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Kato et al. BMC Immunology 2014, 15:39 http://www.biomedcentral.com/1471-2172/15/39
β2 adrenergic agonist attenuates house dust mite-induced allergic airway inflammation through dendritic cells Go Kato1, Koichiro Takahashi1*, Hiroki Tashiro1, Keigo Kurata2, Hideharu Shirai2, Shinya Kimura1 and Shinichiro Hayashi1
Abstract Background: Long-acting β2 adrenergic agonists (LABAs) are commonly used combined with inhaled corticosteroids (ICS) to treat asthmatic patients. Previous reports suggest that LABAs have an anti-inflammatory effect in bronchial asthma, and this should be further investigated. The aim of this study was to investigate whether LABAs inhibit allergic airway inflammation and how this occurs. Results: We assessed the effect of the LABA formoterol (FORM) on inflammatory cell responses in airway, lung and regional lymph nodes, using an HDM-induced murine allergic asthma model in vivo. The effect of FORM on cytokine production from bone marrow derived dendritic cells (BMDCs) stimulated with HDM was evaluated in vitro. Adoptive transfer of BMDCs pulsed with HDM in the presence or absence of FORM to naïve mice was performed and the inflammatory response to subsequent HDM challenge was analyzed. FORM treatment suppressed HDM-induced changes and caused an increase in the number of eosinophils and neutrophils in bronchoalveolar lavage. The concentration of IL-4 and IL-17 in lung tissue homogenate was elevated and led to an accumulation of IL-4, IL-13, IL-5 and IL-17 producing cells in regional lymph nodes. FORM inhibited the production of IL-6 and IL-23 from BMDCs stimulated with HDM in vitro, and enhanced IL-10 production. The BMDCs adoptive transfer experiment indicated that dendritic cells mediate the effect of FORM, since FORM treatment of BMDCs in vitro attenuated airway inflammation. Conclusion: These results suggested that FORM modulates dendritic cell function and attenuates Th2 and Th17 responses induced by HDM. Thus, we propose that the clinical significance of LABAs should be re-investigated taking into account these immune-modulating effects. Keywords: Bronchial asthma, β2 adrenergic agonist, House dust mite, Dendritic cells
Background Bronchial asthma is a chronic airway inflammation associated with inhaled allergens including those produced by house dust mites (HDM) [1,2], and other environmental materials [3]. The pathophysiology of bronchial asthma is characterized by bronchoconstriction, airway hyper-responsiveness, and airway remodeling [4-6]. Although airway eosinophilia is a hallmark of bronchial asthma, the inflammatory process is mediated mainly by Th2 type lymphocytes [7,8]. Recently, evidence has been * Correspondence: [email protected] 1 Division of Hematology, Respiratory Medicine and Oncology, Department of Internal Medicine, Faculty of Medicine, Saga University, 5-1-1 Nabeshima, Saga 849-8501, Japan Full list of author information is available at the end of the article
accumulating that Th17 lymphocytes and their products, such as interleukin-17 (IL-17), mediate neutrophilic inflammation which plays an important role in severe asthma [9,10]. Dendritic cells (DCs) are responsible for the initial antigen-induced immune response, as they act as antigen presenting cells (APC) [11]. In the airways, DCs are present in the subepithelial region and process and present exogenous antigens. Naïve T cells recognize the antigen presented on DCs and differentiate into helper T cells [12,13]. Cytokines produced from DCs determine the direction of helper T cell differentiation and regulate characteristics of the inflammatory response [14]. In this
© 2014 Kato et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
aspect, DCs are a fascinating target for controlling allergic diseases such as bronchial asthma. Combination therapy with inhaled corticosteroids (ICS) and long acting β2 adrenergic agonists (LABAs) is generally used for the treatment of asthma [15]. The addition of LABAs to moderate doses of ICS has been reported to have greater benefit than double doses of ICS in symptomatic asthmatic patients [16]. Some explanations for this observation have been proposed. Firstly, drug delivery of ICS is improved by LABAs. Secondly, LABAs enhance the function of glucocorticoid receptors in airway smooth muscle cells and epithelial cells [17]. It is also possible that LABAs attenuate inflammatory cell responses [15,18], although the precise mechanism for this requires further clarification. The function of LABAs is mediated by the β2 adrenergic receptor (ADR) expressed on numerous cell types, including immune cells [19]. The APC activity of Langerhans cells in the skin was suppressed by epinephrine and norepinephrine through β2 ADR [20]. Conversely, Yanagawa and colleagues reported that β2 ADR stimulation enhanced IL-33 production by DCs, and referred to a possible role of β2 agonists in the stress-related progression of Th2-associated disorders [21]. Based on these findings, we aimed to investigate the impact of β2 adrenergic agonists, especially an LABA, on the function of DCs in an HDM-induced allergic airway inflammation model. This is the first report of an LABA significantly suppressing allergic airway inflammation through DCs.
Methods Allergen and chemicals
Protocol for HDM induced airway inflammation model
Mice were inoculated intranasally with 25 μg HDM or vehicle on days 0, 7 and 14. Mice were challenged intranasally with 5 μg HDM on days 21, 22 and 23. On day 24, mice were euthanized by intraperitoneal injection of sodium pentobarbital. Serum, bronchoalveolar lavage (BAL) fluid and lung tissue were harvested for further analysis (Figure 1a). FORM (12.5 ng/animal) was administered subcutaneously three times per week. FORM was dissolved in ethanol 10 mg/ml as a central stock, then was diluted optimal concentration using PBS. On the day when HDM was given, FORM was administered 30 minutes before the HDM inoculation. Collection of blood and BAL fluid
Blood and BAL fluid samples were collected as described previously [22]. Briefly, blood was collected by right ventricle puncture. Serum was collected by centrifugation of whole blood at 8,000 × g for 5 min at 4°C and stored at −80°C until needed. Then a 20-gauge tube was inserted into the trachea and the lungs were lavaged twice with 1.0 ml of saline. The cell suspension was centrifuged at 100 × g for 5 min at 4°C. The total number of cells was counted using a hemocytometer. Cytospin samples were prepared from the cell suspension. Cell differentiation was determined by counting at least 300 leukocytes in samples stained with Diff-Quik (Siemens, Germany). Histology
Histological examination was performed as previously reported [23]. Lungs were fixed with 10% neutralized buffered formalin (Wako, Osaka, Japan) and embedded in paraffin. Lung sections were stained with Hematoxylin and Eosin (H&E), and periodic acid-Schiff (PAS) stains.
Two batches of house dust mite (HDM) extract from Dermatophagoides farina (Der f) were provided by ITEA Inc. (Tokyo, Japan) as a lyophilized preparation of milled mites. Formoterol (FORM) was provided by Astellas Pharma Inc. (Tokyo, Japan). ADR antagonists used were propranolol for β1 + β2, ICI118,551 for β2, CGP20712A for β1, prazosin for α1 and yohimbine for α2-ADR respectively (Sigma-Aldrich Co. LLC., St. Louis, MO). Phenylmethylsulfonyl fluoride (PMSF), aprotinin, leupeptin, epinephrine, phorbol 12-myristate 13-acetate (PMA) and ionomycin were purchased from Sigma-Aldrich Co. LLC.
After bronchoalveolar lavage, the left lung was isolated and homogenized in 50 mM Tris buffered saline (pH 7.4) containing 1 mM EDTA, 1 mM PMSF, 1 μg/ml aprotinin, 1 μg/ml leupeptin, 1 mM Na3VO4 and 1 mM NaF. The lung homogenates were centrifuged at 10,000 × g for 15 min, and then supernatants were collected and stored at −80°C until required.
Lymphocyte stimulation in vitro
Female BALB/c mice (6–8 weeks old, Japan SLC Inc., Hamamatsu Japan) were maintained at the Saga University animal facility under specific pathogen free conditions. Animal experiments were undertaken following the guidelines for care and use of experimental animals of the Japanese Association for Laboratory Animals Science (1987) and were approved by the Saga University Animal Care and Use Committee.
Mice were inoculated intranasally with HDM or vehicle as described above on days 0, 7 and 14. A bronchial lymph node was removed on day 17, crushed gently and a single cell suspension prepared by passing through a 40 μm nylon mesh (BD Falcon, Franklin Lakes, NJ). Lymphocytes were stimulated with 25 ng/ml PMA and 1 μg/ml ionomycin for 4 hours. After stimulation, supernatants were collected and stored at −80°C.
Preparation of lung homogenate
Figure 1 Protocols for the HDM-induced airway inflammation model. (a) HDM-induced airway inflammation model. Female BALB/c mice were sensitized three times intranasally with 25 μg HDM at days 0, 7 and 14, and challenged three times intranasally with 5 μg HDM at days 21–23. Twenty-four hours after the final challenge, blood samples, BAL fluid and lung tissues were collected. BALB/c mice receiving PBS at sensitization and challenge were used as controls. (b) BM cells were harvested from BALB/c mice. DCs were generated by culturing BM cells with 10% FBS and 10 ng/ml GM-CSF in the culture medium for 7 days. On day 7, DCs were stimulated with HDM or HDM + FORM or PBS (control) for 24 hours. One million DCs were intranasally injected into BALB/c mice on the following day. After 10 days, recipient mice were challenged intranasally with 25 μg HDM. Twenty-four hours after the injection, blood samples, BAL fluid and lung tissues were collected. BALB/c mice receiving unstimulated DCs served as controls.
Measurement of cytokines by ELISA
IL-4, IL-6, IL-10, IL-13, IL-5, IL-17 and IL-23 were measured using a Quantikine ELISA Kit (R&D systems Inc., Minneapolis, MN) according to the manufacturer's instructions. All samples were measured in duplicate. Preparation of bone marrow derived dendritic cells and in vitro stimulation
Bone marrow (BM) cells were isolated from BALB/c mice as previously reported [24]. BM cells were resuspended at 2.0 × 106 cells/ml in RPMI1640 medium supplemented with 10% fetal calf serum (FCS). The cells were cultured in the presence of 10 ng/ml recombinant murine GMCSF (R&D systems) at 37°C in a humidified atmosphere containing 5% CO2 for 6 days. On day 6, cells were
harvested. More than 95% of the cells were positively stained with CD11c, and were used as myeloid dendritic cells (BMDCs) in the following experiments. BMDCs were stimulated with 10 μg/ml HDM, with or without FORM or epinephrine, for 24 hours. BMDCs were pretreated with 1 μM of propranolol, ICI118,551, CGP20712A, prazosin or yohimbine. BMDC supernatants were collected and stored at −80°C. Adoptive transfer of BMDCs
As shown in Figure 1b, BMDCs were stimulated with 10 μg/ml HDM, with or without 100 pM FORM for 24 hours. BMDCs were collected and washed twice, and then 1.0 × 106 BMDCs were administered to naïve BALB/ c mice intranasally. On day 10, mice were challenged with
25 μg HDM. Twenty four hours later, BAL fluid and bronchial lymph nodes were collected as described above. Lymphocytes were stimulated with 25 ng/ml PMA and 1 μg/ml ionomycin for 4 hours. After stimulation, supernatants were collected and stored at −80°C. Measurement of serum Der f specific IgG
To measure Der f-specific IgG, MaxiSorp plates (Nunc, Roskilde, Denmark) were coated with 0.25 μg/ml Der f (Seikagaku co. Tokyo). Plates were washed with 0.1 M phosphate-buffered saline (PBS) containing 0.05% Tween 20. Each well was filled with a blocking solution of 1% BSA (Sigma-Aldrich) in PBS, and incubated for 1 hour. After washing 3 times, 100 μl/well of serum was added and the plates incubated for 1 hour. After washing, IgG1 bound to the plate was detected using biotin-labeled rat anti-mouse IgG1 (Bio-Rad AbD Serotec Ltd, Oxford UK), HRP-streptavidin (Sigma-Aldrich), and 3,3',5,5'-tetramethylbenzidine (TMB, Invitrogen, CA). The amount of specific antibody was expressed as laboratory units (LU), and samples were compared with a standard serum containing Der f-specific IgG1. Statistical analysis
The data are shown as mean ± standard deviation (SD). Analysis of variance (ANOVA) was used for multiple comparison of continuous variables. When there was a significant difference, the difference between each group was tested using Scheffe's test. All tests were two-sided with a five percent level of significance.
concentration of IL-13 (118.4 ± 61.4 pg/ml in FORM v.s. 168.9 ± 39.8 pg/ml in HDM ), IL-5 (17.8 ± 7.6 pg/ml in FORM v.s. 21.9 ± 6.5 pg/ml in HDM )in lung tissue respectively (Figure 2d, 2e). The titer of serum HDM specific IgG in FORM mice (920.7 ± 600.3 LU/ml) was similar to that in the serum of HDM mice (1,270.0 ± 920.5 LU/ml) (Figure 2g). FORM treatment decreased Th2 and Th17 lymphocytes in bronchial lymph nodes
We next examined whether FORM attenuates the T cell response to HDM in regional lymph nodes. HDM treatment caused an increase in the concentration of IL-4, IL-13 and IL17 in supernatant of lymphocytes (Figure 3). Lymphocytes from FORM treated mice produced significantly less cytokines; IL-4; 104.7 ± 2.8 and 91.5 ± 3.9 pg/ml (p < 0.01), IL-13; 205.7 ± 14.3 and 103.6 ± 4.3 pg/ml (p < 0.01), IL-5; 37.4 ± 2.5 and 21.1 ± 3.0 pg/ml (p < 0.01), and IL-17, 94.7 ± 15.4 and 58.5 ± 2.2 pg/ml (p < 0.01), in HDM and HDM/FORM treated mice, respectively. These finding suggest that FORM attenuates the Th2 and Th17 responses to HDM in vivo. To eliminate the possibility that FORM directly affects cytokine production from lymphocytes, lymph node cells harvested from HDM mice were stimulated with PMA and ionomycin in the presence of various concentrations of FORM in vitro. As shown in Table 1, FORM concentrations of up to 10,000 pM did not alter IL-4, IL-13 or IL-17 production from lymphocytes. FORM modulated cytokine production from DCs
Results Formoterol treatment suppressed HDM-induced airway inflammation
We investigated the effect of the β2 adrenergic agonist, FORM, on HDM-induced airway inflammation. Mice were sensitized and challenged with HDM, which resulted in an increase of total cells, neutrophils, lymphocytes and eosinophils in BAL fluid. FORM treatment significantly suppressed BAL cell numbers (Figure 2a). Differences between the two groups were as follows; total number of cells; 16.3 ± 5.3 and 5.3 ± 2.4 × 104/ml (p < 0.01), neutrophils; 5.4 ± 2.9 and 1.4 ± 1.0 × 104/ml (p < 0.01), lymphocytes; 0.9 ± 0.8 and 0.5 ± 0.4 × 104/ml (p = 0.45), and eosinophils; 2.8 ± 1.6 and 0.5 ± 0.6 × 104/ml (p < 0.01) in HDM mice and FORM treated mice, respectively. Histological examination showed that inflammatory cell infiltration and goblet cell metaplasia were suppressed by FORM (Figure 2b). The concentrations of IL-4 and IL-17 in lung tissue were significantly decreased in FORM treated mice (Figure 2c, 2f). IL-4 concentration was 19.8 ± 2.9 and 9.1 ± 3.3 pg/ml (p < 0.01) and IL-17 was 143.6 ± 63.1 and 47.4 ± 33.5 pg/ml (p < 0.01) in HDM mice and FORM treated mice, respectively. There was no difference in the
We hypothesized that the suppression of T cell responses by FORM in vivo was mediated by DCs. We therefore examined the effect of FORM on cytokine production by BMDCs in vitro. BMDCs produced IL23 and IL-6 after HDM stimulation. IL-23 production was suppressed by both FORM and epinephrine in a dose dependent manner (Figure 4a), where the effect of FORM was 10,000 times stronger than epinephrine. IL-6 production was also suppressed by FORM, but not by epinephrine at concentrations of up to 10−7 M (Figure 4b). IL-10 production from DCs was enhanced by FORM and epinephrine in a dose dependent manner (Figure 4c). The effect of FORM on BMDCs was mediated by β2 ADR
We examined whether the effect of FORM is mediated specifically by ADR. To clarify which ADR contribute to the suppression of cytokine production by FORM, specific ADR antagonists used were propranolol for β1 + β2, ICI118,551 for β2, CGP20712A for β1, prazosin for α1 and yohimbine for α2-ADR respectively. IL-23 production from HDM-stimulated BMDCs was suppressed by FORM, 195.2 ± 38.6 pg/ml, but was significantly restored
a cell number (x 104 / ml)
** **
HDM/PBS HDM/FORM
20 ** ** 10
** ** **
HDM/FORM
H-E
0 PBS
HDM /FORM
200 150 100 50 0 PBS
HDM specific IgG1 (LU / ml)
f IL-17 (pg / ml)
e ns
300 IL-13 (pg / ml)
IL-4 (pg / ml)
Figure 2 Formoterol-suppressed HDM-induced airway inflammation. (a) Total and differential cell counts in BAL fluids. (n = 6 in each group) (b) Histological examination of airway inflammation. Sections were stained with H&E (upper panels) or PAS (lower panels). Original magnification was × 200. Br indicates bronchus. Concentrations of (c) IL-4, (d) IL-13, (e) IL-5 and (f) IL-17 in the lung tissues were measured by ELISA. (n = 6 in each group) (g) Titers of HDM specific IgG1 in the serum are shown. *p < 0.01, **p < 0.05.
to 301.9 ± 1.8 pg/ml (Figure 5a) when propranolol was added. ICI118,551 also significantly restored IL-23 production to 355.5 ± 29.5 pg/ml, while CGP20712A did not. Propranolol and ICI118,551 restored IL-6 production suppressed by FORM, but CGP20712A did not (Figure 5b). Interestingly, IL-10 production from HDMstimulated DCs enhanced by FORM, 151.3 ± 17.0 pg/ml, was significantly decreased in a β2 ADR pathway dependent manner (Figure 5c).
We used epinephrine, a full agonist for all classes of ADR, to investigate whether the modulation of DC cytokine production is mediated specifically by β2 ADR. The suppression of IL-23 production by epinephrine, 137.4 ± 21.4 pg/ml, was restored, to 182.3 ± 10.7 pg/ml by propranolol, and to 248.0 ± 26.1 pg/ml by ICI118,551. IL-23 production could not be restored by CGP20712A (105.4 ± 11.6 pg/ml), prazosin (121.6 ± 5.5 pg/ml) or yohimbine (124.5 ± 4.5 pg/ml) (Figure 5d). The suppression of IL-6
Figure 3 Formoterol-suppressed accumulation of cytokine producing cells in regional lymph node of the HDM-induced airway inflammation model. Lymphocytes from bronchial lymph nodes were collected, and cultured at 1.0 × 107/ml in complete RPMI 1640 culture medium containing 10% FBS, in the presence of PMA and ionomycin. After 24 hours, concentrations of (a) IL-4, (b) IL-13, (c) IL-5 and (d) IL-17 in the supernatant were measured by ELISA. (n = 6 in each group) *p < 0.01, **p < 0.05.
production by 1 μM epinephrine, 12.3 ± 2.4 ng/ml, was also restored to 20.9 ± 2.3 ng/ml by propranolol, and to 22.6 ± 2.5 ng/ml by ICI118,551. IL-6 production could not be restored by CGP20712A (14.2 ± 1.2 ng/ml), prazosin (13.6 ± 0.7 ng/ml) or yohimbine (13.1 ± 0.6 ng/ml) (Figure 5e). On the contrary, enhanced IL-10 production by epinephrine, 172.0 ± 11.1 pg/ml, was significantly reduced to 92.8 ± 2.7 pg/ml by propranolol and to 86.1 ± 5.9 pg/ml by ICI118,551 (Figure 5f). HDM-induced airway inflammation was attributed to cytokines produced by DCs
To examine whether the effect of FORM on HDMinduced airway inflammation in vivo depends on DCs, we performed adoptive transfer of HDM-pulsed BMDCs to naïve mice. When intranasal administration of HDMpulsed DCs was followed by HDM challenge, the total number of cells (31.2 ± 13.5 × 104/ml), eosinophils (2.3 ±
