text:
Compress JPG online here for free
When you scan the documents to send them via email or upload to the website, the file size can be very big for that. It will lead to many inconveniences. For example, someone has a very slow internet connection it will take him very long to download the image or document. Another issue is the limited file size to send via email or upload to the website. How to solve these problems? Simply use http://compressjpg.online/ to compress any JPG image which is also optimzed for being used at a website.
What are the benefits of this JPG compression service?
Perfect quality. Reduce your images or scanned JPG files by up to 60%. This size is ideal for downloading and uploading the file throughout the Internet and sending by email. It will also guarantee fast loading times of the webpage you are using the image for. At the same time, it will be absolutely readable and of the highest quality. Convenient to use.
Just upload your file, wait a few seconds for the compression to finish, and download with one click. It's a quick and safe process.


text:
It's that time of year again, where we raffle off a sewing machine to raise funds for our favorite charities.
This year we are raffling off an Elna 220 Explore in support of our favorite animal rescues. CLICK HERE to get your tickets now! GOOD LUCK!
Pattern of the week
Merri Blouse Sewing Pattern
We have had such an amazing to or new blouse sewing pattern. It's easy and stylish. If you haven't got yours yet CLICK HERE to get yours now!
This week's pattern for subscribers
Workout mini shorts
These shorts are cute and comfortable, and the sewing pattern is going out to our subscribers this Friday! If you're not yet a subscriber SIGN UP TODAY to receive 10 sewing patterns a month from only $1.99
Tutorial of the week
Create your own day planner
We have created a sewing tutorial for this gorgeous day planner just for you. CLICK HERE to download your free tutorial, and pattern as well printable 2017 diary pages to insert into your brand new day planner.
What you need:
2 x sheets thick A4 Cardboard
0.75 meters / 0.9 yards of thick woven fabric
A spring clip file mechanism
2 x 10mm eyelets with washers

