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Sequencing of neuroblastoma identifies chromothripsis and defects in neuritogenesis genes
Neuroblastoma is a childhood tumour of the peripheral sympathetic nervous system. The pathogenesis has for a long time been quite enigmatic, as only very few gene defects were identified in this often lethal tumour1. Frequently detected gene alterations are limited to MYCN amplification (20%) and ALK activations (7%)2, 3, 4, 5. Here we present a whole genome sequence analysis of 87 neuroblastoma of all stages. Few recurrent amino acid changing mutations were found. In contrast, analysis of structural defects identified a local shredding of chromosomes, known as chromothripsis, in 18% of high stage neuroblastoma6. These tumours are associated with a poor outcome. Structural alterations recurrently affected ODZ3, PTPRD and CSMD1, which are involved in neuronal growth cone stabilization7, 8, 9. In addition, ATRX, TIAM1 and a series of regulators of the Rac/Rho pathway were mutated, further implicating defects in neuritogenesis in neuroblastoma. Most tumours with defects in these genes were aggressive high stage neuroblastomas, but did not carry MYCN amplifications. The genomic landscape of neuroblastoma therefore reveals two novel molecular defects, chromothripsis and van cleef and arpels bracelets copy neuritogenesis gene alterations, which frequently occur in high risk tumours.
a, The number of amino acid changing mutations in 87 primary neuroblastoma (single nucleotide variants (SNVs) in red, deletions in grey, insertions in green and substitutions affecting more than 1 base pair (Sub) in blue). Numbers shown are events after CGAtools CallDiff with somatic scores and not present in dbSNP130, nor in 46 reference genomes released by Complete Genomics. b, Average number of mutations per tumour stage (International Neuroblastoma Staging System (INSS) stage 1, n = 9; stage 2, n = 14; stage 3, n = 5; stage 4, n = 50 and stage 4S, n = 9). Boxes include 50% of data and error bars indicate extremes with a maximum of two times the box size. st., stage. c, Kaplan curves for tumours with high versus low frequency of mutations. The optimal cut off level for the categories was determined by Kaplan scanning (see Supplementary Information and Methods). The significance (log rank test) was corrected for the multiple testing (Bonferroni correction). Number of patients per group is shown in parentheses. d, Age at diagnosis (rank order) versus the number of somatic variants. e, Average number of structural variations per tumour stage (INSS). Group sizes and the definition of the error bars as in Fig. 1b.
a, Circos plot showing structural variations in sample N492. The inner ring represents the copy number variations (red, gain; green, loss) based on coverage of the tumour and lymphocyte genomes. The lines traversing the ring indicate inter and intrachromosomal rearrangements identified by discordant mate pairs from paired end reads. N492 is a chromothripsis sample with an extreme amount of junctions on chromosome 5. b, Circos plot of the affected chromosome 5 in sample N492. c, Kaplan curves of the overall survival for tumours with or without chromothripsis. Numbers of patients per group are shown between brackets.
a, Coverage plots displaying the structural variations in the ATRX gene. The dots indicate summed coverage for bins of 1,000 pairs of the tumour genome, normalized to the coverage in corresponding normal tissue. The intron exon structure of ATRX is shown in red (dark red are exons). b, ATRX mRNA expression of 70 tumours as measured on Affymetrix full exon arrays. Tumours with ATRX deletions are encircled.
a, Diagram of a neurite growth cone depicting the function of the proteins encoded by genes with genomic aberrations in neuritogenesis. Red proteins have defects (for references see Supplementary Table 8). Rac and Rho small GTPases cycle between an inactive GDP bound and active GTP bound conformation, transducing signals from a wide variety of membrane receptors. They are activated by GEFs and inactivated by GAPs. Guanine nucleotide dissociation inhibitors (GDIs) sequester GDP bound GTPases. Proteins with aberrations in more than one tumour are marked with an asterisk (). b, Diagram of genetic defects and clinical parameters of all 87 sequenced neuroblastoma. Each vertical lane summarizes one tumour. Patients are sorted by the presence of genomic aberrations in neuritogenesis genes (Neuritogenesis, n = 19), by MYCN amplification (MYCN, n = 23), and by INSS stage (high to low). Middle panel, amino acid changing mutations and structural variations are indicated for all genes having two or more events and that are involved in neuritogenesis (red, mutated or structural variant; grey, not affected).
Neuroblastoma have a highly variable clinical outcome, with an excellent prognosis for stage 1 and 2 tumours, but a poor outcome for high stage tumours. Stage 4S neuroblastoma are metastasized but nevertheless undergo spontaneous regression. Low stage tumours are marked by numeric changes of chromosomal copy numbers, whereas high stage tumours typically show structural chromosomal defects resulting in, for example, hemizygous deletions of the chromosomal regions 1p36 or 11q and gain of 17q (refs 1, 10 Age at diagnosis above 1.5 is associated with high stage tumours and poor outcome.
We performed whole genome paired end sequencing as used by Complete Genomics13 for 87 untreated primary neuroblastoma tumours of all stages (Supplementary Table 1) and their corresponding lymphocyte DNAs. All samples had a minimal tumour content of 80% as determined by immunohistochemical analysis. Genomes were sequenced at an average coverage of 50 and an average fully called genome fraction of 96.6% (Supplementary Table 2). Compared to the HG18 reference genome we obtained an average of 3,347,592 single nucleotide variants (SNVs) per genome, in accordance with reported frequencies of interpersonal variants. Validation of 1,014 candidate somatic small mutations (SNVs, substitutions, insertions, deletions), including 763 SNVs, established a specificity of 88% and a sensitivity of 85% at a somatic score cut off of 0.1 (Supplementary Fig. 1a). SNVs above this score and all validated SNVs with lower scores were used for further analyses (total 586 genes, Supplementary Table 3). The sequence data identified an average of 12 somatic candidate amino acid affecting mutations per tumour (Fig. 1a and Supplementary Fig. 1b). 1b). 1d), as was also observed in medulloblastoma14. Within high stage neuroblastoma, MYCN amplification status did not correlate to mutation frequency (Supplementary Fig. 1c).
a, The number of amino acid changing mutations in 87 primary neuroblastoma (single nucleotide variants (SNVs) in red, deletions in grey, insertions in green and substitutions affecting more than 1 base pair (Sub) in blue). Numbers shown are events after CGAtools CallDiff with somatic scores and not present in dbSNP130, nor in 46 reference genomes released by Complete Genomics. b, Average number of mutations per tumour stage (International Neuroblastoma Staging System (INSS) stage 1, n = 9; stage 2, n = 14; stage 3, n = 5; stage 4, n = 50 and stage 4S, n = 9). Boxes include 50% of data and error bars indicate extremes with a maximum of two times the box size. st., stage. c, Kaplan curves for tumours with high versus low frequency of mutations. The optimal cut off level for the categories was determined by Kaplan scanning (see Supplementary Information and Methods). The significance (log rank test) was corrected for the multiple testing (Bonferroni correction). Number of patients per group is shown in parentheses. d, Age at diagnosis (rank order) versus the number of somatic variants. e, Average number of structural variations per tumour stage (INSS). Group sizes and the definition of the error bars as in Fig. 1b.
Only very few recurrent mutations were identified. ALK mutations were found in 6% of the tumours, in accordance with frequencies established in large neuroblastoma tumour series (Supplementary Table 4)2, 3, 4, 5. Three tumours carried mutations in TIAM1, a known regulator of cytoskeleton organization and neuritogenesis15. In a parallel study we sequenced four primary neuroblastoma tumours as well as cell lines derived from these tumours and their metastases. et al., submitted). Together with the lack of recurrent mutations, our data indicate that neuroblastoma carry few early somatic tumour driving mutations with amino acid changing consequences.
Analysis of the paired end clones with bracelet van cleef and arpels copy discordant ends can be used to identify candidate structural rearrangements, which together with sequence coverage data can identify somatic structural variants (SVs). Comparison of tumour versus lymphocyte coverage generated ultra high resolution comparative genomic hybridization (CGH) like profiles (Supplementary Fig. 2a). Analysis of the frequency of structural variations per chromosome revealed ten tumours with chromothripsis characteristics6 (see Methods). Chromothripsis is a localized shredding of a chromosomal region and subsequent random reassembly of the fragments. An extreme example of chromothripsis in chromosome 5 is shown in Fig. 2a and 2b (for other cases see Supplementary Fig. 2b). 2c). They were found in 18% of the stage 3 and 4 neuroblastoma, but not in low stage tumours (Fisher exact test P = 0.01). Accordingly, their prognostic impact is not independent of age and stage in multivariate analyses. Chromothripsis related structural aberrations frequently affected genes involved in neuroblastoma pathogenesis and were associated with amplification of MYCN or CDK4 and loss of heterozygosity of 1p (Supplementary Fig. 2c). In one tumour, chromothripsis resulted in amplification and very strong overexpression of MYC (c Myc) (Supplementary Fig. 2d). Chromosome 5 had undergone chromothripsis in three tumours, but no clear tumorigenic target on this chromosome was identified. To identify genetic defects that allowed chromothripsis and subsequent survival of the cell, we searched for defects in DNA damage response pathways in tumours with chromothripsis. The most extreme case of chromothripsis (N492, Fig. 2a and 2b) showed an inactivating deletion in FANCM and another chromothripsis tumour sample (N576) had a missense mutation in FAN1, predicted to be damaging by the polyphen2 program16. These findings might suggest involvement of inactivating events in the Fanconi anaemia signalling pathway to allow chromothripsis17.
a, Circos plot showing structural variations in sample N492. The inner ring represents the copy number variations (red, gain; green, loss) based on coverage of the tumour and lymphocyte genomes. The lines traversing the ring indicate inter and intrachromosomal rearrangements identified by discordant mate pairs from paired end reads. N492 is a chromothripsis sample with an extreme amount of junctions on chromosome 5. b, Circos plot of the van cleef arpels bracelet replica affected chromosome 5 in sample N492. c, Kaplan curves of the overall survival for tumours with or without chromothripsis. Numbers of patients per group are shown between brackets.
Full genome paired end sequencing allowed us to identify structural variants specifically perturbing single genes (see Methods and Supplementary Fig. 4 for selection procedure). We detected a total of 451 genes harbouring structural variants (306 genes without the events on chromothripsis chromosomes, Supplementary Tables 5 and 6). The structural variants often consisted of deletions of one or a few exons, inversions or translocations deleting part of a gene. One tumour showed an intrachromosomal rearrangement activating FOXR1 transcription (Supplementary Fig. 2e), which we recently identified as a recurrent but rare event in neuroblastoma18. Similar to the findings for amino acid changing mutations, there was a strong relation between the frequency of structural variations and the tumour stage (one way ANOVA P = 0.03; Fig. 1e), which extends the well established relationship between tumour stage and structural chromosomal defects in neuroblastoma10, 11, 12. Breakpoints identifying deletions were supported by changes in coverage plots. Most of the structural variants affected only one allele of a gene (Supplementary Table 5). This indicates that the tumour driving mechanism of these defects is haploinsufficiency, possibly combined with epigenetic attenuation of the non affected allele. On average, genes with structural variants resulting in loss of coverage indeed showed a reduced expression in tumours with these defects, as compared to tumours with normal alleles (Supplementary Fig. 2f). As an additional validation, we generated SNP arrays of 52 of the sequenced tumours. Although the SNP data have a much lower resolution than the sequence coverage plots, they supported the deletions and gains of sufficient size. This is especially evident on plots of chromothripsis samples (Supplementary Fig. 2g).
To identify relevant genes and pathways that contribute to neuroblastoma pathogenesis, we generated one list of all genes with amino acid changing mutations (n = 586), mutations in splice junctions (n = 37) and structural variations (n = 451). The total of 1,041 genes with alterations were analysed by two approaches. First, we analysed the most frequently affected genes (Supplementary Table 7). Four genes belonged to the MYCN amplicons (MYCN, MYCNOS, DDX1 and NBAS) and except for MYCN probably play no role in pathogenesis. Three genes, PTPRD, ODZ3 and ATRX, showed structural variants in five tumours each (Fig. 3a and Supplementary Fig. 3a) and 61 genes showed alterations in two to four tumours (Supplementary Table 7). This strongly indicates that at least the defects in PTPRD, ATRX and ODZ3 did not accumulate due to for example, the genomic length of the genes, but that they were selected for during the process of tumorigenesis.
a, Coverage plots displaying the structural variations in the ATRX gene. The dots indicate summed coverage for bins of 1,000 pairs of the tumour genome, normalized to the coverage in corresponding normal tissue. The intron exon structure of ATRX is shown in red (dark red are exons). b, ATRX mRNA expression of 70 tumours as measured on Affymetrix full exon arrays. Tumours with ATRX deletions are encircled.
