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Int J Med Sci 2007; 4(1):28-35. doi:10.7150/ijms.4.28 This issue
Functional genomics analysis of low concentration of ethanol in human hepatocellular carcinoma (HepG2) cells. Role of genes involved in transcriptional and translational processes
Francisco Castaneda1, Sigrid Rosin-Steiner1, Klaus Jung2 3
1. Laboratory for Molecular Pathobiochemistry and Clinical Research, Max Planck Institute of Molecular Physiology, Dortmund, Germany
2. Department of Statistics, University of Dortmund, D-44221 Dortmund, Germany
3. Medical Proteom-Center, Ruhr-University Bochum, D-44780 Bochum, Germany
Castaneda F, Rosin-Steiner S, Jung K. Functional genomics analysis of low concentration of ethanol in human hepatocellular carcinoma (HepG2) cells. Role of genes involved in transcriptional and translational processes. Int J Med Sci 2007; 4(1):28-35. doi:10.7150/ijms.4.28. Available from https://www.medsci.org/v04p0028.htm
We previously found that ethanol at millimolar level (1 mM) activates the expression of transcription factors with subsequent regulation of apoptotic genes in human hepatocellular carcinoma (HCC) HepG2 cells. However, the role of ethanol on the expression of genes implicated in transcriptional and translational processes remains unknown. Therefore, the aim of this study was to characterize the effect of low concentration of ethanol on gene expression profiling in HepG2 cells using cDNA microarrays with especial interest in genes with transcriptional and translational function. The gene expression pattern observed in the ethanol-treated HepG2 cells revealed a relatively similar pattern to that found in the untreated control cells. The pairwise comparison analysis demonstrated four significantly up-regulated (COBRA1, ITGB4, STAU2, and HMGN3) genes and one down-regulated (ANK3) gene. All these genes exert their function on transcriptional and translational processes and until now none of these genes have been associated with ethanol. This functional genomic analysis demonstrates the reported interaction between ethanol and ethanol-regulated genes. Moreover, it confirms the relationship between ethanol-regulated genes and various signaling pathways associated with ethanol-induced apoptosis. The data presented in this study represents an important contribution toward the understanding of the molecular mechanisms of ethanol at low concentration in HepG2 cells, a HCC-derived cell line.
Keywords: human hepatocellular carcinoma cells, HepG2, ethanol, gene expression, transcriptional and translational processes
Studies using the human hepatocellular carcinoma (HCC) cell line HepG2 have demonstrated a specific gene expression pattern induced by ethanol different from that observed in normal livers and in livers with alcoholic liver disease [1, 2]. In vivo studies using animal models, including rats [3], mice [4], and baboons [5] as well as human liver samples obtained from patients with advanced alcoholic liver disease [5], revealed changes in the expression of genes coding for transcription factors, signaling molecules, stress response and ethanol metabolism [1]. These studies, however, have been performed using high concentrations of ethanol.
Gene expression profiling using microarray technology allows the expression analysis of thousands of genes simultaneously [6-8]. This method is more informative than nonparallel studies on single genes [9, 10] providing information of networks of gene expression changes [11] [12]. The cDNA microarray technique has been used to evaluate the global gene expression in HCC as well as HCC-derived cell lines [13-16]. Moreover, HepG2 cells can be used to analyze the effect of ethanol on gene expression in HCC, based on the fact that HepG2 cells retain the genomic expression of HCC [15, 17, 18].
We previously reported the effect of ethanol at low concentration (namely 1 mM) on induction of different signaling pathways initiated through protein kinases phosphorylation with subsequent expression of transcription factors (AP1, Elk1, Stat1, SRF and NFκB) and expression of apoptotic genes (Fas receptor, Fas ligand, FADD and caspase 8) [19]. However, the effect of low concentration of ethanol on genes involved in transcriptional and translational processes remains to be characterized. Therefore, the aim of this study was to identify the effect of low concentration of ethanol (1 mM for 6 h) on gene expression, specifically from genes with transcriptional and translational function, in HepG2 cells compared to HepG2 cells not exposed to ethanol (control cells) using cDNA microarrays. We identified four significantly up-regulated (COBRA1, ITGB4, STAU2, and HMGN3) and one down-regulated (ANK3) gene. Notably, none of these genes have been previously associated with ethanol with the exception of ITGB4 that has been found up-regulated with high concentrations of ethanol.
This study represents an important advance in the characterization of the molecular mechanisms of low concentration of ethanol in HepG2 cells. Moreover, it constitutes a necessary step in the understanding of the molecular mechanisms involved in alcohol-induced effect in human hepatocellular carcinoma cells. In addition, this represents a novel approach for the identification of potential targets in the diagnosis and treatment of human hepatocellular carcinoma.
Based on the reported alteration of gene expression of primary human hepatocytes in monolayer cultures [20] and the conserved gene expression profile in confluent HepG2 cells in vitro [21], the present study was performed only using HepG2 cells.
HepG2 cells were seeded in 250 ml tissue culture flasks (Falcon, Heidelberg, Germany) at 1x105/ml concentration in 10 ml RPMI-1640 medium (Gibco, Eggersheim, Germany) supplemented with 10% fetal bovine serum (Boehringer Mannheim, Germany), 100 U/ml penicillin and 100 µg/ml streptomycin (ICN, Meckenheim, Germany) at 37°C in a humidified atmosphere of 7.5% CO2. The cells were grown to 80% confluence. After 2 days of cell culture, the cells were harvested with 0.05% trypsin / 0.02% EDTA (Gibco) and seeded in 6-well plates (Falcon) at concentrations of 1x105/ml. Six sets of experiments were performed. Each set consist of two groups as follow: group 1, HepG2 treated cells with 1 mM ethanol for 6 h; and group 2, HepG2 cells without ethanol exposure used as a control. All chemicals were purchased from Sigma Aldrich (Seelze, Germany).
Both the ethanol concentration at millimolar level (1 mM) and the exposition time (6 hr) were chosen based on the data obtained from previous studies [22-24]. They demonstrated that ethanol at low concentrations selectively induces apoptosis in HepG2 cells without causing cell toxicity, which represents the hallmark of the ethanol effect when high concentrations are applied [25].
Total RNA extraction and microarray hybridization
Total RNA was extracted using RNase kit (Qiagen, Hilden, Germany) and its quality was confirmed by electropherograms using a 2100 BioAnalyzer (Agilent, Santa Clara, CA). Total RNA (5 µg) were used for preparing biotinylated cRNA using GeneChip IVT Labeling Kit (Affymetrix, Santa Clara, CA). After confirmation of the quality of labeled cRNA using the Affymetrix Test 3 Array, cRNA was converted to cDNA using GeneChip One-Cycle cDNA Synthesis Kit (Affymetrix). Fifteen micrograms of labeled and fragmented cRNA were subsequently hybridized to a Human Genome U133 plus 2.0 microarray (Affymetrix). After the hybridization, the DNA microarrays were washed and stained on a Fluidics Station (Affymetrix) according to manufacturer's instructions. Finally, the DNA microarrays were scanned with a GeneChip Scanner 3000 (Affymetrix).
DNA microarray analysis
Data analyses were performed using the GeneChip Expression Analysis Software (version 3.2, Affymetrix). First, single array analysis was performed [11] to calculate for each gene a signal, which represents a relative measure of the abundance of the transcript with a detection p-value. To evaluate the gene expression profile between group 1 (ethanol-treated) and group 2 (control) a hierarchical cluster analysis was performed [26-28].
For a quantitative estimation of the change in gene expression between both groups a pairwise comparison analysis was performed. For that purpose a signal log ratio (SLR; basis 2) using a one-step Tukey's biweight method was calculated [29] [30]. Genes with a SRL > 1 or <-1 in at least 3 experiments (50%) were selected for further analyses.
Quantitative real-time PCR Analysis
Quantitative real-time PCR was used to validate the effect of ethanol on gene expression. Total RNA was isolated from HepG2 cells using RNAsy kit (Qiagen) and RNA quality was evaluated using RNA 6000 Nano Chip Kit and Bioanalyzer 2100 (Agilent, Böbligen, Germany). Real-time PCR was performed using the QuantiTect SYBR green RT-PCR kit (Qiagen). Specific primers for each selected gene were used. A quantitative real-time PCR determination using the Optical System Software (iQ5 version 1.0) provided with the BioRad iQ5 cycler (BioRad, Munich, Germany) was performed. The following primers were used: ITGB4 forward, 5'-CCTGTACCCGTATTGCGACT-3'; ITGB4 reverse 5'-AGGCCATAGCAGACCTCGTA-3'; COBRA1 forward 5'-TGAAGGAGACCCTGACCAAC-3'; COBRA1 reverse 5'-ATCGAATACCGACTGGTGGA-3'; ANK3 forward 5'-GGAGCATCAGTTTGACAGCA-3'; ANK3 reverse 5'-TTCCACCTTCAGGACCAATC-3'; STAU2 forward 5'-CCGTGAGGGATACAGCAGTT-3'; STAU2 reverse 5'-GCCCATTCAGTTCCACAGTT-3'; HMGN3 forward 5'-TGCCAGATTGTCAGCGAAAC-3; HMGN3 reverse 5'-TGCTCCACCAAAACCTGAACCAAAC-3. All primers were synthesized by MWG Biotech AG (Ebersberg, Germany). Samples were prepared in triplicate and real time PCR measurement for each sample was done in duplicate. The expression level of each gene was normalized using the control group (group 2) and an induction ratio (treated/control) was obtained. The average of duplicate real time PCR measurements was used to calculate the mean induction ratio ± SD for each gene.
Data are expressed as mean values ± standard deviation (SD). Results from HepG2 cells treated with 1mM concentration of ethanol (group 1) were compared to non-treated HepG2 cells (control cells, group 2) using Student's t-test. Statistical significance was assumed at p level <0.05 level. SigmaPlot software version 8.02 (Systat Software, Erkrath, Germany) was used for statistical analysis.
Statistical analyses of microarray data were performed using a permutation procedure [31, 32] as well as a non-parametric method [33]. These two methods allowed us to analyze whether a gene had no expression change (null hypothesis) or whether it did (alternative hypothesis). Based on the expression measurements, a decision is made either for the null or the alternative hypothesis. In order to keep the number of false positive decisions small, the two testing procedures were set up to control for the family-wise error rate (FWER), which is the probability of having more than one false positive decision among all n tests. In particular, the testing procedures guaranteed an FWER ≤ 0.05 [34].
Low concentration of ethanol selectively expresses genes involved in transcriptional and translational processes
Figure 1 shows the hierarchical gene expression profile of 1 mM ethanol concentration treated HepG2 cells (group 1) and control cells (HepG2 cells without treatment; group 2) exposed for a 6 h period. Data are presented as a median of the signal obtained from the six different microarrays for each group (n=6). Each single array had good quality control and showed a normal distribution and linearity. The red zones indicate up-regulated gene expression and the green zones indicate down-regulated gene expression. The gene expression pattern between the two groups revealed a relatively similar pattern, suggesting that only few genes are changed with exposure of a low concentration of ethanol. The pairwise comparison analysis demonstrated the selective effect of ethanol on fives genes involved in transcriptional and translational processes. As shown in Table 1, the up-regulated genes were COBRA1, ITGB4, STAU2, and HMGN3 with a SLR of 3.30, 2.61, 1.68 and 1.52, respectively. ANK3 was the only significantly down-regulated gene with a SLR of -5.02.
Hierarchical clustering analysis of gene expression profile in ethanol-treated HepG2 cells (1 mM ethanol for 6 h, Group 1) compared to control HepG2 cells (Group 2). Each row represents the mean of signal log ratios (n=6 arrays each group) using a color-code scale. Red represents expression greater than reference, green is less than reference, and gray is missing or excluded data.
Ethanol-regulated genes obtained from the pairwise comparison analysis between ethanol-treated (1 mM for 6 h) and control HepG2 cells.
Probeset
Gene title
Signal Log Ratio
202757_at COBRA1 cofactor of BRCA1 ▲ 3.30 regulation of transcription NM_015456
204990_s_at ITGB4 integrin, beta 4 ▲ 2.61 protein binding NM_000213
204226_at STAU2 staufen, RNA binding protein, homolog 2 (Drosophila) ▲ 1.68 double-stranded RNA binding NM_014393
209377_s_at HMGN3 high mobility group nucleosomal binding domain 3 ▲ 1.52 DNA binding NM_004242
206385_s_at ANK3 ankyrin 3, node of Ranvier (ankyrin G) ▼ 5.02 protein binding NM_001149
▲- increased
▼- decreased
Validation of microarray results by quantitative real time RT-PCR analyses
In order to validate the observed expression on the ethanol-regulated genes (COBRA1, ITGB4, STAU2, HMNG3, and ANK3), we performed quantitative real time RT-PCR in HepG2 cells treated with ethanol. The primers used showed a linear specificity. The results were normalized to control mRNA level (i.e. HepG2 cells without ethanol treatment). We did not use housekeeping genes, such as GADPH, actin or LDHA, because ethanol also alters the expression of these genes (data not shown). The relative mRNA level for each gene is shown in Figure 2. The obtained mRNA level for COBRA1, ITGB4, STAU2, and HMGN3 was 38.0, 22.7, 5.5, and 3.8, respectively. In the case of ANK3, the real time RT-PCR did not give any transcript with two different primers. This might be due to the strong down-regulation of ANK3 observed with ethanol treatment. The results from semi-quantitative RT-PCR quantified and confirmed the findings of the microarray analysis on gene expression in response to ethanol.
Validation of ethanol-regulated genes by real time RT-PCR. mRNA levels of ethanol-regulated genes determined by real time RT-PCR. Induction ratios of each gene (fold change) by ethanol were calculated using expression level, normalized to the level of the control group (HepG2 without ethanol treatment). Experiments were done in triplicate (n=3) and error bars indicate standard deviation among the triplicate samples.
Gene ontology analysis
Once the ethanol-regulated genes were validated, we analyzed further their implication in different biological processes. For this purpose, the ethanol-regulated genes were functionally clustered into specific biological processes from the classification systems of the gene ontology annotation [35]. The gene ontology analysis of the identified genes is shown in Table 2. The biological processes associated with the up-regulated genes in the ethanol-treated HepG2 cells were as follow: regulation of transcription for COBRA1; cell communication, cell adhesion, cell-matrix adhesion, integrin-mediated signaling, and development for ITGB4; transport for STAU2; and an unknown biological process for HMGN3. The biological processes in which ANK3, the down-regulated gene, was involved were protein targeting, cytoskeletal anchoring and signal transduction.
Additionally, we evaluated the functional pathways in which the ethanol-regulated genes were involved using KEGG (Kyoto Encyclopedia of Genes and Genomes) [36] and GenMAPP (Gene Microarray Pathway Profiler) [37] analysis. As shown in Table 2, only ITGB4 was found to be involved in intracellular pathways including cell communication, focal adhesion, extra cellular matrix-receptor interaction and regulation of cytoskeleton. These data suggest an important role of integrin in the molecular mechanisms of ethanol effects in HepG2 cells. The other ethanol-regulated genes were not found to be associated with any specific pathway.
Gene ontology in terms of biological processes of the ethanol-regulated genes in HepG2 cells.
Gene ontology (GO) biological process
KEGG/ GenMAPP Pathway
COBRA1 GO:0006350 transcription --
GO:0006355 regulation of transcription, DNA-dependent --
ITGB4 GO:0007154 cell communication hsa01430 Cell Communication
