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Sample records for muc1 glycopeptides elicit

  1. Chemoenzymatically synthesized multimeric Tn/STn MUC1 glycopeptides elicit cancer-specific anti-MUC1 antibody responses and override tolerance

    DEFF Research Database (Denmark)

    Sørensen, Anne Louise; Reis, Celso A; Tarp, Mads A

    2005-01-01

    The MUC1 mucin represents a prime target antigen for cancer immunotherapy because it is abundantly expressed and aberrantly glycosylated in carcinomas. Attempts to generate strong humoral immunity to MUC1 by immunization with peptides have generally failed partly because of tolerance. In this stu...

  2. Potential for novel MUC1 glycopeptide-specific antibody in passive cancer immunotherapy

    DEFF Research Database (Denmark)

    Madsen, Caroline B; Wandall, Hans H; Pedersen, Anders Elm

    2013-01-01

    MUC1 is an important target for antibodies in passive cancer immunotherapy. Antibodies against mucin glycans or mucin peptide backbone alone may give rise to cross reactivity with normal tissues. Therefore, attempts to identify antibodies against cancer-specific MUC1 glycopeptide epitopes havebeen...

  3. Epitopes of MUC1 Tandem Repeats in Cancer as Revealed by Antibody Crystallography: Toward Glycopeptide Signature-Guided Therapy

    Directory of Open Access Journals (Sweden)

    Dapeng Zhou

    2018-05-01

    Full Text Available Abnormally O-glycosylated MUC1 tandem repeat glycopeptide epitopes expressed by multiple types of cancer have long been attractive targets for therapy in the race against genetic mutations of tumor cells. Glycopeptide signature-guided therapy might be a more promising avenue than mutation signature-guided therapy. Three O-glycosylated peptide motifs, PDTR, GSTA, and GVTS, exist in a tandem repeat HGVTSAPDTRPAPGSTAPPA, containing five O-glycosylation sites. The exact peptide and sugar residues involved in antibody binding are poorly defined. Co-crystal structures of glycopeptides and respective monoclonal antibodies are very few. Here we review 3 groups of monoclonal antibodies: antibodies which only bind to peptide portion, antibodies which only bind to sugar portion, and antibodies which bind to both peptide and sugar portions. The antigenicity of peptide and sugar portions of glyco-MUC1 tandem repeat were analyzed according to available biochemical and structural data, especially the GSTA and GVTS motifs independent from the most studied PDTR. Tn is focused as a peptide-modifying residue in vaccine design, to induce glycopeptide-binding antibodies with cross reactivity to Tn-related tumor glycans, but not glycans of healthy cells. The unique requirement for the designs of antibody in antibody-drug conjugate, bi-specific antibodies, and chimeric antigen receptors are also discussed.

  4. Autoantibodies to MUC1 glycopeptides cannot be used as a screening assay for early detection of breast, ovarian, lung or pancreatic cancer

    DEFF Research Database (Denmark)

    Burford, B; Gentry-Maharaj, A; Graham, R

    2013-01-01

    Autoantibodies have been detected in sera before diagnosis of cancer leading to interest in their potential as screening/early detection biomarkers. As we have found autoantibodies to MUC1 glycopeptides to be elevated in early-stage breast cancer patients, in this study we analysed these autoanti...

  5. Natural and Induced Humoral Responses to MUC1

    International Nuclear Information System (INIS)

    Mensdorff-Pouilly, Silvia von; Moreno, Maria; Verheijen, René H. M.

    2011-01-01

    MUC1 is a membrane-tethered mucin expressed on the ductal cell surface of glandular epithelial cells. Loss of polarization, overexpression and aberrant glycosylation of MUC1 in mucosal inflammation and in adenocarcinomas induces humoral immune responses to the mucin. MUC1 IgG responses have been associated with a benefit in survival in patients with breast, lung, pancreatic, ovarian and gastric carcinomas. Antibodies bound to the mucin may curb tumor progression by restoring cell-cell interactions altered by tumor-associated MUC1, thus preventing metastatic dissemination, as well as counteracting the immune suppression exerted by the molecule. Furthermore, anti-MUC1 antibodies are capable of effecting tumor cell killing by antibody-dependent cell-mediated cytotoxicity. Although cytotoxic T cells are indispensable to achieve anti-tumor responses in advanced disease, abs to tumor-associated antigens are ideally suited to address minimal residual disease and may be sufficient to exert adequate immune surveillance in an adjuvant setting, destroying tumor cells as they arise or maintaining occult disease in an equilibrium state. Initial evaluation of MUC1 peptide/glycopeptide mono and polyvalent vaccines has shown them to be immunogenic and safe; anti-tumor responses are scarce. Progress in carbohydrate synthesis has yielded a number of sophisticated substrates that include MUC1 glycopeptide epitopes that are at present in preclinical testing. Adjuvant vaccination with MUC1 glycopeptide polyvalent vaccines that induce strong humoral responses may prevent recurrence of disease in patients with early stage carcinomas. Furthermore, prophylactic immunotherapy targeting MUC1 may be a strategy to strengthen immune surveillance and prevent disease in subjects at hereditary high risk of breast, ovarian and colon cancer

  6. Natural and Induced Humoral Responses to MUC1

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    Mensdorff-Pouilly, Silvia von, E-mail: s.vonmensdorff@vumc.nl; Moreno, Maria [Department of Obstetrics and Gynecology, VU University Medical Center, De Boelelaan 1117, Amsterdam 1081 HV (Netherlands); Verheijen, René H. M. [Department of Woman & Baby, Division of Surgical & Oncological Gynaecology, University Medical Center Utrecht, Heidelberglaan 100, Utrecht 3508 GA (Netherlands)

    2011-07-29

    MUC1 is a membrane-tethered mucin expressed on the ductal cell surface of glandular epithelial cells. Loss of polarization, overexpression and aberrant glycosylation of MUC1 in mucosal inflammation and in adenocarcinomas induces humoral immune responses to the mucin. MUC1 IgG responses have been associated with a benefit in survival in patients with breast, lung, pancreatic, ovarian and gastric carcinomas. Antibodies bound to the mucin may curb tumor progression by restoring cell-cell interactions altered by tumor-associated MUC1, thus preventing metastatic dissemination, as well as counteracting the immune suppression exerted by the molecule. Furthermore, anti-MUC1 antibodies are capable of effecting tumor cell killing by antibody-dependent cell-mediated cytotoxicity. Although cytotoxic T cells are indispensable to achieve anti-tumor responses in advanced disease, abs to tumor-associated antigens are ideally suited to address minimal residual disease and may be sufficient to exert adequate immune surveillance in an adjuvant setting, destroying tumor cells as they arise or maintaining occult disease in an equilibrium state. Initial evaluation of MUC1 peptide/glycopeptide mono and polyvalent vaccines has shown them to be immunogenic and safe; anti-tumor responses are scarce. Progress in carbohydrate synthesis has yielded a number of sophisticated substrates that include MUC1 glycopeptide epitopes that are at present in preclinical testing. Adjuvant vaccination with MUC1 glycopeptide polyvalent vaccines that induce strong humoral responses may prevent recurrence of disease in patients with early stage carcinomas. Furthermore, prophylactic immunotherapy targeting MUC1 may be a strategy to strengthen immune surveillance and prevent disease in subjects at hereditary high risk of breast, ovarian and colon cancer.

  7. MUC1-specific immune therapy generates a strong anti-tumor response in a MUC1-tolerant colon cancer model.

    Science.gov (United States)

    Mukherjee, P; Pathangey, L B; Bradley, J B; Tinder, T L; Basu, G D; Akporiaye, E T; Gendler, S J

    2007-02-19

    A MUC1-based vaccine was used in a preclinical model of colon cancer. The trial was conducted in a MUC1-tolerant immune competent host injected with MC38 colon cancer cells expressing MUC1. The vaccine included: MHC class I-restricted MUC1 peptides, MHC class II-restricted pan-helper-peptide, unmethylated CpG oligodeoxynucleotide, and granulocyte macrophage-colony stimulating factor. Immunization was successful in breaking MUC1 self-tolerance, and in eliciting a robust anti-tumor response. The vaccine stimulated IFN-gamma-producing CD4(+) helper and CD8(+) cytotoxic T cells against MUC1 and other undefined MC38 tumor antigens. In the prophylactic setting, immunization caused complete rejection of tumor cells, while in the therapeutic regimen, tumor burden was significantly reduced.

  8. Autoantibodies to aberrantly glycosylated MUC1 in early stage breast cancer are associated with a better prognosis

    DEFF Research Database (Denmark)

    Blixt, Ola; Bueti, Deanna; Burford, Brian

    2011-01-01

    associated glycoforms of MUC1 in a proportion of early breast cancer patients (54/198). Five positive sera were selected for detailed definition of the reactive epitopes using on chip glycosylation technology and a panel of glycopeptides based on a single MUC1 tandem repeat carrying specific glycans...

  9. The Use of Fluoroproline in MUC1 Antigen Enables Efficient Detection of Antibodies in Patients with Prostate Cancer

    NARCIS (Netherlands)

    Somovilla, Víctor J; Bermejo, Iris A.; Albuquerque, Inês S; Martínez-Sáez, Nuria; Castro-López, Jorge; García-Martín, Fayna; Compañón, Ismael; Hinou, Hiroshi; Nishimura, Shin-Ichiro; Jiménez-Barbero, Jesús; Asensio, Juan L.; Avenoza, Alberto; Busto, Jesús H.; Hurtado-Guerrero, Ramón; Peregrina, Jesús M.; Bernardes, Gonçalo J L; Corzana, Francisco

    2017-01-01

    A structure-based design of a new generation of tumor-associated glycopeptides with improved affinity against two anti-MUC1 antibodies is described. These unique antigens feature a fluorinated proline residue, such as a (4S)-4-fluoro-l-proline or 4,4-difluoro-l-proline, at the most immunogenic

  10. MUC1-specific CTLs are non-functional within a pancreatic tumor microenvironment.

    Science.gov (United States)

    Mukherjee, P; Ginardi, A R; Madsen, C S; Tinder, T L; Jacobs, F; Parker, J; Agrawal, B; Longenecker, B M; Gendler, S J

    2001-01-01

    Pancreatic cancer is a highly aggressive, treatment refractory disease and is the fourth leading cause of death in the United States. In humans, 90% of pancreatic adenocarcinomas over-express altered forms of a tumor-associated antigen, MUC1 (an epithelial mucin glycoprotein), which is a target for immunotherapy. Using a clinically relevant mouse model of pancreas cancer that demonstrates peripheral and central tolerance to human MUC1 and develops spontaneous tumors of the pancreas, we have previously reported the presence of functionally active, low affinity, MUC1-specific precursor cytotoxic T cells (pCTLs). Hypothesis for this study is that MUC1-based immunization may enhance the low level MUC1-specific immunity that may lead to an effective anti-tumor response. Data demonstrate that MUC1 peptide-based immunization elicits mature MUC1-specific CTLs in the peripheral lymphoid organs. The mature CTLs secrete IFN-gamma and are cytolytic against MUC1-expressing tumor cells in vitro. However, active CTLs that infiltrate the pancreas tumor microenvironment become cytolytically anergic and are tolerized to MUC1 antigen, allowing the tumor to grow. We demonstrate that the CTL tolerance could be reversed at least in vitro with the use of anti-CD40 co-stimulation. The pancreas tumor cells secrete immunosuppressive cytokines, including IL-10 and TGF-beta that are partly responsible for the down-regulation of CTL activity. In addition, they down-regulate their MHC class I molecules to avoid immune recognition. CD4+ CD25+ T regulatory cells, which secrete IL-10, were also found in the tumor environment. Together these data indicate the use of several immune evasion mechanisms by tumor cells to evade CTL killing. Thus altering the tumor microenvironment to make it more conducive to CTL killing may be key in developing a successful anti-cancer immunotherapy.

  11. Androgen-Dependent Regulation of Human MUC1 Mucin Expression

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    Stephen Mitchell

    2002-01-01

    Full Text Available MUC1 mucin is transcriptionally regulated by estrogen, progesterone, and glucocorticoids. Our objective was to determine whether androgen receptor. (20AR activation regulates expression of MUC1. The following breast and prostatic cell lines were phenotyped and grouped according to AR and MUC1protein expression: 1 AR+MUCi + [DAR17+19. (20AR transfectants of DU-145, ZR-75-1, MDA-MB-453, and T47D]; 2 AR-MUCi+ [DZeoi. (20AR- vector control, DU-145, BT20, MDA-MB231, and MCF7]; 3 AIR +MUCi -. (20LNCaP and LNCaP-r. Cell proliferation was determined using the MTT assay in the presence of synthetic androgen R1881, 0.1 pM to 1 µM. Cell surface MUC1expression was determined by flow cytometry in the presence or absence of oestradiol, medroxy progesterone acetate or R1881, with and without 4 hydroxy-flutamide. (204-OH, a nonsteroidal AR antagonist. The functional significance of MUC1expression was investigated with a cell-cell aggregation assay. Only AR+ MUC1 + cell lines showed a significant increase in MUC1expression with AR activation. (20P. (20range =.01 to .0001, reversed in the presence of 4-OHF. Cell proliferation was unaffected. Increased expression of MUC1was associated with a significant. (20P. (20range =.002 to .001 reduction in cell-cell adhesion. To our knowledge, this is the first description of androgen-dependent regulation of MUC1mucin. This is also functionally associated with decreased cell-cell adhesion, a recognised feature of progressive malignancy. These findings have important implications for physiological and pathological processes.

  12. Seromic profiling of colorectal cancer patients with novel glycopeptide microarray

    DEFF Research Database (Denmark)

    Pedersen, Johannes W; Blixt, Ola; Bennett, Eric P

    2011-01-01

    -translational modifications (PTMs). Short aberrant O-glycans on proteins may introduce novel glycopeptide epitopes that can elicit autoantibodies because of lack of tolerance. Technical barriers, however, have hampered detection of such glycopeptide-specific autoantibodies. Here, we have constructed an expanded glycopeptide...... using novel monoclonal antibodies. Our study provides evidence for the value of glycopeptides and other PTM-peptide arrays in diagnostic measures....

  13. Tumor-associated Tn-MUC1 glycoform is internalized through the macrophage galactose-type C-type lectin and delivered to the HLA class I and II compartments in dendritic cells

    DEFF Research Database (Denmark)

    Napoletano, Chiara; Rughetti, Aurelia; Agervig Tarp, Mads P

    2007-01-01

    . This results in the expression of tumor-associated glycoforms and in MUC1 carrying the tumor-specific glycan Tn (GalNAcalpha1-O-Ser/Thr). Glycopeptides corresponding to three tandem repeats of MUC1, enzymatically glycosylated with 9 or 15 mol of GalNAc, were shown to specifically bind and to be internalized...... and ELISA done on subcellular fractions of iDCs showed that the Tn-MUC1 glycopeptides colocalized with HLA class I and II compartments after internalization. Importantly, although Tn-MUC1 recombinant protein was bound and internalized by MGL, the glycoprotein entered the HLA class II compartment......, but not the HLA class I pathway. These data indicate that MGL expressed on iDCs is an optimal receptor for the internalization of short GalNAcs carrying immunogens to be delivered into HLA class I and II compartments. Such glycopeptides therefore represent a new way of targeting the HLA class I and II pathways...

  14. MUC1 expression and anti-MUC1 serum immune response in head and neck squamous cell carcinoma (HNSCC): a multivariate analysis

    International Nuclear Information System (INIS)

    Rabassa, Martín E; Croce, María V; Pereyra, Adrián; Segal-Eiras, Amada

    2006-01-01

    HNSCC progression to adjacent tissue and nodes may be mediated by altered glycoproteins and glycolipids such as MUC1 mucin. This report constitutes a detailed statistical study about MUC1 expression and anti-MUC1 immune responses in relation to different clinical and pathological parameters which may be useful to develop new anti HNSCC therapeutic strategies. Fifty three pre treatment HNSCC patients were included: 26 (49.1%) bearing oral cavity tumors, 17 (32.1%) localized in the larynx and 10 (18.8%) in the pharynx. Three patients (5.7%) were at stage I, 5 (9.4%) stage II, 15 (28.3%) stage III and 30 (56.6%) at stage IV. MUC1 tumor expression was studied by immunohistochemistry employing two anti-MUC1 antibodies: CT33, anti cytoplasmic tail MUC1 polyclonal antibody (Ab) and C595 anti-peptidic core MUC1 monoclonal antibody. Serum levels of MUC1 and free anti-MUC1 antibodies were detected by ELISA and circulating immune complexes (CIC) by precipitation in polyethylene glycol (PEG) 3.5%; MUC1 isolation from circulating immune complexes was performed by protein A-sepharose CL-4B affinity chromatography followed by SDS-PAGE and Western blot. Statistical analysis consisted in Multivariate Principal Component Analysis (PCA); ANOVA test (Tukey's test) was employed to find differences among groups; nonparametrical correlations (Kendall's Tau) were applied when necessary. Statistical significance was set to p < 0.05 in all cases. MUC1 cytoplasmic tail was detected in 40/50 (80%) and MUC1 protein core in 9/50 (18%) samples while serum MUC1 levels were elevated in 8/53 (15%) patients. A significant statistical correlation was found between MUC1 serum levels and anti-MUC1 IgG free antibodies, while a negative correlation between MUC1 serum levels and anti-MUC1 IgM free antibodies was found. Circulating immune complexes were elevated in 16/53 (30%) samples and were also statistically associated with advanced tumor stage. MUC1 was identified as an antigenic component

  15. Analysis of a cholera toxin B subunit (CTB) and human mucin 1 (MUC1) conjugate protein in a MUC1-tolerant mouse model.

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    Pinkhasov, Julia; Alvarez, M Lucrecia; Pathangey, Latha B; Tinder, Teresa L; Mason, Hugh S; Walmsley, Amanda M; Gendler, Sandra J; Mukherjee, Pinku

    2010-12-01

    Since epithelial mucin 1 (MUC1) is associated with several adenocarcinomas at the mucosal sites, it is pertinent to test the efficacy of a mucosally targeted vaccine formulation. The B subunit of the Vibrio cholerae cholera toxin (CTB) has great potential to act as a mucosal carrier for subunit vaccines. In the present study we evaluated whether a MUC1 tandem repeat (TR) peptide chemically linked to CTB would break self-antigen tolerance in the transgenic MUC1-tolerant mouse model (MUC1.Tg) through oral or parenteral immunizations. We report that oral immunization with the CTB-MUC1 conjugate along with mucosal adjuvant, unmethylated CpG oligodeoxynucleotide (ODN) and interleukin-12 (IL-12) did not break self-antigen tolerance in MUC1.Tg mice, but induced a strong humoral response in wild-type C57BL/6 mice. However, self-antigen tolerance in the MUC1.Tg mouse model was broken after parenteral immunizations with different doses of the CTB-MUC1 conjugate protein and with the adjuvant CpG ODN co-delivered with CTB-MUC1. Importantly, mice immunized systemically with CpG ODN alone and with CTB-MUC1 exhibited decreased tumor burden when challenged with a mammary gland tumor cell line that expresses human MUC1.

  16. Analysis of a Cholera Toxin B Subunit (CTB) and Human Mucin 1 (MUC1) Conjugate Protein in a MUC1 Tolerant Mouse Model

    Science.gov (United States)

    Pinkhasov, Julia; Alvarez, M. Lucrecia; Pathangey, Latha B.; Tinder, Teresa L.; Mason, Hugh S.; Walmsley, Amanda M.; Gendler, Sandra J.; Mukherjee, Pinku

    2011-01-01

    Since epithelial mucin 1 (MUC1) is associated with several adenocarcinomas at mucosal sites, it is pertinent to test the efficacy of a mucosally targeted vaccine formulation. The B subunit of the Vibrio cholerae cholera toxin (CTB) has great potential to act as a mucosal carrier for subunit vaccines. In the present study we evaluated whether a MUC1 tandem repeat (TR) peptide chemically linked to CTB would break self-antigen tolerance in the transgenic MUC1 tolerant mouse model (MUC1.Tg) through oral or parenteral immunizations. We report that oral immunization with the CTB-MUC1 conjugate along with mucosal adjuvant, unmethylated CpG oligodeoxynucleotide (ODN) and interleukin-12 (IL-12), did not break self-antigen tolerance in MUC1.Tg mice, but induced a strong humoral response in wild-type C57BL/6 mice. However, self-antigen tolerance in the MUC1.Tg mouse model was broken after parenteral immunizations with different doses of the CTB-MUC1 conjugate protein and with the adjuvant CpG ODN co-delivered with CTB-MUC1. Importantly, mice immunized systemically with CpG ODN alone and with CTB-MUC1 exhibited decreased tumor burden when challenged with a mammary gland tumor cell line that expresses human MUC1. PMID:20824430

  17. MUC1 intra-cellular trafficking is clathrin, dynamin, and rab5 dependent

    International Nuclear Information System (INIS)

    Liu Xiaolong; Yuan Zhenglong; Chung, Maureen

    2008-01-01

    MUC1, a transmembrane glycoprotein, is abnormally over-expressed in most human adenocarcinomas. MUC1 association with cytoplasmic cell signal regulators and nuclear accumulation are important for its tumor related activities. Little is known about how MUC1 translocates from the cell membrane to the cytoplasm. In this study, live cell imaging was used to study MUC1 intracellular trafficking. The interaction between EGFR and MUC1 was mapped by FRET analysis and EGF stimulated MUC1 endocytosis was observed directly through live cell imaging. MUC1-CT endocytosis was clathrin and dynamin dependent. Rab5 over-expression resulted in decreased cell membrane localization of MUC1, with accumulation of MUC1 endocytic vesicles in the peri-nuclear region. Conversely, over-expression of a Rab5 dominant negative mutant (S34N) resulted in redistribution of MUC1 from the peri-nuclear region to the cytoplasm. Collectively, these results indicated that MUC1 intra-cellular trafficking occurs through a regulated process that was stimulated by direct EGFR and MUC1 interaction, mediated by clathrin coated pits that were dynamin dependent and regulated by Rab5

  18. Novel MUC1 aptamer selectively delivers cytotoxic agent to cancer cells in vitro.

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    Yan Hu

    Full Text Available Chemotherapy is a primary treatment for cancer, but its efficacy is often limited by the adverse effects of cytotoxic agents. Targeted drug delivery may reduce the non-specific toxicity of chemotherapy by selectively directing anticancer drugs to tumor cells. MUC1 protein is an attractive target for tumor-specific drug delivery owning to its overexpression in most adenocarcinomas. In this study, a novel MUC1 aptamer is exploited as the targeting ligand for carrying doxorubicin (Dox to cancer cells. We developed an 86-base DNA aptamer (MA3 that bound to a peptide epitope of MUC1 with a K(d of 38.3 nM and minimal cross reactivity to albumin. Using A549 lung cancer and MCF-7 breast cancer cells as MUC1-expressing models, MA3 was found to preferentially bind to MUC1-positive but not MUC1-negative cells. An aptamer-doxorubicin complex (Apt-Dox was formulated by intercalating doxorubicin into the DNA structure of MA3. Apt-Dox was found capable of carrying doxorubicin into MUC1-positive tumor cells, while significantly reducing the drug intake by MUC1-negative cells. Moreover, Apt-Dox retained the efficacy of doxorubicin against MUC1-positive tumor cells, but lowered the toxicity to MUC1-negative cells (P<0.01. The results suggest that the MUC1 aptamer may have potential utility as a targeting ligand for selective delivery of cytotoxic agent to MUC1-expressing tumors.

  19. The MUC1 extracellular domain subunit is found in nuclear speckles and associates with spliceosomes.

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    Priyadarsini Kumar

    Full Text Available MUC1 is a large transmembrane glycoprotein and oncogene expressed by epithelial cells and overexpressed and underglycosylated in cancer cells. The MUC1 cytoplasmic subunit (MUC1-C can translocate to the nucleus and regulate gene expression. It is frequently assumed that the MUC1 extracellular subunit (MUC1-N does not enter the nucleus. Based on an unexpected observation that MUC1 extracellular domain antibody produced an apparently nucleus-associated staining pattern in trophoblasts, we have tested the hypothesis that MUC1-N is expressed inside the nucleus. Three different antibodies were used to identify MUC1-N in normal epithelial cells and tissues as well as in several cancer cell lines. The results of immunofluorescence and confocal microscopy analyses as well as subcellular fractionation, Western blotting, and siRNA/shRNA studies, confirm that MUC1-N is found within nuclei of all cell types examined. More detailed examination of its intranuclear distribution using a proximity ligation assay, subcellular fractionation, and immunoprecipitation suggests that MUC1-N is located in nuclear speckles (interchromatin granule clusters and closely associates with the spliceosome protein U2AF65. Nuclear localization of MUC1-N was abolished when cells were treated with RNase A and nuclear localization was altered when cells were incubated with the transcription inhibitor 5,6-dichloro-1-b-d-ribofuranosylbenzimidazole (DRB. While MUC1-N predominantly associated with speckles, MUC1-C was present in the nuclear matrix, nucleoli, and the nuclear periphery. In some nuclei, confocal microscopic analysis suggest that MUC1-C staining is located close to, but only partially overlaps, MUC1-N in speckles. However, only MUC1-N was found in isolated speckles by Western blotting. Also, MUC1-C and MUC1-N distributed differently during mitosis. These results suggest that MUC1-N translocates to the nucleus where it is expressed in nuclear speckles and that MUC1-N and MUC

  20. Molecular interactions between MUC1 epithelial mucin, β-catenin, and CagA proteins

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    Wei eGuang

    2012-05-01

    Full Text Available Interleukin (IL-8-driven neutrophil infiltration of the gastric mucosa is pathognomonic of persistent Helicobacter pylori infection. Our prior study showed that ectopic over-expression of MUC1 in human AGS gastric epithelial cells reduced H. pylori-stimulated IL-8 production compared with cells expressing MUC1 endogenously. Conversely, Muc1 knockout (Muc1-/- mice displayed an increased level of transcripts encoding the keratinocyte chemoattractant (KC, the murine equivalent of human IL-8, in gastric mucosa compared with Muc1(+/+ mice during experimental H. pylori infection. The current study tested the hypothesis that a decreased IL-8 level observed following MUC1 over-expression is mediated through the ability of MUC1 to associate with β-catenin, thereby inhibiting H. pylori-induced β-catenin nuclear translocation. Increased neutrophil infiltration of the gastric mucosa of H. pylori-infected Muc1(-/- mice was observed compared with Muc1(+/+ wild type littermates, thus defining the functional consequences of increased KC expression in the Muc1-null animals. Protein co-immunoprecipitation (coIP studies using lysates of untreated or H. pylori-treated AGS cells demonstrated that (a MUC1 formed a coIP complex with β-catenin and CagA, (b MUC1 over-expression reduced CagA/β-catenin coIP, and (c in the absence of MUC1 over-expression, H. pylori infection increased the nuclear level of β-catenin, (d whereas MUC1 over-expression decreased bacteria-driven β-catenin nuclear localization. These results suggest that manipulation of MUC1 expression in gastric epithelia may be an effective therapeutic strategy to inhibit H. pylori-dependent IL-8 production, neutrophil infiltration, and stomach inflammation.

  1. Flow cytometry-based assay to evaluate human serum MUC1-Tn antibodies

    DEFF Research Database (Denmark)

    Van Elssen, Catharina H M J; Clausen, Henrik; Germeraad, Wilfred T V

    2011-01-01

    Mucin-1 (MUC1) is a heavily O-glycosylated, transmembrane protein that is expressed on the apical surface of most secretory epithelia. In malignantly transformed epithelia, MUC1 has lost its apical distribution, is underglycosylated and is secreted into the circulation. Due to the underglycosylat......Mucin-1 (MUC1) is a heavily O-glycosylated, transmembrane protein that is expressed on the apical surface of most secretory epithelia. In malignantly transformed epithelia, MUC1 has lost its apical distribution, is underglycosylated and is secreted into the circulation. Due...... to detect antibodies binding to the underglycosylated MUC1 protein. This cellular system is complementary to the previously published methods to detect MUC1 serum antibodies, since the antibodies to the native protein are evaluated and therefore it can be effectively used for MUC1 antibody monitoring...... in vaccination studies as well as for functional assays....

  2. Distinguishing Truncated and Normal MUC1 Glycoform Targeting from Tn-MUC1-Specific CAR T Cells

    DEFF Research Database (Denmark)

    Posey, Avery D; Clausen, Henrik; June, Carl H

    2016-01-01

    Genetically modified T cells expressing chimeric antigen receptors (CARs) demonstrate potent clinical antitumor effects in a variety of blood cancers. However, clinical activity in solid tumors has been disappointing and toxicity has been a serious concern (Lamers et al., 2013; Morgan et al., 2010......). We recently found that a CAR composed of a scFv antibody fragment specific for the Tn-glycoform of MUC1 had potent activity in preclinical models of blood cancer and adenocarcinoma (Posey et al., 2016)....

  3. Complex of MUC1, CIN85 and Cbl in Colon Cancer Progression and Metastasis

    International Nuclear Information System (INIS)

    Cascio, Sandra; Finn, Olivera J.

    2015-01-01

    We previously reported that CIN85, an 85 KDa protein known to be involved in tumor cell migration and metastasis through its interaction with Cbl, associates with MUC1 in tumor cells. MUC1/CIN85 complex also regulates migration and invasion of tumor cells in vitro. Here, we examined specifically human colon carcinoma tissue microarrays (TMA) by immunohistochemistry for the expression of MUC1 and CIN85 and their potential role in cancer progression and metastasis. We detected a significant increase in expression of both MUC1 and CIN85 associated with advanced tumor stage and lymph node metastasis. We further investigated if Cbl could also be present in the MUC1/CIN85 complex. Co-immunoprecipitation assay showed that Cbl co-localized both with CIN85 and with MUC1 in a human colon cancer cell line. To begin to investigate the in vivo relevance of MUC1 overexpression and association with CIN85 and Cbl in cancer development and progression, we used human MUC1 transgenic mice that express MUC1 on the colonic epithelial cells, treated with azoxymethane to initiate and dextran sulfate sodium (AOM/DSS) to promote colorectal carcinogenesis. MUC1.Tg mice showed higher tumor incidence and decreased survival when compared with wild-type mice. Consistent with the in vitro data, the association of MUC1, CIN85 and Cbl was detected in colon tissues of AOM/DSS-treated MUC1 transgenic mice. MUC1/CIN85/Cbl complex appears to contribute to promotion and progression of colon cancer and thus increased expression of MUC1, CIN85 and Cbl in early stage colon cancer might be predictive of poor prognosis

  4. Complex of MUC1, CIN85 and Cbl in Colon Cancer Progression and Metastasis

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    Cascio, Sandra, E-mail: sac131@pitt.edu [Department of Immunology, University of Pittsburgh School of Medicine, E1040 Biomedical Science Tower, Pittsburgh, PA 15261 (United States); Fondazione Ri.Med, via Bandiera, Palermo 90133 (Italy); Finn, Olivera J., E-mail: sac131@pitt.edu [Department of Immunology, University of Pittsburgh School of Medicine, E1040 Biomedical Science Tower, Pittsburgh, PA 15261 (United States)

    2015-02-10

    We previously reported that CIN85, an 85 KDa protein known to be involved in tumor cell migration and metastasis through its interaction with Cbl, associates with MUC1 in tumor cells. MUC1/CIN85 complex also regulates migration and invasion of tumor cells in vitro. Here, we examined specifically human colon carcinoma tissue microarrays (TMA) by immunohistochemistry for the expression of MUC1 and CIN85 and their potential role in cancer progression and metastasis. We detected a significant increase in expression of both MUC1 and CIN85 associated with advanced tumor stage and lymph node metastasis. We further investigated if Cbl could also be present in the MUC1/CIN85 complex. Co-immunoprecipitation assay showed that Cbl co-localized both with CIN85 and with MUC1 in a human colon cancer cell line. To begin to investigate the in vivo relevance of MUC1 overexpression and association with CIN85 and Cbl in cancer development and progression, we used human MUC1 transgenic mice that express MUC1 on the colonic epithelial cells, treated with azoxymethane to initiate and dextran sulfate sodium (AOM/DSS) to promote colorectal carcinogenesis. MUC1.Tg mice showed higher tumor incidence and decreased survival when compared with wild-type mice. Consistent with the in vitro data, the association of MUC1, CIN85 and Cbl was detected in colon tissues of AOM/DSS-treated MUC1 transgenic mice. MUC1/CIN85/Cbl complex appears to contribute to promotion and progression of colon cancer and thus increased expression of MUC1, CIN85 and Cbl in early stage colon cancer might be predictive of poor prognosis.

