text:
Analysis of bronchoalveolar lavage fluid proteome from systemic sclerosis patients with or without functional, clinical and radiological signs of lung fibrosis
DOI: 10.1186/ar2067
© Fietta et al.; licensee BioMed Central Ltd. 2006
Received: 7 March 2006
Accepted: 17 October 2006
Published: 17 October 2006
Lung fibrosis is a major cause of mortality and morbidity in systemic sclerosis (SSc). However, its pathogenesis still needs to be elucidated. We examined whether the alteration of certain proteins in bronchoalveolar lavage fluid (BALF) might have a protective or a causative role in the lung fibrogenesis process. For this purpose we compared the BALF protein profile obtained from nine SSc patients with lung fibrosis (SScFib+) with that obtained from six SSc patients without pulmonary fibrosis (SScFib-) by two-dimensional gel electrophoresis (2-DE). Only spots and spot-trains that were consistently expressed in a different way in the two study groups were taken into consideration. In total, 47 spots and spot-trains, corresponding to 30 previously identified proteins in human BALF, showed no significant variation between SScFib+ patients and SScFib- patients, whereas 24 spots showed a reproducible significant variation in the two study groups. These latter spots corresponded to 11 proteins or protein fragments, including serum albumin fragments (13 spots), 5 previously recognized proteins (7 spots), and 4 proteins (3 spots) that had not been previously described in human BALF maps, namely calumenin, cytohesin-2, cystatin SN, and mitochondrial DNA topoisomerase 1 (mtDNA TOP1). Mass analysis did not determine one protein-spot. The two study groups revealed a significant difference in BALF protein composition. Whereas levels of glutathione S-transferase P (GSTP), Cu–Zn superoxide dismutase (SOD) and cystatin SN were downregulated in SScFib+ patients compared with SScFib- patients, we observed a significant upregulation of α1-acid glycoprotein, haptoglobin-α chain, calgranulin (Cal) B, cytohesin-2, calumenin, and mtDNA TOP1 in SScFib+ patients. Some of these proteins (GSTP, Cu–Zn SOD, and cystatin SN) seem to be involved in mechanisms that protect lungs against injury or inflammation, whereas others (Cal B, cytohesin-2, and calumenin) seem to be involved in mechanisms that drive lung fibrogenesis. Even if the 2-DE analysis of BALF did not provide an exhaustive identification of all BALF proteins, especially those of low molecular mass, it allows the identification of proteins that might have a role in lung fibrogenesis. Further longitudinal studies on larger cohorts of patients will be necessary to assess their usefulness as predictive markers of disease.
The analysis of the bronchoalveolar lavage fluid (BALF) proteome can potentially provide important information about changes in protein expression and secretion during the course of pulmonary disorders. At the moment, more than 100 human proteins or protein isoforms have been identified in human BALF by using two-dimensional gel electrophoresis (2-DE), including both proteins released locally in the lung by inflammatory or epithelial cells and proteins derived from serum by diffusion across the capillary–alveolar barrier [1, 2]. Previous studies showed that the protein composition of BALF was altered in sarcoidosis, idiopathic pulmonary fibrosis, allergic asthma, and chronic obstructive pulmonary disease [3–5]. Furthermore, Rottoli and colleagues [6] recently demonstrated that systemic sclerosis patients with pulmonary fibrosis (SScFib+) showed a BALF profile that was intermediate between that of patients with sarcoidosis and idiopatic pulmonary fibrosis, despite some particularities.
Systemic sclerosis (SSc) is an autoimmune disorder of unknown origin, characterized by an excessive deposition of collagen and other extracellular matrix proteins on the skin as well as multiple internal organs, alterations in microvasculature, and humoral and cellular abnormalities [7]. Clinically, the disease is very heterogeneous, ranging from limited skin involvement with limited systemic alterations to clinical pictures with diffuse skin sclerosis and severe visceral involvement with fibrosis, microvascular abnormalities and mononuclear cell infiltration of the gastrointestinal tract, lungs, heart, and kidneys. Pulmonary involvement has emerged as potentially the most serious visceral lesion in SSc. Alveolitis is more commonly seen in SSc with diffuse skin sclerosis, particularly in the presence of serum anti-topoisomerase I (anti-Scl70) antibodies, but only 15% of patients eventually reach severe end-stage lung fibrosis [8].
Given the complexity of the pathogenesis of lung fibrosis and the lack of biological markers that can reliably predict which patients will evolve the disease, great interest has been shown in these issues, also comparing cohorts of SSc patients with or without lung involvement. The ability to identify the proteins that are differently expressed in the lower airways of SScFib+ patients from those in SScFib- patients might provide new insight into the disease pathogenesis and into the identification of possible protein biomarkers of the disease's progression. With this aim, we used the 2-DE analysis to assess and compare the protein profile of BALFs from a group of SScFib+ and SScFib- patients, respectively.
Materials and methods
The samples consisted of archived BALF samples acquired between March 2004 and April 2005 from 15 SSc patients who satisfied the preliminary American College of Rheumatology criteria for disease classification [9]. All the patients were female and non-smoker outpatients at the Rheumatology Unit of the Policlinico San Matteo, Pavia, Italy. They all gave their informed consent to undergo bronchoscopy, and none were being treated with prednisone or other immunosuppressive agents at the time of enrollment. Five patients had SSc with limited skin involvement and 10 had SSc with diffuse skin sclerosis; indirect immunofluorescence on Hep-2 cells detected the antinuclear antibodies, and the anti-Scl70 antibodies were evaluated by enzyme-linked immunosorbent assay (Diamedix Co., Miami, FL, USA). All the patients tested positive for antinuclear antibodies, and nine had anti-Scl70 antibodies.
Demographic, clinical, immunological and functional characteristics of scleroderma patients
Age, years (mean ± SD)
55.6 ± 10.3
50.5 ± 9.6
Cutaneous involvement
Lc SSc (percentage)
1 (11.1)
4 (66.7)
Dc SSc (percentage)
8 (89.9)
2 (33.3)
Skin score (mean ± SD)
17.0 ± 8.0
10.0 ± 6.0
ANA positive (percentage)
9 (100)
6 (100)
Anti-Scl70 positive (percentage)
7 (77.7)
2 (33)
Lung function test
FVC, percentage predicted (mean ± SD)
80.9 ± 11.7a
118.7 ± 11.6
TLCO, percentage predicted (mean ± SD)
60.01 ± 12.6a
72.03 ± 13.8
Kazerooni score
10.0 ± 5
Bronchoalveolar lavage and phenotype analysis
Bronchoalveolar lavage (BAL) was performed as described previously [13]. To summarize briefly, the distal tip of the bronchoscope was wedged into the middle lobe or lingular bronchus. A total of 150 ml of warm sterile saline solution were instilled in 30 ml aliquots and serially recovered by gentle aspiration. The first collected aliquot was used for the microscopic and cultural examination of common bacteria and fungi, and of direct acid-fast bacilli smears (Kinyoun method) and cultures for mycobacteria, and for the microscopic examination of Pneumocystis jiroveci (Gomori-Grocott silver stain). All the other aliquots were used to assess the total and differential cell counts (performed on cyto-centrifuged preparations with the use of May–Grünwald–Giemsa and Papanicolaou stainings) and the percentages of CD4+ and CD8+ T cells (assessed by cytofluorimetry). Samples were immediately filtered twice through gauze, then centrifuged at 1,500 r.p.m. for 10 min, and BALF samples were promptly frozen in aliquots and stored at -80°C until used.
Two-dimensional gel electrophoresis
BALF samples were dialyzed (tubing cut-off 1 kDa) for a few days against several changes of distilled water, in the presence of protease inhibitors (protease inhibitor cocktail; Sigma, St Louis, MO, USA), and the protein content was assessed (bicinchoninic acid protein assay kit; Pierce, Rockford, IL, USA). Samples were freeze-dried and pellets were suspended in 8 M urea, 4% w/v CHAPS, 65 mM 1,4-dithioerythritol (solution A). Two-dimensional gel electrophoresis was performed as described previously [14]. In brief, for each analytical experiment the same amount (70 μg) of proteins was loaded on immobilized pH gradient (IPG) strips (pH 3.5 to 10, 18 cm; Amersham Biosciences, Uppsala, Sweden), which were swollen in solution A plus 0.8% carrier ampholytes (Ampholine™, pH 3.5 to 10 for IEF; Amersham Biosciences) and a trace of bromophenol blue. A larger amount of protein (1 mg) had to be loaded for identification by mass spectrometry (MS). Rehydration was performed in the strip holder of the IPGphor system at 20°C (Amersham Biosciences) and isoelectrofocusing was terminated at 60 kV h. The IPG strips were equilibrated first for 12 minutes in urea/SDS/Tris buffer, and then in the same buffer containing 2.5% (w/v) iodoacetamide. The run in the second dimension was performed on 9 to 16.5% polyacrylamide linear gradient gels with a constant current of 40 mA per gel at 10°C. The gels were stained with ammoniacal silver nitrate or colloidal Coomassie G-250 [15].
