Cytokine and immunoglobulin production by PWM-stimulated peripheral and tumor-infiltrating lymphocytes of undifferentiated nasopharyngeal carcinoma (NPC patients

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Bouzouita Kamel

2004-09-01

Full Text Available Abstract Background Undifferentiated Nasopharyngeal Carcinoma (NPC patients show a characteristic pattern of antibody responses to the Epstein-Barr virus (EBV which is regularly associated with this tumor. However, no EBV-specific cytotoxic activity is detectable by the standard chromium-release assay at both peripheral and intratumoral levels. The mechanisms underlying this discrepancy between the humoral and cellular immune responses in NPC are still unknown, but might be related to an imbalance in immunoregulatory interleukin production. In this report, we investigated the ability of peripheral (PBL and tumor- infiltrating (TIL lymphocytes of undifferentiated NPC patients to produce in vitro three interleukins (IL-2, IL-6, IL-10 and three immunoglobulin isotypes (IgM, IgG, IgA. Methods Lymphocytes from 17 patients and 17 controls were cultured in the presence of Pokeweed mitogen (PWM for 12 days and their culture supernatants were tested for interleukins and immunoglobulins by specific enzyme-linked immunosorbent assays (ELISA. Data were analysed using Student's t-test and probability values below 5% were considered significant. Results The data obtained indicated that TIL of NPC patients produced significantly more IL-2 (p = 0,0002, IL-10 (p = 0,020, IgM (p= 0,0003 and IgG (p Conclusion Taken together, our data reinforce the possibility of an imbalance in immunoregulatory interleukin production in NPC patients. An increased ability to produce cytokines such as IL-10 may underlie the discrepancy between humoral and cellular immune responses characteristic of NPC.

Cytogenic follow-up studies in six radiation accident victims 16 and 17 years post-exposure

International Nuclear Information System (INIS)

Littlefield, L.G.; Joiner, E.E.

1978-01-01

Detailed cytogenetic evaluations were recently conducted in cultured lymphocytes from six men accidentally exposed to fission neutron and gamma radiation in 1958 (dose range 22.8-365 rads). Two-day lymphocyte cultures stimulated with phytohaemagglutinin (PHA) and seven-day cultures stimulated with pokeweed mitogen (PWM) were initiated on all six men for routine microscopic and karyotypic analysis. PHA-stimulated cultures from the two men with the highest exposures were also evaluated using Giemsa-banding procedures. Approximately 9% of the metaphases in the PHA cultures and 11% of the metaphases in the PWM cultures were found to have residual radiation-induced aberrations (symmetrical and asymmetrical exchanges and deletions). In both the PHA and PWM cultures the highest frequencies of lesions were observed in preparations from three men with the highest radiation exposures. Among the abnormal metaphases from the various PHA cultures five possible clones were identified (two or more cells having apparently identical lesions) whereas no stemlines were detected in the PWM cultures. The frequency of stable lesions in 92 banded metaphases from the two men with the highest exposures did not differ significantly from the frequency of lesions detected in 300 metaphases evaluated with routine staining and karyotypic procedures. These data suggest that radiation-damaged lymphocytes responsive to mitogenic stimulation by PHA and PWM may survive for many years following exposure, that the frequency of lymphocytes with persistent aberrations can be roughly correlated with dose, and that in some instances cells bearing 'stable' radiation-induced lesions may propagate in vivo. The findings also show that banding procedures, compared with routine microscopic and karyotypic methods, do not significantly improve the rate of detection of symmetrical lesions in lymphocytes from irradiated persons

Postoperative radiation therapy and adjuvant chemoimmunotherapy in breast cancer. Aspects of timing and immune competence

Energy Technology Data Exchange (ETDEWEB)

Klefstroem, P.; Nuortio, L.; Taskinen, E.

The effects of radiation therapy and adjuvant chemoimmunotherapy on the immune competence of patients with breast cancer were investigated. The tests performed included intradermal tuberculin tests, T- and B-lymphocyte counts, and lymphocyte blast transformation tests; phytohemagglutinin (PHA), concanavalin A (ConA) and pokeweed mitogen (PMW) were used as mitogens. Enhancement in lymphocyte proliferative response to mitogenic stimulation by PHA and PMW was seen in patients after 3 courses of chemotherapy + levamisole, whereas irradiation given after chemotherapy caused long-lasting depression in response to PHA and PWM (not significant). T-lymphocyte counts were also lower after irradiation than after chemoimmunotherapy. Clinically, the 16 patients treated with radiation therapy after chemotherapy exhibited a higher recurrence rate than the 24 patients treated first by irradiation. Enhanced reactivity to tuberculin tests occurred generally in patients receiving a planned treatment including irradiation, chemotherapy (5-fluorouracil, doxorubicin, cyclophosphamide) and levamisole. Enhancement of reactivity was seen more often in patients who had not relapsed.

Effects of polycationic compounds on mitogen stimulation

DEFF Research Database (Denmark)

Heron, I; Larsen, B; Hokland, M

1981-01-01

The effects of polycations added to phytomitogen stimulated human lymphocyte cultures have been studied. Within certain dose ranges all polycations tested gave rise to augmented thymidine uptake in mitogen stimulated cultures. The optimum enhancing concentrations of polycations was depending on t...

Cytokine and immunoglobulin production by PWM-stimulated peripheral and tumor-infiltrating lymphocytes of undifferentiated nasopharyngeal carcinoma (NPC) patients

International Nuclear Information System (INIS)

Fliss-Jaber, Lilia; Houissa-Kastally, Radhia; Bouzouita, Kamel; Khediri, Naceur; Khelifa, Ridha

2004-01-01

Undifferentiated Nasopharyngeal Carcinoma (NPC) patients show a characteristic pattern of antibody responses to the Epstein-Barr virus (EBV) which is regularly associated with this tumor. However, no EBV-specific cytotoxic activity is detectable by the standard chromium-release assay at both peripheral and intratumoral levels. The mechanisms underlying this discrepancy between the humoral and cellular immune responses in NPC are still unknown, but might be related to an imbalance in immunoregulatory interleukin production. In this report, we investigated the ability of peripheral (PBL) and tumor- infiltrating (TIL) lymphocytes of undifferentiated NPC patients to produce in vitro three interleukins (IL-2, IL-6, IL-10) and three immunoglobulin isotypes (IgM, IgG, IgA). Lymphocytes from 17 patients and 17 controls were cultured in the presence of Pokeweed mitogen (PWM) for 12 days and their culture supernatants were tested for interleukins and immunoglobulins by specific enzyme-linked immunosorbent assays (ELISA). Data were analysed using Student's t-test and probability values below 5% were considered significant. The data obtained indicated that TIL of NPC patients produced significantly more IL-2 (p = 0,0002), IL-10 (p = 0,020), IgM (p= 0,0003) and IgG (p < 0,0001) than their PBL. On the other hand, patients PBL produced significantly higher levels of IL-2 (p = 0,022), IL-10 (p = 0,016) and IgM (p = 0,004) than those of controls. No significant differences for IL-6 and IgA were observed. Taken together, our data reinforce the possibility of an imbalance in immunoregulatory interleukin production in NPC patients. An increased ability to produce cytokines such as IL-10 may underlie the discrepancy between humoral and cellular immune responses characteristic of NPC

Autoreactive lymphocytes in thyroid disorders. 2. Comparison of anti-thyroglobulin antibody production by plaque-forming cell, radio-immunological and enzyme-linked immunosorbent assays

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Petersen, J; Feldt-Rasmussen, U; Siersbaek-Nielsen, K; Hoeier-Madsen, M; Larsen, F; Husby, S

1986-01-01

Blood mononuclear cells (MNC) from 9 randomly selected patients with autoimmune thyroiditis were stimulated in vitro with pokeweed mitogen (PWM), a polyclonal B lymphocyte activator. The secretion of immunoglobulins (Ig) and anti-thyroglobulin antibodies (TgAb) was assayed by means of haemolytic plaque-forming cell (PFC) assays, radioimmune assay (RIA) and enzyme-linked immunosorbent assays (ELISA). Total Ig and TgAb production was maximal using MNC cultured at 1.0 x 10/sup 6//ml as estimated by PFC, RIA and ELISA. The Ig and TgAb production as measured by RIA and ELISA was 1.5 - 3 times higher after 12 days' culture compared to 6 days' culture. Ig and TgAb production measured by PFC-assays at day 6 correlated positively to the results obtained by RIA and ELISA at day 12. PWM-induced TgAb secretion correlated positively to TgAb titres in serum. As judged by PFC, TgAb production was found in 8/9 patients; about 5% (range 0 - 7.9%) of the total PWM-stimulated IgG-secreting cells were involved in TgAb secretion. TgAb production as measured by ELISA and RIA was found in 6/9 patients. By reference to an affinity-purified human TgAb preparation, the TgAb secretion was about 0.7% (range 0 - 21.3%) of the total PWM-induced IgG secretion.

Autoreactive lymphocytes in thyroid disorders. 2

International Nuclear Information System (INIS)

Petersen, J.; Feldt-Rasmussen, U.; Siersbaek-Nielsen, K.; Hoeier-Madsen, M.; Larsen, F.; Husby, S.

1986-01-01

Blood mononuclear cells (MNC) from 9 randomly selected patients with autoimmune thyroiditis were stimulated in vitro with pokeweed mitogen (PWM), a polyclonal B lymphocyte activator. The secretion of immunoglobulins (Ig) and anti-thyroglobulin antibodies (TgAb) was assayed by means of haemolytic plaque-forming cell (PFC) assays, radioimmune assay (RIA) and enzyme-linked immunosorbent assays (ELISA). Total Ig and TgAb production was maximal using MNC cultured at 1.0 x 10 6 /ml as estimated by PFC, RIA and ELISA. The Ig and TgAb production as measured by RIA and ELISA was 1.5 - 3 times higher after 12 days' culture compared to 6 days' culture. Ig and TgAb production measured by PFC-assays at day 6 correlated positively to the results obtained by RIA and ELISA at day 12. PWM-induced TgAb secretion correlated positively to TgAb titres in serum. As judged by PFC, TgAb production was found in 8/9 patients; about 5% (range 0 - 7.9%) of the total PWM-stimulated IgG-secreting cells were involved in TgAb secretion. TgAb production as measured by ELISA and RIA was found in 6/9 patients. By reference to an affinity-purified human TgAb preparation, the TgAb secretion was about 0.7% (range 0 - 21.3%) of the total PWM-induced IgG secretion. (author)

Subpopulation of human helper and suppressor T lymphocytes

International Nuclear Information System (INIS)

Venkataraman, M.; Levin, R.D.; Westerman, M.P.

1983-01-01

Mitogen driven differentiation of normal human mononuclear cells is a well-established model for the study of antibody synthesis in man. In certain rare individuals who are clinically normal, unfractionated mononuclear cells or a mixture of purified B plus T lymphocytes differentiate into immunoglobulin producing cells in response to purified protein derivative of tuberculin (PPD) but not in response to pokeweed mitogen (PWM). To evaluate this observation we have irradiated T cells from such individuals to eliminate naturally occurring suppressor T cell activity and then added the irradiated T cells back to autologous B cells before culture. The B cells then responded to PWM. The original PPD responses of cells from these individuals were now significantly reduced. Although, there was no difference between PWM nonresponders and responders in the number of OKT-8 positive cells, elimination of OKT-8 positive cells in the PWM nonresponders with OKT-8 monoclonal antibody and complement resulted in a significantly increased response to PWM. This study indicates that there are suppressor T cells which specifically inhibit B cell response to PWM without affecting the PPD response. These results also show that the helper T cells involved in the PWM response are radioresistant and those involved in the PPD response are radiosensitive

Failure of attenuated canine distemper virus (Rockborn strain) to suppress lymphocyte blastogenesis in dogs.

Science.gov (United States)

Schultz, R D

1976-01-01

The attenuated Rockborn strain of canine distemper virus is commonly used in commercial vaccines. Since immunosuppression is a common feature of virulent (Snyder Hill) distemper virus infection of the dog, an evaluation of the cellular immune functions of dogs given inoculums of the less virulent Rockborn strain was done using lymphocyte blastogenesis responses to various mitogens. Unlike the viruslent Snyder Hill strain, the attenuated distemper virus did not alter lymphocyte blastogenesis responses to phytohemaglutinin (PHA) and pokeweed mitogen (PWM) which are considered in vitro correlates of T and B cell immunity.

Differential effect on TCR:CD3 stimulation of a 90-kD glycoprotein (gp90/Mac-2BP), a member of the scavenger receptor cysteine-rich domain protein family

DEFF Research Database (Denmark)

Silvestri, B; Calderazzo, F; Coppola, V

1998-01-01

We studied the effects of a 90-kD glycoprotein (gp90/Mac-2BP) belonging to the scavenger receptor family, present in normal serum and at increased levels in inflammatory disease and cancer patients, on some T cell function parameters. Whereas the lymphocyte proliferative response to non-specific ......We studied the effects of a 90-kD glycoprotein (gp90/Mac-2BP) belonging to the scavenger receptor family, present in normal serum and at increased levels in inflammatory disease and cancer patients, on some T cell function parameters. Whereas the lymphocyte proliferative response to non......-specific mitogens such as phytohaemagglutinin (PHA) and concanavalin A (Con A), but not pokeweed mitogen (PWM), was strongly reduced, probably due to the lectin-binding properties of gp90/Mac-2BP, the response to T cell receptor (TCR) agonists such as superantigens and allogeneic cells was potentiated. When...... lymphocytes were stimulated with different anti-TCR:CD3 MoAbs, both in soluble and solid-phase form, gp90/Mac-2BP was able to down-regulate the proliferative response to anti-CD3 MoAb, whereas the response to anti-TCR alphabeta MoAb was enhanced. A similar differential effect was observed when a MoAb against...

Ontogeny of surface markers on functionally distinct T cell subsets in the chicken.

Science.gov (United States)

Traill, K N; Böck, G; Boyd, R L; Ratheiser, K; Wick, G

1984-01-01

Three subsets of chicken peripheral T cells (T1, T2 and T3) have been identified in peripheral blood of adult chickens on the basis of fluorescence intensity after staining with certain xenogeneic anti-thymus cell sera (from turkeys and rabbits). They differentiate between 3-10 weeks of age in parallel with development of responsiveness to the mitogens concanavalin A (Con A), phytohemagglutinin (PHA) and pokeweed mitogen (PWM). Functional tests on the T subsets, sorted with a fluorescence-activated cell sorter, have shown that T2, 3 cells respond to Con A, PHA and PWM and are capable of eliciting a graft-vs.-host reaction (GvHR). In contrast, although T1 cells respond to Con A, they respond poorly to PHA and not at all to PWM or in GvHR. There was some indication of cooperation between T1 and T2,3 cells for the PHA response. Parallels between these chicken subsets and helper and suppressor/cytotoxic subsets in mammalian systems are discussed.

Prognostic value of immunologic abnormalities and HIV antigenemia in asymptomatic HIV-infected individuals: proposal of immunologic staging

DEFF Research Database (Denmark)

Hofmann, B; Bygbjerg, Ib Christian; Dickmeiss, E

1989-01-01

The prognostic value of various immunologic tests was investigated in 150 HIV-seropositive homosexual men, who were initially without HIV-related symptoms or AIDS and who were followed for a median of 12 months (range 3-28 months). The laboratory investigations included HIV antigen in serum, total...... lymphocyte count, T-helper (CD4) and T-cytotoxic/suppressor (CD8) counts, and lymphocyte transformation responses to the mitogens phytohemagglutinin (PHA) and pokeweed mitogen (PWM), and to antigenic extracts from Candida albicans and cytomegalovirus. 24 individuals developed HIV-related symptoms or AIDS (11...... cases). All parameters except the CD8 count were of prognostic value, but a multivariate analysis of symptom-free survival showed that HIV antigenemia, a CD4 count less than 0.5 x 10(9)/l, and relative response to PWM below 25% of controls contained all the prognostic information. Individuals abnormal...

Differentiation of human B lymphocyte subpopulations induced by an alloreactive helper T-cell clone

International Nuclear Information System (INIS)

Anderson, S.J.; Hummell, D.S.; Lawton, A.R.

1988-01-01

We have used cloned alloreactive helper T cells to determine if direct T cell-B cell interaction can induce differentiation of human peripheral blood B cells which do not respond to pokeweed mitogen (PWM). T-cell clone 2F8 was derived from a one-way mixed lymphocyte reaction. 2F8 cells are T3+T4+T8-IL-2R+ and proliferate in response to irradiated stimulator cells, but not autologous cells, in the absence of exogenous interleukin-2. 2F8 cells provide allospecific help for polyclonal proliferation and differentiation of B cells in the absence of any other stimulus. The magnitude of this response is comparable to that of the response of the same B cells to PWM and fresh autologous T cells. 2F8 cells could also provide nonspecific help for unrelated donor B cells in the presence of PWM, with no requirement for costimulation by irradiated stimulator cells. Allospecific stimulation of B cells was completely inhibited by antibodies to class II major histocompatibility complex (MHC) framework determinants and was abrogated by 1000-rad irradiation. Cloned 2F8 T cells stimulated differentiation of both small, high-density B cells and larger B cells, generating up to 30% plasma cells with either fraction. B cells forming rosettes with mouse erythrocytes were also induced to differentiate by the helper T cell clone. As found previously, neither small, high-density B cells nor mouse rosette+ B cells responded well to PWM. Direct interaction with allospecific T cells induces differentiation of a broader spectrum of B cells than soluble growth and differentiation factors in conjunction with polyclonal activators such as PWM and protein A containing staphylococci

Effect of irradiation on T-cell suppression of ELISA-determined Ig production by human blood B-cells in vitro

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Wasserman, J; Stedingk, L.V. von; Biberfeld, G; Petrini, B; Blomgren, H; Baral, E [Central Microbiologcal Lab. of Stockholm County Council (Sweden)

1979-11-01

Human blood B-lymphocytes were co-cultured with in vitro irradiated allogeneic or autologous T-lymphocytes in the presence of pokeweed mitogen (PWM). The production of IgG, IgM and IgA, as assessed by the enzyme-linked immunosorbent assay (ELISA) was increased 2-7 times, as compared to values obtained with non-irradiated T-lymphocytes. It was suggested that the increase of Ig production was due to the selective radiosensitivity of T-lymphocytes with suppressor function. (author).

Potassium humate inhibits complement activation and the production of inflammatory cytokines in vitro

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van Rensburg, C.E.J.; Naude, P.J. [University of Pretoria, Pretoria (South Africa)

2009-08-15

The effects of brown coal derived potassium humate on lymphocyte proliferation, cytokine production and complement activation were investigated in vitro. Potassium humate increased lymphocyte proliferation of phytohaemaglutinin A (PHA) and pokeweed mitogen (PWM) stimulated mononuclear lymphocytes (MNL) in vitro from concentrations of 20 to 80 {mu} g/ml, in a dose dependant manner. On the other hand potassium humate, at 40 {mu} g/ml, significantly inhibited the release of TNF-alpha, IL-1 beta, IL-6 and IL-10 by PHA stimulated MNL. Regarding complement activation it was found that potassium humate inhibits the activation of both the alternative and classical pathways without affecting the stability of the red blood cell membranes. These results indicate that the anti-inflammatory potential of potassium humate could be partially due to the inhibition of pro-inflammatory cytokines responsible for the initiation of these reactions as well as inhibition of complement activation. The increased lymphocyte proliferation observed, might be due to increased IL-2 production as previously been documented.

Effect of irradiation on human T-cell proliferation: low dose irradiation stimulates mitogen-induced proliferation and function of the suppressor/cytotoxic T-cell subset

International Nuclear Information System (INIS)

Gualde, N.; Goodwin, J.S.

1984-01-01

Unfractionated human T cells exposed to 10-50 rad of X irradiation incorporated less [ 3 H]thymidine than nonirradiated T cells when subsequently cultured with PHA or Con A. The cytotoxic/suppressor T-cell subset, isolated as either OKT8(+) or OKT4(-) cells, demonstrated significantly enhanced [ 3 H]thymidine incorporation in PHA- or Con A-stimulated cultures after exposure to 10-50 rad, compared to unirradiated cells, while the proliferation of the OKT4(+) helper/inducer subset was inhibited by low dose irradiation. It has been previously reported that approximately 30% of the cytotoxic/suppressor subset also stains with OKM1. When the cytotoxic/suppressor subset was further subdivided into OKT4(-), OKM1(+), and OKT4(-), OKM1(-) cells, proliferation of the OKT4(-), OKM1(+) population was inhibited by exposure to 25 rad while proliferation of the OKT4(-), OKM1(-) population was stimulated. The increase in proliferation of the cytotoxic/suppressor T-cell subset after low dose irradiation is paralleled by an increase in suppressor activity of these cells. T cells exposed to 25 rad and then cultured with Con A for 48 hr caused greater inhibition of IgG production when added to fresh autologous lymphocytes stimulated by pokeweed mitogen than did unirradiated cells. Thus, low dose irradiation enhances both the proliferation and function of the human suppressor T-cell subset

Control of polyclonal immunoglobulin production from human lymphocytes by leukotrienes; leukotriene B4 induces an OKT8(+), radiosensitive suppressor cell from resting, human OKT8(-) T cells

International Nuclear Information System (INIS)

Atluru, D.; Goodwin, J.S.

1984-01-01

We report that leukotriene B4 (LTB4), a 5-lipoxygenase metabolite of arachidonic acid, is a potent suppressor of polyclonal Ig production in pokeweed mitogen (PWM)-stimulated cultures of human peripheral blood lymphocytes, while LTC4 and LTD4 have little activity in this system. Preincubation of T cells with LTB4 in nanomolar to picomolar concentrations rendered these cells suppressive of Ig production in subsequent PWM-stimulated cultures of fresh, autologous B + T cells. This LTB4-induced suppressor cell was radiosensitive, and its generation could be blocked by cyclohexamide but not by mitomycin C. The LTB4-induced suppressor cell was OKT8(+), while the precursor for the cell could be OKT8(-). The incubation of OKT8(-) T cells with LTB4 for 18 h resulted in the appearance of the OKT8(+) on 10-20% of the cells, and this could be blocked by cyclohexamide but not by mitomycin C. Thus, LTB4 in very low concentrations induces a radiosensitive OKT8(+) suppressor cell from OKT8(-) cells. In this regard, LTB4 is three to six orders of magnitude more potent than any endogenous hormonal inducer of suppressor cells previously described. Glucocorticosteroids, which block suppressor cell induction in many systems, may act by inhibiting endogenous production of LTB4

Manifestation of radiaton injury of human lymphocytes using PHA mitogenic stimulation in different culture systems

International Nuclear Information System (INIS)

Horky, J.

1986-01-01

The proliferative response of human lymphocytes to phytohemagglutinin in vitro is affected by X-irradiation. Dose-related changes in mitogenic stimulation of irradiated lymphocytes were compared for two culture systems - the cultivation of separated lymphocytes and the cultivation of whole blood. In the whole blood cultures, the proliferative activity of stimulated lyphocytes was markedly and reproducibly depressed by irradiation. An exponential curve could be fitted to the values of mitogenic response within a dose range from 0 to 2.5 Gy with high correlation. In a modified test where the mitogenic stimulus was given after a 24 h delay, depression in the response was even more pronounced. Radiosensitivity of human lymphocytes as determined by means of mitogenic stimulation in the whole blood cultures appears to be a characteristic individual feature. The mean D 37 value of the radiation-induced depression in mitogenic response in a group of 20 healthy donors was 2.5 Gy in the standard test and 2.0 Gy in the test with a delayed mitogenic stimulus. In contrast, the data obtained from separated lymphocyte cultures were characterized by a high degree of test-to-test variability and by much lower radiosensitivity. The possible mechanisms of these distinctive manifestations of the same primary radiation injury are discussed. (author) 3 tabs., 2 figs., 12 refs

Stimulated mitogen-activated protein kinase is necessary but not sufficient for the mitogenic response to angiotensin II. A role for phospholipase D.

Science.gov (United States)

Wilkie, N; Morton, C; Ng, L L; Boarder, M R

1996-12-13

Activation of the mitogen-activated protein kinase (MAPK) cascade has been widely associated with cell proliferation; previous studies have shown that angiotensin II (AII), acting on 7-transmembrane G protein-coupled receptors, stimulates the MAPK pathway. In this report we investigate whether the MAPK pathway is required for the mitogenic response to AII stimulation of vascular smooth muscle cells derived from the hypertensive rat (SHR-VSM). AII stimulates the phosphorylation of MAPK, as determined by Western blot specific for the tyrosine 204 phosphorylated form of the protein. This MAPK phosphorylation was inhibited by the presence of the inhibitor of MAPK kinase activation, PD 098059. Using a peptide kinase assay shown to measure the p42 and p44 isoforms of MAPK, the stimulated response to AII was inhibited by PD 098059 with an IC50 of 15.6 +/- 1.6 microM. The AII stimulation of [3H]thymidine incorporation was inhibited by PD 098059 with an IC50 of 17.8 +/- 3.1 microM. PD 098059 had no effect on AII-stimulated phospholipase C or phospholipase D (PLD) activity. When the SHR-VSM cells were stimulated with phorbol ester, there was an activation of MAPK similar in size and duration to the response to AII, but there was no significant enhancement of [3H]thymidine incorporation. There was also no activation of PLD by phorbol ester, while AII produced a robust PLD response. Diversion of the product of the PLD reaction by 1-butanol caused a partial loss of the [3H]thymidine response; this did not occur with tertiary butanol, which did not interfere with the PLD reaction. These results show that in these cells the MAPK cascade is required but not sufficient for the mitogenic response to AII, and suggest that the full mitogenic response requires both MAPK in conjunction with other signaling components, one of which is PLD.

Increased rate of repair of ultraviolet-induced DNA strand breaks in mitogen stimulated lymphocytes

Energy Technology Data Exchange (ETDEWEB)

Hamlet, S.M.; Lavin, M.F.; Jennings, P.A. (Queensland Univ., St. Lucia (Australia). Dept. of Biochemistry; Queensland Univ., St. Lucia (Australia). Dept. of Veterinary Pathology; Queensland Univ. St. Lucia (Australia). Dept. of Public Health)

1982-05-01

Previous results have shown that phytohaemagglutinin-stimulated bovine lymphocytes exhibit a peak of ultraviolet-induced DNA repair synthesis 3 to 4 days after addition of mitogen. The level of repair synthesis was approximately tenfold higher than that in unstimulated lymphocytes. These studies have been extended to examine the rate of repair of strand breaks in U.V.-irradiated bovine lymphocytes. The extent of breakage of DNA was shown to be the same in mitogen-stimulated and unstimulated lymphocytes from two breeds of cattle, when determined by sedimentation of nucleoids on sucrose gradients. However, in mitogen-stimulated cells the time taken to repair DNA strand breaks was 6 hours compared with 12 hours in stationary phase lymphocytes after a U.V. dose of 5 J/m/sup 2/. These results suggest that the increased rate of repair of strand breaks is due to the induction of enzymes involved at the post-incision stage of DNA repair. Thus the increased level of repair synthesis observed in earlier work correlates with an increased rate of repair of DNA strand breaks in phytohaemagglutinin-stimulated bovine lymphocytes.

Increased rate of repair of ultraviolet-induced DNA strand breaks in mitogen stimulated lymphocytes

International Nuclear Information System (INIS)

Hamlet, S.M.; Lavin, M.F.; Jennings, P.A.; Queensland Univ., St. Lucia; Queensland Univ. St. Lucia

1982-01-01

Previous results have shown that phytohaemagglutinin-stimulated bovine lymphocytes exhibit a peak of ultraviolet-induced DNA repair synthesis 3 to 4 days after addition of mitogen. The level of repair synthesis was approximately tenfold higher than that in unstimulated lymphocytes. These studies have been extended to examine the rate of repair of strand breaks in U.V.-irradiated bovine lymphocytes. The extent of breakage of DNA was shown to be the same in mitogen-stimulated and unstimulated lymphocytes from two breeds of cattle, when determined by sedimentation of nucleoids on sucrose gradients. However, in mitogen-stimulated cells the time taken to repair DNA strand breaks was 6 hours compared with 12 hours in stationary phase lymphocytes after a U.V. dose of 5 J/m 2 . These results suggest that the increased rate of repair of strand breaks is due to the induction of enzymes involved at the post-incision stage of DNA repair. Thus the increased level of repair synthesis observed in earlier work correlates with an increased rate of repair of DNA strand breaks in phytohaemagglutinin-stimulated bovine lymphocytes. (author)

Application of a new ultra-microculture system. II. Stimulation of human B lymphocytes.

Science.gov (United States)

Ulmer, A J; Gruber, M; Flad, H D

1988-07-22

An ultra-microtechnique for culturing human B-lymphocytes in glass capillary tubes using a volume of 2 microliter is described. The advantage of this ultra-microculture system is that only a small number of lymphocytes and minute amounts of culture medium (or test factors) are required. Optimal culture conditions for the formation of Ig-secreting plaque-forming cells (PFC) after stimulation of mononuclear cells with pokeweed mitogen are given. Furthermore it is shown that immunoglobulin secreted into culture supernatants by purified B cells in the presence of T cell subsets can be measured in a microELISA.

Late A-bomb effects on proliferation and mitotic inhibition of T- and B-lymphocytes

Energy Technology Data Exchange (ETDEWEB)

Suzuki, Kazuo; Yoshimoto, Yasuhiko; Sasagawa, Sumiko; Sakatani, Tatsuichiro; Macchi, M; Fujikura, Toshio; Pirofsky, B; Hamada, Tadao

1984-11-01

In order to investigate late effects of ionization radiation and aging on T- and B-lymphocytes, mitotic ability of T- and B-lymphocytes in the peripheral blood of 266 A-bomb survivors was examined by determining the incorporation of (/sup 3/H)-thymidine. Phytohemagglutinin (PHA) and pokeweed mitogen (PWM) were used as inducers. Furthermore, mitotic inhibition of lymphocytes induced by a lymphatic inhibitor which was in part prepared from ulex seed extracts (USE) was examined. A decreased reaction of peripheral lymphocytes to PHA was seen in men exposed to 100-199 rad; a decreased reaction to PWM was seen in women exposed to more than 200 rad. According to the age group at examination, these decreased reactions were remarkable in men aged 60 years or younger and women aged 60 years or older. Among men less than 60-year-old exposed to 100-199 rad, PWM-induced mitosis of lymphocytes tended to be inhibited remarkably by USE. These results suggest the involvement of late A-bomb effects in mitotic regulation of T- and B-lymphocytes of aged A-bomb survivors.

Optimized choice of method for determining proliferation response of peripheral lymphocytes to mitogens in low dose irradiation with cyclotron fast neutrons

International Nuclear Information System (INIS)

Refka, Z.; Svec, M.; Aganov, P.; Svoboda, V.; Podzimek, F.

1989-01-01

Heparinized venous blood sampled from seven donors was irradiated with doses of 0.1; 0.25; 0.5; 1.0; 2.0 and 3.0 Gy of fast neutrons of a mean energy of 7.6 MeV using the U 120 M isochronous cyclotron. A non-irradiated control sample was also prepared. A lymphoblastic transformation test was conducted with both the intact and irradiated samples. The samples were cultivated in the RPMI-1640 medium with and without a mitogen addition, this in five time variants, viz., for 48, 72, 90, 96 and 120 hours. The proliferation was monitored of lymphocytes stimulated with mitogens PHA, CON-A and PWM in dependence on the time of cultivation and on the radiation dose. The dose dependent relative response was also studied of the irradiated lymphocytes. (E.J.). 8 figs., 1 tab., 18 refs

Human prostatic cancer cells, PC3, elaborate mitogenic activity which selectively stimulates human bone cells

International Nuclear Information System (INIS)

Perkel, V.S.; Mohan, S.; Herring, S.J.; Baylink, D.J.; Linkhart, T.A.

1990-01-01

Prostatic cancer typically produces osteoblastic metastases which are not attended by marrow fibrosis. In the present study we sought to test the hypothesis that prostatic cancer cells produce factor(s) which act selectively on human osteoblasts. Such a paracrine mechanism would explain the observed increase in osteoblasts, unaccompanied by an increase in marrow fibroblasts. To test this hypothesis we investigated the mitogenic activity released by the human prostatic tumor cell line, PC3. PC3 cells have been reported previously to produce mitogenic activity for cells that was relatively specific for rat osteoblasts compared to rat fibroblasts. However, the effects of this activity on human cells has not been examined previously. PC3-conditioned medium (CM) (5-50 micrograms CM protein/ml) stimulated human osteoblast proliferation by 200-950% yet did not stimulate human fibroblast proliferation ([3H]thymidine incorporation). PC3 CM also increased cell numbers in human osteoblast but not fibroblast cell cultures. To determine whether the osteoblast-specific mitogenic activity could be attributed to known bone growth factors, specific assays for these growth factors were performed. PC3 CM contained 10 pg insulin-like growth factor (IGF) I, less than 2 pg IGF II, 54 pg basic fibroblast growth factor, and 16 pg transforming growth factor beta/microgram CM protein. None of these growth factors alone or in combination could account for the observed osteoblast-specific PC3 cell-derived mitogenic activity. Furthermore, when 5 micrograms/ml PC3 CM was tested in combination with maximally effective concentrations of either basic fibroblast growth factor, IGF I, IGF II, or transforming growth factor beta, it produced an additive effect suggesting that PC3 CM stimulates osteoblast proliferation by a mechanism independent of these bone mitogens

Effects of atomic bomb radiation on differentiation of B lymphocytes and on the function of concanavalin A-induced suppressor T lymphocytes

International Nuclear Information System (INIS)

Yamada, Y.; Neriishi, S.; Ishimaru, T.; Shimba, N.; Hamilton, H.B.; Ohgushi, Y.; Koyanagi, M.; Ichimaru, M.

1985-01-01

The differentiation of peripheral blood B lymphocytes into immunoglobulin-producing cells (Ig-PC) by pokeweed mitogen (PWM) and the function of concanavalin A (Con A)-induced suppressor T lymphocytes were examined to elucidate the late effects of atomic bomb radiation. A total of 140 individuals, 70 with an exposure dose of 100 rad or more and an equal number with an exposure dose of 0 rad matched by sex and age, were selected from the Nagasaki Adult Health Study (AHS) sample. Both the differentiation of peripheral blood B lymphocytes into Ig-PC by PWM and the function of Con A-induced suppressor T lymphocytes tended to be more depressed in the exposed group than in the control group, but a statistically significant difference could not be observed between the two groups. The function of Con A-induced suppressor T lymphocytes tended to decrease with age, but a statistical significance was detected only for percentage suppression against IgM-PC

Effect of interleukin-2 and methylprednisolone on in vitro transformation of uremic lymphocytes

DEFF Research Database (Denmark)

Langhoff, E; Ladefoged, J; Ødum, Niels

1986-01-01

The functional relationship in vitro between mitogen-induced lymphocyte transformation, lymphocyte response to interleukin-2 (IL-2) and steroid, and production of IL-2 was examined in patients with chronic renal failure on hemodialysis (HD) or on continuous ambulatory peritoneal dialysis (CAPD......). The lymphocyte responses to optimal stimulation with phytohemagglutinin, concanavalin A, and pokeweed mitogen were depressed in lymphocyte cultures from HD patients, while CAPD lymphocyte cultures responded normally. However, at suboptimal phytohemagglutinin stimulation both CAPD lymphocyte and HD lymphocyte...... responses were subnormal. Uremic lymphocyte cultures were more sensitive to the immunosuppressive effect of methylprednisolone. Addition of IL-2 normalized the phytohemagglutinin responses of suboptimally stimulated CAPD lymphocyte cultures and clearly improved the mitogen responses of the HD lymphocyte...

Pokeweed Antiviral Protein: Its Cytotoxicity Mechanism and Applications in Plant Disease Resistance

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Rong Di

2015-03-01

Full Text Available Pokeweed antiviral protein (PAP is a 29 kDa type I ribosome inactivating protein (RIP found in pokeweed plants. Pokeweed produces different forms of PAP. This review focuses on the spring form of PAP isolated from Phytolacca americana leaves. PAP exerts its cytotoxicity by removing a specific adenine from the α-sarcin/ricin loop of the large ribosomal RNA. Besides depurination of the rRNA, PAP has additional activities that contribute to its cytotoxicity. The mechanism of PAP cytotoxicity is summarized based on evidence from the analysis of transgenic plants and the yeast model system. PAP was initially found to be anti-viral when it was co-inoculated with plant viruses onto plants. Transgenic plants expressing PAP and non-toxic PAP mutants have displayed broad-spectrum resistance to both viral and fungal infection. The mechanism of PAP-induced disease resistance in transgenic plants is summarized.

The role of monocytes and T cells in 1,25-dihydroxyvitamin D3 mediated inhibition of B cell function in vitro

DEFF Research Database (Denmark)

Müller, K; Heilmann, C; Poulsen, L K

1991-01-01

1,25-Dihydroxyvitamin D3 (1,25-(OH)2D3) inhibits immunoglobulin production by human mononuclear cells (MNC) in vitro. The present study was undertaken to evaluate the role of T cells and monocytes in 1,25-(OH)2D3 induced suppression of B cell functions. The synthetic vitamin D3 analogue MC 903...... was examined in parallel. 1,25-(OH)2D3 and MC 903 showed a dose-related inhibition of IgM, IgG and IgA plaque-forming cells in poke-weed mitogen (PWM) activated cultures of MNC. This effect was most likely mediated through impairment of T cell and monocyte functions. First, the inhibitory effect was seen after...

Glycoprotein profiles of macrophages at different stages of activation as revealed by lectin binding after electrophoretic separation.

Science.gov (United States)

Irimura, T; North, S M; Nicolson, G L

1987-01-01

Glycoprotein profiles of rat macrophages (M phi) at different stages of activation were studied by examining the reactivity of various lectins to the glycoproteins separated by polyacrylamide gel electrophoresis. Ricinus communis agglutinin 1 (RCA1) revealed several components including glycoproteins of Mr 160 kDa and 65 kDa prominent in resident M phi. A pokeweed mitogen (PWM) isolectin, Pa-4, recognizes branched poly(N-acetyllactosamine)-type carbohydrate chains, and revealed a significant increase in glycoproteins of Mr ranging from 70 kDa to 150 kDa on thioglycolate-elicited M phi. Increased reactivity of PWM to thioglycolate-elicited M phi was observed by direct binding of 125I-labeled Pa-4 to intact or glutaraldehyde-fixed M phi. Histochemical staining of formaldehyde-fixed M phi in vitro with biotinylated Pa-4 was consistent with the gel analysis, that is, resident M phi had no reactivity while thioglycolate-elicited M phi showed slight reactivity. Alveolar and intratumoral M phi bound more Pa-4 than resident or thioglycolate-elicited M phi. The PWM isolectin may therefore serve as a marker for an early stage of M phi activation.

The pokeweed leaf mRNA transcriptome and its regulation by jasmonic acid.

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Kira C.M. Neller

2016-03-01

Full Text Available The American pokeweed plant, Phytolacca americana, is recognized for synthesizing pokeweed antiviral protein (PAP, a ribosome inactivating protein (RIP that inhibits the replication of several plant and animal viruses. The plant is also a heavy metal accumulator with applications in soil remediation. However, little is known about pokeweed stress responses, as large-scale sequencing projects have not been performed for this species. Here, we sequenced the mRNA transcriptome of pokeweed in the presence and absence of jasmonic acid (JA, a hormone mediating plant defense. Trinity-based de novo assembly of mRNA from leaf tissue and BLASTx homology searches against public sequence databases resulted in the annotation of 59 096 transcripts. Differential expression analysis identified JA-responsive genes that may be involved in defense against pathogen infection and herbivory. We confirmed the existence of several PAP isoforms and cloned a potentially novel isoform of PAP. Expression analysis indicated that PAP isoforms are differentially responsive to JA, perhaps indicating specialized roles within the plant. Finally, we identified 52 305 natural antisense transcript pairs, four of which comprised PAP isoforms, suggesting a novel form of RIP gene regulation. This transcriptome-wide study of a Phytolaccaceae family member provides a source of new genes that may be involved in stress tolerance in this plant. The sequences generated in our study have been deposited in the SRA database under project # SRP069141.

Roles of PU.1 in monocyte- and mast cell-specific gene regulation: PU.1 transactivates CIITA pIV in cooperation with IFN-gamma.

Science.gov (United States)

Ito, Tomonobu; Nishiyama, Chiharu; Nakano, Nobuhiro; Nishiyama, Makoto; Usui, Yoshihiko; Takeda, Kazuyoshi; Kanada, Shunsuke; Fukuyama, Kanako; Akiba, Hisaya; Tokura, Tomoko; Hara, Mutsuko; Tsuboi, Ryoji; Ogawa, Hideoki; Okumura, Ko

2009-07-01

Over-expression of PU.1, a myeloid- and lymphoid-specific transcription factor belonging to the Ets family, induces monocyte-specific gene expression in mast cells. However, the effects of PU.1 on each target gene and the involvement of cytokine signaling in PU.1-mediated gene expression are largely unknown. In the present study, PU.1 was over-expressed in two different types of bone marrow-derived cultured mast cells (BMMCs): BMMCs cultured with IL-3 plus stem cell factor (SCF) and BMMCs cultured with pokeweed mitogen-stimulated spleen-conditioned medium (PWM-SCM). PU.1 over-expression induced expression of MHC class II, CD11b, CD11c and F4/80 on PWM-SCM-cultured BMMCs, whereas IL-3/SCF-cultured BMMCs expressed CD11b and F4/80, but not MHC class II or CD11c. When IFN-gamma was added to the IL-3/SCF-based medium, PU.1 transfectant acquired MHC class II expression, which was abolished by antibody neutralization or in Ifngr(-/-) BMMCs, through the induction of expression of the MHC class II transactivator, CIITA. Real-time PCR detected CIITA mRNA driven by the fourth promoter, pIV, and chromatin immunoprecipitation indicated direct binding of PU.1 to pIV in PU.1-over-expressing BMMCs. PU.1-over-expressing cells showed a marked increase in IL-6 production in response to LPS stimulation in both IL-3/SCF and PWM-SCM cultures. These results suggest that PU.1 overproduction alone is sufficient for both expression of CD11b and F4/80 and for amplification of LPS-induced IL-6 production. However, IFN-gamma stimulation is essential for PU.1-mediated transactivation of CIITA pIV. Reduced expression of mast cell-related molecules and transcription factors GATA-1/2 and up-regulation of C/EBPalpha in PU.1 transfectants indicate that enforced PU.1 suppresses mast cell-specific gene expression through these transcription factors.

Testing of disease-resistance of pokeweed antiviral protein gene ...

African Journals Online (AJOL)

Transformation of pokeweed antiviral protein gene (PAP) into plants was shown to improve plant resistance to several viruses or fungi pathogens with no much negative effect on plant growth. The non-virulent defective PAP inhibits only the virus but does not interfere with the host. A non-virulent defective PAP gene ...

Human cord blood suppressor T lymphocytes. II. Characterization of inducer of suppressor cells

International Nuclear Information System (INIS)

Cheng, H.; Delespesse, G.

1986-01-01

Previously, we reported an antigen nonspecific inducer of T suppressor cell factor (TisF) produced by cord blood mononuclear cells (MNC) in 48-hr, two-way mixed lymphocyte cultures (MLC). The target of this factor was a radiosensitive, T4+ (T8-) adult suppressor T cell subset. The cellular origin of this TisF was examined in the present study. IgG production by pokeweed mitogen (PWM)-stimulated adult MNC was used as an assay for TisF activity. It was found that TisF-producing cells formed rosettes with sheep erythrocytes (E+) and were independent of adherent cells (AC) in the production of TisF. They were resistant to irradiation (2500 rads) and phenotypic characterization with T cell reactive monoclonal antibodies indicated that they resided in the T8- (T4+) population. Furthermore, both TQ1- and TQ1+ cells were required for the production of TisF activity and such activity could not be reconstituted by supernatants from TQ1- MLC and TQ1+ MLC. These results indicate that the production of TisF is dependent upon interactions between radioresistant E+, T8-, TQ1- and radioresistant E+, T8-, TQ1+ cells

Integration of the Pokeweed miRNA and mRNA Transcriptomes Reveals Targeting of Jasmonic Acid-Responsive Genes

Directory of Open Access Journals (Sweden)

Kira C. M. Neller

2018-05-01

Full Text Available The American pokeweed plant, Phytolacca americana, displays broad-spectrum resistance to plant viruses and is a heavy metal hyperaccumulator. However, little is known about the regulation of biotic and abiotic stress responses in this non-model plant. To investigate the control of miRNAs in gene expression, we sequenced the small RNA transcriptome of pokeweed treated with jasmonic acid (JA, a hormone that mediates pathogen defense and stress tolerance. We predicted 145 miRNAs responsive to JA, most of which were unique to pokeweed. These miRNAs were low in abundance and condition-specific, with discrete expression change. Integration of paired mRNA-Seq expression data enabled us to identify correlated, novel JA-responsive targets that mediate hormone biosynthesis, signal transduction, and pathogen defense. The expression of approximately half the pairs was positively correlated, an uncommon finding that we functionally validated by mRNA cleavage. Importantly, we report that a pokeweed-specific miRNA targets the transcript of OPR3, novel evidence that a miRNA regulates a JA biosynthesis enzyme. This first large-scale small RNA study of a Phytolaccaceae family member shows that miRNA-mediated control is a significant component of the JA response, associated with widespread changes in expression of genes required for stress adaptation.

Characterization and expression analysis of B Cell receptor accessory molecule CD79 gene in humphead snapper ( Lutjanus sanguineus)

Science.gov (United States)

Huang, Yucong; Yan, Xiuying; Cai, Shuanghu; Cai, Jia; Jian, Jichang; Lu, Yishan; Tang, Jufen; Wu, Zaohe

2016-04-01

CD79, a key component of the B cell antigen receptor complex, is composed of CD79α(Igα) and CD79β(Igβ) encoded by mb-1 and B29 respectively, and plays an important role in B cell signaling. In this study, we isolated and characterized mb-1 and B29 from humphead snapper ( Lutjanus sanguineus). Their tissue distribution and expression profiles after stimulations in vitro and in vivo were also investigated. The humphead snapper mb-1 and B29 contain open reading frames of 684 bp and 606 bp, encoding 227 amino acids and 201 amino acids, respectively. Both CD79α and CD79β possess signal peptide, extracellular Ig domain, transmembrane region and immunoreceptor tyrosine kinase activation motif (ITAM). Mb-1 is highly expressed in lymphoid organs (thymus, posterior kidney and spleen) and mucosal-associated lymphoid tissues (gill and intestine), while B29 is mainly detected in posterior kidney, spleen, gill and skin. Furthermore, transcription of mb-1 and B29 in head kidney leucocytes was up-regulated following lipopolysaccharide (LPS), pokeweed mitogen (PWM), and polyinosinic-polycytidylic acid (PolyI:C) stimulation, respectively, and their expression level in anterior kidney and spleen was also increased after challenged with formalin-inactived Vibrio harveyi. These results indicated that humphead snapper CD79 molecule might play an important role in immune response to pathogen infection.

Immunoglobulin production induced in vitro by glucocorticoid hormones: T cell-dependent stimulation of immunoglobulin production without B cell proliferation in cultures of human peripheral blood lymphocytes

International Nuclear Information System (INIS)

Grayson, J.; Dooley, N.J.; Koski, I.R.; Blaese, R.M.

1981-01-01

The direct effects of steroid hormones on the production of immunoglobulins and DNA synthesis by human T and B lymphocytes was evaluated in cultures of peripheral blood mononuclear cells. As detected by a reverse hemolytic plaque assay, the addition of 0.1 mM to 10 nM hydrocortisone to lymphocytes in culture in the absence of other stimulants or mitogens, resulted in the dramatic induction of immunoglobulin production with responses comparable to those seen in similar cultures stimulated with pokeweed mitogen. Steroid-stimulated immunoglobulin production was first seen after 48 h and peaked at 8-10 d of culture. The production of IgG, IgA, and IgM was induced following incubation with steroid. Glucocorticoids, but not estrogens or androgens, were capable of mediating this effect, and only compounds with affinity for the glucocorticoid receptor were active. The induction of immunoglobulin production was dependent on both T cells and monocytes; cultures depleted of either cell type did not produce immunoglobulin when stimulated with glucocorticoid hormones. Proliferation of B cells or T cells could not be detected by [/sup 3/H]thymidine incorporation or total cell recovery from steroid-stimulated cultures, even though such cultures demonstrated marked increases in immunoglobulin production. The mechanism responsible for this functional maturation of B cells to become high rate immunoglobulin producing cells is as yet undefined, although it appears to involve more than merely steroid mediated inactivation of suppressor T cells

Cellular kinetics in a patient with Sezary syndrome

International Nuclear Information System (INIS)

Chandra, P.; Chanana, A.D.; Chikkappa, G.; Cronkite, E.P.

1981-01-01

Cellular kinetics and proliferation of Sezary cells (SC) were studied in a 48-year-old woman with Sezary syndrome (SS). In vitro flash labeling indices of peripheral blood (PB) SC were studied by labeling with tritiated thymidine ( 3 HTdR) and tritiated cytidine ( 3 HCdR). Intradermal SC were labeled in vivo by local injection of 3 HTdR followed by skin biopsies of the injected sites. Traffic patterns of DNA labeled PB SC were studied by intravenous 3 HTdR followed by sampling of PB, skin, lymph node (LN), and bone marrow (BM). Fluxes of PB SC in various tissues were investigated by autotransfusion of 3 HCdR labeled PB SC followed by serial sampling of PB, LN, BM, and skin. In vitro response of PB SC to phytohemagglutinin (PHA), concanavalin A (Con A), and pokeweed (PWM) were also investigated. The results from these studies in this patient indicate that 1) proliferation of SC was primarily in the skin, 2) there was a negligible flux of SC from blood into skin, LN, and BM, and 3) the mitogenic response of PB mononuclear cells (mostly SC) to PHA, PWM, and Con A was poor

β-endorphin modulation of mitogen-stimulated calcium uptake by rat thymocytes

International Nuclear Information System (INIS)

Hemmick, L.M.; Bidlack, J.M.

1987-01-01

Lymphocytes stimulated by mitogens or antigens exhibit an enhanced calcium uptake early in the proliferation or activation response. Modulation of this calcium uptake results in alterations of proliferation and immunocompetence. β-endorphin and other opioids affect several parameters of lymphocyte competence. Limited data are available concerning the mechanism(s) of these effects. This study examines whether a possible opioid mechanism is the modification of the early calcium influx into stimulated lymphocytes. The time course of both concanavalin A (Con A) and phytohemagglutinin (PHA)-stimulated 45 Ca 2+ uptake into thymocytes was characterized to determine the optimal time for testing the effects of opioids. Β-Endorphin 1-31 significantly enhanced Con A-stimulated 45 Ca 2+ uptake into rat thymocytes. This peptide had no significant effect on PHA-simulated 45 Ca 2+ uptake or on basal thymocyte 45 Ca 2+ flux. The β/sub h/-endorphin stimulatory effect was titratable in the range of 0.1 nM to 10 μM. Naloxone did not reverse the enhancement. Met-enkephalinamide and other opioid agonists did not duplicate the stimulatory effect. Thus, the β/sub h/-endorphin 1-31 enhancement of Con A-stimulated 45 Ca 2+ uptake by rat thymocytes does not operate via classical opioid receptor mechanisms. β/sub h/-endorphin 1-31 appears to be acting on a subset of T cells that are responsive to Con A but not to PHA. 30 references, 4 figures, 1 table

Detection of proliferating cell nuclear antigens and interleukin-2 beta receptor molecules on mitogen- and antigen-stimulated lymphocytes.

Science.gov (United States)

Hesketh, J; Dobbelaere, D; Griffin, J F; Buchan, G

1993-01-01

The expression of interleukin-2 receptors (IL-2R) and proliferating cell nuclear antigens (PCNA) were compared for their usefulness as markers of lymphocyte activation. Heterologous polyclonal (anti-bovine IL-2R) and monoclonal (anti-human PCNA) antibodies were used to detect the expression of these molecules on activated deer lymphocytes. Both molecules were co-expressed on blast cells which had been activated with mitogen [concanavalin A (Con A)]. There was detectable up-regulation of IL-2R expression in response to antigen [Mycobacterium bovis-derived purified protein derivative (PPD)] stimulation while PCNA expression mimicked lymphocyte transformation (LT) reactivity. PCNA expression was found to more accurately reflect both antigen- and mitogen-activated lymphocyte activation, as estimated by LT activity. The expression of PCNA was used to identify antigen reactive cells from animals exposed to M. bovis. A very low percentage (1.1 +/- 0.4%) of peripheral blood lymphocytes from non-infected animals could be stimulated to express PCNA by in vitro culture with antigen (PPD). Within the infected group both diseased and healthy, 'in-contact', animals expressed significantly higher levels of PCNA upon antigen stimulation. PMID:8104884

beta. -endorphin modulation of mitogen-stimulated calcium uptake by rat thymocytes

Energy Technology Data Exchange (ETDEWEB)

Hemmick, L.M.; Bidlack, J.M.

1987-10-19

Lymphocytes stimulated by mitogens or antigens exhibit an enhanced calcium uptake early in the proliferation or activation response. Modulation of this calcium uptake results in alterations of proliferation and immunocompetence. ..beta..-endorphin and other opioids affect several parameters of lymphocyte competence. Limited data are available concerning the mechanism(s) of these effects. This study examines whether a possible opioid mechanism is the modification of the early calcium influx into stimulated lymphocytes. The time course of both concanavalin A (Con A) and phytohemagglutinin (PHA)-stimulated /sup 45/Ca/sup 2 +/ uptake into thymocytes was characterized to determine the optimal time for testing the effects of opioids. BETA-Endorphin 1-31 significantly enhanced Con A-stimulated /sup 45/Ca/sup 2 +/ uptake into rat thymocytes. This peptide had no significant effect on PHA-simulated /sup 45/Ca/sup 2 +/ uptake or on basal thymocyte /sup 45/Ca/sup 2 +/ flux. The ..beta../sub h/-endorphin stimulatory effect was titratable in the range of 0.1 nM to 10 ..mu..M. Naloxone did not reverse the enhancement. Met-enkephalinamide and other opioid agonists did not duplicate the stimulatory effect. Thus, the ..beta../sub h/-endorphin 1-31 enhancement of Con A-stimulated /sup 45/Ca/sup 2 +/ uptake by rat thymocytes does not operate via classical opioid receptor mechanisms. ..beta../sub h/-endorphin 1-31 appears to be acting on a subset of T cells that are responsive to Con A but not to PHA. 30 references, 4 figures, 1 table.

Relations between the stimulation of mixed lymphocyte populations and the staging system according Rai in patients with chronic lymphatic leukemia

International Nuclear Information System (INIS)

Heilmann, E.; Venne, U.

1979-01-01

By means of the incorporation rate of 3 H thymidine into the lymphocytes of patients with chronic lymphatic leukemia the possibility of stimulating them by using different mitogens was checked and compared with normal persons. The examination covered 11 patients treated with extracorporeal irradiation of the blood (ECIB), 5 patients treated with a chlorambucil therapy, and 10 untreated patients who where classified according to the staging system proposed by Rai. The lymphocytes of the peripheral blood were stimulated as mixed and isolated T and B-lymphocytes in the microculture by using the mitogens PHA, PWM, ConA, and LPS. In all CLL patients there was a diminished stimulation rate of a mixed lymphocyte population. A relation existed between the seriousness of the stage and the deminution of the incorporation rate of 3 H thymidine. A corresponding correlation could not be identified in untreated CLL patients. Isolated T-lymphocytes revealed better results of stimulation than the total population. As to their function B-lymphocytes showed a dependence on the kind of therapy. In the mixed lymphocyte culture of normal persons the best findings could be observed after stimulation with PHA, that is also valid for CLL patients. PHA, PWA, ConA, and LPS were suitable as substances stimulating B-lymphocytes with different efficacy in normal persons and CLL patients. Both collectives showed the best results in the T-lymphocyte culture after stimulation with LPS. (author)

Large-signal stability analysis of PWM converters

Energy Technology Data Exchange (ETDEWEB)

Huynh, P.T. [Philips Labs., Briarcliff Manor, NY (United States); Cho, B.H. [Seoul National Univ. (Korea, Republic of). Dept. of Electrical Engineering

1995-12-31

Investigation of the effects of existing nonlinearities on the stability of PWM converters is performed. The bilinear structure, the duty cycle saturation, and the opamp saturation are the principal nonlinearities in PWM converters. These nonlinearities are incorporated in the large-signal analytical models of PWM converters, and the basic input-output stability theory is applied to analyze their stability. Design and optimization of the small-signal loop gains to counteract the undesirable nonlinear effects are also discussed.

Effect of monoclonal antibodies (MoAb) to class I and class II HLA antigens on lectin- and MoAb OKT3-induced lymphocyte proliferation.

Science.gov (United States)

Akiyama, Y; Zicht, R; Ferrone, S; Bonnard, G D; Herberman, R B

1985-04-01

We have examined the effect of several monoclonal antibodies (MoAb) to monomorphic determinants of class II HLA antigens, and MoAb to monomorphic determinants of class I HLA antigens and to beta-2-microglobulin (beta 2-mu) on lectin- and MoAb OKT3-induced proliferation of human peripheral blood mononuclear cells (PBMNC) and cultured T cells (CTC). Some, but not all, anti-class II HLA MoAb inhibited the proliferative response of PBMNC to MoAb OKT3 and pokeweed mitogen (PWM). The degree of inhibitory effect varied considerably. This effect was not limited to anti-class II HLA MoAb since anti-class I HLA MoAb and anti-beta 2-mu MoAb also inhibited MoAb OKT3- or PWM-induced proliferative responses. In contrast, the response of PBMNC to phytohemagglutinin (PHA) and concanavalin A (Con A) was not blocked by any anti-class II HLA MoAb. However, some anti-class II HLA MoAb also inhibited the proliferative response of CTC plus allogeneic peripheral blood adherent accessory cells (AC) to PHA or Con A as well as to MoAb OKT3 or PWM. This may be attributable to the substantially greater class II HLA antigen expression by CTC than by fresh lymphocytes. Pretreatment of either CTC or AC with anti-class II HLA MoAb inhibited OKT3-induced proliferation. In contrast, pretreatment of CTC, but not AC, with anti-class I HLA MoAb inhibited the proliferative response of CTC to OKT3. Pretreatment of CTC with anti-class I HLA MoAb inhibited PHA-, Con A and PWM-induced proliferation, to a greater degree than the anti-class II HLA MoAb. It appears as if lymphocyte activation by different mitogens exhibits variable requirements for the presence of cells expressing major histocompatibility determinants. Binding of Ab to membrane markers may interfere with lymphocyte-AC cooperation, perhaps by inhibiting binding of mitogens to their receptors or by interfering with lymphocyte and AC function. We also have examined the role of class II HLA antigens on CTC by depleting class II HLA-positive cells

Windowed SHE-PWM of Interleaved Four-Quadrant Converters for Resonance Suppression in Traction Power Supply Systems

DEFF Research Database (Denmark)

Song, Kejian; Konstantinou, Georgios; Mingli, Wu

2017-01-01

AC electric locomotives that use a number of interleaved four-quadrant converters generate high-frequency switching harmonics which may stimulate certain resonances in traction power supply systems (TPSSs). A windowed selective harmonic elimination pulse-width modulation (SHE-PWM) method...

Carbohydrate metabolism of lymphocytes: modified methodology and comparisons of diabetics with non-diabetics

International Nuclear Information System (INIS)

Glassman, A.B.; Bennett, C.E.

1980-01-01

Changes in the hexose monophosphate shunt (HMPS) and Krebs cycle activity during lymphocyte blast transformation are reported in 50 patients with diabetes mellitus and 50 non-diabetics. A modified technique using 12 X 75 mm sterile tubes and micropipette tips stuffed with filter paper was used. The filter paper, soaked with hyamine hydroxide, absorbed radioactively labeled CO 2 produced from [ 14 C]- labeled glucose incorporated by cells. [ 14 C]CO 2 from glucose labeled at the C-1 position measured the activity of the HMPS. [ 14 C]CO 2 from glucose labeled at the C-2 position measured the HMPS activity associated with the feedback of pentose sugars. [ 14 C]-labeled CO 2 from glucose labeled at the C-6 position was used to measure Krebs cycle activity. A statistically significant decrease in HMPS activity was found in diabetic cells exposed to the mitogens phytohemagglutinin-P (PHA-P), concanavalin-A (CON-A) and pokeweed mitogen (PWM) (P<0.01). This decrease in HMPS activity and its relation to lymphocyte blast transformation may be related to the increased incidence of infection known to occur in patients with diabetes mellitus. (Auth.)

Carbohydrate metabolism of lymphocytes: modified methodology and comparisons of diabetics with non-diabetics

Energy Technology Data Exchange (ETDEWEB)

Glassman, A B; Bennett, C E [Medical University of South Carolina, Charleston, SC, (USA). Department of Laboratory Medicine

1980-10-01

Changes in the hexose monophosphate shunt (HMPS) and Krebs cycle activity during lymphocyte blast transformation are reported in 50 patients with diabetes mellitus and 50 non-diabetics. A modified technique using 12 X 75 mm sterile tubes and micropipette tips stuffed with filter paper was used. The filter paper, soaked with hyamine hydroxide, absorbed radioactively labeled CO/sub 2/ produced from (/sup 14/C)- labeled glucose incorporated by cells. (/sup 14/C)CO/sub 2/ from glucose labeled at the C-1 position measured the activity of the HMPS. (/sup 14/C)CO/sub 2/ from glucose labeled at the C-2 position measured the HMPS activity associated with the feedback of pentose sugars. (/sup 14/C)-labeled CO/sub 2/ from glucose labeled at the C-6 position was used to measure Krebs cycle activity. A statistically significant decrease in HMPS activity was found in diabetic cells exposed to the mitogens phytohemagglutinin-P (PHA-P), concanavalin-A (CON-A) and pokeweed mitogen (PWM) (P<0.01). This decrease in HMPS activity and its relation to lymphocyte blast transformation may be related to the increased incidence of infection known to occur in patients with diabetes mellitus.

Distortion-Free 1-Bit PWM Coding for Digital Audio Signals

Directory of Open Access Journals (Sweden)

John Mourjopoulos

2007-01-01

Full Text Available Although uniformly sampled pulse width modulation (UPWM represents a very efficient digital audio coding scheme for digital-to-analog conversion and full-digital amplification, it suffers from strong harmonic distortions, as opposed to benign non-harmonic artifacts present in analog PWM (naturally sampled PWM, NPWM. Complete elimination of these distortions usually requires excessive oversampling of the source PCM audio signal, which results to impractical realizations of digital PWM systems. In this paper, a description of digital PWM distortion generation mechanism is given and a novel principle for their minimization is proposed, based on a process having some similarity to the dithering principle employed in multibit signal quantization. This conditioning signal is termed “jither” and it can be applied either in the PCM amplitude or the PWM time domain. It is shown that the proposed method achieves significant decrement of the harmonic distortions, rendering digital PWM performance equivalent to that of source PCM audio, for mild oversampling (e.g., ×4 resulting to typical PWM clock rates of 90 MHz.

Distortion-Free 1-Bit PWM Coding for Digital Audio Signals

Directory of Open Access Journals (Sweden)

Mourjopoulos John

2007-01-01

Full Text Available Although uniformly sampled pulse width modulation (UPWM represents a very efficient digital audio coding scheme for digital-to-analog conversion and full-digital amplification, it suffers from strong harmonic distortions, as opposed to benign non-harmonic artifacts present in analog PWM (naturally sampled PWM, NPWM. Complete elimination of these distortions usually requires excessive oversampling of the source PCM audio signal, which results to impractical realizations of digital PWM systems. In this paper, a description of digital PWM distortion generation mechanism is given and a novel principle for their minimization is proposed, based on a process having some similarity to the dithering principle employed in multibit signal quantization. This conditioning signal is termed "jither" and it can be applied either in the PCM amplitude or the PWM time domain. It is shown that the proposed method achieves significant decrement of the harmonic distortions, rendering digital PWM performance equivalent to that of source PCM audio, for mild oversampling (e.g., resulting to typical PWM clock rates of 90 MHz.

Effect of chloroquine on human lymphocyte proliferation

DEFF Research Database (Denmark)

Bygbjerg, Ib Christian; Flachs, H

1986-01-01

The effect of chloroquine on human blood mononuclear cells was studied. High concentrations of chloroquine in vitro profoundly suppressed the proliferation of mitogen- and antigen-stimulated cells, as indicated by decreased 14C-thymidine incorporation. Lower concentrations of chloroquine increase...... to large particulate antigens; the response to small antigens was not affected. The mode of action of chloroquine and the possible consequences of the findings for dosage of chloroquine when used for malaria prophylaxis is discussed.......The effect of chloroquine on human blood mononuclear cells was studied. High concentrations of chloroquine in vitro profoundly suppressed the proliferation of mitogen- and antigen-stimulated cells, as indicated by decreased 14C-thymidine incorporation. Lower concentrations of chloroquine increased...... the response to pokeweed mitogen. The response to concanavalin A and to various antigens was suppressed, especially the response to large particulate antigens. Oral intake of 300 mg of chloroquine base/week did not affect the lymphocyte proliferative responses. 600 mg of base/week decreased the response...

The anti-proliferative effect of cation channel blockers in T lymphocytes depends on the strength of mitogenic stimulation.

Science.gov (United States)

Petho, Zoltan; Balajthy, Andras; Bartok, Adam; Bene, Krisztian; Somodi, Sandor; Szilagyi, Orsolya; Rajnavolgyi, Eva; Panyi, Gyorgy; Varga, Zoltan

2016-03-01

Ion channels are crucially important for the activation and proliferation of T lymphocytes, and thus, for the function of the immune system. Previous studies on the effects of channel blockers on T cell proliferation reported variable effectiveness due to differing experimental systems. Therefore our aim was to investigate how the strength of the mitogenic stimulation influences the efficiency of cation channel blockers in inhibiting activation, cytokine secretion and proliferation of T cells under standardized conditions. Human peripheral blood lymphocytes were activated via monoclonal antibodies targeting the TCR-CD3 complex and the co-stimulator CD28. We applied the blockers of Kv1.3 (Anuroctoxin), KCa3.1 (TRAM-34) and CRAC (2-Apb) channels of T cells either alone or in combination with rapamycin, the inhibitor of the mammalian target of rapamycin (mTOR). Five days after the stimulation ELISA and flow cytometric measurements were performed to determine IL-10 and IFN-γ secretion, cellular viability and proliferation. Our results showed that ion channel blockers and rapamycin inhibit IL-10 and IFN-γ secretion and cell division in a dose-dependent manner. Simultaneous application of the blockers for each channel along with rapamycin was the most effective, indicating synergy among the various activation pathways. Upon increasing the extent of mitogenic stimulation the anti-proliferative effect of the ion channel blockers diminished. This phenomenon may be important in understanding the fine-tuning of T cell activation. Copyright © 2016 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.

Analisis Harmonisa Inverter PWM Satu Fasa

OpenAIRE

Rejeki Simanjorang

2008-01-01

Pada tesis ini dianalisis harmonisa inverter PWM satu fasa. Inverter PWM satu fasa yang akan ditinjau adalah inverter satu fasa jembatan penuh (konvensional) dan inverter komposit. Analisis difokuskan pada penentuan pola penyaklaran yang optimum agar pembangkitan harmonisa dan switching losses inverter rendah. Untuk menentukan pola penyaklaran optimum maka dilakukan analisis yang berbasis pada rangkaian ekivalen harmonisa inverter satu fasa. Dengan menggunakan pola penyaklaran optimum, kedua ...

A new Zero-Current-Transition PWM switching cell

Energy Technology Data Exchange (ETDEWEB)

Grigore, V. [Electronics and Telecommunications Faculty, `Politechnica` University Bucharest (Romania); Kyyrae, J. [Helsinki University of Technology, Otaniemi (Finland): Institute of Intelligent Power Electronics

1997-12-31

In this paper a new Zero-Current-Transition (ZCT) PWM switching cell is presented. The proposed switching cell is composed of the normal hard-switched PWM cell (consisting of one active switch and one passive switch), plus as auxiliary circuit. The auxiliary circuit is inactive during the ON ad OFF intervals of the switches in the normal PWM switch. The transitions between the two states are controlled by the auxiliary circuit. Prior to turn-off, the current through the active switch in the PWM cell is forced to zero, thus the turn-off losses of the active switch are practically eliminated. At turn-on the auxiliary circuit slows down the growing rate of the current through the main switch. Thus, turn-on losses are also very much reduced. The active switch operates under ZCT conditions, the passive switch (diode) has a controlled reverse recovery, while the switch in the auxiliary circuit operates under Zero-Current-Switching (ZCS) conditions. (orig.) 3 refs.

Color adjustable LED driver design based on PWM

Science.gov (United States)

Du, Yiying; Yu, Caideng; Que, Longcheng; Zhou, Yun; Lv, Jian

2012-10-01

Light-emitting diode (LED) is a liquid cold source light source that rapidly develops in recent years. The merits of high brightness efficiency, long duration, high credibility and no pollution make it satisfy our demands for consumption and natural life, and gradually replace the traditional lamp-house-incandescent light and fluorescent light. However, because of the high cost and unstable drive circuit, the application range is restricted. To popularize the applications of the LED, we focus on improving the LED driver circuit to change this phenomenon. Basing on the traditional LED drive circuit, we adopt pre-setup constant current model and introduce pulse width modulation (PWM) control method to realize adjustable 256 level-grays display. In this paper, basing on human visual characteristics and the traditional PWM control method, we propose a new PWM control timing clock to alter the duty cycle of PWM signal to realize the simple gamma correction. Consequently, the brightness can accord with our visual characteristics.

A New parallel Resonant DC-Link Inverter for Soft Switched PWM

Energy Technology Data Exchange (ETDEWEB)

Cho, J G; Kim, H S; Cho, G H [Korea Advanced Energy Research Inst., Daeduk-Danji (Korea, Republic of). Korea Nuclear Safety Center

1993-03-01

A novel soft switching PWM converter for high frequency AC/DC power conversion is presented by using a new parallel resonant dc-link(PRDCL) and by adopting single phase soft switching(SPSS) technique. The new PRDCL provides variable link pulse position as well as variable link pulse width, which is quite different feature from the other resonant dc-links and thus the PWM capability can be remarkably increased. The SPSS technique is also adopted for further enhancement of PWM capability. Moderate combination of two soft switching operations enables the conventional space vector PWM technique to be used. Due to distinctive advantages including true PWM capability, minimum device voltage stresses(all Vs) and reasonable additional device count(3 devices), the proposed converter can be operated in a wide power range(20-200 KW). Operational principles, analyses and the realization of a space vector PWM of the proposed converter are presented. Simulation results are also shown to verify the operational principle. (author). 15 refs., 14 figs.

Logo2PWM: a tool to convert sequence logo to position weight matrix.

Science.gov (United States)

Gao, Zhen; Liu, Lu; Ruan, Jianhua

2017-10-03

position weight matrix (PWM) and sequence logo are the most widely used representations of transcription factor binding site (TFBS) in biological sequences. Sequence logo - a graphical representation of PWM, has been widely used in scientific publications and reports, due to its easiness of human perception, rich information, and simple format. Different from sequence logo, PWM works great as a precise and compact digitalized form, which can be easily used by a variety of motif analysis software. There are a few available tools to generate sequence logos from PWM; however, no tool does the reverse. Such tool to convert sequence logo back to PWM is needed to scan a TFBS represented in logo format in a publication where the PWM is not provided or hard to be acquired. A major difficulty in developing such tool to convert sequence logo to PWM is to deal with the diversity of sequence logo images. We propose logo2PWM for reconstructing PWM from a large variety of sequence logo images. Evaluation results on over one thousand logos from three sources of different logo format show that the correlation between the reconstructed PWMs and the original PWMs are constantly high, where median correlation is greater than 0.97. Because of the high recognition accuracy, the easiness of usage, and, the availability of both web-based service and stand-alone application, we believe that logo2PWM can readily benefit the study of transcription by filling the gap between sequence logo and PWM.

Enhancement of cell-cell contact by a nonmitogenic lectin increases blastogenic response and IL-2 release by mitogen-stimulated mouse thymocytes.

Science.gov (United States)

Favero, J; Marti, J; Dornand, J; Bonnafous, J C; Mani, J C

1986-03-01

We have examined the influence of peanut agglutinin (PNA), a lectin which agglutinates but does not stimulate mouse thymocytes, on the responsiveness of these cells to concanavalin A (Con A) or galactose oxidase stimulation. Binding low amounts of PNA on unseparated mouse thymocytes pretreated with neuraminidase highly enhances the mitogenic response and the level of interleukin 2 release in the culture medium upon Con A stimulation. We have shown that PNA present on the cell surface acts as a crosslinking agent which favors intercellular binding between accessory cells (macrophages) and thymocytes, leading through this enhanced cooperation by cell-cell contact to an enhanced blastogenic response.

A new Zero-Voltage-Transition PWM switching cell

Energy Technology Data Exchange (ETDEWEB)

Grigore, V. [Electronics and Telecommunications Faculty `Politebuica` University Bucharest (Romania); Kyyrae, J. [Helsinki University of Technology, Otaniemi (Finland): Institute of Intelligent Power Electronics

1997-12-31

In this paper a new Zero-Voltage-Transition (ZVT) PWM switching cell is presented. The proposed switching cell is composed of the normal hard-switched PWM cell (consisting of one active switch and one passive switch), plus an auxiliary circuit (consisting of one active switch and some reactive components). The auxiliary circuit is inactive during the ON and OFF intervals of the switches in the normal PWM switch. However, the transitions between the two states are controlled by the auxiliary circuit. Prior to turn-on, the voltage across the active switch in the PWM cell is forced to zero, thus the turn-on losses of the active switch are practically eliminated. At turn-off the auxiliary circuit behaves like a non-dissipative passive snubber reducing the turn-off losses to a great extent. Zero-Voltage-Transition switching technique almost eliminates switching losses. The active switch operates under ZVT conditions, the passive switch (diode) has a controlled reverse recovery, and the switch in the auxiliary circuit operates under Zero-Current-Switching (ZCS) conditions. (orig.) 6 refs.

