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Sample records for transient cytokine response

  1. Cytokine Response to Exercise and Its Modulation

    OpenAIRE

    Katsuhiko Suzuki

    2018-01-01

    Strenuous exercise induces such inflammatory responses as leukocytosis (neutrophilia) and symptoms as delayed-onset muscle soreness and swelling. However, the association between inflammatory mediator cytokines and oxidative stress is not fully delineated. Herein, in addition to basic background information on cytokines, research findings on exertional effects on cytokine release and the underlying mechanisms and triggers are introduced. Then, the associations among cytokine responses, oxidat...

  2. Cytokine Response to Exercise and Its Modulation

    Directory of Open Access Journals (Sweden)

    Katsuhiko Suzuki

    2018-01-01

    Full Text Available Strenuous exercise induces such inflammatory responses as leukocytosis (neutrophilia and symptoms as delayed-onset muscle soreness and swelling. However, the association between inflammatory mediator cytokines and oxidative stress is not fully delineated. Herein, in addition to basic background information on cytokines, research findings on exertional effects on cytokine release and the underlying mechanisms and triggers are introduced. Then, the associations among cytokine responses, oxidative stress, and tissue damage are described not only in overloaded skeletal muscle, but also in other internal organs. Furthermore, we introduce preventive countermeasures against the exhaustive exercise-induced pathogenesis together with the possibility of antioxidant interventions.

  3. Stationary and Transient Response Statistics

    DEFF Research Database (Denmark)

    Madsen, Peter Hauge; Krenk, Steen

    1982-01-01

    The covariance functions for the transient response of a linear MDOF-system due to stationary time limited excitation with an arbitrary frequency content are related directly to the covariance functions of the stationary response. For rational spectral density functions closed form expressions fo...

  4. Inactivated Parapoxvirus ovis induces a transient increase in the expression of proinflammatory, Th1-related, and autoregulatory cytokines in mice

    International Nuclear Information System (INIS)

    Anziliero, D.; Weiblen, R.; Kreutz, L.C.; Spilki, F.; Flores, E.F.

    2014-01-01

    The immunostimulatory properties of inactivated Parapoxvirus ovis (iPPVO) have long been investigated in different animal species and experimental settings. In this study, we investigated the effects of iPPVO on cytokine expression in mice after intraperitoneal inoculation. Spleen and sera collected from iPPVO-treated mice at intervals after inoculation were submitted to cytokine mRNA determination by real-time PCR (qPCR), serum protein concentration by ELISA, and interferon (IFN)-α/β activity by bioassay. The spleen of iPPVO-treated animals showed a significant increase in mRNA expression of all cytokines assayed, with different kinetics and magnitude. Proinflammatory cytokines interleukin (IL)-1β, tumor necrosis factor-alpha (TNF-α), and IL-8 mRNA peaked at 24 hours postinoculation (hpi; 5.4-fold increase) and 48 hpi (3- and 10-fold increases), respectively. A 15-fold increase in IFN-γ and 6-fold IL-12 mRNA increase were detected at 48 and 24 hpi, respectively. Increased expression of autoregulatory cytokines (Th2), mainly IL-10 and IL-4, could be detected at later times (72 and 96 hpi) with peaks of 4.7- and 4.9-fold increases, respectively. IFN-I antiviral activity against encephalomyocarditis virus was demonstrated in sera of treated animals between 6 and 12 hpi, with a >90% reduction in the number of plaques. Measurement of serum proteins by ELISA revealed increased levels of IL-1, TNF-α, IL-12, IFN-γ, and IL-10, with kinetics similar to those observed by qPCR, especially for IL-12 and IFN-γ. These data demonstrate that iPPVO induced a transient and complex cytokine response, initially represented by Th1-related cytokines followed by autoregulatory and Th2 cytokines

  5. Inactivated Parapoxvirus ovis induces a transient increase in the expression of proinflammatory, Th1-related, and autoregulatory cytokines in mice

    Energy Technology Data Exchange (ETDEWEB)

    Anziliero, D.; Weiblen, R. [Setor de Virologia, Departamento de Medicina Veterinária Preventiva, Universidade Federal de Santa Maria, Santa Maria, RS, Brasil, Setor de Virologia, Departamento de Medicina Veterinária Preventiva, Universidade Federal de Santa Maria, Santa Maria, RS (Brazil); Kreutz, L.C. [Programa de Pós-Graduação em Bioexperimentação, Faculdade de Agronomia e Medicina Veterinária, Universidade de Passo Fundo, Passo Fundo, RS, Brasil, Programa de Pós-Graduação em Bioexperimentação, Faculdade de Agronomia e Medicina Veterinária, Universidade de Passo Fundo, Passo Fundo, RS (Brazil); Spilki, F. [Laboratório de Microbiologia Molecular, Instituto de Ciências da Saúde, Universidade Feevale, Novo Hamburgo, RS, Brasil, Laboratório de Microbiologia Molecular, Instituto de Ciências da Saúde, Universidade Feevale, Novo Hamburgo, RS (Brazil); Flores, E.F. [Setor de Virologia, Departamento de Medicina Veterinária Preventiva, Universidade Federal de Santa Maria, Santa Maria, RS, Brasil, Setor de Virologia, Departamento de Medicina Veterinária Preventiva, Universidade Federal de Santa Maria, Santa Maria, RS (Brazil)

    2014-02-17

    The immunostimulatory properties of inactivated Parapoxvirus ovis (iPPVO) have long been investigated in different animal species and experimental settings. In this study, we investigated the effects of iPPVO on cytokine expression in mice after intraperitoneal inoculation. Spleen and sera collected from iPPVO-treated mice at intervals after inoculation were submitted to cytokine mRNA determination by real-time PCR (qPCR), serum protein concentration by ELISA, and interferon (IFN)-α/β activity by bioassay. The spleen of iPPVO-treated animals showed a significant increase in mRNA expression of all cytokines assayed, with different kinetics and magnitude. Proinflammatory cytokines interleukin (IL)-1β, tumor necrosis factor-alpha (TNF-α), and IL-8 mRNA peaked at 24 hours postinoculation (hpi; 5.4-fold increase) and 48 hpi (3- and 10-fold increases), respectively. A 15-fold increase in IFN-γ and 6-fold IL-12 mRNA increase were detected at 48 and 24 hpi, respectively. Increased expression of autoregulatory cytokines (Th2), mainly IL-10 and IL-4, could be detected at later times (72 and 96 hpi) with peaks of 4.7- and 4.9-fold increases, respectively. IFN-I antiviral activity against encephalomyocarditis virus was demonstrated in sera of treated animals between 6 and 12 hpi, with a >90% reduction in the number of plaques. Measurement of serum proteins by ELISA revealed increased levels of IL-1, TNF-α, IL-12, IFN-γ, and IL-10, with kinetics similar to those observed by qPCR, especially for IL-12 and IFN-γ. These data demonstrate that iPPVO induced a transient and complex cytokine response, initially represented by Th1-related cytokines followed by autoregulatory and Th2 cytokines.

  6. Instrument response during overpower transients at TREAT

    International Nuclear Information System (INIS)

    Meek, C.C.; Bauer, T.H.; Hill, D.J.; Froehle, P.H.; Klickman, A.E.; Tylka, J.P.; Doerner, R.C.; Wright, A.E.

    1982-01-01

    A program to empirically analyze data residuals or noise to determine instrument response that occurs during in-pile transient tests is out-lined. As an example, thermocouple response in the Mark III loop during a severe overpower transient in TREAT is studied both in frequency space and in real-time. Time intervals studied included both constant power and burst portions of the power transient. Thermocouple time constants were computed. Benefits and limitations of the method are discussed

  7. Temperature transient response measurement in flowing water

    International Nuclear Information System (INIS)

    Rainbird, J.C.

    1980-01-01

    A specially developed procedure is described for determining the thermal transient response of thermocouples and other temperature transducers when totally immersed in flowing water. The high velocity heat transfer conditions associated with this facility enable thermocouple response times to be predicted in other fluids. These predictions can be confirmed by electrical analogue experiments. (author)

  8. Cytokine response to Escherichia coli in gnotobiotic pigs

    Czech Academy of Sciences Publication Activity Database

    Šplíchal, Igor; Šplíchalová, Alla; Trebichavský, Ilja

    2008-01-01

    Roč. 53, č. 2 (2008), s. 161-164 ISSN 0015-5632 R&D Projects: GA ČR GA523/05/0249 Institutional research plan: CEZ:AV0Z50200510 Keywords : germ-free pigs * escherichia coli * cytokine response Subject RIV: EE - Microbiology, Virology Impact factor: 1.172, year: 2008

  9. Modelling structural systems for transient response analysis

    International Nuclear Information System (INIS)

    Melosh, R.J.

    1975-01-01

    This paper introduces and reports success of a direct means of determining the time periods in which a structural system behaves as a linear system. Numerical results are based on post fracture transient analyses of simplified nuclear piping systems. Knowledge of the linear response ranges will lead to improved analysis-test correlation and more efficient analyses. It permits direct use of data from physical tests in analysis and simplication of the analytical model and interpretation of its behavior. The paper presents a procedure for deducing linearity based on transient responses. Given the forcing functions and responses of discrete points of the system at various times, the process produces evidence of linearity and quantifies an adequate set of equations of motion. Results of use of the process with linear and nonlinear analyses of piping systems with damping illustrate its success. Results cover the application to data from mathematical system responses. The process is successfull with mathematical models. In loading ranges in which all modes are excited, eight digit accuracy of predictions are obtained from the equations of motion deduced. Small changes (less than 0.01%) in the norm of the transfer matrices are produced by manipulation errors for linear systems yielding evidence that nonlinearity is easily distinguished. Significant changes (greater than five %) are coincident with relatively large norms of the equilibrium correction vector in nonlinear analyses. The paper shows that deducing linearity and, when admissible, quantifying linear equations of motion from transient response data for piping systems can be achieved with accuracy comparable to that of response data

  10. Growth hormone preferentially induces the rapid, transient expression of SOCS-3, a novel inhibitor of cytokine receptor signaling

    DEFF Research Database (Denmark)

    Adams, T E; Hansen, J A; Starr, R

    1998-01-01

    Four members (SOCS-1, SOCS-2, SOCS-3, and CIS) of a family of cytokine-inducible, negative regulators of cytokine receptor signaling have recently been identified. To address whether any of these genes are induced in response to growth hormone (GH), serum-starved 3T3-F442A fibroblasts were incuba...

  11. Oral warfarin intake affects skin inflammatory cytokine responses in rats.

    Science.gov (United States)

    Aleksandrov, Aleksandra Popov; Mirkov, Ivana; Zolotarevski, Lidija; Ninkov, Marina; Mileusnic, Dina; Kataranovski, Dragan; Kataranovski, Milena

    2017-09-01

    Warfarin is an anticoagulant used in prevention/prophylaxis of thromboembolism. Besides the effects on coagulation, non-hemorrhagic reactions have also been documented. Although cutaneous reactions were reported in some patients, the impact on skin immunity was not explored. In the present paper, the effect of 30-day oral warfarin intake on skin cytokine responses in rats was analyzed. Increased release of inflammatory cytokines (TNF, IL-1β and IL-10) was noted by skin explants from rats which received warfarin, but without effect on IL-6. No impact on epidermal cell cytokine secretion was seen, except a tendency of an increase of IL-6 response to stimulation with microbial product lipopolysaccharide (LPS). Topical application of contact allergen dinitrochlorobenzene (DNCB) resulted in slight (numerical solely) increase of TNF release by skin explants of warfarin-treated animals, while epidermal cells responded by increased secretion of all four cytokines examined. The data presented provide new information on the potential of oral warfarin to modulate skin innate immune activity. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Trichuris suis ova therapy for allergic rhinitis does not affect allergen-specific cytokine responses despite a parasite-specific cytokine response

    DEFF Research Database (Denmark)

    Bourke, C.D.; Mutapi, F.; Nausch, N.

    2012-01-01

    Parasitic helminths have been shown to reduce inflammation in most experimental models of allergic disease, and this effect is mediated via cytokine responses. However, in humans, the effects of controlled helminth infection on cytokine responses during allergy have not been studied....

  13. Cytokines and the Inception of CD8 T Cell Responses

    Science.gov (United States)

    Cox, Maureen A.; Harrington, Laurie E.; Zajac, Allan J.

    2011-01-01

    The activation and differentiation of CD8 T cells is a necessary first step that endows these cells with the phenotypic and functional properties required for the control of intracellular pathogens. The induction of the CD8 T cell responses typically results in the development of a massive overall population of effector cells, comprised of both highly functional but short-lived terminally differentiated cells, as well as a smaller subset of precursors that are predisposed to survive and transition into the memory T cell pool. In this article we discuss how inflammatory cytokines and IL-2 bias the initial response towards short-lived effector generation and also highlight the potential counterbalancing role of IL-21. PMID:21371940

  14. Stratum corneum cytokines and skin irritation response to sodium lauryl sulfate

    NARCIS (Netherlands)

    de Jongh, Cindy M.; Verberk, Maarten M.; Withagen, Carien E. T.; Jacobs, John J. L.; Rustemeyer, Thomas; Kezic, Sanja

    2006-01-01

    Little is known about cytokines involved in chronic irritant contact dermatitis. Individual cytokine profiles might explain at least part of the differences in the individual response to irritation. Our objective was to investigate the relation between baseline stratum corneum (SC) cytokine levels

  15. Transient response in granular bounded heap flows

    Science.gov (United States)

    Xiao, Hongyi; Ottino, Julio M.; Lueptow, Richard M.; Umbanhowar, Paul B.

    2017-11-01

    Heap formation, a canonical granular flow, is common in industry and is also found in nature. Here, we study the transition between steady flow states in quasi-2D bounded heaps by suddenly changing the feed rate from one fixed value to another. During the transition, in both experiments and discrete element method simulations, an additional wedge of flowing particles propagates over the rising free surface. The downstream edge of the wedge - the wedge front - moves downstream with velocity inversely proportional to the square root of time. An additional longer duration transient process continues after the wedge front reaches the downstream wall. The transient flux profile during the entire transition is well modeled by a diffusion-like equation derived from local mass balance and a local linear relation between the flux and the surface slope. Scalings for the transient kinematics during the flow transitions are developed based on the flux profiles. Funded by NSF Grant CBET-1511450.

  16. Photoperiodic Regulation of Behavioral Responsiveness to Proinflammatory Cytokines

    OpenAIRE

    Wen, Jarvi C.; Prendergast, Brian J.

    2007-01-01

    Symptoms of bacterial infection include decreases in body mass (cachexia), induction of depressive-like hedonic tone (anhedonia), decreases in food intake (anorexia), and increases in body temperature (fever). Recognition of bacteria by the innate immune system triggers the release of proinflammatory cytokines which induce these sickness behaviors via central and peripheral substrates. In Siberian hamsters, exposure to short day lengths decreases both the production of proinflammatory cytokin...

  17. Response of hyporheic zones to transient forcing

    Science.gov (United States)

    Singh, T.; Wu, L.; Gomez-Velez, J. D.; Krause, S.; Hannah, D. M.; Lewandowski, J.; Nuetzmann, G.

    2017-12-01

    Exchange of water, solutes, and energy between river channels and hyporheic zones (HZs) modulates biogeochemical cycling, regulates stream temperature and impacts ecological structure and function. Numerical modelling of HZ processes is required as field observations are challenging for transient flow. To gain a deeper mechanistic understanding of the effects of transient discharge on hyporheic exchange, we performed a systematic analysis using numerical experiments. In this case, we vary (i) the characteristics of time-varying flood events; (ii) river bedform geometry; (iii) river hydraulic geometry; and (iv) the magnitude and direction of groundwater fluxes (neutral, gaining and losing conditions). We conceptualize the stream bed as a two-dimensional system. Whereby the flow is driven by a dynamically changing head distribution at the water-sediment interface and is modulated by steady groundwater flow. Our model estimates both net values for a single bedform and spatial distributions of (i) the flow field; (ii) mean residence times; and (iii) the concentration of a conservative tracer. A detailed sensitivity analysis was performed by changing channel slope, flood characteristics, groundwater upwelling/downwelling fluxes and biogeochemical time-scales in different bedforms such as ripples, dunes and alternating bars. Results show that change of parameters can have a substantial impact on exchange fluxes which can lead to the expansion, contraction, emergence and/or dissipation of HZs . Our results also reveal that groundwater fluxes have different impacts on HZs during flood events, depending on the channel slope and bedform topography. It is found that topographies with smaller aspect ratios and shallower slopes are more affected by groundwater upwelling/downwelling fluxes during flood events. The analysis of biogeochemical transformations shows that discharge events can potentially affects the efficiencies of nitrate removal. Taking into consideration multiple

  18. Mycobacteria-specific cytokine responses as correlates of treatment response in active and latent tuberculosis.

    Science.gov (United States)

    Clifford, Vanessa; Tebruegge, Marc; Zufferey, Christel; Germano, Susie; Forbes, Ben; Cosentino, Lucy; McBryde, Emma; Eisen, Damon; Robins-Browne, Roy; Street, Alan; Denholm, Justin; Curtis, Nigel

    2017-08-01

    A biomarker indicating successful tuberculosis (TB) therapy would assist in determining appropriate length of treatment. This study aimed to determine changes in mycobacteria-specific antigen-induced cytokine biomarkers in patients receiving therapy for latent or active TB, to identify biomarkers potentially correlating with treatment success. A total of 33 adults with active TB and 36 with latent TB were followed longitudinally over therapy. Whole blood stimulation assays using mycobacteria-specific antigens (CFP-10, ESAT-6, PPD) were done on samples obtained at 0, 1, 3, 6 and 9 months. Cytokine responses (IFN-γ, IL-1ra, IL-2, IL-10, IL-13, IP-10, MIP-1β, and TNF-α) in supernatants were measured by Luminex xMAP immunoassay. In active TB cases, median IL-1ra (with CFP-10 and with PPD stimulation), IP-10 (CFP-10, ESAT-6), MIP-1β (ESAT-6, PPD), and TNF-α (ESAT-6) responses declined significantly over the course of therapy. In latent TB cases, median IL-1ra (CFP-10, ESAT-6, PPD), IL-2 (CFP-10, ESAT-6), and IP-10 (CFP-10, ESAT-6) responses declined significantly. Mycobacteria-specific cytokine responses change significantly over the course of therapy, and their kinetics in active TB differ from those observed in latent TB. In particular, mycobacteria-specific IL-1ra responses are potential correlates of successful therapy in both active and latent TB. Copyright © 2017 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

  19. Response of steam-water mixtures to pressure transients

    International Nuclear Information System (INIS)

    Hull, L.M.

    1985-01-01

    During the transition phase of a hypothetical core-disruptive accident in a liquid-metal fast breeder reactor, melting fuel-steel mixtures may begin to boil, resulting in a two-phase mixture of molten reactor fuel and steel vapor. Dispersal of this mixture by pressure transients may prevent recriticality of the fuel material. This paper describes the results of a series of experiments that investigated the response of two-phase mixtures to pressure transients. Simulant fluids (steam/water) were used in a transparent 10.2-cm-dia, 63.5-cm-long acrylic tube. The pressure transient was provided by releasing pressurized nitrogen from a supply tank. The data obtained are in the form of pressure-time records and high-speed movies. The varied parameters are initial void fraction (10% and 40%) and transient pressure magnitude (3.45 and 310 kPa)

  20. Modeling of Transient Response of the Wickless Heat Pipes

    International Nuclear Information System (INIS)

    Hussien, A.K.A.

    2013-01-01

    Thermosyphons transient response for startup from ambient temperature to steady state until shutdown conditions, is considered a stringent necessity for applications such as electronic, solar, geothermal and even nuclear reactors safety systems. This typically returns to the need to keep the temperature within certain limits before reaching critical conditions. A simple network model is derived for describing the transient response of closed two-phase thermosyphon (CTPT) at startup and shutdown states. In addition, for predicting the effect of operational characteristics of water/copper closed two-phase thermosyphon such as thermal load, filling ratio, evaporator length, and thermosyphon tube diameter. The thermosyphons operation was considered a thermal network of various components with different thermal resistances and dynamic responses. The network model consists of six sub-models. These models are pure conduction in walls of evaporator, adiabatic and condenser, and convection in evaporator pool, evaporator film, and condenser film. So, an energy balance for each sub-model was done to estimate temperatures, heat transfer coefficients, thermal resistances, time constant, and other thermal characteristics that describe the required transient response of the closed two-phase thermosyphon. Governing equations of the transient thermosyphon behavior can be simplified into a set of first-order linear ordinary differential equations. The Runge-Kutta method can be used to obtain transient thermosyphon temperatures from these equations.

  1. PORCINE CYTOKINE RESPONSES TO PAMP-STRUCTURES IN VITRO

    DEFF Research Database (Denmark)

    Sørensen, Nanna Skall; Skovgaard, Kerstin; Vorsholt, Henriette

    Pathogen-associated molecular patterns (PAMPs) are conserved microbial structures recognized by pattern-recognition receptors (PRRs) of the innate immune system. Binding of PAMPs by certain PRRs on dendritic cells induces these to express costimulatory molecules and cytokines, enabling an inducti...

  2. Noninvasive optical monitoring multiple physiological parameters response to cytokine storm

    Science.gov (United States)

    Li, Zebin; Li, Ting

    2018-02-01

    Cancer and other disease originated by immune or genetic problems have become a main cause of death. Gene/cell therapy is a highlighted potential method for the treatment of these diseases. However, during the treatment, it always causes cytokine storm, which probably trigger acute respiratory distress syndrome and multiple organ failure. Here we developed a point-of-care device for noninvasive monitoring cytokine storm induced multiple physiological parameters simultaneously. Oxy-hemoglobin, deoxy-hemoglobin, water concentration and deep-tissue/tumor temperature variations were simultaneously measured by extended near infrared spectroscopy. Detection algorithms of symptoms such as shock, edema, deep-tissue fever and tissue fibrosis were developed and included. Based on these measurements, modeling of patient tolerance and cytokine storm intensity were carried out. This custom device was tested on patients experiencing cytokine storm in intensive care unit. The preliminary data indicated the potential of our device in popular and milestone gene/cell therapy, especially, chimeric antigen receptor T-cell immunotherapy (CAR-T).

  3. Aspergillus fumigatus conidial melanin modulates host cytokine response.

    NARCIS (Netherlands)

    Chai, L.; Netea, M.G.; Sugui, J.; Vonk, A.G.; Sande, W.W. van de; Warris, A.; Kwon-Chung, K.J.; Kullberg, B.J.

    2010-01-01

    Melanin biopigments have been linked to fungal virulence. Aspergillus fumigatus conidia are melanised and are weakly immunogenic. We show that melanin pigments on the surface of resting Aspergillus fumigatus conidia may serve to mask pathogen-associated molecular patterns (PAMPs)-induced cytokine

  4. Cytokine responses in acute and persistent human parvovirus B19 infection

    DEFF Research Database (Denmark)

    Isa, A; Lundqvist, A; Lindblom, A

    2007-01-01

    The aim of this study was to characterize the proinflammatory and T helper (Th)1/Th2 cytokine responses during acute parvovirus B19 (B19) infection and determine whether an imbalance of the Th1/Th2 cytokine pattern is related to persistent B19 infection. Cytokines were quantified by multiplex beads...... immunoassay in serum from B19-infected patients and controls. The cytokine responses were correlated with B19 serology, quantitative B19 DNA levels and clinical symptoms. In addition to a proinflammatory response, elevated levels of the Th1 type of cytokines interleukin (IL)-2, IL-12 and IL-15 were evident...... at time of the initial peak of B19 viral load in a few patients during acute infection. This pattern was seen in the absence of an interferon (IFN)-gamma response. During follow-up (20-130 weeks post-acute infection) some of these patients had a sustained Th1 cytokine response. The Th1 cytokine response...

  5. Regulation of Cytokine Production by the Unfolded Protein Response; Implications for Infection and Autoimmunity

    OpenAIRE

    Judith A. Smith; Judith A. Smith

    2018-01-01

    Protein folding in the endoplasmic reticulum (ER) is an essential cell function. To safeguard this process in the face of environmental threats and internal stressors, cells mount an evolutionarily conserved response known as the unfolded protein response (UPR). Invading pathogens induce cellular stress that impacts protein folding, thus the UPR is well situated to sense danger and contribute to immune responses. Cytokines (inflammatory cytokines and interferons) critically mediate host defen...

  6. Response of dairy cattle to transient voltages and magnetic fields

    International Nuclear Information System (INIS)

    Reinemann, D.J.; Laughlin, N.K.; Stetson, L.E.

    1995-01-01

    Stray voltages in dairy facilities have been studied since the 1970's. Previous research using steady-state ac and dc voltages has defined cow-contact voltage levels which may cause behavior and associated production problems. This research was designed to address concerns over possible effects of transient voltages and magnetic fields on dairy cows. Dairy cows response to transient voltages and magnetic fields was measured. The waveforms of the transient voltages applied were: 5 cycles of 60-Hz ac with a total pulse time of 83 ms, 1 cycle of 60-Hz ac with a total pulse time of 16 ms, and 1 cycle of an ac square wave (spiking positive and negative) of 2-ms duration. Alternating magnetic fields were produced by passing 60-Hz ac fundamental frequency with 2nd and 3rd harmonic and random noise components in metal structures around the cows. The maximum magnetic field associated with this current flow was in excess of 4 G. A wide range of sensitivity to transient voltages was observed among cows. Response levels from 24 cows to each transient exposure were normally distributed. No responses to magnetic fields were observed

  7. Calculation of Lightning Transient Responses on Wind Turbine Towers

    Directory of Open Access Journals (Sweden)

    Xiaoqing Zhang

    2013-01-01

    Full Text Available An efficient method is proposed in this paper for calculating lightning transient responses on wind turbine towers. In the proposed method, the actual tower body is simplified as a multiconductor grid in the shape of cylinder. A set of formulas are given for evaluating the circuit parameters of the branches in the multiconductor grid. On the basis of the circuit parameters, the multiconductor grid is further converted into an equivalent circuit. The circuit equation is built in frequency-domain to take into account the effect of the frequency-dependent characteristic of the resistances and inductances on lightning transients. The lightning transient responses can be obtained by using the discrete Fourier transform with exponential sampling to take the inverse transform of the frequency-domain solution of the circuit equation. A numerical example has been given for examining the applicability of the proposed method.

  8. Academic stress-induced changes in Th1- and Th2-cytokine response

    Directory of Open Access Journals (Sweden)

    Areej M. Assaf

    2017-12-01

    Full Text Available Psychological stress stimulates physiological responses releasing catecholamines and corticoids, which act via corresponding receptors on immune cells, producing a shift in the cytokine balance. These responses are variable depending on the nature of stressors. The effect of the academic stress on the production of the Th1-cytokines (TNF-α, IFN-γ, IL-1β, IL-2, IL-6 and IL-8 and Th2-cytokines (IL-1ra, IL-4, IL-5 and IL-10 on 35 medical/health sciences students after completing their questionnaires was investigated. Blood samples were taken at three stages; baseline stage at the beginning, midterm and final academic examination stages. Plasma cortisol and cytokines were measured during the three stages. The last two stages were compared with the baseline non-stress period. Results of the stress induced during the final examination stage were the highest with a significant increase in cortisol release, IL-4, IL-5 and IL-1ra release with a shift in Th1:Th2 cytokines balance towards Th2. Whereby, the midterm stage did not show significant reduction in Th1-cytokines except for TNF-α, with an increase in IFN-γ level that was reduced in the third stage. Th2 cytokine, IL-1ra, had positive correlations with Th1 cytokines; IL-2 and IFN-γ in the second stage and IL-6 cytokine in the third stage. Cortisol was positively correlated with IL-8 in the last stage and heart rates had negative correlation with IL-10 in the first and last stages. Findings of this study indicate that exam stress down-regulates Th1 with a selective up-regulation of Th2-cytokines. In conclusion, Cortisol might have a role in suppressing the release of Th1- mediated cellular immune response which could increase the vulnerability among the students to infectious diseases.

  9. Academic stress-induced changes in Th1- and Th2-cytokine response.

    Science.gov (United States)

    Assaf, Areej M; Al-Abbassi, Reem; Al-Binni, Maysaa

    2017-12-01

    Psychological stress stimulates physiological responses releasing catecholamines and corticoids, which act via corresponding receptors on immune cells, producing a shift in the cytokine balance. These responses are variable depending on the nature of stressors. The effect of the academic stress on the production of the Th1-cytokines (TNF-α, IFN-γ, IL-1β, IL-2, IL-6 and IL-8) and Th2-cytokines (IL-1ra, IL-4, IL-5 and IL-10) on 35 medical/health sciences students after completing their questionnaires was investigated. Blood samples were taken at three stages; baseline stage at the beginning, midterm and final academic examination stages. Plasma cortisol and cytokines were measured during the three stages. The last two stages were compared with the baseline non-stress period. Results of the stress induced during the final examination stage were the highest with a significant increase in cortisol release, IL-4, IL-5 and IL-1ra release with a shift in Th1:Th2 cytokines balance towards Th2. Whereby, the midterm stage did not show significant reduction in Th1-cytokines except for TNF-α, with an increase in IFN-γ level that was reduced in the third stage. Th2 cytokine, IL-1ra, had positive correlations with Th1 cytokines; IL-2 and IFN-γ in the second stage and IL-6 cytokine in the third stage. Cortisol was positively correlated with IL-8 in the last stage and heart rates had negative correlation with IL-10 in the first and last stages. Findings of this study indicate that exam stress down-regulates Th1 with a selective up-regulation of Th2-cytokines. In conclusion, Cortisol might have a role in suppressing the release of Th1- mediated cellular immune response which could increase the vulnerability among the students to infectious diseases.

  10. Analysis of piping response to thermal and operational transients

    International Nuclear Information System (INIS)

    Wang, C.Y.

    1987-01-01

    The reactor piping system is an extremely complex three-dimensional structure. Maintaining its structural integrity is essential to the safe operation of the reactor and the steam-supply system. In the safety analysis, various transient loads can be imposed on the piping which may cause plastic deformation and possible damage to the system, including those generated from hydrodynamic wave propagations, thermal and operational transients, as well as the seismic events. At Argonne National Laboratory (ANL), a three-dimensional (3-D) piping code, SHAPS, aimed for short-duration transients due to wave propagation, has been developed. Since 1984, the development work has been shifted to the long-duration accidents originating from the thermal and operational transient. As a result, a new version of the code, SHAPS-2, is being established. This paper describes many features related to this later development. To analyze piping response generated from thermal and operational transients, a 3-D implicit finite element algorithm has been developed for calculating the hoop, flexural, axial, and torsional deformations induced by the thermomechanical loads. The analysis appropriately accounts for stresses arising from the temperature dependence of the elastic material properties, the thermal expansion of the materials, and the changes in the temperature-dependent yield surface. Thermal softening, failure, strain rate, creep, and stress ratching can also be considered

  11. Reducing Conservatism of Analytic Transient Response Bounds via Shaping Filters

    Science.gov (United States)

    Kwan, Aiyueh; Bedrossian, Nazareth; Jan, Jiann-Woei; Grigoriadis, Karolos; Hua, Tuyen (Technical Monitor)

    1999-01-01

    Recent results show that the peak transient response of a linear system to bounded energy inputs can be computed using the energy-to-peak gain of the system. However, analytically computed peak response bound can be conservative for a class of class bounded energy signals, specifically pulse trains generated from jet firings encountered in space vehicles. In this paper, shaping filters are proposed as a Methodology to reduce the conservatism of peak response analytic bounds. This Methodology was applied to a realistic Space Station assembly operation subject to jet firings. The results indicate that shaping filters indeed reduce the predicted peak response bounds.

  12. Atmospheric CO2 and climate: Importance of the transient response

    International Nuclear Information System (INIS)

    Schneider, S.H.; Thompson, S.L.

    1981-01-01

    Preliminary studies suggest that the thermal inertia of the upper layers of the oceans, combined with vertical mixing of deeper oceanic waters, could delay the response of the globally averaged surface temperature to an increasing atmospheric CO 2 concentration by a decade or so relative to equilibrium calculations. This study extends the global analysis of the transient response to zonal averages, using a hierarchy of simple energy balance models and vertical mixing assumptions for water exchange between upper and deeper oceanic layers. It is found that because of the latitudinal dependence of both thermal inertia and radiative and dynamic energy exchange mechanisms, the approach toward equilibrium of the surface temperature of various regions of the earth will be significantly different from the global average approach. This suggests that the actual time evolution of the horizontal surface temperature gradients--and any associated regional climatic anomalies-may well be significantly different from that suggested by equilibrium climatic modeling simulations (or those computed with a highly unrealistic geographic distribution of ocean thermal capacity). Also, the transient response as a function of latitude is significantly different between globally equivalent CO 2 and solar constant focusing runs. It is suggested that the nature of the transient response is a major uncertainty in characterizing the CO 2 problem and that study of this topic should become a major priority for future research. An appendix puts this issue in the context of the overall CO 2 problem

  13. Lithium Battery Transient Response as a Diagnostic Tool

    Science.gov (United States)

    Denisov, E.; Nigmatullin, R.; Evdokimov, Y.; Timergalina, G.

    2018-05-01

    Lithium batteries are currently used as the main energy storage for electronic devices. Progress in the field of portable electronic devices is significantly determined by the improvement of their weight/dimensional characteristics and specific capacity. In addition to the high reliability required of lithium batteries, in some critical applications proper diagnostics are required. Corresponding techniques allow prediction and prevention of operation interruption and avoidance of expensive battery replacement, and also provide additional benefits. Many effective diagnostic methods have been suggested; however, most of them require expensive experimental equipment, as well as interruption or strong perturbation of the operating mode. In the framework of this investigation, a simple diagnostic method based on analysis of transient processes is proposed. The transient response is considered as a reaction to an applied load variation that typically corresponds to normal operating conditions for most real applications. The transient response contains the same information as the impedance characteristic for the system operating in linear mode. Taking into account the large number of publications describing the impedance response associated with diagnostic methods, it can be assumed that the transient response contains a sufficient amount of information for creation of effective diagnostic systems. The proposed experimental installation is based on a controlled load, providing current variation, measuring equipment, and data processing electronics. It is proposed to use the second exponent parameters U 2 and β to estimate the state of charge for secondary lithium batteries. The proposed method improves the accuracy and reliability of a set of quantitative parameters associated with electrochemical energy sources.

  14. Transient Response Analysis of Metropolis Learning in Games

    KAUST Repository

    Jaleel, Hassan

    2017-10-19

    The objective of this work is to provide a qualitative description of the transient properties of stochastic learning dynamics like adaptive play, log-linear learning, and Metropolis learning. The solution concept used in these learning dynamics for potential games is that of stochastic stability, which is based on the stationary distribution of the reversible Markov chain representing the learning process. However, time to converge to a stochastically stable state is exponential in the inverse of noise, which limits the use of stochastic stability as an effective solution concept for these dynamics. We propose a complete solution concept that qualitatively describes the state of the system at all times. The proposed concept is prevalent in control systems literature where a solution to a linear or a non-linear system has two parts, transient response and steady state response. Stochastic stability provides the steady state response of stochastic learning rules. In this work, we study its transient properties. Starting from an initial condition, we identify the subsets of the state space called cycles that have small hitting times and long exit times. Over the long time scales, we provide a description of how the distributions over joint action profiles transition from one cycle to another till it reaches the globally optimal state.

  15. Transient Response Analysis of Metropolis Learning in Games

    KAUST Repository

    Jaleel, Hassan; Shamma, Jeff S.

    2017-01-01

    The objective of this work is to provide a qualitative description of the transient properties of stochastic learning dynamics like adaptive play, log-linear learning, and Metropolis learning. The solution concept used in these learning dynamics for potential games is that of stochastic stability, which is based on the stationary distribution of the reversible Markov chain representing the learning process. However, time to converge to a stochastically stable state is exponential in the inverse of noise, which limits the use of stochastic stability as an effective solution concept for these dynamics. We propose a complete solution concept that qualitatively describes the state of the system at all times. The proposed concept is prevalent in control systems literature where a solution to a linear or a non-linear system has two parts, transient response and steady state response. Stochastic stability provides the steady state response of stochastic learning rules. In this work, we study its transient properties. Starting from an initial condition, we identify the subsets of the state space called cycles that have small hitting times and long exit times. Over the long time scales, we provide a description of how the distributions over joint action profiles transition from one cycle to another till it reaches the globally optimal state.

  16. Transient rheology of stimuli responsive hydrogels: Integrating microrheology and microfluidics

    Science.gov (United States)

    Sato, Jun

    Stimuli-responsive hydrogels have diverse potential applications in the field of drug delivery, tissue engineering, agriculture, cosmetics, gene therapy, and as sensors and actuators due to their unique responsiveness to external signals, such as pH, temperature, and ionic strength. Understanding the responsiveness of hydrogel structure and rheology to these stimuli is essential for designing materials with desirable performance. However, no instrumentation and well-defined methodology are available to characterize the structural and rheological responses to rapid solvent changes. In this thesis, a new microrheology set-up is described, which allows us to quantitatively measure the transient rheological properties and microstructure of a variety of solvent-responsive complex fluids. The device was constructed by integrating particle tracking microrheology and microfluidics and offers unique experimental capabilities for performing solvent-reponse measurements on soft fragile materials without applying external shear forces. Transient analysis methods to quantitatively obtain rheological properties were also constructed, and guidelines for the trade-off between statistical validity and temporal resolution were developed to accurately capture physical transitions. Employing the new device and methodology, we successfully quantified the transient rheological and microstructural responses during gel formation and break-up, and viscosity changes of solvent-responsive complex fluids. The analysis method was expanded for heterogeneous samples, incorporating methods to quantify the microrheology of samples with broad distributions of individual particle dynamics. Transient microrheology measurements of fragile, heterogeneous, self-assembled block copolypeptide hydrogels revealed that solvent exchange via convective mixing and dialysis can lead to significantly different gel properties and that commonly applied sample preparation protocols for the characterization of soft

  17. Delineation of diverse macrophage activation programs in response to intracellular parasites and cytokines.

    Directory of Open Access Journals (Sweden)

    Shuyi Zhang

    2010-03-01

    Full Text Available The ability to reside and proliferate in macrophages is characteristic of several infectious agents that are of major importance to public health, including the intracellular parasites Trypanosoma cruzi (the etiological agent of Chagas disease and Leishmania species (etiological agents of Kala-Azar and cutaneous leishmaniasis. Although recent studies have elucidated some of the ways macrophages respond to these pathogens, the relationships between activation programs elicited by these pathogens and the macrophage activation programs elicited by bacterial pathogens and cytokines have not been delineated.To provide a global perspective on the relationships between macrophage activation programs and to understand how certain pathogens circumvent them, we used transcriptional profiling by genome-wide microarray analysis to compare the responses of mouse macrophages following exposure to the intracellular parasites T. cruzi and Leishmania mexicana, the bacterial product lipopolysaccharide (LPS, and the cytokines IFNG, TNF, IFNB, IL-4, IL-10, and IL-17. We found that LPS induced a classical activation state that resembled macrophage stimulation by the Th1 cytokines IFNG and TNF. However, infection by the protozoan pathogen L. mexicana produced so few transcriptional changes that the infected macrophages were almost indistinguishable from uninfected cells. T. cruzi activated macrophages produced a transcriptional signature characterized by the induction of interferon-stimulated genes by 24 h post-infection. Despite this delayed IFN response by T. cruzi, the transcriptional response of macrophages infected by the kinetoplastid pathogens more closely resembled the transcriptional response of macrophages stimulated by the cytokines IL-4, IL-10, and IL-17 than macrophages stimulated by Th1 cytokines.This study provides global gene expression data for a diverse set of biologically significant pathogens and cytokines and identifies the relationships between

  18. Identification of Lactobacillus plantarum genes modulating the cytokine response of human peripheral blood mononuclear cells

    Directory of Open Access Journals (Sweden)

    Molenaar Douwe

    2010-11-01

    Full Text Available Abstract Background Modulation of the immune system is one of the most plausible mechanisms underlying the beneficial effects of probiotic bacteria on human health. Presently, the specific probiotic cell products responsible for immunomodulation are largely unknown. In this study, the genetic and phenotypic diversity of strains of the Lactobacillus plantarum species were investigated to identify genes of L. plantarum with the potential to influence the amounts of cytokines interleukin 10 (IL-10 and IL-12 and the ratio of IL-10/IL-12 produced by peripheral blood mononuclear cells (PBMCs. Results A total of 42 Lactobacillus plantarum strains isolated from diverse environmental and human sources were evaluated for their capacity to stimulate cytokine production in PBMCs. The L. plantarum strains induced the secretion of the anti-inflammatory cytokine IL-10 over an average 14-fold range and secretion of the pro-inflammatory cytokine IL-12 over an average 16-fold range. Comparisons of the strain-specific cytokine responses of PBMCs to comparative genome hybridization profiles obtained with L. plantarum WCFS1 DNA microarrays (also termed gene-trait matching resulted in the identification of 6 candidate genetic loci with immunomodulatory capacities. These loci included genes encoding an N-acetyl-glucosamine/galactosamine phosphotransferase system, the LamBDCA quorum sensing system, and components of the plantaricin (bacteriocin biosynthesis and transport pathway. Deletion of these genes in L. plantarum WCFS1 resulted in growth phase-dependent changes in the PBMC IL-10 and IL-12 cytokine profiles compared with wild-type cells. Conclusions The altered PBMC cytokine profiles obtained with the L. plantarum WCFS1 mutants were in good agreement with the predictions made by gene-trait matching for the 42 L. plantarum strains. This study therefore resulted in the identification of genes present in certain strains of L. plantarum which might be responsible for

  19. Impaired Cytokine Responses to Epstein-Barr Virus Antigens in Systemic Lupus Erythematosus Patients

    DEFF Research Database (Denmark)

    Draborg, Anette Holck; Sandhu, Noreen; Larsen, Nanna

    2016-01-01

    We analyzed cytokine responses against latent and lytic Epstein-Barr virus (EBV) antigens in systemic lupus erythematosus (SLE) patients and healthy controls (HCs) to obtain an overview of the distinctive immune regulatory response in SLE patients and to expand the previously determined impaired...

  20. Pattern recognition receptor-mediated cytokine response in infants across 4 continents.

    Science.gov (United States)

    Smolen, Kinga K; Ruck, Candice E; Fortuno, Edgardo S; Ho, Kevin; Dimitriu, Pedro; Mohn, William W; Speert, David P; Cooper, Philip J; Esser, Monika; Goetghebuer, Tessa; Marchant, Arnaud; Kollmann, Tobias R

    2014-03-01

    Susceptibility to infection as well as response to vaccination varies among populations. To date, the underlying mechanisms responsible for these clinical observations have not been fully delineated. Because innate immunity instructs adaptive immunity, we hypothesized that differences between populations in innate immune responses may represent a mechanistic link to variation in susceptibility to infection or response to vaccination. Determine whether differences in innate immune responses exist among infants from different continents of the world. We determined the innate cytokine response following pattern recognition receptor (PRR) stimulation of whole blood from 2-year-old infants across 4 continents (Africa, North America, South America, and Europe). We found that despite the many possible genetic and environmental exposure differences in infants across 4 continents, innate cytokine responses were similar for infants from North America, South America, and Europe. However, cells from South African infants secreted significantly lower levels of cytokines than did cells from infants from the 3 other sites, and did so following stimulation of extracellular and endosomal but not cytosolic PRRs. Substantial differences in innate cytokine responses to PRR stimulation exist among different populations of infants that could not have been predicted. Delineating the underlying mechanism(s) for these differences will not only aid in improving vaccine-mediated protection but possibly also provide clues for the susceptibility to infection in different regions of the world. Copyright © 2013 The Authors. Published by Mosby, Inc. All rights reserved.

  1. Cerebrospinal fluid (CSF) transient responses induced by hypercapnia

    International Nuclear Information System (INIS)

    Fisher, M.J.

    1984-01-01

    CSF transient responses to CO 2 inhalation were measured before and after facilitated perfusate flow through subarachnoid spaces of anesthetized cats during ventriculocisternal perfusion with artificial CSF containing 14 C-dextran. Convective mixing of perfusate in subarachnoid spaces was augmented while infusion constant, either by impeding cisternal efflux of perfusate by raising the cisternal outflow cannula (high CSF pressure), or by preventing CSF outflow by clamping the cisternal outflow cannula (stopflow; S-F). CSF transients were also measured before and after systemic administration of phenoxybenzamine (PBZ) in order to evaluate the contribution of sympatho-adrenergic activity to craniospinal CSF redistribution and mixing. Results from high CSF pressure and S-F experiments indicate that unequilibrated CSF contributes significantly to the reduced tracer concentration in CSF volume (Vd) since SCF effluent tracer concentration (Cd) was decreased after subarachnoid facilitated flow. Further, results from S-F studies indicate that at least 50% of Cd is due to craniospinal fluid redistribution, a process which, along with CSF outflow transients, was unaffected by PBZ. Conversely, PBZ administration decreased steady state SCF formation and absorption through alpha-mediated cerebrovascular responses and/or through beta-adrenoceptor inhibition of metabolism of CSF secretory epithelium

  2. System transient response to loss of off-site power

    International Nuclear Information System (INIS)

    Sozer, A.

    1990-01-01

    A simultaneous trip of the reactor, main circulation pumps, secondary coolant pumps, and pressurizer pump due to loss of off-site power at the High Flux Isotope Reactor (HFIR) located at the Oak Ridge National Laboratory (ORNL) has been analyzed to estimate available safety margin. A computer model based on the Modular Modeling System code has been used to calculate the transient response of the system. The reactor depressurizes from 482.7 psia down to about 23 psia in about 50 seconds and remains stable thereafter. Available safety margin has been estimated in terms of the incipient boiling heat flux ratio. It is a conservative estimate due to assumed less than available primary and secondary flows and higher than normal depressurization rate. The ratio indicates no incipient boiling conditions at the hot spot. No potential damage to the fuel is likely to occur during this transient. 2 refs., 6 figs

  3. Transient cardio-respiratory responses to visually induced tilt illusions

    Science.gov (United States)

    Wood, S. J.; Ramsdell, C. D.; Mullen, T. J.; Oman, C. M.; Harm, D. L.; Paloski, W. H.

    2000-01-01

    Although the orthostatic cardio-respiratory response is primarily mediated by the baroreflex, studies have shown that vestibular cues also contribute in both humans and animals. We have demonstrated a visually mediated response to illusory tilt in some human subjects. Blood pressure, heart and respiration rate, and lung volume were monitored in 16 supine human subjects during two types of visual stimulation, and compared with responses to real passive whole body tilt from supine to head 80 degrees upright. Visual tilt stimuli consisted of either a static scene from an overhead mirror or constant velocity scene motion along different body axes generated by an ultra-wide dome projection system. Visual vertical cues were initially aligned with the longitudinal body axis. Subjective tilt and self-motion were reported verbally. Although significant changes in cardio-respiratory parameters to illusory tilts could not be demonstrated for the entire group, several subjects showed significant transient decreases in mean blood pressure resembling their initial response to passive head-up tilt. Changes in pulse pressure and a slight elevation in heart rate were noted. These transient responses are consistent with the hypothesis that visual-vestibular input contributes to the initial cardiovascular adjustment to a change in posture in humans. On average the static scene elicited perceived tilt without rotation. Dome scene pitch and yaw elicited perceived tilt and rotation, and dome roll motion elicited perceived rotation without tilt. A significant correlation between the magnitude of physiological and subjective reports could not be demonstrated.

  4. Stratum corneum cytokines and skin irritation response to sodium lauryl sulfate.

    Science.gov (United States)

    De Jongh, Cindy M; Verberk, Maarten M; Withagen, Carien E T; Jacobs, John J L; Rustemeyer, Thomas; Kezic, Sanja

    2006-06-01

    Little is known about cytokines involved in chronic irritant contact dermatitis. Individual cytokine profiles might explain at least part of the differences in the individual response to irritation. Our objective was to investigate the relation between baseline stratum corneum (SC) cytokine levels and the skin response to a single and a repeated irritation test. This study also aimed to determine changes in SC cytokine levels after repeated irritation. Transepidermal water loss (TEWL) and erythema were measured in 20 volunteers after single 24-hr exposure to 1% sodium lauryl sulfate (SLS), and during and after repeated exposure to 0.1% SLS over a 3-week period. SC cytokine levels were measured from an unexposed skin site and from the repeatedly exposed site. Interleukin (IL)-1alpha decreased by 30% after repeated exposure, while IL-1RA increased 10-fold and IL-8 increased fourfold. Baseline IL-1RA and IL-8 values were predictors of TEWL and erythema after single exposure (r = 0.55-0.61). 6 subjects showed barrier recovery during repeated exposure. Baseline IL-1RA and IL-8 levels are likely to be indicators of higher skin irritability after single exposure to SLS. Barrier repair in some of the subjects might explain the lack of agreement between the TEWL response after single and repeated irritation.

  5. Nonstationary Transient Vibroacoustic Response of a Beam Structure

    Science.gov (United States)

    Caimi, R. E.; Margasahayam, R. N.; Nayfeh, Jamal F.

    1997-01-01

    This study consists of an investigation into the nonstationary transient response of the Verification Test Article (VETA) when subjected to random acoustic excitation. The goal is to assess excitation models that can be used in the design of structures and equipment when knowledge of the structure and the excitation is limited. The VETA is an instrumented cantilever beam that was exposed to acoustic loading during five Space Shuttle launches. The VETA analytical structural model response is estimated using the direct averaged power spectral density and the normalized pressure spectra methods. The estimated responses are compared to the measured response of the VETA. These comparisons are discussed with a focus on prediction conservatism and current design practice.

  6. Fuel pin response to an overpower transient in an LMFBR

    International Nuclear Information System (INIS)

    Grosberg, A.J.; Head, J.L.

    1979-01-01

    This paper describes a method by which the ability of a whole-core code accurately to predict the time and location of the first fuel pin failures may be tested. The method involves the use of a relatively simple whole-core code to 'drive' a sophisticated fuel pin code, which is far too complex to be used within a whole-core code but which is potentially capable of modelling reliably the response of an individual fuel pin. The method cannot follow accurately the subsequent course of the transient because the simple whole-core code does not model the reactivity effects of events which may follow pin failure. The codes used were the simple whole-core code FUTURE and the fuel pin behaviour code FRUMP. The paper describes an application of the method to analyse a hypothetical LMFBR accident in which the control rods were assumed to be driven from the core at maximum speed, with all trip circuits failed. Taking 0.5% clad strain as a clad failure criterion, failure was predicted to occur at the top of the active core at about 10s into the transient. A repeat analysis, using an alternative clad yield criterion which is thought to be more realistic, indicated failure at the same position but 24s into the transient. This is after the onset of sodium boiling. Pin failure at the top of the core are likely to cause negative reactivity changes. In this hypothetical accident, pin failures are likely, therefore, to have a moderating effect on the course of the transient. (orig.)

  7. Dual function of CD70 in viral infection: modulator of early cytokine responses and activator of adaptive responses1

    OpenAIRE

    Allam, Atef; Swiecki, Melissa; Vermi, William; Ashwell, Jonathan D.; Colonna, Marco

    2014-01-01

    The role of the tumor necrosis factor family member CD70 in adaptive T cell responses has been intensively studied but its function in innate responses is still under investigation. Here we show that CD70 inhibits the early innate response to murine cytomegalovirus (MCMV) but is essential for the optimal generation of virus-specific CD8 T cells. CD70-/- mice reacted to MCMV infection with a robust type I interferon and proinflammatory cytokine response. This response was sufficient for initia...

  8. Transient response of the 'multiple water-bag' plasma

    International Nuclear Information System (INIS)

    Lim Cheeseng

    1989-01-01

    A charge activates impulsively and then decays temporally within a MWB (multiple water-bag)-modelled warm plasma. The transient problem is formulated and asymptotically resolved for large time. The response potential comprises two characteristically distinct quantities W and W N : W is a superposition of spherically expanding, moderately attenuated Kelvin waves contributed by certain points on a subset of dispersion curves; W N is a superposition, associated with two other dispersion curves, of three spherical wavefunctions, one of which incorporates the Fresnel integrals. A transient state feature of the MWB discretization is the partitioning of the response field by growing (fast) fronts, (trailing) slow caustics and a j -surfaces, the fastest among these being an a N- surface (thermal front) which pushes back a quasi-static exterior. Contrary to expectations, there is no response jump across any of those growing partitions. Wavefunctions near the slow caustics possess Airy factors. A rest state ultimately develops behind the slowest slow caustic. An application is made to the fluid plasma. (author)

  9. Cytokine balance in human malaria: does Plasmodium vivax elicit more inflammatory responses than Plasmodium falciparum?

    Directory of Open Access Journals (Sweden)

    Raquel M Gonçalves

    Full Text Available BACKGROUND: The mechanisms by which humans regulate pro- and anti-inflammatory responses on exposure to different malaria parasites remains unclear. Although Plasmodium vivax usually causes a relatively benign disease, this parasite has been suggested to elicit more host inflammation per parasitized red blood cell than P. falciparum. METHODOLOGY/PRINCIPAL FINDINGS: We measured plasma concentrations of seven cytokines and two soluble tumor necrosis factor (TNF-α receptors, and evaluated clinical and laboratory outcomes, in Brazilians with acute uncomplicated infections with P. vivax (n = 85, P. falciparum (n = 30, or both species (n = 12, and in 45 asymptomatic carriers of low-density P. vivax infection. Symptomatic vivax malaria patients, compared to those infected with P. falciparum or both species, had more intense paroxysms, but they had no clear association with a pro-inflammatory imbalance. To the contrary, these patients had higher levels of the regulatory cytokine interleukin (IL-10, which correlated positively with parasite density, and elevated IL-10/TNF-α, IL-10/interferon (IFN-γ, IL-10/IL-6 and sTNFRII/TNF-α ratios, compared to falciparum or mixed-species malaria patient groups. Vivax malaria patients had the highest levels of circulating soluble TNF-α receptor sTNFRII. Levels of regulatory cytokines returned to normal values 28 days after P. vivax clearance following chemotherapy. Finally, asymptomatic carriers of low P. vivax parasitemias had substantially lower levels of both inflammatory and regulatory cytokines than did patients with clinical malaria due to either species. CONCLUSIONS: Controlling fast-multiplying P. falciparum blood stages requires a strong inflammatory response to prevent fulminant infections, while reducing inflammation-related tissue damage with early regulatory cytokine responses may be a more cost-effective strategy in infections with the less virulent P. vivax parasite. The early induction

  10. Cytokine profiles show heterogeneity of interferon-β response in multiple sclerosis patients

    DEFF Research Database (Denmark)

    Hegen, Harald; Adrianto, Indra; Lessard, Christopher J

    2016-01-01

    OBJECTIVE: To evaluate serum cytokine profiles for their utility to determine the heterogeneous responses to interferon (IFN)-β treatment in patients with multiple sclerosis (MS). METHODS: Patients with relapsing-remitting MS (RRMS) or clinically isolated syndrome receiving de novo IFN-β treatment...... were included in this prospective, observational study. Number of relapses and changes in disability were assessed 2 years prior to and 2 years after initiation of treatment. Sera were collected at baseline and after 3 months on therapy. Cytokine levels in sera were assessed by Luminex multiplex assays...

  11. Impaired cytokine responses in patients with cryopyrin-associated periodic syndrome (CAPS).

    Science.gov (United States)

    Haverkamp, M H; van de Vosse, E; Goldbach-Mansky, R; Holland, S M

    2014-09-01

    Cryopyrin-associated periodic syndrome (CAPS) is characterized by dysregulated inflammation with excessive interleukin (IL)-1β activation and secretion. Neonatal-onset multi-system inflammatory disease (NOMID) is the most severe form. We explored cytokine responses in 32 CAPS patients before and after IL-1β blocking therapy. We measured cytokines produced by activated peripheral blood monuclear cells (PBMCs) from treated and untreated CAPS patients after stimulation for 48 h with phytohaemagglutinin (PHA), PHA plus IL-12, lipopolysaccharide (LPS) or LPS plus interferon (IFN)-γ. We measured IL-1β, IL-6, IL-10, tumour necrosis factor (TNF), IL-12p70 and IFN-γ in the supernatants. PBMCs from three untreated CAPS patients were cultured in the presence of the IL-1β blocker Anakinra. Fifty healthy individuals served as controls. CAPS patients had high spontaneous production of IL-1β, IL-6, TNF and IFN-γ by unstimulated cells. However, stimulation indexes (SIs, ratio of stimulated to unstimulated production) of these cytokines to PHA and LPS were low in NOMID patients compared to controls. Unstimulated IL-10 and IL-12p70 production was normal, but up-regulation after PHA and LPS was also low. LPS plus IFN-γ inadequately up-regulated the production of IL-1β, IL-6, TNF and IL-10 in CAPS patients. In-vitro but not in-vivo treatment with Anakinra improved SIs by lowering spontaneous cytokine production. However, in-vitro treatment did not improve the low stimulated cytokine levels. Activating mutations in NLRP3 in CAPS are correlated with poor SIs to PHA, LPS and IFN-γ. The impairment in stimulated cytokine responses in spite of IL-1β blocking therapy suggests a broader intrinsic defect in CAPS patients, which is not corrected by targeting IL-1β. © 2014 British Society for Immunology.

  12. Transient response of nonlinear polymer networks: A kinetic theory

    Science.gov (United States)

    Vernerey, Franck J.

    2018-06-01

    Dynamic networks are found in a majority of natural materials, but also in engineering materials, such as entangled polymers and physically cross-linked gels. Owing to their transient bond dynamics, these networks display a rich class of behaviors, from elasticity, rheology, self-healing, or growth. Although classical theories in rheology and mechanics have enabled us to characterize these materials, there is still a gap in our understanding on how individuals (i.e., the mechanics of each building blocks and its connection with others) affect the emerging response of the network. In this work, we introduce an alternative way to think about these networks from a statistical point of view. More specifically, a network is seen as a collection of individual polymer chains connected by weak bonds that can associate and dissociate over time. From the knowledge of these individual chains (elasticity, transient attachment, and detachment events), we construct a statistical description of the population and derive an evolution equation of their distribution based on applied deformation and their local interactions. We specifically concentrate on nonlinear elastic response that follows from the strain stiffening response of individual chains of finite size. Upon appropriate averaging operations and using a mean field approximation, we show that the distribution can be replaced by a so-called chain distribution tensor that is used to determine important macroscopic measures such as stress, energy storage and dissipation in the network. Prediction of the kinetic theory are then explored against known experimental measurement of polymer responses under uniaxial loading. It is found that even under the simplest assumptions of force-independent chain kinetics, the model is able to reproduce complex time-dependent behaviors of rubber and self-healing supramolecular polymers.

  13. Grounding line transient response in marine ice sheet models

    Directory of Open Access Journals (Sweden)

    A. S. Drouet

    2013-03-01

    Full Text Available Marine ice-sheet stability is mostly controlled by the dynamics of the grounding line, i.e. the junction between the grounded ice sheet and the floating ice shelf. Grounding line migration has been investigated within the framework of MISMIP (Marine Ice Sheet Model Intercomparison Project, which mainly aimed at investigating steady state solutions. Here we focus on transient behaviour, executing short-term simulations (200 yr of a steady ice sheet perturbed by the release of the buttressing restraint exerted by the ice shelf on the grounded ice upstream. The transient grounding line behaviour of four different flowline ice-sheet models has been compared. The models differ in the physics implemented (full Stokes and shallow shelf approximation, the numerical approach, as well as the grounding line treatment. Their overall response to the loss of buttressing is found to be broadly consistent in terms of grounding line position, rate of surface elevation change and surface velocity. However, still small differences appear for these latter variables, and they can lead to large discrepancies (> 100% observed in terms of ice sheet contribution to sea level when cumulated over time. Despite the recent important improvements of marine ice-sheet models in their ability to compute steady state configurations, our results question the capacity of these models to compute short-term reliable sea-level rise projections.

  14. Immunologic Characterization of Cytokine Responses to Enterovirus 71 and Coxsackievirus A16 Infection in Children.

    Science.gov (United States)

    Zhang, Shu-Yan; Xu, Mei-Yan; Xu, Hong-Mei; Li, Xiu-Jun; Ding, Shu-Jun; Wang, Xian-Jun; Li, Ting-Yu; Lu, Qing-Bin

    2015-07-01

    Viral encephalitis is a serious complication of hand, foot, and mouth disease (HFMD), but characteristics of cytokines response in enterovirus 71 (EV-71) and/or coxsackievirus A16 (CV-A16) associated HFMD with or without viral encephalitis remained unclear.We performed a multigroup retrospective study and compared the serum cytokines concentrations among 16 encephalitis patients infected with EV-71 and CV-A16, 24 encephalitis patients with single EV-71 infection, 34 mild HFMD patients with EV-71 infection, 18 mild HFMD patients with CV-A16 infection, and 39 healthy control subjects.Serum levels of interleukin (IL)-4, IL-5, IL-22, and IL-23 were significantly higher in encephalitis patients than in HFMD-alone patients when adjusting for age and sex; IL-2, tumor necrosis factor (TNF)-α, IL-4, IL-22, and IL-1β were significantly higher in HFMD-alone patients of EV-71 infection than in CV-A16 infected HFMD patients; cerebrospinal fluid level of IL-6 was lower in the EV-71/CV-A16 associated encephalitis than that in the EV-71 alone associated encephalitis patients.Over or low expression of the cytokines cascade in HFMD patients appears to play an important role in the elicitation of the immune response to EV-71 and CV-A16. These data will be used to define a cytokine profile, which might help to recognize HFMD patients with the high risk of developing encephalitis.

  15. Monitoring bottlenose dolphin leukocyte cytokine mRNA responsiveness by qPCR

    Science.gov (United States)

    Eberle, Kirsten C.; Venn-Watson, Stephanie K.; Jensen, Eric D.; Porter, Tracy J.; Waters, Theresa E.; Sacco, Randy E.

    2017-01-01

    Both veterinarians caring for dolphins in managed populations and researchers monitoring wild populations use blood-based diagnostics to monitor bottlenose dolphin (Tursiops truncatus) health. Quantitative PCR (qPCR) can be used to assess cytokine transcription patterns of peripheral blood mononuclear cells (PBMC). This can supplement currently available blood tests with information on immune status. Full realization of this potential requires establishment of normal ranges of cytokine gene transcription levels in bottlenose dolphins. We surveyed four dolphins over the span of seven months by serial bleeds. PBMC were stimulated with phytohaemagglutinin (1, 5, and 10 μg/mL) and concanavalin A (1 μg/mL) for 48 H in vitro. RNA from these cultures was probed by qPCR using Tursiops truncatus-specific primers (IL-1α, IL-1β, IL-1RA, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p40, IL-13, IL-18, IFN-γ and TNF-α). Two blood samples from an additional bottlenose dolphin diagnosed with acute pulmonary disease add further perspective to the data. We observed that mitogen choice made a significant difference in the magnitude of gene transcription observed. On the other hand, most cytokines tested exhibited limited intra-animal variation. However, IL-6 and IL-12p40 differed between older and younger dolphins. Furthermore, the magnitude of mitogenic response clusters the tested cytokines into three groups. The data provide a reference for the selection of target cytokine mRNAs and their expected range of mitogen-stimulated cytokine gene transcription for future studies. PMID:29272269

  16. Monitoring bottlenose dolphin leukocyte cytokine mRNA responsiveness by qPCR.

    Directory of Open Access Journals (Sweden)

    Amelia Ruth Hofstetter

    Full Text Available Both veterinarians caring for dolphins in managed populations and researchers monitoring wild populations use blood-based diagnostics to monitor bottlenose dolphin (Tursiops truncatus health. Quantitative PCR (qPCR can be used to assess cytokine transcription patterns of peripheral blood mononuclear cells (PBMC. This can supplement currently available blood tests with information on immune status. Full realization of this potential requires establishment of normal ranges of cytokine gene transcription levels in bottlenose dolphins. We surveyed four dolphins over the span of seven months by serial bleeds. PBMC were stimulated with phytohaemagglutinin (1, 5, and 10 μg/mL and concanavalin A (1 μg/mL for 48 H in vitro. RNA from these cultures was probed by qPCR using Tursiops truncatus-specific primers (IL-1α, IL-1β, IL-1RA, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p40, IL-13, IL-18, IFN-γ and TNF-α. Two blood samples from an additional bottlenose dolphin diagnosed with acute pulmonary disease add further perspective to the data. We observed that mitogen choice made a significant difference in the magnitude of gene transcription observed. On the other hand, most cytokines tested exhibited limited intra-animal variation. However, IL-6 and IL-12p40 differed between older and younger dolphins. Furthermore, the magnitude of mitogenic response clusters the tested cytokines into three groups. The data provide a reference for the selection of target cytokine mRNAs and their expected range of mitogen-stimulated cytokine gene transcription for future studies.

  17. Effect of praziquantel treatment during pregnancy on cytokine responses to schistosome antigens

    DEFF Research Database (Denmark)

    Tweyongyere, Robert; Mawa, Patrice A.; Ngom-Wegi, Sophy

    2008-01-01

    . Cytokine responses to S. mansoni worm and egg antigens were measured in whole blood culture before and 6 weeks after each treatment. RESULTS: Schistosome-specific cytokine responses were suppressed during pregnancy. Praziquantel treatment during pregnancy caused significant boosts in interferon-gamma (IFN......Praziquantel treatment of schistosomiasis boosts antischistosome responses, with type 2 helper T cell bias that may contribute to immunologically mediated killing and to protection against reinfection. Praziquantel treatment during pregnancy was recommended in 2002, but the immunological effects...... of the treatment had not been investigated. METHODS: A cohort of 387 Schistosoma mansoni-infected women were recruited from a larger trial of deworming during pregnancy. Women were randomized to receive either praziquantel or placebo during pregnancy. Six weeks after delivery, all women received praziquantel...

  18. Mucorales spores induce a proinflammatory cytokine response in human mononuclear phagocytes and harbor no rodlet hydrophobins.

    Science.gov (United States)

    Wurster, Sebastian; Thielen, Vanessa; Weis, Philipp; Walther, Paul; Elias, Johannes; Waaga-Gasser, Ana Maria; Dragan, Mariola; Dandekar, Thomas; Einsele, Hermann; Löffler, Jürgen; Ullmann, Andrew J

    2017-11-17

    Mucormycoses are life-threatening infections in immunocompromised patients. This study characterizes the response of human mononuclear cells to different Mucorales and Ascomycota. PBMC, monocytes, and monocyte derived dendritic cells (moDCs) from healthy donors were stimulated with resting and germinated stages of Mucorales and Ascomycota. Cytokine response and expression of activation markers were studied. Both inactivated germ tubes and resting spores of Rhizopus arrhizus and other human pathogenic Mucorales species significantly stimulated mRNA synthesis and secretion of proinflammatory cytokines. Moreover, R. arrhizus spores induced the upregulation of co-stimulatory molecules on moDCs and a specific T-helper cell response. Removal of rodlet hydrophobins by hydrofluoric acid treatment of A. fumigatus conidia resulted in enhanced immunogenicity, whereas the cytokine response of PBMCs to dormant R. arrhizus spores was not influenced by hydrofluoric acid. Scanning electron micrographs of Mucorales spores did not exhibit any morphological correlates of rodlet hydrophobins. Taken together, this study revealed striking differences in the response of human mononuclear cells to resting stages of Ascomycota and Mucorales, which may be explained by absence of an immunoprotective hydrophobin layer in Mucorales spores.

  19. The Multiscale Material Point Method for Simulating Transient Responses

    Science.gov (United States)

    Chen, Zhen; Su, Yu-Chen; Zhang, Hetao; Jiang, Shan; Sewell, Thomas

    2015-06-01

    To effectively simulate multiscale transient responses such as impact and penetration without invoking master/slave treatment, the multiscale material point method (Multi-MPM) is being developed in which molecular dynamics at nanoscale and dissipative particle dynamics at mesoscale might be concurrently handled within the framework of the original MPM at microscale (continuum level). The proposed numerical scheme for concurrently linking different scales is described in this paper with simple examples for demonstration. It is shown from the preliminary study that the mapping and re-mapping procedure used in the original MPM could coarse-grain the information at fine scale and that the proposed interfacial scheme could provide a smooth link between different scales. Since the original MPM is an extension from computational fluid dynamics to solid dynamics, the proposed Multi-MPM might also become robust for dealing with multiphase interactions involving failure evolution. This work is supported in part by DTRA and NSFC.

  20. Dual function of CD70 in viral infection: modulator of early cytokine responses and activator of adaptive responses1

    Science.gov (United States)

    Allam, Atef; Swiecki, Melissa; Vermi, William; Ashwell, Jonathan D.; Colonna, Marco

    2014-01-01

    The role of the tumor necrosis factor family member CD70 in adaptive T cell responses has been intensively studied but its function in innate responses is still under investigation. Here we show that CD70 inhibits the early innate response to murine cytomegalovirus (MCMV) but is essential for the optimal generation of virus-specific CD8 T cells. CD70-/- mice reacted to MCMV infection with a robust type I interferon and proinflammatory cytokine response. This response was sufficient for initial control of MCMV, although at later time points, CD70-/- mice became more susceptible to MCMV infection. The heightened cytokine response during the early phase of MCMV infection in CD70-/- mice was paralleled by a reduction in regulatory T cells (Treg). Treg from naïve CD70-/- mice were not as efficient at suppressing T cell proliferation compared to Treg from naïve WT mice and depletion of Treg during MCMV infection in Foxp3-DTR mice or in WT mice recapitulated the phenotype observed in CD70-/- mice. Our study demonstrates that while CD70 is required for the activation of the antiviral adaptive response, it has a regulatory role in early cytokine responses to viruses such as MCMV, possibly through maintenance of Treg survival and function. PMID:24913981

  1. Cytokine responses in relation to age, gender, body mass index, Mycobacterium tuberculosis infection, and otitis media among inuit in greenland

    DEFF Research Database (Denmark)

    Nielsen, Nina Odgaard; Soborg, Bolette; Børresen, Malene

    2013-01-01

    To evaluate the cytokine response pattern in Inuit in Greenland in relation to age, gender, body mass index (BMI), Mycobacterium tuberculosis infection (MTI), and otitis media (OM) to assess whether Inuit may have signs of impaired immune responsiveness to infection.......To evaluate the cytokine response pattern in Inuit in Greenland in relation to age, gender, body mass index (BMI), Mycobacterium tuberculosis infection (MTI), and otitis media (OM) to assess whether Inuit may have signs of impaired immune responsiveness to infection....

  2. Cytokine profiles in tears accompanying the secondary conjunctival responses induced by nasal allergy.

    Science.gov (United States)

    Pelikan, Zdenek

    2014-02-01

    Allergic conjunctivitis (AC) occurs either in a primary form, due to the allergic reaction localized in the conjunctivae or in a secondary form, induced by an allergic reaction initiated primarily in the nasal mucosa. The purpose of this study was to investigate the cytokine profiles in tears associated with the secondary conjunctival response (SCR) types. In 47 AC patients developing 16 immediate (SICR; p tears. The SCRs were associated with significant concentration changes of particular cytokines in tears (p tears during the phosphate-buffered saline controls or negative SCRs. Different cytokine profiles in the tears accompanying the immediate, late and delayed types of SCR, induced by nasal allergy, would indicate involvement of different hypersensitivity mechanisms in the particular SCR types. The low cytokine concentrations in tears recorded during the SCRs may suggest their origin from the nasal mucosa. These results emphasize the diagnostic value of NPTs with allergens combined with monitoring of various ocular features in patients suffering from the secondary form of AC. These results may also have an impact on the therapeutical approach to this clinical entity.

  3. Cytokines in tears during the secondary keratoconjunctival responses induced by allergic reaction in the nasal mucosa.

    Science.gov (United States)

    Pelikan, Zdenek

    2014-01-01

    Allergic keratoconjunctivitis (KC) can occur in a primary form due to an allergic reaction taking place in the conjunctivae or in a secondary form induced by nasal allergy. To search for the cytokine changes in tears accompanying the secondary keratoconjunctival response types (SKCR), caused by the nasal allergy. In 43 KC patients developing 15 immediate (SIKCR), 16 late (SLKCR) and 12 delayed (SDYKCR) responses to nasal provocation tests with allergens (NPT), the NPTs were repeated with subsequent recording of cytokine concentrations in tears up to 72 h. The SIKCRs (ptears, suggesting involvement of different hypersensitivity mechanisms. These results also stress the diagnostic usefulness of NPTs combined with monitoring of ocular features in KC patients who did not respond satisfactorily to the topical ophthalmological treatment. © 2014 S. Karger AG, Basel.

  4. The peri-operative cytokine response in infants and young children following major surgery

    DEFF Research Database (Denmark)

    Hansen, Tom Giedsing; Tønnesen, Else Kirstine; Andersen, J B

    1998-01-01

    The peri-operative cytokine response was studied in 13 infants and young children undergoing major surgery. All children were anaesthetized with a combined general and epidural anaesthetic technique, followed by post-operative epidural analgesia with bupivacaine and fentanyl. Blood samples were...... taken before and after surgery, 24 h post-operatively, and finally, when the children were mobilized and had regained gastrointestinal function. Plasma samples were analysed for tumour necrosis factor-alpha, interleukin-1 alpha, interleukin-1 beta, interleukin-6, interferon-gamma, interleukin-10...... and the interleukin-1 receptor antagonist. The cytokine responses were highly variable. Overall, no significant changes between pre- and post-operative plasma concentrations were found. Tumour necrosis factor-alpha and the interleukin-1 receptor antagonist were detectable in all children, and a trend towards an early...

  5. Cytokine Responses in Gills of Capoeta umbla as Biomarkers of Environmental Pollution.

    Science.gov (United States)

    Danabas, Durali; Yildirim, Nuran Cikcikoglu; Yildirim, Numan; Onal, Ayten Oztufekci; Uslu, Gulsad; Unlu, Erhan; Danabas, Seval; Ergin, Cemil; Tayhan, Nilgun

    2016-03-01

    Immunological biomarkers reflect the effects of exposure to environmental contaminants. In this study, the suitability and sensitivity of cytokine responses, interleukin1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α) in gill tissues of Capoeta umbla (Heckel, 1843), collected from different regions, as early warning indices of environmental pollution and ecosystem health was evaluated. Fish and water samples were taken from ten stations in March and September 2011 and 2012. Tumor necrosis factor-α, IL-1β and IL-6 levels were determined in samples of the gill tissues by using an ELISA kit. Significant variations of TNF-α, IL-1β and IL-6 levels observed between stations and seasons. The results of this study show that seasonal variations of cytokine responses in gills of Capoeta umbla are sensitive to the contaminants present in Uzuncayir Dam Lake (Tunceli, Turkey) water and are valuable biomarkers for environmental pollution and ecosystem health.

  6. Differing House Finch Cytokine Expression Responses to Original and Evolved Isolates of Mycoplasma gallisepticum

    Directory of Open Access Journals (Sweden)

    Michal Vinkler

    2018-01-01

    Full Text Available The recent emergence of the poultry bacterial pathogen Mycoplasma gallisepticum (MG in free-living house finches (Haemorhous mexicanus, which causes mycoplasmal conjunctivitis in this passerine bird species, resulted in a rapid coevolutionary arms-race between MG and its novel avian host. Despite extensive research on the ecological and evolutionary dynamics of this host–pathogen system over the past two decades, the immunological responses of house finches to MG infection remain poorly understood. We developed seven new probe-based one-step quantitative reverse transcription polymerase chain reaction assays to investigate mRNA expression of house finch cytokine genes (IL1B, IL6, IL10, IL18, TGFB2, TNFSF15, and CXCLi2, syn. IL8L. These assays were then used to describe cytokine transcription profiles in a panel of 15 house finch tissues collected at three distinct time points during MG infection. Based on initial screening that indicated strong pro-inflammatory cytokine expression during MG infection at the periorbital sites in particular, we selected two key house finch tissues for further characterization: the nictitating membrane, i.e., the internal eyelid in direct contact with MG, and the Harderian gland, the secondary lymphoid tissue responsible for regulation of periorbital immunity. We characterized cytokine responses in these two tissues for 60 house finches experimentally inoculated either with media alone (sham or one of two MG isolates: the earliest known pathogen isolate from house finches (VA1994 or an evolutionarily more derived isolate collected in 2006 (NC2006, which is known to be more virulent. We show that the more derived and virulent isolate NC2006, relative to VA1994, triggers stronger local inflammatory cytokine signaling, with peak cytokine expression generally occurring 3–6 days following MG inoculation. We also found that the extent of pro-inflammatory interleukin 1 beta signaling was correlated with conjunctival

  7. Differing House Finch Cytokine Expression Responses to Original and Evolved Isolates of Mycoplasma gallisepticum.

    Science.gov (United States)

    Vinkler, Michal; Leon, Ariel E; Kirkpatrick, Laila; Dalloul, Rami A; Hawley, Dana M

    2018-01-01

    The recent emergence of the poultry bacterial pathogen Mycoplasma gallisepticum (MG) in free-living house finches ( Haemorhous mexicanus ), which causes mycoplasmal conjunctivitis in this passerine bird species, resulted in a rapid coevolutionary arms-race between MG and its novel avian host. Despite extensive research on the ecological and evolutionary dynamics of this host-pathogen system over the past two decades, the immunological responses of house finches to MG infection remain poorly understood. We developed seven new probe-based one-step quantitative reverse transcription polymerase chain reaction assays to investigate mRNA expression of house finch cytokine genes ( IL1B, IL6, IL10, IL18, TGFB2, TNFSF15 , and CXCLi2 , syn. IL8L ). These assays were then used to describe cytokine transcription profiles in a panel of 15 house finch tissues collected at three distinct time points during MG infection. Based on initial screening that indicated strong pro-inflammatory cytokine expression during MG infection at the periorbital sites in particular, we selected two key house finch tissues for further characterization: the nictitating membrane, i.e., the internal eyelid in direct contact with MG, and the Harderian gland, the secondary lymphoid tissue responsible for regulation of periorbital immunity. We characterized cytokine responses in these two tissues for 60 house finches experimentally inoculated either with media alone (sham) or one of two MG isolates: the earliest known pathogen isolate from house finches (VA1994) or an evolutionarily more derived isolate collected in 2006 (NC2006), which is known to be more virulent. We show that the more derived and virulent isolate NC2006, relative to VA1994, triggers stronger local inflammatory cytokine signaling, with peak cytokine expression generally occurring 3-6 days following MG inoculation. We also found that the extent of pro-inflammatory interleukin 1 beta signaling was correlated with conjunctival MG loads

  8. Associations between cytokines, endocrine stress response, and gastrointestinal symptoms in autism spectrum disorder

    OpenAIRE

    Ferguson, Bradley J.; Marler, Sarah; Altstein, Lily L.; Lee, Evon Batey; Mazurek, Micah O.; McLaughlin, Aaron; Macklin, Eric A.; McDonnell, Erin; Davis, Daniel J.; Belenchia, Anthony M.; Gillespie, Catherine H.; Peterson, Catherine A.; Bauman, Margaret L.; Margolis, Kara Gross; Veenstra-VanderWeele, Jeremy

    2016-01-01

    Many children and adolescents with autism spectrum disorder (ASD) have significant gastrointestinal (GI) symptoms, but the etiology is currently unknown. Some individuals with ASD show altered reactivity to stress and altered immune markers relative to typically-developing individuals, particularly stress-responsive cytokines including tumor necrosis factor alpha (TNF-?) and interleukin 6 (IL-6). Acute and chronic stress is associated with the onset and exacerbation of GI symptoms in those wi...