The X chromosome encoded ATRX gene was affected by structural variants in five tumours (Fig. 3a). In two male patients this resulted in complete inactivation of the gene. Frequent ATRX defects were recently found in pancreatic neuroendocrine tumours19. ATRX is a chromatin remodelling protein involved in exchange of H3.3 in GC rich repeats and mutations of this gene are associated with X linked mental retardation20. Exon mRNA profiles of part of the sequenced series showed that the three samples included with ATRX structural variations had the lowest ATRX mRNA expression of all samples and showed a specific collapse of the signal in the deleted regions, illustrating the inactivating nature of the ATRX defects (Fig. 3b and Supplementary Fig. 3b).
ODZ3 and PTPRD were also hit by structural variations in five tumours each (Supplementary Fig. 3a). One tumour showed homozygous inactivation of ODZ3 (see legends of Supplementary Fig. 3a). In addition, ODZ2 and ODZ4, two highly homologous members of the conserved ODZ family, were together affected three times. PTPRD and ODZ genes encode transmembrane receptors expressed in the developing nervous system and localizing to axons and axonal growth cones21. Targeted silencing of ODZ homologues in Drosophila, Caenorhabditis elegans and mouse caused severe axon guidance defects9. Overexpression of ODZ2 in neuroblastoma cells enhanced neuritogenesis22. PTPRD is a member of the LAR subfamily of receptor protein tyrosine phosphatases. Transgenic mouse models strongly implicate the LAR subfamily receptors in neuritogenesis8. PTPRD defects in neuroblastoma were reported previously23. 3a). Interestingly, CSMD1, which showed structural variants in three tumours, is also a transmembrane protein expressed on nerve growth cones7. As the frequencies of PTPRD and ODZ3 defects exclude that they were found by chance, we propose that the function of these genes and of ODZ2, ODZ4 and CSMD1 in neuronal growth cones might hold a clue to their function in neuroblastoma pathogenesis.
The second analysis that we performed for the list for 1,041 affected genes was a gene ontology study to identify enrichment of genes with defects in specific molecular processes. This finding urged us to further investigate GTPase regulating genes in the list. TIAM1 was mutated in three tumours (see Supplementary Table 4). It functions as a guanine nucleotide exchange factor (GEF) for the small GTPase Rac and is, together with Rac, central to regulation of cellular polarity and neuritogenesis24, 25. The W1285S mutation creates a premature stop codon in the carboxy terminal pleckstrin homology domain required for Rac activation, whereas the other mutations were predicted to be damaging by polyphen2 analysis16. Rac is activated by GEFs and inactivated by GTPase activating proteins (GAPs)26 (Fig. 4). We identified a total of eight alterations in six GEFs specific for Rac (including TIAM1), but none in GAPs specific for Rac (Supplementary Tables 7, 8 and 10 for functional consequences). Whereas activation of Rac1 stimulates neuritogenesis, activation of its small GTPase antagonist RhoA promotes axon retraction and growth cone collapse (Fig. 4a)15. Strikingly, we detected seven alterations in five GAPs for RhoA, but only one GEF specific for RhoA (ARHGEF12) showed a translocation with unknown functional consequences (Fig. 4a, Supplementary Tables 7, 8 and 10 for functional consequences). Of note, transgenic mice with ATRX mutations causing mental retardation in humans showed abnormal dendritic spine formation with increased TIAM1 phosphorylation and Rac1 signalling27.
a, Diagram of a neurite growth cone depicting the function of the proteins encoded by genes with genomic aberrations in neuritogenesis. Red proteins have defects (for references see Supplementary Table 8). Rac and Rho small GTPases cycle between an inactive GDP bound and active GTP bound conformation, transducing signals from a wide variety of membrane receptors. They are activated by GEFs and inactivated by GAPs. Guanine nucleotide dissociation inhibitors (GDIs) sequester GDP bound GTPases. Proteins with aberrations in more than one tumour are marked with an asterisk (). b, Diagram of genetic defects and clinical parameters of all 87 sequenced neuroblastoma. Each vertical lane summarizes one tumour. Patients are sorted by the presence of genomic aberrations in neuritogenesis genes (Neuritogenesis, n = 19), by MYCN amplification (MYCN, n = 23), and by INSS stage (high to low). Middle panel, amino acid changing mutations and structural variations are indicated for all genes having two or more events and that are involved in neuritogenesis (red, mutated or structural variant; grey, not affected).
We conclude that alterations with significant frequencies (PTPRD and ODZ genes) affect transmembrane receptors that function in neuronal growth cone guidance and maintenance. In addition gene ontology analysis of the 1,041 genes showed significant enrichment of GTPase regulating genes. Alterations in GEFs for Rac and GAPs for Rho significantly deviate from a random distribution, implicating inhibition of Rac1 and activation of RhoA in impairing neuritogenesis in neuroblastoma (Fig. 4a).
From these findings we propose that defects in neuritogenesis regulating genes form an important category of tumour driving events in neuroblastoma. For a preliminary analysis of tumours with these defects, we selected the genes with recurrent defects in tumours that function in neuronal growth cones (PTPRD, ODZ3, ODZ2, CSMD1) or regulation of these processes through Rac/Rho signalling (TIAM1, DLC1, ARHGAP10, ATRX). The 19 tumours with defects in these genes were almost all stage 3 and 4 tumours diagnosed above 1.5
Neuroblastoma is a childhood tumour of the peripheral sympathetic nervous system. The pathogenesis has for a long time been quite enigmatic, as only very few gene defects were identified in this often lethal tumour1. Frequently detected gene alterations are limited to MYCN amplification (20%) and ALK activations (7%)2, 3, 4, 5. Here we present a whole genome sequence analysis of 87 neuroblastoma of all stages. Few recurrent amino acid changing mutations were found. In contrast, analysis of structural defects identified a local shredding of chromosomes, known as chromothripsis, in 18% of high stage neuroblastoma6. These tumours are associated with a poor outcome. Structural alterations recurrently affected ODZ3, PTPRD and CSMD1, which are involved in neuronal growth cone stabilization7, 8, 9. In addition, ATRX, TIAM1 and a series of regulators of the Rac/Rho pathway were mutated, further implicating defects in neuritogenesis in neuroblastoma. Most tumours with defects in these genes were aggressive high stage neuroblastomas, but did not carry MYCN amplifications. The genomic landscape of neuroblastoma therefore reveals two novel molecular defects, chromothripsis and van cleef and arpels bracelets copy neuritogenesis gene alterations, which frequently occur in high risk tumours.
a, The number of amino acid changing mutations in 87 primary neuroblastoma (single nucleotide variants (SNVs) in red, deletions in grey, insertions in green and substitutions affecting more than 1 base pair (Sub) in blue). Numbers shown are events after CGAtools CallDiff with somatic scores and not present in dbSNP130, nor in 46 reference genomes released by Complete Genomics. b, Average number of mutations per tumour stage (International Neuroblastoma Staging System (INSS) stage 1, n = 9; stage 2, n = 14; stage 3, n = 5; stage 4, n = 50 and stage 4S, n = 9). Boxes include 50% of data and error bars indicate extremes with a maximum of two times the box size. st., stage. c, Kaplan curves for tumours with high versus low frequency of mutations. The optimal cut off level for the categories was determined by Kaplan scanning (see Supplementary Information and Methods). The significance (log rank test) was corrected for the multiple testing (Bonferroni correction). Number of patients per group is shown in parentheses. d, Age at diagnosis (rank order) versus the number of somatic variants. e, Average number of structural variations per tumour stage (INSS). Group sizes and the definition of the error bars as in Fig. 1b.
a, Circos plot showing structural variations in sample N492. The inner ring represents the copy number variations (red, gain; green, loss) based on coverage of the tumour and lymphocyte genomes. The lines traversing the ring indicate inter and intrachromosomal rearrangements identified by discordant mate pairs from paired end reads. N492 is a chromothripsis sample with an extreme amount of junctions on chromosome 5. b, Circos plot of the affected chromosome 5 in sample N492. c, Kaplan curves of the overall survival for tumours with or without chromothripsis. Numbers of patients per group are shown between brackets.
a, Coverage plots displaying the structural variations in the ATRX gene. The dots indicate summed coverage for bins of 1,000 pairs of the tumour genome, normalized to the coverage in corresponding normal tissue. The intron exon structure of ATRX is shown in red (dark red are exons). b, ATRX mRNA expression of 70 tumours as measured on Affymetrix full exon arrays. Tumours with ATRX deletions are encircled.
a, Diagram of a neurite growth cone depicting the function of the proteins encoded by genes with genomic aberrations in neuritogenesis. Red proteins have defects (for references see Supplementary Table 8). Rac and Rho small GTPases cycle between an inactive GDP bound and active GTP bound conformation, transducing signals from a wide variety of membrane receptors. They are activated by GEFs and inactivated by GAPs. Guanine nucleotide dissociation inhibitors (GDIs) sequester GDP bound GTPases. Proteins with aberrations in more than one tumour are marked with an asterisk (). b, Diagram of genetic defects and clinical parameters of all 87 sequenced neuroblastoma. Each vertical lane summarizes one tumour. Patients are sorted by the presence of genomic aberrations in neuritogenesis genes (Neuritogenesis, n = 19), by MYCN amplification (MYCN, n = 23), and by INSS stage (high to low). Middle panel, amino acid changing mutations and structural variations are indicated for all genes having two or more events and that are involved in neuritogenesis (red, mutated or structural variant; grey, not affected).
Neuroblastoma have a highly variable clinical outcome, with an excellent prognosis for stage 1 and 2 tumours, but a poor outcome for high stage tumours. Stage 4S neuroblastoma are metastasized but nevertheless undergo spontaneous regression. Low stage tumours are marked by numeric changes of chromosomal copy numbers, whereas high stage tumours typically show structural chromosomal defects resulting in, for example, hemizygous deletions of the chromosomal regions 1p36 or 11q and gain of 17q (refs 1, 10 Age at diagnosis above 1.5 is associated with high stage tumours and poor outcome.
We performed whole genome paired end sequencing as used by Complete Genomics13 for 87 untreated primary neuroblastoma tumours of all stages (Supplementary Table 1) and their corresponding lymphocyte DNAs. All samples had a minimal tumour content of 80% as determined by immunohistochemical analysis. Genomes were sequenced at an average coverage of 50 and an average fully called genome fraction of 96.6% (Supplementary Table 2). Compared to the HG18 reference genome we obtained an average of 3,347,592 single nucleotide variants (SNVs) per genome, in accordance with reported frequencies of interpersonal variants. Validation of 1,014 candidate somatic small mutations (SNVs, substitutions, insertions, deletions), including 763 SNVs, established a specificity of 88% and a sensitivity of 85% at a somatic score cut off of 0.1 (Supplementary Fig. 1a). SNVs above this score and all validated SNVs with lower scores were used for further analyses (total 586 genes, Supplementary Table 3). The sequence data identified an average of 12 somatic candidate amino acid affecting mutations per tumour (Fig. 1a and Supplementary Fig. 1b). 1b). 1d), as was also observed in medulloblastoma14. Within high stage neuroblastoma, MYCN amplification status did not correlate to mutation frequency (Supplementary Fig. 1c).
a, The number of amino acid changing mutations in 87 primary neuroblastoma (single nucleotide variants (SNVs) in red, deletions in grey, insertions in green and substitutions affecting more than 1 base pair (Sub) in blue). Numbers shown are events after CGAtools CallDiff with somatic scores and not present in dbSNP130, nor in 46 reference genomes released by Complete Genomics. b, Average number of mutations per tumour stage (International Neuroblastoma Staging System (INSS) stage 1, n = 9; stage 2, n = 14; stage 3, n = 5; stage 4, n = 50 and stage 4S, n = 9). Boxes include 50% of data and error bars indicate extremes with a maximum of two times the box size. st., stage. c, Kaplan curves for tumours with high versus low frequency of mutations. The optimal cut off level for the categories was determined by Kaplan scanning (see Supplementary Information and Methods). The significance (log rank test) was corrected for the multiple testing (Bonferroni correction). Number of patients per group is shown in parentheses. d, Age at diagnosis (rank order) versus the number of somatic variants. e, Average number of structural variations per tumour stage (INSS). Group sizes and the definition of the error bars as in Fig. 1b.
Only very few recurrent mutations were identified. ALK mutations were found in 6% of the tumours, in accordance with frequencies established in large neuroblastoma tumour series (Supplementary Table 4)2, 3, 4, 5. Three tumours carried mutations in TIAM1, a known regulator of cytoskeleton organization and neuritogenesis15. In a parallel study we sequenced four primary neuroblastoma tumours as well as cell lines derived from these tumours and their metastases. et al., submitted). Together with the lack of recurrent mutations, our data indicate that neuroblastoma carry few early somatic tumour driving mutations with amino acid changing consequences.