1.4 × 104/ml) and neutrophils (13.1 ± 6.9 × 104/ml) in BAL fluids was significantly increased compared with mice given sham-pulsed DC and HDM challenge (Figure 6a). BAL cell counts in the latter group were total cells; 12.1 ± 6.3 × 104/ml, eosinophils; 0.4 ± 0.4 × 104/ml, and neutrophils; 3.6 ± 3.4 × 104/ml. When DCs pulsed with HDM in the presence of 100 pM FORM in vitro were administered to mice, the BAL cell numbers were significantly decreased in comparison to HDM group; total cells; 19.0 ± 3.3 × 104/ml (p < 0.05), eosinophils; 0.3 ± 0.3 × 104/ml (p < 0.05), and neutrophils; 5.0 ± 0.9 × 104/ml (p < 0.05), respectively (Figure 6a). Mice given HDM-pulsed DCs and antigen challenge showed lymphocyte responses similar to mice directly sensitized with HDM. The concentration of IL-4, IL-13, IL-5 and IL-17 in lymph node cell culture was 82.1 ± 31.8 pg/ml, 108.9 ± 32.8 pg/ml, 19.3 ± 6.9 pg/ml, and 181.7 ± 79.6 pg/ml, in the HDM-pulsed DC group, and
Table 1 FORM did not have a direct effect on cytokine production from lymphocytes Mice treated with
HDM 10 mg/ml
FORM added in vitro
100pM
IL-4 (pg/ml)
28.7 ± 2.8
27.2 ± 3.0#
IL-13 (pg/ml)
7.0 ± 15.3
72.3 ± 12.5
70.8 ± 12.6#
#There were no significant difference compared with HDM.
Figure 4 Formoterol- and epinephrine-attenuated cytokine production from DCs in a β2 adrenergic receptor and dose dependent manner. BMDCs, 1.0 × 106/ml in complete media, were stimulated by 10 μg HDM in the presence of various concentrations of FORM or epinephrine for 24 hours. Supernatants were collected, and concentrations of (a) IL-23, (b) IL-6 and (c) IL-10 were measured by ELISA. *p < 0.01, **p < 0.05.
35.9 ± 30.3 pg/ml, 63.0 ± 26.2 pg/ml, 13.7 ± 6.2 pg/ml, and 43.1 ± 24.6 pg/ml, in the sham-pulsed DC group, respectively (Figure 6b-e). Significant differences between the two groups were found for levels of IL-4 (p < 0.05), IL-13 (p < 0.05) and IL-17 (p < 0.05). When DCs were pulsed with HDM in the presence of FORM, the
concentration of IL-4, IL-13, IL-5 and IL-17 in lymph node cell culture supernatants decreased to 45.6 ± 21.6 pg/ml, 61.4 ± 24.9 pg/ml, 17.3 ± 5.1 pg/ml, and 76.3 ± 56.2 pg/ml, respectively. The difference between the HDM group and the HDM/FORM group was significant for levels of IL-13 and IL-17 (p < 0.05).
Figure 5 The effect of FORM and epinephrine on DCs was mediated specifically by the β2 adrenergic receptor. BMDCs were cultured with 10 μg HDM and 100 pM FORM. The effect of various ADR antagonists on cytokine production was examined, (a) IL-23, (b) IL-6 and (c) IL-10. BMDCs were cultured with 10 μg HDM and 1 μM epinephrine. The effect of various ADR antagonists on cytokine production was examined, (d) IL-23, (e) IL-6 and (f) IL-10. *p < 0.01, **p < 0.05.
Figure 6 The effect of Formoterol on the DC adoptive transfer model. BMDCs were stimulated with 10 μg/ml HDM in the presence or absence of 100 pM FORM for 24 hours. BMDCs were collected and washed twice with PBS, then 1.0 × 106 BMDCs in 50 μl PBS were administered to naïve BALC/c mice intranasally. Control mice were administrated 1.0 × 106 BMDCs without HDM and FORM stimulation (n = 6 in each group). On day 10, mice were challenged with 25 μg HDM. Twenty four hours later, mice were euthanized and BAL fluid and bronchial lymph nodes (LNs) were collected. (a) Total and differential cell counts in BAL fluids. After harvesting, bronchial lymph node cells were cultured in the presence of PMA and ionomycin. Concentrations of (b) IL-4, (c) IL-13, (d) IL-5 and (e) IL-17 in the supernatant were measured by ELISA. *p < 0.01, **p < 0.05.
Discussion In this study we demonstrated that FORM suppressed both HDM-induced accumulation of inflammatory cells in the airway and goblet cell metaplasia of airway epithelium in mice. These effects were associated with decreased IL-4 and IL-17 in lung homogenate and decreased accumulation of Th2- and Th17-cytokine production in regional lymph nodes. These observations raise the possibility that β2 adrenergic agonists can attenuate response of DCs to HDM and thus lead to modulation of T cell function. DCs contribute to the initial step of an allergic response after environmental exposure, and play a key role as APC in helper T cell responses [11]. DCs induce naïve lymphocytes to differentiate into Th2 or Th17 cells through production of IL-6 and IL-23 [25,26]. Recent evidence has shown that catecholamines can regulate the immune response through DCs. Antigen presentation by Langerhans cells in the skin was suppressed by epinephrine and norepinephrine in a β2 ADR dependent manner [20]. Crosstalk between TLR4 and β2 ADR transduction pathways in DCs was demonstrated in vitro and in vivo [27]. Matsushita and colleagues reported that dopamine D1-like antagonists attenuate the Th17mediated immune response through DCs and airway inflammation [28]. Therefore, we hypothesized that a β2 ADR agonist has inhibitory effects in allergic airway inflammation. We demonstrated that FORM suppressed IL-6 and IL23 production from BMDCs in vitro and that production was restored by treatment of DCs with β2 ADR antagonists. Furthermore, epinephrine, a full agonist for α and β ADRs, also suppressed cytokine production, which was restored by β2 selective ADR antagonists but not by other classes of ADR antagonists. These observations suggest that the effect of FORM and epinephrine on BMDC is specific and mediated by the β2 ADR signaling pathway. The effect of FORM was about 10,000 times stronger than that of epinephrine which may be explained by the nature of FORM as a long acting β2 agonist. FORM initially diffuses into the plasma membrane of cells, and then is slowly released from the cell, where it can come into contact with β2 ADR [29]. Interestingly, IL-10 production from DCs was enhanced by both FORM and epinephrine. IL-10 is known as an inhibitory cytokine in allergic airway inflammation [30]. Enhanced IL-10 production in DCs contributes to selflimiting airway inflammation. Taken together, these data indicate that a β2 ADR agonist can modulate the function of HDM-stimulated BMDC and suppress allergic inflammation. A recent study reported that repeated challenge with methacholine caused bronchoconstriction without additional airway inflammation and airway remodeling in
asthmatic patients [31]. This finding raises a question that FORM suppressed bronchoconstriction and thus inhibits lymphocyte reactions. To address this question, we conducted a BMDC adoptive transfer experiment. The treatment of BMDCs by FORM suppressed airway inflammation and accumulation of Th2/Th17 cytokine producing lymphocytes in regional lymph nodes. These results strongly suggest that β2 ADR stimulation can attenuate inflammatory processes in an HDM-induced airway inflammation model, through modulation of DC function. The effect of ICS on airway inflammation and hyperresponsiveness is well established. Nevertheless, there remain some issues to be solved. Firstly, a number of patients have airway inflammation resistant to ICS. Bronchial asthma is a heterogeneous disease with several proposed clinical phenotypes [32]. Among them, IL-4 and IL-13-mediated severe atopic asthma with elevated serum IgE and periostin can be treated effectively with an anti-IgE monoclonal antibody, omalizumab, or an anti-IL-13 monoclonal antibody, lebrikizumab [33-36]. Severe non-atopic eosinophilic asthma of late onset is often associated with chronic sinusitis and nasal polyps. This disease is resistant to high dose ICS but responsive to systemic corticosteroids and anti-IL-5 therapy [32,37]. Evidence suggests the involvement of the IL-5/IL-33 signaling pathway in the pathogenesis of this phenotype [38,39]. Other asthmatic patients have corticosteroid resistant neutrophil-dominant disease. IL-17 has been shown to be involved in the pathogenesis of neutrophildominant asthma [9,40,41]. Although macrolide antibiotics may be effective in this steroid-resistant condition [42,43], a better solution is required. Our finding that a long acting β2 receptor agonist, FORM, modulates the Th17 response suggests another possible solution. A second issue is that ICS treatment has to be continued in order to maintain a well-controlled state. In most asthmatic patients, ICS strongly suppresses airway inflammation and establishes a symptom free condition. However, ICS cannot modulate the mechanisms underlying the pathogenesis of asthma, such as atopic sensitization. Thus, once ICS is discontinued, airway inflammation gradually recurs. Asthmatic patients frequently ask their physicians how long they should continue ICS treatment once they have become free of symptoms. To best answer this question, treatment that can improve the underlying condition should be established. Immune-modulation therapies, including antigen desensitization, have been applied to asthmatic patients with modest success [44]. In animal models of airway inflammation, autoimmune encephalomyelitis, nephrotoxic serum nephritis, and rheumatoid arthritis, an antagonist to the dopamine receptor has been reported to attenuate DC function and thus the immunological response [28,45-47]. Our findings extend this concept and
indicate for the first time that an LABA can directly suppress the immunological response in vivo. ICS/LABA combination therapy is a widely used and reliable treatment for asthmatic patients [48,49]. However, recent studies have raised concerns about the safety of LABAs in asthma treatment, due to evidence of an increased risk of severe exacerbation of asthma symptoms leading to hospitalization in pediatric and adult patients, as well as some fatalities [50,51]. Accordingly, the U.S. Food and Drug Administration announced in February 2010 that LABAs should not be used alone in patients with asthma, and that they should be used for the shortest duration of time required achieving control of asthma symptoms [52].
Conclusion Our findings suggested that FORM modulates dendritic cell function and attenuates Th2 and Th17 responses induced by HDM. Thus, we propose that the clinical significance of LABAs should be re-investigated taking into account these immune-modulating effects. Abbreviations HDM: House dust mite; Der f: Dermatophagoides farinae; LABA: Long acting beta 2 adrenergic agonist; ADR: Adrenergic receptor; ICS: Inhaled corticosteroid; FORM: Formoterol; BMDC: Bone marrow derived dendritic cell; APC: Antigen presenting cells; BAL: Bronchoalveolar lavage; H&E: Hematoxylin and Eosin; PAS: Periodic acid-Schiff. Competing interests The authors declare that they have no competing interests. Authors' contributions GK, HT and KT carried out the experimental work, the data analysis and drafted the manuscript. KK and HS extracted the HDM antigen and participated in discussion of the experiments and results. SH and SK provided overall leadership to the experimental design, data analysis, and preparation of the manuscript. All authors read and approved the final manuscript. Acknowledgements We thank Dr. Edmund J. Miller (Feinstein Institute for Medical Research, NY, USA) for critical review of this manuscript. We also thank Dr. Shoichiro Ohta (Saga University, Saga, Japan) for technical assistance with this study.
3. 4. 5. 6. 7. 8. 9.
10. 11. 12. 13.
Declaration of funding sources This study was supported by the Young Researcher Supporting Program of Saga University (KT).
Author details 1 Division of Hematology, Respiratory Medicine and Oncology, Department of Internal Medicine, Faculty of Medicine, Saga University, 5-1-1 Nabeshima, Saga 849-8501, Japan. 2Institute of Tokyo Environmental Allergy, 1-2-5, Yushima, Bunkyo-ku, Tokyo 113-0034, Japan.
Received: 29 April 2014 Accepted: 15 September 2014
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49. Sears MR, Ottosson A, Radner F, Suissa S: Long-acting beta-agonists: a review of formoterol safety data from asthma clinical trials. Eur Respir J 2009, 33:21–32. 50. de Vries F, Setakis E, Zhang B, van Staa TP: Long-acting β2-agonists in adult asthma and the pattern of risk of death and severe asthma outcomes: a study using the GPRD. Eur Respir J 2010, 36:494–502. 51. Wijesinghe M, Weatherall M, Perrin K, Harwood M, Beasley R: Risk of mortality associated with formoterol: a systematic review and meta-analysis. Eur Respir J 2009, 34:803–811. 52. FDA Drug Safety Communication: New safety requirements for longacting inhaled asthma medications called Long-Acting Beta-Agonists (LABAs). In Drug Safety and Availability, Postmarket Drug Safety Information for Patients and Providers. Rockville, MD: US Food and Drug Administration; Available at http://www.fda.gov/Safety/MedWatch/SafetyInformation/ SafetyAlertsforHumanMedicalProducts/ucm201003.htm. Accessed on October 30, 2014. doi:10.1186/s12865-014-0039-y Cite this article as: Kato et al.: β2 adrenergic agonist attenuates house dust mite-induced allergic airway inflammation through dendritic cells. BMC Immunology 2014 15:39.
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Long-acting β2 adrenergic agonists (LABAs) are commonly used combined with inhaled corticosteroids (ICS) to treat asthmatic patients. Previous reports...
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Spend up to 3 minutes with the first picture, including names under each face.
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Symmetric polynomial
From Encyclopedia of Mathematics
A polynomial $f$ with coefficients in a field or a commutative associative ring $K$ with a unit, which is a symmetric function in its variables, that is, is invariant under all permutations of the variables:
\[ \label{symm} f(x_1,\ldots,x_n) = f(\pi(x_1),\ldots,\pi(x_n)). \]
The symmetric polynomials form the algebra $S(x_1,\ldots,x_n)$ over $K$.
The most important examples of symmetric polynomials are the elementary symmetric polynomials
\[ s_k(x_1,\ldots,x_n) = \sum_{1 \leq i_1 < \ldots < i_k \leq n} x_{i_1} \ldots x_{i_k} \]
and the power sums
\[ p_k(x_1,\ldots,x_n) = x_1^k + \ldots + x_n^k. \]
The latter can be expressed in terms of elementary symmetric polynomials by recurrence formulas, called Newton's formulas:
\[ \begin{aligned} p_k - p_{k-1} s_1 + p_{k-2} s_2 + \ldots + (-1)^{k-1} p_1 s_{k-1}+ (-1)^{k} k s_{k} &= 0 \quad &\text{if }1 \leq k \leq n, \\ p_k - p_{k-1} s_1 + p_{k-2} s_2 + \ldots + (-1)^{n-1} p_{k-n+1} s_{n-1}+ (-1)^{n} p_{k-n} s_{n} &= 0 \quad &\text{if }k > n. \end{aligned} \]
For the elementary symmetric polynomials $s_1,\ldots,s_k$ ($1 \leq k \leq n$) of the roots of an arbitrary polynomial in one variable with leading coefficient 1, $x^n+\alpha_1 x^{n-1}+ \ldots + \alpha_n$, one has $\alpha_k=(-1)^k s_k$ (see Viète theorem).
The fundamental theorem on symmetric polynomials: Every symmetric polynomial is a polynomial in the elementary symmetric polynomials, and this representation is unique. In other words, the elementary symmetric polynomials are a set of free generators for the algebra $S(x_1,\ldots,x_n)$. If the field has characteristic 0, then the polynomials $p_1,\ldots,p_n$ also form a set of free generators of this algebra.
A skew-symmetric, or alternating, polynomial is a polynomial $f(x_1,\ldots,x_n)$ satisfying the relation \ref{symm} if $\pi$ is even and the relation
\[ f(x_1,\ldots,x_n) = -f(\pi(x_1),\ldots,\pi(x_n)) \]
if $\pi$ is odd. Any skew-symmetric polynomial can be written [Pr, Thm. 3.1.2] in the form $\Delta_n g$, where $g$ is a symmetric polynomial and
\[ \Delta_n = \prod_{i<j} (x_i-x_j). \]
This representation is not unique, in view of the relation $\Delta_n^2=\operatorname{Dis}(s_1,\ldots,s_n)$.
[Ku] A.G. Kurosh, "Higher algebra", MIR (1972) (Translated from Russian)
[Ko] A.I. Kostrikin, "Introduction to algebra", Springer (1982) (Translated from Russian)
[MP] A.P. Mishina, I.V. Proskuryakov, "Higher algebra. Linear algebra, polynomials, general algebra", Pergamon (1965) (Translated from Russian)
[Pr] V. V. Prasolov, "Polynomials", vol. 11 of "Algorithms and Computation in Mathematics", Springer (2004).
Another important set of symmetric polynomials, which appear in the representations of the symmetric group, are the Schur polynomials ($S$-functions) $S_{\{\lambda\}}$. These are defined for any partition $\{\lambda_1,\ldots,\lambda_p\}=\lambda$, and include as special cases the above functions, e.g. $S_{\{1,\ldots,1\}}=s_k$, $S_{\{ k \}}=p_k$ (see, e.g., [Li, Chapt. VI]).
In general, the discriminant of the polynomial $a_0 x^n + \ldots + a_n $ with roots $x_1,\ldots,x_n$ is defined as $D=a_0^{2n-2} \prod_{1 \leq i < j \leq n} (x_i-x_j)^2$, and satisfies
\[ D = a_0^{2n-2} \begin{vmatrix} p_0 & \ldots & p_{n-1} \\ p_1 &\ldots & p_n \\ \ldots & \ldots & \ldots \\ p_{n-1} & \ldots & p_{2n-2} \end{vmatrix}, \]
with $p_0(x_1,\ldots,x_n)=n$.
See Discriminant.
Let $A_n \subset S_n$ be the alternating group, consisting of the even permutations. The ring of polynomials $k[x_1,\ldots,x_n]^{A_n}$ of polynomials over a field $k$ obviously contains the elementary symmetric functions $s_1,\ldots,s_n$ and $\Delta_n=\prod_{i<j} (x_i-x_j)$. If $k$ is not of characteristic $2$, the ring of polynomials is generated by $s_1,\ldots,s_n$ and $\Delta$, and the ideal of relations is generated by $\Delta_n^2=\operatorname{Dis}(s_1,\ldots,s_n)$. The condition $\operatorname{char} k \neq 2$ is also necessary for the statement that every skew-symmetric polynomial is of the form $\Delta_n g$ with $g$ symmetric. More precisely, what is needed for this is that $2u=0$ implies $u=0$ for $u \in k$.
[Ja] N. Jacobson, "Basic algebra" , 1, Freeman (1974)
[Ku2] A.G. Kurosh, "An introduction to algebra" , MIR (1971) (Translated from Russian)
[vdW] B.L. van der Waerden, "Algebra" , 1, Springer (1967) (Translated from German)
[Li] D.E. Littlewood, "The theory of group characters and matrix representations of groups" , Clarendon Press (1950)
[Po] V. Poénaru, "Singularités $\mathcal{C}^\infty$ en présence de symmétrie" , Springer (1976), pp. 14ff
[Co] P.M. Cohn, "Algebra" , 1, Wiley (1982) pp. 181
How to Cite This Entry:
Symmetric polynomial. Encyclopedia of Mathematics. URL: http://encyclopediaofmath.org/index.php?title=Symmetric_polynomial&oldid=39117
This article was adapted from an original article by O.A. Ivanova (originator), which appeared in Encyclopedia of Mathematics - ISBN 1402006098. See original article
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'Tenet' to open globally on Aug 26, India release date undecided
https://latestnews.fresherslive.com/articles/tenet-to-open-globally-on-aug-26-india-release-date-undecided-135163 2020-07-28 10:33:06 GMT
Los Angeles, July 28 (IANS) An India release date for the Christopher Nolan-directed Tenet is still undecided, although the film has locked August 26 for release across 70 countries before opening in select cities in the US on September 3.
The makers don't have plans to release "Tenet" in China yet.
Right now, Warner Bros. studio have announced that the film will launch across theatres in 70 territories including Australia, Canada, France, Germany, Italy, Japan, Korea, Russia and the UK, confirms a report in variety.com.
India apart, release schedules for the film have not been announced in Argentina, Bolivia, Brazil, Chile, China, Colombia, Costa Rica, El Salvador, Guatemala, Honduras, India, Mexico, Nicaragua, Panama, Peru, Philippines, Puerto Rico, South Africa, Uruguay, and Venezuela.
Last week, the studio shared that "Tenet" would not have a traditional global day-and-date release.
"Tenet", which stars Robert Pattinson and John David Washington, has been described as "an action epic evolving from the world of international espionage". The second trailer of the film came with hints of 'inversion' versus time travel as a part of survival.
The latest trailer of the action thriller gives a glimpse into the mission that the protagonist secret agents, essayed by Pattinson and Washington, embark on, in a time-bending mission to prevent World War III.
The support cast includes Elizabeth Debicki, Dimple Kapadia, Kenneth Branagh, Michael Caine, Dimple Kapadia, Aaron Taylor-Johnson and Clemence Poesy. The film has been shot across seven countries -- India, the US, the UK, Denmark, Estonia, Italy, and Norway.


