Sample records for anchorage independent growth

  1. Reductive carboxylation supports redox homeostasis during anchorage-independent growth. (United States)

    Jiang, Lei; Shestov, Alexander A; Swain, Pamela; Yang, Chendong; Parker, Seth J; Wang, Qiong A; Terada, Lance S; Adams, Nicholas D; McCabe, Michael T; Pietrak, Beth; Schmidt, Stan; Metallo, Christian M; Dranka, Brian P; Schwartz, Benjamin; DeBerardinis, Ralph J


    Cells receive growth and survival stimuli through their attachment to an extracellular matrix (ECM). Overcoming the addiction to ECM-induced signals is required for anchorage-independent growth, a property of most malignant cells. Detachment from ECM is associated with enhanced production of reactive oxygen species (ROS) owing to altered glucose metabolism. Here we identify an unconventional pathway that supports redox homeostasis and growth during adaptation to anchorage independence. We observed that detachment from monolayer culture and growth as anchorage-independent tumour spheroids was accompanied by changes in both glucose and glutamine metabolism. Specifically, oxidation of both nutrients was suppressed in spheroids, whereas reductive formation of citrate from glutamine was enhanced. Reductive glutamine metabolism was highly dependent on cytosolic isocitrate dehydrogenase-1 (IDH1), because the activity was suppressed in cells homozygous null for IDH1 or treated with an IDH1 inhibitor. This activity occurred in absence of hypoxia, a well-known inducer of reductive metabolism. Rather, IDH1 mitigated mitochondrial ROS in spheroids, and suppressing IDH1 reduced spheroid growth through a mechanism requiring mitochondrial ROS. Isotope tracing revealed that in spheroids, isocitrate/citrate produced reductively in the cytosol could enter the mitochondria and participate in oxidative metabolism, including oxidation by IDH2. This generates NADPH in the mitochondria, enabling cells to mitigate mitochondrial ROS and maximize growth. Neither IDH1 nor IDH2 was necessary for monolayer growth, but deleting either one enhanced mitochondrial ROS and reduced spheroid size, as did deletion of the mitochondrial citrate transporter protein. Together, the data indicate that adaptation to anchorage independence requires a fundamental change in citrate metabolism, initiated by IDH1-dependent reductive carboxylation and culminating in suppression of mitochondrial ROS.

  2. Retention of prolyl hydroxylase PHD2 in the cytoplasm prevents PHD2-induced anchorage-independent carcinoma cell growth

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    Jokilehto, Terhi [Turku Centre for Biotechnology, University of Turku and Abo Akademi University, Turku (Finland); Turku Graduate School of Biomedical Sciences, Turku (Finland); Hoegel, Heidi [Turku Centre for Biotechnology, University of Turku and Abo Akademi University, Turku (Finland); Heikkinen, Pekka [Turku Centre for Biotechnology, University of Turku and Abo Akademi University, Turku (Finland); Turku Graduate School of Biomedical Sciences, Turku (Finland); Rantanen, Krista [Turku Centre for Biotechnology, University of Turku and Abo Akademi University, Turku (Finland); Elenius, Klaus [Department of Oncology and Radiotherapy, University of Turku and Turku University Hospital, Turku (Finland); Department of Medical Biochemistry and Genetics, University of Turku and Turku University Hospital, Turku (Finland); Sundstroem, Jari [Department of Pathology, University of Turku and Turku University Hospital, Turku (Finland); Jaakkola, Panu M. [Turku Centre for Biotechnology, University of Turku and Abo Akademi University, Turku (Finland); Department of Oncology and Radiotherapy, University of Turku and Turku University Hospital, Turku (Finland)


    Cellular oxygen tension is sensed by a family of prolyl hydroxylases (PHD1-3) that regulate the degradation of hypoxia-inducible factors (HIF-1{alpha} and -2{alpha}). The PHD2 isoform is considered as the main downregulator of HIF in normoxia. Our previous results have shown that nuclear translocation of PHD2 associates with poorly differentiated tumor phenotype implying that nuclear PHD2 expression is advantageous for tumor growth. Here we show that a pool of PHD2 is shuttled between the nucleus and the cytoplasm. In line with this, accumulation of wild type PHD2 in the nucleus was detected in human colon adenocarcinomas and in cultured carcinoma cells. The PHD2 isoforms showing high nuclear expression increased anchorage-independent carcinoma cell growth. However, retention of PHD2 in the cytoplasm inhibited the anchorage-independent cell growth. A region that inhibits the nuclear localization of PHD2 was identified and the deletion of the region promoted anchorage-independent growth of carcinoma cells. Finally, the cytoplasmic PHD2, as compared with the nuclear PHD2, less efficiently downregulated HIF expression. Forced HIF-1{alpha} or -2{alpha} expression decreased and attenuation of HIF expression increased the anchorage-independent cell growth. However, hydroxylase-inactivating mutations in PHD2 had no effect on cell growth. The data imply that nuclear PHD2 localization promotes malignant cancer phenotype.

  3. PAX2 regulates ADAM10 expression and mediates anchorage-independent cell growth of melanoma cells.

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    Sophia Boyoung Lee

    Full Text Available PAX transcription factors play an important role during development and carcinogenesis. In this study, we investigated PAX2 protein levels in melanocytes and melanoma cells by Western Blot and immunofluorescence analysis and characterized the role of PAX2 in the pathogenesis of melanoma. In vitro we found weak PAX2 protein expression in keratinocytes and melanocytes. Compared to melanocytes increased PAX2 protein levels were detectable in melanoma cell lines. Interestingly, in tissue sections of melanoma patients nuclear PAX2 expression strongly correlated with nuclear atypia and the degree of prominent nucleoli, indicating an association of PAX2 with a more atypical cellular phenotype. In addition, with chromatin immunoprecipitation assay, PAX2 overexpression and PAX2 siRNA we present compelling evidence that PAX2 can regulate ADAM10 expression, a metalloproteinase known to play important roles in melanoma metastasis. In human tissue samples we found co-expression of PAX2 and ADAM10 in melanocytes of benign nevi and in melanoma cells of patients with malignant melanoma. Importantly, the downregulation of PAX2 by specific siRNA inhibited the anchorage independent cell growth and decreased the migratory and invasive capacity of melanoma cells. Furthermore, the downregulation of PAX2 abrogated the chemoresistance of melanoma cells against cisplatin, indicating that PAX2 expression mediates cell survival and plays important roles during melanoma progression.

  4. Overexpressed EDIL3 predicts poor prognosis and promotes anchorage-independent tumor growth in human pancreatic cancer (United States)

    Feng, Ming-Xuan; Wang, Ya-Hui; Yang, Xiao-Mei; He, Ping; Tian, Guang-Ang; Zhang, Xiao-Xin; Li, Qing; Cao, Xiao-Yan; Huo, Yan-Miao; Yang, Min-Wei; Fu, Xue-Liang; Li, Jiao; Liu, De-Jun; Dai, Miao; Wen, Shan-Yun; Gu, Jian-Ren; Hong, Jie; Hua, Rong; Zhang, Zhi-Gang; Sun, Yong-Wei


    Epidermal Growth Factor-like repeats and Discoidin I-Like Domains 3 (EDIL3), an extracellular matrix (ECM) protein associated with vascular morphogenesis and remodeling, is commonly upregulated in multiple types of human cancers and correlates with tumor progression. However, its expression pattern and underlying cellular functions in pancreatic ductal adenocarcinoma (PDAC) remain largely unexplored. In current study, we observed that expression of EDIL3 was significantly up-regulated in PDAC compared with normal controls in both cell lines and clinical specimens. In addition, elevated EDIL3 expression was positively correlated with patients’ TNM stage and T classification. Kaplan-Meier analysis indicated that high EDIL3 expression was significantly associated with shorter overall survival times in PDAC patients. Multivariate Cox regression analysis confirmed EDIL3 expression, age, lymph node metastasis and histological differentiation as independent prognostic factors in PDAC. Knockdown of EDIL3 showed no significant influence on cell viability, migration, invasion and starvation-induced apoptosis, but compromised anoikis resistance and anchorage independent tumor growth of PDAC cells. Meanwhile, treatment with recombinant EDIL3 protein markedly promoted anoikis resistance and anchorage independent tumor growth. Mechanistically, we demonstrated that altered protein expression of Bcl-2 family might contribute to the oncogenic activities of EDIL3. In conclusion, this study provides evidences that EDIL3 is a potential predictor and plays an important role in anchorage independent tumor growth of PDAC and EDIL3-related pathways might represent a novel therapeutic strategy for treatment of pancreatic cancer. PMID:26735172

  5. ROCK1 and ROCK2 are required for non-small cell lung cancer anchorage-independent growth and invasion. (United States)

    Vigil, Dominico; Kim, Tai Young; Plachco, Ana; Garton, Andrew J; Castaldo, Linda; Pachter, Jonathan A; Dong, Hanqing; Chen, Xin; Tokar, Brianna; Campbell, Sharon L; Der, Channing J


    Evidence is emerging that the closely related ROCK1 and ROCK2 serine/threonine kinases support the invasive and metastatic growth of a spectrum of human cancer types. Therefore, inhibitors of ROCK are under preclinical development. However, a key step in their development involves the identification of genetic biomarkers that will predict ROCK inhibitor antitumor activity. One identified mechanism for ROCK activation in cancer involves the loss of function of the DLC1 tumor suppressor gene, which encodes a GTPase activating protein (RhoGAP) for the RhoA and RhoC small GTPases. DLC-1 loss may lead to hyperactivation of RhoA/C and its downstream effectors, the ROCK kinases. We therefore determined whether loss of DLC-1 protein expression identifies non-small cell lung carcinoma (NSCLC) cell lines whose growth and invasion phenotypes are sensitive to ROCK inhibition. We identified and characterized a novel small molecule pharmacologic inhibitor of ROCK and additionally applied genetic approaches to impair ROCK1 and/or ROCK2 activity, and we determined that although NSCLC anchorage-dependent growth was ROCK-independent, both anchorage-independent growth and Matrigel invasion were ROCK-dependent. However, loss of DLC-1 expression did not correlate with ROCK activation or with OXA-06 sensitivity. Unexpectedly, suppression of ROCK1 or ROCK2 expression alone was sufficient to impair anchorage-independent growth, supporting their nonoverlapping roles in oncogenesis. Mechanistically, the block in anchorage-independent growth was associated with accumulation of cells in the G(0)-G(1) phase of the cell cycle, but not increased anoikis. We conclude that ROCK may be a useful therapeutic target for NSCLC.

  6. Downregulation of Akt1 Inhibits Anchorage-Independent Cell Growth and Induces Apoptosis in Cancer Cells

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    Xuesong Liu


    Full Text Available The serine/threonine kinases, Akti/PKBα, Akt2/PKBβ, and Akt3/PKBγ, play a critical role in preventing cancer cells from undergoing apoptosis. However, the function of individual Akt isoforms in the tumorigenicity of cancer cells is still not well defined. In the current study, we used an AM antisense oligonucleotide (AS to specifically downregulate Akti protein in both cancer and normal cells. Our data indicate that AM AS treatment inhibits the ability of MiaPaCa-2, H460, HCT-15, and HT1080 cells to grow in soft agar. The treatment also induces apoptosis in these cancer cells as demonstrated by FRCS analysis and a caspase activity assay. Conversely, Akti AS treatment has little effect on the cell growth and survival of normal human cells including normal human fibroblast (NHF, fibroblast from muscle (FBM, and mammary gland epithelial 184135 cells. In addition, AM AS specifically sensitizes cancer cells to typical chemotherapeutic agents. Thus, Akti is indispensable for maintaining the tumorigenicity of cancer cells. Inhibition of AM may provide a powerful sensitization agent for chemotherapy specifically in cancer cells.

  7. Leucine zipper structure of TSC-22 (TGF-beta stimulated clone-22) markedly inhibits the anchorage-independent growth of salivary gland cancer cells. (United States)

    Hino, Satoshi; Kawamata, Hitoshi; Omotehara, Fumie; Uchida, Daisuke; Begum, Nasima-Mila; Yoshida, Hideo; Sato, Mitsunobu; Fujimori, Takahiro


    Several investigators have demonstrated that TGF-beta stimulated clone-22 (TSC-22) regulates cell growth and differentiation, and cell death. TSC-22 is a putative transcriptional regulator containing a leucine zipper-like structure and a nuclear export signal. We previously showed the cytoplasmic localization of TSC-22 and the nuclear translocation of TSC-22 concomitant with induction of apoptosis in salivary gland cancer cells. In the present study, we attempted to identify the active domain of TSC-22 protein that regulated the biological functions of TSC-22. We constructed three mammalian expression vectors, which could produce full length TSC-22 only in cytoplasm, the leucine zipper structure of TSC-22 in both cytoplasm and nucleus, and the leucine zipper structure only in nucleus. Then, we transfected a salivary gland cancer cell line, HSG with these expression vectors, and investigated the growth profile of the transfectants. None of the TSC-22 constructs inhibited the monolayer growth and the anchorage-dependent colony formation of HSG cells. However, the leucine zipper structure of TSC-22 markedly inhibited the anchorage-independent colony formation of HSG cells (pway ANOVA). Full length TSC-22 also suppressed the anchorage-independent colony formation of HSG cells, although the effect of full length TSC-22 was much lower than those of the leucine zipper constructs. These observations suggest that the leucine zipper structure in TSC-22 protein is an active domain that negatively regulates the growth of salivary gland cancer cells.

  8. PTK6 regulates IGF-1-induced anchorage-independent survival.

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    Hanna Y Irie

    Full Text Available BACKGROUND: Proteins that are required for anchorage-independent survival of tumor cells represent attractive targets for therapeutic intervention since this property is believed to be critical for survival of tumor cells displaced from their natural niches. Anchorage-independent survival is induced by growth factor receptor hyperactivation in many cell types. We aimed to identify molecules that critically regulate IGF-1-induced anchorage-independent survival. METHODS AND RESULTS: We conducted a high-throughput siRNA screen and identified PTK6 as a critical component of IGF-1 receptor (IGF-1R-induced anchorage-independent survival of mammary epithelial cells. PTK6 downregulation induces apoptosis of breast and ovarian cancer cells deprived of matrix attachment, whereas its overexpression enhances survival. Reverse-phase protein arrays and subsequent analyses revealed that PTK6 forms a complex with IGF-1R and the adaptor protein IRS-1, and modulates anchorage-independent survival by regulating IGF-1R expression and phosphorylation. PTK6 is highly expressed not only in the previously reported Her2(+ breast cancer subtype, but also in high grade ER(+, Luminal B tumors and high expression is associated with adverse outcomes. CONCLUSIONS: These findings highlight PTK6 as a critical regulator of anchorage-independent survival of breast and ovarian tumor cells via modulation of IGF-1 receptor signaling, thus supporting PTK6 as a potential therapeutic target for multiple tumor types. The combined genomic and proteomic approaches in this report provide an effective strategy for identifying oncogenes and their mechanism of action.

  9. Di-Ethylhexylphthalate (DEHP Modulates Cell Invasion, Migration and Anchorage Independent Growth through Targeting S100P in LN-229 Glioblastoma Cells

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    Jennifer Nicole Sims


    Full Text Available Glioblastoma multiforme (GBM is the most aggressive brain cancer with a median survival of 1–2 years. The treatment of GBM includes surgical resection, radiation and chemotherapy, which minimally extends survival. This poor prognosis necessitates the identification of novel molecular targets associated with glioblastoma. S100P is associated with drug resistance, metastasis, and poor clinical outcomes in many malignancies. The functional role of S100P in glioblastoma has not been fully investigated. In this study, we examined the role of S100P mediating the effects of the environmental contaminant, DEHP, in glioblastoma cells (LN-229 by assessing cell proliferation, apoptosis, anchorage independent growth, cell migration and invasion following DEHP exposure. Silencing S100P and DEHP treatment inhibited LN-229 glioblastoma cell proliferation and induced apoptosis. Anchorage independent growth study revealed significantly decreased colony formation in shS100P cells. We also observed reduced cell migration in cells treated with DEHP following S100P knockdown. Similar results were observed in spheroid formation and expansion. This study is the first to demonstrate the effects of DEHP on glioblastoma cells, and implicates S100P as a potential therapeutic target that may be useful as a drug response biomarker.

  10. Induction of anchorage-independent growth in primary human cells exposed to protons or HZE ions separately or in dual exposures. (United States)

    Sutherland, B M; Cuomo, N C; Bennett, P V


    Travelers on space missions will be exposed to a complex radiation environment that includes protons and heavy charged particles. Since protons are present at much higher levels than are heavy ions, the most likely scenario for cellular radiation exposure will be proton exposure followed by a hit by a heavy ion. Although the effects of individual ion species on human cells are being investigated extensively, little is known about the effects of exposure to both radiation types. One useful measure of mammalian cell damage is induction of the ability to grow in a semi-solid agar medium highly inhibitory to the growth of normal human cells, termed neoplastic transformation. Using primary human cells, we evaluated induction of soft-agar growth and survival of cells exposed to protons only or to heavy charged particles (600 MeV/nucleon silicon) only as well as of cells exposed to protons followed after a 4-day interval by silicon ions. Both ions alone efficiently transformed the human cells to anchorage-independent growth. Initial experiments indicate that the dose responses for neoplastic transformation of cells exposed to protons and then after 4 days to silicon ions appear similar to that of cells exposed to silicon ions alone.

  11. Upregulation of DNA methyltransferase-mediated gene silencing, anchorage-independent growth, and migration of colon cancer cells by interleukin-6. (United States)

    Foran, Eilis; Garrity-Park, Megan M; Mureau, Coralie; Newell, John; Smyrk, Thomas C; Limburg, Paul J; Egan, Laurence J


    Inflammatory bowel disease is characterized by chronic inflammation which predisposes to colorectal cancer. The mechanisms by which inflammation promotes tumorigenesis are not fully known. We aimed to investigate the links between colonic inflammation and tumorigenesis via epigenetic gene silencing. Colon cancer specimens were assessed for the expression of DNA methyltransferase-1 (DNMT-1) using immunohistochemistry. Colorectal carcinoma cell lines were assessed for DNMT1 expression, methylcytosine content, promoter methylation, gene expression, and tumorigenesis in response to interleukin (IL)-6. DNMT1 was expressed at higher levels in both the peritumoral stroma and tumor in inflammatory bowel disease-associated cancers compared with sporadic colon cancers. IL-6 treatment of colon cancer cells resulted in an increase in DNMT1 expression, independent of de novo gene expression. IL-6 increased the methylation of promoter regions of genes associated with tumor suppression, adhesion, and apoptosis resistance. Expression of a subset of these genes was downregulated by IL-6, an effect that was prevented by preincubation with 5-azadeoxycytidine, a DNMT1 inhibitor. Anchorage-independent growth and migration of colon cancer cells was also increased by IL-6 in a 5-azadeoxycytidine-sensitive manner. Our results indicate that DNMT-mediated gene silencing may play a role in inflammation-associated colon tumorigenesis.

  12. Cellular Dichotomy Between Anchorage-Independent Growth Responses to bFGF and TA Reflects Molecular Switch in Commitment to Carcinogenesis

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    Waters, Katrina M.; Tan, Ruimin; Opresko, Lee K.; Quesenberry, Ryan D.; Bandyopadhyay, Somnath; Chrisler, William B.; Weber, Thomas J.


    We have investigated gene expression patterns underlying reversible and irreversible anchorage-independent growth (AIG) phenotypes to identify more sensitive markers of cell transformation for studies directed at interrogating carcinogenesis responses. In JB6 mouse epidermal cells, basic fibroblast growth factor (bFGF) induces an unusually efficient and reversible AIG response, relative to 12-O-tetradecanoyl phorbol-13-acetate (TPA)-induced AIG which is irreversible. The reversible and irreversible AIG phenotypes are characterized by largely non-overlapping global gene expression profiles. However, a subset of differentially expressed genes were identified as common to reversible and irreversible AIG phenotypes, including genes regulated in a reciprocal fashion. Hepatic leukemia factor (HLF) and D-site albumin promoter-binding protein (DBP) were increased in both bFGF and TPA soft agar colonies and selected for functional validation. Ectopic expression of human HLF and DBP in JB6 cells resulted in a marked increase in TPA- and bFGF-regulated AIG responses. HLF and DBP expression were increased in soft agar colonies arising from JB6 cells exposed to gamma radiation and in a human basal cell carcinoma tumor tissue, relative to paired non-tumor tissue. Subsequent biological network analysis suggests that many of the differentially expressed genes that are common to bFGF- and TPA-dependent AIG are regulated by c-Myc, SP-1 and HNF-4 transcription factors. Collectively, we have identified a potential molecular switch that mediates the transition from reversible to irreversible AIG.

  13. MicroRNA let-7b targets important cell cycle molecules in malignant melanoma cells and interferes with anchorage-independent growth

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    Julia Schultz; Peter Lorenz; Gerd Gross; Saleh Ibrahim; Manfred Kunz


    A microRNA expression screen was performed analyzing 157 different microRNAs in laser-microdissected tissues from benign melanocytic nevi (n=10) and primary malignant melanomas (n=10),using quantitative real-time PCR.Differential expression was found for 72 microRNAs.Members of the let-7 family of microRNAs were significantly downregulated in primary melanomas as compared with benign nevi,suggestive for a possible role of these molecules as tumor suppressors in malignant melanoma.Interestingly,similar findings had been described for lung and colon cancer.Overexpression of let-7b in melanoma cells in vitro downregulated the expression of cyclins D1,D3,and A,and cyclin-dependent kinase (Cdk) 4,all of which had been described to play a role in melanoma development.The effect oflet-7b on protein expression was due to targeting of 3'-untranslated regions (3'UTRs) of individual mRNAs,as exemplified by reporter gene analyses for cyclin DI.In line with its downmodulating effects on cell cycle regulators,let-7b inhibited cell cycle progression and anchorage-independent growth of melanoma cells.Taken together,these findings not only point to new regulatory mechanisms of early melanoma development,but also may open avenues for future targeted therapies of this tumor.

  14. ROCK1 and ROCK2 are Required for Non-Small Cell Lung Cancer Anchorage-Independent Growth and Invasion


    Vigil, Dominico; Kim, Tai Young; Plachco, Ana; Garton, Andrew J.; Castaldo, Linda; Pachter, Jonathan A.; Dong, Hanqing; Chen, Xin; Tokar, Brianna; Campbell, Sharon L.; Der, Channing J.


    Evidence is emerging that the closely related ROCK1 and ROCK2 serine/threonine kinases support the invasive and metastatic growth of a spectrum of human cancer types. Therefore, inhibitors of ROCK are under preclinical development. However, a key step in their development involves the identification of genetic biomarkers that will predict ROCK inhibitor anti-tumor activity. One identified mechanism for ROCK activation in cancer involves the loss of function of the DLC1 tumor suppressor gene, ...

  15. Anchorage-independent growth of pocket protein-deficient murine fibroblasts requires bypass of G2 arrest and can be accomplished by expression of TBX2

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    Vormer, Tinke L; Foijer, Floris; Wielders, Camiel L C; te Riele, Hein


    Mouse embryonic fibroblasts (MEFs) deficient for pocket proteins (i.e., pRB/p107-, pRB/p130-, or pRB/p107/p130-deficient MEFs) have lost proper G(1) control and are refractory to Ras(V12)-induced senescence. However, pocket protein-deficient MEFs expressing Ras(V12) were unable to exhibit anchorage-

  16. Missense mutations in pyruvate kinase M2 promote cancer metabolism, oxidative endurance, anchorage independence, and tumor growth in a dominant negative manner. (United States)

    Iqbal, Mohd Askandar; Siddiqui, Farid Ahmad; Chaman, Noor; Gupta, Vibhor; Kumar, Bhupender; Gopinath, Prakasam; Bamezai, Rameshwar N K


    The present study was designed to examine the functional relevance of two heterozygous mutations (H391Y and K422R), observed earlier by us in the Bloom syndrome condition. Cells stably expressing exogenous wild-type or mutant PKM2 (K422R or H391Y) or co-expressing both wild type and mutant (PKM2-K422R or PKM2-H391Y) were assessed for cancer metabolism and tumorigenic potential. Interestingly, cells co-expressing PKM2 and mutant (K422R or H391Y) showed significantly aggressive cancer metabolism as compared with cells expressing either wild-type or mutant PKM2 independently. A similar trend was observed for oxidative endurance, tumorigenic potential, cellular proliferation, and tumor growth. These observations signify the dominant negative nature of mutations. Remarkably, PKM2-H391Y co-expressed cells showed a maximal effect on all the studied parameters. Such a dominant negative impaired function of PKM2 in tumor development is not known; this study demonstrates for the first time the possible predisposition of Bloom syndrome patients with impaired PKM2 activity to cancer and the importance of studying genetic variations in PKM2 in the future to understand their relevance in cancer in general.

  17. Concrete Growth and Fatigue Analysis of Chickamauga Lock Miter Gate Anchorages (United States)


    a review of existing structural analysis reports, estimates and prediction of observed concrete growth in the area near the anchorages, and estimates. The fatigue life estimates included the concrete growth estimates and also included the stresses and strains taken from measurements...existing anchorages and considerations for if and when the anchorages are replaced.

  18. CD45/CD11b Positive Subsets of Adult Lung Anchorage-Independent Cells Harness Epithelial Stem Cells



    Compensatory growth is mediated by multiple cell types that interact during organ repair. To elucidate the relationship between the stem/progenitor cells that proliferate or differentiate and the somatic cells of lung, we utilized a novel ex vivo pneumoexplant system. Applying this technique, we identified a sustained culture of repopulating adult progenitors in the form of free floating anchorage-independent cells (AICs). AICs did not express integrin proteins α5, β3, and β7, and constituted...

  19. CD45/CD11b Positive Subsets of Adult Lung Anchorage-Independent Cells Harness Epithelial Stem Cells (United States)

    Peter, Yakov; Sen, Namita; Levantini, Elena; Keller, Steven; Ingenito, Edward P; Ciner, Aaron; Sackstein, Robert; Shapiro, Steven D


    Compensatory growth is mediated by multiple cell types that interact during organ repair. To elucidate the relationship between the stem/progenitor cells that proliferate or differentiate and the somatic cells of lung, we utilized a novel ex vivo pneumoexplant system. Applying this technique, we identified a sustained culture of repopulating adult progenitors in the form of free floating anchorage-independent cells (AICs). AICs did not express integrin proteins α5, β3, and β7, and constituted 37% of the total culture at day 14, yielding a mixed yet conserved population that recapitulated RNA expression patterns of the healthy lung. AICs exhibited rapid proliferation manifested by a marked 60-fold increase in cell numbers by day 21. Over 50% of the AIC population was cKit+ or double-positive for CD45+ and CD11b+ antigenic determinants, consistent with cells of hematopoietic origin. The latter subset was found to be enriched with prosurfactant protein-C and SCGB1A1 expressing putative stem cells and with aquaporin-5 producing cells, characteristic of terminally differentiated alveolar epithelial type-1 pneumocytes. AICs undergo remodeling to form a cellular lining at the air/gel interface, and TGFβ1 treatment modifies protein expression, implying direct-differentiation of this population. These data confirm the active participation of clonogenic hematopietic stem cells in a mammalian model of lung repair and validate mixed stem/somatic cell cultures, which embrace sustained cell viability, proliferation, and differentiation, for use in studies of compensatory pulmonary growth. PMID:22585451

  20. Segregated mathematical model for growth of anchorage-dependent MDCK cells in microcarrier culture. (United States)

    Möhler, Lars; Bock, Andreas; Reichl, Udo


    To describe the growth behavior of anchorage-dependent mammalian cells in microcarrier systems, various approaches comprising deterministic and stochastic single cell models as well as automaton-based models have been presented in the past. The growth restriction of these often contact-inhibited cells by spatial effects is described at levels with different complexity but for the most part not taking into account their metabolic background. Compared to suspension cell lines these cells have a comparatively long lag phase required for attachment and start of proliferation on the microcarrier. After an initial phase of exponential growth only a moderate specific growth rate is achieved due to restrictions in space available for cell growth, limiting medium components, and accumulation of growth inhibitors. Here, a basic deterministic unstructured segregated cell model for growth of Madin Darby Canine Kidney (MDCK) cells used in influenza vaccine production is described. Four classes of cells are considered: cells on microcarriers, cells in suspension, dead cells, and lysed cells. Based on experimental data, cell attachment and detachment is taken explicitly into account. The model allows simulation of the overall growth behavior in microcarrier culture, including the lag phase. In addition, it describes the time course of uptake and release of key metabolites and the identification of parameters relevant for the design and optimization of vaccine manufacturing processes.

  1. Anchorage of mature conifers: resistive turning moment, root-soil plate geometry and root growth orientation. (United States)

    Lundström, Tor; Jonas, Tobias; Stöckli, Veronika; Ammann, Walter


    Eighty-four mature Norway spruce (Picea abies L. Karst), silver fir (Abies alba Mill) and Scots pine (Pinus sylvestris L.) trees were winched over to determine the maximum resistive turning moment (M(a)) of the root-soil system, the root-soil plate geometry, the azimuthal orientation of root growth, and the occurrence of root rot. The calculation of M(a), based on digital image tracking of stem deflection, accounted not only for the force application and its changing geometry, but also for the weight of the overhanging tree, representing up to 42% of M(a). Root rot reduced M(a) significantly and was detected in 25% of the Norway spruce and 5% of the silver fir trees. Excluding trees with root rot, differences in M(a) between species were small and insignificant. About 75% of the variance in M(a) could be explained by one of the four variables--tree mass, stem mass, stem diameter at breast height squared times tree height, and stem diameter at breast height squared. Among the seven allometric variables assessed above ground, stem diameter at breast height best described the root-soil plate dimensions, but the correlations were weak and the differences between species were insignificant. The shape of the root-soil plate was well described by a depth-dependent taper model with an elliptical cross section. Roots displayed a preferred azimuthal orientation of growth in the axis of prevailing winds, and the direction of frequent weak winds matched the orientation of growth better than that of rare strong winds. The lack of difference in anchorage parameters among species probably reflects the similar belowground growth conditions of the mature trees.

  2. Chlamydia induces anchorage independence in 3T3 cells and detrimental cytological defects in an infection model.

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    Andrea E Knowlton

    Full Text Available Chlamydia are gram negative, obligate intracellular bacterial organisms with different species causing a multitude of infections in both humans and animals. Chlamydia trachomatis is the causative agent of the sexually transmitted infection (STI Chlamydia, the most commonly acquired bacterial STI in the United States. Chlamydial infections have also been epidemiologically linked to cervical cancer in women co-infected with the human papillomavirus (HPV. We have previously shown chlamydial infection results in centrosome amplification and multipolar spindle formation leading to chromosomal instability. Many studies indicate that centrosome abnormalities, spindle defects, and chromosome segregation errors can lead to cell transformation. We hypothesize that the presence of these defects within infected dividing cells identifies a possible mechanism for Chlamydia as a cofactor in cervical cancer formation. Here we demonstrate that infection with Chlamydia trachomatis is able to transform 3T3 cells in soft agar resulting in anchorage independence and increased colony formation. Additionally, we show for the first time Chlamydia infects actively replicating cells in vivo. Infection of mice with Chlamydia results in significantly increased cell proliferation within the cervix, and in evidence of cervical dysplasia. Confocal examination of these infected tissues also revealed elements of chlamydial induced chromosome instability. These results contribute to a growing body of data implicating a role for Chlamydia in cervical cancer development and suggest a possible molecular mechanism for this effect.

  3. fau and its ubiquitin-like domain (FUBI) transforms human osteogenic sarcoma (HOS) cells to anchorage-independence. (United States)

    Rossman, Toby G; Visalli, Melissa A; Komissarova, Elena V


    Arsenite is the most likely carcinogenic form of arsenic in the environment. Previously, expression cloning for cDNAs whose overexpression confers arsenite-resistance in Chinese hamster V79 cells identified two genes: fau and a novel gene, asr2. The fau gene encodes a ubiquitin-like protein (here called FUBI) fused to the ribosomal S30 protein. Since the expression of the fox sequence (antisense to fau) increased the tumorigenicity of a mouse sarcoma virus, it was proposed that fau might be a tumor suppressor gene. We intended to test its ability to block arsenite-induced transformation of human osteogenic sarcoma (HOS) cells to anchorage-independence. Instead, we found that overexpressing fau itself was able to transform HOS cells. When the two domains were expressed separately, only FUBI was transforming and only the S30 domain conferred arsenite resistance. An incidental finding was the transforming activity of the selectable marker, hyg. FUBI belongs to the ubiquitin-like protein group that is capable of forming conjugates to other proteins, although none have so far been identified. Alternatively, FUBI may act as a substitute or inhibitor of ubiquitin, to which it is most closely related, or to close ubiquitin-like relatives UCRP, FAT10, and/or Nedd8.

  4. Doxycycline-Regulated p16(MTS1) Expression Suppresses the Anchorage-Independence and Tumorigenicity of Breast Cancer Cell Lines that Lack Endogenous p16. (United States)

    Todd, Maria C; Langan, Thomas A; Sclafani, Robert A


    The RB pathway controls the critical transition from G1 into S phase of the mammalian cell cycle. Deregulation of the RB pathway by means of RB or p16 inactivation has been implicated in the development of virtually all human cancers. Such findings have led to the view that the loss of RB-mediated regulation at the G1/S checkpoint is a precondition for human malignancy. Our analysis of the RB-positive MCF-7 and ZR75.1 breast cancer cell lines revealed a lack of endogenous p16 protein expression as a result of the homozygous deletion and methylation of the p16 gene at the CDKN2A locus, respectively. We employed the TET-OFF inducible expression system to investigate the effects of non-growth inhibitory levels of functional p16 protein upon the in vitro and in vivo transformed properties of the MCF-7 and ZR75.1 cell lines. Stable transfectants of MCF-7 and ZR75.1 cells were isolated that expressed different levels of p16 protein in the absence of doxycycline (DOX) but continued to proliferate in culture. Transfectants that expressed modest levels of p16 (relative to SV40 T antigen-transformed HBL-100 breast epithelial cells) demonstrated a marked suppression of anchorage-independent growth in soft agar. Further, the induction of moderate and high levels of p16 (relative to HBL-100) resulted in the suppression of tumorigenicity of both MCF-7 and ZR75.1 cells as assayed by injection into nude mice. From these data, we concluded that RB pathway restoration by non-growth inhibitory levels of p16 protein was sufficient to revert breast cancer cells to a non-transformed and non-tumorigenic state.

  5. Doxycycline-Regulated p16MTS1 Expression Suppresses the Anchorage-Independence and Tumorigenicity of Breast Cancer Cell Lines that Lack Endogenous p16 (United States)

    Todd, Maria C; Langan, Thomas A; Sclafani, Robert A


    The RB pathway controls the critical transition from G1 into S phase of the mammalian cell cycle. Deregulation of the RB pathway by means of RB or p16 inactivation has been implicated in the development of virtually all human cancers. Such findings have led to the view that the loss of RB-mediated regulation at the G1/S checkpoint is a precondition for human malignancy. Our analysis of the RB-positive MCF-7 and ZR75.1 breast cancer cell lines revealed a lack of endogenous p16 protein expression as a result of the homozygous deletion and methylation of the p16 gene at the CDKN2A locus, respectively. We employed the TET-OFF inducible expression system to investigate the effects of non-growth inhibitory levels of functional p16 protein upon the in vitro and in vivo transformed properties of the MCF-7 and ZR75.1 cell lines. Stable transfectants of MCF-7 and ZR75.1 cells were isolated that expressed different levels of p16 protein in the absence of doxycycline (DOX) but continued to proliferate in culture. Transfectants that expressed modest levels of p16 (relative to SV40 T antigen-transformed HBL-100 breast epithelial cells) demonstrated a marked suppression of anchorage-independent growth in soft agar. Further, the induction of moderate and high levels of p16 (relative to HBL-100) resulted in the suppression of tumorigenicity of both MCF-7 and ZR75.1 cells as assayed by injection into nude mice. From these data, we concluded that RB pathway restoration by non-growth inhibitory levels of p16 protein was sufficient to revert breast cancer cells to a non-transformed and non-tumorigenic state.

  6. Anchorage Areas (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — An anchorage area is a place where boats and ships can safely drop anchor. These areas are created in navigable waterways when ships and vessels require them for...

  7. New concept of physiologic anchorage control

    Directory of Open Access Journals (Sweden)

    Tian-Min Xu


    Full Text Available Molar anchorage loss in extraction case is believed due to the reaction of mechanical force applied to retract anterior teeth. While it may be close to truth in adult patients, it is certainly not true in adolescents. Studies on molar growth show upper molar move forward as mandible growing forward, probably through intercuspation force. Hence, for adolescents, molar anchorage loss shall consist of two parts. One is from retraction force - mechanical anchorage loss; another from biologic force - physiologic anchorage loss. Since physiologic anchorage loss is caused by the continuous biologic force, the strategy of physiologic anchorage control (PAC is different from the strategy of mechanical anchorage control. A new PAC method is introduced in this article that can reduce the headgear and temporary anchorage device used as sagittal anchorage dramatically in orthodontic clinic.

  8. Classically activated macrophages promote anchorage-dependent and anchorage-independent clone formation of breast cancer cells%经典激活巨噬细胞促进乳腺癌细胞贴壁和非贴壁克隆形成

    Institute of Scientific and Technical Information of China (English)

    陈静琦; 朱必胜; 侯开连


    目的 探讨经典激活巨噬细胞(M1)对乳腺癌细胞贴壁和非贴壁克隆形成的影响,进一步阐明M1促乳腺癌进展的作用.方法 用密度梯度离心法,从健康成人外周血中分离单个核细胞,体外诱导M1.在乳腺癌细胞与巨噬细胞的无血清共培养体系中,做平板克隆实验;在M1-乳腺癌细胞软琼脂培养体系中,做非贴壁克隆形成实验,检测M1对乳腺癌贴壁克隆和非贴壁克隆形成的影响.结果 在M1的作用下,乳腺癌SK-3rd细胞贴壁克隆和非贴壁克隆形成的能力均增强(P<0.001).结论 M1促进乳腺癌细胞贴壁克隆和非贴壁克隆的形成.%Objective To investigate the effect of activated microphages (M1) on the clone formation of breast cancer cells.Methods Mononuclear cells were isolated from peripheral blood of adult normal subjects by density gradient centrifugation,and M1 was induced in vitro.In the serum-free co-culture system of breast cancer cells and macrophages,the fiat cloning assay was performed and in soft agar culture system of Ml-breast cancer cells,anchorage-independent clone formation assay was performed.Results The anchorage-dependent and anchorage-independent clone formation of SK-3rd breast cancer cells was induced by M1 (P < 0.001).Conclusion M1 promotes anchorage-dependent and anchorage-independent clone formation of breast cancer cells.

  9. TERRAIN, Anchorage, Alaska (United States)

    Federal Emergency Management Agency, Department of Homeland Security — The Anchorage AOI consists of seven areas. These areas were to be collected to the 'highest' accuracy requirement. Ground Control is collected throughout the AOI for...

  10. Onplant-supported orthodontic anchorage. (United States)

    Armbruster, P C; Block, M S


    The use of onplant-supported orthodontic anchorage is still in its early stages. The concepts presented in this article have tried to stress the importance of anchorage control in orthodontic cases, some problems associated with traditional means to augment orthodontic anchorage, the rationale for developing a skeletal anchorage unit based on endosseous implant technology, and the effectiveness of the onplant as an anchorage unit. Cephalometric superimpositions are most likely the best method to determine the effectiveness of the onplant's contribution to anchorage control and have been included here to that end. Further research into its effectiveness may broaden the use of onplants in future orthodontic cases.

  11. Down-regulation of Survivin by Antisense Oligonucleotides Increases Apoptosis, Inhibits Cytokinesis and Anchorage-Independent Growth

    Directory of Open Access Journals (Sweden)

    Jun Chen


    Full Text Available Survivin, a member of the inhibitor of apoptosis protein (IAP family, is detected in most common human cancers but not in adjacent normal cells. Previous studies suggest that survivin associates with the mitotic spindle and directly inhibits caspase activity. To further investigate the function of survivin, we used a survivin antisense (AS oligonucleotide to downregulate survivin expression in normal and cancer cells. We found that inhibition of survivin expression increased apoptosis and polyploidy while decreasing colony formation in soft agar. Immunohistochemistry showed that cells without survivin can initiate the cleavage furrow and contractile ring, but cannot complete cytokinesis, thus resulting in multinucleated cells. These findings indicate that survivin plays important roles in a late stage of cytokinesis, as well as in apoptosis.

  12. The LKB1 tumor suppressor differentially affects anchorage independent growth of HPV positive cervical cancer cell lines

    Energy Technology Data Exchange (ETDEWEB)

    Mack, Hildegard I.D.; Munger, Karl, E-mail:


    Infection with high-risk human papillomaviruses is causally linked to cervical carcinogenesis. However, most lesions caused by high-risk HPV infections do not progress to cancer. Host cell mutations contribute to malignant progression but the molecular nature of such mutations is unknown. Based on a previous study that reported an association between liver kinase B1 (LKB1) tumor suppressor loss and poor outcome in cervical cancer, we sought to determine the molecular basis for this observation. LKB1-negative cervical and lung cancer cells were reconstituted with wild type or kinase defective LKB1 mutants and we examined the importance of LKB1 catalytic activity in known LKB1-regulated processes including inhibition of cell proliferation and elevated resistance to energy stress. Our studies revealed marked differences in the biological activities of two kinase defective LKB1 mutants in the various cell lines. Thus, our results suggest that LKB1 may be a cell-type specific tumor suppressor. - Highlights: • LKB1 is a tumor suppressor that is linked to Peutz-Jeghers syndrome. • Peutz-Jeghers syndrome patients have a high incidence of cervical cancer. • Cervical cancer is caused by HPV infections. • This study investigates LKB1 tumor suppressor activity in cervical cancer.

  13. KSHV MicroRNAs Repress Tropomyosin 1 and Increase Anchorage-Independent Growth and Endothelial Tube Formation.

    Directory of Open Access Journals (Sweden)

    Philippe Kieffer-Kwon

    Full Text Available Kaposi's sarcoma (KS is characterized by highly vascularized spindle-cell tumors induced after infection of endothelial cells by Kaposi's sarcoma-associated herpesvirus (KSHV. In KS tumors, KSHV expresses only a few latent proteins together with 12 pre-microRNAs. Previous microarray and proteomic studies predicted that multiple splice variants of the tumor suppressor protein tropomyosin 1 (TPM1 were targets of KSHV microRNAs. Here we show that at least two microRNAs of KSHV, miR-K2 and miR-K5, repress protein levels of specific isoforms of TPM1. We identified a functional miR-K5 binding site in the 3' untranslated region (UTR of one TPM1 isoform. Furthermore, the inhibition or loss of miR-K2 or miR-K5 restores expression of TPM1 in KSHV-infected cells. TPM1 protein levels were also repressed in KSHV-infected clinical samples compared to uninfected samples. Functionally, miR-K2 increases viability of unanchored human umbilical vein endothelial cells (HUVEC by inhibiting anoikis (apoptosis after cell detachment, enhances tube formation of HUVECs, and enhances VEGFA expression. Taken together, KSHV miR-K2 and miR-K5 may facilitate KSHV pathogenesis.

  14. Effect of surface active compounds on growth and adhesion of anchorage-dependent animal cells at liquid/liquid interface; Eki/ekikaimen ni okeru fuchaku izonsei dobutsu saibo no zoshoku oyobi fuchaku ni taisuru kaimen kassei busshitsu no eikyo

    Energy Technology Data Exchange (ETDEWEB)

    Shiba, Y.; Oshima, T.; Sato, M. [Gunma Univ., Kiryu (Japan). Faculty of Technology


    A cell cultivation using a liquid/liquid (culture medium/fluorocarbon) interface has been practiced as a novel culturing method for anchorage-dependent animal cells, and it is known that cell adhesion at the interface is dependent on the contaminants contained in the hydrophobic liquid. Substances effective for the adhesion and growth of cells are investigated using various surfactants. As a result of comparison of ionic and nonionic surfactants, cell adhesion is observed when ionic surfactant is used, indicating the importance of the electric charge of surfactant. Cell growth is better when ionic surfactant is added to fluorocarbon than when surfactant is added to the culture medium. The cell growth using fluorocarbon added with pentafluorobenzoyl chloride and perfluorooctanoyl chloride is similar to that of culturing using polystyrene, and the importance of surfactant addition to fluorocarbon is indicated. 7 refs., 4 figs.

  15. Constrained growth of complex scale-independent systems (United States)

    Hébert-Dufresne, Laurent; Allard, Antoine; Young, Jean-Gabriel; Dubé, Louis J.


    Scale independence is a ubiquitous feature of complex systems that implies a highly skewed distribution of resources with no characteristic scale. Research has long focused on why systems as varied as protein networks, evolution, and stock actions all feature scale independence. Assuming that they simply do, we focus here on describing how this behavior emerges, in contrast to more idealized models usually considered. We arrive at the conjecture that a minimal model to explain the growth toward scale independence involves only two coupled dynamical features: the first is the well-known preferential attachment principle, and the second is a general form of delayed temporal scaling. While the first is sufficient, the second is present in all studied data and appears to maximize the speed of convergence to true scale independence. The delay in this temporal scaling acts as a coupling between population growth and individual activity. Together, these two dynamical properties appear to pave a precise evolution path, such that even an instantaneous snapshot of a distribution is enough to reconstruct the past of the system and predict its future. We validate our approach and confirm its usefulness in diverse spheres of human activities, ranging from scientific and artistic productivity to sexual relations and online traffic.

  16. Insulin-Like Growth Factor-Independent Effects of Growth Hormone on Growth Plate Chondrogenesis and Longitudinal Bone Growth. (United States)

    Wu, Shufang; Yang, Wei; De Luca, Francesco


    GH stimulates growth plate chondrogenesis and longitudinal bone growth directly at the growth plate. However, it is not clear yet whether these effects are entirely mediated by the local expression and action of IGF-1 and IGF-2. To determine whether GH has any IGF-independent growth-promoting effects, we generated (TamCart)Igf1r(flox/flox) mice. The systemic injection of tamoxifen in these mice postnatally resulted in the excision of the IGF-1 receptor (Igf1r) gene exclusively in the growth plate. (TamCart)Igf1r(flox/flox) tamoxifen-treated mice [knockout (KO) mice] and their Igf1r(flox/flox) control littermates (C mice) were injected for 4 weeks with GH. At the end of the 4-week period, the tibial growth and growth plate height of GH-treated KO mice were greater than those of untreated C or untreated KO mice. The systemic injection of GH increased the phosphorylation of Janus kinase 2 and signal transducer and activator of transcription 5B in the tibial growth plate of the C and KO mice. In addition, GH increased the mRNA expression of bone morphogenetic protein-2 and the mRNA expression and protein phosphorylation of nuclear factor-κB p65 in both C and KO mice. In cultured chondrocytes transfected with Igf1r small interfering RNA, the addition of GH in the culture medium significantly induced thymidine incorporation and collagen X mRNA expression. In conclusion, our findings demonstrate that GH can promote growth plate chondrogenesis and longitudinal bone growth directly at the growth plate, even when the local effects of IGF-1 and IGF-2 are prevented. Further studies are warranted to elucidate the intracellular molecular mechanisms mediating the IGF-independent, growth-promoting GH effects.

  17. 33 CFR 401.50 - Anchorage areas. (United States)


    ... 33 Navigation and Navigable Waters 3 2010-07-01 2010-07-01 false Anchorage areas. 401.50 Section... TRANSPORTATION SEAWAY REGULATIONS AND RULES Regulations Seaway Navigation § 401.50 Anchorage areas. Except in an... of the Seaway except in the following designated anchorage areas: (a) Point Fortier (Lake St....

  18. [Different orthodontic anchorage systems. A critical examination]. (United States)

    Diedrich, P


    Every orthodontic measure requires a detailed analysis of the individual anchorage situation in order to absorb (stationary anchorage) or control (reciprocal anchorage) the reactive forces and moments. Basically, an anchorage is oriented to the quality of the biological anchorage of the teeth. This is influenced by a number of factors: size of root surface, attachment level, density and structure of alveolar bone, periodontal reactivity, muscular activity, occlusal forces, craniofacial morphology and the nature of the tooth movement resulting from the planned correction. The quality of the biological anchorage may be enhanced by selective modification of the position of the anchor teeth: cortical anchorage of the first molar (Ricketts), distal inclination of the molars (Tweed, Begg) and differential torque control (Burstone). In this context, undesired anchorage effects also need to be discussed, for example interaction between the teeth being corrected and compact bone structures (symphysis menti, floor of the maxillary sinus) or the loss of anchorage by periodontal hyalinization or excessive friction within the bracket slot. In addition, the anchorage situation of ankylosed teeth and endosseous implants, as well as the advantages and disadvantages of additional mechanical anchorage aids (head-gear, Nance holding arch, lingual arch) are discussed. On the basis of the complexity of the individual biological and biomechanical aspects, guidelines are derived with which to establish anchorage control matched to the specific situation.

  19. Independence of sialic acid levels in normal and malignant growth. (United States)

    Khadapkar, S V; Sheth, N A; Bhide, S V


    Sialic acid content in breast or tumor tissue and serum of mouse strains that are either susceptible or resistant to breast cancer was measured at various age periods. Sialic acid content was also studied in normal lung tissue and in lung adenoma and hepatoma. Sialic acid levels during nonmalignant growth of a tissue were measured in breast tissue during pregnancy and lactation, and in regenerating liver, as well as in newborn and postnatal liver. The sialic acid content, when expressed per mg of protein, increased in mammary tumor, lung adenoma, and hepatoma. It also increased in nonmalignant growth of breast tissue during pregnancy and lactation and of regenerating liver and postnatal liver. Increase in sialic acid per mg DNA was observed only in lung tumors, regenerating liver, and postnatal liver. It appears that the changes in sialic acid level are independent of the normal or malignant growth of a tissue and that these changes might be the function of the parameter used to express the sialic acid values, i.e., either the DNA content or protein content of a given tissue.

  20. 77 FR 25587 - Anchorage Regulations; Wells, ME (United States)


    ... SECURITY Coast Guard 33 CFR Part 110 RIN 1625-AA01 Anchorage Regulations; Wells, ME AGENCY: Coast Guard... three special anchorage areas in Wells Harbor, Wells, Maine, through a published final rule. The Marine.... Viewing Comments and Documents To view comments, as well as documents mentioned in this preamble as...

  1. 76 FR 52599 - Anchorage Regulations; Wells, ME (United States)


    ... SECURITY Coast Guard 33 CFR Part 110 RIN 1625-AA01 Anchorage Regulations; Wells, ME AGENCY: Coast Guard... special anchorage areas in Wells Harbor, Wells, Maine. This proposed action is necessary to facilitate... in length. This action is intended to increase the safety of life and property in Wells...

  2. Latin American Growth-Inequality Trade-Offs: The Impact of Insurgence and Independence



    Did independence push Latin America down a growth-inequality trade-off? During the late colonial decades, the region completed two centuries of growth unmatched anywhere and inequality reached spectacular heights. During the half century after insurgency and independence, inequality fell steeply and growth was so modest that the period is called the lost decades. With the appearance of the belle époque in the 1870s, growth rose to impressive levels, again even by world standards, and inequali...

  3. Cytochrome c2-independent respiratory growth of Rhodobacter capsulatus.


    Daldal, F


    To assess the role of cytochrome c2 as a respiratory electron carrier, we obtained a double mutant of Rhodobacter capsulatus defective in cytochrome c2 and in the quinol oxidase260. This mutant was able to grow chemoheterotrophically, indicating that an electron pathway independent of cytochrome c2 was functional between the ubiquinol:cytochrome c2 oxidoreductase and the cytochrome oxidase410.

  4. Orthodontic Anchorage Implants: State-of-the-art

    DEFF Research Database (Denmark)

    Melsen, Birte


    The limits of an orthodontic treatment are often set by the lack of suitable anchorage. The mini-implant is used where conventional anchorage cannot be applied and not as a replacement for conventional anchorage. In patients with lack of teeth and reduced periodontium, skeletal anchorage allows...... will improve the reconstruction possibilities. The mini-implant has widened the orthodontic possibilities....

  5. Hypergravity inhibits elongation growth of azuki bean epicotyls independently of the direction of stimuli (United States)

    Soga, K.; Wakabayashi, K.; Kamisaka, S.; Hoson, T.

    We examined the effects of basipetal, horizontal, and acropetal hypergravity stimulation on growth and cell wall properties of azuki bean seedlings. Horizontal and acropetal hypergravity inhibited elongation growth of epicotyls by decreasing the cell wall extensibility, as did basipetal hypergravity. Hypergravity stimulation increased the thickness of cell walls and suppressed xyloglucan breakdown regardless of direction. All hypergravity treatments increased the pH in the apoplastic fluid, which is involved in the processes of the suppression of xyloglucan breakdown. Gadolinium and lanthanum, both blockers of mechanoreceptors, nullified the growth-inhibiting effects of hypergravity. These results show that growth inhibition by hypergravity is independent of its direction in azuki bean epicotyls. The findings also suggest that mechanoreceptors on the plasma membrane perceive the gravity signal independently of its direction, and affect growth of azuki bean epicotyls.

  6. Is skeletal anchorage changing the limit of orthodontics?

    DEFF Research Database (Denmark)

    Melsen, Birte


    The limits for orthodontic treatment are often set by the lack of suitable anchorage. The mini-implant is used where conventional anchorage cannot be applied; not as a replacement for conventional anchorage. In patients with lack of teeth and reduced periodontium, skeletal anchorage allows...... and can be loaded immediately. The course will be addressed the following topics: Are the mini-implants replacing conventional anchorage? Why are orthodontic mini-implants necessary? The development of the skeletal anchorage systems The biological basis for the skeletal anchorage systems...... The characteristics of the different skeletal anchorage systems The insertion procedure The indications for the use of orthodontic mini-implants Treatment planning in relation to the use of mini-implants Case presentations...

  7. Paradigm shifts in orthodontic treatment with mini-implant anchorage

    Directory of Open Access Journals (Sweden)

    Johnny Joung-Lin Liaw


    Full Text Available After the applications of mini-implant anchorage, the envelope of orthodontic treatment was expanded and some treatment modes were changed because of more predictable tooth movement with empowered anchorage. The author tried to share his experience of TADs applications for clarifying the paradigm shifts of orthodontic treatment assisted with the mini-implant anchorage.

  8. 76 FR 76295 - Anchorage Regulations; Wells, ME (United States)


    ... rule, call or email Mr. John J. Mauro, Waterways Management Branch Chief, First Coast Guard District; telephone (617) 223-8355, email . If you have questions on viewing or submitting... placed well within the anchorage areas so that no portion of the hull or rigging will at any time...

  9. Comparison of temporary anchorage devices and transpalatal arch-mediated anchorage reinforcement during canine retraction (United States)

    Kecik, Defne


    Objective: The purpose of this study was to compare the dental and skeletal effects of canine retraction using conventional anchorage reinforcement systems and comparing them with the usage of TADs. Materials and Methods: The sample consisted of 50 patients having Class I malocclusions with bimaxillary protrusion indicated for first premolar extraction, and allocated into two groups. The first group consisted of 25 patients with a mean age of 18,7 years (min:14, max:22 years, 16 girls and 9 boys) that TADs were applied as an anchorage mechanic between attached gingiva of upper second premolar and first molar teeth. The second group consisted of 25 patients with a mean age of 19,4 years (min:15, max:23 years, 14 girls and 11 boys) that conventional molar anchorage with Transpalatal arch (TPA) was applied for the anchorage mechanics against canine retraction. Results: The results showed that mean mesial movement and the tipping of the first molars in TAD group between T0 - T1 were insignificant (P > 0,05), however in the TPA group were significant (P0,05). Conclusion: Although TPA is a useful appliance, it doesn't provide an effective anchorage control on anteroposterior movement maxillary first molar teeth concerning first premolar extraction treatment. TADs are more convenient to provide absolute anchorage during maxillary canine retraction in contrast to transpalatal arch. PMID:28042267

  10. Polyamines regulate cell growth and cellular methylglyoxal in high-glucose medium independently of intracellular glutathione. (United States)

    Kwak, Min-Kyu; Lee, Mun-Hyoung; Park, Seong-Jun; Shin, Sang-Min; Liu, Rui; Kang, Sa-Ouk


    Polyamines can presumably inhibit protein glycation, when associated with the methylglyoxal inevitably produced during glycolysis. Herein, we hypothesized a nonenzymatic interaction between putrescine and methylglyoxal in putrescine-deficient or -overexpressing Dictyostelium cells in high-glucose medium, which can control methylglyoxal production. Putrescine was essentially required for growth rescue accompanying methylglyoxal detoxification when cells underwent growth defect and cell cycle G1-arrest when supplemented with high glucose. Furthermore, methylglyoxal regulation by putrescine seemed to be a parallel pathway independent of the changes in cellular glutathione content in high-glucose medium. Consequently, we suggest that Dictyostelium cells need polyamines for normal growth and cellular methylglyoxal regulation.

  11. Degree Growth, Linear Independence and Periods of a Class of Rational Dynamical Systems

    CERN Document Server

    Ostafe, Alina


    We introduce and study algebraic dynamical systems generated by triangular systems of rational functions. We obtain several results about the degree growth and linear independence of iterates as well as about possible lengths of trajectories generated by such dynamical systems over finite fields. Some of these results are generalisations of those known in the polynomial case, some are new even in this case.

  12. Procedures adopted by orthodontists for space closure and anchorage control

    Directory of Open Access Journals (Sweden)

    André da Costa Monini


    Full Text Available OBJECTIVE: The aim of this study was to identify the procedures adopted by Brazilian orthodontists in the following situations: extraction space closure, anchorage control in case of necessary anchorage for group A and frequency of skeletal anchorage use, especially in the upper jaw. METHOD: A questionnaire was sent to the e-mail address of all dentists registered in the Brazilian Federal Council of Dentistry. RESULTS: The results showed that most Brazilian orthodontists usually perform extraction space closure by means of sliding mechanics. The use of palatal bar, inclusion of second molars in the archwire and space closure performed in two phases are the most used techniques for anchorage control in the upper jaw. The skeletal anchorage is referenced by 36.5% of specialists as a routine practice for the upper jaw anchorage. CONCLUSIONS: There is a wide variety of procedures adopted by Brazilian orthodontists for orthodontic space closure and anchorage control.

  13. Francisella tularensis harvests nutrients derived via ATG5-independent autophagy to support intracellular growth.

    Directory of Open Access Journals (Sweden)

    Shaun Steele


    Full Text Available Francisella tularensis is a highly virulent intracellular pathogen that invades and replicates within numerous host cell types including macrophages, hepatocytes and pneumocytes. By 24 hours post invasion, F. tularensis replicates up to 1000-fold in the cytoplasm of infected cells. To achieve such rapid intracellular proliferation, F. tularensis must scavenge large quantities of essential carbon and energy sources from the host cell while evading anti-microbial immune responses. We found that macroautophagy, a eukaryotic cell process that primarily degrades host cell proteins and organelles as well as intracellular pathogens, was induced in F. tularensis infected cells. F. tularensis not only survived macroautophagy, but optimal intracellular bacterial growth was found to require macroautophagy. Intracellular growth upon macroautophagy inhibition was rescued by supplying excess nonessential amino acids or pyruvate, demonstrating that autophagy derived nutrients provide carbon and energy sources that support F. tularensis proliferation. Furthermore, F. tularensis did not require canonical, ATG5-dependent autophagy pathway induction but instead induced an ATG5-independent autophagy pathway. ATG5-independent autophagy induction caused the degradation of cellular constituents resulting in the release of nutrients that the bacteria harvested to support bacterial replication. Canonical macroautophagy limits the growth of several different bacterial species. However, our data demonstrate that ATG5-independent macroautophagy may be beneficial to some cytoplasmic bacteria by supplying nutrients to support bacterial growth.

  14. Measuring the democratic anchorage of governance networks

    DEFF Research Database (Denmark)

    Fotel, Trine; Sørensen, Eva; Torfing, Jacob

    in what we shall call a model for the democratic anchorage of governance networks. As illustrated by our qualitative case study of a multi-level and cross-border governance network involved in the recent decision to build a bridge between Denmark and Germany, the democratic anchorage model helps to assess......There has been a growing debate about the democratic problems and potentials of governance networks among political scientists and public managers. While some claim that governance networks tend to undermine democracy, others argue that they have the potential to improve and strengthen democracy....... This debate is found wanting in two respects. First of all, there has been far too little discussion about what democracy means in relation to pluricentric governance networks. Second, the current debate builds on the assumption that it is possible to give a clear-cut answer to the question of the democratic...

  15. Growth inhibiting effects of terazosin on androgen-independent prostate cancer cell lines

    Institute of Scientific and Technical Information of China (English)

    许克新; 王向红; 凌明达; 王云川


    Objective To study the effects of an α1-adrenoceptor antagonist, terazosin on the androgen-independent prostate cancer cell lines PC-3 and DU145.Methods Two androgen independent cell lines, PC-3 and DU145, were used to determine cell viability, colony-forming ability, as well as cell cycle distribution, after exposure to terazosin. Western blot analysis was used to determine the expression of p21WAF1 and p27KIP1.Results This study shows that terazosin inhibits not only prostate cancer cell growth but also its colony forming ability, both of which are main targets of clinical treatment. In addition, terazosin is shown to inhibit cell growth through G1 phase cell cycle arrest and the up-regulation of p27KIP1.Conclusion This study provides evidence that the α1-adrenoceptor antagonist terazosin may have therapeutic potential in the treatment of advanced hormone refractory prostate cancer.

  16. Role of Ca2+-independent phospholipase A2 in cell growth and signaling


    Hooks, Shelley B; Cummings, Brian S.


    Phospholipase A2(PLA2) are esterases that cleave glycerophospholipids to release fatty acids and lysophospholipids. Several studies demonstrate that PLA2 regulate growth and signaling in several cell types. However, few of these studies have focused on Ca2+-independent phospholipase A2(iPLA2 or Group VI PLA2). This class of PLA2 was originally suggested to mediate phospholipid remodeling in several cell types including macrophages. As such, it was labeled as a housekeeping protein and thought...

  17. Experimental evidence of pharmacological management of anchorage in Orthodontics: A systematic review (United States)

    Fernández-González, Felipe José; Cañigral, Aránzazu; Balbontín-Ayala, Felipe; Gonzalo-Orden, José Manuel; de Carlos, Felix; Cobo, Teresa; Fernández-Vázquez, Jose Pedro; Sánchez-Lasheras, Fernando; Vega, José Antonio


    Introduction: Orthodontic anchorage is one of the most challenging aspects of Orthodontics. Preventing undesired movement of teeth could result in safer and less complicated orthodontic treatment. Recently, several reviews have been published about the effects of different molecules on bone physiology and the clinical side effects in Orthodontics. However, the effects of local application of these substances on the rate of orthodontic tooth movement have not been assessed. Objectives: The aim of this research was to analyze the scientific evidence published in the literature about the effects of different molecules on orthodontic anchorage. Methods: The literature was systematically reviewed using PubMed/Medline, Scopus and Cochrane databases from 2000 up to July 31st, 2014. Articles were independently selected by two different researchers based on previously established inclusion and exclusion criteria, with a concordance Kappa index of 0.86. The methodological quality of the reviewed papers was performed. Results: Search strategy identified 270 articles. Twenty-five of them were selected after application of inclusion/exclusion criteria, and only 11 qualified for final analysis. Molecules involved in orthodontic anchorage were divided into three main groups: osteoprotegerin (OPG), bisphosphonates (BPs) and other molecules (OMs). Conclusions: Different drugs are able to alter the bone remodeling cycle, influencing osteoclast function and, therefore, tooth movement. Thus, they could be used in order to provide maximal anchorage while preventing undesired movements. OPG was found the most effective molecule in blocking the action of osteoclasts, thereby reducing undesired movements. PMID:26560822

  18. Dentoalveolar class III treatment using retromolar miniscrew anchorage

    National Research Council Canada - National Science Library

    Poletti, Laura; Silvera, Aimara A; Ghislanzoni, Luis T Huanca


    .... Conventional intraoral and extraoral appliances have many disadvantages, including the need for patient cooperation, potential for anchorage loss, and vertical extrusion of upper molars and lower incisors...

  19. Pumpkin seed extract: Cell growth inhibition of hyperplastic and cancer cells, independent of steroid hormone receptors. (United States)

    Medjakovic, Svjetlana; Hobiger, Stefanie; Ardjomand-Woelkart, Karin; Bucar, Franz; Jungbauer, Alois


    Pumpkin seeds have been known in folk medicine as remedy for kidney, bladder and prostate disorders since centuries. Nevertheless, pumpkin research provides insufficient data to back up traditional beliefs of ethnomedical practice. The bioactivity of a hydro-ethanolic extract of pumpkin seeds from the Styrian pumpkin, Cucurbita pepo L. subsp. pepo var. styriaca, was investigated. As pumpkin seed extracts are standardized to cucurbitin, this compound was also tested. Transactivational activity was evaluated for human androgen receptor, estrogen receptor and progesterone receptor with in vitro yeast assays. Cell viability tests with prostate cancer cells, breast cancer cells, colorectal adenocarcinoma cells and a hyperplastic cell line from benign prostate hyperplasia tissue were performed. As model for non-hyperplastic cells, effects on cell viability were tested with a human dermal fibroblast cell line (HDF-5). No transactivational activity was found for human androgen receptor, estrogen receptor and progesterone receptor, for both, extract and cucurbitin. A cell growth inhibition of ~40-50% was observed for all cell lines, with the exception of HDF-5, which showed with ~20% much lower cell growth inhibition. Given the receptor status of some cell lines, a steroid-hormone receptor independent growth inhibiting effect can be assumed. The cell growth inhibition for fast growing cells together with the cell growth inhibition of prostate-, breast- and colon cancer cells corroborates the ethnomedical use of pumpkin seeds for a treatment of benign prostate hyperplasia. Moreover, due to the lack of androgenic activity, pumpkin seed applications can be regarded as safe for the prostate.

  20. Role of Ca2+-independent phospholipase A2 in cell growth and signaling. (United States)

    Hooks, Shelley B; Cummings, Brian S


    Phospholipase A(2) (PLA(2)) are esterases that cleave glycerophospholipids to release fatty acids and lysophospholipids. Several studies demonstrate that PLA(2) regulate growth and signaling in several cell types. However, few of these studies have focused on Ca2+-independent phospholipase A(2) (iPLA(2) or Group VI PLA(2)). This class of PLA(2) was originally suggested to mediate phospholipid remodeling in several cell types including macrophages. As such, it was labeled as a housekeeping protein and thought not to play as significant of roles in cell growth as its older counterparts cytosolic PLA(2) (cPLA(2) or Group IV PLA(2)) and secretory PLA(2) (sPLA(2) or Groups I-III, V and IX-XIV PLA(2)). However, several recent studies demonstrate that iPLA(2) mediate cell growth, and do so by participating in signal transduction pathways that include epidermal growth factor receptors (EGFR), mitogen activated protein kinases (MAPK), mdm2, and even the tumor suppressor protein p53 and the cell cycle regulator p21. The exact mechanism by which iPLA(2) mediates these pathways are not known, but likely involve the generation of lipid signals such as arachidonic acid, lysophosphatidic acid (LPA) and lysophosphocholines (LPC). This review discusses the role of iPLA(2) in cell growth with special emphasis placed on their role in cell signaling. The putative lipid signals involved are also discussed.

  1. 76 FR 78185 - Anchorage Regulations: Subpart A-Special Anchorage Regulations, Newport Bay Harbor, CA (United States)

    2011-12-16 and will include any personal information you have provided. Submitting Comments If you submit a... would be incorporated into area A-11 under revised Sec. 110.95(k). An image of the proposed anchorage... rule under Executive Order 13045, Protection of Children from Environmental Health Risks and...

  2. Orthodontic treatment with skeletal anchorage system

    Directory of Open Access Journals (Sweden)

    Arya Brahmanta


    Full Text Available Background: Correction of class I malocclusion with bimaxillary dental protrusion and unilateral free end right upper ridge in adult patient is one of difficult biomechanical case in orthodontics. Due to this case that needs proper anchorage for upper incisor retraction with missing teeth in the right posterior segment. Purpose: The aim of this study to find an effective therapy for correction of bimaxillary protrusion with unilateral free and ridge. Case: A female patient, 36 year old complaining for the difficulty of lip closure due to severe bimaxillary protrusion with incompetence lip. Case management: Firstly correction of the maxillary and mandibular incisor proclination were done by extraction of the mandibular first premolar, the maxillary second premolar on left side and finally placement of miniplates implant in the zygomatic process on right side as an absolut anchorage. Conclusion: Skeletal anchorage system (SAS can be considered as an effective therapy for corection of bimaxillary protrusion with unilateral free end ridge.Latar belakang: Koreksi dari maloklusi klas I dari penderita dewasa yang disertai protrusi bimaksiler dengan kehilangan gigi posterior pada regio kanan atas merupakan salah satu kasus sulit untuk dikerjakan terutama berhubungan dengan biomekanik pergerakan giginya dalam perawatan ortodonti. Tujuan: Tujuan dari penulisan artikel ini adalah untuk menemukan terapi yang efektif untuk perbaikan protrusi bimaksiler dan kehilangan gigi posterior pada satu sisi. Kasus: Seorang penderita wanita usia 35 tahun datang dengan keluhan utama kesulitan untuk menutup mulut oleh karena gigi rahang atas dan rahang bawahnya maju dan bibirnya tidak kompeten. Tatalaksana kasus: Koreksi pada gigi insisivus rahang atas dan insisivus rahang bawah yang protrusi dilakukan dengan melakukan pencabutan terlebih dahulu pada gigi premolar pertama dirahang bawah sisi kanan dan sisi kiri serta pencabutan pada gigi premolar kedua di rahang atas sisi

  3. Impact of Growth Factor Independence 1 in Human T-Cell Lymphomas

    DEFF Research Database (Denmark)

    Dabrowska, Magdalena Julia; Dybkær, Karen; Johansen, Preben


    Impact of Growth Factor Independence 1 in Human T-Cell Lymphomas; Pathogenic Potential Identified by Insertional Mutagenesis in a Murine T-Cell Lymphoma Model. Magdalena Julia Dabrowska *,1, Karen Dybkaer *,1, Preben Johansen *,2, Hans Erik Johnsen1 and Finn Skou Pedersen *,3 1 Department...... role in the development of MLV induced lymphomas and strongly indicates that retroviral insertional mutagenesis in murine models of human NHLs can be used to identify new genes involved in lymphomagenesis and, by use of functional assays, their impact on human lymphomas can be evaluated. Disclosures...

  4. Shear and anchorage behaviour of fire exposed hollow core slabs

    NARCIS (Netherlands)

    Fellinger, J.H.H.; Stark, J.; Walraven, J.C.


    The fire resistance of hollow core slabs is currently assessed considering flexural failure only. However, fire tests showed that shear or anchorage failure can also govern the load bearing behaviour. As the shear and anchorage capacity of these slabs rely on the tensile strength of the concrete, th

  5. Mechanical anchorage of FRP tendons – A literature review

    DEFF Research Database (Denmark)

    Schmidt, Jacob W.; Bennitz, Anders; Täljsten, Björn


    anchorage systems for use with Aramid, Glass and Carbon FRP tendons have been proposed over the last two decades. Each system is usually tailored to a particular type of tendon. This paper presents a brief overview of bonded anchorage applications while the primary literature review discusses three methods...

  6. Anchorage of Main Reinforcement in Lightweight Aggregate Concrete Beams

    DEFF Research Database (Denmark)

    Larsen, Henning


    The paper deals with the anchorage of reinforcement bars at end supports in beam component made of lightweight aggregate concrete with open structure.......The paper deals with the anchorage of reinforcement bars at end supports in beam component made of lightweight aggregate concrete with open structure....

  7. 77 FR 54493 - Special Anchorage Area; Stockton Springs, ME (United States)


    ... Number USCG-2012-0172] RIN 1625-AA01 Special Anchorage Area; Stockton Springs, ME AGENCY: Coast Guard... anchorage area in Stockton Springs, Maine. This proposed action is necessary to facilitate safe navigation.... This action is intended to increase the safety of life and property in Stockton Springs, improve...

  8. 77 FR 22489 - Special Anchorage Regulations, Newport Bay Harbor, CA (United States)


    ... Master Plan Subcommittee of the City of Newport Harbor Commission led an outreach campaign involving a... meetings, the City of Newport asked the Coast Guard to amend its anchorage regulations. The Coast Guard... incorporated into area A-11 under revised Sec. 110.95(k). An image of the anchorage areas is available in...

  9. The Role of Platelet-Derived Growth Factor C and Its Splice Variant in Breast Cancer (United States)


    In addition, knockdown of PDGFC in MDA-MB-231 cells decreases anchorage independent growth as seen with soft-agar colony formation (Figure 4A...A structural superfamily of growth factors containing a cystine knot motif. Cell 73, 421 (May 7, 1993). 10. S. Rosenkranz, A. Kazlauskas, Evidence...shRNA. B. Soft Agar Colony formation C. WST-1 cell proliferation assay under normal serum containing conditions D. WST-1 cell proliferation assay

  10. Forced homo- and heterodimerization of all gp130-type receptor complexes leads to constitutive ligand-independent signaling and cytokine-independent growth. (United States)

    Suthaus, Jan; Tillmann, Anna; Lorenzen, Inken; Bulanova, Elena; Rose-John, Stefan; Scheller, Jürgen


    Naturally ligand independent constitutively active gp130 variants were described to be responsible for inflammatory hepatocellular adenomas. Recently, we genetically engineered a ligand-independent constitutively active gp130 variant based on homodimerization of Jun leucine zippers. Because also heterodimeric complexes within the gp130 family may have tumorigenic potential, we seek to generate ligand-independent constitutively active heterodimers for all known gp130-receptor complexes based on IL-15/IL-15R alpha-sushi fusion proteins. Ligand-independent heterodimerization of gp130 with WSX-1, LIFR, and OSMR and of OSMR with GPL led to constitutive, ligand-independent STAT1 and/or STAT3 and ERK1/2 phosphorylation. Moreover, these receptor combinations induced transcription of the STAT3 target genes c-myc and Pim-1 and factor-independent growth of stably transduced Ba/F3-gp130 cells. Here, we establish the IL-15/IL-15R alpha-sushi system as a new system to mimic constitutive and ligand-independent activation of homo- and heterodimeric receptor complexes, which might be applicable to other heterodimeric receptor families. A mutated IL-15 protein, which was still able to bind the IL-15R alpha-sushi domain, but not to beta- and gamma-receptor chains, in combination with the 2A peptide technology may be used to translate our in vitro data into the in vivo situation to assess the tumorigenic potential of gp130-heterodimeric receptor complexes.

  11. FBXW7 Acts as an Independent Prognostic Marker and Inhibits Tumor Growth in Human Osteosarcoma

    Directory of Open Access Journals (Sweden)

    Zhanchun Li


    Full Text Available F-box and WD repeat domain-containing 7 (FBXW7 is a potent tumor suppressor in human cancers including breast cancer, colorectal cancer, gastric cancer and hepatocellular carcinoma. In this study, we found that the expressions of FBXW7 protein and mRNA levels in osteosarcoma (OS cases were significantly lower than those in normal bone tissues. Clinical analysis indicated that FBXW7 was expressed at lower levels in OS patients with advanced clinical stage, high T classification and poor histological differentiation. Furthermore, we demonstrated that high expression of FBXW7 was correlated with a better 5-year survival of OS patients. Multivariate Cox regression analysis indicated that FBXW7 was an independent prognostic marker in OS. Our in vitro studies showed that FBXW7 overexpression inhibited cell cycle transition and cell proliferation, and promoted apoptosis in both U2OS and MG-63 cells. In a nude mouse xenograft model, FBXW7 overexpression slowed down tumor growth by inducing apoptosis and growth arrest. Mechanistically, FBXW7 inversely regulated oncoprotein c-Myc and cyclin E levels in both U2OS and MG-63 cells. Together these findings suggest that FBXW7 may serve as a prognostic biomarker and inhibit tumor progression by inducing apoptosis and growth arrest in OS.

  12. Arabidopsis growth under prolonged high temperature and water deficit: independent or interactive effects? (United States)

    Vile, Denis; Pervent, Marjorie; Belluau, Michaël; Vasseur, François; Bresson, Justine; Muller, Bertrand; Granier, Christine; Simonneau, Thierry


    High temperature (HT) and water deficit (WD) are frequent environmental constraints restricting plant growth and productivity. These stresses often occur simultaneously in the field, but little is known about their combined impacts on plant growth, development and physiology. We evaluated the responses of 10 Arabidopsis thaliana natural accessions to prolonged elevated air temperature (30 °C) and soil WD applied separately or in combination. Plant growth was significantly reduced under both stresses and their combination was even more detrimental to plant performance. The effects of the two stresses were globally additive, but some traits responded specifically to one but not the other stress. Root allocation increased in response to WD, while reproductive allocation, hyponasty and specific leaf area increased under HT. All the traits that varied in response to combined stresses also responded to at least one of them. Tolerance to WD was higher in small-sized accessions under control temperature and HT and in accessions with high biomass allocation to root under control conditions. Accessions that originate from sites with higher temperature have less stomatal density and allocate less biomass to the roots when cultivated under HT. Independence and interaction between stresses as well as the relationships between traits and stress responses are discussed.

