text:
The association among leukocyte apoptosis, autoantibodies and disease severity in systemic lupus erythematosus
Yu-Jih Su1,6,
Tien-Tsai Cheng1,
Chung-Jen Chen1,
Wen-Chan Chiu1,
Chung-Yuan Hsu1,
Wen-Neng Chang2,
Nai-Wen Tsai2,
Chia-Te Kung3,
Hung-Chen Wang4,
Wei-Che Lin5,
Chih-Cheng Huang2,
Ya-Ting Chang2,
Chih-Min Su6,3,
Yi-Fang Chiang2,
Ben-Chung Cheng1,6,
Yu-Jun Lin6,4 &
Cheng-Hsien Lu2,6
Both apoptosis and autoantibodies are important factors associated with disease activity in the pathogenesis of systemic lupus erythematosus (SLE). This study tested the hypothesis that increased leukocyte apoptosis is associated with elevated levels of autoantibodies and the disease activity of SLE.
Leukocyte apoptosis was determined by flow cytometry, including annexin V, APO2.7, and 7-amino-actinomycin D (7-AAD) on each subtype of leukocyte in 23 patients with SLE. Leukocyte apoptosis was also evaluated in nine patients with Sjogren's syndrome (SJS) and in 20 volunteer subjects. Titers of common autoantibodies and the disease activity index (SLEDAI-2 k) of the SLE patients were also determined.
Except for annexin V and APO 2.7 of monocytes and late apoptosis (annexin V + 7-ADD) of lymphocytes, apoptosis in the total and in subsets of leukocytes were significantly higher in SLE patients than in controls (all p < 0.05, post hoc analysis). The mean percentage of late apoptosis of leukocytes (annexin V + 7-AAD) positively correlated with levels of anti-Ro52/60 (r = 0.513, p < 0.01), anti-La (r = 0.439, p = 0.04), and anti-Mi-2 (r = 0.492, p = 0.02), and inversely correlated with both C3 and C4 levels, although not statistically significant. The percentage of APO2.7 of CD19+ cells positively correlated with SLEDAI-2 K score (p = 0.01).
Leukocyte apoptosis is significantly higher in patients with SLE and correlates well with the levels of several autoantibodies. The APO2.7 of B-lymphocyte (CD19+) cells positively correlates with the disease activity of SLE.
Systemic lupus erythematosus (SLE) is a chronic systemic disease affecting mostly women of child-bearing age. It is the prototype of autoimmune diseases because of the variety of proposed pathogenesis. Dozens of autoantibodies are linked with SLE patients, including some that are diagnostic and specific [1–3], such as anti-double stranded deoxyribonucleic acid antibody (a-dsDNA), anti-Smith antibody (a-sm), and anti-ribosomal P (a-rib p). The disease activity of SLE has also been associated with these autoantibodies.
Apoptosis is one of several important mechanisms involved in the pathogenesis of SLE. A previous study has demonstrated that lymphocyte apoptosis is increased and removal of apoptotic cells is impaired in SLE. Furthermore, apoptosis is higher in active SLE compared to inactive SLE [4].
Several lines of evidence demonstrate the close relationship of apoptosis and autoantibodies. Delayed clearance of apoptotic residue, such as histone H3 [5], may result in the activation of antigen-presenting cells and the formation of autoantibodies [6, 7]. The antigenicity of autoantibodies is mostly against apoptotic cells, which has been demonstrated by Huggins et al. [8]. Most studies link lymphocyte apoptosis with titers of autoantibodies [9, 10], but little is mentioned regarding leukocyte apoptosis. The present study focuses on SLE patients due to this lack of detailed data.
To date, little is known about the relationship among leukocyte apoptosis, levels of autoantibodies, and severity of SLE. With the hypothesis that increased leukocyte apoptosis is associated with elevated levels of autoantibodies and disease activity of SLE, this prospectively-designed study aimed to report on the relationship among percentage of leukocyte apoptosis, levels of autoantibodies, and SLE disease activity.
Study patients
Twenty-three patients with definitive diagnosis of SLE and followed-up at the Rheumatology Out-patient Clinic for more than 6 months were prospectively evaluated. The diagnostic criteria for SLE were based on the 1997 revision of 1982 American College of Rheumatology (ACR) classification criteria for SLE [3], while the clinical assessment of disease activity of SLE was according to the SLE disease activity index (SLEDAI-2 K) [11]. For comparison, 20 age- and sex-matched healthy subjects year were enrolled as healthy controls and nine patients with Sjogren's syndrome (SJS) were the disease controls. The SJS patients were diagnosed based on classification criteria for SJS [12].
The Institutional Review Committee on Human Research approved the study protocol and the participants provided informed consent. Patients were excluded if they had autoimmune diseases other than SLE or SJS, or if they had fever or any infectious disorder that could affect the WBC count.
All of the subjects underwent complete medical examinations upon enrollment. Biomarkers were also collected. Since there were no clinical practice guidelines for SLE flare-up, the important decision in immuno-suppressant adjuvant treatment was whether or not to add a cytotoxic or corticosteroid-sparing drug like cyclophosphamide, methotrexate, azathioprine, mycophenolate mofetil, or leflunomide. Severe SLE was defined as an SLEDAI-2 K score >12, while mild-to-moderate SLE was an SLEDAI-2 K score ≤12 [13].
Blood sampling and assessment of leukocyte apoptosis
Blood samples were collected by venipuncture of the patient's forearm vein.
Flow cytometry assay using APO 2.7 Antibody for detecting apoptosis
All of the flow cytometry assays were performed within one hour after blood extraction to ensure that the results were as close as possible to the in vivo situation. Fixed amounts of blood were diluted 1:5 with PBS, and 100 μL was stained with 10 μL of each of the following: fluorescence conjugated monoclonal antibodies against CD45-phycoerythrin (PE)-Cy5 (clone J33), CD61-fluorescein isothiocyanate (FITC; clone SZ21), and APO 2.7-PE (clone 2.7A6A3; Immunotech, Marseille, France). These were then titrated at saturating concentrations.
The CD45-PE-Cy5 antibody reacted with the CD45 family of trans-membrane glycoproteins, expressed on the surface of all human leukocytes, and a pan-leukocyte marker. The CD61-FITC antibody was a pan-platelet marker that reacted with the GPIIb/IIIa complex (fibrinogen receptor). The APO 2.7-PE antibody reacted with a 38-kDa mitochondrial membrane protein (7A6 antigen), which was detectable on non-permeabilized cells in the late apoptotic state [14].
Annexin V staining, relevant to early apoptosis, produced similar results but was rejected for questionable reliability under fixation conditions, with formaldehyde clearly biasing the staining results. Mouse immunoglobulin G-PE was a control for non-specific staining, which did not differ from the APO2.7-PE signal on platelets, such that each subject was its own control without changing the sample tube. After 30 min of incubation in the dark at room temperature, the stained samples were diluted with 0.5 ml of FACSFlow (Becton Dickinson, San Jose, CA).
Flow cytometry analysis was performed immediately after staining using an Epics XL flow cytometer (Beckman Coulter, Fullerton, California) and the CellQuest software. Five thousand CD45-PE-Cy5+ cells per sample were acquired in a combined forward and side scatters and deep-red FL4 fluorescence (CD45-PE-Cy5) leukocyte gate. Another 5000 CD61-FITC + cells per sample were acquired in a combined forward and side scatters and green FL1 fluorescence (CD61-FITC) platelet gate to define a negative control threshold for the measurement of apoptosis, such that each subject was its own control.
Annexin V-FITC 7-AAD fluorescence-activated cell analysis
Membrane phosphatidyl-serine was detected by annexin-V using a commercially available kit (Boehringer Mannheim, Indianapolis, Indiana). The PBS-washed leucocytes were incubated with annexin V-FITC and 7-amino-actinomycin D (7-AAD) for 15 min at room temperature according to manufacturer's guidelines. Samples were transferred to 5-mL polypropylene tubes, diluted 900 μL with Hanks' balanced salt solution, and placed on ice before analysis by flow cytometry. The samples were analyzed using an Epics XL flow cytometer (Beckman Coulter, Fullerton, California) and the CellQuest software. Fifteen thousand events were counted per sample. Low-fluorescence debris was gated out of the analysis. Leukocyte subtypes were identified according to their CD45 expression intensity and divided into neutrophils, monocytes, and lymphocytes. From here on, white blood cells (WBC) represented total leukocytes.
Annexin V-FITC staining was identified in fluorescent-1 and 7-AAD staining in fluorescent-4. Cells were identified as follows: early apoptotic cells if they were positive for marker annexin V-FITC but negative for 7-AAD; late apoptotic cells if they were positive for annexin V-FITC and 7-AAD; dead cells if they were negative for annexin V-FITC but positive for 7-AAD; and viable cells if they were negative for annexin V-FITC and 7-AAD.
Apoptosis of lymphocytes
Fixed amounts of blood were diluted 1:5 with PBS and 100 μL was stained with 10 μL of each of the following: fluorescence conjugated monoclonal antibodies against CD4-phycoerythrin (PE)-Cy5, CD19-fluorescein isothiocyanate (FITC), and CD8- phycoerythrin (PE). Each of the above staining was further stained with annexin V-FITC, 7-amino-actinomycin D (7-AAD), or APO 2.7-PE (clone 2.7A6A3; Immunotech, Marseille, France). These were then titrated at saturating concentrations. Samples were transferred to 5-mL polypropylene tubes, diluted with 900 μL of Hanks' balanced salt solution, and placed on ice before flow cytometry. Samples were analyzed using an Epics XL flow cytometer (Beckman Coulter, Fullerton, California) and the CellQuest software. Fifteen thousand events were counted per sample. Lymphocyte subtypes were identified according to their surface antigen (i.e., CD4, CD8, or CD19) expression intensity. A database coordinator was responsible for monitoring all data collection and entry.
Autoantibody detection
Autoantibody titers, including IgG antibodies against dsDNA (a-dsdna), Ribosomal p (a-ribp), Ro (52/60) (a-ro), Ro 52 kDa (a-ro52), Ro 60 kDa (a-ro60), La (a-la), U1RNP (a-u1rnp), Sm (a-sm), and Mi-2 (a-mi2) were detected by Elia-Phadia 250 according to the operation manual. All data were checked for any inconsistencies. Intra-assay variability based on repeated measurements of the same blood sample was low, with mean coefficients of variance between 6.11% and 14.28% for SLE patients, and 6.0% in control individuals.