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Is Hispanic media ownership relevant?
HispanicBusiness.com, News Report, Richard Kaplan
There was a time in the 20th century when media ownership was a priority among minority entrepreneurs. In the Hispanic market the attraction mainly focused on Spanish-language electronic media, particularly radio, and some of the early pioneers of Spanish-language media in the U.S. are still active in today's media markets.
With market activity now expanding to the Web, online media has become the new frontier for pursuing Hispanic media ownership. Minority media ownership remains nonetheless almost as inaccessible as it was during the l970s and '80s.
On the contrary, in recent years, ownership consolidation in the industry has increased. In the 21st century the Federal Communications Commission, which once was at the forefront of advocacy for minority media ownership, has not been supportive. Another complication is the attraction shown by foreign investors and media operators for the U.S. Hispanic consumer market.
Media companies from Latin America and Spain have demonstrated a keen awareness of the growth and potential of the U.S. Hispanic consumer market, especially the Spanish-speaking part of it. All the same, few U.S. Hispanic media entrepreneurs have subscribed to positions and public views shared by proponents of media minority-ownership in the 1960s, '70s and '80s. Virtually no Hispanic leaders speak on behalf of Hispanic media ownership. Media ownership was perhaps the most elusive goal for all minority groups in the 20th century.
The Strengths Of Hispanic Ownership
Amador Bustos, a leading player in the arena of popular Hispanic radio, said Hispanic ownership helps open doors when trying to successfully reach an audience.
His company, Bustos Media, owns more than 30 radio stations strategically placed in many of the nation's leading Hispanic markets.
"It is important to have Latinos in the broadcasting game because the Hispanic owners will undoubtedly have a greater sensibility to the idiosyncrasies of the various Spanish-speaking groups," said Mr. Bustos, whose company has 60 employees and reported $12.9 million in 2007 revenue. "On the programming front, their understanding of the language, culture, and regional politics will contribute to shape the breadth and depth of the news and information coverage. On the employment front, historically Latino owners have been more prone to hire and promote other Latinos."
Hispanic entrepreneurs, Mr. Bustos recalls, were once at the forefront of Spanish-language media. It was their commitment to the community, as well as their capital and cultural knowledge, that drove development.
"Local promoters or entrepreneurs started buying blocks of time in other people's radio or TV stations," he said. "By the early 1970s, Spanish-language programming began to occupy 100 percent of the programming time and Latinos started to own many of those stations around the country."
Entry into the media market was facilitated by the relatively low cost of ownership and regulations limiting the number of stations any one firm could own. Starting in the 1990s, however, consolidation began.
Mr. Bustos explained, "Companies were allowed to own up to eight stations in any one market. We saw a rapid decrease in Hispanic ownership because many of the individual operators sold their stations at a premium (for the time) to the consolidators."
The dwindling number of Hispanic-owned companies forced a seismic shift in the landscape and has allowed entrepreneurs who remained in the market to use Hispanic ownership to their advantage.
Johnny Yataco traces out a similar pattern of consolidation in the print media. In 1994, Mr. Yataco founded and owns the Washington Hispanic, which now has a circulation in excess of 100,000 in the Washington, D.C. area. In the current downturn, his daily paper is doing fine, buoyed perhaps by the continued growth and underlying strength of the country's largest minority.
Currently, says Mr. Yataco, major media corporations are accumulating Hispanic newspapers, but those "conglomerates" consider their audience quite differently than a family-owned, Hispanic firm. When a chain acquires a Hispanic-owned publication, Mr. Yataco said, "the first thing they do is ... start cutting personnel, and when things don't go well, they just cut and cut and cut." Revenue, he said, is the "major driving force."
Of course, revenue is important for the Washington Hispanic and other Hispanic-owned media, Mr. Yataco agrees, but it's not the only concern. Small, local Hispanic papers "know their community," he explained. "We live here. When a newspaper is owned by a big chain, I think they lose touch with the community."
Carmen DiRienzo, president and CEO of the new television network V-me, also insists that Hispanic ownership is crucial for reaching the community.
Founded just 18 months ago, V-me partners with the Public Broadcasting Corporation to reach Hispanic viewers across the United States. The company is partially Hispanic-owned. V-Me is owned by WNET, the New York City PBS member station, and private investors led by the Hispanic-owned Baeza Group. The company has 30 full-time employees but declines to release its annual revenues.
Ms. DiRienzo said her company is "rooted, very rooted in the local Hispanic communities."
Feeding those roots, says Ms. DiRienzo, is partial Hispanic ownership with Mario Baeza serving as V-me's executive chairman, but she also points to the staff and its ties to the community.
"When the people designing the programming are very heavily Latino, as in our case," she asserted, "what they bring to the content is their sensibility as Latino Americans and their understandings of the viewers and the viewers' aspirations."
Capital Difficulties
But it's not always that simple. The idealism of many Hispanic entrepreneurs takes a backseat to the cold realities of the business climate. Competition over advertising dollars makes it tougher for companies to expand, regardless of who owns the company.
A major roadblock for Hispanic-owned media companies continues to be finding financing and advertising dollars, said Maggie Rivas-Rodriguez, a professor in the journalism department at the University of Texas at Austin. "Often in the Latino community, we just don't have the money to put together a newspaper or magazine without outside funding," explained Ms. Rivas-Rodriguez, who formerly reported for the Boston Globe and the Dallas Morning News. "It is a very competitive business right now."
Mr. Bustos agrees. The two biggest barriers to creating new Hispanic ownership of media outlets in the radio industry, he explained, are "access to substantial amounts of capital at a decent interest" and, second, "the scarcity of good signals in populated urban centers."
Future Growth
One Hispanic-owned firm that continues to maintain a strong presence in the Hispanic marketplace is Spanish Broadcasting System (SBS), which owns 20 radio stations in the United States and Puerto Rico and pulled in $179.5 million in gross revenues for 2007.
For Frank Flores, vice-president and market manager for SBS – New York, Hispanic ownership is a key ingredient in the company's success. At the beginning of his career, 28 years ago, he worked for a non-Hispanic station that served the Hispanic market in New York City. Mr. Flores says much of his time was spent in explaining the subtleties of Hispanic culture to the owners, helping to guide them in their programming choices.
At SBS, Mr. Flores says he has no such problems. Comparing Hispanic-owned media to non-Hispanic, he declared, "I've seen the difference between the two, and the difference is stark." Now at SBS, he explained, "We are very much in tune with what our community is all about. ... and I think the community understands it, the community feels it. They know that the radio station is owned and operated by a Hispanic. So there is a certain amount of pride there. And they also know that it's good that these people are in charge because they are going to do the right things for us."
Under the leadership of CEO and President Raul Alarcon Jr., Mr. Flores says SBS has built a "mini Hispanic-owned media company and empire." Despite the current gloomy economic conditions, SBS is well-situated in key Hispanic urban markets and primed for growth. Indeed, once the markets recover and the Hispanic marketplace "fully emerges as the monster that we all know it will become," Mr. Flores is sure SBS will be there to take full advantage of its Hispanic edge.
Labels: Latino Media Owernship