Realise of PWM-generating based on FPGA

International Nuclear Information System (INIS)

Su Rongfeng; Xu Ruinian; Huang Maomao

2012-01-01

The power supply digital controllers of Shanghai Synchrotron Radiation Facility(SSRF) make use of the PWM (pulse width modulation) wave as the feedback to the power-electrical devices, so as to obtain constant current of high accuracy and stability. The design of PWM wave generation structure in FPGA is good for a compact controller,and the reduction of the usage of Integrated Circuits (ICs) decreases the interference from the noise among the ICs, hence better performance of the controller. In addition, FPGA can be programmed circularly at any time,so as to optimize the structure design and make a maximum use of the advantage of FPGA. As a part of transplanting the complete function of the DSP (digital signal processor/processing), realizing the generation of PWM wave in FPGA is feasible. In this paper, we report progress in this regard at SSRF. (authors)

B and T lymphocytes in man. I. Effect of infant thymic irradiation on the circulating B and T lymphocytes

International Nuclear Information System (INIS)

Reddy, M.M.; Goh, K.; Hempelmann, L.H.

1976-01-01

B and T lymphocytes were studied in a group of adults whose thymic glands were irradiated in infancy for alleged thymic enlargement. Two independent methods were used to determine the B and T lymphocytes from each peripheral blood specimen: (1) the relative proportion of cells with surface immunoglobulins (B lymphocytes) and cells forming rosettes with sheep erythrocytes (T lymphocytes); and (2) the relative mitogenic response to phytohemagglutinin (T lymphocytes) and to pokeweed mitogen (B lymphocytes). All specimens were coded. The results obtained indicate: (1) a reduction of B and T lymphocytes; and (2) a decreased mitogenic response of lymphocytes to phytohemagglutinin and pokeweed mitogen in this group of patients as compared with the controls. These observations suggest that (1) the effect of irradiation to the thymus gland on lymphocytes is long lasting and (2) both B and T lymphocytes are affected by irradiation to the thymus gland

Functional studies on lymphocytes from two siblings with congential hypogammaglobulinaemia

International Nuclear Information System (INIS)

Tauris, P.; Wendelboe Hansen, P.

1983-01-01

Two brothers with hypogammaglobulinaemia classified as common variable immunodeficiency (CVID) were investigated for distribution of pheripheral blood lymphocyte (PBL) subpopulations, DNA synthesis and plaque-forming cell (PFC) capability of pokeweed mitogen (PWM) activated autologous and allogenic cocultures. Both patients had a decreased absolute number of T cells and normal or elevated levels of surface immunoglobulin (SmIg) bearing cells. Isolated B cells cocultured with autologous or allogeneic 4000 r irradiated T cells responded subnormally to PWM monitored by the 3 H-thymidine incorporation in microcultures whereas B cells cocultured with allogeneic untreated normal T cells proliferated normally. PBL from parallel macrocultures of unfractionated or T/B separated patients' cells were not able to produce plaques using a reversed haemolytic protein A assay. Addition of glucocorticoid to unfractionated PBL did not reverse the unresponsiveness. In allogeneic cocultures patients' untreated or 2000 r irradiated T cells induced a normal PFC response. Normal untreated T cells induced a reduced number of IgM- and IgG-PFC from patients' B cells but this response was almost eliminated using irradiated normal T cells. These results demonstrate a primary B cell defect in the patients and indicate an impaired cooperation between patients' B and T cells. Activation of patients' B cells to Ig secretion requires the presence of proliferating T cells. (author)

A unified triangle carrier based PWM strategy for three-phase N-level diode clamped inverters

DEFF Research Database (Denmark)

Li, Kai; Xie, Chuan; Wei, Min

2017-01-01

The triangle carrier based pulse width modulation (TCB-PWM) can be functionally equivalent to space vector base PWM (SVB-PWM). For multi-level inverter, it is very difficult to realize the SVB-PWM because its vector space is very complex. In this paper, a unified TCB-PWM strategy for three-phase ...

Cytokine production by porcine mononuclear leukocytes stimulated by mitogens

Czech Academy of Sciences Publication Activity Database

Rašková, G.; Kovářů, František; Bártová, J.

2005-01-01

Roč. 74, - (2005), s. 521-525 ISSN 0001-7213 R&D Projects: GA ČR GA524/05/0267 Institutional research plan: CEZ:AV0Z50450515 Keywords : cytokine * ELISpot * mitogen Subject RIV: ED - Physiology Impact factor: 0.353, year: 2005

Reduced response of splenocytes after mitogen-stimulation in the prion protein (PrP) gene-deficient mouse: PrPLP/Doppel production and cerebral degeneration

International Nuclear Information System (INIS)

Kim, Chi-Kyeong; Hirose, Yuko; Sakudo, Akikazu; Takeyama, Natsumi; Kang, Chung-Boo; Taniuchi, Yojiro; Matsumoto, Yoshitsugu; Itohara, Shigeyoshi; Sakaguchi, Suehiro; Onodera, Takashi

2007-01-01

Splenocytes of wild-type (Prnp +/+ ) and prion protein gene-deficient (Prnp -/- ) mice were treated with various activation stimuli such as T cell mitogen concanavalin A (ConA), phorbol 12-myristate 13-acetate (PMA) + ionomycin (Io), or B cell mitogen lipopolysaccharide (LPS). Cellular prion protein (PrP C ) expression was enhanced following ConA stimulation, but not PMA + Io or LPS in Prnp +/+ splenocytes. Rikn Prnp -/- splenocytes elicited lower cell proliferations than Prnp +/+ or Zrch I Prnp -/- splenocytes after LPS stimulation and showed sporadic nerve cells in the cerebral cortex and deeper structure. Around the degenerated nerve cells, mild vacuolation in the neuropil was observed. This neural alteration correlated well to the suppressed response of B cells in the spleen. The finding that discrete lesions within the central nervous systems induced marked modulation of immune function probably indicates the existence of a delicately balanced neural-endocrine network by PrP C and PrPLP/Doppel

Pengaruh Penambahan PWM (Pulse Width Modulation Pada Generator HHO Tipe Dry Cell

Directory of Open Access Journals (Sweden)

Fungky Dyan Pertiwi

2013-09-01

Full Text Available Generator HHO memanfaatkan proses elektrolisis air agar mendapatkan gas H2. Namun, pada praktiknya pemakaian arus dari aki yang besar dan temperatur tinggi membuat bejana generator menjadi cepat rusak, sehingga dibutuhkan tambahan rangkaian elektronika PWM pada pengujian generator HHO guna mengatasi permasalahan tersebut. Penelitian menggunakan elektroda plat berjumlah 9 berdimensi 120mm 120mm, tebal 1mm dan dibatasi oleh o-ring dengan diameter 126mm, tebal 3mm. Pengujian dilakukan secara eksperimen dengan 2 kelompok yaitu kelompok control yang mana pengujian tanpa menggunakan PWM serta kelompok uji dimana pengujian menggunakan PWM dengan variasi duty cycle 30%, 50% dan 70%. Pengujian dilakukan hingga temperatur elektrolit 93oC. Hasil uji didapatkan bahwa arus, laju produksi dan efisiensi terbesar didapatkan pada pengujian tanpa PWM yang mencapai 60,6A, 6,033 10-6kg/s dan 25,69%. Namun, pada pengambilan data kedua efisiensi turun menjadi 19,74%. Penambahan PWM pada pengujian berpengaruh pada arus dan temperatur yang stabil meskipun laju produksi dan efisiensi lebih kecil daripada pengujian tanpa PWM. Pengujian dengan PWM pada duty cycle 70% menghasilkan laju produksi dan efisiensi terbesar yang mencapai 1,843 10-6 kg/s dan 15,19%.

PWM CONTROLLER'S MODELS FOR INVESTIGATION ACS IN SPICEFAMILY ECAD PROGRAMS

Directory of Open Access Journals (Sweden)

O. V. VASYLENKO

2018-05-01

Full Text Available Purpose. To improve simulation and design of Automatic Control Systems in the SPICE-compatible programs and to obtain separate economic and universal macromodels of PWM controller. Development of an PWM controller economical macromodel for the study of automatic control systems (ACS in computer-aided design (ECAD  programs, which does not generate algorithmic failures in comparison with the existing models of PWM. Findings. Analysis of SPICE-family applications’ mathematical basis allowed to classifying existing models of PWM-controllers, defining their suitability for ACS simulation. The criteria for the synthesis of new models have been defined. For the SPICE 3G algorithms, the Switch and Averaged models based on behavioral elements has been developed. Universal and economical PWM controller macromodel based on the simple algorithm for determining the output signal with minimum numbers of input parameters has been designed. For the Automated Measuring magnetic susceptibility System, the macromodel of quasi-PWM signal generator have been designed, which is used in the compensation subsystem. This model is different from the existing ones: it synthesizes the staircase output signal instead the pulse one, thus, there is direct control of the amplitude of the output signal, which is taken averaged. The adequacy of the models is confirmed as comparison of the simulation results during investigations of the model already existing in the SPICE program, as well as the results of experiments with real ACS. The modeling of the PWM controller was carried out on the basis of behavioral elements from the ECAD library, simulation (solution of algebra-differential equations systems with programming elements is based on SPICE algorithms. The object of the study was the simulation process of ACS with the pulse-width principle of adjusting the output value. The subject of the research are the models of PWM controllers. Originality. The new macromodel of PWM

Novel Cell Preservation Technique to Extend Bovine In Vitro White Blood Cell Viability.

Directory of Open Access Journals (Sweden)

Emilie L Laurin

Full Text Available Although cell-mediated immunity based diagnostics can be integral assays for early detection of various diseases of dairy cows, processing of blood samples for these tests is time-sensitive, often within 24 hours of collection, to maintain white blood cell viability. Therefore, to improve utility and practicality of such assays, the objective of this study was to assess the use of a novel white blood cell preservation technology in whole bovine blood. Blood samples from ten healthy cows were each divided into an unpreserved control sample and a test sample preserved with commercially-available cell transport medium. Samples were maintained at room temperature and stimulated with the mitogens pokeweed and concanavalinA, as well as with interleukin-12 p40. Stimulation was completed on days 1, 5, and 8 post-sampling. Viability of white blood cells was assessed through interferon gamma production determined with a commercial enzyme linked immunosorbent assay. In addition, mononuclear cell viability was assessed with propidium iodide flow cytometry. Greater interferon gamma production was observed on days 5 and 8 post-collection in preserved samples, with both pokeweed and concanavalinA stimulating positive interferon gamma production on day 5 post-collection. A greater proportion of the amount of interferon gamma produced on day 1 continued to be produced on days 5 and 8 post-collection with concanavalinA stimulation (with or without interleukin 12 as compared to pokeweed stimulation. Additionally, viable mononuclear cells were still present at eight days post-collection, with a higher mean proportion detected at days 5 and 8 in all stimulated preserved samples. This practical and simple method to extend in vitro white blood cell viability could benefit the efficient utilization of cell-based blood tests in ruminants.

Soft-switching PWM full-bridge converters topologies, control, and design

CERN Document Server

Ruan, Xinbo

2014-01-01

Soft-switching PWM full-bridge converters have been widely used in medium-to-high power dc-dc conversions for topological simplicity, easy control and high efficiency. Early works on soft-switching PWM full-bridge converter by many researchers included various topologies and modulation strategies.  However, these works were scattered, and the relationship among these topologies and modulation strategies had not been revealed. This book intends to describe systematically the soft-switching techniques for pulse-width modulation (PWM) full-bridge converters, including the topologies, control and

In vitro induction of lymphocyte responsiveness by a Strongylus vulgaris-derived mitogen.

Science.gov (United States)

Bailey, M; Lloyd, S; Martin, S C; Soulsby, E J

1984-01-01

Proliferation in vitro of peripheral blood lymphocytes both from horses infected with Strongylus vulgaris and from helminth-free ponies was observed in the presence of extracts of the fourth and fifth stage larvae and adults of S. vulgaris. In addition, S. vulgaris extracts induced transformation in cultures of peripheral blood lymphocytes from sheep and dogs and in mouse spleen cell cultures. Nylon wool non-adherent, T cell enriched fractions of lymphocytes from both mice and horses were stimulated by the S. vulgaris larval mitogen while no proliferation was observed in cultures containing nylon wool adherent, B cell enriched fractions. Macrophage co-operation appeared not to be necessary for S. vulgaris mitogen-induced transformation of spleen cells. The S. vulgaris mitogen stimulated a subpopulation of mouse spleen cells different from those responsive to PHA, Con A and LPS. These cells might be T helper cells since B cells were stimulated to proliferate in the presence of both T cells and S. vulgaris larval mitogen. In addition, the supernatant of in vitro cultured larvae of S. vulgaris induced slight, but significant transformation of equine peripheral blood lymphocytes. Therefore, it is possible that the S. vulgaris mitogen released by both viable parasites and degenerating larvae might induce T cell dependent production of immunoglobulin in vivo and account for the beta-globulinaemia, of which IgG(T) is a major component, in S vulgaris infected horses.

Transistorized PWM inverter-induction motor drive system

Science.gov (United States)

Peak, S. C.; Plunkett, A. B.

1982-01-01

This paper describes the development of a transistorized PWM inverter-induction motor traction drive system. A vehicle performance analysis was performed to establish the vehicle tractive effort-speed requirements. These requirements were then converted into a set of inverter and motor specifications. The inverter was a transistorized three-phase bridge using General Electric power Darlington transistors. The description of the design and development of this inverter is the principal object of this paper. The high-speed induction motor is a design which is optimized for use with an inverter power source. The primary feedback control is a torque angle control with voltage and torque outer loop controls. A current-controlled PWM technique is used to control the motor voltage. The drive has a constant torque output with PWM operation to base motor speed and a constant horsepower output with square wave operation to maximum speed. The drive system was dynamometer tested and the results are presented.

SYNTHESIS OF VOLTAGES OF UNIFORM PWM IN TIME REGULATION

Directory of Open Access Journals (Sweden)

A. G. Stryzhniou

2014-01-01

Full Text Available The article describes a process of synthesis and qualitative assessment of the harmonic composition of voltages of multiple and single PWM pulses in time regulation, being, along with amplitude, frequency and phase method, one of control methods of an asynchronous motor. The main point of time regulation is that a pause after any two single PWM pulses with different polarity or after any two groups of multiple PWM pulses with different polarity changes during a process of regulation. Feature of time regulation is that a motor has fast response in the range of small-signal of control and good linearity of speed-torque characteristics in the whole control range. Analytical expressions of parameters of PWM pulses ai and ti are obtained which allow to simplify considerably a process of formation and implementation of time regulation using tabular or indexed-tabular methods. These expressions allow not only to define voltage amplitude of  harmonic but also to perform qualitative assessment of harmonic composition of output voltages at time regulation. It is specified that harmonic frequencies wi = w0/q change in inverse proportion to magnitude of parameter q during a process of regulation and there is a replacement of a fundamental frequency by frequencies of higher harmonics.The offered approach allows to synthesize voltage of uniform single and multiple PWM pulses and to perform their comparative and qualitative analysis and the obtained expressions can be used at modeling of AC motor work. Voltage of multiple PWM pulses which is formed using stepped reference voltage with even quantity of steps in a half period and a pause on a zero level has the best parameters by criterion of a minimum of harmonic components and a maximum of a factor of anharmonicity Kнс at time regulation.

Mitogenic stimuli and phosphatidylinositol (PI) turnover in cultured 3T3 fibroblasts

International Nuclear Information System (INIS)

Kohler, C.; Petersen, R.

1986-01-01

The hydrolysis of PI and polyphosphoinositides by phopholipase C is an early and rapid response to cell activation by a variety of neurotransmitters, hormones, growth factors and pharmacological agonists. The authors have examined the role of PI turnover and the generation of second messengers (diacylglycerol and inositol trisphosphate) in the mitogenic response of cultured Balb/c and Swiss 3T3 cells to polypeptide growth factors. Cells were prelabelled with 3 H inositol for 18-20 hours, washed and suspended in Herpes + Li + buffer, and stimulated with platelet-derived growth factor (PDGF), vasopressin, insulin, and other growth factors. PI turnover was measured as the increase in total inositol phosphate (IP) production. IP1, IP2, and IP3 were characterized by sequential elution from a Dowex column. Partially purified PDGF produced a 2-4 fold stimulation of total IP production. This was seen as early as 30 seconds after stimulation and increased for up to 1-2 hours. Balb/c cells were more sensitive than Swiss cells to the mitogenic and PI effects of PDGF. Other mitogenic stimuli had differential effects on PI turnover. Vasopressin (4-400 ng/ml) markedly stimulated PI turnover (3-6 fold) in Swiss, but not Balb/c cells. Insulin (100 ng/ml - 10 μg/ml) increased total IP to a greater degree in Balb/c cells. Epidermal growth factor (10 ng/ml - 10 μg/ml) had no effect on PI turnover and fibroblast growth factor (10 ng/ml - 10 μg/ml) only stimulated at the higher concentrations in Swiss cells. Thrombin (1U/ml - 10 U/ml) produced a 1.5 - 2 fold stimulation in Balb/c cells. Thus, various polypeptide growth factors have differential effects on PI turnover depending on their mitogenic potential and the effector cell type

Analysis of Input and Output Ripples of PWM AC Choppers

Directory of Open Access Journals (Sweden)

Pekik Argo Dahono

2008-11-01

Full Text Available This paper presents an analysis of input and output ripples of PWM AC choppers. Expressions of input and output current and voltage ripples of single-phase PWM AC choppers are first derived. The derived expressions are then extended to three-phase PWM AC choppers. As input current and output voltage ripples specification alone cannot be used to determine the unique values of inductance and capacitance of the LC filters, an additional criterion based on the minimum reactive power is proposed. Experimental results are included in this paper to show the validity of the proposed analysis method.

EMC Increasing of PWM Rectifier in Comparison with Classical Rectifier

Directory of Open Access Journals (Sweden)

R. Dolecek

2008-12-01

Full Text Available Pulse width modulated rectifier is a very popular topic nowadays. The modern industrial production demands continuous and lossless conversion of electrical energy parameters. This need leads to wide spread of power semiconductor converters. The rapid development in power electronics and microprocessor technology enables to apply sophisticated control methods that eliminate negative side effects of the power converters on the supply network. The phase controlled thyristor rectifiers overload the supply network with higher harmonics and reactive power consumption. That is why the PWM rectifier is being examined. In comparison with the phase controlled rectifier it can be controlled to consume nearly sinusoidal current with power factor equal to unity. Another advantage is its capability of energy recuperation. The PWM rectifier can assert itself for its good behavior in many applications, for example as an input rectifier in indirect frequency converter, or in traction. Traction vehicles equipped with PWM rectifier do not consume reactive power, do not load the supply network with higher harmonics, and the recuperation is possible. The paper deals with the PWM rectifier functional model realization and examination. Electromagnetic compatibility of PWM rectifier and classical phase controlled rectifier is compared on the basis of the input current harmonic analysis.

A digital input class-D audio amplifier with sixth-order PWM

International Nuclear Information System (INIS)

Luo Shumeng; Li Dongmei

2013-01-01

A digital input class-D audio amplifier with a sixth-order pulse-width modulation (PWM) modulator is presented. This modulator moves the PWM generator into the closed sigma—delta modulator loop. The noise and distortions generated at the PWM generator module are suppressed by the high gain of the forward loop of the sigma—delta modulator. Therefore, at the output of the modulator, a very clean PWM signal is acquired for driving the power stage of the class-D amplifier. A sixth-order modulator is designed to balance the performance and the system clock speed. Fabricated in standard 0.18 μm CMOS technology, this class-D amplifier achieves 110 dB dynamic range, 100 dB signal-to-noise rate, and 0.0056% total harmonic distortion plus noise. (semiconductor integrated circuits)

Parathyroid mitogenic activity in plasma from patients with familial multiple endocrine neoplasia type 1

International Nuclear Information System (INIS)

Brandi, M.L.; Aurbach, G.D.; Fitzpatrick, L.A.; Quarto, R.; Spiegel, A.M.; Bliziotes, M.M.; Norton, J.A.; Doppman, J.L.; Marx, S.J.

1986-01-01

Hyperplasia of the parathyroid glands is a central feature of familial multiple endocrine neoplasia type 1. We used cultured bovine parathyroid cells to test for mitogenic activity in plasma from patients with this disorder. Normal plasma stimulated [ 3 H]thymidine incorporation, on the average, to the same extent as it was stimulated in a plasma-free control culture. This contrasted with the results of the tests with plasma from patients with familial multiple endocrine neoplasia type 1, in which parathyroid mitogenic activity increased 2400 percent over the control value (P less than 0.001). Plasma from these patients also stimulated the proliferation of bovine parathyroid cells in culture, whereas plasma from normal subjects inhibited it. Parathyroid mitogenic activity in plasma from the patients with familial multiple endocrine neoplasia type 1 was greater than that in plasma from patients with various other disorders, including sporadic primary hyperparathyroidism (with adenoma, hyperplasia, or cancer of the parathyroid), sporadic primary hypergastrinemia, sporadic pituitary tumor, familial hypocalciuric hypercalcemia, and multiple endocrine neoplasia type 2 (P less than 0.05). Parathyroid mitogenic activity in the plasma of patients with familial multiple endocrine neoplasia type 1 persisted for up to four years after total parathyroidectomy. The plasma also had far more mitogenic activity in cultures of parathyroid cells than did optimal concentrations of known growth factors or of any parathyroid secretagogue. This mitogenic activity had an apparent molecular weight of 50,000 to 55,000. We conclude that primary hyperparathyroidism in familial multiple endocrine neoplasia type 1 may have a humoral cause

Mitogenic activity of new lectins from seeds of wild Artocarpus species from Vietnam.

Science.gov (United States)

Blasco, E; Ngoc, L D; Aucouturier, P; Preud'Homme, J L; Barra, A

1996-05-01

Proliferative response of human peripheral blood mononuclear cells (PBMC) stimulated by new lectins purified from seeds of differents Artocarpus species from Vietnam (A. asperulus, A. heterophyllus, A. masticata, A. melinoxylus, A. parva and A. petelotii) was studied and compared to those of the lectin jacalin purified from jackfruit (A. heterophyllus) seeds collected in the island La Réunion. All lectins stimulated human PBMC to proliferate, with a variable efficiency of the mitogenic activity. Phenotypic analysis of cells recovered after 7 day-cultures showed that these lectins mostly stimulated CD4+ T lymphocytes. These results suggest that these lectins from different Artocarpus species are similar in terms of their mitogenic activity although their structural features are not identical.

Feedforward Synchronised PWM for Adjustable Speed AC Drives with Different Control Modes

DEFF Research Database (Denmark)

Oleschuk, Valentin; Blaabjerg, Frede; Jensen, Flemming Buus

2002-01-01

This paper presents a novel method of direct synchronised pulswidth modulation (PWM) for three-phase voltage source inverters, feeding induction motors with different control regimes. It is based on the universal algorithm with either simplified algebraic or accurate trigonometric control functions......, with vector approached for determination of the pulse patterns, with vector approach for determination of the pulse patterns. Different control modes of the drive system with synchronised PWM, including standard scalar V/F control, and also V2/F = constant and V/F2 = constant control regimes, have been...... analysed in the paper. Simulations give the behaviour of the PWM techniques proposed. Both continuous and discontinuous schemes of synchronised PWM, applied for the corresponding control regime, have been analysed and compared....

Prediction of power losses in silicon iron sheets under PWM voltage supply

International Nuclear Information System (INIS)

Amar, M.; Kaczmarek, R.; Protat, F.

1994-01-01

The behavior of iron losses in silicon iron steels submitted to a PWM voltage is studied. The influence of modulation parameters (the depth of modulation and the number of eliminated harmonics) is clarified. In particular, the idea of an equivalent alternating pulse voltage that gives the same iron losses as the PWM voltage is established. An estimation formula for iron losses under the PWM voltage is developed based on the loss separation model and the voltage form factor. ((orig.))

Boosted PWM open loop control of hydraulic proportional valves

International Nuclear Information System (INIS)

Amirante, R.; Innone, A.; Catalano, L.A.

2008-01-01

This paper presents an innovative open loop control technique for direct single stage hydraulic proportional valves whose response rate is significantly higher than that obtained by standard open loop control techniques, even comparable to more costly commercial closed loop systems. Different from standard open loop techniques, which provide the coil with a constant current proportional to the target position, the control strategy proposed in this paper employs the peak and hold (P and H) technique, widely used in Diesel engine modern supply systems, to boost the duty cycle value of the pulse width modulation (PWM) signal for a short time, namely during the spool displacement, while maintaining a lower duty cycle for holding the spool in the required opening position. The developed 'boosted PWM' technique only requires a low cost microcontroller, such as a peripheral interface controller (PIC) equipped with a metal oxide semiconductor (MOS) power driver. The PWM parameters are calibrated as a function of the spool displacement so as to maximize the response rate without introducing overshoots: the collected data are stored in the PIC. Different valve opening procedures with step response have been compared to demonstrate the merits of the proposed boosted PWM technique. No overshoots have been registered. Moreover, the proposed method is characterized by a significantly higher response rate with respect to a standard open loop control, which approximately has the same cost. Similar experimental tests show that the proposed boosted PWM technique has a response rate even higher than that provided by the more costly commercial closed loop system mounted on the valve, and it produces no overshoots

Boosted PWM open loop control of hydraulic proportional valves

Energy Technology Data Exchange (ETDEWEB)

Amirante, R.; Catalano, L.A. [Dipartimento di Ingegneria Meccanica e Gestionale, Politecnico di Bari, Via Re David 200, 70125 Bari (Italy); Innone, A. [Universita degli Studi di Foggia, via Napoli, 25 Foggia (Italy)

2008-08-15

This paper presents an innovative open loop control technique for direct single stage hydraulic proportional valves whose response rate is significantly higher than that obtained by standard open loop control techniques, even comparable to more costly commercial closed loop systems. Different from standard open loop techniques, which provide the coil with a constant current proportional to the target position, the control strategy proposed in this paper employs the peak and hold (P and H) technique, widely used in Diesel engine modern supply systems, to boost the duty cycle value of the pulse width modulation (PWM) signal for a short time, namely during the spool displacement, while maintaining a lower duty cycle for holding the spool in the required opening position. The developed 'boosted PWM' technique only requires a low cost microcontroller, such as a peripheral interface controller (PIC) equipped with a metal oxide semiconductor (MOS) power driver. The PWM parameters are calibrated as a function of the spool displacement so as to maximize the response rate without introducing overshoots: the collected data are stored in the PIC. Different valve opening procedures with step response have been compared to demonstrate the merits of the proposed boosted PWM technique. No overshoots have been registered. Moreover, the proposed method is characterized by a significantly higher response rate with respect to a standard open loop control, which approximately has the same cost. Similar experimental tests show that the proposed boosted PWM technique has a response rate even higher than that provided by the more costly commercial closed loop system mounted on the valve, and it produces no overshoots. (author)

High flexibility and low cost digital implementation for modern PWM strategies

DEFF Research Database (Denmark)

Mathe, Laszlo; Sera, Dezso; Kerekes, Tamas

2011-01-01

like AZSPWM, NSPWM, or ACRPWM. By using a conventional PWM unit from a microcontroller, these modern modulation techniques are often difficult, or even impossible, to implement. The proposed method can be used to implement PWM strategies even for those microcontrollers which are not equipped...

Glucose, other secretagogues, and nerve growth factor stimulate mitogen-activated protein kinase in the insulin-secreting beta-cell line, INS-1

DEFF Research Database (Denmark)

Frödin, M; Sekine, N; Roche, E

1995-01-01

The signaling pathways whereby glucose and hormonal secretagogues regulate insulin-secretory function, gene transcription, and proliferation of pancreatic beta-cells are not well defined. We show that in the glucose-responsive beta-cell line INS-1, major secretagogue-stimulated signaling pathways...... converge to activate 44-kDa mitogen-activated protein (MAP) kinase. Thus, glucose-induced insulin secretion was found to be associated with a small stimulatory effect on 44-kDa MAP kinase, which was synergistically enhanced by increased levels of intracellular cAMP and by the hormonal secretagogues......-1. Phorbol ester, an activator of protein kinase C, stimulated 44-kDa MAP kinase by both Ca(2+)-dependent and -independent pathways. Nerve growth factor, independently of changes in cytosolic Ca2+, efficiently stimulated 44-kDa MAP kinase without causing insulin release, indicating that activation...

Induced overexpression of protein kinase D1 stimulates mitogenic signaling in human pancreatic carcinoma PANC-1 cells.

Science.gov (United States)

Kisfalvi, Krisztina; Hurd, Cliff; Guha, Sushovan; Rozengurt, Enrique

2010-05-01

Neurotensin (NT) stimulates protein kinase D1 (PKD1), extracellular signal regulated kinase (ERK), c-Jun N-terminal Kinase (JNK), and DNA synthesis in the human pancreatic adenocarcinoma cell line PANC-1. To determine the effect of PKD1 overexpression on these biological responses, we generated inducible stable PANC-1 clones that express wild-type (WT) or kinase-dead (K618N) forms of PKD1 in response to the ecdysone analog ponasterone-A (PonA). NT potently stimulated c-Jun Ser(63) phosphorylation in both wild type and clonal derivatives of PANC-1 cells. PonA-induced expression of WT, but not K618N PKD1, rapidly blocked NT-mediated c-Jun Ser(63) phosphorylation either at the level of or upstream of MKK4, a dual-specificity kinase that leads to JNK activation. This is the first demonstration that PKD1 suppresses NT-induced JNK/cJun activation in PANC-1 cells. In contrast, PKD1 overexpression markedly increased the duration of NT-induced ERK activation in these cells. The reciprocal influence of PKD1 signaling on pro-mitogenicERK and pro-apopotic JNK/c-Jun pathways prompted us to examine whether PKD1 overexpression promotes DNA synthesis and proliferation of PANC-1 cells. Our results show that PKD1 overexpression increased DNA synthesis and cell numbers of PANC-1 cells cultured in regular dishes or in polyhydroxyethylmethacrylate [Poly-(HEMA)]-coated dishes to eliminate cell adhesion (anchorage-independent growth). Furthermore, PKD1 overexpression markedly enhanced DNA synthesis induced by NT (1-10 nM). These results indicate that PKD1 mediates mitogenic signaling in PANC-1 and suggests that this enzyme could be a novel target for the development of therapeutic drugs that restrict the proliferation of these cells.

A PWM strategy for acoustic noise reduction for grid-connected single-phase inverters

Energy Technology Data Exchange (ETDEWEB)

Shao, R.; Guo, Z.; Chang, L. [New Brunswick Univ., Fredericton, NB (Canada). Dept. of Electrical and Computer Engineering

2006-07-01

This paper presented a newly proposed and improved pulse width modulation (PWM) strategy for grid-connected single-phase inverters. Small distributed generators using energy from renewable resources such as PV and wind systems typically use grid-connected single-phase inverters as voltage source inverters for good acoustic performance. PWM is generally applied in these inverters in order to achieve good waveforms of output current as required by interconnection standards. In routine simultaneous switching PWM methods, the current ripples through the inverter output filter inductor are at the carrier switching frequency, which is one of the major causes for inverter acoustic noise. The new PWM strategy effectively alleviates acoustic noise and improves output power quality. It is based on the principle of evenly splitting the switching of Insulated Gate Bipolar Transistors (IGBT) in each switching cycle among all IGBTs of the full bridge, thereby using a non-simultaneous mode of PWM which doubles the output current ripple frequency. This increases the inductor current ripple frequency to twice the carrier frequency. It is therefore possible to increase the current ripple frequency, or noise frequency into the range of ultrasonic which is inaudible to the human ear, without increasing the inverter's switching frequency to which the inverter's switching loss is proportional. In addition, this new PWM scheme can reduce the output current harmonics distortion and dc link current ripples. As such, lower capacitance in dc link capacitors and lower inductance of output inductor are needed. The improved PWM scheme was verified in a 3 kW grid-connected single-phase inverter. It was shown that the PWM strategy can be readily implemented with a digital signal processing microcontroller. 8 refs., 11 figs.

Mitogen activated protein kinases selectively regulate palytoxin-stimulated gene expression in mouse keratinocytes

International Nuclear Information System (INIS)

Zeliadt, Nicholette A.; Warmka, Janel K.; Wattenberg, Elizabeth V.

2003-01-01

We have been investigating how the novel skin tumor promoter palytoxin transmits signals through mitogen activated protein kinases (MAPKs). Palytoxin activates three major MAPKs, extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38, in a keratinocyte cell line derived from initiated mouse skin (308). We previously showed that palytoxin requires ERK to increase matrix metalloproteinase-13 (MMP-13) gene expression, an enzyme implicated in carcinogenesis. Diverse stimuli require JNK and p38 to increase MMP-13 gene expression, however. We therefore used the JNK and p38 inhibitors SP 600125 and SB 202190, respectively, to investigate the role of these MAPKs in palytoxin-induced MMP-13 gene expression. Surprisingly, palytoxin does not require JNK and p38 to increase MMP-13 gene expression. Accordingly, ERK activation, independent of palytoxin and in the absence of JNK and p38 activation, is sufficient to induce MMP-13 gene expression in 308 keratinocytes. Dexamethasone, a synthetic glucocorticoid that inhibits activator protein-1 (AP-1), blocked palytoxin-stimulated MMP-13 gene expression. Therefore, the AP-1 site present in the promoter of the MMP-13 gene appears to be functional and to play a key role in palytoxin-stimulated gene expression. Previous studies showed that palytoxin simulates an ERK-dependent selective increase in the c-Fos content of AP-1 complexes that bind to the promoter of the MMP-13 gene. JNK and p38 can also modulate c-Fos. Palytoxin does not require JNK or p38 to increase c-Fos binding, however. Altogether, these studies indicate that ERK plays a distinctly essential role in transmitting palytoxin-stimulated signals to specific nuclear targets in keratinocytes derived from initiated mouse skin

Optimal conditions in (/sup 3/H)-thymidine uptake studies to prevent radiation damage to cells. A scintimetric and cytofluorographic analysis

Energy Technology Data Exchange (ETDEWEB)

Ruiz-Arguelles, A; Llorente, L; Diaz-Jouanen, E; Alarcon-Segovia, D [Instituto Nacional de la Nutricion, Mexico City

1981-12-01

Cells subjected to nucleoside incorporation studies using radiolabelled materials may suffer radiation damage that can alter the results. Scintimetric and cytofluorographic analyses were performed to confirm this and to determine the optimal experimental doses of, and exposure times to, (/sup 3/H)-TdR, in order to prevent or minimize such radiation damage to cells. The results showed that cultures of human mononuclear cells should be pulsed with 0.125 ..mu..Ci for 14 hr when stimulated with phytohaemagglutinin, 0.125 ..mu..Ci for 18 hr when stimulated with pokeweed mitogen, 0.5 ..mu..Ci for 8 hr when stimulated with concanavalin A and 0.5 ..mu..Ci for 8 hr when subjected to allogeneic stimulus, in order to achieve optimal incorporation with minimal disturbances of the cell cycle.

T-dependence of human B lymphocyte proliferative response to mitogens.

Science.gov (United States)

Brochier, J; Samarut, C; Gueho, J P; Revillard, J P

1976-01-01

Human peripheral blood and tonsil lymphocytes were fractionated on anti-Ig-coated Sephadex columns or by centrifugation after rosetting with native sheep erythrocytes. Both methods allowed the recovery of B and T-enriched populations the purity of which was checked by fluorescein-labelled anti-Ig serum, E and EAC rosette formation, and heterologous antisera specific for B or T lymphocytes. The proliferative response of T cells to PHA, Con A, PWM, and ALS was not found different from that of unfractionated cells, whereas no response of the B cells could be observed to these mitogens providing that no contaminating T cells were present. Addition of T lymphocytes to these unresponsive B cells allowed them to respond to phytomitogens, but not to ALS. X-irradiated T cells could, to some extent, replace the diving T lymphocytes; no T-replacing factor could be found in cell-free supernatants from T cells, whether or not they had been activated by mitrogens. This model of B-T cooperation appears useful for studying the differentiation and maturation of human B lymphocytes.

A dual-path, current-sensing resistor-free boost LED driver with fast PWM dimming

International Nuclear Information System (INIS)

Zhou Minchao; Lü Danzhu; Cheng Lin; Hong Zhiliang; Liu, Bill Yang

2013-01-01

A boost LED driver featuring a high PWM dimming ratio and optimized efficiency is presented. This LED driver, which has a low dropout voltage and is able to drive 3–7 LEDs in series with constant output current and fast PWM dimming, provides an alternative technique for brightness adjustment. A dual-path control scheme with automatic switching and state maintenance is proposed. Meanwhile, a cascode current mirror structure is applied with the output transistor multiplexed as an LED PWM dimming transistor. Implemented in 0.5 μm 25 V BCD process, the measurement results show that a voltage conversion range of 5 V input to 6–24 V output with constant output current is obtained. With automatically switching dual-path control and an optimized current mirror, the response time during PWM dimming is reduced to as low as 240 ns and the efficiency keeps above 89% over a wide PWM dimming ratio - 250 mA output current. (semiconductor integrated circuits)

Discrete/PWM Ballast-Resistor Controller

Science.gov (United States)

King, Roger J.

1994-01-01

Circuit offers low switching loss and automatic compensation for failure of ballast resistor. Discrete/PWM ballast-resistor controller improved shunt voltage-regulator circuit designed to supply power from high-resistance source to low-impedance bus. Provides both coarse discrete voltage levels (by switching of ballast resistors) and continuous fine control of voltage via pulse-width modulation.

Precipitin response of the mitogen produced by Strongylus vulgaris arterial larvae.

Science.gov (United States)

Adeyefa, C A

1992-07-01

The precipitin response of the mitogen produced by Strongylus vulgaris arterial larvae was investigated. IgG (T) from the sera of horses naturally infected with S. vulgaris adults and arterial larvae recognised the presence of two antigenic components of the mitogenic fractions. The results obtained seem to confirm that these antigens are immunogenic in stimulating the production of increased levels of IgG(T) in infected animals, and showed that the procedures could be used as immunological tools in the diagnosis of S. vulgaris infection.

Improved detection rate of cytogenetic abnormalities in chronic lymphocytic leukemia and other mature B-cell neoplasms with use of CpG-oligonucleotide DSP30 and interleukin 2 stimulation.

Science.gov (United States)

Shi, Min; Cipollini, Matthew J; Crowley-Bish, Patricia A; Higgins, Anne W; Yu, Hongbo; Miron, Patricia M

2013-05-01

Detection of cytogenetic abnormalities requires successful culture of the clonal population to obtain metaphase chromosomes for study, and as such, has been hampered by low mitotic indices of mature B cells in culture. Our study presents data on the improved abnormality detection rate with the use of a CpG-oligonucleotide/interleukin 2 (OL/IL-2) culture protocol for mature B-cell neoplasms, including chronic lymphocytic leukemia (CLL) and non-CLL specimens. The increased detection rate of abnormalities, compared with unstimulated culture and traditional pokeweed mitogen culture, was statistically significant for both CLL and non-CLL neoplasms. For CLL specimens, our data also showed that for cytogenetically visible aberrations, OL/IL-2 was as, if not more, sensitive than detection with interphase fluorescence in situ hybridization (iFISH). Use of OL/IL-2 allowed a number of abnormalities to be detected, which were not covered by specific iFISH panels, especially balanced translocations. Therefore, OL/IL-2 stimulation improves diagnostic sensitivity and increases discovery rate of novel prognostic findings.

Electrical stimulation with periodic alternating intervals stimulates neuronal cells to produce neurotrophins and cytokines through activation of mitogen-activated protein kinase pathways.

Science.gov (United States)

Yamamoto, Kenta; Yamamoto, Toshiro; Honjo, Kenichi; Ichioka, Hiroaki; Oseko, Fumishige; Kishida, Tsunao; Mazda, Osam; Kanamura, Narisato

2015-12-01

Peripheral neuropathy is a representative complication of dental surgery. Electrical therapy, based on electrical stimulation with periodic alternating intervals (ES-PAI), may promote nerve regeneration after peripheral nerve injury in a non-invasive manner, potentially providing an effective therapy for neuropathy. This study aimed to analyze the molecular mechanisms underlying the nerve recovery stimulated by ES-PAI. In brief, ES-PAI was applied to a neuronal cell line, Neuro2A, at various intensities using the pulse generator apparatus, FREUDE. Cell viability, neurotrophin mRNA expression, and cytokine production were examined using a tetrazolium-based assay, real-time RT-PCR, and ELISA, respectively. Mitogen-activated protein kinase (MAPK) signaling was assessed using flow cytometry. It was found that ES-PAI increased the viability of cells and elevated expression of nerve growth factor (NGF) and neurotrophin-3 (NT-3); ESPAI also augmented vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) expression, which was restored by addition of p38 inhibitors. Phosphorylation of p38 and extracellular signal-regulated kinase 1/2 (ERK-1/2) was augmented by ES-PAI. Hence, ES-PAI may ameliorate peripheral neuropathy by promoting neuronal cell proliferation and production of neurogenic factors by activating p38 and ERK-1/2 pathways. © 2015 Eur J Oral Sci.

Expression profiles of the immune genes CD4, CD8β, IFNγ, IL-4, IL-6 and IL-10 in mitogen-stimulated koala lymphocytes (Phascolarctos cinereus by qRT-PCR

Directory of Open Access Journals (Sweden)

Iona E. Maher

2014-03-01

Full Text Available Investigation of the immune response of the koala (Phascolarctos cinereus is needed urgently, but has been limited by scarcity of species-specific reagents and methods for this unique and divergent marsupial. Infectious disease is an important threat to wild populations of koalas; the most widespread and important of these is Chlamydial disease, caused by Chlamydia pecorum and Chlamydia pneumoniae. In addition, koala retrovirus (KoRV, which is of 100% prevalence in northern Australia, has been proposed as an important agent of immune suppression that could explain the koala’s susceptibility to disease. The correct balance of T regulatory, T helper 1 (Th1 and Th2 lymphocyte responses are important to an individual’s susceptibility or resistance to chlamydial infection. The ability to study chlamydial or KoRV pathogenesis, effects of environmental stressors on immunity, and the response of koalas to vaccines under development, by examining the koala’s adaptive response to natural infection or in-vitro stimulation, has been limited to date by a paucity of species- specific reagents. In this study we have used cytokine sequences from four marsupial genomes to identify mRNA sequences for key T regulatory, Th1 and Th2 cytokines interleukin 4 (IL-4, interleukin 6 (IL-6, interleukin 10 (IL-10 and interferon gamma (IFNγ along with CD4 and CD8β. The koala sequences used for primer design showed >58% homology with grey short-tailed opossum, >71% with tammar wallaby and 78% with Tasmanian devil amino acid sequences. We report the development of real-time RT-PCR assays to measure the expression of these genes in unstimulated cells and after three common mitogen stimulation protocols (phorbol myristate acetate/ionomycin, phorbol myristate acetate/phytohemagglutinin and concanavalin A. Phorbol myristate acetate/ionomycin was found to be the most effective mitogen to up-regulate the production of IL-4, IL-10 and IFNγ. IL-6 production was not

Expression profiles of the immune genes CD4, CD8β, IFNγ, IL-4, IL-6 and IL-10 in mitogen-stimulated koala lymphocytes (Phascolarctos cinereus) by qRT-PCR.

Science.gov (United States)

Maher, Iona E; Griffith, Joanna E; Lau, Quintin; Reeves, Thomas; Higgins, Damien P

2014-01-01

Investigation of the immune response of the koala (Phascolarctos cinereus) is needed urgently, but has been limited by scarcity of species-specific reagents and methods for this unique and divergent marsupial. Infectious disease is an important threat to wild populations of koalas; the most widespread and important of these is Chlamydial disease, caused by Chlamydia pecorum and Chlamydia pneumoniae. In addition, koala retrovirus (KoRV), which is of 100% prevalence in northern Australia, has been proposed as an important agent of immune suppression that could explain the koala's susceptibility to disease. The correct balance of T regulatory, T helper 1 (Th1) and Th2 lymphocyte responses are important to an individual's susceptibility or resistance to chlamydial infection. The ability to study chlamydial or KoRV pathogenesis, effects of environmental stressors on immunity, and the response of koalas to vaccines under development, by examining the koala's adaptive response to natural infection or in-vitro stimulation, has been limited to date by a paucity of species- specific reagents. In this study we have used cytokine sequences from four marsupial genomes to identify mRNA sequences for key T regulatory, Th1 and Th2 cytokines interleukin 4 (IL-4), interleukin 6 (IL-6), interleukin 10 (IL-10) and interferon gamma (IFNγ) along with CD4 and CD8β. The koala sequences used for primer design showed >58% homology with grey short-tailed opossum, >71% with tammar wallaby and 78% with Tasmanian devil amino acid sequences. We report the development of real-time RT-PCR assays to measure the expression of these genes in unstimulated cells and after three common mitogen stimulation protocols (phorbol myristate acetate/ionomycin, phorbol myristate acetate/phytohemagglutinin and concanavalin A). Phorbol myristate acetate/ionomycin was found to be the most effective mitogen to up-regulate the production of IL-4, IL-10 and IFNγ. IL-6 production was not consistently up-regulated by

Role of Akt/PKB and PFKFB isoenzymes in the control of glycolysis, cell proliferation and protein synthesis in mitogen-stimulated thymocytes.

Science.gov (United States)

Houddane, Amina; Bultot, Laurent; Novellasdemunt, Laura; Johanns, Manuel; Gueuning, Marie-Agnès; Vertommen, Didier; Coulie, Pierre G; Bartrons, Ramon; Hue, Louis; Rider, Mark H

2017-06-01

Proliferating cells depend on glycolysis mainly to supply precursors for macromolecular synthesis. Fructose 2,6-bisphosphate (Fru-2,6-P 2 ) is the most potent positive allosteric effector of 6-phosphofructo-1-kinase (PFK-1), and hence of glycolysis. Mitogen stimulation of rat thymocytes with concanavalin A (ConA) led to time-dependent increases in lactate accumulation (6-fold), Fru-2,6-P 2 content (4-fold), 6-phosphofructo-2-kinase (PFK-2)/fructose-2,6-bisphosphatase isoenzyme 3 and 4 (PFKFB3 and PFKFB4) protein levels (~2-fold and ~15-fold, respectively) and rates of cell proliferation (~40-fold) and protein synthesis (10-fold) after 68h of incubation compared with resting cells. After 54h of ConA stimulation, PFKFB3 mRNA levels were 45-fold higher than those of PFKFB4 mRNA. Although PFKFB3 could be phosphorylated at Ser461 by protein kinase B (PKB) in vitro leading to PFK-2 activation, PFKFB3 Ser461 phosphorylation was barely detectable in resting cells and only increased slightly in ConA-stimulated cells. On the other hand, PFKFB3 and PFKFB4 mRNA levels were decreased (90% and 70%, respectively) by exposure of ConA-stimulated cells to low doses of PKB inhibitor (MK-2206), suggesting control of expression of the two PFKFB isoenzymes by PKB. Incubation of thymocytes with ConA resulted in increased expression and phosphorylation of the translation factors eukaryotic initiation factor-4E-binding protein-1 (4E-BP1) and ribosomal protein S6 (rpS6). Treatment of ConA-stimulated thymocytes with PFK-2 inhibitor (3PO) or MK-2206 led to significant decreases in Fru-2,6-P 2 content, medium lactate accumulation and rates of cell proliferation and protein synthesis. These data were confirmed by using siRNA knockdown of PFKFB3, PFKFB4 and PKB α/β in the more easily transfectable Jurkat E6-1 cell line. The findings suggest that increased PFKFB3 and PFKFB4 expression, but not increased PFKFB3 Ser461 phosphorylation, plays a role in increasing glycolysis in mitogen-stimulated

Performance analysis of samarium cobalt P.M. synchronous motor fed from PWM inverters

International Nuclear Information System (INIS)

Rahman, M.A.; Choudhury, M.A.

1985-01-01

This paper presents an analysis and performance of samarium cobalt permanent magnet (P.M.) synchronous motors fed from two types of voltage source pulse width modulated (PWM) inverters. The analysis and test results on the steady state performance of a P.M. motor fed from PWM inverters are presented. PWM inverters are used in variable voltage variable frequency applications to avoid a double conversion process of ordinary inverters. In drives, they are used for voltage and speed regulation of motors. Use of modulation technique in inverters also allow to eliminate or minimize selected harmonics from the inverter output voltage

Neural network based PWM AC chopper fed induction motor drive

Directory of Open Access Journals (Sweden)

Venkatesan Jamuna

2009-01-01

Full Text Available In this paper, a new Simulink model for a neural network controlled PWM AC chopper fed single phase induction motor is proposed. Closed loop speed control is achieved using a neural network controller. To maintain a constant fluid flow with a variation in pressure head, drives like fan and pump are operated with closed loop speed control. The need to improve the quality and reliability of the drive circuit has increased because of the growing demand for improving the performance of motor drives. With the increased availability of MOSFET's and IGBT's, PWM converters can be used efficiently in low and medium power applications. From the simulation studies, it is seen that the PWM AC chopper has a better harmonic spectrum and lesser copper loss than the Phase controlled AC chopper. It is observed that the drive system with the proposed model produces better dynamic performance, reduced overshoot and fast transient response. .

B cells in the appendix and other lymphoid organs of the rabbit: stimulation of DNA synthesis by anti-immunoglobulin

International Nuclear Information System (INIS)

Calkins, C.E.; Ozer, H.; Waksman, B.H.

1975-01-01

Lymphocytes from rabbit lymphoid organs were cultured in the presence of class specific anti-immunoglobulin sera and of anti-allotype sera. Stimulation of tritiated thymidine uptake into DNA was taken to indicate the presence of the corresponding immunoglobulins on the cell surfaces. Thymus and bone marrow lymphocytes were unresponsive to all reagents tested. Popliteal lymph node contained cells responsive to anti-μ, anti-γ, and anti-α and therefore presumably bearing IgM, IgG, and IgA. Spleen had only IgM- and IgG-bearing cells, and the appendix contained cells with IgM and IgA receptors only. The lymph node, spleen, and appendix cells of rabbits depleted of B lymphocytes by irradiation (900 R) and injection of thymocytes were unresponsive to anti-immunoglobulin but were stimulated at almost normal levels by PHA and Con A. T cell-depleted animals (thymectomy, irradiation with three divided doses of 450 R and bone marrow shielding) had immunoglobulin-bearing lymphocytes but were unresponsive to the mitogens. However a moderate level of mitogen-responsiveness reappeared by 3 to 4 wk after irradiation. Cells of morphologically distinct regions of the appendix, separated manually, showed different responses corresponding to the inferred origins of these anatomic areas. The ''dome'' and ''corona'' contained functional IgM- and IgA-bearing cells. The ''TDA'' reacted well to PHA, Con A, and PWM, but was depleted of immunoglobulin-bearing cells. The ''follicle'' cells, which are almost all in active DNA synthesis or mitosis, were relatively unresponsive to either T or B cell stimuli. Anti-allotype serum stimulated the same populations which responded to class-specific heteroantisera but at a slightly lower level. It was inferred that gut-associated lymphoid tissues like the appendix may play a special role as an amplification site for B-cells destined to produce IgM and IgA elsewhere in the organism

Apparent permeability of electrical steel under PWM magnetisation

International Nuclear Information System (INIS)

Moses, A.J.; Leicht, J.; Anderson, P.

2006-01-01

In recent years much attention has been paid to material performance under pulse width modulation (PWM) excitation conditions, which is of increasing importance to motor applications particularly in energy efficient variable speed drive systems. It is well known that in general, losses increase significantly with reducing modulation index, the increase depending on parameters such as silicon contents, thickness and grain size. The effect of the PWM waveform on permeability has attracted little attention until now. So in this paper its influence on the permeability of electrical steel is analysed and characterised. A prediction approach based on the permeability under sine wave excitation and total harmonic distortion is introduced which results in errors below 10% for non-electrical steel at 1.5 T

PWM pulse pattern optimization method using carrier frequency modulation. Carrier shuhasu hencho ni yoru PWM pulse pattern saitekikaho

Energy Technology Data Exchange (ETDEWEB)

Iwaji, Y.; Fukuda, S. (Hokkaido University, Sapporo (Japan))

1991-07-15

Sinusoidal inverters are getting more widely used keeping pace with the development of semiconductor switching elements. This paper discusses optimizing a PWM pulse pattern at an inverter output to drive an induction motor, proposes methods for improving distortion and torque ripples using a carrier frequency modulation (CFM), and describes a method for realizing the improvement through use of a single-chip microcomputer. The method defines evaluation parameters corresponding to the distortion and torque ripples, and optimizes the CFM depth to the parameters. The PWM pulse pattern has its voltage vector and time width so selected that the time integrated space vector of a three-phase voltage approaches a circular locus. Furthermore, the carrier frequency, that is the sampling frequency of the inverter, is also adjusted so that the above evaluation parameters are minimized. The addition of a new variable called the frequency modulation provides freedom in selecting an output characteristic as called for by the purpose. 12 refs., 18 figs.

A new power supply regulated PWM-ZCS supplied in current: analysis, project and experiments; Uma nova fonte chaveada PWM-ZCS alimentada em corrente: analise, projeto e experimentacao

Energy Technology Data Exchange (ETDEWEB)

Barbosa, Peter Mantovanelli

1993-10-01

This work introduces a new power supply by PWM, operating at constant frequency, with soft communication. The new topology uses only two active switches and absorbs the transformer leakage inductance. Besides, the soft communication takes place with no conduction loss penalty, in comparison with conventional hard switch PWM converters. Principle of operation, analysis, design and experimentation results taken from laboratory prototype rated at 400 W/48 v, 40 Khz, using IGBT are presented. (author) 10 refs., 71 figs.

PWM control of current source type six-phase inverter with improved waveforms by coupling reactor; Ketsugo reactor ni yori hakei kaizen sareta denryugata rokuso inverter no PWM seigyo

Energy Technology Data Exchange (ETDEWEB)

Inami, K.; Danjo, M.; Kondo, Y.; Yamada, M. [Niihama Technical College, Ehime (Japan); Toki, K. [Shikoku Electric Power Co., Inc., Kagawa (Japan); Heike, J. [Shikoku Instrumentation Co. Ltd., Kagawa (Japan)

1998-10-01

A PWM method has been applied to a high capacity six phase current source inverter system in order to obtain sinusoidal output voltage and current. In this system, the three-phase coupling reactor is connected between the inverter output and an induction motor used as a load. Then the reactor eliminates harmonic components included in the inverter output current except 12k {+-} 1 (k=1,2,3)th order. As a result, the distortion factor of the inverter output current decreases. But the resonant circuit is composed of the capacitance of filter capacitor and the induction motor leakage inductance. Then the resonance current is superimposed on the induction motor phase currents. To solve this problem, the optimal PWM pattern is derived, so that the resonant current becomes very small. The order of the resonant frequency component of the induction motor phase current depend on the inverter frequency. Then total inverter frequency range is divided into several areas. The optimal PWM pattern is derived in each areas. As a result, the use of each optimal PWM pattern allows us to drive the induction motor, over a wide range of speed, under the condition of small distortion factor of phase currents. 5 refs., 10 figs., 1 tab.

EVALUATION OF VARIOUS UNIPOLAR MULTICARRIER PWM STRATEGIES FOR FIVE LEVEL FLYING CAPACITOR INVERTER

Directory of Open Access Journals (Sweden)

B. SHANTHI

2012-06-01

Full Text Available This paper presents the comparison of unipolar multicarrier Pulse Width Modulation (PWM techniques for the Flying Capacitor Multi Level Inverter (FCMLI. Due to switch combination redundancies, there are certain degrees of freedom to generate the five level AC output voltage. This paper presents the use of Control Freedom Degree (CFD combination. The effectiveness of the PWM strategies developed using CFD are demonstrated by simulation and experimentation. The results indicate that the multilevel inverter triggered by the developed USHPWM strategy exhibits reduced harmonics. PWM strategies developed are implemented in real time using dSPACE/Real Time Interface (RTI. The simulation and experimental output closely match with each other validating the strategies presented.

Restoration of lymphocyte proliferation and CTL generation by murine rIL-2 after treatment of allogeneic stimulator cells by ultraviolet B irradiation, heat, or paraformaldehyde

International Nuclear Information System (INIS)

Flye, M.W.; Yu, S.

1991-01-01

Following a 5-day mixed lymphocyte culture (MLC), C3H/HeJ (H-2k) splenocytes stimulated with DBA/2 (H-2d) gamma-irradiated splenocytes (2000 rads) are specifically cytotoxic in a 4-hr 51 Cr-release assay to P815 (H-2d) target cells (62 +/- 2% cytolysis) but not to third-party EL4 (H-2b). However, when the DBA/2 stimulator cells were treated with heat inactivation (45 degree C for 1 hr), fixed with 1% paraformaldehyde (15 min), or irradiated with ultraviolet-B light (10(4) J/M2), no cell proliferation or cytolytic activity developed in the MLCs. The levels of IL-1, IL-2, and IL-6 from the supernatants of MLC using stimulators undergoing either of the three treatments were markedly decreased compared with that from gamma-irradiated stimulators. Both cell proliferation and specific cytolysis were restored in a dose-dependent fashion by the addition of murine rIL-2 to the MLCs. If the stimulator cells were first activated with 5 micrograms/ml pokeweed mitogen or lipopolysaccharide for 2 days, the subsequent treatment with heat, paraformaldehyde, or UV-B did not significantly affect the development of cytolysis (54-70% cytolysis). Suppressor cells were not detected when cells from the nonresponsive MLCs (2.5 x 10(6) cells) were added to an MLC freshly prepared with gamma-irradiated stimulator cells, or were injected intraperitoneally (50 x 10(6) cells) into naive mice 2 days before recovery and in vitro sensitization of splenocytes. Therefore, modification of the stimulating alloantigen can prevent the release of cytokines that function as an essential second signal in the development of the proliferative response and subsequent cytolysis. The cytokine found to be essential for restoration of this response is IL-2

Soft Switching Full-Bridge PWM DC/DC Converter Using Secondary Snubber

Directory of Open Access Journals (Sweden)

Jaroslav Dudrik

2009-05-01

Full Text Available A novel full-bridge PWM DC/DCconverter with controlled secondary side rectifier usingsecondary snubber is presented in this paper.Limitation of the circulating current as well as softswitching for all power switches of the inverter isachieved for full load range from no-load to shortcircuit by using controlled rectifier and snubber on thesecondary side. Phase shift PWM control strategy isused for the converter. The principle of operation isexplained and analyzed and the experimental resultson a 1kW, 50 kHz laboratory model of the converterare presented.

Led spectral and power characteristics under hybrid PWM/AM dimming strategy

DEFF Research Database (Denmark)

Beczkowski, Szymon; Munk-Nielsen, Stig

2010-01-01

In order to dim LEDs the pulse width modulation (PWM) or amplitude modulation (AM) dimming scheme is typically used. Previous studies show that these dimming schemes can have opposite effects on diodes peak wavelength shift. An experimental study was conducted to test the behavior of InGaN diodes...... and phosphor-converted white diodes under hybrid PWM/AM modulation. Feed forward control schemes that provide stable peak wavelength position during dimming and the ability to compensate the thermally induced color shifts and the decrease of the luminous flux are investigated....

Highly Sensitive and Wide-Dynamic-Range Multichannel Optical-Fiber pH Sensor Based on PWM Technique

OpenAIRE

Md. Rajibur Rahaman Khan; Shin-Won Kang

2016-01-01

In this study, we propose a highly sensitive multichannel pH sensor that is based on an optical-fiber pulse width modulation (PWM) technique. According to the optical-fiber PWM method, the received sensing signal?s pulse width changes when the optical-fiber pH sensing-element of the array comes into contact with pH buffer solutions. The proposed optical-fiber PWM pH-sensing system offers a linear sensing response over a wide range of pH values from 2 to 12, with a high pH-sensing ability. The...

In vivo and in vitro radiation effects on canine lymphocyte blastogenesis patterns

International Nuclear Information System (INIS)

Gruber, D.F.; Monroy, R.L.; MacVittlie, T.J.

1984-01-01

Circulating mononuclear cell populations mobilized by dextran sulfate were selected by continuous-flow centrifugation leukapheresis (CFCL) and counterflow centrifugation-elutriation (CCE). Mitogenic (PHA, CON-A, LPS, PWM) response patterns of mononuclear cells were examined after in vitro cobalt-60 irradiation. Radiation doses totaling 10-1000 cGy were given at a rate of 40 cGy/minute. 10/sup 6/ mononuclear cells were added to RPMI-1640 supplemented with 5% heat-inactivated fetal calf serum and an optimum level of mitogen. Uptake of /sup 3/H-TdR was examined after 2, 24, and 48 hrs of culture. All cultures received 1 μCi 3H-TdR for 18 hrs before harvesting. With 2 hr incubation and overall radiation doses examined (10-1000 cGy) only background levels were decreased: PHA, CON-A, and LPS levels were increased by 4-25%, and PWM was substantially increased 120% above normal. With 24 hrs of culture, almost all radiation levels examined showed significantly decreased thymidine uptake. Cells responsive to PHA stimulation showed the greatest sensitivity to radiation, decreasing /sup 3/H-TdR uptake almost 60% when irradiated with the minimal 10-cGy dose. Cells responsive to LPS did not show radiation effects until irradiated with more than 100 cGy. Cells responsive to PWM showed the greatest degree of radio-resistance, and did not significantly decrease until irradiated with levels of 250 cGy or more

Isolated PDM and PWM DC-AC SICAMs[Pulse Density Modulated; Pulse Width Modulated

Energy Technology Data Exchange (ETDEWEB)

Ljusev, P.

2004-03-15

In this report a class of isolated PDM and PWM DC-AC SICAMs is described, which introduce the audio reference only in the output stage. AC-DC power supply is implemented in its simplest form: diode rectifier followed by a medium-size charge-storage capacitor. Isolation from the AC mains is achieved using a high frequency (HF) transformer, receiving the HF voltage pulses from the input 'inverter' stage and transferring them to the output 'rectifier+inverter' stage, which can use either PDM or PWM. The latter stage is then interfaced to the load using an output low-pass filter. Each of the dedicated stages is discussed in detail. Measurements on the master/slave PWM DC-AC SICAM prototype are presented to help benchmarking the performance of this class of SICAMs and identify the advantages and drawbacks. (au)

The 120V 20A PWM switch for applications in high power distribution

Science.gov (United States)

Borelli, V.; Nimal, W.

1989-08-01

A 20A/120VDC (voltage direct current) PWM (Pulse Width Modulation) Solid State Power Controller (SSPC) developed under ESA contract to be used in the power distribution system of Columbus is described. The general characteristics are discussed and the project specification defined. The benefits of a PWM solution over a more conventional approach, for the specific application considered are presented. An introduction to the SSPC characteristics and a functional description are presented.

High frequency three-phase PWM grid connected drive using silicon-carbide switches

DEFF Research Database (Denmark)

Kouchaki, Alireza; Pedersen, Jacob Lykke; Nymand, Morten

2016-01-01

This paper presents controller design procedure for a fully silicon-carbide (SiC) based three-phase grid-connected PWM drive. The influence of the feedforward compensation for the presented setup is studied and the transfer function of the system with feedforward is derived and compared with the ......This paper presents controller design procedure for a fully silicon-carbide (SiC) based three-phase grid-connected PWM drive. The influence of the feedforward compensation for the presented setup is studied and the transfer function of the system with feedforward is derived and compared...

Polyclonal activation of rat B cells. I. A single mitogenic signal can stimulate proliferation, but three signals are required for differentiation

International Nuclear Information System (INIS)

Stunz, L.L.; Feldbush, T.L.

1986-01-01

A water-soluble, proteinaceous preparation derived from the cell walls of Salmonella typhimurium Re mutants has recently been tested in this laboratory for its ability to act as a mitogen for rat lymphocytes. This preparation (STM) has been found to be a potent simulator of B lymphocyte proliferation, as measured both by 3 H-TdR incorporation and by cell cycle analysis performed with flow cytofluorometry. STM stimulates approximately 50% of rat B cells to enter cycle. Previous investigations by others have shown that at least two sets of signals are required for B cell differentiation; (a) proliferation signals that may consist of both a stimulator of B cell conversion from G 0 to G 1 and growth factors, and (b) differentiation signals that probably include at least two B cell differentiation factors (BCDF). When STM was tested in a differentiation system it did not drive purified B cells to differentiate to PFC, either alone or when supplemented with a supernatant from concanavalin A-stimulated spleen cells (CAS). However, when both CAS and dextran sulfate (DXS) were supplied to the STM-stimulated cells, a large number of PFC resulted. DXT does not act by stimulating an additional, CAS-responsive B cell subset, since it has only a marginal effect upon 3 H-TdR uptake and does not increase the number of B cells in cycle when used together with STM. The authors that the two agents may be acting sequentially: STM stimulates the B cells to proliferate, and DXS drives the proliferating cells to become responsive to CAS. This suggests that the signals for B cell differentiation must consist of at least three activities: a trigger to stimulate the cells to proliferate, a factor to drive the cells to a BCDF-responsive state, and a BCDF that can drive the cells to secrete antibody

Comparison of the immunosuppressive effect of fractionated total lymphoid irradiation (TLI) vs conventional immunosuppression (CI) in renal cadaveric allotransplantation

International Nuclear Information System (INIS)

Waer, M.; Vanrenterghem, Y.; Ang, K.K.; van der Schueren, E.; Michielsen, P.; Vandeputte, M.

1984-01-01

Beginning in November 1981, eight patients with end stage diabetic nephropathy underwent renal cadaveric transplantation after TLI. Transplantation was done between 2 to 11 days after the end of a fractionated TLI to a total dose of 20 to 30 Gy. During the same observation period, 60 nondiabetic patients with end stage renal disease of different origin also received a cadaveric kidney graft, with a conventional regimen of immunosuppression that consists of anti-lymphocyte-globulin, tapering high doses of prednisone, and azathioprine. Phytohemagglutinin (PHA)-, concanavalin A (con A)-, and pokeweed mitogen (PWM)-induced blastogenesis, as well as the mixed lymphocyte reaction (MLR) and the cell-mediated lympholysis (CML) decreased progressively during the first months after conventional immunosuppression to 50% of the pretransplantation level, and remained there for the first year after transplantation. These tests were much more impaired after TLI and again no recovery occurred during the first year. In the clinic, the more profound immunosuppression in TLI patients was more frequently associated with viral infections (cytomegalovirus and herpes zoster). The incidence of rejections, however, was somewhat less frequent in the TLI-treated group and occurred significantly later. After TLI, the mean cumulative dose of steroids needed for kidney transplantation during the first year after transplantation could be substantially reduced

Highly Sensitive and Wide-Dynamic-Range Multichannel Optical-Fiber pH Sensor Based on PWM Technique.

Science.gov (United States)

Khan, Md Rajibur Rahaman; Kang, Shin-Won

2016-11-09

In this study, we propose a highly sensitive multichannel pH sensor that is based on an optical-fiber pulse width modulation (PWM) technique. According to the optical-fiber PWM method, the received sensing signal's pulse width changes when the optical-fiber pH sensing-element of the array comes into contact with pH buffer solutions. The proposed optical-fiber PWM pH-sensing system offers a linear sensing response over a wide range of pH values from 2 to 12, with a high pH-sensing ability. The sensitivity of the proposed pH sensor is 0.46 µs/pH, and the correlation coefficient R² is approximately 0.997. Additional advantages of the proposed optical-fiber PWM pH sensor include a short/fast response-time of about 8 s, good reproducibility properties with a relative standard deviation (RSD) of about 0.019, easy fabrication, low cost, small size, reusability of the optical-fiber sensing-element, and the capability of remote sensing. Finally, the performance of the proposed PWM pH sensor was compared with that of potentiometric, optical-fiber modal interferometer, and optical-fiber Fabry-Perot interferometer pH sensors with respect to dynamic range width, linearity as well as response and recovery times. We observed that the proposed sensing systems have better sensing abilities than the above-mentioned pH sensors.

Highly Sensitive and Wide-Dynamic-Range Multichannel Optical-Fiber pH Sensor Based on PWM Technique

Science.gov (United States)

Khan, Md. Rajibur Rahaman; Kang, Shin-Won

2016-01-01

In this study, we propose a highly sensitive multichannel pH sensor that is based on an optical-fiber pulse width modulation (PWM) technique. According to the optical-fiber PWM method, the received sensing signal’s pulse width changes when the optical-fiber pH sensing-element of the array comes into contact with pH buffer solutions. The proposed optical-fiber PWM pH-sensing system offers a linear sensing response over a wide range of pH values from 2 to 12, with a high pH-sensing ability. The sensitivity of the proposed pH sensor is 0.46 µs/pH, and the correlation coefficient R2 is approximately 0.997. Additional advantages of the proposed optical-fiber PWM pH sensor include a short/fast response-time of about 8 s, good reproducibility properties with a relative standard deviation (RSD) of about 0.019, easy fabrication, low cost, small size, reusability of the optical-fiber sensing-element, and the capability of remote sensing. Finally, the performance of the proposed PWM pH sensor was compared with that of potentiometric, optical-fiber modal interferometer, and optical-fiber Fabry–Perot interferometer pH sensors with respect to dynamic range width, linearity as well as response and recovery times. We observed that the proposed sensing systems have better sensing abilities than the above-mentioned pH sensors. PMID:27834865

Transistor Clamped Five-Level Inverter using Non-Inverting Double Reference Single Carrier PWM Technique for photovoltaic applications

DEFF Research Database (Denmark)

Bhaskar, Mahajan Sagar; Padmanaban, Sanjeevikumar; Fedák, Viliam

2017-01-01

in output waveform. Under-modulation (modulation Index = 0.85), unity (modulation Index =1) and over-modulation (modulation Index = 1.25) PWM signal is obtained to drive control switches. Simulation results will confirm the functionality, design and operation of the proposed MLI and NIDRSC PWM Technique....

Control Strategy of PWM Rectifiers Connected to Unbalanced Grids

Czech Academy of Sciences Publication Activity Database

Bejvl, Martin; Švec, J.; Tlustý, J.; Valouch, V.

-, č. 11 (2013) ISSN 2172-038X. [International Conference on Renewable Energies and Power Quality (ICREPQ´13). Bilbao, 20.03.2013-22.03.2013] Institutional support: RVO:61388998 Keywords : electric power system * PWM rectifier * dc voltage ripple Subject RIV: JA - Electronics ; Optoelectronics, Electrical Engineering

Research on Single-Phase PWM Converter with Reverse Conducting IGBT Based on Loss Threshold Desaturation Control

Directory of Open Access Journals (Sweden)

Xianjin Huang

2017-11-01

Full Text Available In the application of vehicle power supply and distributed power generation, there are strict requirements for the pulse width modulation (PWM converter regarding power density and reliability. When compared with the conventional insulated gate bipolar transistor (IGBT module, the Reverse Conducting-Insulated Gate Bipolar Transistor (RC-IGBT with the same package has a lower thermal resistance and higher current tolerance. By applying the gate desaturation control, the reverse recovery loss of the RC-IGBT diode may be reduced. In this paper, a loss threshold desaturation control method is studied to improve the output characteristics of the single-phase PWM converter with a low switching frequency. The gate desaturation control characteristics of the RC-IGBT’s diode are studied. A proper current limit is set to avoid the ineffective infliction of the desaturation pulse, while the bridge arm current crosses zero. The expectation of optimized loss decrease is obtained, and the better performance for the RC-IGBTs of the single-phase PWM converter is achieved through the optimized desaturation pulse distribution. Finally, the improved predictive current control algorithm that is applied to the PWM converter with RC-IGBTs is simulated, and is operated and tested on the scaled reduced power platform. The results prove that the gate desaturation control with the improved predictive current algorithm may effectively improve the RC-IGBT’s characteristics, and realize the stable output of the PWM converter.

Parallel implementation of DNA sequences matching algorithms using PWM on GPU architecture.

Science.gov (United States)

Sharma, Rahul; Gupta, Nitin; Narang, Vipin; Mittal, Ankush

2011-01-01

Positional Weight Matrices (PWMs) are widely used in representation and detection of Transcription Factor Of Binding Sites (TFBSs) on DNA. We implement online PWM search algorithm over parallel architecture. A large PWM data can be processed on Graphic Processing Unit (GPU) systems in parallel which can help in matching sequences at a faster rate. Our method employs extensive usage of highly multithreaded architecture and shared memory of multi-cored GPU. An efficient use of shared memory is required to optimise parallel reduction in CUDA. Our optimised method has a speedup of 230-280x over linear implementation on GPU named GeForce GTX 280.

Analysis of Peak-to-Peak Current Ripple Amplitude in Seven-Phase PWM Voltage Source Inverters

Directory of Open Access Journals (Sweden)

Gabriele Grandi

2013-08-01

Full Text Available Multiphase systems are nowadays considered for various industrial applications. Numerous pulse width modulation (PWM schemes for multiphase voltage source inverters with sinusoidal outputs have been developed, but no detailed analysis of the impact of these modulation schemes on the output peak-to-peak current ripple amplitude has been reported. Determination of current ripple in multiphase PWM voltage source inverters is important for both design and control purposes. This paper gives the complete analysis of the peak-to-peak current ripple distribution over a fundamental period for multiphase inverters, with particular reference to seven-phase VSIs. In particular, peak-to-peak current ripple amplitude is analytically determined as a function of the modulation index, and a simplified expression to get its maximum value is carried out. Although reference is made to the centered symmetrical PWM, being the most simple and effective solution to maximize the DC bus utilization, leading to a nearly-optimal modulation to minimize the RMS of the current ripple, the analysis can be readily extended to either discontinuous or asymmetrical modulations, both carrier-based and space vector PWM. A similar approach can be usefully applied to any phase number. The analytical developments for all different sub-cases are verified by numerical simulations.

Power Electronic Transformer based Three-Phase PWM AC Drives

Science.gov (United States)

Basu, Kaushik

A Transformer is used to provide galvanic isolation and to connect systems at different voltage levels. It is one of the largest and most expensive component in most of the high voltage and high power systems. Its size is inversely proportional to the operating frequency. The central idea behind a power electronic transformer (PET) also known as solid state transformer is to reduce the size of the transformer by increasing the frequency. Power electronic converters are used to change the frequency of operation. Steady reduction in the cost of the semiconductor switches and the advent of advanced magnetic materials with very low loss density and high saturation flux density implies economic viability and feasibility of a design with high power density. Application of PET is in generation of power from renewable energy sources, especially wind and solar. Other important application include grid tied inverters, UPS e.t.c. In this thesis non-resonant, single stage, bi-directional PET is considered. The main objective of this converter is to generate adjustable speed and magnitude pulse width modulated (PWM) ac waveforms from an ac or dc grid with a high frequency ac link. The windings of a high frequency transformer contains leakage inductance. Any switching transition of the power electronic converter connecting the inductive load and the transformer requires commutation of leakage energy. Commutation by passive means results in power loss, decrease in the frequency of operation, distortion in the output voltage waveform, reduction in reliability and power density. In this work a source based partially loss-less commutation of leakage energy has been proposed. This technique also results in partial soft-switching. A series of converters with novel PWM strategies have been proposed to minimize the frequency of leakage inductance commutation. These PETs achieve most of the important features of modern PWM ac drives including 1) Input power factor correction, 2) Common

A DEMODULATOR OF PWM SIGNALS GENERATED FOR A DIGITAL ACCELEROMETER IS DEVELOPED USING A MICROCONTROLLER UN DEMODULADOR DE SEÑALES PWM GENERADAS POR UN ACELERÓMETRO DIGITAL ES DESARROLLADO USANDO UN MICROCONTROLADOR

Directory of Open Access Journals (Sweden)

Eduardo Pérez Lobato

2006-08-01

Full Text Available This paper presents the use of a microcontroller to demodulate two Pulse Width Modulated (PWM signals which are being generated by a digital accelerometer, to obtain their pulse widths and transmit them serially to a parallel port of a general purpose computer.Esta publicación presenta el uso de un microcontrolador para demodular dos señales PWM que están siendo generadas por un acelerómetro digital, obtener sus anchos y enviarlas en forma serial al puerto paralelo de un computador de propósitos generales.

