WorldWideScience

Sample records for centrally-assessed erbb2 status

  1. Adjuvant letrozole versus tamoxifen according to centrally-assessed ERBB2 status for postmenopausal women with endocrine-responsive early breast cancer: supplementary results from the BIG 1-98 randomised trial

    DEFF Research Database (Denmark)

    Regan, M.M.; Lykkesfeldt, A.E.; Dell'Orto, P.

    2008-01-01

    as ERBB2-positive. In 3533 patients with tumours confirmed to express ER, DFS was poorer in patients with ERBB2-positive tumours (n=239) than in those with ERBB2-negative tumours (n=3294; HR 2-09 [95% CI 1.59-2 -76]; pevidence of heterogeneity in the treatment effect...

  2. Integrated assessment of potential value of erbB-2 amplification or expression status as novel therapy target in Chinese children and adolescents with osteosarcoma

    Institute of Scientific and Technical Information of China (English)

    SHANG Jian; BI Zheng-gang; JI Hong-fei; WANG Wen-bo

    2009-01-01

    Background Targeted tumor therapies have been making rapid progress in recent years, and the erbB-2 oncogene is a suitable target. There was much discussion about the level of erbB-2 in osteosarcoma. The aim of this study was to investigate the erbB-2 amplification or expression status in osteosarcoma. Methods Fluorescence in situ hybridization (FISH) and DNA probes for erbB-2 and centromere 17 were used to examine the erbB-2 gene amplification status in 32 osteosarcoma samples, and expression of erbB-2 was analyzed by immunohistochemistry (IHC) and reverse transcription-polymerase chain reaction (RT-PCR).Results None of the 32 osteosarcomas was observed by FISH to have the erbB-2 gene amplified, and no distinguishable membrane staining was seen in any case yet, nevertheless, erbB-2 overexpression was present in 6 tumor samples by RT-PCR.Conclusions The status of erbB-2 gene amplification and membrane overexpression is rare in osteosarcomas, and might suggest that the erbB-2 target agent should not be applied to osteosarcomas as single treatment .

  3. Genome profiling of ERBB2-amplified breast cancers

    Directory of Open Access Journals (Sweden)

    Ayed Farhat

    2010-10-01

    Full Text Available Abstract Background Around 20% of breast cancers (BC show ERBB2 gene amplification and overexpression of the ERBB2 tyrosine kinase receptor. They are associated with a poor prognosis but can benefit from targeted therapy. A better knowledge of these BCs, genomically and biologically heterogeneous, may help understand their behavior and design new therapeutic strategies. Methods We defined the high resolution genome and gene expression profiles of 54 ERBB2-amplified BCs using 244K oligonucleotide array-comparative genomic hybridization and whole-genome DNA microarrays. Expression of ERBB2, phosphorylated ERBB2, EGFR, IGF1R and FOXA1 proteins was assessed by immunohistochemistry to evaluate the functional ERBB2 status and identify co-expressions. Results First, we identified the ERBB2-C17orf37-GRB7 genomic segment as the minimal common 17q12-q21 amplicon, and CRKRS and IKZF3 as the most frequent centromeric and telomeric amplicon borders, respectively. Second, GISTIC analysis identified 17 other genome regions affected by copy number aberration (CNA (amplifications, gains, losses. The expression of 37 genes of these regions was deregulated. Third, two types of heterogeneity were observed in ERBB2-amplified BCs. The genomic profiles of estrogen receptor-postive (ER+ and negative (ER- ERBB2-amplified BCs were different. The WNT/β-catenin signaling pathway was involved in ER- ERBB2-amplified BCs, and PVT1 and TRPS1 were candidate oncogenes associated with ER+ ERBB2-amplified BCs. The size of the ERBB2 amplicon was different in inflammatory (IBC and non-inflammatory BCs. ERBB2-amplified IBCs were characterized by the downregulated and upregulated mRNA expression of ten and two genes in proportion to CNA, respectively. IHC results showed (i a linear relationship between ERBB2 gene amplification and its gene and protein expressions with a good correlation between ERBB2 expression and phosphorylation status; (ii a potential signaling cross-talk between

  4. Combined inhibition of ErbB1/2 and Notch receptors effectively targets breast ductal carcinoma in situ (DCIS stem/progenitor cell activity regardless of ErbB2 status.

    Directory of Open Access Journals (Sweden)

    Gillian Farnie

    Full Text Available Pathways involved in DCIS stem and progenitor signalling are poorly understood yet are critical to understand DCIS biology and to develop new therapies. Notch and ErbB1/2 receptor signalling cross talk has been demonstrated in invasive breast cancer, but their role in DCIS stem and progenitor cells has not been investigated. We have utilised 2 DCIS cell lines, MCF10DCIS.com (ErbB2-normal and SUM225 (ErbB2-overexpressing and 7 human primary DCIS samples were cultured in 3D matrigel and as mammospheres in the presence, absence or combination of the Notch inhibitor, DAPT, and ErbB1/2 inhibitors, lapatinib or gefitinib. Western blotting was applied to assess downstream signalling. In this study we demonstrate that DAPT reduced acini size and mammosphere formation in MCF10DCIS.com whereas there was no effect in SUM225. Lapatinb reduced acini size and mammosphere formation in SUM225, whereas mammosphere formation and Notch1 activity were increased in MCF10DCIS.com. Combined DAPT/lapatinib treatment was more effective at reducing acini size in both DCIS cell lines. Mammosphere formation in cell lines and human primary DCIS was reduced further by DAPT/lapatinib or DAPT/gefitinib regardless of ErbB2 receptor status. Our pre-clinical human models of DCIS demonstrate that Notch and ErbB1/2 both play a role in DCIS acini growth and stem cell activity. We report for the first time that cross talk between the two pathways in DCIS occurs regardless of ErbB2 receptor status and inhibition of Notch and ErbB1/2 was more efficacious than either alone. These data provide further understanding of DCIS biology and suggest treatment strategies combining Notch and ErbB1/2 inhibitors should be investigated regardless of ErbB2 receptor status.

  5. Combined inhibition of ErbB1/2 and Notch receptors effectively targets breast ductal carcinoma in situ (DCIS) stem/progenitor cell activity regardless of ErbB2 status.

    Science.gov (United States)

    Farnie, Gillian; Willan, Pamela M; Clarke, Robert B; Bundred, Nigel J

    2013-01-01

    Pathways involved in DCIS stem and progenitor signalling are poorly understood yet are critical to understand DCIS biology and to develop new therapies. Notch and ErbB1/2 receptor signalling cross talk has been demonstrated in invasive breast cancer, but their role in DCIS stem and progenitor cells has not been investigated. We have utilised 2 DCIS cell lines, MCF10DCIS.com (ErbB2-normal) and SUM225 (ErbB2-overexpressing) and 7 human primary DCIS samples were cultured in 3D matrigel and as mammospheres in the presence, absence or combination of the Notch inhibitor, DAPT, and ErbB1/2 inhibitors, lapatinib or gefitinib. Western blotting was applied to assess downstream signalling. In this study we demonstrate that DAPT reduced acini size and mammosphere formation in MCF10DCIS.com whereas there was no effect in SUM225. Lapatinb reduced acini size and mammosphere formation in SUM225, whereas mammosphere formation and Notch1 activity were increased in MCF10DCIS.com. Combined DAPT/lapatinib treatment was more effective at reducing acini size in both DCIS cell lines. Mammosphere formation in cell lines and human primary DCIS was reduced further by DAPT/lapatinib or DAPT/gefitinib regardless of ErbB2 receptor status. Our pre-clinical human models of DCIS demonstrate that Notch and ErbB1/2 both play a role in DCIS acini growth and stem cell activity. We report for the first time that cross talk between the two pathways in DCIS occurs regardless of ErbB2 receptor status and inhibition of Notch and ErbB1/2 was more efficacious than either alone. These data provide further understanding of DCIS biology and suggest treatment strategies combining Notch and ErbB1/2 inhibitors should be investigated regardless of ErbB2 receptor status.

  6. Determining HER2 (ERBB2) amplification status in women with breast cancer: final results from the Australian in situ hybridisation program.

    Science.gov (United States)

    Morey, Adrienne L; Brown, Belinda; Farshid, Gelareh; Fox, Stephen B; Francis, Glenn D; McCue, Glenda; von Neumann-Cosel, Vita; Bilous, Michael

    2016-10-01

    Appropriate and accurate determination of HER2 status in women with breast cancer is critical for stratifying anti-HER2 therapies, and for access to subsidised treatment in the Australian setting. We conducted a regulated, nationwide program providing HER2 in situ hybridisation (ISH) testing for patients with newly diagnosed breast cancer. Cases with equivocal or non-diagnostic ISH test results at the local laboratory were sent to a high volume central testing laboratory for analysis using fluorescence ISH (FISH). We tested 78,408 early breast cancers and 3469 metastatic cancers using ISH. Of these, 12,405 early breast cancers (15.8%) and 798 metastatic cancers (23.0%) were HER2 positive. During the testing period, the proportion of core biopsy samples increased, the number of repeat tests remained stable and testing turnaround time declined. Discordant 3+ IHC, ISH negative results dropped from 20% to 13% in early breast cancers and from 35% to 8% among metastatic breast cancers. Following central laboratory FISH testing only 87 samples remained non-diagnostic (1.9% of FISH-tested samples, 0.1% of the whole cohort), most being decalcified specimens. This is a successful story of a cohesive service determining HER2 status in women with breast cancer in a 'real-world' setting.

  7. Differential sensitivity of ERBB2 kinase domain mutations towards lapatinib.

    Directory of Open Access Journals (Sweden)

    Rama Krishna Kancha

    Full Text Available BACKGROUND: Overexpression of the ERBB2 kinase is observed in about one-third of breast cancer patients and the dual ERBB1/ERBB2 kinase inhibitor lapatinib was recently approved for the treatment of advanced ERBB2-positive breast cancer. Mutations in the ERBB2 receptor have recently been reported in breast cancer at diagnosis and also in gastric, colorectal and lung cancer. These mutations may have an impact on the clinical responses achieved with lapatinib in breast cancer and may also have a potential impact on the use of lapatinib in other solid cancers. However, the sensitivity of lapatinib towards clinically observed ERBB2 mutations is not known. METHODOLOGY/PRINCIPAL FINDINGS: We cloned a panel of 8 clinically observed ERBB2 mutations, established stable cell lines and characterized their sensitivity towards lapatinib and alternative ERBB2 inhibitors. Both lapatinib-sensitive and lapatinib-resistant ERBB2 mutations were observed. Interestingly, we were able to generate lapatinib resistance mutations in wt-ERBB2 cells incubated with lapatinib for prolonged periods of time. This indicates that these resistance mutations may also cause secondary resistance in lapatinib-treated patients. Lapatinib-resistant ERBB2 mutations were found to be highly resistant towards AEE788 treatment but remained sensitive towards the dual irreversible inhibitors CL-387785 and WZ-4002. CONCLUSIONS/SIGNIFICANCE: Patients harbouring certain ERBB2 kinase domain mutations at diagnosis may not benefit from lapatinib treatment. Moreover, secondary lapatinib resistance may develop due to kinase domain mutations. Irreversible ERBB2 inhibitors may offer alternative treatment options for breast cancer and other solid tumor patients harbouring lapatinib resistance mutations. In addition, these inhibitors may be of interest in the scenario of secondary lapatinib resistance.

  8. Effects of ERBB2 amplicon size and genomic alterations of chromosomes 1, 3, and 10 on patient response to trastuzumab in metastatic breast cancer.

    Science.gov (United States)

    Morrison, Larry E; Jewell, Susan S; Usha, Lydia; Blondin, Beth A; Rao, Ruta D; Tabesh, Bita; Kemper, Matthew; Batus, Marta; Coon, John S

    2007-04-01

    Trastuzumab is widely used for advanced breast cancer patients with ERBB2-amplified tumors. Nevertheless, over half of these patients do not have an objective response. One reason may be altered expression of genes that might compensate for ERBB2 inhibition. We previously mapped the gene-rich region of chromosome 17 telomeric to ERBB2, and reported considerable variability in the telomeric extent of the ERBB2 amplicon. Here we examined whether the variable amplicon size may be associated with patient response to trastuzumab. In addition, we looked at associations between response and several signaling pathway-related genes unrelated to the ERBB2 amplicon, including AKT3, PTEN, PIK3CA, and PTGS2. In 35 patients with ERBB2-amplified metastatic breast cancer, with 40% overall response to trastuzumab, fluorescence in situ hybridization identified the telomeric extent of the ERBB2 amplicon and the status of the several pathway-related genes. Objective response strongly correlated with the telomeric amplicon size, with 62% of patients with shorter amplicons responding, compared with only 7% of patients with longer amplicons (P = 0.0015). Abnormal copy number of PTGS2 was marginally associated with objective response (P = 0.066), while abnormal copy numbers of two reference loci, 1q25 and the chromosome 10 centromere, were significantly associated with response. Pairwise combinations of copy number status of these loci and ERBB2 amplicon size provided stronger associations and identified a group of patients without responders. These results suggest that patient selection for trastuzumab may be improved by considering ERBB2 amplicon size and genomic status of the 1q25, PTGS2, and centromere 10 loci.

  9. The role of ERBB2 gene polymorphisms in leprosy susceptibility

    Directory of Open Access Journals (Sweden)

    Jamile Leão Rêgo

    2015-04-01

    Full Text Available Mycobacterium lepraeinfects skin and peripheral nerves causing deformities and disability. The M. lepraebacterium binds to ErbB2 on the Schwann cell surface causing demyelination and favoring spread of the bacilli and causing nerve injury. Polymorphisms at the ERBB2 gene were previously investigated as genetic risk factors for leprosy in two Brazilian populations but with inconsistent results. Herein we extend the analysis of ERBB2 variants to a third geographically distinct population in Brazil. Our results show that there is no association between the genotyped SNPs and the disease (p> 0.05 in this population. A gene set or pathway analysis under the genomic region of ERBB2 will be necessary to clarify its regulation under M. lepraestimulus.

  10. The scaffold protein p140Cap limits ERBB2-mediated breast cancer progression interfering with Rac GTPase-controlled circuitries

    Science.gov (United States)

    Grasso, Silvia; Chapelle, Jennifer; Salemme, Vincenzo; Aramu, Simona; Russo, Isabella; Vitale, Nicoletta; Verdun di Cantogno, Ludovica; Dallaglio, Katiuscia; Castellano, Isabella; Amici, Augusto; Centonze, Giorgia; Sharma, Nanaocha; Lunardi, Serena; Cabodi, Sara; Cavallo, Federica; Lamolinara, Alessia; Stramucci, Lorenzo; Moiso, Enrico; Provero, Paolo; Albini, Adriana; Sapino, Anna; Staaf, Johan; Di Fiore, Pier Paolo; Bertalot, Giovanni; Pece, Salvatore; Tosoni, Daniela; Confalonieri, Stefano; Iezzi, Manuela; Di Stefano, Paola; Turco, Emilia; Defilippi, Paola

    2017-01-01

    The docking protein p140Cap negatively regulates tumour cell features. Its relevance on breast cancer patient survival, as well as its ability to counteract relevant cancer signalling pathways, are not fully understood. Here we report that in patients with ERBB2-amplified breast cancer, a p140Cap-positive status associates with a significantly lower probability of developing a distant event, and a clear difference in survival. p140Cap dampens ERBB2-positive tumour cell progression, impairing tumour onset and growth in the NeuT mouse model, and counteracting epithelial mesenchymal transition, resulting in decreased metastasis formation. One major mechanism is the ability of p140Cap to interfere with ERBB2-dependent activation of Rac GTPase-controlled circuitries. Our findings point to a specific role of p140Cap in curbing the aggressiveness of ERBB2-amplified breast cancers and suggest that, due to its ability to impinge on specific molecular pathways, p140Cap may represent a predictive biomarker of response to targeted anti-ERBB2 therapies. PMID:28300085

  11. K-RAS point mutation, and amplification of C-MYC and C-ERBB2 in colon adenocarcinoma.

    Directory of Open Access Journals (Sweden)

    Tadeusz Pawełczyk

    2004-10-01

    Full Text Available The routine multidisciplinary management of colon cancer is based mainly on tumor staging, histology, grading and vascular invasion. In this approach, important individual information derived from molecular characteristics of the tumor may be missed, especially since significant heterogeneity of molecular aberrations in cancer cells has been observed, and recognition of every of relationships between them may be of value. K-RAS, C-MYC and C-ERBB2 are protooncogenes taking part in carcinogenesis and tumor progression in the colon. They influence cell proliferation, differentiation and survival. K-RAS point mutation, as well as amplification of C-MYC and C-ERBB2 were searched in 84 primary colon adenocarcinomas resected with curative intent. Multiplex polymerase-chain reaction and restriction fragment length polymorphism were performed to assess codon 12 K-RAS point mutation. Amplification of C-MYC and C-ERBB2 genes was evaluated by densitometry after agarose gel separation of the respective multiplex PCR products. No relation was found among mutated and/or amplified genes, and between searched molecular aberrations and pathoclinical features. In multivariate analysis, nodal status appeared to be the only independent prognostic indicator. In colon adenocarcinoma, codon 12 K-RAS point mutation and amplification of C-MYC and C-ERBB2 seem to occur independently in the process of tumor progression. Amplification of C-ERBB2 tends to associate with more advanced stage of disease. Concomitant occurrence of codon 12 K-RAS mutation, C-MYC and C-ERBB2 amplification was of no prognostic value in respect to survival.

  12. Inhibition of ErbB-2 Mitogenic and Transforming Activity by RALT, a Mitogen-Induced Signal Transducer Which Binds to the ErbB-2 Kinase Domain†

    Science.gov (United States)

    Fiorentino, Loredana; Pertica, Chiara; Fiorini, Monia; Talora, Claudio; Crescenzi, Marco; Castellani, Loriana; Alemà, Stefano; Benedetti, Piero; Segatto, Oreste

    2000-01-01

    The product of rat gene 33 was identified as an ErbB-2-interacting protein in a two-hybrid screen employing the ErbB-2 juxtamembrane and kinase domains as bait. This interaction was reproduced in vitro with a glutathione S-transferase fusion protein spanning positions 282 to 395 of the 459-residue gene 33 protein. Activation of ErbB-2 catalytic function was required for ErbB-2–gene 33 physical interaction in living cells, whereas ErbB-2 autophosphorylation was dispensable. Expression of gene 33 protein was absent in growth-arrested NIH 3T3 fibroblasts but was induced within 60 to 90 min of serum stimulation or activation of the ErbB-2 kinase and decreased sharply upon entry into S phase. New differentiation factor stimulation of mitogen-deprived mammary epithelial cells also caused accumulation of gene 33 protein, which could be found in a complex with ErbB-2. Overexpression of gene 33 protein in mouse fibroblasts inhibited (i) cell proliferation driven by ErbB-2 but not by serum, (ii) cell transformation induced by ErbB-2 but not by Ras or Src, and (iii) sustained activation of ERK 1 and 2 by ErbB-2 but not by serum. The gene 33 protein may convey inhibitory signals downstream to ErbB-2 by virtue of its association with SH3-containing proteins, including GRB-2, which was found to associate with gene 33 protein in living cells. These data indicate that the gene 33 protein is a feedback inhibitor of ErbB-2 mitogenic function and a suppressor of ErbB-2 oncogenic activity. We propose that the gene 33 protein be renamed with the acronym RALT (receptor-associated late transducer). PMID:11003669

  13. Inhibition of ErbB-2 mitogenic and transforming activity by RALT, a mitogen-induced signal transducer which binds to the ErbB-2 kinase domain.

    Science.gov (United States)

    Fiorentino, L; Pertica, C; Fiorini, M; Talora, C; Crescenzi, M; Castellani, L; Alemà, S; Benedetti, P; Segatto, O

    2000-10-01

    The product of rat gene 33 was identified as an ErbB-2-interacting protein in a two-hybrid screen employing the ErbB-2 juxtamembrane and kinase domains as bait. This interaction was reproduced in vitro with a glutathione S-transferase fusion protein spanning positions 282 to 395 of the 459-residue gene 33 protein. Activation of ErbB-2 catalytic function was required for ErbB-2-gene 33 physical interaction in living cells, whereas ErbB-2 autophosphorylation was dispensable. Expression of gene 33 protein was absent in growth-arrested NIH 3T3 fibroblasts but was induced within 60 to 90 min of serum stimulation or activation of the ErbB-2 kinase and decreased sharply upon entry into S phase. New differentiation factor stimulation of mitogen-deprived mammary epithelial cells also caused accumulation of gene 33 protein, which could be found in a complex with ErbB-2. Overexpression of gene 33 protein in mouse fibroblasts inhibited (i) cell proliferation driven by ErbB-2 but not by serum, (ii) cell transformation induced by ErbB-2 but not by Ras or Src, and (iii) sustained activation of ERK 1 and 2 by ErbB-2 but not by serum. The gene 33 protein may convey inhibitory signals downstream to ErbB-2 by virtue of its association with SH3-containing proteins, including GRB-2, which was found to associate with gene 33 protein in living cells. These data indicate that the gene 33 protein is a feedback inhibitor of ErbB-2 mitogenic function and a suppressor of ErbB-2 oncogenic activity. We propose that the gene 33 protein be renamed with the acronym RALT (receptor-associated late transducer).

  14. Photo-activated psoralen binds the ErbB2 catalytic kinase domain, blocking ErbB2 signaling and triggering tumor cell apoptosis.

    Directory of Open Access Journals (Sweden)

    Wenle Xia

    Full Text Available Photo-activation of psoralen with UVA irradiation, referred to as PUVA, is used in the treatment of proliferative skin disorders. The anti-proliferative effects of PUVA have been largely attributed to psoralen intercalation of DNA, which upon UV treatment, triggers the formation of interstrand DNA crosslinks (ICL that inhibit transcription and DNA replication. Here, we show that PUVA exerts antitumor effects in models of human breast cancer that overexpress the ErbB2 receptor tyrosine kinase oncogene, through a new mechanism. Independent of ICL formation, the antitumor effects of PUVA in ErbB2+ breast cancer models can instead be mediated through inhibition of ErbB2 activation and signaling. Using a mass spectroscopy-based approach, we show for the first time that photo-activated 8MOP (8-methoxypsoralen interacts with the ErbB2 catalytic autokinase domain. Furthermore, PUVA can reverse therapeutic resistance to lapatinib and other ErbB2 targeted therapies, including resistance mediated via expression of a phosphorylated, truncated form of ErbB2 (p85(ErbB2 that is preferentially expressed in tumor cell nuclei. Current ErbB2 targeted therapies, small molecule kinase inhibitors or antibodies, do not block the phosphorylated, activated state of p85(ErbB2. Here we show that PUVA reduced p85(ErbB2 phosphorylation leading to tumor cell apoptosis. Thus, in addition to its effects on DNA and the formation of ICL, PUVA represents a novel ErbB2 targeted therapy for the treatment of ErbB2+ breast cancers, including those that have developed resistance to other ErbB2 targeted therapies.

  15. Inhibition of ERBB2-overexpressing Tumors by Recombinant Human Prolidase and Its Enzymatically Inactive Mutant

    Directory of Open Access Journals (Sweden)

    Lu Yang

    2015-05-01

    Full Text Available ERBB2 is an oncogenic receptor tyrosine kinase overexpressed in a subset of human breast cancer and other cancers. We recently found that human prolidase (PEPD, a dipeptidase, is a high affinity ERBB2 ligand and cross-links two ERBB2 monomers. Here, we show that recombinant human PEPD (rhPEPD strongly inhibits ERBB2-overexpressing tumors in mice, whereas it does not impact tumors without ERBB2 overexpression. rhPEPD causes ERBB2 depletion, disrupts oncogenic signaling orchestrated by ERBB2 homodimers and heterodimers, and induces apoptosis. The impact of enzymatically-inactive mutant rhPEPDG278D on ERBB2 is indistinguishable from that of rhPEPD, but rhPEPDG278D is superior to rhPEPD for tumor inhibition. The enzymatic function of rhPEPD stimulates HIF-1α and other pro-survival factors in tumors, which likely attenuates its antitumor activity. rhPEPDG278D is also attractive in that it may not interfere with the physiologic function of endogenous PEPD in normal cells. Collectively, we have identified a human protein as an inhibitory ERBB2 ligand that inhibits ERBB2-overexpressing tumors in vivo. Several anti-ERBB2 agents are on the market but are hampered by drug resistance and high drug cost. rhPEPDG278D may synergize with these agents and may also be highly cost-effective, since it targets ERBB2 with a different mechanism and can be produced in bacteria.

  16. ErbB2 signaling at the crossing between heart failure and cancer

    OpenAIRE

    Vermeulen, Zarha; Segers, Vincent F.M.; De Keulenaer, Gilles W.

    2016-01-01

    The dual role of ErbB2 (or HER-2) in tumor growth and in physiological adaptive reactions of the heart positions ErbB2 at the intersection between cancer and chronic heart failure. Accordingly, ErbB2-targeted inhibitory therapy of cancer may lead to ventricular dysfunction, and activation of ErbB2 for heart failure therapy may induce malignancy. The molecular processes leading to the activation of ErbB2 in tumors and cardiac cells are, however, fundamentally different from each other. Thus, i...

  17. Inhibition of ErbB-2 induces TFF3 downregulation in breast cancer cell lines.

    Science.gov (United States)

    Yue, Lu; Xiang, Jinyu; Shen, Zan; Wang, Zhihao; Yao, Yasai; Zhou, Quan; Ding, Aiping; Qiu, Wensheng

    2014-07-01

    ErbB-2 gene plays an important role in carcinoma formation whose overexpression was observed in many types of tumors, including breast cancer. Dysregulation of Trefoil factor 3 (TFF3), which is thought to function in the development and progression of breast cancer, was found to be upregulated in ErbB2-overexpressing breast cancers and cells. However, a putative interaction between ErbB-2 and TFF3 in breast cancer remains unknown. To determine whether TFF3 has an important role in breast tumor, its levels were measured by immunohistochemistry in 130 cases of breast infiltrating duct carcinoma and 30 cases of normal breast tissue with a specific monoclonal antibody raised against human TFF3. Patients who were positive for ErbB-2 also had high expression levels of TFF3 (p TFF3 by real-time polymerase chain reaction and Western blotting, respectively. Compared with the control groups, ErbB-2 mRNA expression was decreased in the Lenti-ShERBB2 infection group, and Western blotting indicated a concordant ErbB-2 protein reduction. On the other hand, TFF3 expression at both mRNA and protein levels was significantly downregulated by ErbB-2 silencing in SK-BR-3. These findings are a proof of the foundation for a certain relationships of ErbB-2 and TFF3, which may serve as novel therapeutic markers of ErbB2-overexpressing breast cancers in the future.

  18. Preubiquitinated chimeric ErbB2 is constitutively endocytosed and subsequently degraded in lysosomes

    Energy Technology Data Exchange (ETDEWEB)

    Vuong, Tram Thu [Institute of Clinical Medicine, University of Oslo, Rikshospitalet, 0027 Oslo (Norway); Berger, Christian [Department of Pathology, Oslo University Hospital, Rikshospitalet, P.O. Box 4950 Nydalen, 0424 Oslo (Norway); Bertelsen, Vibeke; Rødland, Marianne Skeie [Institute of Clinical Medicine, University of Oslo, Rikshospitalet, 0027 Oslo (Norway); Stang, Espen [Department of Pathology, Oslo University Hospital, Rikshospitalet, P.O. Box 4950 Nydalen, 0424 Oslo (Norway); Madshus, Inger Helene, E-mail: i.h.madshus@medisin.uio.no [Institute of Clinical Medicine, University of Oslo, Rikshospitalet, 0027 Oslo (Norway); Department of Pathology, Oslo University Hospital, Rikshospitalet, P.O. Box 4950 Nydalen, 0424 Oslo (Norway)

    2013-02-01

    The oncoprotein ErbB2 is endocytosis-deficient, probably due to its interaction with Heat shock protein 90. We previously demonstrated that clathrin-dependent endocytosis of ErbB2 is induced upon incubation of cells with Ansamycin derivatives, such as geldanamycin and its derivative 17-AAG. Furthermore, we have previously demonstrated that a preubiquitinated chimeric EGFR (EGFR-Ub{sub 4}) is constitutively endocytosed in a clathrin-dependent manner. We now demonstrate that also an ErbB2-Ub{sub 4} chimera is endocytosed constitutively and clathrin-dependently. Upon expression, the ErbB2-Ub{sub 4} was further ubiquitinated, and by Western blotting, we demonstrated the formation of both Lys48-linked and Lys63-linked polyubiquitin chains. ErbB2-Ub{sub 4} was constitutively internalized and eventually sorted to late endosomes and lysosomes where the fusion protein was degraded. ErbB2-Ub{sub 4} was not cleaved prior to internalization. Interestingly, over-expression of Ubiquitin Interaction Motif-containing dominant negative fragments of the clathrin adaptor proteins epsin1 and Eps15 negatively affected endocytosis of ErbB2. Altogether, this argues that ubiquitination is sufficient to induce clathrin-mediated endocytosis and lysosomal degradation of the otherwise plasma membrane localized ErbB2. Also, it appears that C-terminal cleavage is not required for endocytosis. -- Highlights: ► A chimera containing ErbB2 and a tetra-Ubiquitin chain internalizes constitutively. ► Receptor fragmentation is not required for endocytosis of ErbB2. ► Ubiquitination is sufficient to induce endocytosis and degradation of ErbB2. ► ErbB2-Ub4 is internalized clathrin-dependently.

  19. erbB2 is required for G protein-coupled receptor signaling in the heart

    OpenAIRE

    Negro, Alejandra; Brar, Bhawanjit K.; Gu, Yusu; Peterson, Kirk L.; Vale, Wylie; Lee, Kuo-Fen

    2006-01-01

    erbB2/Her2, a ligandless receptor kinase, has pleiotropic effects on mammalian development and human disease. The absence of erbB2 signaling in cardiac myocytes results in dilated cardiomyopathy in mice, resembling the cardiotoxic effects observed in a subset of breast cancer patients treated with the anti-Her2 antibody herceptin. Emerging evidence suggests that erbB2 is pivotal for integrating signaling networks involving multiple classes of extracellular signals. However, its role in G prot...

  20. Role of Erbin in ErbB2-dependent breast tumor growth.

    Science.gov (United States)

    Tao, Yanmei; Shen, Chengyong; Luo, Shiwen; Traoré, Wilfried; Marchetto, Sylvie; Santoni, Marie-Josée; Xu, Linlin; Wu, Biao; Shi, Chao; Mei, Jinghong; Bates, Ryan; Liu, Xihui; Zhao, Kai; Xiong, Wen-Cheng; Borg, Jean-Paul; Mei, Lin

    2014-10-21

    ErbB2 (v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 2), a receptor tyrosine kinase of the ErbB family, is overexpressed in around 25% of breast cancers. In addition to forming a heterodimer with other ErbB receptors in response to ligand stimulation, ErbB2 can be activated in a ligand-independent manner. We report here that Erbin, an ErbB2-interacting protein that was thought to act as an antitumor factor, is specifically expressed in mammary luminal epithelial cells and facilitates ErbB2-dependent proliferation of breast cancer cells and tumorigenesis in MMTV-neu transgenic mice. Disruption of their interaction decreases ErbB2-dependent proliferation, and deletion of the PDZ domain in Erbin hinders ErbB2-dependent tumor development in MMTV-neu mice. Mechanistically, Erbin forms a complex with ErbB2, promotes its interaction with the chaperon protein HSP90, and thus prevents its degradation. Finally, ErbB2 and Erbin expression correlates in human breast tumor tissues. Together, these observations establish Erbin as an ErbB2 regulator for breast tumor formation and progression.

  1. Src mutation induces acquired lapatinib resistance in ERBB2-amplified human gastroesophageal adenocarcinoma models.

    Directory of Open Access Journals (Sweden)

    Yong Sang Hong

    Full Text Available ERBB2-directed therapy is now a routine component of therapy for ERBB2-amplified metastatic gastroesophageal adenocarcinomas. However, there is little knowledge of the mechanisms by which these tumors develop acquired resistance to ERBB2 inhibition. To investigate this question we sought to characterize cell line models of ERBB2-amplified gastroesophageal adenocarcinoma with acquired resistance to ERBB2 inhibition. We generated lapatinib-resistant (LR subclones from an initially lapatinib-sensitive ERBB2-amplified esophageal adenocarcinoma cell line, OE19. We subsequently performed genomic characterization and functional analyses of resistant subclones with acquired lapatinib resistance. We identified a novel, acquired SrcE527K mutation in a subset of LR OE19 subclones. Cells with this mutant allele harbour increased Src phosphorylation. Genetic and pharmacologic inhibition of Src resensitized these subclones to lapatinib. Biochemically, Src mutations could activate both the phosphatidylinositol 3-kinase and mitogen activated protein kinase pathways in the lapatinib-treated LR OE19 cells. Ectopic expression of SrcE527K mutation also was sufficient to induce lapatinib resistance in drug-naïve cells. These results indicate that pathologic activation of Src is a potential mechanism of acquired resistance to ERBB2 inhibition in ERBB2-amplified gastroesophageal cancer. Although Src mutation has not been described in primary tumor samples, we propose that the Src hyperactivation should be investigated in the settings of acquired resistance to ERBB2 inhibition in esophageal and gastric adenocarcinoma.

  2. LINGO-1 regulates oligodendrocyte differentiation by inhibiting ErbB2 translocation and activation in lipid rafts.

    Science.gov (United States)

    Lee, Xinhua; Shao, Zhaohui; Sheng, Guoqing; Pepinsky, Blake; Mi, Sha

    2014-05-01

    Oligodendrocyte differentiation is negatively regulated by LINGO-1 and positively regulated by the ErbB2 receptor tyrosine kinase. In wild-type oligodendrocytes, inhibition of ErbB2 blocks differentiation, whereas activation of ErbB2 promotes differentiation. In LINGO-1(-/-) oligodendrocytes, inhibition of ErbB2 blocks oligodendrocyte differentiation; whereas activation of ErbB2 does not enhance differentiation. Biological and biochemical evidence showing that LINGO-1 can directly bind to ErbB2, block ErbB2 translocation into lipid rafts, and inhibit its phosphorylation for activation. The study demonstrates a novel regulatory mechanism of ErbB2 function whereby LINGO-1 suppresses oligodendrocyte differentiation by inhibiting ErbB2 translocation and activation in lipid rafts.

  3. ERBB2 in cat mammary neoplasias disclosed a positive correlation between RNA and protein low expression levels: a model for erbB-2 negative human breast cancer.

    Directory of Open Access Journals (Sweden)

    Sara Santos

    Full Text Available Human ERBB2 is a proto-oncogene that codes for the erbB-2 epithelial growth factor receptor. In human breast cancer (HBC, erbB-2 protein overexpression has been repeatedly correlated with poor prognosis. In more recent works, underexpression of this gene has been described in HBC. Moreover, it is also recognised that oncogenes that are commonly amplified or deleted encompass point mutations, and some of these are associated with HBC. In cat mammary lesions (CMLs, the overexpression of ERBB2 (27%-59.6% has also been described, mostly at the protein level and although cat mammary neoplasias are considered to be a natural model of HBC, molecular information is still scarce. In the present work, a cat ERBB2 fragment, comprising exons 10 to 15 (ERBB2_10-15 was achieved for the first time. Allelic variants and genomic haplotype analyses were also performed, and differences between normal and CML populations were observed. Three amino acid changes, corresponding to 3 non-synonymous genomic sequence variants that were only detected in CMLs, were proposed to damage the 3D structure of the protein. We analysed the cat ERBB2 gene at the DNA (copy number determination, mRNA (expression levels assessment and protein levels (in extra- and intra protein domains in CML samples and correlated the last two evaluations with clinicopathological features. We found a positive correlation between the expression levels of the ERBB2 RNA and erbB-2 protein, corresponding to the intracellular region. Additionally, we detected a positive correlation between higher mRNA expression and better clinical outcome. Our results suggest that the ERBB2 gene is post-transcriptionally regulated and that proteins with truncations and single point mutations are present in cat mammary neoplastic lesions. We would like to emphasise that the recurrent occurrence of low erbB-2 expression levels in cat mammary tumours, suggests the cat mammary neoplasias as a valuable model for erbB-2

  4. Aberrations of ERBB2 and TOP2A Genes in Breast Cancer

    DEFF Research Database (Denmark)

    Nielsen, Kirsten Vang; Müller, Sven; Møller, Susanne;

    2009-01-01

    Copy number changes in TOP2A have frequently been linked to ERBB2 (HER2) amplified breast cancers. To study this relationship, copy number changes of ERBB2 and TOP2A were investigated by fluorescence in situ hybridization (FISH) in two cell lines; one characterized by having amplification of both...... genes and the other by having amplification of ERBB2 and deletion of TOP2A. The characteristics are compared to findings on paired ERBB2 and TOP2A data from 649 patients with invasive breast cancer from a previously published biomarker study. The physical localization of FISH signals in metaphase...... compared to TOP2A. In the majority of breast cancer patients, simultaneous aberration of ERBB2 and TOP2A is not explained by simple co-amplification....

  5. TPD52 represents a survival factor in ERBB2-amplified breast cancer cells.

    Science.gov (United States)

    Roslan, Nuruliza; Bièche, Ivan; Bright, Robert K; Lidereau, Rosette; Chen, Yuyan; Byrne, Jennifer A

    2014-10-01

    TPD52 and ERBB2 co-expression has been persistently reported in human breast cancer and animal models of this disease, but the significance of this is unknown. We identified significant positive associations between relative TPD52 and ERBB2 transcript levels in human diagnostic breast cancer samples, and maximal TPD52 expression in the hormone receptor (HR)- and ERBB2-positive sub-group. High-level TPD52 expression was associated with significantly reduced metastasis-free survival, within the overall cohort (log rank test, P = 8.6 × 10(-4), n = 375) where this was an independent predictor of metastasis-free survival (hazard ratio, 2.69, 95% confidence interval 1.59-4.54, P = 2.2 × 10(-4), n = 359), and the HR- and ERBB2-positive sub-group (log rank test, P = 0.035, n = 47). Transient TPD52 knock-down in the ERBB2-amplified breast cancer cell lines SK-BR-3 and BT-474 produced significant apoptosis, both singly and in combination with transient ERBB2 knock-down. Unlike ERBB2 knock-down, transient TPD52 knock-down produced no reduction in pAKT levels in SK-BR-3 or BT-474 cells. We then derived multiple SK-BR-3 cell lines in which TPD52 levels were stably reduced, and measured significant inverse correlations between pERBB2 and TPD52 levels in viable TPD52-depleted and control cell lines, all of which showed similar proliferative capacities. Our results therefore identify TPD52 as a survival factor in ERBB2-amplified breast cancer cells, and suggest complementary cellular functions for TPD52 and ERBB2.

  6. ErbB2 resembles an autoinhibited invertebrate epidermal growth factor receptor

    Energy Technology Data Exchange (ETDEWEB)

    Alvarado, Diego; Klein, Daryl E.; Lemmon, Mark A.; (UPENN-MED)

    2009-09-25

    The orphan receptor tyrosine kinase ErbB2 (also known as HER2 or Neu) transforms cells when overexpressed, and it is an important therapeutic target in human cancer. Structural studies have suggested that the oncogenic (and ligand-independent) signalling properties of ErbB2 result from the absence of a key intramolecular 'tether' in the extracellular region that autoinhibits other human ErbB receptors, including the epidermal growth factor (EGF) receptor. Although ErbB2 is unique among the four human ErbB receptors, here we show that it is the closest structural relative of the single EGF receptor family member in Drosophila melanogaster (dEGFR). Genetic and biochemical data show that dEGFR is tightly regulated by growth factor ligands, yet a crystal structure shows that it, too, lacks the intramolecular tether seen in human EGFR, ErbB3 and ErbB4. Instead, a distinct set of autoinhibitory interdomain interactions hold unliganded dEGFR in an inactive state. All of these interactions are maintained (and even extended) in ErbB2, arguing against the suggestion that ErbB2 lacks autoinhibition. We therefore suggest that normal and pathogenic ErbB2 signalling may be regulated by ligands in the same way as dEGFR. Our findings have important implications for ErbB2 regulation in human cancer, and for developing therapeutic approaches that target novel aspects of this orphan receptor.

  7. Identification of novel nuclear localization signal within the ErbB-2 protein

    Institute of Scientific and Technical Information of China (English)

    Qiao Qiao CHEN; Xiao Ying CHEN; Yun Yun JIANG; Jing LIU

    2005-01-01

    ErbB2,a member of the receptor tyrosine kinase family,is frequently over-expressed in breast cancer.Proteolysis of the extracellular domain of ErbB2 results in constitutive activation of ErbB2 kinase.Recent study reported that ErbB2 is found in the nucleus.Here,we showed that ErbB2 is imported into the nucleus through a nuclear localization signal (NLS)-mediated mechanism.The NLS sequence KRRQQKIRKYTMRR (aa655-668) contains three clusters of basic amino acids and it is sufficient to target GFP into the nucleus.However,mutation in any basic amino acid cluster of this NLS sequence significantly affects its nuclear localization.Furthermore,it was found that this NLS is essential for the nuclear localization of ErbB2 since the intracellular domain of Erb2 lacking NLS completely abrogates its nuclear translocation.Taken together,our study identified a novel nuclear localization signal and reveals a novel mechanism underlying ErbB2 nuclear trafficking and localization.

  8. FASN, ErbB2-mediated glycolysis is required for breast cancer cell migration.

    Science.gov (United States)

    Zhou, Lan; Jiang, Sufang; Fu, Qiang; Smith, Kelly; Tu, Kailing; Li, Hua; Zhao, Yuhua

    2016-05-01

    Both fatty acid synthase (FASN) and ErbB2 have been shown to promote breast cancer cell migration. However, the underlying molecular mechanism remains poorly understood and there is no reported evidence that directly links glycolysis to breast cancer cell migration. In this study, we investigated the role of FASN, ErbB2-mediated glycolysis in breast cancer cell migration. First, we compared lactate dehydrogenase A (LDHA) protein levels, glycolysis and cell migration between FASN, ErbB2-overexpressing SK-BR-3 cells and FASN, ErbB2-low-expressing MCF7 cells. Then, SK-BR-3 cells were treated with cerulenin (Cer), an inhibitor of FASN, and ErbB2, LDHA protein levels, glycolysis, and cell migration were detected. Next, we transiently transfected ErbB2 plasmid into MCF7 cells and detected FASN, LDHA protein levels, glycolysis and cell migration. Heregulin-β1 (HRG-β1) is an activator of ErbB2 and 2-deoxyglucose (2-DG) and oxamate (OX) are inhibitors of glycolysis. MCF7 cells were treated with HRG-β1 alone, HRG-β1 plus 2-DG, OX or cerulenin and glycolysis, and cell migration were measured. We found that FASN, ErbB2-high-expressing SK-BR-3 cells displayed higher levels of glycolysis and migration than FASN, ErbB2-low-expressing MCF7 cells. Inhibition of FASN by cerulenin impaired glycolysis and migration in SK-BR-3 cells. Transient overexpression of ErbB2 in MCF7 cells promotes glycolysis and migration. Moreover, 2-deoxyglucose (2-DG), oxamate (OX), or cerulenin partially reverses heregulin-β1 (HRG-β1)-induced glycolysis and migration in MCF7 cells. In conclusion, this study demonstrates that FASN, ErbB2-mediated glycolysis is required for breast cancer cell migration. These novel findings indicate that targeting FASN, ErbB2-mediated glycolysis may be a new approach to reverse breast cancer cell migration.

  9. Effect of c- erbB2 Antisense Oligodeoxynucleotides on Radiosensitivity of Human Ovarian Cancer Cell Line

    Institute of Scientific and Technical Information of China (English)

    RENQing-Lan

    2003-01-01

    Object To explore tile effect of lipofectin - c - erbB2 antisense oligodeoxynucleotides on radiosensitivity of human ovarian cancer cell llne. Methods The expression of c - erbB2 was detected by means of RT - PCR, cellular response to irradiation was evaluated by tile colony forming assay. Results Lipofectin- c - erbB2 antisense oligodeoxynucleotides(AS- ODN) could suppress the expression of c - erbB2 , and significantly decreased the colony forming rate of human ovarian cancer cells after ionizing irradiation (P 0.05 ). Condusion c - erbB2 antisense oligodeoxynueleotides sensitized the SKOV3 to ionizing irradiation through decreasing the expression of e - erbB2 , which might be the result of the fact that c - erbB2 antisense oligodeoxynueleotides inhibit the eelluar signal transductionpathway relating to the radiation- resistant phenotype.

  10. ERBB2 increases metastatic potentials specifically in androgen-insensitive prostate cancer cells.

    Directory of Open Access Journals (Sweden)

    Jessica Tome-Garcia

    Full Text Available Despite all the blood-based biomarkers used to monitor prostate cancer patients, prostate cancer remains as the second common cause of cancer mortality in men in the United States. This is largely due to a lack of understanding of the molecular pathways that are responsible for the aggressive forms of prostate cancers, the castrate-resistant prostate cancer and the metastatic prostate cancer. Cell signaling pathways activated by the ERBB2 oncogene or the RAS oncogene are frequently found to be altered in metastatic prostate cancers. To evaluate and define the role of the ERBB2/RAS pathway in prostate cancer metastasis, we have evaluated the impact of ERBB2- or RAS-overexpression on the metastatic potentials for four prostate cancer cell lines derived from tumors with different androgen sensitivities. To do so, we transfected the human DU145, LnCaP, and PC3 prostate cancer cells and the murine Myc-CaP prostate cancer cells with the activated form of ERBB2 or H-RAS and assessed their metastatic potentials by three complementary assays, a wound healing assay, a transwell motility assay, and a transwell invasion assay. We showed that while overexpression of ERBB2 increased the metastatic potential of the androgen-insensitive prostate cancer cells (i.e. PC3 and DU145, it did not affect metastatic potentials of the androgen-sensitive prostate cancer cells (i.e. LnCaP and Myc-CaP. In contrast, overexpression of H-RAS only increased the cell motility of Myc-CaP cells, which overexpress the human c-MYC oncogene. Our data suggest that ERBB2 collaborates with androgen signaling to promote prostate cancer metastasis, and that although RAS is one of the critical downstream effectors of ERBB2, it does not phenocopy ERBB2 for its impact on the metastatic potentials of prostate cancer cell lines.

  11. Chimeric DNA Vaccines against ErbB2{sup +} Carcinomas: From Mice to Humans

    Energy Technology Data Exchange (ETDEWEB)

    Quaglino, Elena; Riccardo, Federica; Macagno, Marco; Bandini, Silvio; Cojoca, Rodica; Ercole, Elisabetta [Molecular Biotechnology Center, Department of Clinical and Biological Sciences, University of Turin, 10126 Turin (Italy); Amici, Augusto [Department of Molecular Cellular and Animal Biology, University of Camerino, 62032 Camerino (Italy); Cavallo, Federica, E-mail: federica.cavallo@unito.it [2 Department of Molecular Cellular and Animal Biology, University of Camerino, 62032 Camerino (Italy)

    2011-08-10

    DNA vaccination exploits a relatively simple and flexible technique to generate an immune response against microbial and tumor-associated antigens (TAAs). Its effectiveness is enhanced by the application of an electrical shock in the area of plasmid injection (electroporation). In our studies we exploited a sophisticated electroporation device approved for clinical use (Cliniporator, IGEA, Carpi, Italy). As the target antigen is an additional factor that dramatically modulates the efficacy of a vaccine, we selected ErbB2 receptor as a target since it is an ideal oncoantigen. It is overexpressed on the cell membrane by several carcinomas for which it plays an essential role in driving their progression. Most oncoantigens are self-tolerated molecules. To circumvent immune tolerance we generated two plasmids (RHuT and HuRT) coding for chimeric rat/human ErbB2 proteins. Their immunogenicity was compared in wild type mice naturally tolerant for mouse ErbB2, and in transgenic mice that are also tolerant for rat or human ErbB2. In several of these mice, RHuT and HuRT elicited a stronger anti-tumor response than plasmids coding for fully human or fully rat ErbB2. The ability of heterologous moiety to blunt immune tolerance could be exploited to elicit a significant immune response in patients. A clinical trial to delay the recurrence of ErbB2{sup +} carcinomas of the oral cavity, oropharynx and hypopharynx is awaiting the approval of the Italian authorities.

  12. Flotillins as regulators of ErbB2 levels in breast cancer

    DEFF Research Database (Denmark)

    Pust, S; Klokk, T I; Musa, N;

    2013-01-01

    Amplification and overexpression of the receptor tyrosine kinase ErbB2 occur in up to 30% of human breast cancers, and high ErbB2 levels are correlated with poor prognosis for breast cancer patients. In contrast to the epithelial growth factor receptor (ErbB1), ErbB2 is not downregulated by ligand...... from 194 patients diagnosed with carcinomas of the breast showed that flotillin-2 emerged as a potential predictor of prognosis in breast cancer. Depletion of flotillin-1 and flotillin-2 leads to internalization and degradation of ErbB2. Furthermore, flotillin-1 and -2 were found to be in a molecular......-induced mechanisms. Here we show that flotillins are involved in the stabilization of ErbB2 at the plasma membrane. In SKBR3 breast cancer cells and breast cancer tissue, a positive correlation between flotillin and ErbB2 expression levels could be demonstrated. Moreover, the tissue microarray analyses of biopsies...

  13. Regulation of ErbB2 localization and function in breast cancer cells by ERM proteins

    Science.gov (United States)

    Asp, Nagham; Kvalvaag, Audun; Sandvig, Kirsten; Pust, Sascha

    2016-01-01

    The ERM protein family is implicated in processes such as signal transduction, protein trafficking, cell proliferation and migration. Consequently, dysregulation of ERM proteins has been described to correlate with carcinogenesis of different cancer types. However, the underlying mechanisms are poorly understood. Here, we demonstrate a novel functional interaction between ERM proteins and the ErbB2 receptor tyrosine kinase in breast cancer cells. We show that the ERM proteins ezrin and radixin are associated with ErbB2 receptors at the plasma membrane, and depletion or functional inhibition of ERM proteins destabilizes the interaction of ErbB2 with ErbB3, Hsp90 and Ebp50. Accompanied by the dissociation of this protein complex, binding of ErbB2 to the ubiquitin-ligase c-Cbl is increased, and ErbB2 becomes dephosphorylated, ubiquitinated and internalized. Furthermore, signaling via Akt- and Erk-mediated pathways is impaired upon ERM inhibition. Finally, interference with ERM functionality leads to receptor degradation and reduced cellular levels of ErbB2 and ErbB3 receptors in breast cancer cells. PMID:27029001

  14. ErbB2-dependent chemotaxis requires microtubule capture and stabilization coordinated by distinct signaling pathways.

    Directory of Open Access Journals (Sweden)

    Khedidja Benseddik

    Full Text Available Activation of the ErbB2 receptor tyrosine kinase stimulates breast cancer cell migration. Cell migration is a complex process that requires the synchronized reorganization of numerous subcellular structures including cell-to-matrix adhesions, the actin cytoskeleton and microtubules. How the multiple signaling pathways triggered by ErbB2 coordinate, in time and space, the various processes involved in cell motility, is poorly defined. We investigated the mechanism whereby ErbB2 controls microtubules and chemotaxis. We report that activation of ErbB2 increased both cell velocity and directed migration. Impairment of the Cdc42 and RhoA GTPases, but not of Rac1, prevented the chemotactic response. RhoA is a key component of the Memo/ACF7 pathway whereby ErbB2 controls microtubule capture at the leading edge. Upon Memo or ACF7 depletion, microtubules failed to reach the leading edge and cells lost their ability to follow the chemotactic gradient. Constitutive ACF7 targeting to the membrane in Memo-depleted cells reestablished directed migration. ErbB2-mediated activation of phospholipase C gamma (PLCγ also contributed to cell guidance. We further showed that PLCγ signaling, via classical protein kinases C, and Memo signaling converged towards a single pathway controlling the microtubule capture complex. Finally, inhibiting the PI3K/Akt pathway did not affect microtubule capture, but disturbed microtubule stability, which also resulted in defective chemotaxis. PI3K/Akt-dependent stabilization of microtubules involved repression of GSK3 activity on the one hand and inhibition of the microtubule destabilizing protein, Stathmin, on the other hand. Thus, ErbB2 triggers distinct and complementary pathways that tightly coordinate microtubule capture and microtubule stability to control chemotaxis.

  15. RhNRG-1β Protects the Myocardium against Irradiation-Induced Damage via the ErbB2-ERK-SIRT1 Signaling Pathway.

    Directory of Open Access Journals (Sweden)

    Anxin Gu

    Full Text Available Radiation-induced heart disease (RIHD, which is a serious side effect of the radiotherapy applied for various tumors due to the inevitable irradiation of the heart, cannot be treated effectively using current clinical therapies. Here, we demonstrated that rhNRG-1β, an epidermal growth factor (EGF-like protein, protects myocardium tissue against irradiation-induced damage and preserves cardiac function. rhNRG-1β effectively ameliorated irradiation-induced myocardial nuclear damage in both cultured adult rat-derived cardiomyocytes and rat myocardium tissue via NRG/ErbB2 signaling. By activating ErbB2, rhNRG-1β maintained mitochondrial integrity, ATP production, respiratory chain function and the Krebs cycle status in irradiated cardiomyocytes. Moreover, the protection of irradiated cardiomyocytes and myocardium tissue by rhNRG-1β was at least partly mediated by the activation of the ErbB2-ERK-SIRT1 signaling pathway. Long-term observations further showed that rhNRG-1β administered in the peri-irradiation period exerts continuous protective effects on cardiac pump function, the myocardial energy metabolism, cardiomyocyte volume and interstitial fibrosis in the rats receiving radiation via NRG/ErbB2 signaling. Our findings indicate that rhNRG-1β can protect the myocardium against irradiation-induced damage and preserve cardiac function via the ErbB2-ERK-SIRT1 signaling pathway.

  16. Activating Mutations in ERBB2 and Their Impact on Diagnostics and Treatment

    Science.gov (United States)

    Herter-Sprie, Grit S.; Greulich, Heidi; Wong, Kwok-Kin

    2013-01-01

    Despite the ongoing “war on cancer,” cancer remains one of the major causes of human morbidity and mortality. A new paradigm of targeted therapies holds the most promise for the future, making identification of tumor-specific therapeutic targets of prime importance. ERBB2/HER2, best known for its role in breast cancer tumorigenesis, can be targeted by two types of pharmacological manipulation: antibody therapy against the extracellular receptor domain and small molecule compounds against the intracellular tyrosine kinase domain. Aberrant activation of ERBB2 by gene amplification has been shown to participate in the pathophysiology of breast, ovarian, gastric, colorectal, lung, brain, and head and neck tumors. However, the advent of next-generation sequencing technologies has enabled efficient identification of activating molecular alterations of ERBB2. In this review, we will focus on the functional role of these somatic mutations that cause ERBB2 receptor activation. We will additionally discuss the current preclinical and clinical therapeutic strategies for targeting mutationally activated ERBB2. PMID:23630663

  17. ErbB2 and bone sialoprotein as markers for metastatic osteosarcoma cells

    Science.gov (United States)

    Valabrega, G; Fagioli, F; Corso, S; Madon, E; Brach del Prever, A; Biasin, E; Linari, A; Aglietta, M; Giordano, S

    2003-01-01

    Osteosarcoma is the most common malignant bone neoplasia occurring in young patients in the first two decades of life, and represents 20% of all primitive malignant bone tumours. At present, treatment of metastatic osteosarcoma is unsatisfactory. High-dose chemotherapy followed by CD34+ leukapheresis rescue may improve these poor results. Neoplastic cells contaminating the apheresis may, however, contribute to relapse. To identify markers suitable for detecting osteosarcoma cells in aphereses we analysed the expression of bone-specific genes (Bone Sialoprotein (BSP) and Osteocalcin) and oncogenes (Met and ErbB2) in 22 patients with metastatic osteosarcoma and six healthy stem cell donors. The expression of these genes in aphereses of patients affected by metastatic osteosarcoma was assessed by RT–PCR and Southern blot analysis. Met and Osteocalcin proved to be not useful markers since they are positive in aphereses of both patients with metastatic osteosarcoma and healthy stem cell donors. On the contrary, BSP was expressed at significant levels in 85% of patients. Moreover, 18% of patients showed a strong and significantly positive (seven to 16 times higher than healthy stem cell donors) ErbB2 expression. In all positive cases, neoplastic tissue also expressed ErbB2. Our data show that ErbB2 can be a useful marker for tumour contamination in aphereses of patients affected by ErbB2-expressing osteosarcomas and that analysis of Bone Sialoprotein expression can be an alternative useful marker. PMID:12569382

  18. Activating mutations in ERBB2 and their impact on diagnostics and treatment

    Directory of Open Access Journals (Sweden)

    Grit Sophie Herter-Sprie

    2013-04-01

    Full Text Available Despite the ongoing ‘war on cancer’, cancer remains one of the major causes of human morbidity and mortality. A new paradigm of targeted therapies holds the most promise for the future, making identification of tumor-specific therapeutic targets of prime importance. ERBB2, best known for its role in breast cancer tumorigenesis, can be targeted by two types of pharmacological manipulation: antibody therapy against the extracellular receptor domain and small molecule compounds against the intracellular tyrosine kinase domain. Aberrant activation of ERBB2 by gene amplification has been shown to participate in the pathophysiology of breast, ovarian, gastric, colorectal, lung, brain and head and neck tumors. However, the advent of next-generation sequencing technologies has enabled efficient identification of activating molecular alterations of ERBB2. In this review, we will focus on the functional role of these somatic mutations that cause ERBB2 receptor activation. We will additionally discuss the current preclinical and clinical therapeutic strategies for targeting mutationally activated ERBB2.

  19. The ErbB2 inhibitor Herceptin (Trastuzumab) promotes axonal outgrowth four weeks after acute nerve transection and repair.

    Science.gov (United States)

    Placheta, Eva; Hendry, J Michael; Wood, Matthew D; Lafontaine, Christine W; Liu, Edward H; Cecilia Alvarez Veronesi, M; Frey, Manfred; Gordon, Tessa; Borschel, Gregory H

    2014-10-17

    Accumulating evidence suggests that neuregulin, a potent Schwann cell mitogen, and its receptor, ErbB2, have an important role in regulating peripheral nerve regeneration. We hypothesized that Herceptin (Trastuzumab), a monoclonal antibody that binds ErbB2, would disrupt ErbB2 signaling, allowing us to evaluate ErbB2's importance in peripheral nerve regeneration. In this study, the extent of peripheral motor and sensory nerve regeneration and distal axonal outgrowth was analyzed two and four weeks after common peroneal (CP) nerve injury in rats. Outcomes analyzed included neuron counts after retrograde labeling, histomorphometry, and protein analysis. The data analysis revealed that there was no impact of Herceptin administration on either the numbers of motor or sensory neurons that regenerated their axons but histomorphometry revealed that Herceptin significantly increased the number of regenerated axons in the distal repaired nerve after 4 weeks. Protein analysis with Western blotting revealed no difference in either expression levels of ErbB2 or the amount of activated, phosphorylated ErbB2 in injured nerves. In conclusion, administration of the ErbB2 receptor inhibitor after nerve transection and surgical repair did not alter the number of regenerating neurons but markedly increased the number of regenerated axons per neuron in the distal nerve stump. Enhanced axon outgrowth in the presence of this ErbB2 inhibitor indicates that ErbB2 signaling may limit the numbers of axons that are emitted from each regenerating neuron.

  20. Transmembrane Domain Targeting Peptide Antagonizing ErbB2/Neu Inhibits Breast Tumor Growth and Metastasis

    Directory of Open Access Journals (Sweden)

    Alexia Arpel

    2014-09-01

    Full Text Available Breast cancer is still a deadly disease despite major achievements in targeted therapies designed to block ligands or ligand-binding subunits of major tyrosine kinase receptors. Relapse is significant and metastases deleterious, which demands novel strategies for fighting this disease. Here, we report a proof-of-concept experiment demonstrating that small peptides interfering with the transmembrane domain of the tyrosine kinase epidermal growth factor receptor ErbB2 exhibit anticancer properties when used at micromolar dosages in a genetically engineered mouse model of breast cancer. Different assays demonstrate the specificity of the ErbB2-targeting peptide, which induces long-term reduction of ErbB2 phosphorylation and Akt signaling consistent with reduced tumor cell proliferation and increased survival. Microcomputed tomography analysis established the antimetastatic activity of the peptide and its impact on primary tumor growth. This reveals the interior of the cell membrane as an unexplored dimension for drug design.