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Harry Andrew Blackmun, 1908-1999. Associate Justice, Supreme Court of the United States, 1970-1994. Mint condition 6" x 9" photograph signed, Harry A. Blackmun, and dated in his hand, February 1983.
This is a very nice printed photograph on bookweight paper, typical of the photographs that Supreme Court justices have sent in response to autograph requests. Blackmun has signed it with a strong blue-black fountain pen signature.
Click here to see other Supreme Court autographs that we are currently offering.


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Tim Bavington
Matchbox, 2015-2017
Painted Steel, 180 x 120 x 400 inches
W Dallas in Victory Park, near Downtown, Uptown, Turtle Creek
Louie, Louie, 2013 / Public Art Installation unveiled at Edith Green-Wendell Wyatt GSA building, Portland, OR
KISS, 2014 / synthetic polymer on canvas / 64 x 64 inches
Heart Above Fifth, 2014 / synthetic polymer on canvas / 60 x 60 inches
Pipe Dream (Fanfare for the Common Man), 2012
Enamel paint on steel, stainless steel, (128 pipes) / 27'- 5" x 86' - 8" x 17'- 1"
Smith Center for the Performing Arts, Las Vegas, NV
Judy Is A Punk, 2009 / Synthetic polymer on canvas / 64 x 96 inches / Collection of the Orange County Museum of Art
She is Love, 2011, Synthetic polymer on canvas / 72 x 72 inches / Collection of the McNay Art Museum
Fanfare (for the Common Man), 2012 / synthetic polymer on canvas
Collection The Smith Center for the Performing Arts, Las Vegas, NV
Sex (Physical), 2005 / Acrylic on canvas / 72 x 161 inches / Permanent
Collection The Museum Of Modern Art
Buddy Holly (Rave On), 2007 / synthetic polymer on canvas over panel / 32 x 32 inches / Collection of Perez Art Museum, Miami
Step (in) Out, 2007 / Synthetic polymer on canvas
96 x 288 inches (244 x 237 cms)
Shown as Installed in Las Vegas Diaspora at Las Vegas Art Museum 2007
Collection Mondstudio (Hamburg, Germany)
Surprise, Surprise, 2003 / diptych, acrylic on canvas / 64 x 128 inches / Permanent Collection The Albright-Knox Art Museum
1984, 2003 / acrylic on canvas / 18 x 24 inches / Permanent Collection The Museum of Contemporary Art, San Diego
Cannonball, 2010 / synthetic polymer and ink on paper / 33 x 33 inches
collection of Museum of Fine Arts Houston
Voodoo Child (Slight Return)/solo/#1, 2001 / Acrylic on canvas / 54 x 72 inches
collection of the Portland Art Museum
Full Fathom Five (Elephant Stone), 2004 / five panels, acrylic on canvas / 120 x 96"
collection of The Steve Wynn Collection
Roll With It, 2004 / acrylic on canvas / 96 x 120 inches / Permanent Collection The Museum of Contemporary Art, San Diego
Columbia, 2008 / 48 x 576 inches (4 x 48 feet)
synthetic polymer on canvas over beveled panels (18 panels)
private collection, Los Angeles
Columbia, 2008
Configuration B (2 panels high, 9 panels across)
Configuration C (3 panels high, 6 panels across)
Witchcraft, 2010 / synthetic polymer on canvas / 60 x 60 inches
Falling Down, 2009 / synthetic polymer on canvas / 60 x 48 inches
Apple Tree, 2007 / synthetic polymer on canvas / 64 x 64 inches
Jump, 2006 / synthetic polymer on canvas / 89 x 63 inches
Elephant Stone/ Full Five (study #1), 2005 / acrylic on canvas on panel / 60 x 48 inches
collection of The Las Vegas Art Museum
Music is the genesis of Tim Bavington's paintings. Through synthetic polymer paint, Bavington acts as a translator between the aural and the visual as he transforms guitar solos, melodies and bass lines into vertical bands of color. Tracks from bands such as The Beatles, The Jam, Oasis, and The Rolling Stones become vibrant bands of color, and bridge compositional concepts between seemingly unlike disciplines. Although Bavington has a method that designates sound to color and composition, the paintings are not literal translations; they remain open to intuition and decision-making, allowing for a distinct artistic presence.
Tim Bavington (b. 1966, England) received his BFA from the Art Center (CA) before making the permanent move to Las Vegas, where he completed his MFA at the University of Nevada, Las Vegas (NV). His work is included in the public collections of Fredrick R. Weisman Collection (CA), Crocker Art Museum (CA), Honolulu Art Museum (HI), Albright-Knox Art Gallery (NY), Creative Artists Agency (CA), Joslyn Art Museum (NE), Museum of Contemporary Art, San Diego (CA), Portland Art Museum (OR), United Talent Agency (CA), Vivendi Universal (CA), Palm Springs Art Museum (CA), Denver Art Museum (CO), The Museum of Modern Art (NY), Nora Eccles Harrison Museum of Art, Utah State University (UT) and the McNay Art Museum (TX). He has exhibited at LeeAhn Gallery (Daegu), Jack Shainman Gallery (NY), Galerie Jean-Luc & Takako Richard (Paris), Space Gallery (London), Museum of Fine Arts (MA), Laguna Art Museum (CA), Museo de Arte Contemporaneo de Buenos Aires, and the Texas Fine Arts Center (TX) among others.
For a full biography and curriculum vitae, please click the PDF download link below.
Stroll On July 23 – August 29, 2015
Heart Above Head January 7 – February 18, 2012
"Decade" April 24 – May 29, 2010
PULSE Contemporary Art Fair: New York
A Solo Booth by Kim Dorland March 4 – 7, 2010
There We Were... Now Here We Are February 16 – March 29, 2008
SUMMER PLEASURES
Bavington, Cerillo, Coulis, Hebert, McGrady, Morrison, Otis, Rowland, Ryan, Schmidberger, Sutherland, Wolberger July 9 – August 20, 2005
Bavington, Fontenot, Schmidberger, Struth, Tillmans, Reafsnyder, Warhol February 19 – March 26, 2005
Andersson, Bavington, Bernhardt, Brown, Cavanaugh, Cunningham, Johnson, Oshiro, Stables, Tucke November 6 – December 18, 2004
Tim Bavington, Alex Blau, Carole Caroompas, Todd Hebert, Ken Kelly, Russ Meyer, Richard Misrach, John Pomara, Mike Reafsnyder, Ed Ruscha, Sush Machida Gaikotsu February 16 – March 30, 2002
New Paintings June 3 – July 8, 2000
CODAmagazine
Transformative Walls II
Tim Bavington's power rock goes acoustic at Mark Moore Gallery
Vegas Seven
UNLV Gets A Bavington
UNLV News Center
UNLV Department of Art Welcomes Tim Bavington to Faculty
AZ Redbook
Tim Bavington Exhibition
The Kingsmen Infamously Innocent 'Louie, Louie'
Back in Front of the Feds at Downtown Federal Building
Merrily Kerr Art Tours
Tim Bavington at Jack Shainman Galler
The Louie Report
LOUIE LOUIE as an art installation in Federal building
Edith Green-Wendell Wyatt federal building
Art in Architecture Program
Is Tim Bavington the Ed Ruscha of Las Vegas? (VIDEO)
Las Vegas Weekly
Best Public Art: "Pipe Dream"
UT San Diego
MCASD auction offers big names, unusual opportunity
Vegas Magazine
Places, Please
Smith Center Symphony Park spires arising
Must See Paintings Shows: January
ARTLOG
Must See Across the USA
New Work From Tim Bavington
Vegas Rated
PULSE: Color Code
Q Vegas Magazine
LA Canvas
Mark Moore Gallery: The Kids Are Alright
ArtLTD
Artist Profile: Tim Bavington
Top Summer Shows You Can Still Catch
Tim Bavington Mark Moore
Art Show: Tim Bavington
ARTnewsletter
Tim Bavington's Rock-Themed Art a Hit With U.S. Collectors
Tim Bavington : Decade
Mark Moore Gallery Statements II
Slower, Savory, Sensations
Sign On San Diego
Intervals is a Small, Solid Showcase
Daily DuJour
Seen: Tim Bavington @ Mark Moore
Society: Fresh Stripes
A Galloping Pulse
Tim Bavington 'Up in Suze's Room'
Sin City Slicker
Artforum.com
Las Vegas Diaspora Review
Art+Auction
David Pagel


