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Constitutive phosphorylation of the mTORC2/Akt/4E-BP1 pathway in newly derived canine hemangiosarcoma cell lines
Canine hemangiosarcoma (HSA) is a malignant tumor with poor long-term prognosis due to development of metastasis despite aggressive treatment. The phosphatidyl-inositol-3 kinase/Akt/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway is involved in its endothelial pathologies; however, it remains unknown how this pathway plays a role in canine HSA. Here, we characterized new canine HSA cell lines derived from nude mice-xenografted canine HSAs and investigated the deregulation of the signaling pathways in these cell lines.
Seven canine HSA cell lines were established from 3 xenograft canine HSAs and showed characteristics of endothelial cells (ECs), that is, uptake of acetylated low-density lipoprotein and expression of canine-specific CD31 mRNA. They showed varied morphologies and mRNA expression levels for VEGF-A, bFGF, HGF, IGF-I, EGF, PDGF-B, and their receptors. Cell proliferation was stimulated by these growth factors and fetal bovine serum (FBS) in 1 cell line and by FBS alone in 3 cell lines. However, cell proliferation was not stimulated by growth factors and FBS in the remaining 3 cell lines. Phosphorylated p44/42 Erk1/2 was increased by FBS stimulation in 4 cell lines. In contrast, phosphorylation of Akt at Ser473, mTOR complex 1 (mTORC1) at Ser2448, and eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1) at Ser65 was high in serum-starved condition and not altered by FBS stimulation in 6 cell lines, despite increased phosphorylation of these residues in normal canine ECs. This suggested that the mTORC2/Akt/4E-BP1 pathway was constitutively activated in these 6 canine HSA cell lines. After cell inoculation into nude mice, canine HSA tumors were formed from 4 cell lines and showed Akt and 4E-BP1 phosphorylation identical to the parental cell lines.
Our findings suggest that the present cell lines may be useful tools for investigating the role of the mTORC2/Akt/4E-BP1 pathway in canine HSA formation both
Hemangiosarcoma (HSA) is a malignant tumor derived from endothelial cells (ECs). Canine HSAs easily metastasize to other organs, and the mean survival time is less than 6 months even with surgical and chemotherapeutic interventions
Vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF), along with their receptors, are overexpressed in human angiosarcomas and canine HSAs
mTOR, a serine/threonine kinase, is highly conserved among animal species and regulates cell growth and cell cycle progression by controlling cap-dependent translation
Because of the limited availability of human angiosarcoma
Cell culture
To establish canine HSA cell lines, we used 3 xenograft canine HSA tumors, which were established from 3 spontaneous canine HSAs as described previously
For measuring the growth curve and population doublings, the established cell lines were plated in 24-well plates (Thermo Scientific) at 5000 cells/well in 1 mL of Medium 199 containing 10% FBS. The cells were trypsinized and counted with a hemocytometer using trypan blue every 24 h. Triplicate wells were used for counting each cell line.
To examine the uptake of the acetylated low density lipoprotein (Ac-LDL) in HSA cell lines, subconfluent cells were incubated with 10 μg/mL DiI-Ac-LDL (Biomedical Technologies Inc., MA, USA) at 37°C for 4 h in Medium 199 according to the manufacturer's instructions. After washing, the cells were observed with an inverted fluorescent microscope (Biozero BZ-8000, KEYENCE, Osaka, Japan) with a rhodamine filter. Human umbilical vein endothelial cells (HUVECs, Cell Applications Inc., CA, USA) were purchased and used as a positive control.
For measuring growth factors in cell supernatant, HSA cell lines were cultured under standard conditions in Medium 199 containing 10% FBS. After incubation for 72 h, the plates were washed with Hanks' Balanced Salt Solution (HBSS, Sigma-Aldrich, MO, USA), and the medium was changed to Medium 199 containing 1% FBS. After further incubation for 24 h, the supernatant was stored at −80°C. The cells were trypsinized and counted with a hemocytometer using trypan blue. VEGF-A and bFGF concentrations in cell supernatant were determined using commercial ELISA kits for humans (Quantikine, R&D Systems, MN, USA) according to the manufacturer's instructions since these kits were previously shown to have cross-reactivity with canine growth factors
Canine HSA cell lines were cultured to subconfluence under standard conditions in Medium 199 containing 10% FBS and were used for protein expression for VEGF-A and bFGF. After washing with phosphate-buffered saline without Ca2+ or Mg2+ [PBS (−)], the cells were incubated with Protein Block Serum-Free (Dako, Kyoto, Japan) for 30 min at room temperature (RT). The cells were incubated overnight at 4°C with primary antibodies for VEGF-A (mouse monoclonal antibody clone C-1, 1:50; Santa Cruz Biotechnology Inc., Santa Cruz, CA, USA) and bFGF (rabbit polyclonal antibody, 1:200; Santa Cruz Biotechnology Inc.). The specific protein signals were visualized using the 3,3′-diaminobenzidinetetrahydrochloride (Liquid DAB + Substrate Chromogen System, Dako). The cells were counter-stained with Mayer's hematoxylin.
Reverse transcriptase-polymerase chain reaction (RT-PCR)
Expression of mRNA for growth factors and their receptors was examined in the established cell lines. Total RNA was extracted from subconfluent cells grown in Medium 199 containing 10% FBS using TRIzol reagent (Gibco). Reverse transcriptase-polymerase chain reaction was performed as previously described
Cell proliferation assays
Cell proliferation assays were performed as previously described
Western blotting
Canine HSA cell lines were cultured to 70–80% confluence under standard conditions in Medium 199 containing 10% FBS. Cells were then washed with HBSS and the medium was replaced with Medium 199 containing 1% FBS. After serum starvation for 24 h, the medium was replaced with Medium 199 containing 1% FBS or Medium 199 containing 10% FBS for 30 min. For PTEN expression, subconfluent cells grown in Medium 199 containing 10% FBS were used. After washing with PBS (−), the cells were lysed with RIPA Lysis Buffer (Santa Cruz Biotechnology Inc.) with Phosphatase Inhibitor Cocktail 2 and 3 (Sigma-Aldrich). The concentrations of whole cell lysates were determined by modified Lowry method using the DC protein assay kit (Bio Rad, CA, USA). Equal amounts of protein (10 μg) were subjected to sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) under reducing conditions on 10% polyacrylamide gels. After separation by SDS-PAGE, the proteins were transferred onto a PVFD-membrane (Millipore, MA, USA). Membranes were blocked with 2% ECL Blocking Agent (GE Healthcare Life Sciences, Buckinghamshire, UK) in Tris-buffered saline containing 0.1% Tween 20 (TBS-T) for 1 h at RT. The membranes were then incubated overnight at 4°C with primary antibodies for phosphorylated Akt (p-Akt Ser473, rabbit monoclonal antibody clone D9E, 1:1000, and Thr308, rabbit polyclonal antibody, 1:500; Cell Signaling Technology, MA, USA), Akt (rabbit polyclonal antibody, 1:1000; Cell Signaling Technology), p-p44/42 Erk1/2 (Thr202/Tyr204, rabbit polyclonal antibody, 1:1000; Cell Signaling Technology), p44/42 Erk1/2 (rabbit monoclonal antibody clone 137F5, 1:1000; Cell Signaling Technology), p-mTOR (Ser2448, rabbit monoclonal antibody clone D9C2, 1:1000; Cell Signaling Technology), mTOR (rabbit monoclonal antibody clone 7C10, 1:1000; Cell Signaling Technology), p-p70S6K (Thr389, mouse monoclonal antibody clone 1A5, 1:1000; Cell Signaling Technology), p70S6K (rabbit monoclonal antibody clone 49D7, 1:1000; Cell Signaling Technology), p-4E-BP1 (Thr37/46, rabbit monoclonal antibody clone 236B4, Thr70, rabbit polyclonal antibody, and Ser65, rabbit polyclonal antibody, all 1:1000; Cell Signaling Technology), 4E-BP1 (rabbit monoclonal antibody clone 53H11, 1:4000; Cell Signaling Technology), and PTEN (mouse monoclonal antibody clone A2B1, 1:200; Santa Cruz Biotechnology, Inc.). β-actin (mouse monoclonal antibody clone AC-15, 1:3000; Sigma-Aldrich) was used as a loading control. The specific protein signals were visualized with horseradish peroxidase-conjugated secondary antibodies using the ECL Plus Western Blotting Detection System (GE Healthcare). CnAOECs were used to examine the protein expression for normal canine ECs.
Inoculation of cells and immunohistochemical staining
The established cell lines were harvested during logarithmic growth and prepared for injection in mice. Before injection, cells were trypsinized, counted, and washed twice with sterile PBS (−). A total of 1 × 106 cells were suspended in 0.2 ml of PBS (−) and injected subcutaneously into the right and left dorsal area of the trunk of 3-week-old male KSN/Slc mice. Five mice were used for each cell line. The mice were observed for tumor development twice a week, and the size of the resulting tumor was measured. After 9 weeks, or when the tumors grew to 10 mm in diameter, the mice were humanely sacrificed, and the tumors were immediately removed. If a detectable tumor was not formed in the mice within 30 days, the mice were sacrificed at this time. The removed tumors were fixed in 10% neutral buffered formalin, embedded in paraffin, sectioned, and stained with hematoxylin and eosin (HE) or used for immunohistochemical staining. Immunohistochemical staining was performed for CD31 (prediluted mouse monoclonal antibody clone JC70A; Dako), von Willebrand factor (vWF, prediluted rabbit polyclonal antibody; Dako), Ki-67 antigen (mouse monoclonal antibody clone MIB-1, 1:25; Dako), p-Akt (Ser473, rabbit polyclonal antibody, rabbit monoclonal antibody clone D9E, 1:50, Thr308, rabbit polyclonal antibody, 1:50; Cell Signaling Technology), and p-4E-BP1 (Thr37/46, rabbit monoclonal antibody clone 236B4, 1:1600; Cell Signaling Technology) on all tumors formed from the cell injections. The experiments were performed according to the guidelines for the care and use of laboratory animals and approved by the Committee for Animal Research and Welfare of Gifu University (No. 08015).