  1. Distinct ErbB2 receptor populations differentially interact with beta1 integrin in breast cancer cell models

    Science.gov (United States)

    Toscani, Andrés Martín; Sampayo, Rocío G.; Barabas, Federico Martín; Fuentes, Federico; Simian, Marina

    2017-01-01

    ErbB2 is a member of the ErbB family of tyrosine kinase receptors that plays a major role in breast cancer progression. Located at the plasma membrane, ErbB2 forms large clusters in spite of the presence of growth factors. Beta1 integrin, membrane receptor of extracellular matrix proteins, regulates adhesion, migration and invasiveness of breast cancer cells. Physical interaction between beta1 integrin and ErbB2 has been suggested although published data are contradictory. The aim of the present work was to study the interaction between ErbB2 and beta1 integrin in different scenarios of expression and activation. We determined that beta1 integrin and ErbB2 colocalization is dependent on the expression level of both receptors exclusively in adherent cells. In suspension cells, lack of focal adhesions leave integrins free to diffuse on the plasma membrane and interact with ErbB2 even at low expression levels of both receptors. In adherent cells, high expression of beta1 integrin leaves unbound receptors outside focal complexes that diffuse within the plasma membrane and interact with ErbB2 membrane domains. Superresolution imaging showed the existence of two distinct populations of ErbB2: a major population located in large clusters and a minor population outside these structures. Upon ErbB2 overexpression, receptors outside large clusters can freely diffuse at the membrane and interact with integrins. These results reveal how expression levels of beta1 integrin and ErbB2 determine their frequency of colocalization and show that extracellular matrix proteins shape membrane clusters distribution, regulating ErbB2 and beta1 integrin activity in breast cancer cells. PMID:28306722

  2. erbB-2 autophosphorylation is required for mitogenic action and high-affinity substrate coupling

    DEFF Research Database (Denmark)

    Segatto, O; Lonardo, F; Helin, K;

    1992-01-01

    -mutated chimera. When expressed in NR6 cells, the EGFR/erbB-2 5P mutant was unable to deliver a sizeable mitogenic signal when activated by EGF at physiological levels. In intact cells, the 5P mutant was still able to stimulate phosphorylation of the gamma isozyme of phospholipase C (PLC-gamma), a prototype erb......B-2 substrate, although with a delayed time course, indicating that the 5P mutation decreased the affinity of the erbB-2 kinase for this substrate. This conclusion was further supported by the inability of the 5P mutant to associate with PLC-gamma in co-immunoprecipitation experiments. We infer...

  3. Continuous requirement of ErbB2 kinase activity for loss of cell polarity and lumen formation in a novel ErbB2/Neu-driven murine cell line model of metastatic breast cancer

    Directory of Open Access Journals (Sweden)

    Cesar F Ortega-Cava

    2011-01-01

    Full Text Available Background: Well over a quarter of human breast cancers are ErbB2-driven and constitute a distinct subtype with substantially poorer prognosis. Yet, there are substantial gaps in our understanding of how ErbB2 tyrosine kinase activity unleashes a coordinated program of cellular and extracellular alterations that culminate in aggressive breast cancers. Cellular models that exhibit ErbB2 kinase dependency and can induce metastatic breast cancer in immune competent hosts are likely to help bridge this gap. Materials and Methods: Here, we derived and characterized a cell line model obtained from a transgenic ErbB2/Neu-driven mouse mammary adenocarcinoma. Results: The MPPS1 cell line produces metastatic breast cancers when implanted in the mammary fat pads of immune-compromised as well as syngeneic immune-competent hosts. MPPS1 cells maintain high ErbB2 overexpression when propagated in DFCI-1 or related media, and their growth is ErbB2-dependent, as demonstrated by concentration-dependent inhibition of proliferation with the ErbB kinase inhibitor Lapatinib. When grown in 3-dimensional (3-D culture on Matrigel, MPPS1 cells predominantly form large irregular cystic and solid structures. Remarkably, low concentrations of Lapatinib led to a switch to regular acinar growth on Matrigel. Immunofluorescence staining of control vs. Lapatinib-treated acini for markers of epithelial polarity revealed that inhibition of ErbB2 signaling led to rapid resumption of normal mammary epithelium-like cell polarity. Conclusions: The strict dependence of the MPPS1 cell system on ErbB2 signals for proliferation and alterations in cell polarity should allow its use to dissect ErbB2 kinase-dependent signaling pathways that promote loss of cell polarity, a key component of the epithelial mesenchymal transition and aggressiveness of ErbB2-driven breast cancers.

  4. erbB2 Overexpression in Uterine Serous Cancer: A Molecular Target for Trastuzumab Therapy

    Directory of Open Access Journals (Sweden)

    Karim S. ElSahwi

    2011-01-01

    Full Text Available Endometrial cancer is the most common female genital tract malignancy in the United States. Type I endometrial cancer is usually diagnosed at an early stage, and has a good prognosis. Type II is very aggressive, and is responsible for most uterine cancer relapses and deaths. Uterine serous adenocarcinomas (USC constitute the majority of Type II variants. They have a higher propensity for lymph node and distant metastases. They are frequently aneuploid and associated with p53 mutations. erbB2 overexpression in USC has been described. The incidence, which is higher in African Americans, ranges from 18–80%. erbB2 overexpression was found to be associated with higher stage, chemoresistance, and worse survival. Trastuzumab a humanized mAb was approved by the FDA for treatment of breast cancers that overexpress erbB2 in combination with standard chemotherapy. Evidence of trastuzumab activity in USC has been reported in vitro, as well as in case reports of advanced and recurrent cases. Promising results were obtained in these heavily pretreated patients either with trastuzumab alone or in combination with chemotherapy. This supports the hypothesis that trastuzumab may very well be an attractive and viable treatment option for advanced stage USC tumors that overexpress the erbB2, and is worthy of further study.

  5. Development of Specific Inhibitors for Breast Cancer-Associated Variants of ErbB2

    Science.gov (United States)

    2015-10-01

    baculoviruses and used them to infect Sf9 cells in one-liter spinner flasks. We purified the proteins using metal affinity, ion exchange, and gel filtration...antibodies. Similar results were obtained in three separate experiments. Purification of wild-type ErbB2. Sf9 cells (600 ml) were infected with

  6. Enhanced internalization of ErbB2 in SK-BR-3 cells with multivalent forms of an artificial ligand.

    Science.gov (United States)

    Vaidyanath, Arun; Hashizume, Toshihiro; Nagaoka, Tadahiro; Takeyasu, Nao; Satoh, Hitomi; Chen, Ling; Wang, Jiyou; Kasai, Tomonari; Kudoh, Takayuki; Satoh, Ayano; Fu, Li; Seno, Masaharu

    2011-11-01

    Targeting and down-regulation of ErbB2, a member of EGF receptor family, is regarded as one of the key aspect for cancer treatment because it is often overexpressed in breast and ovarian cancer cells. Although natural ligands for ErbB2 have not been found, unlike other ErbB receptors, EC-1, a 20-amino acid circular peptide, has been shown to bind to ErbB2 as an artificial ligand. Previously we showed EC-1 peptide did not induce the internalization of ErbB2 in SK-BR-3 cells. In this report, we designed divalent and multivalent forms of EC-1 peptide with the Fc portion of the human IgG and bionanocapsule modified with ZZ-tag on its surface to improve the interaction with ErbB2. These forms showed higher affinity to ErbB2 than that of EC-1 monomer. Furthermore, prominent endosomal accumulation of ErbB2 occurred in SK-BR-3 cells when stimulated with EC-Fc ligand multivalently displayed on the surface of the bionanocapsule, whereas SK-BR-3 cells as themselves displayed stringent mechanism against ErbB2 internalization without stimulation. The multivalent form of EC-1 peptide appeared to internalize ErbB2 more efficiently than divalent form did. This internalization was unaffected by the inhibition of clathrin association, but inhibited when the cholesterol was depleted which explained either caveolar or GPI-AP-early endocytic compartment (GEEC) pathway. Because of the lack of caveolin-1 expression, caveolar machinery may be lost in SK-BR-3 cell line. Therefore, it is suggested that the multivalent form of EC-1 induces the internalization of ErbB2 through the GEEC pathway.

  7. The rat ErbB2 tyrosine kinase receptor produced in plants is immunogenic in mice and confers protective immunity against ErbB2(+) mammary cancer.

    Science.gov (United States)

    Matić, Slavica; Quaglino, Elena; Arata, Lucia; Riccardo, Federica; Pegoraro, Mattia; Vallino, Marta; Cavallo, Federica; Noris, Emanuela

    2016-01-01

    The rat ErbB2 (rErbB2) protein is a 185-kDa glycoprotein belonging to the epidermal growth factor-related proteins (ErbB) of receptor tyrosine kinases. Overexpression and mutations of ErbB proteins lead to several malignancies including breast, lung, pancreatic, bladder and ovary carcinomas. ErbB2 is immunogenic and is an ideal candidate for cancer immunotherapy. We investigated the possibility of expressing the extracellular (EC) domain of rErbB2 (653 amino acids, aa) in Nicotiana benthamiana plants, testing the influence of the 23 aa transmembrane (TM) sequence on protein accumulation. Synthetic variants of the rErbB2 gene portion encoding the EC domain, optimized with a human codon usage and either linked to the full TM domain (rErbB2_TM, 676 aa), to a portion of it (rErbB2-pTM, 662 aa), or deprived of it (rErbB2_noTM, 653 aa) were cloned in the pEAQ-HT expression vector as 6X His tag fusions. All rErbB2 variants (72-74.5 kDa) were transiently expressed, but the TM was detrimental for rErbB2 EC accumulation. rERbB2_noTM was the most expressed protein; it was solubilized and purified with Nickel affinity resin. When crude soluble extracts expressing rErbB2_noTM were administered to BALB/c mice, specific rErbB2 immune responses were triggered. A potent antitumour activity was induced when vaccinated mice were challenged with syngeneic transplantable ErbB2(+) mammary carcinoma cells. To our knowledge, this is the first report of expression of rErbB2 in plants and of its efficacy in inducing a protective antitumour immune response, opening interesting perspectives for further immunological testing.

  8. ErbB2 inhibition by lapatinib promotes degradation of mutant p53 protein in cancer cells.

    Science.gov (United States)

    Li, Dun; Marchenko, Natalia D

    2017-01-24

    Mutations in the p53 tumor suppressor gene are the most prevalent genetic events in human Her2-positive breast cancer and are associated with poor prognosis and survival. Human clinical data and our in vitro and in vivo studies strongly suggest potent oncogenic cooperation between mutant p53 and Her2 (ErbB2). Yet, the translational significance of mutant p53 in Her2 positive breast cancer, especially with respect to Her2-targeted therapies, has not been evaluated. Our previous work identified novel oncogenic activity of mutant p53 whereby mutp53 amplifies ErbB2 signaling via the mutp53-HSF1-ErbB2 feed-forward loop. Here we report that pharmacological interception of this circuit by ErbB2 inhibitor lapatinib downregulates mutant p53 in vitro and in vivo. We found that ErbB2 inhibition by lapatinib inhibits transcription factor HSF1, and its target Hsp90, followed by mutant p53 degradation in MDM2 dependent manner. Thus, our data suggest that mutant p53 sensitizes cancer cells to lapatinib via two complementary mechanisms: mutant p53 mediated amplification of ErbB2 signaling, and simultaneous annihilation of both potent oncogenic drivers, ErbB2 and mutant p53. Hence, our study could provide valuable information for the optimization of therapeutic protocols to achieve superior clinical effects in the treatment of Her2 positive breast cancer.

  9. Expression and function of Neuregulin 1 and its signaling system ERBB2/3 in the enteric nervous system

    Directory of Open Access Journals (Sweden)

    Martina eBarrenschee

    2015-09-01

    Full Text Available Neuregulin 1 (NRG1 is suggested to promote the survival and maintenance of the enteric nervous system (ENS. As deficiency in its corresponding receptor signaling complex ERBB2/ERBB3 leads to postnatal colonic hypo/aganglionosis we assessed the distributional and expressional pattern of the NRG1-ERBB2/ERBB3 system in the human colon and explored the neurotrophic capacity of NRG1 on cultured enteric neurons.Site-specific mRNA expression of the NRG1-ERBB2/3 system was determined in microdissected samples harvested from enteric musculature and ganglia. Localization of NRG1, ERBB2 and ERBB3 was determined by dual-label-immunohistochemistry using pan-neuronal and pan-glial markers. Morphometric analysis was performed on NRG1-stimulated rat enteric nerve cultures to evaluate neurotrophic effects. mRNA expression of the NRG1-ERBB2/3 system was determined by qPCR. Co-localization of NRG1 with neuronal or synaptic markers was analyzed in enteric nerve cultures stimulated with glial cell line-derived neurotrophic factor (GDNF. The NRG1 system was expressed in both neurons and glial cells of enteric ganglia and in nerve fibers. NRG1 significantly enhanced growth parameters in enteric nerve cell cultures and ErB3 mRNA expression was down-regulated upon NRG1 stimulation. GDNF negatively regulates ErbB2 and ErbB3 mRNA expressionThe NRG1-ERBB2/3 system is physiologically present in the human ENS and NRG1 acts as a neurotrophic factor for the ENS. The down-regulation of ErbB3/ErbB2 in GDNF stimulated nerve cell cultures points to an interaction of both neurotrophic factors. Thus, the data may provide a basis to assess disturbed signaling components of the NRG1 system in enteric neuropathies.

  10. Transactivation of EGF receptor and ErbB2 protects intestinal epithelial cells from TNF-induced apoptosis.

    Science.gov (United States)

    Yamaoka, Toshimitsu; Yan, Fang; Cao, Hanwei; Hobbs, Stuart S; Dise, Rebecca S; Tong, Wei; Polk, D Brent

    2008-08-19

    TNF is a pleiotropic cytokine that activates both anti- and proapoptotic signaling pathways, with cell fate determined by the balance between these two pathways. Activation of ErbB family members, including EGF receptor (EGFR/ErbB1), promotes cell survival and regulates several signals that overlap with those stimulated by TNF. This study was undertaken to determine the effects of TNF on EGFR and ErbB2 activation and intestinal epithelial cell survival. Mice, young adult mouse colon epithelial cells, and EGFR knockout mouse colon epithelial cells were treated with TNF. Activation of EGFR, ErbB2, Akt, Src, and apoptosis were determined in vivo and in vitro. TNF stimulated EGFR phosphorylation in young adult mouse colon epithelial cells, and loss of EGFR expression or inhibition of kinase activity increased TNF-induced apoptosis, which was prevented in WT but not by kinase-inactive EGFR expression. Similarly, TNF injection stimulated apoptosis in EGFR-kinase-defective mice (EGFR(wa2)) compared with WT mice. TNF also activated ErbB2, and loss of ErbB2 expression increased TNF-induced apoptosis. Furthermore, Src-kinase activity and the expression of both EGFR and ErbB2 were required for TNF-induced cell survival. Akt was shown to be a downstream target of TNF-activated EGFR and ErbB2. These findings demonstrate that EGFR and ErbB2 are critical mediators of TNF-regulated antiapoptotic signals in intestinal epithelial cells. Given evidence for TNF signaling in the development of colitis-associated carcinoma, this observation has significant implications for understanding the role of EGFR in maintaining intestinal epithelial cell homeostasis during cytokine-mediated inflammatory responses.

  11. High expression of ErbB2 contributes to cholangiocarcinoma cell invasion and proliferation through AKT/p70S6K

    Institute of Scientific and Technical Information of China (English)

    Warapen; Treekitkarnmongkol; Tuangporn; Suthiphongchai

    2010-01-01

    AIM:To compare the impact of ErbB2 on cell invasion and proliferation in cholangiocarcinoma(CCA) cell lines.METHODS:Level of endogenous ErbB2 expression in three CCA cell lines,namely HuCCA-1,KKU-100 and KKU-M213,was determined by real-time reversetranscriptase polymerase chain reaction.Two ErbB2 inhibitory methods,a small molecule ErbB2 kinase inhibitor(AG825) and siRNA,were used to disrupt ErbB2 function in the cell lines.CCA cell invasion,motility and proliferation under ErbB2-disrupted conditions were d...

  12. Clinical relevance of ErbB-2/HER2 nuclear expression in breast cancer

    Directory of Open Access Journals (Sweden)

    Schillaci Roxana

    2012-02-01

    Full Text Available Abstract Background The biological relevance of nuclear ErbB-2/HER2 (NuclErbB-2 presence in breast tumors remains unexplored. In this study we assessed the clinical significance of ErbB-2 nuclear localization in primary invasive breast cancer. The reporting recommendations for tumor marker prognostic studies (REMARK guidelines were used as reference. Methods Tissue microarrays from a cohort of 273 primary invasive breast carcinomas from women living in Chile, a Latin American country, were examined for membrane (MembErbB-2 and NuclErbB-2 expression by an immunofluorescence (IF protocol we developed. ErbB-2 expression was also evaluated by immunohistochemistry (IHC with a series of antibodies. Correlation between NuclErbB-2 and MembErbB-2, and between NuclErbB-2 and clinicopathological characteristics of tumors was studied. The prognostic value of NuclErbB-2 in overall survival (OS was evaluated using Kaplan-Meier method, and Cox model was used to explore NuclErbB-2 as independent prognostic factor for OS. Results The IF protocol we developed showed significantly higher sensitivity for detection of NuclErbB-2 than IHC procedures, while its specificity and sensitivity to detect MembErbB-2 were comparable to those of IHC procedures. We found 33.6% NuclErbB-2 positivity, 14.2% MembErbB-2 overexpression by IF, and 13.0% MembErbB-2 prevalence by IHC in our cohort. We identified NuclErbB-2 positivity as a significant independent predictor of worse OS in patients with MembErbB-2 overexpression. NuclErbB-2 was also a biomarker of lower OS in tumors that overexpress MembErbB-2 and lack steroid hormone receptors. Conclusions We revealed a novel role for NuclErbB-2 as an independent prognostic factor of poor clinical outcome in MembErbB-2-positive breast tumors. Our work indicates that patients presenting NuclErbB-2 may need new therapeutic strategies involving specific blockage of ErbB-2 nuclear migration.

  13. Mechanisms of Trastuzumab resistance in ErbB2-driven breast cancer and newer opportunities to overcome therapy resistance

    Directory of Open Access Journals (Sweden)

    Tameka A Bailey

    2011-01-01

    Full Text Available The Human Epidermal Growth Factor Receptor 2 (Her2, ErbB2 or Neu is overexpressed in about 20 - 25% of breast cancers and is causally linked to oncogenesis, providing opportunities for targeted therapy. Trastuzumab (Herceptin™, Genentech Inc, San Francisco, CA, a humanized monoclonal antibody against ErbB2, is a successful example of this concept and has vastly improved the response to treatment and overall survival in a majority of ErbB2+ breast cancer patients. However, lack of response in some patients as well as relapse during the course of therapy in others, continue to challenge researchers and clinicians alike towards a better understanding of the fundamental mechanisms of Trastuzumab action and resistance to treatment. The exact in vivo mechanism of action of Trastuzumab remains enigmatic, given its direct effects on the ErbB2 signaling pathway as well as indirect contributions from the immune system, by virtue of the ability of Trastuzumab to elicit Antibody-Dependent Cellular Cytotoxicity. Consequently, multiple mechanisms of resistance have been proposed. We present here a comprehensive review of our current understanding of the mechanisms, both of Trastuzumab action and clinical resistance to Trastuzumab-based therapies. We also review newer strategies (based on ErbB2 receptor biology that are being explored to overcome resistance to Trastuzumab therapy.

  14. The deaf and the dumb: the biology of ErbB-2 and ErbB-3.

    Science.gov (United States)

    Citri, Ami; Skaria, Kochupurakkal Bose; Yarden, Yosef

    2003-03-10

    ErbB-2 (also called HER2/neu) and ErbB-3 are closely related to the epidermal growth factor receptor (EGFR/ErbB-1), but unlike EGFR, ErbB-2 is a ligandless receptor, whereas ErbB-3 lacks tyrosine kinase activity. Hence, both ErbB-2 and ErbB-3 are active only in the context of ErbB heterodimers, and ErbB-2. ErbB-3 heterodimers, which are driven by neuregulin ligands, are the most prevalent and potent complexes. These stringently controlled heterodimers are repeatedly employed throughout embryonic development and dictate the establishment of several cell lineages through mesenchyme-epithelial inductive processes and the interactions of neurons with muscle, glia, and Schwann cells. Likewise, the potent combination of signaling pathways engaged by the heterodimers drives an aggressive phenotype of tumors of secretory epithelia, including breast and lung cancers. This review highlights recent structural insights into the mechanism of ligand-induced heterodimer formation, and concentrates on signaling pathways employed by ErbB-2 and ErbB-3 in normal and in malignant cells.

  15. Nf2/Merlin controls spinal cord neural progenitor function in a Rac1/ErbB2-dependent manner.

    Directory of Open Access Journals (Sweden)

    Cynthia Garcia

    Full Text Available OBJECTIVE: Individuals with the neurofibromatosis type 2 (NF2 cancer predisposition syndrome develop spinal cord glial tumors (ependymomas that likely originate from neural progenitor cells. Whereas many spinal ependymomas exhibit indolent behavior, the only treatment option for clinically symptomatic tumors is surgery. In this regard, medical therapies are unfortunately lacking due to an incomplete understanding of the critical growth control pathways that govern the function of spinal cord (SC neural progenitor cells (NPCs. METHODS: To identify potential therapeutic targets for these tumors, we leveraged primary mouse Nf2-deficient spinal cord neural progenitor cells. RESULTS: We demonstrate that the Nf2 protein, merlin, negatively regulates spinal neural progenitor cell survival and glial differentiation in an ErbB2-dependent manner, and that NF2-associated spinal ependymomas exhibit increased ErbB2 activation. Moreover, we show that Nf2-deficient SC NPC ErbB2 activation results from Rac1-mediated ErbB2 retention at the plasma membrane. SIGNIFICANCE: Collectively, these findings establish ErbB2 as a potential rational therapeutic target for NF2-associated spinal ependymoma.

  16. Egf binding to its receptor triggers a rapid tyrosine phosphorylation of the erbB-2 protein in the mammary tumor cell line SK-BR-3.

    OpenAIRE

    King, C. R.; Borrello, I; Bellot, F; Comoglio, P; Schlessinger, J

    1988-01-01

    The epidermal growth factor receptor (EGF-R) and the erbB-2 proto-oncogene product protein are closely related by their structural homology and their shared enzymatic activity as autophosphorylating tyrosine kinases. We show that in mammary tumor cells (SK-BR-3) EGF causes a rapid increase in tyrosine phosphorylation of the erbB-2 protein. Phosphorylation of erbB-2 does not occur in cells lacking the EGF-R (MDA-MB-453). Phosphorylation of erbB-2 in SK-BR-3 cells is blocked if EGF is prevented...

  17. Dynamic transcription factor activity and networks during ErbB2 breast oncogenesis and targeted therapy.

    Science.gov (United States)

    Weiss, M S; Peñalver Bernabé, B; Shin, S; Asztalos, S; Dubbury, S J; Mui, M D; Bellis, A D; Bluver, D; Tonetti, D A; Saez-Rodriguez, J; Broadbelt, L J; Jeruss, J S; Shea, L D

    2014-12-01

    Tissue development and disease progression are multi-stage processes controlled by an evolving set of key regulatory factors, and identifying these factors necessitates a dynamic analysis spanning relevant time scales. Current omics approaches depend on incomplete biological databases to identify critical cellular processes. Herein, we present TRACER (TRanscriptional Activity CEll aRrays), which was employed to quantify the dynamic activity of numerous transcription factor (TFs) simultaneously in 3D and networks for TRACER (NTRACER), a computational algorithm that allows for cellular rewiring to establish dynamic regulatory networks based on activity of TF reporter constructs. We identified major hubs at various stages of culture associated with normal and abnormal tissue growth (i.e., ELK-1 and E2F1, respectively) and the mechanism of action for a targeted therapeutic, lapatinib, through GATA-1, which were confirmed in human ErbB2 positive breast cancer patients and human ErbB2 positive breast cancer cell lines that were either sensitive or resistant to lapatinib.

  18. Electrocardiographic Characterization of Cardiac Hypertrophy in Mice that Overexpress the ErbB2 Receptor Tyrosine Kinase

    DEFF Research Database (Denmark)

    Sysa-Shah, Polina; Sørensen, Lars L; Abraham, M Roselle

    2015-01-01

    , the ECG recordings of ErbB2(tg) mice were characterized by higher P- and R-wave amplitudes, broader QRS complexes, inverted T waves, and ST interval depression. Pearson's correlation matrix analysis of combined WT and ErbB2(tg) data revealed significant correlation between heart weight and the ECG...... parameters of QT interval (corrected for heart rate), QRS interval, ST height, R amplitude, P amplitude, and PR interval. In addition, the left ventricular posterior wall thickness as determined by echocardiography correlated with ECG-determined ST height, R amplitude, QRS interval; echocardiographic left...... ventricular mass correlated with ECG-determined ST height and PR interval. In summary, we have determined phenotypic ECG criteria to differentiate ErbB2(tg) from WT genotypes in 98.8% of mice. This inexpensive and time-efficient ECG-based phenotypic method might be applied to differentiate between genotypes...

  19. p53 and erbB-2 Are Not Associated in Matched Cases of Primary and Metastatic Ovarian Carcinomas

    Directory of Open Access Journals (Sweden)

    Cristina Rodríguez-Burford

    2003-01-01

    Full Text Available Ovarian cancer has a high mortality rate largely due to the limited number of ovarian carcinomas detected at an early stage. Understanding the molecular changes occurring during the progression of ovarian carcinoma would aid in the development of therapies that may inhibit or target metastasis. Primary and metastatic lesions from 54 and 40 patients with advanced ovarian carcinoma, respectively (including matched primary and metastatic lesions from 30 patients were evaluated for nuclear accumulation of p53 (clone BP53-12-1 and cytoplasmic and membranous immunostaining of p185 erbB-2 (clone 3B5 by immunohistochemistry. No differences in the immunostaining of p53 and p185erbB-2 (cytoplasm or membrane were observed between primary and metastatic lesions of the matched cases. Similarly, no differences in the proportion of positive cases of p53 between primary and metastatic lesions of the matched cases was observed. Thus, novel therapies that target p53 or p185erbB-2 can utilize specimens from either primary or metastatic lesions to characterize these targets prior to therapy. Spearman correlations between p53 and p185erbB-2 (cytoplasm or membrane immunohistochemistry scores were insignificant for the matched cases, all primary lesions, and all metastatic lesions. Also, no significant associations occurred between nuclear accumulation of p53 (positive versus negative and phenotypic expression of p185erbB-2 (cytoplasm or membrane immunostaining scores for the matched cases, all primary lesions, and all metastatic lesions. Thus, the nuclear accumulation of p53 and immunostaining of p185erbB-2 in the cytoplasm or on the cellular membranes are independent.

  20. A novel mouse monoclonal antibody targeting ErbB2 suppresses breast cancer growth

    Energy Technology Data Exchange (ETDEWEB)

    Kawa, Seiji [Division of Oncology, Institute of Medical Science, University of Tokyo, Shirokanedai 4-6-1, Minato-ku, Tokyo 108-8639 (Japan); Matsushita, Hirohisa; Ohbayashi, Hirokazu [Department of Research and Development, Nichirei Biosciences Inc., Tokyo 104-8402 (Japan); Semba, Kentaro [Department of Life Science and Medical Bio-Science, School of Science and Engineering, Waseda University, Tokyo 169-8555 (Japan); Yamamoto, Tadashi, E-mail: tyamamot@ims.u-tokyo.ac.jp [Division of Oncology, Institute of Medical Science, University of Tokyo, Shirokanedai 4-6-1, Minato-ku, Tokyo 108-8639 (Japan)

    2009-07-03

    Overexpression of ErbB2 in breast cancer is associated with increased recurrence and worse prognosis. Accumulating evidences suggest that molecular targeted therapy is a promising anticancer strategy. In this study, we produced a novel anti-ErbB2 monoclonal antibody, 6G10, that recognized an epitope distinct from the trastuzumab binding site. 6G10 induced aggregation of BT474 breast cancer cells and inhibited proliferation of various breast cancer cell lines including BT474. A growth inhibition assay showed that 6G10 had EC{sub 50} values comparable to trastuzumab, indicating that the drugs have a similar level of potency. Furthermore, intraperitoneal administration of 6G10 completely inhibited the growth of xenografted tumors derived from BT474 and SK-BR-3 cells. These data suggested that 6G10 has great therapeutic potential and could be administered to patients alternatively, or synergistically, with trastuzumab.

  1. ErbB2, but not ErbB1, reinitiates proliferation and induces luminal repopulation in epithelial acini

    Energy Technology Data Exchange (ETDEWEB)

    Muthuswamy, Senthil K; Li, Dongmei; Lelievre, Sophie; Bissell, Mina J; Brugge, Joan S

    2001-08-08

    Both ErbB1 and ErbB2 are overexpressed or amplified in breast tumors. To examine the effects of activating ErbB receptors in a context that mimics polarized epithelial cells in vivo, we activated ErbB1 and ErbB2 homodimers in preformed, growth-arrested mammary acini cultured in three-dimensional basement membrane gels. Activation of ErbB2, but not that of ErbB1, led to a reinitiation of cell proliferation and altered the properties of mammary acinar structures. These altered structures share several properties with early-stage tumors, including a loss of proliferative suppression, an absence of lumen, retention of the basement membrane and a lack of invasive properties. ErbB2 activation also disrupted tight junctions and the cell polarity of polarized epithelia, whereas ErbB1 activation did not have any effect. Our results indicate that ErbB receptors differ in their ability to induce early stages of mammary carcinogenesis in vitro and this three-dimensional model system can reveal biological activities of oncogenes that cannot be examined in vitro in standard transformation assays.

  2. Examining ERBB2 as a candidate gene for susceptibility to leprosy (Hansen’s disease in Brazil

    Directory of Open Access Journals (Sweden)

    Sérgio Ricardo Fernandes Araújo

    2014-04-01

    Full Text Available Leprosy remains prevalent in Brazil. ErbB2 is a receptor for leprosy bacilli entering Schwann cells, which mediates Mycobacterium leprae-induced demyelination and the ERBB2 gene lies within a leprosy susceptibility locus on chromosome 17q11-q21. To determine whether polymorphisms at the ERBB2 locus contribute to this linkage peak, three haplotype tagging single nucleotide polymorphisms (tag-SNPs (rs2517956, rs2952156, rs1058808 were genotyped in 72 families (208 cases; 372 individuals from the state of Pará (PA. All three tag-SNPs were associated with leprosy per se [best SNP rs2517959 odds ratio (OR = 2.22; 95% confidence interval (CI 1.37-3.59; p = 0.001]. Lepromatous (LL (OR = 3.25; 95% CI 1.37-7.70; p = 0.007 and tuberculoid (TT (OR = 1.79; 95% CI 1.04-3.05; p = 0.034 leprosy both contributed to the association, which is consistent with the previous linkage to chromosome 17q11-q21 in the population from PA and supports the functional role of ErbB2 in disease pathogenesis. To attempt to replicate these findings, six SNPs (rs2517955, rs2517956, rs1810132, rs2952156, rs1801200, rs1058808 were genotyped in a population-based sample of 570 leprosy cases and 370 controls from the state of Rio Grande do Norte (RN and the results were analysed using logistic regression analysis. However, none of the associations were replicated in the RN sample, whether analysed for leprosy per se, LL leprosy, TT leprosy, erythema nodosum leprosum or reversal reaction conditions. The role of polymorphisms at ERBB2 in controlling susceptibility to leprosy in Brazil therefore remains unclear.

  3. Analysis of protein-protein interactions involved in the activation of the Shc/Grb-2 pathway by the ErbB-2 kinase.

    Science.gov (United States)

    Ricci, A; Lanfrancone, L; Chiari, R; Belardo, G; Pertica, C; Natali, P G; Pelicci, P G; Segatto, O

    1995-10-19

    In murine fibroblasts activation of the Shc/Grb-2 pathway by the ErbB-2 kinase involves tyrosine phosphorylation of Shc products and the formation of Shc/ErbB-2, Shc/Grb-2 and Grb-2/ErbB-2 complexes. Tyr 1139 of ErbB-2 bound to the Grb-2 SH2 domain in vitro as well as in intact cells. Tyr 1221 and 1248 are binding sites of gp185ErbB-2 for Shc SH2 domain in vitro whereas Tyr 1196 and 1248 are major binding sites of ErbB-2 for Shc PTB domain. Inhibition of Shc/ErbB-2 complex formation in intact cells was obtained by simultaneous mutational inactivation of Shc SH2 and Shc PTB binding sites of gp185ErbB-2. Shc/ErbB-2 complexes are formed upon activation of the ErbB-2 kinase and tyrosine phosphorylation of Shc proteins; they are located in both cytosol and cellular membranes. ErbB-2 activation induces also translocation of Grb-2 from cytosol to membranes. This network of protein-protein interactions may reflect the ability of the Shc/Grb-2 pathway to act as a molecular switch controlling different cellular functions regulated by RTK activation. In fact the Ras GDP exchanger mSOS was recruited in Grb-2/ErbB-2 complexes; furthermore besides mSOS, other polypeptides present in either cytosolic or membrane preparations were able to complex in vitro with Grb-2 SH3 domains.

  4. Reliable PCR quantitation of estrogen, progesterone and ERBB2 receptor mRNA from formalin-fixed, paraffin-embedded tissue is independent of prior macro-dissection

    DEFF Research Database (Denmark)

    Tramm, Trine; Hennig, Guido; Kyndi, Marianne

    2013-01-01

    receptor 2 (ERBB2), by comparing gene expression from whole slide and tumor-enriched sections, and correlating gene expression from whole slide sections with corresponding immunohistochemistry. Gene expression, based on mRNA extracted from a training set (36 paraffin blocks) and two validation sets (133...... and ERBB2, and 83 % for PGR. Overall agreements, when comparing mRNA expression to immunohistochemistry, were 100 % (ERBB2), 89 % (ESR1) and 83 % (PGR), which was confirmed in the validation sets. Percentage of tumor in the sections did not influence the results. In conclusion, reliable quantification...

  5. Effects of Neuregulins on Invasion and Metastasis of Non-overexpression ErbB2 Breast Cancer Cells

    Institute of Scientific and Technical Information of China (English)

    Ya-mei Zhang; Ting-ting Zhao; Hua-yu Deng

    2009-01-01

    Objective: To explore the effects of neuregulins on ErbB2 receptor signal transduction pathway activation, and invasion and metastasis of non-overexpression ErbB2 breast cancer cell MDA-MB-231. Methods: The expressions of neuregulin were detected by immunocytochemistry and Western blot. MDA-MB-231 cells were treated with ErbB2 kinase inhibitor AG825. Proliferations were measured with MTT assay. Invasion and metastasis of MDA-ME-231 cells were evaluated with transwell chamber. The enzyme activities of MMP-2 and MMP-9 were detected by gelatin zymography. The expressions of MMP-2 and HIF-1α were detected by Western blot.Results: MDA-MB-231 cells expressed a relatively higher level of neuregulin. In Western blot, the positive reaction band was found at 44KD which coincides with the molecular weight of NRG. When MDA-MB-231 cells were treated with AG825, the proliferation was inhibited in a time-dose-dependent manner (P<0.01), invasion and metastasis were also depressed (P<0.05). The enzyme activities of MMP-2 and MMP-9 were lower (P<0.05). The expression levels of MMP-2 and HIF-1α were decreased (P<0.05).Conclusion: Our study indicates that neuregulins are synthesized in MDA-MB-231 cells as transmembrane proteins, neuregulins could activate ErbB2 receptor signal transduction pathway by autocrine or paracrine secretion, and induce invasion and metastasis of MDA-MB-231 cells.

  6. Transcriptome analysis of basal and luminal tumor-initiating cells in ErbB2-driven breast cancer

    Directory of Open Access Journals (Sweden)

    Nicholas Borcherding

    2015-06-01

    Full Text Available Breast cancer is the leading cause of cancer-related mortality for females worldwide [1]. Improving early screening strategies and understanding the events that lead to tumor initiation have led to demonstrable improvements in clinical outcome. Our previous work revealed a variance in the tumorigenic capacity between different mammary epithelial cell populations in an MMTV-ErbB2 mouse model. In order to greater understand how different mammary epithelial cells influence the tumorigenic capacity in ErbB2-induced breast cancer, we transplanted different cell populations from pre-neoplastic MMTV-ErbB2 female mice into recipient mice for tumorigenic study. We found that different mammary epithelial cells bear different tumorigenic potentials even when induced by the same ErbB2 proto-oncogene. To understand the difference in tumors formed from different epithelial cells, we performed gene expression profiling using these tumors (GSE64487. Several genes were further validated using real-time reverse transcription polymerase chain reaction (RT-PCR. Here we provide further details on the experimental methods and microarray analysis. This data provides a resource to further understanding how different mammary cell populations can initiate ErbB2-driven tumors and the role of these cell populations as putative tumor-initiating cells (TICs.

  7. C-ERBB2促小鼠卵母细胞成熟及在表皮生长因子调控小鼠卵母细胞体外成熟中的作用%Potential roles of the C-ERBB2 protooncogene in mouse oocyte maturation and in conducting EGF promoting mouse oocyte maturation in vitro

    Institute of Scientific and Technical Information of China (English)

    郑莉萍; 汪小浪; 吴磊; 郑月慧; 高凤兰; 肖秋香; 李芳

    2006-01-01

    目的 探讨C-ERBB2对小鼠卵母细胞成熟的影响及对表皮生长因子在卵母细胞成熟调控中的作用.方法 采用卵母细胞体外培养法,研究反义C-ERBB2寡脱氧核苷酸(C-ERBB2 ASODN)对卵母细胞体外自发成熟及对表皮生长因子(EGF)促卵母细胞成熟的影响;利用RT-PCR检测卵母细胞中C-ERBB2 mRNA的表达及在不同处理因素作用下卵母细胞成熟过程中C-ERBB2 mRNA表达的变化.结果 C-ERBB2 ASODN能呈剂量依赖方式抑制卵母细胞的生发泡破裂(GVBD)率和第一极体(PBⅠ)排出率,并且能抑制EGF对卵母细胞的促成熟作用.卵母细胞中存在C-ERBB2 mRNA,EGF可以增强其表达,C-ERBB2 ASODN可减弱EGF促表达的作用.结论 C-ERBB2与卵母细胞的成熟密切相关.EGF可直接促进裸卵的成熟分裂,其机制可能与上调卵母细胞C-ERBB2的表达有关.

  8. ErbB2-Driven Breast Cancer Cell Invasion Depends on a Complex Signaling Network Activating Myeloid Zinc Finger-1-Dependent Cathepsin B Expression

    DEFF Research Database (Denmark)

    Rafn, Bo; Nielsen, Christian Thomas Friberg; Andersen, Sofie Hagel;

    2012-01-01

    signaling network activates the transcription of cathepsin B gene (CTSB) via myeloid zinc finger-1 transcription factor that binds to an ErbB2-responsive enhancer element in the first intron of CTSB. This work provides a model system for ErbB2-induced breast cancer cell invasiveness, reveals a signaling...... network that is crucial for invasion in vitro, and defines a specific role and targets for the identified serine-threonine kinases....

  9. Gene amplification and immunohistochemical expression of ERBB2 and EGFR in cervical carcinogenesis. Correlation with cell-cycle markers and HPV presence.

    Science.gov (United States)

    Conesa-Zamora, Pablo; Torres-Moreno, Daniel; Isaac, María A; Pérez-Guillermo, Miguel

    2013-10-01

    Although the members of the epidermal growth factor receptor family ERBB2 and EGFR are important therapeutic targets in the treatment of malignant neoplasias, little is known about their role in cervical carcinogenesis. Our objective was to evaluate the dysfunction of ERBB2 and EGFR at the gene copy number and protein expression level in neoplastic lesions of the uterine cervix with the aim of obtaining information about its role in cervical carcinogenesis and their possible use as therapeutic targets in these diseases. We studied gene amplification and protein expression of ERBB2 and EGFR and their relationship with Ki67, p16 and p53 and HPV presence in 22 normal/benign (N/B) cervices, 20 low-grade squamous intraepithelial lesions (LSILs), 70 high-grade SILs (HSILs) and 32 invasive squamous cervical carcinomas (ISCCs). No cases showed selective amplification of ERBB2 or EGFR but corresponding chromosome-specific probes displayed chromosome 17 and 7 polyploidy associated with the grade of the lesion (plesions (N/B plus LSIL 21.4% vs. HSIL plus ISCC 45.5%; p=0.007). No association was observed between EGFR expression and that of cell-cycle markers or HPV presence. Increased copy number of EGFR and ERBB2 is due to polyploidy of 7 and 17 chromosomes, this being a phenomenon associated with lesion severity and with an increase in the expression of cell-cycle markers. EGFR, but not ERBB2, is expressed in precursor lesions of squamous cervical neoplasia and is related to the neoplastic progression but not to proliferation marker expression and therefore ERBB2 and this calls into question the usefulness of ERBB2 as a therapeutic target.

  10. ErbB2 overexpression on occult metastatic cells in bone marrow predicts poor clinical outcome of stage I-III breast cancer patients.

    Science.gov (United States)

    Braun, S; Schlimok, G; Heumos, I; Schaller, G; Riethdorf, L; Riethmüller, G; Pantel, K

    2001-03-01

    Occult hematogenous micrometastases are the major cause for metastatic relapse and cancer-related death in patients with operable primary breast cancer. Although sensitive immunocytochemical and molecular methods allow detection of individual breast cancer cells in bone marrow (BM), a major site of metastatic relapse, current detection techniques cannot discriminate between nonviable shed tumor cells and seminal metastatic cells. To address this problem, we analyzed the relevance of erbB2 overexpression on disseminated cytokeratin-18-positive breast cancer cells in the BM of 52 patients with locoregionally restricted primary breast cancer using immunocytochemical double labeling with monoclonal antibody 9G6 to the p185erbB2 oncoprotein. Expression of p185erbB2 on BM micrometastases was detected in 31 of 52 (60%) patients independent of established risk factors such as lymph node involvement, primary tumor size, differentiation grade, or expression of p185erbB2 on primary tumor cells. After a median follow-up of 64 months, patients with p185erbB2-positive BM micrometastases had developed fatal metastatic relapses more frequently than patients with p185erbB2-negative micrometastases (21 versus 7 events; P = 0.032). In multivariate analysis, the presence of p185erbB2-positive micrometastases was an independent prognostic factor with a hazard ratio of 2.78 (95% confidence interval, 1.11-6.96) for overall survival (P = 0.029). We therefore conclude that erbB2 overexpression characterizes a clinically relevant subset of breast cancer micrometastases.

  11. Detection of soluble ERBB2 in breast cancer cell lysates using a combined label-free/fluorescence platform based on Bloch surface waves.

    Science.gov (United States)

    Sinibaldi, Alberto; Sampaoli, Camilla; Danz, Norbert; Munzert, Peter; Sibilio, Leonardo; Sonntag, Frank; Occhicone, Agostino; Falvo, Elisabetta; Tremante, Elisa; Giacomini, Patrizio; Michelotti, Francesco

    2017-06-15

    We report on the use of one-dimensional photonic crystals to detect clinically relevant concentrations of ERBB2/neu/Her2 in cell lysates. ERBB2 is a pivotal breast cancer biomarker and targetable oncogenic driver associated with aggressive breast cancer subtypes. To quantitate soluble ERBB2, we developed an optical platform that combines label-free and fluorescence detection modes. Such platform makes use of a sandwich assay in which the one-dimensional photonic crystals sustaining Bloch surface waves are tailored with a monoclonal antibody for highly specific biological recognition (BSW biochip). In a second step, a second antibody to ERBB2 quantitatively detects the bound analyte. The strategy of the present approach takes advantage of the combination of label-free and fluorescence techniques, making bio-recognition more robust and sensitive. In the fluorescence operation mode, the platform can attain the limit of detection 0.3ng/mL (1.5pM) for ERBB2 in cell lysates. Such resolution meets the international guidelines and recommendations (15ng/mL) for diagnostic ERBB2 assays that in the future may help to more precisely assign therapies counteracting cancer cell proliferation and metastatic spread.

  12. Differential Gene Expression of BRCA1,ERBB2 and TP53 biomarkers between Human Breast Tissue and Peripheral Blood Samples of Breast Cancer.

    Science.gov (United States)

    Zghair, Abdulrazzaq Neamah; Sinha, Deepak Kumar; Kassim, Arkan; Alfaham, Mohmmad; Sharma, Anil K

    2016-01-01

    Breast cancer is a most common malignancy especially in Iraqi women accounting for high morbidity and mortality. Mutations in BRCA1 gene is one of the important genetic predisposing factors inbreast cancer. Similarly ERBB2 and TP53 are also key prognostic markers in breast cancer treatment.We were interested to explore the gene expression profiles of BRCA1, ERBB2 and TP53 in breast cancer women patients from Iraq so as to assess the potential of such markers in breast cancer treatment. The mRNA levels were significantly over-expressed in tumor tissues in comparison to normal ones with p values (pTP53 and benign tissue samples as well. However in blood samples, no considerable expression of these markers was observed. Out of three selected genes, ERBB2 expression was significantly expressed in comparison to BRCA1 and TP53 in cancer tissue. Mutation analysis of BRCA1, ERBB2 and TP53 has been made to find out the region most susceptible to mutations in these genes The BRCA1 exon 11, ERBB2 16 and TP53 exon 5 displayed increased chances of having mutations. We can conclude from the study that differential gene expression of BRCA1, ERBB2 and TP53 at mRNA levels may act as a diagnostic marker of circulating tumor cells having important prognostic value in breast cancer patients.

  13. Cardiac-specific over-expression of epidermal growth factor receptor 2 (ErbB2 induces pro-survival pathways and hypertrophic cardiomyopathy in mice.

    Directory of Open Access Journals (Sweden)

    Polina Sysa-Shah

    Full Text Available BACKGROUND: Emerging evidence shows that ErbB2 signaling has a critical role in cardiomyocyte physiology, based mainly on findings that blocking ErbB2 for cancer therapy is toxic to cardiac cells. However, consequences of high levels of ErbB2 activity in the heart have not been previously explored. METHODOLOGY/PRINCIPAL FINDINGS: We investigated consequences of cardiac-restricted over-expression of ErbB2 in two novel lines of transgenic mice. Both lines develop striking concentric cardiac hypertrophy, without heart failure or decreased life span. ErbB2 transgenic mice display electrocardiographic characteristics similar to those found in patients with Hypertrophic Cardiomyopathy, with susceptibility to adrenergic-induced arrhythmias. The hypertrophic hearts, which are 2-3 times larger than those of control littermates, express increased atrial natriuretic peptide and β-myosin heavy chain mRNA, consistent with a hypertrophic phenotype. Cardiomyocytes in these hearts are significantly larger than wild type cardiomyocytes, with enlarged nuclei and distinctive myocardial disarray. Interestingly, the over-expression of ErbB2 induces a concurrent up-regulation of multiple proteins associated with this signaling pathway, including EGFR, ErbB3, ErbB4, PI3K subunits p110 and p85, bcl-2 and multiple protective heat shock proteins. Additionally, ErbB2 up-regulation leads to an anti-apoptotic shift in the ratio of bcl-xS/xL in the heart. Finally, ErbB2 over-expression results in increased activation of the translation machinery involving S6, 4E-BP1 and eIF4E. The dependence of this hypertrophic phenotype on ErbB family signaling is confirmed by reduction in heart mass and cardiomyocyte size, and inactivation of pro-hypertrophic signaling in transgenic animals treated with the ErbB1/2 inhibitor, lapatinib. CONCLUSIONS/SIGNIFICANCE: These studies are the first to demonstrate that increased ErbB2 over-expression in the heart can activate protective signaling pathways and induce a phenotype consistent with Hypertrophic Cardiomyopathy. Furthermore, our work suggests that in the situation where ErbB2 signaling contributes to cardiac hypertrophy, inhibition of this pathway may reverse this process.

  14. A Functionally Significant Cross-talk between Androgen Receptor and ErbB2 Pathways in Estrogen Receptor Negative Breast Cancer

    Directory of Open Access Journals (Sweden)

    Ali Naderi

    2008-06-01

    Full Text Available Recent studies have identified novel subgroups in ER-negative breast cancer based on the expression pattern of androgen receptor (AR. One subtype (molecular apocrine has an over-expression of steroid-response genes and ErbB2. Using breast cancer cell lines with molecular apocrine features, we demonstrate a functional cross-talk between AR and ErbB2 pathways. We show that stimulation of AR and ErbB2 pathways leads to the cross-regulation of gene expression for AR, ErbB2, FOXA1, XBP1, TFF3, and KLK3. As opposed to the physiologic transient phosphorylation of extracellular signal–regulated kinase (ERK1/2 observed with the testosterone treatment, we demonstrate that the addition of ErbB2 inhibition leads to a persistent phosphorylation of ERK1/2, which negatively regulates the downstream signaling and cell growth. This suggests a mechanism for the cross-talk involving the ERK pathway. Moreover, testosterone stimulates the proliferation of molecular apocrine breast cell lines, and this effect can be reversed using antiandrogen flutamide and anti-ErbB2 AG825. Conversely, the growth stimulatory effect of heregulin can also be inhibited with flutamide, suggesting a cross-talk between the AR and ErbB2 pathways affecting cell proliferation. Importantly, there is a synergy with the combined use of flutamide and AG825 on cell proliferation and apoptosis, which indicates a therapeutic advantage in the combined blockage of AR and ErbB2 pathways.

  15. A functionally significant cross-talk between androgen receptor and ErbB2 pathways in estrogen receptor negative breast cancer.

    Science.gov (United States)

    Naderi, Ali; Hughes-Davies, Luke

    2008-06-01

    Recent studies have identified novel subgroups in ER-negative breast cancer based on the expression pattern of androgen receptor (AR). One subtype (molecular apocrine) has an over-expression of steroid-response genes and ErbB2. Using breast cancer cell lines with molecular apocrine features, we demonstrate a functional cross-talk between AR and ErbB2 pathways. We show that stimulation of AR and ErbB2 pathways leads to the cross-regulation of gene expression for AR, ErbB2, FOXA1, XBP1, TFF3, and KLK3. As opposed to the physiologic transient phosphorylation of extracellular signal-regulated kinase (ERK1/2) observed with the testosterone treatment, we demonstrate that the addition of ErbB2 inhibition leads to a persistent phosphorylation of ERK1/2, which negatively regulates the downstream signaling and cell growth. This suggests a mechanism for the cross-talk involving the ERK pathway. Moreover, testosterone stimulates the proliferation of molecular apocrine breast cell lines, and this effect can be reversed using antiandrogen flutamide and anti-ErbB2 AG825. Conversely, the growth stimulatory effect of heregulin can also be inhibited with flutamide, suggesting a cross-talk between the AR and ErbB2 pathways affecting cell proliferation. Importantly, there is a synergy with the combined use of flutamide and AG825 on cell proliferation and apoptosis, which indicates a therapeutic advantage in the combined blockage of AR and ErbB2 pathways.

  16. Functional expression of a single-chain antibody to ErbB-2 in plants and cell-free systems

    Directory of Open Access Journals (Sweden)

    Benevolo Maria

    2006-09-01

    Full Text Available Abstract Background Aberrant signaling by ErbB-2 (HER 2, Neu, a member of the human Epidermal Growth Factor (EGF receptor family, is associated with an aggressive clinical behaviour of carcinomas, particularly breast tumors. Antibodies targeting the ErbB-2 pathway are a preferred therapeutic option for patients with advanced breast cancer, but a worldwide deficit in the manufacturing capacities of mammalian cell bioreactors is foreseen. Methods Herein, we describe a multi-platform approach for the production of recombinant Single chain Fragments of antibody variable regions (ScFvs to ErbB-2 that involves their functional expression in (a bacteria, (b transient as well as stable transgenic tobacco plants, and (c a newly developed cell-free transcription-translation system. Results An ScFv (ScFv800E6 was selected by cloning immunoglobulin sequences from murine hybridomas, and was expressed and fully functional in all the expression platforms, thereby representing the first ScFv to ErbB-2 produced in hosts other than bacteria and yeast. ScFv800E6 was optimized with respect to redox synthesis conditions. Different tags were introduced flanking the ScFv800E6 backbone, with and without spacer arms, including a novel Strep II tag that outperforms conventional streptavidin-based detection systems. ScFv800E6 was resistant to standard chemical radiolabeling procedures (i.e. Chloramine T, displayed a binding ability extremely similar to that of the parental monovalent Fab' fragment, as well as a flow cytometry performance and an equilibrium binding affinity (Ka approximately 2 × 108 M-1 only slightly lower than those of the parental bivalent antibody, suggesting that its binding site is conserved as compared to that of the parental antibody molecule. ScFv800E6 was found to be compatible with routine reagents for immunohistochemical staining. Conclusion ScFv800E6 is a useful reagent for in vitro biochemical and immunodiagnostic applications in oncology, and a candidate for future in vivo studies.

  17. The Role of the Rab Coupling Protein in ErbB2-Driven Mammary Tumorigenesis and Metastasis

    Science.gov (United States)

    2015-10-01

    of the Rab Coupling Protein (RCP) in ErbB2- mediated lung metastasis formation. To accomplish this, we have derived both proficient and deficient...Rab Coupling Protein (RCP), which acts as an effector for Rab11 and Rab25, mediates recycling of the EGFR/α5β1-integrin complex to plasma membrane, a...implicating RCP in cancer progression. For example, RCP- mediated recycling of the integrin 51 is activated by expression of mutant forms of p53 resulting

  18. HER2/ErbB2 receptor signaling in rat and human prolactinoma cells: strategy for targeted prolactinoma therapy.

    Science.gov (United States)

    Fukuoka, Hidenori; Cooper, Odelia; Mizutani, Jun; Tong, Yunguang; Ren, Song-Guang; Bannykh, Serguei; Melmed, Shlomo

    2011-01-01

    Dopamine agonist resistance or intolerance is encountered in approximately 20% of prolactinoma patients. Because human epidermal growth factor receptor 2 (HER2)/ErbB2 is overexpressed in prolactinomas and ErbB receptor ligands regulate prolactin (PRL) gene expression, we tested the role of HER2/ErbB2 in prolactinoma hormone regulation and adenoma cell proliferation to assess the rationale for targeting this receptor for prolactinoma therapy. As we showed prolactinoma HER2 overexpression, we generated constitutively active HER2-stable GH3 cell transfectants (HER2CA). PRL mRNA levels were induced approximately 250-fold and PRL secretion was enhanced 100-fold in HER2CA cells, which also exhibited increased proliferation. Lapatinib, a dual tyrosine kinase inhibitor (TKI) of both epidermal growth factor receptor (EGFR)/ErbB1 and HER2, blocked receptor signaling, and suppressed PRL expression more than gefitinib, a TKI of EGFR/ErbB1. Lapatinib also suppressed colony formation in soft agar more than gefitinib. Oral lapatinib treatment caused tumor shrinkage and serum PRL suppression both in HER2CA transfectant-inoculated Wistar-Furth rats and in estrogen-induced Fischer344 rat prolactinomas. In cultured human cells derived from resected prolactinoma tissue, lapatinib suppressed both PRL mRNA expression and secretion. These results demonstrate that prolactinoma HER2 potently induces PRL and regulates experimental prolactinoma cell proliferation. Because pituitary HER2 signaling is abrogated by TKIs, this receptor could be an effective target for prolactinoma therapy.

  19. Specific targeted killing of ErbB2 positive breast cancer by retrovirus-mediated Immunocaspase-3 secreting T cells

    Institute of Scientific and Technical Information of China (English)

    ZHANG Lihong; YANG An-gang; JIA Lintao; ZHAO Jing; XU Yanming; WEN Weihong; BAO Wei; CAO Yunxin; SU Chengzhi; WANG Chengji

    2004-01-01

    In this study, Immunocaspase-3 gene was transfected into Jurkat T lymphocytes and the targeted proapoptotic protein Immunocaspase-3 was stably secreted.Its entry to ErbB2 positive SKBr3 breast carcinoma cell line was observed by indirect immunofluorescence staining.Growth of SKBr3 cells was significantly inhibited when they were cultured with medium containing Immunocaspase-3.Next, Immunocaspase-3 gene was cloned into retrovirus vector pLNCX, which was then transfected into PA317 cells to package. Packaged cells producing high titer pseudoviruses were acquired and the pseudoviruses were harvested to infect PBMCs, which had been stimulated to division. The latter were selected and administered to nude mice bearing SKBr3 tumors through tail vein. The results showed that the treatment contributed to an inhibition of tumor growth and prolonged the lifetime of nude mice bearing SKBr3 tumor.The efficiency of inhibition of tumor reached 73.25%, and the average lifetime of treated nude mice was 80.95% longer than that of control group. Immunohistochemical examination revealed the exclusive distribution of Immunocaspase-3proteins only in the tumor tissue samples; and TUNEL assay confirmed the occurrence of apoptosis in tumor cells. The present study suggests that Immunocaspase-3 secreted by T lymphocytes can selectively bind and enter into ErbB2 positive breast cancer cells, where it exhibits a proapoptotic activity and causes tumor suppression in an in vivo tumor model.

  20. ErbB2 and ErbB3 regulate amputation-induced proliferation and migration during vertebrate regeneration.

    Science.gov (United States)

    Rojas-Muñoz, Agustin; Rajadhyksha, Shibani; Gilmour, Darren; van Bebber, Frauke; Antos, Christopher; Rodríguez Esteban, Concepción; Nüsslein-Volhard, Christiane; Izpisúa Belmonte, Juan Carlos

    2009-03-01

    Epimorphic regeneration is a unique and complex instance of postembryonic growth observed in certain metazoans that is usually triggered by severe injury [Akimenko et al., 2003; Alvarado and Tsonis, 2006; Brockes, 1997; Endo et al., 2004]. Cell division and migration are two fundamental biological processes required for supplying replacement cells during regeneration [Endo et al., 2004; Slack, 2007]. However, the connection between the early stimuli generated after injury and the signals regulating proliferation and migration during regeneration remain largely unknown. Here we show that the oncogenes ErbB2 and ErbB3, two members of the EGFR family, are essential for mounting a successful regeneration response in vertebrates. Importantly, amputation-induced progenitor proliferation and migration are significantly reduced upon genetic and/or chemical modulation of ErbB function. Moreover, we also found that NRG1 and PI3K functionally interact with ErbB2 and ErbB3 during regeneration and interfering with their function also abrogates the capacity of progenitor cells to regenerate lost structures upon amputation. Our findings suggest that ErbB, PI3K and NRG1 are components of a permissive switch for migration and proliferation continuously acting across the amputated fin from early stages of vertebrate regeneration onwards that regulate the expression of the transcription factors lef1 and msxB.

  1. Screening to Identify Commonly Used Chinese Herbs That Affect ERBB2 and ESR1 Gene Expression Using the Human Breast Cancer MCF-7 Cell Line

    Directory of Open Access Journals (Sweden)

    Jen-Hwey Chiu

    2014-01-01

    Full Text Available Aim. Our aim the was to screen the commonly used Chinese herbs in order to detect changes in ERBB2 and ESR1 gene expression using MCF-7 cells. Methods. Using the MCF-7 human breast cancer cell line, cell cytotoxicity and proliferation were evaluated by MTT and trypan blue exclusion assays, respectively. A luciferase reporter assay was established by transient transfecting MCF-7 cells with plasmids containing either the ERBB2 or the ESR1 promoter region linked to the luciferase gene. Chinese herbal extracts were used to treat the cells at 24 h after transfection, followed by measurement of their luciferase activity. The screening results were verified by Western blotting to measure HER2 and ERα protein expression. Results. At concentrations that induced little cytotoxicity, thirteen single herbal extracts and five compound recipes were found to increase either ERBB2 or ESR1 luciferase activity. By Western blotting, Si-Wu-Tang, Kuan-Shin-Yin, and Suan-Tsao-Ren-Tang were found to increase either HER2 or ERα protein expression. In addition, Ligusticum chuanxiong was shown to have a great effect on ERBB2 gene expression and synergistically with estrogen to stimulate MCF-7 cell growth. Conclusion. Our results provide important information that should affect clinical treatment strategies among breast cancer patients who are receiving hormonal or targeted therapies.

  2. Prolyl isomerase Pin1 is highly expressed in Her2-positive breast cancer and regulates erbB2 protein stability

    Directory of Open Access Journals (Sweden)

    Lu Kun

    2008-12-01

    Full Text Available Abstract Overexpression of HER-2/Neu occurs in about 25–30% of breast cancer patients and is indicative of poor prognosis. While Her2/Neu overexpression is primarily a result of erbB2 amplification, it has recently been recognized that erbB2 levels are also regulated on the protein level. However, factors that regulate Her2/Neu protein stability are less well understood. The prolyl isomerase Pin1 catalyzes the isomerization of specific pSer/Thr-Pro motifs that have been phosphorylated in response to mitogenic signaling. We have previously reported that Pin1-catalyzed post-phosphorylational modification of signal transduction modulates the oncogenic pathways downstream from c-neu. The goal of this study was to examine the expression of prolyl isomerase Pin1 in human Her2+ breast cancer, and to study if Pin1 affects the expression of Her2/Neu itself. Methods Immunohistochemistry for Her2 and Pin1 were performed on two hundred twenty-three human breast cancers, with 59% of the specimen from primary cancers and 41% from metastatic sites. Pin1 inhibition was achieved using siRNA in Her2+ breast cancer cell lines, and its effects were studied using cell viability assays, immunoblotting and immunofluorescence. Results Sixty-four samples (28.7% stained positive for Her2 (IHC 3+, and 54% (122/223 of all breast cancers stained positive for Pin1. Of the Her2-positive cancers 40 (62.5% were also Pin1-positive, based on strong nuclear or nuclear and cytoplasmic staining. Inhibition of Pin1 via RNAi resulted in significant suppression of Her2-positive tumor cell growth in BT474, SKBR3 and AU565 cells. Pin1 inhibition greatly increased the sensitivity of Her2-positive breast cancer cells to the mTOR inhibitor Rapamycin, while it did not increase their sensitivity to Trastuzumab, suggesting that Pin1 might act on Her2 signaling. We found that Pin1 interacted with the protein complex that contains ubiquitinated erbB2 and that Pin1 inhibition accelerated erbB2 degradation, which could be prevented by treatments with the proteasome inhibitor ALLnL. Conclusion Pin1 is a novel regulator of erbB2 that modulates the ubiquitin-mediated degradation of erbB2. The overexpression of Pin1 in a majority of Her2-overexpressing breast cancer may contribute to maintain erbB2 levels. Pin1 inhibition alone and in conjunction with mTOR inhibition suppresses the growth of Her2+ breast cancer cells.

