targeted therapy, monoclonal antibodies, cancer, biological therapy

  7. Integrated Design for Geoscience Education with Upward Bound Students

    Science.gov (United States)

    Cartwright, T. J.; Hogsett, M.; Ensign, T. I.; Hemler, D.

    2009-05-01

    Capturing the interest of our students is imperative to expand the conduit of future Earth scientists in the United States. According to the Rising Above the Gathering Storm report (2005), we must increase America's talent pool by improving K-12 mathematics and science education. Geoscience education is uniquely suited to accomplish this goal, as we have become acutely aware of our sensitivity to the destructive forces of nature. The educational community must take advantage of this heightened awareness to educate our students and ensure the next generation rebuilds the scientific and technological base on which our society rests. In response to these concerns, the National Science Foundation advocates initiatives in Geoscience Education such as IDGE (Integrated Design for Geoscience Education), which is an inquiry-based geoscience program for Upward Bound (UB) students at Marshall University in Huntington, West Virginia. The UB program targets low-income under-represented students for a summer academic-enrichment program. IDGE builds on the mission of UB by encouraging underprivileged students to investigate science and scientific careers. During the two year project, high school students participated in an Environmental Inquiry course utilizing GLOBE program materials and on-line learning modules developed by geoscience specialists in land cover, soils, hydrology, phenology, and meteorology. Students continued to an advanced course which required IDGE students to collaborate with GLOBE students from Costa Rica. The culmination of this project was an educational expedition in Costa Rica to complete ecological field studies, providing first-hand knowledge of the international responsibility we have as scientists and citizens of our planet. IDGE was designed to continuously serve educators and students. By coordinating initiatives with GLOBE headquarters and the GLOBE country community, IDGE's efforts have yielded multiple ways in which to optimize positive

  8. An experimental comparison between forced convection burn-out in freon 12 flowing vertically upwards through uniformly and non-uniformly heated round tubes

    International Nuclear Information System (INIS)

    Stevens, G.F.; Elliott, D.F.; Wood, R.W.

    1965-05-01

    Some correlations of forced convection burn-out data are based on the approximate linearity of the relationship between burn-out heat flux and the channel-averaged quality at the burn-out point. These correlations perform satisfactorily on data obtained from uniformly heated configurations. Therefore the further inference is sometimes made that the burn-out heat flux is uniquely related to the quality, and that the burn-out in non-uniformly heated configurations can be calculated from measurements made with uniform heating. This report presents burn-out data for Freon 12 flowing vertically upwards through both uniformly and non-uniformly heated round tubes. This data shows that the quality at burn-out does depend on the heat flux profile, and that the inference mentioned above is not justified. (author)

  9. Enhanced antibody-dependent cellular phagocytosis by chimeric monoclonal antibodies with tandemly repeated Fc domains.

    Science.gov (United States)

    Nagashima, Hiroaki; Ootsubo, Michiko; Fukazawa, Mizuki; Motoi, Sotaro; Konakahara, Shu; Masuho, Yasuhiko

    2011-04-01

    We previously reported that chimeric monoclonal antibodies (mAbs) with tandemly repeated Fc domains, which were developed by introducing tandem repeats of Fc domains downstream of 2 Fab domains, augmented binding avidities for all Fcγ receptors, resulting in enhanced antibody (Ab)-dependent cellular cytotoxicity. Here we investigated regarding Ab-dependent cellular phagocytosis (ADCP) mediated by these chimeric mAbs, which is considered one of the most important mechanisms that kills tumor cells, using two-color flow cytometric methods. ADCP mediated by T3-Ab, a chimeric mAb with 3 tandemly repeated Fc domains, was 5 times more potent than that by native anti-CD20 M-Ab (M-Ab hereafter). Furthermore, T3-Ab-mediated ADCP was resistant to competitive inhibition by intravenous Ig (IVIG), although M-Ab-mediated ADCP decreased in the presence of IVIG. An Fcγ receptor-blocking study demonstrated that T3-Ab mediated ADCP via both FcγRIA and FcγRIIA, whereas M-Ab mediated ADCP exclusively via FcγRIA. These results suggest that chimeric mAbs with tandemly repeated Fc domains enhance ADCP as well as ADCC, and that Fc multimerization may significantly enhance the efficacy of therapeutic Abs. Copyright © 2010 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

  10. A Peptide-Fc Opsonin with Pan-Amyloid Reactivity

    Directory of Open Access Journals (Sweden)

    James S. Foster

    2017-09-01

    Full Text Available There is a continuing need for therapeutic interventions for patients with the protein misfolding disorders that result in systemic amyloidosis. Recently, specific antibodies have been employed to treat AL amyloidosis by opsonizing tissue amyloid deposits thereby inducing cell-mediated dissolution and organ improvement. To develop a pan-amyloid therapeutic agent, we have produced an Fc-fusion product incorporating a peptide, p5, which binds many if not all forms of amyloid. This protein, designated Fcp5, expressed in mammalian cells, forms the desired bivalent dimer structure and retains pan-amyloid reactivity similar to the p5 peptide as measured by immunosorbent assays, immunohistochemistry, surface plasmon resonance, and pulldown assays using radioiodinated Fcp5. Additionally, Fcp5 was capable of opsonizing amyloid fibrils in vitro using a pH-sensitive fluorescence assay of phagocytosis. In mice,125 I-labeled Fcp5 exhibited an extended serum circulation time, relative to the p5 peptide. It specifically bound AA amyloid deposits in diseased mice, as evidenced by biodistribution and microautoradiographic methods, which coincided with an increase in active, Iba-1-positive macrophages in the liver at 48 h postinjection of Fcp5. In healthy mice, no specific tissue accumulation was observed. The data indicate that polybasic, pan-amyloid-targeting peptides, in the context of an Fc fusion, can yield amyloid reactive, opsonizing reagents that may serve as next-generation immunotherapeutics.

  11. 40 CFR Table 25 to Subpart G of... - Effective Column Diameter (Fc)

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 9 2010-07-01 2010-07-01 false Effective Column Diameter (Fc) 25 Table..., Table 25 Table 25 to Subpart G of Part 63—Effective Column Diameter (Fc) Column type Fc (feet) 9-inch by 7-inch built-up columns 1.1 8-inch-diameter pipe columns 0.7 No construction details known 1.0 ...

  12. Comparative studies on Fc receptors for IgG on resting and activated T lymphocytes

    International Nuclear Information System (INIS)

    Hueckel, C.; Jensen, H.L.; Rychly, J.; Sandor, M.; Erdei, A.; Gergely, J.

    1986-01-01

    Fc-receptors for IgG (FcγR) on resting (i.e. freshly prepared) and mitogen (Con A) or alloantigen-activated mouse spleen T cells were compared using binding of different markers such as 125 I-labelled immune complexes, 125 I-labelled anti FcγR monoclonal antibody, FITC-labelled aggr. IgG and sheep erythrocytes covered with specific antibody (EA rosetting). C3b receptors were detected by rosetting with sheep erythrocytes covered with antibody and complement (EAC rosetting). The electrophoretic mobility of the cells without or after binding of aggr. IgG was also tested. Differences between resting and activated T cells were found: (1) After activation of T cells by mitogen or alloantigen, a proportion of FcγR-positive cells increased two to four times. (2) FcγR number per FcγR-positive cell seemed to be higher on activated then on resting cells. (3) FcγR-positive resting cells did not shed their FcγR upon incubation at 4 0 C followed by incubation at 37 0 C, but FcγR-positive activated cells shed a remarkable proportion of their FcγR on the same conditions. (4) Binding of aggr. IgG caused a decrease of electrophoretic mobility of activated but not resting cells. (5) FcγR-positive resting cells were also C3b receptor-positive, whereas FcγR-positive activated cells had no detectable C3b receptors. (author)

  13. Prophylactic anti-D preparations display variable decreases in Fc-fucosylation of anti-D.

    Science.gov (United States)

    Kapur, Rick; Della Valle, Luciana; Verhagen, Onno J H M; Hipgrave Ederveen, Agnes; Ligthart, Peter; de Haas, Masja; Kumpel, Belinda; Wuhrer, Manfred; van der Schoot, C Ellen; Vidarsson, Gestur

    2015-03-01

    RhIG is obtained from hyperimmunized healthy anti-D donors (HIDs) boosted with D+ red blood cells (RBCs). One hypothesis for its mechanism of action is fast clearance of opsonized D+ RBCs through Fcγ receptor (FcγR)III. Levels of immunoglobulin (Ig)G Fc-fucosylation influence interactions with FcγRIII, with less Fc-fucosylation strengthening the interaction. Anti-D IgG1 Fc-glycosylation patterns in 93 plasma samples from 28 male and 28 female Dutch HIDs and RhIG were analyzed with mass spectrometry. The Fc-glycosylation profiles of HIDs were evaluated with regard to their immunization history. HID sera demonstrated clearly lowered anti-D Fc-fucosylation compared to normal IgG fucosylation (93%); this was more pronounced for female than for male HIDs (47% vs. 65%, p = 0.001). RhIG preparations from seven manufacturers varied greatly in the level of Fc-fucosylation (56%-91%). The level of fucosylation slightly increased upon repeated immunization, although it remained fairly constant over time. The RhIG from the different manufacturers all demonstrated increased Fc-galactosylation (64%-82%) compared to total IgG (38%-51%). RhIG preparations vary in Fc-fucosylation and all demonstrate increased galactosylation. Despite not knowing the exact working mechanism, immunoprophylaxis could perhaps be optimized by selection of donors whose anti-D have low amounts of Fc-fucose, to increase the clearance activity of anti-D preparations, as well as high amounts of galactosylation, for anti-inflammatory effects. Implementing a biologic assay in the standardization of RhIG preparations might be considered. © 2014 AABB.

  14. Induction of functional Fc receptors in P388 leukemia cells. Requirement for multiple differentiation signals.

    Science.gov (United States)

    Cohen, D A; Stotelmyer, N L; Kaplan, A M

    1985-04-01

    The development of functional Fc receptors (FcR) during induced differentiation with the tumor promoter, phorbol myristate acetate (PMA), was studied in the murine tumor cell line, P388. PMA induced the appearance of FcR on the membranes of P388 cells as indicated by the binding of IgG-coated sheep red blood cells (IgG-SRBC). Concentrations of PMA as low as 1 ng/ml were sufficient to induce the expression of FcR as well as to inhibit cellular division and to induce adherence in the P388 tumor cell line; however, optimal FcR induction occurred at PMA concentrations of 10-100 ng/ml. Immunofluorescent analysis with heat-aggregated myeloma proteins indicated that PMA induced FcR which were capable of binding IgG2a and IgG2b immunoglobulins, but not IgG1. Adherence to a substratum was determined to be a second required signal for expression of FcR, since PMA induction of P388 tumor cells in teflon dishes failed to fully develop FcR and adherence of P388 cells to poly-L-lysine-coated culture dishes in the absence of PMA was insufficient for FcR expression. FcR which appeared after PMA induction were non-functional in the sense that membrane-bound IgG-SRBC were not ingested to any significant extent by the tumor cells. However, if FcR induction occurred in the presence conA-induced rat spleen cell culture supernatants, phagocytosis of membrane-bound erythrocytes occurred. These findings suggest that for the expression of FcR which are capable of particle internalization, at least three identifiable membrane-transmitted signals are required during differentiation.

  15. Structural characterization of the Man5 glycoform of human IgG3 Fc

    Energy Technology Data Exchange (ETDEWEB)

    Shah, Ishan S.; Lovell, Scott; Mehzabeen, Nurjahan; Battaile, Kevin P.; Tolbert, Thomas J. (Kansas); (HWMRI)

    2017-12-01

    Immunoglobulin G (IgG) consists of four subclasses in humans: IgG1, IgG2, IgG3 and IgG4, which are highly conserved but have unique differences that result in subclass-specific effector functions. Though IgG1 is the most extensively studied IgG subclass, study of other subclasses is important to understand overall immune function and for development of new therapeutics. When compared to IgG1, IgG3 exhibits a similar binding profile to Fcγ receptors and stronger activation of complement. All IgG subclasses are glycosylated at N297, which is required for Fcγ receptor and C1q complement binding as well as maintaining optimal Fc conformation. We have determined the crystal structure of homogenously glycosylated human IgG3 Fc with a GlcNAc2Man5 (Man5) high mannose glycoform at 1.8 Å resolution and compared its structural features with published structures from the other IgG subclasses. Although the overall structure of IgG3 Fc is similar to that of other subclasses, some structural perturbations based on sequence differences were revealed. For instance, the presence of R435 in IgG3 (and H435 in the other IgG subclasses) has been implicated to result in IgG3-specific properties related to binding to protein A, protein G and the neonatal Fc receptor (FcRn). The IgG3 Fc structure helps to explain some of these differences. Additionally, protein-glycan contacts observed in the crystal structure appear to correlate with IgG3 affinity for Fcγ receptors as shown by binding studies with IgG3 Fc glycoforms. Finally, this IgG3 Fc structure provides a template for further studies aimed at engineering the Fc for specific gain of function.

  16. Dicty_cDB: FC-AJ15 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available FC (Link to library) FC-AJ15 (Link to dictyBase) - G01152 DDB0232964 Contig-U16520-...to library) Clone ID FC-AJ15 (Link to dictyBase) Atlas ID - NBRP ID G01152 dictyBase ID DDB0232964 Link to C...ontig Contig-U16520-1 Original site URL http://dictycdb.biol.tsukuba.ac.jp/CSM/FC...KIEFPLPDIKTKRKIFEI HTAKMNLSEDVNLEEFVMSKDDLSGADIKAICTESGLLALRERRMRVTHTDFKKAKEKVL YRKTAGAPEGLYM*kkknqnqk Trans...vih*qlviwrrlsmxitpschqp*tralcpyhvfv--- ---ELLNQLDGFDASTDVKVIMATNRIETLDPALIRPGRIDRKIEFPLPDIKTKRKIFEI HTAKMNLSEDVNLEEFVMSKDDLSGADIKAICT

  17. FcεRI γ-Chain Negatively Modulates Dectin-1 Responses in Dendritic Cells

    Directory of Open Access Journals (Sweden)

    Yi-Gen Pan

    2017-10-01

    Full Text Available The inhibitory effect of immunoreceptor tyrosine-based activation motif (ITAM-containing adapters DAP12 and FcεRI γ-chain (FcRγ has been found in many immune functions. Herein, we have further explored the role of these adapters in C-type lectin receptors response. We identified that FcRγ, but not DAP12, could negatively regulate the Dectin-1 responses in dendritic cells (DCs. Loss of FcRγ or both DAP12 and FcRγ enhanced the maturation and cytokine production in DCs upon Dectin-1 activation compared to normal cells, whereas DCs lacking only DAP12 showed little changes. In addition, increments of T cell activation and T helper 17 polarization induced by FcRγ-deficient DCs were observed both in vitro and in vivo. Examining the Dectin-1 signaling, we revealed that the activations of several signaling molecules were augmented in FcRγ-deficient DCs stimulated with Dectin-1 ligands. Furthermore, we demonstrated that the association of phosphatases SHP-1 and PTEN with FcRγ may contribute to the negative regulation of FcRγ in Dectin-1 activation in DCs. These results extend the inhibitory effect of ITAM-containing adapters to Dectin-1 response in immune functions, even though Dectin-1 contains an ITAM-like intracellular domain. According to the role of Dectin-1 in responding to microbes and tumor cells, our finding may have applications in the development of vaccine and cancer therapy.

  18. CFD Study of Deteriorated Turbulent Heat Transfer in Upward Flow

    International Nuclear Information System (INIS)

    Nietiadi, Yohanes Setiawan; Lee, Jeong Ik; Addad, Yacine

    2014-01-01

    Transfer (DTHT) regime as heat flux becomes higher under low cooling flow environment such as natural circulation operation in the past research works. Therefore, the unique behavior of the gas properties in the DTHT regime should be investigated

  19. Preparation of TiC/Ni3Al Composites by Upward Melt Infiltration

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    TiC/Ni3Al composites have been prepared using upward infiltration method. The densificstion was performed by both Ni3Al melt filling and TiC sintering during the infiltration. The dissolution of TiC in liquid Ni3Al has been evidenced by finding Ni3(Al,Ti)C after fast cooling in the TiC/Ni3Al composites. The dissolution may be responsible for the infiltration and sintering. Compared with downward infiltration, the upward infiltration brought about higher strength and fracture toughness and shorter infiltration time. TiC/20 vol. pct Ni3Al composite processed by upward infiltration had a flexural strength of 1476 Mpa with a statistic Weibull modulus of 20.2 and a fracture toughness of 20.4 Mpa(m). Better mechanical properties may be attributed to melt unidirectional movement in upward infiltration.

  20. CT-FC: more Comprehensive Traversal Focused Crawler

    Directory of Open Access Journals (Sweden)

    NFN Kuspriyanto

    2012-03-01

    Full Text Available In todays world, people depend more on the WWW information, including professionals who have to analyze the data according their domain to maintain and improve their business. A data analysis would require information that is comprehensive and relevant to their domain. Focused crawler as a topical based Web indexer agent is used to meet this applications information need. In order to increase the precision, focused crawler face the problem of low recall. The study on WWW hyperlink structure characteristics indicates that many Web documents are not strong connected but through co-citation & co-reference. Conventional focused crawler that uses forward crawling strategy could not visit the documents in these characteristics. This study proposes a more comprehensive traversal framework. As a proof, CT-FC (a focused crawler with the new traversal framework ran on DMOZ data that is representative to WWW characteristics. The results show that this strategy can increase the recall significantly.

  1. Churn-annular flow pattern transition in a vertical upward gas-liquid two-phase flow in various conduits

    International Nuclear Information System (INIS)

    Takenaka, Nobuyuki; Ueda, Tadanobu; Asano, Hitoshi

    2008-01-01

    Void fraction was measured by neutron radiography for a vertical upward gas-water two-phase flow in a concentric annular tube with and with out a spacer, 4x4 rod bundle with and without a spacer and a tight rod bundle with and without a wrapping wire for various gas and liquid flow rates. The flow patterns of these two-phase flows were determined by the Mishima-Ishii flow pattern map and void fraction was calculated by the Ishii's drift flux model. The predicted values were compared with the experimental results. The void fraction was well predicted by the Mishima-Ishii flow pattern map and the Ishii's drift flux model except the annular flow region with void fraction lower than 0.8 for conduits with small equivalent diameter. A new churn-annular flow pattern transition condition of the void fraction equal to 0.8 was added. The void fraction for the present experimental condition was successful predicted with the new transition model. (author)

  2. A study on the upward and downward facing pool boiling heat transfer characteristics of graphene-modified surface

    International Nuclear Information System (INIS)

    Kim, Ji Hoon; Ahn, Ho Seon; Kim, Ji Min

    2016-01-01

    Recently, graphene, carbon in two dimensions, were highlighted as a good heat transfer materials, according to its high thermal conductivity. Lateral conduction and water absorption into the structure helped graphene films to inhibit the formation of hot spots, which means increasing of critical heat flux (CHF) and boiling heat transfer coefficient (BHTC) performances. In this study, we report a promising increase of CHF and BHTC results with 2D graphene films. Furthermore, we tried to observe bubble behavior via high-speed visualization to investigate a relationship between bubble behavior and pool boiling performances in downward facing boiling. The effect of graphene film coating on the pool boiling performances of upward and downward facing heater surface were examined. 2D- and 3D- graphene film showed good enhancement results on the CHF (by 111% and 60%) and BHTC (by 40% and 20-25%) performances. Bubble behavior change was significant factor on the CHF and BHTC performances in downward facing boiling. The amount of evaporation heat flux was calculated from the velocity, bubble diameter, frequency, orientation angle and superheat that the post-products of the high-speed visualization

  3. Investigation of forced convection heat transfer of supercritical pressure water in a vertically upward internally ribbed tube

    International Nuclear Information System (INIS)

    Wang Jianguo; Li Huixiong; Guo Bin; Yu Shuiqing; Zhang Yuqian; Chen Tingkuan

    2009-01-01

    In the present paper, the forced convection heat transfer characteristics of water in a vertically upward internally ribbed tube at supercritical pressures were investigated experimentally. The six-head internally ribbed tube is made of SA-213T12 steel with an outer diameter of 31.8 mm and a wall thickness of 6 mm and the mean inside diameter of the tube is measured to be 17.6 mm. The experimental parameters were as follows. The pressure at the inlet of the test section varied from 25.0 to 29.0 MPa, and the mass flux was from 800 to 1200 kg/(m 2 s), and the inside wall heat flux ranged from 260 to 660 kW/m 2 . According to experimental data, the effects of heat flux and pressure on heat transfer of supercritical pressure water in the vertically upward internally ribbed tube were analyzed, and the characteristics and mechanisms of heat transfer enhancement, and also that of heat transfer deterioration, were also discussed in the so-called large specific heat region. The drastic changes in thermophysical properties near the pseudocritical points, especially the sudden rise in the specific heat of water at supercritical pressures, may result in the occurrence of the heat transfer enhancement, while the covering of the heat transfer surface by fluids lighter and hotter than the bulk fluid makes the heat transfer deteriorated eventually and explains how this lighter fluid layer forms. It was found that the heat transfer characteristics of water at supercritical pressures were greatly different from the single-phase convection heat transfer at subcritical pressures. There are three heat transfer modes of water at supercritical pressures: (1) normal heat transfer, (2) deteriorated heat transfer with low HTC but high wall temperatures in comparison to the normal heat transfer, and (3) enhanced heat transfer with high HTC and low wall temperatures in comparison to the normal heat transfer. It was also found that the heat transfer deterioration at supercritical pressures was

  4. Multiple Plasmodium falciparum erythrocyte membrane protein 1 variants per genome can bind IgM via its Fc fragment Fcμ

    DEFF Research Database (Denmark)

    Jeppesen, Anine; Ditlev, Sisse Bolm; Soroka, Vladyslav

    2015-01-01

    with severe clinical manifestations, such as cerebral malaria in children and placental malaria in pregnant women. PfEMP1 that can bind the Fc part of IgM (Fcμ) characterizes one such type, although the functional significance of this IgM binding to PfEMP1 remains unclear. In this study, we report...... resemble the rosette-mediating and IgM-binding PfEMP1 HB3VAR06, but none of them mediated formation of rosettes. We could map the capacity for Fc-specific IgM binding to DBLε domains near the C terminus for three of the four PfEMP1 proteins tested. Our study provides new evidence regarding Fc...

  5. Investigating the Interaction between the Neonatal Fc Receptor and Monoclonal Antibody Variants by Hydrogen/Deuterium Exchange Mass Spectrometry

    DEFF Research Database (Denmark)

    Jensen, Pernille Foged; Larraillet, Vincent; Schlothauer, Tilman

    2015-01-01

    The recycling of immunoglobulins by the neonatal Fc receptor (FcRn) is of crucial importance in the maintenance of antibody levels in plasma and is responsible for the long half-lives of endogenous and recombinant monoclonal antibodies. From a therapeutic point of view there is great interest...... in understanding and modulating the IgG-FcRn interaction to optimize antibody pharmacokinetics and ultimately improve efficacy and safety. Here we studied the interaction between a full-length human IgG1 and human FcRn via hydrogen/deuterium exchange mass spectrometry and targeted electron transfer dissociation...... to map sites perturbed by binding on both partners of the IgG-FcRn complex. Several regions in the antibody Fc region and the FcRn were protected from exchange upon complex formation, in good agreement with previous crystallographic studies of FcRn in complex with the Fc fragment. Interestingly, we found...

  6. Identification of antibody glycosylation structures that predict monoclonal antibody Fc-effector function.

    Science.gov (United States)

    Chung, Amy W; Crispin, Max; Pritchard, Laura; Robinson, Hannah; Gorny, Miroslaw K; Yu, Xiaojie; Bailey-Kellogg, Chris; Ackerman, Margaret E; Scanlan, Chris; Zolla-Pazner, Susan; Alter, Galit

    2014-11-13

    To determine monoclonal antibody (mAb) features that predict fragment crystalizable (Fc)-mediated effector functions against HIV. Monoclonal antibodies, derived from Chinese hamster ovary cells or Epstein-Barr virus-immortalized mouse heteromyelomas, with specificity to key regions of the HIV envelope including gp120-V2, gp120-V3 loop, gp120-CD4(+) binding site, and gp41-specific antibodies, were functionally profiled to determine the relative contribution of the variable and constant domain features of the antibodies in driving robust Fc-effector functions. Each mAb was assayed for antibody-binding affinity to gp140(SR162), antibody-dependent cellular cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP) and for the ability to bind to FcγRIIa, FcγRIIb and FcγRIIIa receptors. Antibody glycan profiles were determined by HPLC. Neither the specificity nor the affinity of the mAbs determined the potency of Fc-effector function. FcγRIIIa binding strongly predicted ADCC and decreased galactose content inversely correlated with ADCP, whereas N-glycolylneuraminic acid-containing structures exhibited enhanced ADCP. Additionally, the bi-antenary glycan arm onto which galactose was added predicted enhanced binding to FcγRIIIa and ADCC activity, independent of the specificity of the mAb. Our studies point to the specific Fc-glycan structures that can selectively promote Fc-effector functions independently of the antibody specificity. Furthermore, we demonstrated antibody glycan structures associated with enhanced ADCP activity, an emerging Fc-effector function that may aid in the control and clearance of HIV infection.

  7. Heat Transfer Characteristics for an Upward Flowing Supercritical Pressure CO{sub 2} in a Vertical Circular Tube

    Energy Technology Data Exchange (ETDEWEB)

    Kang, Deog Ji

    2008-02-15

    The SCWR(Super Critical Water-cooled Reactor) is one of the feasible options for the 4th generation nuclear power plant, which is being pursued by an international collaborative organization, the Gen IV International Forum(GIF). The major advantages of the SCWR include a high thermal efficiency and a maximum use of the existing technologies. In the SCWR, the coolant(water) of a supercritical pressure passes the pseudo-critical temperature as it flows upward through the sub-channels of the fuel assemblies. At certain conditions a heat transfer deterioration occurs near the pseudo-critical temperature and it may cause an excessive rise of the fuel surface temperature. Therefore, an accurate estimation of the heat transfer coefficient is necessary for the thermal-hydraulic design of the reactor core. A test facility, SPHINX(Supercritical Pressure Heat Transfer Investigation for the Next Generation), dedicated to produce heat transfer data and study flow characteristics, uses supercritical pressure CO{sub 2} as a surrogate medium to take advantage of the relatively low critical temperature and pressure: and similar physical properties with water. The produced data includes the temperature of the heating surface and the heat transfer coefficient at varying mass fluxes, heat fluxes, and operating pressures. The test section is a circular tube of ID 6.32 mm: it is almost the same as the hydraulic diameter of the sub-channel in the conceptional design presented by KAERI. The test range of the mass flux is 285 to 1200 kg/m{sup 2}s and the maximum heat flux is 170 kW/m{sup 2}. The tests were mainly performed for an inlet pressure of 8.12 MPa which is 1.1 times of critical pressure. With the test results of the wall temperature and the heat transfer coefficient, effects of mass flux, heat flux, inlet pressure, and the tube diameter on the heat transfer were studied. And the test results were compared with the existing correlations of the Nusselt number. In addition, New

  8. 34 CFR 645.13 - What additional services do Upward Bound Math and Science Centers provide and how are they...

    Science.gov (United States)

    2010-07-01

    ... 34 Education 3 2010-07-01 2010-07-01 false What additional services do Upward Bound Math and... Program? § 645.13 What additional services do Upward Bound Math and Science Centers provide and how are... provided under § 645.11(b), an Upward Bound Math and Science Center must provide— (1) Intensive instruction...

  9. Surface Flux Modeling for Air Quality Applications

    Directory of Open Access Journals (Sweden)

    Limei Ran

    2011-08-01

    Full Text Available For many gasses and aerosols, dry deposition is an important sink of atmospheric mass. Dry deposition fluxes are also important sources of pollutants to terrestrial and aquatic ecosystems. The surface fluxes of some gases, such as ammonia, mercury, and certain volatile organic compounds, can be upward into the air as well as downward to the surface and therefore should be modeled as bi-directional fluxes. Model parameterizations of dry deposition in air quality models have been represented by simple electrical resistance analogs for almost 30 years. Uncertainties in surface flux modeling in global to mesoscale models are being slowly reduced as more field measurements provide constraints on parameterizations. However, at the same time, more chemical species are being added to surface flux models as air quality models are expanded to include more complex chemistry and are being applied to a wider array of environmental issues. Since surface flux measurements of many of these chemicals are still lacking, resistances are usually parameterized using simple scaling by water or lipid solubility and reactivity. Advances in recent years have included bi-directional flux algorithms that require a shift from pre-computation of deposition velocities to fully integrated surface flux calculations within air quality models. Improved modeling of the stomatal component of chemical surface fluxes has resulted from improved evapotranspiration modeling in land surface models and closer integration between meteorology and air quality models. Satellite-derived land use characterization and vegetation products and indices are improving model representation of spatial and temporal variations in surface flux processes. This review describes the current state of chemical dry deposition modeling, recent progress in bi-directional flux modeling, synergistic model development research with field measurements, and coupling with meteorological land surface models.

  10. Generation and Characterization of an IgG4 Monomeric Fc Platform.

    Directory of Open Access Journals (Sweden)

    Lu Shan

    Full Text Available The immunoglobulin Fc region is a homodimer consisted of two sets of CH2 and CH3 domains and has been exploited to generate two-arm protein fusions with high expression yields, simplified purification processes and extended serum half-life. However, attempts to generate one-arm fusion proteins with monomeric Fc, with one set of CH2 and CH3 domains, are often plagued with challenges such as weakened binding to FcRn or partial monomer formation. Here, we demonstrate the generation of a stable IgG4 Fc monomer with a unique combination of mutations at the CH3-CH3 interface using rational design combined with in vitro evolution methodologies. In addition to size-exclusion chromatography and analytical ultracentrifugation, we used multi-angle light scattering (MALS to show that the engineered Fc monomer exhibits excellent monodispersity. Furthermore, crystal structure analysis (PDB ID: 5HVW reveals monomeric properties supported by disrupted interactions at the CH3-CH3 interface. Monomeric Fc fusions with Fab or scFv achieved FcRn binding and serum half-life comparable to wildtype IgG. These results demonstrate that this monomeric IgG4 Fc is a promising therapeutic platform to extend the serum half-life of proteins in a monovalent format.

  11. Fcγ receptor expression on splenic macrophages in adult immune thrombocytopenia

    NARCIS (Netherlands)

    Audia, S; Santegoets, K; Laarhoven, A G; Vidarsson, G; Facy, O; Ortega-Deballon, P; Samson, M; Janikashvili, N; Saas, P; Bonnotte, B; Radstake, T R

    2017-01-01

    Splenic macrophages play a key role in immune thrombocytopenia (ITP) pathogenesis by clearing opsonized platelets. Fcγ receptors (FcγR) participate in this phenomenon, but their expression on splenic macrophages and their modulation by treatment have scarcely been studied in human ITP. We aimed to

  12. Development of a nonlocal convective mixing scheme with varying upward mixing rates for use in air quality and chemical transport models.

    Science.gov (United States)

    Mihailović, Dragutin T; Alapaty, Kiran; Sakradzija, Mirjana

    2008-06-01

    Asymmetrical convective non-local scheme (CON) with varying upward mixing rates is developed for simulation of vertical turbulent mixing in the convective boundary layer in air quality and chemical transport models. The upward mixing rate form the surface layer is parameterized using the sensible heat flux and the friction and convective velocities. Upward mixing rates varying with height are scaled with an amount of turbulent kinetic energy in layer, while the downward mixing rates are derived from mass conservation. This scheme provides a less rapid mass transport out of surface layer into other layers than other asymmetrical convective mixing schemes. In this paper, we studied the performance of a nonlocal convective mixing scheme with varying upward mixing in the atmospheric boundary layer and its impact on the concentration of pollutants calculated with chemical and air-quality models. This scheme was additionally compared versus a local eddy-diffusivity scheme (KSC). Simulated concentrations of NO(2) and the nitrate wet deposition by the CON scheme are closer to the observations when compared to those obtained from using the KSC scheme. Concentrations calculated with the CON scheme are in general higher and closer to the observations than those obtained by the KSC scheme (of the order of 15-20%). Nitrate wet deposition calculated with the CON scheme are in general higher and closer to the observations than those obtained by the KSC scheme. To examine the performance of the scheme, simulated and measured concentrations of a pollutant (NO(2)) and nitrate wet deposition was compared for the year 2002. The comparison was made for the whole domain used in simulations performed by the chemical European Monitoring and Evaluation Programme Unified model (version UNI-ACID, rv2.0) where schemes were incorporated.

  13. Two-phase pressure drop and flow visualization of FC-72 in a silicon microchannel heat sink

    International Nuclear Information System (INIS)

    Megahed, Ayman; Hassan, Ibrahim

    2009-01-01

    The rapid development of two-phase microfluidic devices has triggered the demand for a detailed understanding of the flow characteristics inside microchannel heat sinks to advance the cooling process of micro-electronics. The present study focuses on the experimental investigation of pressure drop characteristics and flow visualization of a two-phase flow in a silicon microchannel heat sink. The microchannel heat sink consists of a rectangular silicon chip in which 45 rectangular microchannels were chemically etched with a depth of 276 μm, width of 225 μm, and a length of 16 mm. Experiments are carried out for mass fluxes ranging from 341 to 531 kg/m 2 s and heat fluxes from 60.4 to 130.6 kW/m 2 using FC-72 as the working fluid. Bubble growth and flow regimes are observed using high speed visualization. Three major flow regimes are identified: bubbly, slug, and annular. The frictional two-phase pressure drop increases with exit quality for a constant mass flux. An assessment of various pressure drop correlations reported in the literature is conducted for validation. A new general correlation is developed to predict the two-phase pressure drop in microchannel heat sinks for five different refrigerants. The experimental pressure drops for laminar-liquid laminar-vapor and laminar-liquid turbulent-vapor flow conditions are predicted by the new correlation with mean absolute errors of 10.4% and 14.5%, respectively.

  14. Preparation and Characterization of FC Films Coated on PET Substrates by RF Magnetron Sputtering

    Directory of Open Access Journals (Sweden)

    Huang Mei-lin

    2018-01-01

    Full Text Available Fluorocarbon (FC films were prepared on polyethylene terephthalate (PET plates and PET fabrics respectively by a radiofrequency (RF magnetron sputtering technique using polytetrafluoroethylene (PTFE as a target. Scanning electron microscope and X-ray photoelectron spectroscopy were used to investigate the morphology, structure and composition of the obtained FC films. The hydrophobicity and uvioresistant properties of the FC film coated fabric were studied. The results show that the FC films were successfully deposited on the PET substrates by a RF magnetron sputtering. The deposited films are made up of four components -CF3, -CF2-, CF- and -C-. The proportions of the four components and surface morphologies of the deposited films vary with the sputtering conditions. Compared with the original fabric samples, the hydrophobicity of the FC film coated fabrics is quite good and improved significantly.

  15. Effects of altered FcγR binding on antibody pharmacokinetics in cynomolgus monkeys

    Science.gov (United States)

    Leabman, Maya K; Meng, Y Gloria; Kelley, Robert F; DeForge, Laura E; Cowan, Kyra J; Iyer, Suhasini

    2013-01-01

    Antibody interactions with Fcγ receptors (FcγRs), like FcγRIIIA, play a critical role in mediating antibody effector functions and thereby contribute significantly to the biologic and therapeutic activity of antibodies. Over the past decade, considerable work has been directed towards production of antibodies with altered binding affinity to FcγRs and evaluation of how the alterations modulate their therapeutic activity. This has been achieved by altering glycosylation status at N297 or by engineering modifications in the crystallizable fragment (Fc) region. While the effects of these modifications on biologic activity and efficacy have been examined, few studies have been conducted to understand their effect on antibody pharmacokinetics (PK). We present here a retrospective analysis in which we characterize the PK of three antibody variants with decreased FcγR binding affinity caused by amino acid substitutions in the Fc region (N297A, N297G, and L234A/L235A) and three antibody variants with increased FcγRIIIA binding affinity caused by afucosylation at N297, and compare their PK to corresponding wild type antibody PK in cynomolgus monkeys. For all antibodies, PK was examined at a dose that was known to be in the linear range. Since production of the N297A and N297G variants in Chinese hamster ovary cells results in aglycosylated antibodies that do not bind to FcγRs, we also examined the effect of expression of an aglycosylated antibody, without sequence change(s), in E. coli. All the variants demonstrated similar PK compared with that of the wild type antibodies, suggesting that, for the six antibodies presented here, altered FcγR binding affinity does not affect PK. PMID:24492343

  16. Look Up for Healing: Embodiment of the Heal Concept in Looking Upward.

    Directory of Open Access Journals (Sweden)

    N D Leitan

    Full Text Available Conceptual processing may not be restricted to the mind. The heal concept has been metaphorically associated with an "up" bodily posture. Perceptual Symbol Systems (PSS theory suggests that this association is underpinned by bodily states which occur during learning and become instantiated as the concept. Thus the aim of this study was to examine whether processing related to the heal concept is promoted by priming the bodily state of looking upwards.We used a mixed 2x2 priming paradigm in which 58 participants were asked to evaluate words as either related to the heal concept or not after being primed to trigger the concept of looking up versus down (Direction--within subjects. A possible dose-response effect of priming was investigated via allocating participants to two 'strengths' of prime, observing an image of someone whose gaze was upward/downward (low strength and observing an image of someone whose gaze was upward/downward while physically tilting their head upwards or downwards in accord with the image (high strength (Strength--between subjects.Participants responded to words related to heal faster than words unrelated to heal across both "Strength" conditions. There was no evidence that priming was stronger in the high strength condition.The present study found that, consistent with a PSS view of cognition, the heal concept is embodied in looking upward, which has important implications for cognition, general health, health psychology, health promotion and therapy.

  17. Technique of the biomechanical analysis of execution of upward jump piked

    Directory of Open Access Journals (Sweden)

    Nataliya Batieieva

    2016-12-01

    Full Text Available Purpose: the biomechanical analysis of execution of upward jump piked. Material & Methods: the following methods of the research were used: theoretical analysis and synthesis of data of special scientific and methodical literature; photographing, video filming, biomechanical computer analysis, pedagogical observation. Students (n=8 of the chair of national choreography of the department of choreographic art of Kiev national university of culture and art took part in carrying out the biomechanical analysis of execution of upward jump piked. Results: the biomechanical analysis of execution of upward jump piked is carried out, the kinematic characteristics (way, speed, acceleration, effort of the general center of weight (GCW and center of weight (CW of biolinks of body of the executor are received (feet, shins, hips, shoulder, forearm, hands. Biokinematic models (phases are constructed. Power characteristics are defined – mechanical work and kinetic energy of links of legs and hands at execution of upward jump piked. Conclusions: it is established that the technique of execution of upward jump piked considerably influences the level of technical training of the qualified sportsmen in gymnastics (sports, in aerobic gymnastics (aerobics, diving and dancing sports.

  18. Reaction of uranium and the fluorocarbon FC-75

    Science.gov (United States)

    Young, R. H.

    1985-04-01

    Because of criticality concerns with water cooling in enriched uranium upgrading, a fluorocarbon has been evaluated as a replacement coolant for internal module components in the Plasma Separation Process (PSP). The interaction of bulk uranium and of powdered uranium with FC-75 has been investigated at temperatures between 200 and 700 C. The gas pressure and the metal temperature were monitored as a function of time. Modest temperature changes of 50 to 100 C were observed for the bulk uranium/fluorocarbon reaction. Much larger changes (up to 1000 C) were noted for the reaction involving high surface area uranium powder. These temperature transients, particularly for the powdered uranium reaction, were short-lived ( 10 seconds) and indicative of the formation of a protective layer of reaction products. Analysis of residual gas products by infrared spectroscopy indicated that one potentially serious hazard, UF6, was not present; however, several small toxic fluorocarbons were produced by thermolysis and/or reaction. X-ray diffraction analysis of the residual solids indicated UF4 and UO2 were the major solid products.

  19. Sky glint correction in measurements of upward radiance above the sea surface

    Directory of Open Access Journals (Sweden)

    Jerzy Olszewski

    2000-06-01

    Full Text Available An experiment has been performed to determine the upward water-leaving radiance by non-contact measurement of the total upward and downward radiance above the sea surface from a moving ship. The method for achieving this aim is described: the radiance meters are both tilted in such a way that the upward radiance meter can 'see' that part of the measured downward radiance which would be reflected if the water surface were smooth and which is not derived directly from solar glitter. Both meters are firmly fixed in a special frame, which ensures that the required orientation is the most probable one. Time records of the measured parameters are analysed. The results are presented in several forms: frequency (histogram analysis appears to be the most promising one.

  20. Upward lightning attachment analysis on wind turbines and correlated current parameters

    DEFF Research Database (Denmark)

    Vogel, Stephan; Ishii, M.; Saito, M.

    2017-01-01

    This work provides insight in the attachment characteristics of upward initiated lightning discharges to wind turbines and their possible consequences for the lightning protection of wind turbine blades. All discharges were recorded at the Japanese coast of the Sea of Japan which is known...... for intense upward lightning activity. 172 video recordings of lightning discharges on rotating wind turbines are analysed and attachment angle, detachment angle, and the resulting angular displacement were determined. A classification between self-initiated and other-triggered upward lightning events...... is performed by means of video analysis. The results reveal that the majority of discharges are initiated on vertical blades; however, also attachments to horizontal blades are reported. Horizontal attachment (or a slightly inclined blade state) is often related with a triggered lightning event prior...

  1. New data on two-phase water-air hydrodynamics in vertical upward and downward tubes

    Energy Technology Data Exchange (ETDEWEB)

    Lau, V [Atomic Energy of Canada Ltd., Saskatoon, SK (Canada); Rezkallah, K S [Saskatchewan Univ., Saskatoon (Canada). Mechanical Engineering Dept.

    1996-12-31

    The three key parameters involved in the analysis of the hydrodynamic characteristics of a two-phase system (i.e. pressure drop, void fraction, and flow pattern associated with the flow) are taken in vertical upward and downward tubes, using water-air mixture at atmospheric pressure. The acquired data set covers a wide range of liquid and gas flow rates, as well as void fractions. Using the acquired data set, two sets of flow pattern maps, for both upward and downward flows, are developed in the present study. Furthermore, a set of correlations for predicting the frictional pressure drop in both upward and downward flow were also developed. (author). 16 refs., 13 figs.

  2. Statistical partitioning of a three-year time series of direct urban net CO2 flux measurements into biogenic and anthropogenic components

    Science.gov (United States)

    Menzer, Olaf; McFadden, Joseph P.

    2017-12-01

    Eddy covariance flux measurements are increasingly used to quantify the net carbon dioxide exchange (FC) in urban areas. FC represents the sum of anthropogenic emissions, biogenic carbon release from plant and soil respiration, and carbon uptake by plant photosynthesis. When FC is measured in natural ecosystems, partitioning into respiration and photosynthesis is a well-established procedure. In contrast, few studies have partitioned FC at urban flux tower sites due to the difficulty of accounting for the temporal and spatial variability of the multiple sources and sinks. Here, we partitioned a three-year time series of flux measurements from a suburban neighborhood of Minneapolis-Saint Paul, Minnesota, USA. We segregated FC into one subset that captured fluxes from a residential neighborhood and into another subset that covered a golf course. For both land use types we modeled anthropogenic flux components based on winter data and extrapolated them to the growing season, to estimate gross primary production (GPP) and ecosystem respiration (Reco) at half-hourly, daily, monthly and annual scales. During the growing season, GPP had the largest magnitude (up to - 9.83 g C m-2 d-1) of any component CO2 flux, biogenic or anthropogenic, and both GPP and Reco were more dynamic seasonally than anthropogenic fluxes. Owing to the balancing of Reco against GPP, and the limitations of the growing season in a cold temperate climate zone, the net biogenic flux was only 1.5%-4.5% of the anthropogenic flux in the dominant residential land use type, and between 25%-31% of the anthropogenic flux in highly managed greenspace. Still, the vegetation sink at our site was stronger than net anthropogenic emissions on 16-20 days over the residential area and on 66-91 days over the recreational area. The reported carbon flux sums and dynamics are a critical step toward developing models of urban CO2 fluxes within and across cities that differ in vegetation cover.

  3. Configuration of gun-generated spheromak in effectively closed metal flux conserver

    International Nuclear Information System (INIS)

    Kato, Yushi; Nishikawa, Masahiro; Honda, Yoshihide; Satomi, Norio; Watanabe, Kenji

    1988-01-01

    In the CTCC-II spheromak experiment, the gun-generated plasma is confined in a spheroidal aluminum flux conserver (FC) with a choking coil. This coil produces the additional magnetic field to close perfectly all magnetic surfaces into the FC, i.e. the entrance hole for plasma injection is enable to be closed by magnetic field. Hence the plasma is confined in the effectively closed metal FC. In this experiment the average life time is 1.2 msec, and electron density and temperature are n e = 2 x 10 13 /cc, T e = 30 eV, respectively. The configuration with a flux hole region in which the toroidal magnetic field vanishes around the geometrical axis has been observed in the FC. The radius of the flux hole depends on the condition how the external choking field is applied. The flux hole enhances the magnetic shear near the plasma surfaces and, therefore, has a stabilizing effect even without inserting the central conducting pole. (author)

  4. Modulating Cytotoxic Effector Functions by Fc Engineering to Improve Cancer Therapy.

    Science.gov (United States)

    Kellner, Christian; Otte, Anna; Cappuzzello, Elisa; Klausz, Katja; Peipp, Matthias

    2017-09-01

    In the last two decades, monoclonal antibodies have revolutionized the therapy of cancer patients. Although antibody therapy has continuously been improved, still a significant number of patients do not benefit from antibody therapy. Therefore, rational optimization of the antibody molecule by Fc engineering represents a major area of translational research to further improve this potent therapeutic option. Monoclonal antibodies are able to trigger a variety of effector mechanisms. Especially Fc-mediated effector functions such as antibody-dependent cell-mediated cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP), and complement- dependent cytotoxicity (CDC) are considered important in antibody therapy of cancer. Novel mechanistic insights into the action of monoclonal antibodies allowed the development of various Fc engineering approaches to modulate antibodies' effector functions. Strategies in modifying the Fc glycosylation profile (Fc glyco-engineering) or approaches in engineering the protein backbone (Fc protein engineering) have been intensively evaluated. In the current review, Fc engineering strategies resulting in improved ADCC, ADCP and CDC activity are summarized and discussed.

  5. Anti-influenza Hyperimmune Immunoglobulin Enhances Fc-functional Antibody Immunity during Human Influenza Infection.

    Science.gov (United States)

    Vanderven, Hillary A; Wragg, Kathleen; Ana-Sosa-Batiz, Fernanda; Kristensen, Anne B; Jegaskanda, Sinthujan; Wheatley, Adam K; Wentworth, Deborah; Wines, Bruce D; Hogarth, P Mark; Rockman, Steve; Kent, Stephen J

    2018-05-31

    New treatments for severe influenza are needed. Passive transfer of influenza-specific hyperimmune pooled immunoglobulin (Flu-IVIG) boosts neutralising antibody responses to past strains in influenza-infected subjects. The effect of Flu-IVIG on antibodies with Fc-mediated functions, which may target diverse influenza strains, is unclear. We studied the capacity of Flu-IVIG, relative to standard IVIG, to bind to Fc receptors and mediate antibody-dependent cellular cytotoxicity in vitro. The effect of Flu-IVIG infusion, compared to placebo infusion, was examined in serial plasma samples from 24 subjects with confirmed influenza infection in the INSIGHT FLU005 pilot study. Flu-IVIG contains higher concentrations of Fc-functional antibodies than IVIG against a diverse range of influenza hemagglutinins. Following infusion of Flu-IVIG into influenza-infected subjects, a transient increase in Fc-functional antibodies was present for 1-3 days against infecting and non-infecting strains of influenza. Flu-IVIG contains antibodies with Fc-mediated functions against influenza virus and passive transfer of Flu-IVIG increases anti-influenza Fc-functional antibodies in the plasma of influenza-infected subjects. Enhancement of Fc-functional antibodies to a diverse range of influenza strains suggests that Flu-IVIG infusion could prove useful in the context of novel influenza virus infections, when there may be minimal or no neutralising antibodies in the Flu-IVIG preparation.

  6. Increase in neutrophil Fc gamma receptor I expression following interferon gamma treatment in rheumatoid arthritis.

    Science.gov (United States)

    Goulding, N J; Knight, S M; Godolphin, J L; Guyre, P M

    1992-04-01

    The therapeutic potential of interferon gamma (IFN gamma) in a number of disease states is still being explored, but progress is hampered by the lack of a suitable measure of in vivo biological activity. To assess the in vivo biological effects of recombinant human IFN gamma (rhIFN gamma), 14 patients were studied in a randomised, prospective, double blind, placebo controlled trial of this cytokine for the treatment of rheumatoid arthritis. The levels of Fc gamma receptors on peripheral blood neutrophils were measured at baseline and after 21 days of once daily, subcutaneous injections of rhIFN gamma or placebo. An induction of neutrophil Fc gamma receptor type I (Fc gamma RI) was seen in the group of patients receiving recombinant human rhIFN gamma but not in those receiving placebo. No change in the expression of Fc gamma RII or Fc gamma RIII was detected. The amount of induction of Fc gamma RI detected on the neutrophils of patients receiving rhIFN gamma did not correlate with clinical measures of response at either 21 days or at the end of the study (24 weeks). No significant clinical responses were observed in the rhIFN gamma group at these times. These data confirm that the reported in vitro effect of IFN gamma on human neutrophil Fc receptor expression can be reproduced in vivo.

  7. Matter effects in upward-going muons and sterile neutrino oscillations

    CERN Document Server

    Ambrosio, M; Auriemma, G; Bakari, D; Baldini, A; Barbarino, G C; Barish, B C; Battistoni, G; Becherini, Y; Bellotti, R; Bemporad, C; Bernardini, P; Bilokon, H; Bisi, V; Bloise, C; Bower, C; Brigida, M; Bussino, S; Cafagna, F; Calicchio, M; Campana, D; Carboni, M; Caruso, R; Cecchini, S; Cei, F; Chiarella, V; Choudhary, B C; Coutu, S; De Cataldo, G; Dekhissi, H; De Marzo, C; De Mitri, I; Derkaoui, J E; De Vincenzi, M; Di Credico, A; Erriquez, O; Favuzzi, C; Forti, C; Fusco, P; Giacomelli, G; Giannini, G; Giglietto, N; Giorgini, M; Grassi, M; Gray, L; Grillo, A; Guarino, F; Gustavino, C; Habig, A; Hanson, K; Heinz, R; Iarocci, Enzo; Katsavounidis, E; Katsavounidis, I; Kearns, E T; Kim, H; Kyriazopoulou, S; Lammanna, E; Lane, C; Levins, D S; Lipari, P; Longley, N P; Longo, M J; Loparco, F; Maaroufi, F; Mancarella, G; Mandrioli, G; Margiotta, A; Marini, A; Martello, D; Marzari-Chiesa, A; Mazziotta, M N; Michael, D G; Mikheyev, S P; Miller, L; Monacelli, P; Montaruli, T; Monteno, M; Mufson, S L; Musser, J; Nicolò, D; Nolty, R; Orth, C; Osteria, G; Palamara, O; Patera, V; Patrizii, L; Pazzi, R; Peck, C W; Perrone, L; Petrera, S; Pistilli, P; Popa, V; Rainó, A; Reynoldson, J; Ronga, F; Rrhioua, A; Satriano, C; Scapparone, E; Scholberg, K; Sciubba, A; Serra, P; Sioli, M; Sirri, G; Sitta, M; Spinelli, P; Spinetti, M; Spurio, M; Steinberg, R; Stone, J L; Sulak, Lawrence R; Surdo, A; Tarle, G; Togo, V; Vakili, M; Walter, C W; Webb, R

    2001-01-01

    The angular distribution of upward-going muons produced by atmospheric neutrinos in the rock below the MACRO detector shows anomalies in good agreement with two flavor nu /sub mu / to nu /sub tau / oscillations with maximum mixing and Delta m/sup 2/ around 0.0024 eV/sup 2/. Exploiting the dependence of magnitude of the matter effect on the oscillation channel, and using a set of 809 upward-going muons observed in MACRO, we show that the two flavor nu /sub mu / to nu /sub s/ oscillation is disfavored with 99% C.L. with respect to nu /sub mu / to nu /sub tau /. (29 refs).

  8. Neutron Reflection Study of Surface Adsorption of Fc, Fab, and the Whole mAb.

    Science.gov (United States)

    Li, Zongyi; Li, Ruiheng; Smith, Charles; Pan, Fang; Campana, Mario; Webster, John R P; van der Walle, Christopher F; Uddin, Shahid; Bishop, Steve M; Narwal, Rojaramani; Warwicker, Jim; Lu, Jian Ren

    2017-07-12

    Characterizing the influence of fragment crystallization (Fc) and antigen-binding fragment (Fab) on monoclonal antibody (mAb) adsorption at the air/water interface is an important step to understanding liquid mAb drug product stability during manufacture, shipping, and storage. Here, neutron reflection is used to study the air/water adsorption of a mAb and its Fc and Fab fragments. By varying the isotopic contrast, the adsorbed amount, thickness, orientation, and immersion of the adsorbed layers could be determined unambiguously. While Fc adsorption reached saturation within the hour, its surface adsorbed amount showed little variation with bulk concentration. In contrast, Fab adsorption was slower and the adsorbed amount was concentration dependent. The much higher Fc adsorption, as compared to Fab, was linked to its lower surface charge. Time and concentration dependence of mAb adsorption was dominated by Fab behavior, although both Fab and Fc behaviors contributed to the amount of mAb adsorbed. Changing the pH from 5.5 to 8.8 did not much perturb the adsorbed amount of Fc, Fab, or mAb. However, a small decrease in adsorption was observed for the Fc over pH 8-8.8 and vice versa for the Fab and mAb, consistent with a dominant Fab behavior. As bulk concentration increased from 5 to 50 ppm, the thicknesses of the Fc layers were almost constant at 40 Å, while Fab and mAb layers increased from 45 to 50 Å. These results imply that the adsorbed mAb, Fc, and Fab all retained their globular structures and were oriented with their short axial lengths perpendicular to the interface.

  9. A novel activating chicken IgY FcR is related to leukocyte receptor complex (LRC)

    NARCIS (Netherlands)

    Viertlboeck, B.C.; Schmitt, R.; Hanczaruk, M.A.; Crooijmans, R.P.M.A.; Groenen, M.A.M.; Gobel, T.W.

    2009-01-01

    FcRs have multifaceted roles in the immune system. Chicken FcRs were demonstrated on macrophages decades ago; however, only recently the chicken Ig-like receptor AB1, encoded in the leukocyte receptor complex, was molecularly identified as a high-affinity FcR. The present study was initiated to

  10. Chicken IgY Fc expressed by Eimeria mitis enhances the immunogenicity of E. mitis.

    Science.gov (United States)

    Qin, Mei; Tang, Xinming; Yin, Guangwen; Liu, Xianyong; Suo, Jingxia; Tao, Geru; Ei-Ashram, Saeed; Li, Yuan; Suo, Xun

    2016-03-21

    Eimeria species are obligate intracellular apicomplexan parasites, causing great economic losses in the poultry industry. Currently wild-and attenuated- type anticoccidial vaccines are used to control coccidiosis. However, their use in fast growing broilers is limited by vaccination side effects caused by medium and/or low immunogenic Eimeria spp. There is, therefore, a need for a vaccine with high immunogenicity for broilers. The avian yolk sac IgY Fc is the avian counterpart of the mammalian IgG Fc, which enhances immunogenicity of Fc-fusion proteins. Here, we developed a stable transgenic Eimeria mitis expressing IgY Fc (Emi.chFc) and investigated whether the avian IgY Fc fragment enhances the immunogenicity of E. mitis. Two-week-old broilers were immunized with either Emi.chFc or wild type Eimeria and challenged with wild type E. mitis to analyze the protective properties of transgenic Emi.chFc. Chickens immunized with Emi.chFc had significantly lower oocyst output, in comparison with PBS, mock control (transgenic E. mitis expressing HA1 from H9N2 avian influenza virus) and wildtype E. mitis immunized groups after challenge, indicating that IgY Fc enhanced the immunogenicity of E. mitis. Our findings suggest that IgY Fc-expressing Eimeria may be a better coccidiosis vaccine, and transgenic Eimeria expressing Fc-fused exogenous antigens may be used as a novel vaccine-delivery vehicle against a wide variety of pathogens.