Statistical analysis
Morphology and growth of canine HSA cell lines
After 60 passages, 3 cell lines were established from the 3 xenograft tumors (Ju, Re, and Ud). After cloning, 7 sub-lines with differential morphologies were established from these 3 initial cell lines (Figure
Figure 1
Morphology, DiI-Ac-LDL uptake, and immunocytochemical staining for VEGF-A and bFGF of canine HSA cell lines.
Morphology, DiI-Ac-LDL uptake, and immunocytochemical staining for VEGF-A and bFGF of canine HSA cell lines. ( A) Morphological appearance and uptake of DiI-Ac-LDL (right bottom) of established canine HSA cell lines. Canine HSA cell lines were grown in Medium 199 with 10% FBS. Each cell line exhibited a different morphology. Bars = 50 μm. Right bottom; Uptake of DiI-Ac-LDL in KDM/JuA1. Bar = 25 μm. ( B) Immunocytochemical staining for VEGF-A and bFGF. The cytoplasm of cells showing positive staining with VEGF-A in KDM/JuA1 and bFGF in KDM/Re12. Bars = 50 μm.
Each sub-line showed variable anchorage-dependent growth as shown in Figure
Figure 2
Cell growth under standard conditions.
Cell growth under standard conditions. Growth curves of canine HSA cell lines. Each cell line was plated at 5000 cells/well in 1 mL of Medium 199 containing 10% FBS. The cells were trypsinized and counted with a hemocytometer using trypan blue every 24 h.
Expression of growth factor and growth factor receptor
The expression levels of mRNA for growth factors and their receptors were different among the cell lines as measured by RT-PCR (Figure
Figure 3
mRNA expression of canine HSA cell lines.
mRNA expression of canine HSA cell lines. RT-PCR analysis of the expression of endothelial cell-specific markers (CD31 and vWF), growth factors (VEGF-A, bFGF, HGF, IGF-I, EGF, and PDGF-B), and their receptors (Flt-1, Flk-1, FGFR-1, c-Met, IGF-IR, EGFR, PDGFR-α, and PEGFR-β). Total RNA was extracted from subconfluent cells grown in Medium 199 with 10% FBS using TRIzol reagent. β-actin was used as a loading control. mRNA extracted from canine spleen was used as PC, and water was used instead of mRNA as NC. Abbreviations: PC, positive control. NC, negative control.
One cell line (KDM/Re12) had a VEGF-A concentration of 201 pg/106 cells for 24 h in the cell supernatantas measured by ELISA, but bFGF was not found in the supernatant of any cell line. Immunocytochemical investigations for VEGF-A and bFGF revealed weak to moderate expression of these proteins observed in the cytoplasm of the cell lines (Figure
Effects of growth factors on cell proliferation
After 24 h of serum starvation, canine HSA cell lines showed differential response to growth factors, including recombinant human VEGF, bFGF, IGF-I, HGF, EGF, and PDGF-BB, recombinant canine VEGF and HGF, and to FBS as assessed by the WST-1 assay. All the cell lines could proliferate even in serum-starved condition. In KDM/JuB4, which expressed mRNA for all receptors except PDGFR-β, cell proliferation was stimulated by all growth factors except IGF-I and PDGF-BB in a dose-dependent manner, and by FBS. In KDM/JuA1, KDM/Re12, and KDM/Re21, cell proliferation was stimulated only by FBS and not by any growth factors even though these cell lines expressed mRNA for their receptors. Cell proliferation of KDM/JuB2, KDM/Ud2 and KDM/Ud6 was not stimulated by any of the growth factors or by FBS. Similar results were obtained from triplicate experiments. In CnAOECs, cell proliferation was stimulated by all growth factors except PDGF-BB and by FBS (data not shown). Figure
Figure 4
Cell proliferation in the presence of growth factors.
Cell proliferation in the presence of growth factors. Typical results of cell proliferation assays after incubation with recombinant human VEGF. Each cell line was plated at 1 × 103 cells per well in 200 μL Medium 199 containing 10% FBS in 96-well plates for 24 h. After 24 h-serum starvation, 0, 1, 10, 50, or 100 ng/ml of recombinant growth factor in Medium 199 containing 1% FBS was added to the cells, or the medium was changed to Medium 199 containing 10% FBS for 72 h. The relative viable cell number was assessed by the WST-1 assay. *; p < 0.05 compared with cells that were not exposed to growth factor.
Effects of serum stimulation on the MAPK/Erk and AKT/mTOR pathways
Because cell proliferation was stimulated by FBS in 4 cell lines, we further investigated the effect of FBS on the MAPK/Erk and Akt/mTOR pathways, which are major signal transduction pathways associated with cell proliferation
Figure 5
Effects of serum stimulation on the MAPK/Erk and AKT/mTOR pathways.
Effects of serum stimulation on the MAPK/Erk and AKT/mTOR pathways. ( A) Western blot analysis for the expression of Erk, Akt, mTOR, p70S6K, and 4E-BP1. Canine HSA cell lines were grown in Medium 199 with 10% FBS. After 24 h-serum starvation, the medium was replaced with Medium 199 containing 1% FBS or Medium 199 containing 10% FBS for 30 min. The total protein was then extracted using RIPA Lysis Buffer, and equal amounts of protein (10 μg) were subjected to western blot analysis. β-actin was used as a loading control. ( B) Western blot analysis for the expression of PTEN. The total protein was extracted from subconfluent cells grown in Medium 199 with 10% FBS using RIPA Lysis Buffer, and equal amounts of protein (10 μg) were subjected to western blot analysis. β-actin was used as a loading control.
Deletion or mutation of PTEN is reported in some types of tumors, including vascular tumors
Tumor formation in nude mice
After subcutaneous injections of cells from the various cell lines into KSN/Slc mice, tumor masses were formed in all the nude mice that had been injected with KDM/JuA1 or KDM/Re21 cells, and in 2 and 1 nude mice that had been injected with KDM/JuB2 and KDM/JuB4 cells, respectively (Table
Figure 6
Histology and immunohistochemical staining for EC markers and Akt/4E-BP1 in tumors formed from cell injections.
Histology and immunohistochemical staining for EC markers and Akt/4E-BP1 in tumors formed from cell injections. Tumors formed after injection of 1 × 106 cells in the right and left dorsal area of the trunk of 3-week-old male KSN/Slc mice. (A- D) Histological features of formed tumors (A: JuA1, B: JuB2, C: JuB4, D: Re21). Hematoxylin and eosin staining; bars = 50 μm. The neoplastic cells had spindle to polygonal-shaped cytoplasm with oval nuclei, forming some areas of vascular clefts of channels. (E-S) Immunohistochemical results of CD31, vWF, Ki-67, p-Akt Ser473, p-Akt Thr308, and p-4E-BP1 Thr37/46 in the formed tumors. (E) The membrane of the tumor cells show positive staining with CD31 (JuA1). ( F) The cytoplasm of the tumor cells show positive staining with vWF (Re21). ( G) The positive staining of Ki-67 MIB-1 clone in the nuclei of tumor cells indicates that the tumor is not derived from the mice (JuB2). ( H- K) All HSA tumors that developed showed moderate (I: JuB2, J: JuB4, and K: Re21) to strong (H: JuA1) expression for p-Akt Ser473 in the cytoplasm and nuclei. (L- O) HSA tumors that developed showed moderate (N: JuB4) to weak expression (L: JuA1 and M: JuB2), and one cell line (O: Re21) showed no expression of p-Akt Thr308. (P- S) All HSA tumors showed strong cytoplasmic and nuclear expression of p-4E-BP1 Thr37/46 (P: JuA1, Q: JuB2, R: JuB4, and S: Re21). Immunohistochemical staining; bars = 50 μm (G) and 25 μm (E, F, H- S).