  3. Intermittent hypoxia induces the proliferation of rat vascular smooth muscle cell with the increases in epidermal growth factor family and erbB2 receptor

    Energy Technology Data Exchange (ETDEWEB)

    Kyotani, Yoji, E-mail: cd147@naramed-u.ac.jp [Department of Pharmacology, Nara Medical University School of Medicine, Kashihara 634-8521 (Japan); Department of Pharmacy, Nara Medical University Hospital, Kashihara 634-8522 (Japan); Ota, Hiroyo [Second Department of Internal Medicine, Nara Medical University School of Medicine, Kashihara 634-8522 (Japan); Department of Biochemistry, Nara Medical University School of Medicine, Kashihara 634-8521 (Japan); Itaya-Hironaka, Asako; Yamauchi, Akiyo; Sakuramoto-Tsuchida, Sumiyo [Department of Biochemistry, Nara Medical University School of Medicine, Kashihara 634-8521 (Japan); Zhao, Jing; Ozawa, Kentaro; Nagayama, Kosuke; Ito, Satoyasu [Department of Pharmacology, Nara Medical University School of Medicine, Kashihara 634-8521 (Japan); Takasawa, Shin [Department of Biochemistry, Nara Medical University School of Medicine, Kashihara 634-8521 (Japan); Kimura, Hiroshi [Second Department of Internal Medicine, Nara Medical University School of Medicine, Kashihara 634-8522 (Japan); Uno, Masayuki [Department of Pharmacy, Nara Medical University Hospital, Kashihara 634-8522 (Japan); Yoshizumi, Masanori [Department of Pharmacology, Nara Medical University School of Medicine, Kashihara 634-8521 (Japan)

    2013-11-15

    Obstructive sleep apnea is characterized by intermittent hypoxia (IH), and associated with cardiovascular diseases, such as stroke and heart failure. These cardiovascular diseases have a relation to atherosclerosis marked by the proliferation of vascular smooth muscle cells (VSMCs). In this study, we investigated the influence of IH on cultured rat aortic smooth muscle cell (RASMC). The proliferation of RASMC was significantly increased by IH without changing the level of apoptosis. In order to see what induces RASMC proliferation, we investigated the influence of normoxia (N)-, IH- and sustained hypoxia (SH)-treated cell conditioned media on RASMC proliferation. IH-treated cell conditioned medium significantly increased RASMC proliferation compared with N-treated cell conditioned medium, but SH-treated cell conditioned medium did not. We next investigated the epidermal growth factor (EGF) family as autocrine growth factors. Among the EGF family, we found significant increases in mRNAs for epiregulin (ER), amphiregulin (AR) and neuregulin-1 (NRG1) in IH-treated cells and mature ER in IH-treated cell conditioned medium. We next investigated the changes in erbB family receptors that are receptors for ER, AR and NRG1, and found that erbB2 receptor mRNA and protein expressions were increased by IH, but not by SH. Phosphorylation of erbB2 receptor at Tyr-1248 that mediates intracellular signaling for several physiological effects including cell proliferation was increased by IH, but not by SH. In addition, inhibitor for erbB2 receptor suppressed IH-induced cell proliferation. These results provide the first demonstration that IH induces VSMC proliferation, and suggest that EGF family, such as ER, AR and NRG1, and erbB2 receptor could be involved in the IH-induced VSMC proliferation. - Highlights: ●In vitro system for intermittent hypoxia (IH) and sustained hypoxia (SH). ●IH, but not SH, induces the proliferation of rat vascular smooth muscle cell. ●Epiregulin mRNA and protein are up-regulated in IH, but not in SH. ●IH-induced erbB2 phosphorylation is attenuated by erbB2 inhibitor. ●EGF family and erbB2 receptor may be involved in IH-induced cell proliferation.

  4. Sequence Variants and Haplotype Analysis of Cat ERBB2 Gene: A Survey on Spontaneous Cat Mammary Neoplastic and Non-Neoplastic Lesions

    Science.gov (United States)

    Santos, Sara; Bastos, Estela; Baptista, Cláudia S.; Sá, Daniela; Caloustian, Christophe; Guedes-Pinto, Henrique; Gärtner, Fátima; Gut, Ivo G.; Chaves, Raquel

    2012-01-01

    The human ERBB2 proto-oncogene is widely considered a key gene involved in human breast cancer onset and progression. Among spontaneous tumors, mammary tumors are the most frequent cause of cancer death in cats and second most frequent in humans. In fact, naturally occurring tumors in domestic animals, more particularly cat mammary tumors, have been proposed as a good model for human breast cancer, but critical genetic and molecular information is still scarce. The aims of this study include the analysis of the cat ERBB2 gene partial sequences (between exon 17 and 20) in order to characterize a normal and a mammary lesion heterogeneous populations. Cat genomic DNA was extracted from normal frozen samples (n = 16) and from frozen and formalin-fixed paraffin-embedded mammary lesion samples (n = 41). We amplified and sequenced two cat ERBB2 DNA fragments comprising exons 17 to 20. It was possible to identify five sequence variants and six haplotypes in the total population. Two sequence variants and two haplotypes show to be specific for cat mammary tumor samples. Bioinformatics analysis predicts that four of the sequence variants can produce alternative transcripts or activate cryptic splicing sites. Also, a possible association was identified between clinicopathological traits and the variant haplotypes. As far as we know, this is the first attempt to examine ERBB2 genetic variations in cat mammary genome and its possible association with the onset and progression of cat mammary tumors. The demonstration of a possible association between primary tumor size (one of the two most important prognostic factors) and the number of masses with the cat ERBB2 variant haplotypes reveal the importance of the analysis of this gene in veterinary medicine. PMID:22489125

  5. ESR1, ERBB2, and Ki67 mRNA expression predicts stage and grade of non-muscle-invasive bladder carcinoma (NMIBC).

    Science.gov (United States)

    Breyer, Johannes; Wirtz, Ralph M; Laible, Mark; Schlombs, Kornelia; Erben, Philipp; Kriegmair, Maximilian Christian; Stoehr, Robert; Eidt, Sebastian; Denzinger, Stefan; Burger, Maximilian; Hartmann, Arndt; Otto, Wolfgang

    2016-11-01

    Pathological staging and grading are crucial for risk assessment in non-muscle-invasive bladder cancer (NMIBC). Molecular grading might support pathological evaluation and minimize interobserver variability. In this study, the well-established breast cancer markers ESR1, PGR, ERBB2, and MKI67 were evaluated as potential molecular markers to support grading and staging in NMIBC. We retrospectively analyzed clinical data and formalin-fixed paraffin-embedded tissues (FFPE) of patients with NMIBC. Messenger RNA (mRNA) expression of the aforementioned markers was measured by single-step reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) using RNA-specific TaqMan assays. Relative gene expression was determined by normalization to two reference genes (CALM2 and B2M) using the 40(-ΔΔCT) method and correlated to histopathological stage and grade. Pathological assessment was performed by an experienced uropathologist. Statistical analysis was performed using the SAS software JMP 9.0.0 version and GraphPad Prism 5.04. Of 381 cases of NMIBC, samples of 100 pTa and 255 pT1 cases were included in the final study. Spearman rank correlation revealed significant correlations between grade and expression of MKI67 (r = 0.52, p < 0.0001), ESR1 (r = 0.25, p < 0.0001), and ERBB2 (r = 0.18, p = 0.0008). In Mann-Whitney tests, MKI67 was significantly different between all grades (p < 0.0001), while ESR1 (p = 0.0006) and ERBB2 (p = 0.027) were significantly different between G2 and G3. Higher expression of MKI67 (r = 0.49; p < 0.0001), ERBB2 (r = 0.22; p < 0.0001), and ESR1 (r = 0.18; p = 0.0009) mRNA was positively correlated with higher stage. MKI67 (p < 0.0001), ERBB2 (p = 0.0058), and PGR (p = 0.0007) were significantly different between pTa and pT1. In NMIBC expression of ESR1, ERBB2 and MKI67 are significantly different between stage and grade. This potentially provides objective parameters for pathological

  6. Ligand-associated ERBB2/3 activation confers acquired resistance to FGFR inhibition in FGFR3-dependent cancer cells.

    Science.gov (United States)

    Wang, J; Mikse, O; Liao, R G; Li, Y; Tan, L; Janne, P A; Gray, N S; Wong, K-k; Hammerman, P S

    2015-04-23

    Somatic alterations of fibroblast growth factor receptors (FGFRs) have been described in a wide range of malignancies. A number of anti-FGFR therapies are currently under investigation in clinical trials for subjects with FGFR gene amplifications, mutations and translocations. Here, we develop cell line models of acquired resistance to FGFR inhibition by exposure of cell lines harboring FGFR3 gene amplification and translocation to the selective FGFR inhibitor BGJ398 and multitargeted FGFR inhibitor ponatinib. We show that the acquisition of resistance is rapid, reversible and characterized by an epithelial to mesenchymal transition and a switch from dependency on FGFR3 to ERBB family members. Acquired resistance was associated with demonstrable changes in gene expression including increased production of ERBB2/3 ligands, which were sufficient to drive resistance in the setting of FGFR3 dependency but not dependency on other FGFR family members. These data support the concept that activation of ERBB family members is sufficient to bypass dependency on FGFR3 and suggest that concurrent inhibition of these two pathways may be desirable when targeting FGFR3-dependent cancers.

  7. Truncated ErbB2 receptor enhances ErbB1 signaling and induces reversible, ERK-independent loss of epithelial morphology

    DEFF Research Database (Denmark)

    Egeblad, M; Mortensen, Ole Hartvig; Jäättelä, M

    2001-01-01

    breast cancer cells expressing NH(2)-terminally truncated ErbB2 (DeltaNErbB2) were compared with cells overexpressing wild-type ErbB2. Expression of DeltaNErbB2 in MCF-7 cells resulted in sustained activation of extracellular signal-regulated kinases (ERK) 1/2, extensive loss of the epithelial morphology...... and depended on continuous expression of DeltaNErbB2 but not on the activation of the ERK1/2 pathway. Interestingly, the expression of DeltaNErbB2 resulted also in the increased expression and phosphorylation of ErbB1 as well as in the prolonged ligand-induced activation of the ErbB1 signaling pathway...

  8. Topoisomerase II alpha gene copy loss has adverse prognostic significance in ERBB2-amplified breast cancer: a retrospective study of paraffin-embedded tumor specimens and medical charts

    Directory of Open Access Journals (Sweden)

    Zhu April

    2008-08-01

    Full Text Available Abstract Background Amplification of the ERBB2 (Her-2/neu oncogene, which occurs in approximately 25% of breast carcinomas, is a known negative prognostic factor. Available data indicate that a variable number of nearby genes on chromosome 17q may be co-amplified or deleted, forming a continuous amplicon of variable size. In approximately 25% of these patients, the amplicon extends to the gene for topoisomerase II alpha (TOP2A, a target for anthracyclines. We sought to understand the significance of these associated genomic changes for breast cancer prognosis and predicting response to therapy. Methods and patients Archival tissue samples from 63 breast cancer patients with ERBB2 amplification, stages 0–IV, were previously analyzed with FISH probes for genes located near ERBB2. In the present study, the clinical outcome data were determined for all patients presenting at stages I–III for whom adequate clinical follow up was available. Results Four amplicon patterns (Classes were identified. These were significantly associated with the clinical outcome, specifically, recurrence of breast cancer. The Amplicon class IV with deleted TOP2A had 67% (6/9 cases with recurrence, whereas the other three classes combined had only 12% (3/25 cases (p-value = 0.004 at the time of last follow-up. TOP2A deletion was also significantly associated with time to recurrence (p-value = 0.0002. After adjusting for age in Cox regression analysis, the association between TOP2A deletion and time to recurrence remains strongly significant (p-value = 0.002 whereas the association with survival is marginally significant (p-value = 0.06. Conclusion TOP2A deletion is associated with poor prognosis in ERBB2-amplified breast carcinomas. Clarification of the mechanism of this association will require additional study.

  9. tabAnti-HER2 (erbB-2 oncogene effects of phenolic compounds directly isolated from commercial Extra-Virgin Olive Oil (EVOO

    Directory of Open Access Journals (Sweden)

    Carrasco-Pancorbo Alegria

    2008-12-01

    Full Text Available Abstract Background The effects of the olive oil-rich Mediterranean diet on breast cancer risk might be underestimated when HER2 (ERBB2 oncogene-positive and HER2-negative breast carcinomas are considered together. We here investigated the anti-HER2 effects of phenolic fractions directly extracted from Extra Virgin Olive Oil (EVOO in cultured human breast cancer cell lines. Methods Solid phase extraction followed by semi-preparative high-performance liquid chromatography (HPLC was used to isolate phenolic fractions from commercial EVOO. Analytical capillary electrophoresis coupled to mass spectrometry was performed to check for the composition and to confirm the identity of the isolated fractions. EVOO polyphenolic fractions were tested on their tumoricidal ability against HER2-negative and HER2-positive breast cancer in vitro models using MTT, crystal violet staining, and Cell Death ELISA assays. The effects of EVOO polyphenolic fractions on the expression and activation status of HER2 oncoprotein were evaluated using HER2-specific ELISAs and immunoblotting procedures, respectively. Results Among the fractions mainly containing the single phenols hydroxytyrosol and tyrosol, the polyphenol acid elenolic acid, the lignans (+-pinoresinol and 1-(+-acetoxypinoresinol, and the secoiridoids deacetoxy oleuropein aglycone, ligstroside aglycone, and oleuropein aglycone, all the major EVOO polyphenols (i.e. secoiridoids and lignans were found to induce strong tumoricidal effects within a micromolar range by selectively triggering high levels of apoptotic cell death in HER2-overexpressors. Small interfering RNA-induced depletion of HER2 protein and lapatinib-induced blockade of HER2 tyrosine kinase activity both significantly prevented EVOO polyphenols-induced cytotoxicity. EVOO polyphenols drastically depleted HER2 protein and reduced HER2 tyrosine autophosphorylation in a dose- and time-dependent manner. EVOO polyphenols-induced HER2 downregulation

  10. Naked Polyamidoamine Polymers Intrinsically Inhibit Angiotensin II-Mediated EGFR and ErbB2 Transactivation in a Dendrimer Generation- and Surface Chemistry-Dependent Manner.

    Science.gov (United States)

    Akhtar, Saghir; El-Hashim, Ahmed Z; Chandrasekhar, Bindu; Attur, Sreeja; Benter, Ibrahim F

    2016-05-01

    The effects of naked polyamidoamine (PAMAM) dendrimers on renin-angiotensin system (RAS) signaling via Angiotensin (Ang) II-mediated transactivation of the epidermal growth factor receptor (EGFR) and the closely related family member ErbB2 (HER2) were investigated. In primary aortic vascular smooth muscle cells, a cationic fifth-generation (G5) PAMAM dendrimer dose- and time-dependently inhibited Ang II/AT1 receptor-mediated transactivation of EGFR and ErbB2 as well as their downstream signaling via extracellular-regulated kinase 1/2 (ERK1/2). Inhibition even occurred at noncytotoxic concentrations at short (1 h) exposure times and was dependent on dendrimer generation (G7 > G6 > G5 > G4) and surface group chemistry (amino > carboxyl > hydroxyl). Mechanistically, the cationic G5 PAMAM dendrimer inhibited Ang II-mediated transactivation of EGFR and ErbB2 via inhibition of the nonreceptor tyrosine kinase Src. This novel, early onset, intrinsic biological action of PAMAM dendrimers as inhibitors of the Ang II/AT1/Src/EGFR-ErbB2/ERK1/2 signaling pathway could have important toxicological and pharmacological implications.

  11. ErbB2 and NFκB overexpression as predictors of chemoradiation resistance and putative targets to overcome resistance in muscle-invasive bladder cancer.

    Directory of Open Access Journals (Sweden)

    Fumitaka Koga

    Full Text Available Radical cystectomy for muscle-invasive bladder cancer (MIBC patients frequently impairs their quality of life (QOL due to urinary diversion. To improve their QOL, a bladder-sparing alternative strategy using chemoradiation has been developed. In bladder-sparing protocols, complete response (CR to induction chemoradiation is a prerequisite for bladder preservation and favorable survival. Thus predicting chemoradiation resistance and overcoming it would increase individual MIBC patients' chances of bladder preservation. The aim of this study is to investigate putative molecular targets for treatment aimed at improving chemoradiation response. Expression levels of erbB2, NFκB, p53, and survivin were evaluated immunohistochemically in pretreatment biopsy samples from 35 MIBC patients in whom chemoradiation sensitivity had been pathologically evaluated in cystectomy specimens, and associations of these expression levels with chemoradiation sensitivity and cancer-specific survival (CSS were investigated. Of the 35 patients, 11 (31% achieved pathological CR, while tumors in the remaining 24 patients (69% were chemoradiation-resistant. Multivariate analysis identified erbB2 and NFκB overexpression and hydronephrosis as significant and independent risk factors for chemoradiation resistance with respective relative risks of 11.8 (P = 0.014, 15.4 (P = 0.024 and 14.3 (P = 0.038. The chemoradiation resistance rate was 88.5% for tumors overexpressing erbB2 and/or NFκB, but only 11.1% for those negative for both (P <0.0001. The 5-year CSS rate was 74% overall. Through multivariate analysis, overexpression of erbB2 and/or NFκB was identified as an independent risk factor for bladder cancer death with marginal significance (hazard ratio 21.5, P = 0.056 along with chemoradiation resistance (P = 0.003 and hydronephrosis (P = 0.018. The 5-year CSS rate for the 11 patients achieving pathological CR was 100%, while that for the 24 with chemoradiation-resistant disease was 61% (P = 0.018. Thus, erbB2 and NFκB overexpression are relevant to chemoradiation resistance and are putative targets aimed at overcoming chemoradiation resistance in MIBC.

  12. Significance of ERBB2 Overexpression in Therapeutic Resistance and Cancer-Specific Survival in Muscle-Invasive Bladder Cancer Patients Treated With Chemoradiation-Based Selective Bladder-Sparing Approach

    Energy Technology Data Exchange (ETDEWEB)

    Inoue, Masaharu [Department of Urology, Tokyo Medical and Dental University, Graduate School, Tokyo (Japan); Koga, Fumitaka, E-mail: f-koga@cick.jp [Department of Urology, Tokyo Medical and Dental University, Graduate School, Tokyo (Japan); Yoshida, Soichiro [Department of Urology, Tokyo Medical and Dental University, Graduate School, Tokyo (Japan); Tamura, Tomoki [Department of Pathology, Tokyo Medical and Dental University, Graduate School, Tokyo (Japan); Fujii, Yasuhisa [Department of Urology, Tokyo Medical and Dental University, Graduate School, Tokyo (Japan); Ito, Eisaku [Department of Pathology, Tokyo Medical and Dental University, Graduate School, Tokyo (Japan); Kihara, Kazunori [Department of Urology, Tokyo Medical and Dental University, Graduate School, Tokyo (Japan)

    2014-10-01

    Purpose: To investigate the associations of ERBB 2 overexpression with chemoradiation therapy (CRT) resistance and cancer-specific survival (CSS) in muscle-invasive bladder cancer (MIBC) patients treated with the CRT-based bladder-sparing protocol. Methods and Materials: From 1997 to 2012, 201 patients with cT2-4aN0M0 bladder cancer were treated with CRT (40 Gy with concurrent cisplatin) following transurethral resection of bladder tumor (TURBT). Basically, patients with tumors that showed good CRT response and were amenable to segmental resection underwent partial cystectomy (PC) with pelvic lymph node dissection for bladder preservation; otherwise, radical cystectomy (RC) was recommended. Included in this study were 119 patients in whom TURBT specimens were available for immunohistochemical analysis of ERBB 2 expression. Following CRT, 30 and 65 patients underwent PC or RC, respectively; the remaining 24 patients did not undergo cystectomy. Tumors were defined as CRT-resistant when patients did not achieve complete response after CRT. Associations of ERBB 2 overexpression with CRT resistance and CSS were evaluated. Results: CRT resistance was observed clinically in 56% (67 of 119 patients) and pathologically (in cystectomy specimens) in 55% (52 of 95 patients). ERBB 2 overexpression was observed in 45 patients (38%). On multivariate analysis, ERBB 2 overexpression was an independent predictor for CRT resistance clinically (odds ratio, 3.6; P=.002) and pathologically (odds ratio, 2.9; P=.031). ERBB 2 overexpression was associated with shorter CSS (5-year CSS rates, 56% vs 87% for the ERBB 2 overexpression group vs the others; P=.001). ERBB 2 overexpression was also an independent risk factor for bladder cancer death at all time points of our bladder-sparing protocol (pre-CRT, post-CRT, and post-cystectomy). Conclusions: ERBB 2 overexpression appears relevant to CRT resistance and unfavorable CSS in MIBC patients treated with the CRT-based bladder

  13. Comparative oncology: ErbB-1 and ErbB-2 homologues in canine cancer are susceptible to cetuximab and trastuzumab targeting

    Science.gov (United States)

    Singer, Josef; Weichselbaumer, Marlene; Stockner, Thomas; Mechtcheriakova, Diana; Sobanov, Yury; Bajna, Erika; Wrba, Friedrich; Horvat, Reinhard; Thalhammer, Johann G.; Willmann, Michael; Jensen-Jarolim, Erika

    2012-01-01

    To facilitate comparative oncology trials we compared the biological and molecular homologies of canine (dog; Canis lupus familiaris) and human tumor-associated antigens ErbB-1 and -2. Further, we investigated whether they could serve as targets for anti-ErbB-1 (cetuximab) and anti-ErbB-2 antibodies (trastuzumab), which are highly relevant in human clinical oncology. Immunohistochemistry of canine mammary cancer showed ErbB-1 overexpression in 3/10 patients and ErbB-2 in 4/10. We report 91% amino acid homology for ErbB-1 and 92% for ErbB-2 between canine and human molecules. Modeling of canine on human ErbB-1 revealed that the cetuximab epitope only differs by 4 amino acids: Lys443 is replaced by Arg, Ser468 by Asn, Gly471 by Asp, and Asn473 by Lys in canines. The trastuzumab binding site is identical in human and canine ErbB-2 apart from a single amino acid change (Pro557 to Ser). Binding of cetuximab and trastuzumab to canine mammary carcinoma cells CF33, CF41, Sh1b and P114 was confirmed by flow cytometry. Both antibodies significantly inhibited canine tumor cell proliferation partly due to growth arrest in G0/G1 phase. We explain the lower efficiency on the tested canine than on human SKBR3 and A431 cells, by a 2-log lower expression level of the canine ErbB-1 and -2 molecules. Our results indicate significant homology of human and canine Erb-1 and -2 tumor associated antigens. The fact that the canine homologues express the cetuximab and trastuzumab epitopes may facilitate antibody-based immunotherapy in dogs. Importantly, the striking similarities of ErbB-1 and -2 molecules open up avenues towards comparative strategies for targeted drug development. PMID:22424313

  14. 抗p185erbB2人鼠嵌合抗体慢病毒表达载体的构建%Construction of the Lentiviral Expression Vector for Anti-p185erbB2 Mouse/Human Chimeric Antibody

    Institute of Scientific and Technical Information of China (English)

    刘芳; 李力; 张玮; 王琪

    2013-01-01

    本研究构建抗p185erbB2人鼠嵌合抗体慢病毒表达载体,并将其转染293T细胞,明确转染后嵌合抗体基因的表达情况.采用PCR法扩增抗p185erbB2鼠单抗轻、重链可变区基因(vL和vH)和人IgG1的轻、重链恒定区基因(κ和γ1),再利用三引物PCR法将vL和κ,vH和γ1进行拼接,得到嵌合轻链基因(L)和嵌合重链基因(H),分别插入质粒pVAX1/IRES的IRES元件的下、上游.用内切酶将H-IRES-L从pVAX1/H-IRES-L上切下,插入慢病毒载体pWPI中,经相应酶切和测序鉴定,正确构建了慢病毒表达载体pWPI/H-IRES-L.将其转染293T细胞,48 h后通过荧光显微镜检测绿色荧光蛋白(GFP)的表达,RT-PCR和直接ELISA法检测嵌合抗体的表达.结果显示,转染pWPI/H-IRES-L的293T细胞中有嵌合轻链和嵌合重链基因的共同表达,而且表达的嵌合抗体能够与p185erbB2分子特异性结合,为今后抗p185erbB2工程抗体的研究奠定了基础.%This research was to construct the lentiviral expression vector for anti- pl85erbB2 mouse/human chimeric antibody and to determine the expression of the chimeric antibody gene in 293T cells transfected with this vector. The genes (vL and vH) coding light and heavy chain of variable regions of anti-pl85erbB2 mAb and the constant regions of human IgG1 (Κ and γ1) were cloned with PCR method. The target genes were assembled by three-primers PCR method to obtain the chimeric light chain (L) and the chimeric heavy chain (H). Both chains inserted into the down stream and upper stream of IRES gene of the plasmid pVAX1/IRES respectively. We digested the plasmid pVAX1/ H-IRES-L with endoenzyme and subcloned H-IRES-L into the lentiviral vector pWPI. The enzyme digestion and sequence analysis showed that the lentiviral expression vector pWPI/H-IRES-L was constructed correctly. Then, it was transfected into 293T cells and after 48h, GFP protein expression in 293T cells were detected by fluorescent microscope and the chimeric antibody expression was detected by RT-PCR and direct ELISA. The results showed that after 293T cells were transfected with recombination plasmid, both light and heavy chains of the chimeric antibody genes could express together. The chimeric antibody expressed could bind to pl85erbB2 specifically. This research may lay a sound foundation for further study of anti-pl85erbB2engineered antibody.

  15. Label-Free Quantitation and Mapping of the ErbB2 Tumor Receptor by Multiple Protease Digestion with Data-Dependent (MS1 and Data-Independent (MS2 Acquisitions

    Directory of Open Access Journals (Sweden)

    Jason M. Held

    2013-01-01

    Full Text Available The receptor tyrosine kinase ErbB2 is a breast cancer biomarker whose posttranslational modifications (PTMs are a key indicator of its activation. Quantifying the expression and PTMs of biomarkers such as ErbB2 by selected reaction monitoring (SRM mass spectrometry has several limitations, including minimal coverage and extensive assay development time. Therefore, we assessed the utility of two high resolution, full scan mass spectrometry approaches, MS1 Filtering and SWATH MS2, for targeted ErbB2 proteomics. Endogenous ErbB2 immunoprecipitated from SK-BR-3 cells was in-gel digested with trypsin, chymotrypsin, Asp-N, or trypsin plus Asp-N in triplicate. Data-dependent acquisition with an AB SCIEX TripleTOF 5600 and MS1 Filtering data processing was used to assess peptide and PTM coverage as well as the reproducibility of enzyme digestion. Data-independent acquisition (SWATH was also performed for MS2 quantitation. MS1 Filtering and SWATH MS2 allow quantitation of all detected analytes after acquisition, enabling the use of multiple proteases for quantitative assessment of target proteins. Combining high resolution proteomics with multiprotease digestion enabled quantitative mapping of ErbB2 with excellent reproducibility, improved amino acid sequence and PTM coverage, and decreased assay development time compared to typical SRM assays. These results demonstrate that high resolution quantitative proteomic approaches are an effective tool for targeted biomarker quantitation.

  16. 人脑胶质瘤中MGMT、erbB2的表达及其意义%Expression and significance of MGMT and erbB2 in human glioma

    Institute of Scientific and Technical Information of China (English)

    孙春明; 王之敏; 周幽心; 左剑玲; 许期年; 王秀英; 周岱

    2009-01-01

    Objective To study the expression and significance of MGMT and erbB2 in human glioma. Methods RT-PCR method was used to determine the mRNA levels of MGMT and erbB2 gene in 42 clinical glioma specimens. Results The expression rates of MGMT and erbB2 in human glioma were 45. 2% and 61. 9%, respectively. The expression of MGMT was closely correlated to that of erbB2 (P<0. 01). Conclusion MGMT and erbB2 are all overexpressed in human gliomas, which is helpful to the drug selection for chemotherapy.%目的 探讨脑胶质瘤组织中耐药相关基因MGMT、erbB2的表达及临床意义.方法 采用RT-PCR法对42例脑胶质瘤标本中MGMT、erbB2 mRNA进行测定.结果 MGMT和erbB2在脑胶质瘤标本中的阳性表达率分别为45.2%和61.9%,两者有极显著相关性(P<0.01).结论 MGMT和erbB2在脑胶质瘤中均有较高表达,对合理选择胶质瘤化疗药物有一定临床意义.

  17. Testing ERBB2 p.L755S kinase domain mutation as a druggable target in a patient with advanced colorectal cancer

    Science.gov (United States)

    Aung, Kyaw L.; Stockley, Tracy L.; Serra, Stefano; Kamel-Reid, Suzanne; Bedard, Philippe L.; Siu, Lillian L.

    2016-01-01

    Recent advances in molecular profiling technologies allow genetic driver events in individual tumors to be identified. The hypothesis behind this ongoing molecular profiling effort is that improvement in patients’ clinical outcomes will be achieved by inhibiting these discovered genetic driver events with matched targeted drugs. This hypothesis is currently being tested in oncology clinics with variable early results. Herein, we present our experience with a case of advanced colorectal cancer (CRC) with an ERBB2 p.L755S kinase domain mutation, a BRAF p.N581S mutation, and an APC p.Q1429fs mutation, together with a brief review of the literature describing the biological and clinical significance of ERRB2 kinase domain mutations in CRC. The patient was treated with trastuzumab combined with infusional 5-fluorouracil and leucovorin based on the presence of ERBB2 p.L755S kinase mutation in the tumor and based on the available evidence at the time when standard treatment options had been exhausted. However, there was no therapeutic response illustrating the challenges we face in managing patients with potentially targetable mutations where results from functional in vitro and in vivo studies lag behind those of genomic sequencing studies. Also lagging behind are clinical utility data from oncology clinics, hampering rapid therapeutic advances. Our case also highlights the logistical barriers associated with getting the most optimal therapeutic agents to the right patient in this era of personalized therapeutics based on cancer genomics. PMID:27626067

  18. Expression of the EGF receptor family members ErbB2, ErbB3, and ErbB4 in germinal zones of the developing brain and in neurosphere cultures containing CNS stem cells.

    Science.gov (United States)

    Kornblum, H I; Yanni, D S; Easterday, M C; Seroogy, K B

    2000-01-01

    The epidermal growth factor receptor family consists of four related tyrosine kinases: the epidermal growth factor receptor (EGF-R or ErbB), ErbB2, ErbB3, and ErbB4. These receptors are capable of extensive cross-activation upon the binding of their ligands - the EGF family of peptides for EGF-R and the neuregulins for ErbB3 and ErbB4. Since EGF-R is expressed by proliferating cells in the central nervous system (CNS), including multipotent CNS stem cells, we examined the expression of ErbB2, ErbB3 and ErbB4 in the germinal epithelia of the developing rat brain using in situ hybridization. ErbB2 and ErbB4 mRNAs were widely distributed within the germinal zones as early as E12. However, as development proceeded, ErbB2 mRNA was mainly present within the layers of cells immediately adjacent to the ventricular surface - the ventricular zone, while ErbB4 mRNA was predominantly expressed by subventricular zone cells, in the regions where these specialized germinal epithelia were present. ErbB3 mRNA distribution within germinal epithelia was more restricted, primarily confined to the diencephalon and rostral midbrain. Cultured neurospheres, which contain CNS stem cells, expressed ErbB2, ErbB4 and, to a lesser extent, ErbB3 protein as demonstrated by Western blot analysis. This expression declined during following differentiation. Heregulin-beta1, a neuregulin, had no effect on the proliferative capacity of neurospheres. Overall, our results indicate that ErbB2, ErbB3 and ErbB4 may play important and distinct roles in the genesis of the CNS. However, our in vitro data do not support a role for neuregulins in proliferation, per se, of CNS stem cells.

  19. PNA-mediated modulation and redirection of Her-2 pre-mRNA splicing: specific skipping of erbB-2 exon 19 coding for the ATP catalytic domain

    DEFF Research Database (Denmark)

    Pankratova, Stanislava; Nielsen, Birgit N; Shiraishi, Takehiko;

    2010-01-01

    The Her-2 receptor coded for by the proto-oncogenic erbB-2 gene is a clinically validated target for treatment of a significant genetic subclass of breast cancers, and Her-2 is also overexpressed or mutated in a range of other cancers. In an approach to exploit antisense mediated splicing...... oligomers that specifically induce skipping of exon 19 as this exon is coding for the ATP catalytic domain of Her-2, and if expressed such truncated version of the Her-2 protein should be functionally inactive in a dominant negative fashion. Therefore, antisense compounds having efficient erbB-2 exon 19...

  20. Gene Expression Meta-Analysis identifies Cytokine Pathways and 5q Aberrations involved in Metastasis of ERBB2 Amplified and Basal Breast Cancer

    DEFF Research Database (Denmark)

    Thomassen, Mads; Tan, Qihua; Burton, Mark

    2013-01-01

    Background: Breast tumors have been described by molecular subtypes characterized by pervasively different gene expression profiles. The subtypes are associated with different clinical parameters and origin of precursor cells. However, the biological pathways and chromosomal aberrations that differ...... the subgroups impact metastasis. Results: We have scrutinized publicly available gene expression datasets and identified molecular subtypes in 1,394 breast tumors with outcome data. By analysis of chromosomal regions and pathways using “Gene set enrichment analysis” followed by a meta-analysis, we identified...... show that high expression of 5q14 genes and low levels of TNFR2 pathway genes were associated with poor survival in basal-like cancers. Furthermore, low expression of 5q33 genes and interleukin-12 pathway genes were associated with poor outcome exclusively in ERBB2-like tumors. Conclusion...

  1. Nuclear expression of KLF6 tumor suppressor factor is highly associated with overexpression of ERBB2 oncoprotein in ductal breast carcinomas.

    Directory of Open Access Journals (Sweden)

    Ricardo C Gehrau

    Full Text Available BACKGROUND: Krüppel-like factor 6 (KLF6 is an evolutionarily conserved and ubiquitously expressed protein that belongs to the mammalian Sp1/KLF family of transcriptional regulators. Though KLF6 is a transcription factor and harbors a nuclear localization signal it is not systematically located in the nucleus but it was detected in the cytoplasm of several tissues and cell lines. Hence, it is still not fully settled whether the tumor suppressor function of KLF6 is directly associated with its ability to regulate target genes. METHODOLOGY/PRINCIPAL FINDINGS: In this study we analyzed KLF6 expression and sub-cellular distribution by immunohistochemistry in several normal and tumor tissues in a microarray format representing fifteen human organs. Results indicate that while both nuclear and cytoplasmic distribution of KLF6 is detected in normal breast tissues, breast carcinomas express KLF6 mainly detected in the cytoplasm. Expression of KLF6 was further analyzed in breast cancer tissues overexpressing ERBB2 oncoprotein, which is associated with poor disease prognosis and patient's survival. The analysis of 48 ductal carcinomas revealed a significant population expressing KLF6 predominantly in the nuclear compartment (X(2p = 0.005; Fisher p = 0.003. Moreover, this expression pattern correlates directly with early stage and small ductal breast tumors and linked to metastatic events in lymph nodes. CONCLUSIONS/SIGNIFICANCE: Data are consistent with a preferential localization of KLF6 in the nuclear compartment of early stage and small HER2-ERBB2 overexpressing ductal breast tumor cells, also presenting lymph node metastatic events. Thus, KLF6 tumor suppressor could represent a new molecular marker candidate for tumor prognosis and/or a potential target for therapy strategies.

  2. The dual targeting of EGFR and ErbB2 with the inhibitor Lapatinib corrects high glucose-induced apoptosis and vascular dysfunction by opposing multiple diabetes-induced signaling changes.

    Science.gov (United States)

    Benter, Ibrahim F; Sarkhou, Fatima; Al-Khaldi, Abeer T; Chandrasekhar, Bindu; Attur, Sreeja; Dhaunsi, Gursev S; Yousif, Mariam H M; Akhtar, Saghir

    2015-01-01

    The epidermal growth factor receptors, EGFR and EGFR2 (ErbB2), appear important mediators of diabetes-induced vascular dysfunction. We investigated whether targeted dual inhibition of EGFR and ErbB2 with Lapatinib would be effective in treating diabetes-induced vascular dysfunction in a rat model of type 1 diabetes. In streptozotocin-induced diabetes, chronic 4-week oral or acute, ex vivo, administration of Lapatinib prevented the development of vascular dysfunction as indicated by the attenuation of the hyper-reactivity of the diabetic mesenteric vascular bed (MVB) to norephinephrine without correcting hyperglycemia. Chronic in vivo or acute ex vivo Lapatinib treatment also significantly attenuated diabetes-induced increases in phosphorylation of EGFR, ErbB2, ERK1/2, AKT, ROCK2 and IkB-alpha as well as normalized the reduced levels of phosphorylated FOXO3A, and eNOS (Ser1177) in the diabetic MVB. Similar results were observed in vascular smooth muscle cells (VSMCs) cultured in high glucose (25 mM) treated with Lapatinib or small interfering RNA (siRNA) targeting the ErbB2 receptor. Lapatinib also prevented high glucose-induced apoptosis in VSMC. Thus, Lapatinib corrects hyperglycemia-induced apoptosis and vascular dysfunction with concomitant reversal of diabetes or high glucose-induced signaling changes in EGFR/ErbB2 and downstream signaling pathways implying that targeted dual inhibition of EGFR/ErbB2 might be an effective vasculoprotective treatment strategy in diabetic patients.

  3. The Na+/H+ exchanger NHE1, but not the Na+, HCO3- cotransporter NBCn1, regulates motility of MCF7 breast cancer cells expressing constitutively active ErbB2

    DEFF Research Database (Denmark)

    Lauritzen, Gitte; Stock, Christian-Martin; Lemaire, Justine;

    2012-01-01

    We and others have shown central roles of the Na(+)/H(+) exchanger NHE1 in cell motility. The aim of this study was to determine the roles of NHE1 and of the Na(+), HCO(3)(-) cotransporter NBCn1 in motility of serum-starved MCF-7 breast cancer cells expressing constitutively active ErbB2 (¿NErbB2...

  4. Early nuclear alterations and immunohistochemical expression of Ki-67, Erb-B2, vascular endothelial growth factor (VEGF), transforming growth factor (TGF-beta1) and integrine-linked kinase (ILK) two days after tamoxifen in breast carcinoma.

    Science.gov (United States)

    Morena, A M L; Oshima, C T F; Gebrim, L H; Egami, M I; Silva, M R R; Segreto, R A; Giannotti Filho, O; Teixeira, V P C; Segreto, H R C

    2004-01-01

    The purpose of the present study was to evaluate breast carcinoma samples before and two days after treatment with tamoxifen in order to analyse early histopathological alterations--particularlynuclear alterations-- as well as immunohistochemical expression of Ki-67, Erb-B2, VEGF, TGF-beta1 and ILK proteins. Twenty one cases of invasive ductal and lobular breast carcinoma were studied. Patients were submitted to biopsy of the lesion and, after confirmation of the diagnosis, they received 20 mg of tamoxifen a day, beginning two days before surgery. The samples obtained during biopsy and after surgery were stained with HE for histopathological diagnosis. Estrogen receptor was positive in 18 cases and negative in 3. The immunohistochemical method was applied for the detection of Ki-67, Erb-B2, protein, vascular endothelial growth factor (VEGF), transforming growth factor beta (TGF-beta1) and integrin linked kinase (ILK). Two days after tamoxifen treatment, the following results were observed: 1) decrease in the cell volume, chomatine condensation, nucleoli less evident and clearly defined nuclear limits; 2) significant reduction in the expression of Erb-B2 protein and significant increase in the expression of TGF-beta1 protein; 3) expression of others proteins (Ki-67, VEGF and ILK) was not altered during the indicated time frame. Our results suggest that analyzing nuclear alterations and expression of Erb-B2 and TGF-beta1 proteins would be useful to assess the initial response to tamoxifen.

  5. MGC9753 gene, located within PPP1R1B-STARD3-ERBB2-GRB7 amplicon on human chromosome 17q12, encodes the seven-transmembrane receptor with extracellular six-cystein domain.

    Science.gov (United States)

    Katoh, Masuko; Katoh, Masaru

    2003-06-01

    MYC, ERBB2, MET, FGFR2, CCNE1, MYCN, WNT2, CD44, MDM2, NCOA3, IQGAP1 and STK6 loci are amplified in human gastric cancer. It has been reported that the gene corresponding to EST H16094 is co-amplified with ERBB2 gene in human gastric cancer. Here, we identified and characterized the gene corresponding to EST H16094 by using bioinformatics. BLAST programs revealed that EST H16094 was derived from the uncharacterized MGC9753 gene. Two ORFs were predicted within human MGC9753 mRNA, and ORF1 (nucleotide position 18-980 of NM_033419.1) was predicted as the coding region of human MGC9753 mRNA based on comparative genomics. Nucleotide sequence of mouse Mgc9753 mRNA was next determined in silico by modification of AK052486 cDNA (deleting C at the nucleotide position 37). Human MGC9753 and mouse Mgc9753 proteins were 320-amino-acid seven-transmembrane receptors with the N-terminal six-cysteine domain and an N-glycosylation site (85.0% total-amino-acid identity). Human MGC9753 protein showed 90.6% total-amino-acid identity with human CAB2 aberrant protein, which lacked the third-transmembrane domain of MGC9753 due to frame shifts within ORF. Human MGC9753 gene, consisting of eight exons, were clustered with PPP1R1B, STARD3, TCAP, PNMT, ERBB2, MGC14832 and GRB7 genes within the 120-kb region. PPP1R1B, STARD3, MGC9753, ERBB2 and GRB7 genes are co-amplified in several cases of gastric cancer. This is the first report on comprehensive characterization of the amplicon around the PPP1R1B-STARD3-TCAP-PNMT-MGC9753-ERBB2-MGC14832-GRB7 locus on human chromosome 17q12.

  6. 含F/2A序列的抗 P185erbB2人鼠嵌合抗体慢病毒表达载体的构建%Construction of the Lentiviral Expression Vector Containing F/2AFragment for Anti-P185erbB2 Mouse/Human Chimeric Antibody

    Institute of Scientific and Technical Information of China (English)

    刘芳; 李力; 张玮; 王琪

    2012-01-01

    目的 构建含 F/2A 序列的抗 P185erbB2 人鼠嵌合抗体慢病毒表达载体,观察其在 293T 细胞中的表达.方法 用具有自我剪切能力的弗林蛋白酶(Furin)/口蹄疫病毒2A多肽(F/2A)连接人鼠嵌合抗体的重链和轻链,形成一个开放阅读框 (ORF),插入慢病毒表达载体pWPI,构建重组抗P185erbB2全长人鼠嵌合抗体表达载体pWPI/H-F2A-L.以已构建的慢病毒表达载体pWPI/H-IRES-L为对照质粒.应用磷酸钙沉淀法将慢病毒载体 3 质粒系统共转染入 293T 细胞进行包装,测定病毒滴度.再感染 293T 细胞,荧光显微镜下观察 GFP 的表达和转染效率,RT-PCR、ELISA 方法分别检测嵌合抗体 mRNA和蛋白的表达.结果 经测序鉴定,pWPI/H-F2A-L与预期设计一致;pWPI/H-F2A-L组的病毒滴度为4.3×105 TU/ml,而pW-PI/H-IRES-L 组的病毒滴度为3.5×105 TU/ml;两组重组慢病毒的转染效率分别为 87.68%和 79.08%:两组重组慢病毒感染 293T 细胞后,都有嵌合重链和嵌合轻链的表达,由F/2A介导的嵌合抗体的表达水平要高于由 IRES 介导的嵌合抗体.结论 成功构建了含F/2A序列的抗P185erbB2人鼠嵌合抗体慢病毒表达载体,为今后抗P185erbB2工程抗体的研究奠定了基础.%Objective To construct the lentiviral expression vector containing F/2A fragment for anti-P185erbB2 mouse/human chimeric antibody , and detect its expression in 293T cells. Methods The heavy and light chains of chimeric antibody were joined by Furin and 2A ( F/ 2A) self-cleavage peptide and cloned into a lentiviral vector of pWPI , to generate the lentiviral ex-pression vector, pWPI/H-F2A-L Another lentiviral expression vector , pWPI/H4RES-L that had been generated already , was used as control plasmid. 293 T cells were co-transfected with the 3 helper plasmid system by using calcium phosphate precipitation , and then the virus titer was exam-ined. The 293 T cells were infected by the obtained lentiviral particles. The expression of GFP and the transfection efficiency were examined under fluorescent microscope after transfection . The expression of chimeric antibody was examined by RT -PCR and ELISA. Results Sequence analysis showed that the lentiviral expression vector pWPI/H-F2A-L was constructed correctly. The viral titer was exam-ined as 4. 3×105 TU/mL for pWPI/H2A4, group, and 3. 5×105 TU/mL for pWPI/H4RES4, group. The transfection efficiency in these two groups reached to 87. 68% and 79. 08% , respective-ly. After 293T cells were transfected with lentiviral particles , both heavy and light chains of the chi-meric antibody genes could express in the two groups. The expression level of the chimeric anti body linked by F2A was higher than that of the chimeric anti body linked by IRES . Conclusion The lentiviral expression vector containing F/2A fragment for anti-P185erbB2 mouse/human chimeric antibody was successfully constructed for further study of anti -P185erbB2 engineered antibody.

  7. Constitutively active ErbB2 regulates cisplatin-induced cell death in breast cancer cells via pro- and antiapoptotic mechanisms

    DEFF Research Database (Denmark)

    Sigurðsson, Haraldur H; Olesen, Christina Wilkens; Dybboe, Rie

    2015-01-01

    UNLABELLED: Despite the frequent expression of N-terminally truncated ErbB2 (ΔNErbB2/p95HER2) in breast cancer and its association with Herceptin resistance and poor prognosis, it remains poorly understood how ΔNErbB2 affects chemotherapy-induced cell death. Previously it was shown that ΔNErbB2...... upregulates acid extrusion from MCF-7 breast cancer cells and that inhibition of the Na(+)/H(+) exchanger (SLC9A1/NHE1) strongly sensitizes ΔNErbB2-expressing MCF-7 cells to cisplatin chemotherapy. The aim of this study was to identify the mechanism through which ΔNErbB2 regulates cisplatin-induced breast...... cancer cell death, and determine how NHE1 regulates this process. Cisplatin treatment elicited apoptosis, ATM phosphorylation, upregulation of p53, Noxa (PMAIP1), and PUMA (BBC3), and cleavage of caspase-9, -7, fodrin, and PARP-1 in MCF-7 cells. Inducible ΔNErbB2 expression strongly reduced cisplatin...

  8. Simulation of homology models for the extracellular domains (ECD) of ErbB3, ErbB4 and the ErbB2-ErbB3 complex in their active conformations.

    Science.gov (United States)

    Franco-Gonzalez, Juan Felipe; Ramos, Javier; Cruz, Victor L; Martínez-Salazar, Javier

    2013-02-01

    Epidermal growth factor receptors (EGFR) are associated with a number of biological processes and are becoming increasingly recognized as important therapeutic targets against cancer. In this work, we provide models based on homology for the extracellular domains (ECD) of ErbB3 and ErbB4 in their active conformations, including a Heregulin ligand, followed by further refinement of the models by molecular dynamics simulations at atomistic scale. We compare the results with a model built for ErbB2 based on crystallographic information and analyze the common features observed among members of the family, namely, the periscope movement of the dimerization arm and the hinge displacement of domain IV. Finally, we refine a model for the interaction of the ECDs corresponding to a ErbB2-ErbB3 heterodimer, which is widely recognized to have a high impact in cancer development.

  9. Activation of EGFR/ERBB2 via pathways involving ERK1/2, P38 MAPK, AKT and FOXO enhances recovery of diabetic hearts from ischemia-reperfusion injury.

    Science.gov (United States)

    Akhtar, Saghir; Yousif, Mariam H M; Chandrasekhar, Bindu; Benter, Ibrahim F

    2012-01-01

    This study characterized the effects of diabetes and/or ischemia on epidermal growth factor receptor, EGFR, and/or erbB2 signaling pathways on cardiac function. Isolated heart perfusion model of global ischemia was used to study the effect of chronic inhibition or acute activation of EGFR/erbB2 signaling on cardiac function in a rat model of type-1 diabetes. Induction of diabetes with streptozotocin impaired recovery of cardiac function (cardiac contractility and hemodynamics) following 40 minutes of global ischemia in isolated hearts. Chronic treatment with AG825 or AG1478, selective inhibitors of erbB2 and EGFR respectively, did not affect hyperglycemia but led to an exacerbation whereas acute administration of the EGFR ligand, epidermal growth factor (EGF), led to an improvement in cardiac recovery in diabetic hearts. Diabetes led to attenuated dimerization and phosphorylation of cardiac erbB2 and EGFR receptors that was associated with reduced signaling via extracellular-signal-regulated kinase 1/2 (ERK1/2), p38 mitogen activated protein (MAP) kinase and AKT (protein kinase B). Ischemia was also associated with reduced cardiac signaling via these molecules whereas EGF-treatment opposed diabetes and/or ischemia induced changes in ERK1/2, p38 MAP kinase, and AKT-FOXO signaling. Losartan treatment improved cardiac function in diabetes but also impaired EGFR phosphorylation in diabetic heart. Co-administration of EGF rescued Losartan-mediated reduction in EGFR phosphorylation and significantly improved cardiac recovery more than with either agent alone. EGFR/erbB2 signaling is an important cardiac survival pathway whose activation, particularly in diabetes, ischemia or following treatment with drugs that inhibit this cascade, significantly improves cardiac function. These findings may have clinical relevance particularly in the treatment of diabetes-induced cardiac dysfunction.

  10. Active G protein-coupled receptors (GPCR), matrix metalloproteinases 2/9 (MMP2/9), heparin-binding epidermal growth factor (hbEGF), epidermal growth factor receptor (EGFR), erbB2, and insulin-like growth factor 1 receptor (IGF-1R) are necessary for trenbolone acetate-induced alterations in protein turnover rate of fused bovine satellite cell cultures.

    Science.gov (United States)

    Thornton, K J; Kamanga-Sollo, E; White, M E; Dayton, W R

    2016-06-01

    Trenbolone acetate (TBA), a testosterone analog, increases protein synthesis and decreases protein degradation in fused bovine satellite cell (BSC) cultures. However, the mechanism through which TBA alters these processes remains unknown. Recent studies indicate that androgens improve rate and extent of muscle growth through a nongenomic mechanism involving G protein-coupled receptors (GPCR), matrix metalloproteinases (MMP), heparin-binding epidermal growth factor (hbEGF), the epidermal growth factor receptor (EGFR), erbB2, and the insulin-like growth factor-1 receptor (IGF-1R). We hypothesized that TBA activates GPCR, resulting in activation of MMP2/9 that releases hbEGF, which activates the EGFR and/or erbB2. To determine whether the proposed nongenomic pathway is involved in TBA-mediated alterations in protein turnover, fused BSC cultures were treated with TBA in the presence or absence of inhibitors for GPCR, MMP2/9, hbEGF, EGFR, erbB2, or IGF-1R, and resultant protein synthesis and degradation rates were analyzed. Assays were replicated at least 9 times for each inhibitor experiment utilizing BSC cultures obtained from at least 3 different steers that had no previous exposure to steroid compounds. As expected, fused BSC cultures treated with 10 n TBA exhibited increased ( BSC cultures with 10 n TBA in the presence of inhibitors for GPCR, MMP2/9, hbEGF, EGFR, erbB2, or IGF-1R suppressed ( 0.05) effect on TBA-mediated decreases in protein degradation. However, inhibition of both EGFR and erbB2 in the presence of 10 n TBA resulted in decreased ( BSC cultures treated with 10 n TBA exhibit increased ( BSC cultures.

  11. Detection of gene amplification in MYCN, C-MYC, MYCL1, ERBB2, EGFR, AKT2, and human papilloma virus in samples from cervical smear normal cytology, intraepithelial cervical neoplasia (CIN I, II, III, and cervical cancer

    Directory of Open Access Journals (Sweden)

    Dabeiba Adriana García

    2011-06-01

    Full Text Available Introducción: El cáncer cervical es el segundo cáncer más importante en mujeres a nivel mundial y es la segunda causa de muerte por cáncer en mujeres. Se ha demostrado que el proceso de carcinogénesis cervical presenta componentes tanto genéticos como epigenéticos y medio ambientales. En la actualidad, hay gran interés en la búsqueda de marcadores moleculares asociados con la progresión de esta enfermedad, uno de los posibles mecanismos y que además está poco estudiado en cáncer cervical es la amplificación génica de algunos oncogenes como la familia MYC, EGFR y AKT entre otros. Objetivos: Detectar la amplificación génica de MYCN, C-MYC, MYCL1, ERBB2, EGFR y AKT2 además de la presencia del virus de papiloma humano en cepillados cervicales en mujeres con citología normal o con neoplasia intraepitelial cervical (NIC I, II y III o con cáncer cervical. Métodos: Se genotipificó mediante reverse line blot (RLB el virus de papiloma humano (VPH y se determinó el estado de amplificación génica de los genes mencionados mediante PCR en tiempo real utilizando sondas taqman. Resultados: El VPH se encontró presente en 4% de las pacientes con citología normal, en 48% en NIC I, 63.6% en NIC II, 64% en NIC III y 70.8% en cáncer cervical. Los genes MYCN, MYCL1 y ERBB2 mostraron mayor amplificación en lesiones de alto grado y cáncer con diferencias estadísticamente significativas  a las lesiones de bajo grado y citología normal, en 39.1%, 34.7% y 30.4% respectivamente. Además, se encontraron amplificados los genes C-MYC, EGFR y AKT2, en muestras de pacientes con cáncer cervical, en 12%, 18% y 13% respectivamente. Sin embargo, no se observaron diferencias estadísticamente significativas con respecto a las lesiones de alto y bajo grado y citología normal. Conclusión: En las lesiones de alto grado como en cáncer cervical, se encuentra mayor prevalencia del virus al igual que se detectan mayor cantidad de alteraciones gen

  12. Mesenchymal stromal cells expressing ErbB-2/neu elicit protective antibreast tumor immunity in vivo, which is paradoxically suppressed by IFN-gamma and tumor necrosis factor-alpha priming.

    Science.gov (United States)

    Romieu-Mourez, Raphaëlle; François, Moïra; Abate, Amanda; Boivin, Marie-Noëlle; Birman, Elena; Bailey, Dana; Bramson, Jonathan L; Forner, Kathy; Young, Yoon-Kow; Medin, Jeffrey A; Galipeau, Jacques

    2010-10-15

    It is unknown whether mesenchymal stromal cells (MSC) can regulate immune responses targeting tumor autoantigens of low immunogenicity. We tested here whether immunization with MSC could break immune tolerance towards the ErbB-2/HER-2/neu tumor antigen and the effects of priming with IFN-γ and tumor necrosis factor-α (TNF-α) on this process. BALB/c- and C57BL/6-derived MSC were lentivirally transduced to express a kinase-inactive rat neu mutant (MSC/Neu). Immunization of BALB/c mice with nontreated or IFN-γ-primed allogeneic or syngeneic MSC/Neu induced similar levels of anti-neu antibody titers; however, only syngeneic MSC/Neu induced protective neu-specific CD8(+) T cell responses. Compared to immunization with nontreated or IFN-γ-primed syngeneic MSC/Neu, the number of circulating neu-specific CD8(+) T cells and titers of anti-neu antibodies were observed to be decreased after immunizations with IFN-γ- plus TNF-α-primed MSC/Neu. In addition, syngeneic MSC/Neu seemed more efficient than IFN-γ-primed MSC/Neu at inducing a protective therapeutic antitumor immune response resulting in the regression of transplanted neu-expressing mammary tumor cells. In vitro antigen-presenting cell assays performed with paraformaldehyde-fixed or live MSC showed that priming with IFN-γ plus TNF-α, compared to priming with IFN-γ alone, increased antigen presentation as well as the production of immunosuppressive factors. These data suggest that whereas MSC could effectively serve as antigen-presenting cells to induce immune responses aimed at tumor autoantigens, these functions are critically regulated by IFN-γ and TNF-α.

  13. PCNA、neuregulin-1、erbB-2在听神经瘤中的表达与肿瘤生物学行为相关性分析%Relevance between the expression of PCNA, neuregulin-1 and erbB-2 and biological behavior of acoustic neuroma

    Institute of Scientific and Technical Information of China (English)

    冯娟娟; 夏寅

    2011-01-01

    目的 探讨肿瘤增生细胞核抗原(proliferating cell nuclear antigen,PCNA)、神经调节因子-1(neuregulin-1)及其受体erbB-2在听神经瘤组织标本中表达的意义及其与肿瘤生长特性的相关性.方法 回顾性分析27例接受听神经瘤手术患者的临床资料,27例蜡封标本经病理证实均为听神经瘤,利用免疫组织化学方法对其病理标本石蜡切片进行PCNA、neuregulin-1、erbB-2染色.结果 在27例听神经瘤标本中,PCNA阳性率为92.6% (25/27);neuregulin-1阳性率为81.4%( 22/27),erbB-2在全部听神经瘤病理标本中均无表达.PCNA阳性表达与性别、年龄、肿瘤侧别和大小均无相关性;PCNA增生指数与病程(F=5.011,P=0.015)及肿瘤临床生长速率有关(t=-3.360,P=0.003).Neuregulin-1阳性表达强度与患者性别、年龄、肿瘤侧别和大小均无相关性,neuregulin-1表达强度在患者病程<1年组比>1年组明显增高,在肿瘤临床年生长速率<10 mm组低于肿瘤临床年生长速率≥10 mm组,但差异无统计学意义.Neuregulin-1阳性表达强度与PCNA增生指数呈正相关(r=0.425,P=0.027).结论 PCNA与肿瘤生长和细胞增生有关,神经调节因子neuregulin-1参与了听神经瘤生长的生物学行为,作为neuregulin-1功能性受体的erbB-2在听神经瘤中的表达及其所起的作用有待进一步大标本量研究论证.听神经瘤的临床行为与肿瘤增生有关,目前临床上提供的肿瘤部分临床特征可在一定程度上反映听神经瘤的增生趋势.%Objective To examin the relationship between the expression of proliferating cell nuclear antigen ( PCNA) , neuregulin-1 and its receptor erbB-2 in acoustic neuroma and the growth characteristics of the tumor. Methods The clinical information of 27 patients with acoustic neuroma were reviewed retrospectively. Paraffin embedded acoustic neuroma samples confirmed by pathology from the 27 patients were included in the study. The expression of PCNA, neuregulin-1 and erbB-2 in acoustic neuroma was determined by immunohistochemistry. Results In all the 27 cases, the positive rate of PCNA was 92.7% (25/27) and the positive rate of neuregulin-1 was 81.4% ( 22/27 ) . ErbB-2 expressed in none of the cases. There was no significant relationship between the expression of PCNA with gender, age, the side and size of the tumors, but there was significant difference between the expression of PCNA with the course(F = 5.011, P=0.015) and clinical growth rate(I= -3.360, P=0.003) of the disease. There was no significant relationship between the expression of neuregulin-1 with gender, age, the side, size and course of the tumors. Although the expression of neuregulin-1 in the tumors of course less than 1 year was higher than that of the course more than 1 year, but the difference was not statistically significant. The expression of neuregulin-1 in the tumors of clinical growth rate less than 10 mm/year was lower than that in the tumors with the clinical growth rate more than 10 mm/year, the difference was not statistically significant. The expression of neuregulin-1 and PCNA had positive correlation ( r = 0.425 , P = 0. 027 ). Conclusion PCNA is related with the growth of acoustic neuroma, and reflects proliferation activities of tumor cells in acoustic neuroma. Neuregulin-1 might participate in the biological behavior of acoustic neuroma. As the functional receptor of neuregulin-1 , the expression of erbB-2 and its role in acoustic neuroma need further study in more cases. The clinical behavior of acoustic neuroma relates to tumor growth . Some characteristics of acoustic neuroma can reflect the trend of tumorgrowth to some extent.