Effects of metal ions on cyprinid fish immune response: In vitro effects of Zn2+ and Mn2+ on the mitogenic response of carp pronephros lymphocytes

International Nuclear Information System (INIS)

Ghanmi, Z.; Rouabhia, M.; Othmane, O.; Deschaux, P.A.

1989-01-01

Lymphocytes from the pronephros of carp (Cyprinus carpio L) have been subjected to transformation by mitogens, concanavalin A (Con A), phytohemagglutinin (PHA), and lipopolysaccharides (LPS), with Zn or Mn at varying concentrations. Addition of Zn 2+ (10(-7) to 10(-3) M) to mitogen-stimulated T and B cells enhanced [ 3 H]thymidine incorporation. Addition of 10(-5) M Zn 2+ inhibited the response to Con A, PHA, and LPS. At this concentration, Zn was toxic. Addition of Mn2+ (10(-7) to 10(-3) M) to mitogen-stimulated lymphocytes enhanced [ 3 H]thymidine incorporation. This effect was observed with Con A- and PHA-stimulated lymphocytes, but not with LPS-stimulated lymphocytes. In contrast, addition of 10(-1) M Mn 2+ to lymphocyte cultures exerted an inhibitor on the response to Con A or to PHA, while the response to LPS was unaffected. Addition of 10(-1) M Mn 2+ to Con A- or PHA-stimulated cultures at different times after initiation of stimulation indicated that Mn 2+ was inhibitory only when it was added before the first 16 hr of cultures. The inhibition induced by 10(-1) M Mn2+ could be reversed by adding 2 mM CaCl 2 to the culture

A high efficiency PWM CMOS class-D audio power amplifier

Energy Technology Data Exchange (ETDEWEB)

Zhu Zhangming; Liu Lianxi; Yang Yintang [Institute of Microelectronics, Xidian University, Xi' an 710071 (China); Lei Han, E-mail: zmyh@263.ne [Xi' an Power-Rail Micro Co., Ltd, Xi' an 710075 (China)

2009-02-15

Based on the difference close-loop feedback technique and the difference pre-amp, a high efficiency PWM CMOS class-D audio power amplifier is proposed. A rail-to-rail PWM comparator with window function has been embedded in the class-D audio power amplifier. Design results based on the CSMC 0.5 mum CMOS process show that the max efficiency is 90%, the PSRR is -75 dB, the power supply voltage range is 2.5-5.5 V, the THD+N in 1 kHz input frequency is less than 0.20%, the quiescent current in no load is 2.8 mA, and the shutdown current is 0.5 muA. The active area of the class-D audio power amplifier is about 1.47 x 1.52 mm{sup 2}. With the good performance, the class-D audio power amplifier can be applied to several audio power systems.

A high efficiency PWM CMOS class-D audio power amplifier

International Nuclear Information System (INIS)

Zhu Zhangming; Liu Lianxi; Yang Yintang; Lei Han

2009-01-01

Based on the difference close-loop feedback technique and the difference pre-amp, a high efficiency PWM CMOS class-D audio power amplifier is proposed. A rail-to-rail PWM comparator with window function has been embedded in the class-D audio power amplifier. Design results based on the CSMC 0.5 μm CMOS process show that the max efficiency is 90%, the PSRR is -75 dB, the power supply voltage range is 2.5-5.5 V, the THD+N in 1 kHz input frequency is less than 0.20%, the quiescent current in no load is 2.8 mA, and the shutdown current is 0.5 μA. The active area of the class-D audio power amplifier is about 1.47 x 1.52 mm 2 . With the good performance, the class-D audio power amplifier can be applied to several audio power systems.

A high efficiency PWM CMOS class-D audio power amplifier

Science.gov (United States)

Zhangming, Zhu; Lianxi, Liu; Yintang, Yang; Han, Lei

2009-02-01

Based on the difference close-loop feedback technique and the difference pre-amp, a high efficiency PWM CMOS class-D audio power amplifier is proposed. A rail-to-rail PWM comparator with window function has been embedded in the class-D audio power amplifier. Design results based on the CSMC 0.5 μm CMOS process show that the max efficiency is 90%, the PSRR is -75 dB, the power supply voltage range is 2.5-5.5 V, the THD+N in 1 kHz input frequency is less than 0.20%, the quiescent current in no load is 2.8 mA, and the shutdown current is 0.5 μA. The active area of the class-D audio power amplifier is about 1.47 × 1.52 mm2. With the good performance, the class-D audio power amplifier can be applied to several audio power systems.

Elimination of output voltage oscillations in DC-DC converter using PWM with PI controller

Directory of Open Access Journals (Sweden)

Sreenivasappa Veeranna Bhupasandra

2010-01-01

Full Text Available In this paper the SIMULINK model of a PWM controlled DC-DC converter is modeled using switching function concept to control the speed of the DC motor. The presence of the voltage oscillation cycles due to higher switching frequency in the DC-DC converter is identified. The effect of these oscillations on the output voltage of the converter, Armature current, Developed torque and Speed of the DC motor is analyzed. In order to minimize the oscillation cycles the PI controller is proposed in the PWM controller.

The PWM strategies of grid-connected distributed generation active NPC inverters

DEFF Research Database (Denmark)

Ma, Lin; Xinmin, Jin; Kerekes, Tamas

2009-01-01

The Neutral Point Clamped topology due to high efficiency, low leakage current and EMI, its integration is widely used in the distributed generation (DG) systems. However the main disadvantage of the NPC inverter is given by an unequal distribution of the losses in the semiconductor devices, which...... leads to an unequal distribution of temperature. By using the Active NPC topology, the power losses distribution problem is alleviated. The modulation strategy is a key issue for losses distribution in this topology. In this paper two known strategies are discussed and a new proposed PWM strategy......, namely the Adjustable Losses Distribution (ALD) PWM strategy is proposed for better losses distribution in the Active NPC (ANPC) topology. Simulations using Simulink and the PLECS toolbox have been done for evaluating efficiency of different NPC topologies and some experimental results are presented...

Liquid scintillation vial for radiometric assay of lymphocyte carbohydrate metabolism in response to mitogens

International Nuclear Information System (INIS)

Tran, N.; Wagner, H.N. Jr.

1978-01-01

We have demonstrated that mitogens--i.e., PHA and Con.A--stimulate lymphocyte carbohydrate metabolism using a liquid-scintillation vial with conventional liquid-scintillation detectors. The results showed that this enclosed system can be useful for development of rapid in vitro tests of lymphocytes immune responsiveness, as well as for radiometric detection of bacterial growth in various gaseous atmospheres

Development of a current-type PWM converter with high power factor. 1

International Nuclear Information System (INIS)

Miura, Yushi; Matsukawa, Makoto; Miyachi, Kengo; Kimura, Toyoaki

1998-01-01

A power supply system for superconducting poloidal field coils of a next generation tokamak-type fusion device can be operated on the relatively low voltage for the duration of discharge except the plasma initiation. In the case of the conventional phase-controlled thyristor converters are adopted in such a system, the input power factor would be low in average, and a reactive power fluctuation caused by the change of DC output voltage may produce serious effects on the commercial transmission line. From the above viewpoint, a current-type PWM (Pulse Width Modulation) converter, which can work with the power factor of unity for the input power, is regarded as one of the promising candidates of the converters for the power supplies of next generation fusion devices. Hence, a 100kW-class current-type PWM converter has been developed by using IGBT (Insulated Gate Bipolar Transistor) as switching devices. In this development, the basic performance has been preliminary investigated whether this converter is applicable to the power supply for the next generation fusion device. In addition, two different PWM control methods were examined whether these methods can realize a unit power factor and suppress the transient oscillation of converter input current at the same time in case that the reference of DC output current is changed rapidly. (author)

Shunt PWM advanced var compensators based on voltage source inverters for Facts applications

Energy Technology Data Exchange (ETDEWEB)

Barbosa, Pedro G; Misaka, Isamu; Watanabe, Edson H [Universidade Federal, Rio de Janeiro, RJ (Brazil). Coordenacao dos Programas de Pos-graduacao de Engenharia

1994-12-31

Increased attention has been given to improving power system operation. This paper presents modeling, analysis and design of reactive shunt power compensators based on PWM-Voltage Source Inverters (Pulse Width Modulation -Voltage Source Inverters). (Pulse Width Modulation - Voltage Source Inverters). The control algorithm is based on new concepts of instantaneous active and reactive power theory. The objective is to show that with a small capacitor in the side of a 3-phase PWM-VSI it is possible to synthesize a variable reactive (capacitive or inductive) device. Design procedures and experimental results are presented. The feasibility of this method was verified by digital simulations and measurements on a small scale model. (author) 9 refs., 12 figs.

The Effect of IL-4 Gene Polymorphisms on Cytokine Production in Patients with Chronic Periodontitis and in Healthy Controls

Directory of Open Access Journals (Sweden)

Jirina Bartova

2014-01-01

Full Text Available Chronic periodontitis (CP is an inflammatory disease of the teeth-supporting tissues in which genetic predisposition, dental plaque bacteria, and immune mechanisms all play important roles. The aim of this study was to evaluate the occurrence of IL-4 gene polymorphisms in chronic periodontitis and to investigate the association between polymorphisms and cytokines production after bacterial stimulation. Sixty-two subjects (47 CP patients and 15 healthy controls with detected two polymorphisms in the IL-4 gene (-590C/T and intron 3 VNTR were examined. Production of cytokines (IL-1α, IL-1β, IL-4, IL-5, IL-6, IL-10, IL-17, TNFα, INFγ, and VEGF was studied after in vitro stimulation of isolated peripheral blood by mitogens (Pokeweed mitogen, Concanavalin A, dental plaque bacteria (Aggregatibacter actinomycetemcomitans, Tannerella forsythia, Porphyromonas gingivalis, and Prevotella intermedia, and Heat Shock Protein (HSP 70 by the Luminex multiplex cytokine analysis system. The results were correlated with IL-4 genotypes in patients with CP and healthy controls. The mononuclear cells isolated from peripheral blood of CP patients with selected IL-4 polymorphisms significantly altered the production of IFNγ, IL-10, IL-1β, IL-1α, TNFα, and IL-6 after stimulation by HSP 70 or selected bacteria (from P<0.001 to P<0.05. IL-4 gene polymorphisms may influence the function of mononuclear cells to produce not only interleukin-4 but also other cytokines, especially in patients with CP.

GENETIC ALGORITHM BASED SOLUTION IN PWM CONVERTER SWITCHING FOR VOLTAGE SOURCE INVERTER FEEDING AN INDUCTION MOTOR DRIVE

Directory of Open Access Journals (Sweden)

V. Jegathesan

2017-11-01

Full Text Available This paper presents an efficient and reliable Genetic Algorithm based solution for Selective Harmonic Elimination (SHE switching pattern. This method eliminates considerable amount of lower order line voltage harmonics in Pulse Width Modulation (PWM inverter. Determination of pulse pattern for the elimination of some lower order harmonics of a PWM inverter necessitates solving a system of nonlinear transcendental equations. Genetic Algorithm is used to solve nonlinear transcendental equations for PWM-SHE. Many methods are available to eliminate the higher order harmonics and it can be easily removed. But the greatest challenge is to eliminate the lower order harmonics and this is successfully achieved using Genetic Algorithm without using Dual transformer. Simulations using MATLABTM and Powersim with experimental results are carried out to validate the solution. The experimental results show that the harmonics up to 13th were totally eliminated.

The harmonic composition of the output voltage of a rectifier unit with a PWM voltage booster converter.

OpenAIRE

ПАНЧЕНКО, В В

2015-01-01

The author investigates a rectifier unit constructed on the basis of cascade connection of the main non-controlled m-pulse rectifier and PWM voltage booster converter. The research presents the analysis of the harmonic composition of the output voltage of a rectifier unit with a PWM voltage booster converter on completely controlled keys. The dependence of the relative harmonic amplitude on the commutation corner is defined. The estimation of a rectifier unit electromagnetic compatibility wit...

Three Phase Six-Switch PWM Buck Rectifier with Power Factor Improvement

DEFF Research Database (Denmark)

Zafar Ullah Khan, M; Mohsin Naveed, M.; Hussain, Dil Muhammad Akbar

2013-01-01

Conventional Phase Controlled Rectifier injects low order current harmonics into the AC mains. Large size filtering components are required to attenuate these harmonics. In this paper, Three Phase Six-Switch PWM Buck Rectifier[1] is presented which operates at nearly unity power factor and provides...

Application of digital PWM technology in current transducers

International Nuclear Information System (INIS)

Liu Huifang; Hu Zhimin; Li Rui

2012-01-01

With the development of DSP technology and mature use of PID technology,, a new program for DC or AC signal measurement is proposed. Combined with the DSP chip timer module and PID algorithm, PWM signals are generated to control the feedback circuit for the compensation current. Finally the measured current value can be obtained according to the ampere-turns compensation current and the measured current. Studies have shown that this technology enables new current transducers have high stability. (authors)

Lack of direct mitogenic activity of dichloroacetate and trichloroacetate in cultured rat hepatocytes

International Nuclear Information System (INIS)

Walgren, Jennie L.; Kurtz, David T.; McMillan, JoEllyn M.

2005-01-01

Dichloroacetate (DCA) and trichloroacetate (TCA) are hepatocarcinogenic metabolites of the common groundwater contaminant, 1,1,2-trichloroethylene. DCA and TCA have been shown to induce hepatocyte proliferation in vivo, but it is not known if this response is the result of direct mitogenic activity or whether cell replication occurs indirectly in response to tissue injury or inflammation. In this study we used primary cultures of rat hepatocytes, a species susceptible to DCA- but not TCA-induced hepatocarcinogenesis, to determine whether DCA and TCA are direct hepatocyte mitogens. Rat hepatocytes, cultured in growth factor-free medium, were treated with 0.01-1.0 mM DCA or TCA for 10-40 h; cell replication was then assessed by measuring incorporation of 3 H-thymidine into DNA and by cell counts. DCA or TCA treatment did not alter 3 H-thymidine incorporation in the cultured hepatocytes. Although an increase in cell number was not observed, DCA treatment significantly abrogated the normal background cell loss, suggesting an ability to inhibit apoptotic cell death in primary hepatocyte cultures. Furthermore, treatment with DCA synergistically enhanced the mitogenic response to epidermal growth factor. The data indicate that DCA and TCA are not direct mitogens in hepatocyte cultures, which is of interest in view of their ability to stimulate hepatocyte replication in vivo. Nevertheless, the synergistic enhancement of epidermal growth factor-induced hepatocyte replication by DCA is of particular interest and warrants further study

Stator insulation systems for medium voltage PWM drives fed motors

International Nuclear Information System (INIS)

Gao, G.; Chen, W.

2005-01-01

This paper presents the partial results of a research project that studied the impact of medium voltage PWM ASD (adjustable speed drives) on motor stator insulation system. The findings from this study/ investigation have aided designers to improve the robustness of the insulation system used for ASD-fed motors, based on accelerated laboratory tests. (author)

Interleaved Boost-Half-Bridge Dual–Input DC-DC Converter with a PWM plus Phase-Shift Control for Fuel Cell Applications

DEFF Research Database (Denmark)

Zhang, Zhe; Andersen, Michael A. E.

2013-01-01

This paper presents an isolated dual-input DC-DC converter with a PWM plus phase-shift control for fuel cell hybrid energy systems. The power switches are controlled by phase shifted PWM signals with a variable duty cycle, and thus the two input voltages as well as the output voltage can...

Microcontroller based PWM controlled four switch three phase inverter fed induction motor drive

Directory of Open Access Journals (Sweden)

Mohanty Kant Nalin

2010-01-01

Full Text Available This paper presents PIC microcontroller based PWM inverter controlled four switch three phase inverter (FSTPI fed Induction Motor drive. The advantage of this inverter that uses of 4 switches instead of conventional 6 switches is lesser switching losses, lower electromagnetic interference (EMI, less complexity of control algorithms and reduced interface circuits. Simulation and experimental work are carried out and results presented to demonstrate the feasibility of the proposed approach. Simulation is carried out using MATLAB SIMULINK and in the experimental work a prototype model is built to verify the simulation results. PIC microcontroller (PIC 16F877A is used to generate the PWM pulses for FSTPI to drive the 0.5 hp 3-phase Induction Motor.

Step-down switched-capacitor quasi-resonant PWM converter with continuous conversion ratio

NARCIS (Netherlands)

Turhan, M.; Hendrix, M.A.M.; Duarte, J.L.

2015-01-01

Inherent disadvantages of conventional switched-capacitor converters (SCC) are their discrete conversion ratio and inefficient energy transfer. In order to soften these downsides, a step-down switched-capacitor quasi-resonant PWM converter is proposed. The operation modes and steady-state

Modeling and the analysis of control logic for a digital PWM controller based on a nano electronic single electron transistor

Directory of Open Access Journals (Sweden)

Rathnakannan Kailasam

2008-01-01

Full Text Available This paper describes the modelling and the analysis of control logic for a Nano-Device- based PWM controller. A comprehensive simple SPICE schematic model for Single Electron transistor has been proposed. The operation of basic Single Electron Transistor logic gates and SET flip flops were successfully designed and their performances analyzed. The proposed design for realizing the logic gates and flip-flops is used in constructing the PWM controller utilized for switching the buck converter circuit. The output of the converter circuit is compared with reference voltage, and when the error voltage and the reference are matched the latch is reset so as to generate the PWM signal. Due to the simplicity and accuracy of the compact model, the simulation time and speed are much faster, which makes it potentially applicable in large-scale circuit simulation. This study confirms that the SET-based PWM controller is small in size, consumes ultra low power and operates at high speeds without compromising any performance. In addition these devices are capable of measuring charges of extremely high sensitivity.

Combined time-lapse cinematography and immuno-electron microscopy.

Science.gov (United States)

Balfour, B M; Goscicka, T; MacKenzie, J L; Gautam, A; Tate, M; Clark, J

1990-04-01

A method was developed to record interactions between mobile non-adherent immunocytes by time-lapse cinematography and then to study the same cells by immuno-electron microscopy, using monoclonal antibodies against surface components. For this purpose a modified stage was designed to fit an inverted microscope. The attachment included a device to cool the culture chamber with N2 gas, a micro-injector for monoclonal antibody and immuno-gold treatment, and two pairs of washing needles to change the medium without disturbance. The technique was first employed to study the formation of aggregates around the antigen-presenting cells in cultures containing cells from hyper-immunized animals. Recently peripheral blood cells from normal subjects and patients with immune deficiency syndromes were stimulated with pokeweed mitogen, cluster formation was recorded, and the cells were processed for immuno-electron microscopy.

An improved fault-tolerant control scheme for PWM inverter-fed induction motor-based EVs.

Science.gov (United States)

Tabbache, Bekheïra; Benbouzid, Mohamed; Kheloui, Abdelaziz; Bourgeot, Jean-Matthieu; Mamoune, Abdeslam

2013-11-01

This paper proposes an improved fault-tolerant control scheme for PWM inverter-fed induction motor-based electric vehicles. The proposed strategy deals with power switch (IGBTs) failures mitigation within a reconfigurable induction motor control. To increase the vehicle powertrain reliability regarding IGBT open-circuit failures, 4-wire and 4-leg PWM inverter topologies are investigated and their performances discussed in a vehicle context. The proposed fault-tolerant topologies require only minimum hardware modifications to the conventional off-the-shelf six-switch three-phase drive, mitigating the IGBTs failures by specific inverter control. Indeed, the two topologies exploit the induction motor neutral accessibility for fault-tolerant purposes. The 4-wire topology uses then classical hysteresis controllers to account for the IGBT failures. The 4-leg topology, meanwhile, uses a specific 3D space vector PWM to handle vehicle requirements in terms of size (DC bus capacitors) and cost (IGBTs number). Experiments on an induction motor drive and simulations on an electric vehicle are carried-out using a European urban driving cycle to show that the proposed fault-tolerant control approach is effective and provides a simple configuration with high performance in terms of speed and torque responses. Copyright © 2013 ISA. Published by Elsevier Ltd. All rights reserved.

The mitogenic activities of bean proteins determined by assay of the incorporation of sup(3)H - thymidine by human lymphocytes

International Nuclear Information System (INIS)

Derbyshire, E.; Carvalho, M.T.V.; Vitti, D.M.S.; Costa, C.P. da

1988-01-01

The proteins in a saline extract from cotyledons of the bean cultivar Goiano precoce included a protein with electrophoretic mobility equal to that of a commercial preparation of bean mitogen. The crude extract stimulated the incorporation of sup(3)H-tymidine by cultures of human lymphocytes at concentrations of extracted protein from 30 mu g - 300 mu g/culture, and the existence of an optimal concentration in the vicinity of 175 mu g/culture was indicated by the data. The range of active concentrations and the optimal concentration of the heterogeneous extract were 12-15 times greater than the corresponding values obtained when the commercial mitogen was employed. Microscopic examinations showed the presence of blast cells and mitotic figures only in cultures which included seed extract or commercial mitogen. (author)

Rachycentron canadum (cobia) lectin promoted mitogenic response in mice BALB/c splenocytes.

Science.gov (United States)

Coriolano, M C; de Melo, C M L; Santos, A J G; Pereira, V R A; Coelho, L C B B

2012-12-01

The mitogenic lectins are invaluable tools to study the biochemical changes associated with lymphocyte activation and proliferation of various immune cells. Rachycentron canadum lectin (RcaL) was detected and purified from serum of cobia fish. The aim of this study was to evaluate the proliferative response and cytokine production in splenocytes of mice in vitro stimulated with RcaL lectin; Canavalia ensiformis lectin (Con A) was used as positive control. A high proliferation index was induced by RcaL in relation to control cells. Furthermore, RcaL induced higher IL-2 and IL-6 production in relation to control. The cell viability was 90% in splenocytes treated with RcaL lectin, but RcaL promoted significant late apoptosis after 24 and 48 h in relation to control. RcaL induced proliferative responses suggesting that this lectin can be used as a mitogenic agent in immunostimulatory assays. © 2012 The Authors. Scandinavian Journal of Immunology © 2012 Blackwell Publishing Ltd.

A Review on Direct Power Control for Applications to Grid Connected PWM Converters

Directory of Open Access Journals (Sweden)

T. A. Trivedi

2015-08-01

Full Text Available The Direct Power Control strategy has become popular as an alternative to the conventional vector oriented control strategy for grid connected PWM converters. In this paper, Direct Power Control as applied to various applications of grid connected converters is reviewed. The Direct Power Control for PWM rectifiers, Grid Connected DC/AC inverters applications such as renewable energy sources interface, Active Power Filters, Doubly Fed Induction Generators and AC-DC-AC converters are discussed. Control strategies such as Look-Up table based control, predictive control, Virtual Flux DPC, Model based DPC and DPC-Space Vector Modulation are critically reviewed. The effects of various key parameters such as selection of switching vector, sampling time, hysteresis band and grid interfacing on performance of direct power controlled converters are presented.

Progressive decrement PWM algorithm for minimum mean square error inverter output voltage

International Nuclear Information System (INIS)

Ghaeb, J.A.; Smadi, M.A.; Ababneh, M.

2011-01-01

Highlights: → The main contribution of this work is to provide a better performance for the power inverter operation. → The proposed technique splits the determined original pulse-width of an inverter operation in to many pulses. → The new approach extends the central pulse and shrinks the exterior pulses. → This is leading to an inverter output cycle close to the sinusoidal form of fewer harmonics. - Abstract: The paper proposes two modulation techniques for the power inverter. These new techniques are named progressive decrement PWM algorithm (PDPA) and progressive increment PWM algorithm (PIPA). Both techniques take the determined original pulse-width of an inverter operation and split it to many pulses. In the PDPA technique, the largest width is given to the middle pulse and the width of the boundary pulses is reduced progressively starting from the first boundary-pulse toward the last boundary-pulse. In the PIPA technique, there is a gradual increment instead of decrement. The two techniques have been proved that it can maintain the original pulse-width of the inverter operation. The new approach PDPA extends the central pulse and shrinks the exterior pulses, leading to an inverter output cycle close to the sinusoidal form of fewer harmonic contents. Simulation results are performed to evaluate the performances of the proposed techniques: PDPA and PIPA and to compare them with the well known methods. The main contribution of the proposed PDPA technique is that it provides a better performance for the most harmonic orders compared to the well established sinusoidal PWM technique.

Comparison of selected immunological parameters in silver and polar foxes

International Nuclear Information System (INIS)

Kostro, K.; Woloszyn, S.

1996-01-01

The aim of the work was to compare selected nonspecific immunological parameters in silver and polar foxes. It was found that out of three mitogens (Con A, La and PWM) only Con A stimulated the strongest lymphocyte proliferation in both species of foxes. Mean stimulation indices and the absolute values of incorporated thymidine were significantly higher in polar foxes. The average percentages of phagocytes and the fatal indices of neutrophils were comparable in both species of foxes, while the mean value of the phagocyte index was much higher in the silver fox. However, in polar foxes a higher concentration of lysozyme in the blood serum was found. The differences in the parameters may influence the susceptibility of these foxes to some infections already at the level of nonspecific primary response. (author)

Synchronised PWM Schemes for Three-level Inverters with Zero Common-mode Voltage

DEFF Research Database (Denmark)

Oleschuk, Valentin; Blaabjerg, Frede

2002-01-01

This paper presents results of analysis and comparison of novel synchronised schemes of pulsewidth modulation (PWM), applied to three-level voltage source inverters with control algorithms providing elimination of the common-mode voltage. The proposed approach is based on a new strategy of digital...

In vitro X-ray irradiation of human peripheral blood T lymphocytes enhances suppressor function

International Nuclear Information System (INIS)

Ogawa, H.; Tsunematsu, T.

1983-01-01

The effect of in vitro X-ray irradiation on human peripheral blood T lymphocytes was studied with regard to their suppressor activity related to the concanavalin A (Con A)-induced suppressor system. To generate suppressor T lymphocytes, purified human T lymphocytes were incubated for 3 days in the first culture, with or without Con A. These lymphocytes were irradiated with various doses of X-ray before, mid or after the culture. After doing a second culture for 6 days, the suppressive influence of these cells on T lymphocyte proliferation rates stimulated with allogeneic mononuclear cells, and B lymphocyte proliferation rates stimulated with pokeweed mitogen was measured. Irradiation of cultures to which Con A had not been added induced much the same level of suppressor activity as seen in the cultures with Con A. The suppressor activity gradually increased with time from the irradiation to the suppressor cell assay. Suppressor T lymphocytes were resistant to X-ray irradiation and independent of DNA synthesis. However, irradiation-induced enhancement was minimal in cultures incubated with con A, regardless of the irradiation time. (author)

A ZVT–ZCT PWM synchronous buck converter with a simple passive auxiliary circuit for reduction of losses and efficiency enhancement

Directory of Open Access Journals (Sweden)

S. Shiva Kumar

2015-06-01

Full Text Available In this paper, a Zero-Voltage-Transition (ZVT–Zero-Current Transition (ZCT Pulse-width Modulated (PWM synchronous buck converter (SBC, with a simple passive auxiliary circuit is proposed, which reduces the stresses and improves the efficiency by pacifying the conduction losses compared to a traditional PWM converter, typically suitable for photovoltaic applications. The important design feature of ZVT–ZCT PWM SBC converters is placement of resonant components that mollifies the conduction losses. Due to the ZVT–ZCT, the resonant components with low values are used, thereby resulting in the increase of switching frequency. The ZVT–ZCT operation of the proposed converter is presented through theoretical analysis. The characteristics of the proposed converter are verified with the simulation in the PSIM co-simulated with MATLAB/SIMULINK environment and implemented experimentally.

Math Model and Calculation Analysis of Inter-harmonic of Double PWM Speed Control System in Distribution Network

Directory of Open Access Journals (Sweden)

Yang Wen-Huan

2014-11-01

Full Text Available Aiming at the problem that the distribution network voltage will fluctuate because of the inter-harmonic currents injected into the network by double PWM speed control system when regulating the speed of the asynchronous motor, we established the inter-harmonic current math model of double PWM speed control system according to switching function based on a real bridge crane. The distribution law of the inter-harmonic is got by calculating the grid-side currents and their spectrum while letting the motor run at different quadrants and frequencies. The result which is verified by simulation and experiment shows that the content of the inter harmonic currents is more than that of harmonic currents in double PWM speed control system, the frequency of the inter harmonics of the grid-side current mainly focus on the scope lower than the fundamental frequency, and when the motor runs at low frequencies, the THD of the grid-side current is high. The result has verified the reason why the voltage of a bridge crane distribution system of a deepwater port in Shanghai flickers.

Power electronic converters PWM strategies and current control techniques

CERN Document Server

Monmasson, Eric

2013-01-01

A voltage converter changes the voltage of an electrical power source and is usually combined with other components to create a power supply. This title is devoted to the control of static converters, which deals with pulse-width modulation (PWM) techniques, and also discusses methods for current control. Various application cases are treated. The book is ideal for professionals in power engineering, power electronics, and electric drives industries, as well as practicing engineers, university professors, postdoctoral fellows, and graduate students.

The quiescent and mitogen stimulated peripheral blood mononuclear cells after gamma irradiation and their P53, P21 and H2AX expression

International Nuclear Information System (INIS)

Vilasova, Z.; Vavrova, J.; Sinkorova, Z.; Tichy, A.; Oesterreicher, J.; Rezacova, M.; Zoelzer, F.

2008-01-01

The aim of this study was to compare reaction of quiescent and proliferating PHA (mitogenic lectin phytohemagglutinin)-stimulated human peripheral blood mononuclear cells (PBMCs) to γ-irradiation and analyze changes of proteins related to repair if DNA damage and apoptosis, such as γH2A.X, p53 and its phosphorylations on serine 15 and 392, and p21. Protein changes induced by radiation are different in quiescent and stimulated PBMCs. W e analyzed changes in proteins related to DNA damage repair and apoptosis using the western blot method in quiescent and stimulated PBMCs. Western blot technique can detect γH2A.X increase only at later times, when the phosphorylation of H2A.X is related to the onset of apoptosis (24-72 h after irradiation by the dose of 4 Gy). The level of H2A.X phosphorylation increased after stimulation of PBMC by PHA (72 h, 10 μg/ml) and as shown here it was detectable by western blot analysis. The increase in γH2A.X that we detected by western blot 4 h after irradiation of stimulated lymphocytes was dose dependent. It can be concluded that measurement of γH2A.X during the first hours after the irradiation is a good marker of the received dose of radiation. We compared the dynamics of p53 induction after irradiation by IR in both quiescent and stimulated lymphocytes. p53 increase was observed only in stimulated lymphocytes, as was p53 phosphorylation at serines-392 and -15. The increase in the amount of p53 was not dose-dependent 4 h after the irradiation. On the other hand, phosphorylation of p53 at serine-15 analyzed 4 h after the irradiation is dose-dependent over the studied dose range. Despite the fact that p53 was not detected in quiescent lymphocytes and a reaction to irradiation was not observed either, p21 levels increased after irradiation in both quiescent and stimulated lymphocytes in a dose-dependent manner. IR induces phosphorylation of p53 at both serines-15 and -392 in PHA stimulated human lymphocytes. However

Loss Distribution Analysis of Three-Level Active Neutral-Point-Clamped (3L-ANPC) Converter with Different PWM Strategies

DEFF Research Database (Denmark)

Zhang, Gang; Yang, Yongheng; Iannuzzo, Francesco

2016-01-01

The three-level (3L) Active Neutral-Point-Clamped (ANPC) topology has been introduced to resolve the uneven loss distribution issue in the classical 3L Neutral-Point-Clamped (NPC) topology. This Pulse-Width-Modulation (PWM) strategy is then an important means to fully explore the potential benefits...... are separated in order to improve the loss distribution among the power devices. A comparison between the proposed strategy and other major PWM strategies for the loss distribution is also carried out in this paper. Benchmarking results show that the proposed strategy has effective and superior performance...

Angiotensin II regulation of neuromodulation: downstream signaling mechanism from activation of mitogen-activated protein kinase.

Science.gov (United States)

Lu, D; Yang, H; Raizada, M K

1996-12-01

Angiotensin II (Ang II) stimulates expression of tyrosine hydroxylase and norepinephrine transporter genes in brain neurons; however, the signal-transduction mechanism is not clearly defined. This study was conducted to determine the involvement of the mitogen-activated protein (MAP) kinase signaling pathway in Ang II stimulation of these genes. MAP kinase was localized in the perinuclear region of the neuronal soma. Ang II caused activation of MAP kinase and its subsequent translocation from the cytoplasmic to nuclear compartment, both effects being mediated by AT1 receptor subtype. Ang II also stimulated SRE- and AP1-binding activities and fos gene expression and its translocation in a MAP kinase-dependent process. These observations are the first demonstration of a downstream signaling pathway involving MAP kinase in Ang II-mediated neuromodulation in noradrenergic neurons.

Temperature prediction in high speed bone grinding using motor PWM signal.

Science.gov (United States)

Tai, Bruce L; Zhang, Lihui; Wang, Anthony C; Sullivan, Stephen; Wang, Guangjun; Shih, Albert J

2013-10-01

This research explores the feasibility of using motor electrical feedback to estimate temperature rise during a surgical bone grinding procedure. High-speed bone grinding is often used during skull base neurosurgery to remove cranial bone and approach skull base tumors through the nasal corridor. Grinding-induced heat could propagate and potentially injure surrounding nerves and arteries, and therefore, predicting the temperature in the grinding region would benefit neurosurgeons during the operation. High-speed electric motors are controlled by pulse-width-modulation (PWM) to alter the current input and thus maintain the rotational speed. Assuming full mechanical to thermal power conversion in the grinding process, PWM can be used as feedback for heat generation and temperature prediction. In this study, the conversion model was established from experiments under a variety of grinding conditions and an inverse heat transfer method to determine heat flux. Given a constant rotational speed, the heat conversion was represented by a linear function, and could predict temperature from the experimental data with less than 20% errors. Such results support the advance of this technology for practical application. Copyright © 2013 IPEM. Published by Elsevier Ltd. All rights reserved.

A novel five-level optimized carrier multilevel PWM quad-inverter six-phase AC drive

DEFF Research Database (Denmark)

Sanjeevikumar, P.; Blaabjerg, F.; Wheeler, Pat

2016-01-01

A novel single carrier pulse-width modulation (PWM) for a new quad-inverter configuration for multilevel six-phase asymmetrical open-winding ac converter is proposed in this article. Modularity of the circuit consist of four standard two-level voltage source inverters (VSIs) with slight modificat......A novel single carrier pulse-width modulation (PWM) for a new quad-inverter configuration for multilevel six-phase asymmetrical open-winding ac converter is proposed in this article. Modularity of the circuit consist of four standard two-level voltage source inverters (VSIs) with slight...... modifications, i.e. one additional bi-direction switch (MOSFET/IGBT) in each phase and a link to neutral with two capacitors to generate increased output levels. Furthermore, original optimal single carrier zero-shifted five-level modulation (SCZSFM) algorithm is developed for each VSI to behave as equivalent...

A High-Precision Control for a ZVT PWM Soft-Switching Inverter to Eliminate the Dead-Time Effect

Directory of Open Access Journals (Sweden)

Baoquan Kou

2016-07-01

Full Text Available Attributing to the advantages of high efficiency, low electromagnetic interference (EMI noise and closest to the pulse-width-modulation (PWM converter counterpart, zero-voltage-transition (ZVT PWM soft-switching inverters are very suitable for high-performance applications. However, the conventional control algorithms intended for high efficiency generally results in voltage distortion. Thus, this paper, for the first time, proposes a high-precision control method to eliminate the dead-time effect through controlling the auxiliary current in the auxiliary resonant snubber inverter (ARSI, which is a typical ZVT PWM inverter. The dead-time effect of ARSI is analyzed, which is distinguished from hard-switching inverters. The proposed high-precision control is introduced based on the investigation of dead-time effect. A prototype was developed to verify the effectiveness of the proposed control. The experimental results shows that the total harmonic distortion (THD of the output current of the ARSI can be reduced compared with that of the hard-switching inverter, because the blanking delay error is eliminated. The quality of the output current and voltage can be further improved by utilizing the proposed control method.

Resveratrol inhibits PDGF receptor mitogenic signaling in mesangial cells: role of PTP1B

Science.gov (United States)

Venkatesan, Balachandar; Ghosh-Choudhury, Nandini; Das, Falguni; Mahimainathan, Lenin; Kamat, Amrita; Kasinath, Balakuntalam S.; Abboud, Hanna E.; Choudhury, Goutam Ghosh

2008-01-01

Mesangioproliferative glomerulonephritis is associated with overactive PDGF receptor signal transduction. We show that the phytoalexin resveratrol dose dependently inhibits PDGF-induced DNA synthesis in mesangial cells with an IC50 of 10 μM without inducing apoptosis. Remarkably, the increased SIRT1 deacetylase activity induced by resveratrol was not necessary for this inhibitory effect. Resveratrol significantly blocked PDGF-stimulated c-Src and Akt kinase activation, resulting in reduced cyclin D1 expression and attenuated pRb phosphorylation and cyclin-dependent kinase-2 (CDK2) activity. Furthermore, resveratrol inhibited PDGFR phosphorylation at the PI 3 kinase and Grb-2 binding sites tyrosine-751 and tyrosine-716, respectively. This deficiency in PDGFR phosphorylation resulted in significant inhibition of PI 3 kinase and Erk1/2 MAPK activity. Interestingly, resveratrol increased the activity of protein tyrosine phosphatase PTP1B, which dephosphorylates PDGF-stimulated phosphorylation at tyrosine-751 and tyrosine-716 on PDGFR with concomitant reduction in Akt and Erk1/2 kinase activity. PTP1B significantly inhibited PDGF-induced DNA synthesis without inducing apoptosis. These results for the first time provide evidence that the stilbene resveratrol targets PTP1B to inhibit PDGFR mitogenic signaling.—Venkatesan, B., Ghosh-Choudhury, N., Das, F., Mahimainathan, L., Kamat, A., Kasinath, B. S., Abboud, H. E., Choudhury, G. G. Resveratrol inhibits PDGF receptor mitogenic signaling in mesangial cells: role of PTP1B. PMID:18567737

Comparison of two different techniques on the human lymphocytes morphology and sensitivity to gamma radiation

International Nuclear Information System (INIS)

Kol, R.

1985-02-01

The lymphocytes in the peripheral blood are divided into two main subclasses: T cells and B cells. These differ from each other in function and in their sensitivity to radiation. The effort to study which group is more sensitive to radiation has resulted in many contradictory results. In the present study we examined whether the methods that are used to separate the lymphocytes from the whole blood, before their separation into subclasses, have an effect on the cells and whether this might contribute to the contradictory results. Blood samples were taken from several normal donors and each sample was devided into two fractions. Lymphocytes in each fraction were separated by one of the two following methods: a) sedimentation of erythrocytes by gravitation; b) separation on Ficoll-Paque density gradient. For cells obtained by these two methods, the ultrastructure was examined by electron microscopy and their ability to incorporate radioactive thymidine was measured. Samples separated on Ficoll-Paque showed a subpopulation with morphological changes similar to those occuring in lymphocytes undergoing stimulation. Unstimulated cells separated on Ficoll-Paque showed greater sensitivity to radiation. The effect of gamma radiation on the capability of lymphocytes to undergo transformation in response to three mitogens; PHA, PWM and Con A was examined. Different mitogens stimulate different lymphocytes subpopulations. There was no difference between the two separation methods regarding the sensitivity to gamma radiation of stimulation by PAH and PWM. The transformation by Con A of lymphocytes separated on Ficoll-Paque was more radiosensitive. This could indicate that the separation by Ficoll-Paque density gradient causes a selective depletion of T lymphocytes that react with Con A and are considered more radioresistant. The use of different methods for separating lymphocytes from whole blood- each has a different influence on the cells- can contribute to contradictory

Tipe Dry Cell dan Wet Cell berdimensi 80 x 80 mm dengan Penambahan PWM E-3 FF (1 kHz

Directory of Open Access Journals (Sweden)

Yanur Arzaqa Ghiffari

2013-09-01

Full Text Available Ketersediaan bahan bakar minyak semakin terbatas dan hasil pembakarannya berdampak pada pencemaran lingkungan, salah satu solusinya dengan memanfaatkan gas HHO pada kendaraan bermotor. Penelitian dengan sistem direct connection, temperatur mencapai lebih dari 90oC menyebabkan  generator HHO menjadi rusak dan meleleh, maka penelitian ini menambahan alat untuk mengkontrol besarnya arus, frekuensi, dan duty cycle. Pengembangan generator HHO menggunakan tipe kering (dry cell dan tipe basah (wet cell dengan penambahan PWM (Pulse Width Modulation E-3 Fixed Frequency 1 kHz divariasikan berupa duty cycle: 20%, 40%, 60%, 80%  dan direct connection. Pengujian dilakukan di Laboratorium Teknik Pembakaran dan Bahan Bakar - Teknik Mesin ITS.  Dari hasil penelitian didapatkan karakteristik unjuk kerja terbaik pada kedua tipe generator HHO dengan penambahan PWM. Nilai arus dan tegangan lebih stabil dibandingkan dengan tanpa penambahan PWM (direct connection, namun arus cenderung meningkat seiring dengan kenaikan temperatur mencapai 70oC. Efisiensi terbaik pada generator tipe wet dengan duty cycle 80%,  yaitu 27,7 %.

A PWM Controller of a Full Bridge Single-Phase Synchronous Inverter for Micro-Grid System

Science.gov (United States)

Rahman, Tawfikur; Motakabber, S. M. A.; Ibrahimy, M. I.; Raghib, Aliza ‘Aini Binti Md Ralib@ Md

2017-12-01

Nowadays, microgrid system technology is becoming popular for small area power management systems. It is essential to be less harmonic-distortion and high efficiency of the inverter for microgrid applications. Pulse width modulation (PWM) controller is a conventional switching control technique which is suitable to use in the microgrid connected power inverter system. The control method and algorithm of this technique are challenging, and different approaches are required to avoid the complexity for a customized solution of the microgrid application. This paper proposes a comparative analysis of different controller and their operational methods. A PWM controller is used to reduce the ripple voltage noise while a continuous current mode provides a small output ripple which gives steady-state error as zero on fundamental and cutoff frequency. To reduce the ripple current, higher frequency harmonic distortion, switching loss and phase noise, LC low pass filter is used on either side of input and output terminals. The proposed inverter is designed by MATLAB 2016a simulation software. A balanced load resistance (RL = 20.5 Ω) of star configuration and a dual input DC voltage of ± 35V are considered. In this design, the circuit parameters, the fundamental frequency of 50 Hz, the PWM duty cycle of 95%, the cutoff frequency of the switching controller of 33 kHz are considered. The inverter in this paper exhibits THD of 0.44% and overall efficiency approximately of 98%. The proposed inverter is expected to be suitable for microgrid applications.

Highly Sensitive Temperature Sensors Based on Fiber-Optic PWM and Capacitance Variation Using Thermochromic Sensing Membrane

Directory of Open Access Journals (Sweden)

Md. Rajibur Rahaman Khan

2016-07-01

Full Text Available In this paper, we propose a temperature/thermal sensor that contains a Rhodamine-B sensing membrane. We applied two different sensing methods, namely, fiber-optic pulse width modulation (PWM and an interdigitated capacitor (IDC-based temperature sensor to measure the temperature from 5 °C to 100 °C. To the best of our knowledge, the fiber-optic PWM-based temperature sensor is reported for the first time in this study. The proposed fiber-optic PWM temperature sensor has good sensing ability; its sensitivity is ~3.733 mV/°C. The designed temperature-sensing system offers stable sensing responses over a wide dynamic range, good reproducibility properties with a relative standard deviation (RSD of ~0.021, and the capacity for a linear sensing response with a correlation coefficient of R2 ≈ 0.992 over a wide sensing range. In our study, we also developed an IDC temperature sensor that is based on the capacitance variation principle as the IDC sensing element is heated. We compared the performance of the proposed temperature-sensing systems with different fiber-optic temperature sensors (which are based on the fiber-optic wavelength shift method, the long grating fiber-optic Sagnac loop, and probe type fiber-optics in terms of sensitivity, dynamic range, and linearity. We observed that the proposed sensing systems have better sensing performance than the above-mentioned sensing system.

Active and reactive power control of a current-source PWM-rectifier using space vectors

Energy Technology Data Exchange (ETDEWEB)

Salo, M.; Tuusa, H. [Tampere University of Technology (Finland). Department of Electrical Engineering, Power Electronics

1997-12-31

In this paper the current-source PWM-rectifier with active and reactive power control is presented. The control system is realized using space vector methods. Also, compensation of the reactive power drawn by the line filter is discussed. Some simulation results are shown. (orig.) 8 refs.

Improving dynamic performances of PWM-driven servo-pneumatic systems via a novel pneumatic circuit.

Science.gov (United States)

Taghizadeh, Mostafa; Ghaffari, Ali; Najafi, Farid

2009-10-01

In this paper, the effect of pneumatic circuit design on the input-output behavior of PWM-driven servo-pneumatic systems is investigated and their control performances are improved using linear controllers instead of complex and costly nonlinear ones. Generally, servo-pneumatic systems are well known for their nonlinear behavior. However, PWM-driven servo-pneumatic systems have the advantage of flexibility in the design of pneumatic circuits which affects the input-output linearity of the whole system. A simple pneumatic circuit with only one fast switching valve is designed which leads to a quasi-linear input-output relation. The quasi-linear behavior of the proposed circuit is verified both experimentally and by simulations. Closed loop position control experiments are then carried out using linear P- and PD-controllers. Since the output position is noisy and cannot be directly differentiated, a Kalman filter is designed to estimate the velocity of the cylinder. Highly improved tracking performances are obtained using these linear controllers, compared to previous works with nonlinear controllers.

Phosphorylation and activation of p42 and p44 mitogen-activated protein kinase are required for the P2 purinoceptor stimulation of endothelial prostacyclin production.

Science.gov (United States)

Patel, V; Brown, C; Goodwin, A; Wilkie, N; Boarder, M R

1996-11-15

Extracellular ATP and ADP, released from platelets and other sites stimulate the endothelial production of prostacyclin (PGI2) by acting on G-protein-coupled P2Y2 and P2Y2 purinoceptors, contributing to the maintenance of a non-thrombogenic surface. The mechanism, widely described as being dependent on elevated cytosolic [Ca2+], also requires protein tyrosine phosphorylation. Here we show that activation of both these P2 receptor types leads to the tyrosine phosphorylation and activation of both the p42 and p44 forms of mitogen-activated protein kinase (MAPK). 2-Methylthio-ATP and UTP, selectively activating P2Y1 and P2Y2 purinoceptors respectively, and ATP, a non-selective agonist at these two receptors, stimulate the tyrosine phosphorylation of both p42mapk and p44mapk, as revealed by Western blots with an antiserum specific for the tyrosine-phosphorylated forms of the enzymes. By using separation on Resource Q columns, peptide kinase activity associated with the phosphorylated MAPK enzymes distributes into two peaks, one mainly p42mapk and one mainly p44mapk, both of which are stimulated by ATP with respect to kinase activity and phospho-MAPK immunoreactivity. Stimulation of P2Y1 or P2Y2 purinoceptors leads to a severalfold increase in PGI2 efflux; this was blocked in a dose-dependent manner by the selective MAPK kinase inhibitor PD98059. This drug also blocked the agonist-stimulated increase in phospho-MAPK immunoreactivity for both p42mapk and p44mapk but left the phospholipase C response to P2 agonists essentially unchanged. Olomoucine has been reported to inhibit p44mapk activity. Here we show that in the same concentration range olomoucine inhibits activity in both peaks from the Resource Q column and also the agonist stimulation of 6-keto-PGF1, but has no effect on agonist-stimulated phospho-MAPK immunoreactivity. These results provide direct evidence for the involvement of p42 and p44 MAPK in the PGI2 response of intact endothelial cells: we have shown

Common variable immunodeficiency in a horse.

Science.gov (United States)

Flaminio, M Julia B F; LaCombe, Veronique; Kohn, Catherine W; Antczak, Douglas F

2002-11-01

A 12-year-old Quarter Horse mare that was nonresponsive to medical treatment was evaluated for chronic respiratory disease and hepatobiliary disease. Serum immunoglobulin concentrations were measured by use of radial immunodiffusion that revealed trace to nondetectable concentrations of IgG, IgG(T), IgM, and IgA. Use of serum protein electrophoresis confirmed agammaglobulinemia by the absence of the expected peak in the gamma region. In addition, vaccination with tetanus toxoid did not result in specific immunoglobulin production. Flow cytometric analysis of blood lymphocyte subpopulations revealed the absence of B cells in blood. Immunohistochemical analysis of tissue sections revealed the absence of B lymphocytes in bone marrow and spleen, with occasional B cells in the peripheral lymph nodes. Blood lymphocyte proliferation assays revealed weak responses to pokeweed mitogen and no response to stimulation with lipopolysaccharide. Considering the age and sex of the horse, results of the immunologic tests suggested a diagnosis of common variable immunodeficiency.

Electromagnetic phenomena analysis in brushless DC motor with speed control using PWM method

Science.gov (United States)

Ciurys, Marek Pawel

2017-12-01

Field-circuit model of a brushless DC motor with speed control using PWM method was developed. Waveforms of electrical and mechanical quantities of the designed motor with a high pressure vane pump built in a rotor of the motor were computed. Analysis of electromagnetic phenomena in the system: single phase AC network - converter - BLDC motor was carried out.

Immunological studies in acquired immunodeficiency syndrome. Functional studies of lymphocyte subpopulations

DEFF Research Database (Denmark)

Hofmann, B; Ødum, Niels; Platz, P

1985-01-01

The lymphocyte transformation response in vitro to mitogens (phytohaemagglutinin, concanavalin A, and pokeweed mitogen) and antigens (purified protein derivative and tetanus) was studied in three patients with acquired immunodeficiency syndrome (AIDS), three patients with pre-AIDS, and six healthy...... controls before and after depletion of T4- or T8-positive cells. In controls, T8-depleted lymphocytes responded as well as peripheral blood mononuclear cells (PBMC) when monocytes were added, whereas T4-depleted cells gave about 50% of this response to mitogens and no response at all to antigens....... No evidence of suppression was seen when various mixtures of T4- and T8-depleted cells were made. In particular, there was a virtually linear relationship between the percentage of T8-depleted cells and the response to antigens. The PBMC of all AIDS and pre-AIDS patients had very low or absent responses...

Design of a High Performance Green-Mode PWM Controller IC with Smart Sensing Protection Circuits

Directory of Open Access Journals (Sweden)

Shen-Li Chen

2014-08-01

Full Text Available A design of high performance green-mode pulse-width-modulation (PWM controller IC with smart sensing protection circuits for the application of lithium-ion battery charger (1.52 V ~ 7.5 V is investigated in this paper. The protection circuits architecture of this system mainly bases on the lithium battery function and does for the system design standard of control circuit. In this work, the PWM controller will be with an automatic load sensing and judges the system operated in the operating mode or in the standby mode. Therefore, it reduces system’s power dissipation effectively and achieves the saving power target. In the same time, many protection sensing circuits such as: (1 over current protection (OCP and under current protection (UCP, (2 over voltage protection (OVP and under voltage protection (UVP, (3 loading determintion and short circuit protection (SCP, (4 over temperature protection (OTP, (5 VDD surge-spiking protection are included. Then, it has the characteristics of an effective monitoring the output loading and the harm prevention as a battery charging. Eventually, this green-mode pulse-width-modulation (PWM controller IC will be that the operation voltage is 3.3 V, the operation frequency is 0.98 MHz, and the output current range is from 454 mA to 500 mA. Meanwhile, the output convert efficiency is range from 74.8 % to 91 %, the power dissipation efficiency in green-mode is 25 %, and the operation temperature range is between -20 0C ~ 114 0C.

New PWM method and commutation strategy for HF-link converters for fuel cells and photovoltaics

DEFF Research Database (Denmark)

Ljusev, Petar; Andersen, Michael Andreas E.

2005-01-01

This paper presents a new PWM method and commutation strategy for HF-link converters, which leads to safe commutation of the load current in the output bidirectional bridge. The proposed implementation is independent of the particular HF-link converter topology and bidirectional switch selection ...

Effect of metallurgical factors on the magnetic properties of non-oriented electrical steels under PWM excitation

International Nuclear Information System (INIS)

Tanaka, T.; Yashiki, H.; Takada, S.; Sasaki, T.

1994-01-01

Magnetic properties of non-oriented electrical steel sheets under PWM voltage excitation as well as those under sinusoidal excitation have been investigated from a metallurgical point of view. The core loss under PWM excitation is slightly larger than that under sinusoidal excitation. The induction dependence of the core loss difference between the two excitation conditions changes by changing Si content and grain size. The higher the induction, the larger the core loss difference of 0.2% Si steel with small grains. In the case of higher Si steels and 0.2% Si steel with large grain sizes, however, the core loss difference at inductions over 1.3 T decreases with increasing induction. At low induction levels the core loss difference has little relationship to the grain size. On the other hand, at high induction levels this difference decreases with increasing grain size. ((orig.))

Six-Phase Vehicular Drive with Renewable DC Sources and Hybrid PWM Control of Four Inverters

DEFF Research Database (Denmark)

Oleschuk, Valentin; Ermuratskii, Vladimir; Blaabjerg, Frede

2015-01-01

The paper presents results of research of quad-inverter-based automotive system with combined scheme of PWM control of inverters, supplied by two renewable dc sources (by fuel cells and by battery). It has been shown, that hybrid switching techniques can be used successfully for control of vehicle...

Self oscillating PWM modulators, a topological comparison

DEFF Research Database (Denmark)

Poulsen, Søren; Andersen, Michael Andreas E.

2004-01-01

or fs/ð range respectively, where fs is the switching frequency of the converter. For some applications this will require unacceptable high switching frequency to achieve enough control loop bandwidth for the desired dynamic performance. With self oscillating modulators, the open loop bandwidth is equal...... to fs which makes this type of modulators an excellent choice for a wide range of applications. Self oscillating PWM modulators can be made in a number of ways, either as voltage or current mode modulators, and the self oscillating behavior can be achieved either by using hysteresis control...... or by shaping the open loop function of the modulator so its gain and phase response causes a closed loop natural oscillation. The two main types of self oscillating modulators have many similarities, but differences in dynamic performance and linearity are present. The work presented is related to the author...

A ZVS PWM control strategy with balanced capacitor current for half-bridge three-level DC/DC converter

DEFF Research Database (Denmark)

Liu, Dong; Deng, Fujin; Chen, Zhe

2017-01-01

The capacitor current would be imbalanced under the conventional control strategy in the half-bridge three-level (HBTL) DC/DC converter due to the effect of the output inductance of the power supply and the input line inductance, which would affect the converter's reliability. This paper proposes...... a pulse-wide modulation (PWM) strategy composed of two operation modes for the HBTL DC/DC converter, which can realize the zero-voltage switching (ZVS) for the efficiency improvement. In addition, a capacitor current balancing control is proposed by alternating the two operation modes of the proposed ZVS...... PWM strategy, which can eliminate the current imbalance among the two input capacitors. Therefore, the proposed control strategy can improve the converter's performance and reliability in: 1) reducing the switching losses and noises of the power switches; 2) balancing the thermal stresses...

Modelling and Controller Design of Electro-Pneumatic Actuator Based on PWM

Directory of Open Access Journals (Sweden)

Behrouz Najjari

2012-07-01

Full Text Available In this paper, a nonlinear model associated to the fast switching on-off solenoid valve and pneumatic cylinder was dynamically presented. Furthermore, an investigation into the electrical, magnetic, mechanical and fluid subsystems are made. Two common control policies to track valve position, a Proportional Integrator (PI based on Pulse Width Modulation (PWM and hysteresis controllers, are investigated. To control cylinder position, a Programmable Logic Controller (PLC on a simulated unit and an experimental setup regulated with AVR microcontroller are carried out. Experimental results show effective validation to the simulation results from PLC.

Stimulation of aortic smooth muscle cell mitogenesis by serotonin

International Nuclear Information System (INIS)

Nemecek, G.M.; Coughlin, S.R.; Handley, D.A.; Moskowitz, M.A.

1986-01-01

Bovine aortic smooth muscle cells in vitro responded to 1 nM to 10 μM serotonin with increased incorporation of [ 3 H]thymidine into DNA. The mitogenic effect of serotonin was half-maximal at 80 nM and maximal above 1 μM. At a concentration of 1 μM, serotonin stimulated smooth muscle cell mitogenesis to the same extent as human platelet-derived growth factor (PDGF) at 12 ng/ml. Tryptamine was ≅ 1/10th as potent as serotonin as a mitogen for smooth muscle cells. Other indoles that are structurally related to serotonin (D- and L-tryptophan, 5-hydroxy-L-tryptophan, N-acetyl-5-hydroxytryptamine, melatonin, 5-hydroxyindoleacetic acid, and 5-hydroxytryptophol) and quipazine were inactive. The stimulatory effect of serotonin on smooth muscle cell DNA synthesis required prolonged (20-24 hr) exposure to the agonist and was attenuated in the presence of serotonin D receptor antagonists. When smooth muscle cells were incubated with submaximal concentrations of serotonin and PDGF, synergistic rather than additive mitogenic responses were observed. These data indicate that serotonin has a significant mitogenic effect on smooth muscle cells in vitro, which appears to be mediated by specific plasma membrane receptors

T-lymphocyte dependency of B-lymphocyte blastogenic response to phytomitogens

International Nuclear Information System (INIS)

Han, T.; Dadey, B.

1978-01-01

Human peripheral blood T and B lymphocytes were separated by a method based on the stable rosette formation of T lymphocytes with neuraminidase-treated sheep erythrocytes, followed by centrifugation over a Ficoll-Hypaque gradient. Monocytes were isolated from the T-depleted B lymphocyte preparation by allowing the monocytes to ingest iron particles and by subsequent centrifugation over a Ficoll-Hypaque gradient. The T lymphocytes responded extremely well to PHA and very well to PWM, while the B lymphocytes were unresponsive to either PHA or PWM. However, when the B lymphocytes were cultured together with irradiated autologous or allogeneic T lymphocytes (1 : 1,1:2 or 1 : 4 ratio), both PHA and PWM became mitogenic to B lymphocytes. Irradiated T lymphocytes alone did not respond to either PHA or PWM, indicating that the 3 H-thymidine incorporation seen in the mixed-cell culture was due to the activation of unirradiated B lymphocytes. The B lymphocytes failed to respond to these phytomitogens in the presence of lower concentrations of irradiated T lymphocytes. The monocytes were found to be incapable of helping the B lymphocytes to respond to PHA or PWM. (author)

Transformer-assisted PWM zero-voltage switching pole inverter with high output bandwidth applied to linear motor drives

NARCIS (Netherlands)

Myrzik, J.M.A.; Duarte, J.L.; Haardt, de P.; Vissers, J.

2002-01-01

An application of the transformer-assisted PWM zero-voltage switching pole inverter (TRAP) is described in this paper. The TRAP is based on the auxiliary resonant commutated pole inverter (ARCP), but avoids its disadvantages. This paper describes the converter functionality and its applicability

Dynamic Sliding Mode Evolution PWM Controller for a Novel High-Gain Interleaved DC-DC Converter in PV System

Directory of Open Access Journals (Sweden)

Taizhou Bei

2014-01-01

Full Text Available Considering the disadvantages of the traditional high-gain DC-DC converter such as big size, high voltage stress of switches, and large input current ripple, a novel high-gain interleaved boost converter with coupled-inductor and switched-capacitor was proposed correspondingly and the operation principle together with the steady-state analysis of this converter was also described. Besides, a new control approach-dynamic sliding mode evolution PWM controller (DSME PWM for the novel topological converter based on both dynamic evolution and sliding mode control was also presented. From the simulation results and experimental validation the proposed converter can fulfill high-gain boost, low ripple of both the input current and the output voltage. Furthermore, MPPT technique can be also achieved in a short time by simulation. The efficiency and stability of the converter proposed in this paper can be improved.

A Harmonic Resonance Suppression Strategy for a High-Speed Railway Traction Power Supply System with a SHE-PWM Four-Quadrant Converter Based on Active-Set Secondary Optimization

Directory of Open Access Journals (Sweden)

Runze Zhang

2017-10-01

Full Text Available Pulse width modulation (PWM technology is widely used in traction converters for high-speed railways. The harmonic distribution caused by PWM is quite extensive, and increases the possibility of grid–train coupling resonance in the traction power supply system (TPSS. This paper first analyzes the mechanism of resonance, when the characteristic harmonic frequency of a four-quadrant converter (4QC current that injects into the traction grid matches the resonant frequency of the traction grid, which may result in resonance in the system. To suppress resonance, this paper adopts specific harmonic elimination–pulse width modulation (SHE-PWM technology combined with a transient direct current control strategy to eliminate the harmonics in the resonant frequency, which may suppress the grid–train coupling resonance. Due to the fact that the SHE-PWM process with multiple switching angles contains complex transcendental equations, the initial value is difficult to provide, and is difficult to solve using ordinary iterative algorithms. In this paper, an active-set secondary optimization method is used to solve the equation. The algorithm has the benefits of low dependence on initial values, fast convergence and high solution accuracy. Finally, the feasibility of the resonant suppression algorithm is verified by means of Matlab simulation.

Soft switching PWM isolated boost converter for fuel cell application

Energy Technology Data Exchange (ETDEWEB)

Rezaei, M.; Adib, E. [Isfahan Univ. of Technology, Isfahan (Iran, Islamic Republic of)

2009-07-01

This presentation introduced a newly developed soft switching, isolated boost type converter for fuel cell applications. With a simple PWM control circuit, the converter achieves zero voltage switching the main switch. Since the auxiliary circuit is soft switched, the converter can operate at high powers which make it suitable for fuel cell applications. In particular, the converter is suitable for the interface of fuel cell and inverters because of its high voltage gain and isolation between input and output sources. In addition, the input current of the converter (current drained from the fuel cell) is almost constant since it is a boost type converter. The converter was analyzed and the simulation results validate the theoretical analysis.

A new PWM algorithm for battery-source three-phase inverters

Energy Technology Data Exchange (ETDEWEB)

Chan, C.C. (Dept. of Electrical and Electronic Engineering, Univ. of Hong Kong, Pokfulam Road (HK)); Chau, K.T. (Dept. of Electrical Engineering, Hong Kong Polytechnic, Hung Hom (HK))

1991-01-01

A new PWM algorithm for battery-source three-phase inverters is described in this paper. The concept of the algorithm is to determine the pulsewidths by equating the areas of the segments of the sinusodial reference with the related output pulse areas. The algorithm is particularly suitable to handle a non-constant voltage source with good harmonic suppression. Since the pulsewidths are computable in real time with minimal storage requirement as well as compact hardware and software, it is especially suitable for single-chip microcomputer implementation. Experimental results show that the single-chip microcomputer Intel 8095-based battery-source inverter can control a 3 kW synchronous motor drive satisfactorily over a frequency range of 2 to 100Hz.

CNS activity of Pokeweed Anti-viral Protein (PAP in mice infected with Lymphocytic Choriomeningitis Virus (LCMV

Directory of Open Access Journals (Sweden)

Tibbles Heather E

2005-02-01

Full Text Available Abstract Background Others and we have previously described the potent in vivo and in vitro activity of the broad-spectrum antiviral agent PAP (Pokeweed antiviral protein against a wide range of viruses. The purpose of the present study was to further elucidate the anti-viral spectrum of PAP by examining its effects on the survival of mice challenged with lymphocytic choriomeningitis virus (LCMV. Methods We examined the therapeutic effect of PAP in CBA mice inoculated with intracerebral injections of the WE54 strain of LCMV at a 1000 PFU dose level that is lethal to 100% of mice within 7–9 days. Mice were treated either with vehicle or PAP administered intraperitoneally 24 hours prior to, 1 hour prior to and 24 hours, 48 hours 72 hours and 96 hours after virus inoculation. Results PAP exhibits significant in vivo anti- LCMV activity in mice challenged intracerebrally with an otherwise invariably fatal dose of LCMV. At non-toxic dose levels, PAP significantly prolonged survival in the absence of the majority of disease-associated symptoms. The median survival time of PAP-treated mice was >21 days as opposed to 7 days median survival for the control (p = 0.0069. Conclusion Our results presented herein provide unprecedented experimental evidence that PAP exhibits antiviral activity in the CNS of LCMV-infected mice.

Power system stabilization by SMES using current-fed pwm power conditioner

International Nuclear Information System (INIS)

Ishikawa, T.; Akita, S.; Taniguchi, H.; Kosho, S.; Tanaka, T.

1988-01-01

A superconducting magnetic energy storage (SMES) unit, consisted of superconducting coil and AC/DC power conditioner, can be used to suppress various kinds of instability that may cause service interruption in electric power system as it has high controllability of input/output electric power. Power system stabilizing ability of SMES has been examined experimentally by using model power system and small SMES unit. Current-fed PWM power conditioner was used to obtain maximum stabilizing effect by controlling active and reactive power simultaneously and independently. Power conditioner configuration, operating characteristics and control scheme for power system stabilization are also described. Results from experiments show the effectiveness of SMES on power system stabilization

Zero-Voltage Switching PWM Strategy Based Capacitor Current-Balancing Control for Half-Bridge Three-Level DC/DC Converter

DEFF Research Database (Denmark)

Liu, Dong; Deng, Fujin; Zhang, Qi

2018-01-01

The current imbalance among the two input capacitors is one of the important issues of the half-bridge threelevel (HBTL) DC/DC converter, which would affect system performance and reliability. In this paper, a zero-voltage switching (ZVS) pulse-wide modulation (PWM) strategy including two operation...

Nicotine stimulates urokinase-type plasminogen activator receptor expression and cell invasiveness through mitogen-activated protein kinase and reactive oxygen species signaling in ECV304 endothelial cells

Energy Technology Data Exchange (ETDEWEB)

Khoi, Pham Ngoc; Park, Jung Sun; Kim, Nam Ho; Jung, Young Do, E-mail: ydjung@chonnam.ac.kr

2012-03-01

Urokinase-type plasminogen activator receptor (uPAR) expression is elevated during inflammation, tissue remodeling and in many human cancers. This study investigated the effect of nicotine, a major alkaloid in tobacco, on uPAR expression and cell invasiveness in ECV304 endothelial cells. Nicotine stimulated uPAR expression in a dose-dependent manner and activated extracellular signal-regulated kinases-1/2 (Erk-1/2), c-Jun amino-terminal kinase (JNK) and p38 mitogen activated protein kinase (MAPK). Specific inhibitors of MEK-1 (PD98059) and JNK (SP600125) inhibited the nicotine-induced uPAR expression, while the p38 MAPK inhibitor SB203580 did not. Expression vectors encoding dominant negative MEK-1 (pMCL-K97M) and JNK (TAM67) also prevented nicotine-induced uPAR promoter activity. The intracellular hydrogen peroxide (H{sub 2}O{sub 2}) content was increased by nicotine treatment. The antioxidant N-acetylcysteine prevented nicotine-activated production of reactive oxygen species (ROS) and uPAR expression. Furthermore, exogenous H{sub 2}O{sub 2} increased uPAR mRNA expression. Deleted and site-directed mutagenesis demonstrated the involvement of the binding sites of transcription factor nuclear factor-kappaB (NF-κB) and activator protein (AP)-1 in the nicotine-induced uPAR expression. Studies with expression vectors encoding mutated NF-κB signaling molecules and AP-1 decoy confirmed that NF-κB and AP-1 were essential for the nicotine-stimulated uPAR expression. MAPK (Erk-1/2 and JNK) and ROS functioned as upstream signaling molecules in the activation of AP-1 and NF-κB, respectively. In addition, ECV304 endothelial cells treated with nicotine displayed markedly enhanced invasiveness, which was partially abrogated by uPAR neutralizing antibodies. The data indicate that nicotine induces uPAR expression via the MAPK/AP-1 and ROS/NF-κB signaling pathways and, in turn, stimulates invasiveness in human ECV304 endothelial cells. -- Highlights: ► Endothelial cells

Nicotine stimulates urokinase-type plasminogen activator receptor expression and cell invasiveness through mitogen-activated protein kinase and reactive oxygen species signaling in ECV304 endothelial cells

International Nuclear Information System (INIS)

Khoi, Pham Ngoc; Park, Jung Sun; Kim, Nam Ho; Jung, Young Do

2012-01-01

Urokinase-type plasminogen activator receptor (uPAR) expression is elevated during inflammation, tissue remodeling and in many human cancers. This study investigated the effect of nicotine, a major alkaloid in tobacco, on uPAR expression and cell invasiveness in ECV304 endothelial cells. Nicotine stimulated uPAR expression in a dose-dependent manner and activated extracellular signal-regulated kinases-1/2 (Erk-1/2), c-Jun amino-terminal kinase (JNK) and p38 mitogen activated protein kinase (MAPK). Specific inhibitors of MEK-1 (PD98059) and JNK (SP600125) inhibited the nicotine-induced uPAR expression, while the p38 MAPK inhibitor SB203580 did not. Expression vectors encoding dominant negative MEK-1 (pMCL-K97M) and JNK (TAM67) also prevented nicotine-induced uPAR promoter activity. The intracellular hydrogen peroxide (H 2 O 2 ) content was increased by nicotine treatment. The antioxidant N-acetylcysteine prevented nicotine-activated production of reactive oxygen species (ROS) and uPAR expression. Furthermore, exogenous H 2 O 2 increased uPAR mRNA expression. Deleted and site-directed mutagenesis demonstrated the involvement of the binding sites of transcription factor nuclear factor-kappaB (NF-κB) and activator protein (AP)-1 in the nicotine-induced uPAR expression. Studies with expression vectors encoding mutated NF-κB signaling molecules and AP-1 decoy confirmed that NF-κB and AP-1 were essential for the nicotine-stimulated uPAR expression. MAPK (Erk-1/2 and JNK) and ROS functioned as upstream signaling molecules in the activation of AP-1 and NF-κB, respectively. In addition, ECV304 endothelial cells treated with nicotine displayed markedly enhanced invasiveness, which was partially abrogated by uPAR neutralizing antibodies. The data indicate that nicotine induces uPAR expression via the MAPK/AP-1 and ROS/NF-κB signaling pathways and, in turn, stimulates invasiveness in human ECV304 endothelial cells. -- Highlights: ► Endothelial cells treated with nicotine

Periodic mechanical stress activates EGFR-dependent Rac1 mitogenic signals in rat nucleus pulpous cells via ERK1/2

Energy Technology Data Exchange (ETDEWEB)

Gao, Gongming [Department of Orthopedics, The Affiliated Changzhou No. 2 Hospital of Nanjing Medical University, Changzhou 213003 (China); Shen, Nan [Department of Clinical Pharmacy, The Affiliated Jiangyin Hospital of Southeast University Medical School, Jiangyin 214400 (China); Jiang, Xuefeng; Sun, Huiqing [Department of Orthopedics, The Affiliated Jiangyin Hospital of Southeast University Medical School, Jiangyin 214400 (China); Xu, Nanwei; Zhou, Dong [Department of Orthopedics, The Affiliated Changzhou No. 2 Hospital of Nanjing Medical University, Changzhou 213003 (China); Nong, Luming, E-mail: lumingnong@hotmail.com [Department of Orthopedics, The Affiliated Changzhou No. 2 Hospital of Nanjing Medical University, Changzhou 213003 (China); Ren, Kewei, E-mail: keweiren@hotmail.com [Department of Orthopedics, The Affiliated Jiangyin Hospital of Southeast University Medical School, Jiangyin 214400 (China)

2016-01-15

The mitogenic effects of periodic mechanical stress on nucleus pulpous cells have been studied extensively but the mechanisms whereby nucleus pulpous cells sense and respond to mechanical stimulation remain a matter of debate. We explored this question by performing cell culture experiments in our self-developed periodic stress field and perfusion culture system. Under periodic mechanical stress, rat nucleus pulpous cell proliferation was significantly increased (p < 0.05 for each) and was associated with increases in the phosphorylation and activation of EGFR, Rac1, and ERK1/2 (p < 0.05 for each). Pretreatment with the ERK1/2 selective inhibitor PD98059 reduced periodic mechanical stress-induced nucleus pulpous cell proliferation (p < 0.05 for each), while the activation levels of EGFR and Rac1 were not inhibited. Proliferation and phosphorylation of ERK1/2 were inhibited after pretreatment with the Rac1 inhibitor NSC23766 in nucleus pulpous cells in response to periodic mechanical stress (p < 0.05 for each), while the phosphorylation site of EGFR was not affected. Inhibition of EGFR activity with AG1478 abrogated nucleus pulpous cell proliferation (p < 0.05 for each) and attenuated Rac1 and ERK1/2 activation in nucleus pulpous cells subjected to periodic mechanical stress (p < 0.05 for each). These findings suggest that periodic mechanical stress promotes nucleus pulpous cell proliferation in part through the EGFR-Rac1-ERK1/2 signaling pathway, which links these three important signaling molecules into a mitogenic cascade. - Highlights: • The mechanism involved in nucleus pulpous cells to respond to mechanical stimuli. • Periodic mechanical stress can stimulate the phosphorylation of EGFR. • EGFR activates Rac1 and leads to rat nucleus pulpous cell proliferation. • EGFR and Rac1 activate ERK1/2 mitogenic signals in nucleus pulpous cells. • EGFR-Rac1-ERK1/2 is constitutes at least one critical signal transduction pathway.