Evaluation and protein identification
The Versadoc Imaging System Model 3000 (Bio-Rad, Richmond, CA, USA) scanned the gels, which the PD QUEST 7.1 software (Bio-Rad) then analyzed. The total number of spots, the non-matched spots and the spot parameters were measured. To detect differentially expressed protein spots in SScFib+ compared with those in SScFib- patients, the software was instructed to create one reference map for each patient group. The software established these maps by taking into account only the spots that were constantly expressed in each patient of the same group. At least two gels from each patient were evaluated. Initially, we compared the two reference maps so as to assess differences in spot quantity between the two study groups. The PD QUEST 7.1 software determined the spot quantity by formula: Spot height × π × σ x × σ y (where the spot height represented the peak of the spot's Gaussian representation, and σ x and σ y were the SD of the spot's Gaussian distribution in the directions of the x and y axes, respectively) normalized the value for the total protein content of each gel. The differences between the two study groups were then confirmed by analysing the spot quantities observed in single patients. On the basis of the recent guidelines for proteomics research [16], non-matched spots and spots that differed significantly in quantity (p < 0.05) were regarded as differentially expressed in SScFib+ compared with SScFib- patients.
Proteins were identified by comparing the BALF maps obtained in this study with the SWISS-2D PAGE human plasma map [17] and published BALF maps [5, 6], using immunoblotting, matrix-assisted laser desorption/ionization MS, and/or liquid chromatography MS/MS. For the MS analysis, the selected spots, excised from Coomassie-stained gels, were analyzed in a Voyager DE-PRO mass spectrometer (Applied Biosystems, Foster City, CA, USA), equipped with a reflectron analyzer and used in delayed extraction mode. Mass signals were used for database searching with the MASCOT peptide fingerprinting search program (Matrix Science, Boston, MA, USA). A quadrupole time-of-flight. Ultima hybrid mass spectrometer (Micromass, Toronto, Ontario, Canada) was used for the liquid chromatography–MS/MS analysis. The instrument was set up in a data-dependent MS/MS mode, and the raw MS and MS/MS spectra were elaborated with ProteinLynx software. The MASCOT MS/MS ion search software for protein identification was used. These evaluations were performed at CEINGE Biotecnologie Avanzate s.c. a r.l., University Federico II, Naples, Italy).
Statistical methods
Results are presented as mean ± SD or median and interquartile range. Normally distributed variables were analyzed by a two-tailed Student's t test. Proteomics expression data were compared by using the Mann–Whitney U test. For all tests p < 0.05 was regarded as significant. Analyses were performed with PRISM 3.0 (GraphPad Software, San Diego, CA, USA).
Cytology, CD4+/CD8+ T-cell ratio and protein contents of bronchoalveolar lavage samples
SScFib+ (n = 9)
SScFib- (n = 6)
Controls (n = 9)
Total BAL cells (105/ml)
2.05 ± 1.13
1.80 ± 0.74
2.02 ± 1.33
Macrophages (percentage)
84.97 ± 8.66
87.73 ± 5.12
85.78 ± 7.09
Lymphocytes (percentage)
8.01 ± 4.15
7.80 ± 2.63
12.33 ± 6.36
Neutrophils (percentage)
4.44 ± 4.03a
2.76 ± 1.98
1.56 ± 1.59
Eosinophils (percentage)
2.62 ± 3.66a
0.83 ± 0.60
0.33 ± 0.70
CD4+/CD8+ ratio
2.30 ± 1.02
2.14 ± 1.16
2.4 ± 0.71
Protein concentration (μg/ml)
130.44 ± 53.76
133.43 ± 32.38
BALF proteome in SScFib+ and SScFib-patients
Proteins whose quantity in BALF did not significantly vary between SScFib+ and SScFib- patients
Spot no.
Identification method
1β glycoprotein
Ig heavy chain α
Vitamin D-binding protein
GM, Ab
GM, Ab
Leucin-rich α2-glycoprotein
Fibrinogen γ A chain
GM, Ab
Ig heavy chain γ
Haptoglobulin 1β chain
Pulmonary surfactant-associated protein A
Apolipoprotein A1
GM, Ab
Ig light chain κ, λ
GM, Ab
Serum retinol-binding protein
GM, Ab
Immunoglobulin-binding factor
Calgranulin A
Hemoglobin β chain
ERP60 (protein disulfide isomerase)
GM, Ab
α1-antitrypsin (fragment)
GM, Ab
Ig J chain
C-reactive protein
Apolipoprotein A1 (fragment)
GM, Ab
TCTP (translationally controlled tumor protein)
ATP synthase δ chain mitochondrial
L-FABP (liver fatty acid-binding protein)
BALF proteins whose regulation in SScFib+ and SScFib- patients is different
Spot no.
Median (IQR) spot quantity
Protein or fragment
MW (kDa)
Identification method
328.0 (256.5–482.5)
86.0 (68.6–110.4)
α1-acid glycoprotein (orosomucoid)
GM (plasma, BALF), Ab
7.9 (5.6–9.6)
28.2 (24.5–32.6)
Cu–Zn superoxide dismutase
GM (plasma, BALF), Ab
343.0 (328.5–664.0)
168.0 (131.5–267.0)
Serum albumina
96.6 (68.9–127.6)
24.4 (17.2–64.5)
Calgranulin B (S100A9; MRP14)
MS, GM (plasma, BALF)
53.3 (47.4–72.1)
11.1 (8.0–22.9)
Haptoglobin (Hp2) α chaina
MS, LC, GM (plasma, BALF)
Not expressed
32.0 (29.5–39.0)
Glutathione S transferase P
MS, GM (plasma, BALF)
59.1 (50.8–73.1)
14.8 (9.4–19.6)
29.2 (25.5–30.8)
Not expressed
Mitochondrial DNA topoisomerase 1a,b
Not expressed
45.5 (32.2–58.9)
Cystatin SNb
Not expressed
37.7 (34.0–41.0)
Not determined
The pathogenesis of SSc is extremely complex, and no single unifying hypothesis or pathogenetic mechanism can explain all the aspects of this disease. It is therefore widely accepted that functional alterations of several cell effectors, including fibroblasts, endothelial cells, and T and B lymphocytes, are intimately involved in the development of the clinical and pathological manifestations of SSc [7, 18, 19]. Abnormalities in lung function occur in about 70% of SSc patients and currently represent the main cause of mortality in this population [7]. However, the factors that drive the severe and progressive visceral fibrosis remain mostly undetermined. Unlike the recent pathogenetic hypothesis for idiopathic interstitial lung fibrosis, which assigns only a marginal role to inflammation, fibrogenesis in SSc-related lung involvement is generally thought to be the result of a complex series of interstitial immunoinflammatory reactions [20]. The persistent and unregulated activation of genes that encode various collagen and other extracellular matrix proteins is regarded as a crucial pathogenetic event [21, 22]. Furthermore, an alteration in the production of pro-inflammatory and/or pro-fibrotic cytokines and chemokines, growth factors (in particular transforming growth factor-β), and signaling molecules also seems to have a relevant role in fibrogenesis [23, 24]. The identification of proteins that are differently expressed in the airways of SScFib+ patients compared with patients with no signs or symptoms of lung involvement may cast light on the pathogenetic mechanism of the disease and may thereby indicate protein biomarkers that are useful for the diagnosis of lung involvement, for the monitoring of SSc progression, and for the identification of possible new therapeutic targets. In this context, the use of 2-DE and the mapping of BALF seem highly interesting.
Our results demonstrated that quantitative and qualitative differences can be found between patients with SSc-associated lung fibrosis and patients with SSc with no signs or symptoms of lung involvement. At least 24 well-defined spots showed significant and reproducible variations in relative abundance between the two patient groups. Some of these spots corresponded to previously described BALF proteins and protein fragments, namely α1-acid glycoprotein, GSTP, Cu–Zn SOD, haptoglobin-α chain, and calgranulin B, whereas 4 of the proteins found had not previously been described in published two-dimensional BALF maps, namely cytohesin-2, calumenin, cystatin SN, and human mtDNA TOP1 fragment. In SScFib+ patients, GSTP and cystatin SN were below the detection limit, whereas Cu–Zn SOD was downregulated. In contrast, α1-acid glycoprotein, calumenin, cytohesin-2, haptoglobin-α chain, and calgranulin B were significantly upregulated, and the expression of mtDNA TOP1 was observed only in SScFib+ patients.