  14. Genetic Polymorphisms in the EGFR (R521K and Estrogen Receptor (T594T Genes, EGFR and ErbB-2 Protein Expression, and Breast Cancer Risk in Tunisia

    Directory of Open Access Journals (Sweden)

    Imen Kallel

    2009-01-01

    Full Text Available We evaluated the association of epidermal growth factor receptor (EGFR 142285G>A (R521K and estrogen receptor alpha (ESR1 2014G>A (T594T single nucleotide polymorphisms with breast cancer risk and prognosis in Tunisian patients. EGFR 142285G>A and ESR1 2014G>A were genotyped in a sample of 148 Tunisian breast cancer patients and 303 controls using PCR-RFLP method. Immunohistochemitsry was used to evaluate the expression levels of EGFR, HER2, ESR1, progesterone receptor and BCL2 in tumors. We found no evidence for an association between EGFR R521K polymorphism and breast cancer risk. However, we found that the homozygous GG (Arg genotype was more prevalent in patients with lymph node metastasis (=.03 and high grade tumors (=.011. The ESR1 2014G allele showed significant association with breast cancer risk (=.025. The GG genotype was associated with HER2 overexpression and this association withstood univariate and multivariate analyses (=.009; =.021, resp.. These data suggest that the R521K might be a prognostic factor, because it correlates with both tumor grade and nodule status. The higher expression of HER2 in ESR1 T594T GG patients suggests the possibility that ESR1 gene polymorphisms accompanied by HER2 expression might influence the pathogenesis of breast cancers.

  15. Current Status of Poly(ADP-ribose Polymerase Inhibitors as Novel Therapeutic Agents for Triple-Negative Breast Cancer

    Directory of Open Access Journals (Sweden)

    David J. Hiller

    2012-01-01

    Full Text Available Triple-negative breast cancer (TNBC is an aggressive type of breast cancer that is clinically defined as lacking estrogen and progesterone receptors, as well as being ERBB2 (HER-2 negative. Without specific therapeutic targets, TNBC carries a worse prognosis than other types of breast cancer in the absence of therapy. Research has now further differentiated breast cancer into subtypes based on genetic expression patterns. One of these subtypes, basal-like, frequently overlaps with the clinical picture of TNBC. Additionally, both TNBC and basal-like breast cancer link to BRCA mutations. Recent pharmaceutical advances have created a class of drugs, poly(ADP-ribose polymerase (PARP inhibitors, which are showing potential to effectively treat these patients. The aim of this paper is to summarize the basis behind PARP inhibitors and update the current status of their development in clinical trials for the treatment of TNBC.

  16. Novel Drugs that Target ErbB2

    Science.gov (United States)

    2012-05-01

    of pharmacological properties including antiviral, antibacterial , anti-inflammatory, antimalarial and anticancer activities (1, 2). BA also inhibits...47). Gel mobility shift assays showed that BA also decreased formation of a retarded band containing Sp proteins bound to a GC-rich...analogues exhibit a broad spectrum of pharmacologic properties including antiviral, antibacterial , anti-inflam- matory, antimalarial, and anticancer

  17. Status epilepticus

    NARCIS (Netherlands)

    Hensiek, AE; Absalom, Anthony

    2006-01-01

    Status epilepticus is defined as epileptic activity that continues for more than 30 minutes as a single seizure or as recurrent seizures without inter-ictal return of consciousness. The seizure activity is usually classified as partial or generalized. Although status epilepticus is an uncommon admis

  18. Stock Status

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — These data inform the public of the most recent stock status for all stocks (FSSI and non-FSSI) in the fishery management unit contained in a fishery managment plan....

  19. Compliance status

    Energy Technology Data Exchange (ETDEWEB)

    Black, D.G.

    1995-06-01

    This section of the 1994 Hanford Site Environmental Report summarizes the activities conducted to ensure that the Hanford Site is in compliance with federal environmental protection statutes and related Washington State and local environmental protection regulations and the status of Hanford`s compliance with these requirements. Environmental permits required under the environmental protection regulations are discussed under the applicable statute.

  20. LOXL2 induces aberrant acinar morphogenesis via ErbB2 signaling

    NARCIS (Netherlands)

    J. Chang (Jufang); M.M. Nicolau (Monica); T.R. Cox (Thomas); D. Wetterskog (Daniel); J.W.M. Martens (John); H. E Barker (Holly); J.T. Erler (Janine)

    2013-01-01

    textabstractIntroduction: Lysyl oxidase-like 2 (LOXL2) is a matrix-remodeling enzyme that has been shown to play a key role in invasion and metastasis of breast carcinoma cells. However, very little is known about its role in normal tissue homeostasis. Here, we investigated the effects of LOXL2 expr

  1. Role of Stat3 and ErbB2 in Breast Cancer

    Science.gov (United States)

    2012-10-01

    correlates with clinico -pathological characteristics. These data were recently published (Cass et al, Cancers, in press, September, 2012) and will now be...was a long term survivor [27]. Our results reveal that GJIC was low in the majority of cases , except in the QU-DB and SK-LuCi6 lines. Assuming that

  2. ErbB2 Trafficking and Signaling in Human Vestibular Schwannomas

    Science.gov (United States)

    2009-10-01

    by a kinase signaling cascade involving the MAPK kinases (MAP2K), MEK 4 and 7, and the MAPK kinase kinases (MAP3K), mixed lineage kinases ( MLK ) 1-3...phosphorylation in VS cells (Flaiz et al., 2009). Merlin also suppresses MLK -3 signaling by Thus, activation of MLK -3 in response to merlin deficiency...localization and JIPs (JNK interacting proteins) and POSH (plenty of SH3s) are scaffolding proteins that bind JNKs tethering them near MLKs , MEKs, and

  3. Role of Stat3 and ErbB2 in Breast Cancer

    Science.gov (United States)

    2013-12-01

    Ciencias de la Salud, Avda. Gomez Laguna 25, 50009, Zaragoza, Spain, and Instituto de Nanociencia de Aragón, Universidad de Zaragoza, Mariano Esquillor, s...micro- scope and the MCID-elite software (Imaging Research, St. Catharine’s Ont.). In addition, the amount of total protein extracted was also used...relative to t = 0 h was measured in two independent experiments, four wound sites per cell line, using ImageJ software . Relative cell motility was

  4. Role of Stat3 and ErbB2 in Breast Cancer

    Science.gov (United States)

    2011-10-01

    viruses , the chicken leukemia virus by Ellerman and Bang in 1908, and the Rous Sarcoma virus in 1911. Since that time, virus research and cancer...At the same time, Simian Virus 40 (SV40) gained notoriety because it was found by Eddy to be a contaminant of poliomyelitis and Adenovirus vaccines...The tumor 6    antigens are also key players in the highly efficient oncogenesis in vivo by these viruses , ie when virus is inocculated into animals

  5. The Effects of Bisphenol A (BPA) on ErbB2 Positive Breast Cancer

    Science.gov (United States)

    2010-11-01

    to the Endocrine Disruptor Bisphenol A Alters Susceptibility for Mammary Cancer (2010). (Accepted for Publication) Jenkins S, , Betancourt AM... Disruptor Bisphenol A Alters Susceptibility for Mammary Cancer (2010). (Accepted for Publication Exposure to the Endocrine Disruptor Bisphenol A... disruptors , are capable of altering endocrine signaling. Because normal endocrine signaling, especially that of the sex steroid hormones, has been shown

  6. Activation of integrin-ERBB2 signaling in undifferentiated thyroid cancer

    OpenAIRE

    2014-01-01

    Undifferentiated thyroid carcinoma is one of the most aggressive human cancers. Although genetic changes underlying this aggressive cancer remain to be elucidated, RAS mutations have been frequently identified in it. Mice harboring a mutant thyroid hormone receptor ThrbPV (ThrbPV/PV) spontaneously develop differentiated follicular thyroid carcinoma similar to human thyroid cancer. We recently demonstrated that targeting a RAS mutation (KrasG12D) to the thyroid of ThrbPV/PV mice (ThrbPV/PV ...

  7. Mechanism of erbB1 and erbB2 Hetero-Oligomerization

    Science.gov (United States)

    2004-07-01

    of this common domain in proteins with diverse functions. These data were published March of 2004 in Molecular Cell . Key research accomplishments...function in yeast which has been recently published. References none Appendices Reprint manuscript attached next page 12 Molecular Cell , Vol. 13, 677-688...mlemmon@mail.med.upenn.edu of PH domains, we could generate sufficient protein for Molecular Cell 678 Ptdlns(4,5)P2 Promiscuous Ptdlns(3)P specific

  8. ERbB2 Trafficking and Signaling in Human Vestibular Schwannomas

    Science.gov (United States)

    2011-10-01

    patients with macular degeneration and respiratory syncytial virus infections (37). A miR-21Yspecific RNA interference knockdown could be achieved...International Conference on Vestibular Schwannomas and Other CPA Lesions, Barcelona, Spain , June 2007 8 Brown, KD, Clark, J, Hansen MR. Differential...Wallerian degeneration . J Neurosci 1997;17: 1642Y59. 11. Frohnert PW, Stonecypher MS, Carroll SL. Constitutive activation of the neuregulin-1/ErbB receptor

  9. USCIS My Case Status

    Data.gov (United States)

    Department of Homeland Security — USCIS provide a way for the public who applied for U.S. citizenship to check the status of their application online. To view the status of a case, the application...

  10. CENTRAL ASSESSMENT OF COMPUTED TOMOGRAPHY BRAIN SCANS

    Directory of Open Access Journals (Sweden)

    Lesley Ann Cala

    2016-08-01

    Full Text Available Development of multislice CT (MSCT scanners since 1998 has resulted in submillimetre thick slices being able to be acquired, without increasing the radiation dose to the patient. Although the incident x-ray beam is widened in the slice thickness direction (Z-direction, the emergent x-rays fall upon multiple rows of small detectors. This means data can be collected simultaneously for more than one slice per rotation of the x-ray tube. For example, the dose received by the patient will be the same for four thin slices of 2.5 mm, as for one slice of 10 mm thickness. A 64-slice MSCT can create 0.625 mm thick slices. This leads to high diagnostic value in the detection of small abnormalities in stroke patients and in the reconstruction of data from CT angiography (CTA of the brain.

  11. Heuristic status polling

    Science.gov (United States)

    Archer, Charles J.; Blocksome, Michael A.; Heidelberger, Philip; Kumar, Sameer; Parker, Jeffrey J.; Ratterman, Joseph D.

    2011-06-07

    Methods, compute nodes, and computer program products are provided for heuristic status polling of a component in a computing system. Embodiments include receiving, by a polling module from a requesting application, a status request requesting status of a component; determining, by the polling module, whether an activity history for the component satisfies heuristic polling criteria; polling, by the polling module, the component for status if the activity history for the component satisfies the heuristic polling criteria; and not polling, by the polling module, the component for status if the activity history for the component does not satisfy the heuristic criteria.

  12. Service Level Status

    CERN Multimedia

    Lopienski, S

    2007-01-01

    Nowadays, IT departments provide, and people use, computing services of an increasingly heterogeneous nature. There is thus a growing need for a status display that groups these different services and reports status and availability in a uniform way. The Service Level Status (SLS) system addresses these needs by providing a web-based display that dynamically shows availability, basic information and statistics about various IT services, as well as the dependencies between them.

  13. SIS - Status Determination

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The Status Determination dataset within the Species Information System (SIS) contains information related to overfishing, overfished, and approaching overfished...

  14. Adolescent Weight Status

    DEFF Research Database (Denmark)

    Holstein, Bjørn Evald; Due, Pernille; Brixval, Carina Sjöberg;

    2017-01-01

    day) communication with friends through cellphones, SMS messages, or Internet (1.66, 1.03-2.67). In the full population, overweight/obese weight status was associated with not perceiving best friend as a confidant (1.59, 1.11-2.28). No associations were found between weight status and number of close...

  15. Status of APEmille

    CERN Document Server

    Bartoloni, A; Cabibbo, Nicola; Calvayrac, F; Della Morte, M; De Pietri, R; De Riso, P; Carlo, F D; Renzo, F D; Errico, W; Frezzotti, R; Giorgino, T; Heitger, J; Lonardo, A; Loukianov, M; Magazzù, G; Micheli, J; Morénas, V; Paschedag, N; Pène, O; Petronzio, Roberto; Pleiter, D; Rapuano, F; Rolf, J; Rossetti, D; Sartori, L; Simma, H; Schifano, F; Torelli, M; Tripiccione, R; Vicini, P; Wegner, P

    2002-01-01

    This paper presents the status of the APEmille project, which is essentially completed, as far as machine development and construction is concerned. Several large installations of APEmille are in use for physics production runs leading to many new results presented at this conference. This paper briefly summarizes the APEmille architecture, reviews the status of the installations and presents some performance figures for physics codes.

  16. Fighting status inequalities

    DEFF Research Database (Denmark)

    Nielsen, Morten Ebbe Juul; Landes, Xavier

    2016-01-01

    Status inequalities seem to play a fairly big role in creating inequalities in health. This article assumes that there can be good reasons to fight status inequalities in order to reduce inequalities in health. It examines whether the neorepublican ideal of non-dominance does a better job...

  17. Status epilepticus in adults.

    Science.gov (United States)

    Betjemann, John P; Lowenstein, Daniel H

    2015-06-01

    Status epilepticus is a common neurological emergency with considerable associated health-care costs, morbidity, and mortality. The definition of status epilepticus as a prolonged seizure or a series of seizures with incomplete return to baseline is under reconsideration in an effort to establish a more practical definition to guide management. Clinical research has focused on early seizure termination in the prehospital setting. The approach of early escalation to anaesthetic agents for refractory generalised convulsive status epilepticus, rather than additional trials of second-line anti-epileptic drugs, to avoid neuronal injury and pharmaco-resistance associated with prolonged seizures is gaining momentum. Status epilepticus is also increasingly identified in the inpatient setting as the use of extended electroencephalography monitoring becomes more commonplace. Substantial further research to enable early identification of status epilepticus and efficacy of anti-epileptic drugs will be important to improve outcomes.

  18. Assessment of staging, prognosis and mortality of colorectal cancer by tumor markers: receptor erbB-2 and cadherins

    Directory of Open Access Journals (Sweden)

    Jesus Eliane C.

    2005-01-01

    Full Text Available PURPOSE: To evaluate the prognostic significance and correlation with staging and degree of cell differentiation of the tumoral expression of the proteins c-erbB-2 and E-cadherin, in patients with colorectal adenocarcinoma. METHODS: The study included 117 patients with an average age of 63.1 years and an average follow-up duration of 28.1 months. The disease-free interval, survival, incidence of recurrence and specific mortality were evaluated. c-erbB-2 anti-oncoprotein antibodies (Dako were utilized via the streptavidin-biotin technique. Samples were considered to be positive for c-erbB-2 if 10% or more of the tumor cell membranes were stained.The anti-E-cadherin antibodies (Dako, evaluated this protein and is considered positive, if 50% or more of the cell membranes were stained. Statistical analysis was performed using Pearson's chi-squared test, Fisher's exact test, Kaplan-Meier's estimator, the log-rank test and Wilcoxon's test (Breslow version, setting the level of statistical significance at 5% (p<0.05. RESULTS: 52 of 108 patients studied for c-erbB-2 were positive (48,1%, 47 of 93 patients studied for E-cadherin were negative (50,5%. These data do not express any correlation with TNM (tumor, node and metastasis staging and the degree of cell differentiation or with the tumor recurrence rate. The disease-free interval among patients who were positive for c-erbB-2 and negative for E-cadherin was 68.0 months and did not differ from those with c-erbB-2 negative and E-cadherin positive ( 55.0 months - p = 0.5510. The average survival among patients positive for c-erbB-2 and negative for E-cadherin was 75 months without statistical significance difference with the other group ( 61 months - p = 0.5256. Specific mortality occurred in 20.0% of the cases and did not correlate with the expression of c-erbB-2 (p=0,446, E-cadherin (p=0,883. CONCLUSION: The tumoral expression of c-erbB-2 and E-cadherin did not demonstrate a correlation with the staging and degree of cell differentiation, and it did not present prognostic value regarding disease recurrence, disease-free interval, survival and specific mortality among patients with colorectal adenocarcinoma.

  19. Small Molecule Tyrosine Kinase Inhibitors of ErbB2/HER2/Neu in the Treatment of Aggressive Breast Cancer

    Directory of Open Access Journals (Sweden)

    Richard L. Schroeder

    2014-09-01

    Full Text Available The human epidermal growth factor receptor 2 (HER2 is a member of the erbB class of tyrosine kinase receptors. These proteins are normally expressed at the surface of healthy cells and play critical roles in the signal transduction cascade in a myriad of biochemical pathways responsible for cell growth and differentiation. However, it is widely known that amplification and subsequent overexpression of the HER2 encoding oncogene results in unregulated cell proliferation in an aggressive form of breast cancer known as HER2-positive breast cancer. Existing therapies such as trastuzumab (Herceptin® and lapatinib (Tyverb/Tykerb®, a monoclonal antibody inhibitor and a dual EGFR/HER2 kinase inhibitor, respectively, are currently used in the treatment of HER2-positive cancers, although issues with high recurrence and acquired resistance still remain. Small molecule tyrosine kinase inhibitors provide attractive therapeutic targets, as they are able to block cell signaling associated with many of the proposed mechanisms for HER2 resistance. In this regard we aim to present a review on the available HER2 tyrosine kinase inhibitors, as well as those currently in development. The use of tyrosine kinase inhibitors as sequential or combinatorial therapeutic strategies with other HER family inhibitors is also discussed.

  20. The Role of the Rab Coupling Protein in ErbB2-Driven Mammary Tumorigenesis and Metastasis

    Science.gov (United States)

    2014-10-01

    5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Pierre-Luc Boulay Julie-Émilie Huot-Marchand, Cynthia Lavoie, Dongmei Zuo Laura Jones...Cynthia Lavoie, Julie M. Livingstone, Laura Jones, Shirley Campbell, Dongmei Zuo, Jim C. Norman, Gordon Mills, Eric Bonneil, Mike Hallet, Morag Park and...acetonitrile (0.2% FA) and a 600 nl/min flow rate on a NanoLC-2D system (Eksigent) connected to an LTQ- Orbitrap Elite (Thermo Fisher Scientific). Each full

  1. Differential Control of ErBB2 Surface Expression in Breast Cancer Cells by an Alternatively Spliced Form of ERBIN

    Science.gov (United States)

    2005-05-01

    interacting proteins , we found that all three hSnf7s interacted with AIP1, a mammalian Brolp-containing protein involved in cellular vacuolization and apoptosis. Mapping experiments showed that the N-terminus of Alp1 containing both a Brol and an alpha-helical domain were required for interaction with hSnf7-1, Snf7-1 did not interact with another human Brol-containing molecule, rhophilin-2. Co-immunoprecipitation experiments confirmed the in vivo interaction of hSnf7-1 and AlP1. Immunofluorescence experiments showed that hSnf7-1 recruited cytosolic AIP1 to the Snf7-induced

  2. NAIP Status Maps Gallery

    Data.gov (United States)

    Farm Service Agency, Department of Agriculture — NAIP Status Maps Gallery. These maps illustrate what aerial imagery collection is planned, whats been collected, when it is available and how it is available. These...

  3. Deadline Compliance Status Reports

    Data.gov (United States)

    Department of Housing and Urban Development — These monthly Deadline Compliance Status Reports assist Participating Jurisdictions and HUD Field Offices in monitoring compliance with the 2-year commitment and...

  4. Aleutian Goose Status Report

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — This 1995-96 status report includes the most recent observations of Aleutian Canada geese populations wintering in the El Sobrante and East San Francisco Bay areas...

  5. STATUS GIZI DAN STATUS KESEHATAN SUKU BADUY

    Directory of Open Access Journals (Sweden)

    Faisal Anwar

    2012-03-01

    Full Text Available 800x600 Normal 0 false false false IN X-NONE X-NONE /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-parent:""; mso-padding-alt:0cm 5.4pt 0cm 5.4pt; mso-para-margin:0cm; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:10.0pt; font-family:"Calibri","sans-serif"; mso-bidi-font-family:"Times New Roman";} The objectives of the study were: (1 To analyze the socio-economic and demographic characteristics of Baduy people; (2 To analyze the health status and nutritional status of Baduy people and its influential factors. This research is an explorative and descriptive study on the socio-cultural aspects of food system. The data were collected through a direct interview and discussion with respondents as well as a direct observation at the location of respondents. A sample size of 338 households was drawn from the population. To obtain the data on the cultural aspects, history and  socio aspect of food, in-depth interviews was conducted with 19 key persons. The study was last for 12 months. In Outer Baduy, the factors significantly related to nutritional status are age, number of household size, income, nutritional knowledge, and wife’s ability to read. In Moslem Baduy, only age and income are related to the nutritional status of children. In Moslem Baduy and the Outer Baduy, the correlation between age and W/A or W/H is similar: namely, the higher the age, the lower would the Z-score for the W/A or W/H. The income is significantly correlated to the child nutritional status according to Z-score for W/A with a high correlation coefficient, that is, 0.61. This means that the higher the income, the higher would be the Z-score value for the W/A.  The distribution of adults according to BMI classification in Outer Baduy it shows that 12.7% husbands and 17.6% wives are thin (wasted, while the

  6. STATUS EPILEPTICUS: A REVIEW

    Directory of Open Access Journals (Sweden)

    B. Adibeik

    2009-01-01

    Full Text Available ObjectiveStatus Epilepticus (SE has been described as a series of major motor seizure without recovery of consciousness between seizures.SE is a medical emergency that requires prompt diagnosis and appropriate treatment.In this article we shall conclude history, epidemiology, etiology, risk factors, thebest management as well as the prognosis of the condition.Keywords:Status Epilepticus (SE, adults, children, neonates.

  7. Status of ADSW 2005

    DEFF Research Database (Denmark)

    Hartmann, H.; Ahring, Birgitte Kiær

    2006-01-01

    The status of the recent developments in anaerobic digestion of solid waste (ADSW) is outlined on the basis of a selection of papers presented at the 4(th) International Symposium on ADSW 2005.......The status of the recent developments in anaerobic digestion of solid waste (ADSW) is outlined on the basis of a selection of papers presented at the 4(th) International Symposium on ADSW 2005....

  8. Status of numerical relativity

    Indian Academy of Sciences (India)

    Masaru Shibata

    2004-10-01

    I describe the current status of numerical relativity from my personal point of view. Here, I focus mainly on explaining the numerical implementations necessary for simulating general relativistic phenomena such as the merger of compact binaries and stellar collapse, emphasizing the well-developed current status of such implementations that enable simulations for several astrophysical phenomena. Some of our latest results for simulation of binary neutron star mergers are briefly presented.

  9. Refractory status epilepticus

    Directory of Open Access Journals (Sweden)

    Sanjay P Singh

    2014-01-01

    Full Text Available Refractory status epilepticus is a potentially life-threatening medical emergency. It requires early diagnosis and treatment. There is a lack of consensus upon its semantic definition of whether it is status epilepticus that continues despite treatment with benzodiazepine and one antiepileptic medication (AED, i.e., Lorazepam + phenytoin. Others regard refractory status epilepticus as failure of benzodiazepine and 2 antiepileptic medications, i.e., Lorazepam + phenytoin + phenobarb. Up to 30% patients in SE fail to respond to two antiepileptic drugs (AEDs and 15% continue to have seizure activity despite use of three drugs. Mechanisms that have made the treatment even more challenging are GABA-R that is internalized during status epilepticus and upregulation of multidrug transporter proteins. All patients of refractory status epilepticus require continuous EEG monitoring. There are three main agents used in the treatment of RSE. These include pentobarbital or thiopental, midazolam and propofol. RSE was shown to result in mortality in 35% cases, 39.13% of patients were left with severe neurological deficits, while another 13% had mild neurological deficits.

  10. STATUS GIZI BATITA

    Directory of Open Access Journals (Sweden)

    Agustina Lubis

    2012-10-01

    Full Text Available Keadaan gizi golongan rawan khususnya anak batita (bawah tiga tahun dapat dipakai sebagai petunjuk keadaan gizi masyarakat. Penentuan status gizi biasanya dilakukan atas dasar pengukuran berat dan tinggi badan dengan menggunakan indeks berat menurut umur, berat menurut tinggi badan atau tinggi menurut umur. Prevalensi kurang gizi yang tinggi pada anak Batita menjadi petunjuk bahwa status gizi masyarakat tersebut masih rendah. Banyak faktor yang diduga mempengaruhi status gizi pada Batita, seperti faktor sosial, lingkungan dan penyakit infeksi. Untuk mengetahui seberapa jauh peran dari faktor-faktor tersebut di atas, dilakukan analisis data ini dengan menggunakan indeks anthropometri berat badan menurut umur.Sumber data yang digunakan adalah hasil Survei Kesejahteraan Keluarga Indonesia 1992 (IFLS. Penelitian ini bersifat cros sectional dan dilakukan di tujuh propinsi di Indonesia. Sebagai unit analisis adalah anak Batita (umur 1-3 tahun, dengan jumlah 1540 populasi.Hasil penelitian menunjukkan ada beberapa faktor yang berperan dalam status gizi anak antara lain adalah urutan kelahiran, pendidikan ibu, diare, panas dan jumlah anggota rumah tangga. Pola makan tidak mempengaruhi status gizi anak laki-laki ataupun anak perempuan. Besarnya anggota rumah tangga walaupun pada analisis bivariat memberikan pengaruh yang bermakna namun pada analisis multivariat tidak memberikan pengaruh yang bermakna, baik pada anak laki-laki ataupun perempuan. pada analisis multivariat untuk anak laki-laki hanya variabel unrutan kelahiran dan pendidikan ibu yang menunjukkan risiko yang bermakna. Sedangkan pada anak perempuan terdapat tiga variabel yang memberikan risiko yang bermakna yaitu urutan keluarga, diare dan panas.

  11. FRIB Cryogenic Plant Status

    Energy Technology Data Exchange (ETDEWEB)

    Dixon, Kelly D. [Thomas Jefferson National Accelerator Facility (TJNAF), Newport News, VA (United States); Ganni, Venkatarao [Thomas Jefferson National Accelerator Facility (TJNAF), Newport News, VA (United States); Knudsen, Peter N. [Thomas Jefferson National Accelerator Facility (TJNAF), Newport News, VA (United States); Casagranda, Fabio [Michigan State Univ., East Lansing, MI (United States)

    2015-12-01

    After practical changes were approved to the initial conceptual design of the cryogenic system for MSU FRIB and an agreement was made with JLab in 2012 to lead the design effort of the cryogenic plant, many activities are in place leading toward a cool-down of the linacs prior to 2018. This is mostly due to using similar equipment used at CHLII for the 12 GeV upgrade at JLab and an aggressive schedule maintained by the MSU Conventional Facilities department. Reported here is an updated status of the cryogenic plant, including the equipment procurement status, plant layout, facility equipment and project schedule.

  12. New Service Status Board

    CERN Multimedia

    2013-01-01

    On Monday 14 October, the Service Status Board for GS and IT will change. The new Status Board will be integrated with the CERN Service Portal and with the CERN Service Catalogue.   As of today, the SSB will display “Service Incidents”, “Planned Interventions” and “Service Changes”. References valid from 14 October: CERN SSB at https://cern.ch/ssb Computing SSB (previously IT SSB) at https://cern.ch/itssb   Nicole Cremel, IT and GS Service Management Support

  13. Nutritional Status Assessment

    Science.gov (United States)

    Smith, Scott M.

    2008-01-01

    Nutritional Status Assessment (Nutrition) is the most comprehensive inflight study done by NASA to date of human physiologic changes during long-duration space flight; this includes measures of bone metabolism, oxidative damage, nutritional assessments, and hormonal changes. This study will impact both the definition of nutritional requirements and development of food systems for future space exploration missions to the Moon and Mars. This experiment will also help to understand the impact of countermeasures (exercise and pharmaceuticals) on nutritional status and nutrient requirements for astronauts.

  14. Stellarator status, 1989

    Energy Technology Data Exchange (ETDEWEB)

    Lyon, J.F. (Oak Ridge National Lab., TN (USA)); Grieger, G.; Rau, F. (Max-Planck-Institut fuer Plasmaphysik, Garching (Germany, F.R.)); Iiyoshi, A. (National Inst. for Fusion Science, Nagoya (Japan)); Navarro, A.P. (Centro de Investigaciones Energeticas, Medioambientales y Tecnologicas, Madrid (Spain)); Kovrizhnykh, L.M. (AN SSSR, Moscow (USSR). Inst. Obshchey Fiziki); Pavlichenko, O.S. (AN Ukrain

    1990-07-01

    The present status of stellarator experiments and recent progress in stellarator research (both experimental and theoretical) are reported by groups in the United States, the USSR, Japan, Australia, and the European Community (the Federal Republic of Germany and Spain). Experiments under construction and studies of large, next-generation stellarators are also described. 73 refs., 11 figs., 4 tabs.

  15. Angola: Country Status Report.

    Science.gov (United States)

    Bruhn, Thea C.

    A survey of the status of language usage in Angola begins with an overview of the usage and distribution of Portuguese as the official language, and the four most significant native languages and dialects spoken there: Umbundu, Kimbundu, Kikongo, and Lunda-Chokwe. The introduction of Spanish through Cuban trainers, teachers, and military advisors…

  16. Uigur. Materials Status Report.

    Science.gov (United States)

    Center for Applied Linguistics, Washington, DC. Language/Area Reference Center.

    The materials status report for Uigur, a Turkic language spoken in the Sinkiang-Uigur Autonomous Region in northwest China and in the Soviet Socialist Republics of Kazakh and Uzbek, is one of a series intended to provide the nonspecialist with a picture of the availability and quality of texts for teaching various languages to English speakers.…

  17. Current status of DUMAND

    Energy Technology Data Exchange (ETDEWEB)

    Grieder, P.K.F.

    We give a brief description of the scientific aims of the DUMAND project, of the system lay-out and its capabilities, together with some technical details of the detector modules. Subsequently we present the anticipated project schedule and construction strategy, followed by an account of the present project status.

  18. Somalia: Country Status Report.

    Science.gov (United States)

    McFerren, Margaret

    A survey of the status of language usage in Somalia begins with an overview of the usage patterns of Somali, the official language, and three languages previously used officially: English, Italian, and Arabic. The cultural context that for many years has supported the usage of a single native language for communication and administration is also…

  19. STATUS EPILEPTICUS: A REVIEW

    Directory of Open Access Journals (Sweden)

    B. Adibeik

    2008-10-01

    Full Text Available ObjectiveStatus Epilepticus (SE has been described as a series of major motor seizure without recovery of consciousness between seizures.SE is a medical emergency that requires prompt diagnosis and appropriate treatment.In this article we shall conclude history, epidemiology, etiology, risk factors, thebest management as well as the prognosis of the condition.

  20. Algeria: Country Status Report.

    Science.gov (United States)

    McFerren, Margaret

    A survey of the status of language usage in Algeria begins with an overview of the usage patterns of Arabic, the Berber languages, and French. The country's return to Arabic as its official language after independence from France in 1962 is discussed along with the resultant language planning, issues of language of instruction at the elementary,…

  1. NASA Armstrong Status

    Science.gov (United States)

    Jacobson, Steven R.

    2014-01-01

    Armstrong (formerly Dryden) Flight Research Center continues it's legacy of exciting work in the area of dynamics and control of advanced vehicle concepts. This status presentation highlights the research and technology development that Armstrong's Control and Dynamics branch is performing in the areas of Control of Flexible Structures and Automated Cooperative Trajectories.

  2. Amharic. Materials Status Report.

    Science.gov (United States)

    Center for Applied Linguistics, Washington, DC. Language/Area Reference Center.

    The materials status report for Amharic, the dominant language of Ethiopia, is one of a series intended to provide the nonspecialist with a picture of the availability and quality of texts for teaching various languages to English speakers. The report consists of: (1) a brief narrative description of Amharic, the areas where it is spoken, its…

  3. Women Status and their Discrimination

    OpenAIRE

    PEŠKOVÁ, Pavlína

    2008-01-01

    My work deal with women status and their discrimination. Chapter one contains women status in different historical periods and development of their status to bigger equal with men. There is also written about present feminist trends. Chapter two is about women discrimination. There is about women´ job discrimination, job segregation according to gender and inequality in payment. There is also written about women status at home and unequal duties at home among family mates. Chapter three is ab...

  4. Health status of newcomers.

    Science.gov (United States)

    Matuk, L C

    1996-01-01

    This article presents and discusses findings on the health status of newcomers residing in Windsor, Ontario. The data are part of a larger study, which was based on the Ontario Health Survey's questionnaire. Data were collected from 548 newcomers through home visits, focus groups, mail surveys, and telephone interviews. Descriptive multivariate analyses focused on main areas in newcomers' physical and mental health status and their access to health services. The findings identified that most newcomers do not have acute, life-threatening physical problems or chronic illness. They do not experience major problems with access to health care or activity limitations. Men are happier, more satisfied with their health, and less stressed than women. This study has implications for adoption of sensitive transcultural approaches to promote newcomers' health. Special challenges lie in women's health and mental health.

  5. Status of memory loss.

    LENUS (Irish Health Repository)

    Iyer, Parameswaran Mahadeva

    2012-01-01

    A 72-year-old woman presented with first onset of seizure with no prior history of cognitive dysfunction. EEG revealed focal non-convulsive status epilepticus. MRI brain showed a left temporal non-enhancing lesion. Temporal pole biopsy showed acute neuronal necrosis and astrocyte hyperplasia together with extensive amyloid plaques and neurofibrillary tangles. Perivascular oligodendroglial hyperplasia was present. Postmortem examination revealed extensive plaque and tangle disease. Perivascular oligodendroglial hyperplasia was limited to the left temporal area. The presence of focal perivascular oligodendroglial hyperplasia in the left temporal cortex, combined with extensive plaque and tangle disease may have contributed to the focal status epilepticus in this patient. Although the presence of focal perivascular oligodendroglial hyperplasia has been reported in cases of temporal lobe epilepsy, it has not been reported as a cause of seizure in patients with Alzheimer\\'s disease previously. Further studies for clinical-pathologic correlation would be required to confirm this hypothesis.

  6. Evolutionary status of Entamoeba

    Institute of Scientific and Technical Information of China (English)

    DONG Jiuhong; WEN Jianfan; XIN Dedong; LU Siqi

    2004-01-01

    In addition to its medical importance as parasitic pathogen, Entamoeba has aroused people's interest in its evolutionary status for a long time. Lacking mitochondrion and other intracellular organelles common to typical eukaryotes, Entamoeba and several other amitochondrial protozoans have been recognized as ancient pre-mitochondriate eukaryotes and named "archezoa", the most primitive extant eukaryotes. It was suggested that they might be living fossils that remained in a primitive stage of evolution before acquisition of organelles, lying close to the transition between prokaryotes and eukaryotes. However, recent studies revealed that Entamoeba contained an organelle, "crypton" or "mitosome", which was regarded as specialized or reductive mitochondrion. Relative molecular phylogenetic analyses also indicated the existence or the probable existence of mitochondrion in Entamoeba. Our phylogenetic analysis based on DNA topoisomerase II strongly suggested its divergence after some mitchondriate eukaryotes. Here, all these recent researches are reviewed and the evolutionary status of Entamoeba is discussed.

  7. Experimental status of physics

    Indian Academy of Sciences (India)

    H Yamamoto

    2000-07-01

    In a short period of time, we will have a large amount of results from -factories including ones on CP violation. In this talk, we briefly review the current experimental status of -physics. After a quick description of -facilities, we divide this vast field into two categories: (1) weak interaction and QCD, (2) unitarity triangle and CP violation. Only a few critical items are selected in each category for the sake of time and space.

  8. Supersymmetry: Experimental Status

    CERN Document Server

    Ulmer, Keith A

    2016-01-01

    This talk presents results from the CMS and ATLAS Collaborations from searches for physics beyond the Standard Model motivated by supersymmetry from Run 1 of the LHC. Representative searches are described to illustrate the diverse nature of the search program in both background estimation techniques and final state topologies. The status of preparation for Run 2 searches at 13 TeV is also presented.

  9. DUMAND II status report

    Energy Technology Data Exchange (ETDEWEB)

    Aoki, T. (ICRR, University of Tokyo, Japan (JP)); Becker-Szendy, R.; Bosetti, P.; Boynton, P.E.; Bradner, H.; Camerini, U.; Clem, J.; Commichau, V.; Dau, D.; Dye, S.; Grieder, P.K.F.; Hayashino, T.; Hazen, E.; Jaworski, M.; Kitamura, T.; Kobayakawa, K.; Koske, P.; Learned, J.G.; Ley, C.; Lord, J.J.; March, R.; Matsuno, S.; Minkowski, P.; Mitsui, K.; O' Connor, D.; Ohashi, Y.; Okada, A.; Peterson, V.Z.; Rathlev, J.; Roberts, A.; Roos, C.E.; Sakuda, M.; Samm, D.; Stenger, V.J.; Tanaka, S.; Uehara, S.; Webster, M.; Wilkins, G.; Wilkes, R.J.; Yamaguchi, A.; Yamamoto, I.; Young, K.K. (University of Bern, Switzerland (CH) Boston University, (USA) University of Hawaii, (USA) University of Kiel, Germany (DE) Kobe University, Japan (JP) Kinki University, Japan (JP) Okayama Science University, Japan (JP) Scripps Institute of Oceanography, (USA) Tohoku University, Japan (JP) ICRR, University of tokyo, Japan (JP) NLHEP Tsukuba, Japan (JP) Vanderbilt University, (USA) University of Washington, (US

    1991-04-05

    The scientific goals, design, capabilities, and status of the DUMAND II detector system are described. In June, 1989, the High Energy Physics Advisory Panel recommended support for construction of DUMAND II to the U.S. Department of Energy. Funding began in 1990, and prototype development for various detector subsystems is under way. Current plans include deployment of the shore cable, junction box and three strings of optical detector modules in 1992, and expansion to the full 9-string configuration in 1993.

  10. DUMAND II status report

    Science.gov (United States)

    Aoki, T.; Becker-Szendy, R.; Bosetti, P.; Boynton, P. E.; Bradner, H.; Camerini, U.; Clem, J.; Commichau, V.; Dau, D.; Dye, S.; Grieder, P. K. F.; Hayashino, T.; Hazen, E.; Jaworski, M.; Kitamura, T.; Kobayakawa, K.; Koske, P.; Learned, J. G.; Ley, C.; Lord, J. J.; March, R.; Matsuno, S.; Minkowski, P.; Mitsui, K.; O'Connor, D.; Ohashi, Y.; Okada, A.; Peterson, V. Z.; Rathlev, J.; Roberts, A.; Roos, C. E.; Sakuda, M.; Samm, D.; Stenger, V. J.; Tanaka, S.; Uehara, S.; Webster, M.; Wilkins, G.; Wilkes, R. J.; Yamaguchi, A.; Yamamoto, I.; Young, K. K.

    1991-04-01

    The scientific goals, design, capabilities, and status of the DUMAND II detector system are described. In June, 1989, the High Energy Physics Advisory Panel recommended support for construction of DUMAND II to the U.S. Department of Energy. Funding began in 1990, and prototype development for various detector subsystems is under way. Current plans include deployment of the shore cable, junction box and three strings of optical detector modules in 1992, and expansion to the full 9-string configuration in 1993.

  11. The status of GALLEX

    Energy Technology Data Exchange (ETDEWEB)

    Cribier, M. (CEA Centre d' Etudes Nucleaires de Saclay, 91 - Gif-sur-Yvette (France). Dept. de Physique des Particules Elementaires)

    1990-01-01

    The present status of the Gallium Solar Neutrino Experiment performed by the GALLEX Collaboration in the Gran Sasso Underground Laboratory is described. The implementation phase of this experiment is now completed, the whole gallium is at hand and data taking starts now. After a short introduction and an outline of the basic experimental procedure, details will be given on different parts of the experiment and on some background. 14 refs., 2 figs.

  12. SalSA status

    Energy Technology Data Exchange (ETDEWEB)

    Connolly, Amy [Department of Physics and Astronomy, University College London, Gower Street, London WC1E 6BT (United Kingdom)], E-mail: amyc@hep.ucl.ac.uk

    2009-06-01

    I review the status of SalSA, a proposed antenna array in a large volume salt formation for detecting ultra-high energy neutrinos. We report on measurements taken in 2007 of attenuation lengths in the 125-900 MHz frequency range at the Cote Blanche salt mine near New Iberia, Louisiana, which is the most precise in situ measurement of attenuation lengths in salt to date. We comment on the impact of these measurements on the feasibility of SalSA.

  13. ATLAS construction status

    CERN Document Server

    Jenni, P

    2006-01-01

    The ATLAS detector is being constructed at the LHC, in view of a data-taking start-up in 2007. This report concentrates on the progress and the technical challenges of the detector construction, and summarizes the status of the work as of August 2004. The project is on track to allow the highly motivated ATLAS collaboration to enter into a new exploratory domain of high-energy physics in 2007.

  14. QCDSP A status report

    CERN Document Server

    Chen, D; Christ, N H; Edwards, R G; Fleming, G R; Gara, A; Hansen, S; Jung, C; Kähler, A L; Kennedy, A D; Kilcup, G W; Luo, Y; Malureanu, C I; Mawhinney, Robert D; Parsons, H; Sexton, J C; Sui, C Z; Vranas, P M; Chen, Dong; Chen, Ping; Christ, Norman H.; Edwards, Robert G.; Fleming, George R.; Gara, Alan; Hansen, Sten; Jung, Chulwoo; Kaehler, Adrian L.; Kennedy, Anthony D.; Kilcup, Gregory W.; Luo, Yubing; Malureanu, Catalin I.; Mawhinney, Robert D.; Parsons, John; Sexton, James C.; Sui, ChengZhong; Vranas, Pavlos M.

    1997-01-01

    The QCDSP machine at Columbia University has grown to 2,048 nodes achieving a peak speed of 100 Gigaflops. Software for quenched and Hybrid Monte Carlo (HMC) evolution schemes has been developed for staggered fermions, with support for Wilson and clover fermions under development. We provide an overview of the runtime environment, the current status of the QCDSP construction program and preliminary results not presented elsewhere in these proceedings.

  15. Sibling Status Effects: Adult Expectations.

    Science.gov (United States)

    Baskett, Linda Musun

    1985-01-01

    This study attempted to determine what expectations or beliefs adults might hold about a child based on his or her sibling status alone. Ratings on 50 adjective pairs for each of three sibling status types, only, oldest, and youngest child, were assessed in relation to adult expectations, birth order, and parental status of rater. (Author/DST)

  16. Mental Representations of Social Status

    Science.gov (United States)

    Chiao, Joan Y.; Bordeaux, Andrew R.; Ambady, Nalni

    2004-01-01

    How do people think about social status? We investigated the nature of social status and number representations using a semantic distance latency test. In Study 1, 21 college students compared words connoting different social status as well as numbers, which served as a control task. Participants were faster at comparing occupations and numbers…

  17. Convulsive status epilepticus in children

    Directory of Open Access Journals (Sweden)

    Redžek-Mudrinić Tatjana

    2010-01-01

    Full Text Available Introduction. Convulsive status epilepticus is the most urgent neurological medical emergency in children. Generalized convulsive status epilepticus is the most common and life-threatening type of status epilepticus. It is not a syndrome in the same sense as febrile convulsions, benign rolandic epilepsy, and infantile polymorphic epilepsy. These latter disorders have a tight age frame, seizure semiology, and a reasonably predictable outcome. Episodes of convulsive status epilepticus can occur in each: occasionally in symptomatic and febrile convulsions, and Lennox Gastaut syndrome, rarely in benign rolandic epilepsy, and West syndrome. Etiology of convulsive status epilepticus. Status epilepticus has many causes, which vary depending on the age and patient population. Convulsive status epileptucus continues to be associated with significant neurological morbidity and mortality, with different hazards and outcome. Although the outcome is dependent on etiology, it is known that appropriate early management may reduce mortality and some of the morbidity associated with convulsive status epilepticus. Discussion. Status epilepticus is a disorder in which the mechanisms attempting at terminating the seizure fail. Continued convulsive activity in convulsive status epilepticus results in decompensation of all organs and systems, thus being life threatening. Seizure activity in convulsive status epilepticus is associated with neuronal damage. The aim should be to halt this activity urgently, using, ideally, a 100% effective drug, administered quickly, without compromising the consciousness level or producing other negative effects on cardiovascular, respiratory function or other unexpected effects.

  18. Status epilepticus in scleromyxedema

    Institute of Scientific and Technical Information of China (English)

    Soifa Markoula; Soifa Zouroudi; Soitrios Giannopoulos; Kimon Tsoukanelis; Ananstasia Zikou; Athanassios P Kyritsis

    2016-01-01

    Scleromyxedema is a rare dermatologic disorder, characterized by erythematous or yelowish lichenoid waxy papules. Neurological manifestations are rare but wel-recognized. A 51-year-old woman, diagnosed with scleromyxedema, was admitted to the hospital with status epilepticus, caused by brain lesions, as disclosed in a brain magnetic resonance imaging (MRI). The patient was treated with anticonvulsants and corticosteroids and gradualy recovered fuly. A complete remission of the lesions was shown in a folow-up brain MRI. In cases with scleromyxedema and the presence of neurological manifestations, we need to pay attention to central nervous system involvement, especialy when combined with brain MRI lesions, and treat the patient appropriately.

  19. NESTOR: a status report

    Science.gov (United States)

    Bottai, S.; Anassontzis, E. G.; Athanasopoulos, C.; Barone, M.; Grammatikakis, G.; Katsanevas, S.; Kourkoumelis, C.; Manousakis-Katsikakis, A.; Resvanis, L. K.; Siotis, I.; Sotiriou, S. A.; Voulgaris, C. G.; Minkowski, P.; Grieder, P. K. F.; Ball, A. E.; Cartacci, A. M.; Monteleoni, B.; Naumov, V. A.; Trasatti, L.; Fahrun, E.; Keusen, U.; Koske, P.; Rathlev, J.; Schmidt, N. P.; Voigt, G.; Bezrukov, L. B.; Butkevich, A. V.; Dedenko, L. G.; Karaevsky, S. K.; Mironovich, A. A.; Zakharov, L. M.; Zheleznykh, I. M.; Zhukov, V. A.; Demidova, T. A.; Deineko, A. O.; Eremeev, A. P.; Paka, V. T.; Permyakov, A. A.; Platonov, M. N.; Rukol, V. Kh.; Sheremet, N. A.; Surin, N. M.; Albul, V. I.; Ledenev, V. V.

    2000-05-01

    NESTOR is an underwater neutrino astrophysics laboratory to be located in the international waters of the southwest of Greece. The first phase of this experiment is the construction and deployment of one hexagonal tower consisting of 168 optical modules, with effective area of 20000m2 for E >= TeV neutrinos. Over the past few years detailed studies of the site have been carried out while many tests have been performed. The current status of the preparation of the experiment and the future plans will be presented

  20. NESTOR: a status report

    Energy Technology Data Exchange (ETDEWEB)

    Bottai, S.; Anassontzis, E.G; Athanasopoulos, C.; Barone, M.; Grammatikakis, G.; Katsanevas, S.; Kourkoumelis, C.; Manousakis-Katsikakis, A.; Resvanis, L.K.; Siotis, I.; Sotiriou, S. A.; Voulgaris, C G.; Minkowski, P.; Grieder, P.K.F.; Ball, A.E.; Cartacci, A.M.; Monteleoni, B.; Naumov, V.A.; Trasatti, L.; Fahrun, E.; Keusen, U.; Koske, P.; Rathlev, J.; Schmidt, N.P.; Voigt, G.; Bezrukov, L.B.; Butkevich, A. V.; Dedenko, L.G.; Karaevsky, S.K.; Mironovich, A.A.; Zakharov, L.M.; Zheleznykh, I.M.; Zhukov, V.A.; Demidova, T.A.; Deineko, A.O.; Eremeev, A.P.; Paka, V.T.; Permyakov, A.A.; Platonov, M.N.; Rukol, V.Kh.; Sheremet, N.A.; Surin, N.M.; Albul, V.I.; Ledenev, V.V

    2000-05-01

    NESTOR is an underwater neutrino astrophysics laboratory to be located in the international waters of the southwest of Greece. The first phase of this experiment is the construction and deployment of one hexagonal tower consisting of 168 optical modules, with effective area of 20000m{sup 2} for E {>=} TeV neutrinos. Over the past few years detailed studies of the site have been carried out while many tests have been performed. The current status of the preparation of the experiment and the future plans will be presented.

  1. Model Validation Status Review

    Energy Technology Data Exchange (ETDEWEB)

    E.L. Hardin

    2001-11-28

    The primary objective for the Model Validation Status Review was to perform a one-time evaluation of model validation associated with the analysis/model reports (AMRs) containing model input to total-system performance assessment (TSPA) for the Yucca Mountain site recommendation (SR). This review was performed in response to Corrective Action Request BSC-01-C-01 (Clark 2001, Krisha 2001) pursuant to Quality Assurance review findings of an adverse trend in model validation deficiency. The review findings in this report provide the following information which defines the extent of model validation deficiency and the corrective action needed: (1) AMRs that contain or support models are identified, and conversely, for each model the supporting documentation is identified. (2) The use for each model is determined based on whether the output is used directly for TSPA-SR, or for screening (exclusion) of features, events, and processes (FEPs), and the nature of the model output. (3) Two approaches are used to evaluate the extent to which the validation for each model is compliant with AP-3.10Q (Analyses and Models). The approaches differ in regard to whether model validation is achieved within individual AMRs as originally intended, or whether model validation could be readily achieved by incorporating information from other sources. (4) Recommendations are presented for changes to the AMRs, and additional model development activities or data collection, that will remedy model validation review findings, in support of licensing activities. The Model Validation Status Review emphasized those AMRs that support TSPA-SR (CRWMS M&O 2000bl and 2000bm). A series of workshops and teleconferences was held to discuss and integrate the review findings. The review encompassed 125 AMRs (Table 1) plus certain other supporting documents and data needed to assess model validity. The AMRs were grouped in 21 model areas representing the modeling of processes affecting the natural and

  2. Status of GENEUS

    Directory of Open Access Journals (Sweden)

    Srdinko Th.

    2012-05-01

    Full Text Available The current status of the nuclear data evaluation tool GENEUS (General Nuclear Data Evaluation and Uncertainty System is discussed. Especially, recent improvements of the implemented algorithms concerning smoothness and stability of the evaluated data. These modifications include an improved extrapolation algorithm for the model defect covariance matrices, the inclusion of uncertainties in level densities and charged particle optical model parameters and the employment of a regularization procedure to restore positive semidefiniteness of the prior covariance matrices. The impact of these improvements is studied for the example of neutron-induced cross sections of 55Mn for which preliminary evaluation results are also provided.

  3. NESTOR: A status report

    CERN Document Server

    Anassontzis, E G; Barone, M; Foudas, C; Grammatikakis, G; Katsanevas, S; Kourkoumelis, C; Manousakis-Katsikakis, A; Resvanis, L K; Siotis, I; Sotiriou, S A; Voulgaris, G; Minkowski, P; Grieder, P K F; Ball, A E; Bottai, S; Cartacci, A M; Monteleoni, B; Naumov, Vadim A; Trasatti, L; Fahrun, E; Keusen, U; Koske, P; Rathlev, J; Schmidt, N P; Voight, G; Bezrukov, Leonid B; Butkevich, A V; Dedenko, L G; Karaevsky, S K; Mironovich, A A; Zakharov, L M; Zheleznykh, I M; Zhukov, V A; Demidova, T A; Deineko, A O; Eremeev, A P; Paka, V T; Permyakov, A A; Platonov, M N; Rukol, V Kh; Sheremet, N A; Surin, N M; Albul, V I; Ledenev, V V

    2000-01-01

    NESTOR is an underwater neutrino astrophysics laboratory to be located in the international waters of the southwest of Greece. The first phase of this experiment is the construction and deployment of one hexagonal tower consisting of 168 optical modules, with effective are of 20000m2 for E ⩾ TeV neutrinos. Over the past few years detailed studies of the site have been carried out while many tests have been performed. The current status of the preparation of the experiment and the future plans will be presented.

  4. Status of the LHC

    CERN Document Server

    Gourber, J P

    1999-01-01

    Since the approval of the Large Hadron Collider (LHC) by the CERN Council in December 1994, considerable progress has been made in the assessment of the beam parameters and the refining of the design of the machine components and experimental areas. Thanks to the strong support from a number of countries outside the Member States, the machine will be constructed in one single stage with first physics in 2005. The first large calls for tenders are being launched. The status of the project and the future plans are presented.

  5. Status of Wheeler Reservoir

    Energy Technology Data Exchange (ETDEWEB)

    1990-09-01

    This is one in a series of status reports prepared by the Tennessee Valley Authority (TVA) for those interested in the conditions of TVA reservoirs. This overview of Wheeler Reservoir summarizes reservoir purposes and operation, reservoir and watershed characteristics, reservoir uses and use impairments, and water quality and aquatic biological conditions. The information presented here is from the most recent reports, publications, and original data available. If no recent data were available, historical data were summarized. If data were completely lacking, environmental professionals with special knowledge of the resource were interviewed. 12 refs., 2 figs.

  6. Age, relationship status, and the planning status of births

    Directory of Open Access Journals (Sweden)

    Sarah Hayford

    2010-08-01

    Full Text Available In the United States historically, births to older mothers have been more likely to be planned than births to younger mothers, and births to unmarried women have been less likely to be planned than births to married women. As the average age of mothers has increased and more births have occurred outside of marriage in the United States, the intersection of these trends may have weakened the traditional linkage between age and birth planning status. In this article, we examine differences by maternal age in planning status of births using The 2002 National Survey of Family Growth. We find that age is strongly associated with planning status, but the association is reduced in magnitude when controlling for relationship status and is stronger for first and second births than for higher-parity births. Further, the association between union status and the planning status of births varies by race-ethnicity.

  7. [The national health status].

    Science.gov (United States)

    Afek, Arnon

    2010-04-01

    During the Golden Age of Medicine (20th Century), scientific and technological breakthroughs enabled physicians to treat diseases that were previously incurable. The idealist, romantic approach of medical practice believed in the right of every human being to receive the best treatment possible, regardless of cost. However, the rise in health care expenditure at the end of the last century made this approach impossible to follow. The growing health expenses are due to the increased percentage of chronically sick patients and elderly population, costs of novel technologies and public expectations. Israel spends 7.9% of its GDP on health, a figure which has not changed in the last fifteen years, while other western countries spend a considerably higher and increasing percentage of their GDP on health. Public resources must be allocated in order to maintain the health of the population and to decrease inequities. A data-based demonstration of the population health status and health care system is therefore mandated. in this issue of the Harefuah, three articles are presented which try to show different aspects of the measurement of Israeli heath status. The data accumulated is used to improve the health status of the Israeli people. The Israel Medical Association (IMA) has assumed responsibility for the creation of an objective index for the measurement and evaluation of the public state of health and the healthcare system. The goal of the IMA National Health Index is to promote discussions regarding medicine and health in Israel, and to serve as a tool to be used by relevant policy makers. Prof. Israeli et al discuss the merits of the National Health Index as well as delineate the difficulties regarding the methodology and choice of parameters. They suggest methods for its improvement. Dr Cohen and his colleagues of Clalit Health Services present the Quality Health indicator program in the community. In effect over the past fifteen years, this program is based on

  8. Media Challenging Status Quo

    DEFF Research Database (Denmark)

    Sandvik, Kjetil

    structures and thus – along with a variety of both historical and socio-political conditions (Zizek 2011) – both enabling and shaping the protests against the financial powers of the world and their role in the global financial crisis. References: Christakis, N. & J. Fowler (2010): Connected. The amazing...... and dystopian trends in contemporary culture (Turner 2006). On that note, this paper examines the Occupy Wall Street-movement as an example on how social media may rock the status quo of today’s global power structures putting to use its democratic potential and its modes of communication through network......, New York: Perseus Books Group Rheingold, H. (2004). Smart Mobs. The Next Social Revolution. Cambridge MA: Basic Books Turner, F. (2006): From counterculture to cyberculture, University of Chicago Press. Zizek, S. (2011): “Dagen efter oprøret [The day after the riot]”, Dagbladet Information 26.10.12...

  9. Status of Advanced LIGO

    Science.gov (United States)

    Landry, Michael

    2012-10-01

    Installation of Advanced LIGO, a second-generation interferometric gravitational wave observatory, began in earnest in October of 2010. Initial LIGO instrumentation was de-installed, vacuum chambers and envelope modified, and the installation of scientific payloads begun. At LIGO Hanford Observatory, optics and suspensions comprising one of two 4km Fabry-Perot arms have been deployed and commissioned, resonating green light in an experiment to test and understand the process of controlling cavity lengths (``lock acquisition''). At LIGO Livingston, cornerstation optic and seismic isolation installation has matured such that the primary infrared laser and a suspended mode cleaner cavity (employed to spacially clean the interferometer input beam) are locked and under commissioning test. In this talk we present the status of Advanced LIGO installation and integration, and sketch the promising future of gravitational wave observation and astronomy.

  10. Status of Standardization Projects

    Science.gov (United States)

    1991-12-31

    PENTAERYTHRITOL MB DM F4 A 911 921 921 A MD MS 03 N C 6505 5486 A-A-XXX PENICILLIN G SUS MB DM F4 A 911 921 921 A MD MS 03 N C 6505 5489 A-A-XXX DEXAMETHASONE ... PHENYLBUTAZONE TABS MB DM H5 914 924 924 A MD MS 03 N 6605 TOTAL- 19. DELINQUENT- 4, STATUS CODES: A- 8, G- 1, Y- 0, Z- 10 6610 F119 MIL A 38138 AMP IND...921 921 A MD MS 03 N C 6505 5486 A-A-XXX PENICILLIN G SUS MB DM F4 A 911 921 921 A MD MS 03 N C 6505 5489 A-A-XXX DEXAMETHASONE SODIUM MB DM F4 A 911

  11. TAROT A status report

    CERN Document Server

    Boër, M; Bringer, M; Klotz, A H; Peignot, C; Malina, R F; Sánchez, P G; Pedersen, H J; Calvet, G; Eysseric, J; Leroy, A; Meissonier, M; Pollas, C; De Pacheco, J A F; Boër, Michel

    1997-01-01

    TAROT-1 is an automatic, autonomous ground based observatory whose primary goal is the rapid detection of the optical counterparts of cosmic gamma-ray burst sources. It will be able to begin imaging any GRB localization 8 seconds after receipt of an alert from CGRO/BATSE or HETE-2. TAROT-1 will reach the 17th V magnitude in 10 seconds, at a 10$\\sigma$ confidence level. TAROT will be able to observe GRB positions given by Beppo-SAX or RXTE, EUV transients from ALEXIS alerts, etc. TAROT will also study a wide range of secondary objectives and will feature a complete automatic data analysis system, and a powerful scheduling software. TAROT will be installed this fall on the Plateau du Calern, 1200m above sea level. We report on the status of the project.

  12. Status of French reactors

    Energy Technology Data Exchange (ETDEWEB)

    Ballagny, A. [Commissariat a l`Energie Atomique, Saclay (France)

    1997-08-01

    The status of French reactors is reviewed. The ORPHEE and RHF reactors can not be operated with a LEU fuel which would be limited to 4.8 g U/cm{sup 3}. The OSIRIS reactor has already been converted to LEU. It will use U{sub 3}Si{sub 2} as soon as its present stock of UO{sub 2} fuel is used up, at the end of 1994. The decision to close down the SILOE reactor in the near future is not propitious for the start of a conversion process. The REX 2000 reactor, which is expected to be commissioned in 2005, will use LEU (except if the fast neutrons core option is selected). Concerning the end of the HEU fuel cycle, the best option is reprocessing followed by conversion of the reprocessed uranium to LEU.

  13. ALSSAT Development Status

    Science.gov (United States)

    Yeh, H. Y. Jannivine; Brown, Cheryl B.; Jeng, Frank F.; Anderson, Molly; Ewert, Michael K.

    2009-01-01

    The development of the Advanced Life Support (ALS) Sizing Analysis Tool (ALSSAT) using Microsoft(Registered TradeMark) Excel was initiated by the Crew and Thermal Systems Division (CTSD) of Johnson Space Center (JSC) in 1997 to support the ALS and Exploration Offices in Environmental Control and Life Support System (ECLSS) design and studies. It aids the user in performing detailed sizing of the ECLSS for different combinations of the Exploration Life support (ELS) regenerative system technologies. This analysis tool will assist the user in performing ECLSS preliminary design and trade studies as well as system optimization efficiently and economically. The latest ALSSAT related publication in ICES 2004 detailed ALSSAT s development status including the completion of all six ELS Subsystems (ELSS), namely, the Air Management Subsystem, the Biomass Subsystem, the Food Management Subsystem, the Solid Waste Management Subsystem, the Water Management Subsystem, and the Thermal Control Subsystem and two external interfaces, including the Extravehicular Activity and the Human Accommodations. Since 2004, many more regenerative technologies in the ELSS were implemented into ALSSAT. ALSSAT has also been used for the ELS Research and Technology Development Metric Calculation for FY02 thru FY06. It was also used to conduct the Lunar Outpost Metric calculation for FY08 and was integrated as part of a Habitat Model developed at Langley Research Center to support the Constellation program. This paper will give an update on the analysis tool s current development status as well as present the analytical results of one of the trade studies that was performed.

  14. Biomarkers of Selenium Status

    Directory of Open Access Journals (Sweden)

    Gerald F. Combs, Jr.