  9. Electromagnetic Transient Response Analysis of DFIG under Cascading Grid Faults Considering Phase Angel Jumps

    DEFF Research Database (Denmark)

    Wang, Yun; Wu, Qiuwei

    2014-01-01

    This paper analysis the electromagnetic transient response characteristics of DFIG under symmetrical and asymmetrical cascading grid fault conditions considering phaseangel jump of grid. On deriving the dynamic equations of the DFIG with considering multiple constraints on balanced and unbalanced...... conditions, phase angel jumps, interval of cascading fault, electromagnetic transient characteristics, the principle of the DFIG response under cascading voltage fault can be extract. The influence of grid angel jump on the transient characteristic of DFIG is analyzed and electromagnetic response...

  10. Epithelial cell pro-inflammatory cytokine response differs across dental plaque bacterial species.

    Science.gov (United States)

    Stathopoulou, Panagiota G; Benakanakere, Manjunatha R; Galicia, Johnah C; Kinane, Denis F

    2010-01-01

    The dental plaque is comprised of numerous bacterial species, which may or may not be pathogenic. Human gingival epithelial cells (HGECs) respond to perturbation by various bacteria of the dental plaque by production of different levels of inflammatory cytokines, which is a putative reflection of their virulence. The aim of the current study was to determine responses in terms of interleukin (IL)-1beta, IL-6, IL-8 and IL-10 secretion induced by Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, Fusobacterium nucleatum and Streptococcus gordonii in order to gauge their virulence potential. HGECs were challenged with the four bacterial species, live or heat killed, at various multiplicity of infections and the elicited IL-1beta, IL-6, IL-8 and IL-10 responses were assayed by enzyme-linked immunosorbent assay. Primary HGECs challenged with live P. gingivalis produced high levels of IL-1beta, while challenge with live A. actinomycetemcomitans gave high levels of IL-8. The opportunistic pathogen F. nucleatum induces the highest levels of pro-inflammatory cytokines, while the commensal S. gordonii is the least stimulatory. We conclude that various dental plaque biofilm bacteria induce different cytokine response profiles in primary HGECs that may reflect their individual virulence or commensal status.

  11. Whole-body irradiation transiently diminishes the adrenocorticotropin response to recombinant human interleukin-1{alpha}

    Energy Technology Data Exchange (ETDEWEB)

    Perlstein, R.S.; Mehta, N.R.; Neta, R.; Whitnall, M.H. [Armed Forces Radiobiology Research Institute, Bethesda, MD (United States); Mougey, E.H. [Walter Reed Army Institute of Research, Washington, DC (United States)

    1995-03-01

    Recombinant human interleukin-1{alpha} (rhIL-1{alpha}) has significant potential as a radioprotector and/or treatment for radiation-induced hematopoietic injury. Both IL-1 and whole-body ionizing irradiation acutely stimulate the hypothalamic-pituitary-adrenal axis. We therefore assessed the interaction of whole-body irradiation and rhIL-1{alpha} in altering the functioning of the axis in mice. Specifically, we determined the adrenocorticotropin (ACTH) and corticosterone responses to rhIL-1{alpha} administered just before and hours to days after whole-body or sham irradiation. Our results indicate that whole-body irradiation does not potentiate the rhIL-1{alpha}-induced increase in ACTH levels at the doses used. In fact, the rhIL-1{alpha}-induced increase in plasma ACTH is transiently impaired when the cytokine is administered 5 h after, but not 1 h before, exposure to whole-body irradiation. The ACTH response may be inhibited by elevated corticosterone levels after whole-body irradiation, or by other radiation-induced effects on the pituitary gland and hypothalamus. 36 refs., 3 figs.

  12. Virulent Type A Francisella tularensis actively suppresses cytokine responses in human monocytes

    Science.gov (United States)

    Gillette, Devyn D.; Curry, Heather M.; Cremer, Thomas; Ravneberg, David; Fatehchand, Kavin; Shah, Prexy A.; Wewers, Mark D.; Schlesinger, Larry S.; Butchar, Jonathan P.; Tridandapani, Susheela; Gavrilin, Mikhail A.

    2014-01-01

    Background: Human monocyte inflammatory responses differ between virulent and attenuated Francisella infection. Results: A mixed infection model showed that the virulent F. tularensis Schu S4 can attenuate inflammatory cytokine responses to the less virulent F. novicida in human monocytes. Conclusion: F. tularensis dampens inflammatory response by an active process. Significance: This suppression may contribute to enhanced pathogenicity of F. tularensis. Francisella tularensis is a Gram-negative facultative bacterium that can cause the disease tularemia, even upon exposure to low numbers of bacteria. One critical characteristic of Francisella is its ability to dampen or subvert the host immune response. Previous work has shown that monocytes infected with highly virulent F. tularensis subsp. tularensis strain Schu S4 responded with a general pattern of quantitatively reduced pro-inflammatory signaling pathway genes and cytokine production in comparison to those infected with the less virulent related F. novicida. However, it has been unclear whether the virulent Schu S4 was merely evading or actively suppressing monocyte responses. By using mixed infection assays with F. tularensis and F. novicida, we show that F. tularensis actively suppresses monocyte pro-inflammatory responses. Additional experiments show that this suppression occurs in a dose-dependent manner and is dependent upon the viability of F. tularensis. Importantly, F. tularensis was able to suppress pro-inflammatory responses to earlier infections with F. novicida. These results lend support that F. tularensis actively dampens human monocyte responses and this likely contributes to its enhanced pathogenicity. PMID:24783062

  13. Antigen-Specific Interferon-Gamma Responses and Innate Cytokine Balance in TB-IRIS

    Science.gov (United States)

    Goovaerts, Odin; Jennes, Wim; Massinga-Loembé, Marguerite; Ceulemans, Ann; Worodria, William; Mayanja-Kizza, Harriet; Colebunders, Robert; Kestens, Luc

    2014-01-01

    Background Tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) remains a poorly understood complication in HIV-TB patients receiving antiretroviral therapy (ART). TB-IRIS could be associated with an exaggerated immune response to TB-antigens. We compared the recovery of IFNγ responses to recall and TB-antigens and explored in vitro innate cytokine production in TB-IRIS patients. Methods In a prospective cohort study of HIV-TB co-infected patients treated for TB before ART initiation, we compared 18 patients who developed TB-IRIS with 18 non-IRIS controls matched for age, sex and CD4 count. We analyzed IFNγ ELISpot responses to CMV, influenza, TB and LPS before ART and during TB-IRIS. CMV and LPS stimulated ELISpot supernatants were subsequently evaluated for production of IL-12p70, IL-6, TNFα and IL-10 by Luminex. Results Before ART, all responses were similar between TB-IRIS patients and non-IRIS controls. During TB-IRIS, IFNγ responses to TB and influenza antigens were comparable between TB-IRIS patients and non-IRIS controls, but responses to CMV and LPS remained significantly lower in TB-IRIS patients. Production of innate cytokines was similar between TB-IRIS patients and non-IRIS controls. However, upon LPS stimulation, IL-6/IL-10 and TNFα/IL-10 ratios were increased in TB-IRIS patients compared to non-IRIS controls. Conclusion TB-IRIS patients did not display excessive IFNγ responses to TB-antigens. In contrast, the reconstitution of CMV and LPS responses was delayed in the TB-IRIS group. For LPS, this was linked with a pro-inflammatory shift in the innate cytokine balance. These data are in support of a prominent role of the innate immune system in TB-IRIS. PMID:25415590

  14. Cytokine Responses to Acute Exercise in Healthy Older Adults: The Effect of Cardiorespiratory Fitness

    Directory of Open Access Journals (Sweden)

    Mark T. Windsor

    2018-03-01

    Full Text Available Markers of chronic inflammation increase with aging, and are associated with cardiovascular disease prevalence and mortality. Increases in fitness with exercise training have been associated with lower circulating concentrations of cytokines known to have pro-inflammatory actions (such as interleukin-6 [IL-6] and higher circulating concentrations of anti-inflammatory cytokines (interleukin-10 [IL-10]. However, the effect of cardiorespiratory fitness on acute cytokine responses to a single bout of exercise in healthy older individuals is unknown. We compared the response of plasma cytokines IL-6, tumor necrosis factor-alpha (TNF-α and IL-10 to a bout of moderate-intensity continuous and higher-intensity interval exercise between older individuals with higher and lower levels of cardiorespiratory fitness. Sixteen lower-fit (VO2peak: 22.6±2.8 mL.kg−1.min−1 and fourteen higher-fit participants (VO2peak: 37.4±5.9 mL.kg−1.min−1 completed three 24 min experimental protocols in a randomized order: (1 moderate-intensity continuous exercise (40% of peak power output [PPO]; (2 higher-intensity interval exercise (12 × 1 min intervals at 70% PPO separated by 1 min periods at 10% PPO; or (3 non-exercise control. Plasma cytokines were measured at rest, immediately after, and during 90 min of recovery following exercise or control. Plasma IL-6 concentrations at baseline were greater in the higher-fit compared to the lower-fit group (P = 0.02, with no difference in plasma IL-10 or TNF-α concentrations at baseline between groups. Plasma IL-6 and IL-10 concentrations in both groups increased immediately after all protocols (IL-6: P = 0.02, IL-10: P < 0.01. However, there was no difference in the IL-6 and IL-10 response between the exercise and non-exercise (control protocols. After all protocols, no changes in plasma TNF-α concentrations were observed in either the higher- or lower-fit groups. In this study, basal concentrations of circulating IL-6

  15. Transient response of level instruments in a research reactor

    International Nuclear Information System (INIS)

    Cheng, Lap Y.

    1989-01-01

    A numerical model has been developed to simulate the dynamics of water level instruments in a research nuclear reactor. A bubble device, with helium gas as the working fluid, is used to monitor liquid level by sensing the static head pressure due to the height of liquid in the reactor vessel. A finite-difference model is constructed to study the transient response of the water level instruments to pressure perturbations. The field equations which describe the hydraulics of the helium gas in the bubbler device are arranged in the form of a tridiagonal matrix and the field variables are solved at each time step by the Thomas algorithm. Simulation results indicate that the dynamic response of the helium gas depends mainly on the volume and the inertia of the gas in the level instrument tubings. The anomalies in the simulated level indication are attributed to the inherent lag in the level instrument due to the hydraulics of the system. 1 ref., 5 figs

  16. Transient lower esophageal sphincter relaxation and esophageal motor response.

    Science.gov (United States)

    Schneider, Joachim H; Küper, Markus A; Königsrainer, Alfred; Brücher, Björn L D M

    2010-04-01

    Gastroesophageal reflux is caused by transient lower esophageal sphincter relaxations (TLESRs) in healthy individuals and in most patients with gastroesophageal reflux disease (GERD). Refluxate is normally propelled by pharyngeally induced swallowing events, but TLESRs may also be accompanied by retrograde esophageal motor responses (EMRs). These contractions have not previously been investigated and their effect on esophageal clearance is not known. The aim of this study was to assess the frequency of EMRs after TLESR in healthy individuals and GERD patients and to develop an animal model for further investigation of EMRs. The frequency of TLESRs and esophageal body contractions after TLESRs was assessed using ambulatory manometry in five healthy individuals and five GERD patients. An animal model was developed for reproducible provocation of TLESRs and subsequent EMRs. Patients with GERD have significantly more TLESRs than healthy individuals. However, post-TLESR EMRs were not more frequent in the GERD group. All post-TLESR EMRs presented as simultaneous contractions of the esophagus. The feline model allowed reproducible initiation of the esophageal motor response after TLESR, showing that EMRs can be induced by external mechanoreceptor stimulation simultaneously with LES relaxation. This experimental design imitates the conditions after fundoplication in humans. The study demonstrated that GERD patients have significantly more TLESRs in comparison with healthy individuals, but these were only incidental to EMRs. Further research is needed to improve our understanding of esophageal motility disorders. The animal model presented offers a feasible tool for investigating TLESR-induced esophageal motility.

  17. Correlation of cutaneous sensitivity and cytokine response in children with asthma

    Directory of Open Access Journals (Sweden)

    Meenu Singh

    2017-01-01

    Full Text Available Background: Food allergy occurs in a significant portion of pediatric asthma. Various cells and their mediators/cytokines play a pivotal role in orchestrating the airway inflammatory response in asthma. Objective: To study the cutaneous hypersensitivity, Th1, Th2, and Th17 response of pediatric population with asthma and genetic predisposition to atopy, by determining total immunoglobulin E (IgE level in response to various food allergens. Materials and Methods: Fifty asthmatic children with a history of worsening symptoms by various food allergens (study group and twenty healthy children (control group were included. Food allergy was assessed through skin prick test (SPT of various food allergens. Total serum IgE level was measured by sandwich ELISA, and T-cell (Th1, Th2, and Th17-dependent cytokines were measured by flow cytometry. Results: All 50 asthmatic children in the study group showed SPT positivity against various food allergens (rice = 17; banana, fish and groundnut = 10; wheat = 9; milk and orange = 7; egg = 6; and mango = 4. The average total IgE level in the study group was 316.8 ± 189.8 IU/mL. A significant positive correlation of total IgE with interleukin 17 (IL-17 (r = 0.796; P < 0.0001, IL-13 (r = 0.383; P = 0.01, and IL-4 (r = 0.263; P = 0.043 level was noted. A significant negative correlation of total IgE was noted with interferon gamma (r = −0.5823; P < 0.0001 and IL-10 (r = −0.4474; P < 0.001 level and the duration of breastfeeding (r = −0.31, P = 0.03. Conclusions: The present study found a positive correlation between total serum IgE level and Th2, Th17 cytokines in a pediatric population with asthma. A significant negative correlation was found between the duration of breastfeeding and the cytokines.

  18. Involvement of three mechanisms in the alteration of cytokine responses by sodium methyldithiocarbamate

    International Nuclear Information System (INIS)

    Pruett, Stephen B.; Fan, Ruping; Zheng, Qiang

    2006-01-01

    Sodium methyldithiocarbamate (SMD) is the third most abundantly used conventional pesticide in the U.S. We recently reported that it alters the induction of cytokine production mediated though Toll-like receptor (TLR) 4 at relevant dosages in mice. Its chemical properties and evidence from the literature suggest thee potential mechanisms of action for this compound. It could either act as a free radical scavenger (by means of its free S - group) or promote oxidation by breaking down to form methylisothiocyanate, which can deplete glutathione. It is a potent copper chelator and may affect the availability of copper to a number of copper-dependent enzymes (including some signaling molecules). SMD induces a classical neuroendocrine stress response characterized by elevated serum corticosterone concentrations, which could affect cytokine production. Although each of these mechanisms could potentially contribute to altered cytokine responses, direct evidence is lacking. The present study was conducted to obtain such evidence. The role of redox balance was investigated by pretreating mice with N-acetyl cysteine (NAC), which increases cellular glutathione concentrations, before administration of SMD. NAC exacerbated the SMD-induced suppression of IL-12 and the SMD-induced enhancement of IL-10 in the serum. The role of copper chelation was investigated by comparing the effects of SMD with an equimolar dose to SMD that was administered in the form of a copper chelation complex. Addition of copper significantly decreased the action of SMD on IL-12 production but not on IL-10 production. The role of the stress response was investigated by pretreating mice with antagonists of corticosterone and catecholamines. This treatment partially prevented the action of SMD on IL-10 and IL-12 in the peritoneal fluid. The results suggest that all of the proposed mechanisms have some role in the alteration of cytokine production by SMD

  19. Th9 cytokines response and its possible implications in the immunopathogenesis of leprosy.

    Science.gov (United States)

    de Sousa, Jorge Rodrigues; Pagliari, Carla; de Almeida, Dandara Simone Maia; Barros, Luiz Fernando Lima; Carneiro, Francisca Regina Oliveira; Dias, Leonidas Braga; de Souza Aarão, Tinara Leila; Quaresma, Juarez Antonio Simões

    2017-06-01

    Leprosy is an infectious-contagious disease whose clinical evolution depends on the interaction of the infectious agent with the immune response of the host, leading to a clinical spectrum that ranges from lepromatous leprosy (susceptibility, LL) to tuberculoid leprosy (resistance, TT). The immune response profile will depend on the pattern of cytokine production and on the activity of macrophages during infection. Classically, the clinical evolution of leprosy has been associated with Th1/Th2 cytokine profiles, but the role of new cytokine profiles such as T helper 9 (Th9) remains to be elucidated. To evaluate the tissue expression profile of these cytokines, a cross-sectional study was conducted using a sample of 30 leprosy skin lesion biopsies obtained from patients with leprosy, 16 TT and 14 lepromatous LL. Immunohistochemical analysis revealed a significant difference in interleukin (IL)-9, IL-4 transforming growth factor (TGF)-β and IL-10 levels between the two groups. IL-9 was more expressed in TT lesions compared with LL lesions. Higher expression of IL-4, IL-10 and TGF-β was observed in LL compared with TT. IL-4, IL-10 and TGF-β tended to be negatively correlated with the expression of IL-9, indicating a possible antagonistic activity in tissue. The results suggest that Th9 lymphocytes may be involved in the response to Mycobacterium leprae , positively or negatively regulating microbicidal activity of the local immune system in the disease. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  20. Cytokine, antibody and proliferative cellular responses elicited by Taenia solium calreticulin upon experimental infection in hamsters.

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    Fela Mendlovic

    Full Text Available Taenia solium causes two diseases in humans, cysticercosis and taeniosis. Tapeworm carriers are the main risk factor for neurocysticercosis. Limited information is available about the immune response elicited by the adult parasite, particularly the induction of Th2 responses, frequently associated to helminth infections. Calreticulin is a ubiquitous, multifunctional protein involved in cellular calcium homeostasis, which has been suggested to play a role in the regulation of immune responses. In this work, we assessed the effect of recombinant T. solium calreticulin (rTsCRT on the cytokine, humoral and cellular responses upon experimental infection in Syrian Golden hamsters (Mesocricetus auratus. Animals were infected with T. solium cysticerci and euthanized at different times after infection. Specific serum antibodies, proliferative responses in mesenteric lymph nodes and spleen cells, as well as cytokines messenger RNA (mRNA were analyzed. The results showed that one third of the infected animals elicited anti-rTsCRT IgG antibodies. Interestingly, mesenteric lymph node (MLN cells from either infected or non-infected animals did not proliferate upon in vitro stimulation with rTsCRT. Additionally, stimulation with a tapeworm crude extract resulted in increased expression of IL-4 and IL-5 mRNA. Upon stimulation, rTsCRT increased the expression levels of IL-10 in spleen and MLN cells from uninfected and infected hamsters. The results showed that rTsCRT favors a Th2-biased immune response characterized by the induction of IL-10 in mucosal and systemic lymphoid organs. Here we provide the first data on the cytokine, antibody and cellular responses to rTsCRT upon in vitro stimulation during taeniasis.

  1. High Sensitivity of Aged Mice to Deoxynivalenol (Vomitoxin)-Induced Anorexia Corresponds to Elevated Proinflammatory Cytokine and Satiety Hormone Responses.

    Science.gov (United States)

    Clark, Erica S; Flannery, Brenna M; Gardner, Elizabeth M; Pestka, James J

    2015-10-19

    Deoxynivalenol (DON), a trichothecene mycotoxin that commonly contaminates cereal grains, is a public health concern because of its adverse effects on the gastrointestinal and immune systems. The objective of this study was to compare effects of DON on anorectic responses in aged (22 mos) and adult (3 mos) mice. Aged mice showed increased feed refusal with both acute i.p. (1 mg/kg and 5 mg/kg) and dietary (1, 2.5, 10 ppm) DON exposure in comparison to adult mice. In addition to greater suppression of food intake from dietary DON exposure, aged mice also exhibited greater but transient body weight suppression. When aged mice were acutely exposed to 1 mg/kg bw DON i.p., aged mice displayed elevated DON and DON3GlcA tissue levels and delayed clearance in comparison with adult mice. Acute DON exposure also elicited higher proinflammatory cytokine and satiety hormone responses in the plasma of the aged group compared with the adult group. Increased susceptibility to DON-induced anorexia in aged mice relative to adult mice suggests that advanced life stage could be a critical component in accurate human risk assessments for DON and other trichothecenes.

  2. High Sensitivity of Aged Mice to Deoxynivalenol (Vomitoxin-Induced Anorexia Corresponds to Elevated Proinflammatory Cytokine and Satiety Hormone Responses

    Directory of Open Access Journals (Sweden)

    Erica S. Clark

    2015-10-01

    Full Text Available Deoxynivalenol (DON, a trichothecene mycotoxin that commonly contaminates cereal grains, is a public health concern because of its adverse effects on the gastrointestinal and immune systems. The objective of this study was to compare effects of DON on anorectic responses in aged (22 mos and adult (3 mos mice. Aged mice showed increased feed refusal with both acute i.p. (1 mg/kg and 5 mg/kg and dietary (1, 2.5, 10 ppm DON exposure in comparison to adult mice. In addition to greater suppression of food intake from dietary DON exposure, aged mice also exhibited greater but transient body weight suppression. When aged mice were acutely exposed to 1 mg/kg bw DON i.p., aged mice displayed elevated DON and DON3GlcA tissue levels and delayed clearance in comparison with adult mice. Acute DON exposure also elicited higher proinflammatory cytokine and satiety hormone responses in the plasma of the aged group compared with the adult group. Increased susceptibility to DON-induced anorexia in aged mice relative to adult mice suggests that advanced life stage could be a critical component in accurate human risk assessments for DON and other trichothecenes.

  3. Influence of HMB supplementation and resistance training on cytokine responses to resistance exercise.

    Science.gov (United States)

    Kraemer, William J; Hatfield, Disa L; Comstock, Brett A; Fragala, Maren S; Davitt, Patrick M; Cortis, Cristina; Wilson, Jacob M; Lee, Elaine C; Newton, Robert U; Dunn-Lewis, Courtenay; Häkkinen, Keijo; Szivak, Tunde K; Hooper, David R; Flanagan, Shawn D; Looney, David P; White, Mark T; Volek, Jeff S; Maresh, Carl M

    2014-01-01

    The purpose of this study was to determine the effects of a multinutritional supplement including amino acids, β-hydroxy-β-methylbutyrate (HMB), and carbohydrates on cytokine responses to resistance exercise and training. Seventeen healthy, college-aged men were randomly assigned to a Muscle Armor™ (MA; Abbott Nutrition, Columbus, OH) or placebo supplement group and 12 weeks of resistance training. An acute resistance exercise protocol was administered at 0, 6, and 12 weeks of training. Venous blood samples at pre-, immediately post-, and 30-minutes postexercise were analyzed via bead multiplex immunoassay for 17 cytokines. After 12 weeks of training, the MA group exhibited decreased interferon-gamma (IFN-γ) and interleukin (IL)-10. IL-1β differed by group at various times. Granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-6, IL-7, IL-8, IL-12p70, IL-13, IL-17, monocyte chemoattractant protein-1 (MCP-1), and macrophage inflammatory protein-1 beta (MIP-1β) changed over the 12-week training period but did not differ by group. Twelve weeks of resistance training alters the cytokine response to acute resistance exercise, and supplementation with HMB and amino acids appears to further augment this result.

  4. Oxidative stress modulates the cytokine response of differentiated Th17 and Th1 cells.

    Science.gov (United States)

    Abimannan, Thiruvaimozhi; Peroumal, Doureradjou; Parida, Jyoti R; Barik, Prakash K; Padhan, Prasanta; Devadas, Satish

    2016-10-01

    Reactive oxygen species (ROS) signaling is critical in T helper (Th) cell differentiation; however its role in differentiated Th cell functions is unclear. In this study, we investigated the role of oxidative stress on the effector functions of in vitro differentiated mouse Th17 and Th1 cells or CD4 + T cells from patients with Rheumatoid Arthritis using pro-oxidants plumbagin (PB) and hydrogen peroxide. We found that in mouse Th cells, non-toxic concentration of pro-oxidants inhibited reactivation induced expression of IL-17A in Th17 and IFN-γ in Th1 cells by reducing the expression of their respective TFs, RORγt and T-bet. Interestingly, in both the subsets, PB increased the expression of IL-4 by enhancing reactivation induced ERK1/2 phosphorylation. We further investigated the cytokine modulatory effect of PB on CD4 + T cells isolated from PBMCs of patients with Rheumatoid Arthritis, a well-known Th17 and or Th1 mediated disease. In human CD4 + T cells from Rheumatoid Arthritis patients, PB reduced the frequencies of IL-17A + (Th17), IFN - γ + (Th1) and IL-17A + /IFN - γ + (Th17/1) cells and also inhibited the production of pro-inflammatory cytokines TNF-α and IL-6. N-Acetyl Cysteine (NAC) an antioxidant completely reversed PB mediated cytokine modulatory effects in both mouse and human cells indicating a direct role for ROS. Together our data suggest that oxidative microenvironment can alter cytokine response of terminally differentiated cells and thus altering intracellular ROS could be a potential way to target Th17 and Th1 cells in autoimmune disorders. Copyright © 2016. Published by Elsevier Inc.

  5. Inflammatory cytokines and plasma redox status responses in hypertensive subjects after heat exposure

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    S.F. Fonseca

    2016-03-01

    Full Text Available Hypertension is characterized by a pro-inflammatory status, including redox imbalance and increased levels of pro-inflammatory cytokines, which may be exacerbated after heat exposure. However, the effects of heat exposure, specifically in individuals with inflammatory chronic diseases such as hypertension, are complex and not well understood. This study compared the effects of heat exposure on plasma cytokine levels and redox status parameters in 8 hypertensive (H and 8 normotensive (N subjects (age: 46.5±1.3 and 45.6±1.4 years old, body mass index: 25.8±0.8 and 25.6±0.6 kg/m2, mean arterial pressure: 98.0±2.8 and 86.0±2.3 mmHg, respectively. They remained at rest in a sitting position for 10 min in a thermoneutral environment (22°C followed by 30 min in a heated environmental chamber (38°C and 60% relative humidity. Blood samples were collected before and after heat exposure. Plasma cytokine levels were measured using sandwich ELISA kits. Plasma redox status was determined by thiobarbituric acid reactive substances (TBARS levels and ferric reducing ability of plasma (FRAP. Hypertensive subjects showed higher plasma levels of IL-10 at baseline (P<0.05, although levels of this cytokine were similar between groups after heat exposure. Moreover, after heat exposure, hypertensive individuals showed higher plasma levels of soluble TNF receptor (sTNFR1 and lower TBARS (P<0.01 and FRAP (P<0.05 levels. Controlled hypertensive subjects, who use angiotensin-converting-enzyme inhibitor (ACE inhibitors, present an anti-inflammatory status and balanced redox status. Nevertheless, exposure to a heat stress condition seems to cause an imbalance in the redox status and an unregulated inflammatory response.

  6. DNA methylation differentially regulates cytokine secretion in gingival epithelia in response to bacterial challenges.

    Science.gov (United States)

    Drury, Jeanie L; Chung, Whasun Oh

    2015-03-01

    Epigenetic modifications are changes in gene expression without altering DNA sequence. We previously reported that bacteria-specific innate immune responses are regulated by epigenetic modifications. Our hypothesis is that DNA methylation affects gingival cytokine secretion in response to bacterial stimulation. Gingival epithelial cells (GECs) were treated with DNMT-1 inhibitors prior to Porphyromonas gingivalis (Pg) or Fusobacterium nucleatum (Fn) exposure. Protein secretion was assessed using ELISA. Gene expression was quantified using qRT-PCR. The ability of bacteria to invade inhibitor pretreated GECs was assessed utilizing flow cytometry. Changes were compared to unstimulated GECs. GEC upregulation of IL-6 and CXCL1 by Pg or Fn stimulation was significantly diminished by inhibitor pretreatment. Pg stimulated IL-1α secretion and inhibitor pretreatment significantly enhanced this upregulation, while Fn alone or with inhibitor pretreatment had no effect on IL-1α expression. GEC upregulation of human beta-definsin-2 in response to Pg and Fn exposure was enhanced following the inhibitor pretreatment. GEC susceptibility to bacterial invasion was unaltered. These results suggest that DNA methylation differentially affects gingival cytokine secretion in response to Pg or Fn. Our data provide basis for better understanding of how epigenetic modifications, brought on by exposure to oral bacteria, will subsequently affect host susceptibility to oral diseases. © FEMS 2014. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  7. The role of multiple negative social relationships in inflammatory cytokine responses to a laboratory stressor

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    Sunmi Song

    2015-06-01

    Full Text Available The present study examined the unique impact of perceived negativity in multiple social relationships on endocrine and inflammatory responses to a laboratory stressor. Via hierarchical cluster analysis, those who reported negative social exchanges across relationships with a romantic partner, family, and their closest friend had higher mean IL-6 across time and a greater increase in TNF-α from 15 min to 75 min post stress. Those who reported negative social exchanges across relationships with roommates, family, and their closest friend showed greater IL-6 responses to stress. Differences in mean IL-6 were accounted for by either depressed mood or hostility, whereas differences in the cytokine stress responses remained significant after controlling for those factors. Overall, this research provides preliminary evidence to suggest that having multiple negative relationships may exacerbate acute inflammatory responses to a laboratory stressor independent of hostility and depressed mood.

  8. The role of multiple negative social relationships in inflammatory cytokine responses to a laboratory stressor.

    Science.gov (United States)

    Song, Sunmi; Graham-Engeland, Jennifer E; Corwin, Elizabeth J; Ceballos, Rachel M; Taylor, Shelley E; Seeman, Teresa; Klein, Laura Cousino

    2015-01-01

    The present study examined the unique impact of perceived negativity in multiple social relationships on endocrine and inflammatory responses to a laboratory stressor. Via hierarchical cluster analysis, those who reported negative social exchanges across relationships with a romantic partner, family, and their closest friend had higher mean IL-6 across time and a greater increase in TNF-α from 15 min to 75 min post stress. Those who reported negative social exchanges across relationships with roommates, family, and their closest friend showed greater IL-6 responses to stress. Differences in mean IL-6 were accounted for by either depressed mood or hostility, whereas differences in the cytokine stress responses remained significant after controlling for those factors. Overall, this research provides preliminary evidence to suggest that having multiple negative relationships may exacerbate acute inflammatory responses to a laboratory stressor independent of hostility and depressed mood.

  9. Heroin use is associated with suppressed pro-inflammatory cytokine response after LPS exposure in HIV-infected individuals.

    Directory of Open Access Journals (Sweden)

    Hinta Meijerink

    Full Text Available Opioid use is associated with increased incidence of infectious diseases. Although experimental studies have shown that opioids affect various functions of immune cells, only limited data are available from human studies. Drug use is an important risk factor for HIV transmission; however no data are available whether heroin and/or methadone modulate immune response. Therefore, we examined the effect of heroin and methadone use among HIV-infected individuals on the production of cytokines after ex vivo stimulation with various pathogens.Treatment naïve HIV-infected individuals from Indonesia were recruited. Several cohorts of individuals were recruited: 1 using heroin 2 receiving methadone opioid substitution 3 using heroin over 1 year ago and 4 controls (never used opioids. Whole blood was stimulated with Mycobacterium tuberculosis, Candida albicans and LPS for 24 to 48 hours. Cytokine production (IL-1 β, IL-6, IL-10, IFN-α, IFN-γ and TNF-α was determined using multiplex beads assay.Among 82 individuals, the cytokine levels in unstimulated samples did not differ between groups. Overall, heroin users had significantly lower cytokine response after exposure to LPS (p<0.05. After stimulation with either M. tuberculosis or C. albicans the cytokine production of all groups were comparable.The cytokine production after exposure to LPS is significantly down-regulated in HIV-infected heroin users. Interesting, methadone use did not suppress cytokine response, which could have implications guidelines of opioid substitution.

  10. Transient river response, captured by channel steepness and its concavity

    Science.gov (United States)

    Vanacker, Veerle; von Blanckenburg, Friedhelm; Govers, Gerard; Molina, Armando; Campforts, Benjamin; Kubik, Peter W.

    2015-01-01

    Mountain rivers draining tropical regions are known to be great conveyor belts carrying efficiently more than half of the global sediment flux to the oceans. Many tropical mountain areas are located in tectonically active belts where the hillslope and stream channel morphology are rapidly evolving in response to changes in base level. Here, we report basin-wide denudation rates for an east-west transect through the tropical Andes. Hillslope and channel morphology vary systematically from east to west, reflecting the transition from high relief, strongly dissected topography in the escarpment zones into relatively low relief topography in the inter-Andean valley. The spatial pattern of differential denudation rates reflects the transient adjustment of the landscape to rapid river incision following tectonic uplift and river diversion. In the inter-Andean valley, upstream of the wave of incision, slopes and river channels display a relatively smooth, concave-up morphology and denudation rates (time scale of 104-105 a) are consistently low (3 to 200 mm/ka). In contrast, slopes and river channels of rejuvenated basins draining the eastern cordillera are steep to very steep; and the studied drainage basins show a wide range of denudation rate values (60 to 400 mm/ka) that increase systematically with increasing basin mean slope gradient, channel steepness, and channel convexity. Drainage basins that are characterised by strong convexities in their river longitudinal profiles systematically have higher denudation rates. As such, this is one of the first studies that provides field-based evidence of a correlation between channel concavity and basin mean denudation rates, consistent with process-based fluvial incision models.

  11. Differential effect of conditioning regimens on cytokine responses during allogeneic stem cell transplantation

    DEFF Research Database (Denmark)

    Andersen, J; Heilmann, C; Jacobsen, N

    2006-01-01

    The purpose of this study was to characterize cytokine responses during conditioning in patients undergoing allogeneic stem cell transplantation (SCT) with the aim to identify which markers that may reliably reflect inflammatory activity during conditioning. We investigated inflammatory and anti.......002), followed by VP-16 (184%, P=0.03), cyclophosphamide (129%, P=0.03) and total body irradiation (148%, P=0.0005). Administration of i.v. busulfan (Busilvex; BU) was not associated with significant changes in sTNFRI levels. At day 0 (the day of stem cell infusion) the sTNFRI levels were not only elevated...

  12. Nasal Lipopolysaccharide Challenge and Cytokine Measurement Reflects Innate Mucosal Immune Responsiveness.

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    Jaideep Dhariwal

    Full Text Available Practical methods of monitoring innate immune mucosal responsiveness are lacking. Lipopolysaccharide (LPS is a component of the cell wall of Gram negative bacteria and a potent activator of Toll-like receptor (TLR-4. To measure LPS responsiveness of the nasal mucosa, we administered LPS as a nasal spray and quantified chemokine and cytokine levels in mucosal lining fluid (MLF.We performed a 5-way cross-over, single blind, placebo-controlled study in 15 healthy non-atopic subjects (n = 14 per protocol. Doses of ultrapure LPS (1, 10, 30 or 100μg/100μl or placebo were administered by a single nasal spray to each nostril. Using the recently developed method of nasosorption with synthetic adsorptive matrices (SAM, a series of samples were taken. A panel of seven cytokines/chemokines were measured by multiplex immunoassay in MLF. mRNA for intercellular cell adhesion molecule-1 (ICAM-1 was quantified from nasal epithelial curettage samples taken before and after challenge.Topical nasal LPS was well tolerated, causing no symptoms and no visible changes to the nasal mucosa. LPS induced dose-related increases in MLF levels of IL-1β, IL-6, CXCL8 (IL-8 and CCL3 (MIP-1α (AUC at 0.5 to 10h, compared to placebo, p<0.05 at 30 and 100μg LPS. At 100μg LPS, IL-10, IFN-α and TNF-α were also increased (p<0.05. Dose-related changes in mucosal ICAM-1 mRNA were also seen after challenge, and neutrophils appeared to peak in MLF at 8h. However, 2 subjects with high baseline cytokine levels showed prominent cytokine and chemokine responses to relatively low LPS doses (10μg and 30μg LPS.Topical nasal LPS causes dose-dependent increases in cytokines, chemokines, mRNA and cells. However, responsiveness can show unpredictable variations, possibly because baseline innate tone is affected by environmental factors. We believe that this new technique will have wide application in the study of the innate immune responses of the respiratory mucosa.Ultrapure LPS was used

  13. Aeromonas caviae strain induces Th1 cytokine response in mouse intestinal tract

    Energy Technology Data Exchange (ETDEWEB)

    Hayes, S L; Lye, D J; McKinstry, Craig A.; Vesper, Sephen J.

    2010-01-01

    Aeromonas caviae has been associated with human gastrointestinal disease. Strains of this species typically lack virulence factors (VFs) such as enterotoxins and hemolysins that are produced by other human pathogens of the Aeromonas genus. Microarray profiling of murine small intestinal extracts, 24 hours after oral infection with an A. caviae strain, provides evidence of a Th1 type immune response. A large number of gamma-interferon (γ-IFN) induced genes are up-regulated as well as several tumor necrosis factor-alpha (TNF-α) transcripts. A. caviae has always been considered as opportunistic pathogen because it lacks obvious virulence factors. This current effort suggests that an A. caviae strain can colonize the murine intestinal tract and cause what has been described by others as a dysregulatory cytokine response. This response could explain why a number of diarrheal waterborne disease cases have been attributed to A. caviae even though it lacks obvious enteropathogenic properties.

  14. Salivary cytokine response in the aftermath of stress: An emotion regulation perspective.

    Science.gov (United States)

    Newton, Tamara L; Fernandez-Botran, Rafael; Lyle, Keith B; Szabo, Yvette Z; Miller, James J; Warnecke, Ashlee J

    2017-09-01

    Elevated inflammation in the context of stress has been implicated in mental and physical health. Approaching this from an emotion regulation perspective, we tested whether the salivary cytokine response to stress is dampened by using distraction to minimize opportunity for poststressor rumination. Healthy young adults were randomized to an acute stressor: modified Trier Social Stress Test (TSST, Study 1) or angry memory retrieval (Study 2). Within each study, participants were randomized to poststressor condition-rest or distraction-at a 3:1 ratio. Saliva, collected before and 40 min after the end of each stressor, was assayed for proinflammatory cytokines (PICs): interleukin-1β (IL-1β), TNF-α, and IL-6. Both stressors increased all PICs, and both provoked negative emotion. At 40 min post-TSST, salivary PIC increases did not differ between distraction and rest, but correlated positively with emotional reactivity to stress. At 40 min after memory retrieval, IL-1β increases and intrusive rumination were lower during distraction than rest, but did not correlate with emotional reactivity. Trait rumination and interference control mechanisms, also measured, played little role in PIC increases. Overall, after some stressors, some salivary cytokine responses are lower during distraction than rest. The roles of specific emotions, emotional intensity, and poststressor timing of saliva collection in this finding require clarification. Furthermore, the possibility of two affective paths to inflammation in the context of stress-one sensitive to opportunities for early occurring emotion regulation (as reflected in emotional reactivity), and one sensitive to late-occurring emotion regulation (as reflected in distraction after stress)-deserves attention. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  15. Porcine blood mononuclear cell cytokine responses to PAMP molecules: comparison of mRNA and protein production

    DEFF Research Database (Denmark)

    Sørensen, Nanna Skall; Skovgaard, Kerstin; Heegaard, Peter M. H.

    2011-01-01

    Pathogen-associated molecular patterns (PAMPs) are conserved molecules of microorganisms inducing innate immune cells to secrete distinct patterns of cytokines. In veterinary species, due to a lack of specific antibodies, cytokines are often monitored as expressed mRNA only. This study investigated...... the induction of IFN-α, IL-12 p40, IL-1β, TNF-α, IL-6 and IL-10 by PAMP-molecules [CpG oligonucleotide D19 (CpG), peptidoglycan (PGN), lipopolysaccharide (LPS), Pam3Cys and poly-U] in porcine blood mononuclear cells (BMC) within a 24h period. As expected, cytokine responses were PAMP-specific, CpG inducing IFN...

  16. Improving the transient response of a bolt-clamped Langevin transducer using a parallel resistor.

    Science.gov (United States)

    Chang, Kuo Tsi

    2003-08-01

    This paper suggests a parallel resistor to reduce DC time constant and DC response time of the transient response, induced immediately after an AC voltage connected to a bolt-clamped Langevin transducer (BLT) is switched off. An equivalent circuit is first expressed. Then, an open-circuit transient response at the terminals induced by initial states is derived and measured, and thus parameters for losses of the BLT device are estimated by DC and AC time constants of the transient response. Moreover, a driving and measuring system is designed to determine transient response and steady-state responses of the BLT device, and a parallel resistor is connected to the BLT device to reduce the DC time constant. Experimental results indicate that the DC time constant greatly exceeds the AC time constant without the parallel resistor, and greatly decreases from 42 to 1 ms by a 100-kOmega parallel resistor.

  17. Inherited Variation in Cytokine, Acute Phase Response, and Calcium Metabolism Genes Affects Susceptibility to Infective Endocarditis

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    Anastasia V. Ponasenko

    2017-01-01

    Full Text Available Infective endocarditis (IE is a septic inflammation of the endocardium. Recognition of microbial patterns, cytokine and acute phase responses, hemostasis features, and alterations in plasma lipid and calcium profile all have been reported to affect pathogenesis and clinical course of IE. Having recruited 123 patients with IE and 300 age-, sex-, and ethnicity-matched healthy blood donors, we profiled their genomic DNA for 35 functionally significant polymorphisms within the 22 selected genes involved in the abovementioned pathways, with the further genetic association analysis. We found that the G/A genotype of the rs1143634 polymorphism within the IL1B gene, the G/T genotype of the rs3212227 polymorphism within the IL12B gene, the A/G genotype of the rs1130864 polymorphism within the CRP gene, and the G allele of the rs1801197 polymorphism within the CALCR gene were associated with a decreased risk of IE whereas the T/T genotype of the rs1205 polymorphism within the CRP gene was associated with a higher risk of IE. Furthermore, heterozygous genotypes of the rs1143634 and rs3212227 polymorphisms were associated with the higher plasma levels of IL-1β and IL-12, respectively. Our results indicate that inherited variation in the cytokine, acute phase response, and calcium metabolism pathways may be linked to IE.

  18. Inherited Variation in Cytokine, Acute Phase Response, and Calcium Metabolism Genes Affects Susceptibility to Infective Endocarditis

    Science.gov (United States)

    Rutkovskaya, Natalia V.; Kondyukova, Natalia V.; Odarenko, Yuri N.; Kazachek, Yana V.; Tsepokina, Anna V.; Barbarash, Leonid S.

    2017-01-01

    Infective endocarditis (IE) is a septic inflammation of the endocardium. Recognition of microbial patterns, cytokine and acute phase responses, hemostasis features, and alterations in plasma lipid and calcium profile all have been reported to affect pathogenesis and clinical course of IE. Having recruited 123 patients with IE and 300 age-, sex-, and ethnicity-matched healthy blood donors, we profiled their genomic DNA for 35 functionally significant polymorphisms within the 22 selected genes involved in the abovementioned pathways, with the further genetic association analysis. We found that the G/A genotype of the rs1143634 polymorphism within the IL1B gene, the G/T genotype of the rs3212227 polymorphism within the IL12B gene, the A/G genotype of the rs1130864 polymorphism within the CRP gene, and the G allele of the rs1801197 polymorphism within the CALCR gene were associated with a decreased risk of IE whereas the T/T genotype of the rs1205 polymorphism within the CRP gene was associated with a higher risk of IE. Furthermore, heterozygous genotypes of the rs1143634 and rs3212227 polymorphisms were associated with the higher plasma levels of IL-1β and IL-12, respectively. Our results indicate that inherited variation in the cytokine, acute phase response, and calcium metabolism pathways may be linked to IE. PMID:28659664

  19. Response to Dengue virus infections altered by cytokine-like substances from mosquito cell cultures

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    Laosutthipong Chaowanee

    2010-11-01

    Full Text Available Abstract Background With both shrimp and commercial insects such as honey bees, it is known that stable, persistent viral infections characterized by absence of disease can sometimes shift to overt disease states as a result of various stress triggers and that this can result in serious economic losses. The main research interest of our group is to understand the dynamics of stable viral infections in shrimp and how they can be destabilized by stress. Since there are no continuous cell lines for crustaceans, we have used a C6/36 mosquito cell line infected with Dengue virus to test hypotheses regarding these interactions. As a result, we accidentally discovered two new cytokine-like substances in 5 kDa extracts from supernatant solutions of acutely and persistently infected mosquito cells. Results Naïve C6/36 cells were exposed for 48 h to 5 kDa membrane filtrates prepared from the supernatant medium of stable C6/36 mosquito cell cultures persistently-infected with Dengue virus. Subsequent challenge of naïve cells with a virulent stock of Dengue virus 2 (DEN-2 and analysis by confocal immunofluorescence microscopy using anti-DEN-2 antibody revealed a dramatic reduction in the percentage of DEN-2 infected cells when compared to control cells. Similar filtrates prepared from C6/36 cells with acute DEN-2 infections were used to treat stable C6/36 mosquito cell cultures persistently-infected with Dengue virus. Confocal immunofluorescence microscopy revealed destabilization in the form of an apoptosis-like response. Proteinase K treatment removed the cell-altering activities indicating that they were caused by small polypeptides similar to those previously reported from insects. Conclusions This is the first report of cytokine-like substances that can alter the responses of mosquito cells to Dengue virus. This simple model system allows detailed molecular studies on insect cytokine production and on cytokine activity in a standard insect cell line.

  20. Response of air cleaning system dampers and blowers to simulated tornado transients

    International Nuclear Information System (INIS)

    Gregory, W.; Idar, E.; Smith, P.; Hensel, E.; Smith, E.

    1985-01-01

    The effects of tornado-like pressure transients upon dampers and blowers in nuclear air cleaning systems were studied. For the dampers pressure drop as a function of flow rate was obtained and an empirical relationship developed. Transient response was examined for several types of dampers, as was structural integrity. Both centrifugal and axi-vane blowers were tested and transient characteristic curves were generated in outrunning and backflow situations. The transient characteristic curves do not necessarily match the quasi-steady characteristic curves

  1. The Effect of C. burnetii Infection on the Cytokine Response of PBMCs from Pregnant Goats

    Science.gov (United States)

    Ammerdorffer, Anne; Roest, Hendrik-I J.; Dinkla, Annemieke; Post, Jacob; Schoffelen, Teske; van Deuren, Marcel; Sprong, Tom; Rebel, Johanna M.

    2014-01-01

    In humans, infection with Coxiella burnetii, the causative agent of Q fever, leads to acute or chronic infection, both associated with specific clinical symptoms. In contrast, no symptoms are observed in goats during C. burnetii infection, although infection of the placenta eventually leads to premature delivery, stillbirth and abortion. It is unknown whether these differences in clinical outcome are due to the early immune responses of the goats. Therefore, peripheral blood mononuclear cells (PBMCs) were isolated from pregnant goats. In total, 17 goats were included in the study. Six goats remained naive, while eleven goats were infected with C. burnetii. Toll-like receptor (TLR) and cytokine mRNA expression were measured after in vitro stimulation with heat-killed C. burnetii at different time points (prior infection, day 7, 35 and 56 after infection). In naive goats an increased expression of interleukin (IL)-1β, tumor necrosis factor (TNF)-α, IL-10 and interferon (IFN)-γ mRNA upon C. burnetii stimulation was detected. In addition, TLR2 expression was strongly up-regulated. In goats infected with C. burnetii, PBMCs re-stimulated in vitro with C. burnetii, expressed significantly more TNF-α mRNA and IFN-γ mRNA compared to naive goats. In contrast, IL-10 mRNA production capacity was down-regulated during C. burnetii infection. Interestingly, at day 7 after inoculation a decreased IFN-γ protein level was observed in stimulated leukocytes in whole blood from infected goats, whereas at other time-points increased production of IFN-γ protein was seen. Our study shows that goats initiate a robust pro-inflammatory immune response against C. burnetii in vitro. Furthermore, PBMCs from C. burnetii infected goats show augmented pro-inflammatory cytokine responses compared to PBMCs from non-infected goats. However, despite this pro-inflammatory response, goats are not capable of clearing the C. burnetii infection. PMID:25279829

  2. Improved Transient Response Estimations in Predicting 40 Hz Auditory Steady-State Response Using Deconvolution Methods

    Directory of Open Access Journals (Sweden)

    Xiaodan Tan

    2017-12-01

    Full Text Available The auditory steady-state response (ASSR is one of the main approaches in clinic for health screening and frequency-specific hearing assessment. However, its generation mechanism is still of much controversy. In the present study, the linear superposition hypothesis for the generation of ASSRs was investigated by comparing the relationships between the classical 40 Hz ASSR and three synthetic ASSRs obtained from three different templates for transient auditory evoked potential (AEP. These three AEPs are the traditional AEP at 5 Hz and two 40 Hz AEPs derived from two deconvolution algorithms using stimulus sequences, i.e., continuous loop averaging deconvolution (CLAD and multi-rate steady-state average deconvolution (MSAD. CLAD requires irregular inter-stimulus intervals (ISIs in the sequence while MSAD uses the same ISIs but evenly-spaced stimulus sequences which mimics the classical 40 Hz ASSR. It has been reported that these reconstructed templates show similar patterns but significant difference in morphology and distinct frequency characteristics in synthetic ASSRs. The prediction accuracies of ASSR using these templates show significant differences (p < 0.05 in 45.95, 36.28, and 10.84% of total time points within four cycles of ASSR for the traditional, CLAD, and MSAD templates, respectively, as compared with the classical 40 Hz ASSR, and the ASSR synthesized from the MSAD transient AEP suggests the best similarity. And such a similarity is also demonstrated at individuals only in MSAD showing no statistically significant difference (Hotelling's T2 test, T2 = 6.96, F = 0.80, p = 0.592 as compared with the classical 40 Hz ASSR. The present results indicate that both stimulation rate and sequencing factor (ISI variation affect transient AEP reconstructions from steady-state stimulation protocols. Furthermore, both auditory brainstem response (ABR and middle latency response (MLR are observed in contributing to the composition of ASSR but

  3. Psychological stress exerts effects on pathogenesis of hepatitis B via type-1/type-2 cytokines shift toward type-2 cytokine response.

    Directory of Open Access Journals (Sweden)

    YingLi He

    Full Text Available BACKGROUND: Psychological and physical stress has been demonstrated to have an impact on health through modulation of immune function. Despite high prevalence of stress among patients with hepatitis B virus (HBV infection, little is known about whether and how stress exerts an effect on the course of hepatitis B. METHODS: Eighty patients with chronic hepatitis B(CHB completed the Perceived Stress Scale-10(PSS-10 and State-Trait Anxiety Inventory(STAI. Fresh whole blood was subject to flow cytometry for lymphocytes count. Plasma samples frozen at -80 °C were thawed for cytokines, alanine aminotransferase (ALT, and virus load. These patients were grouped into high or low perceived stress, state anxiety and trait anxiety groups according to the scale score. Sociodemographic, disease-specific characteristics, lymphocytes count and cytokines were compared. RESULTS: Firstly, a negative association between ALT and stress (t =  -4.308; p =  .000, state anxiety (t =  -3.085; p =  .003 and trait anxiety (t =  -4.925; p =  .000 were found. As ALT is a surrogate marker of hepatocytes injury, and liver injury is a consequence of immune responses. Next, we tested the relationship between stress/anxiety and lymphocytes. No statistical significance were found with respect to counts of total T cells, CD4+ T cell, CD8+ T cell, NK cell, and B cell count between high and low stress group. Type-2 cytokine interleukin-10 (IL-10 level was significantly higher in high stress group relative to lower counterpart (t = 6.538; p = 0.000, and type-1 cytokine interferon-gamma (IFN-γ level shown a decreased tendency in high stress group (t =  -1.702; p = 0.093. Finally, INF-γ:IL-10 ratio displayed significant decrease in high perceived stress(t =  -4.606; p = 0.000, state anxiety(t =  -5.126; p = 0.000 and trait anxiety(t =  -4.670; p = 0.000 groups relative to low counterparts. CONCLUSION: Our data show stress is not related to the lymphocyte cells

  4. Gene expression of hematoregulatory cytokines is elevated endogenously after sublethal gamma irradiation and is differentially enhanced by therapeutic administration of biologic response modifiers

    International Nuclear Information System (INIS)

    Peterson, V.M.; Adamovicz, J.J.; Madonna, G.S.; Gause, W.C.; Elliott, T.B.; Moore, M.M.; Ledney, G.D.; Jackson, W.E. III

    1994-01-01

    Prompt, cytokine-mediated restoration of hematopoiesis is a prerequisite for survival after irradiation. Therapy with biologic response modifiers (BRMs), such as LPS, 3D monophosphoryl lipid A (MPL), and synthetic trehalose dicrynomycolate (S-TDCM) presumably accelerates hematopoietic recovery after irradiation are poorly defined. One hour after sublethal (7.0 Gy) 60 Co gamma irradiation, B6D2F1/J female mice received a single i.p. injection of LPS, MPL, S-TDCM, an extract from Serratia marcescens (Sm-BRM), or Tween 80 in saline (TS). Five hours later, a quantitative reverse transcription-PCR assay demonstrated marked splenic gene expression for IL-1β, IL-3, IL-6, and granulocyte-CSF (G-CSF). Enhanced gene expression for TNF-α, macrophage-CSF (M-CSF), and stem cell factor (SCF) was not detected. Injection of any BRM further enhanced cytokine gene expression and plasma levels of CSF activity within 24 h after irradiation and hastened bone marrow recovery. Mice injected with S-TDCM or Sm-BRM sustained expression of the IL-6 gene for at least 24 h after irradiation. Sm-BRM-treated mice exhibited greater gene expression for IL-1β, IL-3, TNF-α, and G-CSF at day 1 than any other BRM. When challenged with 2 LD 50/30 of Klebsiella pneumoniae 4 days after irradiation, 100% of Sm-BRM-treated mice and 70% of S-TDCM-treated mice survived, whereas ≤30% of mice treated with LPS, MPL, or TS survived. Thus, sublethal irradiation induces transient, splenic cytokine gene expression that can be differentially amplified and prolonged by BRMs. BRMs that sustained and/or enhanced irradiation-induced expression of specific cytokine genes improved survival after experimental infection. 67 refs., 7 figs., 1 tab

  5. Integration of the thiol redox status with cytokine response to physical training in professional basketball players.

    Science.gov (United States)

    Zembron-Lacny, A; Slowinska-Lisowska, M; Ziemba, A

    2010-01-01

    The present study was designed to evaluate the plasma markers of reactive oxygen species (ROS) activity and cytokines, and their relationship with thiol redox status of basketball players during training. Sixteen professional players of the Polish Basketball Extraleague participated in the study. The study was performed during the preparatory period and the play-off round. Markers of ROS activity (lipid peroxidation TBARS, protein carbonylation PC) and reduced glutathione (GSH) demonstrated regularity over time, i.e. TBARS, PC and GSH were elevated at the beginning and decreased at the end of training periods. Oxidized glutathione (GSSG) was not affected by exercise training. Thiol redox status (GSH(total)-2GSSG/GSSG) correlated with TBARS and PC in both training periods. The level of interleukin-6 (IL-6) was increased and positively correlated with thiol redox (r=0.423) in the preparatory period, whereas tumor necrosis factor alpha (TNFalpha) was increased and inversely correlated with thiol redox (r= 0.509) in the play-off round. The present study showed significant shifts in markers of ROS activity, thiol redox status and inflammatory mediators (IL-6, TNFalpha) following professional sport training as well as correlation between changes in thiol redox and cytokine response.

  6. Transient response of Babcock and Wilcox-designed reactors

    International Nuclear Information System (INIS)

    1980-05-01

    On February 26, 1980, the Crystal River Unit No. 3 Nuclear Generating Plant, designed by the Babcock and Wilcox Company (B and W), experienced an incident involving a malfunction in an instrumentation and control system power supply. Faced with the Crystal River Unit 3 incident and the apparently high frequency of such near similar types of transients in other B and W designed plants, a special Task Force was established within the Office of Nuclear Reactor Regulation to provide an assessment of the apparent sensitivity of the B and W designed plants to such transients and the consequences of malfunctions and failures of the integrated control system and non-nuclear instrumentation. This report provides an assessment of these issues

  7. PWR [pressurized water reactor] pressurizer transient response: Final report

    International Nuclear Information System (INIS)

    Murphy, S.I.

    1987-08-01

    To predict PWR pressurizer transients, Ahl proposed a three region model with a universal coefficient to represent condensation on the water surface. Specifically, this work checks the need for three regions and the modeling of the interfacial condensation coefficient. A computer model has been formulated using the basic mass and energy conservation laws. A two region vapor and liquid model was first used to predict transients run on a one-eleventh scale Freon pressurizer. These predictions verified the need for a second liquid region. As a result, a three region model was developed and used to predict full-scale pressurizer transients at TMI-2, Shippingport, and Stade. Full-scale pressurizer predictions verified the three region model and pointed out the shortcomings of Ahl's universal condensation coefficient. In addition, experiments were run using water at low pressure to study interface condensation. These experiments showed interface condensation to be significant only when spray flow is turned on; this result was incorporated in the final three region model

  8. Virulent Type A Francisella tularensis actively suppresses cytokine responses in human monocytes

    Directory of Open Access Journals (Sweden)

    Devyn D Gilette

    2014-04-01

    Full Text Available Francisella tularensis is a Gram-negative facultative bacterium that can cause the disease tularemia, even upon exposure to low numbers of bacteria. One critical characteristic of Francisella is its ability to dampen or subvert the host immune response. Previous work has shown that monocytes infected with highly virulent F. tularensis subsp. tularensis strain Schu S4 responded with a general pattern of quantitatively reduced pro-inflammatory signaling pathway genes and cytokine production in comparison to those infected with the less virulent related F. novicida. However, it has been unclear whether the virulent Schu S4 was merely evading or actively suppressing monocyte responses. By using mixed infection assays with F. tularensis and F. novicida, we show that F. tularensis actively suppresses monocyte pro-inflammatory responses. Additional experiments show that this suppression occurs in a dose-dependent manner and is dependent upon the viability of F. tularensis. Importantly, F. tularensis was able to suppress pro-inflammatory responses to earlier infections with F. novicida. These results lend support that F. tularensis actively dampens human monocyte responses and this likely contributes to its enhanced pathogenicity.

  9. Analysis of SF and plasma cytokines provides insights into the mechanisms of inflammatory arthritis and may predict response to therapy.

    Science.gov (United States)

    Wright, Helen L; Bucknall, Roger C; Moots, Robert J; Edwards, Steven W

    2012-03-01

    Biologic drugs have revolutionized the care of RA, but are expensive and not universally effective. To further understand the inflammatory mechanisms underlying RA and identify potential biomarkers predicting response to therapy, we measured multiple cytokine concentrations in SF of patients with inflammatory arthritides (IAs) and, in a subset of patients with RA, correlated this with response to TNF-α inhibition. SF from 42 RA patients and 19 non-RA IA patients were analysed for 12 cytokines using a multiplex cytokine assay. Cytokines were also measured in the plasma of 16 RA patients before and following treatment with anti-TNF-α. Data were analysed using Mann-Whitney U-test, Spearman's rank correlation and cluster analysis with the Kruskal-Wallis test with Dunn's post-test analysis. RA SF contained significantly elevated levels of IL-1β, IL-1ra, IL-2, IL-4, IL-8, IL-10, IL-17, IFN-γ, G-CSF, GM-CSF and TNF-α compared with other IA SF. RA patients who did not respond to anti-TNF therapy had elevated IL-6 in their SF pre-therapy (P < 0.05), whereas responders had elevated IL-2 and G-CSF (P < 0.05). Plasma cytokine concentrations were not significantly modulated by TNF inhibitors, with the exception of IL-6, which decreased after 12 weeks (P < 0.05). Cytokine profiles in RA SF vary with treatment and response to therapy. Cytokine concentrations are significantly lower in plasma than in SF and relatively unchanged by TNF inhibitor therapy. Concentrations of IL-6, IL-2 and G-CSF in SF may predict response to TNF inhibitors.

  10. Electrical and optical response of a laser diode to transient ionizing radiation

    International Nuclear Information System (INIS)

    Baggio, J.; Brisset, C.; Sommer, J.L.; D'hose, C.; Lalande, P.; Leray, J.L.; Musseau, O.

    1996-01-01

    The authors have studied transient irradiation effects on the optical and electrical responses of a laser diode. The influence of dose rate, ranging from 10 9 to 10 12 rad(Si)/s, has been investigated through a complete experimental study. Dose rate vulnerability of the laser diode has been observed. Electrical and optical transient responses are determined by the dose rate, the diode structure, and its operating point

  11. Transient voltage response of a superconducting strip to a supercritical current pulse

    International Nuclear Information System (INIS)

    Attekum, P.M.Th.M. van; Wouters, M.C.H.M.; Wolter, J.; Horstman, R.E.

    1981-01-01

    A superconductor subject to a supercritical current pulse displays a delay time between the onset of the current pulse and the onset of the corresponding voltage response. From the onset of the voltage response it takes a second (transient) time to reach the stationary state. It is shown that the transient time can be explained with inhomogeneities in the strip which give rise to a distribution of delay times. The transient time is thus not related to a characteristic time in the superconductor. For small supercritical currents also heating effects show up. (author)

  12. The effect of Platelet Lysate on osteoblast proliferation associated with a transient increase of the inflammatory response in bone regeneration.

    Science.gov (United States)

    Ruggiu, Alessandra; Ulivi, Valentina; Sanguineti, Francesca; Cancedda, Ranieri; Descalzi, Fiorella

    2013-12-01

    Platelet Lysate (PL) contains a cocktail of growth factors and cytokines, which actively participates in tissue repair and its clinical application has been broadly described. The aim of this study was to assess the regenerative potential of PL for bone repair. We demonstrated that PL stimulation induces a transient increase of the inflammatory response in quiescent human osteoblasts, via NF-kB activation, COX-2 induction, PGE2 production and secretion of pro-inflammatory cytokines. Furthermore, we showed that long-term PL stimulation enhances proliferation of actively replicating osteoblasts, without affecting their differentiation potential, along with changes of cell morphology, resulting in increased cell density at confluence. In confluent resting osteoblasts, PL treatment induced resumption of proliferation, change in cell morphology and increase of cell density at confluence. A burst of PL treatment (24-h) was sufficient to trigger such processes in both conditions. These results correlated with up-regulation of the proliferative and survival pathways ERKs and Akt and with cell cycle re-activation via induction of CyclinD1 and phosphorylation of Rb, following PL stimulation. Our findings demonstrate that PL treatment results in activation and expansion of resting osteoblasts, without affecting their differentiation potential. Therefore PL represents a good therapeutic candidate in regenerative medicine for bone repair. Copyright © 2013 Elsevier Ltd. All rights reserved.

  13. Response of the human tympanic membrane to transient acoustic and mechanical stimuli: Preliminary results

    Science.gov (United States)

    Razavi, Payam; Ravicz, Michael E.; Dobrev, Ivo; Cheng, Jeffrey Tao; Furlong, Cosme; Rosowski, John J.

    2016-01-01

    The response of the tympanic membrane (TM) to transient environmental sounds and the contributions of different parts of the TM to middle-ear sound transmission were investigated by measuring the TM response to global transients (acoustic clicks) and to local transients (mechanical impulses) applied to the umbo and various locations on the TM. A lightly-fixed human temporal bone was prepared by removing the ear canal, inner ear, and stapes, leaving the incus, malleus, and TM intact. Motion of nearly the entire TM was measured by a digital holography system with a high speed camera at a rate of 42 000 frames per second, giving a temporal resolution of <24 μs for the duration of the TM response. The entire TM responded nearly instantaneously to acoustic transient stimuli, though the peak displacement and decay time constant varied with location. With local mechanical transients, the TM responded first locally at the site of stimulation, and the response spread approximately symmetrically and circumferentially around the umbo and manubrium. Acoustic and mechanical transients provide distinct and complementary stimuli for the study of TM response. Spatial variations in decay and rate of spread of response imply local variations in TM stiffness, mass, and damping. PMID:26880098

  14. Newborn hearing screening with transient evoked otoacoustic emissions and automatic auditory brainstem response

    Directory of Open Access Journals (Sweden)

    Renata Mota Mamede de Carvallo

    2008-09-01

    Full Text Available Objective: The aim of the present investigation was to check Transient Evoked Otoacoustic Emissions and Automatic Auditory Brainstem Response tests applied together in regular nurseries and Newborn Intensive Care Units (NICU, as well as to describe and compare the results obtained in both groups. Methods: We tested 150 newborns from regular nurseries and 70 from NICU. Rresults: The newborn hearing screening results using Transient Evoked Otoacoustic Emissions and Automatic Auditory Brainstem Response tests could be applied to all babies. The “pass” result for the group of babies from the nursery was 94.7% using Transient Evoked Otoacoustic Emissions and 96% using Automatic Auditory Brainstem Response. The newborn intensive care unit group obtained 87.1% on Transient Evoked Otoacoustic Emissions and 80% on the Automatic Auditory Brainstem Response, and there was no statistical difference between the procedures when the groups were evaluated individually. However, comparing the groups, Transient Evoked Otoacoustic Emissions were presented in 94.7% of the nursery babies and in 87.1% in the group from the newborn intensive care unit. Considering the Automatic Auditory Brainstem Response, we found 96 and 87%, respectively. Cconclusions: Transient Evoked Otoacoustic Emissions and Automatic Auditory Brainstem Response had similar “pass” and “fail” results when the procedures were applied to neonates from the regular nursery, and the combined tests were more precise to detect hearing impairment in the newborn intensive care unit babies.

  15. Cytokine Gene Expression in Response to SnSAG1 in Horses with Equine Protozoal Myeloencephalitis

    Science.gov (United States)

    Spencer, Jennifer A.; Deinnocentes, Patricia; Moyana, Edith M.; Guarino, Anthony J.; Ellison, Siobhan E.; Bird, R. Curtis; Blagburn, Byron L.

    2005-01-01

    Equine protozoal myeloencephalitis (EPM) is a neurologic syndrome seen in horses from the Americas and is mainly caused by Sarcocystis neurona. Recently, a 29-kDa surface antigen from S. neurona merozoites was identified as being highly immunodominant on a Western blot. This antigen has been sequenced and cloned, and the expressed protein has been named SnSAG1. In a previous study, cell-mediated immune responses to SnSAG1 were shown to be statistically significantly reduced in horses with EPM in comparison to EPM-negative control horses. It therefore appears as though the parasite is able to induce immunosuppression towards parasite-derived antigens as parasite-specific responses are decreased. Isolated peripheral blood lymphocytes from 21 EPM (cerebrospinal fluid [CSF] Western blot)-negative horses with no clinical signs and 21 horses with clinical signs of EPM (CSF Western blot positive) were cocultured with SnSAG1 for 48 and 72 h, and the effect on cytokine production was investigated by means of reverse transcriptase PCR. Cytokines assayed include gamma interferon (IFN-γ), tumor necrosis factor alpha, interleukin (IL)-2, IL-4, and IL-6. β-Actin was used as the housekeeping gene. A Wilcoxon signed-rank test of the findings indicated that there was a statistically significant decrease in IFN-γ production after 48 h in culture for samples from horses with clinical disease. There was also a statistically significant increase in IL-4 production after 72 h in culture for samples from horses with EPM. These results further support the notion that this parasite is able to subvert the immune system in horses with clinical disease. PMID:15879026

  16. Transient response of two lobe aerodynamic journal bearing

    Directory of Open Access Journals (Sweden)

    Saurabh Kumar Yadav

    2018-03-01

    Full Text Available The dynamic behavior of a rotor-dynamic system is greatly affected by the performance of aerodynamic bearing and the performance of bearing is characterized by the stiffness and damping coefficients. In the present work, stiffness and damping coefficients of bearing are computed and the performance of the bearing is greatly changed with the change in bearing air film profile. The effect of lobe offset factors on the transient performance of aerodynamic bearing is presented. Bifurcation and Poincare diagrams of two lobe journal bearing have been presented for different offset factors. A bearing designer can judge the bearing performance based on bifurcation diagrams.

  17. Association of brain injury and neonatal cytokine response during therapeutic hypothermia in newborns with hypoxic-ischemic encephalopathy.

    Science.gov (United States)

    Orrock, Janet E; Panchapakesan, Karuna; Vezina, Gilbert; Chang, Taeun; Harris, Kari; Wang, Yunfei; Knoblach, Susan; Massaro, An N

    2016-05-01

    Cytokines have been proposed as mediators of neonatal brain injury via neuroinflammatory pathways triggered by hypoxia-ischemia. Limited data are available on cytokine profiles in larger cohorts of newborns with hypoxic-ischemic encephalopathy (HIE) undergoing therapeutic hypothermia (TH). Serum cytokines interleukin (IL)-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-13, tumor necrosis factor-α, and interferon-γ were measured in newborns with HIE at 24 and 72 h of TH. Differences between infants with favorable (survivors with mild/no magnetic resonance imaging (MRI) injury) vs. adverse outcome (death or moderate/severe MRI injury) were compared using mixed models to adjust for covariates. Data from 36 term newborns with HIE (favorable outcome: n = 20, adverse outcome: n = 16) were evaluated. Cytokines IL-1β, IL-2, IL-6, IL-8, IL-10, and IL-13 were elevated in the adverse relative to favorable outcome group at 24 h. IL-6 remained significantly elevated in the adverse outcome group at 72 h. IL-6 and IL-10 remained significantly associated with outcome group after controlling for covariates. Inflammatory cytokines are elevated in HIE newborns with brain injury by MRI. In particular, IL-6 and IL-10 were associated with adverse outcomes after controlling for baseline characteristics and severity of presentation. These data suggest that cytokine response may identify infants in need of additional neuroprotective interventions.

  18. In vitro cytokine responses to periodontal pathogens: generalized aggressive periodontitis is associated with increased IL-6 response to Porphyromonas gingivalis

    DEFF Research Database (Denmark)

    Borch, T S; Holmstrup, Palle; Bendtzen, K

    2010-01-01

    with GAgP and 10 controls stimulated with periodontal pathogens or a control antigen, tetanus toxoid (TT) in the presence of autologous serum. The pathogens used were Porphyromonas gingivalis, Prevotella intermedia and Fusobacterium nucleatum, either as type strains or bacteria isolated from...... the participants' inherent oral flora. The P. gingivalis -induced production of IL-6 was approximately 2.5-fold higher in patients with GAgP than in healthy controls (P gingivalis, as all cytokine...... responses induced by Pr. intermedia, F. nucleatum and TT was similar in the two groups. A reduced IL-12p70 response to Pr. intermedia and F. nucleatum was observed in smokers compared to non-smoking patients (P gingivalis, MNC...

  19. A comparison of cytokine responses during prolonged cycling in normal and hot environmental conditions

    Directory of Open Access Journals (Sweden)

    Ludmila M Cosio-Lima

    2011-01-01

    Full Text Available Ludmila M Cosio-Lima, Bhargav V Desai, Petra B Schuler, Lesley Keck, Logan ScheelerDepartment of Health, Leisure, and Exercise Science, University of West Florida, Pensacola, FL, USAPurpose: Components of immune function are affected by physical activity in an adverse environment. The purpose of this study was to compare plasma differences in inflammatory cytokines including tumor necrosis factor α (TNF-α and interleukin 6 (IL-6, in addition to the stress hormone cortisol, during prolonged cycling under normal and hot environmental conditions in elite cyclists.Methods and design: Six trained elite male cyclists (27 ± 8 years; 75.5 ± 4 kg; maximum oxygen uptake [VO2max] = 66 ± 6 mL/kg/min, mean ± SD. The cyclists biked for 2.5 h at their prescribed 60% maximum exercise workload (Wmax or 75% VO2max either in an environmental chamber set at 15°C and 40% relative humidity (NEUTRAL or at 35°C and 40% relative humidity (HOT. The cyclists were given 4 mL of water/kg body weight every 15 min under both conditions.Results: Total cortisol concentrations were elevated (P < 0.05 immediately postexercise and 12 h postexercise in both the NEUTRAL and HOT conditions. TNF-α concentrations were only significantly (P = 0.045 elevated postexercise in HOT conditions. During the HOT conditions, a significant (P = 0.006 and 0.007, respectively difference in IL-6 was seen immediately after and 12 h postexercise. During the NEUTRAL condition, IL-6 was only significantly elevated postexercise (P < 0.05.Conclusions: Heat exposure during a long bout of exercise is sufficient to elicit stress response in elite cyclists. However, the degree of release of anti-inflammatory and proinflammatory cytokines might be related to several factors that include the athlete’s fitness level, hydration status, exercise intensity, and length of exposure to hot environments.Keywords: cytokines, inflammation, heat, exercise, performance 

  20. Cytokine responses to two common respiratory pathogens in children are dependent on interleukin-1β

    Directory of Open Access Journals (Sweden)

    Alice C-H. Chen

    2017-10-01

    Full Text Available Protracted bacterial bronchitis (PBB in young children is a common cause of prolonged wet cough and may be a precursor to bronchiectasis in some children. Although PBB and bronchiectasis are both characterised by neutrophilic airway inflammation and a prominent interleukin (IL-1β signature, the contribution of the IL-1β pathway to host defence is not clear. This study aimed to compare systemic immune responses against common pathogens in children with PBB, bronchiectasis and control children and to determine the importance of the IL-1β pathway. Non-typeable Haemophilus influenzae (NTHi stimulation of peripheral blood mononuclear cells (PBMCs from control subjects (n=20, those with recurrent PBB (n=20 and bronchiectasis (n=20 induced high concentrations of IL-1β, IL-6, interferon (IFN-γ and IL-10. Blocking with an IL-1 receptor antagonist (IL-1Ra modified the cellular response to pathogens, inhibiting cytokine synthesis by NTHi-stimulated PBMCs and rhinovirus-stimulated PBMCs (in a separate PBB cohort. Inhibition of IFN-γ production by IL-1Ra was observed across multiple cell types, including CD3+ T cells and CD56+ NK cells. Our findings highlight the extent to which IL-1β regulates the cellular immune response against two common respiratory pathogens. While blocking the IL-1β pathway has the potential to reduce inflammation, this may come at the cost of protective immunity against NTHi and rhinovirus.

  1. T cell cytokine responses to stimulation with Ureaplasma parvum in pregnancy.

    Science.gov (United States)

    Friedland, Yael D; Lee-Pullen, Tracey F; Nathan, Elizabeth A; Watts, Rory; Keelan, Jeffrey A; Payne, Matthew S; Ireland, Demelza J

    2016-08-01

    Ureaplasma spp. are a common vaginal microorganism causally linked to inflammation-driven preterm birth (PTB). The nature of the immune response to Ureaplasma spp. may influence PTB risk. This study sought to define maternal T cell cytokine responses to in vitro stimulation with Ureaplasma parvum serovar 3 (UpSV3) in vaginally colonised (UP+) and non-colonised (UP-) pregnant women. Whole blood flow cytometry demonstrated an increase (p=0.027) in the baseline frequency of IFNγ-positive CD3(+)CD4(-)(CD8(+)) T cells in UP+ women. UpSV3 stimulation resulted in a significant and specific increase (p=0.001) in the frequency of IFNγ-positive CD3(+)CD4(-)(CD8(+)) T cells, regardless of vaginal colonisation status. UpSV3 stimulation also increased the frequency of IFNγ-positive CD3(+)CD4(+) T cells, particularly in the UP+ group (p=0.003). This is the first published study to examine T cell responses to Ureaplasma spp. Future appropriately-powered studies are needed to assess whether insufficient priming or a loss of tolerance to Ureaplasma spp. is occurring in UP+ women at risk of PTB. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  2. Natural innate cytokine response to immunomodulators and adjuvants in human precision-cut lung slices.