All tumors that formed were examined further for expression of the Akt/4E-BP1 pathway. Moderate to intense degrees of phosphorylation of Akt at Ser473was observed in both the nuclei and cytoplasm in all tumors (Figure
We established 7 canine HSA cell lines from nude mice-xenograft canine HSAs
The established canine HSA cell lines expressed differing levels of mRNA for a variety of growth factors and their receptors. Although receptors were expressed in most of the cell lines, cell proliferation was stimulated only by the associated growth factors in the case of KDM/JuB4, in which proliferation was also stimulated by serum. Stimulated proliferation of 3 cell lines was observed in the presence of serum alone. A previous study with a canine HSA cell line showed that proliferation was stimulated by serum and the same growth factors that we used except for human VEGF and PDGF-BB
In the present study, VEGF was detected in culture supernatant only in one cell line, even though mRNA and protein for VEGF was detected in all cell lines, and bFGF was not detected in the supernatant of any cell lines, including two cell lines that expressed mRNA and protein for bFGF. VEGF is known to regulate normal angiogenesis
The phosphorylation of Akt at Ser473 was not affected by FBS stimulation in all cell lines except KDM/Re12. In addition, the phosphorylation of mTORC1 at Ser2448 and 4E-BP1 at all residues was unchanged in all cell lines. In normal canine ECs, the phosphorylation of Akt at Ser473, mTORC1 at Ser2448, and 4E-BP1 at Ser65 was increased in the presence of FBS, but not phosphorylation of 4E-BP1 at Thr37/46 or Thr70. 4E-BP1 is known to be sequentially phosphorylated on three residues: phosphorylation of Thr37/46 is followed by Thr70 and then Ser65
Although 4E-BP1 was constitutively activated independent of FBS, cell proliferation was stimulated by serum in 4 cell lines. This stimulation seemed to be related to increased phosphorylation of p44/42 Erk1/2 Thr202/Tyr204, similar to that of normal canine ECs. The MAPK/Erk pathway regulates cell proliferation differently from the PI3K/Akt pathway
As opposed to phosphorylation of Akt at Ser473, the phosphorylation of Akt at Thr308 was affected by FBS stimulation and seemed to be correlated with the phosphorylation of p70S6K. Akt is usually phosphorylated at Thr308 by 3- phosphoinositide-dependent kinase, whereas Ser473 is phosphorylated by mTORC2
Deletion or mutation of PTEN is known to cause constitutive activation of the PI3K/Akt pathway in some types of tumors, including vascular tumors
After cell injections into nude mice, HSA tumors developed from 4 cell lines. In these mice with developed tumors, no metastatic lesion was observed, similar to that of original canine HSA xenograft models
We have established 7 canine HSA cell lines from 3 xenograft canine HSAs. These cell lines showed diverse morphologies and mRNA expression levels for VEGF-A, bFGF, HGF, IGF-I, EGF, and PDGF-B and their receptors. Cell proliferation was stimulated by these growth factors and FBS in one cell line, was stimulated by FBS alone in 3 cell lines, and was not stimulated by either growth factors or FBS in the remaining 3 cell lines. Phosphorylation of p44/42 Erk1/2 was increased in the presence of FBS in 4 cell lines and seemed to be related to serum-dependent proliferation. In contrast, phosphorylation of Akt at Ser473, mTORC1 at Ser2448, and 4E-BP1 at Ser65 was not altered by FBS stimulation in 6 cell lines, suggesting that the mTORC2/Akt/4EBP1 pathway was constitutively activated in the present cell lines. After cell injection into nude mice, canine HSA tumors were formed in 4 cell lines. These tumors showed similar expression levels for phosphorylated Akt and 4E-BP1 as the original cell lines. Therefore, the present cell lines are useful models to investigate the role of the mTORC2/Akt/4E-BP1 pathway in canine HSA in both
Competing interests
The authors declare that they have no competing interests.
Authors' contributions
AK was involved in study design, establishment of cell lines, and histopathology. HS and SAA conceived the aims of study and participated in its design and coordination. AH and TY participated in study coordination. All authors have read and approved the final manuscript.
This study was supported by Grants-in-Aid for Scientific Research (C) Grant No. 23580439 from the Japan Society for the Promotion of Science.
Miscellaneous Tumors
Detection and characterization of vascular endothelial growth factors and their receptors in a series of angiosarcomas
Expression of vascular endothelial growth factor, basic fibroblast growth factor, and their receptors (flt-1, flk-1, and flg-1) in canine vascular tumors
Roles for deregulated receptor tyrosine kinases and their downstream signaling molecules in hematologic malignancies
Ras/Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR inhibitors: rationale and importance to inhibiting these pathways in human health
The vascular endothelial growth factor receptor KDR activates multiple signal transduction pathways in porcine aortic endothelial cells
Differential expression of active mitogen-activated protein kinase in cutaneous endothelial neoplasms: implications for biologic behavior and response to therapy
Transformation of chicken cells by the gene encoding the catalytic subunit of PI 3-kinase
Mutations of phosphatase and tensin homolog deleted from chromosome 10 in canine hemangiosarcoma
Mutation of the PTEN gene in a human hepatic angiosarcoma
Angiosarcoma: clinical and molecular insights
Targeting mTOR: prospects for mTOR complex 2 inhibitors in cancer therapy
Upstream and downstream of mTOR
Mammalian target of rapamycin is a direct target for protein kinase B: identification of a convergence point for opposing effects of insulin and amino-acid deficiency on protein translation
Hierarchical phosphorylation of the translation inhibitor 4E-BP1
eIF-4E expression and its role in malignancies and metastases
Significance of the expression of phosphorylated signal transducer and activator of transcription-3, -Akt, and -cyclin D1 in angiosarcoma
The significance of p53 and retinoblastoma pathways in canine hemangiosarcoma
Phosphorylation and regulation of Akt/PKB by the rictor-mTOR complex
Defining the role of mTOR in cancer
Establishment and characterization of an angiosarcoma-derived cell line, AS-M
Establishment of a human hemangiosarcoma cell line (ISO-HAS)
Canine malignant hemangiosarcoma as a model of primitive angiogenic endothelium
Biological and molecular characterization of a canine hemangiosarcoma-derived cell line
Establishment of canine hemangiosarcomaxenograft models expressing endothelial growth factors, their receptors, and angiogenesis-associated homeobox genes
High urine concentrations of basic fibroblast growth factor in dogs with bladder cancer
Plasma vascular endothelial growth factor concentrations in healthy dogs and dogs with hemangiosarcoma
Identification and isolation of endothelial cells based on their increased uptake of acetylated-low density lipoprotein
Distinct functional significance of Akt and mTOR constitutive activation in mantle cell lymphoma
Immunohistochemical detection of cell growth fraction in formalin-fixed and paraffin-embedded murine tissue
Different immunoreactivity of endothelial markers in well and poorly differentiated areas of angiosarcomas
CD31 immunoreactivity in mesenchymal neoplasms of the skin and subcutis: report of 145 cases and review of putative immunohistologic markers of endothelial differentiation
An immunocytochemical assessment of 19 cases of cutaneous angiosarcoma
Electron microscopic localization of factor-VIII-related antigen in adult human blood vessels
Interleukin-12 inhibits tumor growth in a novel angiogenesis canine hemangiosarcomaxenograft model
Expression of vascular endothelial growth factor in human umbilical vein endothelial cells stimulated with interleukin-1alpha–an autocrine regulation of angiogenesis and inflammatory reactions
Possible participation of autocrine and paracrine vascular endothelial growth factors in hypoxia-induced proliferation of endothelial cells and pericytes
The biology of vascular endothelial growth factor
Regulation of 4E-BP1 phosphorylation: a novel two-step mechanism
Angiotensin IV enhances phosphorylation of 4EBP1 by multiple signaling events in lung endothelial cells
Protein synthesis is resistant to rapamycin and constitutes a promising therapeutic target in acute myeloid leukemia
PHAS-I as a link between mitogen-activated protein kinase and translation initiation
Autocrine IGF-1/IGF-1R signaling is responsible for constitutive PI3K/Akt activation in acute myeloid leukemia: therapeutic value of neutralizing anti-IGF-1R antibody
Dual inhibition of PI3K and mTORC1/2 signaling by NVP-BEZ235 as a new therapeutic strategy for acute myeloid leukemia
Hypoxia-induced endothelial proliferation requires both mTORC1 and mTORC2


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Chapter 19
"I want to know about you and Tanith. How did you two wind up with Ryuu?" Ladon sighed, looking up from the cricket he had been messing with. I had found it in the backyard and brought it up here to play with.
"That is a long story. Let's see, where to start. Well, our village was much like yours, a small village living in fear of dragons. Unlike yours though, we had been attacked everyday. Something was always either destroyed or killed. The village men had finally become sick of it and decided that the next dragon they found would be killed in the most evil of ways.
"Tanith and I, meanwhile, had been fighting with our mother. When the villagers started their plans, she tried to make us leave. She refused to tell us why, just saying that we were in danger. We continued to refuse. After about a week, it started. I would wake up in the dead of night to horrible pain in my back or legs. Nothing would stop it. Our mother heard me one night and forced Tanith and I to leave.
"We had stayed near the village, watching the people we cared about be picked off, one by one. The pain would become worse every night. Tanith started to feel it too. A week after we had been banished, the pain started as soon as the sun went down. It lasted until the sun came back up, and when the pain left, I had become a dragon.
"One of the villagers had spotted me. The strongest of the men had come to fight me. Not knowing what was going on, my body responded automatically. I turned back into a human. I was weaker like that and the men surrounded me. Tanith stepped in and pretended she was a witch controlling me. The men backed off and we escaped.
"After studying our family history, I found out our father was a dragon. Our mother had fallen in love with him on a trip to the neighboring village. He warned her that when we turned sixteen, our dragon side would start to emerge. She thought it was us that attacked the village. Tanith and I wandered around until we met Ryuu. He listened to what we had to say and took us in. We have stayed with him since that day." He finished the story. He seemed unaffected by what he had just said.
"Oh Ladon, I am so sorry. No wonder you hated me so much when I called Tanith a monster." He looked up with a goofy grin, a cricket in his hand.
"But you trusted us eventually. I am glad you did too. You are a good friend, Amani." He looked down, "Your parents might treat you as mine did me if they find out what you are doing though." I shrugged and told him I didn't care, I would do it anyway.
"Did your village ever stop the dragon that attacked them?"
"Ryuu found out who it was. It turned out to be our father. Ryuu tried to make him stop, but he refused. He ended up killing our father." I looked out the window, towards the hill. Ryuu protected them, and he had been protecting our village too. Tanith and Ladon had been helping him out.