    2015-03-01

    Full Text Available The essential trace element, selenium (Se, has multiple biological activities, which depend on the level of Se intake. Relatively low Se intakes determine the expression of selenoenzymes in which it serves as an essential constituent. Higher intakes have been shown to have anti-tumorigenic potential; and very high Se intakes can produce adverse effects. This hierarchy of biological activities calls for biomarkers informative at different levels of Se exposure. Some Se-biomarkers, such as the selenoproteins and particularly GPX3 and SEPP1, provide information about function directly and are of value in identifying nutritional Se deficiency and tracking responses of deficient individuals to Se-treatment. They are useful under conditions of Se intake within the range of regulated selenoprotein expression, e.g., for humans <55 μg/day and for animals <20 μg/kg diet. Other Se-biomarkers provide information indirectly through inferences based on Se levels of foods, tissues, urine or feces. They can indicate the likelihood of deficiency or adverse effects, but they do not provide direct evidence of either condition. Their value is in providing information about Se status over a wide range of Se intake, particularly from food forms. There is need for additional Se biomarkers particularly for assessing Se status in non-deficient individuals for whom the prospects of cancer risk reduction and adverse effects risk are the primary health considerations. This would include determining whether supranutritional intakes of Se may be required for maximal selenoprotein expression in immune surveillance cells. It would also include developing methods to determine low molecular weight Se-metabolites, i.e., selenoamino acids and methylated Se-metabolites, which to date have not been detectable in biological specimens. Recent analytical advances using tandem liquid chromatography-mass spectrometry suggest prospects for detecting these metabolites.

  15. Marital Status, Happiness, and Anomia.

    Science.gov (United States)

    Ryan, John

    1981-01-01

    Survey data indicates that neither marital status nor marital happiness is related to anomia. Suggests a moderately strong negative relationship exists between education and anomia with a weak negative relationship between overall life satisfaction and anomia. Results indicate socioeconomic status remains the primary determinant of anomia for most…

  16. SCIENTIFIC STATUS OF DIDACTICS

    Directory of Open Access Journals (Sweden)

    I. M. Osmolovskaya

    2014-01-01

    Full Text Available The research is aimed at scientific justification of didactics referred to the social and humanitarian field of knowledge. The author deals with the scientific character criteria (verity, inter-subjectivity, systemacity and validity taking into account different scientific rationality types (classical and nonclassical and identifying post-modernism influence on didactics. Objectives and results of research. Attempts are made to systematize the didactic knowledge and identify its components and structure. Didactic concepts are classified in accordance with its objects: teaching process by the whole, its individual components or educative process aspects that enable to form definite teaching views, studying it from the specific positions. The author singles out holistic-didactic, component and aspect concepts; and specifies the concept of didactic systems and models with its hierarchy. The author highlights the didactic knowledge increment. Apart from traditional empirical theoretical researches, the author’s attention is drawn to the academic pursuit such as a scientific project based on the didactic object specificity of the teaching process which is fully human controlled and realized and doesn’texist without human being. It is shown that basic theoretical ideas of scientific projects are itemized, concretized and enlarged during co-current educative practice, i.e. an adhesion of theory and practice occurs.It is stressed that there are two special directions of didactic development multidimensionality: 1. extension of its semantic field in the context of modern socio-cultural conditions; 2. increase of scientific status related to a conceptual framework improvement, empirically accumulated information arrangement, new hypotheses, theories and concepts’ development. Scientific novelty. The research findings demonstrate well-reasoned statement of the didactics’ scientific status, its particular components and structure

  17. TESLA Test Facility. Status

    Energy Technology Data Exchange (ETDEWEB)

    Aune, B. [Deutsches Elektronen-Synchrotron (DESY), Hamburg (Germany); TESLA Collaboration

    1996-01-01

    The TESLA Test Facility (TTF), under construction at DESY by an international collaboration, is an R and D test bed for the superconducting option for future linear e+/e-colliders. It consists of an infrastructure to process and test the cavities and of a 500 MeV linac. The infrastructure has been installed and is fully operational. It includes a complex of clean rooms, an ultra-clean water plant, a chemical etching installation and an ultra-high vacuum furnace. The linac will consist of four cryo-modules, each containing eight 1 meter long nine-cell cavities operated at 1.3 GHz. The base accelerating field is 15 MV/m. A first injector will deliver a low charge per bunch beam, with the full average current (8 mA in pulses of 800 {mu}s). A more powerful injector based on RF gun technology will ultimately deliver a beam with high charge and low emittance to allow measurements necessary to qualify the TESLA option and to demonstrate the possibility of operating a free electron laser based on the Self-Amplified-Spontaneous-Emission principle. Overview and status of the facility will be given. Plans for the future use of the linac are presented. (R.P.). 19 refs.

  18. ANAIS: Status and prospects

    CERN Document Server

    Amaré, Julio; Cuesta, Clara; García, Eduardo; Ginestra, Carlos; Martínez, María; Oliván, Miguel A; Ortigoza, Ysrael; de Solórzano, Alfonso Ortíz; Pobes, Carlos; Puimedón, Jorge; Sarsa, María Luisa; Villar, José Ángel; Villar, Patricia

    2015-01-01

    ANAIS experiment will look for dark matter annual modulation with large mass of ultra-pure NaI(Tl) scintillators at the Canfranc Underground Laboratory (LSC), aiming to confirm the DAMA/LIBRA positive signal in a model-independent way. Two 12.5 kg each NaI(Tl) crystals provided by Alpha Spectra are currently taking data at the LSC. Present status of ANAIS detectors background and general performance is summarized; in particular, thanks to the high light collection efficiency prospects of lowering the threshold down to 1 keVee are reachable. Crystal radiopurity goals are fulfilled for $^{232}$Th and $^{238}$U chains and $^{40}$K activity, although higher than original goal, could be accepted; however, high $^{210}$Pb contamination out-of-equilibrium has been identified. More radiopure detectors are being built by Alpha Spectra. The ongoing high quantum efficiency PMT tests and muon veto characterization are also presented. Finally, the sensitivity of the experiment for the annual modulation in the WIMP signal,...

  19. MARS: a status report

    Energy Technology Data Exchange (ETDEWEB)

    Tribble, R.E.; Gagliardi, C.A.; Liu, W. (Cyclotron Inst., Texas A and M Univ., College Station (USA))

    1991-05-01

    We are building a momentum achromat recoil spectrometer (MARS) for use with the new K500 superconducting cyclotron at Texas A and M University. MARS uses a unique optical design utilizing two dispersive planes to combine a momemtum achromat with a recoil mass spectrometer. This configuration makes MARS applicable to a broad range of nuclear reaction studies utilizing inverse kinematics. It also leads to a system that is well matched to the range of secondary particle energies that will be produced in reactions with K500 beam. MARS will have a typical mass resolution of {delta}M/M{approx equal}1/300, with an energy acceptance of {+-}9% {Delta}E/E and a geometric solid angle of up to 9 msr. A beam swinger system will alow reaction products in the angular range 0deg to 30deg to be studied. MARS will be used to study both the excited states and decay properties of very proton- and neutron-rich nuclei. MARS will also be used to provide a reaction mechanism filter to assist investigations of the dynamics of heavy ion collisions and to produce secondary radioactive beams for reaction and spectroscopic studies of particular interest for nuclear astrophysics. We briefly describe the design of MARS, give a status report on its construction and an overview of the scientific program planned for it. (orig.).

  20. Biosimilar drugs: Current status.

    Science.gov (United States)

    Kumar, Rajiv; Singh, Jagjit

    2014-07-01

    Biologic products are being developed over the past three decades. The expiry of patent protection for many biological medicines has led to the development of biosimilars in UK or follow on biologics in USA. This article reviews the literature on biosimilar drugs that covers the therapeutic status and regulatory guidelines. Appraisal of published articles from peer reviewed journals for English language publications, search from PubMed, and guidelines from European Medicines Agency, US Food Drug Administration (FDA) and India were used to identify data for review. Literature suggest that biosimilars are similar biological products, i.e., comparable but not identical to the reference product, are not generic version of innovator product and do not ensure therapeutic equivalence. Biosimilars present more challenges than conventional generics and marketing approval is also more complicated. To improve access, US Congress passed the Biologics Price Competition and Innovation act 2009 and US FDA allowed "abbreviated pathway" for their approval. U.S law has defined new standards and terms and EMA scientific guidelines have also set detailed approval standards. India being one of the most preferred manufacturing destinations of biosimilars, there is a need for stringent safety and regulatory guidelines. The New India Guidelines "Draft Guidelines on Similar Biologics were announced in June 2012, by Department of Biotechnology at Boston bio and available online.

  1. Status of VIRGO

    CERN Document Server

    Freise, A; Amico, P; Arnaud, N; Avino, S; Babusci, D; Barille, R; Barone, F; Barsotti, L; Barsuglia, M; Beauville, F; Bizouard, M A; Boccara, C; Bondu, F; Bosi, L; Bradaschia, C; Braccini, S; Brillet, A; Brisson, V; Brocco, L; Buskulic, Damir; Calamai, G; Calloni, E; Campagna, E; Cavalier, F; Cella, G; Chassande-Mottin, E; Cleva, F; Cokelaer, T; Coulon, J P; Cuoco, E; Dattilo, V; Davier, M; De Rosa, R; Di Fiore, L; Di Virgilio, A; Dujardin, B; Eleuteri, A; Enard, D; Ferrante, I; Fidecaro, F; Fiori, I; Flaminio, R; Fournier, J D; Frasca, S; Frasconi, F; Gammaitoni, L; Gennai, A; Giazotto, A; Giordano, G; Giordano, L; Guidi, G; Heitmann, H; Hello, P; Heusse, P; Holloway, L; Kreckelbergh, S; La Penna, P; Loriette, V; Loupias, M; Losurdo, G; Mackowski, J M; Majorana, E; Man, C N; Marchetti, E; Marion, F; Martelli, F; Masserot, A; Massonnet, Louis; Mazzoni, M; Milano, L; Moreau, J; Moreau, F; Morgado, N; Mornet, F; Mours, B; Pacheco, J; Pai, A; Palomba, C; Paoletti, F; Pardi, S; Passaquieti, R; Passuello, D; Perniola, B; Pinard, L; Poggiani, R; Punturo, M; Puppo, P; Qipiani, K; Ramonet, J; Rapagnani, P; Reita, V; Remillieux, A; Ricci, F; Ricciardi, I; Russo, G; Solimeno, S; Stanga, R; Tournefier, E; Travasso, F; Trinquet, H; Verkindt, D; Vetrano, F; Veziant, O; Viceré, A; Vinet, J Y; Vocca, H; Yvert, M

    2003-01-01

    The French-Italian interferometric gravitational wave detector VIRGO is currently being commissioned. Its principal instrument is a Michelson interferometer with 3 km long optical cavities in the arms and a power-recycling mirror. This paper gives an overview of the present status of the system. We report on the presently attained sensitivity and the system's performance during the recent commissioning runs. After a sequence of intermediate stages, the interferometer is now being used in the so-called recombined configuration. The input laser beam is spatially filtered by a 144 m long input mode-cleaner before being injected to the main interferometer. The main optics are suspended from so-called \\sa s, which provide an excellent seismic isolation. The two 3 km long Fabry-Perot arm cavities are kept in resonance with the laser light, and the Michelson interferometer is held on the dark fringe. An automatic mirror alignment system based on the Anderson technique has been implemented for the arm cavities. The l...

  2. Treatment of Established Status Epilepticus

    Science.gov (United States)

    Falco-Walter, Jessica J.; Bleck, Thomas

    2016-01-01

    Status epilepticus is the most severe form of epilepsy, with a high mortality rate and high health care costs. Status epilepticus is divided into four stages: early, established, refractory, and super-refractory. While initial treatment with benzodiazepines has become standard of care for early status epilepticus, treatment after benzodiazepine failure (established status epilepticus (ESE)) is incompletely studied. Effective treatment of ESE is critical as morbidity and mortality increases dramatically the longer convulsive status epilepticus persists. Phenytoin/fosphenytoin, valproic acid, levetiracetam, phenobarbital, and lacosamide are the most frequently prescribed antiseizure medications for treatment of ESE. To date there are no class 1 data to support pharmacologic recommendations of one agent over another. We review each of these medications, their pharmacology, the scientific evidence in support and against each in the available literature, adverse effects and safety profiles, dosing recommendations, and limitations of the available evidence. We also discuss future directions including the established status epilepticus treatment trial (ESETT). Substantial further research is urgently needed to identify these patients (particularly those with non-convulsive status epilepticus), elucidate the most efficacious antiseizure treatment with head-to-head randomized prospective trials, and determine whether this differs for convulsive vs. non-convulsive ESE. PMID:27120626

  3. Treatment of Established Status Epilepticus

    Directory of Open Access Journals (Sweden)

    Jessica J. Falco-Walter

    2016-04-01

    Full Text Available Status epilepticus is the most severe form of epilepsy, with a high mortality rate and high health care costs. Status epilepticus is divided into four stages: early, established, refractory, and super-refractory. While initial treatment with benzodiazepines has become standard of care for early status epilepticus, treatment after benzodiazepine failure (established status epilepticus (ESE is incompletely studied. Effective treatment of ESE is critical as morbidity and mortality increases dramatically the longer convulsive status epilepticus persists. Phenytoin/fosphenytoin, valproic acid, levetiracetam, phenobarbital, and lacosamide are the most frequently prescribed antiseizure medications for treatment of ESE. To date there are no class 1 data to support pharmacologic recommendations of one agent over another. We review each of these medications, their pharmacology, the scientific evidence in support and against each in the available literature, adverse effects and safety profiles, dosing recommendations, and limitations of the available evidence. We also discuss future directions including the established status epilepticus treatment trial (ESETT. Substantial further research is urgently needed to identify these patients (particularly those with non-convulsive status epilepticus, elucidate the most efficacious antiseizure treatment with head-to-head randomized prospective trials, and determine whether this differs for convulsive vs. non-convulsive ESE.

  4. Therapie des Status epilepticus

    Directory of Open Access Journals (Sweden)

    Trinka E

    2009-01-01

    Full Text Available Der Status epilepticus (SE ist nach dem Schlaganfall der häufigste neurologische Notfall. Er stellt als generaliserter konvulsiver SE (GKSE die schwerste Ausprägung eines epileptischen Anfalls dar, der mit einer signifikanten Morbidität und einer ca. 20%igen Letalität verbunden ist. Nur bei der Hälfte der Patienten mit SE besteht zuvor eine Epilepsie; die meisten Fälle sind symptomatisch, wobei Schädel- Hirn-Traumata, zerebrovaskuläre Erkrankungen, ZNS-Infektionen und metabolische Ursachen führend sind. Bei Patienten mit vorbestehender Epilepsie lässt sich eine frühe Phase des GKSE erkennen, in der die Anfälle crescendoartig zunehmen, bis sie in kontinuierliche Anfallsaktivität münden (etablierte Phase. Das Management eines GKSE verlangt rasches und beherztes Vorgehen. Neben der sofort einzuleitenden Therapie muss gleichzeitig die artdiagnostische Zuordnung des SE und die Ursache erkannt und behandelt werden. Als Therapie der ersten Wahl sind Benzodiazepine etabliert, wobei intravenösem (i.v. Lorazepam gegenüber Diazepam der Vorzug zu geben ist. Versagt die Therapie mit Benzodiazepinen, muss rasch und konsequent nach einem Stufenschema vorgegangen werden. Phenytoin/Fosphenytoin, Valproinsäure, Levetiracetam und Lacosamid sind als i.v. Formulierung erhältliche Antiepileptika. Obwohl Vergleichsstudien hier fehlen, wird Phenytoin bevorzugt. Valproat und Levetiracetam sind nicht sedierend und kardiovaskulär gut verträglich, sodass hier Alternativen zu Phenytoin vorhanden sind. Lacosamid ist eine neue Therapieoption, deren Stellenwert erst bestimmt werden muss. Versagt auch die zweite Therapiestufe, so muss der Patient intubiert und in Allgemeinanästhesie intensivmedizinisch behandelt werden. Dafür stehen Thiopental, Propofol oder hoch dosiertes Midazolam zu Verfügung. Durch den eklatanten Mangel an randomisierten Studien bleibt die Therapie des GKSE empirisch und durch den Off-label-Einsatz gekennzeichnet.

  5. Current status of pulmonary metastasectomy

    DEFF Research Database (Denmark)

    Hornbech, Kåre; Ravn, Jesper; Steinbrüchel, Daniel Andreas

    2011-01-01

    for unresected patients. In this article, we discuss the current status on pulmonary metastasectomy. Preoperative assessment and selection of surgical candidates is covered. The different surgical strategies including surgical approach, unilateral versus bilateral exploration, lymph node dissection, and repeat...

  6. Refugee status determination: three challenges

    Directory of Open Access Journals (Sweden)

    Martin Jones

    2009-04-01

    Full Text Available Refugee status determination (RSD, which is vital to the protection of so many asylum seekers worldwide, is at best an imperfect, haphazard and challenging process. It merits greater attention and appropriate reform.

  7. Socioeconomic Status, IQ, and Delinquency.

    Science.gov (United States)

    Moffitt, Terrie E.; And Others

    1981-01-01

    Results from two Danish prospective longitudinal studies are presented to support the view that IQ bears a causal relationship to delinquency that is independent of the effects of socioeconomic status (SES). (CL)

  8. Coagulation Status in Hidradenitis Suppurativa

    DEFF Research Database (Denmark)

    Miller, Iben Marie; Johansen, Maria Egede; Mogensen, Ulla B

    2015-01-01

    BACKGROUND: Chronic inflammatory diseases other than hidradenitis suppurativa (HS) have been associated with prothrombotic/hypercoagulable status. OBJECTIVE: To investigate a possible association between the chronic inflammatory skin disease HS and prothrombotic/hypercoagulable state. METHODS: We...

  9. Sentinel-2 Mission status

    Science.gov (United States)

    Hoersch, Bianca; Colin, Olivier; Gascon, Ferran; Arino, Olivier; Spoto, Francois; Marchese, Franco; Krassenburg, Mike; Koetz, Benjamin

    2016-04-01

    Copernicus is a joint initiative of the European Commission (EC) and the European Space Agency (ESA), designed to establish a European capacity for the provision and use of operational monitoring information for environment and security applications. Within the Copernicus programme, ESA is responsible for the development of the Space Component, a fully operational space-based capability to supply earth-observation data to sustain environmental information Services in Europe. The Sentinel missions are Copernicus dedicated Earth Observation missions composing the essential elements of the Space Component. In the global Copernicus framework, they are complemented by other satellites made available by third-parties or by ESA and coordinated in the synergistic system through the Copernicus Data-Access system versus the Copernicus Services. The Copernicus Sentinel-2 mission provides continuity to services relying on multi-spectral high-resolution optical observations over global terrestrial surfaces. Sentinel-2 capitalizes on the technology and the vast experience acquired in Europe and the US to sustain the operational supply of data for services such as forest monitoring, land cover changes detection or natural disasters management. The Sentinel-2 mission offers an unprecedented combination of the following capabilities: ○ Systematic global coverage of land surfaces: from 56°South to 84°North, coastal waters and Mediterranean sea; ○ High revisit: every 5 days at equator under the same viewing conditions with 2 satellites; ○ High spatial resolution: 10m, 20m and 60m; ○ Multi-spectral information with 13 bands in the visible, near infra-red and short wave infra-red part of the spectrum; ○ Wide field of view: 290 km. The data from the Sentinel-2 mission are available openly and freely for all users with online easy access since December 2015. The presentation will give a status report on the Sentinel-2 mission, and outlook for the remaining ramp-up Phase, the

  10. Enhance the Team Status Meeting

    Science.gov (United States)

    2014-12-01

    collection and analysis tool chosen by the team : the Process Dashboard © 1998-2014 Tuma Solutions, LLC. Using this format , the PRT teams are now getting...status meetings of those teams coached by the NAVAIR PRT have evolved into more relevant, easier to understand, and more visually interesting formats ...support, this submission to Open Forum highlights the team status meeting. These meetings help keep a team aware, engaged, and on-track. Their content

  11. Status report, canister fabrication

    Energy Technology Data Exchange (ETDEWEB)

    Andersson, Claes-Goeran; Eriksson, Peter; Westman, Marika [Swedish Nuclear Fuel and Waste Management Co., Stockholm (Sweden); Emilsson, Goeran [CSM Materialteknik AB, Linkoeping (Sweden)

    2004-06-01

    The report gives an account of the development of material and fabrication technology for copper canisters with cast inserts during the period from 2000 until the start of 2004. The engineering design of the canister and the choice of materials in the constituent components described in previous status reports have not been significantly changed. In the reference canister, the thickness of the copper shell is 50 mm. Fabrication of individual components with a thinner copper thickness is done for the purpose of gaining experience and evaluating fabrication and inspection methods for such canisters. As a part of the development of cast inserts, computer simulations of the casting processes and techniques used at the foundries have been performed for the purpose of optimizing the material properties. These properties have been evaluated by extensive tensile testing and metallographic inspection of test material taken from discs cut at different points along the length of the inserts. The testing results exhibit a relatively large spread. Low elongation values in certain tensile test specimens are due to the presence of poorly formed graphite, porosities, slag or other casting defects. It is concluded in the report that it will not be possible to avoid some presence of observed defects in castings of this size. In the deep repository, the inserts will be exposed to compressive loading and the observed defects are not critical for strength. An analysis of the strength of the inserts and formulation of relevant material requirements must be based on a statistical approach with probabilistic calculations. This work has been initiated and will be concluded during 2004. An initial verifying compression test of a canister in an isostatic press has indicated considerable overstrength in the structure. Seamless copper tubes are fabricated by means of three methods: extrusion, pierce and draw processing, and forging. It can be concluded that extrusion tests have revealed a

  12. Social Carrying Capacity as Status Group Convention.

    Science.gov (United States)

    West, Patrick C.

    A sociological study investigating the relationship between perception of crowding and social status was conducted in a rural camping setting. Results indicate that higher social status groups and groups aspiring to higher social status are more likely to perceive crowding than are lower status groups, but more research is suggested prior to the…

  13. ANTIOXIDANT STATUS IN DIABETIC NEPHROPATHY

    Directory of Open Access Journals (Sweden)

    Giriraja

    2015-12-01

    Full Text Available BACKGROUND Hyperglycemia and dislipidemia in DM induce increased lipid peroxdation and free radical formation. This is an important mechanism of microangiopathy. AIM To measure the antioxidant status in type 2 DM with nephropathy and compared with nondiabetic control group. MATERIALS AND METHODS 50 type 2 DM patients aged between 50 to 70 years according to national diabetes data group criteria with nephropathy diagnosed on the basis of history, physical examination and biochemical parameters were included. 50 age and sex matched apparently healthy individuals with normal plasma glucose, normal renal parameters and with no symptoms suggestive of DM were taken as controls. RESULTS Antioxidant status was significantly less in patients with diabetic nephropathy. CONCLUSION Data suggests that alteration in antioxidant status may help predict the risk of diabetic nephropathy.

  14. The treatment of status epilepticus.

    Science.gov (United States)

    Riviello, James J; Holmes, Gregory L

    2004-06-01

    Status epilepticus (SE) is a life-threatening emergency that requires prompt treatment, including basic neuroresuscitation principles (the ABCs), antiepileptic drugs to stop the seizure, and identification of etiology. Symptomatic SE is more common in younger children. Treating the precipitating cause may prevent ongoing neurologic injury and facilitates seizure control. A systematic treatment regimen, planned in advance, is needed, including one for refractory status epilepticus (RSE). Here we emphasize definitions, clinical and electroencephalography stages, early treatment, special circumstances that may require immediate seizure control, and treatment of RSE. Because much clinical research in SE has been done in adults, we indicate the patient population studied.

  15. Risk factors for brain metastases in patients with metastatic colorectal cancer

    DEFF Research Database (Denmark)

    Christensen, Troels Dreier; Palshof, Jesper Andreas; Larsen, Finn Ole

    2017-01-01

    patients had previously progression on 5-FU, irinotecan and oxaliplatin containing regimens and received CetIri treatment independent of RAS mutations status. We subsequently performed KRAS, NRAS, BRAF, PIK3CA, PTEN, ERBB2 and EGFR sequencing of DNA extracted from primary tumor tissue. Results: Totally...

  16. The Role of Novel Substituted Diindolyl Methane Analogues in the Treatment of Triple-Negative and ErbB2-Positive Breast Cancer

    Science.gov (United States)

    2015-05-01

    apoptosis, inflammatory responses, regulation of the hypothalamic-pituitary axis (HPA) and reproductive processes [59]. Additionally, NR4A2 plays a...Ligand-independent actions of the orphan receptors/ corepressors DAX-1 and SHP in metabolism, reproduction and disease, J. Steroid Biochem. Mol. Biol. 130...formation, Brain Res. Bull . 85 (2011) 21–29. [79] N. Volakakis, B. Kadkhodaei, E. Joodmardi, K. Wallis, L. Panman, J. Silvaggi, B. M. Spiegelman, T

  17. Final overall survival analysis of a phase II trial evaluating vinorelbine and lapatinib in women with ErbB2 overexpressing metastatic breast cancer.

    Science.gov (United States)

    Janni, Wolfgang; Sarosiek, Tomasz; Karaszewska, Boguslawa; Pikiel, Joanna; Staroslawska, Elzbieta; Potemski, Piotr; Salat, Christoph; Brain, Etienne; Caglevic, Christian; Briggs, Kathryn; Mahood, Kim; DeSilvio, Michelle; Marini, Luca; Papadimitriou, Christos

    2015-12-01

    Lapatinib plus capecitabine (lap+cap) is approved as treatment for patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC), who have progressed on prior trastuzumab in the metastatic setting. We previously reported progression-free survival (PFS), overall survival (OS) and safety results from this open-label, multicentre, phase II study (VITAL; NCT01013740) conducted in women with HER2 positive MBC, to evaluate the efficacy and safety of lap plus vinorelbine (lap+vin), an important chemotherapy option for MBC, compared with lap+cap. In total, 112 patients were randomised 2:1 to treatment with lap+vin (N = 75) or lap+cap (N = 37). Results showed that the median PFS (primary endpoint) and OS (secondary endpoint) post-randomisation were comparable between treatment arms, with no new safety signals detected. Here, we assessed the final OS in this study at 40 months post-randomisation. At the time of final analyses, 24 (32%) patients were ongoing in the lap+vin arm, compared with 14 (38%) patients in the lap+cap arm (92% in both arms had discontinued treatment). Median OS in the lap+vin arm was 23.3 months (95% confidence intervals [CI]: 18.5, 31.1), compared with 20.3 months (95% CI: 16.4, 31.8) in the lap+cap arm. The median follow-up in the lap+vin arm was 18.86 months (95% CI: 10.68, 26.02), compared with 19.38 (95% CI: 25.56) months in the lap+cap arm. Similar rates of death (56-57%) were observed in both arms. The final OS was consistent with the previously reported data and suggest that lap+vin offers an effective treatment option for women with HER2-positive MBC.

  18. ErbB4 Overexpression as an Antagonist of ErbB2/HER2/Neu Induced Human Breast Cancer Cell Proliferation

    Science.gov (United States)

    2006-08-01

    BH3-only proteins, including BID, BIM, BIK, HRK, NOXA , and PUMA, share a single BH3 domain that is essential for cell-killing activity. They are...BH3-only proteins, including BIM, HRK, BBC3, NOXA , and PUMA, are transcriptionally regulated, whereas the apoptotic activities of BID, BAD, and BIK

  19. Localisation Microscopy of Breast Epithelial ErbB-2 Receptors and Gap Junctions: Trafficking after γ-Irradiation, Neuregulin-1β, and Trastuzumab Application

    Science.gov (United States)

    Pilarczyk, Götz; Nesnidal, Ines; Gunkel, Manuel; Bach, Margund; Bestvater, Felix; Hausmann, Michael

    2017-01-01

    In cancer, vulnerable breast epithelium malignance tendency correlates with number and activation of ErbB receptor tyrosine kinases. In the presented work, we observe ErbB receptors activated by irradiation-induced DNA injury or neuregulin-1β application, or alternatively, attenuated by a therapeutic antibody using high resolution fluorescence localization microscopy. The gap junction turnover coinciding with ErbB receptor activation and co-transport is simultaneously recorded. DNA injury caused by 4 Gray of 6 MeV photon γ-irradiation or alternatively neuregulin-1β application mobilized ErbB receptors in a nucleograde fashion—a process attenuated by trastuzumab antibody application. This was accompanied by increased receptor density, indicating packing into transport units. Factors mobilizing ErbB receptors also mobilized plasma membrane resident gap junction channels. The time course of ErbB receptor activation and gap junction mobilization recapitulates the time course of non-homologous end-joining DNA repair. We explain our findings under terms of DNA injury-induced membrane receptor tyrosine kinase activation and retrograde trafficking. In addition, we interpret the phenomenon of retrograde co-trafficking of gap junction connexons stimulated by ErbB receptor activation. PMID:28208769

  20. Cooperación oncogénica entre la citoquina pro-inflamatoria SP y el receptor tirosina quinasa ErbB-2/HER2

    OpenAIRE

    Garcia Recio, Susana

    2012-01-01

    INTRODUCCIÓN: La inflamación es un sello distintivo del cáncer. La inflamación crónica está fuertemente relacionada con el desarrollo y la progresión tumoral y suministra al tumor múltiples citoquinas proinflamatorias que pueden modular la señalización de la célula tumoral. Este es el caso de la Sustancia P (SP), una citoquina pro-inflamatoria/neuropéptido presente en el microambiente tumoral perteneciente a la familia de las taquiquininas y que señaliza principalmente a través de su receptor...

  1. Domain Specific Effects of Herstatin, an Alternative HER-2 (erbB-2) Product, on erbB Positive Breast Cancer

    Science.gov (United States)

    2006-05-01

    53. Sambrook, J., Maniatis , T., and Fritsch, E. F. (1989) Molecular cloning : a laboratory manual, 2nd Ed., Cold Spring Harbor Laboratory, Cold Spring...of HER-2 is a common molecular abnormality in breast cancer, implicated in 20 - 30% of all cases(6). HER-2 is the preferred heterodimer partner of...its efficacy is limited to a subset of HER-2 overexpressing breast tumors, and its molecular mechanism is poorly understood. This points to the great

  2. The Medicina Station Status Report

    Science.gov (United States)

    Orfei, Alessandro; Orlati, Andrea; Maccaferri, Giuseppe

    2013-01-01

    General information about the Medicina Radio Astronomy Station, the 32-m antenna status, and the staff in charge of the VLBI observations is provided. In 2012, the data from geodetic VLBI observations were acquired using the Mark 5A recording system with good results. Updates of the hardware were performed and are briefly described.

  3. The status of cold fusion

    Science.gov (United States)

    Storms, E.

    This report attempts to update the status of the phenomenon of cold fusion. The new field is continuing to grow as a variety of nuclear reactions are discovered to occur in a variety of chemical environments at modest temperatures. However, it must be cautioned that most scientists consider cold fusion as something akin to UFO's, ESP, and numerology.

  4. Targeted Advertising and Social Status

    NARCIS (Netherlands)

    N. Vikander (Nick)

    2010-01-01

    textabstractThis paper shows how a firm can use non-targeted advertising to exploit consumers' desire for social status. A monopolist sells multiple varieties of a good to consumers who each care about what others believe about his wealth. Advertising allows consumers both to buy different varieties

  5. Present status of processing method

    Energy Technology Data Exchange (ETDEWEB)

    Kosako, Kazuaki [Sumitomo Atomic Energy Industries Ltd., Tokyo (Japan)

    1998-11-01

    Present status of processing method for a high-energy nuclear data file was examined. The NJOY94 code is the only one available to the processing. In Japan, present processing used NJOY94 is orienting toward the production of traditional cross section library, because a high-energy transport code using a high-energy cross section library is indistinct. (author)

  6. Status of spallation neutron source

    Energy Technology Data Exchange (ETDEWEB)

    Oyama, Yukio [Japan Atomic Energy Research Inst., Tokai, Ibaraki (Japan). Tokai Research Establishment

    1997-03-01

    Existing and planned facilities using proton accelerator driven spallation neutron source are reviewed. These include new project of neutron science proposed from Japan Atomic Energy Research Institute. The present status of facility requirement and accelerator technology leads us to new era of neutron science such as neutron scattering research and nuclear transmutation study using very intense neutron source. (author)

  7. NIE Planning Status, July 1972.

    Science.gov (United States)

    Silberman, Harry F.

    This paper summarizes the current status of the National Institute of Education (NIE) plans for programs and organization as of the beginning of the 1973 fiscal year. The author considers the purpose of NIE as outlined in the NIE enabling legislation, lists the goals of education, and examines the problems that arise in trying to achieve those…

  8. Status of Fermilab E-710

    Energy Technology Data Exchange (ETDEWEB)

    Rubinstein, R.; E-710 Collaboration

    1993-08-01

    This report give the current status of E-710, an experiment at the Fermilab {bar p}p Tevatron Collider to measure elastic scattering, total cross sections and diffraction dissociation up to {radical}s = 1.8 TeV.

  9. Ivory Coast: Country Status Report.

    Science.gov (United States)

    Bruhn, Thea C.

    A survey of the status of language usage in the Ivory Coast begins with an overview of the usage patterns of French, the official language, and the five most commonly used native languages: Jula, Anyi-Baoule, Senoufo, Bete, and Dan. Recent Ivorian efforts at language planning, development, and research are also highlighted. A matrix follows that…

  10. European Solar Telescope: Progress status

    NARCIS (Netherlands)

    Collados, M.; Bettonvil, F.C.M.; Cavaller, L.; Ermolli, I.; Gelly, B.; Pérez, A.; Socas-Navarro, H.; Soltau, D.; Volkmer, R.

    2010-01-01

    In this paper, the present status of the development of the design of the European Solar Telescope is described. The telescope is devised to have the best possible angular resolution and polarimetric performance, maximizing the throughput of the whole system. To that aim, adaptive optics and multi-c

  11. IEC Research Status at MSFC

    Science.gov (United States)

    Hrbud, Ivana; Dobson, Chris

    2001-01-01

    This viewgraph presentation gives an overview of the Inertial Electrostatic Confinement (IEC) research status at Marshall Space Flight Center. Details are given on the experiment setup (hardware characteristics, diagnostic equipment, propellant feed system, and planned pulse mode operation), grid manufacturing (identified manufacturing techniques, such as metal deposition, negative template mold, and machining), and grid for IEC operation (negative template technique and electrochemical technique).

  12. Status over revisionforskningen i Danmark

    DEFF Research Database (Denmark)

    Seehausen, Jesper; Holm, Claus

    Aalborg Universitet og lektor, ph.d. Claus Holm fra Handelshøjskolen i Århus status over revisionsforskningen i Danmark. Der fokuseres på den forskning, som gennemføres og publiceres i form af ph.d.-afhandlinger. Således giver forfatterne blandt andet en oversigt over indholdet i de hidtidige danske ph...

  13. Ownership as a Social Status

    Science.gov (United States)

    Kalish, Charles W.; Anderson, Craig D.

    2011-01-01

    The authors suggest that ownership may be one of the critical entry points into thinking about social constructions, a kind of laboratory for understanding status. They discuss the features of ownership that make it an interesting case to study developmentally. In particular, ownership is a consequential social fact that is alterable by an…

  14. 2010 Chemical Working Group Status

    Science.gov (United States)

    Reid, Concha M.

    2010-01-01

    The Steering Group for the Interagency Advanced Power Group (IAPG) held their business meeting on November 30-December 1st in McLean, Virginia. Status reports were presented from each of the IAPG's Working Groups. These charts contain a brief summary of the IAPG Chemical Working Group's activities during 2010 and its plans for 2011.

  15. Status of the QCDOC project

    CERN Document Server

    Boyle, P A; Christ, N H; Cristian, C; Dong, Z; Gara, A; Joó, B; Kim, C; Levkova, L; Liao, X; Liu, G; Mawhinney, Robert D; Ohta, S; Wettig, T; Yamaguchi, A

    2002-01-01

    A status report is given of the QCDOC project, a massively parallel computer optimized for lattice QCD using system-on-a-chip technology. We describe several of the hardware and software features unique to the QCDOC architecture and present performance figures obtained from simulating the current VHDL design of the QCDOC chip with single-cycle accuracy.

  16. The Epistemic Status of Intelligence

    DEFF Research Database (Denmark)

    Rønn, Kira Vrist; Høffding, Simon

    2012-01-01

    We argue that the majority of intelligence definitions fail to recognize that the normative epistemic status of intelligence is knowledge and not an inferior alternative. We refute the counter-arguments that intelligence ought not to be seen as knowledge because of 1) its action-oriented scope...... and robustness of claims to intelligence-knowledge can be assessed....

  17. Ethiopia: Country Status Report (Revision).

    Science.gov (United States)

    McFerren, Margaret

    A survey of the status of language usage in Ethiopia begins with an overview of the distribution of Amharic, the sole official language and medium of elementary instruction, and Tigrinya, Oromo, Wolayto, Somali, Sidamo, Hadiyya, and English, the medium of secondary and higher education instruction. The relationship of language usage patterns to…

  18. Reducing status quo bias in choice experiments

    DEFF Research Database (Denmark)

    Bonnichsen, Ole; Ladenburg, Jacob

    2015-01-01

    to be superior, i.e. a status quo effect. However, in the stated preference literature, the tendency to choose the alternative representing the status quo situation seems to exceed real life status quo effects. Accordingly, status quo bias can be a problem. In the Choice Experiment literature, status quo bias...... is found to be a function of protest attitudes concerning the payment of the hypothetical good. In a split sample framework we test an ex-ante entreaty aimed at reducing payment based protest attitudes. We find that the entreaty reduces status quo bias and improves the internal validity of stated...

  19. STATUS TAKSONOMI, DISTRIBUSI DAN KATEGORI STATUS KONSERVASI MAGNOLIACEAE DI INDONESIA

    Directory of Open Access Journals (Sweden)

    Andes Hamuraby Rozak

    2012-07-01

    Full Text Available The Family of Magnoliaceae is one of the most primitive taxa in the world.  Knowledge of this family is essential for studies on the origin, evolution and systematics of Angiosperms.  There are 223 species belongs to this family in the world and 25 of them are found in Indonesia. This paper explains taxonomy, distribution, and conservation status of the family Magnoliaceae in Indonesia.

  20. Why do nominal characteristics acquire status value? A minimal explanation for status construction.

    Science.gov (United States)

    Mark, Noah P; Smith-Lovin, Lynn; Ridgeway, Cecilia L

    2009-11-01

    Why do beliefs that attach different amounts of status to different categories of people become consensually held by the members of a society? We show that two microlevel mechanisms, in combination, imply a system-level tendency toward consensual status beliefs about a nominal characteristic. (1) Status belief diffusion: a person who has no status belief about a characteristic can acquire a status belief about that characteristic from interacting with one or more people who have that status belief. (2) Status belief loss: a person who has a status belief about a characteristic can lose that belief from interacting with one or more people who have the opposite status belief. These mechanisms imply that opposite status beliefs will tend to be lost at equal rates and will tend to be acquired at rates proportional to their prevalence. Therefore, if a status belief ever becomes more prevalent than its opposite, it will increase in prevalence until every person holds it.

  1. Nonconvulsive status epilepticus after electroconvulsive therapy

    DEFF Research Database (Denmark)

    Povlsen, Uffe Juul; Wildschiødtz, Gordon; Høgenhaven, Hans;

    2003-01-01

    SUMMARY: We describe three cases of nonconvulsive status epilepticus induced by electroconvulsive therapy (ECT). Nonconvulsive status epilepticus is an important differential diagnosis in patients who develop prolonged confusion after ECT. The present cases exemplify the difficulty in defining...

  2. Nonconvulsive status epilepticus disguising as hepatic encephalopathy.

    Science.gov (United States)

    Jo, Yong Min; Lee, Sung Wook; Han, Sang Young; Baek, Yang Hyun; Ahn, Ji Hye; Choi, Won Jong; Lee, Ji Young; Kim, Sang Ho; Yoon, Byeol A

    2015-04-28

    Nonconvulsive status epilepticus has become an important issue in modern neurology and epileptology. This is based on difficulty in definitively elucidating the condition and its various clinical phenomena and on our inadequate insight into the intrinsic pathophysiological processes. Despite nonconvulsive status epilepticus being a situation that requires immediate treatment, this disorder may not be appreciated as the cause of mental status impairment. Although the pathophysiology of nonconvulsive status epilepticus remains unknown, this disorder is thought to lead to neuronal damage, so its identification and treatment are important. Nonconvulsive status epilepticus should be considered in the differential diagnosis of patients with liver cirrhosis presenting an altered mental status. We report a case of a 52-year-old male with liver cirrhosis presenting an altered mental status. He was initially diagnosed with hepatic encephalopathy but ultimately diagnosed with nonconvulsive status epilepticus by electroencephalogram.

  3. US Forest Service Land Status and Encumbrance

    Data.gov (United States)

    US Forest Service, Department of Agriculture — A map service designed to portray US Forest Service Land Status Record System data. The map service is for querying and displaying Land Status Record System...

  4. Status of TRANSP/PTRANSP

    Science.gov (United States)

    McCune, Douglas; Andre, Rob; Feibush, Eliot; Gorelenkova, Marina; Ludescher-Furth, Christiane; Yuan, Xingqiu

    2011-10-01

    This poster summarizes the status of TRANSP/PTRANSP code development and run production operations. Production system utilization rates, particularly for MPI jobs, continue to climb. The poster will show production system utilization history and describe status and plans for production facilities and supporting software, as well as the major areas of physics code development. The major physics areas are: simulation using free boundary MHD equilibrium (ISOLVER); neutral beam and fusion product fast ion heating and current drive (NUBEAM); RF heating and current drive (TORIC, GENRAY, and other codes); and predictive transport modeling (PTRANSP and associated modular solvers). In addition, there have been promising advances in capabilities for post-processing and analysis of TRANSP results, based on the SWIM Plasma State software; these too will be described.

  5. Drug-induced status epilepticus.

    Science.gov (United States)

    Cock, Hannah R

    2015-08-01

    Drug-induced status epilepticus (SE) is a relatively uncommon phenomenon, probably accounting for less than 5% of all SE cases, although limitations in case ascertainment and establishing causation substantially weaken epidemiological estimates. Some antiepileptic drugs, particularly those with sodium channel or GABA(γ-aminobutyric acid)-ergic properties, frequently exacerbate seizures and may lead to SE if used inadvertently in generalized epilepsies or less frequently in other epilepsies. Tiagabine seems to have a particular propensity for triggering nonconvulsive SE sometimes in patients with no prior history of seizures. In therapeutic practice, SE is most commonly seen in association with antibiotics (cephalosporins, quinolones, and some others) and immunotherapies/chemotherapies, the latter often in the context of a reversible encephalopathy syndrome. Status epilepticus following accidental or intentional overdoses, particularly of antidepressants or other psychotropic medications, has also featured prominently in the literature: whilst there are sometimes fatal consequences, this is more commonly because of cardiorespiratory or metabolic complications than as a result of seizure activity. A high index of suspicion is required in identifying those at risk and in recognizing potential clues from the presentation, but even with a careful analysis of patient and drug factors, establishing causation can be difficult. In addition to eliminating the potential trigger, management should be as for SE in any other circumstances, with the exception that phenobarbitone is recommended as a second-line treatment for suspected toxicity-related SE where the risk of cardiovascular complications is higher anyways and may be exacerbated by phenytoin. There are also specific recommendations/antidotes in some situations. The outcome of drug-induced status epilepticus is mostly good when promptly identified and treated, though less so in the context of overdoses. This article is

  6. Happiness and Sexual Minority Status.

    Science.gov (United States)

    Thomeer, Mieke Beth; Reczek, Corinne

    2016-10-01

    We used logistic regression on nationally representative data (General Social Survey, N = 10,668 and N = 6680) to examine how sexual minority status related to happiness. We considered two central dimensions of sexual minority status-sexual behavior and sexual identity. We distinguished between same-sex, both-sex, and different-sex-oriented participants. Because individuals transition between sexual behavior categories over the life course (e.g., from both-sex partners to only same-sex partners) and changes in sexual minority status have theoretical associations with well-being, we also tested the associations of transitions with happiness. Results showed that identifying as bisexual, gay, or lesbian, having both male and female partners since age 18, or transitioning to only different-sex partners was negatively related to happiness. Those with only same-sex partners since age 18 or in the past 5 years had similar levels of happiness as those with only different-sex partners since age 18. Additional tests showed that the majority of these happiness differences became non-significant when economic and social resources were included, indicating that the lower happiness was a product of structural and societal forces. Our findings clearly and robustly underscored the importance of taking a multi-faceted approach to understanding sexuality and well-being, demonstrating that not all sexual minority groups experience disadvantaged happiness. Our study calls for more attention to positive aspects of well-being such as happiness in examinations of sexual minorities and suggests that positive psychology and other happiness subfields should consider the role of sexual minority status in shaping happiness.

  7. Atmospheric neutrinos: Status and prospects

    OpenAIRE

    2016-01-01

    We present an overview of the current status of neutrino oscillation studies at atmospheric neutrino experiments. While the current data gives some tentalising hints regarding the neutrino mass hierarchy, octant of $\\theta_{23}$ and $\\delta_{CP}$, the hints are not statistically significant. We summarise the sensitivity to these sub-dominant three-generation effects from the next-generation proposed atmospheric neutrino experiments. We next present the prospects of new physics searches such a...

  8. Status of the VERITAS Observatory

    CERN Document Server

    Holder, J; Aliu, E; Arlen, T; Beilicke, M; Benbow, W; Bradbury, S M; Buckley, J H; Bugaev, V; Butt, Y; Byrum, K L; Cannon, A; Celik, O; Cesarini, A; Ciupik, L; Chow, Y C K; Cogan, P; Colin, P; Cui, W; Daniel, M K; Ergin, T; Falcone, A D; Fegan, S J; Finley, J P; Finnegan, G; Fortin, P; Fortson, L F; Furniss, A; Gillanders, G H; Grube, J; Guenette, R; Gyuk, G; Hanna, D; Hays, E; Horan, D; Hui, C M; Humensky, T B; Imran, A; Kaaret, Philip; Karlsson, N; Kertzman, M; Kieda, D B; Kildea, J; Konopelko, A; Krawczynski, H; Krennrich, F; Lang, M J; Le Bohec, S; Maier, G; McCann, A; McCutcheon, M; Moriarty, P; Mukherjee, R; Nagai, T; Niemiec, J; Ong, R A; Pandel, D; Perkins, J S; Pohl, M; Quinn, J; Ragan, K; Reyes, L C; Reynolds, P T; Rose, H J; Schroedter, M; Sembroski, G H; Smith, A W; Steele, D; Swordy, S P; Toner, J A; Valcarcel, L; Vasilev, V V; Wagner, R; Wakely, S P; Ward, J E; Weekes, T C; Weinstein, A; White, R J; Williams, D A; Wissel, S A; Wood, M; Zitzer, B

    2008-01-01

    VERITAS, an Imaging Atmospheric Cherenkov Telescope (IACT) system for gammma-ray astronomy in the GeV-TeV range, has recently completed its first season of observations with a full array of four telescopes. A number of astrophysical gamma-ray sources have been detected, both galactic and extragalactic, including sources previously unknown at TeV energies. We describe the status of the array and some highlight results, and assess the technical performance, sensitivity and shower reconstruction capabilities.

  9. The TEMPIS Project: Current Status,

    Science.gov (United States)

    1987-06-19

    GRA&I 9 [ Valiente 19871 jC A 10 [Aba 1986AJ tnannounced ŕ [Ahn~ 1986B] oation- Table 1: Status of Subtasks Distribut on/ ____ Avail and/or 3 WkM On...W ~~ -tt-,u Rr ~~ n~ m1 Nn VJs -W r a -VW uS ru-p-urp-Vf U, 8 39. [ Valiente 19871 Valiente , J. Implementing TQuel Aggregates (in progress). Master’s

  10. Social Status Identity: Antecedents and Vocational Outcomes

    Science.gov (United States)

    Thompson, Mindi N.; Subich, Linda M.

    2011-01-01

    This study extended the literature on potential antecedents and outcomes of perceived social status, or differential status identity (DSI). Fouad and Brown's DSI was used as a conceptual lens for examining the relation of supports and barriers to an individual's perceived social status and subsequent career indecisiveness and career decision…

  11. 27 CFR 28.30 - Export status.

    Science.gov (United States)

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Export status. 28.30... Export status. (a) Distilled spirits and wines manufactured, produced, bottled in bottles packed in... such purposes are considered to be exported. Export status is not acquired until application on...

  12. Management of Status Epilepticus in Children

    Directory of Open Access Journals (Sweden)

    Douglas M. Smith

    2016-04-01

    Full Text Available Status epilepticus is a common pediatric neurological emergency. Management includes prompt administration of appropriately selected anti-seizure medications, identification and treatment of seizure precipitant(s, as well as identification and management of associated systemic complications. This review discusses the definitions, classification, epidemiology and management of status epilepticus and refractory status epilepticus in children.

  13. Renewables 2013. Global Status Report

    Energy Technology Data Exchange (ETDEWEB)

    Sawin, J.L. (ed.) [and others

    2013-07-01

    Renewable energy markets, industries, and policy frameworks have evolved rapidly in recent years. The Renewables Global Status Report provides a comprehensive and timely overview of renewable energy market, industry, investment, and policy developments worldwide. It relies on the most recent data available, provided by many contributors and researchers from around the world, all of which is brought together by a multi-disciplinary authoring team. The report covers recent developments, current status, and key trends; by design, it does not provide analysis or forecasts. This latest Renewables Global Status Report saw: a shift in investment patterns that led to a global decrease in clean energy investment; continuing growth in installed capacity due to significant technology cost reductions and increased investment in developing countries; renewables progressively supplementing established electricity systems, demonstrating that the implementation of suitable policies can enable the successful integration of higher shares of variable renewables; and the emergence of integrated policy approaches that link energy efficiency measures with the implementation of renewable energy technologies.

  14. Socio-Economic Status and Occupational Status Projections of Southern Youth, By Race and Sex.

    Science.gov (United States)

    Lever, Michael F.; Kuvlesky, William P.

    The purpose of this study was to examine selected occupational status projections and the relationship between these projections and socioeconomic status (SES). Occupational status projections referred to predictive statements about the future lifetime job of the respondents. The occupational status projections included in the analysis were: (1)…

  15. Preference for High Status Predicts Implicit Outgroup Bias among Children from Low-Status Groups

    Science.gov (United States)

    Newheiser, Anna-Kaisa; Dunham, Yarrow; Merrill, Anna; Hoosain, Leah; Olson, Kristina R.

    2014-01-01

    Whereas members of high-status racial groups show ingroup preference when attitudes are measured implicitly, members of low-status racial groups--both adults and children--typically show no bias, potentially reflecting awareness of the ingroup's low status. We hypothesized that when status differences are especially pronounced, children from…

  16. Reducing status quo bias in choice experiments

    DEFF Research Database (Denmark)

    Bonnichsen, Ole; Ladenburg, Jacob

    In stated preference literature, the tendency to choose the alternative representing the status quo situation seems to exceed real life status quo effects. Accordingly, status quo bias can be a problem. In Choice Experiments, status quo bias is found to be strongly correlated with protest attitudes...... toward the cost attribute. If economic values are to be elicited, this problem is difficult to remedy. In a split sample framework we test a novel ex-ante entreaty aimed specifically at the cost attribute and find that it effectively reduces status quo bias and improves the internal validity...

  17. The Retinal Readout System: a status report A Status Report

    CERN Document Server

    Litke, A M

    1999-01-01

    The 'Retinal Readout System' is being developed to study the language the eye uses to send information about the visual world to the brain. Its architecture is based on that of silicon microstrip detectors. An array of 512 microscopic electrodes picks up the signals generated by the output neurons of live retinal tissue in response to a dynamic image focused on the input neurons. These signals are amplified, filtered and multiplexed by a set of eight custom-designed VLSI readout chips, and digitized and recorded by a data acquisition system. This report describes the goals, design, and status of the system. (author)

  18. State building energy codes status

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1996-09-01

    This document contains the State Building Energy Codes Status prepared by Pacific Northwest National Laboratory for the U.S. Department of Energy under Contract DE-AC06-76RL01830 and dated September 1996. The U.S. Department of Energy`s Office of Codes and Standards has developed this document to provide an information resource for individuals interested in energy efficiency of buildings and the relevant building energy codes in each state and U.S. territory. This is considered to be an evolving document and will be updated twice a year. In addition, special state updates will be issued as warranted.

  19. Mobile satellite plans and status

    Science.gov (United States)

    Anderson, Roy E.

    1987-03-01

    A method for implementing a mobile satellite system (MSS) in the U.S. and Canada, and the services such a system would provide are described. The MSS is to provide mobile communications that are unlimited in range and unaffected by local terrain features. The system's communications can be either voice or digital, and the small, automatic transponders located in vehicles will respond automatically with the data needed to determine the location of the vehicle. Surveys reveal that there are markets for radio telephones and data and dispatch services. Consideration is given to the regulatory status of the MSS.

  20. Status of LLNL granite projects

    Energy Technology Data Exchange (ETDEWEB)

    Ramspott, L.D.

    1980-12-31

    The status of LLNL Projects dealing with nuclear waste disposal in granitic rocks is reviewed. This review covers work done subsequent to the June 1979 Workshop on Thermomechanical Modeling for a Hardrock Waste Repository and is prepared for the July 1980 Workshop on Thermomechanical-Hydrochemical Modeling for a Hardrock Waste Repository. Topics reviewed include laboratory determination of thermal, mechanical, and transport properties of rocks at conditions simulating a deep geologic repository, and field testing at the Climax granitic stock at the USDOE Nevada Test Site.

  1. Renewables 2005. Global status report

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2005-07-01

    This report provides an overview of the status of renewable energy worldwide in 2005. It covers markets, investments, industries, policies, and rural (off-grid) renewable energy in developing countries. By design, the report does not provide analysis, recommendations, or conclusions. An extensive research and review process over several months involving more than 100 researchers and contributors has kept inaccuracies to a minimum. REN21 sees this report as the beginning of an active exchange of views and information. This report reveals some surprising facts about renewable energy, many reflecting strong growth trends and increasing significance relative to conventional energy. (au)

  2. LHC Status and Upgrade Challenges

    Science.gov (United States)

    Smith, Jeffrey

    2009-11-01

    The Large Hadron Collider has had a trying start-up and a challenging operational future lays ahead. Critical to the machine's performance is controlling a beam of particles whose stored energy is equivalent to 80 kg of TNT. Unavoidable beam losses result in energy deposition throughout the machine and without adequate protection this power would result in quenching of the superconducting magnets. A brief overview of the machine layout and principles of operation will be reviewed including a summary of the September 2008 accident. The current status of the LHC, startup schedule and upgrade options to achieve the target luminosity will be presented.

  3. SEEDS Moving Group Status Update

    Science.gov (United States)

    McElwain, Michael

    2011-01-01

    I will summarize the current status of the SEEDS Moving Group category and describe the importance of this sub-sample for the entire SEEDS survey. This presentation will include analysis of the sensitivity for the Moving Groups with general a comparison to other the other sub-categories. I will discuss the future impact of the Subaru SCExAO system for these targets and the advantage of using a specialized integral field spectrograph. Finally, I will present the impact of a pupil grid mask in order to produce fiducial spots in the focal plane that can be used for both photometry and astrometry.

  4. Atmospheric Neutrinos: Status and Prospects

    CERN Document Server

    Choubey, Sandhya

    2016-01-01

    We present an overview of the current status of neutrino oscillation studies at atmospheric neutrino experiments. While the current data gives some tentalising hints regarding the neutrino mass hierarchy, octant of $\\theta_{23}$ and $\\delta_{CP}$, the hints are not statistically significant. We summarise the sensitivity to these sub-dominant three-generation effects from the next-generation proposed atmospheric neutrino experiments. We next present the prospects of new physics searches such as non-standard interactions, sterile neutrinos and CPT violation studies at these experiments.

  5. Atmospheric neutrinos: Status and prospects

    Science.gov (United States)

    Choubey, Sandhya

    2016-07-01

    We present an overview of the current status of neutrino oscillation studies at atmospheric neutrino experiments. While the current data gives some tantalising hints regarding the neutrino mass hierarchy, octant of θ23 and δCP, the hints are not statistically significant. We summarise the sensitivity to these sub-dominant three-generation effects from the next-generation proposed atmospheric neutrino experiments. We next present the prospects of new physics searches such as non-standard interactions, sterile neutrinos and CPT violation studies at these experiments.

  6. Socioeconomic status and fertility decline

    DEFF Research Database (Denmark)

    Dribe, Martin; Breschi, Marco; Gagnon, Alain

    2017-01-01

    America to analyse the relationship between socio-economic status and fertility during the fertility transition. Using comparable analytical models and class schemes for each population, we examined the changing socio-economic differences in marital fertility and related these to common theories...... on fertility behaviour. Our results do not provide support for the hypothesis of universally high fertility among the upper classes in pre-transitional society, but do support the idea that the upper classes acted as forerunners by reducing their fertility before other groups. Farmers and unskilled workers...

  7. Renewables 2012. Global Status Report

    Energy Technology Data Exchange (ETDEWEB)

    Sawin, J.L. (ed.) [and others

    2012-08-15

    Renewable energy markets and policy frameworks have evolved rapidly in recent years. This report provides a comprehensive and timely overview of renewable energy market, industry, investment, and policy developments worldwide. It relies on the most recent data available, provided by a network of more than 400 contributors and researchers from around the world, all of which is brought together by a multi-disciplinary authoring team. The report covers recent developments, current status, and key trends; by design, it does not provide analysis or forecast the future.

  8. Top Quark Current Experimental Status

    CERN Document Server

    Juste, A

    2006-01-01

    Ten years after its discovery at the Tevatron collider, we still know little about the top quark. Its large mass suggests it may play a key role in the mechanism of Electroweak Symmetry Breaking (EWSB), or open a window of sensitivity to new physics related to EWSB and preferentially coupled to it. To determine whether this is the case, precision measurements of top quark properties are necessary. The high statistics samples being collected by the Tevatron experiments during Run II start to incisively probe the top quark sector. This report summarizes the experimental status of the top quark, focusing in particular on the recent measurements from the Tevatron.

  9. Probe Project Status and Accomplishments

    Energy Technology Data Exchange (ETDEWEB)

    Burris, RD

    2001-05-07

    The Probe project has completed its first full year of operation. In this document we will describe the status of the project as of December 31, 2000. We will describe the equipment configuration, then give brief descriptions of the various projects undertaken to date. We will mention first those projects performed for outside entities and then those performed for the benefit of one of the Probe sites. We will then describe projects that are under consideration, including some for which initial actions have been taken and others which are somewhat longer-term.

  10. Status epilepticus and cluster seizures.

    Science.gov (United States)

    Patterson, Edward Ned E

    2014-11-01

    Status epilepticus (SE) is a medical emergency for companion animals, with significant associated morbidity and mortality. Therapy in companion animals and people has been largely with sedatives and anesthetics, many of which have gamma-aminobutyric acid receptor-mediated mechanisms. Early aggressive treatment includes staged first-line therapy with benzodiazepines, and second- and third-line protocols when needed. Recently, intravenous levetiracetam has also been used in for SE in dogs and people, and there are other human intravenous drug preparations that may hold promise for future use in companion animals.

  11. Status of RDMS CMS computing

    Science.gov (United States)

    Gavrilov, V.; Golutvin, I.; Kodolova, O.; Korenkov, V.; Levchuk, L.; Shmatov, S.; Tikhonenko, E.; Zhiltsov, V.

    2016-09-01

    The Compact Muon Solenoid (CMS) is a high-performance general-purpose detector at the Large Hadron Collider (LHC) at CERN. More than twenty institutes from Russia and Joint Institute for Nuclear Research (JINR) are involved in Russia and Dubna Member States (RDMS) CMS Collaboration. A proper computing grid-infrastructure has been constructed at the RDMS institutes for the participation in the running phase of the CMS experiment. Current status of RDMS CMS computing and plans of its development to the next LHC start are presented.

  12. Status of the GRANIT facility

    CERN Document Server

    Roulier, Damien; Baessler, Stefan; Clément, Benoît; Morton, Daniel; Nesvizhevsky, Valery; Pignol, Guillaume; Rebreyend, Dominique

    2014-01-01

    The GRANIT facility is a follow-up project, which is motivated by the recent discovery of gravitational quantum states of ultracold neutrons. The goal of the project is to approach the ultimate accuracy in measuring parameters of such quantum states and also to apply this phenomenon and related experimental techniques to a broad range of applications in particle physics as well as in surface and nanoscience studies. We overview the current status of this facility, the recent test measurements and the nearest prospects.

  13. Periodontal Status of Postmenopausal Women

    Directory of Open Access Journals (Sweden)

    Timur V. Melkumyan

    2014-06-01

    Full Text Available The objective of this study was to compare the periodontal status in postmenopausal women with osteopenia and osteoporosis. Material and Methods: We examined 43 postmenopausal women aged from 55 to 74 years. Material assessment of bones in every patient was performed by means of dual energy X-ray absorptiometry (DXA from two points on the skeleton – part of the femur neck and between the first and fourth lumbar vertebrae. A lipid blood test was done for patients of both groups. All patients were divided into two groups (the 1st with osteopenia, and the 2nd with osteoporosis. All patients were subjected to an oral clinical examination: the periodontal examination was composed of Plaque Index (PI, Pocket Score (PS, and Papillary Bleeding Index (PBI. X-ray analysis was performed for every patient. Results: The results of the clinical periodontal examination demonstrated that the mean PBI in patients in the 1st group had no significant differences from the PBI in patients in the 2nd group. PI value and PS findings in patients with general osteoporosis also had no statistical differences from the same parameters in patients with osteopenia. Conclusion: Under the circumstances of these patients’ characteristics and within the limits of the present study, we concluded that there is no significant difference in the periodontal status of postmenopausal women with systemic osteopenia and with osteoporosis.