  11. Natural form of noncytolytic flexible human Fc as a long-acting carrier of agonistic ligand, erythropoietin.

    Directory of Open Access Journals (Sweden)

    Se Jin Im

    Full Text Available Human IgG1 Fc has been widely used as a bioconjugate, but exhibits shortcomings, such as antibody- and complement-mediated cytotoxicity as well as decreased bioactivity, when applied to agonistic proteins. Here, we constructed a nonimmunogenic, noncytolytic and flexible hybrid Fc (hyFc consisting of IgD and IgG4, and tested its function using erythropoietin (EPO conjugate, EPO-hyFc. Despite low amino acid homology (20.5% between IgD Fc and IgG4 Fc, EPO-hyFc retained "Y-shaped" structure and repeated intravenous administrations of EPO-hyFc into monkeys did not generate EPO-hyFc-specific antibody responses. Furthermore, EPO-hyFc could not bind to FcγR I and C1q in contrast to EPO-IgG1 Fc. In addition, EPO-hyFc exhibited better in vitro bioactivity and in vivo bioactivity in rats than EPO-IgG1 Fc, presumably due to the high flexibility of IgD. Moreover, the mean serum half-life of EPO-hyFc(H, a high sialic acid content form of EPO-hyFc, was approximately 2-fold longer than that of the heavily glycosylated EPO, darbepoetin alfa, in rats. More importantly, subcutaneous injection of EPO-hyFc(H not only induced a significantly greater elevation of serum hemoglobin levels than darbepoetin alfa in both normal rats and cisplatin-induced anemic rats, but also displayed a delayed time to maximal serum level and twice final area-under-the-curve (AUC(last. Taken together, hyFc might be a more attractive Fc conjugate for agonistic proteins/peptides than IgG1 Fc due to its capability to elongate their half-lives without inducing host effector functions and hindering bioactivity of fused molecules. Additionally, a head-to-head comparison demonstrated that hyFc-fusion strategy more effectively improved the in vivo bioactivity of EPO than the hyperglycosylation approach.

  12. Natural form of noncytolytic flexible human Fc as a long-acting carrier of agonistic ligand, erythropoietin.

    Science.gov (United States)

    Im, Se Jin; Yang, Sang In; Yang, Se Hwan; Choi, Dong Hoon; Choi, So Young; Kim, Hea Sook; Jang, Do Soo; Jin, Kyeong Sik; Chung, Yo-Kyung; Kim, Seung-Hee; Paik, Sang Hoon; Park, Yoo Chang; Chung, Moon Koo; Kim, Yong Bum; Han, Kang-Hyun; Choi, Kwan Yong; Sung, Young Chul

    2011-01-01

    Human IgG1 Fc has been widely used as a bioconjugate, but exhibits shortcomings, such as antibody- and complement-mediated cytotoxicity as well as decreased bioactivity, when applied to agonistic proteins. Here, we constructed a nonimmunogenic, noncytolytic and flexible hybrid Fc (hyFc) consisting of IgD and IgG4, and tested its function using erythropoietin (EPO) conjugate, EPO-hyFc. Despite low amino acid homology (20.5%) between IgD Fc and IgG4 Fc, EPO-hyFc retained "Y-shaped" structure and repeated intravenous administrations of EPO-hyFc into monkeys did not generate EPO-hyFc-specific antibody responses. Furthermore, EPO-hyFc could not bind to FcγR I and C1q in contrast to EPO-IgG1 Fc. In addition, EPO-hyFc exhibited better in vitro bioactivity and in vivo bioactivity in rats than EPO-IgG1 Fc, presumably due to the high flexibility of IgD. Moreover, the mean serum half-life of EPO-hyFc(H), a high sialic acid content form of EPO-hyFc, was approximately 2-fold longer than that of the heavily glycosylated EPO, darbepoetin alfa, in rats. More importantly, subcutaneous injection of EPO-hyFc(H) not only induced a significantly greater elevation of serum hemoglobin levels than darbepoetin alfa in both normal rats and cisplatin-induced anemic rats, but also displayed a delayed time to maximal serum level and twice final area-under-the-curve (AUC(last)). Taken together, hyFc might be a more attractive Fc conjugate for agonistic proteins/peptides than IgG1 Fc due to its capability to elongate their half-lives without inducing host effector functions and hindering bioactivity of fused molecules. Additionally, a head-to-head comparison demonstrated that hyFc-fusion strategy more effectively improved the in vivo bioactivity of EPO than the hyperglycosylation approach.

  13. Critical flux determination by flux-stepping

    DEFF Research Database (Denmark)

    Beier, Søren; Jonsson, Gunnar Eigil

    2010-01-01

    In membrane filtration related scientific literature, often step-by-step determined critical fluxes are reported. Using a dynamic microfiltration device, it is shown that critical fluxes determined from two different flux-stepping methods are dependent upon operational parameters such as step...... length, step height, and.flux start level. Filtrating 8 kg/m(3) yeast cell suspensions by a vibrating 0.45 x 10(-6) m pore size microfiltration hollow fiber module, critical fluxes from 5.6 x 10(-6) to 1.2 x 10(-5) m/s have been measured using various step lengths from 300 to 1200 seconds. Thus......, such values are more or less useless in itself as critical flux predictors, and constant flux verification experiments have to be conducted to check if the determined critical fluxes call predict sustainable flux regimes. However, it is shown that using the step-by-step predicted critical fluxes as start...

  14. Effect of trastuzumab interchain disulfide bond cleavage on Fcγ receptor binding and antibody-dependent tumour cell phagocytosis.

    Science.gov (United States)

    Suzuki, Mami; Yamanoi, Ayaka; Machino, Yusuke; Ootsubo, Michiko; Izawa, Ken-ichi; Kohroki, Junya; Masuho, Yasuhiko

    2016-01-01

    The Fc domain of human IgG1 binds to Fcγ receptors (FcγRs) to induce effector functions such as phagocytosis. There are four interchain disulfide bonds between the H and L chains. In this study, the disulfide bonds within the IgG1 trastuzumab (TRA), which is specific for HER2, were cleaved by mild S-sulfonation or by mild reduction followed by S-alkylation with three different reagents. The cleavage did not change the binding activities of TRA to HER2-bearing SK-BR-3 cells. The binding activities of TRA to FcγRIIA and FcγRIIB were greatly enhanced by modification with mild reduction and S-alkylation with ICH2CONH2 or N-(4-aminophenyl) maleimide, while the binding activities of TRA to FcγRI and FcγRIIIA were decreased by any of the four modifications. However, the interchain disulfide bond cleavage by the different modifications did not change the antibody-dependent cell-mediated phagocytosis (ADCP) of SK-BR-3 cells by activated THP-1 cells. The order of FcγR expression levels on the THP-1 cells was FcγRII > FcγRI > FcγRIII and ADCP was inhibited by blocking antibodies against FcγRI and FcγRII. These results imply that the effect of the interchain disulfide bond cleavage on FcγRs binding and ADCP is dependent on modifications of the cysteine residues and the FcγR isotypes. © The Authors 2015. Published by Oxford University Press on behalf of the Japanese Biochemical Society. All rights reserved.

  15. Comprehensive evaluation of cesium removal by CuFC adsorption. The effects of initial concentration, CuFC dosage and co-existing ions in solution

    International Nuclear Information System (INIS)

    Yao Xu; Ping Gu; Guang-Hui Zhang; Jun Zhao; Lu Wang; Xiang-Zhu Xiao; Fei Han

    2017-01-01

    To use copper ferrocyanide (CuFC) more efficiently in wastewater treatment, the method of isotope carrying used in "1"3"7Cs removal was investigated. A calculation model based on Freundlich isotherm was established to determine the optimum initial cesium concentration, at which the highest decontamination factor (DF) could be obtained at a certain CuFC dosage. An accurate DF prediction model was developed to describe synergistic effects of sodium and potassium. A novel index called volumetric distribution coefficient (K_v_d) was proposed to evaluate adsorption performance in terms of DF and concentration factor. (author)

  16. On the Upward Bias of the Dissimilarity Index and Its Corrections

    Science.gov (United States)

    Mazza, Angelo; Punzo, Antonio

    2015-01-01

    The dissimilarity index of Duncan and Duncan is widely used in a broad range of contexts to assess the overall extent of segregation in the allocation of two groups in two or more units. Its sensitivity to random allocation implies an upward bias with respect to the unknown amount of systematic segregation. In this article, following a multinomial…

  17. Upward Feedback and Its Contribution to Employees' Feeling of Self-Determination

    Science.gov (United States)

    Bauer, Johannes; Mulder, Regina H.

    2006-01-01

    Purpose--The paper seeks to show that self-determination is a widely regarded motivational variable in educational research that relates to intrinsically motivated, self-directed learning at work. This study aimed to find out whether the possibility to provide upward feedback to supervisors contributes to employees' feelings of self-determination.…

  18. Summer Upward Bound, Terre Haute, Indiana. Secondary Program in Compensatory Education, 4.

    Science.gov (United States)

    American Institutes for Research in the Behavioral Sciences, Palo Alto, CA.

    Upward Bound was a precollege program geared for high school students with potential who had been handicapped by economic, cultural, and educational deprivation. It involved a full-time summer program and follow-up programs (counseling, cultural activities, and physical education) during the academic year. Students stayed in the program for three…

  19. 77 FR 37016 - Applications for New Awards: Upward Bound Math and Science Program

    Science.gov (United States)

    2012-06-20

    ... DEPARTMENT OF EDUCATION Applications for New Awards: Upward Bound Math and Science Program AGENCY... Bound Math and Science Program. Notice inviting applications for new awards for fiscal year (FY) 2012.... There are three types of grants under the UB Program: regular UB grants, Veterans UB grants, and UB Math...

  20. Species interactions slow warming-induced upward shifts of treelines on the Tibetan Plateau.

    Science.gov (United States)

    Liang, Eryuan; Wang, Yafeng; Piao, Shilong; Lu, Xiaoming; Camarero, Jesús Julio; Zhu, Haifeng; Zhu, Liping; Ellison, Aaron M; Ciais, Philippe; Peñuelas, Josep

    2016-04-19

    The alpine treeline is commonly regarded as being sensitive to climatic warming because regeneration and growth of trees at treeline generally are limited by low temperature. The alpine treelines of the Tibetan Plateau (TP) occur at the highest elevations (4,900 m above sea level) in the Northern Hemisphere. Ongoing climatic warming is expected to shift treelines upward. Studies of treeline dynamics at regional and local scales, however, have yielded conflicting results, indicating either unchanging treeline elevations or upward shifts. To reconcile this conflict, we reconstructed in detail a century of treeline structure and tree recruitment at sites along a climatic gradient of 4 °C and mean annual rainfall of 650 mm on the eastern TP. Species interactions interacted with effects of warming on treeline and could outweigh them. Densification of shrubs just above treeline inhibited tree establishment, and slowed upward movement of treelines on a time scale of decades. Interspecific interactions are major processes controlling treeline dynamics that may account for the absence of an upward shift at some TP treelines despite continued climatic warming.

  1. UPWARD POWER TENDENCIES IN A HIERARCHY - POWER DISTANCE THEORY VERSUS BUREAUCRATIC RULE

    NARCIS (Netherlands)

    WILKE, HAM

    1993-01-01

    Two contrasting notions concerning upward power tendencies within hierarchically structured groups are investigated. Power Distance Theory assumes that people have a desire for power that results in a tendency to reduce the power distance towards a more powerful other, and this tendency is assumed

  2. Upward Appraisal: A Tool for the Continuous Improvement of Library Managers' Skills.

    Science.gov (United States)

    Stein, Joan E.

    Effective management and the importance of feedback in relation to improvement are becoming critical issues for libraries. Upward appraisal evaluates managers' performance based on input from their staff, rather than the traditional top-down evaluation format in which a manager is evaluated solely by their superior. This paper discusses the…

  3. AIMING AT THE TOP - UPWARD SOCIAL-COMPARISON OF ABILITIES AFTER FAILURE

    NARCIS (Netherlands)

    YBEMA, JF; BUUNK, BP

    1993-01-01

    This study examined the effects of feedback on a task on information seeking and partner preferences as forms of social comparison. It was predicted that subjects who experienced failure and perceived control over future performance would, for reasons of self-improvement, choose more strongly upward

  4. Species interactions slow warming-induced upward shifts of treelines on the Tibetan Plateau

    Science.gov (United States)

    Liang, Eryuan; Wang, Yafeng; Piao, Shilong; Lu, Xiaoming; Camarero, Jesús Julio; Zhu, Haifeng; Zhu, Liping; Ciais, Philippe; Peñuelas, Josep

    2016-01-01

    The alpine treeline is commonly regarded as being sensitive to climatic warming because regeneration and growth of trees at treeline generally are limited by low temperature. The alpine treelines of the Tibetan Plateau (TP) occur at the highest elevations (4,900 m above sea level) in the Northern Hemisphere. Ongoing climatic warming is expected to shift treelines upward. Studies of treeline dynamics at regional and local scales, however, have yielded conflicting results, indicating either unchanging treeline elevations or upward shifts. To reconcile this conflict, we reconstructed in detail a century of treeline structure and tree recruitment at sites along a climatic gradient of 4 °C and mean annual rainfall of 650 mm on the eastern TP. Species interactions interacted with effects of warming on treeline and could outweigh them. Densification of shrubs just above treeline inhibited tree establishment, and slowed upward movement of treelines on a time scale of decades. Interspecific interactions are major processes controlling treeline dynamics that may account for the absence of an upward shift at some TP treelines despite continued climatic warming. PMID:27044083

  5. Doing worse, but feeling happy : Social comparison and identification in response to upward and downward targets

    NARCIS (Netherlands)

    Groothof, H.; Siero, F.W.; Buunk, Abraham (Bram)

    2007-01-01

    We investigated people's responses to exposure to downward and upward targets. In Study 1, among 197 participants, it was predicted and found that such exposure led to a contrast effect on self-evaluation, and to an assimilation effect on affect. In Study 2, among 148 participants, it was predicted

  6. Lifting the Veil: A Realist Critique of Sistema's Upwardly Mobile Path

    Science.gov (United States)

    Logan, Owen

    2016-01-01

    El Sistema sits somewhere between a social project and a classical music initiative. However, its promise of delivering upward mobility has not been sufficiently examined as a structural phenomenon which dovetails with critical policy issues in taxation, educational provision, human rights, and welfare. This article argues that Sistema-style…

  7. Upwardly Mobile: Attitudes toward the Class Transition among First-Generation College Students

    Science.gov (United States)

    Hinz, Serena E.

    2016-01-01

    First-generation, working-class college students are on the path to upward mobility and may have social and psychological problems related to cultural differences between the working class and the middle class. In her study, Hurst (2007, 2010) reports that students of working-class origin often choose loyalty to one class. However, I revise…

  8. Feeling bad, but satisfied : the effects of upward and downward comparison upon mood and marital satisfaction

    NARCIS (Netherlands)

    Buunk, B.P.; Ybema, J.F.

    2003-01-01

    In a sample of 135 women from rural areas, the effects of social comparison with the marriage of another woman upon mood, identification and relationship evaluation were examined. Upward targets evoked a more positive mood, and a less negative mood than downward targets, while, in contrast, the

  9. Physical mechanism and numerical simulation of the inception of the lightning upward leader

    International Nuclear Information System (INIS)

    Li Qingmin; Lu Xinchang; Shi Wei; Zhang Li; Zou Liang; Lou Jie

    2012-01-01

    The upward leader is a key physical process of the leader progression model of lightning shielding. The inception mechanism and criterion of the upward leader need further understanding and clarification. Based on leader discharge theory, this paper proposes the critical electric field intensity of the stable upward leader (CEFISUL) and characterizes it by the valve electric field intensity on the conductor surface, E L , which is the basis of a new inception criterion for the upward leader. Through numerical simulation under various physical conditions, we verified that E L is mainly related to the conductor radius, and data fitting yields the mathematical expression of E L . We further establish a computational model for lightning shielding performance of the transmission lines based on the proposed CEFISUL criterion, which reproduces the shielding failure rate of typical UHV transmission lines. The model-based calculation results agree well with the statistical data from on-site operations, which show the effectiveness and validity of the CEFISUL criterion.

  10. A Diary Study of Self-Compassion, Upward Social Comparisons, and Body Image-Related Outcomes.

    Science.gov (United States)

    Thøgersen-Ntoumani, Cecilie; Dodos, Louisa; Chatzisarantis, Nikos; Ntoumanis, Nikos

    2017-07-01

    Self-compassion may protect individuals experiencing poor body image and associated maladaptive outcomes. The purpose of the study was to examine within-person associations (whilst controlling for between-person differences) between appearance-related self-compassion, appearance-related threats (operationalised as upward appearance comparisons), and body image-related variables, namely, social physique anxiety, drive for thinness, and body dissatisfaction. A diary methodology was used whereby young women (n = 126; M age = 21.26) responded to brief online surveys three times per day (11am, 3pm, and 7pm) every second day for one week (i.e. a total of 12 measurement points). Results of mixed linear modeling revealed that both state appearance-related upward comparisons and self-compassion independently predicted all three outcomes in a positive and negative fashion, respectively. No significant interaction effects between state appearance-related upward comparisons and self-compassion were found. The results suggested that appearance-based self-compassion was important, not just when there was a potential threat to body image via upward appearance comparisons. The findings highlight the importance of fostering self-compassion on a daily level. © 2017 The International Association of Applied Psychology.

  11. Upward migration of radio-cesium and strontium in a sand-filled lysimeter

    International Nuclear Information System (INIS)

    Sanford, W.E.; Larsen, I.L.; McConnell, J.W.; Rogers, R.D.

    1998-01-01

    The upward migration of 134 Cs, 137 Cs, and 90 Sr was observed in a silica sand-filled lysimeter at the Field Lysimeter Investigations: Low Level Waste Data Base Development experiment site at Oak Ridge National Laboratory. The source of the radionuclides first observed on the surface was identified from isotopic analysis as being from the buried waste. Cores of the sand were collected and analyzed for the vertical distribution of the radionuclides. Results of analyses revealed that pulses (elevated levels) in the activity of the Cs and Sr radioisotopes occurred at the same depths. During the sectioning of the sand core collected from directly above the buried waste form it was discovered that a fine root from an unidentified plant was present throughout all but the upper few centimeters of the core. Because the upward migration was unexpected, information that may lead to the determination of a definitive mechanism of migration was not preserved. The distribution of the radionuclides coupled with the presence of the root suggest that Cs and Sr migrated upward in the evapotranspiration stream of the root. Further study must be undertaken to confirm this phenomenon. Upward migration of radionuclides as observed here could result in direct exposures and offsite releases from underground storage facilities. (Copyright (c) 1998 Elsevier Science B.V., Amsterdam. All rights reserved.)

  12. Reward acts on the pFC to enhance distractor resistance of working memory representations.

    Science.gov (United States)

    Fallon, Sean James; Cools, Roshan

    2014-12-01

    Working memory and reward processing are often thought to be separate, unrelated processes. However, most daily activities involve integrating these two types of information, and the two processes rarely, if ever, occur in isolation. Here, we show that working memory and reward interact in a task-dependent manner and that this task-dependent interaction involves modulation of the pFC by the ventral striatum. Specifically, BOLD signal during gains relative to losses in the ventral striatum and pFC was associated not only with enhanced distractor resistance but also with impairment in the ability to update working memory representations. Furthermore, the effect of reward on working memory was accompanied by differential coupling between the ventral striatum and ignore-related regions in the pFC. Together, these data demonstrate that reward-related signals modulate the balance between cognitive stability and cognitive flexibility by altering functional coupling between the ventral striatum and the pFC.

  13. High Efficiency Advanced Lightweight Fuel Cell (HEAL-FC), Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — Infinity's High Efficiency Advanced Lightweight Fuel Cell (HEAL FC) is an improved version of its current fuel cell technology developed for space applications. The...

  14. Operations and Maintenance Manual for Expanded Bioventing System Site FC-2 Kelly AFB, Texas

    National Research Council Canada - National Science Library

    1996-01-01

    This Operations and Maintenance Manual has been created as a guide for monitoring and maintaining the performance of the bioventing blower and vent well plumbing at the Fire Training Area (Site FC-2...

  15. FC-TLBO: fully constrained meta-heuristic algorithm for abundance ...

    Indian Academy of Sciences (India)

    Omprakash Tembhurne

    hyperspectral unmixing; meta-heuristic approach; teaching-learning-based optimisation (TLBO). 1. ... area of research due to its real-time applications. Satellite .... describes the detailed methodology of proposed FC-TLBO. Section 4 contains ...

  16. An Extreme-ultraviolet Wave Generating Upward Secondary Waves in a Streamer-like Solar Structure

    Science.gov (United States)

    Zheng, Ruisheng; Chen, Yao; Feng, Shiwei; Wang, Bing; Song, Hongqiang

    2018-05-01

    Extreme-ultraviolet (EUV) waves, spectacular horizontally propagating disturbances in the low solar corona, always trigger horizontal secondary waves (SWs) when they encounter the ambient coronal structure. We present the first example of upward SWs in a streamer-like structure after the passing of an EUV wave. This event occurred on 2017 June 1. The EUV wave happened during a typical solar eruption including a filament eruption, a coronal mass ejection (CME), and a C6.6 flare. The EUV wave was associated with quasi-periodic fast propagating (QFP) wave trains and a type II radio burst that represented the existence of a coronal shock. The EUV wave had a fast initial velocity of ∼1000 km s‑1, comparable to high speeds of the shock and the QFP wave trains. Intriguingly, upward SWs rose slowly (∼80 km s‑1) in the streamer-like structure after the sweeping of the EUV wave. The upward SWs seemed to originate from limb brightenings that were caused by the EUV wave. All of the results show that the EUV wave is a fast-mode magnetohydrodynamic (MHD) shock wave, likely triggered by the flare impulses. We suggest that part of the EUV wave was probably trapped in the closed magnetic fields of the streamer-like structure, and upward SWs possibly resulted from the release of slow-mode trapped waves. It is believed that the interplay of the strong compression of the coronal shock and the configuration of the streamer-like structure is crucial for the formation of upward SWs.

  17. HIV-specific Fc effector function early in infection predicts the development of broadly neutralizing antibodies.

    Directory of Open Access Journals (Sweden)

    Simone I Richardson

    2018-04-01

    Full Text Available While the induction of broadly neutralizing antibodies (bNAbs is a major goal of HIV vaccination strategies, there is mounting evidence to suggest that antibodies with Fc effector function also contribute to protection against HIV infection. Here we investigated Fc effector functionality of HIV-specific IgG plasma antibodies over 3 years of infection in 23 individuals, 13 of whom developed bNAbs. Antibody-dependent cellular phagocytosis (ADCP, complement deposition (ADCD, cellular cytotoxicity (ADCC and cellular trogocytosis (ADCT were detected in almost all individuals with levels of activity increasing over time. At 6 months post-infection, individuals with bNAbs had significantly higher levels of ADCD and ADCT that correlated with antibody binding to C1q and FcγRIIa respectively. In addition, antibodies from individuals with bNAbs showed more IgG subclass diversity to multiple HIV antigens which also correlated with Fc polyfunctionality. Germinal center activity represented by CXCL13 levels and expression of activation-induced cytidine deaminase (AID was found to be associated with neutralization breadth, Fc polyfunctionality and IgG subclass diversity. Overall, multivariate analysis by random forest classification was able to group bNAb individuals with 85% sensitivity and 80% specificity based on the properties of their antibody Fc early in HIV infection. Thus, the Fc effector function profile predicted the development of neutralization breadth in this cohort, suggesting that intrinsic immune factors within the germinal center provide a mechanistic link between the Fc and Fab of HIV-specific antibodies.

  18. Cooling Performance of a Partially-Confined FC-72 Spray: The Effect of Dissolved Air (Postprint)

    Science.gov (United States)

    2007-01-01

    plate FC = FC-72 fluid htr = heater conductive layer int = interface between heater substrate and insulating support post m = measured s = heater... microporous enhanced surface and a plain reference surface, and developed correlations for nucleate boiling and CHF. The results of the experiment...8Rainey, K. N., You, S. M., and Lee, S., “Effect of Pressure, Subcooling, and Dissolved Gas on Pool Boiling Heat Transfer from Microporous Surfaces

  19. HIV-specific Fc effector function early in infection predicts the development of broadly neutralizing antibodies.

    Science.gov (United States)

    Richardson, Simone I; Chung, Amy W; Natarajan, Harini; Mabvakure, Batsirai; Mkhize, Nonhlanhla N; Garrett, Nigel; Abdool Karim, Salim; Moore, Penny L; Ackerman, Margaret E; Alter, Galit; Morris, Lynn

    2018-04-01

    While the induction of broadly neutralizing antibodies (bNAbs) is a major goal of HIV vaccination strategies, there is mounting evidence to suggest that antibodies with Fc effector function also contribute to protection against HIV infection. Here we investigated Fc effector functionality of HIV-specific IgG plasma antibodies over 3 years of infection in 23 individuals, 13 of whom developed bNAbs. Antibody-dependent cellular phagocytosis (ADCP), complement deposition (ADCD), cellular cytotoxicity (ADCC) and cellular trogocytosis (ADCT) were detected in almost all individuals with levels of activity increasing over time. At 6 months post-infection, individuals with bNAbs had significantly higher levels of ADCD and ADCT that correlated with antibody binding to C1q and FcγRIIa respectively. In addition, antibodies from individuals with bNAbs showed more IgG subclass diversity to multiple HIV antigens which also correlated with Fc polyfunctionality. Germinal center activity represented by CXCL13 levels and expression of activation-induced cytidine deaminase (AID) was found to be associated with neutralization breadth, Fc polyfunctionality and IgG subclass diversity. Overall, multivariate analysis by random forest classification was able to group bNAb individuals with 85% sensitivity and 80% specificity based on the properties of their antibody Fc early in HIV infection. Thus, the Fc effector function profile predicted the development of neutralization breadth in this cohort, suggesting that intrinsic immune factors within the germinal center provide a mechanistic link between the Fc and Fab of HIV-specific antibodies.

  20. A soluble form of the high affinity IgE receptor, Fc-epsilon-RI, circulates in human serum.

    Directory of Open Access Journals (Sweden)

    Eleonora Dehlink

    Full Text Available Soluble IgE receptors are potential in vivo modulators of IgE-mediated immune responses and are thus important for our basic understanding of allergic responses. We here characterize a novel soluble version of the IgE-binding alpha-chain of Fc-epsilon-RI (sFcεRI, the high affinity receptor for IgE. sFcεRI immunoprecipitates as a protein of ∼40 kDa and contains an intact IgE-binding site. In human serum, sFcεRI is found as a soluble free IgE receptor as well as a complex with IgE. Using a newly established ELISA, we show that serum sFcεRI levels correlate with serum IgE in patients with elevated IgE. We also show that serum of individuals with normal IgE levels can be found to contain high levels of sFcεRI. After IgE-antigen-mediated crosslinking of surface FcεRI, we detect sFcεRI in the exosome-depleted, soluble fraction of cell culture supernatants. We further show that sFcεRI can block binding of IgE to FcεRI expressed at the cell surface. In summary, we here describe the alpha-chain of FcεRI as a circulating soluble IgE receptor isoform in human serum.

  1. Imaging and measuring the biophysical properties of Fc gamma receptors on single macrophages using atomic force microscopy

    Energy Technology Data Exchange (ETDEWEB)

    Li, Mi [State Key Laboratory of Robotics, Shenyang Institute of Automation, Chinese Academy of Sciences, Shenyang 110016 (China); University of Chinese Academy of Sciences, Beijing 100049 (China); Liu, Lianqing, E-mail: lqliu@sia.cn [State Key Laboratory of Robotics, Shenyang Institute of Automation, Chinese Academy of Sciences, Shenyang 110016 (China); Xi, Ning [Department of Mechanical and Biomedical Engineering, City University of Hong Kong, Hong Kong (China); Wang, Yuechao [State Key Laboratory of Robotics, Shenyang Institute of Automation, Chinese Academy of Sciences, Shenyang 110016 (China); Xiao, Xiubin [Department of Lymphoma, Affiliated Hospital of Military Medical Academy of Sciences, Beijing 100071 (China); Zhang, Weijing, E-mail: zhangwj3072@163.com [Department of Lymphoma, Affiliated Hospital of Military Medical Academy of Sciences, Beijing 100071 (China)

    2013-09-06

    Highlights: •Nanoscale cellular ultra-structures of macrophages were observed. •The binding affinities of FcγRs were measured directly on macrophages. •The nanoscale distributions of FcγRs were mapped on macrophages. -- Abstract: Fc gamma receptors (FcγR), widely expressed on effector cells (e.g., NK cells, macrophages), play an important role in clinical cancer immunotherapy. The binding of FcγRs to the Fc portions of antibodies that are attached to the target cells can activate the antibody-dependent cell-mediated cytotoxicity (ADCC) killing mechanism which leads to the lysis of target cells. In this work, we used atomic force microscopy (AFM) to observe the cellular ultra-structures and measure the biophysical properties (affinity and distribution) of FcγRs on single macrophages in aqueous environments. AFM imaging was used to obtain the topographies of macrophages, revealing the nanoscale cellular fine structures. For molecular interaction recognition, antibody molecules were attached onto AFM tips via a heterobifunctional polyethylene glycol (PEG) crosslinker. With AFM single-molecule force spectroscopy, the binding affinities of FcγRs were quantitatively measured on single macrophages. Adhesion force mapping method was used to localize the FcγRs, revealing the nanoscale distribution of FcγRs on local areas of macrophages. The experimental results can improve our understanding of FcγRs on macrophages; the established approach will facilitate further research on physiological activities involved in antibody-based immunotherapy.

  2. Ligand binding and antigenic properties of a human neonatal Fc receptor with mutation of two unpaired cysteine residues

    DEFF Research Database (Denmark)

    Andersen, Jan T; Justesen, Sune; Fleckenstein, Burkhard

    2008-01-01

    knowledge gives incentives for the design of IgG and albumin-based diagnostics and therapeutics. To study FcRn in vitro and to select and characterize FcRn binders, large quantities of soluble human FcRn are needed. In this report, we explored the impact of two free cysteine residues (C48 and C251......) of the FcRn heavy chain on the overall structure and function of soluble human FcRn and described an improved bacterial production strategy based on removal of these residues, yielding approximately 70 mg.L(-1) of fermentation of refolded soluble human FcRn. The structural and functional integrity...... was proved by CD, surface plasmon resonance and MALDI-TOF peptide mapping analyses. The strategy may generally be translated to the large-scale production of other major histocompatibility complex class I-related molecules with nonfunctional unpaired cysteine residues. Furthermore, the anti-FcRn response...

  3. Differential Use of Human Neutrophil Fcγ Receptors for Inducing Neutrophil Extracellular Trap Formation.

    Science.gov (United States)

    Alemán, Omar Rafael; Mora, Nancy; Cortes-Vieyra, Ricarda; Uribe-Querol, Eileen; Rosales, Carlos

    2016-01-01

    Neutrophils (PMN) are the most abundant leukocytes in the blood. PMN migrate from the circulation to sites of infection, where they are responsible for antimicrobial functions. PMN use phagocytosis, degranulation, and formation of neutrophil extracellular traps (NETs) to kill microbes. NETs are fibers composed of chromatin and neutrophil-granule proteins. Several pathogens, including bacteria, fungi, and parasites, and also some pharmacological stimuli such as phorbol 12-myristate 13-acetate (PMA) are efficient inducers of NETs. Antigen-antibody complexes are also capable of inducing NET formation. However the particular Fcγ receptor involved in triggering this function is a matter of controversy. In order to provide some insight into what Fcγ receptor is responsible for NET formation, each of the two human Fcγ receptors was stimulated individually by specific monoclonal antibodies and NET formation was evaluated. FcγRIIa cross-linking did not promote NET formation. Cross-linking other receptors such as integrins also did not promote NET formation. In contrast FcγRIIIb cross-linking induced NET formation similarly to PMA stimulation. NET formation was dependent on NADPH-oxidase, PKC, and ERK activation. These data show that cross-linking FcγRIIIb is responsible for NET formation by the human neutrophil.

  4. Differential Use of Human Neutrophil Fcγ Receptors for Inducing Neutrophil Extracellular Trap Formation

    Directory of Open Access Journals (Sweden)

    Omar Rafael Alemán

    2016-01-01

    Full Text Available Neutrophils (PMN are the most abundant leukocytes in the blood. PMN migrate from the circulation to sites of infection, where they are responsible for antimicrobial functions. PMN use phagocytosis, degranulation, and formation of neutrophil extracellular traps (NETs to kill microbes. NETs are fibers composed of chromatin and neutrophil-granule proteins. Several pathogens, including bacteria, fungi, and parasites, and also some pharmacological stimuli such as phorbol 12-myristate 13-acetate (PMA are efficient inducers of NETs. Antigen-antibody complexes are also capable of inducing NET formation. However the particular Fcγ receptor involved in triggering this function is a matter of controversy. In order to provide some insight into what Fcγ receptor is responsible for NET formation, each of the two human Fcγ receptors was stimulated individually by specific monoclonal antibodies and NET formation was evaluated. FcγRIIa cross-linking did not promote NET formation. Cross-linking other receptors such as integrins also did not promote NET formation. In contrast FcγRIIIb cross-linking induced NET formation similarly to PMA stimulation. NET formation was dependent on NADPH-oxidase, PKC, and ERK activation. These data show that cross-linking FcγRIIIb is responsible for NET formation by the human neutrophil.

  5. NRG1-Fc improves metabolic health via dual hepatic and central action.

    Science.gov (United States)

    Zhang, Peng; Kuang, Henry; He, Yanlin; Idiga, Sharon O; Li, Siming; Chen, Zhimin; Yang, Zhao; Cai, Xing; Zhang, Kezhong; Potthoff, Matthew J; Xu, Yong; Lin, Jiandie D

    2018-03-08

    Neuregulins (NRGs) are emerging as an important family of signaling ligands that regulate glucose and lipid homeostasis. NRG1 lowers blood glucose levels in obese mice, whereas the brown fat-enriched secreted factor NRG4 protects mice from high-fat diet-induced insulin resistance and hepatic steatosis. However, the therapeutic potential of NRGs remains elusive, given the poor plasma half-life of the native ligands. Here, we engineered a fusion protein using human NRG1 and the Fc domain of human IgG1 (NRG1-Fc) that exhibited extended half-life in circulation and improved potency in receptor signaling. We evaluated its efficacy in improving metabolic parameters and dissected the mechanisms of action. NRG1-Fc treatment triggered potent AKT activation in the liver, lowered blood glucose, improved insulin sensitivity, and suppressed food intake in obese mice. NRG1-Fc acted as a potent secretagogue for the metabolic hormone FGF21; however, the latter was largely dispensable for its metabolic effects. NRG1-Fc directly targeted the hypothalamic POMC neurons to promote membrane depolarization and increase firing rate. Together, NRG1-Fc exhibits improved pharmacokinetic properties and exerts metabolic benefits through dual inhibition of hepatic gluconeogenesis and caloric intake.

  6. Effects of Hyporheic Water Fluxes and Sediment Grain Size on the Concentration and Diffusive Flux of Heavy Metals in the Streambed.

    Science.gov (United States)

    Liu, Qi; Song, Jinxi; Zhang, Guotao; Wang, Weize; Guo, Weiqiang; Tang, Bin; Kong, Feihe; Huo, Aidi

    2017-09-06

    The hyporheic zone regulates physicochemical processes in surface-groundwater systems and can be an important source of heavy metals in fluvial systems. This study assesses the pore water concentrations and diffusive fluxes of heavy metals with respect to the vertical water exchange flux (VWEF) and sediment grain size. Water and sediment samples were collected on August 2016 from upstream Site 1 and downstream Site 2 along the Juehe River in Shaanxi Province, China. Streambed vertical hydraulic conductivity (Kv) and the VWEF were estimated via the standpipe permeameter test method and Darcy's law. The heavy metal concentrations in the pore water were measured and the diffusive fluxes were calculated using Fick's first law. The VWEF patterns were dominated by upward flow, and Site 1 featured higher values of Kv and VWEF. Higher Cu and Zn concentrations occurred near the channel centre with coarse sand and gravel and greater upward VWEFs because coarser sediment and greater upward VWEFs cause stronger metal desorption capacity. Additionally, Cu and Zn at the two sites generally diffused from pore water to surface water, potentially due to the upward VWEF. The VWEF and sediment grain size are likely crucial factors influencing the heavy metal concentrations and diffusive fluxes.

  7. Does upward mobility result in greater well-being? Evidence from a pre-registered study on a large population-based survey

    OpenAIRE

    Cheung, Felix; Jackson, Joshua; Hill, Patrick

    2017-01-01

    Income inequality gained increasing attention in public discourse. Promoting upward mobility is a potential solution to income inequality. The current study tested whether upward mobility predicts greater well-being, whether upward mobility attenuates the negative effects of income inequality, and whether gender differences in upward mobility differentially predict well-being for men and women. Upward mobility was operationalized as changes in income rank across generations for families in th...

  8. High-flux solar concentration with imaging designs

    Energy Technology Data Exchange (ETDEWEB)

    Feuermann, D. [Ben-Gurion University of the Negev (Israel). Jacob Blaustein Institute for Desert Research; Gordon, J.M. [Ben-Gurion University of the Negev (Israel). Jacob Blaustein Institute for Desert Research; Ben-Gurion University of the Negev (Israel). Dept. of Mechanical Engineering; Ries, H. [Ries and Partners, Munich (Germany)

    1999-02-01

    Most large solar concentrators designed for high flux concentration at high collection efficiency are based on imaging primary mirrors and nonimaging secondary concentrators. In this paper, we offer an alternative purely imaging two-stage solar concentrator that can attain high flux concentration at high collection efficiency. Possible practical virtues include: (1) an inherent large gap between absorber and secondary mirror; (2) a restricted angular range on the absorber; and (3) an upward-facing receiver where collected energy can be extracted via the (shaded) apex of the parabola. We use efficiency-concentration plots to characterize the solar concentrators considered, and to evaluate the potential improvements with secondary concentrators. (author)

  9. 34 CFR 645.20 - How many applications for an Upward Bound award may an eligible applicant submit?

    Science.gov (United States)

    2010-07-01

    ... 34 Education 3 2010-07-01 2010-07-01 false How many applications for an Upward Bound award may an eligible applicant submit? 645.20 Section 645.20 Education Regulations of the Offices of the Department of... Does One Apply for An Award? § 645.20 How many applications for an Upward Bound award may an eligible...

  10. 77 FR 21089 - Notice of Submission for OMB Review; Application for Grants Under the Upward Bound Math and...

    Science.gov (United States)

    2012-04-09

    ... Upward Bound Math and Science Program AGENCY: Office of Postsecondary Education, Department of Education. SUMMARY: The Upward Bound Math and Science (UBMS) program provides grants to institutions of higher... for success in a program of postsecondary education that lead to careers in math and science. DATES...

  11. Measurement of the rate of droplet deposition in vertical upward and downward annular flows

    International Nuclear Information System (INIS)

    Murakami, Toshihiro; Okawa, Tomio; Takei, Rei

    2008-01-01

    The deposition rate of droplets was measured for vertical annular two-phase flows in a small diameter tube by means of the double film extraction technique. The test section was a round tube of 5 mm in inside diameter, air and water were used as test fluids, and the flow direction was set to upward and downward; the system pressure and the flow rates of gas and liquid phases were changed parametrically. If the droplet velocity relative to the continuous gas phase is in the equilibrium state, the shear induced lift force acting on droplets is directed toward the tube centerline in upflow while toward the tube wall in downflow. Particular attention was therefore paid to the effect of flow direction. It was shown experimentally that the deposition rate of droplets in downward flow is greater than that in upward flow. The difference in the measured deposition rate may be attributed to the direction of lift force acting on droplets. (author)

  12. Contribution of PIP-5 kinase Iα to raft-based FcγRIIA signaling

    International Nuclear Information System (INIS)

    Szymanska, Ewelina; Korzeniowski, Marek; Raynal, Patrick; Sobota, Andrzej; Kwiatkowska, Katarzyna

    2009-01-01

    Receptor FcγIIA (FcγRIIA) associates with plasma membrane rafts upon activation to trigger signaling cascades leading to actin polymerization. We examined whether compartmentalization of PI(4,5)P 2 and PI(4,5)P 2 -synthesizing PIP5-kinase Iα to rafts contributes to FcγRIIA signaling. A fraction of PIP5-kinase Iα was detected in raft-originating detergent-resistant membranes (DRM) isolated from U937 monocytes and other cells. The DRM of U937 monocytes contained also a major fraction of PI(4,5)P 2 . PIP5-kinase Iα bound PI(4,5)P 2 , and depletion of the lipid displaced PIP5-kinase Iα from the DRM. Activation of FcγRIIA in BHK transfectants led to recruitment of the kinase to the plasma membrane and enrichment of DRM in PI(4,5)P 2 . Immunofluorescence studies revealed that in resting cells the kinase was associated with the plasma membrane, cytoplasmic vesicles and the nucleus. After FcγRIIA activation, PIP5-kinase Iα and PI(4,5)P 2 co-localized transiently with the activated receptor at distinct cellular locations. Immunoelectron microscopy studies revealed that PIP5-kinase Iα and PI(4,5)P 2 were present at the edges of electron-dense assemblies containing activated FcγRIIA in their core. The data suggest that activation of FcγRIIA leads to membrane rafts coalescing into signaling platforms containing PIP5-kinase Iα and PI(4,5)P 2

  13. CFD analysis using two-equation turbulence models for the vertical upward flow of water in a heated tube at supercritical pressure(I)

    International Nuclear Information System (INIS)

    Kim, Y. I.; Kim, S. H.; Bae, Y. Y.; Cho, B. H.

    2003-12-01

    Numerical simulation was performed referring to the Yamagata's experiment on the heat transfer in a vertical tube where water flows upward at supercritical pressure. Numerical simulation was performed for the conditions of tube diameter of 7.5 mm, heated tube length of 2 m, operation pressure at 245 bar, bulk temperatures from 300 to 420 .deg. C, heat fluxes from 465 to 930 kW/m 2 and mass velocity 1,260 kg/m 2 s, by Fluent code and compared with the Yamagata's experiments. At the heat flux 465 kW/m 2 , the maximum difference between calculated results and Yamagata's experiment were less than 20% and the difference between the results using different turbulence models was not so significant. But at the heat flux, 930 kW/m 2 , the difference between the calculations and Yamagata's experiment increased to about 25%, and the difference between the results using different turbulence models increased significantly. The case with RNG κ-ε and enhanced wall treatment predicted the Yamagata's experiment best

  14. Freezing of aluminium oxide and iron flowing upward in circular quartz glass tubes

    International Nuclear Information System (INIS)

    Kuhn, D.; Moeschke, M.; Werle, H.

    1983-10-01

    The freezing of aluminium oxide and iron flowing upward in circular quartz glass tubes has been studied in a series of experiments. Several tubes were used in the same test. This demonstrated a good reproducibility and allowed systematic parameter variations, especially of the channel diameter. The time-dependance of the penetration was observed with a film camera and these date provide a good basis for a detailed check of sophisticated models which are in development. (orig.) [de

  15. Air-water upward flow in prismatic channel of rectangular base

    International Nuclear Information System (INIS)

    Carvalho Tofani, P. de.

    1984-01-01

    Experiments had carried out to investigate the two-phase upward air-water flow structure, in a rectangular test section, by using independent measuring techniques, which comprise direct viewing and photography, electrical probes and gamma-ray attenuation. Flow pattern maps and correlations for flow pattern transitions, void fraction profiles, liquid film thickness and superficial average void fraction are proposed and compared to available data. (Author) [pt

  16. The transition from flooding to upwards cocurrent annular flow in a vertical pipe

    International Nuclear Information System (INIS)

    Wallis, G.B.

    1962-02-01

    The limits of countercurrent flow in a vertical pipe are related to the onset of cocurrent upwards annual flow. The results are confirmed by evidence from several sources and lead to the criterion v g =(0.8→0.9)p g -1/2 [D g (p f -p g )] 1/2 for the minimum gas superficial velocity which will support a liquid film in concurrent flow. (author)

  17. Downstream lightening and upward heavying, sorting of sediments of uniform grain size but differing in density

    Science.gov (United States)

    Viparelli, E.; Solari, L.; Hill, K. M.

    2014-12-01

    Downstream fining, i.e. the tendency for a gradual decrease in grain size in the downstream direction, has been observed and studied in alluvial rivers and in laboratory flumes. Laboratory experiments and field observations show that the vertical sorting pattern over a small Gilbert delta front is characterized by an upward fining profile, with preferential deposition of coarse particles in the lowermost part of the deposit. The present work is an attempt to answer the following questions. Are there analogous sorting patterns in mixtures of sediment particles having the same grain size but differing density? To investigate this, we performed experiments at the Hydrosystems Laboratory at the University of Illinois at Urbana-Champaign. During the experiments a Gilbert delta formed and migrated downstream allowing for the study of transport and sorting processes on the surface and within the deposit. The experimental results show 1) preferential deposition of heavy particles in the upstream part of the deposit associated with a pattern of "downstream lightening"; and 2) a vertical sorting pattern over the delta front characterized by a pattern of "upward heavying" with preferential deposition of light particles in the lowermost part of the deposit. The observed downstream lightening is analogous of the downstream fining with preferential deposition of heavy (coarse) particles in the upstream part of the deposit. The observed upward heavying was unexpected because, considering the particle mass alone, the heavy (coarse) particles should have been preferentially deposited in the lowermost part of the deposit. Further, the application of classical fractional bedload transport relations suggests that in the case of mixtures of particles of uniform size and different densities equal mobility is not approached. We hypothesize that granular physics mechanisms traditionally associated with sheared granular flows may be responsible for the observed upward heavying and for the

  18. Warming-induced upward migration of the alpine treeline in the Changbai Mountains, northeast China.

    Science.gov (United States)

    Du, Haibo; Liu, Jie; Li, Mai-He; Büntgen, Ulf; Yang, Yue; Wang, Lei; Wu, Zhengfang; He, Hong S

    2018-03-01

    Treeline responses to environmental changes describe an important phenomenon in global change research. Often conflicting results and generally too short observations are, however, still challenging our understanding of climate-induced treeline dynamics. Here, we use a state-of-the-art dendroecological approach to reconstruct long-term changes in the position of the alpine treeline in relation to air temperature at two sides in the Changbai Mountains in northeast China. Over the past 160 years, the treeline increased by around 80 m, a process that can be divided into three phases of different rates and drives. The first phase was mainly influenced by vegetation recovery after an eruption of the Tianchi volcano in 1702. The slowly upward shift in the second phase was consistent with the slowly increasing temperature. The last phase coincided with rapid warming since 1985, and shows with 33 m per 1°C, the most intense upward shift. The spatial distribution and age structure of trees beyond the current treeline confirm the latest, warming-induced upward shift. Our results suggest that the alpine treeline will continue to rise, and that the alpine tundra may disappear if temperatures will increase further. This study not only enhances mechanistic understanding of long-term treeline dynamics, but also highlights the effects of rising temperatures on high-elevation vegetation dynamics. © 2017 John Wiley & Sons Ltd.

  19. Experimental study on liquid velocity in upward and downward two-phase flows

    International Nuclear Information System (INIS)

    Sun, X.; Paranjape, S.; Kim, S.; Ozar, B.; Ishii, M.

    2003-01-01

    Local characteristics of the liquid phase in upward and downward air-water two-phase flows were experimentally investigated in a 50.8-mm inner-diameter round pipe. An integral Laser Doppler Anemometry (LDA) system was used to measure the axial liquid velocity and its fluctuations. No effect of the flow direction on the liquid velocity radial profile was observed in single-phase liquid benchmark experiments. Local multi-sensor conductivity probes were used to measure the radial profiles of the bubble velocity and the void fraction. The measurement results in the upward and downward two-phase flows are compared and discussed. The results in the downward flow demonstrated that the presence of the bubbles tended to flatten the liquid velocity radial profile, and the maximum liquid velocity could occur off the pipe centerline, in particular at relatively low flow rates. However, the maximum liquid velocity always occurred at the pipe center in the upward flow. Also, noticeable turbulence enhancement due to the bubbles in the two-phase flows was observed in the current experimental flow conditions. Furthermore, the distribution parameter and the void weighted area-averaged drift velocity were obtained based on the definitions

  20. Interfacial structures and area transport in upward and downward two-phase flow

    International Nuclear Information System (INIS)

    Paranjape, S. S.; Kim, S.; Ishii, M.; Kelly, J.

    2003-01-01

    An experimental study has been carried out for upward and downward two-phase flow to study local interfacial structures and interfacial area transport. The flow studied, is an adiabatic, air-water, co-current, two-phase flow, in 25.4 mm and 50.8 mm ID test sections. Flow regime map is obtained using the characteristic signals obtained from an impedance void meter, employing neural network based identification methodology. A four sensor conductivity probe is used to measure the local two phase flow parameters, in bubbly flow regime. The local profiles of these parameters as well as their axial development reveal the nature of the interfacial structures and the bubble interaction mechanisms occurring in the flow. Furthermore, this study provides a good database for the development of the interfacial area transport equation, which dynamically models the changes in the interfacial area along a flow field. An interfacial area transport equation is used for downward flow based on that developed for the upward flow, with certain modifications in the bubble interaction terms. The area averaged values of the interfacial area concentration are compared with those predicted by the interfacial area transport model. The differences in the interfacial structures and interfacial area transport in co-current downward and upward two-phase flows are studied

  1. Clinical Assessment of Scapula Motion: Scapula Upward Rotation and Relationship with Injury in Swimmers

    Directory of Open Access Journals (Sweden)

    Jo Brown

    2016-01-01

    Full Text Available Abnormal scapulothoracic mechanics and scapulohumeral rhythm are implicated in shoulder pathologies, including glenohumeral impingement and rotator cuff tears. Upward scapula rotation, specifically asymmetry of scapula motion and associations of patterns through range with injury, was investigated in dominant and non-dominant limbs of nationally ranked junior and Paralympic swimmers during competition season. The static and throughout phases measures of upward scapula rotation were: Phase I (start position, 45°, Phase II (45° to 90°, Phase III (90° to 135° and Phase IV (135° to max. Injury was assessed with a validated questionnaire. Differences between side (dominant and non-dominant, group (junior and Paralympic, and phase were examined. Significant differences (P < 0.05 between groups were identified for dominant side at rest, 45° and 135°, and in phases II and IV (including range. Scapulohumeral rhythm was higher in the non-dominant limb of Paralympic swimmers but in the dominant limb of junior swimmers. Greatest differences in upward rotation between injured and non-injured swimmers were found in Phase 1: 43.6% (3.3° Paralympic; 73.1% (8° junior. Results suggest asymmetry of movement in both limbs, through all phases, and at single points in range, should be investigated for assessing injury and developing preventive strategies and rehabilitation protocols.

  2. Human disturbance and upward expansion of plants in a warming climate

    Science.gov (United States)

    Dainese, Matteo; Aikio, Sami; Hulme, Philip E.; Bertolli, Alessio; Prosser, Filippo; Marini, Lorenzo

    2017-08-01

    Climate change is expected to trigger an upward expansion of plants in mountain regions and, although there is strong evidence that many native species have already shifted their distributions to higher elevations, little is known regarding how fast non-native species might respond to climate change. By analysing 131,394 occurrence records of 1,334 plant species collected over 20 years in the European Alps, we found that non-natives are spreading upwards approximately twice as fast as natives. Whereas the spread of natives was enhanced by traits favouring longer dispersal distances, this was not the case for non-natives. This was due to the non-native species pool already being strongly biased towards species that had traits facilitating spread. A large proportion of native and non-native species seemed to be able to spread upwards faster than the current velocity of climate change. In particular, long-distance dispersal events and proximity to roads proved to be key drivers for the observed rapid spread. Our findings highlight that invasions by non-native species into native alpine communities are a potentially significant additional pressure on these vulnerable ecosystems that are already likely to suffer dramatic vegetation changes with ongoing warming and increasing human activity in mountain regions.

  3. CHROMOSPHERIC AND CORONAL WAVE GENERATION IN A MAGNETIC FLUX SHEATH

    International Nuclear Information System (INIS)

    Kato, Yoshiaki; Hansteen, Viggo; Gudiksen, Boris; Wedemeyer, Sven; Carlsson, Mats; Steiner, Oskar

    2016-01-01

    Using radiation magnetohydrodynamic simulations of the solar atmospheric layers from the upper convection zone to the lower corona, we investigate the self-consistent excitation of slow magneto-acoustic body waves (slow modes) in a magnetic flux concentration. We find that the convective downdrafts in the close surroundings of a two-dimensional flux slab “pump” the plasma inside it in the downward direction. This action produces a downflow inside the flux slab, which encompasses ever higher layers, causing an upwardly propagating rarefaction wave. The slow mode, excited by the adiabatic compression of the downflow near the optical surface, travels along the magnetic field in the upward direction at the tube speed. It develops into a shock wave at chromospheric heights, where it dissipates, lifts the transition region, and produces an offspring in the form of a compressive wave that propagates further into the corona. In the wake of downflows and propagating shock waves, the atmosphere inside the flux slab in the chromosphere and higher tends to oscillate with a period of ν ≈ 4 mHz. We conclude that this process of “magnetic pumping” is a most plausible mechanism for the direct generation of longitudinal chromospheric and coronal compressive waves within magnetic flux concentrations, and it may provide an important heat source in the chromosphere. It may also be responsible for certain types of dynamic fibrils.

  4. CHROMOSPHERIC AND CORONAL WAVE GENERATION IN A MAGNETIC FLUX SHEATH

    Energy Technology Data Exchange (ETDEWEB)

    Kato, Yoshiaki; Hansteen, Viggo; Gudiksen, Boris; Wedemeyer, Sven; Carlsson, Mats [Institute of Theoretical Astrophysics, University of Oslo, P.O. Box 1029 Blindern, NO-0315 Oslo (Norway); Steiner, Oskar, E-mail: yoshiaki.kato@astro.uio.no [Kiepenheuer-Institut für Sonnenphysik, Schöneckstrasse 6, D-79104 Freiburg (Germany)

    2016-08-10

    Using radiation magnetohydrodynamic simulations of the solar atmospheric layers from the upper convection zone to the lower corona, we investigate the self-consistent excitation of slow magneto-acoustic body waves (slow modes) in a magnetic flux concentration. We find that the convective downdrafts in the close surroundings of a two-dimensional flux slab “pump” the plasma inside it in the downward direction. This action produces a downflow inside the flux slab, which encompasses ever higher layers, causing an upwardly propagating rarefaction wave. The slow mode, excited by the adiabatic compression of the downflow near the optical surface, travels along the magnetic field in the upward direction at the tube speed. It develops into a shock wave at chromospheric heights, where it dissipates, lifts the transition region, and produces an offspring in the form of a compressive wave that propagates further into the corona. In the wake of downflows and propagating shock waves, the atmosphere inside the flux slab in the chromosphere and higher tends to oscillate with a period of ν ≈ 4 mHz. We conclude that this process of “magnetic pumping” is a most plausible mechanism for the direct generation of longitudinal chromospheric and coronal compressive waves within magnetic flux concentrations, and it may provide an important heat source in the chromosphere. It may also be responsible for certain types of dynamic fibrils.