So who was attacking our village now? And why couldn't they figure it out? I paused thinking over the people who had died, it wasn't our village, it was me. Someone wanted to hurt me, or blame me. It would be easier to blame me if they made it seem a human killed the dead, instead of a dragon. So it wasn't just me they wanted to hurt. I glanced at Ladon again. Maybe they wanted one of the other dragons to be blamed too.
"That dragon that was killed, with all of the other people here, what did he look like as a human?" Ladon looked at me.
"I could show you."
I watched him warily, "I don't want to do that again.
"He shook his head, "They didn't warn you. Besides, I will be gentle. I promise." He waited for my answer. I reluctantly nodded. He moved closer to me and rested his hands against my ears. I closed my eyes and let the image slowly become clear. The boy had bright red hair, freckles dotted his nose, and the rest of his face.
"That is Simon. He would play with Peter and I when he came to buy something from our village. He was a dragon?" Ladon pulled back and nodded.
"Yes, he visited us sometimes. I am surprised he told you his real name though. Most make a new one up."
"You and Tanith told me yours, so did Ryuu."
"Yes, we told you ours, we just didn't tell you the dragons you talked to everyday had the same names. I don't know why Ryuu told you his. He normally doesn't."
"I don't know. I liked Simon though, he was a good friend."
"So even the dragon is connected to you. Maybe you ended up making another dragon angry somehow. You seem to attract them."
"Joy," I muttered. "Then you better be careful. He might go after one of you guys next." He nodded, watching me seriously. I leaned out the window, watching the birds fly across the sky.
"Alright, one more question and I will stop. Does Coda know?"
I could hear laughter from behind me. I scowled and turned around. Ladon shook his head and continued to chuckle. "Of course he knows. All animals can tell when a dragon is nearby. Unlike humans, they don't fear us. Well the occasional ones we eat do, but the others don't." Interesting, I thought.
A scream broke the peacefulness. I could tell instantly that it was Jasmine's mother. Without hesitating, I ran outside to the town center, trying to spot either Jasmine or her mother.

subset: commoncrawl


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Schedule: Practice starts at 4 p.m. and ends at 6:15 p.m. All practices, with the exception of two open scrimmages, are closed to the public.
What's new: The offense is ahead of the defense. It doesn't happen often, but the storyline has switched in Blacksburg. One of the nation's consistently best defenses is in a rebuilding mode, having to replace six -- and possibly seven starters, if Barquell Rivers is not cleared by the Boise State game. Meanwhile, the offense is loaded with a veteran quarterback in Tyrod Taylor and two 1,000-yard rushers in Darren Evans and Ryan Williams.
Sidelined: Redshirt sophomore backup center Michael Via (knee) and Rivers, who missed spring practices after surgery to repair his left quadriceps tendon. Via is expected back in the next week or two, and a school spokesman said Rivers will be cutting it real close to being cleared in time for the Boise State game.
Key battle: We need not mention the obvious (Williams vs. Evans), so let's go with defensive tackle. Kwamaine Battle finished spring practice with a slight lead for the job vacated by Cordarrow Thompson, but Antoine Hopkins will keep things interesting this summer. There will also be good competition at field corner between Jayron Hosley and Cris Hill.
New on the scene: Nick Becton at left tackle, where he takes over for Ed Wang. Becton won the starting job this past spring, and the coaches think Becton has the potential to be a three-year starter.
Breaking out: Defensive end Steven Friday. He made plays in every scrimmage this past spring, and is one player defensive coordinator Bud Foster is expecting to be a leader. He was named the most improved defensive player this spring and is capable of game-changing plays like forced fumbles. He was the top backup to Jason Worilds last year.
Don't forget about: Evans. Out of sight, out of mind, right? Well, Williams isn't the only talented back on this roster. Don't forget Evans became the first Hokies freshman to rush for 1,000 yards in a season, and at the time, his 1,265 yards was the highest season total in ACC history by a freshman. He finished spring ball listed as a co-starter with …
All eyes on: Williams. Until proven otherwise, he is the best player on this roster and has a legitimate shot at the Heisman Trophy this year. He rushed for a school-record 1,655 yards last year, also an ACC freshman record. He scored 22 touchdowns, including 21 rushing, breaking ACC season records in both categories.
Quotable: "Obviously the talent that I have is the best I've ever had at Virginia Tech from top to bottom. … The thing we are going to try to do as an offensive staff is to get more than one of them on the field at the same time. I think that will be a big help to us offensively and will stress some defenses." -- Running backs coach Billy Hite.


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The Irish love a good story. They are a lyric, storytelling people. Their storytelling tradition is full of the improbable, impossible and likely not quite so. So although I appreciate those whose commitment to veracity in historical matters leads them to be St. Paddy's Day debunkers each year, I feel they miss the point of [Read More…]
Irish Snakes Survive and Thrive: All Snakes Day
PantheaCon: Concerning Three Rituals
There were quite a few rituals at PantheaCon and unfortunately I couldn't make them all. I was determined that the rituals I did attend wouldn't be Wiccan so I could experience the rites of other Pagan religions. Here are my thoughts on the three rituals I was able to participate in over this hectic weekend. [Read More…]
Religion in the US Military: Comforts and Controversies
by Erynn Rowan Laurie Bill of Rights Amendment I Congress shall make no law respecting an establishment of religion, or prohibiting the free exercise thereof; or abridging the freedom of speech, or of the press; or the right of the people peaceably to assemble, and to petition the Government for a redress of grievances. Chaplains [Read More…]


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Wonderful Life - a Dash Companion
I thought of you again today
Reminded me how with time I've changed
If only you knew what you give to me. . .
It's a wonderful, wonderful life.
-Wonderful Life, Gwen Stefani
Kate shouldn't be so proud, but she is. She managed to get both kids to preschool and make it to the station on time - alone - for the third day in a row.
Her phone rings as she's getting espresso from the machine. She knows it's him, but lets it go to voicemail so she can finish making her coffee. He'll understand.
She burns her hand on the steamer in her eagerness to call him back; it's been a while since she did that. After Dash was born and before Rick left the precinct, he gave her private lessons on how to operate the espresso machine. Very private. It's seared into her brain, that hot, steamy lesson.
Kate grins to herself, sips at her cup, burning the tip of her tongue but eager for caffeine. She didn't have the time this morning to make any, plus that's always Castle's job.
She calls him back. He answers immediately. "Hey there."
"Mm, coffee," she murmurs.
She hears him laugh, rich and deep. "Sexy, coffee voice. I love it."
"So where are you?" she asks, heading towards her desk, the phone tucked between her ear and her shoulder. She logs into her computer, takes another short sip, rifles through the folders piled up in her inbox.
"I'm in Chicago. How'd it go this morning?"
"Mm, I got the kids to preschool all by myself."
He chuckles again. "Good job, Beckett." His voice wraps around her last name like a caress.
"No fair teasing me when I'm at work and can't do a thing about it," she husks.
His laughter this time is a little breathless, just how she likes it. "There are about, ah, six people around me right now. Phone sex is not ideal for me either."
"Who said anything about phone-" She glances around swiftly, lowers her voice. "Phone sex? You and your dirty mind."
"Uh-huh. You say that, but we both know better."
"Two more days," she sighs.
"Yeah. Oh, darn. Gotta go. Kiss the kids-"
"Love you."
"You too." She ends the call and puts her phone on the desk, works the kinks out of her neck by rotating her head side to side. She hasn't slept so hard in years. Must be having the bed all to herself and no furnace sleeping next to her all night, wanting to cuddle.
She grins, bites her lower lip as she checks the duty roster. She misses the furnace. And the cuddle. Funny enough.
She's stuffing a bagel with cream cheese into her mouth when her phone rings. Castle again. Weird. She didn't think she'd have to tell him to not call her during the middle of a case, middle of the day - he usually knows better.
She answers, chewing the dense mouthful as best she can around her greeting. "What's up?"
"Hey, uh, Kate?"
She swallows hard. "Castle. Why are you calling me?" she says, flicking crumbs off the financial records of their victim. Ryan walks back in with a bagel of his own - they've been in a bag in the break room fridge for who knows how long, but she and Ryan were both starving and it's fair game.
"Hey, yeah, the - the preschool just called me."
"What?" She drops the bagel, stands up from the conference room table. "Why? Why haven't they called me?"
"They usually call me first. I told them I'd have you call down there-"
"What's wrong?" Her stomach churns, the bagel a hard knot in her throat.
"Dashiell's sick."
She drops back into her seat, waving off Ryan. "Oh. Okay. All right."
"They think he has chicken pox."
She groans and buries her head in her hand. "Are you kidding me?"
"Yeah. Apparently, kids can get a light case if they're exposed to someone with the disease, and since he hasn't yet gotten the second dose-"
"He has until he's six. That's what Dr. DeLameran told me."
After that single answer, Castle is silent on the other end - silently not judging.
It was her call - her decision not to let Dashiell get the second dose of the vaccine just yet, not after the hellish week the kid had as a 14 month old when he got the first dose. Fever, rash, no sleep, and she swears, she will always believe, that the rash with fever he got was a direct result of his immune system going nuts.
He's a sensitive kid - his body reacts differently. She wants to say all this in her own defense, but of course, her son is sick at preschool and she needs to get off the phone and go pick him up.
"Okay. I'm on my way to get him."
"And Ella," he adds softly.
"What? Why Ella?"
Shiiiiip. She sighs, presses the heel of her hand into her eyebrow. "Good point. What am I going to do with Ellery? She hasn't gotten the shot either."
He's silent. Still not judging. She can hear her own mother's voice in her head though, I told you so.