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A comprehensive account of ideology and its role in the foreign policy of the United States of America, this book investigates the way United States foreign policy has been understood, debated and explained in the period since the US emerged as a global force, on its way to becoming the world power.
Starting from the premise that ideologies facilitate understanding by providing explanatory patterns or frameworks from which meaning can be derived, the authors study the relationship between ideology and foreign policy, demonstrating the important role ideas have played in US foreign policy. Drawing on a range of US administrations, they consider key speeches and doctrines, as well as private conversations, and compare rhetoric to actions in order to demonstrate how particular sets of ideas – that is, ideologies – from anti-colonialism and anti-communism to neo-conservatism mattered during specific presidencies and how US foreign policy was projected, explained and sustained from one administration to another.
Bringing a neglected dimension into the study of US foreign policy, this book will be of great interest to students and researchers of US foreign policy, ideology and politics.
Associate Professor Brendon O'Connor
Postgraduate Coordinator and Associate Professor in American Politics, United States Studies Centre (jointly appointed with the Faculty of Arts and Social Sciences, University of Sydney)
Brendon O'Connor is jointly appointed between the US Studies Centre and the Faculty of Arts and Social Sciences at the University of Sydney as an Associate Professor in American Politics. He is the editor of seven books on anti-Americanism and has also published articles and books on American welfare policy, presidential politics, US foreign policy and Australian-American relations.
The Foreign Policy and Defence Program receives funding support from the following partners
The 46th | One year on, what's changed?
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Vibration analysis is a crucial process in ship design to guarantee crew's comfortability and to save operating costs by predicting problematical resonance in advance. This study focuses on idealizing fluid mass in tanks by positioning point mass element and quad elements inside the tanks. Also, the added mass effect induced sea water surrounding a ship was included in the present study. The natural frequency obtained from free and forced ship vibration analysis were compared and assessed in the manner of ISO regulation. Finally, it was concluded that the quad element was more adequate to idealize fluid entities in tanks since it was difficult in arranging point mass elements at each grid points properly.