Data were expressed as mean ± SD or median (inter-quartile range). Categorical variables were compared using Chi-square test or Fisher's exact test, as appropriate. The percentage of leukocyte apoptosis and autoantibody level were logarithmically transformed to improve normality. Univariate analyses were compared using Student's t-test. Continuous variables among the three groups (SLE, SJS, and volunteer control) were compared using one-way ANOVA, followed by Bonferroni post hoc multiple comparison procedure. Correlation analysis was used to evaluate the relationship among mean SLEDAI-2 K score, percentage of leukocyte apoptosis, and levels of autoantibodies. Statistical significance was set at p < 0.05. Receiver operating characteristic (ROC) curves were generated for leukocyte apoptosis. The areas under the ROC curves (AUC) were calculated for each parameter and compared. All statistical calculations were performed using the SAS software package, version 9.1 (2002, SAS Statistical Institute, North Carolina).
Baseline characteristics of the study patients
The baseline characteristics and laboratory data of SLE patients, SJS patients, and control groups, as well as their medications, were listed in Table 1. Although the mean age was older in the SJS group, there was no statistically significant difference in age and sex among the three groups (p = 0.16 and p = 0.541, respectively). The clinical symptoms of the 23 SLE patients included musculo-skeletal involvement in 15, neurologic involvement in 14, muco-cutaneous involvement in two, hematologic involvement in six, cardio-respiratory involvement in two, and renal involvement in two. The clinical symptoms of the nine patients with SJS were also listed.
Table 1 Baseline characteristics of SLE patients, SJS patients, and control subjects
Leukocyte apoptosis in patients with SLE, patients with SJS, and the controls
The laboratory data and percentage of leukocyte apoptosis of the three groups were listed in Table 2. Except for hemoglobin level, the WBC and platelet counts were not significantly different among the three groups. Except for annexin V and APO2.7 in monocytes and annexin V + 7AAD in lymphocytes, the percentages of apoptosis of total leukocytes and the leukocyte subsets were significantly higher in the SLE patients than in the controls.
Table 2 Laboratory data of the SLE patients and control subjects
Correlation of clinical severity, autoantibody level, and percentage of leukocyte apoptosis
Regarding the innate immune cells, the mean percentages of late apoptosis of leukocyte (annexin V-FITC and 7-AAD) positively correlated with levels of anti-dsDNA (r = 0.415, p < 0.05), anti-Ro52/60 (r = 0.513, p < 0.01), anti-La (r = 0.439, p = 0.04), anti-Mi-2 (r = 0.492, p = 0.02), and inversely correlated with both C3 and C4 levels, although not statistically significant (Table 3). The SLE disease activity index (SLEDAI-2 K) positively correlated with anti-Ro 60 kDa (r = 0.407, p = 0.05), but negatively correlated with complement C4 level (r = -0.508, p = 0.01).
Table 3 Correlation among apoptotic markers, disease activity, and levels of autoantibodies in lupus patients
Regarding the adaptive immune cells, the percentage of CD4 (+) cell apoptosis in APO2.7 negatively correlated with anti-Ro 52 kDa (r = -0.717, p = 0.03), and anti-Ro52/60 (r = -0.684, p = 0.04). The percentage of CD19 (+) cell apoptosis in APO2.7 positive correlated with SLE disease activity index (SLEDAI-2 K) (r = 0.793, p = 0.01), but negative correlated with a-dsDNA (r = -0.883, p < 0.001). Furthermore, the AUC for the percentage of APO2.7 in B-lymphocyte (CD19+) apoptosis was 0.95 (p = 0.027, 95% CI: 0.00-1.00). The cut-off value of the percentage of APO2.7 in B-lymphocyte (CD19+) apoptosis for severe SLE was 1.01% (sensitivity 75% and specificity 95%). Other results were listed in Table 3.
The present study has several major findings. First, the percentage of leukocyte apoptosis (including neutrophil, monocyte, and lymphocyte apoptosis) is significantly higher in SLE patients than in healthy controls. Second, the mean percentages of late apoptosis of leukocyte (annexin V + 7-AAD) positively correlate with levels of most common autoantibodies (e.g. anti-Ro52/60, anti-La, and anti-Mi-2). Third, the percentage of CD4 (+) cell apoptosis in APO2.7 significantly but negatively correlates with levels of several autoantibodies (e.g. anti-Ro52/60, and anti-Ro52kDa). Fourth, the level of C3 negatively correlates with the late apoptosis of granulocyte (7-AAD + annexin V). The level of C4 positively correlates with the late apoptosis (7-AAD + annexin V) of CD8 cells. Lastly, the percentage of APO2.7 on B-lymphocyte (CD19+) apoptosis significantly correlates with median SLEDAI-2K score. The cut-off value of 1% of APO2.7 on B-lymphocyte (CD19+) apoptosis is associated with severe SLE. APO2.7 is expressed on the mitochondrial membrane during early apoptosis in relation to the release of cytochrome c and represents the activation-induced cell death under certain circumstances [15, 16].
Several lines of blood cells have defects in the apoptosis pathway in SLE patients, either prone or resistant to apoptosis [17–23]. Some studies reveal increased monocyte and lymphocyte apoptosis [18, 20, 21, 23], but other studies demonstrate increased leukocyte apoptosis [22], and decreased B-lymphocyte apoptosis [17] or no difference in apoptosis [19]. Generally speaking, in the present study, the percentages of apoptosis in most leukocyte subsets, including neutrophils, monocytes, and lymphocytes, are significantly higher in SLE patients than in controls.
Leukocyte late apoptosis markers are positively correlated with levels of several autoantibodies, including anti-Ro, anti-La, and anti-Mi2. This is an evident link between leukocyte apoptosis and antibody formation, as previously proposed [24, 25].
The CD4 (+) cell apoptosis marker APO2.7 is negatively correlated with levels of anti-Ro52, and anti-Ro. Since the anti- Ro antibody is elevated in many patients with lupus [26], CD4 (+) cell apoptosis may be decreased in SLE patients. The present study demonstrates that the APO2.7 of CD19+ lymphocytes is positively correlated with disease activity index. Several studies have demonstrated that the appearance of APO2.7 on lymphocytes represents activation and elevated titers of autoantibodies [16, 27]. However, activated APO2.7 on lymphocytes may be reversed by downstream anti-apoptosis molecules, as shown in other studies [15, 28]. Lastly, increased activated APO2.7 of CD19+ lymphocytes may undergo apoptosis after immuno-suppressant therapy [29]. Thus, in this study, activation through a mitochondria-dependent pathway among CD19+ lymphocytes is prominent in patients with active SLE. Disease activity is positively correlated with anti-Ro60 titers in this study, as previously mentioned in other investigations [1, 2].
During SLE flare-up, both C3 and C4 are decreased, so the late apoptosis of granulocyte increases [30] but the apoptosis of CD8 (+) cells decreases. The present study also demonstrates that the level of C3 is significantly but negatively correlated with the late apoptosis of granulocyte (7-AAD + annexin V), while the level of C4 is positively correlated with the late apoptosis (7-AAD + annexin V) of CD8 cells (Table 3). Linker-Israeli et al. have shown that CD8 (+) cells participate in autoantibody synthesis in SLE [31].
There are significant differences of apoptosis markers in annexin V of leukocytes (SLE vs. SJS, p = 0.029), neutrophils (SLE vs. SJS, p = 0.004), and monocytes (SLE vs. SJS, p = 0.036) during the post hoc analysis, despite no difference in absolute numbers of leukocytes, neutrophils, and monocytes between SLE and SJS patients. Similarly, Armstrong et al [22] demonstrated higher annexin V of neutrophils among SLE patients compared to those with other autoimmune diseases, while Bengtsson et al [21] demonstrated higher annexin V of monocytes. These finding suggest that there are more autoantigens, which may the induce apoptosis of leukocytes, in SLE patients than in the disease controls.
This study has several limitations. First, there are many assays for evaluating apoptosis in vitro so the results and interpretations from various methodologies may be partially different. The level of apoptosis tested by flow cytometry may not necessarily reflect the real leukocyte physiologic function in vivo. Similar protocols are used to detect cell apoptosis [29, 32, 33]. Second, this is a cross-sectional observational study. Theoretically, high-dose immuno-suppressant drugs can affect leukocyte activity and autoantibody levels. Although the dosages of steroids (mean, 31 mg/day) and hydroxychloroquine (mean, 300 mg/day) used in this case control study are not high, their effects still cannot be excluded. Lastly, the case number in this study is not large and similar aspects of results have been obtained from other series studies with small case numbers [34, 35]. Large-scale prospective and longitudinal studies are needed to evaluate the prognostic contribution of leukocyte apoptosis on clinical outcome.
In conclusion, leukocyte apoptosis is significantly higher in SLE patients and correlates well with the levels of several autoantibodies. The APO2.7 of B-lymphocyte (CD19+) cells positively correlates with the disease activity of SLE.
The study was approved by Chang Gung Memorial Hospital's Institutional Review Committee on Human Research.
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This work was supported by grants from Chang Gung Memorial Hospital (Chang Gung Medical Research Project CMRPG8B1281) and NHRI-EX101-10142EI. The authors thank all of the subjects who participated in this study and wish to thank Dr. Gene Alzona Nisperos for editing and reviewing the manuscript for English language considerations.
Departments of Internal Medicine, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan, China
Yu-Jih Su
, Tien-Tsai Cheng
, Chung-Jen Chen
, Wen-Chan Chiu
, Chung-Yuan Hsu
& Ben-Chung Cheng
Department of Neurology, Chang Gung Memorial Hospital, 123, Ta Pei Road, Niao Sung Hsiang, Kaohsiung, Taiwan, China
Wen-Neng Chang
, Nai-Wen Tsai
, Chih-Cheng Huang
, Ya-Ting Chang
, Yi-Fang Chiang
& Cheng-Hsien Lu
Emergency Medicine, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan, China
Chia-Te Kung
& Chih-Min Su
Neurosurgery, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan, China
Hung-Chen Wang
& Yu-Jun Lin
Radiology, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan, China
Wei-Che Lin
Department of Biological Science, National Sun Yat-Sen University, Kaohsiung, Taiwan, China
, Chih-Min Su
, Ben-Chung Cheng
, Yu-Jun Lin
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Correspondence to Cheng-Hsien Lu.
YJS participated in the study design and manuscript drafting. TTC, CJC, WCC, CYH, WNC, CTK, HCW, WCL, CCH, YTC, CMS, YFC, BCC, and YJL participated in the sequence alignment and clinical evaluation of patients. NWT performed the statistical analysis. CHL conceived the study, and participated in its design and coordination, and helped draft the manuscript. All authors read and approved the final manuscript.
Su, Y., Cheng, T., Chen, C. et al. The association among leukocyte apoptosis, autoantibodies and disease severity in systemic lupus erythematosus. J Transl Med 11, 261 (2013) doi:10.1186/1479-5876-11-261
Autoantibodies
Diseases severity score
Leukocyte apoptosis