    Science.gov (United States)

    Switalla, S; Lauenstein, L; Prenzler, F; Knothe, S; Förster, C; Fieguth, H-G; Pfennig, O; Schaumann, F; Martin, C; Guzman, C A; Ebensen, T; Müller, M; Hohlfeld, J M; Krug, N; Braun, A; Sewald, K

    2010-08-01

    Prediction of lung innate immune responses is critical for developing new drugs. Well-established immune modulators like lipopolysaccharides (LPS) can elicit a wide range of immunological effects. They are involved in acute lung diseases such as infections or chronic airway diseases such as COPD. LPS has a strong adjuvant activity, but its pyrogenicity has precluded therapeutic use. The bacterial lipopeptide MALP-2 and its synthetic derivative BPPcysMPEG are better tolerated. We have compared the effects of LPS and BPPcysMPEG on the innate immune response in human precision-cut lung slices. Cytokine responses were quantified by ELISA, Luminex, and Meso Scale Discovery technology. The initial response to LPS and BPPcysMPEG was marked by coordinated and significant release of the mediators IL-1β, MIP-1β, and IL-10 in viable PCLS. Stimulation of lung tissue with BPPcysMPEG, however, induced a differential response. While LPS upregulated IFN-γ, BPPcysMPEG did not. This traces back to their signaling pathways via TLR4 and TLR2/6. The calculated exposure doses selected for LPS covered ranges occurring in clinical studies with human beings. Correlation of obtained data with data from human BAL fluid after segmental provocation with endotoxin showed highly comparable effects, resulting in a coefficient of correlation >0.9. Furthermore, we were interested in modulating the response to LPS. Using dexamethasone as an immunosuppressive drug for anti-inflammatory therapy, we found a significant reduction of GM-CSF, IL-1β, and IFN-γ. The PCLS-model offers the unique opportunity to test the efficacy and toxicity of biological agents intended for use by inhalation in a complex setting in humans. Copyright © 2010 Elsevier Inc. All rights reserved.

  3. From transient response of a compact photobioreactor for microalgae cultivation

    Energy Technology Data Exchange (ETDEWEB)

    Dilay, Emerson; Ribeiro, Robert Luis Lara; Pulliam, Raevon; Mariano, Andre Bellin [Universidade Federal do Parana (UFPR), Curitiba, PR (Brazil). Nucleo de Pesquisa e Desenvolvimento em Energia Auto-Sustentavel; Ordonez, Juan Carlos [Florida State University, Tallahassee, FL (United States). Dept. of Mechanical Engineering and Center for Advanced Power Systems], E-mail: ordonez@caps.fsu.edu; Vargas, Jose Viriato Coelho [Universidade Federal do Parana (UFPR), Curitiba, PR (Brazil). Dept. de Engenharia Mecanica

    2010-07-01

    Biofuels from microalgae are currently the subject of funded scientific research in many countries due to their high productivity of oil when compared with other crops. Microalgae can also be used in many important applications such as to obtain compounds of interest for food, chemicals, and pharmaceuticals. The high productivity of microalgae when compared with other crops is achieved because agricultural land is not mandatory for their cultivation, since they can be grown in open ponds, sea or vertical photo bioreactors. In this paper, a mathematical model is introduced for assessing the transient microalgae growth as a function of variable light intensity, temperature and environmental conditions in the daily cycle. Photo bioreactor geometry is considered as well. Light intensity is obtained from sun position, photo bioreactor geometry, and the installation location in the world. The photo bioreactor was discretized in space by the the volume element method. Balances of energy and species together with thermodynamics, heat transfer and chemistry empirical and theoretical correlations are applied to each volume element. Therefore, a system of ordinary differential equations with respect to time only is capable of delivering temperatures and concentrations as functions of space and time, even with a coarse mesh. The numerical results are capable of predicting the transient and steady state photo bioreactor biomass production with low computational time. Microalgae specific growth rate as a function of average light intensity inside the tubes and time was calculated. As a result, the model is expected to be a useful tool for simulation, design, and optimization of compact photo bioreactors. (author)

  4. Linear population allocation by bistable switches in response to transient stimulation.

    Science.gov (United States)

    Srimani, Jaydeep K; Yao, Guang; Neu, John; Tanouchi, Yu; Lee, Tae Jun; You, Lingchong

    2014-01-01

    Many cellular decision processes, including proliferation, differentiation, and phenotypic switching, are controlled by bistable signaling networks. In response to transient or intermediate input signals, these networks allocate a population fraction to each of two distinct states (e.g. OFF and ON). While extensive studies have been carried out to analyze various bistable networks, they are primarily focused on responses of bistable networks to sustained input signals. In this work, we investigate the response characteristics of bistable networks to transient signals, using both theoretical analysis and numerical simulation. We find that bistable systems exhibit a common property: for input signals with short durations, the fraction of switching cells increases linearly with the signal duration, allowing the population to integrate transient signals to tune its response. We propose that this allocation algorithm can be an optimal response strategy for certain cellular decisions in which excessive switching results in lower population fitness.

  5. Transient identification system with noising data and 'don't know' response

    International Nuclear Information System (INIS)

    Mol, Antonio C. de A.; Martinez, Aquilino S.; Schirru, Roberto

    2002-01-01

    In the last years, many different approaches based on neural network (NN) has been proposed for transient identification in nuclear power plants (NPP). Some of them focus the dynamic identification using recurrent neural networks however, they are not able to deal with unrecognized transients. Other kind of solution uses competitive learning in order to allow the 'don't know' response. In this case dynamic, dynamic features are not well represented. This work presents a new approach for neural network based transient identification which allows either dynamic identification and 'don't know'response. Such approach uses two multilayer neural networks trained with backpropagation algorithm. The first one is responsible for the dynamic identification. This NN uses, a short set (in a movable time window) of recent measurements of each variable avoiding the necessity of using starting events. The other one is used to validate the instantaneous identification (from the first net) through the validation of each variable. This net is responsible for allowing the system to provide 'don't know' response. In order to validate the method a NPP transient identification problem comprising 15 postulated accidents, simulated for a pressurized water reactor, was proposed in the validation process it has been considered noising data in other to evaluate the method robustness. Obtained results reveal the ability of the method in dealing with both dynamic identification of transients and correct 'don't know' response. In order to validate the method, a NPP transient identification problem comprising 15 postulated accidents simulated for a pressurized water reactor, was proposed in the validation process it has been considered noising data in order to evaluate the method robustness. Obtained results reveal the ability of the method in dealing with both dynamic identification of transients and correct 'don't know' response. (author)

  6. Human leukocyte antigen and cytokine receptor gene polymorphisms associated with heterogeneous immune responses to mumps viral vaccine.

    Science.gov (United States)

    Ovsyannikova, Inna G; Jacobson, Robert M; Dhiman, Neelam; Vierkant, Robert A; Pankratz, V Shane; Poland, Gregory A

    2008-05-01

    Mumps outbreaks continue to occur throughout the world, including in highly vaccinated populations. Vaccination against mumps has been successful; however, humoral and cellular immune responses to mumps vaccines vary significantly from person to person. We set out to assess whether HLA and cytokine gene polymorphisms are associated with variations in the immune response to mumps viral vaccine. To identify genetic factors that might contribute to variations in mumps vaccine-induced immune responses, we performed HLA genotyping in a group of 346 healthy schoolchildren (12-18 years of age) who previously received 2 doses of live mumps vaccine. Single-nucleotide polymorphisms (minor allele frequency of >5%) in cytokine and cytokine receptor genes were genotyped for a subset of 118 children. Median values for mumps-specific antibody titers and lymphoproliferative stimulation indices were 729 IU/mL and 4.8, respectively. Girls demonstrated significantly higher mumps antibody titers than boys, indicating gender-linked genetic differences in humoral immune response. Significant associations were found between the HLA-DQB1*0303 alleles and lower mumps-specific antibody titers. An interesting finding was the association of several HLA class II alleles with mumps-specific lymphoproliferation. Alleles of the DRB1 (*0101, *0301, *0801, *1001, *1201, and *1302), DQA1 (*0101, *0105, *0401, and *0501), and DQB1 (*0201, *0402, and *0501) loci were associated with significant variations in lymphoproliferative immune responses to mumps vaccine. Additional associations were observed with single-nucleotide polymorphisms in the interleukin-10RA, interleukin-12RB1, and interleukin-12RB2 cytokine receptor genes. Minor alleles for 4 single-nucleotide polymorphisms within interleukin-10RA and interleukin-12RB genes were associated with variations in humoral and cellular immune responses to mumps vaccination. These data suggest the important role of HLA and immunoregulatory cytokine receptor

  7. The transient response of a quantum wave to an instantaneous potential step switching

    Energy Technology Data Exchange (ETDEWEB)

    Delgado, F [Departamento de Quimica-Fisica, Universidad del Pais Vasco, Apdo 644, 48080 Bilbao (Spain); Cruz, H [Departamento de Fisica Basica, Universidad de La Laguna (Spain); Muga, J G [Departamento de Quimica-Fisica, Universidad del Pais Vasco, Apdo 644, 48080 Bilbao (Spain)

    2002-12-06

    The transient response of a stationary state of a quantum particle in a step potential to an instantaneous change in the step height (a simplified model for a sudden bias switch in an electronic semiconductor device) is solved exactly by means of a semianalytical expression. The characteristic times for the transient process up to the new stationary state are identified. A comparison is made between the exact results and an approximate method.

  8. Newborn hearing screening with transient evoked otoacoustic emissions and automatic auditory brainstem response

    OpenAIRE

    Renata Mota Mamede de Carvallo; Carla Gentile Matas; Isabela de Souza Jardim

    2008-01-01

    Objective: The aim of the present investigation was to check Transient Evoked Otoacoustic Emissions and Automatic Auditory Brainstem Response tests applied together in regular nurseries and Newborn Intensive Care Units (NICU), as well as to describe and compare the results obtained in both groups. Methods: We tested 150 newborns from regular nurseries and 70 from NICU. Rresults: The newborn hearing screening results using Transient Evoked Otoacoustic Emissions and Automatic Auditory Brainstem...

  9. Proinflammatory Cytokine Responses in Extra-Respiratory Tissues During Severe Influenza

    NARCIS (Netherlands)

    Short, Kirsty R; Veeris, Rebecca; Leijten, Lonneke M; van den Brand, Judith M; Jong, Victor L; Stittelaar, Koert J; Osterhaus, Ab D M E|info:eu-repo/dai/nl/074960172; Andeweg, Arno C; van Riel, Debby

    2017-01-01

    Severe influenza is often associated with disease manifestations outside the respiratory tract. While proinflammatory cytokines can be detected in the lungs and blood of infected patients, the role of extra-respiratory organs in the production of proinflammatory cytokines is unknown. Here, we show

  10. Proinflammatory Cytokine Responses in Extra-Respiratory Tissues during Severe Influenza

    NARCIS (Netherlands)

    Short, Kirsty R.; Veeris, Rebecca; Leijten, Lonneke M.; van den Brand, Judith M A; Jong, Victor L.; Stittelaar, Koert; Osterhaus, Ab D.M.E.; Andeweg, Arno C; Van Riel, Debby

    2017-01-01

    Severe influenza is often associated with disease manifestations outside the respiratory tract. While proinflammatory cytokines can be detected in the lungs and blood of infected patients, the role of extra-respiratory organs in the production of proinflammatory cytokines is unknown. Here, we show

  11. Effect of automatic recirculation flow control on the transient response for Lungmen ABWR plant

    Energy Technology Data Exchange (ETDEWEB)

    Tzang, Y.-C., E-mail: yctzang@aec.gov.t [National Tsing Hua University, Department of Engineering and System Science, Hsinchu 30013, Taiwan (China); Chiang, R.-F.; Ferng, Y.-M.; Pei, B.-S. [National Tsing Hua University, Department of Engineering and System Science, Hsinchu 30013, Taiwan (China)

    2009-12-15

    In this study the automatic mode of the recirculation flow control system (RFCS) for the Lungmen ABWR plant has been modeled and incorporated into the basic RETRAN-02 system model. The integrated system model is then used to perform the analyses for the two transients in which the automatic RFCS is involved. The two transients selected are: (1) one reactor internal pump (RIP) trip, and (2) loss of feedwater heating. In general, the integrated system model can predict well the response of key system parameters, including neutron flux, steam dome pressure, heat flux, RIP flow, core inlet flow, feedwater flow, steam flow, and reactor water level. The transients are also analyzed for manual RFCS case, between the automatic RFCS and the manual RFCS cases, comparisons of the transient response for the key system parameter show that the difference of transient response can be clearly identified. Also, the results show that the DELTACPR (delta critical power ratio) for the transients analyzed may not be less limiting for the automatic RFCS case under certain combination of control system settings.

  12. In vitro cytokine responses to periodontal pathogens: generalized aggressive periodontitis is associated with increased IL-6 response to Porphyromonas gingivalis

    DEFF Research Database (Denmark)

    Borch, T S; Holmstrup, Palle; Bendtzen, K

    2010-01-01

    the participants' inherent oral flora. The P. gingivalis -induced production of IL-6 was approximately 2.5-fold higher in patients with GAgP than in healthy controls (P production was non-significantly elevated. IL-1beta production induced by P. gingivalis, as all cytokine...... from two donors free of disease were stimulated with this bacterium in the presence of the various patient and control sera. An elevated IL-6 and TNF-alpha response was observed in the presence of patient sera (P production of IL-6......Generalized aggressive periodontitis (GAgP) is an inflammatory condition resulting in destruction of tooth-supporting tissues. We examined the production of IL-1beta, IL-6, tumour necrosis factor (TNF)-alpha, IL-12 and IL-10 in cultures of peripheral mononuclear cells (MNC) from 10 patients...

  13. Dysregulation of cytokine response in Canadian First Nations communities: is there an association with persistent organic pollutant levels?

    Directory of Open Access Journals (Sweden)

    Pascal Imbeault

    Full Text Available In vitro and animal studies report that some persistent organic pollutants (POPs trigger the secretion of proinflammatory cytokines. Whether POP exposure is associated with a dysregulation of cytokine response remains to be investigated in humans. We studied the strength of association between plasma POP levels and circulating cytokines as immune activation markers. Plasma levels of fourteen POPs and thirteen cytokines were measured in 39 Caucasians from a comparator sample in Québec City (Canada and 72 First Nations individuals from two northern communities of Ontario (Canada. Caucasians showed significantly higher levels of organochlorine insecticides (β-HCH, p,p'-DDE and HCB compared to First Nations. Conversely, First Nations showed higher levels of Mirex, Aroclor 1260, PCB 153, PCB 170, PCB 180 and PCB 187 compared to Caucasians. While there was no difference in cytokine levels of IL-4, IL-6, IL-10 and IL-22 between groups, First Nations had significantly greater average levels of IFNγ, IL-1β, IL-2, IL-5, IL-8, IL-12p70, IL-17A, TNFα and TNFβ levels compared to Caucasians. Among candidate predictor variables (age, body mass index, insulin resistance and POP levels, high levels of PCBs were the only predictor accounting for a small but significant effect of observed variance (∼7% in cytokine levels. Overall, a weak but significant association is detected between persistent organochlorine pollutant exposure and elevated cytokine levels. This finding augments the already existing information that environmental pollution is related to inflammation, a common feature of several metabolic disorders that are known to be especially prevalent in Canada's remote First Nations communities.

  14. Comparison of pressure transient response in intensely and sparsely fractured reservoirs

    Energy Technology Data Exchange (ETDEWEB)

    Johns, R.T.

    1989-04-01

    A comprehensive analytical model is presented to study the pressure transient behavior of a naturally fractured reservoir with a continuous matrix block size distribution. Geologically realistic probability density functions of matrix block size are used to represent reservoirs of varying fracture intensity and uniformity. Transient interporosity flow is assumed and interporosity skin is incorporated. Drawdown and interference pressure transient tests are investigated. The results show distinctions in the pressure response from intensely and sparsely fractured reservoirs in the absence of interporosity skin. Also, uniformly and nonuniformly fractured reservoirs exhibit distinct responses, irrespective of the degree of fracture intensity. The pressure response in a nonuniformly fractured reservoir with large block size variability, approaches a nonfractured (homogeneous) reservoir response. Type curves are developed to estimate matrix block size variability and the degree of fracture intensity from drawdown and interference well tests.

  15. A calibration method for PLLs based on transient response

    DEFF Research Database (Denmark)

    Cassia, Marco; Shah, Peter Jivan; Bruun, Erik

    2004-01-01

    A novel method to calibrate the frequency response of a Phase-Locked Loop is presented. The method requires just an additional digital counter and an auxiliary Phase-Frequency Detector (PFD) to measure the natural frequency of the PLL. The measured value can be used to tune the PLL response...

  16. A simulation model for transient response of a gas separation module using a hollow fiber membrane

    Energy Technology Data Exchange (ETDEWEB)

    Sugiyama, Takahiko, E-mail: t-sugiyama@nucl.nagoya-u.ac.jp [Nagoya University, Fro-cho, Chikusa-ku, Nagoya 464-8603 (Japan); Miyahara, Naoya [Nagoya University, Fro-cho, Chikusa-ku, Nagoya 464-8603 (Japan); Tanaka, Masahiro [National Institute for Fusion Science, Oroshi-cho 322-6, Toki 509-5292 (Japan); Munakata, Kenzo [Akita University, Tegata Gakuen-cho 1-1, Akita-shi, Akita 010-8502 (Japan); Yamamoto, Ichiro [Nagoya University, Fro-cho, Chikusa-ku, Nagoya 464-8603 (Japan)

    2011-10-15

    A simulation model has been developed for transient response of a gas separation module using a hollow fiber membrane for the removal of tritium from the atmosphere of the confinement space. The mass transfer process such as sorption and desorption of gases at the surface of the dense layer and the porous support layer, diffusive transfer in the both layers are treated in the model. Sorption isotherm, mass transfer rate and permeance are estimated through step-wise transient response experiments. The present model represents well not only separation factors and recovery ratio at the steady state but also responses to the multi-step wise change in the sweep gas rate.

  17. Human cytokine response to Texas crotaline envenomation before and after antivenom administration.

    Science.gov (United States)

    Crocker, Patrick; Zad, Omid; Milling, Truman; Maxson, Todd; King, Benjamin; Whorton, Elbert

    2010-10-01

    The aim of this study was to characterize the human cytokine response to Texas crotaline envenomation before and after antivenom administration. This study enrolled crotaline bite victims presenting to a regional trauma center and children's hospital from March to November 2007 and age-matched unbitten controls. Blood spot cards were obtained from bite victims at presentation and at 1 and 6 hours after antivenom administration. One control sample was drawn from each of the age-matched controls selected from urgent care patients presenting for minor complaints. Samples were delivered to a laboratory using a proprietary method for quantitative evaluation of a large number of biomarkers in parallel with bead-based multiplex immunoassays. After obtaining informed consent, 14 crotaline bite victims (age range, 5-85 years; median age, 45 years; 50% female) (Snakebite Severity Score, 2-7; median, 3) and 14 age-matched controls were enrolled. There were 7 copperhead (Agkistrodon contortrix) bites, 4 rattlesnake (probably Western Diamondback Crotalus atrox) bites, 2 cottonmouth (Agkistrodon piscivorus) bites, and 1 bite from a snake that was not identified by the victim. In t tests, the means in the presentation samples for apolipoprotein A-I (Apo A-I), Apo C3, interleukin 4 (IL-4), myeloperoxidase, plasminogen activator inhibitor 1 (PAI-1), epidermal growth factor, and regulated upon activation, normal t-cell expressed and secreted were significantly lower and Apo H was significantly higher in the bite patients than in the controls. In the 1-hour sample, α(1)-antitrypsin, Apo A-I, Apo C3, eotaxin, IL-4, myeloperoxidase, and PAI-1 levels were lower and prostatic acid phosphatase and cancer antigen 125 levels were higher in the bite patients than in the controls. And in the 6-hour sample, α(1)-antitrypsin, Apo A-I, Apo C3, endothelin-1, IL-4, macrophage inflammatory protein 1β, myeloperoxidase, and epidermal growth factor levels were lower and Apo H level was higher in

  18. Heavy metal mediated innate immune responses of the Indian green frog, Euphlyctis hexadactylus (Anura: Ranidae): Cellular profiles and associated Th1 skewed cytokine response

    International Nuclear Information System (INIS)

    Jayawardena, Uthpala A.; Ratnasooriya, Wanigasekara D.; Wickramasinghe, Deepthi D.; Udagama, Preethi V.

    2016-01-01

    Immune cell and cytokine profiles in relation to metal exposure though much studied in mammals has not been adequately investigated in amphibians, due mainly to lack of suitable reagents for cytokine profiling in non-model species. However, interspecies cross reactivity of cytokines permitted us to assay levels of IFNγ, TNFα, IL6 and IL10in a common anuran, the Indian green frog (Euphlyctis hexadactylus), exposed to heavy metals (Cd, Cr, Cu, Zn and Pb, at ~ 5 ppm each) under field and laboratory settings in Sri Lanka. Enumeration of immune cells in blood and melanomacrophages in the liver, assay of serum and hepatic cytokines, and Th1/Th2 cytokine polarisation were investigated. Immune cell counts indicated overall immunosuppression with decreasing total WBC and splenocyte counts while neutrophil/lymphocyte ratio increased with metal exposure, indicating metal mediated stress. Serum IL6 levels of metal exposed frogs reported the highest (~ 9360 pg/mL) of all cytokines tested. Significantly elevated IFNγ production (P < 0.05) was evident in heavy metal exposed frogs. Th1/Th2 cytokine ratio in both serum and liver tissue homogenates was Th1 skewed due to significantly higher production of pro-inflammatory cytokines, IFNγ in serum and TNFα in the liver (P < 0.01).Metal mediated aggregations of melanomacrophages in the liver were positively and significantly (P < 0.05) correlated with the hepatic expression of TNFα, IL6 and IL10 activity. Overall, Th1 skewed response may well be due to oxidative stress mediated nuclear factor κ-light chain enhancer of activated B cells (NFκB) which enhances the transcription of pro-inflammatory cytokines. Xenobiotic stress has recently imposed an unprecedented level of threat to wildlife, particularly to sensitive species such as amphibians. Therefore, understanding the interactions between physiological stress and related immune responses is fundamental to conserve these environmental sentinels in the face of emerging eco

  19. Heavy metal mediated innate immune responses of the Indian green frog, Euphlyctis hexadactylus (Anura: Ranidae): Cellular profiles and associated Th1 skewed cytokine response

    Energy Technology Data Exchange (ETDEWEB)

    Jayawardena, Uthpala A.; Ratnasooriya, Wanigasekara D.; Wickramasinghe, Deepthi D.; Udagama, Preethi V., E-mail: dappvr@yahoo.com

    2016-10-01

    Immune cell and cytokine profiles in relation to metal exposure though much studied in mammals has not been adequately investigated in amphibians, due mainly to lack of suitable reagents for cytokine profiling in non-model species. However, interspecies cross reactivity of cytokines permitted us to assay levels of IFNγ, TNFα, IL6 and IL10in a common anuran, the Indian green frog (Euphlyctis hexadactylus), exposed to heavy metals (Cd, Cr, Cu, Zn and Pb, at ~ 5 ppm each) under field and laboratory settings in Sri Lanka. Enumeration of immune cells in blood and melanomacrophages in the liver, assay of serum and hepatic cytokines, and Th1/Th2 cytokine polarisation were investigated. Immune cell counts indicated overall immunosuppression with decreasing total WBC and splenocyte counts while neutrophil/lymphocyte ratio increased with metal exposure, indicating metal mediated stress. Serum IL6 levels of metal exposed frogs reported the highest (~ 9360 pg/mL) of all cytokines tested. Significantly elevated IFNγ production (P < 0.05) was evident in heavy metal exposed frogs. Th1/Th2 cytokine ratio in both serum and liver tissue homogenates was Th1 skewed due to significantly higher production of pro-inflammatory cytokines, IFNγ in serum and TNFα in the liver (P < 0.01).Metal mediated aggregations of melanomacrophages in the liver were positively and significantly (P < 0.05) correlated with the hepatic expression of TNFα, IL6 and IL10 activity. Overall, Th1 skewed response may well be due to oxidative stress mediated nuclear factor κ-light chain enhancer of activated B cells (NFκB) which enhances the transcription of pro-inflammatory cytokines. Xenobiotic stress has recently imposed an unprecedented level of threat to wildlife, particularly to sensitive species such as amphibians. Therefore, understanding the interactions between physiological stress and related immune responses is fundamental to conserve these environmental sentinels in the face of emerging eco

  20. The importance of resolution on the response of mid-latitude transients to enhanced CO2

    International Nuclear Information System (INIS)

    Senior, C.A.

    1994-01-01

    The impact of global warming on the activity of the mid-latitude transients is not well understood. Work with simple models suggests that there will be two competing effects on transient activity. Firstly, there will be a reduction in the baroclinicity due to a smaller pole-equator temperature gradient and secondly there will be increased moisture availability in a warmer atmosphere. A comparison of the mid-latitude transients from two versions of the Hadley Centre for Climate Prediction and Research GCM run at different resolutions is presented and the importance of resolution on the simulation of the high and low frequency variability is discussed. At higher resolution, one of the largest responses of the model to a doubling of atmospheric CO 2 is an enhancement of the westerly flow in the North Atlantic, but this is much reduced at lower resolution. Consistency is sort between changes in the time mean flow and the transient behavior

  1. Allele-specific cytokine responses at the HLA-C locus, implications for psoriasis

    Science.gov (United States)

    Hundhausen, Christian; Bertoni, Anna; Mak, Rose K; Botti, Elisabetta; Di Meglio, Paola; Clop, Alex; Laggner, Ute; Chimenti, Sergio; Hayday, Adrian C; Barker, Jonathan N; Trembath, Richard C; Capon, Francesca; Nestle, Frank O

    2011-01-01

    Psoriasis is an inflammatory skin disorder that is inherited as a complex trait. Genetic studies have repeatedly highlighted HLA-C as the major determinant for psoriasis susceptibility, with the Cw*0602 allele conferring significant disease risk in a wide-range of populations. Despite the potential importance of HLA-C variation in psoriasis, either via an effect on peptide presentation or immuno-inhibitory activity, allele-specific expression patterns have not been investigated. Here, we used reporter assays to characterize two regulatory variants, which virtually abolished the response to TNF-α (rs2524094) and IFN-γ (rs10657191) in HLA-Cw*0602 and a cluster of related alleles. We validated these findings through the analysis of HLA-Cw*0602 expression in primary keratinocytes treated with TNF-α and IFN-γ. Finally, we showed that HLA-Cw*0602 transcripts are not increased in psoriatic skin lesions, despite highly elevated TNF-α levels. Thus, our findings demonstrate the presence of allele-specific differences in HLA-C expression and indicate that HLA-Cw*0602 is unresponsive to up-regulation by key pro-inflammatory cytokines in psoriasis. These data pave the way for functional studies into the pathogenic role of the major psoriasis susceptibility allele. PMID:22113476

  2. Allele-specific cytokine responses at the HLA-C locus: implications for psoriasis.

    Science.gov (United States)

    Hundhausen, Christian; Bertoni, Anna; Mak, Rose K; Botti, Elisabetta; Di Meglio, Paola; Clop, Alex; Laggner, Ute; Chimenti, Sergio; Hayday, Adrian C; Barker, Jonathan N; Trembath, Richard C; Capon, Francesca; Nestle, Frank O

    2012-03-01

    Psoriasis is an inflammatory skin disorder that is inherited as a complex trait. Genetic studies have repeatedly highlighted HLA-C as the major determinant for psoriasis susceptibility, with the Cw*0602 allele conferring significant disease risk in a wide range of populations. Despite the potential importance of HLA-C variation in psoriasis, either via an effect on peptide presentation or immuno-inhibitory activity, allele-specific expression patterns have not been investigated. Here, we used reporter assays to characterize two regulatory variants, which virtually abolished the response to tumor necrosis factor (TNF)-α (rs2524094) and IFN-γ (rs10657191) in HLA-Cw*0602 and a cluster of related alleles. We validated these findings through the analysis of HLA-Cw*0602 expression in primary keratinocytes treated with TNF-α and IFN-γ. Finally, we showed that HLA-Cw*0602 transcripts are not increased in psoriatic skin lesions, despite highly elevated TNF-α levels. Thus, our findings demonstrate the presence of allele-specific differences in HLA-C expression and indicate that HLA-Cw*0602 is unresponsive to upregulation by key proinflammatory cytokines in psoriasis. These data pave the way for functional studies into the pathogenic role of the major psoriasis susceptibility allele.

  3. Association between cytokine response, the LRINEC score and outcome in patients with necrotising soft tissue infection

    DEFF Research Database (Denmark)

    Hansen, Marco Bo; Rasmussen, Lars Simon; Svensson, Mattias

    2017-01-01

    Early assessment of necrotising soft tissue infection (NSTI) is challenging. Analysis of inflammatory markers could provide important information about disease severity and guide decision making. For this purpose, we investigated the association between cytokine levels and the Laboratory Risk...

  4. Tissue specific distribution of iNKT cells impacts their cytokine response

    OpenAIRE

    Lee, You Jeong; Wang, Haiguang; Starrett, Gabriel J.; Phuong, Vanessa; Jameson, Stephen C.; Hogquist, Kristin A.

    2015-01-01

    Three subsets of invariant natural killer T (iNKT) cells have been identified, NKT1, NKT2 and NKT17, which produce distinct cytokines when stimulated, but little is known about their localization. Here, we have defined the anatomic localization and systemic distribution of these subsets and measured their cytokine production. Thymic NKT2 cells that produced interleukin-4 (IL-4) at steady state were located in the medulla and conditioned medullary thymocytes. NKT2 cells were abundant in the me...

  5. High-speed LWR transients simulation for optimizing emergency response

    International Nuclear Information System (INIS)

    Wulff, W.; Cheng, H.S.; Lekach, S.V.; Mallen, A.N.; Stritar, A.

    1984-01-01

    The purpose of computer-assisted emergency response in nuclear power plants, and the requirements for achieving such a response, are presented. An important requirement is the attainment of realistic high-speed plant simulations at the reactor site. Currently pursued development programs for plant simulations are reviewed. Five modeling principles are established and a criterion is presented for selecting numerical procedures and efficient computer hardware to achieve high-speed simulations. A newly developed technology for high-speed power plant simulation is described and results are presented. It is shown that simulation speeds ten times greater than real-time process-speeds are possible, and that plant instrumentation can be made part of the computational loop in a small, on-site minicomputer. Additional technical issues are presented which must still be resolved before the newly developed technology can be implemented in a nuclear power plant

  6. Transient response of self-powered neutron detectors

    International Nuclear Information System (INIS)

    Boeck, H.; Gebureck, P.; Stegemann, D.

    The behaviour of self-powered neutron detectors with Co, Er, Hf and Pt emitters was investigated during reactor square wave and pulse operation. The detector's response was compared with the current of an excore ionization chamber. Characteristical deviations from linearity were observed with all detectors at fast reactor periods. The exact cause of these deviations is not yet fully understood but several possibilities for the nonlinear behaviour of self-powered neutron detectors are outlined. (author)

  7. Forced expression of stabilized c-Fos in dendritic cells reduces cytokine production and immune responses in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Yoshida, Ryoko; Suzuki, Mayu; Sakaguchi, Ryota; Hasegawa, Eiichi; Kimura, Akihiro; Shichita, Takashi; Sekiya, Takashi [Department of Microbiology and Immunology, Keio University School of Medicine, 35 Shinanomachi, Shinjyuku-ku, Tokyo 160-8582 (Japan); Japan Science and Technology Agency, CREST, Chiyoda-ku 102-0075 (Japan); Shiraishi, Hiroshi [Division of Medical Biochemistry, Department of Biomolecular Sciences, Saga Medical School, Saga (Japan); Shimoda, Kouji [Department of Laboratory Animal Center, Keio University School of Medicine, Tokyo (Japan); Yoshimura, Akihiko, E-mail: yoshimura@a6.keio.jp [Department of Microbiology and Immunology, Keio University School of Medicine, 35 Shinanomachi, Shinjyuku-ku, Tokyo 160-8582 (Japan); Japan Science and Technology Agency, CREST, Chiyoda-ku 102-0075 (Japan)

    2012-06-29

    Highlights: Black-Right-Pointing-Pointer Dendritic cells expressing stabilized c-Fos produced less inflammatory cytokines. Black-Right-Pointing-Pointer Dendritic cells expressing stabilized c-Fos activated T cells less efficiently. Black-Right-Pointing-Pointer Transgenic mice expressing stabilized c-Fos were resistant to EAE model. -- Abstract: Intracellular cyclic adenosine monophosphate (cAMP) suppresses innate immunity by inhibiting proinflammatory cytokine production by monocytic cells. We have shown that the transcription factor c-Fos is responsible for cAMP-mediated suppression of inflammatory cytokine production, and that c-Fos protein is stabilized by IKK{beta}-mediated phosphorylation. We found that S308 is one of the major phosphorylation sites, and that the S308D mutation prolongs c-Fos halflife. To investigate the role of stabilized c-Fos protein in dendritic cells (DCs) in vivo, we generated CD11c-promoter-deriven c-FosS308D transgenic mice. As expected, bone marrow-derived DCs (BMDCs) from these Tg mice produced smaller amounts of inflammatory cytokines, including TNF-{alpha}, IL-12, and IL-23, but higher levels of IL-10, in response to LPS, than those from wild-type (Wt) mice. When T cells were co-cultured with BMDCs from Tg mice, production of Th1 and Th17 cytokines was reduced, although T cell proliferation was not affected. Tg mice demonstrated more resistance to experimental autoimmune encephalomyelitis (EAE) than did Wt mice. These data suggest that c-Fos in DCs plays a suppressive role in certain innate and adaptive immune responses.

  8. Pro-inflammatory Cytokine Response and Genetic Diversity in Merozoite Surface Protein 2 of Plasmodium falciparum Isolates from Nigeria.

    Science.gov (United States)

    Ajibaye, Olusola; Osuntoki, Akinniyi A; Ebuehi, Albert Ot; Iwalokun, Bamidele A; Balogun, Emmanuel O; Egbuna, Kathleen N

    2017-01-01

    Polymorphisms in Plasmodium falciparum merozoite surface protein-2 ( msp -2) and associated parasite genetic diversity which varies between malaria-endemic regions remain a limitation in malaria vaccine development. Pro-inflammatory cytokines are important in immunity against malaria, understanding the influence of genetic diversity on cytokine response is important for effective vaccine design. P. falciparum isolates obtained from 300 Nigerians with uncomplicated falciparum malaria at Ijede General Hospital, Ijede (IJE), General Hospital Ajeromi, Ajeromi (AJE) and Saint Kizito Mission Hospital, Lekki, were genotyped by nested polymerase chain reaction of msp -2 block 3 while ELISA was used to determine the pro-inflammatory cytokine response to describe the genetic diversity of P. falciparum . Eighteen alleles were observed for msp -2 loci. Of the 195 isolates, 61 (31.0%) had only FC27-type alleles, 38 (19.7%) had only 3D7-type alleles, and 49.3% had multiple parasite lines with both alleles. Band sizes were 275-625 bp for FC27 and 150-425 bp for 3D7. Four alleles were observed from LEK, 2 (375-425 bp) and 2 (275-325 bp) of FC27-and 3D7-types, respectively; 12 alleles from AJE, 9 (275-625 bp) and 3 (325-425 bp) of FC27-types and 3D7-types, respectively; while IJE had a total of 12 alleles, 9 (275-625 bp) and 3 (325-425 bp) of FC27-types and 3D7-types, respectively. Mean multiplicity of infection (MOI) was 1.54. Heterozygosity ( H E ) ranged from 0.77 to 0.87 and was highest for IJE (0.87). Cytokine response was higher among 0.05) but with neither parasite density nor infection type. P. falciparum genetic diversity is extensive in Nigeria, protection via pro-inflammatory cytokines have little or no interplay with infection multiplicity.

  9. Transient Response Dynamic Module Modifications to Include Static and Kinetic Friction Effects

    Science.gov (United States)

    Misel, J. E.; Nenno, S. B.; Takahashi, D.

    1984-01-01

    A methodology that supports forced transient response dynamic solutions when both static and kinetic friction effects are included in a structural system model is described. Modifications that support this type of nonlinear transient response solution are summarized for the transient response dynamics (TRD) NASTRAN module. An overview of specific modifications for the NASTRAN processing subroutines, INITL, TRD1C, and TRD1D, are described with further details regarding inspection of nonlinear input definitions to define the type of nonlinear solution required, along with additional initialization requirements and specific calculation subroutines to successfully solve the transient response problem. The extension of the basic NASTRAN nonlinear methodology is presented through several stages of development to the point where constraint equations and residual flexibility effects are introduced into the finite difference Newmark-Beta recurrsion formulas. Particular emphasis is placed on cost effective solutions for large finite element models such as the Space Shuttle with friction degrees of freedom between the orbiter and payloads mounted in the cargo bay. An alteration to the dynamic finite difference equations of motion is discussed, which allows one to include friction effects at reasonable cost for large structural systems such as the Space Shuttle. Data are presented to indicate the possible impact of transient friction loads to the payload designer for the Space Shuttle. Transient response solution data are also included, which compare solutions without friction forces and those with friction forces for payloads mounted in the Space Shuttle cargo bay. These data indicate that payload components can be sensitive to friction induced loads.

  10. Comparison of cytokine immune responses to Brucella abortus and Yersinia enterocolitica serotype O:9 infections in BALB/c mice.

    Science.gov (United States)

    Gu, Wenpeng; Wang, Xin; Qiu, Haiyan; Cui, Buyun; Zhao, Shiwen; Zheng, Han; Xiao, Yuchun; Liang, Junrong; Duan, Ran; Jing, Huaiqi

    2013-12-01

    Brucella abortus and Yersinia enterocolitica serotype O:9 serologically cross-react in the immune response with the host; therefore, our aim was to compare the immune responses to these two pathogens. We selected typical B. abortus and Y. enterocolitica O:9 strains to study the cytokine immune response and the histopathological changes in livers and spleens of BALB/c mice. The data showed the cytokine responses to the two strains of pathogens were different, where the average levels of granulocyte-macrophage colony-stimulating factor (GM-CSF), gamma interferon (IFN-γ), interleukin-12 (IL-12), and tumor necrosis factor alpha (TNF-α) were higher with B. abortus infections than with Y. enterocolitica O:9 infections, especially for IFN-γ, while the IL-10 level was lower and the levels of IL-1β, IL-4, IL-5, and IL-6 were similar. The histopathological effects in the livers and spleens of the BALB/c mice with B. abortus and Y. enterocolitica O:9 infections were similar; however, the pathological changes in the liver were greater with B. abortus infections, while damage in the spleen was greater with Y. enterocolitica O:9 infections. These observations show that different cytokine responses and histopathological changes occur with B. abortus and Y. enterocolitica O:9 infections.

  11. Energy balance and transient responses in wave driven plasmas

    International Nuclear Information System (INIS)

    Rax, J.M.

    1987-06-01

    In a current-drive experiment with a RF power source, a certain amount of power is absorbed by resonant electrons. From the electrons, energy can flow through four channels: it can be converted into magnetic work when the electron interacts with an electric field, or it can be converted into heat when the electron collides the thermal plasma. In addition, there exists also the conversion of the low frequency RF energy into high frequency non thermal free-free or cyclotron radiation. Efficiencies of these conversions are considered together with the turn-on times of the associated responses

  12. A neural model for transient identification in dynamic processes with 'don't know' response

    International Nuclear Information System (INIS)

    Mol, Antonio C. de A.; Martinez, Aquilino S.; Schirru, Roberto

    2003-01-01

    This work presents an approach for neural network based transient identification which allows either dynamic identification or a 'don't know' response. The approach uses two 'jump' multilayer neural networks (NN) trained with the backpropagation algorithm. The 'jump' network is used because it is useful to dealing with very complex patterns, which is the case of the space of the state variables during some abnormal events. The first one is responsible for the dynamic identification. This NN uses, as input, a short set (in a moving time window) of recent measurements of each variable avoiding the necessity of using starting events. The other one is used to validate the instantaneous identification (from the first net) through the validation of each variable. This net is responsible for allowing the system to provide a 'don't know' response. In order to validate the method, a Nuclear Power Plant (NPP) transient identification problem comprising 15 postulated accidents, simulated for a pressurized water reactor (PWR), was proposed in the validation process it has been considered noisy data in order to evaluate the method robustness. Obtained results reveal the ability of the method in dealing with both dynamic identification of transients and correct 'don't know' response. Another important point studied in this work is that the system has shown to be independent of a trigger signal which indicates the beginning of the transient, thus making it robust in relation to this limitation

  13. Benzodiazepine temazepam suppresses the transient auditory 40-Hz response amplitude in humans.

    Science.gov (United States)

    Jääskeläinen, I P; Hirvonen, J; Saher, M; Pekkonen, E; Sillanaukee, P; Näätänen, R; Tiitinen, H

    1999-06-18

    To discern the role of the GABA(A) receptors in the generation and attentive modulation of the transient auditory 40-Hz response, the effects of the benzodiazepine temazepam (10 mg) were studied in 10 healthy social drinkers, using a double-blind placebo-controlled design. Three hundred Hertz standard and 330 Hz rare deviant tones were presented to the left, and 1000 Hz standards and 1100 Hz deviants to the right ear of the subjects. Subjects attended to a designated ear and were to detect deviants therein while ignoring tones to the other. Temazepam significantly suppressed the amplitude of the 40-Hz response, the effect being equal for attended and non-attended tone responses. This suggests involvement of GABA(A) receptors in transient auditory 40-Hz response generation, however, not in the attentive modulation of the 40-Hz response.

  14. Characterization of main cytokine sources from the innate and adaptive immune responses following primary 17DD yellow fever vaccination in adults.

    Science.gov (United States)

    Silva, Maria Luiza; Martins, Marina Angela; Espírito-Santo, Luçandra Ramos; Campi-Azevedo, Ana Carolina; Silveira-Lemos, Denise; Ribeiro, José Geraldo Leite; Homma, Akira; Kroon, Erna Geessien; Teixeira-Carvalho, Andréa; Elói-Santos, Silvana Maria; Martins-Filho, Olindo Assis

    2011-01-10

    The mechanisms of immune response following yellow fever (YF-17DD) vaccination are still poorly understood. In this study, we have performed a longitudinal investigation (days 0, 7, 15 and 30) to characterize the cytokine profile of innate and adaptive immunity following YF-17DD first-time vaccination. Data from non-stimulated cultures demonstrated a prominent participation of the innate immunity with increased frequency of TNF-α(+) neutrophils and IFN-γ(+) NK-cells at day 7 besides TNF-α(+) monocytes at day 7, day 15 and day 30. Increased frequency of IL-10(+) monocytes was observed at day 15 and day 30, and decreased percentage of IL-4(+) NK-cells were detected at day 7, day 15 and day 30. Time-dependent and oscillating cytokine pattern was observed in CD4(+) T-cells, with low percentage of IL-12(+), IL-4(+) and IL-10(+) cells at day 7 and increased frequency of TNF-α(+) cells at day 15 besides IFN-γ(+) and IL-5(+) cells at day 15 and day 30. Later changes with increased percentage of IL-12(+) and IL-5(+)CD8(+) T-cells were observed at day 30. Increased frequency of IL-10(+) B-cells was observed at day 15, when seroconversion was detected in all vaccinees. The overall cytokine analysis of non-stimulated leukocytes showed a transient shift towards a pro-inflammatory profile at day 7, mainly due to changes in the innate immunity, which draws back toward a mixed/regulatory pattern at day 15 and day 30. The changes induced by the in vitro YF-17DD vaccine-stimulation were mainly observed at day 0 and day 7 (before seroconversion) with minor changes at day 15 and day 30 (after seroconversion). These data support the hypothesis that a complex network with mixed pro/anti-inflammatory cytokine profile is associated with the establishment of the protective immunity following YF-17DD primo-vaccination, free of adverse events. Copyright © 2010 Elsevier Ltd. All rights reserved.

  15. Cytokines in the host response to Candida vaginitis: Identifying a role for non-classical immune mediators, S100 alarmins

    Science.gov (United States)

    Yano, Junko; Noverr, Mairi C.; Fidel, Paul L.

    2011-01-01

    Vulvovaginal candidiasis (VVC), caused by Candida albicans, affects a significant number of women during their reproductive years. More than two decades of research have been focused on the mechanisms associated with susceptibility or resistance to symptomatic infection. Adaptive immunity by Th1-type CD4+ T cells and downstream cytokine responses are considered the predominant host defense mechanisms against mucosal Candida infections. However, numerous clinical and animal studies have indicated no or limited protective role of cells and cytokines of the Th1 or Th2 lineage against vaginal infection. The role for Th17 is only now begun to be investigated in-depth for VVC with results already showing significant controversy. On the other hand, a clinical live-challenge study and an established animal model have shown that a symptomatic condition is intimately associated with the vaginal infiltration of polymorphonuclear leukocytes (PMNs) but with no effect on vaginal fungal burden. Subsequent studies identified S100A8 and S100A9 Alarmins as key chemotactic mediators of the acute PMN response. These chemotactic danger signals appear to be secreted by vaginal epithelial cells upon interaction and early adherence of Candida. Thus, instead of a putative immunodeficiency against Candida involving classical immune cells and cytokines of the adaptive response, the pathological inflammation in VVC is now considered a consequence of a non-productive innate response initiated by non-classical immune mediators. PMID:22182685

  16. Parameters Affecting the Transient Response of an Impacting Beam

    Directory of Open Access Journals (Sweden)

    Weiping Xu

    2013-01-01

    Full Text Available Impact causes shock waves that may be unexpected and damaging. A computationally efficient impact model with a generic beam which is discrete in time and continuous in space was undertaken; an Euler-Bernoulli beam with adjustable boundary conditions and variable contact location is numerically studied under a pulse loading. Experiments on a cantilever beam were carried out to verify the effects of influential parameters. A half-sine pulse excitation was applied through a mechanical shaker, and the deflection was captured by a high speed camera. Numerous test cases were conducted that varied pulse duration, pulse amplitude, and clearance. Decreasing the pulse duration lowers all deflection amplitudes, but the time in contact is insensitive. No gap causes minimal beam response, and increasing gap generates greater deflection. Representative test cases were selected for validating the theoretical model. When comparing numerical simulation with experimental results, satisfactory agreement for amplitude and duration can be reached even with raw input parameters. The contribution of this study is the incorporation of unique pulse loading, changeable boundary conditions, adjustable contact/impact situations, comprehensive parameter studies, and high speed photography.

  17. Expression of IL-23/Th17-related cytokines in basal cell carcinoma and in the response to medical treatments.

    Directory of Open Access Journals (Sweden)

    Cristina Pellegrini

    Full Text Available Several immune-related markers have been implicated in basal cell carcinoma (BCC pathogenesis. The BCC inflammatory infiltrate is dominated by Th2 cytokines, suggesting a specific state of immunosuppression. In contrast, regressing BCC are characterized by a Th1 immune response with IFN-γ promoting a tumor suppressive activity. IL-23/Th17-related cytokines, as interleukin (IL-17, IL-23 and IL-22, play a significant role in cutaneous inflammatory diseases, but their involvement in skin carcinogenesis is controversial and is poorly investigated in BCC. In this study we investigated the expression of IFN-γ, IL-17, IL-23 and IL-22 cytokines in BCC at the protein and mRNA level and their modulation during imiquimod (IMQ treatment or photodynamic therapy (PDT. IFN-γ, IL-17, IL-23 and IL-22 levels were evaluated by immunohistochemistry and quantitative Real Time PCR in 41 histopathologically-proven BCCs (28 superficial and 13 nodular from 39 patients. All BCC samples were analyzed at baseline and 19 of 41 also during medical treatment (9 with IMQ 5% cream and 10 with MAL-PDT. Association between cytokines expression and clinico-pathological variables was evaluated. Higher levels of IFN-γ, IL-17, IL-23 and IL-22 were found in BCCs, mainly in the peritumoral infiltrate, compared to normal skin, with the expression being correlated to the severity of the inflammatory infiltrate. IFN-γ production was higher in superficial BCCs compared to nodular BCCs, while IL-17 was increased in nodular BCCs. A significant correlation was found between IFN-γ and IL-17 expression with both cytokines expressed by CD4+ and CD8+ T-cells. An increase of all cytokines occurred during the inflammatory phase induced by IMQ and at the early time point of PDT treatment, with significant evidence for IFN-γ, IL-23, and IL-22. Our results confirm the role of IFN-γ and support the involvement of IL-23/Th17-related cytokines in BCC pathogenesis and in the inflammatory response

  18. Proceedings of transient thermal-hydraulics and coupled vessel and piping system responses 1991

    International Nuclear Information System (INIS)

    Wang, G.Y.; Shin, Y.W.; Moody, F.J.

    1991-01-01

    This book reports on transient thermal-hydraulics and coupled vessel and piping system responses. Topics covered include: nuclear power plant containment designs; analysis of control rods; gate closure of hydraulic turbines; and shock wave solutions for steam water mixtures in piping systems

  19. Ad Hoc Transient Communities to Enhance Social Interaction and Spread Tutor Responsibilities

    OpenAIRE

    Sloep, Peter; Kester, Liesbeth; Brouns, Francis; Van Rosmalen, Peter; De Vries, Fred; De Croock, Marcel; Koper, Rob

    2007-01-01

    Sloep, P.B., Kester, L. Brouns, F., Van Rosmalen, P., De Vries, F., De Croock, M., Koper, R. (2007) Ad Hoc Transient Communities to Enhance Social Interaction and Spread Tutor Responsibilities. In V. Uskov (Ed.) The Sixth IASTED International Conference on Web-based Education WBE 2007, March 14-16, Chamonix, France (pp. 549-554). Calgary, Canada: Acta Press.

  20. Ad Hoc Transient Communities to Enhance Social Interaction and Spread Tutor Responsibilities

    NARCIS (Netherlands)

    Sloep, Peter; Kester, Liesbeth; Brouns, Francis; Van Rosmalen, Peter; De Vries, Fred; De Croock, Marcel; Koper, Rob

    2007-01-01

    Sloep, P.B., Kester, L. Brouns, F., Van Rosmalen, P., De Vries, F., De Croock, M., Koper, R. (2007) Ad Hoc Transient Communities to Enhance Social Interaction and Spread Tutor Responsibilities. In V. Uskov (Ed.) The Sixth IASTED International Conference on Web-based Education WBE 2007, March 14-16,

  1. Ad Hoc Transient Communities to Enhance Social Interaction and Spread Tutor Responsibilities

    NARCIS (Netherlands)

    Sloep, Peter; Kester, Liesbeth; Brouns, Francis; Van Rosmalen, Peter; De Vries, Fred; De Croock, Marcel; Koper, Rob

    2007-01-01

    Sloep, P.B., Kester, L., Brouns, F., Van Rosmalen, P., De Vries, F., De Croock, M., Koper, R. (2007). Ad Hoc Transient Communities to Enhance Social Interaction and Spread Tutor Responsibilities. Presentation given at the Sixth IASTED International Conference on Web-based Education, 14-16 March,

  2. A Capacitor-Free, Fast Transient Response Linear Voltage Regulator In a 180nm CMOS

    DEFF Research Database (Denmark)

    Deleuran, Alexander N.; Lindbjerg, Nicklas; Pedersen, Martin K.

    2015-01-01

    A 1.8 V capacitor-free linear regulator with fast transient response based on a new topology with a fast and slow regulation loop is presented. The design has been laid out and simulated in a 0.18 µm CMOS process. The design has a low component count and is tailored for system-on-chip integration...

  3. Can short-term administration of dexamethasone abrogate radiation-induced acute cytokine gene response in lung and modify subsequent molecular responses?

    International Nuclear Information System (INIS)

    Hong, J.-H.; Chiang, C.-S.; Tsao, C.-Y.; Lin, P.-Y.; Wu, C.-J.; McBride, William H.

    2001-01-01

    Purpose: To investigate the effects of short-term administration of dexamethasone (DEX) on radiation-induced responses in the mouse lung, focusing on expression of pro-inflammatory cytokine and related genes. Methods and Materials: At indicated times after thoracic irradiation and/or drug treatment, mRNA expression levels of cytokines (mTNF-α, mIL-1α, mIL-1β, mIL-2, mIL-3, mIL-4, mIL-5, mIL-6, mIFN-γ) and related genes in the lungs of C3H/HeN mice were measured by RNase protection assay. Results: Radiation-induced pro-inflammatory cytokine mRNA expression levels in lung peak at 6 h after thoracic irradiation. DEX (5 mg/kg) suppresses both basal cytokine mRNA levels and this early response when given immediately after irradiation. However, by 24 h, in mice treated with DEX alone or DEX plus radiation, there was a strong rebound effect that lasted up to 3 days. Modification of the early radiation-induced response by DEX did not change the second wave of cytokine gene expression in the lung that occurs at 1 to 2 weeks, suggesting that early cytokine gene induction might not determine subsequent molecular events. A single dose of DEX attenuated, but did not completely suppress, increases in cytokine mRNA levels induced by lipopolysaccharide (2.5 mg/kg) treatment, but, unlike with radiation, no significant rebound effect was seen. Five days of dexamethasone treatment in the pneumonitic phase also inhibited pro-inflammatory cytokine gene expression and, again, there was a rebound effect after withdrawal of the drug. Conclusions: Our findings suggest that short-term use of dexamethasone can temporarily suppress radiation-induced pro-inflammatory cytokine gene expression, but there may be a rebound after drug withdrawal and the drug does little to change the essence and course of the pneumonitic process

  4. Cytokines as a predictor of clinical response following hip arthroscopy: minimum 2-year follow-up.

    Science.gov (United States)

    Shapiro, Lauren M; Safran, Marc R; Maloney, William J; Goodman, Stuart B; Huddleston, James I; Bellino, Michael J; Scuderi, Gaetano J; Abrams, Geoffrey D

    2016-08-01

    Hip arthroscopy in patients with osteoarthritis has been shown to have suboptimal outcomes. Elevated cytokine concentrations in hip synovial fluid have previously been shown to be associated with cartilage pathology. The purpose of this study was to determine whether a relationship exists between hip synovial fluid cytokine concentration and clinical outcomes at a minimum of 2 years following hip arthroscopy. Seventeen patients without radiographic evidence of osteoarthritis had synovial fluid aspirated at time of portal establishment during hip arthroscopy. Analytes included fibronectin-aggrecan complex as well as a multiplex cytokine array. Patients completed the modified Harris Hip Score, Western Ontario and McMaster Universities Arthritis Index and the International Hip Outcomes Tool pre-operatively and at a minimum of 2 years following surgery. Pre and post-operative scores were compared with a paired t-test, and the association between cytokine values and clinical outcome scores was performed with Pearson's correlation coefficient with an alpha value of 0.05 set as significant. Sixteen of seventeen patients completed 2-year follow-up questionnaires (94%). There was a significant increase in pre-operative to post-operative score for each clinical outcome measure. No statistically significant correlation was seen between any of the intra-operative cytokine values and either the 2-year follow-up scores or the change from pre-operative to final follow-up outcome values. No statistically significant associations were seen between hip synovial fluid cytokine concentrations and 2-year follow-up clinical outcome assessment scores for those undergoing hip arthroscopy.

  5. Surge protective device response to steep front transient in low voltage circuit

    Energy Technology Data Exchange (ETDEWEB)

    Marcuz, J.; Binczak, S.; Bilbault, J.M. [Universite de Bourgogne, Dijon (France)], Emails: jerome.marcuz@ laposte.net, stbinc@u-bourgogne.fr, bilbault@u-bourgogne.fr; Girard, F. [ADEE Electronic, Pont de Pany (France)

    2007-07-01

    Surge propagation on cables of electrical or data lines leads to a major protection problem as the number of equipment based on solid-state circuits or microprocessors increases. Sub-microsecond components of real surge waveform has to be taken into account for a proper protection even in the case of surges caused by indirect lightning effects. The response of a model of transient voltage suppressor diode based surge protection device (SPD) to fast front transient is analytically studied, then compared to simulations, including the lines connected to the SPD and to the protected equipment. (author)

  6. Cytokines, Chaperones and Neuroinflammatory Responses in Heroin-Related Death: What Can We Learn from Different Patterns of Cellular Expression?

    Directory of Open Access Journals (Sweden)

    Vittorio Fineschi

    2013-09-01

    Full Text Available Heroin (3,6-diacetylmorphine has various effects on the central nervous system with several neuropathological alterations including hypoxic-ischemic brain damage from respiratory depressing effects and neuroinflammatory response. Both of these mechanisms induce the release of cytokines, chemokines and other inflammatory mediators by the activation of many cell types such as leucocytes and endothelial and glial cells, especially microglia, the predominant immunocompetent cell type within the central nervous system. The aim of this study is to clarify the correlation between intravenous heroin administration in heroin related death and the neuroinflammatory response. We selected 45 cases among autopsies executed for heroin-related death (358 total cases; immunohistochemical studies and Western blotting analyses were used to investigate the expression of brain markers such as tumor necrosis factor-α, oxygen-regulated protein 150, (interleukins IL-1β, IL-6, IL-8, IL-10, IL-15, cyclooxygenase-2, heat shock protein 70, and CD68 (MAC387. Findings demonstrated that morphine induces inflammatory response and cytokine release. In particular, oxygen-regulated protein 150, cyclooxygenase-2, heat shock protein 70, IL-6 and IL-15 cytokines were over-expressed with different patterns of cellular expression.

  7. Placental-mediated increased cytokine response to lipopolysaccharides: a potential mechanism for enhanced inflammation susceptibility of the preterm fetus

    Directory of Open Access Journals (Sweden)

    Ross MG

    2012-07-01

    Full Text Available Julie L Boles,1 Michael G Ross,1 Ron Beloosesky,2 Mina Desai,1 Louiza Belkacemi11Department of Obstetrics and Gynecology, Harbor-UCLA Medical Center, Los Angeles Biomedical Research Institute at Harbor-UCLA, David Geffen School of Medicine at UCLA, University of California, Los Angeles, Torrance, CA, USA; 2Department of Obstetrics and Gynecology, Rambam Medical Center, Haifa, IsraelBackground: Cerebral palsy is a nonprogressive motor impairment syndrome that has no effective cure. The etiology of most cases of cerebral palsy remains unknown; however, recent epidemiologic data have demonstrated an association between fetal neurologic injury and infection/inflammation. Maternal infection/inflammation may be associated with the induction of placental cytokines that could result in increased fetal proinflammatory cytokine exposure, and development of neonatal neurologic injury. Therefore, we sought to explore the mechanism by which maternal infection may produce a placental inflammatory response. We specifically examined rat placental cytokine production and activation of the Toll-like receptor 4 (TLR4 pathway in response to lipopolysaccharide exposure at preterm and near-term gestational ages.Methods: Preterm (e16 or near-term (e20 placental explants from pregnant rats were treated with 0, 1, or 10 µg/mL lipopolysaccharide. Explant integrity was assessed by lactate dehydrogenase assay. Interleukin-6 and tumor necrosis alpha levels were determined using enzyme-linked immunosorbent assay kits. TLR4 and phosphorylated nuclear factor kappa light chain enhancer of activated B cells (NFκB protein expression levels were determined by Western blot analysis.Results: At both e16 and e20, lactate dehydrogenase levels were unchanged by treatment with lipopolysaccharide. After exposure to lipopolysaccharide, the release of interleukin-6 and tumor necrosis alpha from e16 placental explants increased by 4-fold and 8–9-fold, respectively (P < 0.05 versus

  8. Short communication: Cytokine profiles from blood mononuclear cells of dairy cows classified with divergent immune response phenotypes.

    Science.gov (United States)

    Martin, C E; Paibomesai, M A; Emam, S M; Gallienne, J; Hine, B C; Thompson-Crispi, K A; Mallard, B A

    2016-03-01

    Genetic selection for enhanced immune response has been shown to decrease disease occurrence in dairy cattle. Cows can be classified as high (H), average, or low responders based on antibody-mediated immune response (AMIR), predominated by type-2 cytokine production, and cell-mediated immune response (CMIR) through estimated breeding values for these traits. The purpose of this study was to identify in vitro tests that correlate with in vivo immune response phenotyping in dairy cattle. Blood mononuclear cells (BMC) isolated from cows classified as H-AMIR and H-CMIR through estimated breeding values for immune response traits were stimulated with concanavalin A (ConA; Sigma Aldrich, St. Louis, MO) and gene expression, cytokine production, and cell proliferation was determined at multiple time points. A repeated measures model, which included the effects of immune response group, parity, and stage of lactation, was used to compare differences between immune response phenotype groups. The H-AMIR cows produced more IL-4 protein than H-CMIR cows at 48 h; however, no difference in gene expression of type-2 transcription factor GATA3 or IL4 was noted. The BMC from H-CMIR cows had increased production of IFN-γ protein at 48, 72, and 96 h compared with H-AMIR animals. Further, H-CMIR cows had increased expression of the IFNG gene at 16, 24, and 48 h post-treatment with ConA, although expression of the type-1 transcription factor gene TBX21 did not differ between immune response groups. Although proliferation of BMC increased from 24 to 72 h after ConA stimulation, no differences were found between the immune response groups. Overall, stimulation of H-AMIR and H-CMIR bovine BMC with ConA resulted in distinct cytokine production profiles according to genetically defined groups. These distinct cytokine profiles could be used to define disease resistance phenotypes in dairy cows according to stimulation in vitro; however, other immune response phenotypes should be assessed

  9. Longitudinal monitoring of bottlenose dolphin leukocyte cytokine mRNA responsiveness by qPCR

    Science.gov (United States)

    Both veterinarians caring for bottlenose dolphins (Tursiops truncatus) in managed populations and researchers monitoring wild populations use blood-based diagnostics to monitor bottlenose dolphin health. Quantitative PCR (qPCR) can be used to assess cytokine expression patterns of peripheral blood m...

  10. Induction of Chemokine Secretion and Monocyte Migration by Human Choroidal Melanocytes in Response to Proinflammatory Cytokines

    DEFF Research Database (Denmark)

    Jehs, Tina; Faber, Carsten; Udsen, Maja S.

    2016-01-01

    of 10 HCM donors induced a high initial level of monocyte migration, which decreased upon stimulation with either TCM or IFN-γ and TNF-α. The supernatants from three HCM donors initially showed a low level of monocyte attraction, which increased after exposure to proinflammatory cytokines. Direct...

  11. Inflammatory cytokine response and reduced heart rate variability in newborns with hypoxic-ischemic encephalopathy.

    Science.gov (United States)

    Al-Shargabi, T; Govindan, R B; Dave, R; Metzler, M; Wang, Y; du Plessis, A; Massaro, A N

    2017-06-01

    To determine whether systemic inflammation-modulating cytokine expression is related to heart rate variability (HRV) in newborns with hypoxic-ischemic encephalopathy (HIE). The data from 30 newborns with HIE were analyzed. Cytokine levels (IL-2, IL-4, IL-6, IL-8, IL-10, IL-13, IL-1β, TNF-α, IFN-λ) were measured either at 24 h of cooling (n=5), 72 h of cooling (n=4) or at both timepoints (n=21). The following HRV metrics were quantified in the time domain: alpha_S, alpha_L, root mean square (RMS) at short time scales (RMS_S), RMS at long time scales (RMS_L), while low-frequency power (LF) and high-frequency power (HF) were quantified in the frequency domain. The relationships between HRV metrics and cytokines were evaluated using mixed-models. IL-6, IL-8, IL-10, and IL-13 levels were inversely related to selected HRV metrics. Inflammation-modulating cytokines may be important mediators in the autonomic dysfunction observed in newborns with HIE.

  12. Both very low- and very high in vitro cytokine responses were associated with infant death in low-birth-weight children from Guinea bissau

    DEFF Research Database (Denmark)

    Andersen, Andreas; Jensen, Kristoffer J; Erikstrup, Christian

    2014-01-01

    with lipopolysaccharide (LPS), phytohaemagglutinin (PHA), or purified protein derivative (PPD). The outcome was mortality between bleeding and 1 year of age. Non-linear associations between cytokine responses and mortality were examined. RESULTS: Cytokine measurements were available from 390 children. The mortality rate...... (MR) was high (6.8/100 person-years-observation (PYO)). Both low and high cytokine responses to LPS and PHA were associated with high mortality (MR up to 25/100 PYO in the lowest 10% and 9.2/100 PYO in the highest 10%). In BCG-vaccinated children, higher IFN-γ responses to PPD were associated...

  13. Susceptibility to Lower Respiratory Infections in Childhood is Associated with Perturbation of the Cytokine Response to Pathogenic Airway Bacteria.

    Science.gov (United States)

    Vissing, Nadja Hawwa; Larsen, Jeppe Madura; Rasmussen, Morten Arendt; Chawes, Bo Lund Krogsgaard; Thysen, Anna Hammerich; Bønnelykke, Klaus; Brix, Susanne; Bisgaard, Hans

    2016-05-01

    Neonatal colonization of the airways with respiratory pathogens is associated with increased risk of lower respiratory infections (LRI) in early childhood. Therefore, we hypothesized that children developing LRI have an aberrant immune response to pathogenic bacteria in infancy. The objective was to characterize in vitro the early life systemic immune response to pathogenic bacteria and study the possible association with incidence of LRI during the first 3 years of life. The Copenhagen Prospective Studies on Asthma in Childhood2000 (COPSAC2000) is a clinical birth cohort study of 411 children born of mothers with asthma. LRI incidence was prospectively captured from 6-monthly planned visits and visits at acute respiratory episodes. The in vitro systemic immune response to Haemophilus influenzae, Moraxella catarrhalis and Streptococcus pneumoniae was characterized by the production of TNF-α, IFN-γ, IL-2, IL-5, IL-10, IL-13 and IL-17 in peripheral blood mononuclear cells isolated at age 6 months from 291 infants. Data were analyzed by Poisson regression against incidence of LRI in infancy. A multivariable model including all cytokine responses from the 3 different bacterial stimulations significantly identified children at risk of LRI (P = 0.006). The immune response pattern associated with LRI was characterized by perturbed production of several cytokines rather than production of one specific cytokine, and was independent of concurrent asthma. TNF-α and IL-5 were key drivers but did not explain the entire variation in LRI susceptibility. Children at risk of future LRI present a perturbed systemic immune response upon exposure to common airway pathogens in early life.

  14. Factor XI Deficiency Alters the Cytokine Response and Activation of Contact Proteases during Polymicrobial Sepsis in Mice.

    Directory of Open Access Journals (Sweden)

    Charles E Bane

    Full Text Available Sepsis, a systemic inflammatory response to infection, is often accompanied by abnormalities of blood coagulation. Prior work with a mouse model of sepsis induced by cecal ligation and puncture (CLP suggested that the protease factor XIa contributed to disseminated intravascular coagulation (DIC and to the cytokine response during sepsis. We investigated the importance of factor XI to cytokine and coagulation responses during the first 24 hours after CLP. Compared to wild type littermates, factor XI-deficient (FXI-/- mice had a survival advantage after CLP, with smaller increases in plasma levels of TNF-α and IL-10 and delayed IL-1β and IL-6 responses. Plasma levels of serum amyloid P, an acute phase protein, were increased in wild type mice 24 hours post-CLP, but not in FXI-/- mice, supporting the impression of a reduced inflammatory response in the absence of factor XI. Surprisingly, there was little evidence of DIC in mice of either genotype. Plasma levels of the contact factors factor XII and prekallikrein were reduced in WT mice after CLP, consistent with induction of contact activation. However, factor XII and PK levels were not reduced in FXI-/- animals, indicating factor XI deficiency blunted contact activation. Intravenous infusion of polyphosphate into WT mice also induced changes in factor XII, but had much less effect in FXI deficient mice. In vitro analysis revealed that factor XIa activates factor XII, and that this reaction is enhanced by polyanions such polyphosphate and nucleic acids. These data suggest that factor XI deficiency confers a survival advantage in the CLP sepsis model by altering the cytokine response to infection and blunting activation of the contact (kallikrein-kinin system. The findings support the hypothesis that factor XI functions as a bidirectional interface between contact activation and thrombin generation, allowing the two processes to influence each other.

  15. Cardiorespiratory control and cytokine profile in response to heat stress, hypoxia, and lipopolysaccharide (LPS) exposure during early neonatal period.

    Science.gov (United States)

    McDonald, Fiona B; Chandrasekharan, Kumaran; Wilson, Richard J A; Hasan, Shabih U

    2016-02-01

    Sudden infant death syndrome (SIDS) is one of the most common causes of postneonatal infant mortality in the developed world. An insufficient cardiorespiratory response to multiple environmental stressors (such as prone sleeping positioning, overwrapping, and infection), during a critical period of development in a vulnerable infant, may result in SIDS. However, the effect of multiple risk factors on cardiorespiratory responses has rarely been tested experimentally. Therefore, this study aimed to quantify the independent and possible interactive effects of infection, hyperthermia, and hypoxia on cardiorespiratory control in rats during the neonatal period. We hypothesized that lipopolysaccharide (LPS) administration will negatively impact cardiorespiratory responses to increased ambient temperature and hypoxia in neonatal rats. Sprague-Dawley neonatal rat pups were studied at postnatal day 6-8. Rats were examined at an ambient temperature of 33°C or 38°C. Within each group, rats were allocated to control, saline, or LPS (200 μg/kg) treatments. Cardiorespiratory and thermal responses were recorded and analyzed before, during, and after a hypoxic exposure (10% O2). Serum samples were taken at the end of each experiment to measure cytokine concentrations. LPS significantly increased cytokine concentrations (such as TNFα, IL-1β, MCP-1, and IL-10) compared to control. Our results do not support a three-way interaction between experimental factors on cardiorespiratory control. However, independently, heat stress decreased minute ventilation during normoxia and increased the hypoxic ventilatory response. Furthermore, LPS decreased hypoxia-induced tachycardia. Herein, we provide an extensive serum cytokine profile under various experimental conditions and new evidence that neonatal cardiorespiratory responses are adversely affected by dual interactions of environmental stress factors. © 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on

  16. Immunotoxicity of aflatoxin B1: Impairment of the cell-mediated response to vaccine antigen and modulation of cytokine expression

    International Nuclear Information System (INIS)

    Meissonnier, Guylaine M.; Pinton, Philippe; Laffitte, Joelle; Cossalter, Anne-Marie; Gong, Yun Yun; Wild, Christopher P.; Bertin, Gerard; Galtier, Pierre; Oswald, Isabelle P.

    2008-01-01

    Aflatoxin B1 (AFB1), a mycotoxin produced by Aspergillus flavus or A. parasiticus, is a frequent contaminant of food and feed. This toxin is hepatotoxic and immunotoxic. The present study analyzed in pigs the influence of AFB1 on humoral and cellular responses, and investigated whether the immunomodulation observed is produced through interference with cytokine expression. For 28 days, pigs were fed a control diet or a diet contaminated with 385, 867 or 1807 μg pure AFB1/kg feed. At days 4 and 15, pigs were vaccinated with ovalbumin. AFB1 exposure, confirmed by an observed dose-response in blood aflatoxin-albumin adduct, had no major effect on humoral immunity as measured by plasma concentrations of total IgA, IgG and IgM and of anti-ovalbumin IgG. Toxin exposure did not impair the mitogenic response of lymphocytes but delayed and decreased their specific proliferation in response to the vaccine antigen, suggesting impaired lymphocyte activation in pigs exposed to AFB1. The expression level of pro-inflammatory (TNF-α, IL-1β, IL-6, IFN-γ) and regulatory (IL-10) cytokines was assessed by real-time PCR in spleen. A significant up-regulation of all 5 cytokines was observed in spleen from pigs exposed to the highest dose of AFB1. In pigs exposed to the medium dose, IL-6 expression was increased and a trend towards increased IFN-γ and IL-10 was observed. In addition we demonstrate that IL-6 impaired in vitro the antigenic- but not the mitogenic-induced proliferation of lymphocytes from control pigs vaccinated with ovalbumin. These results indicate that AFB1 dietary exposure decreases cell-mediated immunity while inducing an inflammatory response. These impairments in the immune response could participate in failure of vaccination protocols and increased susceptibility to infections described in pigs exposed to AFB1

  17. Susceptibility to Lower Respiratory Infections in Childhood is Associated with Perturbation of the Cytokine Response to Pathogenic Airway Bacteria

    DEFF Research Database (Denmark)

    Vissing, Nadja Hawwa; Larsen, Jeppe Madura; Rasmussen, Morten Arendt

    2016-01-01

    of 411 children born of mothers with asthma. LRI incidence was prospectively captured from 6-monthly planned visits and visits at acute respiratory episodes. The in vitro systemic immune response to H. influenzae, M. catarrhalis and S. pneumoniae was characterized by the production of TNF-α, IFN-γ, IL-2......, IL-5, IL-10, IL-13, and IL-17 in peripheral blood mononuclear cells isolated at age 6 months from 291 infants. Data were analyzed by Poisson regression against incidence of LRI in infancy. RESULTS:: A multivariable model including all cytokine responses from the three different bacterial stimulations...

  18. Association of O-Antigen Serotype with the Magnitude of Initial Systemic Cytokine Responses and Persistence in the Urinary Tract.

    Science.gov (United States)

    Horvath, Dennis J; Patel, Ashay S; Mohamed, Ahmad; Storm, Douglas W; Singh, Chandra; Li, Birong; Zhang, Jingwen; Koff, Stephen A; Jayanthi, Venkata R; Mason, Kevin M; Justice, Sheryl S

    2016-01-11

    Urinary tract infection (UTI) is one of the most common ailments requiring both short-term and prophylactic antibiotic therapies. Progression of infection from the bladder to the kidney is associated with more severe clinical symptoms (e.g., fever and vomiting) as well as with dangerous disease sequelae (e.g., renal scaring and sepsis). Host-pathogen interactions that promote bacterial ascent to the kidney are not completely understood. Prior studies indicate that the magnitude of proinflammatory cytokine elicitation in vitro by clinical isolates of uropathogenic Escherichia coli (UPEC) inversely correlates with the severity of clinical disease. Therefore, we hypothesize that the magnitude of initial proinflammatory responses during infection defines the course and severity of disease. Clinical UPEC isolates obtained from patients with a nonfebrile UTI elicited high systemic proinflammatory responses early during experimental UTI in a murine model and were attenuated in bladder and kidney persistence. Conversely, UPEC isolates obtained from patients with febrile UTI elicited low systemic proinflammatory responses early during experimental UTI and exhibited prolonged persistence in the bladder and kidney. Soluble factors in the supernatant from saturated cultures as well as the lipopolysaccharide (LPS) serotype correlated with the magnitude of proinflammatory responses in vitro. Our data suggest that the structure of the O-antigen sugar moiety of the LPS may determine the strength of cytokine induction by epithelial cells. Moreover, the course and severity of disease appear to be the consequence of the magnitude of initial cytokines produced by the bladder epithelium during infection. The specific host-pathogen interactions that determine the extent and course of disease are not completely understood. Our studies demonstrate that modest changes in the magnitude of cytokine production observed using in vitro models of infection translate into significant

  19. Association of O-Antigen Serotype with the Magnitude of Initial Systemic Cytokine Responses and Persistence in the Urinary Tract

    Science.gov (United States)

    Horvath, Dennis J.; Patel, Ashay S.; Mohamed, Ahmad; Storm, Douglas W.; Singh, Chandra; Li, Birong; Zhang, Jingwen; Koff, Stephen A.; Jayanthi, Venkata R.; Mason, Kevin M.

    2016-01-01

    ABSTRACT Urinary tract infection (UTI) is one of the most common ailments requiring both short-term and prophylactic antibiotic therapies. Progression of infection from the bladder to the kidney is associated with more severe clinical symptoms (e.g., fever and vomiting) as well as with dangerous disease sequelae (e.g., renal scaring and sepsis). Host-pathogen interactions that promote bacterial ascent to the kidney are not completely understood. Prior studies indicate that the magnitude of proinflammatory cytokine elicitation in vitro by clinical isolates of uropathogenic Escherichia coli (UPEC) inversely correlates with the severity of clinical disease. Therefore, we hypothesize that the magnitude of initial proinflammatory responses during infection defines the course and severity of disease. Clinical UPEC isolates obtained from patients with a nonfebrile UTI elicited high systemic proinflammatory responses early during experimental UTI in a murine model and were attenuated in bladder and kidney persistence. Conversely, UPEC isolates obtained from patients with febrile UTI elicited low systemic proinflammatory responses early during experimental UTI and exhibited prolonged persistence in the bladder and kidney. Soluble factors in the supernatant from saturated cultures as well as the lipopolysaccharide (LPS) serotype correlated with the magnitude of proinflammatory responses in vitro. Our data suggest that the structure of the O-antigen sugar moiety of the LPS may determine the strength of cytokine induction by epithelial cells. Moreover, the course and severity of disease appear to be the consequence of the magnitude of initial cytokines produced by the bladder epithelium during infection. IMPORTANCE The specific host-pathogen interactions that determine the extent and course of disease are not completely understood. Our studies demonstrate that modest changes in the magnitude of cytokine production observed using in vitro models of infection translate into

  20. Male Seminal Relaxin Contributes to Induction of the Post-mating Cytokine Response in the Female Mouse Uterus

    Directory of Open Access Journals (Sweden)

    Danielle J. Glynn

    2017-06-01

    Full Text Available The hormone relaxin is important in female reproduction for embryo implantation, cardiovascular function, and during labor and lactation. Relaxin is also synthesized in males by organs of the male tract. We hypothesized that relaxin might be one component of seminal plasma responsible for eliciting the female cytokine response induced in the uterus at mating. When recombinant relaxin was injected into the uterus of wild-type (Rln+/+ mice at estrus, it evoked the production of Cxcl1 mRNA and its secreted protein product CXCL1 in four of eight animals. Mating experiments were then conducted using mice with a null mutation in the relaxin gene (Rln−/− mice. qRT-PCR analysis of mRNA expression in wild-type females showed diminished uterine expression of several cytokine and chemokine genes in the absence of male relaxin. Similar differences were also noted comparing Rln−/− and Rln+/+ females mated to wild-type males. Quantification of uterine luminal fluid cytokine content confirmed that male relaxin provokes the production of CXCL10 and CSF3 in Rln+/+ females. Differences were also seen comparing Rln−/− and Rln+/+ females mated with Rln−/− males for CXCL1, CSF3, and CCL5, implying that endogenous relaxin in females might prime the uterus to respond appropriately to seminal fluid at coitus. Finally, pan-leukocyte CD45 mRNA was increased in wild-type matings compared to other combinations, implying that male and female relaxin may trigger leukocyte expansion in the uterus. We conclude that male and/or female relaxin may be important in activating the uterine cytokine/chemokine network required to initiate maternal immune adaptation to pregnancy.