On the basis of these preliminary results, we can infer that 2-DE analysis of BALF can provide useful insight into the understanding of mechanisms involved in lung fibrogenesis through the identification of proteins that are deregulated in SSc-associated lung fibrosis. However, our results, as well as those of previous studies, clearly indicated that 2-DE analysis did not provide an exhaustive identification of all proteins that can be present in BALF, especially those of low molecular mass such as cytokines, chemokines, growth factors, and signaling molecules. Because these molecules are thought to be relevant to the pathogenesis of SSc-associated lung fibrosis, a combination of 2-DE analysis and proteomic approaches that specifically address the identification of these factors is necessary for the assessment of the whole protein pattern of BALF. Despite these considerations, most of the proteins we found differently regulated between SScFib+ patients and SScFib- patients could have a role in the development of lung fibrosis, whereby some of them are involved in the mechanisms that protect against lung injury or inflammation whereas others are involved in the mechanisms that drive fibroproliferation.
Oxidative stress is believed to be important in the pathogenesis of lung damage and in the development of lung fibrosis [25]. Among various enzymatic and non-enzymatic mechanisms that protect cells and tissues from oxidants [26, 27], glutathione transferases [28] and SODs [29] are among such mechanisms that are thought to have a key protective role, especially in the lung. High levels of extracellular SODs are thought to have a protective role for lung matrix [29]. Recently, Tourkina and colleagues [30] demonstrated a deficiency in GSTP1 in scleroderma lung fibroblasts. The observation that GSTP and Cu–Zn SOD levels are severely downregulated in BALF from SScFib+ patients is in line with these findings, and confirms the relevance of these molecules as a defense tool for the lung against oxidant-induced damage and/or fibroproliferation.
Moreover, in BALF from SScFib+ patients, we did not detect levels of cystatin SN, which was, in contrast, well represented in SScFib- patients. Cystatin SN is a secreted protein, which belongs to SD-type or type-2 cystatins [31], which are potent inhibitors of CA clan mammalian cysteine peptidases. Intracellularly, these enzymes participate in normal protein turnover, in antigen and protein processing, and in apoptosis, whereas extracellularly they are involved in the inhibition of the proteolytic cascade [32]. The direct inhibition of endogenous and exogenous cysteine peptidases is the only function described so far for cystatin SN, suggesting that its function is to protect tissues against injury induced by these enzymes. However, recent results obtained with other type-2 cystatins seem to suggest a broader spectrum of activities, including the upregulation of IL-6 by human gingival fibroblasts, interferon-γ expression in CD4+ T cells [33, 34], and the involvement in the differentiation and maturation of human dendritic cells [35].
Furthermore, we found an upregulation of at least six proteins in BALF from SScFib+ patients: haptoglobin-α chain, α1-acid glycoprotein, calumenin, cytohesin-2, Cal B, and mtDNA TOP1.
Haptoglobin and α1-acid glycoprotein are positive acute-phase proteins, whose plasma concentrations increase during inflammation [36]. The increased levels of both proteins in BALF from SScFib+ patients is likely to originate from the passive diffusion from plasma, as a result of the increased permeability of the air–blood barrier during the course of fibrosing alveolitis.
Calumenin is a member of the CREC family [37] that is secreted into the medium of cultured cells including fibroblasts [38] and early melanosomes [39]. Intracellularly, calumenin has a chaperone function in several Ca2+-regulated processes, but extracellularly its function is not yet fully understood. Vorum and colleagues found that calumenin binds to the serum amyloid P component, suggesting that it is involved in the formation of amyloid deposits in different tissues [40]. Coppinger and colleagues recently described the presence of calumenin in platelets and its release on platelet activation, as well as the protein's presence in human atherosclerotic lesions [41], therefore suggesting a possible role of this protein in leading to vascular injury through the promotion of platelet adhesion, fibrinogenesis, and intravascular thrombus deposition. Taking into account that a crucial pathogenetic step in SSc involves injury to microvasculature [19, 20], it is possible to infer that calumenin could have a role in taking such an injury to lung level.
Cytohesin-2 is a member of a family of cytoplasmic signaling proteins [42], which may move from the cytosol to the plasma membrane after cell stimulation [43]. Although its biological function is mostly unknown, a recent study demonstrated that cytohesin-2 is an activator of the mitogen-activated protein (MAP) kinase signaling pathway [44]. Because MAP kinases are activator signals for lung fibroblasts [23], we suggest that cytohesin-2 might participate in the development and/or progression of lung fibrosis in SSc patients through the activation of the MAP kinase signaling pathways in lung fibroblasts. This hypothesis needs to be verified with further experimental observations.
Calgranulin B is an S100 protein that is unique together with Cal A in its myeloid-specific expression profile and in its abundance in neutrophils [45]. Increased levels of Cal B are present in the bronchial secretion of patients with chronic inflammatory disease, and these levels may induce the production of IL-8 by airway epithelial cells [46]. Furthermore, Viemann and colleagues demonstrated that the expression of Cal B and Cal A correlates with the inflammatory activity in systemic vasculitis, thereby confirming the role of these proteins in inflammatory reactions of endothelia [47]. Although the general consensus is that the Cal B function depends mainly on heterodimer formation (Cal B–Cal A), several studies have demonstrated that the monomer is also a potent stimulator of neutrophils and is involved in the recruitment of leukocytes to the site of inflammation through the regulation of adhesion and the extravasion of neutrophils [45, 48]. Furthermore, recombinant Cal B and its homodimer stimulate the proliferation of rat fibroblasts, suggesting that this protein might also function as a mitogen for fibroblasts in chronic inflammation [49]. On the basis of these observations, Cal B could have a role in SSc-associated lung fibrosis through several pathways, including amplifying the inflammatory process by inducing the extravasion of neutrophils and the production of IL-8, inducing an inflammatory reaction in the endothelia, and/or stimulating lung fibroblast proliferation.
Finally, we found that a fragment of mtDNA TOP1 was detectable only in BALF from patients with interstitial lung fibrosis, including in two SScFib+ patients who were negative for serum anti-Scl70 antibodies. This protein fragment was never observed in BALF from SScFib- patients, including in two patients with positive anti-Scl70 antibodies. A common 13-exon motif and a similar amino-acid sequence characterize genes for mitochondrial and nuclear DNA TOP1, except for the N-terminal domain, which in mtDNA TOP1 contains a mitochondrial localization sequence instead of the nuclear localization signal [50]. Although we demonstrated that the presence of detectable levels of mtDNA TOP1 was a constant and particular feature of SScFib+ patients, we did not fully ascertain the antigenic role of this protein fragment and its relation with the development of lung fibrosis. Because autoantibodies against DNA TOP1 are strongly correlated with interstitial pulmonary involvement in SSc [51], further studies are warranted to assess the role and the frequency of this antigenic target in BALF.
- Anti-Scl70:
= anti-topoisomerase I antibodies
= bronchoalveolar lavage
= bronchoalveolar lavage fluid
- Cal:
= calgranulin
= two-dimensional gel electrophoresis
= glutathione S-transferase P
= high-resolution computed tomography
= interleukin
= immobilized pH gradient
= mitogen-activated protein
mass spectrometry
- mtDNA TOP1:
= mitochondrial DNA topoisomerase 1
= superoxide dismutase
- SSc:
= systemic sclerosis
- SScFib-:
= systemic sclerosis patients without lung fibrosis
- SScFib+:
= systemic sclerosis patients with lung fibrosis
= carbon monoxide transfer.
We thank Dr Angela Flagiello for help with mass analysis, and Professor Piero Pucci for insightful comments on the manuscript. This work was supported by Fondazione Cariplo, Italy (Grant Rif.2003.1644/10.8485).