Analysis of the paired end clones with bracelet van cleef and arpels copy discordant ends can be used to identify candidate structural rearrangements, which together with sequence coverage data can identify somatic structural variants (SVs). Comparison of tumour versus lymphocyte coverage generated ultra high resolution comparative genomic hybridization (CGH) like profiles (Supplementary Fig. 2a). Analysis of the frequency of structural variations per chromosome revealed ten tumours with chromothripsis characteristics6 (see Methods). Chromothripsis is a localized shredding of a chromosomal region and subsequent random reassembly of the fragments. An extreme example of chromothripsis in chromosome 5 is shown in Fig. 2a and 2b (for other cases see Supplementary Fig. 2b). 2c). They were found in 18% of the stage 3 and 4 neuroblastoma, but not in low stage tumours (Fisher exact test P = 0.01). Accordingly, their prognostic impact is not independent of age and stage in multivariate analyses. Chromothripsis related structural aberrations frequently affected genes involved in neuroblastoma pathogenesis and were associated with amplification of MYCN or CDK4 and loss of heterozygosity of 1p (Supplementary Fig. 2c). In one tumour, chromothripsis resulted in amplification and very strong overexpression of MYC (c Myc) (Supplementary Fig. 2d). Chromosome 5 had undergone chromothripsis in three tumours, but no clear tumorigenic target on this chromosome was identified. To identify genetic defects that allowed chromothripsis and subsequent survival of the cell, we searched for defects in DNA damage response pathways in tumours with chromothripsis. The most extreme case of chromothripsis (N492, Fig. 2a and 2b) showed an inactivating deletion in FANCM and another chromothripsis tumour sample (N576) had a missense mutation in FAN1, predicted to be damaging by the polyphen2 program16. These findings might suggest involvement of inactivating events in the Fanconi anaemia signalling pathway to allow chromothripsis17.
a, Circos plot showing structural variations in sample N492. The inner ring represents the copy number variations (red, gain; green, loss) based on coverage of the tumour and lymphocyte genomes. The lines traversing the ring indicate inter and intrachromosomal rearrangements identified by discordant mate pairs from paired end reads. N492 is a chromothripsis sample with an extreme amount of junctions on chromosome 5. b, Circos plot of the van cleef arpels bracelet replica affected chromosome 5 in sample N492. c, Kaplan curves of the overall survival for tumours with or without chromothripsis. Numbers of patients per group are shown between brackets.
Full genome paired end sequencing allowed us to identify structural variants specifically perturbing single genes (see Methods and Supplementary Fig. 4 for selection procedure). We detected a total of 451 genes harbouring structural variants (306 genes without the events on chromothripsis chromosomes, Supplementary Tables 5 and 6). The structural variants often consisted of deletions of one or a few exons, inversions or translocations deleting part of a gene. One tumour showed an intrachromosomal rearrangement activating FOXR1 transcription (Supplementary Fig. 2e), which we recently identified as a recurrent but rare event in neuroblastoma18. Similar to the findings for amino acid changing mutations, there was a strong relation between the frequency of structural variations and the tumour stage (one way ANOVA P = 0.03; Fig. 1e), which extends the well established relationship between tumour stage and structural chromosomal defects in neuroblastoma10, 11, 12. Breakpoints identifying deletions were supported by changes in coverage plots. Most of the structural variants affected only one allele of a gene (Supplementary Table 5). This indicates that the tumour driving mechanism of these defects is haploinsufficiency, possibly combined with epigenetic attenuation of the non affected allele. On average, genes with structural variants resulting in loss of coverage indeed showed a reduced expression in tumours with these defects, as compared to tumours with normal alleles (Supplementary Fig. 2f). As an additional validation, we generated SNP arrays of 52 of the sequenced tumours. Although the SNP data have a much lower resolution than the sequence coverage plots, they supported the deletions and gains of sufficient size. This is especially evident on plots of chromothripsis samples (Supplementary Fig. 2g).
To identify relevant genes and pathways that contribute to neuroblastoma pathogenesis, we generated one list of all genes with amino acid changing mutations (n = 586), mutations in splice junctions (n = 37) and structural variations (n = 451). The total of 1,041 genes with alterations were analysed by two approaches. First, we analysed the most frequently affected genes (Supplementary Table 7). Four genes belonged to the MYCN amplicons (MYCN, MYCNOS, DDX1 and NBAS) and except for MYCN probably play no role in pathogenesis. Three genes, PTPRD, ODZ3 and ATRX, showed structural variants in five tumours each (Fig. 3a and Supplementary Fig. 3a) and 61 genes showed alterations in two to four tumours (Supplementary Table 7). This strongly indicates that at least the defects in PTPRD, ATRX and ODZ3 did not accumulate due to for example, the genomic length of the genes, but that they were selected for during the process of tumorigenesis.
a, Coverage plots displaying the structural variations in the ATRX gene. The dots indicate summed coverage for bins of 1,000 pairs of the tumour genome, normalized to the coverage in corresponding normal tissue. The intron exon structure of ATRX is shown in red (dark red are exons). b, ATRX mRNA expression of 70 tumours as measured on Affymetrix full exon arrays. Tumours with ATRX deletions are encircled.
The X chromosome encoded ATRX gene was affected by structural variants in five tumours (Fig. 3a). In two male patients this resulted in complete inactivation of the gene. Frequent ATRX defects were recently found in pancreatic neuroendocrine tumours19. ATRX is a chromatin remodelling protein involved in exchange of H3.3 in GC rich repeats and mutations of this gene are associated with X linked mental retardation20. Exon mRNA profiles of part of the sequenced series showed that the three samples included with ATRX structural variations had the lowest ATRX mRNA expression of all samples and showed a specific collapse of the signal in the deleted regions, illustrating the inactivating nature of the ATRX defects (Fig. 3b and Supplementary Fig. 3b).
ODZ3 and PTPRD were also hit by structural variations in five tumours each (Supplementary Fig. 3a). One tumour showed homozygous inactivation of ODZ3 (see legends of Supplementary Fig. 3a). In addition, ODZ2 and ODZ4, two highly homologous members of the conserved ODZ family, were together affected three times. PTPRD and ODZ genes encode transmembrane receptors expressed in the developing nervous system and localizing to axons and axonal growth cones21. Targeted silencing of ODZ homologues in Drosophila, Caenorhabditis elegans and mouse caused severe axon guidance defects9. Overexpression of ODZ2 in neuroblastoma cells enhanced neuritogenesis22. PTPRD is a member of the LAR subfamily of receptor protein tyrosine phosphatases. Transgenic mouse models strongly implicate the LAR subfamily receptors in neuritogenesis8. PTPRD defects in neuroblastoma were reported previously23. 3a). Interestingly, CSMD1, which showed structural variants in three tumours, is also a transmembrane protein expressed on nerve growth cones7. As the frequencies of PTPRD and ODZ3 defects exclude that they were found by chance, we propose that the function of these genes and of ODZ2, ODZ4 and CSMD1 in neuronal growth cones might hold a clue to their function in neuroblastoma pathogenesis.
The second analysis that we performed for the list for 1,041 affected genes was a gene ontology study to identify enrichment of genes with defects in specific molecular processes. This finding urged us to further investigate GTPase regulating genes in the list. TIAM1 was mutated in three tumours (see Supplementary Table 4). It functions as a guanine nucleotide exchange factor (GEF) for the small GTPase Rac and is, together with Rac, central to regulation of cellular polarity and neuritogenesis24, 25. The W1285S mutation creates a premature stop codon in the carboxy terminal pleckstrin homology domain required for Rac activation, whereas the other mutations were predicted to be damaging by polyphen2 analysis16. Rac is activated by GEFs and inactivated by GTPase activating proteins (GAPs)26 (Fig. 4). We identified a total of eight alterations in six GEFs specific for Rac (including TIAM1), but none in GAPs specific for Rac (Supplementary Tables 7, 8 and 10 for functional consequences). Whereas activation of Rac1 stimulates neuritogenesis, activation of its small GTPase antagonist RhoA promotes axon retraction and growth cone collapse (Fig. 4a)15. Strikingly, we detected seven alterations in five GAPs for RhoA, but only one GEF specific for RhoA (ARHGEF12) showed a translocation with unknown functional consequences (Fig. 4a, Supplementary Tables 7, 8 and 10 for functional consequences). Of note, transgenic mice with ATRX mutations causing mental retardation in humans showed abnormal dendritic spine formation with increased TIAM1 phosphorylation and Rac1 signalling27.
a, Diagram of a neurite growth cone depicting the function of the proteins encoded by genes with genomic aberrations in neuritogenesis. Red proteins have defects (for references see Supplementary Table 8). Rac and Rho small GTPases cycle between an inactive GDP bound and active GTP bound conformation, transducing signals from a wide variety of membrane receptors. They are activated by GEFs and inactivated by GAPs. Guanine nucleotide dissociation inhibitors (GDIs) sequester GDP bound GTPases. Proteins with aberrations in more than one tumour are marked with an asterisk (). b, Diagram of genetic defects and clinical parameters of all 87 sequenced neuroblastoma. Each vertical lane summarizes one tumour. Patients are sorted by the presence of genomic aberrations in neuritogenesis genes (Neuritogenesis, n = 19), by MYCN amplification (MYCN, n = 23), and by INSS stage (high to low). Middle panel, amino acid changing mutations and structural variations are indicated for all genes having two or more events and that are involved in neuritogenesis (red, mutated or structural variant; grey, not affected).
We conclude that alterations with significant frequencies (PTPRD and ODZ genes) affect transmembrane receptors that function in neuronal growth cone guidance and maintenance. In addition gene ontology analysis of the 1,041 genes showed significant enrichment of GTPase regulating genes. Alterations in GEFs for Rac and GAPs for Rho significantly deviate from a random distribution, implicating inhibition of Rac1 and activation of RhoA in impairing neuritogenesis in neuroblastoma (Fig. 4a).
From these findings we propose that defects in neuritogenesis regulating genes form an important category of tumour driving events in neuroblastoma. For a preliminary analysis of tumours with these defects, we selected the genes with recurrent defects in tumours that function in neuronal growth cones (PTPRD, ODZ3, ODZ2, CSMD1) or regulation of these processes through Rac/Rho signalling (TIAM1, DLC1, ARHGAP10, ATRX). The 19 tumours with defects in these genes were almost all stage 3 and 4 tumours diagnosed above 1.5
Rich Life Style Reflects Swaggart Empire's Wealth
BATON ROUGE, La. In the late 1950s, Jimmy Swaggart was roaming around the back roads of Louisiana in a broken down Chevrolet, earning about $40 a week from his preaching and gospel singing.
He has come a long way since then.
The controversial evangelist now heads a tax exempt enterprise that ranks, by almost any measure, as one of the most successful of its kind. Jimmy Swaggart World Ministries and its Bible college boasted revenues of $150 million in 1987 more than $500,000 each working day.
And Swaggart's vast revenues, interviews and documents here reveal, finance more than his nonprofit ministry. Behind a veil of secrecy, Swaggart and his family have adopted a life style that, had it not been achieved in pursuing what he is fond of calling "the work of the Lord," Swaggart himself might include in some of his public condemnations of secularism and materialism.
His two story, high columned "parsonage," as it is called by ministry officials, sits behind a tall fence to assure privacy and is situated on 20 landscaped acres, including a swimming pool. The highly polished parquet living room floor is partly covered with an Oriental carpet, and off the master bedroom is a step up Jacuzzi with faucets in the shape of golden swans.
Swaggart and his wife, Frances, drive matching late model Lincoln Town Cars and fly to appearances around the country in a private Gulfstream jet aircraft that once was owned by the Rockefeller family. The Swaggarts have accepted gifts from loyal members of his video flock that include a diamond studded gold Rolex watch, fine clothes and a mink coat.
When asked about such a life style, Elizabeth Fuller of Chattanooga, Tenn., a board member of the ministry, told The Times: "After years of hardship and traveling in poor circumstances, if the Lord chooses to bless him in his latter days, I don't quarrel with that."
Swaggart's temporary suspension from preaching as of last month, a result of his self confessed "moral lapse" with a prostitute, may have a devastating effect on his ministry's income. But ministry officials have enough taped broadcasts to keep his weekly show on the air for months to come if local stations still want it.
Officials said Friday that because of a sudden drop off in contributions, more than 100 employees had been laid off and construction of new ministry buildings had been halted. The organization said it would hold a telethon in an effort to revive donations.