  5. Cleavage of the interchain disulfide bonds in rituximab increases its affinity for FcγRIIIA.

    Science.gov (United States)

    Suzuki, Mami; Yamanoi, Ayaka; Machino, Yusuke; Kobayashi, Eiji; Fukuchi, Kaori; Tsukimoto, Mitsutoshi; Kojima, Shuji; Kohroki, Junya; Akimoto, Kazunori; Masuho, Yasuhiko

    2013-07-05

    The Fc region of human IgG1 mediates effector function via binding to Fcγ receptors and complement activation. The H and L chains of IgG1 antibodies are joined by four interchain disulfide bonds. In this study, these bonds within the therapeutic IgG1 rituximab (RTX) were cleaved either by mild reduction followed by alkylation or by mild S-sulfonation; consequently, two modified RTXs - A-RTX (alkylated) and S-RTX (S-sulfonated) - were formed, and both were almost as potent as unmodified RTX when binding CD20 antigen. Unexpectedly, each modified RTX had a higher binding affinity for FcγRIIIA (CD16A) than did unmodified RTX. However, S-RTX and A-RTX were each less potent than RTX in an assay of antibody-dependent cellular cytotoxicity (ADCC). In this ADCC assay, each modified RTX showed decreased secretion of granzyme B, but no change in perforin secretion, from effector cells. These results provide significant information on the structures within IgG1 that are involved in binding FcγRIIIA, and they may be useful in the development of therapeutic antagonists for FcγRIIIA. Copyright © 2013 Elsevier Inc. All rights reserved.

  6. Fc-Binding Ligands of Immunoglobulin G: An Overview of High Affinity Proteins and Peptides

    Directory of Open Access Journals (Sweden)

    Weonu Choe

    2016-12-01

    Full Text Available The rapidly increasing application of antibodies has inspired the development of several novel methods to isolate and target antibodies using smart biomaterials that mimic the binding of Fc-receptors to antibodies. The Fc-binding domain of antibodies is the primary binding site for e.g., effector proteins and secondary antibodies, whereas antigens bind to the Fab region. Protein A, G, and L, surface proteins expressed by pathogenic bacteria, are well known to bind immunoglobulin and have been widely exploited in antibody purification strategies. Several difficulties are encountered when bacterial proteins are used in antibody research and application. One of the major obstacles hampering the use of bacterial proteins is sample contamination with trace amounts of these proteins, which can invoke an immune response in the host. Many research groups actively develop synthetic ligands that are able to selectively and strongly bind to antibodies. Among the reported ligands, peptides that bind to the Fc-domain of antibodies are attractive tools in antibody research. Besides their use as high affinity ligands in antibody purification chromatography, Fc-binding peptides are applied e.g., to localize antibodies on nanomaterials and to increase the half-life of proteins in serum. In this review, recent developments of Fc-binding peptides are presented and their binding characteristics and diverse applications are discussed.

  7. Bacteria and viruses modulate FcεRI-dependent mast cell activity 

    Directory of Open Access Journals (Sweden)

    Aleksandra Słodka

    2013-03-01

    Full Text Available Undoubtedly, mast cells play a central role in allergic processes. Specific allergen cross-linking of IgE bound to the high affinity receptors (FcεRI on the mast cell surface leads to the release of preformed mediators and newly synthesized mediators, i.e. metabolites of arachidonic acid and cytokines. More and more data indicate that bacteria and viruses can influence FcεRI-dependent mast cell activation. Some bacterial and viral components can reduce the surface expression of FcεRI. There are also findings that ligation of Toll-like receptors (TLRs by bacterial or viral antigens can affect IgE-dependent mast cell degranulation and preformed mediator release as well as eicosanoid production. The synergistic interaction of TLR ligands and allergen can also modify cytokine synthesis by mast cells stimulated via FcεRI. Moreover, data suggest that specific IgE for bacterial or viral antigens can influence mast cell activity. What is more, some bacterial and viral components or some endogenous proteins produced during viral infection can act as superantigens by interacting with the VH3 domain of IgE. All these observations indicate that bacterial and viral infections modify the course of allergic diseases by affecting FcεRI-dependent mast cell activation. 

  8. Site-selective conjugation of an anticoagulant aptamer to recombinant albumins and maintenance of neonatal Fc receptor binding

    DEFF Research Database (Denmark)

    Schmøkel, Julie; Voldum, Anders; Tsakiridou, Georgia

    2017-01-01

    -linked aptamer to that of aptamer alone was found using an anticoagulant activity assay measuring temporal levels of activated partial thrombin. Covalent albumin-aptamer conjugation, however, substantially compromized binding to hFcRn, to 10% affinity of that of non-conjugated WT, determined by biolayer......-life, predominately facilitated by engagement with the cellular recycling neonatal Fc receptor (FcRn), and ligand transport properties of albumin promote it as an attractive candidate to improve the pharmacokinetic profile of aptamers. This study investigates the effect of Cys34 site-selective covalent attachment...... of a factor IXa anticoagulant aptamer on aptamer functionality and human FcRn (hFcRn) engagement using recombinant human albumin (rHA) of either a wild type (WT) or an engineered human FcRn high binding variant (HB). Albumin-aptamer conjugates, connected covalently through a heterobifunctional succinimidyl 4...

  9. Functional characterization of the high affinity IgG Receptor : making heads and tails of FcγRI

    NARCIS (Netherlands)

    van der Poel, C.E.

    2011-01-01

    This thesis focuses on human FcγRI, a high affinity receptor for antibodies of the IgG isotype. IgG is the most abundant antibody type in blood and all currently FDA approved therapeutic antibodies are of the IgG isotype. FcγRI, a member of the activating Fcγ receptors, exists as a complex of a

  10. Glycoprotein VI/Fc receptor γ chain-independent tyrosine phosphorylation and activation of murine platelets by collagen

    OpenAIRE

    Jarvis, Gavin E.; Best, Denise; Watson, Steve P.

    2004-01-01

    We have investigated the ability of collagen to induce signalling and functional responses in suspensions of murine platelets deficient in the FcRγ (Fc receptor γ) chain, which lack the collagen receptor GPVI (glycoprotein VI). In the absence of the FcRγ chain, collagen induced a unique pattern of tyrosine phosphorylation which was potentiated by the thromboxane analogue U46619. Immunoprecipitation studies indicated that neither collagen alone nor the combination of collagen plus U46619 induc...

  11. Vertical nitrogen flux from the oceanic photic zone by diel migrant zooplankton and nekton

    Science.gov (United States)

    Longhurst, Alan R.; Glen Harrison, W.

    1988-06-01

    Where the photic zone is a biological steady-state, the downward flux of organic material across the pycnocline to the interior of the ocean is thought to be balanced by upward turbulent flux of inorganic nitrogen across the nutricline. This model ignores a significant downward dissolved nitrogen flux caused by the diel vertical migration of interzonal zooplankton and nekton that feed in the photic zone at night and excrete nitrogenous compounds at depth by day. In the oligotrophic ocean this flux can be equivalent to the flux of particulate organic nitrogen from the photic zone in the form of faecal pellets and organic flocculates. Where nitrogen is the limiting plant nutrient, and the flux by diel migration of interzonal plankton is significant compared to other nitrogen exports from the photic zone, there must be an upward revision of previous estimates for the ratio of new to total primary production in the photic zone if a nutrient balance is to be maintained. This upward revision is of the order 5-100% depending on the oceanographic regime.

  12. Magnetic-flux pump

    Science.gov (United States)

    Hildebrandt, A. F.; Elleman, D. D.; Whitmore, F. C. (Inventor)

    1966-01-01

    A magnetic flux pump is described for increasing the intensity of a magnetic field by transferring flux from one location to the magnetic field. The device includes a pair of communicating cavities formed in a block of superconducting material, and a piston for displacing the trapped magnetic flux into the secondary cavity producing a field having an intense flux density.

  13. Radon flux measurement methodologies

    International Nuclear Information System (INIS)

    Nielson, K.K.; Rogers, V.C.

    1984-01-01

    Five methods for measuring radon fluxes are evaluated: the accumulator can, a small charcoal sampler, a large-area charcoal sampler, the ''Big Louie'' charcoal sampler, and the charcoal tent sampler. An experimental comparison of the five flux measurement techniques was also conducted. Excellent agreement was obtained between the measured radon fluxes and fluxes predicted from radium and emanation measurements

  14. Hubungan Polimorfisme Gen FcγRIIA dengan Densitas P. falciparum dan Efikasi Dihidroartemisinin-Piperakuin

    Directory of Open Access Journals (Sweden)

    Sylvia Sance Marantina

    2016-06-01

    Full Text Available Dimorfisme FcγRlla memiliki keterkaitan dengan kemampuan inang dalam mengeliminasi parasit malaria sehingga perlu dilakukan penelitian untuk mengetahui polimorfisme alel FcγRlla dari populasi di daerah endemis malaria di Indonesia agar dapat diketahui peran imunitas dalam mengeliminasi parasit malaria. Sebanyak 120 sampel dried blood spot (DBS malaria falsifarum yang diperoleh dari studi efikasi obat DHP di lima wilayah di Indonesia dianalisis dengan polymerase chain reaction (PCR dan sekuensing untuk melihat varian alel FcγRIIa-131 serta hubungannya dengan densitas parasit dan efikasi dihidroartemisinin-piperakuin. Analisis gen FcγRIIa menunjukkan bahwa genotip RH memiliki frekuensi paling tinggi (50,8% dibandingkan RR (17,5% dan HH (31,7%. Alel R131 gen FcγRIIa menunjukkan efek protektif terhadap high density parasitemia/HDP (>5000 parasit/μL; odds ratio [OR]= 0,133, 95% confidence interval [CI]= 0,053–0,334, p< 0,001 dan berhubungan dengan keberadaan gametosit yang lebih lama pada inang (>72 jam; relative risk [RR]= 1,571, 95% confidence interval [CI]= 1,005–2,456, p= 0,090. Kata Kunci: malaria falsiparum, dihidroartemisinin-piperakuin, K13, FcγRIIa, efikasi obat Polymorphism of Human FcγRIIa and Its Association with P. falciparum Density and Efficacy of Dihydroartemisinin- Piperaquine Abstract FcγRlla dimorphism has been related to the ability of the host to eliminate malaria parasite so it is necessary to investigate the allele polymorphism FcγRlla of population in malaria-endemic areas in Indonesia in order to know the role of immunity in eliminating malaria parasite. A total of 120 samples of Dried Blood Spot (DBS falciparum malaria acquired from DHP drug efficacy studies in 5 regions in Indonesia were analyzed by Polymerase Chain Reaction (PCR and sequencing, to look at variants of FcγRIIa-131 allele and its Association with Parasite DensityandEfficacy ofDihydroartemisinin- Piperaquine. The FcγRIIa gene analysis indicated

  15. (Some) Cellular Mechanisms Influencing the Transcription of Human Endogenous Retrovirus, HERV-Fc1

    DEFF Research Database (Denmark)

    Laska, Magdalena Janina; Nissen, Kari Konstantin; Nexø, Bjørn Andersen

    2013-01-01

    DNA methylation and histone acetylation are epigenetic modifications that act as regulators of gene expression. DNA methylation is considered an important mechanism for silencing of retroelements in the mammalian genome. However, the methylation of human endogenous retroviruses (HERVs) is not well...... investigated. The aim of this study was to investigate the transcriptional potential of HERV-Fc1 proviral 5'LTR in more detail, and examined the specific influence of CpG methylation on this LTR in number of cell lines. Specifically, the role of demethylating chemicals e.g. 5-aza-2' deoxycytidine...... and Trichostatin-A, in inducing or reactivating expression of HERV-Fc1 specific sequences and the mechanisms were investigated. In our present study, 5-aza-dC is shown to be a powerful inducer of HERV-Fc1, and at the same time it strongly inhibits methylation of DNA. Treatment with this demethylating agent 5-aza...

  16. Embryo-fetal transfer of bevacizumab (Avastin) in the rat over the course of gestation and the impact of neonatal Fc receptor (FcRn) binding.

    Science.gov (United States)

    Thorn, Mitchell; Piche-Nicholas, Nicole; Stedman, Donald; Davenport, Scott W; Zhang, Ning; Collinge, Mark; Bowman, Christopher J

    2012-10-01

    There is concern about embryo-fetal exposure to antibody-based biopharmaceuticals based on the increase of such therapies being prescribed to women of childbearing potential. Therefore, there is a desire to better characterize embryo-fetal exposure of these molecules. The pregnant rat is a standard model for evaluating the potential consequences of exposure but placental transfer of antibody-based biopharmaceuticals is not well understood in this model. The relative embryo-fetal distribution of an antibody-based biopharmaceutical was evaluated in the rat. Bevacizumab (Avastin) was chosen as a tool antibody since it does not have significant target binding in the rat that might influence embryo-fetal biodistribution. Avastin was labeled with a fluorescent dye, characterized, and injected into pregnant rats at different gestation ages. Labeled Avastin in fetal tissues was visualized ex vivo using an IVIS 200 (Caliper, A PerkinElmer Company, Alameda, CA). Avastin localized to the fetus as early as 24-hr post intravenous injection of the dam, and was taken up by the fetus in a dose-dependent manner. Avastin was detectable in the developing embryo as early as gestation day 13 and continued to be transferred until the end of gestation. Fetal transfer of Avastins mutated in the portion of the antibody that binds the neonatal Fc receptor (FcRn) was tested in late gestation and was found to correlate with affinities of the mutant Avastin antibody to FcRn. The novel application of this imaging technology was used to characterize the onset and duration of Avastin maternal-fetal transfer in rats and the importance of FcRn binding. © 2012 Wiley Periodicals, Inc.

  17. Endothelial Fcγ Receptor IIB Activation Blunts Insulin Delivery to Skeletal Muscle to Cause Insulin Resistance in Mice

    Science.gov (United States)

    Tanigaki, Keiji; Chambliss, Ken L.; Yuhanna, Ivan S.; Sacharidou, Anastasia; Ahmed, Mohamed; Atochin, Dmitriy N.; Huang, Paul L.

    2016-01-01

    Modest elevations in C-reactive protein (CRP) are associated with type 2 diabetes. We previously revealed in mice that increased CRP causes insulin resistance and mice globally deficient in the CRP receptor Fcγ receptor IIB (FcγRIIB) were protected from the disorder. FcγRIIB is expressed in numerous cell types including endothelium and B lymphocytes. Here we investigated how endothelial FcγRIIB influences glucose homeostasis, using mice with elevated CRP expressing or lacking endothelial FcγRIIB. Whereas increased CRP caused insulin resistance in mice expressing endothelial FcγRIIB, mice deficient in the endothelial receptor were protected. The insulin resistance with endothelial FcγRIIB activation was due to impaired skeletal muscle glucose uptake caused by attenuated insulin delivery, and it was associated with blunted endothelial nitric oxide synthase (eNOS) activation in skeletal muscle. In culture, CRP suppressed endothelial cell insulin transcytosis via FcγRIIB activation and eNOS antagonism. Furthermore, in knock-in mice harboring constitutively active eNOS, elevated CRP did not invoke insulin resistance. Collectively these findings reveal that by inhibiting eNOS, endothelial FcγRIIB activation by CRP blunts insulin delivery to skeletal muscle to cause insulin resistance. Thus, a series of mechanisms in endothelium that impairs insulin movement has been identified that may contribute to type 2 diabetes pathogenesis. PMID:27207525

  18. Structural basis for pH-insensitive inhibition of immunoglobulin G recycling by an anti-neonatal Fc receptor antibody

    Energy Technology Data Exchange (ETDEWEB)

    Kenniston, Jon A.; Taylor, Brandy M.; Conley, Gregory P.; Cosic, Janja; Kopacz, Kris J.; Lindberg, Allison P.; Comeau, Stephen R.; Atkins, Kateri; Bullen, Jameson; TenHoor, Christopher; Adelman, Burt A.; Sexton, Daniel J.; Edwards, Thomas E.; Nixon, Andrew E. (Beryllium); (Dyax)

    2017-09-06

    The neonatal Fc receptor FcRn plays a critical role in the trafficking of IgGs across tissue barriers and in retaining high circulating concentrations of both IgG and albumin. Although generally beneficial from an immunological perspective in maintaining IgG populations, FcRn can contribute to the pathogenesis of autoimmune disorders when an abnormal immune response targets normal biological components. We previously described a monoclonal antibody (DX-2507) that binds to FcRn with high affinity at both neutral and acidic pH, prevents the simultaneous binding of IgG, and reduces circulating IgG levels in preclinical animal models. Here, we report a 2.5 Å resolution X-ray crystal structure of an FcRn–DX-2507 Fab complex, revealing a nearly complete overlap of the IgG–Fc binding site in FcRn by complementarity-determining regions in DX-2507. This overlap explains how DX-2507 blocks IgG binding to FcRn and thereby shortens IgG half-life by preventing IgGs from recycling back into circulation. Moreover, the complex structure explains how the DX-2507 interaction is pH-insensitive unlike normal Fc interactions and how serum albumin levels are unaffected by DX-2507 binding. These structural studies could inform antibody-based therapeutic approaches for limiting the effects of IgG-mediated autoimmune disease.

  19. High Affinity IgE-Fc Receptor alpha and gamma Subunit Interactions

    International Nuclear Information System (INIS)

    Rashid, A.; Housden, J. E. M.; Sabban, S.; Helm, B.

    2014-01-01

    Objective: To explore the relationships between the subunits (alpha, beta and gamma) of the high affinity IgE receptor (Fc and RI) and its ability to mediate transmembrane signaling. Study Design: Experimental study. Place and Duration of Study: Department of Molecular Biology and Biotechnology, University of Sheffield, UK, from 2008 to 2009. Methodology: The approach employed was to create a chimera (human alpha-gamma-gamma) using the extracellular (EC) domain of the human high affinity IgE receptor. The alpha subunit (huFc and RIalpha) of IgE receptor was spliced onto the rodent gamma TM and cytoplasmic domain (CD). This was transfected into the Rat Basophilic Leukemia cell line in order to assess the possibility of selectively activating cells transfected with this single pass construct for antigen induced mediator release. Results: The RBLs cell lines transfected with the huFc and RIalpha/gamma/gamma cDNA constructs were assessed for the cell surface expression of the huFc and RIalpha subunit and the response to the antigenic stimulus by looking for degranulation and intracellular Ca2+ mobilisation. The results obtained showed the absence of huFc and RIalpha subunit expression on the surface of transfected cells as seen by flowcytometric studies, beta-hexosaminidase assays and intracellular calcium mobilisation studies. Conclusion: In the present study the grounds for non-expression of huFc and RIalpha/gamma/gamma cDNA remains elusive but may be due to the fact that the human-rodent chimeric receptors are assembled differently than the endogenous rodent receptors as seen in study in which COS 7 cells were transfected with human/rat chimeric complexes. (author)

  20. Fc engineering of anti-Nectin-2 antibody improved thrombocytopenic adverse event in monkey.

    Directory of Open Access Journals (Sweden)

    Tsutomu Oshima

    Full Text Available Nectin-2 is a transmembrane glycoprotein which is involved in the process of Ca2+-independent cell-cell adhesion. In our previous study, we have demonstrated that Nectin-2 is over-expressed in breast and ovarian cancer tissues by using gene expression analysis and immunohistochemistry. Furthermore, we discovered multiple anti-Nectin-2 fully human monoclonal antibodies which inhibited tumor growth in in vivo subcutaneous xenograft models with antibody-dependent cellular cytotoxicity (ADCC as the principal mechanism of action. In this report, we assessed the toxicity of Y-443, a fully human IgG1/kappa anti-Nectin-2 monoclonal antibody exhibiting strong in vitro ADCC and in vivo anti-tumor activity in cynomolgus monkeys (Macaca fascicularis (Cynos. Unexpectedly, upon administration, Y-443 induced strong thrombocytopenia through Nectin-2 expressed on Cyno platelets, presumably followed by phagocytosis in the mononuclear phagocytic system. To mitigate the adverse safety profile, we mutated the Fc region of Y-443 to reduce the Fc binding activity to Fcγ receptor I, which is the primary receptor for phagocytosis on macrophages. Moreover, we further engineered the Fc through defucosylation to maintain ADCC activity. The resultant Fc engineered antibody, termed Y-634, demonstrated diminished thrombocytopenia in Cyno toxicological studies and maintained anti-tumor activity in a mouse xenograft model. These findings suggest that Y-634 may have a therapeutic potential for the treatment of Nectin-2 positive cancers, and moreover, Fc engineering is a potential mitigation strategy to ameliorate safety liabilities in antibody induced thrombocytopenia while maintaining antibody potency.

  1. Unusual ZFC and FC magnetic behavior in thin Co multi-layered structure

    Energy Technology Data Exchange (ETDEWEB)

    Ben-Dor, Oren; Yochelis, Shira [Department of Applied Physics, Center of Nanoscience and Nanotechnology, Hebrew University, Jerusalem 91904 (Israel); Felner, Israel [Racah Institute of Physics, Hebrew University, Jerusalem 91904 (Israel); Paltiel, Yossi [Department of Applied Physics, Center of Nanoscience and Nanotechnology, Hebrew University, Jerusalem 91904 (Israel)

    2017-04-15

    The observation of unusual magnetic phenomena in a Ni -based magnetic memory device ( O. Ben-Dor et al., 2013) encouraged us to conduct a systematic research on Co based multi-layered structure which contains a α-helix L polyalanine (AHPA-L) organic compound. The constant Co thickness is 7 nm and AHPA-L was also replaced by non-chiral 1-Decanethiol organic molecules. Both organic compounds were chemisorbed on gold by a thiol group. The dc magnetic field (H) was applied parallel and perpendicular to the surface layers. The perpendicular direction is the easy magnetization axis and along this orientation only, the zero-field-cooled (ZFC) plots exhibit a pronounced peak around 55–58 K. This peak is suppressed in the second ZFC and field-cooled (FC) runs performed shortly after the virgin ZFC one. Thus, around the peak position ZFC>FC a phenomenon seldom observed. This peak reappears after measuring the same material six months later. This behavior appears in layers with the non-chiral 1-Decanethiol and it is very similar to that obtained in sulfur doped amorphous carbon. The peak origin and the peculiar ZFC>FC case are qualitatively explained. - Highlights: • FC curve crosses ZFC curve in a 7 nm Co and thiol-based organic molecules multi-layered structure. • The ZFC>FC phenomena occurs for H perpendicular along the easy axis. • This phenomenon disappears in the second FC-ZFC run performed shortly after. • The unusual behavior reappears after six months.

  2. Human Endogenous Retrovirus HERV-Fc1 Association with Multiple Sclerosis Susceptibility: A Meta-Analysis

    Science.gov (United States)

    García-Montojo, Marta; Alcina, Antonio; Fedetz, María; Alloza, Iraide; Astobiza, Ianire; Leyva, Laura; Fernández, Oscar; Izquierdo, Guillermo; Antigüedad, Alfredo; Arroyo, Rafael; Álvarez-Lafuente, Roberto; Vandenbroeck, Koen; Matesanz, Fuencisla; Urcelay, Elena

    2014-01-01

    Background Human endogenous retroviruses (HERVs) are repetitive sequences derived from ancestral germ-line infections by exogenous retroviruses and different HERV families have been integrated in the genome. HERV-Fc1 in chromosome X has been previously associated with multiple sclerosis (MS) in Northern European populations. Additionally, HERV-Fc1 RNA levels of expression have been found increased in plasma of MS patients with active disease. Considering the North-South latitude gradient in MS prevalence, we aimed to evaluate the role of HERV-Fc1on MS risk in three independent Spanish cohorts. Methods A single nucleotide polymorphism near HERV-Fc1, rs391745, was genotyped by Taqman chemistry in a total of 2473 MS patients and 3031 ethnically matched controls, consecutively recruited from: Northern (569 patients and 980 controls), Central (883 patients and 692 controls) and Southern (1021 patients and 1359 controls) Spain. Our results were pooled in a meta-analysis with previously published data. Results Significant associations of the HERV-Fc1 polymorphism with MS were observed in two Spanish cohorts and the combined meta-analysis with previous data yielded a significant association [rs391745 C-allele carriers: pM-H = 0.0005; ORM-H (95% CI) = 1.27 (1.11–1.45)]. Concordantly to previous findings, when the analysis was restricted to relapsing remitting and secondary progressive MS samples, a slight enhancement in the strength of the association was observed [pM-H = 0.0003, ORM-H (95% CI) = 1.32 (1.14–1.53)]. Conclusion Association of the HERV-Fc1 polymorphism rs391745 with bout-onset MS susceptibility was confirmed in Southern European cohorts. PMID:24594754

  3. Imaging of injured and atherosclerotic arteries in mice using fluorescence-labeled glycoprotein VI-Fc

    Energy Technology Data Exchange (ETDEWEB)

    Bigalke, Boris, E-mail: boris.bigalke@med.uni-tuebingen.de [Medizinische Klinik III, Kardiologie und Kreislauferkrankungen, Eberhard-Karls-Universitaet Tuebingen (Germany); Division of Imaging Sciences, St Thomas' Hospital, King' s College London (United Kingdom); Pohlmeyer, Ilka; Schoenberger, Tanja [Medizinische Klinik III, Kardiologie und Kreislauferkrankungen, Eberhard-Karls-Universitaet Tuebingen (Germany); Griessinger, Christoph M. [Labor fuer Praeklinische Bildgebung und Bildgebungstechnologie der Werner-Siemens-Stiftung, Radiologische Klinik, Eberhard-Karls-Universitaet Tuebingen (Germany); Ungerer, Martin [Corimmun GmbH, Martinsried (Germany); Botnar, Rene M. [Division of Imaging Sciences, St Thomas' Hospital, King' s College London (United Kingdom); Pichler, Bernd J. [Labor fuer Praeklinische Bildgebung und Bildgebungstechnologie der Werner-Siemens-Stiftung, Radiologische Klinik, Eberhard-Karls-Universitaet Tuebingen (Germany); Gawaz, Meinrad [Medizinische Klinik III, Kardiologie und Kreislauferkrankungen, Eberhard-Karls-Universitaet Tuebingen (Germany)

    2011-08-15

    Purpose: To assess endothelial injury and repair using fluorescence-labeled glycoprotein VI (GPVI)-Fc in a murine model. Materials and methods: Three 4-week-old male ApoE-deficient (ApoE{sup -/-})-mice were fed with a 1.25% cholesterol diet over 16 weeks and compared to three wild type (WT) C57BL/6J-mice in a wire-induced vascular injury model. Another group of WT mice (n = 10) were mechanically injured by carotid ligation. Fluorescence-labeled GPVI-Fc (150 {mu}g/mouse) was administered and assessed by optical imaging 24 h after injury and compared to another group (n = 3) which was injected two days after injury and sacrificed another day later. Results: After denudation, all injured carotids of WT mice showed a higher mean fluorescence signal than the corresponding intact carotids of the same animals (48.4 {+-} 18.9 vs. 10.4 {+-} 1.0; P = 0.028). Injection of unlabeled GPVI-Fc 20 h and 3 h before injecting GPVI-Fc-FITC significantly reduced the fluorescence signal in injured carotids to 14.6 {+-} 4.6, while intact carotids showed a signal of 9.2 {+-} 1.1; P = 0.046. Ligation injury resulted with an increased GPVI-Fc-binding to injured carotids compared to intact carotids (31.53 {+-} 6.18 vs. 16.48 {+-} 5.15; P = 0.039). Three days after injury and 24 h after GPVI-Fc-FITC injection, differences between intact and injured carotids have vanished (12.51 {+-} 2.76 vs. 14.76 {+-} 1.59; P = 0.519). Conclusions: A GPVI-based plaque imaging system could help to identify vascular lesions and to take a precautionary measure as necessary.

  4. Imaging of injured and atherosclerotic arteries in mice using fluorescence-labeled glycoprotein VI-Fc

    International Nuclear Information System (INIS)

    Bigalke, Boris; Pohlmeyer, Ilka; Schoenberger, Tanja; Griessinger, Christoph M.; Ungerer, Martin; Botnar, Rene M.; Pichler, Bernd J.; Gawaz, Meinrad

    2011-01-01

    Purpose: To assess endothelial injury and repair using fluorescence-labeled glycoprotein VI (GPVI)-Fc in a murine model. Materials and methods: Three 4-week-old male ApoE-deficient (ApoE -/- )-mice were fed with a 1.25% cholesterol diet over 16 weeks and compared to three wild type (WT) C57BL/6J-mice in a wire-induced vascular injury model. Another group of WT mice (n = 10) were mechanically injured by carotid ligation. Fluorescence-labeled GPVI-Fc (150 μg/mouse) was administered and assessed by optical imaging 24 h after injury and compared to another group (n = 3) which was injected two days after injury and sacrificed another day later. Results: After denudation, all injured carotids of WT mice showed a higher mean fluorescence signal than the corresponding intact carotids of the same animals (48.4 ± 18.9 vs. 10.4 ± 1.0; P = 0.028). Injection of unlabeled GPVI-Fc 20 h and 3 h before injecting GPVI-Fc-FITC significantly reduced the fluorescence signal in injured carotids to 14.6 ± 4.6, while intact carotids showed a signal of 9.2 ± 1.1; P = 0.046. Ligation injury resulted with an increased GPVI-Fc-binding to injured carotids compared to intact carotids (31.53 ± 6.18 vs. 16.48 ± 5.15; P = 0.039). Three days after injury and 24 h after GPVI-Fc-FITC injection, differences between intact and injured carotids have vanished (12.51 ± 2.76 vs. 14.76 ± 1.59; P = 0.519). Conclusions: A GPVI-based plaque imaging system could help to identify vascular lesions and to take a precautionary measure as necessary.

  5. Fcγ1 fragment of IgG1 as a powerful affinity tag in recombinant Fc-fusion proteins: immunological, biochemical and therapeutic properties.

    Science.gov (United States)

    Soleimanpour, Saman; Hassannia, Tahereh; Motiee, Mahdieh; Amini, Abbas Ali; Rezaee, S A R

    2017-05-01

    Affinity tags are vital tools for the production of high-throughput recombinant proteins. Several affinity tags, such as the hexahistidine tag, maltose-binding protein, streptavidin-binding peptide tag, calmodulin-binding peptide, c-Myc tag, glutathione S-transferase and FLAG tag, have been introduced for recombinant protein production. The fragment crystallizable (Fc) domain of the IgG1 antibody is one of the useful affinity tags that can facilitate detection, purification and localization of proteins and can improve the immunogenicity, modulatory effects, physicochemical and pharmaceutical properties of proteins. Fcγ recombinant forms a group of recombinant proteins called Fc-fusion proteins (FFPs). FFPs are widely used in drug discovery, drug delivery, vaccine design and experimental research on receptor-ligand interactions. These fusion proteins have become successful alternatives to monoclonal antibodies for drug developments. In this review, the physicochemical, biochemical, immunological, pharmaceutical and therapeutic properties of recombinant FFPs were discussed as a new generation of bioengineering strategies.

  6. Ebolavirus Glycoprotein Fc Fusion Protein Protects Guinea Pigs against Lethal Challenge

    Science.gov (United States)

    Konduru, Krishnamurthy; Shurtleff, Amy C.; Bradfute, Steven B.; Nakamura, Siham; Bavari, Sina; Kaplan, Gerardo

    2016-01-01

    Ebola virus (EBOV), a member of the Filoviridae that can cause severe hemorrhagic fever in humans and nonhuman primates, poses a significant threat to the public health. Currently, there are no licensed vaccines or therapeutics to prevent and treat EBOV infection. Several vaccines based on the EBOV glycoprotein (GP) are under development, including vectored, virus-like particles, and protein-based subunit vaccines. We previously demonstrated that a subunit vaccine containing the extracellular domain of the Ebola ebolavirus (EBOV) GP fused to the Fc fragment of human IgG1 (EBOVgp-Fc) protected mice against EBOV lethal challenge. Here, we show that the EBOVgp-Fc vaccine formulated with QS-21, alum, or polyinosinic-polycytidylic acid-poly-L-lysine carboxymethylcellulose (poly-ICLC) adjuvants induced strong humoral immune responses in guinea pigs. The vaccinated animals developed anti-GP total antibody titers of approximately 105−106 and neutralizing antibody titers of approximately 103 as assessed by a BSL-2 neutralization assay based on vesicular stomatitis virus (VSV) pseudotypes. The poly-ICLC formulated EBOVgp-Fc vaccine protected all the guinea pigs against EBOV lethal challenge performed under BSL-4 conditions whereas the same vaccine formulated with QS-21 or alum only induced partial protection. Vaccination with a mucin-deleted EBOVgp-Fc construct formulated with QS-21 adjuvant did not have a significant effect in anti-GP antibody levels and protection against EBOV lethal challenge compared to the full-length GP construct. The bulk of the humoral response induced by the EBOVgp-Fc vaccine was directed against epitopes outside the EBOV mucin region. Our findings indicate that different adjuvants can eliciting varying levels of protection against lethal EBOV challenge in guinea pigs vaccinated with EBOVgp-Fc, and suggest that levels of total anti-GP antibodies elicit by protein-based GP subunit vaccines do not correlate with protection. Our data further support

  7. Relationship between Fc receptors and Ia alloantigens: analysis with a sensitive radioimmunoassay

    International Nuclear Information System (INIS)

    Rieber, E.P.; Wernet, P.

    1977-01-01

    This paper describes the successful use of 125 I-labeled lgG aggregate to detect la-type alloantibodies in pregnancy sera. The blockade of aggregate uptake of a variety of normal mononuclear and leukemic cell types by anti-Ia alloantibodies is analyzed. Fc receptors and la alloantigens are clearly two distinct molecular entities. The association between Fc receptors and Ia alloantigens on a quantitative level seems to depend on a ligand-binding mechanism to control their interaction rather than the presence of a topographical molecular tandem arrangement. (Auth.)

  8. Ebolavirus Glycoprotein Fc Fusion Protein Protects Guinea Pigs against Lethal Challenge.

    Science.gov (United States)

    Konduru, Krishnamurthy; Shurtleff, Amy C; Bradfute, Steven B; Nakamura, Siham; Bavari, Sina; Kaplan, Gerardo

    2016-01-01

    Ebola virus (EBOV), a member of the Filoviridae that can cause severe hemorrhagic fever in humans and nonhuman primates, poses a significant threat to the public health. Currently, there are no licensed vaccines or therapeutics to prevent and treat EBOV infection. Several vaccines based on the EBOV glycoprotein (GP) are under development, including vectored, virus-like particles, and protein-based subunit vaccines. We previously demonstrated that a subunit vaccine containing the extracellular domain of the Ebola ebolavirus (EBOV) GP fused to the Fc fragment of human IgG1 (EBOVgp-Fc) protected mice against EBOV lethal challenge. Here, we show that the EBOVgp-Fc vaccine formulated with QS-21, alum, or polyinosinic-polycytidylic acid-poly-L-lysine carboxymethylcellulose (poly-ICLC) adjuvants induced strong humoral immune responses in guinea pigs. The vaccinated animals developed anti-GP total antibody titers of approximately 105-106 and neutralizing antibody titers of approximately 103 as assessed by a BSL-2 neutralization assay based on vesicular stomatitis virus (VSV) pseudotypes. The poly-ICLC formulated EBOVgp-Fc vaccine protected all the guinea pigs against EBOV lethal challenge performed under BSL-4 conditions whereas the same vaccine formulated with QS-21 or alum only induced partial protection. Vaccination with a mucin-deleted EBOVgp-Fc construct formulated with QS-21 adjuvant did not have a significant effect in anti-GP antibody levels and protection against EBOV lethal challenge compared to the full-length GP construct. The bulk of the humoral response induced by the EBOVgp-Fc vaccine was directed against epitopes outside the EBOV mucin region. Our findings indicate that different adjuvants can eliciting varying levels of protection against lethal EBOV challenge in guinea pigs vaccinated with EBOVgp-Fc, and suggest that levels of total anti-GP antibodies elicit by protein-based GP subunit vaccines do not correlate with protection. Our data further support

  9. Ebolavirus Glycoprotein Fc Fusion Protein Protects Guinea Pigs against Lethal Challenge.

    Directory of Open Access Journals (Sweden)

    Krishnamurthy Konduru

    Full Text Available Ebola virus (EBOV, a member of the Filoviridae that can cause severe hemorrhagic fever in humans and nonhuman primates, poses a significant threat to the public health. Currently, there are no licensed vaccines or therapeutics to prevent and treat EBOV infection. Several vaccines based on the EBOV glycoprotein (GP are under development, including vectored, virus-like particles, and protein-based subunit vaccines. We previously demonstrated that a subunit vaccine containing the extracellular domain of the Ebola ebolavirus (EBOV GP fused to the Fc fragment of human IgG1 (EBOVgp-Fc protected mice against EBOV lethal challenge. Here, we show that the EBOVgp-Fc vaccine formulated with QS-21, alum, or polyinosinic-polycytidylic acid-poly-L-lysine carboxymethylcellulose (poly-ICLC adjuvants induced strong humoral immune responses in guinea pigs. The vaccinated animals developed anti-GP total antibody titers of approximately 105-106 and neutralizing antibody titers of approximately 103 as assessed by a BSL-2 neutralization assay based on vesicular stomatitis virus (VSV pseudotypes. The poly-ICLC formulated EBOVgp-Fc vaccine protected all the guinea pigs against EBOV lethal challenge performed under BSL-4 conditions whereas the same vaccine formulated with QS-21 or alum only induced partial protection. Vaccination with a mucin-deleted EBOVgp-Fc construct formulated with QS-21 adjuvant did not have a significant effect in anti-GP antibody levels and protection against EBOV lethal challenge compared to the full-length GP construct. The bulk of the humoral response induced by the EBOVgp-Fc vaccine was directed against epitopes outside the EBOV mucin region. Our findings indicate that different adjuvants can eliciting varying levels of protection against lethal EBOV challenge in guinea pigs vaccinated with EBOVgp-Fc, and suggest that levels of total anti-GP antibodies elicit by protein-based GP subunit vaccines do not correlate with protection. Our data

  10. Quantitative glycan profiling of normal human plasma derived immunoglobulin and its fragments Fab and Fc.

    Science.gov (United States)

    Anumula, Kalyan Rao

    2012-08-31

    Typical clinical grade human IgG (intravenous immunoglobulin, IVIG), used for carbohydrate analysis, is derived from thousands of healthy donors. Quantitative high-resolution glycan profiles of IgG and its Fc-Fab fragments are presented here. Glycan profiles were established following digestions with Fc specific endoglycosidase S and generic PNGase F under denaturing and non-denaturing (native) conditions. The native PNGase F glycan profile of IgG was similar (but not identical) to that of Endo S. Endo S profiles did not contain the glycans with bisecting GlcNAc. PNGase F glycan profiles were the same for Fc fragments that were isolated from pepsin and Ide S protease digests. Both isolated Fab fragments and the previously deglycosylated IVIG (native conditions) yielded the same glycan profile. Glycan profiles were established using high resolution HPLC with 2-aminobenzoic acid (2AA) labeling. An accurate determination of sialylation levels can be made by this method. Carbohydrate content in Fc and Fab was determined using an internal standard and corrected for both protein and glycan recoveries. Fab portion contained about 14% of the total carbohydrate which translates to 2.3 sugar chains per mol in IVIG where 2 chains are located in the CH2 domain of the Fc. Fc glycans consisted of neutral (N) 84.5%; mono-sialylated (S1) 15% and di-sialylated (S2) 0.5%. In contrast, Fab contained N, 21%; S1, 43% and S2, 36%. The distribution of bisecting N-acetylglucosamine and fucose was found to be very different in various glycans (N, S1 and S2) found in Fab and Fc. Total IgG glycan profile (Fab plus Fc) contained N, 78.5%; S1, 17% and S2, 4.5%. Percent distribution of glycans G0, G1 and G2 (with 0, 1 and 2 two galactoses) was 26, 49 and 25 respectively within the 78% of the neutral glycans. Glycan profiles were nearly the same for various clinical grade IVIG preparations from various manufacturers. A fast HPLC profiling method was developed for the separation and quantitation

  11. FC Lahden jalkapalloilijoiden tiedon lisääminen vammojen ennaltaehkäisystä

    OpenAIRE

    Lagerblom, Jessica

    2011-01-01

    Opinnäytetyö tehtiin yhteistyössä jalkapallon Miesten Ykkösessä pelaava FC Lahden kanssa. Tarve työlle syntyi valmennuksen huolesta pelaajien terveenä pysymistä kohtaan. Pelaajien tiedot vammojen ennaltaehkäisystä ja motivaatio itsestä huolehtimiseen ovat osoittautuneet riittämättömiksi pelaajien vaatimustasoon nähden. Tästä ovat osoituksena lukuisat uusiutuneet jalkapallovammat edellisinä kausina. Työn tarkoituksena oli parantaa FC Lahden jalkapalloilijoiden tietämystä jalkapallovammojen...

  12. Modeling on bubbly to churn flow pattern transition for vertical upward flows in narrow rectangular channel

    International Nuclear Information System (INIS)

    Wang Yanlin; Chen Bingde; Huang Yanping; Wang Junfeng

    2011-01-01

    A theoretical model was developed to predict the bubbly to churn flow pattern transition for vertical upward flows in narrow rectangular channel. The model was developed based on the imbalance theory of Helmholtz and some reasonable assumptions. The maximum ideal bubble in narrow rectangular channel and the thermal hydraulics boundary condition leading to bubbly flow to churn flow pattern transition was calculated. The model was validated by experimental data from previous researches. Comparison between predicted result and experimental result shows a reasonable good agreement. (author)

  13. Method of online cleanliness control for upward-facing transport mirrors in integration test bed

    International Nuclear Information System (INIS)

    Zhao Longbiao; Qin Lang; Zhou Guorui; Ye Yayun; Zhang Chuanchao; Miao Xinxiang; Wang Hongbin; Yuan Xiaodong; Wang Xiaohong; Cheng Xiaofeng

    2013-01-01

    An online cleanliness control method based on the online monitoring system was developed for controlling the particle pollution and damage of upward-facing transport mirrors in the integration test bed. By building up gas knife system, the online cleanliness processing was effectively achieved for the particle pollution on the mirror surface. By using the gas screen, the cleanliness of the mirror surface was effectively online maintained. The image processing system was applied to assessing the effect of online cleanliness processing. The experimental results indicate that the particle pollution was reduced by the gas knife and the gas screen was useful to avoid the settlement of particle pollution. (authors)

  14. Experimental Investigation of the Hot Water Layer Effect on Upward Flow Open Pool Reactor Operability

    International Nuclear Information System (INIS)

    Abou Elmaaty, T.

    2014-01-01

    The open pool reactor offers a high degree of reliability in the handling and manoeuvring, the replacement of reactor internal components and the suing of vertical irradiation channels. The protection of both the operators and the reactor hall environment against radiation hazards is considered a matter of interest. So, a hot water layer is implemented above many of the research reactors main pool, especially those whose flow direction is upward flow. An experimental work was carried out to ensure the operability of the upward flow open pool research reactor with / without the hot water layer. The performed experiment showed that, the hot water layer is produced an inverse buoyant force make the water to diffuse downward against the ordinary natural circulation from the reactor core. An upward flow - open pool research reactor (with a power greater than 20 M watt) could not wok without a hot water layer. The high temperature of the hot water layer surface could release a considerable amount of water vapour into the reactor hall, so a heat and mass transfer model is built based on the measured hot water layer surface temperature to calculate the amount of released water vapour during the reactor operating period. The effects of many parameters like the ambient air temperature, the reactor hall relative humidity and the speed of the pushed air layer above the top pool end on the evaporation rate is studied. The current study showed that, the hot water layer system is considered an efficient shielding system against Gamma radiation for open pool upward flow reactor and that system should be operated before the reactor start up by a suitable period of time. While, the heat and mass transfer model results showed that, the amount of the released water vapour is increased as a result of both the increase in hot water layer surface temperature and the increase in air layer speed. As the increase in hot water layer surface temperature could produce a good operability

  15. Experimental Investigation of the Hot Water Layer Effect on Upward Flow Open Pool Reactor Operability

    International Nuclear Information System (INIS)

    Abou Elmaaty, T.

    2015-01-01

    The open pool reactor offers a high degree of reliability in the handling and manoeuvring, the replacement of reactor internal components and the swing of vertical irradiation channels. The protection of both the operators and the reactor hall environment against radiation hazards is considered a matter of interest. So, a hot water layer implemented above many of the research reactors main pool, especially those whose flow direction is upward flow. An experimental work was carried out to ensure the operability of the upward flow open pool research reactor with / without the hot water layer. The performed experiment showed that, the hot water layer produced an inverse buoyant force making the water to diffuse downward against the ordinary natural circulation from the reactor core. An upward flow-open pool research reactor (with a power greater than 20 Mw) could not wok without a hot water layer. The high temperature of the hot water layer surface could release a considerable amount of water vapour into the reactor hall, so a heat and mass transfer model is built based on the measured hot water layer surface temperature to calculate the amount of released water vapour during the reactor operating period. The effects of many parameters like the ambient air temperature, the reactor hall relative humidity and the speed of the pushed air layer above the top pool end on the evaporation rate is studied. The current study showed that, the hot water layer system is considered an efficient shielding system against gamma radiation for open pool upward flow reactor and that system should be operated before the reactor start up by a suitable period of time. While, the heat and mass transfer model results showed that, the amount of the released water vapour is increased as a result of both the increase in hot water layer surface temperature and the increase in air layer speed. As the increase in hot water layer surface temperature could produce a good operability conditions from

  16. Correlating the Impact of Well-Defined Oligosaccharide Structures on Physical Stability Profiles of IgG1-Fc Glycoforms.

    Science.gov (United States)

    More, Apurva S; Toprani, Vishal M; Okbazghi, Solomon Z; Kim, Jae H; Joshi, Sangeeta B; Middaugh, C Russell; Tolbert, Thomas J; Volkin, David B

    2016-02-01

    As part of a series of articles in this special issue describing 4 well-defined IgG1-Fc glycoforms as a model system for biosimilarity analysis (high mannose-Fc, Man5-Fc, GlcNAc-Fc and N297Q-Fc aglycosylated), the focus of this work is comparisons of their physical properties. A trend of decreasing apparent solubility (thermodynamic activity) by polyethylene glycol precipitation (pH 4.5, 6.0) and lower conformational stability by differential scanning calorimetry (pH 4.5) was observed with reducing size of the N297-linked oligosaccharide structures. Using multiple high-throughput biophysical techniques, the physical stability of the Fc glycoproteins was then measured in 2 formulations (NaCl and sucrose) across a wide range of temperatures (10°C-90°C) and pH (4.0-7.5) conditions. The data sets were used to construct 3-index empirical phase diagrams and radar charts to visualize the regions of protein structural stability. Each glycoform showed improved stability in the sucrose (vs. salt) formulation. The HM-Fc and Man5-Fc displayed the highest relative stability, followed by GlcNAc-Fc, with N297Q-Fc being the least stable. Thus, the overall physical stability profiles of the 4 IgG1-Fc glycoforms also show a correlation with oligosaccharide structure. These data sets are used to develop a mathematical model for biosimilarity analysis (as described in a companion article by Kim et al. in this issue). Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  17. Bubble Clouds and their Transport within the Surf Zone as Measured with a Distributed Array of Upward-Looking Sonars

    National Research Council Canada - National Science Library

    Dahl, Peter

    2000-01-01

    ... in the surf zone and the effects of these bubbles on acoustic propagation. This paper discusses data gathered by the Applied Physics Laboratory, University of Washington, using a set of four upward-looking sonars (frequency 240 kHz...

  18. Methane and carbon dioxide fluxes over a lake: comparison between eddy covariance, floating chambers and boundary layer method

    Directory of Open Access Journals (Sweden)

    K.-M. Erkkilä

    2018-01-01

    Full Text Available Freshwaters bring a notable contribution to the global carbon budget by emitting both carbon dioxide (CO2 and methane (CH4 to the atmosphere. Global estimates of freshwater emissions traditionally use a wind-speed-based gas transfer velocity, kCC (introduced by Cole and Caraco, 1998, for calculating diffusive flux with the boundary layer method (BLM. We compared CH4 and CO2 fluxes from BLM with kCC and two other gas transfer velocities (kTE and kHE, which include the effects of water-side cooling to the gas transfer besides shear-induced turbulence, with simultaneous eddy covariance (EC and floating chamber (FC fluxes during a 16-day measurement campaign in September 2014 at Lake Kuivajärvi in Finland. The measurements included both lake stratification and water column mixing periods. Results show that BLM fluxes were mainly lower than EC, with the more recent model kTE giving the best fit with EC fluxes, whereas FC measurements resulted in higher fluxes than simultaneous EC measurements. We highly recommend using up-to-date gas transfer models, instead of kCC, for better flux estimates. BLM CO2 flux measurements had clear differences between daytime and night-time fluxes with all gas transfer models during both stratified and mixing periods, whereas EC measurements did not show a diurnal behaviour in CO2 flux. CH4 flux had higher values in daytime than night-time during lake mixing period according to EC measurements, with highest fluxes detected just before sunset. In addition, we found clear differences in daytime and night-time concentration difference between the air and surface water for both CH4 and CO2. This might lead to biased flux estimates, if only daytime values are used in BLM upscaling and flux measurements in general. FC measurements did not detect spatial variation in either CH4 or CO2 flux over Lake Kuivajärvi. EC measurements, on the other hand, did not show any spatial variation in CH4 fluxes but did show a clear difference

  19. Activatory and Inhibitory Fcγ Receptors Augment Rituximab-mediated Internalization of CD20 Independent of Signaling via the Cytoplasmic Domain*

    Science.gov (United States)

    Vaughan, Andrew T.; Chan, Claude H. T.; Klein, Christian; Glennie, Martin J.; Beers, Stephen A.; Cragg, Mark S.

    2015-01-01

    Type I anti-CD20 mAb such as rituximab and ofatumumab engage with the inhibitory FcγR, FcγRIIb on the surface of B cells, resulting in immunoreceptor tyrosine-based inhibitory motif (ITIM) phosphorylation. Internalization of the CD20·mAb·FcγRIIb complex follows, the rate of which correlates with FcγRIIb expression. In contrast, although type II anti-CD20 mAb such as tositumomab and obinutuzumab also interact with and activate FcγRIIb, this interaction fails to augment the rate of CD20·mAb internalization, raising the question of whether ITIM phosphorylation plays any role in this process. We have assessed the molecular requirements for the internalization process and demonstrate that in contrast to internalization of IgG immune complexes, FcγRIIb-augmented internalization of rituximab-ligated CD20 occurs independently of the FcγRIIb ITIM, indicating that signaling downstream of FcγRIIb is not required. In transfected cells, activatory FcγRI, FcγRIIa, and FcγRIIIa augmented internalization of rituximab-ligated CD20 in a similar manner. However, FcγRIIa mediated a slower rate of internalization than cells expressing equivalent levels of the highly homologous FcγRIIb. The difference was maintained in cells expressing FcγRIIa and FcγRIIb lacking cytoplasmic domains and in which the transmembrane domains had been exchanged. This difference may be due to increased degradation of FcγRIIa, which traffics to lysosomes independently of rituximab. We conclude that the cytoplasmic domain of FcγR is not required for promoting internalization of rituximab-ligated CD20. Instead, we propose that FcγR provides a structural role in augmenting endocytosis that differs from that employed during the endocytosis of immune complexes. PMID:25568316

  20. Emerging psychopathology moderates upward social mobility: The intergenerational (dis)continuity of socioeconomic status.

    Science.gov (United States)

    Véronneau, Marie-Hélène; Serbin, Lisa A; Stack, Dale M; Ledingham, Jane; Schwartzman, Alex E

    2015-11-01

    Socioeconomic status (SES) is relatively stable across generations, but social policies may create opportunities for upward social mobility among disadvantaged populations during periods of economic growth. With respect to expanded educational opportunities that occurred in Québec (Canada) during the 1960s, we hypothesized that children's social and academic competence would promote upward mobility, whereas aggression and social withdrawal would have the opposite effect. Out of 4,109 children attending low-SES schools in 1976-1978, a representative subsample of 503 participants were followed until midadulthood. Path analyses revealed that parents' SES predicted offspring's SES through associations with offspring's likeability, academic competence, and educational attainment. Interaction effects revealed individual risk factors that moderated children's ability to take advantage of intrafamilial or extrafamilial opportunities that could enhance their educational attainment. Highly aggressive participants and those presenting low academic achievement were unable to gain advantage from having highly educated parents. They reached lower educational attainment than their less aggressive or higher achieving peers who came from a similarly advantaged family background. Growing up with parents occupying low-prestige jobs put withdrawn boys and outgoing girls at risk for low educational attainment. In conclusion, social policies can raise SES across generations, with great benefits for the most disadvantaged segments of the population. However, children presenting with emerging psychopathology or academic weaknesses do not benefit from these policies as much as others, and should receive additional, targeted services.

  1. Influence of Mining Thickness on the Rationality of Upward Mining in Coal Seam Group

    Directory of Open Access Journals (Sweden)

    Y. Li

    2016-04-01

    Full Text Available This study aimed to determine the influence of mining thickness on the rationality of upward mining in coal seam group. Numerical simulation and theoretical analysis were performed to investigate the influence of the mining thicknesses of initial mining seam on the destruction and pressure relief effect of the upper coal seam in a high-gas coal seam group. The mechanical model of the roof failure based on the mining thickness was established by assuming that the gob formed after adjacent panels have fully been caved is the infinite plane. On the basis of this model, an equation was derived to calculate the roof failure height of the panel. Considering the geological conditions of No. 9 and No. 12 coal seams of Zhaogezhuang Coal Mine, economic effectiveness, and proposed techniques, we concluded that the top layer (4 m of the No. 12 coal seam should be mined first. The top layer of the No. 9 coal seam should be subsequently mined. The topcaving technique was applied to the exploitation of the lower layer of the No. 12 coal seam. Practically monitored data revealed that the deformation and failure of the No. 2699 panel roadway was small and controllable, the amount of gas emission was reduced significantly, and the effect of upward mining was active. The results of this study provide theory basics for mine designing, and it is the provision of a reference for safe and efficient coal exploitation under similar conditions.

  2. Underlying mechanism of precursory activity from analysis of upward earthquake migration

    Directory of Open Access Journals (Sweden)

    O. A. Molchanov

    2011-01-01

    Full Text Available In this paper we analyse the upward earthquake hypocentral migration in the ten known subduction zones and discuss a possible mechanism of such migration. The total time of the migration appears to range from 2.5 to 10 years. It leads to the estimation of the average velocity Vz~ 60−300 km yr−1. It probably corresponds to the movement of the forcing agent like stress or deformation wave from depths of the upper mantle (600–700 km to the level of the lithosphere with subsequent initiation of fluid migration inside the crust to trigger shallow earthquakes. Averaged over all zones upward migration travel time is about 5 years (< Vz > ≈120 km yr−1 that coincides approximately with the period of characteristic temperature variation (El Nino and crustal seismic periodicity in the Pacific region. These findings are helpful for the study of the seismic precursors and analysis of earthquake triggering.

  3. Chimeric immunoglobulin E reactive with tumor-associated antigen activates human Fc epsilon RI bearing cells

    NARCIS (Netherlands)

    Luiten, R. M.; Warnaar, S. O.; Schuurman, J.; Pasmans, S. G.; Latour, S.; Daëron, M.; Fleuren, G. J.; Litvinov, S. V.

