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Publications (75)338.88 Total impact
- SourceAvailable from: PubMed Central
Article: Pigment Epithelium-Derived Factor (PEDF) Expression Induced by EGFRvIII Promotes Self-renewal and Tumor Progression of Glioma Stem Cells[Show abstract] [Hide abstract]
ABSTRACT: Epidermal growth factor receptor variant III (EGFRvIII) has been associated with glioma stemness, but the direct molecular mechanism linking the two is largely unknown. Here, we show that EGFRvIII induces the expression and secretion of pigment epithelium-derived factor (PEDF) via activation of signal transducer and activator of transcription 3 (STAT3), thereby promoting self-renewal and tumor progression of glioma stem cells (GSCs). Mechanistically, PEDF sustained GSC self-renewal by Notch1 cleavage, and the generated intracellular domain of Notch1 (NICD) induced the expression of Sox2 through interaction with its promoter region. Furthermore, a subpopulation with high levels of PEDF was capable of infiltration along corpus callosum. Inhibition of PEDF diminished GSC self-renewal and increased survival of orthotopic tumor-bearing mice. Together, these data indicate the novel role of PEDF as a key regulator of GSC and suggest clinical implications.PLoS Biology 05/2015; 13(5):e1002152. DOI:10.1371/journal.pbio.1002152 · 11.77 Impact Factor
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ABSTRACT: Interferon regulatory factor 7 (IRF7) is the master transcription factor that plays a pivotal role in the transcriptional activation of type I interferon genes in the inflammatory response. Our previous study revealed that IRF7 is an important regulator of tumor progression via the expression of inflammatory cytokines in glioma. Here, we report that IRF7 promotes glioma invasion and confers resistance to both chemotherapy and radiotherapy by inhibiting expression of argonaute 2 (AGO2), a regulator of microRNA biogenesis. We found that IRF7 and AGO2 expression levels were negatively correlated in patients with glioblastoma multiforme. Ectopic IRF7 expression led to a reduction in AGO2 expression, while depletion of IRF7 resulted in increased AGO2 expression in the LN-229 glioma cell line. In an in vitro invasion assay, IRF7 overexpression enhanced glioma cell invasion. Furthermore, reconstitution of AGO2 expression in IRF7-overexpressing cells led to decreased cell invasion, whereas the reduced invasion due to IRF7 depletion was rescued by AGO2 depletion. In addition, IRF7 induced chemoresistance and radioresistance of glioma cells by diminishing AGO2 expression. Finally, AGO2 depletion alone was sufficient to accelerate glioma cell invasion in vitro and in vivo, indicating that AGO2 regulates cancer cell invasion. Taken together, our results indicate that IRF7 promotes glioma cell invasion and both chemoresistance and radioresistance through AGO2 inhibition.Tumor Biology 02/2015; DOI:10.1007/s13277-015-3226-4 · 2.84 Impact Factor
Article: Epidermal growth factor receptor variant III renders glioma cancer cells less differentiated by JAGGED1[Show abstract] [Hide abstract]
ABSTRACT: Glioblastoma is a highly aggressive primary brain tumor in which the majority of cancer cells are undifferentiated. One of the most common oncogenic drivers for this malignancy is the epidermal growth factor receptor variant III (EGFRvIII), which lacks a portion of the extracellular ligand-binding domain due to deletion of exons 2–7 of the EGFR gene. EGFRvIII plays a critical role in tumor progression, promoting acquisition of stem cell-like features including an undifferentiated state and therapy resistance. However, the molecular mechanisms by which EGFRvIII contributes to cancer cell aggressiveness remain poorly understood. Here, we show that EGFR expression correlates with JAGGED1 expression in glioblastoma patients. Overexpression of EGFRvIII in glioma cell lines augmented JAGGED1 expression at the transcriptional level through the mitogen-activated protein kinase signaling pathway. Consequently, EGFRvIII overexpression drove partial dedifferentiation of glioma cells, as determined by tumorsphere-forming ability and expression of stem cell markers, through JAGGED1 induction. EGFRvIII-mediated radioresistance, but not chemoresistance, was also modulated by JAGGED1. Taken together, our results provide new insight into the mechanism underlying EGFRvIII-driven glioblastoma aggressiveness.Tumor Biology 12/2014; 36(4). DOI:10.1007/s13277-014-2922-9 · 2.84 Impact Factor
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ABSTRACT: Chemo-resistance and radio-resistance are a major cause of recurrence and progression of many cancers, regardless of improvements in therapies. Since cancer stem cells (CSCs) were identified as a rare population with the abilities of self-renewal; tumor initiation; aberrant differentiation, which contributes to tumor heterogeneity; and resistance to anticancer therapeutics, they have been considered a major cause of tumor recurrence post-therapy and a primary therapeutic target in relapse prevention. A number of studies have demonstrated the mechanisms underlying chemo-resistance and radio-resistance of CSCs. In this review, we describe intrinsic and extrinsic factors underlying CSC chemo-resistance and radio-resistance. The intrinsic factors regulate CSC signaling pathways involved in stem cell signaling, anti-apoptotic pathways, ABC transporter expression, and DNA damage repair systems. The extrinsic factors include the resistance mechanisms resulting from the interactions between CSCs and the microenvironment composed of vessels, fibroblasts, immune cells, extracellular matrix, and diverse soluble factors. Furthermore, we introduce diverse therapeutic agents used in experimental or clinical trials to target CSCs. Understanding how CSCs acquire resistance to anticancer therapeutics will give us opportunity to develop improved therapeutic approaches.Archives of Pharmacal Research 12/2014; 38(3). DOI:10.1007/s12272-014-0531-1 · 1.75 Impact Factor
Article: Anticancer Properties of Extracts from Opuntia humifusa Against Human Cervical Carcinoma Cells[Show abstract] [Hide abstract]
ABSTRACT: Abstract In this study, we found that the total polyphenol and ascorbic acid levels in the fruit of Opuntia humifusa are higher than those in other parts of the plant. We further hypothesized that antioxidants in O. humifusa might affect the growth or survival of cancer cells. Hexane extracts of seeds and ethyl acetate extracts of fruits and stems significantly suppressed the proliferation of HeLa cervical carcinoma cells, but did not affect the proliferation of normal human BJ fibroblasts. Additionally, the extracts of O. humifusa induced G1 phase arrest in HeLa cells. The O. humifusa extracts reduced the levels of G1 phase-associated cyclin D1, cyclin-dependent kinase 4 (Cdk4), and phosphorylated retinoblastoma proteins. Moreover, p21(WAF1/Cip1) and p53 expression significantly increased after treatment. We examined the effects of ethyl acetate extracts of O. humifusa fruit (OHF) on HeLa cells xenograft tumor growth. OHF treatment significantly reduced tumor volume and this decrease was correlated with decreased Cdk4 and cyclin D1 expression. Furthermore, flavonoids, trans Taxifolin, and dihydrokaempferol, were isolated from OHF. Thus, this extract may be a promising candidate for treating human cervical carcinoma.Journal of Medicinal Food 11/2014; 18(1). DOI:10.1089/jmf.2013.3096 · 1.70 Impact Factor
Article: Tumoral RANKL activates astrocytes that promote glioma cell invasion through cytokine signaling.[Show abstract] [Hide abstract]