  1. Cytokine response patterns in severe pandemic 2009 H1N1 and seasonal influenza among hospitalized adults.

    Directory of Open Access Journals (Sweden)

    Nelson Lee

    Full Text Available BACKGROUND: Studying cytokine/chemokine responses in severe influenza infections caused by different virus subtypes may improve understanding on pathogenesis. METHODS: Adults hospitalized for laboratory-confirmed seasonal and pandemic 2009 A/H1N1 (pH1N1 influenza were studied. Plasma concentrations of 13 cytokines/chemokines were measured at presentation and then serially, using cytometric-bead-array with flow-cytometry and ELISA. PBMCs from influenza patients were studied for cytokine/chemokine expression using ex-vivo culture (Whole Blood Assay,±PHA/LPS stimulation. Clinical variables were prospectively recorded and analyzed. RESULTS: 63 pH1N1 and 53 seasonal influenza patients were studied. pH1N1 patients were younger (mean±S.D. 42.8±19.2 vs 70.5±16.7 years, and fewer had comorbidities. Respiratory/cardiovascular complications were common in both groups (71.4% vs 81.1%, although severe pneumonia with hypoxemia (54.0% vs 28.3% and ICU admissions (25.4% vs 1.9% were more frequent with pH1N1. Hyperactivation of the proinflammatory cytokines IL-6, CXCL8/IL-8, CCL2/MCP-1 and sTNFR-1 was found in pH1N1 pneumonia (2-15 times normal and in complicated seasonal influenza, but not in milder pH1N1 infections. The adaptive-immunity (Th1/Th17-related CXCL10/IP-10, CXCL9/MIG and IL-17A however, were markedly suppressed in severe pH1N1 pneumonia (2-27 times lower than seasonal influenza; P-values<0.01. This pattern was further confirmed with serial measurements. Hypercytokinemia tended to be sustained in pH1N1 pneumonia, associated with a slower viral clearance [PCR-negativity: day 3-4, 55% vs 85%; day 6-7, 67% vs 100%]. Elevated proinflammatory cytokines, particularly IL-6, predicted ICU admission (adjusted OR 12.6, 95%CI 2.6-61.5, per log(10unit increase; P = 0.002, and correlated with fever, tachypnoea, deoxygenation, and length-of-stay (Spearman's rho, P-values<0.01 in influenza infections. PBMCs in seasonal influenza patients were activated and

  2. Gene Expression Profile of Human Cytokines in Response to B.pseudomallei Infection

    Science.gov (United States)

    2017-04-19

    and tested by serial dilution from 1/10 to 149 1/10,240 with sensitized sheep erythrocytes and the reciprocal of the highest dilution 150 at which...tumor necrosis factor-alpha (TNF-α) from T cells and natural killer (NK) cells. It reduces IL-4 mediated suppression of IFN-γ. IL15 Interleukin 15 Pro...inflammatory cytokine which regulates T and natural killer (NK) cell activation and proliferation. TR-17-135 Distribution Statement A: Approved

  3. Transient response simulation of gas separation membrane module for an atmosphere detritiation system

    International Nuclear Information System (INIS)

    Sugiyama, Takahiko; Tanaka, Masahiro; Munakata, Kenzo; Yamamoto, Ichiro

    2012-01-01

    Transient response of a gas separation membrane module for the atmosphere detritiation system was numerically simulated with a mass transfer model. The module contains thousands of hollow fiber type polyimide membranes. The simulation model took into account permeation of water vapor through the dense layer of the membrane, diffusive transfer through the porous support layer and adsorption/desorption of water vapor into the matrix of the porous layer. The slow responses of the water vapor concentration in the retentate and the permeation rate were well reproduced by the present simulation, and transient changes in a follow fiber membrane were investigated in detail. The inventory and the mean residence time of water vapor at 303 K were estimated for the commercial membrane module (UMS-B2, Ube industries, Ltd.) as 5.7 × 10 −3 mol and 380 s, respectively.

  4. Extraction of diagnostic parameters from the transient response of a porous electro ceramic gas sensor

    International Nuclear Information System (INIS)

    Hossein-Babaei, F.; Orvatinia, M.

    2004-01-01

    A novel concept for the diagnosis of a pure target gas in air is presented. The method employs a resistive gas sensor with a mm-thick highly porous electro ceramic gas sensitive body. The diagnosis is based on the fact that the diffusion time of the target gas through the porous body would depend on its molecular properties. The transient response of the device was analyzed based on a diffusion reaction equation. The solutions of the equation were shown to be of diagnostic merits. Such a device was fabricated by partial sintering of a Zn O body formed by low pressure pressing. The transient responses of the device to methanol, ethanol, poropanol and butanol were recorded. The analytical data, and the diagnostic parameters were resulted as the fitting parameters. Comparison of the parameters obtained with those available from the calibration experiments afforded target gas identification

  5. Analysis of transient pressure response near a horizontal well - a coupled diffusion-deformation approach

    Energy Technology Data Exchange (ETDEWEB)

    Li, Y.; Wong, R. K. C. [Calgary Univ., AB (Canada); Yeung, K. C. [Suncor Energy Inc., Calgary, AB (Canada)

    1998-12-31

    Results of an analysis of transient pressure near a horizontal well using a coupled diffusion-deformation method are discussed. The results are compared with those obtained from the single diffusivity equation. Implications for practical applications such as well testing are addressed. Results indicate that the diffusion-deformation behaviour of porous material affects the transient pressure response near a horizontal well. Evaluation by conventional well testing, based as it is on the single diffusion equation, would likely result in an overestimate of the permeability value. Comparison of results between the coupled diffusion-deformation approach and the single diffusion equation suggests that a better prediction of pressure response could be derived from total compressibility than by using only fluid compressibility. 6 refs., 9 figs.

  6. Both very low- and very high in vitro cytokine responses were associated with infant death in low-birth-weight children from Guinea Bissau.

    Directory of Open Access Journals (Sweden)

    Andreas Andersen

    Full Text Available The mechanisms behind heterologous immunity and non-specific effects of vaccines on mortality are not well understood. We examined associations between cytokine responses and subsequent mortality in low-birth-weight infants in Guinea-Bissau.A low-birth-weight trial randomized children to Bacille Calmette-Guérin (BCG at birth or later according to local policy. Blood samples were obtained from a sub-group at age 6 weeks. Interleukin (IL-5, IL-10, IL-13, interferon (IFN-γ, and tumor necrosis factor (TNF-α were measured in whole-blood cell cultures stimulated with lipopolysaccharide (LPS, phytohaemagglutinin (PHA, or purified protein derivative (PPD. The outcome was mortality between bleeding and 1 year of age. Non-linear associations between cytokine responses and mortality were examined.Cytokine measurements were available from 390 children. The mortality rate (MR was high (6.8/100 person-years-observation (PYO. Both low and high cytokine responses to LPS and PHA were associated with high mortality (MR up to 25/100 PYO in the lowest 10% and 9.2/100 PYO in the highest 10%. In BCG-vaccinated children, higher IFN-γ responses to PPD were associated with better survival (MR ratio = 0.43 (0.24-0.77.Data presented a rare opportunity to explore associations between cytokine responses and mortality. Both low and high cytokine responses were associated with high mortality; a balanced response to invading pathogens seems preferable.

  7. Both very low- and very high in vitro cytokine responses were associated with infant death in low-birth-weight children from Guinea Bissau.

    Science.gov (United States)

    Andersen, Andreas; Jensen, Kristoffer J; Erikstrup, Christian; Ravn, Henrik; Fisker, Ane B; Lisse, Ida M; Sartono, Erliyani; Aaby, Peter; Yazdanbakhsh, Maria; Benn, Christine S

    2014-01-01

    The mechanisms behind heterologous immunity and non-specific effects of vaccines on mortality are not well understood. We examined associations between cytokine responses and subsequent mortality in low-birth-weight infants in Guinea-Bissau. A low-birth-weight trial randomized children to Bacille Calmette-Guérin (BCG) at birth or later according to local policy. Blood samples were obtained from a sub-group at age 6 weeks. Interleukin (IL)-5, IL-10, IL-13, interferon (IFN)-γ, and tumor necrosis factor (TNF)-α were measured in whole-blood cell cultures stimulated with lipopolysaccharide (LPS), phytohaemagglutinin (PHA), or purified protein derivative (PPD). The outcome was mortality between bleeding and 1 year of age. Non-linear associations between cytokine responses and mortality were examined. Cytokine measurements were available from 390 children. The mortality rate (MR) was high (6.8/100 person-years-observation (PYO)). Both low and high cytokine responses to LPS and PHA were associated with high mortality (MR up to 25/100 PYO in the lowest 10% and 9.2/100 PYO in the highest 10%). In BCG-vaccinated children, higher IFN-γ responses to PPD were associated with better survival (MR ratio = 0.43 (0.24-0.77)). Data presented a rare opportunity to explore associations between cytokine responses and mortality. Both low and high cytokine responses were associated with high mortality; a balanced response to invading pathogens seems preferable.

  8. Inhibition of P2X7 receptor ameliorates transient global cerebral ischemia/reperfusion injury via modulating inflammatory responses in the rat hippocampus

    Directory of Open Access Journals (Sweden)

    Chu Ketan

    2012-04-01

    Full Text Available Abstract Background Neuroinflammation plays an important role in cerebral ischemia/reperfusion (I/R injury. The P2X7 receptor (P2X7R has been reported to be involved in the inflammatory response of many central nervous system diseases. However, the role of P2X7Rs in transient global cerebral I/R injury remains unclear. The purpose of this study is to determine the effects of inhibiting the P2X7R in a rat model of transient global cerebral I/R injury, and then to explore the association between the P2X7R and neuroinflammation after transient global cerebral I/R injury. Methods Immediately after infusion with the P2X7R antagonists Brilliant blue G (BBG, adenosine 5′-triphosphate-2′,3′-dialdehyde (OxATP or A-438079, 20 minutes of transient global cerebral I/R was induced using the four-vessel occlusion (4-VO method in rats. Survival rate was calculated, neuronal death in the hippocampal CA1 region was observed using H & E staining, and DNA cleavage was observed by deoxynucleotidyl transferase-mediated UTP nick end labeling TUNEL. In addition, behavioral deficits were measured using the Morris water maze, and RT-PCR and immunohistochemical staining were performed to measure the expression of IL-1β, TNF-α and IL-6, and to identify activated microglia and astrocytes. Results The P2X7R antagonists protected against transient global cerebral I/R injury in a dosage-dependent manner. A high dosage of BBG (10 μg and A-0438079 (3 μg, and a low dosage of OxATP (1 μg significantly increased survival rates, reduced I/R-induced learning memory deficit, and reduced I/R-induced neuronal death, DNA cleavage, and glial activation and inflammatory cytokine overexpression in the hippocampus. Conclusions Our study indicates that inhibiting P2X7Rs protects against transient global cerebral I/R injury by reducing the I/R-induced inflammatory response, which suggests inhibition of P2X7Rs may be a promising therapeutic strategy for clinical treatment of

  9. Dose-dependent suppression by ethanol of transient auditory 40-Hz response.

    Science.gov (United States)

    Jääskeläinen, I P; Hirvonen, J; Saher, M; Pekkonen, E; Sillanaukee, P; Näätänen, R; Tiitinen, H

    2000-02-01

    Acute alcohol (ethanol) challenge is known to induce various cognitive disturbances, yet the neural basis of the effect is poorly known. The auditory transient evoked gamma-band (40-Hz) oscillatory responses have been suggested to be associated with various perceptual and cognitive functions in humans; however, alcohol effects on auditory 40-Hz responses have not been investigated to date. The objective of the study was to test the dose-related impact of alcohol on auditory transient evoked 40-Hz responses during a selective-attention task. Ten healthy social drinkers ingested, in four separate sessions, 0.00, 0. 25, 0.50, or 0.75 g/kg of 10% (v/v) alcohol solution. The order of the sessions was randomized and a double-blind procedure was employed. During a selective attention task, 300-Hz standard and 330-Hz deviant tones were presented to the left ear, and 1000-Hz standards and 1100-Hz deviants to the right ear of the subjects (P=0. 425 for each standard, P=0.075 for each deviant). The subjects attended to a designated ear, and were to detect the deviants therein while ignoring tones to the other ear. The auditory transient evoked 40-Hz responses elicited by both the attended and unattended standard tones were significantly suppressed by the 0.50 and 0.75 g/kg alcohol doses. Alcohol suppresses auditory transient evoked 40-Hz oscillations already with moderate blood alcohol concentrations. Given the putative role of gamma-band oscillations in cognition, this finding could be associated with certain alcohol-induced cognitive deficits.

  10. Analysis of transient thermal response in the outlet plenum of an LMFBR

    International Nuclear Information System (INIS)

    Yang, J.W.

    1976-05-01

    A two-zone mixing model based on the lumped-parameter approach was developed for the analysis of transient thermal response in the upper outlet plenum of an LMFBR. The one-dimensional turbulent jet flow equations were solved to determine the maximum penetration of the core flow. The maximum penetration is used as the criterion for dividing the sodium region into two mixing zones. The lumped-parameter model considers the transient sodium temperature affected by the thermal expansion of sodium, heat transfer with cover gas, heat capacity of different sections of metal and the addition of bypass flow into the plenum. Numerical calculations were performed for two cases. The first case corresponds to a normal scram followed by flow coast-down. The second case represents the double-ended pipe rupture at the inlet of cold leg followed by reactor scram. The results indicate that effects of flow stratification, chimney height, metal heat capacity and bypass flow are important for transient sodium temperature calculation. Thermal expansion of sodium and heat transfer with the cover gas does not play any significant role on sodium temperature. This two-zone mixing model will be a part of the thermohydraulic transient code SSC

  11. Adjuvant effect of Asparagus racemosus Willd. derived saponins in antibody production, allergic response and pro-inflammatory cytokine modulation.

    Science.gov (United States)

    Tiwari, Nimisha; Gupta, Vivek Kumar; Pandey, Pallavi; Patel, Dinesh Kumar; Banerjee, Suchitra; Darokar, Mahendra Pandurang; Pal, Anirban

    2017-02-01

    The study manifests the immunoadjuvant potential of saponin rich fraction from Asparagus racemosus in terms of cellular and humoral immune response that can be exploited against microbial infections. Asparagus racemosus (AR) has been attributed as an adaptogen and rasayana in traditional medication systems for enhancing the host defence mechanism. Spectrophotometric and HPTLC analysis ensured the presence of saponins. The saponin rich fractions were tested for immunoadjuvant property in ovalbumin immunised mice for the humoral response, quantified in terms of prolonged antibody production upto a duration of 56days. Proinflammatory cytokines (IL-6 and TNF) were estimated for the cellular immune response in LPS stimulated primary murine macrophages. The safety evaluation in terms of cytotoxicity and allergic response has also been evaluated through in-vitro (MTT) and in-vivo (IgE) respectively. ARS significantly inhibited the pro-inflammatory cytokines, in LPS stimulated murine macrophages with no intrinsic cytotoxicity. The significant increase in IgG production infers the utility of ARS for prolonged humoral response. Further, the antigen specific response of IL-12 at early stage and IgE titres also suggests the generation of cellular immune response and low allergic reaction respectively, as compared to conventional adjuvants. IL-6 and TNF fluctuations in LPS stimulated and non-stimulated macrophages along with IgG and IL-12 also confirmed the Th1/Th2 modulating effect of ARS. The study indicates potential effect of ARS as an adjuvant for the stimulation of cellular immune response in addition to generating a sustained adaptive response without any adverse effects paving way for further validation with pathogenic organisms. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  12. A free radical scavenger edaravone suppresses systemic inflammatory responses in a rat transient focal ischemia model.

    Science.gov (United States)

    Fujiwara, Norio; Som, Angel T; Pham, Loc-Duyen D; Lee, Brian J; Mandeville, Emiri T; Lo, Eng H; Arai, Ken

    2016-10-28

    A free radical scavenger edaravone is clinically used in Japan for acute stroke, and several basic researches have carefully examined the mechanisms of edaravone's protective effects. However, its actions on pro-inflammatory responses under stroke are still understudied. In this study, we subjected adult male Sprague-Dawley rats to 90-min middle cerebral artery (MCA) occlusion followed by reperfusion. Edaravone was treated twice via tail vein; after MCA occlusion and after reperfusion. As expected, edaravone-treated group showed less infarct volume and edema formation compared with control group at 24-h after an ischemic onset. Furthermore, edaravone reduced the levels of plasma interleukin (IL)-1β and matrix metalloproteinase-9 at 3-h after ischemic onset. Several molecules besides IL-1β and MMP-9 are involved in inflammatory responses under stroke conditions. Therefore, we also examined whether edaravone treatment could decrease a wide range of pro-inflammatory cytokines/chemokines by testing rat plasma samples with a rat cytokine array. MCAO rats showed elevations in plasma levels of CINC-1, Fractalkine, IL-1α, IL-1ra, IL-6, IL-10, IP-10, MIG, MIP-1α, and MIP-3α, and all these increases were reduced by edaravone treatment. These data suggest that free radical scavengers may reduce systemic inflammatory responses under acute stroke conditions, and therefore, oxidative stress can be still a viable target for acute stroke therapy. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  13. Cytokine Response, Tract-Specific Fractional Anisotropy, and Brain Morphometry in Post-Stroke Cognitive Impairment.

    Science.gov (United States)

    Kulesh, Aleksey; Drobakha, Viktor; Kuklina, Elena; Nekrasova, Irina; Shestakov, Vladimir

    2018-07-01

    Post-stroke cognitive impairment is a clinically heterogeneous condition and its types have a different course and prognosis. The aim of the present study is to address the roles of inflammation, white matter pathology, and brain atrophy in different neuropsychological types of cognitive impairment in the acute period of ischemic stroke. In 92 patients, we performed an assessment of the cognitive status and measured concentrations of cytokines (interleukin [IL]-1β, IL-6, tumor necrosis factor-alpha, IL-10) in liquor and serum, as well as a number of magnetic resonance imaging (MRI) morphometric parameters and fractional anisotropy. The control group consisted of 14 individuals without cerebrovascular disease. All patients had a higher level of IL-10 in serum than the control group. Patients with dysexecutive cognitive impairment had a higher concentration of IL-1β and IL-10 in liquor, IL-6 level in serum, and a lower fractional anisotropy of the ipsilateral thalamus than patients with normal cognition. Patients with mixed cognitive impairment were characterized by a lower fractional anisotropy of contralateral fronto-occipital fasciculus, compared with patients with dysexecutive cognitive impairment. Patients with both dysexecutive and mixed cognitive deficit had a wide area of leukoaraiosis and a reduced fractional anisotropy of the contralateral cingulum, compared with patients without cognitive impairment. Also, we found numerous correlations between cognitive status and levels of cytokines, MRI morphometric parameters, and fractional anisotropy of certain regions of the brain. The concentrations of cytokines in serum and cerebrospinal fluid studied in combination with MRI morphometric parameters and fractional anisotropy appear to be informative biomarkers of clinical types of post-stroke cognitive impairment. Copyright © 2018 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  14. Impaired production of proinflammatory cytokines in response to lipopolysaccharide (LPS) stimulation in elderly humans

    DEFF Research Database (Denmark)

    Bruunsgaard, H.; Pedersen, Agnes Nadelmann; Schroll, M.

    1999-01-01

    following LPS stimulation, representing an ex vivo model of sepsis. Levels of tumour necrosis factor-alpha (TNF-alpha), IL-1 beta and IL-6 in whole blood supernatants were measured after in vitro LPS stimulation for 24 h in 168 elderly humans aged 81 years from the 1914 cohort in Glostrup, Denmark and in 91...... of proinflammatory cytokines compared with young men, but this difference was blurred by ageing. No relation was found between circulating plasma levels of TNF-alpha and levels after in vitro LPS stimulation. In conclusion, decreased production of TNF-alpha and IL-1 beta after exposure to LPS may reflect impaired...

  15. Attenuation of massive cytokine response to the staphylococcal enterotoxin B superantigen by the innate immunomodulatory protein lactoferrin

    Science.gov (United States)

    Hayworth, J L; Kasper, K J; Leon-Ponte, M; Herfst, C A; Yue, D; Brintnell, W C; Mazzuca, D M; Heinrichs, D E; Cairns, E; Madrenas, J; Hoskin, D W; McCormick, J K; Haeryfar, S M M

    2009-01-01

    Staphylococcal enterotoxin B (SEB) is a pyrogenic exotoxin and a potent superantigen which causes massive T cell activation and cytokine secretion, leading to profound immunosuppression and morbidity. The inhibition of SEB-induced responses is thus considered a goal in the management of certain types of staphylococcal infections. Lactoferrin (LF) is a multi-functional glycoprotein with both bacteriostatic and bactericidal activities. In addition, LF is known to have potent immunomodulatory properties. Given the anti-microbial and anti-inflammatory properties of this protein, we hypothesized that LF can modulate T cell responses to SEB. Here, we report that bovine LF (bLF) was indeed able to attenuate SEB-induced proliferation, interleukin-2 production and CD25 expression by human leucocyte antigen (HLA)-DR4 transgenic mouse T cells. This inhibition was not due to bLF's iron-binding capacity, and could be mimicked by the bLF-derived peptide lactoferricin. Cytokine secretion by an engineered SEB-responsive human Jurkat T cell line and by peripheral blood mononuclear cells from healthy donors was also inhibited by bLF. These findings reveal a previously unrecognized property of LF in modulation of SEB-triggered immune activation and suggest a therapeutic potential for this naturally occurring protein during toxic shock syndrome. PMID:19659771

  16. Single cell analysis of innate cytokine responses to pattern recognition receptor stimulation in children across four continents

    Science.gov (United States)

    Smolen, Kinga K; Cai, Bing; Fortuno, Edgardo S; Gelinas, Laura; Larsen, Martin; Speert, David P; Chamekh, Mustapha; Kollmann, Tobias R

    2014-01-01

    Innate immunity instructs adaptive immunity, and suppression of innate immunity is associated with increased risk for infection. We had previously shown that whole blood cellular components from a cohort of South African children secreted significantly lower levels of most cytokines following stimulation of pattern recognition receptors (PRR) as compared to whole blood from cohorts of Ecuadorian, Belgian, or Canadian children. To begin dissecting the responsible molecular mechanisms, we now set out to identify the relevant cellular source of these differences. Across the four cohorts represented in our study, we identified significant variation in the cellular composition of whole blood; however, significant reduction of the intracellular cytokine production on the single cell level was only detected in South African childrens’ monocytes, cDC, and pDC. We also uncovered a marked reduction in polyfunctionality for each of these cellular compartments in South African children as compared to children from other continents. Together our data identify differences in cell composition as well as profoundly lower functional responses of innate cells in our cohort of South African children. A possible link between altered innate immunity and increased risk for infection or lower response to vaccines in South African infants needs to be explored. PMID:25135829

  17. Enhanced Medial Collateral Ligament Healing using Mesenchymal Stem Cells: Dosage Effects on Cellular Response and Cytokine Profile

    Science.gov (United States)

    Saether, Erin E.; Chamberlain, Connie S.; Leiferman, Ellen M.; Kondratko-Mittnacht, Jaclyn R.; Li, Wan Ju; Brickson, Stacey L.; Vanderby, Ray

    2013-01-01

    Mesenchymal stem cells (MSCs) have potential therapeutic applications for musculoskeletal injuries due to their ability to differentiate into several tissue cell types and modulate immune and inflammatory responses. These immune-modulatory properties were examined in vivo during early stage rat medial collateral ligament healing. Two different cell doses (low dose 1×106 or high dose 4×106 MSCs) were administered at the time of injury and compared with normal ligament healing at days 5 and 14 post-injury. At both times, the high dose MSC group demonstrated a significant decrease in M2 macrophages compared to controls. At day 14, fewer M1 macrophages were detected in the low dose group compared to the high dose group. These results, along with significant changes in procollagen I, proliferating cells, and endothelialization suggest that MSCs can alter the cellular response during healing in a dose-dependent manner. The higher dose ligaments also had increased expression of several pro-inflammatory cytokines at day 5 (IL-1β, IFNγ, IL-2) and increased expression of IL-12 at day 14. Mechanical testing at day 14 revealed increased failure strength and stiffness in low dose ligaments compared to controls. Based on these improved mechanical properties, MSCs enhanced functional healing when applied at a lower dose. Different doses of MSCs uniquely affected the cellular response and cytokine expression in healing ligaments. Interestingly, the lower dose of cells proved to be most effective in improving functional properties. PMID:24174129

  18. Cytokine responses to Staphylococcus aureus bloodstream infection differ between patient cohorts that have different clinical courses of infection.

    Science.gov (United States)

    McNicholas, Sinead; Talento, Alida Fe; O'Gorman, Joanne; Hannan, Margaret M; Lynch, Maureen; Greene, Catherine M; Humphreys, Hilary; Fitzgerald-Hughes, Deirdre

    2014-11-15

    The clinical course of Staphylococcus aureus bloodstream infection is unpredictable and bacterial virulence, host immune response and patient characteristics are among the factors that contribute to the clinical course of infection. To investigate the relationship between cytokine response and clinical outcome, circulating cytokine levels were investigated in response to S. aureus bloodstream infection in patients with different clinical courses of infection. A prospective study was carried out in 61 patients with S. aureus bloodstream infection and circulating levels of IL-6, GRO-γ, RANTES and leptin were assessed over the course of the infection. Levels were compared in patients with complicated courses of infection (e.g. infective endocarditis) versus uncomplicated courses of S. aureus bloodstream infection and methicillin-resistant S. aureus Vs methicillin-susceptible S. aureus infection. Significantly lower leptin levels (p < 0.05) and significantly higher IL-6 levels (p < 0.05) were detected at laboratory diagnosis in patients with complicated compared to uncomplicated S. aureus bloodstream infection. Significantly higher levels of GRO-γ were associated with MRSA infection compared to MSSA infection. IL-6 may be an early inflammatory marker of complicated S. aureus bloodstream infection. Leptin may be protective against the development of a complicated S. aureus bloodstream infection.

  19. Pubertal-related changes in hypothalamic-pituitary-adrenal axis reactivity and cytokine secretion in response to an immunological stressor.

    Science.gov (United States)

    Goble, K H; Bain, Z A; Padow, V A; Lui, P; Klein, Z A; Romeo, R D

    2011-02-01

    Pubertal development is marked by profound changes in stress reactivity. For example, following a brief stressor, such as foot shock, ether inhalation or restraint, prepubertal rats display a prolonged adrenocorticotrophic hormone (ACTH) and corticosterone response that takes twice as long to return to baseline compared to adults. Pubertal-related differences in the recovery of the hormonal stress response following a more protracted systemic stressor, such as an immunological challenge, have not yet been investigated. Moreover, it is unclear whether an immunological stressor leads to a differential cytokine response in animals before and after pubertal maturation. To examine these issues, we used a single injection of lipopolysaccharide (LPS; 0.1 mg/kg) to induce a hormonal stress and innate immune response and measured plasma ACTH, corticosterone, and the pro-inflammatory cytokines interleukin (IL)-1β and IL-6 in prepubertal and adult male rats 0, 2, 4, 6, 8, or 24 h after LPS exposure. In a follow-up experiment, we assessed neural activation, as indexed by FOS immunohistochemistry, in the paraventricular nucleus of the hypothalamus (PVN) in prepubertal and adult males 0, 4, 8, or 24 h after a 0.1 mg/kg injection of LPS. By contrast to the prolonged response observed in prepubertal animals following a variety of acute stressors, we found that corticosterone and IL-6 responses induced by LPS recover toward baseline faster in prepubertal compared to adult rats. Along with these different peripheral responses, we also found that LPS-induced neural activation in the PVN of prepubertal animals showed a faster return to baseline compared to adults. Together, these data indicate that prepubertal and adult animals react in distinct ways, both peripherally and centrally, to an immunological stressor. © 2011 The Authors. Journal of Neuroendocrinology © 2011 Blackwell Publishing Ltd.

  20. Transient response of nonideal ion-selective microchannel-nanochannel devices

    Science.gov (United States)

    Leibowitz, Neta; Schiffbauer, Jarrod; Park, Sinwook; Yossifon, Gilad

    2018-04-01

    We report evidence of variation in ion selectivity of a fabricated microchannel-nanochannel device resulting in the appearance of a distinct local maximum in the overlimiting chronopotentiometric response. In this system consisting of shallow microchannels joined by a nanochannel, viscous shear at the microchannel walls suppresses the electro-osmotic instability and prevents any associated contribution to the nonmonotonic response. Thus, this response is primarily electrodiffusive. Numerical simulations indicate that concentration polarization develops not only within the microchannel but also within the nanochannel itself, with a local voltage maximum in the chronopotentiometric response correlated with interfacial depletion and having the classic i-2 Sands time dependence. Furthermore, the occurrence of the local maxima is correlated with the change in selectivity due to internal concentration polarization. Understanding the transient nonideal permselective response is essential for obtaining fundamental insight and for optimizing efficient operation of practical fabricated nanofluidic and membrane devices.

  1. Curcumin regulates airway epithelial cell cytokine responses to the pollutant cadmium

    International Nuclear Information System (INIS)

    Rennolds, Jessica; Malireddy, Smitha; Hassan, Fatemat; Tridandapani, Susheela; Parinandi, Narasimham; Boyaka, Prosper N.; Cormet-Boyaka, Estelle

    2012-01-01

    Highlights: ► Cadmium induces secretion of IL-6 and IL-8 by two distinct pathways. ► Cadmium increases NAPDH oxidase activity leading to Erk activation and IL-8 secretion. ► Curcumin prevents cadmium-induced secretion of both IL-6 and IL-8 by airway cells. ► Curcumin could be use to suppress lung inflammation due to cadmium inhalation. -- Abstract: Cadmium is a toxic metal present in the environment and its inhalation can lead to pulmonary disease such as lung cancer and chronic obstructive pulmonary disease. These lung diseases are characterized by chronic inflammation. Here we show that exposure of human airway epithelial cells to cadmium promotes a polarized apical secretion of IL-6 and IL-8, two pivotal pro-inflammatory cytokines known to play an important role in pulmonary inflammation. We also determined that two distinct pathways controlled secretion of these proinflammatory cytokines by human airway epithelial cells as cadmium-induced IL-6 secretion occurs via an NF-κB dependent pathway, whereas IL-8 secretion involves the Erk1/2 signaling pathway. Interestingly, the natural antioxidant curcumin could prevent both cadmium-induced IL-6 and IL-8 secretion by human airway epithelial cells. In conclusion, curcumin could be used to prevent airway inflammation due to cadmium inhalation.

  2. Monoethylhexyl Phthalate Elicits an Inflammatory Response in Adipocytes Characterized by Alterations in Lipid and Cytokine Pathways.

    Science.gov (United States)

    Manteiga, Sara; Lee, Kyongbum

    2017-04-01

    A growing body of evidence links endocrine-disrupting chemicals (EDCs) with obesity-related metabolic diseases. While it has been shown that EDCs can predispose individuals toward adiposity by affecting developmental processes, little is known about the chemicals' effects on adult adipose tissue. Our aim was to study the effects of low, physiologically relevant doses of EDCs on differentiated murine adipocytes. We combined metabolomics, proteomics, and gene expression analysis to characterize the effects of mono-ethylhexyl phthalate (MEHP) in differentiated adipocytes. Repeated exposure to MEHP over several days led to changes in metabolite and enzyme levels indicating elevated lipogenesis and lipid oxidation. The chemical exposure also increased expression of major inflammatory cytokines, including chemotactic factors. Proteomic and gene expression analysis revealed significant alterations in pathways regulated by peroxisome proliferator activated receptor-γ (PPARγ). Inhibiting the nuclear receptor's activity using a chemical antagonist abrogated not only the alterations in PPARγ-regulated metabolic pathways, but also the increases in cytokine expression. Our results show that MEHP can induce a pro-inflammatory state in differentiated adipocytes. This effect is at least partially mediated PPARγ.

  3. Curcumin regulates airway epithelial cell cytokine responses to the pollutant cadmium

    Energy Technology Data Exchange (ETDEWEB)

    Rennolds, Jessica; Malireddy, Smitha; Hassan, Fatemat; Tridandapani, Susheela; Parinandi, Narasimham [Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, The Ohio State University, Columbus, OH 43210 (United States); Boyaka, Prosper N. [Department of Veterinary Biosciences, The Ohio State University, Columbus, OH 43210 (United States); Cormet-Boyaka, Estelle, E-mail: Estelle.boyaka@osumc.edu [Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, The Ohio State University, Columbus, OH 43210 (United States)

    2012-01-06

    Highlights: Black-Right-Pointing-Pointer Cadmium induces secretion of IL-6 and IL-8 by two distinct pathways. Black-Right-Pointing-Pointer Cadmium increases NAPDH oxidase activity leading to Erk activation and IL-8 secretion. Black-Right-Pointing-Pointer Curcumin prevents cadmium-induced secretion of both IL-6 and IL-8 by airway cells. Black-Right-Pointing-Pointer Curcumin could be use to suppress lung inflammation due to cadmium inhalation. -- Abstract: Cadmium is a toxic metal present in the environment and its inhalation can lead to pulmonary disease such as lung cancer and chronic obstructive pulmonary disease. These lung diseases are characterized by chronic inflammation. Here we show that exposure of human airway epithelial cells to cadmium promotes a polarized apical secretion of IL-6 and IL-8, two pivotal pro-inflammatory cytokines known to play an important role in pulmonary inflammation. We also determined that two distinct pathways controlled secretion of these proinflammatory cytokines by human airway epithelial cells as cadmium-induced IL-6 secretion occurs via an NF-{kappa}B dependent pathway, whereas IL-8 secretion involves the Erk1/2 signaling pathway. Interestingly, the natural antioxidant curcumin could prevent both cadmium-induced IL-6 and IL-8 secretion by human airway epithelial cells. In conclusion, curcumin could be used to prevent airway inflammation due to cadmium inhalation.

  4. Application of ADINA fluid element for transient response analysis of fluid-structure system

    International Nuclear Information System (INIS)

    Sakurai, Y.; Kodama, T.; Shiraishi, T.

    1985-01-01

    Pressure propagation and Fluid-Structure Interaction (FSI) in 3D space were simulated by general purpose finite element program ADINA using the displacement-based fluid element which presumes inviscid and compressible fluid with no net flow. Numerical transient solution was compared with the measured data of an FSI experiment and was found to fairly agree with the measured. In the next step, post analysis was conducted for a blowdown experiment performed with a 1/7 scaled reactor pressure vessel and a flexible core barrel and the code performance was found to be satisfactory. It is concluded that the transient response of the core internal structure of a PWR during the initial stage of LOCA can be analyzed by the displacement-based finite fluid element and the structural element. (orig.)

  5. Effect of helium pressure on the response of unirradiated UO2 subjected to thermal transients

    International Nuclear Information System (INIS)

    Fenske, G.R.; Chapello, P.M.; Emerson, J.E.; Poeppel, R.B.

    1983-01-01

    The effect of helium pressure on the transient response of unirradiated depleted UO 2 subjected to simulated hypothetical loss-of-flow accidents in a gas-cooled fast reactor was examined by use of the direct electrical heating technique. Transient tests were performed at pressures ranging from 7 to 10 X 10 5 Pa(7 to 10 atm) to 7 to 8 MPa (70 to 80 atm) on radially restrained and unrestrained fuel segments. The average heating rates ranged from about17 to 240 J/g x s. The results indicate that while the mechanical integrity of the fuel segment was independent of the test pressure, the rapid ejection of molten fuel from pellet interfaces of unrestrained fuel, observed at the lower pressures, was delayed or suppressed at the higher pressures

  6. Geometrically Nonlinear Transient Response of Laminated Plates with Nonlinear Elastic Restraints

    Directory of Open Access Journals (Sweden)

    Shaochong Yang

    2017-01-01

    Full Text Available To investigate the dynamic behavior of laminated plates with nonlinear elastic restraints, a varied constraint force model and a systematic numerical procedure are presented in this work. Several kinds of typical relationships of force-displacement for spring are established to simulate the nonlinear elastic restraints. In addition, considering the restraining moments of flexible pads, the pads are modeled by translational and rotational springs. The displacement- dependent constraint forces are added to the right-hand side of equations of motion and treated as additional applied loads. These loads can be explicitly defined, via an independent set of nonlinear load functions. The time histories of transverse displacements at typical points of the laminated plate are obtained through the transient analysis. Numerical examples show that the present method can effectively treat the geometrically nonlinear transient response of plates with nonlinear elastic restraints.

  7. The transient response for different types of erodable surface thermocouples using finite element analysis

    Directory of Open Access Journals (Sweden)

    Mohammed Hussein

    2007-01-01

    Full Text Available The transient response of erodable surface thermocouples has been numerically assessed by using a two dimensional finite element analysis. Four types of base metal erodable surface thermocouples have been examined in this study, included type-K (alumel-chromel, type-E (chromel-constantan, type-T (copper-constantan, and type-J (iron-constantan with 50 mm thick- ness for each. The practical importance of these types of thermocouples is to be used in internal combustion engine studies and aerodynamics experiments. The step heat flux was applied at the surface of the thermocouple model. The heat flux from the measurements of the surface temperature can be commonly identified by assuming that the heat transfer within these devices is one-dimensional. The surface temperature histories at different positions along the thermocouple are presented. The normalized surface temperature histories at the center of the thermocouple for different types at different response time are also depicted. The thermocouple response to different heat flux variations were considered by using a square heat flux with 2 ms width, a sinusoidal surface heat flux variation width 10 ms period and repeated heat flux variation with 2 ms width. The present results demonstrate that the two dimensional transient heat conduction effects have a significant influence on the surface temperature history measurements made with these devices. It was observed that the surface temperature history and the transient response for thermocouple type-E are higher than that for other types due to the thermal properties of this thermocouple. It was concluded that the thermal properties of the surrounding material do have an impact, but the properties of the thermocouple and the insulation materials also make an important contribution to the net response.

  8. Xanomeline suppresses excessive pro-inflammatory cytokine responses through neural signal-mediated pathways and improves survival in lethal inflammation

    Science.gov (United States)

    Rosas-Ballina, Mauricio; Ferrer, Sergio Valdés; Dancho, Meghan; Ochani, Mahendar; Katz, David; Cheng, Kai Fan; Olofsson, Peder S.; Chavan, Sangeeta S.; Al-Abed, Yousef; Tracey, Kevin J.; Pavlov, Valentin A.

    2014-01-01

    Inflammatory conditions characterized by excessive immune cell activation and cytokine release, are associated with bidirectional immune system-brain communication, underlying sickness behavior and other physiological responses. The vagus nerve has an important role in this communication by conveying sensory information to the brain, and brain-derived immunoregulatory signals that suppress peripheral cytokine levels and inflammation. Brain muscarinic acetylcholine receptor (mAChR)-mediated cholinergic signaling has been implicated in this regulation. However, the possibility of controlling inflammation by peripheral administration of centrally-acting mAChR agonists is unexplored. To provide insight we used the centrally-acting M1 mAChR agonist xanomeline, previously developed in the context of Alzheimer’s disease and schizophrenia. Intraperitoneal administration of xanomeline significantly suppressed serum and splenic TNF levels, alleviated sickness behavior, and increased survival during lethal murine endotoxemia. The anti-inflammatory effects of xanomeline were brain mAChR-mediated and required intact vagus nerve and splenic nerve signaling. The anti-inflammatory efficacy of xanomeline was retained for at least 20h, associated with alterations in splenic lymphocyte, and dendritic cell proportions, and decreased splenocyte responsiveness to endotoxin. These results highlight an important role of the M1 mAChR in a neural circuitry to spleen in which brain cholinergic activation lowers peripheral pro-inflammatory cytokines to levels favoring survival. The therapeutic efficacy of xanomeline was also manifested by significantly improved survival in preclinical settings of severe sepsis. These findings are of interest for strategizing novel therapeutic approaches in inflammatory diseases. PMID:25063706

  9. Oral administration of Saccharomyces boulardii alters duodenal morphology, enzymatic activity and cytokine production response in broiler chickens.

    Science.gov (United States)

    Sun, Yajing; Rajput, Imran Rashid; Arain, Muhammad Asif; Li, Yanfei; Baloch, Dost Muhammad

    2017-08-01

    The present study evaluated the effects of Saccharomyces boulardii on duodenal digestive enzymes, morphology and cytokine induction response in broiler chicken. A total of 200 birds were allotted into two groups (n = 100) and each group divided into five replications (n = 20). The control group was fed basal diet in addition to antibiotic (virginiamycin 20 mg/kg), and treatment group received (1 × 10 8  colony-forming units/kg feed) S. boulardii in addition to basal diet lasting for 72 days. The results compared to control group revealed that adenosine triphosphatase, gamma glutamyl transpeptidase, lipase and trypsin activities were higher, while, no significant improvement was observed in amylase activities in the duodenum of the treatment group. Moreover, morphological findings showed that villus height, width and number of goblet cells markedly increased. Additionally, transmission electron microscopy visualized that villus height, width and structural condensation significantly increased in the treatment group. The immunohistological observations showed increased numbers of immunoglobulin A (IgA)-positive cells in the duodenum of the treatment group. Meanwhile, cytokine production levels of tumor necrosis factor-α, interleukin (IL)-10, transforming growth factor-β and secretory IgA markedly increased, and IL-6 statistically remained unchanged as compared to the control group. These findings illustrated that initial contact of S. boulardii to the duodenum has significant impact in improving enzymatic activity, intestinal morphology and cytokine response in broiler chicken. © 2016 Japanese Society of Animal Science.

  10. HECTR [Hydrogen Event: Containment Transient Response] analyses of the Nevada Test Site (NTS) premixed combustion experiments

    International Nuclear Information System (INIS)

    Wong, C.C.

    1988-11-01

    The HECTR (Hydrogen Event: Containment Transient Response) computer code has been developed at Sandia National Laboratories to predict the transient pressure and temperature responses within reactor containments for hypothetical accidents involving the transport and combustion of hydrogen. Although HECTR was designed primarily to investigate these phenomena in LWRs, it may also be used to analyze hydrogen transport and combustion experiments as well. It is in this manner that HECTR is assessed and empirical correlations, such as the combustion completeness and flame speed correlations for the hydrogen combustion model, if necessary, are upgraded. In this report, we present HECTR analyses of the large-scale premixed hydrogen combustion experiments at the Nevada Test Site (NTS) and comparison with the test results. The existing correlations in HECTR version 1.0, under certain conditions, have difficulty in predicting accurately the combustion completeness and burn time for the NTS experiments. By combining the combustion data obtained from the NTS experiments with other experimental data (FITS, VGES, ACUREX, and Whiteshell), a set of new and better combustion correlations was generated. HECTR prediction of the containment responses, using a single-compartment model and EPRI-provided combustion completeness and burn time, compares reasonably well against the test results. However, HECTR prediction of the containment responses using a multicompartment model does not compare well with the test results. This discrepancy shows the deficiency of the homogeneous burning model used in HECTR. To overcome this deficiency, a flame propagation model is highly recommended. 16 refs., 84 figs., 5 tabs

  11. Hypothermia Modulates Cytokine Responses After Neonatal Rat Hypoxic-Ischemic Injury and Reduces Brain Damage

    Directory of Open Access Journals (Sweden)

    Xiangpeng Yuan

    2014-11-01

    Full Text Available While hypothermia (HT is the standard-of-care for neonates with hypoxic ischemic injury (HII, the mechanisms underlying its neuroprotective effect are poorly understood. We examined ischemic core/penumbra and cytokine/chemokine evolution in a 10-day-old rat pup model of HII. Pups were treated for 24 hr after HII with HT (32℃; n = 18 or normothermia (NT, 35℃; n = 15. Outcomes included magnetic resonance imaging (MRI, neurobehavioral testing, and brain cytokine/chemokine profiling (0, 24, 48, and 72 hr post-HII. Lesion volumes (24 hr were reduced in HT pups (total 74%, p < .05; penumbra 68%, p < .05; core 85%, p = .19. Lesion volumes rebounded at 72 hr (48 hr post-HT with no significant differences between NT and HT pups. HT reduced interleukin-1β (IL-1β at all time points (p < .05; monocyte chemoattractant protein-1 (MCP-1 trended toward being decreased in HT pups (p = .09. The stem cell signaling molecule, stromal cell-derived factor-1 (SDF-1 was not altered by HT. Our data demonstrate that HT reduces total and penumbral lesion volumes (at 24 and 48 hr, potentially by decreasing IL-1β without affecting SDF-1. Disassociation between the increasing trend in HII volumes from 48 to 72 hr post-HII when IL-1β levels remained low suggests that after rewarming, mechanisms unrelated to IL-1β expression are likely to contribute to this delayed increase in injury. Additional studies should be considered to determine what these mechanisms might be and also to explore whether extending the duration or degree of HT might ameliorate this delayed increase in injury.

  12. Longer period of oral administration of aspartame on cytokine response in Wistar albino rats.

    Science.gov (United States)

    Choudhary, Arbind Kumar; Sheela Devi, Rathinasamy

    2015-03-01

    Aspartame is a non-nutritive sweetener particularly used in 'diet' and 'low calorie' products and also in a variety of foods, drugs and hygiene products. Aspartame is metabolized by gut esterases and peptidases to three common chemicals: the amino acids, aspartic acid and phenylalanine, and small amounts of methanol. The aim of the present study was to assess potential changes in molecular mediators of aspartame as a chemical stressor in rats. The effects of long-term administration of aspartame (40 mg/kg body weight/day) were tested in Wistar Albino rats. The treatment effects were assessed in different conditions, including control groups. After 90 days of treatment, circulating concentrations of different parameters were assessed: corticosterone, lipid peroxidation, antioxidant activity, nitric oxide, reduced glutathione and cytokines (interleukin 2, interleukin 4, tumor necrosis factor-α and interferon-γ). The results show that there was a significant increase in plasma corticosterone, serum lipid peroxidation and nitric oxide level along with a decrease in enzymatic and non-enzymatic antioxidant as well as significant decrease in interleukin 2, tumor necrosis factor-α and interferon-γ. There was also a significant increase in interleukin 4 irrespective of whether the animals were immunized or not. The findings clearly point out that aspartame acts as a chemical stressor because of increased corticosterone level and increased lipid peroxidation and nitric oxide level induce generation of free radicals in serum which may be the reason for variation of cytokine level and finally results in alteration of immune function. Aspartame metabolite methanol or formaldehyde may be the causative factors behind the changes observed. Copyright © 2014 SEEN. Published by Elsevier España, S.L.U. All rights reserved.

  13. T-helper cell-mediated proliferation and cytokine responses against recombinant Merkel cell polyomavirus-like particles.

    Directory of Open Access Journals (Sweden)

    Arun Kumar

    Full Text Available The newly discovered Merkel Cell Polyomavirus (MCPyV resides in approximately 80% of Merkel cell carcinomas (MCC. Causal role of MCPyV for this rare and aggressive skin cancer is suggested by monoclonal integration and truncation of large T (LT viral antigen in MCC cells. The mutated MCPyV has recently been found in highly purified leukemic cells from patients with chronic lymphocytic leukemia (CLL, suggesting a pathogenic role also in CLL. About 50-80% of adults display MCPyV-specific antibodies. The humoral immunity does not protect against the development of MCC, as neutralizing MCPyV antibodies occur in higher levels among MCC patients than healthy controls. Impaired T-cell immunity has been linked with aggressive MCC behavior. Therefore, cellular immunity appears to be important in MCPyV infection surveillance. In order to elucidate the role of MCPyV-specific Th-cell immunity, peripheral blood mononuclear cells (PBMC of healthy adults were stimulated with MCPyV VP1 virus-like particles (VLPs, using human bocavirus (HBoV VLPs and Candida albicans antigen as positive controls. Proliferation, IFN-γ, IL-13 and IL-10 responses were examined in 15 MCPyV-seropositive and 15 seronegative volunteers. With the MCPyV antigen, significantly stronger Th-cell responses were found in MCPyV-seropositive than MCPyV-seronegative subjects, whereas with the control antigens, the responses were statistically similar. The most readily detectable cytokine was IFN-γ. The MCPyV antigen tended to induce stronger IFN-γ responses than HBoV VLP antigen. Taken together, MCPyV-specific Th-cells elicit vigorous IFN-γ responses. IFN-γ being a cytokine with major antiviral and tumor suppressing functions, Th-cells are suggested to be important mediators of MCPyV-specific immune surveillance.

  14. Static Tensile and Transient Dynamic Response of Cracked Aluminum Plate Repaired with Composite Patch - Numerical Study

    Science.gov (United States)

    Khalili, S. M. R.; Shariyat, M.; Mokhtari, M.

    2014-06-01

    In this study, the central cracked aluminum plates repaired with two sided composite patches are investigated numerically for their response to static tensile and transient dynamic loadings. Contour integral method is used to define and evaluate the stress intensity factors at the crack tips. The reinforcement for the composite patches is carbon fibers. The effect of adhesive thickness and patch thickness and configuration in tensile loading case and pre-tension, pre-compression and crack length effect on the evolution of the mode I stress intensity factor (SIF) (KI) of the repaired structure under transient dynamic loading case are examined. The results indicated that KI of the central cracked plate is reduced by 1/10 to 1/2 as a result of the bonded composite patch repair in tensile loading case. The crack length and the pre-loads are more effective in repaired structure in transient dynamic loading case in which, the 100 N pre-compression reduces the maximum KI for about 40 %, and the 100 N pre-tension reduces the maximum KI after loading period, by about 196 %.

  15. Shock Wave Speed and Transient Response of PE Pipe with Steel-Mesh Reinforcement

    Directory of Open Access Journals (Sweden)

    Wuyi Wan

    2016-01-01

    Full Text Available A steel mesh can improve the tensile strength and stability of a polyethylene (PE pipe in a water supply pipeline system. However, it can also cause more severe water hammer hazard due to increasing wave speed. In order to analyze the influence of the steel mesh on the shock wave speed and transient response processes, an improved wave speed formula is proposed by incorporating the equivalent elastic modulus. A field measurement validates the wave speed formula. Moreover, the transient wave propagation and extreme pressures are simulated and compared by the method of characteristics (MOC for reinforced PE pipes with various steel-mesh densities. Results show that a steel mesh can significantly increase the shock wave speed in a PE pipe and thus can cause severe peak pressure and hydraulic surges in a water supply pipeline system. The proposed wave speed formula can more reasonably evaluate the wave speed and improve the transient simulation of steel-mesh-reinforced PE pipes.

  16. Human mesenchymal stromal cells transiently increase cytokine production by activated T cells before suppressing T-cell proliferation: effect of interferon-γ and tumor necrosis factor-α stimulation.

    Science.gov (United States)

    Cuerquis, Jessica; Romieu-Mourez, Raphaëlle; François, Moïra; Routy, Jean-Pierre; Young, Yoon Kow; Zhao, Jing; Eliopoulos, Nicoletta

    2014-02-01

    Mesenchymal stromal cells (MSCs) suppress T-cell proliferation, especially after activation with inflammatory cytokines. We compared the dynamic action of unprimed and interferon (IFN)-γ plus tumor necrosis factor (TNF)-α-pretreated human bone marrow-derived MSCs on resting or activated T cells. MSCs were co-cultured with allogeneic peripheral blood mononuclear cells (PBMCs) at high MSC-to-PBMC ratios in the absence or presence of concomitant CD3/CD28-induced T-cell activation. The kinetic effects of MSCs on cytokine production and T-cell proliferation, cell cycle and apoptosis were assessed. Unprimed MSCs increased the early production of IFN-γ and interleukin (IL)-2 by CD3/CD28-activated PBMCs before suppressing T-cell proliferation. In non-activated PBMC co-cultures, low levels of IL-2 and IL-10 synthesis were observed with MSCs in addition to low levels of CD69 expression by T cells and no T-cell proliferation. MSCs also decreased apoptosis in resting and activated T cells and inhibited the transition of these cells into the sub-G0/G1 and the S phases. With inhibition of indoleamine 2,3 dioxygenase, MSCs increased CD3/CD28-induced T-cell proliferation. After priming with IFN-γ plus TNF-α, MSCs were less potent at increasing cytokine production by CD3/CD28-activated PBMCs and more effective at inhibiting T-cell proliferation but had preserved anti-apoptotic functions. Unprimed MSCs induce a transient increase in IFN-γ and IL-2 synthesis by activated T cells. Pre-treatment of MSCs with IFN-γ plus TNF-α may increase their effectiveness and safety in vivo. Copyright © 2014 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

  17. Transient Response of Thin Wire above a Layered Half-Space Using TDIE/FDTD Hybrid Method

    Directory of Open Access Journals (Sweden)

    Bing Wei

    2012-01-01

    Full Text Available The TDIE/FDTD hybrid method is applied to calculate the transient responses of thin wire above a lossy layered half-space. The time-domain reflection of the layered half space is computed by one-dimensional modified FDTD method. Then, transient response of thin wire induced by two excitation sources (the incident wave and reflected wave is calculated by TDIE method. Finally numerical results are given to illustrate the feasibility and high efficiency of the presented scheme.

  18. Interactive effects of maternal cigarette smoke, heat stress, hypoxia, and lipopolysaccharide on neonatal cardiorespiratory and cytokine responses

    Science.gov (United States)

    McDonald, Fiona B.; Chandrasekharan, Kumaran; Wilson, Richard J. A.

    2016-01-01

    Maternal cigarette smoke (CS) exposure exhibits a strong epidemiological association with Sudden Infant Death Syndrome, but other environmental stressors, including infection, hyperthermia, and hypoxia, have also been postulated as important risk factors. This study examines whether maternal CS exposure causes maladaptations within homeostatic control networks by influencing the response to lipopolysaccharide, heat stress, and/or hypoxia in neonatal rats. Pregnant dams were exposed to CS or parallel sham treatments daily for the length of gestation. Offspring were studied at postnatal days 6–8 at ambient temperatures (Ta) of 33°C or 38°C. Within each group, rats were allocated to control, saline, or LPS (200 µg/kg) treatments. Cardiorespiratory patterns were examined using head-out plethysmography and ECG surface electrodes during normoxia and hypoxia (10% O2). Serum cytokine concentrations were quantified from samples taken at the end of each experiment. Our results suggest maternal CS exposure does not alter minute ventilation (V̇e) or heart rate (HR) response to infection or high temperature, but independently increases apnea frequency. CS also primes the inflammatory system to elicit a stronger cytokine response to bacterial insult. High Ta independently depresses V̇e but augments the hypoxia-induced increase in V̇e. Moreover, higher Ta increases HR during normoxia and hypoxia, and in the presence of an immune challenge, increases HR during normoxia, and reduces the increase normally associated with hypoxia. Thus, while most environmental risk factors increase the burden on the cardiorespiratory system in early life, hyperthermia and infection blunt the normal HR response to hypoxia, and gestational CS independently destabilizes breathing by increasing apneas. PMID:27733384

  19. Differential responsiveness of obese (fa/fa) and lean (Fa/Fa) Zucker rats to cytokine-induced anorexia.

    Science.gov (United States)

    Plata-Salamán, C R; Vasselli, J R; Sonti, G

    1997-01-01

    Pathophysiological and pharmacological concentrations of tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta) in the cerebrospinal fluid (CSF) induce anorexia in normal rats. Obesity in humans and rodents is associated with increased TNF-alpha messenger RNA and protein levels in various cell types. This suggests that obese individuals may have differential regulation of cytokine production and dissimilar responsiveness to cytokines. In the present study, we investigated the effects of the intracerebroventricular (ICV) microinfusion of TNF-alpha (50, 100, and 500 ng/rat), IL-1 beta (1.0, 4.0, and 8.0 ng), and TNF-alpha (100 ng) plus IL-1 beta (1.0 ng) on obese (fa/fa) and lean (Fa/Fa) Zucker rats. The results show that: TNF-alpha and IL-1 beta, and the concomitant administration of TNF-alpha and IL-1 beta decreased the short-term (4 hours), nighttime (12 hours), and total daily food intakes in obese and lean rats; IL-1 beta was more potent relative to TNF-alpha; obese rats showed greater responsiveness to IL-1 beta: 8.0 ng IL-1 beta, for example, decreased the 12-hour food intake by 52% in obese and 22% in lean rats. On the other hand, obese and lean rats did not exhibit a significantly different responsiveness to the anorexia induced by 50, 100, or 500 ng TNF-alpha at the 4-hour period; and the concomitant ICV administration of TNF-alpha and IL-1 beta induced anorexia with additive (4-hour period) or synergistic (12-hour and 24-hour periods) effects in obese rats. The effect of TNF-alpha plus IL-1 beta in lean rats was greater than additive for the 12-hour and 24-hour periods. The difference in suppression of total daily food intake by TNF-alpha plus IL-1 beta in obese (-43%) versus lean (-23%) rats was significantly different (p < 0.01). The results show that obese (fa/fa) and lean (Fa/Fa) Zucker rats have differential responsiveness to the ICV microinfusion of two different classes of cytokines.

  20. Abnormal autonomic cardiac response to transient hypoxia in sickle cell anemia

    International Nuclear Information System (INIS)

    Sangkatumvong, S; Khoo, M C K; Coates, T D

    2008-01-01

    The objective of this study was to non-invasively assess cardiac autonomic control in subjects with sickle cell anemia (SCA) by tracking the changes in heart rate variability (HRV) that occur following brief exposure to a hypoxic stimulus. Five African–American SCA patients and seven healthy control subjects were recruited to participate in this study. Each subject was exposed to a controlled hypoxic stimulus consisting of five breaths of nitrogen. Time-varying spectral analysis of HRV was applied to estimate the cardiac autonomic response to the transient episode of hypoxia. The confounding effects of changes in respiration on the HRV spectral indices were reduced by using a computational model. A significant decrease in the parameters related to parasympathetic control was detected in the post-hypoxic responses of the SCA subjects relative to normal controls. The spectral index related to sympathetic activity, on the other hand, showed a tendency to increase the following hypoxic stimulation, but the change was not significant. This study suggests that there is some degree of cardiovascular autonomic dysfunction in SCA that is revealed by the response to transient hypoxia

  1. The immunological response and post-treatment survival of DC-vaccinated melanoma patients are associated with increased Th1/Th17 and reduced Th3 cytokine responses.

    Science.gov (United States)

    Durán-Aniotz, Claudia; Segal, Gabriela; Salazar, Lorena; Pereda, Cristián; Falcón, Cristián; Tempio, Fabián; Aguilera, Raquel; González, Rodrigo; Pérez, Claudio; Tittarelli, Andrés; Catalán, Diego; Nervi, Bruno; Larrondo, Milton; Salazar-Onfray, Flavio; López, Mercedes N

    2013-04-01

    Immunization with autologous dendritic cells (DCs) loaded with a heat shock-conditioned allogeneic melanoma cell lysate caused lysate-specific delayed type hypersensitivity (DTH) reactions in a number of patients. These responses correlated with a threefold prolonged long-term survival of DTH(+) with respect to DTH(-) unresponsive patients. Herein, we investigated whether the immunological reactions associated with prolonged survival were related to dissimilar cellular and cytokine responses in blood. Healthy donors and melanoma patient's lymphocytes obtained from blood before and after vaccinations and from DTH biopsies were analyzed for T cell population distribution and cytokine release. Peripheral blood lymphocytes from melanoma patients have an increased proportion of Th3 (CD4(+) TGF-β(+)) regulatory T lymphocytes compared with healthy donors. Notably, DTH(+) patients showed a threefold reduction of Th3 cells compared with DTH(-) patients after DCs vaccine treatment. Furthermore, DCs vaccination resulted in a threefold augment of the proportion of IFN-γ releasing Th1 cells and in a twofold increase of the IL-17-producing Th17 population in DTH(+) with respect to DTH(-) patients. Increased Th1 and Th17 cell populations in both blood and DTH-derived tissues suggest that these profiles may be related to a more effective anti-melanoma response. Our results indicate that increased proinflammatory cytokine profiles are related to detectable immunological responses in vivo (DTH) and to prolonged patient survival. Our study contributes to the understanding of immunological responses produced by DCs vaccines and to the identification of follow-up markers for patient outcome that may allow a closer individual monitoring of patients.

  2. A Decentralized Current-Sharing Controller Endows Fast Transient Response to Parallel DC-DC Converters

    DEFF Research Database (Denmark)

    Wang, Haojie; Han, Minxiao; Han, Renke

    2018-01-01

    This paper proposes a decentralized current-sharing control strategy to endow fast transient response to paralleled DC-DC converters systems, such as DC microgrids or distributed power systems. The proposed controller consist of two main control loops: an external voltage droop control for current......-sharing proposes and an internal current loop. The external droop control loop is designed as a voltage loop with embedded virtual impedance, which avoids the use of a slow voltage loop and a separate extra virtual impedance loop that may limit the system bandwidth. The internal current loop, thanks...... and the proposed embedded-virtual-impedance based I-V droop. In order to compare the dynamic response performances between two droop controllers, their state-space models have been developed and analyzed in this paper. The results show that the dynamic response of the I-V droop control is faster than...

  3. Transient temperature response of in-vessel components due to pulsed operation in tokamak fusion experimental reactor (FER)

    International Nuclear Information System (INIS)

    Minato, Akio; Tone, Tatsuzo

    1985-12-01

    A transient temperature response of the in-vessel components (first wall, blanket, divertor/limiter and shielding) surrounding plasma in Tokamak Fusion Experimental Reactor (FER) has been analysed. Transient heat load during start up/shut down and pulsed operation cycles causes the transient temperature response in those components. The fatigue lifetime of those components significantly depends upon the resulting cyclic thermal stress. The burn time affects the temperature control in the solid breeder (Li 2 O) and also affects the thermo-mechanical design of the blanket and shielding which are constructed with thick structure. In this report, results of the transient temperature response obtained by the heat transfer and conduction analyses for various pulsed operation scenarios (start up, shut down, burn and dwell times) have been investigated in view of thermo-mechanical design of the in-vessel components. (author)

  4. Differential response to dexamethasone on the TXB2 release in guinea-pig alveolar macrophages induced by zymosan and cytokines

    Directory of Open Access Journals (Sweden)

    M. E. Salgueiro

    1997-01-01

    Full Text Available Glucocorticosteroids reduce the production of inflammatory mediators but this effect may depend on the stimulus. We have compared the time course of the effect of dexamethasone on the thromboxane B2 (TXB2 release induced by cytokine stimulation and zymosan in guinea-pig alveolar macrophages. Interleukin-1β (IL-1β, tumour necrosis factor-α (TNF-α and opsonized zymosan (OZ, all stimulate TXB2 release. High concentrations of dexamethasone (1–10 μM inhibit the TXB2 production induced by both cytokines and OZ, but the time course of this response is different. Four hours of incubation with dexamethasone reduce the basal TXB2 release and that induced by IL-1β and TNF-α, but do not modify the TXB2 release induced by OZ. However, this stimulus was reduced after 24 h incubation. Our results suggest that the antiinflammatory activity of glucocorticosteroids shows some dependence on stimulus and, therefore, may have more than one mechanism involved.

  5. Variability in tuberculosis granuloma T cell responses exists, but a balance of pro- and anti-inflammatory cytokines is associated with sterilization.

    Directory of Open Access Journals (Sweden)

    Hannah Priyadarshini Gideon

    2015-01-01

    Full Text Available Lung granulomas are the pathologic hallmark of tuberculosis (TB. T cells are a major cellular component of TB lung granulomas and are known to play an important role in containment of Mycobacterium tuberculosis (Mtb infection. We used cynomolgus macaques, a non-human primate model that recapitulates human TB with clinically active disease, latent infection or early infection, to understand functional characteristics and dynamics of T cells in individual granulomas. We sought to correlate T cell cytokine response and bacterial burden of each granuloma, as well as granuloma and systemic responses in individual animals. Our results support that each granuloma within an individual host is independent with respect to total cell numbers, proportion of T cells, pattern of cytokine response, and bacterial burden. The spectrum of these components overlaps greatly amongst animals with different clinical status, indicating that a diversity of granulomas exists within an individual host. On average only about 8% of T cells from granulomas respond with cytokine production after stimulation with Mtb specific antigens, and few "multi-functional" T cells were observed. However, granulomas were found to be "multi-functional" with respect to the combinations of functional T cells that were identified among lesions from individual animals. Although the responses generally overlapped, sterile granulomas had modestly higher frequencies of T cells making IL-17, TNF and any of T-1 (IFN-γ, IL-2, or TNF and/or T-17 (IL-17 cytokines than non-sterile granulomas. An inverse correlation was observed between bacterial burden with TNF and T-1/T-17 responses in individual granulomas, and a combinatorial analysis of pair-wise cytokine responses indicated that granulomas with T cells producing both pro- and anti-inflammatory cytokines (e.g. IL-10 and IL-17 were associated with clearance of Mtb. Preliminary evaluation suggests that systemic responses in the blood do not

  6. Transient response of a cylindrical cavity in viscoelastic saturated porous medium

    Directory of Open Access Journals (Sweden)

    LIU Tao

    2016-10-01

    Full Text Available The study on dynamic characteristics for fluid-solid coupling system in saturated porous medium is of significant academic value and potential application foreground.In this paper,the transient response of a cylindrical cavity in infinite viscoelastic saturated porous medium with the circular lining is studied,and the corresponding results can be used in the design of foundation engineering,such as the tunnel analyses in saturated soil,the nuclear waste disposal engineering,and the exploitation and utilization of geothermal reservoirs and so on.Firstly,based on the porous media theory,the governing equations of coupled system are presented,and the corresponding boundary conditions,initial conditions as well as the joint conditions are derived.Then,the differential quadrature element method and the second-order backward difference scheme are applied to discretize the governing differential equations of the coupled system on the spatial and temporal domains,respectively.Finally,the Newton-Raphson method is adopted to solve the discretization equations with the initial conditions,the transient responses of the coupled system are analyzed,the effects of the parameters are considered,and the validity of the numerical method is verified.

  7. IL-33-induced alterations in murine intestinal function and cytokine responses are MyD88, STAT6, and IL-13-dependent

    Science.gov (United States)

    IL-33 is a recently identified cytokine member of the IL-1 family. The biological activities of IL-33 are associated with promotion of Th2 and inhibition of Th1/Th17 immune responses. Exogenous IL-33 induces a typical “type 2” immune response in the gastrointestinal tract, yet the underlying mechani...

  8. Sex differences in the pro-inflammatory cytokine response to endotoxin unfold in vivo but not ex vivo in healthy humans.

    Science.gov (United States)

    Wegner, Alexander; Benson, Sven; Rebernik, Laura; Spreitzer, Ingo; Jäger, Marcus; Schedlowski, Manfred; Elsenbruch, Sigrid; Engler, Harald

    2017-07-01

    Clinical data indicate that inflammatory responses differ across sexes, but the mechanisms remain elusive. Herein, we assessed in vivo and ex vivo cytokine responses to bacterial endotoxin in healthy men and women to elucidate the role of systemic and cellular factors underlying sex differences in inflammatory responses. Participants received an i.v. injection of low-dose endotoxin (0.4 ng/kg body mass), and plasma TNF-α and IL-6 responses were analyzed over a period of 6 h. In parallel, ex vivo cytokine production was measured in endotoxin-stimulated blood samples obtained immediately before in vivo endotoxin administration. As glucocorticoids (GCs) play an important role in the negative feedback regulation of the inflammatory response, we additionally analyzed plasma cortisol concentrations and ex vivo GC sensitivity of cytokine production. Results revealed greater in vivo pro-inflammatory responses in women compared with men, with significantly higher increases in plasma TNF-α and IL-6 concentrations. In addition, the endotoxin-induced rise in plasma cortisol was more pronounced in women. In contrast, no sex differences in ex vivo cytokine production and GC sensitivity were observed. Together, these findings demonstrate major differences in in vivo and ex vivo responses to endotoxin and underscore the importance of systemic factors underlying sex differences in the inflammatory response.

  9. Osteoarthritis and rheumatoid arthritis pannus have similar qualitative metabolic characteristics and pro-inflammatory cytokine response.

    Science.gov (United States)

    Furuzawa-Carballeda, J; Macip-Rodríguez, P M; Cabral, A R

    2008-01-01

    Pannus in osteoarthritis (OA) has only recently been characterized. Little is known, however, regarding the behavior of OA pannus in vitro compared to rheumatoid arthritis (RA) pannus. The purpose of our study was to compare OA with RA pannus. Pannus and synovial tissue co-cultures from 5 patients with OA and 5 patients with RA obtained during arthroplasty were studied. Pannus was defined as the microscopic invasive granulation tissue covering the articular surface. Tissues were cultured for 7 days and stained with Alcian Blue technique. Interleukin-1beta (IL-1beta), IL-8, IL-10, IL-12, tumor necrosis factor-alpha (TNF-alpha), and interferon gamma (IFN-gamma) were also determined in supernatants by ELISA. Cartilage oligomeric matrix protein (COMP), type II collagen, TNF-alpha, IL-10 and Ki-67 expression were also detected by immunohistochemistry. All patients had vascular or fibrous pannus. Synovial proliferation, inflammatory infiltrates and a decrease of extracellular matrix proteins were observed in all tissue samples. Chondrocyte proliferation was lower in OA than RA cartilage. OA synovial tissue expressed lower levels of proteoglycans than RA synoyium. Type II collagen levels were lower in OA than in RA cartilage. Significantly higher levels of IL-1beta were found in the supernatants of RA pannus compared to OA pannus (ppannus supernatants. IL-10, IL-12 and IFN-gamma were undetectable. RA and OA pannus had similar pro-inflammatory and anti-inflammatory cytokine profile expression. OA cartilage, synovial tissue and pannus had lower production of proteoglycans, type II collagen and IL-1beta. It remains to be elucidated why OA pannus invades the cartilage surface but does not cause the marginal erosions typically seen in RA.

  10. A simplified model for equilibrium and transient swelling of thermo-responsive gels.

    Science.gov (United States)

    Drozdov, A D; deClaville Christiansen, J

    2017-11-01

    A simplified model is developed for the elastic response of thermo-responsive gels subjected to swelling under an arbitrary deformation with finite strains. The constitutive equations involve five adjustable parameters that are determined by fitting observations in equilibrium water uptake tests and T-jump transient tests on thin gel disks. Two scenarios for water release under heating are revealed by means of numerical simulation. When the final temperature in a T-jump test is below the volume-phase transition temperature, deswelling is characterized by smooth distribution of water molecules and small tensile stresses. When the final temperature exceeds the critical temperature, a gel disk is split into three regions (central part with a high concentration of water molecules and two domains near the boundaries with low water content) separated by sharp interfaces, whose propagation is accompanied by development of large (comparable with the elastic modulus) tensile stresses. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. Immune response to snake envenoming and treatment with antivenom; complement activation, cytokine production and mast cell degranulation.

    Directory of Open Access Journals (Sweden)

    Shelley F Stone

    Full Text Available BACKGROUND: Snake bite is one of the most neglected public health issues in poor rural communities worldwide. In addition to the clinical effects of envenoming, treatment with antivenom frequently causes serious adverse reactions, including hypersensitivity reactions (including anaphylaxis and pyrogenic reactions. We aimed to investigate the immune responses to Sri Lankan snake envenoming (predominantly by Russell's viper and antivenom treatment. METHODOLOGY/PRINCIPAL FINDINGS: Plasma concentrations of Interleukin (IL-6, IL-10, tumor necrosis factor α (TNFα, soluble TNF receptor I (sTNFRI, anaphylatoxins (C3a, C4a, C5a; markers of complement activation, mast cell tryptase (MCT, and histamine were measured in 120 Sri Lankan snakebite victims, both before and after treatment with antivenom. Immune mediator concentrations were correlated with envenoming features and the severity of antivenom-induced reactions including anaphylaxis. Envenoming was associated with complement activation and increased cytokine concentrations prior to antivenom administration, which correlated with non-specific systemic symptoms of envenoming but not with coagulopathy or neurotoxicity. Typical hypersensitivity reactions to antivenom occurred in 77/120 patients (64%, satisfying criteria for a diagnosis of anaphylaxis in 57/120 (48%. Pyrogenic reactions were observed in 32/120 patients (27%. All patients had further elevations in cytokine concentrations, but not complement activation, after the administration of antivenom, whether a reaction was noted to occur or not. Patients with anaphylaxis had significantly elevated concentrations of MCT and histamine. CONCLUSIONS/SIGNIFICANCE: We have demonstrated that Sri Lankan snake envenoming is characterized by significant complement activation and release of inflammatory mediators. Antivenom treatment further enhances the release of inflammatory mediators in all patients, with anaphylactic reactions characterised by high

  12. Cytokine responses to novel antigens in an Indian population living in an area endemic for visceral leishmaniasis.

    Science.gov (United States)

    Singh, Om Prakash; Stober, Carmel B; Singh, Abhishek Kr; Blackwell, Jenefer M; Sundar, Shyam

    2012-01-01

    There are no effective vaccines for visceral leishmaniasis (VL), a neglected parasitic disease second only to malaria in global mortality. We previously identified 14 protective candidates in a screen of 100 Leishmania antigens as DNA vaccines in mice. Here we employ whole blood assays to evaluate human cytokine responses to 11 of these antigens, in comparison to known defined and crude antigen preparations. Whole blood assays were employed to measure IFN-γ, TNF-α and IL-10 responses to peptide pools of the novel antigens R71, Q51, L37, N52, L302.06, J89, M18, J41, M22, M63, M57, as well as to recombinant proteins of tryparedoxin peroxidase (TRYP), Leishmania homolog of the receptor for activated C kinase (LACK) and to crude soluble Leishmania antigen (SLA), in Indian patients with active (n = 8) or cured (n = 16) VL, and in modified Quantiferon positive (EHC(+ve), n = 20) or modified Quantiferon negative (EHC(-ve), n = 9) endemic healthy controls (EHC). Active VL, cured VL and EHC(+ve) groups showed elevated SLA-specific IFN-γ, but only active VL patients produced IL-10 and EHC(+ve) did not make TNF-α. IFN-γ to IL-10 and TNF-α to IL-10 ratios in response to TRYP and LACK antigens were higher in cured VL and EHC(+ve) exposed individuals compared to active VL. Five of the eleven novel candidates (R71, L37, N52, J41, and M22) elicited IFN-γ and TNF-α, but not IL-10, responses in cured VL (55-87.5% responders) and EHC(+ve) (40-65% responders) subjects. Our results are consistent with an important balance between pro-inflammatory IFNγ and TNFγ cytokine responses and anti-inflammatory IL-10 in determining outcome of VL in India, as highlighted by response to both crude and defined protein antigens. Importantly, cured VL patients and endemic Quantiferon positive individuals recognise 5 novel vaccine candidate antigens, confirming our recent data for L. chagasi in Brazil, and their potential as cross-species vaccine candidates.

  13. Cytokine responses to novel antigens in an Indian population living in an area endemic for visceral leishmaniasis.

    Directory of Open Access Journals (Sweden)

    Om Prakash Singh

    Full Text Available There are no effective vaccines for visceral leishmaniasis (VL, a neglected parasitic disease second only to malaria in global mortality. We previously identified 14 protective candidates in a screen of 100 Leishmania antigens as DNA vaccines in mice. Here we employ whole blood assays to evaluate human cytokine responses to 11 of these antigens, in comparison to known defined and crude antigen preparations.Whole blood assays were employed to measure IFN-γ, TNF-α and IL-10 responses to peptide pools of the novel antigens R71, Q51, L37, N52, L302.06, J89, M18, J41, M22, M63, M57, as well as to recombinant proteins of tryparedoxin peroxidase (TRYP, Leishmania homolog of the receptor for activated C kinase (LACK and to crude soluble Leishmania antigen (SLA, in Indian patients with active (n = 8 or cured (n = 16 VL, and in modified Quantiferon positive (EHC(+ve, n = 20 or modified Quantiferon negative (EHC(-ve, n = 9 endemic healthy controls (EHC.Active VL, cured VL and EHC(+ve groups showed elevated SLA-specific IFN-γ, but only active VL patients produced IL-10 and EHC(+ve did not make TNF-α. IFN-γ to IL-10 and TNF-α to IL-10 ratios in response to TRYP and LACK antigens were higher in cured VL and EHC(+ve exposed individuals compared to active VL. Five of the eleven novel candidates (R71, L37, N52, J41, and M22 elicited IFN-γ and TNF-α, but not IL-10, responses in cured VL (55-87.5% responders and EHC(+ve (40-65% responders subjects.Our results are consistent with an important balance between pro-inflammatory IFNγ and TNFγ cytokine responses and anti-inflammatory IL-10 in determining outcome of VL in India, as highlighted by response to both crude and defined protein antigens. Importantly, cured VL patients and endemic Quantiferon positive individuals recognise 5 novel vaccine candidate antigens, confirming our recent data for L. chagasi in Brazil, and their potential as cross-species vaccine candidates.