    1997-01-01

    Crosslinking of immunoglobulin E molecules that are bound to the Fc epsilon receptors expressed on mast cells or basophils triggers activation of these cells, resulting in the development of a type I hypersensitivity. Targeting this potent immune reaction towards tumors by using IgE that reacts with

  4. Stabilization and augmentation of circulating AIM in mice by synthesized IgM-Fc.

    Directory of Open Access Journals (Sweden)

    Toshihiro Kai

    Full Text Available Owing to rapid and drastic changes in lifestyle and eating habits in modern society, obesity and obesity-associated diseases are among the most important public health problems. Hence, the development of therapeutic approaches to regulate obesity is strongly desired. In view of previous work showing that apoptosis inhibitor of macrophage (AIM blocks lipid storage in adipocytes, thereby preventing obesity caused by a high-fat diet, we here explored a strategy to augment circulating AIM levels. We synthesized the Fc portion of the soluble human immunoglobulin (IgM heavy chain and found that it formed a pentamer containing IgJ as natural IgM does, and effectively associated with AIM in vitro. When we injected the synthesized Fc intravenously into mice lacking circulating IgM, it associated with endogenous mouse AIM, protecting AIM from renal excretion and preserving the circulating AIM levels. As the synthesized Fc lacked the antigen-recognizing variable region, it provoked no undesired immune response. In addition, a challenge with the Fc-human AIM complex in wild-type mice, which exhibited normal levels of circulating IgM and AIM, successfully maintained the levels of the human AIM in mouse blood. We also observed that the human AIM was effectively incorporated into adipocytes in visceral fat tissue, suggesting its functionality against obesity. Thus, our findings reveal potent strategies to safely increase AIM levels, which could form the basis for developing novel therapies for obesity.

  5. [Eukaryotic Expression and Immunogenic Research of Recombination Ebola Virus Membrane Protein Gp-Fc].

    Science.gov (United States)

    Zhang, Xiaoguang; Yang, Ren; Wang, Jiao; Wang, Xuan; Hou, Mieling; An, Lina; Zhu, Ying; Cao, Yuxi; Zeng, Yi

    2016-01-01

    We used 293 cells to express the recombinant membrane protein of the Ebola virus. Then, the immunogenicity of the recombinant protein was studied by immunized BALB/c mice. According to the codon use frequency of humans, the gene encoding the extracellular domain of the Ebola virus membrane protein was optimized, synthesized, and inserted into the eukaryotic expression plasmid pXG-Fc to construct the human IgG Fc and Ebola GP fusion protein expression plasmid pXG-modGP-Fc. To achieve expression, the fusion protein expression vector was transfected into high-density 293 cells using transient transfection technology. The recombinant protein was purified by protein A affinity chromatography. BALB/c mice were immunized with the purified fusion protein, and serum antibody titers evaluated by an indirect enzyme-linked immunosorbent assay (ELISA). Purification and analyses of the protein revealed that the eukaryotic expression vector could express the recombinant protein GP-Fc effectively, and that the recombinant protein in the supernatant of the cell culture was present as a dimer. After immunization with the purified recombinant protein, a high titer of antigen-specific IgG could be detected in the serum of immunized mice by indirect ELISA, showing that the recombinant protein had good immunogenicity. These data suggest that we obtained a recombinant protein with good immunogenicity. Our study is the basis for development of a vaccine against the Ebola virus and for screening of monoclonal antibodies.

  6. Design of intelligent gateway control system based on AllJoyn and FC-3180

    Directory of Open Access Journals (Sweden)

    Chen Yanzhong

    2017-02-01

    Full Text Available To simplify interconnection of distributed household equipment,this design creates a spontaneous,movable,safe and configurable equipment management system and smart home layout with the open-source software framework AllJoyn,the embedded microprocessor FC-3180,the low power wireless transmission network ZigBee and mobile application platform Android.

  7. Measuring Convective Mass Fluxes Over Tropical Oceans

    Science.gov (United States)

    Raymond, David

    2017-04-01

    Deep convection forms the upward branches of all large-scale circulations in the tropics. Understanding what controls the form and intensity of vertical convective mass fluxes is thus key to understanding tropical weather and climate. These mass fluxes and the corresponding conditions supporting them have been measured by recent field programs (TPARC/TCS08, PREDICT, HS3) in tropical disturbances considered to be possible tropical storm precursors. In reality, this encompasses most strong convection in the tropics. The measurements were made with arrays of dropsondes deployed from high altitude. In some cases Doppler radar provided additional measurements. The results are in some ways surprising. Three factors were found to control the mass flux profiles, the strength of total surface heat fluxes, the column-integrated relative humidity, and the low to mid-tropospheric moist convective instability. The first two act as expected, with larger heat fluxes and higher humidity producing more precipitation and stronger lower tropospheric mass fluxes. However, unexpectedly, smaller (but still positive) convective instability produces more precipitation as well as more bottom-heavy convective mass flux profiles. Furthermore, the column humidity and the convective instability are anti-correlated, at least in the presence of strong convection. On spatial scales of a few hundred kilometers, the virtual temperature structure appears to be in dynamic balance with the pattern of potential vorticity. Since potential vorticity typically evolves on longer time scales than convection, the potential vorticity pattern plus the surface heat fluxes then become the immediate controlling factors for average convective properties. All measurements so far have taken place in regions with relatively flat sea surface temperature (SST) distributions. We are currently seeking funding for a measurement program in the tropical east Pacific, a region that exhibits strong SST gradients and

  8. Turbulent Fogwater Flux Measurements Above A Forest

    Science.gov (United States)

    Burkard, R.; Eugster, W.; Buetzberger, P.; Siegwolf, R.

    Many forest ecosystems in elevated regions receive a significant fraction of their wa- ter and nutrient input by the interception of fogwater. Recently, several studies have demonstrated the suitability of the eddy covariance technique for the direct measure- ment of turbulent liquid water fluxes. Since summer 2001 a fogwater flux measure- ment equipment has been running at a montane site above a mixed forest canopy in Switzerland. The measurement equipment consists of a high-speed size-resolving droplet spectrometer and a three-dimensional ultrasonic anemometer. The chemical composition of the fogwater was determined from samples collected with a modified Caltech active strand collector. The deposition of nutrients by fog (occult deposition) was calculated by multiplying the total fogwater flux (total of measured turbulent and calculated gravitational flux) during each fog event by the ionic concentrations found in the collected fogwater. Several uncertainties still exist as far as the accuracy of the measurements is con- cerned. Although there is no universal statistical approach for testing the quality of the liquid water flux data directly, results of independent data quality checks of the two time series involved in the flux computation and accordingly the two instruments (ultrasonic anemometer and the droplet spectrometer) are presented. Within the measurement period, over 80 fog events with a duration longer than 2.5 hours were analyzed. An enormous physical and chemical heterogeneity among these fog events was found. We assume that some of this heterogeneity is due to the fact that fog or cloud droplets are not conservative entities: the turbulent flux of fog droplets, which can be referred to as the liquid water flux, is affected by phase change processes and coagulation. The measured coexistence of upward fluxes of small fog droplets (di- ameter < 10 µm) with the downward transport of larger droplets indicates the influ- ence of such processes. With the

  9. APC targeting enhances immunogenicity of a novel multistage Fc-fusion tuberculosis vaccine in mice.

    Science.gov (United States)

    Soleimanpour, Saman; Farsiani, Hadi; Mosavat, Arman; Ghazvini, Kiarash; Eydgahi, Mohammad Reza Akbari; Sankian, Mojtaba; Sadeghian, Hamid; Meshkat, Zahra; Rezaee, Seyed Abdolrahim

    2015-12-01

    Numerous studies have demonstrated that targeting immunogens to FcγR on antigen-presenting cells (APCs) can selectively uptake and increase cellular immunity in vitro and in vivo. Therefore, the present study was conducted to evaluate immunogenicity of a novel multistage tuberculosis vaccine, a combination of an early and a dormant immunogenic protein, ESAT6 and HspX, fused to Fcγ2a fragment of mouse IgG2a to target all forms of tuberculosis. Codon-optimized genes consisting of ESAT6, a linker, and HspX fused either to mouse Fcγ2a (ESAT6:HspX:mFcγ2a) or 6× His-tag (ESAT6:HspX:His) were synthesized. The resulting proteins were then produced in Pichia pastoris. The fusion proteins were separately emulsified in dimethyldioctadecylammonium bromide(DDA)-trehalose-6,6-dibehenate(TDB) adjuvant, and their immunogenicity with and without bacille Calmette-Guérin (BCG) was assessed in C57BL/6 mice. Th1, Th2, Th17, and T-reg cytokine patterns were evaluated using the ELISA method. Both multistage vaccines induced very strong IL-12 and IFN-γ secretion from splenic cells; the Fc-tagged subunit vaccine induced a more effective Th1 immune response (IFN-γ, 910 pg/mL, and IL-12, 854 pg/mL) with a very low increase in IL-17 (∼0.1 pg/mL) and IL-4 (37 pg/mL) and a mild increase in TGF-β (543 pg/mL) compared to the BCG or ESAT6:HspX:His primed and boosted groups. The production of IFN-γ to ESAT6:HspX:Fcγ2a was very consistent and showed an increasing trend for IL-12 compared to the BCG or ESAT6:HspX:His primed and boosted groups. Fcγ2a used as a delivery vehicle supported the idea of selective uptake, inducing cross-presentation and forming a proper anti-tuberculosis response in context of Th1/Th2 and Th17/T-reg balances, which is important for protection and prevention of damage.

  10. Conformational destabilization of Immunoglobulin G increases the low pH-binding affinity with the Neonatal Fc Receptor

    DEFF Research Database (Denmark)

    Walters, Benjamin T; Jensen, Pernille Foged; Larraillet, Vincent

    2016-01-01

    Crystallographic evidence suggests that the pH-dependent affinity of IgG molecules for the neonatal Fc receptor (FcRn) receptor primarily arises from salt bridges involving IgG histidine residues, resulting in moderate affinity at mildly acidic conditions. However, this view does not explain the ......H-dependent affinity in IgG-FcRn interactions and exemplify the important and often ignored role of intrinsic conformational dynamics in a protein ligand, to dictate affinity for biologically important receptors.......Crystallographic evidence suggests that the pH-dependent affinity of IgG molecules for the neonatal Fc receptor (FcRn) receptor primarily arises from salt bridges involving IgG histidine residues, resulting in moderate affinity at mildly acidic conditions. However, this view does not explain...... the diversity in affinity found in IgG variants, such as the YTE mutant (M252Y,S254T,T256E), which increases affinity to FcRn by up to 10×. Here we compare hydrogen exchange measurements at pH 7.0 and pH 5.5 with and without FcRn bound with surface plasmon resonance estimates of dissociation constants and Fc...

  11. Evaluation of FcεRl-binding serum IgE in patients with ocular allergic diseases

    Directory of Open Access Journals (Sweden)

    Satoru Matsumoto

    1999-01-01

    Full Text Available We evaluated high-affinity receptor for IgE (FcεRI- binding serum IgE in patients with atopic keratoconjunctivitis (AKC; n=31 and with seasonal allergic conjunctivitis (SAC; n=13 by enzyme-linked immunosorbent assay (ELISA using a recombinant soluble form of the human FcεRIα ectodomain (soluble α. The quantities of FcεRI-binding IgE are compared with those of total IgE measured by a conventional sandwich ELISA. Both of the quantities of FcεRI-binding and total IgE in AKC were significantly larger than those in SAC (P<0.001. In contrast, the proportion of FcεRI- binding IgE (FcεRI-binding IgE/total IgE; % in SAC was significantly larger than that in AKC (P <0.001, although significant reverse correlation was observed between the proportion of FcεRI-binding IgE and total IgE in both AKC and SAC. Significantly, a higher proportion of FcεRI-binding IgE in SAC than that in AKC may reflect the differences in pathologic states of AKC and SAC that are caused by a disparity in immune responses in these diseases.

  12. Prolonged activity of a recombinant factor VIII-Fc fusion protein in hemophilia A mice and dogs

    Science.gov (United States)

    Dumont, Jennifer A.; Liu, Tongyao; Low, Susan C.; Zhang, Xin; Kamphaus, George; Sakorafas, Paul; Fraley, Cara; Drager, Douglas; Reidy, Thomas; McCue, Justin; Franck, Helen W. G.; Merricks, Elizabeth P.; Nichols, Timothy C.; Bitonti, Alan J.; Pierce, Glenn F.

    2012-01-01

    Despite proven benefits, prophylactic treatment for hemophilia A is hampered by the short half-life of factor VIII. A recombinant factor VIII-Fc fusion protein (rFVIIIFc) was constructed to determine the potential for reduced frequency of dosing. rFVIIIFc has an ∼ 2-fold longer half-life than rFVIII in hemophilia A (HemA) mice and dogs. The extension of rFVIIIFc half-life requires interaction of Fc with the neonatal Fc receptor (FcRn). In FcRn knockout mice, the extension of rFVIIIFc half-life is abrogated, and is restored in human FcRn transgenic mice. The Fc fusion has no impact on FVIII-specific activity. rFVIIIFc has comparable acute efficacy as rFVIII in treating tail clip injury in HemA mice, and fully corrects whole blood clotting time (WBCT) in HemA dogs immediately after dosing. Furthermore, consistent with prolonged half-life, rFVIIIFc shows 2-fold longer prophylactic efficacy in protecting HemA mice from tail vein transection bleeding induced 24-48 hours after dosing. In HemA dogs, rFVIIIFc also sustains partial correction of WBCT 1.5- to 2-fold longer than rFVIII. rFVIIIFc was well tolerated in both species. Thus, the rescue of FVIII by Fc fusion to provide prolonged protection presents a novel pathway for FVIII catabolism, and warrants further investigation. PMID:22246033

  13. 75 FR 52528 - FC Landfill Energy, LLC; Supplemental Notice That Initial Market-Based Rate Filing Includes...

    Science.gov (United States)

    2010-08-26

    ... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Docket No. ER10-2268-000] FC Landfill Energy, LLC; Supplemental Notice That Initial Market- Based Rate Filing Includes Request for Blanket... proceeding, of FC Landfill Energy, LLC's application for market-based rate authority, with an accompanying...

  14. Human IgG lacking effector functions demonstrate lower FcRn-binding and reduced transplacental transport

    NARCIS (Netherlands)

    Stapleton, Nigel M.; Armstrong-Fisher, Sylvia S.; Andersen, Jan Terje; van der Schoot, C. Ellen; Porter, Charlene; Page, Kenneth R.; Falconer, Donald; de Haas, Masja; Williamson, Lorna M.; Clark, Michael R.; Vidarsson, Gestur; Armour, Kathryn L.

    2018-01-01

    We have previously generated human IgG1 antibodies that were engineered for reduced binding to the classical Fcγ receptors (FcγRI-III) and C1q, thereby eliminating their destructive effector functions (constant region G1Δnab). In their potential use as blocking agents, favorable binding to the

  15. Mycoplasma infection of cell lines can simulate the expression of Fc receptors by binding of the carbohydrate moiety of antibodies.

    Science.gov (United States)

    Lemke, H; Krausse, R; Lorenzen, J; Havsteen, B

    1985-05-01

    During the production of Fc receptor (FcR)-bearing hybridomas it was observed with a particular monoclonal anti-sheep red blood cell antibody (anti-SRBC 1/5, IgG1) that the contamination with Mycoplasma arginini of in vitro cultured cell lines leads to an apparent FcR activity. This property did not correspond with the serological typing since other antibodies of the same isotype could not support FcR rosette formation. Another mycoplasma strain M. orale lacked this property. Analysis of the binding reaction revealed that M. arginini contains a lectin which binds the carbohydrate moiety of the anti-SRBC 1/5 antibody, i.e. anti-SRBC 1/5 synthesized under the influence of tunicamycin or deglycosylated by NaIO4 oxidation did not support rosette formation. These data suggest that binding of antibodies to certain mycoplasma strains may be a pathogenic factor during mycoplasma infections by masking the microorganisms with the host's own defense molecules. The experiments with M. arginini-infected cell lines gain immunological importance since we obtained identical results with staphylococcal protein A, as another bacteriological FcR, and cell lines expressing intrinsic membrane FcR. Although it is an open question whether the glycoconjugates are directly bound by the FcR or else by influencing the three-dimensional structure of the antibodies, it seems possible that FcR in general may be lectins.

  16. Momentum flux associated with gravity waves in the low-latitude troposphere

    Directory of Open Access Journals (Sweden)

    S. R. Prabhakaran Nayar

    Full Text Available The vertical fluxes of horizontal momentum at tropospheric heights are calculated for four days, 25–28 August 1999. The mean zonal wind during these days show the presence of strong westward wind at the upper troposphere. Both the symmetric beam radar method and the power spectral method of evaluation of vertical flux of zonal and meridional momentum shows nearly the same result for quiet conditions. The temporal evolution of the momentum flux is estimated for a day with strong zonal shear and convection. These results indicate that on 28 August 1999, the strong downward vertical wind in the lower altitude range is associated with upward vertical flux of zonal momentum, and strong upward vertical wind is associated with downward vertical flux. Similarly, the strong shear in zonal wind is associated with the increase in negative values in vertical flux in the upper troposphere. Analysis of the role of wave periods in the transport of momentum flux indicates that the vertical momentum flux magnitude is not evenly distributed in all wave periods, but instead it peaks at certain wave periods in the range 10 to 100 min.

    Key words. Meteorology and atmospheric dynamics (convective process; tropical meteorology; precipitation

  17. Inhibition of B cell proliferation by antisense DNA to both alpha and beta forms of Fc epsilon R II.

    Science.gov (United States)

    Bhatti, L; Behle, K; Stevens, R H

    1992-10-01

    Epstein-Barr Virus (EBV) infection activates B lymphocyte proliferation through partially understood mechanisms, resulting in phenotypic changes, including the appearance of new antigens. One such antigen is Fc epsilon R II/CD-23 which may be relevant for B cell proliferation. We have used anti-sense oligonucleotides to study the importance of the two forms of this molecule for proliferation in the EBV-transformed, Fc epsilon R II +ve lymphoblastoid B cell line, RPMI 8866. Anti-sense oligodeoxynucleotides were generated to the two forms of Fc epsilon R II; Fc epsilon R IIa (alpha) and IIb (beta) which differ only in their intracytoplasmic domains. Addition of increasing concentrations of anti-sense oligonucleotides, ranging from 1 to 30 microM, significantly decreased cellular proliferation as measured by the incorporation of [3H]thymidine (inhibition range 8-88%). Optimum inhibition of cellular proliferation was apparent at 15 microM concentration of both anti-sense Fc epsilon R IIa and IIb (Fc epsilon R IIa, mean +/- SE = 75 +/- 7% inhibition, p less than 0.001; Fc epsilon R IIb, mean +/- SE = 71 +/- 7% inhibition, p less than 0.001). Anti-sense oligonucleotides complementary to the common part of Fc epsilon R II resulted in a similar inhibition of proliferation. Sense oligonucleotides did not induce significant inhibition. Preincubation of sense and anti-sense oligonucleotides resulted in an abrogation of proliferation inhibition. Moreover, none of these oligonucleotides had any effect on a Fc epsilon R II -ve cell line. Incubation with both anti-sense IIa and IIb resulted in additive, but not synergistic inhibition of proliferation. Addition of soluble Fc epsilon R II did not reverse inhibition of proliferation, suggesting that membrane-bound or intracellular rather than soluble Fc epsilon R II was important for the induced proliferation. Analysis of cell surface expression for Fc epsilon II indicated that while there was a pronounced effect on cell number

  18. fcGENE: a versatile tool for processing and transforming SNP datasets.

    Directory of Open Access Journals (Sweden)

    Nab Raj Roshyara

    Full Text Available Modern analysis of high-dimensional SNP data requires a number of biometrical and statistical methods such as pre-processing, analysis of population structure, association analysis and genotype imputation. Software used for these purposes often rely on specific and incompatible input and output data formats. Therefore extensive data management including multiple format conversions is necessary during analyses.In order to support fast and efficient management and bio-statistical quality control of high-dimensional SNP data, we developed the publically available software fcGENE using C++ object-oriented programming language. This software simplifies and automates the use of different existing analysis packages, especially during the workflow of genotype imputations and corresponding analyses.fcGENE transforms SNP data and imputation results into different formats required for a large variety of analysis packages such as PLINK, SNPTEST, HAPLOVIEW, EIGENSOFT, GenABEL and tools used for genotype imputation such as MaCH, IMPUTE, BEAGLE and others. Data Management tasks like merging, splitting, extracting SNP and pedigree information can be performed. fcGENE also supports a number of bio-statistical quality control processes and quality based filtering processes at SNP- and sample-wise level. The tool also generates templates of commands required to run specific software packages, especially those required for genotype imputation. We demonstrate the functionality of fcGENE by example workflows of SNP data analyses and provide a comprehensive manual of commands, options and applications.We have developed a user-friendly open-source software fcGENE, which comprehensively supports SNP data management, quality control and analysis workflows. Download statistics and corresponding feedbacks indicate that software is highly recognised and extensively applied by the scientific community.

  19. Fc-fusion technology and recombinant FVIII and FIX in the management of the hemophilias.

    Science.gov (United States)

    Mancuso, Maria Elisa; Mannucci, Pier Mannuccio

    2014-01-01

    Prophylaxis with regular infusions of factor VIII (FVIII)- or factor IX (FIX)- containing products is the mainstay of modern hemophilia care. However, this therapeutic regimen is inconvenient, requiring repeated intravenous injections from childhood. Approaches meant to prolong the half-life of FVIII and FIX in plasma have been developed in order to improve the feasibility and acceptability of replacement therapy, extending protection from bleeding, reducing infusion frequency and hence the need for venous access devices in young children. Several strategies have been implemented to enhance the pharmacokinetics of clotting factors, including conjugation with polyethylene glycol and the production by genetic engineering of fusion proteins containing the coagulation factors linked to a long-lived plasma protein such as albumin or the Fc fragment of immunoglobulin (Ig)G. The latter technology is one of the most promising, since the prolongation of FVIII and FIX half-life is obtained by exploiting the physiological binding of the Fc domain to the neonatal Fc receptor. Fc fusion monomers have been obtained with both recombinant FVIII (rFVIIIFc) and FIX (rFIXFc), and data from preclinical and clinical studies showed improved pharmacokinetics for both factors, which are produced in human embryonic kidney (HEK) 293 cells, thus ensuring full human post-translational modifications. In Phase I/IIa studies, rFVIIIFc and rFIXFc showed 1.5-1.7 fold and 3.0-4.0 fold longer elimination half-life, respectively. Similar data have been obtained in the Phase III clinical studies with rFVIIIFc and rFIX-Fc published recently. Both drugs were satisfactorily safe, particularly with respect to immunogenicity, and no serious adverse event was observed.

  20. Altered polymorphonuclear leukocyte Fc gamma R expression contributes to decreased candicidal activity during intraabdominal sepsis

    International Nuclear Information System (INIS)

    Simms, H.H.; D'Amico, R.; Monfils, P.; Burchard, K.W.

    1991-01-01

    We investigated the effects of untreated intraabdominal sepsis on polymorphonuclear leukocyte (PMN) candicidal activity. Two groups of swine were studied. Group I (n=6) underwent sham laparotomy, group II (n=7) underwent cecal ligation and incision. Untreated intraabdominal sepsis resulted in a progressive decrease in PMN candicidal activity. Concomitant rosetting and phagocytosis assays demonstrated a decrease in both the attachment and phagocytosis of Candida albicans opsonized with both normal and septic swine serum by PMNs in group II. Iodine 125-labeled swine immunoglobulin G (IgG) and fluorescein isothioalanate (FITC)-labeled swine IgG were used to investigate Fc gamma receptor ligand interactions. Scatchard analyses demonstrated a progressive decline in both the binding affinity constant and number of IgG molecules bound per PMN. Stimulation of the oxidative burst markedly reduced 125I-labeled IgG binding in both group I and group II, with a greater decrement being seen in animals with intraabdominal sepsis. Further, in group II, PMN recycling of the Fc gamma receptor to the cell surface after generation of the oxidative burst was reduced by postoperative day 4. Binding of monoclonal antibodies to Fc gamma receptor II, but not Fc gamma receptor I/III markedly reduced intracellular candicidal activity. Immunofluorescence studies revealed a homogeneous pattern of FITC-IgG uptake by nearly all group I PMNs, whereas by postoperative day 8 a substantial number of PMNs from group II failed to internalize the FITC-IgG. These studies suggest that untreated intraabdominal sepsis reduces PMN candicidal activity and that this is due, in part, to altered PMN Fc gamma receptor ligand interactions

  1. Clustering of Emerging Flux

    Science.gov (United States)

    Ruzmaikin, A.

    1997-01-01

    Observations show that newly emerging flux tends to appear on the Solar surface at sites where there is flux already. This results in clustering of solar activity. Standard dynamo theories do not predict this effect.

  2. Burnout heat flux in natural flow boiling

    International Nuclear Information System (INIS)

    Helal, M.M.; Darwish, M.A.; Mahmoud, S.I.

    1978-01-01

    Twenty runs of experiments were conducted to determine the critical heat flux for natural flow boiling with water flowing upwards through annuli of centrally heated stainless steel tube. The test section has concentric heated tube of 14mm diameter and heated lengthes of 15 and 25 cm. The outside surface of the annulus was formed by various glass tubes of 17.25, 20 and 25.9mm diameter. System pressure is atmospheric. Inlet subcooling varied from 18 to 5 0 C. Obtained critical heat flux varied from 24.46 to 62.9 watts/cm 2 . A number of parameters having dominant influence on the critical heat flux and hydrodynamic instability (flow and pressure oscillations) preceeding the burnout have been studied. These parameters are mass flow rate, mass velocity, throttling, channel geometry (diameters ratio, length to diameter ratio, and test section length), and inlet subcooling. Flow regimes before and at the moments of burnout were observed, discussed, and compared with the existing physical model of burnout

  3. IgG receptor FcγRIIB plays a key role in obesity-induced hypertension.

    Science.gov (United States)

    Sundgren, Nathan C; Vongpatanasin, Wanpen; Boggan, Brigid-Meghan D; Tanigaki, Keiji; Yuhanna, Ivan S; Chambliss, Ken L; Mineo, Chieko; Shaul, Philip W

    2015-02-01

    There is a well-recognized association between obesity, inflammation, and hypertension. Why obesity causes hypertension is poorly understood. We previously demonstrated using a C-reactive protein (CRP) transgenic mouse that CRP induces hypertension that is related to NO deficiency. Our prior work in cultured endothelial cells identified the Fcγ receptor IIB (FcγRIIB) as the receptor for CRP whereby it antagonizes endothelial NO synthase. Recognizing known associations between CRP and obesity and hypertension in humans, in the present study we tested the hypothesis that FcγRIIB plays a role in obesity-induced hypertension in mice. Using radiotelemetry, we first demonstrated that the hypertension observed in transgenic mouse-CRP is mediated by the receptor, indicating that FcγRIIB is capable of modifying blood pressure. We then discovered in a model of diet-induced obesity yielding equal adiposity in all study groups that whereas FcγRIIB(+/+) mice developed obesity-induced hypertension, FcγRIIB(-/-) mice were fully protected. Levels of CRP, the related pentraxin serum amyloid P component which is the CRP-equivalent in mice, and total IgG were unaltered by diet-induced obesity; FcγRIIB expression in endothelium was also unchanged. However, whereas IgG isolated from chow-fed mice had no effect, IgG from high-fat diet-fed mice inhibited endothelial NO synthase in cultured endothelial cells, and this was an FcγRIIB-dependent process. Thus, we have identified a novel role for FcγRIIB in the pathogenesis of obesity-induced hypertension, independent of processes regulating adiposity, and it may entail an IgG-induced attenuation of endothelial NO synthase function. Approaches targeting FcγRIIB may potentially offer new means to treat hypertension in obese individuals. © 2014 American Heart Association, Inc.

  4. Human IgG lacking effector functions demonstrate lower FcRn-binding and reduced transplacental transport.

    Science.gov (United States)

    Stapleton, Nigel M; Armstrong-Fisher, Sylvia S; Andersen, Jan Terje; van der Schoot, C Ellen; Porter, Charlene; Page, Kenneth R; Falconer, Donald; de Haas, Masja; Williamson, Lorna M; Clark, Michael R; Vidarsson, Gestur; Armour, Kathryn L

    2018-03-01

    We have previously generated human IgG1 antibodies that were engineered for reduced binding to the classical Fcγ receptors (FcγRI-III) and C1q, thereby eliminating their destructive effector functions (constant region G1Δnab). In their potential use as blocking agents, favorable binding to the neonatal Fc receptor (FcRn) is important to preserve the long half-life typical of IgG. An ability to cross the placenta, which is also mediated, at least in part, by FcRn is desirable in some indications, such as feto-maternal alloimmune disorders. Here, we show that G1Δnab mutants retain pH-dependent binding to human FcRn but that the amino acid alterations reduce the affinity of the IgG1:FcRn interaction by 2.0-fold and 1.6-fold for the two antibodies investigated. The transport of the modified G1Δnab mutants across monolayers of human cell lines expressing FcRn was approximately 75% of the wild-type, except that no difference was observed with human umbilical vein endothelial cells. G1Δnab mutation also reduced transport in an ex vivo placenta model. In conclusion, we demonstrate that, although the G1Δnab mutations are away from the FcRn-binding site, they have long-distance effects, modulating FcRn binding and transcellular transport. Our findings have implications for the design of therapeutic human IgG with tailored effector functions. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

  5. Advances in therapeutic Fc engineering - modulation of IgG associated effector functions and serum half-life

    Directory of Open Access Journals (Sweden)

    Abhishek Saxena

    2016-12-01

    Full Text Available Today monoclonal immunoglobulin gamma (IgG antibodies have become a major option in cancer therapy especially for the patients with advanced or metastatic cancers. Efficacy of monoclonal antibodies (mAbs are achieved through both its antigen binding fragment (Fab and crystallizable fragment (Fc. Fab can specifically recognize tumor associated antigen (TAA and thus modulate TAA-linked downstream signaling pathways that may lead to inhibition of tumor growth, induction of tumor apoptosis and differentiation. The Fc region can further improve mAbs’ efficacy by mediating effector functions such as antibody-dependent cellular cytotoxicity (ADCC, complement-dependent cytotoxicity (CDC and antibody dependent cell-mediated phagocytosis (ADCP. Moreover, Fc is the region interacting with the neonatal Fc receptor (FcRn in a pH-dependent manner that can slow down IgG’s degradation and extend its serum half-life. Loss of the antibody Fc region dramatically shortens its serum half-life and weakens its anti-cancer effects. Given the essential roles that the Fc region plays in the modulation of the efficacy of mAb in cancer treatment, Fc engineering has been extensively studied in the past years. This review focuses on the recent advances in therapeutic Fc engineering that modulates its related effector functions and serum half-life. We also discuss the progress made in aglycosylated mAb development that may substantially reduce cost of manufacture but maintain similar efficacies as conventional glycosylated mAb. Finally, we highlight several Fc engineering based mAbs under clinical trials.

  6. IgG Receptor FcγRIIB Plays a Key Role in Obesity-Induced Hypertension

    Science.gov (United States)

    Sundgren, Nathan C.; Vongpatanasin, Wanpen; Boggan, Brigid-Meghan D.; Tanigaki, Keiji; Yuhanna, Ivan S.; Chambliss, Ken L.; Mineo, Chieko; Shaul, Philip W.

    2015-01-01

    There is a well-recognized association between obesity, inflammation, and hypertension. Why obesity causes hypertension is poorly understood. We previously demonstrated using a C-reactive protein (CRP) transgenic mouse that CRP induces hypertension that is related to NO deficiency. Our prior work in cultured endothelial cells identified the Fcγ receptor IIB (FcγRIIB) as the receptor for CRP whereby it antagonizes endothelial NO synthase. Recognizing known associations between CRP and obesity and hypertension in humans, in the present study we tested the hypothesis that FcγRIIB plays a role in obesity-induced hypertension in mice. Using radiotelemetry, we first demonstrated that the hypertension observed in transgenic mouse-CRP is mediated by the receptor, indicating that FcγRIIB is capable of modifying blood pressure. We then discovered in a model of diet-induced obesity yielding equal adiposity in all study groups that whereas FcγRIIB+/+ mice developed obesity-induced hypertension, FcγRIIB−/− mice were fully protected. Levels of CRP, the related pentraxin serum amyloid P component which is the CRP-equivalent in mice, and total IgG were unaltered by diet-induced obesity; FcγRIIB expression in endothelium was also unchanged. However, whereas IgG isolated from chow-fed mice had no effect, IgG from high-fat diet–fed mice inhibited endothelial NO synthase in cultured endothelial cells, and this was an FcγRIIB-dependent process. Thus, we have identified a novel role for FcγRIIB in the pathogenesis of obesity-induced hypertension, independent of processes regulating adiposity, and it may entail an IgG-induced attenuation of endothelial NO synthase function. Approaches targeting FcγRIIB may potentially offer new means to treat hypertension in obese individuals. PMID:25368023

  7. DOWNWARD CATASTROPHE OF SOLAR MAGNETIC FLUX ROPES

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Quanhao; Wang, Yuming; Hu, Youqiu; Liu, Rui, E-mail: zhangqh@mail.ustc.edu.cn [CAS Key Laboratory of Geospace Environment, Department of Geophysics and Planetary Sciences, University of Science and Technology of China, Hefei 230026 (China)

    2016-07-10

    2.5-dimensional time-dependent ideal magnetohydrodynamic (MHD) models in Cartesian coordinates were used in previous studies to seek MHD equilibria involving a magnetic flux rope embedded in a bipolar, partially open background field. As demonstrated by these studies, the equilibrium solutions of the system are separated into two branches: the flux rope sticks to the photosphere for solutions at the lower branch but is suspended in the corona for those at the upper branch. Moreover, a solution originally at the lower branch jumps to the upper, as the related control parameter increases and reaches a critical value, and the associated jump is here referred to as an upward catastrophe. The present paper advances these studies in three aspects. First, the magnetic field is changed to be force-free; the system still experiences an upward catastrophe with an increase in each control parameter. Second, under the force-free approximation, there also exists a downward catastrophe, characterized by the jump of a solution from the upper branch to the lower. Both catastrophes are irreversible processes connecting the two branches of equilibrium solutions so as to form a cycle. Finally, the magnetic energy in the numerical domain is calculated. It is found that there exists a magnetic energy release for both catastrophes. The Ampère's force, which vanishes everywhere for force-free fields, appears only during the catastrophes and does positive work, which serves as a major mechanism for the energy release. The implications of the downward catastrophe and its relevance to solar activities are briefly discussed.

  8. DOWNWARD CATASTROPHE OF SOLAR MAGNETIC FLUX ROPES

    International Nuclear Information System (INIS)

    Zhang, Quanhao; Wang, Yuming; Hu, Youqiu; Liu, Rui

    2016-01-01

    2.5-dimensional time-dependent ideal magnetohydrodynamic (MHD) models in Cartesian coordinates were used in previous studies to seek MHD equilibria involving a magnetic flux rope embedded in a bipolar, partially open background field. As demonstrated by these studies, the equilibrium solutions of the system are separated into two branches: the flux rope sticks to the photosphere for solutions at the lower branch but is suspended in the corona for those at the upper branch. Moreover, a solution originally at the lower branch jumps to the upper, as the related control parameter increases and reaches a critical value, and the associated jump is here referred to as an upward catastrophe. The present paper advances these studies in three aspects. First, the magnetic field is changed to be force-free; the system still experiences an upward catastrophe with an increase in each control parameter. Second, under the force-free approximation, there also exists a downward catastrophe, characterized by the jump of a solution from the upper branch to the lower. Both catastrophes are irreversible processes connecting the two branches of equilibrium solutions so as to form a cycle. Finally, the magnetic energy in the numerical domain is calculated. It is found that there exists a magnetic energy release for both catastrophes. The Ampère's force, which vanishes everywhere for force-free fields, appears only during the catastrophes and does positive work, which serves as a major mechanism for the energy release. The implications of the downward catastrophe and its relevance to solar activities are briefly discussed.

  9. Controls of evapotranspiration and CO2 fluxes from scots pine by surface conductance and abiotic factors.

    Directory of Open Access Journals (Sweden)

    Tianshan Zha

    Full Text Available Evapotranspiration (E and CO2 flux (Fc in the growing season of an unusual dry year were measured continuously over a Scots pine forest in eastern Finland, by eddy covariance techniques. The aims were to gain an understanding of their biological and environmental control processes. As a result, there were obvious diurnal and seasonal changes in E, Fc , surface conductance (gc , and decoupling coefficient (Ω, showing similar trends to those in radiation (PAR and vapour pressure deficit (δ. The maximum mean daily values (24-h average for E, Fc , gc , and Ω were 1.78 mmol m(-2 s(-1, -11.18 µmol m(-2 s(-1, 6.27 mm s(-1, and 0.31, respectively, with seasonal averages of 0.71 mmol m(-2 s(-1, -4.61 µmol m(-2 s(-1, 3.3 mm s(-1, and 0.16. E and Fc were controlled by combined biological and environmental variables. There was curvilinear dependence of E on gc and Fc on gc . Among the environmental variables, PAR was the most important factor having a positive linear relationship to E and curvilinear relationship to Fc , while vapour pressure deficit was the most important environmental factor affecting gc . Water use efficiency was slightly higher in the dry season, with mean monthly values ranging from 6.67 to 7.48 μmol CO2 (mmol H2O(-1 and a seasonal average of 7.06 μmol CO2 (μmol H2O(-1. Low Ω and its close positive relationship with gc indicate that evapotranspiration was sensitive to surface conductance. Mid summer drought reduced surface conductance and decoupling coefficient, suggesting a more biotic control of evapotranspiration and a physiological acclimation to dry air. Surface conductance remained low and constant under dry condition, supporting that a constant value of surface constant can be used for modelling transpiration under drought condition.

  10. Far-zone contributions of airborne gravity anomalies' upward/downward continuation

    Directory of Open Access Journals (Sweden)

    Boyang Zhou

    2016-11-01

    Full Text Available Airborne gravimetry has become a vital technique in local gravity field approximation, and upward/downward continuation of gravity data is a key process of airborne gravimetry. In these procedures, the integral domain is divided into two parts, namely the near-zone and the far-zone. The far-zone contributions are approximated by the truncation coefficients and a global geo-potential model, and their values are controlled by several issues. This paper investigates the effects of flight height, the size of near-zone cap, and Remove-Compute-Restore (RCR technique upon far-zone contributions. Results show that at mountainous area the far-zone contributions can be ignored when EIGEN-6C of 360 degree is removed from the gravity data, together with a near-zone cap of 1° and a flight height less than 10 km, while at flat area EIGEN-6C of 180 degree is feasible.

  11. A study of upward going particles with the Extreme Energy Events telescopes

    Energy Technology Data Exchange (ETDEWEB)

    Abbrescia, M. [Museo Storico della Fisica e Centro Studi e Ricerche E. Fermi, Roma (Italy); INFN and Dipartimento di Fisica, Università di Bari, Bari (Italy); Avanzini, C.; Baldini, L. [Museo Storico della Fisica e Centro Studi e Ricerche E. Fermi, Roma (Italy); INFN and Dipartimento di Fisica, Università di Pisa, Pisa (Italy); Ferroli, R. Baldini [Museo Storico della Fisica e Centro Studi e Ricerche E. Fermi, Roma (Italy); INFN Laboratori Nazionali di Frascati, Frascati (RM) (Italy); Batignani, G. [Museo Storico della Fisica e Centro Studi e Ricerche E. Fermi, Roma (Italy); INFN and Dipartimento di Fisica, Università di Pisa, Pisa (Italy); Bencivenni, G. [INFN Laboratori Nazionali di Frascati, Frascati (RM) (Italy); Bossini, E. [Museo Storico della Fisica e Centro Studi e Ricerche E. Fermi, Roma (Italy); INFN Gruppo Collegato di Siena and Dipartimento di Fisica, Università di Siena, Siena (Italy); Chiavassa, A. [INFN and Dipartimento di Fisica, Università di Torino, Torino (Italy); Cicalo, C. [Museo Storico della Fisica e Centro Studi e Ricerche E. Fermi, Roma (Italy); INFN and Dipartimento di Fisica, Università di Cagliari, Cagliari (Italy); Cifarelli, L. [Museo Storico della Fisica e Centro Studi e Ricerche E. Fermi, Roma (Italy); INFN and Dipartimento di Fisica, Università di Bologna, Bologna (Italy); Coccia, E. [INFN and Dipartimento di Fisica, Università di Roma Tor Vergata, Roma (Italy); Corvaglia, A. [Museo Storico della Fisica e Centro Studi e Ricerche E. Fermi, Roma (Italy); INFN and Dipartimento di Matematica e Fisica, Università del Salento, Lecce (Italy); and others

    2016-04-21

    In this paper the first study of the upward going events detected by the telescopes of the Extreme Energy Event (EEE) project is reported. The EEE project consists of a detector array of Multigap Resistive Plate Chambers located at selected sites on the Italian territory. During autumn 2014 the first coordinated data taking period took place and around one billion candidate tracks were collected. Among them, of particular interest is the sample of particles which cross the telescopes from below. The results obtained demonstrate that the EEE telescopes can distinguish the electrons produced as decay products of cosmic muons stopped in the ground, or in the last chamber of the telescopes themselves, confirming the excellent performance of the system for the investigation of intriguing cosmic phenomena.

  12. Two-phase upward air water flow in a prismatic channel with rectangular base

    International Nuclear Information System (INIS)

    Carvalho Tofani, P. de

    1984-01-01

    Two-phase liquid-gas mixtures provide suitable means to simulate water-water vapor flows, which may occur in nuclear reactor cores. The mastery of physical transport phenomena is of great importance, as far as the analysis of such thermal systems is concerned. Within the framework of thermal-hydraulic programs, experiments have been carried out to investigate the two-phase upward air-water flow structure, in a rectangular test section, by using independent measuring techniques, which comprise direct viewing and photography, electrical probes and gamma-ray attenuation. In this paper, flow pattern maps and correlations for flow pattern transitions, void fraction profiles, liquid film thickness and superficial average void fraction are proposed and compared to available data. (Author) [pt

  13. CrossRef A study of upward going particles with the Extreme Energy Events telescopes

    CERN Document Server

    Abbrescia, M; Baldini, L; Ferroli, R Baldini; Batignani, G; Bencivenni, G; Bossini, E; Chiavassa, A; Cicalo, C; Cifarelli, L; Coccia, E; Corvaglia, A; De Gruttola, D; De Pasquale, S; Di Giovanni, A; D׳Incecco, M; Dreucci, M; Fabbri, F L; Fattibene, E; Ferraro, A; Forster, R; Frolov, V; Galeotti, P; Garbini, M; Gemme, G; Gnesi, I; Grazzi, S; Gustavino, C; Hatzifotiadu, D; La Rocca, P; Maggiora, A; Maron, G; Mazziotta, M N; Miozzi, S; Nania, R; Noferini, F; Nozzoli, F; Panareo, M; Panetta, M P; Paoletti, R; Perasso, L; Pilo, F; Piragino, G; Riggi, F; Righini, G C; Rodriguez, A R; Sartorelli, G; Scapparone, E; Schioppa, M; Scribano, A; Selvi, M; Serci, S; Siddi, E; Squarcia, S; Stori, L; Taiuti, M; Terreni, G; Vistoli, M C; Votano, L; Williams, M C S; Zani, S; Zichichi, A; Zuyeuski, R

    2016-01-01

    In this paper the first study of the upward going events detected by the telescopes of the Extreme Energy Event (EEE) project is reported. The EEE project consists of a detector array of Multigap Resistive Plate Chambers located at selected sites on the Italian territory. During autumn 2014 the first coordinated data taking period took place and around one billion candidate tracks were collected. Among them, of particular interest is the sample of particles which cross the telescopes from below. The results obtained demonstrate that the EEE telescopes can distinguish the electrons produced as decay products of cosmic muons stopped in the ground, or in the last chamber of the telescopes themselves, confirming the excellent performance of the system for the investigation of intriguing cosmic phenomena.

  14. Internal causes of radon and its daughters upward migration and cluster phenomenon

    International Nuclear Information System (INIS)

    Jia Wenyi; Fang Fang; Zhou Rongsheng; Ma Yingjie; Qiu Yuande; Hou Xinsheng; Wu Yunping; Zu Xiulan; Wang Xiaoqin

    1999-01-01

    Radon and its daughters have a very big specific gravity. But under laboratory conditions, they have the ability to migrate upward. The phenomenon can't be interpreted by an external cause but by an internal cause. The mechanism is that radon and most of its daughters and parents are decaying bodies able to radiate α-particles. After deceleration, 4He can combine with radon and its daughters and parents to form clusters. When the buoyancy of air is greater than the gravity of the clusters, self-ascending occurs. Accordingly, the distance that Rn covered during 3.825 days (Rn half-life) should not be regarded as Rn and its daughters migrating distance, but should be calculated according to all effects. That clusters can be formed by 4He, Rn and its daughters are valuable to study because of the similarity between Rn and heavy metal particles

  15. A study of upward going particles with the Extreme Energy Events telescopes

    International Nuclear Information System (INIS)

    Abbrescia, M.; Avanzini, C.; Baldini, L.; Ferroli, R. Baldini; Batignani, G.; Bencivenni, G.; Bossini, E.; Chiavassa, A.; Cicalo, C.; Cifarelli, L.; Coccia, E.; Corvaglia, A.

    2016-01-01

    In this paper the first study of the upward going events detected by the telescopes of the Extreme Energy Event (EEE) project is reported. The EEE project consists of a detector array of Multigap Resistive Plate Chambers located at selected sites on the Italian territory. During autumn 2014 the first coordinated data taking period took place and around one billion candidate tracks were collected. Among them, of particular interest is the sample of particles which cross the telescopes from below. The results obtained demonstrate that the EEE telescopes can distinguish the electrons produced as decay products of cosmic muons stopped in the ground, or in the last chamber of the telescopes themselves, confirming the excellent performance of the system for the investigation of intriguing cosmic phenomena.

  16. Peritoneal catheter fixation combined with straight upward tunnel and low implant position to prevent catheter malfunction.

    Science.gov (United States)

    Zhang, Qingyan; Jiang, Chunming; Zhu, Wei; Sun, Cheng; Xia, Yangyang; Tang, Tianfeng; Wan, Cheng; Shao, Qiuyuan; Liu, Jing; Jin, Bo; Zhang, Miao

    2018-03-01

    Catheter malfunction is the main reason for early peritoneal dialysis (PD) technique failure. This study aimed to evaluate the effect of a new surgery technique with catheter fixation to the lower abdominal wall combined with straight upward tunnel and low implant position in reducing catheter malfunction. Patients with end stage renal disease who received PD in our centre from January 2013 to December 2015 were involved in this study. They were randomly divided into three groups according to surgical technique: traditional open surgery group, modified open surgery group and modified open surgery with catheter fixation group. All patients were followed up for six months after surgery. Catheter- related complications were analyzed. A total of 152 patients were involved. Among them, 49 received traditional open surgery (TOS group), 49 received modified open surgery (MOS group), and 54 received modified open surgery with catheter fixation (MOS-F group). During follow-up, no patients (0%) in MOS-F group developed catheter malfunction which was significantly lower than that of the TOS group (0 vs 16.33%, P = 0.002). Although not statistically significant, the incidence of catheter malfunction was lower in MOS-F group than that in MOS group (0 vs 4.08%, P = 0.134). No significant difference was observed in the episodes of infection, bleeding, leakage, inflow or outflow pain, hernia and delayed wound healing among the three groups (all P > 0.05). Catheter fixation combined with straight upward tunnel and low implant position can effectively prevent catheter malfunction in PD catheter placement. © 2016 Asian Pacific Society of Nephrology.

  17. The influence of the unsaturated zone on the upward transport of radionuclides in soils

    International Nuclear Information System (INIS)

    Elert, M.; Lindgren, M.

    1993-07-01

    The transport of radionuclides from the deep soil to the surface soil is an important part of biosphere modelling. In this study the effect of transient hydrological conditions on the upward transport of radionuclides through soils has been studied. The effect of varying soil properties, climate conditions have been considered as well as the effect of a fluctuating groundwater level. It was shown that the soil characteristics influences the radionuclide concentration; an increased hydraulic conductivity leads to increase in the concentration in the root zone. The climate conditions were shown to be of major importance. A dispersion dependent on both velocity and saturation leads to a more effective upward transport of radionuclides to the root zone than if dispersion is assumed to be dependent only on the saturation. The boundary condition used in the case with varying groundwater level may be more realistic than the boundary condition applied for the case with a constant groundwater level. All calculations with varying groundwater level gave lower radionuclide concentration in the root zone. Sorption is redox sensitive for many radionuclides and the redox potential in the soil will be affected by the degree of water saturation. The performed calculations did, however, not result in any significant change in the radionuclide concentration in the root zone due to variation in sorption. A comparison between the results of the two models show that the compartment model in all studied cases predicts a higher annual average radionuclide concentration in the root zone than the numerical model. Annual variation in soil water flow were not included in the compartment model. During the summer the concentration in the root zone may be several times higher than the annual average. This may be important for plant uptake, since this increased concentrations coincides with the plant growing season. The calculations made with the simple compartment model also show that these

  18. Removal of heavy metals from kaolin using an upward electrokinetic soil remedial (UESR) technology

    International Nuclear Information System (INIS)

    Wang, J.-Y.; Huang, X.-J.; Kao, Jimmy C.M.; Stabnikova, Olena

    2006-01-01

    An upward electrokinetic soil remedial (UESR) technology was proposed to remove heavy metals from contaminated kaolin. Unlike conventional electrokinetic treatment that uses boreholes or trenches for horizontal migration of heavy metals, the UESR technology, applying vertical non-uniform electric fields, caused upward transportation of heavy metals to the top surface of the treated soil. The effects of current density, treatment duration, cell diameter, and different cathode chamber influent (distilled water or 0.01 M nitric acid) were studied. The removal efficiencies of heavy metals positively correlated to current density and treatment duration. Higher heavy metals removal efficiency was observed for the reactor cell with smaller diameter. A substantial amount of heavy metals was accumulated in the nearest to cathode 2 cm layer of kaolin when distilled water was continuously supplied to the cathode chamber. Heavy metals accumulated in this layer of kaolin can be easily excavated and disposed off. The main part of the removed heavy metals was dissolved in cathode chamber influent and moved away with cathode chamber effluent when 0.01 M nitric acid was used, instead of distilled water. Energy saving treatment by UESR technology with highest metal removal efficiencies was provided by two regimes: (1) by application of 0.01 M nitric acid as cathode chamber influent, cell diameter of 100 mm, duration of 18 days, and constant voltage of 3.5 V (19.7 kWh/m 3 of kaolin) and (2) by application of 0.01 M nitric acid as cathode chamber influent, cell diameter of 100 cm, duration of 6 days, and constant current density of 0.191 mA/cm 2 (19.1 kWh/m 3 of kaolin)

  19. A Scientific Calculator for Exact Real Number Computation Based on LRT, GMP and FC++

    Directory of Open Access Journals (Sweden)

    J. A. Hernández

    2012-03-01

    Full Text Available Language for Redundant Test (LRT is a programming language for exact real number computation. Its lazy evaluation mechanism (also called call-by-need and its infinite list requirement, make the language appropriate to be implemented in a functional programming language such as Haskell. However, a direction translation of the operational semantics of LRT into Haskell as well as the algorithms to implement basic operations (addition subtraction, multiplication, division and trigonometric functions (sin, cosine, tangent, etc. makes the resulting scientific calculator time consuming and so inefficient. In this paper, we present an alternative implementation of the scientific calculator using FC++ and GMP. FC++ is a functional C++ library while GMP is a GNU multiple presicion library. We show that a direct translation of LRT in FC++ results in a faster scientific calculator than the one presented in Haskell.El lenguaje de verificación redundante (LRT, por sus siglas en inglés es un lenguaje de programación para el cómputo con números reales exactos. Su método de evaluación lazy (o mejor conocido como llamada por necesidad y el manejo de listas infinitas requerido, hace que el lenguaje sea apropiado para su implementación en un lenguaje funcional como Haskell. Sin embargo, la implementación directa de la semántica operacional de LRT en Haskell así como los algoritmos para funciones básicas (suma, resta, multiplicación y división y funciones trigonométricas (seno, coseno, tangente, etc hace que la calculadora científica resultante sea ineficiente. En este artículo, presentamos una implementación alternativa de la calculadora científica usando FC++ y GMP. FC++ es una librería que utiliza el paradigma Funcional en C++ mientras que GMP es una librería GNU de múltiple precisión. En el artículo mostramos que la implementación directa de LRT en FC++ resulta en una librería más eficiente que la implementada en Haskell.

  20. Upward creep of the heart: A frequent source of false-positive reversible defects during thallium-201 stress-redistribution SPECT

    International Nuclear Information System (INIS)

    Friedman, J.; Van Train, K.; Maddahi, J.; Rozanski, A.; Prigent, F.; Bietendorf, J.; Waxman, A.; Berman, D.S.

    1989-01-01

    A new cause of artifactual 201 Tl defects on single photon emission computed tomography (SPECT) termed upward creep of the heart is described. In 102 consecutive patients undergoing 201 Tl SPECT, 30 (29%) demonstrated upward creep defined by an upward movement of the heart of greater than or equal to 2 pixels during acquisition. In 45 consecutive patients with a less than 5% likelihood of coronary artery disease, 17 (38%) had upward creep. Of these nine had reversible 201 Tl defects localized to the inferior and basal inferoseptal walls, while none of the 28 without upward creep had defects. The 17 low likelihood patients with upward creep had longer exercise duration and higher peak heart rate than those without upward creep. In five additional low likelihood patients with upward creep in whom imaging was immediately repeated, the upward creep pattern disappeared on the repeated images. After we changed our test protocol to begin imaging 15 min postexercise, only five (14%) of 36 low likelihood patients tested demonstrated upward creep. Upward creep is probably related to a transient increase in mean total lung volume early following exhaustive exercise, resulting in a mean lower position of the diaphragm (and thus the heart) at the beginning of imaging. The frequency of this source of false-positive 201 Tl studies can be reduced by delaying SPECT acquisition until 15 min postexercise

  1. Development of a real-time fuel cell stack modelling solution with integrated test rig interface for the generic fuel cell modelling environment (GenFC) software

    Energy Technology Data Exchange (ETDEWEB)

    Fraser, S.D.; Monsberger, M.; Hacker, V. [Graz Univ. of Technology, Graz (Austria). Christian Doppler Laboratory for Fuel Cell Systems; Gubner, A.; Reimer, U. [Forschungszentrum Julich, Julich (Germany)

    2007-07-01

    Since the late 1980s, numerous FC models have been developed by scientists and engineers worldwide to design, control and optimize fuel cells (FCs) and fuel cell (FC) power systems. However, state-of-the-art FC models have only a small range of applications within the versatile field of FC modelling. As fuel cell technology approaches commercialization, the scientific community is faced with the challenge of providing robust fuel cell models that are compatible with established processes in industrial product development. One such process, known as Hardware in the Loop (HiL), requires real-time modelling capability. HiL is used for developing and testing hardware components by adding the complexity of the related dynamic systems with mathematical representations. Sensors and actuators are used to interface simulated and actual hardware components. As such, real-time fuel cell models are among the key elements in the development of the Generic Fuel Cell Modelling Environment (GenFC) software. Six European partners are developing GenFC under the support of the Sixth European Framework Programme for Research and Technological Development (FP6). GenFC is meant to increase the use of fuel cell modelling for systems design and to enable cost- and time-efficient virtual experiments for optimizing operating parameters. This paper presented an overview of the GenFC software and the GenFC HiL functionality. It was concluded that GenFC is going to be an extendable software tool providing FC modelling techniques and solutions to a wide range of different FC modelling applications. By combining the flexibility of the GenFC software with this HiL-specific functionality, GenFC is going to promote the use of FC model-based HiL technology in FC system development. 9 figs.