Authors' Affiliations
- Wattiez R, Hermans C, Bernard A, Lesur O, Falmagne P: Human bronchoalveolar lavage fluid: two-dimensional gel electrophoresis, amino acid microsequencing and identification of major proteins. Electrophoresis. 1999, 20: 1634-1645. 10.1002/(SICI)1522-2683(19990601)20:7<1634::AID-ELPS1634>3.0.CO;2-J.View ArticlePubMedGoogle Scholar
- Wattiez R, Hermans C, Cruyt C, Bernard A, Falmagne P: Human bronchoalveolar lavage fluid protein two-dimensional database: study of interstitial lung diseases. Electrophoresis. 2000, 21: 2703-2712. 10.1002/1522-2683(20000701)21:13<2703::AID-ELPS2703>3.0.CO;2-W.View ArticlePubMedGoogle Scholar
- Magi B, Bini L, Perari MG, Fossi A, Sanchez JC, Hochstrasser D, Paesano S, Raggiaschi R, Santucci A, Pallini V, et al: Bronchoalveolar lavage fluid protein composition in patients with sarcoidosis and idiopathic pulmonary fibrosis: a two-dimensional electrophoretic study. Electrophoresis. 2002, 23: 3434-3444. 10.1002/1522-2683(200210)23:19<3434::AID-ELPS3434>3.0.CO;2-R.View ArticlePubMedGoogle Scholar
- Sabounchi-Schutt F, Astrom J, Hellman U, Eklund A, Grunewald J: Changes in bronchoalveolar lavage fluid proteins in sarcoidosis: a proteomics approach. Eur Respir J. 2003, 21: 414-420.View ArticlePubMedGoogle Scholar
- Wattiez R, Falmagne P: Proteomics of bronchoalveolar lavage fluid. J Chromatogr B Analyt Technol Biomed Life Sci. 2005, 815: 169-178.View ArticlePubMedGoogle Scholar
- Rottoli P, Magi B, Perari MG, Liberatori S, Nikiforakis N, Bargagli E, Cianti R, Bini L, Pallini V: Cytokine profile and proteome analysis in bronchoalveolar lavage of patients with sarcoidosis, pulmonary fibrosis associated with systemic sclerosis and idiopathic pulmonary fibrosis. Proteomics. 2005, 5: 1423-1430. 10.1002/pmic.200301007.View ArticlePubMedGoogle Scholar
- Jimenez SA, Derk CT: Following the molecular pathways toward an understanding of the pathogenesis of systemic sclerosis. Ann Intern Med. 2004, 140: 37-50.View ArticlePubMedGoogle Scholar
- Basu D, Reveille JD: Anti-scl-70. Autoimmunity. 2005, 38: 65-72.View ArticlePubMedGoogle Scholar
- Subcommittee for Scleroderma Criteria of the American Rheumatism Association Diagnostics and Therapeutic Criteria Committee: Preliminary criteria for the classification of systemic sclerosis (scleroderma). Arthritis Rheum. 1980, 21: 581-590.Google Scholar
- Medsger TA, Silman AJ, Steen VD, Black CM, Akesson A, Bacon PA, Harris CA, Jablonska S, Jayson MI, Jimenez SA, et al: A disease severity scale for systemic sclerosis: development and testing. J Rheumatol. 1999, 26: 2159-2167.PubMedGoogle Scholar
- Kazerooni EA, Martinez FJ, Flint A, Jamadar DA, Gross BH, Spizarny DL, Cascade PN, Whyte RI, Lynch JP, Toews G: Thin-section CT obtained at 10-mm increments versus limited three-level thin-section CT for idiopathic pulmonary fibrosis: correlation with pathologic scoring. AJR Am J Roentgenol. 1997, 169: 977-983.View ArticlePubMedGoogle Scholar
- Meloni F, Caporali R, Marone Bianco A, Paschetto E, Morosini M, Fietta AM, Patrizio V, Bobbio-Pallavicini F, Pozzi E, Montecucco C: BAL cytokine profile in different interstitial lung diseases: a focus on systemic sclerosis. Sarcoidosis Vasc Diffuse Lung Dis. 2004, 21: 111-118.PubMedGoogle Scholar
- Report of the European Society of Pneumology Task Group: Technical recommendations and guidelines for bronchoalveolar lavage (BAL). Eur Respir J. 1989, 2: 561-585.Google Scholar
- Görg A, Postel W, Günther S: The current state of two-dimensional electrophoresis with immobilized pH gradients. Electrophoresis. 1988, 9: 531-546. 10.1002/elps.1150090913.View ArticlePubMedGoogle Scholar
- Candiano G, Bruschi M, Musante L, Santucci L, Ghiggeri GM, Carnemolla B, Orecchia P, Zardi L, Righetti PG: Blue Silver: a very sensitive colloidal Coomassie G-250 staining for proteome analysis. Electrophoresis. 2004, 25: 1327-1333. 10.1002/elps.200305844.View ArticlePubMedGoogle Scholar
- Wilkins MR, Appel RD, Van Eyk JE, Chung MCM, Gorg A, Hecker M, Huber LA, Langen H, Link AJ, Paik Y, et al: Guidelines for the next 10 years of proteomics. Proteomics. 2006, 6: 4-8. 10.1002/pmic.200500856.View ArticlePubMedGoogle Scholar
- ExPASY Proteomics Server. [http://www.expasy.ch/]
- Ludwicka-Bradley A, Bogatkevich G, Silver RM: Thrombin-mediated cellular events in pulmonary fibrosis associated with systemic sclerosis (scleroderma). Clin Exp Rheumatol. 2004, 2 (3 Suppl 33): S38-S46.Google Scholar
- Kahaleh MB: Vascular involvement in systemic sclerosis (SSc). Clin Exp Rheumatol. 2004, 2 (3 Suppl 33): S19-S23.Google Scholar
- Steen VD: The lung in systemic sclerosis. J Clin Rheumatol. 2005, 11: 40-46. 10.1097/01.rhu.0000152147.38706.db.View ArticlePubMedGoogle Scholar
- Pannu J, Trojanowska M: Recent advances in fibroblast signaling and biology in scleroderma. Curr Opin Rheumatol. 2004, 16: 739-745. 10.1097/01.bor.0000137894.63091.1a.View ArticlePubMedGoogle Scholar
- Postlethwaite AE, Shigemitsu H, Kanangat S: Cellular origins of fibroblasts: possible implications for organ fibrosis in systemic sclerosis. Curr Opin Rheumatol. 2004, 16: 733-738. 10.1097/01.bor.0000139310.77347.9c.View ArticlePubMedGoogle Scholar
- Christner PJ, Jimenez SA: Animal models of systemic sclerosis: insights into systemic sclerosis pathogenesis and potential therapeutic approaches. Curr Opin Rheumatol. 2004, 16: 746-752. 10.1097/01.bor.0000137893.68929.86.View ArticlePubMedGoogle Scholar
- Atamas SP, White B: The role of chemokines in the pathogenesis of scleroderma. Curr Opin Rheumatol. 2003, 15: 772-777. 10.1097/00002281-200311000-00015.View ArticlePubMedGoogle Scholar
- Kinnula VL, Fattman CL, Tan RJ, Oury TD: Oxidative stress in pulmonary fibrosis: a possible role for redox modulatory therapy. Am J Respir Crit Care Med. 2005, 172: 417-422. 10.1164/rccm.200501-017PP.PubMed CentralView ArticlePubMedGoogle Scholar
- Kinnula VL: Focus on antioxidant enzymes and antioxidant strategies smoking in related airway diseases. Thorax. 2005, 60: 693-700. 10.1136/thx.2004.037473.PubMed CentralView ArticlePubMedGoogle Scholar
- Comhair SA, Erzurum SC: Antioxidant responses to oxidant-mediated lung diseases. Am J Physiol Lung Cell Mol Physiol. 2002, 283: L246-L255.View ArticlePubMedGoogle Scholar
- Hayes JD, Flanagan JU, Jowsey IR: Glutathione transferases. Annu Rev Pharmacol Toxicol. 2005, 45: 51-88. 10.1146/annurev.pharmtox.45.120403.095857.View ArticlePubMedGoogle Scholar
- Kinnula VL, Crapo JD: Superoxide dismutases in the lung and human lung diseases. Am J Respir Crit Care Med. 2003, 167: 1600-1619. 10.1164/rccm.200212-1479SO.View ArticlePubMedGoogle Scholar
- Tourkina E, Gooz P, Oates JC, Ludwicka-Bradley A, Silver RM, Hoffman S: Curcumin-induced apoptosis in scleroderma lung fibroblasts: role of protein kinase cepsilon. Am J Respir Cell Mol Biol. 2004, 31: 28-35. 10.1165/rcmb.2003-0354OC.View ArticlePubMedGoogle Scholar
- Abrahamson M, Alvarez-Fernandez M, Nathanson CM: Cystatins. Biochem Soc Symp. 2003, 70: 179-199.View ArticlePubMedGoogle Scholar
- Dickinson DP: Cysteine peptidases of mammals: their biological roles and potential effects in the oral cavity and other tissues in health and disease. Crit Rev Oral Biol Med. 2002, 13: 238-275.View ArticlePubMedGoogle Scholar
- Kato T, Imatani T, Miura T, Minaguchi K, Saitoh E, Okuda K: Cytokine-inducing activity of family 2 cystatins. Biol Chem. 2000, 381: 1143-1147. 10.1515/BC.2000.141.View ArticlePubMedGoogle Scholar
- Kato T, Ito T, Imatani T, Minaguchi K, Saitoh E, Okuda K: Cystatin SA, a cysteine proteinase inhibitor, induces interferon-γ expression in CD4-positive T cells. Biol Chem. 2004, 385: 419-422. 10.1515/BC.2004.047.View ArticlePubMedGoogle Scholar
- Zavasnik-Bergant T, Repnik U, Schweiger A, Romih R, Jeras M, Turk V, Kos J: Differentiation- and maturation-dependent content, localization, and secretion of cystatin C in human dendritic cells. J Leukoc Biol. 2005, 78: 122-134. 10.1189/jlb.0804451.View ArticlePubMedGoogle Scholar
- Gabay C, Kushner I: Acute-phase proteins and other systemic responses to inflammation. N Engl J Med. 1999, 340: 448-454. 10.1056/NEJM199902113400607.View ArticlePubMedGoogle Scholar
- Honore B, Vorum H: The CREC family, a novel family of multiple EF-hand, low-affinity Ca2+-binding proteins localised to the secretory pathway of mammalian cells. FEBS Lett. 2000, 466: 11-18. 10.1016/S0014-5793(99)01780-9.View ArticlePubMedGoogle Scholar
- Vorum H, Hager H, Christensen BM, Nielsen S, Honore B: Human calumenin localizes to the secretory pathway and is secreted to the medium. Exp Cell Res. 1999, 248: 473-481. 10.1006/excr.1999.4431.View ArticlePubMedGoogle Scholar