text:
Sebastien La Ruelle (Chênée, 1591 - Luik, 16 april 1637) was burgemeester van Luik en aanvoerder van de partij van de Grignoux.

Biografie
Sébastien La Ruelle was afgestudeerd aan het Collège en Isle de Liège met de titel van doctor in de rechten. Hij werd in 1630 voor de eerste keer verkozen tot burgemeester van Luik op hetzelfde moment als zijn vriend Guillaume de Beeckman, die, volgens de geruchten, in opdracht van prins-bisschop Ferdinand van Beieren zou zijn vergiftigd en overleed op 29 januari 1631.

Op 16 april 1637 nodigde René van Renesse, ook René van Warfusée genoemd, Sébastien La Ruelle uit voor een banket in zijn privéwoning gelegen aan het huidige Xavier Neujeanplein. Dit banket bleek een hinderlaag te zijn en de voormalige burgemeester, die zeer gewaardeerd werd door de bevolking, werd door Spaanse soldaten - die zich hadden verscholen in het huis - vermoord. De aanwezigheid van deze soldaten in het huis van de graaf van Warfusée had de nieuwsgierigheid van een aantal burgers gewekt, die zich zorgen maakten over het lot van La Ruelle. Toen ze vernamen dat hij was gedood, beukten de in opstand komende burgers de deur van het huis van de graaf in en "de menigte stortte zich op hem als een meute, men verscheurde zijn kleren, men verbrijzelde hem onder hun voeten, men doorboorde zijn hiel, men haalde er een riem door, men sleurde hem door de straten in het stof waaruit hij modder maakte met zijn bloed ; men heest zijn lichaam op aan een galg opgetrokken aan de poort van de markt, vervolgens kapte men zijn hoofd en handen af, en men ging ze aan de verschillende poorten van de stad vastspijkeren; ten slotte verbrandde men zijn lichaam, en wierpen zijn as in de Maas".

Lichaam en begrafenis
De begrafenis van La Ruelle werd op 18 april 1637 gehouden. Zijn lichaam was opgebaard in de Sint-Lambertuskathedraal, waar het volk hem een laatste eer betuigde. De optocht voerde het lichaam van de burgemeester naar de Sint-Maartenkerk en Isle, waar hij werd begraven. Op 31 oktober 1798, toen de Luikse Revolutie volop woedde, werd het lichaam van La Ruelle opgegraven toen de Sint-Maartenkerk werd vernietigd.

Het lichaam van de burgemeester werd daarop naar het stadhuis overgebracht. Dr. Nicolas-Joseph Ansiaux, die aanwezig was bij de opgraving, neemt tijdelijk de doodskist van La Ruelle in bezit.

In 1827 was een apotheker uit de straat Chaussée des Prés in Outremeuse, Victor van Orle, in het bezit van de doodskist. Deze laatste gaf ze in 1850 terug aan het Institut archéologique liégeois waarvan een van haar leden, Félix Capitaine, zich zou bekommeren om de doodskist. Van 1857 tot 1909 werden de stoffelijke resten van de oud-burgemeester ondergebracht in een kapelletje belendend het paleis van de prins-bisschoppen. Van 1909 tot 1938 bevonden ze zich in het museum Grand Curtius.

In 1938 besloot de gemeenteraad unaniem om aan La Ruelle een grafmonument te schenken op het Xavier Neujeanplein. Maar de aanleg van een busstation zorgde ervoor dat er geen plaats meer was voor een graftombe voor La Ruelle. In 1957 werd zijn gebeente overgebracht naar een plaats in de buurt van de oude vleeshallen. Daar zouden ze blijven liggen totdat ze in de jaren 1990, tijdens de restauratie van het oude gebouw en haar aanhorigheden men hen nogmaals verhuist naar het lijkenhuis van de begraafplaats van Robermont.

In de loop van deze vele verhuizingen, zijn het hoofd en stukken van de ledematen van La Ruelle verloren gegaan. In 2007 vond een Luikse leraar op pensioen, Joseph Villez, de linkeronderarm terug in het bezit van een artsenfamilie en wist de eigenaar ervan te overtuigen de arm aan de stad Luik terug te geven.

