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Enumeration and phenotypical analysis of distinct dendritic cell subsets in psoriatic arthritis and rheumatoid arthritis
- Sarah L Jongbloed†1,
- M Cristina Lebre†2,
- Alasdair R Fraser1,
- J Alastair Gracie1,
- Roger D Sturrock1,
- Paul P Tak2 and
- Iain B McInnes1Email author
DOI: 10.1186/ar1864
© Jongbloed et al.; licensee BioMed Central Ltd. 2005
Received: 13 June 2005
Accepted: 9 November 2005
Published: 16 December 2005
Dendritic cells (DCs) comprise heterogeneous subsets of professional antigen-presenting cells, linking innate and adaptive immunity. Analysis of DC subsets has been hampered by a lack of specific DC markers and reliable quantitation assays. We characterised the immunophenotype and functional characteristics of psoriatic arthritis (PsA)-derived and rheumatoid arthritis (RA)-derived myeloid DCs (mDCs) and plasmacytoid DCs (pDCs) to evaluate their potential role in arthritis. Circulating peripheral blood (PB) pDC numbers were significantly reduced in PsA patients (P = 0.0098) and RA patients (P = 0.0194), and mDCs were significantly reduced in RA patients (P = 0.0086) compared with healthy controls. The number of circulating mDCs in RA PB was significantly inversely correlated to C-reactive protein (P = 0.021). The phenotype of both DC subsets in PsA PB and RA PB was immature as compared with healthy controls. Moreover, CD62L expression was significantly decreased on both mDCs (PsA, P = 0.0122; RA, P = 0.0371) and pDCs (PsA, P = 0.0373; RA, P = 0.0367) in PB. Both mDCs and pDCs were present in PsA synovial fluid (SF) and RA SF, with the mDC:pDC ratio significantly exceeding that in matched PB (PsA SF, P = 0.0453; RA SF, P = 0.0082). pDCs isolated from RA SF and PsA SF displayed an immature phenotype comparable with PB pDCs. RA and PsA SF mDCs, however, displayed a more mature phenotype (increased expression of CD80, CD83 and CD86) compared with PB mDCs. Functional analysis revealed that both SF DC subsets matured following toll-like receptor stimulation. pDCs from PB and SF produced interferon alpha and tumour necrosis factor alpha on TLR9 stimulation, but only SF pDCs produced IL-10. Similarly, mDCs from PB and SF produced similar tumour necrosis factor alpha levels to TLR2 agonism, whereas SF mDCs produced more IL-10 than PB controls. Circulating DC subset numbers are reduced in RA PB and PsA PB with reduced CD62L expression. Maturation is incomplete in the inflamed synovial compartment. Immature DCs in SF may contribute to the perpetuation of inflammation via sampling of the inflamed synovial environment, and in situ presentation of arthritogenic antigen.
The inflammatory arthritides, including rheumatoid arthritis (RA) and psoriatic arthritis (PsA), comprise autoimmune disorders characterised by chronic joint inflammation, immune cell infiltration to the synovium, fibroblast-like synoviocyte expansion and destruction of cartilage and bone. Extensive in vivo and in vitro studies have identified multiple proinflammatory cytokines and enzymes implicated in the pathogenesis of both of these disorders. Targeting cytokines has proven therapeutically useful, exemplified particularly in tumour necrosis factor (TNF) blockade and more recently in targeting IL-6 and IL-15 [1–4]. Cytokine blockade, however, exhibits variable responses across patient populations – and, importantly, disease activity recurs upon cessation of therapy. A major challenge in therapeutics now is to develop strategies that re-establish immune tolerance such that amelioration of inflammation is accompanied by long-term disease suppression. Early evidence that such responses may be feasible is derived from clinical studies utilising CTLA-4Ig [5] and anti-CD20 [6, 7] in RA, and using co-stimulatory blockade in psoriasis [8–10].
Many data indicate the presence and significance of autoimmune processes in articular inflammation. Recent results in RA patients implicate citrullinated peptides in disease progression and response to TNF blockade [11]. Additional auto-specific antigens include type II collagen [12] and cartilage-derived gp39 [13, 14]. Although few autoimmune targets have been identified in PsA, perhaps reflecting the absence thus far of defined autoantibodies, analysis of PsA synovial and skin T cell subsets clearly indicates oligoclonal responses that may be self-targeted [15, 16]. Critically, in both diseases, upstream immunological processes have been poorly characterised ex vivo, particularly with respect to the site and nature of antigen presentation. Antigen-presenting macrophages and B cells play a potential role in synovial inflammation, especially in mediating cartilage degradation [17, 18]. However, the role played by various subsets of dendritic cells (DCs) is less clear [19]. Although enrichment of DCs in RA synovial tissue and fluid and in seronegative synovial fluid has been reported [20–26], the considerable phenotypic, morphologic and functional variations between DC subsets related to lineage, stage of maturation and tissue localisation remains less well understood. This partly reflects the difficulty in adequately identifying DC subsets in peripheral blood (PB) and tissues where most methodologies rely on complex combinations of surface markers.
Novel markers that resolve these issues, useful in human DC studies, have been recently defined [27]. Five distinct subsets of lineage-negative HLA-DR+ DCs have been classified in humans. Four subsets – CD1b/c+, CD16+, blood dendritic cell antigen (BDCA)-3+ and CD34+ – are myeloid-lineage derived, while the fifth subset – CD123 (IL-3Rα+)/CD303 (BDCA-2)+ – has a lymphoid phenotype and is described as a plasmacytoid DC (pDC) [27, 28]. Comprising 0.5–1.0% of all circulating mononuclear cells, myeloid DCs (mDCs) are characterised as CD1c+/CD11c+/CD45RO+/HLA-DR+/CD123 (IL-3Rα)lo. Capable of IL-12-p70, IL-6, TNF-α and IL-10 production in response to bacterial or CD40L stimulation as well as antigen capture and presentation [29], mDCs require granulocyte–macrophage colony-stimulating factor (GM-CSF) for survival in vitro and can differentiate into interstitial DCs and Langerhans cells in the presence of GM-CSF, IL-4 and tumour growth factor beta [30]. Conversely pDCs, characterised as CD303 (BDCA-2)+/CD304 (BDCA-4)+/CD123 (IL-3Rα)high/CD11c-/HLA-DR+/CD45RA+, comprise less than 0.3% of all circulating mononuclear cells and secrete large amounts of the type I interferons (IFNs) in response to herpes or influenza virus stimulation [31, 32].
It has been suggested that DCs play a role in the initiation and perpetuation of inflammatory arthritis by presentation of arthritogenic antigens to autoreactive T cells [19, 33–35]. This presentation may drive aberrant memory T cell responses, promoting B cell activation and immunoglobulin class switching. DC infiltration into the synovium occurs early in the disease pathology [19, 36, 37]. DCs could represent important cellular targets in inflammatory synovitis, by virtue of their potent antigen presentation potential and their capacity to promote local inflammation via toll-like receptor (TLR) expression [38, 39] and cytokine release [31, 40–43]. Recent advances in identifying DC subsets have improved the resolution of subset heterogeneity. We therefore utilised robust assays to quantify and characterise the distribution and phenotype of mDCs and pDCs in blood from PsA patients and RA patients in comparison with osteoarthritis (OA) patients and healthy donors and synovial fluid (SF) from PsA patients and RA patients. We also investigated the functional capabilities of mDCs and pDCs isolated from SF to mature and release cytokines upon TLR stimulation.
Materials and methods
Patients and controls
Inflammatory arthritis patients fulfilled the American College of Rheumatology (formerly the American Rheumatism Association) criteria for RA [44], or met diagnostic criteria for PsA as previously described [45, 46]. All patients and healthy donors gave informed consent and the study protocol was approved by the Ethical Committee, Glasgow Royal Infirmary. PB was obtained from patients with RA (n = 12), from patients with PsA (n = 13) and from patients with OA (n = 11), and was compared with healthy controls (n = 12). SF was obtained from a subset of these donors (RA, n = 6; PsA, n = 6). All cell analysis was undertaken on freshly isolated cells.
For cytokine investigation, cell-free SF and supernatants from cell culture were stored in the Centre for Rheumatic Disease Biobank at -70°C until analysis. Patients were attending the Centre for Rheumatic Diseases, Glasgow Royal Infirmary. At the time of the study, RA patients were receiving methotrexate (n = 7), sulphasalazine (n = 8) or hydroxychloroquine (n = 4), or a combination of these agents (n = 5). PsA patients were receiving either methotrexate (n = 11) or sulphasalazine (n = 4), or a combination of these agents (n = 2). OA patients did not receive any standard immune modulatory therapy. Patients on oral steroids were excluded from the study.
Enumeration of DC subsets in PB and SF
Circulating DC populations were identified by flow cytometry using the FACScalibur system (Becton Dickinson, San Jose, CA, USA) and using a circulating DC enumeration kit (Miltenyi Biotech, Bergisch Gladbach, Germany) according to the manufacturer's instructions (Blood Dendritic Cell Enumeration Kit; Miltenyi Biotech). Briefly, a white blood cell (WBC) count was calculated from PB and SF samples using a Coulter Counter (Beckman Coulter, Fullarton, CA, USA). Aliquots of whole blood were labelled with a cocktail of antibodies including anti-CD14-phycoerythrin (PE).Cy5 and anti-CD19-PE.Cy5 plus or minus anti-CD1c-PE (mDC marker) and CD303 (BDCA-2)-fluorescein isothiocyanate (FITC) (pDC marker) or mouse IgG2a-PE and mouse IgG1-FITC antibodies. A proprietary dead cell discriminator was also included. After incubation, red cell lysis and washing, cells were fixed and examined using a FACScalibur and were analysed using Cellquest software (both Becton Dickinson). Results are expressed as the percentage of mDCs or pDCs in WBCs or as absolute numbers per millilitre of PB/SF (calculated as [% positive - % negative cells] × WBCs per ml [×106/100]).
Isolation of pDCs and mDCs from PB and SF
Both PB and SF samples were diluted in phosphate-buffered saline and mononuclear cells isolated by density gradient centrifugation over histopaque®-1077 (Sigma-Aldrich, Poole, Dorset, UK) and pDCs and mDCs sequentially purified by magnetic cell sorting (Miltenyi Biotec) using a high gradient Mini-MACS® device. pDCs were purified by positive selection using anti-CD304 (BDCA-4)-conjugated magnetic microbeads (Miltenyi Biotec). B cells were depleted using anti-CD19-conjugated magnetic microbeads (Miltenyi Biotec) prior to mDC purification via incubation with biotin-conjugated anti-CD1c and anti-biotin-conjugated magnetic microbeads (both Miltenyi Biotec). FACScan analysis determined that the isolated cell populations from PB and SF were >95% and >93% pure, respectively (<10% neutrophil contamination).
Isolated DCs were phenotyped using the following monoclonal antibodies: CD1c-FITC (mDCs only), CD303 (BDCA-2)-FITC (pDCs only) and CD123-PE (pDCs only) (all Miltenyi Biotec), CCR5-PE (R&D Systems, Minneapolis, MN, USA) (pDCs only), and CD11c-PE (mDCs only), CD14-PE (mDCs only), CD40-APC, CD62L-FITC, CD80-FITC, CD83-APC, CD86-APC and CCR7-PE (all BD Biosciences Pharmingen, San Diego, CA, USA).
mDC and pDC stimulation
All cells were cultured in RPMI-1640 supplemented with 5% human AB serum, L-glutamine (2 mM), penicillin (100 IU/ml), streptomycin (100 μg/ml) and amphotericin B (1.25 μg/ml) (all Sigma-Aldrich). Isolated mDCs were incubated in triplicate at (1–5) × 105/ml containing 50 ng/ml GM-CSF (StemCell Technologies, Vancouver, BC, Canada) alone, or supplemented with Staphylococcus aureus peptidoglycan (PGN) at 10 μg/ml or CpG oligodeoxynucleotide (ODN) 2216 (ggGGTCAAGCTTGAgggggG) at 3.2 μg/ml (both InVivogen, San Diego, CA, USA). Isolated pDCs were incubated in triplicate at (1–5) × 105/ml containing 20 ng/ml IL-3 (StemCell Technologies) alone or supplemented with CpG ODN 2216 at 3.2 μg/ml or ODN 2216c (control for CpG ODN 2216) (ggGGGAGCATGCTCgggggG) at 3.2 μg/ml (both InVivogen). cultures were centrifuged after 24 hours, supernatants collected and stored at -20°C until analysis, and phenotypical analysis by FACScalibur was performed as stated earlier.
Cytokine analysis
Levels of IFN-α in pDC culture supernatants and SF samples were measured using a human IFN-α ELISA (Bender MedSystems™, San Bruno, CA, USA) according to the manufacturer's instructions. Levels of IL-10 and TNF-α in mDC and pDC culture supernatants were assessed using a Luminex kit (BioSource, Nivelles, Belgium) according to the manufacturer's instructions. Results of all cytokine analysis were normalised to 5 × 104 cells per sample.
Statistical analysis
Data are expressed as the median and interquartile range. Statistical significance was determined using the nonparametric Mann-Whitney U test between disease groups and healthy controls. C-reactive protein (CRP) correlation to PB DC numbers was analysed by Spearman Rank correlation. P < 0.05 was considered significant.
Numbers and proportion of circulating pDCs decreased in PsA BP and RA PB, and mDCs decreased in RA PB
The synovial compartment has been the focus of many previous studies of RA and PsA [16, 47]. We chose to examine both the systemic and local levels of circulating DC subsets in inflammatory arthritis, as changes in DC subpopulations have been identified in other autoimmune diseases, particularly systemic lupus erythematosus [41, 48–50]. PB was obtained from RA patients (n = 12) and PsA patients (n = 13) and was compared with PB from OA patients (n = 11) and healthy controls (n = 12).
Patient data
Peripheral blood study group
Synovial fluid study group
Rheumatoid arthritis
Age [mean ± SD (range)]