GO:0007155 cell adhesion hsa04510 Focal adhesion
GO:0007160 cell-matrix adhesion hsa04512 ECM-receptor interaction
GO:0007229 integrin-mediated signaling pathway hsa04810 Regulation of actin cytoskeleton
GO:0007275 development --
STAU2 GO:0006810 transport --
HMGN3 GO:0008150 biological process unknown --
ANK3 GO:0006605 protein targeting --
GO:0007016 cytoskeletal anchoring
GO:0007165 signal transduction
Functional genomics analysis of ethanol-regulated genes
In an effort to find gene regulatory networks associated with low concentration of ethanol, we analyzed the interaction between the ethanol-regulated genes studied using Pathway Architect software (Stratagene). Figure 3A shows the reported interactions of each of these genes. ITGB4 and ANK3 are associated with different targets, including small molecules, genes and proteins. In contrast, COBRA1, STAU2 and HMGN3 are only associated with very few targets. Figure 3B shows the reported interaction network between ethanol and the five ethanol-regulated genes of interest. Of note, ITGB4, COBRA1 and ANK3 are indirectly associated with ethanol through phosphatidylinositol, GTP and chloride, respectively. There are until now no reported interactions observed for STAU2 and HMGN3. Figure 3C shows the interaction of ethanol with similar signaling pathways, in which ethanol-regulated genes are also involved. Such pathways include ERK-PI3K, AKT, NO, cAMP-PKA, PTEN, G-Protein-MAPK, NGF, and PDGF signaling. This finding corroborates the interaction observed between various intracellular signaling pathways and apoptosis induced by 1mM concentration of ethanol in HepG2 cells [19].
Functional genomics of low concentrations of ethanol in HepG2 cells. (A) Reported interactions of each ethanol-regulated gene studied. (B) Indirect interaction of ITGB4, COBRA1 and ANK3 with ethanol, as reported in the literature. (C) Interaction of ethanol with similar signaling pathways in which COBRA1, ITGB4, STAU2, HMGN3, and ANK3 are also involved.
The gene expression profile of HepG2 cells exposed to a low concentration of ethanol (equivalent to 1mM) demonstrates a totally different pattern to that observed with exposure to ethanol at high concentrations. Ethanol at high concentration modulates multiple functional interactions explaining its toxic effect in the liver. In vitro studies using HepG2 cells over-expressing CYP2E1, an ethanol metabolizing enzyme, demonstrated that high concentrations of ethanol (100 mM) induced the expression of genes involved in the metabolism of ethanol [16]. In addition, the metabolism of ethanol results in an increased production of toxic metabolites such as free radicals. These metabolites have an effect on gene expression [30]. In contrast, our findings suggest that 1mM concentration of ethanol regulates genes that are not directly involved in ethanol metabolism. Specifically, the gene expression profile induced by this low concentration of ethanol suggests a balance between biological processes, as shown by the pattern of up- and down-regulated genes we observed. Among the ethanol-regulated genes we found, only ITGB4 has been reported in association with ethanol. Chronic ethanol consumption increases the expression of integrins but impairs hepatocyte attachment and spreading on various extracellular matrix substrates [38].
Importantly, low concentration of ethanol exerts its effect through induction of transcription factors (AP1, Elk1, Stat1, SRF and NFκB) and expression of apoptotic genes (Fas receptor, Fas ligand, FADD and caspase 8) [19]. In addition, as confirmed by the functional genomics analysis presented in this study, ethanol at low concentration (1 mM) also regulates the expression of genes involved in transcriptional and translational processes.
Integrins act as signal transducing molecules trough mitogen-activated protein (MAP) kinase like extracellular-regulated kinase 1 (ERK1) and ERK2 . Moreover, the role of MAP kinases on the modulation of gene expression depends on integrin engagement rather than simply on cell attachment . The increased expression of ITGB4 induced by 1 mM ethanol, we found, suggests a regulatory mechanism on the signal transduction pathways activated through ethanol.
The central role of ethanol on transcriptional regulation processes could be explained by the increased expression of COBRA1. The COBRA1 protein has been shown to be an integral subunit of the human negative transcription elongation factor . In addition, over-expression of COBRA1 represses the transcriptional activity of activating protein-1 (AP1) transcription factor [40]. Since ethanol-induced phosphorylation of protein kinases leads to an increased expression of transcription factors including AP1 [19], the effect of low concentration of ethanol on COBRA1 suggests a regulatory effect on transcription. Our data also demonstrated an increased expression of HMGN3. HMGN nuclear proteins bind specifically to nucleosomes, reduce the compactness of the chromatin fiber, and enhance transcription from chromatin templates . Interestingly, HMGN3 has been found to be associated with resistance against anticancer drugs including vinblastine, topotecan, paclitaxel and doxorubincin in human hepatocellular carcinoma derived cell lines . The resistance against anticancer drugs has been associated with the expression of transcription factors, such as NFκB and AP1 . These transcription factors are significantly over-expressed in ethanol-treated HepG2 cells, suggesting a role of ethanol-induced regulation on genes involved in transcriptional processes that could be applied to develop new strategies for the treatment of human hepatocellular carcinoma.
Our data also confirms the effect of low concentration of ethanol on genes involved in translational processes such as STAU2, a protein that facilitates the initiation of translation . Based on the increased expression of staufen proteins associated with Hepatitis C virus (HCV) infection , a leading cause of severe hepatitis that often develops into liver cirrhosis and hepatocellular carcinoma, the selective regulation of ethanol on STAU2 may represent an important target for future studies addressing the molecular mechanisms of ethanol on human hepatocellular carcinoma and requires further investigation.
Notably, the down-regulatory effect of 1mM ethanol concentration on ANK3 we observed, provides a potential therapeutic approach when considering the reported high expression of the ankyrin-repeat oncoprotein (gankyrin) in human hepatocellular carcinoma . Gankyrin binds to the cell-cycle regulator CDK4 and the S6b ATPase subunit of the regulatory component of the proteasome.
Based on the conserved gene expression profile in confluent HepG2 cells in vitro [21], the regulation of genes involved in transcriptional and translational processes we found suggests a potential therapeutic effect of ethanol at low concentration for the treatment of human hepatocellular carcinoma. However, it should be only considered for direct application into the tumor, known as percutaneous ethanol injection. The systemic application or the ingestion of ethanol induces a completely different pattern due to the reported ethanol-induced expression and activation of cytokines and chemokines in monocytes and macrophages (including Kupffer cells) [41, 42], and ethanol-induced mucosal injury in the upper gastrointestinal tract leading to increase in the permeability of the gut mucosa to endotoxins [43, 44]. These factors are involved in ethanol-induced liver damage. Thus, the direct injection of low concentration of ethanol for the treatment of hepatocellular carcinoma represents a promising alternative to improve the limitation of percutaneous ethanol injection, which is only indicated for small and single tumors [45, 46].
In conclusion, the functional genomics analysis presented in this investigation confirms the effect of ethanol at low concentration (1 mM) on the expression of genes involved in transcriptional and translational processes that are also associated with human hepatocellular carcinoma. These findings represent an important contribution toward the understanding of the molecular mechanisms of ethanol at low concentration in HepG2 cells, and a novel approach for the identification of potential targets in the diagnosis and treatment of human hepatocellular carcinoma.
We are grateful to Dr. Rolf K-H Kinne and Dr. Wolfgang Urfer for their valuable support.
The authors declare no conflict of interests.
1. Harries HM, Fletcher ST, Duggan CM. et al. The use of genomics technology to investigate gene expression changes in cultured human liver cells. Toxicol In Vitro. 2001 ;15:399-405
2. Hong Y, Muller UR, Lai F. Discriminating two classes of toxicants through expression analysis of HepG2 cells with DNA arrays. Toxicol In Vitro. 2003 ;17:85-92
3. Deaciuc IV, Arteel GE, Peng X. et al. Gene expression in the liver of rats fed alcohol by means of intragastric infusion. Alcohol. 2004 ;33:17-30
4. Deaciuc IV, Doherty DE, Burikhanov R. et al. Large-scale gene profiling of the liver in a mouse model of chronic, intragastric ethanol infusion. J Hepatol. 2004 ;40:219-27
5. Seth D, Leo MA, McGuinness PH. et al. Gene expression profiling of alcoholic liver disease in the baboon (Papio hamadryas) and human liver. Am J Pathol. 2003 ;163:2303-17
6. Brown PO, Botstein D. Exploring the new world of the genome with DNA microarrays. Nat Genet. 1999 ;21:33-7
7. Khan J, Saal LH, Bittner ML. et al. Expression profiling in cancer using cDNA microarrays. Electrophoresis. 1999 ;20:223-9
8. Lockhart DJ, Winzeler EA. Genomics, gene expression and DNA arrays. Nature. 2000 ;405:827-36
9. Gray NS, Wodicka L, Thunnissen AM. et al. Exploiting chemical libraries, structure, and genomics in the search for kinase inhibitors. Science. 1998 ;281:533-8
10. Fambrough D, McClure K, Kazlauskas A. et al. Diverse signaling pathways activated by growth factor receptors induce broadly overlapping, rather than independent, sets of genes. Cell. 1999 ;97:727-41
11. Tackels-Horne D, Goodman MD, Williams AJ. et al. Identification of differentially expressed genes in hepatocellular carcinoma and metastatic liver tumors by oligonucleotide expression profiling. Cancer. 2001 ;92:395-405
12. Zhang W, Morris QD, Chang R. et al. The functional landscape of mouse gene expression. J Biol. 2004 ;3:21
13. Kawai HF, Kaneko S, Honda M. et al. alpha-fetoprotein-producing hepatoma cell lines share common expression profiles of genes in various categories demonstrated by cDNA microarray analysis. Hepatology. 2001 ;33:676-91
14. Okabe H, Satoh S, Kato T. et al. Genome-wide analysis of gene expression in human hepatocellular carcinomas using cDNA microarray: identification of genes involved in viral carcinogenesis and tumor progression. Cancer Res. 2001 ;61:2129-37
15. Shirota Y, Kaneko S, Honda M. et al. Identification of differentially expressed genes in hepatocellular carcinoma with cDNA microarrays. Hepatology. 2001 ;33:832-40
16. Lee JS, Thorgeirsson SS. Functional and genomic implications of global gene expression profiles in cell lines from human hepatocellular cancer. Hepatology. 2002 ;35:1134-43
17. Lowichik A, Schneider NR, Tonk V. et al. Report of a complex karyotype in recurrent metastatic fibrolamellar hepatocellular carcinoma and a review of hepatocellular carcinoma cytogenetics. Cancer Genet Cytogenet. 1996 ;88:170-4
18. Zimonjic DB, Keck CL, Thorgeirsson SS. et al. Novel recurrent genetic imbalances in human hepatocellular carcinoma cell lines identified by comparative genomic hybridization. Hepatology. 1999 ;29:1208-14
19. Castaneda F, Rosin-Steiner S. Low concentration of ethanol induce apoptosis in HepG2 cells: role of various signal transduction pathways. Int J Med Sci. 2006 ;3:160-67
20. Richert L, Liguori MJ, Abadie C. et al. Gene expression in human hepatocytes in suspension after isolation is similar to the liver of origin, is not affected by hepatocyte cold storage and cryopreservation, but is strongly changed after hepatocyte plating. Drug Metab Dispos. 2006 ;34:870-9
21. Butura A, Johansson I, Nilsson K. et al. Differentiation of human hepatoma cells during confluence as revealed by gene expression profiling. Biochem Pharmacol. 2004 ;67:1249-58
22. Castaneda F, Kinne RKH. Effects of doxorubicin, mitomycin C, and ethanol on Hep-G2 cells in vitro. J Cancer Res Clin Oncol. 1999 ;125:1-8
23. Castaneda F, Kinne RKH. Short exposure to millimolar concentrations of ethanol induces apoptotic cell death in multicellular HepG2 spheroids. J Cancer Res Clin Oncol. 2000 ;126:305-10
24. Castaneda F, Kinne RK. Cytotoxicity of millimolar concentrations of ethanol on HepG2 human tumor cell line compared to normal rat hepatocytes in vitro. J Cancer Res Clin Oncol. 2000 ;126:503-10
25. Castaneda F, Kinne RKH. Ethanol treatment of hepatocellular carcinoma: high potentials of low concentrations. Cancer Biol Ther. 2004 ;3:430-33
26. Eisen MB, Spellman PT, Brown PO. et al. Cluster analysis and display of genome-wide expression patterns. Proc Natl Acad Sci. 1998 ;95:14863-8
27. Alizadeh AA, Eisen MB, Davis RE. et al. Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling. Nature. 2000 ;403:503-11
28. Bittner M, Meltzer P, Chen Y. et al. Molecular classification of cutaneous malignant melanoma by gene expression profiling. Nature. 2000 ;406:536-40
29. Lockhart DJ, Dong H, Byrne MC. et al. Expression monitoring by hybridization to high-density oligonucleotide arrays. Nature Biotechnology. 1996 ;14:1675-80
30. Bardag-Gorce F, French BA, Dedes J. et al. Gene expression patterns of the liver in response to alcohol: in vivo and in vitro models compared. Exp Mol Pathol. 2006 ;80:241-51
31. Dudoit S, Fridlyand J. A prediction-based resampling method for estimating the number of clusters in a dataset. Genome Biol. 2002 ;3:research0036
32. Dudoit S, Shaffer JP, Boldrick JC. Multiple Hypothesis Testing in Microarray Experiments. Statistical Science. 2003 ;18:71-103
33. Jung K, Quast K, Gannoun A. et al. A renewed approach to the nonparametric analysis of replicated microarray experiments. Biom J. 2006 ;48:245-54
34. Reiner A, Yekutieli D, Benjamini Y. Identifying differentially expressed genes using false discovery rate controlling procedures. Bioinformatics. 2003 ;19:368-75
35. Ashburner M, Ball CA, Blake JA. et al. Gene ontology: tool for the unification of biology. The Gene Ontology Consortium. Nat Genet. 2000 ;25:25-9
36. Kanehisa M, Goto S, Kawashima S. et al. The KEGG databases at GenomeNet. Nucleic Acids Res. 2002 ;30:42-6
37. Dahlquist KD, Salomonis N, Vranizan K. et al. GenMAPP, a new tool for viewing and analyzing microarray data on biological pathways. Nat Genet. 2002 ;31:19-20
38. Schaffert CS, Sorrell MF, Tuma DJ. Expression and cytoskeletal association of integrin subunits is selectively increased in rat perivenous hepatocytes after chronic ethanol administration. Alcohol Clin Exp Res. 2001 ;25:1749-57
39. Carloni V, Mazzocca A, Pantaleo P. et al. The integrin, alpha6beta1, is necessary for the matrix-dependent activation of FAK and MAP kinase and the migration of human hepatocarcinoma cells. Hepatology. 2001 ;34:42-9
40. Zhong H, Zhu J, Zhang H. et al. COBRA1 inhibits AP-1 transcriptional activity in transfected cells. Biochem Biophys Res Commun. 2004 ;325:568-73
41. McClain CJ, Barve S, Deaciuc I. et al. Cytokines in alcoholic liver disease. Seminars in Liver Disease. 1999 ;19:205-19
42. Jaeschke H, Gores GJ, Cederbaum AI. et al. Mechanisms of hepatotoxicity. Toxicological Sciences. 2002 ;65:166-76
43. Bode C, Bode JC. Activation of the innate immune system and alcoholic liver disease: effects of ethanol per se or enhanced intestinal translocation of bacterial toxins induced by ethanol?. Alcohol Clin Exp Res. 2005 ;29:166S-71S
44. Fukui H. Relation of endotoxin, endotoxin binding proteins and macrophages to severe alcoholic liver injury and multiple organ failure. Alcohol Clin Exp Res. 2005 ;29:172S-79S
45. Hsu C, Cheng JC, Cheng AL. Recent advances in non-surgical treatment for advanced hepatocellular carcinoma. J Formos Med Assoc. 2004 ;103:483-95
46. Lin XD, Lin LW. Local injection therapy for hepatocellular carcinoma. Hepatobiliary Pancreat Dis Int. 2006 ;5:16-21
Correspondence to: Francisco Castaneda, MD, Laboratory for Molecular Pathobiochemistry and Clinical Research, Max Planck Institute for Molecular Physiology, Otto-Hahn-Str. 11, 44227 Dortmund, Germany; Tel. 49-231-9742-6490, Fax. 49-231-133-2699, E-mail: francisco.castanedampg.de