  13. Explaining the democratic anchorage of governance networks

    DEFF Research Database (Denmark)

    Skelcher, Chris; Klijn, Erik-Hans; Kübler, Daniel


    Advances in understanding the democratic anchorage of governance networks require carefully designed and contextually grounded empirical analysis that take into account contextual factors. The article uses a conjectural framework to study the impact of the national democratic milieu...... on the relationship between network governance and representative institutions in four European countries: the United Kingdom, Switzerland, the Netherlands, and Denmark. The article shows that the distinction between majoritarian and consensus democracy as well as the varying strength of voluntary associations...... are important contextual factors that help explain cross-national differences in the relationship between governance networks and representative institutions. We conclude that a context of weak associationalism in majoritarian democracies facilitates the instrumentalization of networks by government actors...

  14. Deformation tests and failure process analysis of an anchorage structure

    Institute of Scientific and Technical Information of China (English)

    Zhao Tongbin; Yin Yanchun; Tan Yunliang; Song Yimin


    In order to study the failure process of an anchorage structure and the evolution law of the body’s defor-mation field, anchor push-out tests were carried out based on digital speckle correlation methods (DSCM). The stress distribution of the anchorage interface was investigated using the particle flow numerical simulation method. The results indicate that there are three stages in the deformation and fail-ure process of an anchorage structure:elastic bonding stage, a de-bonding stage and a failure stage. The stress distribution in the interface controls the stability of the structure. In the elastic bonding stage, the shear stress peak point of the interface is close to the loading end, and the displacement field gradually develops into a ‘V’ shape. In the de-bonding stage, there is a shear stress plateau in the center of the anchorage section, and shear strain localization begins to form in the deformation field. In the failure stage, the bonding of the interface fails rapidly and the shear stress peak point moves to the anchorage free end. The anchorage structure moves integrally along the macro-crack. The de-bonding stage is a research focus in the deformation and failure process of an anchorage structure, and plays an important guiding role in roadway support design and prediction of the stability of the surrounding rock.

  15. The benefit of differential moment concept in managing posterior anchorage and avoiding bite deepening

    Directory of Open Access Journals (Sweden)

    Harryanto Wijaya


    Full Text Available Background: Anchorage is one of the major concerns in orthodontic space closure. Various methods have been proposed to enhance posterior anchorage in space closure such as headgear, Nance holding appliance, and micro implant as temporary anchorage devices. However, several issues such as patient's compliance, appliance effectiveness, and cost of the device become many clinicians concern. The differential moment concept in segmented arch is a technique that requires no patient compliance but can effectively manage posterior anchorage and avoid bite deepening by careful application of forces and moments. Purpose: The purpose of this case report is to show the use of differential moment concept in segmented arch technique to manage posterior anchorage and to avoid bite deepening. Case: A 21 years old female patient with protrusive teeth as her chief complaint was treated using fixed orthodontic appliance. Case management: The treatment included four first bicuspid extraction and space closure utilizing differential moment concept in segmented arch. Conclusion: It can be concluded that application of differential moment concept in segmented arch technique is a non invasive, compliance independent, effective, and cost efficient method to manage posterior anchorage and to avoid bite deepening.latar belakang: Penjangkaran merupakan salah satu aspek yang sering kali menjadi masalah dalam penutupan ruang pada perawatan ortodonti. Berbagai metode disarankan untuk memperkuat penjangkaran posterior dalam penutupan ruang seperti headgear, piranti penahan Nance, dan implan mikro sebagai alat penjangkar sementara. Namun demikian, beberapa hal seperti kerjasama pasien, efektivitas piranti, dan biaya dari alat-alat tersebut sering menjadi perhatian/pertimbangan bagi klinisi. Konsep momen diferensial pada segmented arch adalah suatu cara yang efektif untuk memperkuat penjangkaran dan menghindari pendalaman gigitan tanpa memerlukan kerjasama pasien. tujuan

  16. Neuropilin-1 mediates vascular permeability independently of vascular endothelial growth factor receptor-2 activation. (United States)

    Roth, Lise; Prahst, Claudia; Ruckdeschel, Tina; Savant, Soniya; Weström, Simone; Fantin, Alessandro; Riedel, Maria; Héroult, Mélanie; Ruhrberg, Christiana; Augustin, Hellmut G


    Neuropilin-1 (NRP1) regulates developmental and pathological angiogenesis, arteriogenesis, and vascular permeability, acting as a coreceptor for semaphorin 3A (Sema3A) and the 165-amino acid isoform of vascular endothelial growth factor A (VEGF-A165). NRP1 is also the receptor for the CendR peptides, a class of cell- and tissue-penetrating peptides with a specific R-x-x-R carboxyl-terminal motif. Because the cytoplasmic domain of NRP1 lacks catalytic activity, NRP1 is mainly thought to act through the recruitment and binding to other receptors. We report here that the NRP1 intracellular domain mediates vascular permeability. Stimulation with VEGF-A165, a ligand-blocking antibody, and a CendR peptide led to NRP1 accumulation at cell-cell contacts in endothelial cell monolayers, increased cellular permeability in vitro and vascular leakage in vivo. Biochemical analyses, VEGF receptor-2 (VEGFR-2) silencing, and the use of a specific VEGFR blocker established that the effects induced by the CendR peptide and the antibody were independent of VEGFR-2. Moreover, leakage assays in mice expressing a mutant NRP1 lacking the cytoplasmic domain revealed that this domain was required for NRP1-induced vascular permeability in vivo. Hence, these data define a vascular permeability pathway mediated by NRP1 but independent of VEGFR-2 activation.

  17. Trailing or paradoxical growth of Aspergillus flavus exposed to caspofungin is independent of genotype. (United States)

    Hadrich, Inès; Neji, Sourour; Makni, Fattouma; Ayadi, Ali; Elloumi, Moez; Ranque, Stéphane


    There are limited data on in vitro susceptibility testing of echinocandins against Aspergillus species. The objective of this study was to describe the phenotypes of Aspergillus flavus observed on exposure to caspofungin in vitro and to test whether these phenotypes were associated with A. flavus genotypes. The caspofungin MICs of 37 A. flavus clinical isolates collected from 14 patients with invasive aspergillosis were determined using Etest assays. Caspofungin MICs ranged from 0.012 to 0.064 mg l(-1); the modal MIC was 0.023 mg l(-1) and the MIC₅₀ and MIC₉₀ were 0.032 and 0.064 mg l(-1), respectively. A clear end point was noted in 24 (65 %) isolates, whereas seven (19 %) displayed a trailing effect and six (16 %) showed paradoxical growth when exposed to caspofungin. In these A. flavus isolates, the absence of a significant population structure or genetic differentiation indicated that trailing or paradoxical growth phenotypes were independent of microsatellite genotype.

  18. Comparative evaluation of anchorage reinforcement between orthodontic implants and conventional anchorage in orthodontic management of bimaxillary dentoalveolar protrusion. (United States)

    Chopra, S S; Mukherjee, Manish; Mitra, Rajat; Kochar, Gagan Deep; Kadu, Abhijeet


    Increased upper lip procumbency is commonly associated with maxillary dentoalveolar protrusion with the major goal of reducing maxillary dentoalveolar protrusion. The treatment plan usually includes extraction of the maxillary first premolars, followed by retraction of anterior teeth with maximum anchorage. Dental implants have been widely accepted as successful adjuncts for obtaining maximum anchorage in orthodontic treatment. 50 subjects between the ages of 13 and 17 years having bimaxillary dentoalveolar protrusion were included in the study. The patients were divided into two groups. Both groups received treatment with 0.022″ MBT prescription preadjusted edgewise appliance system. In addition, subjects of Group 'I' received the Nance button and lingual arch as anchorage reinforcement in the upper and lower arches, respectively. Subjects of Group 'II' received self-drilling titanium OI for anchorage reinforcement. Significant retraction was achieved in all cases with good vertical control. Anchor loss was observed in both groups. Anchor loss was much higher in Group I compared to Group II, and an intergroup comparison for anchor loss was highly significant. Implants as anchorage, for en masse retraction, can be incorporated into orthodontic practice. The use of orthodontic implants for anchorage is a viable alternative to conventional molar anchorage.

  19. Minor tooth movements using microimplant anchorage: case reports. (United States)

    Sohn, Dong-Seok; Lee, Jung-Kwang; An, Kyung-Mi


    For the treatment of extruded or tipped molars, various conventional techniques have been used. But those methods may lead to undesirable movement of the anchorage units and lengthen treatment time because of limited tooth-borne anchorage potential. Introduction of microimplants as orthodontic anchorage has expanded treatment possibilities because of their advantages. Some advantages are a less complex surgical procedure, decrease in cost, immediate loading, and their ability to be placed in any area of the alveolar bone. This article will illustrate clinical experiences in patients who were treated with the intrusion of overerupted molars, the up-righting of tilted molars, and other clinical applications for minor tooth movements. Anchorage control was achieved with the surgical insertion of titanium microimplants for immediate loading in the alveolar bone. When needed, minimal fixed appliances were used and orthodontic treatment was completed without any other complications.

  20. Urban contaminants project: Fish and Hood Creeks, Anchorage, Alaska (United States)

    US Fish and Wildlife Service, Department of the Interior — Urbanization has decreased water quality and adversely impacted biological communities in the lakes and streams of Anchorage, Alaska (Hock, 1981; Brabets, 1987;...

  1. Application and Curative Effect of Micro-implant Anchorage in ...

    African Journals Online (AJOL)

    in the treatment group were treated with a micro-implant as the anchorage, while 31 cases of the .... prescribedan oral antibiotic in case of infection ... removed. Local infiltration anesthesia was unnecessary and the wound would heal in a.

  2. 75 FR 3641 - Television Broadcasting Services; Anchorage, AK (United States)


    ... From the Federal Register Online via the Government Publishing Office FEDERAL COMMUNICATIONS COMMISSION 47 CFR Part 73 Television Broadcasting Services; Anchorage, AK AGENCY: Federal Communications... broadcasting. 0 For the reasons discussed in the preamble, the Federal Communications Commission amends 47...

  3. Essix retainer as a modified esthetic anchorage device

    Directory of Open Access Journals (Sweden)

    Kamlesh Kumar Garg


    Full Text Available Essix based appliances have multiple uses in orthodontics, which greatly expand the many treatment options currently available. In office fabrication presents an additional asset and because Essix appliances are clear plastic, the result is esthetically pleasing to the eye. The current case report introduces a novel technique of correcting individual tooth rotations using Essix based anchorage appliance in patients with limited anchorage options because of missing teeth or severe crowding.

  4. Induction of p53-independent growth inhibition in lung carcinoma cell A549 by gypenosides (United States)

    Liu, Jung-Sen; Chiang, Tzu-Hsuan; Wang, Jinn-Shyan; Lin, Li-Ju; Chao, Wei-Chih; Inbaraj, Baskaran Stephen; Lu, Jyh-Feng; Chen, Bing-Huei


    The objectives of this study are to investigate antiproliferative effect and mechanisms of bioactive compounds from Gynostemma pentaphyllum (G. pentaphyllum) on lung carcinoma cell A549. Saponins, carotenoids and chlorophylls were extracted and fractionated by column chromatography, and were subjected to high-performance liquid chromatography-mass spectrometry analyses. The saponin fraction, which consisted mainly of gypenoside (Gyp) XXII and XXIII, rather than the carotenoid and chlorophyll ones, was effective in inhibiting A549 cell growth in a concentration- and a time-dependent manner as evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The estimated half maximal inhibitory concentration (IC50) of Gyp on A549 cells was 30.6 μg/ml. Gyp was further demonstrated to induce an apparent arrest of the A549 cell cycle at both the S phase and the G2/M phase, accompanied by a concentration- and a time-dependent increase in the proportions of both the early and late apoptotic cells. Furthermore, Gyp down-regulated cellular expression of cyclin A and B as well as BCL-2, while up-regulated the expression of BAX, DNA degradation factor 35 KD, poly [ADP-ribose] polymerase 1, p53, p21 and caspase-3. Nevertheless, both the treatment of a p53 inhibitor, pifithrin-α, and the small hairpin RNA-mediated p53 knockdown in the A549 cells did not alter the growth inhibition effect induced by Gyp. As a result, the cell cycle arrest and apoptosis of A549 cells induced by Gyp would most likely proceed through p53-independent pathway(s). PMID:25781909

  5. Antisense EGFR sequence reverses the growth properties of human liver carcinoma cell line BEL-7404 in vitro

    Institute of Scientific and Technical Information of China (English)



    A recombinant plasmid containing a full length human epidermal growth factor receptor (EGFR) cDNA sequence in antisense orientation was transferred into cells of a human liver carcinoma cell line BEL-7404. Compared with the control cell clone JX-0 transferred with the vector plasmid and the parent BEL-7404 cells, the antisense EGFR transferred cell clone JX-1 showed a decreased EGFR gene expression and reduced significantly the growth potential either in anchorage-dependent or anchorage-independent growth. Furthermore. JX-1 cells appeared to be distinctly dependent on serum concentration for monolayer growth. The results suggested that antisense EGFR could partly block the EGFR gene ex-pression and reverse the malignant growth properties of human liver carcinoma cells in vitro.

  6. Growth independent rhamnolipid production from glucose using the non-pathogenic Pseudomonas putida KT2440

    Directory of Open Access Journals (Sweden)

    Wittgens Andreas


    Full Text Available Abstract Background Rhamnolipids are potent biosurfactants with high potential for industrial applications. However, rhamnolipids are currently produced with the opportunistic pathogen Pseudomonas aeruginosa during growth on hydrophobic substrates such as plant oils. The heterologous production of rhamnolipids entails two essential advantages: Disconnecting the rhamnolipid biosynthesis from the complex quorum sensing regulation and the opportunity of avoiding pathogenic production strains, in particular P. aeruginosa. In addition, separation of rhamnolipids from fatty acids is difficult and hence costly. Results Here, the metabolic engineering of a rhamnolipid producing Pseudomonas putida KT2440, a strain certified as safety strain using glucose as carbon source to avoid cumbersome product purification, is reported. Notably, P. putida KT2440 features almost no changes in growth rate and lag-phase in the presence of high concentrations of rhamnolipids (> 90 g/L in contrast to the industrially important bacteria Bacillus subtilis, Corynebacterium glutamicum, and Escherichia coli. P. putida KT2440 expressing the rhlAB-genes from P. aeruginosa PAO1 produces mono-rhamnolipids of P. aeruginosa PAO1 type (mainly C10:C10. The metabolic network was optimized in silico for rhamnolipid synthesis from glucose. In addition, a first genetic optimization, the removal of polyhydroxyalkanoate formation as competing pathway, was implemented. The final strain had production rates in the range of P. aeruginosa PAO1 at yields of about 0.15 g/gglucose corresponding to 32% of the theoretical optimum. What's more, rhamnolipid production was independent from biomass formation, a trait that can be exploited for high rhamnolipid production without high biomass formation. Conclusions A functional alternative to the pathogenic rhamnolipid producer P. aeruginosa was constructed and characterized. P. putida KT24C1 pVLT31_rhlAB featured the highest yield and titer reported

  7. Increased linear bone growth by GH in the absence of SOCS2 is independent of IGF-1. (United States)

    Dobie, Ross; Ahmed, Syed F; Staines, Katherine A; Pass, Chloe; Jasim, Seema; MacRae, Vicky E; Farquharson, Colin


    Growth hormone (GH) signaling is essential for postnatal linear bone growth, but the relative importance of GHs actions on the liver and/or growth plate cartilage remains unclear. The importance of liver derived insulin like-growth factor-1 (IGF-1) for endochondral growth has recently been challenged. Here, we investigate linear growth in Suppressor of Cytokine Signaling-2 (SOCS2) knockout mice, which have enhanced growth despite normal systemic GH/IGF-1 levels. Wild-type embryonic ex vivo metatarsals failed to exhibit increased linear growth in response to GH, but displayed increased Socs2 transcript levels (P GH treatment enhanced metatarsal linear growth over a 12 day period. Despite this increase, IGF-1 transcript and protein levels were not increased in response to GH. In accordance with these data, IGF-1 levels were unchanged in GH-challenged postnatal Socs2(-/-) conditioned medium despite metatarsals showing enhanced linear growth. Growth-plate Igf1 mRNA levels were not elevated in juvenile Socs2(-/-) mice. GH did however elevate IGF-binding protein 3 levels in conditioned medium from GH challenged metatarsals and this was more apparent in Socs2(-/-) metatarsals. GH did not enhance the growth of Socs2(-/-) metatarsals when the IGF receptor was inhibited, suggesting that IGF receptor mediated mechanisms are required. IGF-2 may be responsible as IGF-2 promoted metatarsal growth and Igf2 expression was elevated in Socs2(-/-) (but not WT) metatarsals in response to GH. These studies emphasise the critical importance of SOCS2 in regulating GHs ability to promote bone growth. Also, GH appears to act directly on the metatarsals of Socs2(-/-) mice, promoting growth via a mechanism that is independent of IGF-1.

  8. On the origin of size-dependent and size-independent crystal growth: Influence of advection and diffusion (United States)

    Kile, D.E.; Eberl, D.D.


    Crystal growth experiments were conducted using potassium alum and calcite crystals in aqueous solution under both non-stirred and stirred conditions to elucidate the mechanism for size-dependent (proportionate) and size-independent (constant) crystal growth. Growth by these two laws can be distinguished from each other because the relative size difference among crystals is maintained during proportionate growth, leading to a constant crystal size variance (??2) for a crystal size distribution (CSD) as the mean size increases. The absolute size difference among crystals is maintained during constant growth, resulting in a decrease in size variance. Results of these experiments show that for centimeter-sized alum crystals, proportionate growth occurs in stirred systems, whereas constant growth occurs in non-stirred systems. Accordingly, the mechanism for proportionate growth is hypothesized to be related to the supply of reactants to the crystal surface by advection, whereas constant growth is related to supply by diffusion. Paradoxically, micrometer-sized calcite crystals showed proportionate growth both in stirred and in non-stirred systems. Such growth presumably results from the effects of convection and Brownian motion, which promote an advective environment and hence proportionate growth for minute crystals in non-stirred systems, thereby indicating the importance of solution velocity relative to crystal size. Calcite crystals grown in gels, where fluid motion was minimized, showed evidence for constant, diffusion-controlled growth. Additional investigations of CSDs of naturally occurring crystals indicate that proportionate growth is by far the most common growth law, thereby suggesting that advection, rather than diffusion, is the dominant process for supplying reactants to crystal surfaces.

  9. The low levels of circulating hepatocyte growth factor in nephrolithiasis cases: independent from gene polymorphism. (United States)

    Ozturk, Nurinnisa; Aksoy, Hulya; Aksoy, Yilmaz; Yildirim, Abdulkadir; Akcay, Fatih; Yanmaz, Vefa


    Environmental and genetic factors are important in development of nephrolithiasis. In a recent study, it has been demonstrated that hepatocyte growth factor (HGF) has an anti-apoptotic effect and thus can reduce the adhesion of calcium oxalate monohydrate crystals to renal epithelial cells. The aim of this study was to evaluate the HGF serum levels and its two gene polymorphisms and possible association of the two in patients with nephrolithiasis. One hundred and five patients with nephrolithiasis and 70 healthy volunteers with similar demographic features were included in this study. Serum HGF levels were measured, and HGF intron 13 C>A (in 102 stone patients and 68 healthy subjects) and intron 14 T>C (in 99 stone patients and 56 healthy subjects) polymorphisms were determined using real-time polymerase chain reaction with TaqMan allelic discrimination method. There were no statistically significant differences in HGF intron 13 C>A and intron 14 T>C polymorphisms between the control and patient groups (X (2) = 1.72 df = 2; p = 0.42, and X (2) = 0.68 df = 2; p = 0.71, respectively). Mean serum HGF concentration was significantly lower in the stone disease patients than in the control subjects (1.05 ± 0.63 pg/mL and 1.35 ± 0.58 ng/mL respectively, p = 0.0001). When allele distribution frequency between stone patients and healthy subjects was compared, there were no significant differences in intron 13 and intron 14 allele distributions between two groups (p = 0.43 and p = 0.44, respectively). It may be concluded from the findings that decrease in HGF levels may play a role in renal stone formation, independent from gene polymorphisms.

  10. Prevalence of the use of anchorage miniscrews among French orthodontists. (United States)

    Barthelemi, Stéphane; Beauval, Hélène


    Since always, anchorage has raised frequent problems for orthodontists. Since the early 2000s, the use of anchorage miniscrews has spread on a vast scale among practitioners. For the first time, a broad epidemiological survey (733 exploitable responses) has looked into the habits of French orthodontists regarding the use of anchorage miniscrews. The survey reveals that the majority of French practitioners have adopted miniscrews in their daily practice (66%), particularly among those using the lingual technique. However, the number of patients concerned still remains small for most practitioners (fewer than 10 patients for 65% of users). Seventy-four percent of users are satisfied with their experience with miniscrews although a majority uses them exclusively in adults (64%). The movements most sought by miniscrew users are mesialization/distalization and intrusion/extrusion. Among non-users, 60% have never placed an anchorage miniscrew but are thinking about doing so, whereas 20% of practitioners have used them but have since abandoned them. Finally, 20% of non-users have never used anchorage miniscrews and do not intend to do so.

  11. Purification of autocrine growth factor from conditioned medium of rat sarcoma (XC) cells. (United States)

    Checiówna, D; Klein, A


    Transformation of rat cells by Rous sarcoma virus(es) induced the release of growth factors into serum-free conditioned media. An PR-RSV-transformed rat cell line, XC, produced and released polypeptide factors which promote anchorage-dependent and anchorage-independent growth of XC cells. One of the autocrine factors of XC cells was purified to homogeneity by four-step procedure: ultrafiltration, ion-exchange chromatography on MonoS, reverse-phase chromatography on Spherisorb ODS2 and gel filtration on Superose 12. The factor gave a single band on SDS-electrophoresis on polyacrylamide gel and was assumed to have a molecular weight of 16 kDa. The factor is a potent mitogen for XC cells; half-maximal stimulation of DNA synthesis was achieved at a concentration of 0.8 ng/ml. The peptide is probably one of the family of EGF-like heparin-binding growth factors.

  12. FRP tendon anchorage in post-tensioned concrete structures

    DEFF Research Database (Denmark)

    Schmidt, Jacob Wittrup; Täljsten, Björn; Bennitz, Anders


    Strengthening of building structures by the use of various external post-tensioning steel tendon systems, is known to be a very efficient method. However, FRP as material in external post-tensioning projects has been investigated during the last decade. The advantages for this material are the high...... effective Young´s modulus and the high stress capacity in the linear elastic range of the material. The use of external tendons increases the requirements on the anchorage systems. This is in particular important when using un-bonded tendon systems, where the anchorage and deviators are the only force...... transfer points. The demand for high capacity anchorage tendons is fulfilled for steel tendons, but no competitive mechanical anchor has yet been developed for FRP tendon. A new small, reliable and more user friendly anchor has to be developed, before FRP tendons can be utilized with all of its capacity...

  13. Clinical applications of orthodontic microimplant anchorage in craniofacial patients. (United States)

    Vachiramon, Amornpong; Urata, Mark; Kyung, Hee Moon; Yamashita, Dennis-Duke; Yen, Stephen L-K


    Microimplant anchors, also known as temporary anchorage devices, mini- and micro-screws, have been used to enhance orthodontic anchorage for difficult tooth movements. Here, the authors describe how microimplants can be used to help treat craniofacial patients by supporting distraction osteogenesis procedures, maxillary protraction procedures, cleft segment expansion and stabilization, and tooth movement into narrow alveolar cleft sites. While most craniofacial patients are treated without microimplants, it would be worthwhile to identify which cases could benefit from microimplant anchorage. As an adjunct to orthodontic treatment, the microimplant offers a potential method for solving troublesome orthodontic and surgical problems such as guiding distraction procedures with orthodontics when primary teeth are exfoliating, addressing residual maxillary cants after vertical distraction osteogenesis of a ramus, stabilizing an edentulous premaxilla, and moving teeth into atrophic alveolar ridges. These cases are presented to open a dialogue on their possible uses in craniofacial patients.

  14. On the biomechanics of seedling anchorage (United States)

    Crouzy, Benoît; Edmaier, Katharina; Perona, Paolo


    We propose a minimal model for the response of vegetation to pullout constraints at early development stage. We try to capture both the average mechanical properties of the root system and the stochastic component of the uprooting process of seedlings. We identify a minimal set of relevant physical components in the purpose of quantifying the uprooting process: length of the root fibres, elastic response of the fibres and adhesion between the roots and the soil matrix. We present for validation a dataset extracted from Edmaier et al. (under revision), accounting for 98 uprooting experiments using Avena sativa L. seedlings (common oat), growing in non-cohesive sediment under controlled conditions. The corresponding root system has a very simple architecture, with three root fibres of different lengths. The response of the system to the constraint is however complex: the stress-strain signal presents sudden jumps followed by partial elastic recoveries. The analysis of the jumps and partial recoveries gives an insight into the resilience of the system. The anchorage of less mature seedlings rapidly collapses after the peak force has been reached, while more mature seedlings usually recover from partial failures. We explore this crossover with our validation dataset. The type of seedlings we study has been used in flume experiments investigating the feedbacks between the vegetation and the river morphodynamics (see for example Perona et al. (2012)). An understanding of the characteristics of the uprooting curve (maximal uprooting force and total uprooting work) of such vegetation reveals the ability of seedlings to withstand environmental constraints in terms of duration or intensity (see Edmaier et al., under revision), and is therefore helpful for planning future experiments. REFERENCES - P. Perona, P. Molnar, B. Crouzy, E. Perucca, Z. Jiang, S. McLelland, D. Wüthrich, K. Edmaier, R. Francis, C. Camporeale, et al., Biomass selection by floods and related timescales

  15. Growth hormone promotes skeletal muscle cell fusion independent of insulin-like growth factor 1 up-regulation


    Sotiropoulos, Athanassia; Ohanna, Mickaël; Kedzia, Cécile; Menon, Ram K.; Kopchick, John J.; Kelly, Paul A; Pende, Mario


    Growth hormone (GH) participates in the postnatal regulation of skeletal muscle growth, although the mechanism of action is unclear. Here we show that the mass of skeletal muscles lacking GH receptors is reduced because of a decrease in myofiber size with normal myofiber number. GH signaling controls the size of the differentiated myotubes in a cell-autonomous manner while having no effect on size, proliferation, and differentiation of the myoblast precursor cells. The GH hypertrophic action ...

  16. Phosphoproteome analysis demonstrates the potential role of THRAP3 phosphorylation in androgen-independent prostate cancer cell growth. (United States)

    Ino, Yoko; Arakawa, Noriaki; Ishiguro, Hitoshi; Uemura, Hiroji; Kubota, Yoshinobu; Hirano, Hisashi; Toda, Tosifusa


    Elucidating the androgen-independent growth mechanism is critical for developing effective treatment strategies to combat androgen-independent prostate cancer. We performed a comparative phosphoproteome analysis using a prostate cancer cell line, LNCaP, and an LNCaP-derived androgen-independent cell line, LNCaP-AI, to identify phosphoproteins involved in this mechanism. We performed quantitative comparisons of the phosphopeptide levels in tryptic digests of protein extracts from these cell lines using MS. We found that the levels of 69 phosphopeptides in 66 proteins significantly differed between LNCaP and LNCaP-AI. In particular, we focused on thyroid hormone receptor associated protein 3 (THRAP3), which is a known transcriptional coactivator of the androgen receptor. The phosphorylation level of THRAP3 was significantly lower at S248 and S253 in LNCaP-AI cells. Furthermore, pull-down assays showed that 32 proteins uniquely bound to the nonphosphorylatable mutant form of THRAP3, whereas 31 other proteins uniquely bound to the phosphorylation-mimic form. Many of the differentially interacting proteins were identified as being involved with RNA splicing and processing. These results suggest that the phosphorylation state of THRAP3 at S248 and S253 might be involved in the mechanism of androgen-independent prostate cancer cell growth by changing the interaction partners.

  17. Acetylsalicylic acid interferes with embryonic kidney growth and development by a prostaglandin-independent mechanism. (United States)

    Welham, Simon J M; Sparrow, Alexander J; Gardner, David S; Elmes, Matthew J


    To evaluate the effects of the non-selective, non-steroidal anti-inflammatory drug (NSAID) acetylsalicylic acid (ASA), on ex vivo embryonic kidney growth and development. Pairs of fetal mouse kidneys at embryonic day 12.5 were cultured ex vivo in increasing concentrations of ASA (0.04-0.4 mg/mL) for up to 7 d. One organ from each pair was grown in control media and was used as the internal control for the experimental contralateral organ. In some experiments, organs were treated with ASA for 48 h and then transferred either to control media alone or control media containing 10 μmol/L prostaglandin E2 (PGE2) for a further 5 d. Fetal kidneys were additionally obtained from prostaglandin synthase 2 homozygous null or heterozygous (PTGS2(-/-) and PTGS2(-/+)) embryos and grown in culture. Kidney cross-sectional area was used to determine treatment effects on kidney growth. Whole-mount labelling to fluorescently detect laminin enabled crude determination of epithelial branching using confocal microscopy. Increasing ASA concentration (0.1, 0.2 and 0.4 mg/mL) significantly inhibited metanephric growth (P growth area to control levels. Application of control media alone after cessation of ASA exposure showed no benefit on kidney growth. Despite the apparent recovery of growth area with 10 μmol/L PGE2, no obvious renal tubular structures were formed. The number of epithelial tips generated after 48 h exposure to ASA was reduced by 40% (0.2 mg/mL; P growth of PTGS2(-/-) and PTGS2(+/-) kidneys in organ culture showed no differences, indicating that PTGS2 derived PGE2 may at best have a minor role. ASA reduces early renal growth and development but the role of prostaglandins in this may be minor.

  18. Shear and anchorage behaviour of fire exposed hollow core slabs

    NARCIS (Netherlands)

    Fellinger, J.


    The fire resistance of hollow core slabs is currently assessed considering flexural failure only. However, fire tests show that shear or anchorage failure can also govern the load bearing behaviour. This paper is based on the dissertation by the author1 and discusses existing and new fire tests. It

  19. Shear and Anchorage Behaviour of Fire Exposed Hollow Core Slabs

    NARCIS (Netherlands)

    Fellinger, J.H.H.


    Hollow core (HC) slabs are made of precast concrete with pretensioned strands. These slabs are popular as floor structures in offices and housing. At ambient conditions, the load bearing capacity can be dominated by four different failure modes, i.e. flexure, anchorage, shear compression and shear t

  20. Shear and Anchorage Behaviour of Fire Exposed Hollow Core Slabs

    NARCIS (Netherlands)

    Fellinger, J.H.H.


    Hollow core (HC) slabs are made of precast concrete with pretensioned strands. These slabs are popular as floor structures in offices and housing. At ambient conditions, the load bearing capacity can be dominated by four different failure modes, i.e. flexure, anchorage, shear compression and shear

  1. Anchorage Behaviors of Frictional Tieback Anchors in Silty Sand (United States)

    Hsu, Shih-Tsung; Hsiao, Wen-Ta; Chen, Ke-Ting; Hu, Wen-Chi; Wu, Ssu-Yi


    Soil anchors are extensively used in geotechnical applications, most commonly serve as tieback walls in deep excavations. To investigate the anchorage mechanisms of this tieback anchor, a constitutive model that considers both strain hardening and softening and volume dilatancy entitled SHASOVOD model, and FLAC3D software are used to perform 3-D numerical analyses. The results from field anchor tests are compared with those calculated by numerical analyses to enhance the applicability of the numerical method. After the calibration, this research carried out the parameter studies by numerical analyses. The numerical results reveal that whether the yield of soil around an anchor develops to ground surface and/or touches the diaphragm wall depending on the overburden depth H and the embedded depth Z of an anchor, this study suggests the minimum overburden and embedded depths to avoid the yield of soils develop to ground surface and/or touch the diaphragm wall. When the embedded depth, overburden depth or fixed length of an anchor increases, the anchorage capacity also increases. Increasing fixed length should be the optimum method to increase the anchorage capacity for fixed length less than 20m. However, when the fixed length of an anchor exceeds 30 m, the increasing rate of anchorage capacity per fixed length decreases, and progressive yield occurs obviously between the fixed length and surrounding soil.

  2. Shear and Anchorage Behaviour of Fire Exposed Hollow Core Slabs

    NARCIS (Netherlands)

    Fellinger, J.H.H.


    Hollow core (HC) slabs are made of precast concrete with pretensioned strands. These slabs are popular as floor structures in offices and housing. At ambient conditions, the load bearing capacity can be dominated by four different failure modes, i.e. flexure, anchorage, shear compression and shear t

  3. Detection of bond failure in the anchorage zone of reinforced concrete beams via acoustic emission monitoring (United States)

    Abouhussien, Ahmed A.; Hassan, Assem A. A.


    In this study, acoustic emission (AE) monitoring was utilised to identify the onset of bond failure in reinforced concrete beams. Beam anchorage specimens were designed and tested to fail in bond in the anchorage zone. The specimens included four 250 × 250 × 1500 mm beams with four variable bonded lengths (100, 200, 300, and 400 mm). Meanwhile, an additional 250 × 250 × 2440 mm beam, with 200 mm bonded length, was tested to investigate the influence of sensor location on the identification of bond damage. All beams were tested under four-point loading setup and continuously monitored using three distributed AE sensors. These attached sensors were exploited to record AE signals resulting from both cracking and bond deterioration until failure. The variations in the number of AE hits and cumulative signal strength (CSS) versus test time were evaluated to achieve early detection of crack growth and bar slippage. In addition, AE intensity analysis was performed on signal strength of collected AE signals to develop two additional parameters: historic index (H (t)) and severity (S r). The analysis of these AE parameters enabled an early detection of both first cracks (at almost the mid-span of the beam) and bar slip in either of the anchorage zones at the beams’ end before their visual observation, regardless of sensor location. The results also demonstrated a clear correlation between the damage level in terms of crack development/measured free end bar slip and AE parameters (number of hits, CSS, H(t), and S r).

  4. Fast Deterministic Distributed Maximal Independent Set Computation on Growth-Bounded Graphs

    NARCIS (Netherlands)

    Kuhn, Fabian; Moscibroda, Thomas; Nieberg, Tim; Wattenhofer, Roger; Fraigniaud, Pierre


    The distributed complexity of computing a maximal independent set in a graph is of both practical and theoretical importance. While there exists an elegant O(log n) time randomized algorithm for general graphs, no deterministic polylogarithmic algorithm is known. In this paper, we study the problem

  5. ExbB Cytoplasmic Loop Deletions Cause Immediate, Proton Motive Force-Independent Growth Arrest (United States)

    Bulathsinghala, Charles M.; Jana, Bimal; Baker, Kristin R.


    The Escherichia coli TonB system consists of the cytoplasmic membrane proteins TonB, ExbB, and ExbD and multiple outer membrane active transporters for diverse iron siderophores and vitamin B12. The cytoplasmic membrane proteins harvest and transmit the proton motive force (PMF) to outer membrane transporters. This system, which spans the cell envelope, has only one component with a significant cytoplasmic presence, ExbB. Characterization of sequential 10-residue deletions in the ExbB cytoplasmic loop (residues 40 to 129; referred to as Δ10 proteins) revealed that it was required for all TonB-dependent activities, including interaction between the periplasmic domains of TonB and ExbD. Expression of eight out of nine of the Δ10 proteins at chromosomal levels led to immediate, but reversible, growth arrest. Arrest was not due to collapse of the PMF and did not require the presence of ExbD or TonB. All Δ10 proteins that caused growth arrest were dominant for that phenotype. However, several were not dominant for iron transport, indicating that growth arrest was an intrinsic property of the Δ10 variants, whether or not they could associate with wild-type ExbB proteins. The lack of dominance in iron transport also ruled out trivial explanations for growth arrest, such as high-level induction. Taken together, the data suggest that growth arrest reflected a changed interaction between the ExbB cytoplasmic loop and one or more unknown growth-regulatory proteins. Consistent with that, a large proportion of the ExbB cytoplasmic loop between transmembrane domain 1 (TMD1) and TMD2 is predicted to be disordered, suggesting the need for interaction with one or more cytoplasmic proteins to induce a final structure. PMID:23913327

  6. Acetylsalicylic acid interferes with embryonic kidney growth and development by a prostaglandin-independent mechanism (United States)

    Welham, Simon J M; Sparrow, Alexander J; Gardner, David S; Elmes, Matthew J


    AIM To evaluate the effects of the non-selective, non-steroidal anti-inflammatory drug (NSAID) acetylsalicylic acid (ASA), on ex vivo embryonic kidney growth and development. METHODS Pairs of fetal mouse kidneys at embryonic day 12.5 were cultured ex vivo in increasing concentrations of ASA (0.04-0.4 mg/mL) for up to 7 d. One organ from each pair was grown in control media and was used as the internal control for the experimental contralateral organ. In some experiments, organs were treated with ASA for 48 h and then transferred either to control media alone or control media containing 10 μmol/L prostaglandin E2 (PGE2) for a further 5 d. Fetal kidneys were additionally obtained from prostaglandin synthase 2 homozygous null or heterozygous (PTGS2-/- and PTGS2-/+) embryos and grown in culture. Kidney cross-sectional area was used to determine treatment effects on kidney growth. Whole-mount labelling to fluorescently detect laminin enabled crude determination of epithelial branching using confocal microscopy. RESULTS Increasing ASA concentration (0.1, 0.2 and 0.4 mg/mL) significantly inhibited metanephric growth (P < 0.05). After 7 d of culture, exposure to 0.2 mg/mL and 0.4 mg/mL reduced organ size to 53% and 23% of control organ size respectively (P < 0.01). Addition of 10 μmol/L PGE2 to culture media after exposure to 0.2 mg/mL ASA for 48 h resulted in a return of growth area to control levels. Application of control media alone after cessation of ASA exposure showed no benefit on kidney growth. Despite the apparent recovery of growth area with 10 μmol/L PGE2, no obvious renal tubular structures were formed. The number of epithelial tips generated after 48 h exposure to ASA was reduced by 40% (0.2 mg/mL; P < 0.05) and 47% (0.4 mg/mL; P < 0.01). Finally, growth of PTGS2-/- and PTGS2+/- kidneys in organ culture showed no differences, indicating that PTGS2 derived PGE2 may at best have a minor role. CONCLUSION ASA reduces early renal growth and development but the

  7. Uvulo-glossopharyngeal dimensions in non-extraction, extraction with minimum anchorage, and extraction with maximum anchorage. (United States)

    Germec-Cakan, Derya; Taner, Tulin; Akan, Seden


    The aim of this study was to investigate upper respiratory airway dimensions in non-extraction and extraction subjects treated with minimum or maximum anchorage. Lateral cephalograms of 39 Class I subjects were divided into three groups (each containing 11 females and 2 males) according to treatment procedure: group 1, 13 patients treated with extraction of four premolars and minimum anchorage; group 2, 13 cases treated non-extraction with air-rotor stripping (ARS); and group 3, 13 bimaxillary protrusion subjects treated with extraction of four premolars and maximum anchorage. The mean ages of the patients were 18.1 ± 3.7, 17.8 ± 2.4, and 15.5 ± 0.88 years, respectively. Tongue, soft palate, hyoid position, and upper airway measurements were made on pre- and post-treatment lateral cephalograms and the differences between the mean measurements were tested using Wilcoxon signed-ranks test. Superior and middle airway space increased significantly (P extraction treatment using maximum anchorage has a reducing effect on the middle and inferior airway dimensions.

  8. Role of manganese superoxide dismutase on growth and invasive properties of human estrogen-independent breast cancer cells. (United States)

    Kattan, Zilal; Minig, Vanessa; Leroy, Pierre; Dauça, Michel; Becuwe, Philippe


    Manganese superoxide dismutase (MnSOD) is known to play a role in cancer. MnSOD exerts a tumor suppressive effect in estrogen-dependent human breast cancer cells. In the present study we investigated the in vitro role of MnSOD in the growth of some aggressive and highly metastatic estrogen-independent breast cancer cells, i.e., MDA-MB231 and SKBR3 cells. We show that estrogen-independent cells expressed a significantly higher basal MnSOD level compared to estrogen-dependent human breast cancer cell lines (MCF-7 and T47D). For MDA-MB231 cells, the high-MnSOD level was accompanied by an overproduction of intracellular hydrogen peroxide (H2O2) and by a low expression of the major H2O2-detoxifying enzymes, catalase, and peroxiredoxin 3, compared to MCF-7 cells. Suppression of MnSOD expression by antisense RNA was associated with a decrease of H2O2 content and caused a stimulation of growth with a reduced cell doubling time but induced a decrease of colony formation. Furthermore, treatment of MDA-MB231 cells with H2O2 scavengers markedly reduced tumor cell growth and colony formation. In addition, MnSOD suppression or treatment with H2O2 scavengers reduced the invasive properties of MDA-MB231 cells up to 43%, with a concomitant decrease of metalloproteinase-9 activity. We conclude that MnSOD plays a role in regulating tumor cell growth and invasive properties of estrogen-independent metastatic breast cancer cells. These action are mediated by MnSOD-dependent H2O2 production. In addition, these results suggest that MnSOD up-regulation may be one mechanism that contributes to the development of metastatic breast cancers.

  9. Posttraumatic Growth and Depreciation as Independent Experiences and Predictors of Well-Being (United States)

    Cann, Arnie; Calhoun, Lawrence G.; Tedeschi, Richard G.; Solomon, David T.


    Positive changes (posttraumatic growth [PTG]) and negative changes (posttraumatic depreciation [PTD]) were assessed using the PTGI-42 with persons reporting changes from a stressful event. PTG and PTD were uncorrelated, and PTG was much greater than PTD. PTG was positively related to disruption of core beliefs and recent deliberate rumination and…

  10. Insulin-like growth factor-binding protein-2 promotes prostate cancer cell growth via IGF-dependent or -independent mechanisms and reduces the efficacy of docetaxel (United States)

    Uzoh, C C; Holly, J M P; Biernacka, K M; Persad, R A; Bahl, A; Gillatt, D; Perks, C M


    Background: The development of androgen independence, chemo-, and radioresistance are critical markers of prostate cancer progression and the predominant reasons for its high mortality. Understanding the resistance to therapy could aid the development of more effective treatments. Aim: The aim of this study is to investigate the effects of insulin-like growth factor-binding protein-2 (IGFBP-2) on prostate cancer cell proliferation and its effects on the response to docetaxel. Methods: DU145 and PC3 cells were treated with IGFBP-2, insulin-like growth factor I (IGF-I) alone or in combination with blockade of the IGF-I receptor or integrin receptors. Cells were also treated with IGFBP-2 short interfering ribonucleic acid with or without a PTEN (phosphatase and tensin homologue deleted on chromosome 10) inhibitor or docetaxel. Tritiated thymidine incorporation was used to measure cell proliferation and Trypan blue cell counting for cell death. Levels of IGFBP-2 mRNA were measured using RT–PCR. Abundance and phosphorylation of proteins were assessed using western immunoblotting. Results: The IGFBP-2 promoted cell growth in both cell lines but with PC3 cells this was in an IGF-dependent manner, whereas with DU145 cells the effect was independent of IGF receptor activation. This IGF-independent effect of IGFBP-2 was mediated by interaction with β-1-containing integrins and a consequent increase in PTEN phosphorylation. We also determined that silencing IGFBP-2 in both cell lines increased the sensitivity of the cells to docetaxel. Conclusion: The IGFBP-2 has a key role in the growth of prostate cancer cells, and silencing IGFBP-2 expression reduced the resistance of these cells to docetaxel. Targeting IGFBP-2 may increase the efficacy of docetaxel. PMID:21487405

  11. A RAS oncogene imparts growth factor independence to myeloid cells that abnormally regulate protein kinase C: a nonautocrine transformation pathway. (United States)

    Boswell, H S; Nahreini, T S; Burgess, G S; Srivastava, A; Gabig, T G; Inhorn, L; Srour, E F; Harrington, M A


    The factor-dependent cell line FDC-P1 has been utilized as a model of interleukin 3 (IL-3)-dependent myeloid cell proliferation. However, it has been recently observed that active phorbol esters (e.g., phorbol 12-myristate 13-acetate) may entirely replace IL-3 to promote its proliferation. These observations reveal abnormal regulation of protein kinase C (pkC) (absence of downregulation or overexpression). This property allowed a test of the hypothesis that the T24 RAS (codon 12) oncogene acts by constitutive and persistent pkC activation, driving proliferation. FDC-P1 cells were transfected by electroporation with the T24 RAS-containing vector pAL 8, or with a control vector pSVX Zip Neo, and neomycin-resistant clones were selected. Multiple RAS-transfectant clones were categorized for their growth factor requirement and incorporation of the 6.6-kb human mutant H-RAS genome. IL-3-independent clones had incorporated multiple (more than two) copies of the entire 6.6-kb RAS genome. The incorporation of multiple 6.6-kb RAS genomes was correlated with high-level p21 RAS expression. No evidence for autostimulatory growth factor production by clones containing the RAS oncogene was observed. Thus, acquisition of growth factor independence in myeloid cells by abundant expression of a RAS oncogene is linked, in part, to abnormal regulation of pkC, which acts as a collaborating oncogene.

  12. Growth hormone mediates pubertal skeletal development independent of hepatic IGF-1 production. (United States)

    Courtland, Hayden-William; Sun, Hui; Beth-On, Mordechay; Wu, Yingjie; Elis, Sebastien; Rosen, Clifford J; Yakar, Shoshana


    Deficiencies in either growth hormone (GH) or insulin-like growth factor 1 (IGF-1) are associated with reductions in bone size during growth in humans and animal models. Liver-specific IGF-1-deficient (LID) mice, which have 75% reductions in serum IGF-1, were created previously to separate the effects of endocrine (serum) IGF-1 from autocrine/paracrine IGF-1. However, LID mice also have two- to threefold increases in GH, and this may contribute to the observed pubertal skeletal phenotype. To clarify the role of GH in skeletal development under conditions of significantly reduced serum IGF-1 levels (but normal tissue IGF-1 levels), we studied the skeletal response of male LID and control mice to GH inhibition by pegvisomant from 4 to 8 weeks of age. Treatment of LID mice with pegvisomant resulted in significant reductions in body weight, femur length (Le), and femur total area (Tt.Ar), as well as further reductions in serum IGF-1 levels by 8 weeks of age, compared with the mean values of vehicle-treated LID mice. Reductions in both Tt.Ar and Le were proportional after treatment with pegvisomant. On the other hand, the relative amount of cortical tissue formed (RCA) in LID mice treated with pegvisomant was significantly less than that in both vehicle-treated LID and control mice, indicating that antagonizing GH action, either directly (through GH receptor signaling inhibition) or indirectly (through further reductions in serum/tissue IGF-1 levels), results in disproportionate reductions in the amount of cortical bone formed. This resulted in bones with significantly reduced mechanical properties (femoral whole-bone stiffness and work to failure were markedly decreased), suggesting that compensatory increases of GH in states of IGF-1 deficiency (LID mice) act to protect against a severe inhibition of bone modeling during growth, which otherwise would result in bones that are too weak for normal and/or extreme loading conditions.

  13. Inhibition of autophagy attenuates pancreatic cancer growth independent of TP53/TRP53 status. (United States)

    Yang, Annan; Kimmelman, Alec C


    Basal levels of autophagy are elevated in most pancreatic ductal adenocarcinomas (PDAC). Suppressing autophagy pharmacologically using chloroquine (CQ) or genetically with RNAi to essential autophagy genes inhibits human pancreatic cancer growth in vitro and in vivo, which presents possible treatment opportunities for PDAC patients using the CQ-derivative hydroxychloroquine (HCQ). Indeed, such clinical trials are ongoing. However, autophagy is a complex cellular mechanism to maintain cell homeostasis under stress. Based on its biological role, a dual role of autophagy in tumorigenesis has been proposed: at tumor initiation, autophagy helps maintain genomic stability and prevent tumor initiation; while in advanced disease, autophagy degrades and recycles cellular components to meet the metabolic needs for rapid growth. This model was proven to be the case in mouse lung tumor models. However, in contrast to prior work in various PDAC model systems, loss of autophagy in PDAC mouse models with embryonic homozygous Trp53 deletion does not inhibit tumor growth and paradoxically increases progression. This raised concerns whether there may be a genotype-dependent reliance of PDAC on autophagy. In a recent study, our group used a Trp53 heterozygous mouse PDAC model and human PDX xenografts to address the question. Our results demonstrate that autophagy inhibition was effective against PDAC tumors irrespective of TP53/TRP53 status.

  14. Predicting the dynamics of a native Araucaria forest using a distance-independent individual tree-growth model

    Directory of Open Access Journals (Sweden)

    Enrique Orellana


    Full Text Available Background: In recent decades, native Araucaria forests in Brazil have become fragmented due to the conversion of forest to agricultural lands and commercial tree plantations. Consequently, the forest dynamics in this forest type have been poorly investigated, as most fragments are poorly structured in terms of tree size and diversity. Methods: We developed a distance-independent individual tree-growth model to simulate the forest dynamics in a native Araucaria forest located predominantly in southern Brazil. The data were derived from 25 contiguous plots (1 ha established in a protected area left undisturbed for the past 70 years. The plots were measured at 3-year intervals from their establishment in 2002. All trees above a 10-cm diameter at breast height were tagged, identified as to species, and measured. Because this forest type comprises hundreds of tree species, we clustered them into six ecological groups: understory, subcanopy, upper canopy shade-tolerant, upper canopy light-demanding, pioneer, and emergent. The diameter increment, survival, and recruitment sub-models were fitted for each species group, and parameters were implemented in a simulation software to project the forest dynamics. The growth model was validated using independent data collected from another research area of the same forest type. To simulate the forest dynamics, we projected the species group and stand basal areas for 50 years under three different stand-density conditions: low, average, and high. Results: Emergent species tended to grow in basal area, irrespective of the forest density conditions. Conversely, shade-tolerant species tended to decline over the years. Under low-density conditions, the model showed a growth tendency for the stand basal area, while under average-density conditions, forest growth tended to stabilize within 30 years. Under high-density conditions, the model indicated a decline in the stand basal area from the onset of the simulation

  15. Troglitazone inhibits cell proliferation by attenuation of epidermal growth factor receptor signaling independent of peroxisome proliferator-activated receptor γ

    Institute of Scientific and Technical Information of China (English)

    Xiaoqi Li; Xuanming Yang; Youli Xu; Xuejun Jiang; Xin Li; Fajun Nan; Hong Tang


    Peroxisome proliferator-activated receptors (PPAR) belong to the nuclear hormone receptor superfamily of ligand-dependent transcription factors. Recent results have shown that agonists of PPARy, such as troglitazone (TGZ), can inhibit cell proliferation and promote cell differentiation independent of PPARγ. In the present study, we provide evidence that TGZ may bind directly to EGFR and trigger its signaling and internalization independent of PPARγ. Detailed studies revealed that prolonged incubation with TGZ effectively attenuated EGFR signaling by target-ing the receptor to the endo-lysosomal degradation machinery. Although the extracellular signal-regulated kinase-signaling pathway was transiently activated by TGZ in EGFR overexpressing cancer cells, inhibition of EGF-induced Akt phosphorylation most likely accounted for the growth arrest of tumor cells caused by TGZ at pharmacologically achievable concentrations. Therefore, we have provided a new line of evidence indicating that TGZ inhibits cell pro-liferation by promoting EGFR degradation and attenuating Akt phosphorylation.

  16. The emissions, energy consumption, and growth nexus. Evidence from the commonwealth of independent states

    Energy Technology Data Exchange (ETDEWEB)

    Apergis, Nicholas [Department of Banking and Financial Management, University of Piraeus, Karaoli and Dimitriou 80, Piraeus, ATTIKI 18534 (Greece); Payne, James E. [Interim Dean, College of Arts and Sciences, Illinois State University, Normal, IL 61790-4100 (United States)


    This study examines the causal relationship between carbon dioxide emissions, energy consumption, and real output within a panel vector error correction model for eleven countries of the Commonwealth of Independent States over the period 1992-2004. In the long-run, energy consumption has a positive and statistically significant impact on carbon dioxide emissions while real output follows an inverted U-shape pattern associated with the Environmental Kuznets Curve (EKC) hypothesis. The short-run dynamics indicate unidirectional causality from energy consumption and real output, respectively, to carbon dioxide emissions along with bidirectional causality between energy consumption and real output. In the long-run there appears to be bidirectional causality between energy consumption and carbon dioxide emissions. (author)

  17. The emissions, energy consumption, and growth nexus: Evidence from the commonwealth of independent states

    Energy Technology Data Exchange (ETDEWEB)

    Apergis, Nicholas, E-mail: napergis@unipi.g [Department of Banking and Financial Management, University of Piraeus, Karaoli and Dimitriou 80, Piraeus, ATTIKI 18534 (Greece); Payne, James E., E-mail: jepayne@ilstu.ed [College of Arts and Sciences, Illinois State University, Normal, IL 61790-4100 (United States)


    This study examines the causal relationship between carbon dioxide emissions, energy consumption, and real output within a panel vector error correction model for eleven countries of the Commonwealth of Independent States over the period 1992-2004. In the long-run, energy consumption has a positive and statistically significant impact on carbon dioxide emissions while real output follows an inverted U-shape pattern associated with the Environmental Kuznets Curve (EKC) hypothesis. The short-run dynamics indicate unidirectional causality from energy consumption and real output, respectively, to carbon dioxide emissions along with bidirectional causality between energy consumption and real output. In the long-run there appears to be bidirectional causality between energy consumption and carbon dioxide emissions.

  18. Both canonical and non-canonical Wnt signaling independently promote stem cell growth in mammospheres.

    Directory of Open Access Journals (Sweden)

    Alexander M Many

    Full Text Available The characterization of mammary stem cells, and signals that regulate their behavior, is of central importance in understanding developmental changes in the mammary gland and possibly for targeting stem-like cells in breast cancer. The canonical Wnt/β-catenin pathway is a signaling mechanism associated with maintenance of self-renewing stem cells in many tissues, including mammary epithelium, and can be oncogenic when deregulated. Wnt1 and Wnt3a are examples of ligands that activate the canonical pathway. Other Wnt ligands, such as Wnt5a, typically signal via non-canonical, β-catenin-independent, pathways that in some cases can antagonize canonical signaling. Since the role of non-canonical Wnt signaling in stem cell regulation is not well characterized, we set out to investigate this using mammosphere formation assays that reflect and quantify stem cell properties. Ex vivo mammosphere cultures were established from both wild-type and Wnt1 transgenic mice and were analyzed in response to manipulation of both canonical and non-canonical Wnt signaling. An increased level of mammosphere formation was observed in cultures derived from MMTV-Wnt1 versus wild-type animals, and this was blocked by treatment with Dkk1, a selective inhibitor of canonical Wnt signaling. Consistent with this, we found that a single dose of recombinant Wnt3a was sufficient to increase mammosphere formation in wild-type cultures. Surprisingly, we found that Wnt5a also increased mammosphere formation in these assays. We confirmed that this was not caused by an increase in canonical Wnt/β-catenin signaling but was instead mediated by non-canonical Wnt signals requiring the receptor tyrosine kinase Ror2 and activity of the Jun N-terminal kinase, JNK. We conclude that both canonical and non-canonical Wnt signals have positive effects promoting stem cell activity in mammosphere assays and that they do so via independent signaling mechanisms.

  19. Growth Inhibition Occurs Independently of Cell Mortality in Tomato (Solanum lycopersicum) Exposed to High Cadmium Concentrations

    Institute of Scientific and Technical Information of China (English)

    Christine Delpérée; Stanley Lutts


    In order to analyze the adaptation potential of tomato shoots to a sudden increase in Cd concentration, tomato plants (Solanum lycopersicum L. var. Ailsa Craig) were exposed under controlled environmental conditions to a high dose of this heavy metal (250 μM CdCl2>) in nutrient solution for 7 and 14 d. Both root and shoot growth was completely inhibited but all plants remained alive until the end of the treatment. Cell viability remained unaffected but the activity of the mitochondrial alternative pathway was stimulated by Cd stress at the expense of the cytochrome pathway. Cadmium concentration was higher in roots than in shoots and a decrease In the rate of net Cd translocation was noticed during the second week of stress. Cadmium decreased both leaf conductance (g1>) and chlorophyll concentration. However, the effect on net CO2 assimilation remained limited and soluble sugars accumulated in leaves. Photochemical efficiency of PSll (FvlFm) was not affected despite a decrease in the number of reaction centers and an inhibition of electron transfer to acceptors of PSII. It is concluded that tomato shoot may sustain short term exposure to high doses of cadmium despite growth inhibition. This property implies several physiological strategies linked to both avoidance and tolerance mechanisms.

  20. Synergetic material and structure optimization yields robust spider web anchorages. (United States)

    Pugno, Nicola M; Cranford, Steven W; Buehler, Markus J


    Millions of years of evolution have adapted spider webs to achieve a range of properties, including the well-known capture of prey, with efficient use of materials. One feature that remains poorly understood is the attachment disc, a network of silk fibers that mechanically anchors a web to its environment. Experimental observations suggest that one possible attachment disc adheres to a substrate through multiple symmetrically branched structures composed of sub-micrometer scale silk fibers. Here, a theoretical model is used to explore the adaptation of the strength of attachment of such an anchorage, and complementary mesoscale simulations are applied to demonstrate a novel mechanism of synergetic material and structural optimization, such that the maximum anchorage strength can be achieved regardless of the initial anchor placement or material type. The optimal delamination (peeling) angle is facilitated by the inherent extensibility of silk, and is attained automatically during the process of delamination. This concept of self-optimizing peeling angle suggests that attachment discs do not require precise placement by the spider, irrespective of adhesion strength. Additional hierarchical branching of the anchorage increases efficiency, where both the delamination force and toughness modulus increase with a splitting of the cross-sectional area.

  1. Image guided placement of temporary anchorage devices for tooth movement

    Energy Technology Data Exchange (ETDEWEB)

    Bahl-Palomo, L.; Bissada, N. [Case Western Reserve Univ. School of Dental Medicine, Dept. of Periodontics, Cleveland, OH (United States); Palomo, J.M.; Hans, M.G. [Case Western Reserve Univ. School of Dental Medicine, Dept. of Orthodontics, Cleveland, OH (United States)


    The aim of this project is to develop an image guided protocol for placement of a temporary anchorage device without surgically reflecting a mucoperiosteal flap. Eighteen orthodontic cases were selected for skeletal anchorage from the department of orthodontics at Case University. CBCT images of the subjects were taken using the Hitachi CB MercuRay system set at 15 mA, 120 kVp. CBCT images evaluated the ideal location for TAD placement in three dimensions. Horizontal and vertical linear measurements were taken from fixed dental landmarks to clearly define the location for placement. Transverse slices were used to evaluate the thickness of the buccal plate. Using the transverse view, the angle of insertion was determined such that the maximum buccal plate surface area would contact the screw. TADs were placed in the optimum location, with the most appropriate angle of insertion using a closed approach and with minimal local anesthesia and without flap elevation. Results: All TADs were placed without anatomic encroachment and enabled fixed orthodontic anchorage. (orig.)

  2. Mos in the Oocyte: How to Use MAPK Independently of Growth Factors and Transcription to Control Meiotic Divisions

    Directory of Open Access Journals (Sweden)

    Aude Dupré


    Full Text Available In many cell types, the mitogen-activated protein kinase (MAPK also named extracellular signal-regulated kinase (ERK is activated in response to a variety of extracellular growth factor-receptor interactions and leads to the transcriptional activation of immediate early genes, hereby influencing a number of tissue-specific biological activities, as cell proliferation, survival and differentiation. In one specific cell type however, the female germ cell, MAPK does not follow this canonical scheme. In oocytes, MAPK is activated independently of growth factors and tyrosine kinase receptors, acts independently of transcriptional regulation, plays a crucial role in controlling meiotic divisions, and is under the control of a peculiar upstream regulator, the kinase Mos. Mos was originally identified as the transforming gene of Moloney murine sarcoma virus and its cellular homologue was the first proto-oncogene to be molecularly cloned. What could be the specific roles of Mos that render it necessary for meiosis? Which unique functions could explain the evolutionary cost to have selected one gene to only serve for few hours in one very specific cell type? This review discusses the original features of MAPK activation by Mos and the roles of this module in oocytes.

  3. [Influence of Smad4-independent pathway of transforming growth factor beta1 on the biological activity of pancreatic cancer cells]. (United States)

    Chen, Ying; Zhu, Ming-hua; Yu, Guan-zhen; Li, Fang-mei; Liu, Xiao-hong


    To study effects of the expression of transforming growth factor (TGF)-beta1 on the growth of Smad4-null pancreatic cancer cells. TGF-beta1 eukaryotic expression vector was transfected into pancreatic cancer cell line BxPC3. Effects of the expressison of TGF-beta1 was studied by growth curve analysis and flow cytometry. Cell motility was monitored by wound-healing assay. Western blot was used to estimate the expression level of p21(WAF/CLIP1), a cyclin-dependent kinase inhibitor. Transfection of TGF-beta1 changed the morphology of BxPC3 into spindle shaped cells. The growth rate of BxPC3 began to decrease after the fourth day of TGF-beta1 transfection, compared with the control groups. Flow cytometry showed that the percentages of cells in the S phase were (27.53 +/- 0.02)%, (26.32 +/- 0.01)% and (17.01 +/- 0.03)% in naïve BxPC3, vector-control group and TGF-beta1 transfection group respectively. Lesser cells entered the S phase after TGF-beta1 transfection (P BxPC3 and vector groups (P > 0.05). The expression of p21(WAF/CLIP1) increased upon the expression of TGF-beta1. The Smad4-independent pathway of TGF-beta1 not only induces epithelial-mesenchymal transition in pancreatic cancer BxPC3, but also inhibits its growth through the up-regulation of p21(WAF/CLIP1).

  4. High temperatures limit plant growth but hasten flowering in root chicory (Cichorium intybus) independently of vernalisation. (United States)

    Mathieu, Anne-Sophie; Lutts, Stanley; Vandoorne, Bertrand; Descamps, Christophe; Périlleux, Claire; Dielen, Vincent; Van Herck, Jean-Claude; Quinet, Muriel


    An increase in mean and extreme summer temperatures is expected as a consequence of climate changes and this might have an impact on plant development in numerous species. Root chicory (Cichorium intybus L.) is a major crop in northern Europe, and it is cultivated as a source of inulin. This polysaccharide is stored in the tap root during the first growing season when the plant grows as a leafy rosette, whereas bolting and flowering occur in the second year after winter vernalisation. The impact of heat stress on plant phenology, water status, photosynthesis-related parameters, and inulin content was studied in the field and under controlled phytotron conditions. In the field, plants of the Crescendo cultivar were cultivated under a closed plastic-panelled greenhouse to investigate heat-stress conditions, while the control plants were shielded with a similar, but open, structure. In the phytotrons, the Crescendo and Fredonia cultivars were exposed to high temperatures (35°C day/28°C night) and compared to control conditions (17°C) over 10 weeks. In the field, heat reduced the root weight, the inulin content of the root and its degree of polymerisation in non-bolting plants. Flowering was observed in 12% of the heat stressed plants during the first growing season in the field. In the phytotron, the heat stress increased the total number of leaves per plant, but reduced the mean leaf area. Photosynthesis efficiency was increased in these plants, whereas osmotic potential was decreased. High temperature was also found to induced flowering of up to 50% of these plants, especially for the Fredonia cultivar. In conclusion, high temperatures induced a reduction in the growth of root chicory, although photosynthesis is not affected. Flowering was also induced, which indicates that high temperatures can partly substitute for the vernalisation requirement for the flowering of root chicory.

  5. p19Arf suppresses growth, progression, and metastasis of Hras-driven carcinomas through p53-dependent and -independent pathways.

    Directory of Open Access Journals (Sweden)

    Karen S Kelly-Spratt


    Full Text Available Ectopic expression of oncogenes such as Ras induces expression of p19(Arf, which, in turn, activates p53 and growth arrest. Here, we used a multistage model of squamous cell carcinoma development to investigate the functional interactions between Ras, p19(Arf, and p53 during tumor progression in the mouse. Skin tumors were induced in wild-type, p19(Arf-deficient, and p53-deficient mice using the DMBA/TPA two-step protocol. Activating mutations in Hras were detected in all papillomas and carcinomas examined, regardless of genotype. Relative to wild-type mice, the growth rate of papillomas was greater in p19(Arf-deficient mice, and reduced in p53-deficient mice. Malignant conversion of papillomas to squamous cell carcinomas, as well as metastasis to lymph nodes and lungs, was markedly accelerated in both p19 (Arf- and p53-deficient mice. Thus, p19(Arf inhibits the growth rate of tumors in a p53-independent manner. Through its regulation of p53, p19(Arf also suppresses malignant conversion and metastasis. p53 expression was upregulated in papillomas from wild-type but not p19( Arf-null mice, and p53 mutations were more frequently seen in wild-type than in p19( Arf-null carcinomas. This indicates that selection for p53 mutations is a direct result of signaling from the initiating oncogenic lesion, Hras, acting through p19(Arf.

  6. Neurotensin-induced Erk1/2 phosphorylation and growth of human colonic cancer cells are independent from growth factors receptors activation

    Energy Technology Data Exchange (ETDEWEB)

    Massa, Fabienne; Tormo, Aurelie; Beraud-Dufour, Sophie; Coppola, Thierry [Institut de Pharmacologie Moleculaire et Cellulaire, Universite de Nice-Sophia Antipolis, CNRS UMR 6097, 660 route des Lucioles, 06560 Valbonne (France); Mazella, Jean, E-mail: [Institut de Pharmacologie Moleculaire et Cellulaire, Universite de Nice-Sophia Antipolis, CNRS UMR 6097, 660 route des Lucioles, 06560 Valbonne (France)


    Highlights: {yields} We compare intracellular pathways of NT and EGF in HT29 cells. {yields} NT does not transactivate EGFR. {yields} Transactivation of EGFR is not a general rule in cancer cell growth. -- Abstract: Neurotensin (NT) promotes the proliferation of human colonic cancer cells by undefined mechanisms. We already demonstrated that, in the human colon adenocarcinoma cell line HT29, the effects of NT were mediated by a complex formed between the NT receptor-1 (NTSR1) and-3 (NTSR3). Here we examined cellular mechanisms that led to NT-induced MAP kinase phosphorylation and growth factors receptors transactivation in colonic cancer cells and proliferation in HT29 cells. With the aim to identify upstream signaling involved in NT-elicited MAP kinase activation, we found that the stimulatory effects of the peptide were totally independent from the activation of the epidermal growth factor receptor (EGFR) both in the HT29 and the HCT116 cells. NT was unable to promote phosphorylation of EGFR and to compete with EGF for its binding to the receptor. Pharmacological approaches allowed us to differentiate EGF and NT signaling in HT29 cells since only NT activation of Erk1/2 was shown to be sensitive to PKC inhibitors and since only NT increased the intracellular level of calcium. We also observed that NT was not able to transactivate Insulin-like growth factor receptor. Our findings indicate that, in the HT29 and HCT116 cell lines, NT stimulates MAP kinase phosphorylation and cell growth by a pathway which does not involve EGF system but rather NT receptors which transduce their own intracellular effectors. These results indicate that depending on the cell line used, blocking EGFR is not the general rule to inhibit NT-induced cancer cell proliferation.

  7. External post-tensioning of cfrp tendons using integrated sleeve-wedge anchorage

    DEFF Research Database (Denmark)

    Schmidt, Jacob Wittrup; Bennitz, Anders; Goltermann, Per


    Strengthening of structures using external post-tension CFRP systems have proven to be anefficient method as such system increases the structural capacity and reduces cracks and deflection. Sufficient anchorage is of significant importance since the anchorage provides the connection between...... the post-tensioning system and the remaining structure. A special designed integrated sleeve-wedge anchorage has therefore been designed to improve the reliability of the mounting procedure, reduce the possible modes of failure and thus provide desired anchorage. The present research shows that adequate...

  8. Optimal design of metabolic flux analysis experiments for anchorage-dependent mammalian cells using a cellular automaton model. (United States)

    Meadows, Adam L; Roy, Siddhartha; Clark, Douglas S; Blanch, Harvey W


    Metabolic flux analysis (MFA) is widely used to quantify metabolic pathway activity. Typical applications involve isotopically labeled substrates, which require both metabolic and isotopic steady states for simplified data analysis. For bacterial systems, these steady states are readily achieved in chemostat cultures. However, mammalian cells are often anchorage dependent and experiments are typically conducted in batch or fed-batch systems, such as tissue culture dishes or microcarrier-containing bioreactors. Surface adherence may cause deviations from exponential growth, resulting in metabolically heterogeneous populations and a varying number of cellular "nearest neighbors" that may affect the observed metabolism. Here, we discuss different growth models suitable for deconvoluting these effects and their application to the design and optimization of MFA experiments employing surface-adherent mammalian cells. We describe a stochastic two-dimensional (2D) cellular automaton model, with empirical descriptions of cell number and non-growing cell fraction, suitable for easy application to most anchorage-dependent mammalian cell cultures. Model utility was verified by studying the impact of contact inhibition on the growth rate, specific extracellular flux rates, and isotopic labeling in lactate for MCF7 cells, a commonly studied breast cancer cell line. The model successfully defined the time over which exponential growth and a metabolically homogeneous growing cell population could be assumed. The cellular automaton model developed is shown to be a useful tool in designing optimal MFA experiments.

  9. Growth Factor Independence-1 (Gfi1) Is Required for Pancreatic Acinar Unit Formation and Centroacinar Cell Differentiation

    DEFF Research Database (Denmark)

    Qu, Xiaoling; Nyeng, Pia; Xiao, Fan


    BACKGROUND & AIMS: The genetic specification of the compartmentalized pancreatic acinar/centroacinar unit is poorly understood. Growth factor independence-1 (Gfi1) is a zinc finger transcriptional repressor that regulates hematopoietic stem cell maintenance, pre-T-cell differentiation, formation...... of pancreatic acinar cells as well as the centroacinar cells (CACs) in Gfi1(-/-) mice when compared with wild-type littermates. Pancreatic endocrine differentiation, islet architecture, and function were unaffected. Organ domain patterning and the formation of ductal cells occurred normally during the murine...... of granulocytes, inner ear hair cells, and the development of secretory cell types in the intestine. As GFI1/Gfi1 is expressed in human and rodent pancreas, we characterized the potential function of Gfi1 in mouse pancreatic development. METHODS: Gfi1 knockout mice were analyzed at histological and molecular...

  10. Up-regulation of Bcl-2 is required for the progression of prostate cancer cells from an androgen-dependent to an androgen-independent growth stage

    Institute of Scientific and Technical Information of China (English)

    Yuting Lin; Junichi Fukuchi; Richard A Hiipakka; John M Kokontis; Jialing Xiang


    Bcl-2 is an anti-apoptotic oncoprotein and its protein levels are inversely correlated with prognosis in many cancers.However, the role of Bcl-2 in the progression of prostate cancer is not clear. Here we report that Bcl-2 is required for the progression of LNCaP prostate cancer cells from an androgen-dependent to an androgen-independent growth stage. The mRNA and protein levels of Bcl-2 are significantly increased in androgen-independent prostate cancer cells, shRNA-mediated gene silencing of Bcl-2 in androgen-independent prostate cancer cells promotes UV-induced apoptosis and suppresses the growth of prostate tumors in vivo. Growing androgen-dependent cells under androgen-deprivation conditions results in formation of androgen-independent colonies; and the transition from androgen-dependent to androgen-independent growth is blocked by ectopic expression of the Bcl-2 antagonist Bax or Bcl-2 shRNA. Thus, our results demonstrate that Bcl-2 is not only critical for the survival of androgen-independent prostate cancer cells, but is also required for the progression of prostate cancer cells from an androgen-dependent to an androgen-independent growth stage.

  11. Downregulation of autophagy by Bcl-2 promotes MCF7 breast cancer cell growth independent of its inhibition of apoptosis. (United States)

    Oh, S; Xiaofei, E; Ni, D; Pirooz, S D; Lee, J-Y; Lee, D; Zhao, Z; Lee, S; Lee, H; Ku, B; Kowalik, T; Martin, S E; Oh, B-H; Jung, J U; Liang, C


    The anti-apoptotic Bcl-2 protein, which confers oncogenic transformation and drug resistance in most human cancers, including breast cancer, has recently been shown to effectively counteract autophagy by directly targeting Beclin1, an essential autophagy mediator and tumor suppressor. However, it remains unknown whether autophagy inhibition contributes to Bcl-2-mediated oncogenesis. Here, by using a loss-of-function mutagenesis study, we show that Bcl-2-mediated antagonism of autophagy has a critical role in enhancing the tumorigenic properties of MCF7 breast cancer cells independent of its anti-apoptosis activity. A Bcl-2 mutant defective in apoptosis inhibition but competent for autophagy suppression promotes MCF7 breast cancer cell growth in vitro and in vivo as efficiently as wild-type Bcl-2. The growth-promoting activity of this Bcl-2 mutant is strongly correlated with its suppression of Beclin1-dependent autophagy, leading to sustained p62 expression and increased DNA damage in xenograft tumors, which may directly contribute to tumorigenesis. Thus, the anti-autophagic property of Bcl-2 is a key feature of Bcl-2-mediated oncogenesis and may in some contexts, serve as an attractive target for breast and other cancer therapies.

  12. Growth rate of late passage sarcoma cells is independent of epigenetic events but dependent on the amount of chromosomal aberrations

    Energy Technology Data Exchange (ETDEWEB)

    Becerikli, Mustafa; Jacobsen, Frank; Rittig, Andrea; Köhne, Wiebke [Department of Plastic Surgery, BG University Hospital Bergmannsheil, Ruhr-University Bochum (Germany); Nambiar, Sandeep; Mirmohammadsadegh, Alireza; Stricker, Ingo; Tannapfel, Andrea [Institute of Pathology, Ruhr-University Bochum (Germany); Wieczorek, Stefan; Epplen, Joerg Thomas [Department of Human Genetics, Ruhr-University Bochum (Germany); Tilkorn, Daniel [Department of Plastic Surgery, BG University Hospital Bergmannsheil, Ruhr-University Bochum (Germany); Steinstraesser, Lars, E-mail: [Department of Plastic Surgery, BG University Hospital Bergmannsheil, Ruhr-University Bochum (Germany)


    Soft tissue sarcomas (STS) are characterized by co-participation of several epigenetic and genetic events during tumorigenesis. Having bypassed cellular senescence barriers during oncogenic transformation, the factors further affecting growth rate of STS cells remain poorly understood. Therefore, we investigated the role of gene silencing (DNA promoter methylation of LINE-1, PTEN), genetic aberrations (karyotype, KRAS and BRAF mutations) as well as their contribution to the proliferation rate and migratory potential that underlies “initial” and “final” passage sarcoma cells. Three different cell lines were used, SW982 (synovial sarcoma), U2197 (malignant fibrous histiocytoma (MFH)) and HT1080 (fibrosarcoma). Increased proliferative potential of final passage STS cells was not associated with significant differences in methylation (LINE-1, PTEN) and mutation status (KRAS, BRAF), but it was dependent on the amount of chromosomal aberrations. Collectively, our data demonstrate that these fairly differentiated/advanced cancer cell lines have still the potential to gain an additional spontaneous growth benefit without external influences and that maintenance of increased proliferative potential towards longevity of STS cells (having crossed senescence barriers) may be independent of overt epigenetic alterations. -- Highlights: Increased proliferative potential of late passage STS cells was: • Not associated with epigenetic changes (methylation changes at LINE-1, PTEN). • Not associated with mutation status of KRAS, BRAF. • Dependent on presence/absence of chromosomal aberrations.