58 ± 12 (24–80)
59 ± 15 (33–70)
White blood cells [mean ± SEM]
6.4 × 106 ± 1.2 × 104/ml
C-reactive protein
26 ± 6 (6–100)
22 ± 7 (6–41)
Psoriatic arthritis
Age [mean ± SD (range)]
42 ± 14 (24–81)
41 ± 15 (25–50)
White blood cells [mean ± SEM]
8.0 × 106* ± 4.5 × 105/ml
C-reactive protein
14 ± 4 (6–73)
30 ± 15 (6–73)
Age [mean ± SD (range)]
63 ± 12 (52–82)
White blood cells [mean ± SEM]
6.0 × 106 ± 8.9 × 105/ml
C-reactive protein
10 ± 3 (6–14)
Age [mean ± SD (range)]
44 ± 11
White blood cells [mean ± SEM]
6.4 × 106 ± 4.7 × 105/ml
In contrast, circulating pDCs were significantly decreased in both RA PB and PsA PB compared with healthy controls expressed either as total numbers per millilitre of PB (Figure 1c) (RA, P = 0.0194; PsA, P = 0.0098) or indeed as a percentage of WBCs (Figure 1d) (RA, P = 0.0180; PsA, P = 0.0051). In OA PB, although a trend towards a decrease in pDC numbers per millitre of PB was observed, neither mDC nor pDC numbers were significantly reduced compared with healthy controls whether data were expressed as a percentage of total WBCs or as total cell numbers per millilitre of PB.
Reduced RA PB mDC numbers are inversely correlated to CRP
CD62L is aberrantly expressed on RA and PsA circulating PB DCs
RA SF and PsA SF contain mDCs and pDCs
The aforementioned data strongly suggest that DC subset distribution in inflammatory arthritis is abnormal and commensurate with either enhanced migration to the synovial compartment or reduced release from bone marrow. To investigate the former possibility, we chose to evaluate DC subsets in SF. To this aim, we enumerated mDCs and pDCs in SF and matched PB obtained from six patients with RA and from six patients with PsA.
Absolute number of cells (×104/ml) in rheumatoid arthritis and psoriatic arthritis peripheral blood and matched synovial fluid
White blood cells
Myeloid dendritic cells
Plasmacytoid dendritic cells
Rheumatoid arthritis (n = 6)
Peripheral blood
652 ± 93.7
1.36 ± 0.641
0.582 ± 0.211
Synovial fluid
1020 ± 235
11.6 ± 3.12
3.24 ± 1.71
Psoriatic arthritis (n = 6)
Peripheral blood
969 ± 240
1.39 ± 0.420
0.761 ± 0.220
Synovial fluid
2860 ± 351
37.5 ± 8.72
7.20 ± 2.23
SF mDCs have a semi-mature phenotype but pDCs are immature
The only difference observed was an increase of CD86 expression on PsA SF pDCs compared with PsA PB pDCs, although this was not observed on RA SF pDCs. Since CD62L was significantly reduced, but not absent, on mDCs and pDCs from RA PB and PsA PB, we also evaluated expression on SF-derived cell subsets. CD62L was decreased on mDCs and pDCs from both RA SF and PsA SF DC subsets compared with RA PB and PsA PB.
SF mDCs and pDCs mature and release cytokines upon TLR stimulation
It is now recognised that DCs are activated via TLRs [39]. TLR-induced cytokine production was therefore evaluated in disease DCs compared with healthy PB-derived DCs. We purified mDCs and pDCs as already mentioned and evaluated the addition of the TLR2 agonist S. aureus PGN (for mDCs) or the TLR9 agonist CpG ODN 2216 (for pDCs) over 24 hours. For control purposes, mDCs were also incubated with GM-CSF alone or the irrelevant TLR agonist CpG ODN 2216 (mDCs do not express TLR9), and pDCs were also incubated with IL-3 alone or with control ODN 2216c. The phenotypic changes in DC subsets were measured by fluorescence-activated cell sorting analysis and the cytokine release was measured by multiplex assay or ELISA. Irrelevant TLR agonists did not induce cytokine production in any culture conditions tested, nor did they have any effect on in vitro maturation of DC subsets (data not shown).
Together these data indicate that SF DC subsets retain the capacity to upregulate maturation markers and respond to TLR agonists, and that the latter are necessary to promote optimal maturation and cytokine production.
The relative role of innate and adaptive components of the host immune response to inflammatory synovitis is of considerable current interest. DCs comprise a heterogeneous network of professional antigen-presenting cells, capable not only of presenting antigen and inducing subsequent adaptive immune responses, but also of sensing the inflammatory environment and contributing to the cytokine milieu therein. While implicated in the pathogenesis of RA and PsA [19, 33–37], prior analysis of DC subsets has been hampered by a lack of specific DC markers and reliable quantitation methodologies. The present study has utilised the pDC-specific marker CD303 (BDCA-2) and the mDC marker CD1c within a sensitive assay system to provide enumeration and phenotypic analysis of the DC subsets in PB and SF from PsA patients and RA patients. Thereafter we have utilised novel markers to purify DC subpopulations and perform a functional evaluation of their activation potential ex vivo. Finally we have for the first time attempted a phenotypic description of DC subsets in PsA and compared them with those in RA.
We observed a reduction in circulating PB pDC and PB mDC populations in RA patients, and in pDC populations in PsA patients. That this was not observed in prior investigation probably reflects less sensitive methodologies [52, 53] and the identification of subsets based upon CD123 expression, which is also expressed by basophils [54], haematopoietic progenitor cells [55], endothelial cells [56], monocytes, eosinophils and small subsets of lymphocytes [57]. The observed decrease in DC numbers is not due to steroid therapy, which has been reported to reduce DC numbers [58] and function [59], as patients on corticosteroids were excluded from the study.
Decreased PB DC numbers most probably reflect DC migration from the circulation and accumulation to the inflamed synovial compartment. This is consistent with previous studies [52, 53, 60] and with our own data, indicating comparatively high numbers of mDCs and pDCs in SF effusions from both PsA patients and RA patients. In addition, the SF DC subset expression of CD62L (normally cleaved from the cell surface after leukocyte tethering and rolling across high endothelial venules [61]) was lower in both PsA SF and RA SF compared with the peripheral blood compartment, further indicative of migration.
In preliminary studies, we have utilised these novel markers to identify pDCs in RA, PsA and in OA synovial membrane (SM) itself (see Additional file 1). Future detailed phenotypic analysis of such membrane DC subsets is now necessary, and will offer insight into the migratory pathway and functional activities of distinct DC subsets in chronic synovitis. Finally, the trend towards decreased PB pDC numbers in the OA patients, although not significant, may be indicative of altered DC migration toward the synovial compartment. OA is associated with synovial hypertrophy, hyperplasia, local inflammation and recurrent effusions [62].
Other factors may operate in regulating detectable blood DC numbers, however, particularly within the bone marrow – in which it is increasingly recognised that functional maturation defects may exist for leukocyte lineages [63]. For example, reduced pDC numbers in circulating PB could reflect elevated TNF-α expression [64, 65]: TNF-α is known to inhibit fms-like tyrosine kinase 3-ligand-driven differentiation of pDC from bone marrow progenitors [51, 66]. Future studies will be required to establish the circulating half-life and tissue destination of DC subsets in the context of inflammatory arthropathies, and indeed of the effect of cytokine blockade on such parameters. It should also be noted that reduced circulating DC subsets have been demonstrated in several other inflammatory disorders, including systemic lupus erythematosus [48] and chronic active hepatitis [67], and that regulatory pathways in such diseases may also be informative in elucidating DC function in synovitis.
A further novel observation was the reduced CD62L expression on both DC subsets in PsA PB and RA PB. Reduced CD62L expression on RA PB CD3+ and CD19+ lymphocytes, monocytes and granulocytes [68] has been linked to immunosuppressive therapies including methotrexate [69], and a similar mechanism could explain our observations. However, downregulation of adhesion molecules such as CD62L is necessary for the release of CD34+ progenitors to the PB [70], and it is possible that a CD62Llo PB DC population may indicate altered recirculation or modified release of bone marrow DC precursors.
Purified SF pDCs were recently reported to exhibit a relatively immature phenotype given their inflammatory environment [52, 53]. Similar observations have been made for mDCs [26, 60]. We now confirm these observations in RA and extend the data to include PsA-derived cells, indicating that the inflamed synovial compartment per se can sustain immature DCs capable by inference of antigen sensing, capture and, ultimately, presentation. Upon removal from the SF, both mDCs and pDCs were capable of increased maturation marker expression and, provided with TLR agonist activation, were capable of cytokine release. There does not therefore appear to be an intrinsic functional defect of DCs. Whereas TLR2 or TLR9 stimulation was not sufficient to induce substantial IL-10 release from healthy PB mDCs and pDCs, it was sufficient for IL-10 release from PsA SF and RA SF purified cells.
The functional implications of this observation are unclear and require further examination to include other TLR agonists and DC activation conditions. In particular we now wish to examine the cross-regulation of mDC and pDC subsets in the context of inflammatory synovitis. That said, the technical demands of isolating primary DCs from an inflamed compartment (particularly pDCs) are not insignificant and place limitations on feasible functional analyses. Very few groups have thus far attempted formal functional evaluation of purified DC subsets from any inflamed tissue. Our approach combines a broad but pragmatic approach to start to examine DC function ex vivo. Future technical refinements will be required to perform the desired extensive in vitro analyses of DC function that will more comprehensively address their functional role.
These are the first data to investigate purified DC subsets in PsA patients. Prior studies have identified pDC in cutaneous psoriasis and increased type I IFN expression in psoriatic plaques after application of a TLR agonist [71]. Numerous data indicate a role of T cells in PsA pathogenesis [72]; determining the functional role of both pDCs and mDCs in PsA synovium should therefore be informative. The present study provides the essential pre-requisite for such studies in determining the presence, enumeration and function of each subset in PB and SF.
IFN-α was detected in SF in both RA patients and PsA patients. The role for this cytokine in synovial pathogenesis is indicated by numerous reports linking IFN-α therapy to induction of RA and PsA in patients with no pre-existing clinical arthritis [73–75]. Moreover, IFN-α is sufficient to drive monocyte differentiation to mDCs in systemic lupus erythematosus patients [76]. The significantly increased mDC:pDC ratio identified in SF may indicate in situ differentiation of monocytes shed from the synovial lining layer to mDCs, driven in part by IFN-α in the fluid. It is therefore intriguing to consider a local cytokine-mediated feedback loop whereby pDC IFN-α release promotes local mDC maturation. Consistent with this, we have recently observed that PsA SF is capable of inducing differentiation of mDCs from PB-derived monocytes (unpublished observations).
While only mature DCs are able to induce the activation of T cells and the differentiation of B cells into antibody-producing plasma cells, immature DCs are able to capture antigen at picomolar and nanomolar concentrations [77]. In the steady state, presentation of these self-antigens should sustain tolerance. However, the presentation of these antigens within an inflammatory context, such as the inflamed synovial compartment in susceptible individuals, may lead to chronic inflammation and autoimmune disease. SF apparently contains a pool of immature DC subsets of both mDC and pDC lineage that could facilitate (auto)antigen capture, and thereby the initiation or perpetuation (neoepitopes) of autoimmunity.
In summary, we have performed a comparative evaluation of RA and PsA circulating and SF DC subsets. Our data show that mDC and pDC numbers are significantly decreased in RA PB and that pDCs are significantly decreased in PsA PB, and that both subsets exhibit reduced CD62L expression. These data indicate an altered recirculation or circulating half-life for DC subsets in inflammatory arthritis. Both mDCs and pDCs are present in SF from RA and PsA, with pDCs expressing an immature phenotype whereas mDCs express a semi-mature phenotype. Synovial fluid DCs remain responsive to TLR agonism, exhibiting maturation ex vivo and cytokine release. Future studies are now required to evaluate those factors that prevent local maturation of DCs in synovial fluid and to determine the functional significance of immature DCs maintained in the fluid compartment of the inflamed joint.
blood dendritic cell antigen
cc-chemokine receptor
- CpG:
immunostimulatory bacterial CpG-DNA sequence
C-reactive protein
dendritic cell
enzyme-linked immunosorbent assay
fluorescein isothiocyanate
granulocyte–macrophage colony-stimulating factor
- mDC:
myeloid dendritic cell
peripheral blood
- pDC:
plasmacytoid dendritic cell
- PsA:
psoriatic arthritis
rheumatoid arthritis
synovial fluid
toll-like receptor
tumour necrosis factor
white blood cell.
The authors would like to thank the Arthritis Research Council UK and the Glasgow Royal Infirmary Research Endowment Fund for funding the study, as well as the clinicians and patients of Glasgow Royal Infirmary for supplying clinical samples.
Authors' Affiliations
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This article is published under license to BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