  2. Fc gamma receptor activation induces the tyrosine phosphorylation of both phospholipase C (PLC)-gamma 1 and PLC-gamma 2 in natural killer cells

    OpenAIRE

    1992-01-01

    Crosslinking of the low affinity immunoglobulin G (IgG) Fc receptor (Fc gamma R type III) on natural killer (NK) cells initiates antibody- dependent cellular cytotoxicity. During this process, Fc gamma R stimulation results in the rapid activation of phospholipase C (PLC), which hydrolyzes membrane phosphoinositides, generating inositol-1,4,5- trisphosphate and sn-1,2-diacylglycerol as second messengers. We have recently reported that PLC activation after Fc gamma R stimulation can be inhibit...

  3. Upward translocation of 14C-amino compounds in xylem and phloem of citrus trees (citrus unshiu marc.)

    International Nuclear Information System (INIS)

    Kato, Tadashi; Yamagata, Makoto; Tsukahara, Sadao

    1985-01-01

    Upward and lateral movements of 14 C-amino compounds in intact trees and excised shoots, and upward translocation of major amino compounds in intact shoots were examined in the early stage of new shoot development. The results were summarized as follows. 1. Uniformly 14 C-labelled arginine, asparagine, aspartic acid and proline were steadily taken up by roots of intact trees, translocated to old leaves and new shoots, and appeared in the fed compound and its metabolized products in these organs. 2. 14 C-arginine, asparagine and proline were translocated upward not only via the xylem but also via the phloem. Lateral movements, from the xylem to the pholoem and from the phloem to the xylem, also occurred. These compounds showed different patterns in their movements. 14 C-arginine and its metabolic products tended to accumulate in the xylem and translocate upward in the xylem. This was in contrast to 14 C-proline and its metabolic products, which tended to accumulate in the phloem and translocate upward in the phloem. These findings were supported by the results obtained in intact shoots. 3. The 14 C-amino compounds were metabolized to soluble and insoluble compounds during the translocation and in the new shoots. However, they differed significantly in the extent of metabolic conversion during translocation; proline was hardly metabolized, arginine and asparagine were moderately metabolized, and aspartic acid was almost completely metabolized. (author)

  4. Autoantibody-induced internalization of CNS AQP4 water channel and EAAT2 glutamate transporter requires astrocytic Fc receptor.

    Science.gov (United States)

    Hinson, Shannon R; Clift, Ian C; Luo, Ningling; Kryzer, Thomas J; Lennon, Vanda A

    2017-05-23

    Aquaporin-4 (AQP4) water channel-specific IgG distinguishes neuromyelitis optica (NMO) from multiple sclerosis and causes characteristic immunopathology in which central nervous system (CNS) demyelination is secondary. Early events initiating the pathophysiological outcomes of IgG binding to astrocytic AQP4 are poorly understood. CNS lesions reflect events documented in vitro following IgG interaction with AQP4: AQP4 internalization, attenuated glutamate uptake, intramyelinic edema, interleukin-6 release, complement activation, inflammatory cell recruitment, and demyelination. Here, we demonstrate that AQP4 internalization requires AQP4-bound IgG to engage an astrocytic Fcγ receptor (FcγR). IgG-lacking Fc redistributes AQP4 within the plasma membrane and induces interleukin-6 release. However, AQP4 endocytosis requires an activating FcγR's gamma subunit and involves astrocytic membrane loss of an inhibitory FcγR, CD32B. Interaction of the IgG-AQP4 complex with FcγRs triggers coendocytosis of the excitatory amino acid transporter 2 (EAAT2). Requirement of FcγR engagement for internalization of two astrocytic membrane proteins critical to CNS homeostasis identifies a complement-independent, upstream target for potential early therapeutic intervention in NMO.

  5. FcγRIIb on myeloid cells rather than on B cells protects from collagen-induced arthritis.

    Science.gov (United States)

    Yilmaz-Elis, A Seda; Ramirez, Javier Martin; Asmawidjaja, Patrick; van der Kaa, Jos; Mus, Anne-Marie; Brem, Maarten D; Claassens, Jill W C; Breukel, Cor; Brouwers, Conny; Mangsbo, Sara M; Boross, Peter; Lubberts, Erik; Verbeek, J Sjef

    2014-06-15

    Extensive analysis of a variety of arthritis models in germline KO mice has revealed that all four receptors for the Fc part of IgG (FcγR) play a role in the disease process. However, their precise cell type-specific contribution is still unclear. In this study, we analyzed the specific role of the inhibiting FcγRIIb on B lymphocytes (using CD19Cre mice) and in the myeloid cell compartment (using C/EBPαCre mice) in the development of arthritis induced by immunization with either bovine or chicken collagen type II. Despite their comparable anti-mouse collagen autoantibody titers, full FcγRIIb knockout (KO), but not B cell-specific FcγRIIb KO, mice showed a significantly increased incidence and severity of disease compared with wild-type control mice when immunized with bovine collagen. When immunized with chicken collagen, disease incidence was significantly increased in pan-myeloid and full FcγRIIb KO mice, but not in B cell-specific KO mice, whereas disease severity was only significantly increased in full FcγRIIb KO mice compared with incidence and severity in wild-type control mice. We conclude that, although anti-mouse collagen autoantibodies are a prerequisite for the development of collagen-induced arthritis, their presence is insufficient for disease development. FcγRIIb on myeloid effector cells, as a modulator of the threshold for downstream Ab effector pathways, plays a dominant role in the susceptibility to collagen-induced arthritis, whereas FcγRIIb on B cells, as a regulator of Ab production, has a minor effect on disease susceptibility. Copyright © 2014 by The American Association of Immunologists, Inc.

  6. Inhibition of th17 cells and promotion of tregs in fc gamma chain-deficient mice contributes to the attenuated atherosclerotic lesions

    Science.gov (United States)

    The presence of anti-oxLDL IgG is well documented in clinical and animal studies. However, the role for Fc Rs to the progression of atherosclerosis has not been studied in detail. In the present study, we investigated the role for activating Fc R in the progression of atherosclerosis using apoE-Fc -...

  7. Fc Gamma Receptor 3B (FCGR3Bc.233C>A-rs5030738) Polymorphism Modifies the Protective Effect of Malaria Specific Antibodies in Ghanaian Children

    DEFF Research Database (Denmark)

    Adu, Bright; Jepsen, Micha Phill Grønholm; Gerds, Thomas A

    2014-01-01

    Immunoglobulin G (IgG) cross-linking with Fc gamma receptor IIIB (FcγRIIIB) triggers neutrophil degranulation, releasing reactive oxygen species with high levels associated with protection against malaria. The FCGR3B-c.233C>A polymorphism thought to influence the interaction between IgG and Fcγ...

  8. Fc-receptors and surface immunoglobulins in cells of the hairy cell leukemia

    Energy Technology Data Exchange (ETDEWEB)

    Rieber, E P; Linke, R P; Riethmueller, G [Tuebingen Univ. (Germany, F.R.). Abt. fuer Experimentelle Chirurgie und Immunologie; Heyden, H.W. von; Waller, H D [Tuebingen Univ. (Germany, F.R.). Abt. Innere Medizin 2

    1976-01-01

    Using /sup 125/I-labelled aggregated IgG in a quantitative assay a strong expression of Fc-receptors was found on the leukemic cells of a patient with hairy cell leukemia. The Fc-receptor activity on these cells was much higher than that on monocytes and B-lymphocytes from normal blood. Surface immunoglobulins were detected by radioautography using radioactively labelled (Fab')/sub 2/-fragments of monospecific antibodies directed against immunoglobulin heavy chains. Prior to radioautography the cells were stained for the tartrate resistant acid phosphatase. It is found that all cells containing this enzyme bore delta-chains on their surface. On more than 90% of these cells a simultaneous expression of ..mu..-chains was detected. ..gamma..-chains could only be demonstrated on cells which were negative for the tartrate resistant acid phosphatase; part of these cells, however, were hairy cells by morphological criteria.

  9. The generation of calandria tube (CT) inner diameter profiles from fuel channel (FC) inspection data

    Energy Technology Data Exchange (ETDEWEB)

    Sedran, P.J., E-mail: paul.sedran@amec.com [AMEC NSS, Toronto, ON (Canada); Rankin, B., E-mail: brankin@nbpower.com [NB Power, Fredericton, NB (Canada); Lemire, C., E-mail: Lemire.Christian@hydro.qc.ca [Hydro-Quebec, Montreal, QC (Canada)

    2015-07-01

    Studies of CT deformation at spacer locations, key to the development of FC deformation modelling, have been limited by the availability of gauging measurements from removed CTs. In [1], it was proposed that CT dimensional profiles could be generated using FC inspection data. Since then, the concept was investigated further by assessing: (1) the normalisation of gap measurements to the diameter of the spacer coil, (2) the validity of gap measurements from inspections of Point Lepreau and Gentilly-2, and the CT dimensional profiles generated from the inspection data.It was concluded, from the work presented in this paper, that the CT-PT gap data and the CT dimensional profiles generated using the data from the two subject inspections are reasonable. (author)

  10. Fc-receptors and surface immunoglobulins in cells of the hairy cell leukemia

    International Nuclear Information System (INIS)

    Rieber, E.P.; Linke, R.P.; Riethmueller, G.; Heyden, H.W. von; Waller, H.D.

    1976-01-01

    Using 125 I-labelled aggregated IgG in a quantitative assay a strong expression of Fc-receptors was found on the leukemic cells of a patient with hairy cell leukemia. The Fc-receptor activity on these cells was much higher than that on monocytes and B-lymphocytes from normal blood. Surface immunoglobulins were detected by radioautography using radioactively labelled (Fab') 2 -fragments of monospecific antibodies directed against immunoglobulin heavy chains. Prior to radioautography the cells were stained for the tartrate resistant acid phosphatase. It is found that all cells containing this enzyme bore delta-chains on their surface. On more than 90% of these cells a simultaneous expression of μ-chains was detected. γ-chains could only be demonstrated on cells which were negative for the tartrate resistant acid phosphatase; part of these cells, however, were hairy cells by morphological criteria. (orig.) [de

  11. Interactions of phagocytes with the Lyme disease spirochete: role of the Fc receptor

    International Nuclear Information System (INIS)

    Benach, J.L.; Fleit, H.B.; Habicht, G.S.; Coleman, J.L.; Bosler, E.M.; Lane, B.P.

    1984-01-01

    The phagocytic capacity of murine and human mononuclear and polymorphonuclear phagocytes (including peripheral blood monocytes and neutrophils), rabbit and murine peritoneal exudate cells, and the murine macrophage cell line P388D1 against the Lyme disease spirochete was studied. All of these cells were capable of phagocytosing the spirochete; phagocytosis was measured by the uptake of radiolabeled spirochetes, the appearance of immunofluorescent bodies in phagocytic cells, and electron microscopy. Both opsonized and nonopsonized organisms were phagocytosed. The uptake of opsonized organisms by neutrophils was blocked by a monoclonal antibody specific for the Fc receptor and by immune complexes; these findings suggested that most phagocytosis is mediated by the Fc receptor. Similarly, the uptake of opsonized organisms by human monocytes was inhibited by human monomeric IgG1 and by immune complexes. These results illustrate the role of immune phagocytosis of spirochetes in host defense against Lyme disease

  12. Advanced Transport Operating System (ATOPS) Flight Management/Flight Controls (FM/FC) software description

    Science.gov (United States)

    Wolverton, David A.; Dickson, Richard W.; Clinedinst, Winston C.; Slominski, Christopher J.

    1993-01-01

    The flight software developed for the Flight Management/Flight Controls (FM/FC) MicroVAX computer used on the Transport Systems Research Vehicle for Advanced Transport Operating Systems (ATOPS) research is described. The FM/FC software computes navigation position estimates, guidance commands, and those commands issued to the control surfaces to direct the aircraft in flight. Various modes of flight are provided for, ranging from computer assisted manual modes to fully automatic modes including automatic landing. A high-level system overview as well as a description of each software module comprising the system is provided. Digital systems diagrams are included for each major flight control component and selected flight management functions.

  13. Hydrodynamic delivery of plasmid DNA encoding human Fc?R-Ig dimers blocks immune-complex mediated inflammation in mice

    OpenAIRE

    Shashidharamurthy, Rangaiah; Machiah, Deepa; Bozeman, Erica N.; Srivatsan, Sanjay; Patel, Jaina; Cho, Alice; Jacob, Joshy; Selvaraj, Periasamy

    2011-01-01

    Therapeutic use and function of recombinant molecules can be studied by the expression of foreign genes in mice. In this study, we have expressed human Fcgamma receptor ?Ig fusion molecules (Fc?R-Igs) in mice by administering Fc?R-Ig plasmid DNAs hydrodynamically and compared their effectiveness to purified molecules in blocking immune-complex (IC) mediated inflammation in mice. The concentration of hydrodynamically expressed Fc?R-Igs (CD16AF-Ig, CD32AR-Ig and CD32AH-Ig) reached a maximum of ...

  14. Increase of lymphocytes with Fc receptors for IgE in patients with allergic rhinitis during the grass pollen season.

    OpenAIRE

    Spiegelberg, H L; Simon, R A

    1981-01-01

    Peripheral blood lymphocytes from 10 nonallergic donors and 7 patients suffering from seasonal allergic rhinitis and receiving desensitization therapy were analyzed by rosette assays for Fc receptors for IgE (Fc epsilon R) and IgG (Fc gamma R) before, during and after the grass pollen season. Six of seven patients had moderately elevated IgE levels (330 +/- 268 IU/ml), all had high titers of skin sensitizing antibodies to grass pollens and serum IgE antibodies as measured by radio-allergosorb...

  15. Detection of serpentine in exogenic carbonaceous chondrite material on Vesta from Dawn FC data

    Science.gov (United States)

    Nathues, Andreas; Hoffmann, Martin; Cloutis, Edward A.; Schäfer, Michael; Reddy, Vishnu; Christensen, Ulrich; Sierks, Holger; Thangjam, Guneshwar Singh; Le Corre, Lucille; Mengel, Kurt; Vincent, Jean-Baptist; Russell, Christopher T.; Prettyman, Tom; Schmedemann, Nico; Kneissl, Thomas; Raymond, Carol; Gutierrez-Marques, Pablo; Hall, Ian; Büttner, Irene

    2014-09-01

    The Dawn mission’s Framing Camera (FC) observed Asteroid (4) Vesta in 2011 and 2012 using seven color filters and one clear filter from different orbits. In the present paper we analyze recalibrated HAMO color cubes (spatial resolution ∼60 m/pixel) with a focus on dark material (DM). We present a definition of highly concentrated DM based on spectral parameters, subsequently map the DM across the Vestan surface, geologically classify DM, study its spectral properties on global and local scales, and finally, compare the FC in-flight color data with laboratory spectra. We have discovered an absorption band centered at 0.72 μm in localities of DM that show the lowest albedo values by using FC data as well as spectral information from Dawn’s imaging spectrometer VIR. Such localities are contained within impact-exposed outcrops on inner crater walls and ejecta material. Comparisons between spectral FC in-flight data, and laboratory spectra of meteorites and mineral mixtures in the wavelength range 0.4-1.0 μm, revealed that the absorption band can be attributed to the mineral serpentine, which is typically present in CM chondrites. Dark material in its purest form is rare on Vesta’s surface and is distributed globally in a non-uniform manner. Our findings confirm the hypothesis of an exogenic origin of the DM by the infall of carbonaceous chondritic material, likely of CM type. It further confirms the hypothesis that most of the DM was deposited by the Veneneia impact.

  16. Emerging functions of natural IgM and its Fc receptor FCMR in immune homeostasis

    Directory of Open Access Journals (Sweden)

    Hongsheng eWang

    2016-03-01

    Full Text Available Most natural IgM antibodies are encoded by germline Ig sequences and are produced in large quantities by both mice and humans in the absence of intentional immunization. Natural IgM are reactive with many conserved epitopes, including those shared by microorganisms and autoantigens. As a result, these antibodies play important roles in clearing intruding pathogens, as well as apoptotic/necrotic cells and otherwise damaged tissues. While natural IgM binds to target structures with low affinity due to a lack of significant selection by somatic hypermutation, its pentameric structure with 10 antigen binding sites enables these antibodies to bind multivalent target antigens with high avidity. Opsonization of antigen complexed with IgM is mediated by cell surface Fc receptors. While the existence of Fc alpha/mu receptor has been known for some time, only recently has the Fc receptor specific for IgM (FCMR been identified. In this review, we focus on our current understandings of how natural IgM and FCMR regulate the immune system and maintain homeostasis under physiological and pathological conditions.

  17. Activation-induced proteolysis of cytoplasmic domain of zeta in T cell receptors and Fc receptors.

    Science.gov (United States)

    Taupin, J L; Anderson, P

    1994-12-01

    The CD3-T cell receptor (TCR) complex on T cells and the Fc gamma receptor type III (Fc gamma RIII)-zeta-gamma complex on natural killer cells are functionally analogous activation receptors that associate with a family of disulfide-linked dimers composed of the related subunits zeta and gamma. Immunochemical analysis of receptor complexes separated on two-dimensional diagonal gels allowed the identification of a previously uncharacterized zeta-p14 heterodimer. zeta-p14 is a component of both CD3-TCR and Fc gamma RIII-zeta-gamma. Peptide mapping analysis shows that p14 is structurally related to zeta, suggesting that it is either: (i) derived from zeta proteolytically or (ii) the product of an alternatively spliced mRNA. The observation that COS cells transformed with a cDNA encoding zeta express zeta-p14 supports the former possibility. The expression of CD3-TCR complexes including zeta-p14 increases following activation with phorbol 12-myristate 13-acetate or concanavalin A, suggesting that proteolysis of zeta may contribute to receptor modulation or desensitization.

  18. Plant-expressed Fc-fusion protein tetravalent dengue vaccine with inherent adjuvant properties.

    Science.gov (United States)

    Kim, Mi Young; Copland, Alastair; Nayak, Kaustuv; Chandele, Anmol; Ahmed, Muhammad S; Zhang, Qibo; Diogo, Gil R; Paul, Matthew J; Hofmann, Sven; Yang, Moon-Sik; Jang, Yong-Suk; Ma, Julian K-C; Reljic, Rajko

    2017-12-09

    Dengue is a major global disease requiring improved treatment and prevention strategies. The recently licensed Sanofi Pasteur Dengvaxia vaccine does not protect children under the age of nine, and additional vaccine strategies are thus needed to halt this expanding global epidemic. Here, we employed a molecular engineering approach and plant expression to produce a humanized and highly immunogenic poly-immunoglobulin G scaffold (PIGS) fused to the consensus dengue envelope protein III domain (cEDIII). The immunogenicity of this IgG Fc receptor-targeted vaccine candidate was demonstrated in transgenic mice expressing human FcγRI/CD64, by induction of neutralizing antibodies and evidence of cell-mediated immunity. Furthermore, these molecules were able to prime immune cells from human adenoid/tonsillar tissue ex vivo as evidenced by antigen-specific CD4 + and CD8 + T-cell proliferation, IFN-γ and antibody production. The purified polymeric fraction of dengue PIGS (D-PIGS) induced stronger immune activation than the monomeric form, suggesting a more efficient interaction with the low-affinity Fcγ receptors on antigen-presenting cells. These results show that the plant-expressed D-PIGS have the potential for translation towards a safe and easily scalable single antigen-based tetravalent dengue vaccine. © 2017 The Authors. Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd.

  19. Effect of endogenous carotenoids on “adaptive” mutation in Escherichia coli FC40

    Science.gov (United States)

    Bridges, Bryn A.; Foster, Patricia L.; Timms, Andrew R.

    2010-01-01

    The appearance over many days of Lac+ frameshift mutations in Escherichia coli strain FC40 incubated on lactose selection plates is a classic example of apparent “adaptive” mutation in an episomal gene. We show that endogenously overproduced carotenoids reduce adaptive mutation under selective conditions by a factor of around two. Carotenoids are known to scavenge singlet oxygen suggesting that the accumulation of oxidative base damage may be an integral part of the adaptive mutation phenomenon. If so, the lesion cannot be 7,8-dihydro-8-oxoguanine since adaptive mutation in FC40 is unaffected by mutM and mutY mutations. If active oxygen species such as singlet oxygen are involved in adaptive mutation then they should also induce frameshift mutations in FC40 under non-selective conditions. We show that such mutations can be induced under non-selective conditions by protoporphyrin photosensitisation and that this photodynamic induction is reduced by a factor of just over two when endogenous carotenoids are present. We argue that the involvement of oxidative damage would in no way be inconsistent with current understanding of the mechanism of adaptive mutation and the role of DNA polymerases. PMID:11166030

  20. Macrophage colony stimulating factor (M-CSF) induces Fc receptor expression on macrophages

    International Nuclear Information System (INIS)

    Magee, D.M.; Wing, E.J.; Waheed, A.; Shadduck, R.K.

    1986-01-01

    M-CSF is a glycoprotein that stimulates bone marrow progenitor cells to proliferate and differentiate into macrophages (M theta). In addition, M-CSF can modulate the function of mature M theta. In this study, the authors determined the effect of M-CSF on expression of receptors for IgG (Fc receptors). Murine resident peritoneal M theta monolayers were incubated with either M-CSF, recombinant gamma interferon (IFN), or left untreated for 48 hrs. Expression of Fc receptors was assessed by microscopy using an antibody coated sheet erythrocytes (EA) rosette assay. The results indicated that M-CSF treated M theta had significantly higher numbers of bound EA (7.1 erythrocytes/M theta), than IFN M theta (4.4), or untreated M theta (2.5) (p 51 Cr labelled EA assay, CSF M theta (16,411 cpm), IFN M theta (10,887), untreated M theta (6897) (p < 0.001). Additionally, the maximal response was noted between 10 and 500 units M-CSF. Purified anti-M-CSF IgG, when included in the cultures, ablated the enhancement of EA binding, whereas normal rabbit IgG did not. These findings indicate that M-CSF is a potent inducer of Fc receptor expression on M theta and supports other data concerning the role of M-CSF as a biological response modifier

  1. Inhibition of Notch signaling by Dll4-Fc promotes reperfusion of acutely ischemic tissues

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Ren [Department of Pathology, University of Southern California, Los Angeles (United States); Trindade, Alexandre [Centro Interdisciplinar de Investigacao em Sanidade Animal (CIISA), Lisbon Technical University, Lisbon (Portugal); Instituto Gulbenkian de Ciencia, Oeiras (Portugal); Sun, Zhanfeng [Department of Vascular Surgery, 2nd Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang (China); Kumar, Ram; Weaver, Fred A. [Department of Surgery, University of Southern California, Los Angeles (United States); Krasnoperov, Valery; Naga, Kranthi [Vasgene Therapeutics, Los Angeles, CA (United States); Duarte, Antonio [Centro Interdisciplinar de Investigacao em Sanidade Animal (CIISA), Lisbon Technical University, Lisbon (Portugal); Instituto Gulbenkian de Ciencia, Oeiras (Portugal); Gill, Parkash S., E-mail: parkashg@usc.edu [Department of Pathology, University of Southern California, Los Angeles (United States)

    2012-02-03

    Highlights: Black-Right-Pointing-Pointer Low dose Dll4-Fc increases vascular proliferation and overall perfusion. Black-Right-Pointing-Pointer Low dose Dll4-Fc helps vascular injury recovery in hindlimb ischemia model. Black-Right-Pointing-Pointer Low dose Dll4-Fc helps vascular injury recovery in skin flap model. Black-Right-Pointing-Pointer Dll4 heterozygous deletion promotes vascular injury recovery. Black-Right-Pointing-Pointer Dll4 overexpression delays vascular injury recovery. -- Abstract: Notch pathway regulates vessel development and maturation. Dll4, a high-affinity ligand for Notch, is expressed predominantly in the arterial endothelium and is induced by hypoxia among other factors. Inhibition of Dll4 has paradoxical effects of reducing the maturation and perfusion in newly forming vessels while increasing the density of vessels. We hypothesized that partial and/or intermittent inhibition of Dll4 may lead to increased vascular response and still allow vascular maturation to occur. Thus tissue perfusion can be restored rapidly, allowing quicker recovery from ischemia or tissue injury. Our studies in two different models (hindlimb ischemia and skin flap) show that inhibition of Dll4 at low dose allows faster recovery from vascular and tissue injury. This opens a new possibility for Dll4 blockade's therapeutic application in promoting recovery from vascular injury and restoring blood supply to ischemic tissues.

  2. Strongyloides ratti: implication of mast cell-mediated expulsion through FcεRI-independent mechanisms

    Directory of Open Access Journals (Sweden)

    Watanabe K.

    2009-09-01

    Full Text Available In order to examine whether FcεRI-dependent degranulation of intestinal mast cells is required for expulsion of intestinal nematode Strongyloides ratti, CD45 exon6-deficient (CD45-/- mice were inoculated with S. ratti. In CD45-/- mice, egg excretion in feces persisted for more than 30 days following S. ratti larvae inoculation, whereas in wild-type (CD45+/+ mice, the eggs completely disappeared by day 20 post-infection. The number of intestinal mucosal mast cells, which are known effector cells for the expulsion of S. ratti, was 75% lower in CD45-/- mice compared with that in CD45+/+ mice. Adoptive transfer of wild-type T cells from CD45+/+ mice into CD45-/- mice reduced the duration of S. ratti infection to comparable levels observed in CD45+/+ mice, with concomitant increases in intestinal mucosal mast cells. These results showed that CD45 is not involved in the effector function of intestinal mucosal mast cells against S. ratti infection. Since FcεRI-dependent degranulation of mast cells is completely impaired in these CD45 knockout mice, we conclude that FcεRIdependent degranulation is not required in the protective function of intestinal mucosal mast cells against primary infection of S. ratti.

  3. Flux rope breaking and formation of a rotating blowout jet

    Science.gov (United States)

    Joshi, Navin Chandra; Nishizuka, Naoto; Filippov, Boris; Magara, Tetsuya; Tlatov, Andrey G.

    2018-05-01

    We analysed a small flux rope eruption converted into a helical blowout jet in a fan-spine configuration using multiwavelength observations taken by Solar Dynamics Observatory, which occurred near the limb on 2016 January 9. In our study, first, we estimated the fan-spine magnetic configuration with the potential-field calculation and found a sinistral small filament inside it. The filament along with the flux rope erupted upwards and interacted with the surrounding fan-spine magnetic configuration, where the flux rope breaks in the middle section. We observed compact brightening, flare ribbons, and post-flare loops underneath the erupting filament. The northern section of the flux rope reconnected with the surrounding positive polarity, while the southern section straightened. Next, we observed the untwisting motion of the southern leg, which was transformed into a rotating helical blowout jet. The sign of the helicity of the mini-filament matches the one of the rotating jets. This is consistent with recent jet models presented by Adams et al. and Sterling et al. We focused on the fine thread structure of the rotating jet and traced three blobs with the speed of 60-120 km s- 1, while the radial speed of the jet is ˜400 km s- 1. The untwisting motion of the jet accelerated plasma upwards along the collimated outer spine field lines, and it finally evolved into a narrow coronal mass ejection at the height of ˜9Rsun. On the basis of detailed analysis, we discussed clear evidence of the scenario of the breaking of the flux rope and the formation of the helical blowout jet in the fan-spine magnetic configuration.

  4. Compact neutron flux monitor

    International Nuclear Information System (INIS)

    Madhavi, V.; Phatak, P.R.; Bahadur, C.; Bayala, A.K.; Jakati, R.K.; Sathian, V.

    2003-01-01

    Full text: A compact size neutron flux monitor has been developed incorporating standard boards developed for smart radiation monitors. The sensitivity of the monitors is 0.4cps/nV. It has been tested up to 2075 nV flux with standard neutron sources. It shows convincing results even in high flux areas like 6m away from the accelerator in RMC (Parel) for 106/107 nV. These monitors have a focal and remote display, alarm function with potential free contacts for centralized control and additional provision of connectivity via RS485/Ethernet. This paper describes the construction, working and results of the above flux monitor

  5. High-speed and supersonic upward plasma drifts: multi-instrumental study

    Science.gov (United States)

    Astafyeva, E.; Zakharenkova, I.; Hairston, M. R.; Huba, J.; Coley, W. R.

    2017-12-01

    Since the pioneering observations by Aggson et al. (1992, JGR, doi: 10.1002/92JA00644), there have been several reports of the occurrence of high-speed (Vz>800 m/s) and supersonic plasma flows in the post-sunset (e.g., Hysell et al., 1994, JGR, doi: 10.1029/94JA00476; Hanson et al., 1997, JGR, doi: 10.1029/96JA03376) and the pre-dawn sector (Astafyeva and Zakharenkova, 2015, GRL, doi:10.1002/2015GL066369). However, despite this observational evidence, these events remain rare and are not well understood. The main issue is to determine the background conditions leading to the occurrence of these high-speed plasma drifts. In this work, we perform a multi-instrumental study of high-speed and supersonic upward plasma drift events/structures. For this purpose, we analyze data from several ground-based and space-borne instruments, including data from the DMSP, Swarm and C/NOFS (IVM instrument) satellites. In addition to the space-borne instruments, we use data from ground-based GPS-receivers and ionosondes to further investigate the background ionosphere conditions, as well as the effects produced by the plasma bubbles and ionospheric irregularities. Besides the observations, we add the SAMI3/ESF modeling results on plasma bubble simulations and high-speed drifts inside plasma bubbles. TIE-GCM runs (from the CCMC, https://ccmc.gsfc.nasa.gov) are used to define the background atmospheric/ionospheric and electrodynamical conditions leading to the occurrence of the high-speed and supersonic plasma drift events. Our search of events with upward plasma drift exceeding 800 m/s in the data of DMSP for the years 2002-2016 shows that such high-speed events are extremely rare. During this period of time, only 6 events were found, two of them occurred during the recovery phase of a geomagnetic storm, while the other four were detected during geomagnetically quiet conditions. Concerning the generation of such events, our preliminary results show that enhanced electric fields are

  6. How does the architecture of a fault system controls magma upward migration through the crust?

    Science.gov (United States)

    Iturrieta, P. C.; Cembrano, J. M.; Stanton-Yonge, A.; Hurtado, D.

    2017-12-01

    The orientation and relative disposition of adjacent faults locally disrupt the regional stress field, thus enhancing magma flow through previous or newly created favorable conduits. Moreover, the brittle-plastic transition (BPT), due to its stronger rheology, governs the average state of stress of shallower portions of the fault system. Furthermore, the BPT may coincide with the location of transient magma reservoirs, from which dikes can propagate upwards into the upper crust, shaping the inner structure of the volcanic arc. In this work, we examine the stress distribution in strike-slip duplexes with variable geometry, along with the critical fluid overpressure ratio (CFOP), which is the minimum value required for individual faults to fracture in tension. We also determine the stress state disruption of the fault system when a dike is emplaced, to answer open questions such as: what is the nature of favorable pathways for magma to migrate? what is the architecture influence on the feedback between fault system kinematics and magma injection? To this end, we present a 3D coupled hydro-mechanical finite element model of the continental lithosphere, where faults are represented as continuum volumes with an elastic-plastic rheology. Magma flow upon fracturing is modeled through non-linear Stoke's flow, coupling solid and fluid equilibrium. A non-linear sensitivity analysis is performed in function of tectonic, rheology and geometry inputs, to assess which are the first-order factors that governs the nature of dike emplacement. Results show that the CFOP is heterogeneously distributed in the fault system, and within individual fault segments. Minimum values are displayed near fault intersections, where local kinematics superimpose on regional tectonic loading. Furthermore, when magma is transported through a fault segment, the CFOP is now minimized in faults with non-favorable orientations. This suggests that these faults act as transient pathways for magma to

  7. Mouse splenic and bone marrow cell populations that express high-affinity Fc epsilon receptors and produce interleukin 4 are highly enriched in basophils.

    OpenAIRE

    Seder, R A; Paul, W E; Dvorak, A M; Sharkis, S J; Kagey-Sobotka, A; Niv, Y; Finkelman, F D; Barbieri, S A; Galli, S J; Plaut, M

    1991-01-01

    Splenic and bone marrow cells from normal mice, and from mice that have been polyclonally activated by injection of anti-IgD antibody, contain cells that produce interleukin 4 (IL-4) in response to crosslinkage of Fc epsilon receptors (Fc epsilon R) or Fc gamma R or to ionomycin. Isolated Fc epsilon R+ cells have recently been shown to contain all of the IL-4-producing capacity of the nonlymphoid compartment of spleen and bone marrow. Here, purified Fc epsilon R+ cells are shown to be enriche...

  8. Flux structures in mesoscopic Y Ba2Cu3O7-δ discs

    International Nuclear Information System (INIS)

    Crisan, A; Bending, S J; Pross, A; Aziz, A; Grigorenko, A N; Humphreys, R G

    2005-01-01

    Scanning Hall probe microscopy has been used to study flux structures and dynamics in 5 μm x 5 μm YBCO thin film squares, which are mesoscopic with respect to the magnetic penetration depth, λ(T), at temperatures close to T c . A number of unusual vortex phenomena are observed in these microstructures which differ qualitatively from the expected behaviour of more macroscopic pieces of film. In field-cooled (FC) experiments to ∼65K a full Meissner state is generated for cooling fields less than ∼6 Oe, reflecting the relatively small demagnetization factors in our samples. Cooling in higher fields, however, results in only a very weak diamagnetic response at low temperatures whose magnitude is almost independent of the cooling field. In contrast we observe considerable trapped flux upon field-removal whose magnitude grows monotonically with cooling field. Remarkably, all FC flux distributions exhibit almost perfect rotational symmetry, and can be nearly completely cancelled in a reversible fashion by tuning the field applied to the initially FC state. Our field-cooled and zero-field-cooled results have been analysed in terms of a Bean-like critical state model containing constant edge and bulk current densities, and most of the observed phenomena can be explained by considering the relative weight of these two components. Not all flux profiles can be described by our simple model, however, and under certain circumstances symmetry-breaking 'dipole'-like flux structures can form in several adjacent YBCO squares. We speculate that these are related to the unidirectional Ar ion milling process which was used to pattern the squares and could have broken the expected four-fold symmetry. We note that our results could have important implications for the miniaturization of thin film HTS devices

  9. Magnetic reconnection during eruptive magnetic flux ropes

    Science.gov (United States)

    Mei, Z. X.; Keppens, R.; Roussev, I. I.; Lin, J.

    2017-08-01

    Aims: We perform a three-dimensional (3D) high resolution numerical simulation in isothermal magnetohydrodynamics to study the magnetic reconnection process in a current sheet (CS) formed during an eruption of a twisted magnetic flux rope (MFR). Because the twist distribution violates the Kruskal-Shafranov condition, the kink instability occurs, and the MFR is distorted. The centre part of the MFR loses its equilibrium and erupts upward, which leads to the formation of a 3D CS underneath it. Methods: In order to study the magnetic reconnection inside the CS in detail, mesh refinement has been used to reduce the numerical diffusion and we estimate a Lundquist number S = 104 in the vicinity of the CS. Results: The refined mesh allows us to resolve fine structures inside the 3D CS: a bifurcating sheet structure signaling the 3D generalization of Petschek slow shocks, some distorted-cylindrical substructures due to the tearing mode instabilities, and two turbulence regions near the upper and the lower tips of the CS. The topological characteristics of the MFR depend sensitively on the observer's viewing angle: it presents as a sigmoid structure, an outwardly expanding MFR with helical distortion, or a flare-CS-coronal mass ejection symbiosis as in 2D flux-rope models when observed from the top, the front, or the side. The movie associated to Fig. 2 is available at http://www.aanda.org

  10. Surface tension effects on vertical upward annular flows in a small diameter pipe

    Energy Technology Data Exchange (ETDEWEB)

    Sadatomi, Michio, E-mail: sadatomi@mech.kumamoto-u.ac.jp [Dept. of Advanced Mechanical Systems, Kumamoto Univ., 39-1, Kurokami 2-chome, Chuou-ku, Kumamoto 860-8555 (Japan); Kawahara, Akimaro [Dept. of Advanced Mechanical Systems, Kumamoto Univ., 39-1, Kurokami 2-chome, Chuou-ku, Kumamoto 860-8555 (Japan); Suzuki, Aruta [Plant Design & Engineering Dept., Environment, Energy & Plant Headquarters, Hitachi Zosen Corporation, 7-89, Nankokita 1-chome, Suminoe-ku, Osaka, 559-8559 (Japan)

    2016-12-15

    Highlights: • Surface tension effects were clarified on annular flow in a small diameter pipe. • The mean liquid film thickness became thinner with decreasing of surface tension. • The liquid droplet fraction and the interfacial shear stress became higher with it. • New prediction methods for the above parameters were developed and validated. - Abstract: Experiments were conducted to study the surface tension effects on vertical upward annular flows in a 5 mm I.D. pipe using water and low surface tension water with a little surfactant as the test liquid and air as the test gas. Firstly, the experimental results on the mean liquid film thickness, the liquid droplet fraction and the interfacial shear stress in annular flows together with some flow pictures are presented to clarify the surface tension effects. From these, the followings are clarified: In the low surface tension case, the liquid film surface becomes rough, the liquid film thickness thin, the liquid droplet fraction high, and the interfacial shear stress high. Secondary, correlations in literatures for the respective parameters are tested against the present data. The test results show that no correlation for the respective parameters could predict well the present data. Thus, correlations are revised by accounting for the surface tension effects. The results of the experiments, the correlations tests and their revisions mentioned above are presented in the present paper.

  11. Global change and upward shift of treeline in the Alps: genetic consequences of pastures colonization

    Directory of Open Access Journals (Sweden)

    Piotti A

    2007-01-01

    Full Text Available In the Alps global warming and change in land use, in particular the drastic reduction in cattle grazing, are causing a progressive treeline ecotone upwards shift. The colonization dynamics of woody species are modulated by high selective pressure on seedlings due to the extreme ecological conditions of this habitat. We studied the colonization dynamics of Norway spruce in a treeline plot, at the upper limit of the Paneveggio forest (Trentino, Italy. We have exhaustively sampled the study stand, collecting needle tissue from all the adults and the juveniles detected, and we have genotyped all the samples (376 with 4 SSR markers. Parentage relationships between the few adults presents in the stand (23 and the juveniles were established. Our results indicate that, in spite of extreme ecological condition of the treeline environment, local adaptations do not seem to favour local parents: only 4% of juveniles have both parents among local adult trees, while 96% of juveniles are completely or partially sired outside the sampling area. Assessing parentage relationship also allowed the estimation of relative reproductive success of local adult trees. Out of a total of 23 adult trees, 5 trees were involved in the 59% of successful reproductive events detected inside the sampling area.

  12. On the One-Dimensional Modeling of Vertical Upward Bubbly Flow

    Directory of Open Access Journals (Sweden)

    C. Peña-Monferrer

    2018-01-01

    Full Text Available The one-dimensional two-fluid model approach has been traditionally used in thermal-hydraulics codes for the analysis of transients and accidents in water–cooled nuclear power plants. This paper investigates the performance of RELAP5/MOD3 predicting vertical upward bubbly flow at low velocity conditions. For bubbly flow and vertical pipes, this code applies the drift-velocity approach, showing important discrepancies with the experiments compared. Then, we use a classical formulation of the drag coefficient approach to evaluate the performance of both approaches. This is based on the critical Weber criteria and includes several assumptions for the calculation of the interfacial area and bubble size that are evaluated in this work. A more accurate drag coefficient approach is proposed and implemented in RELAP5/MOD3. Instead of using the Weber criteria, the bubble size distribution is directly considered. This allows the calculation of the interfacial area directly from the definition of Sauter mean diameter of a distribution. The results show that only the proposed approach was able to predict all the flow characteristics, in particular the bubble size and interfacial area concentration. Finally, the computational results are analyzed and validated with cross-section area average measurements of void fraction, dispersed phase velocity, bubble size, and interfacial area concentration.

  13. Sea ice draft in the Weddell Sea, measured by upward looking sonars

    Directory of Open Access Journals (Sweden)

    A. Behrendt

    2013-06-01

    Full Text Available The presented database contains time-referenced sea ice draft values from upward looking sonar (ULS measurements in the Weddell Sea, Antarctica. The sea ice draft data can be used to infer the thickness of the ice. They were collected during the period 1990–2008. In total, the database includes measurements from 13 locations in the Weddell Sea and was generated from more than 3.7 million measurements of sea ice draft. The files contain uncorrected raw drafts, corrected drafts and the basic parameters measured by the ULS. The measurement principle, the data processing procedure and the quality control are described in detail. To account for the unknown speed of sound in the water column above the ULS, two correction methods were applied to the draft data. The first method is based on defining a reference level from the identification of open water leads. The second method uses a model of sound speed in the oceanic mixed layer and is applied to ice draft in austral winter. Both methods are discussed and their accuracy is estimated. Finally, selected results of the processing are presented. The data can be downloaded from doi:10.1594/PANGAEA.785565.

  14. Theory and observations of upward field-aligned currents at the magnetopause boundary layer.

    Science.gov (United States)

    Wing, Simon; Johnson, Jay R

    2015-11-16

    The dependence of the upward field-aligned current density ( J ‖ ) at the dayside magnetopause boundary layer is well described by a simple analytic model based on a velocity shear generator. A previous observational survey confirmed that the scaling properties predicted by the analytical model are applicable between 11 and 17 MLT. We utilize the analytic model to predict field-aligned currents using solar wind and ionospheric parameters and compare with direct observations. The calculated and observed parallel currents are in excellent agreement, suggesting that the model may be useful to infer boundary layer structures. However, near noon, where velocity shear is small, the kinetic pressure gradients and thermal currents, which are not included in the model, could make a small but significant contribution to J ‖ . Excluding data from noon, our least squares fit returns log( J ‖,max_cal ) = (0.96 ± 0.04) log( J ‖_obs ) + (0.03 ± 0.01) where J ‖,max_cal = calculated J ‖,max and J ‖_obs = observed J ‖ .

  15. The Fc Receptor Polymorphisms and Expression of Neutrophil Activation Markers in Patients with Sickle Cell Disease from Western India

    Directory of Open Access Journals (Sweden)

    Harshada K. Kangne

    2013-01-01

    Full Text Available Objective. Sickle cell disease has variable clinical manifestations. Activation of neutrophils plays an important role in the initiation and propagation of vaso occlusive crises which can be analysed by determining the expression of neutrophil antigens such as CD16, CD32, and CD62L. The common FcγR polymorphisms (FcγRIIA and FcγRIIIB are considered to influence clinical presentation. This study focuses on distribution of FcγR polymorphisms and their association with neutrophil activity among the patients from western India. Methods. In this paper 127 sickle cell anemia patients and 58 patients with sickle-β-thalassemia (median age 12±8.58 years with variable clinical phenotypes along with 175 normals were investigated. FcγRs polymorphisms were analysed by RFLP and AS-PCR. Activation of neutrophils was measured by flow cytometry. Results. The genotypic frequency of the H/R genotype of FcγRIIA and the NA1/NA1 genotype of FcγRIIIB was significantly decreased in patients compared to normals (P-0.0074, P-0.0471, resp.. We found a significant difference in the expression of CD32 and CD62L among the patients as against normals. A significantly higher expression of CD32 was seen in the milder patients with the H/H genotype (P-0.0231, whereas the expression of CD16 was higher in severe patients with the NA2/NA2 genotype (P-0.0312. Conclusion. The two FcγR polymorphisms had significant association with variable phenotypes of sickle cell disease. The expression of CD62L decreased in our patients indicating activation of neutrophils.

  16. Site-selective conjugation of an anticoagulant aptamer to recombinant albumins and maintenance of neonatal Fc receptor binding

    Science.gov (United States)

    Schmøkel, Julie; Voldum, Anders; Tsakiridou, Georgia; Kuhlmann, Matthias; Cameron, Jason; Sørensen, Esben S.; Wengel, Jesper; Howard, Kenneth A.

    2017-05-01

    Aptamers are an attractive molecular medicine that offers high target specificity. Nucleic acid-based aptamers, however, are prone to nuclease degradation and rapid renal excretion that require blood circulatory half-life extension enabling technologies. The long circulatory half-life, predominately facilitated by engagement with the cellular recycling neonatal Fc receptor (FcRn), and ligand transport properties of albumin promote it as an attractive candidate to improve the pharmacokinetic profile of aptamers. This study investigates the effect of Cys34 site-selective covalent attachment of a factor IXa anticoagulant aptamer on aptamer functionality and human FcRn (hFcRn) engagement using recombinant human albumin (rHA) of either a wild type (WT) or an engineered human FcRn high binding variant (HB). Albumin-aptamer conjugates, connected covalently through a heterobifunctional succinimidyl 4-(N-maleimidomethyl)cyclohexane-1-carboxylate linker, were successfully prepared and purified by high performance liquid chromatography as confirmed by gel electrophoresis band-shift analysis and matrix-assisted laser desorption/ionization time of flight. Minimal reduction (∼25%) in activity of WT-linked aptamer to that of aptamer alone was found using an anticoagulant activity assay measuring temporal levels of activated partial thrombin. Covalent albumin-aptamer conjugation, however, substantially compromized binding to hFcRn, to 10% affinity of that of non-conjugated WT, determined by biolayer interferometry. Binding could be rescued by aptamer conjugation to recombinant albumin engineered for higher FcRn affinity (HB) that exhibited an 8-fold affinity compared to WT alone. This work describes a novel albumin-based aptamer delivery system whose hFcRn binding can be increased using a HB engineered albumin.

  17. Fabrication of GNPs/CDSH-Fc/nafion modified electrode for the detection of dopamine in the presence of ascorbic acid

    International Nuclear Information System (INIS)

    Chen Ming; Wei Xiujuan; Qian Hui; Diao Guowang

    2011-01-01

    A novel dopamine sensor was fabricated by forming the inclusion complex between mono-6-thio-β-cyclodextrin (CD-SH) and ferrocene (Fc) functionalized gold nanoparticles (GNPs) films on a platinum electrode. The properties of the GNPs/CDSH-Fc nanocomposite were characterized by Fourier transform infrared spectra, UV-visible absorption spectroscopy, transmission electron microscopy and cyclic voltammetry. The electrochemistry of dopamine (DA) was investigated by cyclic voltammetry (CV) and differential pulse voltammograms (DPV). The electrooxidation of dopamine could be catalyzed by Fc/Fc + couple as a mediator and had a higher electrochemical response due to the unique performance of GNPs/CDSH-Fc. The anodic peaks of DA and ascorbic acid (AA) in their mixture can be well separated by the prepared electrode. Under optimum conditions linear calibration graphs were obtained over the DA concentration range 2.0 x 10 -6 to 5.0 x 10 -5 M with a correlation coefficient of 0.998 and a detection limit of 9.0 x 10 -8 M (S/N = 3). The modified electrode had been effectively applied for the assay of DA in dopamine hydrochloride injections. This work provides a simple and easy approach to selectively detect DA in the presence of AA. - Research highlights: → The sensor of DA was constructed by using GNPs/CDSH-Fc as the building block. → Inclusion complex on the surface of GNPs decreased the leakage of mediator. → The electro-oxidation of DA could be catalyzed by Fc/Fc + couple as a mediator. → This work provides a simple approach to selectively detect DA in the presence of AA.

  18. Primary cosmic ray flux

    Energy Technology Data Exchange (ETDEWEB)

    Stanev, Todor

    2001-05-01

    We discuss the primary cosmic ray flux from the point of view of particle interactions and production of atmospheric neutrinos. The overall normalization of the cosmic ray flux and its time variations and site dependence are major ingredients of the atmospheric neutrino predictions and the basis for the derivation of the neutrino oscillation parameters.

  19. Flux cutting in superconductors

    International Nuclear Information System (INIS)

    Campbell, A M

    2011-01-01

    This paper describes experiments and theories of flux cutting in superconductors. The use of the flux line picture in free space is discussed. In superconductors cutting can either be by means of flux at an angle to other layers of flux, as in longitudinal current experiments, or due to shearing of the vortex lattice as in grain boundaries in YBCO. Experiments on longitudinal currents can be interpreted in terms of flux rings penetrating axial lines. More physical models of flux cutting are discussed but all predict much larger flux cutting forces than are observed. Also, cutting is occurring at angles between vortices of about one millidegree which is hard to explain. The double critical state model and its developments are discussed in relation to experiments on crossed and rotating fields. A new experiment suggested by Clem gives more direct information. It shows that an elliptical yield surface of the critical state works well, but none of the theoretical proposals for determining the direction of E are universally applicable. It appears that, as soon as any flux flow takes place, cutting also occurs. The conclusion is that new theories are required. (perspective)

  20. Void fraction development in gas-liquid flow after a U-bend in a vertically upwards serpentine-configuration large-diameter pipe

    Science.gov (United States)

    Almabrok, Almabrok A.; Aliyu, Aliyu M.; Baba, Yahaya D.; Lao, Liyun; Yeung, Hoi

    2018-01-01

    We investigate the effect of a return U-bend on flow behaviour in the vertical upward section of a large-diameter pipe. A wire mesh sensor was employed to study the void fraction distributions at axial distances of 5, 28 and 47 pipe diameters after the upstream bottom bend. The study found that, the bottom bend has considerable impacts on up-flow behaviour. In all conditions, centrifugal action causes appreciable misdistribution in the adjacent straight section. Plots from WMS measurements show that flow asymmetry significantly reduces along the axis at L/D = 47. Regime maps generated from three axial locations showed that, in addition to bubbly, intermittent and annular flows, oscillatory flow occurred particularly when gas and liquid flow rates were relatively low. At this position, mean void fractions were in agreement with those from other large-pipe studies, and comparisons were made with existing void fraction correlations. Among the correlations surveyed, drift flux-type correlations were found to give the best predictive results.

  1. Anti-coagulation effect of Fc fragment against anti-β2-GP1 antibodies in mouse models with APS.

    Science.gov (United States)

    Xie, Weidong; Zhang, Yaou; Bu, Cunya; Sun, Shijing; Hu, Shaoliang; Cai, Guoping

    2011-01-01

    Anti-beta (2)-glycoprotein I (anti-β2-GP1) is one of the important pathogenesis factors responsible for thrombosis formation in patients with antiphospholipid syndrome (APS). Administration of intravenous immunoglobulin (IVIg) is a common method used to inhibit the abnormal antibody levels and decrease the mortality of APS in emergency situations. We hypothesize that the Fc fragment of IgG is the molecular structure responsible for these effects. The present study investigates the beneficial effects of both recombinant and natural human Fc fragments of heterogeneous IgG against human anti-β2-GP1 antibodies in mouse models with APS. Results showed that both recombinant and natural human Fc fragments moderately but significantly decreased the levels of serum anti-β2-GP1 antibodies and had anti-coagulation effects in human β2-GP1-immunized mice. Furthermore, both recombinant and natural human Fc fragments inhibited thrombosis formation and decreased mortality in mouse models infused intravenously with human anti-β2GP1 antibodies from patients with APS. Findings suggest that the Fc fragment might be one of the active structural units of heterogeneous IgG. Thus, recombinant human Fc fragment administration may be a useful treatment for individuals with APS. Copyright © 2010 Elsevier B.V. All rights reserved.

  2. Heat flux microsensor measurements

    Science.gov (United States)

    Terrell, J. P.; Hager, J. M.; Onishi, S.; Diller, T. E.

    1992-01-01

    A thin-film heat flux sensor has been fabricated on a stainless steel substrate. The thermocouple elements of the heat flux sensor were nickel and nichrome, and the temperature resistance sensor was platinum. The completed heat flux microsensor was calibrated at the AEDC radiation facility. The gage output was linear with heat flux with no apparent temperature effect on sensitivity. The gage was used for heat flux measurements at the NASA Langley Vitiated Air Test Facility. Vitiated air was expanded to Mach 3.0 and hydrogen fuel was injected. Measurements were made on the wall of a diverging duct downstream of the injector during all stages of the hydrogen combustion tests. Because the wall and the gage were not actively cooled, the wall temperature reached over 1000 C (1900 F) during the most severe test.

  3. Preliminary limits on the flux of muon neutrinos from extraterrestrial point sources

    International Nuclear Information System (INIS)

    Bionta, R.M.; Blewitt, G.; Bratton, C.B.

    1985-01-01

    We present the arrival directions of 117 upward-going muon events collected with the IMB proton lifetime detector during 317 days of live detector operation. The rate of upward-going muons observed in our detector was found to be consistent with the rate expected from atmospheric neutrino production. The upper limit on the total flux of extraterrestrial neutrinos >1 GeV is 2 -sec. Using our data and a Monte Carlo simulation of high energy muon production in the earth surrounding the detector, we place limits on the flux of neutrinos from a point source in the Vela X-2 system of 2 -sec with E > 1 GeV. 6 refs., 5 figs

  4. Ethnic diversity and social capital in upward mobility systems: Problematizing the permeability of intra-organizational career boundaries

    NARCIS (Netherlands)

    Ossenkop, C.; Vinkenburg, C.J.; Jansen, P.G.W.; Ghorashi, H.

    2015-01-01

    Purpose – The purpose of this paper is to contribute to a better understanding of the complex relationship between ethnic diversity, social capital, and objective career success in upward mobility systems over time. The authors conceptualize the underlying process of why intra-organizational career

  5. Education as Literacy for Freedom: Implications for Latin America and the Caribbean from an Upward Bound Project.

    Science.gov (United States)

    Dottin, Erskine S.

    The Upward Bound Project for low income youth in Florida emphasizes humanistic education rather than education based on the capitalistic model of production, consumption, and competition. The project, which can serve as a model for education in developing countries, focuses on creating self-concepts and values to counteract those of an acquisitive…

  6. Mindfulness training promotes upward spirals of positive affect and cognition : Multilevel and autoregressive latent trajectory modeling analyses

    NARCIS (Netherlands)

    Garland, Eric L.; Geschwind, Nicole; Peeters, Frenk; Wichers, Marieke

    2015-01-01

    Recent theory suggests that positive psychological processes integral to health may be energized through the self-reinforcing dynamics of an upward spiral to counter emotion dysregulation. The present study examined positive emotion-cognition interactions among individuals in partial remission from

  7. Upward continuation of Dome-C airborne gravity and comparison with GOCE gradients at orbit altitude in east Antarctica

    DEFF Research Database (Denmark)

    Yildiz, Hasan; Forsberg, René; Tscherning, Carl Christian

    2017-01-01

    spherical harmonic models confirmed the quality of the airborne data and that they contain more high-frequency signal than the global models. First, the airborne gravity data were upward continued to GOCE altitude to predict gravity gradients in the local North-East-Up reference frame. In this step...

  8. Heat Transfer Experiment with Supercritical CO{sub 2} Flowing Upward in a Circular Tube

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Hyung Rae; Kim, Hwan Yeol; Song, Jin Ho; Kim, Hee Dong; Bae, Yoon Yeong [Korea Atomic Energy Research Institute, Taejon (Korea, Republic of)

    2005-07-01

    SCWR (SuperCritical Water-cooled Reactor) is one of the six reactor candidates selected in the Gen-IV project, which aims at the development of new reactors with enhanced economy and safety. Heat transfer experiments under supercritical conditions are required in relevant geometries for the proper prediction of thermo-hydraulic phenomena in a reactor core. A heat transfer test loop, named as SPHINX (Supercritical Pressure Heat Transfer Investigation for NeXt generation), has been constructed in KAERI. The loop uses carbon dioxide as a surrogate fluid for water since the critical pressure and temperature of CO{sub 2} are much lower those of water. As a first stage of heat transfer experiments, a single tube test is being performed in the test loop. Controlled parameters for the tests are operating pressure, mass flux, and heat flux. Wall temperatures are measured along the tube. Experimental data are compared with existing correlations.