  13. Growth of Verticillium longisporum in Xylem Sap of Brassica napus is Independent from Cultivar Resistance but Promoted by Plant Aging. (United States)

    Lopisso, Daniel Teshome; Knüfer, Jessica; Koopmann, Birger; von Tiedemann, Andreas


    As Verticillium stem striping of oilseed rape (OSR), a vascular disease caused by Verticillium longisporum, is extending into new geographic regions and no control with fungicides exists, the demand for understanding mechanisms of quantitative resistance increases. Because V. longisporum is strictly limited to the xylem and resistance is expressed in the systemic stage post root invasion, we investigated a potential antifungal role of soluble constituents and nutritional conditions in xylem sap as determinants of cultivar resistance of OSR to V. longisporum. Assessment of biometric and molecular genetic parameters applied to describe V. longisporum resistance (net area under disease progress curve, stunting, stem thickness, plant biomass, and V. longisporum DNA content) showed consistent susceptibility of cultivar 'Falcon' in contrast to two resistant genotypes, 'SEM' and 'Aviso'. Spectrophotometric analysis revealed a consistently stronger in vitro growth of V. longisporum in xylem sap extracted from OSR compared with the water control. Further comparisons of fungal growth in xylem sap of different cultivars revealed the absence of constitutive or V. longisporum induced antifungal activity in the xylem sap of resistant versus susceptible genotypes. The similar growth of V. longisporum in xylem sap, irrespective of cultivar, infection with V. longisporum and xylem sap filtration, was correlated with about equal amounts of total soluble proteins in xylem sap from these treatments. Interestingly, compared with younger plants, xylem sap from older plants induced significantly stronger fungal growth. Growth enhancement of V. longisporum in xylem sap of aging plants was reflected by increased contents of carbohydrates, which was consistent in mock or V. longisporum-infected plants and independent from cultivar resistance. The improved nutritional conditions in the xylem of more mature plants may explain the late appearance of disease symptoms, which are observed only in

  14. Finite element simulation and testing of ISW CFRP anchorage

    DEFF Research Database (Denmark)

    Schmidt, Jacob Wittrup; Goltermann, Per; Hertz, Kristian Dahl


    Several Carbon Fibre Reinforced Polymers (CFRP) systems have been used successfully for strengthening of structures during the last decades. However, the fracture often occurs in the concrete adherent or in the adhesive interface when used for steel strengthening. As a consequence the CFRP...... is poorly utilized with a non ductile and brittle failure mode as the outcome. Mechanical anchorage can be used to utilize the full capacity of the CFRP materials but cannot yet challenge systems used for steel. Such systems can be used to transfer stresses from the CFRP material efficiently...

  15. Managing complex orthodontic problems: the use of implants for anchorage. (United States)

    Kokich, V G


    Today implants are commonly used to replace missing teeth in partially edentulous adult orthodontic patients. Because these patients are missing teeth, orthodontic mechanics may be complicated or often impossible because of insufficient anchorage. In these situations, it may be feasible to use the implant initially as an orthodontic anchor to facilitate complex tooth movement and secondarily as an abutment for a crown or fixed prosthesis. This article will discuss the ramifications and requirements for using implants as anchors and abutments in adult orthodontic patients.

  16. Mammary tumors that become independent of the type I insulin-like growth factor receptor express elevated levels of platelet-derived growth factor receptors

    Directory of Open Access Journals (Sweden)

    Campbell Craig I


    Full Text Available Abstract Background Targeted therapies are becoming an essential part of breast cancer treatment and agents targeting the type I insulin-like growth factor receptor (IGF-IR are currently being investigated in clinical trials. One of the limitations of targeted therapies is the development of resistant variants and these variants typically present with unique gene expression patterns and characteristics compared to the original tumor. Results MTB-IGFIR transgenic mice, with inducible overexpression of the IGF-IR were used to model mammary tumors that develop resistance to IGF-IR targeting agents. IGF-IR independent mammary tumors, previously shown to possess characteristics associated with EMT, were found to express elevated levels of PDGFRα and PDGFRβ. Furthermore, these receptors were shown to be inversely expressed with the IGF-IR in this model. Using cell lines derived from IGF-IR-independent mammary tumors (from MTB-IGFIR mice, it was demonstrated that PDGFRα and to a lesser extent PDGFRβ was important for cell migration and invasion as RNAi knockdown of PDGFRα alone or PDGFRα and PDGFRβ in combination, significantly decreased tumor cell migration in Boyden chamber assays and suppressed cell migration in scratch wound assays. Somewhat surprisingly, concomitant knockdown of PDGFRα and PDGFRβ resulted in a modest increase in cell proliferation and a decrease in apoptosis. Conclusion During IGF-IR independence, PDGFRs are upregulated and function to enhance tumor cell motility. These results demonstrate a novel interaction between the IGF-IR and PDGFRs and highlight an important, therapeutically relevant pathway, for tumor cell migration and invasion.

  17. Comparative photoelastic study of dental and skeletal anchorages in the canine retraction

    Directory of Open Access Journals (Sweden)

    Cristiane Aparecida de Assis Claro


    Full Text Available OBJECTIVE: To compare dental and skeletal anchorages in mandibular canine retraction by means of a stress distribution analysis. METHODS: A photoelastic model was produced from second molar to canine, without the first premolar, and mandibular canine retraction was simulated by a rubber band tied to two types of anchorage: dental anchorage, in the first molar attached to adjacent teeth, and skeletal anchorage with a hook simulating the mini-implant. The forces were applied 10 times and observed in a circular polariscope. The stresses located in the mandibular canine were recorded in 7 regions. The Mann-Whitney test was employed to compare the stress in each region and between both anchorage systems. The stresses in the mandibular canine periradicular regions were compared by the Kruskal-Wallis test. RESULTS: Stresses were similar in the cervical region and the middle third. In the apical third, the stresses associated with skeletal anchorage were higher than the stresses associated with dental anchorage. The results of the Kruskal-Wallis test showed that the highest stresses were identified in the cervical-distal, apical-distal, and apex regions with the use of dental anchorage, and in the apical-distal, apical-mesial, cervical-distal, and apex regions with the use of skeletal anchorage. CONCLUSIONS: The use of skeletal anchorage in canine retraction caused greater stress in the apical third than the use of dental anchorage, which indicates an intrusive component resulting from the direction of the force due to the position of the mini-implant and the bracket hook of the canine.

  18. An evaluation of density-dependent and density-independent influences on population growth rates in Weddell seals (United States)

    Rotella, J.J.; Link, W.A.; Nichols, J.D.; Hadley, G.L.; Garrott, R.A.; Proffitt, K.M.


    Much of the existing literature that evaluates the roles of density-dependent and density-independent factors on population dynamics has been called into question in recent years because measurement errors were not properly dealt with in analyses. Using state-space models to account for measurement errors, we evaluated a set of competing models for a 22-year time series of mark-resight estimates of abundance for a breeding population of female Weddell seals (Leptonychotes weddellii) studied in Erebus Bay, Antarctica. We tested for evidence of direct density dependence in growth rates and evaluated whether equilibrium population size was related to seasonal sea-ice extent and the Southern Oscillation Index (SOI). We found strong evidence of negative density dependence in annual growth rates for a population whose estimated size ranged from 438 to 623 females during the study. Based on Bayes factors, a density-dependence-only model was favored over models that also included en! vironmental covariates. According to the favored model, the population had a stationary distribution with a mean of 497 females (SD = 60.5), an expected growth rate of 1.10 (95% credible interval 1.08-1.15) when population size was 441 females, and a rate of 0.90 (95% credible interval 0.87-0.93) for a population of 553 females. A model including effects of SOI did receive some support and indicated a positive relationship between SOI and population size. However, effects of SOI were not large, and including the effect did not greatly reduce our estimate of process variation. We speculate that direct density dependence occurred because rates of adult survival, breeding, and temporary emigration were affected by limitations on per capita food resources and space for parturition and pup-rearing. To improve understanding of the relative roles of various demographic components and their associated vital rates to population growth rate, mark-recapture methods can be applied that incorporate both

  19. 49 CFR 393.93 - Seats, seat belt assemblies, and seat belt assembly anchorages. (United States)


    ... 49 Transportation 5 2010-10-01 2010-10-01 false Seats, seat belt assemblies, and seat belt... § 393.93 Seats, seat belt assemblies, and seat belt assembly anchorages. (a) Buses—(1) Buses... the driver's seat and seat belt assembly anchorages that conform to the location and...

  20. 76 FR 15246 - Anchorage Regulations; Narragansett Bay and Rhode Island Sound, RI (United States)


    ... Sound, RI AGENCY: Coast Guard, DHS. ACTION: Notice of proposed rulemaking. SUMMARY: The Coast Guard... an offshore anchorage in Rhode Island Sound south of Brenton Point, Rhode Island, for use by vessels... Sound that under current informal practice is routinely used by mariners as an anchorage while waiting...

  1. 78 FR 9811 - Anchorages; Captain of the Port Puget Sound Zone, WA (United States)


    ... area with a radius of 600 yards, having its center at 48 31'09'' N, 122 34'55'' W. (11) Cap Sante Tug and Barge General Anchorage. The Cap Sante Tug and Barge General Anchorage includes all waters... northeast tip of Cap Sante; then southeast to 48 30'53'' N, 122 35'28'' W; then west southwest to 48...

  2. 33 CFR 110.189a - Key West Harbor, Key West, Fla., naval explosives anchorage area. (United States)


    ..., Key West, Fla., naval explosives anchorage area. (a) The anchorage ground. A circular area with its center at latitude 24°30′50.6″, longitude 81°50′31.6″ with a radius of 300 yards, for use for ammunition exceeding the prescribed limits for pier-side handling. (b) The regulations. (1) When occupied by a...

  3. Flexural Strengthening of RC Slabs with Prestressed CFRP Strips Using Different Anchorage Systems

    Directory of Open Access Journals (Sweden)

    José Sena-Cruz


    Full Text Available Externally Bonded Reinforcement (EBR technique has been widely used for flexural strengthening of concrete structures by using carbon fiber-reinforced polymers (CFRP. EBR technique offers several structural advantages when the CFRP material is prestressed. This paper presents an experimental and numerical study on reinforced (RC slabs strengthened in flexure with prestressed CFRP strips as a structural strengthening system. The strips are applied as an externally bonded reinforcement (EBR and anchored with either a mechanical or a gradient anchorage. The former foresees metallic anchorage plates fixed to the concrete substrate, while the latter is based on an accelerated epoxy resin curing followed by a segment-wise prestress force decrease at the strip ends. Both anchorage systems, in combination with different CFRP strip geometries, were subjected to static loading tests. It could be demonstrated that the composite strip’s performance is better exploited when prestressing is used, with slightly higher overall load carrying capacities for mechanical anchorages than for the gradient anchorage. The performed investigations by means of a cross-section analysis supported the experimental observation that in case a mechanical anchorage is used, progressive strip debonding changes the fully bonded configuration to an unbonded end-anchored system. The inclusion of defined debonding criteria for both the anchorage zones and free length between the anchorage regions allowed to precisely capture the ultimate loading forces.

  4. Treatment of a Class II deepbite with microimplant anchorage. (United States)

    Park, Hyo-Sang; Kim, Ji-Yeun; Kwon, Tae-Geon


    The goal of this report was to illustrate new treatment mechanics for using microimplants for the treatment of a Class II Division 2 deepbite malocclusion. A 29-year-old woman with a deepbite was treated with the aid of microimplant anchorage. Microimplants placed between the maxillary second premolars and first molars were used as anchorage to apply a distal force to the anterior teeth to correct the Class II canine and molar relationships. A distal force was applied to long hooks that were crimped between the lateral incisors and the canines. By applying a backward force to the long hooks, the maxillary anterior teeth experienced palatal root movement with no change in the vertical and anteroposterior positions of the incisal edges. The distal extrusive movement of the maxillary second molars achieved by disengaging the second molars from the archwire during distal force application and an anterior bite-block bonded on the lingual surface of the maxillary central incisors produced the increase in vertical dimension. The distal force to the long extended hooks from the microimplants was possibly good mechanics for obtaining the palatal root movement and correcting the Class II canine and molar relationships. The anterior bite-block and disengagement of the maxillary second molars during distal force application were effective for increasing the vertical dimension.

  5. Summary of Quaternary geology of the Municipality of Anchorage, Alaska (United States)

    Schmoll, H.R.; Yehle, L.A.; Updike, R.G.


    Quaternary geology of the Upper Cook Inlet region is dominated by deposits of glacier retreats that followed repeated advances from both adjacent and more distant mountains. At several levels high on the mountains, there are remnant glacial deposits and other features of middle or older Pleistocene age. Late Pleistocene lateral moraines along the Chugach Mountain front represent successively younger positions of ice retreat from the last glacial maximum. As the trunk glacier retreated northeastward up the Anchorage lowland, Cook Inlet transgressed the area, depositing the Bootlegger Cove Formation and Tudor Road deposits. The glacier then readvanced to form the latest Pleistocene Elmendorf Moraine, a prominent feature that trends across the Anchorage lowland. Extensive alluvium was deposited both concurrently and somewhat later as Cook Inlet regressed. Mountain valleys contain (1) locally preserved moraines possibly of early Holocene age; (2) poorly preserved moraine remnants of older late Holocene age; and (3) well-preserved moraines formed mainly during the Little Ice Age. Glaciers still occupy large parts of the mountains, the upper ends of some mountain valleys, and small cirques. Holocene landslide deposits, including those formed during the great Alaska earthquake of 1964, occur throughout the area, especially along bluffs containing the Bootlegger Cove Formation.

  6. Evaluation of dredged material proposed for ocean disposal from Gravesend Bay Anchorage, New York

    Energy Technology Data Exchange (ETDEWEB)

    Barrows, E.S.; Gruendell, B.D. [Battelle/Marine Sciences Lab., Sequim, WA (United States)


    The Gravesend Bay Anchorage was one of seven waterways that the US Army Corps of Engineers-New York District (USACE-NYD) requested the Battelle Marine Sciences Laboratory (MSL) to sample and evaluate for dredging and disposal in February 1994. Sediment samples were submitted for physical and chemical analyses to provide baseline sediment chemistry data on the Gravesend Bay Anchorage. Individual sediment core samples collected at the Gravesend Bay Anchorage were analyzed for grain size, moisture content, and total organic carbon (TOC). Two samples, one of composited sediment cores representing the southeast corner of the anchorage (COMP GR), and one sediment core representing the northeast corner of the anchorage (Station GR-1 0), were analyzed for bulk density, specific gravity, metals, chlorinated pesticides, polychlorinated biphenyl (PCB) congeners, polynuclear aromatic hydrocarbons (PAH), and 1,4-dichlorobenzene.

  7. Mini-Implants in the Anchorage Armamentarium: New Paradigms in the Orthodontics

    Directory of Open Access Journals (Sweden)

    Masaru Yamaguchi


    Full Text Available Paradigms have started to shift in the orthodontic world since the introduction of mini-implants in the anchorage armamentarium. Various forms of skeletal anchorage, including miniscrews and miniplates, have been reported in the literature. Recently, great emphasis has been placed on the miniscrew type of temporary anchorage device (TAD. These devices are small, are implanted with a relatively simple surgical procedure, and increase the potential for better orthodontic results. Therefore, miniscrews not only free orthodontists from anchorage-demanding cases, but they also enable clinicians to have good control over tooth movement in 3 dimensions. The miniplate type also produces significant improvements in treatment outcomes and has widened the spectrum of orthodontics. The purpose of this paper is to update clinicians on the current concepts and versatile uses and clinical applications of skeletal anchorage in orthodontics.

  8. Mini-Implants in the Anchorage Armamentarium: New Paradigms in the Orthodontics (United States)

    Yamaguchi, Masaru; Inami, Toshihiro; Ito, Ko; Kasai, Kazutaka; Tanimoto, Yasuhiro


    Paradigms have started to shift in the orthodontic world since the introduction of mini-implants in the anchorage armamentarium. Various forms of skeletal anchorage, including miniscrews and miniplates, have been reported in the literature. Recently, great emphasis has been placed on the miniscrew type of temporary anchorage device (TAD). These devices are small, are implanted with a relatively simple surgical procedure, and increase the potential for better orthodontic results. Therefore, miniscrews not only free orthodontists from anchorage-demanding cases, but they also enable clinicians to have good control over tooth movement in 3 dimensions. The miniplate type also produces significant improvements in treatment outcomes and has widened the spectrum of orthodontics. The purpose of this paper is to update clinicians on the current concepts and versatile uses and clinical applications of skeletal anchorage in orthodontics. PMID:22719763

  9. [Clinical stability of immediate load of domestic micro-titanium screws for anchorage in orthodontics]. (United States)

    Zheng, Qing-zhong; Xie, Xing-qian; Xie, Xue-mei; Wang, Jian; Yu, Xiao-jia


    To investigate the immediate load stability of domestic micro-titanium screws for anchorage in orthodontics. Adult orthodontic patients needing the greatest anchorage were included in the study. Domestic micro-titanium screws were used to be orthodontic anchorage, immediate implantation and loading were conducted. A total of 52 implants of domestic micro-titanium anchorage in 20 patients were used. Forty-seven implants were successful in 20 patients,5 failed. The total loading time was 3-8 months. Domestic micro-titanium implant screws for anchorage can meet the needs of clinical orthodontics. However, immediate loading results in 10.4% failure rate, especially for the implant with a diameter of 1.2mmx7mm. Supported by Science and Technology Development Foundation of Fengxian District, Shanghai Municipality (Grant No. 090602).

  10. Inhibition of bacterial growth in sweet cheese whey by carbon dioxide as determined by culture-independent community profiling. (United States)

    Lo, Raquel; Xue, Tian; Weeks, Mike; Turner, Mark S; Bansal, Nidhi


    Whey is a valuable co-product from cheese making that serves as a raw material for a wide range of products. Its rich nutritional content lends itself to rapid spoilage, thus it typically needs to be pasteurised and refrigerated promptly. Despite the extensive literature on milk spoilage bacteria, little is known about the spoilage bacteria of whey. The utility of carbon dioxide (CO2) to extend the shelf-life of raw milk and cottage cheese has been well established, but its application in whey preservation has not yet been explored. This study aims to characterise the microbial populations of fresh and spoiled sweet whey by culture-independent community profiling using 454 pyrosequencing of 16S rRNA gene amplicons and to determine whether carbonation is effective in inhibiting bacterial growth in sweet whey. The microbiota of raw Cheddar and Mozzarella whey was dominated by cheese starter bacteria. After pasteurisation, two out of the three samples studied became dominated by diverse environmental bacteria from various phyla, with Proteobacteria being the most dominant. Diverse microbial profiles were maintained until spoilage occurred, when the entire population was dominated by just one or two genera. Whey spoilage bacteria were found to be similar to those of milk. Pasteurised Cheddar and Mozzarella whey was spoiled by Bacillus sp. or Pseudomonas sp., and raw Mozzarella whey was spoiled by Pseudomonas sp., Serratia sp., and other members of the Enterobacteriaceae family. CO2 was effective in inhibiting bacterial growth of pasteurised Cheddar and Mozzarella whey stored at 15°C and raw Mozzarella whey stored at 4°C. The spoilage bacteria of the carbonated samples were similar to those of the non-carbonated controls.

  11. Cyclooxygenase-2 expression is dependent upon epidermal growth factor receptor expression or activation in androgen independent prostate cancer

    Institute of Scientific and Technical Information of China (English)

    Rui-Peng Jia; Lu-Wei Xu; Qi Su; Jian-Hua Zhao; Wen-Cheng Li; Feng Wang; Zheng Xu


    Aim: To investigate the expression of cyclooxygenase-2 (COX-2) and epidermal growth factor receptor (EGFR) and the possible mechanism in the development in androgen independent prostate cancer (AIPC). Methods: Immunohis- tochemistry was performed on paraffin-embedded sections with goat polyclonal against COX-2 and mouse mono- clonal antibody against EGFR in 30 AIPC and 18 androgen dependent prostate cancer (ADPC) specimens. The effect of epidermal growth factor (EGF) treatments on the expression of COX-2 and signal pathway in PC-3 and DU-145 cells was studied using reverse transcription-polymerase chain reaction (RT-PCR) and Western blot analysis. ELISA was used to measure prostaglandin E2 (PGE2) levels in the media of PC-3 and DU-145 incubated with EGF for 24 h. Results: COX-2 was positively expressed in AIPC and ADPC, which were predominantly in endochylema of prostate cancer (Pca) cells. Intense staining was seen in AIPC (80%) and in ADPC (55.5%), but there was no significant association between the two groups. EGFR expression was also positive in the two groups (61.8% in ADPC and 90% in AIPC, P < 0.01). A significant association was found between EGFR expression and a higher Gleason score (P < 0.05) or tumor stage (P < 0.05). The expression of PGE2 was increased in PC-3 and DU-145 cells after being incubated with EGF. Both p38MAPK and PI-3K pathway were involved in the PC-3 cell COX-2 upregulation course. In DU- 145, only p38MAPK pathway was associated with COX-2 upregulation. Conclusion: EGFR activation induces COX-2 expression through PI-3K and/or p38MAPK pathways. COX-2 and EGFR inhibitors might have a cooperative anti-tumor effect in Pca.

  12. PRIMA-1Met suppresses colorectal cancer independent of p53 by targeting MEK. (United States)

    Lu, Tao; Zou, Yanmei; Xu, Guogang; Potter, Jane A; Taylor, Garry L; Duan, Qiuhong; Yang, Qin; Xiong, Huihua; Qiu, Hong; Ye, Dawei; Zhang, Peng; Yu, Shiying; Yuan, Xianglin; Zhu, Feng; Wang, Yihua; Xiong, Hua


    PRIMA-1Met is the methylated PRIMA-1 (p53 reactivation and induction of massive apoptosis) and could restore tumor suppressor function of mutant p53 and induce p53 dependent apoptosis in cancer cells harboring mutant p53. However, p53 independent activity of PRIMA-1Met remains elusive. Here we reported that PRIMA-1Met attenuated colorectal cancer cell growth irrespective of p53 status. Kinase profiling revealed that mitogen-activated or extracellular signal-related protein kinase (MEK) might be a potential target of PRIMA-1Met. Pull-down binding and ATP competitive assay showed that PRIMA-1Met directly bound MEK in vitro and in cells. Furthermore, the direct binding sites of PRIMA-1Met were explored by using a computational docking model. Treatment of colorectal cancer cells with PRIMA-1Met inhibited p53-independent phosphorylation of MEK, which in turn impaired anchorage-independent cell growth in vitro. Moreover, PRIMA-1Met suppressed colorectal cancer growth in xenograft mouse model by inhibiting MEK1 activity.Taken together, our findings demonstrate a novel p53-independent activity of PRIMA-1Met to inhibit MEK and suppress colorectal cancer growth.

  13. 1964 Great Alaska Earthquake: a photographic tour of Anchorage, Alaska (United States)

    Thoms, Evan E.; Haeussler, Peter J.; Anderson, Rebecca D.; McGimsey, Robert G.


    On March 27, 1964, at 5:36 p.m., a magnitude 9.2 earthquake, the largest recorded earthquake in U.S. history, struck southcentral Alaska (fig. 1). The Great Alaska Earthquake (also known as the Good Friday Earthquake) occurred at a pivotal time in the history of earth science, and helped lead to the acceptance of plate tectonic theory (Cox, 1973; Brocher and others, 2014). All large subduction zone earthquakes are understood through insights learned from the 1964 event, and observations and interpretations of the earthquake have influenced the design of infrastructure and seismic monitoring systems now in place. The earthquake caused extensive damage across the State, and triggered local tsunamis that devastated the Alaskan towns of Whittier, Valdez, and Seward. In Anchorage, the main cause of damage was ground shaking, which lasted approximately 4.5 minutes. Many buildings could not withstand this motion and were damaged or collapsed even though their foundations remained intact. More significantly, ground shaking triggered a number of landslides along coastal and drainage valley bluffs underlain by the Bootlegger Cove Formation, a composite of facies containing variably mixed gravel, sand, silt, and clay which were deposited over much of upper Cook Inlet during the Late Pleistocene (Ulery and others, 1983). Cyclic (or strain) softening of the more sensitive clay facies caused overlying blocks of soil to slide sideways along surfaces dipping by only a few degrees. This guide is the document version of an interactive web map that was created as part of the commemoration events for the 50th anniversary of the 1964 Great Alaska Earthquake. It is accessible at the U.S. Geological Survey (USGS) Alaska Science Center website: The website features a map display with suggested tour stops in Anchorage, historical photographs taken shortly after the earthquake, repeat photography of selected sites, scanned documents

  14. [Retracted] Epidermal growth factor-stimulated human cervical cancer cell growth is associated with EGFR and cyclin D1 activation, independent of COX-2 expression levels. (United States)

    Narayanan, Rajkishen; Kim, Hye Na; Narayanan, Narayanan K; Nargi, Dominick; Narayanan, Bhagavathi


    Following the publication of this article, which was concerned with the expression of phosphorylated epidermal growth factor receptor (pEGFR) and cyclin D1 activation independently of the expression levels of cyclo-oxygenase-2, an interested reader drew to our attention apparent anomalies associated with the western blot data shown in Fig. 2C. Following an internal investigation at the New York University School of Medicine, we were requested to produce the original film, or the scan of the image of the film, for verification. Unfortunately, we were unable to provide the original film or scanned image to disprove the allegation, since the original pEGFR image could not be found. Therefore, the Investigation Committee recommended that this article be retracted, and we are withdrawing the article in line with the request. All the authors agree to the retraction of this paper. We sincerely regret any inconvenience this has caused. [the original article was published in the International Journal of Oncology 40: 13-20, 2012; DOI: 10.3892/ijo.2011.1211].

  15. Transforming growth factor-β1/Smad3-independent epithelial–mesenchymal transition in type I collagen glomerulopathy

    Directory of Open Access Journals (Sweden)

    Brodeur AC


    Full Text Available Amanda C Brodeur,1–3 Anna M Roberts-Pilgrim,3 Kimberlee L Thompson,1 Craig L Franklin,4 Charlotte L Phillips2,3 1Department of Biomedical Sciences, Missouri State University, Springfield, MO, USA; 2Department of Child Health, University of Missouri, Columbia, MO, USA; 3Department of Biochemistry, University of Missouri, Columbia, MO, USA; 4Department of Veterinary Pathobiology, University of Missouri, Columbia, MO, USA Abstract: The glomerulofibrotic Col1a2-deficient mouse model demonstrates glomerular homotrimeric type I collagen deposition in mesangial and subendothelial spaces. In this report, we investigate the role of transforming growth factor β1 (TGF-β1 in myofibroblast activation and epithelial–mesenchymal transition (EMT in this glomerulopathy. Immunohistochemical analyses of glomerular α-sma, desmin, vimentin, and proliferating cell nuclear antigen demonstrated parietal epithelial cell proliferation and EMT in late stages of the glomerulopathy in the Col1a2-deficient mice. Glomerular TGF-β1 RNA and protein were not elevated in 1- and 3-month-old mice as determined by quantitative reverse transcriptase-polymerase chain reaction and protein immunoassay analyses. To investigate further whether TGF-β1 plays a role in the glomerulopathy outside of the 1- and 3-month time periods, the Col1a2-deficient mice were bred with Smad3 knockout mice. If the glomerular fibrosis in the Col1a2-deficient mice is mediated by the TGF-β1/Smad3 transcription pathway, it was hypothesized that the resultant Col1a2-deficient/Smad3-deficient mice would exhibit attenuated glomerular homotrimer deposition. However, the Col1a2-deficient/Smad3-deficient kidneys were similarly affected as compared to age-matched Col1a2-deficient kidneys, suggesting that homotrimeric type I collagen deposition in the Col1a2-deficient mouse is independent of TGF-β1/Smad3 signaling. Deposition of homotrimeric type I collagen appears to be the initiating event in this

  16. Numerical Analysis of Quality Inspection of Anchorage System

    Institute of Scientific and Technical Information of China (English)

    ZHANGYongxing; XUMing


    Sonoprobe method has been applied in non-destructive inspection of anchorage project.The fundament is that dynamic transient excitation causes the elastic vibration of an anchor bar,and flaws can be estimated or deduced by determining transient response of the anchor bar.FEA numeric solution of hyperbolic equation indicates that deductions must comply with acoustic parameters such as velocity of sound,vibration range,wave shape etc when inspecting interior flaws in the grout of an anchor bar,Based on wavelet packet analysis,the energy eigenvector is a flaw vector,which could be regarded as the basis in the nondestructive inspection of anchors,As a non-linear dynamical system,artifical neural networks dealing with quality insection of gray system have been proved efficient.

  17. Regulation of P21cip1 Expression by Growth Factors and the Extracellular Matrix Reveals a Role for Transient ERK Activity in G1 Phase (United States)

    Bottazzi, Maria Elena; Zhu, Xiaoyun; Böhmer, Ralph M.; Assoian, Richard K.


    We have examined the regulation of p21cip1 by soluble mitogens and cell anchorage as well as the relationship between the expression of p21cip1 and activation of the ERK subfamily of MAP kinases. We find that p21cip1 expression in G1 phase can be divided into two discrete phases: an initial induction that requires growth factors and the activation of ERK, and then a subsequent decline that is enhanced by cell anchorage in an ERK-independent manner. In contrast to the induction of cyclin D1, the induction of p21cip1 is mediated by transient ERK activity. Comparative studies with wild-type and p21cip1-null fibroblasts indicate that adhesion-dependent regulation of p21cip1 is important for proper control of cyclin E–cdk2 activity. These data lead to a model in which mitogens and anchorage act in a parallel fashion to regulate G1 phase expression of p21cip1. They also show that (a) growth factors and growth factor/extracellular matrix cooperation can have different roles in regulating G1 phase ERK activity and (b) both transient and sustained ERK signals have functionally significant roles in controlling cell cycle progression through G1 phase. PMID:10491389

  18. Comparison of Anchorage Pattern under Two Types of Orthodontic Mini- Implant Loading During Retraction in Type A Anchorage Cases (United States)

    Khan, B. Imran; Mandava, Prasad; Reddy, G. Vivek; Nettam, Venkatesh; Bhavikati, Venkat Naidu


    Introduction The orthodontic mini-screws are the mainstay of direct skeletal anchorage which requires minimal compliance and provides maximal anchorage control. However, the timing of initiation of orthodontic loading of these mini-screws is not clearly established in the available studies. Aim The purpose of this study was to determine the reciprocal effects on mini-screw implant with immediate loading in comparison to that of delayed loading during retraction. Materials and Methods The prospective clinical study included a sample of 25 orthodontic patients in the age range of 18-25 years. All the cases were of bi-maxillary proclination with Type-A anchorage demands. All the first premolars were indicated for extraction. A split mouth technique for each patient was utilized by loading mini-implant immediately after its placement on one side and the opposite side implant was loaded after a time lag of two weeks post-insertion. Retraction force of 150g was applied for three months on each side. The displacement of the head and tail of the implant, molar anterior tooth retraction was measured on Orthopantomograph (OPG) taken at T1 (initial) and T2 (after three months). A grid method with each 1mm magnified to 500 pixels was superimposed on OPG and the relative displacements were evaluated. Student’s unpaired ‘t’ test was used for comparison between left and right side and paired ‘t’ test for the parameters on the same side. The p-value equal to or less than 0.05 was taken as statistically significant. Results The mean displacement of head of the implant on the immediate loading is 0.57mm where as the tail exhibited 0.75 mm. The head and tail of the implant on the delayed loading displaced by 0.35mm and 0.38mm respectively, on an average when data was analysed. Significant difference between the two types of loading was noted. Conclusion Delayed loading is beneficial as compared to immediate loading during extraction space closure. PMID:27891469

  19. Exterior beam-column joint study with non-conventional reinforcement detailing using mechanical anchorage under reversal loading

    Indian Academy of Sciences (India)

    S Rajagopal; S Prabavathy


    Reinforced concrete structures beam-column joints are the most critical regions in seismic prone areas. Proper reinforcement anchorage is essential to enhance the performance of the joints. An attempt has been made to appraise the performance of the anchorages and joints. The anchorages are detailed as per ACI-352 (mechanical anchorages), ACI-318 (conventional bent hooks) and IS-456 (conventional full anchorage). The joints are detailed without confinement in group-I and with additional X-cross bar in group-II. To assess the seismic performance, the specimens are assembled into two groups of three specimens each and were tested under reversal loading, The specimen with T-type mechanical anchorage (Headed bar) and T-type mechanical anchorage combination with X-cross bar exhibited significant improvement in seismic performance: load-displacement capacity, displacement ductility, stiffness degradation, controlled crack capacity in the joint shear panel and also reduced congestion of reinforcement in joint core.

  20. Met-Independent Hepatocyte Growth Factor-mediated regulation of cell adhesion in human prostate cancer cells

    Directory of Open Access Journals (Sweden)

    Davis Rodney


    Full Text Available Abstract Background Prostate cancer cells communicate reciprocally with the stromal cells surrounding them, inside the prostate, and after metastasis, within the bone. Each tissue secretes factors for interpretation by the other. One stromally-derived factor, Hepatocyte Growth Factor (HGF, was found twenty years ago to regulate invasion and growth of carcinoma cells. Working with the LNCaP prostate cancer progression model, we found that these cells could respond to HGF stimulation, even in the absence of Met, the only known HGF receptor. The new HGF binding partner we find on the cell surface may help to clarify conflicts in the past literature about Met expression and HGF response in cancer cells. Methods We searched for Met or any HGF binding partner on the cells of the PC3 and LNCaP prostate cancer cell models, using HGF immobilized on agarose beads. By using mass spectrometry analyses and sequencing we have identified nucleolin protein as a novel HGF binding partner. Antibodies against nucleolin (or HGF were able to ameliorate the stimulatory effects of HGF on met-negative prostate cancer cells. Western blots, RT-PCR, and immunohistochemistry were used to assess nucleolin levels during prostate cancer progression in both LNCaP and PC3 models. Results We have identified HGF as a major signaling component of prostate stromal-conditioned media (SCM and have implicated the protein nucleolin in HGF signal reception by the LNCaP model prostate cancer cells. Antibodies that silence either HGF (in SCM or nucleolin (on the cell surfaces eliminate the adhesion-stimulatory effects of the SCM. Likewise, addition of purified HGF to control media mimics the action of SCM. C4-2, an LNCaP lineage-derived, androgen-independent human prostate cancer cell line, responds to HGF in a concentration-dependent manner by increasing its adhesion and reducing its migration on laminin substratum. These HGF effects are not due to shifts in the expression levels of

  1. Cellular Internalization of Fibroblast Growth Factor-12 Exerts Radioprotective Effects on Intestinal Radiation Damage Independently of FGFR Signaling

    Energy Technology Data Exchange (ETDEWEB)

    Nakayama, Fumiaki, E-mail: [Advanced Radiation Biology Research Program, Research Center for Charged Particle Therapy, Chiba (Japan); Umeda, Sachiko [Advanced Radiation Biology Research Program, Research Center for Charged Particle Therapy, Chiba (Japan); Yasuda, Takeshi [Radiation Emergency Medicine Research Program, Research Center for Radiation Emergency Medicine, National Institute of Radiological Sciences, Chiba (Japan); Fujita, Mayumi [Advanced Radiation Biology Research Program, Research Center for Charged Particle Therapy, Chiba (Japan); Asada, Masahiro [Signaling Molecules Research Group, Biomedical Research Institute, National Institute of Advanced Industrial Science and Technology, Tsukuba (Japan); Meineke, Viktor [Bundeswehr Institute of Radiobiology affiliated to the University of Ulm, Munich (Germany); Imamura, Toru [Signaling Molecules Research Group, Biomedical Research Institute, National Institute of Advanced Industrial Science and Technology, Tsukuba (Japan); Imai, Takashi [Advanced Radiation Biology Research Program, Research Center for Charged Particle Therapy, Chiba (Japan)


    Purpose: Several fibroblast growth factors (FGFs) were shown to inhibit radiation-induced tissue damage through FGF receptor (FGFR) signaling; however, this signaling was also found to be involved in the pathogenesis of several malignant tumors. In contrast, FGF12 cannot activate any FGFRs. Instead, FGF12 can be internalized readily into cells using 2 cell-penetrating peptide domains (CPP-M, CPP-C). Therefore, this study focused on clarifying the role of FGF12 internalization in protection against radiation-induced intestinal injury. Methods and Materials: Each FGF or peptide was administered intraperitoneally to BALB/c mice in the absence of heparin 24 hours before or after total body irradiation with γ rays at 9 to 12 Gy. Several radioprotective effects were examined in the jejunum. Results: Administration of FGF12 after radiation exposure was as effective as pretreatment in significantly promoting intestinal regeneration, proliferation of crypt cells, and epithelial differentiation. Two domains, comprising amino acid residues 80 to 109 and 140 to 169 of FGF12B, were identified as being responsible for the radioprotective activity, so that deletion of both domains from FGF12B resulted in a reduction in activity. Interestingly, these regions included the CPP-M and CPP-C domains, respectively; however, CPP-C by itself did not show an antiapoptotic effect. In addition, FGF1, prototypic FGF, possesses a domain corresponding to CPP-M, whereas it lacks CPP-C, so the fusion of FGF1 with CPP-C (FGF1/CPP-C) enhanced cellular internalization and increased radioprotective activity. However, FGF1/CPP-C reduced in vitro mitogenic activity through FGFRs compared with FGF1, implying that FGFR signaling might not be essential for promoting the radioprotective effect of FGF1/CPP-C. In addition, internalized FGF12 suppressed the activation of p38α after irradiation, resulting in reduced radiation-induced apoptosis. Conclusions: These findings indicate that FGF12 can protect the

  2. Urban contaminants project: Data for sediment, fish and eggs collected from Chester Creek, Anchorage, Alaska 1991 (United States)

    US Fish and Wildlife Service, Department of the Interior — Urbanization has degraded the water quality and adversely impacted biological communities in the lakes and streams of Anchorage. Pollution from point and nonpoint...

  3. Comparative efficacy of 2 topical anesthetics for the placement of orthodontic temporary anchorage devices

    National Research Council Canada - National Science Library

    Reznik, Derek S; Jeske, Arthur H; Chen, Jung-Wei; English, Jeryl


    This study compared the effectiveness of topical benzocaine 20% versus a combination of lidocaine, tetracaine, and phenylephrine in providing sufficient analgesia for the placement of orthodontic temporary anchorage devices (TADs...

  4. [A clinical study on the stability of miniscrew anchorage in orthodontics]. (United States)

    Yan, Yong-Qing; Gao, Yi-Ming


    The aim of this retrospective study was to summarize the cases who used miniscrew anchorage and to evaluate the clinical factors influencing the stability of miniscrew. The sample comprised 13 patients with 32 miniscrews, in whom the design, occlusogingival position, alveolar position, loading opportunity, gingival condition were investigated to assess the factors related to stability. The data was analyzed by univariate analysis and multivariate analysis using SAS 10.0 software package. The overall success rate was 90.6%. There was significant relationship between the patients' age and the stability of miniscrews (P=0.04). The success rate was 75% in adolescent patients, and 100% in adult patients. The osseointegration was affected by initial over-loading, but the long-term orthodontic loading (200g) was safe, if osseointegration was achieved. Perio-implant gingivitis, even the suppurative gingivitis (2 cases) didn't destroy the bone-implant interface. The success rate was independent on gender, occlusogingival position, jaw positioning, inserting times of the same miniscrew, and early loading. The primary stability is the crucial factor for long-term stability of the miniscrews.

  5. Transfer and anchorage bond behaviour in self-compacting concrete

    Directory of Open Access Journals (Sweden)

    Rigueira-Víctor, J. W.


    Full Text Available Self-compacting concretes (SCC provide solutions to the problems facing precast concrete construction, enhancing competitiveness, reducing turnaround times and improving final product quality. SCC is fast becoming a key product for the future development of the precast pre-stressed concrete industry.The present paper compares the bond performance of SCC and traditional concrete (TC. The bond performance results confirm the viability of SCC in precast pre-stressed concrete manufacture, despite a slightly higher loss of pre-stressing force and slightly greater anchorage lengths in SCC with a low water/cement ratio. No differences in transfer or anchorage length were detected,however, when high strength TC and SCC were compared. The ECADA test method proved to be well suited to detecting the differences between the concretes analyzed.El desarrollo de los hormigones autocompactantes (SCCofrece muchas posibilidades a las construcciones con hormigón prefabricado, aumentando su competitividad, reduciéndolos plazos de fabricación y ofreciendo mejoras en la calidad del producto final. El SCC se está convirtiendo en un producto clave para el futuro desarrollo de la industria de prefabricados de hormigón pretensado.En este estudio se compara el comportamiento adherente de los SCC con el de los hormigones tradicionales (TC actuales. Los resultados obtenidos confirman la viabilidad del uso de los SCC para la fabricación de elementos prefabricados con hormigón pretensado, en lo relativo a su comportamiento adherente, aunque con la necesidad de considerar unas pérdidas de pretensado ligeramente mayores. Asimismo,debe esperarse un ligero aumento de las longitudes de anclaje cuando se trabaje con SCC de baja relación agua/cemento. Sin embargo, no se han detectado diferencias de comportamiento entre ambos tipos de hormigón cuando la resistencia a compresión es alta en lo relativo a las longitudes de transmisión y anclaje. El método de ensayo ECADA

  6. Mechanical properties and failure characteristics of fractured sandstone with grouting and anchorage

    Institute of Scientific and Technical Information of China (English)

    Zong Yijiang; Han Lijun; Qu Tao; Yang Shengqi


    Based on uniaxial compression experimental results on fractured sandstone with grouting and anchorage, we studied the strength and deformation properties, the failure model, crack formation and evolution laws of fractured sandstone under different conditions of anchorage. The experimental results show that the strength and elastic modulus of fractured sandstone with different fracture angles are sig-nificantly lower than those of intact sandstone. Compared with the fractured samples without anchorage, the peak strength, residual strength, peak and ultimate axial strain of fractured sandstone under different anchorage increase by 64.5-320.0%, 62.8-493.0%, and 31.6-181.4%, respectively. The number of bolts and degree of pre-stress has certain effects on the peak strength and failure model of fractured sandstone. The peak strength of fractured sandstone under different anchorage increases to some extent, and the failure model of fractured sandstone also transforms from tensile failure to tensile-shear mixed failure with the number of bolts. The pre-stress can restrain the formation and evolution process of tensile cracks, delay the failure process of fractured sandstone under anchorage and impel the transformation of failure model from brittle failure to plastic failure.

  7. Progressive transfusion and growth factor independence with adjuvant sertraline in low risk myelodysplastic syndrome treated with an erythropoiesis stimulating agent and granulocyte-colony stimulating factor

    Directory of Open Access Journals (Sweden)

    Kirtan Nautiyal


    Full Text Available Refractoriness to growth factor therapy is commonly associated with inferior outcome in patients with low-risk myelodysplastic syndrome (LR-MDS who require treatment for cytopenias. However, the mechanisms leading to refractoriness are unknown. Here we describe a clinically depressed 74-year-old male with refractory cytopenia with multilineage dysplasia (RCMD and documented growth factor refractory anemia after erythropoeisis stimulating agent (ESA therapy, who attained transfusion and growth factor independence after the addition of sertraline to his medication regimen. Our case demonstrates hematological improvement-erythroid (HI-E in growth factor refractory, low risk MDS and highlights a potential mechanistic link between common inflammatory diseases and LR-MDS.

  8. Are temporary anchorage devices truly effective in the treatment of skeletal open bites? (United States)

    Turkkahraman, Hakan; Sarioglu, Mehmet


    Objective: The aims of this study were to evaluate the effects of temporary anchorage devices (TADs) in the treatment of skeletal open bites and to compare the results with untreated controls. Materials and Methods: A total of forty patients with skeletal anterior open bites were assigned to two groups of twenty each. The mean chronological age for the treatment group (14 female, 6 male) was 16.68 ± 2.80 years old, compared with 16.63 ± 2.83 years old for the control group (11 female, 9 male). Titanium miniplates fixed bilaterally to the infrazygomatic crest area were used as TADs and intrusive forces were applied to the posterior teeth with Ni-Ti coil springs. The treatment and normal growth changes were evaluated using 24 measurements (2 angular, 22 linear). Results: Statistically significant differences were found between the groups in Bx, By, Sn/GoGn, Ax-Bx, U6x, U6y, overjet, overbite, SN/OccP, N-Me, Ans-Me, S-Go/N-Me, interpremolar width, and intermolar width (P < 0.05). In the treatment group, statistically significant upper molar intrusion (mean ± standard deviation [SD], 3.59 ± 1.34; 95% confidence interval [CI], 2.96–4.22), posterior rotation of the occlusal plane (mean ± SD, 3.42 ± 2.17; 95% CI, 2.39–4.43), anterior rotation of the mandible (mean ± SD, 2.25 ± 1.91; 95% CI, 1.36–3.14), and resultant overbite improvement (mean ± SD, 4.82 ± 1.53; 95% CI, 4.10–5.53) were found (P < 0.05). Conclusions: Mild to moderate skeletal anterior open bites could easily be treated with TADs without orthognathic surgery. With the rigid anchorage of miniplates, true molar intrusion of up to 4 mm was achieved. With molar intrusion, anterior rotation of the mandible and a significant reduction in anterior face height were determined. PMID:28042256

  9. Microbeads and anchorage-dependent eukaryotic cells: the beginning of a new era in biotechnology. (United States)

    Miller, A O; Menozzi, F D; Dubois, D


    Modern methods for the mass cultivation of anchorage-dependent mammalian cells started with the advent of microcarrier technology. Largely for reasons pertaining to their mode of preparation and ease of cultivation, 150-230 microns microbeads have been overwhelmingly adopted and the technology around them developed. To meet high biomass, macroporous microbeads have been developed. Also, the chemistry of the microsupport has been adapted in order to afford better protection of fragile cells to mechanical wear while simultaneously reorienting their differentiation towards the sought aims (production of cytokines, enzymes etc. ...). Future progress depends upon solutions being brought to problems inherent to this new technology (maintenance of steady state conditions of growth etc. ...) as well as to requirements arising from animal cell culture in general (biosensors, bioreactor's design etc. ...). Besides such technical implementations, biology at large is also expected to benefit from the advent of microcarriers in fields as diverse as the preparation of metaphasic chromosomes in bulk, toxicity testing, organ reconstitution following cell transplantation etc.

  10. Virtual planning for vertical control using temporary anchorage devices

    Directory of Open Access Journals (Sweden)

    Mauricio Accorsi


    Full Text Available The new and innovative technologies are unprecedentedly improving the level of proficiency in orthodontics in the recent history of this area of expertise. The proliferation of advances, such as self-ligating systems, temporary anchorage devices, shape-memory wires, robotically wire bending, intraoral scanners, cone-beam computed tomography, bring the virtual planning, and confection of dental devices through CAD/CAM systems to the real world. In order to get efficiency and efficacy in orthodontics with these new technologies, we must understand the importance of systemically managed clinical information, medical, and dentistry history of the patients, including the images resources, which ensures the use of a communication that is assisted by the technology, with an interdisciplinary team so that the database is able to help and support the process of therapeutic decision-making. This paper presents the clinical case of a borderline patient for orthognathic surgery who had his final treatment planning supported by these new tools for three-dimensional diagnosis and virtual planning.

  11. Isolated scaphotrapeziotrapezoid osteoarthritis treatment using resurfacing arthroplasty with scaphoid anchorage. (United States)

    Humada Álvarez, G; Simón Pérez, C; García Medrano, B; Faour Martín, O; Marcos Rodríguez, J J; Vega Castrillo, A; Martín Ferrero, M A


    The aim of this study is to show the results of scaphotrapeziotrapezoid (STT) joint osteoarthritis treatment performing resurfacing arthroplasty with scaphoid anchorage. An observational, descriptive and retrospective study was performed. Ten patients with isolated STT joint osteoarthritis were studied between 2013 and 2015. The mean follow-up time was 26months. Clinical results, functional and subjective scores were reviewed. The patients were satisfied, achieving an average of 2.1 (0-3) on the VAS score and 16 (2 to 28) in the DASH questionnaire, and returning to work in the first three months post-surgery. Recovery of range of motion compared to the contralateral wrist was 96% in extension, 95% in flexion, 87% in ulnar deviation and 91% in radial deviation. The average handgrip strength of the wrist was 95% and pinch strength was 95% compared to the contralateral side. There were no intraoperative complications or alterations in postoperative carpal alignment. Resurfacing arthroplasty is proposed as a good and novel alternative in treating isolated SST joint arthritis. Achieving the correct balance between the strength and mobility of the wrist, without causing carpal destabilisation, is important to obtain satisfactory clinical and functional results. Copyright © 2017. Publicado por Elsevier España, S.L.U.

  12. Maps showing seismic landslide hazards in Anchorage, Alaska (United States)

    Jibson, Randall W.


    The devastating landslides that accompanied the great 1964 Alaska earthquake showed that seismically triggered landslides are one of the greatest geologic hazards in Anchorage. Maps quantifying seismic landslide hazards are therefore important for planning, zoning, and emergency-response preparation. The accompanying maps portray seismic landslide hazards for the following conditions: (1) deep, translational landslides, which occur only during great subduction-zone earthquakes that have return periods of =300-900 yr; (2) shallow landslides for a peak ground acceleration (PGA) of 0.69 g, which has a return period of 2,475 yr, or a 2 percent probability of exceedance in 50 yr; and (3) shallow landslides for a PGA of 0.43 g, which has a return period of 475 yr, or a 10 percent probability of exceedance in 50 yr. Deep, translational landslide hazards were delineated based on previous studies of such landslides, with some modifications based on field observations of locations of deep landslides. Shallow-landslide hazards were delineated using a Newmark-type displacement analysis for the two probabilistic ground motions modeled.

  13. Interactions with Astroglia Influence the Shape of the Developing Dendritic Arbor and Restrict Dendrite Growth Independent of Promoting Synaptic Contacts (United States)

    Farley, Jennifer R.; Sterritt, Jeffrey R.; Crane, Andrés B.; Wallace, Christopher S.


    Astroglia play key roles in the development of neurons, ranging from regulating neuron survival to promoting synapse formation, yet basic questions remain about whether astrocytes might be involved in forming the dendritic arbor. Here, we used cultured hippocampal neurons as a simple in vitro model that allowed dendritic growth and geometry to be analyzed quantitatively under conditions where the extent of interactions between neurons and astrocytes varied. When astroglia were proximal to neurons, dendrites and dendritic filopodia oriented toward them, but the general presence of astroglia significantly reduced overall dendrite growth. Further, dendritic arbors in partial physical contact with astroglia developed a pronounced pattern of asymmetrical growth, because the dendrites in direct contact were significantly smaller than the portion of the arbor not in contact. Notably, thrombospondin, the astroglial factor shown previously to promote synapse formation, did not inhibit dendritic growth. Thus, while astroglia promoted the formation of presynaptic contacts onto dendrites, dendritic growth was constrained locally within a developing arbor at sites where dendrites contacted astroglia. Taken together, these observations reveal influences on spatial orientation of growth as well as influences on morphogenesis of the dendritic arbor that have not been previously identified. PMID:28081563

  14. Expression of Gli1 correlates with the transition of breast cancer cells to estrogen-independent growth. (United States)

    Zhao, Jieying; Chen, Guangchun; Cao, Dongmei; Li, Yidong; Diao, Fei; Cai, Haoyu; Jin, Yiduo; Lu, Jian


    The failure of breast cancer treatment is largely due to the development of estrogen independence. Current data illustrate that Hedgehog (Hh) signaling may play an important role in breast cancer development. Here, we show that the expression of the Hh effector protein, Gli1 was significantly higher in estrogen-independent breast cancer cells than in estrogen-dependent cells. Our data showed for the first time that stable expression of Gli1 in ER positive breast cancer cell lines MCF-7 and T47D can induce estrogen-independent proliferation and promote G1/S phase transition, which associated with cyclin-Rb axi. Gli1 can also attenuate the response of proliferation to estrogenic stimulation, which was correlated with down-regulation of expression of ERalpha and PR, as well as down-regulation of transactivation of ERalpha. Our results suggest that up-regulation of Gli1 in breast cancer cells may be one of the mechanisms responsible for developing estrogen independence and this process may be regulated through down-regulation of expression and transactivation of ERalpha.

  15. Picropodophyllin causes mitotic arrest and catastrophe by depolymerizing microtubules via insulin-like growth factor-1 receptor-independent mechanism. (United States)

    Waraky, Ahmed; Akopyan, Karen; Parrow, Vendela; Strömberg, Thomas; Axelson, Magnus; Abrahmsén, Lars; Lindqvist, Arne; Larsson, Olle; Aleem, Eiman


    Picropodophyllin (PPP) is an anticancer drug undergoing clinical development in NSCLC. PPP has been shown to suppress IGF-1R signaling and to induce a G2/M cell cycle phase arrest but the exact mechanisms remain to be elucidated. The present study identified an IGF-1-independent mechanism of PPP leading to pro-metaphase arrest. The mitotic block was induced in human cancer cell lines and in an A549 xenograft mouse but did not occur in normal hepatocytes/mouse tissues. Cell cycle arrest by PPP occurred in vitro and in vivo accompanied by prominent CDK1 activation, and was IGF-1R-independent since it occurred also in IGF-1R-depleted and null cells. The tumor cells were not arrested in G2/M but in mitosis. Centrosome separation was prevented during mitotic entry, resulting in a monopolar mitotic spindle with subsequent prometaphase-arrest, independent of Plk1/Aurora A or Eg5, and leading to cell features of mitotic catastrophe. PPP also increased soluble tubulin and decreased spindle-associated tubulin within minutes, indicating that it interfered with microtubule dynamics. These results provide a novel IGF-1R-independent mechanism of antitumor effects of PPP.

  16. Graviperception in growth inhibition of plant shoots under hypergravity conditions produced by centrifugation is independent of that in gravitropism and may involve mechanoreceptors. (United States)

    Soga, Kouichi; Wakabayashi, Kazuyuki; Kamisaka, Seiichiro; Hoson, Takayuki


    Hypergravity caused by centrifugation inhibits elongation growth of shoots by decreasing the cell wall extensibility via suppression of xyloglucan breakdown as well as by the thickening of cell walls. The mechanism of graviperception in hypergravity-induced growth inhibition was investigated in Arabidopsis [A. thaliana (L.) Heynh.] hypocotyls and azuki bean (Vigna angularis Ohwi et Ohashi) epicotyls. Hypergravity caused growth suppression in both sgr1-1 and pgm1, which are Arabidopsis mutants deprived of gravitropism, as in wild-type plants, suggesting that the graviperception in hypergravity-induced growth inhibition of shoots is independent of that in gravitropism. Hypergravity had no effects on growth of azuki bean epicotyls or Arabidopsis hypocotyls in the presence of lanthanum or gadolinium, which are blockers of mechanoreceptors. Moreover, lanthanum or gadolinium at the same concentration had no influence on gravitropism of azuki bean epicotyls and Arabidopsis hypocotyls. Hypergravity had no effects on cell wall extensibility and affected neither xyloglucan metabolism nor the thickness of cell walls in the lanthanum- or gadolinium-treated azuki bean epicotyls. Lanthanum or gadolinium inhibited the hypergravity-induced increase in the pH of the apoplastic fluid in the epicotyls, which is involved in the processes of the suppression of xyloglucan breakdown due to hypergravity. These findings suggest that plants perceive the hypergravity stimuli by mechanoreceptors in the plasma membrane, and utilize the perceived signal to regulate the growth rate of their shoots.

  17. Experimental study and stress analysis of rock bolt anchorage performance

    Directory of Open Access Journals (Sweden)

    Yu Chen


    Full Text Available A new method was developed to apply pull-and-shear loads to the bolt specimen in order to evaluate the anchorage performance of the rebar bolt and the D-Bolt. In the tests, five displacing angles (0°, 20°, 40°, 60°, and 90°, two joint gaps (0 mm and 30 mm, and three kinds of host rock materials (weak concrete, strong concrete, and concrete-granite were considered, and stress–strain measurements were conducted. Results show that the ultimate loads of both the D-Bolt and the rebar bolt remained constant with any displacing angles. The ultimate displacement of the D-Bolt changed from 140 mm at the 0° displacing angle (pure pull to approximately 70 mm at a displacing angle greater than 40°. The displacement capacity of the D-Bolt is approximately 3.5 times that of the rebar bolt under pure pull and 50% higher than that of the rebar bolt under pure shear. The compressive stress exists at 50 mm from the bolt head, and the maximum bending moment value rises with the increasing displacing angle. The rebar bolt mobilises greater applied load than the D-Bolt when subjected to the maximum bending. The yielding length (at 0° of the D-Bolt is longer than that of the rebar bolt. The displacement capacity of the bolts increased with the joint gap. The bolt subjected to joint gap effect yields more quickly with greater bending moment and smaller applied load. The displacement capacities of the D-Bolt and the rebar bolt are greater in the weak host rock than that in the hard host rock. In pure shear condition, the ultimate load of the bolts slightly decreases in the hard rock. The yielding speed in the hard rock is higher than that in the weak rock.

  18. Quercetin regulates insulin like growth factor signaling and induces intrinsic and extrinsic pathway mediated apoptosis in androgen independent prostate cancer cells (PC-3). (United States)

    Senthilkumar, Kalimuthu; Elumalai, Perumal; Arunkumar, Ramachandran; Banudevi, Sivanantham; Gunadharini, Nandagopal Dharmalingam; Sharmila, Govindaraj; Selvakumar, Kandaswamy; Arunakaran, Jagadeesan


    Progression of prostate cancer is facilitated by growth factors that activate critical signaling cascades thereby promote prostate cancer cell growth, survival, and migration. To investigate the effect of quercetin on insulin-like growth factor signaling and apoptosis in androgen independent prostate cancer cells (PC-3), IGF-IR, PI-3K, p-Akt, Akt, cyclin D1, Bad, cytochrome c, PARP, caspases-9 and 10 protein levels were assessed by western blot analysis. Mitochondrial membrane potency was detected by rhodamine-123 staining. Quercetin induced caspase-3 activity assay was performed for activation of apoptosis. Further, RT-PCR was also performed for Bad, IGF-I, II, IR, and IGFBP-3 mRNA expression. Quercetin significantly increases the proapoptotic mRNA levels of Bad, IGFBP-3 and protein levels of Bad, cytochrome C, cleaved caspase-9, caspase-10, cleaved PARP and caspase-3 activity in PC-3 cells. IGF-IRβ, PI3K, p-Akt, and cyclin D1 protein expression and mRNA levels of IGF-I, II and IGF-IR were decreased significantly. Further, treatment with PI3K inhibitor (LY294002) and quercetin showed decreased p-Akt levels. Apoptosis is confirmed by loss of mitochondrial membrane potential in quercetin treated PC-3 cells. This study suggests that quercetin decreases the survival of androgen independent prostate cancer cells by modulating the expression of insulin-like growth factors (IGF) system components, signaling molecules and induces apoptosis, which could be very useful for the androgen independent prostate cancer treatment.

  19. Nutrient and secondary metabolite concentrations in a savanna are independently affected by large herbivores and shoot growth rate

    CSIR Research Space (South Africa)

    Scogings, PF


    Full Text Available Carbon-based secondary metabolites (CBSMs) such as tannins are assumed to function as plant defences against herbivores. CBSMs are thought to be inversely related to growth rate and nutrient concentrations because a physiological trade-off exists...

  20. C-type natriuretic peptide regulates endochondral bone growth through p38 MAP kinase-dependent and – independent pathways

    Directory of Open Access Journals (Sweden)

    Serra Rosa


    Full Text Available Abstract Background C-type natriuretic peptide (CNP has recently been identified as an important anabolic regulator of endochondral bone growth, but the molecular mechanisms mediating its effects are not completely understood. Results We demonstrate in a tibia organ culture system that pharmacological inhibition of p38 blocks the anabolic effects of CNP. We further show that CNP stimulates endochondral bone growth largely through expansion of the hypertrophic zone of the growth plate, while delaying mineralization. Both effects are reversed by p38 inhibition. We also performed Affymetrix microarray analyses on micro-dissected tibiae to identify CNP target genes. These studies confirmed that hypertrophic chondrocytes are the main targets of CNP signaling in the growth plate, since many more genes were regulated by CNP in this zone than in the others. While CNP receptors are expressed at similar levels in all three zones, cGMP-dependent kinases I and II, important transducers of CNP signaling, are expressed at much higher levels in hypertrophic cells than in other areas of the tibia, providing a potential explanation for the spatial distribution of CNP effects. In addition, our data show that CNP induces the expression of NPR3, a decoy receptor for natriuretic peptides, suggesting the existence of a feedback loop to limit CNP signaling. Finally, detailed analyses of our microarray data showed that CNP regulates numerous genes involved in BMP signaling and cell adhesion. Conclusion Our data identify novel target genes of CNP and demonstrate that the p38 pathway is a novel, essential mediator of CNP effects on endochondral bone growth, with potential implications for understanding and treatment of numerous skeletal diseases.

  1. Evaluation of dredged material proposed for ocean disposal from Liberty Island Anchorage, New York

    Energy Technology Data Exchange (ETDEWEB)

    Pinza, M.R.; Barrows, E.S.; Word, J.Q.


    Sediment samples were collected from the Liberty Island Anchorage and Military Ocean Terminal in Bayonne, New Jersey (MOTBY), during a survey conducted from June 7 through June 10, 1994. Tests and analyses were conducted on Liberty Island Anchorage sediment core samples according to the manual developed by the U.S. Army Corps of Engineers (USACE) and the U.S. Environmental Protection Agency (EPA), Evaluation of Dredged Material Proposed for Ocean Disposal (Testing Manual), and the regional manual developed by the USACE-New York District (NYD) and EPA Region 11, Guidance for Performing Tests on Dredged Material to be Disposed of in Ocean Waters. The evaluation of proposed dredged material from Liberty Island Anchorage consisted of bulk sediment chemical analyses, chemical analyses of site water and elutriate, and water-column and benthic acute toxicity tests. Individual sediment core samples collected from Liberty Island Anchorage were analyzed for grain size, moisture content, and total organic carbon (TOC). A composite sediment sample, representing the entire area proposed for dredging, was analyzed for bulk density, metals, chlorinated pesticides, polychlorinated-biphenyl (PCB) congeners, polynuclear aromatic hydrocarbons (PAH), 1,4-dichlorobenzene, and dioxin/furan congeners. Site water and elutriate water, prepared from the suspended- particulate phase (SPP) of Liberty Island Anchorage sediment, were analyzed for metals, pesticides, and PCBS.

  2. Ankylosed maxillary incisor with severe root resorption treated with a single-tooth dento-osseous osteotomy, vertical alveolar distraction osteogenesis, and mini-implant anchorage. (United States)

    Senışık, Neslihan Ebru; Koçer, Gülperi; Kaya, Bulem Üreyen


    Dentoalveolar ankylosis interferes with the vertical growth of the alveolar process, which can lead to an open bite, an unesthetic smile, and occlusal disharmony. This case report presents a new treatment protocol for an ankylosed tooth with severe root resorption using a combined surgical orthodontic management protocol involving a single-tooth dento-osseous osteotomy and vertical alveolar distraction osteogenesis with intraoral elastics and mini-implant anchorage. After distraction and active orthodontic treatment, the patient's anterior open bite was corrected. A Class I dental relationship was achieved, overjet was decreased, and a normal incisor relationship was obtained.

  3. AtOMA1 Affects the OXPHOS System and Plant Growth in Contrast to Other Newly Identified ATP-Independent Proteases in Arabidopsis Mitochondria. (United States)

    Migdal, Iwona; Skibior-Blaszczyk, Renata; Heidorn-Czarna, Malgorzata; Kolodziejczak, Marta; Garbiec, Arnold; Janska, Hanna


    Compared with yeast, our knowledge on members of the ATP-independent plant mitochondrial proteolytic machinery is rather poor. In the present study, using confocal microscopy and immunoblotting, we proved that homologs of yeast Oma1, Atp23, Imp1, Imp2, and Oct1 proteases are localized in Arabidopsis mitochondria. We characterized these components of the ATP-independent proteolytic system as well as the earlier identified protease, AtICP55, with an emphasis on their significance in plant growth and functionality in the OXPHOS system. A functional complementation assay demonstrated that out of all the analyzed proteases, only AtOMA1 and AtICP55 could substitute for a lack of their yeast counterparts. We did not observe any significant developmental or morphological changes in plants lacking the studied proteases, either under optimal growth conditions or after exposure to stress, with the only exception being retarded root growth in oma1-1, thus implying that the absence of a single mitochondrial ATP-independent protease is not critical for Arabidopsis growth and development. We did not find any evidence indicating a clear functional complementation of the missing protease by any other protease at the transcript or protein level. Studies on the impact of the analyzed proteases on mitochondrial bioenergetic function revealed that out of all the studied mutants, only oma1-1 showed differences in activities and amounts of OXPHOS proteins. Among all the OXPHOS disorders found in oma1-1, the complex V deficiency is distinctive because it is mainly associated with decreased catalytic activity and not correlated with complex abundance, which has been observed in the case of supercomplex I + III2 and complex I deficiencies. Altogether, our study indicates that despite the presence of highly conservative homologs, the mitochondrial ATP-independent proteolytic system is not functionally conserved in plants as compared with yeast. Our findings also highlight the importance of

  4. A phosphatase-independent gain-of-function mutation in PTEN triggers aberrant cell growth in astrocytes through an autocrine IGF-1 loop. (United States)

    Fernández, S; Genis, L; Torres-Alemán, I


    Loss-of-function mutations in the phosphatase PTEN (phosphatase and tensin homolog deleted on chromosome10) contribute to aberrant cell growth in part through upregulation of the mitogenic IGF-1/PI3K/Akt pathway. In turn, this pathway exerts a homeostatic feedback over PTEN. Using mutagenesis analysis to explore a possible impact of this mutual control on astrocyte growth, we found that truncation of the C-terminal region of PTEN (Δ51) associates with a marked increase in NFκB activity, a transcription factor overactivated in astrocyte tumors. Whereas mutations of PTEN are considered to lead to a loss-of-function, PTENΔ51, a truncation that comprises a region frequently mutated in human gliomas, displayed a neomorphic (gain-of-function) activity that was independent of its phosphatase activity. This gain-of-function of PTENΔ51 includes stimulation of IGF-1 synthesis through protein kinase A activation of the IGF-1 promoter. Increased IGF-1 originates an autocrine loop that activates Akt and NFκB. Constitutive activation of NFκB in PTENΔ51-expressing astrocytes leads to aberrant cell growth; astrocytes expressing this mutant PTEN generate colonies in vitro and tumors in vivo. Mutations converting a tumor suppressor such as PTEN into a tumor promoter through a gain-of-function involving IGF-1 production may further our understanding of the role played by this growth factor in glioma growth and help us define druggable targets for personalized therapy.

  5. Maternal factors associated with fetal growth and birthweight are independent determinants of placental weight and exhibit differential effects by fetal sex.

    Directory of Open Access Journals (Sweden)

    Marie Cecilie Paasche Roland

    Full Text Available INTRODUCTION: Maternal nutritional and metabolic factors influence the developmental environment of the fetus. Virtually any nutritional factor in the maternal blood has to pass the placental membranes to reach the fetal blood. Placental weight is a commonly used measure to summarize placental growth and function. Placental weight is an independent determinant of fetal growth and birthweight and modifies the associations between maternal metabolic factors and fetal growth. We hypothesized that maternal factors known to be related to fetal growth, newborn size and body composition are determinants of placental weight and that effects of maternal metabolic factors on placental weight differ between the genders. METHODS: The STORK study is a prospective longitudinal study including 1031 healthy pregnant women of Scandinavian heritage with singleton pregnancies. Maternal determinants (parity, body mass index, gestational weight gain and fasting plasma glucose of placental weight were explored by linear regression models, stratified by fetal sex. RESULTS: Parity, maternal BMI, gestational weight gain and fasting glucose had positive effects on placental weight. There was a sex specific effect in these associations. Fasting glucose was significantly associated with placental weight in females but not in males. CONCLUSION: Maternal factors known to influence fetal growth, birthweight and neonatal body composition are determinants of placental weight. The effect of maternal factors on placental weight is influenced by sex as illustrated in the relation between maternal glucose and placental weight.

  6. Inhibition of Androgen-Independent Growth of Prostate Cancer by siRNA- Mediated Androgen Receptor Gene Silencing (United States)


    Center, Kansas City, KS 66160, USA Introduction Prostate cancer is the most common cancer diagnosed after skin cancers and the... cancer cell growth: androgen regulation of CDK2, CDK4 , and CKI p16 genes. Cancer Res. 1997; 57:4511-4516. 109. Gregory CW, Hamil KG, Kim D, Hall SH...the most diagnosed non- skin cancer and the second leading cause of cancer -related death [2]. Currently, prostate-specific antigen (PSA) is the most

  7. Receptor-dependent and receptor-independent endocannabinoid signaling: a therapeutic target for regulation of cancer growth. (United States)

    Van Dross, Rukiyah; Soliman, Eman; Jha, Shalini; Johnson, Travious; Mukhopadhyay, Somnath


    The endocannabinoid system comprises the G-protein coupled CB1 cannabinoid receptor (CB1R) and CB2 cannabinoid receptor (CB2R), their endogenous ligands (endocannabinoids), and the enzymes responsible for their synthesis and catabolism. Recent works have revealed several important interactions between the endocannabinoid system and cancer. Moreover, it is now well established that synthetic small molecule cannabinoid receptor agonist acting on either CB1R or CB2R or both exerts anti-cancer effects on a variety of tumor cells. Recent results from many laboratories reported that the expression of CB1R and CB2R in prostate cancer, breast cancer, and many other cancer cells is higher than that in corresponding non-malignant tissues. The mechanisms by which cannabinoids acting on CB1R or CB2R exert their effects on cancer cells are quite diverse and complex. Further, several studies demonstrated that some of the anti-proliferative and apoptotic effects of cannabinoids are mediated by receptor-independent mechanisms. In this minireview we provide an overview of the major findings on the effects of endogenous and/or synthetic cannabinoids on breast and prostate cancers. We also provide insight into receptor independent mechanisms of the anti-cancer effects of cannabinoids under in vitro and in vivo conditions. Copyright © 2012 Elsevier Inc. All rights reserved.

  8. Feasibility Verification of Mountable PZT-Interface for Impedance Monitoring in Tendon-Anchorage

    Directory of Open Access Journals (Sweden)

    Thanh-Canh Huynh


    Full Text Available This study has been motivated to numerically evaluate the performance of the mountable PZT-interface for impedance monitoring in tendon-anchorage. Firstly, electromechanical impedance monitoring and feature classification methods are outlined. Secondly, a structural model of tendon-anchorage subsystem with mountable PZT-interface is designed for impedance monitoring. Finally, the feasibility of the mountable PZT-interface is numerically examined. A finite element (FE model is designed for the lab-scaled tendon-anchorage. The FE model of the PZT-interface is tuned as its impedance signatures meet the experimental test results at the same frequency ranges and also with identical patterns. Equivalent model properties of the FE model corresponding to prestress forces inflicted on the lab-tested structure are identified from the fine-tuning practice.

  9. Skeletal anchorage in orthodontics--a review of various systems in animal and human studies. (United States)

    Janssen, Krista I; Raghoebar, Gerry M; Vissink, Arjan; Sandham, Andrew


    The aim of the present investigation was to review and evaluate the current literature on skeletal bone anchorage in orthodontics with regard to success rates of the various systems. MEDLINE, PubMed, and Cochrane searches (period January 1966 to January 2006, English language) of animal and human studies using skeletal anchorage during orthodontic treatment were scrutinized. A total of 50 relevant articles were identified which investigated various types of implants. Two types of anchorage systems are used in orthodontics: (1) osseointegrated dental implants, including temporary mid-palatal implants. These systems were associated with a wide variety of success rates in animal studies. In human studies, the systems were shown to be reliable, with success rates between 85% and 100% (ie, systems still functioning at the end of the orthodontic treatment). (2) Nonosseointegrated mini-plates and mini-screw anchorage systems. Titanium miniplates were associated with 100% success in animals, and hardly any loss of these mini-plates (bone anchors) were lost due to infection in human studies, with success rates between 91% and 100%. Few long-term studies on nonosseointegrated mini-screws were found, but in animal studies, success rates ranged from 90% to 100%. A success rate of more than 75% in human studies is considered favorable for these orthodontic implants, which confirms the clinical applicability of this type of immediate loading anchor support in orthodontics. Both animal and human studies revealed that mesiodistal and intrusion movements can be reliably carried out by means of skeletal anchorage devices. A drawback is that animal studies do not reflect the real orthodontic clinical situation; thus, the outcome of these studies should be interpreted with caution. Human studies, however, show that orthodontic forces between 100 and 400 grams can be applied successfully to skeletal anchorage devices. Appropriate treatment strategies need to be confirmed by randomized

  10. Export of the HR eliciting protein, Harpin(Es), of the maize pathogen Erwinia stewartii is species-specific but is independent of the growth temperature. (United States)

    Ahmad, Musharaf; Alam, Syed Sartaj; Alam, Shah; Usman, Amjad; Coplin, David L


    The extra-cellular export of the HR-eliciting protein, Harpin(Es) of the maize pathogen Erwinia stewartii was studied to find out if the protein needs any species-specific signal for its export and to determine if the export of the protein to the medium is affected in any way by the growth temperature. Based upon the experimental evidence, it was proved that the protein (i.e., Harpin(Es)) does require its own export system (species-specific) to get out of the bacterial cell and can not be exported by the export system of even the very closely related bacterium, Erwinia amylovora. It was also found that the export of Harpin(Es) is, unlike the case of Harpin(Ea) (HR-eliciting protein of Erwinia amylovora), independent of the growth temperature.

  11. Differences of treatment outcomes between self-ligating brackets with microimplant and headgear anchorages in adults with bimaxillary protrusion. (United States)

    Chen, Mu; Li, Zheng-Ming; Liu, Xue; Cai, Bin; Wang, Da-Wei; Feng, Zhi-Cai


    Our aim was to determine differences between the outcomes of treatment using microimplant anchorage compared with headgear anchorage in adult patients with bimaxillary protrusion treated with self-ligating brackets. Thirty-one adult orthodontic patients (13 men, 18 women; age, 25.87 ± 3.37 years) who were diagnosed with bimaxillary protrusion were selected. All patients were treated with self-ligating brackets and maximum anchorage after extraction of 4 first premolars. Group 1 received microimplant anchorage, and group 2 received headgear. Lateral cephalometric radiographs were obtained before and after treatment. Differences in the skeletal and dental parameters between and within groups were analyzed. No significant difference was observed in the mean treatment times between the groups (21.93 ± 3.10 vs 23.88 ± 2.68 months). There was no significant difference in skeletal measurements before or after treatment in patients who received microimplant anchorage. Patients who received headgear anchorage had an increase of the mandibular plane angle. The microimplant anchorage group had greater anterior tooth retraction and less maxillary molar mesialization than did the headgear group. In both the anteroposterior and vertical directions, microimplant anchorage achieved better control than did the traditional headgear appliance during the treatment of bimaxillary protrusion. Copyright © 2015 American Association of Orthodontists. Published by Elsevier Inc. All rights reserved.

  12. Growth hormone (GH)-independent dimerization of GH receptor by a leucine zipper results in constitutive activation

    DEFF Research Database (Denmark)

    Behncken, S N; Billestrup, Nils; Brown, R;


    Growth hormone initiates signaling by inducing homodimerization of two GH receptors. Here, we have sought to determine whether constitutively active receptor can be created in the absence of the extracellular domain by substituting it with high affinity leucine zippers to create dimers of the gro......Growth hormone initiates signaling by inducing homodimerization of two GH receptors. Here, we have sought to determine whether constitutively active receptor can be created in the absence of the extracellular domain by substituting it with high affinity leucine zippers to create dimers...... proliferation after interleukin 3 withdrawal at a rate equal to maximally stimulated wild type GHR-expressing cells. Activation of STAT 5b was also observed in Fos-Jun-GHR-expressing cells at a level equal to that in chronically GH-treated GHR-expressing cells. Thus, forced dimerization of the transmembrane...... and cytoplasmic domains of the GHR in the absence of the extracellular domain can lead to the constitutive activation of known GH signaling end points, supporting the view that proximity of Janus kinase 2 (JAK2) kinases is the essential element in signaling. Such constitutively active GH receptors may have...

  13. Bio-cultural anchorage of the prickly pear cactus in Tlalnepantla (Morelos), Mexico


    Torres-Salcido, Gerardo; Ramos-Chávez, Alejandro; Urreta-Fernández, Álvaro


    The prickly pear cactus is a source of food with strong bio-cultural anchorage in Mexico. This is due to at least three factors: 1) the nature and heritage of cacti; 2) cultural heritage; and 3) the socio-cultural relationships with historical and symbolic roots that have facilitated knowledge of how to cultivate it and how to use it. The aim of this article is to put factors of territorial anchorage and its historical transformation in context by examining the case of the municipality of Tla...

  14. The rice REDUCED CULM NUMBER11 gene controls vegetative growth under low-temperature conditions in paddy fields independent of RCN1/OsABCG5. (United States)

    Funabiki, Atsushi; Takano, Sho; Matsuda, Shuichi; Tokuji, Yoshihiko; Takamure, Itsuro; Kato, Kiyoaki


    Low temperature tolerance during vegetative growth is an important objective in rice (Oryza sativa L.) breeding programs. We isolated a novel reduced culm number mutant, designated reduced culm number11 (rcn11), by screening under low-temperature condition in a paddy fields. Since the shoot architecture of the rcn11 was very similar to that of the rcn1, we examined whether RCN11 is involved in RCN1/OsABCG5-associated vegetative growth control. The rcn11 mutant has no mutation in the RCN1/OsABCG5 gene and rcn11 has no effect on RCN1/OsABCG5 gene expression. In the rcn1 mutant, RCN1/OsABCG5 was upregulated showing that RCN1/OsABCG5 is controlled by negative feedback regulation. Absence of an effect of rcn11 on RCN1/OsABCG5 feedback regulation supported that RCN11 is not involved in the RCN1/OsABCG5-associated transport system. A genetic allelism test and molecular mapping study showed that rcn11 is independent of rcn1 on rice chromosome 3 and located on chromosome 8. The rcn1 rcn11 phenotype suggests that RCN11 acts on vegetative growth independent of RCN1/OsABCG5. A root development comparison between rcn1 and rcn11 in young seedlings represented that rcn11 reduced crown root number and elongation, whereas rcn1 reduced lateral root density and elongation. Thus, rcn11 will shed new light on vegetative growth control under low temperature.