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Within the scope of its competence as defined in Section 45§ of the CLV Consumer Protection Act of 1997, the National Association of Builders introduced the Information System of Complaint-free Construction Companies (BAR list of unprofessional construction companies) against the violations of the construction act.
ADAM-HOUSE Innovatív Kft. has obtained the Triple A (AAA) rating within the framework of and in accordance with the regulations of the Information System of Complaint-free Construction Companies. The managing director of our company guarantees in a statement that any legal dispute will be settled within the framework of a procedure before the Conciliation Board, and our company will accept the decision of the board, thus saving the customers from the need for lengthy and costly lawsuits.
Only 23.82% of the construction companies in Hungary are eligible for the Rating of Complaint-free Construction Company and as it creates the conditions for safety due to its objectivity, it is an excellent tool for distinguishing a reputable construction company. This is important because many new "trying" companies are emerging as a result of the temporary boom in the construction market, making it increasingly difficult to distinguish the companies with uncertain backgrounds from well-functioning and reliable ones.
Nomination in the Business Initiative Directions – in category GOLD
In 2018, our company was nominated for the Quality Award of the Business Initiative Directions, B.I.D. in the category GOLD.
What do we need to know about this organization?
The Business Initiative Directions, or B.I.D., was established in 1975 with the participation of 173 companies selected from many countries around the world. Its purpose is to recognize the companies and organizations that compulsorily recognize, introduce, and operate the quality principles of the Total Quality Culture announced by the B.I.D. The award was founded with the intention of drawing attention to the companies developed from own resources that have become known and recognized not only in their own country but also in other countries. An international committee decides on the receivers of the award based on recommendations or personal experience, as well as on international press coverage and market research data.
We are proud to be invited to an international event as the first original SIP house construction company of Hungary, and to be nominated for an award for our SIP technology, which is an innovation in Hungary. Our clear intention is for more and more people to get to know the original SIP technology though ADAM-HOUSE in Hungary. Our company only builds and designs houses with SIP systems, so we can say with confidence that we are professionals in this field! If you want an original SIP house, choose ADAM-HOUSE!
so that we can help you design your dream home and build it precisely! Fill in the form below and we will send you information with prices and a list of the things that the house will be equipped with!
I consent that ADAM-HOUSE Kft. is allowed to send me an email and I accept the contents of the Information on Data Management.