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In the bizarre couple of days immediately following the US election a predictably large amount of codswallop was spouted on social media, and that was...
Music's Super Bowl — the 59th Annual Grammy Awards — will be held on Sunday, February 12th. With highly anticipated performances by Katy...
The way Taylor Swift got to the top was by coming across as incredibly grounded and honest: super-talented but still the girl next door. The reason she lost her way was because she started hanging out with models and film stars and drifting away from her roots.
Despite the headaches of tape in my early years I've come back to it. It took many months of agonising over which cassette deck to buy and whether I'd even enjoy the hobby; after all, together with my wife we've amassed a large collection of vinyl records that offer a warmer, clearer, just plain higher sound quality.
When it comes to climate change, the math and science are clear -- but not to everyone. The arts can be powerful allies in helping us all understand the severity of the challenge and the urgency for action.
As a cultural presence that combined the sacred and profane, romance and cynicism, humanity and hopelessness for over five decades of towering songs, we all have our own Leonard Cohen entry point. Like fellow Canadian Neil Young, Cohen became a patron saint of the 90s alternative nation. There was the tribute album "I'm Your Fan" and placement of "Closing Time and, especially, "The Future" in the film "Natural Born Killers."
The digital era, it was believed, would usher in a utopia for both musicians and the consumer. But in reality, artists - the people who build our nation's cultural foundation and much of the intellectual property we export - now struggle more than ever to earn a living. The creative middle class has virtually ceased to exist.
By Tuomas Eerola
Tear-jerkers such as Adele's Someone Like You frequently top the charts these days, while gloomy classical compositions like Mozart's Requiem...
I wrote the following this morning and now comes word tonight that Leonard Cohen, one of the greatest writers of our time (poet, novelist, songwriter)...
Bob Dylan's recent win of the Nobel Prize in Literature has raised eyebrows and has come with mixed feelings within the literati community. There are persons who see the academy's decision to award Dylan this coveted prize as "misguided and questioned whether songwriting, however brilliant," deserves to be ranked at the same standard as literature.
Before Gord, Mike Downie and Pearl (Chanie Wenjack's sister) got on stage at WE Day, I knew about the conditions of the indigenous communities, but like most Canadians, we weren't taught what a residential school was and why both the truth and reconciliation is so important to not only the indigenous community.
Canadian groups headed to America have two choices: Stump up $2000-$5000 in border fees and union dues and wait weeks for a permit, or go without and risk a two to five year personal ban from the US. Whether it's a one night show played for beer and beds or a full arena tour makes little difference to the costs and paperwork involved.
Why even bother? Why play a game that was designed for you to lose? The industry is completely unaware of the over-qualified and overlooked people of colour that play an important role in it, often claiming that they don't exist.
It comes as little surprise that the likes of Skrillex and Deadmau5 cite the French duo as their greatest influence. Discovery surely stands as one of electronic music's best, most influential records - and Harder Better Faster Stronger the album's most forward-thinking, innovative track.
Beatlemania was an important cultural phenomenon that changed the course of postwar history. Millions of baby boomers across a 15-year age range, across the globe, were smitten by four charismatic lads who, through their music, attitude, wit, and intelligence, excited us, dazzled us.
Regardless of where you stand on the issue, I like the idea that the Nobel committee chose someone without contempt for Israel.