Eerbewijzen
 Thomas Asselijn schreef met De Moort tot Luyk door den Graaf van Warfusé aan den Burgermeester de la Ruelle (1671) een toneelstuk over het tragische levenseinde van Sébastien La Ruelle.
 Sébastien Laruellestraat, een straat in Luik op de plaats waar de moord plaatsvond.

Noten

Referenties

 , Le banquet de Warfusée ou le meurtre de Sébastien La Ruelle, in Revue belge 3 (1836), pp. 181-200.
 , Impressions de voyage : Excursions sur les bords du Rhin, I, Den Haag, 1842.
 , Collection de documents contemporains relatifs au meurtre de Sébastien de La Ruelle, bourgmestre de Liège, Luik, 1868.
 , Testament du bourgmestre Sébastien La Ruelle, in Bulletin de l'institut archéologique liégeois 9 (1868), pp. 491–492.
 , Lettre sur l'assassinat de Sébastien La Ruelle adressée à M. D. Tome Van de Casteele, in Bulletin de l'institut archéologique liégeois 12 (1874), pp. 406–426.
 , Textes rares ou inédits concernant le bourgmestre La Ruelle, Luik, 1936.
 , Lettres curieuses concernant le meurtre du bourgmestre Laruelle, in Bulletin de la société royale Le Vieux-Liège 2 (1937), p. 196-198.
 , Testament du bourgmestre Sébastien Laruelle, in Bulletin de la société royale Le Vieux-Liège 2.41 (1937), p. 170.
 , L'iconographie de Laruelle, in Bulletin de la société royale Le Vieux-Liège 2.41 (1937), p. 170.
 , Laruelle et la peinture d'histoire, in Bulletin de la société royale Le Vieux-Liège 2.41 (1937), pp. 168–169.
 , Relation du meurtre fait en la personne de feu monsieur le bourgmestre de Laruelle, in Bulletin de la société royale Le Vieux-Liège 2.39 (1937), pp. 133–137.
 , Tri-centenaire de l'assassinat du bourgmestre Sébastien Laruelle, in Bulletin de la société royale Le Vieux-Liège 2.41 (1937), pp. 161–165.
 , Richelieu et Laruelle, in Bulletin de la société royale Le Vieux-Liège 2.41 (1937), pp. 166–167.
 , Un souvenir inconnu de Laruelle, in Bulletin de la société royale Le Vieux-Liège 2.44 (1937), pp. 215–216.

Vermoord Zuid-Nederlands politicus (voor 1830)
Burgemeester van Luik
Persoon in het prinsbisdom Luik
Persoon in de Nederlanden in de 17e eeuw

redpajama_set_name: RedPajamaWikipedia


The Allure End Table by Magnussen Home at HomeWorld Furniture in the Hawaii, Oahu, Hilo, Kona, Maui area. Product availability may vary. Contact us for the most current availability on this product.
The Allure collection is a great option if you are looking for Contemporary furniture in the Hawaii, Oahu, Hilo, Kona, Maui area.
Browse other items in the Allure collection from HomeWorld Furniture in the Hawaii, Oahu, Hilo, Kona, Maui area.


text:
Down 1st XI vs Campbellians 1st XI - 16th September 2006
Down's bid for Linden Cup glory is off to the worst possible start.
Against new-boys Campbellians at Malone Park last Saturday, Down played in fits and starts and never really got any rhythm going.
Last year, Down were unbeaten at home in the league and cup and ended up with the meanest defence in Senior Two. They will be hoping last weekend's performance was nothing more than an opening day blip and things will get better.
Two scrappy goals and an inability to kill off the opposition at the other end proved to be the home side's downfall in the end.
Campbellians look a useful outfit and will no doubt prove to be even tougher opponents on the synthetic surface. Down face the Belfast side on the opening day of the Senior Two campaign and end their quest for the title with a home game against the new new boys next March. ItÕ' certainly going to be an interesting season.
But back to the cup clash. Down were missing Jeremy McCready, Sinclair White, Paul Neill and Chris Taylor from their line-up, but were determined to start the season with a bang. While their performance wasn't exactly a damp squib, Down's players know they are capable of an awful lot more and must produce a top drawer performance against Parkview this Saturday.
Ashley Gibson and Mark Elliott, the scourge of countless Senior Two defences last season, again combined well, but failed to make a major impression and were often starved off possession.
Gavin Ringland went close in the first half with one shot, while Aaron Minnis was again impressive at the heart of the home defence. One of the best defenders in senior hockey, Down's aim of securing promotion this season will be built on the solid foundation the likes of Minnis and Duff provide at the back.
After a goalless first half, Down were determined to make a big impression in the second half, with Paul Tate going close. Elliott also went close when he powered his way into the circle but instead of shooting, he unselfishly opted to try and pick out strike partner Gibson and the chance was lost.
Campbellians opened the scoring midway through the half with what was a rather scrappy goal. Their second also came courtesy of the Down defence's inability to clear the ball, despite having several opportunities to do so.
With Parkview and Queen's still to play in the Linden Cup, Down aim to use both games as vital preparation for the new league campaign.
Taylor and McCready will be available for the opening league game away to Campbellians from which the locals must take something. Any assault on the title needs consistency at home and picking up points away from Malone Park.
Not many teams look like taking points off the new Belfast side this season so a point from the opening league encounter would not be a disaster by any means.

redpajama_set_name: RedPajamaCommonCrawl


DENVER – A popular Colorado trail where a rock slide killed five members of the same family will remain closed at least until spring, the U.S. Forest Service said Wednesday.
Forest Service experts will have to inspect the site to see if it is feasible and safe to rebuild the trail after it was buried by boulders on Monday, said John Peterson, deputy supervisor for the San Isabel National Forest, which manages the trail.
The inspection won't happen until after the coming winter, Peterson said.
The slide killed a couple from the nearby town of Buena Vista, one of their daughters and two of their nephews from Missouri. Another daughter survived with a broken leg after her father shielded her.
The Chaffee County Sheriff's Department identified the dead as Dwayne Johnson, 46, Dawna Johnson, 45, and their 18-year-old daughter, Kiowa-Rain Johnson.
The other victims were identified as Baigen Walker, 10, and Paris Walkup, 22, both of Birch Tree, Mo. They were nephews of Dwayne and Dawna Johnson.
Gracie Johnson, 13, told rescuers her father jumped on top of her when boulders began to crash down around them. Deputy Nick Tolsma, one of the first rescuers on the scene, said Dwayne Johnson probably saved his daughter's life.
Gracie was being treated at The Children's Hospital in suburban Denver. The hospital said the girl and her family were grateful for the public's concern but had no other comment. The hospital said it could not release any information about her condition.
A memorial service for the Johnsons was set for Saturday in Buena Vista. Separate services were being organized for the nephews in Missouri.
The short, scenic trail to Agnes Vaille Falls is a local favorite, but Undersheriff John Spezze has said it should be closed permanently because of the rock slide danger. Spezze didn't immediately return a phone message Wednesday.
Peterson said the Forest Service will consult with the sheriff's office and area residents before deciding whether to reopen the trail.
"We'll look at the site and see if it's a smart thing," Peterson said. "Physically, whether we can (reopen it), and geologically, whether we should."
What triggered the slide is still under investigation.
Life-threatening rock slides are rare and difficult to prepare for and protect against, Peterson said.
"It's such an extreme event, and it's so uncommon, I don't know what you do," he said.