  5. Targeting MUC1-C suppresses polycomb repressive complex 1 in multiple myeloma.

    Science.gov (United States)

    Tagde, Ashujit; Markert, Tahireh; Rajabi, Hasan; Hiraki, Masayuki; Alam, Maroof; Bouillez, Audrey; Avigan, David; Anderson, Kenneth; Kufe, Donald

    2017-09-19

    The polycomb repressive complex 1 (PRC1) includes the BMI1, RING1 and RING2 proteins. BMI1 is required for survival of multiple myeloma (MM) cells. The MUC1-C oncoprotein is aberrantly expressed by MM cells, activates MYC and is also necessary for MM cell survival. The present studies show that targeting MUC1-C with (i) stable and inducible silencing and CRISPR/Cas9 editing and (ii) the pharmacologic inhibitor GO-203, which blocks MUC1-C function, downregulates BMI1, RING1 and RING2 expression. The results demonstrate that MUC1-C drives BMI1 transcription by a MYC-dependent mechanism. MUC1-C thus promotes MYC occupancy on the BMI1 promoter and thereby activates BMI1 expression. We also show that the MUC1-C→MYC pathway induces RING2 expression. Moreover, in contrast to BMI1 and RING2, we found that MUC1-C drives RING1 by an NF-κB p65-dependent mechanism. Targeting MUC1-C and thereby the suppression of these key PRC1 proteins was associated with downregulation of the PRC1 E3 ligase activity as evidenced by decreases in ubiquitylation of histone H2A. Targeting MUC1-C also resulted in activation of the PRC1-repressed tumor suppressor genes, PTEN, CDNK2A and BIM . These findings identify a heretofore unrecognized role for MUC1-C in the epigenetic regulation of MM cells.

  6. Cooperative interaction of MUC1 with the HGF/c-Met pathway during hepatocarcinogenesis.

    Science.gov (United States)

    Bozkaya, Giray; Korhan, Peyda; Cokaklı, Murat; Erdal, Esra; Sağol, Ozgül; Karademir, Sedat; Korch, Christopher; Atabey, Neşe

    2012-09-11

    Hepatocyte growth factor (HGF) induced c-Met activation is known as the main stimulus for hepatocyte proliferation and is essential for liver development and regeneration. Activation of HGF/c-Met signaling has been correlated with aggressive phenotype and poor prognosis in hepatocellular carcinoma (HCC). MUC1 is a transmembrane mucin, whose over-expression is reported in most cancers. Many of the oncogenic effects of MUC1 are believed to occur through the interaction of MUC1 with signaling molecules. To clarify the role of MUC1 in HGF/c-Met signaling, we determined whether MUC1 and c-Met interact cooperatively and what their role(s) is in hepatocarcinogenesis. MUC1 and c-Met over-expression levels were determined in highly motile and invasive, mesenchymal-like HCC cell lines, and in serial sections of cirrhotic and HCC tissues, and these levels were compared to those in normal liver tissues. Co-expression of both c-Met and MUC1 was found to be associated with the differentiation status of HCC. We further demonstrated an interaction between c-Met and MUC1 in HCC cells. HGF-induced c-Met phosphorylation decreased this interaction, and down-regulated MUC1 expression. Inhibition of c-Met activation restored HGF-mediated MUC1 down-regulation, and decreased the migratory and invasive abilities of HCC cells via inhibition of β-catenin activation and c-Myc expression. In contrast, siRNA silencing of MUC1 increased HGF-induced c-Met activation and HGF-induced cell motility and invasion. These findings indicate that the crosstalk between MUC1 and c-Met in HCC could provide an advantage for invasion to HCC cells through the β-catenin/c-Myc pathway. Thus, MUC1 and c-Met could serve as potential therapeutic targets in HCC.

  7. MUC1 enhances invasiveness of pancreatic cancer cells by inducing epithelial to mesenchymal transition.

    Science.gov (United States)

    Roy, L D; Sahraei, M; Subramani, D B; Besmer, D; Nath, S; Tinder, T L; Bajaj, E; Shanmugam, K; Lee, Y Y; Hwang, S I L; Gendler, S J; Mukherjee, P

    2011-03-24

    Increased motility and invasiveness of pancreatic cancer cells are associated with epithelial to mesenchymal transition (EMT). Snai1 and Slug are zinc-finger transcription factors that trigger this process by repressing E-cadherin and enhancing vimentin and N-cadherin protein expression. However, the mechanisms that regulate this activation in pancreatic tumors remain elusive. MUC1, a transmembrane mucin glycoprotein, is associated with the most invasive forms of pancreatic ductal adenocarcinomas (PDA). In this study, we show that over expression of MUC1 in pancreatic cancer cells triggers the molecular process of EMT, which translates to increased invasiveness and metastasis. EMT was significantly reduced when MUC1 was genetically deleted in a mouse model of PDA or when all seven tyrosines in the cytoplasmic tail of MUC1 were mutated to phenylalanine (mutated MUC1 CT). Using proteomics, RT-PCR and western blotting, we revealed a significant increase in vimentin, Slug and Snail expression with repression of E-Cadherin in MUC1-expressing cells compared with cells expressing the mutated MUC1 CT. In the cells that carried the mutated MUC1 CT, MUC1 failed to co-immunoprecipitate with β-catenin and translocate to the nucleus, thereby blocking transcription of the genes associated with EMT and metastasis. Thus, functional tyrosines are critical in stimulating the interactions between MUC1 and β-catenin and their nuclear translocation to initiate the process of EMT. This study signifies the oncogenic role of MUC1 CT and is the first to identify a direct role of the MUC1 in initiating EMT during pancreatic cancer. The data may have implications in future design of MUC1-targeted therapies for pancreatic cancer.

  8. Cooperative interaction of MUC1 with the HGF/c-Met pathway during hepatocarcinogenesis

    Directory of Open Access Journals (Sweden)

    Bozkaya Giray

    2012-09-01

    Full Text Available Abstract Background Hepatocyte growth factor (HGF induced c-Met activation is known as the main stimulus for hepatocyte proliferation and is essential for liver development and regeneration. Activation of HGF/c-Met signaling has been correlated with aggressive phenotype and poor prognosis in hepatocellular carcinoma (HCC. MUC1 is a transmembrane mucin, whose over-expression is reported in most cancers. Many of the oncogenic effects of MUC1 are believed to occur through the interaction of MUC1 with signaling molecules. To clarify the role of MUC1 in HGF/c-Met signaling, we determined whether MUC1 and c-Met interact cooperatively and what their role(s is in hepatocarcinogenesis. Results MUC1 and c-Met over-expression levels were determined in highly motile and invasive, mesenchymal-like HCC cell lines, and in serial sections of cirrhotic and HCC tissues, and these levels were compared to those in normal liver tissues. Co-expression of both c-Met and MUC1 was found to be associated with the differentiation status of HCC. We further demonstrated an interaction between c-Met and MUC1 in HCC cells. HGF-induced c-Met phosphorylation decreased this interaction, and down-regulated MUC1 expression. Inhibition of c-Met activation restored HGF-mediated MUC1 down-regulation, and decreased the migratory and invasive abilities of HCC cells via inhibition of β-catenin activation and c-Myc expression. In contrast, siRNA silencing of MUC1 increased HGF-induced c-Met activation and HGF-induced cell motility and invasion. Conclusions These findings indicate that the crosstalk between MUC1 and c-Met in HCC could provide an advantage for invasion to HCC cells through the β-catenin/c-Myc pathway. Thus, MUC1 and c-Met could serve as potential therapeutic targets in HCC.

  9. Muc1 deficiency exacerbates pulmonary fibrosis in a mouse model of silicosis.

    Science.gov (United States)

    Kato, Kosuke; Zemskova, Marina A; Hanss, Alec D; Kim, Marianne M; Summer, Ross; Kim, Kwang Chul

    2017-11-25

    MUC1 (MUC in human and Muc in animals) is a membrane-tethered mucin expressed on the apical surface of lung epithelial cells. However, in the lungs of patients with interstitial lung disease, MUC1 is aberrantly expressed in hyperplastic alveolar type II epithelial (ATII) cells and alveolar macrophages (AM), and elevated levels of extracellular MUC1 are found in bronchoalveolar lavage (BAL) fluid and the serum of these patients. While pro-fibrotic effects of extracellular MUC1 have recently been described in cultured fibroblasts, the contribution of MUC1 to the pathobiology of pulmonary fibrosis is unknown. In this study, we hypothesized that MUC1 deficiency would reduce susceptibility to pulmonary fibrosis in a mouse model of silicosis. We employed human MUC1 transgenic mice, Muc1 deficient mice and wild-type mice on C57BL/6 background in these studies. Some mice received a one-time dose of crystalline silica instilled into their oropharynx in order to induce pulmonary fibrosis and assess the effects of Muc1 deficiency on fibrotic and inflammatory responses in the lung. As previously described in other mouse models of pulmonary fibrosis, we found that extracellular MUC1 levels were markedly increased in whole lung tissues, BALF and serum of human MUC1 transgenic mice after silica. We also detected an increase in total MUC1 levels in the lungs of these mice, indicating that production as well as release contributed to elevated levels after lung injury. Immunohistochemical staining revealed that increased MUC1 expression was mostly confined to ATII cells and AMs in areas of fibrotic remodeling, illustrating a pattern similar to the expression of MUC1 in human fibrotic lung tissues. However, contrary to our hypothesis, we found that Muc1 deficiency resulted in a worsening of fibrotic remodeling in the mouse lung as judged by an increase in number of silicotic nodules, an increase in lung collagen deposition and an increase in the severity of pulmonary inflammation

  10. Molecular mimics of the tumour antigen MUC1.

    Directory of Open Access Journals (Sweden)

    Tharappel C James

    Full Text Available A key requirement for the development of cancer immunotherapy is the identification of tumour-associated antigens that are differentially or exclusively expressed on the tumour and recognized by the host immune system. However, immune responses to such antigens are often muted or lacking due to the antigens being recognized as "self", and further complicated by the tumour environment and regulation of immune cells within. In an effort to circumvent the lack of immune responses to tumour antigens, we have devised a strategy to develop potential synthetic immunogens. The strategy, termed mirror image phage display, is based on the concept of molecular mimicry as demonstrated by the idiotype/anti-idiotype paradigm in the immune system. Here as 'proof of principle' we have selected molecular mimics of the well-characterised tumour associated antigen, the human mucin1 protein (MUC1 from two different peptide phage display libraries. The putative mimics were compared in structure and function to that of the native antigen. Our results demonstrate that several of the mimic peptides display T-cell stimulation activity in vitro when presented by matured dendritic cells. The mimic peptides and the native MUC1 antigenic epitopes can cross-stimulate T-cells. The data also indicate that sequence homology and/or chemical properties to the original epitope are not the sole determining factors for the observed immunostimulatory activity of the mimic peptides.

  11. Investigating MUC1/ICAM-1 Binding Induced Signaling in Breast Cancer Metastasis

    Science.gov (United States)

    2011-05-01

    at the molecular weight expected for a CD8/MUC1 dimer (Fig 4.9C). MUC1-CD contains SH2 and SH3 binding domains which act to recruit Src kinase To...recruitment of Src kinase , we assayed dimerization in MUC1-CFP-Fv cells with SH2 and/or SH3 domains mutated (Fig 4.11). As described below, MUC1-CFP-Fv...contains SH2 and SH3 binding domains for Src kinase . MUCI-CFP-Fv cells with mutations of the SH2 (Y46F; b.SH2) and/ or the putative Src SH3 binding

  12. MUC1-specific cytotoxic T lymphocytes eradicate tumors when adoptively transferred in vivo.

    Science.gov (United States)

    Mukherjee, P; Ginardi, A R; Tinder, T L; Sterner, C J; Gendler, S J

    2001-03-01

    We have reported previously that MUC1 transgenic mice with spontaneous tumors of the pancreas (designated MET) naturally develop MHC class I-restricted, MUC1-specific CTLs as tumors progress (P. Mukherjee et al., J. Immunol., 165: 3451-3460, 2000). From these MET mice, we have isolated, expanded, and cloned naturally occurring MUC1-specific CTLs in vitro. In this report, we show that the CTL line is predominantly CD8+ T cells and expresses T-cell receptor Vbeta chains 5.1/5.2, 11, 13, and 2 and Valpha chains 2, 8.3, 3.2, and 11.1/11.2. These CTLs recognize several epitopes on the MUC1 tandem repeat with highest affinity to APGSTAPPA. The CTL clone, on the other hand, is 100% CD8+ cells and expresses a single Vbeta chain of 5.1/5.2 and Valpha2. It recognizes only the H-2Db class I-restricted epitope of MUC1, APGSTAPPA. When adoptively transferred, the CTLs were effective in eradicating MUC1-expressing injected tumor cells including mammary gland cells (C57mg) and B16 melanomas. These results suggest that MUC1-specific CTLs are capable of possibly preventing, or at least substantially delaying, MUC1-expressing tumor formation. To our knowledge, this is the first evidence that demonstrates that the naturally occurring MUC1-specific CTLs isolated from one tumor model has antitumor effects on other MUC1-expressing tumors in vivo. Therefore, our data confirm that MUC1 is an important tumor rejection antigen and can serve as a target for immunotherapy.

  13. MUC1 selectively targets human pancreatic cancer in orthotopic nude mouse models.

    Directory of Open Access Journals (Sweden)

    Jeong Youp Park

    Full Text Available The goal of this study was to determine whether MUC1 antibody conjugated with a fluorophore could be used to visualize pancreatic cancer. Anti-MUC1 (CT2 antibody was conjugated with 550 nm or 650 nm fluorophores. Nude mouse were used to make subcutaneous and orthotopic models of pancreatic cancer. Western blot and flow cytometric analysis confirmed the expression of MUC1 in human pancreatic cancer cell lines including BxPC-3 and Panc-1. Immunocytochemistry with fluorophore conjugated anti-MUC1 antibody demonstrated fluorescent areas on the membrane of Panc-1 cancer cells. After injecting the conjugated anti-MUC1 antibodies via the tail vein, subcutaneously transplanted Panc-1 and BxPC-3 tumors emitted strong fluorescent signals. In the subcutaneous tumor models, the fluorescent signal from the conjugated anti-MUC1 antibody was noted around the margin of the tumor and space between the cells. The conjugated anti-MUC1 antibody bound the tumor in orthotopically-transplanted Panc-1 and BxPC-3 models enabling the tumors to be imaged. This study showed that fluorophore conjugated anti-MUC1 antibodies could visualize pancreatic tumors in vitro and in vivo and may help to improve the diagnosis and treatment of pancreatic cancer.

  14. MUC1-C activates polycomb repressive complexes and downregulates tumor suppressor genes in human cancer cells.

    Science.gov (United States)

    Rajabi, Hasan; Hiraki, Masayuki; Kufe, Donald

    2018-04-01

    The PRC2 and PRC1 complexes are aberrantly expressed in human cancers and have been linked to decreases in patient survival. MUC1-C is an oncoprotein that is also overexpressed in diverse human cancers and is associated with a poor prognosis. Recent studies have supported a previously unreported function for MUC1-C in activating PRC2 and PRC1 in cancer cells. In the regulation of PRC2, MUC1-C (i) drives transcription of the EZH2 gene, (ii) binds directly to EZH2, and (iii) enhances occupancy of EZH2 on target gene promoters with an increase in H3K27 trimethylation. Regarding PRC1, which is recruited to PRC2 sites in the hierarchical model, MUC1-C induces BMI1 transcription, forms a complex with BMI1, and promotes H2A ubiquitylation. MUC1-C thereby contributes to the integration of PRC2 and PRC1-mediated repression of tumor suppressor genes, such as CDH1, CDKN2A, PTEN and BRCA1. Like PRC2 and PRC1, MUC1-C is associated with the epithelial-mesenchymal transition (EMT) program, cancer stem cell (CSC) state, and acquisition of anticancer drug resistance. In concert with these observations, targeting MUC1-C downregulates EZH2 and BMI1, inhibits EMT and the CSC state, and reverses drug resistance. These findings emphasize the significance of MUC1-C as a therapeutic target for inhibiting aberrant PRC function and reprogramming the epigenome in human cancers.

  15. MUC1-C Represses the Crumbs Complex Polarity Factor CRB3 and Downregulates the Hippo Pathway

    Science.gov (United States)

    Alam, Maroof; Bouillez, Audrey; Tagde, Ashujit; Ahmad, Rehan; Rajabi, Hasan; Maeda, Takahiro; Hiraki, Masayuki; Suzuki, Yozo; Kufe, Donald

    2016-01-01

    Apical-basal polarity and epithelial integrity are maintained in part by the Crumbs (CRB) complex. The C-terminal subunit of MUC1 (MUC1-C) is a transmembrane protein that is expressed at the apical border of normal epithelial cells and aberrantly at high levels over the entire surface of their transformed counterparts. However, it is not known if MUC1-C contributes to this loss of polarity that is characteristic of carcinoma cells. Here it is demonstrated that MUC1-C downregulates expression of the Crumbs complex CRB3 protein in triple-negative breast cancer (TNBC) cells. MUC1-C associates with ZEB1 on the CRB3 promoter and represses CRB3 transcription. Notably, CRB3 activates the core kinase cassette of the Hippo pathway, which includes LATS1 and LATS2. In this context, targeting MUC1-C was associated with increased phosphorylation of LATS1, consistent with activation of the Hippo pathway, which is critical for regulating cell contact, tissue repair, proliferation and apoptosis. Also shown is that MUC1-C-mediated suppression of CRB3 and the Hippo pathway is associated with dephosphorylation and activation of the oncogenic YAP protein. In turn, MUC1-C interacts with YAP, promotes formation of YAP/β-catenin complexes and induces the WNT target gene MYC. These data support a previously unrecognized model in which targeting MUC1-C in TNBC cells (i) induces CRB3 expression, (ii) activates the CRB3-driven Hippo pathway, (iii) inactivates YAP, and thereby (iv) suppresses YAP/β-catenin-mediated induction of MYC expression. Implications These findings demonstrate a previously unrecognized role for the MUC1-C oncoprotein in the regulation of polarity and the Hippo pathway in breast cancer. PMID:27658423

  16. MUC1-C activates EZH2 expression and function in human cancer cells.

    Science.gov (United States)

    Rajabi, Hasan; Hiraki, Masayuki; Tagde, Ashujit; Alam, Maroof; Bouillez, Audrey; Christensen, Camilla L; Samur, Mehmet; Wong, Kwok-Kin; Kufe, Donald

    2017-08-07

    The EZH2 histone methyltransferase is a member of the polycomb repressive complex 2 (PRC2) that is highly expressed in diverse human cancers and is associated with a poor prognosis. MUC1-C is an oncoprotein that is similarly overexpressed in carcinomas and has been linked to epigenetic regulation. A role for MUC1-C in regulating EZH2 and histone methylation is not known. Here, we demonstrate that targeting MUC1-C in diverse human carcinoma cells downregulates EZH2 and other PRC2 components. MUC1-C activates (i) the EZH2 promoter through induction of the pRB→E2F pathway, and (ii) an NF-κB p65 driven enhancer in exon 1. We also show that MUC1-C binds directly to the EZH2 CXC region adjacent to the catalytic SET domain and associates with EZH2 on the CDH1 and BRCA1 promoters. In concert with these results, targeting MUC1-C downregulates EZH2 function as evidenced by (i) global and promoter-specific decreases in H3K27 trimethylation (H3K27me3), and (ii) activation of tumor suppressor genes, including BRCA1. These findings highlight a previously unreported role for MUC1-C in activating EZH2 expression and function in cancer cells.

  17. Glycopeptide dendrimers. Part II

    Czech Academy of Sciences Publication Activity Database

    Niederhafner, Petr; Šebestík, Jaroslav; Ježek, Jan

    2008-01-01

    Roč. 14, č. 1 (2008), s. 44-65 ISSN 1075-2617 R&D Projects: GA ČR GA203/03/1362; GA ČR GA203/06/1272; GA MZe QF3115; GA AV ČR KAN200520703 Institutional research plan: CEZ:AV0Z40550506 Keywords : artificial virus * cascade-release dendrimers * glycopeptide dendrimers * glycoconjugate * glycopeptides Subject RIV: CC - Organic Chemistry Impact factor: 1.654, year: 2008

  18. MUC-1-ESA+ progenitor cells in normal benign and malignant human breast epithelial cells

    OpenAIRE

    Lu, Xinquan; Li, Huixiang; Xu, Kejia; Nesland, Jahn M.; Suo, Zhenhe

    2009-01-01

    The existence of mammary epithelial stem/progenitor cells has been demonstrated in MUC-1-/ ESA+ subpopulations of breast epithelial cells. However, knowledge about the expression and localization in benign and malignant breast lesions is unknown. Using a double-staining immunohistochemistry method, we investigated MUC-1-/ESA+ cells in 10 normal breast tissues, 49 cases with fibrocystic disease, 40 fibroadenomas, 36 invasive ductal carcinomas and the breast cancer ce...

  19. Muc1 based breast cancer vaccines: role of post translational modifications

    International Nuclear Information System (INIS)

    Begum, M.; Khurshid, R.; Nagra, S.A.

    2008-01-01

    Vaccine development is one of the most promising fields in cancer research. After autologous transplantation, due to low tumour burden, patients are more likely to respond immunologically to a cancer vaccine. MUC1 with its adhesive and anti adhesive functions, immunostimulatory and immunosuppressive activities, is therefore a good candidate for breast cancer vaccine. A structure-based insight into the immunogenicity of natural MUC1 glyco forms, of its sub-domains, motifs and post translational modification like glycosylation and myriostoylation may aid the design of tumour vaccines. Primary sequences of human MUC1 were retrieved from the SWISSPROT data bank. Protein pattern search: The primary sequence of Human MUC1 was searched at PROSITE (a dictionary of protein sites and patterns) database. Our study observes that post-translational modifications play an important role in presenting MUC1 as a candidate for breast cancer vaccine. It is found that the phosphorylation and glycosylation of important functional motifs of MUC1 may take part in the production of cytokines that may provide immunization. (author)

  20. Glycopeptide antibiotic biosynthesis.

    Science.gov (United States)

    Yim, Grace; Thaker, Maulik N; Koteva, Kalinka; Wright, Gerard

    2014-01-01

    Glycopeptides such as vancomycin, teicoplanin and telavancin are essential for treating infections caused by Gram-positive bacteria. Unfortunately, the dwindled pipeline of new antibiotics into the market and the emergence of glycopeptide-resistant enterococci and other resistant bacteria are increasingly making effective antibiotic treatment difficult. We have now learned a great deal about how bacteria produce antibiotics. This information can be exploited to develop the next generation of antimicrobials. The biosynthesis of glycopeptides via nonribosomal peptide assembly and unusual amino acid synthesis, crosslinking and tailoring enzymes gives rise to intricate chemical structures that target the bacterial cell wall. This review seeks to describe recent advances in our understanding of both biosynthesis and resistance of these important antibiotics.

  1. Mucin 1 (MUC1 is a novel partner for MAL2 in breast carcinoma cells

    Directory of Open Access Journals (Sweden)

    McGuckin Michael A

    2009-01-01

    Full Text Available Abstract Background The MAL2 gene, encoding a four-transmembrane protein of the MAL family, is amplified and overexpressed in breast and other cancers, yet the significance of this is unknown. MAL-like proteins have trafficking functions, but their molecular roles are largely obscure, partly due to a lack of known binding partners. Methods Yeast two-hybrid screening of a breast carcinoma cDNA expression library was performed using a full-length MAL2 bait, and subsequent deletion mapping experiments were performed. MAL2 interactions were confirmed by co-immunoprecipitation analyses and confocal microscopy was employed to compare protein sub-cellular distributions. Sucrose density gradient centrifugation of membranes extracted in cold Triton X-100 was employed to compare protein distributions between Triton X-100-soluble and -insoluble fractions. Results The tumor-associated protein mucin 1 (MUC1 was identified as a potential MAL2 partner, with MAL2/MUC1 interactions being confirmed in myc-tagged MAL2-expressing MCF-10A cells using co-immunoprecipitation assays. Deletion mapping experiments demonstrated a requirement for the first MAL2 transmembrane domain for MUC1 binding, whereas the MAL2 N-terminal domain was required to bind D52-like proteins. Confocal microscopy identified cytoplasmic co-localisation of MUC1 and MAL2 in breast cell lines, and centrifugation of cell lysates to equilibrium in sucrose density gradients demonstrated that MAL2 and MUC1 proteins were co-distributed between Triton X-100-soluble and -insoluble fractions. However co-immunoprecipitation analyses detected MAL2/MUC1 interactions in Triton X-100-soluble fractions only. Myc-MAL2 expression in MCF-10A cells was associated with both increased MUC1 detection within Triton X-100-soluble and -insoluble fractions, and increased MUC1 detection at the cell surface. Conclusion These results identify MUC1 as a novel MAL2 partner, and suggest a role for MAL2 in regulating MUC1

  2. No evidence of association of MUC-1 genetic polymorphism with embryo implantation failure

    Directory of Open Access Journals (Sweden)

    D.B. Dentillo

    2007-06-01

    Full Text Available Pregnancy loss can be caused by several factors involved in human reproduction. Although up to 50% of cases remain unexplained, it has been postulated that the major cause of failed pregnancy is an error of embryo implantation. Transmembrane mucin-1 (MUC-1 is a glycoprotein expressed on the endometrial cell surface which acts as a barrier to implantation. The gene that codes for this molecule is composed of a polymorphic tandem repeat of 60 nucleotides. Our objective was to determine if MUC-1 genetic polymorphism is associated with implantation failure in patients with a history of recurrent abortion. The study was conducted on 10 women aged 25 to 35 years with no history of successful pregnancy and with a diagnosis of infertility. The control group consisted of 32 patients aged 25 to 35 years who had delivered at least two full-term live children and who had no history of abortions or fetal losses. MUC-1 amplicons were obtained by PCR and observed on agarose and polyacrylamide gel after electrophoresis. Statistical analysis showed no significant difference in the number of MUC-1 variable number of tandem repeats between these groups (P > 0.05. Our results suggest that there is no effect of the polymorphic MUC-1 sequence on the implantation failure. However, the data do not exclude MUC-1 relevance during embryo implantation. The process is related to several associated factors such as the mechanisms of gene expression in the uterus, specific MUC-1 post-translational modifications and appropriate interactions with other molecules during embryo implantation.

  3. Targeting MUC1-C suppresses BCL2A1 in triple-negative breast cancer.

    Science.gov (United States)

    Hiraki, Masayuki; Maeda, Takahiro; Mehrotra, Neha; Jin, Caining; Alam, Maroof; Bouillez, Audrey; Hata, Tsuyoshi; Tagde, Ashujit; Keating, Amy; Kharbanda, Surender; Singh, Harpal; Kufe, Donald

    2018-01-01

    B-cell lymphoma 2-related protein A1 (BCL2A1) is a member of the BCL-2 family of anti-apoptotic proteins that confers resistance to treatment with anti-cancer drugs; however, there are presently no agents that target BCL2A1. The MUC1-C oncoprotein is aberrantly expressed in triple-negative breast cancer (TNBC) cells, induces the epithelial-mesenchymal transition (EMT) and promotes anti-cancer drug resistance. The present study demonstrates that targeting MUC1-C genetically and pharmacologically in TNBC cells results in the downregulation of BCL2A1 expression. The results show that MUC1-C activates the BCL2A1 gene by an NF-κB p65-mediated mechanism, linking this pathway with the induction of EMT. The MCL-1 anti-apoptotic protein is also of importance for the survival of TNBC cells and is an attractive target for drug development. We found that inhibiting MCL-1 with the highly specific MS1 peptide results in the activation of the MUC1-C→NF-κB→BCL2A1 pathway. In addition, selection of TNBC cells for resistance to ABT-737, which inhibits BCL-2, BCL-xL and BCL-W but not MCL-1 or BCL2A1, is associated with the upregulation of MUC1-C and BCL2A1 expression. Targeting MUC1-C in ABT-737-resistant TNBC cells suppresses BCL2A1 and induces death, which is of potential therapeutic importance. These findings indicate that MUC1-C is a target for the treatment of TNBCs unresponsive to agents that inhibit anti-apoptotic members of the BCL-2 family.

  4. Lectin Domains of Polypeptide GalNAc Transferases Exhibit Glycopeptide Binding Specificity

    DEFF Research Database (Denmark)

    Pedersen, Johannes W; Bennett, Eric P; Schjoldager, Katrine T-B G

    2011-01-01

    UDP-GalNAc:polypeptide a-N-acetylgalactosaminyltransferases (GalNAc-Ts) constitute a family of up to 20 transferases that initiate mucin-type O-glycosylation. The transferases are structurally composed of catalytic and lectin domains. Two modes have been identified for the selection...... of glycosylation sites by GalNAc-Ts: confined sequence recognition by the catalytic domain alone, and concerted recognition of acceptor sites and adjacent GalNAc-glycosylated sites by the catalytic and lectin domains, respectively. Thus far, only the catalytic domain has been shown to have peptide sequence...... on sequences of mucins MUC1, MUC2, MUC4, MUC5AC, MUC6, and MUC7 as well as a random glycopeptide bead library, we examined the binding properties of four different lectin domains. The lectin domains of GalNAc-T1, -T2, -T3, and -T4 bound different subsets of small glycopeptides. These results indicate...

  5. MUC1-C Oncoprotein Integrates a Program of EMT, Epigenetic Reprogramming and Immune Evasion in Human Carcinomas.

    Science.gov (United States)

    Rajabi, Hasan; Kufe, Donald

    2017-08-01

    The MUC1 gene evolved in mammalian species to provide protection of epithelia. The transmembrane MUC1 C-terminal subunit (MUC1-C) signals stress to the interior of the epithelial cell and, when overexpressed as in most carcinomas, functions as an oncoprotein. MUC1-C induces the epithelial-mesenchymal transition (EMT) by activating the inflammatory NF-κB p65 pathway and, in turn, the EMT-transcriptional repressor ZEB1. Emerging evidence has indicated that MUC1-C drives a program integrating the induction of EMT with activation of stem cell traits, epigenetic reprogramming and immune evasion. This mini-review focuses on the potential importance of this MUC1-C program in cancer progression. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Co-expression of HER3 and MUC1 is associated with a favourable prognosis in patients with bladder cancer

    DEFF Research Database (Denmark)

    Nielsen, Trine O; Borre, Michael; Nexo, Ebba

    2015-01-01

    OBJECTIVES: To investigate the functional impact of the interaction of MUC1 with the epidermal growth factor receptors HER3 and HER4 in patients with bladder cancer. PATIENTS AND METHODS: Using reverse transcription quantitative polymerase chain reaction, we examined MUC1 expression in 82 bladder...... the prognostic value of MUC1 (P = 0.488). MUC1 expression had no correlation with survival, tumour stage or grade, or to the prognostic value of HER4. CONCLUSIONS: A high MUC1 expression was associated with a favourable prognosis in patients with bladder cancer when the expression of HER3 was also high....... This suggests an involvement of HER3 in MUC1 function in bladder cancer....

  7. A soluble form of Siglec-9 provides an antitumor benefit against mammary tumor cells expressing MUC1 in transgenic mice

    Energy Technology Data Exchange (ETDEWEB)

    Tomioka, Yukiko, E-mail: ytomi@muses.tottori-u.ac.jp [Division of Disease Model Innovation, Institute for Genetic Medicine, Hokkaido University, Sapporo 060-0815 (Japan); Avian Zoonosis Research Center, Faculty of Agriculture, Tottori University, Tottori 680-8553 (Japan); Morimatsu, Masami, E-mail: mmorimat@vetmed.hokudai.ac.jp [Division of Disease Model Innovation, Institute for Genetic Medicine, Hokkaido University, Sapporo 060-0815 (Japan); Laboratory of Laboratory Animal Science and Medicine, Department of Disease Control, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo 060-0818 (Japan); Nishijima, Ken-ichi, E-mail: nishijma@nubio.nagoya-u.ac.jp [Department of Biotechnology, Graduate School of Engineering, Nagoya University, Nagoya 464-8603 (Japan); Usui, Tatsufumi, E-mail: usutatsu@muses.tottori-u.ac.jp [Avian Zoonosis Research Center, Faculty of Agriculture, Tottori University, Tottori 680-8553 (Japan); Yamamoto, Sayo, E-mail: ysayo@anim.med.kyushu-u.ac.jp [Center of Biomedical Research, Research Center for Human Disease Modeling, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582 (Japan); Suyama, Haruka, E-mail: sharuka@anim.med.kyushu-u.ac.jp [Center of Biomedical Research, Research Center for Human Disease Modeling, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582 (Japan); Ozaki, Kinuyo, E-mail: k-ozaki@anim.med.kyushu-u.ac.jp [Center of Biomedical Research, Research Center for Human Disease Modeling, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582 (Japan); Ito, Toshihiro, E-mail: toshiito@muses.tottori-u.ac.jp [Avian Zoonosis Research Center, Faculty of Agriculture, Tottori University, Tottori 680-8553 (Japan); and others

    2014-07-18

    Highlights: • Tumor-associated antigen MUC1 binds to Siglec-9. • Soluble Siglec-9 reduced proliferation of MUC1-positive tumor in transgenic mice. • Soluble Siglec-9 and MUC1 on tumor cells were colocalized in transgenic mice. • MUC1 expression on tumor cells were reduced in soluble Siglec-9 transgenic mice. - Abstract: Tumor-associated MUC1 binds to Siglec-9, which is expected to mediate tumor cell growth and negative immunomodulation. We hypothesized that a soluble form of Siglec-9 (sSiglec-9) competitively inhibits a binding of MUC1 to its receptor molecules like human Siglec-9, leading to provide antitumor benefit against MUC1-expressing tumor, and generated transgenic mouse lines expressing sSiglec-9 (sSiglec-9 Tg). When mammary tumor cells expressing MUC1 were intraperitoneally transplanted into sSiglec-9 Tg, tumor proliferation was slower with the lower histological malignancy as compared with non-transgenic mice. The sSiglec-9 was detected in the ascites caused by the tumor in the sSiglec-9 Tg, and sSiglec-9 and MUC1 were often colocalized on surfaces of the tumor cells. PCNA immunohistochemistry also revealed the reduced proliferation of the tumor cells in sSiglec-9 Tg. In sSiglec-9 Tg with remarkable suppression of tumor proliferation, MUC1 expressions were tend to be reduced. In the ascites of sSiglec-9 Tg bearing the tumor, T cells were uniformly infiltrated, whereas aggregations of degenerative T cells were often observed in the non-transgenic mice. These results suggest that sSiglec-9 has an antitumor benefit against MUC1-expressing tumor in the transgenic mice, which may avoid the negative immunomodulation and/or suppress tumor-associated MUC1 downstream signal transduction, and subsequent tumor proliferation.