- Basrur V, Yang F, Kushimoto T, Higashimoto Y, Yasumoto K, Valencia J, Muller J, Vieira WD, Watabe H, Shabanowitz J, et al: Proteomic analysis of early melanosomes: identification of novel melanosomal proteins. J Proteome Res. 2003, 2: 69-79. 10.1021/pr025562r.View ArticlePubMedGoogle Scholar
- Vorum H, Jacobsen C, Honore B: Calumenin interacts with serum amyloid P component. FEBS Lett. 2000, 465: 129-134. 10.1016/S0014-5793(99)01734-2.View ArticlePubMedGoogle Scholar
- Coppinger JA, Cagney G, Toomey S, Kislinger T, Belton O, McRedmond JP, Cahill DJ, Emili A, Fitzgerald DJ, Maguire PB: Characterization of the proteins released from activated platelets leads to localization of novel platelet proteins in human atherosclerotic lesions. Blood. 2004, 103: 2096-2104. 10.1182/blood-2003-08-2804.View ArticlePubMedGoogle Scholar
- Chardin P, Paris S, Antonny B, Robineau S, Beraud-Dufour S, Jackson CL, Chabre M: A human exchange factor for ARF contains Sec7- and pleckstrin-homology domains. Nature. 1996, 384: 481-484. 10.1038/384481a0.View ArticlePubMedGoogle Scholar
- Venkateswarlu K: Interaction protein for cytohesin exchange factors 1 (IPCEF1) binds cytohesin 2 and modifies its activity. J Biol Chem. 2003, 278: 43460-43469. 10.1074/jbc.M304078200.View ArticlePubMedGoogle Scholar
- Theis MG, Knorre A, Kellersch B, Moelleken J, Wieland F, Kolanus W, Famulok M: Discriminatory aptamer reveals serum response element transcription regulated by cytohesin-2. Proc Natl Acad Sci USA. 2004, 101: 11221-11226. 10.1073/pnas.0402901101.PubMed CentralView ArticlePubMedGoogle Scholar
- Ryckman C, Vandal K, Rouleau P, Talbot M, Tessier PA: Proinflammatory activities of S100: proteins S100A8, S100A9, and S100A8/A9 induce neutrophil chemotaxis and adhesion. J Immunol. 2003, 170: 3233-3242.View ArticlePubMedGoogle Scholar
- Ahmad A, Bayley DL, He S, Stockley RA: Myeloid related protein-8/14 stimulates interleukin-8 production in airway epithelial cells. Am J Respir Cell Mol Biol. 2003, 29: 523-530. 10.1165/rcmb.2002-0286OC.View ArticlePubMedGoogle Scholar
- Viemann D, Strey A, Janning A, Jurk K, Klimmek K, Vogl T, Hirono K, Ichida F, Foell D, Kehrel B, et al: Myeloid-related proteins 8 and 14 induce a specific inflammatory response in human microvascular endothelial cells. Blood. 2005, 105: 2955-2962. 10.1182/blood-2004-07-2520.View ArticlePubMedGoogle Scholar
- Vogl T, Ludwig S, Goebeler M, Strey A, Thorey IS, Reichelt R, Foell D, Gerke V, Manitz MP, Nacken W, et al: MRP8 and MRP14 control microtubule reorganization during transendothelial migration of phagocytes. Blood. 2004, 104: 4260-4268. 10.1182/blood-2004-02-0446.View ArticlePubMedGoogle Scholar
- Shibata F, Miyama K, Shinoda F, Mizumoto J, Takano K, Nakagawa H: Fibroblast growth-stimulating activity of S100A9 (MRP-14). Eur J Biochem. 2004, 271: 2137-2143. 10.1111/j.1432-1033.2004.04129.x.View ArticlePubMedGoogle Scholar
- Zhang H, Meng LH, Zimonjic DB, Popescu NC, Pommier Y: Thirteen-exon-motif segnature for vertebrate nuclear and mitochondrial type IB topoisomerases. Nucleic Acids Res. 2004, 32: 2087-2092. 10.1093/nar/gkh525.PubMed CentralView ArticlePubMedGoogle Scholar
- Steen VD, Powell DL, Medsger TA: Clinical correlations and prognosis based on serum autoantibodies in patients with systemic sclerosis. Arthritis Rheum. 1988, 31: 196-203.View ArticlePubMedGoogle Scholar
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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trade show in tokyo download free Nb7x full file
== Search results for trade show in tokyo ==
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use the following search parameters to narrow your results:
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Tropical Fish Keeping - Aquarium fish care and resources (http://www.tropicalfishkeeping.com/forum.php)
- Beginner Freshwater Aquarium (http://www.tropicalfishkeeping.com/beginner-freshwater-aquarium/)
- - Need help identifying Cory (http://www.tropicalfishkeeping.com/beginner-freshwater-aquarium/need-help-identifying-cory-55280/)
Need help identifying Cory
I went through the fish profiles and narrowed it down to three possibles.
-Reticulated Cory
-Julii Cory
-Three Stripe Cory
Any thoughts which of the three it might be? Also, how do I sex a cory?
If I place this fish in with my breeding albino corys, will it crossbreed with them? I will try and snag a clearer picture of the fish a bit later, its a bit camera shy.
t looks to me like a Julli Cory..
I don't think it is a Julii. These corydoras are pretty rare and are typicaly spotted.
Looks like a three stripe/leopard corydoras to me. The Tropical Fish Profiles (top left of this page) can fill you in on how to take care of them.:-D
Not to hard to get it really does look like a julli cory..
Google Image Result for http://app.onlinephotofiler.com/images/A_1/6/5/1/91561/Julii_Cory_d4477.1600x1200.jpg
Apologies, I guess they are Juliis. Maybe I spelled it wrong?
Nice job thefishboy!:-D
Lol never new i would eventually be naming what type of species lol!!
I was thinking of getting them so studied them alot lol...
thats my favorite cory! i have one in my tank, i need to get her (i call it a her cause juli sounds female lol) some more friends.
Yes defo get ome more 3 would be ok but a group of 6 in total would be realy good, more fun behaviour...:-)
Yeah I keep trying but my local shops always have ones that look sick or unhealthy :( I've tried multiple times with their jullis but they all just die off. This one I have was the healthiest and I got her and she lived.
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Company Profile
Guangzhou aminy footwear Co., Ltd. is a manufacturer, wholesaler and exporter of all types of shoes like lady leather shoes, sandals, boots and all kinds of women's shoes. We are a professional manufactory that integrating the development, manufacture and trading of medium and high class of ladies shoes as a unit, it owns several advanced production lines, advanced shoe-making equipment and top management team, occupied an area of 6000 sqm, currently there are about 300 employees including all the staff and management team, our products are pure handcraft work, all the products need to pass ...
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text:
By the way, the reason they always use bat, doc, exe, and pif(IF YOU SEE
THESE EXTENSIONS BE SUSPICIOUS IMMEDIATELY) is these files carry
instructions that the computer executes automatically when you click on
them, other files like jpg, txt, and others don't run automatically or
at all for that matter, they aren't computer instruction files. Bat is
an old text file of instructions like autoexec.bat which runs when your
computer boots up, doc text files can have visual basic language macro
instructions so are especially good if you use microsoft products to
spread the virus in your computer, exe is compiled binary files, and I
am not all that familiar with pif(Program Information File) files but
they seem to work just as well at infecting. Another one I can think of
right now is scr which is a screen saver file(one type) but can carry
computer instructions. All these files carry instructions that the
computer runs automatically and does things like over write files,
change file extensions to confuse the computer(if it looks for a certain
file and the extension has been changed it won't run), rename things,
mess with email accounts by going to the address book and sending emails
to everyone along with the virus.
Bob Bob Axmear 208 2nd St Ne Waukon, Ia 52172
Hostasonline http://hostasonline.com/
Gardensights Websites http://gardensights.com/
Hosta Library http://hostalibrary.org/
To sign-off this list, send email to email@example.com with the
message text UNSUBSCRIBE HOSTA-OPEN


text:
The Monthly GNU Column
This column looks into projects and current affairs in the world of free software from the perspective of the GNU Project and the FSF. In this issue, we take a look behind the drapes at the FSFE Annual General Meeting.
Welcome to a special issue of Brave GNU World focusing on the Free Software Foundation Europe (FSFE). The fourth Annual General Meeting of the FSFE took place in Vienna at the beginning of May 2005. This meeting was quite special in many ways. Not only was this the first full meeting of the European core team of the organization; it also marked the end of the European Executive's term of office. The European spin-off has now been around for four years – high time to look back at the highlights, polish the crystal ball, and peer into the future. Battle against Software Patents The focus of the FSFE's work continues to be the battle against the patentability of algorithms. There have been various activities at various levels. The patent battle also influences the case of Microsoft versus the European Commission.