Periodic mechanical stress activates EGFR-dependent Rac1 mitogenic signals in rat nucleus pulpous cells via ERK1/2

International Nuclear Information System (INIS)

Gao, Gongming; Shen, Nan; Jiang, Xuefeng; Sun, Huiqing; Xu, Nanwei; Zhou, Dong; Nong, Luming; Ren, Kewei

2016-01-01

The mitogenic effects of periodic mechanical stress on nucleus pulpous cells have been studied extensively but the mechanisms whereby nucleus pulpous cells sense and respond to mechanical stimulation remain a matter of debate. We explored this question by performing cell culture experiments in our self-developed periodic stress field and perfusion culture system. Under periodic mechanical stress, rat nucleus pulpous cell proliferation was significantly increased (p < 0.05 for each) and was associated with increases in the phosphorylation and activation of EGFR, Rac1, and ERK1/2 (p < 0.05 for each). Pretreatment with the ERK1/2 selective inhibitor PD98059 reduced periodic mechanical stress-induced nucleus pulpous cell proliferation (p < 0.05 for each), while the activation levels of EGFR and Rac1 were not inhibited. Proliferation and phosphorylation of ERK1/2 were inhibited after pretreatment with the Rac1 inhibitor NSC23766 in nucleus pulpous cells in response to periodic mechanical stress (p < 0.05 for each), while the phosphorylation site of EGFR was not affected. Inhibition of EGFR activity with AG1478 abrogated nucleus pulpous cell proliferation (p < 0.05 for each) and attenuated Rac1 and ERK1/2 activation in nucleus pulpous cells subjected to periodic mechanical stress (p < 0.05 for each). These findings suggest that periodic mechanical stress promotes nucleus pulpous cell proliferation in part through the EGFR-Rac1-ERK1/2 signaling pathway, which links these three important signaling molecules into a mitogenic cascade. - Highlights: • The mechanism involved in nucleus pulpous cells to respond to mechanical stimuli. • Periodic mechanical stress can stimulate the phosphorylation of EGFR. • EGFR activates Rac1 and leads to rat nucleus pulpous cell proliferation. • EGFR and Rac1 activate ERK1/2 mitogenic signals in nucleus pulpous cells. • EGFR-Rac1-ERK1/2 is constitutes at least one critical signal transduction pathway.

Synchronized Scheme of Continuous Space-Vector PWM with the Real-Time Control Algorithms

DEFF Research Database (Denmark)

Oleschuk, V.; Blaabjerg, Frede

2004-01-01

This paper describes in details the basic peculiarities of a new method of feedforward synchronous pulsewidth modulation (PWM) of three-phase voltage source inverters for adjustable speed ac drives. It is applied to a continuous scheme of voltage space vector modulation. The method is based...... their position inside clock-intervals. In order to provide smooth shock-less pulse-ratio changing and quarter-wave symmetry of the voltage waveforms, special synchronising signals are formed on the boundaries of the 60 clock-intervals. The process of gradual transition from continuous to discontinuous...

Estimating return levels from maxima of non-stationary random sequences using the Generalized PWM method

Directory of Open Access Journals (Sweden)

P. Ribereau

2008-12-01

Full Text Available Since the pioneering work of Landwehr et al. (1979, Hosking et al. (1985 and their collaborators, the Probability Weighted Moments (PWM method has been very popular, simple and efficient to estimate the parameters of the Generalized Extreme Value (GEV distribution when modeling the distribution of maxima (e.g., annual maxima of precipitations in the Identically and Independently Distributed (IID context. When the IID assumption is not satisfied, a flexible alternative, the Maximum Likelihood Estimation (MLE approach offers an elegant way to handle non-stationarities by letting the GEV parameters to be time dependent. Despite its qualities, the MLE applied to the GEV distribution does not always provide accurate return level estimates, especially for small sample sizes or heavy tails. These drawbacks are particularly true in some non-stationary situations. To reduce these negative effects, we propose to extend the PWM method to a more general framework that enables us to model temporal covariates and provide accurate GEV-based return levels. Theoretical properties of our estimators are discussed. Small and moderate sample sizes simulations in a non-stationary context are analyzed and two brief applications to annual maxima of CO₂ and seasonal maxima of cumulated daily precipitations are presented.

Mitogen-activated protein kinases mediate Mycobacterium ...

Indian Academy of Sciences (India)

2012-01-19

Jan 19, 2012 ... CD44, an adhesion molecule, has been reported to be a binding site for ... receptors in mediating mitogen-activated protein kinase activation. ... surface expression and tumour necrosis factor-alpha levels, ... Abbreviations used: Abs, antibodies; ANOVA, analysis of variance; AP-1, activator protein -1; BCG, ...

A comprehensive study and analysis of second order harmonic ripple in DC microgrid feeding single phase PWM inverter loads

DEFF Research Database (Denmark)

Gautam, Aditya R.; Fulwani, Deepak; Guerrero, Josep M.

2016-01-01

The paper presents a detailed analysis of second order harmonic ripple in a DC microgrid. A boost converter feeding PWM inverter load is considered and equivalent circuit is proposed. The effect of the size of input capacitor, output capacitor and inductor of boost converter, on this ripple has...

Optimal Method to Stimulate Cytokine Production and Its Use in Immunotoxicity Assessment

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Huiming Chen

2013-08-01

Full Text Available Activation of lymphocytes can effectively produce a large amount of cytokines. The types of cytokines produced may depend on stimulating reagents and treatments. To find an optimal method to stimulate cytokine production and evaluate its effect on immunotoxicity assessments, the authors analyzed production of IL-2, IL-4, IL-6, IL-10, IL-13, IFN-γ, TNF-α, GM-CSF, RANTES and TGF-β in undiluted rat whole blood culture (incubation for 0, 2, 4, 6, 8 or 10 h with different concentrations of PMA/ionomycin, PHA, Con A, LPS and PWM. We also evaluated the effects of cyclosporin A and azathioprine on cytokine production. The results revealed a rapid increase of IL-2, IFN-γ, TNF-α, RANTES and TGF-β secretion within 6 h after stimulation with 25 ng/mL PMA and 1 μg/mL ionomycin. The inhibition of these cytokine profiles reflected the effects of immunosuppressants on the immune system. Therefore, the results of this is study recommend the detection of cytokine profiles in undiluted whole blood stimulated 6 h with 25 ng/mL PMA and 1 μg/mL ionomycin as a powerful immunotoxicity assessment method.

Atmel Microcontroller Based Soft Switched PWM ZVS Full Bridge DC to DC Converter

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DEEPAK KUMAR NAYAK

2010-12-01

Full Text Available This paper deals with the simulation and implementation of soft switched PWM ZVS full bridge DC to DC converter. The 48V DC is efficiently reduced to 12V DC using a DC to DC converter. This converter has advantages like reduced switching losses, stresses and EMI. Input DC is converted into high frequency AC and it is stepped down to 12V level. Later it is rectified using a full wave rectifier. Laboratory model of microcontroller based DC to DC converter is fabricated and tested. The experimental results are compared with the simulation results.

Mitogen-activated protein kinase phosphatase-1 expression in macrophages is controlled by lymphocytes during macrophage activation.

Science.gov (United States)

Luo, Chong; Yang, Xiqiang; Yao, Lan; Jiang, Liping; Liu, Wei; Li, Xin; Wang, Lijia

2012-01-01

The viewpoints on the control of innate immune cells by the adaptive immune system during sepsis remain controversial. Mitogen-activated protein kinase phosphatase-1 (MKP-1) is essential to the negative control of innate immunity and suppresses the activation of macrophages by inhibiting activated mitogen-activated protein kinase (MAPK). The purpose of the current study was to observe inflammatory response and macrophage activation in mice with severe combined immunodeficiency (SCID) with endotoxemia and to determine the role of MKP-1 in the control of macrophage activation by the adaptive immune system. Endotoxemia was induced in wild-type and SCID mice by an intraperitoneal injection of lipopolysaccharide (LPS), and all of the SCID mice died. SCID mice produced more inflammatory cytokines than BALB/c mice systemically and locally. TNF-α mRNA expression was higher and MKP-1 mRNA expression was lower in peritoneal macrophages (PMa) from SCID mice compared to PMa from wild-type mice after and even before LPS injection. Thioglycollate-stimulated PMa from wild-type mice were stimulated with LPS in vitro in the presence or absence of pan-T cells. The levels of TNF-α and IL-6 were higher in the supernatants from PMa cultured alone compared to PMa co-cultured with pan-T cells, and PMa MKP-1 mRNA and protein expression were higher when PMa were co-cultured with pan-T cells. Therefore, pan-T cells can up-regulate MKP-1 expression in macrophages and inhibit the secretion of inflammatory cytokines secretion by macrophages. In SCID mice, lymphocyte deficiency, especially T cell deficiency, causes insufficient MKP-1 expression in macrophages, which can be responsible for the severe inflammation and bad prognosis of septic SCID mice. MKP-1 plays an important role in the control of macrophage activation by the adaptive immune system.

Thin grain oriented electrical steel for PWM voltages fed magnetic cores

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Thierry Belgrand

2018-04-01

Full Text Available This paper reports on performances of high permeability grain oriented electrical steel when used in association with power electronic switching devices. Loss measurement results obtained from the Epstein test, using sinusoidal or various PWM voltages in medium frequency range, show that for both studied thicknesses (HGO 0.23mm and HGO 0.18mm, comparing performances at a fixed induction level between the various situations may not be the most convenient method. The effect of magnetic domain refinement has been investigated. After having shown the interest of lowering the thickness, an alternative way of looking at losses is proposed that may help to design the magnetic core when it comes to the matter of reducing size in considering frequency and magnetization levels.

A Comparison of Phase-Shift Self- Oscillating and Carrier-based PWM Modulation for Embedded Audio Amplifiers

OpenAIRE

Huffenus , Alexandre; Pillonnet , Gaël; Abouchi , Nacer; Goutti , Frédéric

2010-01-01

International audience; This paper compares two modulation schemes for Class-D amplifiers: Phase-Shift Self-Oscillating (PSSO) and Carrier-Based Pulse Width Modulation (PWM). Theoretical analysis (modulation, frequency of oscillation, bandwidth…), design procedure, and IC silicon evaluation will be shown for mono and stereo operation (on the same silicon die) on both structures. The design of both architectures will use as many identical building blocks as possible, to provide a fair, "all el...

Activin and TGFβ use diverging mitogenic signaling in advanced colon cancer

OpenAIRE

Bauer, Jessica; Ozden, Ozkan; Akagi, Naomi; Carroll, Timothy; Principe, Daniel R.; Staudacher, Jonas J.; Spehlmann, Martina E.; Eckmann, Lars; Grippo, Paul J.; Jung, Barbara

2015-01-01

Background Understanding cell signaling pathways that contribute to metastatic colon cancer is critical to risk stratification in the era of personalized therapeutics. Here, we dissect the unique involvement of mitogenic pathways in a TGFβ or activin-induced metastatic phenotype of colon cancer. Method Mitogenic signaling/growth factor receptor status and p21 localization were correlated in primary colon cancers and intestinal tumors from either AOM/DSS treated ACVR2A (activin receptor 2) −/−...

Stress and vascular responses: atheroprotective effect of laminar fluid shear stress in endothelial cells: possible role of mitogen-activated protein kinases.

Science.gov (United States)

Yoshizumi, Masanori; Abe, Jun-Ichi; Tsuchiya, Koichiro; Berk, Bradford C; Tamaki, Toshiaki

2003-03-01

Atherosclerosis preferentially occurs in areas of turbulent blood flow and low fluid shear stress, whereas laminar blood flow and high shear stress are atheroprotective. Inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-alpha), stimulate expression of endothelial cell (EC) genes that may promote atherosclerosis. Recent findings suggest a steady laminar blood flow decreases EC apoptosis and inhibits TNF-mediated EC activation. EC apoptosis or activation is suggested to be involved in plaque erosion, which may lead to platelet aggregation. TNF-alpha regulates gene expression in ECs, in part, by stimulating mitogen-activated protein (MAP) kinases, which phosphorylate transcription factors. We hypothesized that steady laminar flow inhibits cytokine-mediated activation of MAP kinases in ECs. To test this hypothesis, we determined the effects of steady laminar flow (shear stress = 12 dynes/cm(2)) on TNF-alpha-stimulated activity of three MAP kinases in human umbilical vein ECs (HUVEC): extracellular signal-regulated kinase (ERK1/2), c-Jun N-terminal kinase (JNK), and p38. TNF-alpha activated ERK1/2, JNK, and p38 maximally at 15 min in HUVEC. Pre-exposing HUVEC for 10 min to flow inhibited TNF-alpha activation of JNK, but showed no significant effect on ERK1/2 or p38 activation. Incubation of HUVEC with PD98059, a specific ERK1/2 inhibitor, blocked the flow-mediated inhibition of TNF activation of JNK. Transfection studies with dominant-negative constructs of the protein kinase MEK5 suggested an important role for big mitogen-activated protein kinase 1 (BMK1) in flow-mediated regulation of EC activation by TNF-alpha. Understanding the mechanisms by which steady laminar flow regulates JNK activation by cytokines may provide insight into the atheroprotective mechanisms induced by laminar blood flow.

Regulator of differentiation 1 (ROD1) binds to the amphipathic C-terminal peptide of thrombospondin-4 and is involved in its mitogenic activity.

Science.gov (United States)

Sadvakassova, Gulzhakhan; Dobocan, Monica C; Difalco, Marcos R; Congote, Luis F

2009-09-01

The matrix protein thrombospondin-4 has an acidic amphipathic C-terminal peptide (C21) which stimulates erythroid cell proliferation. Here we show that C21 stimulates red cell formation in anemic mice in vivo. In vitro experiments indicated that the peptide-mediated increase of erythroid colony formation in cultures of human CD34+ hematopoietic progenitor cells was possible only under continuous presence of erythropoietin. In the absence of this cytokine, C21 stimulated exclusively myeloid colony formation. Therefore, the peptide is not a specific erythroid differentiation factor. In fact, it is mitogenic in non-erythroid cells, such as skin fibroblasts and kidney epithelial cells. In erythroleukemic TF-1 cells, it actually decreased the production of the erythroid differentiation marker glycophorin A. C21-affinity chromatography revealed regulator of differentiation 1 (ROD1) as a major C21-binding protein. ROD1 is the hematopoietic cell paralog of polypyrimidine tract binding proteins (PTBs), RNA splice regulators which regulate differentiation by repressing tissue-specific exons. ROD1 binding to C21 was strongly inhibited by synthetic RNAs in the order poly A > poly U > poly G = poly C and was weakly inhibited by a synthetic phosphorylated peptide mimicking the C-terminal domain of RNA polymerase II. Cellular overexpression or knockdown experiments of ROD1 suggest a role for this protein in the mitogenic activity of C21. Since the nuclear proteins ROD1 and PTBs regulate differentiation at a posttranscriptional level and there is a fast nuclear uptake of C21, we put forward the idea that the peptide is internalized, goes to the nucleus and maintains cells in a proliferative state by supporting ROD1-mediated inhibition of differentiation.

PWM Inverter control and the application thereof within electric vehicles

Science.gov (United States)

Geppert, Steven

1982-01-01

An inverter (34) which provides power to an A.C. machine (28) is controlled by a circuit (36) employing PWM control strategy whereby A.C. power is supplied to the machine at a preselectable frequency and preselectable voltage. This is accomplished by the technique of waveform notching in which the shapes of the notches are varied to determine the average energy content of the overall waveform. Through this arrangement, the operational efficiency of the A.C. machine is optimized. The control circuit includes a micro-computer and memory element which receive various parametric inputs and calculate optimized machine control data signals therefrom. The control data is asynchronously loaded into the inverter through an intermediate buffer (38). In its preferred embodiment, the present invention is incorporated within an electric vehicle (10) employing a 144 VDC battery pack (32) and a three-phase induction motor (18).

Design Research on Three-Phase PWM Rectifier Based on Double Closed Loop Control Technology

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Guang Ya LIU

2014-02-01

Full Text Available Based on the high frequency of three-phase voltage source PWM rectifier, this paper established a mathematical model of three phase current inner ring and outer ring voltage, and put forward the setting method of three phase double closed loop control. Finally, it was verified through simulation. The experimental results show that Three-phase output of DC voltage is stable with the operation of regulating systems, the current flowing into the grid tends to be sinusoidal and power factor is close to 1, which greatly reduce the interference of harmonics on the grid, thus improve grid operation.

Generation of reactive oxygen species (ROS) is a key factor for stimulation of macrophage proliferation by ceramide 1-phosphate

International Nuclear Information System (INIS)

Arana, Lide; Gangoiti, Patricia; Ouro, Alberto; Rivera, Io-Guané; Ordoñez, Marta; Trueba, Miguel; Lankalapalli, Ravi S.; Bittman, Robert; Gomez-Muñoz, Antonio

2012-01-01

We previously demonstrated that ceramide 1-phosphate (C1P) is mitogenic for fibroblasts and macrophages. However, the mechanisms involved in this action were only partially described. Here, we demonstrate that C1P stimulates reactive oxygen species (ROS) formation in primary bone marrow-derived macrophages, and that ROS are required for the mitogenic effect of C1P. ROS production was dependent upon prior activation of NADPH oxidase by C1P, which was determined by measuring phosphorylation of the p40phox subunit and translocation of p47phox from the cytosol to the plasma membrane. In addition, C1P activated cytosolic calcium-dependent phospholipase A 2 and protein kinase C-α, and NADPH oxidase activation was blocked by selective inhibitors of these enzymes. These inhibitors, and inhibitors of ROS production, blocked the mitogenic effect of C1P. By using BHNB-C1P (a photolabile caged-C1P analog), we demonstrate that all of these C1P actions are caused by intracellular C1P. It can be concluded that the enzyme responsible for C1P-stimulated ROS generation in bone marrow-derived macrophages is NADPH oxidase, and that this enzyme is downstream of PKC-α and cPLA 2 -α in this pathway. -- Highlights: ► Ceramide 1-phosphate (C1P) stimulates reactive oxygen species (ROS) formation. ► The enzyme responsible for ROS generation by C1P in macrophages is NADPH oxidase. ► NADPH oxidase lies downstream of cPLA 2 -α and PKC-α in this pathway. ► ROS generation is essential for the stimulation of macrophage proliferation by C1P.

Detection of clonal aberrations by cytogenetic analysis after different culture methods and by FISH in 129 patients with Chronic Lymphocytic Leukemia.

Science.gov (United States)

Jenderny, Jutta; Goldmann, Claudia; Thede, Rebekka; Ebrecht, Monika; Korioth, Frank

2014-01-01

There are only a few cytogenetic analysis (CA) studies that directly compare the novel cultivation technique using immunostimulatory CpG-oligonucleotide DSP30/interleukin-2 (DSP30/IL2) with other culture methods. Therefore, parallel cultures of peripheral blood of 129 chronic lymphocytic leukemia (CLL) patients were set up in unstimulated cultures, in the presence of pokeweed medium (PWM), and with DSP30/IL2. Furthermore, CA results were compared with data obtained by FISH. Clonal aberrations were observed by CA in 6% of the cases in unstimulated cultures, in 27% of the cases with PWM, and in 40% of the cases with DSP30/IL2. Some clonal aberrations were detected by CA only with one culture method. Using 3 different culture methods, clonal aberrations were detected in 41% of the cases by CA and in 71% of the cases by FISH. Altogether, 78% of the cases exhibited clonal aberrations discovered by CA and FISH. Also, CA detected clonal aberrations not targeted by FISH in 7% of the cases, and FISH identified clonal aberrations not detected by CA in 36% of the cases. Our study demonstrates that the combined use of CA with different culture methods together with FISH increases our knowledge of the genetic complexity and heterogeneity in CLL pathogenesis. © 2014 S. Karger AG, Basel.

Design of a ZVS PWM inverter for a brushless DC motor in an EMA application

Science.gov (United States)

Bell, J. Brett; Nelms, R. M.; Shepherd, Michael T.

1993-01-01

The Component Development Division of the Propulsion Laboratory at Marshall Space Flight Center (MSFC) is currently investigating the use of electromechanical actuators for use in space transportation applications such as Thrust Vector Control (TVC). These high power servomechanisms will require rugged, reliable, and compact power electronic modules capable of modulating several hundred amperes of current at up to 270 Vdc. This paper will discuss the design and implementation of a zero-voltage-switched PWM (Pulse Width Modulation) inverter which operates from a 270 Vdc source at currents up to 100 A.

Design of a ZVS PWM inverter for a brushless DC motor in an EMA application

Science.gov (United States)

Bell, J. Brett; Nelms, R. M.; Shepherd, Michael T.

The Component Development Division of the Propulsion Laboratory at Marshall Space Flight Center (MSFC) is currently investigating the use of electromechanical actuators for use in space transportation applications such as Thrust Vector Control (TVC). These high power servomechanisms will require rugged, reliable, and compact power electronic modules capable of modulating several hundred amperes of current at up to 270 Vdc. This paper will discuss the design and implementation of a zero-voltage-switched PWM (Pulse Width Modulation) inverter which operates from a 270 Vdc source at currents up to 100 A.

Studies on binding and mitogenic effect of insulin and insulin-like growth factor I in glomerular mesangial cells

International Nuclear Information System (INIS)

Conti, F.G.; Striker, L.J.; Lesniak, M.A.; MacKay, K.; Roth, J.; Striker, G.E.

1988-01-01

The mesangial cells are actively involved in regulating glomerular hemodynamics. Their overlying endothelium is fenestrated; therefore, these cells are directly exposed to plasma substances, including hormones such as insulin and insulin-like growth factor I (IGF-I). These peptides may contribute to the mesangial sclerosis and cellular hyperplasia that characterize diabetic glomerulopathy. We report herein the characterization of the receptors and the mitogenic effects of IGF-I and insulin on mouse glomerular mesangial cells in culture. The IGF-I receptor was characterized on intact cells. The Kd of the IGF-I receptor was 1.47 X 10(-9) M, and the estimated number of sites was 64,000 receptors/cell. The binding was time, temperature, and pH dependent, and the receptor showed down-regulation after exposure to serum. The expression of the receptor did not change on cells at different densities. The specific binding for insulin was too low to allow characterization of the insulin receptor on intact cells. However, it was possible to identify the insulin receptor in a wheat germ agglutinin-purified preparation of solubilized mesangial cells. This receptor showed the characteristic features of the insulin receptor, including pH dependence of binding and a curvilinear Scatchard plot. The mitogenic effects of insulin and IGF-I on mesangial cells were measured by the incorporation of [3H]thymidine into DNA. IGF-I was more potent than insulin. The half-maximal response to IGF-I stimulation occurred at 1.3 X 10(-10) M, and a similar increase with insulin was observed at concentrations in the range of 10(-7) M, suggesting that this insulin action was mediated through the IGF-I receptor. These data show that the mouse microvascular smooth muscle cells of the glomerulus express a cell surface receptor for IGF-I in vitro and that this peptide is a potent mitogen for these mesangial cells

Position control of an electro-pneumatic system based on PWM technique and FLC.

Science.gov (United States)

Najjari, Behrouz; Barakati, S Masoud; Mohammadi, Ali; Futohi, Muhammad J; Bostanian, Muhammad

2014-03-01

In this paper, modeling and PWM based control of an electro-pneumatic system, including the four 2-2 valves and a double acting cylinder are studied. Dynamic nonlinear behavior of the system, containing fast switching solenoid valves and a pneumatic cylinder, as well as electrical, magnetic, mechanical, and fluid subsystems are modeled. A DC-DC power converter is employed to improve solenoid valve performance and suppress system delay. Among different position control methods, a proportional integrator derivative (PID) controller and fuzzy logic controller (FLC) are evaluated. An experimental setup, using an AVR microcontroller is implemented. Simulation and experimental results verify the effectiveness of the proposed control strategies. Copyright © 2014 ISA. Published by Elsevier Ltd. All rights reserved.

Effects of sustained sleep restriction on mitogen-stimulated cytokines, chemokines and T helper 1/ T helper 2 balance in humans.

Directory of Open Access Journals (Sweden)

John Axelsson

Full Text Available BACKGROUND: Recent studies suggest that acute sleep deprivation disrupts cellular immune responses by shifting T helper (Th cell activity towards a Th2 cytokine profile. Since little is known about more long-term effects, we investigated how five days of sleep restriction would affect pro-inflammatory, chemotactic, Th1- and Th2 cytokine secretion. METHODS: Nine healthy males participated in an experimental sleep protocol with two baseline sleep-wake cycles (sleep 23.00-07.00 h followed by 5 days with restricted sleep (03.00-07.00 h. On the second baseline day and on the fifth day with restricted sleep, samples were drawn every third hour for determination of cytokines/chemokines (tumor necrosis factor alpha (TNF-α, interleukin (IL -1β, IL-2, IL-4 and monocyte chemoattractant protein-1 (MCP-1 after in vitro stimulation of whole blood samples with the mitogen phytohemagglutinin (PHA. Also leukocyte numbers, mononuclear cells and cortisol were analysed. RESULTS: 5-days of sleep restriction affected PHA-induced immune responses in several ways. There was a general decrease of IL-2 production (p<.05. A shift in Th1/Th2 cytokine balance was also evident, as determined by a decrease in IL2/IL4 ratio. No other main effects of restricted sleep were shown. Two significant interactions showed that restricted sleep resulted in increased TNF-α and MCP-1 in the late evening and early night hours (p's<.05. In addition, all variables varied across the 24 h day. CONCLUSIONS: 5-days of sleep restriction is characterized by a shift towards Th2 activity (i.e. lower 1L-2/IL-4 ratio which is similar to the effects of acute sleep deprivation and psychological stress. This may have implications for people suffering from conditions characterized by excessive Th2 activity like in allergic disease, such as asthma, for whom restricted sleep could have negative consequences.

A single-phase PWM controlled AC to DC converter based on control of unity displacement power factor

OpenAIRE

Funabiki, Shigeyuki

1990-01-01

A modified pulse-width modulation (PWM) technique that improves the displacement power factor and the input power factor of a single-phase AC to DC converter is discussed. The modified converter is shown to have a high input power factor and allows the of DC voltage from zero to more than the maximum value of the source voltage. The displacement power factor is unity, and the input power factor is almost unity in the wide range of current command

A Dual-Bridge LLC Resonant Converter with Fixed-Frequency PWM Control for Wide Input Applications

DEFF Research Database (Denmark)

Xiaofeng, Sun; Li, Xiaohua; Shen, Yanfeng

2017-01-01

This paper proposes a dual-bridge (DB) LLC resonant converter for wide input applications. The topology is an integration of a half-bridge (HB) LLC circuit and a full-bridge (FB) LLC circuit. The fixed-frequency PWM control is employed and a range of twice the minimum input voltage can be covered....... Compared with the traditional pulse frequency modulation (PFM) controlled HB/FB LLC resonant converter, the voltage gain range is independent of the quality factor and the magnetizing inductor has little influence on the voltage gain, which can simplify the parameter selection process and benefit...

Insulin resistance enhances the mitogen-activated protein kinase signaling pathway in ovarian granulosa cells.

Directory of Open Access Journals (Sweden)

Linghui Kong

Full Text Available The ovary is the main regulator of female fertility. Granulosa cell dysfunction may be involved in various reproductive endocrine disorders. Here we investigated the effect of insulin resistance on the metabolism and function of ovarian granulosa cells, and dissected the functional status of the mitogen-activated protein kinase signaling pathway in these cells. Our data showed that dexamethasone-induced insulin resistance in mouse granulosa cells reduced insulin sensitivity, accompanied with an increase in phosphorylation of p44/42 mitogen-activated protein kinase. Furthermore, up-regulation of cytochrome P450 subfamily 17 and testosterone and down-regulation of progesterone were observed in insulin-resistant mouse granulosa cells. Inhibition of p44/42 mitogen-activated protein kinase after induction of insulin resistance in mouse granulosa cells decreased phosphorylation of p44/42 mitogen-activated protein kinase, downregulated cytochrome P450 subfamily 17 and lowered progesterone production. This insulin resistance cell model can successfully demonstrate certain mechanisms such as hyperandrogenism, which may inspire a new strategy for treating reproductive endocrine disorders by regulating cell signaling pathways.

Heat- and radiation effects on the hemaglutinating- and mitogenic activity of phytohemaglutinins

International Nuclear Information System (INIS)

Mancini Filho, J.; Vizeu, D.M.; Lajolo, F.M.

1975-01-01

The effect of ionizing radiation on hemaglutinating and mitogenic activity of phytohemaglutinins (PHA) in solution is studied. 10 Krad (electron beam) are neede for the destruction of 50% of the aglutinating capacity. The mitogenic effect is more resistent to irradiation (70 Krad for 50% inactivation) may be because both effects are due to different molecules. Changes were also followed by electrophoresis in polyacrylamida. The resistence to irradiation showed to be exponential function of the concentration of PHA in solution. (author) [pt

One-Stage and Two-Stage Schemes of High Performance Synchronous PWM with Smooth Pulses-Ratio Changing

DEFF Research Database (Denmark)

Oleschuk, V.; Blaabjerg, Frede

2002-01-01

This paper presents detailed description of one-stage and two-stage schemes of a novel method of synchronous, pulsewidth modulation (PWM) for voltage source inverters for ac drive application. The proposed control functions provide accurate realization of different versions of voltage space vector...... modulation with synchronization of the voltage waveform of the inverter and with smooth pulse-ratio changing. Voltage spectra do not contain even harmonic and sub-harmonics (combined harmonics) during the whole control range including the zone of overmodulation. Examples of determination of the basic control...

Kinetics of human T-cell expression of LFA-1, IL-2 receptor, and ICAM-1 following antigenic stimulation in vitro

DEFF Research Database (Denmark)

Hviid, L; Felsing, A; Theander, T G

1993-01-01

-specific stimulation is available. In the present study we have examined phenotypic T-cell changes after in vitro stimulation by the antigens purified derivative of tuberculin (PPD) and tetanus toxoid (TT). We show that the well-established differences in kinetics of mitogen- and antigen-induced T-cell proliferation...... of all 3 surface antigens showed similar kinetics, and correlated with the magnitude of the lymphoproliferative response. By day 8 (PHA-stimulation) or day 12 (PPD or TT stimulation), the lymphoproliferative response was essentially completed, the expression of CD11a and CD54 had approached...

Inhibition of the mitogenic response to platelet-derived growth factor by terbinafine

International Nuclear Information System (INIS)

St Denny, I.H.; Glinka, K.G.; Nemecek, G.M.; Stuetz, A.

1987-01-01

Terbinafine (T;(E)-N-(6,6-dimethyl-2-hepten-4-ynyl)-N-methyl-1-naphthalenemethanamine), an antimycotic which inhibits fungal squalene epoxidase activity, was examined for its effects on platelet-derived growth factor (PDGF)-stimulated mitogenesis. The inclusion of 1.5-5μM T in fibroblast incubation media was associated with increased [ 3 H]thymidine incorporation into DNA in the presence and absence of PDGF. However, T at concentrations above 6μM reduced DNA synthesis in control and PDGF-exposed cultures to nearly undetectable levels. Under a phase-contrast microscope, fibroblasts appeared morphologically normal at T concentrations as high as 25 μM. Neither the uptake of [ 3 H]thymidine nor the specific binding of 125 I-PDGF to fibroblast receptors was significantly affected by 10 μM T. Furthermore, concentrations of T which antagonized the mitogenic response to PDGF also interfered with fibroblast growth factor-induced mitogenesis. Together, these data suggest that T has the ability to inhibit the in vitro action of PDGF via a post-receptor mechanism

Inhibition of the mitogenic response to platelet-derived growth factor by terbinafine

Energy Technology Data Exchange (ETDEWEB)

St. Denny, I.H.; Glinka, K.G.; Nemecek, G.M. (Sandoz Research Institute, East Hanover, NJ (USA)); Stuetz, A. (Sandoz Forschungsinstitut, Vienna (Austria))

1987-05-01

Terbinafine (T;(E)-N-(6,6-dimethyl-2-hepten-4-ynyl)-N-methyl-1-naphthalenemethanamine), an antimycotic which inhibits fungal squalene epoxidase activity, was examined for its effects on platelet-derived growth factor (PDGF)-stimulated mitogenesis. The inclusion of 1.5-5{mu}M T in fibroblast incubation media was associated with increased ({sup 3}H)thymidine incorporation into DNA in the presence and absence of PDGF. However, T at concentrations above 6{mu}M reduced DNA synthesis in control and PDGF-exposed cultures to nearly undetectable levels. Under a phase-contrast microscope, fibroblasts appeared morphologically normal at T concentrations as high as 25 {mu}M. Neither the uptake of ({sup 3}H)thymidine nor the specific binding of {sup 125}I-PDGF to fibroblast receptors was significantly affected by 10 {mu}M T. Furthermore, concentrations of T which antagonized the mitogenic response to PDGF also interfered with fibroblast growth factor-induced mitogenesis. Together, these data suggest that T has the ability to inhibit the in vitro action of PDGF via a post-receptor mechanism.

Effects of type I/type II interferons and transforming growth factor-beta on B-cell differentiation and proliferation. Definition of costimulation and cytokine requirements for immunoglobulin synthesis and expression.

Science.gov (United States)

Estes, D M; Tuo, W; Brown, W C; Goin, J

1998-12-01

In this report, we sought to determine the role of selected type I interferons [interferon-alpha (IFN-alpha) and interferon-tau (IFN-tau)], IFN-gamma and transforming growth factor-beta (TGF-beta) in the regulation of bovine antibody responses. B cells were stimulated via CD40 in the presence or absence of B-cell receptor (BCR) cross-linking. IFN-alpha enhanced IgM, IgG2 and IgA responses but did not enhance IgG1 responses. BCR signalling alone was more effective at inducing IgG2 responses with IFN-alpha than dual cross-linking with CD40. Recombinant ovine IFN-tau was less effective at inducing IgG2 responses when compared with IFN-alpha, though IgA responses were similar in magnitude following BCR cross-linking. At higher concentrations, IFN-tau enhanced IgA responses greater than twofold over the levels observed with IFN-alpha. Previous studies have shown that addition of IFN-gamma to BCR or pokeweed mitogen-activated bovine B cells stimulates IgG2 production. However, following CD40 stimulation alone, IFN-gamma was relatively ineffective at stimulating high-rate synthesis of any non-IgM isotype. Dual cross-linking via CD40 and the BCR resulted in decreased synthesis of IgM with a concomitant increase in IgA and similar levels of IgG2 production to those obtained via the BCR alone. We also assessed the effects of endogenous and exogenous TGF-beta on immunoglobulin synthesis by bovine B cells. Exogenous TGF-beta stimulates both IgG2 and IgA production following CD40 and BCR cross-linking in the presence of IL-2. Blocking endogenous TGF-beta did not inhibit the up-regulation of IgG2 or IgA by interferons.

Assessment of an Average Controller for a DC/DC Converter via Either a PWM or a Sigma-Delta-Modulator

Directory of Open Access Journals (Sweden)

R. Silva-Ortigoza

2014-01-01

Full Text Available Sliding mode control is a discontinuous control technique that is, by its nature, appropriate for controlling variable structure systems, such as the switch regulated systems employed in power electronics. However, when designing control laws based on the average models of these systems a modulator is necessary for their experimental implementation. Among the most widely used modulators in power electronics are the pulse width modulation (PWM and, more recently, the sigma-delta-modulator (Σ-Δ-modulator. Based on the importance of achieving an appropriate implementation of average control laws and the relevance of the trajectory tracking task in DC/DC power converters, for the first time, this research presents the assessment of the experimental results obtained when one of these controllers is implemented through either a PWM or a Σ-Δ-modulator to perform such a task. A comparative assessment based on the integral square error (ISE index shows that, at frequencies with similar efficiency, the Σ-Δ-modulator provides a better tracking performance for the DC/DC Buck converter. In this paper, an average control based on differential flatness was used to perform the experiments. It is worth mentioning that a different trajectory tracking controller could have been selected for this research.

T cell activation and proliferation following acute exercise in human subjects is altered by storage conditions and mitogen selection.

Science.gov (United States)

Siedlik, Jacob A; Deckert, Jake A; Benedict, Stephen H; Bhatta, Anuja; Dunbar, Amanda J; Vardiman, John P; Gallagher, Philip M

2017-07-01

Recent work investigating exercise induced changes in immunocompetence suggests that some of the ambiguity in the literature is resultant from different cell isolation protocols and mitogen selection. To understand this effect, we compared post-exercise measures of T cell activation and proliferation using two different stimulation methods (costimulation through CD28 or stimulation with phytohaemagglutinin [PHA]). Further, we investigated whether exercise induced changes are maintained when T cell isolation from whole blood is delayed overnight in either a room temperature or chilled (4°C) environment. As expected, an increased proliferation response was observed post-exercise in T cells isolated from whole blood of previously trained individuals immediately after blood collection. Also, cells stimulated with PHA after resting overnight in whole blood were not adversely impacted by the storage conditions. In contrast, allowing cells to rest overnight in whole blood prior to stimulation through CD28, lessened the proliferation observed by cells following exercise rendering both the room temperature and chilled samples closer to the results seen in the control condition. Changes in early markers of activation (CD25), followed a similar pattern, with activation in PHA stimulated cells remaining fairly robust after overnight storage; whereas cell activation following stimulation through CD3+CD28 was disproportionately decreased by the influence of overnight storage. These findings indicate that decisions regarding cell stimulation methods need to be paired with the timeline for T cell isolation from whole blood. These considerations will be especially important for field based studies of immunocompetence where there is a delay in getting whole blood samples to a lab for processing as well as clinical applications where a failure to isolate T cells in a timely manner may result in loss of the response of interest. Copyright © 2017 Elsevier B.V. All rights reserved.

Enhancement in irradiated mononuclear cells in culture of mitogen-induced incorporation of [3H]thymidine by homologous conditioned medium

International Nuclear Information System (INIS)

Sandru, G.; Greiner, R.

1994-01-01

Incorporation of [ 3 H]thymidine in irradiated peripheral blood mononuclear cell cultures irradiated in vitro was stimulated significantly by either concanavalin A or phytohemagglutinin only in the presence of homologous conditioned medium. Production of this activity by mononuclear cells was enhanced by irradiation and/or pulsed exposure to puromycin but was abolished by actinomycin D. Addition of anti-interleukin 1 or anti-interleukin 2 monoclonal antibodies to the conditioned medium before assay did not influence the stimulatory action. A similar significant stimulation of mononuclear cell cultures irradiated with 6 Gy by concanavalin A was obtained when purified preparations of homologous conditioned medium were used in the assay. Purification was done by ultrafiltration and concentration, heparin agarose chromatography, ammonium sulfate precipitation, concanavalin A agarose chromatography, DEAE-ion exchange chromatography and HPLC gel filtration chromatography. With SDS-PAGE and silver staining, the active HPLC fraction gave one band of 50 kDa, suggesting that this protein is responsible for the co-stimulatory effect of homologous conditioned medium for both mitogen-induced irradiated and nonirradiated mononuclear cell cultures. 42 refs., 9 figs., 3 tabs

TIMP-1 stimulates proliferation of human aortic smooth muscle cells and Ras effector pathways

International Nuclear Information System (INIS)

Akahane, Takemi; Akahane, Manabu; Shah, Amy; Thorgeirsson, Unnur P.

2004-01-01

Tissue inhibitor of metalloproteinases-1 (TIMP-1) is a multifunctional protein, which is found in most tissues and body fluids. Here, we demonstrated that recombinant TIMP-1 but not the synthetic matrix metalloproteinase inhibitor, GM6001, stimulated proliferation of human aortic smooth muscle cells (AoSMC) in a dose-dependent manner. The mitogenic effect was associated with activation of Ras, increased phosphorylation of ERK, and stimulation of cyclin D1 expression. The phosphatidylinositol 3-kinase (PI3K) signaling pathway was also involved since the PI3K inhibitor, LY294002, abolished the TIMP-1-mediated growth stimulation. These data suggest that TIMP-1 activates Ras, which then turns on the ERK and PI3K signaling pathways to promote cell cycle progression of the AoSMC

Cyclic nucleotides and mitogen-activated protein kinases: regulation of simvastatin in platelet activation

Directory of Open Access Journals (Sweden)

Hou Ssu-Yu

2010-06-01

Full Text Available Abstract Background 3-Hydroxy-3-methyl-glutaryl coenzyme A (HMG-CoA reductase inhibitors (statins have been widely used to reduce cardiovascular risk. These statins (i.e., simvastatin may exert other effects besides from their cholesterol-lowering actions, including inhibition of platelet activation. Platelet activation is relevant to a variety of coronary heart diseases. Although the inhibitory effect of simvastatin in platelet activation has been studied; the detailed signal transductions by which simvastatin inhibit platelet activation has not yet been completely resolved. Methods The aim of this study was to systematically examine the detailed mechanisms of simvastatin in preventing platelet activation. Platelet aggregation, flow cytometric analysis, immunoblotting, and electron spin resonance studies were used to assess the antiplatelet activity of simvastatin. Results Simvastatin (20-50 μM exhibited more-potent activity of inhibiting platelet aggregation stimulated by collagen than other agonists (i.e., thrombin. Simvastatin inhibited collagen-stimulated platelet activation accompanied by [Ca2+]i mobilization, thromboxane A2 (TxA2 formation, and phospholipase C (PLCγ2, protein kinase C (PKC, and mitogen-activated protein kinases (i.e., p38 MAPK, JNKs phosphorylation in washed platelets. Simvastatin obviously increased both cyclic AMP and cyclic GMP levels. Simvastatin markedly increased NO release, vasodilator-stimulated phosphoprotein (VASP phosphorylation, and endothelial nitric oxide synthase (eNOS expression. SQ22536, an inhibitor of adenylate cyclase, markedly reversed the simvastatin-mediated inhibitory effects on platelet aggregation, PLCγ2 and p38 MAPK phosphorylation, and simvastatin-mediated stimulatory effects on VASP and eNOS phosphorylation. Conclusion The most important findings of this study demonstrate for the first time that inhibitory effect of simvastatin in platelet activation may involve activation of the cyclic AMP

Common variable immunodeficiency in three horses with presumptive bacterial meningitis.

Science.gov (United States)

Pellegrini-Masini, Alessandra; Bentz, Amy I; Johns, Imogen C; Parsons, Corrina S; Beech, Jill; Whitlock, Robert H; Flaminio, M Julia B F

2005-07-01

Three adult horses were evaluated for signs of musculoskeletal pain, dullness, ataxia, and seizures. A diagnosis of bacterial meningitis was made on the basis of results of CSF analysis. Because primary bacterial meningitis is so rare in adult horses without any history of generalized sepsis or trauma, immune function testing was pursued. Flow cytometric phenotyping of peripheral blood lymphocytes was performed, and proliferation of peripheral blood lymphocytes in response to concanavalin A, phytohemagglutinin, pokeweed mitogen, and lipopolysaccharide was determined. Serum IgA, IgM, and IgG concentrations were measured by means of radial immunodiffusion, and serum concentrations of IgG isotypes were assessed with a capture antibody ELISA. Serum tetanus antibody concentrations were measured before and 1 month after tetanus toxoid administration. Phagocytosis and oxidative burst activity of isolated peripheral blood phagocytes were evaluated by means of simultaneous flow cytometric analysis. Persistent B-cell lymphopenia, hypogammaglobulinemia, and abnormal in vitro responses to mitogens were detected in all 3 horses, and a diagnosis of common variable immunodeficiency was made.

Advanced Control Strategy of Back-to-Back PWM Converters in PMSG Wind Power System

Directory of Open Access Journals (Sweden)

Tan Luong Van

2015-01-01

Full Text Available This paper proposes a control scheme of back-to-back PWM converters for the permanent magnet synchronous generator (PMSG wind turbine system. The DC-link voltage can be controlled at the machine-side converter (MSC, while the grid-side converter (GSC controls the grid active power for a maximum power point tracking (MPPT. At the grid fault condition, the DC-link voltage controller is designed using a feedback linearization (FL theory. For the MPPT, a proportional control loop is added to the torque control to reduce the influence of the inertia moment in the wind turbines, which can improve its dynamic performance. The validity of this control algorithm has been verified by the simulation of the 2-MW PMSG wind turbine system.

Contractions activate hormone-sensitive lipase in rat muscle by protein kinase C and mitogen-activated protein kinase

DEFF Research Database (Denmark)

Donsmark, Morten; Langfort, Jozef; Holm, Cecilia

2003-01-01

and contractions. Adrenaline acts via cAMP-dependent protein kinase (PKA). The signalling mediating the effect of contractions is unknown and was explored in this study. Incubated soleus muscles from 70 g male rats were electrically stimulated to perform repeated tetanic contractions for 5 min. The contraction......Intramuscular triacylglycerol is an important energy store and is also related to insulin resistance. The mobilization of fatty acids from this pool is probably regulated by hormone-sensitive lipase (HSL), which has recently been shown to exist in muscle and to be activated by both adrenaline......-induced activation of HSL was abolished by the protein kinase C (PKC) inhibitors bisindolylmaleimide I and calphostin C and reduced 50% by the mitogen-activated protein kinase kinase (MEK) inhibitor U0126, which also completely blocked extracellular signal-regulated kinase (ERK) 1 and 2 phosphorylation. None...

Subcellular distribution and mitogenic effect of basic fibroblast growth factor in mesenchymal uncommitted stem cells.

Science.gov (United States)

Benavente, Claudia A; Sierralta, Walter D; Conget, Paulette A; Minguell, José J

2003-06-01

Uncommitted mesenchymal stem cells (MSC), upon commitment and differentiation give rise to several mature mesenchymal lineages. Although the involvement of specific growth factors, including FGF2, in the development of committed MSC is known, the effect of FGF2 on uncommitted progenitors remains unclear. We have analyzed on a comparative basis, the subcellular distribution and mitogenic effect of FGF2 in committed and uncommitted MSC prepared from human bone marrow. Indirect immunofluorescence studies showed strong nuclear FGF2 staining in both progenitors; however, cytoplasmic staining was only detected in committed cells. Western blot analysis revealed the presence of 22.5 and 21-22 kDa forms of FGF2 in the nucleus of both progenitors; however, their relative content was higher in uncommitted than in committed cells. Exogenous FGF2 stimulated proliferation and sustained quiescence in committed and uncommitted cells, respectively. These results show that both type of progenitors, apart from morphological and proliferative differences, display specific patterns of response to FGF2.

Mitogenic Properties Of Lectin From Mucuna Sloanei Seed Extracts ...

African Journals Online (AJOL)

(p<0.05) increases in the values of the immunological parameters relative to those seen in the controls. This study, suggest that the isolated lectin from mucona sloanei seeds possesses mitogenic properties, and may be useful in the diagnosis and treatment of certain diseases such as blood typing disorders and obesity.

Transcriptional integration of mitogenic and mechanical signals by Myc and YAP.

Science.gov (United States)

Croci, Ottavio; De Fazio, Serena; Biagioni, Francesca; Donato, Elisa; Caganova, Marieta; Curti, Laura; Doni, Mirko; Sberna, Silvia; Aldeghi, Deborah; Biancotto, Chiara; Verrecchia, Alessandro; Olivero, Daniela; Amati, Bruno; Campaner, Stefano

2017-10-15

Mammalian cells must integrate environmental cues to determine coherent physiological responses. The transcription factors Myc and YAP-TEAD act downstream from mitogenic signals, with the latter responding also to mechanical cues. Here, we show that these factors coordinately regulate genes required for cell proliferation. Activation of Myc led to extensive association with its genomic targets, most of which were prebound by TEAD. At these loci, recruitment of YAP was Myc-dependent and led to full transcriptional activation. This cooperation was critical for cell cycle entry, organ growth, and tumorigenesis. Thus, Myc and YAP-TEAD integrate mitogenic and mechanical cues at the transcriptional level to provide multifactorial control of cell proliferation. © 2017 Croci et al.; Published by Cold Spring Harbor Laboratory Press.

Role of Piezo Channels in Ultrasound-stimulated Dental Stem Cells.

Science.gov (United States)

Gao, Qianhua; Cooper, Paul R; Walmsley, A Damien; Scheven, Ben A

2017-07-01

Piezo1 and Piezo2 are mechanosensitive membrane ion channels. We hypothesized that Piezo proteins may play a role in transducing ultrasound-associated mechanical signals and activate downstream mitogen-activated protein kinase (MAPK) signaling processes in dental cells. In this study, the expression and role of Piezo channels were investigated in dental pulp stem cells (DPSCs) and periodontal ligament stem cells (PDLSCs) after treatment with low-intensity pulsed ultrasound (LIPUS). Cell proliferation was evaluated by bromodeoxyuridine incorporation. Western blots were used to analyze the proliferating cell nuclear antigen as well as the transcription factors c-fos and c-jun. Enzyme-linked immunosorbent assay and Western blotting were used to determine the activation of MAPK after LIPUS treatment. Ruthenium red (RR), a Piezo ion channel blocker, was applied to determine the functional role of Piezo proteins in LIPUS-stimulated cell proliferation and MAPK signaling. Western blotting showed the presence of Piezo1 and Piezo2 in both dental cell types. LIPUS treatment significantly increased the level of the Piezo proteins in DPSCs after 24 hours; however, no significant effects were observed in PDLSCs. Treatment with RR significantly inhibited LIPUS-stimulated DPSC proliferation but not PDLSC proliferation. Extracellular signal-related kinase (ERK) 1/2 MAPK was consistently activated in DPSCs over a 24-hour time period after LIPUS exposure, whereas phosphorylated c-Jun N-terminal kinase and p38 mitogen-activated protein kinase MAPK were mainly increased in PDLSCs. RR affected MAPK signaling in both dental cell types with its most prominent effects on ERK1/2/MAPK phosphorylation levels; the significant inhibition of LIPUS-induced stimulation of ERK1/2 activation in DPSCs by RR suggests that stimulation of DPSC proliferation by LIPUS involves Piezo-mediated regulation of ERK1/2 MAPK signaling. This study for the first time supports the role of Piezo ion channels in

A Method of Maximum Power Control in Single-phase Utility Interactive Photovoltaic Generation System by using PWM Current Source Inverter

Science.gov (United States)

Neba, Yasuhiko

This paper deals with a maximum power point tracking (MPPT) control of the photovoltaic generation with the single-phase utility interactive inverter. The photovoltaic arrays are connected by employing the PWM current source inverter to the utility. The use of the pulsating dc current and voltage allows the maximum power point to be searched. The inverter can regulate the array voltage and keep the arrays to the maximum power. This paper gives the control method and the experimental results.

DMPD: Manipulation of mitogen-activated protein kinase/nuclear factor-kappaB-signalingcascades during intracellular Toxoplasma gondii infection. [Dynamic Macrophage Pathway CSML Database

Lifescience Database Archive (English)

Full Text Available 15361242 Manipulation of mitogen-activated protein kinase/nuclear factor-kappaB-sig...mmunol Rev. 2004 Oct;201:191-205. (.png) (.svg) (.html) (.csml) Show Manipulation of mitogen-activated prote... gondii infection. PubmedID 15361242 Title Manipulation of mitogen-activated protein kinase/nuclear factor-k

An inexpensive Arduino-based LED stimulator system for vision research.

Science.gov (United States)

Teikari, Petteri; Najjar, Raymond P; Malkki, Hemi; Knoblauch, Kenneth; Dumortier, Dominique; Gronfier, Claude; Cooper, Howard M

2012-11-15

Light emitting diodes (LEDs) are being used increasingly as light sources in life sciences applications such as in vision research, fluorescence microscopy and in brain-computer interfacing. Here we present an inexpensive but effective visual stimulator based on light emitting diodes (LEDs) and open-source Arduino microcontroller prototyping platform. The main design goal of our system was to use off-the-shelf and open-source components as much as possible, and to reduce design complexity allowing use of the system to end-users without advanced electronics skills. The main core of the system is a USB-connected Arduino microcontroller platform designed initially with a specific emphasis on the ease-of-use creating interactive physical computing environments. The pulse-width modulation (PWM) signal of Arduino was used to drive LEDs allowing linear light intensity control. The visual stimulator was demonstrated in applications such as murine pupillometry, rodent models for cognitive research, and heterochromatic flicker photometry in human psychophysics. These examples illustrate some of the possible applications that can be easily implemented and that are advantageous for students, educational purposes and universities with limited resources. The LED stimulator system was developed as an open-source project. Software interface was developed using Python with simplified examples provided for Matlab and LabVIEW. Source code and hardware information are distributed under the GNU General Public Licence (GPL, version 3). Copyright © 2012 Elsevier B.V. All rights reserved.

Mitogen-activated protein kinases in the acute diabetic myocardium

Czech Academy of Sciences Publication Activity Database

Strnisková, M.; Barančík, M.; Neckář, Jan; Ravingerová, T.

2003-01-01

Roč. 249, 1-2 (2003), s. 59-65 ISSN 0300-8177 R&D Projects: GA MŠk LN00A069 Grant - others:VEGA(SK) 2/2063/22 Institutional research plan: CEZ:AV0Z5011922 Keywords : experimental diabetes * ischemia * mitogen-activated protein kinases (MAPK) Subject RIV: ED - Physiology Impact factor: 1.763, year: 2003

Mitogen activated protein kinase signaling in the kidney: Target for intervention?

NARCIS (Netherlands)

de Borst, M.H.; Wassef, L.; Kelly, D.J.; van Goor, H.; Navis, Ger Jan

2006-01-01

Mitogen activated protein kinases (MAPKs) are intracellular signal transduction molecules, which connect cell-surface receptor signals to intracellular processes. MAPKs regulate a range of cellular activities including cell proliferation, gene expression, apoptosis, cell differentiation and cytokine

Internal-Model-Principle-Based Specific Harmonics Repetitive Controller for Grid-Connected PWM Inverters

Directory of Open Access Journals (Sweden)

Wenzhou Lu

2016-01-01

Full Text Available This paper analyzes the general properties of IMP-based controller and presents an internal-model-principle-based (IMP-based specific harmonics repetitive control (SHRC scheme. The proposed SHRC is effective for specific nk±m order harmonics, with n>m≥0 and k=0,1,2,…. Using the properties of exponential function, SHRC can also be rewritten into the format of multiple resonant controllers in parallel, where the control gain of SHRC is n/2 multiple of that of conventional RC (CRC. Therefore, including SHRC in a stable closed-loop feedback control system, asymptotic disturbance eliminating, or reference tracking for any periodic signal only including these specific harmonic components at n/2 times faster error convergence rate compared with CRC can be achieved. Application examples of SHRC controlled three-phase/single-phase grid-connected PWM inverters demonstrate the effectiveness and advantages of the proposed SHRC scheme.

MitoGen: A Framework for Generating 3D Synthetic Time-Lapse Sequences of Cell Populations in Fluorescence Microscopy.

Science.gov (United States)

Svoboda, David; Ulman, Vladimir

2017-01-01

The proper analysis of biological microscopy images is an important and complex task. Therefore, it requires verification of all steps involved in the process, including image segmentation and tracking algorithms. It is generally better to verify algorithms with computer-generated ground truth datasets, which, compared to manually annotated data, nowadays have reached high quality and can be produced in large quantities even for 3D time-lapse image sequences. Here, we propose a novel framework, called MitoGen, which is capable of generating ground truth datasets with fully 3D time-lapse sequences of synthetic fluorescence-stained cell populations. MitoGen shows biologically justified cell motility, shape and texture changes as well as cell divisions. Standard fluorescence microscopy phenomena such as photobleaching, blur with real point spread function (PSF), and several types of noise, are simulated to obtain realistic images. The MitoGen framework is scalable in both space and time. MitoGen generates visually plausible data that shows good agreement with real data in terms of image descriptors and mean square displacement (MSD) trajectory analysis. Additionally, it is also shown in this paper that four publicly available segmentation and tracking algorithms exhibit similar performance on both real and MitoGen-generated data. The implementation of MitoGen is freely available.

Salmonella Typhimurium type III secretion effectors stimulate innate immune responses in cultured epithelial cells.

Directory of Open Access Journals (Sweden)

Vincent M Bruno

2009-08-01

Full Text Available Recognition of conserved bacterial products by innate immune receptors leads to inflammatory responses that control pathogen spread but that can also result in pathology. Intestinal epithelial cells are exposed to bacterial products and therefore must prevent signaling through innate immune receptors to avoid pathology. However, enteric pathogens are able to stimulate intestinal inflammation. We show here that the enteric pathogen Salmonella Typhimurium can stimulate innate immune responses in cultured epithelial cells by mechanisms that do not involve receptors of the innate immune system. Instead, S. Typhimurium stimulates these responses by delivering through its type III secretion system the bacterial effector proteins SopE, SopE2, and SopB, which in a redundant fashion stimulate Rho-family GTPases leading to the activation of mitogen-activated protein (MAP kinase and NF-kappaB signaling. These observations have implications for the understanding of the mechanisms by which Salmonella Typhimurium induces intestinal inflammation as well as other intestinal inflammatory pathologies.

Somatomedin-C stimulates glycogen synthesis in fetal rat hepatocytes

International Nuclear Information System (INIS)

Freemark, M.; D'Ercole, A.J.; Handwerger, S.

1985-01-01

The effects of somatomedin-C/insulin-like growth factor I (Sm-C) on glycogen metabolism in cultured hepatocytes from 20-day-old rat fetuses have been examined and compared with the effects of insulin. Sm-C (25-375 ng/ml; 3.25-50 nM) stimulated dose-dependent increases in [ 14 C]glucose incorporation into glycogen (14.4-72.9% and total cell glycogen content (10.6-34.3%. Maximal stimulation of glycogen synthesis by Sm-C occurred at 2-4 h of incubation. Insulin (10 nM to 10 microM) also stimulated [ 14 C]glucose incorporation but its potency was only 1/20th that of Sm-C. The time course of stimulation of glucose incorporation by insulin was identical to that of Sm-C, the dose-response curves of the two hormones were parallel, and the maximal effects of insulin were not enhanced by simultaneous exposure of cells to Sm-C. These findings suggest that Sm-C and insulin stimulate glycogenesis in fetal liver through similar or identical mechanisms. Since the potency of Sm-C was 20 times greater than that of insulin, the glycogenic action of insulin in fetal liver may be mediated through binding to a hepatic receptor which also binds Sm-C. In addition to having mitogenic effects on fetal tissues, Sm-C may have direct anabolic effects on fetal carbohydrate metabolism

Expression, purification and crystallization of Streptococcus dysgalactiae-derived mitogen

International Nuclear Information System (INIS)

Papageorgiou, Anastassios C.; Saarinen, Susanna; Ramirez-Bartutis, Rosa; Kato, Hidehito; Uchiyama, Takehiko; Kirikae, Teruo; Miyoshi-Akiyama, Toru

2006-01-01

S. dysgalactiae-derived mitogen, a superantigen, was crystallized. Crystals diffract to 2.4 Å at a synchrotron-radiation source and belong to space group P3/P3 1 /P3 2 , with unit-cell parameters a = b = 52.7, c = 62.4 Å, γ = 120° and one molecule in the crystallographic asymmetric unit. Superantigens are bacterial or viral toxins with potent immunostimulatory properties. Streptococcus dysgalactiae-derived mitogen, a 25 kDa protein, is a recently discovered superantigen isolated from S. dysgalactiae culture supernatant. Sequence considerations suggest that it belongs to a new superantigen family distinct from other superantigens. The protein was expressed in Escherichia coli cells and purified to homogeneity. Crystals were grown at pH 4.2–4.4 in the presence of 18–20%(w/v) PEG 3350 and 0.4 M lithium nitrate. A complete data set to 2.4 Å resolution was collected from a single crystal at liquid-nitrogen temperatures using synchrotron radiation. The crystals belong to space group P3/P3 1 /P3 2 , with unit-cell parameters a = b = 52.7, c = 62.4 Å, γ = 120° and one molecule in the crystallographic asymmetric unit

Phase shift PWM with double two-switch bridge for high power capacitor charging

International Nuclear Information System (INIS)

Karandikar, U.S.; Singh, Yashpal; Thakurta, A.C.

2013-01-01

Pulse power supply systems working at higher voltage and high repetition rate demands for higher power from capacitor chargers. Capacitor charging requirement become more challenging in such cases. In pulse power circuits, energy storage capacitor should be charged to its desired voltage before the next switching occurs. It is discharged within a small time, delivering large pulse power. A capacitor charger has to work with wide load variation repeatedly. Many schemes are used for this purpose. The proposed scheme aims at reducing stresses on switches by reducing peak current and their evils. A high voltage power supply is designed for capacitor charging. The proposed scheme is based on a Phase-Shifted PWM without using any extra component to achieve soft switching. Indirect constant average current capacitor charging is achieved with a simple control scheme. A double two-switch bridge is proposed to enhance reliability. Power supply has been developed to charge a capacitor of 50 μF to 2.5 kV at 25 Hz. (author)

Performance optimization of a photovoltaic chain conversion by the PWM control

Science.gov (United States)

Rezoug, M. R.; Chenni, R.

2017-02-01

The interest of the research technique of maximum power point tracking, exposed by this article, lays in the fact of work instantly on the real characteristic of the photovoltaic module. This work is based on instantaneous measurements of its terminals' current & voltage as well as the exploitation of the characteristic "Power - Duty Cycle" to define rapidly the Duty cycle in which power reaches its maximum value. To ensure instantaneous tracking of the point of maximum power, we use "DC/DC Converter" based on "Pulse Wave Modulation's (PWM) Command" controlled by an algorithm implanted in a microcontroller's memory. This algorithm responds to the quick changes in climate (sunlight and temperature). To identify the control parameters "VPV & IPV" at any change in operating conditions, sensors are projected. this algorithm applied to the Duty cycle of the static converter enables the control of power supplied by the photovoltaic generator thanks to oscillatory movement around the MPP. Our article highlights the importance of this technique which lays in its simplicity and performance in changing climatic conditions. This efficiency is confirmed by experimental tests and this technique will improve its predecessors.

Autoradiographic research on cell proliferation of prenatal rat lung cells and their influence using the mitogen Kallikrein

International Nuclear Information System (INIS)

Bock-Lamberlin, P.R.

1980-01-01

In this work autoradiographic experiments were carried out on the kinetics of proliferation of four cell populations of the prenatal rat lung with the help of the determination of the 3 H-thymidine marker indices, with the following results: 1. The four studied cell populations exhibited variable proliferation rates on the twentieth or twenty-first day of development. 2. The strongest affect of the exogenously applied mitogen Kallikrein was demonstrated on the vessel wall cells, the next strongest on the bronchial epithelial cells, then the cartilage cells and finally the alveolar wall cells. 3. The mitogenic effect is dependent on dose. Higher doses significantly increased the 3 H-thymidine marker indices of the four cell populations tested in this work. 4. When the exposure time of the Kallikrein was extended by one hour this lead partially to stronger mitogenic effects than by the shorter exposure times at the same and higher dose levels of mitogen. 5. The 3 H-thymidine marker indices are dependent on the exposure time. 6. With increasing litter size, the 3 H indices as a rule decrease. (orig./MG) [de

A microculture system for generating haemolytic antibody responses from human tonsillar lymphocytes.

Science.gov (United States)

Booth, R J

1979-01-01

Small numbers of Ficoll-Hypaque purified human tonsillar lymphocytes were stimulated with PWM to produce SRBC-specific PFC in a microculture system. The magnitude of the response varied among different tonsils but was typically between 200 and 1000 PFC/10(6) cells cultured. Little or no response was observed in the absence of PWM. SRBC failed to stimulate a SRBC-specific response and the presence of this antigen in PWM-stimulated cultures depressed the response. The time of the maximum response was inversely related to the number of cells cultured. In addition, the duration of the response was limited by rapid depletion of critical medium requirements and/or build up of inhibitory factors especially when the cell concentration exceeded 5 x 10(5) cells/culture. This effect could be partially overcome by daily feeding of cultures with fresh medium. Fractionation studies indicated a requirement for both T and B cell populations. Constant efficiency of PFC production with respect to cell number could be achieved by the addition of inactivated autologous 'filler' cells. The significance of these results and applicability of the microculture system to a detailed analysis of human antibody responses will be discussed.

The measurement of cell mediated immunity by radioimmunoassay in desensitizing treatment with acupoints for allergic asthma

International Nuclear Information System (INIS)

Zhou Ronglin; Luan Meiling; Wang Mingsuo; Liu Keliang

1994-05-01

Three mitogens consisted of PHA, PWM, LPS were used to activate lymphocytes. Lymphocyte transformation with radioisotope incorporation of 3 H-TdR was done in 20 patients with allergic asthma and 14 healthy persons as control groups. Cell mediated immune in these cases of desensitizing treatment with acupoints were studied. The experiments showed that the incorporation rates of 3 H-TdR, acupoints were studied. The experiments showed that the incorporation rates of 3 H-TdR, activated by PHA, PWM, LPS, of the allergic asthma patients were P>0.05, P 3 H-TdR in lymphocytes after desensitizing treatment with acupoints compared with that before the treatment tended to be normal. Lymphocyte transformation difference of 3 H-TdR incorporation rates between this group and A or B control groups was significant (P<0.01). This study provides scientific clinical experimental evidences for researching cell mediated immune in attack and curative effects of allergic asthma

Design and implementation of high performance direct power control of three-phase PWM rectifier, via fuzzy and PI controller for output voltage regulation

International Nuclear Information System (INIS)

Bouafia, Abdelouahab; Krim, Fateh; Gaubert, Jean-Paul

2009-01-01

This paper proposes direct power control (DPC) for three-phase PWM rectifiers using a new switching table, without line voltage sensors. The instantaneous active and reactive powers, directly controlled by selecting the optimum state of the converter, are used as the PWM control variables instead of the phase line currents being used. The main goal of the control system is to maintain the dc-bus voltage at the required level, while input currents drawn from the power supply should be sinusoidal and in phase with respective phase voltages to satisfy the unity power factor (UPF) operation. Conventional PI and a designed fuzzy logic-based controller, in the dc-bus voltage control loop, have been used to provide active power command. A dSPACE based experimental system was developed to verify the validity of the proposed DPC. The steady-state, and dynamic results illustrating the operation and performance of the proposed control scheme are presented. As a result, it was confirmed that the novel DPC is much better than the classical one. Line currents very close to sinusoidal waveforms (THD < 2%) and good regulation of dc-bus voltage are achieved using PI or fuzzy controller. Moreover, fuzzy logic controller gives excellent performance in transient state, a good rejection of impact load disturbance, and a good robustness

Expression of human choline kinase in NIH 3T3 fibroblasts increases the mitogenic potential of insulin and insulin-like growth factor I.

Science.gov (United States)

Chung, T; Huang, J S; Mukherjee, J J; Crilly, K S; Kiss, Z

2000-05-01

In mammalian cells, growth factors, oncogenes, and carcinogens stimulate phosphocholine (PCho) synthesis by choline kinase (CK), suggesting that PCho may regulate cell growth. To validate the role of PCho in mitogenesis, we determined the effects of insulin, insulin-like growth factor I (IGF-I), and other growth factors on DNA synthesis in NIH 3T3 fibroblast sublines highly expressing human choline kinase (CK) without increasing phosphatidylcholine synthesis. In serum-starved CK expressor cells, insulin and IGF-I stimulated DNA synthesis, p70 S6 kinase (p70 S6K) activity, phosphatidylinositol 3-kinase (PI3K) activity, and activating phosphorylation of p42/p44 mitogen-activated protein kinases (MAPK) to greater extents than in the corresponding vector control cells. Furthermore, the CK inhibitor hemicholinium-3 (HC-3) inhibited insulin- and IGF-I-induced DNA synthesis in the CK overexpressors, but not in the vector control cells. The results indicate that high cellular levels of PCho potentiate insulin- and IGF-I-induced DNA synthesis by MAPK- and p70 S6K-regulated mechanisms.

Recruitment of focal adhesion kinase and paxillin to β1 integrin promotes cancer cell migration via mitogen activated protein kinase activation

International Nuclear Information System (INIS)

Crowe, David L; Ohannessian, Arthur

2004-01-01

Integrin-extracellular matrix interactions activate signaling cascades such as mitogen activated protein kinases (MAPK). Integrin binding to extracellular matrix increases tyrosine phosphorylation of focal adhesion kinase (FAK). Inhibition of FAK activity by expression of its carboxyl terminus decreases cell motility, and cells from FAK deficient mice also show reduced migration. Paxillin is a focal adhesion protein which is also phosphorylated on tyrosine. FAK recruitment of paxillin to the cell membrane correlates with Shc phosphorylation and activation of MAPK. Decreased FAK expression inhibits papilloma formation in a mouse skin carcinogenesis model. We previously demonstrated that MAPK activation was required for growth factor induced in vitro migration and invasion by human squamous cell carcinoma (SCC) lines. Adapter protein recruitment to integrin subunits was examined by co-immunoprecipitation in SCC cells attached to type IV collagen or plastic. Stable clones overexpressing FAK or paxillin were created using the lipofection technique. Modified Boyden chambers were used for invasion assays. In the present study, we showed that FAK and paxillin but not Shc are recruited to the β1 integrin cytoplasmic domain following attachment of SCC cells to type IV collagen. Overexpression of either FAK or paxillin stimulated cancer cell migration on type IV collagen and invasion through reconstituted basement membrane which was dependent on MAPK activity. We concluded that recruitment of focal adhesion kinase and paxillin to β1 integrin promoted cancer cell migration via the mitogen activated protein kinase pathway

Recruitment of focal adhesion kinase and paxillin to β1 integrin promotes cancer cell migration via mitogen activated protein kinase activation

Directory of Open Access Journals (Sweden)

Ohannessian Arthur

2004-05-01

Full Text Available Abstract Background Integrin-extracellular matrix interactions activate signaling cascades such as mitogen activated protein kinases (MAPK. Integrin binding to extracellular matrix increases tyrosine phosphorylation of focal adhesion kinase (FAK. Inhibition of FAK activity by expression of its carboxyl terminus decreases cell motility, and cells from FAK deficient mice also show reduced migration. Paxillin is a focal adhesion protein which is also phosphorylated on tyrosine. FAK recruitment of paxillin to the cell membrane correlates with Shc phosphorylation and activation of MAPK. Decreased FAK expression inhibits papilloma formation in a mouse skin carcinogenesis model. We previously demonstrated that MAPK activation was required for growth factor induced in vitro migration and invasion by human squamous cell carcinoma (SCC lines. Methods Adapter protein recruitment to integrin subunits was examined by co-immunoprecipitation in SCC cells attached to type IV collagen or plastic. Stable clones overexpressing FAK or paxillin were created using the lipofection technique. Modified Boyden chambers were used for invasion assays. Results In the present study, we showed that FAK and paxillin but not Shc are recruited to the β1 integrin cytoplasmic domain following attachment of SCC cells to type IV collagen. Overexpression of either FAK or paxillin stimulated cancer cell migration on type IV collagen and invasion through reconstituted basement membrane which was dependent on MAPK activity. Conclusions We concluded that recruitment of focal adhesion kinase and paxillin to β1 integrin promoted cancer cell migration via the mitogen activated protein kinase pathway.

Eotaxin induces degranulation and chemotaxis of eosinophils through the activation of ERK2 and p38 mitogen-activated protein kinases

DEFF Research Database (Denmark)

Kampen, G T; Stafford, S; Adachi, T

2000-01-01

Eotaxin and other CC chemokines acting via CC chemokine receptor-3 (CCR3) are believed to play an integral role in the development of eosinophilic inflammation in asthma and allergic inflammatory diseases. However, little is known about the intracellular events following agonist binding to CCR3...... and the relationship of these events to the functional response of the cell. The objectives of this study were to investigate CCR3-mediated activation of the mitogen-activated protein (MAP) kinases extracellular signal-regulated kinase-2 (ERK2), p38, and c-jun N-terminal kinase (JNK) in eosinophils and to assess...... the requirement for MAP kinases in eotaxin-induced eosinophil cationic protein (ECP) release and chemotaxis. MAP kinase activation was studied in eotaxin-stimulated eosinophils (more than 97% purity) by Western blotting and immune-complex kinase assays. ECP release was measured by radioimmunoassay. Chemotaxis...

Vibration and acoustic noise emitted by dry-type air-core reactors under PWM voltage excitation

Science.gov (United States)

Li, Jingsong; Wang, Shanming; Hong, Jianfeng; Yang, Zhanlu; Jiang, Shengqian; Xia, Shichong

2018-05-01

According to coupling way between the magnetic field and the structural order, structure mode is discussed by engaging finite element (FE) method and both natural frequency and modal shape for a dry-type air-core reactor (DAR) are obtained in this paper. On the basis of harmonic response analysis, electromagnetic force under PWM (Pulse Width Modulation) voltage excitation is mapped with the structure mesh, the vibration spectrum is gained and the consequences represents that the whole structure vibration predominates in the radial direction, with less axial vibration. Referring to the test standard of reactor noise, the rules of emitted noise of the DAR are measured and analyzed at chosen switching frequency matches the sample resonant frequency and the methods of active vibration and noise reduction are put forward. Finally, the low acoustic noise emission of a prototype DAR is verified by measurement.

Expression, purification and crystallization of Streptococcus dysgalactiae-derived mitogen

Energy Technology Data Exchange (ETDEWEB)

Papageorgiou, Anastassios C., E-mail: tassos.papageorgiou@btk.fi; Saarinen, Susanna; Ramirez-Bartutis, Rosa [Turku Centre for Biotechnology, University of Turku and Åbo Akademi University, Turku 20521 (Finland); Kato, Hidehito; Uchiyama, Takehiko [Department of Microbiology and Immunology, Tokyo Women’s Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666 (Japan); Kirikae, Teruo; Miyoshi-Akiyama, Toru [Department of Infectious Diseases, International Medical Center of Japan, 1-21-1 Toyama, Shinjuku-ku, Tokyo 162-8655 (Japan); Turku Centre for Biotechnology, University of Turku and Åbo Akademi University, Turku 20521 (Finland)

2006-03-01

S. dysgalactiae-derived mitogen, a superantigen, was crystallized. Crystals diffract to 2.4 Å at a synchrotron-radiation source and belong to space group P3/P3{sub 1}/P3{sub 2}, with unit-cell parameters a = b = 52.7, c = 62.4 Å, γ = 120° and one molecule in the crystallographic asymmetric unit. Superantigens are bacterial or viral toxins with potent immunostimulatory properties. Streptococcus dysgalactiae-derived mitogen, a 25 kDa protein, is a recently discovered superantigen isolated from S. dysgalactiae culture supernatant. Sequence considerations suggest that it belongs to a new superantigen family distinct from other superantigens. The protein was expressed in Escherichia coli cells and purified to homogeneity. Crystals were grown at pH 4.2–4.4 in the presence of 18–20%(w/v) PEG 3350 and 0.4 M lithium nitrate. A complete data set to 2.4 Å resolution was collected from a single crystal at liquid-nitrogen temperatures using synchrotron radiation. The crystals belong to space group P3/P3{sub 1}/P3{sub 2}, with unit-cell parameters a = b = 52.7, c = 62.4 Å, γ = 120° and one molecule in the crystallographic asymmetric unit.

Sustained improvement of intractable rheumatoid arthritis after total lymphoid irradiation

International Nuclear Information System (INIS)

Field, E.H.; Strober, S.; Hoppe, R.T.