redpajama_set_name: RedPajamaCommonCrawl


text:
Pehlu Khan lynching case: Complaint of firing on witnesses fake, say Police
Jaipur | Published: October 3, 2018 5:54:55 PM
"No firing on the witnesses took place and the complaint was fake. There was no circumstantial evidence of firing and no such vehicle, as described by the complainant, is seen in CCTV footage," Circle Officer Behror Kushal Singh said.
The witnesses in the lynching case, including Khan's two sons, had alleged Saturday they were fired upon by unidentified men while they were on the way to appear in a court in Behror town. (File photo)
The Rajasthan Police claimed Wednesday they had found no evidence of firing on the witnesses of the Pehlu Khan lynching case and termed the complaint fake.
The witnesses in the lynching case, including Khan's two sons, had alleged Saturday they were fired upon by unidentified men while they were on the way to appear in a court in Behror town.
"No firing on the witnesses took place and the complaint was fake. There was no circumstantial evidence of firing and no such vehicle, as described by the complainant, is seen in CCTV footage," Circle Officer Behror Kushal Singh said.
"The complaint was posted on social media about the alleged incident but they did not inform the police control room. They went to the SP office instead of approaching a nearby police station which had raised doubts," he said.
Khan's son Irshad had lodged the complaint in the matter at the Neemrana Police Station.
Singh said the police will file a report in the court and legal action against the complainant will also be taken for filing a false complaint.
Six people, including Khan's sons Irshad and Arif and their lawyer, were on the way to court in Behror. They had alleged unidentified accused driving in an SUV without having registration number plate fired on them and fled from the spot.
On April 1 last year, Irshad and Arif were with their father in a pick-up truck when they, along with two others, were attacked by cow vigilantes in Alwar. They were on their way to Haryana reportedly after purchasing cattle in Rajasthan.
Khan, a 55-year-old dairy farmer, succumbed to his injuries two days later.


text:
Tag: Dallas Business Journal
Dallas Business Journal Writes
November 30, 2021 December 11, 2021 tpltblogger10 Comments
https://www.bizjournals.com/dallas/news/2021/11/30/texas-pacific-land-corporate-governance.html
The company said in a prepared statement to Dallas Business Journal that its classified board structure was recommended while still a trust by the Conversion Exploration Committee. The committee was made up of trustees and investors, most of whom became board members. "The structure is intended to provide stability and continuity to ensure a smooth transition from a trust structure to a c-corporation, and to enable TPL Corporation to attract and retain highly qualified directors who have a focus on the long-term objectives of the company," a Texas Pacific spokesperson said in a prepared statement to Business Journal.
Tim Schwartz, whose firm Schwartz Investment Counsel owns an almost-1% stake in Texas Pacific, said he was glad when the trust converted to a corporation. "I think that was a huge positive for the company," Schwartz said. "But since then, I would say there's been not as much progress as we would have hoped in terms of the corporate governance. And to us, it feels like the board is not that conducive to additional corporate governance improvements. The actions they've taken over the past few weeks, that just solidifies that opinion."
James Spindler, the University of Texas at Austin Mark L. Hart, Jr. Endowed Chair in Corporate and Securities Law and a professor at the McCombs School of Business, said implementing a classified board like Texas Pacific's can be controversial. Classified boards can entrench directors, protecting them from removal in hostile takeovers or proxy battles — like the one Texas Pacific faced two years ago.
"There's a general concern among reformers and activist investors, and I think in the larger corporate communities, that classified boards have some negative consequences," Spindler said. "(They) tend to entrench management. So if you have management that's making bad decisions, or making self-interested decisions, it's a lot harder to kick them out." Harvard Law School professors Alma Cohen and Director of the Program on Corporate Governance Lucian Bebchuk — experts on corporate governance — found through research that there's a correlation between classified boards and "an economically meaningful reduction in firm value."
Texas Lawbook / Dallas Business Journal
May 30, 2019 tpltblogger2 Comments
Texas Pacific Land Trust proxy litigation heats up with countersuit
But in the Oliver group's countersuit, they claimed the postponement of the meeting was only done when it became apparent that Oliver would win the election. They made public announcements that they would hold a meeting anyway, claiming they reserved the right to move forward with voting.
The dissident group held a shareholder meeting anyway on May 22 in Dallas on a different floor of the building Sidley's Dallas offices are located, where Oliver got elected.
The Oliver group argues in their countersuit that the law does not permit TPL nor its trustees to "adjourn, postpone, or otherwise delay a shareholder vote once the vote has been scheduled; only shareholders have that power."
They also called TPL's lawsuit, which was filed a day before the May 22 meeting, questionable, pointing out that the allegations TPL made in its lawsuit are hardly new.