Seen on 200 Stations
Of Swaggart's $150 million in 1987 revenues, fully $135 million came from voluntary contributions generated both by his television ministry which appears on 200 stations in the United States and is copy van cleef and arpels necklace beamed to 145 countries in English and 15 foreign languages and by fund raising letters that are mailed at a rate of 7 million pieces a day.
The rest represented proceeds from the sales of gospel records and tapes, Bibles, books and T shirts by the largest mail order business in Louisiana and one of the biggest in the country.
Officials of Swaggart's ministry insist they can account for the spending of van cleef and arpel necklace fake every penny of the $150 million. Almost half, they say, paid television production costs, including the purchase of equipment, and bought air time for the broadcasts seen around the world. Other large shares were used to build schools and to run food programs for children overseas and to meet administrative expenses that include a payroll of 1,200 employees and teachers.
The rapid growth of Swaggart's ministry just six years ago, revenues were only $60 million has gone largely unnoticed because Swaggart, until his confessed indiscretion, has avoided national controversy and because his organization has maintained such financial secrecy.
Although nonprofit charitable organizations are exempt from taxation, most of them file with the Internal Revenue Service an annual information return that is open to public inspection. These returns, called Form 990s, show the amount of contributions received by the organization and for what purposes its funds were disbursed.
But according to imitation clover necklace van cleef IRS analyst Wilson Fadely, the Swaggart organization asked for and received official classification as a church in the late 1970s, and so it is not required to file any documents with any government agency, not even Form 990s. Congress, as part of the Internal Revenue Code, has long exempted churches from federal scrutiny.
Adding further to the ministry's financial secrecy is the fact that it is largely a family affair, with few outsiders in positions of influence.
The ministry's seven member executive board was effectively controlled for many years by four Swaggarts Jimmy, Frances, their only son, Donnie, and Donnie's wife, Debra. In recent months, however, the board has been expanded to 11 members with the addition of two more Assemblies of God preachers and two longtime Swaggart contributors.
BATON ROUGE, La. In the late 1950s, Jimmy Swaggart was roaming around the back roads of Louisiana in a broken down Chevrolet, earning about $40 a week from his preaching and gospel singing.
He has come a long way since then.
The controversial evangelist now heads a tax exempt enterprise that ranks, by almost any measure, as one of the most successful of its kind. Jimmy Swaggart World Ministries and its Bible college boasted revenues of $150 million in 1987 more than $500,000 each working day.
And Swaggart's vast revenues, interviews and documents here reveal, finance more than his nonprofit ministry. Behind a veil of secrecy, Swaggart and his family have adopted a life style that, had it not been achieved in pursuing what he is fond of calling "the work of the Lord," Swaggart himself might include in some of his public condemnations of secularism and materialism.
His two story, high columned "parsonage," as it is called by ministry officials, sits behind a tall fence to assure privacy and is situated on 20 landscaped acres, including a swimming pool. The highly polished parquet living room floor is partly covered with an Oriental carpet, and off the master bedroom is a step up Jacuzzi with faucets in the shape of golden swans.
Swaggart and his wife, Frances, drive matching late model Lincoln Town Cars and fly to appearances around the country in a private Gulfstream jet aircraft that once was owned by the Rockefeller family. The Swaggarts have accepted gifts from loyal members of his video flock that include a diamond studded gold Rolex watch, fine clothes and a mink coat.
When asked about such a life style, Elizabeth Fuller of Chattanooga, Tenn., a board member of the ministry, told The Times: "After years of hardship and traveling in poor circumstances, if the Lord chooses to bless him in his latter days, I don't quarrel with that."
Swaggart's temporary suspension from preaching as of last month, a result of his self confessed "moral lapse" with a prostitute, may have a devastating effect on his ministry's income. But ministry officials have enough taped broadcasts to keep his weekly show on the air for months to come if local stations still want it.
Officials said Friday that because of a sudden drop off in contributions, more than 100 employees had been laid off and construction of new ministry buildings had been halted. The organization said it would hold a telethon in an effort to revive donations.
Seen on 200 Stations
Of Swaggart's $150 million in 1987 revenues, fully $135 million came from voluntary contributions generated both by his television ministry which appears on 200 stations in the United States and is copy van cleef and arpels necklace beamed to 145 countries in English and 15 foreign languages and by fund raising letters that are mailed at a rate of 7 million pieces a day.
The rest represented proceeds from the sales of gospel records and tapes, Bibles, books and T shirts by the largest mail order business in Louisiana and one of the biggest in the country.
Officials of Swaggart's ministry insist they can account for the spending of van cleef and arpel necklace fake every penny of the $150 million. Almost half, they say, paid television production costs, including the purchase of equipment, and bought air time for the broadcasts seen around the world. Other large shares were used to build schools and to run food programs for children overseas and to meet administrative expenses that include a payroll of 1,200 employees and teachers.
The rapid growth of Swaggart's ministry just six years ago, revenues were only $60 million has gone largely unnoticed because Swaggart, until his confessed indiscretion, has avoided national controversy and because his organization has maintained such financial secrecy.
Although nonprofit charitable organizations are exempt from taxation, most of them file with the Internal Revenue Service an annual information return that is open to public inspection. These returns, called Form 990s, show the amount of contributions received by the organization and for what purposes its funds were disbursed.
But according to imitation clover necklace van cleef IRS analyst Wilson Fadely, the Swaggart organization asked for and received official classification as a church in the late 1970s, and so it is not required to file any documents with any government agency, not even Form 990s. Congress, as part of the Internal Revenue Code, has long exempted churches from federal scrutiny.
Adding further to the ministry's financial secrecy is the fact that it is largely a family affair, with few outsiders in positions of influence.
The ministry's seven member executive board was effectively controlled for many years by four Swaggarts Jimmy, Frances, their only son, Donnie, and Donnie's wife, Debra. In recent months, however, the board has been expanded to 11 members with the addition of two more Assemblies of God preachers and two longtime Swaggart contributors.
Striking Galaxy Images
Heart of the Milky Way CompositeMass of the entire Milky Way: estimates range from about 200 billion to 1.9 trillion solar masses. Karachentsev's "Catalog of nearby galaxies" gives 141 billion solar masses.
Diameter of the entire Milky Way: 100,000 light years.
An image from the Spitzer Space Telescope in infrared (IR) was combined with another from the Hubble in near infrared, and a third image from the Chandra X ray Observatory.
The image at right shows the three separate images.
Top: reddish clouds from Spitzer (IR).
Middle: golden streaks from Hubble (near IR).
Bottom: blue and violet clouds from Chandra (X ray). The LMC is one of the satellite galaxies of the Milky Way, visible only from the Southern Hemisphere or from near the equator. This is the largest satellite of our galaxy.
Distance: 157,000 replica van cleef and arpels necklace alhambra light years.
Mass: Estimates vary greatly and include 8.7 billion solar masses (van der Marel) and 3.3 billion solar masses (Karachentsev).
Near the LMC resides the Small Magellanic Cloud (SMC). This view includes its own stellar nursery. The SMC also orbits the Milky Way galaxy. The irregular shape of this galaxy is thought to have been caused by tidal interaction with both the LMC and the Milky Way. Three astrophysicists (Mathewson, Ford and Visvanathan) have proposed that copy van cleef arpels alhambra necklace there is a third Magellanic cloud behind the SMC, which they call the Mini clover necklace van cleef replica Magellanic Cloud (MMC), because they estimate that the SMC had been split in two many millions of years ago by the tidal forces from its larger neighbors.
Heart of the Milky Way CompositeMass of the entire Milky Way: estimates range from about 200 billion to 1.9 trillion solar masses. Karachentsev's "Catalog of nearby galaxies" gives 141 billion solar masses.
Diameter of the entire Milky Way: 100,000 light years.
An image from the Spitzer Space Telescope in infrared (IR) was combined with another from the Hubble in near infrared, and a third image from the Chandra X ray Observatory.
The image at right shows the three separate images.
Top: reddish clouds from Spitzer (IR).
Middle: golden streaks from Hubble (near IR).
Bottom: blue and violet clouds from Chandra (X ray). The LMC is one of the satellite galaxies of the Milky Way, visible only from the Southern Hemisphere or from near the equator. This is the largest satellite of our galaxy.
Distance: 157,000 replica van cleef and arpels necklace alhambra light years.
Mass: Estimates vary greatly and include 8.7 billion solar masses (van der Marel) and 3.3 billion solar masses (Karachentsev).
Near the LMC resides the Small Magellanic Cloud (SMC). This view includes its own stellar nursery. The SMC also orbits the Milky Way galaxy. The irregular shape of this galaxy is thought to have been caused by tidal interaction with both the LMC and the Milky Way. Three astrophysicists (Mathewson, Ford and Visvanathan) have proposed that copy van cleef arpels alhambra necklace there is a third Magellanic cloud behind the SMC, which they call the Mini clover necklace van cleef replica Magellanic Cloud (MMC), because they estimate that the SMC had been split in two many millions of years ago by the tidal forces from its larger neighbors.
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Van Gogh's paintings turning brown
Ella Hendriks of the Van Gogh Museum Amsterdam said: 'This type of cutting edge research is crucial to advance our understanding of how paintings age and should be conserved for future generations.'
Van Gogh's use of vibrant colours to convey mood and emotion was a milestone in the history of art and influenced generations of painters.
The new study looked at one of the 'new' paints chrome yellow which first appeared in the early 1800s. The warm orange yellow paint was made of toxic lead chromate and like many of the pigments of the period was chemically unstable.
Even in the 19th century, painters knew copy cuff bracelets for women that it turned to brown or faded over time. However, art restorers have long puzzled over why not all paintings using chrome yellow fade and why some darken faster than others.
The team of international scientists collected samples from three historic, half used tubes of paint.
After the samples were artificially aged for 500 hours under an ultraviolet lamp, only one sample from a paint tube belonging to the Flemish artist Rik Wouters, darkened to a chocolate brown.
The scientists used the same methods to study samples from two van Gogh paintings his 1888 View of Arles with Irises, and his 1887 Bank of the Seine Knockoff hermes leather bags from the Van Gogh Museum, Amsterdam.
The sample was analysed using an array of analytical tools, including the synchrotron X ray equipment at the European Synchrotron Radiation Facility (ESRF) in Grenoble, France.
The different contrast in the yellow colours used by the artist can be seen in Wheat Fields With Reaper, which was exhibited at the Royal Academy of Arts in Central London last year
Using the synchrotron's microscopic beam of X rays one hundred times thinner than the width of human hair, they found that a chemical reaction called oxidation reduction was altering the chromium atoms in the paint.
The reaction which leads to chromium atoms gaining extra electrons is triggered by sunlight and UV light penetrating the surface of the paint.
The change was most common in the presence of sulphur and barium ingredients added to lead white paint in the 19th century. The scientists believe van Gogh's technique of blending white and yellow paint may have caused the fading.
Dr Koen Janssens from Antwerp University, who published the findings in the journal Analytical Chemistry, said: 'Our next experiments are already in the pipeline. Obviously, we want to understand which conditions favour the reduction of chromium, and whether there is any hope to revert pigments to the original state in paintings where it is already taking place.'
Dr Marine Cotte, an ESRF scientist also working at copy white enamel jewelry La Muse du Louvre, said: 'Our X ray beam is one hundred times thinner than a human hair, fake enamel on gold jewelry and it reveals subtle chemical processes over equally minuscule areas.
'Making this possible has opened the door to a whole new world of discovery for art historians and conservators.'
Most watched News videos EXCLUSIVE: Ariana Grande plane arrives back in the US Moment armed police storm of Manchester suicide bomber Blood seen dripping from victim leg after Manchester Moment bomb explodes at Ariana Grande concert Homeless man describes how he helped after Manchester attack Terrifying scenes inside Manchester Arena as crowd flee concert Sickening video warns of more attacks after Manchester Girls scream and climb over barriers as they evacuate Manchester Arena Ariana Grande fans running away from venue after an explosion Forensic officers raid of Manchester suicide bomber no problems here Manchester Arena announcement urges no panic Eye witness describes spotting the Manchester attacker
EXCLUSIVE: First photos of Ariana Grande since Manchester. The schoolgirls massacred by ISIS coward: Five teenagers. Help for the homeless heroes: Millionaire West Ham owner. Father of Manchester Arena bomber Salman Abedi claims his. Theresa May warns a fresh terror attack is feared to be. 'Like bits of fire': Mother and daughter share photos of. EXCLUSIVE: Ariana Grande's hero mom who helped bring. Britain on lockdown: Army deploys 1,000 heavily armed. 'Our little princess has been so lucky': Father's joy as. Mother of teen, 18, killed in Manchester terror attack. Tourists watch in horror as armed police arrest man. Horror on the M6: Lorry driver is arrested after four. More than 24 hours on, desperate families still search. Aaron Hernandez's hell behind bars: NFL star killed. She STILL doesn't wanna hold his hand: Melania leaves. Terrorist's brother arrested: Dramatic moment armed. 'I won't forget what you said!' Trump tells Pope after. BREAKING NEWS: My son is innocent, insists father of. MOST READ NEWS Previous.