"Okay, all right. I'll figure it out. It's just for two days. Castle, you go. Do. Whatever. I need to get the boys caught up on this-"
"Yeah, I know. Kate. I'm sorry. I wish I could-"
"Hey, no. Don't." She clenches a fist as she stands up again, gathering files together, grabbing her jacket off the back of the chair. She had a hard enough time convincing him to do the book tour in the first place. "We'll be fine. This is no problem. Castle. Go do your thing."
"You sure?"
"You think I can't handle my own kids?"
"Kate." Exasperated with her for it.
"I'm sure." She presses her phone to her ear with her shoulder to free up her hands, waves Esposito into the conference room. "I gotta go. I'll call you later."
"I can't get to my phone again until eight your time."
"I'll call at eight."
"Okay." He sounds reluctant to hang up. "But if you need me, text me, and I'll keep checking-"
"Castle. Go," she says softly, turning her back on the boys, closing her eyes so she can hear just him. Just him. "We're fine. I got this."
"I know. I just - I hate that Dash has chicken pox and you've got both of them by yourself-"
"I'll call my dad for help if I need it," she says quickly. "Now, seriously. Go."
"Bye." He ends the call this time, and she sighs, lowers her phone.
"What's up, boss?"
Beckett turns, levels her gaze on her team. "Okay. I need to take the next two days off. Dash has chicken pox."
Damn. She googled chicken pox before she left the station, and she totally should have caught it. Dash has been complaining about his ears hurting him for a week now - and apparently that's one of the early symptoms. And his sleep has been so good - another symptom.
If Castle had been here this past week, he would've caught it. She's fairly certain of that.
She pulls into the church's parking lot and gets out quickly. On the phone, Kim from the preschool was so nice, so understanding about Kate needing an hour to clear her desk and get down here, but she doesn't want to presume on them much more than she has to.
She checks her gun, makes sure it's snapped into the holster, and swipes the key card over the lock. The door gives a faint buzz and she yanks it open, heads inside. No one is at the front desk when she starts through the lobby, so she moves towards the director's office.
Kim comes out of a classroom instead though, snags Kate by the jacket. "Hey. He's in here. I kept Ellery away from Dash, just in case she hasn't gotten it yet."
"Oh, thank you," she says, and slips into the room after Kim. The lights are off and Dash is asleep curled up on his rest mat, his hair sticking to his temple with sweat. "Does he have a fever?" she whispers, creeping closer.
"Yeah. It's mild though. I didn't give him anything in case you have specific instructions from your doctor?"
"Dr. DeLameran told me to call back when I saw him myself." She crouches over Dash, brushes her fingers through his hair.
"He's got spots on his stomach and his back, a few along his shoulders."
Kate sighs and slides her hand under her son's shirt, bringing it up so she can look. "Oh. Yeah, poor baby. That's chicken pox alright."
"I'll go get Ellery, if you want to take him out to the car?"
"Thank you," Kate whispers back, smiling. "Can I take his rest mat too? Wash it."
"Yeah, definitely. His backpack is by the door. I'll go get Ellery." Kim slips back out of the room, leaving Kate alone with Dash in the dark.
She slides a hand under his neck, pulls him upright so she can scoop him up. Oof, he's heavy for such a skinny thing. She gets him into her lap, wraps the soft rest mat around him for warmth - it's brisk outside, an early spring day that could turn rainy at any moment - and then she struggles to her feet.
Kate carries him back out into the hallway, through the lobby, pushing open the door with her hip and digging for her keys. She remote unlocks the car, balances Dash as she opens the back door, then props him up with a knee while she tries to lower him into the booster seat.
She nearly hits his head on the frame, manages to crack her own instead, and then pinches her finger in the seatbelt. She sucks on her maimed digit, wincing as her forehead throbs - it will bruise for sure - and then shuts the door softly on a still-sleeping Dashiell.
Which is totally unheard of. Dash never sleeps through anything. He's definitely a sick kid.
When Kate gets back inside the preschool, it's Kelly bringing Ellery out into the lobby. Kate jerks to a stop and puts a hand to her throbbing head, then lowers herself down next to her daughter, giving Kelly a smile of thanks.
"Hey, baby girl. Dash got sick. How are you feeling?"
Ellery stares at her, mouth in a firm line. But she reaches out a little finger and traces it over Kate's forehead.
"Yeah, ouch. I bumped my head-"
Ella leans in and kisses it, pulling back with a smile.
Kate sighs and smiles back, brushing a hand through Ellery's dark hair. "Thank you, baby. I needed that. You feel ok?"
Ella nods once, then peers around Kate as if looking for her brother.
"He's in the car. You ready to go home?"
"Actually, Kate-" Kelly starts.
Kate glances up at the woman, surprised. Kelly is friendly with her here, of course she is, but she's been dating Kate's father for the last few years and it's always been rather awkward. Kate just isn't sure what to do with the woman, how to act. Does she ask Kelly how her father is doing, or does she pretend that Kelly hasn't been spending her nights at Kate's father's house?
"Hey, Kelly," she says, standing back up, catching hold of Ella's hand, smoothing her thumb over her daughter's fingers.
"I was thinking - I figured you'd call Jim, your dad, right?"
"I haven't yet. But I think I'll have to," Kate says. It is so very weird to talk about her family with Kelly, not that Kelly isn't nice and so very sweet to Kate's kids, but Kate just keeps forgetting that Kelly probably knows quite a whole lot about all of them.
"Why don't I take Ellery home with me? To your dad's."
Home? To her dad's? Those . . . those words are synonymous now?
Kate rubs at her forehead, wincing, tries to use the flare of pain to clear her head. "Uh. Well. I don't want to pull you away from your job-"
"I talked to Kim and she'll take my class for the rest of the day. But only if you're comfortable with it, Kate."
Oh man, she's just too nice. Too nice. Kate can't even figure out a way to say no because she really, really wants to say yes. Yes, please take Ellery and keep her out of Dashiell's germy range of fire. Because if those two are at home together, Kate knows there is absolutely no way she can keep them apart.
Last night, Ellery was using Dash like a stepstool in front of the pantry, aiming for the nutella, probably. Kate caught them right before Ella could grab it or fall on her head. Although, to be fair, Ellery's got some natural balance and grace. Dashiell would have fallen. Probably not Ellery.
Which might be why they were working together on that one. Smart kids.
"Kate? You could put her carseat in my car; I could take her. I know your dad's got clothes and toys and stuff at his place."
Kate nods slowly. He does. And Dash has the freaking chicken pox. And it's a really miserable disease. Kate remembers it all too well - she got it twice. A light case both times, but bad enough to stick with her.
But, wow, Ellery's never been away from home like this before. Kate leans over and scoops her daughter up, cuddling her close. "Hey there, baby girl. Want to go visit Papa today?"
Ellery wraps her arms around Kate's neck, nuzzles in against her mother's skin.
"I need to take Dash home and get him some medicine and he's gonna be cranky and probably kinda whiny and mean because he's sick. So you want to go to Papa's with Kelly and have fun?"
Ellery lets go, leans back as if to study her mother. She uses two hands to push her hair back from her eyes, and Kate uses that opportunity to lean in and kiss her nose.
"What do you say, baby girl? You can spend the night with Papa. I bet he'll show you his workshop. You want to go?"
Ellery glances over at Kelly. The older woman holds out her arms and takes Ella when the girl leans over. It's not a definite yes, but it's probably all Kate's going to get from the silent one.
"Thank you, Kelly. Really. I - I really appreciate this-"
"Oh, it's nothing, Kate. Ella and I are good friends. Right, sweetheart?"
Ellery gives her a shy little smile and looks back at Kate.
"Oh, good. You guys will have fun then." Kate smooths down Ellery's hair, brushes her thumb over her daughter's cheek. She meets Kelly's eyes, tries to force some cheer into her smile. "Thank you. This helps me a lot. Tell my dad to call me?"
"Of course. And Ellery can call you too, whenever she likes. How's that, Ella?"
The little girl gives Kelly a huge smile, something like relief on her face, and it strikes Kate that Ellery probably feels like she's getting shuttled away, handed off. At least Kelly isn't a stranger. Actually, Ellery really does like Kelly, Kate remembers, and she seems at ease in her arms.
"Yeah, you better call me," Kate murmurs, leaning in to kiss Ella's cheek. "I love you, little cricket. Be good for Papa. Call me before bedtime, and I can tell you a story over the phone."
"Yeah," Ella says softly.
Kate grins widely, her heart fluttering at the sound. "Yeah." She clears her throat and turns to Kelly. "You have my cell phone number-?"
"I got it. We'll be fine."
"I know," Kate says, nodding at her. She does. "I just - she's never been away from home." Kate gives a soft laugh, but Kelly's eyes have turned tender, knowing.
Kate shakes it off, gives her daughter a big smile. "All right, let's get your car seat so you can go."
She turns and leads the way out.


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WHILE YOU WERE AT WORK: Three stories, one is true, guess which one to win!
.: getty :.
Despite reports to the contrary, KELLY ROWLAND did NOT secretly wed her fiance, TIM WITHERSPOON, in Costa Rica over the weekend!
.: getty :.
ADAM LEVINE says to BLAKE SHELTON: PAYBACKS are a BI&&&H! The Maroon 5 crooner had COW DUNG dumped all over BLAKE SHELTON'S pickup truck while parked at the set of the VOICE! It was payback for Blake tweeting out Adam's cell number, which caused Levine's phone to MELT DOWN!
.: getty :.
SOLANGE KNOWLES, who went OFF on brother-in-law JAY Z and her sister, BEYONCE in a violent fight caught on security cameras at a hotel in Manhattan, will be heading to rehab for alcohol and substance abuse issues and anger management therapy in the coming days.