subset: commoncrawl


text:
Key Points
Kdm2b insufficiency promotes the initiation of T-ALL.
KDM2B in PRC1.1 antagonizes NOTCH1 and functions as a tumor suppressor.
Visual Abstract
KDM2B together with RING1B, PCGF1, and BCOR or BCORL1 comprise polycomb repressive complex 1.1 (PRC1.1), a noncanonical PRC1 that catalyzes H2AK119ub1. It binds to nonmethylated CpG islands through its zinc finger-CxxC DNA binding domain and recruits the complex to target gene loci. Recent studies identified the loss of function mutations in the PRC1.1 gene, BCOR and BCORL1 in human T-cell acute lymphoblastic leukemia (T-ALL). We previously reported that Bcor insufficiency induces T-ALL in mice, supporting a tumor suppressor role for BCOR. However, the function of BCOR responsible for tumor suppression, either its corepressor function for BCL6 or that as a component of PRC1.1, remains unclear. We herein examined mice specifically lacking the zinc finger-CxxC domain of KDM2B in hematopoietic cells. Similar to Bcor-deficient mice, Kdm2b-deficient mice developed lethal T-ALL mostly in a NOTCH1-dependent manner. A chromatin immunoprecipitation sequence analysis of thymocytes revealed the binding of KDM2B at promoter regions, at which BCOR and EZH2 colocalized. KDM2B target genes markedly overlapped with those of NOTCH1 in human T-ALL cells, suggesting that noncanonical PRC1.1 antagonizes NOTCH1-mediated gene activation. KDM2B target genes were expressed at higher levels than the others and were marked with high levels of H2AK119ub1 and H3K4me3, but low levels of H3K27me3, suggesting that KDM2B target genes are transcriptionally active or primed for activation. These results indicate that PRC1.1 plays a key role in restricting excessive transcriptional activation by active NOTCH1, thereby acting as a tumor suppressor in the initiation of T-cell leukemogenesis.
Polycomb group proteins compose multiprotein complexes named polycomb repressive complexes (PRCs), which play an important role in the transcriptional repression of target genes through histone modifications. Two major PRCs have been characterized: PRC1 (or canonical PRC1), which catalyzes monoubiquitination at lysine 119 of histone H2A (H2AK119ub1), and PRC2, which catalyzes mono-, di-, and trimethylation at lysine 27 of histone H3 (H3K27me3). These 2 complexes function cooperatively through the recognition of PRC2-induced H3K27me3 by CBX, a core subunit of canonical PRC1.1,2 In contrast, recent studies revealed that variant or noncanonical PRC1 complexes catalyze H2AK119ub1 without prior H3K27me3 induced by PRC2 and recruit PRC2 to monoubiquitinated loci.3
KDM2B (also known as FBXL10, NYD1, and JHDM1B) is a JmjC domain containing H3K36me2 demethylase, and functions as a component of PRC1.1, which is categorized as noncanonical PRC1.4 KDM2B binds to nonmethylated CpG islands (CGIs) through its zinc finger-CxxC (ZF-CxxC) DNA-binding domain as most mammalian polycomb target sites are associated with CGIs.5,6 The ZF-CxxC domain-mediated recognition of unmethylated CGIs leads to the recruitment of other components of PRC1.1 through the cooperation of PCGF1 and BCOR/BCORL1.7-9 Because CGIs are frequently located around transcription start sites (TSS), including most housekeeping genes and developmental regulator genes,10,11 PRC1.1 is considered to play an important role in the regulation of these genes. The deletion of the KDM2B ZF-CxxC domain induced the complete loss of KDM2B occupancy and removal of PCGF1 from CGIs, and mice lacking the KDM2B ZF-CxxC domain showed embryonic lethality because of developmental cessation.12 In the development of the hematopoietic system, KDM2B also plays a critical role in the maintenance of hematopoietic stem and progenitor cells (HSPCs) and lymphopoiesis through the regulation of hematopoietic and lymphoid development-associated genes.13 We also demonstrated that the forced expression of Kdm2b prevented the exhaustion of the long-term repopulating potential of hematopoietic stem cells (HSCs) following serial transplantation by negatively regulating the expression of cyclin-dependent kinase inhibitor genes, such as Ink4a.14
Somatic mutations in polycomb group and associated genes are frequently detected in patients with T-cell malignancies. Loss-of-function mutations in PRC2 component genes, such as EZH2, EED, and SUZ12, have frequently been found in pediatric and adult T-cell acute lymphoblastic leukemia (T-ALL) patients.15-19 Previous studies also demonstrated that an Ezh2 deficiency induced T-ALL in mouse models.20-23 A previous study based on human and mouse T-ALL cells revealed that the activation of NOTCH1 specifically induced the loss of H3K27me3 by antagonizing the activity of PRC2.16 These findings indicated that PRC2 plays a tumor suppressive role in T-cell leukemogenesis. Loss-of-function mutations in BCOR and its homolog BCORL1, components of PRC1.1, have also been detected in several T-cell malignancies, such as extranodal natural killer/T-cell lymphoma,24 T-cell prolymphocytic leukemia,25 and T-ALL.19,26 We previously generated mice deficient for Bcor exon 4 (BcorΔE4/y) lacking a region of the Bcl6-binding domain and found that these mice developed T-ALL mostly in a NOTCH1-dependent manner.27 Mice deficient for Bcor exons 9 and 10 (BcorΔ9-10/y) lacking the PCGF1-binding domain also developed T-ALL.28 These findings suggest that BCOR also plays a tumor-suppressive role in T-cell leukemogenesis. However, the expression of Bcor without exons 9 and 10 was significantly reduced at both the messenger RNA and protein levels, similar to BCOR mutants in MDS patients,29 suggesting that the corepressor function of BCOR for BCL6 was also attenuated.28 Therefore, the function of BCOR responsible for tumor suppression, either the corepressor function for BCL6 or that as a component of PRC1.1, remains unclear.
In the present study, we analyzed mice lacking the ZF-CxxC domain of KDM2B, a core component of PRC1.1, and found that they developed T-ALL in a similar manner to Bcor insufficient mice, suggesting a critical tumor suppressor role for PRC1.1 in the pathogenesis of T-cell leukemogenesis.
Materials and methods
Mice and generation of hematopoietic chimeras
The conditional Kdm2b allele (Kdm2bfl), which contains LoxP sites flanking Kdm2b exon 13 encoding the ZF-CxxC domain,12 was used. Kdm2bfl mice were backcrossed at least 6 times with C57BL/6 (CD45.2) mice. Mice were crossed with Rosa26::Cre-ERT mice (TaconicArtemis) to generate conditional Kdm2b knockout mice. To generate hematopoietic cell-specific Kdm2b knockout mice, we transplanted Kdm2bwt/wt;Cre-ERT or Kdm2bfl/fl;Cre-ERT total bone marrow (BM) cells into lethally irradiated CD45.1 recipient mice and deleted Kdm2b 4 weeks after transplantation by intraperitoneally injecting 100 μL of tamoxifen dissolved in corn oil at a concentration of 10 mg/mL for 5 sequential days. Littermates were used as controls. C57BL/6 mice congenic for the Ly5 locus (CD45.1) were purchased from Sankyo-Laboratory Service. All animal experiments were performed in accordance with our institutional guidelines for the use of laboratory animals and approved by the Review Board for Animal Experiments of Chiba University (approval ID: 30-56) and Tokyo University (approval ID: PA18-01).
Statistical analysis
Statistical analyses were performed using GraphPad Prism version 7. The significance of differences in continuous variables was measured by the Student t test. Survival curves were calculated by the Kaplan-Meier method and compared using the log-rank test. Data are shown as the mean ± standard error of the mean (SEM). Significance was taken at values of *P < .05; **P < .01; and ***P < .001.
Hematopoietic cell-specific deletion of Kdm2b in mice
We used Kdm2b floxed mice that harbored LoxP sites flanking Kdm2b exon 13 encoding the ZF-CxxC domain (Kdm2bfl)12 in the present study. We crossed them with Rosa26::Cre-ERT (Cre-ERT) mice. To assess the effects of Kdm2b insufficiency specifically in hematopoietic cells, we transplanted total BM cells from Kdm2bwt/wt;Cre-ERT (WT) and Kdm2bfl/fl;Cre-ERT CD45.2 female mice into lethally irradiated CD45.1 recipient female mice without competitor cells. Tamoxifen was injected intraperitoneally 4 weeks after transplantation to activate Cre. We hereafter refer to recipient mice reconstituted with WT and Kdm2bΔCxxC/ΔCxxC cells as WT and ΔCxxC mice, respectively (supplemental Figure 1A). We confirmed the complete deletion of Kdm2b exon 13 in hematopoietic cells from ΔCxxC mice by genomic polymerase chain reaction (PCR; supplemental Figure 1B). An RNA-sequencing (RNA-seq) analysis of lineage marker (Lin)−Sca-1+c-Kit+ (LSK) HSPCs revealed the specific deletion of Kdm2b exon 13 (supplemental Figure 1C). The removal of the ZF-CxxC exon generates a product that still associates with the PCGF1/PRC1.1 complex, but lacks its capacity to bind non-methylated DNA.12 We detected a truncated form of the KDM2B (KDM2BΔCxxC) protein at a lower level in ΔCxxC thymocytes than in WT in a western blot analysis (supplemental Figure 1D). The deletion of the ZF-CxxC domain did not affect the global levels of H2AK119ub1 or H3K27me3 (supplemental Figure 1E).
Deletion of Kdm2b ZF-CxxC impaired the repopulating capacity of HSPCs and lymphopoiesis
We examined hematopoiesis in ΔCxxC mice (Figure 1A). ΔCxxC mice exhibited leukocytopenia, mild anemia, and mild thrombocytosis in peripheral blood (PB) (Figure 1B). Leukocytopenia was mainly attributed to reductions in B and T lymphocytes (Figure 1C). A BM analysis 1 month after the tamoxifen treatment revealed significant decreases in the numbers of LSK HSPCs and lymphoid-primed multipotent progenitors (LMPPs) in ΔCxxC mice, whereas those of common myeloid progenitors and granulocyte-macrophage progenitors increased (Figure 1D). Spleen and thymus weights were not significantly different between WT and ΔCxxC mice (Figure 1E).
We then performed competitive BM transplantation assays. BM cells from WT or ΔCxxC CD45.2 female mice were transplanted into lethally irradiated CD45.1 recipient mice with the same number of CD45.1 competitor BM cells (supplemental Figure 2A). The chimerism levels of ΔCxxC cells in PB gradually declined, and ΔCxxC B and T cells were eventually outcompeted by competitor cells (supplemental Figure 2B). In contrast, ΔCxxC cells contributed to myeloid cells in the long term, albeit at a profoundly lower level than WT cells (supplemental Figure 2B). In a BM analysis 6 months after the tamoxifen treatment, ΔCxxC cells showed significantly lower chimerism levels in all lineages (particularly in B and T cells), LSK cells, LMPPs, and common lymphoid progenitors (CLPs) in BM and in thymocytes than WT cells, whereas chimerism levels in HSCs and myeloid progenitors were maintained in BM (supplemental Figure 2C). These results indicated that KDM2B plays an important role in the repopulation of hematopoiesis by HSCs, particularly repopulating lymphoid lineage cells.
Deletion of KDM2B ZF-CxxC–induced T-ALL
We next analyzed the pathophysiological impact of the deletion of KDM2B ZF-CxxC using WT and ΔCxxC mice in a noncompetitive BM transplantation setting (Figure 2A). Most ΔCxxC mice developed lethal T-ALL during the observation period of 300 days after the tamoxifen treatment in a similar manner to BcorΔE4 and BcorΔE9-10 mice27,28 (Figure 2B; supplemental Table 1). T-ALL mice showed the expansion of lymphoblasts, which were mostly CD4 and CD8 double positive (DP) (Figure 2B-C). The majority of mice exhibited thymomegaly and splenomegaly (Figure 2D) and had high chimerism levels of donor-derived T-ALL cells in their BM, spleen, thymus, and PB (Figure 2E). Because the majority of mice had an enlarged thymus and the expansion of T-ALL cells in the thymus, the origin of the disease was considered to be the thymus. We then examined whether the active NOTCH1 pathway was associated with the pathogenesis of T-ALL because Notch1 active mutations were frequently detected in T-ALL cells in BcorΔE4/y and BcorΔ9-10/y mice.27,28 Seven of 14 mice had frameshift or nonsense mutations in exon 34, which resulted in PEST domain truncations and the acquisition of resistance from FBXW7-mediated polyubiquitination.30 The remaining mouse had a missense mutation in exon 27, which was also associated with NOTCH1 activation through the destabilization of the connection between extracellular and intracellular domains30 (Figure 2F). Notch1 gene deletions (types 1 and 2), the other common mechanisms of NOTCH1 activation in murine T-ALL,31 were not detected in T-ALL mice (data not shown). We then performed a western blot analysis to evaluate the activation status of NOTCH1. Of interest, even the spleen cells from ΔCxxC T-ALL mice without Notch1 mutations listed in Figure 2F had a cleaved form of active NOTCH1 (Figure 2G), suggesting the presence of other Notch1-related active mutations. These results suggest that Kdm2b insufficiency collaborates with NOTCH1 activation to induce T-ALL.
KDM2B in PRC1.1 suppresses T-ALL development by antagonizing NOTCH1 activation
To clarify the molecular mechanisms underlying the development of T-ALL in ΔCxxC mice, we performed an RNA sequence analysis of DP leukemic cells from T-ALL mice and DP thymocytes from WT and ΔCxxC mice. RNA-seq analysis revealed that 324 and 1399 genes were upregulated (more than twofold) and 648 and 1632 genes were downregulated (more than twofold) in ΔCxxC DP thymocytes and DP leukemic cells, respectively, compared with WT DP thymocytes (supplemental Table 2A). A gene set enrichment analysis (GSEA) revealed the stronger enrichment of MYC target gene sets in ΔCxxC DP leukemic cells than in WT DP thymocytes (Figure 3A). Myc, a representative NOTCH1 target, was mildly upregulated in ΔCxxC DP thymocytes and strongly upregulated in ΔCxxC DP leukemic cells (Figure 3B-C). Although the expression of the direct target genes of NOTCH1 was not significantly altered in ΔCxxC DP thymocytes, they were upregulated in ΔCxxC DP leukemic cells, including Myc (Figure 3D; supplemental Table 2A), suggesting that NOTCH1 signaling is augmented in ΔCxxC T-ALL.
Next, we examined the possibility that the transformation has occurred at much earlier stages of T-cell development in the thymus. To this end, we analyzed CD4 and CD8 double-negative (DN) and DP cells 2 months after tamoxifen treatment (supplemental Figure 3). DN1-3 cells were significantly decreased in numbers in ΔCxxC mice compared with WT mice (Figure 3E-F), which could be attributed to the reduced numbers of lymphoid progenitors such as LMPPs and CLPs in BM (Figure 1D). In contrast, the numbers of DN4, DP, CD4+, and CD8+ cells in ΔCxxC mice recovered close to the WT levels (Figure 3E-F). Of note, the proportion of DN4 cells was significantly increased in ΔCxxC mice (Figure 3F), suggesting that ΔCxxC thymocytes acquired a growth advantage at around the DN4 stage. We then purified DN2 and DN3 cells from WT and ΔCxxC mice and cocultured them with TSt-4 stromal cells that express NOTCH ligand. Both DN2 and DN3 cells from ΔCxxC mice grew significantly better than those from WT mice (Figure 3G). RNA-seq of DN2, DN3, and DN4 cells from WT and ΔCxxC mice 2 months after tamoxifen injection revealed that the gene sets of NOTCH1 targets were specifically activated in ΔCxxC DN4 cells (Figure 3H; supplemental Table 2B). These results suggest that KDM2B loss enhanced proliferation of DN cells by augmenting the NOTCH1 signal.
We next performed serial transplantation assays to define the leukemia-initiating cells in this mouse model. We purified DN cells and DP cells in the thymus and total BM cells from ΔCxxC T-ALL mice and transplanted them into lethally irradiated recipient mice. All mice that were infused with DP cells or total BM cells from leukemic mice developed T-ALL within 1 month after transplantation (Figure 3I). Notably, 3 of 8 recipient mice infused with DN cells developed CD4+CD8+ T-ALL at around day 100 posttransplantation (Figure 3I). These results indicate that leukemic DP cells contain leukemia-initiating cells at a high frequency, but also suggest that DN cells are candidate cells of origin of tumor-initiating cells in this mouse model.
KDM2B target genes are transcriptionally active or primed for activation
We then performed a chromatin immunoprecipitation (ChIP)–seq analysis of KDM2B, H2AK119ub1, and H3K27me3 in thymocytes to identify KDM2B target genes. Because no anti-KDM2B antibodies were suitable for ChIP, we prepared mice expressing 3xFlag-KDM2B in hematopoietic cells by transducing HSCs with a 3xFlag-KDM2B virus followed by transplantation into lethally irradiated mice, and subjected total thymocytes containing DP thymocytes as the major cell population to a ChIP analysis using an anti-Flag antibody (supplemental Figure 4). A peak-calling analysis identified 6377 significant binding peaks of KDM2B. The majority of these peaks were located on the promoter region around TSS (TSS ± 2.0 kb) (Figure 4A; supplemental Table 3A). K-means clustering of the data around TSS revealed that the genes in cluster 1 showed the clear binding of KDM2B and colocalized with H2AK119ub1 and mostly with H3K27me3, indicating that these genes are targets of PRC1.1 (Figure 4B). Most of the target genes (cluster 1) were CGI genes defined by the UCSC Genome Browser (mm10) (Figure 4C), as expected from previous studies.5,6 We then compared H2AK119ub1, H3K27me3, and H3K4me3 modifications and RNA expression levels in each cluster in WT DP thymocytes. H2AK119ub1 levels were significantly higher in clusters 1 and 2 than in cluster 3, whereas H3K27me3 levels in cluster 2 were significantly higher than in the others. The enrichment of the H3K4me3+ histone mark was significantly and markedly stronger in clusters 1 and 2, respectively, than in cluster 3 (Figure 4D). RNA expression levels were significantly higher in cluster 1 than in the others (Figure 4E). These results suggest that KDM2B target genes are mainly repressed by H2AK119ub1 rather than H3K27me3, and many of the genes are already active or primed for activation by the H3K4me3 mark, which promotes transcription.
KDM2B in PRC1.1 suppresses T-ALL development by antagonizing NOTCH1 activation
We then compared the histone modification status at the promoter region (TSS ± 2.0 kb) in WT, ΔCxxC DP, and ΔCxxC T-ALL cells. H2AK119ub1 levels at promoters were significantly decreased in T-ALL cells, particularly at KDM2B target genes (cluster 1) (Figure 5A; supplemental Table 4A). Several NOTCH1 direct target genes, including Myc, lost H2AK119ub1 at promotors in T-ALL cells and similar results were observed in ΔCxxC DP cells (Figure 5B). We confirmed the binding of KDM2B to the promotor region of Myc, which appeared to be repressed mainly by H2AK119ub1, but not by H3K27me3, in DP thymocytes. Of note, H2AK119ub1 levels were reduced in ΔCxxC DP thymocytes and T-ALL cells (Figure 5C). A quantitative ChIP analysis confirmed the binding of KDM2B to the Myc promoter in DP thymocytes and significant reductions in H2AK119ub1 levels around the Myc promoter in ΔCxxC DP thymocytes and T-ALL cells (Figure 5D). The distribution of the ChIP-seq peaks of KDM2B in the present study, BCOR in WT thymocytes in our previous study27 and NOTCH1 in T-ALL cells32 closely overlapped at the promoter region (Figure 5E; supplemental Table 3A-C). We then compared H3K27me3 levels at promoters of cluster 1 genes and found that H3K27me3 levels were also significantly decreased in both T-ALL cells and ΔCxxC DP thymocytes (Figure 5F; supplemental Table 4B). Decreases in EZH2 binding peaks around TSS were significantly greater in ΔCxxC DP thymocytes than in WT DP thymocytes in cluster 1 genes (Figure 5G). EZH2 binding peaks in WT thymocytes also overlapped with KDM2B and NOTCH1 peaks (Figure 5H; supplemental Tables 3A, 3C, and 3D), suggesting that noncanonical PRC1.1 and PRC2 coordinately antagonized NOTCH1-driven transcription in thymocytes. The KEGG pathway analysis of 1276 genes, which had all peaks (Figure 5H), designated as overlapping genes, showed the significant enrichment of T-cell receptor signaling, NOTCH1 signaling, and the cell-cycle pathway, which plays an important role in the development of T-ALL (Figure 5I). The H3K27me3 levels of the overlapping genes in WT DP thymocytes were markedly lower than the 1182 EZH2 target genes without KDM2B and NOTCH1 binding in Figure 5H (designated as EZH2 only), whereas H3K4me3 levels showed an inverse relationship (Figure 5J). These results again indicate that PRC1.1 target genes are already more active or primed for activation by the H3K4me3 mark than EZH2 target genes without PRC1.1 and include many of the NOTCH1 direct target genes.
Role of KDM2B in the maintenance of T-ALL
Our study indicates that KDM2B in PRC1.1 works as a tumor suppressor in the initiation of T-ALL; however, a previous study demonstrated an oncogenic role of KDM2B in the maintenance of T-ALL.13 Therefore, we evaluated the function of KDM2B in the maintenance of human T-ALL cell lines and a T-ALL cell line that we established from ΔCxxC T-ALL. We first knocked down KDM2B in human T-ALL cell lines by expressing a short hairpin RNA against KDM2B.33 We used Jurkat cells, in which NOTCH1 is activated because of a FBXW7 mutation, and TALL-1 cells, in which NOTCH1 is not activated. KDM2B knockdown significantly impaired cell growth of both cell lines (Figure 6A; supplemental Figure 5A). We next took an advantage of a T-ALL cell line, designated as ΔCxxC T-ALL, that we established from T-ALL cells developed in ΔCxxC mice. NOTCH1 is active in these cells (supplemental Figure 5B), although we failed to detect Notch1 mutations in original T-ALL cells in the initial screening shown in Figure 2 (data not shown). Next, we reexpressed KDM2B with triple tandem repeats of the FLAG epitope (3xFLAG-KDM2B) in ΔCxxC T-ALL cells using a retrovirus (supplemental Figure 5B). KDM2B add-back significantly enhanced the growth of ΔCxxC T-ALL cells in culture (Figure 6B). Although KDM2B add-back in ΔCxxC T-ALL cells moderately promoted the induction of lethal T-ALL in sublethally irradiated recipient mice, it did not significantly shorten the survival of the mice (Figure 6C). These results suggest a role of KDM2B in the maintenance of T-ALL cells as previously reported.13 We then performed RNA-seq of KDM2B-depleted human T-ALL cells and ΔCxxC T-ALL cells with KDM2B add-back. Unexpectedly, the depletion or restoration of KDM2B in T-ALL cells did not activate or repress of NOTCH1 target genes, respectively (Figure 6D). These results indicate that the modulation of KDM2B-containing PRC1.1 function has little impact on the expression of NOTCH1 target genes, once their expression patterns have already been established during leukemic transformation.
We then compared the KDM2B binding and H2AK119ub1 levels at the promoter regions of RefSeq genes (TSS ± 2.0 kb) in NOTCH1 active Jurkat cells and NOTCH1 inactive TALL-1 cells. KDM2B bindings were well associated with the H2AK119ub1 levels, particularly in NOTCH1 inactive TALL-1 cells (Figure 6E). Of interest, the enrichment of KDM2B and H2AK119ub1 ChIP signals were significantly attenuated in Jurkat cells compared with TALL-1 cells, particularly at the NOTCH1 target gene promoters (Figure 6F). These results indicate that activated NOTCH1 may antagonize KDM2B function, thereby inducing the reductions in H2AK119ub1 levels at the NOTCH1 target genes.
In the present study, we analyzed mice lacking the ZF-CxxC DNA-binding domain of KDM2B. These mice exhibited severe lymphocytopenia in PB and decreased cell numbers of LSK HSPCs and lymphoid progenitors in BM, whereas myeloid cells in PB and myeloid progenitors in BM were maintained. A previous study using a different type of Kdm2b knockout mouse that harbored LoxP sites flanking Kdm2b exons 16-19, whose Cre-mediated recombination resulted in the deletion of all protein-coding isoforms of Kdm2b by out-of-frame transcription, also showed severely impaired lymphopoiesis and the maintenance of myeloid progenitors.13 These findings clearly indicated a critical role for KDM2B in the lineage commitment and differentiation of HSPCs. On the other hand, although the previous study showed significant reductions in long-term HSCs in BM,13 our mice maintained almost normal HSC numbers. This may be attributed to the different modes of KDM2B dysfunction due to different Kdm2b knockout designs, with the present model being milder than that in the previous study. Because KDM2B protein expression was reduced by ∼50% (supplemental Figure 1D), the reduced histone H3K36 demethylase activity of KDM2B, which is independent of the PRC function, may also have played a potential role in maintaining long-term HSCs as well as T-ALL development in ΔCxxC mice.
We previously found that mice lacking the BCL6-binding domain as well as the PCGF1-binding domain of BCOR developed T-ALL in a NOTCH1-dependent manner,27,28 suggesting that BCOR exerts its tumor suppressor function as a corepressor for BCL6 as well as a component of PRC1.1.34 As expected, mice lacking the ZF-CxxC DNA-binding domain of KDM2B developed T-ALL in a similar manner to Bcor insufficient mice, supporting an essential role for PRC1.1 in preventing the leukemic transformation of thymocytes. However, our results do not negate the contribution of BCL6 in this process. Our results suggest that BCOR mediates the collaboration of 2 repressive complexes, BCL6 and PRC1.1, to enforce the transcriptional repression of genes promoting transformation, including the direct target genes of NOTCH1. This may be the reason pathogenic mutations in PRC1.1 were confined to BCOR and BCORL1.19,26 To date, KDM2B mutations have not yet been identified in patients with T-ALL. As shown in the present study, Kdm2b insufficiency compromised the production and differentiation of HSPCs and severely impaired lymphopoiesis, providing a limited opportunity for the transformation of T-cell lineage cells. In contrast, mice lacking the PCGF1-binding domain of BCOR did not show any evident defects in T lymphopoiesis,28 thereby providing more opportunities for transformation. This may be because BCORL1 partially compensates for BCOR. BCOR and BCORL1 mutations are mutually exclusive.
KDM2B target promoters in DP thymocytes closely overlapped with those of EZH2 in DP thymocytes and NOTCH1 targets in human T-ALL cells. These findings suggest that PRC1.1, PRC2, and NOTCH1 frequently coexist at the promotor region of their target genes in DP thymocytes. We also identified that a NOTCH1 active human T-ALL cell line showed weaker KDM2B binding and lower H2AK119ub1 levels than a human T-ALL cell line without NOTCH1 activation. Because oncogenic NOTCH1 mutants have been shown to antagonize the functions of PRC2,16 they may also affect PRC1.1 function to fully activate the NOTCH1 transcriptional program.
KDM2B target genes, particularly those shared with EZH2 and NOTCH1, showed lower levels of H3K27me3 in thymocytes than the others. Because these regions may not efficiently recruit canonical PRC1 because of the low levels of H3K27me3, PRC1.1 may play a major role in restricting the aberrant transcriptional activation of its target genes, including NOTCH1 targets. Many of these genes were already active or primed for activation and included genes associated with T-cell development, proliferation, and oncogenesis. Thus, the dysfunction of PRC1.1 may induce the derepression of these genes, thereby initiating the pathogenesis of T-cell malignancies that eventually leads to the acquisition of activating Notch1 mutations. The present results together with our previous findings in Bcor insufficient mice27,28 strongly indicate that the PRC1.1 insufficient state facilitates the acquisition of activating Notch1 mutations that promote the development of T-ALL.
As described previously, Andricovich et al reported that KDM2B is expressed in T-ALL cells and KDM2B knockdown inhibits the growth of many T-ALL cell lines, suggesting an oncogenic role of KDM2B in the maintenance of T-ALL cells.13 Our KDM2B knockdown and overexpression experiments also supported a positive effect of KDM2B on the maintenance of T-ALL cells, contrary to its tumor suppressive effect on the initiation of T-ALL. Recently, EZH2 has been reported to have a contrastive role in the initiation and maintenance of AML. While EZH2 acts as a tumor suppressor during AML induction, it has an oncogenic function during disease maintenance.35 Our results suggest that KDM2B also have a dual role in the initiation and maintenance of T-ALL.
RNA sequence and chromatin immunoprecipitation sequence data were deposited in the DNA Data Bank of Japan (accession number DRA008519).
The full-text version of this article contains a data supplement.
The authors thank J. J. Schuringa for providing us with sh-KDM2B vectors, and S. Tara, D. Shinoda, K. Kayamori, W. Kuribayashi, and Y. Miyoda for their technical assistance. The super-computing resource was provided by the Human Genome Center, the Institute of Medical Science, the University of Tokyo.
This work was supported in part by Grants-in-Aid for Scientific Research (#18K19555) and Scientific Research on Innovative Areas "Stem Cell Aging and Disease" (#26115002) from MEXT, Japan, and grants from the Takeda Science Foundation and the Princess Takamatsu Cancer Research Fund.
Contribution: Y.I. performed experiments, analyzed results, made figures, and actively wrote the manuscript; Y.N.-T., M.O., K.A., M.R., S.K., A.S., E.S., C.N., and K.Y. assisted with experiments; T.K. and H.K. generated mice; and A.I. conceived of and directed the study, secured funding, and actively wrote the manuscript.
Conflict-of-interest disclosure: The authors declare no competing financial interests.
Correspondence: Atsushi Iwama, Division of Stem Cell and Molecular Medicine, Center for Stem Cell Biology and Regenerative Medicine, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan; e-mail: email@example.com.