Ella Hendriks of the Van Gogh Museum Amsterdam said: 'This type of cutting edge research is crucial to advance our understanding of how paintings age and should be conserved for future generations.'
Van Gogh's use of vibrant colours to convey mood and emotion was a milestone in the history of art and influenced generations of painters.
The new study looked at one of the 'new' paints chrome yellow which first appeared in the early 1800s. The warm orange yellow paint was made of toxic lead chromate and like many of the pigments of the period was chemically unstable.
Even in the 19th century, painters knew copy cuff bracelets for women that it turned to brown or faded over time. However, art restorers have long puzzled over why not all paintings using chrome yellow fade and why some darken faster than others.
The team of international scientists collected samples from three historic, half used tubes of paint.
After the samples were artificially aged for 500 hours under an ultraviolet lamp, only one sample from a paint tube belonging to the Flemish artist Rik Wouters, darkened to a chocolate brown.
The scientists used the same methods to study samples from two van Gogh paintings his 1888 View of Arles with Irises, and his 1887 Bank of the Seine Knockoff hermes leather bags from the Van Gogh Museum, Amsterdam.
The sample was analysed using an array of analytical tools, including the synchrotron X ray equipment at the European Synchrotron Radiation Facility (ESRF) in Grenoble, France.
The different contrast in the yellow colours used by the artist can be seen in Wheat Fields With Reaper, which was exhibited at the Royal Academy of Arts in Central London last year
Using the synchrotron's microscopic beam of X rays one hundred times thinner than the width of human hair, they found that a chemical reaction called oxidation reduction was altering the chromium atoms in the paint.
The reaction which leads to chromium atoms gaining extra electrons is triggered by sunlight and UV light penetrating the surface of the paint.
The change was most common in the presence of sulphur and barium ingredients added to lead white paint in the 19th century. The scientists believe van Gogh's technique of blending white and yellow paint may have caused the fading.
Dr Koen Janssens from Antwerp University, who published the findings in the journal Analytical Chemistry, said: 'Our next experiments are already in the pipeline. Obviously, we want to understand which conditions favour the reduction of chromium, and whether there is any hope to revert pigments to the original state in paintings where it is already taking place.'
Dr Marine Cotte, an ESRF scientist also working at copy white enamel jewelry La Muse du Louvre, said: 'Our X ray beam is one hundred times thinner than a human hair, fake enamel on gold jewelry and it reveals subtle chemical processes over equally minuscule areas.
'Making this possible has opened the door to a whole new world of discovery for art historians and conservators.'
Most watched News videos EXCLUSIVE: Ariana Grande plane arrives back in the US Moment armed police storm of Manchester suicide bomber Blood seen dripping from victim leg after Manchester Moment bomb explodes at Ariana Grande concert Homeless man describes how he helped after Manchester attack Terrifying scenes inside Manchester Arena as crowd flee concert Sickening video warns of more attacks after Manchester Girls scream and climb over barriers as they evacuate Manchester Arena Ariana Grande fans running away from venue after an explosion Forensic officers raid of Manchester suicide bomber no problems here Manchester Arena announcement urges no panic Eye witness describes spotting the Manchester attacker
EXCLUSIVE: First photos of Ariana Grande since Manchester. The schoolgirls massacred by ISIS coward: Five teenagers. Help for the homeless heroes: Millionaire West Ham owner. Father of Manchester Arena bomber Salman Abedi claims his. Theresa May warns a fresh terror attack is feared to be. 'Like bits of fire': Mother and daughter share photos of. EXCLUSIVE: Ariana Grande's hero mom who helped bring. Britain on lockdown: Army deploys 1,000 heavily armed. 'Our little princess has been so lucky': Father's joy as. Mother of teen, 18, killed in Manchester terror attack. Tourists watch in horror as armed police arrest man. Horror on the M6: Lorry driver is arrested after four. More than 24 hours on, desperate families still search. Aaron Hernandez's hell behind bars: NFL star killed. She STILL doesn't wanna hold his hand: Melania leaves. Terrorist's brother arrested: Dramatic moment armed. 'I won't forget what you said!' Trump tells Pope after. BREAKING NEWS: My son is innocent, insists father of. MOST READ NEWS Previous.
Vancouver's hot rental market a challenge for students
VANCOUVER Madeleine Davis expects she could be couch surfing with friends when she heads back to university this fall. philosophy student and her two roommates, who have been searching since Aug. 1 for an affordable house close to the UBC campus.
"We're definitely running out of time," Davis, 22, said Tuesday. "We've had a lot of near misses but a lot of trouble finding somewhere. We're still looking and following up leads but it's quite a difficult time right now because everybody's looking."
Davis and her friends, who returned home after separate overseas experiences and internships this summer, never expected it would be so hard to find new digs.
But they're also in new territory: the copy cuff bracelets for women trio wants to live close to the university where rents tend to be higher than average at between $550 and $750 per room and they're facing increased competition from graduates, young families and many of the other 300,000 plus post secondary students vying for the same space in an ever tightening rental market.
Vacancy rates in Metro Vancouver edged downward in 2013, dropping to 1.7 per cent from 1.8 per cent in 2012, making it one of the lowest vacancy rates among the 27 centres surveyed in the province, according to Canada Mortgage and Housing Corp.'s latest Rental Market Report, released last fall.
Two bedroom apartments saw the biggest drop in vacancy rates, while rents rose marginally for one and three bedroom units across the region to an average of $1,005 per month.
A one bedroom in the City of Vancouver, for instance, went for an average of $1,090, compared with $1,198 in the West End and downtown, $953 in Richmond, $1,005 in North Vancouver, $900 in Burnaby and $751 in Surrey.
The University Endowment Lands had the highest rents for one bedroom units at an average $1,347 per month, followed by West Vancouver at $1,281 per month.
But for many students, even those average rents are way out of their league, and the suites may not even be suitable.
"It just gets really stressful, that you're going to be settling for something or paying more than you wanted to," said Raven Nyman, a third year UBC student who just signed a lease. "There were a lot of places we saw that were not the best."
Richard Sam, principal of surveys for CMHC, said the lower vacancy rate in Metro Vancouver is a Knockoff hermes leather bags simple tale of supply and demand, scripted by improving employment trends among the younger population who tend to rent, as well as a boost in international non resident migration.
Most new migrants tend to stay in and around the downtown city core when they first arrive, driving up the demand for rental housing. The University Endowment Lands and city of Vancouver had the lowest vacancy rates, for instance, while Surrey, Maple Ridge and Pitt Meadows had the most rental room to spare.
"We're just seeing more of an influx of students, to be honest," Sam said. "It's more of a supply and demand issue so we're seeing more students looking for placements around the universities. I would think the same thing is happening around Simon Fraser University in Burnaby."
He noted two bedroom units Knockoff orange hermes bag are seeing the lower vacancies as students seek to double up and share the rent in this hot button market.
John Calveley, of Alma Mater Society at UBC, said there has been a rising trend of students seeking two and three bedroom units off campus in the past few years as rents rose by five to 10 per cent.
While first year students can stay on campus, there's a wait list at both UBC and SFU, which means more people are looking for places outside.
Davis, who spent last Knockoff hermes orange bag year living near Commercial Drive in a five bedroom house for $2,500 per month, acknowledges it would be cheaper to live further away from the university but she doesn't want to face a hour long bus commute.
"It makes sense for us as students to live close to UBC," she said.
Nyman agrees. She has been living with family in North Vancouver this summer but wanted to find something in Dunbar, Kitsilano or Kerrisdale to avoid the cross town commute. She finally struck it lucky last weekend when she and two friends snagged a basement suite at Camosun and 41st Avenue.
Not only is it in a great location it's at the last bus stop before campus but is less than $500 per month for each of the girls, who had been prepared to pay at least $100 more than that.
"I don't know how we found it," said Nyman, 19. "I'm so happy."
Like Davis, Nyman was worried she wasn't going to find a suitable home in time. Although she started scouring the housing ads in April, there was nothing for students listed on Craigslist or Kijiji until August, which meant there was a run on the available spots.
In the past few weeks, Nyman and her friends viewed nearly 10 places, finding some that didn't even have promised amenities like a stove or washer and dryer.
In some cases, they arrived at an open house to find someone else signing a lease. And even when they found their dream suite on Camosun, it wasn't a given that they would get it, with at least 50 others wanting the space.
"You have to go a little out of your comfort zone because you have to be aggressive and persistent," Nyman said. "I really had to continue to text and call (the landlord). I had to be persistent to stay on his radar because there were so many good applicants. We had to stick out so we could snag the place."
Davis agreed that students have to be persuasive to get a spot, especially when they're up against families or experienced workers who have references to back up their applications.
"We're looking for anything. We haven't actually been that picky," she said. "The biggest problem we have is to try to convince people they should take a chance on us."
VANCOUVER Madeleine Davis expects she could be couch surfing with friends when she heads back to university this fall. philosophy student and her two roommates, who have been searching since Aug. 1 for an affordable house close to the UBC campus.
"We're definitely running out of time," Davis, 22, said Tuesday. "We've had a lot of near misses but a lot of trouble finding somewhere. We're still looking and following up leads but it's quite a difficult time right now because everybody's looking."
Davis and her friends, who returned home after separate overseas experiences and internships this summer, never expected it would be so hard to find new digs.
But they're also in new territory: the copy cuff bracelets for women trio wants to live close to the university where rents tend to be higher than average at between $550 and $750 per room and they're facing increased competition from graduates, young families and many of the other 300,000 plus post secondary students vying for the same space in an ever tightening rental market.
Vacancy rates in Metro Vancouver edged downward in 2013, dropping to 1.7 per cent from 1.8 per cent in 2012, making it one of the lowest vacancy rates among the 27 centres surveyed in the province, according to Canada Mortgage and Housing Corp.'s latest Rental Market Report, released last fall.
Two bedroom apartments saw the biggest drop in vacancy rates, while rents rose marginally for one and three bedroom units across the region to an average of $1,005 per month.
A one bedroom in the City of Vancouver, for instance, went for an average of $1,090, compared with $1,198 in the West End and downtown, $953 in Richmond, $1,005 in North Vancouver, $900 in Burnaby and $751 in Surrey.
The University Endowment Lands had the highest rents for one bedroom units at an average $1,347 per month, followed by West Vancouver at $1,281 per month.
But for many students, even those average rents are way out of their league, and the suites may not even be suitable.
"It just gets really stressful, that you're going to be settling for something or paying more than you wanted to," said Raven Nyman, a third year UBC student who just signed a lease. "There were a lot of places we saw that were not the best."
Richard Sam, principal of surveys for CMHC, said the lower vacancy rate in Metro Vancouver is a Knockoff hermes leather bags simple tale of supply and demand, scripted by improving employment trends among the younger population who tend to rent, as well as a boost in international non resident migration.
Most new migrants tend to stay in and around the downtown city core when they first arrive, driving up the demand for rental housing. The University Endowment Lands and city of Vancouver had the lowest vacancy rates, for instance, while Surrey, Maple Ridge and Pitt Meadows had the most rental room to spare.
"We're just seeing more of an influx of students, to be honest," Sam said. "It's more of a supply and demand issue so we're seeing more students looking for placements around the universities. I would think the same thing is happening around Simon Fraser University in Burnaby."
He noted two bedroom units Knockoff orange hermes bag are seeing the lower vacancies as students seek to double up and share the rent in this hot button market.
John Calveley, of Alma Mater Society at UBC, said there has been a rising trend of students seeking two and three bedroom units off campus in the past few years as rents rose by five to 10 per cent.
While first year students can stay on campus, there's a wait list at both UBC and SFU, which means more people are looking for places outside.
Davis, who spent last Knockoff hermes orange bag year living near Commercial Drive in a five bedroom house for $2,500 per month, acknowledges it would be cheaper to live further away from the university but she doesn't want to face a hour long bus commute.
"It makes sense for us as students to live close to UBC," she said.
Nyman agrees. She has been living with family in North Vancouver this summer but wanted to find something in Dunbar, Kitsilano or Kerrisdale to avoid the cross town commute. She finally struck it lucky last weekend when she and two friends snagged a basement suite at Camosun and 41st Avenue.