ABSTRACT: The invasiveness of glioblastoma is a major cause of poor prognosis and relapse. However, the molecular mechanism controlling glioma cell invasion is poorly understood. Here, we report that receptor activator of nuclear factor kappa-B (NFκB) ligand (RANKL) promotes glioma cell invasion in vivo, but not in vitro. Unlike the invasiveness under in vitro culture conditions, in vivo xenograft studies revealed that LN229 cells expressing high endogenous RANKL generated more invasive tumors than U87MG cells expressing relatively low endogenous RANKL. Consistently, RANKL-overexpressing U87MG resulted in invasive tumors, whereas RANKL-depleted LN229 generated rarely invasive tumors. We found that the number of activated astrocytes was markedly increased in the periphery of RANKL-high invasive tumors. RANKL activated astrocytes through NFκB signaling and these astrocytes in turn secreted various factors which regulate glioma cell invasion. Among them, transforming growth factor β (TGF-β) signaling was markedly increased in glioblastoma specimens and xenograft tumors expressing high levels of RANKL. These results indicate that RANKL contributes to glioma invasion by modulating the peripheral microenvironment of the tumor, and that targeting RANKL signaling has important implications for the prevention of highly invasive glioblastoma.Cancer Letters 07/2014; DOI:10.1016/j.canlet.2014.07.034 · 5.02 Impact Factor
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ABSTRACT: The Rab protein family is composed of small GTP-binding proteins involved in intracellular vesicle trafficking. In particular, Rab3a which is one of four Rab3 proteins (a, b, c, and d isoforms) is associated with synaptic vesicle trafficking in normal brain. However, despite the elevated level of Rab3a in tumors, its role remains unclear. Here we report a tumorigenic role of Rab3a in brain tumors. Elevated level of Rab3a expression in human was confirmed in both glioma cell lines and glioblastoma multiforme patient specimens. Ectopic Rab3a expression in glioma cell lines and primary astrocytes promoted cell proliferation by increasing cyclin D1 expression, induced resistance to anti-cancer drug and irradiation, and accelerated foci formation in soft agar and tumor formation in nude mice. The overexpression of Rab3a augmented the tumorsphere-forming ability of glioma cells and p53(-/-) astrocytes and increased expression levels of various stem cell markers. Taken together, our results indicate that Rab3a is a novel oncogene involved in glioma initiation and progression.Molecular Biology Reports 06/2014; 41(9). DOI:10.1007/s11033-014-3465-2 · 1.96 Impact Factor
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ABSTRACT: Glioma initiating cells (GICs), which reside within the perivascular microenvironment to maintain self-renewal capacity, are responsible for glioblastoma initiation, progression, and recurrence. However, the molecular mechanisms controlling crosstalk between GICs and endothelial cells are poorly understood. Here we report that, in both GICs and endothelial cells, platelet derived growth factor (PDGF)-driven activation of nitric oxide (NO) synthase increases NO-dependent inhibitor of differentiation 4 (ID4) expression, which in turn promotes JAGGED1-NOTCH activity through suppression of miR-129 that specifically represses JAGGED1suppression. This signaling axis promotes tumor progression along with increased GIC self-renewal and growth of tumor vasculature in the xenograft tumors, which is dramatically suppressed by NOTCH inhibitor. ID4 levels correlate positively with NOS2, HES1, and HEY1 and negatively with miR-129 in primary GICs. Thus, targeting the PDGF-NOS-ID4-miR-129 axis and NOTCH activity in the perivascular microenvironment might serve as an efficacious therapeutic modality for glioblastoma.Cancer Research 06/2014; DOI:10.1158/0008-5472.CAN-13-1597 · 9.28 Impact Factor
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ABSTRACT: Despite current advances in multimodality therapies, such as surgery, radiotherapy, and chemotherapy, the outcome for patients with high-grade glioma remains fatal. Understanding how glioma cells resist various therapies may provide opportunities for developing new therapies. Accumulating evidence suggests that the main obstacle for successfully treating high-grade glioma is the existence of brain tumor stem cells (BTSCs), which share a number of cellular properties with adult stem cells, such as self-renewal and multipotent differentiation capabilities. Owing to their resistance to standard therapy coupled with their infiltrative nature, BTSCs are a primary cause of tumor recurrence post-therapy. Therefore, BTSCs are thought to be the main glioma cells representing a novel therapeutic target and should be eliminated to obtain successful treatment outcomes.04/2013; 1(1):9-15. DOI:10.14791/btrt.2013.1.1.9
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ABSTRACT: Cancer stem cells (CSCs) are the most aggressive cell type in many malignancies. Cell surface proteins are generally used to isolate and characterize CSCs. Therefore, the identification of CSC-specific cell surface markers is very important for the diagnosis and treatment of malignancies. We found that Nestin (a type VI intermediate filament protein), like the glioma stem cell (GSC) markers CD133 and CD15, exhibited different levels of expression in primary human glioblastoma specimens. Similar to our previous finding that cytoplasmic Nestin is expressed as a cell surface form in mouse GSCs, the cell surface form of Nestin was also expressed at different levels in human GSCs. We isolated cell surface Nestin-positive cell populations from human GSCs by fluorescence-activated cell sorting FACS analysis, and observed that these populations exhibited robust CSC properties, such as increased tumorsphere-forming ability and tumorsphere size. Mechanistically, we found that DAPT, a γ-secretase (a multi-subunit protease complex) inhibitor, reduced the proportion of cell surface Nestin-positive cells in human GSCs in a time- and dose-dependent manner, without significant changes in total Nestin expression, implying that a post-translational modification was involved in the generation of cell surface Nestin. Taken together, our data provides the first evidence that cell surface Nestin may serve as a promising GSC marker for the isolation and characterization of heterogeneous GSCs in glioblastomas.Biochemical and Biophysical Research Communications 03/2013; 433(4). DOI:10.1016/j.bbrc.2013.03.021 · 2.28 Impact Factor
Article: Early Regulation of Viral Infection Reduces Inflammation and Rescues Mx-Positive Mice from Lethal Avian Influenza Infection[Show abstract] [Hide abstract]