  14. Occlusal status among Yemeni children

    Directory of Open Access Journals (Sweden)

    Nabil M Al-Zubair

    2014-01-01

    Full Text Available Objectives: The purpose of this study was to assess the occlusal status in schoolchildren in Yemen, and to compare the results with those of other studies. Materials and Methods: The sample for this epidemiological survey consisted of 3003 primary school students, half of whom were boys and the other half girls, aged 12 years. The subjects were randomly selected, and none had received previous orthodontic treatment. Variables examined included intra-arch irregularities and malalignment (crowding and spacing in the incisal segments of the arch and midline diastema and discrepancies in occlusal contact relationship (maxillary overjet, mandibular overjet, anterior openbite and antero-posterior molar relation. Results: The results showed that about 26.1% of the subjects were still in the late mixed dentition stage and 73.9% presented with a dentition in the early permanent stage. Normal overjet was found in 55% of the sample. Crowding was observed in 31.4% of the subjects and midline diastema in 14.2%. Conclusion: Occlusal status among Yemeni children was characterized by a relatively high frequency of dental crowding, as well as a relatively high frequency of anterior mandibular overjet (Class III malocclusions.

  15. Status of the CBM experiment

    Directory of Open Access Journals (Sweden)

    Heuser Johann M.

    2015-01-01

    Full Text Available The Compressed Baryonic Matter (CBM experiment at the Facility for Anti-Proton and Ion Research (FAIR will explore the phase diagram of strongly interacting matter at highest net baryon densities and moderate temperatures. The CBM physics program will be started with beams delivered by the SIS 100 synchrotron, providing energies from 2 to 11 GeV/nucleon for heavy nuclei, up to 14 GeV/nucleon for light nuclei, and 29 GeV for protons. The highest net baryon densities will be explored with ion beams up to 45 GeV/nucleon energy delivered by SIS 300 in the next stage of FAIR. Collision rates up to 107 per second are required to produce very rare probes with unprecedented statistics in this energy range. Their signatures are complex. These conditions call for detector systems designed to meet the extreme requirements in terms of rate capability, momentum and spatial resolution, and a novel DAQ and trigger concept which is not limited by latency but by throughput. The article discusses the development status of the CBM sub-systems for charged particle tracking, vertex detection, electron/muon identification, hadron/time-of-flight measurement, electromagnetic and zero-degree calorimetry, in terms of prototypes and expected physics performance. The concept and development status of CBM’s central detector, the Silicon Tracking System STS are presented in somewhat more detail.

  16. Repository development status in Spain

    Energy Technology Data Exchange (ETDEWEB)

    Rodriguez Beceiro, Alvaro; Zuloaga, Pablo [ENRESA (Spain)

    2009-06-15

    The paper describes the status of repository development for the different waste categories. Low and Intermediate Waste Disposal facility of El Cabril was commissioned in 1992 and is in normal operation. The major modifications and activities during the last years are the adaptation to waste streams not initially foreseen such as some decommissioning waste or waste from steel industry, and the improvement of its performance assessment, supported by a R and D and refined models. As part of this facility, a new disposal facility specifically intended for very low activity waste has been constructed and commissioned in July 2008. Its design is based on the European Directive for hazardous waste disposal. National policy for Nuclear Spent Fuel and High-Level waste is focused on the development of a centralized storage facility of the vault type, whose site location would be selected through a volunteering process. Meanwhile, with the aim of solving specific problems, three individual storage facilities are in different status at reactor sites. Research on final solution, including some repository aspects as well as separation and transmutation are being carried out in accordance to ENRESA's R and D program. ENRESA has developed conceptual designs for non site specific repositories, both in granite and clay, and has carried out their corresponding performance assessment exercises. (authors)

  17. Stiripentol in refractory status epilepticus.

    Science.gov (United States)

    Grosenbaugh, Denise K; Mott, David D

    2013-09-01

    Benzodiazepines (BZDs), which enhance γ-aminobutyric acid (GABAA ) receptor-mediated inhibition, are the first-line therapy for treatment of status epilepticus (SE). However, pharmacoresistance to BZDs develops rapidly after SE initiation. This is due to an activity-dependent internalization of BZD-sensitive GABAA receptors during SE. Stiripentol (STP) is a positive allosteric modulator of GABAA receptors with a unique subunit selectivity profile. We report that in a rodent model of SE, STP terminates behavioral seizures and remains effective in established SE when seizures have become BZD resistant. The anticonvulsant effects of STP are age dependent, with greater potency in juvenile animals. Whole cell recordings from dentate granule cells in hippocampal slices reveal that STP potentiates GABAergic inhibitory postsynaptic currents (IPSCs) and tonic GABAergic currents by acting at a site on the GABAA receptor that is separate from the benzodiazepine binding site. This potentiation persists in established SE, whereas potentiation of GABAergic inhibition by BZDs is lost. STP potentiates IPSCs in juvenile animals with greater potency than in adult animals. We suggest that STP, either alone or as add-on therapy, may prove useful in treating established and BZD-resistant status epilepticus. Furthermore, STP may be particularly effective in terminating SE in children when SE is most prevalent.

  18. Status of the CBM experiment

    Science.gov (United States)

    Heuser, Johann M.

    2015-05-01

    The Compressed Baryonic Matter (CBM) experiment at the Facility for Anti-Proton and Ion Research (FAIR) will explore the phase diagram of strongly interacting matter at highest net baryon densities and moderate temperatures. The CBM physics program will be started with beams delivered by the SIS 100 synchrotron, providing energies from 2 to 11 GeV/nucleon for heavy nuclei, up to 14 GeV/nucleon for light nuclei, and 29 GeV for protons. The highest net baryon densities will be explored with ion beams up to 45 GeV/nucleon energy delivered by SIS 300 in the next stage of FAIR. Collision rates up to 107 per second are required to produce very rare probes with unprecedented statistics in this energy range. Their signatures are complex. These conditions call for detector systems designed to meet the extreme requirements in terms of rate capability, momentum and spatial resolution, and a novel DAQ and trigger concept which is not limited by latency but by throughput. The article discusses the development status of the CBM sub-systems for charged particle tracking, vertex detection, electron/muon identification, hadron/time-of-flight measurement, electromagnetic and zero-degree calorimetry, in terms of prototypes and expected physics performance. The concept and development status of CBM's central detector, the Silicon Tracking System STS are presented in somewhat more detail.

  19. Sensors for observing ecosystem status

    Directory of Open Access Journals (Sweden)

    S. Kröger

    2009-04-01

    Full Text Available This paper aims to review the availability and application of sensors for observing marine ecosystem status. It gives a broad overview of important ecosystem variables to be investigated, such as biogeochemical cycles, primary and secondary production, species distribution, animal movements, habitats and pollutants. Some relevant legislative drivers are listed, as they provide one context in which ecosystem studies are undertaken. In addition to literature cited within the text the paper contains some useful web links to assist the reader in making an informed instrument choice, as the authors feel that the topic is so broad, it is impossible to discuss all relevant systems or to provide appropriate detail for those discussed. This is therefore an introduction to how and why ecosystem status is currently observed, what variables are quantified, from what platforms, using remote sensing or in-situ measurements, and gives examples of useful sensor based tools. Starting with those presently available, to those under development and also highlighting sensors not yet realised but desirable for future studies.

  20. Sensors for observing ecosystem status

    Directory of Open Access Journals (Sweden)

    S. Kröger

    2009-11-01

    Full Text Available This paper aims to review the availability and application of sensors for observing marine ecosystem status. It gives a broad overview of important ecosystem variables to be investigated, such as biogeochemical cycles, primary and secondary production, species distribution, animal movements, habitats and pollutants. Some relevant legislative drivers are listed, as they provide one context in which ecosystem studies are undertaken. In addition to literature cited within the text the paper contains some useful web links to assist the reader in making an informed instrument choice, as the authors feel that the topic is so broad, it is impossible to discuss all relevant systems or to provide appropriate detail for those discussed. It is therefore an introduction to how and why ecosystem status is currently observed, what variables are quantified, from what platforms, using remote sensing or in-situ measurements, and gives examples of useful sensor based tools. Starting with those presently available, to those under development and also highlighting sensors not yet realised but desirable for future studies.

  1. Status Report on SPARC Project

    CERN Document Server

    Renieri, Alberto; Ciocci, Franco; Dattoli, Giuseppe; Di Pace, Antonio; Doria, Andrea; Flora, Francesco; Gallerano, G P; Giannessi, Luca; Giovenale, Emilio; Messina, Giovanni; Mezi, Luca; Ottaviani, P L; Pagnutti, Simonetta; Parisi, Giovanni; Picardi, Luigi; Quattromini, Marcello; Ronci, Giuseppe; Ronsivalle, Concetta; Sabia, Elio; Sassi, Mauro; Zucchini, Alberto

    2004-01-01

    We review the status of FEL source activity of the on going SPARC FEL experiment, developed within the framework of a collaboration among ENEA, CNR, INFN, INFM, Sincrotrone Trieste and University of Rome Tor Vergata. The project is aimed at realising a SASE FEL source, operating in the visible (around 500 nm), with an extended range of tunability down to the VUV (100nm) by the use of the mechanism of non-linear harmonic generation. The development of the relevant activities foresees the realisation of an advanced 150 MeV photo-injector source, aimed at producing a high brightness electron beams, needed to drive a SASE-FEL experiment and a 12 m long undulator. We present the status of the design and construction of the injector, of the undulator and of the e-beam transport line. In particular we discuss the choice of the project parameters, their optimisation and the sensitivity of the SPARC performance to any parameter variation. We will show, using start to-end simulations, what is the impact of the e-beam a...

  2. MENA Renewables Status Report 2013

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2013-06-15

    The MENA Renewables Status Report is an outcome of ADIREC, the Abu Dhabi International Renewable Energy Conference. The report provides a status overview of renewable energy markets, industry, policy and investment trends in the region, drawing on the most recent data available. It is produced in cooperation with over 50 contributors and researchers in the region and reveals massive growth in the renewable energy markets of the Middle East and North Africa (MENA). Regional investment topped US$2.9 billion in 2012, up 40% from 2011 and 650% from 2004. With over 100 projects under development, the region could see a 450% increase in non-hydro renewable energy generating capacity in the next few years. For the report, the 21 MENA countries were clustered into two sub-groups: Net Oil-Exporting Countries (NOEC) -- Algeria, Bahrain, Egypt, Iran, Iraq, Kuwait, Libya, Oman, Qatar, Saudi Arabia, Syria, United Arab Emirates, and Yemen; and Net Oil-Importing Countries (NOIC) -- Djibouti, Israel, Jordan, Lebanon, Malta, Morocco, Palestine, and Tunisia.

  3. Status of current IPH applications

    Energy Technology Data Exchange (ETDEWEB)

    Kearney, D. W.

    1981-03-01

    The US Department of Energy has funded a series of field tests since 1977 to gain operational experience in the application of solar energy to industrial process heat requirements. To date, 34 design studies or actual installations have been funded utilizing technologies ranging from flat plates to line-focus concentrators to central receiver industrial systems. The types of solar systems include hot air, hot water, and steam production applied to a broad spectrum of industrial processes. The program elements are identified and put in perspective relative to transport fluid, temperature level, and size of the solar field. The status of these programs ranges from design studies to operational systems. Solar enhanced oil recovery and repowering have been studied. The chronological history of each program is tabulated. (LEW)

  4. Status of the Majorana Demonstrator

    Energy Technology Data Exchange (ETDEWEB)

    Cuesta, C.; Abgrall, N.; Arnquist, Isaac J.; Avignone, Frank T.; Barabash, Alexander S.; Bertrand, F.; Brudanin, V.; Busch, Matthew; Buuck, M.; Byram, D.; Caldwell, A. S.; Chan, Yuen-Dat; Christofferson, Cabot-Ann; Detwiler, Jason A.; Efremenko, Yuri; Ejiri, H.; Elliott, S. R.; Galindo-Uribarri, A.; Giovanetti, G. K.; Goett, J.; Green, M. P.; Gruszko, J.; Guinn, I.; Guiseppe, V. E.; Henning, R.; Hoppe, Eric W.; Howard, Stanley; Howe, M. A.; Jasinski, B. R.; Keeter, K.; Kidd, M. F.; Konovalov, S.; Kouzes, Richard T.; Laferriere, Brian D.; Leon, Jonathan D.; MacMullin, J.; Martin, R. D.; Meijer, S. J.; Mertens, S.; Orrell, John L.; O' Shaughnessy, C.; Overman, Nicole R.; Poon, Alan; Radford, D. C.; Rager, J.; Rielage, Keith; Robertson, R. G. H.; Romero-Romero, E.; Schmitt, C.; Shanks, B.; Shirchenko, M.; Snyder, N.; Suriano, Anne-Marie; Tedeschi, D.; Timkin, V.; Trimble, J. E.; Varner, R. L.; Vasilyev, Sergey; Vetter, Kai; Vorren, Kris R.; White, Brandon R.; Wilkerson, J. F.; Wiseman, C.; Xu, W.; Yakushev, E.; Yu, Chang-Hong; Yumatov, Vladimir

    2015-06-09

    The Majorana Collaboration is constructing the Majorana Demonstrator, an ultra-low background, 40-kg modular high purity Ge detector array to search for neutrinoless double-beta decay in 76Ge. In view of the next generation of tonne-scale Ge-based neutrinoless double-beta decay searches that will probe the neutrino mass scale in the inverted hierarchy region, a major goal of the Demonstrator is to demonstrate a path forward to achieving a background rate at or below 1 count/tonne/year in the 4 keV region of interest around the Q-value at 2039 keV. The current status of the Demonstrator is discussed, as are plans for its completion.

  5. FRIB Front End Design Status

    CERN Document Server

    Pozdeyev, E; Machicoane, G; Morgan, G; Rao, X; Zhao, Q; Stovall, J; Vorozhtsov, S; Sun, L

    2013-01-01

    The Facility for Rare Isotope Beams (FRIB) will provide a wide range of primary ion beams for nuclear physics research with rare isotope beams. The FRIB SRF linac will be capable of accelerating medium and heavy ion beams to energies beyond 200 MeV/u with a power of 400 kW on the fragmentation target. This paper presents the status of the FRIB Front End designed to produce uranium and other medium and heavy mass ion beams at world-record intensities. The paper describes the FRIB high performance superconducting ECR ion source, the beam transport designed to transport two-charge state ion beams and prepare them for the injection in to the SRF linac, and the design of a 4-vane 80.5 MHz RFQ. The paper also describes the integration of the front end with other accelerator and experimental systems.

  6. Status of the MAJORANA Demonstrator

    CERN Document Server

    Cuesta, C; Arnquist, I J; Avignone, F T; Barabash, A S; Bertrand, F E; Brudanin, V; Busch, M; Buuck, M; Byram, D; Caldwell, A S; Chan, Y-D; Christofferson, C D; Detwiler, J A; Efremenko, Yu; Ejiri, H; Elliott, S R; Galindo-Uribarri, A; Giovanetti, G K; Goett, J; Greenn, M P; Gruszko, J; Guinn, I S; Guiseppe, V E; Henning, R; Hoppe, E W; Howard, S; Howe, M A; Jasinski, B R; Keeter, K J; Kidd, M F; Konovalov, S I; Kouzes, R T; LaFerriere, B D; Leon, J; MacMullin, J; Martin, R D; Meijer, S J; Mertens, S; Orrell, J L; O'Shaughnessy, C; Overman, N R; Poon, A W P; Radford, D C; Rager, J; Rielage, K; Robertson, R G H; Romero-Romero, E; Schmitt, C; Shanks, B; Shirchenko, M; Snyder, N; Suriano, A M; Tedeschi, D; Timkin, V; Trimble, J E; Varner, R L; Vasilyev, S; Vetter, K; Vorren, K; White, B R; Wilkerson, J F; Wiseman, C; Xu, W; Yakushev, E; Yu, C -H; Yumatov, V

    2014-01-01

    The MAJORANA Collaboration is constructing the MAJORANA Demonstrator, an ultra-low background, 40-kg modular high purity Ge detector array to search for neutrinoless double-beta decay in Ge. In view of the next generation of tonne-scale Ge-based neutrinoless double-beta decay searches that will probe the neutrino mass scale in the inverted-hierarchy region, a major goal of the Demonstrator is to demonstrate a path forward to achieving a background rate at or below 1 count/tonne/year in the 4 keV region of interest around the Q-value at 2039 keV. The current status of the Demonstrator is discussed, as are plans for its completion.

  7. Status of the KATRIN experiment

    Energy Technology Data Exchange (ETDEWEB)

    Roellig, Marco [Karlsruher Institut fuer Technologie (KIT) (Germany); Collaboration: KATRIN-Collaboration

    2016-07-01

    A model-independent measurement of the neutrino mass is one of the most important open issues in neutrino physics. The KArlsruhe Tritium Neutrino Experiment (KATRIN) aims for it with an unprecedented sensitivity of m {sub anti} {sub ν{sub e}} < 200 meV (90% C.L.). While the commissioning of the high resolution MAC-E Filter and the main detector is ongoing also all tritium related components have arrived at KIT. At the Tritium Laboratory Karlsruhe the on-site finalization and commisioning of the tritium related parts has started. A status report on all source and transport components of KATRIN as well as the spectrometer and detector section is given. Also the integration into the existing tritium infrastructure is described.

  8. ESA's SMART-1 Mission: Status

    Science.gov (United States)

    Racca, G.; Foing, B. H.; SMART-1 Project Team

    SMART-1 is the first of Small Missions for Advanced Research and Technology as part of ESA science programme ``Cosmic Vision''. Its objective is to demonstrate Solar Electric Primary Propulsion (SEP) for future Cornerstones (such as Bepi-Colombo) and to test new technologies for spacecraft and instruments. The spacecraft has been launched on 27 sept. 2003, as an Ariane-5 auxiliary passenger. SMART-1 orbit pericenter is now outside the inner radiation belt. The current status of SMART-1 will be given at the symposium. After a 15 month cruise with primary SEP, the SMART-1 mission is to orbit the Moon for a nominal period of six months, with possible extension. The spacecraft will carry out a complete programme of scientific observations during the cruise and in lunar orbit.

  9. Construction Status of Linac4

    CERN Document Server

    Gerigk, F; Garoby, R; Hanke, K; Lombardi, A M; MacCaferri, R; Maury, S; Rossi, C; Vretenar, M

    2010-01-01

    The civil engineering works of the Linac4 linear accelerator at CERN started in October 2008 and regular machine operation is foreseen for 2013. Linac4 will accelerate H−ions to an energy of 160 MeV for injection into the PS Booster (PSB). It will thus replace the ageing Linac2, which presently injects at 50 MeV into the PSB, and it will also represents the first step in the injector upgrade for the LHC aiming at increasing its luminosity. This paper reports on the status of the design and construction of the main machine elements, which will be installed in the linac tunnel from the beginning of 2012 onwards, on the progress of the civil engineering and on the ongoing activities at the Linac4 test stand.

  10. Energy status 2010; Energistatus 2010

    Energy Technology Data Exchange (ETDEWEB)

    Skaansar, Ellen

    2011-07-01

    In the new report, Energy Status NVE provides a unified presentation of statistics and facts about the Norwegian energy system. It gives an overview of the production, transmission and consumption of electricity in the Norwegian society, and shows energy use for various purposes and the relationship between energy and the environment. Norway is the sixth largest hydropower producer in the world and, together with Iceland the highest portion of renewable electricity production of all countries in Europe. In comparison, is about 17 percent of all electricity in the EU based on renewable resources. In Sweden, renewable energy resources account for about half of all electricity production, while the corresponding share in Denmark is about 29 percent. The good supply of water power has contributed to the fact that Norway has a consumption pattern that differs from the countries around us. (AG)

  11. Nuclear energy - status and outlook

    Energy Technology Data Exchange (ETDEWEB)

    Rogner, Hans-Holger; MacDonald, Alan

    2007-07-01

    Rising expectations best characterize the current prospects of nuclear power in a world that is confronted with a burgeoning demand for energy, higher energy prices, energy supply security concerns and growing environmental pressures. It appears that the inherent economic and environmental benefits of the technology and its excellent performance record over the last twenty years are beginning to tilt the balance of political opinion and public acceptance in favour of nuclear power. Nuclear power is a cost-effective supply-side technology for mitigating climate change and can make a substantial contribution to climate protection. This paper reviews the current status of nuclear power and its fuel cycle and provides an outlook on where nuclear power may be headed in the short-to-medium run (20 to 40 years from now). (auth)

  12. Diphtheria immunity status in Egypt.

    Science.gov (United States)

    Redwan, El-Rashdy M; El-Awady, Mostafa K

    2004-01-01

    The aim of this study was to determine immune status to corynebacterium diphtheria by screening for protective antibodies in a sample of Egyptian population. The study population consisted of 709 healthy subjects aged from 2 months to 105 years, inhabitants of 6 regions of Egypt. The study utilized Enzyme linked immunosorbent assay (ELISA) to measure serum levels IgG antibodies reactive with diphtheria toxoid. Levels of diphtheria toxoid antibody > or = 0.1 IU/ ml were defined as immune/protected, 23.9 % of the population were found to be susceptible to diphtheria (IgG level antibodies decreased in old ages (< 60 y) with the females being more susceptible then males. These results recommend a booster immunization for the susceptible age groups.

  13. Status of sterile neutrino oscillations

    Energy Technology Data Exchange (ETDEWEB)

    Schwetz, Thomas

    2013-02-15

    There are several independent hints for neutrino oscillations with a mass-squared difference at the eV{sup 2} scale. If confirmed, this would imply the existence of sterile neutrinos. I discuss the present status of the hints for ν{sub e} disappearance from reactor experiments and Gallium source experiments, as well as from the LSND and MiniBooNE ν{sub μ}→ν{sub e} appearance searches. A consistent interpretation of the global data in terms of neutrino oscillations is challenged by the non-observation of a positive signal in ν{sub μ} disappearance experiments. There is a strong tension in the global data, irrespective of the number of eV-scale neutrino states.

  14. LSST telescope and site status

    Science.gov (United States)

    Gressler, William J.

    2016-07-01

    The Large Synoptic Survey Telescope (LSST) Project1 received its construction authorization from the National Science Foundation in August 2014. The Telescope and Site (T and S) group has made considerable progress towards completion in subsystems required to support the scope of the LSST science mission. The LSST goal is to conduct a wide, fast, deep survey via a 3-mirror wide field of view optical design, a 3.2-Gpixel camera, and an automated data processing system. The summit facility is currently under construction on Cerro Pachón in Chile, with major vendor subsystem deliveries and integration planned over the next several years. This paper summarizes the status of the activities of the T and S group, tasked with design, analysis, and construction of the summit and base facilities and infrastructure necessary to control the survey, capture the light, and calibrate the data. All major telescope work package procurements have been awarded to vendors and are in varying stages of design and fabrication maturity and completion. The unique M1M3 primary/tertiary mirror polishing effort is completed and the mirror now resides in storage waiting future testing. Significant progress has been achieved on all the major telescope subsystems including the summit facility, telescope mount assembly, dome, hexapod and rotator systems, coating plant, base facility, and the calibration telescope. In parallel, in-house efforts including the software needed to control the observatory such as the scheduler and the active optics control, have also seen substantial advancement. The progress and status of these subsystems and future LSST plans during this construction phase are presented.

  15. Preliminary Integrated Safety Analysis Status Report

    Energy Technology Data Exchange (ETDEWEB)

    D. Gwyn

    2001-04-01

    This report provides the status of the potential Monitored Geologic Repository (MGR) Integrated Safety Analysis (EA) by identifying the initial work scope scheduled for completion during the ISA development period, the schedules associated with the tasks identified, safety analysis issues encountered, and a summary of accomplishments during the reporting period. This status covers the period from October 1, 2000 through March 30, 2001.

  16. The impact of migraine on health status

    NARCIS (Netherlands)

    Essink-Bot, M L; van Royen, L; Krabbe, P; Bonsel, G J; Rutten, F F

    1995-01-01

    PROBLEMS: What is the effect of migraine on health status, defined as the patient's physical, psychological, and social functioning? And, suppose that the health status of migraine sufferers appears to be impaired, to what extent is this a consequence of migraine-associated comorbidity rather than o

  17. Who values the status of the entrepreneur?

    NARCIS (Netherlands)

    van Praag, M.

    2009-01-01

    Parker and Van Praag (2009) showed, based on theory, that the group status of the profession 'entrepreneurship' shapes people's occupational preferences and thus their choice behavior. The current study focuses on the determinants and consequences of the group status of a profession, entrepreneurshi

  18. Advanced Skills Teachers: Professional Identity and Status

    Science.gov (United States)

    Fuller, C.; Goodwyn, A.; Francis-Brophy, E.

    2013-01-01

    The teaching profession continues to struggle with defining itself in relation to other professions. Even though public opinion positions teachers second only to doctors and nurses in terms of their professional status and prestige research in the UK suggests that teachers still believe that they have much lower status than other professions. With…

  19. 49 CFR 1572.105 - Immigration status.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 9 2010-10-01 2010-10-01 false Immigration status. 1572.105 Section 1572.105... ASSESSMENTS Standards for Security Threat Assessments § 1572.105 Immigration status. (a) An individual... to an order of removal under the immigration laws of the United States is not eligible to apply for...

  20. Status report of the HARP experiment

    CERN Document Server

    Catanesi, MG; Edgecock, R; Ellis, M; Soler, F J P; Gössling, C; Bunyatov, S; Krasnoperov, A; Popov, B; Serdiouk, V; Tereshchenko, V; Di Capua, E; Vidal-Sitjes, G; Artamonov, A; Giani, S; Gilardoni, S; Gorbunov, P; Grant, A; Grossheim, A; Ivanchenko, V; Kayis-Topaksu, A; Panman, J; Papadopoulos, I; Chernyaev, E; Tsukerman, I; Veenhof, R; Wiebusch, C; Zucchelli, P; Blondel, A; Borghi, S; Morone, M C; Prior, G; Schroeter, R; Meurer, C; Gastald, U; Mills, G B; Graulich, J S; Grégoire, G; Bonesini, M; Ferri, F; Kirsanov, M; Bagulya, A; Grichine, V; Polukhina, N; Palladino, V; Coney, L; Schmitz, D; Barr, G; De Santo, A; Bobisut, F; Gibin, D; Guglielmi, A; Mezzetto, M; Dore, J Dumarchez U; Orestano, D; Pastore, F; Tonazzo, A; Tortora, L; Booth, C; Howlett, L; Bogomilov, M; Chizhov, M; Kolev, D; Piperov, R Tsenov S; Temnikov, P; Apollonio, M; Chimenti, P; Giannini, G; Burguet-Castell, J; Cervera-Villanueva, Anselmo; Martín-Albo, J; Gómez-Cadenas, J J; Novella, P; Sorel, M

    2008-01-01

    The current status of the HARP experiment is shortly described, emphasizing the developments since the previous status report, which was presented in September 2007. The last section of this report is devoted to the comparisons of our large angle results with previously published data and some recent results of an alternative analysis performed by the so-called CDP group.

  1. Status Characteristics, Reward Allocation, and Equity

    Science.gov (United States)

    Parcel, Toby L.; Cook, Karen S.

    1977-01-01

    The relationship between a group's power and prestige or status hierarchy and group members' patterns of reward allocation was investigated. The addition of evidence concerning actual task performance results in the alignment of reward and status rankings and encourages the use of distribution rules stressing equity as opposed to equality.…

  2. Socioeconomic status and risk of rheumatoid arthritis

    DEFF Research Database (Denmark)

    Pedersen, Line Merete Blak; Jacobsen, Søren; Klarlund, Mette;

    2006-01-01

    To examine whether markers of socioeconomic status (SES) are associated with risk of rheumatoid arthritis (RA), and if so, whether selected lifestyle-related factors could explain this association.......To examine whether markers of socioeconomic status (SES) are associated with risk of rheumatoid arthritis (RA), and if so, whether selected lifestyle-related factors could explain this association....

  3. Preoperative Smoking Status and Postoperative Complications

    DEFF Research Database (Denmark)

    Grønkjær, Marie; Eliasen, Marie; Skov-Ettrup, Lise Skrubbeltrang;

    2014-01-01

    To systematically review and summarize the evidence of an association between preoperative smoking status and postoperative complications elaborated on complication type.......To systematically review and summarize the evidence of an association between preoperative smoking status and postoperative complications elaborated on complication type....

  4. Asynchronous ASCII Event Count Status Code

    Science.gov (United States)

    2012-03-01

    IRIG STANDARD 215-12 TELECOMMUNICATIONS AND TIMING GROUP ASYNCHRONOUS ASCII EVENT COUNT STATUS CODES...Inter-range Instrumentation Group ( IRIG ) Standard for American Standard Code for Information Interchange (ASCII)-formatted EC status transfer which can be...circuits and Ethernet networks. Provides systems engineers and equipment vendors with an Inter-range Instrumentation Group ( IRIG ) Standard for American

  5. Schedule and status of irradiation experiments

    Energy Technology Data Exchange (ETDEWEB)

    Rowcliffe, A.F.; Grossbeck, M.L. [Oak Ridge National Lab., TN (United States)

    1997-04-01

    To provide an updated summary of the status of irradiation experiments for the neutron-interactive materials program. The current status of reactor irradiation experiments is presented in tables summarizing the experimental objectives, conditions, and schedule. Currently, the program has two irradiation experiments in reactor; and 8 experiments in the planning or design stages. Postirradiation examination and testing is in progress on 18 experiments.

  6. Materialism, status consumption, and consumer independence.

    Science.gov (United States)

    Goldsmith, Ronald Earl; Clark, Ronald A

    2012-01-01

    Materialism influences many people. We focus on two aspects of this influence: reactions to prestige products and to the influence of others. A study of 187 U.S. student consumers shows that materialism is positively related to buying products that confer status. In contrast, materialism is negatively related to consumer independence, an enduring tendency to pay minimal attention to the prescribed norms of other consumers and to make product and brand decisions according to personal preferences. Consuming products for status is also negatively related to consumer independence. Moreover, the association between materialism and consumer independence is completely mediated by consuming for status. Materialism urges consumers to be status conscious so that they follow social norms in purchasing, but seeking status through goods is avoided by less materialistic, independent consumers. A second study (n = 258) also using student consumers confirmed these results.

  7. The influence of status on satisfaction with relative rewards

    DEFF Research Database (Denmark)

    Albrecht, Konstanze; Essen, Emma von; Falk, Armin;

    2014-01-01

    This study investigates how induced relative status affects satisfaction with different relative payoffs. We find that participants with lower status are more satisfied with disadvantageous payoff inequalities than equal or higher status participants. In contrast, when receiving an advantageous...... payoff, status does not affect satisfaction. Our findings suggest that relative social status has important implications for the acceptance of income inequalities....

  8. ESA CHEOPS mission: development status

    Science.gov (United States)

    Rando, N.; Asquier, J.; Corral Van Damme, C.; Isaak, K.; Ratti, F.; Safa, F.; Southworth, R.; Broeg, C.; Benz, W.

    2016-07-01

    The European Space Agency (ESA) Science Programme Committee (SPC) selected CHEOPS (Characterizing Exoplanets Satellite) in October 2012 as the first S-class mission (S1) within the Agency's Scientific Programme, targeting launch readiness by the end of 2017. The CHEOPS mission is devoted to the first-step characterization of known exoplanets orbiting bright stars, to be achieved through the precise measurement of exo-planet radii using the technique of transit photometry. It is implemented as a partnership between ESA and a consortium of Member States led by Switzerland. CHEOPS is considered as a pilot case for implementing "small science missions" in ESA with the following requirements: science driven missions selected through an open Call for missions (bottom-up process); spacecraft development schedule much shorter than for M and L missions, in the range of 4 years; and cost-capped missions to ESA with possibly higher Member States involvement than for M or L missions. The paper describes the CHEOPS development status, focusing on the performed hardware manufacturing and test activities.

  9. Current status of Japanese detectors

    CERN Document Server

    Tatsumi, Daisuke; Arai, Koji; Nakagawa, Noriyasu; Agatsuma, Kazuhiro; Yamazaki, Toshitaka; Fukushima, Mitsuhiro; Fujimoto, Masa-Katsu; Takamori, Akiteru; Bertolini, Alessandro; Sannibale, Virginio; DeSalvo, Riccardo; Marka, Szabolcs; Ando, Masaki; Tsubono, Kimio; Akutsu, Tomomi; Yamamoto, Kazuhiro; Ishitsuka, Hideki; Uchiyama, Takashi; Miyoki, Shinji; Ohashi, Masatake; Kuroda, Kazuaki; Awaya, Norichika; Kanda, Nobuyuki; Araya, Akito; Telada, Souichi; Tomaru, Takayuki; Haruyama, Tomiyoshi; Yamamoto, Akira; Sato, Nobuaki; Suzuki, Toshitaka; Shintomi, Takakazu

    2007-01-01

    Current status of TAMA and CLIO detectors in Japan is reported in this article. These two interferometric gravitational-wave detectors are being developed for the large cryogenic gravitational wave telescope (LCGT) which is a future plan for detecting gravitational wave signals at least once per year. TAMA300 is being upgraded to improve the sensitivity in low frequency region after the last observation experiment in 2004. To reduce the seismic noises, we are installing new seismic isolation system, which is called TAMA Seismic Attenuation System, for the four test masses. We confirmed stable mass locks of a cavity and improvements of length and angular fluctuations by using two SASs. We are currently optimizing the performance of the third and fourth SASs. We continue TAMA300 operation and R&D studies for LCGT. Next data taking in the summer of 2007 is planned. CLIO is a 100-m baseline length prototype detector for LCGT to investigate interferometer performance in cryogenic condition. The key features of...

  10. Mineral Status of Myocardial Sarcocystosis

    Directory of Open Access Journals (Sweden)

    GA Kojouri

    2011-06-01

    Full Text Available Background: The role of minerals on parasite persistency and the interaction between minerals and animal responses to the parasite infestation is not clear. For these reasons, the present re­search was aimed to compare copper, zinc and iron status in sheep with parasitic myocarditis and healthy ones in 2009.Methods: Blood and heart tissue samples were collected from 145 slaughtered sheep and histopa­thological findings were confirmed as myocardial sarcocystosis in 27 cases. Serum and tis­sue mineral level were determined by atomic absorption spectroscopy. Data were analyzed by Sig­mastat program, using One Way Analysis of Variance (ANOVA at the level of P<0.05.Results: Myocardial sarcocystosis significantly increase myocardial concentration of Cu, Zn and Fe (P<0.05.Conclusion: These findings may explain the role of copper, zinc and iron in parasite persistency and may discuss the pathogenesis of sarcocystosis, which relates to evocate mentioned micronutri­ent to cardiac muscle.

  11. Aging, Nutritional Status and Health

    Directory of Open Access Journals (Sweden)

    Wilma Leslie

    2015-07-01

    Full Text Available The older population is increasing worldwide and in many countries older people will outnumber younger people in the near future. This projected growth in the older population has the potential to place significant burdens on healthcare and support services. Meeting the diet and nutrition needs of older people is therefore crucial for the maintenance of health, functional independence and quality of life. While many older adults remain healthy and eat well those in poorer health may experience difficulties in meeting their nutritional needs. Malnutrition, encompassing both under and over nutrition increases health risks in the older population. More recently the increase in obesity, and in turn the incidence of chronic disease in older adults, now justifies weight management interventions in obese older adults. This growing population group is becoming increasingly diverse in their nutritional requirements. Micro-nutrient status may fluctuate and shortfalls in vitamin D, iron and a number of other nutrients are relatively common and can impact on well-being and quality of life. Aging presents a number of challenges for the maintenance of good nutritional health in older adults.

  12. Caffeine, cognition, and socioeconomic status.

    Science.gov (United States)

    Kyle, Janet; Fox, Helen C; Whalley, Lawrence J

    2010-01-01

    There is interest in age-related cognitive decline and environmental risk factors for Alzheimer's disease (AD). This interest is focused on individual differences in exposure to agents that may harm or protect cognitive function. Caffeine is used as a short acting mental stimulant and may possess longer-term properties that protect against age-related decline and, possibly, AD. The current study aimed to: 1) examine current cognitive function in a narrow age range sample (n=351) without dementia (MMSE>25) who are, by reason of age, entering the period of increased risk of AD; and 2) link cognitive function to self-reported intake of caffeine and socioeconomic status (SES). Possible confounding by gender, childhood intelligence, education, and symptoms of anxiety and depression was introduced into the statistical model. There were significant differences between SES groups in caffeine intake (pcognitive performance (pcaffeine intake were associated with slower digit symbol speed (F =3.38, pcaffeine during cognitive testing and strong links between SES and cognitive performance. No evidence in support of cognitive enhancing effects of caffeine was found.

  13. Sinoprobe Datacenter Development: Current Status

    Science.gov (United States)

    Guan, Y.; Dong, S.; Chen, Z.; Chen, G.; Cheng, M.

    2011-12-01

    The project of the Sinoprobe datacenter development is to build new IT infrastructures needed to store, visualize and manage all the data acquired by SinoProbe program.The SinoProbe data center is designed using service-oriented architecture (SOA) principles. More specifically, service component architecture (SCA) is used to implement sinoprobe data services. It also uses various advanced technologies such as Java/JEE for the platform, PostgresSQL/PostGIS for the data storage, ApacheDS for LDAP, CoachDB for the medadata storage, GeoServer for the GIS services, ExtJs and OpenLayer for the Ajax framework, and Apache Shiro for the security framework. Through the integration and development of various technologies used, the major services of the datacenter system are implemented including the security infrastructure services (user authentication and authorization), metadata services, data warehouse stores, data services, GIS services, and web portal. There are also visualization components including the development of a virtual globe to replace the currently used Google Earth. This poster presents the current status of the SinoProbe data center development, and the detailed discussion of the system.

  14. Vitamin D Status in Korea

    Directory of Open Access Journals (Sweden)

    Han Seok Choi

    2013-03-01

    Full Text Available The majority of the vitamin D in our body is produced by cutaneous synthesis in response to sunlight. As more and more people live in cities and spend the bulk of their time indoors, it can be difficult to get sufficient sun exposure for adequate cutaneous production of vitamin D. Therefore, vitamin D insufficiency has become a very common health problem worldwide. The Korea National Health and Nutrition Examination Survey IV 2008 showed that the prevalence of vitamin D insufficiency, defined as a serum 25-hydroxyvitamin D [25(OHD] level below 50 nmol/L, was 47.3% in males and 64.5% in females. Only 13.2% of males and 6.7% of females had a serum 25(OHD level of greater than 75 nmol/L. In Korea, vitamin D insufficiency was more prevalent in young adults than in elderly people, likely due to the indoor lifestyle of younger people. Compared with the United States and Canada, Korea has a lower mean 25(OHD level and a higher prevalence of vitamin D insufficiency. To improve the vitamin D status of the Korean population, more aggressive policies on food fortification and vitamin D supplementation are needed.

  15. Environmental status 2009; Miljoestatus 2009

    Energy Technology Data Exchange (ETDEWEB)

    2009-07-01

    The environment and climate has in recent years received their deserved place high on the public agenda. Still many important issues and contexts make little or no attention in the debates. As environmental directorates one of the most important tasks is to contribute reliable, relevant and understandable information about the state of the environment and development. Environmental status 2009 provides a thematic and comprehensive overview of environmental challenges in Norway. Where are we today, and what are the biggest challenges ahead? What are the national goals? And what have we achieved? The information is based on facts and analysis from their own work and from various research and knowledge communities co-working with the directorate.Climate change has been given much space because it is the biggest threat to the environment. Loss of biological diversity - a major problem compounded by climate change - and the fight against environmental toxins that affect animal and human health, are also high priority. Directorate for Nature Management and Norwegian Pollution Control Authority are responsible for the report and the contents of the chapters on biodiversity and pollution. The chapter on cultural heritage is written by the Cultural Heritage. (AG)

  16. Utility photovoltaic group: Status report

    Science.gov (United States)

    Serfass, Jeffrey A.; Hester, Stephen L.; Wills, Bethany N.

    1996-01-01

    The Utility PhotoVoltaic Group (UPVG) was formed in October of 1992 with a mission to accelerate the use of cost-effective small-scale and emerging grid-connected applications of photovoltaics for the benefit of electric utilities and their customers. The UPVG is now implementing a program to install up to 50 megawatts of photovoltaics in small-scale and grid-connected applications. This program, called TEAM-UP, is a partnership of the U.S. electric utility industry and the U.S. Department of Energy to help develop utility PV markets. TEAM-UP is a utility-directed program to significantly increase utility PV experience by promoting installations of utility PV systems. Two primary program areas are proposed for TEAM-UP: (1) Small-Scale Applications (SSA)—an initiative to aggregate utility purchases of small-scale, grid-independent applications; and (2) Grid-Connected Applications (GCA)—an initiative to identify and competitively award cost-sharing contracts for grid-connected PV systems with high market growth potential, or collective purchase programs involving multiple buyers. This paper describes these programs and outlines the schedule, the procurement status, and the results of the TEAM-UP process.

  17. Status of US ITER Diagnostics

    Science.gov (United States)

    Stratton, B.; Delgado-Aparicio, L.; Hill, K.; Johnson, D.; Pablant, N.; Barnsley, R.; Bertschinger, G.; de Bock, M. F. M.; Reichle, R.; Udintsev, V. S.; Watts, C.; Austin, M.; Phillips, P.; Beiersdorfer, P.; Biewer, T. M.; Hanson, G.; Klepper, C. C.; Carlstrom, T.; van Zeeland, M. A.; Brower, D.; Doyle, E.; Peebles, A.; Ellis, R.; Levinton, F.; Yuh, H.

    2013-10-01

    The US is providing 7 diagnostics to ITER: the Upper Visible/IR cameras, the Low Field Side Reflectometer, the Motional Stark Effect diagnostic, the Electron Cyclotron Emission diagnostic, the Toroidal Interferometer/Polarimeter, the Core Imaging X-Ray Spectrometer, and the Diagnostic Residual Gas Analyzer. The front-end components of these systems must operate with high reliability in conditions of long pulse operation, high neutron and gamma fluxes, very high neutron fluence, significant neutron heating (up to 7 MW/m3) , large radiant and charge exchange heat flux (0.35 MW/m2) , and high electromagnetic loads. Opportunities for repair and maintenance of these components will be limited. These conditions lead to significant challenges for the design of the diagnostics. Space constraints, provision of adequate radiation shielding, and development of repair and maintenance strategies are challenges for diagnostic integration into the port plugs that also affect diagnostic design. The current status of design of the US ITER diagnostics is presented and R&D needs are identified. Supported by DOE contracts DE-AC02-09CH11466 (PPPL) and DE-AC05-00OR22725 (UT-Battelle, LLC).

  18. Space Shuttle Strategic Planning Status

    Science.gov (United States)

    Norbraten, Gordon L.; Henderson, Edward M.

    2007-01-01

    The Space Shuttle Program is aggressively flying the Space Shuttle manifest for assembling the International Space Station and servicing the Hubble Space Telescope. Completing this flight manifest while concurrently transitioning to the Exploration architecture creates formidable challenges; the most notable of which is retaining critical skills within the Shuttle Program workforce. The Program must define a strategy that will allow safe and efficient fly-out of the Shuttle, while smoothly transitioning Shuttle assets (both human and facility) to support early flight demonstrations required in the development of NASA's Crew Exploration Vehicle (Orion) and Crew and Cargo Launch Vehicles (Ares I). The Program must accomplish all of this while maintaining the current level of resources. Therefore, it will be necessary to initiate major changes in operations and contracting. Overcoming these challenges will be essential for NASA to fly the Shuttle safely, accomplish the Vision for Space Exploration, and ultimately meet the national goal of maintaining a robust space program. This paper will address the Space Shuttle Program s strategy and its current status in meeting these challenges.

  19. Industry outreach a status report

    Energy Technology Data Exchange (ETDEWEB)

    Surek, D.; Sen, R. [R.K. Sen & Associates, Inc., Bethesda, MD (United States)

    1995-09-01

    The Outreach Project was initiated in October 1994 with the objective of developing a multi-year plan for the U.S. Department of Energy (DOE) for targeted outreach activities for stakeholders in industry and the general public. This status report summarizes the work on industry outreach that has been completed since the inception of the project in October 1994. A three-pronged approach was taken to ascertain issues related to industry outreach. First, there was a review of on-going and past industry outreach activities at DOE and NHA. Next, a series of meetings with industry decision makers was arranged to get a better understanding of industry interests and concerns, and to discuss how DOE and industry could work collaboratively to develop hydrogen energy systems. Third, a workshop is scheduled where representatives from industry, DOE and other federal agencies can identify issues that would enhance partnering between the federal government and industry in the development of hydrogen energy systems. At this tiny, the review of on-going and past activities has been completed. Industry interviews are in progress and a majority of meetings have been held. Analysis of the information gained is in progress. The preliminary analysis of this information indicates that for appropriate near-term demonstration-type projects, the level of interest for collaboration between DOE and industry is high. The data also identifies issues industry is concerned with which impact the commercialization of hydrogen energy systems.

  20. Primary status, complementary status, and organizational survival in the U.S. venture capital industry.

    Science.gov (United States)

    Bothner, Matthew S; Kim, Young-Kyu; Lee, Wonjae

    2015-07-01

    We introduce a distinction between two kinds of status and examine their effects on the exit rates of organizations investing in the U.S. venture capital industry. Extending past work on status-based competition, we start with a simple baseline: we describe primary status as a network-related signal of an organization's quality in a leadership role, that is, as a function of the degree to which an organization leads others that are themselves well regarded as lead organizations in the context of investment syndicates. Combining Harary's (1959) image of the elite consultant with Goffman's (1956) concept of "capacity-esteem," we then discuss complementary status as an affiliation-based signal of an organization's quality in a supporting role. We measure complementary status as a function of the extent to which an organization is invited into syndicates by well-regarded lead organizations-that is, by those possessing high levels of primary status. Findings show that, conditioning on primary status, complementary status reduces the rate at which venture capital organizations exit the industry. Consistent with the premise that these kinds of status correspond to different roles and market identities, we also find that complementary status attenuates (and ultimately reverses) the otherwise favorable effect of primary status on an organization's life chances. Theoretically and methodologically oriented scope conditions, as well as implications for future research, are discussed.

  1. Current Trends in Treatment of Status Epilepticus and Refractory Status Epilepticus.

    Science.gov (United States)

    Betjemann, John P

    2015-12-01

    Status epilepticus is a heterogeneous disorder with varied definitions and presentations. Taken together, all forms of status epilepticus carry significant morbidity and mortality, much of which is dictated by the underlying etiology. Generalized convulsive status epilepticus, which represents a common form, is a true neurologic emergency that requires emergent management. Treatment focuses on stabilizing the patient and aggressive medical management to achieve the timely termination of seizures. For other forms of status epilepticus including nonconvulsive and focal status epilepticus, the goal remains early seizure termination, but the use of intravenous medications should be weighed against the risks associated with these therapies. The diagnostic evaluation of status epilepticus is guided by the patient's history and should be broad, including a screen for toxins, electrolytes, structural abnormalities, and central nervous system infectious and autoimmune/inflammatory etiologies. Considerable research is still needed to improve our understanding of the mechanisms, consequences, and therapy of status epilepticus.

  2. Genetic mutations associated with status epilepticus.

    Science.gov (United States)

    Bhatnagar, M; Shorvon, S

    2015-08-01

    This paper reports the results of a preliminary search of the literature aimed at identifying the genetic mutations reported to be strongly associated with status epilepticus. Genetic mutations were selected for inclusion if status epilepticus was specifically mentioned as a consequence of the mutation in standard genetic databases or in a case report or review article. Mutations in 122 genes were identified. The genetic mutations identified were found in only rare conditions (sometimes vanishingly rare) and mostly in infants and young children with multiple other handicaps. Most of the genetic mutations can be subdivided into those associated with cortical dysplasias, inborn errors of metabolism, mitochondrial disease, or epileptic encephalopathies and childhood syndromes. There are no identified 'pure status epilepticus genes'. The range of genes underpinning status epilepticus differs in many ways from the range of genes underpinning epilepsy, which suggests that the processes underpinning status epilepticus differ from those underpinning epilepsy. It has been frequently postulated that status epilepticus is the result of a failure of 'seizure termination mechanisms', but the wide variety of genes affecting very diverse biochemical pathways identified in this survey makes any unitary cause unlikely. The genetic influences in status epilepticus are likely to involve a wide range of mechanisms, some related to development, some to cerebral energy production, some to diverse altered biochemical pathways, some to transmitter and membrane function, and some to defects in networks or systems. The fact that many of the identified genes are involved with cerebral development suggests that status epilepticus might often be a system or network phenomenon. To date, there are very few genes identified which are associated with adult-onset status epilepticus (except in those with preexisting neurological damage), and this is disappointing as the cause of many adult

  3. Decoupling social status and status certainty effects on health in macaques: a network approach

    Science.gov (United States)

    Hannibal, Darcy L.; Nathman, Amy C.; Capitanio, John P.; Hsieh, Fushing; Atwill, Edward R.; McCowan, Brenda

    2016-01-01

    Background Although a wealth of literature points to the importance of social factors on health, a detailed understanding of the complex interplay between social and biological systems is lacking. Social status is one aspect of social life that is made up of multiple structural (humans: income, education; animals: mating system, dominance rank) and relational components (perceived social status, dominance interactions). In a nonhuman primate model we use novel network techniques to decouple two components of social status, dominance rank (a commonly used measure of social status in animal models) and dominance certainty (the relative certainty vs. ambiguity of an individual’s status), allowing for a more complex examination of how social status impacts health. Methods Behavioral observations were conducted on three outdoor captive groups of rhesus macaques (N = 252 subjects). Subjects’ general physical health (diarrhea) was assessed twice weekly, and blood was drawn once to assess biomarkers of inflammation (interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and C-reactive protein (CRP)). Results Dominance rank alone did not fully account for the complex way that social status exerted its effect on health. Instead, dominance certainty modified the impact of rank on biomarkers of inflammation. Specifically, high-ranked animals with more ambiguous status relationships had higher levels of inflammation than low-ranked animals, whereas little effect of rank was seen for animals with more certain status relationships. The impact of status on physical health was more straightforward: individuals with more ambiguous status relationships had more frequent diarrhea; there was marginal evidence that high-ranked animals had less frequent diarrhea. Discussion Social status has a complex and multi-faceted impact on individual health. Our work suggests an important role of uncertainty in one’s social status in status-health research. This work also suggests that

  4. Decoupling social status and status certainty effects on health in macaques: a network approach

    Directory of Open Access Journals (Sweden)

    Jessica J. Vandeleest

    2016-09-01

    Full Text Available Background Although a wealth of literature points to the importance of social factors on health, a detailed understanding of the complex interplay between social and biological systems is lacking. Social status is one aspect of social life that is made up of multiple structural (humans: income, education; animals: mating system, dominance rank and relational components (perceived social status, dominance interactions. In a nonhuman primate model we use novel network techniques to decouple two components of social status, dominance rank (a commonly used measure of social status in animal models and dominance certainty (the relative certainty vs. ambiguity of an individual’s status, allowing for a more complex examination of how social status impacts health. Methods Behavioral observations were conducted on three outdoor captive groups of rhesus macaques (N = 252 subjects. Subjects’ general physical health (diarrhea was assessed twice weekly, and blood was drawn once to assess biomarkers of inflammation (interleukin-6 (IL-6, tumor necrosis factor-alpha (TNF-α, and C-reactive protein (CRP. Results Dominance rank alone did not fully account for the complex way that social status exerted its effect on health. Instead, dominance certainty modified the impact of rank on biomarkers of inflammation. Specifically, high-ranked animals with more ambiguous status relationships had higher levels of inflammation than low-ranked animals, whereas little effect of rank was seen for animals with more certain status relationships. The impact of status on physical health was more straightforward: individuals with more ambiguous status relationships had more frequent diarrhea; there was marginal evidence that high-ranked animals had less frequent diarrhea. Discussion Social status has a complex and multi-faceted impact on individual health. Our work suggests an important role of uncertainty in one’s social status in status-health research. This work also

  5. PKIX Certificate Status in Hybrid MANETs

    Science.gov (United States)

    Muñoz, Jose L.; Esparza, Oscar; Gañán, Carlos; Parra-Arnau, Javier

    Certificate status validation is a hard problem in general but it is particularly complex in Mobile Ad-hoc Networks (MANETs) because we require solutions to manage both the lack of fixed infrastructure inside the MANET and the possible absence of connectivity to trusted authorities when the certification validation has to be performed. In this sense, certificate acquisition is usually assumed as an initialization phase. However, certificate validation is a critical operation since the node needs to check the validity of certificates in real-time, that is, when a particular certificate is going to be used. In such MANET environments, it may happen that the node is placed in a part of the network that is disconnected from the source of status data at the moment the status checking is required. Proposals in the literature suggest the use of caching mechanisms so that the node itself or a neighbour node has some status checking material (typically on-line status responses or lists of revoked certificates). However, to the best of our knowledge the only criterion to evaluate the cached (obsolete) material is the time. In this paper, we analyse how to deploy a certificate status checking PKI service for hybrid MANET and we propose a new criterion based on risk to evaluate cached status data that is much more appropriate and absolute than time because it takes into account the revocation process.

  6. Smart-1 Project Development Status

    Science.gov (United States)

    Racca, G. D.; Foing, B. H.; SMART-1 Project Team

    SMART-1 is the first of the Small Missions for Advanced Research in Technology of the ESA Horizons 2000 Science Plan. The main mission objective of SMART-1 is to demonstrate key technologies for Bepi-Colombo and other scientific deep-space missions. One of the key technologies is the solar electric propulsion used as primary propulsion. The electric propulsion will be using 1400W to transfer the 350 kg space- craft from an Ariane-5 standard GTO to an elliptic Moon polar orbit, 10000x300 km. The total mission time is 24 months including a maximum of 18 months transfer time. The spacecraft development entered the detailed design and implementation phase in October 1999, under the responsibility of the Swedish Space Corporation as prime contractor, and the flight acceptance is targeted for the end of 2002. Apart from the in-orbit demonstration of electric propulsion as primary propulsion, SMART-1 is im- plementing many other enabling technologies for deep-space missions. In addition, the spacecraft avionics design is tailored to the low cost philosophy by enabling flexi- ble integration of Commercial Off The Shelf (COTS) equipment. The scientific instru- ments support the characterisation of the electric propulsion thrust environment during the long transfer phase and detailed imaging and spectroscopy of the lunar surface in visible, infrared and X-ray during the Moon orbiting phase. The paper summarises the baseline mission and spacecraft design. The main part of the paper highlights the spacecraft design status and the assembly, integration and verification activities.

  7. SEMATECH EUVL mask program status

    Science.gov (United States)

    Yun, Henry; Goodwin, Frank; Huh, Sungmin; Orvek, Kevin; Cha, Brian; Rastegar, Abbas; Kearney, Patrick

    2009-04-01

    As we approach the 22nm half-pitch (hp) technology node, the industry is rapidly running out of patterning options. Of the several lithography techniques highlighted in the International Technology Roadmap for Semiconductors (ITRS), the leading contender for the 22nm hp insertion is extreme ultraviolet lithography (EUVL). Despite recent advances with EUV resist and improvements in source power, achieving defect free EUV mask blank and enabling the EUV mask infrastructure still remain critical issues. To meet the desired EUV high volume manufacturing (HVM) insertion target date of 2013, these obstacles must be resolved on a timely bases. Many of the EUV mask related challenges remain in the pre-competitive stage and a collaborative industry based consortia, such as SEMATECH can play an important role to enable the EUVL landscape. SEMATECH based in Albany, NY is an international consortium representing several of the largest manufacturers in the semiconductor market. Full members include Intel, Samsung, AMD, IBM, Panasonic, HP, TI, UMC, CNSE (College of Nanoscience and Engineering), and Fuller Road Management. Within the SEMATECH lithography division a major thrust is centered on enabling the EUVL ecosystem from mask development, EUV resist development and addressing EUV manufacturability concerns. An important area of focus for the SEMATECH mask program has been the Mask Blank Development Center (MBDC). At the MBDC key issues in EUV blank development such as defect reduction and inspection capabilities are actively pursued together with research partners, key suppliers and member companies. In addition the mask program continues a successful track record of working with the mask community to manage and fund critical mask tools programs. This paper will highlight recent status of mask projects and longer term strategic direction at the MBDC. It is important that mask technology be ready to support pilot line development HVM by 2013. In several areas progress has been

  8. Planet Hunters: A Status Report

    Science.gov (United States)

    Schwamb, Megan E.; Orosz, J. A.; Carter, J. A.; Fischer, D. A.; Howard, A. W.; Crepp, J. R.; Welsh, W. F.; Kaib, N. A.; Lintott, C. J.; Terrell, D.; Jek, K. J.; Gagliano, R.; Parrish, M.; Smith, A. M.; Lynn, S.; Brewer, J. M.; Giguere, M. J.; Schawinski, K.; Simpson, R. J.

    2012-10-01

    The Planet Hunters (http://www.planethunters.org) citizen science project uses the power of human pattern recognition via the World Wide Web to identify transits in the Kepler public data. Planet Hunters uses the Zooniverse (http://www.zooniverse.org) platform to present visitors to the Planet Hunters website with a randomly selected 30-day light curve segment from one of Kepler's 160,000 target stars. Volunteers are asked to draw boxes to mark the locations of visible transits with multiple independent classifiers reviewing each 30-day light curve segment. Since December 2010, more than 170,000 members of the general public have participated in Planet Hunters contributing over 12.5 million classifications searching the 1 1/2 years of publicly released Kepler observations. Planet Hunters is a novel and complementary technique to the automated transit detection algorithms, providing an independent assessment of the completeness of the Kepler exoplanet inventory. We report the latest results from Planet Hunters, highlighting in particular our latest efforts to search for circumbinary planets (planets orbiting a binary star) and single transit events in the first 1.5 years of public Kepler data. We will present a status report of our search of the first 6 Quarters of Kepler data, introducing our new planet candidates and sharing the results of our observational follow-up campaign to characterize these planetary systems. Acknowledgements: MES is supported by a NSF Astronomy and Astrophysics Postdoctoral Fellowship under award AST-1003258. This is research is supported in part by an American Philosophical Society Franklin Grant.

  9. Mars 2020 Planetary Protection Status

    Science.gov (United States)

    Stricker, Moogega; Bernard, Douglas; Benardini, James Nick; Jones, Melissa

    2016-07-01

    The Mars 2020 (M2020) flight system consists of a cruise stage; an entry, descent and landing system (EDL); and a Radioisotope Thermoelectric Generator (RTG) powered roving science vehicle that will land on the surface of Mars. The M2020 Mission is designed to investigate key question related to the habitability of Mars and will conduct assessments that set the stage for potential future human exploration of Mars. Per its Program Level Requirements, the project will also acquire and cache samples of rock, regolith, and/or procedural "blank" samples for possible return to Earth by a subsequent mission. NASA has assigned the M2020 Mission as a Category V Restricted Earth Return due to the possible future return of collected samples. As indicated in NPR8020.12D, Section 5.3.3.2, the outbound leg of a Category V mission that could potentially return samples to Earth, Mars 2020 would be expected to meet the requirements of a Category IVb mission. The entire flight system is subject to microbial reduction requirements, with additional specific emphasis on the sample acquisition and caching. A bioburden accounting tool is being used to track the microbial population on the surfaces to ensure that the biological cleanliness requirements are met. Initial bioburden estimates based on MSL heritage allows M2020 to gauge more precisely how the bioburden is allocated throughout each hardware element. Mars 2020 has completed a Planetary Protection Plan with Planetary Implementation Plans at a mature draft form. Planetary protection sampling activities have commenced with the start of flight system fabrication and assembly. The status of the Planetary Protection activities will be reported.

  10. Is an ethical status confessionis possible?

    Directory of Open Access Journals (Sweden)

    Alfred Rauhaus

    2009-11-01

    Full Text Available This article argues that it is possible to declare a status confessionis on account of ethical issues. Discussions of the last 50 years confirm this. The article clarifies under what circumstances a status confessionis may be declared. It is always necessary to indicate clearly that the confession of the church is affected by the ethical situation in question. It is not suffi cient to give a general reference to the gospel or to the teaching of Christ as the reason for declaring a status confessionis.

  11. Selenium and magnesium status in fibromyalgia.

    Science.gov (United States)

    Eisinger, J; Plantamura, A; Marie, P A; Ayavou, T

    1994-12-01

    Muscle pain has been associated with magnesium (Mg) and selenium (Se) deficiency: magnesium and selenium status were investigated in fibromyalgia (FM). Erythrocyte (E), leucocyte (L) and serum (S) magnesium, serum selenium and zinc, and vitamin B1, B2, A or E status were assessed in 22 patients with fibromyalgia and in 23 age-matched healthy controls. LMg is significantly increased (P fibromyalgia. These magnesium abnormalities are associated with previously-reported impairment of thiamin metabolism. Antioxidant status (as well as plasma malondialdehyde) is unchanged in fibromyalgia and serum selenium levels, slightly but not significantly correlated with serum magnesium, is normal.