  15. Loss of androgen receptor-dependent growth suppression by prostate cancer cells can occur independently from acquiring oncogenic addiction to androgen receptor signaling.

    Directory of Open Access Journals (Sweden)

    Jason M D'Antonio

    Full Text Available The conversion of androgen receptor (AR signaling as a mechanism of growth suppression of normal prostate epithelial cells to that of growth stimulation in prostate cancer cells is often associated with AR mutation, amplification and over-expression. Thus, down-regulation of AR signaling is commonly therapeutic for prostate cancer. The E006AA cell line was established from a hormone naïve, localized prostate cancer. E006AA cells are genetically aneuploid and grow equally well when xenografted into either intact or castrated male NOG but not nude mice. These cells exhibit: 1 X chromosome duplication and AR gene amplification, although paradoxically not coupled with increased AR expression, and 2 somatic, dominant-negative Serine-599-Glycine loss-of-function mutation within the dimerization surface of the DNA binding domain of the AR gene. No effect on the growth of E006AA cells is observed using targeted knockdown of endogenous mutant AR, ectopic expression of wild-type AR, or treatment with androgens or anti-androgens. E006AA cells represent a prototype for a newly identified subtype of prostate cancer cells that exhibit a dominant-negative AR loss-of-function in a hormonally naïve patient. Such loss-of-function eliminates AR-mediated growth suppression normally induced by normal physiological levels of androgens, thus producing a selective growth advantage for these malignant cells in hormonally naïve patients. These data highlight that loss of AR-mediated growth suppression is an independent process, and that, without additional changes, is insufficient for acquiring oncogene addiction to AR signaling. Thus, patients with prostate cancer cells harboring such AR loss-of-function mutations will not benefit from aggressive hormone or anti-AR therapies even though they express AR protein.

  16. Phellinus linteus suppresses growth, angiogenesis and invasive behaviour of breast cancer cells through the inhibition of AKT signalling. (United States)

    Sliva, D; Jedinak, A; Kawasaki, J; Harvey, K; Slivova, V


    The antitumour activity of a medicinal mushroom Phellinus linteus (PL), through the stimulation of immune system or the induction of apoptosis, has been recently described. However, the molecular mechanisms responsible for the inhibition of invasive behaviour of cancer cells remain to be addressed. In the present study, we demonstrate that PL inhibits proliferation (anchorage-dependent growth) as well as colony formation (anchorage-independent growth) of highly invasive human breast cancer cells. The growth inhibition of MDA-MB-231 cells is mediated by the cell cycle arrest at S phase through the upregulation of p27(Kip1) expression. Phellinus linteus also suppressed invasive behaviour of MDA-MB-231 cells by the inhibition of cell adhesion, cell migration and cell invasion through the suppression of secretion of urokinase-plasminogen activator from breast cancer cells. In addition, PL markedly inhibited the early event in angiogenesis, capillary morphogenesis of the human aortic endothelial cells, through the downregulation of secretion of vascular endothelial growth factor from MDA-MB-231 cells. These effects are mediated by the inhibition of serine-threonine kinase AKT signalling, because PL suppressed phosphorylation of AKT at Thr(308) and Ser(473) in breast cancer cells. Taken together, our study suggests potential therapeutic effect of PL against invasive breast cancer.

  17. TL1A induces TCR independent IL-6 and TNF-α production and growth of PLZF+ leukocytes

    DEFF Research Database (Denmark)

    Reichwald, Kirsten; Jørgensen, Tina Z.; Tougaard, Peter


    An elevated level of the cytokine TL1A is known to be associated with several autoimmune diseases, e.g. rheumatoid arthritis and inflammatory bowel disease. However, the mode of action of TL1A remains elusive. In this study, we investigated the role of TL1A in a pro-inflammatory setting, using...... human leukocytes purified from healthy donors. We show that TL1A, together with IL-12, IL-15 and IL-18, directly induces the production of IL-6 and TNF-α from leukocytes. Interestingly, TL1A-induced IL-6 was not produced by CD14(+) monocytes. We further show that the produced IL-6 is fully functional......, as measured by its ability to signal through the IL-6 receptor, and that the induction of IL-6 is independent of TCR stimulation. Furthermore, the transcription factor PLZF was induced in stimulated cells. These results offer a substantial explanation for the role of TL1A, since TNF-α and IL-6 are directly...

  18. Activity of Bdellovibrio hit locus proteins, Bd0108 and Bd0109, links Type IVa pilus extrusion/retraction status to prey-independent growth signalling.

    Directory of Open Access Journals (Sweden)

    Michael J Capeness

    Full Text Available Bdellovibrio bacteriovorus are facultatively predatory bacteria that grow within gram-negative prey, using pili to invade their periplasmic niche. They also grow prey-independently on organic nutrients after undergoing a reversible switch. The nature of the growth switching mechanism has been elusive, but several independent reports suggested mutations in the hit (host-interaction locus on the Bdellovibrio genome were associated with the transition to prey-independent growth. Pili are essential for prey entry by Bdellovibrio and sequence analysis of the hit locus predicted that it was part of a cluster of Type IVb pilus-associated genes, containing bd0108 and bd0109. In this study we have deleted the whole bd0108 gene, which is unique to Bdellovibrio, and compared its phenotype to strains containing spontaneous mutations in bd0108 and the common natural 42 bp deletion variant of bd0108. We find that deletion of the whole bd0108 gene greatly reduced the extrusion of pili, whereas the 42 bp deletion caused greater pilus extrusion than wild-type. The pili isolated from these strains were comprised of the Type IVa pilin protein; PilA. Attempts to similarly delete gene bd0109, which like bd0108 encodes a periplasmic/secreted protein, were not successful, suggesting that it is likely to be essential for Bdellovibrio viability in any growth mode. Bd0109 has a sugar binding YD- repeat motif and an N-terminus with a putative pilin-like fold and was found to interact directly with Bd0108. These results lead us to propose that the Bd0109/Bd0108 interaction regulates pilus production in Bdellovibrio (possibly by interaction with the pilus fibre at the cell wall, and that the presence (and possibly retraction state of the pilus feeds back to alter the growth state of the Bdellovibrio cell. We further identify a novel small RNA encoded by the hit locus, the transcription of which is altered in different bd0108 mutation backgrounds.

  19. Radiation Induced Apoptosis of Murine Bone Marrow Cells Is Independent of Early Growth Response 1 (EGR1) (United States)

    Oben, Karine Z.; Gachuki, Beth W.; Alhakeem, Sara S.; McKenna, Mary K.; Liang, Ying; St. Clair, Daret K.; Rangnekar, Vivek M.; Bondada, Subbarao


    An understanding of how each individual 5q chromosome critical deleted region (CDR) gene contributes to malignant transformation would foster the development of much needed targeted therapies for the treatment of therapy related myeloid neoplasms (t-MNs). Early Growth Response 1 (EGR1) is a key transcriptional regulator of myeloid differentiation located within the 5q chromosome CDR that has been shown to regulate HSC (hematopoietic stem cell) quiescence as well as the master regulator of apoptosis—p53. Since resistance to apoptosis is a hallmark of malignant transformation, we investigated the role of EGR1 in apoptosis of bone marrow cells; a cell population from which myeloid malignancies arise. We evaluated radiation induced apoptosis of Egr1+/+ and Egr1-/- bone marrow cells in vitro and in vivo. EGR1 is not required for radiation induced apoptosis of murine bone marrow cells. Neither p53 mRNA (messenger RNA) nor protein expression is regulated by EGR1 in these cells. Radiation induced apoptosis of bone marrow cells by double strand DNA breaks induced p53 activation. These results suggest EGR1 dependent signaling mechanisms do not contribute to aberrant apoptosis of malignant cells in myeloid malignancies. PMID:28081176

  20. Cytokine-independent growth and clonal expansion of a primary human CD8+ T-cell clone following retroviral transduction with the IL-15 gene. (United States)

    Hsu, Cary; Jones, Stephanie A; Cohen, Cyrille J; Zheng, Zhili; Kerstann, Keith; Zhou, Juhua; Robbins, Paul F; Peng, Peter D; Shen, Xinglei; Gomes, Theotonius J; Dunbar, Cynthia E; Munroe, David J; Stewart, Claudia; Cornetta, Kenneth; Wangsa, Danny; Ried, Thomas; Rosenberg, Steven A; Morgan, Richard A


    Malignancies arising from retrovirally transduced hematopoietic stem cells have been reported in animal models and human gene therapy trials. Whether mature lymphocytes are susceptible to insertional mutagenesis is unknown. We have characterized a primary human CD8(+) T-cell clone, which exhibited logarithmic ex vivo growth in the absence of exogenous cytokine support for more than 1 year after transduction with a murine leukemia virus-based vector encoding the T-cell growth factor IL-15. Phenotypically, the clone was CD28(-), CD45RA(-), CD45RO(+), and CD62L(-), a profile consistent with effector memory T lymphocytes. After gene transfer with tumor-antigen-specific T-cell receptors, the clone secreted IFN-gamma upon encountering tumor targets, providing further evidence that they derived from mature lymphocytes. Gene-expression analyses revealed no evidence of insertional activation of genes flanking the retroviral insertion sites. The clone exhibited constitutive telomerase activity, and the presence of autocrine loop was suggested by impaired cell proliferation following knockdown of IL-15R alpha expression. The generation of this cell line suggests that nonphysiologic expression of IL-15 can result in the long-term in vitro growth of mature human T lymphocytes. The cytokine-independent growth of this line was a rare event that has not been observed in other IL-15 vector transduction experiments or with any other integrating vector system. It does not appear that the retroviral vector integration sites played a role in the continuous growth of this cell clone, but this remains under investigation.

  1. 78 FR 51061 - Special Anchorage Areas; Port of New York, NY (United States)


    ... convenient access to public transportation, onshore shopping and amenities which facilitate interstate and... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HOMELAND SECURITY Coast Guard 33 CFR Part 110 RIN 1625-AA01 Special Anchorage Areas; Port of New York, NY AGENCY...

  2. Three-dimensional finite element analysis of a newly designed onplant miniplate anchorage system. (United States)

    Liu, Lin; Qu, Yin-Ying; Jiang, Li-Jun; Zhou, Qian; Tang, Tian-Qi


    The purpose of this research was to evaluate the structural stress and deformation of a newly designed onplant miniplate anchorage system compared to a standard anchorage system. A bone block integrated with a novel miniplate and fixation screw system was simulated in a three-dimensional model and subjected to force at different directions. The stress distribution and deformation of the miniplate system and cortical bone were evaluated using the three-dimensional finite element method. The results showed that the stress on the plate system and bone was linearly proportional to the force magnitude and was higher when the force was in a vertical direction (Y-axis). Stress and deformation values of the two screws (screw 1 and 2) were asymmetric when the force was added along Y-axis and was greater in screw 1. The highest deformation value of the screws was 7.5148 μm, much smaller than the limit value. The load was decreased for each single miniscrew, and the ability of the new anchorage system to bear the load was also enhanced to some degree. It was suggested that the newly designed onplant miniplate anchorage system is effective, easily implanted and minimally invasive.

  3. Oxidative Stress Modulates DNA Methylation during Melanocyte Anchorage Blockade Associated with Malignant Transformation

    Directory of Open Access Journals (Sweden)

    Ana C.E. Campos


    Full Text Available Both oxidative/nitrosative stress and alterations in DNA methylation are observed during carcinogenesis of different tumor types, but no clear correlation between these events has been demonstrated until now. Melanoma cell lines were previously established after submitting the nontumorigenic melanocyte lineage, melan-a, to cycles of anchorage blockade. In this work, increased intracellular oxidative species and nitric oxide levels, as well as alterations in the DNA methylation, were observed after melan-a detachment, which were also associated with a decrease in intracellular homocysteine (Hey, an element in the methionine (universal methyl donor cycle. This alteration was accompanied by increase in glutathione (GSH levels and methylated DNA content. Furthermore, a significant increase in dnmti and 3b expression was identified along melan-a anchorage blockade. LG-Nitro-L-arginine methyl esther (L-NAME, known as a nitric oxide synthase (NOS inhibitor, and N-acetyl-L-cysteine (NAC prevented the increase in global DNA methylation, as well as the increase in dnmti and 3b expression, observed during melan-a detachment. Interestingly, both L-NAME and NAC did not inhibit nitric oxide (NO production in these cells, but abrogated superoxide anion production during anchorage blockade. In conclusion, oxidative stress observed during melanocyte anchorage blockade seems to modulate DNA methylation levels and may directly contribute to the acquisition of an anoikis-resistant phenotype through an epigenetic mechanism.

  4. Extraction treatment of an adult patient with severe bimaxillary dentoalveolar protrusion using microscrew anchorage

    Institute of Scientific and Technical Information of China (English)

    OUYANG Li; ZHOU Yan-heng; FU Min-kui; DING Peng


    @@ Bimaxillary dentoalveolar protrusion is one of the most prevalent malocclusion in Asian population,1 Traditionally, orthodontic treatment often involves the extraction of four first premolars2 and demands the least amount of anchorage loss, therefore headgear used to be an unavoid- able fate of these patients.

  5. 33 CFR 110.220 - Pacific Ocean at San Nicolas Island, Calif.; restricted anchorage areas. (United States)


    ... Pacific Ocean at San Nicolas Island, Calif.; restricted anchorage areas. (a) The restricted areas—(1) East area. All waters within a circle having a radius of one nautical mile centered at latitude 33°13′45... approximately 101°, 420 yards, from San Nicolas Island East End Light. (2) West area. Shoreward of a...

  6. Thick-Walled Cylinder Theory Applied on a Conical Wedge Anchorage

    DEFF Research Database (Denmark)

    Bennitz, Anders; Grip, Niklas; Schmidt, Jacob Wittrup


    Conical wedge anchorages are frequently used to anchor steel tendons in prestressing applications within the construction industry. To replace the steel tendons with non-corrosive and low weight FRPs (Fiber Reinforced Polymers), the different mechanical interactions between the steel and FRPs call...

  7. Biofilm formation on surface characterized micro-implants for skeletal anchorage in orthodontics

    NARCIS (Netherlands)

    Chin, Yeen; Sandham, John; de Vries, Jacob; van der Mei, Henderina; Busscher, Hendrik

    Micro-implants are increasingly popular in clinical orthodontics to effect skeletal anchorage. However, biofilm formation on their surfaces and subsequent infection of peri-implant tissues can result in either exfoliation or surgical removal of these devices. The present study aimed to assess

  8. 75 FR 23804 - Notice of Inventory Completion: Alaska State Office, Bureau of Land Management, Anchorage, AK... (United States)


    ... National Park Service Notice of Inventory Completion: Alaska State Office, Bureau of Land Management... completion of an inventory of human remains and associated funerary objects in the control of the U.S. Department of the Interior, Bureau of Land Management, Alaska State Office, Anchorage, AK, and in...

  9. 76 FR 80394 - Notice of Inventory Completion: Alaska State Office, Bureau of Land Management, Anchorage, AK (United States)


    ... Inventory Completion: Alaska State Office, Bureau of Land Management, Anchorage, AK AGENCY: National Park Service, Interior. ACTION: Notice. SUMMARY: The Alaska State Office, Bureau of Land Management has... completion of an inventory of human remains in the control of the Bureau of Land Management (BLM) that...

  10. 77 FR 35104 - Notice of Request To Release Airport Property at Merrill Field Airport, Anchorage, AK (United States)


    ... Anchorage, Alaska, on June 6, 2012. Byron K. Huffman, Division Manager, FAA, Alaskan Region. BILLING CODE... lands in accordance with Title 23, Part 710.509 of the Code of Federal Regulations and Section 6.13 of...-26, ARD. In accordance with Title 49 of the United States Code (U.S.C.), Section 47107(h)(2),...

  11. Biofilm formation on surface characterized micro-implants for skeletal anchorage in orthodontics

    NARCIS (Netherlands)

    Chin, Yeen; Sandham, John; de Vries, Jacob; van der Mei, Henderina; Busscher, Hendrik


    Micro-implants are increasingly popular in clinical orthodontics to effect skeletal anchorage. However, biofilm formation on their surfaces and subsequent infection of peri-implant tissues can result in either exfoliation or surgical removal of these devices. The present study aimed to assess biofil

  12. Root resorption of maxillary incisors retracted with and without skeletal anchorage. (United States)

    Barros, Sérgio Estelita; Janson, Guilherme; Chiqueto, Kelly; Baldo, Vitor Oliveira; Baldo, Taiana Oliveira


    Our objective was to compare root resorption degree of the maxillary central incisors retracted with and without skeletal anchorage. This nonrandomized historical control study included 37 patients requiring maximum anterior retraction and treated with extraction of 2 maxillary premolars. Group 1 consisted of 22 patients (11 male, 11 female) in whom anterior retraction was performed without skeletal anchorage, and group 2 included 15 patients (3 male, 12 female) treated with skeletally anchored anterior retraction. Periapical radiographs were used to evaluate root resorption degree by a scoring system. The groups were compared regarding the resorption score and resorption degree distribution with the Mann-Whitney U test, chi-square test, and Z test on proportions. There was no statistically significant intergroup difference regarding root resorption, but the number of patients with severe and extreme root resorption degrees was significantly greater in group 2. Although the root resorption degree of the skeletal anchorage group was not significantly different from the group without skeletal anchorage, the number of patients with severe to extreme resorption in the first group was significantly greater. Therefore, careful clinical monitoring of skeletally anchored anterior retraction is needed, especially when there are known root resorption predisposing factors. Copyright © 2017 American Association of Orthodontists. Published by Elsevier Inc. All rights reserved.

  13. Skeletal anchorage in orthodontics : A review of various systems in animal and human studies

    NARCIS (Netherlands)

    Janssen, Krista I.; Raghoebar, Gerry M.; Vissink, Arjan; Sandham, John


    Purpose: The aim of the present investigation was to review and evaluate the current literature on skeletal bone anchorage in orthodontics with regard to success rates of the various systems. Materials and Methods: MEDLINE, PubMed, and Cochrane searches (period January 1966 to January 2006, English

  14. Determinants for success rates of temporary anchorage devices in orthodontics: a meta-analysis (n > 50). (United States)

    Dalessandri, Domenico; Salgarello, Stefano; Dalessandri, Michela; Lazzaroni, Elena; Piancino, Mariagrazia; Paganelli, Corrado; Maiorana, Carlo; Santoro, Franco


    The aim of this study was to review the literature and evaluate the failure rates and factors that affect the stability and success of temporary anchorage devices (TADs) used as orthodontic anchorage. Data were collected from electronic databases: MEDLINE database, Scopus, and Web of Knowledge. Four combinations of term were used as keywords: screw orthodontic failure, screw orthodontic success, implant orthodontic failure, and implant orthodontic success. The following selection criteria were used to select appropriate articles: articles on implants and screws used as orthodontic anchorage, data only from human subjects, studies published in English, studies with more than 50 implants/screws, and both prospective and retrospective clinical studies. The search provided 209 abstracts about TADs used as anchorage. After reading and applying the selection criteria, 26 articles were included in the study. The data obtained were divided into two topics: which factors affected TAD success and to what degree and in how many articles they were quoted. Clinical factors were divided into three main groups: patient-related, implant-related, and management-related factors. Although all articles included in this meta-analysis reported success rates of greater than 80 per cent, the factors determining success rates were inconsistent between the studies analysed and this made conclusions difficult.

  15. Are orthodontic distalizers reinforced with the temporary skeletal anchorage devices effective?

    NARCIS (Netherlands)

    Fudalej, P.S.; Antoszewska, J.


    INTRODUCTION: Our objective was to perform a systematic review of studies pertaining to the distalization of teeth with appliances reinforced with temporary skeletal anchorage devices. METHODS: PubMed, Embase, Cochrane Central Register of Controlled Trials, Web of Knowledge, Ovid, and Scopus were se

  16. Evaluating School Wellness Policy in Curbing Childhood Obesity in Anchorage, Alaska (United States)

    Parsons, Wendy G.; Garcia, Gabriel M.; Hoffman, Pamela K.


    In 2006, the Anchorage School District implemented a school wellness policy to address the problem of obesity among its elementary-aged students. We assessed whether the addition of this policy is effective in protecting or preventing students from becoming overweight/obese over time. The methods involved following two cohorts of students for 5…

  17. The heparan sulfate co-receptor and the concentration of fibroblast growth factor-2 independently elicit different signalling patterns from the fibroblast growth factor receptor

    Directory of Open Access Journals (Sweden)

    Duchesne Laurence


    Full Text Available Abstract Background The fibroblast growth factor receptor (FGFR interprets concentration gradients of FGF ligands and structural changes in the heparan sulfate (HS co-receptor to generate different cellular responses. However, whether the FGFR generates different signals is not known. Results We have previously shown in rat mammary fibroblasts that in cells deficient in sulfation, and so in HS co-receptor, FGF-2 can only stimulate a transient phosphorylation of p42/44 MAPK and so cannot stimulate DNA synthesis. Here we demonstrate that this is because in the absence of HS, FGF-2 fails to stimulate the phosphorylation of the adaptor FGFR substrate 2 (FRS2. In cells possessing the HS co-receptor, FGF-2 elicits a bell-shaped dose response: optimal concentrations stimulate DNA synthesis, but supramaximal concentrations (≥ 100 ng/mL have little effect. At optimal concentrations (300 pg/mL FGF-2 stimulates a sustained dual phosphorylation of p42/44 MAPK and tyrosine phosphorylation of FRS2. In contrast, 100 ng/mL FGF-2 only stimulates a transient early peak of p42/44 MAPK phosphorylation and fails to stimulate appreciably the phosphorylation of FRS2 on tyrosine. Conclusions These results suggest that the nature of the FGFR signal produced is determined by a combination of the HS co-receptor and the concentration of FGF ligand. Both the phosphorylation of the adaptor FRS2, the kinetics (sustained or transient of phosphorylation of p42/44(MAPK are varied, and so differing cellular responses are produced.

  18. A role for Mfb1p in region-specific anchorage of high-functioning mitochondria and lifespan in Saccharomyces cerevisiae. (United States)

    Pernice, Wolfgang M; Vevea, Jason D; Pon, Liza A


    Previous studies indicate that replicative lifespan in daughter cells of Sacchraromyces cerevisiae depends on the preferential inheritance of young, high-functioning mitochondria. We report here that mitochondria are functionally segregated even within single mother cells in S. cerevisiae. A high-functioning population of mitochondria accumulates at the tip of the mother cell distal to the bud. We find that the mitochondrial F-box protein (Mfb1p) localizes to mitochondria in the mother tip and is required for mitochondrial anchorage at that site, independent of the previously identified anchorage protein Num1p. Deletion of MFB1 results in loss of the mother-tip-localized mitochondrial population, defects in mitochondrial function and premature replicative ageing. Inhibiting mitochondrial inheritance to buds, by deletion of MMR1, in mfb1Δ cells restores mitochondrial distribution, promotes mitochondrial function and extends replicative lifespan. Our results identify a mechanism that retains a reservoir of high-functioning mitochondria in mother cells and thereby preserves maternal reproductive capacity.

  19. Betulinic acid inhibits colon cancer cell and tumor growth and induces proteasome-dependent and -independent downregulation of specificity proteins (Sp transcription factors

    Directory of Open Access Journals (Sweden)

    Pathi Satya


    Full Text Available Abstract Background Betulinic acid (BA inhibits growth of several cancer cell lines and tumors and the effects of BA have been attributed to its mitochondriotoxicity and inhibition of multiple pro-oncogenic factors. Previous studies show that BA induces proteasome-dependent degradation of specificity protein (Sp transcription factors Sp1, Sp3 and Sp4 in prostate cancer cells and this study focused on the mechanism of action of BA in colon cancer cells. Methods The effects of BA on colon cancer cell proliferation and apoptosis and tumor growth in vivo were determined using standardized assays. The effects of BA on Sp proteins and Sp-regulated gene products were analyzed by western blots, and real time PCR was used to determine microRNA-27a (miR-27a and ZBTB10 mRNA expression. Results BA inhibited growth and induced apoptosis in RKO and SW480 colon cancer cells and inhibited tumor growth in athymic nude mice bearing RKO cells as xenograft. BA also decreased expression of Sp1, Sp3 and Sp4 transcription factors which are overexpressed in colon cancer cells and decreased levels of several Sp-regulated genes including survivin, vascular endothelial growth factor, p65 sub-unit of NFκB, epidermal growth factor receptor, cyclin D1, and pituitary tumor transforming gene-1. The mechanism of action of BA was dependent on cell context, since BA induced proteasome-dependent and proteasome-independent downregulation of Sp1, Sp3 and Sp4 in SW480 and RKO cells, respectively. In RKO cells, the mechanism of BA-induced repression of Sp1, Sp3 and Sp4 was due to induction of reactive oxygen species (ROS, ROS-mediated repression of microRNA-27a, and induction of the Sp repressor gene ZBTB10. Conclusions These results suggest that the anticancer activity of BA in colon cancer cells is due, in part, to downregulation of Sp1, Sp3 and Sp4 transcription factors; however, the mechanism of this response is cell context-dependent.

  20. Deficiency in the 15 kDa Selenoprotein Inhibits Human Colon Cancer Cell Growth

    Directory of Open Access Journals (Sweden)

    Ryuta Tobe


    Full Text Available Selenium is an essential micronutrient for humans and animals, and is thought to provide protection against some forms of cancer. These protective effects appear to be mediated, at least in part, through selenium-containing proteins (selenoproteins. Recent studies in a mouse colon cancer cell line have shown that the 15 kDa selenoprotein (Sep15 may also play a role in promoting colon cancer. The current study investigated whether the effects of reversing the cancer phenotype observed when Sep15 was removed in mouse colon cancer cells, were recapitulated in HCT116 and HT29 human colorectal carcinoma cells. Targeted down-regulation of Sep15 using RNAi technology in these human colon cancer cell lines resulted in similarly decreased growth under anchorage-dependent and anchorage-independent conditions. However, the magnitude of reduction in cell growth was much less than in the mouse colon cancer cell line investigated previously. Furthermore, changes in cell cycle distribution were observed, indicating a delayed release of Sep15 deficient cells from the G0/G1 phase after synchronization. The potential mechanism by which human colon cancer cells lacking Sep15 revert their cancer phenotype will need to be explored further.

  1. Growth on mannitol-rich media elicits a genome-wide transcriptional response in Burkholderia multivorans that impacts on multiple virulence traits in an exopolysaccharide-independent manner. (United States)

    Denman, Carmen C; Robinson, Matthew T; Sass, Andrea M; Mahenthiralingam, Eshwar; Brown, Alan R


    In common with other members of the Burkholderia cepacia complex (BCC), Burkholderia multivorans is capable of producing exopolysaccharide (EPS) when grown on certain mannitol-rich media. The significance of the resulting mucoid phenotype and the genome-wide response to mannitol has never been characterized despite its clinical relevance following the approval of a dried-powder preparation of mannitol as an inhaled osmolyte therapy for cystic fibrosis (CF) patients. In the present study we defined the transcriptional response of B. multivorans ATCC 17616, a model genome-sequenced strain of environmental origin, to growth on mannitol-rich yeast extract media (MYEM). EPS-dependent and -independent impact of MYEM on virulence-associated traits was assessed in both strain ATCC 17616 and the CF isolate B. multivorans C1576. Our studies revealed a significant transcriptional response to MYEM encompassing approximately 23 % of predicted genes within the genome. Strikingly, this transcriptional response identified that EPS induction occurs in ATCC 17616 without the upregulation of the bce-I and bce-II EPS gene clusters, despite their pivotal role in EPS biosynthesis. Of approximately 20 differentially expressed putative virulence factors, 16 exhibited upregulation including flagella, ornibactin, oxidative stress proteins and phospholipases. MYEM-grown B. multivorans also exhibited enhanced motility, biofilm formation and epithelial cell invasion. In contrast to these potential virulence enhancements, MYEM-grown B. multivorans C1576 showed attenuated virulence in the Galleria mellonella infection model. All of the observed phenotypic responses occurred independently of EPS production, highlighting the profound impact that mannitol-based growth has on the physiology and virulence of B. multivorans.

  2. Ets-1 controls breast cancer cell balance between invasion and growth. (United States)

    Furlan, Alessandro; Vercamer, Chantal; Bouali, Fatima; Damour, Isabelle; Chotteau-Lelievre, Anne; Wernert, Nicolas; Desbiens, Xavier; Pourtier, Albin


    Ets-1 overexpression in human breast cancers is associated with invasiveness and poor prognosis. By overexpressing Ets-1 or a dominant negative mutant in MMT breast cancer cells, we previously highlighted the key role of Ets-1 in coordinating multiple invasive features of these cells. Interestingly, we also noticed that Ets-1 decreased the density of breast cancer cells cultured in three-dimensional extracellular matrix gels. The 3D context was instrumental to this phenomenon, as such downregulation was not observed in cells grown on two-dimensional plastic or matrix-coated dishes. Ets-1 overexpression was deleterious to anchorage-independent growth of MMT cells in soft agar, a standard model for in vitro tumorigenicity. The relevance of this mechanism was confirmed in vivo, during primary tumor growth and in a metastatic assay of lung colonization. In these models, Ets-1 was associated with epithelial-to-mesenchymal transition features and modulated the ratio of Ki67-positive cells, while hardly affecting in vivo apoptotic cell death. Finally, siRNA-mediated knockdown of Ets-1 in human breast cancer cell lines also decreased colony growth, both in anchorage-independent assays and 3D extracellular matrix cultures. These in vitro and in vivo observations shed light on an unsuspected facet of Ets-1 in breast tumorigenesis. They show that while promoting malignancy through the acquisition of invasive features, Ets-1 also attenuates breast tumor cell growth and could therefore repress the growth of primary tumors and metastases. This work also demonstrates that 3D models may reveal mechanisms of tumor biology that are cryptic in standard 2D models. © 2014 UICC.

  3. Graded hedgehog and fibroblast growth factor signaling independently regulate pituitary cell fates and help establish the pars distalis and pars intermedia of the zebrafish adenohypophysis. (United States)

    Guner, Burcu; Ozacar, A Tuba; Thomas, Jeanne E; Karlstrom, Rolf O


    The vertebrate adenohypophysis forms as a placode at the anterior margin of the neural plate, requiring both hedgehog (Hh) and fibroblast growth factor (Fgf) mediated cell-cell signaling for induction and survival of endocrine cell types. Using small molecule inhibitors to modulate signaling levels during zebrafish development we show that graded Hh and Fgf signaling independently help establish the two subdomains of the adenohypophysis, the anteriorly located pars distalis (PD) and the posterior pars intermedia (PI). High levels of Hh signaling are required for formation of the PD and differentiation of anterior endocrine cell types, whereas lower levels of Hh signaling are required for formation of the PI and differentiation of posterior endocrine cell types. In contrast, high Fgf signaling levels are required for formation of the PI and posterior endocrine cell differentiation, whereas anterior regions require lower levels of Fgf signaling. Based on live observations and marker analyses, we show that the PD forms first at the midline closest to the central nervous system source of Sonic hedgehog. In contrast the PI appears to form from more lateral/posterior cells close to a central nervous system source of Fgf3. Together our data show that graded Hh and Fgf signaling independently direct induction of the PD and PI and help establish endocrine cell fates along the anterior/posterior axis of the zebrafish adenohypophysis. These data suggest that there are distinct origins and signaling requirements for the PD and PI.

  4. Epidermal Growth Factor and Estrogen Act by Independent Pathways to Additively Promote the Release of the Angiogenic Chemokine CXCL8 by Breast Tumor Cells

    Directory of Open Access Journals (Sweden)

    Karin Haim


    Full Text Available The tumor microenvironment contains multiple cancer-supporting factors, whose joint activities promote malignancy. Here, we show that epidermal growth factor (EGF and estrogen upregulate in an additive manner the transcription and the secretion of the angiogenic chemokine CXCL8 (interleukin 8 [IL-8] in breast tumor cells. In view of published findings on cross-regulatory interactions between EGF receptors and estrogen receptors in breast tumor cells, we asked whether the additive effects of EGF and estrogen were due to their ability to (1 induce intracellular cross talk and amplify shared regulatory pathways or (2 act in independent mechanisms, which complement each other. We found that stimulation by EGF alone induced the release of CXCL8 through signaling pathways involving ErbB2, ErbB1, Erk, and phosphoinositide 3-kinase (PI3K. ErbB2 and Erk were also involved in estrogen activities on CXCL8 but to a lower extent than with EGF. However, in the joint stimulatory setup, the addition of estrogen to EGF has led to partial (ErbB2, ErbB1, Erk or complete (PI3K shutoff of the involvement of these activation pathways in CXCL8 up-regulation. Furthermore, when costimulation by EGF + estrogen was applied, the effects of estrogen were channeled to regulation of CXCL8 at the transcription level, acting through the transcription factor estrogen receptor α (ERα. In parallel, in the joint stimulation, EGF acted independently at the transcription level through AP-1, to upregulate CXCL8 expression. The independent activities of EGF and estrogen on CXCL8 transcription reinforce the need to introduce simultaneous targeting of ErbBs and ERα to achieve effective therapy in breast cancer.

  5. Fibroblast Growth Factor Receptor 1 (FGFR1), Partly Related to Vascular Endothelial Growth Factor Receptor 2 (VEGFR2) and Microvessel Density, is an Independent Prognostic Factor for Non-Small Cell Lung Cancer (United States)

    Pu, Dan; Liu, Jiewei; Li, Zhixi; Zhu, Jiang; Hou, Mei


    Background This study aimed to explore the correlation between FGFR1 and clinical features, including survival analysis and the promotion of angiogenesis by fibroblast growth factor receptor 1 (FGFR1) and vascular endothelial growth factor receptor 2 (VEGFR2). FGFR1 gene amplification has been found in non-small cell lung cancer (NSCLC). However, the prognostic value of FGFR1 and the correlation between FGFR1 and clinical features are still controversial. Material/Methods A total of 92 patients with NSCLC who underwent R0 resection between July 2006 and July 2008 were enrolled in the study. The expression of FGFR1, VEGFR2, and CD34 was detected by immunohistochemistry. The correlations between the aforementioned markers and the patients’ clinical features were analyzed by the chi-square test. The impact factors of prognosis were evaluated by Cox regression analyses. Results The expression ratios of FGFR1 and VEGFR2 were 26.1% and 43.4%, respectively. The intensity of FGFR1 expression was related to VEGFR2 and histopathology. To some extent, the average microvessel density (MVD) had correlation to the expression of FGFR1 and VGEFR2. The pathological stages III–IV and high expression of FGFR1 were found to be independent prognostic factors. Conclusions The expression intensity of FGFR1 and VEGFR2 was associated with MVD, and the expression of FGFR1 is one of the independent prognostic indicators for NSCLC. PMID:28088809

  6. Protein kinase A (PknA) of Mycobacterium tuberculosis is independently activated and is critical for growth in vitro and survival of the pathogen in the host. (United States)

    Nagarajan, Sathya Narayanan; Upadhyay, Sandeep; Chawla, Yogesh; Khan, Shazia; Naz, Saba; Subramanian, Jayashree; Gandotra, Sheetal; Nandicoori, Vinay Kumar


    The essential mycobacterial protein kinases PknA and PknB play crucial roles in modulating cell shape and division. However, the precise in vivo functional aspects of PknA have not been investigated. This study aims to dissect the role of PknA in mediating cell survival in vitro as well as in vivo. We observed aberrant cell shape and severe growth defects when PknA was depleted. Using the mouse infection model, we observe that PknA is essential for survival of the pathogen in the host. Complementation studies affirm the importance of the kinase, juxtamembrane, and transmembrane domains of PknA. Surprisingly, the extracytoplasmic domain is dispensable for cell growth and survival in vitro. We find that phosphorylation of the activation loop at Thr(172) of PknA is critical for bacterial growth. PknB has been previously suggested to be the receptor kinase, which activates multiple kinases, including PknA, by trans-phosphorylating their activation loop residues. Using phospho-specific PknA antibodies and conditional pknB mutant, we find that PknA autophosphorylates its activation loop independent of PknB. Fluorescently tagged PknA and PknB show distinctive distribution patterns within the cell, suggesting that although both kinases are known to modulate cell shape and division, their modes of action are likely to be different. This is supported by our findings that expression of kinase-dead PknA versus kinase-dead PknB in mycobacterial cells leads to different cellular phenotypes. Data indicate that although PknA and PknB are expressed as part of the same operon, they appear to be regulating cellular processes through divergent signaling pathways.

  7. Heterotrimeric G-protein, Gα16, is a critical downstream effector of non-canonical Wnt signaling and a potent inhibitor of transformed cell growth in non small cell lung cancer.

    Directory of Open Access Journals (Sweden)

    Sreedevi Avasarala

    Full Text Available G-protein-coupled receptors (GPCR are the largest family of cell surface molecules that play important role/s in a number of biological and pathological processes including cancers. Earlier studies have highlighted the importance of Wnt7a signaling via its cognate receptor Frizzled9, a GPCR, in inhibition of cell proliferation, anchorage-independent growth, and reversal of transformed phenotype in non small cell lung cancer primarily through activation of the tumor suppressor, PPARγ. However, the G-protein effectors that couple to this important tumor suppressor pathway have not been identified, and are of potential therapeutic interest. In this study, by using two independent Wnt7a/Frizzled9-specific read-outs, we identify Gα16 as a novel downstream effector of Wnt7a/Frizzled9 signaling. Interestingly, Gα16 expression is severely down-regulated, both at the messenger RNA levels and protein levels, in many non small cell lung cancer cell lines. Additionally, through gene-specific knock-downs and expression of GTPase-deficient forms (Q212L of Gα16, we also establish Gα16 as a novel regulator of non small cell lung cancer cell proliferation and anchorage-independent cell growth. Taken together, our data not only establish the importance of Gα16 as a critical downstream effector of the non-canonical Wnt signaling pathway but also as a potential therapeutic target for the treatment of non small cell lung cancer.

  8. Independence, Peace and Economic Growth

    Institute of Scientific and Technical Information of China (English)


    Foreign Minister Yang Jiechi recently addressed China’s diplomatic achievements over the 60 years since the founding of the People’s Republic in 1949. He also made projections on the future of Chinese diplomacy. Yang’s main points follow:

  9. Thiazolidinediones alter growth and epithelial cell integrity, independent of PPAR-γ and MAPK activation, in mouse M1 cortical collecting duct cells. (United States)

    Nasrallah, Rania; Clark, Jordan; Corinaldi, Jaime; Paris, Geneviève; Miura, Pedro; Jasmin, Bernard J; Hébert, Richard L


    Peroxisome proliferator-activated receptor (PPAR)-γ is highly expressed in the collecting duct (CD), yet little is known about the effects of PPAR-γ ligands, thiazolidinediones (TZDs), on CD cell structure and function. M1 mouse cortical CD cells were treated with 5 μM troglitazone (TRO) and rosiglitazone (ROSI). First, growth was measured by [(3)H]thymidine and [(3)H]leucine incorporation, as well as analysis of cyclin D1 and the CDK inhibitor p27 by Western blot. [(3)H]thymidine incorporation was reduced by 56 and 24% by TRO and ROSI at 6 h, and [(3)H]leucine by 21 and 10%. A similar growth inhibition was also observed after 24 h for thymidine, but leucine was reduced by 48 and 24%, respectively. Likewise, cyclin D1 was diminished 60% by TRO, and p27 was elevated 1.6- and 1.7-fold in response to TRO and ROSI. Next, epithelial cell integrity was assessed by measuring different markers by Western blot analysis. While fibronectin and α-smooth muscle actin levels were unchanged, by 24 h E-cadherin was decreased by 50%, and β-catenin levels were reduced 2- and 1.5-fold in response to TRO and ROSI, respectively. GW9662, a PPAR-γ antagonist, did not reverse any of the TZD responses in M1 cells. Of interest, phosho-p38 levels were also elevated 2-fold in response to TRO and 2.3-fold to ROSI, but MAPK inhibition by PD98059 or SB203580 caused an additive inhibition of cell growth and did not alter E-cadherin or β-catenin in response to TZDs. Finally, apoptotic death was assessed by Western blot, but cleaved caspase-3 levels were unchanged from 15 min to 24 h in response to TZDs, and TRO did not affect cell viability or reactive oxygen species generation. Our data suggest that TZDs cause a disruption of M1 cell integrity that is preceded by an inhibition of cell growth. This response is independent of p38 or PPAR-γ activation.

  10. Inclusion of CFRP-Epoxy Composite for End Anchorage in NSM-Epoxy Strengthened Beams

    Directory of Open Access Journals (Sweden)

    Md. Akter Hosen


    Full Text Available Nowadays, the use of near surface mounted (NSM technique strengthening reinforced concrete (RC structural members is going very popular. The failure modes of NSM strengthened reinforced concrete (RC beams have been shown to be largely due to premature failure such as concrete cover separation. In this study, CFRP U-wrap end anchorage with CFRP fabrics was used to eliminate the concrete cover separation failure. A total of eight RC rectangular beam specimens of 125 mm width, 250 mm depth, and 2300 mm length were tested. One specimen was kept unstrengthened as a reference; three specimens were strengthened with NSM steel bars and the remaining four specimens were strengthened with NSM steel bars together with the U-wrap end anchorage. The experimental results showed that wrapped strengthened beams had higher flexural strength and superior ductility performance. The results also show that these beams had less deflection, strain, crack width, and spacing.

  11. Numerical implementation of multiple peeling theory and its application to spider web anchorages. (United States)

    Brely, Lucas; Bosia, Federico; Pugno, Nicola M


    Adhesion of spider web anchorages has been studied in recent years, including the specific functionalities achieved through different architectures. To better understand the delamination mechanisms of these and other biological or artificial fibrillar adhesives, and how their adhesion can be optimized, we develop a novel numerical model to simulate the multiple peeling of structures with arbitrary branching and adhesion angles, including complex architectures. The numerical model is based on a recently developed multiple peeling theory, which extends the energy-based single peeling theory of Kendall, and can be applied to arbitrarily complex structures. In particular, we numerically show that a multiple peeling problem can be treated as the superposition of single peeling configurations even for complex structures. Finally, we apply the developed numerical approach to study spider web anchorages, showing how their function is achieved through optimal geometrical configurations.

  12. Impedance-Based Cable Force Monitoring in Tendon-Anchorage Using Portable PZT-Interface Technique

    Directory of Open Access Journals (Sweden)

    Thanh-Canh Huynh


    Full Text Available In this paper, a portable PZT interface for tension force monitoring in the cable-anchorage subsystem is developed. Firstly, the theoretical background of the impedance-based method is presented. A few damage evaluation approaches are outlined to quantify the variation of impedance signatures. Secondly, a portable PZT interface is designed to monitor impedance signatures from the cable-anchorage subsystem. One degree-of-freedom analytical model of the PZT interface is established to explain how to represent the loss of cable force from the change in the electromechanical impedance of the PZT interface as well as reducing the sensitive frequency band by implementing the interface device. Finally, the applicability of the proposed PZT-interface technique is experimentally evaluated for cable force-loss monitoring in a lab-scaled test structure.

  13. A genetic algorithm for dynamic parameters reverse deduction of integrated anchorage system

    Institute of Scientific and Technical Information of China (English)


    In the analysis of the system of anchoring bar and wall rock in small strain and longitudinal vibration dynamic response, the influence of the cement grouting as well as the rock layer on the anchor bar can be evaluated as the two kinds of parameters: the dynamic stiffness and the damp, which are the vital reference of the anchorage quality. Based on the analytic solution to the dynamic equation of the integrated anchor bar, the new approach which combines genetic algorithm and the toolbox of Matlab is applied to solve the problem of multi-parameters reverse deduction for integrated anchorage system in dynamic testing. Using the traits of the self-organizing, self-adapting and the fast convergence speed of the genetic algorithm, the optimum of all possible solutions to dynamic parameters is obtained by calculating the project instances. Examples show that the method presented in this paper is effective and reliable.

  14. Anchorage of titanium implants with different surface characteristics: an experimental study in rabbits

    DEFF Research Database (Denmark)

    Gotfredsen, K; Berglundh, T; Lindhe, J


    ) TiO2-blasted with particles of grain size 10 to 53 microns; (3) TiO2-blasted, grain size 63 to 90 microns; (4) TiO2-blasted, grain size 90 to 125 microns; (5) titanium plasma-sprayed (TPS). The surface topography was determined by the use of an optical instrument. Twelve rabbits, divided into two...... in group B were 9 and 12 weeks. The tibiae were removed, and each implant site was dissected, fixed, and embedded in light-curing resin. Ground sections were made, and the peri-implant bone was analyzed using fluorescence and light microscopy. RESULTS: The turned implants had the lowest Sa and Sy values......: The present study demonstrated that a clear relation exists between surface roughness, described in Sa values, and implant anchorage assessed by RMT measurements. The anchorage appeared to increase with the maturation of bone tissue during healing....

  15. Daily physical activity, fasting glucose, uric acid, and body mass index are independent factors associated with serum fibroblast growth factor 21 levels. (United States)

    Cuevas-Ramos, Daniel; Almeda-Valdes, Paloma; Gómez-Pérez, Francisco J; Meza-Arana, Clara Elena; Cruz-Bautista, Ivette; Arellano-Campos, Olimpia; Navarrete-López, Mariana; Aguilar-Salinas, Carlos A


    Fibroblast growth factor 21 (FGF21) levels have been linked with beneficial effects on glucose and lipid metabolism in animals. It is elevated in humans with the metabolic syndrome. This study investigates independent factors associated with serum FGF21 levels. Cross-sectional study done in healthy blue-collar workers. A medical history was taken, and FGF21 (measured using an ELISA commercial kit), glucose, uric acid, plasma lipids, total/high-molecular weight (HMW) adiponectin, and retinal-binding protein 4 (RBP4) were measured in 210 individuals with (n=81) and without (n=129) metabolic syndrome. The median of serum FGF21 levels were higher in subjects with metabolic syndrome (339.5 vs 276.4 ng/l, P=0.01). Serum FGF21 levels correlated positively with body mass index (BMI; r=0.23, P=0.001) and age (r=0.17, P=0.01). After adjusting for age and BMI, a significant positive correlation persisted for fasting glucose, uric acid, and physical activity in both males (r=0.21, r=0.11, and r=0.19, all Pphysical activity (SB=0.223; P=0.004) are independent factors influencing serum FGF21 levels (F=10.05, r(2)=0.19, Pfasting hyperglycemia > or =100 mg/dl, excess body weight with BMI > or =25 kg/m(2), and uric acid > or =5.5 mg/dl predicted higher serum FGF21 levels. Serum FGF21 levels are influenced by BMI, fasting glycemia, uric acid, and physical activity.

  16. Impedance monitoring at tendon-anchorage via mountable PZT interface and temperature-effect compensation (United States)

    Huynh, Thanh-Canh; Nguyen, Tuan-Cuong; Choi, Sang-Hoon; Kim, Jeong-Tae


    In this study, the pre-stress force in pre-stressed concrete (PSC) girders is monitored via mountable PZT interface under varying temperature. Firstly, an impedance-based technique using mountable PZT interface is proposed for pre-stress-loss monitoring in tendon-anchorage systems. A cross correlation-based temperature-effect compensation algorithm using an effective frequency shift (EFS) of impedance signatures is visited. Secondly, lab-scale experiments are performed on a PSC girder instrumented with a mountable PZT interface at tendon-anchorage. A series of temperature variation and pre-stress-loss events are simulated for the lab-scale PSC girder. Thirdly, the feasibility of the mountable PZT interface for pre-stress-loss monitoring in tendon-anchorage is experimentally verified under constant temperature conditions. Finally, the PZT interface device is examined for pre-stress-loss monitoring under temperature changes to validate its applicability. The temperature effect on impedance signatures is compensated by minimizing cross-correlation deviation between impedance patterns of the mountable PZT interface.

  17. The Plurality of Harbors at Caesarea: The Southern Anchorage in Late Antiquity (United States)

    Ratzlaff, Alexandra; Galili, Ehud; Waiman-Barak, Paula; Yasur-Landau, Assaf


    The engineering marvel of Sebastos, or Portus Augusti as it was called in Late Antiquity (284-638 CE), dominated Caesarea's harbor center along modern Israel's central coast but it was only one part of a larger maritime complex. The Southern Anchorage provides a case study as one portion of the Caesarea complex, as well as a node within the regional network of anchorages and small harbors. Ceramics recovered from here show a high percentage of locally, and provincially, produced storage jars engaged in maritime trade. The ceramic evidence points towards an intensified regional trade or cabotage rather than favouring long distance trade from large port to port. Working out of these small harbors, opportunities arose for greater flexibility in specialization of commodities and materials passing through the network of subsidiary ports, contributing to a more diversified market economy. This analysis provides another example in the growing focus on how these simple and semi-modified anchorages in the Eastern Mediterranean were often the predominant economic networks connecting hinterland and coastal trade.

  18. Strontium ranelate improved tooth anchorage and reduced root resorption in orthodontic treatment of rats. (United States)

    Kirschneck, Christian; Wolf, Michael; Reicheneder, Claudia; Wahlmann, Ulrich; Proff, Peter; Roemer, Piero


    The anchorage mechanisms currently used in orthodontic treatment have various disadvantages. The objective of this study was to determine the applicability of the osteoporosis medication strontium ranelate in pharmacologically induced orthodontic tooth anchorage. In 48 male Wistar rats, a constant orthodontic force of 0.25 N was reciprocally applied to the upper first molar and the incisors by means of a Sentalloy(®) closed coil spring for two to four weeks. 50% of the animals received strontium ranelate at a daily oral dosage of 900 mg per kilogramme of body weight. Bioavailability was determined by blood analyses. The extent of tooth movement was measured both optometrically and cephalometrically (CBCT). Relative alveolar gene expression of osteoclastic markers and OPG-RANKL was assessed by qRT-PCR and root resorption area and osteoclastic activity were determined in TRAP-stained histologic sections of the alveolar process. Compared to controls, the animals treated with strontium ranelate showed up to 40% less tooth movement after four weeks of orthodontic treatment. Gene expression and histologic analyses showed significantly less osteoclastic activity and a significantly smaller root resorption area. Blood analyses confirmed sufficient bioavailability of strontium ranelate. Because of its pharmacologic effects on bone metabolism, strontium ranelate significantly reduced tooth movement and root resorption in orthodontic treatment of rats. Strontium ranelate may be a viable agent for inducing tooth anchorage and reducing undesired root resorption in orthodontic treatment. Patients under medication of strontium ranelate have to expect prolonged orthodontic treatment times.

  19. Dietary histidine requirement to reduce the risk and severity of cataracts is higher than the requirement for growth in Atlantic salmon smolts, independently of the dietary lipid source. (United States)

    Remø, S C; Hevrøy, E M; Olsvik, P A; Fontanillas, R; Breck, O; Waagbø, R


    The present study was carried out to investigate whether the dietary histidine requirement to reduce cataract development is higher than that for growth in Atlantic salmon smolts (Salmo salar L.) after seawater transfer and whether dietary vegetable oils contribute to cataractogenesis. Duplicate groups of salmon smolts were fed ten experimental diets with either fish oil (FO) or a vegetable oil (VO) mix replacing 70 % FO and histidine at five target levels (10, 12, 14, 16 and 18 g His/kg diet) for 13 weeks after seawater transfer. The VO diet-fed fish exhibited somewhat inferior growth and feed intakes compared with the FO diet-fed fish, irrespective of the dietary histidine concentration. Both cataract prevalence and severity were negatively correlated with the dietary histidine concentration, while lens N-acetyl-histidine (NAH) concentrations were positively correlated with it. The fatty acid profiles of muscle, heart and lens reflected that of the dietary oils to a descending degree and did not affect the observed cataract development. Muscle, heart and brain histidine concentrations reflected dietary histidine concentrations, while the corresponding tissue imidazole (anserine, carnosine and NAH) concentrations appeared to saturate differently with time. The expression level of liver histidase was not affected by the dietary histidine concentration, while the liver antioxidant response was affected in the VO diet-fed fish on a transcriptional level. The lowest severity of cataracts could be achieved by feeding 13·4 g His/kg feed, independently of the dietary lipid source. However, the present study also suggests that the dietary histidine requirement to minimise the risk of cataract development is 14·4 g His/kg feed.

  20. Expression of connective tissue growth factor in tumor tissues is an independent predictor of poor prognosis in patients with gastric cancer

    Institute of Scientific and Technical Information of China (English)

    Lu-Ying Liu; Yan-Chun Han; Shu-Hua Wu; Zeng-Hua Lv


    AIM: To examine the expression of connective tissue growth factor (CTGF), also known as CCN2, in gastric carcinoma (GC), and the correlation between the expression of CTGF, dinicopathologic features and clinical outcomes of patients with GC.METHODS: One hundred and twenty-two GC patients were included in the present study. All patients were followed up for at least 5 years. Proteins of CTGF were detected using the Powervision two-step immunostaining method.RESULTS: Of the specimens from 122 GC patients analyzed for CTGF expression, 58 (58/122, 47.5%) had a high CTGF expression in cytoplasm of gastric carcinoma cells and 64 (64/122, 52.5%) had a low CTGF expression. Patients with a high CTGF expression showed a higher incidence of lymph node metastasis than those with a low CTGF expression {P = 0.032). Patients with a high CTGF expression had significantly lower 5-year survival rate than those with a low CTGF expression (27.6% vs 46.9%, P = 0.0178), especially those staging I + H + m (35.7% vs 65.2%, P = 0.0027).CONCLUSION: GC patients with an elevated CTGF expression have more lymph node metastases and a shorter survival time. CTGF seems to be an independent prognostic factor for the successful differentiation of high-risk GC patients staging I + n + m. Over-expression of CTGF in human GC cells results in an increased aggressive ability.

  1. Insulin-Like Growth Factor-I Induces Arginase Activity in Leishmania amazonensis Amastigote-Infected Macrophages through a Cytokine-Independent Mechanism

    Directory of Open Access Journals (Sweden)

    Celia Maria Vieira Vendrame


    Full Text Available Leishmania (Leishmania amazonensis exhibits peculiarities in its interactions with hosts. Because amastigotes are the primary form associated with the progression of infection, we studied the effect of insulin-like growth factor (IGF-I on interactions between L. (L. amazonensis amastigotes and macrophages. Upon stimulation of infected macrophages with IGF-I, we observed decreased nitric oxide production but increased arginase expression and activity, which lead to increased parasitism. However, stimulation of amastigote-infected macrophages with IGF-I did not result in altered cytokine levels compared to unstimulated controls. Because IGF-I is present in tissue fluids and also within macrophages, we examined the possible effect of this factor on phosphatidylserine (PS exposure on amastigotes, seen previously in tissue-derived amastigotes leading to increased parasitism. Stimulation with IGF-I induced PS exposure on amastigotes but not on promastigotes. Using a PS-liposome instead of amastigotes, we observed that the PS-liposome but not the control phosphatidylcholine-liposome led to increased arginase activity in macrophages, and this process was not blocked by anti-TGF-β antibodies. Our results suggest that in L. (L. amazonensis amastigote-infected macrophages, IGF-I induces arginase activity directly in amastigotes and in macrophages through the induction of PS exposure on amastigotes in the latter, which could lead to the alternative activation of macrophages through cytokine-independent mechanisms.

  2. Farnesoid X receptor-dependent and -independent pathways mediate the transcriptional control of human fibroblast growth factor 19 by vitamin A. (United States)

    Jahn, Daniel; Sutor, Dominic; Dorbath, Donata; Weiß, Johannes; Götze, Oliver; Schmitt, Johannes; Hermanns, Heike M; Geier, Andreas


    Fibroblast growth factor 19 (FGF19) is a gut-derived hormone that controls bile acid (BA), carbohydrate and lipid metabolism. Whereas strong evidence supports a key role of BAs and farnesoid X receptor (FXR) for the control of FGF19 expression, information on other regulators is limited. In mice, FGF15 expression (ortholog of human FGF19) is induced by vitamin A (VitA) in an FXR-dependent manner. However, the significance of this finding for human FGF19 is currently unclear. Here, we demonstrate that VitA derivatives induce FGF19 in human intestinal cell lines by a direct transcriptional mechanism. In contrast to mouse FGF15, however, this direct regulation is not dependent on FXR but mediated by retinoic acid receptors (RARs) and their interaction with a novel DR-5 element in the human FGF19 gene. In addition to this direct effect, VitA derivatives impacted on the BA-mediated control of FGF19 by regulation of FXR protein levels. In conclusion, VitA regulates human FGF19 expression through FXR-dependent and -independent pathways. Moreover, we suggest that considerable mechanistic differences exist between humans and mice with regard to the nuclear receptors controlling the VitA-FGF15/19 axis. These findings may implicate a clinical relevance of RAR-activating VitA derivatives for the regulation of FGF19 levels in humans.

  3. Combinatorial treatment using targeted MEK and SRC inhibitors synergistically abrogates tumor cell growth and induces mesenchymal-epithelial transition in non-small-cell lung carcinoma. (United States)

    Chua, Kian Ngiap; Kong, Li Ren; Sim, Wen Jing; Ng, Hsien Chun; Ong, Weijie Richard; Thiery, Jean Paul; Huynh, Hung; Goh, Boon Cher


    Oncogenesis in non-small cell lung cancer (NSCLC) is regulated by a complex signal transduction network. Single-agent targeted therapy fails frequently due to treatment insensitivity and acquired resistance. In this study, we demonstrate that co-inhibition of the MAPK and SRC pathways using a PD0325901 and Saracatinib kinase inhibitor combination can abrogate tumor growth in NSCLC. PD0325901/Saracatinib at 0.25:1 combination was screened against a panel of 28 NSCLC cell lines and 68% of cell lines were found to be sensitive (IC50 cell migration and matrigel invasion. The co-inhibition of MAPK and SRC induced strong G1/G0 cell cycle arrest in the NSCLC lines, inhibited anchorage independent growth and delayed tumor growth in H460 and H358 mouse xenografts. These data provide rationale for further investigating the combination of MAPK and SRC pathway inhibitors in advanced stage NSCLC.

  4. Effect of receptor-selective retinoids on growth and differentiation pathways in mouse melanoma cells. (United States)

    Desai, S H; Boskovic, G; Eastham, L; Dawson, M; Niles, R M


    Treatment of B16 mouse melanoma cells with all-trans-retinoic acid (ATRA) results in inhibition of cell proliferation and induction of differentiation. Accompanying these events is an induction of retinoic acid receptor beta (RARbeta) expression, an increase in protein kinase Calpha (PKCalpha) expression, and enhanced activator protein-1 (AP-1) transcriptional activity. These cells express nuclear RARalpha and RARgamma and nuclear retinoid X receptors (RXR) alpha and beta constitutively. We tested the ability of receptor-selective retinoids to induce the biochemical changes found in ATRA-treated melanoma cells and also tested their effectiveness in decreasing anchorage-dependent and -independent growth. The RXR-selective ligand (2E,4E)-6-(5,6,7,8-tetrahydro-3,5,5,8, 8-pentamethyl-2-naphthalenyl)-3,7-dimethyl-2,4,6-octatrienoic acid (SR11246) was most effective at inhibiting anchorage-dependent growth, whereas the RARgamma-selective ligand 6-[(5,6,7, 8-tetrahydro-5,5,8, 8-tetramethyl-2-naphthalenyl)(hydroxyimino)methyl]-2-naphthalen ecarbo xylic acid (SR11254) was most potent at inhibiting anchorage-independent growth. In contrast, 4-(5,6,7,8-tetrahydro-5,5, 8,8-tetramethyl-2-naphthalenecarboxamido)-benzoic acid (Am580), an RARalpha-selective ligand, was the most effective receptor-selective agonist for inducing RARbeta mRNA and increasing the amount of PKCalpha protein. All of the retinoids induced a concentration-dependent increase in AP-1 transcriptional activity, with little difference in effectiveness among the receptor-selective retinoids. A synergistic increase in the amount of PKCalpha was found when an RAR-selective agonist was combined with an RXR-selective agonist. One possible explanation for this result is that an RXR-RAR heterodimer in which both receptors are liganded is required for maximum expression of this critical component of the ATRA-induced differentiation pathway. Our data suggest that synthetic retinoids can activate different growth and

  5. Metabolism Kinetics of Glucose in Anchorage-dependent Cell Cultures

    Institute of Scientific and Technical Information of China (English)

    孙祥明; 张元兴


    The kinetic model of glucose metabolism was established and successfully applied to batchcultures of rCHO and rBHK cells. It was found that a large amount of glucose was utilized for cellmaintenance, and the overwhelming majority of maintenance energy from glucose was by its anaerobicmetabolism in both rBHK and rCHO cell cultures. The overall maintenance coefficients from aerobicmetabolism were 1.9×10-13 mmol/(cell.h) for rCHO cells and 7×10-13 mmol/(cell.h) for rBHK cells. Inaddition, all Go/T and Eo/T gradually increased with the same trend as the cell growth in the culture ofboth rCHO and rBHK cells. The overall molecule yield coefficients of lactate to glucose were 1.61 for rCHO cells and 1.38 for rBHK cells. The yield coefficients of cell to glucose were 4.5×108 cells/mmol for rCHO cells and 1.9 × 108 cells/mmol for rBHK cells, respectively.

  6. Ectodomains of the LDL receptor-related proteins LRP1b and LRP4 have anchorage independent functions in vivo.

    Directory of Open Access Journals (Sweden)

    Martin F Dietrich

    Full Text Available BACKGROUND: The low-density lipoprotein (LDL receptor gene family is a highly conserved group of membrane receptors with diverse functions in developmental processes, lipoprotein trafficking, and cell signaling. The low-density lipoprotein (LDL receptor-related protein 1b (LRP1B was reported to be deleted in several types of human malignancies, including non-small cell lung cancer. Our group has previously reported that a distal extracellular truncation of murine Lrp1b that is predicted to secrete the entire intact extracellular domain (ECD is fully viable with no apparent phenotype. METHODS AND PRINCIPAL FINDINGS: Here, we have used a gene targeting approach to create two mouse lines carrying internally rearranged exons of Lrp1b that are predicted to truncate the protein closer to the N-terminus and to prevent normal trafficking through the secretary pathway. Both mutations result in early embryonic lethality, but, as expected from the restricted expression pattern of LRP1b in vivo, loss of Lrp1b does not cause cellular lethality as homozygous Lrp1b-deficient blastocysts can be propagated normally in culture. This is similar to findings for another LDL receptor family member, Lrp4. We provide in vitro evidence that Lrp4 undergoes regulated intramembraneous processing through metalloproteases and gamma-secretase cleavage. We further demonstrate negative regulation of the Wnt signaling pathway by the soluble extracellular domain. CONCLUSIONS AND SIGNIFICANCE: Our results underline a crucial role for Lrp1b in development. The expression in mice of truncated alleles of Lrp1b and Lrp4 with deletions of the transmembrane and intracellular domains leads to release of the extracellular domain into the extracellular space, which is sufficient to confer viability. In contrast, null mutations are embryonically (Lrp1b or perinatally (Lrp4 lethal. These findings suggest that the extracellular domains of both proteins may function as a scavenger for signaling ligands or signal modulators in the extracellular space, thereby preserving signaling thresholds that are critical for embryonic development, as well as for the clear, but poorly understood role of LRP1b in cancer.

  7. Peroxisome proliferator-activated receptor-gamma inhibits transformed growth of non-small cell lung cancer cells through selective suppression of Snail. (United States)

    Choudhary, Rashmi; Li, Howard; Winn, Robert A; Sorenson, Amber L; Weiser-Evans, Mary C M; Nemenoff, Raphael A


    Work from our laboratory and others has demonstrated that activation of the nuclear receptor peroxisome proliferator-activated receptor-gamma (PPARgamma) inhibits transformed growth of non-small cell lung cancer (NSCLC) cell lines in vitro and in vivo. We have demonstrated that activation of PPARgamma promotes epithelial differentiation of NSCLC by increasing expression of E-cadherin, as well as inhibiting expression of COX-2 and nuclear factor-kappaB. The Snail family of transcription factors, which includes Snail (Snail1), Slug (Snail2), and ZEB1, is an important regulator of epithelial-mesenchymal transition, as well as cell survival. The goal of this study was to determine whether the biological responses to rosiglitazone, a member of the thiazolidinedione family of PPARgamma activators, are mediated through the regulation of Snail family members. Our results indicate that, in two independent NSCLC cell lines, rosiglitazone specifically decreased expression of Snail, with no significant effect on either Slug or ZEB1. Suppression of Snail using short hairpin RNA silencing mimicked the effects of PPARgamma activation, in inhibiting anchorage-independent growth, promoting acinar formation in three-dimensional culture, and inhibiting invasiveness. This was associated with the increased expression of E-cadherin and decreased expression of COX-2 and matrix metaloproteinases. Conversely, overexpression of Snail blocked the biological responses to rosiglitazone, increasing anchorage-independent growth, invasiveness, and promoting epithelial-mesenchymal transition. The suppression of Snail expression by rosiglitazone seemed to be independent of GSK-3 signaling but was rather mediated through suppression of extracellular signal-regulated kinase activity. These findings suggest that selective regulation of Snail may be critical in mediating the antitumorigenic effects of PPARgamma activators.

  8. Peroxisome Proliferator-Activated Receptor-γ Inhibits Transformed Growth of Non-Small Cell Lung Cancer Cells through Selective Suppression of Snail

    Directory of Open Access Journals (Sweden)

    Rashmi Choudhary


    Full Text Available Work from our laboratory and others has demonstrated that activation of the nuclear receptor peroxisome proliferator-activated receptor-γ (PPARγ inhibits transformed growth of non-small cell lung cancer (NSCLC cell lines in vitro and in vivo. We have demonstrated that activation of PPARγ promotes epithelial differentiation of NSCLC by increasing expression of E-cadherin, as well as inhibiting expression of COX-2 and nuclear factor-κB. The Snail family of transcription factors, which includes Snail (Snail1, Slug (Snail2, and ZEB1, is an important regulator of epithelial-mesenchymal transition, as well as cell survival. The goal of this study was to determine whether the biological responses to rosiglitazone, a member of the thiazolidinedione family of PPARγ activators, are mediated through the regulation of Snail family members. Our results indicate that, in two independent NSCLC cell lines, rosiglitazone specifically decreased expression of Snail, with no significant effect on either Slug or ZEB1. Suppression of Snail using short hairpin RNA silencing mimicked the effects of PPARγ activation, in inhibiting anchorage-independent growth, promoting acinar formation in three-dimensional culture, and inhibiting invasiveness. This was associated with the increased expression of E-cadherin and decreased expression of COX-2 and matrix metaloproteinases. Conversely, overexpression of Snail blocked the biological responses to rosiglitazone, increasing anchorage-independent growth, invasiveness, and promoting epithelial-mesenchymal transition. The suppression of Snail expression by rosiglitazone seemed to be independent of GSK-3 signaling but was rather mediated through suppression of extracellular signal-regulated kinase activity. These findings suggest that selective regulation of Snail may be critical in mediating the antitumorigenic effects of PPARγ activators.

  9. Promoter-dependent and -independent activation of insulin-like growth factor binding protein-5 gene expression by prostaglandin E2 in primary rat osteoblasts (United States)

    McCarthy, T. L.; Casinghino, S.; Mittanck, D. W.; Ji, C. H.; Centrella, M.; Rotwein, P.


    Insulin-like growth factor (IGF) action is mediated by high affinity cell surface IGF receptors and modulated by a family of secreted IGF binding proteins (IGFBPs). IGFBP-5, the most conserved of six IGFBPs characterized to date, uniquely potentiates the anabolic actions of IGF-I for skeletal cells. In osteoblasts, IGFBP-5 production is stimulated by prostaglandin E2 (PGE2), a local factor that mediates certain effects induced by parathyroid hormone, cytokines such as interleukin-1 and transforming growth factor-beta, and mechanical strain. In this study, we show that transcriptional and post-transcriptional events initiated by PGE2 collaborate to enhance IGFBP-5 gene expression in primary fetal rat osteoblast cultures. PGE2 treatment stimulated up to a 7-fold rise in steady-state levels of IGFBP-5 mRNA throughout 32 h of incubation. Analysis of nascent IGFBP-5 mRNA suggested that PGE2 had only a modest stimulatory effect on IGFBP-5 gene transcription, and transient transfection studies with IGFBP-5 promoter-reporter genes confirmed that PGE2 enhanced promoter activity by approximately 2-fold. Similar stimulatory effects were seen with forskolin. A DNA fragment with only 51 base pairs of the 5'-flanking sequence retained hormonal responsiveness, which may be mediated by a binding site for transcription factor AP-2 located at positions -44 to -36 in the proximal IGFBP-5 promoter. Incubation of osteoblasts with the mRNA transcriptional inhibitor 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole demonstrated that PGE2 enhanced IGFBP-5 mRNA stability by 2-fold, increasing the t1/2 from 9 to 18 h. The effects of PGE2 on steady-state IGFBP-5 transcripts were abrogated by preincubating cells with cycloheximide, indicating that the effects of PGE2 on both gene transcription and mRNA stability required ongoing protein synthesis. Therefore, both promoter-dependent and -independent pathways converge to enhance IGFBP-5 gene expression in response to PGE2 in osteoblasts.

  10. Dialysate vascular endothelial growth factor is an independent determinant of serum albumin levels and predicts future withdrawal from peritoneal dialysis in uremic patients. (United States)

    Hazama, Takuma; Fukami, Kei; Yamagishi, Sho-ichi; Kusumoto, Takuo; Sakai, Kazuko; Adachi, Takeki; Sonoda, Kazuhiro; Kasuga, Syumon; Ueda, Seiji; Okuda, Seiya


    Peritoneal protein loss due to high peritoneal permeability may contribute to hypoalbuminemia and early withdrawal from peritoneal dialysis (PD) therapy in end stage renal disease (ESRD) patients. We have found that pigment epithelium-derived factor (PEDF) has anti-vasopermeability properties both in cell culture and animal models by counteracting the biological actions of vascular endothelial growth factor (VEGF). However, it remains unknown which clinical variables, including dialysate VEGF and PEDF, are associated with decreased serum albumin levels and could predict early withdrawal from the PD in ESRD patients. We address these issues. Twenty-seven ESRD patients undergoing PD were enrolled. Clinical variables were measured at 6 months after commencing PD. We examined the independent correlates of serum albumin in PD patients and then prospectively investigated the predictors of withdrawal from the PD therapy over 4 years. Dialysate VEGF was associated with peritoneal solute transport rate (P = 0.002), serum albumin (inversely, P 27 pg/mL), low serum albumin (≤ 3.31 g/dL) and low hemoglobin (≤ 11.2 g/dL) were correlated with withdrawal from the PD therapy during the 4 years. The odds ratio of dialysate VEGF for early withdrawal from the PD was 6.310 (P = 0.035). The present study demonstrated that increased dialysate VEGF was associated with decreased serum albumin and early withdrawal from the PD therapy. Inhibition of peritoneal VEGF production may be a therapeutic target in PD patients. © 2013 The Authors. Therapeutic Apheresis and Dialysis © 2013 International Society for Apheresis.

  11. Growth factor independence 1 protects hematopoietic stem cells against apoptosis but also prevents the development of a myeloproliferative-like disease. (United States)

    Khandanpour, Cyrus; Kosan, Christian; Gaudreau, Marie-Claude; Dührsen, Ulrich; Hébert, Josée; Zeng, Hui; Möröy, Tarik


    The regulation of gene transcription is elementary for the function of hematopoietic stem cells (HSCs). The transcriptional repressor growth factor independence 1 (Gfi1) restricts HSC proliferation and is essential to maintain their self-renewal capacity and multipotency after transplantation. In addition, Gfi1(-/-) HSCs are severely compromised in their ability to compete with wild-type (wt) HSCs after transplantation. We now report that Gfi1 protects HSCs against stress-induced apoptosis, probably, by repressing the proapoptotic target gene Bax, since irradiated Gfi1(-/-) HSCs display higher expression of Bax and show a higher rate of apoptosis than wt HSCs. This protective function of Gfi1 appears to be functionally relevant since Gfi1(-/-) HSCs that express Bcl-2, which antagonizes the effects of Bax, regain their ability to self renew and to initiate multilineage differentiation after transplantation. Surprisingly, Gfi1(-/-) xBcl-2 transgenic mice also show a strong, systemic expansion of Mac-1(+) Gr-1(-) myeloid cells in bone marrow and peripheral lymphoid organs. These cells express high levels of the proleukemogenic transcription factor Hoxa9 and, in older mice, appear as atypical monocytoid-blastoid cells in the peripheral blood. As a result of this massive expansion of myeloid cells, all Gfi1(-/-) xBcl-2 mice eventually succumb to a myeloproliferative-like disease resembling a preleukemic state. In summary, our data demonstrate that Gfi1's ability to protect against apoptosis is essential for HSC function. In addition, our finding show that Gfi1 prevents the development of myeloproliferative diseases and provides evidence how Gfi1 deficiency could be linked to myeloid leukemia.

  12. CKS1B, overexpressed in aggressive disease, regulates multiple myeloma growth and survival through SKP2- and p27Kip1-dependent and -independent mechanisms (United States)

    Colla, Simona; Wu, Xiaosong; Chen, Bangzheng; Stewart, James P.; Kuehl, W. Michael; Barlogie, Bart


    Overexpression of CKS1B, a gene mapping within a minimally amplified region between 153 to 154 Mb of chromosome 1q21, is linked to a poor prognosis in multiple myeloma (MM). CKS1B binds to and activates cyclin-dependent kinases and also interacts with SKP2 to promote the ubiquitination and proteasomal degradation of p27Kip1. Overexpression of CKS1B or SKP2 contributes to increased p27Kip1 turnover, cell proliferation, and a poor prognosis in many tumor types. Using 4 MM cell lines harboring MAF-, FGFR3/MMSET-, or CCND1-activating translocations, we show that lentiviral delivery of shRNA directed against CKS1B resulted in ablation of CKS1B mRNA and protein with concomitant stabilization of p27Kip1, cell cycle arrest, and apoptosis. Although shRNA-mediated knockdown of SKP2 and forced expression of a nondegradable form of p27Kip1 (p27T187A) led to cell cycle arrest, apoptosis was modest. Of importance, while knockdown of SKP2 or overexpression of p27T187A induced cell cycle arrest in KMS28PE, an MM cell line with biallelic deletion of CDKN1B/p27Kip1, CKS1B ablation induced strong apoptosis. These data suggest that CKS1B influences myeloma cell growth and survival through SKP2- and p27Kip1-dependent and -independent mechanisms and that therapeutic strategies aimed at abolishing CKS1B function may hold promise for the treatment of high-risk disease for which effective therapies are currently lacking. PMID:17303695

  13. A cationic-independent mannose 6-phosphate receptor inhibitor (PXS64 ameliorates kidney fibrosis by inhibiting activation of transforming growth factor-β1.

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    Jie Zhang

    Full Text Available The activity of transforming growth factor-β1 (TGF-β1 is regulated by its conversion from the latent to the active form. We have previously shown that the conversion is at least in part mediated by the cationic-independent mannose 6-phosphate receptor (CI-M6PR, as the CI-M6PR inhibitor, PXS-25 has anti-fibrotic properties in human kidney tubular (HK-2 cells under high glucose conditions. However, its clinical use is limited by low bioavailability. Our aim was to determine the effects of PXS64, a pro-drug of PXS25, in in vitro and in vivo models of renal fibrosis. HK-2 cells were exposed to latent TGFβ1+/- PXS64 for 48 hours. The mRNA and protein levels of pro-fibrotic and pro-inflammatory markers were determined. A 7 day unilateral ureteric obstruction (UUO model was used and the following experimental groups were studied: (i Sham operated, (ii UUO, (iii UUO + telmisartan (iv UUO + PSX64. HK-2 cells exposed to PXS64 reduced TGFβ mediated effects on collagen IV, fibronectin, macrophage chemotactic protein-1 (MCP-1 and phospho-smad2 protein expression, consistent with inhibition of the conversion of latent to active TGF-β1. PXS 64 treated UUO mice had a lower tubulointerstitial fibrosis index, collagen IV and fibronectin protein and mRNA expression when compared to untreated UUO mice. In addition, these animals had lower MCP-1 mRNA expression, reduced inflammarory cell infiltrate, as indicated by fewer CD45, F4/80 positive cells, and reduced phospho-Smad2 protein expression when compared to untreated UUO animals. Our data demonstrates that PSX64 is an effective anti-fibrotic agent by inhibiting the activation of latent TGF-β1.