ABSTRACT: Differing sensitivity of influenza A viruses to antiviral effects of the Myxovirus resistance (Mx) protein implies varying global gene expression profiles in the host. The role of Mx protein during lethal avian influenza (AI) virus infection was examined using Mx1-deficient C57BL/6 (B6-Mx1(-/-)) and congenic Mx1-expressing (B6-Mx1(+/+)) mice infected with a virulent, mouse-adapted avian H5N2 Ab/Korea/ma81/07 (Av/ma81) virus. After infection, B6-Mx1(+/+) mice were completely protected from lethal AI-induced mortality, and exhibited attenuated clinical disease and reduced viral titers and pathology in the lungs, compared with B6-Mx1(-/-) mice. Transcriptional profiling of lung tissues revealed that most of the genes up-regulated after infection are involved in activation of the immune response and host defense. Notably, more abundant and sustained expression of cytokine/chemokine genes was observed up to 3 dpi in B6-Mx1(-/-) mice, and this was associated with excessive induction of cytokines and chemokines. Consequently, massive infiltration of macrophages/monocytes and granulocytes into lung resulted in severe viral pneumonia and potentially contributed to decreased survival of B6-Mx1(-/-) mice. Taken together, our data show that dysregulated gene transcriptional activity corresponded to persistent induction of cytokine/chemokines and recruitment of cytokine-producing cells that promote inflammation in B6-Mx1(-/-) mouse lungs. Thus, we provide additional evidence of the interplay of genetic, molecular, and cellular correlates governed by the Mx1 protein that critically determine disease outcome during lethal AI virus infection.American Journal Of Pathology 02/2013; 182(4). DOI:10.1016/j.ajpath.2012.12.022 · 4.60 Impact Factor
Article: Retraction notice to "Direct interaction of cellular hnRNP-F and NS1 of influenza A virus accelerates viral replication by modulation of viral transcriptional activity and host gene expression" [Virology 397 (2010) 89–99]Virology 02/2013; 436(1):245. DOI:10.1016/j.virol.2012.12.007 · 3.28 Impact Factor
Article: Blockade of EGFR signaling promotes glioma stem-like cell invasiveness by abolishing ID3-mediated inhibition of p27KIP1 and MMP3 expression[Show abstract] [Hide abstract]
ABSTRACT: Aberrant epidermal growth factor receptor (EGFR) signaling is a typical oncogenic signature in glioblastoma. Here, we show that EGFR inhibition in primary glioma stem cells (GSCs) with oncogenic EGFRvIII and EGFRvIII-transduced glioma stem-like cells promotes invasion by decreasing ID3 levels. ID3 suppresses GSC invasiveness by inhibiting p27KIP1-RhoA-dependent migration and MMP3 expression. Xenograft and human glioblastoma specimens show that ID3 localizes within glioblastoma cores, whereas p27KIP1 and MMP3 are predominantly expressed in glioma cells in invasive fronts. Together, our findings show that EGFR inhibition induces GSC invasiveness by abolishing ID3-mediated inhibition of p27KIP1 and MMP3 expression.Cancer letters 01/2013; 328(2):235–242. DOI:10.1016/j.canlet.2012.09.005 · 5.02 Impact Factor
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ABSTRACT: CD44 is generally accepted as a surrogate marker for head and neck squamous carcinoma cancer stem cells (HNSC CSCs) and only CD44+ HNSC cells have tumour initiating capacity. However, a recent report suggested that CSCs themselves might be heterogenous due to various genetic alterations. Here, we compared in vitro stem-like cell characteristics, chemoresistance and in vivo tumour formation capacity of CD44+ and CD44- HNSC cells obtained from primary HNSC patient specimens. CD44- HNSC spheroid cells generated spheroid cells again after seeding of single-dissociated spheroid CD44- HNSC cells. Immunocytochemistry assays revealed that various stem cell markers, including octamer-binding transcription factor 4 (OCT4), sex determining region Y-box 2 (SOX2) and nestin were up-regulated in CD44- spheroid cells, similar to CD44+ spheroid cells. Furthermore, CD44- spheroid cells appeared to be chemoresistant to cisplatin and showed increased levels of ABCG2, similar to CD44+ spheroid cells. Of most interest, as few as 1000 CD44- spheroid cells were able to give rise to tumours in nude mice. The collective data indicate that the cell surface marker CD44 cannot be used as a selective marker of spheroid-forming, tumour-initiating or chemoresistant cell populations, and further indicate the limitation of current HNSC CSC identification methods using the CD44 cell surface marker.European journal of cancer (Oxford, England: 1990) 07/2012; 49(1). DOI:10.1016/j.ejca.2012.06.004 · 4.82 Impact Factor
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ABSTRACT: We synthesized fluorescent capsid nanoparticles (FCNPs) by genetically inserting fluorescent protein (FP) (DsRed or eGFP) into each of 240 surface spike tips of hepatitis B virus (HBV) capsid particles. That is, when expressed in E. coli, FCNPs formed spherical nanoparticles with uniform diameter of about 40 nm owing to the self-assembly function of HBV core protein (i.e. basic assembly unit of capsid) and were successfully purified through Ni(+2) affinity- and sucrose gradient based purification. We also added the glycine-rich fexible linker peptides in between DsRed (or eGFP) and capsid to reduce fluorescence quenching among the densely displayed DsReds (or eGFPs) on the capsid surface. As compared to cognate fluorescent monomer proteins, it is notable that FCNPs showed a significantly amplified (160-170-fold) fluorescence intensity and enhanced conformational stability even in 50% serum solutin at 37 °C. The high conformational stability of FCNPs seems to result both from the highly stable structure of HBV capsid particles and from the well oriented insertion of fluorescent protein into capsid spike tip to keep native conformation of DsRed or eGFP. When estimated with continuous exposure to strong excitation light, FCNPs also showed much higher photostability than DsRed, eGFP, and a commonly used organic fluorescent dye, which happened presumably because the enhanced conformational stability of FCNPs significantly reduced photobleaching of fluorophores. Especially, it is notable that rFCNPs stably emitted high-level fluorescence inside mouse for a prolonged period, thereby showing high in vivo stability. The developed FCNPs are likely to have a great potential to be used as an effective and non-cytotoxic tool for in vivo optical imaging as well as in vitro fluorescent reporter in various biomolecular detection assays.Biomaterials 06/2012; 33(26):6194-200. DOI:10.1016/j.biomaterials.2012.05.028 · 8.31 Impact Factor
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ABSTRACT: Glioblastomas multiforme (GBM) contain highly tumorigenic, self-renewing populations of stem/initiating cells [glioblastoma stem cells (GSC)] that contribute to tumor propagation and treatment resistance. However, our knowledge of the specific signaling pathways that regulate GSCs is limited. The MET tyrosine kinase is known to stimulate the survival, proliferation, and invasion of various cancers including GBM. Here, we identified a distinct fraction of cells expressing a high level of MET in human primary GBM specimens that were preferentially localized in perivascular regions of human GBM biopsy tissues and were found to be highly clonogenic, tumorigenic, and resistant to radiation. Inhibition of MET signaling in GSCs disrupted tumor growth and invasiveness both in vitro and in vivo, suggesting that MET activation is required for GSCs. Together, our findings indicate that MET activation in GBM is a functional requisite for the cancer stem cell phenotype and a promising therapeutic target.Cancer Research 05/2012; 72(15):3828-38. DOI:10.1158/0008-5472.CAN-11-3760 · 9.28 Impact Factor
Article: Interferon regulatory factor 7 regulates glioma stem cells via interleukin-6 and Notch signalling.[Show abstract] [Hide abstract]