Buy this article as PDF
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Read full article as PDF:Brave_GNU_World.pdf (129.63 kB)
Munich Plans to Ditch Linux and Go Back to Windows
A major setback for the Linux desktop.
Linux Kernel 4.10 Comes with New Security Features
Improved support for GPU in virtualization.
OpenSUSE Site Hacked
News site for the openSUSE community falls victim to a Wordpress exploit.
LibreOffice Goes Online with 5.3 Release
The source code is available online.
Microsoft Brings Clear Linux OS to Azure
One out of three virtual machines on Microsoft Azure Cloud run Linux.
ASUS Announces a Single-Board Computer
The form factor of the board makes it a drop-in replacement for Raspberry Pi.
Red Hat Releases RHEL 6.9 Beta
Makes it easier for customers to move workloads into container-centric applications.
SUSE Working on a New Operating System Called MicroOS
SUSE's answer to container-centric operating systems.
Biggest Kernel Release Ever
Linux 4.9 is the biggest release in terms of number of commits.
CentOS Linux 7 (1611) Released
The latest version of the official RHEL clone is here.


text:
Hotel Murakami
No prices found through our partners. Please contact the business directly or check some of our recommended alternatives.
- Smoking rooms available
- Wireless internet connection in public areas
- Breakfast Available
- Wireless internet connection in room (free)
- High-speed internet in room (free)
- High-speed internet in room
Photos of Hotel Murakami
Travelers also looked at:
- Non-smoking rooms
- Smoking rooms available
- Wireless internet connection in public areas
- Breakfast Available
- Wireless internet connection in room (free)
- High-speed internet in room (free)
- High-speed internet in room
- Air-Conditioning
- Free parking
- Laundry facilities (self serve)
- Meal plan
TripAdvisor Reviews Hotel Murakami Nikko
Travel Blogs from Nikko
... any post office on departure.
Last but by no means least the people. Japanese are the most polite, courteous, helpful and generous people. Bowing - again we could write a book on it, but it is a sign of appreciation and respect. Bowing as you leave the hotel, enter the hotel, as the train conductor leaves the carriage, as the taxi ...
... War 2. The garden was serene and showing good autumn colours, though not yet at their peak.
A visit to Kirifuri waterfalls that involved a short walk along a quite uneven path with quite a few steps in poor light finished off the day before the long slow drive back to Tokyo. Part way we stopped at this "food court" type place that was very busy and oddly out of context with its surrounds. As we only had a short break ...
Never Say Kekko...
... s dollars. We walked up another set of stairs and through the Omote-mon, a gate protected by two red devils. To the right and directly ahead stood three sacred storerooms filled with swords, bows and arrows and other battle gear. On the left sits the sacred stable adorned with intricate monkey carvings as monkeys are believed to be protectors of horses. A bonsai tree exhibit decorated the sides of the path as we continued towards the main shrine complex. Walking under another set ...
One last ride, best tempura and final thoughts
... to what you get in Vancouver Japanese restaurants but the quality was outstanding. Amy was right when she said that tempura in Japan is far superior to what you get in Vancouver which is usually heavy, thick, oily batter on your prawn and vegetables. This was light, crisp and not oily at all. And the tempura prawns were the best I've ever had. I don't know what kind of prawn it was but it almost tasted like lobster. I've got to come back here with Amy and Wesley too. What a ...
Drizzly day but hooray for red bean pastries!
It was a drizzly day when I got up this morning so I waited for the drizzle to ease up and went for a short ride. I stopped at the site of Japan's oldest university, the Ashikaga School, which was founded in the 1400's. I toured the grounds for about 30 minutes before continuing on my way. I barely got out of the city into the countryside when the drizzle started up again so I decided to turn back.
On the way, I ...


text:
More Videos...
World's First TWIN TURBO Huracan! 2100hp!
Less than a year ago Lamborghini released the replacement for the Gallardo... With some major styling, engine & transmissions changes, the Huracan promises a SOLID platform for our friends at Underground Racing to build a beast... and they ALREADY have a 2100hp twin turbo Huracan that touched down at Texas Invitational! Not only did they strap on the X package twin turbo kit making 2100hp but ALSO adding a sequential transmission system & rolling antilog to jump out of the gate hard. This car is absolutely gorgeous and we were excited to see this beast go rounds at the Spring Texas Invitational event! --------------------------------------------------------------------------- --------------------------------- 1320Video Gear ► http://www.1320video.com/shop/ Facebook ► http://facebook.com/1320videos Instagram ► https://instagram.com/1320video/ Twitter ► https://twitter.com/1320video Submit your video to us ►http://goo.gl/forms/TbQPwl9qFq
340 km/h en Ferrari 430 Scuderia NovitecRosso (Option Auto)
Version HD : https://www.youtube.com/watch?v=4iddJ8YHtUU F430 Scuderia Bi Compresseur de 717 ch ! - ON ROAD SPEEDO / NOT A SINGLE Dyno TEST ON OPTION AUTO VIDEOS - www.optionauto.com -
Twin Turbo Lamborghini Gallardo Superleggera Dyno - 1042RWHP
Facebook: http://on.fb.me/RHPage Twitter: http://bit.ly/RHTweets (MORE...) PHOTOS OF THIS CAR: http://razzi.me/albums/141-sprite-s-twin-turbo-lamborghini-gallardo-superleggera A twin turbo Lamborghini Gallardo Superleggera on Dyno at Heffner Performance. TT SL. This is not an Underground Racing car. Temperature = 105* Humidity = 20%
Twin Turbo Ferrari Testarossa on Engine Dyno
Twin turbo Ferrari Testarossa on Engine Dyno. The motor is a 4.9L flat 12 which has been upgraded with EFI via a Bigstuff3 PRO SEFI ECM and twin Precision turbo turbochargers. At this stage the motor is running 6psi Boost and has no internal modifications. We ran it from 3500rpm to 7500rpm and it produced 650hp and 600lbs*ft of torque. Enjoy! Also I just posted a new video on my channel showing a walk around of the car with some of the new wheels and brakes mocked up on it. If you guys are interested check it out there.


text:
Dr. Matthew Holtmeier, Postdoctoral Teaching Fellow in Screen Studies, recently presented at the annual Society for Cinema and Media Studies (SCMS) conference in Montreal, Canada.
Participating in a workshop titled 'Teaching Transnational Cinemas,' he discussed how to enact a critical pedagogy through assignment and curriculum design, and best practices for contextualizing transnational media. This panel was selected by the SCMS Transnational Cinemas Scholarly Interest Group as having particular significance to the academic study of transnational media.
Andrew Utterson (Communications) presents at annual Society for Cinema and Media Studies (SCMS) conference
Dr. Andrew Utterson, Assistant Professor of Screen Studies, recently presented at the annual Society for Cinema and Media Studies (SCMS) conference in Montreal, Canada.
Participating in a panel on the role of sound in online and app-based documentary projects (including a recent work by Canadian artist Stan Douglas), he spoke about theories of interactivity and immersion in considering the role of online and mobile screen technology in mediating our auditory experiences of the world, including how sound (unrecorded as well as recorded) shapes our experiences and understanding of space and place.
This panel was selected by the SCMS Documentary Studies Scholarly Interest Group as having particular significance to the academic study of documentary.
Diagnosis causes Park School associate dean to get into advocacy, outreach, and research trials.
Actor and philanthropist Geena Davis will serve as this year's Park Distinguished Visitor. One of Hollywood's most respected actors, Davis will speak on "Gender Equality in The Modern Media" on March 31 at 8 p.m. in Ford Hall, Whalen School of Music. The lecture is free and open to the public.
NOTE: Limited seating is available. The event will also be live streamed in Textor 102 and online at: http://www.livestream.com/parkmedianetwork. Doors will open approximately 30 minutes before the event. Students enrolled in the Media for Social Responsibility course will be seated ahead of time, as this lecture is part of their course hours.
About Geena Davis:
Davis broke ground in her portrayal of the first female President of the United States in ABC's hit show Commander in Chief, earning the 2006 Golden Globe Award for Best Performance by an Actress in a Television Series – Drama. She currently plays Dr. Nicole Herman on Grey's Anatomy.
My Antigua, An Island Revealed, edited and designed by Professor Janice Levy, was recently published.
The 300-page book consists of photographs, poetry, and prose by thirteen "at risk" students who participated in a two-week intensive photographic workshop Levy taught in January 2014 at GATE (Government Assisted Technology Endevour). Four months later, Levy returned to Antigua with writing instructor and publisher Robert Colley of Standing Stone Books, who inspired the students to write pieces related to their life and work.