1983-01-01

Total lymphoid irradiation (TLI) was administered to 11 patients who had intractable rheumatoid arthritis that was unresponsive to conventional medical therapy, including aspirin, multiple nonsteroidal antiinflammatory drugs, gold salts, and D-penicillamine. Total lymphoid irradiation was given as an alternative to cytotoxic drugs such as azathioprine and cyclophosphamide. After radiotherapy, 9 of the 11 patients showed a marked improvement in clinical disease activity as measured by morning stiffness, joint tenderness, joint swelling, and overall functional abilities. The mean improvement of disease activity in all patients ranged from 40-70 percent and has persisted throughout a 13-28 month followup period. This improvement permitted the mean daily steroid dose to be reduced by 54%. Complications included severe fatigue and other constitutional symptoms during radiotherapy, development of Felty's syndrome in 1 patient, and an exacerbation of rheumatoid lung disease in another. After therapy, all patients exhibited a profound T lymphocytopenia, and a reversal in their T suppressor/cytotoxic cell to helper cell ratio. The proliferative responses of peripheral blood mononuclear cells to phytohemagglutinin, concanavalin A, and allogeneic leukocytes (mixed leukocyte reaction) were markedly reduced, as was in vitro immunoglobulin synthesis after stimulation with pokeweed mitogen. Alterations in T cell numbers and function persisted during the entire followup period, except that the mixed leukocyte reaction showed a tendency to return to normal values

Selective Expansion of Memory CD4+ T cells By Mitogenic Human CD28 Generates Inflammatory Cytokines and Regulatory T cells

Science.gov (United States)

Singh, Manisha; Basu, Sreemanti; Camell, Christina; Couturier, Jacob; Nudelman, Rodolfo J.; Medina, Miguel A.; Rodgers, John R.; Lewis, Dorothy E.

2009-01-01

Co-stimulatory signals are important for development of effector and regulatory T cells. In this case, CD28 signaling is usually considered inert in the absence of signaling through the TCR. By contrast, mitogenic rat CD28 mAbs reportedly expand regulatory T cells without TCR stimulation. We found that a commercially available human CD28 mAb (ANC28) stimulated PBMCs without TCR co-ligation or cross-linking; ANC28 selectively expanded CD4+CD25+FoxP3−(T effector) and CD4+CD25+FoxP3+ (Treg) cells. ANC28 stimulated the CD45RO+ CD4+ (memory) population whereas CD45RA+CD4+ (naïve) cells did not respond. ANC28 also induced inflammatory cytokines. Treg induced by ANC28 retain the Treg phenotype longer than did co-stimulated Treg. Treg induced by ANC28 suppressed CD25− T cells through a contact-dependent mechanism. Purity influenced the response of CD4+CD25+ cells because bead-purified CD4+CD25+ cells (85–90% pure) responded strongly to ANC28, whereas 98% pure FACS-sorted CD4+CD25 bright (T-reg) did not respond. Purified CD4+CD25int cells responded similarly to the bead-purified CD4+CD25+ cells. Thus, pre-activated CD4+ T cells (CD25int) respond to ANC28 rather than Treg (CD25bright). The ability of ANC28 to expand both effectors producing inflammatory cytokines as well as suppressive regulatory T cells might be useful for ex vivo expansion of therapeutic T cells. PMID:18446791

Cellular reprogramming through mitogen-activated protein kinases

Directory of Open Access Journals (Sweden)

Justin eLee

2015-10-01

Full Text Available Mitogen-activated protein kinase (MAPK cascades are conserved eukaryote signaling modules where MAPKs, as the final kinases in the cascade, phosphorylate protein substrates to regulate cellular processes. While some progress in the identification of MAPK substrates has been made in plants, the knowledge on the spectrum of substrates and their mechanistic action is still fragmentary. In this focused review, we discuss the biological implications of the data in our original paper (Sustained mitogen-activated protein kinase activation reprograms defense metabolism and phosphoprotein profile in Arabidopsis thaliana; Frontiers in Plant Science 5: 554 in the context of related research. In our work, we mimicked in vivo activation of two stress-activated MAPKs, MPK3 and MPK6, through transgenic manipulation of Arabidopsis thaliana and used phosphoproteomics analysis to identify potential novel MAPK substrates. Here, we plotted the identified putative MAPK substrates (and downstream phosphoproteins as a global protein clustering network. Based on a highly stringent selection confidence level, the core networks highlighted a MAPK-induced cellular reprogramming at multiple levels of gene and protein expression – including transcriptional, post-transcriptional, translational, post-translational (such as protein modification, folding and degradation steps, and also protein re-compartmentalization. Additionally, the increase in putative substrates/phosphoproteins of energy metabolism and various secondary metabolite biosynthesis pathways coincides with the observed accumulation of defense antimicrobial substances as detected by metabolome analysis. Furthermore, detection of protein networks in phospholipid or redox elements suggests activation of downstream signaling events. Taken in context with other studies, MAPKs are key regulators that reprogram cellular events to orchestrate defense signaling in eukaryotes.

Sphingosine-1-phosphate stimulates rat primary chondrocyte proliferation

International Nuclear Information System (INIS)

Kim, Mi-Kyoung; Lee, Ha Young; Kwak, Jong-Young; Park, Joo-In; Yun, Jeanho; Bae, Yoe-Sik

2006-01-01

Rat primary chondrocytes express the sphingosine-1-phosphate (S1P) receptor, S1P 2 , S1P 3 , S1P 4 , but not S1P 1 . When chondrocytes were stimulated with S1P or phytosphingosine-1-phosphate (PhS1P, an S1P 1 - and S1P 4 -selective agonist), phospholipase C-mediated cytosolic calcium increase was dramatically induced. S1P and PhS1P also stimulated two kinds of mitogen-activated protein kinases, extracellular signal-regulated kinase (ERK) and p38 kinase in chondrocytes. In terms of the two phospholipids-mediated functional modulation of chondrocytes, S1P and PhS1P stimulated cellular proliferation. The two phospholipids-induced chondrocyte proliferations were almost completely blocked by PD98059 but not by SB203580, suggesting that ERK but not p38 kinase is essentially required for the proliferation. Pertussis toxin almost completely inhibited the two phospholipids-induced cellular proliferation and ERK activation, indicating the crucial role of G i protein. This study demonstrates the physiological role of two important phospholipids (S1P and PhS1P) on the modulation of rat primary chondrocyte proliferation, and the crucial role played by ERK in the process

High benefits approach for electrical energy conversion in electric vehicles from DC to PWM-AC without any generated harmonic

International Nuclear Information System (INIS)

Fathabadi, Hassan

2014-01-01

Highlights: • Novel hybrid power source including AC feature for using in electric/hybrid vehicles. • Minimizing the energy loss in electric/hybrid vehicles by using the proposed system. • Suitable AC wave form for braking/accelerating purposes in electric/hybrid vehicles. • A novelty is that the harmonic generated by the added AC feature is really zero. • Another novelty is the capability of choosing arbitrary frequency for AC feature. - Abstract: This paper presents a novel hybrid power source, including a Li-ion battery together with an interface, which generates simultaneously electrical energy with the forms of both DC and AC for electric vehicles. A novel and high benefits approach is applied to convert the electrical energy of the Li-ion battery from DC form to single-phase symmetric pulse-width modulation (PWM)-AC form. Harmonic generation is one of the important problems when electrical energy is converted from DC to AC but there are not any generated harmonic during the DC/AC conversion using the proposed technique. The proposed system will be widely used in electric/hybrid vehicles because it has many benefits. Minimizing the energy loss (saving energy), no generated harmonic (it is really zero), the capability of arbitrary/necessary frequency selection for output AC voltage and the ability of long distance energy transmission are some novelties and advantages of the proposed system. The proposed hybrid power source including DC/AC PWM inverter is simulated in Proteus 6 software environment and a laboratory-based prototype of the hybrid power source is constructed to validate the theoretical and simulation results. Simulation and experimental results are presented to prove the superiority of the proposed hybrid power supply

A study on stimulation of DC high voltage power of LCC series parallel resonant in projectile velocity measurement system

Science.gov (United States)

Lu, Dong-dong; Gu, Jin-liang; Luo, Hong-e.; Xia, Yan

2017-10-01

According to specific requirements of the X-ray machine system for measuring velocity of outfield projectile, a DC high voltage power supply system is designed for the high voltage or the smaller current. The system comprises: a series resonant circuit is selected as a full-bridge inverter circuit; a high-frequency zero-current soft switching of a high-voltage power supply is realized by PWM output by STM32; a nanocrystalline alloy transformer is chosen as a high-frequency booster transformer; and the related parameters of an LCC series-parallel resonant are determined according to the preset parameters of the transformer. The concrete method includes: a LCC series parallel resonant circuit and a voltage doubling circuit are stimulated by using MULTISM and MATLAB; selecting an optimal solution and an optimal parameter of all parts after stimulation analysis; and finally verifying the correctness of the parameter by stimulation of the whole system. Through stimulation analysis, the output voltage of the series-parallel resonant circuit gets to 10KV in 28s: then passing through the voltage doubling circuit, the output voltage gets to 120KV in one hour. According to the system, the wave range of the output voltage is so small as to provide the stable X-ray supply for the X-ray machine for measuring velocity of outfield projectile. It is fast in charging and high in efficiency.

A CMOS/SOI Single-input PWM Discriminator for Low-voltage Body-implanted Applications

Directory of Open Access Journals (Sweden)

Jader A. De Lima

2002-01-01

Full Text Available A CMOS/SOI circuit to decode Pulse-Width Modulation (PWM signals is presented as part of a body-implanted neurostimulator for visual prosthesis. Since encoded data is the sole input to the circuit, the decoding technique is based on a novel double-integration concept and does not require low-pass filtering. Non-overlapping control phases are internally derived from the incoming pulses and a fast-settling comparator ensures good discrimination accuracy in the megahertz range. The circuit was integrated on a 2 μm single-metal thin-film CMOS/SOI fabrication process and has an effective area of 2 mm2. Measured resolution of encoding parameter α is better than 10% at 6 MHz and VDD = 3.3 V. Idle-mode consumption is 340 μW. Pulses of frequencies up to15 MHz and α =10% can be discriminated for 2.3 V ≤ VDD ≤ 3.3 V. Such an excellent immunity to VDD deviations meets a design specification with respect to inherent coupling losses on transmitting data and power by means of a transcutaneous link.

PWM Regulation of Grid-Tied PV System on the Base of Photovoltaic-Fed Diode-Clamped Inverters

Directory of Open Access Journals (Sweden)

Oleschuk V.I.

2015-12-01

Full Text Available Investigation of grid-tied photovoltaic system on the base of two diode-clamped inverters, controlled by specific algorithms of pulse-width modulation (PWM, has been done. This system includes two strings of photovoltaic panels feeding two diode-clamped inverters. The outputs of inverters are connected with the corresponding windings on the primary side of three-phase transformer, connected with a grid. In order to reduce phase voltage distortion and to increase efficiency of operation of the system, special scheme of control and modulation of inverters has been used, providing minimization of common-mode voltages and voltage waveforms symmetries under different operating conditions. Detailed simulation of processes in this photovoltaic-fed power conversion system has been executed. The results of simulations verify good performance of photovoltaic system regulated in accordance with specific strategy of control and modulation.

Evaluation of the potential immunotoxicity of 3-monochloro-1,2-propanediol in Balb/c mice I. Effect on antibody forming cell, mitogen-stimulated lymphocyte proliferation, splenic subset, and natural killer cell activity

International Nuclear Information System (INIS)

Lee, Jong Kwon; Byun, Jung A.; Park, Seung Hee; Kim, Hyung Soo; Park, Jae Hyun; Eom, Juno H.; Oh, Hye Young

2004-01-01

3-Monochloro-1,2-propanediol (MCPD) is a well-known by-product of acid-hydrolyzed soy sauce during its manufacturing process. MCPD has been reported genotoxic in vitro, and reproductive toxicity and carcinogenicity in rats. However, no previous studies have investigated MCPD-induced alterations in the immune system. In the present study, MCPD was administered by gavage for 14 days at 0, 25, 50, and 100 mg/kg per day to female Balb/c mice. The antibody-mediated immune response to sheep red blood cells (SRBC) was assessed using the antibody-forming cell (AFC) assay, and splenic cell phenotypes were quantified by flow cytometry. Hematological and histopathological changes were assessed. Mitogen-stimulated spleen lymphocyte proliferation and natural killer (NK) cell activity were evaluated. The T-lymphocyte blastogenesis by concanavalin A (Con A) or anti-CD3 and B-lymphocyte blastogenesis by lipopolysaccharide (LPS) were not significantly changed. There were no significant changes in the hematological and histopathological findings of MCPD-treated mice. However, the significant decrease in thymus weight was observed in 100 mg dose group, even though that did not change body weight gain. The cellularities of spleen and thymus were significantly reduced in high-dose group. Exposure to high dose of MCPD decreased the AFC response to SRBC in mice. There was a significant decrease in NK cell activity of mice treated with high dose of MCPD. These results indicate that MCPD could modulate the immune function in Balb/c mice

Ligand binding affinity at the insulin receptor isoform A (IR-A and subsequent IR-A tyrosine phosphorylation kinetics are important determinants of mitogenic biological outcomes.

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Harinda eRajapaksha

2015-07-01

Full Text Available The insulin receptor (IR is a tyrosine kinase receptor that can mediate both metabolic and mitogenic biological actions. The IR isoform-A (IR-A arises from alternative splicing of exon 11 and has different ligand binding and signalling properties compared to the IR isoform-B. The IR-A not only binds insulin but also insulin-like growth factor-II (IGF-II with high affinity. IGF-II acting through the IR-A promotes cancer cell proliferation, survival and migration by activating some unique signalling molecules compared to those activated by insulin. This observation led us to investigate whether the different IR-A signalling outcomes in response to IGF-II and insulin could be attributed to phosphorylation of a different subset of IR-A tyrosine residues or to the phosphorylation kinetics. We correlated IR-A phosphorylation to activation of molecules involved in mitogenic and metabolic signalling (MAPK and Akt and receptor internalisation rates (related to mitogenic signalling. We also extended this study to incorporate two ligands that are known to promote predominantly mitogenic ([His4, Tyr15, Thr49, Ile51] IGF-I, qIGF-I or metabolic (S597 peptide biological actions, to see if common mechanisms can be used to define mitogenic or metabolic signalling through the IR-A. The 3-fold lower mitogenic action of IGF-II compared to insulin was associated with a decreased potency in activation of Y960, Y1146, Y1150, Y1151, Y1316 and Y1322, in MAPK phosphorylation and in IR-A internalization. With the poorly mitogenic S597 peptide it was a decreased rate of tyrosine phosphorylation rather than potency that was associated with a low mitogenic potential. We conclude that both decreased affinity of IR-A binding and the kinetics of IR-A phosphorylation can independently lead to a lower mitogenic activity. None of the studied parameters could account for the lower metabolic activity of qIGF-I.

A nonlinear adaptive backstepping approach applied to a three phase PWM AC-DC converter feeding induction heating

Science.gov (United States)

Hadri-Hamida, A.; Allag, A.; Hammoudi, M. Y.; Mimoune, S. M.; Zerouali, S.; Ayad, M. Y.; Becherif, M.; Miliani, E.; Miraoui, A.

2009-04-01

This paper presents a new control strategy for a three phase PWM converter, which consists of applying an adaptive nonlinear control. The input-output feedback linearization approach is based on the exact cancellation of the nonlinearity, for this reason, this technique is not efficient, because system parameters can vary. First a nonlinear system modelling is derived with state variables of the input current and the output voltage by using power balance of the input and output, the nonlinear adaptive backstepping control can compensate the nonlinearities in the nominal system and the uncertainties. Simulation results are obtained using Matlab/Simulink. These results show how the adaptive backstepping law updates the system parameters and provide an efficient control design both for tracking and regulation in order to improve the power factor.

Similar disturbances in B cell activity and regulatory T cell function in Henoch-Schonlein purpura and systemic lupus erythematosus

International Nuclear Information System (INIS)

Beale, M.G.; Nash, G.S.; Bertovich, M.J.; MacDermott, R.P.

1982-01-01

The immunoglobulin synthesizing activities of peripheral mononuclear cells (MNC) from five patients with Henoch-Schonlein purpura (HSP) and eight patients with active systemic lupus erythematosus (SLE) were compared. Cumulative amounts of IgM, IgG, and IgA synthesized and secreted by unstimulated and PWM-stimulated patient cells over a 12-day period were determied in a solid-phase radioimmunoassay. In unstimulated control cultures mean rates of IgM, IgG, and IgA synthesis were less than 250 ng/ml. The synthetic activities of patient MNC were markedly increased. In HSP cultures IgA was the major immunoglobulin class produced (2810 x/divide 1.33 ng/ml) followed by IgG (1754 x/divide 1.32 ng/ml) and IgM (404 x/divide 1.16 ng/ml). In SLE cultures IgA and IgG syntheses were equally elevated (4427 x/divide 1.20 and 4438 x/divide 1.49 ng/ml, respectively) whereas IgM synthesis averaged 967 x/divide 1.66 ng/ml. PWM stimulation of pateient MNC caused a sharp decline in the synthesis of all three immunoglobulin classes. After T cell depletion B cell-enriched fractions from HSP and SLE patients maintained high levels of IgA and IgG synthesis that were inhibited by PWM and by normal allogeneic but not autologous T cells. In PWM-stimulted co-cultures, patient T cells nonspecifically suppressed the synthetic activities of autologous and control B cells. in contrast patient B cells achieved normal levels of immunoglobulin synthesis when cultured with control T cells plus PWM. In longitudinal studies patient B and T cell disturbances persisted despite clinical improvement

Mesenchymal stem cells inhibit lymphocyte proliferation by mitogens and alloantigens by different mechanisms

International Nuclear Information System (INIS)

Rasmusson, Ida; Ringden, Olle; Sundberg, Berit; Le Blanc, Katarina

2005-01-01

Human mesenchymal stem cells (MSCs) have immuno-modulatory properties. They inhibit T-cell proliferation to mitogens and alloantigens in vitro and prolong skin graft survival in vivo. We found that MSCs inhibited the proliferation of peripheral blood lymphocytes (PBLs) to phorbol myristate acetate (PMA), suggesting that MSCs exert an inhibitory effect downstream of the receptor level. We analyzed cytokine profiles of PBLs co-cultured with MSCs. MSCs increased interleukin (IL)-2 and soluble IL-2 receptor in mixed lymphocyte cultures (MLCs), while IL-2 and IL-2R decreased in phytohemagglutinin (PHA)-stimulated PBL cultures. MSCs inhibited IL-2 induced proliferation, without absorbing IL-2. IL-10 levels increased in MLCs co-cultured with 10% MSCs, while the levels were not affected in PHA cultures. In MLCs inhibited by MSCs, antibodies against IL-10 further suppressed proliferation but had no effect in PHA cultures. Addition of indomethacin, an inhibitor of prostaglandin-synthesis, restored part of the inhibition by MSCs in PHA cultures. However, indomethacin did not affect MSC-induced inhibition in MLCs. To conclude, our data indicate that MSC-induced suppression is a complex mechanism affecting IL-2 and IL-10 signaling and may function differently, depending on T-cell stimuli. Prostaglandins are important in the inhibition by MSCs when the T cells were activated by PHA, but not alloantigens

Desain dan Realisasi Sistem Komunikasi Cahaya Tampak untuk Streaming Teks berbasis PWM

Directory of Open Access Journals (Sweden)

Trio Adiono

2017-12-01

Full Text Available The design and implementation of visible light communication systems for transmitting digital data (texts have been discussed in this paper. Then, two evaluations were performed also, i.e. the demonstration of streaming text through the visible light as a proof-of-concept system design. The next evaluation is a BER measurement intended to know the VLC system performance quantitatively. The value of BER against the several parameters: by the variation of distance and its reception angle. The proposed VLC system works well until the photodiode reception angle to the LEDs up to 50°. According to evaluation, our system can operate optimally within 30 – 80 cm or 50 – 130 cm of optical channel range depending on the Gain setting option. To support the reliability of noise from ambient light and interference lamps such as fluorescent lamps, the filters circuit are employed: high pass filter and DC-offset remover. Based on the BER analysis, the filters can compensate the problem of ambient light noise (DC-offset signal and interference lamp (100-150 Hz of carrier frequency. The speed of data-rate obtained with 1-PWM modulation and the low-cost analog component is 3.3 kbps.

The effect of midazolam on neutrophil mitogen-activated protein kinase.

LENUS (Irish Health Repository)

Ghori, Kamran

2010-06-01

Neutrophil p38 mitogen-activated protein kinase (MAPK) is a key enzyme in the intracellular signalling pathway that is responsible for many neutrophil functions, which are important in neutrophil-endothelial interaction. The imidazole compounds are inhibitors of this enzyme system. The objectives of this in-vitro investigation were to examine the effect of midazolam on neutrophil p38 MAPK activation (phosphorylation) following in-vitro ischaemia-reperfusion injury, and the expression of adhesion molecule CD11b\\/CD18.

Stimulation of DNA synthesis in cultured rat alveolar type II cells

International Nuclear Information System (INIS)

Leslie, C.C.; McCormick-Shannon, K.; Robinson, P.C.; Mason, R.J.

1985-01-01

Restoration of the alveolar epithelium after injury is thought to be dependent on the proliferation of alveolar type II cells. To understand the factors that may be involved in promoting type II cell proliferation in vivo, we determined the effect of potential mitogens and culture substrata on DNA synthesis in rat alveolar type II cells in primary culture. Type II cells cultured in basal medium containing 10% fetal bovine serum (FBS) exhibited essentially no DNA synthesis. Factors that stimulated 3 H-thymidine incorporation included cholera toxin, epidermal growth factor, and rat serum. The greatest degree of stimulation was achieved by plating type II cells on an extracellular matrix prepared from bovine corneal endothelial cells and then by culturing the pneumocytes in medium containing rat serum, cholera toxin, insulin, and epidermal growth factor. Under conditions of stimulation of 3 H-thymidine incorporation there was an increased DNA content per culture dish but no increase in cell number. The ability of various culture conditions to promote DNA synthesis in type II cells was verified by autoradiography. Type II cells were identified by the presence of cytoplasmic inclusions, which were visualized by tannic acid staining before autoradiography. These results demonstrate the importance of soluble factors and culture substratum in stimulating DNA synthesis in rat alveolar type II cells in primary culture

p38 mitogen-activated protein kinase plays a key role in regulating MAPKAPK2 expression

International Nuclear Information System (INIS)

Sudo, Tatsuhiko; Kawai, Kayoko; Matsuzaki, Hiroshi; Osada, Hiroyuki

2005-01-01

One of three major families of the mitogen-activated kinases (MAPK), p38 as well as JNK, has been shown to transduce extracellular stress stimuli into cellular responses by phospho-relay cascades. Among p38 families, p38α is a widely characterized isoform and the biological phenomena are explained by its kinase activity regulating functions of its downstream substrates. However, its specific contributions to each phenomenon are yet not fully elucidated. For better understanding of the role of MAPKs, especially p38α, we utilized newly established mouse fibroblast cell lines originated from a p38α null mouse, namely, a parental cell line without p38α gene locus, knockout of p38α (KOP), Zeosin-resistant (ZKOP), revertant of p38α (RKOP), and Exip revertant (EKOP). EKOP is smaller in size but grows faster than the others. Although comparable amounts of ERK and JNK are expressed in each cell line, ERK is highly phosphorylated in EKOP even in normal culture conditions. Serum stimulation after serum starvation led to ERK phosphorylation in RKOP and ZKOP, but not in EKOP as much. On the contrary, relative phosphorylation level of JNK to total JNK in response to UV was low in RKOP. And its phosphorylation as well as total JNK is slightly lower in EKOP. RKOP is less sensitive to UV irradiation as judged by the survival rate. Stress response upon UV or sorbitol stimuli, leading to mitogen activate protein kinase activated kinase 2 (MAPKAPK2) phosphorylation, was only observed in RKOP. Further experiments reveal that MAPKAPK2 expression is largely suppressed in ZKOP and EKOP. Its expression was recovered by re-introduction of p38α. The loss of MAPKAPK2 expression accompanied by the defect of p38α is confirmed in an embryonic extract prepared from p38α null mice. These data demonstrate that p38 signal pathway is regulated not only by phosphorylation but also by modulation of the expression of its component. Together, we have established cell lines that can be used in

Nonspecific activation of murine lymphocytes. IV. Proliferation of a distinct, late maturing lymphocyte subpopulation induced by 2-mercaptoethanol

International Nuclear Information System (INIS)

Goodman, M.G.; Fidler, J.M.; Weigle, W.O.

1978-01-01

The lymphocyte subpopulations that are activated by 2-ME, LPS, poly IC, and PPD were studied in terms of their maturational characteristics. Attempts to stimulate hepatic and splenic lymphoid cells from mice of different ages with these mitogens demonstrated a well ordered sequence for the emergency of mitogen responsiveness in C3H mice: reactivity to LPS and Poly IC was observed early in maturation and was followed by that to PPD, and finally by the development of responsiveness to 2-ME. The same sequence appeared when the mitogen responsiveness of lethally irradiated, fetal liver-reconstituted syngeneic adult recipients was examined. The mitogenic action of 2-ME was dissociated from its ability to enhance lymphocyte reactivity to other mitogens in mice too young to respond to 2-ME as a mitogen. Experiments in which additivity of responses was assayed by adding mitogens to culture singly or conjointly indicated that LPS and Poly IC activate nearly identical B lymphocyte subpopulations, whereas PPD stimulates a subset of cells distinct from that which is responsive to the former two mitogens. The mitogen responsiveness of CBA/N mice, relative to normal CBA/WEHI mice, was shown to decrease as a function of the maturity of the subpopulation of lymphocytes activated. The CBA/N mouse was shown to be unresponsive to stimulation by 2-ME

SNT-2 interacts with ERK2 and negatively regulates ERK2 signaling in response to EGF stimulation

International Nuclear Information System (INIS)

Huang Lin; Gotoh, Noriko; Zhang Shengliang; Shibuya, Masabumi; Yamamoto, Tadashi; Tsuchida, Nobuo

2004-01-01

The control of cellular responses with fibroblast growth factors and neurotrophins is mediated through membrane-linked docking proteins, SNT (suc1-binding neurotrophic target)-1/FRS2α and SNT-2/FRS2β. ERK1/2 are members of the mitogen-activated protein kinase family that regulate diverse cellular activities in response to various stimuli. Here, we demonstrate that SNT-2 does not become tyrosine phosphorylated significantly in response to EGF but forms a complex with ERK2 via the region of 186-252 amino acid residues, and the complex formation is enhanced upon EGF stimulation. SNT-2 downregulates ERK2 phosphorylation, suppresses and delays ERK2 nuclear accumulation which occurs following EGF stimulation. In contrast, the mutant SNT-2 which carries deletion of 186-252 amino acids and lacks ERK2 binding does not have these effects. These observations suggest that SNT-2 negatively regulates ERK2 signaling activated via EGF stimulation through direct binding to ERK2

The down-regulation of the mitogenic fibrinogen receptor (MFR) in serum-containing medium does not occur in defined medium.

Science.gov (United States)

Levesque, J P; Hatzfeld, A; Domart, I; Hatzfeld, J

1990-02-01

Normal human hemopoietic cells such as early bone marrow progenitors, or lymphoma-derived cell lines such as Raji or JM cells, possess a low-affinity receptor specific for fibrinogen. This receptor triggers a mitogenic effect. It differs from the glycoprotein IIb-IIIa which is involved in fibrinogen-induced platelet aggregation. We demonstrate here that this mitogenic fibrinogen receptor (MFR) can be internalized or reexpressed, depending on culture conditions. Internalization was temperature-dependent. At 37 degrees C in the presence of cycloheximide or actinomycin D, the half-life of cell surface MFRs was 2 h, independent of receptor occupancy. Binding of fibrinogen to the MFR resulted in a down-regulation which was fibrinogen dose-dependent. This occurred in serum-supplemented medium but not in defined medium supplemented with fatty acids. Reexpression of MFRs could be induced in 28 to 42 h by serum removal. The down-regulation of mitogenic receptors in plasma or serum could explain why normal cells do not proliferate in the peripheral blood.

Multi Channels PWM Controller for Thermoelectric Cooler Using a Programmable Logic Device and Lab-Windows CVI

Directory of Open Access Journals (Sweden)

Eli FLAXER

2008-09-01

Full Text Available We present a complete design of a multi channels PID controller for Thermoelectric Cooler (TEC using a pulse width modulation (PWM technique implemented by a dedicated programmable logic device (PLD programmed by VHDL. The PID control loop is implemented by software written by National Instrument Lab-Windows CVI. Due to the fact that the implementation is by a VHDL and PLD the design is modular, as a result, the circuit is very compact in size and very low cost as compared to any commercial product. In addition, since the control loop is implemented by software running on a personal computer (PC using a C language, it is easy to adjust the controller to various environmental conditions and for a width range of sensors like: a thermo couple (TC, thermistor, resistance temperature detectors (RTD etc. We demonstrate the performance of this circuit as a controller for a small incubator using thermistor as the temperature sensor.

Regulation of brain capillary endothelial cells by P2Y receptors coupled to Ca2+, phospholipase C and mitogen-activated protein kinase.

Science.gov (United States)

Albert, J L; Boyle, J P; Roberts, J A; Challiss, R A; Gubby, S E; Boarder, M R

1997-11-01

1. The blood-brain barrier is formed by capillary endothelial cells and is regulated by cell-surface receptors, such as the G protein-coupled P2Y receptors for nucleotides. Here we investigated some of the characteristics of control of brain endothelial cells by these receptors, characterizing the phospholipase C and Ca2+ response and investigating the possible involvement of mitogen-activated protein kinases (MAPK). 2. Using an unpassaged primary culture of rat brain capillary endothelial cells we showed that ATP, UTP and 2-methylthio ATP (2MeSATP) give similar and substantial increases in cytosolic Ca2+, with a rapid rise to peak followed by a slower decline towards basal or to a sustained plateau. Removal of extracellular Ca2+ had little effect on the peak Ca2+-response, but resulted in a more rapid decline to basal. There was no response to alpha,beta-MethylATP (alpha,beta MeATP) in these unpassaged cells, but a response to this P2X agonist was seen after a single passage. 3. ATP (log EC50 -5.1+/-0.2) also caused an increase in the total [3H]-inositol (poly)phosphates ([3H]-InsPx) in the presence of lithium with a rank order of agonist potency of ATP=UTP=UDP>ADP, with 2MeSATP and alpha,beta MeATP giving no detectable response. 4. Stimulating the cells with ATP or UTP gave a rapid rise in the level of inositol 1,4,5-trisphosphate (Ins(1,4,5)P3), with a peak at 10 s followed by a decline to a sustained plateau phase. 2MeSATP gave no detectable increase in the level of Ins(1,4,5)P3. 5. None of the nucleotides tested affected basal cyclic AMP, while ATP and ATPgammaS, but not 2MeSATP, stimulated cyclic AMP levels in the presence of 5 microM forskolin. 6. Both UTP and ATP stimulated tyrosine phosphorylation of p42 and p44 mitogen-activated protein kinase (MAPK), while 2MeSATP gave a smaller increase in this index of MAPK activation. By use of a peptide kinase assay, UTP gave a substantial increase in MAPK activity with a concentration-dependency consistent with

Sensitivity of cultured lymphocytes from patients with nevoid basal cell carcinoma syndrome to ultraviolet light and phytohemagglutinin stimulation

International Nuclear Information System (INIS)

Ferraro, P.; Celotti, L.; Furlan, D.; Pattarello, I.; Peserico, A.

1990-01-01

DNA repair and replication after in vitro UV irradiation were determined in cultured peripheral blood lymphocytes from 6 patients with nevoid basal cell carcinoma syndrome (NBCCS) and from a group of control donors. DNA repair synthesis (UDS) was measured in unstimulated lymphocytes by incubation with 3H-TdR in the presence of hydroxyurea for 3 and 6 h after UV irradiation (6-48 J/m2). DNA replication was measured in PHA-stimulated lymphocytes, UV-irradiated or mock-irradiated, by incubation with 3H-TdR for 24 h. The effect of the mitogen was followed during 5 days after stimulation by determining the incorporation of 3H-TdR, the increase of cell number, and the mitotic index. NBCCS and control lymphocytes showed equal sensitivity to UV light in terms of UDS and reduced response to PHA. On the contrary, the mitotic index and the number of cells in stimulated cultures were significantly lower in the affected subjects. These data suggest an altered progression along the cell cycle, which could be characteristic of stimulated NBCCS lymphocytes

Hypoxia-induced mitogenic factor enhances angiogenesis by promoting proliferation and migration of endothelial cells

International Nuclear Information System (INIS)

Tong Qiangsong; Zheng Liduan; Li Bo; Wang Danming; Huang Chuanshu; Matuschak, George M.; Li Dechun

2006-01-01

Our previous studies have indicated that hypoxia-induced mitogenic factor (HIMF) has angiogenic properties in an in vivo matrigel plug model and HIMF upregulates expression of vascular endothelial growth factor (VEGF) in mouse lungs and cultured lung epithelial cells. However, whether HIMF exerts angiogenic effects through modulating endothelial cell function remains unknown. In this study, mouse aortic rings cultured with recombinant HIMF protein resulted in enhanced vascular sprouting and increased endothelial cell spreading as confirmed by Dil-Ac-LDL uptake, von Willebrand factor and CD31 staining. In cultured mouse endothelial cell line SVEC 4-10, HIMF dose-dependently enhanced cell proliferation, in vitro migration and tubulogenesis, which was not attenuated by SU1498, a VEGFR2/Flk-1 receptor tyrosine kinase inhibitor. Moreover, HIMF stimulation resulted in phosphorylation of Akt, p38 and ERK1/2 kinases in SVEC 4-10 cells. Treatment of mouse aortic rings and SVEC 4-10 cells with LY294002, but not SB203580, PD098059 or U0126, abolished HIMF-induced vascular sprouting and angiogenic responses. In addition, transfection of a dominant-negative mutant of phosphatidylinositol 3-kinase (PI-3K), Δp85, blocked HIMF-induced phosphorylation of Akt, endothelial activation and tubulogenesis. These results indicate that HIMF enhances angiogenesis by promoting proliferation and migration of endothelial cells via activation of the PI-3K/Akt pathways

DSP30 and interleukin-2 as a mitotic stimulant in B-cell disorders including those with a low disease burden.

Science.gov (United States)

Dun, Karen A; Riley, Louise A; Diano, Giuseppe; Adams, Leanne B; Chiu, Eleanor; Sharma, Archna

2018-05-01

Chromosome abnormalities detected during cytogenetic investigations for B-cell malignancy offer prognostic information that can have wide ranging clinical impacts on patients. These impacts may include monitoring frequency, treatment type, and disease staging level. The use of the synthetic oligonucleotide DSP30 combined with interleukin 2 (IL2) has been described as an effective mitotic stimulant in B-cell disorders, not only in chronic lymphocytic leukemia (CLL) but also in a range of other B-cell malignancies. Here, we describe the comparison of two B-cell mitogens, lipopolysaccharide (LPS), and DSP30 combined with IL2 as mitogens in a range of common B-cell disorders excluding CLL. The results showed that DSP30/IL2 was an effective mitogen in mature B-cell disorders, revealing abnormal cytogenetic results in a range of B-cell malignancies. The abnormality rate increased when compared to the use of LPS to 64% (DSP30/IL2) from 14% (LPS). In a number of cases the disease burden was proportionally very low, less than 10% of white cells. In 37% of these cases, the DSP30 culture revealed abnormal results. Importantly, we also obtained abnormal conventional cytogenetics results in 3 bone marrow cases in which immunophenotyping showed an absence of an abnormal B-cell clone. In these cases, the cytogenetics results correlated with the provisional diagnosis and altered their staging level. The use of DSP30 and IL2 is recommended for use in many B-cell malignancies as an effective mitogen and their use has been shown to enable successful culture of the malignant clone, even at very low levels of disease. © 2018 Wiley Periodicals, Inc.

Impact of frequency modulation ratio on capacitor cells balancing in phase-shifted PWM based chain-link STATCOM

DEFF Research Database (Denmark)

Behrouzian, Ehsan; Bongiorno, Massimo; Teodorescu, Remus

2014-01-01

to provide more uniform power distribution among the cells, two different methods called, a) carrier swapping and b) non-integer frequency modulation ratio are studied. In particular, it is shown that the selection of a non-integer frequency modulation ratio helps in providing a more uniform power......The purpose of this paper is to investigate the impact of switching harmonics on the instantaneous power that flows in the cells of a chain-link based STATCOM when using Phase-Shifted PWM. Two different cases are investigated for the converter cells: low, and high switching frequency. It is shown...... that any deviation from the ideal conditions lead to undesired harmonics, which will impact the charge of the dc capacitors. It is also shown that for low switching frequencies, cells voltage sideband harmonics interact with baseband harmonics of the current and causes extra source of unbalance. In order...

Radiosensitivity of angiogenic and mitogenic factors in human amniotic membrane

International Nuclear Information System (INIS)

Deocaris, Custer C.; De Guzman, Zenaida M.; Deocaris, Chester C.; Jacinto, Sonia D.

2003-01-01

Amniotic membrane as a temporary biological dressing remains as a beneficial and cost-effective means of treating burns in developing countries. This medical application is attributed mainly to placental structural and biochemical features that are important for maintaining proper embryonic development. Since fresh amnions are nevertheless for straightforward clinical use and for preservation, radiation-sterilization is been performed to improve the safety of this placental material. However, like any other sterilization method, gamma-radiation may induce physical and chemical changes that may influence the biological property of the material. Thus, the aim of this study is to compare the effects of various levels of radiation-sterilization protocols for human amnions on angiogenic (neovascularization) and epithelial-mitogenic activities, both of which are physiological processes fundamental to wound healing. Water-soluble extract of non-irradiated amnions demonstrates a strong stimulatory effect on both cell proliferation and angiogenesis. No change in biological activity is seen in amnions irradiated at 25 kGy, the sterilization dose used by the Philippine Nuclear Research Institute (PNRI) for the production of radiation-sterilized human amniotic membranes (RSHAM). However, it appears that amniotic angiogenic factors are more radiosensitive than its mitogenic components, evident from the depressed vascularization of the chorioallantoic membrane (CAM) exposed to 35 kGy-irradiated amnions. The dose of 35 kGy is at present the medical sterilization dose used at the Central Tissue Bank in Warsaw (Poland) for the preparation of their amnion allografts. (Authors)

CLARITY-BPA: Effects of chronic bisphenol A exposure on the immune system: Part 2 - Characterization of lymphoproliferative and immune effector responses by splenic leukocytes.

Science.gov (United States)

Li, Jinpeng; Bach, Anthony; Crawford, Robert B; Phadnis-Moghe, Ashwini S; Chen, Weimin; D'Ingillo, Shawna; Kovalova, Natalia; Suarez-Martinez, Jose E; Zhou, Jiajun; Kaplan, Barbara L F; Kaminski, Norbert E

2018-03-01

Bisphenol A (BPA) is commonly used in the manufacturing of a wide range of consumer products, including polycarbonate plastics, epoxy resin that lines beverage and food cans, and some dental sealants. Consumption of food and beverages containing BPA represents the primary route of human BPA exposure, which is virtually ubiquitous. An increasing number of studies have evaluated the effects of BPA on immune responses in laboratory animals that have reported a variety of effects some of which have been contradictory. To address the divergent findings surrounding BPA exposure, a comprehensive chronic treatment study of BPA was conducted in Sprague-Dawley rats, termed the Consortium Linking Academic and Regulatory Insights on Toxicity of BPA (CLARITY-BPA). As a participant in the CLARITY-BPA project, our studies evaluated the effects of BPA on a broad range of immune function endpoints using spleen cells isolated from BPA or vehicle treated rats. This comprehensive assessment included measurements of lymphoproliferation in response to mitogenic stimuli, immunoglobulin production by B cells, and cellular activation of T cells, NK cells, monocytes, granulocytes, macrophages and dendritic cells. In total, 630 different measurements in BPA treated rats were performed of which 35 measurements were statistically different from vehicle controls. The most substantive alteration associated with BPA treatment was the augmentation of lymphoproliferation in response to pokeweed mitogen stimulations in 1 year old male rats, which was also observed in the reference estrogen ethinyl estradiol treated groups. With the exception of the aforementioned, the statistically significant changes associated with BPA treatment were mostly sporadic and not dose-dependent with only one out of five BPA dose groups showing a statistical difference. In addition, the observed BPA-associated alterations were mostly moderate in magnitude and showed no persistent trend over the one-year time period

B cell receptor accessory molecule CD79α: characterisation and expression analysis in a cartilaginous fish, the spiny dogfish (Squalus acanthias).

Science.gov (United States)

Li, Ronggai; Wang, Tiehui; Bird, Steve; Zou, Jun; Dooley, Helen; Secombes, Christopher J

2013-06-01

CD79α (also known as Igα) is a component of the B cell antigen receptor complex and plays an important role in B cell signalling. The CD79α protein is present on the surface of B cells throughout their life cycle, and is absent on all other healthy cells, making it a highly reliable marker for B cells in mammals. In this study the spiny dogfish (Squalus acanthias) CD79α (SaCD79α) is described and its expression studied under constitutive and stimulated conditions. The spiny dogfish CD79α cDNA contains an open reading frame of 618 bp, encoding a protein of 205 amino acids. Comparison of the SaCD79α gene with that of other species shows that the gross structure (number of exons, exon/intron boundaries, etc.) is highly conserved across phylogeny. Additionally, analysis of the 5' flanking region shows SaCD79α lacks a TATA box and possesses binding sites for multiple transcription factors implicated in its B cell-specific gene transcription in other species. Spiny dogfish CD79α is most highly expressed in immune tissues, such as spleen, epigonal and Leydig organ, and its transcript level significantly correlates with those of spiny dogfish immunoglobulin heavy chains. Additionally, CD79α transcription is up-regulated, to a small but significant degree, in peripheral blood cells following stimulation with pokeweed mitogen. These results strongly indicate that, as in mammals, spiny dogfish CD79α is expressed by shark B cells where it associates with surface-bound immunoglobulin to form a fully functional BCR, and thus may serve as a pan-B cell marker in future shark immunological studies. Copyright © 2013 Elsevier Ltd. All rights reserved.

Characterization of a human antigen specific helper factor

International Nuclear Information System (INIS)

Richardson, B.

1986-01-01

While antigen (Ag) specific helper factors have been characterized in mice, similar molecules have not been identified in humans. To characterize human antigen specific helper molecules, an IL-2 dependent tetanus toxoid (T.T.) reactive T cell line was fused with a 6-thioguanine resistant CEM line, and hybrids selected in medium containing hypoxanthine and azaserine. Hybrids were screened by culturing the cells with 35 S-Met then reacting the supernatants with T.T. or hepatitis vaccine immobilized on nitrocellulose. One hybrid, TT6BA-O, was identified which secreted a Met-containing molecule which bound T.T. but not hepatitis vaccine. Supernatants from TT6BA-O, but not the parent CEM line, when added to autologous peripheral blood mononuclear cells (PBMC's) stimulated secretion of T.T. specific antibodies (Abs). Specificity controls demonstrated that TT6BA-O supernatant did not induce antibodies to diphtheria toxoid, hepatitis vaccine or pneumococcal polysaccharide, and total immunoglobulin (lg) synthesis was minimally increased. In contrast, pokeweed mitogen stimulated significant lg synthesis as well as Ab's to pneumococcal polysaccharide and T.T. TT6BA-O supernatant induced anti-T.T.Ab's in autologous PBMC's but not PBMC's from 3 unrelated donors, suggesting that the activity of the helper factor is restricted, possibly by the MHC. The molecular weight of the helper factor was estimated at 100,000-150,000 by Sephacryl S-300 chromatography. Finally, the helper factor could be demonstrated to bind and elute from sephorose-immobilized T.T. and anti-DR antisera, but not anti-lg antisera or the T40/25 monoclonal antibody, which binds a nonpolymorphic determinant on the human T cell receptor. These results demonstrate that human Ag specific helper factors exist, bind antigen and bear class II MHC determinants

Regulation of mitogen-activated protein kinase 3/1 activity during meiosis resumption in mammals

Czech Academy of Sciences Publication Activity Database

Procházka, Radek; Blaha, Milan

2015-01-01

Roč. 61, č. 6 (2015), s. 495-502 ISSN 0916-8818 R&D Projects: GA MZe(CZ) QJ1510138 Institutional support: RVO:67985904 Keywords : cumulus oocyte complexes * meiosis resumption * mitogen-activated protein kinase 3/1 (MAPK3/1) Subject RIV: GI - Animal Husbandry ; Breeding Impact factor: 1.453, year: 2015

Newly Identified TLR9 Stimulant, M6-395 Is a Potent Polyclonal Activator for Murine B Cells.

Science.gov (United States)

Park, Mi-Hee; Jung, Yu-Jin; Kim, Pyeung-Hyeun

2012-02-01

Toll-like receptors (TLRs) have been extensively studied in recent years. However, functions of these molecules in murine B cell biology are largely unknown. A TLR4 stimulant, LPS is well known as a powerful polyclonal activator for murine B cells. In this study, we explored the effect of a murine TLR9 stimulant, M6-395 (a synthetic CpG ODNs) on B cell proliferation and Ig production. First, M6-395 was much more potent than LPS in augmenting B cell proliferation. As for Ig expression, M6-395 facilitated the expression of both TGF-β1-induced germ line transcript α (GLTα) and IL-4-induced GLTγ1 as levels as those by LPS and Pam3CSK4 (TLR1/2 agonist) : a certain Ig GLT expression is regarded as an indicative of the corresponding isotype switching recombination. However, IgA and IgG1 secretion patterns were quite different--these Ig isotype secretions by M6-395 were much less than those by LPS and Pam3CSK4. Moreover, the increase of IgA and IgG1 production by LPS and Pam3CSK4 was virtually abrogated by M6-395. The same was true for the secretion of IgG3. We found that this unexpected phenomena provoked by M6-395 is attributed, at least in part, to its excessive mitogenic nature. Taken together, these results suggest that M6-395 can act as a murine polyclonal activator but its strong mitogenic activity is unfavorable to Ig isotype switching.

IRS-1: essential for insulin- and IL-4-stimulated mitogenesis in hematopoietic cells.

Science.gov (United States)

Wang, L M; Myers, M G; Sun, X J; Aaronson, S A; White, M; Pierce, J H

1993-09-17

Although several interleukin-3 (IL-3)-dependent cell lines proliferate in response to IL-4 or insulin, the 32D line does not. Insulin and IL-4 sensitivity was restored to 32D cells by expression of IRS-1, the principal substrate of the insulin receptor. Although 32D cells possessed receptors for both factors, they lacked the IRS-1--related protein, 4PS, which becomes phosphorylated by tyrosine in insulin- or IL-4--responsive lines after stimulation. These results indicate that factors that bind unrelated receptors can use similar mitogenic signaling pathways in hematopoietic cells and that 4PS and IRS-1 are functionally similar proteins that are essential for insulin- and IL-4--induced proliferation.

PSM/SH2-B distributes selected mitogenic receptor signals to distinct components in the PI3-kinase and MAP kinase signaling pathways.

Science.gov (United States)

Deng, Youping; Xu, Hu; Riedel, Heimo

2007-02-15

The Pro-rich, PH, and SH2 domain containing mitogenic signaling adapter PSM/SH2-B has been implicated as a cellular partner of various mitogenic receptor tyrosine kinases and related signaling mechanisms. Here, we report in a direct comparison of three peptide hormones, that PSM participates in the assembly of distinct mitogenic signaling complexes in response to insulin or IGF-I when compared to PDGF in cultured normal fibroblasts. The complex formed in response to insulin or IGF-I involves the respective peptide hormone receptor and presumably the established components leading to MAP kinase activation. However, our data suggest an alternative link from the PDGF receptor via PSM directly to MEK1/2 and consequently also to p44/42 activation, possibly through a scaffold protein. At least two PSM domains participate, the SH2 domain anticipated to link PSM to the respective receptor and the Pro-rich region in an association with an unidentified downstream component resulting in direct MEK1/2 and p44/42 regulation. The PDGF receptor signaling complex formed in response to PDGF involves PI 3-kinase in addition to the same components and interactions as described for insulin or IGF-I. PSM associates with PI 3-kinase via p85 and in addition the PSM PH domain participates in the regulation of PI 3-kinase activity, presumably through membrane interaction. In contrast, the PSM Pro-rich region appears to participate only in the MAP kinase signal. Both pathways contribute to the mitogenic response as shown by cell proliferation, survival, and focus formation. PSM regulates p38 MAP kinase activity in a pathway unrelated to the mitogenic response.

Cancer Cell-derived Exosomes Induce Mitogen-activated Protein Kinase-dependent Monocyte Survival by Transport of Functional Receptor Tyrosine Kinases*

Science.gov (United States)

Song, Xiao; Ding, Yanping; Liu, Gang; Yang, Xiao; Zhao, Ruifang; Zhang, Yinlong; Zhao, Xiao; Anderson, Gregory J.; Nie, Guangjun

2016-01-01

Tumor-associated macrophages (TAM) play pivotal roles in cancer initiation and progression. Monocytes, the precursors of TAMs, normally undergo spontaneous apoptosis within 2 days, but can subsist in the inflammatory tumor microenvironment for continuous survival and generation of sufficient TAMs. The mechanisms underlying tumor-driving monocyte survival remain obscure. Here we report that cancer cell-derived exosomes were crucial mediators for monocyte survival in the inflammatory niche. Analysis of the survival-promoting molecules in monocytes revealed that cancer cell-derived exosomes activated Ras and extracellular signal-regulated kinases in the mitogen-activated protein kinase (MAPK) pathway, resulting in the prevention of caspase cleavage. Phosphorylated receptor tyrosine kinases (RTKs), such as phosphorylated epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER-2), were abundantly expressed in cancer cell-derived exosomes. Knock-out of EGFR or/and HER-2, or alternatively, inhibitors against their phosphorylation significantly disturbed the exosome-mediated activation of the MAPK pathway, inhibition of caspase cleavage, and increase in survival rate in monocytes. Moreover, the deprived survival-stimulating activity of exosomes due to null expression of EGFR and HER-2 could be restored by activation of another RTK, insulin receptor. Overall, our study uncovered a mechanism of tumor-associated monocyte survival and demonstrated that cancer cell-derived exosomes can stimulate the MAPK pathway in monocytes through transport of functional RTKs, leading to inactivation of apoptosis-related caspases. This work provides insights into the long sought question on monocyte survival prior to formation of plentiful TAMs in the tumor microenvironment. PMID:26895960

Olfactometer for functional resonance imaging

International Nuclear Information System (INIS)

Andrieu, Patrice

2013-01-01

The Magnetic Resonance Imaging (fMRI) has been developing for twenty years. Indeed, the marketing of high-resolution MRI (5 Tesla and 7 Tesla recently) allowed the study of brain mechanisms. The research work of this PHD was to develop instrumentation for objective studies of brain behavior during a sensory stimulation. We are interested in the study of olfaction. We have designed and built a six-channel olfactometer, synchronized with breathing and controlled by computer. The originality of our work lies in the modularity of our device, which makes it adaptable to a wide range of studies. We also propose a new method to change the intensity of stimulation delivered: the Pulse Width Modulation (PWM). This device has been used in several studies in fMRI. The effectiveness of the PWM is highlighted in a psychophysical study described in this manuscript. (author)

Diseño asistido por computadora del patrón de encendido en inversores de tensión, utilizando la técnica de control PWM

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Elio Castro Alfonso

2011-03-01

Full Text Available El artículo se relaciona con el desarrollo de un programa de ayuda para el diseño de los patrones de control deinversores de potencia tipo puente que utilizan técnicas PWM (Pulse Width Modulation. Este método de controlbien establecido, permite incorporar todas las funciones del inversor, pero en lo fundamental garantizar la regulaciónde la tensión de salida manteniendo el factor de distorsión de armónicos lo suficientemente bajo (3-5 % comopara ser tolerado por los consumidores usuales. Obtener un adecuado diseño del patrón de tablas de búsquedapara su utilización en un inversor real empleando microcontrolador, es el problema fundamental a resolver. Losresultados del trabajo han sido comprobados con la ayuda de un procesador 8031.  This paper is related with a program which calculates the control pattern of single-phase power inverters usingPWM techniques.This kind of control if it's well established makes possible to incorporate not all the inverterfunctions,but mainly the voltage regulation by keeping the total harmonics distorsion as low as possible (3-5%;quite good for any consumer.The main problem to solve is to get a proper design of the tables search pattern tobe used in a real single-phase inverter control using any processor.The experimental work has been done usingthe 8031 microcontroller.

The COP9 signalosome converts temporal hormone signaling to spatial restriction on neural competence.

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Yi-Chun Huang

2014-11-01

Full Text Available During development, neural competence is conferred and maintained by integrating spatial and temporal regulations. The Drosophila sensory bristles that detect mechanical and chemical stimulations are arranged in stereotypical positions. The anterior wing margin (AWM is arrayed with neuron-innervated sensory bristles, while posterior wing margin (PWM bristles are non-innervated. We found that the COP9 signalosome (CSN suppresses the neural competence of non-innervated bristles at the PWM. In CSN mutants, PWM bristles are transformed into neuron-innervated, which is attributed to sustained expression of the neural-determining factor Senseless (Sens. The CSN suppresses Sens through repression of the ecdysone signaling target gene broad (br that encodes the BR-Z1 transcription factor to activate sens expression. Strikingly, CSN suppression of BR-Z1 is initiated at the prepupa-to-pupa transition, leading to Sens downregulation, and termination of the neural competence of PWM bristles. The role of ecdysone signaling to repress br after the prepupa-to-pupa transition is distinct from its conventional role in activation, and requires CSN deneddylating activity and multiple cullins, the major substrates of deneddylation. Several CSN subunits physically associate with ecdysone receptors to represses br at the transcriptional level. We propose a model in which nuclear hormone receptors cooperate with the deneddylation machinery to temporally shutdown downstream target gene expression, conferring a spatial restriction on neural competence at the PWM.

Mitogen-activated protein kinase 1 from disk abalone (Haliotis discus discus): Roles in early development and immunity-related transcriptional responses.

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Perera, N C N; Godahewa, G I; Lee, Jehee

2016-12-01

Mitogen-activated protein kinase (MAPK) is involved in the regulation of cellular events by mediating signal transduction pathways. MAPK1 is a member of the extracellular-signal regulated kinases (ERKs), playing roles in cell proliferation, differentiation, and development. This is mainly in response to growth factors, mitogens, and many environmental stresses. In the current study, we have characterized the structural features of a homolog of MAPK1 from disk abalone (AbMAPK1). Further, we have unraveled its expressional kinetics against different experimental pathogenic infections or related chemical stimulants. AbMAPK1 harbors a 5' untranslated region (UTR) of 23 bps, a coding sequence of 1104 bps, and a 3' UTR of 448 bp. The putative peptide comprises a predicted molecular mass of 42.2 kDa, with a theoretical pI of 6.28. Based on the in silico analysis, AbMAPK1 possesses two N-glycosylation sites, one S_TK catalytic domain, and a conserved His-Arg-Asp domain (HRD). In addition, a conservative glycine rich ATP-phosphate-binding loop and a threonine-x-tyrosine motif (TEY) important for the autophosphorylation were also identified in the protein. Homology assessment of AbMAPK1 showed several conserved regions, and ark clam (Aplysia californica) showed the highest sequence identity (87.9%). The phylogenetic analysis supported close evolutionary kinship with molluscan orthologs. Constitutive expression of AbMAPK1 was observed in six different tissues of disk abalone, with the highest expression in the digestive tract, followed by the gills and hemocytes. Highest AbMAPK1 mRNA expression level was detected at the trochophore developmental stage, suggesting its role in abalone cell differentiation and proliferation. Significant modulation of AbMAPK1 expression under pathogenic stress suggested its putative involvement in the immune defense mechanism. Copyright © 2016 Elsevier Ltd. All rights reserved.

PV Power-Generation System with a Phase-Shift PWM Technique for High Step-Up Voltage Applications

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Cheng-Tao Tsai

2012-01-01

Full Text Available A PV power-generation system with a phase-shift pulse-width modulation (PWM technique for high step-up voltage applications is proposed. The proposed power-generation system consists of two stages. In the input stage, all power switches of the full-bridge converter with phase-shift technique can be operated with zero-current switching (ZCS at turn-on or turn-off transition. Hence, the switching losses of the power switches can be reduced. Then, in the DC output stage, a voltage-doubler circuit is used to boost a high dc-link bus voltage. To supply a utility power, a dc/ac inverter is connected to induce a sinusoidal source. In order to draw a maximum power from PV arrays source, a microcontroller is incorporated with the perturbation and observation method to implement maximum power point tracking (MPPT algorithm and power regulating scheme. In this study, a full load power of 300 W prototype has been built. Experimental results are presented to verify the performance and feasibility of the proposed PV power-generation system.

Anti-inflammatory compound resveratrol suppresses homocysteine formation in stimulated human peripheral blood mononuclear cells in vitro.

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Schroecksnadel, Katharina; Winkler, Christiana; Wirleitner, Barbara; Schennach, Harald; Weiss, Günter; Fuchs, Dietmar

2005-01-01

Inflammation, immune activation and oxidative stress play a major role in the pathogenesis of cardiovascular disorders. In addition to markers of inflammation, moderate hyperhomocysteinemia is an independent risk factor for cardiovascular disease, and there is a link between the activation of immunocompetent cells and the enhanced formation of homocysteine in vitro. Likewise, anti-inflammatory drugs and nutrients rich in antioxidant vitamins are able to reduce cardiovascular risk and to slow down the atherogenic process. Resveratrol, a phenolic antioxidant synthesized in grapes and vegetables and present in wine, has also been supposed to be beneficial for the prevention of cardiovascular events. Apart from its strong antioxidant properties, resveratrol has also been demonstrated to act as an anti-inflammatory agent. In this study the influence of resveratrol on the production of homocysteine by stimulated human peripheral blood mononuclear cells (PBMCs) was investigated. Results were compared to earlier described effects of the anti-inflammatory compounds aspirin and salicylic acid and of the lipid-lowering drug atorvastatin. Stimulation of PBMCs with the mitogens concanavalin A and phytohemagglutinin induced significantly higher homocysteine accumulation in supernatants compared with unstimulated cells. Treatment with 10-100 muM resveratrol suppressed homocysteine formation in a dose-dependent manner. Resveratrol did not influence the release of homocysteine from resting PBMCs. The data suggest that resveratrol may prevent homocysteine accumulation in the blood by suppressing immune activation cascades and the proliferation of mitogen-driven T-cells. The effect of resveratrol to down-regulate the release of homo-cysteine was comparable to the decline of neopterin concentrations in the same experiments. The suppressive effect of resveratrol was very similar to results obtained earlier with aspirin, salicylic acid and atorvastatin; however, it appeared that doses

Effect of ultra violet irradiation on the interplay between Th1 and Th2 lymphocytes

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Salma Y Abo Elnazar

2015-03-01

Full Text Available Although UV radiation is used to treat several diseases, including rickets, psoriasis, eczema and jaundice, prolonged human exposure to UV radiation may result in acute and chronic health effects on the skin, eye and immune system. Aim: this study is carried out to show the effect of UV on both splenocyte lymphoproliferative response and their capacity to produce IL-12 and IL-10 in mice. Methods: mice were exposed to whole body UVB and tested for the effect of recovery times on splenocyte proliferation and cytokine production. In addition, direct irradiation of spleens and lymphocyte suspension was done. Basal and mitogen-stimulated splenocyte proliferation was assessed by MTT assay while IL-10 and IL-12 were measured using ELISA. Results showed significant suppression in splenocyte proliferation in comparison with control. IL-12 levels were significantly reduced while IL-10 was increased. ConA and PWM had no significant changes in IL-10 while Con A caused a highly significant increase in IL-12 at day six recovery in UVB body irradiation. Conclusion: Exposure to UVB radiation could cause a state of immune suppression and shifts Th1/Th2 cell response. This effect is closely associated with the reduction of Th1 cytokines' expression and increase in Th2 cytokines' levels.

Differential expression of insulin like growth factor I and other fibroblast mitogens in porcine colostrum and milk

International Nuclear Information System (INIS)

Tan, T.J.; Simmen, R.C.M.; Simmen, F.A.

1987-01-01

Sow mammary secretions contain at least 3 distinct growth factor activities, distinguished by their size and relative abundance in colostrum or later milk. Gel filtration of colostrum in Sephadex G-200 columns, followed by acid-ethanol extraction and radioimmunoassay (RIA) for insulin like growth factor I (IGF-I) revealed high levels of this factor in the 150K and 50K MW regions, characteristic of IGF-I: binding protein complexes. Acid treatment of these fractions yielded free IGF-I peptide (7.5K). Parallel mitogen assays with a fibroblast cell line (AKR-2B) demonstrated a predominant peak of high MW activity (sow colostral growth factor-I, SCGF-I) eluting near the column void volume (MW > 150K). Treatment of SCGF-I with 1M acetic acid resulted in a size reduction of the mitogenic activity (MW < 10K), suggesting association of SCGF-I with a binding protein. The SCGF-I peptide was noncompetitive in IGF-I RIA, was distinct in MW from free IGF-I, and was not mitogenic for chick embryo fibroblasts. Sow milk contains less IGF-I and SCGF-I but does display a predominant peak of small MW (∼ 3K) AKR-2B activity. The changes in expression of these growth factors during lactation may reflect differing roles in lactogenesis and/or neonatal growth and development

Immunomodulation and disease resistance in postyearling rainbow trout infected with Myxobolus cerebralis, the causative agent of whirling disease

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Densmore, Christine L.; Ottinger, C.A.; Blazer, V.S.; Iwanowicz, L.R.; Smith, D.R.

2004-01-01

Myxobolus cerebralis, the myxosporean parasite that causes whirling disease, has a number of deleterious effects on its salmonid host. Although it is well established that juvenile salmonids in the active stages of whirling disease mount an immune response to the pathogen, the occurrence and longevity of any related immunomodulatory effects are unknown. In this study, postyearling rainbow trout Oncorhynchus mykiss infected with M. cerebralis were examined for leukocyte functions and for resistance to Yersinia ruckeri, a bacterial pathogen of salmonids. Compared with uninfected controls, M. cerebralis-infected fish showed lower proliferative lymphocyte responses to four mitogens (concanavalin A, pokeweed mitogen, phytohemagglutinin, and lipopolysaccharide). Conversely, M. cerebralis-infected fish displayed greater bactericidal activity of anterior kidney macrophages than did uninfected fish. After bath challenges with K. ruckeri, M. cerebralis-infected fish had slightly lower survival and a more rapid onset of mortality than did the control fish. Renal tissue and fecal samples from M. cerebralis-infected and uninfected survivors were cultured for the presence of K. ruckeri, and no difference in prevalence was noted between the two groups. Because immunomodulatory changes in the M. cerebralis-infected fish involved functional enhancement and suppression of different leukocyte populations, disease resistance among M. cerebralis-infected fish in the later stages of whirling disease will probably vary with the secondary pathogen and the nature of immune response the pathogen evokes.

Enhancing effects of thymopoietin and T cell growth factor on mitogenic responsiveness and colony formation of lymphocytes from patients with preleukemia

International Nuclear Information System (INIS)

Knox, S.J.; Greenberg, B.R.; Anderson, R.W.; Shifrine, M.

1983-01-01

Cloning efficiencies and mitogenic responsiveness of lymphocytes from patients with preleukemic disorders are significantly depressed compared to normal values. TP-5 and IL-2 markedly increased the cloning efficiency and mitogenic responsiveness of lymphocytes from many of the preleukemic patients studied, while there was little or no effect in control cultures. Enhancement of lymphocyte responsiveness with TP-5 and IL-2 suggests the presence of maturational/-functional defects in these patients which may be compensated for in part by addition of TP-5 and IL-2

Systems biology analysis of mitogen activated protein kinase inhibitor resistance in malignant melanoma.

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Zecena, Helma; Tveit, Daniel; Wang, Zi; Farhat, Ahmed; Panchal, Parvita; Liu, Jing; Singh, Simar J; Sanghera, Amandeep; Bainiwal, Ajay; Teo, Shuan Y; Meyskens, Frank L; Liu-Smith, Feng; Filipp, Fabian V

2018-04-04

Kinase inhibition in the mitogen activated protein kinase (MAPK) pathway is a standard therapy for cancer patients with activating BRAF mutations. However, the anti-tumorigenic effect and clinical benefit are only transient, and tumors are prone to treatment resistance and relapse. To elucidate mechanistic insights into drug resistance, we have established an in vitro cellular model of MAPK inhibitor resistance in malignant melanoma. The cellular model evolved in response to clinical dosage of the BRAF inhibitor, vemurafenib, PLX4032. We conducted transcriptomic expression profiling using RNA-Seq and RT-qPCR arrays. Pathways of melanogenesis, MAPK signaling, cell cycle, and metabolism were significantly enriched among the set of differentially expressed genes of vemurafenib-resistant cells vs control. The underlying mechanism of treatment resistance and pathway rewiring was uncovered to be based on non-genomic adaptation and validated in two distinct melanoma models, SK-MEL-28 and A375. Both cell lines have activating BRAF mutations and display metastatic potential. Downregulation of dual specific phosphatases, tumor suppressors, and negative MAPK regulators reengages mitogenic signaling. Upregulation of growth factors, cytokines, and cognate receptors triggers signaling pathways circumventing BRAF blockage. Further, changes in amino acid and one-carbon metabolism support cellular proliferation despite MAPK inhibitor treatment. In addition, treatment-resistant cells upregulate pigmentation and melanogenesis, pathways which partially overlap with MAPK signaling. Upstream regulator analysis discovered significant perturbation in oncogenic forkhead box and hypoxia inducible factor family transcription factors. The established cellular models offer mechanistic insight into cellular changes and therapeutic targets under inhibitor resistance in malignant melanoma. At a systems biology level, the MAPK pathway undergoes major rewiring while acquiring inhibitor resistance

Treatment of intractable rheumatoid arthritis with total lymphoid irradiation

International Nuclear Information System (INIS)

Kotzin, B.L.; Strober, S.; Engleman, E.G.; Calin, A.; Hoppe, R.T.; Kansas, G.S.; Terrell, C.P.; Kaplan, H.S.

1981-01-01

Eleven patients with intractable rheumatoid arthritis were treated with total lymphoid irradiation (total dose, 2000 rad) in an uncontrolled feasibility study, as an alternative to long-term therapy with cytotoxic drugs such as cyclophosphamide and azathioprine. During a follow-up period of five to 18 months after total lymphoid irradiation, there was a profound and sustained suppression of the absolute lymphocyte count and in vitro lymphocyte function, as well as an increase in the ratio of Leu-2 (suppressor/cytotoxic) to Leu-3 (helper) T cells in the blood. Persistent circulating suppressor cells of the mixed leukocyte response and of pokeweed mitogen-induced immunoglobulin secretion developed in most patients. In nine of the 11 patients, these changes in immune status were associated with relief of joint tenderness and swelling and with improvement in function scores. Maximum improvement occurred approximately six months after irradiation and continued for the remainder of the observation period. Few severe or chronic side effects were associated with the radiotherapy

p75 Neurotrophin Receptor Signaling Activates Sterol Regulatory Element-binding Protein-2 in Hepatocyte Cells via p38 Mitogen-activated Protein Kinase and Caspase-3.

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Pham, Dan Duc; Do, Hai Thi; Bruelle, Céline; Kukkonen, Jyrki P; Eriksson, Ove; Mogollón, Isabel; Korhonen, Laura T; Arumäe, Urmas; Lindholm, Dan

2016-05-13

Nerve growth factor (NGF) influences the survival and differentiation of a specific population of neurons during development, but its role in non-neuronal cells has been less studied. We observed here that NGF and its pro-form, pro-NGF, are elevated in fatty livers from leptin-deficient mice compared with controls, concomitant with an increase in low density lipoprotein receptors (LDLRs). Stimulation of mouse primary hepatocytes with NGF or pro-NGF increased LDLR expression through the p75 neurotrophin receptor (p75NTR). Studies using Huh7 human hepatocyte cells showed that the neurotrophins activate the sterol regulatory element-binding protein-2 (SREBP2) that regulates genes involved in lipid metabolism. The mechanisms for this were related to stimulation of p38 mitogen-activated protein kinase (p38 MAPK) and activation of caspase-3 and SREBP2 cleavage following NGF and pro-NGF stimulations. Cell fractionation experiments showed that caspase-3 activity was increased particularly in the membrane fraction that harbors SREBP2 and caspase-2. Experiments showed further that caspase-2 interacts with pro-caspase-3 and that p38 MAPK reduced this interaction and caused caspase-3 activation. Because of the increased caspase-3 activity, the cells did not undergo cell death following p75NTR stimulation, possibly due to concomitant activation of nuclear factor-κB (NF-κB) pathway by the neurotrophins. These results identify a novel signaling pathway triggered by ligand-activated p75NTR that via p38 MAPK and caspase-3 mediate the activation of SREBP2. This pathway may regulate LDLRs and lipid uptake particularly after injury or during tissue inflammation accompanied by an increased production of growth factors, including NGF and pro-NGF. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Nicotine as a mitogenic stimulus for pancreatic acinar cell proliferation

Institute of Scientific and Technical Information of China (English)

Parimal Chowdhury; Kodetthoor B Udupa

2006-01-01

Cell proliferation is an important process in life for growth of normal and cancer cells. The signal transduction pathways activated during this process are strictly regulated. This editorial focuses on the role of nicotine,a mitogen, in the induction of signaling pathways resulting in proliferation of pancreatic tumor cells and compares these events with those in normal acinar cells isolated from the rat pancreas. The data shows striking similarities between these two cellular systems.In addition, the editorial reviews very recent literature of the contribution of MAPK signaling in cell lines associated with human diseases. A prospective cellular model of nicotine induced activation of MAPK cascade is presented.

Bone marrow-derived cultured mast cells and peritoneal mast cells as targets of a growth activity secreted by BALB/3T3 fibroblasts

International Nuclear Information System (INIS)

Jozaki, K.; Kuriu, A.; Hirota, S.; Onoue, H.; Ebi, Y.; Adachi, S.; Ma, J.Y.; Tarui, S.; Kitamura, Y.

1991-01-01

When fibroblast cell lines were cultured in contact with bone marrow-derived cultured mast cells (CMC), both NIH/3T3 and BALB/3T3 cell lines supported the proliferation of CMC. In contrast, when contact between fibroblasts and CMC was prohibited by Biopore membranes or soft agar, only BALB/3T3 fibroblasts supported CMC proliferation, suggesting that BALB/3T3 but not NIH/3T3 cells secreted a significant amount of a mast cell growth activity. Moreover, the BALB/3T3-derived growth activity induced the incorporation of [3H]thymidine by CMC and the clonal growth of peritoneal mast cells in methylcellulose. The mast cell growth activity appeared to be different from interleukin 3 (IL-3) and interleukin 4 (IL-4), because mRNAs for these interleukins were not detectable in BALB/3T3 fibroblasts. Although mast cells are genetically deficient in tissues of W/Wv mice, CMC did develop when bone marrow cells of W/Wv mice were cultured with pokeweed mitogen-stimulated spleen cell-conditioned medium. Because BALB/3T3 fibroblast-conditioned medium (BALB-FCM) did not induce the incorporation of [3H]thymidine by W/Wv CMC, the growth activity in BALB-FCM appeared to be a ligand for the receptor encoded by the W (c-kit) locus. Because CMC and peritoneal mast cells are obtained as homogeneous suspensions rather easily, these cells may be potentially useful as targets for the fibroblast-derived mast cell growth activity

Cancer Cell-derived Exosomes Induce Mitogen-activated Protein Kinase-dependent Monocyte Survival by Transport of Functional Receptor Tyrosine Kinases.

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Song, Xiao; Ding, Yanping; Liu, Gang; Yang, Xiao; Zhao, Ruifang; Zhang, Yinlong; Zhao, Xiao; Anderson, Gregory J; Nie, Guangjun

2016-04-15

Tumor-associated macrophages (TAM) play pivotal roles in cancer initiation and progression. Monocytes, the precursors of TAMs, normally undergo spontaneous apoptosis within 2 days, but can subsist in the inflammatory tumor microenvironment for continuous survival and generation of sufficient TAMs. The mechanisms underlying tumor-driving monocyte survival remain obscure. Here we report that cancer cell-derived exosomes were crucial mediators for monocyte survival in the inflammatory niche. Analysis of the survival-promoting molecules in monocytes revealed that cancer cell-derived exosomes activated Ras and extracellular signal-regulated kinases in the mitogen-activated protein kinase (MAPK) pathway, resulting in the prevention of caspase cleavage. Phosphorylated receptor tyrosine kinases (RTKs), such as phosphorylated epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER-2), were abundantly expressed in cancer cell-derived exosomes. Knock-out of EGFR or/and HER-2, or alternatively, inhibitors against their phosphorylation significantly disturbed the exosome-mediated activation of the MAPK pathway, inhibition of caspase cleavage, and increase in survival rate in monocytes. Moreover, the deprived survival-stimulating activity of exosomes due to null expression of EGFR and HER-2 could be restored by activation of another RTK, insulin receptor. Overall, our study uncovered a mechanism of tumor-associated monocyte survival and demonstrated that cancer cell-derived exosomes can stimulate the MAPK pathway in monocytes through transport of functional RTKs, leading to inactivation of apoptosis-related caspases. This work provides insights into the long sought question on monocyte survival prior to formation of plentiful TAMs in the tumor microenvironment. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Comparative Molecular Dynamics Simulations of Mitogen-Activated Protein Kinase-Activated Protein Kinase 5

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Inger Lindin

2014-03-01

Full Text Available The mitogen-activated protein kinase-activated protein kinase MK5 is a substrate of the mitogen-activated protein kinases p38, ERK3 and ERK4. Cell culture and animal studies have demonstrated that MK5 is involved in tumour suppression and promotion, embryogenesis, anxiety, cell motility and cell cycle regulation. In the present study, homology models of MK5 were used for molecular dynamics (MD simulations of: (1 MK5 alone; (2 MK5 in complex with an inhibitor; and (3 MK5 in complex with the interaction partner p38α. The calculations showed that the inhibitor occupied the active site and disrupted the intramolecular network of amino acids. However, intramolecular interactions consistent with an inactive protein kinase fold were not formed. MD with p38α showed that not only the p38 docking region, but also amino acids in the activation segment, αH helix, P-loop, regulatory phosphorylation region and the C-terminal of MK5 may be involved in forming a very stable MK5-p38α complex, and that p38α binding decreases the residual fluctuation of the MK5 model. Electrostatic Potential Surface (EPS calculations of MK5 and p38α showed that electrostatic interactions are important for recognition and binding.

ASH1L Suppresses Matrix Metalloproteinase through Mitogen-activated Protein Kinase Signaling Pathway in Pulpitis.