Not only is it in a great location it's at the last bus stop before campus but is less than $500 per month for each of the girls, who had been prepared to pay at least $100 more than that.
"I don't know how we found it," said Nyman, 19. "I'm so happy."
Like Davis, Nyman was worried she wasn't going to find a suitable home in time. Although she started scouring the housing ads in April, there was nothing for students listed on Craigslist or Kijiji until August, which meant there was a run on the available spots.
In the past few weeks, Nyman and her friends viewed nearly 10 places, finding some that didn't even have promised amenities like a stove or washer and dryer.
In some cases, they arrived at an open house to find someone else signing a lease. And even when they found their dream suite on Camosun, it wasn't a given that they would get it, with at least 50 others wanting the space.
"You have to go a little out of your comfort zone because you have to be aggressive and persistent," Nyman said. "I really had to continue to text and call (the landlord). I had to be persistent to stay on his radar because there were so many good applicants. We had to stick out so we could snag the place."
Davis agreed that students have to be persuasive to get a spot, especially when they're up against families or experienced workers who have references to back up their applications.
"We're looking for anything. We haven't actually been that picky," she said. "The biggest problem we have is to try to convince people they should take a chance on us."
the Godfather of Punk and Seamus Heaney Have in Common
There is a theory of "primitive affluence" that suggests that when a society has its primary needs met by Nature food, shelter, clothing then it will turn to creativity. Bali, a tropical island in Indonesia where the rich volcanic soil produces an abundance of food and materials for fabrics and building, is held as an example. The trope is that "everyone in Bali is an artist." Yet, while it is true that most everyone spends days carving, painting and dancing, there is very little originality in the products all are variations on a standard theme, precisely ritualistic, all expressed within rigid boundaries. The island's most famous dance, Kecak, was created by a German painter and musician, in the 1930s, intended as a performance for tourists.
On the other side of the field, Malcolm Gladwell, the counter intuitive craftsman, in his book David and Goliath: Underdogs, Misfits, and the Art of Battling Giants, promotes the idea of "desirable difficulty," wherein disadvantages propel people to extraordinary achievement and creativity.
Northern Ireland may be the poster child for Mr. Gladwell's theory. About the size of Connecticut, with less than half the population (about 2 million people), it has a wildly disproportionate number of fearless creatives and original thinkers. Yes, it is as far from "primitive affluence" as can be found. The land has few natural resources. Everything from coal to timber to iron has to be imported. For much of the year, the weather is cold and dank. And, for years, the region endured ethno nationalist and sectarian strife. One rumor has it that when archeologists broke into King Tut's tomb they found a newspaper with the headline, "Irish Problems Still Unsolved."
The exceedingly carbonated era that began in 1969, known as The Troubles, ended with the Good Friday Agreement of April 10, 1998, an accord that brought the Peace Dividend, a surge in cathexis with the land, and the beginnings of a surprising renaissance.
Yet, throughout its fractious history Northern Ireland has continued to unleash unreasonable creativity. The Kelvin scale was invented by a Belfastian; the ejection seat, portable defibrillator, modern tractor, the safety lamp for miners and chocolate milk by engineers from County Down. It could be argued distilled whiskey was concocted here, as the flush toilet.
On the entrepreneurial side, Northern Ireland, despite its challenges, became the largest linen producer in the world. And had the largest ropeworks. It was the largest manufacturer of fizzy drinks; largest shirt maker; had the largest flax machine works; largest tobacco factory; largest handkerchief factory in the world. For a time, a century ago, it was the world's leading industrial city, anchored by the biggest shipyard in the world, and there it created the biggest man made moving object in history: the ocean liner Titanic.
And then the arts. Lewis, Jack Higgins (who was raised here), Oscar Wilde (who schooled in County Fermanagh), Sir Kenneth Branagh, Patrick Magee, Sam Neill, Liam Neeson, and the most famous film star of the land, The DeLorean. There is not so much sun in this northern clip of the world, so folks are often inside sipping the hot cup of creativity, fanning the flames of magic turf.
When I read, then, that one of my teenage heroes, Van Morrison, was being awarded "The Freeman of Belfast" honor (which allows him to drive his herd of sheep through the center of town), I knew I had to go and jump into this place.
So well I remember standing on the sidelines at a high school mixer, too shy to cross the room and make the ask. But when Gloria, performed by Them (named for the 1954 horror movie about giant radioactive ants) with the deep burr of Van Morrison's voice slashing through paper walls, came on the record player, I found a beat and a gift of confidence I never knew I had, and strutted across the floor and asked the most beautiful girl to dance. And she said, "yes."
I won't commit the crime of clich and say his songs were the soundtrack of my life, but there were milestones marked in the Druidic forest trails of his music. "Moondance," for instance, enabled my own passage to freemanhood, and I'm sure I am not alone in that refrain.
With the first bite of fall I make the pilgrimage to Northern Ireland, to Belfast, where Van Morrison, after a life time of travel, and living in the artistic meccas of Woodstock and Marin County, has come home, to the place he was born.
I make my way to Waterfront Hall, and settle in just below Violet Morrison, Van's mom, in the balcony. It's a family affair, as the chief back up singer is Van's daughter, Shana.
Silence, anticipation seem in command. Then The Lord Mayor Mirtn Muilleoir takes the mic, and says, "He united us in the past, he's united us tonight and he will unite us in the future. This honor represents our love, respect and gratitude for Van Morrison from the 'dark side of the street to the bright side of the road'."
And Van the Freeman, six time Grammy winner, sporting signature dark suit, black hat and sunglasses, struts out stage left and gives a thumbs up to the crowd. He signs a special scroll, accepts a gold key to the city, bows, and then, without a word, picks up his alto sax, and launches into a sensual Celtic Swing.
And from there into "Moondance," "Brown Eyed Girl," and a roll call of greats, many citing patches of his personal map, sign posts and street names from his East Belfast boyhood. Van, of course, remains rock's foremost curmudgeon, and true to form he lets the music do the talking, rarely speaking, sometimes turning his back to the audience to play.
But at 68, after 50 years as a fiercely prolific copy van cleef pendant artist, he still summons the nerve to sing about the world as if it remains to be made, or as if it could be unmade, something he's witnessed in his hometown. As so many in Northern Ireland, he rattles the door of convention in its frame. And as he growls his lines, making himself into a sea monster, his daughter Shana swoops over him and digs van cleef bracelet replica into the songs, adding fervor in a glittering dress.
Just before Into the Mystic, The Belfast Cowboy sits down and jests: "This is the part where I hide behind the piano." A German journalist next to me, who has been to a score of Van's concerts, turns to me shocked and says "that's the most he's ever said at a concert." Then the piano takes off, like a boat untied, into waves of melody. There is the feeling that Van is looking back at his dock from a future already passed.
This is a "hand of history" moment in Belfast. We're immersed in something called "yarragh," fleeting elusive moments of transcendence, when the sense of an unrepeatable event is present. Like the city itself, this is an irresolvable adventure, someplace between the breaks and holes in the music.
He ends the municipal tribute with a muscle and fiber rendition of "Gloria," and I am transported back, as no doubt many in the audience, to teendom, to that moment when we loosed ourselves from words and floated on the bowers of his music.
Van is now a Freeman of Belfast, which is doubly significant, as just a few years ago men were not free to walk this city, and now they are.
The day after the concert I head out to meet another cyclone in residence, Terri Hooley, the "godfather of punk," at the latest awakening of his record shop, Good Vibrations, with its 1955 Elvis effigy out front. He is still, after all these years, hawking vinyl, posters, and the trending whiffs of the '70s. He insists we head over to the pub for a pint of Guinness with a brandy chaser, his preferred poison for the last half century. He lost an eye with a stray arrow as a boy, and has a reputation for plucking out his glass eye and dropping it into a drink, so I keep my pint out of reach. After a sip or few he shares, "I honestly believe punk bands saved countless lives, keeping impressionable young people away from the paramilitaries and giving us all something exciting to focus on."
Terri Hooley first opened his record shop on Great Victoria Street in 1976, at the time the most bombed piece of real estate in the world. It quickly became a safe haven, a neutral harbor, at a time when things were very thin on the ground. Teens and lost tribes from all sections and classes, from both sides of the divide, joined by a love of music, hung out in peace, preferring tunes to stones, music and culture more than the dead hand of sectarianism. It was a firefly of light in the blackness of Belfast at the time.
Though a Hank Williams fan in a polo neck, when he heard Punk it screeched his being. "To be a punk was to be different from the past." He started his own label, and produced edgy, alternative records. "Teenage Kicks," by the Undertones, was his biggest hit. He took the record to London and pedaled it around, but no one bit. "They said it was the worst record they ever heard in their lives." Then John Peel, the rock star DJ, played it on the BBC, twice, in a row, and the Undertones were signed to a major label. Hooley never did it for the money his store has gone bankrupt more times than the airlines and he still doesn't have any savings, but his unending efforts to build peace through music are recognized now around the world. "My brother was addicted to heroin; I'm addicted to having a record shop."
"For such a small population we have more talent per head of poets, painters and performers than anywhere else in Europe. Because of our in between status the arts give young people something to be proud of. It proves to every kid here that he can achieve something, and have a bloody good laugh doing it." Terri Hooley
Terri has a sign in his store at the top of the stairs, "Help the Aged Appeal. Don't let the elderly be on their own. Support this lonely old man by coming to hear him play his golden oldies every Thursday night at the Voodoo." I ask Terri if he still pogoes, and his eyes light up (well, his eye actually), and with a quick smile, up and down he bunts, like a kid on caffeine.
I make my way back to the Europa, once the most shelled hotel in the world, now a chic boutique. Along the way I pass the Albert Clock, which lists like the leaning tower of Pisa. It not only has the inclination, it has the time.
And I take a stop at the storied Ulster Hall, the Grand Dame of Bedford Street, where if the walls could talk, they wouldn't talk, they would sing. Glenn Miller performed for American Troops stationed in Belfast preparing for the Normandy invasion of 1944 (a local saw at the time: The Americans are "oversexed, overpaid and over here; the Brits are undersexed, underpaid, and under Eisenhower); Paul Robeson bellowed Old Man River here. The Rolling Stones, in 1964, played their shortest set, 13 minutes, before hysterical fans broke up the show. Led Zeppelin debuted Stairway to Heaven here in 1971 to an unimpressed audience. The Clash were due to play in 1977, but when insurance was cancelled for the gig, hundreds of disappointed fans rioted. Terri Hooley said it may have been "the only riot of the Troubles where Catholics and Protestants were fighting on the same side."
That evening its back to Waterfront Hall, this time for a concert celebrating the man who threw a net across the world with his poetry, Seamus Heaney, the Nobel Prize winner who died in August 2013 at 74. His final message to the world, van cleef bracelet knock off written in Latin just minutes before he passed: 'Noli timere', "Don't be afraid."
The main presenter is Belfast born actor Stephen Rea (were you surprised in The Crying Game?), who enjoyed a 35 year relationship with Seamus. They both served as directors of the Field Day Theatre company, which they saw as a "direct intervention" of art and culture during The Troubles.
There is a theory of "primitive affluence" that suggests that when a society has its primary needs met by Nature food, shelter, clothing then it will turn to creativity. Bali, a tropical island in Indonesia where the rich volcanic soil produces an abundance of food and materials for fabrics and building, is held as an example. The trope is that "everyone in Bali is an artist." Yet, while it is true that most everyone spends days carving, painting and dancing, there is very little originality in the products all are variations on a standard theme, precisely ritualistic, all expressed within rigid boundaries. The island's most famous dance, Kecak, was created by a German painter and musician, in the 1930s, intended as a performance for tourists.
On the other side of the field, Malcolm Gladwell, the counter intuitive craftsman, in his book David and Goliath: Underdogs, Misfits, and the Art of Battling Giants, promotes the idea of "desirable difficulty," wherein disadvantages propel people to extraordinary achievement and creativity.
Northern Ireland may be the poster child for Mr. Gladwell's theory. About the size of Connecticut, with less than half the population (about 2 million people), it has a wildly disproportionate number of fearless creatives and original thinkers. Yes, it is as far from "primitive affluence" as can be found. The land has few natural resources. Everything from coal to timber to iron has to be imported. For much of the year, the weather is cold and dank. And, for years, the region endured ethno nationalist and sectarian strife. One rumor has it that when archeologists broke into King Tut's tomb they found a newspaper with the headline, "Irish Problems Still Unsolved."
The exceedingly carbonated era that began in 1969, known as The Troubles, ended with the Good Friday Agreement of April 10, 1998, an accord that brought the Peace Dividend, a surge in cathexis with the land, and the beginnings of a surprising renaissance.