  8. A soluble form of Siglec-9 provides an antitumor benefit against mammary tumor cells expressing MUC1 in transgenic mice

    International Nuclear Information System (INIS)

    Tomioka, Yukiko; Morimatsu, Masami; Nishijima, Ken-ichi; Usui, Tatsufumi; Yamamoto, Sayo; Suyama, Haruka; Ozaki, Kinuyo; Ito, Toshihiro

    2014-01-01

    Highlights: • Tumor-associated antigen MUC1 binds to Siglec-9. • Soluble Siglec-9 reduced proliferation of MUC1-positive tumor in transgenic mice. • Soluble Siglec-9 and MUC1 on tumor cells were colocalized in transgenic mice. • MUC1 expression on tumor cells were reduced in soluble Siglec-9 transgenic mice. - Abstract: Tumor-associated MUC1 binds to Siglec-9, which is expected to mediate tumor cell growth and negative immunomodulation. We hypothesized that a soluble form of Siglec-9 (sSiglec-9) competitively inhibits a binding of MUC1 to its receptor molecules like human Siglec-9, leading to provide antitumor benefit against MUC1-expressing tumor, and generated transgenic mouse lines expressing sSiglec-9 (sSiglec-9 Tg). When mammary tumor cells expressing MUC1 were intraperitoneally transplanted into sSiglec-9 Tg, tumor proliferation was slower with the lower histological malignancy as compared with non-transgenic mice. The sSiglec-9 was detected in the ascites caused by the tumor in the sSiglec-9 Tg, and sSiglec-9 and MUC1 were often colocalized on surfaces of the tumor cells. PCNA immunohistochemistry also revealed the reduced proliferation of the tumor cells in sSiglec-9 Tg. In sSiglec-9 Tg with remarkable suppression of tumor proliferation, MUC1 expressions were tend to be reduced. In the ascites of sSiglec-9 Tg bearing the tumor, T cells were uniformly infiltrated, whereas aggregations of degenerative T cells were often observed in the non-transgenic mice. These results suggest that sSiglec-9 has an antitumor benefit against MUC1-expressing tumor in the transgenic mice, which may avoid the negative immunomodulation and/or suppress tumor-associated MUC1 downstream signal transduction, and subsequent tumor proliferation

  9. MUC1 enhances tumor progression and contributes toward immunosuppression in a mouse model of spontaneous pancreatic adenocarcinoma.

    Science.gov (United States)

    Tinder, Teresa L; Subramani, Durai B; Basu, Gargi D; Bradley, Judy M; Schettini, Jorge; Million, Arefayene; Skaar, Todd; Mukherjee, Pinku

    2008-09-01

    MUC1, a membrane tethered mucin glycoprotein, is overexpressed and aberrantly glycosylated in >80% of human ductal pancreatic adenocarcinoma. However, the role of MUC1 in pancreatic cancer has been elusive, partly due to the lack of an appropriate model. We report the characterization of a novel mouse model that expresses human MUC1 as a self molecule (PDA.MUC1 mice). Pancreatic tumors arise in an appropriate MUC1-tolerant background within an immune-competent host. Significant enhancement in the development of pancreatic intraepithelial preneoplastic lesions and progression to adenocarcinoma is observed in PDA.MUC1 mice, possibly due to increased proliferation. Tumors from PDA.MUC1 mice express higher levels of cyclooxygenase-2 and IDO compared with PDA mice lacking MUC1, especially during early stages of tumor development. The increased proinflammatory milieu correlates with an increased percentage of regulatory T cells and myeloid suppressor cells in the pancreatic tumor and tumor draining lymph nodes. Data shows that during pancreatic cancer progression, MUC1-mediated mechanisms enhance the onset and progression of the disease, which in turn regulate the immune responses. Thus, the mouse model is ideally suited for testing novel chemopreventive and therapeutic strategies against pancreatic cancer.

  10. MUC1 enhances tumor progression and contributes towards immunosuppression in a mouse model of spontaneous pancreatic adenocarcinoma

    Science.gov (United States)

    Tinder, Teresa L.; Subramani, Durai B.; Basu, Gargi D.; Bradley, Judy M.; Schettini, Jorge; Million, Arefayene; Skaar, Todd

    2008-01-01

    MUC1, a membrane tethered mucin glycoprotein, is overexpressed and aberrantly glycosylated in >80% of human ductal pancreatic adenocarcinoma. However, the role of MUC1 in pancreatic cancer has been elusive, partly due to the lack of an appropriate model. We report the characterization of a novel mouse model that expresses human MUC1 as a self molecule (PDA.MUC1 mice). Pancreatic tumors arise in an appropriate MUC1-tolerant background within an immune competent host. Significant enhancement in the development of pancreatic intraepithelial pre-neoplastic lesions (PanINs) and progression to adenocarcinoma is observed in PDA.MUC1 mice, possibly due to increased proliferation. Tumors from PDA.MUC1 mice express higher levels of cyclooxygenase-2 and indoleamine 2,3, dioxygenase compared to PDA mice lacking MUC1, especially during early stages of tumor development. The increased pro-inflammatory milieu correlates with an increased percentage of regulatory T cells and myeloid suppressor cells in the pancreatic tumor and tumor draining lymph nodes. Data shows that during pancreatic cancer progression, MUC1-mediated mechanisms enhance the onset and progression of the disease which in turn regulate the immune responses. Thus, the mouse model is ideally-suited for testing novel chemopreventive and therapeutic strategies against pancreatic cancer. PMID:18713982

  11. Glycopeptide dendrimers. Part I

    Czech Academy of Sciences Publication Activity Database

    Niederhafner, Petr; Šebestík, Jaroslav; Ježek, Jan

    2008-01-01

    Roč. 14, č. 1 (2008), s. 2-43 ISSN 1075-2617 R&D Projects: GA ČR GA203/03/1362; GA ČR GA203/06/1272; GA MZe QF3115; GA AV ČR KAN200520703 Institutional research plan: CEZ:AV0Z40550506 Keywords : artificial virus * calixarene dendrimers * carbopeptide dendrimers * glycopeptide dendrimers Subject RIV: CC - Organic Chemistry Impact factor: 1.654, year: 2008

  12. Targeting of the MUC1-C Oncoprotein in Colitis-Associated Colorectal Cancer

    Science.gov (United States)

    2014-11-01

    separated by infiltrates of inflammatory cells and the presence of crypt abscess (lower left panel). With progression to dysplasia, the crypts are...Rajabi, H, et al., MUC1-C oncoprotein induces TCF7L2 activation and promotes cyclin D1 expression in human breast cancer cells. J Biol Chem, 2012

  13. Relationships between oral MUC1 expression and salivary hormones in burning mouth syndrome.

    Science.gov (United States)

    Kang, Jeong-Hyun; Kim, Yoon-Young; Chang, Ji-Youn; Kho, Hong-Seop

    2017-06-01

    To investigate possible relationships among oral mucosal epithelial MUC1 expression, salivary female gonadal hormones and stress markers, and clinical characteristics in patients with burning mouth syndrome (BMS). Thirty post-menopausal female patients with BMS (60.0±5.0 years) were included. Clinical and psychological evaluations were performed and the expression level of oral mucosal epithelial MUC1 was analyzed. The levels of cortisol, dehydroepiandrosterone (DHEA), 17β-estradiol, progesterone, chromogranin A, and blood contamination were determined from unstimulated whole saliva (UWS) and stimulated whole saliva (SWS) samples. Salivary progesterone level had significant positive correlations with oral mucosal epithelial MUC1 expression level and with salivary cortisol and DHEA levels. The salivary level of 17β-estradiol showed significant positive correlations with period of symptom duration, severity of effects of oral complaints on daily life, and results from psychological evaluations. Cortisol level in UWS and cortisol/DHEA ratio in UWS and SWS had negative correlations with severity of oral burning sensation significantly. The severity of taste disturbance had positive correlations with results from psychometry significantly. Dysregulated psychoendocrinological interactions might affect oral mucosal MUC1 expression and severity of oral burning sensation in post-menopausal BMS patients. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Electrochemical Sandwich Immunoassay for the Ultrasensitive Detection of Human MUC1 Cancer Biomarker

    Directory of Open Access Journals (Sweden)

    Zahra Taleat

    2013-01-01

    Full Text Available A new electrochemical sandwich immunoassay for the ultrasensitive detection of human MUC1 cancer biomarker using protein G-functionalized magnetic beads (MBs and graphite-based screen-printed electrodes (SPEs was developed. Magnetic beads were employed as the platforms for the immobilization and immunoreaction process. A pair of primary and secondary antibodies was used to capture the MUC1 protein. After labeling with a third antibody conjugated with horseradish peroxidase (HRP, the resulting conjugate was trapped at the surface of the graphite-based SPEs and MUC1 determination was carried out by differential pulse voltammetry (DPV at 0.4 V upon H2O2 addition using acetaminophen (APAP as the redox mediator. A linear relationship was obtained for the detection of human MUC1 over a range of 0–25 ppb with the lowest detection limit of 1.34 ppb when HRP was applied as a label. Preliminary experiments were performed using disposable electrochemical sensors in order to optimize some parameters (i.e., incubation times, concentrations, and blocking agent.

  15. Decreased expression of MUC1 induces apoptosis and inhibits migration in pancreatic cancer PANC-1 cells via regulation of Slug pathway.

    Science.gov (United States)

    Zhao, Ping; Meng, Meng; Xu, Bin; Dong, Aiping; Ni, Guangzhen; Lu, Lianfang

    2017-12-06

    MUC1, a membrane tethered mucin glycoprotein, is overexpressed in > 60% of human pancreatic cancers (PCs), and is associated with poor prognosis and enhanced metastasis. Here, we report the effect of silencing MUC1 expression on the growth, migration and invasive ability of pancreatic cancer cells, and explored its mechanisms. We observed that siRNA mediated suppression of the MUC1 expression significantly reduced invasive and migrative capability and induced apoptosis of the pancreatic cancer PANC-1 cells. We found that Slug was inhibited in the MUC1 siRNA transfected PANC-1 cells (MUC1 siRNA/PANC-1 cells). Expression of PUMA and E-cadherin was increased in the MUC1 siRNA/PANC-1 cells. PANC-1 cells overexpressing full long Slug gene (when transfected with Slug cDNA plasmid) significantly inhibited PUMA and E-cadherin expression in the MUC1 siRNA/PANC-1 cells. Silencing PUMA expression inhibited apoptosis in the MUC1 siRNA transfected PANC-1 cells (MUC1 siRNA/PANC-1 cells). Silencing E-cadherin expression restored the invasion and migration ability in the MUC1 siRNA/PANC-1 cells. We therefore concluded that silencing MUC1 expression inhibited migration and invasion, and induced apoptosis of PANC-1 cells via downregulation of Slug and upregulation of Slug dependent PUMA and E-cadherin expression. MUC1 could serve as a potential therapeutic target in pancreatic cancer.

  16. MUC1 (CD227) interacts with lck tyrosine kinase in Jurkat lymphoma cells and normal T cells.

    Science.gov (United States)

    Mukherjee, P; Tinder, T L; Basu, G D; Gendler, S J

    2005-01-01

    MUC1 (CD227) is a large transmembrane epithelial mucin glycoprotein, which is aberrantly overexpressed in most adenocarcinomas and is a target for immune therapy for epithelial tumors. Recently, MUC1 has been detected in a variety of hematopoietic cell malignancies including T and B cell lymphomas and myelomas; however, its function in these cells is not clearly defined. Using the Jurkat T cell lymphoma cell line and normal human T cells, we demonstrate that MUC1 is not only expressed in these cells but is also phosphorylated upon T cell receptor (TCR) ligation and associates with the Src-related T cell tyrosine kinase, p56lck. Upon TCR-mediated activation of Jurkat cells, MUC1 is found in the low-density membrane fractions, where linker of T cell activation is contained. Abrogation of MUC1 expression in Jurkat cells by MUC1-specific small interfering RNA resulted in defects in TCR-mediated downstream signaling events associated with T cell activation. These include reduction in Ca2+ influx and extracellular signal-regulated kinase 1/2 phosphorylation, leading to a decrease in CD69 expression, proliferation, and interleukin-2 production. These results suggest a regulatory role of MUC1 in modulating proximal signal transduction events through its interaction with proteins of the activation complex.

  17. Characterization of a novel weak interaction between MUC1 and Src-SH3 using nuclear magnetic resonance spectroscopy

    Energy Technology Data Exchange (ETDEWEB)

    Gunasekara, Nirosha [Department of Laboratory Medicine and Pathology, University of Alberta, 5B4.21 WCM Health Science Centre, 8440-112th Street, Edmonton, Alberta, Canada T6G 2R7 (Canada); Sykes, Brian, E-mail: brian.sykes@ualberta.ca [Department of Biochemistry, 4-19B Medical Sciences Bldg., University of Alberta Edmonton, Alberta, Canada T6G 2H7 (Canada); Hugh, Judith, E-mail: judithh@ualberta.ca [Department of Laboratory Medicine and Pathology, University of Alberta, 5B4.21 WCM Health Science Centre, 8440-112th Street, Edmonton, Alberta, Canada T6G 2R7 (Canada)

    2012-05-18

    Highlights: Black-Right-Pointing-Pointer MUC1 binds the Src-SH3 domain potentially triggering Src dependent cell migration. Black-Right-Pointing-Pointer NMR Spectroscopy was used to monitor MUC1-CD and Src SH3 domain titrations. Black-Right-Pointing-Pointer MUC1-CD peptides bind with a low affinity (K{sub d} of 2-3 mM) to a non-canonical site. Black-Right-Pointing-Pointer Weak interactions may mediate dynamic processes like migration. Black-Right-Pointing-Pointer The MUC1-CD and Src-SH3 interaction may be a prime target to inhibit cell migration. -- Abstract: Breast cancer causes death through cancer cell migration and subsequent metastasis to distant organs. In vitro, the MUC1 mucin can mediate breast cancer cell migration by binding to intercellular adhesion molecule-1 (ICAM-1). This migration is dependent on MUC1 cytoplasmic domain (MUC1-CD) activation of the non-receptor tyrosine kinase, Src, possibly through competitive displacement of an inhibitory Src intramolecular SH3 binding. Therefore, we characterized the binding site and affinity of the MUC1-CD for Src-SH3 using multidimensional nuclear magnetic resonance (NMR) spectroscopy to monitor the titration of the {sup 15}N labeled Src-SH3 domain with synthetic native and mutant peptides of MUC1-CD. The results revealed that the dissociation constant (K{sub d}) for the interaction of the native MUC1-CD peptides and Src-SH3 domain was weak with a K{sub d} of 2-3 mM. Notably, the SH3 residues most perturbed upon peptide binding were located outside the usual hydrophobic binding cleft in a previously described alternate binding site on the Src-SH3, suggesting that MUC1-CD binds to a non-canonical site. The binding characteristics outlined here suggest that the interaction between Src-SH3 and MUC1-CD represents a novel weak electrostatic interaction of the type which is increasingly recognized as important in transient and dynamic protein complexes required for cell migration and signal transduction. As such, this

  18. Prognostic Significance of Mucin Antigen MUC1 in Various Human Epithelial Cancers: A Meta-Analysis.

    Science.gov (United States)

    Xu, Feng; Liu, Fuquan; Zhao, Hongwei; An, Guangyu; Feng, Guosheng

    2015-12-01

    Accumulating evidence indicates that mucin antigen MUC1 plays a fundamental role in the initiation and progression of several types of epithelial carcinomas. However, whether the expression of MUC1 on tumor cells is associated with patients' survival remains controversial. Medline/PubMed, EMBASE, the Cochrane Library, Chinese National Knowledge Infrastructure (CNKI) databases, and Grey literature were searched up to 15 August 2015 for eligible studies of the association between the MUC1 expression and overall survival (OS) in various epithelial cancers. The hazard ratio (HR) and its 95% confidence interval (CI) were calculated from the included studies. Moreover, the odds ratio (OR) was also extracted to evaluate the association between the clinicopathological parameters of participants and MUC1 expression. A total of 3425 patients covering 23 studies were included in the analysis. The pooled results showed that positive MUC1 staining was a negative predictor of OS (HRFEM = 1.98,95% CIFEM: 1.76-2.22, PFEM = 0.479; HRREM = 2.16,95% CIREM: 1.58-2.94, PREM = 0.355) in various epithelial carcinomas. Subgroup analysis revealed that the increased MUC1 expression was significantly associated with poor OS in patients with gastric cancer (HRFEM = 2.12, 95%CIFEM: 1.75-2.57, PFEM = 0.359; HRREM = 1.89, 95% CIREM: 1.05-3.41, PREM = 0.238), colorectal cancer (HRFEM = 1.73, 95%CIFEM: 1.41-2.13, PFEM = 0.048; HRREM = 2.00,95% CIREM: 1.46-2.73, PREM = 0.019), cholangiocarcinoma (HRFEM = 2.52, 95% CIFEM: 1.42-4.49, PFEM = 0.252; HRREM = 2.34, 95% CIREM: 1.30-4.22, PREM = 0.244), and nonsmall cell lung cancer (NSCLC) (HRFEM = 2.14, 95% CIFEM: 1.46-3.14, PFEM = 0.591; HRREM = 2.81, 95% CIREM: 1.40-5.64, PREM = 0.280). In addition, MUC1 overexpression was more likely to be found in colorectal cancer patients with an advanced tumor node metastasis stage (ORREM = 1.55, 95% CIREM: 1.06-2.27; PREM = 0

  19. Prognostic Significance of Mucin Antigen MUC1 in Various Human Epithelial Cancers

    Science.gov (United States)

    Xu, Feng; Liu, Fuquan; Zhao, Hongwei; An, Guangyu; Feng, Guosheng

    2015-01-01

    Abstract Accumulating evidence indicates that mucin antigen MUC1 plays a fundamental role in the initiation and progression of several types of epithelial carcinomas. However, whether the expression of MUC1 on tumor cells is associated with patients’ survival remains controversial. Medline/PubMed, EMBASE, the Cochrane Library, Chinese National Knowledge Infrastructure (CNKI) databases, and Grey literature were searched up to 15 August 2015 for eligible studies of the association between the MUC1 expression and overall survival (OS) in various epithelial cancers. The hazard ratio (HR) and its 95% confidence interval (CI) were calculated from the included studies. Moreover, the odds ratio (OR) was also extracted to evaluate the association between the clinicopathological parameters of participants and MUC1 expression. A total of 3425 patients covering 23 studies were included in the analysis. The pooled results showed that positive MUC1 staining was a negative predictor of OS (HRFEM = 1.98,95% CIFEM: 1.76–2.22, PFEM = 0.479; HRREM = 2.16,95% CIREM: 1.58–2.94, PREM = 0.355) in various epithelial carcinomas. Subgroup analysis revealed that the increased MUC1 expression was significantly associated with poor OS in patients with gastric cancer (HRFEM = 2.12, 95%CIFEM: 1.75–2.57, PFEM = 0.359; HRREM = 1.89, 95% CIREM: 1.05–3.41, PREM = 0.238), colorectal cancer (HRFEM = 1.73, 95%CIFEM: 1.41–2.13, PFEM = 0.048; HRREM = 2.00,95% CIREM: 1.46–2.73, PREM = 0.019), cholangiocarcinoma (HRFEM = 2.52, 95% CIFEM: 1.42–4.49, PFEM = 0.252; HRREM = 2.34, 95% CIREM: 1.30–4.22, PREM = 0.244), and nonsmall cell lung cancer (NSCLC) (HRFEM = 2.14, 95% CIFEM: 1.46–3.14, PFEM = 0.591; HRREM = 2.81, 95% CIREM: 1.40–5.64, PREM = 0.280). In addition, MUC1 overexpression was more likely to be found in colorectal cancer patients with an advanced tumor node metastasis stage (ORREM = 1.55, 95

  20. Preparation and preliminary studies of [64Cu]-antiMUC-1 for breast cancer targeting

    Directory of Open Access Journals (Sweden)

    Behrouz Alirezapour

    2016-06-01

    Full Text Available PR81 is a monoclonal antibody that binds with high affinity to MUC1 that over expressed on breast tumors. PR81 is considered a suitable targeting molecule that was radiolabeled using Cu-64 for positron imaging studies. The monoclonal antibody was conjugated with DOTA moiety and after purification was evaluated for radiochemical purity, immunoreactivity, cell toxicity and structure integrity as well as biodistribution study in normal rats. The radiolabeled antibody prepared with acceptable radiochemical purity (> 93.2 ± 0.6 %, ITLC; specific activity; 4.6 µCi/µg, protein structure integration, significant cytotoxicity and significant immunoreactivity retention was assessed by radioimmunoassay (RIA. Animal biodistribution of the 64Cu-DOTA-PR81 was consistent with other radiolabeled antibodies. The results showed that 64Cu-DOTA-PR81 may be considered for tumor imaging for ultimate diagnosis and follow-up of MUC1 expression in oncology.

  1. Development of [⁶⁴Cu]-DOTA-PR81 radioimmunoconjugate for MUC-1 positive PET imaging.

    Science.gov (United States)

    Alirezapour, Behrouz; Rasaee, Mohammad Javad; Jalilian, Amir Reza; Rajabifar, Saeed; Mohammadnejad, Javad; Paknejad, Malihe; Maadi, Ehsan; Moradkhani, Sedigheh

    2016-01-01

    Breast cancer radioimmunoscintigraphy targeting MUC1 expression is a growing field of work in nuclear medicine research. PR81 is a monoclonal antibody that binds with high affinity to MUC1, which is over expressed on breast tumors. In this study, we report production, quality control and preclinical qualifications of a copper-64 labeled PR81 for PET imaging of breast cancer. PR81 was conjugated with DOTA-NHS-ester and purified by molecular filtration followed by chelate:mAb ratio determination by spectrophotometric method. DOTA-PR81 was labeled with (64)Cu followed by radiochemical purity, in vitro stability, in vitro internalization and immunoreactivity determination. The tissue biodistribution of the (64)Cu-DOTA-PR81 and (64)Cu-DOTA-hIgG was evaluated in BALB/c mice with breast carcinoma tumors using tissue counting and imaging. The radiochemical purity of radioimmunoconjugate was >95±1.9% (ITLC) (specific activity; 4.6 μCi/μg). The average number of chelators per antibody was 3.4±0.3:1. The (64)Cu-DOTA-PR81 showed immunoreactivity towards MUC1 antigen and MCF7 cell line with significant in vitro stability (>89% in PBS and 78±0.5% in human serum) over 48 h. Maximum internalized activity of radiolabeled PR81 in 4-8 h was 81.5%. The biodistribution and scintigraphy studies showed the accumulation of the complex at the site of tumors with high sensitivity and specificity compared to control probes. The results showed that (64)Cu-DOTA-PR81 may be considered as a potential PET tracer for diagnosis and follow-up of MUC1 expression in oncology. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. Impact of MUC1 mucin downregulation in the phenotypic characteristics of MKN45 gastric carcinoma cell line.

    Directory of Open Access Journals (Sweden)

    Natália R Costa

    Full Text Available BACKGROUND: Gastric carcinoma is the second leading cause of cancer-associated death worldwide. The high mortality associated with this disease is in part due to limited knowledge about gastric carcinogenesis and a lack of available therapeutic and prevention strategies. MUC1 is a high molecular weight transmembrane mucin protein expressed at the apical surface of most glandular epithelial cells and a major component of the mucus layer above gastric mucosa. Overexpression of MUC1 is found in approximately 95% of human adenocarcinomas, where it is associated with oncogenic activity. The role of MUC1 in gastric cancer progression remains to be clarified. METHODOLOGY: We downregulated MUC1 expression in a gastric carcinoma cell line by RNA interference and studied the effects on cellular proliferation (MTT assay, apoptosis (TUNEL assay, migration (migration assay, invasion (invasion assay and aggregation (aggregation assay. Global gene expression was evaluated by microarray analysis to identify alterations that are regulated by MUC1 expression. In vivo assays were also performed in mice, in order to study the tumorigenicity of cells with and without MUC1 downregulation in MKN45 gastric carcinoma cell line. RESULTS: Downregulation of MUC1 expression increased proliferation and apoptosis as compared to controls, whereas cell-cell aggregation was decreased. No significant differences were found in terms of migration and invasion between the downregulated clones and the controls. Expression of TCN1, KLK6, ADAM29, LGAL4, TSPAN8 and SHPS-1 was found to be significantly different between MUC1 downregulated clones and the control cells. In vivo assays have shown that mice injected with MUC1 downregulated cells develop smaller tumours when compared to mice injected with the control cells. CONCLUSIONS: These results indicate that MUC1 downregulation alters the phenotype and tumorigenicity of MKN45 gastric carcinoma cells and also the expression of several

  3. Induction of protective and therapeutic anti-pancreatic cancer immunity using a reconstructed MUC1 DNA vaccine

    International Nuclear Information System (INIS)

    Rong, Yefei; Jin, Dayong; Wu, Wenchuan; Lou, Wenhui; Wang, Danshong; Kuang, Tiantao; Ni, Xiaoling; Qin, Xinyu

    2009-01-01

    Pancreatic cancer is a common, highly lethal disease with a rising incidence. MUC1 is a tumor-associated antigen that is over-expressed in pancreatic adenocarcinoma. Active immunotherapy that targets MUC1 could have great treatment value. Here we investigated the preventive and therapeutic effect of a MUC1 DNA vaccine on the pancreatic cancer. MUC1-various tandem repeat units(VNTR) DNA vaccine was produced by cloning one repeat of VNTR and inserting the cloned gene into the pcDNA3.1. In the preventive group, female C57BL/6 mice were immunized with the vaccine, pcDNA3.1 or PBS; and challenged with panc02-MUC1 or panc02 cell. In the therapeutic group the mice were challenged with panc02-MUC1 or panc02 cell, and then immunized with the vaccine, pcDNA3.1 or PBS. The tumor size and the survival time of the animals were compared between these groups. The DNA vaccine pcDNA3.1-VNTR could raise cytotoxic T lymphocyte (CTL) activity specific for MUC1. In the preventive experiment, the mice survival time was significantly longer in the vaccine group than in the control groups (P < 0.05). In the therapeutic experiment, the DNA vaccine prolonged the survival time of the panc02-MUC1-bearing mice (P < 0.05). In both the preventive and therapeutic experiments, the tumor size was significantly less in the vaccine group than in the control groups (P < 0.05). This pcDNA3.1-VNTR vaccine, however, could not prevent the mice attacked by panc02 cells and had no therapeutic effect on the mice attacked by panc02 cells. The MUC1 DNA vaccine pcDNA3.1-VNTR could induce a significant MUC1-specific CTL response; and had both prophylactic and therapeutic effect on panc02-MUC1 tumors. This vaccine might be used as a new adjuvant strategy against pancreatic cancer

  4. MUC1 Expression by Immunohistochemistry Is Associated with Adverse Pathologic Features in Prostate Cancer: A Multi-Institutional Study.

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    Okyaz Eminaga

    Full Text Available The uncertainties inherent in clinical measures of prostate cancer (CaP aggressiveness endorse the investigation of clinically validated tissue biomarkers. MUC1 expression has been previously reported to independently predict aggressive localized prostate cancer. We used a large cohort to validate whether MUC1 protein levels measured by immunohistochemistry (IHC predict aggressive cancer, recurrence and survival outcomes after radical prostatectomy independent of clinical and pathological parameters.MUC1 IHC was performed on a multi-institutional tissue microarray (TMA resource including 1,326 men with a median follow-up of 5 years. Associations with clinical and pathological parameters were tested by the Chi-square test and the Wilcoxon rank sum test. Relationships with outcome were assessed with univariable and multivariable Cox proportional hazard models and the Log-rank test.The presence of MUC1 expression was significantly associated with extracapsular extension and higher Gleason score, but not with seminal vesicle invasion, age, positive surgical margins or pre-operative serum PSA levels. In univariable analyses, positive MUC1 staining was significantly associated with a worse recurrence free survival (RFS (HR: 1.24, CI 1.03-1.49, P = 0.02, although not with disease specific survival (DSS, P>0.5. On multivariable analyses, the presence of positive surgical margins, extracapsular extension, seminal vesicle invasion, as well as higher pre-operative PSA and increasing Gleason score were independently associated with RFS, while MUC1 expression was not. Positive MUC1 expression was not independently associated with disease specific survival (DSS, but was weakly associated with overall survival (OS.In our large, rigorously designed validation cohort, MUC1 protein expression was associated with adverse pathological features, although it was not an independent predictor of outcome after radical prostatectomy.

  5. Rise and fall of an anti-MUC1 specific antibody.

    Directory of Open Access Journals (Sweden)

    Holger Thie

    2011-01-01

    Full Text Available So far, human antibodies with good affinity and specificity for MUC1, a transmembrane protein overexpressed on breast cancers and ovarian carcinomas, and thus a promising target for therapy, were very difficult to generate.A human scFv antibody was isolated from an immune library derived from breast cancer patients immunised with MUC1. The anti-MUC1 scFv reacted with tumour cells in more than 80% of 228 tissue sections of mamma carcinoma samples, while showing very low reactivity with a large panel of non-tumour tissues. By mutagenesis and phage display, affinity of scFvs was increased up to 500fold to 5,7×10(-10 M. Half-life in serum was improved from below 1 day to more than 4 weeks and was correlated with the dimerisation tendency of the individual scFvs. The scFv bound to T47D and MCF-7 mammalian cancer cell lines were recloned into the scFv-Fc and IgG format resulting in decrease of affinity of one binder. The IgG variants with the highest affinity were tested in mouse xenograft models using MCF-7 and OVCAR tumour cells. However, the experiments showed no significant decrease in tumour growth or increase in the survival rates. To study the reasons for the failure of the xenograft experiments, ADCC was analysed in vitro using MCF-7 and OVCAR3 target cells, revealing a low ADCC, possibly due to internalisation, as detected for MCF-7 cells.Antibody phage display starting with immune libraries and followed by affinity maturation is a powerful strategy to generate high affinity human antibodies to difficult targets, in this case shown by the creation of a highly specific antibody with subnanomolar affinity to a very small epitope consisting of four amino acids. Despite these "best in class" binding parameters, the therapeutic success of this antibody was prevented by the target biology.

  6. Targeting of the MUC1-C Oncoprotein in Colitis-Associated Colorectal Cancer

    Science.gov (United States)

    2013-09-01

    effect- level isobologram analysis is shown for ED 90 (), ED 75 (+) and ED 50 (×) with the right side panel indicating the CI index for the...was generated by exposing the cells to fixed IC50 ratios of GO-203, GSK1120212 and the GO- 203/GSK1120212 combination. The multiple effect- level ...Kharbanda S, and Kufe D, MUC1 oncoprotein blocks GSK3β -mediated phosphorylation and degradation of β-catenin. Cancer Res, 2005. 65:10413-22. 11. Rajabi

  7. Autosomal Dominant Tubulointerstitial Kidney Disease: Clinical Presentation of Patients With ADTKD-UMOD and ADTKD-MUC1.