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Bei, Yin; Tianqian, Hui; Fanyuan, Yu; Haiyun, Luo; Xueyang, Liao; Jing, Yang; Chenglin, Wang; Ling, Ye

2017-02-01

Pulpitis is an inflammation of dental pulp produced by a response to external stimuli. The response entails substantial cellular and molecular activities. Both genetic and epigenetic regulators contribute to the occurrence of pulpitis. However, the epigenetic mechanisms are still poorly understood. In this research, we studied the role of the absent, small, or homeotic-like (ASH1L) gene in the process of pulpitis. Human dental pulp cells (HDPCs) were stimulated with proinflammatory cytokine tumor necrosis factor alpha (TNF-α). Gene expression profiling was performed to assess the occurrence of epigenetic regulators. Pulp tissue from rat experimental pulpitis was subjected to immunofluorescence to detect the occurrence of ASH1L and trimethylation of lysine 4 histone 3 (H3K4me3). The presence of ASH1L in HDPCs that had been generated by TNF-α stimulation was analyzed by Western blot procedures and cellular immunofluorescence. Once detected, ASH1L was silenced through the use of specific small interfering RNA. The effects of ASH1L on the occurrence and operation of matrix metalloproteinases (MMPs) were then tested by analysis of quantitative polymerase chain reactions, Western blotting, and zymography. Chromatin immunoprecipitation was performed to detect whether ASH1L and H3K4me3 were present in the promoter regions of MMPs. We then used Western blot procedures to examine the nuclear factor kappa B and the mitogen-activated protein kinase (MAPK) responses to the silencing of ASH1L. We also examined the specific pathway involved in ASH1L regulation of the MMPs. After stimulating HDPCs with TNF-α, ASH1L emerged as 1 of the most strongly induced epigenetic mediators. We found that TNF-α treatment induced the expression of ASH1L through the nuclear factor kappa B and MAPK signal pathways. ASH1L was found in both the nucleus and the cytoplasm. TNF-α treatment was particularly active in inducing the accumulation of ASH1L in cellular cytoplasm. As is also consistent

In vitro, inhibition of mitogen-activated protein kinase pathways protects against bupivacaine- and ropivacaine-induced neurotoxicity

NARCIS (Netherlands)

Lirk, Philipp; Haller, Ingrid; Colvin, Hans Peter; Lang, Leopold; Tomaselli, Bettina; Klimaschewski, Lars; Gerner, Peter

2008-01-01

Animal models show us that specific activation of the p38 mitogen-activated protein kinase (MAPK) may be a pivotal step in lidocaine neurotoxicity, but this has not been investigated in the case of two very widely used local anesthetics, bupivacaine and ropivacaine. We investigated the hypotheses

The N-terminal of a heparin-binding sperm membrane mitogen possess lectin-like sequence

International Nuclear Information System (INIS)

Mor, Visesato; Chatterjee, Tapati

2007-01-01

Glycosaminoglycans like heparin and heparin sulfate in follicular fluid induce changes in the intracellular environment during the spermatozoal functional maturation. We previously reported the isolation, purification and partial characterization of a heparin binding sperm membrane protein (HBSM). In the present study, the amino acids analysis provided evidence of a single sequence, which suggest the homogeneity of the purified HBSM. Fourteen amino acids- 1 A D T I V A V E L D T Y P N 14 -correspond to the amino terminal sequence of Concanavalin A (Con A) and contain 45.2% carbohydrate by weight. HBSM possess mitogenic property on lymphocytes with comparable magnitude to the well-known mitogen; Con A, inducing 83% radiolabel thymidine incorporation in growing lymphocytes. Unlike Con A, there was no agglutination of cell by HBSM upto 5 ng/ml concentration. Interestingly, we found that heparin and chondroitin sulfate-conjugated HBSM inhibit the proliferative activity. Similar effect was also found with an in-house isolate sulfated glycans; G-I (28% sulfate). In contrast, there was no inhibition by the desulfated form; G-ID. Altogether, our data suggest that the mechanism of cell proliferative pathway may be different for HBSM and Con A

Stimulation of JNK Phosphorylation by the PTTH in Prothoracic Glands of the Silkworm, Bombyx mori

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Shi-Hong Gu

2018-02-01

Full Text Available In this study, phosphorylation of c-Jun N-terminal kinase (JNK by the prothoracicotropic hormone (PTTH was investigated in prothoracic glands (PGs of the silkworm, Bombyx mori. Results showed that JNK phosphorylation was stimulated by the PTTH in time- and dose-dependent manners. In vitro activation of JNK phosphorylation in PGs by the PTTH was also confirmed in an in vivo experiment, in which a PTTH injection greatly increased JNK phosphorylation in PGs of day-6 last instar larvae. JNK phosphorylation caused by PTTH stimulation was greatly inhibited by U73122, a potent and specific inhibitor of phospholipase C (PLC and an increase in JNK phosphorylation was also detected when PGs were treated with agents (either A23187 or thapsigargin that directly elevated the intracellular Ca2+ concentration, thereby indicating involvement of PLC and Ca2+. Pretreatment with an inhibitor (U0126 of mitogen-activated protein kinase (MAPK/extracellular signal-regulated kinase (ERK kinase (MEK and an inhibitor (LY294002 of phosphoinositide 3-kinase (PI3K failed to significantly inhibit PTTH-stimulated JNK phosphorylation, indicating that ERK and PI3K were not related to JNK. We further investigated the effect of modulation of the redox state on JNK phosphorylation. In the presence of either an antioxidant (N-acetylcysteine, NAC or diphenylene iodonium (DPI, PTTH-stimulated JNK phosphorylation was blocked. The JNK kinase inhibitor, SP600125, markedly inhibited PTTH-stimulated JNK phosphorylation and ecdysteroid synthesis. The kinase assay of JNK in PGs confirmed its stimulation by PTTH and inhibition by SP600125. Moreover, PTTH treatment did not affect JNK or Jun mRNA expressions. Based on these findings, we concluded that PTTH stimulates JNK phosphorylation in Ca2+- and PLC-dependent manners and that the redox-regulated JNK signaling pathway is involved in PTTH-stimulated ecdysteroid synthesis in B. mori PGs.

Harmonic Analyzing of the Double PWM Converter in DFIG Based on Mathematical Model

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Jing Liu

2017-12-01

Full Text Available Harmonic pollution of double fed induction generators (DFIGs has become a vital concern for its undesirable effects on power quality issues of wind generation systems and grid-connected system, and the double pulse width modulation (PWMconverter is one of the main harmonic sources in DFIGs. Thus the harmonic analysis of the converter in DFIGs is a necessary step to evaluate their harmonic pollution of DFIGs. This paper proposes a detailed harmonic modeling method to discuss the main harmonic components in a converter. In general the harmonic modeling could be divided into the low-order harmonic part (up to 30th order and the high-order harmonic part (greater than order 30 parts in general. The low-order harmonics are produced by the circuit topology and control algorithm, and the harmonic component will be different if the control strategy changes. The high-order harmonics are produced by the modulation of the switching function to the dc variable. In this paper, the low-order harmonic modeling is established according to the directions of power flow under the vector control (VC, and the high-order harmonic modeling is established by the switching function of space vector PWM and dc currents. Meanwhile, the simulations of harmonic a components in a converter are accomplished in a real time digital simulation system. The results indicate that the proposed modeling could effectively show the harmonics distribution of the converter in DFIGs.

Purification and characterization of a mucin specific mycelial lectin from Aspergillus gorakhpurensis: application for mitogenic and antimicrobial activity.

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Ram Sarup Singh

Full Text Available Lectins are carbohydrate binding proteins or glycoproteins that bind reversibly to specific carbohydrates present on the apposing cells, which are responsible for their ability to agglutinate red blood cells, lymphocytes, fibroblasts, etc. Interest in lectins has been intensified due to their carbohydrate specificity as they can be valuable reagents for the investigation of cell surface sugars, purification and characterization of glycoproteins. The present study reports the purification, characterization and evaluation of mitogenic and antimicrobial potential of a mycelial lectin from Aspergillus gorakhpurensis.Affinity chromatography on mucin-sepharose column was carried out for purification of Aspergillus gorakhpurensis lectin. The lectin was characterized for physico-chemical parameters. Mitogenic potential of the lectin was evaluated against splenocytes of Swiss albino mice by MTT assay. Antimicrobial activity of the purified lectin has also been evaluated by disc diffusion assay.Single-step affinity purification resulted in 18.6-fold purification of the mycelial lectin. The molecular mass of the lectin was found to be 70 kDa and it was composed of two subunits of 34.8 kDa as determined by gel filtration chromatography, SDS-PAGE and MALDI-TOF analysis. pH optima of the lectin was found to be 6.5-9.5, while optimum temperature for lectin activity was 20-30 °C. Lectin was stable within a pH range of 7.0-10.5 and showed fair thermostability. EDTA did not affect lectin activity whereas it was found susceptible to the denaturants tested. MTT assay revealed strong mitogenic potential of A. gorakhpurensis lectin at a concentration upto 150 µg/mL. Antimicrobial activity assay showed its potent antibacterial activity against Bacillus cereus, Staphylococcous aureus and Escherichia coli and marginal antifungal activity against Saccharomyces cerevisiae.This is the first report on the mitogenic and antimicrobial potential of Aspergillus gorakhpurensis

Purification and characterization of a mucin specific mycelial lectin from Aspergillus gorakhpurensis: application for mitogenic and antimicrobial activity.

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Singh, Ram Sarup; Kaur, Hemant Preet; Singh, Jatinder

2014-01-01

Lectins are carbohydrate binding proteins or glycoproteins that bind reversibly to specific carbohydrates present on the apposing cells, which are responsible for their ability to agglutinate red blood cells, lymphocytes, fibroblasts, etc. Interest in lectins has been intensified due to their carbohydrate specificity as they can be valuable reagents for the investigation of cell surface sugars, purification and characterization of glycoproteins. The present study reports the purification, characterization and evaluation of mitogenic and antimicrobial potential of a mycelial lectin from Aspergillus gorakhpurensis. Affinity chromatography on mucin-sepharose column was carried out for purification of Aspergillus gorakhpurensis lectin. The lectin was characterized for physico-chemical parameters. Mitogenic potential of the lectin was evaluated against splenocytes of Swiss albino mice by MTT assay. Antimicrobial activity of the purified lectin has also been evaluated by disc diffusion assay. Single-step affinity purification resulted in 18.6-fold purification of the mycelial lectin. The molecular mass of the lectin was found to be 70 kDa and it was composed of two subunits of 34.8 kDa as determined by gel filtration chromatography, SDS-PAGE and MALDI-TOF analysis. pH optima of the lectin was found to be 6.5-9.5, while optimum temperature for lectin activity was 20-30 °C. Lectin was stable within a pH range of 7.0-10.5 and showed fair thermostability. EDTA did not affect lectin activity whereas it was found susceptible to the denaturants tested. MTT assay revealed strong mitogenic potential of A. gorakhpurensis lectin at a concentration upto 150 µg/mL. Antimicrobial activity assay showed its potent antibacterial activity against Bacillus cereus, Staphylococcous aureus and Escherichia coli and marginal antifungal activity against Saccharomyces cerevisiae. This is the first report on the mitogenic and antimicrobial potential of Aspergillus gorakhpurensis lectin. The

Macrophage colony-stimulating factor, CSF-1, and its proto-oncogene-encoded receptor

International Nuclear Information System (INIS)

Sherr, C.J.; Rettenmier, C.W.; Roussel, M.F.

1988-01-01

The macrophage colony-stimulating factor, CSF-1, or M-CSF, is one of a family of hematopoietic growth factors that stimulates the proliferation of monocytes, macrophages, and their committed bone marrow progenitors. Unlike pluripotent hemopoietins such as granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-3 (IL-3 or multi-CSF), which affect the growth of myeloid cells of several different hematopoietic lineages, CSF-1 acts only on cells of the mononuclear phagocyte series to stimulate their growth and enhance their survival. Retroviral transduction of the feline c-fms gene in the Susan McDonough and Hardy Zuckerman-5 (HZ-5) strains of feline sarcoma virus (FeSV) led to genetic alterations that endowed the recombined viral oncogene (v-fms) with the ability to transform cells in culture morphologically and to induce firbrosarcomas and hematopoietic neoplasms in susceptible animals. The v-fms oncogene product differs from the normal CSF-1 receptor in certain of its cardinal biochemical properties, most notably in exhibiting constitutively high basal levels of tyrosine kinase activity in the absence of its ligand. Comparative studies of the c-fms and v-fms genes coupled with analyses of engineered mutants and receptor chimeras have begun to pinpoint pertinent genetic alterations in the normal receptor gene that unmask its latent oncogenic potential. In addition, the availability of biologically active c-fms, v-fms, and CSF-1 cDNAs has allowed these genes to be mobilized and expressed in naive cells, thereby facilitating assays for receptor coupling with downstream components of the mitogenic pathway in diverse cell types

Naturally induced secretions of the potato cyst nematode co-stimulate the proliferation of both tobacco leaf protoplasts and human peripheral blood mononuclear cells.

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Goverse, A; Rouppe van der Voort, J; Roppe van der Voort, C; Kavelaars, A; Smant, G; Schots, A; Bakker, J; Helder, J

1999-10-01

Naturally induced secretions from infective juveniles of the potato cyst nematode Globodera rostochiensis co-stimulate the proliferation of tobacco leaf protoplasts in the presence of the synthetic phytohormones alpha-naphthaleneacetic acid (NAA) and 6-benzylaminopurine (BAP). With the use of a protoplast-based bioassay, a low-molecular-weight peptide(s) (cyst nematode secretions also co-stimulated mitogenesis in human peripheral blood mononuclear cells (PBMC). The stimulation of plant cells isolated from nontarget tissue--these nematodes normally invade the roots of potato plants--suggests the activation of a general signal transduction mechanism(s) by an oligopeptide(s) secreted by the nematode. Whether a similar oligopeptide-induced mechanism underlies human PBMC activation remains to be investigated. Reactivation of the cell cycle is a crucial event in feeding cell formation by cyst nematodes. The secretion of a mitogenic low-molecular-weight peptide(s) by infective juveniles of the potato cyst nematode could contribute to the redifferentiation of plant cells into such a feeding cell.

PDGF stimulation of Mueller cell proliferation: Contributions of c-JNK and the PI3K/Akt pathway

International Nuclear Information System (INIS)

Moon, Sang Woong; Chung, Eun Jee; Jung, Sun-Ah; Lee, Joon H.

2009-01-01

Platelet-derived growth factor (PDGF) has a critical role in proliferative vitreoretinopathy (PVR) as a chemoattractant and mitogen for retinal pigment epithelial cells and retinal glial cells. Here, we investigated the potential effects of PDGF on the proliferation of Mueller cells and the intracellular signaling pathway mediating these changes. PDGF induced Mueller cell proliferation and increased phosphorylation of the PDGF receptor (PDGFR), as shown by an MTT assay and immunoprecipitation analyses. Both effects were blocked by JNJ, a PDGFR-selective tyrosine kinase inhibitor. PDGF also stimulated phosphorylation of c-JNK and Akt. PDGF-induced Mueller cell proliferation was significantly reduced by pre-treatment with SP600125 and LY294002, inhibitors of c-JNK and Akt phosphorylation, respectively. Our findings collectively indicate that PDGF-stimulated Mueller cell proliferation occurs via activation of the c-JNK and PI3K/Akt signaling pathways. These data provide useful information in establishing the role of Mueller cells in the development of proliferative vitreoretinopathy.

Development of Digital Hysteresis Current Control with PLL Loop Gain Compensation Strategy for PWM Inverters with Constant Switching Frequency

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N. Belhaouchet

2008-03-01

Full Text Available Hysteresis current control is one of the simplest techniques used to control the magnitude and phase angle of motor current for motor drives systems. However, this technique presents several disadvantages such as operation at variable switching frequency which can reveal problems of filtering, interference between the phases in the case of the three-phase systems with insulated neutral connection or delta connection, and irregularity of the modulation pulses which especially causes an acoustic noise on the level of the machine for the high power drive. In this paper, a new technique is proposed for a variable-hysteresis-band controller based on dead beat control applied to three phase voltage source PWM inverters feeding AC motors. Its main aim is firstly ensure a constant switching frequency and secondly the synchronization of modulation pulses using the phase-locked-loop with loop gain compensation in order to ensure a better stability. The behavior of the proposed technique is verified by simulation.

Stimulation with Concanavalin-A Induces IL-17 Production by Canine Peripheral T Cells

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Michelle G. Ritt

2015-04-01

Full Text Available The characteristics of canine IL-17-producing cells are incompletely understood. Expression of mRNA encoding orthologs of IL-17 and the IL-17 receptor has been documented in tissues from dogs with arthritis, inflammatory bowel disease, and lymphoma; however, no associations have been found between IL-17 gene expression and disease phenotype in these conditions. Robust assessment of the role of IL-17-producing cells in dogs will require measuring the frequency of these cells in health and disease in balance with other lymphocyte subsets. The aim of this study was to confirm that the T-cell IL-17 response in dogs is evolutionarily conserved. Canine peripheral blood mononuclear cells were stimulated with Concanavalin A with or without polarizing cytokines. We used a canine specific IL-17 ELISA and flow cytometry to identify IL-17-producing T cells. Accumulation of intracellular IL-17 was observed in stimulated CD4 and CD8 T cells. The addition of pro-inflammatory cytokines appeared to enhance polarization of canine CD4 T cells to the Th17 phenotype. Conversely, the addition of IL-2 in the presence of TGF-β resulted in expansion of Treg cells. We conclude that canine IL-17-producing cells behave similarly to those from humans and mice when stimulated with mitogens and polarized with pro-inflammatory or immune regulatory cytokines.

In vitro cell-mediated immunity studies of plutonium-exposed beagle dogs

International Nuclear Information System (INIS)

Morris, J.E.; Graham, T.; Park, J.F.

1980-01-01

Mitogen-induced activation was measured in spleen and mesenteric lymph node cell preparations from dogs exposed to a single inhalation exposure of plutonium oxide ( 238 Pu or 239 Pu). Reduced stimulation indices of splenic lymphocytes from exposed animals suggest that a reduction in lymphocyte function has occurred in this tissue. No apparent reduction in mitogen stimulation indices was observed in mesenteric lymph node cultures

Glioma-secreted soluble factors stimulate microglial activation: The role of interleukin-1β and tumor necrosis factor-α.

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Hwang, Ji-Sun; Jung, Eun-Hye; Kwon, Mi-Youn; Han, Inn-Oc

2016-09-15

We aimed to elucidate the effect of soluble factors secreted by glioma on microglial activation. Conditioned medium (CM) from glioma cells, CRT-MG and C6, significantly induced nitric oxide (NO) production and stimulated the mRNA expression of inducible NO synthase (iNOS), interleukin (IL)-1beta, IL-6, tumor necrosis factor-alpha (TNF-α) and cyclooxygenase 2 (COX-2) in BV2 cells. Glioma CM stimulated p38 mitogen-activated protein kinase (MAPK) phosphorylation, and a p38 MAPK inhibitor, SB203580, suppressed CM-induced NO production in BV2 cells. In addition, CM stimulated nuclear factor-kappaB (NF-κB) DNA binding and transcriptional activity, which was repressed by SB203580. Gliomas displayed higher mRNA expression and release of TNF-α and IL-1β than primary astrocyte cells. Neutralization of TNF-α and IL-1β in C6-CM using a neutralizing antibody inhibited NO/iNOS expression in BV-2 cells. These results indicate potential contribution of diffusible tumor-derived factors to regulate microglial activation and subsequent tumor microenvironment. Copyright © 2016. Published by Elsevier B.V.

Effect of /sup 32/P treatment for polycythaemia vera on blood lymphocyte subpopulations and their functions

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Petrini, B.; Wasserman, J.; Stedingk, L.V.; Blomgren, H.; Svedmyr, E.; Schnell, P.O.

1987-01-01

The influence of /sup 32/P treatment on the blood lymphocyte population was examined in 16 patiens with polycythaemia vera who had not previously been treated with cytotoxic drugs or irradiation. Before treatment the lymphocyte counts were within the normal range but the expression of certain membrane structures, as detected by monoclonal antibodies directed against total T cells (CD 3 and 5), helper/inducer (CD 4) and suppressor/cytotoxic T cells (CD 8), were slightly reduced. In addition, mitogenic responses of the lymphocytes to PHA and PWM-induced Ig secretion were severely impaired. Following a single oral dose of /sup 32/P (150-305 MBq), which was shown to normalize the production of erythrocytes and/or platelets, the blood lymphocyte counts were reduced by approximately 40% 12 wk after treatment. Subset analysis showed that the proportion of B cells, as identified by monoclonal antibodies (CD 20), was reduced to the highest relative extent. On the other hand, lymphocytes expressing the above T cell markers were somewhat increased. /sup 32/P treatment sharply increased PHA reactivity but it further reduced PWM-induced Ig secretion. The latter observation was in line with the finding that serum concentrations of Ig were reduced following treatment.

Procalcitonin NH2-terminal cleavage peptide has no mitogenic effect on normal human osteoblast-like cells

International Nuclear Information System (INIS)

Hassager, C.; Bonde, S.K.; Anderson, M.A.; Rink, H.; Spelsberg, T.C.; Riggs, B.L.

1991-01-01

The NH2-terminal cleavage peptide of procalcitonin (N-proCT) recently was reported to be a bone cell mitogen. The authors have investigated the effect of N-proCT on the proliferation of normal human cells that have the phenotype of mature osteoblasts (hOB cells). N-proCT treatment for 24, 48, or 96 h in concentrations from 1 nM to 1 microM did not significantly increase [3H]thymidine uptake (means ranged from -19% to 38% of control, no significant differences) in hOB cells (6-10 cell strains per experiment) plated at four different densities. However, the hOB cells responded significantly to treatment with transforming growth factor β (3 ng/ml), bovine insulin (300 micrograms/ml), or 30% fetal calf serum, which were included in all experiments as positive controls. The [3H]thymidine uptake data were confirmed in a direct cell count experiment tested at 96 h. Thus they data do not support the hypothesis that N-proCT is a potent mitogen for normal human osteoblasts

Mitogen response of B cells, but not T cells, is impaired in adult vitamin A-deficient rats

NARCIS (Netherlands)

van Bennekum, A. M.; Wong Yen Kong, L. R.; Gijbels, M. J.; Tielen, F. J.; Roholl, P. J.; Brouwer, A.; Hendriks, H. F.

1991-01-01

The effect of vitamin A deficiency on the mitogen response of splenic B and T lymphocytes was determined in adult vitamin A-deficient rats. Female weanling Brown Norway/Billingham-Rijswijk (BN/BiRij) and Sprague-Dawley rats were fed a semipurified, essentially vitamin A-free diet, which resulted in

Proliferation-stimulating effect of colony stimulating factor 2 on porcine trophectoderm cells is mediated by activation of phosphatidylinositol 3-kinase and extracellular signal-regulated kinase 1/2 mitogen-activated protein kinase.

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Wooyoung Jeong

Full Text Available Colony-stimulating factor 2 (CSF2, also known as granulocyte macrophage colony-stimulating factor, facilitates mammalian embryonic development and implantation. However, biological functions and regulatory mechanisms of action of porcine endometrial CSF2 in peri-implantation events have not been elucidated. The aim of present study was to determine changes in cellular activities induced by CSFs and to access CSF2-induced intracellular signaling in porcine primary trophectoderm (pTr cells. Differences in expression of CSF2 mRNA in endometrium from cyclic and pregnant gilts were evaluated. Endometrial CSF2 mRNA expression increases during the peri-implantation period, Days 10 to 14 of pregnancy, as compared to the estrous cycle. pTr cells obtained in Day 12 of pregnancy were cultured in the presence or absence of CSF2 (20 ng/ml and LY294002 (20 µM, U0126 (20 µM, rapamycin (20 nM, and SB203580 (20 µM. CSF2 in pTr cell culture medium at 20 ng/ml significantly induced phosphorylation of AKT1, ERK1/2, MTOR, p70RSK and RPS6 protein, but not STAT3 protein. Also, the PI3K specific inhibitor (LY294002 abolished CSF2-induced increases in p-ERK1/2 and p-MTOR proteins, as well as CSF2-induced phosphorylation of AKT1. Changes in proliferation and migration of pTr cells in response to CSF2 were examined in dose- and time-response experiments. CSF2 significantly stimulated pTr cell proliferation and, U0126, rapamycin and LY294002 blocked this CSF2-induced proliferation of pTr cells. Collectively, during the peri-implantation phase of pregnancy in pigs, endometrial CSF2 stimulates proliferation of trophectoderm cells by activation of the PI3K-and ERK1/2 MAPK-dependent MTOR signal transduction cascades.

Short communication: Camel milk ameliorates inflammatory responses and oxidative stress and downregulates mitogen-activated protein kinase signaling pathways in lipopolysaccharide-induced acute respiratory distress syndrome in rats.

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Zhu, Wei-Wei; Kong, Gui-Qing; Ma, Ming-Ming; Li, Yan; Huang, Xiao; Wang, Li-Peng; Peng, Zhen-Yi; Zhang, Xiao-Hua; Liu, Xiang-Yong; Wang, Xiao-Zhi

2016-01-01

Acute respiratory distress syndrome (ARDS) is a complex syndrome disorder with high mortality rate. Camel milk (CM) contains antiinflammatory and antioxidant properties and protects against numerous diseases. This study aimed to demonstrate the function of CM in lipopolysaccharide (LPS)-induced ARDS in rats. Camel milk reduced the lung wet:dry weight ratio and significantly reduced LPS-induced increases in neutrophil infiltration, interstitial and intra-alveolar edema, thickness of the alveolar wall, and lung injury scores of lung tissues. It also had antiinflammatory and antioxidant effects on LPS-induced ARDS. After LPS stimulation, the levels of proinflammatory cytokines (tumor necrosis factor-α, IL-10, and IL-1β) in serum and oxidative stress markers (malondialdehyde, myeloperoxidase, and total antioxidant capacity) in lung tissue were notably attenuated by CM. Camel milk also downregulated mitogen-activated protein kinase signaling pathways. Given these results, CM is a potential complementary food for ARDS treatment. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Inverter Output Filter Effect on PWM Motor Drives of a Flywheel Energy Storage System

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Santiago, Walter

2004-01-01

NASA Glenn Research Center (GRC) has been involved in the research and development of high speed flywheel systems for small satellite energy storage and attitude control applications. One research and development area has been the minimization of the switching noise produced by the pulsed width modulated (PWM) inverter that drives the flywheel permanent magnet motor/generator (PM M/G). This noise can interfere with the flywheel M/G hardware and the system avionics hampering the full speed performance of the flywheel system. One way to attenuate the inverter switching noise is by placing an AC filter at the three phase output terminals of the inverter with the filter neutral point connected to the DC link (DC bus) midpoint capacitors. The main benefit of using an AC filter in this fashion is the significant reduction of the inverter s high dv/dt switching and its harmonics components. Additionally, common mode (CM) and differential mode (DM) voltages caused by the inverter s high dv/dt switching are also reduced. Several topologies of AC filters have been implemented and compared. One AC filter topology consists of a two-stage R-L-C low pass filter. The other topology consists of the same two-stage R-L-C low pass filter with a series connected trap filter (an inductor and capacitor connected in parallel). This paper presents the analysis, design and experimental results of these AC filter topologies and the comparison between the no filter case and conventional AC filter.

Pre-ERCP infusion of semapimod, a mitogen-activated protein kinases inhibitor, lowers post-ERCP hyperamylasemia but not pancreatitis incidence

NARCIS (Netherlands)

van Westerloo, David J.; Rauws, Erik A.; Hommes, Daan; de Vos, Alex F.; van der Poll, Tom; Powers, Barbara L.; Fockens, Paul; Dijkgraaf, Marcel G. W.; Bruno, Marco J.

2008-01-01

BACKGROUND: Acute pancreatitis and hyperamylasemia are frequent complications of an ERCP. Semapimod is a synthetic guanylhydrazone that inhibits the mitogen-activated protein kinase (MAPK) pathway, macrophage activation, and the production of several inflammatory cytokines. OBJECTIVE: This study

Subcellular distribution and chemical forms of cadmium in Phytolacca americana L

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Fu Xiaoping; Dou Changming [Ministry of Agriculture Key Laboratory of Non-point Source Pollution Control, Institute of Environmental Science and Technology, Zhejiang University, Hangzhou 310029 (China); Chen Yingxu, E-mail: yingxu_chen@hotmail.com [Ministry of Agriculture Key Laboratory of Non-point Source Pollution Control, Institute of Environmental Science and Technology, Zhejiang University, Hangzhou 310029 (China); Chen Xincai; Shi Jiyan; Yu Mingge; Xu Jie [Ministry of Agriculture Key Laboratory of Non-point Source Pollution Control, Institute of Environmental Science and Technology, Zhejiang University, Hangzhou 310029 (China)

2011-02-15

Phytolacca americana L. (pokeweed) is a promising species for Cd phytoextraction with large biomass and fast growth rate. To further understand the mechanisms involved in Cd tolerance and detoxification, the present study investigated subcellular distribution and chemical forms of Cd in pokeweed. Subcellular fractionation of Cd-containing tissues indicated that both in root and leaves, the majority of the element was located in soluble fraction and cell walls. Meanwhile, Cd taken up by pokeweed existed in different chemical forms. Results showed that the greatest amount of Cd was found in the extraction of 80% ethanol in roots, followed by 1 M NaCl, d-H{sub 2}O and 2% HAc, while in leaves and stems, most of the Cd was extracted by 1 M NaCl, and the subdominant amount of Cd was extracted by 80% ethanol. It could be suggested that Cd compartmentation with organo-ligands in vacuole or integrated with pectates and proteins in cell wall might be responsible for the adaptation of pokeweed to Cd stress.

Aqueous fraction from Cuscuta japonica seed suppresses melanin synthesis through inhibition of the p38 mitogen-activated protein kinase signaling pathway in B16F10 cells.

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Jang, Ji Yeon; Kim, Ha Neui; Kim, Yu Ri; Choi, Yung Hyun; Kim, Byung Woo; Shin, Hwa Kyoung; Choi, Byung Tae

2012-05-07

Semen cuscutae has been used traditionally to treat pimples and alleviate freckles and melasma in Korea. The present study aimed to investigate the inhibitory effect of Cuscuta japonica Choisy seeds on alpha-melanocyte-stimulating hormone (α-MSH)-induced melanogenesis. The aqueous fraction from Semen cuscutae (AFSC) was used to determine anti-melanogenic effects by examination of cellular melanin contents, tyrosinase activity assay, cAMP assay and Western blot analysis for melanin synthesis-related signaling proteins in B16F10 mouse melanoma cells. AFSC markedly inhibited α-MSH-induced melanin synthesis and tyrosinase activity, and also decreased α-MSH-induced expression of microphthalmia-associated transcription factor (MITF) and tyrosinase-related proteins (TRPs). Moreover, AFSC significantly decreased the level of phosphorylated p38 mitogen-activated protein kinase (MAPK) signaling through the down-regulation of α-MSH-induced cAMP. Furthermore, we confirmed that the specific inhibitor of p38 MAPK (SB203580)-mediated suppressed melanin synthesis and tyrosinase activity was further attenuated by AFSC. AFSC also further decreased SB203580-mediated suppression of MITF and TRP expression. These results indicate that AFSC inhibits p38 MAPK phosphorylation with suppressed cAMP levels and subsequently down-regulate MITF and TRP expression, which results in a marked reduction of melanin synthesis and tyrosinase activity in α-MSH-stimulated B16F10 cells. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Culicoides antigen extract stimulates equine blood mononuclear (BMN) cell proliferation and the release of eosinophil adherence-inducing factor(s).

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Mckelvie, J; Foster, A P; Hamblin, A S; Cunningham, F M

2001-04-01

Intradermal injection of a Culicoides antigen extract (CAgX) induces T lymphocyte and eosinophil accumulation in the skin of horses with sweet itch. Blood mononuclear (BMN) cells from normal ponies proliferate when stimulated by mitogen (phytohaemagglutinin, PHA) or antigen (tetanus toxoid, TT) and, as shown here, release soluble factor(s) that induce eosinophil adherence. CAgX also caused concentration dependent proliferation of BMN cells from sweet itch and normal ponies [stimulation index: 29 (13) and 17 (7) for BMN cells from sweet itch and normal ponies, respectively during the active phase of disease; 4 microg protein ml(-1)CAgX; 168 h]. A heat labile factor(s) which caused eosinophil adherence was also released [sweet itch ponies: 6.0 (1.6) per cent adherence versus 1.3 (0.4) per cent; normal ponies: 6.6 (0.5) per cent adherence versus 0.9 (0.1) per cent for supernatants from CAgX (4 microg protein ml(-1); 48 hours) stimulated versus unstimulated BMN cells, respectively]. These results suggest that soluble proteins released from T lymphocytes could affect eosinophil function in the lesional skin of sweet itch horses. Copyright 2001 Harcourt Publishers Ltd.

Cardiac imaging in RASopathies/mitogen activated protein kinase syndromes

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Rita Gravino

2014-07-01

Full Text Available RASopathies include a spectrum of disorders due to dysregulation of RAS/mitogen activated protein kinase pathway that plays an essential role in the control of the cell cycle and differentiation. As a consequence, its dysregulation has profound developmental consequences, in particular cardiac malformations. RASopathies with cardiac features are: Noonan syndrome, multiple lentigines syndrome, cardio-faciocutaneous syndrome, Costello syndrome, neurofibromatosis- 1, Legius syndrome, neurofibromatosis- Noonan syndrome. The former syndromes are associated with a high rate of cardiac involvement (60-85% and 12 genes: PTPN11, SOS1, RAF1, KRAS, HRAS, BRAF, MEK1/MAP2K1, MEK2/MAP2K2, NRAS, SHOC2, CBL and SPRED1. Although the majority of these diseases are readily distinguishable in clinical terms, an integrated imaging study of the cardiac condition associated to RASopathies helps to better define risk assessment, surveillance, and management of these patients.

Sirtuin inhibition attenuates the production of inflammatory cytokines in lipopolysaccharide-stimulated macrophages

International Nuclear Information System (INIS)

Fernandes, Cláudia A.; Fievez, Laurence; Neyrinck, Audrey M.; Delzenne, Nathalie M.; Bureau, Fabrice; Vanbever, Rita

2012-01-01

Highlights: ► Lipopolysaccharide-stimulated macrophages were treated with cambinol and sirtinol. ► Cambinol and sirtinol decreased lipopolysaccharide-induced cytokines. ► Cambinol decreased NF-κB activity but had no impact on p38 MAPK activation. ► Sirtuins are an interesting target for the treatment of inflammatory diseases. -- Abstract: In several inflammatory conditions such as rheumatoid arthritis or sepsis, the regulatory mechanisms of inflammation are inefficient and the excessive inflammatory response leads to damage to the host. Sirtuins are class III histone deacetylases that modulate the activity of several transcription factors that are implicated in immune responses. In this study, we evaluated the impact of sirtuin inhibition on the activation of lipopolysaccharide (LPS)-stimulated J774 macrophages by assessing the production of inflammatory cytokines. The pharmacologic inhibition of sirtuins decreased the production of tumour necrosis factor-alpha (TNF-α) interleukin 6 (IL-6) and Rantes. The reduction of cytokine production was associated with decreased nuclear factor kappa B (NF-κB) activity and inhibitor kappa B alpha (IκBα) phosphorylation while no impact was observed on the phosphorylation status of p38 mitogen-activated kinase (p38 MAPK). This work shows that sirtuin pharmacologic inhibitors are a promising tool for the treatment of inflammatory conditions.

Alpha-2 adrenergic stimulation triggers Achilles tenocyte hypercellularity: Comparison between two model systems.

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Backman, L J; Andersson, G; Fong, G; Alfredson, H; Scott, A; Danielson, P

2013-12-01

The histopathology of tendons with painful tendinopathy is often tendinosis, a fibrosis-like condition of unclear pathogenesis characterized by tissue changes including hypercellularity. The primary tendon cells (tenocytes) have been shown to express adrenoreceptors (mainly alpha-2A) as well as markers of catecholamine production, particularly in tendinosis. It is known that adrenergic stimulation can induce proliferation in other cells. The present study investigated the effects of an exogenously administered alpha-2 adrenergic agonist in an established in vivo Achilles tendinosis model (rabbit) and also in an in vitro human tendon cell culture model. The catecholamine producing enzyme tyrosine hydroxylase and the alpha-2A-adrenoreceptor (α2A AR) were expressed by tenocytes, and alpha-2 adrenergic stimulation had a proliferative effect on these cells, in both models. The proliferation was inhibited by administration of an α2A AR antagonist, and the in vitro model further showed that the proliferative alpha-2A effect was mediated via a mitogenic cell signaling pathway involving phosphorylation of extracellular-signal-regulated kinases 1 and 2. The results indicate that catecholamines produced by tenocytes in tendinosis might contribute to the proliferative nature of the pathology through stimulation of the α2A AR, pointing to a novel target for future therapies. The study furthermore shows that animal models are not necessarily required for all aspects of this research. © 2013 The Authors. Scand J Med Sci Sports published by John Wiley & Sons Ltd.

Effects of ketotifen on human lymphocytes in vitro and in vivo

NARCIS (Netherlands)

Petrasch, S.; van Tits, L. J.; Motulsky, H. J.; Brodde, O. E.; Michel, M. C.

1993-01-01

The effects of the antiasthmatic drug ketotifen (CAS 34580-13-7) on human mononuclear leukocytes were studied in vitro and in vivo. In vitro ketotifen concentration-dependently inhibited mitogen-stimulated lymphocyte proliferation. High ketotifen concentrations also inhibited T-lymphocyte mitogen-

Effects of synthetic and naturally occurring flavonoids on mitogen-induced proliferation of human peripheral-blood lymphocytes

International Nuclear Information System (INIS)

Hirano, Toshihiko; Oka, Kitaro; Kawashima, Etsuko; Akiba, Mitsuo

1989-01-01

Examination was made of the effects of 17 synthetic and naturally occurring flavonoids on human lymphocyte proliferation in the presence of concanavalin A as a mitogen. Twelve of the flavonoids examined were mono-hydroxy of methoxy derivatives. The mitogen-induced response of lymphocytes was evaluated from the extent of the incorporation of [ 3 H]thymidine into cells in vitro. All the compounds showed inhibitory effects; 4.5-77.7% of [ 3 H] thymidine incorporation was blocked by an 1.0 μg/ml concentration. The viability of lymphocytes before and after treatment, as assessed by a dye exclusion test, indicated no change, and thus the flavonoids may inhibit DNA synthesis. The flavonoids possessing 5-hydroxyl, 5-methoxyl and 6-methoxyl groups, and those with cyclohexyl instead of phenyl substituent (i.e. 2-cyclohexyl-benzopyran-4-one), showed the greatest inhibition. The inhibitory effect of any one of them was less than one half that of prednisolone, but essentially the same or somewhat exceeding that of bredinine of azathioprine. It would thus appear that the well-known anti-inflammatory effects of flavonoids may possibly arise in part from the inhibition of the proliferative response of lymphocytes

AMP N1-Oxide, a Unique Compound of Royal Jelly, Induces Neurite Outgrowth from PC12 Vells via Signaling by Protein Kinase A Independent of that by Mitogen-Activated Protein Kinase

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Noriko Hattori

2010-01-01

Full Text Available Earlier we identified adenosine monophosphate (AMP N1-oxide as a unique compound of royal jelly (RJ that induces neurite outgrowth (neuritegenesis from cultured rat pheochromocytoma PC12 cells via the adenosine A2A receptor. Now, we found that AMP N1-oxide stimulated the phosphorylation of not only mitogen-activated protein kinase (MAPK but also that of cAMP/calcium-response element-binding protein (CREB in a dose-dependent manner. Inhibition of MAPK activation by a MEK inhibitor, PD98059, did not influence the AMP N1-oxide-induced neuritegenesis, whereas that of protein kinase A (PKA by a selective inhibitor, KT5720, significantly reduced neurite outgrowth. AMP N1-oxide also had the activity of suppressing the growth of PC12 cells, which correlated well with the neurite outgrowth-promoting activity. KT5720 restored the growth of AMP N1-oxide-treated PC12 cells. It is well known that nerve growth factor suppresses proliferation of PC12 cells before causing stimulation of neuronal differentiation. Thus, AMP N1-oxide elicited neuronal differentiation of PC12 cells, as evidenced by generation of neurites, and inhibited cell growth through adenosine A2A receptor-mediated PKA signaling, which may be responsible for characteristic actions of RJ.

Development of an On-Line Self-Tuning FPGA-PID-PWM Control Algorithm Design for DC-DC Buck Converter in Mobile Applications

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Ahmed Sabah Al-Araji

2017-08-01

Full Text Available This paper presents a new development of an on-line hybrid self-tuning control algorithm of the Field Programmable Gate Array - Proportional Integral Derivative - Pulse Width Modulation (FPGA-PID-PWM controller for DC-DC buck converter which is used in battery operation of mobile applications. The main goal in this work is to propose structure of the hybrid Bees-PSO tuning control algorithm which has a capability of quickly and precisely searching in the global regions in order to obtain optimal gain parameters for the proposed controller to generate the best voltage control action to achieve the desired performance of the Buck converter output. Matlab simulation results and Xilinx development tool Integrated Software Environment (ISE experimental work show the robustness and effectiveness of the proposed on-line hybrid Bees-PSO tuning control algorithm in terms of obtaining smooth and unsaturated state voltage control action and minimizing the tracking voltage error of the Buck converter output. Moreover, the fitness evaluation number is reduced.

Stimulation of neuronal neurite outgrowth using functionalized carbon nanotubes

Energy Technology Data Exchange (ETDEWEB)

Matsumoto, K; Sato, C; Shimizu, N [Graduate School of Life Sciences, Toyo University, 1-1-1 Izumino, Itakura-machi, Ora-gun, Gunma 374-0193 (Japan); Naka, Y [Bio-Nano Electronics Research Center, Toyo University, 2100 Kujirai, Kawagoe-shi, Saitama 350-8585 (Japan); Whitby, R, E-mail: shimizu@toyonet.toyo.ac.jp [School of Pharmacy and Biomolecular Sciences, University of Brighton, Cockroft Building, Lewes Road, Brighton BN2 4GJ (United Kingdom)

2010-03-19

Low concentrations (0.11-1.7 {mu}g ml{sup -1}) of functionalized carbon nanotubes (CNTs), which are multi-walled CNTs modified by amino groups, when added with nerve growth factor (NGF), promoted outgrowth of neuronal neurites in dorsal root ganglion (DRG) neurons and rat pheochromocytoma cell line PC12h cells in culture media. The quantity of active extracellular signal-regulated kinase (ERK) was higher after the addition of both 0.85 {mu}g ml{sup -1} CNTs and NGF than that with NGF alone. CNTs increased the number of cells with neurite outgrowth in DRG neurons and PC12h cells after the inhibition of the ERK signaling pathway using a mitogen-activated protein kinase (MAPK)/ERK kinase (MEK) inhibitor. Active ERK proteins were detected in MEK inhibitor-treated neurons after the addition of CNTs to the culture medium. These results demonstrate that CNTs may stimulate neurite outgrowth by activation of the ERK signaling pathway. Thus, CNTs are biocompatible and are promising candidates for biological applications and devices.

Induction of the immune response suppression in mice inoculated with Candida albicans.

Science.gov (United States)

Valdez, J C; Mesón, D E; Sirena, A; de Petrino, S F; Eugenia, M; de Jorrat, B B; de Valdex, M G

1986-03-01

There is a controversy in respect to the immunological response (humoral or cellular) concerning the defense against Candida albicans. Candidosis would induce sub-populations of suppressor cells in the host cell-immune response. This report tries to show the effect of different doses of C. albicans (alive or heat-killed) on the expression of cell-mediated and humoral immunity. The effect upon cell immunity was determined by inoculating different lots of singeneic mice, doses of varied concentration of C. albicans and checking for delayed-type hipersensitivity (D.T.H.). D.T.H. was also controlled in syngeneic normal mice which had previously been injected with inoculated mice spleen cells. Humoral immunity was assayed by measuring the induced blastogenesis by Pokeweed Mitogen on spleen mononuclear cells with different doses of C. albicans. Results obtained show that the different doses gave origin to: Suppression of humoral and cell response (10(8) alive); Suppression of only humoral response (10(6) alive); Suppression of cell response and increase of humoral response (10(9) dead); Increase of both responses (10(8) dead).

Thymus cells in myasthenia gravis selectively enhance production of anti-acetylcholine-receptor antibody by autologous blood lymphocytes

International Nuclear Information System (INIS)

Newsom-Davis, J.; Willcox, N.; Calder, L.

1981-01-01

We investigated the role of the thymus in 16 patients with myasthenia gravis without thymoma by studying the production of anti-acetylcholine-receptor antibody by thymic and blood lymphocytes cultured alone or together. In 10 responders (with the highest receptor-antibody titers in their plasma), cultured thymic cells spontaneously produced measurable receptor antibody. Receptor-antibody production by autologous blood lymphocytes was enhanced by the addition of responder's thymic cells, irradiated to abrogate antibody production and suppression (P<0.01). This enhancement was greater and more consistent than that by pokeweed mitogen; it depended on viable thymic cells, appeared to be selective for receptor antibody, and correlated with the ratio of thymic helper (OKT4-positive or OKT4+) to suppressor (OKT8+) T cells (P<0.01). These results suggest that myasthenic thymus contains cell-bound acetylcholine-receptor-like material or specific T cells (or both) that can aid receptor-antibody production. This may be relevant to the benefits of thymectomy in myasthenia and to the breakdown in self-tolerance in this and other autoimmune diseases

Thymus cells in myasthenia gravis selectively enhance production of anti-acetylcholine-receptor antibody by autologous blood lymphocytes

Energy Technology Data Exchange (ETDEWEB)

Newsom-Davis, J.; Willcox, N.; Calder, L.

1981-11-26

We investigated the role of the thymus in 16 patients with myasthenia gravis without thymoma by studying the production of anti-acetylcholine-receptor antibody by thymic and blood lymphocytes cultured alone or together. In 10 responders (with the highest receptor-antibody titers in their plasma), cultured thymic cells spontaneously produced measurable receptor antibody. Receptor-antibody production by autologous blood lymphocytes was enhanced by the addition of responder's thymic cells, irradiated to abrogate antibody production and suppression (P<0.01). This enhancement was greater and more consistent than that by pokeweed mitogen; it depended on viable thymic cells, appeared to be selective for receptor antibody, and correlated with the ratio of thymic helper (OKT4-positive or OKT4+) to suppressor (OKT8+) T cells (P<0.01). These results suggest that myasthenic thymus contains cell-bound acetylcholine-receptor-like material or specific T cells (or both) that can aid receptor-antibody production. This may be relevant to the benefits of thymectomy in myasthenia and to the breakdown in self-tolerance in this and other autoimmune diseases.

The Mitogen-Activated Protein Kinase p38 alpha Regulates Tubular Damage in Murine Anti-Glomerular Basement Membrane Nephritis

NARCIS (Netherlands)

Mueller, Ralf; Daniel, Christoph; Hugo, Christian; Amann, Kerstin; Mielenz, Dirk; Endlich, Karlhans; Braun, Tobias; van der Veen, Betty; Heeringa, Peter; Schett, Georg; Zwerina, Jochen

2013-01-01

p38 mitogen-activated protein kinase (MAPK) is thought to play a central role in acute and chronic inflammatory responses. Whether p38MAPK plays a pathogenic role in crescentic GN (GN) and which of its four isoforms is preferentially involved in kidney inflammation is not definitely known. We thus

Activated platelet-derived growth factor β receptor and Ras-mitogen-activated protein kinase pathway in natural bovine urinary bladder carcinomas.

Science.gov (United States)

Corteggio, Annunziata; Di Geronimo, Ornella; Roperto, Sante; Roperto, Franco; Borzacchiello, Giuseppe

2012-03-01

Bovine papillomavirus types 1 or 2 (BPV-1/2) are involved in the aetiopathogenesis of bovine urinary bladder cancer. BPV-1/2 E5 activates the platelet-derived growth factor β receptor (PDGFβR). The aim of this study was to analyse the Ras/mitogen-activated protein kinase (MAPK) pathway in relation to activation of PDGFβR in natural bovine urinary bladder carcinomas. Co-immunoprecipitation and Western blot analysis demonstrated that recruitment of growth factor receptor bound protein 2 (GRB-2) and Sos-1 to the activated PDGFβR was increased in carcinomas compared to normal tissues. Higher grade bovine urinary bladder carcinomas were associated with activation of Ras, but not with activation of downstream mitogen-activated protein kinase/extracellular signal-regulated kinase (Mek 1/2) or extracellular signal-regulated kinase (Erk 1/2). Copyright © 2011 Elsevier Ltd. All rights reserved.

A new type of accelerator power supply based on voltage-type space vector PWM rectification technology

International Nuclear Information System (INIS)

Wu, Fengjun; Gao, Daqing; Shi, Chunfeng; Huang, Yuzhen; Cui, Yuan; Yan, Hongbin; Zhang, Huajian; Wang, Bin; Li, Xiaohui

2016-01-01

To solve the problems such as low input power factor, a large number of AC current harmonics and instable DC bus voltage due to the diode or thyristor rectifier used in an accelerator power supply, particularly in the Heavy Ion Research Facility in Lanzhou-Cooler Storage Ring (HIRFL-CSR), we designed and built up a new type of accelerator power supply prototype base on voltage-type space vector PWM (SVPWM) rectification technology. All the control strategies are developed in TMS320C28346, which is a digital signal processor from TI. The experimental results indicate that an accelerator power supply with a SVPWM rectifier can solve the problems above well, and the output performance such as stability, tracking error and ripple current meet the requirements of the design. The achievement of prototype confirms that applying voltage-type SVPWM rectification technology in an accelerator power supply is feasible; and it provides a good reference for design and build of this new type of power supply. - Highlights: • Applying SVPWM rectification technology in an accelerator power supply improves its grid-side performance. • New Topology and its control strategies make an accelerator power supply have bidirectional power flow ability. • Hardware and software of controller provide a good reference for design of this new type of power supply.

A new type of accelerator power supply based on voltage-type space vector PWM rectification technology

Energy Technology Data Exchange (ETDEWEB)

Wu, Fengjun, E-mail: wufengjun@impcas.ac.cn [Institute of Modern Physics, CAS, Lanzhou 730000 (China); University of Chinese Academy of Sciences, Beijing 100049 (China); Gao, Daqing; Shi, Chunfeng; Huang, Yuzhen [Institute of Modern Physics, CAS, Lanzhou 730000 (China); Cui, Yuan [Institute of Modern Physics, CAS, Lanzhou 730000 (China); University of Chinese Academy of Sciences, Beijing 100049 (China); Yan, Hongbin [Institute of Modern Physics, CAS, Lanzhou 730000 (China); Zhang, Huajian [Institute of Modern Physics, CAS, Lanzhou 730000 (China); University of Chinese Academy of Sciences, Beijing 100049 (China); Wang, Bin [University of Chinese Academy of Sciences, Beijing 100049 (China); Li, Xiaohui [Institute of Modern Physics, CAS, Lanzhou 730000 (China)

2016-08-01

To solve the problems such as low input power factor, a large number of AC current harmonics and instable DC bus voltage due to the diode or thyristor rectifier used in an accelerator power supply, particularly in the Heavy Ion Research Facility in Lanzhou-Cooler Storage Ring (HIRFL-CSR), we designed and built up a new type of accelerator power supply prototype base on voltage-type space vector PWM (SVPWM) rectification technology. All the control strategies are developed in TMS320C28346, which is a digital signal processor from TI. The experimental results indicate that an accelerator power supply with a SVPWM rectifier can solve the problems above well, and the output performance such as stability, tracking error and ripple current meet the requirements of the design. The achievement of prototype confirms that applying voltage-type SVPWM rectification technology in an accelerator power supply is feasible; and it provides a good reference for design and build of this new type of power supply. - Highlights: • Applying SVPWM rectification technology in an accelerator power supply improves its grid-side performance. • New Topology and its control strategies make an accelerator power supply have bidirectional power flow ability. • Hardware and software of controller provide a good reference for design of this new type of power supply.

Heat Shock Protein 70 Negatively Regulates TGF-β-Stimulated VEGF Synthesis via p38 MAP Kinase in Osteoblasts

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Go Sakai

2017-11-01

Full Text Available Background/Aims: We previously demonstrated that transforming growth factor-β (TGF-β stimulates the synthesis of vascular endothelial growth factor (VEGF through the activation of p38 mitogen-activated protein (MAP kinase in osteoblast-like MC3T3-E1 cells. Heat shock protein70 (HSP70 is a ubiquitously expressed molecular chaperone. In the present study, we investigated the involvement of HSP70 in the TGF-β-stimulated VEGF synthesis and the underlying mechanism in these cells. Methods: Culture MC3T3-E1 cells were stimulated by TGF-β. Released VEGF was measured using an ELISA assay. VEGF mRNA level was quantified by RT-PCR. Phosphorylation of each protein kinase was analyzed by Western blotting. Results: VER-155008 and YM-08, both of HSP70 inhibitors, significantly amplified the TGF-β-stimulated VEGF release. In addition, the expression level of VEGF mRNA induced by TGF-β was enhanced by VER-155008. These inhibitors markedly strengthened the TGF-β-induced phosphorylation of p38 MAP kinase. The TGF-β-induced phosphorylation of p38 MAP kinase was amplified in HSP70-knockdown cells. SB203580, an inhibitor of p38 MAP kinase, significantly suppressed the amplification by these inhibitors of the TGF-β-induced VEGF release. Conclusion: These results strongly suggest that HSP70 acts as a negative regulator in the TGF-β-stimulated VEGF synthesis in osteoblasts, and that the inhibitory effect of HSP70 is exerted at a point upstream of p38 MAP kinase.

Extracellular polysaccharides produced by Ganoderma formosanum stimulate macrophage activation via multiple pattern-recognition receptors

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Wang Cheng-Li

2012-08-01

Full Text Available Abstract Background The fungus of Ganoderma is a traditional medicine in Asia with a variety of pharmacological functions including anti-cancer activities. We have purified an extracellular heteropolysaccharide fraction, PS-F2, from the submerged mycelia culture of G. formosanum and shown that PS-F2 exhibits immunostimulatory activities. In this study, we investigated the molecular mechanisms of immunostimulation by PS-F2. Results PS-F2-stimulated TNF-α production in macrophages was significantly reduced in the presence of blocking antibodies for Dectin-1 and complement receptor 3 (CR3, laminarin, or piceatannol (a spleen tyrosine kinase inhibitor, suggesting that PS-F2 recognition by macrophages is mediated by Dectin-1 and CR3 receptors. In addition, the stimulatory effect of PS-F2 was attenuated in the bone marrow-derived macrophages from C3H/HeJ mice which lack functional Toll-like receptor 4 (TLR4. PS-F2 stimulation triggered the phosphorylation of mitogen-activated protein kinases JNK, p38, and ERK, as well as the nuclear translocation of NF-κB, which all played essential roles in activating TNF-α expression. Conclusions Our results indicate that the extracellular polysaccharides produced by G. formosanum stimulate macrophages via the engagement of multiple pattern-recognition receptors including Dectin-1, CR3 and TLR4, resulting in the activation of Syk, JNK, p38, ERK, and NK-κB and the production of TNF-α.

Immunoglobulin production in human mixed lymphocyte cultures: implications for co-cultures of cells from patients and healthy donors

International Nuclear Information System (INIS)

Ruemke, H.C.; Terpstra, F.G.; Huis, B.; Out, T.A.; Zeijlemaker, W.P.

1982-01-01

When human peripheral blood lymphocytes (PBL) are cultured in the presence of irradiated allogeneic lymphocytes, the resulting mixed lymphocyte reaction (MLR) leads to the secretion into the supernatant of substantial amounts of IgM and IgG, derived from nonirradiated responder B lymphocytes. Our data indicate that stimulation to Ig production by responder B cells may result from different types of of interactions. First, B cells and monocytes among the irradiated stimulator cells activate T responder B cells to produce Ig; second, ''responder'' B cells activate irradiated ''stimulator'' T cells, leading to a ''helper'' signal, back to the responder B cells and leading to Ig production. The latter system is radiosensitive, because allogeneic T cells, irradiated at a dose of 4000 rad or more, failed to induce Ig production by responder B cells. In some combinations of human allogeneic lymphocytes, the co-culture of the cells leads to inhibition of Ig production, both in the presence and in the absence of PWM. Thus, co-culture of allogeneic cells may cause ''positive'' as well as ''negative'' allogeneic effects. The implications of these findings for the interpretation of co-cultures that are aimed at establishing defects in lymphocytes from patients with, for example, immunodeficiencies, who fail to produce Ig in the presence of PWM are discussed

Homeostatic 'bystander' proliferation of human peripheral blood B cells in response to polyclonal T-cell stimulation in vitro.

Science.gov (United States)

Jasiulewicz, Aleksandra; Lisowska, Katarzyna A; Pietruczuk, Krzysztof; Frąckowiak, Joanna; Fulop, Tamas; Witkowski, Jacek M

2015-11-01

The mechanisms of maintenance of adequate numbers of B lymphocytes and of protective levels of immunoglobulins in the absence of antigenic (re)stimulation remain not fully understood. Meanwhile, our results presented here show that both peripheral blood naive and memory B cells can be activated strongly and non-specifically (in a mitogen-like fashion) in 5-day in vitro cultures of anti-CD3- or concanavalin A (Con A)-stimulated peripheral blood mononuclear cells of healthy people. This polyclonal, bystander activation of the B cells includes multiple divisions of most of them (assessed here by the flow cytometric technique of dividing cell tracking) and significant antibody [immunoglobulin M (IgM) and IgG] secretion. Observed proliferation of the CD19(+) B cells depends on contact with stimulated T helper (Th) cells (via CD40-CD40L interaction) and on the response of B cells to secreted interleukins IL-5, IL-10 and IL-4, and is correlated with the levels of these Th-derived molecules, while it does not involve the ligation of the BCR/CD19 complex. We suggest that the effect might reflect the situation occurring in vivo as the homeostatic proliferation of otherwise non-stimulated, peripheral B lymphocytes, providing an always ready pool for efficient antibody production to any new (or cognate) antigen challenge. © The Japanese Society for Immunology. 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Mechanism of interleukin-13 production by granulocyte-macrophage colony-stimulating factor-dependent macrophages via protease-activated receptor-2.

Science.gov (United States)

Yamaguchi, Rui; Yamamoto, Takatoshi; Sakamoto, Arisa; Ishimaru, Yasuji; Narahara, Shinji; Sugiuchi, Hiroyuki; Hirose, Eiji; Yamaguchi, Yasuo

2015-06-01

Granulocyte-macrophage colony-stimulating factor (GM-CSF) promotes classically activated M1 macrophages. GM-CSF upregulates protease-activated receptor-2 (PAR-2) protein expression and activation of PAR-2 by human neutrophil elastase (HNE) regulates cytokine production. This study investigated the mechanism of PAR-2-mediated interleukin (IL)-13 production by GM-CSF-dependent macrophages stimulated with HNE. Adherent macrophages were obtained from primary cultures of human mononuclear cells. After stimulation with HNE to activate the mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) signaling pathway, IL-13 mRNA and protein levels were assessed by the reverse transcriptase-polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. PAR-2 protein was detected in GM-CSF-dependent macrophages by Western blotting. Unexpectedly, PD98059 (an ERK1 inhibitor) increased IL-13 production, even at higher concentrations. Interestingly, U0126 (an ERK1/2 inhibitor) reduced IL-13 production in a concentration-dependent manner. Neither SB203580 (a p38alpha/p38beta inhibitor) nor BIRB796 (a p38gamma/p38delta inhibitor) affected IL-13 production, while TMB-8 (a calcium chelator) diminished IL-13 production. Stimulation with HNE promoted the production of IL-13 (a Th2 cytokine) by GM-CSF-dependent M1 macrophages. PAR-2-mediated IL-13 production may be dependent on the Ca(2+)/ERK2 signaling pathway. Copyright © 2015 Elsevier Inc. All rights reserved.

TRPV2 mediates adrenomedullin stimulation of prostate and urothelial cancer cell adhesion, migration and invasion.

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Agathe Oulidi

Full Text Available Adrenomedullin (AM is a 52-amino acid peptide initially isolated from human pheochromocytoma. AM is expressed in a variety of malignant tissues and cancer cell lines and was shown to be a mitogenic factor capable of stimulating growth of several cancer cell types. In addition, AM is a survival factor for certain cancer cells. Some data suggest that AM might be involved in the progression cancer metastasis via angiogenesis and cell migration and invasion control. The Transient Receptor Potential channel TRPV2 is known to promote in prostate cancer cell migration and invasive phenotype and is correlated with the stage and grade of bladder cancer. In this work we show that AM induces prostate and urothelial cancer cell migration and invasion through TRPV2 translocation to plasma membrane and the subsequent increase in resting calcium level.

A single point mutation changes the crystallization behavior of Mycoplasma arthritidis-derived mitogen

Energy Technology Data Exchange (ETDEWEB)

Guo, Yi; Li, Zhong; Van Vranken, Sandra J. [Wadsworth Center, New York State Department of Health, Empire State Plaza, PO Box 509, Albany, New York 12201-0509 (United States); Li, Hongmin, E-mail: lih@wadsworth.org [Wadsworth Center, New York State Department of Health, Empire State Plaza, PO Box 509, Albany, New York 12201-0509 (United States); Department of Biomedical Sciences, School of Public Health, University at Albany, State University of New York, Empire State Plaza, PO Box 509, Albany, New York 12201-0509 (United States)

2006-03-01

The mutagenesis, crystallization and preliminary crystallographic analysis of M. arthritidis-derived mitogen is described. Mycoplasma arthritidis-derived mitogen (MAM) functions as a conventional superantigen (SAg). Although recombinant MAM has been crystallized by the hanging-drop vapour-diffusion method, the crystals diffracted poorly to only 5.0 Å resolution, with large unit-cell parameters a = 163.8, b = 93.0, c = 210.9 Å, β = 93.7° in the monoclinic space group P2{sub 1}. Unit-cell content analysis revealed that as many as 24 molecules could be present in the asymmetric unit. Systematic alanine mutagenesis was applied in order to search for mutants that give crystals of better quality. Two mutants, L50A and K201A, were crystallized under the same conditions as wild-type MAM (MAM{sub wt}). Crystals of the L50A mutant are isomorphous with those of MAM{sub wt}, while a new crystal form was obtained for the K201 mutant, belonging to the cubic space group P4{sub 1}32 with unit-cell parameters a = b = c = 181.9 Å. Diffraction data were collected to 3.6 and 2.8 Å resolution from crystals of the MAM L50A and K201A mutants, respectively. Molecular-replacement calculations suggest the presence of two molecules in the asymmetric unit for the MAM K201A mutant crystal, resulting in a V{sub M} of 5.0 Å Da{sup −1} and a solvent content of 75%. An interpretable electron-density map for the MAM K201A mutant crystal was produced using the molecular-replacement method.

Sirtuin inhibition attenuates the production of inflammatory cytokines in lipopolysaccharide-stimulated macrophages

Energy Technology Data Exchange (ETDEWEB)

Fernandes, Claudia A. [Universite catholique de Louvain, Louvain Drug Research Institute (LDRI), Pharmaceutics and Drug Delivery Research Group, Brussels B-1200 (Belgium); Fievez, Laurence [University of Liege, GIGA-Research, Laboratory of Cellular and Molecular Immunology, Liege B-4000 (Belgium); Neyrinck, Audrey M.; Delzenne, Nathalie M. [Universite catholique de Louvain, LDRI, Metabolism and Nutrition Research Group, Brussels B-1200 (Belgium); Bureau, Fabrice [University of Liege, GIGA-Research, Laboratory of Cellular and Molecular Immunology, Liege B-4000 (Belgium); Vanbever, Rita, E-mail: rita.vanbever@uclouvain.be [Universite catholique de Louvain, Louvain Drug Research Institute (LDRI), Pharmaceutics and Drug Delivery Research Group, Brussels B-1200 (Belgium)

2012-04-20

Highlights: Black-Right-Pointing-Pointer Lipopolysaccharide-stimulated macrophages were treated with cambinol and sirtinol. Black-Right-Pointing-Pointer Cambinol and sirtinol decreased lipopolysaccharide-induced cytokines. Black-Right-Pointing-Pointer Cambinol decreased NF-{kappa}B activity but had no impact on p38 MAPK activation. Black-Right-Pointing-Pointer Sirtuins are an interesting target for the treatment of inflammatory diseases. -- Abstract: In several inflammatory conditions such as rheumatoid arthritis or sepsis, the regulatory mechanisms of inflammation are inefficient and the excessive inflammatory response leads to damage to the host. Sirtuins are class III histone deacetylases that modulate the activity of several transcription factors that are implicated in immune responses. In this study, we evaluated the impact of sirtuin inhibition on the activation of lipopolysaccharide (LPS)-stimulated J774 macrophages by assessing the production of inflammatory cytokines. The pharmacologic inhibition of sirtuins decreased the production of tumour necrosis factor-alpha (TNF-{alpha}) interleukin 6 (IL-6) and Rantes. The reduction of cytokine production was associated with decreased nuclear factor kappa B (NF-{kappa}B) activity and inhibitor kappa B alpha (I{kappa}B{alpha}) phosphorylation while no impact was observed on the phosphorylation status of p38 mitogen-activated kinase (p38 MAPK). This work shows that sirtuin pharmacologic inhibitors are a promising tool for the treatment of inflammatory conditions.

Rapid lymphocyte immunoreactivity test utilizing [3H]uridine in vitro

International Nuclear Information System (INIS)

Pienkowski, M.M.; Lyerly, M.M.; Miller, H.C.

1978-01-01

A microculture assay utilizing [ 3 H]uridine incorporation was developed to test murine spleen lymphocyte immunoreactivity in vitro. Parameters of the culture technique which included cell density, doses of LPS, Con A, PHA, [ 3 H]uridine levels, and length of culture time were investigated. Responses were detectable at 4 h for all 3 mitogens, with labelling ranging up to 180% of the control value. By 8 h there was a 200-350% increase in mitogen-induced incorporation of radioactivity. Similar increases were observed in a serum-free system. The responses were the result of increased incorporation of label by stimulated cultures rather than decreased labeling of non-mitogen treated cultures over time. The [ 3 H]uridine incorporation was demonstrated to be the selective response of T or B cell populations when stimulated with appropriate lectins. This assay detects early RNA synthesis, as supported by experimental observations in which accumulation of radioactivity in stimulated lymphocytes was TCA precipitable, resistant to SDS treatment, and inhibited by actinomycin D. (Auth.)

Subpopulations of lymphocytes and their bearing on the radiation dose-response of the human lymphocyte (cell survival, mitogenic stimulation and chromosome aberration frequency)

International Nuclear Information System (INIS)

Schwartz, J.L.

1979-01-01

To determine whether in the lymphocyte the frequency of chromosome aberrations might be influenced by a differential radiation response of the varying types of cells, as well as interactions among them, subpopulations were separated on the basis of differences in cell surface receptors. The subpopulations, namely, T and B lymphocytes and three T subsets, T-M, T-G, T-null, were found to differ in radiosensitivity as measured by survival in culture and mitotic index after PHA stimulation. All the populations studied are represented to varying degrees among the mitotic cells of unirradiated samples 48 hours after PHA stimulation. At increasing doses of 6 Co gamma rays (50, 100, 250, 500 rads), however, their proportions change both as a direct result of irradiation, such as cell killing, and as an indirect effect, such as the reduction in suppressor cell action

Pretreatment with oleic acid accelerates the entrance into the mitotic cycle of EGF-stimulated fibroblasts.

Science.gov (United States)

Zugaza, J L; Casabiell, X A; Bokser, L; Eiras, A; Beiras, A; Casanueva, F F

1995-07-01

We have previously demonstrated that pretreatment of several cell lines with cis-unsaturated fatty acids, like oleic acid, blocks epidermal growth factor (EGF)-induced early ionic signals, and in particular the [Ca2+]i rise. In the present work we show that this blockade does not alter EGF-stimulated cellular proliferation evaluated by direct cell counting, but induces a powerful enhancement in the pulsed thymidine incorporation assay. The lack of effect of oleic acid on EGF-stimulated cellular proliferation was confirmed by repeated cell counts, cumulative thymidine incorporation, and protein synthesis, but a clear synergistic effect between oleic acid and EGF was again obtained by means of time course experiments with pulsed thymidine. Combined flow cytometry analysis and cell counts at earlier times in EGF-stimulated cells showed that oleic acids accelerates the entrance of cells into the replicative cycle leading to an earlier cell division. Afterward, these oleic acid-pretreated cells became delayed by an unknown compensatory mechanism in such a way that at 48 h post-EGF, the cell count in control and oleic acid-pretreated cells was equal. In conclusion (a) oleic acid accelerates or enhances the EGF mitogenic action and (b) in the long term cells compensate the initial perturbation with respect to untreated cells. As a side observation, the widely employed pulsed thymidine incorporation method as a measure of cell division could be extremely misleading unless experimental conditions are well controlled.

Aloin Inhibits Interleukin (IL)-1β-Stimulated IL-8 Production in KB Cells.

Science.gov (United States)

Na, Hee Sam; Song, Yu Ri; Kim, Seyeon; Heo, Jun-Young; Chung, Hae-Young; Chung, Jin

2016-06-01

Interleukin (IL)-1β, which is elevated in oral diseases including gingivitis, stimulates epithelial cells to produce IL-8 and perpetuate inflammatory responses. This study investigates stimulatory effects of salivary IL-1β in IL-8 production and determines if aloin inhibits IL-1β-stimulated IL-8 production in epithelial cells. Saliva was collected from volunteers to determine IL-1β and IL-8 levels. Samples from volunteers were divided into two groups: those with low and those with high IL-1β levels. KB cells were stimulated with IL-1β or saliva with or without IL-1 receptor agonist or specific mitogen-activated protein kinase (MAPK) inhibitors. IL-8 production was measured by enzyme-linked immunosorbent assay (ELISA). MAPK protein expression involved in IL-1β-induced IL-8 secretion was detected by Western blot. KB cells were pretreated with aloin, and its effect on IL-1β-induced IL-8 production was examined by ELISA and Western blot analysis. Saliva with high IL-1β strongly stimulated IL-8 production in KB cells, and IL-1 receptor agonist significantly inhibited IL-8 production. Low IL-1β-containing saliva did not increase IL-8 production. IL-1β treatment of KB cells induced activation of MAPK signaling molecules as well as nuclear factor-kappa B. IL-1β-induced IL-8 production was decreased by p38 and extracellular signal-regulated kinase (ERK) inhibitor treatment. Aloin pretreatment inhibited IL-1β-induced IL-8 production in a dose-dependent manner and inhibited activation of the p38 and ERK signaling pathway. Finally, aloin pretreatment also inhibited saliva-induced IL-8 production. Results indicated that IL-1β in saliva stimulates epithelial cells to produce IL-8 and that aloin effectively inhibits salivary IL-1β-induced IL-8 production by mitigating the p38 and ERK pathway. Therefore, aloin may be a good candidate for modulating oral inflammatory diseases.

Anti-inflammatory effects of ursodeoxycholic acid by lipopolysaccharide-stimulated inflammatory responses in RAW 264.7 macrophages.

Directory of Open Access Journals (Sweden)

Wan-Kyu Ko

Full Text Available The aim of this study was to investigate the anti-inflammatory effects of Ursodeoxycholic acid (UDCA in lipopolysaccharide (LPS-stimulated RAW 264.7 macrophages.We induced an inflammatory process in RAW 264.7 macrophages using LPS. The anti-inflammatory effects of UDCA on LPS-stimulated RAW 264.7 macrophages were analyzed using nitric oxide (NO. Pro-inflammatory and anti-inflammatory cytokines were analyzed by quantitative real time polymerase chain reaction (qRT-PCR and enzyme-linked immunosorbent assay (ELISA. The phosphorylations of extracellular signal-regulated kinase (ERK, c-Jun N-terminal kinase (JNK, and p38 in mitogen-activated protein kinase (MAPK signaling pathways and nuclear factor kappa-light polypeptide gene enhancer in B-cells inhibitor, alpha (IκBα signaling pathways were evaluated by western blot assays.UDCA decreased the LPS-stimulated release of the inflammatory mediator NO. UDCA also decreased the pro-inflammatory cytokines tumor necrosis factor-α (TNF-α, interleukin 1-α (IL-1α, interleukin 1-β (IL-1β, and interleukin 6 (IL-6 in mRNA and protein levels. In addition, UDCA increased an anti-inflammatory cytokine interleukin 10 (IL-10 in the LPS-stimulated RAW 264.7 macrophages. UDCA inhibited the expression of inflammatory transcription factor nuclear factor kappa B (NF-κB in LPS-stimulated RAW 264.7 macrophages. Furthermore, UDCA suppressed the phosphorylation of ERK, JNK, and p38 signals related to inflammatory pathways. In addition, the phosphorylation of IκBα, the inhibitor of NF-κB, also inhibited by UDCA.UDCA inhibits the pro-inflammatory responses by LPS in RAW 264.7 macrophages. UDCA also suppresses the phosphorylation by LPS on ERK, JNK, and p38 in MAPKs and NF-κB pathway. These results suggest that UDCA can serve as a useful anti-inflammatory drug.

Anti-inflammatory effects of progesterone in lipopolysaccharide-stimulated BV-2 microglia.

Directory of Open Access Journals (Sweden)

Beilei Lei

Full Text Available Female sex is associated with improved outcome in experimental brain injury models, such as traumatic brain injury, ischemic stroke, and intracerebral hemorrhage. This implies female gonadal steroids may be neuroprotective. A mechanism for this may involve modulation of post-injury neuroinflammation. As the resident immunomodulatory cells in central nervous system, microglia are activated during acute brain injury and produce inflammatory mediators which contribute to secondary injury including proinflammatory cytokines, and nitric oxide (NO and prostaglandin E2 (PGE2, mediated by inducible NO synthase (iNOS and cyclooxygenase-2 (COX-2, respectively. We hypothesized that female gonadal steroids reduce microglia mediated neuroinflammation. In this study, the progesterone's effects on tumor necrosis factor alpha (TNF-α, iNOS, and COX-2 expression were investigated in lipopolysaccharide (LPS-stimulated BV-2 microglia. Further, investigation included nuclear factor kappa B (NF-κB and mitogen activated protein kinase (MAPK pathways. LPS (30 ng/ml upregulated TNF-α, iNOS, and COX-2 protein expression in BV-2 cells. Progesterone pretreatment attenuated LPS-stimulated TNF-α, iNOS, and COX-2 expression in a dose-dependent fashion. Progesterone suppressed LPS-induced NF-κB activation by decreasing inhibitory κBα and NF-κB p65 phosphorylation and p65 nuclear translocation. Progesterone decreased LPS-mediated phosphorylation of p38, c-Jun N-terminal kinase and extracellular regulated kinase MAPKs. These progesterone effects were inhibited by its antagonist mifepristone. In conclusion, progesterone exhibits pleiotropic anti-inflammatory effects in LPS-stimulated BV-2 microglia by down-regulating proinflammatory mediators corresponding to suppression of NF-κB and MAPK activation. This suggests progesterone may be used as a potential neurotherapeutic to treat inflammatory components of acute brain injury.