ABSTRACT: Inflammatory microenvironment signalling plays a crucial role in tumour progression (i.e. cancer cell proliferation, survival, angiogenesis and metastasis) in many types of human malignancies. However, the role of inflammation in brain tumour pathology remains poorly understood. Here, we report that interferon regulatory factor 7 is a crucial regulator of brain tumour progression and heterogeneity. Ectopic expression of interferon regulatory factor 7 in glioma cells promotes tumorigenicity, angiogenesis, microglia recruitment and cancer stemness in vivo and in vitro through induction of interleukin 6, C-X-C motif chemokine 1 and C-C motif chemokine 2. In particular, interferon regulatory factor 7-driven interleukin 6 plays a pivotal role in maintaining glioma stem cell properties via Janus kinase/signal transducer and activator of transcription-mediated activation of Jagged-Notch signalling in glioma cells and glioma stem cells derived from glioma patients. Accordingly, the short hairpin RNA-mediated depletion of interferon regulatory factor 7 in glioma stem cells markedly suppressed interleukin 6-Janus kinase/signal transducer and activator of transcription-mediated Jagged-Notch-signalling pathway, leading to decreases in glioma stem cell marker expression, tumoursphere-forming ability, and tumorigenicity. Furthermore, in a mouse model of wound healing, depletion of interferon regulatory factor 7 suppressed tumour progression and decreased cellular heterogeneity. Finally, interferon regulatory factor 7 was overexpressed in patients with high-grade gliomas, suggesting its potential as an independent prognostic marker for glioma progression. Taken together, our findings indicate that interferon regulatory factor 7-mediated inflammatory signalling acts as a major driver of brain tumour progression and cellular heterogeneity via induction of glioma stem cell genesis and angiogenesis.Brain 03/2012; 135(Pt 4):1055-69. DOI:10.1093/brain/aws028 · 10.23 Impact Factor
Article: Cellular characteristics of head and neck cancer stem cells in type IV collagen-coated adherent cultures[Show abstract] [Hide abstract]
ABSTRACT: Although head and neck squamous carcinoma cancer stem cells (HNSC-CSCs) can be enriched in serum-free suspension cultures, it is difficult to stably expand HNSC-CSC lines in suspension due to spontaneous apoptosis and differentiation. Here, we investigated whether HNSC-CSCs can be expanded without loss of stem cell properties by adherent culture methods. Cell culture plates were coated with type IV collagen, laminin, or fibronectin. We examined cancer stem cell traits of adherent HNSC-CSCs grown on these plates using immunocytochemistry for stem cell marker expression and analyses of chemo-resistance and xenograft tumorigenicity. We also assessed the growth rate, apoptosis rate, and gene transduction efficiency of adherent and suspended HNSC-CSCs. HNSC-CSCs grew much faster on type IV collagen-coated plates than in suspension. Adherent HNSC-CSCs expressed putative stem cell markers (OCT4 and CD44) and were chemo-resistant to various cytotoxic drugs (cisplatin, fluorouracil, paclitaxel, and docetaxel). Adherent HNSC-CSCs at the limiting dilution (1000 cells) produced tumors in nude mice. Adherent HNSC-CSCs also showed less spontaneous apoptotic cell death and were more competent to lentiviral transduction than suspended HNSC-CSCs. In conclusion, compared to suspension cultures, adherence on type IV collagen-coated culture plates provides better experimental conditions for HNSC-CSC expansion, which should facilitate various refined cellular studies.Experimental Cell Research 03/2012; 318(10):1104-11. DOI:10.1016/j.yexcr.2012.02.038 · 3.37 Impact Factor
Article: EGFR-AKT-Smad Signaling Promotes Formation of Glioma Stem-like Cells and Tumor Angiogenesis by ID3-Driven Cytokine Induction[Show abstract] [Hide abstract]
ABSTRACT: Aberrant activation of receptor tyrosine kinases (RTK) is causally linked to the pathobiological traits of glioblastoma and genesis of glioma stem-like cells (GSC), but the underlying mechanism is still unknown. Here, we show that epidermal growth factor receptor (EGFR) signaling regulates the proliferation, angiogenesis, and acquisition of GSC characteristics by inducing inhibitor of differentiation 3 (ID3) and ID3-regulated cytokines [GRO1 and interleukins (IL)-6 and 8] induction. We found that EGFR-mediated ID3 expression was regulated by Smad5, which was directly phosphorylated by AKT. Furthermore, ID3 alone imparted GSC features to primary astrocytes derived from Ink4a/Arf-deficient mouse, and EGFR-ID3-IL-6 signaling axis gave rise to tumor cell heterogeneity. Conversely, EGFR inhibitors suppressed EGFR-AKT-Smad5-driven induction of ID3, which led to a decrease in the tumorsphere forming ability of GSCs and U87MG cells that possess an active mutant EGFR, EGFRvIII, without obvious cytotoxic effects. However, these cells seemed to regain colonogenic ability after removal of the EGFR inhibitors. Together, the results delineate a novel integrative molecular mechanism in which the RTK-ID signaling pathway governs genesis and maintenance of GBM histopathologic features, such as GSCs-based tumor initiation, progression, and angiogenesis.Cancer Research 11/2011; 71(22):7125-34. DOI:10.1158/0008-5472.CAN-11-1330 · 9.28 Impact Factor
Article: Identification of a peptide that interacts with Nestin protein expressed in brain cancer stem cells[Show abstract] [Hide abstract]
ABSTRACT: Glioma stem cells (GSCs) are presumably major culprits for brain tumor initiation, progression, and recurrence after conventional therapies. Thus, selective targeting and eradication of GSCs may provide a promising and effective therapeutic approach. Here, we isolated a GSC-targeting (GSCT) peptide that demonstrated selective binding affinity for many undifferentiated GSCs using in vitro phage display technology. This GSCT peptide binds to isotypes of Nestin proteins specifically expressed in GSCs, enabling it to target Nestin-positive cells in human glioblastoma tissues. In human glioblastoma tissue specimens, the fluorescence-conjugated GSCT peptide could visualize putative GSC populations, showing its possible use as a diagnostic agent. GSCT peptide is also internalized into undifferentiated GSCs specifically in vitro, and moreover, intravenously injected GSCT peptide effectively penetrated into tissues, specifically accumulated in gliomas that arise from subcutaneous and orthotopic implantation, and predominantly targeted Nestin-positive cells in these tumors. Thus, our GSCT peptide may be useful for the development of more promising therapeutic and diagnostic modalities that target GSCs in brain tumors.Biomaterials 08/2011; 32(33):8518-28. DOI:10.1016/j.biomaterials.2011.07.048 · 8.31 Impact Factor
Top Journals
Korea University
Sŏul, Seoul, South Korea
- • Department of Biotechnology
- • Department of Food Bioscience and Technology
St. Jude Children's Research Hospital
Memphis, Tennessee, United States
- Department of Infectious Diseases
Sungkyunkwan University
Sŏul, Seoul, South Korea
- Department of Neurosurgery
Harvard UniversityCambridge, Massachusetts, United States
Chungbuk National University
Tyundyu, North Chungcheong, South Korea
- College of Medicine and Medical Research Institute
Dana-Farber Cancer Institute
Boston, Massachusetts, United States
- Department of Medical Oncology
Harvard Medical SchoolBoston, Massachusetts, United States
University of Minnesota DuluthDuluth, Minnesota, United States
Seoul National University
Sŏul, Seoul, South Korea
- Department of Agricultural Biotechnology


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Floor Plans & Pricing
Does your furniture fit? Pick a floor plan below and design your new place!
General Directions
From I-5N, exit at SR-500 to Andresen. Turn right onto Andresen. Left on 4th Plain. We will be on your right hand side in about .5 miles. From I-205N, Take exit 30 towards SR WA-500 W. Merge onto SR WA-500 W. Take the Westfield Mall exit. Turn left on Thurston. Take a Right onto 4th Plain Blvd and we'll be on the left side (next to Vancouver Christian High School).