    Science.gov (United States)

    Ayasreh, Nadia; Bullich, Gemma; Miquel, Rosa; Furlano, Mónica; Ruiz, Patricia; Lorente, Laura; Valero, Oliver; García-González, Miguel Angel; Arhda, Nisrine; Garin, Intza; Martínez, Víctor; Pérez-Gómez, Vanessa; Fulladosa, Xavier; Arroyo, David; Martínez-Vea, Alberto; Espinosa, Mario; Ballarín, Jose; Ars, Elisabet; Torra, Roser

    2018-05-18

    Autosomal dominant tubulointerstitial kidney disease (ADTKD) is a rare underdiagnosed cause of end-stage renal disease (ESRD). ADTKD is caused by mutations in at least 4 different genes: MUC1, UMOD, HNF1B, and REN. Retrospective cohort study. 56 families (131 affected individuals) with ADTKD referred from different Spanish hospitals. Clinical, laboratory, radiologic, and pathologic data were collected, and genetic testing for UMOD, MUC1, REN, and HNF1B was performed. Hyperuricemia, ultrasound findings, renal histology, genetic mutations. Age at ESRD, rate of decline in estimated glomerular filtration rate. ADTKD was diagnosed in 25 families (45%), 9 carried UMOD pathogenic variants (41 affected members), and 16 carried the MUC1 pathogenic mutation c.(428)dupC (90 affected members). No pathogenic variants were identified in REN or HNF1B. Among the 77 individuals who developed ESRD, median age at onset of ESRD was 51 years for those with ADTKD-MUC1 versus 56 years (P=0.1) for those with ADTKD-UMOD. Individuals with the MUC1 duplication presented higher risk for developing ESRD (HR, 2.24; P=0.03). The slope of decline in estimated glomerular filtration rate showed no significant difference between groups (-3.0mL/min/1.73m 2 per year in the ADTKD-UMOD group versus -3.9mL/min/1.73m 2 per year in the ADTKD-MUC1 group; P=0.2). The prevalence of hyperuricemia was significantly higher in individuals with ADTKD-UMOD (87% vs 54%; P=0.006). Although gout occurred more frequently in this group, the difference was not statistically significant (24% vs 7%; P=0.07). Relatively small Spanish cohort. MUC1 analysis limited to cytosine duplication. The main genetic cause of ADTKD in our Spanish cohort is the MUC1 pathogenic mutation c.(428)dupC. Renal survival may be worse in individuals with the MUC1 mutation than in those with UMOD mutations. Clinical presentation does not permit distinguishing between these variants. However, hyperuricemia and gout are more frequent in individuals

  8. The Cytoplasmic Domain of MUC1 Induces Hyperplasia in the Mammary Gland and Correlates with Nuclear Accumulation of β-Catenin

    Science.gov (United States)

    Li, Yuan; Yi, Haiying; Yao, Yixin; Liao, Xiaodong; Xie, Yiqun; Yang, Jie; Yan, Zheng; Wang, Long; Lu, Shunyuan; Kuang, Ying; Gu, Mingmin; Fei, Jian; Wang, Zhugang; Huang, Lei

    2011-01-01

    MUC1 is an oncoprotein that is overexpressed in up to 90% of breast carcinomas. A previous in vitro study by our group demonstrated that the cytoplasmic domain of MUC1 (MUC1-CD), the minimal functional unit of MUC1, contributes to the malignant phenotype in cells by binding directly to β-catenin and protecting β-catenin from GSK3β-induced degradation. To understand the in vivo role of MUC1-CD in breast development, we generated a MUC1-CD transgenic mouse model under the control of the MMTV promoter in a C57BL/6J background, which is more resistant to breast tumor. We show that the expression of MUC1-CD in luminal epithelial cells of the mammary gland induced a hyperplasia phenotype characterized by the development of hyper-branching and extensive lobuloalveoli in transgenic mice. In addition to this hyperplasia, there was a marked increase in cellular proliferation in the mouse mammary gland. We further show that MUC1-CD induces nuclear localization of β-catenin, which is associated with a significant increase of β-catenin activity, as shown by the elevated expression of cyclin D1 and c-Myc in MMTV-MUC1-CD mice. Consistent with this finding, we observed that overexpression of MUC1-C is associated with β-catenin nuclear localization in tumor tissues and increased expression of Cyclin D1 and c-Myc in breast carcinoma specimens. Collectively, our data indicate a critical role for MUC1-CD in the development of mammary gland preneoplasia and tumorigenesis, suggesting MUC1-CD as a potential target for the diagnosis and chemoprevention of human breast cancer. PMID:21533058

  9. The cytoplasmic domain of MUC1 induces hyperplasia in the mammary gland and correlates with nuclear accumulation of β-catenin.

    Directory of Open Access Journals (Sweden)

    Yuan Li

    Full Text Available MUC1 is an oncoprotein that is overexpressed in up to 90% of breast carcinomas. A previous in vitro study by our group demonstrated that the cytoplasmic domain of MUC1 (MUC1-CD, the minimal functional unit of MUC1, contributes to the malignant phenotype in cells by binding directly to β-catenin and protecting β-catenin from GSK3β-induced degradation. To understand the in vivo role of MUC1-CD in breast development, we generated a MUC1-CD transgenic mouse model under the control of the MMTV promoter in a C57BL/6J background, which is more resistant to breast tumor. We show that the expression of MUC1-CD in luminal epithelial cells of the mammary gland induced a hyperplasia phenotype characterized by the development of hyper-branching and extensive lobuloalveoli in transgenic mice. In addition to this hyperplasia, there was a marked increase in cellular proliferation in the mouse mammary gland. We further show that MUC1-CD induces nuclear localization of β-catenin, which is associated with a significant increase of β-catenin activity, as shown by the elevated expression of cyclin D1 and c-Myc in MMTV-MUC1-CD mice. Consistent with this finding, we observed that overexpression of MUC1-C is associated with β-catenin nuclear localization in tumor tissues and increased expression of Cyclin D1 and c-Myc in breast carcinoma specimens. Collectively, our data indicate a critical role for MUC1-CD in the development of mammary gland preneoplasia and tumorigenesis, suggesting MUC1-CD as a potential target for the diagnosis and chemoprevention of human breast cancer.

  10. Therapeutic efficacy of MUC1-specific cytotoxic T lymphocytes and CD137 co-stimulation in a spontaneous breast cancer model.

    Science.gov (United States)

    Mukherjee, Pinku; Tinder, Teresa L; Basu, Gargi D; Pathangey, Latha B; Chen, Lieping; Gendler, Sandra J

    2004-01-01

    To study immunology in breast tumors, we have utilized a mammary gland adenocarcinoma model in which mice develop spontaneous tumors of the mammary gland which are initiated at puberty and express a human tumor antigen, MUC1. MUC1 (CD227) is over-expressed in 90% of human breast cancers and its glycosylation status and pattern of expression in cancer cells is altered. Humoral and cellular responses to MUC1 have been reported in breast cancer patients and therefore, MUC1 is being evaluated as a target for immune intervention. This mouse model of spontaneous breast cancer allows the evaluation of anti-MUC1 immune responses at all stages of the disease. In this report, we review the model as it pertains to a) the development of the tumor, b) MUC1 expression, and the native immune responses against MUC1 as tumors progress, and c) the immune suppressive microenvironment within the developing tumor. Finally, we report our latest findings describing the therapeutic efficacy of adoptively transferred MUC1-specific cytotoxic T lymphocytes (MUC1-CTL) in these mice and discuss ways to increase their effectiveness by agonistic monoclonal antibody against CD137 T cell costimulatory molecule.

  11. Design of α-S-Neoglycopeptides Derived from MUC1 with a Flexible and Solvent-Exposed Sugar Moiety

    DEFF Research Database (Denmark)

    Rojas-Ocáriz, Víctor; Compañón, Ismael; Aydillo Miguel, Carlos

    2016-01-01

    in solution have been evaluated by combining NMR experiments and molecular dynamics simulations. The linker plays a key role in the modulation of the conformation of these compounds at different levels, blocking a direct contact between the sugar moiety and the backbone, promoting a helix-like conformation...... for the glycosylated residue and favoring the proper presentation of the sugar unit for molecular recognition events. The feasibility of these novel compounds as mimics of MUC1 antigens has been validated by the X-ray diffraction structure of one of these unnatural derivatives complexed to an anti-MUC1 monoclonal...

  12. Rise and Fall of an Anti-MUC1 Specific Antibody

    Science.gov (United States)

    Li, Jiandong; von Wasielewski, Reinhard; Bastert, Gunther; Schirrmann, Thomas; Esteves, Isabel Tourais; Behrens, Christian K.; Fournes, Bénédict; Fournier, Nathalie; de Romeuf, Christophe; Hust, Michael; Dübel, Stefan

    2011-01-01

    Background So far, human antibodies with good affinity and specificity for MUC1, a transmembrane protein overexpressed on breast cancers and ovarian carcinomas, and thus a promising target for therapy, were very difficult to generate. Results A human scFv antibody was isolated from an immune library derived from breast cancer patients immunised with MUC1. The anti-MUC1 scFv reacted with tumour cells in more than 80% of 228 tissue sections of mamma carcinoma samples, while showing very low reactivity with a large panel of non-tumour tissues. By mutagenesis and phage display, affinity of scFvs was increased up to 500fold to 5,7×10−10 M. Half-life in serum was improved from below 1 day to more than 4 weeks and was correlated with the dimerisation tendency of the individual scFvs. The scFv bound to T47D and MCF-7 mammalian cancer cell lines were recloned into the scFv-Fc and IgG format resulting in decrease of affinity of one binder. The IgG variants with the highest affinity were tested in mouse xenograft models using MCF-7 and OVCAR tumour cells. However, the experiments showed no significant decrease in tumour growth or increase in the survival rates. To study the reasons for the failure of the xenograft experiments, ADCC was analysed in vitro using MCF-7 and OVCAR3 target cells, revealing a low ADCC, possibly due to internalisation, as detected for MCF-7 cells. Conclusions Antibody phage display starting with immune libraries and followed by affinity maturation is a powerful strategy to generate high affinity human antibodies to difficult targets, in this case shown by the creation of a highly specific antibody with subnanomolar affinity to a very small epitope consisting of four amino acids. Despite these “best in class” binding parameters, the therapeutic success of this antibody was prevented by the target biology. PMID:21264246

  13. MUC1 positive cutaneous metastasis with transepidermal elimination from a breast carcinoma

    Directory of Open Access Journals (Sweden)

    Luna A

    2013-11-01

    Full Text Available Amalia Luna, Maria Emilia Merino, Cecilio G Alberdi, Martin C Abba, Amada Segal-Eiras, Maria Virginia Croce Center of Basic and Applied Immunological Research, Faculty of Medical Sciences, National University of La Plata, Argentina Abstract: Breast cancer is the most common cause of cutaneous metastases from internal malignancies. Generally, the neoplastic cells are located in the dermis or hypodermis, while a finding of transepidermal elimination on cutaneous metastases is exceptional. In this report we present a patient with perforating cutaneous metastases from breast cancer with mucin 1 expression. Cutaneous, bone, lung, and hepatic lesions were detected two years after the diagnosis of the primary tumor. Keywords: breast cancer, cutaneous metastasis, transepidermal elimination, MUC1

  14. Mannan-MUC1-pulsed dendritic cell immunotherapy: a phase I trial in patients with adenocarcinoma.

    Science.gov (United States)

    Loveland, Bruce E; Zhao, Anne; White, Shane; Gan, Hui; Hamilton, Kate; Xing, Pei-Xiang; Pietersz, Geoffrey A; Apostolopoulos, Vasso; Vaughan, Hilary; Karanikas, Vaios; Kyriakou, Peter; McKenzie, Ian F C; Mitchell, Paul L R

    2006-02-01

    Tumor antigen-loaded dendritic cells show promise for cancer immunotherapy. This phase I study evaluated immunization with autologous dendritic cells pulsed with mannan-MUC1 fusion protein (MFP) to treat patients with advanced malignancy. Eligible patients had adenocarcinoma expressing MUC1, were of performance status 0 to 1, with no autoimmune disease. Patients underwent leukapheresis to generate dendritic cells by culture ex vivo with granulocyte macrophage colony-stimulating factor and interleukin 4 for 5 days. Dendritic cells were then pulsed overnight with MFP and harvested for reinjection. Patients underwent three cycles of leukapheresis and reinjection at monthly intervals. Patients with clinical benefit were able to continue with dendritic cell-MFP immunotherapy. Ten patients with a range of tumor types were enrolled, with median age of 60 years (range, 33-70 years); eight patients were of performance status 0 and two of performance status 1. Dendritic cell-MFP therapy led to strong T-cell IFNgamma Elispot responses to the vaccine and delayed-type hypersensitivity responses at injection sites in nine patients who completed treatments. Immune responses were sustained at 1 year in monitored patients. Antibody responses were seen in three patients only and were of low titer. Side effects were grade 1 only. Two patients with clearly progressive disease (ovarian and renal carcinoma) at entry were stable after initial therapy and went on to further leukapheresis and dendritic cell-MFP immunotherapy. These two patients have now each completed over 3 years of treatment. Immunization produced T-cell responses in all patients with evidence of tumor stabilization in 2 of the 10 advanced cancer patients treated. These data support further clinical evaluation of this dendritic cell-MFP immunotherapy.

  15. Aberrantly glycosylated MUC1 is expressed on the surface of breast cancer cells and a target for antibody-dependent cell-mediated cytotoxicity

    DEFF Research Database (Denmark)

    Lavrsen, Kirstine; Madsen, Caroline B; Rasch, Morten G

    2013-01-01

    to Tn-MUC1 was investigated using BiaCore. The availability of Tn-MUC1 on the surface of breast cancer cells was evaluated by immunohistochemistry, confocal microscopy, and flow cytometry, followed by in vitro assessment of antibody-dependent cellular cytotoxicity by mAb 5E5. Biacore analysis...

  16. Microvesicle Cargo of Tumor-Associated MUC1 to Dendritic Cells Allows Cross-presentation and Specific Carbohydrate Processing

    DEFF Research Database (Denmark)

    Rughetti, Aurelia; Rahimi, Hassan; Belleudi, Francesca

    2014-01-01

    Tumor-associated glycoproteins are a group of antigens with high immunogenic interest: The glycoforms generated by the aberrant glycosylation are tumor-specific and the novel glycoepitopes exposed can be targets of tumor-specific immune responses. The MUC1 antigen is one of the most relevant tumo...

  17. MUC1 in human milk blocks transmission of human immunodeficiency virus from dendritic cells to T cells

    NARCIS (Netherlands)

    Saeland, E.; Jong, de M.A.W.P.; Nabatov, A.; Kalay, H.; Kooijk, van Y.; Geijtenbeek, T.B.H.

    2009-01-01

    Mother-to-child transmission of human immunodeficiency virus-1 (HIV-1) occurs frequently via breast-feeding. HIV-1 targets DC-SIGN+ dendritic cells (DCs) in mucosal areas that allow efficient transmission of the virus to T cells. Here, we demonstrate that the epithelial mucin MUC1, abundant in milk,

  18. Detection of glyco-mucin profiles improves specificity of MUC16 and MUC1 biomarkers in ovarian serous tumours

    DEFF Research Database (Denmark)

    Ricardo, Sara; da Silva, Lara Patricia Marcos; Pereira, Daniela

    2015-01-01

    The CA125 assay detects circulating MUC16 and is one of the most widely used cancer biomarkers for the follow-up of ovarian cancer. We previously demonstrated that detection of aberrant cancer-associated glycoforms of MUC16 as well as MUC1 in circulation could improve the yield of these serum ass...

  19. Intact glycopeptide characterization using mass spectrometry

    OpenAIRE

    Cao, Li; Qu, Yi; Zhang, Zhaorui; Wang, Zhe; Prykova, Iya; Wu, Si

    2016-01-01

    Glycosylation is one of the most prominent and extensively studied protein post-translational modifications. However, traditional proteomic studies at the peptide level (bottom-up) rarely characterize intact glycopeptides (glycosylated peptides without removing glycans), so no glycoprotein heterogeneity information is retained. Intact glycopeptide characterization, on the other hand, provides opportunities to simultaneously elucidate the glycan structure and the glycosylation site needed to r...

  20. In vivo and in vitro studies of MUC1 regulation in sheep endometrium.

    Science.gov (United States)

    Raheem, Kabir A; Marei, Waleed F A; Campbell, Bruce K; Fouladi-Nashta, Ali A

    2016-06-01

    In this study, we investigated the expression of mucin 1 (MUC1) mRNA and protein in sheep endometrium at different time points during follicular and luteal phases of estrous cycle, and also determined the effect of steroid hormone treatments and interferon tau (IFNτ) on MUC1 mRNA expression in endometrial cell culture in vitro. In experiment one, 15 Welsh mountain ewes were synchronized to a common estrus and killed at precise stages of estrous cycle corresponding to (1) pre-LH peak, (2) LH peak, (3) post-LH peak, (4) early luteal, and (5) mid-luteal. Reproductive tracts were harvested and mRNA was extracted from the endometrial tissues. Parts of the uterine horns were fixed for immunohistochemistry. In experiment two, mixed populations of ovine endometrial cells (from slaughterhouse material collected at the postovulatory stage of the estrous cycle) were cultured to 70% confluence before treatment with (1) progesterone (P4, 10 ng/mL, for 48 hours), (2) estradiol (E2, 100 pg/mL, for 48 hours), or with (3) E2 priming for 12 hours (100 pg/mL) followed by P4 (10 ng/mL) for 36 hours. These were compared with: (4) IFNτ (10 ng/mL, for 48 hours), and (5) basic medium (Dulbecco Modified Eagle Medium /F12) as control. The results showed that MUC1 mRNA and protein expression in sheep endometrium were highest during the midluteal stage and very low during the post-LH period compared with the other stages (P < 0.05). MUC1 immunostaining in the luminal epithelium was apically restricted and was not significantly different across all stages of estrous cycle except at the post-LH peak where it was significantly low. In cell culture, MUC1 mRNA expression was significantly upregulated by both steroids either singly or in combination (P < 0.05), and downregulated in the presence of IFNτ. In conclusion, endometrial MUC1 expression is cyclically regulated by both E2 and P4in vivo and in vitro, and directly downregulated by IFNτ treatment in vitro. Copyright © 2016

  1. Human milk blocks DC-SIGN - pathogen interaction via MUC1

    Directory of Open Access Journals (Sweden)

    Nathalie eKoning

    2015-03-01

    Full Text Available Beneficial effects of breastfeeding are well-recognized and include both immediate neonatal protection against pathogens, as well as long term protection against allergies and autoimmune diseases. Although several proteins have been identified to have anti-viral or anti-bacterial effects like secretory IgA or lactoferrin, the mechanisms of immune modulation are not fully understood. Recent studies identified important beneficial effects of glycans in human milk, such as those expressed in oligosaccharides or on glycoproteins. Glycans are recognized by the carbohydrate receptors C-type lectins on DC and specific tissue macrophages, which exert important functions in immune modulation and immune homeostasis. A well-characterized C-type lectin is DC-SIGN, which binds terminal fucose. The present study shows that in human milk, MUC1 is the major milk glycoprotein that binds to the lectin domain of DC-SIGN and prevents pathogen interaction through the presence of Lewis x-type oligosaccharides. Surprisingly, this was specific for human milk, as formula, bovine or camel milk did not show any presence of proteins that interacted with DC-SIGN. The expression of DC-SIGN is found in young infants along the entire gastro-intestinal tract. Our data thus suggest the importance of human milk glycoproteins for blocking pathogen interaction to DC in young children. Moreover, a potential benefit of human milk later in life in shaping the infants immune system through DC-SIGN cannot be ruled out.

  2. KL-6, a human MUC1 mucin, promotes proliferation and survival of lung fibroblasts

    International Nuclear Information System (INIS)

    Ohshimo, Shinichiro; Yokoyama, Akihito; Hattori, Noboru; Ishikawa, Nobuhisa; Hirasawa, Yutaka; Kohno, Nobuoki

    2005-01-01

    The serum level of KL-6, a MUC1 mucin, is a clinically useful marker for various interstitial lung diseases. Previous studies demonstrated that KL-6 promotes chemotaxis of human fibroblasts. However, the pathophysiological role of KL-6 remains poorly understood. Here, we further investigate the functional aspects of KL-6 in proliferation and apoptosis of lung fibroblasts. KL-6 accelerated the proliferation and inhibited the apoptosis of all human lung fibroblasts examined. An anti-KL-6 monoclonal antibody counteracted both of these effects induced by KL-6 on human lung fibroblasts. The pro-fibroproliferative and anti-apoptotic effects of KL-6 are greater than and additive to those of the maximum effective concentrations of platelet-derived growth factor, basic fibroblast growth factor, and transforming growth factor-β. These findings indicate that increased levels of KL-6 in the epithelial lining fluid may stimulate fibrotic processes in interstitial lung diseases and raise the possibility of applying an anti-KL-6 antibody to treat interstitial lung diseases

  3. The membrane-associated MUC1 improves adhesion of salivary MUC5B on buccal cells. Application to development of an in vitro cellular model of oral epithelium.

    Science.gov (United States)

    Ployon, Sarah; Belloir, Christine; Bonnotte, Aline; Lherminier, Jeannine; Canon, Francis; Morzel, Martine

    2016-01-01

    The mucosal pellicle is a thin layer of salivary proteins, mostly MUC5B mucins, anchored to epithelial oral cells. This pellicle is involved in protection of oral mucosae against abrasion, pathogenic microorganisms or chemical xenobiotics. The present study aimed at studying the involvement of MUC1 in mucosal pellicle formation and more specifically in salivary MUC5B binding using a cell-based model of oral epithelium. MUC1 mRNAs were not detected in TR146 cells, and therefore a stable cell line named TR146/MUC1 expressing this protein was developed by transfection. TR146 and TR146/MUC1 were incubated with human saliva in order to evaluate retention of MUC5B by epithelial cells. The cell surface of both TR146 and TR146/MUC1 was typical of a squamous non-keratinized epithelium, with the presence of numerous microplicae. After incubation for 2h with saliva diluted in culture medium (1:1) and two washes with PBS, saliva deposits on cells appeared as a loose filamentous thin network. MUC5B fluorescent immunostaining evidenced a heterogeneous lining of confluent cell cultures by this salivary mucin but with higher fluorescence on TR146/MUC1 cells. Semi-quantification of MUC5B bound to cells confirmed a better retention by TR146/MUC1, evaluated by Dot Blot (+34.1%, p<0.05) or by immunocytochemistry (+44%, p<0.001). The membrane-bound mucin MUC1 is a factor enhancing the formation of the mucosal pellicle by increasing the binding of salivary MUC5B to oral epithelial cells. An in vitro model suitable to study specifically the function and properties of the mucosal pellicle is proposed. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. Design of glycopeptides used to investigate class II MHC binding and T-cell responses associated with autoimmune arthritis.

    Directory of Open Access Journals (Sweden)

    Ida E Andersson

    Full Text Available The glycopeptide fragment CII259-273 from type II collagen (CII binds to the murine A(q and human DR4 class II Major Histocompatibility Complex (MHC II proteins, which are associated with development of murine collagen-induced arthritis (CIA and rheumatoid arthritis (RA, respectively. It has been shown that CII259-273 can be used in therapeutic vaccination of CIA. This glycopeptide also elicits responses from T-cells obtained from RA patients, which indicates that it has an important role in RA as well. We now present a methodology for studies of (glycopeptide-receptor interactions based on a combination of structure-based virtual screening, ligand-based statistical molecular design and biological evaluations. This methodology included the design of a CII259-273 glycopeptide library in which two anchor positions crucial for binding in pockets of A(q and DR4 were varied. Synthesis and biological evaluation of the designed glycopeptides provided novel structure-activity relationship (SAR understanding of binding to A(q and DR4. Glycopeptides that retained high affinities for these MHC II proteins and induced strong responses in panels of T-cell hybridomas were also identified. An analysis of all the responses revealed groups of glycopeptides with different response patterns that are of high interest for vaccination studies in CIA. Moreover, the SAR understanding obtained in this study provides a platform for the design of second-generation glycopeptides with tuned MHC affinities and T-cell responses.

  5. Intact glycopeptide characterization using mass spectrometry.

    Science.gov (United States)

    Cao, Li; Qu, Yi; Zhang, Zhaorui; Wang, Zhe; Prytkova, Iya; Wu, Si

    2016-05-01

    Glycosylation is one of the most prominent and extensively studied protein post-translational modifications. However, traditional proteomic studies at the peptide level (bottom-up) rarely characterize intact glycopeptides (glycosylated peptides without removing glycans), so no glycoprotein heterogeneity information is retained. Intact glycopeptide characterization, on the other hand, provides opportunities to simultaneously elucidate the glycan structure and the glycosylation site needed to reveal the actual biological function of protein glycosylation. Recently, significant improvements have been made in the characterization of intact glycopeptides, ranging from enrichment and separation, mass spectroscopy (MS) detection, to bioinformatics analysis. In this review, we recapitulated currently available intact glycopeptide characterization methods with respect to their advantages and limitations as well as their potential applications.

  6. ERK and PI3K regulate different aspects of the epithelial to mesenchymal transition of mammary tumor cells induced by truncated MUC1

    International Nuclear Information System (INIS)

    Horn, Galit; Gaziel, Avital; Wreschner, Daniel H.; Smorodinsky, Nechama I.; Ehrlich, Marcelo

    2009-01-01

    Epithelial to mesenchymal transition (EMT) integrates changes to cell morphology and signaling pathways resulting from modifications to the cell's transcriptional response. Different combinations of stimuli ignite this process in the contexts of development or tumor progression. The human MUC1 gene encodes multiple alternatively spliced forms of a polymorphic oncoprotein that is aberrantly expressed in epithelial malignancies. MUC1 is endowed with various signaling modules and has the potential to mediate proliferative and morphological changes characteristic of the progression of epithelial tumors. The tyrosine-rich cytoplasmic domain and the heavily glycosylated extracellular domain both play a role in MUC1-mediated signal transduction. However, the attribution of function to specific domains of MUC1 is difficult due to the concomitant presence of multiple forms of the protein, which stem from alternative splicing and proteolytic cleavage. Here we show that DA3 mouse mammary tumor cells stably transfected with a truncated genomic fragment of human MUC1 undergo EMT. In their EMT, these cells demonstrate altered [i] morphology, [ii] signaling pathways and [iii] expression of epithelial and mesenchymal markers. Similarly to well characterized human breast cancer cell lines, cells transfected with truncated MUC1 show an ERK-dependent increased spreading on fibronectin, and a PI3K-dependent enhancement of their proliferative rate.

  7. The Breast Cancer-Associated Glycoforms of MUC1, MUC1-Tn and sialyl-Tn, Are Expressed in COSMC Wild-Type Cells and Bind the C-Type Lectin MGL.

    Directory of Open Access Journals (Sweden)

    Richard Beatson

    Full Text Available Aberrant glycosylation occurs in the majority of human cancers and changes in mucin-type O-glycosylation are key events that play a role in the induction of invasion and metastases. These changes generate novel cancer-specific glyco-antigens that can interact with cells of the immune system through carbohydrate binding lectins. Two glyco-epitopes that are found expressed by many carcinomas are Tn (GalNAc-Ser/Thr and STn (NeuAcα2,6GalNAc-Ser/Thr. These glycans can be carried on many mucin-type glycoproteins including MUC1. We show that the majority of breast cancers carry Tn within the same cell and in close proximity to extended glycan T (Galβ1,3GalNAc the addition of Gal to the GalNAc being catalysed by the T synthase. The presence of active T synthase suggests that loss of the private chaperone for T synthase, COSMC, does not explain the expression of Tn and STn in breast cancer cells. We show that MUC1 carrying both Tn or STn can bind to the C-type lectin MGL and using atomic force microscopy show that they bind to MGL with a similar dead adhesion force. Tumour associated STn is associated with poor prognosis and resistance to chemotherapy in breast carcinomas, inhibition of DC maturation, DC apoptosis and inhibition of NK activity. As engagement of MGL in the absence of TLR triggering may lead to anergy, the binding of MUC1-STn to MGL may be in part responsible for some of the characteristics of STn expressing tumours.

  8. Synthesis of O-glycopeptides and construction of glycopeptide microarrays

    DEFF Research Database (Denmark)

    Blixt, Klas Ola; Cló, Emiliano

    2013-01-01

    O-glycosylation of proteins is an important modification which affects biological function and immunity. In this chapter, we provide protocols for efficient solid-phase O-glycopeptide synthesis (SPGPS) and protocols for the construction of glycopeptide microarray chips for screening applications....

  9. MicroRNA-128 suppresses paclitaxel-resistant lung cancer by inhibiting MUC1-C and BMI-1 in cancer stem cells.

    Science.gov (United States)

    Koh, Hyebin; Park, Hyeri; Chandimali, Nisansala; Huynh, Do Luong; Zhang, Jiao Jiao; Ghosh, Mrinmoy; Gera, Meeta; Kim, Nameun; Bak, Yesol; Yoon, Do-Young; Park, Yang Ho; Kwon, Taeho; Jeong, Dong Kee

    2017-12-15

    The existence of cancer stem cells (CSCs) is the main reason for failure of cancer treatment caused by drug resistance. Therefore, eradicating cancers by targeting CSCs remains a significant challenge. In the present study, because of the important role of BMI-1 proto-oncogene, polycomb ring finger (BMI-1) and C-terminal Mucin1 (MUC1-C) in tumor growth and maintenance of CSCs, we aimed to confirm that microRNA miR-128, as an inhibitor of BMI-1 and MUC1-C, could effectively suppress paclitaxel (PTX)-resistant lung cancer stem cells. We showed that CSCs have significantly higher expression levels of BMI-1, MUC1-C, stemness proteins, signaling factors, and higher malignancy compared with normal tumor cells. After transfection with miR-128, the BMI-1 and MUC1-C levels in CSCs were suppressed. When miR-128 was stably expressed in PTX-resistant lung cancer stem cells, the cells showed decreased proliferation, metastasis, self-renewal, migration, invasive ability, clonogenicity, and tumorigenicity in vitro and in vivo and increased apoptosis compared with miR-NC (negative control) CSCs. Furthermore, miR-128 effectively decreased the levels of β-catenin and intracellular signaling pathway-related factors in CSCs. MiR-128 also decreased the luciferase activity of MUC1 reporter constructs and reduced the levels of transmembrane MUC1-C and BMI-1. These results suggested miR-128 as an attractive therapeutic strategy for PTX-resistant lung cancer via inhibition of BMI-1 and MUC1-C.

  10. MUC1-C integrates PD-L1 induction with repression of immune effectors in non-small-cell lung cancer.

    Science.gov (United States)

    Bouillez, A; Rajabi, H; Jin, C; Samur, M; Tagde, A; Alam, M; Hiraki, M; Maeda, T; Hu, X; Adeegbe, D; Kharbanda, S; Wong, K-K; Kufe, D

    2017-07-13

    Immunotherapeutic approaches, particularly programmed death 1/programmed death ligand 1 (PD-1/PD-L1) blockade, have improved the treatment of non-small-cell lung cancer (NSCLC), supporting the premise that evasion of immune destruction is of importance for NSCLC progression. However, the signals responsible for upregulation of PD-L1 in NSCLC cells and whether they are integrated with the regulation of other immune-related genes are not known. Mucin 1 (MUC1) is aberrantly overexpressed in NSCLC, activates the nuclear factor-κB (NF-κB) p65→︀ZEB1 pathway and confers a poor prognosis. The present studies demonstrate that MUC1-C activates PD-L1 expression in NSCLC cells. We show that MUC1-C increases NF-κB p65 occupancy on the CD274/PD-L1 promoter and thereby drives CD274 transcription. Moreover, we demonstrate that MUC1-C-induced activation of NF-κB→︀ZEB1 signaling represses the TLR9 (toll-like receptor 9), IFNG, MCP-1 (monocyte chemoattractant protein-1) and GM-CSF genes, and that this signature is associated with decreases in overall survival. In concert with these results, targeting MUC1-C in NSCLC tumors suppresses PD-L1 and induces these effectors of innate and adaptive immunity. These findings support a previously unrecognized central role for MUC1-C in integrating PD-L1 activation with suppression of immune effectors and poor clinical outcome.

  11. Cancer-associated autoantibodies to MUC1 and MUC4--a blinded case–control study of colorectal cancer in UK collaborative trial of ovarian cancer screening

    DEFF Research Database (Denmark)

    Pedersen, Johannes W; Gentry-Maharaj, Aleksandra; Nøstdal, Alexander

    2014-01-01

    of colorectal cancer diagnosis and healthy controls. Subsequently, the selected biomarkers were evaluated in a blinded nested case–control study using stored serum samples from among the 50,640 women randomized to the multimodal arm of the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS), where......, at 95% specificity. IgA to MUC4 glycoforms were unable to discriminate between cases and controls in the UKCTOCS sera. Additional analysis was undertaken by combining the data of MUC1-STn and MUC1-Core3 with previously generated data on autoantibodies to p53 peptides, which increased the sensitivity...

  12. The Breast Cancer-Associated Glycoforms of MUC1, MUC1-Tn and sialyl-Tn, Are Expressed in COSMC Wild-Type Cells and Bind the C-Type Lectin MGL

    DEFF Research Database (Denmark)

    Beatson, Richard; Maurstad, Gjertrud; Picco, Gianfranco

    2015-01-01

    Aberrant glycosylation occurs in the majority of human cancers and changes in mucin-type O-glycosylation are key events that play a role in the induction of invasion and metastases. These changes generate novel cancer-specific glyco-antigens that can interact with cells of the immune system through...... carbohydrate binding lectins. Two glyco-epitopes that are found expressed by many carcinomas are Tn (GalNAc-Ser/Thr) and STn (NeuAcα2,6GalNAc-Ser/Thr). These glycans can be carried on many mucin-type glycoproteins including MUC1. We show that the majority of breast cancers carry Tn within the same cell...

  13. Purification of MUC1 from Bovine Milk-Fat Globules and Characterization of a Corresponding Full-Length cDNA Clone

    DEFF Research Database (Denmark)

    Pallesen, Lone Tjener; Andersen, Mikkel Holmen; Nielsen, Rune

    2001-01-01

    acid sequences obtained by peptide mapping. The complete amino acid sequence of MUC1 was determined by cloning and sequencing the corresponding bovine mammary gland cDNA, which was shown to encode a protein of 580 amino acid residues comprising a cleavable signal peptide of 22 residues. The deduced...

  14. Single molecule real time sequencing in ADTKD-MUC1 allows complete assembly of the VNTR and exact positioning of causative mutations

    NARCIS (Netherlands)

    Wenzel, Andrea; Altmueller, Janine; Ekici, Arif B.; Popp, Bernt; Stueber, Kurt; Thiele, Holger; Pannes, Alois; Staubach, Simon; Salido, Eduardo; Nuernberg, Peter; Reinhardt, Richard; Reis, Andre; Rump, Patrick; Hanisch, Franz-Georg; Wolf, Matthias T. F.; Wiesener, Michael; Huettel, Bruno; Beck, Bodo B.