New photos launcher promising anti-aircraft missile system of medium-range "Knight" for the first time demonstrated the general public on June 19 at the site of "GOZ Obukhov plant" (St. Petersburg, the company is a member of OJSC "Concern PVO" Almaz-Antey ").
Rights in this material belong to the i-korotchenko.livejournal.com.
The material was placed in the public domain owner.


text:
Comprehensive in its approach, and innovative in its methods, our Center was founded in 1966 to address the growing needs for childcare in Westchester County.
The Center has since evolved into a multifaceted program offering a myriad of early childhood educational programs and services to families and children that reside or work inthe County.
The Lois Bronz Children's Center offersa ground-breaking infant nursery; a toddler and two year old program; a pre-school andFederal Head Start program; Universal Pre-K; a before and after-school program for elementary school children; and Stepping Stones, a New York State certified special education pre-school Program. Our children also participate in many extra-curricular and enrichment activities, programs and services. OurCenter is a well-equipped facility which enables us tocare for approximately 200 children annually.
The Lois Bronz Children's Center (LBCC) is committed to creating a safe and nurturing educational center in which families, teachers and staff are in partnership. We provide an environment that enables each child to grow physically, intellectually, emotionally, culturally and socially. We value each and every child and strive to ensure that they reach their maximum potential.
The need for organized childcare in Greenburgh, NY was clearly demonstrated when the 1960 census indicated that 55 percent of the women living in the Fairview community were employed, and were forced to make whatever arrangements they could for their young children.
The Lois Bronz Children's Center has always been a community effort, and the childcare staff and administrative staff are the backbone of our success. Great leadership has been a key factor in our longevity and growth, and the Center has consistently secured and maintained a strong Board of Directors and Executive Directors.
Click here to view LBCC Career Opportunities
Sonja Washington Fitzgerald was appointed President/CEO on February 1, 2014. In partnership with Sonja, LBCC is making great strides to accomplish the goals set forth in the Strategic Plan, and has strengthened its allegiance to the community by holding steadfast to our mission of developing the genius in every child.
Our teachers are experienced, caring and committed to the growth and development of each child. LBCC teachers are required to participate in extensive and ongoing staff development program that enables them to integrate current teaching techniques and curriculum into their classrooms.
Staff consist a President/CEO, a Director of Education, a Family Service Director, a Stepping Stones Director, a Human Resources/Facility Director, a Registered Nurse, and a host of teachers and assistance teachers. We also have a host of ancillary and support staff members.
View our Board of Directors
4735 Washburn Street
Baton Rouge, LA 70814 | 225-333-7714
Provided by Applegate Consulting, Nonprofit Consulting, Coaching, and Training
Home Contact Us FAQs Events Calendar
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text:
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<LINK REL ="stylesheet" TYPE="text/css" HREF="../../../stylesheet.css" TITLE="Style">

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org.zeprs.data

Interface CreatedOrderable

public interface CreatedOrderable

Interfaced used for display order sorting. See also
 DisplayOrderComparator

Method Summary

 java.sql.Timestamp
getCreatedOrder()

 void
setCreatedOrder(java.sql.Timestamp created)

Method Detail

getCreatedOrder

java.sql.Timestamp getCreatedOrder()

setCreatedOrder

void setCreatedOrder(java.sql.Timestamp created)

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redpajama_set_name: RedPajamaGithub


Quench your Thirst... with One!
With water from the "Vitsi" spring!
The original recipe of Florina's orangeade and the unique quality of the region's water, are the secrets that make the orangeade ONE your favorite soft drink!
Lemonade ONE! Ultimate taste and flavor that you feel it in every sip!
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The objective of this research is to explore the level and nature of project risk management within the South African construction industry. It also investigates the possibility of relationships existing between the level of risk management and various company profiles, and also to identify the most critical risk types. The questionnaire, which was finalised after conducting a pilot study, was mailed out to a total of 176 recipients, all of whom were either members of or associated to, various, professional construction and engineering associations. Of the 176 questionnaires sent out, only 17.6% responded. Even still, the information collected proved successful in revealing the level and nature of project risk management within the industry, and provided valuable information specific to the various types of company specialisation. The results indicated a high probability of relationships existing between the level of risk management and various company profiles, but the exact nature of this relationship was not determined. The most critical risk types within the industry were identified as time constraints, late payments, nature of client, and skills & knowledge. Project managers from industry corroborated the findings of this research, with the exception of the critical nature of the risk type skills & knowledge. They found it difficult to justify its high ranking, and proposed a possible misunderstanding on the part of the respondents between skills & knowledge and the risk type protection of knowledge & intellectual property. Recommended future research include the identification and/or development of a risk management model tailored for the various segments of the South African construction industry, and an investigation into the exact nature of the possible non-linear relationships between the level of risk management and various company profiles. Also, re-investigation of the possibility of a relationship between the number of contracts annually and the level of risk management, and reasons why the risk types contract pricing and quality does not feature in the top five list of critical risks, is recommended.


text:
The Patterns Of Africa
Tuesday, July 16 2019 @ 01:37 pm ACST
Contributed by: Wesley Hull
It is wrong to say that the influx of players from African countries is an "experiment" in the same way that the influx of Irish is sometimes referred to as the "Irish Experiment". It certainly isn't. The increase in players of African descent is a result of Australian Rules football embracing the changing nature of our population and more players with diverse ethnic and cultural backgrounds will continue to grow.
That said, it is very interesting to see what is occurring with players in the AFL/VFL environment who come from Sudan, Kenya, Uganda, Ghana and other African nations. For the purpose of this story, players who were born in Australia but parents were born in their African country of origin are included – but not an exhaustive list.
There is s small but growing thread of evidence to say that players from African nations could become the archetypal ruckman of the future. Here is some proof.
Currently, Mabior Chol (Richmond) and Aliir Aliir (Sydney Swans) are revolutionising their team's ruck divisions. Born out of necessity rather than long-range planning, Chol and Aliir have become the fast, strong, high leaping ruckmen who have huge tanks and can inflict damage around the ground as well as at stoppages. Before being reborn as a defender prior to his injury, Majak Daw filled a similar role at North Melbourne.
A look at their physique already suggests power, athleticism and big engines (and guns). But that is now translating to the playing field as clubs realise that ruckmen don't need to be 200cm tall – they can be mid 190's and their athletic vertical leap can easily do the rest.
On average, the taller players from African nations are staying on lists longer, and it is that versatility to be ruck, key position player (KPP) or even oversized midfielder that makes them valuable.
Aliir Aliir (Sydney Swans/Kenya/Sudan – 196cm) has been a revelation this season since filling the hole left by injured Swan ruckmen in Sinclair and Naismith. His ruckwork obliterated Essendon ruckman Zack Clarke recently and has reset Swans' thinking.
Mabior Chol (Richmond – 200cm) Is a giant and also got his chance through Tiger injuries to Nankervis. In recent weeks, he has become better and better with more game time and not coincidentally, Richmond has been improving.
Majak Daw (North Melbourne – 195cm) Whilst the focus has rightly been on his extraordinary comeback from serious injury, Daw has also worked hard to find his niche in footy. His early days marked him as a key forward and backup ruckman. Prior to his injury, his breakout season in 2018 saw him patrolling the defence as a tall intercepting half back. However, he has rucked to good effect in the past and can still offer that – especially in a post-Goldstein world.
Essendon's Tom Jok (193cm) has been able to pinch hit in the ruck though his strength is more in the area of KPP or tall midfield type. It is too early to call his value, but he already has a reputation for baving great endurance and speed – especially for a big man. Gach Nyuon played for the club as well as a 198cm ruckman before being delisted. He is now at Doveton in suburban Melbourne.
This information augurs well for Sydney Swan Joel Amartey (Ghana – 197cm). Whilst born in Australia, he also possesses the hallmark athleticism and strength mentioned in other African nation players. When Swans NEAFL ruckman, Darcy Cameron, was injured, Amartey stepped up and hasn't looked back. He hopes to get a Swans' call-up this year and bring his talents to the biggest stage.
It could be argued that big-bodied types from African countries are the new prototype for AFL ruckman – big, strong, tall, fast, leap tall buildings and so on. Time will tell, but they bigger players are having better luck than smaller bodies. Emmanuel Irra (Port Adelaide – Uganda) was delisted by his club last year and former Brisbane Lion, Reuben Williams, was delisted and most recently came to fame playing for the Footscray VFL team receivingon-field tutoring from Hawk legend Jarryd Roughead. Both struggled to get high enough on the mid-sized hierarchy at their respective teams.
West Coast are still hopeful they will see their own Tarir Bayok (Sudan, 175cm) excel, but to gain a running midfield role or crumbing forward he has plenty of players ahead of his. Again, Tarir may be the exception and have a great career, but that isn't reflected yet in his games this year with East Perth reserves averaging 12 disposals a game as a mid/forward.
It is way too early to make a definitive statement about the value of players from African nations to the fabric of the game. However, there is some evidence that the tall, powerful, athletic body types may one day change how ruckman play. As this pattern becomes clearer, you can bet that clubs will be seriously looking at all players for those roles, but ever so slightly more so the pool of talent coming from African countries.
Below - Joel Amartey (Sydney Swans)
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Wesley Hull


text:
Douze est un journal ivoirien. Le Douze est le seul quotidien sportif ivoirien au format tabloïd, il tire à  exemplaires.

Voir aussi
 Médias en Côte d'Ivoire

Presse écrite en Côte d'Ivoire
Presse quotidienne en Côte d'Ivoire
Presse écrite au format tabloïd
Média de football


Rebeca makes the music her heart tells her to make. She stands for hope, happiness, and harmony. She believes in standing up for what is right. and that what is right is not in question, indivisible, under God. Rebecas native language is Spanish, and she has thankfully assisted me in the work of translating the lyrics into English, to be useful to peoples whose first language is English.
We are dilletantes, in the antique sense of the word, which refers to people doing things because the like it. from the root word "delight".
there is only this moment.
let them go and keep on.
this was nothing more than the law of attraction.
Even when no one will care.
to talk to the Sky, where are you?