  14. Effectiveness of interceptive treatment of class III malocclusions with skeletal anchorage: A systematic review and meta-analysis (United States)

    Rodríguez de Guzmán-Barrera, Jorge; Sáez Martínez, Carla; Boronat-Catalá, Montserrat; Montiel-Company, Jose María; Paredes-Gallardo, Vanessa; Gandía-Franco, José Luís; Almerich-Silla, José Manuel; Bellot-Arcís, Carlos


    Recently, new strategies for treating class III malocclusions have appeared. Skeletal anchorage appears to reduce the dentoalveolar effects while maximising the orthopaedic effect in growing patients. The purpose of this systematic review and meta-analysis is to examine the effectiveness of bone anchorage devices for interceptive treatment of skeletal class III malocclusions. Searches were made in the Pubmed, Embase, Scopus and Cochrane databases, as well as in a grey literature database, and were complemented by hand-searching. The criteria for eligibility were: patients who had undergone orthodontic treatment with skeletal anchorage (miniplates and miniscrews). Patients with syndromes or craniofacial deformities or who had undergone maxillofacial surgery were excluded. The following variables were recorded for each article: author, year of publication, type of study, sample size, dropouts, demographic variables, treatment carried out, radiographic study (2D or 3D), follow-up time, and quality of the articles on the Newcastle-Ottawa Scale. The means and confidence intervals of the following variables were employed: Wits, overjet, ANB, SNA and SNB. Initially, 239 articles were identified. After removing the duplicates and applying the selection criteria, 9 were included in the qualitative synthesis and 7 in the quantitative synthesis (meta-analysis). It may be concluded that skeletal anchorage is an effective treatment for improving skeletal Class III malocclusion, but when compared with other traditional treatments such as disjunction and face mask, there is no clear evidence that skeletal anchorage improves the results. PMID:28328995

  15. Impact of a new gasoline benzene regulation on ambient air pollutants in Anchorage, Alaska (United States)

    Yano, Yuriko; Morris, Stephen S.; Salerno, Christopher; Schlapia, Anne M.; Stichick, Mathew


    The purpose of this study was to quantify the impact of a new U.S. Environmental Protection Agency (EPA) standard that limits the amount of benzene allowed in gasoline on ambient benzene concentrations. This new standard, together with two companion regulations that limit cold-temperature automotive emissions and the permeability of portable fuel containers, was expected to lower the levels of ambient benzene and other volatile organic compounds (VOCs) nationwide. In this study the impact of the gasoline benzene standard was evaluated in Anchorage, Alaska in a two-phase ambient air monitoring study conducted before and after the new gasoline standard was implemented. Gasoline sold by Anchorage retailers was also evaluated in each phase to determine the content of benzene and other gasoline components. The average benzene content in Anchorage gasoline was reduced by 70%, from 5.05% (w/w) to 1.53% (w/w) following the implementation of the standard. The annual mean ambient benzene concentration fell by 51%, from 0.99 ppbv in Phase 1 to 0.49 ppbv in Phase 2. Analysis suggests the change in gasoline benzene content alone reduced benzene emissions by 46%. The changes in toluene, ethylbenzene, and xylene content in gasoline between Phase 1 and 2 were relatively small and the differences in the mean ambient concentrations of these compounds between phases were modest. Our results suggest that cold winter communities in high latitude and mountainous regions may benefit more from the gasoline benzene standard because of high benzene emissions resulting from vehicle cold start and a tendency to develop atmospheric stagnation conditions in the winter.

  16. Dental Extrusion with Orthodontic Miniscrew Anchorage: A Case Report Describing a Modified Method

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    Ricardo Fidos Horliana


    Full Text Available In recent years, the skeletal anchorage through miniscrews has expanded the treatment options in orthodontics (Yamaguchi et al., 2012. We hereby present a modified method for tooth extrusion for cases where crown-lengthening surgery is contraindicated for aesthetic reasons. This modified method uses three orthodontic appliances: a mini-implant, an orthodontic wire, and a bracket. The aim of this case report was to increase the length of the clinical crown of a fractured tooth (tooth 23 by means of an orthodontic extrusion with the modified method of Roth and Diedrich.

  17. Randomized clinical trial comparing control of maxillary anchorage with 2 retraction techniques. (United States)

    Xu, Tian-Min; Zhang, Xiaoyun; Oh, Hee Soo; Boyd, Robert L; Korn, Edward L; Baumrind, Sheldon


    The objective of this pilot randomized clinical trial was to investigate the relative effectiveness of anchorage conservation of en-masse and 2-step retraction techniques during maximum anchorage treatment in patients with Angle Class I and Class II malocclusions. Sixty-four growing subjects (25 boys, 39 girls; 10.2-15.9 years old) who required maximum anchorage were randomized to 2 treatment techniques: en-masse retraction (n = 32) and 2-step retraction (n = 32); the groups were stratified by sex and starting age. Each patient was treated by a full-time clinic instructor experienced in the use of both retraction techniques at the orthodontic clinic of Peking University School of Stomatology in China. All patients used headgear, and most had transpalatal appliances. Lateral cephalograms taken before treatment and at the end of treatment were used to evaluate treatment-associated changes. Differences in maxillary molar mesial displacement and maxillary incisor retraction were measured with the before and after treatment tracings superimposed on the anatomic best fit of the palatal structures. Differences in mesial displacement of the maxillary first molar were compared between the 2 treatment techniques, between sexes, and between different starting-age groups. Average mesial displacement of the maxillary first molar was slightly less in the en-masse group than in the 2-step group (mean, -0.36 mm; 95% CI, -1.42 to 0.71 mm). The average mesial displacement of the maxillary first molar for both treatment groups pooled (n = 63, because 1 patient was lost to follow-up) was 4.3 ± 2.1 mm (mean ± standard deviation). Boys had significantly more mesial displacement than girls (mean difference, 1.3 mm; P <0.03). Younger adolescents had significantly more mesial displacement than older adolescents (mean difference, 1.3 mm; P <0.02). Average mesial displacement of the maxillary first molar with 2-step retraction was slightly greater than that for en-masse retraction, but the

  18. Moving singularity creep crack growth analysis with the /Delta T/c and C/asterisk/ integrals. [path-independent vector and energy rate line integrals (United States)

    Stonesifer, R. B.; Atluri, S. N.


    The physical meaning of (Delta T)c and its applicability to creep crack growth are reviewed. Numerical evaluation of (Delta T)c and C(asterisk) is discussed with results being given for compact specimen and strip geometries. A moving crack-tip singularity, creep crack growth simulation procedure is described and demonstrated. The results of several crack growth simulation analyses indicate that creep crack growth in 304 stainless steel occurs under essentially steady-state conditions. Based on this result, a simple methodology for predicting creep crack growth behavior is summarized.

  19. Independent Directors

    DEFF Research Database (Denmark)

    Ringe, Wolf-Georg


    This paper re-evaluates the corporate governance concept of ‘board independence’ against the disappointing experiences during the 2007-08 financial crisis. Independent or outside directors had long been seen as an essential tool to improve the monitoring role of the board. Yet the crisis revealed...... that they did not prevent firms' excessive risk taking; further, these directors sometimes showed serious deficits in understanding the business they were supposed to control, and remained passive in addressing structural problems. A closer look reveals that under the surface of seemingly unanimous consensus...... about board independence in Western jurisdictions, a surprising disharmony prevails about the justification, extent and purpose of independence requirements. These considerations lead me to question the benefits of the current system. Instead, this paper proposes a new, ‘functional’ concept of board...

  20. 17 beta-estradiol-BSA conjugates and 17 beta-estradiol regulate growth plate chondrocytes by common membrane associated mechanisms involving PKC dependent and independent signal transduction. (United States)

    Sylvia, V L; Walton, J; Lopez, D; Dean, D D; Boyan, B D; Schwartz, Z


    Nuclear receptors for 17 beta-estradiol (E(2)) are present in growth plate chondrocytes from both male and female rats and regulation of chondrocytes through these receptors has been studied for many years; however, recent studies indicate that an alternative pathway involving a membrane receptor may also be involved in the cell response. E(2) was found to directly affect the fluidity of chondrocyte membranes derived from female, but not male, rats. In addition, E(2) activates protein kinase C (PKC) in a nongenomic manner in female cells, and chelerythrine, a specific inhibitor of PKC, inhibits E(2)-dependent alkaline phosphatase activity and proteoglycan sulfation in these cells, indicating PKC is involved in the signal transduction mechanism. The aims of the present study were: (1) to examine the effect of a cell membrane-impermeable 17 beta-estradiol-bovine serum albumin conjugate (E(2)-BSA) on chondrocyte proliferation, differentiation, and matrix synthesis; (2) to determine the pathway that mediates the membrane effect of E(2)-BSA on PKC; and (3) to compare the action of E(2)-BSA to that of E(2). Confluent, fourth passage resting zone (RC) and growth zone (GC) chondrocytes from female rat costochondral cartilage were treated with 10(-9) to 10(-7) M E(2) or E(2)-BSA and changes in alkaline phosphatase specific activity, proteoglycan sulfation, and [(3)H]-thymidine incorporation measured. To examine the pathway of PKC activation, chondrocyte cultures were treated with E(2)-BSA in the presence or absence of GDP beta S (inhibitor of G-proteins), GTP gamma S (activator of G-proteins), U73122 or D609 (inhibitors of phospholipase C [PLC]), wortmannin (inhibitor of phospholipase D [PLD]) or LY294002 (inhibitor of phosphatidylinositol 3-kinase). E(2)-BSA mimicked the effects of E(2) on alkaline phosphatase specific activity and proteoglycan sulfation, causing dose-dependent increases in both RC and GC cell cultures. Both forms of estradiol inhibited [(3)H

  1. Outcomes and stability in patients with anterior open bite and long anterior face height treated with temporary anchorage devices and a maxillary intrusion splint (United States)

    Scheffler, Nicole R.; Proffit, William R.; Phillips, Ceib


    Introduction Temporary skeletal anchorage devices now offer the possibility of closing anterior open bites and decreasing anterior face height by intruding maxillary posterior teeth, but data for treatment outcomes are lacking. This article presents outcomes and posttreatment changes for consecutive patients treated with a standardized technique. Methods The sample included 33 consecutive patients who had intrusion of maxillary posterior teeth with a maxillary occlusal splint and nickel-titanium coil springs to temporary anchorage devices in the zygomatic buttress area, buccal and apical to the maxillary molars. Of this group, 30 had adequate cephalograms available for the period of treatment, 27 had cephalograms including 1-year posttreatment, and 25 had cephalograms from 2 years or longer. Results During splint therapy, the mean molar intrusion was 2.3 mm. The mean decrease in anterior face height was 1.6 mm, less than expected because of a 0.6-mm mean eruption of the mandibular molars. During the postintrusion orthodontics, the mean change in maxillary molar position was a 0.2-mm extrusion, and there was a mean 0.5-mm increase in face height. Positive overbite was maintained in all patients, with a slight elongation (<2 mm) of the incisors contributing to this. During the 1 year of posttreatment retention, the mean changes were a further eruption of 0.5 mm of the maxillary molars, whereas the mandibular molars intruded by 0.6 mm, and there was a small decrease in anterior face height. Changes beyond 1 year posttreatment were small and attributable to growth rather than relapse in tooth positions. Conclusions Intrusion of the maxillary posterior teeth can give satisfactory correction of moderately severe anterior open bites, but 0.5 to 1.5 mm of reeruption of these teeth is likely to occur. Controlling the vertical position of the mandibular molars so that they do not erupt as the maxillary teeth are intruded is important in obtaining a decrease in face height

  2. Behaviour of plate anchorage in plate-reinforced composite coupling beams. (United States)

    Lam, W Y; Li, Lingzhi; Su, R K L; Pam, H J


    As a new alternative design, plate-reinforced composite (PRC) coupling beam achieves enhanced strength and ductility by embedding a vertical steel plate into a conventionally reinforced concrete (RC) coupling beam. Based on a nonlinear finite element model developed in the authors' previous study, a parametric study presented in this paper has been carried out to investigate the influence of several key parameters on the overall performance of PRC coupling beams. The effects of steel plate geometry, span-to-depth ratio of beams, and steel reinforcement ratios at beam spans and in wall regions are quantified. It is found that the anchorage length of the steel plate is primarily controlled by the span-to-depth ratio of the beam. Based on the numerical results, a design curve is proposed for determining the anchorage length of the steel plate. The load-carrying capacity of short PRC coupling beams with high steel ratio is found to be controlled by the steel ratio of wall piers. The maximum shear stress of PRC coupling beams should be limited to 15 MPa.

  3. Prestressed CFRP Strips with Gradient Anchorage for Structural Concrete Retrofitting: Experiments and Numerical Modeling

    Directory of Open Access Journals (Sweden)

    Julien Michels


    Full Text Available This paper presents a study on the load carrying capacity of reinforced concrete (RC beams strengthened with externally bonded (EB carbon fiber reinforced polymer (CFRP strips prestressed up to 0.6% in strain. At the strip ends, the innovative gradient anchorage is used instead of conventional mechanical fasteners. This method, based on the epoxy resin’s ability to rapidly cure under high temperatures, foresees a sector-wise heating followed by a gradual decrease of the initial prestress force towards the strip ends. The experimental investigation shows a promising structural behavior, resulting in high strip tensile strains, eventually almost reaching tensile failure of the composite strip. Additionally, ductility when considering deflection at steel yielding and at ultimate load is satisfying, too. From a practical point of view, it is demonstrated that premature strip grinding in the anchorage zone is not beneficial. In addition, a non-commercial 1D finite element code has been enlarged to an EB reinforcement with prestressed composite strips. A bilinear bond stress-slip relation obtained in earlier investigations is introduced as an additional failure criterion to the code. The numerical code is able to almost perfectly predict the overall structural behavior. Furthermore, the calculations are used for comparison purposes between an initially unstressed and a prestressed externally bonded composite reinforcement. The increase in cracking and yielding load, as well as differences in structural stiffness are apparent.

  4. Skeletal anchorage for orthodontic correction of severe maxillary protrusion after previous orthodontic treatment. (United States)

    Tanaka, Eiji; Nishi-Sasaki, Akiko; Hasegawa, Takuro; Nishio, Clarice; Kawai, Nobuhiko; Tanne, Kazuo


    The correction of a severe maxillary protrusion in an adult by distal movement of the maxillary molars has been one of the most difficult biomechanical problems in orthodontics. This article reports on the treatment of an adult case of severe maxillary protrusion and a large overjet treated with a skeletal anchorage system. A female patient, age 22 years and 3 months, complained of the difficulty of lip closure due to severe maxillary protrusion with a gummy smile. Overjet and overbite were +7.6 mm and -0.9 mm, respectively. She had a history of orthodontic treatment in which her maxillary first premolars were extracted. In order to conduct distal movement of the maxillary molars, anchor plates were placed in the zygomatic process. After achieving a Class I molar relationship, retraction and intrusion of the maxillary incisors were performed. After a 2-year treatment, an acceptable occlusion was achieved with a Class I molar relationship. Her convex facial profile with upper lip protrusion was considerably improved, and the lips showed less tension in lip closure. After a 2-year retention period, an acceptable occlusion was maintained without recurrence of maxillary protrusion, indicating a stability of the occlusion. The result of this treatment indicated that skeletal anchorage is of great importance as a remedy for achieving intrusion and retraction of the maxillary incisors in cases of severe maxillary protrusion with a patient who had previous orthodontic treatment.

  5. Modified Miniplates for Temporary Skeletal Anchorage in Orthodontics: Placement and Removal Surgeries (United States)

    Cornelis, Marie A.; Scheffler, Nicole R.; Mahy, Pierre; Siciliano, Sergio; De Clerck, Hugo J.; Tulloch, J.F. Camilla


    Purpose Skeletal anchorage systems are increasingly used in orthodontics. This article describes the techniques of placement and removal of modified surgical miniplates used for temporary orthodontic anchorage and reports surgeons’ perceptions of their use. Patients and Methods We enrolled 97 consecutive orthodontic patients having miniplates placed as an adjunct to treatment. A total of 200 miniplates were placed by 9 oral surgeons. Patients and surgeons completed questionnaires after placement and removal surgeries. Results Fifteen miniplates needed to be removed prematurely. Antibiotics and anti-inflammatories were generally prescribed after placement but not after removal surgery. Most surgeries were performed with the patient under local anesthesia. Placement surgery lasted on average between 15 and 30 minutes per plate and was considered by the surgeons to be very easy to moderately easy. The surgery to remove the miniplates was considered easier and took less time. The patients’ chief complaint was swelling, lasting on average 5.3 ± 2.8 days after placement and 4.5 ± 2.6 days after removal. Conclusions Although miniplate placement/removal surgery requires the elevation of a flap, this was considered an easy and relatively short surgical procedure that can typically be performed with the patient under local anesthesia without complications, and it may be considered a safe and effective adjunct for orthodontic treatment. PMID:18571028

  6. Patients’ and orthodontists’ perceptions of miniplates used for temporary skeletal anchorage: A prospective study (United States)

    Cornelis, Marie A.; Scheffler, Nicole R.; Nyssen-Behets, Catherine; De Clerck, Hugo J.; Tulloch, J. F. Camilla


    Introduction Temporary skeletal anchorage is a relatively recent addition to orthodontic treatment. Surgical miniplates, modified with intraoral attachments, provide an alternative to miniscrews for skeletal anchorage. In this study, we wanted to determine patients’ and providers’ perceptions of miniplate use during orthodontic treatment. Methods Consecutive patients having miniplates placed as part of their treatment completed questionnaires about their experiences during surgery and orthodontic treatment. A total of 200 miniplates were placed for 97 patients. The 30 orthodontists treating these patients also completed questionnaires concerning miniplate success, handling complexity, and whether these devices simplified treatment. Results The success rate was 92.5%. The devices were well tolerated by the patients. After a year, 72% of the patients reported that they did not mind having the implant, and 82% said that the surgical experience was better than expected, with little or no pain. The most frequent problems were postsurgical swelling, lasting 5 days on average, and cheek irritation experienced initially by more than a third of the patients, but it lessened over time. The clinicians reported that these devices were easy to use and greatly simplified orthodontic treatment. Conclusions Miniplates are well accepted by patients and providers and are a safe and effective adjunct for complex orthodontic treatments. PMID:18174066

  7. Growth of triple-negative breast cancer cells relies upon coordinate autocrine expression of the proinflammatory cytokines IL-6 and IL-8. (United States)

    Hartman, Zachary C; Poage, Graham M; den Hollander, Petra; Tsimelzon, Anna; Hill, Jamal; Panupinthu, Nattapon; Zhang, Yun; Mazumdar, Abhijit; Hilsenbeck, Susan G; Mills, Gordon B; Brown, Powel H


    Triple-negative breast cancers (TNBC) are aggressive with no effective targeted therapies. A combined database analysis identified 32 inflammation-related genes differentially expressed in TNBCs and 10 proved critical for anchorage-independent growth. In TNBC cells, an LPA-LPAR2-EZH2 NF-κB signaling cascade was essential for expression of interleukin (IL)-6, IL-8, and CXCL1. Concurrent inhibition of IL-6 and IL-8 expression dramatically inhibited colony formation and cell survival in vitro and stanched tumor engraftment and growth in vivo. A Cox multivariable analysis of patient specimens revealed that IL-6 and IL-8 expression predicted patient survival times. Together these findings offer a rationale for dual inhibition of IL-6/IL-8 signaling as a therapeutic strategy to improve outcomes for patients with TNBCs.

  8. Choosing Independence

    Institute of Scientific and Technical Information of China (English)


    Milo Djukanovic, Prime Minister of Montenegro, won a key referendum May 21 when voters in his tiny, mountainous nation endorsed a plan to split from Serbia and become an independent state. This marked a final step in the breakup of the former Yugoslavia formed by six republics.

  9. The pRB-related protein p107 contains two growth suppression domains : independent interactions with E2F and cyclin/cdk complexes

    NARCIS (Netherlands)

    Zhu, L.; Enders, G.; Lees, J.A.; Beijersbergen, R.L.; Bernards, R.A.; Harlow, E.


    Unregulated expression of either the retinoblastoma protein (pRB) or the related protein p107 can cause growth arrest of sensitive cells in the G1 phase of the cell cycle. However, growth arrests mediated by p107 and pRB are not identical. Through structure-function and co-expression analyses we hav

  10. Independent preferences

    DEFF Research Database (Denmark)

    Vind, Karl


    A simple mathematical result characterizing a subset of a product set is proved and used to obtain additive representations of preferences. The additivity consequences of independence assumptions are obtained for preferences which are not total or transitive. This means that most of the economic...... theory based on additive preferences - expected utility, discounted utility - has been generalized to preferences which are not total or transitive. Other economic applications of the theorem are given...

  11. Lin28 promotes growth of prostate cancer cells and activates the androgen receptor. (United States)

    Tummala, Ramakumar; Nadiminty, Nagalakshmi; Lou, Wei; Zhu, Yezi; Gandour-Edwards, Regina; Chen, Hong-Wu; Evans, Christopher P; Gao, Allen C


    Prostate cancer (CaP) progresses to a castration-resistant state assisted by multifold molecular changes, most of which involve activation of the androgen receptor (AR). Having previously demonstrated the importance of the Lin28/let-7/Myc axis in CaP, we tested the hypothesis that Lin28 is overexpressed in CaP and that it activates AR and promotes growth of CaP cells. We analyzed human clinical CaP samples for the expression of Lin28 by quantitative real-time RT-PCR, Western blot analysis, and IHC. Growth characteristics of CaP cell lines transiently and stably expressing Lin28 were examined. The clonogenic ability of CaP cells expressing Lin28 was determined by colony formation and soft agar assays. Increase in expression of AR and subsequent increase in transcription of AR-target genes were analyzed by quantitative real-time RT-PCR, luciferase assays, and ELISA. LNCaP cells stably expressing Lin28 were injected into nude mice, and tumorigenesis was monitored. We found that Lin28 is overexpressed in clinical CaP compared to benign prostates. Overexpression of Lin28 enhanced, while down-regulation reduced, growth of CaP cells. Lin28 enhanced the ability of CaP cells to form colonies in anchorage-dependent and anchorage-independent conditions. LNCaP cells stably expressing Lin28 exhibited significantly higher tumorigenic ability in vivo. Lin28 induced expression of the AR and its target genes such as PSA and NKX3.1. Collectively, our findings demonstrate a novel role for Lin28 in CaP development and activation of the AR axis. Copyright © 2013 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  12. The flexible evolutionary anchorage-dependent Pardee's restriction point of mammalian cells: how its deregulation may lead to cancer. (United States)

    David-Pfeuty, Thérèse


    , because of their innate flexibility, anchorage-dependent R points have also the ability to readily adjust to a changing structural context so as to give mutated cells a chance to reproduce, thereby encouraging tumor genesis. The Rb and p53 proteins, which are regulated by the two products of the Ink4a-Arf locus [C.J. Sherr, The INK4a/ARF network in tumor suppression, Nat. Rev., Mol. Cell Biol. 2 (2001) 731-737], govern separable though interconnected pathways that cooperate to restrain cyclin D- and cyclin E-dependent kinases from precipitating untimely R point transit. The expression levels of the Ink4a and Arf proteins are especially sensitive to changes in cellular shape and adhesion that entirely remodel at the time when cells shift between quiescence and division. The Arf proteins further display an extremely high translational sensitivity and can activate the p53 pathway to delay R point transit, but, only when released from the nucleolus, 'an organelle formed by the act of building a ribosome' [T. Mélèse, Z. Xue, The nucleolus: an organelle formed by the act of building a ribosome, Curr. Opin. Cell Biol. 7 (1995) 319-324]. In this way, the Ink4a/Rb and Arf/p53 pathways emerge as key regulators of anchorage-dependent R point transit in mammalian cells and their deregulation is, indeed, a rule in human cancers. Thus, by selecting the nucleolus to mitigate cell cycle control by the Arf proteins, mammalian cells succeeded in forging a highly flexible R point enabling them to match cell division with a growth rate imposed by factors controlling nucleolar assembling, such as nutrients and adhesion. It is noteworthy that nutrient control of critical size at Start in budding yeast has been shown recently to be governed by a nucleolar protein interaction network [P. Jorgensen, J.L. Nishikawa, B.-J. Breitkreutz, M. Tyers, Systematic identification of pathways that couple cell growth and division in yeast, Science 297 (2002) 395-400].

  13. Catecholamine-stimulated Growth of Aeromonas hydrophila Requires the TonB2 Energy Transduction System but is Independent of the Amonabactin Siderophore

    Directory of Open Access Journals (Sweden)

    Yuhao Dong


    Full Text Available The growth-stimulating effects of catecholamine stress hormones have been demonstrated in many pathogens. However, catecholamine-induced growth and its underlying mechanisms remain poorly understood in Aeromonas hydrophila. The present study sought to demonstrate that norepinephrine (NE, epinephrine (Epi, dopamine (Dopa and L-dopa stimulate the growth of A. hydrophila in iron-restricted media containing serum. NE exhibited the strongest growth stimulation, which could be blocked by adrenergic antagonists. Furthermore, it was demonstrated that NE could sequester iron from transferrin, thereby providing a more accessible iron source for utilization by A. hydrophila. The deletion of the amoA gene associated with amonabactin synthesis revealed that the amonabactin siderophore is not required for NE-stimulated growth. However, the deletion of the TonB2 energy transduction system resulted in the loss of growth promotion by NE, indicating that a specific TonB-dependent outer membrane receptor might be involved in the transport of iron from transferrin. Collectively, our data show that catecholamine sensing promotes the growth of A. hydrophila in a manner that is dependent on the TonB2 energy transduction system.

  14. Catecholamine-Stimulated Growth of Aeromonas hydrophila Requires the TonB2 Energy Transduction System but Is Independent of the Amonabactin Siderophore (United States)

    Dong, Yuhao; Liu, Jin; Pang, Maoda; Du, Hechao; Wang, Nannan; Awan, Furqan; Lu, Chengping; Liu, Yongjie


    The growth-stimulating effects of catecholamine stress hormones have been demonstrated in many pathogens. However, catecholamine-induced growth and its underlying mechanisms remain poorly understood in Aeromonas hydrophila. The present study sought to demonstrate that norepinephrine (NE), epinephrine (Epi), dopamine (Dopa), and L-dopa stimulate the growth of A. hydrophila in iron-restricted media containing serum. NE exhibited the strongest growth stimulation, which could be blocked by adrenergic antagonists. Furthermore, it was demonstrated that NE could sequester iron from transferrin, thereby providing a more accessible iron source for utilization by A. hydrophila. The deletion of the amoA gene associated with amonabactin synthesis revealed that the amonabactin siderophore is not required for NE-stimulated growth. However, the deletion of the TonB2 energy transduction system resulted in the loss of growth promotion by NE, indicating that a specific TonB-dependent outer membrane receptor might be involved in the transport of iron from transferrin. Collectively, our data show that catecholamine sensing promotes the growth of A. hydrophila in a manner that is dependent on the TonB2 energy transduction system. PMID:28018865

  15. Gas Source MBE Growth and Characterization of TlInGaAs/InP DH Structures for Temperature-independent Wavelength LD Application (United States)


    UNCLASSIFIED Defense Technical Information Center Compilation Part Notice ADP012655 TITLE: Gas Source MBE Growth and Characterization of TlInGaAs/InP...UNCLASSIFIED Mat. Res. Soc. Symp. Proc. Vol. 692 © 2002 Materials Research Society H9.27 Gas Source MBE Growth and Characterization of TlInGaAs/InP DH...electroluminescence (EL) properties for the TlInGaAs/InP light emitting diodes (LEDs) are also described. GAS SOURCE MBE GROWTH TlInGaAs/lnP DH structures were grown

  16. 33 CFR 165.110 - Safety and Security Zone; Liquefied Natural Gas Carrier Transits and Anchorage Operations, Boston... (United States)


    ...; Liquefied Natural Gas Carrier Transits and Anchorage Operations, Boston, Massachusetts. 165.110 Section 165... Limited Access Areas First Coast Guard District § 165.110 Safety and Security Zone; Liquefied Natural Gas... ahead and one mile astern, and 500 yards on each side of any liquefied natural gas carrier (LNGC)...

  17. A mixed-methods approach for analysing social support and social anchorage of single mothers’ personal networks

    NARCIS (Netherlands)

    Lumino, Rosaria; Ragozini, Giancarlo; van Duijn, Marijtje; Vitale, Maria Prosperina


    The present paper analyses the relationship among social support and personal networks by focusing on social anchorage, which is a specific dimension of social support conveying to what extent people feel integrated into their personal networks. Specifying when, why, and how personal relationships

  18. 77 FR 66942 - Anchorages; Lower Mississippi River, Above Head of Passes, Convent, LA and Point Pleasant, LA (United States)


    ... INFORMATION section below for instructions on submitting comments. To avoid duplication, please use only one... anchored or moored within the anchorage areas. D. Regulatory Analyses We developed this proposed rule after... Homeland Security Management Directive 023-01 and Commandant Instruction M16475.lD, which guide the...

  19. The "Real Self" and Inauthenticity: The Importance of Self-Concept Anchorage for Emotional Experiences in the Workplace (United States)

    Sloan, Melissa M.


    I examine the utility of self-concept anchorage (as described by Turner 1976) in the analysis of inauthenticity in the workplace. As controlling internally felt emotion may distance the worker from her true feelings or true self, the management of emotion in the workplace can produce feelings of inauthenticity in the worker. This relationship has…

  20. Nanoparticulate mineralized collagen scaffolds induce in vivo bone regeneration independent of progenitor cell loading or exogenous growth factor stimulation. (United States)

    Ren, Xiaoyan; Tu, Victor; Bischoff, David; Weisgerber, Daniel W; Lewis, Michael S; Yamaguchi, Dean T; Miller, Timothy A; Harley, Brendan A C; Lee, Justine C


    Current strategies for skeletal regeneration often require co-delivery of scaffold technologies, growth factors, and cellular material. However, isolation and expansion of stem cells can be time consuming, costly, and requires an additional procedure for harvest. Further, the introduction of supraphysiologic doses of growth factors may result in untoward clinical side effects, warranting pursuit of alternative methods for stimulating osteogenesis. In this work, we describe a nanoparticulate mineralized collagen glycosaminoglycan scaffold that induces healing of critical-sized rabbit cranial defects without addition of expanded stem cells or exogenous growth factors. We demonstrate that the mechanism of osteogenic induction corresponds to an increase in canonical BMP receptor signalling secondary to autogenous production of BMP-2 and -9 early and BMP-4 later during differentiation. Thus, nanoparticulate mineralized collagen glycosaminoglycan scaffolds may provide a novel growth factor-free and ex vivo progenitor cell culture-free implantable method for bone regeneration.

  1. Mechanisms of Glioma Formation: Iterative Perivascular Glioma Growth and Invasion Leads to Tumor Progression, VEGF-Independent Vascularization, and Resistance to Antiangiogenic Therapy

    Directory of Open Access Journals (Sweden)

    Gregory J. Baker


    Full Text Available As glioma cells infiltrate the brain they become associated with various microanatomic brain structures such as blood vessels, white matter tracts, and brain parenchyma. How these distinct invasion patterns coordinate tumor growth and influence clinical outcomes remain poorly understood. We have investigated how perivascular growth affects glioma growth patterning and response to antiangiogenic therapy within the highly vascularized brain. Orthotopically implanted rodent and human glioma cells are shown to commonly invade and proliferate within brain perivascular space. This form of brain tumor growth and invasion is also shown to characterize de novo generated endogenous mouse brain tumors, biopsies of primary human glioblastoma (GBM, and peripheral cancer metastasis to the human brain. Perivascularly invading brain tumors become vascularized by normal brain microvessels as individual glioma cells use perivascular space as a conduit for tumor invasion. Agent-based computational modeling recapitulated biological perivascular glioma growth without the need for neoangiogenesis. We tested the requirement for neoangiogenesis in perivascular glioma by treating animals with angiogenesis inhibitors bevacizumab and DC101. These inhibitors induced the expected vessel normalization, yet failed to reduce tumor growth or improve survival of mice bearing orthotopic or endogenous gliomas while exacerbating brain tumor invasion. Our results provide compelling experimental evidence in support of the recently described failure of clinically used antiangiogenics to extend the overall survival of human GBM patients.

  2. Orthodontic retreatment using anchorage with miniplate to camouflage a Class III skeletal pattern

    Directory of Open Access Journals (Sweden)

    Marcel Marchiori Farret

    Full Text Available ABSTRACT This manuscript describes the treatment of a 27-year-old patient who was previously treated with two maxillary first premolar extractions. The patient had skeletal Class III malocclusion, Class III canine relationship, anterior crossbite, and a concave profile. As the patient refused orthognathic surgery, a miniplate was used on the right side of the lower arch as an anchorage unit after the extraction of mandibular first premolars, aiding the retraction of anterior teeth. At the end of treatment, anterior crossbite was corrected, in which first molars and canines were in a Class I relationship, and an excellent intercuspation was reached. Furthermore, patient's profile remarkably improved as a result of mandibular incisor retraction. A 30-month follow-up showed good stability of the results obtained. This case was presented to the Brazilian Board of Orthodontics and Dentofacial Orthopedics (BBO as one of the requirements to become diplomate by the BBO.

  3. Elmendorf AFB, Anchorage, Alaska. Revised Uniform Summary of Surface Weather Observations (RUSSWO). Parts A-F (United States)


    OBSERVATIONS) 260 EjJMENDORF AF0 ALASK /ANCHORAGE 6 6-79 SE ITATION STATION RAMP VEA~sS 505Thm CALL WIATivg 2800-2000 CLA" 40 isA IS EL..) ( CONDItION SPEED) 1...iiiiiiii - - _ l-l nA T A ,1, 1C. is Z’I e(’ ,It .,. - DAILY TEMPERATURES l if ?,52 4C: I L;I1.,-JuIqkI AF, ALA.aVA/Al C1-I!R1t .; ,| ’,i 5 -/ iSA ,;O...2 0. O 3,861.7 .550 8/5 . 1 1 2 14 101 Element (X) ZX9 Z X I Mean No. of Hours w th Temp rtu re < RJh 4418271 60855 69.9 87 870 . F 󈧤F 67F 73F 80F

  4. Orthodontic retreatment using anchorage with miniplate to camouflage a Class III skeletal pattern (United States)

    Farret, Marcel Marchiori


    ABSTRACT This manuscript describes the treatment of a 27-year-old patient who was previously treated with two maxillary first premolar extractions. The patient had skeletal Class III malocclusion, Class III canine relationship, anterior crossbite, and a concave profile. As the patient refused orthognathic surgery, a miniplate was used on the right side of the lower arch as an anchorage unit after the extraction of mandibular first premolars, aiding the retraction of anterior teeth. At the end of treatment, anterior crossbite was corrected, in which first molars and canines were in a Class I relationship, and an excellent intercuspation was reached. Furthermore, patient's profile remarkably improved as a result of mandibular incisor retraction. A 30-month follow-up showed good stability of the results obtained. This case was presented to the Brazilian Board of Orthodontics and Dentofacial Orthopedics (BBO) as one of the requirements to become diplomate by the BBO. PMID:27409659

  5. [Treatment of adult bimaxillary arch protrusion with micro-implant anchorage]. (United States)

    Chen, Cheng; Zhang, Xiao-Rong


    In this study, micro-implants were used in 15 adult patients with mild and moderate bimaxillary arch protrusion or crowding. Cephalometric analysis was used to analyze hard and soft-tissues change before and after treatment, with the aim to investigate the effects of treatment on adult bimaxillary arch protrusion with micro-implant anchorage. Fifteen adult patients with mild and moderate bimaxillary arch protrusion were selected in this study. Micro-implants were inserted into the zygomaticoalveolar ridge of maxilla and the external oblique line of mandible. A NiTi coil spring was attached to the micro-implant to drag the whole upper and lower dentition for distal movement. Cephalometrics were taken before and after treatment, and the changes of soft and hard-tissue profile were studied. SPSS13.0 software package was used to analyze the data. (1)Sixty micro-implants remained stable.(2)SNA, SNB had no significant changes (P>0.05), and the relationship between the maxilla and the mandible did not change significantly. U1/NA, U1-NA, L1/NB, L1-NB and U1/L1 changes in hard tissue had significant difference in cephalometric measurement (P<0.05). The upper and lower anterior teeth were more retrusive, and the tipping of incisor decreased significantly.(3)Cephalometric analysis showed that lateral appearance improved and soft tissue cephalometric-related measurements such as Cm-Sn-UL,LL-B'-Pos increased significantly (P<0.01). (4)Molars and incisors acquired distal movement. Micro-implant can provide not only excellent skeletal anchorage but also a novel way to distalize the whole dentition efficiently.

  6. Pomegranate Juice Metabolites, Ellagic Acid and Urolithin A, Synergistically Inhibit Androgen-Independent Prostate Cancer Cell Growth via Distinct Effects on Cell Cycle Control and Apoptosis


    Roberto Vicinanza; Yanjun Zhang; Susanne M Henning; David Heber


    Ellagitannins (ETs) from pomegranate juice (PJ) are bioactive polyphenols with chemopreventive potential against prostate cancer (PCa). ETs are not absorbed intact but are partially hydrolyzed in the gut to ellagic acid (EA). Colonic microflora can convert EA to urolithin A (UA), and EA and UA enter the circulation after PJ consumption. Here, we studied the effects of EA and UA on cell proliferation, cell cycle, and apoptosis in DU-145 and PC-3 androgen-independent PCa cells and whether combi...

  7. Plasma connective tissue growth factor is an independent predictor of end-stage renal disease and mortality in type 1 diabetic nephropathy

    DEFF Research Database (Denmark)

    Nguyen, T.Q.; Tarnow, L.; Jorsal, A.


    OBJECTIVE: We evaluated the predictive value of baseline plasma connective tissue growth factor (CTGF) in a prospective study of patients with type 1 diabetes. RESEARCH DESIGN AND METHODS: Subjects were 198 type 1 diabetic patients with established diabetic nephropathy and 188 type 1 diabetic...

  8. Plasma connective tissue growth factor is an independent predictor of end-stage renal disease and mortality in type 1 diabetic nephropathy.

    NARCIS (Netherlands)

    Nguyen, T.Q.; Tarnow, L.; Jorsal, A.; Oliver, N.; Roestenberg, P.M.H.; Ito, Y.; Parving, H.H.; Rossing, P.; Nieuwenhoven, FA van; Goldschmeding, R.


    OBJECTIVE: We evaluated the predictive value of baseline plasma connective tissue growth factor (CTGF) in a prospective study of patients with type 1 diabetes. RESEARCH DESIGN AND METHODS: Subjects were 198 type 1 diabetic patients with established diabetic nephropathy and 188 type 1 diabetic patien

  9. An integrin binding-defective mutant of insulin-like growth factor-1 (R36E/R37E IGF1) acts as a dominant-negative antagonist of the IGF1 receptor (IGF1R) and suppresses tumorigenesis but still binds to IGF1R. (United States)

    Fujita, Masaaki; Ieguchi, Katsuaki; Cedano-Prieto, Dora M; Fong, Andrew; Wilkerson, Charles; Chen, Jane Q; Wu, Mac; Lo, Su-Hao; Cheung, Anthony T W; Wilson, Machelle D; Cardiff, Robert D; Borowsky, Alexander D; Takada, Yoko K; Takada, Yoshikazu


    Insulin-like growth factor-1 (IGF1) is a major therapeutic target for cancer. We recently reported that IGF1 directly binds to integrins (αvβ3 and α6β4) and induces ternary complex formation (integrin-IGF1-IGF1 receptor (IGF1R)) and that the integrin binding-defective mutant of IGF1 (R36E/R37E) is defective in signaling and ternary complex formation. These findings predict that R36E/R37E competes with WT IGF1 for binding to IGF1R and inhibits IGF signaling. Here, we described that excess R36E/R37E suppressed cell viability increased by WT IGF1 in vitro in non-transformed cells. We studied the effect of R36E/R37E on viability and tumorigenesis in cancer cell lines. We did not detect an effect of WT IGF1 or R36E/R37E in cancer cells under anchorage-dependent conditions. However, under anchorage-independent conditions, WT IGF1 enhanced cell viability and induced signals, whereas R36E/R37E did not. Notably, excess R36E/R37E suppressed cell viability and signaling induced by WT IGF1 under anchorage-independent conditions. Using cancer cells stably expressing WT IGF1 or R36E/R37E, we determined that R36E/R37E suppressed tumorigenesis in vivo, whereas WT IGF1 markedly enhanced it. R36E/R37E suppressed the binding of WT IGF1 to the cell surface and the subsequent ternary complex formation induced by WT IGF1. R36E/R37E suppressed activation of IGF1R by insulin. WT IGF1, but not R36E/R37E, induced ternary complex formation with the IGF1R/insulin receptor hybrid. These findings suggest that 1) IGF1 induces signals under anchorage-independent conditions and that 2) R36E/R37E acts as a dominant-negative inhibitor of IGF1R (IGF1 decoy). Our results are consistent with a model in which ternary complex formation is critical for IGF signaling.

  10. Arachidonic acid alters tomato HMG expression and fruit growth and induces 3-hydroxy-3-methylglutaryl coenzyme A reductase-independent lycopene accumulation

    Energy Technology Data Exchange (ETDEWEB)

    Rodriguez-Concepcion, M.; Gruissem, W. [Univ. of California, Berkeley, CA (United States). Dept. of Plant and Microbial Biology


    Regulation of isoprenoid end-product synthesis required for normal growth and development in plants is not well understood. To investigate the extent to which specific genes for the enzyme 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR) are involved in end-product regulation, the authors manipulated expression of the HMG1 and HMG2 genes in tomato (Lycopersicon esculentum) fruit using arachidonic acid (AA). In developing young fruit AA blocked fruit growth, inhibited HMG1, and activated HMG2 expression. These results are consistent with other reports indicating that HMG1 expression is closely correlated with growth processes requiring phytosterol production. In mature-green fruit AA strongly induced the expression of HMG2, PSY1 (the gene for phytoene synthase), and lycopene accumulation before the normal onset of carotenoid synthesis and ripening. The induction of lycopene synthesis was not blocked by inhibition of HMGR activity using mevinolin, suggesting that cytoplasmic HMGR is not required for carotenoid synthesis. Their results are consistent with the function of an alternative plastid isoprenoid pathway (the Rohmer pathway) that appears to direct the production of carotenoids during tomato fruit ripening.

  11. Bio-cultural anchorage of the prickly pear cactus in Tlalnepantla (Morelos, Mexico

    Directory of Open Access Journals (Sweden)

    Torres-Salcido, Gerardo


    Full Text Available The prickly pear cactus is a source of food with strong bio-cultural anchorage in Mexico. This is due to at least three factors: 1 the nature and heritage of cacti; 2 cultural heritage; and 3 the socio-cultural relationships with historical and symbolic roots that have facilitated knowledge of how to cultivate it and how to use it. The aim of this article is to put factors of territorial anchorage and its historical transformation in context by examining the case of the municipality of Tlalnepantla in the state of Morelos, Mexico. This community has experienced accelerated change due to the exchange of traditional crops for the prickly pear cactus and the integration of farming, commercialization and agro-transformation. Our hypothesis is that the market, internal conflicts and a lack of socio-institutional coordination have put social organization into crisis, favoring the territorial spread of the prickly pear cactus and making the Local Agro-Food Systems (LAFS of Tlalnepantla less competitive. The conclusions highlight important economic and social advances whose roots lie in the strengthening and anchorage of the territory-product. However, circumstances both internal and external to the community persist, such as intra-community conflicts, the international market and cultural paradigm shifts that affect the producers and put consolidation of the LAFS at risk.El nopal es un alimento con un fuerte anclaje bio-cultural en México, propiciado por al menos tres factores: 1 la naturaleza y el patrimonio de cactáceas; 2 el patrimonio cultural; y, 3 las relaciones socio-culturales que han permitido un “saber hacer” y un “saber utilizar” con raíces históricas y simbólicas. El objetivo es situar los factores de anclaje territorial y su transformación histórica tomando como caso el municipio de Tlalnepantla, en el estado de Morelos, México. Esta comunidad ha experimentado un acelerado cambio por la reconversión de los cultivos

  12. Culture-dependent and culture-independent assessment of spoilage community growth on VP lamb meat from packaging to past end of shelf-life. (United States)

    Kaur, Mandeep; Shang, Hongshan; Tamplin, Mark; Ross, Tom; Bowman, John P


    Packaging and storage temperature are important factors that influence the shelf-life of vacuum packed (VP) meat. In this study the shelf-life of VP bone-in lamb hind shanks stored at 8 °C and -1.2 °C was determined in parallel to analyses of starting and eventual spoilage bacterial communities via Illumina MiSeq based 16S rRNA amplicon sequencing. The mean total viable counts (TVC) and lactic acid bacterial viable counts (LAB) were observed to increase to log 7.5 CFU/cm(2) and 7 CFU/cm(2) after 6 and 42 days at 8 °C and -1.2 °C and stayed stable until shelf-life termination after 13 and 124 days, respectively. The sequence data showed initial communities were patchily distributed and were mainly derived from skin microbiome taxa likely prevalent within the abattoir. A broad diversity of VP meat associated specific spoilage organisms (SSO) were comparatively abundant in this initial population. Overtime meat spoilage communities developed a distinctive and stable microbiome. At -1.2 °C SSO included mainly Carnobacterium, Yersinia and Clostridium spp. while at 8 °C SSO expanded to include Hafnia, Lactococcus, Providencia spp. Growth curves inferred from the sequence data after taking into account rRNA copy number suggested that SSO growth rates were consistent with overall growth rates determined from TVC and LAB data and are predictable. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

  13. Postnatal liver growth and regeneration are independent of c-myc in a mouse model of conditional hepatic c-myc deletion

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    Sanders Jennifer A


    Full Text Available Abstract Background The transcription factor c-myc regulates genes involved in hepatocyte growth, proliferation, metabolism, and differentiation. It has also been assigned roles in liver development and regeneration. In previous studies, we made the unexpected observation that c-Myc protein levels were similar in proliferating fetal liver and quiescent adult liver with c-Myc displaying nucleolar localization in the latter. In order to investigate the functional role of c-Myc in adult liver, we have developed a hepatocyte-specific c-myc knockout mouse, c-mycfl/fl;Alb-Cre. Results Liver weight to body weight ratios were similar in control and c-myc deficient mice. Liver architecture was unaffected. Conditional c-myc deletion did not result in compensatory induction of other myc family members or in c-Myc's binding partner Max. Floxed c-myc did have a negative effect on Alb-Cre expression at 4 weeks of age. To explore this relationship further, we used the Rosa26 reporter line to assay Cre activity in the c-myc floxed mice. No significant difference in Alb-Cre activity was found between control and c-mycfl/fl mice. c-myc deficient mice were studied in a nonproliferative model of liver growth, fasting for 48 hr followed by a 24 hr refeeding period. Fasting resulted in a decrease in liver mass and liver protein, both of which recovered upon 24 h of refeeding in the c-mycfl/fl;Alb-Cre animals. There was also no effect of reducing c-myc on recovery of liver mass following 2/3 partial hepatectomy. Conclusions c-Myc appears to be dispensable for normal liver growth during the postnatal period, restoration of liver mass following partial hepatectomy and recovery from fasting.

  14. Mitogen-activated protein kinase 4 is a salicylic acid-independent regulator of growth but not of photosynthesis in Arabidopsis. (United States)

    Gawroński, Piotr; Witoń, Damian; Vashutina, Kateryna; Bederska, Magdalena; Betliński, Błażej; Rusaczonek, Anna; Karpiński, Stanisław


    Mitogen-activated protein kinase (MAPK) pathways regulate signal transduction from different cellular compartments and from the extracellular environment to the nucleus in all eukaryotes. One of the best-characterized MAPKs in Arabidopsis thaliana is MPK4, which was shown to be a negative regulator of systemic-acquired resistance. The mpk4 mutant accumulates salicylic acid (SA), possesses constitutive expression of pathogenesis-related (PR) genes, and has an extremely dwarf phenotype. We show that suppression of SA and phylloquinone synthesis in chloroplasts by knocking down the ICS1 gene (by crossing it with the ics1 mutant) in the mpk4 mutant background did not revert mpk4-impaired growth. However, it did cause changes in the photosynthetic apparatus and severely impaired the quantum yield of photosystem II. Transmission microscopy analysis revealed that the chloroplasts' structure was strongly altered in the mpk4 and mpk4/ics1 double mutant. Analysis of reactive oxygen species (ROS)-scavenging enzymes expression showed that suppression of SA and phylloquinone synthesis in the chloroplasts of the mpk4 mutant caused imbalances in ROS homeostasis which were more pronounced in mpk4/ics1 than in mpk4. Taken together, the presented results strongly suggest that MPK4 is an ROS/hormonal rheostat hub that negatively, in an SA-dependent manner, regulates immune defenses, but at the same time positively regulates photosynthesis, ROS metabolism, and growth. Therefore, we concluded that MPK4 is a complex regulator of chloroplastic retrograde signaling for photosynthesis, growth, and immune defenses in Arabidopsis.

  15. Transdisciplinary treatment of Class III malocclusion using conventional implant-supported anchorage: 10-year posttreatment follow-up

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    Mariana Roennau Lemos Rinaldi


    Full Text Available INTRODUCTION: Combined treatment offers advantages for partially edentulous patients. Conventional implants, used as orthodontic anchorage, enable previous orthodontic movement, which provides appropriate space gain for crown insertion. OBJECTIVE: This case report describes the treatment of a 61-year and 10-month-old patient with negative overjet which made ideal prosthetic rehabilitation impossible, thereby hindering dental and facial esthetics. CASE REPORT: After a diagnostic setup, conventional implants were placed in the upper arch to anchor intrusion and retract anterior teeth. Space gain for lateral incisors was achieved in the lower arch by means of an orthodontic appliance. CONCLUSIONS: Integrated planning combining Orthodontics and Implantology provided successful treatment by means of conventional implant-supported anchorage. The resulting occlusal relationship proved stable after 10 years.

  16. The U.S. Department of Energy Office of Indian Energy Policy and Programs, Anchorage, Alaska, Roundtable Summary

    Energy Technology Data Exchange (ETDEWEB)



    The Anchorage, Alaska Roundtable on Tribal Energy Policy convened at 10:00 a.m., Thursday April 15th, at the downtown Anchorage Hilton. The meeting was held by the Department of Energy (DOE) Office of Indian Energy Policy and Programs (Office of Indian Energy). Tracey LeBeau, Director of the Office of Indian Energy, and Pilar Thomas, Deputy Director-Policy of the Office of Indian Energy, represented DOE. Approximately twenty-seven people attended the meeting, including representatives of three native Alaskan villages, four Alaskan tribal corporations representing more than 40 tribal governments, as well as representatives from tribal associations and conferences. Interested state, federal, and non-profit representatives also were present. A full list of attendees is at the end of this summary. The meeting was facilitated by the Udall Foundation’s U.S. Institute for Environmental Conflict Resolution (U.S. Institute).  

  17. Metallurgical Behavior of Ti-6Al-4V Alloy Mini-Implants as a Temporary Anchorage Device in Orthodontics Applications

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    Mendoza-Bravo Ivan


    Full Text Available The application of mini implants as a temporary anchorage device in orthodontics is a new technique that allows the movement of teeth in an efficient and predictable way. Although they have started to be used in Germany, Japan and South Korea, there is still the need to analyze and diffuse the advantages this procedure can offer over the traditional techniques. The objective of this research work was to analyze the integrity of Ti-6Al-4V mini implants temporary employed for 4 months on three patients as an anchorage device. The mini implants were analyzed by means of electron scanning microscopy in order to determine superficial and microstructural changes as well as the interaction with human tissue. Results showed the presence of wear on the thread zone caused during the insertion into the maxilar bone. The adherence of organic tissue was also observed on two mini-implants.

  18. Latest Pleistocene advance and collapse of the Matanuska - Knik glacier system, Anchorage Lowland, southern Alaska (United States)

    Kopczynski, Sarah E.; Kelley, Samuel E.; Lowell, Thomas V.; Evenson, Edward B.; Applegate, Patrick J.


    At the end of the last ice age, glacier systems worldwide underwent dramatic retreat. Here, we document the advance and retreat of a glacier system with adjacent marine- and land-based components during the latter part of the Termination. We utilize three lines of evidence: lithologic provenance, geomorphic mapping, and radiocarbon ages derived from lake cores to reconstruct glacier extent and timing of advance and retreat within our study area centered at N 61.50°, W 149.50°, just north of Anchorage, Alaska. Two glaciers, sourced in the Talkeetna and Chugach Mountains, flowed down the Matanuska and Knik Valleys forming a coalesced lobe that advanced onto the Anchorage Lowlands and terminated at Elmendorf Moraine. We use the presence of lithologies unique to the Matanuska catchment in glacial drift to delineate the paleoflow lines and to estimate the suture line of the two glacier systems. The eastern side of the lobe, attributed to ice flow from the Knik Valley, was in contact with elevated marine waters within the Knik Arm fjord, and thus retreat was likely dominated by calving. Geomorphic evidence suggests the western side of the lobe, attributed to ice flow from Matanuska Valley, retreated due to stagnation. We constrain retreat of the combined Matanuska and Knik lobe with thirteen new radiocarbon ages, in addition to previously published radiocarbon ages, and with geomorphic evidence suggesting the retreat occurred in two phases. Retreat from the Elmendorf Moraine began between 16.8 and 16.4 ka BP. A second, faster retreat phase occurred later and was completed by 13.7 ka BP. With the 140 km of total retreat occurring over ∼3000 years or less. This pattern of glacial advance and retreats agrees well with the deglacial histories from the southern sectors of the Cordilleran Ice Sheet, as well as many other alpine glacier systems in the western U.S. and northern Alaska. This consistent behavior of glacier systems may indicate that climate oscillated over

  19. [Biomechanical effect of 2 anchorages on maxillary protraction with cleft lip and palate: a finite element analysis]. (United States)

    Han, Han; Xu, Ya-Fen; Duan, Yu-Feng; Lei, Yong-Hua


    To establish cranio-maxillary complex finite element models (FEMs) in cleft lip and palate (CLP) patients with miniplate and tooth-borne anchorage, and to investigate the biomechanical effects on maxillary protraction. The protracting process was simulated on FEMs established from a male patient's cone beam CT (CBCT) data to analyze the displacement and stress from different appliances. Four FEMs of unilateral cleft lip and palate (UCLP) or bilateral cleft lip and palate (BCLP) patients' cranio-maxillary complex with MA and TA were established. The maxillary arch on both sides of the cleft moved towards the cleft side during protraction, which was more obvious in the miniplate anchorage three-dimensional finite element models(FEM-MA) than the tooth-borne anchorage three-dimensional finite element models (FEM-TA).The amount of forward, downward displacement of the inferior orbital rim, paranasal area and middle maxilla point in the FEM-MA was larger than that in the FEM-TA, while the amount of forward displacement of premaxilla and upper canine in the FEM-TA was larger than that in the FEM-MA. The FEM-MA exhibited an orthopedic effect with more favorable stress distribution on the middle maxilla point while the FEM-TA showed a dentoalveolar effect with prominent stress distribution on the upper canine point. In addition, the FEM-MA showed a larger stress distribution area and sutural stress value than did the FEM-TA. The UCLP models showed an asymmetric pattern in stress distribution and displacement, which was larger on the cleft side than that on the non-cleft side. The amount of displacement of premaxilla in the BCLP models was smaller than that in the UCLP models. The established models have high geomagic and biomechanical similarities. It would be more advantageous to obtain more aesthetic outcomes and better stability using the miniplate anchorage.

  20. Effects of Growth Phase and Temperature on σB Activity within a Listeria monocytogenes Population: Evidence for RsbV-Independent Activation of σB at Refrigeration Temperatures

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    Marta Utratna


    Full Text Available The alternative sigma factor σB of Listeria monocytogenes is responsible for regulating the transcription of many of the genes necessary for adaptation to both food-related stresses and to conditions found within the gastrointestinal tract of the host. The present study sought to investigate the influence of growth phase and temperature on the activation of σB within populations of L. monocytogenes EGD-e wild-type, ΔsigB, and ΔrsbV throughout growth at both 4°C and 37°C, using a reporter fusion that couples expression of EGFP to the strongly σB-dependent promoter of lmo2230. A similar σB activation pattern within the population was observed in wt-egfp at both temperatures, with the highest induction of σB occurring in the early exponential phase of growth when the fluorescent population rapidly increased, eventually reaching the maximum in early stationary phase. Interestingly, induction of σB activity was heterogeneous, with only a proportion of the cells in the wt-egfp population being fluorescent above the background autofluorescence level. Moreover, significant RsbV-independent activation of σB was observed during growth at 4°C. This result suggests that an alternative route to σB activation exists in the absence of RsbV, a finding that is not explained by the current model for σB regulation.

  1. Human Sarcoma growth is sensitive to small-molecule mediated AXIN stabilization.

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    Alessandra De Robertis

    Full Text Available Sarcomas are mesenchymal tumors showing high molecular heterogeneity, reflected at the histological level by the existence of more than fifty different subtypes. Genetic and epigenetic evidences link aberrant activation of the Wnt signaling to growth and progression of human sarcomas. This phenomenon, mainly accomplished by autocrine loop activity, is sustained by gene amplification, over-expression of Wnt ligands and co-receptors or epigenetic silencing of endogenous Wnt antagonists. We previously showed that pharmacological inhibition of Wnt signaling mediated by Axin stabilization produced in vitro and in vivo antitumor activity in glioblastoma tumors. Here, we report that targeting different sarcoma cell lines with the Wnt inhibitor/Axin stabilizer SEN461 produces a less transformed phenotype, as supported by modulation of anchorage-independent growth in vitro. At the molecular level, SEN461 treatment enhanced the stability of the scaffold protein Axin1, a key negative regulator of the Wnt signaling with tumor suppressor function, resulting in downstream effects coherent with inhibition of canonical Wnt signaling. Genetic phenocopy of small molecule Axin stabilization, through Axin1 over-expression, coherently resulted in strong impairment of soft-agar growth. Importantly, sarcoma growth inhibition through pharmacological Axin stabilization was also observed in a xenograft model in vivo in female CD-1 nude mice. Our findings suggest the usefulness of Wnt inhibitors with Axin stabilization activity as a potentialyl clinical relevant strategy for certain types of sarcomas.

  2. Neurotensin, a novel target of Wnt/β-catenin pathway, promotes growth of neuroendocrine tumor cells. (United States)

    Kim, Ji Tae; Liu, Chunming; Zaytseva, Yekaterina Y; Weiss, Heidi L; Townsend, Courtney M; Evers, B Mark


    Wnt/β-catenin signaling plays a pivotal role in regulating cell growth and differentiation by activation of the β-catenin/T-cell factor (TCF) complex and subsequent regulation of a set of target genes that have one or more TCF-binding elements (TBEs). Hyperactivation of this pathway has been implicated in numerous malignancies including human neuroendocrine tumors (NETs). Neurotensin (NT), an intestinal hormone, induces proliferation of several gastrointestinal (GI) cancers including cancers of the pancreas and colon. Here, we analyzed the human NT promoter in silico and found at least four consensus TBEs within the proximal promoter region. Using a combination of ChIP and luciferase reporter assays, we identified one TBE (located ∼900 bp proximal from the transcription start site) that was immunoprecipitated efficiently by TCF4-targeting antibody; mutation of this site attenuated the responsiveness to β-catenin. We also confirmed that the promoter activity and the mRNA and protein expression levels of NT were increased by various Wnt pathway activators and decreased by Wnt inhibitors in NET cell lines BON and QGP-1, which express and secrete NT. Similarly, the intracellular content and secretion of NT were induced by Wnt3a in these cells. Finally, inhibition of NT signaling suppressed cell proliferation and anchorage-independent growth and decreased expression levels of growth-related proteins in NET cells. Our results indicate that NT is a direct target of the Wnt/β-catenin pathway and may be a mediator for NET cell growth.

  3. The Effects of Pre-feeding Oral Stimulations and Non-nutritive Sucking on Physical Growth and Independent Oral Feeding of Preterm Infants

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    Nasrin Khalessi


    Full Text Available Background: Breastfeeding failures and oral feeding problems in preterm infants result in long-term health complications. In this study, therefore, we aimed to evaluate the effect of oral stimulation along with non-nutritive sucking (NNS on independent oral feeding initiation and weight gain in preterm infants. Methods: This prospective randomized clinical trial was carried out at Aliasghar Hospital in Tehran, Iran, 2014. A total of 50 26-32 weeks gestational age hospitalized infants, who were fed through tubes, were recruited in the study. The newborns were randomized into A, B and C groups. In the A and B groups, the neonates were stimulated through oral stimulation as well as non-nutritive sucking for 5 or 10 days, while in the group C, no especial intervention was performed. Infants' mean daily weight gain, the number of days until initiation of oral feeding, oral feeding progression, the number of days until reaching full oral feeding and date of discharge were recorded. The obtained data were analyzed and compared in the three groups using SPSS version 16.0. Results: Of all the participants, 25 cases (55.55% were male. Mean gestational age at birth and mean birth weight were 28.64±1.93 weeks and 1337.11±185.07 grams, respectively. In the group A, newborns' weight at reaching four and eight oral feedings per day and their weights at discharge were significantly higher than the other two groups (P=0.016, 0.001 and 0.001, respectively. Mean daily weight gain in the group A was higher (84.2850 g than the other groups (69.5814 vs. 64.2677 g. However, ANOVA results showed that this difference was not significant (P=0.108. Moreover, independent samples t-test indicated that this difference between groups A and C was significant (P=0.049. Conclusion: In clinically stable preterm neonates, oral stimulation and should be implemented to increase their weight; however, further studies are required to address this issue.

  4. Pomegranate Juice Metabolites, Ellagic Acid and Urolithin A, Synergistically Inhibit Androgen-Independent Prostate Cancer Cell Growth via Distinct Effects on Cell Cycle Control and Apoptosis

    Directory of Open Access Journals (Sweden)

    Roberto Vicinanza


    Full Text Available Ellagitannins (ETs from pomegranate juice (PJ are bioactive polyphenols with chemopreventive potential against prostate cancer (PCa. ETs are not absorbed intact but are partially hydrolyzed in the gut to ellagic acid (EA. Colonic microflora can convert EA to urolithin A (UA, and EA and UA enter the circulation after PJ consumption. Here, we studied the effects of EA and UA on cell proliferation, cell cycle, and apoptosis in DU-145 and PC-3 androgen-independent PCa cells and whether combinations of EA and UA affected cell proliferation. EA demonstrated greater dose-dependent antiproliferative effects in both cell lines compared to UA. EA induced cell cycle arrest in S phase associated with decreased cyclin B1 and cyclin D1 levels. UA induced a G2/M arrest and increased cyclin B1 and cdc2 phosphorylation at tyrosine-15, suggesting inactivation of the cyclin B1/cdc2 kinase complex. EA induced apoptosis in both cell lines, while UA had a less pronounced proapoptotic effect only in DU-145. Cotreatment with low concentrations of EA and UA dramatically decreased cell proliferation, exhibiting synergism in PC-3 cells evaluated by isobolographic analysis and combination index. These data provide information on pomegranate metabolites for the prevention of PCa recurrence, supporting the role of gut flora-derived metabolites for cancer prevention.

  5. Pomegranate Juice Metabolites, Ellagic Acid and Urolithin A, Synergistically Inhibit Androgen-Independent Prostate Cancer Cell Growth via Distinct Effects on Cell Cycle Control and Apoptosis. (United States)

    Vicinanza, Roberto; Zhang, Yanjun; Henning, Susanne M; Heber, David


    Ellagitannins (ETs) from pomegranate juice (PJ) are bioactive polyphenols with chemopreventive potential against prostate cancer (PCa). ETs are not absorbed intact but are partially hydrolyzed in the gut to ellagic acid (EA). Colonic microflora can convert EA to urolithin A (UA), and EA and UA enter the circulation after PJ consumption. Here, we studied the effects of EA and UA on cell proliferation, cell cycle, and apoptosis in DU-145 and PC-3 androgen-independent PCa cells and whether combinations of EA and UA affected cell proliferation. EA demonstrated greater dose-dependent antiproliferative effects in both cell lines compared to UA. EA induced cell cycle arrest in S phase associated with decreased cyclin B1 and cyclin D1 levels. UA induced a G2/M arrest and increased cyclin B1 and cdc2 phosphorylation at tyrosine-15, suggesting inactivation of the cyclin B1/cdc2 kinase complex. EA induced apoptosis in both cell lines, while UA had a less pronounced proapoptotic effect only in DU-145. Cotreatment with low concentrations of EA and UA dramatically decreased cell proliferation, exhibiting synergism in PC-3 cells evaluated by isobolographic analysis and combination index. These data provide information on pomegranate metabolites for the prevention of PCa recurrence, supporting the role of gut flora-derived metabolites for cancer prevention.

  6. Liquid marbles for high-throughput biological screening of anchorage-dependent cells. (United States)

    Oliveira, Nuno M; Correia, Clara R; Reis, Rui L; Mano, João F


    Stable liquid marbles (LM) are produced by coating liquid droplets with a hydrophobic powder. The used hydrophobic powder is produced by fluorosi-lanization of diatomaceous earth, used before to produce superhydrophobic structures. Here, the use of LM is proposed for high-throughput drug screening on anchorage-dependent cells. To provide the required cell adhesion sites inside the liquid environment of LM, surface-modified poly(l-lactic acid) microparticles are used. A simple method that takes advantage from LM appealing features is presented, such as the ability to inject liquid on LM without disrupting (self-healing ability), and to monitor color changes inside of LM. After promoting cell adhesion, a cytotoxic screening test is performed as a proof of concept. Fe(3+) is used as a model cytotoxic agent and is injected on LM. After incubation, AlamarBlue reagent is injected and used to assess the presence of viable cells, by monitoring color change from blue to red. Color intensity is measured by image processing and the analysis of pictures takes using an ordinary digital camera. The proposed method is fully validated in counterpoint to an MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carbo​xymethoxyphenyl)-2-(4-sulfophenyl)-2H-te​trazolium) colorimetric assay, a well-known method used for the cytotoxicity assessment.

  7. Oral and dental restoration of wide alveolar cleft using distraction osteogenesis and temporary anchorage devices. (United States)

    Rachmiel, Adi; Emodi, Omri; Gutmacher, Zvi; Blumenfeld, Israel; Aizenbud, Dror


    Closure of large alveolar clefts and restoration by a fixed bridge supported by implants is a challenge in cleft alveolus treatment. A major aesthetic concern with distraction osteogenesis is obtaining a predictable position of the implant in relation to the newly generated bony alveolar ridge. We describe the treatment of a large cleft alveolus and palate reconstruction by distraction osteogenesis utilizing temporary anchorage devices (TADs) followed by a fixed implant-supported bridge. The method consists of segmental bone transport by distraction osteogenesis using a bone-borne distractor to minimize the alveolar cleft, followed by closure of the residual small defect by bone grafting three months later. During the active transport distraction, TADs were used exerting multidirectional forces to control the distraction vector forward and laterally for better interarch relation. A vertical alveolar distraction of the newly reconstructed bone of 15 mm facilitated optimal implant placement. The endosseous implants were osteointegrated and supported a fixed dental prosthesis. In conclusion, the large cleft alveolus defect was repaired in three dimensions by distraction osteogenesis assisted by TADs, and the soft tissues expanded simultaneously. Endosseous implants were introduced in the newly reconstructed bone for a fixed dental prosthesis enabling, rehabilitation of aesthetics, eating and speaking.

  8. The perception of pain following interdental microimplant treatment for skeletal anchorage: a retrospective study. (United States)

    Chen, Chun-Ming; Chang, Chao-San; Tseng, Yu-Chuan; Hsu, Kun-Rong; Lee, Kun-Tsung; Lee, Huey-Er


    During orthodontic therapy, patients frequently complain about pain and discomfort, especially during insertion of fixed appliances. Skeletal anchorage using an interdental microimplant is a new concept in orthodontic treatment. The purpose of this study was to investigate differences and changes in the level of pain among patients in relation to orthodontic microimplant treatments. Forty microimplants were applied to the maxilla as skeletal anchors in the orthodontic treatment. The visual analog scale (VAS) was used to evaluate the patients' perception of pain during this new modality treatment. The premolar extraction VAS core was used as a baseline for the complete orthodontic procedure. The mean VAS score was 35.8 mm at 24 h after premolar extraction. The mean VAS score for insertion and removal of the microimplant 24 h after the operation was 12.3 and 7.8 mm, respectively. Three months after removal of the skeletal anchors, the VAS score had decreased to 3.2 mm and was the same as with the traditional orthodontic treatment. By using the repeated-measure general linear model (GLM), we found that the score 1 day after microimplant placement was significantly less than that 1 day after first premolar extraction or that 1 day after fixed appliance insertion. This result indicates that interdental microimplant did not generate any greater pain than other orthodontic procedures. Therefore, patients were willing to adopt the new orthodontic treatment.

  9. Biomechanical comparison of four different miniscrew types for skeletal anchorage in the mandibulo-maxillary area. (United States)

    Mischkowski, R A; Kneuertz, P; Florvaag, B; Lazar, F; Koebke, J; Zöller, J E


    This study compared four miniscrew types for skeletal anchorage (Aarhus, FAMI, Dual Top and Spider) regarding their biomechanical properties contributing to primary stability. Insertion torque measurements and pull-out tests in axial (0 degrees ) as well as in the 20 degrees and 40 degrees direction were performed. Stiffness of the screw-bone construct was calculated from the load-displacement curve. Conic FAMI and Dual Top screws had higher insertion torques. Insertion torques were raised by drill-free insertion of FAMI and Dual Top screws. Statistically significant differences were found between the 4 screw types in pull-out tests. The highly significant differences between the four screws for peak load in the axial (0 degrees ) and 20 degrees direction were not apparent in 40 degrees angular loads. For the conical screws, peak load values increased in angular compared with axial load. The Dual Top screw achieved the highest values for peak load and stiffness. 12 Dual Top and 1 Spider screw heads fractured in the pull-out tests. A conical drill-free screw design achieves higher primary stability compared with cylindrical self-tapping screws. This effect was more obvious in insertion torque estimations rather than in pull-out tests. The Dual Top screws, although biomechanically superior to other screw types, were most prone to fractures.

  10. The variable anchorage straight wire technique compared with the straight wire technique in deep overbite correction. (United States)

    Banaie, Fariba; Parikakis, Konstantinos; Moberg, Svante; Hellsing, Eva


    The aim of this retrospective study was to compare the treatment results and the number of required treatment appointments between the variable anchorage straight wire technique (VAST) and the straight wire (SW) technique. The subjects were 53 Caucasian patients of both sexes (25 males and 28 females, mean age 13.5 years at the start of treatment), with an overjet > or = 4 mm and an overbite > or = 3 mm. The patients were divided into four groups, VAST (n = 31) or SW (n = 22), extraction or non-extraction, and were treated by the same orthodontist. Variables from two lateral cephalograms obtained before and at the completion of active treatment, and the number of scheduled appointments were compared between the two techniques. The main difference between the two techniques was the bracket design. With the VAST, the bracket allowed both tipping and parallel movements with the possibility to combine double archwires. Due to the influence of the Begg technique, no extra-oral traction was needed in the VAST groups and Class II elastics were used at the start of treatment. Both techniques seemed to produce equal treatment results. However, in this study, it was shown that in deep overbite correction, the VAST required fewer scheduled appointments than the SW technique.

  11. Treatment effects of the Forsus Fatigue Resistant Device used with miniscrew anchorage. (United States)

    Aslan, Belma I; Kucukkaraca, Ebru; Turkoz, Cagri; Dincer, Mufide


    To evaluate the dentofacial effects of the Forsus Fatigue Resistant Device (FRD) used with miniscrew anchorage (FRDMS) and compare them with those of conventional FRD and an untreated Class II control group. The sample consisted of 48 Class II subjects. Sixteen patients (13.68 ± 1.09 years of age) were treated with FRDMS, whereas 17 subjects (14.64 ± 1.56 years of age) were treated with only FRD. Also, a control sample of 15 untreated Class II subjects (14.13 ± 1.50 years of age) was constructed. Angular and linear measurements were made on 96 lateral cephalograms. Paired t, one-way analysis of variance, and Tukey tests were used for statistical analysis. Class I molar relationship and overjet correction were achieved in an average period of 6.5 ± 1.97 and 5.5 ± 1.80 months in the FRDMS and FRD groups, respectively. No skeletal effect was determined in both treatment groups. Greater overbite correction was found in the FRD group. Retrusion and extrusion of maxillary incisors, distalization of maxillary molars, and extrusion of mandibular molars were significant in both treatment groups. Labial tipping of mandibular incisors was significantly greater in the FRD group than in the FRDMS group. Overjet and molar correction was totally dentoalveolar. Unfavorable labial tipping of mandibular incisors was effectively minimized with the usage of miniscrews.

  12. The Neurofibromatosis 2 Tumor Suppressor Gene Product, Merlin, Regulates Human Meningioma Cell Growth by Signaling through YAP

    Directory of Open Access Journals (Sweden)

    Katherine Striedinger


    Full Text Available Neurofibromatosis type 2 (NF2 is an autosomal dominant disorder characterized by the occurrence of schwannomas and meningiomas. Several studies have examined the ability of the NF2 gene product, merlin, to function as a tumor suppressor in diverse cell types; however, little is known about merlin growth regulation in meningiomas. In Drosophila, merlin controls cell proliferation and apoptosis by signaling through the Hippo pathway to inhibit the function of the transcriptional coactivator Yorkie. The Hippo pathway is conserved in mammals. On the basis of these observations, we developed human meningioma cell lines matched for merlin expression to evaluate merlin growth regulation and investigate the relationship between NF2 status and Yes-associated protein (YAP, the mammalian homolog of Yorkie. NF2 loss in meningioma cells was associated with loss of contact-dependent growth inhibition, enhanced anchorage-independent growth and increased cell proliferation due to increased S-phase entry. In addition, merlin loss in both meningioma cell lines and primary tumors resulted in increased YAP expression and nuclear localization. Finally, siRNA-mediated reduction of YAP in NF2-deficient meningioma cells rescued the effects of merlin loss on cell proliferation and S-phase entry. Collectively, these results represent the first demonstration that merlin regulates cell growth in human cancer cells by suppressing YAP.

  13. Proteasomal degradation of sphingosine kinase 1 and inhibition of dihydroceramide desaturase by the sphingosine kinase inhibitors, SKi or ABC294640, induces growth arrest in androgen-independent LNCaP-AI prostate cancer cells. (United States)

    McNaughton, Melissa; Pitman, Melissa; Pitson, Stuart M; Pyne, Nigel J; Pyne, Susan


    Sphingosine kinases (two isoforms termed SK1 and SK2) catalyse the formation of the bioactive lipid sphingosine 1-phosphate. We demonstrate here that the SK2 inhibitor, ABC294640 (3-(4-chlorophenyl)-adamantane-1-carboxylic acid (pyridin-4-ylmethyl)amide) or the SK1/SK2 inhibitor, SKi (2-(p-hydroxyanilino)-4-(p-chlorophenyl)thiazole)) induce the proteasomal degradation of SK1a (Mr = 42 kDa) and inhibit DNA synthesis in androgen-independent LNCaP-AI prostate cancer cells. These effects are recapitulated by the dihydroceramide desaturase (Des1) inhibitor, fenretinide. Moreover, SKi or ABC294640 reduce Des1 activity in Jurkat cells and ABC294640 induces the proteasomal degradation of Des1 (Mr = 38 kDa) in LNCaP-AI prostate cancer cells. Furthermore, SKi or ABC294640 or fenretinide increase the expression of the senescence markers, p53 and p21 in LNCaP-AI prostate cancer cells. The siRNA knockdown of SK1 or SK2 failed to increase p53 and p21 expression, but the former did reduce DNA synthesis in LNCaP-AI prostate cancer cells. Moreover, N-acetylcysteine (reactive oxygen species scavenger) blocked the SK inhibitor-induced increase in p21 and p53 expression but had no effect on the proteasomal degradation of SK1a. In addition, siRNA knockdown of Des1 increased p53 expression while a combination of Des1/SK1 siRNA increased the expression of p21. Therefore, Des1 and SK1 participate in regulating LNCaP-AI prostate cancer cell growth and this involves p53/p21-dependent and -independent pathways. Therefore, we propose targeting androgen-independent prostate cancer cells with compounds that affect Des1/SK1 to modulate both de novo and sphingolipid rheostat pathways in order to induce growth arrest.

  14. Histone Deacetylase 3 Coordinates Deacetylase-independent Epigenetic Silencing of Transforming Growth Factor-β1 (TGF-β1) to Orchestrate Second Heart Field Development* (United States)

    Lewandowski, Sara L.; Janardhan, Harish P.; Trivedi, Chinmay M.