Personalised Candles and Gifts - topical articles, innovations and developments.
We have a wonderful new range of candles for those of you requiring Orthodox celebration candle. Since receiving numerous enquiries regarding the availability of Lambathes, we have decided to add them to our range! The candles are 74cm long and 3 cm wide. They are decorated with traditional soft tulle. The tulle is available in white, blue and pink. Our sample candles have quite simple tulle skirts, however we can make them with a fuller skirt if ordered as such.
We have a vast range of ribbon colours and styles to choose from. You can order the existing candle styles as they appear, or you can substitute different ribbons that can be seen on any of our other candles. The Candles also have various embellishments available, again these can be substituted as required.
Please feel free to contact us for further information, or if there are any other variations you would like.
Our Baptism and Wedding Lambathes can be picked up from Mont Albert in Melbourne. Alternatively we can send the candles to you. We take great care with the packaging of your candles, and due to their size, the delivery charges are a little higher than our other smaller candles.
Please try to order early to avoid disappointment. We look forward to helping you with a special candle for your occasion.
Our much anticipated Menu Candles have arrived! These candles are completely unique, and create a wonderful talking point as a table centrepiece at weddings, corporate events and in restaurants. The Menu Centrepieces are printed on all four sides, so regardless of where a guest is sitting, they can see what is on the menu. There are many styles to choose from, or we can create something completely new for you. Why pay for printed menu's, as well as table centrepieces? Combine the two and make your event an individual and memorable one. We can incorporate any details you would like - bride and groom names, menu options, corporate logo's, business details - anything! They are beautiful looking, functional, individual, and completely fabulous!