text:
10 UAE tycoons among world's richest
Infrastructure development initiatives was one of the major drivers of capital into Dubai in 2014. (Shuttertsock)
Vicky Kapur
Published Tuesday, March 03, 2015
A record 10 UAE residents have made it to the Forbes' 2015 Billionaires List, with a combined net worth of a whopping $34.1 billion (Dh125 billion).
The US-based magazine today published its annual global billionaires' list, which shows that the number of billionaires in UAE has gone up from eight in 2014 to 10 in 2015, and the combined wealth that the UAE's billionaires have at their disposal has surged almost $10bn (Dh36bn) from $24.2bn (Dh88.8bn) last year.
Among the billionaires from the UAE, four are Emiratis and six Indians who've made the UAE their home.
#1 Abdulla bin Ahmad Al Ghurair & Family tops the UAE list, ranked at #220 globally (#305 in 2014), and with wealth estimated at $6.4bn (Dh23.5bn), a massive improvement over the $4.8bn (Dh17.61bn) they commanded last year.
Abdulla bin Ahmad Al Ghurair
"Abdulla Al Ghurair and his billionaire brother, Saif, are scions of a prominent UAE business family. In 1967 Abdulla founded Mashreqbank, now one of the country's leading banks. He remains chairman and his son Abdul Aziz is CEO," says his profile in the Forbes listing.
"The family holding company is run by an outsider, with the help of Abdulla's sons who oversee various divisions including food, construction, and real estate. Abdul Aziz heads the Family Business Network Gulf Cooperation Council, which aims to modernize family businesses, while ensuring they remain in family hands," it adds.
#2 At No. 2 in the UAE is Majid Al Futtaim, ranked #230 globally (#338 last year) and with a personal net worth of $6.2bn (Dh22.77bn). Majid Al Futtaim's wealth estimate too has improved by more than Dh5bn in one year, up from $4.5bn (Dh16.5bn) last year.
"Majid Al Futtaim is the brother of billionaire Abdulla Al Futtaim. Non-family members run his eponymous holding company, which operates malls and Carrefour hypermarkets across the Middle East, North Africa, and Central Asia.
"Michael Rake, the chairman of British telecom company BT Group, is chairman. Although privately held by Majid, it is the most transparent conglomerate in the UAE, raising capital on the financial markets and publishing its financials," states his Forbes profile.
#3 Rounding up the top 3 billionaires in the UAE is the Indian-born, Dubai-based Micky Jagtiani, who ranks #291 globally (#281 in 2014) whose current wealth is estimated at $5.2bn (Dh19bn) by Forbes, up from $5bn (Dh18.4bn) last year.
Micky Jagtiani
"Middle East retailing juggernaut, the Dubai-headquartered Landmark Group, was founded by Micky Jagtiani in 1973 with one store in Bahrain after his father and brother died. It generates $5 billion revenues annually from more than 1,900 stores across the Middle East, Africa and India," Forbes states in Jagtiani's profile.
"Landmark is stepping up expansion in fast food and restaurants through its food and beverage unit Foodmark, which has the Middle East franchise for Jamba Juice and Sweden's Max Burger, among much else. After ending a 2-year alliance with France's Groupe Auchan that operated 13 hypermarkets in India, Landmark teamed with Dutch retailer Spar. The privately held group, which wife Renuka helps him run, also has interests in hotels, healthcare, fitness gyms and confectionery," it adds.
#4 Saif Al Ghurair, whose brother ranks No. 1 among UAE's richest, is at No. 4 in the country and #512 globally (#609 last year). His net worth is estimated at $3.4bn (Dh12.5bn) by Forbes, up from $2.8bn (Dh10.3bn) last year.
Saif Al Ghurair
"Saif Al Ghurair is the former chairman of family holding company Al Ghurair Group. He and his brother Abdulla, also a billionaire, are scions of an old Dubai merchant family. Six of Saif's sons hold positions within the group, which has interests in banking, steel, and plastics for food packaging. Abdulrahman is chairman and Majid is chief executive. Saif is also a major shareholder in Mashreq, a leading Emirati bank run by his nephew, Abdul Aziz Al Ghurair," lists his Forbes profile.
#5 Ranked at No. 5 among the UAE's richest is Abdulla Al Futtaim (#557 globally, #687 last year), with his current wealth estimates at $3.2bn (Dh11.8bn), up from $2.5bn (Dh9.2bn) last year.
Abdulla Al Futtaim
"Abdulla Al Futtaim owns conglomerate Al Futtaim Group, which is run by his son Omar. It is the exclusive distributor of Toyota and Honda vehicles in the UAE, and sells Toyotas in Egypt. In addition to its automotive business, Al Futtaim owns the franchises for Ikea, Toys 'R' Us, and Marks & Spencer, which anchor its real estate projects, such as the urban community of Dubai Festival City, and the newly opened Cairo Festival City. Al Futtaim is the brother of Majid, also a billionaire," his Forbes profile notes.
#6 At No. 6 among the UAE's richest people is Indian-born and Abu Dhabi-based M.A. Yusuff Ali with a net worth of $2.5bn (Dh9.2bn), up from last year's $1.8bn (Dh6.6bn). He is ranked #737 globally (#988 last year).
Yusuff Ali
"Indian-born retail king of Abu Dhabi, MA Yusuff Ali controls the $5.8 billion (revenues) LuLu Group, which has 114 hypermarkets, supermarkets and grocery outlets, mostly in the Middle East. It has lately expanded into Malaysia and Indonesia where its 'halal' products are popular," says his profile.
"Yusuff Ali, who hails from a village in the southern Indian state of Kerala, is pumping investments back home. He already has a LuLu mall and two Marriott hotels in the southern Indian city of Cochin where he maintains a 60,000-square- foot waterfront home. He's now building a technology park called the Lulu Tech Park and a Grand Hyatt hotel," it adds.
"Recently he announced that he will invest $435 million in the southern state of Telangana which will include a mall, hypermarket, food and meat processing unit and a convention centre. New toys include an Embraer Legacy 500 jet."
#7 Following him at No. 7 in the UAE is Dubai-based real estate tycoon Ravi Pillai, with a net worth of $2.4bn ().He is ranked #782 globally (#988 last year).
Ravi Pillai Source: By Rpgroup - Licensed under CC0 via Wikimedia Commons
"India-born, Middle East construction tycoon Ravi Pillai controls the $3.5 billion RP Group whose flagship is Nasser Al-Hajri Corp., a construction heavyweight in Saudi Arabia. He owns a 50 per cent stake in the privately held firm, which is named after his local partner," says his profile.
"Pillai is bullish on Dubai, where he's lined up real estate projects worth $1.5 billion. These include a Crowne Plaza hotel due to open in 2016 and a 110-story tower that will be Dubai's second tallest. His fortune is up partly on new information on his Indian assets, which include stakes in banks, hotels, property. He visits the Guruvayur temple in his native Kerala state every month because, he tells Forbes, 'When you're doing so much you need blessings.'"
#8 Education czar Sunny Varkey is ranked at No. 8 in the UAE and #949 globally (#988 last year). The net worth of the founder of the world's largest KG-to-Grade 12 school operator is estimated by Forbes at $2bn (Dh7.4bn), up from $1.8bn (Dh6.6bn) last year.
Sunny Varkey
"Son of expat teachers, Sunny Varkey created Gems Education, the largest operator of private kindergarten- to-grade-12 schools in the world, with 50 schools and 140,000 students across the Middle East, Africa, Europe, Asia and North America. In October, he sold a 20 per cent stake for an estimated $350 million in its emerging markets business, covering the Middle East, North Africa and East Asia to a consortium of investors which included Blackstone and Bahrain's sovereign investment arm," notes his profile.
"Varkey stepped down as chairman, ceding spot to Sir Michael Peat, a former private secretary to Prince Charles. While Gems' first school in the US has opened in Chicago, a plan to start a school in New York has been stalled by a lawsuit by a property developer who alleged that Gems breached a tenancy contract. Passionate about fitness, Varkey works out daily. Dotes on his four grandkids."
#9 At No. 9 in the UAE is another self-made Indian expat BR Shetty, who has interests in healthcare and foreign exchange remittances. With a net worth of $1.7bn (Dh6.2bn), Shetty ranks at #1118 globally (#1565 last year).
BR Shetty
"Former pharma salesman B.R. Shetty immigrated to Abu Dhabi in 1972. He made a big splash last May with the acquisition of UK foreign exchange group Travelex Holdings for an estimated $1.6 billion together with Centurion, the investment arm of Saeed Bin Butti Al Qabaisi, his longtime business partner," lists his profile.
"Shetty already owns the UAE Exchange, which handles over 10 per cent of all inward foreign remittances into India. His London-listed NMC Health is the UAE's largest private health care firm. Other interests include generics firm Neopharma which is a contract manufacturer for Pfizer and Merck Serono. Shetty also owns prized real estate such as an apartment on the 100th floor of Dubai's Burj Khalifa, the world's tallest building. He offered jobs at NMC to 46 Indian nurses who were stranded in Iraq's Tikrit after militants seized it."
#10 Rounding up the UAE's representation among the world's billionaires is Azad Moopen, with a net worth of $1.1bn (Dh4bn). He is ranked at #1638 globally.
Dr Azad Moopen
"Physician Azad Moopen founded and chairs Dubai-based Aster DM Healthcare, a leading health care provider in the Middle East and India. He was a professor at a government-owned medical college in Calicut in south India before he immigrated to Dubai in 1987, where he set up his medical practice," his profile says.
"Moopen went on to build a healthcare empire that today treats more than 8 million patients annually, employs over 1,000 doctors and covers the spectrum of hospitals, medical clinics, diagnostic centers, pharmacies and a health care consultancy. He's reportedly planning to list Aster in India. Passionate about reversing the brain drain from India, he has built hospitals and a medical college in his native Kerala state.Sets aside one-fifth of his income for philanthropy every year."
UAE's richest among the World's Top Billionaires
#220 Abdulla bin Ahmad Al Ghurair $6.4bn
#230 Majid Al Futtaim $6.2bn
#291 Micky Jagtiani $5.2bn
#512 Saif Al Ghurair $3.4bn
#557 Abdulla Al Futtaim $3.2bn
#737 MA Yusuff Ali $2.5bn
#782 Ravi Pillai $2.4bn
#949 Sunny Varkey $2bn
#1118 BR Shetty $1.7bn
#1638 Azad Moopen $1.1bn