Initiation-promotion skin carcinogenesis and immunological competence.

Science.gov (United States)

Curtis, G L; Stenbäck, F; Ryan, W L

1975-10-01

The immune competence of mice during initiation-promotion skin carcinogenesis was determined by skin allograft rejection and lymphocyte mitogenesis. The carcinogen 7, 12-dimethylbenzanthracene inhibited the cellular immune competence of mice while lymphocytes from croton oil treated mice had enhanced PWM response. Chlorphenesin, a stimulator of cellular immunity, was found to inhibit tumorigenesis in initiation-promotion skin carcinogenesis when injected during promotion.

Pentachlorophenol-Induced Cytotoxic, Mitogenic, and Endocrine-Disrupting Activities in Channel Catfish, Ictalurus punctatus

Directory of Open Access Journals (Sweden)

Paul B. Tchounwou

2004-09-01

Full Text Available Pentachlorophenol (PCP is an organochlorine compound that has been widely used as a biocide in several industrial, agricultural, and domestic applications. Although it has been shown to induce systemic toxicity and carcinogenesis in several experimental studies, the literature is scarce regarding its toxic mechanisms of action at the cellular and molecular levels. Recent investigations in our laboratory have shown that PCP induces cytotoxicity and transcriptionally activates stress genes in human liver carcinoma (HepG2 cells [1]. In this research, we hypothesize that environmental exposure to PCP may trigger cytotoxic, mitogenic, and endocrine-disrupting activities in aquatic organisms including fish. To test this hypothesis, we carried out in vitro cultures of male channel catfish hepatocytes, and performed the fluorescein diacetate assay (FDA to assess for cell viability, and the Western Blot analysis to assess for vitellogenin expression following exposure to PCP. Data obtained from FDA experiments indicated a strong dose-response relationship with respect to PCP cytotoxicity. Upon 48 hrs of exposure, the chemical dose required to cause 50% reduction in cell viability (LD50 was computed to be 1,987.0 + 9.6 μg PCP/mL. The NOAEL and LOAEL were 62.5 + 10.3 μg PCP/mL and 125.0+15.2 μg PCP/mL, respectively. At lower levels of exposure, PCP was found to be mitogenic, showing a strong dose- and time-dependent response with regard to cell proliferation. Western Blot analysis demonstrated the potential of PCP to cause endocrine-disrupting activity, as evidenced by the up regulation of the 125-kDa vitellogenin protein the hepatocytes of male channel catfish.

Effect of radiotherapy on the immunocompetence in patients with bronchogenic carcinoma and laryngeal cancer

International Nuclear Information System (INIS)

Oshitani, Takashi

1981-01-01

We evaluated the immunocompetence of 80 patients with bronchogenic carcinoma and 17 patients with laryngeal cancer undergoing radiotherapy, using collectively many types of immunological parameters. In patients with bronchogenic carcinoma, no significant difference was seen with PHA and PPD skin tests, but the reactivity of PHA skin tests gradually decreased in the course of treatment. It was assumed that radiotherapy might not interfere with the recognition of antigen. Lymphocyte blastoid transformations with PHA, Con A and PWM were all inhibited significantly. Since these three mitogens can stimulate the different groups of lymphocyte, the inhibition to the proliferative function of lymphocyte due to radiotherapy would seem to cover a wide area, including T and B lymphocyte. Concerning the comparative radiosensitivity of T and B lymphocyte, no significant result was obtained. However, in the dose of 20Gy the percentage of T lymphocyte decreased, while the percentage of B lymphocyte increased. The percentage of early rosetts, one subset of T cell, decreased more sensitively than that of T cell, but there was no significant difference. Immunocompetence of cases in stage III, which was significantly high before treatment, decreased to the same level as those in stage IV according to the treatment. In patients with laryngeal cancer, lymphocyte counts and reactivity of PHA skin tests were not influenced by radiotherapy, and then reactivity of PPD skin tests and lymphocyte blastoid transformations with PHA and Con A tended to increase instead. (J.P.N.)

Down-Regulation by Resveratrol of Basic Fibroblast Growth Factor-Stimulated Osteoprotegerin Synthesis through Suppression of Akt in Osteoblasts

Directory of Open Access Journals (Sweden)

Gen Kuroyanagi

2014-10-01

Full Text Available It is firmly established that resveratrol, a natural food compound abundantly found in grape skins and red wine, has beneficial properties for human health. In the present study, we investigated the effect of basic fibroblast growth factor (FGF-2 on osteoprotegerin (OPG synthesis in osteoblast-like MC3T3-E1 cells and whether resveratrol affects the OPG synthesis. FGF-2 stimulated both the OPG release and the expression of OPG mRNA. Resveratrol significantly suppressed the FGF-2-stimulated OPG release and the mRNA levels of OPG. SRT1720, an activator of SIRT1, reduced the FGF-2-induced OPG release and the OPG mRNA expression. PD98059, an inhibitor of upstream kinase activating p44/p42 mitogen-activated protein (MAP kinase, had little effect on the FGF-2-stimulated OPG release. On the other hand, SB203580, an inhibitor of p38 MAP kinase, SP600125, an inhibitor of stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK, and Akt inhibitor suppressed the OPG release induced by FGF-2. Resveratrol failed to affect the FGF-2-induced phosphorylation of p44/p42 MAP kinase, p38 MAP kinase or SAPK/JNK. The phosphorylation of Akt induced by FGF-2 was significantly suppressed by resveratrol or SRT1720. These findings strongly suggest that resveratrol down-regulates FGF-2-stimulated OPG synthesis through the suppression of the Akt pathway in osteoblasts and that the inhibitory effect of resveratrol is mediated at least in part by SIRT1 activation.

Mitogen-Activated Protein Kinase Phosphatase-2 Deletion Impairs Synaptic Plasticity and Hippocampal-Dependent Memory.

Science.gov (United States)

Abdul Rahman, Nor Zaihana; Greenwood, Sam M; Brett, Ros R; Tossell, Kyoko; Ungless, Mark A; Plevin, Robin; Bushell, Trevor J

2016-02-24

Mitogen-activated protein kinases (MAPKs) regulate brain function and their dysfunction is implicated in a number of brain disorders, including Alzheimer's disease. Thus, there is great interest in understanding the signaling systems that control MAPK function. One family of proteins that contribute to this process, the mitogen-activated protein kinase phosphatases (MKPs), directly inactivate MAPKs through dephosphorylation. Recent studies have identified novel functions of MKPs in development, the immune system, and cancer. However, a significant gap in our knowledge remains in relation to their role in brain functioning. Here, using transgenic mice where the Dusp4 gene encoding MKP-2 has been knocked out (MKP-2(-/-) mice), we show that long-term potentiation is impaired in MKP-2(-/-) mice compared with MKP-2(+/+) controls whereas neuronal excitability, evoked synaptic transmission, and paired-pulse facilitation remain unaltered. Furthermore, spontaneous EPSC (sEPSC) frequency was increased in acute slices and primary hippocampal cultures prepared from MKP-2(-/-) mice with no effect on EPSC amplitude observed. An increase in synapse number was evident in primary hippocampal cultures, which may account for the increase in sEPSC frequency. In addition, no change in ERK activity was detected in both brain tissue and primary hippocampal cultures, suggesting that the effects of MKP-2 deletion were MAPK independent. Consistent with these alterations in hippocampal function, MKP-2(-/-) mice show deficits in spatial reference and working memory when investigated using the Morris water maze. These data show that MKP-2 plays a role in regulating hippocampal function and that this effect may be independent of MAPK signaling. Copyright © 2016 Abdul Rahman et al.

Mechanism of the melanogenesis stimulation activity of (-)-cubebin in murine B16 melanoma cells.

Science.gov (United States)

Hirata, Noriko; Naruto, Shunsuke; Ohguchi, Kenji; Akao, Yukihiro; Nozawa, Yoshinori; Iinuma, Munekazu; Matsuda, Hideaki

2007-07-15

(-)-Cubebin showed a melanogenesis stimulation activity in a concentration-dependent manner in murine B16 melanoma cells without any significant effects on cell proliferation. Tyrosinase activity was increased at 24-72 h after addition of cubebin to B16 cells, and then intracellular melanin amount was increased at 48-96 h after the treatment. The expression levels of tyrosinase were time-dependently enhanced after the treatment with cubebin. At the same time, the expression levels of tyrosinase mRNA were also increased after addition of cubebin. Furthermore Western blot analysis revealed that cubebin elevated the level of phosphorylation of p38 mitogen-activated protein kinase (MAPK). SB203580, a selective inhibitor of p38 MAPK, completely blocked cubebin-induced expression of tyrosinase mRNA in B16 cells. These results suggested that cubebin increased melanogenesis in B16 cells through the enhancement of tyrosinase expression mediated by activation of p38 MAPK.

Hypoxia-Induced Mitogenic Factor (HIMF/FIZZ1/RELM?) Recruits Bone Marrow-Derived Cells to the Murine Pulmonary Vasculature

OpenAIRE

Angelini, Daniel J.; Su, Qingning; Kolosova, Irina A.; Fan, Chunling; Skinner, John T.; Yamaji-Kegan, Kazuyo; Collector, Michael; Sharkis, Saul J.; Johns, Roger A.

2010-01-01

Background Pulmonary hypertension (PH) is a disease of multiple etiologies with several common pathological features, including inflammation and pulmonary vascular remodeling. Recent evidence has suggested a potential role for the recruitment of bone marrow-derived (BMD) progenitor cells to this remodeling process. We recently demonstrated that hypoxia-induced mitogenic factor (HIMF/FIZZ1/RELM?) is chemotactic to murine bone marrow cells in vitro and involved in pulmonary vascular remodeling ...

Aspergillus nidulans Natural Product Biosynthesis Is Regulated by MpkB, a Putative Pheromone Response Mitogen-Activated Protein Kinase

International Nuclear Information System (INIS)

Atoui, A.; Bao, D.; Kaur, N.; Grayburn, W.S.; Calvo, A.M.

2008-01-01

The Aspergillus nidulans putative mitogen-activated protein kinase encoded by mpkB has a role in natural product biosynthesis. An mpkB mutant exhibited a decrease in sterigmatocystin gene expression and low mycotoxin levels. The mutation also affected the expression of genes involved in penicillin and terrequinone A synthesis. mpkB was necessary for normal expression of laeA, which has been found to regulate secondary metabolism gene clusters. (author)

Energy optimal control strategies for electro motors; low-cost and sensorless PWM-VSI based induction motor control. Vol. 1: Main report, appendix and annex

Energy Technology Data Exchange (ETDEWEB)

Abrahamsen, F

1998-02-01

When variable speed induction motor drives are used in applications that run at low load for long periods, energy can be saved by reducing the motor flux at low load. In this report the efficiency of 2.2 kW standard and high-efficiency motor drives are investigated experimentally with efficiency optimized and constant flux control, with sinusoidal and PWM voltage supply and with varying switching frequency. Steady-state motor models are developed and verified experimentally, and are used to analyze and develop efficiency optimizing control strategies. Four energy optimal control strategies are tested experimentally: cos({phi}) control, model-based control, off-line calculated airgap flux control and stator current/input power minimising search control. Their dynamical properties and their ability to reject load disturbances are analysed. Their ability to save energy is tested on a water pump system. For a typical predefined test-cycle the energy optimal control reduces the energy consumption with 10% compared with classical constant V/Hz control. (au)

Time-dependent enhancement of lymphocyte activation by mitogens after exposure to isolation or water scheduling.

Science.gov (United States)

Jessop, J J; Gale, K; Bayer, B M

1988-01-01

The effects of isolation and water scheduling on mitogen induced lymphocyte proliferation were investigated. Isolated rats were animals which had been raised in group-housed conditions and then transferred to individual cages with ad lib access to water for a 1 or 2 week period. Water scheduled rats were maintained in group housing (5 rats per cage) with ad lib access to food but with access to water for a single 30 minute session each day. Responses of these groups were compared to those of animals which had been continuously group-housed with ad lib access to food and water. No differences in lymphocyte responses to phytohemagglutinin (PHA) were found 1 week after exposure to isolation. However, after 2 weeks, splenic and blood T lymphocytes from isolated animals demonstrated an increased proliferative response to suboptimum and maximum concentrations of PHA. Splenic B lymphocyte responses to lipopolysaccharide (LPS) from isolated animals were also increased by 2- to 3-fold compared to group-housed controls. Two weeks of exposure of animals to daily water scheduling similarly increased the splenic lymphocyte proliferation. This increased responsiveness to PHA was not accompanied by a significant change in the sensitivity of the lymphocytes to PHA, in the total number of white blood cells, or the proportion of splenic T or T helper lymphocytes. Our results show that the increase in lymphocyte proliferation is time-dependent, requires greater than 1 week of exposure to isolation and is due to factors other than changes in sensitivity to mitogen or T lymphocyte number.

Design and implementation of predictive current control of three-phase PWM rectifier using space-vector modulation (SVM)

International Nuclear Information System (INIS)

Bouafia, Abdelouahab; Gaubert, Jean-Paul; Krim, Fateh

2010-01-01

This paper is concerned with the design and implementation of current control of three-phase PWM rectifier based on predictive control strategy. The proposed predictive current control technique operates with constant switching frequency, using space-vector modulation (SVM). The main goal of the designed current control scheme is to maintain the dc-bus voltage at the required level and to achieve the unity power factor (UPF) operation of the converter. For this purpose, two predictive current control algorithms, in the sense of deadbeat control, are developed for direct controlling input current vector of the converter in the stationary α-β and rotating d-q reference frame, respectively. For both predictive current control algorithms, at the beginning of each switching period, the required rectifier average voltage vector allowing the cancellation of both tracking errors of current vector components at the end of the switching period, is computed and applied during a predefined switching period by means of SVM. The main advantages of the proposed predictive current control are that no need to use hysteresis comparators or PI controllers in current control loops, and constant switching frequency. Finally, the developed predictive current control algorithms were tested both in simulations and experimentally, and illustrative results are presented here. Results have proven excellent performance in steady and transient states, and verify the validity of the proposed predictive current control which is compared to other control strategies.

Isolated PWM DC-AC SICAM with an active capacitive voltage clamp[Pulse Density Modulated; Pulse Width Modulation

Energy Technology Data Exchange (ETDEWEB)

Ljusev, P.

2004-03-15

In this report an isolated PWM DC-AC SICAM with an active capacitive voltage clamp is presented. AC-DC power supply is implemented in its simplest form: diode rectifier followed by a medium-size charge-storage capacitors and possibly with an EMC filter on the mains entrance. Isolation from the AC mains is achieved using a high frequency (HF) transformer, whose voltages are not audio-modulated. The latter simplifies the design and is expected to have many advantages over the approach where the transformer voltages are modulated in regards to the audio signal reference. Input stage is built as a DC-AC inverter (push-pull, half-bridge or a full-bridge) and operated with 50% duty cycle, with all the challenges to avoid transformer saturation and obtain symmetrical operation. On the secondary side the output section is implemented as rectifier+inverter AC-AC stage, i.e. a true bidirectional bridge, which operation is aimed towards amplification of the audio signal. In order to solve the problem with the commutation of the load current, a dead time between the incoming and outgoing bidirectional switch is implemented, while a capacitive voltage clamp is used to keep the induced overvoltage to reasonable levels. The energy stored in the clamping capacitor is not wasted as in the dissipative clamps, but is rather transferred back to the primary side for further processing using an auxiliary isolated single-switch converter, i.e. an active clamping technique is used. (au)

Review: Mitogen-Activated Protein kinases in nutritional signaling in Arabidopsis

KAUST Repository

Chardin, Camille; Schenk, Sebastian T.; Hirt, Heribert; Colcombet, Jean; Krapp, Anne

2017-01-01

Mitogen-Activated Protein Kinase (MAPK) cascades are functional modules widespread among eukaryotic organisms. In plants, these modules are encoded by large multigenic families and are involved in many biological processes ranging from stress responses to cellular differentiation and organ development. Furthermore, MAPK pathways are involved in the perception of environmental and physiological modifications. Interestingly, some MAPKs play a role in several signaling networks and could have an integrative function for the response of plants to their environment. In this review, we describe the classification of MAPKs and highlight some of their biochemical actions. We performed an in silico analysis of MAPK gene expression in response to nutrients supporting their involvement in nutritional signaling. While several MAPKs have been identified as players in sugar, nitrogen, phosphate, iron and potassium-related signaling pathways, their biochemical functions are yet mainly unknown. The integration of these regulatory cascades in the current understanding of nutrient signaling is discussed and potential new avenues for approaches toward plants with higher nutrient use efficiencies are evoked.

Review: Mitogen-Activated Protein kinases in nutritional signaling in Arabidopsis

KAUST Repository

Chardin, Camille

2017-04-14

Mitogen-Activated Protein Kinase (MAPK) cascades are functional modules widespread among eukaryotic organisms. In plants, these modules are encoded by large multigenic families and are involved in many biological processes ranging from stress responses to cellular differentiation and organ development. Furthermore, MAPK pathways are involved in the perception of environmental and physiological modifications. Interestingly, some MAPKs play a role in several signaling networks and could have an integrative function for the response of plants to their environment. In this review, we describe the classification of MAPKs and highlight some of their biochemical actions. We performed an in silico analysis of MAPK gene expression in response to nutrients supporting their involvement in nutritional signaling. While several MAPKs have been identified as players in sugar, nitrogen, phosphate, iron and potassium-related signaling pathways, their biochemical functions are yet mainly unknown. The integration of these regulatory cascades in the current understanding of nutrient signaling is discussed and potential new avenues for approaches toward plants with higher nutrient use efficiencies are evoked.

Induced Mitogenic Activity in AML-12 Mouse Hepatocytes Exposed to Low-dose Ultra-Wideband Electromagnetic Radiation

Directory of Open Access Journals (Sweden)

P. B. Tchounwou

2005-04-01

Full Text Available Ultra–wideband (UWB technology has increased with the use of various civilian and military applications. In the present study, we hypothesized that low-dose UWB electromagnetic radiation (UWBR could elicit a mitogenic effect in AML-12 mouse hepatocytes, in vitro. To test this hypothesis, we exposed AML-12 mouse hepatocytes, to UWBR in a specially constructed gigahertz transverse electromagnetic mode (GTEM cell. Cells were exposed to UWBR for 2 h at a temperature of 23°C, a pulse width of 10 ns, a repetition rate of 1 kHz, and field strength of 5-20 kV/m. UWB pulses were triggered by an external pulse generator for UWBR exposure but were not triggered for the sham exposure. We performed an MTT Assay to assess cell viability for UWBR-treated and sham-exposed hepatocytes. Data from viability studies indicated a time-related increase in hepatocytes at time intervals from 8-24 h post exposure. UWBR exerted a statistically significant (p < 0.05 dose-dependent response in cell viability in both serum-treated and serum free medium (SFM -treated hepatocytes. Western blot analysis of hepatocyte lysates demonstrated that cyclin A protein was induced in hepatocytes, suggesting that increased MTT activity after UWBR exposure was due to cell proliferation. This study indicates that UWBR has a mitogenic effect on AML-12 mouse hepatocytes and implicates a possible role for UWBR in hepatocarcinoma.

Mitigation of direct neurotoxic effects of lidocaine and amitriptyline by inhibition of p38 mitogen-activated protein kinase in vitro and in vivo

NARCIS (Netherlands)

Lirk, Philipp; Haller, Ingrid; Myers, Robert R.; Klimaschewski, Lars; Kau, Yi-Chuan; Hung, Yu-Chun; Gerner, Peter

2006-01-01

Local anesthetic-induced direct neurotoxicity (paresthesia, failure to regain normal sensory and motor function) is a potentially devastating complication of regional anesthesia. Local anesthetics activate the p38 mitogen-activated protein kinase (MAPK) system, which is involved in apoptotic cell

The immunodeficiency of bone marrow-transplanted patients. The effect of patient lymphocytes on the response of donor lymphocytes to mitogens and allogeneic cells

DEFF Research Database (Denmark)

Ødum, Niels; Hofmann, B; Platz, P

1985-01-01

Lymphocytes from patients after bone marrow transplantation (BMT) are in most cases predominantly of the Leu-2+ (cytotoxic/suppressor) phenotypes and are almost unresponsive to mitogens. In contrast, normal Leu-3+-depleted, Leu-2+-enriched lymphocyte suspensions retain approximately 50...

Enhanced Ig production by human peripheral lymphocytes induced by aggregated C1q

NARCIS (Netherlands)

Daha, M. R.; Klar, N.; Hoekzema, R.; van Es, L. A.

1990-01-01

Because B cells express receptors for C1q, we have investigated the role of C1q in the stimulation of B cells. When B cells were cultured in the presence of C1q that had been frozen, T cells, and suboptimal concentrations of PWM, there was a dose-dependent enhancement of IgM, IgG, and IgA by the B

Comparison of Anti-Inflammatory Effects of Flavonoid-Rich Common and Tartary Buckwheat Sprout Extracts in Lipopolysaccharide-Stimulated RAW 264.7 and Peritoneal Macrophages

Directory of Open Access Journals (Sweden)

Tae Gyu Nam

2017-01-01

Full Text Available Buckwheat sprouts have been widely consumed all around world due to their great abundance of bioactive compounds. In this study, the anti-inflammatory effects of flavonoid-rich common buckwheat sprout (CBS and tartary buckwheat sprout (TBS extracts were evaluated in lipopolysaccharide- (LPS- stimulated RAW 264.7 murine macrophages and primary peritoneal macrophages from male BALB/c mice. Based on the reversed-phase HPLC analysis, the major flavonoids in CBS were determined to be C-glycosylflavones (orientin, isoorientin, vitexin, and isovitexin, quercetin-3-O-robinobioside, and rutin, whereas TBS contained only high amounts of rutin. The TBS extract exhibited higher inhibitory activity as assessed by the production of proinflammatory mediators such as nitric oxide and cytokines including tumor necrosis factor-α, interleukin- (IL- 6, and IL-12 in LPS-stimulated RAW 264.7 macrophages than CBS extract. In addition, TBS extract suppressed nuclear factor-kappa B activation by preventing inhibitor kappa B-alpha degradation and mitogen-activated protein kinase phosphorylation in LPS-stimulated RAW 264.7 macrophages. Moreover, the TBS extract markedly reduced LPS-induced cytokine production in peritoneal macrophages. Taken together, these findings suggest that TBS extract can be a potential source of anti-inflammatory agents that may influence macrophage-mediated inflammatory disorders.

A technique for separation of canine lymphocytes and their use in the lymphocytotoxic, blastogenic, and rosette assys.

Science.gov (United States)

Whitacre, C C; Lang, R W

1975-01-01

When the techniques established for preparing lymphocytes from human blood were applied to canine blood, the resulting preparations were contaminated with significant numbers of other blood cells. A three-step technique is described here for the separation of canine lymphocytes from blood which eliminates most granulocytes, platelets, and erythrocytes. Defibrinated blood is incubated with iron particles to allow phagocytosis by granulocytes. When mixed with Plasmagel, erythrocytes and iron-containing granulocytes sediment rapidly, leaving a lymphocyte-rich supernate plasma which is recovered and banded by centrifugation on a Ficoll-Hypaque gradient. Any erythrocytes remaining in the lymphocyte suspension aspirated from the gradient are eliminated by hypotonic lysis and centrifugation. The resulting preparation, representing 30 per cent recovery of the circulating lymphocytes, contained 85 to 94 per cent lymphocytes with a cell viability of 99 per cent. The functional capacity of the lymphocyte preparation was tested in three assays: 1) lymphoblastic transformation using phytohemagglutinin and pokeweed mitogen, 2) E rosette formation with human erythrocytes showed a mean 5 per cent rosette forming lymphocytes, 3) antibody-mediated lymphocytotoxicity using a canine anti-lymphocyte serum showed titers reproducible within one tube dilution.

Immunoregulatory activities of human immunodeficiency virus (HIV) proteins: Effect of HIV recombinant and synthetic peptides on immunoglobulin synthesis and proliferative responses by normal lymphocytes

International Nuclear Information System (INIS)

Nair, M.P.N.; Pottathil, R.; Heimer, E.P.; Schwartz, S.A.

1988-01-01

Recombinant and synthetic peptides corresponding to envelope proteins of the human immunodeficiency virus (HIV) were examined for their effects on the activities of lymphocytes from normal donors in vitro. Although lymphocytes cultured with env-gag peptides produced significant amounts of IgG, addition of env-gag peptides to a pokeweed mitogen-induced B-cell activation system resulted in suppression of immunoglobulin synthesis by normal lymphocytes. Recombinant antigens, env-gag and env-80 dihydrofolate reductase (DHFR), produced a substantial proliferative response by peripheral blood mononuclear cells (PBMC) as determined by [ 3 H]thymidine incorporation. PBMC precultured with HIV synthetic peptide env 578-608 also manifested significant proliferative responses as compared to control cultures. CD3 + lymphocytes precultured with recombinant HIV antigens, env-gag and env-80 DHFR, and synthetic HIV peptide, env 487-511, showed moderate but significant proliferative responses. Both recombinant antigens and synthetic peptides also produced a dose-dependent stimulatory effect on proliferation by CD3 - lymphocytes. These studies demonstrate that recombinant and synthetic peptides of the HIV genome express immunoregulatory T- and B-cell epitopes. Identification of unique HIV epitopes with immunogenic and immunoregulatory activities is necessary for the development of an effective vaccine against HIV infection

Changes of the blood lymphocyte population following sup 32 P treatment for polycythemia vera

Energy Technology Data Exchange (ETDEWEB)

Blomgren, H.; Svedmyr, E. (Radiumhemmet Karolinska Hospital, Stockholm (Sweden)); Petrini, B.; Wasserman, J.; Stedingk, L.-V. von (The Stockholm County Council, Central Microbiological Laboratory, Stockholm (Sweden))

1990-01-01

Orally administrated NA{sub 2} {sup 32}PO{sub 4} mainly accumulates in bone marrow where it emits {beta}-particles which may damage cells. Previously, we showed that {sup 32}P treatment for polycythemia vera (PVC) increased the phytohemagglutinin reactivity and proportions of T cells in the blood. Now we have examined the effects of {sup 32}P treatment for PCV on natural killer (NK) and B-lymphocyte subsets which are considered to undergo their maturation in bone marrow. A mean isotope dose of 240 MBq given to 14 patients reduced the peripheral lymphocyte counts to 60% at 6 weeks. B cells and NK cells were reduced to the highest relative extent followed by HNK-1 cells and T cells. Although the proportion of NK cells was reduced to 50% there was no concomitant reduction of NK activity against K562 cells. Pokeweed mitogen-triggered secretion of IgM was significantly reduced, but not that of IgG or IgA. It is suggested that lymphocytes which mature in bone marrow may be affected to the highest extent by {sup 32}P treatment in PCV. (author).

Activation of human B lymphocytes. 8. Differential radiosensitivity of subpopulations of lymphoid cells involved in the polyclonally-induced PFC responses of peripheral blood B lymphocytes

Energy Technology Data Exchange (ETDEWEB)

Fauci, A S; Pratt, K R; Whalen, G [National Inst. of Allergy and Infectious Diseases, Bethesda, MD (USA)

1978-11-01

The differential effect of various doses of irradiation on subpopulations of human peripheral blood lymphoid cells involved in the pokeweed mitogen induced PFC response against sheep red blood cells was studied. The plaque forming B cells were quite sensitive to low doses of irradiation with complete suppression of responses at 300 to 500 rad. On the contrary, helper T-cell function was resistant to 2000 rad. Co-culture of irradiated T cells with autologous or allogeneic B cells resulted in marked enhancement of PFC responses consistent with the suppression of naturally occurring suppressor cells with a resulting pure helper effect. Irradiated T-cell-depleted suspensions failed to produce this effect as did heat killed T cells, whereas mitomycin C treated T cells gave effects similar to irradiated T cells. These findings are consistent with a lack of requirement of cell division for a T-cell helper effect and a requirement of mitosis or another irradiation sensitive, mitomycin C sensitive process for a T-suppressor cell effect. These studies have potential relevance in the evaluation of subpopulations of human lymphoid cells involved in antibody production in normal individuals and in disease states.

Heparin-Binding EGF-like Growth Factor (HB-EGF) stimulates the proliferation of Müller glia-derived progenitor cells in avian and murine retinas

Science.gov (United States)

Todd, Levi; Volkov, Leo I.; Zelinka, Chris; Squires, Natalie; Fischer, Andy J.

2015-01-01

Müller glia can be stimulated to de-differentiate, proliferate and form Müller glia-derived progenitor cells (MGPCs) that regenerate retinal neurons. In the zebrafish retina, Heparin-Binding EGF-like Growth Factor (HB-EGF) may be one of the key factors that stimulate the formation of proliferating MGPCs. Currently nothing is known about the influence of HB-EGF on the proliferative potential of Müller glia in retinas of birds and rodents. In the chick retina, we found that levels of both hb-egf and egf-receptor are rapidly and transiently up-regulated following NMDA-induced damage. Although intraocular injections of HB-EGF failed to stimulate cell-signaling or proliferation of Müller glia in normal retinas, HB-EGF stimulated proliferation of MGPCs in damaged retinas. By comparison, inhibition of the EGF-receptor (EGFR) decreased the proliferation of MGPCs in damaged retinas. HB-EGF failed to act synergistically with FGF2 to stimulate the formation of MGPCs in the undamaged retina and inhibition of EGF-receptor did not suppress FGF2-mediated formation of MGPCs. In the mouse retina, HB-EGF stimulated the proliferation of Müller glia following NMDA-induced damage. Furthermore, HB-EGF stimulated not only MAPK-signaling in Müller glia/MGPCs, but also activated mTor- and Jak/Stat-signaling. We propose that levels of expression of EGFR are rate-limiting to the responses of Müller glia to HB-EGF and the expression of EGFR can be induced by retinal damage, but not by FGF2-treatment. We conclude that HB-EGF is mitogenic to Müller glia in both chick and mouse retinas, and HB-EGF is an important player in the formation of MGPCs in damaged retinas. PMID:26500021

Design of an Internal Model Control strategy for single-phase grid-connected PWM inverters and its performance analysis with a non-linear local load and weak grid.

Science.gov (United States)

Chaves, Eric N; Coelho, Ernane A A; Carvalho, Henrique T M; Freitas, Luiz C G; Júnior, João B V; Freitas, Luiz C

2016-09-01

This paper presents the design of a controller based on Internal Model Control (IMC) applied to a grid-connected single-phase PWM inverter. The mathematical modeling of the inverter and the LCL output filter, used to project the 1-DOF IMC controller, is presented and the decoupling of grid voltage by a Feedforward strategy is analyzed. A Proportional - Resonant Controller (P+Res) was used for the control of the same plant in the running of experimental results, thus moving towards the discussion of differences regarding IMC and P+Res performances, which arrived at the evaluation of the proposed control strategy. The results are presented for typical conditions, for weak-grid and for non-linear local load, in order to verify the behavior of the controller against such situations. Copyright © 2016 ISA. Published by Elsevier Ltd. All rights reserved.

Uric acid stimulates proliferative pathways in vascular smooth muscle cells through the activation of p38 MAPK, p44/42 MAPK and PDGFRβ.

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Kırça, M; Oğuz, N; Çetin, A; Uzuner, F; Yeşilkaya, A

2017-04-01

Hyperuricemia and angiotensin II (Ang II) may have a pathogenetic role in the development of hypertension and atherosclerosis as well as cardiovascular disease (CVD) and its prognosis. The purpose of this study was to investigate whether uric acid can induce proliferative pathways of vascular smooth muscle cell (VSMC) that are thought to be responsible for the development of CVD. The phosphorylation of p38 mitogen-activated protein kinase (p38 MAPK), p44/42 mitogen-activated protein kinase (p44/42 MAPK) and platelet-derived growth factor receptor β (PDGFRβ) was measured by Elisa and Western blot techniques to determine the activation of proliferative pathways in primary cultured VSMCs from rat aorta. Results demonstrated that uric acid can stimulate p38 MAPK, p44/42 MAPK and PDGFRβ phosphorylation in a time- and concentration-dependent manner. Furthermore, treatment of VSMCs with the angiotensin II type I receptor (AT1R) inhibitor losartan suppressed p38 MAPK and p44/42 MAPK induction by uric acid. The stimulatory effect of uric acid on p38 MAPK was higher compared to that of Ang II. The results of this study show for the first time that uric acid-induced PDGFRβ phosphorylation plays a crucial role in the development of CVDs and that elevated uric acid levels could be a potential therapeutical target in CVD patients.

Protein tyrosine kinase and mitogen-activated protein kinase signalling pathways contribute to differences in heterophil-mediated innate immune responsiveness between two lines of broilers

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Protein tyrosine phosphorylation mediates signal transduction of cellular processes, with protein tyrosine kinases (PTKs) regulating virtually all signaling events. The mitogen-activated protein kinase (MAPK) super-family consists of three conserved pathways that convert receptor activation into ce...

Functional Roles of p38 Mitogen-Activated Protein Kinase in Macrophage-Mediated Inflammatory Responses

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Yanyan Yang

2014-01-01

Full Text Available Inflammation is a natural host defensive process that is largely regulated by macrophages during the innate immune response. Mitogen-activated protein kinases (MAPKs are proline-directed serine and threonine protein kinases that regulate many physiological and pathophysiological cell responses. p38 MAPKs are key MAPKs involved in the production of inflammatory mediators, including tumor necrosis factor-α (TNF-α and cyclooxygenase-2 (COX-2. p38 MAPK signaling plays an essential role in regulating cellular processes, especially inflammation. In this paper, we summarize the characteristics of p38 signaling in macrophage-mediated inflammation. In addition, we discuss the potential of using inhibitors targeting p38 expression in macrophages to treat inflammatory diseases.

Human trophoblast-derived hydrogen sulfide stimulates placental artery endothelial cell angiogenesis.

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Chen, Dong-Bao; Feng, Lin; Hodges, Jennifer K; Lechuga, Thomas J; Zhang, Honghai

2017-09-01

Endogenous hydrogen sulfide (H2S), mainly synthesized by cystathionine β-synthase (CBS) and cystathionine γ-lyase (CTH), has been implicated in regulating placental angiogenesis; however, the underlying mechanisms are unknown. This study was to test a hypothesis that trophoblasts synthesize H2S to promote placental angiogenesis. Human choriocarcinoma-derived BeWo cells expressed both CBS and CTH proteins, while the first trimester villous trophoblast-originated HTR-8/SVneo cells expressed CTH protein only. The H2S producing ability of BeWo cells was significantly inhibited by either inhibitors of CBS (carboxymethyl hydroxylamine hemihydrochloride, CHH) or CTH (β-cyano-L-alanine, BCA) and that in HTR-8/SVneo cells was inhibited by CHH only. H2S donors stimulated cell proliferation, migration, and tube formation in ovine placental artery endothelial cells (oFPAECs) as effectively as vascular endothelial growth factor. Co-culture with BeWo and HTR-8/SVneo cells stimulated oFPAEC migration, which was inhibited by CHH or BCA in BeWo but CHH only in HTR-8/SVneo cells. Primary human villous trophoblasts (HVT) were more potent than trophoblast cell lines in stimulating oFPAEC migration that was inhibited by CHH and CHH/BCA combination in accordance with its H2S synthesizing activity linked to CBS and CTH expression patterns. H2S donors activated endothelial nitric oxide synthase (NOS3), v-AKT murine thymoma viral oncogene homolog 1 (AKT1), and extracellular signal-activated kinase 1/2 (mitogen-activated protein kinase 3/1, MAPK3/1) in oFPAECs. H2S donor-induced NOS3 activation was blocked by AKT1 but not MAPK3/1 inhibition. In keeping with our previous studies showing a crucial role of AKT1, MAPK3/1, and NOS3/NO in placental angiogenesis, these data show that trophoblast-derived endogenous H2S stimulates placental angiogenesis, involving activation of AKT1, NOS3/NO, and MAPK3/1. © The Authors 2017. Published by Oxford University Press on behalf of Society for the Study

Toward a Comprehensive Phylogenetic Reconstruction of the Evolutionary History of Mitogen-Activated Protein Kinases in the Plant Kingdom

OpenAIRE

Janitza, Philipp; Ullrich, Kristian Karsten; Quint, Marcel

2012-01-01

The mitogen-activated protein kinase (MAPK) pathway is a three-tier signaling cascade that transmits cellular information from the plasma membrane to the cytoplasm where it triggers downstream responses. The MAPKs represent the last step in this cascade and are activated when both tyrosine and threonine residues in a conserved TxY motif are phosphorylated by MAPK kinases, which in turn are themselves activated by phosphorylation by MAPK kinase kinases. To understand the molecular evolution of...

Proliferative signaling initiated in ACTH receptors

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C.F.P. Lotfi

2000-10-01

Full Text Available This article reviews recent results of studies aiming to elucidate modes of integrating signals initiated in ACTH receptors and FGF2 receptors, within the network system of signal transduction found in Y1 adrenocortical cells. These modes of signal integration should be central to the mechanisms underlying the regulation of the G0->G1->S transition in the adrenal cell cycle. FGF2 elicits a strong mitogenic response in G0/G1-arrested Y1 adrenocortical cells, that includes a rapid and transient activation of extracellular signal-regulated kinases-mitogen-activated protein kinases (ERK-MAPK (2 to 10 min, b transcription activation of c-fos, c-jun and c-myc genes (10 to 30 min, c induction of c-Fos and c-Myc proteins by 1 h and cyclin D1 protein by 5 h, and d onset of DNA synthesis stimulation within 8 h. ACTH, itself a weak mitogen, interacts with FGF2 in a complex manner, blocking the FGF2 mitogenic response during the early and middle G1 phase, keeping ERK-MAPK activation and c-Fos and cyclin D1 induction at maximal levels, but post-transcriptionally inhibiting c-Myc expression. c-Fos and c-Jun proteins are mediators in both the strong and the weak mitogenic responses respectively triggered by FGF2 and ACTH. Induction of c-Fos and stimulation of DNA synthesis by ACTH are independent of PKA and are inhibited by the PKC inhibitor GF109203X. In addition, ACTH is a poor activator of ERK-MAPK, but c-Fos induction and DNA synthesis stimulation by ACTH are strongly inhibited by the inhibitor of MEK1 PD98059.

The mitogen-activated protein kinase (MAPK pathway: role in immune evasion by trypanosomatids

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Mercedes Carolina Soares-Silva

2016-02-01

Full Text Available Leishmania spp and Trypanosoma cruzi are the causative agents of leishmaniasis and Chagas' disease, respectively, two neglected tropical diseases that affect about 25 million people worldwide. These parasites belong to the family Trypanosomatidae and are both obligate intracellular parasites that manipulate host signaling pathways to establish the infection, and also subvert the host innate immune system. Mitogen-activated protein kinases (MAPKs are serine and threonine protein kinases, highly conserved in eukaryotes, and are involved in signal transduction pathways that are related to modulation of physiological and pathophysiological cell responses. This mini-review highlights the current knowledge about the mechanisms that Leishmania spp and T. cruzi have evolved to target host MAPK signaling pathway, highjack immune response, and in this manner, promote parasite maintenance in the host.

Gc protein-derived macrophage-activating factor (GcMAF) stimulates cAMP formation in human mononuclear cells and inhibits angiogenesis in chick embryo chorionallantoic membrane assay.

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Pacini, Stefania; Morucci, Gabriele; Punzi, Tiziana; Gulisano, Massimo; Ruggiero, Marco

2011-04-01

The effects of Gc protein-derived macrophage-activating factor (GcMAF) have been studied in cancer and other conditions where angiogenesis is deregulated. In this study, we demonstrate for the first time that the mitogenic response of human peripheral blood mononuclear cells (PBMCs) to GcMAF was associated with 3'-5'-cyclic adenosine monophosphate (cAMP) formation. The effect was dose dependent, and maximal stimulation was achieved using 0.1 ng/ml. Heparin inhibited the stimulatory effect of GcMAF on PBMCs. In addition, we demonstrate that GcMAF (1 ng/ml) inhibited prostaglandin E(1)- and human breast cancer cell-stimulated angiogenesis in chick embryo chorionallantoic membrane (CAM) assay. Finally, we tested different GcMAF preparations on CAM, and the assay proved to be a reliable, reproducible and inexpensive method to determine the relative potencies of different preparations and their stability; we observed that storage at room temperature for 15 days decreased GcMAF potency by about 50%. These data could prove useful for upcoming clinical trials on GcMAF.

Blockades of mitogen-activated protein kinase and calcineurin both change fibre-type markers in skeletal muscle culture

DEFF Research Database (Denmark)

Higginson, James; Wackerhage, Henning; Woods, Niall

2002-01-01

A and mitogen-activated protein kinase kinase (MEK1/2) blockade with U0126 upon myosin heavy chain (MHC) isoform mRNA levels and activities of metabolic enzymes after 1 day, 3 days and 7 days of treatment in primary cultures of spontaneously twitching rat skeletal muscle. U0126 treatment significantly decreased......Activation of either the calcineurin or the extracellular signal-regulated kinase (ERK1/2) pathway increases the percentage of slow fibres in vivo suggesting that both pathways can regulate fibre phenotypes in skeletal muscle. We investigated the effect of calcineurin blockade with cyclosporin...

Lymphocyte transformation response to pokeweed mitogen as a predictive marker for development of AIDS and AIDS related symptoms in homosexual men with HIV antibodies

DEFF Research Database (Denmark)

Hofmann, B; Lindhardt, B O; Gerstoft, J

1987-01-01

To identify factors that may predict the development of the acquired immune deficiency syndrome (AIDS) or AIDS related symptoms various immunological measurements were studied in a group of homosexual men attending screening clinics for AIDS in Copenhagen. Fifty seven men whose ratio of T helper...... lymphocytes to T suppressor lymphocytes (CD4:CD8 ratio) was less than 1.0 before the study began were included. Forty two were positive for antibody to the human immunodeficiency virus (HIV), of whom 38 were reinvestigated after a median observation period of 10 months. Among the seropositive men...

Methotrexate induces poly(ADP-ribose) polymerase-dependent, caspase 3-independent apoptosis in subsets of proliferating CD4+ T cells

DEFF Research Database (Denmark)

Nielsen, C H; Albertsen, L; Bendtzen, K

2007-01-01

The mechanism of action of methotrexate (MTX) in autoimmune diseases (AID) is unclear. A pro-apoptotic effect has been demonstrated in mitogen-stimulated peripheral blood mononuclear cells (PBMC), but studies employing conventional antigens have disputed a pro-apoptotic effect. CD4+ T helper (Th....... Exposure of CA-stimulated PBMC to MTX significantly increased their level of cleaved poly(ADP-ribose) polymerase (PARP), and a similar tendency was observed in TT-stimulated cells. Unlike CA and TT, the mitogen phytohaemagglutinin (PHA) induced proliferation of both CD4- and CD4+ T cells, and induced......) cells play a significant role in most AID. We therefore examined directly, by flow cytometry, the uptake of MTX by the T helper (Th) cells stimulated for 6 days with Candida albicans (CA) or tetanus toxoid (TT), and its consequences with respect to induction of apoptosis. While none of the resting Th...

Development and evaluation of an interferon gamma assay for the diagnosis of tuberculosis in red deer experimentally infected with Mycobacterium bovis.

Science.gov (United States)

Risalde, María Ángeles; Thomas, Jobin; Sevilla, Iker; Serrano, Miriam; Ortíz, Jose Antonio; Garrido, Joseba; Domínguez, Mercedes; Domínguez, Lucas; Gortázar, Christian; Ruíz-Fons, Jose Francisco

2017-11-16

Red deer (Cervus elaphus) is regarded as an epidemiologically relevant host for Mycobacterium bovis (M. bovis) and closely related members of the Mycobacterium tuberculosis complex that cause animal tuberculosis (TB). The standard antemortem screening test for the detection of TB in deer is the intradermal tuberculin skin test, but the detection of interferon-gamma (IFNγ) produced by white blood cells exposed to M. bovis antigens can be used as an alternative or supplemental assay in most TB eradication/control programs. This study aims to develop an in-house sandwich ELISA for deer IFNγ, based on the cross-reactivity of the antibodies to both cervid and bovine IFNγ, and to evaluate the potential of this assay to detect M. bovis-infected red deer in response to the in vitro stimulation of whole-blood cells with bovine purified protein derivative (bPPD), p22 protein complex derived from bPPD or using the specific tuberculous mycobacterial proteins ESAT-6/CFP-10, Rv3615c and Rv3020c. The positive control stimulant used in this study was pokeweed mitogen, which resulted in a consistent induction of IFNγ in samples from red deer, thus allowing the interpretation of the assay. The percentage of animals correctly classified by this technique as M. bovis non-infected was 100%. The detection of infected animals as positive was high and ranged widely depending upon the antigen and the cut-off value applied, as well as the time after infection. Our findings indicate that this protocol may serve as a reliable assay for the antemortem diagnosis of TB from the initial stage of M. bovis-infection, and may also be adequately sensitive. The suggested optimal antigens and cut-off are bPPD, p22 and the combination of ESAT-6/CFP-10 and Rv3020c with a 0.05 Δ optical density, which yielded a up to 100% correct classification of TB positive and negatve red deer under our experimental conditions. This technique will aid in TB testing of farmed and translocated deer. Future studies

An improved method on stimulated T-lymphocytes to functionally characterize novel and known LDLR mutations[S

Science.gov (United States)

Romano, Maria; Di Taranto, Maria Donata; Mirabelli, Peppino; D'Agostino, Maria Nicoletta; Iannuzzi, Arcangelo; Marotta, Gennaro; Gentile, Marco; Raia, Maddalena; Di Noto, Rosa; Del Vecchio, Luigi; Rubba, Paolo; Fortunato, Giuliana

2011-01-01

The main causes of familial hypercholesterolemia (FH) are mutations in LDL receptor (LDLR) gene. Functional studies are necessary to demonstrate the LDLR function impairment caused by mutations and would be useful as a diagnostic tool if they allow discrimination between FH patients and controls. In order to identify the best method to detect LDLR activity, we compared continuous Epstein-Barr virus (EBV)-transformed B-lymphocytes and mitogen stimulated T-lymphocytes. In addition, we characterized both novel and known mutations in the LDLR gene. T-lymphocytes and EBV-transformed B-lymphocytes were obtained from peripheral blood of 24 FH patients and 24 control subjects. Functional assays were performed by incubation with fluorescent LDL followed by flow cytometry analysis. Residual LDLR activity was calculated normalizing fluorescence for the mean fluorescence of controls. With stimulated T-lymphocytes we obtained a better discrimination capacity between controls and FH patients compared with EBV-transformed B-lymphocytes as demonstrated by receiver operating characteristic (ROC) curve analysis (the areas under the curve are 1.000 and 0.984 respectively; P < 0.0001 both). The characterization of LDLR activity through T-lymphocytes is more simple and faster than the use of EBV-transformed B-lymphocytes and allows a complete discrimination between controls and FH patients. Therefore the evaluation of residual LDLR activity could be helpful not only for mutation characterization but also for diagnostic purposes. PMID:21865347

T. B-cell subpopulation in patients with malignant diseases

International Nuclear Information System (INIS)

Ogawa, Motoyoshi; Goto, Tatsuhiko; Naruto, Mamiko.

1978-01-01

T, B cells in the peripheural blood of patients with malignant diseases were investigated. The percentages of T cells in patients with malignant lymphomas correlated to the extent of disease determined by clinical stagings of Ann Arbor's classification, in stages III and IV T-cells decreased to compare with those in stages I and II, while B-cells did not show any changes. Absolute numbers of lymphocytes, blastogenesis induced by PHA or PWM decreased remarkably during combination chemotherapies and during radiotherapy whereas the percentages of T-cells measuring in the same patients did not influenced consistently by these treatments. The DNA pattern of lymphocytes during treatments was examined by Flow-Microphotometry and the result suggested that those lymphocytes were damaged by treatments and subsequently they were refractory to the action of mitogens. The results indicate that selective timing needs between chemotherapy and immunotherapy. (auth.)

IL-29 Enhances CXCL10 Production in TNF-α-stimulated Human Oral Epithelial Cells.

Science.gov (United States)

Hosokawa, Yoshitaka; Hosokawa, Ikuko; Shindo, Satoru; Ozaki, Kazumi; Matsuo, Takashi

2017-08-01

Interleukin-29 (IL-29) is a cytokine belonging to the Type III interferon family. It was recently detected in the gingival crevicular fluid of periodontitis patients. However, the role of IL-29 in the pathogenesis of periodontal disease remains unknown. The aim of this study was to examine the effects of IL-29 on C-X-C motif chemokine ligand 10 (CXCL10) production in human oral epithelial cells. We measured CXCL10 production in TR146 cells, which is a human oral epithelial cell line, using an enzyme-linked immunosorbent assay. We used a Western blot analysis to detect IL-29 receptor expression and the phosphorylation levels of signal transduction molecules, including p38 mitogen-activated protein kinases (MAPK), signal transducer and activator of transcription 3 (STAT3), and nuclear factor (NF)- κB p65, in the TR146 cells. The TR146 cells expressed the IL-29 receptor. IL-29 induced CXCL10 production in the TR146 cells. IL-29 significantly enhanced CXCL10 production in tumor necrosis factor (TNF)-α-stimulated TR146 cells. The p38 MAPK, STAT3, and NF-κB pathways were found to be related to the IL-29-induced enhancement of CXCL10 production in TNF-α-stimulated TR146 cells. IL-29 promotes T helper 1-cell accumulation in periodontal lesions by inducing CXCL10 production in oral epithelial cells.

Lymphocytic subsets and low-dose exposure

International Nuclear Information System (INIS)

Tuschl, H.; Kovac, R.; Eybl, E.

1993-03-01

The present investigations proved the differential radiosensitivity of lymphocytic subpopulations: From in vivo and in vitro irradiations it may be followed that the most sensitive subset are CD8 positive suppressor T cells. CD4/CD8 ratios are increased both in peripheral blood and after mitogen stimulation of lymphocytes of exposed persons. The decrease in B cells is pronounced only at higher radiation doses. Though the rate of DNA synthesis after mitogen stimulation was reduced in some exposed persons, that was no general phenomenon. Especially after tritium exposure, the observed lymphopenia correlated with an increased stimulation by PHA and an increased rate of DNA synthesis in some probands. Thus the present investigations indicate that - despite an inhibition of some immune parameters by radioexposure - the body is able to maintain its immunological homoeostasis. (authors)

[Study of signal transduction pathway in the expression of inflammatory factors stimulated by lipopolysaccharides from Porphyromonas endodontalis in osteoblasts].

Science.gov (United States)

Yang, Di; Qiu, Li-hong; Li, Ren; Li, Zi-mu; Li, Chen

2010-04-01

To quantify the interleukin (IL)-1beta mRNA and IL-6 mRNA expression induced by lipopolysaccharides ([PS) extracted from Porphyromonoas endodontalis (P. endodontalis) in osteoblasts, and to relate P. endodontalis LPS to the bone resorptive pathogenesis in the lesions of chronic apical periodontitis. MG63 cells was pretreated with PD98059 or SB203580 for 1 h and then treated with P. endodontolis LPS for 6 h. The expression of IL-1beta mRNA and IL-6 mRNA were detected by reverse transcription polymerase chain reaction (RT-PCR) technique. The production of IL-1beta mRNA induced by P. endodontalis LPS decreased in osteoblasts pretreated with PD98059. Both of the production of IL-1beta mRNA and JL-6 mRNA induced by P. endodontalis LPS decreased in osteoblasts pretreated with SB203580. The synthesis of IL-1beta mRNA stimulated by Pendodontalis LPS in MG63 probably occur via extracellular signal-regulated kinase (ERK) 1/2 and p38 mitogen activated protein kinase (MAPK) signal transduction system. The synthesis of IL-6 mRNA stimulated by P.endodontalis LPS in MG63 probahly occur via p38MAPK signal transduction system.

Calmodulin protects cells from death under normal growth conditions and mitogenic starvation but plays a mediating role in cell death upon B-cell receptor stimulation

DEFF Research Database (Denmark)

Schmalzigaug, R; Ye, Q; Berchtold, M W

2001-01-01

stimulation of the B-cell receptor (BCR), the resting Ca2+ levels remain elevated after the initial transient in CaMII-/- cells. Despite higher Ca2+ resting levels, the CaMII-/- cells are partially protected from BCR induced apoptosis indicating that CaM plays a dual role in apoptotic processes....

T-cell subset alterations and lymphocyte responsiveness to mitogens and antigen during severe primary infection with HIV: a case series of seven consecutive HIV seroconverters

DEFF Research Database (Denmark)

Pedersen, C; Dickmeiss, E; Gaub, J

1990-01-01

Seven consecutive patients who presented with a severe acute mononucleosis-like illness associated with HIV seroconversion were evaluated by T-cell subset enumerations and measurements of lymphocyte transformation responses to mitogens and antigen during both their primary illness and a 1-year...

Extract of Polygala tenuifolia Alleviates Stress-Exacerbated Atopy-Like Skin Dermatitis through the Modulation of Protein Kinase A and p38 Mitogen-Activated Protein Kinase Signaling Pathway

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Bongjun Sur

2017-01-01

Full Text Available Atopic dermatitis (AD and stress create a vicious cycle: stress exacerbates atopic symptoms, and atopic disease elicits stress and anxiety. Targeting multiple pathways including stress and allergic inflammation is, therefore, important for treating AD. In this study, we investigated the remedial value of Polygala tenuifolia Willd. (PTW for treating immobilization (IMO stress-exacerbated atopy-like skin dermatitis and its underlying mechanism. Trimellitic anhydride (TMA was applied to dorsal skin for sensitization and subsequently both ears for eliciting T-cell-dependent contact hypersensitivity in mice, which underwent 2 h-IMO stress and PTW administration for the latter 6 and 9 days in the ear exposure period of TMA, respectively. To elicit in vitro degranulation of human mast cell line-1 (HMC-1, 10 µM substance P (SP and 200 nM corticotrophin-releasing factor (CRF were sequentially added with 48 h-interval. PTW extract (500 µg/mL was added 30 min before CRF treatment. IMO stress exacerbated TMA-induced scratching behavior by 252%, and increased their blood corticosterone levels by two-fold. Treatment with 250 mg/kg PTW significantly restored IMO stress-exacerbated scratching behavior and other indicators such as skin inflammation and water content, lymph node weights, and serum histamine and immunoglobulin E (lgE levels. Furthermore, it also reversed TMA-stimulated expression of tumor necrosis factor (TNF-α and interleukin (IL-4 mRNAs in ear tissues. PTW significantly inhibited SP/CRF-stimulated degranulation of HMC-1 cells, subsequent tryptase secretion, and protein kinase A (PKA activity. PTW also selectively inhibited p38 mitogen-activated protein kinase (MAPK phosphorylation in SP/CRF-treated HMC-1 cells. PTW significantly inhibited HMC-1 cell degranulation and alleviated IMO stress-exacerbated atopic dermatitis symptoms by modulating the PKA/p38 MAPK signaling pathway.

Lung-derived growth factors: possible paracrine effectors of fetal lung development

International Nuclear Information System (INIS)

Montes, A.M.

1985-01-01

A potential role for paracrine secretions in lung organogenesis has been hypothesized (Alescio and Piperno, 1957). These studies present direct support for the paracrine model by demonstrating the presence of locally produced mitogenic/maturational factors in fetal rat lung tissue. Conditioned serum free medium (CSFM) from nineteen-day fetal rat lung cultures was shown to contain several bioactive peptides as detected by 3 H-Thymidine incorporation into chick embryo and rat lung fibroblasts, as well as 14 C-choline incorporation into surfactant in mixed cell cultures. Using ion-exchange chromatography and Sephadex gel filtration, a partially purified mitogen, 11-III, was obtained. The partially purified 11-III stimulates mitosis in chick embryo fibroblasts and post-natal rat lung fibroblasts. Multiplication in fetal rat lung fibroblasts cultures is stimulated only when these are pre-incubated with a competence factor or unprocessed CSFM. This suggests the existence of an endogenously produced competence factor important in the regulation of fetal lung growth. Preparation 11-III does not possess surfactant stimulating activity as assessed by 3 H-choline incorporation into lipids in predominantly type-II cell cultures. These data demonstrate the presence of a maturational/mitogenic factor, influencing type-II mixed cell cultures. In addition, 11-III had been shown to play an autocrine role stimulating the proliferation of fetal lung fibroblasts. Finally, these data suggest the existence of a local produced competence factor

Development of microheaters for gas sensor with an AT-Mega 8535 temperature controller using a PWM (pulse width modulation) method

Science.gov (United States)

Megayanti, Meti; Panatarani, Camellia; Joni, I. Made

2016-03-01

Microheater is the main component in gas sensor characterized by their sensitivity, selectivity, and time response of gas sensor which is depend on the microheater temperature stability. A Cu microheater was developed and utilized AT-Mega 8535 controller using a PWM (pulse width modulation) method. This control system is interfaced to the PC to observe the real time temperature response of the microheater. Three initial resistance (R0) variations of microheater were developed in an open loop control system. The power characteristic of designed microheater depends on the specified microheater initial resistance. The smaller R0, the less power required to reach a temperature setting value. The developed microheater was designed to reach a temperature setting value of 250°C having resistance 0.531 Ω for 1.979 Watt and 0.265 Ω for 1.072 Watt respectively. The results of the investigation on the control performances shows microheater-control system achieved operating temperature up to 250°C. The response of the temperature control shows smallest R0 resulted in a high stability with short settling time, short delay time and small ripple for temperature setting values higher than 150°C. The obtained error of microheater temperature with R0 = 0.265 is 8.596 %. It is concluded that the developed microheater can be utilized as a component of a gas sensor.

Development of microheaters for gas sensor with an AT-Mega 8535 temperature controller using a PWM (pulse width modulation) method

Energy Technology Data Exchange (ETDEWEB)

Megayanti, Meti; Panatarani, Camellia; Joni, I. Made, E-mail: imadejoni@phys.unpad.ac.id [Instrumentation System and Functional Material Processing Laboratory, Department of Physics, Faculty of Mathematics and Natural Sciences, Universitas Padjadjaran Jalan Raya Bandung-Sumedang KM 21, Jatinangor 45363, West Java (Indonesia)

2016-03-11

Microheater is the main component in gas sensor characterized by their sensitivity, selectivity, and time response of gas sensor which is depend on the microheater temperature stability. A Cu microheater was developed and utilized AT-Mega 8535 controller using a PWM (pulse width modulation) method. This control system is interfaced to the PC to observe the real time temperature response of the microheater. Three initial resistance (R0) variations of microheater were developed in an open loop control system. The power characteristic of designed microheater depends on the specified microheater initial resistance. The smaller R0, the less power required to reach a temperature setting value. The developed microheater was designed to reach a temperature setting value of 250°C having resistance 0.531 Ω for 1.979 Watt and 0.265 Ω for 1.072 Watt respectively. The results of the investigation on the control performances shows microheater-control system achieved operating temperature up to 250°C. The response of the temperature control shows smallest R0 resulted in a high stability with short settling time, short delay time and small ripple for temperature setting values higher than 150°C. The obtained error of microheater temperature with R0 = 0.265 is 8.596 %. It is concluded that the developed microheater can be utilized as a component of a gas sensor.

Bacteroides fragilis Enterotoxin Induces Formation of Autophagosomes in Endothelial Cells but Interferes with Fusion with Lysosomes for Complete Autophagic Flux through a Mitogen-Activated Protein Kinase-, AP-1-, and C/EBP Homologous Protein-Dependent Pathway.

Science.gov (United States)

Ko, Su Hyuk; Jeon, Jong Ik; Myung, Hyun Soo; Kim, Young-Jeon; Kim, Jung Mogg

2017-10-01

Bacteroides fragilis enterotoxin (BFT), a virulence factor of enterotoxigenic B. fragilis (ETBF), plays an essential role in mucosal inflammation. Although autophagy contributes to the pathogenesis of diverse infectious diseases, little is known about autophagy in ETBF infection. This study was conducted to investigate the role of BFT in the autophagic process in endothelial cells (ECs). Stimulation of human umbilical vein ECs (HUVECs) with BFT increased light chain 3 protein II (LC3-II) conversion from LC3-I and protein expression of p62, Atg5, and Atg12. In addition, BFT-exposed ECs showed increased indices of autophagosomal fusion with lysosomes such as LC3-lysosome-associated protein 2 (LAMP2) colocalization and the percentage of red vesicles monitored by the expression of dual-tagged LC3B. BFT also upregulated expression of C/EBP homologous protein (CHOP), and inhibition of CHOP significantly increased indices of autophagosomal fusion with lysosomes. BFT activated an AP-1 transcription factor, in which suppression of AP-1 activity significantly downregulated CHOP and augmented autophagosomal fusion with lysosomes. Furthermore, suppression of Jun N-terminal protein kinase (JNK) mitogen-activated protein kinase (MAPK) significantly inhibited the AP-1 and CHOP signals, leading to an increase in autophagosomal fusion with lysosomes in BFT-stimulated ECs. These results suggest that BFT induced accumulation of autophagosomes in ECs, but activation of a signaling pathway involving JNK, AP-1, and CHOP may interfere with complete autophagy. Copyright © 2017 American Society for Microbiology.

Residual activation events functional after irradiation of mouse splenic lymphocytes

International Nuclear Information System (INIS)

Duncan, D.D.; Lawrence, D.A.

1991-01-01

We have sought to identify the radiosensitivity of lymphocytes by determining the extent of activation of mitogen-stimulated lymphocytes previously exposed to growth-inhibiting doses of radiation. Mouse splenic lymphocytes were exposed to 0-15 Gy 137Cs radiation, and structural and functional damage were assayed. Although damage to cellular thiols and nonprotein thiols was modest, there was a significant loss of viability by 6 h as determined by uptake of propidium iodide (PI). Since cells did not die immediately after irradiation, the activation events which remained were evaluated. Growth-inhibiting doses of radiation left cells partially responsive to mitogen, in that cells were able to exit G0 phase, but they could progress no further into the cell cycle than G1a phase. It is important to note that assessment of viability by uptake of PI indicated substantial cell death after 15 Gy (45%, 6 h; 90%, 24 h); however, cell cycle analysis at 24 h indicated no significant decrease in progression from G0 to G1a phase. The LPS-stimulated response of B cells was more radiosensitive than the Con A-stimulated response of T cells. Further analysis of the Con A response indicated that production of interleukin-2 (IL-2) was unaffected, but expression of the IL-2 receptor was inhibited. Inhibition of poly-ADP-ribosylation and damage to lipids did not prevent the lack of mitogen responsiveness, since neither the ADP-ribose transferase inhibitor 3-aminobenzamide nor lipid radical scavengers had restorative effects on the mitogenic response. Nor was Con A-stimulated incorporation of [3H]thymidine restored with inhibitors of prostaglandin or leukotriene synthesis, suggesting that inhibition was due to direct effects on the Con A responders, and not indirect effects mediated by arachidonate metabolites

PI3 kinase is important for Ras, MEK and Erk activation of Epo-stimulated human erythroid progenitors

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Schmidt Enrico K

2004-05-01

Full Text Available Abstract Background Erythropoietin is a multifunctional cytokine which regulates the number of erythrocytes circulating in mammalian blood. This is crucial in order to maintain an appropriate oxygen supply throughout the body. Stimulation of primary human erythroid progenitors (PEPs with erythropoietin (Epo leads to the activation of the mitogenic kinases (MEKs and Erks. How this is accomplished mechanistically remained unclear. Results Biochemical studies with human cord blood-derived PEPs now show that Ras and the class Ib enzyme of the phosphatidylinositol-3 kinase (PI3K family, PI3K gamma, are activated in response to minimal Epo concentrations. Surprisingly, three structurally different PI3K inhibitors block Ras, MEK and Erk activation in PEPs by Epo. Furthermore, Erk activation in PEPs is insensitive to the inhibition of Raf kinases but suppressed upon PKC inhibition. In contrast, Erk activation induced by stem cell factor, which activates c-Kit in the same cells, is sensitive to Raf inhibition and insensitive to PI3K and PKC inhibitors. Conclusions These unexpected findings contrast with previous results in human primary cells using Epo at supraphysiological concentrations and open new doors to eventually understanding how low Epo concentrations mediate the moderate proliferation of erythroid progenitors under homeostatic blood oxygen levels. They indicate that the basal activation of MEKs and Erks in PEPs by minimal concentrations of Epo does not occur through the classical cascade Shc/Grb2/Sos/Ras/Raf/MEK/Erk. Instead, MEKs and Erks are signal mediators of PI3K, probably the recently described PI3K gamma, through a Raf-independent signaling pathway which requires PKC activity. It is likely that higher concentrations of Epo that are induced by hypoxia, for example, following blood loss, lead to additional mitogenic signals which greatly accelerate erythroid progenitor proliferation.

Growth hormone-releasing factor stimulates proliferation of somatotrophs in vitro

DEFF Research Database (Denmark)

Billestrup, Nils; Swanson, L W; Vale, W

1986-01-01

The mitogenic effect of the hypothalamic peptides growth hormone-releasing factor (GRF) and somatostatin on cultured growth hormone (GH)-producing cells (somatotrophs) was studied. Using autoradiographic detection of [3H]thymidine uptake and immunocytochemical identification of GH-producing cells...

An Algebraic Method of Synchronous Pulsewidth Modulation for Converters for Adjustable Speed Drives

DEFF Research Database (Denmark)

Oleschuk, Valentin; Blaabjerg, Frede

2002-01-01

This paper describes the basic peculiarities of a new method of feedforward synchronous pulsewidth modulation (PWM) of the output voltage of converters, based on one-stage closed-form strategy of PWM with pure algebraic control dependencies. It is applied to voltage source inverters with a contin......This paper describes the basic peculiarities of a new method of feedforward synchronous pulsewidth modulation (PWM) of the output voltage of converters, based on one-stage closed-form strategy of PWM with pure algebraic control dependencies. It is applied to voltage source inverters...... with a continuous scheme of conventional voltage space vector modulation and with two basic variants of symmetrical discontinuous PWM. Simulations give the behaviour of the proposed method and show the advantage of algebraic synchronous PWM compared with the typical asynchronous, for low indices of the frequency...

Induction of CD4 suppressor T cells with anti-Leu-8 antibody

International Nuclear Information System (INIS)

Kanof, M.E.; Strober, W.; James, S.P.

1987-01-01

To characterize the conditions under which CD4 T cells suppress polyclonal immunoglobulin synthesis, we investigated the capacity of CD4 T cells that coexpress the surface antigen recognized by the monoclonal antibody anti-Leu-8 to mediate suppression. In an in vitro system devoid of CD8 T cells, CD4, Leu-8+ T cells suppressed pokeweed mitogen-induced immunoglobulin synthesis. Similarly, suppressor function was induced in unfractionated CD4 T cell populations after incubation with anti-Leu-8 antibody under cross-linking conditions. This induction of suppressor function by anti-Leu-8 antibody was not due to expansion of the CD4, Leu-8+ T cell population because CD4 T cells did not proliferate in response to anti-Leu-8 antibody. However, CD4, Leu-8+ T cell-mediated suppression was radiosensitive. Finally, CD4, Leu-8+ T cells do not inhibit immunoglobulin synthesis when T cell lymphokines were used in place of helper CD4 T cells (CD4, Leu-8- T cells), suggesting that CD4 T cell-mediated suppression occurs at the T cell level. We conclude that CD4 T cells can be induced to suppress immunoglobulin synthesis by modulation of the membrane antigen recognized by anti-Leu-8 antibody

In vitro regulation of immunoglobulin synthesis after human marrow transplantation. II. Deficient T and non-T lymphocyte function within 3-4 months of allogeneic, syngeneic, or autologous marrow grafting for hematologic malignancy

International Nuclear Information System (INIS)

Witherspoon, R.P.; Lum, L.G.; Storb, R.; Thomas, E.D.

1982-01-01

Immunoglobulin secretion was studied in 37 patients between 19 and 106 days after allogeneic HLA-identical (30 patients), allogeneic one HLA-haplotype-identical (three patients), syngeneic (three patients), or autologous (one patient) marrow grafting. E rosette-positive (T) and E rosette-negative (non-T) peripheral blood mononuclear cells were cocultured with pokeweed mitogen for 6 days. Polyvalent immunoglobulin secretion was determined by counting plaque forming cells in a reverse hemolytic plaque assay. The number of antibody secreting cells in cocultures of autologous T and non-T lymphocytes was low in 40 of 44 tests conducted on samples from the 37 patients. Mononuclear or non-T cells from 38 of 40 tests failed to produce antibody when cultured with normal helper T cells. T cells from 23 of 37 tests failed to help normal non-T cells secrete antibody. T lymphocytes from 23 of 41 tests suppressed antibody production greater than 80% by normal T and non-T cells. The suppressor cells were radiosensitive in 17 of the 25 tests. The abnormal function of lymphocyte subpopulations in patients during the first 3 mo after syngeneic, allogeneic or autologous marrow grafting was similar regardless of the type of graft or the presence of acute graft versus host disease

Stimulation of pancreatic beta-cell replication by incretins involves transcriptional induction of cyclin D1 via multiple signalling pathways

DEFF Research Database (Denmark)

Friedrichsen, Birgitte N; Neubauer, Nicole; Lee, Ying C

2006-01-01

pathways leading to mitosis by incretins and cytokines, respectively. The response to both GLP-1 and GIP was completely blocked by the protein kinase A (PKA) inhibitor, H89. In addition, the phosphoinositol 3-kinase (PI3K) inhibitor wortmannin and the mitogen-activated protein kinase kinase (MEK) inhibitor...... and we have previously demonstrated hGH-induced cyclin D2 expression in the insulinoma cell line, INS-1. GLP-1 time-dependently induced the cyclin D1 mRNA and protein levels in INS-1E, whereas the cyclin D2 levels were unaffected. However, minor effect of GLP-1 stimulation was observed on the cyclin D3 m......RNA levels. Transient transfection of a cyclin D1 promoter-luciferase reporter construct into islet monolayer cells or INS-1 cells revealed approximately a 2-3 fold increase of transcriptional activity in response to GLP-1 and GIP, and a 4-7 fold increase in response to forskolin. However, treatment...

Pancreatic cancer stimulates pancreatic stellate cell proliferation and TIMP-1 production through the MAP kinase pathway

International Nuclear Information System (INIS)

Yoshida, Seiya; Yokota, Tokuyasu; Ujiki, Michael; Ding Xianzhong; Pelham, Carolyn; Adrian, Thomas E.; Talamonti, Mark S.; Bell, Richard H.; Denham, Woody

2004-01-01

Pancreatic adenocarcinoma is characterized by an intense desmoplastic reaction that surrounds the tumor. Pancreatic stellate cells (PSCs) are thought to be responsible for production of this extracellular matrix. When activated, PSCs have a myofibroblast phenotype and produce not only components of the extracellular matrix including collagen, fibronectin, and laminin, but also matrix metalloproteinases and tissue inhibitors of metalloproteinases (TIMPs). Since PSCs are found in the stroma surrounding human pancreatic adenocarcinoma, we postulate that pancreatic cancer could impact PSC proliferation and TIMP-1 production. Rat PSCs were isolated and cultured. Isolated PSCs were exposed to PANC-1 conditioned medium (CM) and proliferation, activation of the mitogen-activated protein (MAP) kinase pathway, and TIMP-1 gene induction were determined. Exposure to PANC-1 CM increased PSC DNA synthesis, cell number, and TIMP-1 mRNA (real-time PCR) as well as activating the extracellular-regulated kinase (ERK) 1/2. Inhibition of ERK 1/2 phosphorylation (U0126) prevented the increases in growth and TIMP-1 expression. PANC-1 CM stimulates PSC proliferation and TIMP-1 through the MAP kinase (ERK 1/2) pathway

Receptor trafficking via the perinuclear recycling compartment accompanied by cell division is necessary for permanent neurotensin cell sensitization and leads to chronic mitogen-activated protein kinase activation.

Science.gov (United States)

Toy-Miou-Leong, Mireille; Cortes, Catherine Llorens; Beaudet, Alain; Rostène, William; Forgez, Patricia

2004-03-26

Most G protein-coupled receptors are internalized after interaction with their respective ligand, a process that subsequently contributes to cell desensitization, receptor endocytosis, trafficking, and finally cell resensitization. Although cellular mechanisms leading to cell desensitization have been widely studied, those responsible for cell resensitization are still poorly understood. We examined here the traffic of the high affinity neurotensin receptor (NT1 receptor) following prolonged exposure to high agonist concentration. Fluorescence and confocal microscopy of Chinese hamster ovary, human neuroblastoma (CHP 212), and murine neuroblastoma (N1E-115) cells expressing green fluorescent protein-tagged NT1 receptor revealed that under prolonged treatment with saturating concentrations of neurotensin (NT) agonist, NT1 receptor and NT transiently accumulated in the perinuclear recycling compartment (PNRC). During this cellular event, cell surface receptors remained markedly depleted as detected by both confocal microscopy and (125)I-NT binding assays. In dividing cells, we observed that following prolonged NT agonist stimulation, NT1 receptors were removed from the PNRC, accumulated in dispersed vesicles inside the cytoplasm, and subsequently reappeared at the cell surface. This NT binding recovery allowed for constant cell sensitization and led to a chronic activation of mitogen-activated protein kinases p42 and p44. Under these conditions, the constant activation of NT1 receptor generates an oncogenic regulation. These observations support the potent role for neuropeptides, such as NT, in cancer progression.

Mitogenic activity of a water-soluble adjuvant (Bu-WSA) obtained from Bacterionema matruchotii. IV. Synergistic effects of Bu-WSA on Concanavalin A-induced proliferative response of human peripheral blood lymphocytes.