    2018-01-01

    Recently, the Mucin-1 (MUC1) gene has been identified as a causal gene of autosomal dominant tubulointerstitial kidney disease (ADTKD). Most causative mutations are buried within a GC-rich 60 basepair variable number of tandem repeat (VNTR), which escapes identification by massive parallel

  15. Mucin architecture behind the immune response : Design, evaluation and conformational analysis of an antitumor vaccine derived from an unnatural MUC1 fragment

    NARCIS (Netherlands)

    Martínez-Sáez, Nuria; Supekar, Nitin T.; Wolfert, Margreet A.; Bermejo, Iris A.; Hurtado-Guerrero, Ramón; Asensio, Juan L.; Jiménez-Barbero, Jesús; Busto, Jesús H.; Avenoza, Alberto; Boons, Geert Jan; Peregrina, Jesús M.; Corzana, Francisco

    2016-01-01

    A tripartite cancer vaccine candidate, containing a quaternary amino acid (α-methylserine) in the most immunogenic domain of MUC1, has been synthesized and examined for antigenic properties in transgenic mice. The vaccine which is glycosylated with GalNAc at the unnatural amino acid, was capable of

  16. Acquired resistance to HSP90 inhibitor 17-AAG and increased metastatic potential are associated with MUC1 expression in colon carcinoma cells.

    Science.gov (United States)

    Liu, Xin; Ban, Li-Li; Luo, Gang; Li, Zhi-Yao; Li, Yun-Feng; Zhou, Yong-Chun; Wang, Xi-Cai; Jin, Cong-Guo; Ye, Jia-Gui; Ma, Ding-Ding; Xie, Qing; Huang, You-Guang

    2016-06-01

    Heat shock protein 90 (HSP90) is a molecular chaperone required for the stability and function of many proteins. The chaperoning of oncoproteins by HSP90 enhances the survival, growth, and invasive potential of cancer cells. HSP90 inhibitors are promising new anticancer agents, in which the benzoquinone ansamycin 17-allylamino-17-demethoxygeldanamycin (17-AAG) is currently in clinical evaluation. However, the implications of acquired resistance to this class of drug remain largely unexplored. In the present study, we have generated isogenic human colon cancer cell lines that are resistant to 17-AAG by continued culturing in the compound. Cross-resistance was found with another HSP90 inhibitor 17-dimethylaminoethylamino-17-demethoxygeldanamycin. The resistant cells showed obvious morphology changes with a metastatic phenotype and significant increases in migration and adhesion to collagens. Western blotting analysis of epithelial-mesenchymal transition molecular markers found that expression of E-cadherin downregulated, whereas expression of N-cadherin and β-catenin upregulated in the resistant cells. Mucin 1 (MUC1) has been reported to mediate metastasis as well as chemical resistance in many cancers. Here, we found that MUC1 expression was significantly elevated in the acquired drug resistance cells. 17-AAG treatment could decrease MUC1 more in parental cells than in acquired 17-AAG-resistant cells. Further study found that knockdown of MUC1 expression by small interfering RNA could obviously re-sensitize the resistant cells to 17-AAG treatment, and decrease the cell migration and adhesion. These were coupled with a downregulation in N-cadherin and β-catenin. The results indicate that HSP90 inhibitor therapies in colon carcinomas could generate resistance and increase metastatic potential that might mediated by upregulation of MUC1 expression. Findings from this study further our understanding of the potential clinical effects of HSP90-directed therapies in

  17. Old and New Glycopeptide Antibiotics: Action and Resistance

    OpenAIRE

    Binda, Elisa; Marinelli, Flavia; Marcone, Giorgia Letizia

    2014-01-01

    Glycopeptides are considered antibiotics of last resort for the treatment of life-threatening infections caused by relevant Gram-positive human pathogens, such as Staphylococcus aureus, Enterococcus spp. and Clostridium difficile. The emergence of glycopeptide-resistant clinical isolates, first among enterococci and then in staphylococci, has prompted research for second generation glycopeptides and a flurry of activity aimed at understanding resistance mechanisms and their evolution. Glycop...

  18. Sulfated glycopeptide nanostructures for multipotent protein activation

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Sungsoo S.; Fyrner, Timmy; Chen, Feng; Álvarez, Zaida; Sleep, Eduard; Chun, Danielle S.; Weiner, Joseph A.; Cook, Ralph W.; Freshman, Ryan D.; Schallmo, Michael S.; Katchko, Karina M.; Schneider, Andrew D.; Smith, Justin T.; Yun, Chawon; Singh, Gurmit; Hashmi, Sohaib Z.; McClendon, Mark T.; Yu, Zhilin; Stock, Stuart R.; Hsu, Wellington K.; Hsu, Erin L.; Stupp , Samuel I. (NWU)

    2017-06-19

    Biological systems have evolved to utilize numerous proteins with capacity to bind polysaccharides for the purpose of optimizing their function. A well-known subset of these proteins with binding domains for the highly diverse sulfated polysaccharides are important growth factors involved in biological development and tissue repair. We report here on supramolecular sulfated glycopeptide nanostructures, which display a trisulfated monosaccharide on their surfaces and bind five critical proteins with different polysaccharide-binding domains. Binding does not disrupt the filamentous shape of the nanostructures or their internal β-sheet backbone, but must involve accessible adaptive configurations to interact with such different proteins. The glycopeptide nanostructures amplified signalling of bone morphogenetic protein 2 significantly more than the natural sulfated polysaccharide heparin, and promoted regeneration of bone in the spine with a protein dose that is 100-fold lower than that required in the animal model. These highly bioactive nanostructures may enable many therapies in the future involving proteins.

  19. The Construction of Chimeric T-Cell Receptor with Spacer Base of Modeling Study of VHH and MUC1 Interaction

    Directory of Open Access Journals (Sweden)

    Nazanin Pirooznia

    2011-01-01

    Full Text Available Adaptive cell immunotherapy with the use of chimeric receptors leads to the best and most specific response against tumors. Chimeric receptors consist of a signaling fragment, extracellular spacer, costimulating domain, and an antibody. Antibodies cause immunogenicity; therefore, VHH is a good replacement for ScFv in chimeric receptors. Since peptide sequences have an influence on chimeric receptors, the effect of peptide domains on each other's conformation were investigated. CD3Zeta, CD28, VHH and CD8α, and FcgIIα are used as signaling moieties, costimulating domain, antibody, and spacers, respectively. To investigate the influence of the ligation of spacers on the conformational structure of VHH, models of VHH were constructed. Molecular dynamics simulation was run to study the influence of the presence of spacers on the conformational changes in the binding sites of VHH. Root mean square deviation and root mean square fluctuation of critical segments in the binding site showed no noticeable differences with those in the native VHH. Results from molecular docking revealed that the presence of spacer FcgIIα causes an increasing effect on VHH with MUC1 interaction. Each of the constructs was transformed into the Jurkat E6.1. Expression analysis and evaluation of their functions were examined. The results showed good expression and function.

  20. MUC1 gene polymorphism in three Nelore lines selected for growth and its association with growth and carcass traits.

    Science.gov (United States)

    de Souza, Fabio Ricardo Pablos; Maione, Sandra; Sartore, Stefano; Soglia, Dominga; Spalenza, Veronica; Cauvin, Elsa; Martelli, Lucia Regina; Mercadante, Maria Eugênia Zerlotti; Sacchi, Paola; de Albuquerque, Lucia Galvão; Rasero, Roberto

    2012-02-01

    The objective of this study was to describe the VNTR polymorphism of the mucin 1 gene (MUC1) in three Nelore lines selected for yearling weight to determine whether allele and genotype frequencies of this polymorphism were affected by selection for growth. In addition, the effects of the polymorphism on growth and carcass traits were evaluated. Birth, weaning and yearling weights, rump height, Longissimus muscle area, backfat thickness, and rump fat thickness, were analyzed. A total of 295 Nelore heifers from the Beef Cattle Research Center, Instituto de Zootecnia de Sertãozinho, were used, including 41 of the control line, 102 of the selection line and 152 of the traditional. The selection and traditional lines comprise animals selected for higher yearling weight, whereas control line animals are selected for yearling weight close to the average. Five alleles were identified, with allele 1 being the most frequent in the three lines, especially in the lines selected for higher means for yearling weight. Heterozygosity was significantly higher in the control line. Association analyses showed significant effects of allele 1 on birth weight and weaning weight while the allele 3 exert significant effects on yearling weight and back fat thickness. Despite these findings, application of this marker to marker-assisted selection requires more consistent results based on the genotyping of a larger number of animals in order to increase the accuracy of the statistical analyses.

  1. Titanium dioxide enrichment of sialic acid-containing glycopeptides

    DEFF Research Database (Denmark)

    Palmisano, Giuseppe; Lendal, Sara E; Larsen, Martin Røssel

    2011-01-01

    the glycosylation site of N-linked sialylated glycoproteins. The method relies on the specificity of titanium dioxide affinity chromatography to isolate sialic acid-containing glycopeptides. After enzymatic release of the glycans, the enriched sialylated glycopeptides are analyzed by mass spectrometry...

  2. Synthetic glycopeptides and glycoproteins with applications in biological research

    Directory of Open Access Journals (Sweden)

    Ulrika Westerlind

    2012-05-01

    Full Text Available Over the past few years, synthetic methods for the preparation of complex glycopeptides have been drastically improved. The need for homogenous glycopeptides and glycoproteins with defined chemical structures to study diverse biological phenomena further enhances the development of methodologies. Selected recent advances in synthesis and applications, in which glycopeptides or glycoproteins serve as tools for biological studies, are reviewed. The importance of specific antibodies directed to the glycan part, as well as the peptide backbone has been realized during the development of synthetic glycopeptide-based anti-tumor vaccines. The fine-tuning of native chemical ligation (NCL, expressed protein ligation (EPL, and chemoenzymatic glycosylation techniques have all together enabled the synthesis of functional glycoproteins. The synthesis of structurally defined, complex glycopeptides or glyco-clusters presented on natural peptide backbones, or mimics thereof, offer further possibilities to study protein-binding events.

  3. A bioinformatics prediction approach towards analyzing the glycosylation, co-expression and interaction patterns of epithelial membrane antigen (EMA/MUC1)

    Energy Technology Data Exchange (ETDEWEB)

    Kalra, Rajkumar S., E-mail: renu-wadhwa@aist.go.jp; Wadhwa, Renu, E-mail: renu-wadhwa@aist.go.jp [Cell Proliferation Research Group and DBT-AIST International Laboratory for Advanced Biomedicine, National Institute of Advanced Industrial Science and Technology (AIST Central 4), 1-1-1 Higashi, Tsukuba, Ibaraki 305-8562 (Japan)

    2015-02-27

    Epithelial membrane antigen (EMA or MUC1) is a heavily glycosylated, type I transmembrane glycoprotein commonly expressed by epithelial cells of duct organs. It has been shown to be aberrantly glycosylated in several diseases including cancer. Protein sequence based annotation and analysis of glycosylation profile of glycoproteins by robust computational and comprehensive algorithms provides possible insights to the mechanism(s) of anomalous glycosylation. In present report, by using a number of bioinformatics applications we studied EMA/MUC1 and explored its trans-membrane structural domain sequence that is widely subjected to glycosylation. Exploration of different extracellular motifs led to prediction of N and O-linked glycosylation target sites. Based on the putative O-linked target sites, glycosylated moieties and pathways were envisaged. Furthermore, Protein network analysis demonstrated physical interaction of EMA with a number of proteins and confirmed its functional involvement in cell growth and proliferation pathways. Gene Ontology analysis suggested an involvement of EMA in a number of functions including signal transduction, protein binding, processing and transport along with glycosylation. Thus, present study explored potential of bioinformatics prediction approach in analyzing glycosylation, co-expression and interaction patterns of EMA/MUC1 glycoprotein.

  4. A bioinformatics prediction approach towards analyzing the glycosylation, co-expression and interaction patterns of epithelial membrane antigen (EMA/MUC1)

    International Nuclear Information System (INIS)

    Kalra, Rajkumar S.; Wadhwa, Renu

    2015-01-01

    Epithelial membrane antigen (EMA or MUC1) is a heavily glycosylated, type I transmembrane glycoprotein commonly expressed by epithelial cells of duct organs. It has been shown to be aberrantly glycosylated in several diseases including cancer. Protein sequence based annotation and analysis of glycosylation profile of glycoproteins by robust computational and comprehensive algorithms provides possible insights to the mechanism(s) of anomalous glycosylation. In present report, by using a number of bioinformatics applications we studied EMA/MUC1 and explored its trans-membrane structural domain sequence that is widely subjected to glycosylation. Exploration of different extracellular motifs led to prediction of N and O-linked glycosylation target sites. Based on the putative O-linked target sites, glycosylated moieties and pathways were envisaged. Furthermore, Protein network analysis demonstrated physical interaction of EMA with a number of proteins and confirmed its functional involvement in cell growth and proliferation pathways. Gene Ontology analysis suggested an involvement of EMA in a number of functions including signal transduction, protein binding, processing and transport along with glycosylation. Thus, present study explored potential of bioinformatics prediction approach in analyzing glycosylation, co-expression and interaction patterns of EMA/MUC1 glycoprotein

  5. Old and New Glycopeptide Antibiotics: Action and Resistance

    Directory of Open Access Journals (Sweden)

    Elisa Binda

    2014-11-01

    Full Text Available Glycopeptides are considered antibiotics of last resort for the treatment of life-threatening infections caused by relevant Gram-positive human pathogens, such as Staphylococcus aureus, Enterococcus spp. and Clostridium difficile. The emergence of glycopeptide-resistant clinical isolates, first among enterococci and then in staphylococci, has prompted research for second generation glycopeptides and a flurry of activity aimed at understanding resistance mechanisms and their evolution. Glycopeptides are glycosylated non-ribosomal peptides produced by a diverse group of soil actinomycetes. They target Gram-positive bacteria by binding to the acyl-D-alanyl-D-alanine (D-Ala-D-Ala terminus of the growing peptidoglycan on the outer surface of the cytoplasmatic membrane. Glycopeptide-resistant organisms avoid such a fate by replacing the D-Ala-D-Ala terminus with D-alanyl-D-lactate (D-Ala-D-Lac or D-alanyl-D-serine (D-Ala-D-Ser, thus markedly reducing antibiotic affinity for the cellular target. Resistance has manifested itself in enterococci and staphylococci largely through the expression of genes (named van encoding proteins that reprogram cell wall biosynthesis and, thus, evade the action of the antibiotic. These resistance mechanisms were most likely co-opted from the glycopeptide producing actinomycetes, which use them to avoid suicide during antibiotic production, rather than being orchestrated by pathogen bacteria upon continued treatment. van-like gene clusters, similar to those described in enterococci, were in fact identified in many glycopeptide-producing actinomycetes, such as Actinoplanes teichomyceticus, which produces teicoplanin, and Streptomyces toyocaensis, which produces the A47934 glycopeptide. In this paper, we describe the natural and semi-synthetic glycopeptide antibiotics currently used as last resort drugs for Gram-positive infections and compare the van gene-based strategies of glycopeptide resistance among the pathogens and

  6. Phase I dose escalation pharmacokinetic assessment of intravenous humanized anti-MUC1 antibody AS1402 in patients with advanced breast cancer.

    Science.gov (United States)

    Pegram, Mark D; Borges, Virginia F; Ibrahim, Nuhad; Fuloria, Jyotsna; Shapiro, Charles; Perez, Susan; Wang, Karen; Schaedli Stark, Franziska; Courtenay Luck, Nigel

    2009-01-01

    MUC1 is a cell-surface glycoprotein that establishes a molecular barrier at the epithelial surface and engages in morphogenetic signal transduction. Alterations in MUC1 glycosylation accompany the development of cancer and influence cellular growth, differentiation, transformation, adhesion, invasion, and immune surveillance. A 20-amino-acid tandem repeat that forms the core protein of MUC1 is overexpressed and aberrantly glycosylated in the majority of epithelial tumors. AS1402 (formerly R1550) is a humanized IgG1k monoclonal antibody that binds to PDTR sequences within this tandem repeat that are not exposed in normal cells. AS1402 is a potent inducer of antibody-dependent cellular cytotoxicity (ADCC), specifically against MUC1-expressing tumor cells. The objective of this study was to determine the safety, tolerability, and pharmacokinetic (PK) characteristics of AS1402 monotherapy in patients with locally advanced or metastatic MUC1-positive breast cancer that had progressed after anthracyclines- and taxane-based therapy. Patients received AS1402 over a 1- to 3-hour intravenous (i.v.) infusion at doses between 1 and 16 mg/kg, with repeated dosing every 1 to 3 weeks (based on patient-individualized PK assessment) until disease progression. Serum AS1402 levels were measured at multiple times after i.v. administration. Human anti-human antibody (HAHA) responses were measured to determine the immunogenicity of AS1402. Noncompartmental pharmacokinetic parameters were determined and were used to assess dose dependency across the dose range studied. Twenty-six patients were treated. AS1402 was generally well tolerated. Two grade 3/4 drug-related adverse events were reported, both at the 3-mg/kg dose. Neither was observed in expanded or subsequent dosing cohorts. No anti-human antibodies were detected. Plasma concentrations of AS1402 appeared to be proportional to dose within the 1- to 16-mg/kg dose range assessed, with a mean terminal half-life of 115.4 +/- 37.1 hours

  7. Synthetic Self-Adjuvanting Glycopeptide Cancer Vaccines

    Science.gov (United States)

    Payne, Richard; McDonald, David; Byrne, Scott

    2015-10-01

    Due to changes in glycosyltransferase expression during tumorigenesis, the glycoproteins of cancer cells often carry highly truncated carbohydrate chains compared to those on healthy cells. These glycans are known as tumor-associated carbohydrate antigens, and are prime targets for use in vaccines for the prevention and treatment of cancer. Herein, we review the state-of-the-art in targeting the immune system towards tumor-associated glycopeptide antigens via synthetic self adjuvanting vaccines, in which the antigenic and adjuvanting moieties of the vaccines are present in the same molecule. The majority of the self-adjuvanting glycopeptide cancer vaccines reported to date employ antigens from mucin 1, a protein which is highly over-expressed and aberrantly glycosylated in many forms of cancer. The adjuvants used in these vaccines predominantly include lipopeptide- or lipoamino acid-based TLR2 agonists, although studies investigating stimulation of TLR9 and TLR4 are also discussed. Most of these adjuvants are highly lipophilic, and, upon conjugation to antigenic peptides, provide amphiphilic vaccine molecules. The amphiphilic nature of these vaccine constructs can lead to the formation of higher-order structures by vaccines in solution, which are likely to be important for their efficacy in vivo.

  8. Relação entre a expressão da MUC1 e os estadiamentos TNM e Astler-Coller no câncer colorretal Relation between the expression of MUC1 and TNM and Astler-Coller staging systems in colorectal cancer

    Directory of Open Access Journals (Sweden)

    Paula Gabriela Melo Morais

    2008-06-01

    Full Text Available A expressão de marcadores tumorais que se correlacionam com a agressividade dos cânceres vem sendo investigada com vigor. Tendo o câncer colorretal significativa incidência, biomarcadores que possam avaliá-lo quanto a esse aspecto, não são exceção nesta investigação. OBJETIVO: estabelecer a relação entre agressividade do câncer colorretal de acordo com os estadiamentos TNM e Astler-Coller e a expressão da Mucina1 (MUC1 em uma determinada amostra de tumores. METODOLOGIA: foram examinados 36 cânceres colorretais ressecados pelos coloproctologistas do Hospital Universitário da UFAL quanto à presença de uma reação imuno-histoquímica positiva para MUC1 em padrão citoplasmático. Em seguida, correlacionou-se esta com os estádios dos tumores. RESULTADOS: A imunoexpressão da MUC1 ocorreu em 50% dos casos. Destes, 61% estavam entre os estádios T3 e T4; 39% entre N1 e N2; todos os casos do estudo eram M0; e 40% encontravam-se entre os estádios C1 e C3 de Astler-Coller. Avaliada a positividade por cada estádio em separado, percebeu-se que estes aumentaram proporcionalmente, principalmente em relação aos estadios "N" e Astler-Coller. CONCLUSÃO: a ausência da reatividade imuno-histoquímica à MUC1 não excluiu a possibilidade de evolução para um estadio avançado. Porém, sua presença denota a evolução do câncer colorretal para estádios mais agressivos.The expression of tumor markers that correlates with the aggressiveness of cancers has been strongly investigated. Having colorectal cancer a significant incidence, biomarkers that can evaluate it concerning this aspect are not an exception in this inquiry. AIM: To establish a relation between aggressiveness of colorectal cancer according to TNM and Astler-Coller staging systems and the expression of Mucin1 (MUC1 in a determined sample of tumors. METHODS: 36 colorectal cancers resected by proctologists of the University Hospital of UFAL were examined regarding the

  9. Utilizing ion-pairing hydrophilic interaction chromatography solid phase extraction for efficient glycopeptide enrichment in glycoproteomics

    DEFF Research Database (Denmark)

    Mysling, Simon; Palmisano, Giuseppe; Højrup, Peter

    2010-01-01

    Glycopeptide enrichment is a prerequisite to enable structural characterization of protein glycosylation in glycoproteomics. Here we present an improved method for glycopeptide enrichment based on zwitter-ionic hydrophilic interaction chromatography solid phase extraction (ZIC-HILIC SPE...

  10. Random glycopeptide bead libraries for seromic biomarker discovery

    DEFF Research Database (Denmark)

    Kracun, Stjepan Kresimir; Cló, Emiliano; Clausen, Henrik

    2010-01-01

    have developed a random glycopeptide bead library screening platform for detection of autoantibodies and other binding proteins. Libraries were build on biocompatible PEGA beads including a safety-catch C-terminal amide linker (SCAL) that allowed mild cleavage conditions (I(2)/NaBH(4) and TFA...... to other tumor glycoforms by on-bead enzymatic glycosylation reactions with recombinant glycosyltransferases. Hence, we have developed a high-throughput flexible platform for rapid discovery of O-glycopeptide biomarkers and the method has applicability in other types of assays such as lectin...

  11. Associations of genetic variants in the PSCA, MUC1 and PLCE1 genes with stomach cancer susceptibility in a Chinese population.

    Directory of Open Access Journals (Sweden)

    Hongwei Sun

    Full Text Available Several genetic variants including PSCA rs2294008 C>T and rs2976392 G>A, MUC1 rs4072037 T>C, and PLCE1 rs2274223 A>G have shown significant association with stomach cancer risk in the previous genome-wide association studies (GWASs.To evaluate associations of these SNPs in the Han Chinese, an independent hospital based case-control study was performed by genotyping these four polymorphisms in a total of 692 stomach cancer cases and 774 healthy controls acquired by using frequency matching for age and gender. False-positive report probability (FPRP analysis was also performed to validate all statistically significant findings.In the current study, significant association with stomach cancer susceptibility was observed for all the four polymorphisms of interest. Specifically, a significant increased stomach cancer risk was associated with PSCA rs2294008 (CT vs. CC: adjusted OR = 1.37, 95% CI = 1.07-1.74, and CT/TT vs.CC: adjusted OR = 1.30, 95% CI = 1.03-1.63, PSCA rs2976392 (AG vs. GG: adjusted OR = 1.30, 95% CI = 1.02-1.65, and AG/AA vs. GG: adjusted OR = 1.26, 95% CI = 1.00-1.59, or PLCE1 rs2274223 (AG vs. AA: adjusted OR = 1.48, 95% CI = 1.15-1.90, and AG/GG vs. AA: adjusted OR = 1.45, 95% CI = 1.14-1.84, respectively. In contrast, MUC1 rs4072037 was shown to decrease the cancer risk (CT vs. TT: adjusted OR = 0.77, 95% CI = 0.60-0.98. Patients with more than one risk genotypes had significant increased risk to develop stomach cancer (adjusted OR = 1.30, 95% CI = 1.03-1.64, when compared with those having 0-1 risk genotypes. Stratified analysis indicated that the increased risk was more pronounced in younger subjects, men, ever smokers, smokers with pack years ≤ 27, patients with high BMI, or non-cardia stomach cancer.This study substantiated the associations between four previous reported genetic variants and stomach cancer susceptibility in an independent Han Chinese population. Further studies with larger sample size and different

  12. Intratumoral delivery of CpG-conjugated anti-MUC1 antibody enhances NK cell anti-tumor activity.

    Science.gov (United States)

    Schettini, Jorge; Kidiyoor, Amritha; Besmer, Dahlia M; Tinder, Teresa L; Roy, Lopamudra Das; Lustgarten, Joseph; Gendler, Sandra J; Mukherjee, Pinku

    2012-11-01

    Monoclonal antibodies (mAbs) against tumor-associated antigens are useful anticancer agents. Antibody-dependent cellular cytotoxicity (ADCC) is one of the major mechanisms responsible for initiating natural killer cell (NK)-mediated killing of tumors. However, the regulation of ADCC via NK cells is poorly understood. We have investigated the cytolytic activity of NK cells against pancreatic cancer cells that were coated with an antibody directed against the human tumor antigen, Mucin-1 designated HMFG-2, either alone or conjugated to CpG oligodeoxynucleotide (CpG ODN). Conjugated antibodies were tested for their ability to elicit ADCC in vitro and in vivo against pancreatic cancer cells. NK cells cultured in the presence of immobilized CpG ODN, HMFG-2 Ab, or CpG ODN-conjugated HMFG-2 Ab were able to up-regulate perforin similarly. Interestingly, a significant higher ADCC was observed when CpG ODN-conjugated HMFG-2-coated tumor cells were co-cultured with NK cells compared to unconjugated HMFG-2 Ab or CpG ODN alone. Moreover, MyD88-deficient NK cells can perform ADCC in vitro. Furthermore, intratumoral injections of CpG ODN-conjugated HMFG-2 induced a significant reduction in tumor burden in vivo in an established model of pancreatic tumor in nude mice compared to CpG ODN or the HMFG-2 alone. Depletion of macrophages or NK cells before treatment confirmed that both cells were required for the anti-tumor response in vivo. Results also suggest that CpG ODN and HMFG-2 Ab could be sensed by NK cells on the mAb-coated tumor cells triggering enhanced ADCC in vitro and in vivo.

  13. Feasibility study of Anti-MUC1 aptamer use as vector target director of 1,10 phenantrolin for radiosensitization of breast cancer cells

    International Nuclear Information System (INIS)

    Alves, Laís Nascimento

    2017-01-01

    With the rising incidence of cancer and this disease as global public health dilemma, there is an alarming need of studying new cancer therapies. To achieve the development of efficient agents is essential to understand the fundamental mechanisms of carcinogenesis and tumor progression. Overexpression of proteins in malignant tissues, in contrast to expression of the proteins found in normal tissues of the same organ, is crucially important and of great interest for the characterization of potential tumor biomarkers. Following this premise, MUC1 glycoprotein was selected as a therapeutic target in a breast cancer model. In order to determine the viability of the aptA aptamer as radiosensitizers carrier, the toxic compound 1,10 phenanthroline, complexed with Fe(II) was intercalated in the aptamers. The dissociation constant was found at a value of Kd = 30 μM. The selective binding and internalization of the compound was demonstrated. Based on these data, the aptA can be used as carrying vector of molecules such as 1,10-phenanthroline. As a next stage, the evaluation of its in vitro potential as radiosensitizers with the use of ionizing radiation will be done. (author)

  14. Analysis of O-Glycopeptides by Acetone Enrichment and Capillary Electrophoresis-Mass Spectrometry.

    Science.gov (United States)

    Mancera-Arteu, Montserrat; Giménez, Estela; Benavente, Fernando; Barbosa, José; Sanz-Nebot, Victòria

    2017-11-03

    Acetone precipitation was evaluated as a rapid, simple, low-cost, and efficient method for the selective purification of O-glycopeptides from enzymatic digests of glycoproteins. Ovalbumin (OVA), human and bovine α 1 -acid glycoprotein (hAGP and bAGP), human apolipoprotein C-III (APO-C3), and recombinant human erythropoietin (rhEPO) were used to obtain enzymatic digests with a broad and varied set of peptides, N-glycopeptides, and O-glycopeptides. After digestion and before capillary electrophoresis mass spectrometry (CE-MS) analysis, the amount of ice-cold acetone added to the digests was optimized to maximize recoveries of O-glycopeptides. Furthermore, the different behavior of peptides, N- and O-glycopeptides was explained by studying with multivariate data analysis methods the influence of several physicochemical parameters and properties related to their composition and structure. Principal component analysis (PCA) and, afterward, partial least-squares discriminant analysis (PLS-DA) were used to identify the most significant variables and their importance to differentiate between peptides, N-glycopeptides and O-glycopeptides, or within these classes. This information was useful to understand precipitation of these compounds after addition of acetone and for the selection of the optimal conditions for purification of specific O-glycopeptide biomarkers. Special attention was paid to O 126 -glycopeptide glycoforms of rhEPO because of their applicability in biopharmaceutical quality control and doping analysis.

  15. Antigiardial activity of glycoproteins and glycopeptides from Ziziphus honey.

    Science.gov (United States)

    Mohammed, Seif Eldin A; Kabashi, Ahmed S; Koko, Waleed S; Azim, M Kamran

    2015-01-01

    Natural honey contains an array of glycoproteins, proteoglycans and glycopeptides. Size-exclusion chromatography fractionated Ziziphus honey proteins into five peaks with molecular masses in the range from 10 to >200 kDa. The fractionated proteins exhibited in vitro activities against Giardia lamblia with IC50 values ≤ 25 μg/mL. Results indicated that honey proteins were more active as antiprotozoal agents than metronidazole. This study indicated the potential of honey proteins and peptides as novel antigiardial agents.

  16. Glycopeptide dendrimers, Part III – a review: Use of glycopeptide dendrimers in immunotherapy and diagnosis of cancer and viral diseases

    Czech Academy of Sciences Publication Activity Database

    Niederhafner, Petr; Reiniš, Milan; Šebestík, Jaroslav; Ježek, Jan

    2008-01-01

    Roč. 14, č. 5 (2008), s. 556-587 ISSN 1075-2617 R&D Projects: GA MZe QF3115; GA ČR GA203/03/1362; GA ČR GA203/07/1517; GA AV ČR KAN200520703 Institutional research plan: CEZ:AV0Z40550506; CEZ:AV0Z50520514 Keywords : glycoconjugates * glycodendrimers * glycopeptides * anticancer vaccines * antiviral vaccines Subject RIV: CC - Organic Chemistry Impact factor: 1.654, year: 2008

  17. Pretargeting of human mammary carcinoma xenografts with bispecific anti-MUC1/anti-Ga chelate antibodies and immunoscintigraphy with PET

    International Nuclear Information System (INIS)

    Schuhmacher, Jochen; Klivenyi, Gabor; Kaul, Sepp; Henze, Marcus; Matys, Ronald; Hauser, Harald; Clorius, John

    2001-01-01

    We recently demonstrated the feasibility of combining enhanced tumor-to-tissue contrast and PET imaging for immunoscintigraphic tumor localization in pancreas and colon carcinoma bearing nude mice. Contrast enhancement was obtained with a multistep targeting technique that consists of the sequential administration of an antitumor/antihapten bispecific antibody (BS-MAb), a blocker to saturate the antihapten binding sites of the BS-MAb that remains in circulation, and a low molecular weight Ga chelate, labeled with the positron emitter 68 Ga, which serves as the hapten. To evaluate the efficacy of this pretargeting technique for breast cancer localization, we synthesized a BS-MAb from the F(ab') 2 fragments of the anti-MUC1 MAb 12H12 which reacts with the vast majority of human breast carcinomas, and the F(ab') fragment of an anti-Ga chelate MAb using a bifunctional chemical linker. The BS-MAb was tested for its affinity and its biokinetics in nude mice bearing a human mammary carcinoma. Equilibrium binding of the BS-MAb for mammary carcinoma cells was low (1.2 x 10 7 M -1 ) while the binding capacity of cells was high (8.4 x 10 6 BS-MAbs per cell). Tumor uptake of the 67 Ga labeled chelate in pretargeted animals was to 5.8 ± 0.8% iD/g resulting in a tumor-to-blood ratio of 2.6 at 1h postinjection. This compares with a ratio of 0.65 and 0.85 obtained with 125 I-labeled native 12H12 at 24h and 48h postinjection. No difference in the tumor uptake of both the 68 Ga and 67 Ga labeled chelate was observed. PET imaging of mice, started 1h postinjection of the 68 Ga chelate, clearly visualized all tumors

  18. Pretargeting of human mammary carcinoma xenografts with bispecific anti-MUC1/anti-Ga chelate antibodies and immunoscintigraphy with PET

    Energy Technology Data Exchange (ETDEWEB)

    Schuhmacher, Jochen; Klivenyi, Gabor; Kaul, Sepp; Henze, Marcus; Matys, Ronald; Hauser, Harald; Clorius, John

    2001-10-01

    We recently demonstrated the feasibility of combining enhanced tumor-to-tissue contrast and PET imaging for immunoscintigraphic tumor localization in pancreas and colon carcinoma bearing nude mice. Contrast enhancement was obtained with a multistep targeting technique that consists of the sequential administration of an antitumor/antihapten bispecific antibody (BS-MAb), a blocker to saturate the antihapten binding sites of the BS-MAb that remains in circulation, and a low molecular weight Ga chelate, labeled with the positron emitter {sup 68}Ga, which serves as the hapten. To evaluate the efficacy of this pretargeting technique for breast cancer localization, we synthesized a BS-MAb from the F(ab'){sub 2} fragments of the anti-MUC1 MAb 12H12 which reacts with the vast majority of human breast carcinomas, and the F(ab') fragment of an anti-Ga chelate MAb using a bifunctional chemical linker. The BS-MAb was tested for its affinity and its biokinetics in nude mice bearing a human mammary carcinoma. Equilibrium binding of the BS-MAb for mammary carcinoma cells was low (1.2 x 10{sup 7} M{sup -1}) while the binding capacity of cells was high (8.4 x 10{sup 6} BS-MAbs per cell). Tumor uptake of the {sup 67}Ga labeled chelate in pretargeted animals was to 5.8 {+-} 0.8% iD/g resulting in a tumor-to-blood ratio of 2.6 at 1h postinjection. This compares with a ratio of 0.65 and 0.85 obtained with {sup 125}I-labeled native 12H12 at 24h and 48h postinjection. No difference in the tumor uptake of both the {sup 68}Ga and {sup 67}Ga labeled chelate was observed. PET imaging of mice, started 1h postinjection of the {sup 68}Ga chelate, clearly visualized all tumors.