  14. Amino acid substitutions in the melanoma antigen recognized by T cell 1 peptide modulate cytokine responses in melanoma-specific T cells

    DEFF Research Database (Denmark)

    Nielsen, M B; Kirkin, A F; Loftus, D

    2000-01-01

    enhances the production of mRNA for interleukin (IL)-5, IL-10, IL-13, IL-15, and interferon-gamma and significantly enhances release of IL-13 and IL-10 from anti-MART-1 cytotoxic T cells. Another heteroclitic peptide, 1L, with an A to L substitution in MART-1(27-35), also enhances the tyrosine...... phosphorylation response in anti-MART-1 cytotoxic CD8+ T cells. Yet, 1L does not enhance the production of T helper cell type 2-like cytokines (IL-10 and IL-13). Together these data show that minor amino acid modifications of immunodominant melanoma peptides profoundly influence the cytokine response in melanoma...

  15. Plasma cytokines, chemokines and cellular immune responses in pre-school Nigerian children infected with Plasmodium falciparum

    Directory of Open Access Journals (Sweden)

    Noone Cariosa

    2013-01-01

    Full Text Available Abstract Background Malaria is a major cause of morbidity and mortality worldwide with over one million deaths annually, particularly in children under five years. This study was the first to examine plasma cytokines, chemokines and cellular immune responses in pre-school Nigerian children infected with Plasmodium falciparum from four semi-urban villages near Ile-Ife, Osun State, Nigeria. Methods Blood was obtained from 231 children (aged 39–73 months who were classified according to mean P. falciparum density per μl of blood (uninfected (n = 89, low density (10,000, n = 22. IL-12p70, IL-10, Nitric oxide, IFN-γ, TNF, IL-17, IL-4 and TGF-β, C-C chemokine RANTES, MMP-8 and TIMP-1 were measured in plasma. Peripheral blood mononuclear cells were obtained and examined markers of innate immune cells (CD14, CD36, CD56, CD54, CD11c AND HLA-DR. T-cell sub-populations (CD4, CD3 and γδTCR were intracellularly stained for IL-10, IFN-γ and TNF following polyclonal stimulation or stimulated with malaria parasites. Ascaris lumbricoides was endemic in these villages and all data were analysed taking into account the potential impact of bystander helminth infection. All data were analysed using SPSS 15 for windows and in all tests, p Results The level of P. falciparum parasitaemia was positively associated with plasma IL-10 and negatively associated with IL-12p70. The percentage of monocytes was significantly decreased in malaria-infected individuals while malaria parasitaemia was positively associated with increasing percentages of CD54+, CD11c+ and CD56+ cell populations. No association was observed in cytokine expression in mitogen-activated T-cell populations between groups and no malaria specific immune responses were detected. Although A. lumbricoides is endemic in these villages, an analysis of the data showed no impact of this helminth infection on P. falciparum parasitaemia or on immune responses associated with P. falciparum infection

  16. Transient radiation responses of optical fibers: influence of MCVD process parameters

    International Nuclear Information System (INIS)

    Girard, Sylvain; Alessi, Antonino; Boukenter, Aziz; Ouerdane, Y.; Marcandella, Claude; Richard, Nicolas; Paillet, Philippe; Gaillardin, Marc; Raine, Melanie

    2012-01-01

    A dedicated set of fibers elaborated via the Modified Chemical Vapor Deposition (MCVD) technique is used to study the influence of composition and drawing parameters on their responses to an X-ray pulse representative of the radiation environments associated with Megajoule class lasers. These canonical fibers were designed to highlight the impact of these parameters on the amplitude and kinetics of the transient pulsed X-ray Radiation Induced Attenuation (RIA) at room temperature. From pre-forms differing by their core composition, three optical fibers were elaborated by varying the tension and speed during the drawing process. No or only slight RIA change results from the tested variations in drawing process parameters of Ge-doped, F-doped, and pure-silica-core fibers. This study reveals that the drawing process is not the main parameter to be optimized in order to enhance the radiation tolerance of MCVD specialty optical fibers for the LMJ harsh environment. From the hardness assurance point of view, a specialty fiber sufficiently tolerant to this environment should be robust against changes in the drawing process. The origins of the RIA observed in the different fibers are discussed on the basis of spectral decomposition of their measured RIA spectra, using sets of defects from the literature and related to the different core dopants. This analysis highlights the limits of the well-known defect set to reproduce the RIA above 1 for Ge-doped fibers whereas self-trapped holes and chlorine-related species seem responsible for the transient responses of pure-silica-core and F-doped fibers. (authors)

  17. Transient response of a polymer electrolyte membrane fuel cell subjected to time-varying modulating conditions

    Energy Technology Data Exchange (ETDEWEB)

    Noorani, S.; Shamim, T. [Michigan-Dearborn Univ., Dearborn, MI (United States). Dept. of Mechanical Engineering

    2009-07-01

    In order for fuel cells to compete with internal combustion engines, they must have significant advantages in terms of overall efficiency, weight, packaging, safety and cost. A key requirement is its ability to operate under highly transient conditions during start-up, acceleration, and deceleration with stable performance. Therefore, a better understanding of fuel cell dynamic behaviour is needed along with better water management and distributions inside the cell. Therefore, this study investigated the effect of transient conditions on water distribution inside a polymer electrolyte membrane (PEM) cell. A macroscopic single-fuel cell based, one-dimensional, isothermal mathematical model was used to study the effect of modulating cell voltage on the water distribution of anode, cathode, catalyst layers, and membrane. Compared to other existing models, this model did not rely on the non-physical assumption of the uptake curve equilibrium between the pore vapour and ionomer water in the catalyst layers. Instead, the transition between the two phases was modeled as a finite-rate equilibration process. The modulating conditions were simulated by forcing the temporal variations in fuel cell voltage. The results revealed that cell voltage modulations cause a departure in the cell behaviour from its steady behaviour, and the finite-rate equilibration between the catalyst vapour and liquid water can be a factor in determining the cell response. The cell response is also affected by the modulating frequency and amplitude. The peak cell response was observed at low frequencies. Keywords: fuel cell, water transport, dynamic behaviour, numerical simulations. 9 refs., 1 tab., 5 figs.

  18. Energetic and metabolic transient response of Saccharomyces cerevisiae to benzoic acid.

    Science.gov (United States)

    Kresnowati, M T A P; van Winden, W A; van Gulik, W M; Heijnen, J J

    2008-11-01

    Saccharomyces cerevisiae is known to be able to adapt to the presence of the commonly used food preservative benzoic acid with a large energy expenditure. Some mechanisms for the adaptation process have been suggested, but its quantitative energetic and metabolic aspects have rarely been discussed. This study discusses use of the stimulus response approach to quantitatively study the energetic and metabolic aspects of the transient adaptation of S. cerevisiae to a shift in benzoic acid concentration, from 0 to 0.8 mM. The information obtained also serves as the basis for further utilization of benzoic acid as a tool for targeted perturbation of the energy system, which is important in studying the kinetics and regulation of central carbon metabolism in S. cerevisiae. Using this experimental set-up, we found significant fast-transient (< 3000 s) increases in O(2) consumption and CO(2) production rates, of approximately 50%, which reflect a high energy requirement for the adaptation process. We also found that with a longer exposure time to benzoic acid, S. cerevisiae decreases the cell membrane permeability for this weak acid by a factor of 10 and decreases the cell size to approximately 80% of the initial value. The intracellular metabolite profile in the new steady-state indicates increases in the glycolytic and tricarboxylic acid cycle fluxes, which are in agreement with the observed increases in specific glucose and O(2) uptake rates.

  19. Transient response of rotating laminated functionally graded cylindrical shells in thermal environment

    International Nuclear Information System (INIS)

    Malekzadeh, P.; Heydarpour, Y.; Haghighi, M.R. Golbahar; Vaghefi, M.

    2012-01-01

    Based on the elasticity theory, the transient analysis of dynamically pressurized rotating multi-layered functionally graded (FG) cylindrical shells in thermal environment is presented. The variations of the field variables across the shell thickness are accurately modeled by dividing the shell into a set of co-axial mathematical layers in the radial direction. The initial thermo-mechanical stresses are obtained by solving the thermoelastic equilibrium equations. The differential quadrature method and Newmark's time integration scheme are employed to discretize the obtained governing equations of each mathematical layer. After performing the convergence and comparison studies, parametric studies for two common types of FG sandwich shells, namely, the shell with homogeneous inner/outer layers and FG core and the shell with FG inner/outer layers and homogeneous core are carried out. The influences of the temperature dependence of material properties, material graded index, the convective heat transfer coefficient, the angular velocity, the boundary condition and the geometrical parameters (length and thickness to outer radius ratios) on the dynamic response of the FG shells are investigated. Highlights: ► As a first endeavor, transient analysis of rotating laminated functionally graded cylinders. ► Employing an elasticity based discrete layer-differential quadrature method. ► Evaluating and including the initial thermo-mechanical stresses accurately. ► Considering the temperature-dependence of the material properties. ► Presenting some new results, which can be used as benchmark solution for future works.

  20. Myxovirus resistance, osteopontin and suppressor of cytokine signaling 3 polymorphisms predict hepatitis C virus therapy response in an admixed patient population: comparison with IL28B.

    Science.gov (United States)

    Angelo, Ana Luiza Dias; Cavalcante, Lourianne Nascimento; Abe-Sandes, Kiyoko; Machado, Taísa Bonfim; Lemaire, Denise Carneiro; Malta, Fernanda; Pinho, João Renato; Lyra, Luiz Guilherme Costa; Lyra, Andre Castro

    2013-10-01

    Suppressor of cytokine signaling 3, myxovirus resistance protein and osteopontin gene polymorphisms may influence the therapeutic response in patients with chronic hepatitis C, and an association with IL28 might increase the power to predict sustained virologic response. Our aims were to evaluate the association between myxovirus resistance protein, osteopontin and suppressor of cytokine signaling 3 gene polymorphisms in combination with IL28B and to assess the therapy response in hepatitis C patients treated with pegylated-interferon plus ribavirin. Myxovirus resistance protein, osteopontin, suppressor of cytokine signaling 3 and IL28B polymorphisms were analyzed by PCR-restriction fragment length polymorphism, direct sequencing and real-time PCR. Ancestry was determined using genetic markers. We analyzed 181 individuals, including 52 who were sustained virologic responders. The protective genotype frequencies among the sustained virologic response group were as follows: the G/G suppressor of cytokine signaling 3 (rs4969170) (62.2%); T/T osteopontin (rs2853744) (60%); T/T osteopontin (rs11730582) (64.3%); and the G/T myxovirus resistance protein (rs2071430) genotype (54%). The patients who had ≥3 of the protective genotypes from the myxovirus resistance protein, the suppressor of cytokine signaling 3 and osteopontin had a greater than 90% probability of achieving a sustained response (pC/C IL28B genotype was present in 58.8% of the subjects in this group. The sustained virological response rates increased to 85.7% and 91.7% by analyzing C/C IL28B with the T/T osteopontin genotype at rs11730582 and the G/G suppressor of cytokine signaling 3 genotype, respectively. Genetic ancestry analysis revealed an admixed population. Hepatitis C genotype 1 patients who were responders to interferon-based therapy had a high frequency of multiple protective polymorphisms in the myxovirus resistance protein, osteopontin and suppressor of cytokine signaling 3 genes. The combined

  1. Experimental studies on thermal hydraulic responses for transient operations of the SMART-P

    International Nuclear Information System (INIS)

    Choi, K.Y.; Park, H.S.; Cho, S.; Park, C.K.; Lee, S.J.; Song, C.H.; Chung, M.K.

    2005-01-01

    Full text of publication follows: Thermal hydraulic responses for transient operations of the SMART-P are experimentally investigated by using a integral effect test facility. This test facility (VISTA) has been constructed to simulate the SMART-P, which is a pilot plant of the SMART. The SMART-P is an advanced modular integral type pressurized water reactor (65 MWt) whose major RCS components, such as main coolant pumps, helical-coiled tube bundle steam generators and pressurizers, are contained in a reactor vessel. This integral design approach eliminates the large coolant loop piping, thus eliminates the occurrence of a large break LOCA. Passive Residual Heat Removal System (PRHRS) is installed to prevent overheating and over-pressurization of the primary system during accidental conditions. The PRHRS of the SMART-P removes the core decay heat by natural circulation of the two-phase fluid. The VISTA facility is a full height and 1/96 volume scaled test facility with respect to the SMART-P and will be used to understand the thermal-hydraulic responses following transients and finally to verify the system design of the SMART-P. The experimental data from the VISTA facility will be essential to system designers to resolve open issues relevant to the design of the SMART-P. The full functional control logics are implanted into the VISTA facility to cope with abnormal transients. The core of the facility can be selectively controlled by either a T-control or a T+N control method. The T-control method is a control method to adjust the core power according to the core exit coolant temperature and is designed to be used for high primary coolant flow conditions. On the other hand, the T+N control method is for low primary coolant flow conditions and it uses core exit temperature as well as core power itself as control inputs. The thermal hydraulic responses are carefully investigated according to different core control methods. Several experiments have been performed to

  2. The effects of air stoichiometry and air excess ratio on the transient response of a PEMFC under load change conditions

    International Nuclear Information System (INIS)

    Kim, Bosung; Cha, Dowon; Kim, Yongchan

    2015-01-01

    Highlights: • Effects of controlling parameters on the transient response of a PEMFC are studied. • The transient response is measured by varying air stoichiometry and air excess ratio. • Voltage drop, undershoot, and voltage fluctuation are analyzed under the load change. • Optimal air stoichiometry and air excess ratio are suggested for stable operation. - Abstract: The transient response of a proton exchange membrane fuel cell (PEMFC) is an important issue for transportation applications. The objective of this study is to investigate the effects of operating and controlling parameters on the transient response of a PEMFC for achieving more stable cell performance under load change conditions. The transient response of a PEMFC was measured and analyzed by varying air stoichiometry, air humidity, and air excess ratio (AER). The optimal air stoichiometry and AER were determined to minimize the voltage drop, undershoot, and voltage fluctuation under the load change, while maintaining high cell performance. Based on the present data, the optimal air stoichiometry was determined to be between 2.0 and 2.5, and the optimal AER was suggested to be between 1.65 and 2.0

  3. Inflammatory cytokines in the brain: does the CNS shape immune responses?

    Science.gov (United States)

    Owens, T; Renno, T; Taupin, V; Krakowski, M

    1994-12-01

    Immune responses in the central nervous system (CNS) have traditionally been regarded as representing the intrusion of an unruly, ill-behaved mob of leukocytes into the well-ordered and organized domain of thought and reason. However, results accumulated over the past few years suggest that, far from being an immunologically privileged organ, T lymphocytes may be regular and frequent visitors to the CNS, for purposes of immune surveillance. Here, Trevor Owens and colleagues propose that the brain itself can regulate or shape immune responses therein. Furthermore, given that the immune cells may be subverted to autoimmunity, they suggest that the study of inflammatory autoimmune disease in the brain may shed light on the ability of the local environment to regulate immune responses.

  4. Association of CD30 transcripts with Th1 responses and proinflammatory cytokines in patients with end-stage renal disease.

    Science.gov (United States)

    Velásquez, Sonia Y; Opelz, Gerhard; Rojas, Mauricio; Süsal, Caner; Alvarez, Cristiam M

    2016-05-01

    High serum sCD30 levels are associated with inflammatory disorders and poor outcome in renal transplantation. The contribution to these phenomena of transcripts and proteins related to CD30-activation and -cleavage is unknown. We assessed in peripheral blood of end-stage renal disease patients (ESRDP) transcripts of CD30-activation proteins CD30 and CD30L, CD30-cleavage proteins ADAM10 and ADAM17, and Th1- and Th2-type immunity-related factors t-bet and GATA3. Additionally, we evaluated the same transcripts and release of sCD30 and 32 cytokines after allogeneic and polyclonal T-cell activation. In peripheral blood, ESRDP showed increased levels of t-bet and GATA3 transcripts compared to healthy controls (HC) (both PCD30, CD30L, ADAM10 and ADAM17 transcripts were similar. Polyclonal and allogeneic stimulation induced higher levels of CD30 transcripts in ESRDP than in HC (both PsCD30, the Th-1 cytokine IFN-γ, MIP-1α, RANTES, sIL-2Rα, MIP-1β, TNF-β, MDC, GM-CSF and IL-5, and another one consisting of CD30 and t-bet transcripts, IL-13 and proinflammatory proteins IP-10, IL-8, IL-1Rα and MCP-1. Reflecting an activated immune state, ESRDP exhibited after allostimulation upregulation of CD30 transcripts in T cells, which was associated with Th1 and proinflammatory responses. Copyright © 2016 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

  5. Effects of Acute Endurance Exercise Performed in the Morning and Evening on Inflammatory Cytokine and Metabolic Hormone Responses.

    Directory of Open Access Journals (Sweden)

    Hyeon-Ki Kim

    Full Text Available To compare the effects of endurance exercise performed in the morning and evening on inflammatory cytokine responses in young men.Fourteen healthy male participants aged 24.3 ± 0.8 years (mean ± standard error performed endurance exercise in the morning (0900-1000 h on one day and then in the evening (1700-1800 h on another day with an interval of at least 1 week between each trial. In both the morning and evening trials, the participants walked for 60 minutes at approximately 60% of the maximal oxygen uptake (VO2max on a treadmill. Blood samples were collected to determine hormones and inflammatory cytokines at pre-exercise, immediately post exercise, and 2 h post exercise.Plasma interleukin (IL-6 and adrenaline concentrations were significantly higher immediately after exercise in the evening trial than in the morning trial (P < 0.01, both. Serum free fatty acids concentrations were significantly higher in the evening trial than in the morning trial at 2 h after exercise (P < 0.05. Furthermore, a significant correlation was observed between the levels of IL-6 immediately post-exercise and free fatty acids 2 h post-exercise in the evening (r = 0.68, P < 0.01.These findings suggest that the effect of acute endurance exercise in the evening enhances the plasma IL-6 and adrenaline concentrations compared to that in the morning. In addition, IL-6 was involved in increasing free fatty acids, suggesting that the evening is more effective for exercise-induced lipolysis compared with the morning.

  6. CD4 T-helper cell cytokine phenotypes and antibody response following tetanus toxoid booster immunization

    Science.gov (United States)

    Routine methods for enumerating antigen-specific T-helper cells may not identify low-frequency phenotypes such as Th2 cells. We compared methods of evaluating such responses to identify tetanus toxoid- (TT) specific Th1, Th2, Th17 and IL10+ cells. Eight healthy subjects were given a TT booster vacci...

  7. Dissecting the T Cell Response: Proliferation Assays vs. Cytokine Signatures by ELISPOT

    Directory of Open Access Journals (Sweden)

    Magdalena Tary-Lehmann

    2012-05-01

    Full Text Available Chronic allograft rejection is in part mediated by host T cells that recognize allogeneic antigens on transplanted tissue. One factor that determines the outcome of a T cell response is clonal size, while another is the effector quality. Studies of alloimmune predictors of transplant graft survival have most commonly focused on only one measure of the alloimmune response. Because differing qualities and frequencies of the allospecific T cell response may provide distinctly different information we analyzed the relationship between frequency of soluble antigen and allo-antigen specific memory IFN-g secreting CD4 and CD8 T cells, their ability to secrete IL-2, and their proliferative capacity, while accounting for cognate and bystander proliferation. The results show proliferative responses primarily reflect on IL-2 production by antigen-specific T cells, and that proliferating cells in such assays entail a considerable fraction of bystander cells. On the other hand, proliferation (and IL-2 production did not reflect on the frequency of IFN-γ producing memory cells, a finding particularly accentuated in the CD8 T cell compartment. These data provide rationale for considering both frequency and effector function of pre-transplant T cell reactivity when analyzing immune predictors of graft rejection.

  8. Dissecting the T Cell Response: Proliferation Assays vs. Cytokine Signatures by ELISPOT

    Science.gov (United States)

    Anthony, Donald D.; Milkovich, Kimberly A.; Zhang, Wenji; Rodriguez, Benigno; Yonkers, Nicole L.; Tary-Lehmann, Magdalena; Lehmann, Paul V.

    2012-01-01

    Chronic allograft rejection is in part mediated by host T cells that recognize allogeneic antigens on transplanted tissue. One factor that determines the outcome of a T cell response is clonal size, while another is the effector quality. Studies of alloimmune predictors of transplant graft survival have most commonly focused on only one measure of the alloimmune response. Because differing qualities and frequencies of the allospecific T cell response may provide distinctly different information we analyzed the relationship between frequency of soluble antigen and allo-antigen specific memory IFN-γ secreting CD4 and CD8 T cells, their ability to secrete IL-2, and their proliferative capacity, while accounting for cognate and bystander proliferation. The results show proliferative responses primarily reflect on IL-2 production by antigen-specific T cells, and that proliferating cells in such assays entail a considerable fraction of bystander cells. On the other hand, proliferation (and IL-2 production) did not reflect on the frequency of IFN-γ producing memory cells, a finding particularly accentuated in the CD8 T cell compartment. These data provide rationale for considering both frequency and effector function of pre-transplant T cell reactivity when analyzing immune predictors of graft rejection. PMID:24710419

  9. Inflammatory cytokines in the brain: does the CNS shape immune responses?

    DEFF Research Database (Denmark)

    Owens, T; Renno, T; Taupin, V

    1994-01-01

    Immune responses in the central nervous system (CNS) have traditionally been regarded as representing the intrusion of an unruly, ill-behaved mob of leukocytes into the well-ordered and organized domain of thought and reason. However, results accumulated over the past few years suggest that, far ...

  10. Identification of Lactobacillus plantarum genes modulating the cytokine response of human peripheral blood mononuclear cells

    NARCIS (Netherlands)

    van Hemert, Saskia; Meijerink, Marjolein; Molenaar, Douwe; Bron, Peter A.; de Vos, Paul; Kleerebezem, Michiel; Wells, Jerry M.; Marco, Maria L.

    2010-01-01

    Background: Modulation of the immune system is one of the most plausible mechanisms underlying the beneficial effects of probiotic bacteria on human health. Presently, the specific probiotic cell products responsible for immunomodulation are largely unknown. In this study, the genetic and phenotypic

  11. Antigen-Specific Interferon-Gamma Responses and Innate Cytokine Balance in TB-IRIS

    NARCIS (Netherlands)

    Goovaerts, Odin; Jennes, Wim; Massinga-Loembé, Marguerite; Ceulemans, Ann; Worodria, William; Mayanja-Kizza, Harriet; Colebunders, Robert; Kestens, Luc; Loembé, Marguerite Massinga; Mayanja, Harriet; Mascart, Francoise; van den Bergh, Rafael; Locht, Camille; Reiss, Peter; Cobelens, Frank; Ondoa, Pascale; Pakker, Nadine; Mugerwa, Roy

    2014-01-01

    Background: Tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) remains a poorly understood complication in HIV-TB patients receiving antiretroviral therapy (ART). TB-IRIS could be associated with an exaggerated immune response to TB-antigens. We compared the recovery of

  12. Acute and chronic cytokine responses to resistance exercise and training in people with multiple sclerosis

    DEFF Research Database (Denmark)

    Kjølhede, Tue; Dalgas, Ulrik; Brolin Gade, Anne

    2016-01-01

    Exercise is a well-established part of rehabilitation for people with multiple sclerosis (PwMS), and it has been hypothesized to stimulate an anti-inflammatory environment that might be disease modifying. Yet, investigations on exercise-induced immune responses are scarce and generally not paying...

  13. Transient Genome-Wide Transcriptional Response to Low-Dose Ionizing Radiation In Vivo in Humans

    International Nuclear Information System (INIS)

    Berglund, Susanne R.; Rocke, David M.; Dai Jian; Schwietert, Chad W.; Santana, Alison; Stern, Robin L.; Lehmann, Joerg; Hartmann Siantar, Christine L.; Goldberg, Zelanna

    2008-01-01

    Purpose: The in vivo effects of low-dose low linear energy transfer ionizing radiation on healthy human skin are largely unknown. Using a patient-based tissue acquisition protocol, we have performed a series of genomic analyses on the temporal dynamics over a 24-hour period to determine the radiation response after a single exposure of 10 cGy. Methods and Materials: RNA from each patient tissue sample was hybridized to an Affymetrix Human Genome U133 Plus 2.0 array. Data analysis was performed on selected gene groups and pathways. Results: Nineteen gene groups and seven gene pathways that had been shown to be radiation responsive were analyzed. Of these, nine gene groups showed significant transient transcriptional changes in the human tissue samples, which returned to baseline by 24 hours postexposure. Conclusions: Low doses of ionizing radiation on full-thickness human skin produce a definable temporal response out to 24 hours postexposure. Genes involved in DNA and tissue remodeling, cell cycle transition, and inflammation show statistically significant changes in expression, despite variability between patients. These data serve as a reference for the temporal dynamics of ionizing radiation response following low-dose exposure in healthy full-thickness human skin

  14. Pre-existing adenovirus immunity modifies a complex mixed Th1 and Th2 cytokine response to an Ad5/HIV-1 vaccine candidate in humans.

    Directory of Open Access Journals (Sweden)

    Samuel O Pine

    2011-04-01

    Full Text Available The results of the recent Step Study highlight a need to clarify the effects of pre-existing natural immunity to a vaccine vector on vaccine-induced T-cell responses. To investigate this interaction, we examined the relationship between pre-existing Ad5 immunity and T-cell cytokine response profiles in healthy, HIV-uninfected recipients of MRKAd5 HIV-1 gag vaccine (HVTN 050, ClinicalTrials.gov #NCT00849732. Participants were grouped by baseline Ad5 neutralizing antibody titer as either Ad5-seronegative (titer ≤18; n = 36 or Ad5-seropositive (titer >200; n = 34. Samples from vaccine recipients were analyzed for immune responses to either HIV-1 Gag peptide pools or Ad5 empty vector using an ex vivo assay that measures thirty cytokines in the absence of long-term culture. The overall profiles of cytokine responses to Gag and Ad5 had similar combinations of induced Th1- and Th2-type cytokines, including IFN-γ, IL-2, TNF-α, IP-10, IL-13, and IL-10, although the Ad5-specific responses were uniformly higher than the Gag-specific responses (p<0.0001 for 9 out of 11 significantly expressed analytes. At the peak response time point, PBMC from Ad5-seronegative vaccinees secreted significantly more IP-10 in response to Gag (p = 0.008, and significantly more IP-10 (p = 0.0009, IL-2 (p = 0.006 and IL-10 (p = 0.05 in response to Ad5 empty vector than PBMC from Ad5-seropositive vaccinees. Additionally, similar responses to the Ad5 vector prior to vaccination were observed in almost all subjects, regardless of Ad5 neutralizing antibody status, and the levels of secreted IFN-γ, IL-10, IL-1Ra and GM-CSF were blunted following vaccination. The cytokine response profile of Gag-specific T cells mirrored the Ad5-specific response present in all subjects before vaccination, and included a number of Th1- and Th2-associated cytokines not routinely assessed in current vaccine trials, such as IP-10, IL-10, IL-13, and GM-CSF. Together, these

  15. Evaluation of time integration methods for transient response analysis of nonlinear structures

    International Nuclear Information System (INIS)

    Park, K.C.

    1975-01-01

    Recent developments in the evaluation of direct time integration methods for the transient response analysis of nonlinear structures are presented. These developments, which are based on local stability considerations of an integrator, show that the interaction between temporal step size and nonlinearities of structural systems has a pronounced effect on both accuracy and stability of a given time integration method. The resulting evaluation technique is applied to a model nonlinear problem, in order to: 1) demonstrate that it eliminates the present costly process of evaluating time integrator for nonlinear structural systems via extensive numerical experiments; 2) identify the desirable characteristics of time integration methods for nonlinear structural problems; 3) develop improved stiffly-stable methods for application to nonlinear structures. Extension of the methodology for examination of the interaction between a time integrator and the approximate treatment of nonlinearities (such as due to pseudo-force or incremental solution procedures) is also discussed. (Auth.)

  16. Transient response of a five-region nonequilibrium real-time pressurizer model

    International Nuclear Information System (INIS)

    Fakory, M.R.; Seifaee, F.

    1987-01-01

    Recent accidents at nuclear power plants in the US and abroad have prompted accurate analysis and simulation of the plant systems and the training of reactor operators on plant-specific simulators that are equipped with the simulation models. Consequently, several models for real-time and off-time simulation of nuclear reactor systems, with various levels of accuracy and simulation fidelity, have been introduced. Experience with power plant simulation demonstrates that in order to realistically predict and simulate reactor responses during unanticipated transients, it is necessary to equip the simulation model with a multielement pressurizer model. The objective of this paper is to present the results of a five-region drift-flux-based pressurizer model, which has been developed for integration with real-time training simulators. A comparison between the plant data and the results of the nonequilibrium pressurizer model demonstrates that the model is well capable of close simulation of dynamic behavior of the pressurizer system

  17. Analysis of pressure wave transients and seismic response in LMFBR piping systems using the SHAPS code

    International Nuclear Information System (INIS)

    Zeuch, W.R.; Wang, C.Y.

    1985-01-01

    This paper presents some of the current capabilities of the three-dimensional piping code SHAPS and demonstrates their usefulness in handling analyses encountered in typical LMFBR studies. Several examples demonstrate the utility of the SHAPS code for problems involving fluid-structure interactions and seismic-related events occurring in three-dimensional piping networks. Results of two studies of pressure wave propagation demonstrate the dynamic coupling of pipes and elbows producing global motion and rigorous treatment of physical quantities such as changes in density, pressure, and strain energy. Results of the seismic analysis demonstrate the capability of SHAPS to handle dynamic structural response within a piping network over an extended transient period of several seconds. Variation in dominant stress frequencies and global translational frequencies were easily handled with the code. 4 refs., 10 figs

  18. Transient response of a liquid injector to a steep-fronted transverse pressure wave

    Science.gov (United States)

    Lim, D.; Heister, S.; Stechmann, D.; Kan, B.

    2017-12-01

    Motivated by the dynamic injection environment posed by unsteady pressure gain combustion processes, an experimental apparatus was developed to visualize the dynamic response of a transparent liquid injector subjected to a single steep-fronted transverse pressure wave. Experiments were conducted at atmospheric pressure with a variety of acrylic injector passage designs using water as the working fluid. High-speed visual observations were made of the injector exit near field, and the extent of backflow and the time to refill the orifice passage were characterized over a range of injection pressures. A companion transient one-dimensional model was developed for interpretation of the results and to elucidate the trends with regard to the strength of the transverse pressure wave. Results from the model were compared with the experimental observations.

  19. Equivalent circuit simulation of HPEM-induced transient responses at nonlinear loads

    Directory of Open Access Journals (Sweden)

    M. Kotzev

    2017-09-01

    Full Text Available In this paper the equivalent circuit modeling of a nonlinearly loaded loop antenna and its transient responses to HPEM field excitations are investigated. For the circuit modeling the general strategy to characterize the nonlinearly loaded antenna by a linear and a nonlinear circuit part is pursued. The linear circuit part can be determined by standard methods of antenna theory and numerical field computation. The modeling of the nonlinear circuit part requires realistic circuit models of the nonlinear loads that are given by Schottky diodes. Combining both parts, appropriate circuit models are obtained and analyzed by means of a standard SPICE circuit simulator. It is the main result that in this way full-wave simulation results can be reproduced. Furthermore it is clearly seen that the equivalent circuit modeling offers considerable advantages with respect to computation speed and also leads to improved physical insights regarding the coupling between HPEM field excitation and nonlinearly loaded loop antenna.

  20. Application of response theory to steam venting during a loss of AC power transient

    Energy Technology Data Exchange (ETDEWEB)

    Cady, K.B.; Miller, R.J.

    1987-05-01

    We have applied the theory of response to the loss of AC power transient for an LMFBR design to determine the ultimate loss of coolant inventory and the sensitivity of this figure with respect to the initial conditions and input parameters. Using a simple four region heat transfer model, the analysis shows that 3717 kg coolant are vented after feed water is lost and before venting stops. The sensitivity analysis reveals that this figure is strongly dependent on design parameters and system assumptions. The uncertainty in the lost inventory caused by the uncertainties and correlations in the input parameters and initial conditions is found to be 3464 kg. We thus report the result of the calculation as lost inventory (kg)=3717+-3464 and conclude that the available inventory of 8775 kg is sufficient to ensure an adequate heat sink.

  1. Digitally Controlled Point of Load Converter with Very Fast Transient Response

    DEFF Research Database (Denmark)

    Jakobsen, Lars Tønnes; Andersen, Michael Andreas E.

    2007-01-01

    voltage mode control and very fast transient response. The DiSOM modulator is combined with a digital PID compensator algorithm is implemented in a hybrid CPLD/FPGA and is used to control a synchronous Buck converter, which is used in typical Point of Load applications. The computational time is only......This paper presents a new Digital Self-Oscillating Modulator (DiSOM) that allows the duty cycle to be changed instantly. The DiSOM modulator is shown to have variable switching that is a function of the duty cycle. Compared to a more traditional digital PWM modulator based on a counter...... and comparator the DiSOM modulator allows the sampling frequency of the output voltage control loop to be higher than the switching frequency of the power converter, typically a DC/DC converter. The features of the DiSOM modulator makes it possible to design a digitally controlled DC/DC converter with linear...

  2. Western Wind and Solar Integration Study Phase 3 – Frequency Response and Transient Stability

    Energy Technology Data Exchange (ETDEWEB)

    Miller, N. W. [GE Energy Management, Schenectady, NY (United States); Shao, M. [GE Energy Management, Schenectady, NY (United States); Pajic, S. [GE Energy Management, Schenectady, NY (United States); D' Aquila, R. [GE Energy Management, Schenectady, NY (United States)

    2014-12-01

    Power system operators and utilities worldwide have concerns about the impact of high-penetration wind and solar generation on electric grid reliability (EirGrid 2011b, Hydro-Quebec 2006, ERCOT 2010). The stability of North American grids under these conditions is a particular concern and possible impediment to reaching future renewable energy goals. Phase 3 of the Western Wind and Solar Integration Study (WWSIS-3) considers a 33% wind and solar annual energy penetration level that results in substantial changes to the characteristics of the bulk power system, including different power flow patterns, different commitment and dispatch of existing synchronous generation, and different dynamic behavior of wind and solar generation. WWSIS-3 evaluates two specific aspects of fundamental frequency system stability: frequency response and transient stability.

  3. Thermal-structural response of EBR-II major components under reactor operational transients

    International Nuclear Information System (INIS)

    Chang, L.K.; Lee, M.J.

    1983-01-01

    Until recently, the LMFBR safety research has been focused primarily on severe but highly unlikely accident, such as hypothetical-core-disruptive accidents (HCDA's), and not enough attention has been given to accident prevention, which is less severe but more likely sequence. The objective of the EBR-II operational reliability testing (ORT) is to demonstrate that the reactor can be designed and operated to prevent accident. A series of mild duty cycles and overpower transients were designed for accident prevention tests. An assessment of the EBR-II major plant components has been performed to assure structural integrity of the reactor plant for the ORT program. In this paper, the thermal-structural response and structural evaluation of the reactor vessel, the reactor-vessel cover, the intermediate heat exchanger (IHX) and the superheater are presented

  4. Hepcidin mediates transcriptional changes that modulate acute cytokine-induced inflammatory responses in mice.

    Science.gov (United States)

    De Domenico, Ivana; Zhang, Tian Y; Koening, Curry L; Branch, Ryan W; London, Nyall; Lo, Eric; Daynes, Raymond A; Kushner, James P; Li, Dean; Ward, Diane M; Kaplan, Jerry

    2010-07-01

    Hepcidin is a peptide hormone that regulates iron homeostasis and acts as an antimicrobial peptide. It is expressed and secreted by a variety of cell types in response to iron loading and inflammation. Hepcidin mediates iron homeostasis by binding to the iron exporter ferroportin, inducing its internalization and degradation via activation of the protein kinase Jak2 and the subsequent phosphorylation of ferroportin. Here we have shown that hepcidin-activated Jak2 also phosphorylates the transcription factor Stat3, resulting in a transcriptional response. Hepcidin treatment of ferroportin-expressing mouse macrophages showed changes in mRNA expression levels of a wide variety of genes. The changes in transcript levels for half of these genes were a direct effect of hepcidin, as shown by cycloheximide insensitivity, and dependent on the presence of Stat3. Hepcidin-mediated transcriptional changes modulated LPS-induced transcription in both cultured macrophages and in vivo mouse models, as demonstrated by suppression of IL-6 and TNF-alpha transcript and secreted protein. Hepcidin-mediated transcription in mice also suppressed toxicity and morbidity due to single doses of LPS, poly(I:C), and turpentine, which is used to model chronic inflammatory disease. Most notably, we demonstrated that hepcidin pretreatment protected mice from a lethal dose of LPS and that hepcidin-knockout mice could be rescued from LPS toxicity by injection of hepcidin. The results of our study suggest a new function for hepcidin in modulating acute inflammatory responses.

  5. MicroRNA-146a modulates human bronchial epithelial cell survival in response to the cytokine-induced apoptosis

    International Nuclear Information System (INIS)

    Liu Xiangde; Nelson, Amy; Wang Xingqi; Kanaji, Nobuhiro; Kim, Miok; Sato, Tadashi; Nakanishi, Masanori; Li Yingji; Sun Jianhong; Michalski, Joel; Patil, Amol; Basma, Hesham; Rennard, Stephen I.

    2009-01-01

    MicroRNA plays an important role in cell differentiation, proliferation and cell death. The current study found that miRNA-146a was up-regulated in human bronchial epithelial cells (HBECs) in response to stimulation by TGF-ss1 plus cytomix (a mixture of IL-1ss, IFN-γ and TNF-α). TGF-ss1 plus cytomix (TCM) induced apoptosis in HBECs (3.4 ± 0.6% of control vs 83.1 ± 4.0% of TCM treated cells, p < 0.01), and this was significantly blocked by the miRNA-146a mimic (8.8 ± 1.5%, p < 0.01). In contrast, a miRNA-146a inhibitor had only a modest effect on cell survival but appeared to augment the induction of epithelial-mesenchymal transition (EMT) in response to the cytokines. The MicroRNA-146a mimic appears to modulate HBEC survival through a mechanism of up-regulating Bcl-XL and STAT3 phosphorylation, and by this mechanism it could contribute to tissue repair and remodeling.

  6. Canonical and Non-Canonical Aspects of JAK-STAT Signaling: Lessons from Interferons for Cytokine Responses.

    Science.gov (United States)

    Majoros, Andrea; Platanitis, Ekaterini; Kernbauer-Hölzl, Elisabeth; Rosebrock, Felix; Müller, Mathias; Decker, Thomas

    2017-01-01

    Janus kinase (JAK)-signal transducer and activator of transcription (STAT) signal transduction mediates cytokine responses. Canonical signaling is based on STAT tyrosine phosphorylation by activated JAKs. Downstream of interferon (IFN) receptors, activated JAKs cause the formation of the transcription factors IFN-stimulated gene factor 3 (ISGF3), a heterotrimer of STAT1, STAT2 and interferon regulatory factor 9 (IRF9) subunits, and gamma interferon-activated factor (GAF), a STAT1 homodimer. In recent years, several deviations from this paradigm were reported. These include kinase-independent JAK functions as well as extra- and intranuclear activities of U-STATs without phosphotyrosines. Additionally, transcriptional control by STAT complexes resembling neither GAF nor ISGF3 contributes to transcriptome changes in IFN-treated cells. Our review summarizes the contribution of non-canonical JAK-STAT signaling to the innate antimicrobial immunity imparted by IFN. Moreover, we touch upon functions of IFN pathway proteins beyond the IFN response. These include metabolic functions of IRF9 as well as the regulation of natural killer cell activity by kinase-dead TYK2 and different phosphorylation isoforms of STAT1.

  7. Canonical and Non-Canonical Aspects of JAK–STAT Signaling: Lessons from Interferons for Cytokine Responses

    Science.gov (United States)

    Majoros, Andrea; Platanitis, Ekaterini; Kernbauer-Hölzl, Elisabeth; Rosebrock, Felix; Müller, Mathias; Decker, Thomas

    2017-01-01

    Janus kinase (JAK)–signal transducer and activator of transcription (STAT) signal transduction mediates cytokine responses. Canonical signaling is based on STAT tyrosine phosphorylation by activated JAKs. Downstream of interferon (IFN) receptors, activated JAKs cause the formation of the transcription factors IFN-stimulated gene factor 3 (ISGF3), a heterotrimer of STAT1, STAT2 and interferon regulatory factor 9 (IRF9) subunits, and gamma interferon-activated factor (GAF), a STAT1 homodimer. In recent years, several deviations from this paradigm were reported. These include kinase-independent JAK functions as well as extra- and intranuclear activities of U-STATs without phosphotyrosines. Additionally, transcriptional control by STAT complexes resembling neither GAF nor ISGF3 contributes to transcriptome changes in IFN-treated cells. Our review summarizes the contribution of non-canonical JAK–STAT signaling to the innate antimicrobial immunity imparted by IFN. Moreover, we touch upon functions of IFN pathway proteins beyond the IFN response. These include metabolic functions of IRF9 as well as the regulation of natural killer cell activity by kinase-dead TYK2 and different phosphorylation isoforms of STAT1. PMID:28184222

  8. Cytokine responses to novel antigens in a peri-urban population in Brazil exposed to Leishmania infantum chagasi.

    Science.gov (United States)

    Stober, Carmel B; Jeronimo, Selma M B; Pontes, Nubia N; Miller, E Nancy; Blackwell, Jenefer M

    2012-10-01

    Visceral leishmaniasis (VL) is fatal if untreated, and there are no vaccines for this disease. High levels of CD4-derived interferon-γ (IFN-γ) in the presence of low levels of interleukin-10 (IL-10) predicts vaccine success. Tumor necrosis factor-α (TNF-α) is also important in this process. We characterized human immune responses in three groups exposed to Leishmania infantum chagasi in Brazil: 1) drug-cured VL patients (recovered VL); 2) asymptomatic persons with positive Leishmania-specific delayed-type hypersensitivity skin reactions (DTH+); and 3) DTH-negative household contacts. Magnitude of DTH correlated with crude Leishmania antigen-driven IFN-γ, TNF-α, and IL-5, but not IL-10. DTH+ persons showed equivalent levels of IFN-γ, but higher levels of IL-10, to tryparedoxin peroxidase and Leishmania homolog of receptor for activated C kinase compared with recovered VL patients. The IFN-γ:IL-10 and TNF-α:IL-10 ratios were higher in recovered VL patients than in DTH+ persons. Seven of 11 novel candidates (R71, L37, N52, L302.06, M18, J41, and M22) elicited cytokine responses (36-71% of responders) in recovered VL patients and DTH+ persons. This result confirmed their putative status as cross-species vaccine/immunotherapeutic candidates.

  9. The Coda of the Transient Response in a Sensitive Cochlea: A Computational Modeling Study.

    Directory of Open Access Journals (Sweden)

    Yizeng Li

    2016-07-01

    Full Text Available In a sensitive cochlea, the basilar membrane response to transient excitation of any kind-normal acoustic or artificial intracochlear excitation-consists of not only a primary impulse but also a coda of delayed secondary responses with varying amplitudes but similar spectral content around the characteristic frequency of the measurement location. The coda, sometimes referred to as echoes or ringing, has been described as a form of local, short term memory which may influence the ability of the auditory system to detect gaps in an acoustic stimulus such as speech. Depending on the individual cochlea, the temporal gap between the primary impulse and the following coda ranges from once to thrice the group delay of the primary impulse (the group delay of the primary impulse is on the order of a few hundred microseconds. The coda is physiologically vulnerable, disappearing when the cochlea is compromised even slightly. The multicomponent sensitive response is not yet completely understood. We use a physiologically-based, mathematical model to investigate (i the generation of the primary impulse response and the dependence of the group delay on the various stimulation methods, (ii the effect of spatial perturbations in the properties of mechanically sensitive ion channels on the generation and separation of delayed secondary responses. The model suggests that the presence of the secondary responses depends on the wavenumber content of a perturbation and the activity level of the cochlea. In addition, the model shows that the varying temporal gaps between adjacent coda seen in experiments depend on the individual profiles of perturbations. Implications for non-invasive cochlear diagnosis are also discussed.

  10. A novel immune-to-CNS communication pathway: cells of the meninges surrounding the spinal cord CSF space produce proinflammatory cytokines in response to an inflammatory stimulus.

    Science.gov (United States)

    Wieseler-Frank, Julie; Jekich, Brian M; Mahoney, John H; Bland, Sondra T; Maier, Steven F; Watkins, Linda R

    2007-07-01

    Pain is enhanced in response to elevations of proinflammatory cytokines in spinal cerebrospinal fluid (CSF), following either intrathecal injection of these cytokines or intrathecal immune challenge with HIV-1 gp120 that induces cytokine release. Spinal cord glia have been assumed to be the source of endogenous proinflammatory cytokines that enhance pain. However, assuming that spinal cord glia are the sole source of CSF cytokines may be an underestimate, as the cellular composition of the meninges surrounding the spinal cord CSF space includes several cell types known to produce proinflammatory cytokines. The present experiments provide the first investigation of the immunocompetent nature of the spinal cord meninges. Here, we explore whether rat meninges are responsive to intrathecal gp120. These studies demonstrate that: (a) intrathecal gp120 upregulates meningeal gene expression of proinflammatory signals, including tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), interleukin 6 (IL-6), and inducible nitric oxide synthase (iNOS), and (b) intrathecal gp120 induces meningeal release of TNF-alpha, IL-1beta, and IL-6. In addition, stimulation of isolated meninges in vitro with gp120 induced the release of TNF-alpha and IL-1beta, indicating that the resident cells of the meninges are able to respond without immune cell recruitment. Taken together, these data document that the meninges are responsive to immunogenic stimuli in the CSF and that the meninges may be a source of immune products detected in CSF. The ability of the meninges to release to proinflammatory signals suggests a potential role in the modulation of pain.

  11. Effect of nutrient deficiencies on in vitro Th1 and Th2 cytokine response of peripheral blood mononuclear cells to Plasmodium falciparum infection

    NARCIS (Netherlands)

    Mbugi, E.V.; Meijerink, M.; Veenemans, J.; Jeurink, P.V.; McCall, M.; Olomi, R.M.; Shao, J.F.; Chilongola, J.; Verhoef, H.; Savelkoul, H.F.J.

    2010-01-01

    Background - An appropriate balance between pro-inflammatory and anti-inflammatory cytokines that mediate innate and adaptive immune responses is required for effective protection against human malaria and to avoid immunopathology. In malaria endemic countries, this immunological balance may be

  12. Heterogeneity in both cytokine production and responsiveness of a panel of monoclonal human Epstein-Barr virus-transformed B-cell lines

    NARCIS (Netherlands)

    Jochems, G. J.; Klein, M. R.; Jordens, R.; Pascual-Salcedo, D.; van Boxtel-Oosterhof, F.; van Lier, R. A.; Zeijlemaker, W. P.

    1991-01-01

    To optimize growth and Ig production of in vitro-cultured Epstein-Barr virus (EBV)-transformed B cells, a panel of six monoclonal EBV B-cell lines was analyzed for autocrine growth factor production and responsiveness to various cytokines. Three cell lines produced Il-I and four produced Il-6,

  13. Cytokine responses in primary chicken embryo intestinal cells infected with Campylobacter jejuni strains of human and chicken origin and the expression of bacterial virulence-associated genes

    DEFF Research Database (Denmark)

    Li, Yiping; Ingmer, Hanne; Madsen, Mogens

    2008-01-01

    Background Campylobacter jejuni is a major cause of inflammatory diarrhoea in humans and is considered a commensal of the gastroenteric tract of the avian host. However, little is known about the interaction between C. jejuni and the avian host including the cytokine responses and the expression...

  14. Frequency-dependent transient response of an oscillating electrically actuated droplet

    International Nuclear Information System (INIS)

    Dash, S; Kumari, N; Garimella, S V

    2012-01-01

    The transient response of a millimeter-sized sessile droplet under electrical actuation is experimentally investigated. Under dc actuation, the droplet spreading rate increases as the applied voltage is increased due to the higher electrical forces induced. At sufficiently high dc voltages, competition between the electrical actuation force, droplet inertia, the retarding surface tension force and contact line friction leads to droplet oscillation. The timescale for the droplet to attain its maximum wetted diameter during step actuation is analyzed. Systematic experiments are conducted over a frequency range of 5–200 Hz and actuation voltages of 40–80 V rms to determine the dependence of droplet oscillation on these parameters. The response of the droplet to different actuation frequencies and voltages is determined in terms of its contact angle and contact radius variation. The frequency of the driving force (equal to twice the frequency of the applied electrical signal) determines the mode of oscillation of the droplet which, together with its resonance characteristics, governs whether the droplet contact angle and contact radius vary in phase or out of phase with each other. In addition to the primary frequency response at the electrical forcing frequency, the droplet oscillation exhibits sub-harmonic oscillation at half of the forcing frequency that is attributed to the parametric nature of the electrical force acting on the triple contact line of the droplet. (paper)

  15. Predicting decadal trends and transient responses of radiocarbon storage and fluxes in a temperate forest soil

    Directory of Open Access Journals (Sweden)

    C. A. Sierra

    2012-08-01

    Full Text Available Representing the response of soil carbon dynamics to global environmental change requires the incorporation of multiple tools in the development of predictive models. An important tool to construct and test models is the incorporation of bomb radiocarbon in soil organic matter during the past decades. In this manuscript, we combined radiocarbon data and a previously developed empirical model to explore decade-scale soil carbon dynamics in a temperate forest ecosystem at the Harvard Forest, Massachusetts, USA. We evaluated the contribution of different soil C fractions to both total soil CO2 efflux and microbially respired C. We tested the performance of the model based on measurable soil organic matter fractions against a decade of radiocarbon measurements. The model was then challenged with radiocarbon measurements from a warming and N addition experiment to test multiple hypotheses about the different response of soil C fractions to the experimental manipulations. Our results showed that the empirical model satisfactorily predicts the trends of radiocarbon in litter, density fractions, and respired CO2 observed over a decade in the soils not subjected to manipulation. However, the model, modified with prescribed relationships for temperature and decomposition rates, predicted most but not all the observations from the field experiment where soil temperatures and nitrogen levels were increased, suggesting that a larger degree of complexity and mechanistic relations need to be added to the model to predict short-term responses and transient dynamics.

  16. IRAK-M expression limits dendritic cell activation and proinflammatory cytokine production in response to Helicobacter pylori.

    Directory of Open Access Journals (Sweden)

    Jessica Shiu

    Full Text Available Helicobacter pylori (H. pylori infects the gastric mucosa and persists for the life of the host. Bacterial persistence may be due to the induction of regulatory T cells (Tregs whichmay have protective effects against other diseases such as asthma. It has been shown that H. pylori modulates the T cell response through dendritic cell reprogramming but the molecular pathways involved are relatively unknown. The goal of this study was to identify critical elements of dendritic cell (DC activation and evaluate potential influence on immune activation. Microarray analysis was used to demonstrate limited gene expression changes in H. pylori stimulated bone marrow derived DCs (BMDCs compared to the BMDCs stimulated with E. coli. IRAK-M, a negative regulator of TLR signaling, was upregulated and we selectedit for investigation of its role in modulating the DC and T cell responses. IRAK-M(-/- and wild type BMDC were compared for their response to H. pylori. Cells lacking IRAK-M produced significantly greater amounts of proinflammatory MIP-2 and reduced amounts of immunomodulatory IL-10 than wild type BMDC. IRAK-M(-/- cells also demonstrated increased MHC II expression upon activation. However, IRAK-M(-/- BMDCs were comparable to wild type BMDCs in inducing T-helper 17 (TH17 and Treg responses as demonstrated in vitro using BMDC CD4+ T cells co-culture assays,and in vivo though the adoptive transfer of CD4(+ FoxP3-GFP T cells into H. pylori infected IRAK-M(-/- mice. These results suggest that H. pylori infection leads to the upregulation of anti-inflammatory molecules like IRAK-M and that IRAK-M has a direct impact on innate functions in DCs such as cytokine and costimulation molecule upregulation but may not affect T cell skewing.

  17. Erythropoietin augments the cytokine response to acute endotoxin-induced inflammation in humans

    DEFF Research Database (Denmark)

    Hojman, Pernille; Taudorf, Sarah; Lundby, Carsten

    2009-01-01

    in a human in vivo model of acute systemic low-grade inflammation, we measured circulating inflammatory mediators after intravenous administration of Escherichia coli endotoxin (LPS) bolus injection (0.1 ng/kg of body weight) in young healthy male subjects. The subjects were divided into three groups...... receiving either (1) LPS alone, (2) EPO alone (15,000 IE of rHuEPO) or (3) EPO and LPS. Endotoxin administration alone induced a 3-, 12- and 5-fold increase in plasma concentrations of TNF-alpha, IL-6 and IL-10, respectively, 3h after LPS challenge. When EPO was given prior to a bolus injection...... with endotoxin, the levels of TNF-alpha and IL-6 were enhanced by 5- and 40-fold, respectively, whereas the endotoxin-induced increase in IL-10 response was not influenced by EPO. In contrast to our hypothesis, we find that EPO augments the acute inflammatory effect....

  18. Transient Response Improvement of Microgrids Exploiting the Inertia of a Doubly-Fed Induction Generator (DFIG

    Directory of Open Access Journals (Sweden)

    Christina N. Papadimitriou

    2010-06-01

    Full Text Available Storage devices are introduced in microgrids in order to secure their power quality, power regularity and offer ancillary services in a transient period. In the transition period of a low voltage microgrid, from the connected mode of operation to the islanded mode of operation, the power unbalance can be partly covered by the inertia energy of the existing power sources. This paper proposes fuzzy local controllers exploiting the inertia of a Wind Turbine (WT with a Doubly Fed Induction Generator (DFIG, if such a machine exists in the microgrid, in order to decrease the necessary storage devices and the drawbacks that arise. The proposed controllers are based in fuzzy logic due to the non linear and stochastic behavior of the system. Two cases are studied and compared during the transient period where the microgrid architecture and the DFIG controller differ. In the first case, the understudy microgrid includes a hybrid fuel cell system (FCS-battery system and a WT with a DFIGURE. The DFIG local controller in this case is also based in fuzzy logic and follows the classical optimum power absorption scenario for the WT. The transition of the microgrid from the connected mode of operation to the islanded mode is evaluated and, especially, the battery contribution is estimated. In the second case, the battery is eliminated. The fuzzy controller of the DFIG during the transition provides primary frequency control and local bus voltage support exploiting the WT inertia. The response of the system is estimated in both cases using MATLAB/Simulink software package.

  19. Cytokine responses to the anti-schistosome vaccine candidate antigen glutathione-S-transferase vary with host age and are boosted by praziquantel treatment.

    Directory of Open Access Journals (Sweden)

    Claire D Bourke

    2014-05-01

    Full Text Available Improved helminth control is required to alleviate the global burden of schistosomiasis and schistosome-associated pathologies. Current control efforts rely on the anti-helminthic drug praziquantel (PZQ, which enhances immune responses to crude schistosome antigens but does not prevent re-infection. An anti-schistosome vaccine based on Schistosoma haematobium glutathione-S-transferase (GST is currently in Phase III clinical trials, but little is known about the immune responses directed against this antigen in humans naturally exposed to schistosomes or how these responses change following PZQ treatment.Blood samples from inhabitants of a Schistosoma haematobium-endemic area were incubated for 48 hours with or without GST before (n = 195 and six weeks after PZQ treatment (n = 107. Concentrations of cytokines associated with innate inflammatory (TNFα, IL-6, IL-8, type 1 (Th1; IFNγ, IL-2, IL-12p70, type 2 (IL-4, IL-5, IL-13, type 17 (IL-17A, IL-21, IL-23p19 and regulatory (IL-10 responses were quantified in culture supernatants via enzyme-linked immunosorbent assay (ELISA. Factor analysis and multidimensional scaling were used to analyse multiple cytokines simultaneously.A combination of GST-specific type 2 (IL-5 and IL-13 and regulatory (IL-10 cytokines was significantly lower in 10-12 year olds, the age group at which S. haematobium infection intensity and prevalence peak, than in 4-9 or 13+ year olds. Following PZQ treatment there was an increase in the number of participants producing detectable levels of GST-specific cytokines (TNFα, IL-6, IL-8, IFNγ, IL-12p70, IL-13 and IL-23p19 and also a shift in the GST-specific cytokine response towards a more pro-inflammatory phenotype than that observed before treatment. Participant age and pre-treatment infection status significantly influenced post-treatment cytokine profiles.In areas where schistosomiasis is endemic host age, schistosome infection status and PZQ treatment affect the

  20. Shock-induced thermal wave propagation and response analysis of a viscoelastic thin plate under transient heating loads

    Science.gov (United States)

    Li, Chenlin; Guo, Huili; Tian, Xiaogeng

    2018-04-01

    This paper is devoted to the thermal shock analysis for viscoelastic materials under transient heating loads. The governing coupled equations with time-delay parameter and nonlocal scale parameter are derived based on the generalized thermo-viscoelasticity theory. The problem of a thin plate composed of viscoelastic material, subjected to a sudden temperature rise at the boundary plane, is solved by employing Laplace transformation techniques. The transient responses, i.e. temperature, displacement, stresses, heat flux as well as strain, are obtained and discussed. The effects of time-delay and nonlocal scale parameter on the transient responses are analyzed and discussed. It can be observed that: the propagation of thermal wave is dynamically smoothed and changed with the variation of time-delay; while the displacement, strain, and stress can be rapidly reduced by nonlocal scale parameter, which can be viewed as an important indicator for predicting the stiffness softening behavior for viscoelastic materials.

  1. Cytokine Response to Diet and Exercise Affects Atheromatous Matrix Metalloproteinase-2/9 Activity in Mice.

    Science.gov (United States)

    Shon, Soo-Min; Jang, Hee Jeong; Schellingerhout, Dawid; Kim, Jeong-Yeon; Ryu, Wi-Sun; Lee, Su-Kyoung; Kim, Jiwon; Park, Jin-Yong; Oh, Ji Hye; Kang, Jeong Wook; Je, Kang-Hoon; Park, Jung E; Kim, Kwangmeyung; Kwon, Ick Chan; Lee, Juneyoung; Nahrendorf, Matthias; Park, Jong-Ho; Kim, Dong-Eog

    2017-09-25

    The aim of this study is to identify the principal circulating factors that modulate atheromatous matrix metalloproteinase (MMP) activity in response to diet and exercise.Methods and Results:Apolipoprotein-E knock-out (ApoE -/- ) mice (n=56) with pre-existing plaque, fed either a Western diet (WD) or normal diet (ND), underwent either 10 weeks of treadmill exercise or had no treatment. Atheromatous MMP activity was visualized using molecular imaging with a MMP-2/9 activatable near-infrared fluorescent (NIRF) probe. Exercise did not significantly reduce body weight, visceral fat, and plaque size in either WD-fed animals or ND-fed animals. However, atheromatous MMP-activity was different; ND animals that did or did not exercise had similarly low MMP activities, WD animals that did not exercise had high MMP activity, and WD animals that did exercise had reduced levels of MMP activity, close to the levels of ND animals. Factor analysis and path analysis showed that soluble vascular cell adhesion molecule (sVCAM)-1 was directly positively correlated to atheromatous MMP activity. Adiponectin was indirectly negatively related to atheromatous MMP activity by way of sVCAM-1. Resistin was indirectly positively related to atheromatous MMP activity by way of sVCAM-1. Visceral fat amount was indirectly positively associated with atheromatous MMP activity, by way of adiponectin reduction and resistin elevation. MMP-2/9 imaging of additional mice (n=18) supported the diet/exercise-related anti-atherosclerotic roles for sVCAM-1. Diet and exercise affect atheromatous MMP activity by modulating the systemic inflammatory milieu, with sVCAM-1, resistin, and adiponectin closely interacting with each other and with visceral fat.

  2. Transient expression of protein tyrosine phosphatases encoded in Cotesia plutellae bracovirus inhibits insect cellular immune responses

    Science.gov (United States)

    Ibrahim, Ahmed M. A.; Kim, Yonggyun

    2008-01-01

    Several immunosuppressive factors are associated with parasitism of an endoparasitoid wasp, Cotesia plutellae, on the diamondback moth, Plutella xylostella. C. plutellae bracovirus (CpBV) encodes a large number of putative protein tyrosine phosphatases (PTPs), which may play a role in inhibiting host cellular immunity. To address this inhibitory hypothesis of CpBV-PTPs, we performed transient expression of individual CpBV-PTPs in hemocytes of the beet armyworm, Spodoptera exigua, and analyzed their cellular immune responses. Two different forms of CpBV-PTPs were chosen and cloned into a eukaryotic expression vector under the control of the p10 promoter of baculovirus: one with the normal cysteine active site (CpBV-PTP1) and the other with a mutated active site (CpBV-PTP5). The hemocytes transfected with CpBV-PTP1 significantly increased in PTP activity compared to control hemocytes, but those with CpBV-PTP5 exhibited a significant decrease in the PTP activity. All transfected hemocytes exhibited a significant reduction in both cell spreading and encapsulation activities compared to control hemocytes. Co-transfection of CpBV-PTP1 together with its double-stranded RNA reduced the messenger RNA (mRNA) level of CpBV-PTP1 and resulted in recovery of both hemocyte behaviors. This is the first report demonstrating that the polydnaviral PTPs can manipulate PTP activity of the hemocytes to interrupt cellular immune responses.

  3. Dynamical Networks Characterization of Geomagnetic Substorms and Transient Response to the Solar Wind State.

    Science.gov (United States)

    Chapman, S. C.; Dods, J.; Gjerloev, J. W.

    2017-12-01

    Observations of how the solar wind interacts with earth's magnetosphere, and its dynamical response, are increasingly becoming a data analytics challenge. Constellations of satellites observe the solar corona, the upstream solar wind and throughout earth's magnetosphere. These data are multipoint in space and extended in time, so in principle are ideal for study using dynamical networks to characterize the full time evolving spatial pattern. We focus here on analysis of data from the full set of 100+ auroral ground based magnetometer stations that have been collated by SuperMAG. Spatio-temporal patterns of correlation between the magnetometer time series can be used to form a dynamical network [1]. The properties of the network can then be captured by (time dependent) network parameters. This offers the possibility of characterizing detailed spatio-temporal pattern by a few parameters, so that many events can then be compared [2] with each other. Whilst networks are in widespread use in the data analytics of societal and commercial data, there are additional challenges in their application to physical timeseries. Determining whether two nodes (here, ground based magnetometer stations) are connected in a network (seeing the same dynamics) requires normalization w.r.t. the detailed sensitivities and dynamical responses of specific observing stations and seasonal conductivity variations and we have developed methods to achieve this dynamical normalization. The detailed properties of the network capture time dependent spatial correlation in the magnetometer responses and we will show how this can be used to infer a transient current system response to magnetospheric activity. [l] Dods et al, J. Geophys. Res 120, doi:10.1002/2015JA02 (2015). [2] Dods et al, J. Geophys. Res. 122, doi:10.1002/2016JA02 (2017).

  4. Human bladder uroepithelial cells synergize with monocytes to promote IL-10 synthesis and other cytokine responses to uropathogenic Escherichia coli.

    Directory of Open Access Journals (Sweden)

    Benjamin L Duell

    Full Text Available Urinary tract infections are a major source of morbidity for women and the elderly, with Uropathogenic Escherichia coli (UPEC being the most prevalent causative pathogen. Studies in recent years have defined a key anti-inflammatory role for Interleukin-10 (IL-10 in urinary tract infection mediated by UPEC and other uropathogens. We investigated the nature of the IL-10-producing interactions between UPEC and host cells by utilising a novel co-culture model that incorporated lymphocytes, mononuclear and uroepithelial cells in histotypic proportions. This co-culture model demonstrated synergistic IL-10 production effects between monocytes and uroepithelial cells following infection with UPEC. Membrane inserts were used to separate the monocyte and uroepithelial cell types during infection and revealed two synergistic IL-10 production effects based on contact-dependent and soluble interactions. Analysis of a comprehensive set of immunologically relevant biomarkers in monocyte-uroepithelial cell co-cultures highlighted that multiple cytokine, chemokine and signalling factors were also produced in a synergistic or antagonistic fashion. These results demonstrate that IL-10 responses to UPEC occur via multiple interactions between several cells types, implying a complex role for infection-related IL-10 during UTI. Development and application of the co-culture model described in this study is thus useful to define the degree of contact dependency of biomarker production to UPEC, and highlights the relevance of histotypic co-cultures in studying complex host-pathogen interactions.

  5. Synergistic immune responses induced by endogenous retrovirus and herpesvirus antigens result in increased production of inflammatory cytokines in multiple sclerosis patients

    DEFF Research Database (Denmark)

    Brudek, T; Christensen, T; Hansen, H J

    2008-01-01

    Human endogenous retroviruses (HERV) and herpesviruses are increasingly associated with the pathogenesis of the neurological inflammatory disease multiple sclerosis (MS). Herpesviruses are capable of HERV activation and simultaneous presence of HERV and herpesvirus antigens have a synergistic...... effect on cell-mediated immune responses, which tend to be higher in MS patients in comparison with healthy individuals. Here, we investigate whether these synergistic immune responses are reflected in changes in the production of proinflammatory cytokines. Using enzyme-linked immunosorbent assays...

  6. Dynamic Response in Transient Stress-Field Behavior Induced by Hydraulic Fracturing

    Science.gov (United States)

    Jenkins, Andrew

    Hydraulic fracturing is a technique which is used to exploit geologic features and subsurface properties in an effort to increase production in low-permeability formations. The process of hydraulic fracturing provides a greater surface contact area between the producing formation and the wellbore and thus increases the amount of recoverable hydrocarbons from within the reservoir. The use of this stimulation technique has brought on massive applause from the industry due to its widespread success and effectiveness, however the dynamic processes that take part in the development of hydraulic fractures is a relatively new area of research with respect to the massive scale operations that are seen today. The process of hydraulic fracturing relies upon understanding and exploiting the in-situ stress distribution throughout the area of study. These in-situ stress conditions are responsible for directing fracture orientation and propagation paths throughout the period of injection. The relative magnitude of these principle stresses is key in developing a successful stimulation plan. In horizontal well plan development the interpretation of stress within the reservoir is required for determining the azimuth of the horizontal well path. These horizontal laterals are typically oriented in a manner such that the well path lies parallel to the minimum horizontal stress. This allows for vertical fractures to develop transversely to the wellbore, or normal to the least principle stress without the theoretical possibility of fractures overlapping, creating the most efficient use of the fluid energy during injection. The orientation and magnitude of these in-situ stress fields however can be dynamic, controlled by the subsequent fracture propagation and redistribution of the surrounding stresses. That is, that as the fracture propagates throughout the reservoir, the relative stress fields surrounding the fractures may see a shift and deviate from their original direction or

  7. Real-Time Gas Identification by Analyzing the Transient Response of Capillary-Attached Conductive Gas Sensor

    Directory of Open Access Journals (Sweden)

    Behzad Bahraminejad

    2010-05-01

    Full Text Available In this study, the ability of the Capillary-attached conductive gas sensor (CGS in real-time gas identification was investigated. The structure of the prototype fabricated CGS is presented. Portions were selected from the beginning of the CGS transient response including the first 11 samples to the first 100 samples. Different feature extraction and classification methods were applied on the selected portions. Validation of methods was evaluated to study the ability of an early portion of the CGS transient response in target gas (TG identification. Experimental results proved that applying extracted features from an early part of the CGS transient response along with a classifier can distinguish short-chain alcohols from each other perfectly. Decreasing time of exposition in the interaction between target gas and sensing element improved the reliability of the sensor. Classification rate was also improved and time of identification was decreased. Moreover, the results indicated the optimum interval of the early transient response of the CGS for selecting portions to achieve the best classification rates.

  8. Nonlinear transient responses of beams and rings to impulse loading or fragment impact

    International Nuclear Information System (INIS)

    Witmer, E.A.; Stagliano, T.R.; Rodal, J.J.A.

    1977-01-01

    The present paper is concerned with a very limited part of the cited fragment threat; namely, fragments from high speed rotating machinery such as (1) aircraft engine rotors and (2) stationary power plant turbine rotors. Further, it is assumed that the structures intended to contain or control these fragments consist of initially-isotropic elastic-plastic metals. Certain potential containment/control (C/C) structures behave in a planar (or two-dimensional) fashion while other fragment-attacked C/C structures will undergo general three-dimensional deformations. Predictions for only the former category of fragment-attacked structures are discussed in the present paper. Pertinent experimental data discussed here on fragment-attacked structures include (a) steel-sphere impact data involving beam targets and (b) engine rotor fragment impact against a steel containment ring. In all of these cases large-deflection, elastic-plastic transient structural response occur. The governing equations employed are presented in the present analysis to predict the responses of protective (metal) structures to engine-rotor-fragment impact. The protective structure is intended either to contain or to deflect the attacking fragments away from important regions; large-deflection, elasic-plastic structural response is expected because these protective structures must have the least feasible weight. Concise geometric and assumed-displacement-field descriptions of the several types of finite elements to be utilized in subsequent examples are given, together with several categories of strain displacement relations. Both low- and higher-order elements are discussed

  9. Understanding the Slow Transient Optoelectronic Response of Hybrid Organic-Inorganic Halide Perovskites

    Science.gov (United States)

    Jacobs, Daniel Louis

    Hybrid organic-inorganic halide perovskites, particularly methylammonium lead triiodide (MAPbI3), have emerged within the past decade as an exciting class of photovoltaic materials. In less than ten years, MAPbI3-based photovoltaic devices have seen unprecedented performance growth, with photoconversion efficiency increasing from 3% to over 22%, making it competitive with traditional high-efficiency solar cells. Furthermore, the fabrication of MAPbI3 devices utilize low-temperature solution processing, which could facilitate ultra low cost manufacturing. However, MAPbI3 suffers from significant instabilities under working conditions that have limited their applications outside of the laboratory. The instability of the MAPbI3 material can be generalized as a complex, slow transient optoelectronic response (STOR). The mechanism of the generalized STOR is dependent on the native defects of MAPbI3, but detailed understanding of the material defect properties is complicated by the complex ionic bonding of MAPbI3. Furthermore, characterization of the intrinsic material's response is complicated by the diverse approach to material processing and device architecture across laboratories around the world. In order to understand and mitigate the significant problems of MAPbI3 devices, a new approach focused on the material response, rather than the full device response, must be pursued. This dissertation highlights the work to analyze and mitigate the STOR intrinsic to MAPbI3. An experimental platform was developed based on lateral interdigitated electrode (IDE) arrays capable of monitoring the current and photoluminescence response simultaneously. By correlating the dynamics of the current and photoluminescence (PL) responses, both charge trapping and ion migration mechanisms were identified to contribute to the STOR. Next, a novel fabrication technique is introduced that is capable of reliably depositing MAPbI3 thin films with grain sizes at least an order of magnitude

  10. Probabilistic estimates of 1.5-degree carbon budgets based on uncertainty in transient climate response and aerosol forcing

    Science.gov (United States)

    Partanen, A. I.; Mengis, N.; Jalbert, J.; Matthews, D.

    2017-12-01

    Nations agreed to limit the increase in global mean surface temperature relative to the preindustrial era below 2 degrees Celsius and pursue efforts to a more ambitious goal of 1.5 degrees Celsius. To achieve these goals, it is necessary to assess the amount of cumulative carbon emissions compatible with these temperature targets, i.e. so called carbon budgets. In this work, we use the intermediate complexity University of Victoria Earth System Climate Model (UVic ESCM) to assess how uncertainty in aerosol forcing and transient climate response transfers to uncertainty in future carbon budgets for burning fossil fuels. We create a perturbed parameter ensemble of model simulations by scaling aerosol forcing and transient climate response, and assess the likelihood of each simulation by comparing the simulated historical cumulative carbon emissions, CO2 concentration and radiative balance to observations. By weighting the results of each simulation with the likelihood of the simulation, the preliminary results give a carbon budget of 48 Pg C to reach 1.5 degree Celsius temperature increase. The small weighted mean is due to large fraction of simulations with strong aerosol forcing and transient climate response giving negative carbon budgets for this time period. The probability of the carbon budget being over 100 Pg C was 38% and 23% for over 200 Pg carbon budget. The carbon budgets after temperature stabilization at 1.5 degrees are even smaller with a weighted mean of -100 Pg C until the year 2200. The main reason for the negative carbon budgets after temperature stabilization is an assumed strong decrease in aerosol forcing in the 21st century. Conversely, simulations with weak aerosol forcing and transient climate response give positive carbon budgets. Our results highlight both the importance of reducing uncertainty in aerosol forcing and transient climate response, and of taking the non-CO2 forcers into account when estimating carbon budgets.

  11. Processes governing transient responses of the deep ocean buoyancy budget to a doubling of CO2

    Science.gov (United States)

    Palter, J. B.; Griffies, S. M.; Hunter Samuels, B. L.; Galbraith, E. D.; Gnanadesikan, A.

    2012-12-01

    Recent observational analyses suggest there is a temporal trend and high-frequency variability in deep ocean buoyancy in the last twenty years, a phenomenon reproduced even in low-mixing models. Here we use an earth system model (GFDL's ESM2M) to evaluate physical processes that influence buoyancy (and thus steric sea level) budget of the deep ocean in quasi-steady state and under a doubling of CO2. A new suite of model diagnostics allows us to quantitatively assess every process that influences the buoyancy budget and its temporal evolution, revealing surprising dynamics governing both the equilibrium budget and its transient response to climate change. The results suggest that the temporal evolution of the deep ocean contribution to sea level rise is due to a diversity of processes at high latitudes, whose net effect is then advected in the Eulerian mean flow to mid and low latitudes. In the Southern Ocean, a slowdown in convection and spin up of the residual mean advection are approximately equal players in the deep steric sea level rise. In the North Atlantic, the region of greatest deep steric sea level variability in our simulations, a decrease in mixing of cold, dense waters from the marginal seas and a reduction in open ocean convection causes an accumulation of buoyancy in the deep subpolar gyre, which is then advected equatorward.

  12. Low latitude ionospheric TEC responses to dynamical complexity quantifiers during transient events over Nigeria

    Science.gov (United States)

    Ogunsua, Babalola

    2018-04-01

    In this study, the values of chaoticity and dynamical complexity parameters for some selected storm periods in the year 2011 and 2012 have been computed. This was done using detrended TEC data sets measured from Birnin-Kebbi, Torro and Enugu global positioning system (GPS) receiver stations in Nigeria. It was observed that the significance of difference (SD) values were mostly greater than 1.96 but surprisingly lower than 1.96 in September 29, 2011. The values of the computed SD were also found to be reduced in most cases just after the geomagnetic storm with immediate recovery a day after the main phase of the storm while the values of Lyapunov exponent and Tsallis entropy remains reduced due to the influence of geomagnetic storms. It was also observed that the value of Lyapunov exponent and Tsallis entropy reveals similar variation pattern during storm period in most cases. Also recorded surprisingly were lower values of these dynamical quantifiers during the solar flare event of August 8th and 9th of the year 2011. The possible mechanisms responsible for these observations were further discussed in this work. However, our observations show that the ionospheric effects of some other possible transient events other than geomagnetic storms can also be revealed by the variation of chaoticity and dynamical complexity.

  13. Low temperature transient response and electroluminescence characteristics of OLEDs based on Alq3

    Science.gov (United States)

    Yuan, Chao; Guan, Min; Zhang, Yang; Li, Yiyang; Liu, Shuangjie; Zeng, Yiping

    2017-08-01

    In this work, the organic light-emitting diodes (OLEDs) based on Alq3 are fabricated. In order to make clear the transport mechanism of carriers in organic light-emitting devices at low temperature, detailed electroluminescence transient response and the current-voltage-luminescence (I-V-L) characteristics under different temperatures in those OLEDs are investigated. It founds that the acceleration of brightness increases with increasing temperature is maximum when the temperature is 200 K and it is mainly affected by the electron transport layer (Alq3). The MoO3 injection layer and the electroluminescent layer have great influence on the delay time when the temperature is 200 K. Once the temperature is greater than 250 K, the delay time is mainly affected by the MoO3 injection layer. On the contrary, the fall time is mainly affected by the electroluminescent material. The Vf is the average growth rate of fall time when the temperature increases 1 K which represents the accumulation rate of carriers. The difference between Vf caused by the MoO3 injection layer is 0.52 us/K and caused by the electroluminescent material Ir(ppy)3 is 0.73 us/K.

  14. Incorporating fan control into air-conditioning systems to improve energy efficiency and transient response

    International Nuclear Information System (INIS)

    Yeh, T.-J.; Chen, Yun-Jih; Hwang, Wei-Yang; Lin, Jin-Long

    2009-01-01

    Modern air-conditioners frequently incorporate variable-speed compressors and variable-opening expansion valves with feedback control to improve performance and power efficiency. Because making the fan speeds adjustable adds flexibility to the control design and thus can lead to further improvements in performance and efficiency, this paper proposes two control algorithms, respectively, incorporating the outdoor fan and the indoor fan as the additional control inputs for air-conditioning systems. Both of the control algorithms are designed based on a low-order, linear model obtained from system identification. The first algorithm, which modulates the outdoor fan speed, can reduce the steady state power consumption if the temperature difference between the condenser and the outdoor environment is controlled properly. The second algorithm, which adds one more degree of freedom to control by modulating the indoor fan speed, can improve the transient response because actuator saturations become less likely to occur. The two control algorithms are implemented on a split-type residential air-conditioner and their respective performance is validated experimentally.