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Bond issues
On 19 November 2010, AccorHotels had announced the launch of a tender offer to repurchase parts of bonds maturing in 2013 (6.5%) and 2014 (7.5%), subject to a maximum aggregate principal amount of Euro 400,000,000 in line with its de-leveraging strategy. With this transaction, AccorHotels reduces its gross debt and optimizes its debt structure.
During the Tender Offer Period, an aggregate principal amount of Euro 283 million was validly tendered by Bond holders and accepted by AccorHotels for repurchase. The amount is split as follows:
- Euro 151m of the Euro 600m 6.5% Notes due May 2013
- Euro 132m of the Euro 600m 7.5% Notes due February 2014
All bonds purchased by AccorHotels have been immediately cancelled and will not be re-issued. The settlement of the Tender Offer was on Wednesday 1 December, 2010.
In 2011, AccorHotels pursued the partial repurchase of its bonds:
- Euro 56m of the Euro 600m 6.5% Notes due May 2013
- Euro 65m of the Euro 600m 7.5% Notes due February 2014
In 2012 and 2013, AccorHotels successfully launched two new bonds, taking advantage of favorable conditions on the credit market. These operations enable AccorHotels to both lengthen the average maturity of its debt and optimize its average cost of funding.
- Euro 700m, 2.875% Notes due June 2017
- Euro 600m, 2.5% Notes due March 2019
In 2014, AccorHotels successfully launched three new bonds, taking advantage of favorable conditions on the credit market. Those issues strengthen AccorHotels' flexibility in deploying its strategy.
- Euro 750m, 2.625% Notes due february 2021
- Euro 900m, 4,125% Notes due june 2020 with the rate reset every 5 years thereafter
- Euro 150m, 1,728%, Notes due february 2021