  19. Study on behaviors and performances of universal N-glycopeptide enrichment methods.

    Science.gov (United States)

    Xue, Yu; Xie, Juanjuan; Fang, Pan; Yao, Jun; Yan, Guoquan; Shen, Huali; Yang, Pengyuan

    2018-04-16

    Glycosylation is a crucial process in protein biosynthesis. However, the analysis of glycopeptides through MS remains challenging due to the microheterogeneity and macroheterogeneity of the glycoprotein. Selective enrichment of glycopeptides from complex samples prior to MS analysis is essential for successful glycoproteome research. In this work, we systematically investigated the behaviors and performances of boronic acid chemistry, ZIC-HILIC, and PGC of glycopeptide enrichment to promote understanding of these methods. We also optimized boronic acid chemistry and ZIC-HILIC enrichment methods and applied them to enrich glycopeptides from mouse liver. The intact N-glycopeptides were interpreted using the in-house analysis software pGlyco 2.0. We found that boronic acid chemistry in this study preferred to capture glycopeptides with high mannose glycans, ZIC-HILIC enriched most N-glycopeptides and did not show significant preference during enrichment and PGC was not suitable for separating glycopeptides with a long amino acid sequence. We performed a detailed study on the behaviors and performances of boronic acid chemistry, ZIC-HILIC, and PGC enrichment methods and provide a better understanding of enrichment methods for further glycoproteomics research.

  20. Direct chemoselective synthesis of glyconanoparticles from unprotected reducing glycans and glycopeptide aldehydes

    DEFF Research Database (Denmark)

    Thygesen, Mikkel Boas; Sørensen, Kasper Kildegaard; Cló, Emiliano

    2009-01-01

    Chemoselective oxime coupling was used for facile conjugation of unprotected, reducing glycans and glycopeptide aldehydes with core-shell gold nanoparticles carrying reactive aminooxy groups on the organic shell.......Chemoselective oxime coupling was used for facile conjugation of unprotected, reducing glycans and glycopeptide aldehydes with core-shell gold nanoparticles carrying reactive aminooxy groups on the organic shell....

  1. Characterization of an immunodominant cancer-specific O-glycopeptide epitope in murine podoplanin (OTS8)

    DEFF Research Database (Denmark)

    Steentoft, Catharina; Schjoldager, Katrine T; Cló, Emiliano

    2010-01-01

    antibody 237, developed to a spontaneous murine fibrosarcoma, was shown to be directed to murine podoplanin (OTS8) with truncated Tn O-glycans. Our understanding of such cancer-specific auto-antibodies to truncated glycoforms of glycoproteins is limited. Here we have investigated immunogenicity...... of a chemoenzymatically produced Tn-glycopeptide derived from the putative murine podoplanin O-glycopeptide epitope. We found that the Tn O-glycopeptide was highly immunogenic in mice and produced a Tn-glycoform specific response with no reactivity against unglycosylated peptides or the O-glycopeptide with extended O......-glycan (STn and T glycoforms). The immunodominant epitope was strictly dependent on the peptide sequence, required Tn at a specific single Thr residue (Thr(77)), and antibodies to the epitope were not found in naive mice. We further tested a Tn O-glycopeptide library derived from human podoplanin...

  2. Differential Isotope Labeling of Glycopeptides for Accurate Determination of Differences in Site-Specific Glycosylation.

    Science.gov (United States)

    Pabst, Martin; Benešová, Iva; Fagerer, Stephan R; Jacobsen, Mathias; Eyer, Klaus; Schmidt, Gregor; Steinhoff, Robert; Krismer, Jasmin; Wahl, Fabian; Preisler, Jan; Zenobi, Renato

    2016-01-04

    We introduce a stable isotope labeling approach for glycopeptides that allows a specific glycosylation site in a protein to be quantitatively evaluated using mass spectrometry. Succinic anhydride is used to specifically label primary amino groups of the peptide portion of the glycopeptides. The heavy form (D4(13)C4) provides an 8 Da mass increment over the light natural form (H4(12)C4), allowing simultaneous analysis and direct comparison of two glycopeptide profiles in a single MS scan. We have optimized a protocol for an in-solution trypsin digestion, a one-pot labeling procedure, and a post-labeling solid-phase extraction to obtain purified and labeled glycopeptides. We provide the first demonstration of this approach by comparing IgG1 Fc glycopeptides from polyclonal IgG samples with respect to their galactosylation and sialylation patterns using MALDI MS and LC-ESI-MS.

  3. Cancer biomarkers defined by autoantibody signatures to aberrant O-glycopeptide epitopes

    DEFF Research Database (Denmark)

    Wandall, Hans H; Blixt, Ola; Tarp, Mads A

    2010-01-01

    Autoantibodies to cancer antigens hold promise as biomarkers for early detection of cancer. Proteins that are aberrantly processed in cancer cells are likely to present autoantibody targets. The extracellular mucin MUC1 is overexpressed and aberrantly glycosylated in many cancers; thus, we evalua...

  4. Complex Regulatory Networks Governing Production of the Glycopeptide A40926

    Directory of Open Access Journals (Sweden)

    Rosa Alduina

    2018-04-01

    Full Text Available Glycopeptides (GPAs are an important class of antibiotics, with vancomycin and teicoplanin being used in the last 40 years as drugs of last resort to treat infections caused by Gram-positive pathogens, including methicillin-resistant Staphylococcus aureus. A few new GPAs have since reached the market. One of them is dalbavancin, a derivative of A40926 produced by the actinomycete Nonomuraea sp. ATCC 39727, recently classified as N. gerenzanensis. This review summarizes what we currently know on the multilevel regulatory processes governing production of the glycopeptide A40926 and the different approaches used to increase antibiotic yields. Some nutrients, e.g., valine, l-glutamine and maltodextrin, and some endogenous proteins, e.g., Dbv3, Dbv4 and RpoBR, have a positive role on A40926 biosynthesis, while other factors, e.g., phosphate, ammonium and Dbv23, have a negative effect. Overall, the results available so far point to a complex regulatory network controlling A40926 in the native producing strain.

  5. Complex Regulatory Networks Governing Production of the Glycopeptide A40926.

    Science.gov (United States)

    Alduina, Rosa; Sosio, Margherita; Donadio, Stefano

    2018-04-05

    Glycopeptides (GPAs) are an important class of antibiotics, with vancomycin and teicoplanin being used in the last 40 years as drugs of last resort to treat infections caused by Gram-positive pathogens, including methicillin-resistant Staphylococcus aureus . A few new GPAs have since reached the market. One of them is dalbavancin, a derivative of A40926 produced by the actinomycete Nonomuraea sp. ATCC 39727, recently classified as N. gerenzanensis . This review summarizes what we currently know on the multilevel regulatory processes governing production of the glycopeptide A40926 and the different approaches used to increase antibiotic yields. Some nutrients, e.g., valine, l-glutamine and maltodextrin, and some endogenous proteins, e.g., Dbv3, Dbv4 and RpoB R , have a positive role on A40926 biosynthesis, while other factors, e.g., phosphate, ammonium and Dbv23, have a negative effect. Overall, the results available so far point to a complex regulatory network controlling A40926 in the native producing strain.

  6. Presence of fucosyl residues on the oligosaccharide antennae of membrane glycopeptides of human neuroblastoma cells

    International Nuclear Information System (INIS)

    Santer, U.V.; Glick, M.C.

    1983-01-01

    Fucosyl residues linked alpha 1 leads to 3 or 4 to N-acetylglucosamine were found in large amounts on glycopeptides from the membranes of human tumor cells of neurectodermal origin but not on membrane glycopeptides from human fibroblasts. The fucosyl residues were detected by release of radioactive fucose from the glycopeptides with an almond alpha-L-fucosidase specific for fucosyl alpha 1 leads to 3(4)-N-acetylglucosamine. In other studies, the linkage was shown to be alpha 1 leads to 3 by nuclear magnetic resonance analysis. Glycopeptides containing these fucosyl residues from four human neuroblastoma cell lines were defined by binding to immobilized lectins. In addition, the glycopeptides from one human neuroblastoma cell line, CHP-134, were further characterized by enzyme degradation and columns calibrated for size and charge. The antennary position of fucosyl alpha 1 leads to 3-N-acetylglucosamine on the glycopeptides was demonstrated by the use of exoglycosidases and endoglycosidase D, since complete degradation to yield fucosyl-N-acetylglucosaminylasparagine was obtained only after treatment with almond alpha-L-fucosidase prior to the sequential degradation. Fucosyl alpha 1 leads to 3-N-acetylglucosamine was present on most size and charge classes of membrane glycopeptides and therefore was not limited to a few glycoproteins. Since the almond alpha-L-fucosidase cleaves fucosyl residues from glycoproteins, the physiological effects of the increased specific fucosylation on human tumors of neurectodermal origin can be examined

  7. Highly Selective Enrichment of Glycopeptides Based on Zwitterionically Functionalized Soluble Nanopolymers

    Science.gov (United States)

    Cao, Weiqian; Huang, Jiangming; Jiang, Biyun; Gao, Xing; Yang, Pengyuan

    2016-07-01

    Efficient glycopeptides enrichment prior to mass spectrometry analysis is essential for glycoproteome study. ZIC-HILIC (zwitterionic hydrophilic interaction liquid chromatography) based glycopeptides enrichment approaches have been attracting more attention for several benefits like easy operating, high enrichment specificity and intact glycopeptide retained. In this study, Poly (amidoamine) dendrimer (PAMAM) was adopted for the synthesis of zwitterionically functionalized (ZICF) materials for glycopeptide enrichment. The multiple branched structure and good solubility of ZICF-PAMAM enables a sufficient interaction with glycopeptides. The ZICF-PAMAM combined with the FASP-mode enrichment strategy exhibits more superior performance compared with the existing methods. It has the minimum detectable concentration of femtomolar level and high recovery rate of over 90.01%, and can efficiently enrich glycopeptides from complex biological samples even for merely 0.1 μL human serum. The remarkable glycopeptides enrichment capacity of ZICF-PAMAM highlights the potential application in in-depth glycoproteome research, which may open up new opportunities for the development of glycoproteomics.

  8. Synthesis, Properties, and Mechanism of Action of New Generation of Polycyclic Glycopeptide Antibiotics.

    Science.gov (United States)

    Olsufyeva, Eugenia N; Tevyashova, Anna N

    2017-01-01

    The increased resistance of glycopeptide based antibiotics has become a serious problem for the chemotherapy of infections triggered by resistant Gram-positive bacteria. This has motivated the urgent sincere efforts to develop potent glycopeptide-based antibiotics in both academy and industry research laboratories. Understanding of the mechanism of action of natural and modified glycopeptides is considered as the basis for the rational design of compounds with valuable properties to achieve the fundamental results. Several hydrophobic glycopeptide analogues active against resistant strains were developed during the last two decades. Three drugs, namely, oritavancin, telavancin and dalbavancin were approved by FDA in 2013-2014. It was found that hydrophobic derivatives act through different mechanisms without binding with the modified target of resistant bacteria. Types: Different types of chemical modifications led to several glycopeptide analogues active against Gram-negative bacteria as advocated by in vitro studies or demonstrating potent antiviral activity in the cell models. A new class of glycopeptide antibiotics with potent activity against sensitive and resistant bacterial strains has been recently reported with the aim to overcome the resistance, however, there are a lot of obscure problems in the complete understanding of their mechanisms of actions. In this review, we summarized the achievements of synthetic methods devoted to the construction of new polycyclic glycopeptide antibiotics and described the studies related to their mechanism of actions. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  9. Inflammatory Modulation Effect of Glycopeptide from Ganoderma capense (Lloyd Teng

    Directory of Open Access Journals (Sweden)

    Yan Zhou

    2014-01-01

    Full Text Available Glycopeptide from Ganoderma capense (Lloyd Teng (GCGP injection is widely used in kinds of immune disorders, but little is known about the molecular mechanisms of how GCGP could interfere with immune cell function. In the present study, we have found that GCGP had inflammatory modulation effects on macrophage cells to maintain NO production and iNOS expression at the normal level. Furthermore, western blot analysis showed that the underlying mechanism of immunomodulatory effect of GCGP involved NF-κB p65 translation, IκB phosphorylation, and degradation; NF-κB inhibitor assays also confirmed the results. In addition, competition study showed that GCGP could inhibit LPS from binding to macrophage cells. Our data indicates that GCGP, which may share the same receptor(s expressed by macrophage cells with LPS, exerted immunomodulatory effect in a NF-κB-dependent signaling pathway in macrophages.

  10. Inflammatory Modulation Effect of Glycopeptide from Ganoderma capense (Lloyd) Teng

    Science.gov (United States)

    Zhou, Yan; Chen, Song; Yao, Wenbing; Gao, Xiangdong

    2014-01-01

    Glycopeptide from Ganoderma capense (Lloyd) Teng (GCGP) injection is widely used in kinds of immune disorders, but little is known about the molecular mechanisms of how GCGP could interfere with immune cell function. In the present study, we have found that GCGP had inflammatory modulation effects on macrophage cells to maintain NO production and iNOS expression at the normal level. Furthermore, western blot analysis showed that the underlying mechanism of immunomodulatory effect of GCGP involved NF-κB p65 translation, IκB phosphorylation, and degradation; NF-κB inhibitor assays also confirmed the results. In addition, competition study showed that GCGP could inhibit LPS from binding to macrophage cells. Our data indicates that GCGP, which may share the same receptor(s) expressed by macrophage cells with LPS, exerted immunomodulatory effect in a NF-κB-dependent signaling pathway in macrophages. PMID:24966469

  11. Hexose rearrangements upon fragmentation of N-glycopeptides and reductively aminated N-glycans.

    Science.gov (United States)

    Wuhrer, Manfred; Koeleman, Carolien A M; Deelder, André M

    2009-06-01

    Tandem mass spectrometry of glycans and glycoconjugates in protonated form is known to result in rearrangement reactions leading to internal residue loss. Here we studied the occurrence of hexose rearrangements in tandem mass spectrometry of N-glycopeptides and reductively aminated N-glycans by MALDI-TOF/TOF-MS/MS and ESI-ion trap-MS/MS. Fragmentation of proton adducts of oligomannosidic N-glycans of ribonuclease B that were labeled with 2-aminobenzamide and 2-aminobenzoic acid resulted in transfer of one to five hexose residues to the fluorescently tagged innermost N-acetylglucosamine. Glycopeptides from various biological sources with oligomannosidic glycans were likewise shown to undergo hexose rearrangement reactions, resulting in chitobiose cleavage products that have acquired one or two hexose moieties. Tryptic immunoglobulin G Fc-glycopeptides with biantennary N-glycans likewise showed hexose rearrangements resulting in hexose transfer to the peptide moiety retaining the innermost N-acetylglucosamine. Thus, as a general phenomenon, tandem mass spectrometry of reductively aminated glycans as well as glycopeptides may result in hexose rearrangements. This characteristic of glycopeptide MS/MS has to be considered when developing tools for de novo glycopeptide structural analysis.

  12. Expressão de CDX2 e mucinas (MUC1, MUC2, MUC5AC e MUC6 em esôfago de Barrett antes e após fundoplicatura de Nissen Expression of CDX2 and mucins (MUC1, MUC2, MUC5AC and MUC6 in Barrett's esophagus before and after Nissen fundoplication

    Directory of Open Access Journals (Sweden)

    Luciana Rodrigues de Meirelles

    2012-10-01

    Full Text Available INTRODUÇÃO: O esôfago de Barrett (EB corresponde à substituição do epitélio escamoso por um do tipo intestinal, em resposta ao refluxo crônico nos pacientes com doença do refluxo gastroesofágico (DRGE. É um importante precursor do adenocarcinoma esofágico. A fundoplicatura de Nissen (FN é uma cirurgia antirrefluxo que visa a reduzir a agressão à mucosa esofágica. Alterações no padrão de expressão imuno-histoquímica de mucinas e de CDX2 no EB antes e depois da FN podem ser úteis na identificação de um padrão de expressão desses marcadores e, eventualmente, na identificação de casos com risco de evolução para malignidade. OBJETIVOS: Avaliar e comparar a imunoexpressão de CDX2 e mucinas no EB de pacientes com DRGE submetidos à FN antes e após a cirurgia. MATERIAIS E MÉTODOS: Estudo retrospectivo de 25 pacientes com diagnóstico de DRGE e EB submetidos à FN, acompanhados por, pelo menos, três anos. Foram feitos análise histológica e estudo imuno-histoquímico das biópsias endoscópicas antes e após a cirurgia, comparando-se a inflamação e a imunoexpressão de MUC1, MUC2, MUC5AC, MUC6 e CDX2. Estimou-se a porcentagem de células com expressão para os marcadores estudados na mucosa de Barrett: 0%-25%, 25%-75% e 75%-100% das células positivas. Foram utilizados os testes de McNemar e Stuart-William e adotou-se o nível de 5% de significância estatística. RESULTADOS E CONCLUSÃO: Não houve diferenças significativas quanto a presença ou intensidade de inflamação, nem da imunoexpressão de mucinas e CDX2 no EB antes e após a FN. O tratamento cirúrgico não influenciou a mudança da expressão dessas glicoproteínas no EB.INTRODUCTION: Barrett´s esophagus (BE is characterized by the exchange of esophageal squamous epithelium for intestinal type in response to chronic reflux in patients with gastroesophageal reflux disease (GERD.It is an important precursor of esophageal adenocarcinoma. Nissen

  13. Selective enrichment of sialic acid-containing glycopeptides using titanium dioxide chromatography with analysis by HILIC and mass spectrometry

    DEFF Research Database (Denmark)

    Palmisano, Giuseppe; Lendal, Sara Eun; Engholm-Keller, Kasper

    2010-01-01

    -containing glycopeptides is achieved by using a low-pH buffer that contains a substituted acid such as glycolic acid to improve the binding efficiency and selectivity of SA-containing glycopeptides to the TiO(2) resin. By combining TiO(2) enrichment of sialylated glycopeptides with HILIC separation of deglycosylated...... of glycosylation sites and the characterization of glycan structures. In this paper, we describe a protocol for the selective enrichment of SA-containing glycopeptides using a combination of titanium dioxide (TiO(2)) and hydrophilic interaction liquid chromatography (HILIC). The selectivity of TiO(2) toward SA...... peptides, a more comprehensive analysis of formerly sialylated glycopeptides by MS can be achieved. Here we illustrate the efficiency of the method by the identification of 1,632 unique formerly sialylated glycopeptides from 817 sialylated glycoproteins. The TiO(2)/HILIC protocol requires 2 d...

  14. Self-Adjuvanting Glycopeptide Conjugate Vaccine against Disseminated Candidiasis

    Science.gov (United States)

    Xin, Hong; Cartmell, Jonathan; Bailey, Justin J.; Dziadek, Sebastian; Bundle, David R.; Cutler, Jim E.

    2012-01-01

    Our research on pathogenesis of disseminated candidiasis led to the discovery that antibodies specific for Candida albicans cell surface β-1, 2–mannotriose [β-(Man)3] protect mice. A 14 mer peptide Fba, which derived from the N-terminal portion of the C. albicans cytosolic/cell surface protein fructose-bisphosphate aldolase, was used as the glycan carrier and resulted in a novel synthetic glycopeptide vaccine β-(Man)3-Fba. By a dendritic cell-based immunization approach, this conjugate induced protective antibody responses against both the glycan and peptide parts of the vaccine. In this report, we modified the β-(Man)3-Fba conjugate by coupling it to tetanus toxoid (TT) in order to improve immunogenicity and allow for use of an adjuvant suitable for human use. By new immunization procedures entirely compatible with human use, the modified β-(Man)3-Fba-TT was administered either alone or as a mixture made with alum or monophosphoryl lipid A (MPL) adjuvants and given to mice by a subcutaneous (s.c.) route. Mice vaccinated with or, surprisingly, without adjuvant responded well by making robust antibody responses. The immunized groups showed a high degree of protection against a lethal challenge with C. albicans as evidenced by increased survival times and reduced kidney fungal burden as compared to control groups that received only adjuvant or DPBS buffer prior to challenge. To confirm that induced antibodies were protective, sera from mice immunized against the β-(Man)3-Fba-TT conjugate transferred protection against disseminated candidiasis to naïve mice, whereas C. albicans-absorbed immune sera did not. Similar antibody responses and protection induced by the β-(Man)3-Fba-TT vaccine was observed in inbred BALB/c and outbred Swiss Webster mice. We conclude that addition of TT to the glycopeptide conjugate results in a self-adjuvanting vaccine that promotes robust antibody responses without the need for additional adjuvant, which is novel and represents a

  15. Liposomal preparations of muramyl glycopeptides as immunomodulators and adjuvants.

    Science.gov (United States)

    Turánek, Jaroslav; Ledvina, Miroslav; Kasná, Andrea; Vacek, Antonín; Hríbalova, Vera; Krejcí, Josef; Miller, Andrew D

    2006-04-12

    The need for safe and structurally defined immunomodulators and adjuvants is increasing in connection with the recently observed marked increase in the prevalence of pathological conditions characterized by immunodeficiency. Important groups of such compounds are muramyl glycopeptides, analogs of muramyl dipeptide (MDP), glucosaminyl-muramyl dipeptide (GMDP), and desmuramylpeptides. We have designed and synthesized new types of analogs with changes in both the sugar and the peptide parts of the molecule that show a high immunostimulating and adjuvant activity and suppressed adverse side effects. The introduction of lipophilic residues has also improved their incorporation into liposomes, which represent a suitable drug carrier. The proliposome-liposome method is based on the conversion of the initial proliposome preparation into liposome dispersion by dilution with the aqueous phase. The description of a home-made stirred thermostated cell and its link-up with a liquid delivery system for a rapid and automated preparation of multilamellar liposomes at strictly controlled conditions (sterility, temperature, dilution rate and schedule) is presented. The cell has been designed for laboratory-scale preparation of liposomes (300-1000 mg of phospholipid per run) in a procedure taking less than 90 min. The method can be readily scaled up. Examples of adjuvant and immunostimulatory effect of liposomal preparation in mice model will be presented.

  16. Glycopeptide resistance in Enterococcus faecium from broilers and pigs following discontinued use of avoparcin

    DEFF Research Database (Denmark)

    Bager, Flemming; Aarestrup, Frank Møller; Madsen, Mogens

    1999-01-01

    The use of the glycopeptide growth promoter avoparcin was discontinued in Denmark in 1995 following concerns that vancomycin-resistant Enterococcus faecium occurring as a result of its use could be transferred to humans via food. The present study is an analysis of results obtained by the continu......The use of the glycopeptide growth promoter avoparcin was discontinued in Denmark in 1995 following concerns that vancomycin-resistant Enterococcus faecium occurring as a result of its use could be transferred to humans via food. The present study is an analysis of results obtained...... by the continuous surveillance of an antimicrobial resistance in Denmark (DANMAP) with the aim of determining the effect of the ban on the occurrence of glycopeptide resistance among E, faecium isolated from broilers and pigs, Among isolates from broilers, the proportion that were resistant to glycopeptides has....... Alternatively, the results indicate that the different outcomes may result from different co-selection patterns in pigs and broilers. In pigs, the antimicrobials most commonly used favored co-selection of glycopeptide-resistant strains of E. faecium while in broilers the antimicrobials most widely used selected...

  17. Relationship between copper, glycopeptide, and macrolide resistance among Enterococcus faecium strains isolated from pigs in Denmark between 1997 and 2003

    DEFF Research Database (Denmark)

    Hasman, Henrik; Aarestrup, Frank Møller

    2005-01-01

    A significant relationship between copper resistance (tcrB), glycopeptide resistance (Tn1546), and macrolide resistance [erm(B)] in Enterococcus faecium isolated from pigs was found. The tcrB gene was located closely upstream of the Tn1546 element. However, the continued use of copper sulfate has...... not been able to maintain high levels of macrolide and glycopeptide resistance....

  18. Belief Elicitation in Experiments

    DEFF Research Database (Denmark)

    Blanco, Mariana; Engelmann, Dirk; Koch, Alexander

    Belief elicitation in economics experiments usually relies on paying subjects according to the accuracy of stated beliefs in addition to payments for other decisions. Such incentives, however, allow risk-averse subjects to hedge with their stated beliefs against adverse outcomes of other decisions......-belief elicitation treatment using a financial investment frame, where hedging arguably would be most natural....

  19. Synthesis of Cyclic Antifreeze Glycopeptide and Glycopeptoids and Their Ice Recrystallization Inhibition Activity

    International Nuclear Information System (INIS)

    Ahn, Mija; Murugan, Ravichandran N.; Bang, Jeong Kyu; Kim, Hak Jun; Shin, Song Yub; Kim, Eunjung; Lee, Jun Hyuck

    2012-01-01

    Until now, few groups reported the antifreeze activity of cyclic glycopeptides; however, the tedious synthetic procedure is not amenable to study the intensive structure activity relationship. A series of N-linked cyclic glycopeptoids and glycopeptide have been prepared to evaluate antifreeze activity as a function of peptide backbone cyclization and methyl stereochemical effect on the rigid Thr position. This study has combined the cyclization protocol with solid phase peptide synthesis and obtained significant quantities of homogeneous cyclic glycopeptide and glycopeptoids. Analysis of antifreeze activity revealed that our cyclic peptide demonstrated RI activity while cyclic glycopeptoids showed no RI activity. These results suggest that the subtle changes in conformation and Thr orientation dramatically influence RI activity of N-linked glycopeptoids

  20. [Emergence of glycopeptide resistant Enterococcus faecium in Algeria: a case report].

    Science.gov (United States)

    Hamidi, Moufida; Ammari, Houria; Ghaffor, Mohamed; Benamrouche, Nabila; Tali-Maamar, Hassiba; Tala-Khir, Farida; Younsi, Mokhtar; Rahal, Kheira

    2013-01-01

    A glycopeptide-resistant Enterococcus faecium (EFRG) was isolated from a wound in a patient hospitalized in a university hospital in Algiers. This strain was resistant to several antibiotics. This patient was carrying this strain in the digestive tract which may partly explain its origin. Genotypic comparison of the two strains by pulsed field gel electrophoresis showed that it was the same strain. Glycopeptide resistance was due to the presence of the vanA gene. Vigilance is required facing the emergence of strains of EFRG in our hospitals.

  1. Substrate uptake, phosphorus repression, and effect of seed culture on glycopeptide antibiotic production

    DEFF Research Database (Denmark)

    Maiti, Soumen K.; Singh, Kamaleshwar P.; Eliasson Lantz, Anna

    2010-01-01

    may experience catabolite repression by one or more of the substrates. Availability of reliable process models is a key bottleneck in optimization of such processes. Here we present a structured kinetic model to describe the growth, substrate uptake and product formation for the glycopeptide....... The model is also able to predict key phenomena such as simultaneous uptake of glucose and glycerol but with different specific uptake rates, and inhibition of glycopeptide production by high intracellular phosphate levels. The model is successfully applied to both production and seed medium with varying....... The model may have applications in optimizing seed transfer, medium composition, and feeding strategy for maximizing production....

  2. Synthetic biocompatible polymers are an effective delivery platform that elicits potent antibody responses against HIV-1 glycopeptide immunogens

    Czech Academy of Sciences Publication Activity Database

    Francica, J.; Lynn, G.; Laga, Richard; Aussedat, B.; Meyerhoff, R.; Alam, M.; Danishefsky, S.; Haynes, B.; Seder, R.

    2016-01-01

    Roč. 32, Supplement 1 (2016), s. 221-P07.27 ISSN 0889-2229. [Conference on HIV Research for Prevention - HIV R4P. 17.10.2016-21.10.2016, Chicago] Institutional support: RVO:61389013 Keywords : biocompatible polymers * druh delivery Subject RIV: CD - Macromolecular Chemistry

  3. Development of a data independent acquisition mass spectrometry workflow to enable glycopeptide analysis without predefined glycan compositional knowledge.

    Science.gov (United States)

    Lin, Chi-Hung; Krisp, Christoph; Packer, Nicolle H; Molloy, Mark P

    2018-02-10

    Glycoproteomics investigates glycan moieties in a site specific manner to reveal the functional roles of protein glycosylation. Identification of glycopeptides from data-dependent acquisition (DDA) relies on high quality MS/MS spectra of glycopeptide precursors and often requires manual validation to ensure confident assignments. In this study, we investigated pseudo-MRM (MRM-HR) and data-independent acquisition (DIA) as alternative acquisition strategies for glycopeptide analysis. These approaches allow data acquisition over the full MS/MS scan range allowing data re-analysis post-acquisition, without data re-acquisition. The advantage of MRM-HR over DDA for N-glycopeptide detection was demonstrated from targeted analysis of bovine fetuin where all three N-glycosylation sites were detected, which was not the case with DDA. To overcome the duty cycle limitation of MRM-HR acquisition needed for analysis of complex samples such as plasma we trialed DIA. This allowed development of a targeted DIA method to identify N-glycopeptides without pre-defined knowledge of the glycan composition, thus providing the potential to identify N-glycopeptides with unexpected structures. This workflow was demonstrated by detection of 59 N-glycosylation sites from 41 glycoproteins from a HILIC enriched human plasma tryptic digest. 21 glycoforms of IgG1 glycopeptides were identified including two truncated structures that are rarely reported. We developed a data-independent mass spectrometry workflow to identify specific glycopeptides from complex biological mixtures. The novelty is that this approach does not require glycan composition to be pre-defined, thereby allowing glycopeptides carrying unexpected glycans to be identified. This is demonstrated through the analysis of immunoglobulins in human plasma where we detected two IgG1 glycoforms that are rarely observed. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Two-Dimensional MoS2-Based Zwitterionic Hydrophilic Interaction Liquid Chromatography Material for the Specific Enrichment of Glycopeptides.

    Science.gov (United States)

    Xia, Chaoshuang; Jiao, Fenglong; Gao, Fangyuan; Wang, Heping; Lv, Yayao; Shen, Yehua; Zhang, Yangjun; Qian, Xiaohong

    2018-06-05

    Mass spectrometry (MS)-based glycoproteomics research requires highly efficient sample preparation to eliminate interference from non-glycopeptides and to improve the efficiency of glycopeptide detection. In this work, a novel MoS 2 /Au-NP (gold nanoparticle)-L-cysteine nanocomposite was prepared for glycopeptide enrichment. The two-dimensional (2D) structured MoS 2 nanosheets served as a matrix that could provide a large surface area for immobilizing hydrophilic groups (such as L-cysteine) with low steric hindrance between the materials and the glycopeptides. As a result, the novel nanomaterial possessed an excellent ability to capture glycopeptides. Compared to commercial zwitterionic hydrophilic interaction liquid chromatography (ZIC-HILIC) materials, the novel nanomaterials exhibited excellent enrichment performance with ultrahigh selectivity and sensitivity (approximately 10 fmol), high binding capacity (120 mg g -1 ), high enrichment recovery (more than 93%), satisfying batch-to-batch reproducibility, and good universality for glycopeptide enrichment. In addition, its outstanding specificity and efficiency for glycopeptide enrichment was confirmed by the detection of glycopeptides from an human serum immunoglobulin G (IgG) tryptic digest in quantities as low as a 1:1250 molar ratio of IgG tryptic digest to bovine serum albumin tryptic digest. The novel nanocomposites were further used for the analysis of complex samples, and 1920 glycopeptide backbones from 775 glycoproteins were identified in three replicate analyses of 50 μg of proteins extracted from HeLa cell exosomes. The resulting highly informative mass spectra indicated that this multifunctional nanomaterial-based enrichment method could be used as a promising tool for the in-depth and comprehensive characterization of glycoproteomes in MS-based glycoproteomics.