    About two-thirds of human congenital heart disease involves second heart field-derived structures. Histone-modifying enzymes, histone deacetylases (HDACs), regulate the epigenome; however, their functions within the second heart field remain elusive. Here we demonstrate that histone deacetylase 3 (HDAC3) orchestrates epigenetic silencing of Tgf-β1, a causative factor in congenital heart disease pathogenesis, in a deacetylase-independent manner to regulate development of second heart field-derived structures. In murine embryos lacking HDAC3 in the second heart field, increased TGF-β1 bioavailability is associated with ascending aortic dilatation, outflow tract malrotation, overriding aorta, double outlet right ventricle, aberrant semilunar valve development, bicuspid aortic valve, ventricular septal defects, and embryonic lethality. Activation of TGF-β signaling causes aberrant endothelial-to-mesenchymal transition and altered extracellular matrix homeostasis in HDAC3-null outflow tracts and semilunar valves, and pharmacological inhibition of TGF-β rescues these defects. HDAC3 recruits components of the PRC2 complex, methyltransferase EZH2, EED, and SUZ12, to the NCOR complex to enrich trimethylation of Lys-27 on histone H3 at the Tgf-β1 regulatory region and thereby maintains epigenetic silencing of Tgf-β1 specifically within the second heart field-derived mesenchyme. Wild-type HDAC3 or catalytically inactive HDAC3 expression rescues aberrant endothelial-to-mesenchymal transition and epigenetic silencing of Tgf-β1 in HDAC3-null outflow tracts and semilunar valves. These findings reveal that epigenetic dysregulation within the second heart field is a predisposing factor for congenital heart disease. PMID:26420484

  15. Histone Deacetylase 3 Coordinates Deacetylase-independent Epigenetic Silencing of Transforming Growth Factor-β1 (TGF-β1) to Orchestrate Second Heart Field Development. (United States)

    Lewandowski, Sara L; Janardhan, Harish P; Trivedi, Chinmay M


    About two-thirds of human congenital heart disease involves second heart field-derived structures. Histone-modifying enzymes, histone deacetylases (HDACs), regulate the epigenome; however, their functions within the second heart field remain elusive. Here we demonstrate that histone deacetylase 3 (HDAC3) orchestrates epigenetic silencing of Tgf-β1, a causative factor in congenital heart disease pathogenesis, in a deacetylase-independent manner to regulate development of second heart field-derived structures. In murine embryos lacking HDAC3 in the second heart field, increased TGF-β1 bioavailability is associated with ascending aortic dilatation, outflow tract malrotation, overriding aorta, double outlet right ventricle, aberrant semilunar valve development, bicuspid aortic valve, ventricular septal defects, and embryonic lethality. Activation of TGF-β signaling causes aberrant endothelial-to-mesenchymal transition and altered extracellular matrix homeostasis in HDAC3-null outflow tracts and semilunar valves, and pharmacological inhibition of TGF-β rescues these defects. HDAC3 recruits components of the PRC2 complex, methyltransferase EZH2, EED, and SUZ12, to the NCOR complex to enrich trimethylation of Lys-27 on histone H3 at the Tgf-β1 regulatory region and thereby maintains epigenetic silencing of Tgf-β1 specifically within the second heart field-derived mesenchyme. Wild-type HDAC3 or catalytically inactive HDAC3 expression rescues aberrant endothelial-to-mesenchymal transition and epigenetic silencing of Tgf-β1 in HDAC3-null outflow tracts and semilunar valves. These findings reveal that epigenetic dysregulation within the second heart field is a predisposing factor for congenital heart disease.

  16. Protein Kinase C alpha (PKCα) dependent signaling mediates endometrial cancer cell growth and tumorigenesis (United States)

    Haughian, James M.; Reno, Elaine M.; Thorne, Alicia M.; Bradford, Andrew P.


    Endometrial cancer is the most common invasive gynecologic malignancy, yet molecular mechanisms and signaling pathways underlying its etiology and pathophysiology remain poorly characterized. We sought to define a functional role for the protein kinase C (PKC) isoform, PKCα, in an established cell model of endometrial adenocarcinoma. Ishikawa cells depleted of PKCα protein grew slower, formed fewer colonies in anchorage-independent growth assays and exhibited impaired xenograft tumor formation in nude mice. Consistent with impaired growth, PKCα knockdown increased levels of the cyclin dependent kinase (CDK) inhibitors p21Cip1/WAF1 (p21) and p27Kip1 (p27). Despite the absence of functional phosphatase and tensin homologue (PTEN) protein in Ishikawa cells, PKCα knockdown reduced Akt phosphorylation at serine 473 and concomitantly inhibited phosphorylation of the Akt target, glycogen synthase kinase-3β (GSK-3β). PKCα knockdown also resulted in decreased basal ERK phosphorylation and attenuated ERK activation following EGF stimulation. p21 and p27 expression was not increased by treatment of Ishikawa cells with ERK and Akt inhibitors, suggesting PKCα regulates CDK expression independently of Akt and ERK. Immunohistochemical analysis of grade 1 endometrioid adenocarcinoma revealed aberrant PKCα expression, with foci of elevated PKCα staining, not observed in normal endometrium. These studies demonstrate a critical role for PKCα signaling in endometrial tumorigenesis by regulating expression of CDK inhibitors p21 and p27 and activation of Akt and ERK dependent proliferative pathways. Thus, targeting PKCα may provide novel therapeutic options in endometrial tumors. PMID:19672862

  17. Cell-free synthesis of functional human epidermal growth factor receptor: Investigation of ligand-independent dimerization in Sf21 microsomal membranes using non-canonical amino acids (United States)

    Quast, Robert B.; Ballion, Biljana; Stech, Marlitt; Sonnabend, Andrei; Varga, Balázs R.; Wüstenhagen, Doreen A.; Kele, Péter; Schiller, Stefan M.; Kubick, Stefan


    Cell-free protein synthesis systems represent versatile tools for the synthesis and modification of human membrane proteins. In particular, eukaryotic cell-free systems provide a promising platform for their structural and functional characterization. Here, we present the cell-free synthesis of functional human epidermal growth factor receptor and its vIII deletion mutant in a microsome-containing system derived from cultured Sf21 cells. We provide evidence for embedment of cell-free synthesized receptors into microsomal membranes and asparagine-linked glycosylation. Using the cricket paralysis virus internal ribosome entry site and a repetitive synthesis approach enrichment of receptors inside the microsomal fractions was facilitated thereby providing analytical amounts of functional protein. Receptor tyrosine kinase activation was demonstrated by monitoring receptor phosphorylation. Furthermore, an orthogonal cell-free translation system that provides the site-directed incorporation of p-azido-L-phenylalanine is characterized and applied to investigate receptor dimerization in the absence of a ligand by photo-affinity cross-linking. Finally, incorporated azides are used to generate stable covalently linked receptor dimers by strain-promoted cycloaddition using a novel linker system. PMID:27670253

  18. Lactaptin induces p53-independent cell death associated with features of apoptosis and autophagy and delays growth of breast cancer cells in mouse xenografts.

    Directory of Open Access Journals (Sweden)

    Olga A Koval

    Full Text Available Lactaptin, the proteolytic fragment of human milk kappa-casein, induces the death of various cultured cancer cells. The mechanisms leading to cell death after lactaptin treatment have not been well characterized. In this study the in vivo and in vitro effects of a recombinant analogue of lactaptin (RL2 were examined. Following treatment with the recombinant analogue of lactaptin strong caspase -3, -7 activation was detected. As a consequence of caspase activation we observed the appearance of a sub-G1 population of cells with subdiploid DNA content. Dynamic changes in the mRNA and protein levels of apoptosis-related genes were estimated. No statistically reliable differences in p53 mRNA level or protein level were found between control and RL2-treated cells. We observed that RL2 constitutively suppressed bcl-2 mRNA expression and down regulated Bcl-2 protein expression in MDA-MB-231 cells. We demonstrated that RL2 penetrates cancer and non-transformed cells. Identification of the cellular targets of the lactaptin analogue revealed that α/β-tubulin and α-actinin-1 were RL2-bound proteins. As the alteration in cellular viability in response to protein stimulus can be realized not only by way of apoptosis but also by autophagy, we examined the implications of autophagy in RL2-dependent cell death. We also found that RL2 treatment induces LC3-processing, which is a hallmark of autophagy. The autophagy inhibitor chloroquine enhanced RL2 cytotoxicity to MDA-MB-231 cells, indicating the pro-survival effect of RL2-dependent autophagy. The antitumour potential of RL2 was investigated in vivo in mouse xenografts bearing MDA-MB-231 cells. We demonstrated that the recombinant analogue of lactaptin significantly suppressed the growth of solid tumours. Our results indicate that lactaptin could be a new molecule for the development of anticancer drugs.

  19. Ganodermanontriol (GDNT) exerts its effect on growth and invasiveness of breast cancer cells through the down-regulation of CDC20 and uPA

    Energy Technology Data Exchange (ETDEWEB)

    Jiang, Jiahua; Jedinak, Andrej [Cancer Research Laboratory, Methodist Research Institute, Indiana University Health, Indianapolis, IN (United States); Sliva, Daniel, E-mail: [Cancer Research Laboratory, Methodist Research Institute, Indiana University Health, Indianapolis, IN (United States); Department of Medicine, School of Medicine, Indiana University, Indianapolis, IN (United States); Indiana University Simon Cancer Center, School of Medicine, Indiana University, Indianapolis, IN (United States)


    Highlights: Black-Right-Pointing-Pointer Ganodermanontriol (GDNT), a Ganoderma mushroom alcohol, inhibits growth of breast cancer cells. Black-Right-Pointing-Pointer CDC20 is over-expressed in tumors but not in the tumor surrounding tissue in breast cancer patients. Black-Right-Pointing-Pointer GDNT inhibits expression of CDC20 in breast cancer cells. Black-Right-Pointing-Pointer GDNT inhibits cell adhesion, cell migration and cell invasion of breast cancer cells. Black-Right-Pointing-Pointer GDNT inhibits secretion of uPA and down-regulates expression of uPAR in breast cancer cells. -- Abstract: Ganoderma lucidum is a medicinal mushroom that has been recognized by Traditional Chinese Medicine (TCM). Although some of the direct anticancer activities are attributed to the presence of triterpenes-ganoderic and lucidenic acids-the activity of other compounds remains elusive. Here we show that ganodermanontriol (GDNT), a Ganoderma alcohol, specifically suppressed proliferation (anchorage-dependent growth) and colony formation (anchorage-independent growth) of highly invasive human breast cancer cells MDA-MB-231. GDNT suppressed expression of the cell cycle regulatory protein CDC20, which is over-expressed in precancerous and breast cancer cells compared to normal mammary epithelial cells. Moreover, we found that CDC20 is over-expressed in tumors when compared to the tissue surrounding the tumor in specimens from breast cancer patients. GDNT also inhibited invasive behavior (cell adhesion, cell migration, and cell invasion) through the suppression of secretion of urokinase-plasminogen activator (uPA) and inhibited expression of uPA receptor. In conclusion, mushroom GDNT is a natural agent that has potential as a therapy for invasive breast cancers.

  20. Enhanced invasion and tumor growth of fibroblast growth factor 8b-overexpressing MCF-7 human breast cancer cells. (United States)

    Ruohola, J K; Viitanen, T P; Valve, E M; Seppänen, J A; Loponen, N T; Keskitalo, J J; Lakkakorpi, P T; Härkönen, P L


    Fibroblast growth factor 8 (FGF-8) is a secreted heparin-binding protein, which has mitogenic and transforming activity. Increased expression of FGF-8 has been found in human breast cancer, and it has a potential autocrine role in its progression. Human FGF-8 is alternatively spliced to generate four protein isoforms (a, b, e, and f). Isoform b has been shown to be the most transforming. In this work, we studied the role of FGF-8b in the growth (in vitro and in vivo) of MCF-7 human breast cancer cells, which proliferate in an estrogen-dependent manner. Constitutive overexpression of FGF-8b in MCF-7 cells down-regulated FGF-8b-binding receptors FGF receptor (FGFR) 1IIIc, FGFR2IIIc, and FGFR4 found to be expressed in these cells. FGF-8b overexpression led to an increase in the anchorage-independent proliferation rate in suspension culture and colony formation in soft agar, when MCF-7 cells were cultured with or without estradiol. FGF-8b also provided an additional growth advantage for cells stimulated with estradiol. In addition, FGF-8b-transfected cells invaded more actively through Matrigel than did control cells. This was possibly due to the increased secretion of matrix metalloproteinase 9. In vivo, FGF-8b-transfected MCF-7 cells formed faster growing tumors than vector-only-transfected cells when xenografted into nude mice. The tumors formed by FGF-8b-transfected cells were more vascular than the tumors formed by vector-only-transfected cells. In conclusion, FGF-8b expression confers a growth advantage to MCF-7 breast carcinoma cells, both in vitro and in vivo. In addition to stimulation of proliferation, this growth advantage probably arises from increased invasion and tumor vascularization induced by FGF-8b. The results suggest that FGF-8b signaling may be an important factor in the regulation of tumorigenesis and progression of human breast cancer.

  1. Research Progress of the Anchorage Control in Orthodontic Treatment%正畸治疗中支抗控制的研究进展

    Institute of Scientific and Technical Information of China (English)

    刘春利; 肖丹娜


    The anchorage control is very important in orthodontic treatment,and good design matters to the success or failure of the treatment.Anchorage control includes two aspects of anchorage strengthening and anchorage saving,which both should be taken into consideration,and joint applied in the process of treat-ment.Effect of orthodontic treatment needs multidimensional performance evaluation,to achieve high quality of treatment,sagittal,vertical,and horizontal control should be done according to patients'vertical bone sur-face type and the type of teeth micromaxillary deformity.Here is to make a review of the common methods to strengthen the anchorage,as well as the emerging of strengthening anchorage design,and the idea of the anchorage saving,and the choices of operational and correctional systems.%正畸治疗中支抗控制至关重要,合理的支抗设计关系到治疗的成败。支抗控制可从支抗加强和支抗节省两方面考虑,并在治疗过程中联合应用。正畸治疗效果需以多维效果评价,为取得优质的治疗效果支抗需根据患者的垂直骨面型、牙颌畸形的类型,在矢状向、垂直向、水平向进行控制。该文就目前常用的加强支抗的方法进行简要概括,同时对新兴加强支抗的设计进行简要总结,并对支抗节省的理念、操作和矫治系统的选择进行综述。

  2. Independent Innovation Is a Must

    Institute of Scientific and Technical Information of China (English)


    The importance of independent innovation has been recognized by the Chinese Government and the public. The 11 th Five-Year Plan (2006-10) sets the enhancement of China's capability of independent innovation and the creation of an innovation-driven growth mode as the national strategy that is required to be integrated into every aspect of society. "Independent innovation" was also a key word in Premier Wen Jiabao's report on government work at the recent session of the National People's Congress, the top ...

  3. Nitrate source indicators in ground water of the Scimitar Subdivision, Peters Creek area, Anchorage, Alaska (United States)

    Wang, Bronwen; Strelakos, Pat M.; Jokela, Brett


    A combination of aqueous chemistry, isotopic measurement, and in situ tracers were used to study the possible nitrate sources, the factors contributing to the spatial distribution of nitrate, and possible septic system influence in the ground water in the Scimitar Subdivision, Municipality of Anchorage, Alaska. Two water types were distinguished on the basis of the major ion chemistry: (1) a calcium sodium carbonate water, which was associated with isotopically heavier boron and with chlorofluorocarbons (CFC's) that were in the range expected from equilibration with the atmosphere (group A water) and (2) a calcium magnesium carbonate water, which was associated with elevated nitrate, chloride, and magnesium concentrations, generally isotopically lighter boron, and CFC's concentrations that were generally in excess of that expected from equilibration with the atmosphere (group B water). Water from wells in group B had nitrate concentrations that were greater than 3 milligrams per liter, whereas those in group A had nitrate concentrations of 0.2 milligram per liter or less. Nitrate does not appear to be undergoing extensive transformation in the ground-water system and behaves as a conservative ion. The major ion chemistry trends and the presence of CFC's in excess of an atmospheric source for group B wells are consistent with waste-water influences. The spatial distribution of the nitrate among wells is likely due to the magnitude of this influence on any given well. Using an expanded data set composed of 16 wells sampled only for nitrate concentration, a significant difference in the static water level relative to bedrock was found. Well water samples with less than 1 milligram per liter nitrate had static water levels within the bedrock, whereas those samples with greater than 1 milligram per liter nitrate had static water levels near or above the top of the bedrock. This observation would be consistent with a conceptual model of a low-nitrate fractured bedrock

  4. Recorded earthquake responses from the integrated seismic monitoring network of the Atwood Building, Anchorage, Alaska (United States)

    Celebi, M.


    An integrated seismic monitoring system with a total of 53 channels of accelerometers is now operating in and at the nearby free-field site of the 20-story steel-framed Atwood Building in highly seismic Anchorage, Alaska. The building has a single-story basement and a reinforced concrete foundation without piles. The monitoring system comprises a 32-channel structural array and a 21-channel site array. Accelerometers are deployed on 10 levels of the building to assess translational, torsional, and rocking motions, interstory drift (displacement) between selected pairs of adjacent floors, and average drift between floors. The site array, located approximately a city block from the building, comprises seven triaxial accelerometers, one at the surface and six in boreholes ranging in depths from 15 to 200 feet (???5-60 meters). The arrays have already recorded low-amplitude shaking responses of the building and the site caused by numerous earthquakes at distances ranging from tens to a couple of hundred kilometers. Data from an earthquake that occurred 186 km away traces the propagation of waves from the deepest borehole to the roof of the building in approximately 0.5 seconds. Fundamental structural frequencies [0.58 Hz (NS) and 0.47 Hz (EW)], low damping percentages (2-4%), mode coupling, and beating effects are identified. The fundamental site frequency at approximately 1.5 Hz is close to the second modal frequencies (1.83 Hz NS and 1.43 EW) of the building, which may cause resonance of the building. Additional earthquakes prove repeatability of these characteristics; however, stronger shaking may alter these conclusions. ?? 2006, Earthquake Engineering Research Institute.

  5. Tongue resting pressure of the tongue anchorage pad in different body positions: a pilot study. (United States)

    Zeng, J; Xu, K; Gao, X; Xu, T


    We designed a modified transpalatal arch (tongue anchorage pad, TAP) to help control the vertical dimension. This study aimed to evaluate its efficiency by measuring the tongue resting pressure at different anteroposterior positions of the TAP in the upright and supine positions and to investigate the effect of changes in body position. Our study recruited 17 volunteers with individual normal occlusion (4 males, 13 females, age 22-33 years). An individualised TAP was designed for each subject. With a miniature sensor (FSS1500NS) installed in the device, we measured the pressure at the level of the distal second premolar (PM2), the first molar (M1) and the second molar (M2) in both the upright and supine positions. Nonparametric analysis was applied with the level of significance set at 0.05. In the upright position, tongue pressures obtained at PM2, M1 and M2 were 183.94, 130.81 and 113.07 Pa, respectively, with the maximum value detected at PM2 (P = 0.001). While in the supine position, pressures of 187.03, 156.87 and 201.69 Pa were detected at the same sites, with significantly higher values for M1 (P = 0.002) and M2 (P = 0.004). Tongue resting pressure decreases from the anterior aspect to the posterior aspect in the upright position. In the supine position, the pressure is consistent across the midline with pressure enhancement at M1 and M2. As many questions remain about this appliance and appropriate intruding force, further clinical and basic studies are required prior to its clinical implementation.


    Directory of Open Access Journals (Sweden)

    E. Ya. Sadin


    Full Text Available The paper analyzes advantages and disadvantages of composite reinforcement while reinforcing concrete structures. Results of experimental investigations on adhesion strength of fiberglass reinforcement manufactured in the Republic of Belarus with concrete have been given in the paper. The paper contains an analysis pertaining to the influence of concrete contact diameter and length of fiberglass reinforcing bars on strength and deformability of adhesion with concrete. Failure behavior of prototypes and maximum loading that does cause breakage in adhesion of fiberglass reinforcement with the concrete have been controlled in order to study the influence of diameter and length of fiberglass reinforcing bar contact with the concrete on strength and deformability of concrete adhesion for composite reinforcement produced by various manufacturers. Displacement of non-loaded (free and loaded ends of the reinforcing bars with regard to concrete exposed face on both specimen ends has been also controlled. The experiments have shown that destruction of the prototypes occurred due to initiation of one of the following three reasons: reinforcement sliding in reference to concrete, cleaving of a protective concrete layer or breakage of composite reinforcement. Start-up moments for reinforcing bar slip in relation to the concrete have been determined with the help of two methods. The paper provides proposals for calculation assessment of anchorage in the concrete for fiberglass reinforcement manufactured by the following enterprises and companies “Stroykompozit” (Gomel, Republic of Belarus, Research and Production Company (RPC “Biznes-Kontinent” (Brest, Republic of Belarus and Private Eenterprise (PE “Minplast” (Minsk, Republic of Belarus.

  7. A temporal study of urban development for the municipality of Anchorage, Alaska (United States)

    Markon, Carl J.


    A land use/land cover database was produced for a portion of the Municipality of Anchorage, Alaska to document the temporal and spatial extent of urbanization to assist in the analysis of changes in impervious cover and water quality. Data were derived from black and white and color infrared aerial photography, and satellite imagery from the early 1970's to 2000 in roughly ten‐year increments. Aerial photographs and satellite data were manually interpreted to identify and map land use/land cover classes which were then entered into a geographic information system, attributed, and georeferenced to a U.S. Geological Survey topographic map base. The spatial extent of the study was 31,117 hectares. In the early 1970's, approximately 7,356 hectares (24%) of the study area were mapped as urban developed. During the 30‐year analysis period, the largest increase in urban development occurred between the late 1970's and early 1980's when urban area increased to 12,263 hectares (39%). Between 1980 and 1990, and 1990 and 2000, urban area increased to 12,762 hectares (41%), and 13,980 hectares (45%) respectively. Most development occurred in forested or tall shrub areas, although some also occurred in wetlands. Between 1970 and 2000, close to 1,300 hectares of wetlands were lost due to development. Contrary to this, the amount of lake and pond area increased slightly from 261 hectares in 1973 to 334 hectares in 1980, and reduced to 310 hectares by 2000. The increase was primarily due to the filling in of gravel pits with spring melt water.

  8. Preliminary assessment report for Camp Carroll Training Center, Installation 02045, Anchorage, Alaska. Installation Restoration Program

    Energy Technology Data Exchange (ETDEWEB)

    Krokosz, M.; Sefano, J.


    This report presents the results of the preliminary assessment (PA) conducted by Argonne National Laboratory at the Alaska Army National Guard property known as Camp Carroll Training Center, located on the Fort Richardson Army facility near Anchorage, Alaska. Preliminary assessments of federal facilities are being conducted to compile the information necessary for the completion of preremedial activities and to provide a basis for establishing, corrective actions in response to releases of hazardous substances. The principal objective of the PA is to characterize the site accurately and determine the need for further action by examining site activities, types and quantities of hazardous substances used, the nature and amounts of wastes generated or stored at the facility, and potential pathways by which contamination could affect public health and the environment. The primary environmentally significant operations (ESOs) associated with the property are (1) the Alaska Air National Guard storage area behind Building S57112 (Organizational Maintenance Shop [OMS] 6); (2) the state of Alaska maintenance facility and the soil/tar-type spill north of the state of Alaska maintenance facility; (3) the waste storage area adjacent to OMS 6; (4) the contaminated area from leaking underground storage tanks (USTs) and the oil-water separator; and (5) soil staining in the parking area at the Camp Carroll Headquarters Building. Camp Carroll appears to be in excellent condition from an environmental standpoint, and current practices are satisfactory. Argonne recommends that the Alaska Department of Military Affairs consider remediation of soil contamination associated with all storage areas, as well as reviewing the practices of other residents of the facility. Argonne also recommends that the current methods of storing waste material behind Building S57112 (OMS 6) be reviewed for alternatives.

  9. Independent Local Political Parties in the Netherlands

    NARCIS (Netherlands)

    Voerman, G.; Boogers, M.


    In the last 15 years, the Netherlands has witnessed the enormous growth of independent local parties and of their electoral support. In order to assess the success of independent locals in the Netherlands, this paper explores how independent local parties distinguish themselves ideologically, organi

  10. The H19 non-coding RNA is essential for human tumor growth.

    Directory of Open Access Journals (Sweden)

    Imad J Matouk

    Full Text Available BACKGROUND: Mutations and epigenetic aberrant signaling of growth factors pathways contribute to carcinogenesis. Recent studies reveal that non-coding RNAs are controllers of gene expression. H19 is an imprinted gene that demonstrates maternal monoallelic expression without a protein product; although its expression is shut off in most tissues postnatally, it is re-activated during adult tissue regeneration and tumorigenesis. Moreover, H19 is highly expressed in liver metastasis derived from a range of carcinomas. The objective of this study is to explore the role of H19 in carcinogenesis, and to determine its identification as an anti-tumor target. METHODOLOGY/PRINCIPLE FINDINGS: By controlling oxygen pressure during tumor cell growth and H19 expression levels, we investigated the role of H19 expression in vitro and in vivo in hepatocellular (HCC and bladder carcinoma. Hypoxia upregulates the level of H19 RNA. Ablations of tumorigenicity of HCC and bladder carcinomas in vivo are seen by H19 knockdown which also significantly abrogates anchorage-independent growth after hypoxia recovery, while ectopic H19 expression enhances tumorigenic potential of carcinoma cells in vivo. Knocking-down H19 message in hypoxic stress severely diminishes p57(kip2 induction. We identified a number of potential downstream targets of H19 RNA, including angiogenin and FGF18. CONCLUSIONS: H19 RNA harbors pro-tumorigenic properties, thus the H19 gene behaves as an oncogene and may serve as a potential new target for anti-tumor therapy.

  11. Fibroblast growth factor receptors as therapeutic targets in human melanoma: synergism with BRAF inhibition. (United States)

    Metzner, Thomas; Bedeir, Alexandra; Held, Gerlinde; Peter-Vörösmarty, Barbara; Ghassemi, Sara; Heinzle, Christine; Spiegl-Kreinecker, Sabine; Marian, Brigitte; Holzmann, Klaus; Grasl-Kraupp, Bettina; Pirker, Christine; Micksche, Michael; Berger, Walter; Heffeter, Petra; Grusch, Michael


    Cutaneous melanoma is a tumor with rising incidence and a very poor prognosis at the disseminated stage. Melanomas are characterized by frequent mutations in BRAF and also by overexpression of fibroblast growth factor 2 (FGF2), offering opportunities for therapeutic intervention. We investigated inhibition of FGF signaling and its combination with dacarbazine or BRAF inhibitors as an antitumor strategy in melanoma. The majority of melanoma cell lines displayed overexpression of FGF2 but also FGF5 and FGF18 together with different isoforms of FGF receptors (FGFRs) 1-4. Blockade of FGF signals with dominant-negative receptor constructs (dnFGFR1, 3, or 4) or small-molecule inhibitors (SU5402 and PD166866) reduced melanoma cell proliferation, colony formation, as well as anchorage-independent growth, and increased apoptosis. DnFGFR constructs also significantly inhibited tumor growth in vivo. Combination of FGF inhibitors with dacarbazine showed additive or antagonistic effects, whereas synergistic drug interaction was observed when combining FGFR inhibition with the multikinase/BRAF inhibitor sorafenib or the V600E mutant-specific BRAF inhibitor RG7204. In conclusion, FGFR inhibition has antitumor effects against melanoma cells in vitro and in vivo. Combination with BRAF inhibition offers a potential for synergistic antimelanoma effects and represents a promising therapeutic strategy against advanced melanoma.


    Lötsch, D.; Englinger, B.; Pichler, J.; Hainfellner, J.; Marosi, C.; Czech, T.; Knosp, E.; Buchroithner, J.; Spiegl-Kreinecker, S.; Berger, W.


    Glioblastoma growth is driven by receptor tyrosine kinase (RTK)-mediated signals. One of the RTK systems recently coming into focus are the fibroblast growth factor (FGF) high-affinity receptors (FGFR1-FGFR4) due to mutation, overexpression or translocation in several cancer types. FGF/FGFR represents a complex signal network with essential functions in embryonic development, tissue homeostasis and wound healing but also for malignant transformation and growth as well as tumor neoangiogenesis and therapy failure. Several studies have suggested a role of FGFRs in human glioblastoma whereby the information on FGFR4 is sparse. Here we investigated whether FGFR4 as compared to FGFR1 blockade impacts on glioblastoma growth in vitro and in vivo. Both in human glioblastoma cell lines (N = 8) and primary cell cultures from clinical samples (N = 26) we found a widespread expression of several FGFs (e.g. FGF1, FGF2, and FGF5) but also a significant overexpression of FGFR1 and FGFR4 in distinct subgroups as compared to non-malignant brain primo cell cultures. Regarding FGFR1 mRNA, all glioma cell models investigated expressed in addition to the FGFR1-IIIb also the mesenchymal and more oncogenic FGFR1-IIIc splice variant. Application of the FGFR inhibitors (nintedanib, ponatinib) as well as expression of dominant-negative (dn) versions of FGFR1 and FGFR4 significantly reduced in vitro cell growth and clonogenicity in the tested glioma cell models whereby dnFGFR1 tended to be more efficient than dnFGFR4. Accordingly, both dominant-negative FGFRs induced significant apoptosis whereby the effects of dnFGFR1 were again significantly stronger. Surprisingly, the inhibitory effects on anchorage-independent growth in soft agar were opposite with significant mitigation by dnFGFR1 but almost complete blockade by dnFGFR4 in the majority of the glioblastoma models analysed. Additionally, neurosphere formation, indicative for the presence of glioma stem cells, was profoundly reduced by

  13. Inhibitory Effect of CT120B, an Alternative Splice Variant of CT120A,on Lung Cancer Cell Growth

    Institute of Scientific and Technical Information of China (English)

    Dong-Ning PAN; Jin-Jun LI; Lin WEI; Ming YAO; Da-Fang WAN; Jian-Ren GU


    The expression product of ct120a, a novel gene isolated from human chromosome 17p13.3in our laboratory, was predicted to have seven transmembrane domains and could cause malignant transformation of mouse NIH3T3 cells. There existed an mRNA splicing variant of ct120a, namely ct120b,which had a 96-nucleotide deletion and produced an in-frame loss of 32 amino acids from codon 136 to codon 167 of CT120A. The CT120B protein was predicted to have six transmembrane domains. In this study, we observed that the green fluorescent protein-tagged CT120B was localized on plasma membrane and in cytoplasm in SPC-A-1 cells. The expression of CT120B/A in normal lung tissue and in lung cancer cells was also examined. Results showed that the stable CT120B overexpression in SPC-A-1 cells resulted in a reduction of cell growth rate, and inhibited tumorigenecity and anchorage-independent growth in nude mice. The functions of CT120A and CT120B for cell growth appeared antagonistic. We suggested that the delayed G1/S phase transition might contribute to the inhibitory activities of CT120B on cell growth and that the deleted 32 amino acids missing in CT120B might be essential for the oncogenetic activities of CT120A.

  14. Optimization Design of Anchorage Structure for Safety Belt on Rear Floor%后地板安全带固定点结构优化设计

    Institute of Scientific and Technical Information of China (English)

    闻培培; 李宏华; 赵福全


    针对后地板安全带固定点的3种结构形式,对后地板安全带固定点相关法规进行了介绍,并对后排安全带固定点的强度进行了分析.通过分析某车型后地板安全带固定点强度失效原因,对其后地板安全带固定点结构和焊点进行了优化,优化后的结构在模具冲压和车身焊接中均未出现问题,满足了静拉试验相关法规要求.%The three structural types of anchorage point of safety belt on rear floor and the regulations of anchorage point of rear safety belts are introduced in this paper, and the strength of rear seat belt anchorage point is analyzed. By analyzing cause of failure of seat belt anchorage of rear floor of a vehicle model, optimization is made to seat belt anchorage structure and welding point of its rear floor, the optimized structure does not fail either in die stamping nor body welding, and related regulation requirement of static tensile test is thus satisfied.

  15. Fibroblast growth factor receptor-3 (FGFR-3) regulates expression of paneth cell lineage-specific genes in intestinal epithelial cells through both TCF4/beta-catenin-dependent and -independent signaling pathways. (United States)

    Brodrick, Brooks; Vidrich, Alda; Porter, Edith; Bradley, Leigh; Buzan, Jenny M; Cohn, Steven M


    Fibroblast growth factor receptor-3 (FGFR-3) expression in the developing intestine is restricted to the undifferentiated epithelial cells within the lower portion of the crypt. We previously showed that mice lacking functional FGFR-3 have a significant decrease in the number of Paneth cells in the small intestine. Here, we used Caco2 cells to investigate whether FGFR-3 signaling can directly modulate expression of Paneth cell differentiation markers through its effects on TCF4/β-catenin or through other signaling pathways downstream of this receptor. Caco2 cells treated with FGFR-3 ligands or expressing FGFR-3(K650E), a constitutively active mutant, resulted in a significantly increased expression of genes characteristic of mature Paneth cells, including human α-defensins 5 and 6 (HD5 and HD6) and Paneth cell lysozyme, whereas enterocytic differentiation markers were reduced. Activation of FGFR-3 signaling sustained high levels of β-catenin mRNA expression, leading to increased TCF4/β-catenin-regulated transcriptional activity in Caco2 cells. Sustained activity of the TCF4/β-catenin pathway was required for the induction of Paneth cell markers. Activation of the MAPK pathway by FGFR-3 is also required for the induction of Paneth cell markers in addition to and independent of the effect of FGFR-3 on TCF4/β-catenin activity. These studies suggest that coordinate activation of multiple independent signaling pathways downstream of FGFR-3 is involved in regulation of Paneth cell differentiation.

  16. Intrusão dentária utilizando mini-implantes Orthodontic intrusion with mini-implant anchorage

    Directory of Open Access Journals (Sweden)

    Telma Martins de Araújo


    Full Text Available INTRODUÇÃO: dentre os diversos tipos de movimentos dentários induzidos ortodonticamente, o de intrusão é, sem dúvida, um dos mais difíceis de serem conseguidos. A mecânica intrusiva convencional, apesar de viável, é complexa, no que diz respeito ao controle de seus efeitos colaterais. Isso, em grande parte, refere-se à dificuldade em se obter uma ancoragem satisfatória. Neste contexto, os mini-implantes, por oferecerem efetiva ancoragem esquelética, têm se mostrado de extrema valia para os ortodontistas, tornando a intrusão, tanto de dentes anteriores quanto posteriores, um procedimento cada vez mais simples, do ponto de vista mecânico. OBJETIVO: pretende-se, então, neste artigo, descrever e demonstrar, clinicamente, as diversas possibilidades de utilização dos mini-implantes como recurso de ancoragem para o movimento de intrusão.INTRODUCTION: Among all different varieties of orthodontically induced tooth movement, intrusion is, without doubt, one of the most difficult movements to be reached. Conventional intrusive biomechanics, although possible, may lead to undesirable side-effects. These events, in most cases, are related to the difficulty in obtaining an efficient anchorage unit. Then, mini-implants, because of their high success rates of effective skeletal anchorage, are valuable devices to orthodontists, transforming the intrusion movement, both at the anterior and the posterior regions, a more and more uncomplicated biomechanical procedure. AIM: to describe and show, clinically, different ways of using mini-implants as an anchorage system to intrusion movement.

  17. Study on Fatigue Behavior of Anchorage of Cable and Girder of Long Span Cable-Stayed Bridge

    Institute of Scientific and Technical Information of China (English)


    A full scale model test is done and a FEM model is established toinvestigate the fatigue behavior of the Nancha cable-stayed bridge of the Nanjing Second Yangtz River Bridge, a long span steel bridge with a main span of 628 m. The results of test and FEM are analyzed and compared. It is shown that they are in good agreement. It is verified that the fatigue characteristic of the anchorage structure of cable and girder of the bridge satisfies the requirements specified by Chinese, British and American codes.

  18. Abrogation of heat-shock protein (HSP)70 expression induced cell growth inhibition and apoptosis in human androgen-independent prostate cancer cell line PC-3m

    Institute of Scientific and Technical Information of China (English)

    Zhi-GangZhao; Qing-ZhengMa; Chun-XiaoXu


    Aim: To investigate the effect of abrogating heat shock protein (HSP) 70 expression by antisense HSP70 oligonucleotides treatment on human androgen-independent prostate cancer cell line PC-3m growth. Methods: PC3m cells were treated with 0-16μmol/L antisense HSP70 oligomers for 0-100 hr. Cell growth inhibition was analyzed using a trypan blue dye exclusion test. Apoptotic cells were detected and confirmed by flow cytometric analysis and DNA fragmentation analysis. The protein expression of HSP70 and bcl-2 affected by antisense HSP70 oligomers were determined using Western blot. Results: Antisense HSP70 oligomer induced apoptosis and then inhibited proliferation of PC-3m cells in a dose- and time-dependent manner. Ladder-like patterns of DNA fragments were observed in PC-3m cells treated with 10μmol/L antisense HSP70 oligomer for 48 hr or 8μtmol/L for 72 hr on agarose gel electrophoresis. Antisense HSP70 oligomer pretreatment enhanced the subsequent induction of apoptosis by heat shock in PC-3m cells. In addition, undetectable HSP70 expression was observed at a concentration of 10μtmol/L antisense HSP70 oligomer treatment for 48 hr or 8μtmol/L for 72 hr in Western blot, which was paralleled by decreased expression levels of anti-apoptotic protein bcl-2. Conclusion: HSP70 antisense oligomer treatment abro-gates the expression of HSP70, which may disrupt HSP70-bcl-2-interactions and further down-regulate bcl-2 expression,in turn inducing apoptosis and inhibiting cell growth in PC-3m cells. (Asian JAndro12004 Dec;6:319-324)

  19. GRP78 and Cripto Form a Complex at the Cell Surface and Collaborate To Inhibit Transforming Growth Factor β Signaling and Enhance Cell Growth▿ (United States)

    Shani, Gidi; Fischer, Wolfgang H.; Justice, Nicholas J.; Kelber, Jonathan A.; Vale, Wylie; Gray, Peter C.


    Cripto is a multifunctional cell surface protein with important roles in vertebrate embryogenesis and the progression of human tumors. While Cripto has been shown to modulate multiple signaling pathways, its binding partners do not appear to fully explain its molecular actions. Therefore, we conducted a screen aimed at identifying novel Cripto-interacting proteins. This screen led to our identification of glucose-regulated protein 78 (GRP78), an endoplasmic reticulum (ER) chaperone that is also expressed at the surfaces of tumor cells. Here we demonstrate that Cripto and GRP78 interact at the cell surfaces of multiple cell lines and that their interaction is independent of prior association within the ER. Interestingly, short hairpin RNA knockdown of endogenous GRP78 resulted in enhanced transforming growth factor β (TGF-β) signaling, indicating that like Cripto, GRP78 inhibits this pathway. We further show that when coexpressed, GRP78 and Cripto collaborate to antagonize TGF-β responses, including Smad phosphorylation and growth inhibition of prostate cancer cells grown under anchorage-dependent or -independent conditions. Finally, we provide evidence that cells coexpressing GRP78 and Cripto grow much more rapidly in soft agar than do cells expressing either protein individually. Together, our results indicate that these proteins bind at the cell surface to enhance tumor growth via the inhibition of TGF-β signaling. PMID:17991893

  20. Combined maxillary and mandibular midline and mandibular ramus distraction osteogenesis for treatment of a Class II patient with implants as orthodontic anchorage. (United States)

    Takahashi, Ichiro; Kawamura, Hiroshi; Takano-Yamamoto, Teruko


    This case report describes the treatment of a woman with severe mandibular retrusion and maxillomandibular transverse deficiency. Her malocclusion was characterized by a large overjet, a deep overbite, and a V-shaped dental arch, and she had a skeletal Class II profile. Treatement included combined maxillary and mandibular midline expansion, maxillary downward repositioning, and mandibular ramus lengthening with distraction osteogenesis with implants as orthodontic anchorage. During the postdistraction orthodontic treatment period, some skeletal relapse occurred. Implants provided absolute orthodontic anchorage to overcome the unexpected skeletal changes. Combined orthodontic treatment with implants for anchorage and distraction osteogenesis successfully expanded the maxilla and the mandible and corrected the mandibular deficiency. Two-year follow-up records show a morphologically and functionally stable result.

  1. 种植体支抗在正畸临床上的应用%Implant Anchorage in Orthodontic Clinical Application

    Institute of Scientific and Technical Information of China (English)



    目的:探讨种植体支抗在正畸临床治疗。方法对20例种植体支抗的正畸治疗应用方法及临床应用体会。结果20例种植体支抗,微镙钉种植16例,钛板种植体3例,修复种植体1例。种植体均保持了稳定,种植体周围软组织健康,脱落率10%。结论牙齿的缺失造成支抗的不足,某些类型的牙齿移动难以或不能完成。将钛合金牙种植体作为支抗完成正畸治疗,正畸治疗结束后,将种植体行永久性修复。%Objective To investigate the implant anchorage in orthodontic clinical treatment. Methods 20 cases of implant anchorage orthodontic treatment application methods and clinical application experience. Results 20 cases of implant anchorage, micro screws planting 16 cases, 3 cases of titanium implants , implant restoration one case . Implants have maintained a stable implant soft tissue health, loss rate of 10%. Conclusion The lack of teeth caused by lack of anchorage, and certain types of tooth movement difficult or impossible to complete. The titanium dental implants as orthodontic anchorage is completed, after the end of orthodontic treatment, the implant permanently repair the line, traditional dental implant anchorage to be more widely used in orthodontic patients with a combination therapy of implant restoration.

  2. Bst1 is required for Candida albicans infecting host via facilitating cell wall anchorage of Glycosylphosphatidyl inositol anchored proteins (United States)

    Liu, Wei; Zou, Zui; Huang, Xin; Shen, Hui; He, Li Juan; Chen, Si Min; Li, Li Ping; Yan, Lan; Zhang, Shi Qun; Zhang, Jun Dong; Xu, Zheng; Xu, Guo Tong; An, Mao Mao; Jiang, Yuan Ying


    Glycosylphosphatidyl inositol anchored proteins (GPI-APs) on fungal cell wall are essential for invasive infections. While the function of inositol deacylation of GPI-APs in mammalian cells has been previously characterized the impact of inositol deacylation in fungi and implications to host infection remains largely unexplored. Herein we describe our identification of BST1, an inositol deacylase of GPI-Aps in Candida albicans, was critical for GPI-APs cell wall attachment and host infection. BST1-deficient C. albicans (bst1Δ/Δ) was associated with severely impaired cell wall anchorage of GPI-APs and subsequen unmasked β-(1,3)-glucan. Consistent with the aberrant cell wall structures, bst1Δ/Δ strain did not display an invasive ability and could be recognized more efficiently by host immune systems. Moreover, BST1 null mutants or those expressing Bst1 variants did not display inositol deacylation activity and exhibited severely attenuated virulence and reduced organic colonization in a murine systemic candidiasis model. Thus, Bst1 can facilitate cell wall anchorage of GPI-APs in C. albicans by inositol deacylation, and is critical for host invasion and immune escape. PMID:27708385

  3. Combination of antibody that inhibits ligand-independent HER3 dimerization and a p110α inhibitor potently blocks PI3K signaling and growth of HER2+ breast cancers. (United States)

    Garrett, Joan T; Sutton, Cammie R; Kurupi, Richard; Bialucha, Carl Uli; Ettenberg, Seth A; Collins, Scott D; Sheng, Qing; Wallweber, Jerry; Defazio-Eli, Lisa; Arteaga, Carlos L


    We examined the effects of LJM716, an HER3 (ERBB3) neutralizing antibody that inhibits ligand-induced and ligand-independent HER3 dimerization, as a single agent and in combination with BYL719, an ATP competitive p110α-specific inhibitor, against HER2-overexpressing breast and gastric cancers. Treatment with LJM716 reduced HER2-HER3 and HER3-p85 dimers, P-HER3 and P-AKT, both in vitro and in vivo. Treatment with LJM716 alone markedly reduced growth of BT474 xenografts. The combination of LJM716/lapatinib/trastuzumab significantly improved survival of mice with BT474 xenografts compared with lapatinib/trastuzumab (P = 0.0012). LJM716 and BYL719 synergistically inhibited growth in a panel of HER2+ and PIK3CA mutant cell lines. The combination also inhibited P-AKT in HER2-overexpressing breast cancer cells and growth of HER2+ NCI-N87 gastric cancer xenografts more potently than LJM716 or BYL719 alone. Trastuzumab-resistant HER2+/PIK3CA mutant MDA453 xenografts regressed completely after 3 weeks of therapy with LJM716 and BYL719, whereas either single agent inhibited growth only partially. Finally, mice with BT474 xenografts treated with trastuzumab/LJM716, trastuzumab/BYL719, LJM716/BYL719, or trastuzumab/LJM716/BYL719 exhibited similar rates of tumor regression after 3 weeks of treatment. Thirty weeks after treatment discontinuation, 14% of mice were treated with trastuzumab/LJM716/BYL719, whereas >80% in all other treatment groups were sacrificed due to a recurrent large tumor burden (P = 0.0066). These data suggest that dual blockade of the HER2 signaling network with an HER3 antibody that inhibits HER2-HER3 dimers in combination with a p110α-specific inhibitor in the absence of a direct HER2 antagonist is an effective treatment approach against HER2-overexpressing cancers.

  4. Altered Fibroblast Growth Factor Receptor 4 Stability Promotes Prostate Cancer Progression

    Directory of Open Access Journals (Sweden)

    Jianghua Wang


    Full Text Available Fibroblast growth factor receptor 4 (FGFR-4 is expressed at significant levels in almost all human prostate cancers, and expression of its ligands is ubiquitous. A common polymorphism of FGFR-4 in which arginine (Arg388 replaces glycine (Gly388 at amino acid 388 is associated with progression in human prostate cancer. We show that the FGFR-4 Arg388 polymorphism, which is present in most prostate cancer patients, results in increased receptor stability and sustained receptor activation. In patients bearing the FGFR-4 Gly388 variant, expression of Huntingtin-interacting protein 1 (HIP1, which occurs in more than half of human prostate cancers, also results in FGFR-4 stabilization. This is associated with enhanced proliferation and anchorage-independent growth in vitro. Our findings indicate that increased receptor stability and sustained FGFR-4 signaling occur in most human prostate cancers due to either the presence of a common genetic polymorphism or the expression of a protein that stabilizes FGFR-4. Both of these alterations are associated with clinical progression in patients with prostate cancer. Thus, FGFR-4 signaling and receptor turnover are important potential therapeutic targets in prostate cancer.

  5. Suppression of cell growth and invasion by miR-205 in breast cancer

    Institute of Scientific and Technical Information of China (English)

    Hailong Wu; Shoumin Zhu; Yin-Yuan Mo


    MicroRNAs (miRNAs) are endogenous, small, non-coding RNAs, which are capable of silencing gene expression at the post-transcriptional level. In this study, we report that miR-205 is significantly underexpressed in breast tumor compared to the matched normal breast tissue. Similarly, breast cancer cell lines, including MCF-7 and MDA-MB-231, express a lower level miR-205 than the non-malignant MCF-10A cells. Of interest, ectopic expression of miR-205 significantly inhibits cell proliferation and anchorage independent growth, as well as cell invasion. Furthermore, miR-205 was shown to suppress lung metastasis in an animal model. Finally, western blot combined with the luciferase reporter assays demonstrate that ErbB3 and vascular endothelial growth factor A (VEGF-A) are direct targets for miR-205, and this miR-205-mediated suppression is likely through the direct interaction with the putative miR-205 binding site in the 3'-untranslated region (3'-UTR) of ErbB3 and VEGF-A. Together, these results suggest that miR-205 is a tumor suppressor in breast cancer.

  6. Parabens enable suspension growth of MCF-10A immortalized, non-transformed human breast epithelial cells. (United States)

    Khanna, Sugandha; Darbre, Philippa D


    Parabens (alkyl esters of p-hydroxybenzoic acid) are used extensively as preservatives in consumer products, and intact esters have been measured in several human tissues. Concerns of a potential link between parabens and breast cancer have been raised, but mechanistic studies have centred on their oestrogenic activity and little attention has been paid to any carcinogenic properties. In the present study, we report that parabens can induce anchorage-independent growth of MCF-10A immortalized but non-transformed human breast epithelial cells, a property closely related to transformation and a predictor of tumour growth in vivo. In semi-solid methocel suspension culture, MCF-10A cells produced very few colonies and only of a small size but the addition of 5 × 10(-4) M methylparaben, 10(-5) M n-propylparaben or 10(-5) M n-butylparaben resulted in a greater number of colonies per dish (P paraben concentrations in human breast tissue samples from 40 mastectomies (Barr et al., 2012) showed that 22/40 of the patients had at least one of the parabens at the site of the primary tumour at or above these concentrations. To our knowledge, this is the first study to report that parabens can induce a transformed phenotype in human breast epithelial cells in vitro, and further investigation is now justified into a potential link between parabens and breast carcinogenesis. Copyright © 2012 John Wiley & Sons, Ltd.

  7. ABI3 ectopic expression reduces in vitro and in vivo cell growth properties while inducing senescence

    Directory of Open Access Journals (Sweden)

    Riggins Gregory J


    Full Text Available Abstract Background Mounting evidence has indicated that ABI3 (ABI family member 3 function as a tumor suppressor gene, although the molecular mechanism by which ABI3 acts remains largely unknown. Methods The present study investigated ABI3 expression in a large panel of benign and malignant thyroid tumors and explored a correlation between the expression of ABI3 and its potential partner ABI3-binding protein (ABI3BP. We next explored the biological effects of ABI3 ectopic expression in thyroid and colon carcinoma cell lines, in which its expression was reduced or absent. Results We not only observed that ABI3 expression is reduced or lost in most carcinomas but also that there is a positive correlation between ABI3 and ABI3BP expression. Ectopic expression of ABI3 was sufficient to lead to a lower transforming activity, reduced tumor in vitro growth properties, suppressed in vitro anchorage-independent growth and in vivo tumor formation while, cellular senescence increased. These responses were accompanied by the up-regulation of the cell cycle inhibitor p21 WAF1 and reduced ERK phosphorylation and E2F1 expression. Conclusions Our result links ABI3 to the pathogenesis and progression of some cancers and suggests that ABI3 or its pathway might have interest as therapeutic target. These results also suggest that the pathways through which ABI3 works should be further characterized.

  8. Noncoding Effects of Circular RNA CCDC66 Promote Colon Cancer Growth and Metastasis. (United States)

    Hsiao, Kuei-Yang; Lin, Ya-Chi; Gupta, Sachin Kumar; Chang, Ning; Yen, Laising; Sun, H Sunny; Tsai, Shaw-Jenq


    Circular RNA (circRNA) is a class of noncoding RNA whose functions remain mostly unknown. Recent studies indicate circRNA may be involved in disease pathogenesis, but direct evidence is scarce. Here, we characterize the functional role of a novel circRNA, circCCDC66, in colorectal cancer. RNA-Seq data from matched normal and tumor colon tissue samples identified numerous circRNAs specifically elevated in cancer cells, several of which were verified by quantitative RT-PCR. CircCCDC66 expression was elevated in polyps and colon cancer and was associated with poor prognosis. Gain-of-function and loss-of-function studies in colorectal cancer cell lines demonstrated that circCCDC66 controlled multiple pathological processes, including cell proliferation, migration, invasion, and anchorage-independent growth. In-depth characterization revealed that circCCDC66 exerts its function via regulation of a subset of oncogenes, and knockdown of circCCDC66 inhibited tumor growth and cancer invasion in xenograft and orthotopic mouse models, respectively. Taken together, these findings highlight a novel oncogenic function of circRNA in cancer progression and metastasis. Cancer Res; 77(9); 2339-50. ©2017 AACR. ©2017 American Association for Cancer Research.

  9. [Suppression of Aurora-A by RNA interference inhibits laryngeal cancer Hep-2 cell growth]. (United States)

    Zhang, Hao; Chen, Xue-hua; Cai, Chang-ping; Wang, Shi-li; Liu, Bing-ya; Zhou, Liang


    To investigate the effects of knockdown of Aurora-A by RNA interference on laryngeal cancer Hep-2 cell growth in vitro and in vivo. A plasmid containing siRNA against Aurora-A was constructed and transfected into human laryngeal cancer cell line Hep-2. Measurements included the CCK-8 assay for viability and proliferation, Transwell assay for invasion, colony formation assay for cell anchorage-independent growth. Western blot and immunohistochemistry assay for protein expression. Tumorigenicity was observed in vivo. In Hep-2 cells transfected by Aurora-A siRNA (designated as siRNA-3), protein expression of Aurora-A was suppressed by 52%. In CCK-8 assay, absorbance value of siRNA-3 cells (3.268 ± 0.106, (x(-) ± s)) was lower than that of Hep-2 cells (3.722 ± 0.152, F = 17.634, P Hep-2 cells (236.0 ± 26.0, F = 26.462, P Hep-2 cells (104.0 ± 14.0). The average tumor size in siRNA-3 group was (127.77 ± 174.83) mm(3), which was less than Hep-2 cell group (837.26 ± 101.80) mm(3), (F = 28.187, P Hep-2 cells in vitro and in vivo, which may be a promising therapeutic strategy for LSCC.

  10. Epidermal growth factor receptor activation in glioblastoma through novel missense mutations in the extracellular domain.

    Directory of Open Access Journals (Sweden)

    Jeffrey C Lee


    Full Text Available BACKGROUND: Protein tyrosine kinases are important regulators of cellular homeostasis with tightly controlled catalytic activity. Mutations in kinase-encoding genes can relieve the autoinhibitory constraints on kinase activity, can promote malignant transformation, and appear to be a major determinant of response to kinase inhibitor therapy. Missense mutations in the EGFR kinase domain, for example, have recently been identified in patients who showed clinical responses to EGFR kinase inhibitor therapy. METHODS AND FINDINGS: Encouraged by the promising clinical activity of epidermal growth factor receptor (EGFR kinase inhibitors in treating glioblastoma in humans, we have sequenced the complete EGFR coding sequence in glioma tumor samples and cell lines. We identified novel missense mutations in the extracellular domain of EGFR in 13.6% (18/132 of glioblastomas and 12.5% (1/8 of glioblastoma cell lines. These EGFR mutations were associated with increased EGFR gene dosage and conferred anchorage-independent growth and tumorigenicity to NIH-3T3 cells. Cells transformed by expression of these EGFR mutants were sensitive to small-molecule EGFR kinase inhibitors. CONCLUSIONS: Our results suggest extracellular missense mutations as a novel mechanism for oncogenic EGFR activation and may help identify patients who can benefit from EGFR kinase inhibitors for treatment of glioblastoma.

  11. Upregulated Expression of a Unique Gene by Hepatitis B x Antigen Promotes Hepatocellular Growth and Tumorigenesis

    Directory of Open Access Journals (Sweden)

    Zhaorui Lian


    Full Text Available Hepatitis B x antigen (HBxAg is a trans-activating protein that may be involved in hepatocarcinogenesis, although few natural effectors of HBxAg that participate in this process have been identified. To identify additional effectors, whole cell RNA isolated from HBxAg-positive and HBxAg-negative HepG2 cells were compared by polymerase chain reaction select cDNA subtraction, and one clone, upregulated gene, clone 11 (URG11, was chosen for further characterization. Elevated levels of URG11 mRNA and protein were observed in HBxAg-positive compared to HBxAg-negative HepG2 cells. Costaining was observed in infected liver (P<.01. URG11 stimulated cell growth in culture (P<.01, anchorage-independent growth in soft agar (P<.001, and accelerated tumor formation (P<.01, and yielded larger tumors (P<.02 in SCID mice injected subcutaneously with HepG2 cells. These data suggest that URG11 is a natural effector of HBxAg that may promote the development of hepatocellular carcinoma.

  12. Bcl-2 and N-Myc Coexpression Increases IGF-IR and Features of Malignant Growth in Neuroblastoma Cell Lines

    Directory of Open Access Journals (Sweden)

    Rama Jasty


    Full Text Available The bcl-2 and c-myc oncogenes cooperate to transform multiple cell types. In the pediatric malignancy NB2, Bcl2 is highly expressed. In tumors with a poor prognosis, N-Myc, a protein homologous to c-Myc, is overexpressed as a result of gene amplification. The present study was designed to determine whether Bcl-2 cooperates with N-Myc to bestow a tumorigenic phenotype to neuroblastoma (NB cells. NB cell lines that at baseline express neither Bcl-2 nor N-Myc were stably transfected to express these gene products. In this model, we found Bcl-2 rescues N-Myc-expressing cells from apoptosis induced by serum withdrawal. Coexpression of Bcl-2 and N-Myc supports growth in low serum conditions and anchorage-independent growth in soft agar. Similarly, in vivo tumorigenic and angiogenic activity was dependent on coexpression. Our data further suggests that the mechanism underlying these changes involves the receptor for insulin growth factor type I (IGF-IR.

  13. Purification of a high molecular weight form of epidermal growth factor from urine of breast cancer patients. (United States)

    Eckert, K; Granetzny, A; Fischer, J; Grosse, R


    A high molecular weight form of epidermal growth factor (EGF) was detected by means of an EGF radio-receptor assay and an anchorage-independent growth assay in the urine of breast cancer patients. Preliminary data indicate that the activity of this growth factor is associated with lymph node status and tumor size and that the activity becomes reduced after removal of the primary tumor. The EGF-related polypeptide was purified to homogeneity by a combination of Sephadex G-25 and Bio Gel P-30 chromatography followed by binding to, and elution from, EGF receptor rich A431 cells. Final purification was achieved after isoelectric focusing by following the biological activity of eluted polypeptides. A polypeptide of a pI of 3.4 was identified to carry EGF-like activity. This polypeptide migrated as a single band of 43 kDa in SDS-PAGE. Its biological activity was neutralized by a specific anti-hEGF-antibody indicating an immunological relationship with hEGF.

  14. Forced Trefoil Factor Family Peptide 3 (TFF3) Expression Reduces Growth, Viability, and Tumorigenicity of Human Retinoblastoma Cell Lines. (United States)

    Große-Kreul, Jan; Busch, Maike; Winter, Claudia; Pikos, Stefanie; Stephan, Harald; Dünker, Nicole


    Trefoil factor family (TFF) peptides have been shown to effect cell proliferation, apoptosis, migration and invasion of normal cells and various cancer cell lines. In the literature TFF peptides are controversially discussed as tumor suppressors and potential tumor progression factors. In the study presented, we investigated the effect of TFF3 overexpression on growth, viability, migration and tumorigenicity of the human retinoblastoma cell lines Y-79, WERI-Rb1, RBL-13 and RBL-15. As revealed by WST-1 and TUNEL assays as well as DAPI and BrdU cell counts, recombinant human TFF3 significantly lowers retinoblastoma cell viability and increases apoptosis levels. Transient TFF3 overexpression likewise significantly increases RB cell apoptosis. Stable, lentiviral TFF3 overexpression lowers retinoblastoma cell viability, proliferation and growth and significantly increases cell death in retinoblastoma cells. Blockage experiments using a broad-spectrum caspase inhibitor and capase-3 immunocytochemistry revealed the involvement of caspases in general and of caspase-3 in particular in TFF3 induced apoptosis in retinoblastoma cell lines. Soft agarose and in ovo chicken chorioallantoic membrane (CAM) assays revealed that TFF3 overexpression influences anchorage independent growth and significantly decreases the size of tumors forming from retinoblastoma cells. Our study demonstrates that forced TFF3 expression exerts a significant pro-apoptotic, anti-proliferative, and tumor suppressive effect in retinoblastoma cells, setting a starting point for new additive chemotherapeutic approaches in the treatment of retinoblastoma.

  15. Forced Trefoil Factor Family Peptide 3 (TFF3) Expression Reduces Growth, Viability, and Tumorigenicity of Human Retinoblastoma Cell Lines (United States)

    Winter, Claudia; Pikos, Stefanie; Stephan, Harald; Dünker, Nicole


    Trefoil factor family (TFF) peptides have been shown to effect cell proliferation, apoptosis, migration and invasion of normal cells and various cancer cell lines. In the literature TFF peptides are controversially discussed as tumor suppressors and potential tumor progression factors. In the study presented, we investigated the effect of TFF3 overexpression on growth, viability, migration and tumorigenicity of the human retinoblastoma cell lines Y-79, WERI-Rb1, RBL-13 and RBL-15. As revealed by WST-1 and TUNEL assays as well as DAPI and BrdU cell counts, recombinant human TFF3 significantly lowers retinoblastoma cell viability and increases apoptosis levels. Transient TFF3 overexpression likewise significantly increases RB cell apoptosis. Stable, lentiviral TFF3 overexpression lowers retinoblastoma cell viability, proliferation and growth and significantly increases cell death in retinoblastoma cells. Blockage experiments using a broad-spectrum caspase inhibitor and capase-3 immunocytochemistry revealed the involvement of caspases in general and of caspase-3 in particular in TFF3 induced apoptosis in retinoblastoma cell lines. Soft agarose and in ovo chicken chorioallantoic membrane (CAM) assays revealed that TFF3 overexpression influences anchorage independent growth and significantly decreases the size of tumors forming from retinoblastoma cells. Our study demonstrates that forced TFF3 expression exerts a significant pro-apoptotic, anti-proliferative, and tumor suppressive effect in retinoblastoma cells, setting a starting point for new additive chemotherapeutic approaches in the treatment of retinoblastoma. PMID:27626280

  16. Knockdown of hepatoma-derived growth factor-related protein-3 induces apoptosis of H1299 cells via ROS-dependent and p53-independent NF-κB activation

    Energy Technology Data Exchange (ETDEWEB)

    Yun, Hong Shik [Division of Radiation Cancer Biology, Korea Institute of Radiological and Medical Sciences, Seoul 139-706 (Korea, Republic of); Department of Life Science, College of Natural Sciences, Hanyang University, Seoul 133-791 (Korea, Republic of); Baek, Jeong-Hwa [Division of Radiation Cancer Biology, Korea Institute of Radiological and Medical Sciences, Seoul 139-706 (Korea, Republic of); Department of Molecular Cell Biology, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon 440-746 (Korea, Republic of); Yim, Ji-Hye [Division of Radiation Cancer Biology, Korea Institute of Radiological and Medical Sciences, Seoul 139-706 (Korea, Republic of); Lee, Su-Jae [Department of Life Science, College of Natural Sciences, Hanyang University, Seoul 133-791 (Korea, Republic of); Lee, Chang-Woo [Department of Molecular Cell Biology, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon 440-746 (Korea, Republic of); Song, Jie-Young; Um, Hong-Duck; Park, Jong Kuk; Park, In-Chul [Division of Radiation Cancer Biology, Korea Institute of Radiological and Medical Sciences, Seoul 139-706 (Korea, Republic of); Hwang, Sang-Gu, E-mail: [Division of Radiation Cancer Biology, Korea Institute of Radiological and Medical Sciences, Seoul 139-706 (Korea, Republic of)


    Highlights: • HRP-3 is a radiation- and anticancer drug-responsive protein in H1299 cells. • Depletion of HRP-3 induces apoptosis of radio- and chemoresistant H1299 cells. • Depletion of HRP-3 promotes ROS generation via inhibition of the Nrf2/HO-1 pathway. • ROS generation enhances NF-κB activity, which acts as an upstream signal in the c-Myc/Noxa apoptotic pathway. - Abstract: We previously identified hepatoma-derived growth factor-related protein-3 (HRP-3) as a radioresistant biomarker in p53 wild-type A549 cells and found that p53-dependent induction of the PUMA pathway was a critical event in regulating the radioresistant phenotype. Here, we found that HRP-3 knockdown regulates the radioresistance of p53-null H1299 cells through a distinctly different molecular mechanism. HRP-3 depletion was sufficient to cause apoptosis of H1299 cells by generating substantial levels of reactive oxygen species (ROS) through inhibition of the Nrf2/HO-1 antioxidant pathway. Subsequent, ROS-dependent and p53-independent NF-κB activation stimulated expression of c-Myc and Noxa proteins, thereby inducing the apoptotic machinery. Our results thus extend the range of targets for the development of new drugs to treat both p53 wild-type or p53-null radioresistant lung cancer cells.

  17. Remains of the ancient ports and anchorage points at Miyani and Visawada, on the west coast of India: A study based on underwater investigations

    Digital Repository Service at National Institute of Oceanography (India)

    Gaur, A.S.; Sundaresh; Tripati, S.

    as an excellent natural harbour. The important antiquities include varieties of stone anchors, which are very similar to those reported from Dwarka and Bet Dwarka. The identification of ancient anchorage points between water depth of 5 and 15 m is another...

  18. Quantitative and qualitative assessment of anchorage loss during en-masse retraction with indirectly loaded miniscrews in patients with bimaxillary protrusion. (United States)

    Monga, Nitika; Kharbanda, Om Prakash; Samrit, Vilas


    This study provides vital insight in assessing anchorage loss when miniscrews are indirectly loaded. The study sample comprised 18 patients with bimaxillary protrusion (14 girls, 4 boys; mean age, 17.3 ± 4.6 years) selected from a database of 89 patients treated with miniscrews. All subjects who were selected required extraction of all first premolars and maximum anchorage. After initial leveling and aligning, miniscrews were placed between the first molar and the second premolar in all 4 quadrants and loaded by the indirect method at 3 weeks after placement with 200-g nickel-titanium alloy closed-coil springs for en-masse retraction. Mean treatment duration was 29.7 ± 6.8 months. Pretreatment and posttreatment lateral cephalograms were analyzed to measure the amount of anchorage loss, incisor retraction, and the incisors' angular change in reference to the pterygoid vertical reference line and were evaluated by the structural superimposition method. The ratio of incisor retraction to molar protraction was 4.2 in the maxilla and 4.7 in the mandible. The first molars showed mean extrusion of 0.20 mm in the maxilla and 0.57 mm in the mandible; these were statistically insignificant. The mean angular change of the first molars was -2.43° in the maxilla and -0.03° in the mandible. The mean anchorage loss in reference to the pterygoid vertical was 1.3 mm in the maxilla and 1.1 mm in the mandible; these were statistically significant. Structural superimpositions showed mean change in molar position of 0.83 mm in the maxilla and 0.87 mm in the mandible, and 5.77 mm in the maxillary incisor and 5.43 mm in the mandibular incisor. These results were compared with the direct anchorage method reported in the literature. Indirect miniscrew anchorage can be a viable alternative to direct anchorage. Copyright © 2016. Published by Elsevier Inc.

  19. Recombinant differential anchorage probes that tower over the spatial dimension of intracellular signals for high content screening and analysis. (United States)

    Schembri, Laura; Zanese, Marion; Depierre-Plinet, Gaelle; Petit, Muriel; Elkaoukabi-Chaibi, Assia; Tauzin, Loic; Florean, Cristina; Lartigue, Lydia; Medina, Chantal; Rey, Christophe; Belloc, Francis; Reiffers, Josy; Ichas, François; De Giorgi, Francesca


    Recombinant fluorescent probes allow the detection of molecular events inside living cells. Many of them exploit the intracellular space to provide positional signals and, thus, require detection by single cell imaging. We describe here a novel strategy based on probes capable of encoding the spatial dimension of intracellular signals into "all-or-none" fluorescence intensity changes (differential anchorage probes, DAPs). The resulting signals can be acquired in single cells at high throughput by automated flow cytometry, (i) bypassing image acquisition and analysis, (ii) providing a direct quantitative readout, and (iii) allowing the exploration of large experimental series. We illustrate our purpose with DAPs for Bax and the effector caspases 3 and 7, which are keys players in apoptotic cell death, and show applications in basic research, high content multiplexed library screening, compound characterization, and drug profiling.

  20. A Study of the system control model of caisson dewatering of the north anchorage of Taizhou Bridge

    Institute of Scientific and Technical Information of China (English)

    Zhao Yanrong; Zhou Zhifang; Ruan Jing


    A caisson foundation is applied to the north anchorage of Taizhou Yangtze River Highway Bridge of which the initial caisson sinking requires dewatering. Since the caisson foundation is quite close to nearby buildings, a system control model is established with source (sink) distribution and intensity being the object function, minimum requirements of settlement and deformation of surroundings caused by dewatering and dynamic water levels during different working procedures being constraints, and the design parameter of pumping wells being the variable, so as to lower the jeopardizing of surrounding buildings, which provides a new method for active control over settlement during dewatering. Such a method of dewatering based on system control model should be of significance for similar projects involving dewatering.

  1. [Low-cost simple anchorage systems in the removable hybrid prosthesis. Locator Root Attachment and Würzburg post]. (United States)

    Teubner, Eckart; Galindo, Martha L; Arnold, Dario; Marinello, Carlo P


    For a simple and provisional retention of a removable prosthesis, less expensive direct retainers are an option compared to indirect cast gold copings with attachment. The Dalbo-Rotex-retainer and the Ticap-system are clinically established. The Locator Root attachment and the Würzburger Stift were recently introduced. The Locator Root attachment uses a massive profiled cylindrical post as a radicular anchorage. The Würzburger Stift has a small endodontic part which is retained by four spreadable lamellae in a convergent cavity. They further differ in the design of the male and female part. Depending on the clinical situation these characteristics can offer benefits and disadvantages. Both systems are documented and their indication, advantages and restrictions are discussed with clinical relevance.

  2. Anchorage of TiO2-blasted, HA-coated, and machined implants: an experimental study with rabbits

    DEFF Research Database (Denmark)

    Gotfredsen, K; Wennerberg, A; Johansson, C


    The purpose of this study was to evaluate the histometrical and biomechanical anchorage of TiO2-blasted implants and TiO2-blasted implants coated with hydroxyapatite. The control implants were machined. Twenty-six rabbits had a total of 156 implants placed in the proximal part of the tibia. Each...... rabbit had a machined, a TiO2-blasted, and a TiO2-blasted, HA-coated implant placed in each tibia. After a healing period of 3 and 12 weeks, respectively, the implants placed in the right tibia were used for removal torque test, and the implants placed in the left tibia were used for histomorphometrical...... measurements. Preoperatively, implants from the same batches were examined topographically with a TopScan 3D system. The TiO2-blasted implants demonstrated significantly higher removal torque values than the machined implants, and they also had a significantly more irregular surface. Furthermore, significantly...

  3. Cinacalcet lowering of serum fibroblast growth factor-23 concentration may be independent from serum Ca, P, PTH and dose of active vitamin D in peritoneal dialysis patients: a randomized controlled study (United States)


    Background Elevated serum level of fibroblast growth factor-23 (FGF23) is associated with adverse outcomes in dialyzed patients. Objectives The CUPID study compared the efficacy of a cinacalcet-based regimen with conventional care (vitamin D and P binders) for achieving the stringent NKF-K/DOQI targets for peritoneal dialysis (PD) patients. Additionally, we analyzed change in FGF23 levels between two treatments to explore the cinacalcet effect in lowering FGF23. Design Multicenter, open-labeled, randomized controlled study. Setting Seven university-affiliated hospitals in Korea. Participants Overall, 66 peritoneal dialysis patients were enrolled. Intervention Sixty six patients were randomly assigned to treatment with either cinacalcet + oral vitamin D (cinacalcet group, n = 33) or oral vitamin D alone (control group, n = 33) to achieve K/DOQI targets. CUPID included a 4-week screening for vitamin D washout, a 12-week dose-titration, and a 4-week assessment phases. We calculated mean values of iPTH, Ca, P, Ca x P, during assessment phase and final FGF23 to assess the outcome. Main outcome measures Achievement of >30% reduction of iPTH from baseline (primary) and FGF23 reduction (secondary). Results 72.7% (n = 24) of the cinacalcet group and 93.9% (n = 31) of the control group completed the study. Cinacalcet group received 30.2 ± 18.0 mg/day of cinacalcet and 0.13 ± 0.32 μg/d oral vitamin D (P < 0.001 vs. control with 0.27 ± 0.18 μg/d vitamin D). The proportion of patients who reached the primary endpoint was not statistically different (48.5% vs. 51.5%, cinacalcet vs. control, P = 1.000). After treatment, cinacalcet group experienced a significant reduction in FGF23 levels (median value from 3,960 to 2,325 RU/ml, P = 0.002), while an insignificant change was shown for control group (from 2,085 to 2,415 RU/ml). The percent change of FGF23 after treatment was also significantly different between the two groups (− 42.54% vs. 15.83%, P = 0.008). After adjustment

  4. Sulforaphane inhibits platelet-derived growth factor-induced vascular smooth muscle cell proliferation by targeting mTOR/p70S6kinase signaling independent of Nrf2 activation. (United States)

    Shawky, Noha M; Segar, Lakshman


    Activation of nuclear factor erythroid 2-related factor 2 (Nrf2, a transcription factor) and/or inhibition of mammalian target of rapamycin (mTOR) are implicated in the suppression of vascular smooth muscle cell (VSMC) proliferation. The present study has examined the likely regulatory effects of sulforaphane (SFN, an antioxidant) on Nrf2 activation and platelet-derived growth factor (PDGF)-induced mTOR signaling in VSMCs. Using human aortic VSMCs, nuclear extraction and siRNA-mediated downregulation studies were performed to determine the role of Nrf2 on SFN regulation of PDGF-induced proliferative signaling. Immunoprecipitation and/or immunoblot studies were carried out to determine how SFN regulates PDGF-induced mTOR/p70S6K/S6 versus ERK and Akt signaling. Immunohistochemical analysis was performed to determine SFN regulation of S6 phosphorylation in the injured mouse femoral artery. SFN (5μM) inhibits PDGF-induced activation of mTOR without affecting mTOR association with raptor in VSMCs. While SFN inhibits PDGF-induced phosphorylation of p70S6K and 4E-BP1 (downstream targets of mTOR), it does not affect ERK or Akt phosphorylation. In addition, SFN diminishes exaggerated phosphorylation of S6 ribosomal protein (a downstream target of p70S6K) in VSMCs in vitro and in the neointimal layer of injured artery in vivo. Although SFN promotes Nrf2 accumulation to upregulate cytoprotective genes (e.g., heme oxygenase-1 and thioredoxin-1), downregulation of endogenous Nrf2 by target-specific siRNA reveals an Nrf2-independent effect for SFN-mediated inhibition of mTOR/p70S6K/S6 signaling and suppression of VSMC proliferation. Strategies that utilize local delivery of SFN at the lesion site may limit restenosis after angioplasty by targeting mTOR/p70S6K/S6 axis in VSMCs independent of Nrf2 activation. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Analysis of Vehicle Seat Belt Anchorage Strength%汽车安全带固定点强度分析

    Institute of Scientific and Technical Information of China (English)

    邓国红; 杨浩; 杨鄂川; 张勇


    To analyze the vehicle seat belt anchorage strength, the finite element model of body-in- white, seats, seat belts and the body module (hip block, shoulder block cessing software Hypermesh, the explicit solution method in LS-DYNA ) is is established by pre-pro- used, the specified load condition is set according to the national standard, an accurate prediction is made on whether the structure can meet the standard, a method which uses the FEM to analyze the seat belt anchorage strength is found. This method can be extended to other quasi-static strength analysis problems, and analyze the model which is larger and more difficuh to calculate using the implicit integration, which has a strong practicality in product development.%为了进行汽车安全带固定点强度分析,运用有限元分析软件Hypermesh建立白车身、座椅、安全带、人体模块(臀块和肩块)有限元模型。采用LS-DYNA的显式求解模块,按照国家标准设置规定的载荷,分析结构通过标准的可能性。验证了运用有限元显式积分分析汽车安全带固定点强度的方法。该方法可推广到其他准静态强度分析中,用于分析那些比较大的、隐式积分计算比较困难的模型。

  6. Effect of molar intrusion with temporary anchorage devices in patients with anterior open bite: a systematic review

    Directory of Open Access Journals (Sweden)

    Ahmad Saleem Alsafadi


    Full Text Available Abstract Objective The objective of the study is to assess the effect of molar intrusion with temporary anchorage devices on the vertical facial morphology and mandibular rotation during open bite treatment in the permanent dentition. Methods We performed a systematic review of the published data in seven electronic databases up to September 2015. We considered studies for inclusion if they were examining the effects of posterior teeth intrusion on the vertical facial morphology with open bite malocclusion in the permanent dentition. Study selection, risk of bias assessment, and data-extraction were performed in duplicate. Meta-analysis was not possible due to dissimilarity and heterogeneity among the included studies. Results Out of the 42 articles that met the initial eligibility criteria, 12 studies were finally selected. Low level of scientific evidence was identified after risk of bias assessment of the included studies with no relevant randomized controlled trial performed. Out of the 12 selected studies, five studies used miniplates and seven studies used miniscrews. Mandibular counterclockwise rotation was found to be between 2.3° and 3.9° in six studies (as sassed by mandibular plane angle, between MeGo or GoGn and SN or FH plane while it was less than 2° in the remaining studies. Conclusions Current weak evidence suggests that molar intrusion with temporary anchorage devices may cause mandibular counterclockwise autorotation. Future well-conducted and clearly reported multicenter randomized controlled trials that include a non-treatment control group are needed to make robust recommendations regarding the amount of mandibular rotation during open bite treatments.