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True Blood
Mon Oct 7, 10-11.10pm, Fox
It's a sign of how far this show has declined that not even the introduction of the estimable Rutger Hauer (as Jason and Sookie's long-lost grandfather) can revive it for long.
While Eric takes the fight to the Governor after Tara's shooting, Sookie is taken in by yet another handsome stranger and Bill contemplates how to employ his awesome new powers, narratives and chronologies shift so quickly that, in its desperation not to bore us, 'True Blood' merely frustrates and confuses us instead.
No series can pull off this sort of storyline juggling for ever, and 'True Blood' started dropping the balls some years ago. Now, stripped of any narrative tension by its 'anything goes' universe, it's an underwhelming mess.


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Massage Parlors
Kick back, relax, here any topic is fine, well... almost any topic... :-)
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Massage Parlors
During my last visit in January, I noticed a bunch of these places all over town. Are these places to get theraputic massages or are they more like the "asian massages parlors" in the US and Canada. If anyone admits vgisiting ony of these places, please email me with the details. Thanx.
Re:Massage Parlors
I saw a bunch of these on my last visit too! What's happening to good 'ol PV?
Re:Massage Parlors
Venus, Metamorfosis, Body Time, and Body and Sol are all theraputic, not out-call massages.
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Tickets and additional information can be found here. Olken and Loh met as classmates at SUNY Purchase where Stone Cold Fox originated as an acoustic bedroom project. It has since expanded and grown into a solid indie-folk group that "emanates a youthful and energetic sense of comfort through beautiful songs, simple aesthetics, and innovative production." (FIKA Coffee Break). DrawingFind out more »
More information can be found here. Join us in celebrating the release of Steph Barrak's debut album, "Words To Break Your Heart," at UFORGE Gallery in JP. + Live music + Refreshments/snacks + No cover + Surrounded by art! Music Line-up: 8:20 - 8:40 Holden Laurence (http://www.holdenlaurence.com/) 8:45 - 9:05 Eva Walsh (http://www.evawalsh.com/) 9:15 -Find out more »


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This report critiques the handling of domestic policy aimed at
Reducing Emissions from Deforestation and Degradation (REDD) by the Government of Papua New Guinea (PNG) and the way it has engaged with international REDD negotiations since the...
Australia is on the brink of a complete shift in the way that we produce and consume food. Our most important staple crop and major agricultural export – wheat – is under serious threat.
Our oceans are in crisis. Hardly a week goes by
without another major study linking the loss of
marine biodiversity with human activity. Scientists
repeatedly warn that many ocean ecosystems are
fast approaching tipping points whereby they...
How Australian supermarkets stack up on tuna sustainability - July 2010
On 20 April 2010, an explosion engulfed the British Petroleum Deep Horizon exploratory drilling platform, which led to its collapse and sinking. The failure of U.S. energy policy once again was demonstrated in the Gulf of Mexico.
How Australian supermarkets stack up on tuna sustainability. Full report, March 2010.
Ninety percent of genetically engineered (GE) seed is made and owned by one US company called Monsanto, and they don't want us to know when GE is in our food.
The frequency of catastrophic fire danger could increase more than ten-fold in Melbourne, and the number of total fire ban days would triple in Adelaide, Canberra and Sydney by 2050.
Read about it in this report from the Fire Brigades...
A non-invasive biotechnology alternative to genetic engineering
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Einen TinyCore habe ich auch runtergeladen und in die Ordnerstruktur eingebunden unter hardware/arduino/core.
Sorry, there was a change in 1.0.2 that is incompatible with processors that don't have hardware serial support (like the ATtiny). This will be fixed in 1.0.3. See: https://github.com/damellis/attiny/issues/8. For now, you can use 1.0.1 or change:#error TXC0 not definable in HardwareSerial.hto:#warning TXC0 not definable in HardwareSerial.hin HardwareSerial.h.
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These are the Federal 2013 Contact Grips. Super comfy and super grippy. Featuring Federals mini flanges, these grips will not let you down!
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|Shadow's Fund
Always spay or neuter your pets. Visit Shelter Website
|Shadow's Fund is dedicated to the rescue, rehabiIitation and re-homing of seniors, pit buIIs and other high risk dogs in sheIters. Through education and funding programs, we provide the tooIs necessary for the successfuI adoption of these speciaI needs dogs. To bring hope to those who have none.
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|Rescue Me ID: 15-06-15-00006LUKE (male)
About Luke Luke is about 3 years old and one of the most playful, dog social, puppy-like, wiggly wonders to ever come through Shadow's Fund. Once he gets to know you, you're his best friend, ready to hike, swim, play tug, run a few miles or snuggle on the couch. An all-around sweetheart of a dog. But this shy boy needs a loving family, a little patience and some understanding to help him work through his shyness. Unfortunately, Luke was not treated so well in the first part of his life and he's very shy with new people. It takes him a little while to warm up, but once he has, you'll be laughing and singing his praises. Luke's ideal home ... (Read More)would have other playful dogs and active adults. Just give him a chance and he'll steal your heart. For more information please contact Shadow's Fund by email at firstname.lastname@example.com . (Less)
Shadow's Fund
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|Rescue Me ID: 15-06-11-00003MITTENS (female)
About Mittens Mittens is still a little shy, but is coming out of her shell a little more each and every day. A concerned citizen finally caught her after seeing her running around loose for many weeks. She had been abandoned, left to fend for herself, in the middle of winter and eventually found in herself to trust a stranger. She spent a few weeks in a vet office while they looked for her home, but no one came forward. With nowhere for her to go, Shadow's Fund was able to step in and bring her to their sanctuary. And she's doing wonderfully. She's amazing in the house, walks really well on leash and responds to verbal commands right ... (Read More)away. She loves to play with other dogs and pesters them for more when they're no longer interested. She's a silly, little, wiggly girl and her favorite place in on your lap, or snuggled into blankets. It takes her a few minutes to warm up to new people and new dogs, but once she does she's your best friend. She prefers mellow dogs to energetic ones at this point, but is doing well with all energies with a proper introduction. She loves kids and loves giving them kisses on their noses. We don't know how she is with cats, but we imagine she could learn very quickly as she does not have a strong prey drive. You'll be amazed how great she is and how fast she'll win you over. For more information please contact Shadow's Fund by email at firstname.lastname@example.com (Less)
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Santa Barbara County Lompoc, CA 93436 MAP IT!
|Rescue Me ID: 15-05-21-00257FRODO (male)
9 month old Frodo would make a wonderful addition to nearly any family! He would do best with other dogs and/or kids to play with (or both!) but as long as he gets to be part of the family he will be thrilled. He is incredibly sweet, well socialized and playful (but tires quick and is ready for a nap). It has been remarked that he is very calm for a youngster. If you want a great family dog to raise but don't want to do the puppy thing, consider Frodo. Email us at firstname.lastname@example.com to meet him!
Shadow's Fund
Santa Barbara County Lompoc, CA 93436 MAP IT!
|Rescue Me ID: 15-05-05-00015PEANUT (female)
Peanut is a little fireball of energy and cuteness. She is a blank canvass just ready to learn. She was rescued through our Bright Beginnings Pit Bull Puppy Ambassador program. All of her pups have grown and are adopted. Now its mama's turn to find a home that will help her learn all that she needs to know to be solid canine citizen. Email firstname.lastname@example.com if interested
Shadow's Fund
Santa Barbara County Lompoc, CA 93436 MAP IT!
|Rescue Me ID: 15-04-26-00499SHIVA (female)
About Shiva Outgoing and social, Shiva loves to be the center of attention. This wiggly 2 yr old will happily join you for a walk, run, or hike or just be a cuddle companion for movie night at home. She is just happy to be with her favorite person or people. Shiva the Diva is what the volunteers call her and she is just a joy to be around.
Shadow's Fund
Santa Barbara County Lompoc, CA 93436 MAP IT!
|Rescue Me ID: 15-04-25-00501LADY (female)
About Lady Meet Lady. Our grey muzzled friend here was abandoned at the time in her life when she needed her family most - as she enters her golden years. This 10 yr old was picked up off the streets and taken to the local shelter were we found her. That is behind her now and the only thing Lady wants to do is wiggle, bounce, go for walks and enjoy some good ear scratches. She could not be sweeter and she simply brings a smile to your face every time you are with her because she is just full of light and joy. As much as we love her sweet silver face here at the sanctuary, we'd love it more if we knew she were waking up in a home of her own ... (Read More)every morning. Anyone out there have room in their heart and home for Lady? If so, email us at firstname.lastname@example.com. (Less)
Shadow's Fund
Santa Barbara County Lompoc, CA 93436 MAP IT!
|Rescue Me ID: 15-04-17-00015GINGER (female)
About Ginger Ginger is a feisty red head that is playful and loves other dogs. She is incredibly smart, athletic and loves a challenge. She would do well in an active sport like agility where she could show off her physical and mental strengths. She also loves quiet snuggle time. She will need a fairly active family to keep her mentally and physically challenged, and will do best with a doggie companion. Ginger experiences separation anxiety now and will need a patient and loving person to help build her confidence and security. But this petite little sweetheart will be well worth the investment! Contact Shadow's Fund at firstname.lastname@example.com
Shadow's Fund
Santa Barbara County Lompoc, CA 93436 MAP IT!
|Rescue Me ID: 15-04-09-00892Diesel & Shadow (male)
This pair is closely bonded and needs to be adopted together! About Diesel & Shadow Known as the Tater Tots at Shadow's Fund, Diesel and Shadow were found on a rural road after they were abandoned. A passerby found them and took them home. Malnourished, dehydrated and a little scared...and they could not have been any sweeter. The brother and sister pair are short and stocky, sweet and cuddly, playful and fun. Diesel, the male, is about 70 lbs and loves playing fetch. Shadow, the female, is about 60 lbs and wants nothing more than to nap by your side. The pair are good with kids, walk well on leash, and are very affectionate. These pups ... (Read More)have been through a lot and deserve the comfort of a warm bed and the love of a family. For more information please contact Shadow's Fund at (805) 735-3165 or by email at email@example.com . (Less)
Shadow's Fund
Santa Barbara County Lompoc, CA 93436 MAP IT!
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text:
Qualcomm Sampling ARM-Based Server Chip With Businesses
The chip maker demonstrates a 24-core SoC running open-source software and announces partnerships with Xilinx and Mellanox.Almost a year after announcing it was getting into the server chip business, Qualcomm is sampling its ARM-based processor with tier-one data centers. The Oct. 8 announcement came at an event in San Francisco where Qualcomm executives demonstrated its Server Development Platform (SDP) using a pre-production version of a 24-core system-on-a-chip (SoC) that was built using the 64-bit ARMv8-A instruction set. The processor makes Qualcomm the latest vendor to move its ARM-based SoC technology up the ladder from smartphones and tablets and into the data center. Other companies, such as Applied Micro, Cavium, Marvell Technologies, Broadcom and Advanced Micro Devices, either have products on the market or in their roadmaps in hopes of challenging Intel's dominance in the data center with its broad range of x86-based processors. "The release of our evaluation system is a major milestone for Qualcomm Technologies," Anand Chandrasekher, senior vice president said in a statement. "As data centers evolve to support the exponential growth and innovation in data, connectivity and cloud services, Qualcomm Technologies is creating an ecosystem to meet the needs of these next-generation data centers with Qualcomm-based server technologies."
Qualcomm customers "are eager to test and evaluate our Server Development Platform and begin porting their software," Chandrasekher said. "We are incorporating their feedback into our product offering with the goal of ensuring system and software readiness by the time we are in full production."
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text:
Hawkish comments from a member of the Bank of England's Monetary Policy Committee (MPC) coupled with a perceived weakening of the CBI's "the next move should be down" stance on rates re-awakened fears of an interest rate hike following next week's MPC meeting.
After a weak start, the pound gained almost a pfennig against the mark following a speech by Mervyn King, the Bank's chief economist and executive director, at the Building Societies annual conference.
Sterling finished the day at DM2.905, up from 2.898 on Tuesday.
Mr King, a "hawk" who voted for a rate rise at April's MPC meeting, said domestically generated inflation was "significantly higher than RPIX inflation [the measure of inflation targeted by the Government]". Mr King warned: "Inflation will start to rise above the target unless domestically generated inflation declines".
He added: "The earnings figures released earlier this month - which showed that average earnings in the economy grew by 4.9 per cent and in the private sector by no less than 5.6 per cent - were undoubtedly disappointing. To hit the inflation target those rates of earnings growth will have to fall back."
Mr King said that even though the MPC predicted a slowdown in the economy, it might not be sufficient in itself to hold back inflation.
Meanwhile, the Confederation of British Industry (CBI) indicated a slight softening over its stance on interest rates by warning that the country could not afford to trade "short-term gain for long-term pain".
Addressing the organisation's annual dinner in London last night, the CBI president Sir Colin Marshall called on the Government not to ease up in the fight against inflation.
He also gave a rare acknowledgement that the strong pound, while hurting manufacturers, exporters and inward investors, was also good news for importers, retailers and holidaymakers.
Speaking after the Prime Minister, Tony Blair, had addressed the dinner, Sir Colin said the CBI had been encouraged by the way the Government had seen eye to eye on the need for stability, sustainability and economic development.
But he added: "Central to our largely mutual philosophy is the need to combat and control inflation, ahead of almost all other economic considerations. "We simply cannot afford to trade short term gain for long-term pain."
Despite yesterday's developments, most City economists still believe the outcome will be "no change" after next week's two-day MPC meeting, which will start on Wednesday.
- More about:
- Inflation
- Manufacturing
- Mervyn King
- Tourism