  9. Heat Transfer Experiment with Supercritical CO2 Flowing Upward in a Circular Tube

    International Nuclear Information System (INIS)

    Kim, Hyung Rae; Kim, Hwan Yeol; Song, Jin Ho; Kim, Hee Dong; Bae, Yoon Yeong

    2005-01-01

    SCWR (SuperCritical Water-cooled Reactor) is one of the six reactor candidates selected in the Gen-IV project, which aims at the development of new reactors with enhanced economy and safety. Heat transfer experiments under supercritical conditions are required in relevant geometries for the proper prediction of thermo-hydraulic phenomena in a reactor core. A heat transfer test loop, named as SPHINX (Supercritical Pressure Heat Transfer Investigation for NeXt generation), has been constructed in KAERI. The loop uses carbon dioxide as a surrogate fluid for water since the critical pressure and temperature of CO 2 are much lower those of water. As a first stage of heat transfer experiments, a single tube test is being performed in the test loop. Controlled parameters for the tests are operating pressure, mass flux, and heat flux. Wall temperatures are measured along the tube. Experimental data are compared with existing correlations

  10. FcγRII-binding Centyrins mediate agonism and antibody-dependent cellular phagocytosis when fused to an anti-OX40 antibody.

    Science.gov (United States)

    Zhang, Di; Whitaker, Brian; Derebe, Mehabaw G; Chiu, Mark L

    2018-04-01

    Immunostimulatory antibodies against the tumor necrosis factor receptors (TNFR) are emerging as promising cancer immunotherapies. The agonism activity of such antibodies depends on crosslinking to Fc gamma RIIB receptor (FcγRIIB) to enable the antibody multimerization that drives TNFR activation. Previously, Fc engineering was used to enhance the binding of such antibodies to Fcγ receptors. Here, we report the identification of Centyrins as alternative scaffold proteins with binding affinities to homologous FcγRIIB and FcγRIIA, but not to other types of Fcγ receptors. One Centyrin, S29, was engineered at distinct positions of an anti-OX40 SF2 antibody to generate bispecific and tetravalent molecules named as mAbtyrins. Regardless of the position of S29 on the SF2 antibody, SF2-S29 mAbtyrins could bind FcγRIIB and FcγRIIA specifically while maintaining binding to OX40 receptors. In a NFκB reporter assay, attachment of S29 Centyrin molecules at the C-termini, but not the N-termini, resulted in SF2 antibodies with increased agonism owing to FcγRIIB crosslinking. The mAbtyrins also showed agonism in T-cell activation assays with immobilized FcγRIIB and FcγRIIA, but this activity was confined to mAbtyrins with S29 specifically at the C-termini of antibody heavy chains. Furthermore, regardless of the position of the molecule, S29 Centyrin could equip an otherwise Fc-silent antibody with antibody-dependent cellular phagocytosis activity without affecting the antibody's intrinsic antibody-dependent cell-meditated cytotoxicity and complement-dependent cytotoxicity. In summary, the appropriate adoption FcγRII-binding Centyrins as functional modules represents a novel strategy to engineer therapeutic antibodies with improved functionalities.

  11. Spatial variability of carbon dioxide in the urban canopy layer and implications for flux measurements

    Science.gov (United States)

    Crawford, B.; Christen, A.

    2014-12-01

    This contribution reports CO2 mixing ratios measured in the urban canopy layer (UCL) of a residential neighborhood in Vancouver, BC, Canada and discusses the relevance of UCL CO2 temporal and spatial variability to local-scale eddy covariance (EC) fluxes measured above the UCL. Measurements were conducted from a mobile vehicle-mounted platform over a continuous, 26-h period in the longterm turbulent flux source area of an urban EC tower. Daytime mixing ratios were highest along arterial roads and largely a function of proximity to vehicle traffic CO2 sources. At night, there was a distinct negative correlation between potential air temperature and CO2 mixing ratios. The spatial distribution of CO2 was controlled by topography and micro-scale advective processes (i.e. cold-air pooling). Mobile CO2 measurements were then used to calculate CO2 storage changes (FS) in the UCL volume and compared to single-layer FS estimates calculated from the EC system. In total, five variations of FS were calculated. On average, the choice of FS calculation method affected net measured hourly emissions (FC) by 5.2%. Analysis of FS using a four-year dataset measured at the EC tower show FS was 2.8% of hourly FC for this site on average. At this urban EC location, FS was relatively minor compared to FC and calculation of FS using a single-layer method was adequate, though FS still represents a potentially large uncertainty during individual hours.

  12. Coronal Flux Rope Catastrophe Associated With Internal Energy Release

    Science.gov (United States)

    Zhuang, Bin; Hu, Youqiu; Wang, Yuming; Zhang, Quanhao; Liu, Rui; Gou, Tingyu; Shen, Chenglong

    2018-04-01

    Magnetic energy during the catastrophe was predominantly studied by the previous catastrophe works since it is believed to be the main energy supplier for the solar eruptions. However, the contribution of other types of energies during the catastrophe cannot be neglected. This paper studies the catastrophe of the coronal flux rope system in the solar wind background, with emphasis on the transformation of different types of energies during the catastrophe. The coronal flux rope is characterized by its axial and poloidal magnetic fluxes and total mass. It is shown that a catastrophe can be triggered by not only an increase but also a decrease of the axial magnetic flux. Moreover, the internal energy of the rope is found to be released during the catastrophe so as to provide energy for the upward eruption of the flux rope. As far as the magnetic energy is concerned, it provides only part of the energy release, or even increases during the catastrophe, so the internal energy may act as the dominant or even the unique energy supplier during the catastrophe.

  13. Self Induced Buoyant Blow Off in Upward Flame Spread on Thin Solid Fuels

    Science.gov (United States)

    Johnston, Michael C.; T'ien, James S.; Muff, Derek E.; Olson, Sandra L.; Ferkul, Paul V.

    2013-01-01

    Upward flame spread experiments were conducted on a thin fabric cloth consisting of 75% cotton and 25% fiberglass. The sample is sandwiched symmetrically with stainless steel plates with the exposed width varying between 2 to 8.8 cm from test to test and >1.5m tall. The bottom edge was ignited resulting in a symmetric two sided flame. For the narrower samples (. 5cm), two sided flame growth would proceed until reaching some limiting value (15-30 cm depending on sample width). Fluctuation or instability of the flame base on one side would initially become visible and then the flame base would retreat downstream and cause extinguishment on one side. Detailed examination of the still images shows that the fuel continues to vaporize from the extinguished side due to the thermally thin nature of the fuel. But, due to the remaining inert fiberglass mesh, which acts as a flashback arrestor, the extinguished side was not able to be reignited by the remaining flame. The remaining flame would then shrink in length due to the reduced heat transfer to the solid to a shorter length. The one-sided flame will spread stably with a constant speed and a constant flame length to the end of the sample. A constant length flame implies that the pyrolysis front and the burnt out fronts move at the same speed. For the wider samples (. 7cm), no one-sided extinction is observed. Two-sided flames spread all the way to the top of the sample. For these wider widths, the flames are still growing and have not reached their limiting length if it exists. Care was taken to minimize the amount of non-symmetries in the experimental configuration. Repeated tests show that blow-off can occur on either side of the sample. The flame growth is observed to be very symmetric during the growth phase and grew to significant length (>10cm) before extinction of the flame on one side. Our proposed explanation of this unusual phenomenon (i.e. stronger two ]sided flame cannot exist but weaker one-sided flame can

  14. Antibody-mediated immunity to the obligate intracellular bacterial pathogen Coxiella burnetii is Fc receptor- and complement-independent

    Directory of Open Access Journals (Sweden)

    Heinzen Robert A

    2009-05-01

    Full Text Available Abstract Background The obligate intracellular bacterial pathogen Coxiella burnetii causes the zoonosis Q fever. The intracellular niche of C. burnetii has led to the assumption that cell-mediated immunity is the most important immune component for protection against this pathogen. However, passive immunization with immune serum can protect naïve animals from challenge with virulent C. burnetii, indicating a role for antibody (Ab in protection. The mechanism of this Ab-mediated protection is unknown. Therefore, we conducted a study to determine whether Fc receptors (FcR or complement contribute to Ab-mediated immunity (AMI to C. burnetii. Results Virulent C. burnetii infects and replicates within human dendritic cells (DC without inducing their maturation or activation. We investigated the effects of Ab opsonized C. burnetii on human monocyte-derived and murine bone marrow-derived DC. Infection of DC with Ab-opsonized C. burnetii resulted in increased expression of maturation markers and inflammatory cytokine production. Bacteria that had been incubated with naïve serum had minimal effect on DC, similar to virulent C. burnetii alone. The effect of Ab opsonized C. burnetii on DC was FcR dependent as evidenced by a reduced response of DC from FcR knockout (FcR k/o compared to C57Bl/6 (B6 mice. To address the potential role of FcR in Ab-mediated protection in vivo, we compared the response of passively immunized FcR k/o mice to the B6 controls. Interestingly, we found that FcR are not essential for AMI to C. burnetii in vivo. We subsequently examined the role of complement in AMI by passively immunizing and challenging several different strains of complement-deficient mice and found that AMI to C. burnetii is also complement-independent. Conclusion Despite our data showing FcR-dependent stimulation of DC in vitro, Ab-mediated immunity to C. burnetii in vivo is FcR-independent. We also found that passive immunity to this pathogen is independent of

  15. On the Specification of Upward-Propagating Tides for ICON Science Investigations

    Science.gov (United States)

    Forbes, Jeffrey M.; Zhang, Xiaoli; Hagan, Maura E.; England, Scott L.; Liu, Guiping; Gasperini, Federico

    2017-10-01

    The National Center for Atmospheric Research (NCAR) Thermosphere Ionosphere Electrodynamics General Circulation Model (TIEGCM) will provide a physics-based context for the interpretation of ICON measurements. To optimize the realism of the model simulations, ICON wind and temperature measurements near the ˜97 km lower boundary of the TIEGCM will be used to specify the upward-propagating tidal spectrum at this altitude. This will be done by fitting a set of basis functions called Hough Mode Extensions (HMEs) to 27-day mean tidal winds and temperatures between 90 and 105 km altitude and between 12 °S and 42 °N latitude on a day-by-day basis. The current paper assesses the veracity of the HME fitting methodology given the restricted latitude sampling and the UT-longitude sampling afforded by the MIGHTI instrument viewing from the ICON satellite, which will be in a circular 27° inclination orbit. These issues are investigated using the output from a reanalysis-driven global circulation model, which contains realistic variability of the important tidal components, as a mock data set. ICON sampling of the model reveals that the 27-day mean diurnal and semidiurnal tidal components replicate well the 27-day mean tidal components obtained from full synoptic sampling of the model, but the terdiurnal tidal components are not faithfully reproduced. It is also demonstrated that reconstructed tidal components based on HME fitting to the model tides between 12 °S and 42 °N latitude provide good approximations to the major tidal components expected to be encountered during the ICON mission. This is because the constraints provided by fitting both winds and temperatures over the 90-105 km height range are adequate to offset the restricted sampling in latitude. The boundary conditions provided by the methodology described herein will greatly enhance the ability of the TIEGCM to provide a physical framework for interpreting atmosphere-ionosphere coupling in ICON observations

  16. Upward migration of Vesuvius magma chamber over the past 20,000 years.

    Science.gov (United States)

    Scaillet, B; Pichavant, M; Cioni, R

    2008-09-11

    Forecasting future eruptions of Vesuvius is an important challenge for volcanologists, as its reawakening could threaten the lives of 700,000 people living near the volcano. Critical to the evaluation of hazards associated with the next eruption is the estimation of the depth of the magma reservoir, one of the main parameters controlling magma properties and eruptive style. Petrological studies have indicated that during past activity, magma chambers were at depths between 3 and 16 km (refs 3-7). Geophysical surveys have imaged some levels of seismic attenuation, the shallowest of which lies at 8-9 km depth, and these have been tentatively interpreted as levels of preferential magma accumulation. By using experimental phase equilibria, carried out on material from four main explosive events at Vesuvius, we show here that the reservoirs that fed the eruptive activity migrated from 7-8 km to 3-4 km depth between the ad 79 (Pompeii) and ad 472 (Pollena) events. If data from the Pomici di Base event 18.5 kyr ago and the 1944 Vesuvius eruption are included, the total upward migration of the reservoir amounts to 9-11 km. The change of preferential magma ponding levels in the upper crust can be attributed to differences in the volatile content and buoyancy of ascending magmas, as well as to changes in local stress field following either caldera formation or volcano spreading. Reservoir migration, and the possible influence on feeding rates, should be integrated into the parameters used for defining expected eruptive scenarios at Vesuvius.

  17. Pattern recognition techniques for horizontal and vertically upward multiphase flow measurement

    Science.gov (United States)

    Arubi, Tesi I. M.; Yeung, Hoi

    2012-03-01

    The oil and gas industry need for high performing and low cost multiphase meters is ever more justified given the rapid depletion of conventional oil reserves that has led oil companies to develop smaller and marginal fields and reservoirs in remote locations and deep offshore, thereby placing great demands for compact and more cost effective solutions of on-line continuous multiphase flow measurement for well testing, production monitoring, production optimisation, process control and automation. The pattern recognition approach for clamp-on multiphase measurement employed in this study provides one means for meeting this need. High speed caesium-137 radioisotope-based densitometers were installed vertically at the top of a 50.8mm and 101.6mm riser as well as horizontally at the riser base in the Cranfield University multiphase flow test facility. A comprehensive experimental campaign comprising flow conditions typical of operating conditions found in the Petroleum Industry was conducted. The application of a single gamma densitometer unit, in conjunction with pattern recognition techniques to determine both the phase volume fractions and velocities to yield the individual phase flow rates of horizontal and vertically upward multiphase flows was investigated. The pattern recognition systems were trained to map the temporal fluctuations in the multiphase mixture density with the individual phase flow rates using statistical features extracted from the gamma counts signals as their inputs. Initial results yielded individual phase flow rate predictions to within ±5% relative error for the two phase airwater flows and ±10% for three phase air-oil-water flows data.

  18. Upward Altitudinal Shifts in Habitat Suitability of Mountain Vipers since the Last Glacial Maximum.

    Directory of Open Access Journals (Sweden)

    Masoud Yousefi

    Full Text Available We determined the effects of past and future climate changes on the distribution of the Montivipera raddei species complex (MRC that contains rare and endangered viper species limited to Iran, Turkey and Armenia. We also investigated the current distribution of MRC to locate unidentified isolated populations as well as to evaluate the effectiveness of the current network of protected areas for their conservation. Present distribution of MRC was modeled based on ecological variables and model performance was evaluated by field visits. Some individuals at the newly identified populations showed uncommon morphological characteristics. The distribution map of MRC derived through modeling was then compared with the distribution of protected areas in the region. We estimated the effectiveness of the current protected area network to be 10%, which would be sufficient for conserving this group of species, provided adequate management policies and practices are employed. We further modeled the distribution of MRC in the past (21,000 years ago and under two scenarios in the future (to 2070. These models indicated that climatic changes probably have been responsible for an upward shift in suitable habitats of MRC since the Last Glacial Maximum, leading to isolation of allopatric populations. Distribution will probably become much more restricted in the future as a result of the current rate of global warming. We conclude that climate change most likely played a major role in determining the distribution pattern of MRC, restricting allopatric populations to mountaintops due to habitat alterations. This long-term isolation has facilitated unique local adaptations among MRC populations, which requires further investigation. The suitable habitat patches identified through modeling constitute optimized solutions for inclusion in the network of protected areas in the region.

  19. ASME AG-1 Section FC Qualified HEPA Filters; a Particle Loading Comparison - 13435

    International Nuclear Information System (INIS)

    Stillo, Andrew; Ricketts, Craig I.

    2013-01-01

    High Efficiency Particulate Air (HEPA) Filters used to protect personnel, the public and the environment from airborne radioactive materials are designed, manufactured and qualified in accordance with ASME AG-1 Code section FC (HEPA Filters) [1]. The qualification process requires that filters manufactured in accordance with this ASME AG-1 code section must meet several performance requirements. These requirements include performance specifications for resistance to airflow, aerosol penetration, resistance to rough handling, resistance to pressure (includes high humidity and water droplet exposure), resistance to heated air, spot flame resistance and a visual/dimensional inspection. None of these requirements evaluate the particle loading capacity of a HEPA filter design. Concerns, over the particle loading capacity, of the different designs included within the ASME AG-1 section FC code[1], have been voiced in the recent past. Additionally, the ability of a filter to maintain its integrity, if subjected to severe operating conditions such as elevated relative humidity, fog conditions or elevated temperature, after loading in use over long service intervals is also a major concern. Although currently qualified HEPA filter media are likely to have similar loading characteristics when evaluated independently, filter pleat geometry can have a significant impact on the in-situ particle loading capacity of filter packs. Aerosol particle characteristics, such as size and composition, may also have a significant impact on filter loading capacity. Test results comparing filter loading capacities for three different aerosol particles and three different filter pack configurations are reviewed. The information presented represents an empirical performance comparison among the filter designs tested. The results may serve as a basis for further discussion toward the possible development of a particle loading test to be included in the qualification requirements of ASME AG-1

  20. ASME AG-1 Section FC Qualified HEPA Filters; a Particle Loading Comparison - 13435

    Energy Technology Data Exchange (ETDEWEB)

    Stillo, Andrew [Camfil Farr, 1 North Corporate Drive, Riverdale, NJ 07457 (United States); Ricketts, Craig I. [New Mexico State University, Department of Engineering Technology and Surveying Engineering, P.O. Box 30001 MSC 3566, Las Cruces, NM 88003-8001 (United States)

    2013-07-01

    High Efficiency Particulate Air (HEPA) Filters used to protect personnel, the public and the environment from airborne radioactive materials are designed, manufactured and qualified in accordance with ASME AG-1 Code section FC (HEPA Filters) [1]. The qualification process requires that filters manufactured in accordance with this ASME AG-1 code section must meet several performance requirements. These requirements include performance specifications for resistance to airflow, aerosol penetration, resistance to rough handling, resistance to pressure (includes high humidity and water droplet exposure), resistance to heated air, spot flame resistance and a visual/dimensional inspection. None of these requirements evaluate the particle loading capacity of a HEPA filter design. Concerns, over the particle loading capacity, of the different designs included within the ASME AG-1 section FC code[1], have been voiced in the recent past. Additionally, the ability of a filter to maintain its integrity, if subjected to severe operating conditions such as elevated relative humidity, fog conditions or elevated temperature, after loading in use over long service intervals is also a major concern. Although currently qualified HEPA filter media are likely to have similar loading characteristics when evaluated independently, filter pleat geometry can have a significant impact on the in-situ particle loading capacity of filter packs. Aerosol particle characteristics, such as size and composition, may also have a significant impact on filter loading capacity. Test results comparing filter loading capacities for three different aerosol particles and three different filter pack configurations are reviewed. The information presented represents an empirical performance comparison among the filter designs tested. The results may serve as a basis for further discussion toward the possible development of a particle loading test to be included in the qualification requirements of ASME AG-1

  1. L-fucose in crystal structures of IgG-Fc: Reinterpretation of experimental data

    Czech Academy of Sciences Publication Activity Database

    Kolenko, Petr; Skálová, Tereza; Dohnálek, Jan; Hašek, Jindřich

    2008-01-01

    Roč. 73, č. 5 (2008), s. 608-615 ISSN 0010-0765 R&D Projects: GA ČR GA305/07/1073 Grant - others:FP6-2005-LifeSciHealth-6(EU) LSHG-CT-2006-031220 Institutional research plan: CEZ:AV0Z40500505 Source of funding: R - rámcový projekt EK Keywords : immunoglobulin * Fc-fragment * fucose Subject RIV: CD - Macromolecular Chemistry Impact factor: 0.784, year: 2008

  2. Gamma interferon augments Fc gamma receptor-mediated dengue virus infection of human monocytic cells.

    OpenAIRE

    Kontny, U; Kurane, I; Ennis, F A

    1988-01-01

    It has been reported that anti-dengue antibodies at subneutralizing concentrations augment dengue virus infection of monocytic cells. This is due to the increased uptake of dengue virus in the form of virus-antibody complexes by cells via Fc gamma receptors. We analyzed the effects of recombinant human gamma interferon (rIFN-gamma) on dengue virus infection of human monocytic cells. U937 cells, a human monocytic cell line, were infected with dengue virus in the form of virus-antibody complexe...

  3. Activatory and inhibitory Fcγ receptors augment rituximab-mediated internalization of CD20 independent of signaling via the cytoplasmic domain.

    Science.gov (United States)

    Vaughan, Andrew T; Chan, Claude H T; Klein, Christian; Glennie, Martin J; Beers, Stephen A; Cragg, Mark S

    2015-02-27

    Type I anti-CD20 mAb such as rituximab and ofatumumab engage with the inhibitory FcγR, FcγRIIb on the surface of B cells, resulting in immunoreceptor tyrosine-based inhibitory motif (ITIM) phosphorylation. Internalization of the CD20·mAb·FcγRIIb complex follows, the rate of which correlates with FcγRIIb expression. In contrast, although type II anti-CD20 mAb such as tositumomab and obinutuzumab also interact with and activate FcγRIIb, this interaction fails to augment the rate of CD20·mAb internalization, raising the question of whether ITIM phosphorylation plays any role in this process. We have assessed the molecular requirements for the internalization process and demonstrate that in contrast to internalization of IgG immune complexes, FcγRIIb-augmented internalization of rituximab-ligated CD20 occurs independently of the FcγRIIb ITIM, indicating that signaling downstream of FcγRIIb is not required. In transfected cells, activatory FcγRI, FcγRIIa, and FcγRIIIa augmented internalization of rituximab-ligated CD20 in a similar manner. However, FcγRIIa mediated a slower rate of internalization than cells expressing equivalent levels of the highly homologous FcγRIIb. The difference was maintained in cells expressing FcγRIIa and FcγRIIb lacking cytoplasmic domains and in which the transmembrane domains had been exchanged. This difference may be due to increased degradation of FcγRIIa, which traffics to lysosomes independently of rituximab. We conclude that the cytoplasmic domain of FcγR is not required for promoting internalization of rituximab-ligated CD20. Instead, we propose that FcγR provides a structural role in augmenting endocytosis that differs from that employed during the endocytosis of immune complexes. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  4. NEW ROLES FOR FC RECEPTORS IN NEURODEGENERATION-THE IMPACT ON IMMUNOTHERAPY FOR ALZHEIMER’S DISEASE

    Directory of Open Access Journals (Sweden)

    James P. Fuller

    2014-08-01

    Full Text Available There are an estimated 18 million Alzheimer’s disease (AD sufferers worldwide and with no disease modifying treatment currently available, development of new therapies represents an enormous unmet clinical need. AD is characterised by episodic memory loss followed by severe cognitive decline and is associated with many neuropathological changes. AD is characterised by deposits of amyloid beta (Aβ, neurofibrillary tangles, and neuroinflammation. Active immunisation or passive immunisation against Aβ leads to the clearance of deposits in transgenic mice expressing human Aβ. This clearance is associated with reversal of associated cognitive deficits, but these results have failed to translate to humans, with both active and passive immunotherapy failing to improve memory loss. One explanation for these observations is that certain anti-Aβ antibodies mediate damage to the cerebral vasculature limiting the top dose and potentially reducing efficacy. Fc gamma receptors (Fcγ are a family of immunoglobulin like receptors which bind to the Fc portion of IgG, and mediate the response of effector cells to immune complexes. Data from both mouse and human studies suggest that cross-linking Fc receptors by therapeutic antibodies and the subsequent pro-inflammatory response mediates the vascular side effects seen following immunotherapy. Increasing evidence is emerging that Fc receptor expression on CNS resident cells, including microglia and neurons, is increased during aging and functionally involved in the pathogenesis of age-related neurodegenerative diseases. We propose that increased expression and ligation of Fc receptors in the CNS, either by endogenous IgG or therapeutic antibodies, has the potential to induce vascular damage and exacerbate neurodegeneration. To produce safe and effective immunotherapies for AD and other neurodegenerative diseases it will be vital to understand the role of Fc receptors in the healthy and diseased brain.

  5. Fyn kinase controls Fc{epsilon}RI receptor-operated calcium entry necessary for full degranulation in mast cells

    Energy Technology Data Exchange (ETDEWEB)

    Sanchez-Miranda, Elizabeth; Ibarra-Sanchez, Alfredo [Departamento de Farmacobiologia, Centro de Investigacion y de Estudios Avanzados (Cinvestav), Sede Sur, Calzada de los Tenorios 235, Col. Granjas Coapa, CP 14330 Mexico City (Mexico); Gonzalez-Espinosa, Claudia, E-mail: cgonzal@cinvestav.mx [Departamento de Farmacobiologia, Centro de Investigacion y de Estudios Avanzados (Cinvestav), Sede Sur, Calzada de los Tenorios 235, Col. Granjas Coapa, CP 14330 Mexico City (Mexico)

    2010-01-22

    IgE-antigen-dependent crosslinking of the high affinity IgE receptor (Fc{epsilon}RI) on mast cells leads to degranulation, leukotriene synthesis and cytokine production. Calcium (Ca{sup 2+}) mobilization is a sine qua non requisite for degranulation, allowing the rapid secretion of stored pro-inflammatory mediators responsible for allergy symptoms. Fyn is a Src-family kinase that positively controls Fc{epsilon}RI-induced mast cell degranulation. However, our understanding of the mechanism connecting Fyn activation to secretion of pre-synthesized mediators is very limited. We analyzed Fc{epsilon}RI-dependent Ca{sup 2+} mobilization in bone marrow-derived mast cells (BMMCs) differentiated from WT and Fyn -/- knock out mice. Fyn -/- BMMCs showed a marked defect in extracellular Ca{sup 2+} influx after Fc{epsilon}RI crosslinking but not after thapsigargin addition. High concentrations of Gadolinium (Gd{sup 3+}) partially blocked Fc{epsilon}RI-induced Ca{sup 2+} influx in WT cells but, in contrast, completely inhibited Ca{sup 2+} mobilization in Fyn -/- cells. Low concentrations of an inhibitor of the canonical transient receptor potential (TRPC) Ca{sup 2+} channels (2-aminoethoxyphenyl-borane, 2-APB) blocked Fc{epsilon}RI-induced maximal Ca{sup 2+} rise in WT but not in Fyn -/- cells. Ca{sup 2+} entry through Fyn-controlled, 2-APB sensitive channels was found to be important for full degranulation and IL-2 mRNA accumulation in WT cells. Immunoprecipitation assays showed that Fyn kinase interacts with TRPC 3/6/7 channels after IgE-antigen stimulation, but its association is not related to protein tyrosine phosphorylation. Results indicate Fyn kinase mediates the receptor-dependent activation of TRPC channels that contribute to degranulation in Fc{epsilon}RI-stimulated mast cells.

  6. Continuous magnetic flux pump

    Science.gov (United States)

    Hildebrandt, A. F.; Elleman, D. D.; Whitmore, F. C. (Inventor)

    1966-01-01

    A method and means for altering the intensity of a magnetic field by transposing flux from one location to the location desired fro the magnetic field are examined. The device described includes a pair of communicating cavities formed in a block of superconducting material, is dimensioned to be insertable into one of the cavities and to substantially fill the cavity. Magnetic flux is first trapped in the cavities by establishing a magnetic field while the superconducting material is above the critical temperature at which it goes superconducting. Thereafter, the temperature of the material is reduced below the critical value, and then the exciting magnetic field may be removed. By varying the ratios of the areas of the two cavities, it is possible to produce a field having much greater flux density in the second, smaller cavity, into which the flux transposed.

  7. Flux in Tallinn

    Index Scriptorium Estoniae

    2004-01-01

    Rahvusvahelise elektroonilise kunsti sümpoosioni ISEA2004 klubiõhtu "Flux in Tallinn" klubis Bon Bon. Eestit esindasid Ropotator, Ars Intel Inc., Urmas Puhkan, Joel Tammik, Taavi Tulev (pseud. Wochtzchee). Klubiõhtu koordinaator Andres Lõo

  8. Flux shunts for undulators

    International Nuclear Information System (INIS)

    Hoyer, E.; Chin, J.; Hassenzahl, W.V.

    1993-05-01

    Undulators for high-performance applications in synchrotron-radiation sources and periodic magnetic structures for free-electron lasers have stringent requirements on the curvature of the electron's average trajectory. Undulators using the permanent magnet hybrid configuration often have fields in their central region that produce a curved trajectory caused by local, ambient magnetic fields such as those of the earth. The 4.6 m long Advanced Light Source (ALS) undulators use flux shunts to reduce this effect. These flux shunts are magnetic linkages of very high permeability material connecting the two steel beams that support the magnetic structures. The shunts reduce the scalar potential difference between the supporting beams and carry substantial flux that would normally appear in the undulator gap. Magnetic design, mechanical configuration of the flux shunts and magnetic measurements of their effect on the ALS undulators are described

  9. Flux creep and penetration in Fe-doped YBa2Cu3O7

    International Nuclear Information System (INIS)

    Mohamed, M.A.; Jung, J.; Franck, J.P.

    1990-01-01

    Measurements of the magnetic-field distribution, flux penetration, and decay of trapped flux were performed for a disc-shaped sample of YBa 2 Cu 2.95 Fe 0.05 O 7-δ at 77 K. Time-dependent magnetic-flux penetration, i.e., a decay of diamagnetic shielding and the Meissner field, was observed for zero-field-cooled (ZFC) and field-cooled (FC) samples. The decays were found to be logarithmic in time. The logarithmic decay rate of diamagnetic shielding depends on an applied magnetic field and reaches its maximum at an applied field of about 30 G. The dependence of a trapped field versus an applied field shows a maximum at an applied field of 100 G for the FC case and 200 G for the ZFC case. The maximum amount of the trapped field is about two times less than that for a pure, undoped YBa 2 Cu 3 O 7-δ sample of similar dimensions. The logarithmic decay rate of the trapped field versus the initial trapped field is described by a linear function with the change of its slope at the trapped field corresponding to an applied field of about 30 G for both the FC and ZFC cases. These results are related to the sample microstructure, i.e., grain size and porosity. Trapped field decays can be explained in terms of the interaction between intergranular vortices and persistent current circulating around normal regions or voids, in the framework of the conventional flux-creep model recently proposed by Hagen, Griessen, and Salomons [Physica 157C, 199 (1989)

  10. Neutron flux monitor

    International Nuclear Information System (INIS)

    Oda, Naotaka.

    1993-01-01

    The device of the present invention greatly saves an analog processing section such as an analog filter and an analog processing circuit. That is, the device of the present invention comprises (1) a neutron flux detection means for detecting neutron fluxed in the reactor, (2) a digital filter means for dividing signals corresponding to the detected neutron fluxes into predetermined frequency band regions, (3) a calculation processing means for applying a calculation processing corresponding to the frequency band regions to the neutron flux detection signals divided by the digital filter means. With such a constitution, since the neutron detection signals are processed by the digital filter means, the accuracy is improved and the change for the property of the filter is facilitated. Further, when a neutron flux level is obtained, a calculation processing corresponding to the frequency band region can be conducted without the analog processing circuit. Accordingly, maintenance and accuracy are improved by greatly decreasing the number of parts. Further, since problems inherent to the analog circuit are solved, neutron fluxes are monitored at high reliability. (I.S.)

  11. Neutron flux monitoring device

    International Nuclear Information System (INIS)

    Shimazu, Yoichiro.

    1995-01-01

    In a neutron flux monitoring device, there are disposed a neutron flux measuring means for outputting signals in accordance with the intensity of neutron fluxes, a calculation means for calculating a self power density spectrum at a frequency band suitable to an object to be measured based on the output of the neutron flux measuring means, an alarm set value generation means for outputting an alarm set value as a comparative reference, and an alarm judging means for comparing the alarm set value with the outputted value of the calculation means to judge requirement of generating an alarm and generate an alarm in accordance with the result of the judgement. Namely, the time-series of neutron flux signals is put to fourier transformation for a predetermined period of time by the calculation means, and from each of square sums for real number component and imaginary number component for each of the frequencies, a self power density spectrum in the frequency band suitable to the object to be measured is calculated. Then, when the set reference value is exceeded, an alarm is generated. This can reliably prevent generation of erroneous alarm due to neutron flux noises and can accurately generate an alarm at an appropriate time. (N.H.)

  12. Heat Transfer Characteristics for an Upward Flowing Supercritical Pressure CO2 in a Vertical Annulus Passage

    International Nuclear Information System (INIS)

    Kang, Deog Ji; Kim, Sin; Kim, Hwan Yeol; Bae, Yoon Yeong

    2007-01-01

    Heat transfer experiments at a vertical annulus passage were carried out in the SPHINX(Supercritical Pressure Heat Transfer Investigation for NeXt Generation) to investigate the heat transfer behaviors of supercritical CO 2 . The collected test data are to be used for the reactor core design of the SCWR (SuperCritical Water-cooled Reactor). The mass flux was in the range of 400 ∼1200 kg/m 2 s and the heat flux was chosen up to 150 kW/m 2 . The selected pressures were 7.75 and 8.12 MPa. The heat transfer data were analyzed and compared with the previous tube test data. The test results showed that the heat transfer characteristics were similar to those of the tube in case of a normal heat transfer mode and degree of heat transfer deterioration became smaller than that in the tube. Comparison of the experimental heat transfer coefficients with the predicted ones by the existing correlations showed that there was not a distinct difference between the correlations

  13. Heat-Transfer characteristics of Supercritical Water flowing upward in bare-tubes

    Energy Technology Data Exchange (ETDEWEB)

    Sidawi, K., E-mail: khalil.sidawi@uoit.ca [University of Ontario Institute of Technology, Faculty of Energy Systems and Nuclear Sciences, Oshawa, ON (Canada)

    2015-07-01

    There has been many correlations developed for Supercritical Water (SCW) flowing in bare-tubes. These correlations, generally, have limits based on the experimental trials. However, this does not indicate the true range to which these correlations can be applied. Furthermore, increases in heat flux and decreases in mass flux have been known to lead to Deteriorated Heat-Transfer (DHT). One way to classify fluids in the supercritical region is to use the Eckert Number to differentiate between two different sub-states{sup 1} ; when T < T{sub pc}, SCW is considered to be liquid-like, whereas at T > T{sub pc}, SCW is considered to be gas-like. There is a significant decrease in RMS error for calculated HTC in trials where there is a single sub-state across the cross-section. Trials where there is a combination of sub-states have drastically higher RMS error for HTC. Furthermore, some trials indicate a decrease in HTC at the interphase between the two sub-states. (author)

  14. Cholecystokinin (CCK) functional cholescintigraphy (FC) in patients suspected of acalculous biliary disease (ABD)

    International Nuclear Information System (INIS)

    Fink-Bennett, D.; De Ridder, P.; Kolozsi, W.; Gordon, R.; Rapp, J.

    1984-01-01

    To determine if CCK FC can aid in the diagnosis (Dx.) of ABD, the authors retrospectively analyzed the max. gallbladder (GB) ejection fraction response (EFR) to CCK in 240 patients (pts.) with persistent symptoms of biliary colic, a normal GB Ultrasound exam and/or OCG. Each pt. (NPO after 12 A.M.) received 5 mCi of technetium (Tc)-99 Hepatolite. After max GB filling, .02 μg/kg CCK was administered (1-3 minutes) I.V. Background corrected GB EFs were determined q.5 min x4 by ratioing the pre-CCK GB cts. minus post-CCK GB cts. to pre-CCK GB cts. In 131/240 pts. the max. GBEFR was 35%. Eleven underwent surgery, 98 medical Rx. 4/11 Cx. apts had CAC, 7 were normal. Of the 98 medical Rx. pts. 21 lack followup, 71 are clinically felt not to have ABD; 6 are felt to have ABD. CCK FC appears to be a useful test for the detection of ABD. Its predictive value (GBEF <35%) in Cx. pts. is 97%; in all pts. (assuming medical Rx. correct), 94% (sensitivity - 91%, specificity - 93%)

  15. A potent human neutralizing antibody Fc-dependently reduces established HBV infections.

    Science.gov (United States)

    Li, Dan; He, Wenhui; Liu, Ximing; Zheng, Sanduo; Qi, Yonghe; Li, Huiyu; Mao, Fengfeng; Liu, Juan; Sun, Yinyan; Pan, Lijing; Du, Kaixin; Ye, Keqiong; Li, Wenhui; Sui, Jianhua

    2017-09-26

    Hepatitis B virus (HBV) infection is a major global health problem. Currently-available therapies are ineffective in curing chronic HBV infection. HBV and its satellite hepatitis D virus (HDV) infect hepatocytes via binding of the preS1 domain of its large envelope protein to sodium taurocholate cotransporting polypeptide (NTCP). Here, we developed novel human monoclonal antibodies that block the engagement of preS1 with NTCP and neutralize HBV and HDV with high potency. One antibody, 2H5-A14, functions at picomolar level and exhibited neutralization-activity-mediated prophylactic effects. It also acts therapeutically by eliciting antibody-Fc-dependent immunological effector functions that impose durable suppression of viral infection in HBV-infected mice, resulting in reductions in the levels of the small envelope antigen and viral DNA, with no emergence of escape mutants. Our results illustrate a novel antibody-Fc-dependent approach for HBV treatment and suggest 2H5-A14 as a novel clinical candidate for HBV prevention and treatment of chronic HBV infection.

  16. Rab20 regulates phagosome maturation in RAW264 macrophages during Fc gamma receptor-mediated phagocytosis.

    Directory of Open Access Journals (Sweden)

    Youhei Egami

    Full Text Available Rab20, a member of the Rab GTPase family, is known to be involved in membrane trafficking, however its implication in FcγR-mediated phagocytosis is unclear. We examined the spatiotemporal localization of Rab20 during phagocytosis of IgG-opsonized erythrocytes (IgG-Es in RAW264 macrophages. By the live-cell imaging of fluorescent protein-fused Rab20, it was shown that Rab20 was transiently associated with the phagosomal membranes. During the early stage of phagosome formation, Rab20 was not localized on the membranes of phagocytic cups, but was gradually recruited to the newly formed phagosomes. Although Rab20 was colocalized with Rab5 to some extent, the association of Rab20 with the phagosomes persisted even after the loss of Rab5 from the phagosomal membranes. Then, Rab20 was colocalized with Rab7 and Lamp1, late endosomal/lysosomal markers, on the internalized phagosomes. Moreover, our analysis of Rab20 mutant expression revealed that the maturation of phagosomes was significantly delayed in cells expressing the GDP-bound mutant Rab20-T19N. These data suggest that Rab20 is an important component of phagosome and regulates the phagosome maturation during FcγR-mediated phagocytosis.

  17. Investigating spatial variability of vertical water fluxes through the streambed in distinctive stream morphologies using temperature and head data

    Science.gov (United States)

    Wang, Liping; Jiang, Weiwei; Song, Jinxi; Dou, Xinyi; Guo, Hongtao; Xu, Shaofeng; Zhang, Guotao; Wen, Ming; Long, Yongqing; Li, Qi

    2017-08-01

    Investigating the interaction of groundwater and surface water is key to understanding the hyporheic processes. The vertical water fluxes through a streambed were determined using Darcian flux calculations and vertical sediment temperature profiles to assess the pattern and magnitude of groundwater/surface-water interaction in Beiluo River, China. Field measurements were taken in January 2015 at three different stream morphologies including a meander bend, an anabranching channel and a straight stream channel. Despite the differences of flux direction and magnitude, flux directions based on vertical temperature profiles are in good agreement with results from Darcian flux calculations at the anabranching channel, and the Kruskal-Wallis tests show no significant differences between the estimated upward fluxes based on the two methods at each site. Also, the upward fluxes based on the two methods show similar spatial distributions on the streambed, indicating (1) that higher water fluxes at the meander bend occur from the center of the channel towards the erosional bank, (2) that water fluxes at the anabranching channel are higher near the erosional bank and in the center of the channel, and (3) that in the straight channel, higher water fluxes appear from the center of the channel towards the depositional bank. It is noted that higher fluxes generally occur at certain locations with higher streambed vertical hydraulic conductivity ( K v) or where a higher vertical hydraulic gradient is observed. Moreover, differences of grain size, induced by stream morphology and contrasting erosional and depositional conditions, have significant effects on streambed K v and water fluxes.

  18. Dual role of Fcγ receptors in host defense and disease in Borrelia burgdorferi-infected mice

    Directory of Open Access Journals (Sweden)

    Alexia Anne Belperron

    2014-06-01

    Full Text Available Arthritis in mice infected with the Lyme disease spirochete, Borrelia burgdorferi, results from the influx of innate immune cells responding to the pathogen in the joint and is influenced in part by mouse genetics. Production of inflammatory cytokines by innate immune cells in vitro is largely mediated by Toll-like receptor (TLR interaction with Borrelia lipoproteins, yet surprisingly mice deficient in TLR2 or the TLR signaling molecule MyD88 still develop arthritis comparable to that seen in wild type mice after B. burgdorferi infection. These findings suggest that other, MyD88-independent inflammatory pathways can contribute to arthritis expression. Clearance of B. burgdorferi is dependent on the production of specific antibody and phagocytosis of the organism. As Fc receptors (FcγR are important for IgG-mediated clearance of immune complexes and opsonized particles by phagocytes, we examined the role that FcγR play in host defense and disease in B. burgdorferi-infected mice. B. burgdorferi-infected mice deficient in the Fc receptor common gamma chain (FcεRγ-/- mice harbored ~10 fold more spirochetes than similarly infected wild type mice, and this was associated with a transient increase in arthritis severity. While the elevated pathogen burdens seen in B. burgdorferi-infected MyD88-/- mice were not affected by concomitant deficiency in FcγR, arthritis was reduced in FcεRγ-/-MyD88-/- mice in comparison to wild type or single knockout mice. Gene expression analysis from infected joints demonstrated that absence of both MyD88 and FcγR lowers mRNA levels of proteins involved in inflammation, including Cxcl1 (KC, Xcr1 (Gpr5, IL-1beta, and C reactive protein. Taken together, our results demonstrate a role for FcγR-mediated immunity in limiting pathogen burden and arthritis in mice during the acute phase of B. burgdorferi infection, and further suggest that this pathway contributes to the arthritis that develops in B. burgdorferi

  19. Isotopic versus micrometeorologic ocean CO2 fluxes: A serious conflict

    International Nuclear Information System (INIS)

    Broecker, W.S.; Ledwell, J.R.; Takahashi, T.; Weiss, R.; Merlivat, L.; Memery, L.; Tsung-Hung Peng; Jahne, B.; Otto Munnich, K.

    1986-01-01

    Eddy correlation measurements over the ocean give CO 2 fluxes an order of magnitude or more larger than expected from mass balance or more larger than expected from mass balance measurements using radiocarbon and radon 222. In particular, Smith and Jones (1985) reported large upward and downward fluxes in a surf zone at supersaturations of 15% and attributed them to the equilibration of bubbles at elevated pressures. They argue that even on the open ocean such bubble injection may create steady state CO 2 supersaturations and that inferences of fluxes based on air-sea pCO 2 differences and radon exchange velocities must be made with caution. We defend the global average CO 2 exchange rate determined by three independent radioisotopic means: prebomb radiocarbon inventories; global surveys of mixed layer radon deficits; and oceanic uptake of bomb-produced radiocarbon. We argue that laboratory and lake data do not lead one to expect fluxes as large as reported from the eddy correlation technique; that the radon method of determining exchange velocities is indeed useful for estimating CO 2 fluxes; that supersaturations of CO 2 due to bubble injection on the open ocean are negligible; that the hypothesis that Smith and Jones advance cannot account for the fluxes that they report; and that the pCO 2 values reported by Smith and Jones are likely to be systematically much too high. The CO 2 fluxes for the ocean measured to data by the micrometeorological method can be reconciled with neither the observed concentrations of radioisotopes of radon and carbon in the oceans nor the tracer experiments carried out in lakes and in wind/wave tunnels

  20. Antibody-dependent cellular cytotoxicity and cytokine/chemokine secretion by KHYG-1 cells stably expressing FcγRIIIA.

    Science.gov (United States)

    Kobayashi, Eiji; Motoi, Sotaro; Sugiura, Masahito; Kajikawa, Masunori; Kojima, Shuji; Kohroki, Junya; Masuho, Yasuhiko

    2014-09-01

    Antibody-dependent cellular cytotoxicity (ADCC) mediated by natural killer (NK) cells is a major mechanism of tumor therapy with antibodies. NK cells not only manifest cytotoxicity but also secrete a variety of cytokines/chemokines that regulate immune responses. Using a retroviral vector, in this study we established a KHYG-1 cell line that stably expresses FcγRIIIA (CD16A). The KHYG-1/FcγRIIIA cells exerted potent antibody concentration-dependent ADCC, whereas parental KHYG-1 cells did not. In contrast, without antibody, the natural killer activity of KHYG-1/FcγRIIIA cells was less potent than that of parental KHYG-1 cells. During the course of ADCC, KHYG-1/FcγRIIIA cells secreted IFN-γ and MIP-1α dependent upon antibody concentration, but parental KHYG-1 cells did not. These results suggest that KHYG-1/FcγRIIIA cells would be useful in studies to elucidate the function of NK cells and the mechanism of ADCC. Copyright © 2014 Elsevier B.V. All rights reserved.

  1. Effects of CTLA4-Fc on glomerular injury in humorally-mediated glomerulonephritis in BALB/c mice.

    Science.gov (United States)

    Kitching, A R; Huang, X R; Ruth, A-J; Tipping, P G; Holdsworth, S R

    2002-06-01

    The effect of cytotoxic T-lymphocyte-associated molecule 4-immunoglobulin fusion protein (CTLA4-Fc) on humorally-mediated glomerulonephritis was studied in accelerated anti-glomerular basement membrane (anti-GBM) glomerulonephritis induced in BALB/c mice. This strain of mice develops antibody and complement dependent glomerulonephritis under this protocol. Sensitized BALB/c mice developed high levels of circulating autologous antibody titres, intense glomerular deposition of mouse immunoglobulin and complement, significant proteinuria, renal impairment, significant glomerular necrosis and a minor component of crescent formation 10 days after challenge with a nephritogenic antigen (sheep anti-GBM globulin). Early treatment during the primary immune response, or continuous treatment throughout the disease with CTLA4-Fc, significantly suppressed mouse anti-sheep globulin antibody titres in serum, and immunoglobulin and complement deposition in glomeruli. The degree of glomerular necrosis was improved and proteinuria was reduced, particularly in the earlier stages of disease. Late treatment by CTLA4-Fc starting one day after challenge with sheep anti-mouse GBM did not affect antibody production and did not attenuate glomerulonephritis. The low level of crescent formation found in BALB/c mice developing glomerulonephritis was not prevented by the administration of CTLA4-Fc. These results demonstrate that CTLA4-Fc is of benefit in this model of glomerulonephritis by its capacity to attenuate antibody production, without affecting the minor degree of cell-mediated glomerular injury.

  2. Prediction, analysis and solution of flow inversion phenomenon in a typical MTR reactor with upward core cooling

    International Nuclear Information System (INIS)

    El-Morshedy, Salah El-Din

    2010-01-01

    Research reactors of power greater than 20 MW are usually designed to be cooled with upward coolant flow direction inside the reactor core. This is mainly to prevent flow inversion problems following a pump coast down. However, in some designs and under certain operating conditions, flow inversion phenomenon is predicted. In the present work, the best-estimate Material Testing Reactors Thermal-Hydraulic Analysis program (MTRTHA) is used to simulate a typical MTR reactor behavior with upward cooling under a hypothetical case of loss of off-site power. The flow inversion phenomenon is predicted under certain decay heat and/or pool temperature values below the design values. The reactor simulation under loss of off-site power is performed for two cases namely; two-flap valves open and one flap-valve fails to open. The model results for the flow inversion phenomenon prediction is analyzed and a solution of the problem is suggested. (orig.)

  3. The Open Flux Problem

    Science.gov (United States)

    Linker, J. A.; Caplan, R. M.; Downs, C.; Riley, P.; Mikic, Z.; Lionello, R.; Henney, C. J.; Arge, C. N.; Liu, Y.; Derosa, M. L.; Yeates, A.; Owens, M. J.

    2017-10-01

    The heliospheric magnetic field is of pivotal importance in solar and space physics. The field is rooted in the Sun’s photosphere, where it has been observed for many years. Global maps of the solar magnetic field based on full-disk magnetograms are commonly used as boundary conditions for coronal and solar wind models. Two primary observational constraints on the models are (1) the open field regions in the model should approximately correspond to coronal holes (CHs) observed in emission and (2) the magnitude of the open magnetic flux in the model should match that inferred from in situ spacecraft measurements. In this study, we calculate both magnetohydrodynamic and potential field source surface solutions using 14 different magnetic maps produced from five different types of observatory magnetograms, for the time period surrounding 2010 July. We have found that for all of the model/map combinations, models that have CH areas close to observations underestimate the interplanetary magnetic flux, or, conversely, for models to match the interplanetary flux, the modeled open field regions are larger than CHs observed in EUV emission. In an alternative approach, we estimate the open magnetic flux entirely from solar observations by combining automatically detected CHs for Carrington rotation 2098 with observatory synoptic magnetic maps. This approach also underestimates the interplanetary magnetic flux. Our results imply that either typical observatory maps underestimate the Sun’s magnetic flux, or a significant portion of the open magnetic flux is not rooted in regions that are obviously dark in EUV and X-ray emission.

  4. The Open Flux Problem

    Energy Technology Data Exchange (ETDEWEB)

    Linker, J. A.; Caplan, R. M.; Downs, C.; Riley, P.; Mikic, Z.; Lionello, R. [Predictive Science Inc., 9990 Mesa Rim Road, Suite 170, San Diego, CA 92121 (United States); Henney, C. J. [Air Force Research Lab/Space Vehicles Directorate, 3550 Aberdeen Avenue SE, Kirtland AFB, NM (United States); Arge, C. N. [Science and Exploration Directorate, NASA/GSFC, Greenbelt, MD 20771 (United States); Liu, Y. [W. W. Hansen Experimental Physics Laboratory, Stanford University, Stanford, CA 94305 (United States); Derosa, M. L. [Lockheed Martin Solar and Astrophysics Laboratory, 3251 Hanover Street B/252, Palo Alto, CA 94304 (United States); Yeates, A. [Department of Mathematical Sciences, Durham University, Durham, DH1 3LE (United Kingdom); Owens, M. J., E-mail: linkerj@predsci.com [Space and Atmospheric Electricity Group, Department of Meteorology, University of Reading, Earley Gate, P.O. Box 243, Reading RG6 6BB (United Kingdom)

    2017-10-10

    The heliospheric magnetic field is of pivotal importance in solar and space physics. The field is rooted in the Sun’s photosphere, where it has been observed for many years. Global maps of the solar magnetic field based on full-disk magnetograms are commonly used as boundary conditions for coronal and solar wind models. Two primary observational constraints on the models are (1) the open field regions in the model should approximately correspond to coronal holes (CHs) observed in emission and (2) the magnitude of the open magnetic flux in the model should match that inferred from in situ spacecraft measurements. In this study, we calculate both magnetohydrodynamic and potential field source surface solutions using 14 different magnetic maps produced from five different types of observatory magnetograms, for the time period surrounding 2010 July. We have found that for all of the model/map combinations, models that have CH areas close to observations underestimate the interplanetary magnetic flux, or, conversely, for models to match the interplanetary flux, the modeled open field regions are larger than CHs observed in EUV emission. In an alternative approach, we estimate the open magnetic flux entirely from solar observations by combining automatically detected CHs for Carrington rotation 2098 with observatory synoptic magnetic maps. This approach also underestimates the interplanetary magnetic flux. Our results imply that either typical observatory maps underestimate the Sun’s magnetic flux, or a significant portion of the open magnetic flux is not rooted in regions that are obviously dark in EUV and X-ray emission.

  5. Simultaneous removal of organic contaminants and heavy metals from kaolin using an upward electrokinetic soil remediation process

    International Nuclear Information System (INIS)

    Wang, J.-Y.; Huang, X.-J.; Kao, Jimmy C.M.; Stabnikova, Olena

    2007-01-01

    Kaolins contaminated with heavy metals, Cu and Pb, and organic compounds, p-xylene and phenanthrene, were treated with an upward electrokinetic soil remediation (UESR) process. The effects of current density, cathode chamber flushing fluid, treatment duration, reactor size, and the type of contaminants under the vertical non-uniform electric field of UESR on the simultaneous removal of the heavy metals and organic contaminants were studied. The removal efficiencies of p-xylene and phenanthrene were higher in the experiments with cells of smaller diameter or larger height, and with distilled water flow in the cathode chamber. The removal efficiency of Cu and Pb were higher in the experiments with smaller diameter or shorter height cells and 0.01 M HNO 3 solution as cathode chamber flow. In spite of different conditions for removal of heavy metals and organics, it is possible to use the upward electrokinetic soil remediation process for their simultaneous removal. Thus, in the experiments with duration of 6 days removal efficiencies of phenanthrene, p-xylene, Cu and Pb were 67%, 93%, 62% and 35%, respectively. The experiment demonstrated the feasibility of simultaneous removal of organic contaminants and heavy metals from kaolin using the upward electrokinetic soil remediation process

  6. Phase distribution phenomena in upward cocurrent bubbly flows. A critical review of the experimental and theoretical works

    International Nuclear Information System (INIS)

    Grossetete, C.

    1992-09-01

    The most important and challenging problems in two-phase bubbly flow today are related to the physical understanding and the modeling of multidimensional phenomena such as the distribution of phases in space. We present here a critical review of the available experimental and theoretical studies in gas-liquid adiabatic and non-reactive upward bubbly flows which have been carried out to define and improve the physical models needed to close the three-dimensional two-fluid model equations. It appears that: so far, the axial development of two-phase upward bubbly flows has not been handled thoroughly. Little is known about the way the pressure gradient as well as the gas-liquid mixing conditions affect the distribution of phases, the problems related to the closing of the two-fluid model equations are far from being solved. The physical models proposed seem often to be too much complex considering how little we know about the mechanisms involved, there are still very few multidimensional numerical models whose results have been compared with experimental data on bubbly flows. The boundary conditions introduced in the codes as well as the sensitivity of the results to the parameters of the codes are never precisely stated. To bridge some of those gaps, we propose to perform an experimental and numerical study of the axial development of two-phase air-water upward bubbly flows in vertical pipes

  7. Openness to Experience as a Predictor and Outcome of Upward Job Changes into Managerial and Professional Positions

    Science.gov (United States)

    Nieß, Christiane; Zacher, Hannes

    2015-01-01

    In industrial and organizational psychology, there is a long tradition of studying personality as an antecedent of work outcomes. Recently, however, scholars have suggested that personality characteristics may not only predict, but also change due to certain work experiences, a notion that is depicted in the dynamic developmental model (DDM) of personality and work. Upward job changes are an important part of employees’ careers and career success in particular, and we argue that these career transitions can shape personality over time. In this study, we investigate the Big Five personality characteristics as both predictors and outcomes of upward job changes into managerial and professional positions. We tested our hypotheses by applying event history analyses and propensity score matching to a longitudinal dataset collected over five years from employees in Australia. Results indicated that participants’ openness to experience not only predicted, but that changes in openness to experience also followed from upward job changes into managerial and professional positions. Our findings thus provide support for a dynamic perspective on personality characteristics in the context of work and careers. PMID:26110527

  8. An Engineered Disulfide Bond Reversibly Traps the IgE-Fc3-4 in a Closed, Nonreceptor Binding Conformation

    Energy Technology Data Exchange (ETDEWEB)

    Wurzburg, Beth A.; Kim, Beomkyu; Tarchevskaya, Svetlana S.; Eggel, Alexander; Vogel, Monique; Jardetzky, Theodore S. [Bern; (Stanford-MED)

    2013-08-02

    IgE antibodies interact with the high affinity IgE Fc receptor, FcϵRI, and activate inflammatory pathways associated with the allergic response. The IgE-Fc region, comprising the C-terminal domains of the IgE heavy chain, binds FcϵRI and can adopt different conformations ranging from a closed form incompatible with receptor binding to an open, receptor-bound state. A number of intermediate states are also observed in different IgE-Fc crystal forms. To further explore this apparent IgE-Fc conformational flexibility and to potentially trap a closed, inactive state, we generated a series of disulfide bond mutants. Here we describe the structure and biochemical properties of an IgE-Fc mutant that is trapped in the closed, non-receptor binding state via an engineered disulfide at residue 335 (Cys-335). Reduction of the disulfide at Cys-335 restores the ability of IgE-Fc to bind to its high affinity receptor, FcϵRIα. The structure of the Cys-335 mutant shows that its conformation is within the range of previously observed, closed form IgE-Fc structures and that it retains the hydrophobic pocket found in the hinge region of the closed conformation. Locking the IgE-Fc into the closed state with the Cys-335 mutation does not affect binding of two other IgE-Fc ligands, omalizumab and DARPin E2_79, demonstrating selective blocking of the high affinity receptor binding.