Congrats to the lucky winner. When will the new contest begin? Can't wait!!
I didn't get an email, so it's not me.
Congrats to the winner, but if they don't respond, I hope I might be lucky enough to get selected the 2nd time around.
I haven't had any emails hopefully they didn't bounce and I never got the winning email.
Maybe if you post winning name they will respond through site.
My son turns 12 today maybe if I cross my fingers I will win this for him..
Camper223 – I wish I could post the winners name but for privacy reasons I can't post without consent.


Red Barn Door is a large-scale painting on two abutting aluminium panels. From a distance, because of the glossy paint used by Hume, the painting has the appearance of a reflective red monochrome surface. On moving closer, an image of a pair of wooden barn doors becomes apparent. The 'z' shape wooden framework of the doors is raised (a result of Hume's 'drawing' their outlines using a form of silicon paste), whereas the planks of wood are delineated by a thin line of gold-coloured paint or ink. In such slight modulations of the chosen image, this painting returns to the series of 'Door Paintings' made by Hume between 1988 and 1991, such as Incubus 1991 (Tate T07184). These paintings of institutional doors, initially based on hospital doors, were both impersonal and democratic in their approach and subject. Red Barn Door, however, is also rather different; here the anonymous, functional and modern aspect of his earlier paintings is replaced by a pair of doors that are homely, reflective of a rural location and to some extent even exotic. Red Barn Door was painted in Hume's house and studio in upstate New York, a place he tends to visit annually each summer, and continues the strand of 'transatlantic romance' that the art historian David Anfam identified in Hume's series of paintings and sculptures exhibited in 2007 under the title American Tan (David Anfam, 'American Beauty', in American Tan, exhibition catalogue, White Cube, London 2007, p.7). Hume's solo show at Matthew Marks Gallery in New York in 2009, in which this painting was shown, also included another barn door subject, Blue 'n' Cream Barn Door 2009.
The critic and curator Francesco Bonami has explained that for Hume 'images are no longer representations, but real chunks of life, no less real than himself' (Francesco Bonami, 'Gary Hume "Reflection in a Golden Eye"', in Gary Hume, exhibition catalogue, Bonnefantenmuseum, Maastricht 1996, unpaginated). If Red Barn Door explores the difference between the painted and the real it does so paradoxically through the forceful expression of its own material and visual reality as both a thing and an experience. One aspect of this is Hume's use of gloss paint, something that has remained a current throughout much of his work. He has stated in this regard that 'the high-gloss finish … starts to have a life of its own because it reflects the environment the paintings are shown in … they make you think about light and about where the paintings begin and end' (quoted in 'Brilliant': New Art from London, exhibition catalogue, Walker Art Centre, Minneapolis 1995, p.45).
I'm actually starting to use everything rather than limit myself to one part of the vocabulary. And that came about through painting some doors again. I wanted to own them again and to see what would happen if I painted another one … It gave me permission to use any mark that I've ever used. There doesn't have to be a closure of my ideas or my methods. The whole bloody thing's open and I can wander around and take what I like.
Unlike other recent 'Door' paintings, however, Red Barn Door explicitly moves away from the model of the institutional double swing doors with round or square windows and reflects not just a renewed freedom in Hume's painting but also, in its American subject matter, confirms that 'transatlantic romance' identified by Anfam as one key subject of his recent work.
Gary Hume: Door Paintings, exhibition catalogue, Modern Art Oxford 2008.
Gary Hume, Yardwork, exhibition catalogue, Matthew Marks Gallery, New York 2009, illustrated, unpaginated.
Ulrich Loock and Iwona Blazwick, Gary Hume: A Cat on a Lap, London 2009.


On a private terrace above Barcelona's Sant Antoni barrio, fellow British exile Angela Carroll recreates the afternoon tea she so craved after being here 9 years without it. As I am often asked about the afternoon tea I used to host, which sadly is impossible for me to do at the moment, I like to pass on her details so tea and cake lovers of the city don't need to miss out.
Rooftop Tea's open events happen every two months and can be enjoyed by solo tea lovers or one or two friends, the group will never be more than 9. Don't be afraid to go alone, you're sure to meet someone you'll get along famously with.
For those who want a more intimate affair with just their own friends, for a birthday party, hen party, baby shower or reason of their choice, Angela will prepare a bespoke afternoon tea, personalised cake and give the terrace to her guests for 2 hours so they can make the most of their time together.
Depending on the season you'll be greeted with a glass of Pimms, a selection of savouries and finger sandwiches, of course followed by scones with clotted cream and jam and then three sweets, which can vary from desserts such as cupcakes, brownies, mini Eton mess or Victoria sponge. Let's not forget the tea and some bubbly cava to go with it all too.
To enjoy all of this and for dates of upcoming events, Angela can be contacted via the following social media, price for afternoon tea is 35 euros per head. Rooftop Tea can also be called upon for small private or business catering.


text:
package ru.osetsky.httpprotocol;

import org.slf4j.Logger;
import org.slf4j.LoggerFactory;

import javax.servlet.ServletException;
import javax.servlet.http.HttpServlet;
import javax.servlet.http.HttpServletRequest;
import javax.servlet.http.HttpServletResponse;
import java.io.IOException;

/**
 * Created by koldy on 29.06.2018.
 */
public class ListRole extends HttpServlet {
    private static final Logger LOG = LoggerFactory.getLogger(EditServlet.class);
    private final ValidateService logic = ValidateService.getInstance();
    @Override
    protected void doGet(HttpServletRequest req, HttpServletResponse resp) throws ServletException, IOException {
        req.setAttribute("roles",  logic.findAllRoles());
        req.getRequestDispatcher("/WEB-INF/views/ListRole.jsp").forward(req, resp);
    }

    @Override
    protected void doPost(HttpServletRequest req, HttpServletResponse resp) throws ServletException, IOException {
        //удаление пользователя
        resp.setContentType("text/html");
        this.logic.deleteRole(req.getQueryString());
        resp.sendRedirect(String.format("%s/listrole", req.getContextPath()));
    }
}


We sell this Stan's No Tubes Extra Valve Core because valve cores are inevitably easy to lose. The O-ring that seals the valve core inside the stem can also be damaged, causing leaks in the system. So whether you've lost yours or simply need a replacement to restore the performance of your tubeless tire system, this valve core will get the job done.
Valve cores are so easy to swap out, and also very easy to break. For their size and cost, you would be foolish to not have at least one on every ride. You never know what could happen out there, so be prepared for the simple repairs!
Nice to have if you valve cores get clogged or bent.
As mentioned by previous reviewers this is a must-have, especially if you run tubeless. Sealant is bound to gum up your valve and, when it does, free-flowing air is just a valve core swap away.
Tubeless valves are expensive and I bought way to many pairs before I realized you could just replace the core. Not sure why I never thought of that! Anyway, I had a pump that used to bend the tips and I could never set my tire pressure accurately because I'd lose air closing the valve. That pump is now in the trash and I've got a handful of these cores on hand for when they get gummy or don't want to seal like new.
I had a clogged valve core to the point where I couldn't put air in the tire, and air slowly leaked out when trying to release air. I put this core in and threw the old one away. It worked great! I'll have to buy some more to have some spares.
better than your standard valve core.
If you run tubeless, you will run into a scenario where your valve core gets clogged with sealant. If you have one of these handy, it is a quick fix to replace and get back to enjoying the ride for any issue you encounter with your valve core.
Just what I needed at an amazing price!
Went to go pump up my tires before a ride and this guy flew out into the grass and was lost forever. Now I always make sure to have a spare.
You need to have a few of these guys laying around if you are using tubeless. Eventually you are going to get a clogged valve and it takes just a few minutes to swap out the core.
great to keep in your repair kit at home. If you bend a valve or if it gets clogged it's easy to replace.
Don't bother with clogged valves. Just pay for a new insert and you will be much happier. It is worth it. If you're running tubeless, you will eventually have a clogged valve.
If you ride a tubeless setup, you should certainly consider having at least an extra one of these that lives in your tool kit at all times! I have destroyed these with a pump or an unlucky rogue rock bounce and if it wasn't for being able to buy and have a spare core in my kit, I would have had one heck of a miserable walk out of the woods. Protect your investment and experience, buy one for yourself and your riding buddies!
it's nice to have one of these on the trail, Ive needed to loan mine out to others who have bunged up theirs pumping up their tire and being a little too rough.
You can also steel them from old tubes as well as they are universal and save some dollars. I feel for $3 it may be over priced by $2 but I would pay $20 if I needed one and didn't have one on the trail.
You're valve core will fail and need to be replaced at the worst, most inconvenient time. I carry an extra in a little pouch with extra chain leak and tire boot. You can prepare to handle repairs, or prepare to walk.
My pump destoyed one of these. Probably user error. Now I keep a few extra in my toolbox.
Any chance this would work on a Mavic setup?