  15. Inferring the Mode of Selection from the Transient Response to Demographic Perturbations

    Science.gov (United States)

    Balick, Daniel; Do, Ron; Reich, David; Sunyaev, Shamil

    2014-03-01

    Despite substantial recent progress in theoretical population genetics, most models work under the assumption of a constant population size. Deviations from fixed population sizes are ubiquitous in natural populations, many of which experience population bottlenecks and re-expansions. The non-equilibrium dynamics introduced by a large perturbation in population size are generally viewed as a confounding factor. In the present work, we take advantage of the transient response to a population bottleneck to infer features of the mode of selection and the distribution of selective effects. We develop an analytic framework and a corresponding statistical test that qualitatively differentiates between alleles under additive and those under recessive or more general epistatic selection. This statistic can be used to bound the joint distribution of selective effects and dominance effects in any diploid sexual organism. We apply this technique to human population genetic data, and severely restrict the space of allowed selective coefficients in humans. Additionally, one can test a set of functionally or medically relevant alleles for the primary mode of selection, or determine the local regional variation in dominance coefficients along the genome.

  16. Transient Dynamic Response of Delaminated Composite Rotating Shallow Shells Subjected to Impact

    Directory of Open Access Journals (Sweden)

    Amit Karmakar

    2006-01-01

    Full Text Available In this paper a transient dynamic finite element analysis is presented to study the response of delaminated composite pretwisted rotating shallow shells subjected to low velocity normal impact. Lagrange's equation of motion is used to derive the dynamic equilibrium equation and moderate rotational speeds are considered wherein the Coriolis effect is negligible. An eight noded isoparametric plate bending element is employed in the finite element formulation incorporating rotary inertia and effects of transverse shear deformation based on Mindlin's theory. To satisfy the compatibility of deformation and equilibrium of resultant forces and moments at the delamination crack front a multipoint constraint algorithm is incorporated which leads to unsymmetric stiffness matrices. The modified Hertzian contact law which accounts for permanent indentation is utilized to compute the contact force, and the time dependent equations are solved by Newmark's time integration algorithm. Parametric studies are performed in respect of location of delamination, angle of twist and rotational speed for centrally impacted graphite-epoxy composite cylindrical shells.

  17. Nonlinear transient responses of beams and rings to impulse loading or fragment impact

    International Nuclear Information System (INIS)

    Witmer, E.A.; Stagliano, T.R.; Rodal, J.J.A.

    1977-01-01

    Nuclear power plant protective structures may be subjected to various external missiles such as aircraft and tornado-generated missiles: telephone poles, planks, pipes, rods, automobiles, and other blown vehicles. Also, 'internally-generated missiles' such as fragments from powerplant rotors and aircraft engine rotors may impact protective structures. The present paper is concerned with a very limited part of the cited fragment threat; namely, fragments from high speed rotating machinery such as (1) aircraft engine rotors and (2) stationary power plant turbine rotors. Further, it is assumed that the structures intended to contain or control these fragments consist of initially-isotopic elastic-plastic metals. Certain potential containment/control (C/C) structures behave in a planar (or two-dimensional) fashion while other fragment-attacked C/C structures will undergo general three-dimensional deformations. Predictions for only the former category of fragment-attacked structures are discussed in the present paper. Pertinent experimental data discussed on fragment-attacked structures include (a) steel-sphere impact data involving beam targets and (b) engine rotor fragment impact against a steel containment ring. In all of these cases large-deflection, elastic-plastic transient structural responses occur. (Auth.)

  18. Response of GaAs charge storage devices to transient ionizing radiation

    Science.gov (United States)

    Hetherington, D. L.; Klem, J. F.; Hughes, R. C.; Weaver, H. T.

    Charge storage devices in which non-equilibrium depletion regions represent stored charge are sensitive to ionizing radiation. This results since the radiation generates electron-hole pairs that neutralize excess ionized dopant charge. Silicon structures, such as dynamic RAM or CCD cells are particularly sensitive to radiation since carrier diffusion lengths in this material are often much longer than the depletion width, allowing collection of significant quantities of charge from quasi-neutral sections of the device. For GaAs the situation is somewhat different in that minority carrier diffusion lengths are shorter than in silicon, and although mobilities are higher, we expect a reduction of radiation sensitivity as suggested by observations of reduced quantum efficiency in GaAs solar cells. Dynamic memory cells in GaAs have potential increased retention times. In this paper, we report the response of a novel GaAs dynamic memory element to transient ionizing radiation. The charge readout technique is nondestructive over a reasonable applied voltage range and is more sensitive to stored charge than a simple capacitor.

  19. Mechanical response of FFTF reference and P1 cladding tubes under transient heating

    International Nuclear Information System (INIS)

    Youngahl, C.A.; Ariman, T.; Lepacek, B.E.

    1977-01-01

    Burst tests of Type 316 stainless steel cladding tube samples subjected to increasing temperature and relatively constant internal pressure were conducted to assist in the pretest analysis of the P1 experiment performed in the Sodium Loop Safety Facility. This paper reports and analyzes the burst test results and those of subsequent transient heating work. The use of a modified extensometer in obtaining mechanical response data for stainless steel in the high temperature range is illustrated, some of such data is provided, and the potential of further experiments and analysis is indicated. Tubing of the same design as Fast Flux Test Facility (FFTF) cladding (20% cold worked, 0.230 in. OD, 15 mil wall) was tested as-received and after annealing or electrolytic thinning. P1 tubing (38% cold worked, 0.230 in. OD, 10 mil wall) was tested before and after aging under conditions anticipated in the P1 reactor experiment. The P1 cladding was designed to simulate FFTF tubing that had experienced irradiation embrittlement and attack by cesium oxide and sodium impurities

  20. Pharmacological analysis of calcium transients in response to gravity vector change in Arabidopsis hypocotyls and petioles.

    Science.gov (United States)

    Toyota, M.; Furuichi, T.; Tatsumi, H.; Sokabe, M.

    Plants regulate their growth and morphology in response to gravity field known as gravitropism in general In the process of gravitropism gravity sensing will form the critical earliest event which is supposed to take place in specialized cells statocytes such as columella cells and shoot endodermal cells Although gravistimulation is assumed to be converted into certain intracellular signals the underlying transduction mechanisms have hardly been explored One of the potential candidates for the intracellular signals is an increase in the cytoplasmic free calcium concentration Ca 2 c Here we measured Ca 2 c changes induced by gravistimulation in seedlings of Arabidopsis thaliana expressing aequorin as a calcium reporter When a plate of seedlings was turned through 180 r Ca 2 c transiently increased within 50 s and decayed exponentially with a time constant of ca 60 s The amplitude of the Ca 2 c increase was independent of the angular velocity of the rotation The Ca 2 c increase was reversibly blocked by extracellularly applied potential mechanosensitive channel blockers La 3 Gd 3 or a Ca 2 chelator BAPTA indicating that it arose from Ca 2 -influx via Ca 2 -permeable channel s on the plasma membrane Furthermore the Ca 2 c increase was attenuated by actin-disrupting drugs latrunculin B cytochalasin B but not by microtuble-disrupting drugs oryzalin nocodazole indicating that the activation of

  1. Effect of axial stress on the transient mechanical response of 20%, cold-worked Type 316 stainless-steel cladding

    International Nuclear Information System (INIS)

    Yamada, H.

    1979-01-01

    To understand the effects of the fuel-cladding mechanical interaction on the failure of 20% cold-worked Type 316 stainless-steel cladding during anticipated nuclear reactor transients, the transient mechanical response of the cladding was investigated using a transient tube burst method at a heating rate of 5.6 0 C/s and axial-to-hoop-stress ratios in the range of 1/2 to 2. The failure temperatures were observed to remain essentially constant for the transient tests at axial-to-hoop-stress ratios between 1/2 and 1, but to decrease with an increase in axial-to-hoop-stress ratios above unity. The uniform diametral strains to failure were observed to decrease monotonically with an increase in axial-to-hoop-stress ratio from 1/2 to 2, and in general, the uniform axial strains to failure were observed to increase with an increase in axial-to-hoop-stress ratio. The fracture of the cladding during thermal transients was found to be strongly affected by the maximum principal stress but not by the effective stress

  2. A Newly Emergent Turkey Arthritis Reovirus Shows Dominant Enteric Tropism and Induces Significantly Elevated Innate Antiviral and T Helper-1 Cytokine Responses.

    Directory of Open Access Journals (Sweden)

    Tamer A Sharafeldin

    Full Text Available Newly emergent turkey arthritis reoviruses (TARV were isolated from tendons of lame 15-week-old tom turkeys that occasionally had ruptured leg tendons. Experimentally, these TARVs induced remarkable tenosynovitis in gastrocnemius tendons of turkey poults. The current study aimed to characterize the location and the extent of virus replication as well as the cytokine response induced by TARV during the first two weeks of infection. One-week-old male turkeys were inoculated orally with TARV (O'Neil strain. Copy numbers of viral genes were estimated in intestines, internal organs and tendons at ½, 1, 2, 3, 4, 7, 14 days Post inoculation (dpi. Cytokine profile was measured in intestines, spleen and leg tendons at 0, 4, 7 and 14 dpi. Viral copy number peaked in jejunum, cecum and bursa of Fabricius at 4 dpi. Copy numbers increased dramatically in leg tendons at 7 and 14 dpi while minimal copies were detected in internal organs and blood during the same period. Virus was detected in cloacal swabs at 1-2 dpi, and peaked at 14 dpi indicating enterotropism of the virus and its early shedding in feces. Elevation of IFN-α and IFN-β was observed in intestines at 7 dpi as well as a prominent T helper-1 response (IFN-γ at 7 and 14 dpi. IFN-γ and IL-6 were elevated in gastrocnemius tendons at 14 dpi. Elevation of antiviral cytokines in intestines occurred at 7dpi when a significant decline of viral replication in intestines was observed. T helper-1 response in intestines and leg tendons was the dominant T-helper response. These results suggest the possible correlation between viral replication and cytokine response in early infection of TARV in turkeys. Our findings provide novel insights which help elucidate viral pathogenesis in turkey tendons infected with TARV.

  3. Experimental study for transient response of a double-tube thermosyphon (DTTH)

    International Nuclear Information System (INIS)

    Salem, M.A.M.

    2010-01-01

    study includes the analysis of:1-Boiling and non-boiling heat transfer coefficients of the eva porator.2-Temperature profile along the double-tube thermosyphon.In addition to the performance study for comparison purposes mainly involves:1-Transient response of the double-tube thermosyphon.2-Average evaporator heat transfer coefficient.3-Equivalent overall heat transfer coefficient.4-Effective thermal conductivity of thermosyphon.

  4. Clinical signs and hematologic, cytokine, and plasma nitric oxide alterations in response to Strongylus vulgaris infection in helminth-naïve ponies.

    Science.gov (United States)

    Hubert, Jeremy D; Seahorn, Thomas L; Klei, Thomas R; Hosgood, Giselle; Horohov, David W; Moore, Rustin M

    2004-07-01

    The objective of this study was to determine the effect of infection with Strongylus vulgaris on serum cytokines and plasma nitric oxide (NO) concentrations in helminth-naive ponies. Group 1 (n = 21) was given 500 S. vulgaris L3 larvae and group 2 (n = 7) received a saline control. Ponies were monitored daily for clinical signs, and blood was collected for complete blood cell counts and serum cytokines (TNF, IL-1, IL-6) quantification. Group 1 ponies were depressed, anorexic, and febrile for variable periods of time. Plasma NO was increased on day 21 in group 1 and on days 9 and 21 in group 2. Significant increases in total white blood cell counts, fibrinogen, and plasma protein concentrations in group 1 were found. Significant decreases in red blood cell counts and packed cell volume were also noted in group 1. There were no differences in serum cytokines across time in either group of ponies. Despite the lack of proinflammatory cytokine induction with the apparent inflammatory response to S. vulgaris there is evidence of a potential role of NO.

  5. Distinctive in vitro effects of T-cell growth cytokines on cytomegalovirus-stimulated T-cell responses of HIV-infected HAART recipients

    International Nuclear Information System (INIS)

    Patterson, Julie; Jesser, Renee; Weinberg, Adriana

    2008-01-01

    Functional immune reconstitution is limited after HAART, maintaining the interest in adjunctive immune-modulators. We compared in vitro the effects of the γ-chain T-cell growth cytokines IL-2, IL-4, IL-7 and IL-15 on cytomegalovirus-stimulated cell-mediated immunity. IL-2 and IL-15 increased cytomegalovirus-specific lymphocyte proliferation in HAART recipients, whereas IL-4 and IL-7 did not. The boosting effect of IL-2 and IL-15 on proliferation correlated with their ability to prevent late apoptosis. However, IL-2 increased the frequency of cells in early apoptosis, whereas IL-15 increased the frequency of fully viable cells. Both IL-2 and IL-15 increased cytomegalovirus-induced CD4 + and CD8 + T-cell proliferation and the synthesis of Th1 and pro-inflammatory cytokines and chemokines. However, only IL-2 increased the frequency of regulatory T cells and Th2 cytokine production, both of which have the potential to attenuate antiviral immune responses. Overall, compared to other γ-chain cytokines, IL-15 had the most favorable profile for boosting antiviral cell-mediated immunity

  6. Ureaplasma Species Differentially Modulate Pro- and Anti-Inflammatory Cytokine Responses in Newborn and Adult Human Monocytes Pushing the State Toward Pro-Inflammation

    Science.gov (United States)

    Glaser, Kirsten; Silwedel, Christine; Fehrholz, Markus; Waaga-Gasser, Ana M.; Henrich, Birgit; Claus, Heike; Speer, Christian P.

    2017-01-01

    Background: Ureaplasma species have been associated with chorioamnionitis and preterm birth and have been implicated in the pathogenesis of neonatal short and long-term morbidity. However, being mostly commensal bacteria, controversy remains on the pro-inflammatory capacity of Ureaplasma. Discussions are ongoing on the incidence and impact of prenatal, perinatal, and postnatal infection. The present study addressed the impact of Ureaplasma isolates on monocyte-driven inflammation. Methods: Cord blood monocytes of term neonates and adult monocytes, either native or LPS-primed, were cultured with Ureaplasma urealyticum (U. urealyticum) serovar 8 (Uu8) and Ureaplasma parvum serovar 3 (Up3). Using qRT-PCR, cytokine flow cytometry, and multi-analyte immunoassay, we assessed mRNA and protein expression of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-8, IL-12p40, IL-10, and IL-1 receptor antagonist (IL-1ra) as well as Toll-like receptor (TLR) 2 and TLR4. Results: Uu8 and Up3 induced mRNA expression and protein release of TNF-α, IL-1β and IL-8 in term neonatal and adult monocytes (p Ureaplasma-stimulated cells paralleled those results. Ureaplasma-induced cytokine levels did not significantly differ from LPS-mediated levels except for lower intracellular IL-1β in adult monocytes (Uu8: p ureaplasmas did not induce IL-12p40 response and promoted lower amounts of anti-inflammatory IL-10 and IL-1ra than LPS, provoking a cytokine imbalance more in favor of pro-inflammation (IL-1β/IL-10, IL-8/IL-10 and IL-8/IL-1ra: p Ureaplasma isolates in human monocytes. Stimulating pro-inflammatory cytokine responses while hardly inducing immunomodulatory and anti-inflammatory cytokines, ureaplasmas might push monocyte immune responses toward pro-inflammation. Inhibition of LPS-induced cytokines in adult monocytes in contrast to sustained inflammation in term neonatal monocytes indicates a differential modulation of host immune responses to a second stimulus. Modification of

  7. Toll-Like Receptors and Cytokines as Surrogate Biomarkers for Evaluating Vaginal Immune Response following Microbicide Administration

    Directory of Open Access Journals (Sweden)

    Sadhana M. Gupta

    2008-01-01

    Full Text Available Topical microbicides are intended for frequent use by women in reproductive age. Hence, it is essential to evaluate their impact on mucosal immune function in the vagina. In the present study, we evaluated nisin, a naturally occurring antimicrobial peptide (AMP, for its efficacy as an intravaginal microbicide. Its effect on the vaginal immune function was determined by localizing Toll-like receptors (TLRs-3, 9 and cytokines (IL-4, 6 , 10 and TNF-α in the rabbit cervicovaginal epithelium following intravaginal administration of high dose of nisin gel for 14 consecutive days. The results revealed no alteration in the expression of TLRs and cytokines at both protein and mRNA levels. However, in SDS gel-treated group, the levels were significantly upregulated with the induction of NF-κB signalling cascade. Thus, TLRs and cytokines appear as sensitive indicators for screening immunotoxic potential of candidate microbicides.

  8. Toll-like receptors and cytokines as surrogate biomarkers for evaluating vaginal immune response following microbicide administration.

    Science.gov (United States)

    Gupta, Sadhana M; Aranha, Clara C; Mohanty, Madhu C; Reddy, K V R

    2008-01-01

    Topical microbicides are intended for frequent use by women in reproductive age. Hence, it is essential to evaluate their impact on mucosal immune function in the vagina. In the present study, we evaluated nisin, a naturally occurring antimicrobial peptide (AMP), for its efficacy as an intravaginal microbicide. Its effect on the vaginal immune function was determined by localizing Toll-like receptors (TLRs-3, 9) and cytokines (IL-4, 6 , 10 and TNF-alpha) in the rabbit cervicovaginal epithelium following intravaginal administration of high dose of nisin gel for 14 consecutive days. The results revealed no alteration in the expression of TLRs and cytokines at both protein and mRNA levels. However, in SDS gel-treated group, the levels were significantly upregulated with the induction of NF-kappaB signalling cascade. Thus, TLRs and cytokines appear as sensitive indicators for screening immunotoxic potential of candidate microbicides.

  9. A possibilistic approach for transient identification with 'don't know' response capability optimized by genetic algorithm

    International Nuclear Information System (INIS)

    Almeida, Jose Carlos S. de; Schirru, Roberto; Pereira, Claudio M.N.A.; Universidade Federal, Rio de Janeiro, RJ

    2002-01-01

    This work describes a possibilistic approach for transient identification based on the minimum centroids set method, proposed in previous work, optimized by genetic algorithm. The idea behind this method is to split the complex classification problem into small and simple ones, so that the performance in the classification can be increased. In order to accomplish that, a genetic algorithm is used to learn, from realistic simulated data, the optimized time partitions, which the robustness and correctness in the classification are maximized. The use of a possibilistic classification approach propitiates natural and consistent classification rules, leading naturally to a good heuristic to handle the 'don't know 'response, in case of unrecognized transient, which is fairly desirable in transient classification systems where safety is critical. Application of the proposed approach to a nuclear transient indentification problem reveals good capability of the genetic algorithm in learning optimized possibilistic classification rules for efficient diagnosis including 'don't know' response. Obtained results are shown and commented. (author)

  10. A role for autoantibodies in enhancement of pro-inflammatory cytokine responses to a self-antigen, thyroid peroxidase

    DEFF Research Database (Denmark)

    Nielsen, Claus H; Brix, Thomas H; Leslie, R Graham Q

    2009-01-01

    The role of thyroid peroxidase (TPO) antibodies (TPOAbs) in the pathogenesis of autoimmune thyroid disease is unclear. We selected sera with a high concentration of TPOAbs from eleven patients with Hashimoto's thyroiditis (HT), ten healthy monozygotic co-twins to HT patients, and twelve healthy...... individuals with no familiar disposition to AITD, and mixed each serum with normal mononuclear cells (MNCs). Following challenge with TPO, the MNCs' production of the pro-inflammatory cytokines TNF-alpha, IL-6 and IFN-gamma, and the anti-inflammatory cytokine IL-10, correlated with the TPOAb content...

  11. Examination of epithelial tissue cytokine response to natural peste des petits ruminants virus (PPRV) infection in sheep and goats by immunohistochemistry.

    Science.gov (United States)

    Atmaca, H T; Kul, O

    2012-01-01

    In this study, we aimed to evaluate expression of IL-4, IL-10, TNF-α, IFN-γ and iNOS in lingual, buccal mucosa and lung epithelial tissue using immunoperoxidase technique and to compare with the tissues of control animals. The tissues used in the study were collected from 17 PPRV-affected and 5 healthy sheep and goats. In PPRV positive animals, the lungs, lingual and buccal mucosa had significantly higher iNOS, IFN-γ and TNF-α expressions compared to control group animals. There was no significant difference between PPRV positive and control groups for IL-4 and IL-10 expressions of epithelial tissues. In conclusion, the epithelial tissues infected by PPRV showed significant iNOS, IFN-γ and TNF-α expressions and they might play an important role in the initiation and regulation of cytokine response, as they take place in the first host barrier to be in contact with PPRV. It is suggested that the more epithelial damage produced by PPRV the more cytokine response may result in the infected epithelial cells. The first demonstration of iNOS expression and epithelial cytokine response to PPRV in natural cases is important because it may contribute to an early initiation of systemic immunity against PPRV infection, in addition to direct elimination of the virus during the initial epithelial phase of the infection.

  12. Bronchial and nasal responsiveness in atopic asthma and allergic rhinitis patients: Relationship of local responsiveness to cytokine production by peripheral blood mononuclear cells

    Directory of Open Access Journals (Sweden)

    Keiji Maeda

    1998-01-01

    Full Text Available To investigate the relationship between local responsiveness and allergic symptoms, bronchial and nasal responsiveness were measured in the following four groups of subjects: (i bronchial asthma patients with serum house dust mite (HDM-specific IgE antibody; (ii allergic rhinitis patients with serum HDM-specific IgE antibody; (iii normal control subjects with HDM-specific IgE antibody; and (iv normal control subjects without IgE antibody specific for 10 common aero-allergens. Bronchial hyperresponsiveness was detected in all subjects with asthma (group 1 and in some subjects from groups 2 and 3, but not in subjects from group 4. Nasal hyperresponsiveness was found in all subjects with allergic rhinitis (group 2 and in some subjects from groups 1 and 3, but not in subjects from group 4. These findings indicate that local hyperresponsiveness of the non-diseased organ is influenced by an individual's atopic status. Interleukin (IL-4 and IL-5 production by peripheral blood mononuclear cells (PBMC was measured after stimulation with HDM in groups 1, 2 and 3 and was found to be similar in all three groups. A correlation between bronchial hyperresponsiveness and in vitro cytokine production was noted in asthma patients. These results suggest that the capacity of IL-4 or IL-5 production by PBMC may reflect local hyperresponsiveness in case of asthma.

  13. Genome-wide association study of genetic variants in LPS-stimulated IL-6, IL-8, IL-10, IL-1ra and TNF-α cytokine response in a Danish Cohort

    DEFF Research Database (Denmark)

    Larsen, Margit Hørup; Albrechtsen, Anders; Thørner, Lise Wegner

    2013-01-01

    Cytokine response plays a vital role in various human lipopolysaccharide (LPS) infectious and inflammatory diseases. This study aimed to find genetic variants that might affect the levels of LPS-induced interleukin (IL)-6, IL-8, IL-10, IL-1ra and tumor necrosis factor (TNF)-α cytokine production....

  14. The utility of the historical record for assessing the transient climate response to cumulative emissions

    Science.gov (United States)

    Friedlingstein, Pierre

    2018-01-01

    The historical observational record offers a way to constrain the relationship between cumulative carbon dioxide emissions and global mean warming. We use a standard detection and attribution technique, along with observational uncertainties to estimate the all-forcing or ‘effective’ transient climate response to cumulative emissions (TCRE) from the observational record. Accounting for observational uncertainty and uncertainty in historical non-CO2 radiative forcing gives a best-estimate from the historical record of 1.84°C/TtC (1.43–2.37°C/TtC 5–95% uncertainty) for the effective TCRE and 1.31°C/TtC (0.88–2.60°C/TtC 5–95% uncertainty) for the CO2-only TCRE. While the best-estimate TCRE lies in the lower half of the IPCC likely range, the high upper bound is associated with the not-ruled-out possibility of a strongly negative aerosol forcing. Earth System Models have a higher effective TCRE range when compared like-for-like with the observations over the historical period, associated in part with a slight underestimate of diagnosed cumulative emissions relative to the observational best-estimate, a larger ensemble mean-simulated CO2-induced warming, and rapid post-2000 non-CO2 warming in some ensemble members. This article is part of the theme issue ‘The Paris Agreement: understanding the physical and social challenges for a warming world of 1.5°C above pre-industrial levels'. PMID:29610381

  15. The utility of the historical record for assessing the transient climate response to cumulative emissions

    Science.gov (United States)

    Millar, Richard J.; Friedlingstein, Pierre

    2018-05-01

    The historical observational record offers a way to constrain the relationship between cumulative carbon dioxide emissions and global mean warming. We use a standard detection and attribution technique, along with observational uncertainties to estimate the all-forcing or `effective' transient climate response to cumulative emissions (TCRE) from the observational record. Accounting for observational uncertainty and uncertainty in historical non-CO2 radiative forcing gives a best-estimate from the historical record of 1.84°C/TtC (1.43-2.37°C/TtC 5-95% uncertainty) for the effective TCRE and 1.31°C/TtC (0.88-2.60°C/TtC 5-95% uncertainty) for the CO2-only TCRE. While the best-estimate TCRE lies in the lower half of the IPCC likely range, the high upper bound is associated with the not-ruled-out possibility of a strongly negative aerosol forcing. Earth System Models have a higher effective TCRE range when compared like-for-like with the observations over the historical period, associated in part with a slight underestimate of diagnosed cumulative emissions relative to the observational best-estimate, a larger ensemble mean-simulated CO2-induced warming, and rapid post-2000 non-CO2 warming in some ensemble members. This article is part of the theme issue `The Paris Agreement: understanding the physical and social challenges for a warming world of 1.5°C above pre-industrial levels'.

  16. Low temperature transient response and electroluminescence characteristics of OLEDs based on Alq{sub 3}

    Energy Technology Data Exchange (ETDEWEB)

    Yuan, Chao [Key Laboratory of Semiconductor Material Sciences, Beijing Key Laboratory of Low Dimensional Semiconductor Materials and Devices, Institute of Semiconductors, Chinese Academy of Sciences, Beijing 100083 (China); College of Materials Science and Optoelectronic Devices, University of Chinese Academy of Sciences, Beijing 100049 (China); Guan, Min, E-mail: guanmin@semi.ac.cn [Key Laboratory of Semiconductor Material Sciences, Beijing Key Laboratory of Low Dimensional Semiconductor Materials and Devices, Institute of Semiconductors, Chinese Academy of Sciences, Beijing 100083 (China); Zhang, Yang [Key Laboratory of Semiconductor Material Sciences, Beijing Key Laboratory of Low Dimensional Semiconductor Materials and Devices, Institute of Semiconductors, Chinese Academy of Sciences, Beijing 100083 (China); College of Materials Science and Optoelectronic Devices, University of Chinese Academy of Sciences, Beijing 100049 (China); Li, Yiyang; Liu, Shuangjie [Key Laboratory of Semiconductor Material Sciences, Beijing Key Laboratory of Low Dimensional Semiconductor Materials and Devices, Institute of Semiconductors, Chinese Academy of Sciences, Beijing 100083 (China); Zeng, Yiping [Key Laboratory of Semiconductor Material Sciences, Beijing Key Laboratory of Low Dimensional Semiconductor Materials and Devices, Institute of Semiconductors, Chinese Academy of Sciences, Beijing 100083 (China); College of Materials Science and Optoelectronic Devices, University of Chinese Academy of Sciences, Beijing 100049 (China)

    2017-08-15

    Highlights: • The dependency relation between transmission rate and electron transport layer is revealed. • The critical temperature points for the influence of luminescent materials and injection barriers on delay time are found. • The influence of light-emitting material and injection layer on carrier accumulation is quantified. - Abstract: In this work, the organic light-emitting diodes (OLEDs) based on Alq{sub 3} are fabricated. In order to make clear the transport mechanism of carriers in organic light-emitting devices at low temperature, detailed electroluminescence transient response and the current-voltage–luminescence (I–V–L) characteristics under different temperatures in those OLEDs are investigated. It founds that the acceleration of brightness increases with increasing temperature is maximum when the temperature is 200 K and it is mainly affected by the electron transport layer (Alq{sub 3}). The MoO{sub 3} injection layer and the electroluminescent layer have great influence on the delay time when the temperature is 200 K. Once the temperature is greater than 250 K, the delay time is mainly affected by the MoO{sub 3} injection layer. On the contrary, the fall time is mainly affected by the electroluminescent material. The V{sub f} is the average growth rate of fall time when the temperature increases 1 K which represents the accumulation rate of carriers. The difference between V{sub f} caused by the MoO{sub 3} injection layer is 0.52 us/K and caused by the electroluminescent material Ir(ppy){sub 3} is 0.73 us/K.

  17. A neural model for transient identification in dynamic processes with 'don't know' response

    Energy Technology Data Exchange (ETDEWEB)

    Mol, Antonio C. de A. E-mail: mol@ien.gov.br; Martinez, Aquilino S. E-mail: aquilino@lmp.ufrj.br; Schirru, Roberto E-mail: schirru@lmp.ufrj.br

    2003-09-01

    This work presents an approach for neural network based transient identification which allows either dynamic identification or a 'don't know' response. The approach uses two 'jump' multilayer neural networks (NN) trained with the backpropagation algorithm. The 'jump' network is used because it is useful to dealing with very complex patterns, which is the case of the space of the state variables during some abnormal events. The first one is responsible for the dynamic identification. This NN uses, as input, a short set (in a moving time window) of recent measurements of each variable avoiding the necessity of using starting events. The other one is used to validate the instantaneous identification (from the first net) through the validation of each variable. This net is responsible for allowing the system to provide a 'don't know' response. In order to validate the method, a Nuclear Power Plant (NPP) transient identification problem comprising 15 postulated accidents, simulated for a pressurized water reactor (PWR), was proposed in the validation process it has been considered noisy data in order to evaluate the method robustness. Obtained results reveal the ability of the method in dealing with both dynamic identification of transients and correct 'don't know' response. Another important point studied in this work is that the system has shown to be independent of a trigger signal which indicates the beginning of the transient, thus making it robust in relation to this limitation.

  18. Modulation of Female Genital Tract-Derived Dendritic Cell Migration and Activation in Response to Inflammatory Cytokines and Toll-Like Receptor Agonists.

    Science.gov (United States)

    Shey, Muki S; Maharaj, Niren; Archary, Derseree; Ngcapu, Sinaye; Garrett, Nigel; Abdool Karim, Salim; Passmore, Jo-Ann S

    2016-01-01

    HIV transmission across the genital mucosa is a major mode of new HIV infections in women. The probability of infection may be influenced by several factors including recruitment and activation of HIV target cells, such as dendritic cells (DCs) and cytokine production, associated with genital inflammation. We evaluated the role of inflammatory cytokines and TLR signaling in migration and activation of genital tract DCs in the human cervical explant model. Hysterectomy tissues from 10 HIV-negative and 7 HIV-positive donor women were separated into ecto- and endocervical explants, and incubated with inflammatory cytokines (TNF-α, IL-1β, IL-8, MIP-1β) or agonists for TLR4 (LPS), TLR2/1 (PAM3) and TLR7/8 (R848). Migration (frequency) and activation (HLA-DR expression) of myeloid and plasmacytoid DCs and Langerhans cells were measured by flow cytometry. We observed that cytokines, LPS and PAM3 induced activation of migrating myeloid and plasmacytoid DCs. LPS induced a 3.6 fold lower levels of migration of plasmacytoid DCs from HIV-infected women compared with HIV-uninfected women (median activation indices of 2.932 vs 0.833). There was however a 4.5 fold increase in migration of Langerhans cells in HIV-infected compared with HIV-uninfected women in response to cytokines (median activation indices of 3.539 vs 0.77). Only TLR agonists induced migration and activation of DCs from endocervical explants. Hormonal contraception use was associated with an increase in activation of DC subsets in the endo and ectocervical explants. We conclude that inflammatory signals in the female genital tract induced DC migration and activation, with possible important implications for HIV susceptibility of cervical tissues.

  19. Modulation of Female Genital Tract-Derived Dendritic Cell Migration and Activation in Response to Inflammatory Cytokines and Toll-Like Receptor Agonists.

    Directory of Open Access Journals (Sweden)

    Muki S Shey

    Full Text Available HIV transmission across the genital mucosa is a major mode of new HIV infections in women. The probability of infection may be influenced by several factors including recruitment and activation of HIV target cells, such as dendritic cells (DCs and cytokine production, associated with genital inflammation. We evaluated the role of inflammatory cytokines and TLR signaling in migration and activation of genital tract DCs in the human cervical explant model. Hysterectomy tissues from 10 HIV-negative and 7 HIV-positive donor women were separated into ecto- and endocervical explants, and incubated with inflammatory cytokines (TNF-α, IL-1β, IL-8, MIP-1β or agonists for TLR4 (LPS, TLR2/1 (PAM3 and TLR7/8 (R848. Migration (frequency and activation (HLA-DR expression of myeloid and plasmacytoid DCs and Langerhans cells were measured by flow cytometry. We observed that cytokines, LPS and PAM3 induced activation of migrating myeloid and plasmacytoid DCs. LPS induced a 3.6 fold lower levels of migration of plasmacytoid DCs from HIV-infected women compared with HIV-uninfected women (median activation indices of 2.932 vs 0.833. There was however a 4.5 fold increase in migration of Langerhans cells in HIV-infected compared with HIV-uninfected women in response to cytokines (median activation indices of 3.539 vs 0.77. Only TLR agonists induced migration and activation of DCs from endocervical explants. Hormonal contraception use was associated with an increase in activation of DC subsets in the endo and ectocervical explants. We conclude that inflammatory signals in the female genital tract induced DC migration and activation, with possible important implications for HIV susceptibility of cervical tissues.

  20. A numerical algorithm to evaluate the transient response for a synchronous scanning streak camera using a time-domain Baum–Liu–Tesche equation

    Energy Technology Data Exchange (ETDEWEB)

    Pei, Chengquan [Key Laboratory for Physical Electronics and Devices of the Ministry of Education, Xi' an Jiaotong University, Xi’an 710049 (China); Tian, Jinshou [Xi' an Institute of Optics and Precision Mechanics, Chinese Academy of Sciences, Xi' an 710119 (China); Wu, Shengli, E-mail: slwu@mail.xjtu.edu.cn [Key Laboratory for Physical Electronics and Devices of the Ministry of Education, Xi' an Jiaotong University, Xi’an 710049 (China); He, Jiai [School of Computer and Communication, Lanzhou University of Technology, Lanzhou, Gansu 730050 (China); Liu, Zhen [Key Laboratory for Physical Electronics and Devices of the Ministry of Education, Xi' an Jiaotong University, Xi’an 710049 (China)

    2016-10-01

    The transient response is of great influence on the electromagnetic compatibility of synchronous scanning streak cameras (SSSCs). In this paper we propose a numerical method to evaluate the transient response of the scanning deflection plate (SDP). First, we created a simplified circuit model for the SDP used in an SSSC, and then derived the Baum–Liu–Tesche (BLT) equation in the frequency domain. From the frequency-domain BLT equation, its transient counterpart was derived. These parameters, together with the transient-BLT equation, were used to compute the transient load voltage and load current, and then a novel numerical method to fulfill the continuity equation was used. Several numerical simulations were conducted to verify this proposed method. The computed results were then compared with transient responses obtained by a frequency-domain/fast Fourier transform (FFT) method, and the accordance was excellent for highly conducting cables. The benefit of deriving the BLT equation in the time domain is that it may be used with slight modifications to calculate the transient response and the error can be controlled by a computer program. The result showed that the transient voltage was up to 1000 V and the transient current was approximately 10 A, so some protective measures should be taken to improve the electromagnetic compatibility.

  1. A numerical algorithm to evaluate the transient response for a synchronous scanning streak camera using a time-domain Baum–Liu–Tesche equation

    International Nuclear Information System (INIS)

    Pei, Chengquan; Tian, Jinshou; Wu, Shengli; He, Jiai; Liu, Zhen

    2016-01-01

    The transient response is of great influence on the electromagnetic compatibility of synchronous scanning streak cameras (SSSCs). In this paper we propose a numerical method to evaluate the transient response of the scanning deflection plate (SDP). First, we created a simplified circuit model for the SDP used in an SSSC, and then derived the Baum–Liu–Tesche (BLT) equation in the frequency domain. From the frequency-domain BLT equation, its transient counterpart was derived. These parameters, together with the transient-BLT equation, were used to compute the transient load voltage and load current, and then a novel numerical method to fulfill the continuity equation was used. Several numerical simulations were conducted to verify this proposed method. The computed results were then compared with transient responses obtained by a frequency-domain/fast Fourier transform (FFT) method, and the accordance was excellent for highly conducting cables. The benefit of deriving the BLT equation in the time domain is that it may be used with slight modifications to calculate the transient response and the error can be controlled by a computer program. The result showed that the transient voltage was up to 1000 V and the transient current was approximately 10 A, so some protective measures should be taken to improve the electromagnetic compatibility.

  2. Agmatine Reverses Sub-chronic Stress induced Nod-like Receptor Protein 3 (NLRP3) Activation and Cytokine Response in Rats.

    Science.gov (United States)

    Sahin, Ceren; Albayrak, Ozgur; Akdeniz, Tuğba F; Akbulut, Zeynep; Yanikkaya Demirel, Gulderen; Aricioglu, Feyza

    2016-10-01

    The activation of Nod-like receptor protein 3 (NLRP3) has lately been implicated in stress and depression as an initiator mechanism required for the production of interleukin (IL)-1β and IL-18. Agmatine, an endogenous polyamine widely distributed in mammalian brain, is a novel neurotransmitter/neuromodulator, with antistress, anxiolytic and antidepressant-like effects. In this study, we examined the effect of exogenously administered agmatine on NLRP3 inflammasome pathway/cytokine responses in rats exposed to restraint stress for 7 days. The rats were divided into three groups: stress, stress+agmatine (40 mg/kg; i.p.) and control groups. Agmatine significantly down-regulated the gene expressions of all stress-induced NLRP3 inflammasome components (NLRP3, NF-κB, PYCARD, caspase-1, IL-1β and IL-18) in the hippocampus and prefrontal cortex (PFC) and reduced pro-inflammatory cytokine levels not only in both brain regions, but also in serum. Stress-reduced levels of IL-4 and IL-10, two major anti-inflammatory cytokines, were restored back to normal by agmatine treatment in the PFC. The findings of the present study suggest that stress-activated NLRP3 inflammasome and cytokine responses are reversed by an acute administration of agmatine. Whether antidepressant-like effect of agmatine can somehow, at least partially, be mediated by the inhibition of NLRP3 inflammasome cascade and relevant inflammatory responses requires further studies in animal models of depression. © 2016 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

  3. The SaeR/S gene regulatory system induces a pro-inflammatory cytokine response during Staphylococcus aureus infection.

    Directory of Open Access Journals (Sweden)

    Robert L Watkins

    Full Text Available Community-associated methicillin-resistant Staphylococcus aureus accounts for a large portion of the increased staphylococcal disease incidence and can cause illness ranging from mild skin infections to rapidly fatal sepsis syndromes. Currently, we have limited understanding of S. aureus-derived mechanisms contributing to bacterial pathogenesis and host inflammation during staphylococcal disease. Herein, we characterize an influential role for the saeR/S two-component gene regulatory system in mediating cytokine induction using mouse models of S. aureus pathogenesis. Invasive S. aureus infection induced the production of localized and systemic pro-inflammatory cytokines, including tumor necrosis factor alpha (TNF-α, interferon gamma (IFN-γ, interleukin (IL-6 and IL-2. In contrast, mice infected with an isogenic saeR/S deletion mutant demonstrated significantly reduced pro-inflammatory cytokine levels. Additionally, secreted factors influenced by saeR/S elicited pro-inflammatory cytokines in human blood ex vivo. Our study further demonstrated robust saeR/S-mediated IFN-γ production during both invasive and subcutaneous skin infections. Results also indicated a critical role for saeR/S in promoting bacterial survival and enhancing host mortality during S. aureus peritonitis. Taken together, this study provides insight into specific mechanisms used by S. aureus during staphylococcal disease and characterizes a relationship between a bacterial global regulator of virulence and the production of pro-inflammatory mediators.

  4. Modulation of murine cellular immune response and cytokine production by salivary gland lysate of three sand fly species

    Czech Academy of Sciences Publication Activity Database

    Rohoušová, Iva; Volf, P.; Lipoldová, Marie

    2005-01-01

    Roč. 12, č. 27 (2005), s. 469-473 ISSN 0141-9838 R&D Projects: GA ČR(CZ) GA310/03/1381 Institutional research plan: CEZ:AV0Z5052915 Keywords : cytokine production * Lutzomyia * Phlebotomus Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 1.445, year: 2005

  5. Sustained and transient oscillations and chaos induced by delayed antiviral immune response in an immunosuppressive infection model.

    Science.gov (United States)

    Shu, Hongying; Wang, Lin; Watmough, James

    2014-01-01

    Sustained and transient oscillations are frequently observed in clinical data for immune responses in viral infections such as human immunodeficiency virus, hepatitis B virus, and hepatitis C virus. To account for these oscillations, we incorporate the time lag needed for the expansion of immune cells into an immunosuppressive infection model. It is shown that the delayed antiviral immune response can induce sustained periodic oscillations, transient oscillations and even sustained aperiodic oscillations (chaos). Both local and global Hopf bifurcation theorems are applied to show the existence of periodic solutions, which are illustrated by bifurcation diagrams and numerical simulations. Two types of bistability are shown to be possible: (i) a stable equilibrium can coexist with another stable equilibrium, and (ii) a stable equilibrium can coexist with a stable periodic solution.

  6. DEFORM-4: fuel pin characterization and transient response in the SAS4A accident analysis code system

    International Nuclear Information System (INIS)

    Miles, K.J.; Hill, D.J.

    1986-01-01

    The DEFORM-4 module is the segment of the SAS4A Accident Analysis Code System that calculates the fuel pin characterization in response to a steady state irradiation history, thereby providing the initial conditions for the transient calculation. The various phenomena considered include fuel porosity migration, fission gas bubble induced swelling, fuel cracking and healing, fission gas release, cladding swelling, and the thermal-mechanical state of the fuel and cladding. In the transient state, the module continues the thermal-mechanical response calculation, including fuel melting and central cavity pressurization, until cladding failure is predicted and one of the failed fuel modules is initiated. Comparisons with experimental data have demonstrated the validity of the modeling approach

  7. Transient identification system with noising data and 'don't know' response; Sistema de identificacao de transientes com inclusao de ruidos e indicacao de eventos desconhecidos

    Energy Technology Data Exchange (ETDEWEB)

    Mol, Antonio C. de A. [Instituto de Engenharia Nuclear (IEN), Rio de Janeiro, RJ (Brazil). Div. de Confiabilidade Humana; Martinez, Aquilino S.; Schirru, Roberto [Universidade Federal, Rio de Janeiro, RJ (Brazil). Coordenacao dos Programas de Pos-graduacao de Engenharia. Programa de Engenharia Nuclear

    2002-07-01

    In the last years, many different approaches based on neural network (NN) has been proposed for transient identification in nuclear power plants (NPP). Some of them focus the dynamic identification using recurrent neural networks however, they are not able to deal with unrecognized transients. Other kind of solution uses competitive learning in order to allow the 'don't know' response. In this case dynamic, dynamic features are not well represented. This work presents a new approach for neural network based transient identification which allows either dynamic identification and 'don't know'response. Such approach uses two multilayer neural networks trained with backpropagation algorithm. The first one is responsible for the dynamic identification. This NN uses, a short set (in a movable time window) of recent measurements of each variable avoiding the necessity of using starting events. The other one is used to validate the instantaneous identification (from the first net) through the validation of each variable. This net is responsible for allowing the system to provide 'don't know' response. In order to validate the method a NPP transient identification problem comprising 15 postulated accidents, simulated for a pressurized water reactor, was proposed in the validation process it has been considered noising data in other to evaluate the method robustness. Obtained results reveal the ability of the method in dealing with both dynamic identification of transients and correct 'don't know' response. In order to validate the method, a NPP transient identification problem comprising 15 postulated accidents simulated for a pressurized water reactor, was proposed in the validation process it has been considered noising data in order to evaluate the method robustness. Obtained results reveal the ability of the method in dealing with both dynamic identification of transients and correct 'don't know

  8. Dayside magnetospheric and ionospheric responses to a foreshock transient on June 25, 2008: 2. 2-D evolution based on dayside auroral imaging

    OpenAIRE

    Wang, Boyi; Nishimura, Yukitoshi; Hietala, Heli; Shen, Xiao-Chen; Shi, Quanqi; Zhang, Hui; Lyons, Larry; Zou, Ying; Angelopoulos, Vassilis; Ebihara, Yusuke; Weatherwax, Allan

    2018-01-01

    The foreshock region involves localized and transient structures such as foreshock cavities and hot flow anomalies due to solar wind-bow shock interactions, and foreshock transients have been shown to lead to magnetospheric and ionospheric responses. In this paper, the interaction between a foreshock transient and the magnetosphere-ionosphere system is investigated using dayside aurora imagers revealing structures and propagation in greater detail than previously possible. A foreshock transie...

  9. Circulating cytokines and procalcitonin in acute Q fever granulomatous hepatitis with poor response to antibiotic and short-course steroid therapy: a case report

    Directory of Open Access Journals (Sweden)

    Chang Lin-Li

    2010-07-01

    Full Text Available Abstract Background Q fever is a zoonosis distributed worldwide that is caused by Coxiella burnetii infection and the defervescence usually occurs within few days of appropriate antibiotic therapy. Whether the changes of cytokine levels are associated with acute Q fever with persistent fever despite antibiotic therapy had not been investigated before. Case Presentation We report a rare case of acute Q fever granulomatous hepatitis remained pyrexia despite several antibiotic therapy and 6-day course of oral prednisolone. During the 18-month follow-up, the investigation of the serum cytokines profile and procalcitonin (PCT revealed that initially elevated levels of interleukin-2 (IL-2, IL-8, IL-10, and PCT decreased gradually, but the IL-6 remained in low titer. No evidence of chronic Q fever was identified by examinations of serum antibodies against C. burnetii and echocardiography. Conclusions The changes of cytokine levels may be associated with acute Q fever with poor response to treatment and PCT may be an indicator for monitoring the response to treatment.

  10. Depressive-like behavior, its sensitization, social buffering, and altered cytokine responses in rhesus macaques moved from outdoor social groups to indoor housing.

    Science.gov (United States)

    Hennessy, Michael B; Chun, Katie; Capitanio, John P

    2017-02-01

    Psychosocial stressors appear to promote the onset of depressive illness through activation and sensitization of inflammatory mechanisms. Here, adult male rhesus monkeys brought from large outdoor social groups to indoor housing for 8 days reliably exhibited a hunched, depressive-like posture. When rehoused indoors a second 8 days about 2 weeks later, monkeys housed alone, but not those with an affiliative partner, showed sensitization of the depressive-like hunched posture. Housing indoors also affected circulating pro-inflammatory cytokines: IL-1β showed increased responsiveness to immune challenge, and IL-1β and TNF-α showed reduced suppression by dexamethasone. Sensitivity of the anti-inflammatory cytokine IL-10 to immune challenge exhibited a relative increase from the first to the second round of indoor housing in animals housed in pairs, and a relative decrease in animals housed alone. Cytokine levels during indoor housing were positively correlated with duration of depressive-like behavior. Plasma cortisol levels increased but did not differentiate housing conditions or rounds. Results demonstrate a rapid induction and sensitization of depressive-like behavior to indoor individual housing, social buffering of sensitization, and associated inflammatory responses. This paradigm may provide a practical nonhuman primate model for examining inflammatory-mediated consequences of psychosocial stressors on depression and possible social buffering of these effects.

  11. HMGB1/RAGE Signaling and Pro-Inflammatory Cytokine Responses in Non-HIV Adults with Active Pulmonary Tuberculosis.

    Directory of Open Access Journals (Sweden)

    Grace Lui

    Full Text Available We aimed to study the pathogenic roles of High-Mobility Group Box 1 (HMGB1 / Receptor-for-Advanced-Glycation-End-products (RAGE signaling and pro-inflammatory cytokines in patients with active pulmonary tuberculosis (PTB.A prospective study was conducted among non-HIV adults newly-diagnosed with active PTB at two acute-care hospitals (n = 80; age-and-sex matched asymptomatic individuals (tested for latent TB were used for comparison (n = 45. Plasma concentrations of 8 cytokines/chemokines, HMGB1, soluble-RAGE, and transmembrane-RAGE expressed on monocytes/dendritic cells, were measured. Gene expression (mRNA of HMGB1, RAGE, and inflammasome-NALP3 was quantified. Patients' PBMCs were stimulated with recombinant-HMGB1 and MTB-antigen (lipoarabinomannan for cytokine induction ex vivo.In active PTB, plasma IL-8/CXCL8 [median(IQR, 6.0(3.6-15.1 vs 3.6(3.6-3.6 pg/ml, P<0.001] and IL-6 were elevated, which significantly correlated with mycobacterial load, extent of lung consolidation (rs +0.509, P<0.001, severity-score (rs +0.317, P = 0.004, and fever and hospitalization durations (rs +0.407, P<0.001. IL-18 and sTNFR1 also increased. Plasma IL-8/CXCL8 (adjusted OR 1.12, 95%CI 1.02-1.23 per unit increase, P = 0.021 and HMGB1 (adjusted OR 1.42 per unit increase, 95%CI 1.08-1.87, P = 0.012 concentrations were independent predictors for respiratory failure, as well as for ICU admission/death. Gene expression of HMGB1, RAGE, and inflammasome-NALP3 were upregulated (1.2-2.8 fold. Transmembrane-RAGE was increased, whereas the decoy soluble-RAGE was significantly depleted. RAGE and HMGB1 gene expressions positively correlated with cytokine levels (IL-8/CXCL8, IL-6, sTNFR1 and clinico-/radiographical severity (e.g. extent of consolidation rs +0.240, P = 0.034. Ex vivo, recombinant-HMGB1 potentiated cytokine release (e.g. TNF-α when combined with lipoarabinomannan.In patients with active PTB, HMGB1/RAGE signaling and pro-inflammatory cytokines may play important

  12. Transient and Steady-State Responses of an Asymmetric Nonlinear Oscillator

    Directory of Open Access Journals (Sweden)

    Alex Elías-Zúñiga

    2013-01-01

    oscillator that describes the motion of a damped, forced system supported symmetrically by simple shear springs on a smooth inclined bearing surface. We also use the percentage overshoot value to study the influence of damping and nonlinearity on the transient and steady-state oscillatory amplitudes.

  13. Transient changes of optical properties in semiconductors in response to femtosecond laser pulses

    Czech Academy of Sciences Publication Activity Database

    Tkachenko, V.; Medvedev, Nikita; Ziaja, B.

    2016-01-01

    Roč. 6, č. 9 (2016), 1-12, č. článku 238. ISSN 2076-3417 Institutional support: RVO:68378271 Keywords : free-electron lasers * transient optical properties Subject RIV: BM - Solid Matter Physics ; Magnetism Impact factor: 1.679, year: 2016

  14. Fast transient current response to switching events in short chains of molecular islands

    Czech Academy of Sciences Publication Activity Database

    Kalvová, Anděla; Špička, Václav; Velický, B.

    2013-01-01

    Roč. 26, č. 4 (2013), s. 773-777 ISSN 1557-1939 R&D Projects: GA ČR GAP204/12/0897 Institutional support: RVO:68378271 Keywords : nonequilibrium * molecular islands * initial correlations * transient currents Subject RIV: BE - Theoretical Physics Impact factor: 0.930, year: 2013

  15. Infant milk formulas differ regarding their allergenic activity and induction of T-cell and cytokine responses

    DEFF Research Database (Denmark)

    Hochwallner, H; Schulmeister, U; Swoboda, Ines

    2017-01-01

    BACKGROUND: Several hydrolyzed cow's milk (CM) formulas are available for avoidance of allergic reactions in CM-allergic children and for prevention of allergy development in high-risk infants. Our aim was to compare CM formulas regarding the presence of immunoreactive CM components, IgE reactivity......, allergenic activity, ability to induce T-cell proliferation, and cytokine secretion. METHODS: A blinded analysis of eight CM formulas, one nonhydrolyzed, two partially hydrolyzed (PH), four extensively hydrolyzed (EH), and one amino acid formula, using biochemical techniques and specific antibody probes...... was conducted. IgE reactivity and allergenic activity of the formulas were tested with sera from CM-allergic patients (n = 26) in RAST-based assays and with rat basophils transfected with the human FcεRI, respectively. The induction of T-cell proliferation and the secretion of cytokines in Peripheral blood...

  16. Kluyveromyces marxianus and Saccharomyces boulardii induce distinct levels of dendritic cell cytokine secretion and significantly different T cell responses In Vitro

    DEFF Research Database (Denmark)

    Smith, Ida Mosbech; Baker, Adam; Christensen, Jeffrey E

    2016-01-01

    induction of a Treg response characterized by robust IL-10 secretion. In addition, we blocked relevant DC surface receptors and investigated the stimulating properties of β-glucan containing yeast cell wall extracts. K. marxianus and S. boulardii induced distinct levels of DC cytokine secretion, primarily...... driven by Dectin-1 recognition of β-glucan components in their cell walls. Upon co-incubation of yeast exposed DCs and naive T cells, S. boulardii induced a potent IFNγ response indicating TH1 mobilization. In contrast, K. marxianus induced a response dominated by Foxp3+ Treg cells, a characteristic...... of the present study was to characterize the immune modulating properties of the food-related yeast Kluyveromyces marxianus in terms of adaptive immune responses indicating inflammation versus tolerance and to explore the mechanisms behind the observed responses. Benchmarking against a Saccharomyces boulardii...

  17. Cytokine and clinical response to Saccharomyces boulardii therapy in diarrhea-dominant irritable bowel syndrome: a randomized trial.

    Science.gov (United States)

    Abbas, Zaigham; Yakoob, Javed; Jafri, Wasim; Ahmad, Zubair; Azam, Zahid; Usman, Muhammad W; Shamim, Sara; Islam, Muhammad

    2014-06-01

    This preliminary study aimed to investigate the effects of the probiotic Saccharomyces boulardii on proinflammatory and anti-inflammatory cytokines in patients with diarrhea-dominant irritable bowel syndrome (IBS-D). The other objectives were to document any clinical improvement as judged by symptoms, quality of life, and histology. This was a randomized, double blind, placebo-controlled trial in which S. boulardii, 750 mg/day, or placebo was administered for 6 weeks in IBS-D patients, in addition to ispaghula husk standard treatment. Thirty-seven patients received S. boulardii and 35 patients received the placebo. As compared with placebo, the S. boulardii group showed a significant decrease in blood and tissue levels of proinflammatory cytokines interleukin-8 (IL-8) and tumor necrosis factor-α (PS. boulardii group. Although baseline histological findings were mild, an improvement was observed in the probiotic group in the lymphocyte and neutrophil infiltrates (P=0.017 and 0.018), epithelial mitosis (P=0.003), and intraepithelial lymphocytes (P=0.024). No serious adverse events were found in either group. S. boulardii with ispaghula husk was superior to placebo with ispaghula husk in improving the cytokine profile, histology, and quality of life of patients with IBS-D. These preliminary results need to be confirmed in a well-powered trial.

  18. Cord Blood Cells Responses to IL2, IL7 and IL15 Cytokines for mTOR Expression

    Directory of Open Access Journals (Sweden)

    Anahita Mohammadian

    2017-04-01

    Full Text Available Purpose: Mammalian target of rapamycin (mTORis important in hematopoiesis and affect cell growth,differentiation and survival. Although previous studies were identified the effect of cytokines on the mononuclear cells development however the cytokines effect on mTOR in cord blood mononuclear cells was unclear. The aim of this study was to evaluate mTOR expression in cord blood mononuclear and cord blood stem cells (CD34+ cells in culture conditions for lymphoid cell development. Methods: Isolation of The mononuclear cells (MNCs from umbilical cord blood were done with use of Ficollpaque density gradient. We evaluated cultured cord blood mononuclear and CD34+ cells in presece of IL2, IL7 and IL15 at distinct time points during 21 days by using flow cytometry. In this study, we presented the role of IL2, IL7 and IL15 on the expression of mTOR in cord blood cells. Results: mTOR expression were increased in peresence of IL2, IL7 and IL15 in day 14 and afterword reduced. However in persence of IL2 and IL15 expression of mTOR significantly reduced. mTOR expression in CD34+ cells decreased significantly from day7 to day 21 in culture. Conclusion: cytokines play important role in mTOR expression during hematopoiesis and development of cord blood mononuclear cells.

  19. Transient thermal response of a packed bed for energy storage unit utilizing phase change material: experimental and numerical study

    International Nuclear Information System (INIS)

    Bemansour, A.

    2006-01-01

    The present work concerns the numerical and experimental study of the transient response of a packed bed latent heat thermal energy storage system. Experiments were carried out to measures the transient temperature distributions inside a cylindrical bed, which is randomly packed with spheres having uniform sizes and encapsulated the paraffin wax as a phase change material (PCM), with air as a working fluid. A two-dimensional separate phases formulation is used to develop a numerical analysis of the transient response of the bed, considering the influence of both axial and radial thermal dispersion. The fluid energy equation was transformed by finite difference approximation and solved by alternating direction implicit scheme, while the PCM energy equation was solved using fully explicit scheme. This analysis can be applied for both charging and recovery modes and a broad range of Reynolds numbers. Measurements of both fluid and PCM temperature were conducted at different axial and radial positions and at different operating parameters. Experimental measurements of temperature distribution compare favorably with the numerical results over a broad range of Reynolds numbers.(Author)

  20. Difference in Pro-Inflammatory Cytokine Responses Induced in THP1 Cells by Particulate Matter Collected on Days with and without ASIAN Dust Storms

    Directory of Open Access Journals (Sweden)

    Masanari Watanabe

    2015-07-01

    Full Text Available The associations between particulate matter from Asian dust storms (ADS and health disorders differ among studies, and the underlying mechanisms remain unclear. In this study, ADS and non-ADS particles were tested for their potential to induce pro-inflammatory cytokines associated with adverse respiratory effects. Particulate matter was collected in Japan during four periods in 2013 (2 × ADS periods; 2 × non-ADS. THP1 cells were exposed to this particulate matter, and the levels of various interleukins (ILs, and tumor necrosis factor (TNF-α were measured. Levels of IL-2 increased significantly following exposure to all particulate matter samples (compared to levels in a solvent control. Increased levels of IL-10 and TNF-α were also observed following exposure to particles collected during three (one ADS and two non-ADS and two (one ADS and one non-ADS collection periods, respectively. Thus, the effects of particulate matter on cytokine responses differed according to collection period, and the effects of ADS particles differed for each ADS event. Additionally, the levels of pro-inflammatory cytokines induced by ADS particles were not always higher than those induced by non-ADS particles.

  1. Cytokine response during non-cerebral and cerebral malaria: evidence of a failure to control inflammation as a cause of death in African adults

    Directory of Open Access Journals (Sweden)

    Yakhya Dieye

    2016-05-01

    Full Text Available Background. With 214 million cases and 438,000 deaths in 2015, malaria remains one of the deadliest infectious diseases in tropical countries. Several species of the protozoan Plasmodium cause malaria. However, almost all the fatalities are due to Plasmodium falciparum, a species responsible for the severest cases including cerebral malaria. Immune response to Plasmodium falciparum infection is mediated by the production of pro-inflammatory cytokines, chemokines and growth factors whose actions are crucial for the control of the parasites. Following this response, the induction of anti-inflammatory immune mediators downregulates the inflammation thus preventing its adverse effects such as damages to various organs and death. Methods. We performed a retrospective, nonprobability sampling study using clinical data and sera samples from patients, mainly adults, suffering of non-cerebral or cerebral malaria in Dakar, Sénégal. Healthy individuals residing in the same area were included as controls. We measured the serum levels of 29 biomarkers including growth factors, chemokines, inflammatory and anti-inflammatory cytokines. Results. We found an induction of both pro- and anti-inflammatory immune mediators during malaria. The levels of pro-inflammatory biomarkers were higher in the cerebral malaria than in the non-cerebral malaria patients. In contrast, the concentrations of anti-inflammatory cytokines were comparable in these two groups or lower in CM patients. Additionally, four pro-inflammatory biomarkers were significantly increased in the deceased of cerebral malaria compared to the survivors. Regarding organ damage, kidney failure was significantly associated with death in adults suffering of cerebral malaria. Conclusions. Our results suggest that a poorly controlled inflammatory response determines a bad outcome in African adults suffering of cerebral malaria.

  2. Elevated cytokine responses to Vibrio harveyi infection in the Japanese pufferfish (Takifugu rubripes) treated with Lactobacillus paracasei spp. paracasei (06TCa22) isolated from the Mongolian dairy product.

    Science.gov (United States)

    Biswas, G; Korenaga, H; Nagamine, R; Kawahara, S; Takeda, S; Kikuchi, Y; Dashnyam, B; Yoshida, T; Kono, T; Sakai, M

    2013-09-01

    With the aim of evaluating the effect of a Mongolian dairy product derived Lactobacillus paracasei spp. paracasei (strain 06TCa22) (Lpp) on the cytokine-mediated immune responses to Vibrio harveyi infection, we examined 16 cytokine expressions in the Japanese pufferfish, Takifugu rubripes. Fish were orally treated with the heat-killed Lpp at 1 mg g(-1) body weight d(-1) for 3 days. At 24 h posttreatment, fish were infected by an intramuscular injection of 0.1 mL V. harveyi bacterial suspension (10(8) cfu mL(-1)). Additionally, superoxide anion production (SAP) and phagocytic activity (PA) of head kidney cells were assessed during 120 h postinfection period. Significant up-regulation of pro-inflammatory (IL-1β, IL-6, IL-17A/F-3, TNF-α and TNF-N), cell-mediated immune inducing (IL-12p35, IL-12p40 and IL-18), antiviral/intra-cellular pathogen killing (I-IFN-1 and IFN-γ), anti-inflammatory (IL-10) and lymphocyte agonistic (IL-2, IL-7, IL-15, IL-21 and TGF-β1) cytokines was observed in the treated fish compared to control ones during the pathogen infection. Furthermore, significantly increased SAP and PA (P < 0.01; 0.05) were recorded in the treated fish compared to untreated fish. These results suggest the beneficial role of Lpp in enhancement of cytokine-mediated immunity in the Japanese pufferfish against V. harveyi infection and application of this product as a potential fish immunostimulant. Copyright © 2013 Elsevier Ltd. All rights reserved.

  3. NF-κB Mediates the Stimulation of Cytokine and Chemokine Expression by Human Articular Chondrocytes in Response to Fibronectin Fragments1

    Science.gov (United States)

    Pulai, Judit I.; Chen, Hong; Im, Hee-Jeong; Kumar, Sanjay; Hanning, Charles; Hegde, Priti S.; Loeser, Richard F.

    2010-01-01

    Fibronectin fragments (FN-f) that bind to the α5β1 integrin stimulate chondrocyte-mediated cartilage destruction and could play an important role in the progression of arthritis. The objective of this study was to identify potential cytokine mediators of cartilage inflammation and destruction induced by FN-f and to investigate the mechanism of their stimulation. Human articular chondrocytes, isolated from normal ankle cartilage obtained from tissue donors, were treated with a 110-kDa FN-f in serum-free culture, and expression of various cytokine genes was analyzed by cDNA microarray and by a cytokine protein array. Compared with untreated control cultures, stimulation by FN-f resulted in a >2-fold increase in IL-6, IL-8, MCP-1, and growth-related oncogene β (GRO-β). Constitutive and FN-f-inducible expression of GRO-α and GRO-γ were also noted by RT-PCR and confirmed by immunoblotting. Previous reports of IL-1β expression induced by FN-f were also confirmed, while TNF expression was found to be very low. Inhibitor studies revealed that FN-f-induced stimulation of chondrocyte chemokine expression was dependent on NF-κB activity, but independent of IL-1 autocrine signaling. The ability of FN-f to stimulate chondrocyte expression of multiple proinflammatory cytokines and chemokines suggests that damage to the cartilage matrix is capable of inducing a proinflammatory state responsible for further progressive matrix destruction, which also includes the chemoattraction of inflammatory cells. Targeting the signaling pathways activated by FN-f may be an effective means of inhibiting production of multiple mediators of cartilage destruction. PMID:15843581

  4. Comparative study of the cytokine/chemokine response in children with differing disease severity in enterovirus 71-induced hand, foot, and mouth disease.

    Directory of Open Access Journals (Sweden)

    Yan Zhang

    Full Text Available BACKGROUND: Enterovirus 71 (EV71 infection can lead to a rapidly progressing, life-threatening, and severe neurological disease in young children, including the development of human hand, foot, and mouth disease (HFMD. This study aims to further characterize the specific immunological features in EV71-mediated HFMD patients presenting with differing degrees of disease severity. METHODOLOGY: Comprehensive cytokine and chemokine expression were broadly evaluated by cytokine antibody array in EV71-infected patients hospitalized for HFMD compared to Coxsackievirus A16-infected patients and age-matched healthy controls. More detailed analysis using Luminex-based cytokine bead array was performed in EV71-infected patients stratified into diverse clinic outcomes. Additionally, immune cell frequencies in peripheral blood and EV71-specific antibodies in plasma were also examined. PRINCIPAL FINDINGS: Expression of several cytokines and chemokines were significantly increased in plasma from EV71-infected patients compared to healthy controls, which further indicated that: (1 GM-CSF, MIP-1β, IL-2, IL-33, and IL-23 secretion was elevated in patients who rapidly developed disease and presented with uncomplicated neurological damage; (2 G-CSF and MCP-1 were distinguishably secreted in EV71 infected very severe patients presenting with acute respiratory failure; (3 IP-10, MCP-1, IL-6, IL-8, and G-CSF levels were much higher in cerebrospinal fluid than in plasma from patients with neurological damage; (4 FACS analysis revealed that the frequency of CD19(+HLADR(+ mature B cells dynamically changed over time during the course of hospitalization and was accompanied by dramatically increased EV71-specific antibodies. Our data provide a panoramic view of specific immune mediator and cellular immune responses of HFMD and may provide useful immunological profiles for monitoring the progress of EV71-induced fatal neurological symptoms with acute respiratory failure.

  5. CR3 and Dectin-1 Collaborate in Macrophage Cytokine Response through Association on Lipid Rafts and Activation of Syk-JNK-AP-1 Pathway.

    Directory of Open Access Journals (Sweden)

    Juin-Hua Huang

    2015-07-01

    Full Text Available Collaboration between heterogeneous pattern recognition receptors (PRRs leading to synergistic coordination of immune response is important for the host to fight against invading pathogens. Although complement receptor 3 (CR3 and Dectin-1 are major PRRs to detect fungi, crosstalk between these two receptors in antifungal immunity is largely undefined. Here we took advantage of Histoplasma capsulatum which is known to interact with both CR3 and Dectin-1 and specific particulate ligands to study the collaboration of CR3 and Dectin-1 in macrophage cytokine response. By employing Micro-Western Array (MWA, genetic approach, and pharmacological inhibitors, we demonstrated that CR3 and Dectin-1 act collaboratively to trigger macrophage TNF and IL-6 response through signaling integration at Syk kinase, allowing subsequent enhanced activation of Syk-JNK-AP-1 pathway. Upon engagement, CR3 and Dectin-1 colocalize and form clusters on lipid raft microdomains which serve as a platform facilitating their cooperation in signaling activation and cytokine production. Furthermore, in vivo studies showed that CR3 and Dectin-1 cooperatively participate in host defense against disseminated histoplasmosis and instruct adaptive immune response. Taken together, our findings define the mechanism of receptor crosstalk between CR3 and Dectin-1 and demonstrate the importance of their collaboration in host defense against fungal infection.

  6. Thermal response of a pin-type fusion reactor blanket during steady and transient reactor operation

    International Nuclear Information System (INIS)

    Grotz, S.; Ghoniem, N.M.

    1986-02-01

    The thermal analysis of the blanket examines both the steady-state and transient reactor operations. The steady-state analysis covers full power and fractional power operation whereas the transient analysis examines the effects of power ramps and blanket preheat. The blanket configuration chosen for this study is a helium cooled solid breeder design. We first discuss the full power, steady-state temperature fields in the first wall, beryllium rods, and breeder rods. Next we examine the effects of fractional power on coolant flow and temperature field distributions. This includes power plateaus of 10%, 20%, 50%, 80%, and 100% of full power. Also examined are the restrictions on the rates of power ramping between plateaus. Finally we discuss the power and time requirements for pre-heating the primary from cold iron conditions up to startup temperature (250 0 C)

  7. Effects of different block size distributions in pressure transient response of naturally fractured reservoirs

    Energy Technology Data Exchange (ETDEWEB)

    Montazeri, G.H. [Islamic Azad University, Mahshahr (Iran, Islamic Republic of). Dept. of Chemical and Petroleum Engineering], E-mail: montazeri_gh@yahoo.com; Tahami, S.A. [Mad Daneshgostar Tabnak Co. (MDT),Tehran (Iran, Islamic Republic of); Moradi, B.; Safari, E. [Iranian Central Oil Fields Co, Tehran (Iran, Islamic Republic of)], E-mail: morady.babak@gmail.com

    2011-07-15

    This paper presents a model for pressure transient and derivative analysis for naturally fractured reservoirs by a formulation of inter porosity flow incorporating variations in matrix block size, which is inversely related to fracture intensity. Geologically realistic Probability Density Functions (PDFs) of matrix block size, such as uniform, bimodal, linear and exponential distributions, are examined and pseudo-steady-state and transient models for inter porosity flow are assumed. The results have been physically interpreted, and, despite results obtained by other authors, it was found that the shape of pressure derivative curves for different PDFs are basically identical within some ranges of block size variability, inter porosity skin, PDFs parameters and matrix storage capacity. This tool can give an insight on the distribution of block sizes and shapes, together with other sources of information such as Logs and geological observations. (author)

  8. Response of centrifugal blowers to simulated tornado transients, July-September 1981

    International Nuclear Information System (INIS)

    Idar, E.S.; Gregory, W.S.; Martin, R.A.; Littleton, P.E.

    1982-03-01

    During this quarter, quasi-steady and dynamic testing of the 24-in. centrifugal blower was completed using the blowdown facility located at New Mexico State University. The data were obtained using a new digital data-acquisition system. Software was developed at the Los Alamos National Laboratory to reduce the dynamic test data and create computer-generated movies showing the dynamic performance of the blower under simulated tornado transient pressure conditions relative to its quasi-steady-state performance. Currently, quadrant-four (outrunning flow) data have been reduced for the most severe and a less severe tornado pressure transient. The results indicate that both the quasi-steady and dynamic blower performance are very similar. Some hysteresis in the dynamic performance occurs because of rotational inertia effects in the blower rotor and drive system. Currently quadrant-two (backflow) data are being transferred to the LTSS computer system at Los Alamos and will be reduced shortly

  9. Transient impedance changes in venous endothelial monolayers as a biological radiation dosimetry response

    Directory of Open Access Journals (Sweden)

    Erik Fossum Young

    2012-10-01

    Full Text Available In March of 2011, a magnitude 9.0 earthquake and subsequent 14 m-high tsunami caused major damage to the Fukushima Daiichi nuclear power plant in Japan.  While cancer incidence in the radiation-exposed population is a logical concern, the complex effects of radiation on the heart and cardiovascular system are also of interest.  Immediate and early vascular radiation effects could be exploited as a dosimetry modality.  To test whether non-coronary vasculature exhibited transient perturbation in barrier function, video microscopy studies and Electric Cell Substrate Impedance Sensing technology were used to probe very subtle changes in primary human vascular endothelium.  Human umbilical vein endothelial cell (HUVEC monolayers exhibit a transient, statistically significant decrease (P = 0.017 in monolayer resistance 3 h after irradiation with 5.0 Gy of g rays.  Radiation induced perturbations in HUVEC monolayer permeability are similar in magnitude and kinetics to those observed in coronary arterial endothelium.  Therefore, at least two types of vasculature respond to radiation on ECIS arrays with an early transient disruption in permeability.  The finding supports the use of early passage HUVECs for use in bioelectric dosimetry studies of vasculature and suggests that permeability of vessels could potentially serve as a biological dosimetry tool.

  10. A fast transient response low dropout regulator with current control methodology

    Energy Technology Data Exchange (ETDEWEB)

    Ma Zhuo; Guo Yang; Duan Zhikui; Xie Lunguo; Chen Jihua; Yu Jinshan, E-mail: guoyang@nudt.edu.cn [School of Computer, National University of Defense Technology, Changsha 410073 (China)

    2011-08-15

    A transient performance optimized CCL-LDO regulator is proposed. In the CCL-LDO, the control method of the charge pump phase-locked loop is adopted. A current control loop has the feedback signal and reference current to be compared, and then a loop filter generates the gate voltage of the power MOSFET by integrating the error current. The CCL-LDO has the optimized damping coefficient and natural resonant frequency, while its output voltage can be sub-1-V and is not restricted by the reference voltage. With a 1 {mu}F decoupling capacitor, the experimental results based on a 0.13 {mu}m CMOS process show that the output voltage is 1.0 V; when the workload changes from 100 {mu}A to 100 mA transiently, the stable dropout is 4.25 mV, the settling time is 8.2 {mu}s and the undershoot is 5.11 mV; when the workload changes from 100 mA to 100 {mu}A transiently, the stable dropout is 4.25 mV, the settling time is 23.3 {mu}s and the overshoot is 6.21 mV. The PSRR value is more than -95 dB. Most of the attributes of the CCL-LDO are improved rapidly with a FOM value of 0.0097.

  11. A fast transient response low dropout regulator with current control methodology

    International Nuclear Information System (INIS)

    Ma Zhuo; Guo Yang; Duan Zhikui; Xie Lunguo; Chen Jihua; Yu Jinshan

    2011-01-01

    A transient performance optimized CCL-LDO regulator is proposed. In the CCL-LDO, the control method of the charge pump phase-locked loop is adopted. A current control loop has the feedback signal and reference current to be compared, and then a loop filter generates the gate voltage of the power MOSFET by integrating the error current. The CCL-LDO has the optimized damping coefficient and natural resonant frequency, while its output voltage can be sub-1-V and is not restricted by the reference voltage. With a 1 μF decoupling capacitor, the experimental results based on a 0.13 μm CMOS process show that the output voltage is 1.0 V; when the workload changes from 100 μA to 100 mA transiently, the stable dropout is 4.25 mV, the settling time is 8.2 μs and the undershoot is 5.11 mV; when the workload changes from 100 mA to 100 μA transiently, the stable dropout is 4.25 mV, the settling time is 23.3 μs and the overshoot is 6.21 mV. The PSRR value is more than -95 dB. Most of the attributes of the CCL-LDO are improved rapidly with a FOM value of 0.0097.

  12. Lactobacillus acidophilus induces a slow but more sustained chemokine and cytokine response in naïve foetal enterocytes compared to commensal Escherichia coli

    Directory of Open Access Journals (Sweden)

    Nellemann Christine

    2010-01-01

    Full Text Available Abstract Background The first exposure to microorganisms at mucosal surfaces is critical for immune maturation and gut health. Facultative anaerobic bacteria are the first to colonise the infant gut, and the impact of these bacteria on intestinal epithelial cells (IEC may be determinant for how the immune system subsequently tolerates gut bacteria. Results To mirror the influence of the very first bacterial stimuli on infant IEC, we isolated IEC from mouse foetuses at gestational day 19 and from germfree neonates. IEC were stimulated with gut-derived bacteria, Gram-negative Escherichia coli Nissle and Gram-positive Lactobacillus acidophilus NCFM, and expression of genes important for immune regulation was measured together with cytokine production. E. coli Nissle and L. acidophilus NCFM strongly induced chemokines and cytokines, but with different kinetics, and only E. coli Nissle induced down-regulation of Toll-like receptor 4 and up-regulation of Toll-like receptor 2. The sensitivity to stimulation was similar before and after birth in germ-free IEC, although Toll-like receptor 2 expression was higher before birth than immediately after. Conclusions In conclusion, IEC isolated before gut colonisation occurs at birth, are highly responsive to stimulation with gut commensals, with L. acidophilus NCFM inducing a slower, but more sustained response than E. coli Nissle. E. coli may induce intestinal tolerance through very rapid up-regulation of chemokine and cytokine genes and down-regulation of Toll-like receptor 4, while regulating also responsiveness to Gram-positive bacteria.