Apartment Features
- Balcony
- Cable Ready
- Ceiling Fan(s)
- Dishwasher
- Fireplace
- Smoke Free
- Washer & Dryer Connections
Community Features
- Covered Parking
- Extra Storage
- Garage
- Laundry Facility
- Public Transportation
- Pet Friendly
Special Features
- Pets
- Pets AcceptedWeight restriction: 50Deposit: 250Breed restriction - call for details
Additional Features
- Unique floor plans, expansive in size
- Apartments include 1 reserved covered space
- Smoke-free Community!
- Extra storage!
- Spacious patios, covered
- Washer/dryer hook-ups
- Washers/dryers available! Ask for details.
- Pet friendly community
- Woodburning fireplaces
- Storage off patios and balconies
- Adjacent to park
- On-site day care / pre-school
- Close to public transit
- Conveniently located near Westfield Mall
- Close to Vancouver Plaza
- RV parking for a monthly fee
- 2nd floor apartment homes, covered balconies
- Vaulted ceilings on all top floor apartments
Van Plaza Apartments
Welcome home to Van Plaza! We invite you to enter a new version of coming home...an atmosphere of comfort and convenience that will surpass your expectations. Van Plaza features a variety of living options while offering a superb central location. With close proximity to freeways and public transportation options, you will save valuable time daily. Shopping centers, theaters, malls and restaurants are all just moments away from home, allowing you more time to spend enjoying family, friends and leisure. Come home to Van Plaza... where comfort and convenience are paramount!
Check Availability or call: (360) 718-9246 (888) 717-9389 (360) 524-9897
Community Information
Community Characteristics
Community Profile
- Population
- 34,091
- Growth Since 2000
- 40.92%
- Population Density
- 2648
- Male
- 48%
- Female
- 52%
Household Income
- Median
- $56,065
- Average
- $64,324
Office Hours
|Move-in Ready Tours available on weekends by appointment
|10:00 AM to 05:00 PM
|10:00 AM to 05:00 PM
|10:00 AM to 05:00 PM
|10:00 AM to 05:00 PM
|10:00 AM to 05:00 PM
|Appointments available after hours
Lease Terms
6-Month, 9-Month, 12-Month
Check Availability or call:(360) 718-9246 (888) 717-9389 (360) 524-9897
Fax: 3602569879
Visit the property's management website

subset: commoncrawl


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STAY TUNED: Discovery debuts 'Skunk Ape' series; speed-walking with WINK
After Tuesday, Southwest Florida may be forever changed in the eyes of the world.
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6 posts tagged with exhibit by Brandon Blatcher.
Displaying 1 through 6 of 6.
An interactive paper sculpture
"Every time the paper blade falls a camera will be triggered to capture the expression of the those who have put their neck on the line for an art experience like no other. Each fearful facial expression, forever immortalized on the PaperCuts-Exhibtion.com."
Ball sucking done right
The boundaries separating humans and animals disappears
Sweet transformations, as art
"I like the physical nature of building the sculpture"
She connected the discarded organ replacement machines together and had them 'breathe' in closed circuits. The machines of The Immortal keep each other alive through circulation of electrical impulses, oxygen and artificial blood.
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Entries in 'Yamaha' (138)
SPECIAL FOCUS: Is the acoustic market still king?NEWS
For many general MI retailers, the acoustic guitar market is considered the most dependable sector in an ever-challenging economic climate. But is this still the case? MI Pro talks to ...
COUNTDOWN TO MIRC: Yamaha to shine a light on Line 6NEWS
Yamaha is returning to MIRC this year with the recently acquired Line 6 brand, where upon it will look to present its expansive product range to dealers.
Yamaha produces short film to inspire young musiciansNEWS
Celebrating the career of the London Symphony Orchestra's youngest player, Peter Moore, Yamaha has produced a short film designed to inform and inspire other young musicians.
Yamaha announces Mark Mondesir drum clinicsNEWS
Yamaha Music Europe has announced a series of drum clinics with Yamaha Drums artist, Mark Mondesir.
TC Electronic and Yamaha announce one-off Nathan East clinicNEWS
TC Electronic and Yamaha have collaborated on a high-profile clinic session featuring Grammy nominated musician Nathan East, in association with Guilford's Andertons Music on Tuesday, May 19th.
Ronnie Scott's chooses Yamaha for house drumsNEWS
Yamaha Drums UK has announced that Ronnie Scott's Jazz Club has chosen the company for its house drums.
Musikmesse 2015 in reviewNEWS
Musikemesse has closed its doors for another year, and the international MI community has returned home after announcing their latest products and developments. No doubt you will have heard of ...
Simon Edgoose embarks on DTX demo tour with YamahaNEWS
Yamaha has announced a series of events demonstrating its DTX electronic drum kits and showcasing its new products for 2015.
New president for Yamaha Music EuropeNEWS
Yamaha has appointed Thomas Schoepe as its new European president.
INTERVIEW: Yamaha's Darren Power on the firm's Line 6 partnershipNEWS
Having announced its acquisition of Line 6 in January, Yamaha's distribution partnership with the US brand is now in full swing. Daniel Gumble caught up with Yamaha pro music director, ...
Yamaha and Jazz FM launch Replay Project for lapsed musiciansNEWS
Yamaha and Jazz FM have teamed up to launch the Replay Project, which aims to get lapsed musicians playing again by placing them centre-stage at a UK festival alongside the ...
TOP 10: This week's most read storiesNEWS
As another week comes to an end, we take a look at the most read stories of the past seven days.
Yamaha Music London announces in-store events programmeNEWS
The newly refurbished Yamaha Music London store has announced it will be getting behind this year's National Learn to Play Day, along with many other in-store events.
Francesco Tristano joins YamahaNEWS
Musician and composer Francesco Tristano has been named as the latest artist to receive the official Yamaha artist status.
MIRC 2015: Yamaha including Line 6 confirmed as key partnerNEWS
Yamaha including Line 6 has been confirmed as a key partner for this year's MIRC, which returns to Northampton's Whittlebury Hall on Wednesday, June 17th.
TOP 10: This week's most read storiesNEWS
As the first week of February comes to an end we take a look at the most read stories of the past seven days.
Yamaha cuts the ribbon on refurbished London storeNEWS
Last night saw Yamaha cut the ribbon on its refurbished London store.
NAMM 2015: Line 6 and Yamaha collaborate on new guitarNEWS
Line 6 has revealed the latest in its Variax series with the introduction of the Variax Standard guitar.
Win one of 20 Pianos with Yamaha and Emeli SandeNEWS
Yamaha and Emeli Sande are giving local good causes the chance to win one of 20 Yamaha pianos as part of Emeli Sande's Community Clavinova campaign.
Line 6 to be distributed by Yamaha as of AprilNEWS
Line 6 is to be distributed through Yamaha Music Europe, effective April 1st, 2015.
Yamaha reveals UK and Ireland brass and woodwind scholarship finalistsNEWS
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The Walt Disney Company and Yamaha Music Europe (UK) have teamed up to inspire the next generation of young musicians with the Have a Go at Let it Go national ...
INTERVIEW: Mark Rolfe, Yamaha UK MDNEWS
In the 18 months since his arrival as its new UK boss, Yamaha's Mark Rolfe has overseen a rapid rate of change, with divisional restructuring and an overhaul of its ...