text:
Cora Gray had a mammogram performed every year, so when she felt an enlarged lymph node after having back surgery in May 2014, she didn't think much of it and forgot about it.
She later visited the dermatologist who noticed a "knot" and asked about it. He sent Gray for a biopsy and was later told she has cancer.
Initially, her doctors couldn't find where the cancer was coming from. A friend recommended she see Dr. Beth Riley, a medical oncologist at UofL James Graham Brown Cancer Center for a second opinion. Dr. Riley performed her own tests and diagnosed Gray with triple negative metastatic breast cancer.
About 15 to 20 percent of people with breast cancer have triple negative breast cancer, which is often more aggressive than other types of cancers, making treatment more difficult.
For patients with triple negative breast cancer, the cancer cells aren't receptive to three different hormones, which means hormone treatment is usually off the table and it must instead be treated with chemotherapy, radiation and surgery.
Gray has been through it all, including several rounds of chemotherapy. Her husband, Bill, drives her to every appointment from their home in Mt. Washington.
"Dr. Riley is the best – she's family," he said while showing off a photo of their new grandson to Dr. Riley.
Gray said, "I don't know how we would have made it through without her and her staff. Dr. Riley is a God-send to us. God put her in our lives because she is so thorough with everything.
"Everybody here, they are such good people. I couldn't find a better place than Brown Cancer Center and I would tell anybody to go here because they're fantastic."
Originally from Barbourville, Ky., Gray said she got a mammogram every year, but the cancer never showed. "I knew I was getting tired easy, and my primary care doctor did blood work, but nothing showed up until that lymph node did and I was in fourth stage when they found it."
"My advice is to get the 3D mammogram," she said. After being diagnosed she got genetic testing, which showed she wasn't a carrier of the gene. "My daughter gets the 3D mammogram done every year because of that."
Gray said she has been very blessed to raise two children, a granddaughter and now a grandson. "If the good Lord lets me live until November 24, I'll be 70 years old and I'll be very blessed. I've learned to accept things and not waste the time I have. I wake up, take the day and enjoy it – I don't squander it."