  13. Evidence of Hierarchy in the Complex Fractured System of Geropotamos (Crete, Greece), as Extracted from Transient Electromagnetic Responses

    Science.gov (United States)

    Vallianatos, Filippos; Kouli, Maria; Kalisperi, Despina

    2018-03-01

    The essential goals of this paper are to test the transient electromagnetic (TEM) response in a fractured geological complex medium and to better understand the physics introduced by associating a roughness parameter β to the geological formation. An anomalous fractional diffusion approach is incorporated to describe the electromagnetic induction in rough multi-scaled geological structures. The multi-scaling characteristics of Geropotamos basin in Crete are revealed through the analysis of transient step-off response of an EM loop antenna. The semi-empirical parameters derived from late-time TEM measurements are correlated with the multi-scale heterogeneities of the medium. Certain interesting properties of the late-time slope γ(β) and the power law of near surface resistivity distribution, as extracted from TEM inversion for different depth, are presented. The analysis of the parameter γ(β) which scales the induced voltage in the loop in the late stage of the electromagnetic response leads to a different view of the EM geophysical data interpretation. We show that it is strongly correlated with areas of high fracture density within the geological formations of the Geropotamos area. For that reason, it is proposed as a local multi-scaling empirical index. The results of this paper suggest that anomalous diffusion could be a viable physical mechanism for the fractal transport of charge carriers, explaining observed late-time TEM responses across a variety of natural geological settings.

  14. Unique proliferation response in odontoblastic cells derived from human skeletal muscle stem cells by cytokine-induced matrix metalloproteinase-3

    International Nuclear Information System (INIS)

    Ozeki, Nobuaki; Hase, Naoko; Kawai, Rie; Yamaguchi, Hideyuki; Hiyama, Taiki; Kondo, Ayami; Nakata, Kazuhiko; Mogi, Makio

    2015-01-01

    A pro-inflammatory cytokine mixture (CM: interleukin (IL)-1β, tumor necrosis factor-α and interferon-γ) and IL-1β-induced matrix metalloproteinase (MMP)-3 activity have been shown to increase the proliferation of rat dental pulp cells and murine stem cell-derived odontoblast-like cells. This suggests that MMP-3 may regulate wound healing and regeneration in the odontoblast-rich dental pulp. Here, we determined whether these results can be extrapolated to human dental pulp by investigating the effects of CM-induced MMP-3 up-regulation on the proliferation and apoptosis of purified odontoblast-like cells derived from human skeletal muscle stem cells. We used siRNA to specifically reduce MMP-3 expression. We found that CM treatment increased MMP-3 mRNA and protein levels as well as MMP-3 activity. Cell proliferation was also markedly increased, with no changes in apoptosis, upon treatment with CM and following the application of exogenous MMP-3. Endogenous tissue inhibitors of metalloproteinases were constitutively expressed during all experiments and unaffected by MMP-3. Although treatment with MMP-3 siRNA suppressed cell proliferation, it also unexpectedly increased apoptosis. This siRNA-mediated increase in apoptosis could be reversed by exogenous MMP-3. These results demonstrate that cytokine-induced MMP-3 activity regulates cell proliferation and suppresses apoptosis in human odontoblast-like cells. - Highlights: • Pro-inflammatory cytokines induce MMP-3 activity in human odontoblast-like cells. • Increased MMP-3 activity can promote cell proliferation in odontoblasts. • Specific loss of MMP-3 increases apoptosis in odontoblasts. • MMP-3 has potential as a promising new target for pupal repair and regeneration

  15. Unique proliferation response in odontoblastic cells derived from human skeletal muscle stem cells by cytokine-induced matrix metalloproteinase-3

    Energy Technology Data Exchange (ETDEWEB)

    Ozeki, Nobuaki; Hase, Naoko; Kawai, Rie; Yamaguchi, Hideyuki; Hiyama, Taiki [Department of Endodontics, School of Dentistry, Aichi Gakuin University, 2-11 Suemori-dori, Chikusa-ku, Nagoya 464-8651, Aichi (Japan); Kondo, Ayami [Department of Medicinal Biochemistry, School of Pharmacy, Aichi Gakuin University, 1-100 Kusumoto, Chikusa-ku, Nagoya 464-8650 (Japan); Nakata, Kazuhiko [Department of Endodontics, School of Dentistry, Aichi Gakuin University, 2-11 Suemori-dori, Chikusa-ku, Nagoya 464-8651, Aichi (Japan); Mogi, Makio, E-mail: makio@dpc.agu.ac.jp [Department of Medicinal Biochemistry, School of Pharmacy, Aichi Gakuin University, 1-100 Kusumoto, Chikusa-ku, Nagoya 464-8650 (Japan)

    2015-02-01

    A pro-inflammatory cytokine mixture (CM: interleukin (IL)-1β, tumor necrosis factor-α and interferon-γ) and IL-1β-induced matrix metalloproteinase (MMP)-3 activity have been shown to increase the proliferation of rat dental pulp cells and murine stem cell-derived odontoblast-like cells. This suggests that MMP-3 may regulate wound healing and regeneration in the odontoblast-rich dental pulp. Here, we determined whether these results can be extrapolated to human dental pulp by investigating the effects of CM-induced MMP-3 up-regulation on the proliferation and apoptosis of purified odontoblast-like cells derived from human skeletal muscle stem cells. We used siRNA to specifically reduce MMP-3 expression. We found that CM treatment increased MMP-3 mRNA and protein levels as well as MMP-3 activity. Cell proliferation was also markedly increased, with no changes in apoptosis, upon treatment with CM and following the application of exogenous MMP-3. Endogenous tissue inhibitors of metalloproteinases were constitutively expressed during all experiments and unaffected by MMP-3. Although treatment with MMP-3 siRNA suppressed cell proliferation, it also unexpectedly increased apoptosis. This siRNA-mediated increase in apoptosis could be reversed by exogenous MMP-3. These results demonstrate that cytokine-induced MMP-3 activity regulates cell proliferation and suppresses apoptosis in human odontoblast-like cells. - Highlights: • Pro-inflammatory cytokines induce MMP-3 activity in human odontoblast-like cells. • Increased MMP-3 activity can promote cell proliferation in odontoblasts. • Specific loss of MMP-3 increases apoptosis in odontoblasts. • MMP-3 has potential as a promising new target for pupal repair and regeneration.

  16. TLR4 Gene Expression and Pro-Inflammatory Cytokines in Alzheimer's Disease and in Response to Hippocampal Deafferentation in Rodents.

    Science.gov (United States)

    Miron, Justin; Picard, Cynthia; Frappier, Josée; Dea, Doris; Théroux, Louise; Poirier, Judes

    2018-01-01

    One important aspect in Alzheimer's disease pathology is the presence of chronic inflammation. Considering its role as a key receptor in the microglial innate immune system, TLR4 was shown to regulate the binding and phagocytosis of amyloid plaques by microglia in several mouse models of amyloidosis, as well as the production of pro-inflammatory cytokines. To our knowledge, TLR4 and its association with cytokines have not been thoroughly examined in the brains of subjects affected with Alzheimer's disease. Using quantitative reverse transcription polymerase chain reaction (qRT-PCR) in postmortem human brains, we observed increased expression for the TLR4 and TNF genes (p = 0.001 and p = 0.025, respectively), as well as a trend for higher IL6 gene expression in the frontal cortex of AD subjects when compared to age-matched controls. Similarly, using a mouse model of hippocampal deafferentation without amyloidosis, (i.e., the entorhinal cortex lesioned mouse), we observed significant increases in the expression of both the Tlr4 (p = 0.0367 and p = 0.0193 compared to sham-lesioned mice or to the contralateral side, respectively) and Il1b (p = 0.0055 and p = 0.0066 compared to sham-lesioned mice or to the contralateral side, respectively) genes in the deafferentation phase, but not during the ensuing reinnervation process. In conclusion, we suggest that the modulation of cytokines by TLR4 is differentially regulated whether by the presence of amyloid plaques or by the ongoing deafferentation process.

  17. Application of the Matrix Pencil Method for Estimating the SEM (Singularity Expansion Method) Poles of Source Free Transient Responses From Multiple Look Directions

    National Research Council Canada - National Science Library

    Sarkar, Tapan

    2000-01-01

    .... The SEM poles are independent of the angle at which the transient response is recorded. The only difference between the various waveforms are that the residues at the various poles are of different magnitudes...

  18. Long-term sex-differential effects of neonatal vitamin A supplementation on in vitro cytokine responses

    DEFF Research Database (Denmark)

    Jensen, Kristoffer Jarlov; Søndergaard, Mia J.; Andersen, Andreas

    2017-01-01

    derivative (PPD), tetanus toxoid and lipopolysaccharide. There were no differences between the two doses of NVAS, and thus they were analysed combined as NVAS (any dose) v. placebo. All analyses were performed unstratified and by sex. NVAS increased the chance of having a scar after BCG vaccination...... in females (NVAS v. placebo: 96 v. 71 %, proportion ratio: 1·24; 95 % CI 1·09, 1·42), but not in males (Pfor interaction=0·012). NVAS was associated with significant sex-differential effects on the pro- to anti-inflammatory cytokine ratios (TNF-α:IL-10) to PPD, tetanus toxoid and medium alone, which were...

  19. Divalent metal transporter 1 regulates iron-mediated ROS and pancreatic ß cell fate in response to cytokines

    DEFF Research Database (Denmark)

    Hansen, Jakob Bondo; Tonnesen, Morten Fog; Madsen, Andreas Nygaard

    2012-01-01

    Reactive oxygen species (ROS) contribute to target-cell damage in inflammatory and iron-overload diseases. Little is known about iron transport regulation during inflammatory attack. Through a combination of in vitro and in vivo studies, we show that the proinflammatory cytokine IL-1ß induces...... knockout islets is defective, highlighting a physiological role of iron and ROS in the regulation of insulin secretion. Dmt1 knockout mice are protected against multiple low-dose streptozotocin and high-fat diet-induced glucose intolerance, models of type 1 and type 2 diabetes, respectively. Thus, ß cells...

  20. Brain microvascular pericytes are immunoactive in culture: cytokine, chemokine, nitric oxide, and LRP-1 expression in response to lipopolysaccharide

    Directory of Open Access Journals (Sweden)

    Erickson Michelle A

    2011-10-01

    Full Text Available Abstract Background Brain microvascular pericytes are important constituents of the neurovascular unit. These cells are physically the closest cells to the microvascular endothelial cells in brain capillaries. They significantly contribute to the induction and maintenance of the barrier functions of the blood-brain barrier. However, very little is known about their immune activities or their roles in neuroinflammation. Here, we focused on the immunological profile of brain pericytes in culture in the quiescent and immune-challenged state by studying their production of immune mediators such as nitric oxide (NO, cytokines, and chemokines. We also examined the effects of immune challenge on pericyte expression of low density lipoprotein receptor-related protein-1 (LRP-1, a protein involved in the processing of amyloid precursor protein and the brain-to-blood efflux of amyloid-β peptide. Methods Supernatants were collected from primary cultures of mouse brain pericytes. Release of nitric oxide (NO was measured by the Griess reaction and the level of S-nitrosylation of pericyte proteins measured with a modified "biotin-switch" method. Specific mitogen-activated protein kinase (MAPK pathway inhibitors were used to determine involvement of these pathways on NO production. Cytokines and chemokines were analyzed by multianalyte technology. The expression of both subunits of LRP-1 was analyzed by western blot. Results Lipopolysaccharide (LPS induced release of NO by pericytes in a dose-dependent manner that was mediated through MAPK pathways. Nitrative stress resulted in S-nitrosylation of cellular proteins. Eighteen of twenty-three cytokines measured were released constitutively by pericytes or with stimulation by LPS, including interleukin (IL-12, IL-13, IL-9, IL-10, granulocyte-colony stimulating factor, granulocyte macrophage-colony stimulating factor, eotaxin, chemokine (C-C motif ligand (CCL-3, and CCL-4. Pericyte expressions of both subunits of

  1. Lactococcus lactis carrying a DNA vaccine coding for the ESAT-6 antigen increases IL-17 cytokine secretion and boosts the BCG vaccine immune response.

    Science.gov (United States)

    Pereira, V B; da Cunha, V P; Preisser, T M; Souza, B M; Turk, M Z; De Castro, C P; Azevedo, M S P; Miyoshi, A

    2017-06-01

    A regimen utilizing Bacille Calmette-Guerin (BCG) and another vaccine system as a booster may represent a promising strategy for the development of an efficient tuberculosis vaccine for adults. In a previous work, we confirmed the ability of Lactococcus lactis fibronectin-binding protein A (FnBPA+) (pValac:ESAT-6), a live mucosal DNA vaccine, to produce a specific immune response in mice after oral immunization. In this study, we examined the immunogenicity of this strain as a booster for the BCG vaccine in mice. After immunization, cytokine and immunoglobulin profiles were measured. The BCG prime L. lactis FnBPA+ (pValac:ESAT-6) boost group was the most responsive group, with a significant increase in splenic pro-inflammatory cytokines IL-17, IFN-γ, IL-6 and TNF-α compared with the negative control. Based on the results obtained here, we demonstrated that L. lactis FnBPA+ (pValac:ESAT-6) was able to increase the BCG vaccine general immune response. This work is of great scientific and social importance because it represents the first step towards the development of a booster to the BCG vaccine using L. lactis as a DNA delivery system. © 2017 The Society for Applied Microbiology.

  2. Serum Cytokine Responses over the Entire Clinical-Immunological Spectrum of Human Leishmania (L. infantum chagasi Infection

    Directory of Open Access Journals (Sweden)

    Patrícia Karla Ramos

    2016-01-01

    Full Text Available The clinical-immunological spectrum of human Leishmania (L. infantum chagasi infection in Amazonian Brazil was recently reviewed based on clinical, DTH, and IFAT (IgG evaluations that identified five profiles: three asymptomatic (asymptomatic infection, AI; subclinical resistant infection, SRI; and indeterminate initial infection, III and two symptomatic (symptomatic infection, SI; American visceral leishmaniasis, AVL; and subclinical oligosymptomatic infection, SOI. TNF-α, IL-4, IL-6, and IL-10 serum cytokines were analyzed using multiplexed Cytometric Bead Array in 161 samples from endemic areas in the Brazilian Amazon: SI [AVL] (21 cases, III (49, SRI (19, SOI (12, AI (36, and a control group [CG] (24. The highest IL-6 serum levels were observed in the SI profile (AVL; higher IL-10 serum levels were observed in SI than in SOI or CG and in AI and III than in SOI; higher TNF-α serum levels were seen in SI than in CG. Positive correlations were found between IL-6 and IL-10 serum levels in the SI and III profiles and between IL-6 and TNF-α and between IL-4 and TNF-α in the III profile. These results provide strong evidence for associating IL-6 and IL-10 with the immunopathogenesis of AVL and help clarify the role of these cytokines in the infection spectrum.

  3. Parecoxib is neuroprotective in spontaneously hypertensive rats after transient middle cerebral artery occlusion: a divided treatment response?

    Science.gov (United States)

    Kelsen, Jesper; Kjaer, Katrine; Chen, Gang; Pedersen, Michael; Røhl, Lisbeth; Frøkiaer, Jørgen; Nielsen, Søren; Nyengaard, Jens R; Rønn, Lars Christian B

    2006-12-06

    Anti-inflammatory treatment affects ischemic damage and neurogenesis in rodent models of cerebral ischemia. We investigated the potential benefit of COX-2 inhibition with parecoxib in spontaneously hypertensive rats (SHRs) subjected to transient middle cerebral artery occlusion (tMCAo). Sixty-four male SHRs were randomized to 90 min of intraluminal tMCAo or sham surgery. Parecoxib (10 mg/kg) or isotonic saline was administered intraperitoneally (IP) during the procedure, and twice daily thereafter. Nineteen animals were euthanized after 24 hours, and each hemisphere was examined for mRNA expression of pro-inflammatory cytokines and COX enzymes by quantitative RT-PCR. Twenty-three tMCAo animals were studied with diffusion and T2 weighted MRI within the first 24 hours, and ten of the SHRs underwent follow-up MRI six days later. Thirty-three SHRs were given 5-bromo-2'-deoxy-uridine (BrdU) twice daily on Day 4 to 7 after tMCAo. Animals were euthanized on Day 8 and the brains were studied with free-floating immunohistochemistry for activated microglia (ED-1), hippocampal granule cell BrdU incorporation, and neuronal nuclei (NeuN). Infarct volume estimation was done using the 2D nucleator and Cavalieri principle on NeuN-stained coronal brain sections. The total number of BrdU+ cells in the dentate gyrus (DG) of the hippocampus was estimated using the optical fractionator. We found a significant reduction in infarct volume in parecoxib treated animals one week after tMCAo (p < 0.03). Cortical ADC values in the parecoxib group were markedly less increased on Day 8 (p < 0.01). Interestingly, the parecoxib treated rats were segregated into two subgroups, suggesting a responder vs. non-responder phenomenon. We found indications of mRNA up-regulation of IL-1beta, IL-6, TNF-alpha and COX-2, whereas COX-1 remained unaffected. Hippocampal granule cell BrdU incorporation was not affected by parecoxib treatment. Presence of ED-1+ activated microglia in the hippocampus was related

  4. SPICE modelling of the transient response of irradiated MOSFETs; Modelisation de la reponse transitoire de MOSFETs irradies avec SPICE

    Energy Technology Data Exchange (ETDEWEB)

    Pouget, V.; Lapuyade, H.; Lewis, D.; Deval, Y.; Fouillat, P. [Bordeaux-1 Univ., IXL, 33 - Talence (France); Sarger, L. [Bordeaux-1 Univ., CPMOH, 33 - Talence (France)

    1999-07-01

    A new SPICE model of irradiated MOSFET taking into account the real response of the 4 electrodes is proposed. The component that has been simulated is an NMOS transistor issued from the AMS BiCMOS 0.8 {mu}m technology. A comparison between SPICE-generated transients and PISCES device simulation demonstrates the accuracy benefits when used in complex electronic architectures. This model could be used when designing electronic circuits able to sustain hardening due to SEE (single event effect), it will be an efficient complement to the physical simulations.

  5. Effect of burnup on the response of stainless steel-clad mixed-oxide fuels to simulated thermal transients

    International Nuclear Information System (INIS)

    Fenske, G.R.; Badyopadhyay, G.

    1981-01-01

    Direct electrical heating experiments were performed on irradiated fuel to study the fuel and cladding response as a function of burnup during a slow thermal transient. The results indicated that the nature and extent of the fuel and cladding behavior depended on the quantity of fission gas retained in the fuel. Fission-gas-driven fuel ejection occurred as the molten cladding flowed down the stack exposing bare, radially unrestrained fuel. The fuel dispersion occurred in the absence of molten fuel and the amount of fuel ejected increased with increasing burnup. 31 refs

  6. Neonatal plasma polarizes TLR4-mediated cytokine responses towards low IL-12p70 and high IL-10 production via distinct factors.

    Directory of Open Access Journals (Sweden)

    Mirjam E Belderbos

    Full Text Available Human neonates are highly susceptible to infection, which may be due in part to impaired innate immune function. Neonatal Toll-like receptor (TLR responses are biased against the generation of pro-inflammatory/Th1-polarizing cytokines, yet the underlying mechanisms are incompletely defined. Here, we demonstrate that neonatal plasma polarizes TLR4-mediated cytokine production. When exposed to cord blood plasma, mononuclear cells (MCs produced significantly lower TLR4-mediated IL-12p70 and higher IL-10 compared to MC exposed to adult plasma. Suppression by neonatal plasma of TLR4-mediated IL-12p70 production, but not induction of TLR4-mediated IL-10 production, was maintained up to the age of 1 month. Cord blood plasma conferred a similar pattern of MC cytokine responses to TLR3 and TLR8 agonists, demonstrating activity towards both MyD88-dependent and MyD88-independent agonists. The factor causing increased TLR4-mediated IL-10 production by cord blood plasma was heat-labile, lost after protein depletion and independent of lipoprotein binding protein (LBP or soluble CD14 (sCD14. The factor causing inhibition of TLR4-mediated IL-12p70 production by cord blood plasma was resistant to heat inactivation or protein depletion and was independent of IL-10, vitamin D and prostaglandin E2. In conclusion, human neonatal plasma contains at least two distinct factors that suppress TLR4-mediated IL-12p70 production or induce IL-10 or production. Further identification of these factors will provide insight into the ontogeny of innate immune development and might identify novel targets for the prevention and treatment of neonatal infection.

  7. Neonatal Plasma Polarizes TLR4-Mediated Cytokine Responses towards Low IL-12p70 and High IL-10 Production via Distinct Factors

    Science.gov (United States)

    Belderbos, Mirjam E.; Levy, Ofer; Stalpers, Femke; Kimpen, Jan L.; Meyaard, Linde; Bont, Louis

    2012-01-01

    Human neonates are highly susceptible to infection, which may be due in part to impaired innate immune function. Neonatal Toll-like receptor (TLR) responses are biased against the generation of pro-inflammatory/Th1-polarizing cytokines, yet the underlying mechanisms are incompletely defined. Here, we demonstrate that neonatal plasma polarizes TLR4-mediated cytokine production. When exposed to cord blood plasma, mononuclear cells (MCs) produced significantly lower TLR4-mediated IL-12p70 and higher IL-10 compared to MC exposed to adult plasma. Suppression by neonatal plasma of TLR4-mediated IL-12p70 production, but not induction of TLR4-mediated IL-10 production, was maintained up to the age of 1 month. Cord blood plasma conferred a similar pattern of MC cytokine responses to TLR3 and TLR8 agonists, demonstrating activity towards both MyD88-dependent and MyD88-independent agonists. The factor causing increased TLR4-mediated IL-10 production by cord blood plasma was heat-labile, lost after protein depletion and independent of lipoprotein binding protein (LBP) or soluble CD14 (sCD14). The factor causing inhibition of TLR4-mediated IL-12p70 production by cord blood plasma was resistant to heat inactivation or protein depletion and was independent of IL-10, vitamin D and prostaglandin E2. In conclusion, human neonatal plasma contains at least two distinct factors that suppress TLR4-mediated IL-12p70 production or induce IL-10 or production. Further identification of these factors will provide insight into the ontogeny of innate immune development and might identify novel targets for the prevention and treatment of neonatal infection. PMID:22442690

  8. Generalized Liver- and Blood-Derived CD8+ T-Cell Impairment in Response to Cytokines in Chronic Hepatitis C Virus Infection.

    Directory of Open Access Journals (Sweden)

    Stephanie C Burke Schinkel

    Full Text Available Generalized CD8+ T-cell impairment in chronic hepatitis C virus (HCV infection and the contribution of liver-infiltrating CD8+ T-cells to the immunopathogenesis of this infection remain poorly understood. It is hypothesized that this impairment is partially due to reduced CD8+ T-cell activity in response to cytokines such as IL-7, particularly within the liver. To investigate this, the phenotype and cytokine responsiveness of blood- and liver-derived CD8+ T-cells from healthy controls and individuals with HCV infection were compared. In blood, IL-7 receptor α (CD127 expression on bulk CD8+ T-cells in HCV infection was no different than controls yet was lower on central memory T-cells, and there were fewer naïve cells. IL-7-induced signalling through phosphorylated STAT5 was lower in HCV infection than in controls, and differed between CD8+ T-cell subsets. Production of Bcl-2 following IL-7 stimulation was also lower in HCV infection and inversely related to the degree of liver fibrosis. In liver-derived CD8+ T-cells, STAT5 activation could not be increased with cytokine stimulation and basal Bcl-2 levels of liver-derived CD8+ T-cells were lower than blood-derived counterparts in HCV infection. Therefore, generalized CD8+ T-cell impairment in HCV infection is characterized, in part, by impaired IL-7-mediated signalling and survival, independent of CD127 expression. This impairment is more pronounced in the liver and may be associated with an increased potential for apoptosis. This generalized CD8+ T-cell impairment represents an important immune dysfunction in chronic HCV infection that may alter patient health.

  9. CFORM- LINEAR CONTROL SYSTEM DESIGN AND ANALYSIS: CLOSED FORM SOLUTION AND TRANSIENT RESPONSE OF THE LINEAR DIFFERENTIAL EQUATION

    Science.gov (United States)

    Jamison, J. W.

    1994-01-01

    CFORM was developed by the Kennedy Space Center Robotics Lab to assist in linear control system design and analysis using closed form and transient response mechanisms. The program computes the closed form solution and transient response of a linear (constant coefficient) differential equation. CFORM allows a choice of three input functions: the Unit Step (a unit change in displacement); the Ramp function (step velocity); and the Parabolic function (step acceleration). It is only accurate in cases where the differential equation has distinct roots, and does not handle the case for roots at the origin (s=0). Initial conditions must be zero. Differential equations may be input to CFORM in two forms - polynomial and product of factors. In some linear control analyses, it may be more appropriate to use a related program, Linear Control System Design and Analysis (KSC-11376), which uses root locus and frequency response methods. CFORM was written in VAX FORTRAN for a VAX 11/780 under VAX VMS 4.7. It has a central memory requirement of 30K. CFORM was developed in 1987.

  10. Transient response in granular quasi-two-dimensional bounded heap flow.

    Science.gov (United States)

    Xiao, Hongyi; Ottino, Julio M; Lueptow, Richard M; Umbanhowar, Paul B

    2017-10-01

    We study the transition between steady flows of noncohesive granular materials in quasi-two-dimensional bounded heaps by suddenly changing the feed rate. In both experiments and simulations, the primary feature of the transition is a wedge of flowing particles that propagates downstream over the rising free surface with a wedge front velocity inversely proportional to the square root of time. An additional longer duration transient process continues after the wedge front reaches the downstream wall. The entire transition is well modeled as a moving boundary problem with a diffusionlike equation derived from local mass balance and a local relation between the flux and the surface slope.

  11. Endogenous brain IL-1 mediates LPS-induced anorexia and hypothalamic cytokine expression.

    Science.gov (United States)

    Layé, S; Gheusi, G; Cremona, S; Combe, C; Kelley, K; Dantzer, R; Parnet, P

    2000-07-01

    The present study was designed to determine the role of endogenous brain interleukin (IL)-1 in the anorexic response to lipopolysaccharide (LPS). Intraperitoneal administration of LPS (5-10 microgram/mouse) induced a dramatic, but transient, decrease in food intake, associated with an enhanced expression of proinflammatory cytokine mRNA (IL-1beta, IL-6, and tumor necrosis factor-alpha) in the hypothalamus. This dose of LPS also increased plasma levels of IL-1beta. Intracerebroventricular pretreatment with IL-1 receptor antagonist (4 microgram/mouse) attenuated LPS-induced depression of food intake and totally blocked the LPS-induced enhanced expression of proinflammatory cytokine mRNA measured in the hypothalamus 1 h after treatment. In contrast, LPS-induced increases in plasma levels of IL-1beta were not altered. These findings indicate that endogenous brain IL-1 plays a pivotal role in the development of the hypothalamic cytokine response to a systemic inflammatory stimulus.

  12. Simulation of Transient Response of Ir-TES for Position-Sensitive TES with Waveform Domain Multiplexing

    Science.gov (United States)

    Minamikawa, Y.; Sato, H.; Mori, F.; Damayanthi, R. M. T.; Takahashi, H.; Ohno, M.

    2008-04-01

    We are developing a new x-ray microcalorimeter based on a superconducting transition edge sensor (TES) as an imaging sensor. Our measurement shows unique waveforms which we consider as an expression of thermal nonuniformity of TES films. This arises from the different thermal responses, so that response signal shapes would vary according to the position of the incident x-ray. This position dependency deteriorate the measured energy resolution, but with appropriate waveform analysis, this would be useful for imaging device. For more inspection, we have developed a simulation code which enables a dynamic simulation to obtain a transient response of the TES by finite differential method. Temperature and electric current distributions are calculated. As a result, we successfully obtained waveform signals. The calculated signal waveforms have similar characteristics to the measured signals. This simulation visualized the transition state of the device and will help to design better detector.

  13. Immune response against the irradiated Bothropstoxin-1 with 60Co: identification of main cytokines involved and the participation of scavengers substances

    International Nuclear Information System (INIS)

    Alves, Janaina Baptista

    2009-01-01

    Considering the effects of gamma radiation on proteins and the ability of immune system to recognize modified macromolecules, we have identified the major cytokines involved in immune response of B10.PL, BALB/c and Knockout- IFNγ mice exposed to native or irradiated bothropstoxin-1 (BTHX-1), in the presence and absence of scavengers substances. In order to evaluate possible molecule structural modifications after being irradiated ( 60 Co gamma rays), bothropstoxin-1 was submitted to SDS-PAGE analyses. Our results indicated that irradiation process has promoted modifications in the BTHX-1 molecule, however, in the presence of scavengers and even after irradiation process, the main band of toxin was preserved (14 kDa). Sera of animals immunized with the native or irradiated toxin, in the presence or not of scavengers, were analyzed in order to quantify specific isotopes. While the native BTHX-1 induced a predominant Th2 response, the irradiated toxin apparently promoted a switch towards a Th1 pattern. The toxin, when irradiated in the presence of t-butanol, induced to a lower production of IgG2b (Th1 response) if compared with the irradiated toxin without scavengers. We also performed a Real-time PCR to quantify the expression of cytokines IFN-γ, IL-2, IL-4 and IL-10 in spleen cells from mice. The cells of B10.PL and BALB/c mice immunized with native BTHX-1 and in vitro stimulated with irradiated toxin, showed higher expression of IFN-γ and IL-2 (Th1 response) than the control sample. The cells of Knockout-IFNγ mice immunized with native BTHX-1 showed higher expression of IL-4 (Th2 response). The cells obtained of B10.PL and BALB/c mice immunized with BTHX-1 + t-butanol, showed higher expression of IL-4 and IL-10, respectively. These facts reinforce the involvement of OH in the modulation of immune response against the irradiated toxin. (author)

  14. Leucocytes, cytokines and satellite cells

    DEFF Research Database (Denmark)

    Paulsen, Gøran; Mikkelsen, Ulla Ramer; Raastad, Truls

    2012-01-01

    uncertain. The COX enzymes regulate satellite cell activity, as demonstrated in animal models; however the roles of the COX enzymes in human skeletal muscle need further investigation. We suggest using the term 'muscle damage' with care. Comparisons between studies and individuals must consider changes......-damaging exercise', primarily eccentric exercise. We review the evidence for the notion that the degree of muscle damage is related to the magnitude of the cytokine response. In the third and final section, we look at the satellite cell response to a single bout of eccentric exercise, as well as the role...... variation in individual responses to a given exercise should, however be expected. The link between cytokine and satellite cell responses and exercise-induced muscle damage is not so clear The systemic cytokine response may be linked more closely to the metabolic demands of exercise rather than muscle...

  15. Cytokine production but lack of proliferation in peripheral blood mononuclear cells from chronic Chagas' disease cardiomyopathy patients in response to T. cruzi ribosomal P proteins.

    Directory of Open Access Journals (Sweden)

    Silvia A Longhi

    2014-06-01

    Full Text Available BACKGROUND: Trypanosoma cruzi ribosomal P proteins, P2β and P0, induce high levels of antibodies in patients with chronic Chagas' disease Cardiomyopathy (CCC. It is well known that these antibodies alter the beating rate of cardiomyocytes and provoke apoptosis by their interaction with β1-adrenergic and M2-muscarinic cardiac receptors. Based on these findings, we decided to study the cellular immune response to these proteins in CCC patients compared to non-infected individuals. METHODOLOGY/PRINCIPAL FINDINGS: We evaluated proliferation, presence of surface activation markers and cytokine production in peripheral blood mononuclear cells (PBMC stimulated with P2β, the C-terminal portion of P0 (CP0 proteins and T. cruzi lysate from CCC patients predominantly infected with TcVI lineage. PBMC from CCC patients cultured with P2β or CP0 proteins, failed to proliferate and express CD25 and HLA-DR on T cell populations. However, multiplex cytokine assays showed that these antigens triggered higher secretion of IL-10, TNF-α and GM-CSF by PBMC as well as both CD4+ and CD8+ T cells subsets of CCC subjects. Upon T. cruzi lysate stimulation, PBMC from CCC patients not only proliferated but also became activated within the context of Th1 response. Interestingly, T. cruzi lysate was also able to induce the secretion of GM-CSF by CD4+ or CD8+ T cells. CONCLUSIONS/SIGNIFICANCE: Our results showed that although the lack of PBMC proliferation in CCC patients in response to ribosomal P proteins, the detection of IL-10, TNF-α and GM-CSF suggests that specific T cells could have both immunoregulatory and pro-inflammatory potential, which might modulate the immune response in Chagas' disease. Furthermore, it was possible to demonstrate for the first time that GM-CSF was produced by PBMC of CCC patients in response not only to recombinant ribosomal P proteins but also to parasite lysate, suggesting the value of this cytokine to evaluate T cells responses in T

  16. Anti-inflammatory effects of the new generation synthetic surfactant CHF5633 on Ureaplasma-induced cytokine responses in human monocytes.

    Science.gov (United States)

    Glaser, Kirsten; Fehrholz, Markus; Henrich, Birgit; Claus, Heike; Papsdorf, Michael; Speer, Christian P

    2017-02-01

    Synthetic surfactants represent a promising alternative to animal-derived preparations in the treatment of neonatal respiratory distress syndrome. The synthetic surfactant CHF5633 has proven biophysical effectiveness and, moreover, demonstrated anti-inflammatory effects in LPS-stimulated monocytes. With ureaplasmas being relevant pathogens in preterm lung inflammation, the present study addressed immunomodulatory features on Ureaplasma-induced monocyte cytokine responses. Ureaplasma parvum-stimulated monocytes were exposed to CHF5633. TNF-α, IL-1β, IL-8, IL-10, TLR2 and TLR4 expression were analyzed using qPCR and flow cytometry. CHF5633 did not induce pro-inflammation, and did not aggravate Ureaplasma-induced pro-inflammatory cytokine responses. It suppressed U. parvum-induced intracellular TNF-α (p Ureaplasma-induced TNF-α mRNA (p Ureaplasma-modulated IL-8, IL-10, TLR2 and TLR4 were unaffected. CHF5633 does neither act pro-apoptotic nor pro-inflammatory in native and Ureaplasma-infected monocytes. Suppression of Ureaplasma-induced TNF-α and IL-1β underlines anti-inflammatory features of CHF5633.

  17. Regulation of cytokine production in human alveolar macrophages and airway epithelial cells in response to ambient air pollution particles: Further mechanistic studies

    International Nuclear Information System (INIS)

    Becker, Susanne; Mundandhara, Sailaja; Devlin, Robert B.; Madden, Michael

    2005-01-01

    In order to better understand how ambient air particulate matter (PM) affect lung health, the two main airway cell types likely to interact with inhaled particles, alveolar macrophages (AM) and airway epithelial cells have been exposed to particles in vitro and followed for endpoints of inflammation, and oxidant stress. Separation of Chapel Hill PM 10 into fine and coarse size particles revealed that the main proinflammatory response (TNF, IL-6, COX-2) in AM was driven by material present in the coarse PM, containing 90-95% of the stimulatory material in PM10. The particles did not affect expression of hemoxygenase-1 (HO-1), a sensitive marker of oxidant stress. Primary cultures of normal human bronchial epithelial cells (NHBE) also responded to the coarse fraction with higher levels of IL-8 and COX-2, than induced by fine or ultrafine PM. All size PM induced oxidant stress in NHBE, while fine PM induced the highest levels of HO-1 expression. The production of cytokines in AM by both coarse and fine particles was blocked by the toll like receptor 4 (TLR4) antagonist E5531 involved in the recognition of LPS and Gram negative bacteria. The NHBE were found to recognize coarse and fine PM through TLR2, a receptor with preference for recognition of Gram positive bacteria. Compared to ambient PM, diesel PM induced only a minimal cytokine response in both AM and NHBE. Instead, diesel suppressed LPS-induced TNF and IL-8 release in AM. Both coarse and fine ambient air PM were also found to inhibit LPS-induced TNF release while silica, volcanic ash or carbon black had no inhibitory effect. Diesel particles did not affect cytokine mRNA induction nor protein accumulation but interfered with the release of cytokine from the cells. Ambient coarse and fine PM, on the other hand, inhibited both mRNA induction and protein production. Exposure to coarse and fine PM decreased the expression of TLR4 in the macrophages. Particle-induced decrease in TLR4 and hyporesponsiveness to LPS

  18. Fuel rod response to BWR power oscillations during anticipated transient without scram

    International Nuclear Information System (INIS)

    Cunningham, M.; Scott, H.

    1998-01-01

    The US NRC is examining fuel behaviour during a postulated BWR anticipated transient without scram (ATWS) with power oscillations to determine if current regulatory criteria are adequate. Currently, the 280 cal/g limit for RIAs is used to show that coolable geometry is maintained and pressure pulses are avoided during ATWSs. Two specific questions have now been raised about the continued use of the 280 cal/g value. First, this value was derived from energy deposition values whereas the regulatory requirements are written in terms of fuel enthalpy. The second is that fuel rod rupture with fuel dispersal has been observed in RIA tests with high bum-up fuel rods having energy deposition values well below the current limit. However, the BWR ATWS power oscillation transient is slower than a RIA power pulse, thus reducing the likelihood of failure. Therefore questions about the adequacy of the 280 cal/g limit do not necessarily imply unacceptable fuel damage occurring during such power oscillations and there is no immediate safety concern. The reported analysis, using the FRAPTRAN transient fuel rod analysis code, was thus undertaken to determine if further investigation might be appropriate and with the intention of starting some discussions about the issue. There was a comment that a limit of 100 cal/g fuel enthalpy had been mentioned following the scoping calculations but that perhaps enthalpy was not the main concern in an ATWS. It was also observed that cladding stresses are lower than in all RIA. The question was what really is the main concern. It was replied that the main concern was a question of maintaining a coolable geometry i.e. not loosing fuel particles out of the rod. And it was agreed that enthalpy may not be the important issue, rather that it previously had been used as the parameter and so had been considered. Confirmation of this presently being an evaluation and not a regulatory concern was sought and provided, it being pointed out that the NRC

  19. Mimicking mechanical response of natural tissues. Strain hardening induced by transient reticulation in lactose-modified chitosan (chitlac).

    Science.gov (United States)

    Cok, Michela; Sacco, Pasquale; Porrelli, Davide; Travan, Andrea; Borgogna, Massimiliano; Marsich, Eleonora; Paoletti, Sergio; Donati, Ivan

    2018-01-01

    The effect of transient cross-links has been explored on a lactose-modified chitosan, which previously had shown interesting biological features. The presence of galactose side chains and of the polyol spacer resulted particularly appealing for the reticulation by borate ions. The interaction between chitlac and borax was investigated by means of 11 B NMR while rheology pointed to a marked non-linear behavior depending on the amount of borax added to the system. The presence of limited amount of cross-linking ion led to dilatant behavior when the steady flow curve was measured. In addition, strain stiffening was noticed on elastic response upon exceeding a critical stress, indicating a transient nature in the formation of the cross-links. The non-linear response of chitlac in the presence of borax compared surprisingly well with the one showed by proteins composing the natural ECM pointing at a possible role of mechanotransduction in the biological significance of the modified chitosan. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. The impact of transient combination antiretroviral treatment in early HIV infection on viral suppression and immunologic response in later treatment.

    Science.gov (United States)

    Pantazis, Nikos; Touloumi, Giota; Meyer, Laurence; Olson, Ashley; Costagliola, Dominique; Kelleher, Anthony D; Lutsar, Irja; Chaix, Marie-Laure; Fisher, Martin; Moreno, Santiago; Porter, Kholoud

    2016-03-27

    Effects of transient combination antiretroviral treatment (cART) initiated during early HIV infection (EHI) remain unclear. We investigate whether this intervention affects viral suppression and CD4 cell count increase following its reinitiation in chronic infection (CHI). Longitudinal observational study. We identified adult patients from Concerted Action of Seroconversion to AIDS and Death in Europe who seroconverted after 1/1/2000, had a 12 months or less HIV test interval and initiated cART from naive. We classified individuals as 'pretreated in EHI' if treated within 6 months of seroconversion, interrupted for at least 12 weeks, and reinitiated during CHI. Statistical analysis was performed using survival analysis methods and mixed models. Pretreated and initiated in CHI groups comprised 202 and 4263 individuals, with median follow-up after CHI treatment 4.5 and 3 years, respectively. Both groups had similar virologic response and relapse rates (P = 0.585 and P = 0.206) but pretreated individuals restarted treatment with higher baseline CD4 cell count (∼80 cells/μl; P treatment (re)initiation. Assuming common baseline CD4 cell count, differences in CD4 cell count slopes were nonsignificant. Immunovirologic response to CHI treatment was not associated with timing or duration of the transient treatment. Although treatment interruptions are not recommended, stopping cART initiated in EHI does not seem to reduce the chance of a successful outcome of treatment in CHI.

  1. No evidence of harms of probiotic Lactobacillus rhamnosus GG ATCC 53103 in healthy elderly-a phase I open label study to assess safety, tolerability and cytokine responses.

    Directory of Open Access Journals (Sweden)

    Patricia L Hibberd

    Full Text Available Although Lactobacillus rhamnosus GG ATCC 53103 (LGG has been consumed by 2 to 5 million people daily since the mid 1990s, there are few clinical trials describing potential harms of LGG, particularly in the elderly.The primary objective of this open label clinical trial is to assess the safety and tolerability of 1×1010 colony forming units (CFU of LGG administered orally twice daily to elderly volunteers for 28 days. The secondary objectives were to evaluate the effects of LGG on the gastrointestinal microbiome, host immune response and plasma cytokines.Fifteen elderly volunteers, aged 66-80 years received LGG capsules containing 1×1010 CFU, twice daily for 28 days and were followed through day 56. Volunteers completed a daily diary, a telephone call on study days 3, 7 and 14 and study visits in the Clinical Research Center at baseline, day 28 and day 56 to determine whether adverse events had occurred. Assessments included prompted and open-ended questions.There were no serious adverse events. The 15 volunteers had a total of 47 events (range 1-7 per volunteer, 39 (83% of which were rated as mild and 40% of which were considered related to consuming LGG. Thirty-one (70% of the events were expected, prompted symptoms while 16 were unexpected events. The most common adverse events were gastrointestinal (bloating, gas, and nausea, 27 rated as mild and 3 rated as moderate. In the exploratory analysis, the pro-inflammatory cytokine interleukin 8 decreased during LGG consumption, returning towards baseline one month after discontinuing LGG (p = 0.038 while there was no difference in other pro- or anti-inflammatory plasma cytokines.Lactobacillus rhamnosus GG ATCC 53103 is safe and well tolerated in healthy adults aged 65 years and older.ClinicalTrials.gov NCT 01274598.

  2. [EFFECT OF 4-METHYLPYRAZOLE ON IMMUNE RESPONSE, FUNCTION OF Th1 AND Th2 LYMPHOCYTES, AND CYTOKINE CONCENTRATION IN RAT BLOOD AFTER ACUTE METHANOL POISONING].

    Science.gov (United States)

    Zabrodskii, P F; Maslyakov, V V; Gromov, M S

    2016-01-01

    It was established in experiments on noninbred albino rats that the acute intoxication with methanol (1.0 LD50) decreased cellular and humoral immune responses, Th2-lymphocyte activity (to a greater extent as compared to the function of Th1 cells), reduced the blood concentration of immunoregulatory (IFN-g, IL-2, IL-4) and proinflammatory (TNF, IL-1b, IL-6) cytokines on the average by 36.5% (p Methanol antidote 4-methylpyrazole (non-competitive inhibitor of alcohol dehydrogenase) administered upon acute intoxication with methanol at a dose of 1.0 DL50 partially reduces the intoxication-induced suppression of humoral and cellular immune response, activity of T-helper cells, and production of IL-4 and restores blood levels of TNF, IL-1b, IFN-γ, IL-4, IL-2, IL-6 to the control values.

  3. A 2D Daubechies finite wavelet domain method for transient wave response analysis in shear deformable laminated composite plates

    Science.gov (United States)

    Nastos, C. V.; Theodosiou, T. C.; Rekatsinas, C. S.; Saravanos, D. A.

    2018-03-01

    An efficient numerical method is developed for the simulation of dynamic response and the prediction of the wave propagation in composite plate structures. The method is termed finite wavelet domain method and takes advantage of the outstanding properties of compactly supported 2D Daubechies wavelet scaling functions for the spatial interpolation of displacements in a finite domain of a plate structure. The development of the 2D wavelet element, based on the first order shear deformation laminated plate theory is described and equivalent stiffness, mass matrices and force vectors are calculated and synthesized in the wavelet domain. The transient response is predicted using the explicit central difference time integration scheme. Numerical results for the simulation of wave propagation in isotropic, quasi-isotropic and cross-ply laminated plates are presented and demonstrate the high spatial convergence and problem size reduction obtained by the present method.

  4. Assessing the implications of human land-use change for the transient climate response to cumulative carbon emissions

    International Nuclear Information System (INIS)

    Simmons, C T; Matthews, H D

    2016-01-01

    Recent research has shown evidence of a linear climate response to cumulative CO 2 emissions, which implies that the source, timing, and amount of emissions does not significantly influence the climate response per unit emission. Furthermore, these analyses have generally assumed that the climate response to land-use CO 2 emissions is equivalent to that of fossil fuels under the assumption that, once in the atmosphere, the radiative forcing induced by CO 2 is not sensitive to the emissions source. However, land-cover change also affects surface albedo and the strength of terrestrial carbon sinks, both of which have an additional climate effect. In this study, we use a coupled climate-carbon cycle model to assess the climate response to historical and future cumulative land-use CO 2 emissions, in order to compare it to the response to fossil fuel CO 2 . We find that when we isolate the CO 2 -induced (biogeochemical) temperature changes associated with land-use change, then the climate response to cumulative land-use emissions is equivalent to that of fossil fuel CO 2 . We show further that the globally-averaged albedo-induced biophysical cooling from land-use change is non-negligible and may be of comparable magnitude to the biogeochemical warming, with the result that the net climate response to land-use change is substantially different from a linear response to cumulative emissions. However, our new simulations suggest that the biophysical cooling from land-use change follows its own independent (negative) linear response to cumulative net land-use CO 2 emissions, which may provide a useful scaling factor for certain applications when evaluating the full transient climate response to emissions. (letter)

  5. Suppressor of cytokine signaling (SOCS genes are silenced by DNA hypermethylation and histone deacetylation and regulate response to radiotherapy in cervical cancer cells.

    Directory of Open Access Journals (Sweden)

    Moon-Hong Kim

    Full Text Available Suppressor of cytokine signaling (SOCS family is an important negative regulator of cytokine signaling and deregulation of SOCS has been involved in many types of cancer. All cervical cancer cell lines tested showed lower expression of SOCS1, SOCS3, and SOCS5 than normal tissue or cell lines. The immunohistochemistry result for SOCS proteins in human cervical tissue also confirmed that normal tissue expressed higher level of SOCS proteins than neighboring tumor. Similar to the regulation of SOCS in other types of cancer, DNA methylation contributed to SOCS1 downregulation in CaSki, ME-180, and HeLa cells. However, the expression of SOCS3 or SOCS5 was not recovered by the inhibition of DNA methylation. Histone deacetylation may be another regulatory mechanism involved in SOCS1 and SOCS3 expression, however, SOCS5 expression was neither affected by DNA methylation nor histone deacetylation. Ectopic expression of SOCS1 or SOCS3 conferred radioresistance to HeLa cells, which implied SOCS signaling regulates the response to radiation in cervical cancer. In this study, we have shown that SOCS expression repressed by, in part, epigenetically and altered SOCS1 and SOCS3 expression could contribute to the radiosensitive phenotype in cervical cancer.

  6. Motavizumab, A Neutralizing Anti-Respiratory Syncytial Virus (Rsv Monoclonal Antibody Significantly Modifies The Local And Systemic Cytokine Responses Induced By Rsv In The Mouse Model

    Directory of Open Access Journals (Sweden)

    Jafri Hasan S

    2007-10-01

    Full Text Available Abstract Motavizumab (MEDI-524 is a monoclonal antibody with enhanced neutralizing activity against RSV. In mice, motavizumab suppressed RSV replication which resulted in significant reduction of clinical parameters of disease severity. We evaluated the effect of motavizumab on the local and systemic immune response induced by RSV in the mouse model. Balb/c mice were intranasally inoculated with 106.5 PFU RSV A2 or medium. Motavizumab was given once intraperitoneally (1.25 mg/mouse as prophylaxis, 24 h before virus inoculation. Bronchoalveolar lavage (BAL and serum samples were obtained at days 1, 5 (acute and 28 (long-term post inoculation and analyzed with a multiplex assay (Beadlyte Upstate, NY for simultaneous quantitation of 18 cytokines: IL-1α, IL-1β, IL-2, IL-3, IL-4, IL-5, IL-6, KC (similar to human IL-8, IL-10, IL-12p40, IL-12p70, IL-13, IL-17, TNF-α, MCP-1, RANTES, IFN-γ and GM-CSF. Overall, cytokine concentrations were lower in serum than in BAL samples. By day 28, only KC was detected in BAL specimens at low concentrations in all groups. Administration of motavizumab significantly reduced (p

  7. Cancer Patient T Cells Genetically Targeted to Prostate-Specific Membrane Antigen Specifically Lyse Prostate Cancer Cells and Release Cytokines in Response to Prostate-Specific Membrane Antigen

    Directory of Open Access Journals (Sweden)

    Michael C. Gong

    1999-06-01

    Full Text Available The expression of immunoglobulin-based artificial receptors in normal T lymphocytes provides a means to target lymphocytes to cell surface antigens independently of major histocompatibility complex restriction. Such artificial receptors have been previously shown to confer antigen-specific tumoricidal properties in murine T cells. We constructed a novel ζ chain fusion receptor specific for prostate-specific membrane antigen (PSMA termed Pz-1. PSMA is a cell-surface glycoprotein expressed on prostate cancer cells and the neovascular endothelium of multiple carcinomas. We show that primary T cells harvested from five of five patients with different stages of prostate cancer and transduced with the Pz-1 receptor readily lyse prostate cancer cells. Having established a culture system using fibroblasts that express PSMA, we next show that T cells expressing the Pz-1 receptor release cytokines in response to cell-bound PSMA. Furthermore, we show that the cytokine release is greatly augmented by B7.1-mediated costimulation. Thus, our findings support the feasibility of adoptive cell therapy by using genetically engineered T cells in prostate cancer patients and suggest that both CD4+ and CD8+ T lymphocyte functions can be synergistically targeted against tumor cells.

  8. A Salmonella typhimurium ghost vaccine induces cytokine expression in vitro and immune responses in vivo and protects rats against homologous and heterologous challenges.

    Directory of Open Access Journals (Sweden)

    Nagarajan Vinod

    Full Text Available Salmonella enteritidis and Salmonella typhimurium are important food-borne bacterial pathogens, which are responsible for diarrhea and gastroenteritis in humans and animals. In this study, S. typhimurium bacterial ghost (STG was generated based on minimum inhibitory concentration (MIC of sodium hydroxide (NaOH. Experimental studies performed using in vitro and in vivo experimental model systems to characterize effects of STG as a vaccine candidate. When compared with murine macrophages (RAW 264.7 exposed to PBS buffer (98.1%, the macrophages exposed to formalin-killed inactivated cells (FKC, live wild-type bacterial cells and NaOH-induced STG at 1 × 108 CFU/mL showed 85.6%, 66.5% and 84.6% cell viability, respectively. It suggests that STG significantly reduces the cytotoxic effect of wild-type bacterial cells. Furthermore, STG is an excellent inducer for mRNAs of pro-inflammatory cytokine (TNF-α, IL-1β and factor (iNOS, anti-inflammatory cytokine (IL-10 and dual activities (IL-6 in the stimulated macrophage cells. In vivo, STG vaccine induced humoral and cellular immune responses and protection against homologous and heterologous challenges in rats. Furthermore, the immunogenicity and protective efficacy of STG vaccine were compared with those of FKC and non-vaccinated PBS control groups. The vaccinated rats from STG group exhibited higher levels of serum IgG antibody responses, serum bactericidal antibodies, and CD4+ and CD8+ T-cell populations than those of the FKC and PBS control groups. Most importantly, after challenge with homologous and heterologous strains, the bacterial loads in the STG group were markedly lower than the FKC and PBS control groups. In conclusion, these findings suggest that the STG vaccine induces protective immunity against homologous and heterologous challenges.

  9. Single-cell multiplexed cytokine profiling of CD19 CAR-T cells reveals a diverse landscape of polyfunctional antigen-specific response.

    Science.gov (United States)

    Xue, Qiong; Bettini, Emily; Paczkowski, Patrick; Ng, Colin; Kaiser, Alaina; McConnell, Timothy; Kodrasi, Olja; Quigley, Máire F; Heath, James; Fan, Rong; Mackay, Sean; Dudley, Mark E; Kassim, Sadik H; Zhou, Jing

    2017-11-21

    It remains challenging to characterize the functional attributes of chimeric antigen receptor (CAR)-engineered T cell product targeting CD19 related to potency and immunotoxicity ex vivo, despite promising in vivo efficacy in patients with B cell malignancies. We employed a single-cell, 16-plex cytokine microfluidics device and new analysis techniques to evaluate the functional profile of CD19 CAR-T cells upon antigen-specific stimulation. CAR-T cells were manufactured from human PBMCs transfected with the lentivirus encoding the CD19-BB-z transgene and expanded with anti-CD3/anti-CD28 coated beads. The enriched CAR-T cells were stimulated with anti-CAR or control IgG beads, stained with anti-CD4 RPE and anti-CD8 Alexa Fluor 647 antibodies, and incubated for 16 h in a single-cell barcode chip (SCBC). Each SCBC contains ~12,000 microchambers, covered with a glass slide that was pre-patterned with a complete copy of a 16-plex antibody array. Protein secretions from single CAR-T cells were captured and subsequently analyzed using proprietary software and new visualization methods. We demonstrate a new method for single-cell profiling of CD19 CAR-T pre-infusion products prepared from 4 healthy donors. CAR-T single cells exhibited a marked heterogeneity of cytokine secretions and polyfunctional (2+ cytokine) subsets specific to anti-CAR bead stimulation. The breadth of responses includes anti-tumor effector (Granzyme B, IFN-γ, MIP-1α, TNF-α), stimulatory (GM-CSF, IL-2, IL-8), regulatory (IL-4, IL-13, IL-22), and inflammatory (IL-6, IL-17A) functions. Furthermore, we developed two new bioinformatics tools for more effective polyfunctional subset visualization and comparison between donors. Single-cell, multiplexed, proteomic profiling of CD19 CAR-T product reveals a diverse landscape of immune effector response of CD19 CAR-T cells to antigen-specific challenge, providing a new platform for capturing CAR-T product data for correlative analysis. Additionally, such high

  10. Transient response and radiation dose estimates for breaches to a spent fuel processing facility

    Energy Technology Data Exchange (ETDEWEB)

    Solbrig, Charles W., E-mail: soltechco@aol.com; Pope, Chad; Andrus, Jason

    2014-08-15

    Highlights: • We model doses received from a nuclear fuel facility from boundary leaks due to an earthquake. • The supplemental exhaust system (SES) starts after breach causing air to be sucked into the cell. • Exposed metal fuel burns increasing pressure and release of radioactive contamination. • Facility releases are small and much less than the limits showing costly refits are unnecessary. • The method presented can be used in other nuclear fuel processing facilities. - Abstract: This paper describes the analysis of the design basis accident for Idaho National Laboratory Fuel Conditioning Facility (FCF). The facility is used to process spent metallic nuclear fuel. This analysis involves a model of the transient behavior of the FCF inert atmosphere hot cell following an earthquake initiated breach of pipes passing through the cell boundary. Such breaches allow the introduction of air and subsequent burning of pyrophoric metals. The model predicts the pressure, temperature, volumetric releases, cell heat transfer, metal fuel combustion, heat generation rates, radiological releases and other quantities. The results show that releases from the cell are minimal and satisfactory for safety. This analysis method should be useful in other facilities that have potential for damage from an earthquake and could eliminate the need to back fit facilities with earthquake proof boundaries or lessen the cost of new facilities.

  11. Transient response and radiation dose estimates for breaches to a spent fuel processing facility

    International Nuclear Information System (INIS)

    Solbrig, Charles W.; Pope, Chad; Andrus, Jason

    2014-01-01

    Highlights: • We model doses received from a nuclear fuel facility from boundary leaks due to an earthquake. • The supplemental exhaust system (SES) starts after breach causing air to be sucked into the cell. • Exposed metal fuel burns increasing pressure and release of radioactive contamination. • Facility releases are small and much less than the limits showing costly refits are unnecessary. • The method presented can be used in other nuclear fuel processing facilities. - Abstract: This paper describes the analysis of the design basis accident for Idaho National Laboratory Fuel Conditioning Facility (FCF). The facility is used to process spent metallic nuclear fuel. This analysis involves a model of the transient behavior of the FCF inert atmosphere hot cell following an earthquake initiated breach of pipes passing through the cell boundary. Such breaches allow the introduction of air and subsequent burning of pyrophoric metals. The model predicts the pressure, temperature, volumetric releases, cell heat transfer, metal fuel combustion, heat generation rates, radiological releases and other quantities. The results show that releases from the cell are minimal and satisfactory for safety. This analysis method should be useful in other facilities that have potential for damage from an earthquake and could eliminate the need to back fit facilities with earthquake proof boundaries or lessen the cost of new facilities

  12. Transient response of small molten salt reactor at duct blockage accident

    International Nuclear Information System (INIS)

    Yamamoto, Takahisa; Mitachi, Koshi; Ikeuchi, Koji; Suzuki, Takashi

    2005-01-01

    This paper performed transient core analysis of a small Molten Salt Reactor (MSR) at the time of a duct blockage accident. The numerical model employed in this study consists of continuity and momentum conservation equations for fuel salt flow, two group diffusion equations for fast and thermal neutron fluxes, balance equations for six-group delayed neutron precursors and energy conservation equations for fuel salt and graphite moderator. The analysis shows that (1) the effective multiplication factor and reactor power after the blockage accident hardly change because of the self-control performance of the MSR, (2) fuel salt and graphite moderator temperatures rise at the blockage point and its vicinity, drastically but locally, (3) the highest temperature after the blockage accident is 1 363 K, very lower than the boiling point of fuel salt and melt point of reactor vessel, (4) fast and thermal neutron fluxes distributions after the blockage accident hardly change, and (5) delayed neutron precursors accumulate at the blockage point, especially 1st delayed neutron precursor due to is large decay constant. These results lead that the safety of MSR is assured in the blockage accident. (author)

  13. INTRANS. A computer code for the non-linear structural response analysis of reactor internals under transient loads

    International Nuclear Information System (INIS)

    Ramani, D.T.

    1977-01-01

    The 'INTRANS' system is a general purpose computer code, designed to perform linear and non-linear structural stress and deflection analysis of impacting or non-impacting nuclear reactor internals components coupled with reactor vessel, shield building and external as well as internal gapped spring support system. This paper describes in general a unique computational procedure for evaluating the dynamic response of reactor internals, descretised as beam and lumped mass structural system and subjected to external transient loads such as seismic and LOCA time-history forces. The computational procedure is outlined in the INTRANS code, which computes component flexibilities of a discrete lumped mass planar model of reactor internals by idealising an assemblage of finite elements consisting of linear elastic beams with bending, torsional and shear stiffnesses interacted with external or internal linear as well as non-linear multi-gapped spring support system. The method of analysis is based on the displacement method and the code uses the fourth-order Runge-Kutta numerical integration technique as a basis for solution of dynamic equilibrium equations of motion for the system. During the computing process, the dynamic response of each lumped mass is calculated at specific instant of time using well-known step-by-step procedure. At any instant of time then, the transient dynamic motions of the system are held stationary and based on the predicted motions and internal forces of the previous instant. From which complete response at any time-step of interest may then be computed. Using this iterative process, the relationship between motions and internal forces is satisfied step by step throughout the time interval

  14. Nonlinear transient dynamic response of pressure relief valves for a negative containment system

    International Nuclear Information System (INIS)

    Aziz, T.S.; Duff, C.G.; Tang, J.H.K.

    1979-01-01

    The response of the piston for the postulated simultaneous effect of pressure and an earthquake is obtained for different parameters and accident conditions. Response quantities such as accelerations, displacements, rotations, diaphragm forces as well as opening time during a design basis earthquake are obtained. The results of the different analyses, as related to the functional operability of the valves, are evaluated and discussed. (orig.)

  15. Effect of Scoparia dulcis on noise stress induced adaptive immunity and cytokine response in immunized Wistar rats.

    Science.gov (United States)

    Sundareswaran, Loganathan; Srinivasan, Sakthivel; Wankhar, Wankupar; Sheeladevi, Rathinasamy

    Noise acts as a stressor and is reported to have impact on individual health depending on nature, type, intensity and perception. Modern medicine has no effective drugs or cure to prevent its consequences. Being an environmental stressor noise cannot be avoided; instead minimizing its exposure or consuming anti-stressor and adaptogens from plants can be considered. The present study was carried out to evaluate the anti-stressor, adaptogen and immunostimulatory activity of Scoparia dulcis against noise-induced stress in Wistar rat models. Noise stress in rats was created by broadband white noise generator, 100 dB A/4 h daily/15 days and S. dulcis (200 mg/kg b.w.) was administered orally. 8 groups of rats were used consisting of 6 animals each; 4 groups for unimmunized and 4 groups for immunized. For immunization, sheep red blood cells (5 × 10 9  cells/ml) were injected intraperitoneally. Sub-acute noise exposed rats showed a significant increase in corticosterone and IL-4 levels in both immunized and unimmunized rats whereas lymphocytes, antibody titration, soluble immune complex, IL-4 showed a marked increase with a significant decrease in IL-2, TNF-α, IFN-γ cytokines only in unimmunized rats. Immunized noise exposed rats presented increased leukocyte migration index and decreased foot pad thickness, IL-2, TNF-α, IFN-γ with no changes in the lymphocytes. S. dulcis (SD) has normalized and prevented the noise induced changes in cell-mediated and humoral immunity and it could be the presence of anti-stressor and immuno stimulant activity of the plant. Copyright © 2016 Transdisciplinary University, Bangalore and World Ayurveda Foundation. Published by Elsevier B.V. All rights reserved.

  16. Skewed Helper T-Cell Responses to IL-12 Family Cytokines Produced by Antigen-Presenting Cells and the Genetic Background in Behcet’s Disease

    Directory of Open Access Journals (Sweden)

    Jun Shimizu

    2013-01-01

    Full Text Available Behcet’s disease (BD is a multisystemic inflammatory disease and is characterized by recurrent attacks on eyes, brain, skin, and gut. There is evidence that skewed T-cell responses contributed to its pathophysiology in patients with BD. Recently, we found that Th17 cells, a new helper T (Th cell subset, were increased in patients with BD, and both Th type 1 (Th1 and Th17 cell differentiation signaling pathways were overactivated. Several researches revealed that genetic polymorphisms in Th1/Th17 cell differentiation signaling pathways were associated with the onset of BD. Here, we summarize current findings on the Th cell subsets, their contribution to the pathogenesis of BD and the genetic backgrounds, especially in view of IL-12 family cytokine production and pattern recognition receptors of macrophages/monocytes.

  17. Cytokine responses in primary chicken embryo intestinal cells infected with Campylobacter jejuni strains of human and chicken origin and the expression of bacterial virulence-associated genes

    DEFF Research Database (Denmark)

    Li, Yiping; Ingmer, Hanne; Madsen, Mogens

    2008-01-01

    of the bacterial genes. We have investigated the invasiveness of primary chicken embryo intestinal cells (CEICs) by C. jejuni strains of human and chicken origins and the production of pro-inflammatory cytokines as well as the expression of the bacterial virulence-associated genes during co-cultivation. Results C......-free media from another co-cultivation experiment also increased the expression of the virulence-associated genes in the C. jejuni chicken isolate, indicating that the expression of bacterial genes is regulated by component(s) secreted upon co-cultivation of bacteria and CEICs. Conclusion We show that under...... in vitro culture condition C. jejuni strains of both human and chicken origins can invade avian host cells with a pro-inflammatory response and that the virulence-associated genes of C. jejuni may play a role in this process....

  18. Transient Thermal Response of Lightweight Cementitious Composites Made with Polyurethane Foam Waste

    Science.gov (United States)

    Kismi, M.; Poullain, P.; Mounanga, P.

    2012-07-01

    The development of low-cost lightweight aggregate (LWA) mortars and concretes presents many advantages, especially in terms of lightness and thermal insulation performances of structures. Low-cost LWA mainly comes from the recovery of vegetal or plastic wastes. This article focuses on the characterization of the thermal conductivity of innovative lightweight cementitious composites made with fine particles of rigid polyurethane (PU) foam waste. Five mortars were prepared with various mass substitution rates of cement with PU-foam particles. Their thermal conductivity was measured with two transient methods: the heating-film method and the hot-disk method. The incorporation of PU-foam particles causes a reduction of up to 18 % of the mortar density, accompanied by a significant improvement of the thermal insulating performance. The effect of segregation on the thermal properties of LWA mortars due to the differences of density among the cementitious matrix, sand, and LWA has also been quantified. The application of the hot-disk method reveals a gradient of thermal conductivity along the thickness of the specimens, which could be explained by a non-uniform repartition of fine PU-foam particles and mineral aggregates within the mortars. The results show a spatial variation of the thermal conductivity of the LWA mortars, ranging from 9 % to 19 %. However, this variation remains close to or even lower than that observed on a normal weight aggregate mortar. Finally, a self-consistent approach is proposed to estimate the thermal conductivity of PU-foam cement-based composites.

  19. Transient and steady state creep response of ice I and magnesium sulfate hydrate eutectic aggregates

    Science.gov (United States)

    McCarthy, C.; Cooper, R.F.; Goldsby, D.L.; Durham, W.B.; Kirby, S.H.

    2011-01-01

    Using uniaxial compression creep experiments, we characterized the transient and steady state deformation behaviors of eutectic aggregates of system ice I and MgSO4 11H2O (MS11; meridianiite), which has significance because of its likely presence on moons of the outer solar system. Synthetic samples of eutectic liquid bulk composition, which produce eutectic colonies containing 0.35-0.50 volume fraction MS11, were tested as functions of colony size and lamellar spacing, temperature (230-250 K), and confining pressure (0.1 and 50 MPa) to strains ???0.2. Up to a differential stress of 6 MPa, the ice I-MS11 aggregates display an order of magnitude higher effective viscosity and higher stress sensitivity than do aggregates of pure polycrystalline ice at the same conditions. The creep data and associated microstructural observations demonstrate, however, that the aggregates are additionally more brittle than pure ice, approaching rate-independent plasticity that includes rupture of the hydrate phase at 6-8 MPa, depending on the scale of the microstructure. Microstructures of deformed samples reveal forms of semibrittle flow in which the hydrate phase fractures while the ice phase deforms plastically. Semibrittle flow in the icy shell of a planetary body would truncate the lithospheric strength envelope and thereby decrease the depth to the brittle-ductile transition by 55% and reduce the failure limit for compressional surface features from 10 to ???6 MPa. A constitutive equation that includes eutectic colony boundary sliding and intracolony flow is used to describe the steady state rheology of the eutectic aggregates. Copyright ?? 2011 by the American Geophysical Union.

  20. Implications of oxidative stress and hepatic cytokine (TNF-α and IL-6) response in the pathogenesis of hepatic collagenesis in chronic arsenic toxicity

    International Nuclear Information System (INIS)

    Das, Subhankar; Santra, Amal; Lahiri, Sarbari; Guha Mazumder, D.N.

    2005-01-01

    Introduction: Noncirrhotic portal fibrosis has been reported to occur in humans due to prolonged intake of arsenic contaminated water. Further, oxystress and hepatic fibrosis have been demonstrated by us in chronic arsenic induced hepatic damage in murine model. Cytokines like tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6) are suspected to play a role in hepatic collagenesis. The present study has been carried out to find out whether increased oxystress and cytokine response are associated with increased accumulation of collagen in the liver due to prolonged arsenic exposure and these follow a dose-response relationship. Methods: Male BALB/c mice were given orally 200 μl of water containing arsenic in a dose of 50, 100, and 150 μg/mouse/day for 6 days a week (experimental group) or arsenic-free water (<0.01 μg/l, control group) for 3, 6, 9 and 12 months. Hepatic glutathione (GSH), protein sulfhydryl (PSH), glutathione peroxidase (GPx), Catalase, lipid peroxidation (LPx), protein carbonyl (PC), interleukin (IL-6), tumor necrosis factor (TNF-α), arsenic and collagen content in the liver were estimated from sacrificed animals. Results: Significant increase of lipid peroxidation and protein oxidation in the liver associated with depletion of hepatic thiols (GSH, PSH), and antioxidant enzymes (GPx, Catalase) occurred in mice due to prolonged arsenic exposure in a dose-dependent manner. Significant elevation of hepatic collagen occurred at 9 and 12 months in all the groups associated with significant elevation of TNF-α and IL-6. However, arsenic level in the liver increased progressively from 3 months onwards. There was a positive correlation between the hepatic arsenic level and collagen content (r = 0.8007), LPx (r = 0.779) and IL-6 (r = 0.7801). Further, there was a significant negative correlation between GSH and TNF-α (r = -0.5336)) and LPx (r = -0.644). Conclusion: Increasing dose and duration of arsenic exposure in mice cause progressive increase

  1. Transcriptional 'memory' of a stress: transient chromatin and memory (epigenetic) marks at stress-response genes.

    Science.gov (United States)

    Avramova, Zoya

    2015-07-01

    Drought, salinity, extreme temperature variations, pathogen and herbivory attacks are recurring environmental stresses experienced by plants throughout their life. To survive repeated stresses, plants provide responses that may be different from their response during the first encounter with the stress. A different response to a similar stress represents the concept of 'stress memory'. A coordinated reaction at the organismal, cellular and gene/genome levels is thought to increase survival chances by improving the plant's tolerance/avoidance abilities. Ultimately, stress memory may provide a mechanism for acclimation and adaptation. At the molecular level, the concept of stress memory indicates that the mechanisms responsible for memory-type transcription during repeated stresses are not based on repetitive activation of the same response pathways activated by the first stress. Some recent advances in the search for transcription 'memory factors' are discussed with an emphasis on super-induced dehydration stress memory response genes in Arabidopsis. © 2015 The Author The Plant Journal © 2015 John Wiley & Sons Ltd.

  2. Increased Age, but Not Parity Predisposes to Higher Bacteriuria Burdens Due to Streptococcus Urinary Tract Infection and Influences Bladder Cytokine Responses, Which Develop Independent of Tissue Bacterial Loads.

    Science.gov (United States)

    Sullivan, Matthew J; Carey, Alison J; Leclercq, Sophie Y; Tan, Chee K; Ulett, Glen C

    2016-01-01

    Streptococcus agalactiae causes urinary tract infection (UTI) in pregnant adults, non-pregnant adults, immune-compromised individuals and the elderly. The pathogenesis of S. agalactiae UTI in distinct patient populations is poorly understood. In this study, we used murine models of UTI incorporating young mice, aged and dam mice to show that uropathogenic S. agalactiae causes bacteriuria at significantly higher levels in aged mice compared to young mice and this occurs coincident with equivalent levels of bladder tissue colonisation at 24 h post-infection (p.i.). In addition, aged mice exhibited significantly higher bacteriuria burdens at 48 h compared to young mice, confirming a divergent pattern of bacterial colonization in the urinary tract of aged and young mice. Multiparous mice, in contrast, exhibited significantly lower urinary titres of S. agalactiae compared to age-matched nulliparous mice suggesting that parity enhances the ability of the host to control S. agalactiae bacteriuria. Additionally, we show that both age and parity alter the expression levels of several key regulatory and pro-inflammatory cytokines, which are known to be important the immune response to UTI, including Interleukin (IL)-1β, IL-12(p40), and Monocyte Chemoattractant Protein-1 (MCP-1). Finally, we demonstrate that other cytokines, including IL-17 are induced significantly in the S. agalactiae-infected bladder regardless of age and parity status. Collectively, these findings show that the host environment plays an important role in influencing the severity of S. agalactiae UTI; infection dynamics, particularly in the context of bacteriuria, depend on age and parity, which also affect the nature of innate immune responses to infection.

  3. Change in autoantibody and cytokine responses during the evolution of neuromyelitis optica in patients with systemic lupus erythematosus

    DEFF Research Database (Denmark)

    Kovacs, Katalin T; Kalluri, Sudhakar Reddy; Boza-Serrano, Antonio

    2016-01-01

    BACKGROUND: Neuromyelitis optica (NMO)-systemic lupus erythematosus (SLE) association is a rare condition characterized by multiple autoantibodies. OBJECTIVE: To examine if, during the evolution of NMO, anti-AQP4 responses are part of polyclonal B cell activation, and if T cell responses contribute...

  4. Improved outcome of chronic Pseudomonas aeruginosa lung infection is associated with induction of a Th1-dominated cytokine response

    DEFF Research Database (Denmark)

    Moser, C; Jensen, P O; Kobayashi, O

    2002-01-01

    , resistance to re-infection was paralleled by a shift towards a Th1-dominated response and increased IL-12 production. No significant increase in serum IgG was observed in the re-infected mice. In conclusion, these results indicate a protective role for a Th1-dominated response, independent of antibody...

  5. Ex vivo inhibited cytokine profiling may explain inferior treatment response to golimumab after adalimumab failure in rheumatoid arthritis

    NARCIS (Netherlands)

    Tweehuysen, L; Schraa, K.; Netea, M.G.; Hoogen, F.H.J. van den; Joosten, L.A.B.; Broeder, A.A. den

    2018-01-01

    OBJECTIVES: Clinical data suggest that the response of rheumatoid arthritis patients to treatment with golimumab is much lower among those who switched from adalimumab than among those who switched from etanercept. To elucidate the mechanism behind this difference in response to sequential biologic

  6. The influence of a scaled boundary response on integral system transient behavior

    International Nuclear Information System (INIS)

    Dimenna, R.A.; Kullberg, C.M.

    1989-01-01

    Scaling relationships associated with the thermal-hydraulic response of a closed-loop system are applied to a calculational assessment of a feed-and-bleed recovery in a nuclear reactor integral effects test. The analysis demonstrates both the influence of scale on the system response and the ability of the thermal-hydraulics code to represent those effects. The qualitative response of the fluid is shown to be coupled to the behavior of the bounding walls through the energy equation. The results of the analysis described in this paper influence the determination of computer code applicability. The sensitivity of the code response to scaling variations introduced in the analysis is found to be appropriate with respect to scaling criteria determined from the scaling literature. Differences in the system response associated with different scaling criteria are found to be plausible and easily explained using well-known principles of heat transfer. Therefore, it is concluded that RELAP5/MOD2 can adequately represent the scaled effects of heat transfer boundary conditions of the thermal-hydraulic calculations through the mechanism of communicating walls. The results of the analysis also serve to clarify certain aspects of experiment and facility design

  7. Proposing Wavelet-Based Low-Pass Filter and Input Filter to Improve Transient Response of Grid-Connected Photovoltaic Systems

    Directory of Open Access Journals (Sweden)

    Bijan Rahmani

    2016-08-01

    Full Text Available Available photovoltaic (PV systems show a prolonged transient response, when integrated into the power grid via active filters. On one hand, the conventional low-pass filter, employed within the integrated PV system, works with a large delay, particularly in the presence of system’s low-order harmonics. On the other hand, the switching of the DC (direct current–DC converters within PV units also prolongs the transient response of an integrated system, injecting harmonics and distortion through the PV-end current. This paper initially develops a wavelet-based low-pass filter to improve the transient response of the interconnected PV systems to grid lines. Further, a damped input filter is proposed within the PV system to address the raised converter’s switching issue. Finally, Matlab/Simulink simulations validate the effectiveness of the proposed wavelet-based low-pass filter and damped input filter within an integrated PV system.

  8. Citoquinas reguladoras de la respuesta al transplante renal alogénico Regulatory cytokines in the response to the allogeneic renal transplant

    Directory of Open Access Journals (Sweden)

    Rita L. Cardoni

    2005-03-01

    Full Text Available La aceptación o el rechazo del riñón alogénico dependen principalmente de la respuesta inmune y de su compleja regulación en la cual la red de citoquinas y otros mediadores juegan un importante papel. Actualmente, la biopsia renal es, a pesar de lo invasor del procedimiento, la herramienta de mayor utilidad para el control del rechazo al trasplante y el diagnóstico de las nefropatías asociadas. Por ello, es de gran interés encontrar métodos alternativos para el diagnóstico. La evaluación de citoquinas reguladoras de la respuesta inmune es un procedimiento sencillo y de bajo costo que podría ser de utilidad para incrementar la sensibilidad de la detección de diferencias polimórficas, para pronosticar la aceptación del trasplante y para la detección precoz del rechazo. Los estudios recientes sugieren que la producción exagerada de mediadores pro-inflamatorios, incluyendo a citoquinas Th1, sería desventajosa para la sobrevida del trasplante, mientras que la producción de citoquinas reguladoras anti-inflamatorias, como la interleuquina (IL-10 y el factor de crecimiento tumoral (TGF-b, sería beneficiosa. En las primeras etapas, la respuesta Th1 puede incrementar la actividad citotóxica y la detección de moléculas citotóxicas está asociada al rechazo agudo. Luego podría ser más importante considerar el balance entre la producción de mediadores pro- y anti-inflamatorios y la regulación de sus niveles. Así, el TGF-b es también fibrogénico y su excesiva producción local puede contribuir al daño renal. Por otro lado, el incremento de la producción de IL-10 en respuesta al estímulo alogénico sería, en la mayoría de los casos, un marcador importante para pronosticar la aceptación prolongada.The outcome of the kidney allograft mainly depends on the immune response and on its complex regulation, where the cytokine network and other mediators play an important role. At present, kidney biopsy is the most useful tool for

  9. Ki-67 expression reveals strong, transient influenza specific CD4 T cell responses after adult vaccination

    OpenAIRE

    Li, Xi; Miao, Hongyu; Henn, Alicia; Topham, David J.; Wu, Hulin; Zand, Martin S.; Mosmann, Tim R.