  9. Meromorphic flux compactification

    Energy Technology Data Exchange (ETDEWEB)

    Damian, Cesar [Departamento de Ingeniería Mecánica, Universidad de Guanajuato,Carretera Salamanca-Valle de Santiago Km 3.5+1.8 Comunidad de Palo Blanco,Salamanca (Mexico); Loaiza-Brito, Oscar [Departamento de Física, Universidad de Guanajuato,Loma del Bosque No. 103 Col. Lomas del Campestre C.P 37150 León, Guanajuato (Mexico)

    2017-04-26

    We present exact solutions of four-dimensional Einstein’s equations related to Minkoswki vacuum constructed from Type IIB string theory with non-trivial fluxes. Following https://www.doi.org/10.1007/JHEP02(2015)187; https://www.doi.org/10.1007/JHEP02(2015)188 we study a non-trivial flux compactification on a fibered product by a four-dimensional torus and a two-dimensional sphere punctured by 5- and 7-branes. By considering only 3-form fluxes and the dilaton, as functions on the internal sphere coordinates, we show that these solutions correspond to a family of supersymmetric solutions constructed by the use of G-theory. Meromorphicity on functions constructed in terms of fluxes and warping factors guarantees that flux and 5-brane contributions to the scalar curvature vanish while fulfilling stringent constraints as tadpole cancelation and Bianchi identities. Different Einstein’s solutions are shown to be related by U-dualities. We present three supersymmetric non-trivial Minkowski vacuum solutions and compute the corresponding soft terms. We also construct a non-supersymmetric solution and study its stability.

  10. Meromorphic flux compactification

    International Nuclear Information System (INIS)

    Damian, Cesar; Loaiza-Brito, Oscar

    2017-01-01

    We present exact solutions of four-dimensional Einstein’s equations related to Minkoswki vacuum constructed from Type IIB string theory with non-trivial fluxes. Following https://www.doi.org/10.1007/JHEP02(2015)187; https://www.doi.org/10.1007/JHEP02(2015)188 we study a non-trivial flux compactification on a fibered product by a four-dimensional torus and a two-dimensional sphere punctured by 5- and 7-branes. By considering only 3-form fluxes and the dilaton, as functions on the internal sphere coordinates, we show that these solutions correspond to a family of supersymmetric solutions constructed by the use of G-theory. Meromorphicity on functions constructed in terms of fluxes and warping factors guarantees that flux and 5-brane contributions to the scalar curvature vanish while fulfilling stringent constraints as tadpole cancelation and Bianchi identities. Different Einstein’s solutions are shown to be related by U-dualities. We present three supersymmetric non-trivial Minkowski vacuum solutions and compute the corresponding soft terms. We also construct a non-supersymmetric solution and study its stability.

  11. Flux Pinning in Superconductors

    CERN Document Server

    Matsushita, Teruo

    2007-01-01

    The book covers the flux pinning mechanisms and properties and the electromagnetic phenomena caused by the flux pinning common for metallic, high-Tc and MgB2 superconductors. The condensation energy interaction known for normal precipitates or grain boundaries and the kinetic energy interaction proposed for artificial Nb pins in Nb-Ti, etc., are introduced for the pinning mechanism. Summation theories to derive the critical current density are discussed in detail. Irreversible magnetization and AC loss caused by the flux pinning are also discussed. The loss originally stems from the ohmic dissipation of normal electrons in the normal core driven by the electric field induced by the flux motion. The readers will learn why the resultant loss is of hysteresis type in spite of such mechanism. The influence of the flux pinning on the vortex phase diagram in high Tc superconductors is discussed, and the dependencies of the irreversibility field are also described on other quantities such as anisotropy of supercondu...

  12. Quantitation of Fc receptors and surface immunoglobulin is affected by cell isolation procedures using plasmagel and ficoll-hypaque.

    Science.gov (United States)

    Alexander, E L; Titus, J A; Segal, D M

    1978-01-01

    When mononuclear leukocytes are isolated directly from whole human blood using Ficoll-Hypaque or Plasmagel, cytophilic immunoglobulin is detected on cell surfaces. Upon incubation at 37 degrees C, this cell-associated immunoglobulin is shed slowly into the medium. However, when cells are prewashed in phosphate-buffered saline prior to isolation, they appear to be free of cytophilic immunoglobulin. Compared to prewashed cells, populations retaining cytophilic immunoglobulin on their surfaces demonstrate a decreased binding of soluble immune complexes and radiolabelled trimeric rabbit IgG. The data suggest that Ficoll-Hypaque and Plasmagel cause serum IgG to bind with abnormally high affinity to human mononuclear leukocytes, probably via Fc receptors. This artifact of preparation can lead to erroneous estimates of the numbers of cells bearing Fc receptors or intrinsic membrane immunoglobulin within a given population of cells and to an inaccurate assessment of the average number of Fc receptors per cell.

  13. Antibody Responses with Fc-Mediated Functions after Vaccination of HIV-Infected Subjects with Trivalent Influenza Vaccine

    DEFF Research Database (Denmark)

    Kristensen, Anne B; Lay, William N; Ana-Sosa-Batiz, Fernanda

    2016-01-01

    to immunize this at-risk group. IMPORTANCE: Infection with HIV is associated with increasing disease severity following influenza infections, and annual influenza vaccinations are recommended for this target group. However, HIV-infected individuals respond relatively poorly to vaccination compared to healthy......This study seeks to assess the ability of seasonal trivalent inactivated influenza vaccine (TIV) to induce nonneutralizing antibodies (Abs) with Fc-mediated functions in HIV-uninfected and HIV-infected subjects. Functional influenza-specific Ab responses were studied in 30 HIV-negative and 27 HIV......-positive subjects immunized against seasonal influenza. All 57 subjects received the 2015 TIV. Fc-mediated antihemagglutinin (anti-HA) Ab activity was measured in plasma before and 4 weeks after vaccination using Fc-receptor-binding assays, NK cell activation assays, and phagocytosis assays. At baseline, the HIV...

  14. Chicken IgY Fc linked to Bordetella avium ompA and Taishan Pinus massoniana pollen polysaccharide adjuvant enhances macrophage function and specific immune responses

    Directory of Open Access Journals (Sweden)

    Zhu Ruiliang

    2016-11-01

    Full Text Available Fc-fusion technologies, in which immunoglobulin Fc is genetically fused to an antigenic protein, have been developed to confer antibody-like properties to proteins and peptides. Mammalian IgG Fc fusion exhibits improved antigen-induced immune responses by providing aggregates with high avidity for the IgG Fc receptor and salvaging the antigenic portion from endosomal degradation. However, whether the linked chicken IgY Fc fragment shares similar characteristics to mammalian IgG Fc remains unclear. In this study, we linked the chicken IgY Fc gene to the outer membrane protein A (ompA of Borderella avium through overlapping PCR. The fusion gene was cloned into the pPIC9 plasmid to construct the recombinant Pichia pastoris transformant expressing the ompA–Fc fusion protein. The effects of the linked Fc on macrophage vitality, activity, efficiency of antigen processing, and immune responses induced by the fused ompA were investigated. Furthermore, the effect of Taishan Pinus massoniana pollen polysaccharide (TPPPS, an immunomodulator, on chicken macrophage activation was evaluated. TPPPS was also used as an adjuvant to investigate its immunomodulatory effect on immunoresponses induced by the fused ompA–Fc in chickens. The pinocytosis, phagocytosis, secretion of nitric oxide and TNF-α, and MHC-II molecular expression of the macrophages treated with the fused ompA–Fc were significantly higher than those of the macrophages treated with ompA alone. The addition of TPPPS to the fused ompA–Fc further enhanced macrophage functions. The fused ompA–Fc elicited higher antigen-specific immune responses and protective efficacy compared with ompA alone. Moreover, the fused ompA–Fc conferred higher serum antibody titers, serum IL-2 and IL-4 concentrations, CD4+ and CD8+ T-lymphocyte counts, lymphocyte transformation rate, and protection rate compared with ompA alone. Notably, the prepared TPPPS adjuvant ompA–Fc vaccines induced high immune

  15. At least two Fc Neu5Gc residues of monoclonal antibodies are required for binding to anti-Neu5Gc antibody

    OpenAIRE

    Yu, Chuanfei; Gao, Kai; Zhu, Lei; Wang, Wenbo; Wang, Lan; Zhang, Feng; Liu, Chunyu; Li, Meng; Wormald, Mark R.; Rudd, Pauline M.; Wang, Junzhi

    2016-01-01

    Two non-human glycan epitopes, galactose-Į-1,3-galactose (Į-gal) and Neu5Gc-Į-2-6-galactose (Neu5Gc) have been shown to be antigenic when attached to Fab oligosaccharides of monoclonal antibodies (mAbs) , while Į-gal attached to Fc glycans were not. However, the antigenicity of Neu5Gc on the Fc glycans remains unclear in the context that most mAbs carry only Fc glycans. After studying two clinical mAbs carrying significant amounts of Fc Neu5Gc, we show that their binding activity with anti-Ne...

  16. Genetic association of multiple sclerosis with the marker rs391745 near the endogenous retroviral locus HERV-Fc1: analysis of disease subtypes

    DEFF Research Database (Denmark)

    Hansen, Bettina; Oturai, Annette Bang; Harbo, Hanne F

    2011-01-01

    We have previously described the occurrence of multiple sclerosis (MS) to be associated with human endogenous retroviruses, specifically the X-linked viral locus HERV-Fc1. The aim of this study was to investigate a possible association of the HERV-Fc1 locus with subtypes of MS. MS patients......-Fc1 locus (p = 0.003), while primary progressive disease was not. The ability to see genetic differences between subtypes of MS near this gene speaks for the involvement of the virus HERV-Fc1 locus in modifying the disease course of MS....

  17. Recombinant IgG1 Fc hexamers block cytotoxicity and pathological changes in experimental in vitro and rat models of neuromyelitis optica.

    Science.gov (United States)

    Tradtrantip, Lukmanee; Felix, Christian M; Spirig, Rolf; Morelli, Adriana Baz; Verkman, A S

    2018-05-01

    Intravenous human immunoglobulin G (IVIG) may have therapeutic benefit in neuromyelitis optica spectrum disorders (herein called NMO), in part because of the anti-inflammatory properties of the IgG Fc region. Here, we evaluated recombinant Fc hexamers consisting of the IgM μ-tailpiece fused with the Fc region of human IgG1. In vitro, the Fc hexamers prevented cytotoxicity in aquaporin-4 (AQP4) expressing cells and in rat spinal cord slice cultures exposed to NMO anti-AQP4 autoantibody (AQP4-IgG) and complement, with >500-fold greater potency than IVIG or monomeric Fc fragments. Fc hexamers at low concentration also prevented antibody-dependent cellular cytotoxicity produced by AQP4-IgG and natural killer cells. Serum from rats administered a single intravenous dose of Fc hexamers at 50 mg/kg taken at 8 h did not produce complement-dependent cytotoxicity when added to AQP4-IgG-treated AQP4-expressing cell cultures. In an experimental rat model of NMO produced by intracerebral injection of AQP4-IgG, Fc hexamers at 50 mg/kg administered before and at 12 h after AQP4-IgG fully prevented astrocyte injury, complement activation, inflammation and demyelination. These results support the potential therapeutic utility of recombinant IgG1 Fc hexamers in AQP4-IgG seropositive NMO. Copyright © 2018 Elsevier Ltd. All rights reserved.

  18. Evaluation of Standard and Modified M-FC, MacConkey, and Teepol Media for Membrane Filtration Counting of Fecal Coliforms in Water

    OpenAIRE

    Grabow, W. O. K.; Hilner, C. A.; Coubrough, P.

    1981-01-01

    MacConkey agar, standard M-FC agar, M-FC agar without rosolic acid, M-FC agar with a resuscitation top layer, Teepol agar, and pads saturated with Teepol broth, were evaluated as growth media for membrane filtration counting of fecal coliform bacteria in water. In comparative tests on 312 samples of water from a wide variety of sources, including chlorinated effluents, M-FC agar without rosolic acid proved the medium of choice because it generally yielded the highest counts, was readily obtai...

  19. Estimate of the soil water retention curve from the sorptivity and β parameter calculated from an upward infiltration experiment

    Science.gov (United States)

    Moret-Fernández, D.; Latorre, B.

    2017-01-01

    The water retention curve (θ(h)), which defines the relationship between the volumetric water content (θ) and the matric potential (h), is of paramount importance to characterize the hydraulic behaviour of soils. Because current methods to estimate θ(h) are, in general, tedious and time consuming, alternative procedures to determine θ(h) are needed. Using an upward infiltration curve, the main objective of this work is to present a method to determine the parameters of the van Genuchten (1980) water retention curve (α and n) from the sorptivity (S) and the β parameter defined in the 1D infiltration equation proposed by Haverkamp et al. (1994). The first specific objective is to present an equation, based on the Haverkamp et al. (1994) analysis, which allows describing an upward infiltration process. Secondary, assuming a known saturated hydraulic conductivity, Ks, calculated on a finite soil column by the Darcy's law, a numerical procedure to calculate S and β by the inverse analysis of an exfiltration curve is presented. Finally, the α and n values are numerically calculated from Ks, S and β. To accomplish the first specific objective, cumulative upward infiltration curves simulated with HYDRUS-1D for sand, loam, silt and clay soils were compared to those calculated with the proposed equation, after applying the corresponding β and S calculated from the theoretical Ks, α and n. The same curves were used to: (i) study the influence of the exfiltration time on S and β estimations, (ii) evaluate the limits of the inverse analysis, and (iii) validate the feasibility of the method to estimate α and n. Next, the θ(h) parameters estimated with the numerical method on experimental soils were compared to those obtained with pressure cells. The results showed that the upward infiltration curve could be correctly described by the modified Haverkamp et al. (1994) equation. While S was only affected by early-time exfiltration data, the β parameter had a

  20. Upward Bound: An Untapped Fountain Of Youth Wanting To Learn About Math And Science

    Science.gov (United States)

    Gillis-Davis, J. J.; Sherman, S. B.; Gillis-Davis, L. C.; Svelling, K. L.

    2009-12-01

    We developed a two-phased curricula aimed at high school students in Hawaii’s Upward Bound (UB) programs. The course, called “Tour Through the Solar System”, was tested in the summer 2008-2009 programs of two of the four Hawaii UB programs. Authorized by Congress in 1965, UB is a federal program funded by the U.S. Department of Education to serve students underrepresented in higher education. Students enrolled in UB are predominantly low income, or from families in which neither parent holds a bachelor’s degree. UB programs make a measurable improvement in retaining high school students in the education pipeline in part by using innovative educational and outreach programs to spark students’ interest in learning while building academic self-confidence. Curricula developed for UB are sustainable because there are 964 programs in the United States, and U territories. Education and outreach products can be presented at regional and national meetings, which directors of the UB programs attend. Broad regulations and varied instruction formats allow curriculum developers a flexible and creative framework for developing classes. For instance, regulations stipulate that programs must provide participants with academic instruction in mathematics, laboratory sciences, composition, literature, and foreign languages in preparation for college entrance. UB meets these guidelines through school-year academic activities and a six-week summer school program. In designing our curricula the primary goals were to help students learn how to learn and encourage them to develop an interest in the fields of science, technology, engineering and math using NASA planetary data sets in a Problem-Based Learning (PBL) environment. Our focus on planetary science stems from our familiarity with the data sets, our view that NASA data sets are a naturally inspirational tool to engage high school students, and its cross-disciplinary character: encompassing geology, chemistry, astronomy

  1. Generation of CMAHKO/GTKO/shTNFRI-Fc/HO-1 quadruple gene modified pigs.

    Science.gov (United States)

    Kim, Geon A; Lee, Eun Mi; Jin, Jun-Xue; Lee, Sanghoon; Taweechaipaisankul, Anukul; Hwang, Jong Ik; Alam, Zahid; Ahn, Curie; Lee, Byeong Chun

    2017-08-01

    As an alternative source of organs for transplantation into humans, attention has been directed to pigs due to their similarities in biological features and organ size. However, severe immune rejection has prevented successful xenotransplantation using pig organs and tissues. To overcome immune rejection, recently developed genetic engineering systems such as TALEN coupled with somatic cell nuclear transfer (SCNT) to make embryos could be used to produce pigs compatible with xenotransplantation. We used the TALEN system to target the non-Gal antigen cytidine monophosphate-N-acetylneuraminic acid hydroxylase (CMAH) gene in pigs that is naturally deleted in humans. Gal-deleted cells expressing both soluble human tumor necrosis factor receptor I IgG 1 -Fc (shTNFRI-Fc) and human hemagglutinin -tagged-human heme oxygenase-1 (hHO-1) were transfected with a TALEN target for CMAH. Cells lacking CMAH were negatively selected using N-glyconeuraminic acid (Neu5Gc)/magnetic beads and the level of Neu5Gc expression of isolated cells were analyzed by FACS and DNA sequencing. Cloned embryos using 3 different genetically modified cell clones were respectively transferred into 3 recipients, with 55.6% (5/9) becoming pregnant and three cloned pigs were produced. Successful genetic disruption of the CMAH gene was confirmed by sequencing, showing lack of expression of CMAH in tail-derived fibroblasts of the cloned piglets. Besides decreased expression of Neu5Gc in piglets produced by SCNT, antibody-mediated complement-dependent cytotoxicity assays and natural antibody binding for examining immuno-reactivity of the quadruple gene modified pigs derived from endothelial cells and fibroblasts were reduced significantly compared to those of wild type animals. We conclude that by combining the TALEN system and transgenic cells, targeting of multiple genes could be useful for generating organs for xenotransplantation. We produced miniature pigs with quadruple modified genes CMAHKO/GTKO/shTNFRI-Fc

  2. Neutron flux monitoring device

    International Nuclear Information System (INIS)

    Goto, Yasushi; Mitsubori, Minehisa; Ohashi, Kazunori.

    1997-01-01

    The present invention provides a neutron flux monitoring device for preventing occurrence of erroneous reactor scram caused by the elevation of the indication of a start region monitor (SRM) due to a factor different from actual increase of neutron fluxes. Namely, judgement based on measured values obtained by a pulse counting method and a judgment based on measured values obtained by a Cambel method are combined. A logic of switching neutron flux measuring method to be used for monitoring, namely, switching to an intermediate region when both of the judgements are valid is adopted. Then, even if the indication value is elevated based on the Cambel method with no increase of the counter rate in a neutron source region, the switching to the intermediate region is not conducted. As a result, erroneous reactor scram such as 'shorter reactor period' can be avoided. (I.S.)

  3. FC Kliini RY:n Kesäpäivien suunnittelu ja järjestäminen

    OpenAIRE

    Narmala, Kalle

    2012-01-01

    Opinnäytetyön aiheena oli suunnitella ja järjestää FC Kliini ry:n Kesäpäivät. Tapahtuma suunniteltiin yhdistyksen puheenjohtaja Antti Niemisen toimeksiannon mukaan. Kesäpäivien suunnittelu alkoi maaliskuussa 2012, jolloin sen ajankohdaksi päätettiin 17.-19.8.2012. Tapahtuma järjestettiin loppukesästä, jotta kaikki yhdistyksen jäsenet voisivat ottaa osaa tapahtumaan. Opinnäytetyö suoritettiin toiminnallisena, jossa yhdistyy käytäntö sekä teoria. FC Kliini ry on jo kauan suunnitellut virkist...

  4. The etiology of multiple sclerosis: genetic evidence for the involvement of the human endogenous retrovirus HERV-Fc1

    DEFF Research Database (Denmark)

    Nexø, Bjørn Andersen; Christensen, Tove; Frederiksen, Jette

    2011-01-01

    or almost-intact genes. We found that SNPs in the gene TRIM5 were inversely correlated with disease. Conversely, SNPs around one retroviral locus, HERV-Fc1, showed a highly significant association with disease. The latter association was limited to a narrow region that contains no other known genes. We...... conclude that HERV-Fc1 and TRIM5 play a role in the etiology of multiple sclerosis. If these results are confirmed, they point to new modes of treatment for multiple sclerosis....

  5. Atmospheric neutrino fluxes

    International Nuclear Information System (INIS)

    Honda, M.; Kasahara, K.; Hidaka, K.; Midorikawa, S.

    1990-02-01

    A detailed Monte Carlo simulation of neutrino fluxes of atmospheric origin is made taking into account the muon polarization effect on neutrinos from muon decay. We calculate the fluxes with energies above 3 MeV for future experiments. There still remains a significant discrepancy between the calculated (ν e +antiν e )/(ν μ +antiν μ ) ratio and that observed by the Kamiokande group. However, the ratio evaluated at the Frejus site shows a good agreement with the data. (author)

  6. Magnetic Flux Conversion in the DIII-D Steady-State Hybrid Scenario

    Science.gov (United States)

    Taylor, N. Z.; Luce, T. C.; La Haye, R. J.; Petty, C. C.; Nazikian, R.

    2017-10-01

    The hybrid is a promising high confinement scenario for ITER. The broader current profile aids discharge sustainment by raising qmin > 1 thereby avoiding sawtooth-triggered 2/1 tearing modes. In DIII-D hybrid scenario discharges, the rate of poloidal magnetic energy consumption is more than the rate of energy flow from the poloidal field coils. This is evidence that there is a conversion of toroidal flux to poloidal flux, which may be responsible for the anomalous broadening of the current profile known as flux pumping. The rate of poloidal flux being provided and consumed was tracked with coil and kinetic flux states. During long stationary intervals (1.5 seconds) with constant stored magnetic energy, a significant flux state deficit rate >10 mV was observed. The inequality in the evolution of the flux states was observed in hybrids that were 100% non-inductive and with successful RMP ELM suppression. Work supported by the US DOE under DE-FC02-04ER54698 and DE-AC05-06OR23100.

  7. Dal castrum altomedievale al restauro settecentesco: storia e archeologia del castello di Sorrivoli (Roncofreddo - FC

    Directory of Open Access Journals (Sweden)

    Fiorini, Andrea

    2011-12-01

    Full Text Available The methods and tools used to determine the history of construction and building techniques of the castle of Sorrivoli (Roncofreddo - FC are here described. This is a research project carried out within a study coordinated by the teaching of Medieval Archaeology (University of Bologna, which has the purpose of conducting a census of all the medieval castles in Romagna. There is certain news from the tenth century concerning the castle to be studied. However, the investigations have shown that the standing preserved structures must be dated from the fourteenth century onwards. The system of photogrammetric survey of the walls and the technique of threedimensional modelling of the structures are here described. An extended part of this paper is also devoted to results of stratigraphic, typological, geological, metrological and comparative mensio-cronological analysis.No disponible

  8. New national conversion line for Bactoscan FC in Italy: A step forward

    Directory of Open Access Journals (Sweden)

    G. Bolzoni

    2015-06-01

    Full Text Available To improve the reproducibility of flow cytometry technique for total bacterial count in milk, a conversion from instrumental results (impulses/μL to the reference method resultes (cfu/mL is needed. In 2008 in Italy, a project for a common conversion line for Bactoscan FC was initiated.In this paper we report on the second phase of the project focusing on the statistical procedure used to evaluate the validity of the data. The new conversion line, representative of national milk(2,732 valid samples from 29 labs obtained from both rounds of the study is: Log10 (cfu mL-1 = Log10 (IBC μL-1 x 0.939 + 2.559, with S y:x= 0.282 with an application range up to 70,000 IBC μL-1.

  9. Therapeutic Fc-fusion proteins and peptides as successful alternatives to antibodies.

    Science.gov (United States)

    Beck, Alain; Reichert, Janice M

    2011-01-01

    Therapeutic antibodies have captured substantial attention due to the relatively high rate at which these products reach marketing approval, and the subsequent commercial success they frequently achieve. In the 2000s, a total of 20 antibodies (18 full-length IgG and 2 Fab) were approved by the Food and Drug Administration (FDA) or European Medicines Agency (EMA). In the 2010s to date, an additional 3 antibodies (denosumab, belimumab, ipilimumab) have been approved and one antibody-drug conjugate (brentuximab vedotin) is undergoing regulatory review and may be approved in the US by August 30, 2011. However, a less heralded group of antibody-based therapeutics comprising proteins or peptides fused with an Fc is following the success of classical antibodies.

  10. Protein engineering and the use of molecular modeling and simulation: the case of heterodimeric Fc engineering.

    Science.gov (United States)

    Spreter Von Kreudenstein, Thomas; Lario, Paula I; Dixit, Surjit B

    2014-01-01

    Computational and structure guided methods can make significant contributions to the development of solutions for difficult protein engineering problems, including the optimization of next generation of engineered antibodies. In this paper, we describe a contemporary industrial antibody engineering program, based on hypothesis-driven in silico protein optimization method. The foundational concepts and methods of computational protein engineering are discussed, and an example of a computational modeling and structure-guided protein engineering workflow is provided for the design of best-in-class heterodimeric Fc with high purity and favorable biophysical properties. We present the engineering rationale as well as structural and functional characterization data on these engineered designs. Copyright © 2013 Elsevier Inc. All rights reserved.

  11. Social Media Strategy in Professional Football: The case of Liverpool FC

    Directory of Open Access Journals (Sweden)

    Petros Parganas

    2015-10-01

    Full Text Available The purpose of this study is to examine the role of social media as marketing tools in professional team sport organizations. Focusing on the English Premier League football club Liverpool FC, an exploratory case study design using one-to-one inter- views with the club’s senior social media managers was adopt- ed. The findings highlight the need for integration of all media channels of the club in order to allow for a more targeted and engaging approach towards its fans, and suggests that further development of social media strategies has potential to deliver increased commercial gains both in the short and in the long term. However, given the peculiar nature of sports fandom, a major issue for social media managers is to find the appropriate balance between content that increases fan interaction and engagement and content that deals with purely commercial purposes.

  12. Final Report for DOE Project DE-FC07-99CH11010

    Energy Technology Data Exchange (ETDEWEB)

    Jed Randall; Robert Kean

    2003-10-22

    Department of Energy award number DE-FC07-99CH11010, Enhanced Utilization of Corn Based Biomaterials, supported a technology development program sponsored by Cargill Dow LLC from September 30, 1999 through June 30, 2003. The work involved fundamental scientific studies on poly lactic acid (PLA), a new environmentally benign plastic material from renewable resources. DOE funds supported academic research at the Colorado School of Mines and the National Renewable Energy Laboratory (NREL), and industry cost share was directed towards applied research into new product development utilizing the fundamental information generated by the academic partners. Under the arrangement of the grant, the fundamental information is published so that other companies can utilize it in evaluating the applicability of PLA in their own products. The overall project objective is to increase the utilization of PLA, a renewable resource based plastic, currently produced from fermented corn sugar.

  13. Optimal economic dispatch of FC-CHP based heat and power micro-grids

    International Nuclear Information System (INIS)

    Nazari-Heris, Morteza; Abapour, Saeed; Mohammadi-Ivatloo, Behnam

    2017-01-01

    Highlights: • The multi objective economic/environmental heat and power MG dispatch is solved. • The heat and power MG include FC, CHP, boiler, storage system, and heat buffer tank. • Multi objective scheduling of heat and power MG is solved using ε-constraint method. • DR program is employed in the stochastic programming of heat and power MG dispatch. • The uncertainties for load demand and price signals are taken into account. - Abstract: Micro-grids (MGs) are introduced as a solution for distributed energy resource (DER) units and energy storage systems (ESSs) to participate in providing the required electricity demand of controllable and non-controllable loads. In this paper, the authors study the short-term scheduling of grid-connected industrial heat and power MG which contains a fuel cell (FC) unit, combined heat and power (CHP) generation units, power-only unit, boiler, battery storage system, and heat buffer tank. The paper is aimed to solve the multi-objective MG dispatch problem containing cost and emission minimization with the considerations of demand response program and uncertainties. A probabilistic framework based on a scenario method, which is considered for load demand and price signals, is employed to overcome the uncertainties in the optimal energy management of the MG. In order to reduce operational cost, time-of-use rates of demand response programs have been modeled, and the effects of such programs on the load profile have been discussed. To solve the multi-objective optimization problem, the ε-constraint method is used and a fuzzy satisfying approach has been employed to select the best compromise solution. Three cases are studied in this research to confirm the performance of the proposed method: islanded mode, grid-connected mode, and the impact of time of the use-demand response program on MG scheduling.

  14. Model-based investigation of intracellular processes determining antibody Fc-glycosylation under mild hypothermia.

    Science.gov (United States)

    Sou, Si Nga; Jedrzejewski, Philip M; Lee, Ken; Sellick, Christopher; Polizzi, Karen M; Kontoravdi, Cleo

    2017-07-01

    Despite the positive effects of mild hypothermic conditions on monoclonal antibody (mAb) productivity (q mAb ) during mammalian cell culture, the impact of reduced culture temperature on mAb Fc-glycosylation and the mechanism behind changes in the glycan composition are not fully established. The lack of knowledge about the regulation of dynamic intracellular processes under mild hypothermia restricts bioprocess optimization. To address this issue, a mathematical model that quantitatively describes Chinese hamster ovary (CHO) cell behavior and metabolism, mAb synthesis and mAb N-linked glycosylation profile before and after the induction of mild hypothermia is constructed. Results from this study show that the model is capable of representing experimental results well in all of the aspects mentioned above, including the N-linked glycosylation profile of mAb produced under mild hypothermia. Most importantly, comparison between model simulation results for different culture temperatures suggests the reduced rates of nucleotide sugar donor production and galactosyltransferase (GalT) expression to be critical contributing factors that determine the variation in Fc-glycan profiles between physiological and mild hypothermic conditions in stable CHO transfectants. This is then confirmed using experimental measurements of GalT expression levels, thereby closing the loop between the experimental and the computational system. The identification of bottlenecks within CHO cell metabolism under mild hypothermic conditions will aid bioprocess optimization, for example, by tailoring feeding strategies to improve NSD production, or manipulating the expression of specific glycosyltransferases through cell line engineering. Biotechnol. Bioeng. 2017;114: 1570-1582. © 2016 The Authors. Biotechnology and Bioengineering Published by Wiley Periodicals Inc. © 2016 The Authors. Biotechnology and Bioengineering Published by Wiley Periodicals Inc.

  15. Eddy covariance flux measurements of biogenic VOCs during ECHO 2003 using proton transfer reaction mass spectrometry

    Directory of Open Access Journals (Sweden)

    C. Spirig

    2005-01-01

    Full Text Available Within the framework of the AFO 2000 project ECHO, two PTR-MS instruments were operated in combination with sonic anemometers to determine biogenic VOC fluxes from a mixed deciduous forest site in North-Western Germany. The measurement site was characterised by a forest of inhomogeneous composition, complex canopy structure, limited extension in certain wind directions and frequent calm wind conditions during night time. The eddy covariance (EC technique was applied since it represents the most direct flux measurement approach on the canopy scale and is, therefore, least susceptible to these non-ideal conditions. A specific flux calculation method was used to account for the sequential multi-component PTR-MS measurements and allowing an individual delay time adjustment as well as a rigorous quality control based on cospectral analysis. The validated flux results are consistent with light and temperature dependent emissions of isoprene and monoterpenes from this forest, with average daytime emissions of 0.94 and 0.3µg m-2s-1, respectively. Emissions of methanol reached on average 0.087µg m-2s-1 during daytime, but fluxes were too small to be detected during night time. Upward fluxes of the isoprene oxidation products methyl vinyl ketone (MVK and methacrolein (MACR were also found, being two orders of magnitude lower than those of isoprene. Calculations with an analytical footprint model indicate that the observed isoprene fluxes correlate with the fraction of oaks within the footprints of the flux measurement.

  16. How Upward Moral Comparison Influences Prosocial Behavioral Intention: Examining the Mediating Role of Guilt and the Moderating Role of Moral Identity

    Directory of Open Access Journals (Sweden)

    Heyun Zhang

    2017-09-01

    Full Text Available Although it has been shown that exceptional good deeds exert influences on people's prosocial behavior and intention, we have known little about how common moral actions in our daily life. The present study aimed to examine how upward moral comparison influenced prosocial behavioral intention as well as to explore the mediating role of guilt and the moderating role of moral identity in the focal relationship. An experimental study was conducted with 162 Chinese undergraduates (103 women, 59 men randomly assigned to an upward moral comparison condition, an upward competence comparison condition or a control condition. Results indicated that participants in the upward moral comparison condition experienced higher levels of guilt and exhibited stronger motivation to act prosocially, relative to participants in the other two conditions. That is to say, upward moral comparison induces guilty experience, and then increases people's prosocial behavioral intention. Moreover, we have found that moral identity internalization moderates the upward moral comparison-guilt relationship, and the indirect effect of upward moral comparison on prosocial behavioral intention via guilt. The implications of these findings were discussed.

  17. How Upward Moral Comparison Influences Prosocial Behavioral Intention: Examining the Mediating Role of Guilt and the Moderating Role of Moral Identity.

    Science.gov (United States)

    Zhang, Heyun; Chen, Sisi; Wang, Rong; Jiang, Jiang; Xu, Yan; Zhao, Huanhuan

    2017-01-01

    Although it has been shown that exceptional good deeds exert influences on people's prosocial behavior and intention, we have known little about how common moral actions in our daily life. The present study aimed to examine how upward moral comparison influenced prosocial behavioral intention as well as to explore the mediating role of guilt and the moderating role of moral identity in the focal relationship. An experimental study was conducted with 162 Chinese undergraduates (103 women, 59 men) randomly assigned to an upward moral comparison condition, an upward competence comparison condition or a control condition. Results indicated that participants in the upward moral comparison condition experienced higher levels of guilt and exhibited stronger motivation to act prosocially, relative to participants in the other two conditions. That is to say, upward moral comparison induces guilty experience, and then increases people's prosocial behavioral intention. Moreover, we have found that moral identity internalization moderates the upward moral comparison-guilt relationship, and the indirect effect of upward moral comparison on prosocial behavioral intention via guilt. The implications of these findings were discussed.

  18. How Upward Moral Comparison Influences Prosocial Behavioral Intention: Examining the Mediating Role of Guilt and the Moderating Role of Moral Identity

    Science.gov (United States)

    Zhang, Heyun; Chen, Sisi; Wang, Rong; Jiang, Jiang; Xu, Yan; Zhao, Huanhuan

    2017-01-01

    Although it has been shown that exceptional good deeds exert influences on people's prosocial behavior and intention, we have known little about how common moral actions in our daily life. The present study aimed to examine how upward moral comparison influenced prosocial behavioral intention as well as to explore the mediating role of guilt and the moderating role of moral identity in the focal relationship. An experimental study was conducted with 162 Chinese undergraduates (103 women, 59 men) randomly assigned to an upward moral comparison condition, an upward competence comparison condition or a control condition. Results indicated that participants in the upward moral comparison condition experienced higher levels of guilt and exhibited stronger motivation to act prosocially, relative to participants in the other two conditions. That is to say, upward moral comparison induces guilty experience, and then increases people's prosocial behavioral intention. Moreover, we have found that moral identity internalization moderates the upward moral comparison-guilt relationship, and the indirect effect of upward moral comparison on prosocial behavioral intention via guilt. The implications of these findings were discussed. PMID:28959221

  19. A Development of Technical Specification of a Research Reactor with Plate Fuels Cooled by Upward Flow

    International Nuclear Information System (INIS)

    Park, Sujin; Kim, Jeongeun; Kim, Hyeonil

    2016-01-01

    The contents of the TS(Technical Specifications) are definitions, safety limits, limiting safety system settings, limiting conditions for operation, surveillance requirements, design features, and administrative controls. TS for Nuclear Power Plants (NPPs) have been developed since many years until now. On the other hands, there are no applicable modernized references of TS for research reactors with many differences from NPPs in purpose and characteristics. Fuel temperature and Departure from Nuclear Boiling Ratio (DNBR) are being used as references from the thermal-hydraulic analysis point of view for determining whether the design of research reactors satisfies acceptance criteria for the nuclear safety or not. Especially for research reactors using plate-type fuels, fuel temperature and critical heat flux, however, are very difficult to measure during the reactor operation. This paper described the outline of main contents of a TS for open-pool research reactor with plate-type fuels using core cooling through passive systems, where acceptance criteria for nuclear safety such as CHF and fuel temperature cannot be directly measured, different from circumstances in NPPs. Thus, three independent variables instead of non-measurable acceptance criteria: fuel temperature and CHF are considered as safety limits, i.e., power, flow, and flow temperature

  20. Radiation flux measuring device

    International Nuclear Information System (INIS)

    Corte, E.; Maitra, P.

    1977-01-01

    A radiation flux measuring device is described which employs a differential pair of transistors, the output of which is maintained constant, connected to a radiation detector. Means connected to the differential pair produce a signal representing the log of the a-c component of the radiation detector, thereby providing a signal representing the true root mean square logarithmic output. 3 claims, 2 figures

  1. Soluble organic nutrient fluxes

    Science.gov (United States)

    Robert G. Qualls; Bruce L. Haines; Wayne Swank

    2014-01-01

    Our objectives in this study were (i) compare fluxes of the dissolved organic nutrients dissolved organic carbon (DOC), DON, and dissolved organic phosphorus (DOP) in a clearcut area and an adjacent mature reference area. (ii) determine whether concentrations of dissolved organic nutrients or inorganic nutrients were greater in clearcut areas than in reference areas,...

  2. Flux vacua and supermanifolds

    Energy Technology Data Exchange (ETDEWEB)

    Grassi, Pietro Antonio [CERN, Theory Unit, CH-1211 Geneva, 23 (Switzerland); Marescotti, Matteo [Dipartimento di Fisica Teorica, Universita di Torino, Via Giuria 1, I-10125, Turin (Italy)

    2007-01-15

    As been recently pointed out, physically relevant models derived from string theory require the presence of non-vanishing form fluxes besides the usual geometrical constraints. In the case of NS-NS fluxes, the Generalized Complex Geometry encodes these informations in a beautiful geometrical structure. On the other hand, the R-R fluxes call for supergeometry as the underlying mathematical framework. In this context, we analyze the possibility of constructing interesting supermanifolds recasting the geometrical data and RR fluxes. To characterize these supermanifolds we have been guided by the fact topological strings on supermanifolds require the super-Ricci flatness of the target space. This can be achieved by adding to a given bosonic manifold enough anticommuting coordinates and new constraints on the bosonic sub-manifold. We study these constraints at the linear and non-linear level for a pure geometrical setting and in the presence of p-form field strengths. We find that certain spaces admit several super-extensions and we give a parameterization in a simple case of d bosonic coordinates and two fermionic coordinates. In addition, we comment on the role of the RR field in the construction of the super-metric. We give several examples based on supergroup manifolds and coset supermanifolds.

  3. Flux vacua and supermanifolds

    International Nuclear Information System (INIS)

    Grassi, Pietro Antonio; Marescotti, Matteo

    2007-01-01

    As been recently pointed out, physically relevant models derived from string theory require the presence of non-vanishing form fluxes besides the usual geometrical constraints. In the case of NS-NS fluxes, the Generalized Complex Geometry encodes these informations in a beautiful geometrical structure. On the other hand, the R-R fluxes call for supergeometry as the underlying mathematical framework. In this context, we analyze the possibility of constructing interesting supermanifolds recasting the geometrical data and RR fluxes. To characterize these supermanifolds we have been guided by the fact topological strings on supermanifolds require the super-Ricci flatness of the target space. This can be achieved by adding to a given bosonic manifold enough anticommuting coordinates and new constraints on the bosonic sub-manifold. We study these constraints at the linear and non-linear level for a pure geometrical setting and in the presence of p-form field strengths. We find that certain spaces admit several super-extensions and we give a parameterization in a simple case of d bosonic coordinates and two fermionic coordinates. In addition, we comment on the role of the RR field in the construction of the super-metric. We give several examples based on supergroup manifolds and coset supermanifolds

  4. Atmospheric neutrino fluxes

    International Nuclear Information System (INIS)

    Perkins, D.H.

    1984-01-01

    The atmospheric neutrino fluxes, which are responsible for the main background in proton decay experiments, have been calculated by two independent methods. There are discrepancies between the two sets of results regarding latitude effects and up-down asymmetries, especially for neutrino energies Esub(ν) < 1 GeV. (author)

  5. Flux scaling: Ultimate regime

    Indian Academy of Sciences (India)

    First page Back Continue Last page Overview Graphics. Flux scaling: Ultimate regime. With the Nusselt number and the mixing length scales, we get the Nusselt number and Reynolds number (w'd/ν) scalings: and or. and. scaling expected to occur at extremely high Ra Rayleigh-Benard convection. Get the ultimate regime ...

  6. Is Fc gamma receptor IIA (FcγRIIA) polymorphism associated with clinical malaria and Plasmodium falciparum specific antibody levels in children from Burkina Faso?

    DEFF Research Database (Denmark)

    Cherif, Mariama K; Sanou, Guillaume S; Bougouma, Edith C

    2015-01-01

    In the present study, the influences of FcγRIIA polymorphism on susceptibility to malaria and antibody responses to Plasmodium falciparum antigens were analyzed in children. We recruited 96 healthy children between 3 and 10 years at the beginning of the high transmission season and we followed up...

  7. Downmodulation of Vaccine-Induced Immunity and Protection against the Intracellular Bacterium Francisella tularensis by the Inhibitory Receptor FcγRIIB

    Directory of Open Access Journals (Sweden)

    Brian J. Franz

    2015-01-01

    Full Text Available Fc gamma receptor IIB (FcγRIIB is the only Fc gamma receptor (FcγR which negatively regulates the immune response, when engaged by antigen- (Ag- antibody (Ab complexes. Thus, the generation of Ag-specific IgG in response to infection or immunization has the potential to downmodulate immune protection against infection. Therefore, we sought to determine the impact of FcγRIIB on immune protection against Francisella tularensis (Ft, a Category A biothreat agent. We utilized inactivated Ft (iFt as an immunogen. Naïve and iFt-immunized FcγRIIB knockout (KO or wildtype (WT mice were challenged with Ft-live vaccine strain (LVS. While no significant difference in survival between naïve FcγRIIB KO versus WT mice was observed, iFt-immunized FcγRIIB KO mice were significantly better protected than iFt-immunized WT mice. Ft-specific IgA in serum and bronchial alveolar lavage, as well as IFN-γ, IL-10, and TNF-α production by splenocytes harvested from iFt-immunized FcγRIIB KO, were also significantly elevated. In addition, iFt-immunized FcγRIIB KO mice exhibited a reduction in proinflammatory cytokine levels in vivo at 5 days after challenge, which correlates with increased survival following Ft-LVS challenge in published studies. Thus, these studies demonstrate for the first time the ability of FcγRIIB to regulate vaccine-induced IgA production and downmodulate immunity and protection. The immune mechanisms behind the above observations and their potential impact on vaccine development are discussed.

  8. An investigation on near wall transport characteristics in an adiabatic upward gas-liquid two-phase slug flow

    Science.gov (United States)

    Zheng, Donghong; Che, Defu

    2007-08-01

    The near-wall transport characteristics, inclusive of mass transfer coefficient and wall shear stress, which have a great effect on gas-liquid two-phase flow induced internal corrosion of low alloy pipelines in vertical upward oil and gas mixing transport, have been both mechanistically and experimentally investigated in this paper. Based on the analyses on the hydrodynamic characteristics of an upward slug unit, the mass transfer in the near wall can be divided into four zones, Taylor bubble nose zone, falling liquid film zone, Taylor bubble wake zone and the remaining liquid slug zone; the wall shear stress can be divided into two zones, the positive wall shear stress zone associated with the falling liquid film and the negative wall shear stress zone associated with the liquid slug. Based on the conventional mass transfer and wall shear stress characteristics formulas of single phase liquid full-pipe turbulent flow, corrected normalized mass transfer coefficient formula and wall shear stress formula are proposed. The calculated results are in good agreement with the experimental data. The shear stress and the mass transfer coefficient in the near wall zone are increased with the increase of superficial gas velocity and decreased with the increase of superficial liquid velocity. The mass transfer coefficients in the falling liquid film zone and the wake zone of leading Taylor bubble are lager than those in the Taylor bubble nose zone and the remaining liquid slug zone, and the wall shear stress associated falling liquid film is larger than that associated the liquid slug. The mass transfer coefficient is within 10-3 m/s, and the wall shear stress below 103 Pa. It can be concluded that the alternate wall shear stress due to upward gas-liquid slug flow is considered to be the major cause of the corrosion production film fatigue cracking.

  9. Parallel combination of FC and UC for vehicular power systems using a multi-input converter-based power interface

    International Nuclear Information System (INIS)

    Vural, B.; Erdinc, O.; Uzunoglu, M.

    2010-01-01

    Fuel cells (FC) are widely recognized as one of the most promising technologies to meet future power requirements of vehicular applications. However, a FC system combined with an energy storage system (ESS) can perform better for vehicle propulsion as considering several points. As the additional ESS can fulfill the transient power demand fluctuations, the FC system can be downsized to fit the base power demand without facing peak loads. Besides, braking energy can be recovered by the ESS. Interfacing of traction drive requirements with characteristics and modes of operation of on-board generation units and ESSs calls for suitable power electronic converter configuration. In this paper, a FC/UC hybrid vehicular power system using a multi-input converter-based power interface is proposed. The applied power interface topology ensures the active power sharing and DC link voltage stabilization for the hybrid vehicular system. The mathematical and electrical models of the hybrid vehicular system are developed in detail and simulated using MATLAB (registered) , Simulink (registered) and SimPowerSystems (registered) environments.

  10. Anti-Tumor Necrosis Factor With a Glyco-Engineered Fc-Region Has Increased Efficacy in Mice With Colitis

    NARCIS (Netherlands)

    Bloemendaal, Felicia M.; Levin, Alon D.; Wildenberg, Manon E.; Koelink, Pim J.; Mcrae, Bradford L.; Salfeld, Jochen; Lum, Jenifer; van der Neut Kolfschoten, Marijn; Claassens, Jill W.; Visser, Remco; Bentlage, Arthur; D'Haens, Geert R. A. M.; Verbeek, J. Sjef; Vidarsson, Gestur; van den Brink, Gijs R.

    2017-01-01

    Although tumor necrosis factor (TNF) antagonists reduce many clinical features of inflammatory bowel disease, complete mucosal healing occurs in fewer than 50% of patients. The Fc-region of monoclonal antibodies against TNF has immunosuppressive properties via effects on macrophage polarization. We

  11. Parallel combination of FC and UC for vehicular power systems using a multi-input converter-based power interface

    Energy Technology Data Exchange (ETDEWEB)

    Vural, B.; Erdinc, O.; Uzunoglu, M. [Department of Electrical Engineering, Yildiz Technical University, Istanbul 34349 (Turkey)

    2010-12-15

    Fuel cells (FC) are widely recognized as one of the most promising technologies to meet future power requirements of vehicular applications. However, a FC system combined with an energy storage system (ESS) can perform better for vehicle propulsion as considering several points. As the additional ESS can fulfill the transient power demand fluctuations, the FC system can be downsized to fit the base power demand without facing peak loads. Besides, braking energy can be recovered by the ESS. Interfacing of traction drive requirements with characteristics and modes of operation of on-board generation units and ESSs calls for suitable power electronic converter configuration. In this paper, a FC/UC hybrid vehicular power system using a multi-input converter-based power interface is proposed. The applied power interface topology ensures the active power sharing and DC link voltage stabilization for the hybrid vehicular system. The mathematical and electrical models of the hybrid vehicular system are developed in detail and simulated using MATLAB registered, Simulink registered and SimPowerSystems registered environments. (author)

  12. Association of variation in Fc gamma receptor 3B gene copy number with rheumatoid arthritis in Caucasian samples

    NARCIS (Netherlands)

    McKinney, Cushla; Fanciulli, Manuela; Merriman, Marilyn E.; Phipps-Green, Amanda; Alizadeh, Behrooz Z.; Koeleman, Bobby P. C.; Dalbeth, Nicola; Gow, Peter J.; Harrison, Andrew A.; Highton, John; Jones, Peter B.; Stamp, Lisa K.; Steer, Sophia; Barrera, Pilar; Coenen, Marieke J. H.; Franke, Barbara; van Riel, Piet L. C. M.; Vyse, Tim J.; Aitman, Tim J.; Radstake, Timothy R. D. J.; Merriman, Tony R.

    2010-01-01

    Objective There is increasing evidence that variation in gene copy number (CN) influences clinical phenotype. The low-affinity Fc gamma receptor 3B (FCGR3B) located in the FCGR gene cluster is a CN polymorphic gene involved in the recruitment to sites of inflammation and activation of

  13. Studies to Prevent Degradation of Recombinant Fc-Fusion Protein Expressed in Mammalian Cell Line and Protein Characterization

    Directory of Open Access Journals (Sweden)

    Sanjukta Chakrabarti

    2016-06-01

    Full Text Available Clipping of recombinant proteins is a major issue in animal cell cultures. A recombinant Fc-fusion protein, VEGFR1(D1–D3-Fc expressed in CHOK1SV GS-KO cells was observed to be undergoing clippings in lab scale cultures. Partial cleaving of expressed protein initiated early on in cell culture and was observed to increase over time in culture and also on storage. In this study, a few parameters were explored in a bid to inhibit clipping in the fusion protein The effects of culture temperature, duration of culture, the addition of an anti-clumping agent, ferric citrate and use of protease inhibitor cocktail on inhibition of proteolysis of the Fc fusion were studied. Lowering of culture temperature from 37 to 30 °C alone appears to be the best solution for reducing protein degradation from the quality, cost and regulatory points of view. The obtained Fc protein was characterized and found to be in its stable folded state, exhibiting a high affinity for its ligand and also biological and functional activities.

  14. Basophil FcεRI Expression in Chronic Spontaneous Urticaria: A Potential Immunological Predictor of Response to Omalizumab Therapy

    Directory of Open Access Journals (Sweden)

    Gustavo Deza

    2017-03-01

    Full Text Available Although the efficacy of omalizumab has been clearly demonstrated in the treatment of chronic spontaneous urticaria (CSU, its mechanism of action, which results in improvement in CSU symptoms, is not entirely understood. This study investigated the effect of omalizumab on expression of the high-affinity IgE receptor (FcεRI on blood basophils from patients with active CSU, and its association with the clinical response. Patients exhibiting significant clinical improvement showed a sharp reduction in the levels of basophil FcεRI after 4 weeks, which was maintained throughout the total duration of the treatment. Such evolution was not observed in non-responder patients. Furthermore, non-responders showed significantly lower baseline levels of FcεRI than responders. Baseline basophil FcεRI expression was found to be a potential immunological predictor of response to omalizumab (100% sensitivity and 73.2% specificity. The results of this study contribute to our knowledge of the therapeutic benefit and mechanism of action of anti-IgE therapy in CSU.

  15. A novel TNFα antagonizing peptide-Fc fusion protein designed based on CDRs of TNFα neutralizing monoclonal antibody

    International Nuclear Information System (INIS)

    Qin Weisong; Feng Jiannan; Zhang Wei; Li Yan; Shen, Beifen

    2004-01-01

    The variable regions of antibody molecules bind antigens with high affinity and specificity. The binding sites are imparted largely to the hypervariable portions (i.e., CDRs) of the variable region. Peptides derived from CDRs can bind antigen with similar specificity acting as mimic of antibody and become drug-designing core, although with markedly lower affinity. In order to increase the affinity and bioactivity, in this study, a novel peptide (PT) designed on CDRs of a TNFα neutralizing monoclonal antibody Z12 was linked with Fc fragment of human IgG1. The interaction mode of PT-linker-Fc (PLF) with TNFα was analyzed with computer-guided molecular modeling method. After expression in Escherichia coli and purification, recombinant PT-linker-Fc could bind directly with the TNFα coated on the ELISA plates. Furthermore, PLF could competitively inhibit the binding of Z12 to TNFα and also inhibit the TNFα-induced cytotoxicity on L929 cells. The TNFα antagonizing activity of PLF was significantly higher than that of the free peptide. This study highlights the potential of human Fc to enhance the potency of peptides designed on the CDRs of antibodies and could be useful in developing new TNFα antagonists

  16. Basophil FcεRI Expression in Chronic Spontaneous Urticaria: A Potential Immunological Predictor of Response to Omalizumab Therapy.

    Science.gov (United States)

    Deza, Gustavo; Bertolín-Colilla, Marta; Pujol, Ramon M; Curto-Barredo, Laia; Soto, Dulce; García, Maribel; Hernández, Pilar; Gimeno, Ramon; Giménez-Arnau, Ana M

    2017-06-09

    Although the efficacy of omalizumab has been clearly demonstrated in the treatment of chronic spontaneous urticaria (CSU), its mechanism of action, which results in improvement in CSU symptoms, is not entirely understood. This study investigated the effect of omalizumab on expression of the high-affinity IgE receptor (FcεRI) on blood basophils from patients with active CSU, and its association with the clinical response. Patients exhibiting significant clinical improvement showed a sharp reduction in the levels of basophil FcεRI after 4 weeks, which was maintained throughout the total duration of the treatment. Such evolution was not observed in non-responder patients. Furthermore, non-responders showed significantly lower baseline levels of FcεRI than responders. Baseline basophil FcεRI expression was found to be a potential immunological predictor of response to omalizumab (100% sensitivity and 73.2% specificity). The results of this study contribute to our knowledge of the therapeutic benefit and mechanism of action of anti-IgE therapy in CSU.

  17. BRS FC402: high-yielding common bean cultivar with carioca grain, resistance to anthracnose and fusarium wilt

    Directory of Open Access Journals (Sweden)

    Leonardo Cunha Melo

    2016-12-01

    Full Text Available BRS FC402 is a common bean cultivar of the carioca-grain group with commercial grain quality, suitable for cultivation in 21 Brazilian states. Cultivar has a normal cycle (85-94 days, high yield potential (4479 kg ha-1, 10.1% higher mean yield than the controls (2462 kg ha-1 and resistance to fusarium wilt and anthracnose.

  18. Tumor Cells Express FcγRl Which Contributes to Tumor Cell Growth and a Metastatic Phenotype

    Directory of Open Access Journals (Sweden)

    M. Bud Nelson

    2001-01-01

    Full Text Available High levels of circulating immune complexes containing tumor-associated antigens are associated with a poor prognosis for individuals with cancer. The ability of B cells, previously exposed to tumor-associated antigens, to promote both in vitro and in vivo tumor growth formed the rationale to evaluate the mechanism by which immune complexes may promote tumor growth. In elucidating this mechanism, FcγRl expression by tumor cells was characterized by flow cytometry, polymerase chain reaction, and sequence analysis. Immune complexes containing shed tumor antigen and anti-shed tumor antigen Ab cross-linked FcγRl-expressing tumor cells, which resulted in an induction of tumor cell proliferation and of shed tumor antigen production. Use of selective tyrosine kinase inhibitors demonstrated that tumor cell proliferation induced by immune complex cross-linking of FcγRl is dependent on the tyrosine kinase signal transduction pathway. A selective inhibitor of phosphatidylinositol-3 kinase also inhibited this induction of tumor cell proliferation. These findings support a role for immune complexes and FcγRl expression by tumor cells in augmentation of tumor growth and a metastatic phenotype.