Three stories. One is true. Get it right and score tickets to see Bastille at Patriot Center. Want help? Click here for the true story!


text:
Twenty Ways to Die
by: aishuu
Disclaimer/Notes: Bleach is owned by Kubo Tite. This fanfic takes canon and bends it quite a bit, since I'm sure more than a few of the Shinigami are nobles. Call it artistic license in pursuit of an interesting story. I feel like I should give sophiap part of the writer's credit, since she walked through this step by step with me.
Renji died young.
His father was a foot soldier in the shogun's army. The man was fond of drinking, and Renji learned to keep his head down when he came back from a campaign. Renji's older brother, all of four years his senior, walked with a limp because he hadn't been smart enough to.
His mother, a woman frail from carrying ten children – only three of which survived to be born – did her best to keep her husband happy, but some nights his father was in a foul temper, and she would retreat, leaving her children to fend for themselves. She would wait until after her husband was finished, and then help bandage whatever wound had been inflicted.
He remembered the night he died was in spring, with the scent of sakura on the air. His father had been home for two days from the most recent war, and Renji had been counting the days until he left.
He never figured out what set his old man off. What he did remember was the man's eyes, bloodshot and watery, as he advanced on Renji. He remembered crying out as his father's fist crashed into his face - then his chest, then up around his ears. He didn't remember actually dying – the next thing that was clear in his mind was staring up through the rickety buildings of Rukongai.
Renji was beaten to death by his father. It's only natural he has serious issues with authority. The strange thing was, it was his mother he never forgave.
Hanatarou was old, although he doesn't appear it.
Hanatarou died over a millennium ago during the Heian era, but he never mentioned his age or tried to take advantage of his supposed seniority, since he felt he hadn't done anything to earn it. Hanatarou barely remembered who he had been in his mortal life; it seemed that he had been patching the wounds upon shinigami for eternity.
He has risen through the ranks of the 4th mainly through longevity. When the person above him died, the promotion came as an afterthought as he filled in the vacated slot. He was good at his work, one of the best, or else he wouldn't have survived this long.
Even in the 4th, there was a high casualty rate. The people responding to emergencies were often put in the line of danger and earn no glory when they die.
And that's only those that die outright.
It was not something they speak about, but the 4th has the highest suicide rate among the Gotei 13. There came a point when the mind can't take what it's seen, and needed an out. Hanatarou never reached that breaking point, but that may be because he held himself apart from his division members.
Hanatarou stopped trying to make friends after he had to cut the rope his fifth best friend had been found hanging from. He couldn't save everyone, so Hanatarou healed, because the only alternative was worse.
Kiyone and Isane both died alone.
They were born in the mortal world to a family of traders, and lived a good, although modest, life. Back then many children didn't make it to majority, and Isane fell ill when she was ten. She lingered on her sickbed for nearly a week, but the malady got the better of her, though she did have time to promise she and Kiyone would find each other again.
It was a promise Kiyone clung to. For the next three years, she lived stubbornly, knowing her big sister wouldn't want her to give up. Then an illness took her as well, and she found herself alone in a strange new world.
When Isane arrived in the Soul Society, she was advised to forget her mortal family – but she was stubborn and didn't forget about them, least of all her sister. She spent years waiting, and then decades searching, but she never turned up a trace of her younger sister.
Frustrated, she decided to join the Gotei 13. As a shinigami, she will have more power to continue her quest. She gave her word, and she planned to keep it, even if she had to cross worlds to do it.
It proved to be a moot point.
On the first day at the academy, the two meet, both members of the same class. They didn't say anything, instead just reaching out to the other, wrapping themselves in a tight hug and another silent promise: they will never be separated again.
They know there is hope in the Soul Society, because they've lived a miracle.
Gin never told anyone how he died.
He liked to make up stories, telling Rangiku that he ended up dying in the Battle of Yamazaki, adding that he still felt the phantom of the wound when it rained; another time, he told Kira he was poisoned, which was why he refused to take the first bite at a meal.
The stories piled on top of each other, some outrageous, others plausible. The few shinigami who did exchange tales – and there were very few, since it was considered the height of rudeness to discuss someone else's death – accepted that it was just another quirk of the 3rd's captain. He was not known for his honesty.
Gin kept the truth a secret for himself, hidden behind his all-purpose smile. After a while, he started to wonder if his memory of death is real, or just another story he had created.
Rangiku starved to death in her mortal life; it was why the Soul Society came as such a bitter surprise to her.
She hadn't been old enough to understand what death was, or to philosophize about what happened after life finished. But the shinigami that had performed her soul burial had promised her she was going to a better place. She had believed him for all of a week. Then the familiar ache of hunger pulled at her.
If not for Gin, she would have given up all hope. Gin was the first person who ever really helped her. She never understood why he had chosen to do so since she was perceptive enough to know he never did anything without purpose, but she loved him for it.
Mayuri died in an accident, and he never quite came to terms with it.
Gunpowder, a new and fascinating invention, made its way to Japan during the late Sengoku period. Mayuri, son of a daimyo, became fascinated with it. It provided an easier way to hunt; it wouldn't be until later that it became a valuable tool of war.
Mayuri was one of the first Japanese gunsmiths, and one of the most successful. Using Western designs, he created his own weapons, adapted to designs that fit the slighter builds of the Japanese. He saw guns as a form of power. He recognized, as many did not, the role they could play in shaping the future. He wanted to be the best, because he wanted to rule.
Mayuri was very good at his work, quickly on the way to becoming a legend, but every man has his off day. Gunpowder, though, was an unforgiving subordinate, and his one off day resulted in an explosion that took out his entire smithy.
It was a painful death. He lingered for days, without hands or feet, mentally calculating what he had done wrong. Finally death took him, and he learned from that lesson.
Mayuri is determined to never die again. His research will lead him to true immortality.
Ikkaku held a party on the anniversary of his death.
Time was a strange thing in the Soul Society, but Ikkaku kept track of its passing, marking each year without fail. He has celebrated 299 "Death Days," and was planning on throwing a grand bash to mark his tricentennial in the Soul Society. Some people thought he was morbid, but when confronted, he merely shrugged and claimed that any excuse for a party is a good one.
What he doesn't say is that as long as he gets drunk enough, he could keep from remembering exactly how he went. After all, who in his right mind wanted to relive being tortured to death?
Hisagi died in battle.
He had joined the Shinsengumi because he believed in their cause; he loved his country, and didn't like the foreigners. For him, the choice was clear, written in black and white on his soul.
The battles he fought were fierce and furious, and the rules of the Shinsengumi made life simple. There was a right and wrong, a way things had to be done. It was a hard life, but he was fighting for something he believed in, and following leaders he could respect.
It was less than three months after he'd joined that his squad leader had fallen in battle. According to the code, all members of the unit were required to fight until they died on the spot.
He had done so, attacking members of the Mori clan who'd slain his leader. He was a good fighter, but a sword to the back had taken him before he'd managed to kill any of the enemies. Still, as he lay dying, he knew satisfaction for fulfilling his purpose, and following the Shinsengumi's code to the end.
Hisagi only realized much later how very naïve he'd been.
Hitsugaya died in fire.
He had been too young to understand why. The war had his community on rations, but that was the way he'd been raised, so he didn't know anything different. The planes that flew overhead on bombing runs were just a fact of life. He didn't bother worrying about the things he couldn't change. His main concern was if he had a crush on the girl who lived down the street.
Sitting in class, he listened as his teacher droned on and on about history. He tuned most of it out, tired from staying up late the night before, playing shougi with his grandfather. He'd been half asleep when the world suddenly changed.
He barely had time to register what was happening. There was no sound, just a flash of blue light and an intense heat that felt like falling into the core of the sun. Later on, he found out that he was merely one of many thousands who had been killed by Little Boy.
He knew it was silly, but while living in the first district in the Soul Society, he always felt overheated. He dressed in summer clothes, and drank many iced drinks, but nothing was able to make him feel cool.
It wasn't until he met Hyourinmaru that his fever finally broke.
Hinamori died in water.
Her family lived in a small fishing village. Like all of the children, she worked for her parents as soon as she could walk. She learned to swim even before she could walk. Those lessons made her feel prepared for anything the ocean could throw at her.
It was a perfectly fine day, and she and her younger brother were at the docks, repairing nets for her father. She had been daydreaming, thinking about the festival slated in three days, mechanically performing the work and not paying attention to her surroundings.
She only noticed the unusually low tide because she had to drag the nets further than she was accustomed to. Her brother complained about it, but she smiled and laughed at him, accusing him of being lazy. He'd sniffed and stopped speaking to her, going into a pout. She'd decided to let him sulk.
He was the one who broke the silence, like he usually did. "What's that, oneesan?" her brother asked, pointing toward the ocean. She barely had time to turn her head before the wave hit. It moved so fast.
She wasn't one of the lucky ones, the people who died instantaneously as the wave crashed down. She survived the initial impact, only to be swept out to sea. It felt like she spent an eternity clawing for the surface to no avail, but later she recognized that it was likely only a few minutes. A small girl didn't take long to drown.
At night she dreamed of that feeling, the burning sensation of her lungs as she struggled to hold her breath for just a little longer.
There were all kinds of stories about how Zaraki ended up in the Soul Society. The shinigami in the 11th invented wild stories about the battle and how many people he took with him. They believed he was a warlord or a bandit in his former life, and he let them think whatever they want, smirking every time he interrupted one of their speculative conversations.
A few of the braver ones tried to get a hint from him, but he told them he didn't exist until he joined the Gotei 13. Not even Yachiru knew about his death; it was a secret he was too ashamed to admit.