text:
Dimebag Darrell 19662004
It's devastating, yet oddly poetic, that 38-year-old heavy-metal guitar god Dimebag Darrell (ex-Pantera) literally died onstage. On December 8 in Columbus, Ohio, just seconds after the seminal shredder's new band, Damageplan, started their first song, a 25-year-old gunmanallegedly seeking revenge for Dimebag breaking up Panterajumped onstage, repeatedly shot Darrell point-blank, then turned on the audience, killing three others. Dimebag (born Darrell Abbott) was idolized in the metal community, where his genius was acknowledged as ranking with that of Randy Rhoads and Eddie Van Halen. Pantera's dissonant, pot-fueled, power-groove riffs completely reshaped the template of modern metal, and the band's cult-like statuswhich, over the course of five studio albums, grew into auditorium-sized popularitywas hugely responsible for metal's comeback after its late-'80searly-'90s stranglehold by grunge and alternative. A self-proclaimed advocate of THC, tittie barshe owned one in his home state of Texasand, of course, titanium-plated music, Dimebag always came off more like a fan than a rock star. He'd gush about his heroes, Judas Priest and Kiss, and he constantly supported up-and-coming acts. As the lyrics from Pantera's final hit, the hesher anthem "Goddamn Electric," affirm, the dude lived it: "Your trust is in whiskey and weed and Black Sabbath." He was goddamn electric.
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The New Southern-Latino Table, Recipes That Bring Together the Bold and Beloved Flavors of Latin America and the American South by Sandra A. Gutierrez includes recipes like Green Mango Salad with Pepita and Benne-Dusted Shrimp; Albóndigas with Sweet Fire-Roasted Tomato Chutney; and Rolled Ham Salad Cake (Pionono).
Serves 4
Green mango salad with lime, salt, and dried chile is a very popular street food in Mexico and Central America. This citrusy salad, scented with cumin, coriander, and mint, is refreshing and strikingly colorful. Here, I coat plump shrimp with a ground mixture of nutty seeds. Benne is the African word for sesame seeds. Europeans introduced them to Latin America (where they're known as ajonjoli), and African slaves brought them to the South. The ingredient list is long here, but the steps are easy. Choose large, firm mangoes that are not too ripe; they should not give when pressed. The smaller, green mangoes sold in Asian stores will also work. Use a serrated potato peeler to remove their skins easily. This recipe doubles and triples perfectly, making it ideal for larger crowds. Pucker up!
For the Dressing
For the Shrimp
In a large bowl, toss together the mango, carrots, onions, cilantro, and jalapeno; set aside. In a small bowl, whisk together the lime juice, oil, salt, cumin, pepper, chile powder, coriander, and mint. Toss the salad with the dressing; set aside for 20 minutes (or chill for up to 8 hours).
Grind the pumpkin and sesame seeds in a coffee grinder (or small food processor) until they're a fine powder, being careful not to form a paste; place in a small bowl and add the salt. In a large skillet, heat the oil over medium heat. Working in batches, dip the shrimp into the egg white and coat on both sides with the seed powder. Add to the skillet and saute for 2 minutes on each side, or until golden and crispy. Arrange the salad on 4 plates. Top each with the shrimp and serve.
Note: To toast sesame seeds, place them in a dry skillet over low heat, stirring until they're fragrant and have begun to tum golden. Watch them carefully so they don't burn. Toasted sesame seeds are available in bulk in most Latin tiendas.
Buy The New Southern-Latino Table
This page created January 2012
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|Juha Laiho <Juha.La...@iki.fi>
|Re: Setting the Right Amount of Memory
|Sun, 20 Jun 2010 16:02:47 GMT
On 20.6.2010 14:06, Mark Thomas wrote: > On 20/06/2010 00:30, André Warnier wrote: >> Just a note here : 160 X 512 MB = 81 GB. >> If each Tomcat's JVM is allowed to use up to 512 MB of Heap, there might >> be moments where a lot of JVM's will be using close to that amount. >> Unless your system can really support that amount of real RAM, you may >> be in for massive swapping. > > And that could be a major problem. JVMs and swapping do not place nicely > together. To quote some folks at work that have been looking at this > recently performance "falls of a cliff". Yep, I've seen that as well -- and the effect really is easy to understand, esp. in the light of how Chuck explained the mark-sweep-compact memory management. The live objects are somewhat scattered throughout the heap, and walking through the live object graph will touch all of them -- thus if any was paged out at the moment, it will be paged in (most likely forcing some other page out). If majority of the OS-level virtual memory consumption consists of JVM heaps, then it's very likely that the paged-out memory page does contain a live Java object - which will again be paged in when the owning JVM does its "mark" phase. Paging is suitable OS-level memory management for processes with full pages of data that only needs to be accessed infrequently (or perhaps only in the initialization phase of the application). Then these seldom-accessed pages can be moved out to disk, freeing RAM for more frequently needed items. With JVM memory management, everything is accessed every now and then, making paging a real performance-killer. -- ..Juha --------------------------------------------------------------------- To unsubscribe, e-mail: email@example.com For additional commands, e-mail: email@example.com
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SEI Walnut Tumble Dye is not your Grandparents' tie dye. Tumble Dye is a non-toxic, water based, ready to use pigment dye that requires no gloves. It's permanent, washable and can be used and reused. No dunking, soaking and washing needed. Simply spray the article with the dye for the desired look, let the article air dry and then heat set the article (dryer for 20 minutes or with an iron) and wear. It's that easy!
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Dr. Kelly Miller has recently returned to Lawrence and joined her father, Dr. Les Miller, in the practice of general dentistry at Lawrence Dental Solutions, 545 Columbia Drive. The business provides a wide range of dental services ranging from preventive to cosmetics.
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Are you looking for Business Growth in OHIO? Hotfrog showcases more than 80 popular businesses related to Business Growth in OHIO! Find a specific region or suburb using the left navigation.
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Cleveland, OH
Since 1989, our business turnaround consultants have helped underperforming & distressed companies develop a business growth strategy to achieve continuous improvement & increased profitability
GROWTH STRATEGYSales Process ImprovementCrisis Management Planning
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Our life insurance agents have a wealth of experience and understand the differences between many of the offerings in the market
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The Holland Springfield Chamber of Commerce exists to promote business growth and enhance the quality of life in our community Click to view our newest members
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Pfingsten Partners, LLC was formed in 1989 as an operationally focused private equity firm which invests in middle market manufacturing, distribution and business service companies Since completing our first inv…
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We are tapping into the warehouses around the country to bring you wide range of computer products instead of stocking and selling very limited number of items The rapid business growth was helped by boom in th…
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We have set ourselves apart from the other IT based service providers through constant efforts and dedication towards our work In an IT enabled world we stand out as providers of extensively user friendly end t…
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It's time to take a short break from all the healthcare changes and focus on your December 1st and 15th deadlines for the following participant notices for calendar year retirement plans:
The annual safe harbor notice must be provided to all plan participants at least 30 days (and no more than 90 days) before the first day of the plan year. The Notice must include 2014 information about the employer's safe harbor contributions; certain plan provisions, such as the withdrawal and vesting provisions; and the deferral compensation limits. The 2014 limits can be found here.
If you wish to preserve the ability to reduce or suspend safe harbor non-elective employer contributions during the 2014 plan year for any reason, the Notice should state that the plan may be amended during the plan year and that such change will take effect at least 30 days after all eligible employees are notified of the reduction or suspension.
Annual Automatic Enrollment Notice – December 1, 2013
If your plan automatically enrolls participants, the Automatic Enrollment Notice must be provided at least 30 days (and no more than 90 days) before the first day of the plan year. The notice must describe the plan enrollment provisions and the amount that will be deducted from participants' pay automatically and contributed to the plan during 2014. A sample notice can be found at www.irs.gov/pub/irs-tege/sample_notice.pdf.
The QDIA notice is required if your plan allows participants to direct their own investments and automatically invests in a QDIA to the extent participants fail to provide direction. The Notice is required to provide certain information about the QDIA as well as the participant's right to transfer out of the QDIA into other plan investments and the procedures for making such transfers. For more information about QDIA notices go to http://www.dol.gov/ebsa/regs/fab2008-3.html
Defined contribution plans are required to provide the SAR. The SAR summarizes specific items from the plan's Form 5500 filing and should be provided to active participants as well as terminated participants who had account balances under the plan during the 2012 plan year. The December 15 deadline applies for calendar year plan participants that filed the 2012 Form 5500 under an October 15, 2013 extension.
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DISCLAIMER: Because of the generality of this update, the information provided herein may not be applicable in all situations and should not be acted upon without specific legal advice based on particular situations.
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text: The TCNJ Office of Post-Graduate Fellowships is hosting a "Life Hacking," two-part event with special guest, B. Cole. The event will take place on Friday, 11/18 and the entire TCNJ community is welcome to attend. Life Hacking for Students There is power in the collective. It is important to understand the tools that will… Continue Reading


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|OSU-03012 (AR-12)Potent PDK1 inhibitor
Sample solution is provided at 25 µL, 10mM.