Yet, throughout its fractious history Northern Ireland has continued to unleash unreasonable creativity. The Kelvin scale was invented by a Belfastian; the ejection seat, portable defibrillator, modern tractor, the safety lamp for miners and chocolate milk by engineers from County Down. It could be argued distilled whiskey was concocted here, as the flush toilet.
On the entrepreneurial side, Northern Ireland, despite its challenges, became the largest linen producer in the world. And had the largest ropeworks. It was the largest manufacturer of fizzy drinks; largest shirt maker; had the largest flax machine works; largest tobacco factory; largest handkerchief factory in the world. For a time, a century ago, it was the world's leading industrial city, anchored by the biggest shipyard in the world, and there it created the biggest man made moving object in history: the ocean liner Titanic.
And then the arts. Lewis, Jack Higgins (who was raised here), Oscar Wilde (who schooled in County Fermanagh), Sir Kenneth Branagh, Patrick Magee, Sam Neill, Liam Neeson, and the most famous film star of the land, The DeLorean. There is not so much sun in this northern clip of the world, so folks are often inside sipping the hot cup of creativity, fanning the flames of magic turf.
When I read, then, that one of my teenage heroes, Van Morrison, was being awarded "The Freeman of Belfast" honor (which allows him to drive his herd of sheep through the center of town), I knew I had to go and jump into this place.
So well I remember standing on the sidelines at a high school mixer, too shy to cross the room and make the ask. But when Gloria, performed by Them (named for the 1954 horror movie about giant radioactive ants) with the deep burr of Van Morrison's voice slashing through paper walls, came on the record player, I found a beat and a gift of confidence I never knew I had, and strutted across the floor and asked the most beautiful girl to dance. And she said, "yes."
I won't commit the crime of clich and say his songs were the soundtrack of my life, but there were milestones marked in the Druidic forest trails of his music. "Moondance," for instance, enabled my own passage to freemanhood, and I'm sure I am not alone in that refrain.
With the first bite of fall I make the pilgrimage to Northern Ireland, to Belfast, where Van Morrison, after a life time of travel, and living in the artistic meccas of Woodstock and Marin County, has come home, to the place he was born.
I make my way to Waterfront Hall, and settle in just below Violet Morrison, Van's mom, in the balcony. It's a family affair, as the chief back up singer is Van's daughter, Shana.
Silence, anticipation seem in command. Then The Lord Mayor Mirtn Muilleoir takes the mic, and says, "He united us in the past, he's united us tonight and he will unite us in the future. This honor represents our love, respect and gratitude for Van Morrison from the 'dark side of the street to the bright side of the road'."
And Van the Freeman, six time Grammy winner, sporting signature dark suit, black hat and sunglasses, struts out stage left and gives a thumbs up to the crowd. He signs a special scroll, accepts a gold key to the city, bows, and then, without a word, picks up his alto sax, and launches into a sensual Celtic Swing.
And from there into "Moondance," "Brown Eyed Girl," and a roll call of greats, many citing patches of his personal map, sign posts and street names from his East Belfast boyhood. Van, of course, remains rock's foremost curmudgeon, and true to form he lets the music do the talking, rarely speaking, sometimes turning his back to the audience to play.
But at 68, after 50 years as a fiercely prolific copy van cleef pendant artist, he still summons the nerve to sing about the world as if it remains to be made, or as if it could be unmade, something he's witnessed in his hometown. As so many in Northern Ireland, he rattles the door of convention in its frame. And as he growls his lines, making himself into a sea monster, his daughter Shana swoops over him and digs van cleef bracelet replica into the songs, adding fervor in a glittering dress.
Just before Into the Mystic, The Belfast Cowboy sits down and jests: "This is the part where I hide behind the piano." A German journalist next to me, who has been to a score of Van's concerts, turns to me shocked and says "that's the most he's ever said at a concert." Then the piano takes off, like a boat untied, into waves of melody. There is the feeling that Van is looking back at his dock from a future already passed.
This is a "hand of history" moment in Belfast. We're immersed in something called "yarragh," fleeting elusive moments of transcendence, when the sense of an unrepeatable event is present. Like the city itself, this is an irresolvable adventure, someplace between the breaks and holes in the music.
He ends the municipal tribute with a muscle and fiber rendition of "Gloria," and I am transported back, as no doubt many in the audience, to teendom, to that moment when we loosed ourselves from words and floated on the bowers of his music.
Van is now a Freeman of Belfast, which is doubly significant, as just a few years ago men were not free to walk this city, and now they are.
The day after the concert I head out to meet another cyclone in residence, Terri Hooley, the "godfather of punk," at the latest awakening of his record shop, Good Vibrations, with its 1955 Elvis effigy out front. He is still, after all these years, hawking vinyl, posters, and the trending whiffs of the '70s. He insists we head over to the pub for a pint of Guinness with a brandy chaser, his preferred poison for the last half century. He lost an eye with a stray arrow as a boy, and has a reputation for plucking out his glass eye and dropping it into a drink, so I keep my pint out of reach. After a sip or few he shares, "I honestly believe punk bands saved countless lives, keeping impressionable young people away from the paramilitaries and giving us all something exciting to focus on."
Terri Hooley first opened his record shop on Great Victoria Street in 1976, at the time the most bombed piece of real estate in the world. It quickly became a safe haven, a neutral harbor, at a time when things were very thin on the ground. Teens and lost tribes from all sections and classes, from both sides of the divide, joined by a love of music, hung out in peace, preferring tunes to stones, music and culture more than the dead hand of sectarianism. It was a firefly of light in the blackness of Belfast at the time.
Though a Hank Williams fan in a polo neck, when he heard Punk it screeched his being. "To be a punk was to be different from the past." He started his own label, and produced edgy, alternative records. "Teenage Kicks," by the Undertones, was his biggest hit. He took the record to London and pedaled it around, but no one bit. "They said it was the worst record they ever heard in their lives." Then John Peel, the rock star DJ, played it on the BBC, twice, in a row, and the Undertones were signed to a major label. Hooley never did it for the money his store has gone bankrupt more times than the airlines and he still doesn't have any savings, but his unending efforts to build peace through music are recognized now around the world. "My brother was addicted to heroin; I'm addicted to having a record shop."
"For such a small population we have more talent per head of poets, painters and performers than anywhere else in Europe. Because of our in between status the arts give young people something to be proud of. It proves to every kid here that he can achieve something, and have a bloody good laugh doing it." Terri Hooley
Terri has a sign in his store at the top of the stairs, "Help the Aged Appeal. Don't let the elderly be on their own. Support this lonely old man by coming to hear him play his golden oldies every Thursday night at the Voodoo." I ask Terri if he still pogoes, and his eyes light up (well, his eye actually), and with a quick smile, up and down he bunts, like a kid on caffeine.
I make my way back to the Europa, once the most shelled hotel in the world, now a chic boutique. Along the way I pass the Albert Clock, which lists like the leaning tower of Pisa. It not only has the inclination, it has the time.
And I take a stop at the storied Ulster Hall, the Grand Dame of Bedford Street, where if the walls could talk, they wouldn't talk, they would sing. Glenn Miller performed for American Troops stationed in Belfast preparing for the Normandy invasion of 1944 (a local saw at the time: The Americans are "oversexed, overpaid and over here; the Brits are undersexed, underpaid, and under Eisenhower); Paul Robeson bellowed Old Man River here. The Rolling Stones, in 1964, played their shortest set, 13 minutes, before hysterical fans broke up the show. Led Zeppelin debuted Stairway to Heaven here in 1971 to an unimpressed audience. The Clash were due to play in 1977, but when insurance was cancelled for the gig, hundreds of disappointed fans rioted. Terri Hooley said it may have been "the only riot of the Troubles where Catholics and Protestants were fighting on the same side."
That evening its back to Waterfront Hall, this time for a concert celebrating the man who threw a net across the world with his poetry, Seamus Heaney, the Nobel Prize winner who died in August 2013 at 74. His final message to the world, van cleef bracelet knock off written in Latin just minutes before he passed: 'Noli timere', "Don't be afraid."
The main presenter is Belfast born actor Stephen Rea (were you surprised in The Crying Game?), who enjoyed a 35 year relationship with Seamus. They both served as directors of the Field Day Theatre company, which they saw as a "direct intervention" of art and culture during The Troubles.
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6. NOTES: With the release of running back Nic Grigsby, Ottawa will go with Canadians Kienan LaFrance and Brendan Gillanders against Montreal . . . Defensive backs Abdul Kanneh and Tristan Jackson as well as offensive.
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6. NOTES: With the release of running back Nic Grigsby, Ottawa will go with Canadians Kienan LaFrance and Brendan Gillanders against Montreal . . . Defensive backs Abdul Kanneh and Tristan Jackson as well as offensive.
Riders' Canadian content is improvingMarch 16, 2017
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Van Heeren's legal marathon keeps on running
The New Zealand Herald11:10pm Wed 24 MayNetworkHelp SupportFormer partner still awaiting payout, despite winning in court.
L to R, Alex van Heeren, Catriona Williams and Stephanie Iremonger. Photo / Norrie Montgomery.
Huka Lodge, one of New Zealand's best known luxury retreats, is at the heart of an acrimonious dispute between 69 year old Alex van Heeren and 74 year old Michael Kidd.
The two businessmen have had a marathon 20 year court battle in New Zealand and South Africa over Huka Lodge and a number of other assets.
The courts have found in favour of Kidd and ordered van Heeren to pay US$25 million ($37 million) plus costs.
Van Heeren claims he cannot pay the US$25 million because most of his assets have been transferred to tax haven based entities over which he has no control.
The story goes back to the mid 1970s, when British born Kidd and Dutch born van Heeren worked for a steel trading company in Johannesburg. In 1975 they set up their own steel trading company and in 1979 they formed Genan Trading in the Netherlands Antilles, a Caribbean tax haven. The formation of the company was effected in the Netherlands, with Kidd and van Heeren holding 50 per cent each.
Genan generated huge cash surpluses from steel trading based on Kidd's trading expertise while van Heeren looked after the company's finances.
In the early 1980s, the two shareholders, who were concerned about the political situation in South Africa, decided to emigrate to New Zealand under our "entrepreneurial scheme". They were both granted residency and purchased homes in Auckland. They also acquired a New Zealand company, Prime International Ltd.
Van Heeren moved to New Zealand in 1981 but Kidd stayed in South Africa because Genan Trading and a number of jointly owned South African companies continued to operate in the African country. Kidd moved back to the United Kingdom in 1987 to replica hermes handbags be closer to his family.
Van Heeren wasted no time in New Zealand. He was captivated by Huka Lodge when he saw it for the first time from the footbridge over the Huka Falls.
The Dutchman was appointed Honorary Consul for The Netherlands in Auckland in 1985, a position he held until 2012.
Van Heeren now gives his home address in Belgium, where he is the Honorary Consul for New Zealand to a number of Belgian provinces.
Meanwhile, back in the 1980s van Heeren purchased a significant shareholding in Wellesley Resources, one of the high flying NZX property companies in the mid 1980s. He sold the stake for $30 million just three months before the 1987 sharemarket crash. The Wellesley investment demonstrated that van Heeren fake hermes leather handbags was an astute investor.
However, the two partners began to have major disagreements in the late 1980s. In 1991 they finalised an agreement how much is a hermes handbag in South Africa to terminate their relationship and divide their business assets. This agreement has been at the centre of their bitter dispute.
Meanwhile, van Heeren continued to expand his New Zealand business network. In 1993 he obtained a 9.1 per cent shareholding in the Fay, Richwhite consortium that purchased New Zealand Rail from the Crown.
New Zealand Rail changed copy hermes bags its name to Tranz Rail and listed on the NZX. In 1998 van Heeren sold his shares for a profit of more than $42 million, just before Tranz Rail's share price crashed.
In February 1996 Kidd filed proceedings in New Zealand challenging aspects of his 1991 agreement with van Heeren.
The New Zealand Herald11:10pm Wed 24 MayNetworkHelp SupportFormer partner still awaiting payout, despite winning in court.
L to R, Alex van Heeren, Catriona Williams and Stephanie Iremonger. Photo / Norrie Montgomery.
Huka Lodge, one of New Zealand's best known luxury retreats, is at the heart of an acrimonious dispute between 69 year old Alex van Heeren and 74 year old Michael Kidd.
The two businessmen have had a marathon 20 year court battle in New Zealand and South Africa over Huka Lodge and a number of other assets.
The courts have found in favour of Kidd and ordered van Heeren to pay US$25 million ($37 million) plus costs.
Van Heeren claims he cannot pay the US$25 million because most of his assets have been transferred to tax haven based entities over which he has no control.