  5. Correlation between Sweet Spots of Glycopeptides and Polymorphism of the Matrix Crystal in MALDI Samples.

    Science.gov (United States)

    Nishikaze, Takashi; Okumura, Hisako; Jinmei, Hiroshi; Amano, Junko

    2012-01-01

    A standard dried-droplet preparation using 2,5-dihydroxybenzoic acid (2,5-DHBA) as the matrix results in a large variation in signal intensity and poor shot-to-shot reproducibility in matrix-assisted laser desorption/ionization (MALDI). We expected that the differences can be attributed to the nature of the crystal structures in the region of the "sweet spot" within the MALDI samples. 2,5-DHBA crystals with and without analytes on a target plate obtained by means of a dried-droplet preparation contain two polymorphs, which can be distinguished by Raman spectra. In comparing the Raman image with the MS image, a clear correlation between the signal distribution of glycopeptides and hydrophilic peptides and the specific crystal form of 2,5-DHBA could be made. The ionization of hydrophobic peptides appears to proceed in both types of polymorphic crystals. In addition, the derivatization of glycopeptides with a pyrene group enabled us to detect glycopeptides regardless the crystal form. As the result, the number of sweet spots increased and MS spectra with a high signal intensity were obtained. The results suggest that the introduction of a hydrophobic/aromatic moiety to glycopeptides results in a more successful MALDI analysis due to the effective incorporation of the analyte into matrix crystals.

  6. Development of infection with Streptococcus bovis and Aspergillus sp. in irradiated mice after glycopeptide therapy

    International Nuclear Information System (INIS)

    Brook, I.; Tom, S.P.; Ledney, G.D.

    1993-01-01

    The use of ofloxacin and glycopeptides was evaluated for the treatment of infections arising in C3H/HeN female mice irradiated with 8.3 Gy from a 60 Co source. The 21 day regimen began 72 h after irradiation when each of five sets of experimental animals received three antimicrobial therapy regimens and a saline-treated control group. With 40 mice in each group, 20 were used to monitor survival, 20 for the recovery of bacteria from the liver culture. Treatment groups were oral ofloxacin; oral or intramuscular vancomycin oral teicoplanin, ofloxacin and vancomycin; ofloxacin and teicoplanin; or saline. Bacteria recovered from saline treated mice were Enterobacteriaceae and Streptococcus spp. By comparison, fewer Enterobacteriaceae were isolated from ofloxacin treated mice and fewer Streptococcus spp. in both vancomycin and teicoplanin treated mice. However, glycopeptide-treated mice developed infection with Aspergillis fumigatus and glycopeptide resistant Streptococcus bovis. Mortality rates within 60 days of irradiation were 100% in all treatment and control groups with the exception of ofloxacin which was 25%-35%. These data suggest that glycopeptide therapy increases rates of systemic infection with fungi and antibiotic resistant bacteria in irradiated mice. (Author)

  7. Carbohydrates of influenza virus. I. Glycopeptides derived from viral glycoproteins after labeling with radioactive sugars

    International Nuclear Information System (INIS)

    Schwarz, R.T.; Schmidt, M.F.G.; Anwer, U.; Klenk, H.D.

    1977-01-01

    The carbohydrate moiety of the influenza glycoproteins NA, HA 1 , and HA 2 were analyzed by labeling with radioactive sugars. Analysis of glycopeptides obtained after digestion with Pronase indicated that there are at least two different types of carbohydrate side chains. The side chain of type I is composed of glucosamine, mannose, galactose, and fucose. It is found on NA, HA 1 , and HA 2 . The side chain of type II contains a high amount of mannose and is found only on NA and HA 2 . The molecular weights of the corresponding glycopeptides obtained from virus grown in chicken ambryo cells are 2,600 for type I and 2,000 for type II. The glycoproteins of virus grown in MDBK cells have a higher molecular weight than those of virus grown in chicken embryo cells, and there is a corresponding difference in the molecular weights of the glycopeptides. Under conditions of partial inhibition of glycosylation, virus particles were isolated that contained hemagglutinin with reduced carbohydrate content. Glycopeptide analysis indicated that this reduction is due to the lack of whole carbohydrate side chains and not to the incorporation of incomplete ones. This observation suggests that glycosylation of the viral glycoproteins involves en bloc transfer of the core sugars to the polypeptide chains

  8. Development of infection with Streptococcus bovis and Aspergillus sp. in irradiated mice after glycopeptide therapy

    Energy Technology Data Exchange (ETDEWEB)

    Brook, I.; Tom, S.P.; Ledney, G.D. (Armed Forces Radiobiology Research Inst., Bethesda, MD (United States))

    1993-11-01

    The use of ofloxacin and glycopeptides was evaluated for the treatment of infections arising in C3H/HeN female mice irradiated with 8.3 Gy from a [sup 60]Co source. The 21 day regimen began 72 h after irradiation when each of five sets of experimental animals received three antimicrobial therapy regimens and a saline-treated control group. With 40 mice in each group, 20 were used to monitor survival, 20 for the recovery of bacteria from the liver culture. Treatment groups were oral ofloxacin; oral or intramuscular vancomycin oral teicoplanin, ofloxacin and vancomycin; ofloxacin and teicoplanin; or saline. Bacteria recovered from saline treated mice were Enterobacteriaceae and Streptococcus spp. By comparison, fewer Enterobacteriaceae were isolated from ofloxacin treated mice and fewer Streptococcus spp. in both vancomycin and teicoplanin treated mice. However, glycopeptide-treated mice developed infection with Aspergillis fumigatus and glycopeptide resistant Streptococcus bovis. Mortality rates within 60 days of irradiation were 100% in all treatment and control groups with the exception of ofloxacin which was 25%-35%. These data suggest that glycopeptide therapy increases rates of systemic infection with fungi and antibiotic resistant bacteria in irradiated mice. (Author).

  9. Molecular Characterization of Glycopeptide-Resistant Enterococci from Hospitals of the Picardy Region (France

    Directory of Open Access Journals (Sweden)

    M. Biendo

    2010-01-01

    Full Text Available We studied 138 glycopeptide-resistant enterococci (GRE strains, consisting of 131 glycopeptide-resistant Enterococcus faecium (GREfm and 7 glycopeptide-resistant Enterococcus faecalis (GREfs. The GREfm strains were resistant to penicillin, ampicillin, vancomycin, and teicoplanin, while the GREfs strains were only resistant to vancomycin and teicoplanin. The van A gene was the only glycopeptide determinant present in all GRE isolates investigated. Genes coding for Hyl and Hyl+ Esp were detected in 39 (29.8% and 92 (70.2% of the 131 GREfm isolates, respectively. Three of the 7 GREfs were positive for gelE+asa 1 genes, 3 for gel E gene, and 1 for asa 1 gene. The genetic relationship between the 138 GRE was analyzed by pulsed-field gel electrophoresis (PFGE and multilocus sequence typing (MLST. GREfm isolates were clustered in a single genogroup (pulsotype A, and GREfs were clustered in six genogroups (pulsotypes B-G. Among the isolates investigated by MLST, only 18 PCR products were sequenced (12 E. faecium and 6 E. faecalis, and 9 sequence types (STs were identified.

  10. Biosynthetic studies of the glycopeptide teicoplanin by 1H and 13C NMR

    DEFF Research Database (Denmark)

    Heydorn, Arne; Petersen, Bent O.; Duus, Jens Øllgaard

    2000-01-01

    The biosynthesis of the glycopeptide antibiotic teicoplanin was studied by growing a teicoplanin producing strain of Actinoplanes teichomyceticus (ATCC 31121) on glucose containing either 34.0% [1-13C]glucose or 9.7% [U- 13C]glucose. The fractional enrichment pattern of teicoplanin produced in th...

  11. Boronic Acid functionalized core-shell polymer nanoparticles prepared by distillation precipitation polymerization for glycopeptide enrichment.

    Science.gov (United States)

    Qu, Yanyan; Liu, Jianxi; Yang, Kaiguang; Liang, Zhen; Zhang, Lihua; Zhang, Yukui

    2012-07-16

    The boronic acid-functionalized core-shell polymer nanoparticles, poly(N,N-methylenebisacrylamide-co-methacrylic acid)@4-vinylphenylboronic acid (poly(MBA-co-MAA)@VPBA), were successfully synthesized for enriching glycosylated peptides. Such nanoparticles were composed of a hydrophilic polymer core prepared by distillation precipitation polymerization (DPP) and a boronic acid-functionalized shell designed for capturing glycopeptides. Owing to the relatively large amount of residual vinyl groups introduced by DPP on the core surface, the VPBA monomer was coated with high efficiency, working as the shell. Moreover, the overall polymerization route, especially the use of DPP, made the synthesis of nanoparticles facile and time-saving. With the poly(MBA-co-MAA)@VPBA nanoparticles, 18 glycopeptides from horseradish peroxidase (HRP) digest were captured and identified by MALDI-TOF mass spectrometric analysis, relative to eight glycopeptides enriched by using commercially available meta-aminophenylboronic acid agarose under the same conditions. When the concentration of the HRP digest was decreased to as low as 5 nmol, glycopeptides could still be selectively isolated by the prepared nanoparticles. Our results demonstrated that the synthetic poly(MBA-co-MAA)@VPBA nanoparticles might be a promising selective enrichment material for glycoproteome analysis. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. LC-MS3 quantification of O-glycopeptides in human serum

    Czech Academy of Sciences Publication Activity Database

    Sanda, M.; Pompach, Petr; Benicky, J.; Goldman, R.

    2013-01-01

    Roč. 34, č. 16 (2013), s. 2342-2349 ISSN 0173-0835 R&D Projects: GA MŠk LH13051 Institutional support: RVO:61388971 Keywords : LC-MS3 * O-glycosylation * Quantification of glycopeptides Subject RIV: CE - Biochemistry Impact factor: 3.161, year: 2013

  13. Homoserine as an Aspartic Acid Precursor for Synthesis of Proteoglycan Glycopeptide Containing Aspartic Acid and a Sulfated Glycan Chain.

    Science.gov (United States)

    Yang, Weizhun; Ramadan, Sherif; Yang, Bo; Yoshida, Keisuke; Huang, Xuefei

    2016-12-02

    Among many hurdles in synthesizing proteoglycan glycopeptides, one challenge is the incorporation of aspartic acid in the peptide backbone and acid sensitive O-sulfated glycan chains. To overcome this, a new strategy was developed utilizing homoserine as an aspartic acid precursor. The conversion of homoserine to aspartic acid in the glycopeptide was successfully accomplished by late stage oxidation using (2,2,6,6-tetramethyl-piperidin-1-yl)oxyl (TEMPO) and bis(acetoxy)iodobenzene (BAIB). This is the first time that a glycopeptide containing aspartic acid and an O-sulfated glycan was synthesized.

  14. Status Report on the High-Throughput Characterization of Complex Intact O-Glycopeptide Mixtures

    Science.gov (United States)

    Pap, Adam; Klement, Eva; Hunyadi-Gulyas, Eva; Darula, Zsuzsanna; Medzihradszky, Katalin F.

    2018-05-01

    A very complex mixture of intact, human N- and O-glycopeptides, enriched from the tryptic digest of urinary proteins of three healthy donors using a two-step lectin affinity enrichment, was analyzed by LC-MS/MS, leading to approximately 45,000 glycopeptide EThcD spectra. Two search engines, Byonic and Protein Prospector, were used for the interpretation of the data, and N- and O-linked glycopeptides were assigned from separate searches. The identification rate was very low in all searches, even when results were combined. Thus, we investigated the reasons why was it so, to help to improve the identification success rate. Focusing on O-linked glycopeptides, we noticed that in EThcD, larger glycan oxonium ions better survive the activation than those in HCD. These fragments, combined with reducing terminal Y ions, provide important information about the glycan(s) present, so we investigated whether filtering the peaklists for glycan oxonium ions indicating the presence of a tetra- or hexasaccharide structure would help to reveal all molecules containing such glycans. Our study showed that intact glycans frequently do not survive even mild supplemental activation, meaning one cannot rely on these oxonium ions exclusively. We found that ETD efficiency is still a limiting factor, and for highly glycosylated peptides, the only information revealed in EThcD was related to the glycan structures. The limited overlap of results delivered by the two search engines draws attention to the fact that automated data interpretation of O-linked glycopeptides is not even close to being solved. [Figure not available: see fulltext.

  15. Cell surface glycopeptides from human intestinal epithelial cell lines derived from normal colon and colon adenocarcinomas

    International Nuclear Information System (INIS)

    Youakim, A.; Herscovics, A.

    1985-01-01

    The cell surface glycopeptides from an epithelial cell line (CCL 239) derived from normal human colon were compared with those from three cell lines (HCT-8R, HCT-15, and CaCo-2) derived independently from human colonic adenocarcinomas. Cells were incubated with D-[2- 3 H]mannose or L-[5,6- 3 H]fucose for 24 h and treated with trypsin to release cell surface components which were then digested exhaustively with Pronase and fractionated on Bio-Gel P-6 before and after treatment with endo-beta-N-acetylglucosaminidase H. The most noticeable difference between the labeled glycopeptides from the tumor and CCL 239 cells was the presence in the former of an endo-beta-N-acetylglucosaminidase H-resistant high molecular weight glycopeptide fraction which was eluted in the void volume of Bio-Gel P-6. This fraction was obtained with both labeled mannose and fucose as precursors. However, acid hydrolysis of this fraction obtained after incubation with [2- 3 H]mannose revealed that as much as 60-90% of the radioactivity was recovered as fucose. Analysis of the total glycopeptides (cell surface and cell pellet) obtained after incubation with [2- 3 H]mannose showed that from 40-45% of the radioactivity in the tumor cells and less than 10% of the radioactivity in the CCL 239 cells was recovered as fucose. After incubation of the HCT-8R cells with D-[1,6- 3 H]glucosamine and L-[1- 14 C]fucose, strong acid hydrolysis of the labeled glycopeptide fraction excluded from Bio-Gel P-6 produced 3 H-labeled N-acetylglucosamine and N-acetylgalactosamine

  16. Expert Panel Elicitation

    Energy Technology Data Exchange (ETDEWEB)

    Jensen, M. [Swedish Radiation Protection Authority, Stockholm (Sweden). Dept. of Waste Management and Environmental Protection; Hora, S.C. [Univ. of Hawaii, Hilo, HI (United States)

    2005-09-15

    Scientists are now frequently in a situation where data cannot be easily assessed, since they may have conflicting or uncertain sources. While expert judgment reflects private choices, it is possible both reduce the personal aspect as well as in crease confidence in the judgments by using formal protocols for choice and elicitation of experts. A full-scale elicitation made on seismicity following glaciation, now in its late phase and presented here in a preliminary form, illustrates the value of the technique and some essential issues in connection with the decision to launch such a project. The results show an unusual low variation between the experts.

  17. Eliciting Sound Memories.

    Science.gov (United States)

    Harris, Anna

    2015-11-01

    Sensory experiences are often considered triggers of memory, most famously a little French cake dipped in lime blossom tea. Sense memory can also be evoked in public history research through techniques of elicitation. In this article I reflect on different social science methods for eliciting sound memories such as the use of sonic prompts, emplaced interviewing, and sound walks. I include examples from my research on medical listening. The article considers the relevance of this work for the conduct of oral histories, arguing that such methods "break the frame," allowing room for collaborative research connections and insights into the otherwise unarticulatable.

  18. Elicited vs. voluntary promises

    NARCIS (Netherlands)

    Ismayilov, H.; Potters, Jan

    2017-01-01

    We set up an experiment with pre-play communication to study the impact of promise elicitation by trustors from trustees on trust and trustworthiness. When given the opportunity a majority of trustors solicits a promise from the trustee. This drives up the promise making rate by trustees to almost

  19. Homoserine as an Aspartic Acid Precursor for Synthesis of Proteoglycan Glycopeptide Containing Aspartic Acid and Sulfated Glycan Chain

    OpenAIRE

    Yang, Weizhun; Ramadan, Sherif; Yang, Bo; Yoshida, Keisuke; Huang, Xuefei

    2016-01-01

    Among many hurdles in synthesizing proteoglycan glycopeptides, one challenge is the incorporation of aspartic acid in the peptide backbone and acid sensitive O-sulfated glycan chains. To overcome this, a new strategy was developed utilizing homoserine as an aspartic acid precursor. The conversion of homoserine to aspartic acid in the glycopeptide was successfully accomplished by late stage oxidation using 2,2,6,6-tetramethyl-1-piperidinyloxy (TEMPO) and bis(acetoxy)iodobenzene (BAIB). This is...

  20. Feasibility study of Anti-MUC1 aptamer use as vector target director of 1,10 phenantrolin for radiosensitization of breast cancer cells; Estudo da viabilidade do uso do aptâmero Anti-MUC1 como vetor alvo direcionador de 1,10 fenantrolina para radio sensibilização de células de câncer de mama

    Energy Technology Data Exchange (ETDEWEB)

    Alves, Laís Nascimento

    2017-07-01

    With the rising incidence of cancer and this disease as global public health dilemma, there is an alarming need of studying new cancer therapies. To achieve the development of efficient agents is essential to understand the fundamental mechanisms of carcinogenesis and tumor progression. Overexpression of proteins in malignant tissues, in contrast to expression of the proteins found in normal tissues of the same organ, is crucially important and of great interest for the characterization of potential tumor biomarkers. Following this premise, MUC1 glycoprotein was selected as a therapeutic target in a breast cancer model. In order to determine the viability of the aptA aptamer as radiosensitizers carrier, the toxic compound 1,10 phenanthroline, complexed with Fe(II) was intercalated in the aptamers. The dissociation constant was found at a value of Kd = 30 μM. The selective binding and internalization of the compound was demonstrated. Based on these data, the aptA can be used as carrying vector of molecules such as 1,10-phenanthroline. As a next stage, the evaluation of its in vitro potential as radiosensitizers with the use of ionizing radiation will be done. (author)

  1. Adamantoylated biologically active small peptides and glycopeptides structurally related to the bacterial peptidoglycan.

    Science.gov (United States)

    Frkanec, Ruža; Vranešić, Branka; Tomić, Srdjanka

    2013-01-01

    A large number of novel synthetic compounds representing smaller parts of original peptidoglycan molecules have been synthesized and found to possess versatile biological activity, particularly immunomodulating properties. A series of compounds containing the adamantyl residues coupled to peptides and glycopeptides characteristic for bacterial peptidoglycan was described. The new adamantylpeptides and adamantylglycopeptides were prepared starting from N-protected racemic adamantylglycine and dipeptide L-Ala-D-isoglutamine. The adamantyl glycopeptides were obtained by coupling the adamantyltripeptides with alpha-D-mannose moiety through spacer molecule of fixed chirality. Since the starting material was D,L-(adamantyl-glycine) the condensation products with the dipeptide were mixtures of diastereoisomers. The obtained diastereoisomers were separated, characterized, and tested for immunostimulating activity. An HPLC method for purity testing was developed and adapted for the particular compounds.

  2. The efficacy and safety of linezolid and glycopeptides in the treatment of Staphylococcus aureus infections.

    Directory of Open Access Journals (Sweden)

    Jinjian Fu

    Full Text Available To assess the effectiveness and safety of linezolid in comparison with glycopeptides (vancomycin and teicoplanin for the treatment of Staphylococcus aureus infections, we conducted a meta-analysis of relevant randomized controlled trials. A thorough search of Pubmed and other databases was performed. Thirteen trials on 3863 clinically assessed patients were included. Linezolid was slightly more effective than glycopeptides in the intent-to-treat population (odds ratio [OR], 1.05; 95% confidence interval [CI], 1.01-1.10, was more effective in clinically assessed patients (OR 95% CI: 1.38, 1.17-1.64 and in all microbiologically assessed patients (OR 95% CI: 1.38, 1.15-1.65. Linezolid was associated with better treatment in skin and soft-tissue infections (SSTIs patients (OR 95% CI: 1.61, 1.22-2.12, but not in bacteraemia (OR 95% CI: 1.24, 0.78-1.97 or pneumonia (OR 95% CI: 1.25, 0.97-1.60 patients. No difference of mortality between linezolid and glycopeptides was seen in the pooled trials (OR 95% CI: 0.98, 0.83-1.15. While linezolid was associated with more haematological (OR 95% CI: 2.23, 1.07-4.65 and gastrointestinal events (OR 95% CI: 2.34, 1.53-3.59, a significantly fewer events of skin adverse effects (OR 95% CI: 0.27, 0.16-0.46 and nephrotoxicity (OR 95% CI: 0.45, 0.28-0.72 were recorded in linezolid. Based on the analysis of the pooled data of randomized control trials, linezolid should be a better choice for treatment of patients with S. aureus infections, especially in SSTIs patients than glycopeptides. However, when physicians choose to use linezolid, risk of haematological and gastrointestinal events should be taken into account according to the characteristics of the specific patient populations.

  3. Peptide and glycopeptide dendrimers and analogous dendrimeric structures and their biomedical applications

    Czech Academy of Sciences Publication Activity Database

    Šebestík, Jaroslav; Niederhafner, Petr; Ježek, Jan

    2011-01-01

    Roč. 40, č. 2 (2011), s. 301-370 ISSN 0939-4451 R&D Projects: GA ČR GA203/07/1517; GA AV ČR KAN200520703; GA AV ČR KAN200100801 Institutional research plan: CEZ:AV0Z40550506 Keywords : glycopeptide dendrimers * prions * drug and gene delivery * cancer * nanomedicine * nanotechnology * nanomaterials Subject RIV: CC - Organic Chemistry Impact factor: 3.248, year: 2011

  4. Multi-objective optimization of glycopeptide antibiotic production in batch and fed batch processes

    DEFF Research Database (Denmark)

    Maiti, Soumen K.; Eliasson Lantz, Anna; Bhushan, Mani

    2011-01-01

    batch operations using process model for Amycolatopsis balhimycina, a glycopeptide antibiotic producer. This resulted in a set of several pareto optimal solutions with the two objectives ranging from (0.75gl−1, 3.97g$-1) to (0.44gl−1, 5.19g$-1) for batch and from (1.5gl−1, 5.46g$-1) to (1.1gl−1, 6.34g...

  5. A randomized phase II study of immunization with dendritic cells modified with poxvectors encoding CEA and MUC1 compared with the same poxvectors plus GM-CSF for resected metastatic colorectal cancer.

    Science.gov (United States)

    Morse, Michael A; Niedzwiecki, Donna; Marshall, John L; Garrett, Christopher; Chang, David Z; Aklilu, Mebea; Crocenzi, Todd S; Cole, David J; Dessureault, Sophie; Hobeika, Amy C; Osada, Takuya; Onaitis, Mark; Clary, Bryan M; Hsu, David; Devi, Gayathri R; Bulusu, Anuradha; Annechiarico, Robert P; Chadaram, Vijaya; Clay, Timothy M; Lyerly, H Kim

    2013-12-01

    To determine whether 1 of 2 vaccines based on dendritic cells (DCs) and poxvectors encoding CEA (carcinoembryonic antigen) and MUC1 (PANVAC) would lengthen survival in patients with resected metastases of colorectal cancer (CRC). Recurrences after complete resections of metastatic CRC remain frequent. Immune responses to CRC are associated with fewer recurrences, suggesting a role for cancer vaccines as adjuvant therapy. Both DCs and poxvectors are potent stimulators of immune responses against cancer antigens. Patients, disease-free after CRC metastasectomy and perioperative chemotherapy (n = 74), were randomized to injections of autologous DCs modified with PANVAC (DC/PANVAC) or PANVAC with per injection GM-CSF (granulocyte-macrophage colony-stimulating factor). Endpoints were recurrence-free survival overall survival, and rate of CEA-specific immune responses. Clinical outcome was compared with that of an unvaccinated, contemporary group of patients who had undergone CRC metastasectomy, received similar perioperative therapy, and would have otherwise been eligible for the study. Recurrence-free survival at 2 years was similar (47% and 55% for DC/PANVAC and PANVAC/GM-CSF, respectively) (χ P = 0.48). At a median follow-up of 35.7 months, there were 2 of 37 deaths in the DC/PANVAC arm and 5 of 37 deaths in the PANVAC/GM-CSF arm. The rate and magnitude of T-cell responses against CEA was statistically similar between study arms. As a group, vaccinated patients had superior survival compared with the contemporary unvaccinated group. Both DC and poxvector vaccines have similar activity. Survival was longer for vaccinated patients than for a contemporary unvaccinated group, suggesting that a randomized trial of poxvector vaccinations compared with standard follow-up after metastasectomy is warranted. (NCT00103142).

  6. Automatic and rapid identification of glycopeptides by nano-UPLC-LTQ-FT-MS and proteomic search engine.

    Science.gov (United States)

    Giménez, Estela; Gay, Marina; Vilaseca, Marta

    2017-01-30

    Here we demonstrate the potential of nano-UPLC-LTQ-FT-MS and the Byonic™ proteomic search engine for the separation, detection, and identification of N- and O-glycopeptide glycoforms in standard glycoproteins. The use of a BEH C18 nanoACQUITY column allowed the separation of the glycopeptides present in the glycoprotein digest and a baseline-resolution of the glycoforms of the same glycopeptide on the basis of the number of sialic acids. Moreover, we evaluated several acquisition strategies in order to improve the detection and characterization of glycopeptide glycoforms with the maximum number of identification percentages. The proposed strategy is simple to set up with the technology platforms commonly used in proteomic labs. The method allows the straightforward and rapid obtention of a general glycosylated map of a given protein, including glycosites and their corresponding glycosylated structures. The MS strategy selected in this work, based on a gas phase fractionation approach, led to 136 unique peptides from four standard proteins, which represented 78% of the total number of peptides identified. Moreover, the method does not require an extra glycopeptide enrichment step, thus preventing the bias that this step could cause towards certain glycopeptide species. Data are available via ProteomeXchange with identifier PXD003578. We propose a simple and high-throughput glycoproteomics-based methodology that allows the separation of glycopeptide glycoforms on the basis of the number of sialic acids, and their automatic and rapid identification without prior knowledge of protein glycosites or type and structure of the glycans. Copyright © 2016 Elsevier B.V. All rights reserved.

  7. [Preparation of cysteine-click maltose modified silica as a hydrophilic interaction liquid chromatography material for the enrichment of glycopeptides].

    Science.gov (United States)

    Sun, Xudong; Zhang, Lingyi; Zhang, Weibing

    2017-07-08

    Because of the low abundance of glycoprotein and glycopeptide in complex biological samples, it is urgent to develop an efficient method for glycopeptide enrichment in comprehensive and in-depth glycoproteomes research. Herein, a novel hydrophilic silica was developed through surface modification with cysteine-click maltose (Cys-Mal@SiO 2 ). The developed hydrophilic silica was packed into a solid phase extraction (SPE) column, and applied to the highly selective enrichment and identification of N -linked glycopeptides. The Cys-Mal@SiO 2 demonstrated better identification capability over Cys@SiO 2 , Mal@SiO 2 and commercial hydrophilic interaction liquid chromatography (HILIC) in glycopeptide enrichment due to the synergistic effect of the two kinds of hydrophilic molecules. In the selective enrichment of tryptic digest from human immunoglobulin G, glycopeptides with higher signal-to-noises were detected by Cys-Mal@SiO 2 . In addition, 1551 unique glycopeptides with 906 N -glycosylation sites from 466 different N -linked glycoproteins were identified from the proteins extracted from mouse liver after the enrichment with Cys-Mal@SiO 2 . In contrast, the numbers of identified glycopeptides, glycoproteins and N -glycosylation sites identified by Cys@SiO 2 were 211, 67, 127 respectively less than by Cys-Mal@SiO 2 , and the corresponding numbers were 289, 76, 193 by Mal@SiO 2 . These results showed that the developed Cys-Mal@SiO 2 is a promising affinity material for N -glycoproteomics research of real complex biological samples.

  8. Highly Efficient Release of Glycopeptides from Hydrazide Beads by Hydroxylamine Assisted PNGase F Deglycosylation for N-Glycoproteome Analysis.

    Science.gov (United States)

    Huang, Junfeng; Wan, Hao; Yao, Yating; Li, Jinan; Cheng, Kai; Mao, Jiawei; Chen, Jin; Wang, Yan; Qin, Hongqiang; Zhang, Weibing; Ye, Mingliang; Zou, Hanfa

    2015-10-20

    Selective enrichment of glycopeptides from complex sample followed by cleavage of N-glycans by PNGase F to expose an easily detectable mark on the former glycosylation sites has become the popular protocol for comprehensive glycoproteome analysis. On account of the high enrichment specificity, hydrazide chemistry based solid-phase extraction of N-linked glycopeptides technique has sparked numerous interests. However, the enzymatic release of glycopeptides captured by hydrazide beads through direct incubation of the beads with PNGase F is not efficient due to the inherent steric hindrance effect. In this study, we developed a hydroxylamine assisted PNGase F deglycosylation (HAPD) method using the hydroxylamine to release glycopeptides captured on the hydrazide beads through the cleavage of hydrazone bonds by transamination followed with the PNGase F deglycosylation of the released glycopeptides in the free solution. Because of the homogeneous condition for the deglycosylation, the recovery of deglycosylated peptides (deglycopeptides) was improved significantly. It was found that 27% more N-glycosylation sites were identified by the HAPD strategy compared with the conventional method. Moreover, the ratio of identified N-terminal glycosylated peptides was improved over 5-fold.

  9. Facile synthesis of thiol-polyethylene glycol functionalized magnetic titania nanomaterials for highly efficient enrichment of N-linked glycopeptides.

    Science.gov (United States)

    Wang, Jiawen; Yao, Jizong; Sun, Nianrong; Deng, Chunhui

    2017-08-25

    As protein N-glycosylation involved in generation and development of various cancers and diseases, it is vital to capture glycopeptides from complex biological samples for biomarker discovery. In this work, by taking advantages of the interaction between titania and thiol groups, thiol-polyethylene glycol functionalized magnetic titania nanomaterials (denoted as Fe 3 O 4 @TiO 2 @PEG) were firstly fabricated as an excellent hydrophilic adsorbent of N-linked glycopeptides. On one hand, the special interaction of titanium-thiol makes the synthetic manipulation simple and provides a new idea for design and synthesis of novel nanomaterials; on the other hand, strong magnetic response could realize rapid separation and the outstanding hydrophilicity of polyethylene glycol makes Fe 3 O 4 @TiO 2 @PEG nanomaterials show superior performance for glycopeptides enrichment with ultralow limit of detection (0.1mol/μL) and high selectivity (1:100). As a result, 24 and 33 glycopeptides enriched from HRP and IgG digests were identified respectively by MALDI-TOF MS, and 300 glycopeptides corresponding to 106 glycoproteins were recognized from merely 2μL human serum, indicating a great potential of Fe 3 O 4 @TiO 2 @PEG nanomaterials for glycoproteomic research. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Members of the genera Paenibacillus and Rhodococcus harbor genes homologous to enterococcal glycopeptide resistance genes vanA and vanB

    DEFF Research Database (Denmark)

    Guardabassi, L.; Christensen, H.; Hasman, Henrik

    2004-01-01

    Genes homologous to enterococcal glycopeptide resistance genes vanA and vanB were found in glycopeptide-resistant Paenibacillus and Rhodococcus strains from soil. The putative D-Ala:D-Lac ligase genes in Paenibacillus thiaminolyticus PT-2B1 and Paenibacillus apiarius PA-B2B were closely related...

  11. Fluorographic detection of tritiated glycopeptides and oligosaccharides separated on polyacrylamide gels: analysis of glycans from Dictyostelium discoideum glycoproteins

    International Nuclear Information System (INIS)

    Prem Das, O.; Henderson, E.J.

    1986-01-01

    Previous workers have shown that oligosaccharides and glycopeptides can be separated by electrophoresis in buffers containing borate ions. However, normal fluorography of tritium-labeled structures cannot be performed because the glycans are soluble and can diffuse during equilibration with scintillants. This problem has been circumvented by equilibration of the gel with 2,5-diphenyloxazole (PPO) prior to electrophoresis. The presence of PPO in the gel during electrophoresis does not alter mobility of the glycopeptides and oligosaccharides. After electrophoresis, the gel is simply dried and fluorography performed. This allows sensitive and precise comparisons of labeled samples in parallel lanes of a slab gel and, since mobilities are highly reproducible, between different gels. The procedure is preparative in that after fluorography the gel bands can be quantitatively eluted for further study, without any apparent modification by the procedure. In this report, the procedure is illustrated by fractionation of both neutral and anionic glycopeptides produced by the cellular slime mold Dictyostelium discoideum

  12. 3-Aminoquinoline/p-coumaric acid as a MALDI matrix for glycopeptides, carbohydrates, and phosphopeptides.

    Science.gov (United States)

    Fukuyama, Yuko; Funakoshi, Natsumi; Takeyama, Kohei; Hioki, Yusaku; Nishikaze, Takashi; Kaneshiro, Kaoru; Kawabata, Shin-Ichirou; Iwamoto, Shinichi; Tanaka, Koichi

    2014-02-18

    Glycosylation and phosphorylation are important post-translational modifications in biological processes and biomarker research. The difficulty in analyzing these modifications is mainly their low abundance and dissociation of labile regions such as sialic acids or phosphate groups. One solution in matrix-assisted laser desorption/ionization (MALDI) mass spectrometry is to improve matrices for glycopeptides, carbohydrates, and phosphopeptides by increasing the sensitivity and suppressing dissociation of the labile regions. Recently, a liquid matrix 3-aminoquinoline (3-AQ)/α-cyano-4-hydroxycinnamic acid (CHCA) (3-AQ/CHCA), introduced by Kolli et al. in 1996, has been reported to increase sensitivity for carbohydrates or phosphopeptides, but it has not been systematically evaluated for glycopeptides. In addition, 3-AQ/CHCA enhances the dissociation of labile regions. In contrast, a liquid matrix 1,1,3,3-tetramethylguanidium (TMG, G) salt of p-coumaric acid (CA) (G3CA) was reported to suppress dissociation of sulfate groups or sialic acids of carbohydrates. Here we introduce a liquid matrix 3-AQ/CA for glycopeptides, carbohydrates, and phosphopeptides. All of the analytes were detected as [M + H](+) or [M - H](-) with higher or comparable sensitivity using 3-AQ/CA compared with 3-AQ/CHCA or 2,5-dihydroxybenzoic acid (2,5-DHB). The sensitivity was increased 1- to 1000-fold using 3-AQ/CA. The dissociation of labile regions such as sialic acids or phosphate groups and the fragmentation of neutral carbohydrates were suppressed more using 3-AQ/CA than using 3-AQ/CHCA or 2,5-DHB. 3-AQ/CA was thus determined to be an effective MALDI matrix for high sensitivity and the suppression of dissociation of labile regions in glycosylation and phosphorylation analyses.