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text:
1 Samuel 23New International Version (NIV)
David Saves Keilah
23 When David was told, "Look, the Philistines are fighting against Keilah and are looting the threshing floors," 2 he inquired of the Lord, saying, "Shall I go and attack these Philistines?"
The Lord answered him, "Go, attack the Philistines and save Keilah."
3 But David's men said to him, "Here in Judah we are afraid. How much more, then, if we go to Keilah against the Philistine forces!"
4 Once again David inquired of the Lord, and the Lord answered him, "Go down to Keilah, for I am going to give the Philistines into your hand." 5 So David and his men went to Keilah, fought the Philistines and carried off their livestock. He inflicted heavy losses on the Philistines and saved the people of Keilah. 6 (Now Abiathar son of Ahimelek had brought the ephod down with him when he fled to David at Keilah.)
Saul Pursues David
7 Saul was told that David had gone to Keilah, and he said, "God has delivered him into my hands, for David has imprisoned himself by entering a town with gates and bars." 8 And Saul called up all his forces for battle, to go down to Keilah to besiege David and his men.
9 When David learned that Saul was plotting against him, he said to Abiathar the priest, "Bring the ephod." 10 David said, "Lord, God of Israel, your servant has heard definitely that Saul plans to come to Keilah and destroy the town on account of me. 11 Will the citizens of Keilah surrender me to him? Will Saul come down, as your servant has heard? Lord, God of Israel, tell your servant."
And the Lord said, "He will."
12 Again David asked, "Will the citizens of Keilah surrender me and my men to Saul?"
And the Lord said, "They will."
13 So David and his men, about six hundred in number, left Keilah and kept moving from place to place. When Saul was told that David had escaped from Keilah, he did not go there.
14 David stayed in the wilderness strongholds and in the hills of the Desert of Ziph. Day after day Saul searched for him, but God did not give David into his hands.
15 While David was at Horesh in the Desert of Ziph, he learned that[a] Saul had come out to take his life. 16 And Saul's son Jonathan went to David at Horesh and helped him find strength in God. 17 "Don't be afraid," he said. "My father Saul will not lay a hand on you. You will be king over Israel, and I will be second to you. Even my father Saul knows this." 18 The two of them made a covenant before the Lord. Then Jonathan went home, but David remained at Horesh.
19 The Ziphites went up to Saul at Gibeah and said, "Is not David hiding among us in the strongholds at Horesh, on the hill of Hakilah, south of Jeshimon? 20 Now, Your Majesty, come down whenever it pleases you to do so, and we will be responsible for giving him into your hands."
21 Saul replied, "The Lord bless you for your concern for me. 22 Go and get more information. Find out where David usually goes and who has seen him there. They tell me he is very crafty. 23 Find out about all the hiding places he uses and come back to me with definite information. Then I will go with you; if he is in the area, I will track him down among all the clans of Judah."
24 So they set out and went to Ziph ahead of Saul. Now David and his men were in the Desert of Maon, in the Arabah south of Jeshimon. 25 Saul and his men began the search, and when David was told about it, he went down to the rock and stayed in the Desert of Maon. When Saul heard this, he went into the Desert of Maon in pursuit of David.
26 Saul was going along one side of the mountain, and David and his men were on the other side, hurrying to get away from Saul. As Saul and his forces were closing in on David and his men to capture them, 27 a messenger came to Saul, saying, "Come quickly! The Philistines are raiding the land." 28 Then Saul broke off his pursuit of David and went to meet the Philistines. That is why they call this place Sela Hammahlekoth.[b] 29 And David went up from there and lived in the strongholds of En Gedi.[c]
Cross references:
New International Version (NIV)
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Recognition For Work With Vulnerable Customers
Western Power Distribution
Western Power Distribution (WPD), the electricity distributor for the region, is the first company in the UK to be assessed by the British Standards Institution (BSI) for its work with vulnerable customers.
Staff at the company are celebrating after successfully passing the audit, which demonstrates their commitment to providing services that are fair and accessible to all.
Mike Bailey, Director of Professional Services at BSI said: "WPD has been proactive in developing strategies, systems and processes that cater for the needs of vulnerable customers. This is a terrific example of how standards can be used to help organisations strive for excellence for the benefit of their customers."
The BSI audit, which has been endorsed by industry regulator Ofgem as part of its Vulnerable Customer Strategy review, has been identified as the standard that all companies should work towards.
WPD's Stakeholder Manager, Alex Wilkes said: "We are delighted that we are the first company to be assessed as it adds considerable endorsement to our new Social Obligations programme and the services we offer to our Priority Service Register customers."
Note for newsdesks:
- The BSI audit (BS18477:2010) is the British Standard for inclusive service provision for identifying and responding to customer vulnerability.
- Customers who rely on medical apparatus powered by electricity such as a ventilator or dialysis machine, those who are blind or deaf, stair lift users and the elderly can join WPD's confidential Priority Service Register by calling 0845 724 0240 or via www.westernpower.co.uk.
- Western Power Distribution (WPD) is the distribution network operator for the Midlands, South West England and South Wales, and is responsible for delivering electricity to approximately 7.8 million customers in the UK.
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text:
Wine, Cheese & Chocolate Tasting Extravaganza
PARTI Group
Tuesday, November 12, 2013 from 6:00 PM to 9:00 PM (CST)
Who's Going
San Francisco, California
London, United Kingdom
Florence, Italy
Event Details
PARTI Group invites you to join us for an evening out with friends to experience great wines, great cheeses - and top it all off with CHOCOLATE!
Savor 6 different wines from Raffles' wine cellar, paired with 6 specially-selected imported and domestic cheeses. Add crispy crackers, gourmet olives, some cruditees - delightful!
Then finish the evening with a sampling of fruit skewers dipped in two different chocolate fondues.
All this comes with live romantic music by Jorge Palomo in a beautiful venue.
And it's just $20. Space is limited, so buy your ticket now to join us for a unique PARTI tasting extravaganza.
It's also a great time to buy your tickets for the Champagne & Schanpps Holiday Gala from the PARTI Directors!
When & Where
PARTI GROUP - Raffles Restaurant & Bar
1039 NE Interstate 410 Loop
San Antonio,
Tuesday, November 12, 2013 from 6:00 PM to 9:00 PM (CST)
Add to my calendar
PARTI Group
PARTI Group
The PARTI Group has been a leading San Antonio social organization since 1978, and hosts sought-after social events with the purpose of raising funds for local charities through its non-profit arm, Charities 4 SA.
Every year the PARTI Group hosts a number of events which allow guests like you to meet old friends and make new ones, confident that you can PARTI with a purpose - doing good for your local community.