Yamaha Music London to host Bösendorfer design eventNEWS
Yamaha Music London is to host a special event on December 3rd, at which the Bösendorfer bespoke concept grand piano, EDGE, will be presented by its designers.


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Tag: gardens by the bay
Urban Adventure at Gardens by the Bay, Singaporewritten by scrabbyknees on 2012-08-13 in #world #locations
Gardens by the Bay is a newly-opened attraction on the bayfront of Singapore that boasts of beautiful flora and fauna and spectacular light shows. Located in the heart of Singapore's new downtown Marina Bay, next to the Marina Reservoir, Gardens by the Bay has three distinct waterfront gardens – Bay South Garden, Bay East Garden, and Bay Central Garden. It spans 101 hectares and was originally built to enhance the greenery and flora in Singapore.3 10 Share Tweet
The "Building of the Year" is From Singaporewritten by soundfoodaround on 2012-10-08 in #news
The World Architecture Festival took place on the shores of Singapore last week, at the Marina Bay Sands. It was a venue to be inspired at. The two peaked domes that stood out on the horizon - the Cooled Conservatories - couldn't help but be noticed owing to their design and function. It's no wonder it took home the World Building of the Year!4 Share Tweet
ReeLocations: Singapore's Wonderland - Gardens By The Baywritten by an_lai_drew on 2013-05-15 in #world #locations
Gardens by the Bay is undoubtedly one of the most wonderful places in Singapore. With its unique structure, the Gardens promote itself as an attractive place to be visited on the popular Marina Bay.2 Share Tweet


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Singh Is Kinng is undoubtedly one of the most eagerly awaited releases of 2008 and as its release date (Aug 8th) is drawing closer, its director Anees Bazmee is understandably excited about his project. In a brief chat with him, he told us why his film promises to be something that Bollywood has never witnessed before.
Presently the most in demand director of Bollywood, Bazmee with two back to back super hits, No Entry and Welcome tells us, "SIK has all the right masala of a good commercial venture. It features terrific music, mind-blowing action sequences shot in virgin locales of Egypt, Punjab and Gold Coast in Australia apart from the uniqueness of most of the film's actors sporting a turban, which is a first for any Hindi film!"
So was Akshay always his first choice for the title role? Or was he wanting to cash in on his Welcome hit jodi? "Whenever I start writing any of my script, the first thing that I decide upon is the name of my hero's character. The character of Singh in SIK is that of a very happy go lucky guy who is a dare devil, knows no fear and is not a manipulative person at all. He just loves to eat, dance and live life King size but for that he believes in working very hard. That is when I decided to name him Happy Singh. Akshay I thought then was my perfect choice for the role."
How was the look of Akshay finalized? "After I decided to cast Akshay for the lead role, the very next day I spoke to Akshay's designer friend Shabina Khan for deciding upon Akshay's look. I was confident that Akshay would look great in a turban. That time rather than a complete Sardar with beard and turban, I told Shabina to design just a turban just to see how it looks on him. She came back with a turban and we tried it on Akshay and he looked amazing in it. I then took some pictures from my mobile just to get other's views too and everyone loved it. That's how we decided his look".
So has Akshay lived up to his expectations? "Yes of course! Akshay has done complete justice to the role and my confidence in him. He has many actions never attempted on Hindi screen before there is sky diving, jumping from one lift to another. He enjoys the thrill and he was very excited performing them because he was action after a real long time. Katrina also has improved as an actress and is very hard working. Every character in the film has a definite role no one has been wasted including Sonu Sood, Ranvir Shorey and Javed Jaffrey."
How does it feel to be the most sought after filmmaker whose movies spell huge box office returns? "See, I am not involved with the business aspect of the film. I want my films to do well and I am not doing films to promote myself. If I am not excited about my script I will just not do the film. I want my actors to do well as well. Ultimately, the audience should enjoy the film. I also don't believe in camps either. I only like to work with people whom I am comfortable with."
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|User Rating
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I am sooooo waiting for this movie....it looks great...i can hardly wait...
OMG..i am literally diieng to watch this movie..and wots more is that its releasing on my birthday n i paln to watch it first day first show..i trully love akki-kats jodi and cant wait for this one..the songs are fab too!
x Mrs.KaranSinghGrover x
m dying to see some gr88 Akkikat romance.m sure it will prove the biggest hit of this year.
Cant wait for this!!
thanx for the article!
yay for akshay!!!!! i sooo wanna watch this movie first day first show...but it's releasing on thurs and i have uni...whilst im willin to skip, i know noone else is that obsessed! LoL
i dying to watch htis film..
love akshay as a punjabi munda!!
after all punjabian dee shaan vakhri!!!
m surely looking forward to it..
it will surely rock!!
r waiting for it...thnks
yeah! baby! AkII is gonna rockkk..
Jee karda is already a hit song!!
Its gonna be a SUPERR hittt!!!!!!
Waiting for its release...august 8!!!
A world without Doctors would be a pain. Literally! Doctors are an ... 440
Sanjit Bedi who was recently in Jane Kya Baat Hui has passed away ... 196
Actor-filmmaker Kamal Haasan wants to watch "Gour Hari Dastaan - The ...
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New Mexico suspect arrested in Waterloo
On April 23rd, 2015 the Waterloo Police Department received notification from the Bernalillo County Sheriffs Department in Albuquerque, New Mexico that they had an active warrant on a charge of attempted murder for Deandre Marquis Stanford, age 18. Waterloo Police located Stanford at his residence, 337 Monroe Street. He was taken into custody without incident. Stanford was transported to the Black Hawk County Jail where he is awaiting extradition back to New Mexico.
Captain Dave MohlisInvestigations Division


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Dr. Carlo Z. Biscaro, MD
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- 3816 Woodruff Ave Ste 100
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- 2 Locations
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Dr. Carlo Z. Biscaro graduated from the Georgetown University School of Medicine in 1964. He works in Long Beach, CA and 1 other location and specializes in Orthopaedic Surgery and Orthopedic Sports Medicine. Dr. Biscaro is affiliated with Chapman Medical Center, Fountain Valley Regional Hospital & Medical Center and Western Medical Center Santa Ana.
Orthopaedic Surgery, Orthopedic Sports Medicine
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Peek in profiq!
Posted 2 weeks ago by Petra
On a warm sunny day of March 19th there was a scent of anticipation at the office. We held an Open Day at profiq. Everybody was getting ready for the afternoon guests. How many will come? Will they be interested in our work? Will they enjoy chatting with us? Are we going to show and […]
Read article or visit Blog Archive


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Securities and Exchange Commission: Family Offices
GAO-11-816R: Jul 14, 2011
Additional Materials:
- Full Report:
Shirley A. Jones
(202) 512-8156
(202) 512-4800
(202) 512-8156
Office of Public Affairs
(202) 512-4800
GAO reviewed the Securities and Exchange Commission's (SEC) new rule on family offices. GAO found that (1) the Investment Advisers Act of 1940 imposes certain registration and other regulatory requirements on investment advisers. The Dodd-Frank Wall Street Reform and Consumer Protection Act of 2010 excluded family offices from the definition of investment advisers. This final rule defines family offices for the purposes of that exclusion; and (2) SEC complied with applicable requirements in promulgating the rule.