The story goes back to the mid 1970s, when British born Kidd and Dutch born van Heeren worked for a steel trading company in Johannesburg. In 1975 they set up their own steel trading company and in 1979 they formed Genan Trading in the Netherlands Antilles, a Caribbean tax haven. The formation of the company was effected in the Netherlands, with Kidd and van Heeren holding 50 per cent each.
Genan generated huge cash surpluses from steel trading based on Kidd's trading expertise while van Heeren looked after the company's finances.
In the early 1980s, the two shareholders, who were concerned about the political situation in South Africa, decided to emigrate to New Zealand under our "entrepreneurial scheme". They were both granted residency and purchased homes in Auckland. They also acquired a New Zealand company, Prime International Ltd.
Van Heeren moved to New Zealand in 1981 but Kidd stayed in South Africa because Genan Trading and a number of jointly owned South African companies continued to operate in the African country. Kidd moved back to the United Kingdom in 1987 to replica hermes handbags be closer to his family.
Van Heeren wasted no time in New Zealand. He was captivated by Huka Lodge when he saw it for the first time from the footbridge over the Huka Falls.
The Dutchman was appointed Honorary Consul for The Netherlands in Auckland in 1985, a position he held until 2012.
Van Heeren now gives his home address in Belgium, where he is the Honorary Consul for New Zealand to a number of Belgian provinces.
Meanwhile, back in the 1980s van Heeren purchased a significant shareholding in Wellesley Resources, one of the high flying NZX property companies in the mid 1980s. He sold the stake for $30 million just three months before the 1987 sharemarket crash. The Wellesley investment demonstrated that van Heeren fake hermes leather handbags was an astute investor.
However, the two partners began to have major disagreements in the late 1980s. In 1991 they finalised an agreement how much is a hermes handbag in South Africa to terminate their relationship and divide their business assets. This agreement has been at the centre of their bitter dispute.
Meanwhile, van Heeren continued to expand his New Zealand business network. In 1993 he obtained a 9.1 per cent shareholding in the Fay, Richwhite consortium that purchased New Zealand Rail from the Crown.
New Zealand Rail changed copy hermes bags its name to Tranz Rail and listed on the NZX. In 1998 van Heeren sold his shares for a profit of more than $42 million, just before Tranz Rail's share price crashed.
In February 1996 Kidd filed proceedings in New Zealand challenging aspects of his 1991 agreement with van Heeren.
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Vans Takes Big Step Up in Earnings After Going Public
ORANGE Vans Inc., a maker of sneakers, reported $6.5 million in earnings for its first fiscal year as a publicly traded company.
If not for onetime charges related to its August, 1991, public stock offering, the company said, it would have posted a profit of $9.6 million, or $1.07 a share, for the fiscal year ended May 31. Earnings per share for the year came to 72 cents.
The latest results contrast with a loss of $236,000 for the previous fiscal year. Since Vans was not publicly traded at that time, earnings per share were not disclosed.
Sales for the latest fiscal year came to $91.2 million, a 28.4% increase from $70.2 million in the previous 12 months.
"Our record sales and earnings during a period how much is a hermes handbag of prolonged nationwide recession were particularly gratifying," said Richard P. Leeuwenburg, Vans president.
Despite the gains for the year, the Orange based company noted that its fourth quarter results were weaker than expected. Leeuwenburg blamed the sluggish California economy, the Los Angeles riots and fake hermes leather handbags weakness in the retail markets of Mexico, Europe and Japan.
Earnings were $3.4 million, or 35 cents a share, in the fourth quarter, compared with a loss of $1.3 million in the corresponding period last year. Sales were $25 million, up 16.4% from $21.4 million.
Vans stock, which trades on the NASDAQ market, closed Thursday, fake Hermes bag maintenance a day after the company released its earnings statement, at $11.25 a share, up 75 cents.
Leeuwenburg said the company faces more difficult times.
"The weak economic picture for the important markets in which Vans sells will have an adverse copy hermes bags impact on sales at least through the balance of the quarter," he said. "However, longer term, our outlook remains very positive."
ORANGE Vans Inc., a maker of sneakers, reported $6.5 million in earnings for its first fiscal year as a publicly traded company.
If not for onetime charges related to its August, 1991, public stock offering, the company said, it would have posted a profit of $9.6 million, or $1.07 a share, for the fiscal year ended May 31. Earnings per share for the year came to 72 cents.
The latest results contrast with a loss of $236,000 for the previous fiscal year. Since Vans was not publicly traded at that time, earnings per share were not disclosed.
Sales for the latest fiscal year came to $91.2 million, a 28.4% increase from $70.2 million in the previous 12 months.
"Our record sales and earnings during a period how much is a hermes handbag of prolonged nationwide recession were particularly gratifying," said Richard P. Leeuwenburg, Vans president.
Despite the gains for the year, the Orange based company noted that its fourth quarter results were weaker than expected. Leeuwenburg blamed the sluggish California economy, the Los Angeles riots and fake hermes leather handbags weakness in the retail markets of Mexico, Europe and Japan.
Earnings were $3.4 million, or 35 cents a share, in the fourth quarter, compared with a loss of $1.3 million in the corresponding period last year. Sales were $25 million, up 16.4% from $21.4 million.
Vans stock, which trades on the NASDAQ market, closed Thursday, fake Hermes bag maintenance a day after the company released its earnings statement, at $11.25 a share, up 75 cents.
Leeuwenburg said the company faces more difficult times.
"The weak economic picture for the important markets in which Vans sells will have an adverse copy hermes bags impact on sales at least through the balance of the quarter," he said. "However, longer term, our outlook remains very positive."
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Super fun morning at West Van Run includes Zipper
Before saluting speedsters Kevin van cleef necklace knock off Friesen, Sabrina Wilkie and Catherine Watkins, or the super fun people dressed in costumes for West Van Run's 5K on sunny, snow less Saturday, we need to discuss Zipper gate.
If you ever have this crazy idea of dressing up as a Ninja Turtle, for example, and you have a one piece outfit with no zippers or escape hatches, and you've drank tons of water all morning and you skip using the washroom before the starting gun, this will become an issue. Trust me!
About 2.5K in to the scenic race, which attracted 608 runners this year, my focus on a personal best time became oh so irrelevant to finding a washroom in record time.
I veered off course for the waterfront Silk Purse Studio and, in a panicked mode, asked two women who were working on paintings to let this sweating stranger use their private washroom. Fortunately one of the women understood it was time to make an exception or brace for a turtle tsunami! Cowabunga, indeed!
It took forever to get out of the costume, then back in, and back to the race course. The awesome women my super heroes of the day even attached the padded shell back on my outfit before joking "please visit again, Mr. Turtle!"
OK, some people might have been devastated by this unexpected but are there any expectations for a turtle to reach the finish line early?
Speaking of real zippers, as in zipping right by, Kevin Friesen won the 5K in 14:48, edging out Rob Watson (14:55) and Theo Hunt (14:48). The top six finished in under 16 minutes, and the top 25 in under 18, which is pretty impressive.
Sabrina Wilkie and Catherine Watkins finished tied on the clock for first in the women's category with course record 17 minute efforts, but Wilkie actually won the race by a hair after an epic sprint battle to the tape. Kirsten Lee was van cleef necklace alhambra imitation third in 17:24.
A number of runners reported personal bests or improved performances on this year's course, which started in front of West Van Community Centre and finished in Dundarave Park. Special Olympics (North Shore) and Debra Kato's costume closet! Ms. Kato, dressed in a Deadpool outfit, was difficult to miss on the course, especially with her pirate hatchet thingy waving around!
There were a lot of capes, lots of glitter, lots of Supermen and Superwomen, Spider Men, the Flash, Avengers, Batmen, Wonder Women and a Super Babe (hi Judy!).
The kids' races at Dundarave Park were entertaining as always, as were the number of vendor displays.
West Van Run blogger Bradley Cuzen, who ran the 5K in a relaxed 23:01 without the "interesting" Superman costume used to promote this event, gave in to pre race requests to see it. He changed into the "hero" right in the middle of the community centre lobby. Apparently, this is the downside of not having phone booths anymore!
A number of the club's top athletes skipped the run to work as volunteers and they were great. Bubbly Marg Coe was a high five factory. The excellent "cheer station" at the 3K mark brought instant smiles, especially the girl holding the 'Why walk when you can cartwheel?' sign. She had a walking boot/brace on her left foot!
NDP candidate and longtime North Shore resident Mehdi Russel hoping to win the West Vancouver Capilano riding in May provincial election, worked the crowd and asked if we could take a together. He handed me his business card and brochure even though I pointed out I had no pockets or zippers!
At the finish line I chatted with vendors and was handed 2 bottles of water, Honey Water, 2 Muscle Mlk bottles and a large coffee. I consumed all of them by the time I walked back to the starting line along Marine Drive in my turtle outfit to fetch the car.
En route home to Langley, and just before the Port Mann Bridge, guess who really had to go to the washroom again? Rest in peace turtle suit!
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Before saluting speedsters Kevin van cleef necklace knock off Friesen, Sabrina Wilkie and Catherine Watkins, or the super fun people dressed in costumes for West Van Run's 5K on sunny, snow less Saturday, we need to discuss Zipper gate.
If you ever have this crazy idea of dressing up as a Ninja Turtle, for example, and you have a one piece outfit with no zippers or escape hatches, and you've drank tons of water all morning and you skip using the washroom before the starting gun, this will become an issue. Trust me!
About 2.5K in to the scenic race, which attracted 608 runners this year, my focus on a personal best time became oh so irrelevant to finding a washroom in record time.
I veered off course for the waterfront Silk Purse Studio and, in a panicked mode, asked two women who were working on paintings to let this sweating stranger use their private washroom. Fortunately one of the women understood it was time to make an exception or brace for a turtle tsunami! Cowabunga, indeed!
It took forever to get out of the costume, then back in, and back to the race course. The awesome women my super heroes of the day even attached the padded shell back on my outfit before joking "please visit again, Mr. Turtle!"
OK, some people might have been devastated by this unexpected but are there any expectations for a turtle to reach the finish line early?
Speaking of real zippers, as in zipping right by, Kevin Friesen won the 5K in 14:48, edging out Rob Watson (14:55) and Theo Hunt (14:48). The top six finished in under 16 minutes, and the top 25 in under 18, which is pretty impressive.
Sabrina Wilkie and Catherine Watkins finished tied on the clock for first in the women's category with course record 17 minute efforts, but Wilkie actually won the race by a hair after an epic sprint battle to the tape. Kirsten Lee was van cleef necklace alhambra imitation third in 17:24.
A number of runners reported personal bests or improved performances on this year's course, which started in front of West Van Community Centre and finished in Dundarave Park. Special Olympics (North Shore) and Debra Kato's costume closet! Ms. Kato, dressed in a Deadpool outfit, was difficult to miss on the course, especially with her pirate hatchet thingy waving around!
There were a lot of capes, lots of glitter, lots of Supermen and Superwomen, Spider Men, the Flash, Avengers, Batmen, Wonder Women and a Super Babe (hi Judy!).
The kids' races at Dundarave Park were entertaining as always, as were the number of vendor displays.
West Van Run blogger Bradley Cuzen, who ran the 5K in a relaxed 23:01 without the "interesting" Superman costume used to promote this event, gave in to pre race requests to see it. He changed into the "hero" right in the middle of the community centre lobby. Apparently, this is the downside of not having phone booths anymore!
A number of the club's top athletes skipped the run to work as volunteers and they were great. Bubbly Marg Coe was a high five factory. The excellent "cheer station" at the 3K mark brought instant smiles, especially the girl holding the 'Why walk when you can cartwheel?' sign. She had a walking boot/brace on her left foot!
NDP candidate and longtime North Shore resident Mehdi Russel hoping to win the West Vancouver Capilano riding in May provincial election, worked the crowd and asked if we could take a together. He handed me his business card and brochure even though I pointed out I had no pockets or zippers!
At the finish line I chatted with vendors and was handed 2 bottles of water, Honey Water, 2 Muscle Mlk bottles and a large coffee. I consumed all of them by the time I walked back to the starting line along Marine Drive in my turtle outfit to fetch the car.
En route home to Langley, and just before the Port Mann Bridge, guess who really had to go to the washroom again? Rest in peace turtle suit!
{ phone }
{ addressPostalCode }
By clicking "Create Account", replica van cleef gold clover necklace I hearby grant permission to Market to use my account information to create my account.
I also accept and agree to be bound by Postmedia's Terms and Conditions with respect to my use of the Site and I have read and understand Postmedia's Privacy Statement. I consent to the collection, use, maintenance, and disclosure of my information in accordance with the Postmedia's Privacy Policy.
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