In truth, Zaraki died of consumption.
Zaraki feared no man, but the thought of illness caused him nightmares. He avoided Ukitake as much as possible because although he knew the 13th's captain wasn't contagious, he couldn't convince his subconscious of it. He remembered how his body failed him, coughing up blood and gasping for breath. He remembered his helplessness, and swore that will never happen again. The next time he died, he promised himself, he will go out in a blaze of blood and glory that the Soul Society will never forget.
Yachiru didn't remember how she died.
Her first memory was of blood, of living in the 79th District and meeting Zaraki. She remembered the number of clouds in the sky, the slightly shocked look in his eyes as he saw that she didn't fear him.
She didn't mourn for her mortal life; she had everything she needs and there's no point in asking for more. Yachiru didn't care how she died; it was more important to concentrate on living this life with Zaraki.
Tousen was born without sight, and died without ever seeing anything.
Growing up, people were not accepting of his disability. He was luckier than most in that his mother shouldered the burden of caring for him, but his world was a small place, limited to the two rooms of his mother's home. He grew to know those rooms better than most people would ever know anything, even with sight.
He had lived well, but in the end, his mother couldn't take it anymore. He died in his sleep, suffocating under a pillow his mother had held down on his face. He never learned this, believing that his body had just given out. He built his afterlife upon this lie.
In Soul Society, most physical imperfections were healed, but a few were not. There was plenty of theories why, but no one had any concrete proof one way or another. Tousen was one of those rare few who came to Soul Society blind. He vowed that the entire world would be his home, and set about learning it as thoroughly as he had those two small rooms.
Tousen didn't see his physical blindness as a liability. Instead, he believed he saw more clearly than anyone, since he was not blinded by false illusions.
Creating the illusion of his dead body actually made Aizen twitch.
There wasn't much that could shake him. Once, when he'd been young, he'd known fear. He faced it every time he went on assignment with his squad, wondering if this mission would be the one he wouldn't come back from. That was part of the reason he worked so hard to master his innate power. Aizen had no desire to become a ruler; his drive was instead fueled from a primal desire to survive.
Time had worn away his fear, and eventually he'd grown discontent. He hadn't realized that it was the uncertainty that had made the battles so exciting. Eventually his skill was such that there was no doubt if he would be one to live. He couldn't always save those in his charge, though, and that had led him to review his previous disdain of power for power's sake.
Seeing his body dead against the wall was a reality check. No matter how good he was, there was always the possibility that someone could bring him low. Death could happen, even to him. Then he dismissed the doubts in his mind.
He had no need of fear; only the mortal knew that emotion, and he was to become God.
Isshin was not dead, no matter what the Gotei 13 had listed in its records. Isshin left the Soul Society after meeting Masaki during a routine patrol, and never looked back.
He fell in love with her laugh, the way she smiled and the resulting sensation of lightheadedness it evoked in him. He made an insane, instantaneous and completely irreversible decision after seeing her – instead of heading straight home, he'd gone to Urahara's shop.
It had taken a while to get used to gigai, and not using his power. Urahara had been kind (for a bill Isshin spent years paying off), helping him forge a faux identity to suit his faux body. The first week he'd had doubts, but by the second, he was opening his own medical practice using the wisdom he'd gained over the centuries from close association with Unohana and his own good sense. It took him far more time to win Masaki's heart, but things won easily weren't worth cherishing.
Isshin mentally buried the man who served as captain, but from that death came the birth of a doctor – and later a husband and father. If anyone had asked, Isshin would have said it was more than a fair trade.
Yumichika died in squalor.
There had been a famine in the land, and rice was hard to buy. He'd worked in the fields, just a farmer, but was still starving since he wasn't allowed to eat the fruits of his own labors. The daimyo didn't care about the people under his rule; rice was power, and he wanted all of it.
Yumichika didn't understand any of the politics behind his life. All he knew was fighting for survival, a fight he lost. He died before he turned fifteen, and it had not been pretty. Burned by the sun, his ribs poking through in contrast to his distended stomach, Yumichika had been a pitiful sight.
It wasn't until he saw his reflection in Soul Society that he appreciated what had been done to him. He vowed that next time, he would be the one to take everything, to remake the world in his own image. He would not let others control him again.
Yumichika learned not to be upset about the way his mortal life had ended. He didn't resent the way he had been crushed down, because he had been weak. No, the thing that annoyed him was how ugly it had been.
Yumichika knew that the next time he died, it would be a beautiful spectacle.
Rukia and Hisana died together.
They were two siblings among many, Hisana the eldest and Rukia a babe of four months. Hisana was starting to think about marriage, and their mother figured it was good practice for Hisana to take care of her siblings. It was a day toward the end of summer when Rukia caught a cold. Usually they would go to the market with their mother, but someone had to stay and watch the crying child.
"Look after your sister," her mother commanded before leaving for the store, and Hisana had promised to do her best.
It wasn't a hardship. Rukia was a charming baby, aside from her occasional sniffles, and Hisana liked to make her giggle. They spent the morning playing peek-a-boo, Rukia gurgling in surprise each time Hisana peeked around her hands. It was a pretty normal day until the room begins to shake.
Hisana was no stranger to earthquakes; living in Tokyo made it a fact of life, but this one was different. She felt the ground drop beneath her feet and fear surged within her. Somehow she managed to push the terror down enough to grab Rukia, prepared to find someplace safe. The last thing she remembered was seeing the ceiling come toward them.
Hisana discovered that they had been lucky to die quickly. The tales of horrific fires she heard from other newly arrived souls made her glad that death had been merciful. It was the last bit of mercy they knew.
Life in the 79th was hard, and though she tried, Hisana discovered that she couldn't take care of Rukia and survive herself. So she abandoned Rukia, reasoning that most people in Soul Society are alone.
It was something she regretted from that moment on. She didn't go an hour without thinking about her sister, and if Rukia was still alive. She tried to rationalize her decision, but understood that her choice has branded her as unworthy of anything but scorn.
When she met Byakuya, she promised to be a good wife, but knew she'd already failed those duties before. Hisana wondered how he could love a woman whose word is worthless.
Byakuya took pride in his title. He was proud to be shinigami, proud to control the power that came from death.
He was tall and imposing, a figure that truly defines "grim reaper" whenever he was at work. Byakuya knew he must appear frightening to the souls who he laid to rest with a soul burial, but didn't care. Death, he believed, should not be comforting.
The nobility of the Soul Society have always been indifferent to the trauma souls feel when they make they transition. They had never died, and thus had no empathy. Byakuya believed, as did his entire family, that death was merely part of life and should be accepted philosophically.
It's not until he lost Hisana that he understood the pain death brought. While he had never died, not like most of his subordinates, he realized that there was more than one way to lose his life.
His title mocked his soul; he was god of nothing.
Shigekuni Yamamoto-Genryūsai died in his sleep.
In his life, he was a master general. He lived a good life, won many wars and had many children, but in the end, his body failed him. One night he went to bed, and woke up in what would become Rukongai. At the time, there was little organization, but he helped reform the society in his image.
Death is – or should be – the one universal truth. Even the greatest must fall to mortality, no matter which side of the Soul Society they're on.
It is a lesson he learned well. He made sure to discover how all his subordinates met their mortal ends, for it shaped their spirit in their afterlife.
Kaien died without regrets.
He'd been a noble of the Soul Society, and hadn't understood what death really was. He knew the system, believed in his place in it, and accepted that all he could do was his best.
That final battle, against the Hollow that robbed him of his wife, had been for his pride. He'd been enraged, and wanted to be the one to destroy the monster. He had, but it had cost him his life. But he had done it, restoring Miyako's honor while maintaining his own.
He'd never really thought of what would happen when he died. He knew how souls moved back and forth from the mortal realm to Soul Society, and had subconsciously assumed that he'd be part of that cycle. In the moment before he died, Kaien felt Rukia's hand on his back tremble, and he felt at peace.
He knew they'd meet in a future life, and he'd have the chance to thank her again for what she had done. Kaien died content, because there was someone who could carry on his will.


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"Every journalist who is not too stupid or full of himself to notice what is going on knows that what he does is morally indefensible. He is a kind of confidence man, preying on people's vanity, ignorance, or loneliness, gaining their trust and betraying them without remorse.
--Janet Malcolm, The Journalist and the Murderer, 1990"
AJ Strata is drumming up support to possible throw a little class action on the MSM because of all the recent "leak reporting", specifically by papers such as the NY Times and Washington Post.
AJ writes:
"A while ago someone suggested a way for 'We The People' to fight back as these treasonous liberals expose us to attack. The idea was to bring a class action law suit against the media outlets who recklessly expose our defense mechanisms to our enemies.
We don't need to win, as much as get millions and millions of people signing up against the New York Times, Washington Post, the reporters themselves. In my opinion these companies are impairing my civil rights by exposing me and my familiy to terrorist acts. I have the right to life, liberty and the pursuit of happiness, and the partisan actions of these leakers is putting all of this at risk.
These are not whistleblowers, they never show a single instance of wrong doing - just theories and conjecture. Their motivations are purely partisan politics.
Time for us to remind everyone the power is in the people. So if anyone knows how to start a law suit against these people please let us all know."
Suing the press - I like it, and it's not without precedent as any search of civil law cases will show, howbeit this would be a first on such a large scale.
Well it's been coming for a while.
The fact is that we are quickly running into a "civil war" of sorts between good effective journalism and political agendaism. Between the "freedom of the press" and "outright journalistic tyranny". of which in my opinion Edward R. Murrow cast the mold.