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YIELD: Serves 6
Preheat oven to 350°F. Lightly butter baking pan. Combine crumbs, walnuts, 4 tablespoons butter, corn syrup and salt in small bowl. Loosen skin of each breast half. Stuff 1/6 of crumb mixture (about 1/4 cup) under skin of each. Secure skin with toothpick, enclosing stuffing. Season with salt and pepper.
Heat 2 tablespoons butter in heavy large skillet over high heat. Add chicken to skillet and sauté until brown, about 3 minutes per side. Arrange chicken in prepared baking pan.
Blend crushed pineapple and reserved 2 tablespoons juices, orange juice concentrate, bourbon and remaining 2 tablespoons butter in small bowl. Spoon mixture over chicken.
Bake chicken until cooked through, about 35 minutes. Transfer chicken to platter. Spoon pan juices over. Garnish chicken with orange wedges and banana slices, if desired.


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I enjoy cycling and traveling. I find bicycles sexy, and women who ride bicycles even sexier.
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Should I upgrade to Windows 10? 8 reasons why you should upgrade to Windows 10... and 2 why you…
Small SSD boot drive bargain.
KRONOS the First 05 Sep 12
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Shopping. Rediff.com - Non delivery/ no response
321 Reviews
B Selvam
I Had purchased a PANASONIC NV-GS85 DIGITAL from rediff shopping on 18 Dec 2007 and the amount debited from my credit card on 20 dec 2007, I was informed by rediffmail that my item is despatched details as follows
PANASONIC NV-GS85 DIGITAL CCD CAMCORDER Sandeep Vig (Big Baazaar) Aramex 875341756 27-12-2007 http://www.aramexindia.com Expected delivery: You should receive your order between 31 Dec, 2007 and 04 Jan, 2008.
But till todate i havenot received the item even after approaching rediff customer care they have not given any correct details, the courier detail given by rediff shpopping turned out to be invaild, indicating that i have been cheated by rediff shopping. Kindly help me to proceed legally against this web site, to retreive my money.
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"My mission is to be the ray of hope, the guy who stands out there on that beautiful field and owns up to his mistakes and lets people know it's never completely hopeless, no matter how bad it seems at the time. I have a platform and a message, and now I go to bed at night, sober and happy, praying I can be a good messenger." -Josh Hamilton
"My mission is to be the ray of hope, the guy who stands out there on that beautiful field and owns up to his mistakes and lets people know it's never completely hopeless, no matter how bad it seems at the time. I have a platform and a message, and now I go to bed at night, sober and happy, praying I can be a good messenger." -Josh Hamilton
I put Seaver on that list because, IMO, he was likely the greatest pitcher the game had seen from the time Lefty Grove retired until the time Roger Clemens and Greg Maddux came up (and depending on how you rank Clemens now due to his "other" circumstances opens up another can of worms). That's a period of 40-50 years right there; that's impressive, yet few people likely realize it. Unfortunately, guys like Koufax, Gibson, Ryan, etc. seem to get more recognition than Seaver, yet Seaver was simply a greater pitcher than those guys. Spahn may have an argument over Seaver, but I'd still take Seaver.
Kevin Gregg and Jason Marquis brought back vivid memories of the Lost Decade.
Kevin Gregg: DFA'd May 11, 2015
Jason Marquis: DFA'd June 5, 2015
Yet others have noted, I do dislike the idea that Suzuki can do absolutely anything he wants to offensively. He can't. He won't walk and basically feels that doing so is a waste of his time. And yet, it's really not his choice. He just can't do it, which is another pretty severe limitation for someone who's supposed to be able to do anything he wants.
I have absolutely no complaints about his glove or baserunning however.
Let's see...what else...
Oh, he churned an international hype machine into an MVP award over at least one more deserving teammate in 2001. Then there's my own pet peeve..."Ichiro" on the back of the jersey. If any other MLB player did that he'd get fined. It's not a cultural item. He uses his first name to get more attention. Regardless of what he got away with in Japan, I've always felt that taking the field for his first MLB game with his first name on the back of his jersey demonstrated a profound lack of respect for the game. It annoys me to no end and I refuse to use only Suzuki's first name in any discussion.
Suzuki is an excellent player and he's fun to watch. It's just that he hasn't, for me, ever lived up to his hype.
"The problem with strikeouts isn't that they hurt your team, it's that they hurt your feelings..." --Rob Neyer
"The single most important thing for a hitter is to get a good pitch to hit. A good hitter can hit a pitch thats over the plate three times better than a great hitter with a ball in a tough spot.
--Ted Williams
Overrated - 50's baseball History - NYC centric to the core, even to today, Costas, Crystal.... YAWN.... I'm tired of the press that still comes out of that era, one big love fest of a bygone era.
Underrated - 70's Baseball History - Bullpen carts with hats, ugly uniforms, plastic grass and the San Diego Chicken... and that's just touching the items not playing the game.
For those who believe, no proof is necessary. For those who don't believe, no proof is possible
Scarily enough, I think Albert Pujols may be underrated, even though he's acknowledged as the best player in the NL. Let's put it this way: He's at least 95% of the player A-Rod is; is he 95% as well-known?
"In baseball, you don't know nothin'"...Yogi Berra
"Reality tells us there are no guarantees. Except that some day Jon Lester will be on that list of 100-game winners." - Peter Gammons
1. Joe DiMaggio (878) *
2. Jimmie Foxx (875) *
3. Ken Griffey (874)
4. Frank Robinson (871) *
5. Hank Aaron (864) *
There's "best guy in the league right now" and then there's "on pace for one of the greatest careers of all-time". Those are hardly the same thing.
I haven't seen anybody mention Ron Santo yet. He's there with Blyleven in my book as the biggest HoF snubs.
Another guy who simply doesn't get the props he deserves is Frank Thomas. Yes, I know he has zero defensive value, but wow, was he an amazing hitter. Take a look at his 1994 season: .353/.487/.729. For his career, .300+ BA, 500+ HR, and more BBs than Ks. Just wow.
Games are won on run differential -- scoring more than your opponent. Runs are runs, scored or prevented they all count the same. Worry about scoring more and allowing fewer, not which positions contribute to which side of the equation or how "consistent" you are at your current level of performance.
Board Moderators may, at their discretion and judgment, delete and/or edit any messages that violate any of the following guidelines: 1. Explicit references to alleged illegal or unlawful acts. 2. Graphic sexual descriptions. 3. Racial or ethnic slurs. 4. Use of edgy language (including masked profanity). 5. Direct personal attacks, flames, fights, trolling, baiting, name-calling, general nuisance, excessive player criticism or anything along those lines. 6. Posting spam. 7. Each person may have only one user account. It is fine to be critical here - that's what this board is for. But let's not beat a subject or a player to death, please.


text:
See other Seoul properties
Bong House
1st floor, 117-2, Myeungryun-3ga, Myeungryun-Dong, Jongro-Gu, Seoul, South Korea, Distance from city centre: 2.6km
Real Reviews
Real reviews from fellow travellers
These are trusted reviews from guests who have actually stayed here. We hope you find them helpful.
Note: we only give a property a rating once it has received a minimum of 3 reviews.