    2012-01-01

    Although previous studies have found minimal changes in CD4 T cell responses after vaccination of adults with trivalent inactivated influenza vaccine, daily sampling and monitoring of the proliferation marker Ki-67 have now been used to reveal that a substantial fraction of influenza-specific CD4 T cells respond to vaccination. At 4–6 days after vaccination, there is a sharp rise in the numbers of Ki-67-expressing PBMC that produce IFNγ, IL-2 and/or TNFα in vitro in response to influenza vacc...

  10. Cytokines as cellular communicators

    Directory of Open Access Journals (Sweden)

    R. Debets

    1996-01-01

    Full Text Available Cytokines and their receptors are involved in the pathophysiology of many diseases. Here we present a detailed review on cytokines, receptors and signalling routes, and show that one important lesson from cytokine biology is the complex and diverse regulation of cytokine activity. The activity of cytokines is controlled at the level of transcription, translation, storage, processing, posttranslational modification, trapping, binding by soluble proteins, and receptor number and/or function. Translation of this diverse regulation in strategies aimed at the control of cytokine activity will result in the development of more specific and selective drugs to treat diseases.

  11. Sperm Cells Induce Distinct Cytokine Response in Peripheral Mononuclear Cells from Infertile Women with Serum Anti-Sperm Antibodies

    Czech Academy of Sciences Publication Activity Database

    Kverka, Miloslav; Ulčová-Gallová, Z.; Bártová, J.; Cibulka, J.; Bibková, K.; Mičanová, Z.; Tlaskalová-Hogenová, Helena

    2012-01-01

    Roč. 7, č. 8 (2012), e44172 E-ISSN 1932-6203 Institutional support: RVO:61388971 Keywords : IMMUNE-RESPONSES * GROWTH-FACTOR * ENDOMETRIOSIS Subject RIV: EC - Immunology Impact factor: 3.730, year: 2012

  12. Biogeochemical Processes Responsible for the Enhanced Transport of Plutonium Under transient Unsaturated Ground Water Conditions

    Energy Technology Data Exchange (ETDEWEB)

    Fred J. Molz, III

    2010-05-28

    To better understand longer-term vadose zone transport in southeastern soils, field lysimeter experiments were conducted at the Savannah River Site (SRS) near Aiken, SC, in the 1980s. Each of the three lysimeters analyzed herein contained a filter paper spiked with different Pu solutions, and they were left exposed to natural environmental conditions (including the growth of annual weed grasses) for 11 years. The resulting Pu activity measurements from each lysimeter core showed anomalous activity distributions below the source, with significant migration of Pu above the source. Such results are not explainable by adsorption phenomena alone. A transient variably saturated flow model with root water uptake was developed and coupled to a soil reactive transport model. Somewhat surprisingly, the fully transient analysis showed results nearly identical to those of a much simpler steady flow analysis performed previously. However, all phenomena studied were unable to produce the upward Pu transport observed in the data. This result suggests another transport mechanism such as Pu uptake by roots and upward transport due to transpiration. Thus, the variably saturated flow and reactive transport model was extended to include uptake and transport of Pu within the root xylem, along with computational methodology and results. In the extended model, flow velocity in the soil was driven by precipitation input along with transpiration and drainage. Water uptake by the roots determined the flow velocity in the root xylem, and this along with uptake of Pu in the transpiration stream drove advection and dispersion of the two Pu species in the xylem. During wet periods with high potential evapotranspiration, maximum flow velocities through the xylem would approached 600 cm/hr, orders of magnitude larger that flow velocities in the soil. Values for parameters and the correct conceptual viewpoint for Pu transport in plant xylem was uncertain. This motivated further experiments devoted

  13. Biogeochemical Processes Responsible for the Enhanced Transport of Plutonium Under transient Unsaturated Ground Water Conditions

    International Nuclear Information System (INIS)

    Molz, Fred J. III

    2010-01-01

    To better understand longer-term vadose zone transport in southeastern soils, field lysimeter experiments were conducted at the Savannah River Site (SRS) near Aiken, SC, in the 1980s. Each of the three lysimeters analyzed herein contained a filter paper spiked with different Pu solutions, and they were left exposed to natural environmental conditions (including the growth of annual weed grasses) for 11 years. The resulting Pu activity measurements from each lysimeter core showed anomalous activity distributions below the source, with significant migration of Pu above the source. Such results are not explainable by adsorption phenomena alone. A transient variably saturated flow model with root water uptake was developed and coupled to a soil reactive transport model. Somewhat surprisingly, the fully transient analysis showed results nearly identical to those of a much simpler steady flow analysis performed previously. However, all phenomena studied were unable to produce the upward Pu transport observed in the data. This result suggests another transport mechanism such as Pu uptake by roots and upward transport due to transpiration. Thus, the variably saturated flow and reactive transport model was extended to include uptake and transport of Pu within the root xylem, along with computational methodology and results. In the extended model, flow velocity in the soil was driven by precipitation input along with transpiration and drainage. Water uptake by the roots determined the flow velocity in the root xylem, and this along with uptake of Pu in the transpiration stream drove advection and dispersion of the two Pu species in the xylem. During wet periods with high potential evapotranspiration, maximum flow velocities through the xylem would approached 600 cm/hr, orders of magnitude larger that flow velocities in the soil. Values for parameters and the correct conceptual viewpoint for Pu transport in plant xylem was uncertain. This motivated further experiments devoted

  14. Diffuse-charge effects on the transient response of electrochemical cells

    NARCIS (Netherlands)

    Soestbergen, M.; Biesheuvel, P.M.; Bazant, M.Z.

    2010-01-01

    We present theoretical models for the time-dependent voltage of an electrochemical cell in response to a current step, including effects of diffuse charge (or “space charge”) near the electrodes on Faradaic reaction kinetics. The full model is based on the classical Poisson-Nernst-Planck equations

  15. Transient impairment of the adaptive response to fasting in FXR-deficient mice

    NARCIS (Netherlands)

    Cariou, B; van Harmelen, K; Duran-Sandoval, D; van Dijk, T; Grefhorst, A; Bouchaert, E; Fruchart, JC; Gonzalez, FJ; Kuipers, F; Staels, B

    2005-01-01

    The farnesoid X receptor (FXR) has been suggested to play a role in gluconeogenesis. To determine whether FXR modulates the response to fasting in vivo, FXR-deficient (FXR-/-) and wild-type mice were submitted to fasting for 48 h. Our results demonstrate that FXR modulates the kinetics of

  16. Ki-67 expression reveals strong, transient influenza specific CD4 T cell responses after adult vaccination.

    Science.gov (United States)

    Li, Xi; Miao, Hongyu; Henn, Alicia; Topham, David J; Wu, Hulin; Zand, Martin S; Mosmann, Tim R

    2012-06-29

    Although previous studies have found minimal changes in CD4 T cell responses after vaccination of adults with trivalent inactivated influenza vaccine, daily sampling and monitoring of the proliferation marker Ki-67 have now been used to reveal that a substantial fraction of influenza-specific CD4 T cells respond to vaccination. At 4-6 days after vaccination, there is a sharp rise in the numbers of Ki-67-expressing PBMC that produce IFNγ, IL-2 and/or TNFα in vitro in response to influenza vaccine or peptide. Ki-67(+) cell numbers then decline rapidly, and 10 days after vaccination, both Ki-67(+) and overall influenza-specific cell numbers are similar to pre-vaccination levels. These results provide a tool for assessing the quality and quantity of CD4 T cell responses to different influenza vaccines, and raise the possibility that the anti-influenza T cell memory response may be qualitatively altered by vaccination, even if the overall memory cell numbers do not change significantly. Copyright © 2012. Published by Elsevier Ltd.

  17. Analysis of the Kinetics and Regulation of Cytokine Gene Expression During the Primary In Vivo Immune Response to Killed Brucella Abortus

    Science.gov (United States)

    1992-08-10

    Purified protein derivative of Mycobacterium tuberculosis and excretory-secretory antigen(s) of Toxocara canis expand in vitro human T cells with...day after immunization viii 47 49 LIST OF TABLES I. PCR primers and Southern blot probes of Th 11Th2 cytokines II. Cytokine mRNA levels in Thyl...sensitive quantitative reverse transcriptase-polymerase chain reaction (RT- PCR ) assay to measure changes in Thl and Th2 cytokine gene expression during

  18. Transfusion-associated immunomodulation: Quantitative changes in cytokines as a measure of immune responsiveness after one time blood transfusion in neurosurgery patients

    Directory of Open Access Journals (Sweden)

    Pandey Prashant

    2010-01-01

    Full Text Available Very few studies in humans have investigated the laboratory evidences suggestive of transfusion-associated immunologic changes. In this prospective study, we examined the effects of perioperative blood transfusion on immune response, by measuring various cytokines production, namely, interferon-gamma (IFN-γ, interleukin-10 (IL-10, and Fas Ligand (FasL. A total of 40 patients undergoing neurosurgery were randomly allocated into four groups: (a no transfusion, (b allogeneic non-leukofiltered transfusion, (c prestorage leukofiltered transfusion, (d autologous transfusion. Samples were collected before operation (day 0 and postoperative days (post-op 1, 7, and 14. IFN-γ and IL-10 production capacity was measured in supernatant after whole blood culture and serum FasL levels in patients′ sera using commercially available ELISA kits. Change in ratios (cytokine value after PHA stimulation/control value of IFN-γ and IL-10 and percentage change from baseline for serum FasL levels across different transfusion groups during the sampling period were calculated. There was an increase in IL-10 production in patients receiving allogeneic non-leukofiltered transfusion on days 1 and 7 (mean ratio 2.22 (± 2.16, 4.12 (± 1.71, 4.46 (± 1.97 on days 0, 1, and 7, respectively. Similarly there was a significant (P<0.05 decrease in IFN-γ production in patients who received allogeneic non-leukofiltered red cell transfusion on post-op days 1, 7, and 14 (mean ratio 6.88 (± 4.56, 2.53 (± 0.95, 3.04 (± 1.38 and 2.58 (± 1.48 on day 0, 1, 7, and 14, respectively. Serum FasL production was increased across all patients till 7th day except for ′no transfusion′ group and this increase was most significant in the non-leukofiltered group. We conclude that one time transfusion leads to quantitative changes in levels of these cytokines largely through interplay of Th2/Th1 pathways in allogeneic nonleukofiltered blood transfusion; however, soluble mediators like Fas

  19. Transient and Prolonged Response of Chicken Cecum Mucosa to Colonization with Different Gut Microbiota

    Science.gov (United States)

    Volf, Jiri; Polansky, Ondrej; Varmuzova, Karolina; Gerzova, Lenka; Sekelova, Zuzana; Faldynova, Marcela; Babak, Vladimir; Medvecky, Matej; Smith, Adrian L.; Kaspers, Bernd; Velge, Philippe; Rychlik, Ivan

    2016-01-01

    In this study we determined protein and gene expression in the caeca of newly hatched chickens inoculated with cecal contents sourced from hens of different ages. Over 250 proteins exhibited modified expression levels in response to microbiota inoculation. The most significant inductions were observed for ISG12-2, OASL, ES1, LYG2, DMBT1-L, CDD, ANGPTL6, B2M, CUZD1, IgM and Ig lambda chain. Of these, ISG12-2, ES1 and both immunoglobulins were expressed at lower levels in germ-free chickens compared to conventional chickens. In contrast, CELA2A, BRT-2, ALDH1A1, ADH1C, AKR1B1L, HEXB, ALDH2, ALDOB, CALB1 and TTR were expressed at lower levels following inoculation of microbiota. When chicks were given microbiota preparations from different age donors, the recipients mounted differential responses to the inoculation which also differed from the response profile in naturally colonised birds. For example, B2M, CUZD1 and CELA2A responded differently to the inoculation with microbiota of 4- or 40-week-old hens. The increased or decreased gene expression could be recorded 6 weeks after the inoculation of newly hatched chickens. To characterise the proteins that may directly interact with the microbiota we characterised chicken proteins that co-purified with the microbiota and identified a range of host proteins including CDD, ANGPTL6, DMBT1-L, MEP1A and Ig lambda. We propose that induction of ISG12-2 results in reduced apoptosis of host cells exposed to the colonizing commensal microbiota and that CDD, ANGPTL6, DMBT1-L, MEP1A and Ig lambda reduce contact of luminal microbiota with the gut epithelium thereby reducing the inflammatory response. PMID:27685470

  20. Predicting decadal trends and transient responses of radiocarbon storage and fluxes in a temperate forest soil

    OpenAIRE

    Sierra, C. A.; Trumbore, S. E.; Davidson, E. A.; Frey, S. D.; Savage, K. E.; Hopkins, F. M.

    2012-01-01

    Representing the response of soil carbon dynamics to global environmental change requires the incorporation of multiple tools in the development of predictive models. An important tool to construct and test models is the incorporation of bomb radiocarbon in soil organic matter during the past decades. In this manuscript, we combined radiocarbon data and a previously developed empirical model to explore decade-scale soil carbon dyn...

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

    Science.gov (United States)

    Nandi, Ajeya; Bishayi, Biswadev

    2017-05-01

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

  2. Kluyveromyces marxianus and Saccharomyces boulardii Induce Distinct Levels of Dendritic Cell Cytokine Secretion and Significantly Different T Cell Responses In Vitro.

    Directory of Open Access Journals (Sweden)

    Ida M Smith

    Full Text Available Interactions between members of the intestinal microbiota and the mucosal immune system can significantly impact human health, and in this context, fungi and food-related yeasts are known to influence intestinal inflammation through direct interactions with specialized immune cells in vivo. The aim of the present study was to characterize the immune modulating properties of the food-related yeast Kluyveromyces marxianus in terms of adaptive immune responses indicating inflammation versus tolerance and to explore the mechanisms behind the observed responses. Benchmarking against a Saccharomyces boulardii strain with probiotic effects documented in clinical trials, we evaluated the ability of K. marxianus to modulate human dendritic cell (DC function in vitro. Further, we assessed yeast induced DC modulation of naive T cells toward effector responses dominated by secretion of IFNγ and IL-17 versus induction of a Treg response characterized by robust IL-10 secretion. In addition, we blocked relevant DC surface receptors and investigated the stimulating properties of β-glucan containing yeast cell wall extracts. K. marxianus and S. boulardii induced distinct levels of DC cytokine secretion, primarily driven by Dectin-1 recognition of β-glucan components in their cell walls. Upon co-incubation of yeast exposed DCs and naive T cells, S. boulardii induced a potent IFNγ response indicating TH1 mobilization. In contrast, K. marxianus induced a response dominated by Foxp3+ Treg cells, a characteristic that may benefit human health in conditions characterized by excessive inflammation and positions K. marxianus as a strong candidate for further development as a novel yeast probiotic.

  3. Kluyveromyces marxianus and Saccharomyces boulardii Induce Distinct Levels of Dendritic Cell Cytokine Secretion and Significantly Different T Cell Responses In Vitro.

    Science.gov (United States)

    Smith, Ida M; Baker, Adam; Christensen, Jeffrey E; Boekhout, Teun; Frøkiær, Hanne; Arneborg, Nils; Jespersen, Lene

    2016-01-01

    Interactions between members of the intestinal microbiota and the mucosal immune system can significantly impact human health, and in this context, fungi and food-related yeasts are known to influence intestinal inflammation through direct interactions with specialized immune cells in vivo. The aim of the present study was to characterize the immune modulating properties of the food-related yeast Kluyveromyces marxianus in terms of adaptive immune responses indicating inflammation versus tolerance and to explore the mechanisms behind the observed responses. Benchmarking against a Saccharomyces boulardii strain with probiotic effects documented in clinical trials, we evaluated the ability of K. marxianus to modulate human dendritic cell (DC) function in vitro. Further, we assessed yeast induced DC modulation of naive T cells toward effector responses dominated by secretion of IFNγ and IL-17 versus induction of a Treg response characterized by robust IL-10 secretion. In addition, we blocked relevant DC surface receptors and investigated the stimulating properties of β-glucan containing yeast cell wall extracts. K. marxianus and S. boulardii induced distinct levels of DC cytokine secretion, primarily driven by Dectin-1 recognition of β-glucan components in their cell walls. Upon co-incubation of yeast exposed DCs and naive T cells, S. boulardii induced a potent IFNγ response indicating TH1 mobilization. In contrast, K. marxianus induced a response dominated by Foxp3+ Treg cells, a characteristic that may benefit human health in conditions characterized by excessive inflammation and positions K. marxianus as a strong candidate for further development as a novel yeast probiotic.

  4. Development of ileal cytokine and immunoglobulin expression levels in response to early feeding in broilers and layers

    NARCIS (Netherlands)

    Simon, K.; Vries Reilingh, de G.; Kemp, B.; Lammers, A.

    2014-01-01

    Provision of feed in the immediate posthatch period may influence interaction between intestinal microbiota and immune system, and consequently immunological development of the chick. This study addressed ileal immune development in response to early feeding in 2 chicken breeds selected for

  5. Cytokine and matrix metalloproteinase expression in fibroblasts from peri-implantitis lesions in response to viable Porphyromonas gingivalis

    NARCIS (Netherlands)

    Irshad, M.; Scheres, N.; Anssari Moin, D.; Crielaard, W.; Loos, B.G.; Wismeijer, D.; Laine, M.L.

    2013-01-01

    Background and Objective To assess inflammatory reactions of fibroblasts in the pathophysiology of peri-implantitis, we compared the pro-inflammatory and matrix-degrading responses of gingival and granulation tissue fibroblasts from periodontally healthy controls, peri-implantitis, and periodontitis

  6. Enterococcus faecium NCIMB 10415 Modulates Epithelial Integrity, Heat Shock Protein, and Proinflammatory Cytokine Response in Intestinal Cells

    Directory of Open Access Journals (Sweden)

    Shanti Klingspor

    2015-01-01

    Full Text Available Probiotics have shown positive effects on gastrointestinal diseases; they have barrier-modulating effects and change the inflammatory response towards pathogens in studies in vitro. The aim of this investigation has been to examine the response of intestinal epithelial cells to Enterococcus faecium NCIMB 10415 (E. faecium, a probiotic positively affecting diarrhea incidence in piglets, and two pathogenic Escherichia coli (E. coli strains, with specific focus on the probiotic modulation of the response to the pathogenic challenge. Porcine (IPEC-J2 and human (Caco-2 intestinal cells were incubated without bacteria (control, with E. faecium, with enteropathogenic (EPEC or enterotoxigenic E. coli (ETEC each alone or in combination with E. faecium. The ETEC strain decreased transepithelial resistance (TER and increased IL-8 mRNA and protein expression in both cell lines compared with control cells, an effect that could be prevented by pre- and coincubation with E. faecium. Similar effects were observed for the increased expression of heat shock protein 70 in Caco-2 cells. When the cells were challenged by the EPEC strain, no such pattern of changes could be observed. The reduced decrease in TER and the reduction of the proinflammatory and stress response of enterocytes following pathogenic challenge indicate the protective effect of the probiotic.

  7. Proliferative responses of blood mononuclear cells (BMNC) in a cohort of elderly humans: role of lymphocyte phenotype and cytokine production

    DEFF Research Database (Denmark)

    Bruunsgaard, H.; Pedersen, Agnes Nadelmann; Schroll, M.

    2000-01-01

    Age-related impaired T cell function is associated with increased mortality risk. The purpose of the present study was therefore to identify factors associated with the age-related decreased phytohaemagglutinin (PHA)-induced proliferative response of lymphocytes in a cohort of 174 81-year...

  8. Polyfunctional cytokine production by central memory T cells from cattle in response to Mycobacterium bovis infection and BCG vaccination

    Science.gov (United States)

    Polyfunctional T cells simultaneously produce IFN-gamma, IL-2 and TNF-alpha and play relevant roles in several chronic infections, including TB. Mycobacterium bovis infection of cattle elicits ex vivo polyfunctional T cell responses. Vaccine-elicited IFN-gamma Tcm (CD4 plus CD45RO plus CCR7 plus) re...

  9. Combined chromatin and expression analysis reveals specific regulatory mechanisms within cytokine genes in the macrophage early immune response.

    Directory of Open Access Journals (Sweden)

    Maria Jesus Iglesias

    Full Text Available Macrophages play a critical role in innate immunity, and the expression of early response genes orchestrate much of the initial response of the immune system. Macrophages undergo extensive transcriptional reprogramming in response to inflammatory stimuli such as Lipopolysaccharide (LPS.To identify gene transcription regulation patterns involved in early innate immune responses, we used two genome-wide approaches--gene expression profiling and chromatin immunoprecipitation-sequencing (ChIP-seq analysis. We examined the effect of 2 hrs LPS stimulation on early gene expression and its relation to chromatin remodeling (H3 acetylation; H3Ac and promoter binding of Sp1 and RNA polymerase II phosphorylated at serine 5 (S5P RNAPII, which is a marker for transcriptional initiation. Our results indicate novel and alternative gene regulatory mechanisms for certain proinflammatory genes. We identified two groups of up-regulated inflammatory genes with respect to chromatin modification and promoter features. One group, including highly up-regulated genes such as tumor necrosis factor (TNF, was characterized by H3Ac, high CpG content and lack of TATA boxes. The second group, containing inflammatory mediators (interleukins and CCL chemokines, was up-regulated upon LPS stimulation despite lacking H3Ac in their annotated promoters, which were low in CpG content but did contain TATA boxes. Genome-wide analysis showed that few H3Ac peaks were unique to either +/-LPS condition. However, within these, an unpacking/expansion of already existing H3Ac peaks was observed upon LPS stimulation. In contrast, a significant proportion of S5P RNAPII peaks (approx 40% was unique to either condition. Furthermore, data indicated a large portion of previously unannotated TSSs, particularly in LPS-stimulated macrophages, where only 28% of unique S5P RNAPII peaks overlap annotated promoters. The regulation of the inflammatory response appears to occur in a very specific manner at

  10. Dairy cows produce cytokine and cytotoxic T cell responses following vaccination with an antigenic fraction from Streptococcus uberis.

    Science.gov (United States)

    Wedlock, D Neil; Buddle, Bryce M; Williamson, John; Lacy-Hulbert, S Jane; Turner, Sally-Anne; Subharat, Supatsak; Heiser, Axel

    2014-07-15

    Streptococcus uberis is a major cause of mastitis in dairy cows worldwide and currently, there is no vaccine commercially available against this form of mastitis. In the current study, cell-free extracts (CFE) were prepared from each of three different S. uberis strains, designated as #3, #24 and #363 representative of the three main sequence types of S. uberis that cause mastitis in New Zealand. These proteins were formulated into vaccines with Emulsigen-D and the immunogenicity of the vaccines was determined in both calves and dairy cows. Two groups of calves (n=5/group) were vaccinated subcutaneously with CFE from strain #24 or strains #3, #24 and #363 formulated with Emulsigen-D, respectively. A third group (n=5) was vaccinated with CFE from the three strains formulated with Emulsigen-D and also containing recombinant bovine granulocyte macrophage colony-stimulating factor while, a control group (n=5) was not vaccinated. Vaccinated animals produced strong antibody responses to the S. uberis antigens and an antigen-specific cytotoxic effect against blood monocytes/macrophages that had phagocytosed S. uberis, with no significant differences in responses observed between the three vaccinated groups. In a second trial, the safety and immunogenicity of the vaccine containing CFE from all three strains of S. uberis and Emulsigen-D was determined in dairy cows. A group of six cows were vaccinated subcutaneously at 3 and 1 week prior to dry off and revaccinated 2-3 weeks before calving. Immune responses in blood and mammary gland secretions (MGS) were monitored during the dry period and in the subsequent lactation. The vaccine was well tolerated with no adverse effect from vaccination observed in any of the cows. Vaccination induced an antigen-specific cytotoxic effect against blood monocytes/macrophages that had phagocytosed S. uberis, moderate antigen-specific IFN-γ responses in blood and strong antibody responses in both blood and MGS. In conclusion, the results

  11. Comparison of antibody and cytokine responses to primary Giardia muris infection in H-2 congenic strains of mice.

    Science.gov (United States)

    Venkatesan, P; Finch, R G; Wakelin, D

    1996-11-01

    The course of primary infections with Giardia muris differs between BALB and B10 H-2 congenic strains of mice. In the first 3 weeks of infection, there is a more rapid decline in intestinal trophozoite and fecal cyst counts in B10 strains than in BALB strains. To determine whether this difference could be explained by variation in specific antibody responses, both secretory immunoglobulin A (IgA) and serum antibody responses were compared between these strains. No significant differences in the timing, titer, or specificity of secretory or serum antibodies were found. However, on comparing specific anti-G. muris serum IgG subclass responses, we found that B10 strains produced IgG2a while BALB strains produced IgG1, suggesting differential involvement of T helper 1 and 2 subsets of lymphocytes. When cells harvested from mesenteric lymph nodes were stimulated with concanavalin A in vitro, both gamma interferon and interleukin-5 were secreted by cells from B10 mice, but only interleukin-5 was secreted by cells from BALB/c mice. Specific blockade of gamma interferon by monoclonal antibody administered to B10 mice resulted in an enhanced intensity of infection.

  12. Tissue responses to fractional transient heating with sinusoidal heat flux condition on skin surface.

    Science.gov (United States)

    Ezzat, Magdy A; El-Bary, Alaa A; Al-Sowayan, Noorah S

    2016-10-01

    A fractional model of Bioheat equation for describing quantitatively the thermal responses of skin tissue under sinusoidal heat flux conditions on skin surface is given. Laplace transform technique is used to obtain the solution in a closed form. The resulting formulation is applied to one-dimensional application to investigate the temperature distribution in skin with instantaneous surface heating for different cases. According to the numerical results and its graphs, conclusion about the fractional bioheat transfer equation has been constructed. Sensitivity analysis is performed to explore the thermal effects of various control parameters on tissue temperature. The comparisons are made with the results obtained in the case of the absence of time-fractional order. © 2016 Japanese Society of Animal Science. © 2016 Japanese Society of Animal Science.

  13. Cytokine profile of cervical cancer cells

    NARCIS (Netherlands)

    Hazelbag, S; Fleuren, GJ; Baelde, JJ; Schuuring, E; Kenter, GG; Gorter, A

    2001-01-01

    Objective. In patients with cervical carcinoma, the presence of cytokines produced by T(H)2 cells, and the presence of an eosinophilic inflammatory infiltrate, has been associated with a less effective immune response and tumor progression. In the present study, we have investigated the cytokine

  14. Cytokine profile of cervical cancer cells

    NARCIS (Netherlands)

    Hazelbag, S; Fleuren, GJ; Baelde, JJ; Schuuring, E; Kenter, GG; Gorter, A

    Objective. In patients with cervical carcinoma, the presence of cytokines produced by T(H)2 cells, and the presence of an eosinophilic inflammatory infiltrate, has been associated with a less effective immune response and tumor progression. In the present study, we have investigated the cytokine

  15. The Importance of Heating System Transient Response in Domestic Energy Labelling

    Directory of Open Access Journals (Sweden)

    George Bennett

    2016-08-01

    Full Text Available European National Calculation Methods (NCM, such as the UK Standard Assessment Procedure (SAP, are used to make standardised and simplified assessments of building energy performance. These NCMs contain simplifications to aid ease of use and comparability of resulting Energy Performance Certificates (EPC. By comparing SAP with a modern, dynamic modelling system, this study quantifies internal temperatures and thereby heating energy consumption. Results show that for the considered test house SAP results correspond closely to a dynamic model using an idealistic heating system, with perfect control and instant responsiveness. However, the introduction of a dynamic, physically realistic gas fired boiler and water based heating system to the model results in a consistent increase in internal temperature (0.5 °C and energy demand (by ca. 1000 kWh/a. Variation of further parameters within the dynamic model, controls and heat source size, are presented and compared to SAP results and assumptions. The inclusion of more realistic dynamics in building energy modelling for NCMs may provide a better basis for effective decision making with respect to a wide range of heating systems.

  16. Thermal Response of Tritiated Codeposits from JET and TFTR to Transient Heat Pulses

    International Nuclear Information System (INIS)

    Skinner, C.H.; Bekrisl, N.; Coad, J.P.; Gentile, C.A.; Hassanein, A.; Reiswig, R.; Willms, S.

    2002-01-01

    High heat flux interactions with plasma-facing components have been studied at microscopic scales. The beam from a continuous wave neodymium laser was scanned at high speed over the surface of graphite and carbon fiber composite tiles that had been retrieved from TFTR (Tokamak Fusion Test Reactor) and JET (Joint European Torus) after D-T plasma operations. The tiles have a surface layer of amorphous hydrogenated carbon that was co-deposited during plasma operations, and laser scanning has released more than 80% of the co-deposited tritium. The temperature rise of the co-deposit was much higher than that of the manufactured material and showed an extended time history. The peak temperature varied dramatically (e.g., 1,436 C compared to >2,300 C), indicating strong variations in the thermal conductivity to the substrate. A digital microscope imaged the co-deposit before, during, and after the interaction with the laser and revealed 100-micron scale hot spots during the interaction. Heat pulse durations of order 100 ms resulted in brittle destruction and material loss from the surface, whilst a duration of =10 ms showed minimal changes to the co-deposit. These results show that reliable predictions for the response of deposition areas to off-normal events such as ELMs (edge-localized modes) and disruptions in next-step devices need to be based on experiments with tokamak generated co-deposits

  17. A dynamic-biased dual-loop-feedback CMOS LDO regulator with fast transient response

    International Nuclear Information System (INIS)

    Wang Han; Sun Maomao

    2014-01-01

    This paper presents a low-dropout regulator (LDO) for portable applications with dual-loop feedback and a dynamic bias circuit. The dual-loop feedback structure is adopted to reduce the output voltage spike and the response time of the LDO. The dynamic bias circuit enhances the slew rate at the gate of the power transistor. In addition, an adaptive miller compensation technique is employed, from which a single pole system is realized and over a 59° phase margin is achieved under the full range of the load current. The proposed LDO has been implemented in a 0.6-μm CMOS process. From the experimental results, the regulator can operate with a minimum dropout voltage of 200 mV at a maximum 300 mA load and I Q of 113 μA. The line regulation and load regulation are improved to 0.1 mV/V and 3.4 μV/mA due to the sufficient loop gain provided by the dual feedback loops. Under a full range load current step, the voltage spikes and the recovery time of the proposed LDO is reduced to 97 mV and 0.142 μs respectively. (semiconductor integrated circuits)

  18. Analysis of the transient response of LED-illuminated diodes under heavy radiation damage

    CERN Document Server

    Passeri, D; Bilei, G M; Casse, G L; Lemeilleur, F

    2000-01-01

    The changes of the electrical properties induced by hadron irradiation on silicon detectors have been studied by using the device level simulator HFIELDS. The model of the radiation damage assumes the introduction of radiation-induced acceptor and donor "deep-levels". The electric field profile and the space charge region extension have been calculated for differently irradiated structures. The simulation has been carried out at different biases in order to study the evolution of the space charge region of irradiated detectors as a function of the applied voltages, below and above the full depletion. The time-dependent current responses and the charge collection properties of the structure illuminated by a red LED light have been calculated. The use of the red light results in a shallow (quasi-surface) generation of e-h pairs in silicon, which has been properly taken into account by the simulation. The results of the simulations have been compared to experimental measurements carried out at CERN on samples ir...

  19. Functional difference between sustained and transient modulations of cognitive control in the simon task: evidence from false alarm responses on no-go trials.

    Science.gov (United States)

    Hasegawa, Kunihiro; Takahashi, Shin'ya

    2013-01-01

    Cognitive control in response compatibility tasks is modulated by the task context. Two types of contextual modulations have been demonstrated; sustained (block-wise) and transient (trial-by-trial). Recent research suggests that these modulations have different underlying mechanisms. This study presents new evidence supporting this claim by comparing false alarm (FA) responses on no-go trials of the Simon task between the sustained and transient contexts. In Experiment 1, the sustained context was manipulated so that a block included a larger number of incongruent trials. Results showed that participants made more FA responses by the hand opposite to the stimulus location. This suggests a generation of response bias in which the task-irrelevant location information is utilized in a reversed manner (i.e., to respond with the right hand to a stimulus presented on the left side and vice versa). Next, Experiment 2 examined the effect of the transient context and found that overall FA rate was lower when a no-go trial was preceded by an incongruent trial than by a congruent trial, whereas such response bias as that shown in Experiment 1 was not demonstrated. This suggests that the transient conflict context enhances inhibition of the task-irrelevant process but does not make the task-irrelevant information actively usable. Based on these results, we propound two types of cognitive control modulations as adaptive behaviors: response biasing based on utilization of the task-irrelevant information under the sustained conflict context and transient enhancement of inhibition of the task-irrelevant process based on the online conflict monitoring.

  20. MiR-155 induction by F. novicida but not the virulent F. tularensis results in SHIP down-regulation and enhanced pro-inflammatory cytokine response.

    Directory of Open Access Journals (Sweden)

    Thomas J Cremer

    2009-12-01

    Full Text Available The intracellular gram-negative bacterium Francisella tularensis causes the disease tularemia and is known for its ability to subvert host immune responses. Previous work from our laboratory identified the PI3K/Akt pathway and SHIP as critical modulators of host resistance to Francisella. Here, we show that SHIP expression is strongly down-regulated in monocytes and macrophages following infection with F. tularensis novicida (F.n.. To account for this negative regulation we explored the possibility that microRNAs (miRs that target SHIP may be induced during infection. There is one miR that is predicted to target SHIP, miR-155. We tested for induction and found that F.n. induced miR-155 both in primary monocytes/macrophages and in vivo. Using luciferase reporter assays we confirmed that miR-155 led to down-regulation of SHIP, showing that it specifically targets the SHIP 3'UTR. Further experiments showed that miR-155 and BIC, the gene that encodes miR-155, were induced as early as four hours post-infection in primary human monocytes. This expression was dependent on TLR2/MyD88 and did not require inflammasome activation. Importantly, miR-155 positively regulated pro-inflammatory cytokine release in human monocytes infected with Francisella. In sharp contrast, we found that the highly virulent type A SCHU S4 strain of Francisella tularensis (F.t. led to a significantly lower miR-155 response than the less virulent F.n. Hence, F.n. induces miR-155 expression and leads to down-regulation of SHIP, resulting in enhanced pro-inflammatory responses. However, impaired miR-155 induction by SCHU S4 may help explain the lack of both SHIP down-regulation and pro-inflammatory response and may account for the virulence of Type A Francisella.

  1. Nanovesicles from Malassezia sympodialis and host exosomes induce cytokine responses--novel mechanisms for host-microbe interactions in atopic eczema.

    Directory of Open Access Journals (Sweden)

    Ulf Gehrmann

    Full Text Available BACKGROUND: Intercellular communication can occur via the release of membrane vesicles. Exosomes are nanovesicles released from the endosomal compartment of cells. Depending on their cell of origin and their cargo they can exert different immunoregulatory functions. Recently, fungi were found to produce extracellular vesicles that can influence host-microbe interactions. The yeast Malassezia sympodialis which belongs to our normal cutaneous microbial flora elicits specific IgE- and T-cell reactivity in approximately 50% of adult patients with atopic eczema (AE. Whether exosomes or other vesicles contribute to the inflammation has not yet been investigated. OBJECTIVE: To investigate if M. sympodialis can release nanovesicles and whether they or endogenous exosomes can activate PBMC from AE patients sensitized to M. sympodialis. METHODS: Extracellular nanovesicles isolated from M. sympodialis, co-cultures of M. sympodialis and dendritic cells, and from plasma of patients with AE and healthy controls (HC were characterised using flow cytometry, sucrose gradient centrifugation, Western blot and electron microscopy. Their ability to stimulate IL-4 and TNF-alpha responses in autologous CD14, CD34 depleted PBMC was determined using ELISPOT and ELISA, respectively. RESULTS: We show for the first time that M. sympodialis releases extracellular vesicles carrying allergen. These vesicles can induce IL-4 and TNF-α responses with a significantly higher IL-4 production in patients compared to HC. Exosomes from dendritic cell and M. sympodialis co-cultures induced IL-4 and TNF-α responses in autologous CD14, CD34 depleted PBMC of AE patients and HC while plasma exosomes induced TNF-α but not IL-4 in undepleted PBMC. CONCLUSIONS: Extracellular vesicles from M. sympodialis, dendritic cells and plasma can contribute to cytokine responses in CD14, CD34 depleted and undepleted PBMC of AE patients and HC. These novel observations have implications for

  2. Lack of Proinflammatory Cytokine Interleukin-6 or Tumor Necrosis Factor Receptor-1 Results in a Failure of the Innate Immune Response after Bacterial Meningitis

    Directory of Open Access Journals (Sweden)

    Lea-Jessica Albrecht

    2016-01-01

    Full Text Available The most frequent pathogen that causes bacterial meningitis is the Gram-positive bacterium Streptococcus pneumoniae. By entering the brain, host cells will be activated and proinflammatory cytokines like interleukin-6 (IL-6 and tumor necrosis factor-α (TNF-α are released. The goal of the current study was to examine the interaction between IL-6 and TNFR1 as receptor for TNF-α and the innate immune response in vivo in a model of Streptococcus pneumoniae-induced meningitis. For the experiments IL-6−/−, TNFR1−/−, and TNFR1-IL-6−/− KO mice were used. Our results revealed higher mortality rates and bacterial burden after infection in TNFR1−/−, IL-6−/−, and TNFR1-IL-6−/− mice and a decreased immune response including lower neutrophil infiltration in the meninges of TNFR1−/− and TNFR1-IL-6−/− mice in contrast to IL-6−/− and wild type mice. Furthermore, the increased mortality of TNFR1−/− and TNFR1-IL-6−/− mice correlated with decreased glial cell activation compared to IL-6−/− or wild type mice after pneumococcal meningitis. Altogether, the results show the importance of TNFR1 and IL-6 in the regulation of the innate immune response. The lack of TNFR1 and IL-6 results in higher mortality by weakened immune defence, whereas the lack of TNFR1 results in more severe impairment of the innate immune response than the lack of IL-6 alone.

  3. Expert judgments about transient climate response to alternative future trajectories of radiative forcing.

    Science.gov (United States)

    Zickfeld, Kirsten; Morgan, M Granger; Frame, David J; Keith, David W

    2010-07-13

    There is uncertainty about the response of the climate system to future trajectories of radiative forcing. To quantify this uncertainty we conducted face-to-face interviews with 14 leading climate scientists, using formal methods of expert elicitation. We structured the interviews around three scenarios of radiative forcing stabilizing at different levels. All experts ranked "cloud radiative feedbacks" as contributing most to their uncertainty about future global mean temperature change, irrespective of the specified level of radiative forcing. The experts disagreed about the relative contribution of other physical processes to their uncertainty about future temperature change. For a forcing trajectory that stabilized at 7 Wm(-2) in 2200, 13 of the 14 experts judged the probability that the climate system would undergo, or be irrevocably committed to, a "basic state change" as > or =0.5. The width and median values of the probability distributions elicited from the different experts for future global mean temperature change under the specified forcing trajectories vary considerably. Even for a moderate increase in forcing by the year 2050, the medians of the elicited distributions of temperature change relative to 2000 range from 0.8-1.8 degrees C, and some of the interquartile ranges do not overlap. Ten of the 14 experts estimated that the probability that equilibrium climate sensitivity exceeds 4.5 degrees C is > 0.17, our interpretation of the upper limit of the "likely" range given by the Intergovernmental Panel on Climate Change. Finally, most experts anticipated that over the next 20 years research will be able to achieve only modest reductions in their degree of uncertainty.

  4. Cytokine response to selected MTB antigens in Ghanaian TB patients, before and at 2 weeks of anti-TB therapy is characterized by high expression of IFN-γ and Granzyme B and inter- individual variation.

    Science.gov (United States)

    Mensah, Gloria Ivy; Addo, Kennedy Kwasi; Tetteh, John Amissah; Sowah, Sandra; Loescher, Thomas; Geldmacher, Christof; Jackson-Sillah, Dolly

    2014-09-10

    There has been a long held belief that patients with drug-susceptible TB are non-infectious after two weeks of therapy. Recent microbiological and epidemiological evidence has challenged this dogma, however, the nature of the Mtb-specific cellular immune response during this period has not been adequately investigated. This knowledge could be exploited in the development of immunological biomarkers of early treatment response. Cellular response to four Mtb infection phase-dependent antigens, ESAT-6/CFP-10 fusion protein and three DosR encoded proteins (Rv1733c, Rv2029c, Rv2628) were evaluated in a Ghanaian TB cohort (n=20) before and after 2 weeks of anti TB therapy. After 6-days in vitro stimulation, Peripheral blood mononuclear cell (PBMC) culture supernatant was harvested and the concentration of IFN-γ, Granzyme B, IL-10, IL-17, sIL2Rα and TNF-α were determined in a 6-plex Luminex assay. Frequencies of IFN-γ + CD4 and CD8 T cells were also determined in an intracellular cytokine assay. All antigens induced higher levels of IFN-γ, followed by Granzyme B, TNF-α and IL-17 and low levels of IL-10 and sIL-2R-α in PBMC before treatment and after 2 weeks of treatment. Median cytokine levels of IFN-γ, Granzyme B, IL-17 and sIL-2R-α increased during week two, but it was significant for only Rv1733-specific production of Granzyme B (P = 0. 013). The median frequency of antigen specific IFN-γ + CD4 T cells increased at week two; however, only the increase in the ESAT-6/CFP-10-specific response was significant (P = 0. 0008). In contrast, the median frequency of ESAT-6/CFP-10- specific IFN-γ + CD8 T cell responses declined during week two (P = 0. 0024). Additionally, wide inter-individual variation with three distinct patterns were observed; increase in all cytokine levels, decrease in all cytokine levels and fluctuating cytokine levels after 2 weeks of treatment. The second week of effective chemotherapy was characterized by a general increase in cytokine

  5. Effect of cytokine-encoding plasmid delivery on immune response to Japanese encephalitis virus DNA vaccine in mice.

    Science.gov (United States)

    Bharati, Kaushik; Appaiahgari, Mohan Babu; Vrati, Sudhanshu

    2005-01-01

    We have previously shown that immunization of mice with plasmid pMEa synthesizing Japanese encephalitis virus (JEV) envelope protein induced anti-JEV humoral and cellular immune responses. We now show that intra-muscular co-administration of mice with pMEa and pGM-CSF, encoding murine granulocyte-macrophage colony-stimulating factor or pIL-2, encoding murine interleukin-2 given 4 days after pMEa, augmented anti-JEV antibody titers. This did not enhance the level of protection in immunized mice against JEV. However, intra-dermal co-administration of pMEa and pGM-CSF in mice using the gene gun, enhanced anti-JEV antibody titers resulting in an increased level of protection in mice against lethal JEV challenge.

  6. Maysin and Its Flavonoid Derivative from Centipedegrass Attenuates Amyloid Plaques by Inducting Humoral Immune Response with Th2 Skewed Cytokine Response in the Tg (APPswe, PS1dE9 Alzheimer's Mouse Model.

    Directory of Open Access Journals (Sweden)

    Yuno Song

    Full Text Available Alzheimer's disease (AD is a slow, progressive neurodegenerative disease and the most common type of dementia in the elderly. The etiology of AD and its underlying mechanism are still not clear. In a previous study, we found that an ethyl acetate extract of Centipedegrass (CG (i.e., EA-CG contained 4 types of Maysin derivatives, including Luteolin, Isoorientin, Rhamnosylisoorientin, and Derhamnosylmaysin, and showed protective effects against Amyloid beta (Aβ by inhibiting oligomeric Aβ in cellular and in vitro models. Here, we examined the preventative effects of EA-CG treatment on the Aβ burden in the Tg (Mo/Hu APPswe PS1dE9 AD mouse model. We have investigated the EA-CG efficacy as novel anti-AD likely preventing amyloid plaques using immunofluorescence staining to visually analyze Aβ40/42 and fibril formation with Thioflavin-S or 6E10 which are the profile of immunoreactivity against epitope Aβ1-16 or neuritic plaque, the quantitation of humoral immune response against Aβ, and the inflammatory cytokine responses (Th1 and Th2 using ELISA and QRT-PCR. To minimize the toxicity of the extracted CG, we addressed the liver toxicity in response to the CG extract treatment in Tg mice using relevant markers, such as aspartate aminotransferase (AST/ alanine aminotransferase (ALT measurements in serum. The EA-CG extract significantly reduced the Aβ burden, the concentration of soluble Aβ40/42 protein, and fibril formation in the hippocampus and cortex of the Tg mice treated with EA-CG (50 mg/kg BW/day for 6 months compared with the Tg mice treated with a normal diet. Additionally, the profile of anti-inflammatory cytokines revealed that the levels of Th2 (interleukin-4 (IL-4 and interleukin-10 (IL-10 cytokines are more significantly increased than Th1 (interferon-γ (IFN-γ, interleukin-2(IL-2 in the sera. These results suggest that the EA-CG fraction induces IL-4/IL-10-dependent anti-inflammatory cytokines (Th2 rather than pro

  7. The Local Inflammatory Responses to Infection of the Peritoneal Cavity in Humans: Their Regulation by Cytokines, Macrophages, and Other Leukocytes

    Directory of Open Access Journals (Sweden)

    Marien Willem Johan Adriaan Fieren

    2012-01-01

    Full Text Available Studies on infection-induced inflammatory reactions in humans rely largely on findings in the blood compartment. Peritoneal leukocytes from patients treated with peritoneal dialysis offer a unique opportunity to study in humans the inflammatory responses taking place at the site of infection. Compared with peritoneal macrophages (pM from uninfected patients, pM from infected patients display ex vivo an upregulation and downregulation of proinflammatory and anti-inflammatory mediators, respectively. Pro-IL-1 processing and secretion rather than synthesis proves to be increased in pM from infectious peritonitis suggesting up-regulation of caspase-1 in vivo. A crosstalk between pM, γ T cells, and neutrophils has been found to be involved in augmented TNF expression and production during infection. The recent finding in experimental studies that alternatively activated macrophages (M2 increase by proliferation rather than recruitment may have significant implications for the understanding and treatment of chronic inflammatory conditions such as encapsulating peritoneal sclerosis (EPS.

  8. Resistive wall mode feedback control in EXTRAP T2R with improved steady-state error and transient response

    Science.gov (United States)

    Brunsell, P. R.; Olofsson, K. E. J.; Frassinetti, L.; Drake, J. R.

    2007-10-01

    Experiments in the EXTRAP T2R reversed field pinch [P. R. Brunsell, H. Bergsåker, M. Cecconello et al., Plasma Phys. Control. Fusion 43, 1457 (2001)] on feedback control of m =1 resistive wall modes (RWMs) are compared with simulations using the cylindrical linear magnetohydrodynamic model, including the dynamics of the active coils and power amplifiers. Stabilization of the main RWMs (n=-11,-10,-9,-8,+5,+6) is shown using modest loop gains of the order G ˜1. However, other marginally unstable RWMs (n=-2,-1,+1,+2) driven by external field errors are only partially canceled at these gains. The experimental system stability limit is confirmed by simulations showing that the latency of the digital controller ˜50μs is degrading the system gain margin. The transient response is improved with a proportional-plus-derivative controller, and steady-state error is improved with a proportional-plus-integral controller. Suppression of all modes is obtained at high gain G ˜10 using a proportional-plus-integral-plus-derivative controller.

  9. Understanding chemical-potential-related transient pore-pressure response to improve real-time borehole (in)stability predictions

    Energy Technology Data Exchange (ETDEWEB)

    Tare, U.A.; Mody, F.K.; Mese, A.I. [Halliburton Energy Services, Cairo (Egypt)

    2000-11-01

    Experimental studies were conducted to explain the concept of a real-time wellbore (in)stability logging methodology. The role of the chemical potential of drilling fluids on transient pore pressure and time-dependent rock property alterations of shale formations was examined by providing details about a pore pressure transmission (PPT) test. The PPT experiments exposed formation (shale) cores under simulated downhole conditions to various salt solutions and drilling fluids. The main objective was to translate the results of the PPT tests to actual drilling conditions. A 20 per cent w/w calcium chloride solution was exposed to a Pierre II shale under high pressure in the PPT apparatus. The PPT test was used to estimate the impact of a drilling fluid on shale pore pressure. The efficiency of the salt solution/shale system was also estimated. Estimates of the dynamic rock properties were made based on the obtained acoustic data. It was determined that in order to accurately model time-dependent wellbore (in)stability in the field, it is important to calibrate representative shale core response to drilling fluids under realistic in-situ conditions. The 20 per cent w/w calcium chloride solution showed very low membrane efficiency of 4.45 per cent. It was concluded that changes in the shale dynamic rock properties as a function of test fluid exposure can be obtained from the simultaneous acquisition of sonic compression and shear wave velocity data. 12 refs., 5 figs.

  10. Determination of charge transfer resistance and capacitance of microbial fuel cell through a transient response analysis of cell voltage.

    Science.gov (United States)

    Ha, Phuc Thi; Moon, Hyunsoo; Kim, Byung Hong; Ng, How Yong; Chang, In Seop

    2010-03-15

    An alternative method for determining the charge transfer resistance and double-layer capacitance of microbial fuel cells (MFCs), easily implemented without a potentiostat, was developed. A dynamic model with two parameters, the charge transfer resistance and double-layer capacitance of electrodes, was derived from a linear differential equation to depict the current generation with respect to activation overvoltage. This model was then used to fit the transient cell voltage response to the current step change during the continuous operation of a flat-plate type MFC fed with acetate. Variations of the charge transfer resistance and the capacitance value with respect to the MFC design conditions (biocatalyst existence and electrode area) and operating parameters (acetate concentration and buffer strength in the catholyte) were then determined to elucidate the validity of the proposed method. This model was able to describe the dynamic behavior of the MFC during current change in the activation loss region; having an R(2) value of over 0.99 in most tests. Variations of the charge transfer resistance value (thousands of Omega) according to the change of the design factors and operational factors were well-correlated with the corresponding MFC performances. However, though the capacitance values (approximately 0.02 F) reflected the expected trend according to the electrode area change and catalyst property, they did not show significant variation with changes in either the acetate concentration or buffer strength. (c) 2009 Elsevier B.V. All rights reserved.

  11. LOFT/LP-FW-1, Loss of Fluid Test, PWR Response to Loss-of-Feedwater Transient

    International Nuclear Information System (INIS)

    1989-01-01

    1 - Description of test facility: The LOFT Integral Test Facility is a scale model of a LPWR. The intent of the facility is to model the nuclear, thermal-hydraulic phenomena which would take place in a LPWR during a LOCA. The general philosophy in scaling coolant volumes and flow areas in LOFT was to use the ratio of the LOFT core [50 MW(t)] to a typical LPWR core [3000 MW(t)]. For some components, this factor is not applied; however, it is used as extensively as practical. In general, components used in LOFT are similar in design to those of a LPWR. Because of scaling and component design, the LOFT LOCA is expected to closely model a LPWR LOCA. 2 - Description of test: The first OECD LOFT experiment was conducted on February 20, 1983. It was designed to evaluate the generic PWR system response during a complete loss-of-feedwater transient. The objective of the experiment was to investigate the performance of primary 'feed and bleed' using a 'bleed' from the PORV and 'feed' from the HPIS to provide decay heat removal and system pressure reduction while maintaining the primary coolant inventory. 3 - Experimental limitations or shortcomings: Short core and steam generator, excessive core bypass, other scaling compromises, and lack of adequate measurements in certain areas

  12. A 3 A sink/source current fast transient response low-dropout G{sub m} driven linear regulator

    Energy Technology Data Exchange (ETDEWEB)

    Chu Xiuqin; Li Qingwei; Lai Xinquan; Yuan Bing [Institute of Electronic CAD, Xidian University, Xi' an 710071 (China); Li Yanming [School of Electronic and Control Engineering, Chang' an University, Xi' an 710064 (China); Zhao Yongrui, E-mail: liqw309@163.com, E-mail: xqchu@mail.xidian.edu.cn [Key Laboratory of High-Speed Circuit Design and EMC, Ministry of Education, Xidian University, Xi' an 710071 (China)

    2011-06-15

    A 3 A sink/source G{sub m}-driven CMOS low-dropout regulator (LDO), specially designed for low input voltage and low cost, is presented by utilizing the structure of a current mirror G{sub m} (transconductance) driving technique, which provides high stability as well as a fast load transient response. The proposed LDO was fabricated by a 0.5 {mu}m standard CMOS process, and the die size is as small as 1.0 mm{sup 2}. The proposed LDO dissipates 220 {mu}A of quiescent current in no-load conditions and is able to deliver up to 3 A of load current. The measured results show that the output voltage can be resumed within 2 {mu}s with a less than 1 mV overshoot and undershoot in the output current step from -1.8 to 1.8 A with a 0.1 {mu}s rising and falling time at three 10 {mu}F ceramic capacitors. (semiconductor integrated circuits)

  13. A 3 A sink/source current fast transient response low-dropout Gm driven linear regulator

    International Nuclear Information System (INIS)

    Chu Xiuqin; Li Qingwei; Lai Xinquan; Yuan Bing; Li Yanming; Zhao Yongrui

    2011-01-01

    A 3 A sink/source G m -driven CMOS low-dropout regulator (LDO), specially designed for low input voltage and low cost, is presented by utilizing the structure of a current mirror G m (transconductance) driving technique, which provides high stability as well as a fast load transient response. The proposed LDO was fabricated by a 0.5 μm standard CMOS process, and the die size is as small as 1.0 mm 2 . The proposed LDO dissipates 220 μA of quiescent current in no-load conditions and is able to deliver up to 3 A of load current. The measured results show that the output voltage can be resumed within 2 μs with a less than 1 mV overshoot and undershoot in the output current step from -1.8 to 1.8 A with a 0.1 μs rising and falling time at three 10 μF ceramic capacitors. (semiconductor integrated circuits)

  14. Time-Domain Three Dimensional BE-FE Method for Transient Response of Floating Structures Under Unsteady Loads

    Directory of Open Access Journals (Sweden)

    R. E. S. Ismail

    Full Text Available Abstract This paper presents a direct time-domain three dimensional (3D numerical procedure to simulate the transient response of very large floating structures (VLFS subjected to unsteady external loads as well as moving mass. The proposed procedure employs the Boundary Element and Finite Element methods (FEM-BEM. The floating structure and the surrounding fluid are discretized by 4-node isoparametric finite elements (FE and by 4-node constant boundary elements (BE, respectively. Structural analysis is based on Mindlin's plate theory. The equation of motion is constructed taking into account the effect of inertia loading due to the moving mass. In order to obtain the hydrodynamic forces (added mass and radiation damping, the coupled natural frequencies are first obtained by an iterative method, since hydrodynamic forces become frequency-dependent. Then the Newark integration method is employed to solve the equation of motion for structural system. In order to prove the validity of the present method, a FORTRAN program is developed and numerical examples are carried out to compare its results with those of published experimental results of a scale model of VLFS under a weight drop and airplane landing and takeoff in still water condition. The comparisons show very good agreement.

  15. Temporal Patterns in Sheep Fetal Heart Rate Variability Correlate to Systemic Cytokine Inflammatory Response: A Methodological Exploration of Monitoring Potential Using Complex Signals Bioinformatics.

    Directory of Open Access Journals (Sweden)

    Christophe L Herry

    Full Text Available Fetal inflammation is associated with increased risk for postnatal organ injuries. No means of early detection exist. We hypothesized that systemic fetal inflammation leads to distinct alterations of fetal heart rate variability (fHRV. We tested this hypothesis deploying a novel series of approaches from complex signals bioinformatics. In chronically instrumented near-term fetal sheep, we induced an inflammatory response with lipopolysaccharide (LPS injected intravenously (n = 10 observing it over 54 hours; seven additional fetuses served as controls. Fifty-one fHRV measures were determined continuously every 5 minutes using Continuous Individualized Multi-organ Variability Analysis (CIMVA. CIMVA creates an fHRV measures matrix across five signal-analytical domains, thus describing complementary properties of fHRV. We implemented, validated and tested methodology to obtain a subset of CIMVA fHRV measures that matched best the temporal profile of the inflammatory cytokine IL-6. In the LPS group, IL-6 peaked at 3 hours. For the LPS, but not control group, a sharp increase in standardized difference in variability with respect to baseline levels was observed between 3 h and 6 h abating to baseline levels, thus tracking closely the IL-6 inflammatory profile. We derived fHRV inflammatory index (FII consisting of 15 fHRV measures reflecting the fetal inflammatory response with prediction accuracy of 90%. Hierarchical clustering validated the selection of 14 out of 15 fHRV measures comprising FII. We developed methodology to identify a distinctive subset of fHRV measures that tracks inflammation over time. The broader potential of this bioinformatics approach is discussed to detect physiological responses encoded in HRV measures.

  16. Natural killer cell cytokine response to M. bovis BCG Is associated with inhibited proliferation, increased apoptosis and ultimate depletion of NKp44(+CD56(bright cells.

    Directory of Open Access Journals (Sweden)

    Damien Portevin

    Full Text Available Mycobacterium bovis BCG, a live attenuated strain of M. bovis initially developed as a vaccine against tuberculosis, is also used as an adjuvant for immunotherapy of cancers and for treatment of parasitic infections. The underlying mechanisms are thought to rely on its immunomodulatory properties including the recruitment of natural killer (NK cells. In that context, we aimed to study the impact of M. bovis BCG on NK cell functions. We looked at cytotoxicity, cytokine production, proliferation and cell survival of purified human NK cells following exposure to single live particles of mycobacteria. We found that M. bovis BCG mediates apoptosis of NK cells only in the context of IL-2 stimulation during which CD56(bright NK cells are releasing IFN-γ in response to mycobacteria. We found that the presence of mycobacteria prevented the IL-2 induced proliferation and surface expression of NKp44 receptor by the CD56(bright population. In summary, we observed that M. bovis BCG is modulating the functions of CD56(bright NK cells to drive this subset to produce IFN-γ before subsequent programmed cell death. Therefore, IFN-γ production by CD56(bright cells constitutes the main effector mechanism of NK cells that would contribute to the benefits observed for M. bovis BCG as an immunotherapeutic agent.

  17. Electrical coupling suppression and transient response improvement for a microgyroscope using ascending frequency drive with a 2-DOF PID controller

    International Nuclear Information System (INIS)

    Cui, J; Guo, Z Y; Yang, Z C; Hao, Y L; Yan, G Z

    2011-01-01

    In this paper, we demonstrate a novel control strategy for the drive mode of a microgyroscope using ascending frequency drive (AFD) with an AGC-2DOF PID controller, which drives a resonator with a modulation signal not at the resonant frequency and senses the vibration signal at the resonant frequency, thus realizing the isolation between the actual mechanical response and electrical coupling signal. This approach holds the following three advantages: (1) it employs the AFD signal instead of the resonant frequency drive signal to excite the gyroscope in the drive direction, suppressing the electrical coupling from the drive electrode to the sense electrode; (2) it can reduce the noise at low frequency and resonant frequency by shifting flicker noise to the high-frequency part; (3) it can effectively improve the performance of the transient response of the closed-loop control with a 2-DOF (degree of freedom) PID controller compared with the conventional 1-DOF PID. The stability condition of the whole loop is investigated by utilizing the averaging and linearization method. The control approach is applied to drive a lateral tuning fork microgyroscope. Test results show good agreement with the theoretical and simulation results. The non-ideal electrical antiresonance peak is removed and the resonant peak height increases by approximately 10 dB over a 400 Hz span with a flicker noise reduction of 30 dB within 100 Hz using AFD. The percent overshoot is reduced from 36.2% (1DOF PID) to 8.95% (2DOF PID, about 75.3% overshoot suppression) with 15.3% improvement in setting time

  18. Modeling and analysis of thermal-hydraulic response of uranium-aluminum reactor fuel plates under transient heatup conditions

    Energy Technology Data Exchange (ETDEWEB)

    Navarro-Valenti, S.; Kim, S.H.; Georgevich, V. [Oak Ridge National Lab., TN (United States)] [and others

    1995-09-01

    The purpose of this paper is to describe the analysis performed to predict the thermal behavior of fuel miniplates under rapid transient heatup conditions. The possibility of explosive boiling was considered, and it was concluded that the heating rates are not large enough for explosive boiling to occur. However, transient boiling effects were pronounced. Because of the complexity of transient pool boiling and the unavailability of experimental data for the situations studied, an approximation was made that predicted the data very well within the uncertainties present. If pool boiling from the miniplates had been assumed to be steady during the heating pulse, the experimental data would have been greatly overestimated. This fact demonstrates the importance of considering the transient nature of heat transfer in the analysis of reactivity excursion accidents. An additional contribution of the present work is that it provided data on highly subcooled steady nulceate boiling from the cooling portion of the thermocouple traces.

  19. Cytokine responses of CD4+ T cells during a Plasmodium chabaudi chabaudi (ER blood-stage infection in mice initiated by the natural route of infection

    Directory of Open Access Journals (Sweden)

    Butcher Geoffrey

    2007-06-01

    Full Text Available Abstract Background Investigation of host responses to blood stages of Plasmodium spp, and the immunopathology associated with this phase of the life cycle are often performed on mice infected directly with infected red blood cells. Thus, the effects of mosquito bites and the pre-erythrocytic stages of the parasite, which would be present in natural infection, are ignored In this paper, Plasmodium chabaudi chabaudi infections of mice injected directly with infected red blood cells were compared with those of mice infected by the bites of infected mosquitoes, in order to determine whether the courses of primary infection and splenic CD4 T cell responses are similar. Methods C57Bl/6 mice were injected with red blood cells infected with P. chabaudi (ER or infected via the bite of Anopheles stephensi mosquitoes. Parasitaemia were monitored by Giemsa-stained thin blood films. Total spleen cells, CD4+ T cells, and cytokine production (IFN-γ, IL-2, IL-4, IL-10 were analysed by flow cytometry. In some experiments, mice were subjected to bites of uninfected mosquitoes prior to infectious bites in order to determine whether mosquito bites per se could affect a subsequent P. chabaudi infection. Results P. chabaudi (ER infections initiated by mosquito bite were characterized by lower parasitaemia of shorter duration than those observed after direct blood challenge. However, splenomegaly was comparable suggesting that parasitaemia alone does not account for the increase in spleen size. Total numbers of CD4 T cells and those producing IFN-γ, IL-10 and IL-2 were reduced in comparison to direct blood challenge. By contrast, the reduction in IL-4 producing cells was less marked suggesting that there is a proportionally lower Th1-like response in mice infected via infectious mosquitoes. Strikingly, pre-exposure to bites of uninfected mosquitoes reduced the magnitude and duration of the subsequent mosquito-transmitted infection still further, but enhanced the

  20. Threonine modulates immune response, antioxidant status and gene expressions of antioxidant enzymes and antioxidant-immune-cytokine-related signaling molecules in juvenile blunt snout bream (Megalobrama amblycephala).

    Science.gov (United States)

    Habte-Tsion, Habte-Michael; Ren, Mingchun; Liu, Bo; Ge, Xianping; Xie, Jun; Chen, Ruli

    2016-04-01

    A 9-week feeding trial was conducted to investigate the effects of graded dietary threonine (Thr) levels (0.58-2.58%) on the hematological parameters, immune response, antioxidant status and hepatopancreatic gene expression of antioxidant enzymes and antioxidant-immune-cytokine-related signaling molecules in juvenile blunt snout bream. For this purpose, 3 tanks were randomly arranged and assigned to each experimental diet. Fish were fed with their respective diet to apparent satiation 4 times daily. The results indicated that white blood cell, red blood cell and haemoglobin significantly responded to graded dietary Thr levels, while hematocrit didn't. Complement components (C3 and C4), total iron-binding capacity (TIBC), immunoglobulin M (IgM), superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT) increased with increasing dietary Thr levels up to 1.58-2.08% and thereafter tended to decrease. Dietary Thr regulated the gene expressions of Cu/Zn-SOD, Mn-SOD and CAT, GPx1, glutathione S-transferase mu (GST), nuclear factor erythroid 2-related factor 2 (Nrf2), heat shock protein-70 (Hsp70), tumor necrosis factor-alpha (TNF-α), apolipoprotein A-I (ApoA1), glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and fructose-bisphosphate aldolase B (ALDOB); while the gene expression of peroxiredoxin II (PrxII) was not significantly modified by graded Thr levels. These genes are involved in different functions including antioxidant, immune, and defense responses, energy metabolism and protein synthesis. Therefore, this study could provide a new molecular tool for studies in fish immunonutrition and shed light on the regulatory mechanisms that dietary Thr improved the antioxidant and immune capacities of fish. Copyright © 2015 Elsevier Ltd. All rights reserved.

  1. Total glucosides of paeony inhibit the inflammatory responses of mice with allergic contact dermatitis by restoring the balanced secretion of pro-/anti-inflammatory cytokines.

    Science.gov (United States)

    Wang, Chun; Yuan, Jun; Wu, Hua-Xun; Chang, Yan; Wang, Qing-Tong; Wu, Yu-Jing; Zhou, Peng; Yang, Xiao-Dan; Yu, Jun; Wei, Wei

    2015-02-01

    The present study aimed to investigate the regulation exerted by the total glucosides of paeony (TGP) on the production of interleukin-2 (IL-2), IL-4, IL-10 and IL-17 in the serum and lymphocytes of mice with allergic contact dermatitis (ACD). ACD in mice was induced by the repeated application of 2,4-dinitrochlorobenzene (DNCB) to their skins. The mice were orally administered TGP (35, 70, and 140mg/kg/d) and prednisone (Pre, 5mg/kg/d) from day 1 to day 7 after immunization. The inflammatory responses were evaluated by ear swelling and histological examination. Thymocyte proliferation was assayed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H tetrazolium bromide assay. The cytokine production in the serum and lymphocytes supernatant was measured by enzyme-linked immunosorbent assay. The results indicated that the topical application of DNCB to the skin provoked obvious inflammatory responses. The oral administration of TGP (70 and 140mg/kg/d) and Pre (5mg/kg/d) significantly inhibited skin inflammation, decreased the thymus and spleen indices, and inhibited thymocyte proliferation in mice treated with DNCB. Further study indicated that TGP increased IL-4 and IL-10 production but decreased the production of IL-2 and IL-17 in the serum and lymphocyte supernatant. The correlation analysis suggested significantly positive correlations between IL-2 and IL-17 production and the severity of skin inflammation, whereas negative correlations were obtained for IL-4 and IL-10 production and skin inflammation. In summary, these results suggest that the therapeutic effects of TGP on ACD may result from its regulation of the imbalanced secretion of IL-2/IL-4 and IL-10/IL-17. Copyright © 2014 Elsevier B.V. All rights reserved.

  2. CD80 and CD86 Costimulatory Molecules Differentially Regulate OT-II CD4+ T Lymphocyte Proliferation and Cytokine Response in Cocultures with Antigen-Presenting Cells Derived from Pregnant and Pseudopregnant Mice

    Directory of Open Access Journals (Sweden)

    Tomasz Maj

    2014-01-01

    Full Text Available Immune phenomena during the preimplantation period of pregnancy are poorly understood. The aim of our study was to assess the capacity for antigen presentation of splenic antigen-presenting cells (APCs derived from pregnant and pseudopregnant mice in in vitro conditions. Therefore, sorted CD11c+ dendritic cells and macrophages F4/80+ and CD11b+ presenting ovalbumin (OVA were cocultured with CD4+ T cells derived from OT-II mice’s (C57BL6/J-Tg(TcraTcrb1100Mjb/J spleen. After 132 hours of cell culture, proliferation of lymphocytes (ELISA-BrdU, activation of these cells (flow cytometry, cytokine profile (ELISA, and influence of costimulatory molecules blocking on these parameters were measured. We did not detect any differences in regulation of Th1/Th2 cytokine balance. CD86 seems to be the main costimulatory molecule involved in the proliferation response but CD80 is the main costimulatory molecule influencing cytokine secretion in pregnant mice. In conclusion, this study showed that CD80 and CD86 costimulatory molecules regulate OT-II CD4+ T lymphocyte proliferation and cytokine response in cocultures with antigen-presenting cells derived from pregnant and pseudopregnant mice. The implications of these changes still remain unclear.

  3. RACLETTE: a model for evaluating the thermal response of plasma facing components to slow high power plasma transients. Part I: Theory and description of model capabilities

    Science.gov (United States)

    Raffray, A. René; Federici, Gianfranco

    1997-04-01

    RACLETTE (Rate Analysis Code for pLasma Energy Transfer Transient Evaluation), a comprehensive but relatively simple and versatile model, was developed to help in the design analysis of plasma facing components (PFCs) under 'slow' high power transients, such as those associated with plasma vertical displacement events. The model includes all the key surface heat transfer processes such as evaporation, melting, and radiation, and their interaction with the PFC block thermal response and the coolant behaviour. This paper represents part I of two sister and complementary papers. It covers the model description, calibration and validation, and presents a number of parametric analyses shedding light on and identifying trends in the PFC armour block response to high plasma energy deposition transients. Parameters investigated include the plasma energy density and deposition time, the armour thickness and the presence of vapour shielding effects. Part II of the paper focuses on specific design analyses of ITER plasma facing components (divertor, limiter, primary first wall and baffle), including improvements in the thermal-hydraulic modeling required for better understanding the consequences of high energy deposition transients in particular for the ITER limiter case.

  4. RACLETTE: a model for evaluating the thermal response of plasma facing components to slow high power plasma transients. Pt. I. Theory and description of model capabilities

    International Nuclear Information System (INIS)

    Raffray, A.R.; Federici, G.

    1997-01-01

    For pt.II see ibid., p.101-30, 1997. RACLETTE (Rate Analysis Code for pLasma Energy Transfer Transient Evaluation), a comprehensive but relatively simple and versatile model, was developed to help in the design analysis of plasma facing components (PFCs) under 'slow' high power transients, such as those associated with plasma vertical displacement events. The model includes all the key surface heat transfer processes such as evaporation, melting, and radiation, and their interaction with the PFC block thermal response and the coolant behaviour. This paper represents part I of two sister and complementary papers. It covers the model description, calibration and validation, and presents a number of parametric analyses shedding light on and identifying trends in the PFC armour block response to high plasma energy deposition transients. Parameters investigated include the plasma energy density and deposition time, the armour thickness and the presence of vapour shielding effects. Part II of the paper focuses on specific design analyses of ITER plasma facing components (divertor, limiter, primary first wall and baffle), including improvements in the thermal-hydraulic modeling required for better understanding the consequences of high energy deposition transients in particular for the ITER limiter case. (orig.)

  5. Cytokine-producing T cell subsets in human leishmaniasis

    DEFF Research Database (Denmark)

    Kemp, Kåre

    2000-01-01

    Leishmania specific Th1/Th2 cells have been identified in humans as well as in mice. There is a correlation between the clinical outcome of the infection and the cytokine response profile. Generally, the production of Th2 cytokines leads to severe infection, whereas the production of Th1 cytokine...

  6. Immersion infection of germ-free zebrafish with Listeria monocytogenes induces transient expression of innate immune response genes

    Directory of Open Access Journals (Sweden)

    Ying eShan

    2015-04-01

    Full Text Available Zebrafish, Denio rerio, could be an alternative to other classic animal models for human infectious diseases to examine the processes of microbial infections and host-pathogen interactions in vivo because of their small body dimension but large clutch size. We established germ-free zebrafish infection models of Listeria monocytogenes through different routes of infection: oral immersion and injection via yolk sac, brain ventricle and blood island. Immersion of zebrafish larva even with 1010CFU/mL L. monocytogenes EGDe strain in egg water was unable to cause mortality, but GFP-expressing bacteria in the gut lumen could be observed in frozen sections. Several selected maker genes of the innate immune system, including cyp1a, irg1l, il1b and mmp9, were significantly induced by oral immersion not only with strain EGDe, but also with strain M7 and L. innocua, though to a lesser degree (P < 0.01. Such induction appears to be transient with peak at 48 h post-infection, but returned to basal level at 72 h post-infection. Of the three injection routes, mortality after infection by yolk sac was 80% in early stage of infection. Few eggs could survive and hatch. Injection into zebrafish embryos via brain ventricle or blood island led to progressive lethal infection. L. mocytogenes EGDe showed steady replication in the fish embryos and was far more pathogenic than strain M7, which is consistent with findings in the murine model. We conclude that zebrafish could serve as susceptible and microscopically visible infection models for L. monocytogenes via different routes and could be applied to further studies on the interactions between bacterial virulence factors and host immune responses.

  7. On the Meaning of Feedback Parameter, Transient Climate Response, and the Greenhouse Effect: Basic Considerations and the Discussion of Uncertainties

    Science.gov (United States)

    Kramm, Gerhard

    2010-07-01

    In this paper we discuss the meaning of feedback parameter, greenhouse effect and transient climate response usually related to the globally averaged energy balance model of Schneider and Mass. After scrutinizing this model and the corresponding planetary radiation balance we state that (a) the this globally averaged energy balance model is flawed by unsuitable physical considerations, (b) the planetary radiation balance for an Earth in the absence of an atmosphere is fraught by the inappropriate assumption of a uniform surface temperature, the so-called radiative equilibrium temperature of about 255 K, and (c) the effect of the radiative anthropogenic forcing, considered as a perturbation to the natural system, is much smaller than the uncertainty involved in the solution of the model of Schneider and Mass. This uncertainty is mainly related to the empirical constants suggested by various authors and used for predicting the emission of infrared radiation by the Earth's skin. Furthermore, after inserting the absorption of solar radiation by atmospheric constituents and the exchange of sensible and latent heat between the Earth and the atmosphere into the model of Schneider and Mass the surface temperatures become appreciably lesser than the radiative equilibrium temperature. Moreover, neither the model of Schneider and Mass nor the Dines-type two-layer energy balance model for the Earth-atmosphere system, both contain the planetary radiation balance for an Earth in the absence of an atmosphere as an asymptotic solution, do not provide evidence for the existence of the so-called atmospheric greenhouse effect if realistic empirical data are used.

  8. Transient Expression of CRISPR/Cas9 Machinery Targeting TcNPR3 Enhances Defense Response in Theobroma cacao.

    Science.gov (United States)

    Fister, Andrew S; Landherr, Lena; Maximova, Siela N; Guiltinan, Mark J

    2018-01-01

    Theobroma cacao , the source of cocoa, suffers significant losses to a variety of pathogens resulting in reduced incomes for millions of farmers in developing countries. Development of disease resistant cacao varieties is an essential strategy to combat this threat, but is limited by sources of genetic resistance and the slow generation time of this tropical tree crop. In this study, we present the first application of genome editing technology in cacao, using Agrobacterium-mediated transient transformation to introduce CRISPR/Cas9 components into cacao leaves and cotyledon cells. As a first proof of concept, we targeted the cacao Non-Expressor of Pathogenesis-Related 3 (TcNPR3) gene, a suppressor of the defense response. After demonstrating activity of designed single-guide RNAs (sgRNA) in vitro , we used Agrobacterium to introduce a CRISPR/Cas9 system into leaf tissue, and identified the presence of deletions in 27% of TcNPR3 copies in the treated tissues. The edited tissue exhibited an increased resistance to infection with the cacao pathogen Phytophthora tropicalis and elevated expression of downstream defense genes. Analysis of off-target mutagenesis in sequences similar to sgRNA target sites using high-throughput sequencing did not reveal mutations above background sequencing error rates. These results confirm the function of NPR3 as a repressor of the cacao immune system and demonstrate the application of CRISPR/Cas9 as a powerful functional genomics tool for cacao. Several stably transformed and genome edited somatic embryos were obtained via Agrobacterium -mediated transformation, and ongoing work will test the effectiveness of this approach at a whole plant level.

  9. Altered Memory T-Cell Responses to Bacillus Calmette-Guerin and Tetanus Toxoid Vaccination and Altered Cytokine Responses to Polyclonal Stimulation in HIV-Exposed Uninfected Kenyan Infants.

    Science.gov (United States)

    Garcia-Knight, Miguel A; Nduati, Eunice; Hassan, Amin S; Gambo, Faith; Odera, Dennis; Etyang, Timothy J; Hajj, Nassim J; Berkley, James Alexander; Urban, Britta C; Rowland-Jones, Sarah L

    2015-01-01

    Implementation of successful prevention of mother-to-child transmission of HIV strategies has resulted in an increased population of HIV-exposed uninfected (HEU) infants. HEU infants have higher rates of morbidity and mortality than HIV-unexposed (HU) infants. Numerous factors may contribute to poor health in HEU infants including immunological alterations. The present study assessed T-cell phenotype and function in HEU infants with a focus on memory Th1 responses to vaccination. We compared cross-sectionally selected parameters at 3 and 12 months of age in HIV-exposed (n = 42) and HU (n = 28) Kenyan infants. We measured ex vivo activated and bulk memory CD4 and CD8 T-cells and regulatory T-cells by flow cytometry. In addition, we measured the magnitude, quality and memory phenotype of antigen-specific T-cell responses to Bacillus Calmette-Guerin and Tetanus Toxoid vaccine antigens, and the magnitude and quality of the T cell response following polyclonal stimulation with staphylococcal enterotoxin B. Finally, the influence of maternal disease markers on the immunological parameters measured was assessed in HEU infants. Few perturbations were detected in ex vivo T-cell subsets, though amongst HEU infants maternal HIV viral load positively correlated with CD8 T cell immune activation at 12 months. Conversely, we observed age-dependent differences in the magnitude and polyfunctionality of IL-2 and TNF-α responses to vaccine antigens particularly in Th1 cells. These changes mirrored those seen following polyclonal stimulation, where at 3 months, cytokine responses were higher in HEU infants compared to HU infants, and at 12 months, HEU infant cytoki