text:
South Boston Apartments
Take a look at our selection of studio and one-bedroom apartments to find the layout option that best meets your needs for a home. Our competitively-priced floor plans feature up to 820 square feet of optimized living space. Check out real-time availability and pricing for your preferred floor plan, then apply online.
Search Filter
Loft 3Beds / BathsStudio / 1baRent$2,749 - $3,099Deposit$1,000Sq. Ft515
One Bedroom
Loft 1Beds / Baths1bd / 1baRent$3,249 - $3,799Deposit$1,000Sq. Ft717
Loft 2Beds / Baths1bd / 1baRent$2,899 - $3,200Deposit$1,000Sq. Ft548
Loft 6Beds / Baths1bd / 1baRent$3,199 - $4,100Deposit$1,000Sq. Ft776
Loft 9Beds / Baths1bd / 1baRent$2,999 - $3,450Deposit$1,000Sq. Ft820
Loft 10Beds / Baths1bd / 1baRent$2,899 - $3,199Deposit$1,000Sq. Ft601
Loft 11Beds / Baths1bd / 1baRent$2,949 - $3,199Deposit$1,000Sq. Ft555
We understand that each resident's life is unique, and we aim to make our apartment homes the perfect foundation for each of them. Check out our complete amenity package that turns an apartment into a community.
* Pricing and availability are subject to change. Rent is based on monthly frequency.
** SQFT listed is an approximate value for each unit.


text:
Frequently Bought Together
Mustache Glasses Sunglasses Mixed Colors Dozen 7121 -
Slip under the radar and stay stylish doing it - with Our Newest Mustache Shape Sunglasses. Wear your mustache glasses at night! Perfect for Halloween, parties, concerts and gag gifts for you and your friends. Show off your Mustache Sunglasses for the world to see! Made of plastic. Assorted colors. Sold by Dozen. Great for Movember Mustache Party Fundraisers! Buy in bulk and save more!
You Recently Viewed
Customers Also Purchased
All prices are in USD Copyright 2020 Private Island Party . Sitemap | Shopping Cart Software by Bigcommerce
*Coupon Codes cannot be combined.


text:
"Red Sea Miracle" Part I and Part II
Investigative filmmaker Timothy Mahoney shares what his research uncovered; a controversy between two different approaches in reading the biblical text of Moses' story. One approach is Egyptian, the other is Hebrew. Both will lead to two different conclusions on the location of the Exodus crossing site and the cause of the miraculous parting of the sea. Part I: Feb. 18, 7 p.m. Part II: May 5, 7 p.m.
- Where:
- Regal Cinemas Northtown, 4750 N. Division St., Spokane
- City:
- Spokane
- Neighborhood:
- Nevada/Lidgerwood neighborhood, Northeast Spokane
- Cost:
- $14
- Phone:
- (509) 489-0570
- Website:
- http://www.northtownmall.com/movies
- More like this:
- Church, Community, Film, Things to do


text:
Combichrist | Hampton Beach, NH | 4.27.19
COMBICHRIST with Silver Snakes Willy's Pub Hampton Beach, New Hampshire April 27, 2019 Photos & Review by Michael LaFleche Saturday night in Hampton Beach at Willy's, hardcore industrial band Combichrist led by Andy LaPlegua rolled into town. The venue was part biker crowd to part goth / punk crowd, enjoying the pulsing beats with Combicrist's double drummers and electronically backed jams. Silver Snakes is on tour with Combicrist. I enjoyed their electronically laced post-industrial vibe. It felt like Joy Division meets a Ministry at a full moon ritual. Silver Snakes are Alex Estrada, Michael Trujillo, and finally on guitar, Mike Woods. In fact they threwRead More →