Science.gov (United States)

Nitta, T; Okumura, S; Tsushi, M; Nakano, M

1982-01-01

Butanol-extracted water-soluble adjuvant (Bu-WSA) obtained from Bacterionema matruchotii was cultured with peripheral blood mononuclear cells (PBM) in the presence of sub- and/or supra-optimal mitogenic concentrations of concanavalin A (Con A). The addition of Bu-WSA resulted in increased tritiated thymidine incorporation above that produced by Con A alone. Bu-WSA by itself is not mitogenic for PBM and in fact produced a decrease in thymidine uptake compared to the control. We investigated the response of subpopulation(s) of PBM to Bu-WSA, Con A and a mixture of Bu-WSA and Con A. Separation of PBM into purified T cells, B cells and macrophages showed that cell-cell cooperation of T cells with B cells or macrophages is necessary for the observed synergistic effect of Bu-WSA with Con A. A marked increase in thymidine incorporation by the mixture of T and B cell populations occurred, while only a small amount of thymidine was incorporated when the B cell population was absent. Mitomycin treatment revealed that the response could be ascribed to the T-cell response with a B-cell helper effect. Moreover, Con A and Bu-WSA appeared to act on the same T cell population. This model may provide unique information about the activation of human peripheral blood T cells compared with the activation of these cells by other mitogens.

Brain Stimulation Therapies

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... Magnetic Seizure Therapy Deep Brain Stimulation Additional Resources Brain Stimulation Therapies Overview Brain stimulation therapies can play ... for a shorter recovery time than ECT Deep Brain Stimulation Deep brain stimulation (DBS) was first developed ...

Computationally Developed Sham Stimulation Protocol for Multichannel Desynchronizing Stimulation

Directory of Open Access Journals (Sweden)

Magteld Zeitler

2018-05-01

Full Text Available A characteristic pattern of abnormal brain activity is abnormally strong neuronal synchronization, as found in several brain disorders, such as tinnitus, Parkinson's disease, and epilepsy. As observed in several diseases, different therapeutic interventions may induce a placebo effect that may be strong and hinder reliable clinical evaluations. Hence, to distinguish between specific, neuromodulation-induced effects and unspecific, placebo effects, it is important to mimic the therapeutic procedure as precisely as possibly, thereby providing controls that actually lack specific effects. Coordinated Reset (CR stimulation has been developed to specifically counteract abnormally strong synchronization by desynchronization. CR is a spatio-temporally patterned multichannel stimulation which reduces the extent of coincident neuronal activity and aims at an anti-kindling, i.e., an unlearning of both synaptic connectivity and neuronal synchrony. Apart from acute desynchronizing effects, CR may cause sustained, long-lasting desynchronizing effects, as already demonstrated in pre-clinical and clinical proof of concept studies. In this computational study, we set out to computationally develop a sham stimulation protocol for multichannel desynchronizing stimulation. To this end, we compare acute effects and long-lasting effects of six different spatio-temporally patterned stimulation protocols, including three variants of CR, using a no-stimulation condition as additional control. This is to provide an inventory of different stimulation algorithms with similar fundamental stimulation parameters (e.g., mean stimulation rates but qualitatively different acute and/or long-lasting effects. Stimulation protocols sharing basic parameters, but inducing nevertheless completely different or even no acute effects and/or after-effects, might serve as controls to validate the specific effects of particular desynchronizing protocols such as CR. In particular, based on

Assessment of clusters of transcription factor binding sites in relationship to human promoter, CpG islands and gene expression

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Sakaki Yoshiyuki

2004-02-01

Full Text Available Abstract Background Gene expression is regulated mainly by transcription factors (TFs that interact with regulatory cis-elements on DNA sequences. To identify functional regulatory elements, computer searching can predict TF binding sites (TFBS using position weight matrices (PWMs that represent positional base frequencies of collected experimentally determined TFBS. A disadvantage of this approach is the large output of results for genomic DNA. One strategy to identify genuine TFBS is to utilize local concentrations of predicted TFBS. It is unclear whether there is a general tendency for TFBS to cluster at promoter regions, although this is the case for certain TFBS. Also unclear is the identification of TFs that have TFBS concentrated in promoters and to what level this occurs. This study hopes to answer some of these questions. Results We developed the cluster score measure to evaluate the correlation between predicted TFBS clusters and promoter sequences for each PWM. Non-promoter sequences were used as a control. Using the cluster score, we identified a PWM group called PWM-PCP, in which TFBS clusters positively correlate with promoters, and another PWM group called PWM-NCP, in which TFBS clusters negatively correlate with promoters. The PWM-PCP group comprises 47% of the 199 vertebrate PWMs, while the PWM-NCP group occupied 11 percent. After reducing the effect of CpG islands (CGI against the clusters using partial correlation coefficients among three properties (promoter, CGI and predicted TFBS cluster, we identified two PWM groups including those strongly correlated with CGI and those not correlated with CGI. Conclusion Not all PWMs predict TFBS correlated with human promoter sequences. Two main PWM groups were identified: (1 those that show TFBS clustered in promoters associated with CGI, and (2 those that show TFBS clustered in promoters independent of CGI. Assessment of PWM matches will allow more positive interpretation of TFBS in

Fisetin inhibits IL-31 production in stimulated human mast cells: Possibilities of fisetin being exploited to treat histamine-independent pruritus.

Science.gov (United States)

Che, Denis Nchang; Cho, Byoung Ok; Shin, Jae Young; Kang, Hyun Ju; Kim, Young-Soo; Jang, Seon Il

2018-05-15

Interleukin-31 (IL-31) is a recently discovered cytokine that is tightly linked to the pathogenesis of pruritus seen in atopic dermatitis. Flavonoids, like fisetin, are naturally occurring molecules with antioxidant, cytoprotective, and anti-inflammatory actions. the present study sought to investigate whether fisetin modulates IL-31 and histamine release in human mast cells (HMC-1). HMC-1 cells were pretreated with fisetin at various doses and stimulated with phorbol-12-myristate 13-acetate and calcium ionophore A23187 (PI) for different time intervals. We evaluated IL-31 production and histamine release and signaling mechanism of the action of fisetin on IL-31 production. We also investigated the effects of fisetin on scratching behaviors in mice. Fisetin decreased PI-stimulated mRNA expression and production of IL-31 in HMC-1 cells. Fisetin inhibited PI-induced phosphorylation of mitogen-activated protein kinases that further suppressed nuclear factor (NF-κB) activation and translocation to the nucleus through the inhibition of IκB-α phosphorylation. Fisetin also prevented mast cell release of histamine in HMC-1 cells. Mice in-vivo studies show that fisetin reduced scratching behaviors in mice. These pharmacological actions of fisetin provide new suggestions that fisetin can be of potential use for the treatment of pruritus that cannot be treated with histamine receptor blockers alone. Copyright © 2018 Elsevier Inc. All rights reserved.

ER-α36 mediates estrogen-stimulated MAPK/ERK activation and regulates migration, invasion, proliferation in cervical cancer cells

International Nuclear Information System (INIS)

Sun, Qing; Liang, Ying; Zhang, Tianli; Wang, Kun; Yang, Xingsheng

2017-01-01

Objective: Estrogen receptor alpha 36 (ER-α36), a truncated variant of ER-α, is different from other nuclear receptors of the ER-α family. Previous findings indicate that ER-α36 might be involved in cell growth, proliferation, and differentiation in carcinomas and primarily mediates non-genomic estrogen signaling. However, studies on ER-α36 and cervical cancer are rare. This study aimed to detect the expression of ER-α36 in cervical cancer; the role of ER-α36 in 17-β-estradiol (E2)-induced invasion, migration and proliferation of cervical cancer; and their probable molecular mechanisms. Methods: Immunohistochemistry and immunofluorescence were used to determine the location of ER-α36 in cervical cancer tissues and cervical cell lines. CaSki and HeLa cell lines were transfected with lentiviruses to establish stable cell lines with knockdown and overexpression of ER-α36. Wound healing assay, transwell invasion assay, and EdU incorporation proliferation assay were performed to evaluate the migration, invasion, and proliferation ability. The phosphorylation levels of mitogen-activated protein kinases/extracellular signal-regulated kinase (MAPK/ERK) signaling molecules were examined with western blot analysis. Results: ER-α36 expression was detected in both cervical cell lines and cervical cancer tissues. Downregulation of ER-α36 significantly inhibited cell invasion, migration, and proliferation. Moreover, upregulation of ER-α36 increased the invasion, migration, and proliferation ability of CaSki and HeLa cell lines. ER-α36 mediates estrogen-stimulated MAPK/ERK activation. Conclusion: ER-α36 is localized on the plasma membrane and cytoplasm in both cervical cancer tissues and cell lines. ER-α36 mediates estrogen-stimulated MAPK/ERK activation and regulates migration, invasion, proliferation in cervical cancer cells. - Highlights: • ER-α36 is expressed on both cervical cell lines and cervical cancer tissues. • ER-α36 mediates estrogen-stimulated

Effects of phorbol ester on mitogen-activated protein kinase kinase activity in wild-type and phorbol ester-resistant EL4 thymoma cells.

Science.gov (United States)

Gause, K C; Homma, M K; Licciardi, K A; Seger, R; Ahn, N G; Peterson, M J; Krebs, E G; Meier, K E

1993-08-05

Phorbol ester-sensitive and -resistant EL4 thymoma cell lines differ in their ability to activate mitogen-activated protein kinase (MAPK) in response to phorbol ester. Treatment of wild-type EL4 cells with phorbol ester results in the rapid activations of MAPK and pp90rsk kinase, a substrate for MAPK, while neither kinase is activated in response to phorbol ester in variant EL4 cells. This study examines the activation of MAPK kinase (MAPKK), an activator of MAPK, in wild-type and variant EL4 cells. Phosphorylation of a 40-kDa substrate, identified as MAPK, was observed following in vitro phosphorylation reactions using cytosolic extracts or Mono Q column fractions prepared from phorbol ester-treated wild-type EL4 cells. MAPKK activity coeluted with a portion of the inactive MAPK upon Mono Q anion-exchange chromatography, permitting detection of the MAPKK activity in fractions containing both kinases. This MAPKK activity was present in phorbol ester-treated wild-type cells, but not in phorbol ester-treated variant cells or in untreated wild-type or variant cells. The MAPKK from wild-type cells was able to activate MAPK prepared from either wild-type or variant cells. MAPKK activity could be stimulated in both wildtype and variant EL4 cells in response to treatment of cells with okadaic acid. These results indicate that the failure of variant EL4 cells to activate MAP kinase in response to phorbol ester is due to a failure to activate MAPKK. Therefore, the step that confers phorbol ester resistance to variant EL4 cells lies between the activation of protein kinase C and the activation of MAPKK.

Towards a Switched-Capacitor Based Stimulator for Efficient Deep-Brain Stimulation

Science.gov (United States)

Vidal, Jose; Ghovanloo, Maysam

2013-01-01

We have developed a novel 4-channel prototype stimulation circuit for implantable neurological stimulators (INS). This Switched-Capacitor based Stimulator (SCS) aims to utilize charge storage and charge injection techniques to take advantage of both the efficiency of conventional voltage-controlled stimulators (VCS) and the safety and controllability of current-controlled stimulators (CCS). The discrete SCS prototype offers fine control over stimulation parameters such as voltage, current, pulse width, frequency, and active electrode channel via a LabVIEW graphical user interface (GUI) when connected to a PC through USB. Furthermore, the prototype utilizes a floating current sensor to provide charge-balanced biphasic stimulation and ensure safety. The stimulator was analyzed using an electrode-electrolyte interface (EEI) model as well as with a pair of pacing electrodes in saline. The primary motivation of this research is to test the feasibility and functionality of a safe, effective, and power-efficient switched-capacitor based stimulator for use in Deep Brain Stimulation. PMID:21095987

Ultrasound stimulation on bone healing. The optimization of stimulation time

International Nuclear Information System (INIS)

Rosim, R.C.; Paulin, J.B.P.; Goncalves, R.P.

1990-01-01

Previous works in ultrasonic simulation of bone healing dealt with parameters optimization. Albertin (1983) studied the stimulation time and found forty minutes as ideal. However, this stimulation time was the largest one employed and remained some doubt about the most appropriated value. 30, 40, 50 and 60 minutes of stimulation time were selected, while others parameters were held constant with: pulse width in 200 μs, repetition rate in 1000 pulses per second and amplitude in 30 V. Partial incomplete transverse osteotomies were done in the middle third of radio in the right forearm of rabbits. Twenty four animals divided in four subgroups, with 6 animals each were stimulated. The daily stimulation time for each subgroup was 30, 40, 50 and minutes respectively, during 15 consecutive days. The stimulation procedure started 24 hours after surgery. After the stimulation period, radiological, histological and morphometric evaluations were done and greater bone healing was found for the 50 minutes stimulation subgroup, in them new bone was also prominent. (author)

The transcriptional co-repressor myeloid translocation gene 16 inhibits glycolysis and stimulates mitochondrial respiration.

Directory of Open Access Journals (Sweden)

Parveen Kumar

Full Text Available The myeloid translocation gene 16 product MTG16 is found in multiple transcription factor-containing complexes as a regulator of gene expression implicated in development and tumorigenesis. A stable Tet-On system for doxycycline-dependent expression of MTG16 was established in B-lymphoblastoid Raji cells to unravel its molecular functions in transformed cells. A noticeable finding was that expression of certain genes involved in tumor cell metabolism including 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 and 4 (PFKFB3 and PFKFB4, and pyruvate dehydrogenase kinase isoenzyme 1 (PDK1 was rapidly diminished when MTG16 was expressed. Furthermore, hypoxia-stimulated production of PFKFB3, PFKFB4 and PDK1 was inhibited by MTG16 expression. The genes in question encode key regulators of glycolysis and its coupling to mitochondrial metabolism and are commonly found to be overexpressed in transformed cells. The MTG16 Nervy Homology Region 2 (NHR2 oligomerization domain and the NHR3 protein-protein interaction domain were required intact for inhibition of PFKFB3, PFKFB4 and PDK1 expression to occur. Expression of MTG16 reduced glycolytic metabolism while mitochondrial respiration and formation of reactive oxygen species increased. The metabolic changes were paralleled by increased phosphorylation of mitogen-activated protein kinases, reduced levels of amino acids and inhibition of proliferation with a decreased fraction of cells in S-phase. Overall, our findings show that MTG16 can serve as a brake on glycolysis, a stimulator of mitochondrial respiration and an inhibitor of cell proliferation. Hence, elevation of MTG16 might have anti-tumor effect.

Mitogenic Activity of a Water-Soluble Adjuvant (Bu-WSA) Obtained from Bacterionema matruchotii: IV. Synergistic Effects of Bu-WSA on Concanavalin A-Induced Proliferative Response of Human Peripheral Blood Lymphocytes.

Science.gov (United States)

Nitta, Toshimasa; Okumura, Seiichi; Tsushi, Masao; Nakano, Masayasu

1982-07-01

Butanol-extracted water-soluble adjuvant (Bu-WSA) obtained from Bacterionema matruchotii was cultured with peripheral blood mononuclear cells (PBM) in the presence of sub- and/or supra-optimal mitogenic concentrations of concanavalin A (Con A). The addition of Bu-WSA resulted in increased tritiated thymidine incorporation above that produced by Con A alone. Bu-WSA by itself is not mitogenic for PBM and in fact produced a decrease in thymidine uptake compared to the control. We investigated the response of subpopulation(s) of PBM to Bu-WSA, Con A and a mixture of Bu-WSA and Con A. Separation of PBM into purified T cells, B cells and macrophages showed that cell-cell cooperation of T cells with B cells or macrophages is necessary for the observed synergistic effect of Bu-WSA with Con A. A marked increase in thymidine incorporation by the mixture of T and B cell populations occurred, while only a small amount of thymidine was incorporated when the B cell population was absent. Mitomycin treatment revealed that the response could be ascribed to the T-cell response with a B-cell helper effect. Moreover, Con A and Bu-WSA appeared to act on the same T cell population. This model may provide unique information about the activation of human peripheral blood T cells compared with the activation of these cells by other mitogens. © owned by Center for Academic Publications Japan (Publisher).

UVB-Stimulated TNFα Release from Human Melanocyte and Melanoma Cells Is Mediated by p38 MAPK

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Visalini Muthusamy

2013-08-01

Full Text Available Ultraviolet (UV radiation activates cell signaling pathways in melanocytes. As a result of altered signaling pathways and UV-induced cellular damage, melanocytes can undergo oncogenesis and develop into melanomas. In this study, we investigated the effect of UV-radiation on p38 MAPK (mitogen-activated protein kinase, JNK and NFκB pathways to determine which plays a major role in stimulating TNFα secretion in human HEM (melanocytes and MM96L (melanoma cells. MM96L cells exhibited 3.5-fold higher p38 activity than HEM cells at 5 min following UVA + B radiation and 1.6-fold higher JNK activity at 15–30 min following UVB+A radiation, while NFκB was minimally activated in both cells. Irradiated HEM cells had the greatest fold of TNFα secretion (UVB: 109-fold, UVA + B: 103-fold & UVB+A: 130-fold when co-exposed to IL1α. The p38 inhibitor, SB202190, inhibited TNFα release by 93% from UVB-irradiated HEM cells. In the UVB-irradiated MM96L cells, both SB202190 and sulfasalazine (NFκB inhibitor inhibited TNFα release by 52%. Although, anisomycin was a p38 MAPK activator, it inhibited TNFα release in UV-irradiated cells. This suggests that UV-mediated TNFα release may occur via different p38 pathway intermediates compared to those stimulated by anisomycin. As such, further studies into the functional role p38 MAPK plays in regulating TNFα release in UV-irradiated melanocyte-derived cells are warranted.

Multiplicity of carbohydrate-binding sites in β-prism fold lectins ...

Indian Academy of Sciences (India)

PRAKASH KUMAR

cancer metastasis, embryogenesis, tissue development and mitogenic stimulation ... within the sequence exhibit reasonable correlation. The distribution of the ..... II fold lectins with known structure in complex with sugar. Sugars are shown in ...

Terbinafine: effects on platelet-derived growth factor-stimulated smooth muscle cells in vitro and myointimal proliferation in vivo

International Nuclear Information System (INIS)

McCarthy, L.; Van Halen, R.G.; St Denny, I.H.; Glinka, K.G.; Handley, D.A.; Stuetz, A.; Nemecek, G.M.

1987-01-01

Terbinafine (T; (E)-N-(6,6-dimethyl-2-hepten-4-ynyl)-N-methyl-1-naphthalenemethanamine), an antimycotic agent with antimitogenic activity in fibroblasts, was examined for its effects on platelet-derived growth factor (PDGF)-stimulated aortic smooth muscle cell DNA synthesis in vitro and myointimal proliferation in vivo. Exposure of smooth muscle cells to 1-25 μM T resulted in a concentration-dependent inhibition of PDGF-induced mitogenesis as determined by [ 3 H]thymidine incorporation or cell number. The IC 50 for T was approximately 5 μM. The inhibitory effect of terbinafine persisted in the presence of 0.4-8.0 μg/ml cholesterol or 130 μg/ml mevalonate. Administration of T to rats for 2 d before and 14 d after balloon catheter carotid injury resulted in a 40% decrease in lesion area. These observations indicate that T is both a potent in vitro antagonist of the smooth muscle cell mitogenic response to PDGF and an effective, well-tolerated, orally active inhibitor of myointimal proliferation in vivo

Terbinafine: effects on platelet-derived growth factor-stimulated smooth muscle cells in vitro and myointimal proliferation in vivo

Energy Technology Data Exchange (ETDEWEB)

McCarthy, L.; Van Halen, R.G.; St. Denny, I.H.; Glinka, K.G.; Handley, D.A.; Stuetz, A.; Nemecek, G.M.

1987-05-01

Terbinafine (T; (E)-N-(6,6-dimethyl-2-hepten-4-ynyl)-N-methyl-1-naphthalenemethanamine), an antimycotic agent with antimitogenic activity in fibroblasts, was examined for its effects on platelet-derived growth factor (PDGF)-stimulated aortic smooth muscle cell DNA synthesis in vitro and myointimal proliferation in vivo. Exposure of smooth muscle cells to 1-25 ..mu..M T resulted in a concentration-dependent inhibition of PDGF-induced mitogenesis as determined by (/sup 3/H)thymidine incorporation or cell number. The IC/sub 50/ for T was approximately 5 ..mu..M. The inhibitory effect of terbinafine persisted in the presence of 0.4-8.0 ..mu..g/ml cholesterol or 130 ..mu..g/ml mevalonate. Administration of T to rats for 2 d before and 14 d after balloon catheter carotid injury resulted in a 40% decrease in lesion area. These observations indicate that T is both a potent in vitro antagonist of the smooth muscle cell mitogenic response to PDGF and an effective, well-tolerated, orally active inhibitor of myointimal proliferation in vivo.

Cytotoxicity and mitogenicity assays with real-time and label-free monitoring of human granulosa cells with an impedance-based signal processing technology intergrating micro-electronics and cell biology.

Science.gov (United States)

Oktem, Ozgur; Bildik, Gamze; Senbabaoglu, Filiz; Lack, Nathan A; Akin, Nazli; Yakar, Feridun; Urman, Defne; Guzel, Yilmaz; Balaban, Basak; Iwase, Akira; Urman, Bulent

2016-04-01

A recently developed technology (xCelligence) integrating micro-electronics and cell biology allows real-time, uninterrupted and quantitative analysis of cell proliferation, viability and cytotoxicity by measuring the electrical impedance of the cell population in the wells without using any labeling agent. In this study we investigated if this system is a suitable model to analyze the effects of mitogenic (FSH) and cytotoxic (chemotherapy) agents with different toxicity profiles on human granulosa cells in comparison to conventional methods of assessing cell viability, DNA damage, apoptosis and steroidogenesis. The system generated the real-time growth curves of the cells, and determined their doubling times, mean cell indices and generated dose-response curves after exposure to cytotoxic and mitogenic stimuli. It accurately predicted the gonadotoxicity of the drugs and distinguished less toxic agents (5-FU and paclitaxel) from more toxic ones (cisplatin and cyclophosphamide). This platform can be a useful tool for specific end-point assays in reproductive toxicology. Copyright © 2015 Elsevier Inc. All rights reserved.

Catalase overexpression prevents nuclear factor erythroid 2-related factor 2 stimulation of renal angiotensinogen gene expression, hypertension, and kidney injury in diabetic mice.

Science.gov (United States)

Abdo, Shaaban; Shi, Yixuan; Otoukesh, Abouzar; Ghosh, Anindya; Lo, Chao-Sheng; Chenier, Isabelle; Filep, Janos G; Ingelfinger, Julie R; Zhang, Shao Ling; Chan, John S D

2014-10-01

This study investigated the impact of catalase (Cat) overexpression in renal proximal tubule cells (RPTCs) on nuclear factor erythroid 2-related factor 2 (Nrf2) stimulation of angiotensinogen (Agt) gene expression and the development of hypertension and renal injury in diabetic Akita transgenic mice. Additionally, adult male mice were treated with the Nrf2 activator oltipraz with or without the inhibitor trigonelline. Rat RPTCs, stably transfected with plasmid containing either rat Agt or Nrf2 gene promoter, were also studied. Cat overexpression normalized systolic BP, attenuated renal injury, and inhibited RPTC Nrf2, Agt, and heme oxygenase-1 (HO-1) gene expression in Akita Cat transgenic mice compared with Akita mice. In vitro, high glucose level, hydrogen peroxide, and oltipraz stimulated Nrf2 and Agt gene expression; these changes were blocked by trigonelline, small interfering RNAs of Nrf2, antioxidants, or pharmacological inhibitors of nuclear factor-κB and p38 mitogen-activated protein kinase. The deletion of Nrf2-responsive elements in the rat Agt gene promoter abolished the stimulatory effect of oltipraz. Oltipraz administration also augmented Agt, HO-1, and Nrf2 gene expression in mouse RPTCs and was reversed by trigonelline. These data identify a novel mechanism, Nrf2-mediated stimulation of intrarenal Agt gene expression and activation of the renin-angiotensin system, by which hyperglycemia induces hypertension and renal injury in diabetic mice. © 2014 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

Stimulating at the right time: phase-specific deep brain stimulation.

Science.gov (United States)

Cagnan, Hayriye; Pedrosa, David; Little, Simon; Pogosyan, Alek; Cheeran, Binith; Aziz, Tipu; Green, Alexander; Fitzgerald, James; Foltynie, Thomas; Limousin, Patricia; Zrinzo, Ludvic; Hariz, Marwan; Friston, Karl J; Denison, Timothy; Brown, Peter

2017-01-01

SEE MOLL AND ENGEL DOI101093/AWW308 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE: Brain regions dynamically engage and disengage with one another to execute everyday actions from movement to decision making. Pathologies such as Parkinson's disease and tremor emerge when brain regions controlling movement cannot readily decouple, compromising motor function. Here, we propose a novel stimulation strategy that selectively regulates neural synchrony through phase-specific stimulation. We demonstrate for the first time the therapeutic potential of such a stimulation strategy for the treatment of patients with pathological tremor. Symptom suppression is achieved by delivering stimulation to the ventrolateral thalamus, timed according to the patient's tremor rhythm. Sustained locking of deep brain stimulation to a particular phase of tremor afforded clinically significant tremor relief (up to 87% tremor suppression) in selected patients with essential tremor despite delivering less than half the energy of conventional high frequency stimulation. Phase-specific stimulation efficacy depended on the resonant characteristics of the underlying tremor network. Selective regulation of neural synchrony through phase-locked stimulation has the potential to both increase the efficiency of therapy and to minimize stimulation-induced side effects. © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain.

Neural cell adhesion molecule-stimulated neurite outgrowth depends on activation of protein kinase C and the Ras-mitogen-activated protein kinase pathway

DEFF Research Database (Denmark)

Kolkova, K; Novitskaya, V; Pedersen, N

2000-01-01

, inhibitors of the nonreceptor tyrosine kinase p59(fyn), PLC, PKC and MEK and an activator of PKC, phorbol-12-myristate-13-acetate (PMA). MEK2 transfection rescued cells treated with all inhibitors. The same was found for PMA treatment, except when cells concomitantly were treated with the MEK inhibitor....... Arachidonic acid rescued cells treated with antibodies to the FGF receptor or the PLC inhibitor, but not cells in which the activity of PKC, p59(fyn), FAK, Ras, or MEK was inhibited. Interaction of NCAM with a synthetic NCAM peptide ligand, known to induce neurite outgrowth, was shown to stimulate...... phosphorylation of the MAP kinases extracellular signal-regulated kinases ERK1 and ERK2. The MAP kinase activation was sustained, because ERK1 and ERK2 were phosphorylated in PC12-E2 cells and primary hippocampal neurons even after 24 hr of cultivation on NCAM-expressing fibroblasts. Based on these results, we...

[Transcranial magnetic stimulation and motor cortex stimulation in neuropathic pain].

Science.gov (United States)

Mylius, V; Ayache, S S; Teepker, M; Kappus, C; Kolodziej, M; Rosenow, F; Nimsky, C; Oertel, W H; Lefaucheur, J P

2012-12-01

Non-invasive and invasive cortical stimulation allows the modulation of therapy-refractory neuropathic pain. High-frequency repetitive transcranial magnetic stimulation (rTMS) of the contralateral motor cortex yields therapeutic effects at short-term and predicts the benefits of epidural motor cortex stimulation (MCS). The present article summarizes the findings on application, mechanisms and therapeutic effects of cortical stimulation in neuropathic pain.

Stimulating the Comfort of Textile Electrodes in Wearable Neuromuscular Electrical Stimulation

Science.gov (United States)

Zhou, Hui; Lu, Yi; Chen, Wanzhen; Wu, Zhen; Zou, Haiqing; Krundel, Ludovic; Li, Guanglin

2015-01-01

Textile electrodes are becoming an attractive means in the facilitation of surface electrical stimulation. However, the stimulation comfort of textile electrodes and the mechanism behind stimulation discomfort is still unknown. In this study, a textile stimulation electrode was developed using conductive fabrics and then its impedance spectroscopy, stimulation thresholds, and stimulation comfort were quantitatively assessed and compared with those of a wet textile electrode and a hydrogel electrode on healthy subjects. The equivalent circuit models and the finite element models of different types of electrode were built based on the measured impedance data of the electrodes to reveal the possible mechanism of electrical stimulation pain. Our results showed that the wet textile electrode could achieve similar stimulation performance as the hydrogel electrode in motor threshold and stimulation comfort. However, the dry textile electrode was found to have very low pain threshold and induced obvious cutaneous painful sensations during stimulation, in comparison to the wet and hydrogel electrodes. Indeed, the finite element modeling results showed that the activation function along the z direction at the depth of dermis epidermis junction of the dry textile electrode was significantly larger than that of the wet and hydrogel electrodes, thus resulting in stronger activation of pain sensing fibers. Future work will be done to make textile electrodes have similar stimulation performance and comfort as hydrogel electrodes. PMID:26193273

Stimulating the Comfort of Textile Electrodes in Wearable Neuromuscular Electrical Stimulation

Directory of Open Access Journals (Sweden)

Hui Zhou

2015-07-01

Full Text Available Textile electrodes are becoming an attractive means in the facilitation of surface electrical stimulation. However, the stimulation comfort of textile electrodes and the mechanism behind stimulation discomfort is still unknown. In this study, a textile stimulation electrode was developed using conductive fabrics and then its impedance spectroscopy, stimulation thresholds, and stimulation comfort were quantitatively assessed and compared with those of a wet textile electrode and a hydrogel electrode on healthy subjects. The equivalent circuit models and the finite element models of different types of electrode were built based on the measured impedance data of the electrodes to reveal the possible mechanism of electrical stimulation pain. Our results showed that the wet textile electrode could achieve similar stimulation performance as the hydrogel electrode in motor threshold and stimulation comfort. However, the dry textile electrode was found to have very low pain threshold and induced obvious cutaneous painful sensations during stimulation, in comparison to the wet and hydrogel electrodes. Indeed, the finite element modeling results showed that the activation function along the z direction at the depth of dermis epidermis junction of the dry textile electrode was significantly larger than that of the wet and hydrogel electrodes, thus resulting in stronger activation of pain sensing fibers. Future work will be done to make textile electrodes have similar stimulation performance and comfort as hydrogel electrodes.

Mitogen-activated protein kinase phosphatase (MKP)-1 as a neuroprotective agent: promotion of the morphological development of midbrain dopaminergic neurons.

Science.gov (United States)

Collins, Louise M; O'Keeffe, Gerard W; Long-Smith, Caitriona M; Wyatt, Sean L; Sullivan, Aideen M; Toulouse, André; Nolan, Yvonne M

2013-06-01

A greater understanding of the mechanisms that promote the survival and growth of dopaminergic neurons is essential for the advancement of cell replacement therapies for Parkinson's disease (PD). Evidence supports a role for the mitogen-activated protein kinase p38 in the demise of dopaminergic neurons, while mitogen-activated protein kinase phosphatase-1 (MKP-1), which negatively regulates p38 activity, has not yet been investigated in this context. Here, we show that MKP-1 is expressed in dopaminergic neurons cultured from E14 rat ventral mesencephalon (VM). When dopaminergic neurons were transfected to overexpress MKP-1, they displayed a more complex morphology than their control counterparts in vitro. Specifically, MKP-1-transfection induced significant increases in neurite length and branching with a maximum increase observed in primary branches. We demonstrate that inhibition of dopaminergic neurite growth induced by treatment of rat VM neurons with the dopaminergic neurotoxin 6-hydroxydopamine (6-OHDA) in vitro is mediated by p38 and is concomitant with a significant and selective decrease in MKP-1 expression in these neurons. We further show that overexpression of MKP-1 in dopaminergic neurons contributes to neuroprotection against the effects of 6-OHDA. Collectively, we report that MKP-1 can promote the growth and elaboration of dopaminergic neuronal processes and can help protect them from the neurotoxic effects of 6-OHDA. Thus, we propose that strategies aimed at augmenting MKP-1 expression or activity may be beneficial in protecting dopaminergic neurons and may provide potential therapeutic approaches for PD.

Investigation of thermodynamic parameters in the thermal decomposition of plastic waste-waste lube oil compounds.

Science.gov (United States)

Kim, Yong Sang; Kim, Young Seok; Kim, Sung Hyun

2010-07-01

Thermal decomposition properties of plastic waste-waste lube oil compounds were investigated under nonisothermal conditions. Polyethylene (PE), polypropylene (PP), polystyrene (PS), and polyethylene terephthalate (PET) were selected as representative household plastic wastes. A plastic waste mixture (PWM) and waste lube oil (WLO) were mixed with mixing ratios of 33, 50, and 67 (w/w) % on a PWM weight basis, and thermogravimetric (TG) experiments were performed from 25 to 600 degrees C. The Flynn-Wall method and the Ozawa-Flynn-Wall method were used for analyses of thermodynamic parameters. In this study, activation energies of PWM/WLO compounds ranged from 73.4 to 229.6 kJ/mol between 0.2 and 0.8 of normalized mass conversions, and the 50% PWM/WLO compound had lower activation energies and enthalpies among the PWM/WLO samples at each mass conversion. At the point of maximum differential mass conversion, the analyzed activation energies, enthalpies, entropies, and Gibbs free energies indicated that mixing PWM and WLO has advantages in reducing energy to decrease the degree of disorder. However, no difference in overall energy that would require overcoming both thermal decomposition reactions and degree of disorder was observed among PWM/WLO compounds under these experimental conditions.

Context Specificity of Stress-activated Mitogen-activated Protein (MAP) Kinase Signaling: The Story as Told by Caenorhabditis elegans*

Science.gov (United States)

Andrusiak, Matthew G.; Jin, Yishi

2016-01-01

Stress-associated p38 and JNK mitogen-activated protein (MAP) kinase signaling cascades trigger specific cellular responses and are involved in multiple disease states. At the root of MAP kinase signaling complexity is the differential use of common components on a context-specific basis. The roundworm Caenorhabditis elegans was developed as a system to study genes required for development and nervous system function. The powerful genetics of C. elegans in combination with molecular and cellular dissections has led to a greater understanding of how p38 and JNK signaling affects many biological processes under normal and stress conditions. This review focuses on the studies revealing context specificity of different stress-activated MAPK components in C. elegans. PMID:26907690

TNF-α stimulates System A amino acid transport in primary human trophoblast cells mediated by p38 MAPK signaling.

Science.gov (United States)

Aye, Irving L M H; Jansson, Thomas; Powell, Theresa L

2015-10-01

Maternal obesity and gestational diabetes mellitus (GDM) increase the risk of delivering infants that are large for gestational age with greater adiposity, who are prone to the development of metabolic disease in childhood and beyond. These maternal conditions are also associated with increased levels of the proinflammatory cytokine TNF-α in maternal tissues and the placenta. Recent evidence suggests that changes in placental amino acid transport contribute to altered fetal growth. TNF-α was previously shown to stimulate System A amino acid transport in primary human trophoblasts (PHTs), however the molecular mechanisms remain unknown. In this study, we tested the hypothesis that TNF-α regulates amino acid uptake in cultured PHTs by a mitogen-activated protein kinase (MAPK)-dependent mechanism. Treatment of PHTs with TNF-α significantly increased System A amino acid transport, as well as Erk and p38 MAPK signaling. Pharmacological antagonism of p38, but not Erk MAPK activity, inhibited TNF-α stimulated System A activity. Silencing of p38 MAPK using siRNA transfections prevented TNF-α stimulated System A transport in PHTs. TNF-α significantly increased the protein expression of System A transporters SNAT1 and SNAT2, but did not affect their mRNA expression. The effects of TNF-α on SNAT1 and SNAT2 protein expression were reversed by p38 MAPK siRNA silencing. In conclusion, TNF-α regulates System A activity through increased SNAT1 and SNAT2 transporter protein expression in PHTs. These findings suggest that p38 MAPK may represent a critical mechanistic link between elevated proinflammatory cytokines and increased placental amino acid transport in obese and GDM pregnancies associated with fetal overgrowth. © 2015 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

Effect of the semen extract of Cuscuta chinensis on inflammatory responses in LPS-stimulated BV-2 microglia.

Science.gov (United States)

Kang, Seok Yong; Jung, Hyo Won; Lee, Mi-Young; Lee, Hye Won; Chae, Seong Wook; Park, Yong-Ki

2014-08-01

To investigate the anti-inflammatory activities of the semen extract of Cuscuta chinensis Lam. (Cuscutae Semen; CS) on the production of inflammatory mediators, nitric oxide (NO), prostaglandin 2 (PGE2), and proinflammatory cytokines in lipopolysaccharide (LPS)-stimulated BV-2 microglia. BV-2 cells were treated with CS extract for 30 min, and then stimulated with LPS or without for 24 h. The levels of NO, PGE2 and proinflammatory cytokines were measured by Griess assay and ELISA. The expression of inducible nitric oxide synthase (iNOS), and cyclooxygenase (COX)-2 mRNA and protein was determined by RT-PCR and Western blot, respectively. The phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2), Jun N-terminal kinase (JNK), and p38 mitogen-activated protein kinase (MAPK), and the nuclear expression of nuclear factor (NF)-κB p65 were investigated by Western blot analysis. CS extract significantly decreased the production of NO and PGE2 by suppressing the expression of iNOS and COX-2 in activated microglia. CS extract decreased the production of TNF-α, IL-1β, and IL-6 by down-regulating their transcription levels. In addition, CS extract suppressed the phosphorylation of ERK1/2, JNK, and p38 MAPK, and the nuclear translocation of NF-κB p65 in activated microglia. These results indicate that CS extract is capable of suppressing the inflammatory response by microglia activation, suggesting that CS extract has potential in the treatment of brain inflammation. Copyright © 2014 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.

Evidence of a New Role for the High-Osmolarity Glycerol Mitogen-Activated Protein Kinase Pathway in Yeast: Regulating Adaptation to Citric Acid Stress†

OpenAIRE

Lawrence, Clare L.; Botting, Catherine H.; Antrobus, Robin; Coote, Peter J.

2004-01-01

Screening the Saccharomyces cerevisiae disruptome, profiling transcripts, and determining changes in protein expression have identified an important new role for the high-osmolarity glycerol (HOG) mitogen-activated protein kinase (MAPK) pathway in the regulation of adaptation to citric acid stress. Deletion of HOG1, SSK1, PBS2, PTC2, PTP2, and PTP3 resulted in sensitivity to citric acid. Furthermore, citric acid resulted in the dual phosphorylation, and thus activation, of Hog1p. Despite mino...

Biomarkers and Stimulation Algorithms for Adaptive Brain Stimulation

Directory of Open Access Journals (Sweden)

Kimberly B. Hoang

2017-10-01

Full Text Available The goal of this review is to describe in what ways feedback or adaptive stimulation may be delivered and adjusted based on relevant biomarkers. Specific treatment mechanisms underlying therapeutic brain stimulation remain unclear, in spite of the demonstrated efficacy in a number of nervous system diseases. Brain stimulation appears to exert widespread influence over specific neural networks that are relevant to specific disease entities. In awake patients, activation or suppression of these neural networks can be assessed by either symptom alleviation (i.e., tremor, rigidity, seizures or physiological criteria, which may be predictive of expected symptomatic treatment. Secondary verification of network activation through specific biomarkers that are linked to symptomatic disease improvement may be useful for several reasons. For example, these biomarkers could aid optimal intraoperative localization, possibly improve efficacy or efficiency (i.e., reduced power needs, and provide long-term adaptive automatic adjustment of stimulation parameters. Possible biomarkers for use in portable or implanted devices span from ongoing physiological brain activity, evoked local field potentials (LFPs, and intermittent pathological activity, to wearable devices, biochemical, blood flow, optical, or magnetic resonance imaging (MRI changes, temperature changes, or optogenetic signals. First, however, potential biomarkers must be correlated directly with symptom or disease treatment and network activation. Although numerous biomarkers are under consideration for a variety of stimulation indications the feasibility of these approaches has yet to be fully determined. Particularly, there are critical questions whether the use of adaptive systems can improve efficacy over continuous stimulation, facilitate adjustment of stimulation interventions and improve our understanding of the role of abnormal network function in disease mechanisms.

Mitogen-activated protein kinases interacting kinases are autoinhibited by a reprogrammed activation segment.

Science.gov (United States)

Jauch, Ralf; Cho, Min-Kyu; Jäkel, Stefan; Netter, Catharina; Schreiter, Kay; Aicher, Babette; Zweckstetter, Markus; Jäckle, Herbert; Wahl, Markus C

2006-09-06

Autoinhibition is a recurring mode of protein kinase regulation and can be based on diverse molecular mechanisms. Here, we show by crystal structure analysis, nuclear magnetic resonance (NMR)-based nucleotide affinity studies and rational mutagenesis that nonphosphorylated mitogen-activated protein (MAP) kinases interacting kinase (Mnk) 1 is autoinhibited by conversion of the activation segment into an autoinhibitory module. In a Mnk1 crystal structure, the activation segment is repositioned via a Mnk-specific sequence insertion at the N-terminal lobe with the following consequences: (i) the peptide substrate binding site is deconstructed, (ii) the interlobal cleft is narrowed, (iii) an essential Lys-Glu pair is disrupted and (iv) the magnesium-binding loop is locked into an ATP-competitive conformation. Consistently, deletion of the Mnk-specific insertion or removal of a conserved phenylalanine side chain, which induces a blockade of the ATP pocket, increase the ATP affinity of Mnk1. Structural rearrangements required for the activation of Mnks are apparent from the cocrystal structure of a Mnk2 D228G -staurosporine complex and can be modeled on the basis of crystal packing interactions. Our data suggest a novel regulatory mechanism specific for the Mnk subfamily.

In vitro cell-mediated immunity assay using 125I-iododeoxyuridine

International Nuclear Information System (INIS)

Morris, J.E.; Graham, T.M.

1979-01-01

We investigated an in vitro cell-mediated immunity assay using incorporation of 125 I-iododeoxyuridine as an indicator of lymphocyte responsiveness to mitogen stimulation. The system permits the use of whole-blood cultures in rats and dogs

A distributed current stimulator ASIC for high density neural stimulation.

Science.gov (United States)

Jeong Hoan Park; Chaebin Kim; Seung-Hee Ahn; Tae Mok Gwon; Joonsoo Jeong; Sang Beom Jun; Sung June Kim

2016-08-01

This paper presents a novel distributed neural stimulator scheme. Instead of a single stimulator ASIC in the package, multiple ASICs are embedded at each electrode site for stimulation with a high density electrode array. This distributed architecture enables the simplification of wiring between electrodes and stimulator ASIC that otherwise could become too complex as the number of electrode increases. The individual ASIC chip is designed to have a shared data bus that independently controls multiple stimulating channels. Therefore, the number of metal lines is determined by the distributed ASICs, not by the channel number. The function of current steering is also implemented within each ASIC in order to increase the effective number of channels via pseudo channel stimulation. Therefore, the chip area can be used more efficiently. The designed chip was fabricated with area of 0.3 mm2 using 0.18 μm BCDMOS process, and the bench-top test was also conducted to validate chip performance.

Shared neuroanatomical substrates of impaired phonological working memory across reading disability and autism.

Science.gov (United States)

Lu, Chunming; Qi, Zhenghan; Harris, Adrianne; Weil, Lisa Wisman; Han, Michelle; Halverson, Kelly; Perrachione, Tyler K; Kjelgaard, Margaret; Wexler, Kenneth; Tager-Flusberg, Helen; Gabrieli, John D E

2016-03-01

Individuals with reading disability or individuals with autism spectrum disorder (ASD) are characterized, respectively, by their difficulties in reading or social communication, but both groups often have impaired phonological working memory (PWM). It is not known whether the impaired PWM reflects distinct or shared neuroanatomical abnormalities in these two diagnostic groups. White-matter structural connectivity via diffusion weighted imaging was examined in sixty-four children, ages 5-17 years, with reading disability, ASD, or typical development (TD), who were matched in age, gender, intelligence, and diffusion data quality. Children with reading disability and children with ASD exhibited reduced PWM compared to children with TD. The two diagnostic groups showed altered white-matter microstructure in the temporo-parietal portion of the left arcuate fasciculus (AF) and in the temporo-occipital portion of the right inferior longitudinal fasciculus (ILF), as indexed by reduced fractional anisotropy and increased radial diffusivity. Moreover, the structural integrity of the right ILF was positively correlated with PWM ability in the two diagnostic groups, but not in the TD group. These findings suggest that impaired PWM is transdiagnostically associated with shared neuroanatomical abnormalities in ASD and reading disability. Microstructural characteristics in left AF and right ILF may play important roles in the development of PWM. The right ILF may support a compensatory mechanism for children with impaired PWM.

Transcranial brain stimulation: closing the loop between brain and stimulation

DEFF Research Database (Denmark)

Karabanov, Anke; Thielscher, Axel; Siebner, Hartwig Roman

2016-01-01

-related and state-related variability. Fluctuations in brain-states can be traced online with functional brain imaging and inform the timing or other settings of transcranial brain stimulation. State-informed open-loop stimulation is aligned to the expression of a predefined brain state, according to prespecified......PURPOSE OF REVIEW: To discuss recent strategies for boosting the efficacy of noninvasive transcranial brain stimulation to improve human brain function. RECENT FINDINGS: Recent research exposed substantial intra- and inter-individual variability in response to plasticity-inducing transcranial brain...... stimulation. Trait-related and state-related determinants contribute to this variability, challenging the standard approach to apply stimulation in a rigid, one-size-fits-all fashion. Several strategies have been identified to reduce variability and maximize the plasticity-inducing effects of noninvasive...

Context Specificity of Stress-activated Mitogen-activated Protein (MAP) Kinase Signaling: The Story as Told by Caenorhabditis elegans.

Science.gov (United States)

Andrusiak, Matthew G; Jin, Yishi

2016-04-08

Stress-associated p38 and JNK mitogen-activated protein (MAP) kinase signaling cascades trigger specific cellular responses and are involved in multiple disease states. At the root of MAP kinase signaling complexity is the differential use of common components on a context-specific basis. The roundwormCaenorhabditis eleganswas developed as a system to study genes required for development and nervous system function. The powerful genetics ofC. elegansin combination with molecular and cellular dissections has led to a greater understanding of how p38 and JNK signaling affects many biological processes under normal and stress conditions. This review focuses on the studies revealing context specificity of different stress-activated MAPK components inC. elegans. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

The role of glutathione in lymphocyte activation and proliferation

International Nuclear Information System (INIS)

Messina, J.P.

1990-01-01

The object of this work was to establish the requirement for GSH and cystine during the activation and proliferation of human peripheral blood mononuclear cells (PBMC). In the author's initial experiments the intracellular GSH content of PBMC was altered by continuous culture or pretreatment with BSO, a specific inhibitor of GSH synthesis. His results demonstrate that, continuous culture of mitogen stimulated PBMC in the presence of BSO inhibited entry into S-phase of the cell cycle and produced a simultaneous decrease in intracellular GSH. The influence of BSO on early activation events were determined by BSO pretreatment. Extensive depletion (>90%) of the intracellular GSH level prior to mitogenic stimulation did not impair the ability of these cells to produce IL-2 and express IL-2R, indicating that GSH may not be involved in the generation and response to early activation signals. Furthermore, the removal of BSO from these cultures rapidly reversed its inhibitory effects on DNA and GSH synthesis. Cystine transport activities and metabolism by PBMC were characterized in order to examine its contributions to intracellular GSH and early activation proteins. In spite of the ability of cystine to sustain the proliferative response of PBMC, differences in the kinetics of cystine and cysteine uptake indicated that separate transport systems may be operational. Treatment with 2ME enhanced cystine uptake, but lowered the proliferative responses of these cells. Metabolic studies with [ 35 S] cystine demonstrated that mitogen stimulation of PBMC enhance cystine uptake

Plasticity of the MAPK signaling network in response to mechanical stress

NARCIS (Netherlands)

Pereira, Andrea M; Tudor, Cicerone; Pouille, Philippe-Alexandre; Shekhar, Shashank; Kanger, Johannes S; Subramaniam, Vinod; Martín-Blanco, Enrique

2014-01-01

Cells display versatile responses to mechanical inputs and recent studies have identified the mitogen-activated protein kinase (MAPK) cascades mediating the biological effects observed upon mechanical stimulation. Although, MAPK pathways can act insulated from each other, several mechanisms

Mitogen-Activated Protein Kinase 8 (MAP3K8) Mediates the Signaling Pathway of Estradiol Stimulating Progesterone Production Through G Protein-Coupled Receptor 30 (GPR30) in Mouse Corpus Luteum.

Science.gov (United States)

Liu, Ying; Li, Yueqin; Zhang, Di; Liu, Jiali; Gou, Kemian; Cui, Sheng

2015-05-01

The corpus luteum (CL) is a transient endocrine gland developed from the ovulated follicles, and the most important function is to synthesize and secrete progesterone (P(4)), a key hormone to maintain normal pregnancy and estrous cycle in most mammals. It is known that estrogen has a vital role in stimulating P(4) synthesis in CL, but it still remains unclear about the mechanism of estradiol (E(2)) regulating P(4) production in CL. Our results here first show that all of the CL cells express MAPK 8 (MAP3K8), and the MAP3K8 level is much higher at the midstage than at the early and late stages during CL development. The further functional studies show that the forced inhibition of endogenous MAP3K8 by using MAP3K8 small interfering RNA and MAP3K8 signaling inhibitor (MAP3K8i) in the luteal cells significantly block the P(4) synthesis and neutralize the enhancing effect of E(2) on P(4) production in the CL. In addition, our results here demonstrate that the stimulating effect of E(2) on P(4) synthesis relies on the estrogen no-classical protein-coupled receptor 30, and MAP3K8 is involved in mediating the protein-coupled receptor 30signaling of E(2) affecting P(4) synthesis via stimulating ERK phosphorylation. These novel findings are critical for our understanding the ovary physiology and pathological mechanism.

The Na+/H+ exchanger, NHE1, differentially regulates mitogen-activated protein kinase subfamilies after osmotic shrinkage in Ehrlich Lettre Ascites cells

DEFF Research Database (Denmark)

Petersen, Stine Helene Falsig; Rasmussen, Maria; Darborg, Barbara Vasek

2007-01-01

Osmotic stress modulates mitogen activated protein kinase (MAPK) activities, leading to altered gene transcription and cell death/survival balance, however, the mechanisms involved are incompletely elucidated. Here, we show, using a combination of biochemical and molecular biology approaches...... by human (h) NHE1 expression in cells lacking endogenous NHE1 activity. The effect of NHE1 on ERK1/2 was pH(i)-independent and upstream of MEK1/2. Shrinkage-activation of JNK1/2 was attenuated by EIPA, augmented by hNHE1 expression, and abolished in the presence of HCO(3)(-). Basal JNK activity...

Phytohemagglutinin (PHA) stimulation of peripheral-blood lymphocytes and stem cell take

Energy Technology Data Exchange (ETDEWEB)

Astaldi, G [Blood Research Foundation Center, Tortona, Italy; Karanovic, D; Vettori, P P; Karanovic, J; Piletic, O

1974-01-01

The effect of PHA-stimulation of peripheral-blood lymphocytes on the spleen-colony formation in irradiated rats was examined. 25-day old Wistar rats underwent total-body irradiation (600 R), and they were used as recipients. On the other hand, 2 and /sup 1///sub 2/ month old untreated Wistar rats were used as donors of peripheral-blood lymphocytes, which were obtained by sedimentation with Dextraven from defibrinated blood. Four rat lots were used. The 1st one did not receive irradiation, and was kept as ''blank control.'' The 2nd one was just irradiated and kept as ''radiated control.'' The 3rd and the 4th rat lots of the series were irradiated, but the former lot was injected i.v. with 5 x 10/sup 7/ peripheral-blood untreated lymphocytes, whereas the fourth lot was injected i.v. with the same amount of lymphocytes, which were previously incubated in vitro for 24 hrs with PHA-M (Difco). The results showed that the PHA-incubation of transplanted peripheral-blood lymphocytes significantly increases the number and size of the macroscopic spleen colonies, in relationship to the colonies which occurs after transplantation of untreated lymphocytes. Histo-cytological observation clearly showed that the colonies formed after injection of mitogen-pretreated peripheral-blood lymphocytes were predominantly of erythroid type and, then, of non-differentiated cells. Only a few of them were of a mixed type, consisting of both undifferentiated cells and erythroid cells.

Changes of the blood lymphocyte subpopulations and their functions following /sup 131/I treatment for nodular goitre and /sup 32/P treatment for polycythemia vera

Energy Technology Data Exchange (ETDEWEB)

Wasserman, J.; Petrini, B.; Stedingk, L.-V. von; Blomgren, H.; Svedmyr, E.; Schnell, P.-O.; Lundell, G.

1988-01-01

The blood lymphocyte population was examined in 34 patients treated with /sup 131/I for toxic or atoxic nodular goitre. One to three doses of 300-550 MBq of /sup 131/I were administered at 1-week intervals. Results, with the exception of mitogen reactivity, were largely similar to those occurring following external radiation therapy for cancer. It is suggested that blood lymphocytes passing through the continuously irradiated gland are damaged mainly by ..beta..-rays. The effect of /sup 32/P treatment on the blood lymphocyte population was examined in 16 patients with polycythemia vera. Following a single oral dose of /sup 32/P(150-305 MBq), which normalized the production of erythrocytes andor platelets, blood lymphocyte counts were reduced by approximately 40% 12 weeks after treatment. Examination of subsets demonstrated the proportion of B-cells was decreased by the highest relative extent, but lymphocytes expressing the T cell markers were increased. /sup 32/P treatment markedly increased PHA reactivity but further reduced PWM-induced Ig secreation, in agreement with the finding that serum concentrations of Ig were reduced after treatment. (U.K.)

Changes of the blood lymphocyte subpopulations and their functions following 131I treatment for nodular goitre and 32P treatment for polycythemia vera

International Nuclear Information System (INIS)

Wasserman, Jerzy; Petrini, Bjorn; Stedingk, L.-V. von; Blomgren, Henric; Svedmyr, Erik; Schnell, P.-O.; Lundell, G.

1988-01-01

The blood lymphocyte population was examined in 34 patients treated with 131 I for toxic or atoxic nodular goitre. One to three doses of 300-550 MBq of 131 I were administered at 1-week intervals. Results, with the exception of mitogen reactivity, were largely similar to those occurring following external radiation therapy for cancer. It is suggested that blood lymphocytes passing through the continuously irradiated gland are damaged mainly by β-rays. The effect of 32 P treatment on the blood lymphocyte population was examined in 16 patients with polycythemia vera. Following a single oral dose of 32 P(150-305 MBq), which normalized the production of erythrocytes and/or platelets, blood lymphocyte counts were reduced by approximately 40% 12 weeks after treatment. Examination of subsets demonstrated the proportion of B-cells was decreased by the highest relative extent, but lymphocytes expressing the T cell markers were increased. 32 P treatment markedly increased PHA reactivity but further reduced PWM-induced Ig secreation, in agreement with the finding that serum concentrations of Ig were reduced after treatment. (U.K.)

Vagal nerve stimulation therapy: what is being stimulated?

Science.gov (United States)

Kember, Guy; Ardell, Jeffrey L; Armour, John A; Zamir, Mair

2014-01-01

Vagal nerve stimulation in cardiac therapy involves delivering electrical current to the vagal sympathetic complex in patients experiencing heart failure. The therapy has shown promise but the mechanisms by which any benefit accrues is not understood. In this paper we model the response to increased levels of stimulation of individual components of the vagal sympathetic complex as a differential activation of each component in the control of heart rate. The model provides insight beyond what is available in the animal experiment in as much as allowing the simultaneous assessment of neuronal activity throughout the cardiac neural axis. The results indicate that there is sensitivity of the neural network to low level subthreshold stimulation. This leads us to propose that the chronic effects of vagal nerve stimulation therapy lie within the indirect pathways that target intrinsic cardiac local circuit neurons because they have the capacity for plasticity.

Vagal nerve stimulation therapy: what is being stimulated?

Directory of Open Access Journals (Sweden)

Guy Kember

Full Text Available Vagal nerve stimulation in cardiac therapy involves delivering electrical current to the vagal sympathetic complex in patients experiencing heart failure. The therapy has shown promise but the mechanisms by which any benefit accrues is not understood. In this paper we model the response to increased levels of stimulation of individual components of the vagal sympathetic complex as a differential activation of each component in the control of heart rate. The model provides insight beyond what is available in the animal experiment in as much as allowing the simultaneous assessment of neuronal activity throughout the cardiac neural axis. The results indicate that there is sensitivity of the neural network to low level subthreshold stimulation. This leads us to propose that the chronic effects of vagal nerve stimulation therapy lie within the indirect pathways that target intrinsic cardiac local circuit neurons because they have the capacity for plasticity.

Three-Level Inverters with Common-Mode Voltage Cancellation Based on Synchronous Pulsewidth Modulation

DEFF Research Database (Denmark)

Oleschuk, Valentin; Blaabjerg, Frede

2002-01-01

A novel method of direct synchronous pulse-width modulation (PWM) is disseminated to three-level voltage source inverters with control algorithms with elimination of the common-mode voltages in three-phase drive systems with PWM. It provides smooth pulses-ratio changing and a quarter-wave symmetry...... of the voltage waveforms during the whole control range including overmodulation. Continuous, discontinuous and "direct-direct" schemes of synchronous PWM with both algebraic and trigonometric control functions have been analysed and compared. Simulations give the behaviour of the proposed methods and show some...... advantages of synchronous PWM in comparison with asynchronous at low ratios between the switching frequency and fundamental frequency....

Synchronised Voltage Space Vector Modulation for Three-level Inverters with Common-mode Voltage Elimination

DEFF Research Database (Denmark)

Oleschuk, Valentin; Blaabjerg, Frede

2002-01-01

A novel method of direct synchronous pulse-width modulation (PWM) is disseminated to three-level voltage source inverters with control algorithms with elimination of the common-mode voltages in three-phase drive systems with PWM. It provides smooth pulses-ratio changing and a quarter-wave symmetry...... of the voltage waveforms during the whole control range including overmodulation. Continuous, discontinuous and "direct-direct" schemes of synchronous PWM with both algebraic and trigonometric control functions have been analysed and compared. Simulations give the behaviour of the proposed methods and show some...... advantages of synchronous PWM in comparison with asynchronous at low ratios between the switching frequency and fundamental frequency....

p38 mitogen-activated protein kinase up-regulates LPS-induced NF-κB activation in the development of lung injury and RAW 264.7 macrophages

International Nuclear Information System (INIS)

Kim, Hee J.; Lee, Hui S.; Chong, Young H.; Kang, Jihee Lee

2006-01-01

Clarification of the key regulatory steps that lead to nuclear factor-kappa B (NF-κB) under cellular and pathological conditions is very important. The action of p38 mitogen-activated protein kinase (MAPK) on the upstream of NF-κB activation remains controversial. To examine this issue using an in vivo lung injury model, SB203580, a p38 MAPK inhibitor was given intraorally 1 h prior to lipopolysaccharide (LPS) treatment (intratracheally). The mice were sacrificed 4 h after LPS treatment. SB203580 substantially suppressed LPS-induced rises in p38 MAPK phosphorylation, neutrophil recruitment, total protein content in bronchoalveolar lavage fluid, and apoptosis of bronchoalveolar cells. Furthermore, SB203580 blocked LPS-induced NF-κB activation in lung tissue through down-regulation of serine phosphorylation, degradation of IκB-α, and consequent translocation of the p65 subunit of NF-κB to the nucleus. It is likely that, in cultured RAW 264.7 macrophages, SB203580 also blocked LPS-induced NF-κB activation in a dose-dependent manner. SB203580 inhibited LPS-induced serine phosphorylation, degradation of IκB-α, and tyrosine phosphorylation of p65 NF-κB. These data indicate that p38 MAPK acts upstream of LPS-induced NF-κB activation by modulating the phosphorylation of IκB-α and p65 NF-κB during acute lung injury. Because LPS-stimulated macrophages may contribute to inflammatory lung injury, the inhibition of the p38 MAPK-mediated intracellular signaling pathway leading to NF-κB activation represents a target for the attenuation of lung inflammation and parenchymal damage

Immunodeficiency after allogeneic bone marrow transplantation in man. Effect of phorbol ester (phorbol myristate acetate) and calcium ionophore (A23187) in vitro

DEFF Research Database (Denmark)

Møller, J; Hofmann, B; Langhoff, E

1989-01-01

This study was undertaken to clarify the mechanism behind the severely decreased lymphocyte proliferative response upon stimulation with mitogens and antigens seen after allogeneic bone marrow transplantation (BMT) in man. We investigated eight BMT patients and eight controls and found...

Immunomodulatory capacity of fungal proteins on the cytokine production of human peripheral blood mononuclear cells

NARCIS (Netherlands)

Jeurink, P.V.; Lull Noguera, C.; Savelkoul, H.F.J.; Wichers, H.J.

2008-01-01

Immunomodulation by fungal compounds can be determined by the capacity of the compounds to influence the cytokine production by human peripheral blood mononuclear cells (hPBMC). These activities include mitogenicity, stimulation and activation of immune effector cells. Eight mushroom strains

A novel dual-wavelength laser stimulator to elicit transient and tonic nociceptive stimulation.

Science.gov (United States)

Dong, Xiaoxi; Liu, Tianjun; Wang, Han; Yang, Jichun; Chen, Zhuying; Hu, Yong; Li, Yingxin

2017-07-01

This study aimed to develop a new laser stimulator to elicit both transient and sustained heat stimulation with a dual-wavelength laser system as a tool for the investigation of both transient and tonic experimental models of pain. The laser stimulator used a 980-nm pulsed laser to generate transient heat stimulation and a 1940-nm continuous-wave (CW) laser to provide sustained heat stimulation. The laser with 980-nm wavelength can elicit transient pain with less thermal injury, while the 1940-nm CW laser can effectively stimulate both superficial and deep nociceptors to elicit tonic pain. A proportional integral-derivative (PID) temperature feedback control system was implemented to ensure constancy of temperature during heat stimulation. The performance of this stimulator was evaluated by in vitro and in vivo animal experiments. In vitro experiments on totally 120 specimens fresh pig skin included transient heat stimulation by 980-nm laser (1.5 J, 10 ms), sustained heat stimulation by 1940-nm laser (50-55 °C temperature control mode or 1.5 W, 5 min continuous power supply), and the combination of transient/sustained heat stimulation by dual lasers (1.5 J, 10 ms, 980-nm pulse laser, and 1940-nm laser with 50-55 °C temperature control mode). Hemoglobin brushing and wind-cooling methods were tested to find better stimulation model. A classic tail-flick latency (TFL) experiment with 20 Wistar rats was used to evaluate the in vivo efficacy of transient and tonic pain stimulation with 15 J, 100 ms 980-nm single laser pulse, and 1.5 W constant 1940-nm laser power. Ideal stimulation parameters to generate transient pain were found to be a 26.6 °C peak temperature rise and 0.67 s pain duration. In our model of tonic pain, 5 min of tonic stimulation produced a temperature change of 53.7 ± 1.3 °C with 1.6 ± 0.2% variation. When the transient and tonic stimulation protocols were combined, no significant difference was observed depending on the order

Modulation of Cyclins, p53 and Mitogen-Activated Protein Kinases Signaling in Breast Cancer Cell Lines by 4-(3,4,5-Trimethoxyphenoxybenzoic Acid

Directory of Open Access Journals (Sweden)

Kuan-Han Lee

2014-01-01

Full Text Available Despite the advances in cancer therapy and early detection, breast cancer remains a leading cause of cancer-related deaths among females worldwide. The aim of the current study was to investigate the antitumor activity of a novel compound, 4-(3,4,5-trimethoxyphenoxybenzoic acid (TMPBA and its mechanism of action, in breast cancer. Results indicated the relatively high sensitivity of human breast cancer cell-7 and MDA-468 cells towards TMPBA with IC50 values of 5.9 and 7.9 µM, respectively compared to hepatocarcinoma cell line Huh-7, hepatocarcinoma cell line HepG2, and cervical cancer cell line Hela cells. Mechanistically, TMPBA induced apoptotic cell death in MCF-7 cells as indicated by 4',6-diamidino-2-phenylindole (DAPI nuclear staining, cell cycle analysis and the activation of caspase-3. Western blot analysis revealed the ability of TMPBA to target pathways mediated by mitogen-activated protein (MAP kinases, 5' adenosine monophosphate-activated protein kinase (AMPK, and p53, of which the concerted action underlined its antitumor efficacy. In addition, TMPBA induced alteration of cyclin proteins’ expression and consequently modulated the cell cycle. Taken together, the current study underscores evidence that TMPBA induces apoptosis in breast cancer cells via the modulation of cyclins and p53 expression as well as the modulation of AMPK and mitogen-activated protein kinases (MAPK signaling. These findings support TMPBA’s clinical promise as a potential candidate for breast cancer therapy.

Regulation of microglia activity by glaucocalyxin-A: attenuation of lipopolysaccharide-stimulated neuroinflammation through NF-κB and p38 MAPK signaling pathways.

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Byung-Wook Kim

Full Text Available Microglial cells are the resident macrophages and intrinsic arm of the central nervous system innate immune defense. Microglial cells become activated in response to injury, infection, environmental toxins, and other stimuli that threaten neuronal survival. Therefore, regulating microglial activation may have therapeutic benefits that lead to alleviating the progression of inflammatory-mediated neurodegeneration. In the present study, we investigated the effect of glaucocalyxin A (GLA isolated from Rabdosia japonica on the production of pro-inflammatory mediators in lipopolysaccharide (LPS-stimulated primary microglia and BV-2 cells. GLA significantly inhibited LPS-induced production of nitric oxide and reversed the morphological changes in primary microglia. Further, GLA suppressed expression of inducible nitric oxide synthase and cyclooxygenase-2 dose-dependently at the mRNA and protein levels. The production of proinflammatory cytokines such as tumor necrosis factor-α, interleukin-1β (IL-1β, and IL-6 were inhibited by suppressing their transcriptional activity. Furthermore, GLA suppressed nuclear factor-κB activation by blocking degradation of IκB-α and inhibited the induction of lipocalin-2 expression in LPS-stimulated BV-2 cells. Mechanistic study revealed that the inhibitory effects of GLA were accompanied by blocking the p38 mitogen activated protein kinase signaling pathway in activated microglia. In conclusion, given that microglial activation contributes to the pathogenesis of neurodegenerative diseases, GLA could be developed as a potential therapeutic agent for treating microglia-mediated neuroinflammatory diseases.

Higher moments method for generalized Pareto distribution in flood frequency analysis

Science.gov (United States)

Zhou, C. R.; Chen, Y. F.; Huang, Q.; Gu, S. H.

2017-08-01

The generalized Pareto distribution (GPD) has proven to be the ideal distribution in fitting with the peak over threshold series in flood frequency analysis. Several moments-based estimators are applied to estimating the parameters of GPD. Higher linear moments (LH moments) and higher probability weighted moments (HPWM) are the linear combinations of Probability Weighted Moments (PWM). In this study, the relationship between them will be explored. A series of statistical experiments and a case study are used to compare their performances. The results show that if the same PWM are used in LH moments and HPWM methods, the parameter estimated by these two methods is unbiased. Particularly, when the same PWM are used, the PWM method (or the HPWM method when the order equals 0) shows identical results in parameter estimation with the linear Moments (L-Moments) method. Additionally, this phenomenon is significant when r ≥ 1 that the same order PWM are used in HPWM and LH moments method.

Antiepileptic Effect of Uncaria rhynchophylla and Rhynchophylline Involved in the Initiation of c-Jun N-Terminal Kinase Phosphorylation of MAPK Signal Pathways in Acute Seizures of Kainic Acid-Treated Rats

OpenAIRE

Hsu, Hsin-Cheng; Tang, Nou-Ying; Liu, Chung-Hsiang; Hsieh, Ching-Liang

2013-01-01

Seizures cause inflammation of the central nervous system. The extent of the inflammation is related to the severity and recurrence of the seizures. Cell surface receptors are stimulated by stimulators such as kainic acid (KA), which causes intracellular mitogen-activated protein kinase (MAPK) signal pathway transmission to coordinate a response. It is known that Uncaria rhynchophylla (UR) and rhynchophylline (RP) have anticonvulsive effects, although the mechanisms remain unclear. Therefore,...

Cognitive stimulation in healthy older adults: a cognitive stimulation program using leisure activities compared to a conventional cognitive stimulation program.

Science.gov (United States)

Grimaud, Élisabeth; Taconnat, Laurence; Clarys, David

2017-06-01

The aim of this study was to compare two methods of cognitive stimulation for the cognitive functions. The first method used an usual approach, the second used leisure activities in order to assess their benefits on cognitive functions (speed of processing; working memory capacity and executive functions) and psychoaffective measures (memory span and self esteem). 67 participants over 60 years old took part in the experiment. They were divided into three groups: 1 group followed a program of conventional cognitive stimulation, 1 group a program of cognitive stimulation using leisure activities and 1 control group. The different measures have been evaluated before and after the training program. Results show that the cognitive stimulation program using leisure activities is as effective on memory span, updating and memory self-perception as the program using conventional cognitive stimulation, and more effective on self-esteem than the conventional program. There is no difference between the two stimulated groups and the control group on speed of processing. Neither of the two cognitive stimulation programs provides a benefit over shifting and inhibition. These results indicate that it seems to be possible to enhance working memory and to observe far transfer benefits over self-perception (self-esteem and memory self-perception) when using leisure activities as a tool for cognitive stimulation.

Parameters of the labeling of mitogen-activated murine lymphocytes by [35S]methionine for two-dimensional gel electrophoresis. I

International Nuclear Information System (INIS)

Kettman, J.R.

1986-01-01

Labeling with [ 35 S]methionine at a high specific activity is essential to the facile preparation of 2-dimensional gel electrophoretograms with the analytical 2-dimensional charge-size separation procedure. Mitogen-activated T and B lymphocytes subjected to low methionine concentrations would not proceed through cell cycle. In the case of activated B lymphocytes, the use of fetal bovine serum, dialyzed to lower endogenous methionine concentrations, prevented B cell growth even in the presence of otherwise satisfactory levels of methionine. High concentrations of [ 35 S]methionine induced B cell death, apparently by radiation damage. Despite these problems, good radioautograms and radiofluorograms of 2D electrophoretograms could be prepared by labeling activated B or T cells in bulk with high specific activity [ 35 S]methionine. (Auth.)

Expression of MMPs is dependent on the activity of mitogen-activated protein kinase in chondrosarcoma.

Science.gov (United States)

Yao, Min; Wang, Xiaomei; Zhao, Yufeng; Wang, Xiaomeng; Gao, Feng

2017-02-01

Matrix metalloproteinases (MMPs) and tissue inhibitors of matrix metalloproteinases (TIMPs) serve an important role in chondrosarcoma. The present study investigated whether the expression of MMPs was dependent on the activity of mitogen-activated protein kinase (MAPK) in chondrosarcoma. Surgical pathological specimens were collected to detect MMP-1, MMP-13, TIMP-1, type II collagen and phosphorylated MAPK levels in normal cartilage, enchondroma and chondrosarcoma tissues. The expression of MMP‑1, MMP‑13, TIMP‑1 and type II collagen was investigated utilizing MAPK inhibitors in chondrosarcoma cells. It was noted that the expression levels of MMP‑1, MMP‑13 and TIMP‑1 were increased in chondrosarcoma with the activity of MAPK. After chondrosarcoma cells were pretreated with MAPK inhibitors, the levels of MMP‑1, MMP‑13 and TIMP‑1 were inhibited. Furthermore, MMP‑1 and MMP‑13 are essential in regulating the degradation of type II collagen and decomposing cartilage matrix major. The high expression levels of MMP‑1 and MMP‑13 in chondrosarcoma expedite the invasion by chondrosarcoma cells and their expression can be depressed by MAPK inhibitors.

Bioactive glass induced osteogenic differentiation of human adipose stem cells is dependent on cell attachment mechanism and mitogen-activated protein kinases

Directory of Open Access Journals (Sweden)

M Ojansivu

2018-02-01

Full Text Available Bioactive glasses (BaGs are widely utilised in bone tissue engineering (TE but the molecular response of cells to BaGs is poorly understood. To elucidate the mechanisms of cell attachment to BaGs and BaG-induced early osteogenic differentiation, we cultured human adipose stem cells (hASCs on discs of two silica-based BaGs S53P4 (23.0 Na2O - 20.0 CaO - 4.0 P2O5 - 53.0 SiO2 (wt-% and 1-06 (5.9 Na2O - 12.0 K2O - 5.3 MgO - 22.6 CaO - 4.0 P2O5 - 0.2 B2O3 - 50.0 SiO2 in the absence of osteogenic supplements. Both BaGs induced early osteogenic differentiation by increasing alkaline phosphatase activity (ALP and the expression of osteogenic marker genes RUNX2a and OSTERIX. Based on ALP activity, the slower reacting 1-06 glass was a stronger osteoinducer. Regarding the cell attachment, cells cultured on BaGs had enhanced integrinβ1 and vinculin production, and mature focal adhesions were smaller but more dispersed than on cell culture plastic (polystyrene. Focal adhesion kinase (FAK, extracellular signal-regulated kinase (ERK1/2 and c-Jun N-terminal kinase (JNK-induced c-Jun phosphorylations were upregulated by glass contact. Moreover, the BaG-stimulated osteoinduction was significantly reduced by FAK and mitogen-activated protein kinase (MAPK inhibitors, indicating an important role for FAK and MAPKs in the BaG-induced early osteogenic commitment of hASCs. Upon indirect insert culture, the ions released from the BaG discs could not reproduce the observed cellular changes, which highlighted the role of direct cell-BaG interactions in the osteopotential of BaGs. These findings gave valuable insight into the mechanism of BaG-induced osteogenic differentiation and therefore provided knowledge to aid the future design of new functional biomaterials to meet the increasing demand for clinical bone TE treatments.

Mitogenic activity of pine cone extracts against cultured splenocytes from normal and tumor-bearing animals.

Science.gov (United States)

Kurakata, Y; Sakagami, H; Takeda, M; Konno, K; Kitajima, K; Ichikawa, S; Hata, N; Sato, T

1989-01-01

An acidic pine cone extract, Fr. V. of Pinus parviflora Sieb. et Zucc. significantly stimulated DNA synthesis of isolated splenocytes from both mice and rats, but only marginally affected the DNA synthesis of leukemic cell lines. The maximum stimulation level attained by Fr. V slightly exceeded that of plant lectins, whereas much weaker stimulating activity was found in natural and chemically modified antitumor polysaccharides, sialic acid-rich glycoproteins, and polyphenolic compounds such as lignin and tannic acid. In mice with subcutaneously transplanted sarcoma-180, responses of splenocytes against Con A declines in the terminal stage of tumor development, whereas responses against Fr. V remained relatively constant throughout all periods of tumor progression. The suppression of Fr. V activity by acetylation or methylation suggests the importance of the hydroxyl group in the expression of its stimulation activity.

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Indian Academy of Sciences (India)

Wnt signaling is involved in multiple developmental events during embryogenesis and is implicated in adult tissue maintenance. Wnt signaling is pleiotropic with effects that include mitogenic stimulation, cell fate specification and differentiation Perturbation in Wnt signaling promote both human neurogenerative disorders ...