- Page:1/1
- " Over all, the room was okay. Beds are clean, staff is super friendly. Uncomfortable: Street noise, a bar next to my window and no ventilation in the bathroom. (There was a window, but it was blocked because the shower curtain was mounted against it). I think this might be the reason why hundreds of small flies lived there and in the whole room. My door's security passcode matched the passcode for a public door that everyone gets told about on checkin, this should definately be changed. "
- 24 Apr 2015 Peter Germany
- " Very nice place, nice location, value for money, very helpful staff. "
- 21 Apr 2015 Anonymous India
- " Security was bad, noise was not controlled, toilets were not clean, did not even get a reply from the hostel when I told them my things were stolen. "
- 09 Apr 2015 Anonymous Singapore
- " The Bong House's promotional deals are the best we encountered in our travels across South Korea. It was about 10,000 won per night. The facilities are adequate but are well maintained by the industrious staff. It's location in Hyehwha is very convenient and provides quick access to GS 25 / Lotte / CU marts, cinemas, theatres, restaurants and a subway line "
- 02 Jan 2015 Tharindu New Zealand


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Calif. Legislature under pressure over secrecy
Many staffers see no need to deviate from the longstanding policy. The Assembly Rules Committee has not previously released detailed budget documents, said its chief administrative officer, Jon Waldie, earlier this month.
"The LORA's been in effect since 1975. You guys have been getting the same response from us since then," he said.
Portantino, who plans to run for Congress next year in a Southern California district, has used the attention over his dustup with the speaker to his own advantage. He is now proposing scrapping the Legislature's exclusive disclosure law and making it subject to the California Public Records Act - a proposal that is unlikely to go far.
"It's time for no more gimmicks, no more tricks. Let's embrace transparency," Portantino said. "The only thing we need to do that is the moral will."
The Associated Press


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Could a cure for the common cold be in sight? Scientists find compound that stops viruses infecting humans
- They found a compound that stops the virus responsible for hand, foot and mouth disease breaking open and releasing viral RNA into human cells
- This means it makes the virus is unable to infect people
- They believe the drug could also be effective against the cold virus
- So far, the compound has only been tested on isolated cells
Scientists have created a new compound which they say could offer a cure for the common cold
A cure for the common cold could be a step closer, new research suggests.
Scientists believe they have found a drug which could eventually be used to combat the viruses that cause colds.
They say they have developed a compound which could prevent the viruses infecting humans.
The researchers, from Oxford, Leeds, Beijing, and Innsbruck have found a compound which targets the virus responsible for hand, foot and mouth disease – a condition that causes epidemics in children in Asia.
This, they say, is also an important breakthrough in the hunt for a cure for the common cold.
This is because the drug could also be effective against viruses similar to those that cause hand, foot and mouth disease – including the common cold virus.
Professor Dave Stuart, Director of the Division of Structural Biology (STRUBI) in the Nuffield Department of Medicine at the University of Oxford, said: 'By targeting a structural feature also found in related viruses, it should be possible to devise similar therapeutics to target them.
'Within the field, I am aware of one company that is already making progress in targeting the major common cold virus. Our work is still at an early stage, but we are working with academic groups in China to take the inhibitor forward.'
The new drug treatment, which so far has been tested only in isolated cells, was created using pionerring techniques.
The researchers focused on finding a drug that could target the structure of the virus.
Firstly, they had to understand the structure of the virus. Secondly, they determined how that structure related to the functioning of the pathogen.
Finally, they developed a means of interacting with that structure to disable the virus.
The structure of EV71 – the virus that causes hand, foot and mouth disease - was first solved in 2012.
The researchers say the compound can prevent viruses breaking open and releasing viral RNA into human cells - this makes them unable to infect people. Image shows the common cold virus
After this, scientists used a giant microscope to determine how the virus changes shape to enter human cells.
Called Diamond Light Source, this giant microscope allows scientists to glimpse the shape of virus and bacteria components at atomic-level and get some insight into how they function.
The virus has an outer shell which, once inside a host cell, breaks apart releasing the viral RNA into the cell.
The team discovered a very potent molecule which disables the mechanism by which the viral shell breaks open, thus stopping the virus in its tracks by making it unable to infect the person.
When they determined the virus structure in 2012, the team saw a small pocket inside the virus where a drug might fit.
The compound has currently only been tested on isolated cells so a drug for use by people is still a long way off
They have now developed a potential drug molecule that can sit inside this pocket, where it locks the virus rigid, preventing it breaking open and releasing its RNA.
However, this research is still in its early stages, and there is a long way to go before the drug treatment is available on the market.
The researchers say they also have to be cautious as viruses evolve exceptionally fast, and it may be that EV71 mutates to overcome the inhibitor.
However, the early signs are promising, and now that the methodology exists, scientists may be able to develop the inhibitor to become resistant to mutations.
The research was published in the journal Nature Structural and Molecular Biology.
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What about if the logo was simply the type? Any thoughts? I like the graphic in the background (top left of the previous shot) too and it could be incorporated subtly throughout the identity...?
More Owen Jones
keyboard shortcuts: ← previous shot → next shot L or F like Z toggle zoom


text:
I have scatterplot of data (x and y values). I want to calculate the weighted average and standard deviation as a function of X. For each one of my points I then want to calculate the number of standard deviations away each value is from the predicted. I am currently using the loess.sd function from the 'msir' package since it calculates the sd for me. Does anyone know how I can get the predicted sd for each data point? Or perhaps there is an alternative or better way to address this calculation? Thanks in advance.
My current code:
#... scatter plot of data
#loess +- 1 sd
std_loess = loess.sd(xy, nsigma =1,span=0.3)
# ... add weighted average to plot
# .... add weighted sd to plot
#.... get observed data points
# ... get expected value for each data point
obs = xy[,2]
# ... get predicted sd for each data point
expected = predict(std_loess$model,data.frame(xy))
# ...get predicted sd for each data point
exp_sd = ??????????????????
# ...get predicted sd for each data point
sd_away = (obs - expected) / exp_sd


text:
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text:
Recipe by: Vanias
Original recipe yields 12 servings
Amount per serving ({{servings}} total)
Based on a 2,000 calorie diet
Sort stores by
Ready In
See how to make a scrumptious, berry-filled, no-bake cheesecake.
This impressive cake is rich with the flavor of real strawberries.
Your rating
The boys loved it.. the finished it in one day!! Fun to make. Great to eat
I must say this is the worst recipe ever. The egg smell is a total put off and the sugar is waay too much.


text:
Originally written on 60 Max Power O | Last updated 3/28/13
The Pittsburgh Steelers are starting to come out of their shell. After trimming the roster through cuts and restructuring tons of contracts, the team can finally focus on some needs via free agency. The biggest need is at running back and a healthy Ahmad Bradshaw would give the Steelers a huge boost. Bradshaw is exactly what the doctor ordered, a tough runner who can be a strong leader in the clubhouse. According to Dan Hanzus of NFL.com, if Bradshaw can pass a physical, the Steelers will sign him. Hanzus writes: 'NFL.com's Aditi Kinkhabwala reported that Bradshaw is getting a physical from Pittsburgh Steelers doctors on Thursday. If everything checks out -- which is no certainty -- Pittsburgh will make an attempt to sign the free-agent running back, according to a source apprised of the visit.' var switchTo5x=true; stLight.options({publisher:''});
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