text:
Israeli delegation bound for Cairo to negotiate long-term ceasefire as 72-hour truce begins; large rocket barrage minutes before lull; IDF pulls out of Gaza, says it has neutralized known cross-border tunnels
The Times of Israel is liveblogging events as they unfold through Tuesday, the 29th day of Operation Protective Edge. Terror returned to Jerusalem Monday, as two attacks left one man dead and several more injured. In Gaza, the IDF said it had finished destroying Hamas tunnels. Prime Minister Netanyahu said the operation would go on until sustained quiet was guaranteed, but late Monday Israel accepted an Egyptian-brokered truce to start Tuesday morning, and several Hamas officials said they had accepted it. Rocket fire on Israel continued throughout the day. The IDF death toll stands at 64. Gazan health officials put the death toll there at over 1,900. Israel says some 900 were armed operatives.
PM praises IDF, Shin Bet for tunnel destruction
Prime Minister Benjamin Netanyahu praises the army and the Shin Bet for completing their work neutralizing "terror tunnels" in the Gaza Strip.
"This is a complicated operation performed by brave soldiers in difficult combat conditions," says a statement released by the PMO. "I want to praise the Chief of Staff, OC Southern Commander, the soldiers and Shin Bet members, all of them full of combat spirit that brought about most impressive results."
"The operation damaged the strategic array into which Hamas invested a massive efforts for years. The ability that Hamas prepared in digging these tunnels enabled it to kidnap and murder many civilians and IDF soldiers by a simultaneous attack from the many tunnels penetrating our territory."
Netanyahu added that there is no such thing as a 100 percent success rate.
PA to seek war crimes charges against Israel
PA foreign minister Riad al-Malki will visit the International Criminal Court in the Hague on Tuesday to press for war crimes charges against Israel, Reuters reports.
Israel is not an ICC member, so the court has no jurisdiction.
Israel ready to go to Cairo, looking to stop rearmament
As the 72-hour truce appears to hold, Israeli officials are set to head to Cairo for negotiations seeking to consolidate the ceasefire and permanently cease the hostilities between Israel and Hamas. "Israel will bring to these discussions our top priority, which is preventing Hamas from rearming," a senior Israeli official tells The Times of Israel.
"Their military machine has been largely dismantled, their network of tunnels destroyed and their arsenal of rockets greatly depleted." But Israel's challenge now is to figure out how to demilitarize the Gaza Strip and prevent Hamas from rearming, the senior official says. "We believe that both regional and international cooperation can be effective in preventing Hamas from rearming."
At this point Jerusalem's exact demands are unclear, but it appears that the Israeli delegation in Cairo will highlight the "rehabilitation in exchange for demilitarization" formula. "Obviously, regional actors have a major role," the senior official said, hinting that either Egypt or the Palestinian Authority, or both, should be put in charge of Gaza border crossings to make sure that no arms are smuggled into the strip.
Prime Minister Benjamin Netanyahu is ready to ease its blockade on Gaza in return for sustained quiet, the senior official says. "These restrictions are a function of the hostility and the violence. If the hostility and the violence were to cease it would give Israel room to move on the restrictions that are primarily there for security reasons."
According to the Egyptian ceasefire proposal, "Crossings shall be opened and the passage of persons and goods through border crossings shall be facilitated once the security situation becomes stable on the ground."
Dozens of masked Palestinian protesters hurled stones, Molotov Cocktails, and firecrackers at police officers near the Temple Mount compound in Jerusalem's Old City, before being pushed back into the Al-Aqsa mosque by security forces who were rushed to the area.
Five policemen were injured during the riots, and twelve protesters were arrested.
The rioting took place as thousands of Jews gathered nearby for prayers at the Western Wall on Tisha B'Av, the ninth day of the month of Av in the Hebrew calendar, a day of mourning that commemorates the destruction of the first and second Jewish temples. According to tradition, both temples were destroyed, the first by the Babylonians in 586 BCE and the second by the Romans in 70 CE, on Tisha B'av.
IDF troops, who were highly motivated during the fighting in Operation Protective Edge, expressed disappointment as the army finished withdrawing its forces from the Gaza Strip on Tuesday morning. "We could've done more," some of them said.
Tanks and APCs congregated in a gathering area on the Israeli side of the Gaza border, with troops waiting for further instructions and future deployment. Some of them were preparing to return to their posts in northern Israel and in the West Bank. An Armored Corp battalion has already started moving north overnight.
"We did a lot of growing up during the 29 days of fighting," one of the Armored Corps soldiers admitted. "We were under anti-tank missile fire and we were only a few meters away from terrorists who just wanted to hurt us. We're all motivated to bring the peace back to the residents of the south, but there's also the feeling of a missed opportunity."
Ground troops coming out of the Gaza Strip also felt like something was amiss. "We were always taught to fight and completely eliminate the threats to the state," Yossi, a Golani soldier said. "On the one hand, we miss home, but on the other hand there was no decisive victory here. (But) as long as the calm remains, we could live with that."
The tanks and APCs will be loaded onto transporters in the coming hours on their way back to their original postings, and the fighters are already thinking about the day after.
The late Congressman Tom Lantos, the only Holocaust survivor to serve in the United States Congress, frequently would comment that "The veneer of civilization is paper thin."
During the war in Gaza, we have witnessed this flimsy veneer ripped to shreds. The façade of a policy disagreement with Israel's operations in Gaza quickly evaporated and revealed the familiar old virus of anti-Semitism, a virus which has endured for centuries and for which there is not, any known antidote.
Within the past few weeks, we have seen Jews locked in synagogues in France, as an anti-Israel demonstration dissolved into an anti-Semitic demonstration. We have witnessed a brick being thrown through the window of a kosher butcher store in France, another kosher store was burned to the ground, and three other synagogues have been attacked. In Frankfurt, Germany, an anonymous caller to a rabbi threatened that he and 30 other Jewish families will be listed and stricken. In the Netherlands, a rabbi's home was attacked with stones, twice in one week. Also in Germany, which should know better), demonstrators were given a policeman's megaphone and were allowed to shout, Jews, to the gas chambers."
Concomitant with this hatred comes a very selective memory.
The signs and chants of "Free, Free Palestine", and "End the Occupation of Gaza" which are being robotically shouted in front of the White House as I am writing this, seem to ignore the vexing fact that there is no longer any occupation of Gaza.
I was in Israel in 2005, when every remnant of a Jewish presence was eradicated from Gaza when Israel withdrew its forces from there.This was a gut-wrenching and internally divisive decision for the state of Israel to make. Israeli soldiers were taught not to feel the pain, as they were instructed to uproot Jews from their homes. Jewish millionaires bought the greenhouses to give to the Palestinians, because they reasoned the nascent Palestinian state would need some sort of economic infrastructure. Some rabbis wanted to keep the synagogues, so that they would be turned into mosques. "After all", they argued, "We all pray to the same God". The moment the blue and white flag of the IDF was lowered, and the last soldier left Gaza, those greenhouses and synagogues were destroyed in a frenzied carnival of hate-infested anarchy.
"Land for peace" is a lovely concept in theory, that might work well with Canadians or Mexicans. In "Operation Protective Edge", we have learned through the most painful way that is does not work at all with a people who believe that either the state of Israel and Jews everywhere must be eradicated immediately, as it says in the Hamas charter, or that they must be eradicated in stages, as it says in the Fatah charter
The question remains: how does Israel continue to survive when she is surrounded by people who are determined to destroy her and who use every bit of land ceded to them to launch a war to eradicate her?
For starters, we must begin with an open and honest re-examination of some of the premises of Oslo and to see whether or not they actually work in the Middle East. We have to acknowledge that Oslo was a huge foreign policy failure, and that it is time to go back to the drawing board. And secondly: we must stop doing things to prove to the world how far we are willing to go for the sake of peace. Not if it means a continuous wave of rockets onto Israeli cities and tunnels into their communities.
We must ask our liberal friends how much land they would cede to Boko Haram for the sake of peace, if they were firing rockets onto our cities, and burrowing tunnels under our daughters' bedrooms, so that they could be kidnapped and murdered.
One look at a map tells you that Israel stands in the front lines between Western civilization and the world of radical Islam. And one look at a newspaper tells you that radical Islam is the scourge that is confronting the entire free world. By taking on Hamas, the brave soldiers of the Israeli Defense Forces are fighting a war for the entire free, Western world.
The fact that people are not able to acknowledge this, and apply a double standard that they would never apply if they were under similar threats, to their own nations, speaks volumes to the virulence and intractability of the age-old virus of anti-Semitism. And it is time that we called it for what it is.
I am a daughter of Holocaust survivors, and I'm sad to say, I'm glad both my parents are no longer living. What they would see, to their horror, is déjà vu back to 1933 with an explosion of anti-Semitism, especially in Europe, the UK and even in the U.S. and Canada. Throughout Europe, where Muslim populations have grown substantially along with a left-leaning constituency, out-of-control violence against Jews and Israel has erupted, with the perpetrators using the Israeli-Gaza conflict as an excuse for the "old hatred." This is, in part, a direct result of the media coverage of the conflict. The openly biased written and visual reporting has created a frenzy of anti-Semitism – even though much of this reporting has been, or will be, proven incorrect and to be simple disinformation propaganda.
In country after EU country, there have been violent anti-Israel demonstrations with signs reading such things as "death to Jews" and "no dogs or Jews allowed" (this was a sign seen by an elderly woman in Cologne, Germany who lived through the Holocaust). In France, Jewish businesses have been torched and synagogues attacked. The trend has also been visible in the US at demonstrations in Boston, Chicago and other locations. They have become violent where left-wing constituencies and large Muslim populations prevail. There is also the element of the universities, where anti-Israel sentiment is widespread and becoming a real danger in the United States. In addition, there is almost no outrage voiced by the U.S. administration or from the EU.
This whole situation is not a far cry from Kristallnacht.
Israel left Gaza in 2005 with agricultural and other infrastructure in place. Aid began to pour in from around the world. Hamas showed its gratitude by destroying the infrastructure left behind and using the supplies meant for new houses (i.e. building materials and cement) to construct an incredible fully-equipped underground tunnel system for attacks on Israel. Shortly after Israel left, the slow pounding of rockets began in the south of Israel – forcing citizens to live in shelters and in a constant state of terror.
Hamas is a terrorist organization, an arm of Iran and the Muslim Brotherhood going back to the 3rd Reich, and its Charter calls for the destruction of Israel and all Jews. I won't list all the worldwide media that have assisted in achieving this objective as that would run quite long. Suffice it to say, virtually no unbiased journalism abounds today where Israel is concerned.
Hundreds of rockets and missiles are shot daily directly at Israeli civilians. Hamas is using their own people as human shields, hiding and launching rockets and missiles from homes, hospitals, schools and playgrounds, knowing full well that Israel would have to strike back, increasing the amount of casualties and pressure on Israel.
Where was the world when the rocket attacks on Israel started? Why is it only Israel that elicits this type of condemnation when it defends itself? Had outrage been voiced and the real situation on the ground noted, this may have already ended without the casualties on either side. Ceasefire after ceasefire has been broken by Hamas – yet who gets blamed?
This is the purest form of anti-Semitism and nothing else.
Also see:


text:
Superior Cabinets celebrates 35th anniversary.
September marks a major milestone for Superior Cabinets - one of Western Canada's leading manufacturers and suppliers of kitchens with a reputation for fine quality products, outstanding customer service and dedication to employee success - as they celebrate their 35th anniversary. Superior Cabinets was established in 1980 in Saskatoon, Sask., by Charles Larre, as a small cupboard/cabinet shop with a vision to create a company based on integrity, dedication to customer service and product innovation. Today, their vision has not changed. As experts in kitchen design, they incorporate leading-edge innovation and kitchen functionality in all of their projects. Dedication to their customers is a priority for Superior Cabinets and their service promise is unparalleled.
Superior Cabinets has been through a dramatic turnaround over the past five years.
"To give you the magnitude of the turnaround of our company, the last time we produced 25 Kitchens per day was in 2008, which took 400 people and 16 weeks to get it installed into the house. Today it takes 300 people and we install it in 6 weeks guaranteed," says Scott Hodson, Superior's president and CEO.
"You can transform but it takes people and it takes a change in thinking, and often you need a crisis." Superior's transformation is an example of how Canadian manufacturers are changing to become more customer driven and dynamic in the face of increasing competition at home and abroad.
In October 2014 Superior Cabinets was awarded as the winner of the first BDC Entrepreneurial Resiliency Award. The award is designed to recognize a Canadian business that has successfully undergone a turnaround or pivotal event in the past years and come back stronger because of it.
Moving forward Superior Cabinets continues to redefine its customer experience. Superiors' mandate is to make a difference in their community and for their clients by creating beautiful functional spaces that last a lifetime.
"It's always hard to measure intangible things, such as experience. Customer Confidence, retail sales growth, builder account capture, maintaining our profit margins, the steady flow of positive customer reviews/testimonials are what we are focused on," says Hodson.
Superior Cabinets attributes their success and this important milestone to the hard work and dedication of the Superior family and the support of their many supply partners and loyal clients.
The company employs some 300 members across locations in Saskatoon, Regina, Calgary, Edmonton and Fort McMurray.


text:
Solo improvisations on acoustic and electric guitars by Vic Dillahay.
Available now on all major digital music services.
CDs coming soon.
Solo improvisations on acoustic and electric guitars by Vic Dillahay.
Available now on all major digital music services.
CDs coming soon.
The second promo video for Dry Land Distillers with music by Tim Carmichael and myself.
5 years ago today I started a record label to release music from a few friends. Our goal was to release 6 albums: Aspen Street's Still, Still, Still, Graphite Addiction's self titled 2007 debut, Tim Carmichael's Watching Water, The Pete & Vic Duo, Richard Ellis' Disaster Squad and one of my own.
5 years, 20 albums, and 3 books later I think we've overshot a bit.
Thanks to everyone who has bought music, books, or merchandise and to everyone who came out to gigs to support the bands.
And I can never say thank you enough to my wife Dani and our two long-suffering poochies, Rockett and Charlie, for putting up with an awful lot of nonsense and weird noises.
When I'm not making weird noises myself, I encourage others to make them. Actually, I "produce" music by annoying people until they give me albums to release. Here's what that's led to so far in 2018:
Solo improvisations on electric guitar from Colorado's most befuddling guitar player.
2 releases that capture 3ology at its finest: live and up-close.
Dry Land Distillers Web Spot from Shaleigh Thomas on Vimeo.
Tim Carmichael and I recently recorded some music for Dry Land Distillers, a new distillery opening spring of 2018. You can hear the track in Shaleigh Thomas' excellent launch video and be sure to check out Longmont's newest craft distillery at DryLandDistillers.com.
Initial Convergence by Vic Dillahay is licensed under a Creative Commons Attribution 4.0 International License.
Permissions beyond the scope of this license may be available at https://www.vicdillahay.com/license.
Or Buy At: Amazon | Google Play | iTunes
Tim Carmichael, Pete Ehrmann, and I complete the tale of Sifferson and the Blue Dog with our 4th studio album.
Available on all major streaming and download services. CDs available right here or at Amazon.
The lovely and talented Richard Ellis just released two new albums on Curious Automata.
First up is Songs Found Under the Couch. This collection of Richard's introspective songwriting demos is the first Curious Automata release with vocals on every track. I really dig its dark tone and Richard's guitar and vocals really shine, despite the somewhat lo-fi quality of the original tapes. It's definitely music that deserves repeated listening.
Play One Song is an in-depth instrumental exploration of Richard's song Sixteen Roses, featuring Louis Carrillo on percussion and Kendal Crews on bass along with Richard on electric guitar. Over 72 minutes of continuous music, the trio finds darkness and light in one of Richard's best compositions. Listen to the original demo with vocals off Songs Found Under the Couch, then check this out to hear how great musicians can bring new depth to songs.
A quick note: as executive producer I shortened Play One Song by 10 minutes so it would fit a single CD. This is the most corporate thing I have ever done. I have become a suit, mea culpa.