  19. Tracking the maximum efficiency point for the FC system based on extremum seeking scheme to control the air flow

    International Nuclear Information System (INIS)

    Bizon, Nicu

    2014-01-01

    Highlights: • The Maximum Efficiency Point (MEP) is tracked based on air flow rate. • The proposed Extremum Seeking (ES) control assures high performances. • About 10 kW/s search speed and 99.99% stationary accuracy can be obtained. • The energy efficiency increases with 3–12%, according to the power losses. • The control strategy is robust based on self-optimizing ES scheme proposed. - Abstract: An advanced control of the air compressor for the Proton Exchange Membrane Fuel Cell (PEMFC) system is proposed in this paper based on Extremum Seeking (ES) control scheme. The FC net power is mainly depended on the air and hydrogen flow rate and pressure, and heat and water management. This paper proposes to compute the optimal value for the air flow rate based on the advanced ES control scheme in order to maximize the FC net power. In this way, the Maximum Efficiency Point (MEP) will be tracked in real time, with about 10 kW/s search speed and a stationary accuracy of 0.99. Thus, energy efficiency will be close to the maximum value that can be obtained for a given PEMFC stack and compressor group under dynamic load. It is shown that the MEP tracking allows an increasing of the FC net power with 3–12%, depending on the percentage of the FC power supplied to the compressor and the level of the load power. Simulations shows that the performances mentioned above are effective

  20. Association of FcγRIIa R131H polymorphism with idiopathic pulmonary fibrosis severity and progression

    Directory of Open Access Journals (Sweden)

    Hirani Nikhil

    2010-10-01

    Full Text Available Abstract Background A significant genetic component has been described for idiopathic pulmonary fibrosis (IPF. The R131H (rs1801274 polymorphism of the IgG receptor FcγRIIa determines receptor affinity for IgG subclasses and is associated with several chronic inflammatory diseases. We investigated whether this polymorphism is associated with IPF susceptibility or progression. Methods In a case-control study, we compared the distribution of FcγRIIa R131H genotypes in 142 patients with IPF and in 218 controls using allele-specific PCR amplification. Results No differences in the frequency of FcγRIIa genotypes were evident between IPF patients and control subjects. However, significantly impaired pulmonary function at diagnosis was observed in HH compared to RR homozygotes, with evidence of more severe restriction (reduced forced vital capacity (FVC and lower diffusing capacity for carbon monoxide (DLCO. Similarly, increased frequency of the H131 allele was observed in patients with severe disease (DLCO 10% drop in FVC and/or > 15% fall in DLCO at 12 months after baseline (0.48 vs. 0.33; p = 0.023. Conclusions These findings support an association between the FcγRIIa R131H polymorphism and IPF severity and progression, supporting the involvement of immunological mechanisms in IPF pathogenesis.

  1. Increased half-life and enhanced potency of Fc-modified human PCSK9 monoclonal antibodies in primates.

    Directory of Open Access Journals (Sweden)

    Yijun Shen

    Full Text Available Blocking proprotein convertase subtilisin kexin type 9 (PCSK9 binding to low-density lipoprotein receptor (LDLR can profoundly lower plasma LDL levels. Two anti-PCKS9 monoclonal antibodies (mAbs, alirocumab and evolocumab, were approved by the FDA in 2015. The recommended dose is 75 mg to 150 mg every two weeks for alirocumab and 140mg every two weeks or 420 mg once a month for evolocumab. This study attempted to improve the pharmacokinetic properties of F0016A, an IgG1 anti-PCKS9 mAb, to generate biologically superior molecules. We engineered several variants with two or three amino acid substitutions in the Fc fragment based on prior knowledge. The Fc-modified mAbs exhibited increased binding to FcRn, resulting in prolonged serum half-life and enhanced efficacy in vivo. These results demonstrate that Fc-modified anti-PCKS9 antibodies may enable less frequent or lower dosing of antibodies by improved recycling into the blood.

  2. An Fc engineering approach that modulates antibody-dependent cytokine release without altering cell-killing functions.

    Science.gov (United States)

    Kinder, Michelle; Greenplate, Allison R; Strohl, William R; Jordan, Robert E; Brezski, Randall J

    2015-01-01

    Cytotoxic therapeutic monoclonal antibodies (mAbs) often mediate target cell-killing by eliciting immune effector functions via Fc region interactions with cellular and humoral components of the immune system. Key functions include antibody-dependent cell-mediated cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP), and complement-dependent cytotoxicity (CDC). However, there has been increased appreciation that along with cell-killing functions, the induction of antibody-dependent cytokine release (ADCR) can also influence disease microenvironments and therapeutic outcomes. Historically, most Fc engineering approaches have been aimed toward modulating ADCC, ADCP, or CDC. In the present study, we describe an Fc engineering approach that, while not resulting in impaired ADCC or ADCP, profoundly affects ADCR. As such, when peripheral blood mononuclear cells are used as effector cells against mAb-opsonized tumor cells, the described mAb variants elicit a similar profile and quantity of cytokines as IgG1. In contrast, although the variants elicit similar levels of tumor cell-killing as IgG1 with macrophage effector cells, the variants do not elicit macrophage-mediated ADCR against mAb-opsonized tumor cells. This study demonstrates that Fc engineering approaches can be employed to uncouple macrophage-mediated phagocytic and subsequent cell-killing functions from cytokine release.

  3. IgG-Fc-mediated effector functions: molecular definition of interaction sites for effector ligands and the role of glycosylation.

    Science.gov (United States)

    Jefferis, R; Lund, J; Pound, J D

    1998-06-01

    The Fc region of human IgG expresses interaction sites for many effector ligands. In this review the topographical distributions of ten of these sites are discussed in relation to functional requirement. It is apparent that interaction sites localised to the inter-CH2-CH3 domain region of the Fc allow for functional divalency, whereas sites localised to the hinge proximal region of the CH2 domain are functionally monovalent, with expression of the latter sites being particularly dependent on glycosylation. All x-ray crystal structures for Fc and Fc-ligand complexes report that the protein structure of the hinge proximal region of the CH2 domain is "disordered", suggesting "internal mobility". We propose a model in which such "internal mobility" results in the generation of a dynamic equilibrium between multiple conformers, certain of which express interaction sites specific to individual ligands. The emerging understanding of the influence of oligosaccharide/protein interactions on protein conformation and biological function of IgG antibodies suggests a potential to generate novel glycoforms of antibody molecules having unique profiles of effector functions.

  4. Sunspots and the physics of magnetic flux tubes. VI - Convective propulsion. VII - Heat flow in a convective downdraft

    Science.gov (United States)

    Parker, E. N.

    1979-01-01

    The effect of negative aerodynamic drag in an ideal fluid subject to convective instability is considered. It is shown that a cylinder moving in such a fluid is propelled forward in its motion by the convective forces and that the characteristic acceleration time is comparable to the onset time of convective motions in the fluid. It is suggested that convective propulsion plays an important role in the dynamics of flux tubes extending through the surface of the sun. The suppression of the upward heat flow in a Boussinesq convective cell with free upper and lower boundaries by a downdraft is then analyzed. Application to the solar convection zone indicates that downdrafts of 1 to 2 km/s at depths of 1000 to 4000 km beneath the visible surface of the sun are sufficient to reduce the upward heat flux to a small fraction of the ambient value.

  5. Connecting theory to fat talk: body dissatisfaction mediates the relationships between weight discrepancy, upward comparison, body surveillance, and fat talk.

    Science.gov (United States)

    Arroyo, Analisa

    2014-06-01

    The fat talk literature is meager in terms of offering theoretical explanations for women's self-disparaging communication. The research presented here sought to establish a relationship between three prominent body image theories - self-discrepancy theory, social comparison theory, and objectification theory - and fat talk by proposing body dissatisfaction as a potential mediating mechanism. Young adult women (N=201) completed an online questionnaire. As predicted, results revealed that body dissatisfaction significantly mediated the relationships between weight discrepancy, upward comparison, body surveillance and fat talk. Effect size estimates indicated that the size of each indirect effect was medium in magnitude. Copyright © 2014 Elsevier Ltd. All rights reserved.

  6. The invisible minority: revisiting the debate on foreign-accented speakers and upward mobility in the workplace.

    Science.gov (United States)

    Akomolafe, Soji

    2013-01-01

    Of some of the major types of discrimination, the one that gets the least attention is national origin discrimination and in particular, accent discrimination, especially when it comes to upward mobility in the workplace. Yet, unlike other forms of discrimination, accent discrimination is rarely a subject of any robust public debate. This paper is a modest attempt to help establish a framework for understanding the relative neglect to which the discourse on accent discrimination has been subjected vis-a-vis the overall national debate on diversity. Hopefully, in the process, it will stimulate a more robust conversation on the plight of foreign-accented speakers.

  7. Upward Trend in Catalytic Efficiency of Rare-Earth Triflate Catalysts in Friedel-Crafts Aromatic Sulfonylation Reactions

    DEFF Research Database (Denmark)

    Duus, Fritz; Le, Thach Ngoc; Nguyen, Vo Thu An

    2014-01-01

    A series of 14 lanthanide (Ln) triflates were investigated as sustainable catalysts for aromatic sulfonylation reactions under microwave irradiation. The catalytic efficiency of the early triflates La(OTf)3–Eu(OTf)3 is good for long irradiation times. For the later lanthanides, yields reaching over...... 90 % were achieved for short irradiation periods. This was the case especially for Tm(OTf)3, Yb(OTf)3, and Lu(OTf)3, of which Yb(OTf)3 was the most efficient. The upward trend in catalytic efficiency therefore correlates with the lanthanide sequence in the periodic table. The results can be explained...

  8. Corrosion rate of steel embedded in blended Portland and fluid catalytic cracking catalyst residue (FC3R cement mortars

    Directory of Open Access Journals (Sweden)

    Payá, J.

    2008-12-01

    Full Text Available This paper reports on a study of the corrosion levels in steel bars embedded in mortars made with a blend of Portland cement and (0-20% spent fluid catalytic cracking catalyst residue (FC3R, with a variable (0.3-0.7 water/binder (w/b ratio. The specimens were stored in the following conditions: relative humidity of 40, 80 or 100% and CO2 concentrations of 5 and 100%. The steel corrosion rate was measured with polarization resistance techniques. In the absence of aggressive agents, the steel was found to remain duly passivated in mortars with an FC3R content of up to 15% under all the conditions of relative humidity tested. The reinforcement corrosion level in mortars with a w/b ratio of 0.3 and 15% FC3R subjected to accelerated carbonation was similar to the level observed in the unblended Portland cement control mortar.En este trabajo se ha estudiado el nivel de corrosión de barras de acero embebidas en morteros de cemento Portland con relación agua/material cementante (a/mc variable (0,3-0,7, en los que parte del cemento (0-20% se sustituyó por catalizador de craqueo usado (FC3R. Las condiciones de conservación de las probetas elaboradas fueron las siguientes: distintas humedades relativas (40, 80 y 100% y dos concentraciones de CO2 (5 y 100%. La velocidad de corrosión de los aceros se midió mediante la técnica de resistencia de polarización. Se ha podido determinar que, bajo las distintas condiciones de humedad relativa y ausencia de agresivo, los aceros se mantuvieron correctamente pasivados en los morteros con contenidos de FC3R de hasta el 15%. El nivel de corrosión que presenta el refuerzo embebidos en morteros con sustitución de un 15% de cemento por FC3R y relación a/mc 0,3, al ser sometidos a un proceso de carbonatación acelerada, era muy similar al mostrado por el mortero patrón, sin FC3R.

  9. Antibody glycosylation and its impact on the pharmacokinetics and pharmacodynamics of monoclonal antibodies and Fc-fusion proteins.

    Science.gov (United States)

    Liu, Liming

    2015-06-01

    Understanding the impact of glycosylation and keeping a close control on glycosylation of product candidates are required for both novel and biosimilar monoclonal antibodies (mAbs) and Fc-fusion protein development to ensure proper safety and efficacy profiles. Most therapeutic mAbs are of IgG class and contain a glycosylation site in the Fc region at amino acid position 297 and, in some cases, in the Fab region. For Fc-fusion proteins, glycosylation also frequently occurs in the fusion partners. Depending on the expression host, glycosylation patterns in mAb or Fc-fusions can be significantly different, thus significantly impacting the pharmacokinetics (PK) and pharmacodynamics (PD) of mAbs. Glycans that have a major impact on PK and PD of mAb or Fc-fusion proteins include mannose, sialic acids, fucose (Fuc), and galactose (Gal). Mannosylated glycans can impact the PK of the molecule, leading to reduced exposure and potentially lower efficacy. The level of sialic acid, N-acetylneuraminic acid (NANA), can also have a significant impact on the PK of Fc-fusion molecules. Core Fuc in the glycan structure reduces IgG antibody binding to IgG Fc receptor IIIa relative to IgG lacking Fuc, resulting in decreased antibody-dependent cell-mediated cytotoxicity (ADCC) activities. Glycoengineered Chinese hamster ovary (CHO) expression systems can produce afucosylated mAbs that have increased ADCC activities. Terminal Gal in a mAb is important in the complement-dependent cytotoxicity (CDC) in that lower levels of Gal reduce CDC activity. Glycans can also have impacts on the safety of mAb. mAbs produced in murine myeloma cells such as NS0 and SP2/0 contain glycans such as Galα1-3Galβ1-4N-acetylglucosamine-R and N-glycolylneuraminic acid (NGNA) that are not naturally present in humans and can be immunogenic when used as therapeutics. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

  10. Antigen-Specific IgG ameliorates allergic airway inflammation via Fcγ receptor IIB on dendritic cells

    Directory of Open Access Journals (Sweden)

    Karasuyama Hajime

    2011-04-01

    Full Text Available Abstract Background There have been few reports on the role of Fc receptors (FcRs and immunoglobulin G (IgG in asthma. The purpose of this study is to clarify the role of inhibitory FcRs and antigen presenting cells (APCs in pathogenesis of asthma and to evaluate antigen-transporting and presenting capacity by APCs in the tracheobronchial mucosa. Methods In FcγRIIB deficient (KO and C57BL/6 (WT mice, the effects of intratracheal instillation of antigen-specific IgG were analysed using the model with sensitization and airborne challenge with ovalbumin (OVA. Thoracic lymph nodes instilled with fluorescein-conjugated OVA were analysed by fluorescence microscopy. Moreover, we analysed the CD11c+ MHC class II+ cells which intaken fluorescein-conjugated OVA in thoracic lymph nodes by flow cytometry. Also, lung-derived CD11c+ APCs were analysed by flow cytometry. Effects of anti-OVA IgG1 on bone marrow dendritic cells (BMDCs in vitro were also analysed. Moreover, in FcγRIIB KO mice intravenously transplanted dendritic cells (DCs differentiated from BMDCs of WT mice, the effects of intratracheal instillation of anti-OVA IgG were evaluated by bronchoalveolar lavage (BAL. Results In WT mice, total cells and eosinophils in BAL fluid reduced after instillation with anti-OVA IgG1. Anti-OVA IgG1 suppressed airway inflammation in hyperresponsiveness and histology. In addition, the number of the fluorescein-conjugated OVA in CD11c+ MHC class II+ cells of thoracic lymph nodes with anti-OVA IgG1 instillation decreased compared with PBS. Also, MHC class II expression on lung-derived CD11c+ APCs with anti-OVA IgG1 instillation reduced. Moreover, in vitro, we showed that BMDCs with anti-OVA IgG1 significantly decreased the T cell proliferation. Finally, we demonstrated that the lacking effects of anti-OVA IgG1 on airway inflammation on FcγRIIB KO mice were restored with WT-derived BMDCs transplanted intravenously. Conclusion Antigen-specific IgG ameliorates

  11. Label-free Fab and Fc affinity/avidity profiling of the antibody complex half-life for polyclonal and monoclonal efficacy screening.

    Science.gov (United States)

    Read, Thomas; Olkhov, Rouslan V; Williamson, E Diane; Shaw, Andrew M

    2015-09-01

    A unified approach to affinity screening for Fab and Fc interactions of an antibody for its antigen and FcγR receptor has been developed. An antigen array is used for the Fab affinity and cross-reactivity screening and protein A/G proxy is the FcγR receptor. The affinities are derived using a simple 1:1 binding model with a consistent error analysis. The association and dissociation kinetics are measured over optimised times for accurate determination. The Fab/Fc affinities are derived for ten antibodies: mAb-actin (mouse), pAb-BSA (sheep), pAb-collagen V (rabbit), pAb-CRP (goat), mAb-F1 (mouse), mAbs (mouse) 7.3, 12.3, 29.3, 36.3 and 46.3 raised against LcrV in Yersinia pestis. The rate of the dissociation of antigen-antibody complexes relates directly to their immunological function as does the Fc-FcγR complex and a new half-life plot has been defined with a Fab/Fc half-life range of 17-470 min. The upper half-life value points to surface avidity. Two antibodies that are protective as an immunotherapy define a Fab half-life >250 min and an Fc half-life >50 min as characteristics of ideal interactions which can form the basis of an antibody screen for immunotherapy.

  12. Structural differences between glycosylated, disulfide-linked heterodimeric Knob-into-Hole Fc fragment and its homodimeric Knob-Knob and Hole-Hole side products.

    Science.gov (United States)

    Kuglstatter, A; Stihle, M; Neumann, C; Müller, C; Schaefer, W; Klein, C; Benz, J

    2017-09-01

    An increasing number of bispecific therapeutic antibodies are progressing through clinical development. The Knob-into-Hole (KiH) technology uses complementary mutations in the CH3 region of the antibody Fc fragment to achieve heavy chain heterodimerization. Here we describe the X-ray crystal structures of glycosylated and disulfide-engineered heterodimeric KiH Fc fragment and its homodimeric Knob-Knob and Hole-Hole side products. The heterodimer structure confirms the KiH design principle and supports the hypothesis that glycosylation stabilizes a closed Fc conformation. Both homodimer structures show parallel Fc fragment architectures, in contrast to recently reported crystal structures of the corresponding aglycosylated Fc fragments which in the absence of disulfide mutations show an unexpected antiparallel arrangement. The glycosylated Knob-Knob Fc fragment is destabilized as indicated by variability in the relative orientation of its CH3 domains. The glycosylated Hole-Hole Fc fragment shows an unexpected intermolecular disulfide bond via the introduced Y349C Hole mutation which results in a large CH3 domain shift and a new CH3-CH3 interface. The crystal structures of glycosylated, disulfide-linked KiH Fc fragment and its Knob-Knob and Hole-Hole side products reported here will facilitate further design of highly efficient antibody heterodimerization strategies. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  13. Attenuated atherosclerotic lesions in apoe-fc gamma-chain-deficient hyperlipidemic mouse model is associated with inhibition of Th17 cells and promotion of regulatory T cells

    Science.gov (United States)

    Though the presence of antioxidized low-density lipoprotein IgG is well documented in clinical and animal studies, the role for Fc gamma Rs to the progression of atherosclerosis has not been studied in detail. In the current study, we investigated the role for activating Fc gamma R in the progressio...

  14. Structural insights into the interaction of human IgG1 with FcγRI: no direct role of glycans in binding

    Energy Technology Data Exchange (ETDEWEB)

    Oganesyan, Vaheh, E-mail: oganesyanv@medimmune.com; Mazor, Yariv; Yang, Chunning; Cook, Kimberly E.; Woods, Robert M. [MedImmune LLC, 1 MedImmune Way, Gaithersburg, MD 20878 (United States); Ferguson, Andrew [AstraZeneca Pharmaceuticals, 35 Gatehouse Drive, Mailstop E3, Waltham, MA 02451 (United States); Bowen, Michael A.; Martin, Tom; Zhu, Jie; Wu, Herren; Dall’Acqua, William F., E-mail: oganesyanv@medimmune.com [MedImmune LLC, 1 MedImmune Way, Gaithersburg, MD 20878 (United States)

    2015-10-31

    In an effort to identify the critical structural features responsible for the high-affinity interaction of IgG1 Fc with FcγRI, the structure of the corresponding complex was solved at a resolution of 2.4 Å. The three-dimensional structure of a human IgG1 Fc fragment bound to wild-type human FcγRI is reported. The structure of the corresponding complex was solved at a resolution of 2.4 Å using molecular replacement; this is the highest resolution achieved for an unmutated FcγRI molecule. This study highlights the critical structural and functional role played by the second extracellular subdomain of FcγRI. It also explains the long-known major energetic contribution of the Fc ‘LLGG’ motif at positions 234–237, and particularly of Leu235, via a ‘lock-and-key’ mechanism. Finally, a previously held belief is corrected and a differing view is offered on the recently proposed direct role of Fc carbohydrates in the corresponding interaction. Structural evidence is provided that such glycan-related effects are strictly indirect.

  15. Hybrid IgG4/IgG4 Fc antibodies form upon 'Fab-arm' exchange as demonstrated by SDS-PAGE or size-exclusion chromatography

    NARCIS (Netherlands)

    Rispens, Theo; den Bleker, Tamara H.; Aalberse, Rob C.

    2010-01-01

    Human IgG4 antibodies are dynamic molecules that in vivo exchange half-molecules to become bispecific antibodies. Here we show that IgG4 antibodies and IgG4 Fc fragments similarly exchange resulting in hybrid antibodies (a single Fab + Fc) with a molecular weight of ca. 100 kDa. These antibodies can

  16. Design of a flux buffer based on the flux shuttle

    International Nuclear Information System (INIS)

    Gershenson, M.

    1991-01-01

    This paper discusses the design considerations for a flux buffer based on the flux-shuttle concept. Particular attention is given to the issues of flux popping, stability of operation and saturation levels for a large input. Modulation techniques used in order to minimize 1/f noise, in addition to offsets are also analyzed. Advantages over conventional approaches using a SQUID for a flux buffer are discussed. Results of computer simulations are presented

  17. Prediction of the Pharmacokinetics, Pharmacodynamics, and Efficacy of a Monoclonal Antibody, Using a Physiologically Based Pharmacokinetic FcRn Model

    Science.gov (United States)

    Chetty, Manoranjenni; Li, Linzhong; Rose, Rachel; Machavaram, Krishna; Jamei, Masoud; Rostami-Hodjegan, Amin; Gardner, Iain

    2015-01-01

    Although advantages of physiologically based pharmacokinetic models (PBPK) are now well established, PBPK models that are linked to pharmacodynamic (PD) models to predict pharmacokinetics (PK), PD, and efficacy of monoclonal antibodies (mAbs) in humans are uncommon. The aim of this study was to develop a PD model that could be linked to a physiologically based mechanistic FcRn model to predict PK, PD, and efficacy of efalizumab. The mechanistic FcRn model for mAbs with target-mediated drug disposition within the Simcyp population-based simulator was used to simulate the pharmacokinetic profiles for three different single doses and two multiple doses of efalizumab administered to virtual Caucasian healthy volunteers. The elimination of efalizumab was modeled with both a target-mediated component (specific) and catabolism in the endosome (non-specific). This model accounted for the binding between neonatal Fc receptor (FcRn) and efalizumab (protective against elimination) and for changes in CD11a target concentration. An integrated response model was then developed to predict the changes in mean Psoriasis Area and Severity Index (PASI) scores that were measured in a clinical study as an efficacy marker for efalizumab treatment. PASI scores were approximated as continuous and following a first-order asymptotic progression model. The reported steady state asymptote (Y ss) and baseline score [Y (0)] was applied and parameter estimation was used to determine the half-life of progression (Tp) of psoriasis. Results suggested that simulations using this model were able to recover the changes in PASI scores (indicating efficacy) observed during clinical studies. Simulations of both single dose and multiple doses of efalizumab concentration-time profiles as well as suppression of CD11a concentrations recovered clinical data reasonably well. It can be concluded that the developed PBPK FcRn model linked to a PD model adequately predicted PK, PD, and efficacy of efalizumab. PMID

  18. Altered expression of the TCR signaling related genes CD3 and FcεRIγ in patients with aplastic anemia

    Directory of Open Access Journals (Sweden)

    Li Bo

    2012-03-01

    Full Text Available Abstract Background Aplastic anemia (AA is characterized by pancytopenia and bone marrow hypoplasia, which results from immune-mediated hematopoiesis suppression. Understanding the pathophysiology of the immune system, particularly T cells immunity, has led to improved AA treatment over the past decades. However, primary and secondary failure after immunosuppressive therapy is frequent. Thus, knowledge of the immune mechanisms leading to AA is crucial to fundamentally understand the disease. Findings To elucidate the T cell receptor (TCR signal transduction features in AA, the expression levels of CD3γ, δ, ε and ζ chain and FcεRIγ genes, which are involved in TCR signal transduction, and the negative correlation of the expression levels between the CD3ζ and FcεRIγ genes in T cells from peripheral blood mononuclear cells (PBMCs were analyzed. Real-time RT-PCR using the SYBR Green method was used to detect the expression level of these genes in PBMCs from 18 patients with AA and 14 healthy individuals. The β2microglobulin gene (β2M was used as an endogenous reference. The expression levels of the CD3γ, CD3δ, CD3ε and CD3ζ genes in patients with AA were significantly increased compared to a healthy control group, whereas the FcεRIγ gene expression level was significantly decreased in patients with AA in comparison with the healthy control group. Moreover, the negative correlation of the expression levels between the CD3ζ and FcεRIγ genes was lost. Conclusions To our knowledge, this is the first report of the CD3γ, CD3δ, CD3ε, CD3ζ and FcεRIγ gene expression in patients with AA. The abnormally expressed TCR signaling related genes may relate to T cells dysfunction in AA.

  19. Lobotomy of flux compactifications

    Energy Technology Data Exchange (ETDEWEB)

    Dibitetto, Giuseppe [Institutionen för fysik och astronomi, University of Uppsala,Box 803, SE-751 08 Uppsala (Sweden); Guarino, Adolfo [Albert Einstein Center for Fundamental Physics, Institute for Theoretical Physics,Bern University, Sidlerstrasse 5, CH-3012 Bern (Switzerland); Roest, Diederik [Centre for Theoretical Physics, University of Groningen,Nijenborgh 4 9747 AG Groningen (Netherlands)

    2014-05-15

    We provide the dictionary between four-dimensional gauged supergravity and type II compactifications on T{sup 6} with metric and gauge fluxes in the absence of supersymmetry breaking sources, such as branes and orientifold planes. Secondly, we prove that there is a unique isotropic compactification allowing for critical points. It corresponds to a type IIA background given by a product of two 3-tori with SO(3) twists and results in a unique theory (gauging) with a non-semisimple gauge algebra. Besides the known four AdS solutions surviving the orientifold projection to N=4 induced by O6-planes, this theory contains a novel AdS solution that requires non-trivial orientifold-odd fluxes, hence being a genuine critical point of the N=8 theory.

  20. Supercritical heat transfer correlation for carbon dioxide flowing upward in a vertical tube

    International Nuclear Information System (INIS)

    Mokry, S. J.; Pioro, I. L.; Farah, A.; King, K.

    2010-01-01

    The objective of the current study was to analyze heat-transfer at supercritical conditions using carbon dioxide as a modeling fluid, and to develop a heat-transfer correlation based on data published in open literature. Supercritical (SC) fluids have unique properties. Beyond the critical point (22.1 MPa and 374.1 deg.C for water and 7.38 MPa and 31.0 deg.C for carbon dioxide), the fluid resembles a dense gas. The transition from single-phase liquid to single-phase gas does not involve a distinct phase change under these conditions. Phenomena such as dryout (or critical heat flux) are therefore not relevant. However, at supercritical conditions, deteriorated heat-transfer regime, (i.e., lower Heat Transfer Coefficient (HTC) values, compared to those for the normal or regular heat-transfer regime) may exist. Experiments with Supercritical Water (SCW) are very expensive due to high critical parameters. Therefore, a number of experiments are performed in modeling fluids such as carbon dioxide or/and refrigerants. However, there is no common opinion if SC modeling fluids' correlations can be applied to SCW and vice versa. Thus, the objective of this work was to generalize SC carbon dioxide data with a new correlation, and also, to compare these data with SCW correlations The experimental data was analyzed, and a new correlation was developed as part of a larger project assessing the feasibility of Generation IV SCW reactor concepts. Results are given for supercritical heat-transfer for several combinations of wall and bulk-fluid temperatures that were below, at or above the pseudo critical temperature. Uncertainties of all primary parameters were estimated. Two modes of heat transfer at supercritical pressures have been identified: (I) Normal Heat Transfer (NHT), and (2) Deteriorated Heat Transfer (DHT) characterized by lower-than-expected HTCs (i.e., higher-than-expected wall temperatures) than in the normal heat-transfer regime. These heat-transfer data are

  1. Critical heat flux and flow pattern for water flow in annular geometry

    International Nuclear Information System (INIS)

    Park, Jae Wook; Baek, Won Pil; Chang, Soon Heung

    1996-01-01

    An experimental study on critical heat flux (CHF) and two-phase flow visualization has been performed for water flow in internally-heated, vertical, concentric annuli under near atmospheric pressure. Tests have been done under stable forced-circulation, upward and downward flow conditions with three test sections of relatively large gap widths (heated length = 0.6 m, inner diameter = 19 mm, outer diameter = 29, 35 and 51 mm). The outer wall of the test section was made up of the transparent Pyrex tube to allow the observation of flow patterns near the CHF occurrence. The CHF mechanism was changed in the order of flooding, churn-to-annular flow transition, and local dryout under a large bubble in churn flow as the flow rate was increased from zero to higher values. Observed parametric trends are consistent with the previous understanding except that the CHF for downward flow is considerably lower than that for upward flow

  2. An improved model to determine the inception of positive upward leader–streamer system considering the leader propagation during dark period

    International Nuclear Information System (INIS)

    Xie Shijun; He Junjia; Chen Weijiang

    2013-01-01

    Stem–leader transition and front-streamer inception are two essential conditions for the inception of positive upward leader–streamer system (LSS). Previous models have not considered the initial-leader propagation during dark period and have not been verified systematically. In this paper, a series of positive upward discharge simulation experiments was designed and carried out. Characteristic parameters of the discharge process related to the inception of positive upward LSS, namely, the first-corona inception voltage, the first-corona charge, the dark period, and the LSS inception voltage, were obtained. By comparing these experiment results with simulation results calculated using previous models, it was found that it is improper to assume that the length of the initial leader is a fixed value. Finally, an improved inception model of positive upward LSS considering the leader propagation during dark period was developed and verified with experiment results.

  3. Hydrodynamic delivery of plasmid DNA encoding human FcγR-Ig dimers blocks immune-complex mediated inflammation in mice.

    Science.gov (United States)

    Shashidharamurthy, R; Machiah, D; Bozeman, E N; Srivatsan, S; Patel, J; Cho, A; Jacob, J; Selvaraj, P

    2012-09-01

    Therapeutic use and function of recombinant molecules can be studied by the expression of foreign genes in mice. In this study, we have expressed human Fcγ receptor-Ig fusion molecules (FcγR-Igs) in mice by administering FcγR-Ig plasmid DNAs hydrodynamically and compared their effectiveness with purified molecules in blocking immune-complex (IC)-mediated inflammation in mice. The concentration of hydrodynamically expressed FcγR-Igs (CD16A(F)-Ig, CD32A(R)-Ig and CD32A(H)-Ig) reached a maximum of 130 μg ml(-1) of blood within 24 h after plasmid DNA administration. The in vivo half-life of FcγR-Igs was found to be 9-16 days and western blot analysis showed that the FcγR-Igs were expressed as a homodimer. The hydrodynamically expressed FcγR-Igs blocked 50-80% of IC-mediated inflammation up to 3 days in a reverse passive Arthus reaction model. Comparative analysis with purified molecules showed that hydrodynamically expressed FcγR-Igs are more efficient than purified molecules in blocking IC-mediated inflammation and had a higher half-life. In summary, these results suggest that the administration of a plasmid vector with the FcγR-Ig gene can be used to study the consequences of blocking IC binding to FcγRs during the development of inflammatory diseases. This approach may have potential therapeutic value in treating IC-mediated inflammatory autoimmune diseases such as lupus, arthritis and autoimmune vasculitis.

  4. Hematopoietic properties of granulocyte colony-stimulating factor/immunoglobulin (G-CSF/IgG-Fc fusion proteins in normal and neutropenic rodents.

    Directory of Open Access Journals (Sweden)

    George N Cox

    Full Text Available Previously we showed that granulocyte colony-stimulating factor (G-CSF in vitro bioactivity is preserved when the protein is joined via a flexible 7 amino acid linker to an immunoglobulin-1 (IgG1-Fc domain and that the G-CSF/IgG1-Fc fusion protein possessed a longer circulating half-life and improved hematopoietic properties compared to G-CSF in normal rats. We have extended this analysis by comparing the relative hematopoietic potencies of G-CSF/IgG1-Fc to G-CSF in normal mice and to G-CSF and polyethylene glycol (PEG -modified G-CSF in neutropenic rats. Mice were treated for 5 days using different doses and dosing regimens of G-CSF/IgG1-Fc or G-CSF and circulating neutrophil levels in the animals measured on Day 6. G-CSF/IgG1-Fc stimulated greater increases in blood neutrophils than comparable doses of G-CSF when administered using daily, every other day or every third day dosing regimens. In rats made neutropenic with cyclophosphamide, G-CSF/IgG1-Fc accelerated recovery of blood neutrophils to normal levels (from Day 9 to Day 5 when administered as 5 daily injections or as a single injection on Day 1. By contrast, G-CSF accelerated neutrophil recovery when administered as 5 daily injections, but not when administered as a single injection. G-CSF/IgG1-Fc was as effective as PEG-G-CSF at accelerating neutrophil recovery following a single injection in neutropenic rats. G-CSF/IgG1-Fc and G-CSF/IgG4-Fc fusion proteins in which the 7 amino acid linker was deleted also were effective at accelerating neutrophil recovery following a single injection in neutropenic rats. These studies confirm the enhanced in vivo hematopoietic properties of G-CSF/IgG-Fc fusion proteins.

  5. Physics of magnetic flux ropes

    Science.gov (United States)

    Russell, C. T.; Priest, E. R.; Lee, L. C.

    The present work encompasses papers on the structure, waves, and instabilities of magnetic flux ropes (MFRs), photospheric flux tubes (PFTs), the structure and heating of coronal loops, solar prominences, coronal mass ejections and magnetic clouds, flux ropes in planetary ionospheres, the magnetopause, magnetospheric field-aligned currents and flux tubes, and the magnetotail. Attention is given to the equilibrium of MFRs, resistive instability, magnetic reconnection and turbulence in current sheets, dynamical effects and energy transport in intense flux tubes, waves in solar PFTs, twisted flux ropes in the solar corona, an electrodynamical model of solar flares, filament cooling and condensation in a sheared magnetic field, the magnetopause, the generation of twisted MFRs during magnetic reconnection, ionospheric flux ropes above the South Pole, substorms and MFR structures, evidence for flux ropes in the earth magnetotail, and MFRs in 3D MHD simulations.

  6. Coupling Thermal and Chemical Signatures of Crustal Magma Bodies: Energy-Constrained Eruption, Recharge, Assimilation, and Fractional Crystallization (E'RAχFC)

    Science.gov (United States)

    Bohrson, W. A.; Spera, F. J.

    2004-12-01

    Energy-Constrained Eruption, Recharge, Assimilation and Fractional Crystallization (E'RAχFC) tracks the evolution of an open-system magmatic system by coupling conservation equations governing energy, mass and species (isotopes and trace elements). By linking the compositional characteristics of a composite magmatic system (host magma, recharge magma, wallrock, eruptive reservoir) to its mass and energy fluxes, predictions can be made about the chemical evolution of systems characterized by distinct compositional and thermal characteristics. An interesting application of E'RAχFC involves documenting the influence distinct thermal regimes have on the chemical evolution of magmatic systems. Heat transfer between a magma-country rock system at epizonal depths can be viewed as a conjugate heat transfer problem in which the average country rock-magma boundary temperature, Tb, is governed by the relative vigor of hydrothermal convection in the country rock vs. magma convection. For cases where hydrothermal circulation is vigorous and magmatic heat is efficiently transported away from the boundary, contact aureole temperatures (~Tb) are low. In cases where magmatic heat can not be efficiently transported away from the boundary and hydrothermal cells are absent or poorly developed, Tb is relatively high. Simultaneous solution of the differential equations governing momentum and energy conservation and continuity for the coupled hydrothermal-magmatic conjugate heat transfer system enables calculation of the characteristic timescale for EC-RAFC evolution and development of hydrothermal deposits as a function of material and medium properties, sizes of systems and relative efficiency of hydrothermal vs. magmatic heat transfer. Characteristic timescales lie in the range 102-106 yr depending on system size, magma properties and permeability among other parameters. In E'RAχFC, Tb is approximated by the user-defined equilibration temperature, Teq, which is the temperature at

  7. Near bed suspended sediment flux by single turbulent events

    Science.gov (United States)

    Amirshahi, Seyed Mohammad; Kwoll, Eva; Winter, Christian

    2018-01-01

    The role of small scale single turbulent events in the vertical mixing of near bed suspended sediments was explored in a shallow shelf sea environment. High frequency velocity and suspended sediment concentration (SSC; calibrated from the backscatter intensity) were collected using an Acoustic Doppler Velocimeter (ADV). Using quadrant analysis, the despiked velocity time series was divided into turbulent events and small background fluctuations. Reynolds stress and Turbulent Kinetic Energy (TKE) calculated from all velocity samples, were compared to the same turbulent statistics calculated only from velocity samples classified as turbulent events (Reevents and TKEevents). The comparison showed that Reevents and TKEevents was increased 3 and 1.6 times, respectively, when small background fluctuations were removed and that the correlation with SSC for TKE could be improved through removal of the latter. The correlation between instantaneous vertical turbulent flux (w ‧) and SSC fluctuations (SSC ‧) exhibits a tidal pattern with the maximum correlation at peak ebb and flood currents, when strong turbulent events appear. Individual turbulent events were characterized by type, strength, duration and length. Cumulative vertical turbulent sediment fluxes and average SSC associated with individual turbulent events were calculated. Over the tidal cycle, ejections and sweeps were the most dominant events, transporting 50% and 36% of the cumulative vertical turbulent event sediment flux, respectively. Although the contribution of outward interactions to the vertical turbulent event sediment flux was low (11%), single outward interaction events were capable of inducing similar SSC ‧ as sweep events. The results suggest that on time scales of tens of minutes to hours, TKE may be appropriate to quantify turbulence in sediment transport studies, but that event characteristics, particular the upward turbulent flux need to be accounted for when considering sediment transport

  8. Critical heat-flux experiments under low-flow conditions in a vertical annulus

    International Nuclear Information System (INIS)

    Mishima, K.; Ishii, M.

    1982-03-01

    An experimental study was performed on critical heat flux (CHF) at low flow conditions for low pressure steam-water upward flow in an annulus. The test section was transparent, therefore, visual observations of dryout as well as various instrumentations were made. The data indicated that a premature CHF occurred due to flow regime transition from churn-turbulent to annular flow. It is shown that the critical heat flux observed in the experiment is essentially similar to a flooding-limited burnout and the critical heat flux can be well reproduced by a nondimensional correlation derived from the previously obtained criterion for flow regime transition. The observed CHF values are much smaller than the standard high quality CHF criteria at low flow, corresponding to the annular flow film dryout. This result is very significant, because the coolability of a heater surface at low flow rates can be drastically reduced by the occurrence of this mode of CHF

  9. Viscous flux flow velocity and stress distribution in the Kim model of a long rectangular slab superconductor

    Science.gov (United States)

    Yang, Yong; Chai, Xueguang

    2018-05-01

    When a bulk superconductor endures the magnetization process, enormous mechanical stresses are imposed on the bulk, which often leads to cracking. In the present work, we aim to resolve the viscous flux flow velocity υ 0/w, i.e. υ 0 (because w is a constant) and the stress distribution in a long rectangular slab superconductor for the decreasing external magnetic field (B a ) after zero-field cooling (ZFC) and field cooling (FC) using the Kim model and viscous flux flow equation simultaneously. The viscous flux flow velocity υ 0/w and the magnetic field B* at which the body forces point away in all of the slab volumes during B a reduction, are determined by both B a and the decreasing rate (db a /dt) of the external magnetic field normalized by the full penetration field B p . In previous studies, υ 0/w obtained by the Bean model with viscous flux flow is only determined by db a /dt, and the field B* that is derived only from the Kim model is a positive constant when the maximum external magnetic field is chosen. This means that the findings in this paper have more physical contents than the previous results. The field B* stress changing with decreasing field B a after ZFC if B* ≤ 0. The effect of db a /dt on the stress is significant in the cases of both ZFC and FC.

  10. A dry-spot model for the prediction of critical heat flux in water boiling in bubbly flow regime

    International Nuclear Information System (INIS)

    Ha, Sang Jun; No, Hee Cheon

    1997-01-01

    This paper presents a prediction of critical heat flux (CHF) in bubbly flow regime using dry-spot model proposed recently by authors for pool and flow boiling CHF and existing correlations for forced convective heat transfer coefficient, active site density and bubble departure diameter in nucleate boiling region. Without any empirical constants always present in earlier models, comparisons of the model predictions with experimental data for upward flow of water in vertical, uniformly-heated round tubes are performed and show a good agreement. The parametric trends of CHF have been explored with respect to variation in pressure, tube diameter and length, mass flux and inlet subcooling

  11. A relaxed eddy accumulation system for measuring vertical fluxes of nitrous acid

    Directory of Open Access Journals (Sweden)

    X. Ren

    2011-10-01

    Full Text Available A relaxed eddy accumulation (REA system combined with a nitrous acid (HONO analyzer was developed to measure atmospheric HONO vertical fluxes. The system consists of three major components: (1 a fast-response sonic anemometer measuring both vertical wind velocity and air temperature, (2 a fast-response controlling unit separating air motions into updraft and downdraft samplers by the sign of vertical wind velocity, and (3 a highly sensitive HONO analyzer based on aqueous long path absorption photometry that measures HONO concentrations in the updrafts and downdrafts. A dynamic velocity threshold (±0.5σw, where σw is a standard deviation of the vertical wind velocity was used for valve switching determined by the running means and standard deviations of the vertical wind velocity. Using measured temperature as a tracer and the average values from two field deployments, the flux proportionality coefficient, β, was determined to be 0.42 ± 0.02, in good agreement with the theoretical estimation. The REA system was deployed in two ground-based field studies. In the California Research at the Nexus of Air Quality and Climate Change (CalNex study in Bakersfield, California in summer 2010, measured HONO fluxes appeared to be upward during the day and were close to zero at night. The upward HONO flux was highly correlated to the product of NO2 and solar radiation. During the Biosphere Effects on Aerosols and Photochemistry Experiment (BEARPEX 2009 at Blodgett Forest, California in July 2009, the overall HONO fluxes were small in magnitude and were close to zero. Causes for the different HONO fluxes in the two different environments are briefly discussed.

  12. Manufacturing process used to produce long-acting recombinant factor VIII Fc fusion protein.

    Science.gov (United States)

    McCue, Justin; Kshirsagar, Rashmi; Selvitelli, Keith; Lu, Qi; Zhang, Mingxuan; Mei, Baisong; Peters, Robert; Pierce, Glenn F; Dumont, Jennifer; Raso, Stephen; Reichert, Heidi

    2015-07-01

    Recombinant factor VIII Fc fusion protein (rFVIIIFc) is a long-acting coagulation factor approved for the treatment of hemophilia A. Here, the rFVIIIFc manufacturing process and results of studies evaluating product quality and the capacity of the process to remove potential impurities and viruses are described. This manufacturing process utilized readily transferable and scalable unit operations and employed multi-step purification and viral clearance processing, including a novel affinity chromatography adsorbent and a 15 nm pore size virus removal nanofilter. A cell line derived from human embryonic kidney (HEK) 293H cells was used to produce rFVIIIFc. Validation studies evaluated identity, purity, activity, and safety. Process-related impurity clearance and viral clearance spiking studies demonstrate robust and reproducible removal of impurities and viruses, with total viral clearance >8-15 log10 for four model viruses (xenotropic murine leukemia virus, mice minute virus, reovirus type 3, and suid herpes virus 1). Terminal galactose-α-1,3-galactose and N-glycolylneuraminic acid, two non-human glycans, were undetectable in rFVIIIFc. Biochemical and in vitro biological analyses confirmed the purity, activity, and consistency of rFVIIIFc. In conclusion, this manufacturing process produces a highly pure product free of viruses, impurities, and non-human glycan structures, with scale capabilities to ensure a consistent and adequate supply of rFVIIIFc. Copyright © 2015 Biogen. Published by Elsevier Ltd.. All rights reserved.

  13. FC LSEI WNNLS, Least-Square Fitting Algorithms Using B Splines

    International Nuclear Information System (INIS)

    Hanson, R.J.; Haskell, K.H.

    1989-01-01

    1 - Description of problem or function: FC allows a user to fit dis- crete data, in a weighted least-squares sense, using piece-wise polynomial functions represented by B-Splines on a given set of knots. In addition to the least-squares fitting of the data, equality, inequality, and periodic constraints at a discrete, user-specified set of points can be imposed on the fitted curve or its derivatives. The subprograms LSEI and WNNLS solve the linearly-constrained least-squares problem. LSEI solves the class of problem with general inequality constraints, and, if requested, obtains a covariance matrix of the solution parameters. WNNLS solves the class of problem with non-negativity constraints. It is anticipated that most users will find LSEI suitable for their needs; however, users with inequalities that are single bounds on variables may wish to use WNNLS. 2 - Method of solution: The discrete data are fit by a linear combination of piece-wise polynomial curves which leads to a linear least-squares system of algebraic equations. Additional information is expressed as a discrete set of linear inequality and equality constraints on the fitted curve which leads to a linearly-constrained least-squares system of algebraic equations. The solution of this system is the main computational problem solved

  14. Intracellular calcium mobilization in human lymphocytes in the presence of synthetic IgG Fc peptides

    International Nuclear Information System (INIS)

    Plummer, J.M.; Panahi, Y.P.; McClurg, M.R.; Hahn, G.S.; Naemura, J.R.

    1986-01-01

    Certain synthetic peptides derived from the Fc region of human IgG can suppress the mixed lymphocyte response. These peptides were tested for the ability to induce intracellular calcium mobilization in human lymphocytes using fura-2/calcium fluorescence. T cells were isolated by rosetting and were > 90% OKT3 positive. Lymphocytes were incubated with the acetoxymethyl ester of fura-2 (10 μM) for 60 minutes at 37 0 C. Fluorescence intensity changes at 505 nm were monitored at an excitation lambda of 340 nm. Fura-2 was not cytotoxic compared to quin-2 since fura-2 loaded mononuclear cells incorporated 3 H-thymidine when stimulated by PHA, succinyl Con A, PWM or LPS-STM whereas quin-2 loaded cells showed a dose dependent inhibition of proliferation. Those synthetic peptides (5 to 400 μg/ml) that suppressed the MLR induced a dose dependent increase in intracellular calcium in mononuclear cells, lymphocytes, non-T cells and T cells. The fura-2 calcium fluorescence time course response was similar for peptide, PHA and succinyl Con A. These results suggest that these immunoregulatory peptides suppress 3 H-thymidine incorporation at a point after intracellular calcium mobilization and that fura-2 has advantages over quin-2 in measuring intracellular calcium levels in lymphocytes

  15. Chlorotoxin Fused to IgG-Fc Inhibits Glioblastoma Cell Motility via Receptor-Mediated Endocytosis

    Directory of Open Access Journals (Sweden)

    Tomonari Kasai

    2012-01-01

    Full Text Available Chlorotoxin is a 36-amino acid peptide derived from Leiurus quinquestriatus (scorpion venom, which has been shown to inhibit low-conductance chloride channels in colonic epithelial cells. Chlorotoxin also binds to matrix metalloproteinase-2 and other proteins on glioma cell surfaces. Glioma cells are considered to require the activation of matrix metalloproteinase-2 during invasion and migration. In this study, for targeting glioma, we designed two types of recombinant chlorotoxin fused to human IgG-Fcs with/without a hinge region. Chlorotoxin fused to IgG-Fcs was designed as a dimer of 60 kDa with a hinge region and a monomer of 30 kDa without a hinge region. The monomeric and dimeric forms of chlorotoxin inhibited cell proliferation at 300 nM and induced internalization in human glioma A172 cells. The monomer had a greater inhibitory effect than the dimer; therefore, monomeric chlorotoxin fused to IgG-Fc was multivalently displayed on the surface of bionanocapsules to develop a drug delivery system that targeted matrix metalloproteinase-2. The target-dependent internalization of bionanocapsules in A172 cells was observed when chlorotoxin was displayed on the bionanocapsules. This study indicates that chlorotoxin fused to IgG-Fcs could be useful for the active targeting of glioblastoma cells.

  16. Autophagy mediates cytotoxicity of human colorectal cancer cells treated with garcinielliptone FC.

    Science.gov (United States)

    Won, Shen-Jeu; Yen, Cheng-Hsin; Lin, Ting-Yu; Jiang-Shieh, Ya-Fen; Lin, Chun-Nan; Chen, Jyun-Ti; Su, Chun-Li

    2018-01-01

    The tautomeric pair of garcinielliptone FC (GFC) is a novel tautomeric pair of polyprenyl benzophenonoid isolated from the pericarps of Garcinia subelliptica Merr. (G. subelliptica, Clusiaceae), a tree with abundant sources of polyphenols. Our previous report demonstrated that GFC induced apoptosis on various types of human cancer cell lines including chemoresistant human colorectal cancer HT-29 cells. In the present study, we observed that many autophagy-related genes in GFC-treated HT-29 cells were up- and down-regulated using a cDNA microarray containing oncogenes and kinase genes. GFC-induced autophagy of HT-29 cells was confirmed by observing the formation of acidic vesicular organelles, LC3 puncta, and double-membrane autophagic vesicles using flow cytometry, confocal microscopy, and transmission electron microscopy, respectively. Inhibition of AKT/mTOR/P70S6K signaling as well as formation of Atg5-Atg12 and PI3K/Beclin-1 complexes were observed using Western blot. Administration of autophagy inhibitor (3-methyladenine and shRNA Atg5) and apoptosis inhibitor Z-VAD showed that the GFC-induced autophagy was cytotoxic form and GFC-induced apoptosis enhanced GFC-induced autophagy. Our data suggest the involvement of autophagy and apoptosis in GFC-induced anticancer mechanisms of human colorectal cancer. © 2017 Wiley Periodicals, Inc.

  17. Heat flux variations over sea-ice observed at the coastal area of the Sejong Station, Antarctica

    Science.gov (United States)

    Park, S.; Choi, T.; Kim, S.

    2012-12-01

    This study presents variations of sensible heat flux and latent heat flux over sea-ice observed in 2011 from the 10-m flux tower located at the coast of the Sejong Station on King George Island, Antarctica. A period from June to November was divided into three parts: "Freezing", "Frozen", and "Melting" periods based on daily monitoring of sea state and hourly photos looking at the Marian Cove in front of the Sejong Station. The division of periods enabled us to look into the heat flux variations depending on the sea-ice conditions. Over freezing sea surface during the freezing period of late June, daily mean sensible heat flux was -11.9 Wm-2 and daily mean latent heat flux was +16.3 Wm-2. Over the frozen sea-ice, daily mean sensible heat flux was -10.4 Wm-2 while daily mean latent heat flux was +2.4 Wm-2. During the melting period of mid-October to early November, magnitudes of sensible heat flux increased to -14.2 Wm-2 and latent heat flux also increased to +13.5 Wm-2. In short, latent heat flux was usually upward over sea-ice most of the time while sensible heat flux was downward from atmosphere to sea-ice. Magnitudes of the fluxes were small but increased when freezing or melting of sea-ice was occurring. Especially, latent heat flux increased five to six times compared to that of "frozen" period implying that early melting of sea-ice may cause five to six times larger supply of moisture to the atmosphere.

  18. Australian methane fluxes

    International Nuclear Information System (INIS)

    Williams, D.J.

    1990-01-01

    Estimates are provided for the amount of methane emitted annually into the atmosphere in Australia for a variety of sources. The sources considered are coal mining, landfill, motor vehicles, natural gas suply system, rice paddies, bushfires, termites, wetland and animals. This assessment indicates that the major sources of methane are natural or agricultural in nature and therefore offer little scope for reduction. Nevertheless the remainder are not trival and reduction of these fluxes could play a significant part in any Australian action on the greenhouse problem. 19 refs., 7 tabs., 1 fig

  19. Turbulent fluxes of momentum and heat over land in the High-Arctic summer: the influence of observation techniques

    Directory of Open Access Journals (Sweden)

    Anna Sjöblom

    2014-06-01

    Full Text Available Different observation techniques for atmospheric turbulent fluxes of momentum and sensible heat were tested in a High-Arctic valley in Svalbard during two consecutive summers (June–August in 2010 and 2011. The gradient method (GM and the bulk method (BM have been compared to the more direct eddy covariance method (ECM in order to evaluate if relatively robust and cheap instrumentation with low power consumption can be used as a means to increase the number of observations, especially at remote locations where instruments need to be left unattended for extended periods. Such campaigns increase knowledge about the snow-free surface exchange processes, an area which is relatively little investigated compared to snow-covered ground. The GM agreed closely to the ECM, especially for momentum flux where the two methods agree within 5%. For sensible heat flux, the GM produces, on average, approximately 40% lower values for unstable stratification and 67% lower for stable stratification. However, this corresponds to only 20 and 12 W m−2, respectively. The BM, however, shows a greater scatter and larger differences for both parameters. In addition to testing these methods, radiation properties were measured and the surface albedo was found to increase through the summer, from approximately 0.1 to 0.2. The surface energy budget shows that the sensible heat flux is usually directed upwards for the whole summer, while the latent heat flux is upwards in June, but becomes downward in July and August.

  20. The Role of Bullfighting and FC Barcelona in the Emancipation of Catalonia from Spain (El papel de la corrida de toros y FC Barcelona en la emancipación de Cataluña de España

    Directory of Open Access Journals (Sweden)

    John A. TKac

    2015-06-01

    Full Text Available Abstract: This paper looks at the role that bullfighting and FC Barcelona have played in the growing independence movement in Catalonia. This article will discuss nations, the importance of bullfighting and soccer to Iberian cultures, Catalan political parties and their role in the nationalist movement, the vote to prohibit bullfighting and FC Barcelona´s increasing political conscious. I conclude that bullfighting and soccer have been used by political parties and those associated with the nationalist movement to foster feelings of difference with Spain. These feelings have been passed from the top down to the Catalan people and risk alienating those who are not in agreement with the nationalist movement.Resumen: Este trabajo examina el papel que la corrida de toros y el equipo de fútbol FC Barcelona han hecho en el movimiento continuo hacia la independencia en Cataluña. Discute el concepto de la nación, la importancia de las corridas y el fútbol en culturas ibéricas, partidos políticos catalanes y su rol en el voto a favor de la prohibición de las corridas en Cataluña y la evolución de la conciencia política cada vez más evidente de FC Barcelona. Concluyo que los partidos políticos y otros asociados con el movimiento hacia la independencia se han aprovechado de las corridas y el fútbol para destacar diferencias culturales con España. Esta actitud de diferencia se ha trasladado de arriba-abajo al pueblo catalán y el movimiento nacionalista corre el riesgo de alienar a los que no comparten sus creencias.