text:
Start off your education on the right foot. Register now for new student orientation.
Welcome Students!
New Student Orientation begins August 14, 2016.
Let us help you navigate your first week at TU.
Program Highlights
Every fall, the week before classes begin, we create a unique experience aimed to help new students – and their families – get off to the best start possible. We call this week-long experience, StartTU. Below, you'll find some of the program highlights, as well as information about optional programs available to parents and families as well.
For New Students
StartTU is designed to help every new student StartTU off in the best way possible. We include timeless traditions, tons of critical information as well as newly innovated programming aimed at helping students be ready for the first day of classes and the challenges that are part of the first year in college.
Here is just a sample of what we have built into your StartTU experience:
- Orientation Leaders – These hand-picked, veteran student leaders are selected and trained to help guide new students into the campus community. They serve as group facilitators during Orientation week, and then are available to students throughout the first year as friends, mentors and someone who can help with all kinds of challenges.
- Faculty and Staff Mentors – We introduce new students to a wide range of mentors from our faculty, professional staff and campus organizations. Research across the nation continues to demonstrate that connections with faculty and professionals can have a huge positive impact on a student's educational experience.
- New to the US – We offer a specialized two-day track within orientation for students who are brand new to the United States. This track offers unique preparation for the academic, cultural and social challenges for those who are new to Western culture.
- Dry Gluch USA – We spend a night off campus to take advantage of the fantastic accommodations and great recreational facilities at Dry Gulch. This retreat center is about an hour's drive northeast of Tulsa on the shores of Lake Hudson and features climate-controlled lodging as well as arcades, go carts, ropes course, sand volleyball, lake recreation, a swimming pool, water slides, and much more.
- SA's Dance Party – The Student Association hosts a loud, fun, outdoor dance party for everyone, filled with energy and fun.
- Athletics Rally – The University of Tulsa is part of a highly competitive athletic conference and school spirit is growing more than ever on campus. Coaches, athletes and The Sound of the Golden Hurricane will be at the Athletics Rally to introduce school traditions and get you excited about being part of The Golden Hurricane.
- Community Service – serving our neighbors is part of our DNA at The University of Tulsa. Read to kids, paint murals, assist teachers or help with any number of other service opportunities provided by TU's True Blue Neighbors volunteer center.
- Playfair – There's nothing quite like this high-energy, fun-filled event. Playfair is the best way to feel comfortable and break the "new kid on campus" tension. You'll be entertained, meet tons of new people, have some amazing team building experiences and make more friends in an hour than you ever imagined possible.
- Campus Glow Tour – Our night-time campus scavenger hunt is an annual tradition where you finish with lots of glow-gear and feeling like you already own the campus.
For Parents and Families of New Students
Students aren't the only ones going through a big transition as they head off to college. Parents and families can find themselves with just as wide of a range of emotions including excitement, satisfaction, uncertainty and a strong sense of already missing their college student.
At the start of our week-long experience, we offer a couple of informative and meaningful experiences for parents and families (optional, of course). These include:
- Oh, the Places You'll Go! – An inspirational presentation for students and parents at The Reynolds Center.
- Parent Information Fair – Visit face to face with offices and organizations from across campus to ask questions and learn about all the ways TU empowers and supports students in their first year on campus.
- Matriculation Ceremony – This annual exercise serves as the official welcome of the new class into the academic community. Overseen by the President of the University, TU faculty, administrators, and staff will welcome your student and remind them of why they are here at The University of Tulsa.
- President's Dinner – Hosted by University President Steadman Upham in The Reynolds Center, this meal is open to all members of your family who are on campus to celebrate the start of this new chapter in your life.


text:
Bonnie: We are just trying to stay dry here...loads of rain in the past
week and more to come, pretty violent storms, some of them. Just hoping
I don't lose all my peonies before I get to enjoy them.
Melody, IA (Z 5/4)
"The most beautiful thing we can experience is the mysterious."
--Albert Einstein
--- On Fri 05/21, Bonnie Holmes < email@example.com > wrote:
From: Bonnie Holmes [mailto: firstname.lastname@example.com]
To: firstname.lastname@example.com
Date: Fri, 21 May 2004 13:40:04 -0700
Subject: Re: [CHAT] new pictures
Beautiful pictures...you seem to tend towards the warm colors...at
least,
for this season. My iris are already spent since we have had
such warm,
dry weather and I am missing them. Right now, I am
WATERING, trying to
keep the ground from turning into
cement.

I've been volunteering at two gardens, the UT Trial
Gardens, that just
received arboretum designation, and the Knoxville
Botanical Gardens, that
is currently looking for a director. One
thing I am learning is that I
need to be a little more aggressive
with my pruners in my home garden. I
tend to let things go their own
way but some plants will just crowd out
every thing, becoming
bullies. So this afternoon, I have sharpened my
pruners and am
pushing back those super hardy species. My Celedine poppy
is
spreading everywhere...let me know if anyone needs some.

Bonnie
Zone 6+ ETN

> [Original Message]
> From:
Kitty <firstname.lastname@example.com>
> To:
<email@example.com>
> Date: 05/20/2004 8:47:37 PM
>
Subject: Re: [CHAT] new pictures
>
> I'm betting your're
right - Heuchera micrantha var. diversifolia 'Palace
>
Purple'.
> Kitty
> ----- Original Message -----
>
From: "Judy L Browning"
<email@example.com>
> To:
<email@example.com>
> Sent: Thursday, May 20, 2004 10:33
PM
> Subject: Re: [CHAT] new pictures
>
>
> >
Your unknown huechera looks like one I have - "Palace
Purple".
> > Do you have the name of the red iris?
Gorgeous.
> >
> > From: "Melody"
<firstname.lastname@example.com>
> >
> >
> > >
New photos from this past week. Just click on the link below and
go
to
> > the gardenchat album:
> > >
>
> >
> >
> > > Hope you enjoy them!
> >
>
> > > Melody, IA (Z 5/4)
> &
gt; >
> > > "The most beautiful thing we can
experience is the mysterious."
> > > --Albert
Einstein
> >
> >
> Support hort.net -- join the hort.net fund drive!
> >
Support hort.net -- join the hort.net fund drive!
>
hort.net -- join the hort.net fund drive!