Publications citing ApexBio Products
Related Compound Libraries
Quality Control
Quality Control & MSDS
- View current batch:
Purity = 98.00%
- COA (Certificate Of Analysis)
- MSDS (Material Safety Data Sheet)
- Datasheet
Chemical structure
Biological Activity
|OSU-03012 is potent inhibitor of recombinant PDK-1 with IC50 value of 5 μM.
|recombinant PDK-1
|5 μM
Chemical Properties
|Cas No.
|Download SDF
|Chemical Name
|Canonical SMILES
|Soluble in DMSO > 10 mM
|Store at -20°C
|General tips
|For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months.
|Shipping Condition
|Evaluation sample solution : ship with blue ice
All other available size: ship with RT , or blue ice upon request
OSU-03012 (AR-12) is an inhibitor of 3-phosphoinositide-dependent kinase-1 (PDK-1) with IC50 value of 5μm, which shows 2-fold higher potency over OSU-02067 [1].
OSU-03012 has represented to suppress PC-3 cell proliferation and induce apoptosis in PC-3 cells. Expression of the constitutively active forms of PDK-1 and Akt has revealed to reduce OSU-03012-induced apoptosis in PC-3 cell [1].
OSU-03012 could potently inhibit the growth of primary human VS cells and malignant schwannoma HMS-97 cells in a dose-dependent manner. In contrast, normal human Schwann cells showed to be more resistant to OSU-03012. Additionally, OSU-03012 revealed to inhibit phosphorylation of AKT at the threonine-308 site in both VS cells and HMS-97 cells [2].
[1] Zhu J1, Huang JW, Tseng PH, Yang YT, Fowble J, Shiau CW, Shaw YJ, Kulp SK, Chen CS. From the cyclooxygenase-2 inhibitor celecoxib to a novel class of 3-phosphoinositide-dependent protein kinase-1 inhibitors. Cancer Res. 2004 Jun 15;64(12):4309-18.
[2] Lee TX1, Packer MD, Huang J, Akhmametyeva EM, Kulp SK, Chen CS, Giovannini M, Jacob A, Welling DB, Chang LS. Growth inhibitory and anti-tumour activities of OSU-03012, a novel PDK-1 inhibitor, on vestibular schwannoma and malignant schwannoma cells. Eur J Cancer. 2009 Jun;45(9):1709-20.


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Milano (MI) Italy
Raul Barbieri was born in Milan in 1946. After having taken his degree in Architecture at Milan's Polytechnic, he started to work initially as a professional associate; in 1989 he founded his own practice in Milan which specialise [...]
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He took a degree in Architecture at Milans Polytechnic, then applied his skills specifically to residential planning.
The phenomenon [...]
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More Videos...
Power Commander Accessories: Quickshifter Types
In this video we introduce and describe the various types of Quickshifter shift sensor/switches that we have available. Generally, we list the appropriate shift sensor/switch on our website for your bike model and for an otherwise stock shift linkage. However when using aftermarket rearsets and/or changing your shift pattern to GP (reversed) shifting, you'll most likely need something different. This video should help you decide specifically what is appropriate for your specific bike.
2009 CBR1000RR w PowerCommander quickshift.
Testing timing on quickshift...
CBR1000rr HM GP Quickshifter - through the box
Jizz Machine stickers here: http://jizzmachine.com/shop/ Having a play on the bench with the new HM Quickshifter 'GP'. This is one very clever bit of kit which i can't wait to test on circuit... Its pretty much a seamless shifter now. Amazeballs. I normally have a HM+ shifter on here and this is just testing the GP, hopefully will get to test on circuit in December. Oh, and sorry but please don't expect me to respond to comments as sadly Google+ has made it impossible. Shame as i really enjoyed the comments. HM Shifter site here: https://www.hmquickshifter.com/produc... This is my '11 blade which i crashed a couple of months ago and since then she's been getting some tasty replacement parts.. more info coming soon :) Thank you again for everyone who helped me with the re-build of this bike via sticker purchases. I cannot thank you enough.
Motorcycle Accident DRIFTING Crash On Highway Honda CBR1000RR Drift Gymkhana Bike Drifts Video 2014
INSANE Motorcycle Accident Video 2014. Motorcycle drifting at high speeds on the highway crashes. Watch stunt rider on Honda CBR1000RR street bike performing drifts between and around cars a crossed multiple lanes of traffic on I-70 highway. The motorcyclist holds throttle wide open while spinning the rear tire leaving a trail of smoke behind on the freeway. The motorcycle crash was caused by drift stunt gone wrong that ends in epic fail. The video was filmed on I-70 a large public highway that runs through Saint Louis, Missouri area. The make and model of the stunt bike seen crashing is 2013 Honda CBR1000RR Fireblade 1000cc liter bike. Luckily the rider featured wrecking in this video was not seriously injured as a result of the crash. Amazingly the sport bike rider was able to get up and hitch a ride with another biker immediately after the accident. However his motorcycle was not as lucky. After the accident the motorcycle was not ride able. This video serves as a great reminder to all motorcycle riders to always wear proper protective gear such as full face helmet, leather jacket or padded nylon jacket, long pants, and gloves because no matter your skill level or the type of riding your doing you got to remember if your on two wheels soon then later your going to crash and may not be as lucky as the motorcycle stunt rider shown crashing in this video. Please SHARE & LIKE Video!!! SUBSCRIBE Blox Starz TV For NEW Videos http://www.youtube.com/subscription_center?add_user=bloxstarzlifestyle SUBSCRIBE Sitdown Steve Channel http://www.youtube.com/subscription_center?add_user=sitdownsteve Visit Blox Starz Official Web Site http://bloxstarzlifestyle.com Visit Streetfighterz Official Web Site http://streetfighterz.com CONNECT With Blox Starz Instagram: http://instagram.com/bloxstarz Facebook: http://facebook.com/bloxstarz Twitter: http://twitter.com/bloxstarz Google+: http://google.com/+bloxstarzlifestyle


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Are you looking for collection agency in BRITISH COLUMBIA? Hotfrog showcases more than 60 popular businesses related to collection agency in BRITISH COLUMBIA! Find a specific region or suburb using the left navigation.
Victoria, BC
and available as a trial download
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- 10-02-2011
Credit Recovery Centre is a full service Collection Agency providing effective, professional debt recovery assistance
Debt Recovery Credit RecoveryTracing
Surrey, BC
Western Credit Control is a Licensed and Bonded Collection Agency in the Province of British Columbia since 1991
Debt Collection
Kelowna, BC
Sudden Seizure Bailiff Services Inc serves Kelowna, British Columbia Sudden Seizure Bailiff Services Inc: Collection Agencies for Kelowna Sudden Seizure Bailiff Services Inc serving Kelowna Map & Directi…
Vancouver, BC
Debt Collection Agency, Vanco Recovery Services, is a highly effective debt collection and debt recovery service. Based in Vancouver, Canada its professional staff ensure that the most difficult of debts are rapidly and …
Debt Recovery Debt Collectionskip tracing
Richmond, BC
Our goal, as a collection agency, is to be recognized by our clients as the best in terms of quality, service and value
Debt Recovery Debt CollectorsDebt Collection
Debt Recovery Debt CollectorsDebt CollectionAccounts Receivable
Abbotsford, BC
International Credit Assistance offers Collections, Consultants, Legal Assistance and loans. Consulting with debtors and full collection services for our clients is available
Vernon, BC
Credit Bureau of Vernon Ltd helps individuals, small businesses & large corporations recover delinquent accounts. We follow a "no collection – no fee" policy
Debt Recovery Debt CollectionCredit Bureau
Campbell River, BC
Coast Bailiff & Collections has been a recognized business on Vancouver Island for 15 years providing the following services: Bailiff * Collections * Process Serving * Skip Tracing * Tenancy and Occupancy Checks * I…
Debt Recovery Debt Collectionskip tracingBailiff
Advanced Collection Services Ltd. is a collection agency based in Victoria, BC which offers personalized service, or you can use our online listing sheets
Debt CollectionDebtorsskip tracingskip
Dyanne has joined Karma Publications' Directories & Resource Guide in 2011 and 2012 as our Client Care Specialist in order to help you with your business needs and services
Revelstoke, BC
Laurus Financial provides professional debt collection services for residential and industrial trade contracting companies. Laurus Financial's debt collection services can make an immediate improvement in your company's …
Debt Recovery Debt CollectionAccounts Receivable
Burnaby, BC
As one of the top agencies in British Columbia, our Collection Departments success has been due to our collection expertise, diligence and customer service
Debt CollectionDebtorsskip tracingCollection Software
Langley, BC
SAG Debt Consulting Inc. is a company designed to facilitate our clients in managing their accounts receivables
Professional Debt Recovery Services, Credex has been providing innovative solutions and exceptional results for our clients since 1991
Debt Recovery Accounts Receivable ManagementCollection Systems
Westbank, BC
Powell River, BC
Coquitlam, BC
Williams Lake, BC
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