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So, I hear trans people recently invented this whole cis/trans thing…
August 12, 2013 · Cristan Williams
By Cristan Williams
@cristanwilliams
Using the cis- and trans- taxonomy to reference gender behavior was used as early as 1914. The transgender community didn't invent its use, nor is its current use inconsistent with its use in 1914. When discussing gender, cis simply means same and trans simply means to cross. Whether it was 1914 or 2014, when someone uses cis regarding gender, it is simply a recognition that one is not trans. Likewise, whether it was 1914 or 2014, when someone uses trans regarding gender, it is simply a recognition that one is not cis.
From the Transgender Archive, Houston, TX
Some context: The above comes in the context of a sexology book from the beginning of the last century when it was popular to scrutinize (and sometimes overly-so) a great deal of human behavior through a psychosexual lens. Thus, whether one was dressing in a manner consistent with their sex assigned at birth or in a manner inconsistent with their sex assigned at birth, the vestments were viewed as sexual symbols that were distinguished through the cis/trans binary.
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The Chichester Harbour Trust welcomes the announcement by Chichester District Council last week that a five-year land supply for the District has now been secured. We hope this will help protect this vulnerable area from the unprecedented levels of spe
Wednesday, 8 December, 2021
The Chichester Harbour Trust welcomes the announcement by Chichester District Council last week that a five-year land supply for the District has now been secured. We hope this will help protect this vulnerable area from the unprecedented levels of speculative planning applications that we have witnessed in the past year.
We are also pleased to see that the some of the sensitive issues around water quality in the Harbour are being addressed through the new Statement of Common Ground with Southern Water and the Environment Agency, with a new position statement in place for the Thornham waste water treatment works. We are reassured that Macquarie, the new owners of Southern Water, have told us of new immediate improvements to Southern Water plant and equipment, and future expansion plans for water treatment capacity.
Likewise, it is good news that CDC has agreed a five-year funding package for the Strategic Wildlife Corridors project to protect and enhance the crucial links between the coast and South Downs, and is refocusing on brownfield sites.
For the first time, the statement released by CDC last week goes some way to addressing many of the concerns raised by the Chichester Harbour Trust and our partner organisations throughout the Harbour community, and reflects many of the challenges and issues that we have been campaigning on. However, we will be following the progress of the Local Plan to see how these initiatives are executed and translated into action to protect the Harbour.
It is still unclear what level of housing development that the district will need to deliver, and it is becoming increasingly clear to everyone that the 12,500 allocated by Government is completely unsustainable for this heavily-constrained district. It is also vital that the narrow corridor of land between the South Downs National Park and Chichester Harbour AONB is protected. There needs to be a stop to the connection of new developments to the sewage system where there is no capacity.
John Nelson, Chair of the Chichester Harbour Trust, said "We at the Trust, together with our supporters and local communities, will be following closely over the coming period to see that these initiatives translate into a revised Local Plan in July that will reflect the exceptional challenges and needs facing this unique area. We must protect the beauty, biodiversity and water quality of Chichester Harbour and we will be keeping up the pressure to achieve this."
Gillian is working closely with the community, local councils and Government Departments on planning issues.
Below you will find updates on her work and other local planning news.