Become a furry masked marauder in this family-friendly first-person arcade game for virtual reality. As a raccoon, your job is to collect bits of food in the air along your way, and you'll find hidden bonuses under the sweets. Follow the ball of yarn, and hurry - you only have 3 minutes!


Taken from Mistajam's Radio 1/1Xtra show last night, here is a insane remix of Jammer's "Big Man", courtesy of dubstep dons Lost and Hatcha on the buttons. The original had a heavy focus on the MC talent on show (with features from Viper, JME, B Live, Scratchy, Lay Z, Sox & Flowdan), but these two have taken the instrumental completely next level. The sub-bass and drum smacks on show here are huge – love what these guys have done with it.
Don't know if this will ever get a release, but you can grab the original (along with remixes from Sticky, Zed Bias and DJ Q) from iTunes HERE.


Every two years, when it comes time to mount a political campaign in New Hampshire, it's not unusual for candidates for state office to tout the need to attract new businesses to the state – and rightly so.
Such policies are critical to the fiscal health of any state, but they are particularly important in New Hampshire, which relies heavily on business taxes to fund state government in the absence of a broad-based sales or income tax.
What tends to happen, then, is the rhetoric gets so hot, you can't blame voters for wondering whether they live in the least business-friendly state in the nation.
So before anyone jumps to any conclusions this time around, consider this: a new survey has found that New Hampshire, quite to the contrary, is among the most business-friendly states in the country.
business owners ranked New Hampshire No. 8, making it the only New England state to crack the top 10.
The survey was conducted by the professional services firm Thumbtack.com and the Ewing Marion Kauffman Foundation, which bills itself as the world's largest foundation devoted to entrepreneurship.
Survey respondents were asked to assess how easy it is to open a business in their state, what kind of support they received and whether they would recommend starting a business there to other entrepreneurs.
Survey respondents were asked to assess their state in 15 categories, such as the ease in starting a new business and the friendliness of regulations covering health and safety; employment, labor and hiring; licensing; environmental; and zoning.
Specifically, New Hampshire got "A" or "B" grades in the subcategories of overall friendliness, ease of starting a business, regulations, employment, tax code, licensing, environment and networking programs. The lowest grade – a "D" – was for the cost of hiring a new employee.
While acknowledging the state's low ranking in corporate taxes (No. 46) and property taxes (No. 41), the Washington-based foundation still ranked New Hampshire among the best states in the nation at No. 6, behind Wyoming, South Dakota, Nevada, Alaska and Florida – other states with no income tax, sales tax or both.
"The lesson is simple: a state that raises sufficient revenue without one of the major taxes will, all things being equal, have an advantage over those states that levy every tax in the state tax collector's arsenal," economist Mark Robyn wrote in this year's report.
So, by all means, let's have a spirited debate this election season over whether our government leaders are doing enough to attract and keep businesses – that is certainly a legitimate campaign issue.
But let's guard against those candidates who would distort the state's business-friendly reputation for sheer political expediency.


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JetBlue Park At Fenway South Tickets, JetBlue Park At Fenway South Seating Chart, Maps, Fort Myers, FL, Florida. Tickets and Information
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Nearby Fort Myers, FL
Alico Arena
Ballyorney Irish Pub
Barbara B Mann Performing Arts Hall
Broadway Palm Dinner Theatre
Centennial Park - FL
City Of Palms Park
Crowne Plaza Fort Myers At Bell Tower Shops
First Assembly of God - FL
Hammond Stadium at CenturyLink Sports Complex
Harborside Event Center
LA Best Bar & Grill
Lakes Regional Park
Millennial Brewing Company
Pizzando Lobo Event Center
Point Ybel Brewing Company
Sanibel Harbour Marriott Resort & Spa
Six Bends Harley Davidson
Suncoast Credit Union Arena
The Ranch Concert Hall & Saloon
Top Rocker Field
JetBlue Park At Fenway South Information and Schedule
JetBlue Park At Fenway South Seating Chart and Event Tickets
JetBlue Park At Fenway South seating charts and stadium tickets are available now at Ticket America. Please select one of the upcoming concerts or events from the dates below to view available tickets at the JetBlue Park At Fenway South We carry arena seating, box office seats and stadium club seating. We have seating charts, phone numbers, layouts, and map locations for all venues.
To purchase tickets directly for JetBlue Park At Fenway South events over the phone......please call 1-800-842-9750.
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JetBlue Park At Fenway South Address & Information
JetBlue Park At Fenway South Venue Name
11500 Fenway South Drive Address
Fort Myers Venue City
FL Venue State Abbreviation
Florida Venue State
33913 ZIP Code
United States of America Country
0 Number of Seats
1 Number of different stage layouts


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In Hong Kong and Macau, with Longman, Prentice Hall, and many other brands, Pearson is the leader in all education sectors, ranging from pre-school, primary, secondary and higher education through to adult learning.


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Moritz Wilhelm Drobisch
M. W. Drobisch.
Moritz Wilhelm Drobisch (16 August 1802 – 30 September 1896) was a German mathematician, logician, psychologist and philosopher. His brother was the composer Karl Ludwig Drobisch (1803–1854).
Drobisch studied mathematics and philosophy at the University of Leipzig, where he subsequently became a professor. He wrote his habilitation in 1824. From 1826 to 1868 he served as ordinarius (full professor) in mathematics, and from 1842 on as ordinarius in philosophy. He was rector of the university of Leipzig in 1840–41 and served as dean of the philosophical faculty several times. Drobisch made contributions to philosophical and mathematical logic, set theory, quantitative linguistics and empirical psychology. Drobisch was strongly influenced by Johann Friedrich Herbart.
In 1834, Drobisch joined the Count Jablonowski Society of the Sciences in Leipzig. In 1846 he was a co-founder of the Saxony's Royal Society of the Sciences, whose successor organisation has named a medal in his honour. In 1868, Drobisch resigned from the mathematics department to devote himself to philosophy. He was made an honorary citizen of Leipzig in 1876. In his later years, Drobisch suffered from advancing blindness, making scholarly work impossible from the mid-1880s on. Wilhelm Wundt, a pioneer of German empirical psychology, held Drobisch's funeral oration and acknowledged his influence. Drobisch was one of the forerunners of the neo-Kantian revival of the 1860s. Friedrich Albert Lange criticized him and Herbart in his Foundations of Mathematical Psychology (1865).
1834: Beiträge zur Orientierung über Herbart's System der Philosophie. [Contributions to the Orientation in Herbart's System of Philosophy.] Significantly revised and expanded editions in 1851 and 1863.
1836: Neue Darstellung der Logik nach ihren einfachsten Verhältnissen. Nebst einem logisch-mathematischen Anhange. [New presentation of Logic in its Most Basic Relations. With a Logico–Mathematical Appendix.]
1840: Quaestionum mathematico-psychologicarum. [Mathematical–Psychological Question.]
1842: Empirische Psychologie nach wissenschaftlicher Methode. [Empirical Psychology According to the Scientific Method.]
1846: Über die mathematische Bestimmung der musikalischen Intervalle. [On the Mathematical Determination of Musical Intervals.]
1850: Erste Grundlegung der mathematischen Psychologie. [First Foundation of Mathematical Psychology.]
1867: Die moralische Statistik und die menschliche Willensfreiheit. [Moral Statistics and Human Free Will.]
1876: Über die Fortbildung der Philosophie durch Herbart. [On Herbart's Continuation of Philosophy.]
1885: Kant's Dinge an sich und sein Erfahrungsbegriff. [Kant's Things in Themselves and his Concept of Experience.]
Heinze, M., 'Drobisch, Moritz.' In: Allgemeine Deutsche Biographie, Vol. 48. Leipzig 1904, pp. 80–82.
Best, K.H., 'Moritz Wilhelm Drobisch (1802–1896).' In: Glottometrics 17, 2008, pp. 109–114.
Neubert-Drobisch, W., Moritz Wilhelm Drobisch: ein Gelehrtenleben. Leipzig 1902.
Moritz Wilhelm Drobisch anlässlich seines 200. Geburtstages. Verlag der Sächsischen Akademie der Wissenschaften. Stuttgart and Leipzig, 2003.
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Retrieved from "https://en.wikipedia.org/w/index.php?title=Moritz_Wilhelm_Drobisch&oldid=896324485"
19th-century German mathematicians
19th-century German philosophers
19th-century German writers
19th-century German male writers
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German psychologists
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Home > News > World Heritage > Global > Marine
Photo: IUCN-PACO
IUCN receives special recognition award from the Government of Ghana
On 4th October, 2019, IUCN was honoured with a special recognition award from the Government of Ghana for the organisation's immense contribution to the REDD+ process in Ghana.
Photo: ©Ramsar Convention
World Wetlands Day: Strengthening resilience and collaboration to reduce disaster risk
On February 2nd the world celebrates its wetlands – complex ecosystems that provide a wide variety of services and benefits for people and nature. Wetlands such as estuaries, mangroves, marshes, and swamps play, beyond their biological...
Launching the report "World Heritage in the High Seas" at the edge of the Sargasso Sea Photo: © Nekton Mission
Sargasso Sea among spots in the High Seas identified as potential World Heritage sites
Five sites in the High Seas, which belong to no country, could be recognised under the World Heritage Convention, according to a new report by UNESCO's World Heritage Centre and International Union for Conservation of Nature (IUCN), the advisory body on...
Photo: IUCN / Elena Osipova
La UICN advierte del riesgo del comercio de vida silvestre y la construcción de presas para el Patrimonio Mundial natural
Los sitios naturales del Patrimonio Mundial se enfrentan a importantes amenazas, como la explotación forestal con fines comerciales, la caza furtiva, la pesca con redes de enmalle y la construcción de presas, según la Unión Internacional para la Conservación...
Le commerce d'espèces sauvages et les barrages compromettent le Patrimoine mondial naturel – UICN
Les sites naturels du patrimoine mondial font face à des menaces majeures, telles que l'exploitation forestière commerciale, le braconnage, la pêche au filet maillant et les barrages, selon l'Union internationale pour la conservation de la nature (UICN). Dans...
Wildlife trade and dams putting natural World Heritage at risk – IUCN
Natural World Heritage sites face major threats, such as commercial logging, poaching, gillnet fishing and dams, according to the International Union for Conservation of Nature (IUCN). In its recommendations to the World Heritage Committee, which meets in...