  12. Status and recent highlights from ATLAS

    CERN Document Server

    Wengler, Thorsten; The ATLAS collaboration

    2016-01-01

    After a brief introduction the start-up of the ATLAS detector for 2016 data taking will be described, as well as its current status and performance, before discussing a selection of recent physics highlights.

  13. NPScape Metric GIS Data - Conservation Status

    Data.gov (United States)

    National Park Service, Department of the Interior — NPScape conservation status metrics are calculated using data from the USGS Gap Analysis Program (PAD-US), World Protected Areas Database (WDPA), and National Marine...

  14. Status of the MAJORANA DEMONSTRATOR experiment

    CERN Document Server

    Martin, R D; Aguayo, E; Avignone, F T; Barabash, A S; Bertrand, F E; Boswell, M; Brudanin, V; Busch, M; Caldwell, A S; Chan, Y-D; Christofferson, C D; Combs, D C; Detwiler, J A; Doe, P J; Efremenko, Yu; Egorov, V; Ejiri, H; Elliott, S R; Esterline, J; Fast, J E; Finnerty, P; Fraenkle, F M; Galindo-Uribarri, A; Giovanetti, G K; Goett, J; Green, M P; Gruszko, J; Guiseppe, V E; Gusev, K; Hallin, A L; Hazama, R; Hegai, A; Henning, R; Hoppe, E W; Howard, S; Howe, M A; Keeter, K J; Kidd, M F; Kochetov, O; Konovalov, S I; Kouzes, R T; LaFerriere, B D; Leon, J; Leviner, L E; Loach, J C; MacMullin, J; MacMullin, S; Mertens, S; Mizouni, L; Nomachi, M; Orrell, J L; O'Shaughnessy, C; Overman, N R; Phillips, D G; Poon, A W P; Pushkin, K; Radford, D C; Rielage, K; Robertson, R G H; Romero-Romero, E; Ronquest, M C; Schubert, A G; Shanks, B; Shima, T; Shirchenko, M; Snavely, K J; Snyder, N; Soin, A; Suriano, A M; Thompson, J; Timkin, V; Tornow, W; Varner, R L; Vasilyev, S; Vetter, K; Vorren, K; White, B R; Wilkerson, J F; Xu, W; Yakushev, E; Young, A R; Yu, C -H; Yumatov, V

    2013-01-01

    The MAJORANA DEMONSTRATOR neutrinoless double beta-decay experiment is currently under construction at the Sanford Underground Research Facility in South Dakota, USA. An overview and status of the experiment are given.

  15. Status of six endangered California Butterflies 1977

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — A survey was conducted from March-September 1977 to determine the current status of six federally endangered butterflies which reside in California. The butterflies...

  16. Nutritional Status in Self-Neglecting Elderly

    Science.gov (United States)

    Oliver, S. Mathews; Kelly, P. A.; Pickens, S.; Burnett, J.; Dyer, C. B.; Smith, S. M.

    2006-01-01

    Elder self-neglect is the most common, and most compelling form of elder mistreatment. Individuals who cannot provide the basic needs for themselves may develop social, functional, and physical deficits. The CREST project has the goal of systematically characterizing these individuals, and the objective of the study reported here is to characterize aspects of their nutritional status. Self-neglect (SN) subjects referred from Adult Protective Services were recruited and consented. Control (CN) subjects were matched for age, gender, race, and socio-economic status when possible. Reported here are data on 47 SN subjects (age 77 +/- 7, mean +/- SD; body weight 76 kg +/- 26) and 40 CN subjects (77 +/- 7, 79 kg +/- 20). Blood samples were analyzed for indices of nutritional status. SN subjects had higher serum concentrations of homocysteine (p elderly population is at risk with respect to several markers of nutritional status.

  17. Small $x$ Phenomenology - Summary and status 2002

    CERN Document Server

    Andersen, J R; Collins, J; Dokshitzer, Y; Görlich, L; Grindhammer, G; Gustafson, G; Jönsson, L B; Jung, H; Kwiecinski, J; Levin, E; Lipatov, A V; Lönnblad, L; Lublinsky, M; Maul, M; Milcewicz, I; Miu, G; Nowak, G; Sjöstrand, Torbjörn; Stasto, A M; Tîmneanu, N; Turnau, J; Zotov, N P

    2003-01-01

    A second workshop on small x physics, within the Small x Collaboration, was held in Lund in June 2002 with the aim of over-viewing recent theoretical progress in this area and summarizing the experimental status.

  18. Epidemiology of Status Epilepticus in Children

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2007-09-01

    Full Text Available The incidence, etiology, seizure characteristics, and outcome in childhood convulsive status epilepticus (CSE are reviewed by researchers from Great Ormond Street Hospital for Children, and the Institute of Child Health, London, UK.

  19. US Forest Service Wilderness Areas: Legal Status

    Data.gov (United States)

    US Forest Service, Department of Agriculture — A map service on the www depicting status of parcels for Forest Service land congressionally designated as wilderness such as National Wilderness Areas. This map...

  20. Damage Tensor Analysis on Regional Seismic Status

    Institute of Scientific and Technical Information of China (English)

    Zhong Jimao; Cheng Wanzheng

    2006-01-01

    In this paper, we researched the regional seismic status by using theories of the Damage Mechanics. The macroscopic damage status of the earth crust block, which is caused by earthquake fracture, is described with several concepts-the damage degree, the damage rate and the strain rate. In the earthquake process, the average strain rate of the studied block is equal to the sum of all seismic moment tensors of the earthquakes taking place in unit time and physical volume. To describe the anisotropy of microdamage of the crust block, we use the damage tensor that is expressed in the fissure density. By means of the transformation from the focal coordinate system to the observation system, we obtained the external normal vector of the focal fault plane expressed in its observation system and obtained the macrodamage degree of the researched block, which is calculated in dyadic. This provides a new analysis method for recognizing the underground damage status and the stress status.

  1. Technology status: Batteries and fuel cells

    Science.gov (United States)

    Fordyce, J. S.

    1978-01-01

    The current status of research and development programs on batteries and fuel cells and the technology goals being pursued are discussed. Emphasis is placed upon those technologies relevant to earth orbital electric energy storage applications.

  2. The Compact Pulsed Hadron Source Construction Status

    CERN Document Server

    Wei, Jie; Cai, Jinchi; Chen, Huaibi; Cheng, Cheng; Du, Qiang; Du, Taibin; Feng, Qixi; Feng, Zhe; Gong, Hui; Guan, Xialing; Han, Xiaoxue; Huang, Tuchen; Huang, Zhifeng; Li, Renkai; Li, Wenqian; Loong, Chun-Keung; Tang, Chuanxiang; Tian, Yang; Wang, Xuewu; Xie, Xiaofeng; Xing, Qingzi; Xiong, Zhengfeng; Xu, Dong; Yang, Yigang; Zeng, Zhi; Zhang, Huayi; Zhang, Xiaozhang; Zheng, Shu-xin; Zheng, Zhihong; Zhong, Bin; Billen, James; Young, Lloyd; Fu, Shinian; Tao, Juzhou; Zhao, Yaliang; Guan, Weiqiang; He, Yu; Li, Guohua; Li, Jian; Zhang, Dong-sheng; Li, Jinghai; Liang, Tianjiao; Liu, Zhanwen; Sun, Liangting; Zhao, Hongwei; Shao, Beibei; Stovall, James

    2010-01-01

    This paper reports the design and construction status, technical challenges, and future perspectives of the proton-linac based Compact Pulsed Hadron Source (CPHS) at the Tsinghua University, Beijing, China

  3. Cluster-like headache aura status

    NARCIS (Netherlands)

    Langedijk, M; van der Naalt, J; Luijckx, GJ; De Keyser, J

    2005-01-01

    We describe a patient with successive attacks (40 to 90 minutes) of cluster-like headache associated with aphasia, and contralateral hemihypesthesia and hemiplegia. The condition can best be described as cluster-like headache aura status.

  4. Conferences in Context: Status, Communication, and Evaluation

    Science.gov (United States)

    Wagner, L. Wesley; Brinkerhoff, Merlin

    1975-01-01

    The relationship between managers and three variables are examined: time commitments of managers to staff conferences, status or rank of managers, and the quality of communicative exchange in conference settings. (Author/DEP)

  5. Status of the MAJORANA DEMONSTRATOR experiment

    Energy Technology Data Exchange (ETDEWEB)

    Martin, R. D.; Abgrall, N.; Aguayo, Estanislao; Avignone, F. T.; Barabash, Alexander S.; Bertrand, F.; Boswell, M.; Brudanin, V.; Busch, Matthew; Caldwell, A. S.; Chan, Yuen-Dat; Christofferson, Cabot-Ann; Combs, Dustin C.; Detwiler, Jason A.; Doe, P. J.; Efremenko, Yuri; Egorov, Viatcheslav; Ejiri, H.; Elliott, S.; Esterline, James H.; Fast, James E.; Finnerty, P.; Fraenkle, Florian; Galindo-Uribarri, A.; Giovanetti, G. K.; Goett, J.; Green, M.; Gruszko, J.; Guiseppe, Vincente; Gusev, K.; Hallin, A. L.; Hazama, R.; Hegai, A.; Henning, R.; Hoppe, Eric W.; Howard, Stanley; Howe, M. A.; Keeter, K.; Kidd, M. F.; Kochetov, Oleg; Konovalov, S.; Kouzes, Richard T.; LaFerriere, Brian D.; Leon, Jonathan D.; Leviner, L.; Loach, J. C.; MacMullin, J.; MacMullin, S.; Mertens, S.; Mizouni, Leila; Nomachi, Masaharu; Orrell, John L.; O' Shaughnessy, Mark D.; Overman, Nicole R.; Phillips, David; Poon, Alan; Pushkin, K.; Radford, D. C.; Rielage, Keith; Robertson, R. G. H.; Romero-Romero, E.; Ronquest, M. C.; Schubert, Alexis G.; Shanks, B.; Shima, T.; Shirchenko, M.; Snavely, Kyle J.; Snyder, N.; Soin, Aleksandr; Suriano, Anne-Marie; Thompson, J.; Timkin, V.; Tornow, W.; Varner, R. L.; Vasilyev, Sergey; Vetter, Kai; Vorren, Kris R.; White, Brandon R.; Wilkerson, J. F.; Xu, W.; Yakushev, E.; Young, A.; Yu, Chang-Hong; Yumatov, Vladimir

    2014-07-08

    The MAJORANA DEMONSTRATOR neutrinoless double beta-decay experiment is currently under construction at the Sanford Underground Research Facility in South Dakota, USA. An overview and status of the experiment are given.

  6. Capital Improvement Program (CIP) Project Status

    Data.gov (United States)

    Montgomery County of Maryland — This dataset includes pertinent information relating to a capital project’s status administered by the Department of Transportation and the Department of General...

  7. EOS Terra: Mission Status Constellation MOWG

    Science.gov (United States)

    Mantziaras, Dimitrios

    2016-01-01

    This EOS Terra Mission Status Constellation MOWG will discuss mission summary; spacecraft subsystems summary, recent and planned activities; inclination adjust maneuvers, conjunction history, propellant usage and lifetime estimate; and end of mission plan.

  8. Spacecraft Fire Experiment (Saffire) Development Status

    DEFF Research Database (Denmark)

    Ruff, Gary A.; Urban, David L.; Fernandez-Pello, A. Carlos

    2014-01-01

    modeling effort will complement the experimental effort. An international topical team is collaborating with the NASA team in the definition of experiment requirements and performing supporting analysis, experimentation and technology development. The status of the overall experiment are summarized...

  9. Status of and performance estimates for QCDOC

    CERN Document Server

    Boyle, P; Christ, N H; Cristian, C; Dong, Z; Gara, A; Joó, B; Jung, C; Kim, C; Levkova, L; Liao, X; Liu, G; Mawhinney, Robert D; Ohta, S; Petrov, K V; Wettig, T; Yamaguchi, A

    2002-01-01

    QCDOC is a supercomputer designed for high scalability at a low cost per node. We discuss the status of the project and provide performance estimates for large machines obtained from cycle accurate simulation of the QCDOC ASIC.

  10. The Current Status of Galaxy Formation

    CERN Document Server

    Silk, Joe

    2012-01-01

    Understanding galaxy formation is one of the most pressing issues in cosmology. We review the current status of galaxy formation from both an observational and a theoretical perspective, and summarise the prospects for future advances.

  11. Tester status report: October-December 1978

    Energy Technology Data Exchange (ETDEWEB)

    Draut, C.F.

    1979-02-09

    This report details the status of the testers which provide the testing support of timers, actuators, detonators, firing sets, transducers, isolators, and pyrospacers during the time period of October through December 1978.

  12. Tester status report: April-June 1979

    Energy Technology Data Exchange (ETDEWEB)

    Draut, C.F.

    1979-08-31

    This report details tester status and activities in support of testing of timers, actuators, detonators, firing sets, transducers, isolators, and pyrospacers for the period of April through June 1979.

  13. Prognostic Factors for Refractory Status Epilepticus

    Directory of Open Access Journals (Sweden)

    J. Gordon Millichap

    2013-03-01

    Full Text Available Researchers at the Mayo Clinic, Rochester, MN studied the outcome and identified prognostic factors for refractory status epilepticus (RSE in 54 adult patients, median age 52 years [range 18-93].

  14. [Current status of autism studies].

    Science.gov (United States)

    Kurita, H

    2001-01-01

    The current status of autism studies was reviewed based on English articles published during the 1990s. Although the concepts of autism and pervasive developmental disorders (PDD) are established, diagnostic criteria of PDDNOS or atypical autism, which is frequently difficult to differentiate from autism, need to be established. The prevalence of autism has been estimated as about 0.05% in the U.S and many European countries, while it was reported to be 0.1% or higher in Japan and some European countries, though the reasons for this difference are unclear. High-functioning (IQ > or = 70) autism may not be as rare a condition as previously thought and both its difference from and similarity to Asperger's syndrome, the highest functioning PDD subtype, need clarification. About 20 to 40% of children with autism lose meaningful words by the age of 2 years and display autistic symptoms thereafter. Such autism, called the setback type in Japan, has been demonstrated to have a poorer adolescent/adult outcome compared to autism without setback and its relationship with childhood disintegrative disorder, which displays a clearer regression after normal development for at least the first 2 years of life, needs to be addressed. The etiology of autism is now considered mostly genetic for reasons, such as the significantly higher concordance rate of autism in identical twin pairs (60-80%) than in fraternal twin pairs (0-10%) and an 3-5% incidence of autism among sibs of an autism proband, 30 to 100 times higher than that in the general population. The involvement of several genes is implicated to create susceptibility for autism, yet the responsible genes have not been identified. Although there is no medication to cure autism, some psychotropic drugs, such as antipsychotics and SSRIs, seem effective for behavior problems in autism patients. Psychosocial treatments are the main therapeutic approach to autism, though they are yet to be well systematized. It is important to

  15. Turkey in Cyprus: Changing the Status Quo

    Directory of Open Access Journals (Sweden)

    Azuolas Bagdonas

    2016-04-01

    Full Text Available With few prospects for the resolution of the Cyprus dispute, the costs of the status quo are rising for Turkey. This article argues that Turkey could regain initiative without sacrificing its national interests by withdrawing its military forces stationed on the island and organizing a referendum on the future of the TRNC. The removal of the military would terminate Turkey's status as an occupying power, while a referendum could add legitimacy to the TRNC and put pressure on Cyprus.

  16. Achieving professional status: Australian podiatrists' perceptions

    Directory of Open Access Journals (Sweden)

    Vernon Wesley

    2009-02-01

    Full Text Available Abstract Background This paper explores the notion of professional status from the perspective of a sample of Australian podiatrists; how it is experienced, what factors are felt to affect it, and how these are considered to influence professional standing within an evolving healthcare system. Underpinning sociological theory is deployed in order to inform and contextualise the study. Methods Data were drawn from a series of in-depth semi-structured interviews (n = 21 and focus groups (n = 9 with podiatrists from across four of Australia's eastern states (Queensland, New South Wales, Victoria and Australian Capital Territory, resulting in a total of 76 participants. Semi-structured interview schedules sought to explore podiatrist perspectives on a range of features related to professional status within podiatry in Australia. Results Central to the retention and enhancement of status was felt to be the development of specialist roles and the maintenance of control over key task domains. Key distinctions in private and public sector environments, and in rural and urban settings, were noted and found to reflect differing contexts for status development. Marketing was considered important to image enhancement, as was the cache attached to the status of the universities providing graduate education. Conclusion Perceived determinants of professional status broadly matched those identified in the wider sociological literature, most notably credentialism, client status, content and context of work (such as specialisation and an ideological basis for persuading audiences to acknowledge professional status. In an environment of demographic and workforce change, and the resultant policy demands for healthcare service re-design, enhanced opportunities for specialisation appear evident. Under the current model of professionalism, both role flexibility and uniqueness may prove important.

  17. Marginal selenium status in northern Tasmania.

    Science.gov (United States)

    Beckett, Jeffrey M; Ball, Madeleine J

    2011-09-01

    Se plays many important roles in humans. Marginal Se status has been associated with adverse health effects including an increased risk of chronic disease such as cancer. There are few Australian data, but the population of Tasmania, Australia, is potentially at risk of marginal Se status. A cross-sectional study of 498 men and women aged 25-84 years was undertaken to assess the Se status of the northern Tasmanian population. Se status was assessed using dietary estimates and measures of serum Se and glutathione peroxidase (GPx). Mean Se intakes were 77·4 (sd 31·3) and 65·1 (sd 23·7) μg/d for men and women, respectively; 27 % of the subjects consumed less than the Australian/New Zealand estimated average requirement. Mean serum Se concentration was 89·1 (sd 15·1) μg/l; 83 % of the study subjects had serum Se concentrations below 100 μg/l and 60 % had serum Se concentration below 90 μg/l, suggesting that Se status in many subjects was inadequate for maximal GPx activity. This was supported by the positive association between serum Se and serum GPx (P < 0·001), indicating that enzyme activity was limited by Se concentrations. The lowest mean serum Se concentrations were observed in the oldest age ranges; however, the prevalence of marginal Se status was similar across age ranges and did not appear to be influenced by sex or socio-economic status. The prevalence of marginal Se status was high in all sex and age subgroups, suggesting that the northern Tasmanian population could benefit from increasing Se intakes.

  18. ILDG Middleware Working Group Status Report

    Energy Technology Data Exchange (ETDEWEB)

    B. Joo; W. Watson

    2004-09-01

    We report on the status of the ILDG Middleware Working Group. The Middleware Working Group was formed with the aim of designing standard middleware to allow the interoperation of the data grids of ILDG member collaborations. Details of the working group are given. In this contribution we outline the role of middleware in the ILDG, present our proposed middleware architecture and discuss our current status and future work within the working group.

  19. Status of the apeNEXT project

    CERN Document Server

    Ammendola, R; Boucaud, P; Cabibbo, Nicola; Carlo, F D; De Pietri, R; Renzo, F D; Errico, W; Fucci, A; Guagnelli, M; Kaldass, H; Lonardo, A; De Luca, S; Micheli, J; Morénas, V; Pène, O; Petronzio, Roberto; Palombi, Filippo; Pleiter, D; Paschedag, N; Rapuano, F; De Riso, P; Salamon, A; Salina, G; Sartori, L; Schifano, F; Simma, H; Tripiccione, R; Vicini, P; Boucaud, Ph.; 10.1016/S0920-5632(03)01755-9

    2003-01-01

    We present the current status of the apeNEXT project. Aim of this project is the development of the next generation of APE machines which will provide multi-teraflop computing power. Like previous machines, apeNEXT is based on a custom designed processor, which is specifically optimized for simulating QCD. We discuss the machine design, report on benchmarks, and give an overview on the status of the software development.

  20. The apeNEXT project (Status report)

    CERN Document Server

    Bodin, F; Cabibbo, Nicola; Carlo, F D; De Luca, S; De Pietri, R; Kaldass, H; Lonardo, A; Micheli, J; Morénas, V; Paschedag, N; Pleiter, D; Pène, O; Rapuano, F; Renzo, F D; Sartori, L; Schifano, F; Simma, H; Tripiccione, R; Vicini, P; Boucaud, Ph.

    2003-01-01

    We present the current status of the apeNEXT project. Aim of this project is the development of the next generation of APE machines which will provide multi-teraflop computing power. Like previous machines, apeNEXT is based on a custom designed processor, which is specifically optimized for simulating QCD. We discuss the machine design, report on benchmarks, and give an overview on the status of the software development.

  1. Hypothermia for Neuroprotection in Convulsive Status Epilepticus.

    Science.gov (United States)

    Legriel, Stephane; Lemiale, Virginie; Schenck, Maleka; Chelly, Jonathan; Laurent, Virginie; Daviaud, Fabrice; Srairi, Mohamed; Hamdi, Aicha; Geri, Guillaume; Rossignol, Thomas; Hilly-Ginoux, Julia; Boisramé-Helms, Julie; Louart, Benjamin; Malissin, Isabelle; Mongardon, Nicolas; Planquette, Benjamin; Thirion, Marina; Merceron, Sybille; Canet, Emmanuel; Pico, Fernando; Tran-Dinh, Yves-Roger; Bedos, Jean-Pierre; Azoulay, Elie; Resche-Rigon, Matthieu; Cariou, Alain

    2016-12-22

    Background Convulsive status epilepticus often results in permanent neurologic impairment. We evaluated the effect of induced hypothermia on neurologic outcomes in patients with convulsive status epilepticus. Methods In a multicenter trial, we randomly assigned 270 critically ill patients with convulsive status epilepticus who were receiving mechanical ventilation to hypothermia (32 to 34°C for 24 hours) in addition to standard care or to standard care alone; 268 patients were included in the analysis. The primary outcome was a good functional outcome at 90 days, defined as a Glasgow Outcome Scale (GOS) score of 5 (range, 1 to 5, with 1 representing death and 5 representing no or minimal neurologic deficit). The main secondary outcomes were mortality at 90 days, progression to electroencephalographically (EEG) confirmed status epilepticus, refractory status epilepticus on day 1, "super-refractory" status epilepticus (resistant to general anesthesia), and functional sequelae on day 90. Results A GOS score of 5 occurred in 67 of 138 patients (49%) in the hypothermia group and in 56 of 130 (43%) in the control group (adjusted common odds ratio, 1.22; 95% confidence interval [CI], 0.75 to 1.99; P=0.43). The rate of progression to EEG-confirmed status epilepticus on the first day was lower in the hypothermia group than in the control group (11% vs. 22%; odds ratio, 0.40; 95% CI, 0.20 to 0.79; P=0.009), but there were no significant differences between groups in the other secondary outcomes. Adverse events were more frequent in the hypothermia group than in the control group. Conclusions In this trial, induced hypothermia added to standard care was not associated with significantly better 90-day outcomes than standard care alone in patients with convulsive status epilepticus. (Funded by the French Ministry of Health; HYBERNATUS ClinicalTrials.gov number, NCT01359332 .).

  2. HUBUNGAN ANTARA ANEMI DAN STATUS BESI DENGAN STATUS IMUNITAS PADA ANAK YANG MENDAPAT VAKSINASI CAMPAK

    OpenAIRE

    Susi Suwarti Suwardi; Ance Murdiana Dahro; Sri Martuti; Reviana Christiani; Muhilal Muhilal

    2012-01-01

    THE RELATIONSHIP BETWEEN ANEMIA AND IRON STATUS WITH IMMUNE STATUS OF CHILDREN VACCINATED WITH MEASLES VACCINE.Background: Anemia, especially caused by iron deficiency, is one of several health problems in Indonesian children below 5 years of age. That condition seems appear in young children whose food is lack of iron. When those children are going to be vaccinated, how will the result be?.Objective: We sought to determine the relationship between anemia and iron with immune status of childr...

  3. Optimized high-throughput microRNA expression profiling provides novel biomarker assessment of clinical prostate and breast cancer biopsies

    Directory of Open Access Journals (Sweden)

    Fedele Vita

    2006-06-01

    Full Text Available Abstract Background Recent studies indicate that microRNAs (miRNAs are mechanistically involved in the development of various human malignancies, suggesting that they represent a promising new class of cancer biomarkers. However, previously reported methods for measuring miRNA expression consume large amounts of tissue, prohibiting high-throughput miRNA profiling from typically small clinical samples such as excision or core needle biopsies of breast or prostate cancer. Here we describe a novel combination of linear amplification and labeling of miRNA for highly sensitive expression microarray profiling requiring only picogram quantities of purified microRNA. Results Comparison of microarray and qRT-PCR measured miRNA levels from two different prostate cancer cell lines showed concordance between the two platforms (Pearson correlation R2 = 0.81; and extension of the amplification, labeling and microarray platform was successfully demonstrated using clinical core and excision biopsy samples from breast and prostate cancer patients. Unsupervised clustering analysis of the prostate biopsy microarrays separated advanced and metastatic prostate cancers from pooled normal prostatic samples and from a non-malignant precursor lesion. Unsupervised clustering of the breast cancer microarrays significantly distinguished ErbB2-positive/ER-negative, ErbB2-positive/ER-positive, and ErbB2-negative/ER-positive breast cancer phenotypes (Fisher exact test, p = 0.03; as well, supervised analysis of these microarray profiles identified distinct miRNA subsets distinguishing ErbB2-positive from ErbB2-negative and ER-positive from ER-negative breast cancers, independent of other clinically important parameters (patient age; tumor size, node status and proliferation index. Conclusion In sum, these findings demonstrate that optimized high-throughput microRNA expression profiling offers novel biomarker identification from typically small clinical samples such as breast

  4. Reciprocating Feed System Development Status

    Science.gov (United States)

    Trewek, Mary (Technical Monitor); Blackmon, James B.; Eddleman, David E.

    2005-01-01

    . Using this tool, a preliminary design of a representative crew exploration vehicle (CEV) has been considered. The design parameters selected for a representative system were modeled after the orbital maneuvering system (OMS) on the Shuttle Orbiter, with an increase of roughly a factor of ten in the delta- V capability and a greater thrust (30,000 lbs, vs. 12,000 lbs). Both storable and cryogenic propellants were considered. Results show that a RFS is a low mass alternative to conventional pressure fed systems, with a substantial increase in payload capability and that it is weight-competitive with turbopump systems at low engine pressure (a few hundred psi); at high engine pressures, the APTA RFS appears to offer the highest payload. We also present the status of the RFS test bed fabrication, assembly, and checkout. This test bed is designed to provide flow rates appropriate for engines in the roughly 10,000 to 30,000 lb thrust range.

  5. KONSUMSI AIR PUTIH, STATUS GIZI, DAN STATUS KESEHATAN PENGHUNI PANTI WERDA DI KABUPATEN PACITAN

    Directory of Open Access Journals (Sweden)

    Desy Dwi Aprillia

    2015-02-01

    Full Text Available ABSTRACTThe objective of this study was to learn and analyze the relationship between the consumption of plain water, nutritional status, and health status of panti werda residents in Pacitan. Design of this study was cross-sectional. Subject of this study were panti werda residents. As many as 24 people were chosen as subject. This result showed that 75% of subject had plain water sufficient levels were categorized as adequate and 25% were inadequate. Energy and protein sufficiency levels of subject were 33% and 42% categorized as normal. Micronutrient sufficient levels of subject consists of 83% phosphorus, 88% iron, and 100% vitamin A were categorized as adequate, but calcium and vitamin C sufficient levels as many as 96% and 100% were categorized as inadequate. As many as 42% subject had normal nutritional status, 25% were underweight, and 33% were overweight. Health status of subject as many as 54% were categorized as high and 46% were low. The Pearson and Spearman correlation test showed that nutritional status with nutrient intake, plain water consumption, and health status of subject had no significant relationship (p>0.05.Keywords: elderly, health status, nutrition intake, nutritional status, plain waterABSTRAKTujuan penelitian ini adalah menganalisis hubungan konsumsi air putih, status gizi, dan status kesehatan penghuni panti werda di Kabupaten Pacitan. Penelitian ini menggunakan desain cross-sectional pada 24 orang penghuni panti werda. Hasil studi menunjukkan bahwa 75% subjek memiliki tingkat kecukupan air putih yang tergolong kurang dan 25% tergolong cukup. Tingkat kecukupan energi dan protein subjek masing-masing sebesar 33% dan 42% tergolong normal. Tingkat kecukupan zat gizi mikro, yaitu 83% fosfor, 88% zat besi, dan 100% vitamin A termasuk dalam kategori cukup, namun tingkat kecukupan kalsium dan vitamin C, yaitu sebesar 96% dan 100% termasuk dalam kategori kurang. Sejumlah 42% subjek berstatus gizi normal, 25% gizi kurang, dan

  6. Adolescents' social status goals: relationships to social status insecurity, aggression, and prosocial behavior.

    Science.gov (United States)

    Li, Yan; Wright, Michelle F

    2014-01-01

    Peer status is an important aspect of adolescents' social lives and is pursued actively by them. Although extensive research has examined how social behaviors are related to peer status (e.g., social preference, popularity), little attention has been given to adolescents' social goals to obtain a desired peer status. Thus, this study examined two types of social status goals, popularity goal and social preference goal, and their relationships to social status insecurity and social behaviors among 405 ethnically diverse early adolescents (267 girls; M age = 12.92 years; age range = 11-15 years). After accounting for adolescents' attained peer statuses (popularity and social preference), both social status goals were related distinctly to aggressive and prosocial behaviors as measured by self reports and peer nominations. Specifically, higher endorsement of the popularity goal was related to more self-reported relational aggression, but less peer-nominated prosocial behavior. In contrast, higher endorsement of the social preference goal was linked to less self-reported overt and relational aggression, but more self-reported and peer-nominated prosocial behavior. In addition, this study reveals that adolescents' social status insecurity was related positively to both social status goals and had an indirect effect on adolescents' social behaviors through the mediation of popularity goal endorsement. There were variations in goal endorsement as shown by groups of adolescents endorsing different levels of each goal. The group comparison results on social behaviors were largely consistent with the correlational findings. This study provides new insights into adolescents' social cognitive processes about peer status and the implications of the two social status goals on adolescents' behavioral development.

  7. Status Inequalities in Business Exchange Relations in Luxury Markets

    NARCIS (Netherlands)

    M. Pocock (Miriam)

    2017-01-01

    markdownabstractIn this thesis we examine purchase exchanges between high status buyers and suppliers of lower status in luxury markets. While extant literature has treated status inequalities as an objective distinction in status rank, Study 1 on boat builders presents a novel approach towards conc

  8. 40 CFR 270.71 - Operation during interim status.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 26 2010-07-01 2010-07-01 false Operation during interim status. 270... (CONTINUED) EPA ADMINISTERED PERMIT PROGRAMS: THE HAZARDOUS WASTE PERMIT PROGRAM Interim Status § 270.71 Operation during interim status. (a) During the interim status period the facility shall not: (1)...

  9. 40 CFR 270.73 - Termination of interim status.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 26 2010-07-01 2010-07-01 false Termination of interim status. 270.73... (CONTINUED) EPA ADMINISTERED PERMIT PROGRAMS: THE HAZARDOUS WASTE PERMIT PROGRAM Interim Status § 270.73 Termination of interim status. Interim status terminates when: (a) Final administrative disposition of...

  10. 8 CFR 209.1 - Adjustment of status of refugees.

    Science.gov (United States)

    2010-01-01

    ... 8 Aliens and Nationality 1 2010-01-01 2010-01-01 false Adjustment of status of refugees. 209.1... STATUS OF REFUGEES AND ALIENS GRANTED ASYLUM § 209.1 Adjustment of status of refugees. The provisions of this section shall provide the sole and exclusive procedure for adjustment of status by a...

  11. GAMBARAN STATUS KESEHATAN PENDUDUK DI DAERAH PERBATASAN

    Directory of Open Access Journals (Sweden)

    Felly Philipus Senewe

    2016-09-01

    Full Text Available AbstractThe border region is a regional / geographic region associated with neighboring countries, withpeople living in this region united by ties of socio-economic and socio-cultural scope of a particularadministrative region after an agreement between states that border. Community health status can beknown of the status or disease morbidity, mortality or death status of the population or the nutritional statusof residents in the community. The health status of people living in border regions is expected to remainvery low when compared with other regions. Based on the data, Riskesdas 2007, data SUSENAS 2007, anddata Podes 2008, doing research to find out the picture of the health status of populations in border areas.This review is expected to be used by policy makers and the improvement of data base that affect the healthstatus of people residing in border areas. Total Samples 19 district border area. Sample population living inborder areas in 19 district : district Natuna, district Kupang, TTU, Belu, Sambas, Sanggau, Sintang, KapuasHulu, Bengkayang, Kutai Barat, Malinau, Nunukan, Kep. Talaud, North Halmahera, Jayapura, Merauke,Pegunungan Bintang, Boven Digoel and Keerom. Nutritional status of children of weight for age (27.1%,height for age (43.5% and weight for height (16.2% and this condition is still high compared with otherregions. Complete immunization coverage (44.2% and neonatal visits to health care workers (KN1: 40%and KN2: 23.5% were still low when compared with other regions. The scope of delivery by trained healthaides (48% is still very low when compared with other regions. Instead exclusive breastfeeding (45.1%better than other regions. Coverage of Ante Natal Care (Kl: 76.1% is quite high compared to otherregions. The prevalence of infectious diseases / communicable still high in the Border region from otherregions. The prevalence of non-communicable diseases including mental disorders in the areas mostDisadvantaged from other

  12. Relationship between haemophilia and social status.

    Science.gov (United States)

    Holstein, Katharina; Eifrig, Barbara; Langer, Florian

    2014-11-01

    The impact of haemophilia and its treatment on social status has not been well studied, although research into the quality of life of patients with haemophilia has shed some light on aspects of social and role functioning. Studies conducted before the advent of safe and effective coagulation factor replacement therapy suggest that the haemophilia population was predominantly of low socioeconomic status with many social disadvantages, including high rates of disability and unemployment and low rates of marriage. Since the availability of purified factor VIII concentrates that could be used in a home-care setting and as prophylaxis, most research suggests that social status and well-being amongst children, adolescents, and adults with haemophilia is not compromised, and is comparable to that of the general population. Children and adolescents with haemophilia do not generally feel disadvantaged, although haemophilia-related issues at school and amongst peer groups do arise. Recent studies in adults show higher than average rates of marriage and cohabitation and the attainment of a generally good educational status, but, as in the past, employment rates remain comparatively lower. Social status amongst the elderly with haemophilia who may have developed severe disability as a result of their condition is poorly defined and has never been formally studied. Additional research is recommended.

  13. The impact of smoking status on the health status of heart failure patients.

    LENUS (Irish Health Repository)

    Conard, Mark W

    2012-02-01

    Smoking is a major risk factor for the development of heart failure (HF). Yet, little is known about smoking\\'s effects on the health status of established HF patients. HF patients were recruited from outpatient clinics across North America. The Kansas City Cardiomyopathy Questionnaire (KCCQ) was used to assess disease-specific health status. Smoking behaviors were classified as never having smoked, prior smoker, and as having smoked within the past 30 days. Risk-adjusted multivariable regression was used to evaluate the association of smoking status with baseline and 1-year KCCQ overall summary scores. Smoking was not associated with baseline health status. However, a significant effect was observed on 1-year health status among outpatients with HF with current smokers reporting significantly lower KCCQ scores than never smokers or ex-smokers. These findings highlight an additional adverse consequence of smoking in HF patients not previously discussed.

  14. Service level status-a new real-time status display for IT services

    Energy Technology Data Exchange (ETDEWEB)

    Lopienski, S [IT Department, FIO group CERN, European Organization for Nuclear Research, 1211 Geneve 23 (Switzerland)], E-mail: Sebastian.Lopienski@cern.ch

    2008-07-15

    Nowadays, IT departments provide, and people use, computing services of an increasingly heterogeneous nature. There is thus a growing need for a status display that groups these different services and reports their status and availability in a uniform way. The Service Level Status (SLS) system addresses these needs by providing a web-based display that dynamically shows availability, basic information and statistics about various IT services, as well as the dependencies between them. This paper first introduces the requirements SLS had to meet, and the main concepts behind it, like service availability and status, Key Performance Indicators (KPIs), sub/meta-services, and service dependencies. It then describes the SLS system architecture, and some interesting implementation details, such as the usage of XML Schemas. Since clear visualization of service availability and status is one of the main goals of SLS, emphasis is put on describing the intuitive web-based user interface.

  15. When do low status individuals accept less? The interaction between self- and other-status during resource distribution

    Directory of Open Access Journals (Sweden)

    Philip Richard Blue

    2016-10-01

    Full Text Available In real-world social interactions, social status influences responses to resource distribution. However, the way in which one’s own social status interacts with another’s status to influence responses to resource distribution is far from clear. In the current study, we dynamically manipulated participants’ social status and then asked participants to act as recipients in the ultimatum game (UG along with proposers whose social status was made known to the participants. Experiment 1 used a between-participants design in which the participants were assigned as being of either high or low status according to their performance in a math competition (i.e., rank-inducing task. In Experiment 2, social status was manipulated within-subjects using the same rank-inducing task, with rounds of UG interleaved between rank-inducing sessions. Findings from the two experiments showed that both self-status and other-status influenced responses to UG offers, as participants were more likely to accept low offers from high status than low status proposers; this effect was particularly robust for low status participants when compared with high status participants. These findings suggest that, in comparison with individuals in high status, individuals in low status are more willing to accept low offers during resource distribution and are more affected by other-status considerations.

  16. Reconceptualizing retirement: A status-based approach.

    Science.gov (United States)

    Hershenson, David B

    2016-08-01

    The one thing on which essentially all retirement scholars agree is that there is no generally accepted definition of the term "retirement." Hence, it is not surprising that a plethora of competing models of the stages of retirement has been generated. To cut this Gordian knot, this paper proposes that the concept of statuses, which are not necessarily mutually exclusive or sequential, replace the idea of stages. Statuses better reflect observed human behavior and are more open to multicultural application, thus facilitating retirement research and clinical practice. The retirement statuses proposed here, which can exist in any combination or sequence, are retrenchment, exploration, try-out, involvement, reconsideration, and exiting (forming the acronym RETIRE).

  17. Nonconvulsive Status Epilepticus in Hepatic Encephalopathy

    Directory of Open Access Journals (Sweden)

    Hyung Kim

    2011-05-01

    Full Text Available We discuss a case of a 64-year-old male with a history of liver failure presenting with altered mental status, initially diagnosed with hepatic encephalopathy but ultimately diagnosed with nonconvulsive status epilepticus (NCSE by electroencephalogram (EEG. NCSE is a difficult diagnosis to make, given no clear consensus on diagnostic criteria. Especially in the intensive care unit setting of persistent altered mental status with no clear etiology, NCSE must be considered in the differential diagnosis, as the consequences of delayed diagnosis and treatment can be substantial. EEG can be useful in the evaluation of patients with hepatic encephalopathy who have persistently altered levels of consciousness despite optimal medical management. [West J Emerg Med. 2011;12(4:372–374.

  18. Altered mental status and endocrine diseases.

    Science.gov (United States)

    Park, Elizabeth; Abraham, Michael K

    2014-05-01

    Although the altered mental status is a common presentation in the emergency department, altered mental status caused by endocrine emergencies is rare. The altered patient could have an endocrine cause that can quickly improve with appropriate diagnosis and interventions. When dealing with limited information and an obtunded patient, it is important to have a broad differential diagnosis, pick up on the physical examination findings, and evaluate laboratory abnormalities that could suggest an underlying endocrine emergency. This article outlines the findings and provides a description of altered patients with endocrine emergencies to facilitate the diagnosis and treatment in the emergency department.

  19. Status of ISS Water Management and Recovery

    Science.gov (United States)

    Carter, Layne; Wilson, Laura Labuda; Orozco, Nicole

    2012-01-01

    Water management on ISS is responsible for the provision of water to the crew for drinking water, food preparation, and hygiene, to the Oxygen Generation System (OGS) for oxygen production via electrolysis, to the Waste & Hygiene Compartment (WHC) for flush water, and for experiments on ISS. This paper summarizes water management activities on the ISS US Segment, and provides a status of the performance and issues related to the operation of the Water Processor Assembly (WPA) and Urine Processor Assembly (UPA). This paper summarizes the on-orbit status as of May 2011, and describes the technical challenges encountered and lessons learned over the past year.

  20. Vitamin K status in chronic kidney disease.

    Science.gov (United States)

    McCabe, Kristin M; Adams, Michael A; Holden, Rachel M

    2013-11-07

    The purpose of this review is to summarize the research to date on vitamin K status in chronic kidney disease (CKD). This review includes a summary of the data available on vitamin K status in patients across the spectrum of CKD as well as the link between vitamin K deficiency in CKD and bone dynamics, including mineralization and demineralization, as well as ectopic mineralization. It also describes two current clinical trials that are underway evaluating vitamin K treatment in CKD patients. These data may inform future clinical practice in this population.

  1. Neutrino oscillations: Present status and outlook

    Indian Academy of Sciences (India)

    Thomas Schwetz

    2009-01-01

    The status of neutrino oscillations from global data is summarized, with the focus on the three-flavour picture. The status of sterile neutrino oscillation interpretations of the LSND anomaly in the light of recent MiniBooNE results is also discussed. Further-more, an outlook on the measurement of the mixing angle 13 in the near term future, as well as prospects to discover CP violation in neutrino oscillations and to determine the type of the neutrino mass ordering by long-baseline experiments in the long term future are given.

  2. Status of ISS Water Management and Recovery

    Science.gov (United States)

    Carter, Layne; Pruitt, Jennifer; Brown, Christopher A.; Bazley, Jesse; Gazda, Daniel; Schaezler, Ryan; Bankers, Lyndsey

    2016-01-01

    Water management on ISS is responsible for the provision of water to the crew for drinking water, food preparation, and hygiene, to the Oxygen Generation System (OGS) for oxygen production via electrolysis, to the Waste & Hygiene Compartment (WHC) for flush water, and for experiments on ISS. This paper summarizes water management activities on the ISS US Segment and provides a status of the performance and issues related to the operation of the Water Processor Assembly (WPA) and Urine Processor Assembly (UPA). This paper summarizes the on-orbit status as of May 2016 and describes the technical challenges encountered and lessons learned over the past year.

  3. Enterprise Accountants, Managerial Status And Gender Salaries

    Directory of Open Access Journals (Sweden)

    Bruce M. Bird

    2011-07-01

    Full Text Available This paper reports on the relationship between salary and a set of explanatory variables for a sample of enterprise (management accountants. In order to conduct the analysis, a sample was drawn from a large southeastern chapter of the Institute of Management Accountants (IMA. Based upon human capital theory and gender research, different groups of variables are regressed against salary for the 1 sample as a whole; 2 for those enterprise accountants with management status; and 3 for those enterprise accountants without managerial status. Each of the three hypotheses is partially supported. In addition, gender discrimination appears to be limited to non-managers.

  4. Neutrino mass and mixing – status

    Indian Academy of Sciences (India)

    Thomas Schwetz

    2012-11-01

    The status of neutrino oscillations from global data are summarized. An update on the three-flavour picture and recent developments are discussed with regard to the measurement of the mixing angle 13. Global data currently provide an indication at 3 that 13 is non-zero. Furthermore, the status of sterile neutrino oscillation interpretations of the LSND anomaly in the light of MiniBooNE results and a recent re-evaluation of the neutrino fluxes from nuclear reactors are discussed. Despite several hints for sterile neutrinos at the eV scale, there is severe tension in the global data and no consistent description of all data is possible.

  5. Correlation of sense of coherence with oral health behaviors, socioeconomic status, and periodontal status

    Directory of Open Access Journals (Sweden)

    Kommuri Sahithi Reddy

    2016-01-01

    Full Text Available Introduction: The sense of coherence (SOC has been suggested to be highly applicable concept in the public health area because a strong SOC is stated to decrease the likelihood of perceiving the social environment as stressful. This reduces the susceptibility to the health-damaging effect of chronic stress by lowering the likelihood of repeated negative emotions to stress perception. Materials and Methods: The demographic data and general information of subjects' oral health behaviors such as frequency of cleaning teeth, aids used to clean teeth, and dental attendance were recorded in the self-administered questionnaire. The SOC-related data were obtained using the short version of Antonovsky's SOC scale. The periodontal status was recorded based on the modified World Health Organization 1997 pro forma. Results: The total of 780 respondents comprising 269 (34.5% males and 511 (65.5% females participated in the study. A significant difference was noted among the subjects for socioeconomic status based on gender (P = 0.000. The healthy periodontal status (community periodontal index [CPI] code 0 was observed for 67 (24.9% males and 118 (23.1% females. The overall SOC showed statistically negative correlation with socioeconomic status scale (r = −0.287. The CPI and loss of attachment (periodontal status were significantly and negatively correlated with SOC. Conclusion: The present study concluded that a high level of SOC was associated with good oral health behaviors, periodontal status, and socioeconomic status.

  6. Magnesium deficiency: What is our status

    Science.gov (United States)

    Low magnesium intake has been implicated in a broad range of cardiometabolic conditions, including diabetes, hypertension, and cardiovascular disease. Dietary magnesium and total body magnesium status have a widely-used but imperfect biomarker in serum magnesium. Despite serum magnesium’s limitation...

  7. Status of the T2K experiment

    Science.gov (United States)

    Poutissou, J.-M.

    2011-07-01

    These lectures present the status of the Tokai to Kamioka Experiment (T2K) which just started taking data in early 2010. The goals and methodology for the experiment are presented as well as the challenges and prospects for determining the neutrino mixing parameters leading to neutrino oscillation with a particular attention to the determination of the mixing angle θ13.

  8. 9 CFR 166.15 - State status.

    Science.gov (United States)

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false State status. 166.15 Section 166.15 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE SWINE..., Texas, Utah, Vermont, Washington, West Virginia, and Wyoming. (c) The following States have...

  9. The Status of Research in Children's Television.

    Science.gov (United States)

    Searcy, Ellen; Chapman, Judith E.

    The intent of this document has been to provide a synthesis of the status of research on children's television that could be used as an information base for planning purposes. An outline or hierarchy of critical television research topics which need further investigation has been compiled from an analysis of major reference documents and personal…

  10. 40 CFR 52.2522 - Approval status.

    Science.gov (United States)

    2010-07-01

    ... provisions do not meet the requirements of 40 CFR 51.160 for scope. EPA also disapproves 45 CSR 13 section 9... 40 Protection of Environment 4 2010-07-01 2010-07-01 false Approval status. 52.2522 Section 52.2522 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS...

  11. 40 CFR 52.1323 - Approval status.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 4 2010-07-01 2010-07-01 false Approval status. 52.1323 Section 52.1323 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED... on January 16, 1979 (44 FR 3274) are met. (b) The Administrator approves Rule 10 CSR 10-2.290...

  12. Socioeconomic Status, Family Processes, and Individual Development

    Science.gov (United States)

    Conger, Rand D.; Conger, Katherine J.; Martin, Monica J.

    2010-01-01

    Research during the past decade shows that social class or socioeconomic status (SES) is related to satisfaction and stability in romantic unions, the quality of parent-child relationships, and a range of developmental outcomes for adults and children. This review focuses on evidence regarding potential mechanisms proposed to account for these…

  13. Disabled Youth: The Right to Adult Status.

    Science.gov (United States)

    Kelley-Laine, Kathleen

    The concept of "adult status" for young people with disabilities is explored in terms of its social, psychological, legal, and policy implications. The report argues that traditionally institutionalized rehabilitation techniques, whether in education, vocational training, or sheltered employment, have tended not to encourage autonomy and…

  14. Cognitive Status and Change among Iowa Centenarians

    Science.gov (United States)

    Margrett, Jennifer A.; Hsieh, Wen-Hua; Heinz, Melinda; Martin, Peter

    2012-01-01

    Equivocal evidence exists regarding the degree of cognitive stability and prevalence of cognitive impairment in very late life. The objective of the current study was to examine mental status performance and change over time within a sample of Iowa centenarians. The baseline sample consisted of 152 community-dwelling and institutionalized…

  15. Perceptions of Faculty Status among Academic Librarians

    Science.gov (United States)

    Galbraith, Quinn; Garrison, Melissa; Hales, Whitney

    2016-01-01

    This study measures the opinions of ARL librarians concerning the benefits and disadvantages of faculty status in academic librarianship. Average responses from faculty and nonfaculty librarians, as well as from tenured and tenure-track librarians, are analyzed to determine the general perceptions of each group. Overall, faculty librarians…

  16. What Punishment Does Falsifying Exam Status Merit?

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    Three years ago, He Daye, a middle-ranking official in southwest China’s Chongqing Municipality, changed his son’s ethnic status from the majority Han to the Tujia minority, in hopes that his son could get extra marks on

  17. The IFUSP microtron: status and perspectives

    Energy Technology Data Exchange (ETDEWEB)

    Martins, M.N.; Takahashi, J.; Malafronte, A.A.; Rios, P.B.; Lopes, M.L.; Bonini, A.L.; Lima, R.R. [Sao Paulo Univ., SP (Brazil). Inst. de Fisica. Lab. do Acelerador Nuclear

    2004-09-15

    In this paper we summarize the status of the racetrack microtron that is under construction at IFUSP, showing the achievements obtained in the transport, RF, control and vacuum systems. A description of the experimental equipment that will be available to the users is also presented. (author)

  18. Status of Research in Biomedical Engineering 1968.

    Science.gov (United States)

    National Inst. of General Medical Sciences (NIH), Bethesda, MD.

    This status report is divided into eight sections. The first four represent the classical engineering or building aspects of bioengineering and deal with biomedical instrumentation, prosthetics, man-machine systems and computer and information systems. The next three sections are related to the scientific, intellectual and academic influence of…

  19. Nutrition Status of HIV+ Children in Botswana

    Science.gov (United States)

    Nnyepi, Maria; Bennink, Maurice R.; Jackson-Malete, Jose; Venkatesh, Sumathi; Malete, Leapetswe; Mokgatlhe, Lucky; Lyoka, Philemon; Anabwani, Gabriel M.; Makhanda, Jerry; Weatherspoon, Lorraine J.

    2015-01-01

    Purpose: Identifying and addressing poor nutritional status in school-aged children is often not prioritized relative to HIV/AIDS treatment. The purpose of this paper is to elucidate the benefits of integrating nutrition (assessment and culturally acceptable food supplement intervention) in the treatment strategy for this target group.…

  20. Risk of Status Epilepticus in Epilepsy

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2004-10-01

    Full Text Available The occurrence of status epilepticus (SE after the initial diagnosis of epilepsy was determined in a prospective community-based cohort study of 613 children at Montefiore Medical Center, Bronx, NY; Yale Medical School, New Haven, CT; and BIOS/NIU, DeKalb, IL.

  1. Inferring Taxi Status Using GPS Trajectories

    CERN Document Server

    Zhu, Yin; Zhang, Liuhang; Santani, Darshan; Xie, Xing; Yang, Qiang

    2012-01-01

    In this paper, we infer the statuses of a taxi, consisting of occupied, non-occupied and parked, in terms of its GPS trajectory. The status information can enable urban computing for improving a city's transportation systems and land use planning. In our solution, we first identify and extract a set of effective features incorporating the knowledge of a single trajectory, historical trajectories and geographic data like road network. Second, a parking status detection algorithm is devised to find parking places (from a given trajectory), dividing a trajectory into segments (i.e., sub-trajectories). Third, we propose a two-phase inference model to learn the status (occupied or non-occupied) of each point from a taxi segment. This model first uses the identified features to train a local probabilistic classifier and then carries out a Hidden Semi-Markov Model (HSMM) for globally considering long term travel patterns. We evaluated our method with a large-scale real-world trajectory dataset generated by 600 taxis...

  2. On the Status of Critical Theory.

    Science.gov (United States)

    Nielsen, Kai

    1992-01-01

    Describes the nature and distinctiveness of critical theory and discusses it according to the viewpoints of Raymond Geuss and Jurgen Habermas. The logical status of a Habermasian critical theory is examined, defended from some traditional criticisms, and contrasted with both historical versions of critical theory and purely scientific theories.…

  3. Emotions and White Racial Identity Status Attitudes

    Science.gov (United States)

    Siegel, Matthew P.; Carter, Robert T.

    2014-01-01

    Relationships between emotional states and White racial identity status attitudes (Helms, 1984, 1990) were tested on a sample of 286 White students. The stimulus was a vignette in which one condition involved explicit racial information and one did not. Participants rated baseline and posttest emotions and completed the White Racial Identity…

  4. Chewing ability and dental functional status

    NARCIS (Netherlands)

    Nguyen, T.C.; Witter, D.J.; Bronkhorst, E.M.; Gerritsen, A.E.; Creugers, N.H.J.

    2011-01-01

    PURPOSE: The aim of this research was to explore the relationship between chewing ability and dental functional status, perceived oral health-related quality of life, and a number of background variables in a Vietnamese population. MATERIALS AND METHODS: The cluster stratified sample consisted of 2,

  5. Introduction: The moral status of technical artefacts

    NARCIS (Netherlands)

    Kroes, Peter; Verbeek, Peter-Paul; Kroes, Peter; Verbeek, Peter-Paul

    2014-01-01

    In recent decades, discussions about the question of how to morally assess technology and its influence on human beings have taken a new, intriguing twist. Issues about the moral status of technology -in the sense of whether technology itself or its influence on human life may be evaluated as morall

  6. Adventure Therapy: Current Status and Future Directions.

    Science.gov (United States)

    Berman, Dene

    1995-01-01

    Overviews articles in this issue that focus on the current status of adventure therapy and describe efforts aimed at defining a framework for conceptualizing adventure therapy. Notes changes in the field, including introduction of state laws requiring licensure of programs, the drive for program accreditation, and growing training opportunities in…

  7. Reactor antineutrino fluxes - status and challenges

    CERN Document Server

    Huber, Patrick

    2016-01-01

    In this contribution we describe the current understanding of reactor antineutrino fluxes and point out some recent developments. This is not intended to be a complete review of this vast topic but merely a selection of observations and remarks, which despite their incompleteness, will highlight the status and the challenges of this field.

  8. Reactor antineutrino fluxes – Status and challenges

    Energy Technology Data Exchange (ETDEWEB)

    Huber, Patrick, E-mail: pahuber@vt.edu

    2016-07-15

    In this contribution we describe the current understanding of reactor antineutrino fluxes and point out some recent developments. This is not intended to be a complete review of this vast topic but merely a selection of observations and remarks, which despite their incompleteness, will highlight the status and the challenges of this field.

  9. Appraisal, coping, health status, and psychological symptoms.

    Science.gov (United States)

    Folkman, S; Lazarus, R S; Gruen, R J; DeLongis, A

    1986-03-01

    In this study we examined the relation between personality factors (mastery and interpersonal trust), primary appraisal (the stakes a person has in a stressful encounter), secondary appraisal (options for coping), eight forms of problem- and emotion-focused coping, and somatic health status and psychological symptoms in a sample of 150 community-residing adults. Appraisal and coping processes should be characterized by a moderate degree of stability across stressful encounters for them to have an effect on somatic health status and psychological symptoms. These processes were assessed in five different stressful situations that subjects experienced in their day-to-day lives. Certain processes (e.g., secondary appraisal) were highly variable, whereas others (e.g., emotion-focused forms of coping) were moderately stable. We entered mastery and interpersonal trust, and primary appraisal and coping variables (aggregated over five occasions), into regression analyses of somatic health status and psychological symptoms. The variables did not explain a significant amount of the variance in somatic health status, but they did explain a significant amount of the variance in psychological symptoms. The pattern of relations indicated that certain variables were positively associated and others negatively associated with symptoms.

  10. Life Span Personality Stability in Sibling Statuses.

    Science.gov (United States)

    Rosenberg, B. G.

    Personality stability and change in sibling status in the one- and two-child-family are examined in this Study. Q-sort data were analyzed for the same 33 male and 34 female subjects during four periods of their lives-- early and late adolescence and early and middle adulthood. Results indicate that stability of personality was greatest during…

  11. Instructional Computing in Wyoming: Status and Recommendations.

    Science.gov (United States)

    Kansky, Bob

    The status of instructional computing in Wyoming's public schols as of April 1980 is reported. Specifically the document indicates the nature and extent of computer usage in grades K-12, summarizes teachers' opinions regarding the potential instructional uses of computers in the schools, and presents the recommendations of a select committee of…

  12. Cancer survival disparities by health insurance status.

    Science.gov (United States)

    Niu, Xiaoling; Roche, Lisa M; Pawlish, Karen S; Henry, Kevin A

    2013-06-01

    Previous studies found that uninsured and Medicaid insured cancer patients have poorer outcomes than cancer patients with private insurance. We examined the association between health insurance status and survival of New Jersey patients 18-64 diagnosed with seven common cancers during 1999-2004. Hazard ratios (HRs) with 95% confidence intervals for 5-year cause-specific survival were calculated from Cox proportional hazards regression models; health insurance status was the primary predictor with adjustment for other significant factors in univariate chi-square or Kaplan-Meier survival log-rank tests. Two diagnosis periods by health insurance status were compared using Kaplan-Meier survival log-rank tests. For breast, colorectal, lung, non-Hodgkin lymphoma (NHL), and prostate cancer, uninsured and Medicaid insured patients had significantly higher risks of death than privately insured patients. For bladder cancer, uninsured patients had a significantly higher risk of death than privately insured patients. Survival improved between the two diagnosis periods for privately insured patients with breast, colorectal, or lung cancer and NHL, for Medicaid insured patients with NHL, and not at all for uninsured patients. Survival from cancer appears to be related to a complex set of demographic and clinical factors of which insurance status is a part. While ensuring that everyone has adequate health insurance is an important step, additional measures must be taken to address cancer survival disparities.

  13. Iron status markers in 224 indigenous Greenlanders

    DEFF Research Database (Denmark)

    Milman, N; Byg, K E; Mulvad, G

    2001-01-01

    OBJECTIVE: To evaluate iron status in indigenous Greenlanders and its relationship to gender, age and intake of traditional Greenlandic foods. Methods: Serum ferritin, serum transferrin saturation and haemoglobin were evaluated in a population survey in 1993-1994 comprising 224 Greenlandic...

  14. Status of the AFP Project in ATLAS

    CERN Document Server

    AUTHOR|(INSPIRE)INSPIRE-00224260; The ATLAS collaboration

    2017-01-01

    Status of the AFP project in the ATLAS experiment is given. In 2016 one arm of the AFP detector was installed and first data have been taken. In parallel with integration of the AFP subdetector into the ATLAS TDAQ nad DCS, beam tests and preparations for the installation of the 2nd arm are performed.

  15. Schedule and status of irradiation experiments

    Energy Technology Data Exchange (ETDEWEB)

    Rowcliffe, A.F.; Grossbeck, M.L.; Robertson, J.P. [Oak Ridge National Lab., TN (United States)

    1998-03-01

    The current status of reactor irradiation experiments is presented in tables summarizing the experimental objectives, conditions, and schedule. Currently, the program has four irradiation experiments in reactor, and five experiments in the design or construction stages. Postirradiation examination and testing is in progress on ten experiments.

  16. Status and recent highlights from CMS

    CERN Document Server

    Van Mulders, Petra Karel Ann

    2016-01-01

    The LHC Run-2 at a center of mass energy of 13 TeV started in 2015. This proceeding highlights some of the physics results based on the collision data collected by the CMS experiment in 2015. In addition, the status and readiness of the experiment for the collisions in 2016 are discussed with concrete examples on the object reconstruction performance.

  17. Between Status and Solidarity in Singapore

    Science.gov (United States)

    Cavallaro, Francesco; Chin, Ng Bee

    2009-01-01

    Language attitude studies have shown that the majority language and its speakers tend to be rated positively along status, intelligence, and power dimensions ("Educated", "Successful", "Intelligent"), while the minority variety and its speakers elicit positive responses in the solidarity semantic category…

  18. When does anticipating group-based shame lead to lower ingroup favoritism? The role of status and status stability : The role of status and status stability

    NARCIS (Netherlands)

    Shepherd, L.; Spears, Russell; Manstead, A.S.R.

    2013-01-01

    In two studies we examined whether and when anticipated group-based shame leads to less ingroup favoritism on the part of members of high-status groups in stable hierarchies. In Study 1 (n = 195) we measured anticipated group-based shame and found that it only negatively predicted ingroup favoritism

  19. Social Status Profiles among First Grade Children

    Science.gov (United States)

    Acquah, Emmanuel O.; Palonen, Tuire; Lehtinen, Erno; Laine, Kaarina

    2014-01-01

    The focus of our study is social status among first graders. In particular, we will consider the relationship between acceptance and rejection, and how these are connected to three social behavioral traits: bullying, victimization, and social withdrawal. The data set is from peer nominations of 748 children from 49 classrooms in the southwest of…

  20. Assessing conservation status of Peninsular Malaysian Begonias

    NARCIS (Netherlands)

    Chua, L.S.L.; Kiew, R.; Chan, Y.M.