However, just as the sun rises in the east there have always been partisan reporters who worked with their own partisan editors on the left and right, and papers like the LA Times, NY Times, Washington Post have been and still are the primary "papers of the left". They have been for years.
Yet while as a conservative writer I have my fun with their reporting as a whole from time to time, I found absolutely vile the blatant reporting of classified and still operative information for apparently - at least in the case James Risen of the NY Times - no other reason than to make a buck.
Had the NY Times posted article number one as an excerpt to an upcoming book by Mr. Risen with the standard "Excerpt one of ___", at least it would have been intellectually honest. Perhaps the Times forgot that honesty is one of the five pillars of journalism. Fact is that Mr. Risen's initial and subsequent 'articles' have been nothing more than ill researched and uninformed partisan cheap shots taken at the President of the United States in a time of war for no other reason than to get Mr. Risen's political agenda across - and of course to sell a lot of books.
Nothing more and nothing less.
Which brings me back to AJ's idea. I believe a far more effective and a greater effort I think would be to file the class action against Mr. Risen himself as no doubt the Editors at the NY Times would immediately send him to pasture just as they did Judy Miller. Fact is that he would be quite on his own. Further it would be hard for him to defend his position with the standard "freedom of the press", as he is profiting from the freedom. Perhaps boycotts of any booksellers that peddle his book would send a message as well.
This brings me to a larger point. I believe that the age of "unaccountable" reporting may be coming to an end. The agenda manufactured and partisan media driven Plame Game will go down in the annals of history as journalism's 'Waterloo". The jailing of Judith Miller - not a isolated incident as journalist are jailed all the time for failure to identify sources - has become the new "plumline". Watch as see as these leak cases go forward as both writer and editors witness the prosecution.
Moreover, remember that today's modern monolith mass media outlets are "profit driven", and 2005 was not a banner year as all major newspapers as well as MSM TV outlets saw cutbacks, layoffs and scandals of their own.
I don't think this is was just a "bad year" or that the problem is isolated - I think the public by and large is on to their 'game' and quite frankly fed up.
The fact is that we do need a free press and I want a free press, but with freedom comes responsibility. I know a lot of secrets from my former occupation - many of which are still classified, some of which could still get people hung. Yet I don't need to tell them in order for the society to be "open".
From my one of my journalism professors of long ago on what to ask when deciding to do a story:
1. Is it true?
2. Is it important?
3. Do we really need to know - now?
I don't think Mr. Risen bothered to ask.
iraq Politics News murtha Able Danger Curt Weldon bush war on terror spying patriot act nsa CIA jonathan alter leakkrugman
On leakers and the MSMPosted by Jack Moss
"Every journalist who is not too stupid or full of himself to notice what is going on knows that what he does is morally indefensible. He is a kind of confidence man, preying on people's vanity, ignorance, or loneliness, gaining their trust and betraying them without remorse.


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External Affairs Minister S M Krishna also said that the use of terrorism as an instrument of state policy has no place in today's world and is self destructive.
"We are still waiting for Pakistan to act decisively to bring to justice the perpetrators of the mindless violence that was unleashed on Mumbai. We are still waiting," Krishna told reporters here.
He said the evidence given by the Home Ministry to Pakistan in the Mumbai terror attack case was sufficient for "any normal court" to prosecute the accused.
"I think the evidence provided by the Ministry of Home Affairs would be sufficient for any normal civilian court to prosecute the people involved in the conspiracy and the perpetrators of this crime," Krishna said.
"I once again call on our neighbour to bring the perpetrators of the crime to speedy justice," he said.


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The BTFD Wildland Strike Team is a team of firefighters who have obtained specialized training in fighting this type of fire. The team responds to local fires and is also prepared to be called upon to fight larger scale forest fires in the southeast region.
The team continues to train on these specialized skills to keep a constant rediness state. Firefighters wishing to be a part of the team are required to go through yearly testing as to be sure they are keeping themselves up to standards physically as well as knowing the skills needed to perform.
Richard Dollahan
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Jeff Kuehn
Dan Connelly
Derek Beeler
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Ted Lainge
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All content property of the Bluffton Township Fire District
© Copyright 2016
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If your DAW doesn't have MIDI note analysis built in, Insert Piz Here's Midi Chord Analyser could be a real help!
Some DAWs – Logic Pro, for instance – will tell you the MIDI note that's coming into the software, and also what the chord is or what it could be. Lots don't, though, so if you use Reaper, Ableton Live, or another DAW that leaves you in the dark, Midi Chord Analyser is perfect.
MIDI Chord Analyser
There's not much to say here – Midi Chord Analyser is a nice, simple utility plugin that'll tell you your chord, or if it's ambiguous give you a couple of options. It seems stable, and you can copy chord information out of the plugin in plain text which is a pretty nifty feature.
It doesn't have audio output so be careful where you place it on your insert chain; Midi Chord Analyser works best as the first device, before any instruments. Head on over to Insert Piz Here to grab it free for Windows and Mac!


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Tim Beckman Ranked #12
- Updated: April 24, 2014
Illinois head football coach Tim Beckman is ranked #12 in the hot seat rankings according to a nationally known website that specializes in evaluating college football coaches.
Beckman is the highest rated Big Ten coach, behind only Purdue's Darrell Hazell.
The beleaguered Illinois coach is a very disappointing 6-18 in his first two seasons coaching The Illini. Illinois was 7-6 the last two seasons of Ron Zook's tenure, including two bowl victories. Beckman has proceeded to drive that horse into the ditch.
Beckman did show improvement last season, going 4-8 after a 2-10 record in his rookie season. If Beckman doesn't deliver a minimum 6-6 record in 2014, he will most likely will be fishing in a bottomless pit somewhere with Zook.
Coacheshotseat.com has been tracking college football coaches for many years. It is viewed often by college football fans who want to see if their coach has made the rankings or moved up.


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Locating An Ethical SEO Professional
Seo, widely known as SEO, is a technique that maximizes an internet site in order to make it extremely search-engine-friendly. Search Engine Optimization can be executed at the programs as well as at the content end– the programs element of Search Engine Optimization songs the site to the demands of the most up to date search engines formulas, while the material facet of SEO includes tactically embedding desired key words in the internet site content. There are other methods too– e.g., link building, article entry as well as directory submission.
If you desire your website to register its existence in the competitive globe of Internet, you have actually got to resort to Search Engine Optimization techniques. Otherwise, a web site fails to get noticed among millions of them. However the trouble is that there are lots of unethical clothing available who assure you terrific SEO, but all they do to obtain your website a high web page ranking on the outcomes page is recruit a variety of dishonest techniques (the so called black-hat methods) to deceive the online search engine. If caught by internet search engine, your internet site could be blacklisted and prohibited for taking on dishonest SEO methods. It is, as a result, definitely vital that an internet site proprietor works in addition to a moral Search Engine Optimization consultant, as well as below's just how you have to choose one.
Overview of Selecting An Ethical SEO Professional
The Web has made the globe a smaller place and also an internet site owner can collaborate with NY Search Engine Optimization consultants based in any sort of part of the globe– there are numerous Search Engine Optimization experts' websites throughout the Net, and also tracking down one is not all that tough a job. And here's just how you should choose one:
1. If the Search Engine Optimization consultant is a specialist, after that he should be approved by numerous reputed organizations such as Google AdWords, Web Chief Executive Officer University, as well as Search Engine Optimization Pros. If the Search Engine Optimization professional has even more accreditations, well, the much more the merrier. A licensed SEO professional is moral by default– ethics are inbuilt into their job code.
2. He needs to have an excellent lineup of their clients that speak highly of him. And also he needs to not be afraid to provide a couple of references.
3. If the Search Engine Optimization expert is professional and also ethical after that it immediately follows he will have an effective performance history. So, go on and also inspect the websites he has actually done SEO on, and check if they rank high up on internet search engine results web pages.
4. The Search Engine Optimization specialist should be flexible and he should offer services such as internet site evaluation, material writing, keyword research study, link structure, SEO as well as, of course, adequate reporting back to the client.
5. The Search Engine Optimization expert should have a tidy track record, in the feeling that he have to never have actually been blacklisted for taking on dishonest Search Engine Optimization methods. Such strategies consist of spamming internet search engine, trading links with websites that belong to link farms, or masking, which means covering keywords with the exact same shade as the site's background and also stuffing a lot of them on all the web pages. You could find out if the Search Engine Optimization professional has actually turned to dubious methods by running a check on him on internet search engine and also on message boards. And also, you could constantly contact his recommendations also.
That was a little guide on how you can tackle selecting an honest SEO expert. True, locating an honest SEO specialist will take a bit of time as well as initiative, yet it is well worth it. Since an unethical Search Engine Optimization consultant could eliminate a website, while an ethical consultant could aid you create your ton of money.


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Kaari Shelf with Desk by Rowan and Erwan Bouroullec
The Kaari collection is the first collaboration between Ronan & Erwan Bouroullec and the Finnish design company Artek. The collection consists of simple shelving, a desk, a wall console and tables.
The design combines solid wood with steel banding to create a distinctive yet understated design.
Desk W200cm x 55cm
Shelves W200cm x D35cm
Total height H142 cm
Wall brackets: Natural oak with protective varnish, flat rolled steel powder coated black.
Shelf panel - black glossy melamine
Desk panel - black linoleum
Delivery8-10 weeks
view all products by Artek
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ED Magedson – Founder
Ripoff Report
e-Credit Solutions, Ron Communications, Voice Box7349 NW 34th Street, Miami, FL33122 Miami, Florida U.S.A.
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