Garrett - Foster City : I'm passionate about fitness and sport and helping everyone reach their fitness goals. I train clients and teams to lose weight, get fit, eat right, be athletic and look great!
I have over 10 years coaching experience in multiple sports and as a strength and conditioning specialist. I have coached and trained athletes and individuals of all age groups - from youth to adults, preparing them to achieve weight loss goals, team sport competitions and individual athletic events. I've held strength and conditioning positions with the Temecula Halos youth baseball, San Diego Mesa College football, San Diego Enforcers semi-pro football and San Diego Power Surge Softball. I'm a proud member of the NSCA and NASM, holding certificates in personal training and speed/agility/quickness training.


I have been traveling for a few weeks now, on a journey filled with inner dialog. Searching first for long-desired destinations, I was soon digging deep into my childhood. It was a walk toward the past–a backtrack of the images and sensations that were important in forming my personality. Doing it together, in part, with my siblings, I was able to recreate some of the events I'd forgotten, and also shed a different light on the events that had anchored themselves in my mind for decades. My trip, therefore, was sort of like the Akira Kurosawa film Rashomon, in which all the protagonists have different recollections of the same event; different narratives that only manage to offset the perspectival subjectivity of events by adding them up, reconstructing them, and, in Kurosawa's case, explaining a murder. No murders in my case.
My travel took me to different places. I first crossed the Atlantic on the magnificent Queen Mary 2. Some of Yonder's readers had the impression that I did not have a good time on that boat. I loved it, it was a great experience, but it was a different kind of travel than what I expected, or what I wanted it to be for many years. It did trash my old quixotic notions of crossing the Ocean, replacing it with a more realistic one, enjoyable nonetheless.
No surprises of this kind in London, where I walked through Soho on the way to the National Gallery displayed the richness of the rich in the windows of high-end shops, fancy bars, and restaurants that no longer belong to locals (already a loose term in this city). London is changing fast and will be the first capital to be overrun by rich populations that some decades ago were called foreigners. If the referendum on the EU would have been called a few years later than it was, Britain would never, ever have voted for Brexit.
I was also very glad to see my own country prospering. Very few Slovenians would previously admit what some of them now do: Slovenia has a very high quality of life. The surprising thing is that it accomplished it with much less wealth than London. The country has a much smaller GDP and revenue, people have much lower salaries, but they are surrounded by beautiful nature and good food that is getting increasingly better, even selective. If only they would smoke less! For someone who is used to the crowded streets and noise of New York, Slovenia seems to possess endless space and that deep-resting silence and peace. And yet my country is a small, hard-working, bustling place.
What makes me happy about the country is that it is investing money to unearth the historical sites like, for example, an entire Forum of a small city of the Roman Empire, or some medieval palaces and tombs that for many years were covered by some socialist trash. Even in a small city like Celje, where I was born, there are now cultural and historical sites that I never saw when I was growing up there; the city is full of them. We had our fun as kids, but instead of having it among the Roman ruins, we grew up among big socialist planters.
Ljubljana, the town I consider mine in Slovenia, has gone through a real urban revival. Sure, being the nation's capital, the city is spending more than any other in the country, upsetting other cities like Maribor. But the money in once-sleepy Ljubljana seems to be well spent and it's now blossoming, crowded with mostly young visitors. I would love to see the figures on the number of visitors, as the invasion of tourists is such that the shopkeepers and restaurant staff in the old part of the city have stopped using the local language. The visitors, on their end, are trying to learn some of the Slovene language.
In my time in Ljubljana, I knew every foreigner who came to town. It would be a guest professor, lecturer, some foreign friends of friends, my friends visiting. Ljubljana is now flooded with tourists coming from all parts of the world. The city received them, with so many new sites that so nicely add to the architecture known in Plecnik town.
There is a very systematic effort to offer a fresh look that respects the original aesthetics, traditions of the country. That includes some old ideas that were made for the city at the beginning of the last century but were never implemented. It is so nice to see those old plans coming out of the drawers, being altered, improved, then implemented. There are new bridges; there is now life on the small river Ljubljanica, which curves through the city. There are so many ways to walk the city and see new perspectives, added to the old ones; there are many small details and renovations that make the city a subtle testament to our culture and our modernity. There are lovely bars and restaurants on every corner. And the city is in the hands of the youth. Finally.
There are so many things that I saw and noted and there are plenty of reminiscences that have no place here. So this issue of Yonder is just a short traveling note that will probably generate a couple of interesting stories later on. In the meantime, I wanted to send you this postcard with some of the images of my old city and the new world.


HOUSEHOLDS in South East Clare remain without water as Irish Water carry out essential works to repair a burst water main which has affected the water supply in the Shannon Banks, Westbury and Ardnacrusha area.
The local authority is now advising motorists of traffic congestion due to the unplanned works being undertaken by Irish Water to resolve the issue.
Homes and businesses in the locality were affected by disruptions to their water supply and reduced water pressure on the Mill Road, Corbally Road, Irish Estates, Shannon Banks, Westbury and outwards to Barrys Cross and surrounding areas.
Works have an estimated completion time of 2pm. However this afternoon Limerick City and County Council said that water is not expected to return to the area until 7pm this Tuesday evening.
The local authority is also advising motorists to avoid the Corbally Road and to use the R464 through the Long Pavement and Parteen as severe traffic congestion is expected on this road this evening.
The areas affected include Mill Road, Corbally Road, Irish Estates, in Limerick, and Shannon Banks, Westbury and outwards to Barrys Cross, in Clare.


The german phone code 04478 represents Cappeln (Oldenburg) in Niedersachsen.
Note for calls from abroad: In addition to the German country code (+49 or 0049) you can omit the foregoing zero of the dialling code for Cappeln (Oldenburg). So you can dial +494478... and add the number of the phone line you want to reach.
Wich place is a "must see" for a tourist in Cappeln (Oldenburg)?


A truly satisfying crunchy and fruity granola chock-full of oats and freeze dried raspberries, sweetened with evaporated cane juice, honey and a touch of vanilla.
Oats, Honey, Evaporated Cane Sugar, Water, Canola Oil, Natural Flavor, Raspberries, Salt. Packaged In A Facility That Processes Peanuts, Tree Nuts, Milk, Egg, Wheat And Soy.