  7. Characterization of the aspects of osteoprogenitor cell interactions with physical tetracalcium phosphate anchorage on titanium implant surfaces

    Energy Technology Data Exchange (ETDEWEB)

    Ko, Chia-Ling [Advanced Medical Devices and Composites Laboratory, Department of Fiber and Composite Materials, Feng Chia University, Taichung 40724, Taiwan (China); Dental Medical Devices and Materials Research Center, College of Dental Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan (China); Chang, Ya-Yuan; Liou, Cian-Hua [Alliance Global Technology Co., Ltd., Kaohsiung Medical Device Special Zone in Southern Taiwan Science Park, Kaohsiung 82151, Taiwan (China); Chen, Wen-Cheng, E-mail: [Advanced Medical Devices and Composites Laboratory, Department of Fiber and Composite Materials, Feng Chia University, Taichung 40724, Taiwan (China)


    Well-designed implants are used not only to modify the geometry of the implant but also to change the chemical properties of its surfaces. The present study aims to assess the biofunctional effects of tetracalcium phosphate (TTCP) particles as a physical anchor on the implant surface derived through sandblasting. The characteristics of the surface, cell viability, and alkaline phosphatase (ALP) activity toward osteoprogenitor cells (D1) were obtained. D1 cells were cultured on a plain surface that underwent sandblasting and acid etching (SLA) (control SLA group) and on different SLA surfaces with different anchoring TTCP rates (new test groups, M and H). The mean anchoring rates were 57% (M) and 74% (H), and the anchored thickness was estimated to range from 12.6 μm to 18.3 μm. Compared with the control SLA surface on Ti substrate, the new test groups with different TTCP anchoring rates (M and H) failed to improve cell proliferation significantly but had a well-differentiated D1 cell phenotype that enhanced ALP expression in the early stage of cell cultures, specifically, at day 7. Results suggest that the SLA surface with anchored TTCP can accelerate progenitor bone cell mineralization. This study shows the potential clinical application of the constructed geometry in TTCP anchorage on Ti for dental implant surface modification. - Highlights: • TTCP (tetracalcium phosphate) as a physical anchorage on implant is characterized. • Theoretical values of anchored thickness and capping areas were estimated. • TTCP anchored by sandblasting can accelerate progenitor bone cell mineralization. • TTCP anchored on SLA (sandblasting and acid etching) surface is a promising method.

  8. Expression and functional role of orphan receptor GPR158 in prostate cancer growth and progression.

    Directory of Open Access Journals (Sweden)

    Nitin Patel

    Full Text Available Prostate cancer (PCa is the second-leading cause of cancer-related mortality, after lung cancer, in men from developed countries. In its early stages, primary tumor growth is dependent on androgens, thus generally can be controlled by androgen deprivation therapy (ADT. Eventually however, the disease progresses to castration-resistant prostate cancer (CRPC, a lethal form in need of more effective treatments. G-protein coupled receptors (GPCRs comprise a large clan of cell surface proteins that have been implicated as therapeutic targets in PCa growth and progression. The findings reported here provide intriguing evidence of a role for the newly characterized glutamate family member GPR158 in PCa growth and progression. We found that GPR158 promotes PCa cell proliferation independent of androgen receptor (AR functionality and that this requires its localization in the nucleus of the cell. This suggests that GPR158 acts by mechanisms different from other GPCRs. GPR158 expression is stimulated by androgens and GPR158 stimulates AR expression, implying a potential to sensitize tumors to low androgen conditions during ADT via a positive feedback loop. Further, we found GPR158 expression correlates with a neuroendocrine (NE differentiation phenotype and promotes anchorage-independent colony formation implying a role for GPR158 in therapeutic progression and tumor formation. GPR158 expression was increased at the invading front of prostate tumors that formed in the genetically defined conditional Pten knockout mouse model, and co-localized with elevated AR expression in the cell nucleus. Kaplan-Meier analysis on a dataset from the Memorial Sloan Kettering cancer genome portal showed that increased GPR158 expression in tumors is associated with lower disease-free survival. Our findings strongly suggest that pharmaceuticals targeting GPR158 activities could represent a novel and innovative approach to the prevention and management of CRPC.

  9. Are Independent Fiscal Institutions Really Independent?

    Directory of Open Access Journals (Sweden)

    Slawomir Franek


    Full Text Available In the last decade the number of independent fiscal institutions (known also as fiscal councils has tripled. They play an important oversight role over fiscal policy-making in democratic societies, especially as they seek to restore public finance stability in the wake of the recent financial crisis. Although common functions of such institutions include a role in analysis of fiscal policy, forecasting, monitoring compliance with fiscal rules or costing of spending proposals, their roles, resources and structures vary considerably across countries. The aim of the article is to determine the degree of independence of such institutions based on the analysis of the independence index of independent fiscal institutions. The analysis of this index values may be useful to determine the relations between the degree of independence of fiscal councils and fiscal performance of particular countries. The data used to calculate the index values will be derived from European Commission and IMF, which collect sets of information about characteristics of activity of fiscal councils.

  10. Preadult Learning of Political Independence: Media and Family Communication Effects. (United States)

    Dennis, Jack


    Discusses the question of the influence of mass media and interpersonal communication on the growth of partisan independence among American preadults and concludes that preadults become increasingly independent as they get older. (DF)

  11. mad—overexpression down regulates the malignant growth and p53 mediated apoptosis in human hepatocellular carcinoma BEL—7404 cells

    Institute of Scientific and Technical Information of China (English)



    Mad protein has been shown as an antagonist of cMyc protein in some cell lines.The effect of Mad protein to the malignant phenotype of human hepatoma BEL-7404 cell line was investigated experimentally.An eukarryotic vector pCDNA Ⅲ containing full ORF fragment of mad cDNA was transfected into targeted cells.Under G418 selection,stable Mad-overexpressed cells were cloned.Studies on the effect of Mad over-expression in cell proliferation and cell cycle revealed that cell morphology of the Mad-overexpressed BEL-7404-M1 cells was significantly different from the parent and control vector transfected cells.DNA synthesis,cell proliferation and anchorage-independent growth in soft-agar of the madtransfected cells were partially inhibited in comparison to control cells.Flos cytometry analysis indicated that mad over-expression might block more transfectant cells at G0/G1 phase,resulting in the retardation of cell proliferation.RT-PCR detected a marked inhibition of the expression of cdc25A,an important regulator gene of G0/G1 to S phase in cell cycle.It was also found that Mad protein overexpression could greatly suppress p53-mediated apoptosis in BEL-74040M1 cells in the absence of serume.Thus,Mad proteins may function as a negative regulator antagonizing c-Myc activity in the control of cell growth and apoptosis in human hepatocellular carcinoma BEL-7404 cells.

  12. Central Bank independence

    Directory of Open Access Journals (Sweden)

    Vasile DEDU


    Full Text Available In this paper we present the key aspects regarding central bank’s independence. Most economists consider that the factor which positively influences the efficiency of monetary policy measures is the high independence of the central bank. We determined that the National Bank of Romania (NBR has a high degree of independence. NBR has both goal and instrument independence. We also consider that the hike of NBR’s independence played an important role in the significant disinflation process, as headline inflation dropped inside the targeted band of 3% ± 1 percentage point recently.

  13. Mechanical behavior experiment of wedge-bond anchorage for CFRP-tendons%CFRP筋复合型锚具的受力性能试验

    Institute of Scientific and Technical Information of China (English)

    王军; 李明君; 蔡东升; 刘德鑫


    In order to investigate the influence of main design parameters on anchorage performance and internal stress distribution of wedge-bond anchorage for CFRP tendons, five groups of parameter tests on wedge-bond anchorage were designed. The ultimate load, slip deformation of anchor ring and stress of metal sleeve stations were determined. The influence of design parameters on anchorage performance, the tress distribution and variation of metal sleeve were contrastively investigated through static loading testing. The results show that the anchorage performance with metal sleeve thickness of 2 mm, a wedge length of 65 mm, bond length of 500 mm is optimal. The anchor between wedge and metal sleeve is good without relative displacement. The tress distribution and variation of metal sleeve can reflect the internal stress distribution of anchorage, and the perk of stress curve indicates bonding failure between colloid and CFRP tendon near the observation point.%为研究CFRP筋复合型锚具的主要设计参数对锚固性能的影响及锚具内部受力情况,设计了5个复合型锚具的参数静载试验,测量了锚具的极限荷载、锚环-CFRP筋间滑移变形和金属筒测点应变,通过静载试验对比分析了各设计参数对锚固效果的影响,以及金属筒表面应力的分布情况与变化规律.研究结果表明:当金属筒壁厚为2 mm,夹片夹持长度为65 mm,粘结长度为500 mm时,锚具的锚固性能较好;夹片-金属筒间锚固良好,无滑移;金属筒应力分布与变化可反映锚具内部受力情况,测点应力曲线峰值预示该位置附近的胶体与CFRP筋间的粘结破坏.

  14. Control of tissue growth and cell transformation by the Salvador/Warts/Hippo pathway. (United States)

    Zhang, Xiaomeng; Grusche, Felix A; Harvey, Kieran F


    The Salvador-Warts-Hippo (SWH) pathway is an important regulator of tissue growth that is frequently subverted in human cancer. The key oncoprotein of the SWH pathway is the transcriptional co-activator, Yes-associated protein (YAP). YAP promotes tissue growth and transformation of cultured cells by interacting with transcriptional regulatory proteins via its WW domains, or, in the case of the TEAD1-4 transcription factors, an N-terminal binding domain. YAP possesses a putative transactivation domain in its C-terminus that is necessary to stimulate transcription factors in vitro, but its requirement for YAP function has not been investigated in detail. Interestingly, whilst the WW domains and TEAD-binding domain are highly conserved in the Drosophila melanogaster YAP orthologue, Yorkie, the majority of the C-terminal region of YAP is not present in Yorkie. To investigate this apparent conundrum, we assessed the functional roles of the YAP and Yorkie C-termini. We found that these regions were not required for Yorkie's ability to drive tissue growth in vivo, or YAP's ability to promote anchorage-independent growth or resistance to contact inhibition. However, the YAP transactivation domain was required for YAP's ability to induce cell migration and invasion. Moreover, a role for the YAP transactivation domain in cell transformation was uncovered when the YAP WW domains were mutated together with the transactivation domain. This shows that YAP can promote cell transformation in a flexible manner, presumably by contacting transcriptional regulatory proteins either via its WW domains or its transactivation domain.

  15. Control of tissue growth and cell transformation by the Salvador/Warts/Hippo pathway.

    Directory of Open Access Journals (Sweden)

    Xiaomeng Zhang

    Full Text Available The Salvador-Warts-Hippo (SWH pathway is an important regulator of tissue growth that is frequently subverted in human cancer. The key oncoprotein of the SWH pathway is the transcriptional co-activator, Yes-associated protein (YAP. YAP promotes tissue growth and transformation of cultured cells by interacting with transcriptional regulatory proteins via its WW domains, or, in the case of the TEAD1-4 transcription factors, an N-terminal binding domain. YAP possesses a putative transactivation domain in its C-terminus that is necessary to stimulate transcription factors in vitro, but its requirement for YAP function has not been investigated in detail. Interestingly, whilst the WW domains and TEAD-binding domain are highly conserved in the Drosophila melanogaster YAP orthologue, Yorkie, the majority of the C-terminal region of YAP is not present in Yorkie. To investigate this apparent conundrum, we assessed the functional roles of the YAP and Yorkie C-termini. We found that these regions were not required for Yorkie's ability to drive tissue growth in vivo, or YAP's ability to promote anchorage-independent growth or resistance to contact inhibition. However, the YAP transactivation domain was required for YAP's ability to induce cell migration and invasion. Moreover, a role for the YAP transactivation domain in cell transformation was uncovered when the YAP WW domains were mutated together with the transactivation domain. This shows that YAP can promote cell transformation in a flexible manner, presumably by contacting transcriptional regulatory proteins either via its WW domains or its transactivation domain.

  16. Independent repression of bile acid synthesis and activation of c-Jun N-terminal kinase (JNK) by activated hepatocyte fibroblast growth factor receptor 4 (FGFR4) and bile acids. (United States)

    Yu, Chundong; Wang, Fen; Jin, Chengliu; Huang, Xinqiang; McKeehan, Wallace L


    The fibroblast growth factor (FGF) receptor complex is a regulator of adult organ homeostasis in addition to its central role in embryonic development and wound healing. FGF receptor 4 (FGFR4) is the sole FGFR receptor kinase that is significantly expressed in mature hepatocytes. Previously, we showed that mice lacking mouse FGFR4 (mR4(-/-)) exhibited elevated fecal bile acids, bile acid pool size, and expression of liver cholesterol 7alpha-hydroxylase (CYP7A1), the rate-limiting enzyme for canonical neutral bile acid synthesis. To prove that hepatocyte FGFR4 was a negative regulator of cholesterol metabolism and bile acid synthesis independent of background, we generated transgenic mice overexpressing a constitutively active human FGFR4 (CahR4) in hepatocytes and crossed them with the FGFR4-deficient mice to generate CahR4/mR4(-/-) mice. In mice expressing active FGFR4 in liver, fecal bile acid excretion was 64%, bile acid pool size was 47%, and Cyp7a1 expression was 10-30% of wild-type mice. The repressed level of Cyp7a1 expression was resistant to induction by a high cholesterol diet relative to wild-type mice. Expression of CahR4 in mR4(-/-) mouse livers depressed bile acid synthesis below wild-type levels from the elevated levels observed in mR4(-/-). Levels of phosphorylated c-Jun N-terminal kinase (JNK), which is part of a pathway implicated in bile acid-mediated repression of synthesis, was 30% of wild-type levels in mR4(-/-) livers, whereas CahR4 livers exhibited an average 2-fold increase. However, cholate still strongly induced phospho-JNK in mR4(-/-) livers. These results confirm that hepatocyte FGFR4 regulates bile acid synthesis by repression of Cyp7a1 expression. Hepatocyte FGFR4 may contribute to the repression of bile acid synthesis through JNK signaling but is not required for activation of JNK signaling by bile acids.

  17. Intracellular transactivation of epidermal growth factor receptor by α1A-adrenoceptor is mediated by phosphatidylinositol 3-kinase independently of activation of extracellular signal regulated kinases 1/2 and serine-threonine kinases in Chinese hamster ovary cells. (United States)

    Ulu, Nadir; Henning, Robert H; Guner, Sahika; Zoto, Teuta; Duman-Dalkilic, Basak; Duin, Marry; Gurdal, Hakan


    Transactivation of epidermal growth factor receptor (EGFR) by α1-adrenoceptor (α1-AR) is implicated in contraction and hypertrophy of vascular smooth muscle (VSM). We examine whether all α1-AR subtypes transactivate EGFR and explore the mechanism of transactivation. Chinese hamster ovary (CHO) cells stably expressing one subtype of α1-AR were transiently transfected with EGFR. The transactivation mechanism was examined both by coexpression of a chimeric erythropoietin (EPO)-EGFR with an extracellular EPO and intracellular EGFR domain, and by pharmacologic inhibition of external and internal signaling routes. All three α1-AR subtypes transactivated EGFR, which was dependent on the increase in intracellular calcium. The EGFR kinase inhibitor AG1478 [4-(3'-chloroanilino)-6,7-dimethoxyquinazoline] abrogated α1A-AR and α1D-AR induced phosphorylation of EGFR, but both the inhibition of matrix metalloproteinases by GM6001 [(R)-N4-hydroxy-N(1)-[(S)-2-(1H-indol-3-yl)-1-methylcarbamoyl-ethyl]-2-isobutyl-succinamide] or blockade of EGFR by cetuximab did not. Stimulation of α1A-AR and α1D-AR also induced phosphorylation of EPO-EGFR chimeric receptors. Moreover, α1A-AR stimulation enhanced phosphorylation of extracellular signal regulated kinase (ERK) 1/2 and serine-threonine kinases (Akt), which were both unaffected by AG1478, indicating that ERK1/2 and Akt phosphorylation is independent of EGFR transactivation. Accordingly, inhibitors of ERK1/2 or Akt did not influence the α1A-AR-mediated EGFR transactivation. Inhibition of calcium/calmodulin-dependent kinase II (CaMKII), phosphatidylinositol 3-kinase (PI3K), and Src, however, did block EGFR transactivation by α1A-AR and α1D-AR. These findings demonstrate that all α1-AR subtypes transactivate EGFR, which is dependent on an intracellular signaling route involving an increase in calcium and activation of CaMKII, PI3K, and Src, but not the of ERK1/2 and Akt pathways.

  18. Independent candidates in Mexico


    Campos, Gonzalo Santiago


    In this paper we discuss the issue of independent candidates in Mexico, because through the so-called political reform of 2012 was incorporated in the Political Constitution of the Mexican United States the right of citizens to be registered as independent candidates. Also, in September 2013 was carried out a reform of Article 116 of the Political Constitution of the Mexican United States in order to allow independent candidates in each state of the Republic. However, prior to the constitutio...

  19. Central bank Financial Independence


    J.Ramon Martinez-Resano


    Central bank independence is a multifaceted institutional design. The financial component has been seldom analysed. This paper intends to set a comprehensive conceptual background for central bank financial independence. Quite often central banks are modelled as robot like maximizers of some goal. This perspective neglects the fact that central bank functions are inevitably deployed on its balance sheet and have effects on its income statement. A financially independent central bank exhibits ...

  20. A chrysin derivative suppresses skin cancer growth by inhibiting cyclin-dependent kinases. (United States)

    Liu, Haidan; Liu, Kangdong; Huang, Zunnan; Park, Chan-Mi; Thimmegowda, N R; Jang, Jae-Hyuk; Ryoo, In-Ja; He, Long; Kim, Sun-Ok; Oi, Naomi; Lee, Ki Won; Soung, Nak-Kyun; Bode, Ann M; Yang, Yifeng; Zhou, Xinmin; Erikson, Raymond L; Ahn, Jong-Seog; Hwang, Joonsung; Kim, Kyoon Eon; Dong, Zigang; Kim, Bo-Yeon


    Chrysin (5,7-dihydroxyflavone), a natural flavonoid widely distributed in plants, reportedly has chemopreventive properties against various cancers. However, the anticancer activity of chrysin observed in in vivo studies has been disappointing. Here, we report that a chrysin derivative, referred to as compound 69407, more strongly inhibited EGF-induced neoplastic transformation of JB6 P(+) cells compared with chrysin. It attenuated cell cycle progression of EGF-stimulated cells at the G1 phase and inhibited the G1/S transition. It caused loss of retinoblastoma phosphorylation at both Ser-795 and Ser-807/811, the preferred sites phosphorylated by Cdk4/6 and Cdk2, respectively. It also suppressed anchorage-dependent and -independent growth of A431 human epidermoid carcinoma cells. Compound 69407 reduced tumor growth in the A431 mouse xenograft model and retinoblastoma phosphorylation at Ser-795 and Ser-807/811. Immunoprecipitation kinase assay results showed that compound 69407 attenuated endogenous Cdk4 and Cdk2 kinase activities in EGF-stimulated JB6 P(+) cells. Pulldown and in vitro kinase assay results indicated that compound 69407 directly binds with Cdk2 and Cdk4 in an ATP-independent manner and inhibited their kinase activities. A binding model between compound 69407 and a crystal structure of Cdk2 predicted that compound 69407 was located inside the Cdk2 allosteric binding site. The binding was further verified by a point mutation binding assay. Overall results indicated that compound 69407 is an ATP-noncompetitive cyclin-dependent kinase inhibitor with anti-tumor effects, which acts by binding inside the Cdk2 allosteric pocket. This study provides new insights for creating a general pharmacophore model to design and develop novel ATP-noncompetitive agents with chemopreventive or chemotherapeutic potency.

  1. Gravity Independent Compressor Project (United States)

    National Aeronautics and Space Administration — We propose to develop and demonstrate a small, gravity independent, vapor compression refrigeration system using a linear motor compressor which effectively...

  2. A Study on the Relationship between Independent Director Proportion in Family Holding Enterprises and Enterprise Growth---Mediating Effect Test of Innovation Behavior%家族控股公司独立董事比例与企业成长关系研究--创新行为的中介效应

    Institute of Scientific and Technical Information of China (English)

    徐向艺; 尹映集[韩


    In this paper,an empirical research is made on the relationship between independent director proportion, innovation behaviors and business growth in family enterprises based on the data of 310 listed family holding enterprises from 2007 to 2012.It can be concluded that:first,the independent director proportion is conducive to the promotion of in-novation behavior of family holding enterprises;second,the independent director proportion plays a positive role in promo-ting the growth of family holding enterprises;thirdly,innovation behavior is conducive to promoting the growth of family holding enterprises;last,the innovation behavior of family holding enterprises plays a intermediary role between independ-ent director proportion and growth of family enterprise.%本文基于中国310家家族控股的上市公司2007~2012年的经验数据,对其独立董事比例、创新行为和企业成长性之间的关系进行实证研究,得出如下结论:第一,独立董事比例的升高有利于促进家族控股公司的创新行为;第二,独立董事比例的升高对家族控股公司的成长性有正向推动作用;第三,创新行为有利于推动家族控股公司成长;第四,家族控股公司的创新行为在独立董事比例与企业成长之间存在部分中介作用。

  3. Evaluation of the effects of skeletal anchoraged Forsus FRD using miniplates inserted on mandibular symphysis: A new approach for the treatment of Class II malocclusion. (United States)

    Unal, Tuba; Celikoglu, Mevlut; Candirli, Celal


    To evaluate the skeletal, dentoalveolar, and soft tissue effects of the Forsus Fatigue Resistant Device (FRD) appliance with miniplate anchorage for the treatment of skeletal Class II malocclusion. The prospective clinical study group included 17 patients (11 girls and 6 boys; mean age 12.96 ± 1.23 years) with Class II malocclusion due to mandibular retrusion and treated with skeletal anchoraged Forsus FRD. After 0.019 × 0.025-inch stainless steel archwire was inserted and cinched back in the maxillary arch, two miniplates were placed bilaterally on the mandibular symphysis. Then, the Forsus FRD EZ2 appliance was adjusted to the miniplates without leveling the mandibular arch. The changes in the leveling and skeletal anchoraged Forsus FRD phases were evaluated by means of the Paired and Student's t-tests using the cephalometric lateral films. The success rate of the miniplates was found to be 91.5% (38 of 42 miniplates). The mandible significantly moved forward (P overjet correction (-5.11 mm) was found to be mainly by skeletal changes (A-VRL, -1.16 mm and Pog-VRL, 2.62 mm; approximately 74%); the remaining changes were due to the dentoalveolar contributions. The maxillary and mandibular incisors were significantly retruded (P < .001). This new approach was an effective method for treating skeletal Class II malocclusion due to the mandibular retrusion via a combination of skeletal and dentoalveolar changes.

  4. Changes in strain patterns after implantation of a short stem with metaphyseal anchorage compared to a standard stem: an experimental study in synthetic bone

    Directory of Open Access Journals (Sweden)

    Jens Gronewold


    Full Text Available Short stem hip arthroplasties with predominantly metaphyseal fixation, such as the METHA® stem (Aesculap, Tuttlingen, Germany, are recommended because they are presumed to allow a more physiologic load transfer and thus a reduction of stress-shielding. However, the hypothesized metaphyseal anchorage associated with the aforementioned benefits still needs to be verified. Therefore, the METHA short stem and the Bicontact® standard stem (Aesculap, Tuttlingen, Germany were tested biomechanically in synthetic femora while strain gauges monitored their corresponding strain patterns. For the METHA stem, the strains in all tested locations including the region of the calcar (87% of the non-implanted femur were similar to conditions of synthetic bone without implanted stem. The Bicontact stem showed approximately the level of strain of the non-implanted femur on the lateral and medial aspect in the proximal diaphysis of the femur. On the anterior and posterior aspect of the proximal metaphysis the strains reached averages of 78% and 87% of the non-implanted femur, respectively. This study revealed primary metaphyseal anchorage of the METHA short stem, as opposed to a metaphyseal-diaphyseal anchorage of the Bicontact stem.

  5. Accounting for Independent Schools. (United States)

    Sonenstein, Burton

    The diversity of independent schools in size, function, and mode of operation has resulted in a considerable variety of accounting principles and practices. This lack of uniformity has tended to make understanding, evaluation, and comparison of independent schools' financial statements a difficult and sometimes impossible task. This manual has…

  6. Independence of Internal Auditors. (United States)

    Montondon, Lucille; Meixner, Wilda F.


    A survey of 288 college and university auditors investigated patterns in their appointment, reporting, and supervisory practices as indicators of independence and objectivity. Results indicate a weakness in the positioning of internal auditing within institutions, possibly compromising auditor independence. Because the auditing function is…

  7. Fostering Musical Independence (United States)

    Shieh, Eric; Allsup, Randall Everett


    Musical independence has always been an essential aim of musical instruction. But this objective can refer to everything from high levels of musical expertise to more student choice in the classroom. While most conceptualizations of musical independence emphasize the demonstration of knowledge and skills within particular music traditions, this…

  8. A screen for deficiencies in GPI-anchorage of wall glycoproteins in yeast. (United States)

    Gonzalez, Marlyn; Goddard, Noel; Hicks, Charles; Ovalle, Rafael; Rauceo, Jason M; Jue, Chong K; Lipke, Peter N


    Many of the genes and enzymes critical for assembly and biogenesis of yeast cell walls remain unidentified or poorly characterized. Therefore, we designed a high throughput genomic screen for defects in anchoring of GPI-cell wall proteins (GPI-CWPs), based on quantification of a secreted GFP-Sag1p fusion protein. Saccharomyces cerevisiae diploid deletion strains were transformed with a plasmid expressing the fusion protein under a GPD promoter, then GFP fluorescence was determined in culture supernatants after mid-exponential growth. Variability in the amount of fluorescent marker secreted into the medium was reduced by growth at 18 degrees C in buffered defined medium in the presence of sorbitol. Secondary screens included immunoblotting for GFP, fluorescence emission spectra, cell surface fluorescence, and cell integrity. Of 167 mutants deleted for genes affecting cell wall biogenesis or structure, eight showed consistent hyper-secretion of GFP relative to parental strain BY4743: tdh3 (glyceraldehyde-3-phosphate dehydrogenase), gda1 (guanosine diphosphatase), gpi13 and mcd4 (both ethanolamine phosphate-GPI-transferases), kre5 and kre1 (involved in synthesis of beta1,6 glucan), dcw1(implicated in GPI-CWP cross-linking to cell wall glucan), and cwp1 (a major cell wall protein). In addition, deletion of a number of genes caused decreased secretion of GFP. These results elucidate specific roles for specific genes in cell wall biogenesis, including differentiating among paralogous genes.

  9. On Background Independence

    CERN Document Server

    Anderson, Edward


    This paper concerns what Background Independence itself is (as opposed to some particular physical theory that is background independent). The notions presented mostly arose from a layer-by-layer analysis of the facets of the Problem of Time in Quantum Gravity. Part of this coincides with two relational postulates which are thus identified as classical precursors of two of the facets of the Problem of Time. These are furthemore tied to the forms of each of the GR Hamiltonian and momentum constraints. Other aspects of Background Independence include the algebraic closure of these constraints, expressing physics in terms of beables, foliation independence as implemented by refoliation invariance, the reconstruction of spacetime from space. The final picture is that Background Independence - a philosophically desirable and physically implementable feature for a theory to have - has the facets of the Problem of Time among its consequences. Thus these arise naturally and are problems to be resolved, as opposed to ...

  10. On-site tests to estimate aquifer permeability of drainage area of south caisson anchorage construction of Taizhou Bridge

    Institute of Scientific and Technical Information of China (English)

    Feng Zhaoxiang; Zhao Yanrong


    During the construction of the south caisson anchorage of Taizhou Bridge, the drainage area is located in the lower reaches of the Yangtze River and the permeability of stratums there is considerable. In order to maintain progress and guarantee safety during the sinking of the caisson, water should be drained in the initial period. Subsequently, detailed information about the aquifer permeability is required to make sure that the drainage will proceed successfully,which consequently necessitates the on-site estimation of the aquifer permeability in the drainage area. Therefore, the traditional pumping test and slug test are implemented respectively on site. The comparison of computational results of these two tests indicates that they are consistent overall. Notwithstanding, as slug test can be conducted with portable facilities in a short time and the manipulation is easy and few people need to be involved, the advantages of slug test is conspicuous compared with the traditional pumping test. It could be speculated that slug test will gain a prevalent application in the measurement of aquifer permeability in the future.

  11. The gamma secretase inhibitor MRK-003 attenuates pancreatic cancer growth in preclinical models (United States)

    Mizuma, Masamichi; Rasheed, Zeshaan A.; Yabuuchi, Shinichi; Omura, Noriyuki; Campbell, Nathaniel R.; de Wilde, Roeland F.; De Oliveira, Elizabeth; Zhang, Qing; Puig, Oscar; Matsui, William; Hidalgo, Manuel; Maitra, Anirban; Rajeshkumar, NV


    Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy, with most patients facing an adverse clinical outcome. Aberrant Notch pathway activation has been implicated in the initiation and progression of PDAC, specifically the aggressive phenotype of the disease. We used a panel of human PDAC cell lines, as well as patient-derived PDAC xenografts to determine whether pharmacological targeting of Notch pathway could inhibit PDAC growth and potentiate gemcitabine sensitivity. MRK-003, a potent and selective γ-secretase inhibitor, treatment is effective against PDAC as evidenced by the down-regulation of nuclear Notch1 intracellular domain (N1ICD), inhibition of anchorage independent growth, and reduction of tumor-initiating cells capable of extensive self-renewal. Pre-treatment of PDAC cells with MRK-003 in cell culture significantly inhibited the subsequent engraftment in immunocompromised mice. MRK-003 monotherapy significantly blocked tumor growth in 5 of 9 (56%) PDAC xenografts. A combination of MRK-003 and gemcitabine showed enhanced antitumor effects compared to gemcitabine in 4 of 9 (44%) PDAC xenografts, reduced tumor cell proliferation and induced both apoptosis and intra-tumoral necrosis. Gene expression analysis of untreated tumors indicated that up-regulation of nuclear factor kappa B (NFκB) pathway components were predictive of sensitivity to MRK-003, while up-regulation in B-cell receptor (BCR) signaling and nuclear factor erythroid-derived 2-like 2 (NRF2) pathway correlated with response to the combination of MRK-003 with gemcitabine. Our findings strengthen the rationale for small molecule inhibition of Notch signaling as a therapeutic strategy in PDAC. PMID:22752426

  12. LINE-1 ORF-1p functions as a novel HGF/ETS-1 signaling pathway co-activator and promotes the growth of MDA-MB-231 cell. (United States)

    Yang, Qian; Feng, Fan; Zhang, Fan; Wang, Chunping; Lu, Yinying; Gao, Xudong; Zhu, Yunfeng; Yang, Yongping


    Long interspersed nucleotide element (LINE)-1 ORF-1p is encoded by the human pro-oncogene LINE-1. It is involved in the development and progression of several human carcinomas, such as hepatocellular carcinoma and lung and breast cancers. The hepatocyte growth factor (HGF)/ETS-1 signaling pathway is involved in regulation of cancer cell proliferation, metastasis and invasion. The biological function of the interaction between LINE-1 ORF-1p and the HGF/ETS-1 signaling pathway in regulation of human breast cancer proliferation remains largely unknown. Here, we showed that LINE-1 ORF-1p enhanced ETS-1 transcriptional activity and increased expression of downstream genes of ETS-1. Interaction between ETS-1 and LINE-1 ORF-1p was identified by immunoprecipitation assays. LINE-1 ORF-1p modulated ETS-1 activity through cytoplasm/nucleus translocation and recruitment to the ETS-1 binding element in the MMP1 gene promoter. We also showed that LINE-1 ORF-1p promoted proliferation and anchorage-independent growth of MDA-MB-231 breast cancer cells. By investigating a novel role of the LINE-1 ORF-1p in the HGF/ETS-1 signaling pathway and MDA-MB-231 cells, we demonstrated that LINE-1 ORF-1p may be a novel ETS-1 coactivator and molecular target for therapy of human triple negative breast cancer. © 2013.

  13. Downregulation of Cyclophilin A by siRNA diminishes non-small cell lung cancer cell growth and metastasis via the regulation of matrix metallopeptidase 9

    Directory of Open Access Journals (Sweden)

    Qian Zhe


    Full Text Available Abstract Background Cyclophilin A (CypA is a cytosolic protein possessing peptidyl-prolyl isomerase activity that was recently reported to be overexpressed in several cancers. Here, we explored the biology and molecular mechanism of CypA in non-small cell lung cancer (NSCLC. Methods The expression of CypA in human NSCLC cell lines was detected by real-time reverse transcription PCR. The RNA interference-mediated knockdown of CypA was established in two NSCLC cell lines (95C and A549. 239836 CypA inhibitor was also used to suppress CypA activity. Tumorigenesis was assessed based on cellular proliferation, colony formation assays, and anchorage-independent growth assays; metastasis was assessed based on wound healing and transwell assays. Results Suppression of CypA expression inhibited the cell growth and colony formation of A549 and 95C cells. CypA knockdown resulted in the inhibition of cell motility and invasion. Significantly, we show for the first time that CypA increased NSCLC cell invasion by regulating the activity of secreted matrix metallopeptidase 9 (MMP9. Likewise, suppression of CypA with 239836 CypA inhibitor decreased cell proliferation and MMP9 activity. Conclusions The suppression of CypA expression was correlated with decreased NSCLC cell tumorigenesis and metastasis.

  14. Probabilistic conditional independence structures

    CERN Document Server

    Studeny, Milan


    Probabilistic Conditional Independence Structures provides the mathematical description of probabilistic conditional independence structures; the author uses non-graphical methods of their description, and takes an algebraic approach.The monograph presents the methods of structural imsets and supermodular functions, and deals with independence implication and equivalence of structural imsets.Motivation, mathematical foundations and areas of application are included, and a rough overview of graphical methods is also given.In particular, the author has been careful to use suitable terminology, and presents the work so that it will be understood by both statisticians, and by researchers in artificial intelligence.The necessary elementary mathematical notions are recalled in an appendix.

  15. Zakorzenienie umysłu w obiektach abstrakcyjnych (The Mind's Anchorage in Abstract Objects

    Directory of Open Access Journals (Sweden)

    Robert Piłat


    Full Text Available Some features of human linguistic competence make one to reconsider the Fregean notion of modes of presentation, which were supposed to correspond to senses of words. Especially two linguistic phenomena invite such a reflection: (1 generalized reports about people`s beliefs, like "Everybody thinks that p"; (2 semantic relations (like synonymy between empty names (proper or general. In the analysis of belief reports I am referring to studies by Edward Zalta; in the analysis of empty names I am drawing on Jerrold Katz and Georges Rey`s accounts. The three entirely independent inquiries seem to support the claim, that Fregean senses (understood as the modes of presentation presuppose the existence of abstract individuals and properties, which are intuitively apprehend by the speakers. It leads to certain conclusion about the nature of the human mind. In this article I am arguing that to the extent determined by the analyzed phenomena, human mind is in part an abstract entity - it incorporates - as its parts - the abstract entities though which it is referring to itself. This reference to oneself takes place in virtue of possessing ones own thoughts. Possessing thoughts is quite different from having experiences or more generally, psychological states. It requires that a subject is related to certain abstract objects. Although I do not believe that this claim amounts to some sort of spiritualism, I do believe that it imposes rather serious constraint on naturalistic accounts of the mind. This view is committed to rather strong form of emergentism or even to some kind of interactive dualism about the mind.

  16. Casein kinase 2α regulates glioblastoma brain tumor-initiating cell growth through the β-catenin pathway. (United States)

    Nitta, R T; Gholamin, S; Feroze, A H; Agarwal, M; Cheshier, S H; Mitra, S S; Li, G


    Glioblastoma (GBM) is the most common and fatal primary brain tumor in humans, and it is essential that new and better therapies are developed to treat this disease. Previous research suggests that casein kinase 2 (CK2) may be a promising therapeutic target for GBMs. CK2 has enhanced expression or activity in numerous cancers, including GBM, and it has been demonstrated that inhibitors of CK2 regressed tumor growth in GBM xenograft mouse models. Our studies demonstrate that the CK2 subunit, CK2α, is overexpressed in and has an important role in regulating brain tumor-initiating cells (BTIC) in GBM. Initial studies showed that two GBM cell lines (U87-MG and U138) transduced with CK2α had enhanced proliferation and anchorage-independent growth. Inhibition of CKα using siRNA or small-molecule inhibitors (TBBz, CX-4945) reduced cell growth, decreased tumor size, and increased survival rates in GBM xenograft mouse models. We also verified that inhibition of CK2α decreased the activity of a well-known GBM-initiating cell regulator, β-catenin. Loss of CK2α decreased two β-catenin-regulated genes that are involved in GBM-initiating cell growth, OCT4 and NANOG. To determine the importance of CK2α in GBM stem cell maintenance, we reduced CK2α activity in primary GBM samples and tumor spheres derived from GBM patients. We discovered that loss of CK2α activity reduced the sphere-forming capacity of BTIC and decreased numerous GBM stem cell markers, including CD133, CD90, CD49f and A2B5. Our study suggests that CK2α is involved in GBM tumorigenesis by maintaining BTIC through the regulation of β-catenin.

  17. Althaea rosea Cavanil and Plantago major L. suppress neoplastic cell transformation through the inhibition of epidermal growth factor receptor kinase. (United States)

    Choi, Eun-Sun; Cho, Sung-Dae; Shin, Ji-Ae; Kwon, Ki Han; Cho, Nam-Pyo; Shim, Jung-Hyun


    For thousands of years in Asia, Althaea rosea Cavanil (ARC) and Plantago major L. (PML) have been used as powerful non-toxic therapeutic agents that inhibit inflammation. However, the anticancer mechanisms and molecular targets of ARC and PML are poorly understood, particularly in epidermal growth factor (EGF)-induced neoplastic cell transformation. The aim of this study was to evaluate the chemopreventive effects and mechanisms of the methanol extracts from ARC (MARC) and PML (MPML) in EGF-induced neoplastic cell transformation of JB6 P+ mouse epidermal cells using an MTS assay, anchorage-independent cell transformation assay and western blotting. Our results showed that MARC and MPML significantly suppressed neoplastic cell transformation by inhibiting the kinase activity of the EGF receptor (EGFR). The activation of EGFR by EGF was suppressed by MARC and MPML treatment in EGFR(+/+) cells, but not in EGFR(-/-) cells. In addition, MARC and MPML inhibited EGF-induced cell proliferation in EGFR-expressing murine embryonic fibroblasts (EGFR(+/+)). These results strongly indicate that EGFR targeting by MARC and MPML may be a good strategy for chemopreventive or chemotherapeutic applications.

  18. Breast cancer oestrogen independence mediated by BCAR1 or BCAR3 genes is transmitted through mechanisms distinct from the oestrogen receptor signalling pathway or the epidermal growth factor receptor signalling pathway.

    NARCIS (Netherlands)

    L.C.J. Dorssers (Lambert); A. Brinkman (Arend); J. Veldscholte (Jos); M. Smid (Marcel); K.J. Dechering (Koen); A.J. van Agthoven (Ton)


    textabstractINTRODUCTION: Tamoxifen is effective for endocrine treatment of oestrogen receptor-positive breast cancers but ultimately fails due to the development of resistance. A functional screen in human breast cancer cells identified two BCAR genes causing oestrogen-independent proliferation. Th

  19. Electric-field-enhanced nutrient consumption in dielectric biomaterials that contain anchorage-dependent cells. (United States)

    Belfiore, Laurence A; Floren, Michael L; Belfiore, Carol J


    This research contribution addresses electric-field stimulation of intra-tissue mass transfer and cell proliferation in viscoelastic biomaterials. The unsteady state reaction-diffusion equation is solved according to the von Kármán-Pohlhausen integral method of boundary layer analysis when nutrient consumption and tissue regeneration occur in response to harmonic electric potential differences across a parallel-plate capacitor in a dielectric-sandwich configuration. The partial differential mass balance with diffusion and electro-kinetic consumption contains the Damköhler (Λ(2)) and Deborah (De) numbers. Zero-field and electric-field-sensitive Damköhler numbers affect nutrient boundary layer growth. Diagonal elements of the 2nd-rank diffusion tensor are enhanced in the presence of weak electric fields, in agreement with the formalism of equilibrium and nonequilibrium thermodynamics. Induced dipole polarization density within viscoelastic biomaterials is calculated via the real and imaginary components of the complex dielectric constant, according to the Debye equation, to quantify electro-kinetic stimulation. Rates of nutrient consumption under zero-field conditions are described by third-order kinetics that include local mass densities of nutrients, oxygen, and attached cells. Thinner nutrient boundary layers are stabilized at shorter dimensionless diffusion times when the zero-field intra-tissue Damköhler number increases above its initial-condition-sensitive critical value [i.e., {Λ(2)(zero-field)}(critical)≥53, see Eq. (23)], such that the biomaterial core is starved of essential ingredients required for successful proliferation. When tissue regeneration occurs above the critical electric-field-sensitive intra-tissue Damköhler number, the electro-kinetic contribution to nutrient consumption cannot be neglected. The critical electric-field-sensitive intra-tissue Damköhler number is proportional to the Deborah number.

  20. Efficacy of transpalatal arch as an anchorage reinforcing unit during orthodontic space closure: A three-dimensional finite element study

    Directory of Open Access Journals (Sweden)

    Vishal Shrishail Kudagi


    Full Text Available Background and Objectives: Connecting the contralateral upper molars by means of a transpalatal arch (TPA is thought to decrease the tendency of the molars to move mesially in response to orthodontic force (i.e., provide orthodontic anchorage. This study was hence conducted to investigate the effects of the TPA on the displacement of the molars and stresses generated in the periodontium during orthodontic tooth movement using the finite element method (FEM. Materials and Methods: A three-dimensional (3D model was generated using medical modeling software (Mimics using the computed tomography slice images of the skull which were obtained at a slice thickness of 1 mm. From this, the finite element model was built using HyperMesh and analysis was performed using PATRAN software (MSC Software Corporation, 4675 MacArthur Court, Newport Beach, California 92660. The 3D finite element models were fabricated in two versions such as maxillary first molars including their associated periodontal ligament and alveolar bone one with TPA and another without TPA. Both were subjected to orthodontic forces, and the resultant stress patterns and displacements between the models with and without TPA were determined. Results: The stress and displacement plots in this study failed to show any significant differences in stress and displacement within the periodontium of molars, between the two models – one with TPA and the other without, in response to the orthodontic force. Interpretation and Conclusion: The results of the current finite element analysis, therefore, suggest that the presence of a TPA brings about no change in the initial dental and periodontal stress distribution and displacement.

  1. Improved bone anchorage of hydroxypatite coated implants compared with tricalcium-phosphate coated implants in trabecular bone in dogs. (United States)

    Lind, M; Overgaard, S; Bünger, C; Søballe, K


    Tricalcium phosphate (TCP) and hydroxyapatite (HA) ceramic coatings are bioactive coatings that have been shown to stimulate bone apposition onto ceramic-coated implants. TCP and HA ceramics have well-documented differences in physical properties, but both types of ceramics are used for stimulation of bone ongrowth to cementless endo-prosthetic components clinically. However, little is known about the difference in osteoconductive properties between these coatings when inserted into trabecular bone in a controlled experimental situation. Unloaded cylindrical gritblasted titanium (Ti-6A1-4V) implants (6 x 10 mm) coated with either hydroxyapatite (HA) or tricalcium phosphate (TCP) ceramic were inserted into the proximal humerus of 20 skeletally mature dogs. The implants were initially surrounded by a 2 mm gap. Each animal received one HA-coated implant and one TCP-coated implant. All dogs were sacrificed 6 weeks after surgery. Results were evaluated by histomorphometry and mechanical push-out test. Push-out tests demonstrated that HA-coated implants were 10-fold stronger fixated in comparison to TCP-coated implant. Bone ongrowth was significantly higher for HA-coated implants compared to TCP-coated implants. Bone volume in the gap showed a tendency to less bone volume around HA-coated implants compared to TCP-coated implants but this difference was insignificant. As expected almost all of the TCP coating were resorbed after 6 weeks and almost none of the HA coating. HA-coated implants with a grit-blasted surface provide a favorable early mechanical implant anchorage most likely due to superior ceramic stability compared to TCP-coated implants.

  2. Laser-Modified Surface Enhances Osseointegration and Biomechanical Anchorage of Commercially Pure Titanium Implants for Bone-Anchored Hearing Systems. (United States)

    Shah, Furqan A; Johansson, Martin L; Omar, Omar; Simonsson, Hanna; Palmquist, Anders; Thomsen, Peter


    Osseointegrated implants inserted in the temporal bone are a vital component of bone-anchored hearing systems (BAHS). Despite low implant failure levels, early loading protocols and simplified procedures necessitate the application of implants which promote bone formation, bone bonding and biomechanical stability. Here, screw-shaped, commercially pure titanium implants were selectively laser ablated within the thread valley using an Nd:YAG laser to produce a microtopography with a superimposed nanotexture and a thickened surface oxide layer. State-of-the-art machined implants served as controls. After eight weeks' implantation in rabbit tibiae, resonance frequency analysis (RFA) values increased from insertion to retrieval for both implant types, while removal torque (RTQ) measurements showed 153% higher biomechanical anchorage of the laser-modified implants. Comparably high bone area (BA) and bone-implant contact (BIC) were recorded for both implant types but with distinctly different failure patterns following biomechanical testing. Fracture lines appeared within the bone ~30-50 μm from the laser-modified surface, while separation occurred at the bone-implant interface for the machined surface. Strong correlations were found between RTQ and BIC and between RFA at retrieval and BA. In the endosteal threads, where all the bone had formed de novo, the extracellular matrix composition, the mineralised bone area and osteocyte densities were comparable for the two types of implant. Using resin cast etching, osteocyte canaliculi were observed directly approaching the laser-modified implant surface. Transmission electron microscopy showed canaliculi in close proximity to the laser-modified surface, in addition to a highly ordered arrangement of collagen fibrils aligned parallel to the implant surface contour. It is concluded that the physico-chemical surface properties of laser-modified surfaces (thicker oxide, micro- and nanoscale texture) promote bone bonding which

  3. A Component-Based Study of the Effect of Diameter on Bond and Anchorage Characteristics of Blind-Bolted Connections.

    Directory of Open Access Journals (Sweden)

    Muhammad Nasir Amin

    Full Text Available Structural hollow sections are gaining worldwide importance due to their structural and architectural advantages over open steel sections. The only obstacle to their use is their connection with other structural members. To overcome the obstacle of tightening the bolt from one side has given birth to the concept of blind bolts. Blind bolts, being the practical solution to the connection hindrance for the use of hollow and concrete filled hollow sections play a vital role. Flowdrill, the Huck High Strength Blind Bolt and the Lindapter Hollobolt are the well-known commercially available blind bolts. Although the development of blind bolts has largely resolved this issue, the use of structural hollow sections remains limited to shear resistance. Therefore, a new modified version of the blind bolt, known as the "Extended Hollo-Bolt" (EHB due to its enhanced capacity for bonding with concrete, can overcome the issue of low moment resistance capacity associated with blind-bolted connections. The load transfer mechanism of this recently developed blind bolt remains unclear, however. This study uses a parametric approach to characterising the EHB, using diameter as the variable parameter. Stiffness and load-carrying capacity were evaluated at two different bolt sizes. To investigate the load transfer mechanism, a component-based study of the bond and anchorage characteristics was performed by breaking down the EHB into its components. The results of the study provide insight into the load transfer mechanism of the blind bolt in question. The proposed component-based model was validated by a spring model, through which the stiffness of the EHB was compared to that of its components combined. The combined stiffness of the components was found to be roughly equivalent to that of the EHB as a whole, validating the use of this component-based approach.

  4. Independent technical review, handbook

    Energy Technology Data Exchange (ETDEWEB)


    Purpose Provide an independent engineering review of the major projects being funded by the Department of Energy, Office of Environmental Restoration and Waste Management. The independent engineering review will address questions of whether the engineering practice is sufficiently developed to a point where a major project can be executed without significant technical problems. The independent review will focus on questions related to: (1) Adequacy of development of the technical base of understanding; (2) Status of development and availability of technology among the various alternatives; (3) Status and availability of the industrial infrastructure to support project design, equipment fabrication, facility construction, and process and program/project operation; (4) Adequacy of the design effort to provide a sound foundation to support execution of project; (5) Ability of the organization to fully integrate the system, and direct, manage, and control the execution of a complex major project.

  5. Distro’: Independent Creativity for Independent Industr

    Directory of Open Access Journals (Sweden)

    Wiwik Sri Wulandari


    Full Text Available To shortened this introduction, ‘Distro’ is one of cultural phenomenon in theyoung generation nowadays. The word of ‘Distro’ is the shortened of DistributionOutlet. The phenomenon of ‘Distro’ has been some kind of new trends inproducing and distributing creative design products of goods amongst theyoungsters independently, in an independence industry that open for challengingand competitiveness for everyone. This field research has been done in the city ofYogyakarta, reknown as the second city in creative design products after the cityof Bandung. Yogyakarta is welknown as the students’ city as well as the capital cityof culture of Indonesia. As a students’ city it is normal that Yogyakarta is growingin numbers of young people who pursued to study here and enriched the cultureof the city to become more multicultural and the varieties of pluralism as well.This sociocultural phenomenon not only brought some dynamic changing tosociety, economy and cultural life of the city, but also social problems that needsto be overcome. My first research question then is about how the existence of‘Distro’ in Yogyakarta can be a positive answer for social problems that may arisesfrom the hegemony of globalization markets domestically? My second questionis how the creative product designs are being made and distributed creatively inindependent industry? Lastly, my third question is dealling with the genres ofthe design products and how it can be a new trend in art expression? ‘Distro’ is aproduct of culture and it is also creating cultural change in some aspects of the lifeof the youngsters who are ‘Distro’ enthusiasts. ‘Distro’ phenomenon basically is anoffensive to the hegemony of internationally branded product design which turnsto become more over-dominated to the domestic markets and industry and thus,‘Distro’ has the spirit of survival whilts at the same time producing opportunity ofenterpreneurship

  6. Symmetry implies independence

    CERN Document Server

    Renner, R


    Given a quantum system consisting of many parts, we show that symmetry of the system's state, i.e., invariance under swappings of the subsystems, implies that almost all of its parts are virtually identical and independent of each other. This result generalises de Finetti's classical representation theorem for infinitely exchangeable sequences of random variables as well as its quantum-mechanical analogue. It has applications in various areas of physics as well as information theory and cryptography. For example, in experimental physics, one typically collects data by running a certain experiment many times, assuming that the individual runs are mutually independent. Our result can be used to justify this assumption.


    Institute of Scientific and Technical Information of China (English)

    尤春安; 战玉宝; 刘秋媛; 孙琳琳; 王开彬


    Based on the calculating pattern of pulling prestressed anchorage body out from the base,the anchorage section can be divided into elastic region,plastic slide region and debonding region after analyzing the deformation and the damage process of the interface layer between anchorage body and grouting material,and the interfacial layer model for anchorage body and rock and soil mass is established.The theoretical solution of interfacial stress distribution was deduced by adopting the flow rule which associates with Coulomb condition.At the same time,a kind of new interface element model with properties of dilatancy and slippage is constructed; and interfacial stress distribution is calculated by two ways of numerical simulation and theoretical solution to verify the correctness of each other,so as to provide a new theoretical basis to calculate,analyze and design anchorage bodies.The results indicate that the main mechanical region is plastic slide region.So the plastic slippage state is the main state which the anchorage body usually in,so our researching and designing should be based on this state.In order to improve the anchoring force,we should improve maximum shear stress and extend the range of slip regime before the slip regime entering the debonding state.%基于预应力锚索锚固体从岩土体中拔出计算模式,通过锚固体与灌浆材料的界面界面层变形-破坏过程分析,将锚固段分为弹性区、塑性滑移区和脱黏区,建立锚固体-岩土体界面力学模型,采用与Coulomb条件关连的流动法则,导出界面应力分布的理论解;同时,构造具有剪胀和滑移特性的新型有限元界面单元,采用数值模拟的方法与界面应力分布的理论解进行相互验证,为锚固体受力的计算、分析与锚固体的设计提供理论依据.分析表明,锚固体的弹性区和脱黏区的受力较小,主要受力部分是塑性滑移区.因此,锚固体荷载的主要工况是塑性滑移状态,在研究

  8. Intracellular Transactivation of Epidermal Growth Factor Receptor by alpha(1A)-Adrenoceptor Is Mediated by Phosphatidylinositol 3-Kinase Independently of Activation of Extracellular Signal Regulated Kinases 1/2 and Serine-Threonine Kinases in Chinese Hamster Ovary Cells

    NARCIS (Netherlands)

    Ulu, Nadir; Henning, Robert H.; Guner, Sahika; Zoto, Teuta; Duman-Dalkilic, Basak; Duin, Marry; Gurdal, Hakan


    Transactivation of epidermal growth factor receptor (EGFR) by alpha(1)-adrenoceptor (alpha(1)-AR) is implicated in contraction and hypertrophy of vascular smooth muscle (VSM). We examine whether all alpha(1)-AR subtypes transactivate EGFR and explore the mechanism of transactivation. Chinese hamster

  9. The Critical Independence Number and an Independence Decomposition

    CERN Document Server

    Larson, Craig Eric


    An independent set $I_c$ is a \\textit{critical independent set} if $|I_c| - |N(I_c)| \\geq |J| - |N(J)|$, for any independent set $J$. The \\textit{critical independence number} of a graph is the cardinality of a maximum critical independent set. This number is a lower bound for the independence number and can be computed in polynomial-time. Any graph can be decomposed into two subgraphs where the independence number of one subgraph equals its critical independence number, where the critical independence number of the other subgraph is zero, and where the sum of the independence numbers of the subgraphs is the independence number of the graph. A proof of a conjecture of Graffiti.pc yields a new characterization of K\\"{o}nig-Egervary graphs: these are exactly the graphs whose independence and critical independence numbers are equal.

  10. Orthodontic treatment of impacted teeth with implant anchorage%运用微型种植体支抗矫治埋伏阻生牙

    Institute of Scientific and Technical Information of China (English)

    张敏; 张立亚; 刘佳


    Objective To investigate effectiveness and efficiency of impacted teeth correction with implant anchorage.Methods Eight impacted teeth in six patients were corrected with implant anchorage after surgical exposure.Tooth mobility and pulp vitality were evaluated.Dental radiographs were taken before and after treatment.Results Good results were obtained and the impacted teeth were erupted within 3 ~ 5 months after orthodontic traction.The pulp of the teeth was vital Conclusions The implant anchorage could be used in the treatment of impacted teeth.%目的 初步分析运用种植支抗牵引埋伏牙的临床效果,探讨正畸治疗中选择种植支抗牵引埋伏牙的适应证及该项治疗的特点.方法 对6例埋伏牙患者的8颗埋伏牙运用种植支抗进行牵引治疗,牵引后对牙齿的松动度、牙髓活力等各项临床指标进行检查,并摄术前术后曲面断层片对牵引效果进行观察.结果 6例患者经3~5个月的牵引后埋伏牙萌出,牙髓活力正常,未发现牙根吸收.与以往的方法相比,运用种植支抗牵引埋伏牙支抗充足,患者不适感降低.结论 运用种植支抗牵引埋伏牙为埋伏牙牵引治疗提供了一种方法选择.

  11. Independent School Administration. (United States)

    Springer, E. Laurence

    This book deals with the management of privately supported schools and offers guidelines on how these schools might be operated more effectively and economically. The discussions and conclusions are based on observations and data from case studies of independent school operations. The subjects discussed include the role and organization of…

  12. Independence in appearance

    DEFF Research Database (Denmark)

    Warming-Rasmussen, Bent; Quick, Reiner; Liempd, Dennis van


    article presents research contributions to the question whether the auditor is to continue to provide both audit and non-audit services (NAS) to an audit client. Research results show that this double function for the same audit client is a problem for stakeholders' confidence in auditor independence...

  13. Thermal Pollution Mathematical Model. Volume 6: Verification of Three-Dimensional Free-Surface Model at Anclote Anchorage. [environment impact of thermal discharges from power plants (United States)

    Lee, S. S.; Sengupta, S.; Tuann, S. Y.; Lee, C. R.


    The free-surface model presented is for tidal estuaries and coastal regions where ambient tidal forces play an important role in the dispersal of heated water. The model is time dependent, three dimensional, and can handle irregular bottom topography. The vertical stretching coordinate is adopted for better treatment of kinematic condition at the water surface. The results include surface elevation, velocity, and temperature. The model was verified at the Anclote Anchorage site of Florida Power Company. Two data bases at four tidal stages for winter and summer conditions were used to verify the model. Differences between measured and predicted temperatures are on an average of less than 1 C.

  14. Effects of the earthquake of March 27, 1964, on the Eklutna Hydroelectric Project, Anchorage, Alaska, with a section on television examination of earthquake damage to underground communication and electrical systems in Anchorage: Chapter A in The Alaska earthquake, March 27, 1964: effects on transportation, communications, and utilities (United States)

    Logan, Malcolm H.; with a section on Television Examination of Earthquake Damage to Underground Communication and Electrical Systems in Anchorage by Burton, Lynn R.


    The March 27, 1964, Alaska earthquake and its associated aftershocks caused damage requiring several million dollars worth of repair to the Eklwtna Hydroelectric Project, 34 miles northeast of Anchorage. Electric service from the Eklutna powerplant was interrupted during the early phase of the March 27 earthquake, built was restored (intermittently) until May 9,1964, when the plant was closed for inspection and repair. Water for Eklutna project is transported from Eklutna Lake to the powerplant at tidewater on Knik Arm of Cook Inlet by an underwater intake connected to a 4.46-mile tunnel penstock. The primary damage caused by the earthquake was 1at the intake structure in Eklutna Lake. No damage to the power tunnel was observed. The piles-supported powerplant and appurtenant structures, Anchorage and Palmer substations, and the transmission lines suffered minor dammage. Most damage occurred to facilities constructed on un-consolidated sediments and overburden which densified and subsided during the earthquake. Structures built on bedrock experienced little or no damage. Underground communication and electrical systems in Anchorage were examined with a small-diameter television camera to locate damaged areas requiring repair. Most of the damage was concentrated at or near valley slopes. Those parts of the systems within the major slide areas of the city were destroyed.

  15. MicroRNA let-7c is downregulated in prostate cancer and suppresses prostate cancer growth.

    Directory of Open Access Journals (Sweden)

    Nagalakshmi Nadiminty

    Full Text Available PURPOSE: Prostate cancer (PCa is characterized by deregulated expression of several tumor suppressor or oncogenic miRNAs. The objective of this study was the identification and characterization of miR-let-7c as a potential tumor suppressor in PCa. EXPERIMENTAL DESIGN: Levels of expression of miR-let-7c were examined in human PCa cell lines and tissues using qRT-PCR and in situ hybridization. Let-7c was overexpressed or suppressed to assess the effects on the growth of human PCa cell lines. Lentiviral-mediated re-expression of let-7c was utilized to assess the effects on human PCa xenografts. RESULTS: We identified miR-let-7c as a potential tumor suppressor in PCa. Expression of let-7c is downregulated in castration-resistant prostate cancer (CRPC cells. Overexpression of let-7c decreased while downregulation of let-7c increased cell proliferation, clonogenicity and anchorage-independent growth of PCa cells in vitro. Suppression of let-7c expression enhanced the ability of androgen-sensitive PCa cells to grow in androgen-deprived conditions in vitro. Reconstitution of Let-7c by lentiviral-mediated intratumoral delivery significantly reduced tumor burden in xenografts of human PCa cells. Furthermore, let-7c expression is downregulated in clinical PCa specimens compared to their matched benign tissues, while the expression of Lin28, a master regulator of let-7 miRNA processing, is upregulated in clinical PCa specimens. CONCLUSIONS: These results demonstrate that microRNA let-7c is downregulated in PCa and functions as a tumor suppressor, and is a potential therapeutic target for PCa.

  16. Treatment of Class II malocclusion with bialveolar protrusion by means of unusual extractions and anchorage mini-implant

    Directory of Open Access Journals (Sweden)

    Jong-Moon Chae


    Full Text Available INTRODUCTION: Patients with dental Class II bialveolar protrusion are generally treated by extracting the four first premolars or two first and two second premolars, and retracting the anterior teeth. This case report describes the treatment of an adult patient with bialveolar protrusion, a Class II canine and molar relationship, and lip protrusion. METHODS: In this patient, the maxillary right second molar (1.7 had to be extracted due to extensive caries. To create sufficient space to retract the anterior teeth, the maxillary right posterior teeth were distalized with a maxillary posterior mini-implant (1.2~1.3 mm in diameter, 10 mm long, which was placed into the maxillary tuberosity area and allowed an en masse retraction of the maxillary anterior teeth. RESULTS: Overall, mini-implant can provide anchorage to produce a good facial profile even without additional premolar extraction in cases of dental Class II bialveolar protrusion with the hopeless second molar. CONCLUSION: The total treatment period was 42 months and the results were acceptable for 34 months after debonding.INTRODUÇÃO: os pacientes com Classe II e biprotrusão alveolar são, geralmente, tratados com extração de quatro primeiros pré-molares ou dois primeiros e dois segundos pré-molares, e retração dos dentes anteriores. Este relato de caso descreve o tratamento de um paciente adulto com biprotrusão alveolar, relação de caninos e de molares em Classe II e protrusão labial. MÉTODOS: nesse paciente, o segundo molar superior direito precisou ser extraído devido a cáries extensas. Para criar espaço suficiente para retração dos dentes anteriores, os dentes posterossuperiores direitos foram distalizados com um mini-implante posterossuperior (1,2 ~ 1,3mm de diâmetro, 10mm de comprimento, que foi colocado na área da tuberosidade maxilar e permitiu uma retração em massa dos dentes anteriores. RESULTADOS: em geral, mini-implantes podem fornecer ancoragem para

  17. Quantum independent increment processes

    CERN Document Server

    Franz, Uwe


    This volume is the first of two volumes containing the revised and completed notes lectures given at the school "Quantum Independent Increment Processes: Structure and Applications to Physics". This school was held at the Alfried-Krupp-Wissenschaftskolleg in Greifswald during the period March 9 – 22, 2003, and supported by the Volkswagen Foundation. The school gave an introduction to current research on quantum independent increment processes aimed at graduate students and non-specialists working in classical and quantum probability, operator algebras, and mathematical physics. The present first volume contains the following lectures: "Lévy Processes in Euclidean Spaces and Groups" by David Applebaum, "Locally Compact Quantum Groups" by Johan Kustermans, "Quantum Stochastic Analysis" by J. Martin Lindsay, and "Dilations, Cocycles and Product Systems" by B.V. Rajarama Bhat.

  18. Field Independent Cosmic Evolution

    Directory of Open Access Journals (Sweden)

    Nayem Sk


    Full Text Available It has been shown earlier that Noether symmetry does not admit a form of corresponding to an action in which is coupled to scalar-tensor theory of gravity or even for pure theory of gravity taking anisotropic model into account. Here, we prove that theory of gravity does not admit Noether symmetry even if it is coupled to tachyonic field and considering a gauge in addition. To handle such a theory, a general conserved current has been constructed under a condition which decouples higher-order curvature part from the field part. This condition, in principle, solves for the scale-factor independently. Thus, cosmological evolution remains independent of the form of the chosen field, whether it is a scalar or a tachyon.


    Institute of Scientific and Technical Information of China (English)



    @@ Ⅰ. Introduction At present, in the college, English extensive reading class, most students are not used to being independent. They always ask the teacher to explain the passages sentence by sentence and they need a lot of time to use the dictionary. Yet, we should take the responsibility for the students by making clear the difference between intensive and extensive reading. The traditional teaching approaches pays more attention to the teacher-centered way;the teacher always plays a monodrama, and the teacher dominates the class. The students are lack initiative. Some students do not know where they could start from, and the others are short of fast-reading skills, always fixing their eyes on one word or one sentence. Under the new situation and new thinking, students should learn to be more independent.

  20. Bayesian Independent Component Analysis

    DEFF Research Database (Denmark)

    Winther, Ole; Petersen, Kaare Brandt


    In this paper we present an empirical Bayesian framework for independent component analysis. The framework provides estimates of the sources, the mixing matrix and the noise parameters, and is flexible with respect to choice of source prior and the number of sources and sensors. Inside the engine...... in a Matlab toolbox, is demonstrated for non-negative decompositions and compared with non-negative matrix factorization....

  1. Random Independence Systems (United States)


    Whitney provided a set of axioms for a structure commonly called i a matroid. Matroid theory (see ( Tutte , 19711, [Lawler, 19761) has applications to a wide...applicable in this case. On the other hand, there is no known efficient ( polynomial time) algorithm for constructing cliques of size 2 log n with...intersection. The problem of constructing a maximal independent set in the intersection of k matroids has a polynomial time (in tEl) algorithm [Lawler, 197

  2. 口周肌力在下颌支抗控制中的临床应用研究%Clinical application of perioral muscular forces in mandibular anchorage control

    Institute of Scientific and Technical Information of China (English)

    林汤毅; 许衍; 王震东; 李强


    目的 探讨口周肌力在下颌支抗控制中的应用.方法 临床上应用多曲不锈钢丝唇挡配合方丝弓固定矫治器对13例恒牙早期轻度牙列拥挤患者进行矫治,分析治疗前后支抗磨牙位置变化,观察支抗丧失情况.结果 利用口周肌力可以对支抗磨牙进行控制,防止支抗丧失.结论 可以在矫治过程中采用多曲唇挡来增强支抗.而且多曲唇挡制作简单,患者戴用舒适、隐蔽,容易获得患者的配合.%Objective To study the application of perioral muscular forces in the mandibular anchorage control in order to search a new approach of increasing the intro-oral anchorage. Methods Thirteen patients with mild crowding in permanent dentition were treated with edgewise appliance and multiloop lip bumper. The movement of anchorage molar in before and after treatment was recorded so as to observe the loss of anchorage. Results The loss of anchorage could be avoided through the application of perioral muscular forces. Conclusions The multiloop lip bumper can be applied to increase anchorage, which is easily fabricated, comfortable and hidden for patients.

  3. Anchorage in concrete construction

    CERN Document Server

    Eligehausen, Rolf; Silva, John F


    A comprehensive treatment of current fastening technology using inserts (anchor channels, headed stud), anchors (metal expansion anchor, undercut anchor, bonded anchor, concrete screw and plastic anchor) as well as power actuated fasteners in concrete. It describes in detail the fastening elements as well as their effects and load-bearing capacities in cracked and non-cracked concrete. It further focuses on corrosion behaviour, fire resistance and characteristics with earthquakes and shocks. It finishes off with the design of fastenings according to the European Technical Approval Guideline (ETAG 001), the Final Draft of the CEN Technical Specification 'Design of fastenings for use in concrete' and the American Standards ACI 318-05, Appendix D and ACI 349-01, Appendix B.

  4. DDX3, a DEAD box RNA helicase, is deregulated in hepatitis virus-associated hepatocellular carcinoma and is involved in cell growth control. (United States)

    Chang, P-C; Chi, C-W; Chau, G-Y; Li, F-Y; Tsai, Y-H; Wu, J-C; Wu Lee, Y-H


    Hepatocellular carcinoma (HCC) is one of the leading causes of cancer deaths worldwide and is highly correlated with hepatitis virus infection. Our previous report shows that a DEAD box RNA helicase, DDX3, is targeted and regulated by hepatitis C virus (HCV) core protein, which implicates the involvement of DDX3 in HCV-related HCC development. In this study, the potential role of DDX3 in hepatocarcinogenesis is investigated by examining its expression in surgically excised human HCC specimens. Here we report the differential deregulation of DDX3 expression in hepatitis virus-associated HCC. A significant downregulation of DDX3 expression is found in HCCs from hepatitis B virus (HBV)-positive patients, but not from HCV-positive ones, compared to the corresponding nontumor tissues. The expression of DDX3 is differentially regulated by the gender and, moreover, there is a tendency that the downregulation of DDX3 expression in HCCs is more frequent in males than in females. Genetic knockdown of DDX3 with small interfering RNAs (siRNA) in a nontransformed mouse fibroblast cell line, NIH-3T3, results in a premature entry to S phase and an enhancement of cell growth. This enhanced cell cycle progression is linked to the upregulation of cyclin D1 and the downregulation of p21(WAF1) in the DDX3 knockdown cells. In addition, constitutive reduction of DDX3 expression increases the resistance of NIH-3T3 cells to serum depletion-induced apoptosis and enhances the ras-induced anchorage-independent growth, indicating the involvement of DDX3 in cell growth control. These findings together with the previous study suggest that the deregulation of DDX3, a DEAD box RNA helicase with cell growth-regulatory functions, is involved in HBV- and HCV-associated pathogenesis.

  5. Reciprocal interactions between Beta1-integrin and epidermal growth factor in three-dimensional basement membrane breast cultures: A different perspective in epithelial biology

    Energy Technology Data Exchange (ETDEWEB)

    Wang, F.; Weaver, V.M.; Petersen, O.W.; Larabell, C.A.; Dedhar, S.; Briand, P.; Lupu, R.; Bissell, M.J.


    Anchorage and growth factor independence are cardinal features of the transformed phenotype. Although it is logical that the two pathways must be coregulated in normal tissues to maintain homeostasis, this has not been demonstrated directly. We showed previously that down-modulation of {beta}1-integrin signaling reverted the malignant behavior of a human breast tumor cell line (T4-2) derived from phenotypically normal cells (HMT-3522) and led to growth arrest in a threedimensional (3D) basement membrane assay in which the cells formed tissue-like acini (14). Here, we show that there is a bidirectional cross-modulation of {beta}1-integrin and epidermal growth factor receptor (EGFR) signaling via the mitogenactivated protein kinase (MAPK) pathway. The reciprocal modulation does not occur in monolayer (2D) cultures. Antibodymediated inhibition of either of these receptors in the tumor cells, or inhibition of MAPK kinase, induced a concomitant downregulation of both receptors, followed by growth-arrest and restoration of normal breast tissue morphogenesis. Crossmodulation and tissue morphogenesis were associated with attenuation of EGF-induced transient MAPK activation. To specifically test EGFR and {beta}1-integrin interdependency, EGFR was overexpressed in nonmalignant cells, leading to disruption of morphogenesis and a compensatory up-regulation of {beta}1-integrin expression, again only in 3D. Our results indicate that when breast cells are spatially organized as a result of contact with basement membrane, the signaling pathways become coupled and bidirectional. They further explain why breast cells fail to differentiate in monolayer cultures in which these events are mostly uncoupled. Moreover, in a subset of tumor cells in which these pathways are misregulated but functional, the cells could be 'normalized' by manipulating either pathway.

  6. IGF-IR promotes prostate cancer growth by stabilizing α5β1 integrin protein levels.

    Directory of Open Access Journals (Sweden)

    Aejaz Sayeed

    Full Text Available Dynamic crosstalk between growth factor receptors, cell adhesion molecules and extracellular matrix is essential for cancer cell migration and invasion. Integrins are transmembrane receptors that bind extracellular matrix proteins and enable cell adhesion and cytoskeletal organization. They also mediate signal transduction to regulate cell proliferation and survival. The type 1 insulin-like growth factor receptor (IGF-IR mediates tumor cell growth, adhesion and inhibition of apoptosis in several types of cancer. We have previously demonstrated that β1 integrins regulate anchorage-independent growth of prostate cancer (PrCa cells by regulating IGF-IR expression and androgen receptor-mediated transcriptional functions. Furthermore, we have recently reported that IGF-IR regulates the expression of β1 integrins in PrCa cells. We have dissected the mechanism through which IGF-IR regulates β1 integrin expression in PrCa. Here we report that IGF-IR is crucial for PrCa cell growth and that β1 integrins contribute to the regulation of proliferation by IGF-IR. We demonstrate that β1 integrin regulation by IGF-IR does not occur at the mRNA level. Exogenous expression of a CD4 - β1 integrin cytoplasmic domain chimera does not interfere with such regulation and fails to stabilize β1 integrin expression in the absence of IGF-IR. This appears to be due to the lack of interaction between the β1 cytoplasmic domain and IGF-IR. We demonstrate that IGF-IR stabilizes the β1 subunit by protecting it from proteasomal degradation. The α5 subunit, one of the binding partners of β1, is also downregulated along with β1 upon IGF-IR knockdown while no change is observed in the expression of the α2, α3, α4, α6 and α7 subunits. Our results reveal a crucial mechanistic role for the α5β1 integrin, downstream of IGF-IR, in regulating cancer growth.

  7. Independence among People with Disabilities: II. Personal Independence Profile. (United States)

    Nosek, Margaret A.; And Others


    Developed Personal Independence Profile (PIP) as an instrument to measure aspects of independence beyond physical and cognitive functioning in people with diverse disabilities. PIP was tested for reliability and validity with 185 subjects from 10 independent living centers. Findings suggest that the Personal Independence Profile measures the…

  8. Multi-modal exercise training and protein-pacing enhances physical performance adaptations independent of growth hormone and BDNF but may be dependent on IGF-1 in exercise-trained men. (United States)

    Ives, Stephen J; Norton, Chelsea; Miller, Vincent; Minicucci, Olivia; Robinson, Jake; O'Brien, Gabe; Escudero, Daniela; Paul, Maia; Sheridan, Caitlin; Curran, Kathryn; Rose, Kayla; Robinson, Nathaniel; He, Feng; Arciero, Paul J


    Protein-pacing (P; 5-6meals/day @ 2.0g/kgBW/day) and multi-mode exercise (RISE; resistance, interval, stretching, endurance) training (PRISE) improves muscular endurance, strength, power and arterial health in exercise-trained women. The current study extends these findings by examining PRISE on fitness, growth hormone (GH), insulin-like growth factor-1 (IGF-1), and brain-derived neurotrophic factor (BDNF) response, cardiometabolic health, and body composition in exercise-trained men. Twenty active males (>4daysexercise/week) completed either: PRISE (n=11) or RISE (5-6meals/day @ 1.0g/kgBW/day; n=9) for 12weeks. Muscular strength (1-repetition maximum bench and leg press, 1-RM BP, and 1-RM LP), endurance (sit-ups, SU; push-ups, PU), power (squat jump, SJ, and bench throw, BT), flexibility (sit-and-reach, SR), aerobic performance (5km cycling time-trial, TT), GH, IGF-1, BDNF, augmentation index, (AIx), and body composition, were assessed at weeks 0 (pre) and 13 (post). At baseline, no differences existed between groups except for GH (RISE, 230±13 vs. PRISE, 382±59pg/ml, pExercise-trained men consuming a P diet combined with multi-component exercise training (PRISE) enhance muscular power, strength, aerobic performance, and flexibility which are not likely related to GH or BDNF but possibly to IGF-1 response. Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  9. Prolyl hydroxylase 2 dependent and Von-Hippel-Lindau independent degradation of Hypoxia-inducible factor 1 and 2 alpha by selenium in clear cell renal cell carcinoma leads to tumor growth inhibition

    Directory of Open Access Journals (Sweden)

    Chintala Sreenivasulu


    Full Text Available Abstract Background Clear cell renal cell carcinoma (ccRCC accounts for more than 80% of the cases of renal cell carcinoma. In ccRCC deactivation of Von-Hippel-Lindau (VHL gene contributes to the constitutive expression of hypoxia inducible factors 1 and 2 alpha (HIF-α, transcriptional regulators of several genes involved in tumor angiogenesis, glycolysis and drug resistance. We have demonstrated inhibition of HIF-1α by Se-Methylselenocysteine (MSC via stabilization of prolyl hydroxylases 2 and 3 (PHDs and a significant therapeutic synergy when combined with chemotherapy. This study was initiated to investigate the expression of PHDs, HIF-α, and VEGF-A in selected solid cancers, the mechanism of HIF-α inhibition by MSC, and to document antitumor activity of MSC against human ccRCC xenografts. Methods Tissue microarrays of primary human cancer specimens (ccRCC, head & neck and colon were utilized to determine the incidence of PHD2/3, HIF-α, and VEGF-A by immunohistochemical methods. To investigate the mechanism(s of HIF-α inhibition by MSC, VHL mutated ccRCC cells RC2 (HIF-1α positive, 786–0 (HIF-2α positive and VHL wild type head & neck cancer cells FaDu (HIF-1α were utilized. PHD2 and VHL gene specific siRNA knockdown and inhibitors of PHD2 and proteasome were used to determine their role in the degradation of HIF-1α by MSC. Results We have demonstrated that ccRCC cells express low incidence of PHD2 (32%, undetectable PHD3, high incidence of HIF-α (92%, and low incidence of VEGF-A compared to head & neck and colon cancers. This laboratory was the first to identify MSC as a highly effective inhibitor of constitutively expressed HIF-α in ccRCC tumors. MSC did not inhibit HIF-1α protein synthesis, but facilitated its degradation. The use of gene knockdown and specific inhibitors confirmed that the inhibition of HIF-1α was PHD2 and proteasome dependent and VHL independent. The effects of MSC treatment on HIF-α were associated with

  10. The importance of board independence

    NARCIS (Netherlands)

    Zijl, N.J.M.