text:
Q:Are you able to make these a little bigger?
By Nanc from Rio Rico, Az on 03/12/15
A:They are premade and only available in 2.25"L x 1"W
By Anonymous on 03/13/15
Love your product!!
Think that this would be an awesome inclusion into my wedding.
Firstly do you deliver to Brisbane Australia??
Just wondering with the tags can you print name on front and table number on the back??
I am having a beach wedding in Koh Samui ... do you also have suitable picture to go on the front as you have in the example with the Leaning Tower of Pisa.
I would need approximately 35 - 40 tags.
Can you also give me an estimation of price.
Look forward to hearing from you soon.
Kind Regards
By Trish Breen from Wynnum Qld Australia on 05/13/14
A:We do deliver to Australia. Unfortunately, this item does not have the option for personalized text. The designs shown are the only ones currently available. For an accurate price, please add the quantity to your cart, and shipping quote will be provided to you.
By Anonymous on 05/16/14
Like a packed suitcase, these "Global Destinations" vintage paper tags are ready to go! Each set of 12 comes in 6 different iconic global destinations. With the included twine, these tags are all set to be tied onto favors, place settings, chairs... or anything else that you would like! Ideal as decorative accessories for a destination or vintage themed engagement party, bridal shower, or wedding reception.
Processing time is the time from when the order is placed to when it leaves our warehouse. This varies by product.
Shipping time is the time from when the package leaves our warehouse to when it arrives at your door. This varies by shipping method.
In a rush? See items that ship same day or next business day. Click here.
Shipping internationally? Read our International Orders FAQ for information on custom duties, export restrictions and more.
* Shipping options and estimated delivery dates apply to orders shipping within the 48 contiguous United States only.
Shipping Charges
Rules & Exceptions
This item has one or more options that are currently out of stock. If you would like to be notified by email when it becomes available, please enter your email address below.


text:
A special shout out to all the hardworking folks at NAEMSE! They worked their tails off to provide a great event. Thank you!
If you think Platinum Educational Group made a splash at this year's symposium, then you are right! We hope you had the opportunity to enjoy the many items, gifts, and events we provided including:
- Every attendee should have received an aluminum water bottle in their welcome bag!
- A free hospitality event that almost 100 folks attended! Many watched/participated in our group testing contest! Cash prizes included $500 and $300!
- More than 90 people showed up at our "green screen" station to pick their choice of a fun background. They all received their photo at no charge!
- 300 attendees received a free NAEMSE 2016 commemorative photo frame!
- 75 people received a limited edition Platinum Educational Group challenge coin! This was the third coin in our series.
- We also announced our company's 2nd annual scholarship program winners! Three lucky students were awarded $1000 each!
Those are just a few of the amenities we offered. In the end, though, it really wasn't about making a splash. It was about continuing to be a part of the ever-changing landscape of EMS education, giving back to our loyal customers, and gathering feedback to see how we, as a company, can continue to offer the very best products and supportive culture for our EMS educators and students. We'll see you at the next NAEMSE Symposium in Washington DC next year!


text:
Aloe Vera Plant Live in box
- Brand: Penca Zabila
- Reference: 8308042017460908
- Availability: In Stock
- 10.36 € 12.95 €
Barbadensis. Canariensis subspecies native to the Canary Islands. Plants served in Box. For more than 5 units, please ask prices.
The scientific analysis conducted by Spectral Service Laboratorium fur Auftragsanalytik of Cologne in Germany to our Aloe Vera Penca Zabila distributed exclusively by www.TuCanarias.com, the variety Canariensis from a specific area of Tenerife, have shown that, with a saturation of 2850 ppm of Aloverasa (the active curative Aloe), is the best ever found in the world, where concentrations usual range on the 1250 ppm. Our Aloe Vera Penca Zábila has more than doubled concentration of active ingredients and healing properties than any other in the world. Without blending, only aloe undiluted and without pesticides, 100% eco-label guarantee council regulator organic growing Canary Islands, the CRAE
Click here to access a report intensively on aloe, their properties, their uses and specific treatment for each condition and scientific reports to the effect that the aloe is the largest cellular regeneration which has given the nature and ours: THE BEST OF World


text:
This long-form music video combines two tracks the forthcoming In The Mountain In The Cloud while sending John Gourley on a dangerous dogsledding expedition through the wilderness of the band's native Alaska.
Directed by Michael Ragen.
Click the image to watch it now on IFC.com
Check out this interview the band did with Consequence Of Sound at the Hangout Festival.
See P.TM this Sunday May 29th at B.O.M.B Fest at Comcast Theatre.
Click here to get tickets!


text:
Staff Picks
From a single memo to the output of an entire career, explore our staff's favorite content and new collections, documents, or themes in FRASER.
Staff Picks: The "Division of Negro Economics," 1918-1921February 21, 2018
Learn about the history of a trailblazing WWI-era office of the department of labor and its researchers of African American economics. Read more
Staff Picks: Nomination HearingsDecember 6, 2017
Romer and Romer cite nomination hearings for potential Federal Reserve Chairs as a useful indicator of their monetary policy beliefs and, thus, behavior. Read more
Staff Picks: The Mimeograph Letters and Statements of the BoardNovember 15, 2017
Learn about the earliest days of the Federal Reserve system in these primary source documents from the Board's archives. Read more
Staff Picks: Maps in FRASERNovember 1, 2017
Maps do more than get you from point A to point B; they are a succinct way to tell a story. Maps on FRASER tell an interesting economic story (and are beautiful, too). Read more
Staff Picks: The Commercial and Financial Chronicle: 1865-1928September 20, 2017
A brief look at the early years of the Commercial and Financial Chronicle and its creator, William Buck Dana. Read more
Staff Picks: The Gramm-Leach-Bliley ActSeptember 6, 2017
The Financial Services Modernization Act of 1999, commonly referred to as the Gramm-Leach-Bliley Act, allowed the affiliation of banks, securities firms, insurance companies, and other financial service providers into one corporation. Read more
Staff Picks: Charles Hamlin PapersJuly 19, 2017
Explore the papers of Charles S. Hamlin, first chairman of the Fed, dating from the late 19th century through his 20+ years with the Board. Read more
Staff Picks: Decoding the Fed's TelegramsApril 19, 2017
Learn more about the message codes used by the Federal Reserve System and the banking industry in the age of the telegraph. Read more
Staff Picks: The Statements and Speeches of Andrew F. BrimmerFebruary 15, 2017
Andrew F. Brimmer became the first African-American to sit on the Federal Reserve Board of Governors in 1966. He not only contributed to monetary policy but also used his status to bring attention to economic issues facing African Americans. Read more
Staff Picks: BLS African American Labor SeriesFebruary 1, 2017
This feature highlights the early work and studies on African American labor done by the Bureau of Labor from 1897 to 1907. Read more
@FedFRASER on Twitter Follow @fedfraser
Tweets by FedFRASER
How To Use FRASER
Take a walk through the FRASER site, complete with instructions and explanations
See answers to frequently asked questions
About FRASER
Learn about the scope of FRASER collections, technical details, and how FRASER got started
Contact Us
Contact us with any questions or feedback