    2009-01-01

    Following the revision of Peninsular Malaysian Begonia, a project that involved extensive fieldwork, we now have sufficient data to assess their conservation status. Out of 54 taxa, 48 are endemic to Peninsular Malaysia. No fewer than 30 taxa are known from fewer than five localities; 24 taxa are Cr

  1. Cardiac Vagal Regulation and Early Peer Status

    Science.gov (United States)

    Graziano, Paulo A.; Keane, Susan P.; Calkins, Susan D.

    2007-01-01

    A sample of 341 5 1/2-year-old children participating in an ongoing longitudinal study was the focus of a study on the relation between cardiac vagal regulation and peer status. To assess cardiac vagal regulation, resting measures of respiratory sinus arrhythmia (RSA) and RSA change (suppression) to 3 cognitively and emotionally challenging tasks…

  2. Laboratory Indices of Nutritional Status in Pregnancy.

    Science.gov (United States)

    National Academy of Sciences-National Research Council, Washington, DC. Food and Nutrition Board.

    This report reviews the current state of knowledge regarding laboratory indices of nutritional and metabolic status during normal pregnancy in order to provide normative data with respect to such indices in healthy pregnant women. The report contains seven chapters: Physiologic Adjustments in General; Hematologic Indices; Electrolytes in Normal…

  3. Status of Women in Social Work Education

    Science.gov (United States)

    Sakamoto, Izumi; Anastas, Jeane W.; McPhail, Beverly M.; Colarossi, Lisa G.

    2008-01-01

    This invited study sought to determine the current status of women in social work education for the special section of the "Journal of Social Work Education." Analysis of the latest data available indicate that gender differences remain pervasive across many aspects of social work education, including pay, rank, job duties, and tenure.…

  4. Schedule and status of irradiation experiments

    Energy Technology Data Exchange (ETDEWEB)

    Rowcliffe, A.F.; Grossbeck, M.L.; Robertson, J.P. [Oak Ridge National Lab., TN (United States)

    1998-09-01

    The current status of reactor irradiation experiments is presented in tables summarizing the experimental objectives, conditions, and schedule. Currently, the program has one irradiation experiment in reactor and five experiments in the design or construction stages. Postirradiation examination and testing is in progress on ten experiments.

  5. Overseas Contingency Operations Funding: Background and Status

    Science.gov (United States)

    2016-06-13

    Research Service 52 Item Definition of Criteria Operations Direct War costs:  transport of personnel, equipment, and supplies to, from, and...Background and Status Congressional Research Service 53 Item Definition of Criteria Industrial Base Capacity Programs to maintain industrial base

  6. Status Report on the Antiproton Decelerator (AD)

    CERN Document Server

    Erikson, T; Möhl, D

    2001-01-01

    CERN's new Antiproton Decelerator (AD) has been delivering a 100 MeV/c antiproton beam to three experiments (ASACUSA, AHENA and ATRAP) since July 10th, 2000. In this status report, we summarise the initial performance of the AD, draw provisional conclusions from the first month of operation and finally give some prospects for the future.

  7. Species status of Mill Creek Elliptio

    Energy Technology Data Exchange (ETDEWEB)

    Davis, G.M. [Academy of Natural Sciences (United States); Mulvey, M. [Savannah River Ecology Lab., Aiken, SC (United States)

    1993-12-31

    This report discusses environmental effects of the Savannah River Plant on aqautic populations in Mill Creek and surrounding tributaries. Of particular concern was the status of Elliptio. Genetics and phenotypic characteristics have shown that the current classification system is not adequate for these populations. The appendices characterize genetic variability at different loci, electrophoretic data, allele frequencies, sympatric species, and anatomical characters.

  8. Child and adolescent psychiatry and family status

    DEFF Research Database (Denmark)

    Esbjørn, Barbara Hoff; Levin, Eline; Høyer, Mette;

    2008-01-01

    BACKGROUND: Much attention has been given to parental separation as a possible risk factor for adverse child development; however, little information is available regarding the family status of children referred to psychiatric facilities. AIMS: To assess the association between psychiatric illnes...

  9. Academic Librarians: Status, Privileges, and Rights

    Science.gov (United States)

    Vix, Heidi M.; Buckman, Kathie M.

    2012-01-01

    Three surveys from the College and University Library Division (CULD) of the Arkansas Library Association (ArLA) from the past six years representing forty-four academic institutions were studied to determine the number of students per librarian on campus, salary, faculty status, contract-length, and maternity/paternity leave for librarians.…

  10. Assessing Family Economic Status From Teacher Reports.

    Science.gov (United States)

    Moskowitz, Joel M.; Hoepfner, Ralph

    The utility of employing teacher reports about characteristics of students and their parents to assess family economic status was investigated using multiple regression analyses. The accuracy of teacher reports about parents' educational background was also explored, in addition to the effect of replacing missing data with logical, mean, or modal…

  11. Status of Cases in the Supreme Court.

    Science.gov (United States)

    Chronicle of Higher Education, 1986

    1986-01-01

    The status as of October 9, 1986 of higher education-related Supreme Court litigation is outlined concerning: accreditation, affirmative action, asbestos, bar examinations, collective bargaining, creationism, racial discrimination, infectious disease, liquor sales, pensions, pregnancy benefits, revocation of degree, sexual harassment, and student…

  12. Laboratory assessment of vitamin B12 status.

    Science.gov (United States)

    Harrington, Dominic J

    2017-02-01

    The detection and correction of vitamin B12 (B12) deficiency prevents megaloblastic anaemia and potentially irreversible neuropathy and neuropsychiatric changes. B12 status is commonly estimated using the abundance of the vitamin in serum, with ∼148 pmol/L (200 ng/L) typically set as the threshold for diagnosing deficiency. Serum B12 assays measure the sum of haptocorrin-bound and transcobalamin-bound (known as holotranscobalamin) B12 It is only holotranscobalamin that is taken up by cells to meet metabolic demand. Although receiver operator characteristic curves show holotranscobalamin measurement to be a moderately more reliable marker of B12 status than serum B12, both assays have an indeterminate range. Biochemical evidence of metabolic abnormalities consistent with B12 insufficiency is frequently detected despite an apparently sufficient abundance of the vitamin. Laboratory B12 status markers that reflect cellular utilisation rather than abundance are available. Two forms of B12 act as coenzymes for two different reactions. Methionine synthase requires methylcobalamin for the remethylation of methionine from homocysteine. A homocysteine concentration >20 µmol/L may suggest B12 deficiency in folate-replete patients. In the second B12-dependent reaction, methylmalonyl-CoA mutase uses adenosylcobalamin to convert methylmalonyl-CoA to succinyl-CoA. In B12 deficiency excess methylmalonyl-CoA is hydrolysed to methylmalonic acid. A serum concentration >280 nmol/L may suggest suboptimal status in young patients with normal renal function. No single laboratory marker is suitable for the assessment of B12 status in all patients. Sequential assay selection algorithms or the combination of multiple markers into a single diagnostic indicator are both approaches that can be used to mitigate inherent limitations of each marker when used independently.

  13. Indigenous health and socioeconomic status in India.

    Directory of Open Access Journals (Sweden)

    S V Subramanian

    2006-10-01

    Full Text Available BACKGROUND: Systematic evidence on the patterns of health deprivation among indigenous peoples remains scant in developing countries. We investigate the inequalities in mortality and substance use between indigenous and non-indigenous, and within indigenous, groups in India, with an aim to establishing the relative contribution of socioeconomic status in generating health inequalities. METHODS AND FINDINGS: Cross-sectional population-based data were obtained from the 1998-1999 Indian National Family Health Survey. Mortality, smoking, chewing tobacco use, and alcohol use were four separate binary outcomes in our analysis. Indigenous status in the context of India was operationalized through the Indian government category of scheduled tribes, or Adivasis, which refers to people living in tribal communities characterized by distinctive social, cultural, historical, and geographical circumstances.Indigenous groups experience excess mortality compared to non-indigenous groups, even after adjusting for economic standard of living (odds ratio 1.22; 95% confidence interval 1.13-1.30. They are also more likely to smoke and (especially drink alcohol, but the prevalence of chewing tobacco is not substantially different between indigenous and non-indigenous groups. There are substantial health variations within indigenous groups, such that indigenous peoples in the bottom quintile of the indigenous-peoples-specific standard of living index have an odds ratio for mortality of 1.61 (95% confidence interval 1.33-1.95 compared to indigenous peoples in the top fifth of the wealth distribution. Smoking, drinking alcohol, and chewing tobacco also show graded associations with socioeconomic status within indigenous groups. CONCLUSIONS: Socioeconomic status differentials substantially account for the health inequalities between indigenous and non-indigenous groups in India. However, a strong socioeconomic gradient in health is also evident within indigenous

  14. Determinants of selenium status in healthy adults

    Directory of Open Access Journals (Sweden)

    Hoeg Antonia

    2011-07-01

    Full Text Available Abstract Background Selenium (Se status in non-deficient subjects is typically assessed by the Se contents of plasma/serum. That pool comprises two functional, specific selenoprotein components and at least one non-functional, non-specific components which respond differently to changes in Se intake. A more informative means of characterizing Se status in non-deficient individuals is needed. Methods Multiple biomarkers of Se status (plasma Se, serum selenoprotein P [SEPP1], plasma glutathione peroxidase activity [GPX3], buccal cell Se, urinary Se were evaluated in relation to selenoprotein genotypes (GPX1, GPX3, SEPP1, SEP15, dietary Se intake, and parameters of single-carbon metabolism in a cohort of healthy, non-Se-deficient men (n = 106 and women (n = 155. Conclusions Plasma Se concentration was 142.0 ± 23.5 ng/ml, with GPX3 and serum-derived SEPP1 calculated to comprise 20% and 34%, respectively, of that total. The balance, comprised of non-specific components, accounted for virtually all of the interindividual variation in total plasma Se. Buccal cell Se was associated with age and plasma homocysteine (hCys, but not plasma Se. SEPP1 showed a quadratic relationship with body mass index, peaking at BMI 25-30. Urinary Se was greater in women than men, and was associated with metabolic body weight (kg0.75, plasma folate, vitamin B12 and hCys (negatively. One GPX1 genotype (679T/T was associated with significantly lower plasma Se levels than other allelic variants. Selenium intake, estimated from food frequency questionnaires, did not predict Se status as indicated by any biomarker. These results show that genotype, methyl-group status and BMI contribute to variation in Se biomarkers in Se-adequate individuals.

  15. The Cost of Collaborating with Climbers of Status Hierarchies

    DEFF Research Database (Denmark)

    Jeppesen, Jacob; Vaarst Andersen, Kristina

    , but at times individuals or organizations successfully climb the status hierarchy or fall from grace. A growing body of research focuses on these status dynamics rather than static status measures. Based on data from 826 scientists affiliated with a Large Scale Research Facility (LSRF) collaborating on 1282 on......-site and 151,302 off-site publications we analyze relationships between status dynamics, tie formation and performance among scientists. We find that there is a cost of collaborating with rising stars – in the form of increasing status - as collaboration partners’ positive status shifts is negatively...

  16. Low social status decreases the neural salience of unfairness

    Directory of Open Access Journals (Sweden)

    Jie eHu

    2014-11-01

    Full Text Available Social hierarchy exists in almost all social species and affects everything from resource allocation to the development of intelligence. Previous studies showed that status within a social hierarchy influences the perceived fairness of income allocation. However, the effect of one’s social status on economic decisions is far from clear, as are the neural processes underlying these decisions. In this study, we dynamically manipulated participants’ social status and analyzed their behavior as recipients in the ultimatum game, during which event-related potentials (ERPs were recorded. Behavioral results showed that acceptance rates for offers increased with the fairness level of offers. Importantly, participants were less likely to accept unfair offers when they were endowed with high status than with low status. In addition, cues indicating low status elicited a more positive P2 than cues indicating high status in an earlier time window (170 – 240 ms, and cues indicating high status elicited a more negative N400 than did cues indicating low status in a later time window (350 – 520 ms. During the actual reception of offers, the late positivity potential (LPP, 400 – 700 ms for unfair offers was more positive in the high status condition than in the low status condition, suggesting a decreased arousal for unfair offers during low status. These findings suggest a strong role of social status in modulating individual behavioral and neural responses to fairness.

  17. Low social status decreases the neural salience of unfairness.

    Science.gov (United States)

    Hu, Jie; Cao, Yuan; Blue, Philip R; Zhou, Xiaolin

    2014-01-01

    Social hierarchy exists in almost all social species and affects everything from resource allocation to the development of intelligence. Previous studies showed that status within a social hierarchy influences the perceived fairness of income allocation. However, the effect of one's social status on economic decisions is far from clear, as are the neural processes underlying these decisions. In this study, we dynamically manipulated participants' social status and analyzed their behavior as recipients in the ultimatum game (UG), during which event-related potentials (ERPs) were recorded. Behavioral results showed that acceptance rates for offers increased with the fairness level of offers. Importantly, participants were less likely to accept unfair offers when they were endowed with high status than with low status. In addition, cues indicating low status elicited a more positive P2 than cues indicating high status in an earlier time window (170-240 ms), and cues indicating high status elicited a more negative N400 than cues indicating low status in a later time window (350-520 ms). During the actual reception of offers, the late positivity potential (LPP, 400-700 ms) for unfair offers was more positive in the high status condition than in the low status condition, suggesting a decreased arousal for unfair offers during low status. These findings suggest a strong role of social status in modulating individual behavioral and neural responses to fairness.

  18. Reflections on the Academic Status of Lexicography

    Directory of Open Access Journals (Sweden)

    Sven Tarp

    2011-10-01

    Full Text Available

    ABSTRACT: Two main camps have been formed with regard to the philosophical and academic status of lexicography: one considering lexicography an independent scientific discipline, and the other opposing such a scientific status. This article discusses some of the arguments from the second camp and argues that lexicography should be considered an independent scientific discipline. The argumentation is based on the fact that the subject field of lexicography is different from the subject fields of any other discipline, including linguistics. In this sense, the concept of a lexicographical work is broader than the more reduced concept of a dictionary. Lexicographical works, including dictionaries, are considered cultural artefacts and utility tools produced in order to meet punctual information needs detected in society. In this way, they have during the millenniums covered almost all spheres of human activity and knowledge. The theory and science of lexicography should not focus on the differences regarding the specific content of all these works, but on aspects that unite them and are common to all of them. In this regard, some of the core characteristics of lexicography as an independent discipline are discussed together with its complex relation to other disciplines. Lexicographical theory is understood as a systematic set of statements about its subject field. Finally, the article argues that the fact that this theory may seem too abstract and difficult to some working lexicographers does not in itself invalidate its independent scientific status, although a close relation between theory and practice is recommended.

    OPSOMMING: Gedagtes oor die akademiese status van die leksikografie. Twee hoofkampe het ontwikkel met betrekking tot die filosofiese en akademiese status van die leksikografie: een wat die leksikografie beskou as 'n onafhanklike wetenskaplike dissipline, en die ander wat so 'n wetenskaplike status teenstaan. Hierdie artikel

  19. Breast cancer receptor status assessment and clinicopathological association in Nigerian women: A retrospective analysis

    Directory of Open Access Journals (Sweden)

    Makanjuola SBL

    2014-08-01

    Full Text Available Background: Breast cancer markers are becoming increasingly important in breast cancer research due to their impact on prognosis, treatment and survival. The present retrospective study was carried out to quantify the proportion of estrogen (ER, progesterone (PR, and human epithelial receptor 2 (HER2 expressions and their association with tumour grade, age, and tumour size in breast cancer patients in Nigeria. Materials and methods: The paraffin embedded tissue sections were analysed for breast cancer markers using monoclonal antibody SP1 for ER and SP2 for PR and polyclonal antibody ErbB2 for HER2. Results: A total of 286 breast cancer paraffin wax tissue sections were analysed for ER, PR and HER2 expression. Of all the tissue samples examined, 20 (7% were ER-positive, 6 (2.1% were PR-positive, 11 (3.8% were HER2-positive whereas 248 (87% were triple-negative breast carcinoma. ER- and PR-positivity was associated with early grade I and II tumours (P 50mm (P < 0.0001. Conclusion: A small proportion of Nigerian women with breast cancer are ER/PR-positive which are associated with less aggressive, better prognosis and benefit from endocrine therapy. An even smaller proportion of patients with aggressive tumors were HER2-posivite but responsive to Herceptin treatment. Unfortunately, a very high proportion of cases were triple-negative which is associated with very aggressive tumours and no targeted treatment, which may explain the high mortality rates from breast cancer in Nigeria.

  20. Nutritional Status Assessment (SMO 016E)

    Science.gov (United States)

    Smith, S. M.; Zwart, S. R.; Heer, M.; Ericson, K.; Coburn, S. P.; Booth, S. A.; Jones, J. A.; Lupton, J.

    2009-01-01

    Until 2006, it was not been possible to assess nutritional status of crewmembers on the ISS during flight because blood and urine could not be collected during ISS missions. Postflight observations of alterations in status of several nutrients are troubling, and we require the ability to monitor the status of these nutrients during flight to determine if there is a specific impetus or timeframe for these changes. In addition to the monitoring of crew nutritional status during flight, in-flight sample collection would allow better assessment of countermeasure effectiveness. Collecting samples during flight is one of the objectives of SMO 016E, and it is also designed to expand the current medical requirement for nutritional assessment (MR016L) to include additional normative markers for assessing crew health and countermeasure effectiveness. Additional markers of bone metabolism will be measured to better monitor bone health and the effectiveness of countermeasures to prevent bone resorption. New markers of oxidative damage will be measured to better assess the type of oxidative insults that occur during space flight. The array of nutritional assessment variables will be expanded to include ones that will allow us to better understand changes in folate, vitamin K, and vitamin B6 status, as well as risk factors for cardiovascular and oxidative damage during and after flight. Stress hormones and hormones that affect bone and muscle metabolism will also be measured. Measuring these additional variables will allow us to better monitor the health of crewmembers and make more accurate recommendations for their rehabilitation. Several nutritional assessment variables are altered at landing, but it is not known how long these changes persist. We extended the original protocol to include an additional postflight blood and urine sample collection 30 days after landing. Data are being collected before, during, and after flight. These data will provide a complete survey of how

  1. Status and management of muskox on Nunivak Island, Alaska

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — This report is on the status and management of muskox on Nunivak Island, Alaska during 1970. An analysis of the status and management of muskox is summarized,...

  2. The nutritional status in adolescent Spanish cyclists

    Directory of Open Access Journals (Sweden)

    C. Julián-Almárcegui

    2013-08-01

    Full Text Available Introduction: Adolescence is an important period of nutritional vulnerability due to the increased dietary requirements. Objective: To describe the nutritional status of adolescent cyclist and a group of normoactive controls. Methods: The HELENA Dietary Assessment Tool was used to evaluate the nutritional intake of 20 adolescent cyclists and 17 controls. Total energy intake, resting energy expenditure (REE, total energy expenditure (TEE, macronutrients and several micronutrients were registered and compared with dietary guidelines. Results: REE was lower and TEE higher in cyclists than in controls (both P < 0.01. Significant differences were observed in phosphorus and vitamin B1 being higher in cyclists (P < 0.05. Most participants, both cyclist and controls, did not reach the diet requirements for macronutrients, vitamins and minerals. Conclusion: Nutritional status of adolescent cyclists and controls seems not to fulfil the requirements in quantity and quality. Possible implications for actual and future health especially in athlete adolescents need further research.

  3. Annual Hanford Site Environmental Permitting Status Report

    Energy Technology Data Exchange (ETDEWEB)

    HOMAN, N.A.

    2000-10-01

    The information contained in, and/or referenced in, this Annual Hanford Site Environmental Permitting Status Report addresses Permit Condition II.W (Other Permits and/or Approvals) of the Dangerous Waste Portion of the Resource Conservation and Recovery Act Permit for the Treatment, Storage, and Disposal of Dangerous Waste, issued by the Washington State Department of Ecology (WA7890008967). Condition II.W specifies that the Permittees are responsible for obtaining all other applicable federal, state, and local permits authorizing the development and operation of the Hanford Facility. This status report also addresses Permit Condition I.E.22, as interpreted in Section 12.1.25 of the Hanford Facility Dangerous Waste Permit Application, General Information Portion (DOE/RL-91-28, Rev. 4), that states this report will be prepared annually and a copy of this report will be placed in the Facility Operating Record, General Information file by October 1 of each year.

  4. Current status of the DARPA Quantum Network

    CERN Document Server

    Elliott, C; Pearson, D; Pikalo, O; Schlafer, J; Yeh, H; Elliott, Chip; Colvin, Alexander; Pearson, David; Pikalo, Oleksiy; Schlafer, John; Yeh, Henry

    2005-01-01

    This paper reports the current status of the DARPA Quantum Network, which became fully operational in BBN's laboratory in October 2003, and has been continuously running in 6 nodes operating through telecommunications fiber between Harvard University, Boston University, and BBN since June 2004. The DARPA Quantum Network is the world's first quantum cryptography network, and perhaps also the first QKD systems providing continuous operation across a metropolitan area. Four more nodes are now being added to bring the total to 10 QKD nodes. This network supports a variety of QKD technologies, including phase-modulated lasers through fiber, entanglement through fiber, and freespace QKD. We provide a basic introduction and rational for this network, discuss the February 2005 status of the various QKD hardware suites and software systems in the network, and describe our operational experience with the DARPA Quantum Network to date. We conclude with a discussion of our ongoing work.

  5. Status of the SPIRAL2 injector commissioning

    Science.gov (United States)

    Thuillier, T.; Angot, J.; Barué, C.; Bertrand, P.; Biarrotte, J. L.; Canet, C.; Denis, J.-F.; Ferdinand, R.; Flambard, J.-L.; Jacob, J.; Jardin, P.; Lamy, T.; Lemagnen, F.; Maunoury, L.; Osmond, B.; Peaucelle, C.; Roger, A.; Sole, P.; Touzery, R.; Tuske, O.; Uriot, D.

    2016-02-01

    The SPIRAL2 injector, installed in its tunnel, is currently under commissioning at GANIL, Caen, France. The injector is composed of two low energy beam transport lines: one is dedicated to the light ion beam production, the other to the heavy ions. The first light ion beam, created by a 2.45 GHz electron cyclotron resonance ion source, has been successfully produced in December 2014. The first beam of the PHOENIX V2 18 GHz heavy ion source was analyzed on 10 July 2015. A status of the SPIRAL2 injector commissioning is given. An upgrade of the heavy ion source, named PHOENIX V3 aimed to replace the V2, is presented. The new version features a doubled plasma chamber volume and the high charge state beam intensity is expected to increase by a factor of 1.5 to 2 up to the mass ˜50. A status of its assembly is proposed.

  6. Gabapentin withdrawal presenting as status epilepticus.

    Science.gov (United States)

    Barrueto, Fermin; Green, Jonah; Howland, Mary Ann; Hoffman, Robert S; Nelson, Lewis S

    2002-01-01

    A 34-year-old male with lumbar disc disease and surgery was placed on gabapentin daily for chronic back pain. He remained on a steady dose of 8000 mg/day for 9 months, almost doubled what is considered therapeutic. He ran out of medication, was unable to refill his prescription for 2 days and presented to the emergency department in status epilepticus. There was no previous history of seizure disorder and he was on no other medications. A medical evaluation for an alternative etiology of his seizures was negative. Although gabapentin withdrawal has been previously reported and usually consists of anxiety, diaphoresis, and palpitations, this is the first reported patient with generalized seizures and status epilepticus secondary to gabapentin withdrawal.

  7. Smart Grid Status and Metrics Report Appendices

    Energy Technology Data Exchange (ETDEWEB)

    Balducci, Patrick J. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Antonopoulos, Chrissi A. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Clements, Samuel L. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Gorrissen, Willy J. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Kirkham, Harold [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Ruiz, Kathleen A. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Smith, David L. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Weimar, Mark R. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Gardner, Chris [APQC, Houston, TX (United States); Varney, Jeff [APQC, Houston, TX (United States)

    2014-07-01

    A smart grid uses digital power control and communication technology to improve the reliability, security, flexibility, and efficiency of the electric system, from large generation through the delivery systems to electricity consumers and a growing number of distributed generation and storage resources. To convey progress made in achieving the vision of a smart grid, this report uses a set of six characteristics derived from the National Energy Technology Laboratory Modern Grid Strategy. The Smart Grid Status and Metrics Report defines and examines 21 metrics that collectively provide insight into the grid’s capacity to embody these characteristics. This appendix presents papers covering each of the 21 metrics identified in Section 2.1 of the Smart Grid Status and Metrics Report. These metric papers were prepared in advance of the main body of the report and collectively form its informational backbone.

  8. The nutritional selenium status of healthy Greeks.

    Science.gov (United States)

    Bratakos, M S; Kanaki, H C; Vasiliou-Waite, A; Ioannou, P V

    1990-02-01

    The nutritional selenium status of apparently healthy Greeks has been assessed by measuring fluorimetrically the selenium content of whole blood, morning urine, hair and finger nails. The means and standard deviations were 165 +/- 33, 25 +/- 7 ng Se ml-1, 416 +/- 86, and 536 +/- 91 ng Se g-1, respectively. No significant difference was found between the selenium content of whole blood, hair and finger nails, but, for morning urine, there was a significant difference between males and females. The young and the elderly have less selenium in these biological materials than other Greeks. Whole blood selenium correlates significantly with morning urine, hair, and finger nail selenium, as does hair and nail selenium of male, female and male + female Greeks. The results are compared with those in the literature and possible explanations for the observations are presented. It is concluded that the selenium status of Greeks is satisfactory.

  9. Prallethrin Poisoning Presenting as Status Epilepticus

    Directory of Open Access Journals (Sweden)

    D Vijayaraju

    2014-02-01

    Full Text Available Mosquito repellents contain pyrethroid derivatives, as the active ingredient. Data regarding human toxicity following oral intake is limited. This is a case report of an individual who presented with neurotoxicity following oral ingestion of prallethrin (2.4% w/w of a higher concentration present in formulations commercially available than previously. A 22 year old male presented to the emergency Room (ER in status epilepticus. He was managed in the Intensive Care Unit (ICU. No cause for his status could be determined after all laboratory investigations. A review of history with the patient revealed that he had ingested a bottle of liquid mosquito repellent (45 ml. The patient has had no further symptoms on follow up and has been off anti epileptics. Pyrethroid containing mosquito repellents act on neuronal sodium channels causing hyperexcitiability. With no known specific antidotes, symptomatic treatment is the main stay of management.

  10. Iron status and the female athlete.

    Science.gov (United States)

    McClung, James P

    2012-06-01

    Iron deficiency (ID) is the most prevalent micronutrient deficiency disorder in the world. In the developed world, the greatest prevalence of ID and iron deficiency anemia (IDA) occurs in premenopausal women. Premenopausal women experience ID and IDA due to inadequate consumption of dietary iron coupled with iron losses through physiologic processes such as menstruation. Further, female athletes may experience an elevated risk of ID and IDA, as hepcidin, a peptide hormone that inhibits iron absorption and sequesters iron in the macrophage, may rise in response to physical activity. Declines in physical and cognitive performance have been demonstrated in female athletes with ID and IDA. Performance decrements are attenuated as iron status improves. This review will focus on iron status in female athletes, and will include a review of nutritional countermeasures to prevent ID and IDA.

  11. Current Status on Cholangiocarcinoma and Gallbladder Cancer

    Science.gov (United States)

    Ebata, Tomoki; Ercolani, Giorgio; Alvaro, Domenico; Ribero, Dario; Di Tommaso, Luca; Valle, Juan W.

    2016-01-01

    Background Cholangiocarcinomas (CC) as well as gallbladder cancers are relatively rare and intractable diseases. Clinical, pathological, and epidemiological studies on these tumors have been under investigation. The current status and/or topics on biliary tract cancers have been reported in the East West Association of Liver Tumor (EWALT), held in Milano, Italy in 2015. Summary All the authors, herein, specifcally reported the current status and leading-edge findings on biliary tract cancers as the following sequence: epidemiology of CC, surgical therapy for intrahepatic CC, surgical therapy for perihilar CC, surgical therapy for gallblad der cancer, chemotherapy for biliary tract cancers, and new histological features in CC. Key Message The present review article will update the knowledge on biliary tract cancers, en hancing the quality of daily clinical practice. However, many features about these cancers remain unknown; further studies are required to establish disease-specific optimal treatment strategies. PMID:27995089

  12. Midazolam and pentobarbital for refractory status epilepticus.

    Science.gov (United States)

    Holmes, G L; Riviello, J J

    1999-04-01

    Status epilepticus, a serious, life-threatening emergency characterized by prolonged seizure activity, occurs most commonly in pediatric patients. Although initial therapies with agents such as diazepam, phenytoin, or phenobarbital generally terminate seizure activity within 30-60 minutes, patients with refractory status epilepticus (RSE) lasting longer require additional intervention. High-dose pentobarbital has been the most commonly prescribed agent for the management of RSE in children; however, midazolam has emerged as a new treatment option. This review compares the use of midazolam with pentobarbital in published reports of pediatric RSE. Both drugs effectively terminated refractory seizure activity, although pentobarbital use was complicated by hypotension, delayed recovery, pneumonia, and other adverse effects. Midazolam use was effective and well tolerated, affirming its value in pediatric RSE management.

  13. Nutritional status and cognitive impairment in elderly.

    Science.gov (United States)

    Daradkeh, Ghazi; Essa, Musthafa M; Al-Adawi, S Samir; Koshy, Roopa P; Al-Asmi, Abdullah; Waly, Mostafa I

    2014-10-01

    The elderly population is increasing worldwide and it has been suggested that senior citizens will continue to constitute the bulk of the population in many countries. Nutritional status of senior citizens are adversely affected by their frailty, chronic condition and declining cognitive functioning. Conversely, malnourished elderly further deteriorate their frailty, chronic disease and cognitive functioning. The aim of this review article is to recognize the importance of nutritional assessment of elderly population particularly those with cognitive impairment. First part is to highlight characteristic cognitive impairment among senior citizens and the second one highlight t he background in which malnutrition is a factor that leads to increased risk of morbidity and mortality in the elderly. This review also highlight salgorithms for safeguarding nutritional status among senior citizen and focuses on importance of nutritional screening, assessment and early intervention for safeguarding further deterioration of elderly who are likely to prone to cognitive impairment.

  14. Reflections on the Academic Status of Lexicography

    DEFF Research Database (Denmark)

    Tarp, Sven

    2010-01-01

    Two main camps have been formed with regard to the philosophical and academic status of lexicography: one considering lexicography an independent scientific discipline, and the other opposing such a scientific status. This article discusses some of the arguments from the sec¬ond camp and argues...... that lexicography should be considered an independent scientific discipline. The argumentation is based on the fact that the subject field of lexicography is different from the subject fields of any other discipline, including linguistics. In this sense, the concept of a lexico¬graphical work is broader than...... and knowledge. The theory and science of lexicography should not focus on the differences regarding the specific content of all these works, but on aspects that unite them and are common to all of them. In this regard, some of the core characteristics of lexicography as an independent discipline are discussed...

  15. Nutritional Status Assessment (SMO -16E)

    Science.gov (United States)

    Smith, Scott M.; Heer, M. A.; Zwart, S. R.

    2012-01-01

    The Nutritional Status Assessment Supplemental Medical Objective was an experiment initiated to expand nominal pre- and postflight clinical nutrition testing, and to gain a better understanding of the time course of changes during flight. The primary activity of this effort was collecting blood and urine samples 5 times during flight for analysis after return to Earth. Samples were subjected to a battery of tests, including nutritional, physiological, general chemistry, and endocrinology indices. These data provide a comprehensive survey of how nutritional status and related systems are affected by 4-6 months of space flight. Analyzing the data will help us to define nutritional requirements for long-duration missions, and better understand human adaptation to microgravity. This expanded set of measurements will also aid in the identification of nutritional countermeasures to counteract, for example, the deleterious effects of microgravity on bone and muscle and the effects of space radiation.

  16. Life cycle responses to health insurance status.

    Science.gov (United States)

    Pelgrin, Florian; St-Amour, Pascal

    2016-09-01

    This paper studies the lifetime effects of exogenous changes in health insurance coverage (e.g. Medicare, PPACA, termination of employer-provided plans) on the dynamic optimal allocation (consumption, leisure, health expenditures), status (health and wealth), and welfare. We solve, simulate, and structurally estimate a parsimonious life cycle model with endogenous exposure to morbidity and mortality risks, and exogenous health insurance. By varying coverage, we identify the marginal effects of insurance when young and/or when old on allocations, statuses, and welfare. Our results highlight positive effects of insurance on health, wealth and welfare, as well as mid-life substitution away from healthy leisure in favor of more health expenses, caused by peaking wages, and accelerating health issues.

  17. Status of the SPIRAL2 injector commissioning

    Energy Technology Data Exchange (ETDEWEB)

    Thuillier, T., E-mail: thuillier@lpsc.in2p3.fr; Angot, J.; Jacob, J.; Lamy, T.; Sole, P. [LPSC, Université Grenoble Alpes, CNRS/IN2P3, 53 rue des Martyrs, 38026 Grenoble Cedex (France); Barué, C.; Bertrand, P.; Canet, C.; Ferdinand, R.; Flambard, J.-L.; Jardin, P.; Lemagnen, F.; Maunoury, L.; Osmond, B. [GANIL, CNRS/IN2P3, Bvd Henri Becquerel, BP 55027, 14076 Caen Cedex 5 (France); Biarrotte, J. L. [IPN Orsay, Université Paris Sud, CNRS/IN2P3, 15 rue Georges Clémenceau, 91406 Orsay Cedex (France); Denis, J.-F.; Roger, A.; Touzery, R.; Tuske, O.; Uriot, D. [Irfu, CEA Saclay, DSM/Irfu/SACM, 91191 Gif Sur Yvette (France); and others

    2016-02-15

    The SPIRAL2 injector, installed in its tunnel, is currently under commissioning at GANIL, Caen, France. The injector is composed of two low energy beam transport lines: one is dedicated to the light ion beam production, the other to the heavy ions. The first light ion beam, created by a 2.45 GHz electron cyclotron resonance ion source, has been successfully produced in December 2014. The first beam of the PHOENIX V2 18 GHz heavy ion source was analyzed on 10 July 2015. A status of the SPIRAL2 injector commissioning is given. An upgrade of the heavy ion source, named PHOENIX V3 aimed to replace the V2, is presented. The new version features a doubled plasma chamber volume and the high charge state beam intensity is expected to increase by a factor of 1.5 to 2 up to the mass ∼50. A status of its assembly is proposed.

  18. Nutritional status of students in public schools

    Directory of Open Access Journals (Sweden)

    Ivana Lopes de Carvalho

    2014-06-01

    Full Text Available The study assessed the nutrition status of public school students in the city of Carinhanha, state of Bahia, Brazil. It was a cross-sectional study made in 2012, with 224 students from 6 to 9 years of age, of both sexes, mostly from families of low socioeconomic level. The nutrition status was assessed by checking weight and height According to the body mass index per age, malnutrition was observed in 3.6% of the students, overweight in 7.6% and obesity in 5.8%. A tendency towards overweight was observed in 13.4% of the students. Concerning the relation height/age, it was adequate in 218 students (97.3%. These results indicate that the public elementary school students assessed showed a tendency towards overweight, and strategies that promote their health through adequate nutrition must be implemented.

  19. Mild Cognitive Impairment Status and Mobility Performance

    DEFF Research Database (Denmark)

    Pedersen, Mette; Holt, Nicole E; Grande, Laura

    2014-01-01

    BACKGROUND: The prevalence of mild cognitive impairment (MCI) and mobility limitations is high among older adults. The aim of this study was to investigate the association between MCI status and both performance-based and self-report measures of mobility in community-dwelling older adults. METHODS......MCI), nonmemory domains (naMCI), and multiple domains (mdMCI). Linear regression models were used to assess the association between MCI status and mobility performance in the Habitual Gait Speed, Figure of 8 Walk, Short Physical Performance Battery, and self-reported Late Life Function and Disability Instrument......). All MCI subtypes performed significantly worse than No-MCI on all mobility measures (p Figure of 8 Walk (p = .054) and Basic Lower Extremity (p = .11). Moreover, compared with aMCI, mdMCI manifested worse performance on the Figure of 8 Walk and Short...

  20. Current status of the Brazilian AMS program

    Energy Technology Data Exchange (ETDEWEB)

    Gomes, P.R.S. E-mail: paulogom@if.uff.br; Anjos, R.M.; Acquadro, J.C.; Santos, G.M.; Macario, K.D.; Liguori Neto, R.; Added, N.; Coimbra, M.M.; Appoloni, C.R.; Castro Faria, N.V. de; Magalhaes, S.D.; Donangelo, R

    2000-10-01

    The status and the near future plans for the Brazilian AMS program are described. The 8 MV Tandem accelerator at the University of Sao Paulo (USP) is ready to measure standard AMS samples. A recently installed 1.7 MV Tandem at the University of Rio de Janeiro will have a {sup 14}C AMS line. Together with external laboratories, we developed some projects on paleoclimatic and maritime geology. During these studies we have also learned sample preparation procedures.

  1. Technological status of organic photovoltaics (OPV)

    DEFF Research Database (Denmark)

    Carlé, Jon Eggert; Krebs, Frederik C

    2013-01-01

    This paper gives a technological status of organic and polymer photovoltaics (OPV) for both single and tandem junctions. We list the current state-of-the-art at the laboratory level for very small rigid and mostly vacuum processed devices to larger area flexible and printed devices. In comparison...... to other thin film PV the view held is that OPV is at a very early stage of industrial development with future success depending on an application where OPV is uniquely performing....

  2. STATUS KERENTANAN NYAMUK Aedes aegypti TERHADAP MALATHION

    OpenAIRE

    Ratnasari; Ishak, Hasanuddin; Selomo, Makmur

    2016-01-01

    Metode yang digunakan dalam penanggulangan nyamuk Aedes aegypti dewasa adalah dengan menggunakan insektisida jenis organophospat, yaitu malathion melalui fogging (pengasapan). Penelitian ini bertujuan untuk melihat status kerentanan nyamuk Aedes aegypti terhadap malathion 0,8%, 4%, dan 5%.Jenis penelitian yang dilakukan adalah penelitian eksperimental murni dengan rancangan penelitian post-test only with control group design. Jumlah sampel yang digunakan sebesar 1000 nyamuk Aedes aegypti yang...

  3. Small x Phenomenology Summary and Status

    CERN Document Server

    Baranov, S; Ciafaloni, Marcello; Collins, J; Davidsson, M; Gustafson, G; Jung, H; Jönsson, L B; Karlsson, M; Kimber, M A; Kotikov, A V; Kwiecinski, J; Loennblad, L; Miu, G; Salam, Gavin P; Seymour, Michael H; Sjöstrand, Torbjörn; Zotov, N P

    2002-01-01

    The aim of this paper is to summarize the general status of our understanding of small x physics. It is based on presentations and discussions at an informal meeting on this topic held in Lund, Sweden, in March 2001. This document also marks the founding of an informal collaboration between experimentalists and theoreticians with a special interest in small x physics. This paper is dedicated to the memory of Bo Andersson, who died unexpectedly from a heart attack on March 4th, 2002.

  4. Status of KM3NeT

    Directory of Open Access Journals (Sweden)

    Riccobene G.

    2016-01-01

    Full Text Available The recent observation of cosmic neutrinos by IceCube has pushed the quest towards the identification of cosmic sources of high-energy particles. The KM3NeT Collaboration is now ready to launch the massive construction of detection units to be installed in deep sea to build a km-cubic size neutrino telescope. The main elements of the detector, the status of the project and the expected perfomances are briefly reported.

  5. Microbiological status of mechanically separated poultry meat

    OpenAIRE

    Jovanović, Jelena; Borović, Branka; Velebit, Branko; Lakićević, Brankica; Baltić, Tatjana; Mitrović, Radmila; Milijašević, Milan

    2013-01-01

    Mechanically separated meat is often contaminated with microorganisms. The aim of this study was to investigate the microbiological status of mechanically separated poultry meat samples from June 2011 to December 2012. Microbiological testing included Salmonella species, Escherichia coli and the number of aerobic bacteria. In 5.26% of the samples the presence of Salmonella species was revealed, whereas 22.95% and 4.92% of the mechanically separated poultry meat samples were incompliant in reg...

  6. The INTEGRAL Mission: Status and Science

    Science.gov (United States)

    Sturner, Steven J.

    2008-01-01

    Since its launch on October 17, 2002, the INTErnational Gamma-Ray Astrophysics Laboratory (INTEGRAL) mission has been producing exciting scientific results. I will present a brief overview of the INTEGRAL mission including its complement of scientific instruments and its current operational status. This will set the stage for the scientific talks that follow. I will then discuss opportunities for US investigator participation including the NASA INTEGRAL Guest Investigator Program and support services available through the US INTEGRAL Guest Observer Facility.

  7. Functional Status of Patients on Maintenance Hemodialysis

    Directory of Open Access Journals (Sweden)

    Akash Nabil

    1999-01-01

    Full Text Available Factors associated with physical well being were examined in adults with end-stage renal disease (ESRD in two large hemodialysis units of the Royal Medical Services in Jordan. Utilizing the Karnofski scale we measured the functional status of 200 Patients who had been on maintenance hemodialysis for at least 12 months. A Marnofski scale of less than 70 incidents frank disability (Inability to perform routine living activities without assistance, in addition current vocational status was assessed as well as any existing comorbid conditions. The mean age of the study group was 45.2 years (range 16 to 70 and included 108 (54% males and 92 (46% females, there were 39 (19.5% diabetic patients and 27 (13.5% patients were receiving erythropoietin (EPO. The mean hematocrit of the entire group was 27.8%. As measured by Karnofski scale, 64 (32% of the patients were unable to perform routine living activity without assistance; dependence on wheelchair was reported by 9 (4.5% patients. The mean comorbidity index of patients who scored less than 70 on the Karnofski scale was 1.5 compared to 0.7 for those who scored at least 70 on the same scale (p< 0.001. Analysis of factors showed that age and diabetes mellitus affected functional status. Of the laboratory variables measured, only serum albumin concentration correlated significant with Karnofski scale. Fourteen (21.8% of the patients who scored below 70, had serum albumin concentration above 40g/L compared to 66 (48.5% of the patients who scored at least 70 on the Karnofski scale (p< 0.001. We conclude that a significant proportion of patients on maintenance hemodialysis is functionally disabled. The elderly, diabetics, patients with high co-morbidity index and those with low serum albumin are most likely to have poor functional status.

  8. STATUS KESEHATAN IBU HAMIL DI KOTA BEKASI

    Directory of Open Access Journals (Sweden)

    Felly P. Senewe

    2012-11-01

    Full Text Available Women reproductive health is too important to put into consideration because of its health problem related to high risk age group that has great contribution in conducting. The woman health status. Maternal mortality rate in Indonesia is still high. Therefore it is essential to evaluate the achievement of women reproductive health status. The aim of the survey is to evaluate pregnant women health status, concerning antenatal care, delivery assistance, place of delivery, complication, TT immunization, and socioeconomic factor. That can give input for decision making and as baseline data. The survey conducted in the city of Bekasi on September 2002, using cross section design method. Samples consist of all women who have ever been pregnant and giving birth over the past 12 month, with samples amount of 210 women. The survey found that 20% of women during pregnancy were accompanied by nausea or over vomiting. Anemia, head-ache and fatigue were reported for 22%. The coverage of ANC by heath providers was 83% for the first visit and 77% for the fourth visit. TT2 immunization coverage was found 80% and Fe tablet 90%. Most of the respondent visited midwife and medical doctor at clinic during pregnancy. Premature rupture of membranes were reported for 8%, prolonged labor for 6%, and excessive bleeding for 4% during delivery. Eighty-two percent of birth were assisted by medical doctor and midwife. A majority of birth (76% were delivered at midwife's clinic, and only 15% at home. Suggestions, women health care program especially during pregnancy and delivery must have special attention from health care provider; also need good coordination to enhance the coverage. Keywords: pregnant women, health status, reproductive health

  9. LHC detector status and early physics

    CERN Document Server

    Rousseau, D

    2007-01-01

    The current status of LHC machine, and ATLAS and CMS detectors are briefly stated. Expected performance for both detectors is then compared on the main physics objects. The detector understanding studies through combined test beam, cosmics, low energy running one one side, large scale accurate simulation on the other side, are described. Finally, a few physics topics for which the data collected in 2008 will be relevant are mentionned.

  10. Brucellosis in Mexico: current status and trends.

    Science.gov (United States)

    Luna-Martínez, J Eduardo; Mejía-Terán, Claudia

    2002-12-20

    Traditionally, Mexico has been recognized as endemic with brucellosis. The improvements in diagnostics techniques and vaccination strategies and the enforcement of a national eradication policy have contributed significantly to making progress in the control of brucellosis. The current status of brucellosis and its risk factors, in the different production species as well as in human population is reviewed. Also the trends in control and eventual eradication strategies and perspectives for the near future of Mexico are presented.

  11. Current status of iron-based superconductors

    Energy Technology Data Exchange (ETDEWEB)

    Kamihara, Yoichi, E-mail: kamihara_yoichi@appi.keio.ac.jp [Keio University, Department of Applied Physics and Physico-Informatics, Faculty of Science and Technology (Japan)

    2012-03-15

    Current status of iron-based superconductors is summarized. Although short range magnetic ordering and magnetic phase separation of Fe are controversial, (long range) magnetic and electronic phase diagrams of iron based superconductors can be classified into two-type. Antiferromagnetic ordering of itinerant Fe does not coexist with superconducting phase of SmFeAsO{sub 1 - x}F{sub x}. The very large H{sub c2} of iron-based superconductors attract us to attempts at applications.

  12. Current status of iron-based superconductors

    Science.gov (United States)

    Kamihara, Yoichi

    2012-03-01

    Current status of iron-based superconductors is summarized. Although short range magnetic ordering and magnetic phase separation of Fe are controversial, (long range) magnetic and electronic phase diagrams of iron based superconductors can be classified into two-type. Antiferromagnetic ordering of itinerant Fe does not coexist with superconducting phase of SmFeAsO1 - xFx. The very large H c2 of iron-based superconductors attract us to attempts at applications.

  13. Lung xenotransplantation: recent progress and current status.

    Science.gov (United States)

    Harris, Donald G; Quinn, Kevin J; Dahi, Siamak; Burdorf, Lars; Azimzadeh, Agnes M; Pierson, Richard N

    2014-01-01

    Xenotransplantation has undergone important progress in controlling initial hyperacute rejection in many preclinical models, with some cell, tissue, and organ xenografts advancing toward clinical trials. However, acute injury, driven primarily by innate immune and inflammatory responses, continues to limit results in lung xenograft models. The purpose of this article is to review the current status of lung xenotransplantation--including the seemingly unique challenges posed by this organ-and summarize proven and emerging means of overcoming acute lung xenograft injury.

  14. Intensive care management of status epilepticus

    OpenAIRE

    2016-01-01

    Status epilepticus (SE) is a life-threatening neurological emergency that requires prompt diagnosis and treatment. SE may be classified into convulsive and non-convulsive types, based on the presence of rhythmic jerking of the extremities. Clinically, tonic-clonic convulsive SE (CSE) is divided into four subsequent stages: Early, established, refractory and super-refractory. Initial elements of resuscitation include airway protection, haemodynamic resuscitation and seizure control. Further tr...

  15. Ketamine in status asthmaticus: A review

    Directory of Open Access Journals (Sweden)

    Shweta Goyal

    2013-01-01

    Full Text Available Background and Aims : Status asthmaticus is a common cause of morbidity and mortality. The addition of ketamine to the standard treatment regimen of severe asthma has shown to improve outcome and alleviate the need for mechanical ventilation. The purpose of this review is to determine the pulmonary effects of ketamine and to determine whether sufficient evidence exists to support its use for refractory status asthmaticus. Data Source: MEDLINE, EMBASE, Google Scholar, and Cochrane data bases (from their inception to Jan 2012 using key words "ketamine," "asthma," "bronchospasm," "bronchodilator," and "mechanical ventilation" were searched to identify the reports on the use of ketamine as a bronchodilator in acute severe asthma or status asthmaticus, and manual review of article bibliographies was done. Relevant databases were searched for the ongoing trials on use of ketamine as a bronchodilator. Outcome measures were analyzed using following clinical questions: Indication, dose and duration of ketamine use, main effects on respiratory mechanics, adverse effects, and mortality. Results: Twenty reports illustrating the use of ketamine as a bronchodilator were identified. In total, 244 patients aged 5 months to 70 years received ketamine for bronchospasm. Twelve case reports, 3 double-blind randomized placebo-controlled trials, 2 prospective observational studies, 2 clinical evaluation study, and 1 retrospective chart review were retrieved. Most of the studies showed improved outcome with use of ketamine in acute severe asthma unresponsive to conventional treatment. Patients who received ketamine improved clinically, had lower oxygen requirements, and obviated the need for invasive ventilation. Mechanically-ventilated patients for severe bronchospasm showed reduction in peak inspiratory pressures, improved gas exchange, dynamic compliance and minute ventilation, and could be weaned off successfully following introduction of ketamine. Conclusion: In

  16. Current status of fast reactor physics

    Energy Technology Data Exchange (ETDEWEB)

    Hummel, H.H.

    1979-01-01

    The subject of calculation of reactivity coefficients for fast reactors is developed, starting with a discussion of the status of relevant nuclear data and proceeding to the subjects of group cross section generation and of methods of obtaining reactivity coefficients from group cross sections. Reactivity coefficients measured in critical experiments are compared with calculated values. Dependence of reactivity coefficients on reactor design is discussed. Finally, results of the recent international comparison of calculated reactivity coefficients are presented.

  17. The status of fuel cell technology

    Energy Technology Data Exchange (ETDEWEB)

    O' Sullivan, J.B.

    1991-02-20

    This brief status report provides an introduction to what fuel cells are, why they are important, what uses have been made of them to date, the goals and timetables of current programs, and who the players are in this vital technology. Copies of most of the slides presented and additional diagrams are appended to this paper. Further details can be obtained from the comprehensive texts cited in the bibliography. 11 refs., 44 figs.

  18. Nova pulse power system description and status

    Energy Technology Data Exchange (ETDEWEB)

    Holloway, R.W.; Whitham, K.; Merritt, B.T.; Gritton, D.G.; Oicles, J.A.

    1981-06-01

    The Nova laser system is designed to produce critical data in the nation's inertial confinement fusion effort. It is the world's largest peak power laser and presents various unique pulse power problems. In this paper, pulse power systems for this laser are described, the evolutionary points from prior systems are pointed out, and the current status of the hardware is given.

  19. French Flight Test Program LEA Status

    Science.gov (United States)

    2010-09-01

    reusable . French Flight Test Program LEA Status RTO-EN-AVT-185 17 - 5 Figure 4: CAD view of LEA vehicle. The test principle consists in...Figure 8: CLEA model under test at ONERA test facility. Some parametric studies related to forebody have been carried out in order to determine a...PROPULSION: ENGINE DESIGN – INTEGRATION AND THERMAL MANAGEMENT” is focused on the French flight experiment program called “LEA”. French R&T effort

  20. Status over revisionsforskningen i Danmark (1)

    DEFF Research Database (Denmark)

    Seehausen, Jesper; Holm, Claus

    2005-01-01

    virke. I artiklen gør ph.d.-studerende, cand.merc.aud. Jesper Seehausen fra Aalborg Universitet og lektor, ph.d. Claus Holm fra Handelshøjskolen i Århus status over revisionsforskningen i Danmark. Der fokuseres på den forskning, som gennemføres og publiceres i form af ph.d.-afhandlinger. I nærværende...

  1. Fra amt til region: Status og udviklingsperspektiver

    DEFF Research Database (Denmark)

    Pallesen, Thomas

      Den 1. januar 2007 nedlægges de nuværende amter og erstattes af regionerne. Det er en passende anledning til at gøre status over amternes indsats. Artiklens hovedkonklusion er, at amterne gjorde det godt, især fordi det lykkedes dem at sikre en mådeholden økonomisk udvikling på sygehusområdet...

  2. Status over revisionsforskningen i Danmark (2)

    DEFF Research Database (Denmark)

    Seehausen, Jesper; Holm, Claus

    2005-01-01

    for revisors virke. I artiklen gør ph.d.-studerende, cand.merc.aud. Jesper Seehausen fra Aalborg Universitet og lektor, ph.d. Claus Holm fra Handelshøjskolen i Århus status over revisionsforskningen i Danmark. Der fokuseres på den forskning, som gennemføres og publiceres i form af ph.d.-afhandlinger. I første...

  3. ACRF Instrumentation Status and Information April 2009

    Energy Technology Data Exchange (ETDEWEB)

    Voyles, JW

    2009-05-07

    The purpose of this report is to provide a concise but comprehensive overview of Atmospheric Radiation Measurement Climate Research Facility instrumentation status. The report is divided into the following five sections: (1) new instrumentation in the process of being acquired and deployed, (2) field campaigns, (3) existing instrumentation and progress on improvements or upgrades, (4) proposed future instrumentation, and (5) Small Business Innovation Research instrument development.

  4. ACRF Instrumentation Status and Information May 2009

    Energy Technology Data Exchange (ETDEWEB)

    JW Voyles

    2009-05-01

    The purpose of this report is to provide a concise but comprehensive overview of Atmospheric Radiation Measurement Climate Research Facility instrumentation status. The report is divided into the following five sections: (1) new instrumentation in the process of being acquired and deployed, (2) field campaigns, (3) existing instrumentation and progress on improvements or upgrades, (4) proposed future instrumentation, and (5) Small Business Innovation Research instrument development.

  5. ACRF Instrumentation Status and Information July 2009

    Energy Technology Data Exchange (ETDEWEB)

    JW Voyles

    2009-08-13

    The purpose of this report is to provide a concise but comprehensive overview of Atmospheric Radiation Measurement Climate Research Facility instrumentation status. The report is divided into the following five sections: (1) new instrumentation in the process of being acquired and deployed, (2) field campaigns, (3) existing instrumentation and progress on improvements or upgrades, (4) proposed future instrumentation, and (5) Small Business Innovation Research instrument development.

  6. ACRF Instrumentation Status and Information - June 2009

    Energy Technology Data Exchange (ETDEWEB)

    JW Voyles

    2009-06-01

    The purpose of this report is to provide a concise but comprehensive overview of Atmospheric Radiation Measurement Climate Research Facility instrumentation status. The report is divided into the following five sections: (1) new instrumentation in the process of being acquired and deployed, (2) field campaigns, (3) existing instrumentation and progress on improvements or upgrades, (4) proposed future instrumentation, and (5) Small Business Innovation Research instrument development.

  7. ACRF Instrumentation Status and Information September 2009

    Energy Technology Data Exchange (ETDEWEB)

    JW Voyles

    2009-10-01

    The purpose of this report is to provide a concise but comprehensive overview of Atmospheric Radiation Measurement Climate Research Facility instrumentation status. The report is divided into the following five sections: (1) new instrumentation in the process of being acquired and deployed, (2) field campaigns, (3) existing instrumentation and progress on improvements or upgrades, (4) proposed future instrumentation, and (5) Small Business Innovation Research instrument development.

  8. ACRF Instrumentation Status and Information August 2009

    Energy Technology Data Exchange (ETDEWEB)

    JW Voyles

    2009-09-09

    The purpose of this report is to provide a concise but comprehensive overview of Atmospheric Radiation Measurement Climate Research Facility instrumentation status. The report is divided into the following five sections: (1) new instrumentation in the process of being acquired and deployed, (2) field campaigns, (3) existing instrumentation and progress on improvements or upgrades, (4) proposed future instrumentation, and (5) Small Business Innovation Research instrument development.

  9. Immunisation status in inner London primary schools.

    OpenAIRE

    Bedford, H E; Masters, J I; Kurtz, Z

    1992-01-01

    In one inner London district health authority, the immunisation status of children attending their routine school entry health interview was reviewed over four terms. During the course of these interviews, school nurses completed a questionnaire with parents that asked for their child's immunisation history and details of family and social background. Parental reporting of immunisation history was compared with district health authority records. Only 56% of children reviewed were found to be ...

  10. Current Status and Future of Sports Food

    OpenAIRE

    Hailong Zhang

    2015-01-01

    According to the need of the popularization of sports nutrition knowledge and promoting of our country sports nutrition needs, the study expounds the new concept of sports nutrition food, the development of sports nutrition food abroad, the prospect of the domestic market and the status quo of cultivate. Sports nutrition food system which has been basically in more than a decade in domestic is made a detailed elaboration and an introduction of product research and development has been made. T...

  11. Smart Grid Status and Metrics Report

    Energy Technology Data Exchange (ETDEWEB)

    Balducci, Patrick J. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Weimar, Mark R. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Kirkham, Harold [Pacific Northwest National Lab. (PNNL), Richland, WA (United States)

    2014-07-01

    To convey progress made in achieving the vision of a smart grid, this report uses a set of six characteristics derived from the National Energy Technology Laboratory Modern Grid Strategy. It measures 21 metrics to provide insight into the grid’s capacity to embody these characteristics. This report looks across a spectrum of smart grid concerns to measure the status of smart grid deployment and impacts.

  12. 24 CFR 5.512 - Verification of eligible immigration status.

    Science.gov (United States)

    2010-04-01

    ... immigration status. 5.512 Section 5.512 Housing and Urban Development Office of the Secretary, Department of... Noncitizens § 5.512 Verification of eligible immigration status. (a) General. Except as described in paragraph...) Primary verification—(1) Automated verification system. Primary verification of the immigration status...

  13. 40 CFR 270.72 - Changes during interim status.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 26 2010-07-01 2010-07-01 false Changes during interim status. 270.72... (CONTINUED) EPA ADMINISTERED PERMIT PROGRAMS: THE HAZARDOUS WASTE PERMIT PROGRAM Interim Status § 270.72 Changes during interim status. (a) Except as provided in paragraph (b), the owner or operator of...

  14. 40 CFR 270.70 - Qualifying for interim status.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 26 2010-07-01 2010-07-01 false Qualifying for interim status. 270.70... (CONTINUED) EPA ADMINISTERED PERMIT PROGRAMS: THE HAZARDOUS WASTE PERMIT PROGRAM Interim Status § 270.70 Qualifying for interim status. (a) Any person who owns or operates an “existing HWM facility” or a...

  15. 8 CFR 207.9 - Termination of refugee status.

    Science.gov (United States)

    2010-01-01

    ... 8 Aliens and Nationality 1 2010-01-01 2010-01-01 false Termination of refugee status. 207.9... REFUGEES § 207.9 Termination of refugee status. The refugee status of any alien (and of the spouse or child... district director in whose district the alien is found if the alien was not a refugee within the meaning...

  16. 7 CFR 273.4 - Citizenship and alien status.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 4 2010-01-01 2010-01-01 false Citizenship and alien status. 273.4 Section 273.4... and alien status. (a) Household members meeting citizenship or alien status requirements. No person is...)(4)(i) of this section, or (5) An individual who is both a qualified alien as defined in paragraph...

  17. 8 CFR 1209.1 - Adjustment of status of refugees.

    Science.gov (United States)

    2010-01-01

    ... 8 Aliens and Nationality 1 2010-01-01 2010-01-01 false Adjustment of status of refugees. 1209.1... IMMIGRATION REGULATIONS ADJUSTMENT OF STATUS OF REFUGEES AND ALIENS GRANTED ASYLUM § 1209.1 Adjustment of status of refugees. The provisions of this section shall provide the sole and exclusive procedure...

  18. 19 CFR 4.7d - Container status messages.

    Science.gov (United States)

    2010-04-01

    ... 19 Customs Duties 1 2010-04-01 2010-04-01 false Container status messages. 4.7d Section 4.7d... TREASURY VESSELS IN FOREIGN AND DOMESTIC TRADES Arrival and Entry of Vessels § 4.7d Container status messages. (a) Container status messages required. In addition to the advance filing requirements...

  19. Aborted and refractory status epilepticus in children : A comparative analysis

    NARCIS (Netherlands)

    Lambrechtsen, Florise A. C. P.; Buchhalter, Jeffrey R.

    2008-01-01

    Purpose: The aims of this retrospective study were: (1) to compare the demographics, clinical characteristics, etiology, and EEG findings of status epilepticus aborted with medication (ASE) and refractory status epilepticus (RSE), (2) to describe the treatment response of status epilepticus (SE), an

  20. Relations between Psychological Status and Eye Movements

    Directory of Open Access Journals (Sweden)

    Kohei Arai

    2015-06-01

    Full Text Available Relations between psychological status and eye movements are found through experiments with readings of different types of documents as well as playing games. Psychological status can be monitored with Electroencephalogram: EEG sensor while eye movements can be monitored with Near Infrared: NIR cameras with NIR Light Emission Diode: LED. EEG signals are suffred from noises while eye movement can be acquired without any influence from nise. Therefore, psychlogical status can be monitored with eye movement detection instead of EEG signal acquisition if there is relation between both. Through the experiments, it is found strong relation between both. In particular, relation between the number of rapid changes of line of sight directions and relatively high frequency components of EEG signals is found. It is also found that the number of rapid eye movement is counted when the users are reading the documents. The rapid eye movement is defined as 10 degrees of look angle difference for one second. Not only when the users change the lines in the document, but also when the users feel a difficulty for reading words in the document, the users’ line of sight direction moves rapidly.