This week two programs already were changed to "NOT PAYING" status. Some might say it's not a surprise. However, we all know that from time to time there are programs that satisfy investors for a few months. Even though there might be some patterns, we can't predict the future of any program being monitored and it's totally up to each one of us where and when to invest. As usual, a few HYIP's turn into scam and a few new ones join the game.
Today my first review is a program called Crypteiro, which has a Telegram-bot based investor panel. It joined Golden Stage on DavidNews.com monitor 8 days ago an has been online in total for 14 days. I have now reinvested in this program $400 and will keep you updated with the payment status, which on the 6th of February is "PAYING". I have already opened the website of Crypteiro and must say the first impression of this program is very good. However, let's take a better look at this program and find out more about it!
Crypteiro is offering two investment plans – "Depository" with 20% net revenue within 15 days and "Savings account" with 5-15% net revenue per month. Minimum deposit of both investment plans is $50 and minimum withdrawal is $1. Accruals are available every 3 hours in the "Depository" plan, but every hour in the "Savings account" plan. You can already see that the first plan is more beneficial because deposit can generate 20% net revenue per 15 days while the second only 2,5-7,5%. Probably admin is trying to diversify the cash flow here. Due to unpredictable nature of HYIP's the first plan has a higher chance of attracting potential investors. Minimum deposit and withdrawals are similar for both investment plans and the initial deposit is included in the payments.
On Crypteiro "About Us" page we can read the whole story of this program. One thing is clear to me that by investing in Crypteiro we "get the share of profit". Everything else is written using codenames and abstract technological terms. Admin has come up with a unique cryptocurrency called EIRO, which I couldn't find online. Some sort of neural networks regulates the cost of this currency. Feel free to do some extra reading if you are interested. In other words, Crypteiro is a crypto-currency inspired program and it has UK company registration certificate.
The website is very simple but looks professional. There are 10 language options available but only 9 of them are active. Feel free to check if translations are bot translated. As I said, the website gives a good impression. First, I would say that designer has chosen a good combination of colors. Second, right after opening the homepage we can information about investment plans. Third, real-time statistics gives the impression that program is very active. In fact, there is much going in the real-time feed. Yes, we should be skeptical about stats, but the deposited and withdrawn amounts I have seen so far from this feed look realistic if compared to feeds I see on other websites, which don't change and show only large deposits.
Crypterio has been active on social media since the 16th of January. In total 27 likes on the FB community page without many reactions on posts. However, community page looks realistic for 2 weeks old program. Twitter – 9 followers, Vkontakte – 170. In fact, Vkontakte profile is very active and has more posts than previous two. This might be an explanation of the higher total amount of visitors. I did also check what's going on in the HYIP community forums and I see mainly information about deposits and withdrawals. Sure, this impression might also be the result of marketing activities.
In case you are not familiar with telegram-bot type investor panels, I can say they are very simple. In fact, I prefer them over some custom-made panels. Custom-made panels are often very functional and interactive but most of them are hard to navigate. In fact, some of them seem to be built to confuse us and make it hard to understand how to make withdrawals. Of course, there are no problems with deposits and they are always on the first dashboard, but withdrawals… As I said, Crypteiro telegram bot is very simple and it actually tells you what to do in case of adding deposit or withdrawing money. Just follow the instructions and enter the information bot requests. So far no problems with bot or withdrawals.
I already gave you insight into investment plans. Crypteiro is offering one simple investment plan with 20% net profit within 15 days. It's a short-term investment with accruals available every 3 hours. Initial deposit is included in the payments. Minimum deposit in Crypteiro is $50 and minimum withdrawal $1. So, at first glance, it might be confusing to read 1% every 3 hours and 20% revenue in 15 days. 20% is net revenue, but 1% includes both initial deposit and the profit. $200 investment in this plan would reach its break-even point after 13 days. The last two days is when deposit makes the actual 20% profit.
To sum it up for you the net profit of the first plan is 1,33% a day, which puts this program into short-term deposit category with low rates. However, I assume such rate looks realistic at least for a few investment cycles. In fact, the first investment cycle will complete tomorrow. Currently, the website, the overall marketing approach, telegram bot and other features look smooth but we don't know what will happen tomorrow with this or any other program on DavidNews.com monitor. Therefore, if you ever decide to make any investments, don't invest more than you can afford to lose!
Have you already made an investment in Crypteiro and have any useful information to share with us? Please drop a message in the chat box to share your experience!
Investment plans: 1% every 3 hours for 15 days, initial deposit included in the payments.
Invest in Ethereum on eToro the World's #1 Social Trading Network.


text:
package org.usfirst.frc.team2549.robot.subsystems;

import org.usfirst.frc.team2549.robot.RobotMap;
import org.usfirst.frc.team2549.robot.commands.ShooterCommand;

import edu.wpi.first.wpilibj.ADXL345_I2C;
import edu.wpi.first.wpilibj.AnalogGyro;
import edu.wpi.first.wpilibj.AnalogPotentiometer;
import edu.wpi.first.wpilibj.Compressor;
import edu.wpi.first.wpilibj.DigitalInput;
import edu.wpi.first.wpilibj.DoubleSolenoid;
import edu.wpi.first.wpilibj.SpeedController;
import edu.wpi.first.wpilibj.command.Subsystem;
import edu.wpi.first.wpilibj.interfaces.Potentiometer;

public class ShooterSubsystem extends Subsystem {
	private SpeedController liftController;
	private SpeedController wheelController;

	private AnalogGyro liftGyro;

	private DigitalInput limitSwitch;

	private double offset = 0.;

	public ShooterSubsystem(){
		liftController=RobotMap.liftMotor.getController();
		wheelController=RobotMap.wheelMotor.getController();

		liftGyro = new AnalogGyro(RobotMap.liftGyroPort);
		liftGyro.reset();
		liftGyro.setSensitivity(0.007);

		limitSwitch = new DigitalInput(RobotMap.limitSwitch);
	}

	public boolean getLimitSwitchValue(){
		return !limitSwitch.get();
	}

	protected void initDefaultCommand() {
//		setDefaultCommand(new ShooterCommand());
	}

	public void setLifter(double value){
		liftController.set(value);
	}

	public void setWheels(double value){
		wheelController.set(value);
	}

	public double getRawAngle(){
		return liftGyro.getAngle();
	}

	public double getAngle(){
		return getRawAngle()-offset;
	}

	public double getGyroOffset(){
		return offset;
	}

	public void resetGyro(){
		offset=getRawAngle();
	}
}

redpajama_set_name: RedPajamaGithub


text:
footer {
    background: url(../../images/work.jpg) no-repeat fixed left center / cover rgba(0, 0, 0, 0);
    color: #fff;
    font-size: 16px;
    width: 100%;
}


Hardcover, 5 x 7.5 in. / 104 pgs / 75 color.
From the 18th century to the 21st, the Royal Academy of Arts in London has occupied a prominent, sometimes controversial and always individual position in the art world. Its Annual Exhibitions, now known as the Summer Exhibitions, have seen artistic reputations rise and fall, and its enduringly popular international loan exhibitions have helped to shape the public's appreciation of the visual arts.
As it celebrates its 250th year, the Academy continues to be run by artists. Packed with illustrations, this concise introduction to the Academy's 250-year story considers the people, places and events that have made the Academy such a unique institution.
FORMAT: Hbk, 5 x 7.5 in. / 104 pgs / 75 color.