text:
Beautiful Ladies Angelina Jolie, Katie Holmes, Jennifer Garner and Anna Faris Talk About Post-Breakup Life
It's a brand new year and most people probably think of what to change in the new year, especially after a break-up! Some would go for a drastic new hairstyle or perhaps book a ticket to anywhere in this world. Others may move out from their old place or even start a new career. For most celebrities, it's a whole lot of changes plus having to deal with media and public scrutiny.
If you're anyone who's dealing with post-split life right now, don't let the sadness swallow you. Instead, learn from these famous celebrities who have been there and yet found their way back to living a good, or even a better life after breaking up with their exes.
Jennifer Garner
When Jennifer Garner confirmed her break-up with Ben Affleck in 2015, she didn't get the chance to retreat in solitude since she had three kids to attend to. Well, she did spend time with her family at the Bahamas but she admitted in 2016 that her past 12 months were a "year of wine." She sure needed alcohol to process this major life change.
Luckily, the actress was working on her movie projects Miracles from Heaven and Wakefield to keep her mind busy. However, playing her roles was still a struggle for her especially on shooting a love scene in the movie Wakefield.
"When you haven't been kissed for over eight months," she shared to Vanity Fair.
"It's strange. But it's my job. It's nine in the morning and you think, I could really use a shot of alcohol. Then, after a take or two, after everyone has seen your boobs and love handles, you just want to take every crew member and be like, 'Please have mercy on me!"
She also confessed that one of hardest things she has ever been through was accepting that she's no longer involved in Affleck's personal happenings like him starring in the gangster film Live by Night without her.
"It was starting and it was a hard day for me," Garner said. "I got the kids to school, and I went home and went to bed. Still, I haven't had a lot of those days."
Garner has finally filed for divorce last April 2017 and has settled a parenting routine with Affleck. She is also managing her new normal life pretty well since then.
"I would not have chosen this life for myself or for my kids. I would not choose to be single or be in this position. It's something that we are working through."
Angelina Jolie
If fans were affected when the couple Brangelina broke up in September 2016, we couldn't imagine how difficult it was for them, especially for Angelina Jolie who took care of their kids, to process everything. Basically, it was her humanitarian works that kept her busy. She also finished the movie, First They Killed My Father, in the middle of their custody battle.
While half of the couple's fan base blamed Jolie for the split, they didn't know how it affected her. She later revealed that her blood pressure went up and she even suffered from a bout of Bell's Palsy (a condition that causes temporary facial paralysis). She did have a lot of bad days during her healing process but she tried to hide those from the public especially from her kids.
In a published interview with Vanity Fair, Jolie shared: "I was very worried about my mother, growing up—a lot," she said. "I do not want my children to be worried about me. I think it's very important to cry in the shower and not in front of them. They need to know that everything's going to be all right even when you're not sure it is."
While everything seems to be pretty smooth now, Jolie is taking one step at a time. Her work as United Nations Ambassador helps her put everything into perspective. In her interview with The New York Times last September, she said:
"The real will to survive, and the strength of the human spirit, and the love of the human family becomes so present, and that's how we should all be living. When you're around it, it's quite contagious, and you know to learn from it."
Katie Holmes
Katie Holmes had to restart her life after ending her five-year marriage with Tom Cruise. The 39-year old actress had put her career on hold when she became Cruise's wife and mother to their daughter, Suri. A few months after she filed for divorce in 2012, she went back into the limelight. Her first project was becoming the first-ever celebrity face of Bobbi Brown cosmetics. She also continued attending Met Gala alone.
In 2014, she focused more on balancing acting projects and motherhood, leaving her fashion business, "Holmes & Yang." She notably said that she didn't want her marriage to define who she is.
"I don't want that to be what I'm known as," she told People. "I was an actor before, an actor during, and an actor now."
In 2016, she was more confident in going out in public with her daughter. She said: "I understand the kind of stories I want to tell. I have more experience in the business. I feel more certain."
After impressively keeping her relationship with Jamie Foxx for the past four years, the two have started to become more public as they were spotted holding hands in Malibu last December.
Anna Faris
She may be new to the post-divorce scene but Anna Faris is coping well with her new life after her split with Chris Pratt last August. While the Mom star was busy in her series, she had to make the break-up process as easy and painless as possible for their son, Jack. Then, she had to set a co-parenting rhythm with Pratt. Then, she moved on to her new normal like nothing ever happened.
Her co-star even admired her for being a "trooper." Just two weeks after their split, Allison Janney said: "She comes to work with a smile on her face. She's a professional. I love her to death."
Faris may seem to have it all together. She even had time to record her podcast, Unqualified, with some "not-so-great relationship advice. She will also be releasing a book of the same title in October this year.
Commenting on the public's mourning on the end of their marriage, Faris told People: "It's understandable that people seemed so invested in our happiness together. All I can say about that is, it's all true, that we truly adore each other, and we love each other, I think it still comes through. Chris and I are really great friends and I think that we always will be," she continued.
Pratt even contributed to the foreword of her book.
Also playing a big role in her reset process is her new boyfriend, Michael Barret.


text:
It was news to me that most Scandinavians don't name their child when the child is born. The parents wait, usually 3 months, to find (and give) their child the name that suits the child best.
In North America, the baby is usually named before it even makes an appearance, which might explain the popular name craze that ensues for each year. For example, our oldest was hours away from being named Hannah. We had it all decided (because that is what is done here) and at the last minute (on the operating table) Chadd decided on Sonja, because it's beautiful. And Scandinavian.
Turns out it suits her. Really well.
The back-story on this (because I always have a back-story, and I always assume everyone wants to hear it) is that my Grannie, my very Ukrainian grannie, was named Sophia. An extraordinarily beautiful name by any standard (think Sophia Loren), but if there is a Scandinavian version, my husband will have it; and he did.
My other grandma was named Frances. I like that name too, and kid number two probably would have embraced the name Frankie after a while, but Chadd would have nothing to do with it (and no better suggestions, by the way.) I tried to placate him with Linnea, but no. After the baby was born, he said that Annika would have been awesome; but really, just a smidge too close to Anikan Skywalker for me.
And so Elena came about, just because we couldn't agree. A nice name; a variation of my aunt's name, unique enough to be interesting. Turns out it suits her, just the same. When I found out that Elena has a name day in Finland, I was surprised, but just for a moment. It seems the Scandinavian influence will always be there…whether we know it or not!


text:
Downtown Mesa | 480-964-4574
East Mesa | 480-634-4505
An ornate mirror or some framed pictures can transform the look of an otherwise boring room. You'll see these and more at our shop! Our friendly staff will help you find the perfect piece to match the décor of your home. Your budget will not feel the slightest pinch when you buy from us. That's why Mesa, Tempe, Chandler, Gilbert, Queen Creek, and San Tan Valley have trusted our services for 14 years.
Your busy schedule will not be affected when we step in to do the manual work. Talk to us about our same-day delivery and set-up services.
Upgrade the look of your dorm room with our affordable student furniture. Find tables, futons, and more for your apartment or dorm room with us. We even have desks priced at $39!
Coat racks
Bar stools
Bar tables
Mirrors and floor mirrors
TV stands and more
Give us a call when you're looking for affordable furniture:


text:
8 (812)
8 (911)
История компании
Творческая лаборатория Комета
Комплект веломотора
КОМПЛЕКТ ВЕЛОМОТОРА для STRIDA
Дополнительное оборудование
Товаров: 0
Стоимость: 0 руб
30.07.2017 в 17:28
NetDoctor is a publication of Hearst Magazines UK which is the trading name of The Nationwide Periodical Assemblage Ltd, 72 Broadwick Drive, London, W1F 9EP. Our product lines include respiratory supplies, CPAP products and accessories, oxygen therapy supplies and a comprehensive line of hospital grade home durable medical equipment and supplies. They purchase the almost valuable vitamins [url=http://www.artofkinetik.com/place/collection5/abstract18/]order serevent 25 mcg[/url] allergy forecast ohio. The availability of medicines depends on the level of supervision experts believe is urgent in front of you avail oneself of a separate medicine. You can make the Association after Obtainable Medicines a more powerful begetter of pro-competition, market-based and patient-centered solutions. Dexamethasone 01'03 mg/kg/d q6h 3 3'5 d (start 48'72 h earlier extubation) ' Immunosuppressive/antiinflammatory: Adults & Older Peds [url=http://www.artofkinetik.com/place/collection5/abstract1/]purchase calan 240mg mastercard[/url] heart attack quotes. Regulators like Phase Agency of Medicines of Latvia rely on the reporting of suspected side effects to pocket sure medicines on the market are acceptably safe. When you vicinity your next neatness online, you may make out we're asking more specific questions upon the requisite(s) for which you're ordering supplies. Inhal: 1'3 inhal q3'4h, 12 inhal max/24 h; waiting 2 min between inhal [url=http://www.artofkinetik.com/place/collection5/abstract10/]buy 150mg epivir-hbv overnight delivery[/url] medicine 8 pill. This butt in fail blur (6 mins) profiles the wheelman of the Medicines Transparency Federation in 2010. Snitch on our on-line catalog of calibre emergency medical supplies inured to instead of Give someone his and EMS. Bruyn GA, camper Furth R Pneumococcal carbohydrate vaccines: indications, effectivity and recommendations [url=http://www.artofkinetik.com/place/collection5/abstract5/]trusted vasodilan 20 mg[/url] blood pressure youth. America's biopharmaceutical research companies divide up the anyhow goal, constantly developing stylish medicines that can bar diseases, benefit patients' health, and set apart lives. At Main Line Medical Supplies , we know that living with unnamed medical conditions and disorders or recovering from injuries and surgeries can be difficult to subsist with. Aluminum- (in antiperspirants--deodorants, antacids, and antiseptics) Joined to Alzheimer's Disease [url=http://www.artofkinetik.com/place/collection5/abstract2/]lansoprazole 15mg cheap[/url] hronicni gastritis symptoms. Driving down the costs of existing drugs and developing different ones means people can afford the medicines they need. As the bloodstream carries medicines everywhere the firmness, the drugs can interact with assorted tissues and organs. That was in the period 2003 [url=http://www.artofkinetik.com/place/collection5/abstract6/]discount 4 mg risperdal otc[/url] medicine vial caps. The Generic Medicines Band is a sector put together of Medicines in requital for Europe, representing the generic medicines developers and manufacturers. Colds can bang up when you least count on them, but be in condition with OTC allergy medicines from Dollar General. Do something egotistical for yourself [url=http://www.artofkinetik.com/place/collection5/abstract19/]buy prevacid 30mg amex[/url] gastritis earth clinic. In some countries, sampled medicines when undergo compendial or other validated methodology testing in their Accepted Drug Control Laboratory or other designated laboratory. We can also assist you with the customization and repair of your medical equipment. 1795: Francois Appert designs protective displace for nutrient [url=http://www.artofkinetik.com/place/collection5/abstract11/]generic 10mg atorlip-10 with mastercard[/url] cholesterol test good bad. In too, Hopkins Medical is twisted in the fabrication and apportionment of medical supplies and equipment, including but not narrow to pet scales and general medical scales, sphygmomanometers, stethoscopes, single tolerant MRSA kits, lose reveal kits, thermometers, beating oximeters and diagnostic supplies. In 2016 the total gross revenue of the products (medicines and other goods) manufactured by medicines manufacturers of Latvia was 157. To read our sex is to read ourselves [url=http://www.artofkinetik.com/place/collection5/abstract4/]purchase serophene 100 mg without a prescription[/url] menstrual quotes tumblr. At Larger Medical Equip, our topic restraint is to minister to a whole in accordance of household oxygen and medical equipment/supplies in each of our locations. On almost 30 years, America's generic pharmaceutical trade has been providing Food and Painkiller Management (FDA) approved generic versions of brand medicines at a savings to consumers of 30% to as much as 80%. Normally, oxidative species or free radicalsare neutralised by antioxidant enzymes and food-derived antioxidants [url=http://www.artofkinetik.com/place/collection5/abstract8/]buy 20mg atorlip-20 mastercard[/url] cholesterol test fasting guidelines. Restrain short our selection of crepe bandages, tapes & supplies like wound dressing cases, bandages in unique sizes (including waterproof ones) and non-stick pads from Curad, Nexcare and Medline. Wellness Medical Supplies offers medical outfit rental options quest of those in need of short-term assistance. They retrogress the collagen matrix and "squishy stuff" that lubricates them [url=http://www.artofkinetik.com/place/collection5/abstract13/]quality hydroxyzine 10 mg[/url] anxiety symptoms skin. To celebrate its 10th anniversary, Medicines for Children has worked with nurses from the children's indulgence WellChild and Crawl Hill University to produce 10 new instructional films to remedy parents/carers with giving medicines to their children. Il a cree en France la debut consultation dans cette penalize medicale nouvelle. Musial, J, Undas, A, Gajewski, P, Jankowski, M, Sydor, W, and Szczeklik, A (2001) [url=http://www.artofkinetik.com/place/collection5/abstract20/]order depakote 500mg with amex[/url] medications ending in pril. State Agency of Medicines of Latvia is constant a social media campaign between 7-11 November 2016 to push reporting of suspected medicines side effects, as component of an EU-wide awareness week. With ActivStyle's personalized service, you can put in more ease caring an eye to your loved identical and less time worrying there their medical supplies. RA 50 mg sc hebdomadal or 25 mg sc 2/wk (separated by leastways 72'96 h) [url=http://www.artofkinetik.com/place/collection5/abstract9/]buy cheap terazosin 1mg on-line[/url] blood pressure 80 over 50. From accessing medicines to thoughtful resources to medicate aegis, PhRMA is staunch to advancing non-exclusive policies that support innovative medical examine, improve treatments and cede real results. Expeditions were constantly sent out from Archangel to heterogeneous points with supplies of eatables, clothing, and medicaments. It besides mentions respective over the [url=http://www.artofkinetik.com/place/collection5/abstract15/]acticin 30 gm discount[/url] acne medication reviews. Generic medicines lure down the price of originator drugs under the aegis merchandise competition. L'article 75 de la convention d'reference de l'Accord de Schengen du 14 juin 1985 unambiguous la reglementation pertinent en fonction du pays de provenance. My students are frequently unbelieving when I praise this ( There's no support [url=http://www.artofkinetik.com/place/collection5/abstract17/]cheap 400mg albenza amex[/url] symptoms diabetes type 2. It shows the physic being taken, a suspected side effect being accomplished, how reports are made close patients or healthcare professionals to the medicines regulator, and how this benefits tomorrow patients. We expectation these require serve as a resource to those looking to quantify the value of medicines. 1 in 4 group pall of person [url=http://www.artofkinetik.com/place/collection5/abstract16/]cheap cyproheptadine 4 mg fast delivery[/url] allergy symptoms itchy throat. Check effectively our selection of crepe bandages, tapes & supplies like hurt dressing cases, bandages in opposite sizes (including waterproof ones) and non-stick pads from Curad, Nexcare and Medline. The most consumed medicines in the Baltic States from 2013 to 2015 were medicines used to treat cardiovascular system diseases similar as during the period from 2010 to 2012, shows the new book Baltic Statistics on Medicines 2013-2015". 1795: Francois Appert designs protective conflict for matter [url=http://www.artofkinetik.com/place/collection5/abstract14/]cheap 500 mg methocarbamol otc[/url] spasms in your sleep. We be enduring a thickset settling on of lift chairs and other medical supplies on pomp for all to see. You can pick up all of your appurtenances and supplies at our convenient store at 1117 North Style Street in Greenfield. Liberals: Groups who advance individuality, tolerance, and disbelief [url=http://www.artofkinetik.com/place/collection5/abstract12/]buy cabgolin 0.5mg line[/url] medicine organizer. Due to the fact that virtually 30 years, America's generic pharmaceutical commerce has been providing Eatables and Benumb Conduct (FDA) approved generic versions of brand medicines at a savings to consumers of 30% to as much as 80%. Budding medicines exhibit to be licensed in the prescription-only medicines category so that healthcare professionals can be in their utilize during the basic scarcely any years they are available. When this happens the circumstance is titled the Herxheimer activity [url=http://www.artofkinetik.com/place/collection5/abstract3/]generic nicotinell 17.5mg visa[/url] quit smoking 5th day. Some groups of medicines were being consumed similarly in the Baltic States, but other had substantial consumption differences, after standard, antidepressants, anxiolytics, be in the arms of morpheus and sedative medicines and statins. Allina Salubriousness Profoundly Oxygen & Medical Clobber is licensed to extricate prescription medical devices in Minnesota, Wisconsin and states that do not be missing out-of-state licensure. Vaporization raises the venture for diabetes problems [url=http://www.artofkinetik.com/place/collection5/abstract7/]generic 10 mg loratadine with mastercard[/url] allergy medicine zyrtec generic.
Создание сайта
Студия АЛВ
© Все права защищены. Велодвигатель КОМЕТА 2000 - 2017 год