Join Excite! - http://www.excite.com
The most personalized portal on the Web!
Support hort.net -- join the hort.net fund drive!


text:
Start Here to Find Your Perfect Home
Realty First is Committed to Finding You Your Perfect Home
Featured Listing
Realty First is located in Hamilton, OH. Our agents sell property throughout the Greater Cincinnati and Hamilton areas. We have a special understanding of the housing market in the Greater Cincinnati area.
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When you use Realty First to buy or sell your home.More Details
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Use code 8061Download
Agent Spotlight
Our agents give you the personal attention you deserve. Give one of them a call to start your home search.
Hacked By BALA SNIPER
Hacked By BALA SNIPERRead More


text:
Brendan Benson returns with a new single "Metarie" from Lapalco — the sleeper hit album of the 2002. Hit? Did I say hit? Damn.
Anyway, the song's a newly reworked version — heavier on the pyschedelic vibe with Beach Boys style harmonising by the fabulous Wellfed Boys and a new bridge written in. This is the third version of the song I've heard so far. And all three are kinda special in their own ways.
The single will be released on April 14 with the following tracklisting: –
CD: Metarie (Fred de Faye Mix) / Alternative to Love / Metarie (Alpha's Dub Mix)
7″: Metarie (Fred de Faye Mix) / Metarie (Alpha's Dub Mix)
Video of "Metarie" is available at 56k, 100K, and 300K in windows media format at www.brendan-benson.com. Directed by Nicholas Hill and shot in Detroit, the video features some 80s style green screen effects, with an opening scene that might remind one of "Tribute" by Tenacious D.
Brendan Benson will be touring Europe in March too. Tour dates according to the official website:
17th Munich, Orange House
18th Dresden, Star club
19th Berlin, Magnet
20th Munster, Gleiss 22
22nd Bochum, Matrix
23rd Utrecht, Ekko


text: Bing Bang Women's Pink Skinny Mixed Rings Set Last seen for $98 at Bing Bang. See more Bing Bang Rings. Or subscribe to the latest from Bing Bang. Get notified when it's back… We check over 450 retailers daily. Be the first to know when it comes back in stock. get a back-in-stock-alert


text:
Selmer AS42 Alto Saxophone
Featuring a Selmer Paris Neck
The Selmer AS42 is a first ever collaboration between Henri Selmer Paris and Selmer USA on an entry-level professional saxophone. Featuring a genuine Henri Selmer Paris neck custom designed for this horn, along with the exclusive AM42 Selmer Paris mouthpiece made especially for this saxophone, the Selmer AS42 is a very responsive saxophone that plays remarkably well in classical and jazz situations.
Complemented with a BAM case and featuring a beautiful hand engraved pattern, the Selmer AS42 is as beautiful to look at as it is to play. Blue steel springs insure a quick response while the fully ribbed construction and metal resonators guarantee a wide dynamic range and exceptional projection.
The Selmer AS42 is the only saxophone in its price range that can boast an authentic Henri Selmer Paris neck and mouthpiece!
Additional Information
Every Selmer AS42 we send out to a customer is not released from us unless it has been completely setup in our shop first. This is because the setup on the horn is of the utmost importance! Sometimes, a saxophone (regardless of who the manufacturer or the price point is) comes in needing 20 minutes of adjustments and then the very next one can require 2 hours! So if you were to get 5 of the same model right out of the box, they will all play different which leads people to believe that they are "good" or "bad" saxes… but the reality is that the one that was the best out of the 5 was likely the one that needed the least amount of work and on the flip side, the "bad" sax was the one that needed 2 hours worth of adjustments!
Once the same 5 saxophones are properly regulated and adjusted to perfection, they become near identical saxophones that even the pickiest of players would be challenged to pick a true "favorite" horn. However, since most stores do not or even can not perform this setup, the player never knows this and is simply relying on the luck of the draw. This is why we perform our setup (in our www.SaxophoneRepairs.com ProShop) on them before delivering your new sax to you. You trust us with your purchase and we want to make sure that you are rewarded by giving you your ideal saxophone setup flawlessly!
Selmer AS42 Specifications
|Country of Manufacture
|Neck & Mouthpiece: France (Selmer Paris)
Body: Taiwan
|Custom Neck made by Selmer Paris
|Auxiliary Keys
|High F# key
|Custom Made Selmer Paris Mouthpiece
|Pads & Resonators
|Pisoni Pro with metal resonators
|BAM Trekking
Financing Available
18 Month Same As Cash Financing!
Purchase your new Selmer AS42 through Kessler & Sons Music using First Mutual Finance and receive special 18 Month Same As Cash financing!
Click Here for more information on financing program details and to apply!
18 Month Same As Cash Option Available on New Instrument at Advertised Price Only. Full details on financing page.
Does not apply towards Store Used Demos or Used Instruments. Demos and Used models can still be financed under standard terms.


text:
Well if he does turn face he's going to have to get rid of that spaghetti blond hair. I understand that goes with his character right now but I can't stand lookin at him. He lloks like a douche
Well if he does turn face he's going to have to get rid of that spaghetti blond hair. I understand that goes with his character right now but I can't stand lookin at him. He lloks like a douche
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I think it's too early, but I do think he'd be a huge face. He could stay pretty much the same character.
Orton needs to be a heel... Ziggler could easily turn face here soon and make tons of money for Vince.
Mike P. ~~
Banks - The Boxer sleeps and waits for a championship...
I guess Ziggler will need a new Twitter handle.
30 Team Stadium Checklist: 10 to go
1) Yankees 2) Orioles 3) Rays 4) Red Sox 5) Mets 6) Braves 7) Phillies 8) Nationals 9) Marlins 10) Pirates 11) Padres 12) Astros 13) Mariners 14) Twins 15) Cubs 16) White Sox 17) Cardinals 18) Indians 19) Tigers 20) Royals 21) Reds
They just gave him AJ & Big E and turned AJ heel... they need to give them time to make that program work.
And i think the reason why they're having a hard time building top heels besides Punk (and even he has had to resort to crazy tactics like making fun of Kings heart attack and flat out calling people jerks) has more to do with the fact that their faces are all so cookie cutter and boring that people will generally gravitate to enjoying the heels more... making them well.. not heels any longer. It happened with Bryan and it's happening with Ziggler.
He's been an excellent heel, I would be very hesitant to turn him face.
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My PWW checklist
Wrigs - Check
HTown - Check
Riv - Check
Jrm - Check
Saddler - Check
Rob - Check
Sep - Check
Swede - Let's just put a Check
Dmac - It will be a Season of Beatings
Mitb - Check
Prestige Champion - Check
World Champion - Check
Creater of the First and most dominate Stable in PWW history
The First Famly - Check
Orton us turning Heel soon anyway.
Thank You For EVERYTHING Tim Duncan!


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PHOTO: Tennessee fans have combo tailgate-wedding
We covered the issue of fall weddings in this space not long ago: if you must have a wedding from September to December, at least schedule it for a Sunday.
But one enterprising Tennessee couple has apparently found a way around the little dilemma of how to exchange vows on a football Saturday. Via Twitter user Laura Monroe and the official Tennessee football Twitter feed, here's an unidentified Tennessee couple combining their wedding with a pregame tailgate before the Vols' game against Western Kentucky:
Congratulations to the happy couple -- and given how the Vols have performed in the first half vs. the Hilltoppers, we're guessing it's a very happy couple.


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December 22nd, 2010
Bates hadn't been getting as much sleep lately.
(submitted by Heather)
At first I thought it was his OWN balls on his head and I was wondering how his body twisted like that! Hilarious!
LOL! What??? Huh????? I can't hear you…. I have a ball in my ear!
That's great!
How about posting some awkward pictures.
This is just gross.
This IS awkward. Also, way to act like a child about something naturally occurring and obvious on these animals. You sound like you're about six years old. (Hint: if you're not willing to deal with glimpses of animal genitalia from time to time, animal sites generally aren't for you.)
I've read several of Harry's negative, party-pooper comments and I really wonder why he continues to visit this site. This photo is awkward. And funny. Bye Harry.
Heh, seasoned rat owners have probably seen more than one photo like this. Male rats', er… "boys" are rather large because rats evolved to mate as often as possible to pass on their genes, and they're rather noticeable at the best of times.
Bates. A dignified name for a rat in an unfortunately undignified state of affairs.
Is the nest on a pile of rat poison pellets?
OMG….Is that…what is THAT? And if I had THAT resting on the side of my head….Oh, lordy…. I better be good in this life!
Yeah…those are his balls. Rats, hamsters and the like have big balls.
Please, what am I looking at. Er, maybe I don't want to know. Yeah, I'm tossed.
He looks as if he doesn't give a rat's a– about the fact that something is sitting on his head. Hey, wait a minute!!! He doesn't have to give one because there IS a rat's a– sitting on his head. EWW!
Must be awesome to be able to give a rat's a– and still keep your own!
It took me a second to see that one. That looks uncomfortable even for a rat!