text:
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The most comprehensive one-volume selection of Jefferson ever published, all in a handsome, 1,600-page edition. Includes more than 250 letters, his Autobiography, and public writings about politics, education, science, botany and gardening, religion, literature, architecture, the habits of his fellow citizens, and his beloved home, Monticello.
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text:
In opening remarks, presiding officers urge church to take risks, soul search
By Tracy Sukraw
Posted Jun 24, 2015
The church's journey ahead "requires courage – to venture into the unknown future, to befriend strangers, to confront whatever denies life and liveliness, and to keep learning interdependent ways of living," Presiding Bishop Katharine Jefferts Schori tells a joint session of the House of Deputies and House of Bishops on June 24, the day before General Convention's official start. The horse balloon floats above the Diocese of Lexington's deputation table. Photo: Mary Frances Schjonberg/Episcopal News Service
Editor's note: On-demand video of the presiding officers' remarks can be accessed by clicking here.
[Episcopal News Service – Salt Lake City] Deputies and bishops gathered in the Salt Palace Convention Center for a joint session the morning of June 24 to hear opening remarks from Presiding Bishop Katharine Jefferts Schori and House of Deputies President the Rev. Gay Clark Jennings.
The joint session, coming a day before the General Convention's legislative business officially begins on June 25, set a collaborative context for the work ahead.
With all that General Convention has to accomplish over the next nine days, both Jefferts Schori and Jennings focused on The Episcopal Church's need to cross boundaries into new frontiers, even as it focuses on its institutional structure and governance.
They urged risk taking, soul searching, courage and openness in the enterprise.
Jefferts Schori described The Episcopal Church's trek as "a missionary expedition," using a space exploration analogy that played off the TREC acronym for the Task Force for Reimagining the Episcopal Church, whose restructuring proposals are a high-profile topic coming before General Convention.
"There is abundant adventure ahead on this heavenward trek, and it asks our courage to engage unknown beings, new challenges and unexpected opportunities," Jefferts Schori said. "We're bound for the galaxy called Galilee and the edges of the known world, because that's where Jesus sent us and that's where he promises to meet us."
She emphasized interdependence as the church's vocation and destiny.
"No one goes alone; together we care for those most in need. Our growing understanding of human interrelationship with the rest of creation means conscious care for the earth and all its inhabitants, not just the human ones," she said.
She acknowledged "plenty of challenge ahead" for General Convention, and said that the decisions made in Salt Lake City "can help to build a more just and peaceful world," she said.
"This body is meant to be a sacrament of God, an outward demonstration of the life and hope within us," she said.
"We are on a missionary expedition, scattering seeds of life and love to the winds and across the earth. There is abundant risk in such profligate sowing, for not all will take root and grow to harvest," Jefferts Schori said, but nonetheless urged the church toward new ways of being and reaching out.
"How will this body here in Salt Lake continue to foster that kind of sowing?" she asked.
The text of the presiding bishop's remarks is here.
House of Deputies President the Rev. Gay Clark Jennings reminded the June 24 joint session of the House of Deputies and House of Bishops that both houses have a lot of work ahead of them before General Convention's July 3 adjournment. "Not just meetings and hearings and legislative sessions, but also listening to each other and paying attention to what new things are arising among us," she said. "Much of the work we have to do is about our own institutional future. But that's not all of what we do." Photo: Mary Frances Schjonberg/Episcopal News Service
Jennings, too, referenced how the church finds itself "standing on a boundary between the old and the new."
"Gathering here to wrestle with the future of our beloved Episcopal Church, we are standing on holy ground, straining to hear God speaking above all the noise," she said.
In preparation for the work ahead, "let's quiet the din around us and listen for the new within ourselves," she said, referencing a sermon by theologian Paul Tillich.
"Let's turn down the volume on the Pew Center's statistics about the decline of the institutional church, the endless online arguments about what millennials really want and what one tweeter recently called the 'church decline industrial complex.' Let's quiet our souls," Jennings said.
The church's debate about what form its structure should take to enable mission is really about identity, she said.
"We're talking about our vision of the beloved community, and we are asking important questions. Can we restructure in a way that inspires and energizes the people of our church? Can we restructure in a way that continues to respect the gifts of all orders of ministry? We are talking about who we are as the people of God if we are not the church we have always been," she said. "We're talking about the fact that God isn't done with us yet."
Wrestling with issues of the church's institutional future is not the only work ahead, she reminded the gathering.
"The church isn't the only segment of our society that's reeling right now," Jennings said. "Income inequality is greater than it has been since 1928, our cities are besieged by gun violence and racial injustice, and too many young black men are caught in the school-to-prison pipeline."
"This summer, especially, we must repent" of not doing enough "to right the wrongs of discrimination, white privilege and inequality in the world around us," Jennings said.
"General Convention is where we Episcopalians have the ability not only to proclaim that black lives matter, but also to take concrete action toward ending racism and achieving God's dream of racial reconciliation and justice. We can do no less," she said.
The text of Jennings' remarks is here.
The June 24 joint session of the House of Deputies and House of Bishops met in the cavernous House of Deputies hall, which has enough space for close to 900 deputies and alternates, translators, a visitor gallery and space for media, international and other invited guests, and Executive Council members. Photo: Mary Frances Schjonberg/Episcopal News Service
The joint session also heard from the Rev. Nancy Crawford, the president of the Executive Board of Episcopal Church Women, whose triennial meeting is held concurrently with General Convention.
She reported on several ECW social justice efforts, including work over the past triennium to raise awareness of human trafficking — through support of Girls Educational & Mentoring Services, or GEMS, an education and mentoring service provider for girls and young women who have experienced sexual exploitation; support this year for the Homeless Youth Resource Center in Salt Lake City; and the ECW's Women to Women project, which provides small micro-enterprise grants to women around the world.
— Tracy J. Sukraw is part of the Episcopal News Service team covering convention.
General Convention 2015,
President of the House of Deputies,
Presiding Bishop Katharine Jefferts Schori


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Home » Sports » Soccer
Platini urges fans to make it a memorable final in Rome
UEFA President Michel Platini appealed to Manchester United and Barcelona fans to turn tonight's UEFA Champions League final into a soccer festival and not tarnish the event with violence.
More than 40,000 fans with tickets from England and Spain are expected in Rome and UEFA has organized fan zones for both sets of supporters as well as a festival site. However, several thousand fans, especially from England, are expected to arrive without tickets, and they are causing UEFA some concern.
Worst desecration
Platini, who experienced the worst desecration of European soccer's showpiece event as a Juventus player in the 1985 final after the Heysel Stadium disaster in which 39 Juventus fans were killed, said UEFA had every confidence the "dream final" between two of European soccer's most glamorous clubs would go ahead without trouble, even though UEFA is aware of the possibility it could occur.
"This is going to be a wonderful match, and the whole world will be glued to this event, that is why it is important that everyone behaves themselves," Platini said.
"Football must show itself in the best positive light. UEFA is at the service of the fans, as was the case last year with waiving the visas for Moscow and will be the case this year, as we have done everything possible to make sure that they can enjoy the atmosphere, the event and the celebration of football.
"We are therefore counting on the fans to have a good time and to behave. Enjoy Rome, enjoy the festivities and most of all enjoy the football."
UEFA has worked with the Italian police and security services over the last two years to ensure that the match goes ahead without trouble.
"We are fully aware there is a history of incidents in Rome caused by the rogue elements among some fans in the city, but we are not aware of any issues between Barcelona and Manchester United fans and we are expecting them to really enjoy the match in one of the world's greatest cities," Rob Faulkner, UEFA's head of communications, said.
"One area that does concern us is the large number of ticketless fans ... We are asking the fans with tickets to make their way to the stadium early and to be well-prepared and we are asking fans without tickets not to travel."
UEFA had threatened to take the final away from Rome if AS Roma's Champions League quarterfinal against United last season was marred by the sort of violence that occurred on United's previous two visits to the city.
That did not happen but Arsenal fans were attacked before its team knocked out Roma in a last-16 second leg match in March.


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James Chrobocinski has been a licensed real estate broker since 2004. He obtained his real estate license in Corpus Christi, Texas and a few years later became the owner of the Padre Island branch of Corpus Christi Realty Group.
James' spent 26 years in Corpus Christi, Texas. He moved there from Los Alamos with his father Tom Chrobocinski after junior high school. He decided it was time to return home after losing his mother in February 2012 and his grandmother in 2010. After returning to Los Alamos, James became a qualifying broker and the owner of Zia Realty Group.
In January, he purchased the real estate division of REA from Pearl White and a short time later purchased Los Alamos Properties from David Horpedahl. He has since opened an office Santa Fe and Pojoaque and plans to grow Zia Realty Group throughout the state within the next seven years.
James has deep ties to Los Alamos. His grandfather and namesake James Bramble, 93, has lived in Los Alamos since the Manhattan Project era of the 1940s. His Grandmother Pat Bramble died in March of 2010.James' stepfather John Foster works at Los Alamos National Laboratory and his brother Randy Chrobocinski Foster is a Santa Fe sheriff married to local veterinarian Shayna Whitaker. James' sister is Jennifer Foster King who is the physician market manager for Los Alamos Medical Center. James' younger brother is Joe Foster who works in IT at LANL and his wife Erica is a nurse at Presbyterian Health Services in Espanola. James' uncle Bill Bramble graduated from Los Alamos High School. Chrobocinski's mother Jeannie Bramble Foster also graduated from Los Alamos High School. She worked many years as a registered nurse in Los Alamos and real estate broker for well-known broker Pat Rogers.
James earned his nursing license and went on to work in healthcare management for 15 years. He met his wife Jacqueline while working in a large hospital in Corpus Christi. The Chrobocinski's married nine years ago and have a son JJ, 7, who attends Mountain Elementary School.
Chrobocinski is a member of the Rotary Club of Los Alamos and serves as president of Los Alamos Little League.


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Sarah Dekker (born 8 March 2001) is a Dutch female handball player who plays for German club HSG Bensheim/Auerbach.

She also represented Netherlands in the 2019 Women's U-19 European Handball Championship, were she received silver.