Hi John – you have been v. kind in turning a post of mine into an article so, hopefully, it is OK if I use this space to draw folks' attention to an interesting wee article on BfS site regarding the future potential for commercial sale of water to the non-Scottish parts of UK to help our neighbours address the real problems over future water supplies which they are facing.
Interestingly, one of the items mentioned in the recent ONS statistics concerning the Natural Capital of Scotland was that 2017 had been a record low year for the abstraction of water for the public supply – partly due to the reduction in leakage. Scottish water report that they are investing £3.5 Billion between 2015 – 2021 in their infrastructure. (Whilst managing to limit the increase in water Charge to 1.6% across all council tax bands). There ain't half a lot to be said for keeping water in public ownership.
This is yet another example of the Scottish focussed SNP Scottish Govt keeping their eye on the ball and fighting off all the multiple (nefarious) plots to privatise Scottish Water – keeping the investment tap flowing and preparing the ground for a future industry of potentially huge significance commercially (and of great value in promoting good social and political relationships with our island neighbours post-Indy).


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Q: achieve a contract vs win a contract I am wondering if my understanding of these two phrases is correct. Could you confirm this?

*

*make a contract = create a contract

*achieve a contract = win a contract

Thank you.

A: For no. 1, more acceptable phrases are:

*

*enter into [a] contract
Example:  We must enter into a contract with XYZ Corporation if we want to generate more sales during the next quarter.

*contract with someone (for something) and contract (with someone) for something to make an agreement with someone to produce or supply something, or to do something. I will have to contract with an expert for that part of the project. We contracted with a local builder for a new kitchen. Did you contract for plumbing work with Eric? http://idioms.thefreedictionary.com/contract
For no. 2, "win [a] contract" is already good or correct. It is more commonly used than 'achieve a contract'.
Example:  I am confident we will win this contract with ABC Company.

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