    Although the attributed importance of board independence is high, a clear definition of independence does not exist. Furthermore, the aim and consequences of independence are the subject of discussion and empirical evidence about the impact of independence is weak and disputable. Despite this lack o

  11. Hydrogen for transport in Denmark towards 2050. Contribution to electric-powered transport, growth, CO{sub 2} reduction and independence of fossil fuels; Brint til transport i Danmark frem mod 2050. Bidrag til elektrisk transport, vaekst, CO{sub 2} reduktion og fossil uafhaengighed. Baggrundsrapport. Endelig udgave

    Energy Technology Data Exchange (ETDEWEB)

    Wennike, F. (Hydrogen Link Danmark (Denmark)); Mortensgaard, A. (Brint and Braendselscelle Partnerskabet, Copenhagen (Denmark)); Sloth, M. (H2 Logic A/S, Herning (Denmark))


    Significant funding has been invested internationally in the development of hydrogen and fuel cells for the last 10 years, among others by the leading car makers. In Denmark alone businesses have, along with contributions from public programs, invested two billion DKK since 2001. The investments have helped to develop and mature hydrogen and fuel cells so that a deployment can be initiated from 2015. With the Danish government's new initiative, ''Our Energy'', which is targeted towards a switch to a fossil fuel-independent society in 2050, it is obvious that hydrogen is included as one of many technologies that can help solve the challenge within the transport sector. The Hydrogen Link Denmark Association and selected Danish players in the Hydrogen and Fuel Cell Partnership in Denmark has therefore prepared this analysis which describes a possible contribution to electrical transport, growth, CO{sub 2} reduction and fossil fuel independence by introduction of hydrogen for transport in Denmark up to 2050. The analysis is based on a possible share of hydrogen cars in the Danish car fleet in 2050 of 50% and the secondary effects of activation of the energy policy objectives for fossil fuel independence, and not least the significant potential for Danish exports of hydrogen and fuel cell technology and affected jobs. Similarly, the contribution of hydrogen for transport in relation to balancing the increased share of fluctuating renewable energy production was analyzed. (LN)

  12. Frame independent cosmological perturbations

    Energy Technology Data Exchange (ETDEWEB)

    Prokopec, Tomislav; Weenink, Jan, E-mail:, E-mail: [Institute for Theoretical Physics and Spinoza Institute, Utrecht University, Leuvenlaan 4, 3585 CE Utrecht (Netherlands)


    We compute the third order gauge invariant action for scalar-graviton interactions in the Jordan frame. We demonstrate that the gauge invariant action for scalar and tensor perturbations on one physical hypersurface only differs from that on another physical hypersurface via terms proportional to the equation of motion and boundary terms, such that the evolution of non-Gaussianity may be called unique. Moreover, we demonstrate that the gauge invariant curvature perturbation and graviton on uniform field hypersurfaces in the Jordan frame are equal to their counterparts in the Einstein frame. These frame independent perturbations are therefore particularly useful in relating results in different frames at the perturbative level. On the other hand, the field perturbation and graviton on uniform curvature hypersurfaces in the Jordan and Einstein frame are non-linearly related, as are their corresponding actions and n-point functions.

  13. Emissivity independent optical pyrometer (United States)

    Earl, Dennis Duncan; Kisner, Roger A.


    Disclosed herein are representative embodiments of methods, apparatus, and systems for determining the temperature of an object using an optical pyrometer. Certain embodiments of the disclosed technology allow for making optical temperature measurements that are independent of the surface emissivity of the object being sensed. In one of the exemplary embodiments disclosed herein, a plurality of spectral radiance measurements at a plurality of wavelengths is received from a surface of an object being measured. The plurality of the spectral radiance measurements is fit to a scaled version of a black body curve, the fitting comprising determining a temperature of the scaled version of the black body curve. The temperature is then output. The present disclosure is not to be construed as limiting and is instead directed toward all novel and nonobvious features and aspects of the various disclosed embodiments, alone or in various combinations and subcombinations with one another.

  14. Emissivity independent optical pyrometer

    Energy Technology Data Exchange (ETDEWEB)

    Earl, Dennis Duncan; Kisner, Roger A.


    Disclosed herein are representative embodiments of methods, apparatus, and systems for determining the temperature of an object using an optical pyrometer. Certain embodiments of the disclosed technology allow for making optical temperature measurements that are independent of the surface emissivity of the object being sensed. In one of the exemplary embodiments disclosed herein, a plurality of spectral radiance measurements at a plurality of wavelengths is received from a surface of an object being measured. The plurality of the spectral radiance measurements is fit to a scaled version of a black body curve, the fitting comprising determining a temperature of the scaled version of the black body curve. The temperature is then output. The present disclosure is not to be construed as limiting and is instead directed toward all novel and nonobvious features and aspects of the various disclosed embodiments, alone or in various combinations and subcombinations with one another.

  15. Gene expression profiling identifies activated growth factor signaling in poor prognosis (Luminal-B estrogen receptor positive breast cancer

    Directory of Open Access Journals (Sweden)

    Conus Nelly M


    Full Text Available Abstract Background Within estrogen receptor-positive breast cancer (ER+ BC, the expression levels of proliferation-related genes can define two clinically distinct molecular subtypes. When treated with adjuvant tamoxifen, those ER+ BCs that are lowly proliferative have a good prognosis (luminal-A subtype, however the clinical outcome of those that are highly proliferative is poor (luminal-B subtype. Methods To investigate the biological basis for these observations, gene set enrichment analysis (GSEA was performed using microarray data from 246 ER+ BC samples from women treated with adjuvant tamoxifen monotherapy. To create an in vitro model of growth factor (GF signaling activation, MCF-7 cells were treated with heregulin (HRG, an HER3 ligand. Results We found that a gene set linked to GF signaling was significantly enriched in the luminal-B tumors, despite only 10% of samples over-expressing HER2 by immunohistochemistry. To determine the biological significance of this observation, MCF-7 cells were treated with HRG. These cells displayed phosphorylation of HER2/3 and downstream ERK and S6. Treatment with HRG overcame tamoxifen-induced cell cycle arrest with higher S-phase fraction and increased anchorage independent colony formation. Gene expression profiles of MCF-7 cells treated with HRG confirmed enrichment of the GF signaling gene set and a similar proliferative signature observed in human ER+ BCs resistant to tamoxifen. Conclusion These data demonstrate that activation of GF signaling pathways, independent of HER2 over-expression, could be contributing to the poor prognosis of the luminal-B ER+ BC subtype.

  16. Increased expression of CYP4Z1 promotes tumor angiogenesis and growth in human breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Yu, Wei [Department of Pharmacology, School of Medicine, Wuhan University, Wuhan 430071 (China); Chai, Hongyan [Center for Gene Diagnosis, Zhongnan Hospital, Wuhan University, Wuhan 430071 (China); Li, Ying; Zhao, Haixia; Xie, Xianfei; Zheng, Hao; Wang, Chenlong; Wang, Xue [Department of Pharmacology, School of Medicine, Wuhan University, Wuhan 430071 (China); Yang, Guifang [Department of Pathology, Zhongnan Hospital, Wuhan University, Wuhan 430071 (China); Cai, Xiaojun [Department of Ophthalmology, Zhongnan Hospital, Wuhan University, Wuhan 430071 (China); Falck, John R. [Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390 (United States); Yang, Jing, E-mail: [Department of Pharmacology, School of Medicine, Wuhan University, Wuhan 430071 (China); Research Center of Food and Drug Evaluation, Wuhan University, Wuhan 430071 (China)


    Cytochrome P450 (CYP) 4Z1, a novel CYP4 family member, is over-expressed in human mammary carcinoma and associated with high-grade tumors and poor prognosis. However, the precise role of CYP4Z1 in tumor progression is unknown. Here, we demonstrate that CYP4Z1 overexpression promotes tumor angiogenesis and growth in breast cancer. Stable expression of CYP4Z1 in T47D and BT-474 human breast cancer cells significantly increased mRNA expression and production of vascular endothelial growth factor (VEGF)-A, and decreased mRNA levels and secretion of tissue inhibitor of metalloproteinase-2 (TIMP-2), without affecting cell proliferation and anchorage-independent cell growth in vitro. Notably, the conditioned medium from CYP4Z1-expressing cells enhanced proliferation, migration and tube formation of human umbilical vein endothelial cells, and promoted angiogenesis in the zebrafish embryo and chorioallantoic membrane of the chick embryo. In addition, there were lower levels of myristic acid and lauric acid, and higher contents of 20-hydroxyeicosatetraenoic acid (20-HETE) in CYP4Z1-expressing T47D cells compared with vector control. CYP4Z1 overexpression significantly increased tumor weight and microvessel density by 2.6-fold and 1.9-fold in human tumor xenograft models, respectively. Moreover, CYP4Z1 transfection increased the phosphorylation of ERK1/2 and PI3K/Akt, while PI3K or ERK inhibitors and siRNA silencing reversed CYP4Z1-mediated changes in VEGF-A and TIMP-2 expression. Conversely, HET0016, an inhibitor of the CYP4 family, potently inhibited the tumor-induced angiogenesis with associated changes in the intracellular levels of myristic acid, lauric acid and 20-HETE. Collectively, these data suggest that increased CYP4Z1 expression promotes tumor angiogenesis and growth in breast cancer partly via PI3K/Akt and ERK1/2 activation. -- Highlights: ► CYP4Z1 overexpression promotes human breast cancer growth and angiogenesis. ► The pro-angiogenic effects of CYP4Z1 have

  17. Clinical research of orthopedic treatment with implant anchorage in orthodontics%种植支抗在口腔正畸治疗中的临床研究

    Institute of Scientific and Technical Information of China (English)

    李茜; 王军


    目的:分析研究种植支抗在口腔正畸治疗中的临床应用情况.方法:回顾性分析2009年1月-2010年1月期间在我院治疗的34例需种植义齿修复同时件错合畸形的患者;或者常规支抗缺乏或不理想的错合畸形的成年患者的临床资料.结果:应用Branemark种植体在牙列缺损律错合畸形患者的缺失牙医植入,以此为种植支抗对34例错合畸形患者进行了治疗.34例患者全部顺利完成治疗,而且种植体无明显松动,34例患者经畸形矫正和义齿修复后获得满意效果.结论:种植支抗能够应用于需种植义齿修复同时件错合畸形的患者,且对口颌系统无不良作用,有较好的临床效果.%Objective: To the clinical research of orthopedic treatment with implant anchorage in orthodontics. Methods: A retrospective analysis a-bout clinical data treatment with 34 patients who required implant restoration at the same time pieces of malocclusion patients and lack of conventional anchorage or unsatisfactory malocclusion in January from 2009 to2010 in our hospital. Results! Application of Branemark implants in the dentition defect with malocclusion in patients who missing teeth implants, the 34 patients with malocclusion were treated on this implant. The whole patients completed treatment successfully without implant loosening. Have obtained satisfactory results. Conclusion: implant anchorage can be used to plant the same time pieces of malocclusion patients,and the corresponding jaw system without adverse effects, have better clinical results.

  18. DeltaNp63alpha-mediated induction of epidermal growth factor receptor promotes pancreatic cancer cell growth and chemoresistance.

    Directory of Open Access Journals (Sweden)

    Alexey V Danilov

    Full Text Available Pancreatic ductal adenocarcinoma (PDAC is highly resistant to current chemotherapy regimens, in part due to alterations in the p53 tumor suppressor pathway. p53 homolog p63 is a transcription factor essential for the development and differentiation of epithelial surfaces. However its function in cancer is controversial and its role in PDAC is not known. We discovered that ΔNp63α was the predominantly expressed p63 variant in pancreatic cancer cell lines. ΔNp63α protein and mRNA levels were high in T3M4, BxPC3 and COLO-357 pancreatic cancer cells and low in ASPC-1 and PANC-1 cells. Overexpression of ΔNp63α in PANC-1 cells and shRNA-mediated knockdown in T3M4 cells indicated that ΔNp63α promoted anchorage-dependent and -independent growth, motility and invasion, and enhanced resistance to cisplatin-induced apoptosis. Epidermal growth factor receptor (EGFR signaling pathways contribute to the biological aggressiveness of PDAC, and we found that the motogenic effects of ΔNp63α were augmented in presence of EGF. Ectopic expression of ΔNp63α resulted in upregulation of EGFR and β1-integrin in PANC-1 cells. Conversely, ΔNp63α knockdown had an opposite effect in T3M4 cells. ΔNp63α potentiated EGF-mediated activation of ERK, Akt and JNK signaling. Chromatin immunoprecipitation and functional reporter assays demonstrated that ΔNp63α activated EGFR transcription. 14-3-3σ transcription was also positively regulated by ΔNp63α and we have previously shown that 14-3-3σ contributes to chemoresistance in pancreatic cancer cell lines. Conversely, shRNA-mediated knockdown of 14-3-3σ led to abrogation of the ΔNp63α effects on cell proliferation and invasion. Thus, p53 homolog ΔNp63α enhances the oncogenic potential of pancreatic cancer cells through trans-activation of EGFR and 14-3-3σ.

  19. 铁路悬索桥大吨位隧道锚承载性能分析%Analysis on Bearing Performance of Large-tonnage Tunnel-type Anchorage of Railway Suspension Bridge

    Institute of Scientific and Technical Information of China (English)

    江南; 冯君


    丽香铁路金沙江大桥是我国首座采用大吨位隧道式锚碇的铁路悬索桥.本文采用三维弹塑性有限元方法对隧道锚的变形机理、承载能力以及围岩稳定状态进行分析.研究结果表明:在正常缆力作用下,锚碇体及周围岩体的位移均处于毫米量级,远小于悬索桥塔顶允许位移;锚碇体整体表现为以前底板为支点,锚碇体后部向上转动和整体向前滑移的变形模式;锚碇体及围岩绝大部分处于三向受压状态,只是在锚碇底端与下部围岩的接触部分,以及顶拱与边墙交界处局部范围内存在拉应力,建议在这些部位采取措施重点加强;基于超载极限分析法计算得到锚碇体的整体抗滑安全系数在9以上.有限元分析结果为铁路悬索桥隧道锚的优化设计提供了理论依据.%The Jinsha River Bridge of the Lijiang-Xianggelila Railway is the first railway suspension bridge with tunnel type anchorages of large tonnage in China.By using the three dimensional elastoplastic finite element method,the deformation mechanism & bearing capacity of the tunnel anchorage and the stability of surrounding rock were analyzed.The results show as follows:Under the action of normal cable forces,the displacements of the anchorage body and surrounding rock are in the millimeter range,which are far less than the allowable displacements of the suspension bridge tower;the deformation mode of the anchorage body includes the back part of the anchorage body turning upward with the front bottom plate as the fulcrum and the whole anchorage body sliding forward; most parts of the anchorage body and surrounding rock are in the triaxial compression state,except that the contact surface between the bottom end of the anchorage body and the under surrounding rock and,the local boundary area between the crown hog and flank wall are subjected to tensile stresses where stressed strengthening is needed;with the overload limit analysis method

  20. PPARγ-Independent Mechanism

    Directory of Open Access Journals (Sweden)

    Christopher M. Hogan


    Full Text Available Acute and chronic lung inflammation is associated with numerous important disease pathologies including asthma, chronic obstructive pulmonary disease and silicosis. Lung fibroblasts are a novel and important target of anti-inflammatory therapy, as they orchestrate, respond to, and amplify inflammatory cascades and are the key cell in the pathogenesis of lung fibrosis. Peroxisome proliferator-activated receptor gamma (PPARγ ligands are small molecules that induce anti-inflammatory responses in a variety of tissues. Here, we report for the first time that PPARγ ligands have potent anti-inflammatory effects on human lung fibroblasts. 2-cyano-3, 12-dioxoolean-1, 9-dien-28-oic acid (CDDO and 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2 inhibit production of the inflammatory mediators interleukin-6 (IL-6, monocyte chemoattractant protein-1 (MCP-1, COX-2, and prostaglandin (PGE2 in primary human lung fibroblasts stimulated with either IL-1β or silica. The anti-inflammatory properties of these molecules are not blocked by the PPARγ antagonist GW9662 and thus are largely PPARγ independent. However, they are dependent on the presence of an electrophilic carbon. CDDO and 15d-PGJ2, but not rosiglitazone, inhibited NF-κB activity. These results demonstrate that CDDO and 15d-PGJ2 are potent attenuators of proinflammatory responses in lung fibroblasts and suggest that these molecules should be explored as the basis for novel, targeted anti-inflammatory therapies in the lung and other organs.

  1. Opposing activities of the Ras and Hippo pathways converge on regulation of YAP protein turnover

    DEFF Research Database (Denmark)

    Hong, Xin; Nguyen, Thanh Hung; Chen, Qingfeng;


    Cancer genomes accumulate numerous genetic and epigenetic modifications. Yet, human cellular transformation can be accomplished by a few genetically defined elements. These elements activate key pathways required to support replicative immortality and anchorage independent growth, a predictor of ...

  2. Depletion of OLFM4 gene inhibits cell growth and increases sensitization to hydrogen peroxide and tumor necrosis factor-alpha induced-apoptosis in gastric cancer cells

    Directory of Open Access Journals (Sweden)

    Liu Rui-hua


    Full Text Available Abstract Background Human olfactomedin 4 (OLFM4 gene is a secreted glycoprotein more commonly known as the anti-apoptotic molecule GW112. OLFM4 is found to be frequently up-regulated in many types of human tumors including gastric cancer and it was believed to play significant role in the progression of gastric cancer. Although the function of OLFM4 has been indicated in many studies, recent evidence strongly suggests a cell or tissue type-dependent role of OLFM4 in cell growth and apoptosis. The aim of this study is to examine the role of gastric cancer-specific expression of OLFM4 in cell growth and apoptosis resistance. Methods OLFM4 expression was eliminated by RNA interference in SGC-7901 and MKN45 cells. Cell proliferation, anchorage-independent growth, cell cycle and apoptosis were characterized in vitro. Tumorigenicity was analyzed in vivo. The apoptosis and caspase-3 activation in response to hydrogen peroxide (H2O2 or tumor necrosis factor-alpha (TNF α were assessed in the presence or absence of caspase inhibitor Z-VAD-fmk. Results The elimination of OLFM4 protein by RNA interference in SGC-7901 and MKN45 cells significantly inhibits tumorigenicity both in vitro and in vivo by induction of cell G1 arrest (all P 2O2 or TNF α-induced apoptosis and caspase-3 activity (all P 2O2 or TNF α-induced apoptosis in OLFM4 knockdown cells (all P Conclusion Our study suggests that depletion of OLFM4 significantly inhibits tumorigenicity of the gastric cancer SGC-7901 and MKN45 cells. Blocking OLFM4 expression can sensitize gastric cancer cells to H2O2 or TNF α treatment by increasing caspase-3 dependent apoptosis. A combination strategy based on OLFM4 inhibition and anticancer drugs treatment may provide therapeutic potential in gastric cancer intervention.

  3. H-ras-transformed NRK-52E renal epithelial cells have altered growth, morphology, and cytoskeletal structure that correlates with renal cell carcinoma in vivo. (United States)

    Best, C J; Tanzer, L R; Phelps, P C; Merriman, R L; Boder, G G; Trump, B F; Elliget, K A


    We studied the effect of the ras oncogene on the growth kinetics, morphology, cytoskeletal structure, and tumorigenicity of the widely used NRK-52E rat kidney epithelial cell line and two H-ras oncogene-transformed cell lines, H/1.2-NRK-52E (H/1.2) and H/6.1-NRK-52E (H/6.1). Population doubling times of NRK-52E, H/1.2, and H/6.1 cells were 28, 26, and 24 h, respectively, with the transformed cells reaching higher saturation densities than the parent cells. NRK-52E cells had typical epithelial morphology with growth in colonies. H/1.2 and H/6.1 cell colonies were more closely packed, highly condensed, and had increased plasma membrane ruffling compared to parent cell colonies. NRK-52E cells showed microfilament, microtubule, and intermediate filament networks typical of epithelial cells, while H/1.2 and H/6.1 cells showed altered cytoskeleton architecture, with decreased stress fibers and increased microtubule and intermediate filament staining at the microtubule organizing center. H/1.2 and H/6.1 cells proliferated in an in vitro soft agar transformation assay, indicating anchorage-independence, and rapidly formed tumors in vivo with characteristics of renal cell carcinoma, including mixed populations of sarcomatoid, granular, and clear cells. H/6.1 cells consistently showed more extensive alterations of growth kinetics, morphology, and cytoskeleton than H/1.2 cells, and formed tumors of a more aggressive phenotype. These data suggest that analysis of renal cell characteristics in vitro may have potential in predicting tumor behavior in vivo, and significantly contribute to the utility of these cell lines as in vitro models for examining renal epithelial cell biology and the role of the ras proto-oncogene in signal transduction involving the cytoskeleton.

  4. 深基坑锚固工程中成孔技术%Bore-making Technique in the Anchorage Project of Deep Foundation Pit

    Institute of Scientific and Technical Information of China (English)



    Impact Spiral Drilling is a new bore-making techni que. Its usage in the anchorage project of deep foundation ditch can solve the p roblem of drilling in the soft and hard cross stratum. In this article, the auth or specially introduces the structure of impact spiral drill machine and its ope ration techniques.%冲击螺旋钻孔是一种新的成孔工艺,在深基坑的锚固技术中成功地解决了软硬互层、夹杂地层的钻进。本文详细介绍了冲击螺旋钻的构造和成孔操作技术。

  5. Conditions of Proper Interaction of Low-Pressure Injection Piles (LIP) with Structure and Soil, Carrying Capacity of Pile Anchorage in Foundation (United States)

    Pachla, Henryk


    The formation of a pile in the existing foundation and soil creates a new foundation construction which has a structure of foundation-pile-soil. This construction must be able to transfer loads from the foundation to the pile and from the pile to the soil. The pile structure has to transfer an imposed load. From the point of view of continuum mechanics determination of the capacity of such a system is preceded by the analysis of contact problem of three contact surfaces. Each of these surfaces is determined by different pairs of materials. The pair which creates a pile anchorage is a material from which the foundation is built (structure of stone and grout, brick and grout, concrete or reinforced concrete and grout. The pile structure is formed by grout and steel rebar. The pile formed in soil is created by a pair of grout and soil. What is important is that on contact surfaces the materials adhering to one another are subjected to different deformation types that are controlled by mechanical properties and geometry of these surfaces. In the paper, additional conditions that should be fulfilled for the foundation-pile-soil system to make load transfer from foundation to soil possible and safe are presented. The results of research done by the author on foundation-pile contact surface are discussed. The tests were targeted at verifying the bearing capacity of anchorage and deformation of piles made of grout and other materials from which foundations are built. The specimens were tested in tension and compression. The experiments were conducted on the amount specimens which is regarded as small sample to enable the statistical analysis of the results.

  6. Media independence and dividend policy

    DEFF Research Database (Denmark)

    Farooq, Omar; Dandoune, Salma


    independence and dividend policies in emerging markets. Using a dataset from twenty three emerging markets, we show a significantly negative relationship between dividend policies (payout ratio and decision to pay dividend) and media independence. We argue that independent media reduces information asymmetries...... for stock market participants. Consequently, stock market participants in emerging markets with more independent media do not demand as high and as much dividends as their counterparts in emerging markets with less independent media. We also show that press independence is more important in defining......Can media pressurize managers to disgorge excess cash to shareholders? Do firms in countries with more independent media follow different dividend policies than firms with less independent media? This paper seeks to answer these questions and aims to document the relationship between media...

  7. Media independence and dividend policy

    DEFF Research Database (Denmark)

    Farooq, Omar; Dandoune, Salma


    for stock market participants. Consequently, stock market participants in emerging markets with more independent media do not demand as high and as much dividends as their counterparts in emerging markets with less independent media. We also show that press independence is more important in defining...... independence and dividend policies in emerging markets. Using a dataset from twenty three emerging markets, we show a significantly negative relationship between dividend policies (payout ratio and decision to pay dividend) and media independence. We argue that independent media reduces information asymmetries......Can media pressurize managers to disgorge excess cash to shareholders? Do firms in countries with more independent media follow different dividend policies than firms with less independent media? This paper seeks to answer these questions and aims to document the relationship between media...

  8. Independent sets in chain cacti


    Sedlar, Jelena


    In this paper chain cacti are considered. First, for two specific classes of chain cacti (orto-chains and meta-chains of cycles with h vertices) the recurrence relation for independence polynomial is derived. That recurrence relation is then used in deriving explicit expressions for independence number and number of maximum independent sets for such chains. Also, the recurrence relation for total number of independent sets for such graphs is derived. Finaly, the proof is provided that orto-ch...

  9. Studying the Independent School Library (United States)

    Cahoy, Ellysa Stern; Williamson, Susan G.


    In 2005, the American Association of School Librarians' Independent Schools Section conducted a national survey of independent school libraries. This article analyzes the results of the survey, reporting specialized data and information regarding independent school library budgets, collections, services, facilities, and staffing. Additionally, the…

  10. Independent sets in chain cacti

    CERN Document Server

    Sedlar, Jelena


    In this paper chain cacti are considered. First, for two specific classes of chain cacti (orto-chains and meta-chains of cycles with h vertices) the recurrence relation for independence polynomial is derived. That recurrence relation is then used in deriving explicit expressions for independence number and number of maximum independent sets for such chains. Also, the recurrence relation for total number of independent sets for such graphs is derived. Finaly, the proof is provided that orto-chains and meta-chains are the only extremal chain cacti with respect to total number of independent sets (orto-chains minimal and meta-chains maximal).

  11. Safety evaluation system for anchored vessels in Tianjin anchorage under strong wind%天津港锚地大风条件下锚泊船安全评估系统

    Institute of Scientific and Technical Information of China (English)

    吴金龙; 吴彬贵; 刘大刚; 张斌; 罗红红


    To guarantee the safety of anchored vessels under strong wind, the safe lengths of let-going chain and the safe distance between vessels are calculated, and the warning grades of anchored vessels under strong wind in Tianjin anchorage is made according to the actual condition of Tianjin anchorage. A useful safety evaluation model for anchored vessels under strong wind in Tianjin anchorage is built. On that basis, the software of safety evaluation system for anchored vessels under strong wind in Tianjin anchorage is developed, which can provide the warning grades under the coming strong wind for each anchorage area in Tianjin anchorage dynamically and visually in advance of hours according to the wind speed forecast from meteorological department. It will be helpful to confirm the safety condition of anchored vessels for marine administration before strong wind coming, and reduce the accidents of dragging and collision, which can guarantee the safety production and enhance economic efficiency for shipping companies.%为保障大风期间船舶的锚泊安全,根据天津港锚地的具体情况,计算大风条件下天津港各锚地的安全出链长度和船舶之间的安全距离,制定天津港锚地大风条件下的锚泊船预警标准,建立可用于上述条件下的锚泊船实用安全评估模型.在此基础上,研制天津港锚地大风条件下的锚泊船安全评估系统软件.该软件可根据气象部门提供的大风风速预报,提前若干小时动态直观地给出天津港各锚地在未来大风条件下的预警等级,使得海事管理部门在大风来临前能够对锚泊船的锚泊状态进行安全确认,以减少大风来临时走锚和碰撞事故的发生,达到保障船运企业安全生产、提高经济效率的目的.

  12. Targeting non-small cell lung cancer cells by dual inhibition of the insulin receptor and the insulin-like growth factor-1 receptor.

    Directory of Open Access Journals (Sweden)

    Emma E Vincent

    Full Text Available Phase III trials of the anti-insulin-like growth factor-1 receptor (IGF1R antibody figitumumab in non-small cell lung cancer (NSCLC patients have been discontinued owing to lack of survival benefit. We investigated whether inhibition of the highly homologous insulin receptor (IR in addition to the IGF1R would be more effective than inhibition of the IGF1R alone at preventing the proliferation of NSCLC cells. Signalling through IGF1R and IR in the NSCLC cell lines A549 and Hcc193 was stimulated by a combination of IGF1, IGF2 and insulin. It was inhibited by antibodies that block ligand binding, αIR3 (IGF1R and IR47-9 (IR, and by the ATP-competitive small molecule tyrosine kinase inhibitors AZ12253801 and NVPAWD742 which inhibit both IGF1R and IR tyrosine kinases. The effect of inhibitors was determined by an anchorage-independent proliferation assay and by analysis of Akt phosphorylation. In Hcc193 cells the reduction in cell proliferation and Akt phosphorylation due to anti-IGF1R antibody was enhanced by antibody-mediated inhibition of the IR whereas in A549 cells, with a relatively low IR:IGF1R expression ratio, it was not. In each cell line proliferation and Akt phosphorylation were more effectively inhibited by AZ12253801 and NVPAWD742 than by combined αIR3 and IR47-9. When the IGF1R alone is inhibited, unencumbered signalling through the IR can contribute to continued NSCLC cell proliferation. We conclude that small molecule inhibitors targeting both the IR and IGF1R more effectively reduce NSCLC cell proliferation in a manner independent of the IR:IGF1R expression ratio, providing a therapeutic rationale for the treatment of this disease.

  13. The Independence of Jane Eyre

    Institute of Scientific and Technical Information of China (English)



    <正>Ⅰ.General Review of Jane Eyre’s Independence Jane’s independence also has something to do with dignity.Every time she was teased by her cousin,she would resist rather than keep silent.Even when she stayed with the so-called upperclass people,she behaved without any self-humiliation.Jane’s sufferings that give rise to her independence and unconquerable spirit to stay with Rochester,Jane didn’t feel herself inferior

  14. Nuclear, uranium, reserves, sustainability, independence; Nucleaire, Uranium, reserves, durabilite, independance

    Energy Technology Data Exchange (ETDEWEB)

    Acket, C


    In order to evaluate the energy independence concerning the nuclear energy, the author takes the state of the art about the uranium. He details the fuel needs, the reserves on the base of the today available techniques, the reserves on the base of the future techniques and concludes positively on the energy independence for the nuclear. (A.L.B.)

  15. Substrate-Independent Growth of Atomically Precise Chiral Graphene Nanoribbons (United States)


    Contributing to the need for new graphene nanoribbon (GNR) structures that can be synthesized with atomic precision, we have designed a reactant that renders chiral (3,1)-GNRs after a multistep reaction including Ullmann coupling and cyclodehydrogenation. The nanoribbon synthesis has been successfully proven on different coinage metals, and the formation process, together with the fingerprints associated with each reaction step, has been studied by combining scanning tunneling microscopy, core-level spectroscopy, and density functional calculations. In addition to the GNR’s chiral edge structure, the substantial GNR lengths achieved and the low processing temperature required to complete the reaction grant this reactant extremely interesting properties for potential applications. PMID:27548516

  16. Movimentação de molares inferiores ancorados em mini-parafusos Mandibular molar uprighting, using mini-screw as anchorage

    Directory of Open Access Journals (Sweden)

    Rosana Canteras Di Matteo


    Full Text Available Freqüentemente a movimentação ortodôntica exige recursos adicionais de ancoragem. Os mini-parafusos têm-se apresentado como uma possível solução. O propósito deste trabalho foi estabelecer um método para a verticalização de molares inferiores inclinados para mesial, utilizando ancoragem em mini-parafusos colocados na região de linha oblíqüa externa da mandíbula. Foram selecionados três pacientes entre 40 a 48 anos (dois do gênero feminino, um do gênero masculino, com molares inferiores inclinados para mesial e distalmente posicionados às áreas edêntulas. Os pacientes foram tratados ortodonticamente durante um período de 6 a 12 meses, com técnica ortodôntica MD3. Mini-parafusos de titânio foram colocados bilateralmente com anestesia local. Uma incisão sobre a linha oblíqüa externa da mandíbula, medindo aproximadamente 1 cm foi realizada em cada lado, distalmente aos molares inclinados. Após descolamento muco-periosteal, mini-parafusos foram implantados e foram realizadas suturas deixando suas cabeças exteriorizadas. Uma semana após a remoção das suturas, cargas ortodônticas (entre 150 a 200 gramas/força foram aplicadas através de forças elásticas. Verificamos que alguma inflamação foi observada ao redor dos mini-parafusos, mas foi controlada com procedimentos de higienização. O procedimento cirúrgico é simples, podendo ser realizado pelo ortodontista; as formas dimensionais dos mini-parafusos são adequadas e estes são de fácil remoção após uso. Concluímos que o uso de mini-parafusos representa uma alternativa efetiva de ancoragem ortodôntica na verticalização de molares inferiores.Tooth movement frequently requires additional anchorage resources. Mini-screws have been used as a possible solution to this matter. The purpose of this study was to establish a method of mandibular molar uprighting, using mini-screw as anchorage, positioned on the mandibular external oblique line, behind and

  17. The novel ATP-competitive inhibitor of the MET hepatocyte growth factor receptor EMD1214063 displays inhibitory activity against selected MET-mutated variants. (United States)

    Medová, Michaela; Pochon, Benoît; Streit, Bruno; Blank-Liss, Wieslawa; Francica, Paola; Stroka, Deborah; Keogh, Adrian; Aebersold, Daniel M; Blaukat, Andree; Bladt, Friedhelm; Zimmer, Yitzhak


    The receptor tyrosine kinase MET is a prime target in clinical oncology due to its aberrant activation and involvement in the pathogenesis of a broad spectrum of malignancies. Similar to other targeted kinases, primary and secondary mutations seem to represent an important resistance mechanism to MET inhibitors. Here, we report the biologic activity of a novel MET inhibitor, EMD1214063, on cells that ectopically express the mutated MET variants M1268T, Y1248H, H1112Y, L1213V, H1112L, V1110I, V1206L, and V1238I. Our results show a dose-dependent decrease in MET autophosphorylation in response to EMD1214063 in five of the eight cell lines (IC50 2-43 nmol/L). Blockade of MET by EMD1214063 was accompanied by a reduced activation of downstream effectors in cells expressing EMD1214063-sensitive mutants. In all sensitive mutant-expressing lines, EMD1214063 altered cell-cycle distribution, primarily with an increase in G1 phase. EMD1214063 strongly influenced MET-driven biologic functions, such as cellular morphology, MET-dependent cell motility, and anchorage-independent growth. To assess the in vivo efficacy of EMD1214063, we used a xenograft tumor model in immunocompromised mice bearing NIH3T3 cells expressing sensitive and resistant MET-mutated variants. Animals were randomized for the treatment with EMD1214063 (50 mg/kg/d) or vehicle only. Remarkably, five days of EMD1214063 treatment resulted in a complete regression of the sensitive H1112L-derived tumors, whereas tumor growth remained unaffected in mice with L1213V tumors and in vehicle-treated animals. Collectively, the current data identifies EMD1214063 as a potent MET small-molecule inhibitor with selective activity towards mutated MET variants. ©2013 AACR.

  18. 基于Mindlin解的压力型锚杆锚固段的受力分析%Mechanical analysis of anchorage segment of pressure-type cable based on the Mindlin solution

    Institute of Scientific and Technical Information of China (English)

    贺建清; 胡成兵; 张建超


    假设锚杆为与周围介质相同的材料,视锚杆作用的岩土体为弹性半空间位移体;基于Mindlin位移解,求出集中力作用下周围岩土体沿锚固体的轴向位移;根据压力型锚杆锚固段的受力状态,计算锚固体在轴向荷载作用下压缩变形,利用锚固体与周围岩土体变形协调假定,推导出锚固段轴向应力和剪应力分布的理论解.经过与已有现场试验实测数据对比分析,验证了理论解的可行性,并在此基础上讨论了相关岩土参数对锚固段轴向应力和剪应力的影响.锚杆现场试验和理论分析结果表明:压力型锚杆的锚固段所受轴向应力和剪应力与锚固力成正比;压力型锚杆的锚固段所受剪应力的分布形式受周围岩土体弹模、泊松比以及锚固体与周围岩土体界面的内摩擦角等因素的影响.其中周围岩土体的弹模影响最大.%Assuming that cable has the same material properties with the surrounding rock soil and there is a displacement in an elastic half-space occurred for the rock and soil mass reinforced with cable, axial displacement of surrounding rock soil mass along cable under anchorage force was calculated based on Mindlin displacement solution. Based on the stress state of anchorage segment of pressure-type cable, the compression deformation of anchorage body under axial load was also obtained. Theoretical solutions for the distribution of axial stress and shear stress on anchorage segment of pressure-type cable were derived on the assumption of a compatible deformation between anchorage body and surrounding rock soil mass. After comparing with the existed data of in-situ test, theoretical solutions proved to be feasible. On this basis, the influence of related mechanical parameters of rock and soil on shear stress and axial stress were discussed. Experimental and theoretical analysis results indicated that the axial normal stress and shear stress on anchorage segment of

  19. Mesialização de molares com ancoragem em mini-implantes Mesial movement of molars with mini-implants anchorage

    Directory of Open Access Journals (Sweden)

    Marcos Janson


    Full Text Available INTRODUÇÃO: é muito comum, na rotina do consultório odontológico, especialmente em Ortodontia, o paciente, após avaliar o plano de tratamento proposto, questionar sobre a possibilidade de fechamento de espaços presentes, ocasionados pela perda de dentes permanentes. O ortodontista, frente a essa questão, tem que avaliar diversos fatores, tais como a má oclusão presente, a integridade do osso e das raízes, o tempo de tratamento e a geometria do posicionamento dentário, que é o que permite avaliar se, com o fechamento dos espaços e, conseqüentemente, a perda de ancoragem dos segmentos anteriores, a finalização estará de acordo com os ideais que regem a especialidade. Com o advento dos mini-implantes, as possibilidades desta abordagem terapêutica aumentaram, pois o efeito adverso da perda de ancoragem pode ser eliminado e, com isso, o paciente pode ser beneficiado. No entanto, os outros fatores envolvidos, assim como a mecânica do movimento, requerem especial atenção. OBJETIVOS: no presente artigo serão abordados os fatores envolvidos neste tipo de tratamento, o raciocínio na tomada de decisões e os detalhes importantes que devem ser observados durante a condução da mecânica, ilustrados com casos clínicos.INTRODUCTION: It's routine, especially at the orthodontic office, the patient, after the assessment of the proposed treatment plan, answer about the possibility of closing their edentulous spaces caused by missed permanent teeth. In these situations, several factors must be evaluated, like the present malocclusion, the bone and roots integrity, the treatment time and the geometry of teeth positioning, that is what permits to assess if the loss of anchorage from the anterior segments, during the space closure, would permit the occlusion to end within the orthodontic ideals. With the mini-implants, the possibilities of this therapeutic approach have been improved, since the adverse effects are eliminated with the

  20. Marketing Handbook for Independent Schools. (United States)

    Boarding Schools, Boston, MA.

    This publication is a resource to help independent schools attract more familites to their institutions and to increase the voluntary support by the larger community surrounding the school. The first chapter attempts to dispel misconceptions, define pertinent marketing terms, and relate their importance to independent schools. The rest of the book…

  1. Central bank independence and ageing


    Farvaque, Etienne; Héricourt, Jérôme; Lagadec, Gaël


    We contrast the influence of demography and central bank independence on inflation. The recent demographic trends in developed countries are shown to weight more on inflation than central bank independence, while the contrary stands for the period from 1960 to 1979.

  2. Inhibition of PRL-2·CNNM3 Protein Complex Formation Decreases Breast Cancer Proliferation and Tumor Growth. (United States)

    Kostantin, Elie; Hardy, Serge; Valinsky, William C; Kompatscher, Andreas; de Baaij, Jeroen H F; Zolotarov, Yevgen; Landry, Melissa; Uetani, Noriko; Martínez-Cruz, Luis Alfonso; Hoenderop, Joost G J; Shrier, Alvin; Tremblay, Michel L


    The oncogenic phosphatase of regenerating liver 2 (PRL-2) has been shown to regulate intracellular magnesium levels by forming a complex through an extended amino acid loop present in the Bateman module of the CNNM3 magnesium transporter. Here we identified highly conserved residues located on this amino acid loop critical for the binding with PRL-2. A single point mutation (D426A) of one of those critical amino acids was found to completely disrupt PRL-2·human Cyclin M 3 (CNNM3) complex formation. Whole-cell voltage clamping revealed that expression of CNNM3 influenced the surface current, whereas overexpression of the binding mutant had no effect, indicating that the binding of PRL-2 to CNNM3 is important for the activity of the complex. Interestingly, overexpression of the CNNM3 D426A-binding mutant in cancer cells decreased their ability to proliferate under magnesium-deprived situations and under anchorage-independent growth conditions, demonstrating a PRL-2·CNNM3 complex-dependent oncogenic advantage in a more stringent environment. We further confirmed the importance of this complex in vivo using an orthotopic xenograft breast cancer model. Finally, because molecular modeling showed that the Asp-426 side chain in CNNM3 buries into the catalytic cavity of PRL-2, we showed that a PRL inhibitor could abrogate complex formation, resulting in a decrease in proliferation of human breast cancer cells. In summary, we provide evidence that this fundamental regulatory aspect of PRL-2 in cancer cells could potentially lead to broadly applicable and innovative therapeutic avenues.

  3. 提高车辆安全带锚固点强度的方法研究%Study on improving the strength of the seat-belts anchorages

    Institute of Scientific and Technical Information of China (English)



    按照国家标准要求,对某型汽车座椅安全带进行强度试验,发现后排座椅安全带锚点处的后地板破裂.针对该问题,在ANSYS软件中建立了座椅安全带的有限元模型,通过有限元分析结果与试验结果的对比,证明有限元模型的可靠性.利用非线性有限元法对安全带锚固点的强度进行了研究,提出了一些可以提高安全带锚固点强度的方法.%According to the national standards requiements , the strength test was done to the seat-belts of a certain type of cars. The results show that the strength of rear seat-belt anchorages cound not meet the national standards. According to the national standards, a finite element model of the seat-belts was built using ANSYS software. The results of the finite element simulation analysis were compared with the experimental results, which proved the reliability of finite element model. The strength of belts anchorages was studied using nonlinear finite element method, and some methods were put forward in order to improve the strength of seat-belt anchorages.

  4. 国内大跨径悬索桥锚碇锚固系统比较研究%The Compare and Investigation of Anchor System for Anchorage of Domestic Long-Span Suspension Bridge

    Institute of Scientific and Technical Information of China (English)

    李海; 鲜亮; 姚志安


    The anchor system for anchorage of suspension bridge plays an important controlling role in overall safety of structure . The paper mainly compares the different anchor system for anchorage of domestic long-span suspension bridge, and Makes an investigation on durability 、reliability and economy, which can be used for reference on adoption for future anchor system for anchorage of long-span suspension bridge.%悬索桥锚碇锚固系统在保证结构整体安全上具有重要控制作用.主要对我国目前大跨径悬索桥锚固系统不同体系作了比较,并对各种体系的耐久性、可靠性及经济性等方面进行了研究,为今后大跨径悬索桥锚固系统体系的采用提供了借鉴.

  5. 微种植体支抗在安氏Ⅱ类1分类错牙合中的应用%The Application of Micro-implants Anchorage in Angle Class Ⅱ Division 1 Malocclusion

    Institute of Scientific and Technical Information of China (English)



    Angle class Ⅱ division 1 malocclusion prevalence is high. The premise of such disease to be successfully treated is the perfect anchorage control. Mini-implants anchorage provides stable anchorage effects for the orthodontic treatment, which is recognized and accepted by the majority of physicians. In practical application process, how to optimize the use of micro-implants to treatment of Angle class Ⅱ division 1 malocclusion is one of the difficulties in orthodontic.%安氏Ⅱ类1分类错牙合畸形患病率较高,正确的支抗设计和良好的支抗控制是这类错牙合获得成功矫治的前提.近年来,微种植体支抗由于为正畸治疗中提供稳定支抗效果而逐渐被广大医师认识和接受.在实际应用过程中,如何优化使用微种植体治疗安氏Ⅱ类1分类错牙合是当今正畸治疗的难点之一.

  6. The effect of canine disimpaction performed with temporary anchorage devices (TADs before comprehensive orthodontic treatment to avoid root resorption of adjacent teeth

    Directory of Open Access Journals (Sweden)

    Farzin Heravi


    Full Text Available ABSTRACT Objective: The aim of this study was to evaluate the movement of impacted canines away from the roots of neighboring teeth before full-mouth bracket placement, performed by means of TADs to decrease undesired side effects on adjacent teeth. Methods: The study sample consisted of 34 palatally impacted canines, being 19 in the experimental group and 15 in the control group. In the experimental group, before placement of brackets, the impacted canine was erupted by means of miniscrews. In the control group, after initiation of comprehensive orthodontics, canine disimpaction was performed by means of a cantilever spring soldered to a palatal bar. At the end of treatment, volume of lateral incisors and canine root resorption were measured and compared by means of a CBCT-derived tridimensional model. Visual Analogue Scale (VAS score, bleeding on probing (BOP and gingival index (GI were recorded. Clinical success rate was also calculated. Results: The volume of root resorption of lateral teeth in the control group was significantly greater than in the experimental group (p < 0.001. At the end of treatment, VAS score, GI and BOP were not significantly different between the two groups. Conclusion: Based on our results, it seems that disimpaction of canines and moving them to the arch can be done successfully carried out with minimal side effects by means of skeletal anchorage.

  7. Apical root resorption in maxillary incisors when employing micro-implant and J-hook headgear anchorage: a 4-month radiographic study. (United States)

    Wang, Qingzhu; Chen, Wenjing; Smales, Roger J; Peng, Hui; Hu, Xiaokun; Yin, Lu


    This study evaluated, over a 4-month study period, the amount of apical root resorption occurring in maxillary central incisors following their retraction when employing either micro-implant or J-hook headgear anchorage. The prospective randomised clinical trial was conducted in Orthodontic Clinic, College of Stomatology, China from 2008-2009. Subjects are patients requiring fixed appliances on waiting list (n=20). In female Han Chinese patients aged from 16-26 years, standardized periapical radiographs from 10 randomly assigned patients with maxillary protrusions comprising the micro-implant group, and from 10 similar patients comprising the J-hook headgear group, were assessed for maxillary central incisor apical root resorption. Measurements before and after orthodontic therapy were also obtained from lateral cephalometric radiographs to calculate incisor horizontal retraction and vertical intrusion distances. Estimated retraction force vectors were calculated in horizontal and vertical directions for both treatment groups. Data analysis employed t-tests and the Pearson correlation test, with α=0.05 for statistical significance. The results showed that when compared with the J-hook group, significantly more apical root resorption shortening of the maxillary central incisors was observed in the micro-implant group (1.27 mm difference, 95% CI=0.70-1.84, Presorption shortening and maxillary central incisor retraction than when intermittent J-hook retraction was employed. The employment of continuous duration orthodontic forces presents a risk for increased apical root resorption that requires careful radiographic monitoring.

  8. Approximation and contact of the maxillary central incisor roots with the incisive canal after maximum retraction with temporary anchorage devices: Report of 2 patients. (United States)

    Chung, Chooryung J; Choi, Yoon Jeong; Kim, Kyung-Ho


    The incisive canal is located on the median plane of the maxilla, posterior to the roots of the central incisor. Although the incisive canal is not considered an anatomic structure that may limit tooth movement, it has recently gained attention regarding the possibilities of surgical invasion and associated complications because of its proximity to the maxillary central incisors. In the 2 illustrated cases, lip protrusion was improved by en-masse bodily retraction of the anterior teeth (>8 mm) using temporary anchorage devices. Three-dimensional cone-beam computed tomography showed that the maxillary incisor roots were approximated to the incisive canal after maximum retraction. One central incisor root was in direct contact with the incisive canal with severe root resorption, but tooth vitality and the overall occlusion were stable in the long term without any sensory dysfunction. The apparent root resorption may be mainly related to the large amounts of anterior retraction and root movement in the 2 patients. However, the anatomic location of the incisive canal and the possibilities of its invasion after tooth movement should be closely monitored when maximum retraction is planned, to prevent potential complications.

  9. The effect of canine disimpaction performed with temporary anchorage devices (TADs) before comprehensive orthodontic treatment to avoid root resorption of adjacent teeth (United States)

    Heravi, Farzin; Shafaee, Hooman; Forouzanfar, Ali; Zarch, Seyed Hossein Hoseini; Merati, Mohsen


    ABSTRACT Objective: The aim of this study was to evaluate the movement of impacted canines away from the roots of neighboring teeth before full-mouth bracket placement, performed by means of TADs to decrease undesired side effects on adjacent teeth. Methods: The study sample consisted of 34 palatally impacted canines, being 19 in the experimental group and 15 in the control group. In the experimental group, before placement of brackets, the impacted canine was erupted by means of miniscrews. In the control group, after initiation of comprehensive orthodontics, canine disimpaction was performed by means of a cantilever spring soldered to a palatal bar. At the end of treatment, volume of lateral incisors and canine root resorption were measured and compared by means of a CBCT-derived tridimensional model. Visual Analogue Scale (VAS) score, bleeding on probing (BOP) and gingival index (GI) were recorded. Clinical success rate was also calculated. Results: The volume of root resorption of lateral teeth in the control group was significantly greater than in the experimental group (p < 0.001). At the end of treatment, VAS score, GI and BOP were not significantly different between the two groups. Conclusion: Based on our results, it seems that disimpaction of canines and moving them to the arch can be done successfully carried out with minimal side effects by means of skeletal anchorage. PMID:27275617

  10. Independent EEG sources are dipolar

    National Research Council Canada - National Science Library

    Delorme, Arnaud; Palmer, Jason; Onton, Julie; Oostenveld, Robert; Makeig, Scott


    Independent component analysis (ICA) and blind source separation (BSS) methods are increasingly used to separate individual brain and non-brain source signals mixed by volume conduction in electroencephalographic (EEG...

  11. Logical independence and quantum randomness

    Energy Technology Data Exchange (ETDEWEB)

    Paterek, T; Kofler, J; Aspelmeyer, M; Zeilinger, A; Brukner, C [Institute for Quantum Optics and Quantum Information, Austrian Academy of Sciences, Boltzmanngasse 3, A-1090 Vienna (Austria); Prevedel, R; Klimek, P [Faculty of Physics, University of Vienna, Boltzmanngasse 5, A-1090 Vienna (Austria)], E-mail:


    We propose a link between logical independence and quantum physics. We demonstrate that quantum systems in the eigenstates of Pauli group operators are capable of encoding mathematical axioms and show that Pauli group quantum measurements are capable of revealing whether or not a given proposition is logically dependent on the axiomatic system. Whenever a mathematical proposition is logically independent of the axioms encoded in the measured state, the measurement associated with the proposition gives random outcomes. This allows for an experimental test of logical independence. Conversely, it also allows for an explanation of the probabilities of random outcomes observed in Pauli group measurements from logical independence without invoking quantum theory. The axiomatic systems we study can be completed and are therefore not subject to Goedel's incompleteness theorem.

  12. Provisional coverage for independent workers


    Díaz, Luis Eduardo


    The study examines how, from the traditional work of the independent artisan, we have moved to autonomous work integrated within networks of specialized businesses. This modality is owed not only to the manner in which labor is organized today, to government stimuli, to actions of multilaterals, but also to unemployment. With the purpose of humanizing independent work and rationalizing business costs, an intermediate category of autonomous worker has been created; the semi-dependent who...

  13. Growth hormone response to growth hormone-releasing peptide-2 in growth hormone-deficient Little mice


    PERONI, CIBELE N.; Cesar Y. Hayashida; Nancy Nascimento; LONGUINI, VIVIANE C.; Toledo, Rodrigo A.; Paolo Bartolini; Bowers, Cyril Y.; Toledo,Sergio P. A.


    OBJECTIVE: To investigate a possible direct, growth hormone-releasing, hormone-independent action of a growth hormone secretagogue, GHRP-2, in pituitary somatotroph cells in the presence of inactive growth hormone-releasing hormone receptors. MATERIALS AND METHODS: The responses of serum growth hormone to acutely injected growth hormone-releasing P-2 in lit/litmice, which represent a model of GH deficiency arising frommutated growth hormone-releasing hormone-receptors, were compared to those ...

  14. Growth Hormone (United States)

    ... AACC products and services. Advertising & Sponsorship: Policy | Opportunities Growth Hormone Share this page: Was this page helpful? Also known as: GH; Human Growth Hormone; HGH; Somatotropin; Growth Hormone Stimulation Test; Growth ...

  15. Independent Research and Independent Exploratory Development FY 1985 (United States)


    complexity and cerebral sensory interaction. Personality and Individual Differences , 6(2), 253-261. Federico, P-A (1985). Individual differences in concept...learning and brain event-related potentials. Personality and Individual Differences , 6(2), 243-252. INDEPENDENT EXPLORATORY DEVELOPMENT PUBLICATIONS

  16. S100A8/A9 (calprotectin negatively regulates G2/M cell cycle progression and growth of squamous cell carcinoma.

    Directory of Open Access Journals (Sweden)

    Ali Khammanivong

    Full Text Available Malignant transformation results in abnormal cell cycle regulation and uncontrolled growth in head and neck squamous cell carcinoma (HNSCC and other cancers. S100A8/A9 (calprotectin is a calcium-binding heterodimeric protein complex implicated in cell cycle regulation, but the specific mechanism and role in cell cycle control and carcinoma growth are not well understood. In HNSCC, S100A8/A9 is downregulated at both mRNA and protein levels. We now report that downregulation of S100A8/A9 correlates strongly with a loss of cell cycle control and increased growth of carcinoma cells. To show its role in carcinogenesis in an in vitro model, S100A8/A9 was stably expressed in an S100A8/A9-negative human carcinoma cell line (KB cells, HeLa-like. S100A8/A9 expression increases PP2A phosphatase activity and p-Chk1 (Ser345 phosphorylation, which appears to signal inhibitory phosphorylation of mitotic p-Cdc25C (Ser216 and p-Cdc2 (Thr14/Tyr15 to inactivate the G2/M Cdc2/cyclin B1 complex. Cyclin B1 expression then downregulates and the cell cycle arrests at the G2/M checkpoint, reducing cell division. As expected, S100A8/A9-expressing cells show both decreased anchorage-dependent and -independent growth and mitotic progression. Using shRNA, silencing of S100A8/A9 expression in the TR146 human HNSCC cell line increases growth and survival and reduces Cdc2 inhibitory phosphorylation at Thr14/Tyr15. The level of S100A8/A9 endogenous expression correlates strongly with the reduced p-Cdc2 (Thr14/Tyr14 level in HNSCC cell lines, SCC-58, OSCC-3 and UMSCC-17B. S100A8/A9-mediated control of the G2/M cell cycle checkpoint is, therefore, a likely suppressive mechanism in human squamous cell carcinomas and may suggest new therapeutic approaches.

  17. Human skin: an independent peripheral endocrine organ. (United States)

    Zouboulis, C C


    The historical picture of the endocrine system as a set of discrete hormone-producing organs has been substituted by organs regarded as organized communities in which the cells emit, receive and coordinate molecular signals from established endocrine organs, other distant sources, their neighbors, and themselves. In this wide sense, the human skin and its tissues are targets as well as producers of hormones. Although the role of hormones in the development of human skin and its capacity to produce and release hormones are well established, little attention has been drawn to the ability of human skin to fulfil the requirements of a classic endocrine organ. Indeed, human skin cells produce insulin-like growth factors and -binding proteins, propiomelanocortin derivatives, catecholamines, steroid hormones and vitamin D from cholesterol, retinoids from diet carotenoids, and eicosanoids from fatty acids. Hormones exert their biological effects on the skin through interaction with high-affinity receptors, such as receptors for peptide hormones, neurotransmitters, steroid hormones and thyroid hormones. In addition, the human skin is able to metabolize hormones and to activate and inactivate them. These steps are overtaken in most cases by different skin cell populations in a coordinated way indicating the endocrine autonomy of the skin. Characteristic examples are the metabolic pathways of the corticotropin-releasing hormone/propiomelanocortin axis, steroidogenesis, vitamin D, and retinoids. Hormones exhibit a wide range of biological activities on the skin, with major effects caused by growth hormone/insulin-like growth factor-1, neuropeptides, sex steroids, glucocorticoids, retinoids, vitamin D, peroxisome proliferator-activated receptor ligands, and eicosanoids. At last, human skin produces hormones which are released in the circulation and are important for functions of the entire organism, such as sex hormones, especially in aged individuals, and insulin-like growth

  18. Introduction to algebraic independence theory

    CERN Document Server

    Philippon, Patrice


    In the last five years there has been very significant progress in the development of transcendence theory. A new approach to the arithmetic properties of values of modular forms and theta-functions was found. The solution of the Mahler-Manin problem on values of modular function j(tau) and algebraic independence of numbers pi and e^(pi) are most impressive results of this breakthrough. The book presents these and other results on algebraic independence of numbers and further, a detailed exposition of methods created in last the 25 years, during which commutative algebra and algebraic geometry exerted strong catalytic influence on the development of the subject.

  19. CFRP筋锚固体系研究与应用现状%Research and Application Situation of CFRP Tendon Anchorage System

    Institute of Scientific and Technical Information of China (English)

    刘荣桂; 李明君; 蔡东升; 刘德鑫


    为促进碳纤维增强复合材料(CFRP)这一具有密度小、抗拉强度高、抗疲劳、耐腐蚀等特性材料的研究工作与在土木工程结构中的实际应用,主要介绍了各国有关CFRP筋及其锚具研究和应用的最新进展,分别对粘结型、夹片型、复合型3类现有的主要类型锚具的锚固机理、代表性试验研究和数值分析等方面做了整理和归纳,并提出了锚具开发和应用的一些关键问题和建议.%In order to promote the future research and application of carbon fiber reinforced polymer (CFRP) for civil engineering structures, with the characteristics of low specific gravity, high tensile strength, high fatigue resistance and corrosion resistance, an introduction was given on the latest research and application progress of CFRP tendon and anchors for all countries. The anchorage mechanism, typical experiment investigations and numerical analysis of exist main types of anchors, including bond-type anchor, wedge-type anchor and wedge-bond anchor, were also classified and summarized. Finally, some critical problems and advices in anchor development and utilization were provided.

  20. 3-(Dipropylamino)-5-hydroxybenzofuro[2,3-f]quinazolin-1(2H)-one (DPA-HBFQ-1) plays an inhibitory role on breast cancer cell growth and progression. (United States)

    Rizza, Pietro; Pellegrino, Michele; Caruso, Anna; Iacopetta, Domenico; Sinicropi, Maria Stefania; Rault, Sylvain; Lancelot, Jean Charles; El-Kashef, Hussein; Lesnard, Aurelien; Rochais, Christophe; Dallemagne, Patrick; Saturnino, Carmela; Giordano, Francesca; Catalano, Stefania; Andò, Sebastiano


    A series of unknown 3-(alkyl(dialkyl)amino)benzofuro[2,3-f]quinazolin-1(2H)-ones 4-17 has been synthesized as new ellipticine analogs, in which the carbazole moiety and the pyridine ring were replaced by a dibenzofuran residue and a pyrimidine ring, respectively. The synthesis of these benzofuroquinazolinones 4-17 was performed in a simple one-pot reaction using 3-aminodibenzofuran or its 2-methoxy derivative, as starting materials. From 3-(dipropylamino)-5-methoxybenzofuro[2,3-f] quinazolin-1(2H)-one (13), we prepared 3-(dipropylamino)-5-hydroxybenzofuro[2,3-f]quinazolin-1(2H)-one (18), referred to as DPA-HBFQ-1. The cytotoxic activities of all the synthesized compounds, tested in different human breast cancer cell lines, revealed that DPA-HBFQ-1 was the most active compound. In particular, the latter was able to inhibit anchorage-dependent and -independent cell growth and to induce apoptosis in estrogen receptor alpha (ERα)-positive and -negative breast cancer cells. It did not affect proliferation and apoptotic responses in MCF-10A normal breast epithelial cells. The observed effects have been ascribed to an enhanced p21(Cip1/WAF1) expression in a p53-dependent manner of tumor suppressor and to a selective inhibition of human topoisomerase II. In addition, DPA-HBFQ-1 exerted growth inhibitory effects also in other cancer cell lines, even though with a lower cytotoxic activity. Our results indicate DPA-HBFQ-1 as a good candidate to be useful as cancer therapeutic agent, particularly for breast cancer.

  1. Model-independent tests of cosmic gravity. (United States)

    Linder, Eric V


    Gravitation governs the expansion and fate of the universe, and the growth of large-scale structure within it, but has not been tested in detail on these cosmic scales. The observed acceleration of the expansion may provide signs of gravitational laws beyond general relativity (GR). Since the form of any such extension is not clear, from either theory or data, we adopt a model-independent approach to parametrizing deviations to the Einstein framework. We explore the phase space dynamics of two key post-GR functions and derive a classification scheme, and an absolute criterion on accuracy necessary for distinguishing classes of gravity models. Future surveys will be able to constrain the post-GR functions' amplitudes and forms to the required precision, and hence reveal new aspects of gravitation.

  2. Strong sequences and independent sets

    Directory of Open Access Journals (Sweden)

    Joanna Jureczko


    Full Text Available A family $\\mathcal{S} \\in \\mathcal{P}(\\omega$ is \\textit{an independent family} if for each pair $\\mathcal{A, B}$ of disjoint finite subsets of $\\mathcal{S}$ the set $\\bigcap \\mathcal{A} \\cap (\\omega \\setminus \\bigcup \\mathcal{B}$ is nonempty. The fact that there is an independent family on $\\omega$ of size continuum was proved by Fichtenholz and Kantorowicz in \\cite{FK}. If we substitute $\\mathcal{P}(\\omega$ by a set $(X, r$ with arbitrary relation \\textit{r} it is natural question about existence and length of an independent set on $(X, r$. In this paper special assumptions of such existence will be considered. On the other hand in 60s' of the last century the strong sequences method was introduced by Efimov. He used it for proving some famous theorems in dyadic spaces like: Marczewski theorem on cellularity, Shanin theorem on a calibre, Esenin-Volpin theorem and others. In this paper there will be considered: length of strong sequences, the length of independent sets and other well known cardinal invariants and there will be examined inequalities among them.

  3. Boston: Cradle of American Independence (United States)

    Community College Journal, 2004


    The 2005 American Association of Community Colleges Annual Convention will be held April 6-9 in Boston. While thoroughly modern, the iconic city's identity is firmly rooted in the past. As the cradle of American independence, Boston's long history is an integral part of the American fabric. Adams, Revere, Hancock are more than historical figures;…

  4. Background Independent String Field Theory

    CERN Document Server

    Bars, Itzhak


    We develop a new background independent Moyal star formalism in bosonic open string field theory. The new star product is formulated in a half-phase-space, and because phase space is independent of any background fields, the interactions are background independent. In this basis there is a large amount of symmetry, including a supersymmetry OSp(d|2) that acts on matter and ghost degrees of freedom, and simplifies computations. The BRST operator that defines the quadratic kinetic term of string field theory may be regarded as the solution of the equation of motion A*A=0 of a purely cubic background independent string field theory. We find an infinite number of non-perturbative solutions to this equation, and are able to associate them to the BRST operator of conformal field theories on the worldsheet. Thus, the background emerges from a spontaneous-type breaking of a purely cubic highly symmetric theory. The form of the BRST field breaks the symmetry in a tractable way such that the symmetry continues to be us...

  5. Cobordism Independence of Grassmann Manifolds

    Indian Academy of Sciences (India)

    Ashish Kumar Das


    This note proves that, for $F=\\mathbb{R},\\mathbb{C}$ or $\\mathbb{H}$, the bordism classes of all non-bounding Grassmannian manifolds $G_k(F^{n+k})$, with < and having real dimension , constitute a linearly independent set in the unoriented bordism group $\\mathfrak{N}_d$ regarded as a $\\mathbb{Z}_2$-vector space.

  6. Testing bivariate independence and normality

    NARCIS (Netherlands)

    Kallenberg, W.C.M.; Ledwina, Teresa; Rafajlowicz, Ewaryst


    In many statistical studies the relationship between two random variables X and Y is investigated and in particular the question whether X and Y are independent and normally distributed is of interest. Smooth tests may be used for testing this. They consist of several components, the first measuring

  7. Glycerol-3-phosphate acyltranferase-2 behaves as a cancer testis gene and promotes growth and tumorigenicity of the breast cancer MDA-MB-231 cell line.

    Directory of Open Access Journals (Sweden)

    Magali Pellon-Maison

    Full Text Available The de novo synthesis of glycerolipids in mammalian cells begins with the acylation of glycerol-3-phosphate, catalyzed by glycerol-3-phosphate acyltransferase (GPAT. GPAT2 is a mitochondrial isoform primarily expressed in testis under physiological conditions. Because it is aberrantly expressed in multiple myeloma, it has been proposed as a novel cancer testis gene. Using a bioinformatics approach, we found that GPAT2 is highly expressed in melanoma, lung, prostate and breast cancer, and we validated GPAT2 expression at the protein level in breast cancer by immunohistochemistry. In this case GPAT2 expression correlated with a higher histological grade. 5-Aza-2' deoxycytidine treatment of human cells lines induced GPAT2 expression suggesting epigenetic regulation of gene expression. In order to evaluate the contribution of GPAT2 to the tumor phenotype, we silenced its expression in MDA-MB-231 cells. GPAT2 knockdown diminished cell proliferation, anchorage independent growth, migration and tumorigenicity, and increased staurosporine-induced apoptosis. In contrast, GPAT2 over-expression increased cell proliferation rate and resistance to staurosporine-induced apoptosis. To understand the functional role of GPAT2, we performed a co-expression analysis in mouse and human testis and found a significant association with semantic terms involved in cell cycle, DNA integrity maintenance, piRNA biogenesis and epigenetic regulation. Overall, these results indicate the GPAT2 would be directly associated with the control of cell proliferation. In conclusion, we confirm GPAT2 as a cancer testis gene and that its expression contributes to the tumor phenotype of MDA-MB-231 cells.

  8. Green tea polyphenol EGCG suppresses lung cancer cell growth through upregulating miR-210 expression caused by stabilizing HIF-1α. (United States)

    Wang, Hong; Bian, Shengjie; Yang, Chung S


    (-)-Epigallocatechin-3-gallate (EGCG) has been reported to affect many cellular regulatory pathways. This study aims to determine whether EGCG could target microRNA (miRNA), one of the mechanisms for cells to achieve subtle change in multiple targets. We found that, in both human and mouse lung cancer cells in culture, EGCG specifically upregulated the expression of miR-210, a major miRNA regulated by HIF-1α. Furthermore, we found that overexpression of miR-210 led to reduced cell proliferation rate and anchorage-independent growth as well as reduced sensitivity to EGCG. On the mechanisms of miR-210 regulation by EGCG, we demonstrated that the regulation was mediated through the hypoxia-response element in miR-210 promoter. Consistently, the upregulation of miR-210 was found to be correlated with the stabilized HIF-1α in lung cancer cell lines after EGCG treatment. This EGCG-induced stabilization of HIF-1α was further shown by the stabilization of HA-tagged HIF-1α but not the P402A/P564A-mutated HIF-1α by EGCG, suggesting that EGCG targets the oxygen-dependent degradation (ODD) domain. Direct evidence was obtained by affinity binding assay showing that EGCG specifically binds HIF-1α with a K(d) = 3.47 μM. This result suggests that EGCG binding interferes with the hydroxylation of key Pro residues in the ODD domain, preventing HIF-1α from the Pro hydroxylation-dependent ubiquitination and subsequent proteosome-mediated degradation. In summary, our results demonstrated, for the first time, the elevation of miR-210 by EGCG in lung cancer cell lines and this is mediated by the stabilization of HIF-1α. This event contributes to the anticancer activity of EGCG.

  9. Reinforcing of deposit slopes of Xiaowan Hydropower Station and application of prestressed anchorage cables%小湾水电站堆积体边坡支护与锚索技术应用

    Institute of Scientific and Technical Information of China (English)

    张德圣; 姜玉松; 吴诗勇


    With regard to the deposit slopes of Xiaowan Hydropower Station, the relevant reinforcing measures were analyzed, and the application of prestressed anchorage cables was highlighted. The results indicate that the slope reinforcements in the study area comprehensively adopt engineering protection and ecological protection techniques. The pre-stressing anchorage cables are the principal part of the engineering, and their drilling and grouting are the difficulty and keystone of the anchorage technology. The technology of concentric drilling and eccentric drilling with pipes can availably solve boring problem. By wrapping geotextile and thin canvas outside the prestressed steel strand, it can make concrete calculi protect steel strand of tensile section and reduce grouting quantity so as to avoid grouting waste.%分析小湾水电站堆积体边坡支护措施,研究预应力锚索技术的应用.分析认为,研究区边坡支护综合运用了工程护坡和生态护坡等边坡处理技术,预应力锚索是其主体工程,锚索孔钻孔和灌浆是该技术应用中的难点和重点,使用偏心跟管钻进技术和同心跟管钻进技术能有效解决钻孔难以成孔的问题;通过在锚索体外裹土工布和细帆布的方法,既保证了水泥结石对自由段锚索体的保护,又减少了浆量损耗,避免浆体浪费.

  10. Growth Disorders (United States)

    ... because their parents are. But some children have growth disorders. Growth disorders are problems that prevent children from developing ... or other features. Very slow or very fast growth can sometimes signal a gland problem or disease. ...

  11. Central bank independence and its effect on money market stability

    Directory of Open Access Journals (Sweden)

    MSc. Anera Alishani


    Full Text Available Since 1990s many countries have moved toward greater central bank independence (CBI by either amending their Central Bank’s laws or writing them de novo. Also countries of Western Balkans and many other transition countries have moved toward greater CBI. There are many potential benefits associated with greater CBI, and one of them is stable growth of money and liquidity. For a given level of money market development the hypothesis is that a more independent CB is likely to promote more stable growth of money supply (Dželetović et al., 2008. As a result the main research task of this work is to estimate the effects of CBI on money market growth for five Western Balkans countries and five other European transition countries. Because the empirical studies were very limited for the relationship between CBI and money market growth, there were no clear conclusions. In addition, there were different measuring methodologies that attempt to quantify the extent of legal and actual CBI. Related to the main research task, this dissertation has examined the effects of CBI on money market stability (proxied by bank deposit growth for a sample of 10 countries for a period from 1999-2009 by using fixed effect model. Through this methodology different regressions have been estimated, but the results were not robust and there are no clear finding on the relationship between CBI and money market growth.

  12. 钢锚梁式钢-混组合索塔锚固体系设计与分析%Design and Analysis of Steel-concrete Composite Anchorage Structure with Steel Anchor Beam

    Institute of Scientific and Technical Information of China (English)

    苗通; 孙蕊鑫


    A bridge is a twin towers and double cable plane prestressed concrete girder cable -stayed bridge with a span arrangement of (130 +300 +130)m,and the tower type is inverted Y and the Steel -concrete Composite anchorage structure with Steel Anchor Beam is used to anchorage the cable of end of the tower.Among this type anchorage system,the anchor boxes have been welded on both sides of the steel anchor beam,at the same time, using steel bracket to replace traditional concrete corbel structure.In this paper,the characteristics of this kind of anchor system has been introduced and the stress situation of this kind of anchor system has been analyzed u-sing the finite element method.The research conclusion can provide a reference for the design of this type of ca-ble pylon anchorage system.%某斜拉桥主桥是一座跨径布置为(130m +300m +130m)的双塔双索面预应力混凝土梁斜拉桥,索塔采用倒 Y 型,斜拉索在桥塔端采用新型空间索面钢锚梁式钢-混组合索塔锚固体系进行锚固。该型锚固体系将锚箱焊在钢锚梁两侧,同时采用钢牛腿替换传统的混凝土牛腿结构,提高了施工速度,改善了结构受力。介绍了该种锚固体系的特点,并采用有限元方法对改型索塔锚固体系的受力情况进行了分析,可为该类型索塔锚固体系设计提供参考。

  13. Design of cable-girder anchorage system scheme in self-anchored suspension bridge%自锚式悬索桥缆-梁锚固系统方案设计

    Institute of Scientific and Technical Information of China (English)



    本文根据已建以及待建自锚式悬索桥工程实例,将自锚式悬索桥工程中主缆在加劲梁梁端的锚固方案进行了总结分析,从施工方面、经济性以及美观性等方面指出了各种锚固方式的优缺点以及适应性。按照锚体材料的不同将现有锚固方式重新进行了分类,综合现有的分类方式提出了一套锚固系统方案设计流程。这种设计流程条理清楚、直观易理解,为今后的自锚式悬索桥主缆锚固系统设计提供指导,快速的形成锚固系统方案,提高设计效率,并获得更好的经济性和美观性。%According to the engineering examples of the self -anchored suspension bridges built and to be built , the cable -girder an-chored projects are summarized and analyzed.From the construction , economy and aesthetics aspects , the advantages adaptability of vari-ous ways of anchoring and are pointed out.According to the different materials of the existing anchorage , the way of anchoring is re -clas-sified and a set of anchor system design process is put forward based on the classification of the existing anchorage systems .This design process is clear , intuitive and easy to understand and can provide guidance for the design of self -anchored suspension bridge main cable anchorage system in the future.Using this design process , anchorage system scheme will be quickly put forward , the design efficiency can be improved and the bridge will be more economic and more beautiful.

  14. Electrochemical island growth (United States)

    Guo, Lian

    The ability to independently dictate the shape and crystal orientation of islands in electrocrystallization remains a significant challenge. The main reason for this is that the complex interplay between the substrate, nucleation, and surface chemistry are not fully understood. Here the kinetics of 3D island growth for copper on ruthenium oxide is studied. The small nucleation overpotential leads to enhanced lateral growth and the formation of hexagonal, disk-shaped islands. The amorphous substrate allows the nuclei to achieve the thermodynamically favorable orientation, i.e. a surface normal. Island growth follows power law kinetics in both lateral and vertical directions. At shorter times, the two growth exponents are equal to 1/2 whereas at longer times lateral growth slows down while vertical growth speeds up. Accordingly, a growth mechanism is proposed, wherein the lateral growth of disk-shaped islands is initiated by attachment of Cu adatoms on the ruthenium oxide surface onto the island periphery while vertical growth is initiated by 2D nucleation on the top terrace and followed by lateral step propagation. These results indicate three criteria for enhanced lateral growth in electrodeposition: (i) a substrate that leads to a small nucleation overpotential, (ii) fast adatom surface diffusion on substrate to promote lateral growth, and (iii) preferential anion adsorption to stabilize the basal plane. The surface roughness evolution, during isolated island growth, island coalescence, and continuous film growth, has also been studied as a function of island shape and island density. It is shown that the surface width wsat(l,t) initially follows anomalous scaling in the isolated island growth regime but exhibits normal scaling during the early stages of continuous film growth. Furthermore, the short length scale roughness is dependent primarily on island shape while the long length scale roughness is dependent on island density. Electrochemical deposition of


    Directory of Open Access Journals (Sweden)

    Coroiu Sorina


    Full Text Available The empirical evidence upon the macroeconomic performances of the independent central banks do not always have been successfully. In some cases, the consistency of the indices based on the interpretation of central banks statues used for measuring the degree of central bank independence is controversial, particularly for some of the indices. Moreover, the correlations between central bank independence and macroeconomic performance variables are not always confirmed, the causal relationship between central bank independence and inflation is controversial, and the higher disinflation costs, as a result of a higher sacrifice ratio correlated with the degree of independence is controversial, too. The effects of central bank independence upon macroeconomic performances focalized upon the empirical evidence of inflation, output or economic grouth and the disinflation costs. This is due to the lack of studies vis - vis of relationship between central bank independence and macroeconomic performances regarding some variables like interest rates and budgetary deficits. Specialists consider inflation and output as the main determinats of the social welfare. The economic literature regarding this fact suggests that the central bank is seen as a free lunch institution. This hypothesis sustains that independent central banks will have social benefits in terms of lower inflation rates, but without any costs in terms of the real macroeconomic performances as a higher output volatility or a lower economic growth. In this article we provide a qualitative analyses regarding the relationship between central bank independence and macroeconomic performances. For this purpose the authors used the new index for measuring central bank independence and inflation targeting based on three pillars: political and legal central bank independence, central bank governance and conduct of monetary policy, central bank transparency and accountability. For estimating the

  16. Abduction of Toe-excavation Induced Failure Process from LEM and FDM for a Dip Slope with Rock Anchorage in Taiwan (United States)

    Huang, W.-S.; Lin, M.-L.; Liu, H.-C.; Lin, H.-H.


    On April 25, 2010, without rainfall and earthquake triggering a massive landslide (200000 m3) covered a 200m stretch of Taiwan's National Freeway No. 3, killing 4 people, burying three cars and destroying a bridge. The failure mode appears to be a dip-slope type failure occurred on a rock anchorage cut slope. The strike of Tertiary sedimentary strata is northeast-southwest and dip 15˚ toward southeast. Based on the investigations of Taiwan Geotechnical Society, there are three possible factors contributing to the failure mechanism as follow:(1) By toe-excavation during construction in 1998, the daylight of the sliding layer had induced the strength reduction in the sliding layer. It also caused the loadings of anchors increased rapidly and approached to their ultimate capacity; (2) Although the excavated area had stabilized soon with rock anchors and backfills, the weathering and groundwater infiltration caused the strength reduction of overlying rock mass; (3) The possible corrosion and age of the ground anchors deteriorate the loading capacity of rock anchors. Considering the str