Achievements
Junior European Championship:
Silver Medalist: 2019

References

2001 births
Living people
Dutch female handball players
21st-century Dutch women

redpajama_set_name: RedPajamaWikipedia


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Automotive News Europe
PSA will build 508, compact sedan in India
PARIS -- PSA/Peugeot-Citroen will invest 650 million euros ($929 million) to build a plant in India with capacity to produce 170,000 vehicles a year.
PSA will assemble two cars, a new compact sedan and the Peugeot 508 mid-size model, at the plant in the state of Gujarat starting in 2014.
"The compact car category corresponds closely to the needs of India's emerging middle class," PSA spokesman Pierre-Olivier Salmon said.
PSA CEO Philippe Varin is looking to add factories in India and China in an effort to reduce the automaker's dependence on the slower-growing European market.
The plant investment deal includes options for future expansion, PSA said. The carmaker will start importing the 508 to India before the new facility comes on stream, Salmon said, without giving a more precise date.
PSA suspended a project to build a plant near Hyderabad, India, 18 months ago pending the outcome of tie-up talks with Mitsubishi Motors Corp. Negotiations between the French and Japanese carmakers ended without a deal last year.


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Scotland's History Mapped Out
Collections, Digital
Written by: Peigi MacKillop
Wed 4 April 2018
Big changes to our PastMap website are making it even easier to search Scotland's historic sites and landscapes
After 6 weeks of being tried, tweaked and tried again by our intrepid testers, the new version of PastMap is now live!
With several new and enhanced features, this updated version of our digital resource for searching Scotland's archaeology, architecture and landscapes is definitely worth investigating.
What is PastMap?
PastMap shows you information about historic sites and landscapes all over Scotland, brought together on maps spanning from 1843 to the modern day. Historic sites available on PastMap include locations of battles, historic buildings, and places related to maritime history like shipwrecks.
The website gathers information from our Listed Buildings and Scheduled Monuments records, the HES Archives available on Canmore and from many Local Historic Environment Records. Through PastMap, all these records are available in a single place.
Explore the past – wherever you are
In our upgrade, we've made PastMap fully mobile responsive. Wherever you have a wifi or 3G signal, you can use the website to look for historic sites around you.
Even more maps
You can now choose from eight different background maps. These include historic Ordnance Survey (OS) layers courtesy of our colleagues at the National Library of Scotland. Historic maps range from OS 1st editions from the mid-late 1800s through to the early 1960s.
The Royal Burgh of Tain on the 1st edition OS map showing the conservation area (blue), listed buildings (red) and Local Authority records (yellow)
With our update, you can also now investigate PastMap records on four different types of modern map:
Ordnance Survey Licensed Data (OSMA)
Ordnance Survey open data (colour and Black and White)
OpenStreetMap.
OSMA includes MasterMap, the most comprehensive map of the UK.
A bird's eye view
PastMap now includes aerial photography, so you can overlay site records onto a bird's eye image of your area. This is useful for showing landscape features that are difficult to see on a map, such as cropmarks and earthworks.
These archaeological features are most visible when viewed from above. Through aerial photography, it's possible to identify signs of past human activity that usually can't be seen from ground-level.
Kirkcudbright from the air, showing the town's two castles (orange – Scheduled Monuments), Local Authority records (yellow) and Canmore records (green dots)
More data for you to download
PastMap offers a take-away data service. This means you can download up to 1,000 records for your own research. This can go straight into a spreadsheet or into a GIS package, which is a way to digitally map out geographic data. If you want to see PastMap records in Google Earth, you can download them as a KML file. These file types can also be read by QGIS, a popular free GIS package.
There are thousands of site records on PastMap, and it's easy to view an area that has lots of sites one on top of another. For example, a listed building may also be in a conservation area. Now, PastMap can list details of stacks of sites all at once, and it displays a handy pin that reminds you where you clicked or tapped – essential in built up areas!
The final say
Here is what some of our beta-testers have said so far:
Very nice beta version of past map.
The aerial photography background is also really good too.
The whole concept of the idea is really good.
I love the new map compared to the old PastMap – much better experience!
We hope you enjoy new PastMap. Let us know what you think; we welcome your feedback!
Peigi MacKillop
Peigi MacKillop is a Web Projects Manager in our Information Systems team. Her interests include usability testing and user experience. She also has an enthusiasm for life in the Outer Hebrides, particularly in the lives people led in Black Houses, and runs a small Gaelic lunch club at John Sinclair House. View all posts by Peigi MacKillop
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That looks brilliant !


Ubisoft Forums > Rainbow Six: Siege > Technical Issues > PC > I didn't get my 600 blue credits for buying the game please help!
View Full Version : I didn't get my 600 blue credits for buying the game please help!
I played on the free weekend and decided I really like this game. So I buy it while keeping the r6 browser open. My friends said when they got the game they got enough blue credits for one DLC character, but I didn't.
I am sorry to hear that you did not receive any Rainbow Six Siege credits. If you purchased the starter edition you should have received 600 credits.
If this was the edition you purchased can you please submit a support ticket (https://support.ubi.com/en-gb/Cases/new) and attach your proof of purchase for the game and our Customer Support team will assist you further.


text:
UncategorizedNewsDance Today – NewsFeaturesClassifiedsDance Today – BlogPast IssuesAdvertisingInterviewsReviewsBlogAuditionsSituations VacantFeaturedHome Page Featured ItemStrictly SpeakingThe Lowe DownLondon DuendeTravels with my danceA summer like no otherA dance image a dayThink about ThisTalking danceFeatured SchoolsFeatured ProductsScotlandNorth WestNorth EastWalesMidlandsEastern EnglandSouth WestSouth EastNorthern IrelandEuropeRest of worldLog-in from LondonBloch's blog
Autumn at Sadler's Wells
A Scandinavian season, a collaboration between composer Thomas Adès and choreographers Karole Armitage, Wayne McGregor, Crystal Pite and Alexander Whitley and a new work by Akram Khan and flamenco star Israel Galván (pictured) are among the highlights of the autumn season at London dance venue Sadler's Wells.
Kevin O'Hare on the 2014–15 Linbury season
In recent years, The Royal Ballet has had a bigger hand in the dance programme of the Linbury Studio Theatre, from commissioning new works from other companies to giving its own performances there. Kevin O'Hare, the artistic director of The Royal Ballet, talks about the Linbury season.
UPDATE: Osipova concussed during performance
Natalia Osipova was injured while dancing the matinée performance Wayne McGregor's new ballet Tetractys – The Art of Fugue on Saturday, February 8. With Osipova injured, and fellow cast member Thiago Soares unwell, The Royal Ballet was forced to cancel the evening performance of the work.
Vadim Muntagirov to join The Royal Ballet
Vadim Muntagirov is leaving English National Ballet to join The Royal Ballet. Muntagirov trained at The Royal Ballet School but joined English National Ballet, where he was promoted very early, and developed an outstanding partnership with ballerina Daria Klimentová. Recently, two Royal Ballet ballerinas had joined ENB: Tamara Rojo, now artistic director of ENB, and […]
FULL REPORT: National Dance Awards 2013
The winners of the 14th Critics' Circle National Dance Awards (NDA), held on Monday, January 27 at The Place in London, described everything from the joy of dance to the need to pretty much kill yourself in performance. Decided by the Dance Section of the Critics' Circle, the awards recognise performances given between September 1, […]
Dance on television this Christmas
Dance on television this Christmas Christmas is here! Along with mince pies, frantic shopping and The Nutcracker on stage, there's also plenty of festive television. Dancing Times has been circling the dance goodies in our Christmas listings magazine, with everything from the sequins of Strictly Come Dancing – both the series finale and the Christmas special (pictured) – […]
Dance at the London Coliseum
The London Coliseum will have a busy spring season for dance, with stars and companies including Ivan Putrov, the Kings of the Dance, Les Ballets de Monte Carlo and Eifman Ballet.
Men in Motion at the London Coliseum
Men in Motion, Ivan Putrov's showcase of male dancing, comes to the London Coliseum from January 30 to 31.
National Dance Awards: nominations announced
Nominations for the 14th National Dance Awards were announced today by the dance section of the Critics' Circle.
Matthew Golding to join The Royal Ballet
Matthew Golding, currently a principal dancer with Dutch National Ballet, is to join The Royal Ballet in February 2014. His first performance will be on March 27, when he will partner Natalia Osipova in The Sleeping Beauty.
Gala for Yorkshire Ballet Summer School
STOP PRESS – Sergei Polunin will also be appearing at the Gala Anthony Dowell and actor Derek Jacobi will host a gala marking the 40th anniversary of the Yorkshire Ballet Summer School (YBSS), held at Sadler's Wells on September 29.
David Wall
David Wall, one of the UK's greatest male dancers, died on June 18, 2013. Kevin O'Hare, director of The Royal Ballet, and Tamara Rojo, director of English National Ballet, have led tributes to Wall as a dancer, teacher and coach.


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Q: pytest test duration with class setup We have some performance test infrastructure built with python and pytest. One of our test classes must restore a database backup in the class set up, then run all of the tests. The problem is the test duration, we want to be able to track the duration of each test method over time. However, the duration of the database restore in the class set up is included in the duration of the first test that runs.
@classmethod
def setUpClass(cls):
    TestHelper.restore_database_backup(...)

def test_carbon_udp(self):
    ...

This is the results we see in Jenkins:

The test itself takes about 13 mins, whereas the db restore is about 40 mins. I don't care how long the restore takes, I'm just concerned about the test duration. Is there any way to run the tests in this way, where the setUpClass method duration is not included in the duration of the first test? Thanks.

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