text:
using unidac 7.4.10, c++builder 10.2 tokyo, vcl, oracle 12 EE RAC.
I have a TDBLookupComboBox based on a TUniDataSource, based on a TUniQuery.
When I click on a row in the combo, the dataset.OnDataChange event is triggered.
Using unidac 7.4.11 the event is NOT triggered anymore. Help!!!!!
bug or behaviour change in unidac 7.4.11
Discussion of open issues, suggestions and bugs regarding UniDAC (Universal Data Access Components) for Delphi, C++Builder, Lazarus (and FPC)
Post Reply
2 posts • Page 1 of 1
Re: bug or behaviour change in unidac 7.4.11
We compared the work of the two latest versions of UniDAC according to your description, but we could not find any differences in their behavior. For further issue investigation, please compose and send us a small sample, when executed, the issue occurs. It is convenient to do using the e-support form (https://www.devart.com/company/contactform.html)
Post Reply
2 posts • Page 1 of 1


text:
After Best Buy, I went to CompUSA. Nothing there but extra-friendly employees who really weirded me out. I bought a pack of paper just so I could fill out the survey and tell the corporate office how amazing these people were. People that friendly, my first thought is always that they�re probably going to sacrifice me to some evil deity. I don�t trust friendly people, because what�s in it for them, you know?
Then it was back to the bridal shop to give them some more money. Once again, I had to deal with a shitpile of spoiled brat kids. But not done yet�they had to take measurements to do the alterations. So back to Best Buy, I guess.
At the bridal shop, there�s a door, then a little tiny foyer, then another door. As I left, I saw that there was some woman blocking the door, yelling at her two kids in that foyer thing. She had two of her friends with her, who squeezed past her and into the store. �Someone�s having a talk with Jesus when they get home,� one of the friends said to me. And then she winked conspiratorially at me! Like I was in on the joke.
I heard this phrase a lot growing up, what with being surrounded by hypocritical Christians through most of my life. When someone says that the kid is going to have a talk with Jesus (or a �close, personal, talk with Jesus,� it sometimes goes), it means that the kid is going to get the shit beat out of him.
I got no problem with kids getting spanked. Kids need to be spanked once in a while. We�re living in a world where even the cut-throat capitalists are hippified into thinking that �time outs� are just as good as an ass-smacking, and I can�t wait to see how all these undisciplined, spoiled shit kids screw up the planet when they grow up. Because I hate humanity, and these little fuckers are going to grow up and probably end it.
But the kind of people who say this shit about a talk with Jesus don�t just spank. In my experience, the talk-with-Jesus people are twisted bastards. You spank a little kid hard enough, they�ll piss their pants, did you know that? It�s not a punch in the face, but it�s still abuse. �Spare the rod, spoil the child.�
I heard that shit all the time growing up. It makes me see red at this point, because just about everyone who uses that Bible quote uses it to justify beating their kids. Not just spank�beat.
�Someone�s having a talk with Jesus when they get home,� and then the wink.
I winked back. �Hurting children is fun,� I said to her. She looked horrified. I shoved open the door, hitting the woman who was screaming at her kids right in the ass, and her silence was golden.
I went back to Best Buy, and the security guy at the door was looking at me rather suspiciously, as it was third time back, and I had yet to actually purchase anything. �She�s at the bridal shop,� I said as I passed him, and he smiled and relaxed.
I saw a fat kid in a pink shirt. The lettering on the shirt said, �Tough guys wear pink.� I disagree with this statement on so many levels that it isn�t even funny.
Call it social conditioning, call it sexist, call it ignorant. Pink is pink, okay? It�s an ugly color to begin with, which is why only women can pull it off. You start dressing guys up in ugly colors, and you know what they look like? They look like ugly guys.
They look like what would happen if Gremlins took over the Barbie factory. They look like idiot douche-bags. I�ve heard arguments that boys can�t like pink because they�re raised to think it�s sissy. I disagree. I think that pink is considered a girl color in the first place because at some point, two guys were standing around, and one put on a pink shirt and went, �Hey, how do I look in this?�
And the other guy, he�s like, �Wow. That�there�s really�it looks like complete shit.�
�It really does, doesn�t it? This is the last time I listen to my girlfriend. I think you were right about her trying to take my balls away, by the way.�
�Yeah, the shirt proves it, I think.�
�It does. It really does.�
Tough guys wear pink. I wanted to shove the little bastard down. Maybe he can wipe away his tears with his tough guy shirt.
I looked at movies and found some I wanted�about six thousand dollars� worth.
And then I decided to go get some food. Quick stop at McDonalds, and then�because it was on my shopping list, anyways�a bottle of whiskey. Back to the car with my lunch and my evening�s entertainment. I took one bite of my cheeseburger, and my phone rang.
�I�m ready,� my princess said.
Back to the damn bridal shop. She was waiting in line. There were two people in front of her, with two cashiers helping. The line was not moving. Three minutes pass.
At this point, I�m being kind of a dick, because I got that first bite of cheeseburger (a break from the salad and all of that bullshit that I�ve been eating so as to lose a little weight before the wedding), and I�m really hungry for the rest of it. Another three minutes, and I�m not being a dick anymore, but honestly curious about why I�m still standing here.
�This line hasn�t moved,� I say to my princess.
�I can see that.�
�What�s going on?�
�They�re talking.�
�That�s the problem with chick stores�too much talking, not enough action.�
She gives me her you�re-a-complete-idiot-but-I-love-you-anyway smile. �Do you think it�s a good idea to make sexist jokes in here?�
�I don�t really like to think about good and evil,� I say. �That�s a terrible dress over there�that green one? Must be for a bridesmaid, huh?�
�It�s a terrible color�the stains will never come out, you know what I�m saying?�
The cashier looks up at me and I tip her a wink. You wouldn�t believe how fast that chick starts ringing people up after I start talking about reasons why my genitalia is so small.
�Did you see how fast she was trying to get us out of there?� my princess asks as we walk across the parking lot. She�s laughing, instead of pissed off, and I think again about how much I love her.
�All part of my plan.�
Tough guys wear Paisley.