  13. Molecular analysis of diverse elements mediating VanA glycopeptide resistance in enterococci

    DEFF Research Database (Denmark)

    Palepou, M.F.I.; Adebiyi, A.M.A.; Tremlett, C.H.

    1998-01-01

    Differences were examined among 24 distinct elements mediating VanA-type glycopeptide resistance in enterococci isolated from hospital patients and non-human sources in the UK. The methods used included long-PCR restriction fragment length polymorphism (L-PCR RFLP) analysis and DNA hybridization...... characterized by the presence of an IS1216V/IS3-like/orf1 complex and a point mutation in vanX, both of which were absent from the other 23 groups of VanA elements. This finding is consistent with the dissemination of a stable resistance element. We conclude that L-PCR RFLP analysis, combined with DNA...

  14. Macrophage galactose-type C-type lectin receptor for DC targeting of antitumor glycopeptide vaccines

    DEFF Research Database (Denmark)

    Nuti, M; Zizzari, I; Napoletano, C

    2011-01-01

    e13528 Background: Dendritic cells (DCs) are the most potent antigen presenting cells and are employed in cancer vaccination. Several receptors are being studied in order to identif strategies to increase DCs activating capacity. The C-type lectin macrophage galactose type C-type lectin (MGL...... of IFNg and IL-2 secretion by both CD8 and CD4 T cells. CONCLUSIONS: These results demonstrate that MGL engagement profoundly affects DC plasticity inducing and directing a Th1 immune response. Moreover, MGL receptor expressed on human DC can be targeted by glycopeptide based vaccines with adjuvant...

  15. vanO, a new glycopeptide resistance operon in environmental Rhodococcus equi isolates

    DEFF Research Database (Denmark)

    Gudeta, Dereje Dadi; Moodley, Arshnee; Bortolaia, Valeria

    2014-01-01

    We describe sequence and gene organization of a new glycopeptide resistance operon (vanO) in Rhodococcus equi from soil. The vanO operon has low homology to enterococccal van operons and harbors a vanHOX cluster transcribed in opposite direction to the vanS-vanR regulatory system and comprised be...... between three open reading frames with unknown function. This finding has clinical interest since glycopeptides are used to treat R. equi infections and resistance has been reported in clinical isolates....

  16. Constructive Preference Elicitation

    Directory of Open Access Journals (Sweden)

    Paolo Dragone

    2018-01-01

    Full Text Available When faced with large or complex decision problems, human decision makers (DM can make costly mistakes, due to inherent limitations of their memory, attention, and knowledge. Preference elicitation tools assist the decision maker in overcoming these limitations. They do so by interactively learning the DM’s preferences through appropriately chosen queries and suggesting high-quality outcomes based on the preference estimates. Most state-of-the-art techniques, however, fail in constructive settings, where the goal is to synthesize a custom or entirely novel configuration rather than choosing the best option among a given set of candidates. Many wide-spread problems are constructive in nature: customizing composite goods such as cars and computers, bundling products, recommending touristic travel plans, designing apartments, buildings, or urban layouts, etc. In these settings, the full set of outcomes is humongous and can not be explicitly enumerated, and the solution must be synthesized via constrained optimization. In this article, we describe recent approaches especially designed for constructive problems, outlining the underlying ideas and their differences as well as their limitations. In presenting them, we especially focus on novel issues that the constructive setting brings forth, such as how to deal with sparsity of the DM’s preferences, how to properly frame the interaction, and how to achieve efficient synthesis of custom instances.

  17. Isolation of N-linked glycopeptides by hydrazine-functionalized magnetic particles.

    Science.gov (United States)

    Sun, Shisheng; Yang, Ganglong; Wang, Ting; Wang, Qinzhe; Chen, Chao; Li, Zheng

    2010-04-01

    We introduce a novel combination of magnetic particles with hydrazine chemistry, dubbed as hydrazine-functionalized magnetic particles (HFMP) for isolation of glycopeptides. Four methods have been developed and compared for the production of HFMP by hydrazine modification of the surface of the carboxyl and epoxy-silanized magnetic particles, respectively. The evaluation of the capability and specificity of HFMP as well as the optimization of the coupling condition for capturing of glycoproteins were systematically investigated. The results showed that HFMP prepared by adipic dihydrazide functionalization from carboxyl-silanized magnetic particles (HFCA) displayed the maximum capture capacity and isolated efficiency for glycoprotein. When measured with glycoproteins, the capacity of the HFCA (1 g) for coupling bovine fetuin was 130 +/- 5.3 mg. The capability of this method was also confirmed by successful isolation of all formerly glycosylated peptides from standard glycoproteins and identification of their glycosylation sites, which demonstrated the feasibility of the HFCA as an alternative solid support for isolation of glycoproteins/glycopeptides.

  18. pGlyco 2.0 enables precision N-glycoproteomics with comprehensive quality control and one-step mass spectrometry for intact glycopeptide identification.

    Science.gov (United States)

    Liu, Ming-Qi; Zeng, Wen-Feng; Fang, Pan; Cao, Wei-Qian; Liu, Chao; Yan, Guo-Quan; Zhang, Yang; Peng, Chao; Wu, Jian-Qiang; Zhang, Xiao-Jin; Tu, Hui-Jun; Chi, Hao; Sun, Rui-Xiang; Cao, Yong; Dong, Meng-Qiu; Jiang, Bi-Yun; Huang, Jiang-Ming; Shen, Hua-Li; Wong, Catherine C L; He, Si-Min; Yang, Peng-Yuan

    2017-09-05

    The precise and large-scale identification of intact glycopeptides is a critical step in glycoproteomics. Owing to the complexity of glycosylation, the current overall throughput, data quality and accessibility of intact glycopeptide identification lack behind those in routine proteomic analyses. Here, we propose a workflow for the precise high-throughput identification of intact N-glycopeptides at the proteome scale using stepped-energy fragmentation and a dedicated search engine. pGlyco 2.0 conducts comprehensive quality control including false discovery rate evaluation at all three levels of matches to glycans, peptides and glycopeptides, improving the current level of accuracy of intact glycopeptide identification. The N-glycoproteome of samples metabolically labeled with 15 N/ 13 C were analyzed quantitatively and utilized to validate the glycopeptide identification, which could be used as a novel benchmark pipeline to compare different search engines. Finally, we report a large-scale glycoproteome dataset consisting of 10,009 distinct site-specific N-glycans on 1988 glycosylation sites from 955 glycoproteins in five mouse tissues.Protein glycosylation is a heterogeneous post-translational modification that generates greater proteomic diversity that is difficult to analyze. Here the authors describe pGlyco 2.0, a workflow for the precise one step identification of intact N-glycopeptides at the proteome scale.

  19. Glycopeptide Enrichment Using a Combination of ZIC-HILIC and Cotton Wool for Exploring the Glycoproteome of Wheat Flour Albumins

    DEFF Research Database (Denmark)

    Dedvisitsakul, Plaipol; Jacobsen, Susanne; Svensson, Birte

    2014-01-01

    Hydrophilic liquid chromatography (HILIC) is used extensively as a sample preparation step for glycopeptide enrichment in proteome research. Here, we have applied cotton wool and a zwitterionic HILIC (ZIC-HILIC) resin in solid-phase extraction microcolumns to provide a higher loading capacity...

  20. Semi-combinatorial approach for the preparation of linear comb-like glycopeptide dendrimers with Tn antigen using maleimide ligation

    Czech Academy of Sciences Publication Activity Database

    Vepřek, Pavel; Kelkar, S.; Trnka, T.; Hajdúch, M.; Ježek, Jan

    2002-01-01

    Roč. 8, - (2002), s. S127 ISSN 1075-2617. [European Peptide Symposium /27./. 31.08.2002-06.09.2002, Sorrento] R&D Projects: GA ČR GA303/01/0690 Institutional research plan: CEZ:AV0Z4055905 Keywords : glycopeptide Subject RIV: CE - Biochemistry

  1. Fabrication of Alkoxyamine-Functionalized Magnetic Core-Shell Microspheres via Reflux Precipitation Polymerization for Glycopeptide Enrichment

    Directory of Open Access Journals (Sweden)

    Meng Yu

    2016-03-01

    Full Text Available As a facile method to prepare hydrophilic polymeric microspheres, reflux precipitation polymerization has been widely used for preparation of polymer nanogels. In this article, we synthesized a phthalamide-protected N-aminooxy methyl acrylamide (NAMAm-p for preparation of alkoxyamine-functionalized polymer composite microspheres via reflux precipitation polymerization. The particle size and functional group density of the composite microspheres could be adjusted by copolymerization with the second monomers, N-isopropyl acrylamide, acrylic acid or 2-hydroxyethyl methacrylate. The resultant microspheres have been characterized by TEM, FT-IR, TGA and DLS. The experimental results showed that the alkoxyamine group density of the microspheres could reach as high as 1.49 mmol/g, and these groups showed a great reactivity with ketone/aldehyde compounds. With the aid of magnetic core, the hybrid microspheres could capture and magnetically isolate glycopeptides from the digested mixture of glycopeptides and non-glycopeptides at a 1:100 molar ratio. After that, we applied the composite microspheres to profile the glycol-proteome of a normal human serum sample, 95 unique glycopeptides and 64 glycoproteins were identified with these enrichment substrates in a 5 μL of serum sample.

  2. Direct analysis of site-specific N-glycopeptides of serological proteins in dried blood spot samples.

    Science.gov (United States)

    Choi, Na Young; Hwang, Heeyoun; Ji, Eun Sun; Park, Gun Wook; Lee, Ju Yeon; Lee, Hyun Kyoung; Kim, Jin Young; Yoo, Jong Shin

    2017-08-01

    Dried blood spot (DBS) samples have a number of advantages, especially with respect to ease of collection, transportation, and storage and to reduce biohazard risk. N-glycosylation is a major post-translational modification of proteins in human blood that is related to a variety of biological functions, including metastasis, cell-cell interactions, inflammation, and immunization. Here, we directly analyzed tryptic N-glycopeptides from glycoproteins in DBS samples using liquid chromatography-tandem mass spectrometry (LC-MS/MS) without centrifugation of blood samples, depletion of major proteins, desalting of tryptic peptides, and enrichment of N-glycopeptides. Using this simple method, we identified a total of 41 site-specific N-glycopeptides from 16 glycoproteins in the DBS samples, from immunoglobulin gamma 1 (IgG-1, 10 mg/mL) down to complement component C7 (50 μg/mL). Of these, 32 N-glycopeptides from 14 glycoproteins were consistently quantified over 180 days stored at room temperature. The major abundant glycoproteins in the DBS samples were IgG-1 and IgG-2, which contain nine asialo-fucosylated complex types of 16 different N-glycopeptide isoforms. Sialo-non-fucosylated complex types were primarily detected in the other glycoproteins such as alpha-1-acid glycoprotein 1, 2, alpha-1-antitypsin, alpha-2-macroglobulin, haptoglobin, hemopexin, Ig alpha 1, 2 chain C region, kininogen-1, prothrombin, and serotransferrin. We first report the characterization of site-specific N-glycoproteins in DBS samples by LC-MS/MS with minimal sample preparation.

  3. Antimicrobial resistance (AMR) nanomachines-mechanisms for fluoroquinolone and glycopeptide recognition, efflux and/or deactivation.

    Science.gov (United States)

    Phillips-Jones, Mary K; Harding, Stephen E

    2018-04-01

    In this review, we discuss mechanisms of resistance identified in bacterial agents Staphylococcus aureus and the enterococci towards two priority classes of antibiotics-the fluoroquinolones and the glycopeptides. Members of both classes interact with a number of components in the cells of these bacteria, so the cellular targets are also considered. Fluoroquinolone resistance mechanisms include efflux pumps (MepA, NorA, NorB, NorC, MdeA, LmrS or SdrM in S. aureus and EfmA or EfrAB in the enterococci) for removal of fluoroquinolone from the intracellular environment of bacterial cells and/or protection of the gyrase and topoisomerase IV target sites in Enterococcus faecalis by Qnr-like proteins. Expression of efflux systems is regulated by GntR-like (S. aureus NorG), MarR-like (MgrA, MepR) regulators or a two-component signal transduction system (TCS) (S. aureus ArlSR). Resistance to the glycopeptide antibiotic teicoplanin occurs via efflux regulated by the TcaR regulator in S. aureus. Resistance to vancomycin occurs through modification of the D-Ala-D-Ala target in the cell wall peptidoglycan and removal of high affinity precursors, or by target protection via cell wall thickening. Of the six Van resistance types (VanA-E, VanG), the VanA resistance type is considered in this review, including its regulation by the VanSR TCS. We describe the recent application of biophysical approaches such as the hydrodynamic technique of analytical ultracentrifugation and circular dichroism spectroscopy to identify the possible molecular effector of the VanS receptor that activates expression of the Van resistance genes; both approaches demonstrated that vancomycin interacts with VanS, suggesting that vancomycin itself (or vancomycin with an accessory factor) may be an effector of vancomycin resistance. With 16 and 19 proteins or protein complexes involved in fluoroquinolone and glycopeptide resistances, respectively, and the complexities of bacterial sensing mechanisms that

  4. Distinctive and Complementary MS2 Fragmentation Characteristics for Identification of Sulfated Sialylated N-Glycopeptides by nanoLC-MS/MS Workflow

    Science.gov (United States)

    Kuo, Chu-Wei; Guu, Shih-Yun; Khoo, Kay-Hooi

    2018-04-01

    High sensitivity identification of sulfated glycans carried on specific sites of glycoproteins is an important requisite for investigation of molecular recognition events involved in diverse biological processes. However, aiming for resolving site-specific glycosylation of sulfated glycopeptides by direct LC-MS2 sequencing is technically most challenging. Other than the usual limiting factors such as lower abundance and ionization efficiency compared to analysis of non-glycosylated peptides, confident identification of sulfated glycopeptides among the more abundant non-sulfated glycopeptides requires additional considerations in the selective enrichment and detection strategies. Metal oxide has been applied to enrich phosphopeptides and sialylated glycopeptides, but its use to capture sulfated glycopeptides has not been investigated. Likewise, various complementary MS2 fragmentation modes have yet to be tested against sialylated and non-sialylated sulfoglycopeptides due to limited appropriate sample availability. In this study, we have investigated the feasibility of sequencing tryptic sulfated N-glycopeptide and its MS2 fragmentation characteristics by first optimizing the enrichment methods to allow efficient LC-MS detection and MS2 analysis by a combination of CID, HCD, ETD, and EThcD on hybrid and tribrid Orbitrap instruments. Characteristic sulfated glyco-oxonium ions and direct loss of sulfite from precursors were detected as evidences of sulfate modification. It is anticipated that the technical advances demonstrated in this study would allow a feasible extension of our sulfoglycomic analysis to sulfoglycoproteomics. [Figure not available: see fulltext.

  5. Elicitation of ostomy pouch preferences

    DEFF Research Database (Denmark)

    Bonnichsen, Ole

    2011-01-01

    Background: Previous studies about patients who have undergone ostomy surgery commonly address the issues of the surgery, complications, preoperative counseling, quality of life, and psychosocial changes following surgery. Only a limited number of studies deal with how technical improvements...... in stoma care would affect patients and, to the author's knowledge, the present study is the first to elicit preferences for potential improvements in ostomy pouches in the form of monetary values. Objective: This article examines and measures Swedish patients' preferences for potential improvements...... in ostomy pouch attributes. The theory, study design, elicitation procedure, and resulting preference structure of the sample is described. Methods: A discrete-choice experiment (DCE) was used to elicit preferences. Respondents were asked to choose between alternatives in choice sets, in which each...

  6. Structural elucidation of the polysaccharide moiety of a glycopeptide (GLPCW-II) from Ganoderma lucidum fruiting bodies.

    Science.gov (United States)

    Ye, LiBin; Zhang, JingSong; Ye, XiJun; Tang, QingJiu; Liu, YanFang; Gong, ChunYu; Du, XiuJui; Pan, YingJie

    2008-03-17

    A water-soluble glycopeptide (GLPCW-II) was isolated from the fruiting bodies of Ganoderma lucidum by DEAE-Sepharose Fast-Flow and Sephacryl S-300 High Resolution Chromatography. The glycopeptide had a molecular weight of 1.2x10(4)Da (determined by HPLC), and consisted of approximately 90% carbohydrate and approximately 8% protein as determined using the phenol-sulfuric acid method and the BCA protein assay reagent kit, respectively. The polysaccharide moiety was composed mainly of D-Glc, L-Fuc, and D-Gal in the ratio of 1.00:1.09:4.09. To facilitate structure-activity studies, the structure of the GLPCW-II polysaccharide moiety was elucidated using 1H and 13C NMR spectroscopy including COSY, TOCSY, HMBC, HSQC, and ROESY, combined with GC-MS of methylated derivatives, and shown to consist of repeating units with the following structure: [Formula: see text].

  7. Absolute Quantitation of Glycoforms of Two Human IgG Subclasses Using Synthetic Fc Peptides and Glycopeptides

    Science.gov (United States)

    Roy, Rini; Ang, Evelyn; Komatsu, Emy; Domalaon, Ronald; Bosseboeuf, Adrien; Harb, Jean; Hermouet, Sylvie; Krokhin, Oleg; Schweizer, Frank; Perreault, Hélène

    2018-05-01

    Immunoglobulins, such as immunoglobulin G (IgG), are of prime importance in the immune system. Polyclonal human IgG comprises four subclasses, of which IgG1 and IgG2 are the most abundant in healthy individuals. In an effort to develop an absolute MALDI-ToF-MS quantitative method for these subclasses and their Fc N-glycoforms, (glyco)peptides were synthesized using a solid-phase approach and used as internal standards. Tryptic digest glycopeptides from monoclonal IgG1 and IgG2 samples were first quantified using EEQYN(GlcNAc)STYR and EEQFN(GlcNAc)STFR standards, respectively. For IgG1, a similar glycopeptide where tyrosine (Y) was isotopically labelled was used to quantify monoclonal IgG1 that had been treated with the enzyme Endo-F2, i.e., yielding tryptic glycopeptide EEQYN(GlcNAc)STYR. The next step was to quantify single subclasses within polyclonal human IgG samples. Although ion abundances in the MALDI spectra often showed higher signals for IgG2 than IgG1, depending on the spotting solvent used, determination of amounts using the newly developed quantitative method allowed to obtain accurate concentrations where IgG1 species were predominant. It was observed that simultaneous analysis of IgG1 and IgG2 yielded non-quantitative results and that more success was obtained when subclasses were quantified one by one. More experiments served to assess the respective extraction and ionization efficiencies of EEQYNSTYR/EEQFNSTFR and EEQYN(GlcNAc)STYR/EEQFN(GlcNAc)STFR mixtures under different solvent and concentration conditions.

  8. High-yield secretion of recombinant proteins expressed in tobacco cell culture with a designer glycopeptide tag: Process development.

    Science.gov (United States)

    Zhang, Ningning; Gonzalez, Maria; Savary, Brett; Xu, Jianfeng

    2016-03-01

    Low-yield protein production remains the most significant economic hurdle with plant cell culture technology. Fusions of recombinant proteins with hydroxyproline-O-glycosylated designer glycopeptide tags have consistently boosted secreted protein yields. This prompted us to study the process development of this technology aiming to achieve productivity levels necessary for commercial viability. We used a tobacco BY-2 cell culture expressing EGFP as fusion with a glycopeptide tag comprised of 32 repeat of "Ser-Pro" dipeptide, or (SP)32 , to study cell growth and protein secretion, culture scale-up, and establishment of perfusion cultures for continuous production. The BY-2 cells accumulated low levels of cell biomass (~7.5 g DW/L) in Schenk & Hildebrandt medium, but secreted high yields of (SP)32 -tagged EGFP (125 mg/L). Protein productivity of the cell culture has been stable for 6.0 years. The BY-2 cells cultured in a 5-L bioreactor similarly produced high secreted protein yield at 131 mg/L. Successful operation of a cell perfusion culture for 30 days was achieved under the perfusion rate of 0.25 and 0.5 day(-1) , generating a protein volumetric productivity of 17.6 and 28.9 mg/day/L, respectively. This research demonstrates the great potential of the designer glycopeptide technology for use in commercial production of valuable proteins with plant cell cultures. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. A fluorescent glycosyl-imprinted polymer for pH and temperature regulated sensing of target glycopeptide antibiotic.

    Science.gov (United States)

    Chen, Kuncai; He, Rong; Luo, Xiaoyan; Qin, Pengzhe; Tan, Lei; Tang, Youwen; Yang, Zhicong

    2017-08-15

    This paper demonstrates a new strategy for developing a fluorescent glycosyl-imprinted polymer for pH and temperature regulated sensing of target glycopeptide antibiotic. The technique provides amino modified Mn-doped ZnS QDs as fluorescent supports, 4-vinylphenylbronic acid as a covalent monomer, N-isopropyl acrylamide as a thermo-responsive monomer in combination with acrylamide as a non-covalent monomer, and glycosyl moiety of a glycopeptide antibiotic as a template to produce fluorescent molecularly imprinted polymer (FMIP) in aqueous solution. The FMIP can alter its functional moieties and structure with pH and temperature stimulation. This allows recognition of target molecules through control of pH and temperature. The fluorescence intensity of the FMIP was enhanced gradually as the concentration of telavancin increased, and showed selective recognition toward the target glycopeptide antibiotic preferentially among other antibiotics. Using the FMIP as a sensing material, good linear correlations were obtained over the concentration range of 3.0-300.0μg/L and with a low limit of detection of 1.0μg/L. The analysis results of telavancin in real samples were consistent with that obtained by liquid chromatography tandem mass spectrometry. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Elicitation threshold of cobalt chloride

    DEFF Research Database (Denmark)

    Fischer, Louise A; Johansen, Jeanne D; Voelund, Aage

    2016-01-01

    : On the basis of five included studies, the ED10 values of aqueous cobalt chloride ranged between 0.0663 and 1.95 µg cobalt/cm(2), corresponding to 30.8-259 ppm. CONCLUSIONS: Our analysis provides an overview of the doses of cobalt that are required to elicit allergic cobalt contactdermatitis in sensitized...

  11. Synthesis of 2-nitroimidazole-glycopeptide 68Ga-labeled for identification of areas of hypoxia in the tumor microenvironment

    International Nuclear Information System (INIS)

    Pérez Nario, Arian; Leiria Campo, Vanessa; Soares Bernardes, Emerson

    2016-01-01

    Introduction: Hypoxia is a pathological condition characterized by a reduction in oxygen delivery to a tissue or cell specific. It is estimated that 60% of solid tumors in advanced stages have areas of hypoxia and anoxia (almost complete absence of oxygen). It is now known that hypoxia in the tumor microenvironment is closely related to: 1) increased tumor aggressiveness; 2) increased relapse rate; 3) increased resistance to chemotherapy and radiotherapy; 4) poor prognosis of the disease. Therefore the use of non-invasive methods for the identification and quantification of areas of hypoxia in the tumor are extremely important for treating various types of cancers, allowing the use of individualized treatment strategies. Gallium-68 is a radionuclide widely used for positron emission tomography due to the availability of the generator 68 Ge / 68 Ga. With the aim of developing a new potential radiopharmaceutical 68 Ga-labeled for imaging hypoxia, it has been synthesized a new derivative of 2-nitroimidazole. Methods: The new glycopeptide derivative of 2-nitroimidazole was obtained by coupling the derivative of acetic acid 2-nitroimidazole with a glycopeptide obtained by solid phase synthesis, was subsequently conjugated with the chelating agent DOTA-NHS for labeling with the radionuclide 68 Ga . preparation and 68 Ga-labeled glycopeptide optimization marking with respect to solvent, time and temperature was made; also the radiochemical purity was assessed by reversed phase HPLC. Comparison with 18 F-FAZA, radiopharmaceutical used worldwide is also presented. Results: The new glycopeptide conjugate DOTA was conducted successfully synthesized and analyzed by mass spectrometry. Labeling with 68 Ga reached a maximum radiochemical purity of 96.6 ± 0.4% when 15μg glycopeptide was dissolved in 0.2 mL of acetonitrile, chloride 68Ga (5mCi) was evaporated to dryness and reconstituted in 0.1 mL of sterile water at room temperature, followed by heating to 95 ° C for 15 min. In

  12. 99mTc-glycopeptide: Synthesis, biodistribution and imaging in breast tumor-bearing rodents

    International Nuclear Information System (INIS)

    Wei, I-C.; Tsao Ning; Huang Yahui; Ho Yensheng; Wu Chungchin; Yu Dongfang; Yang, David J.

    2008-01-01

    This study was aimed to develop a glycopeptide (GP) to be used as a carrier for anti-cancer drug delivery. GP was synthesized by conjugating glutamate peptide and chitosan using carbodiimide as a coupling agent. Elemental analysis and capillary electrophoresis confirmed the purity was >95%. GP was labeled with sodium pertechnetate (Na 99m TcO 4 ) for in vitro and in vivo studies. Rhenium-GP was synthesized to support the binding site of 99m Tc at the glutamate positions 3-5. In vitro cellular uptake of 99m Tc-GP was performed in breast cancer cells. Cytosol had 60% whereas nucleus had 40% uptake of 99m Tc-GP. When cancer cells were incubated with glutamate or aspartate, followed by 99m Tc-GP, there was decreased uptake in cells treated with glutamate but not aspartate. The findings indicated that cellular uptake of 99m Tc-GP was via glutamate transporters. In addition, 99m Tc-GP was able to measure uptake differences after cells treated with paclitaxel. Biodistribution and planar imaging were conducted in breast tumor-bearing rats. Biodistribution of 99m Tc-GP showed increased tumor-to-tissue ratios as a function of time. Planar images confirmed that 99m Tc-GP could assess tumor uptake changes after paclitaxel treatment. In vitro and in vivo studies indicated that GP could target tumor cells, thus, GP may be a useful carrier for anti-cancer drug delivery

  13. Characterization of a novel antibacterial glycopeptide produced by Penicillium sp. M03.

    Science.gov (United States)

    Yang, W H; Zhang, W C; Lu, X M; Jiang, G S; Gao, P J

    2009-04-01

    To isolate a novel antibiotic termed AF from fermentation broth of Penicillium sp. M03 and to examine its antimicrobial activity, biological properties and structure characteristics. Sephadex LH-20 and HPLC were used to purify AF from fermentation broth of Penicillium sp. M03. The antimicrobial activity of AF was evaluated with the agar diffusion test. Amino acid and monosaccharide composition of AF was analysed by a HITACHI 835 detector and HPLC assay, respectively. Matrix-assisted laser desorption time of flight mass spectrometry, FT-IR and (1)H nuclear magnetic resonance spectra analyses were performed to examine the initial structure of AF. Eighty milligrams of AF was isolated as white powder from 1-l Penicillium sp. M03 fermentation broth. It consists of five amino acid and two monosaccharide residues and the molecular weight of it was 1017, and it was stable to beta-lactamase, heat, acid and alkali. AF showed inhibitory activity to a wide range of bacteria, particularly to multidrug-resistant Staphylococcus aureus. AF was a novel antibacterial glycopeptide with a broad inhibitory spectrum to pathogenic bacteria including multidrug-resistant agents. Furthermore, it is difficult to generate bacteria resistant to AF. Characterization of AF made it a potential antibiotic to fight against antibiotic-resistant bacterial pathogens.

  14. Study on oxidative metabolism of S180 cells induced by meretrix glycopeptide

    Science.gov (United States)

    Wu, Jielian; Wang, Ping; Kang, Huizhu

    2017-03-01

    Previous in vitro researches have showed that MGP0501, a natural glycopeptide isolated from Meretrix meretrix, can inhibit proliferation or induce apoptosis in human gastric carcinoma, lung cance (A549), Leukemia K562, mouse melanoma B16, hepatoma or breast cancer cells (MDA-MB-231). In this study, we performed an in vivo study to investigate the anti-tumor effect and mechanisms of MGP0501 on xenografted sarcoma 180 (S180) in mice. Results revealed that the inhibition rates of S180 on solid tumors were 69.72%, with a concentration of 6 mg/kg MGP0501,which was significantly higher than that of CTX. In addition, the biochemical metabolism analysis showed that MGP0501 could enhance the activities of glutathione tablets (GSH-Px) and catalase (CAT) and supersxide dismutase (SOD) in liver of mice. The content of malondialdehyde (MDA) in liver, on the contrary, was decreased. The promotion to antioxidation and the elimination of free radical in liver also attribute the antitumor activity of MGP0501. These results indicated that in vivo antitumor activity is associated with enhanced antioxidant capacity in S180 xenografts-bearing mice.

  15. The improvement of M1 polarization in macrophages by glycopeptide derived from Ganoderma lucidum.

    Science.gov (United States)

    Sun, Li-Xin; Lin, Zhi-Bin; Lu, Jie; Li, Wei-Dong; Niu, Yan-Dong; Sun, Yu; Hu, Chen-Yang; Zhang, Guo-Qiang; Duan, Xin-Suo

    2017-06-01

    Ganoderma lucidum (Fr.) Karst (Ganodermataceae) is a medicinal mushroom that has been extensively used in China for centuries to promote longevity and improve vigor without significant adverse effects. There is continuous interest in the bioactive properties of G. lucidum in view of its newly developed popularity in other regions besides Asia, such as Europe. Glycopeptide derived from G. lucidum (Gl-PS) is one of the main effective components isolated from this mushroom. The Gl-PS has been demonstrated pleiotropic with many bioactivities including immunomodulatory and antitumor effects. Macrophages are important cells involved in innate and adaptive immunity. Classically activated macrophages (M1) and alternatively activated macrophages (M2), with their different roles, display distinct cytokine profiles: M1 preferentially produces TNF-α, IL-6, and IL-12; conversely, M2 generates more IL-10 and arginase. Gl-PS might have the potential to promote macrophage M1 polarization by lipopolysaccharide (LPS). In this study, LPS was used to induce the M1 polarization. It was shown that the level of the TNF-α, IL-6, and IL-12 were increased and the IL-10 and arginase I were decreased in the polarized M1 macrophages after application of Gl-PS compared to the control. The results indicated the potential of Gl-PS to promote M1 polarization vs M2, with the health beneficial understanding of the bioactivities of Gl-PS.

  16. Site-specific glycoprofiling of N-linked glycopeptides using MALDI-TOF MS: strong correlation between signal strength and glycoform quantities

    DEFF Research Database (Denmark)

    Thaysen-Andersen, Morten; Mysling, Simon; Højrup, Peter

    2009-01-01

    Site-specific glycoprofiling of N-linked glycopeptides using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) is an emerging technique, but its quantitative accuracy lacks documentation. Thus, a systematic study of widely different glycopeptides was perf......Site-specific glycoprofiling of N-linked glycopeptides using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) is an emerging technique, but its quantitative accuracy lacks documentation. Thus, a systematic study of widely different glycopeptides...... was performed to determine the relationship between the relative abundances of the individual glycoforms and the MALDI-TOF MS signal strength. Glycopeptides derived from glycoproteins containing neutral glycans (ribonuclease B, IgG, and ovalbumin) were initially profiled and yielded excellent and reproducible...... quantitation (correlation coefficient r = 0.9958, n = 5) when evaluated against a normal phase HPLC 2-AB glycan profile. Similarly, precise quantitation was observed for various forms of N-glycans (free, permethylated, and fluorescence-labeled) using MS. In addition, three different sialoglycopeptides from...

  17. Emotion Eliciting in Affective Design

    DEFF Research Database (Denmark)

    Lai, Yoke Chin

    2014-01-01

    A successful product needs the designer’s conceptual model congruent with the user’s mental model. The fundamental affective design principle also applies to assistive product design. Eliciting effectively the user’s mental model has been a big challenge for most novice designers. This paper outl...... with 3D digital prototype as emotion stimulus. To form a closed loop reflective model, the emotion response from the user is assessed with an emotion assessment tool. Emotion ontology is established to form the backbone of the emotion assessment tool....

  18. Direct glycan structure determination of intact N-linked glycopeptides by low-energy collision-induced dissociation tandem mass spectrometry and predicted spectral library searching.

    Science.gov (United States)

    Pai, Pei-Jing; Hu, Yingwei; Lam, Henry

    2016-08-31

    Intact glycopeptide MS analysis to reveal site-specific protein glycosylation is an important frontier of proteomics. However, computational tools for analyzing MS/MS spectra of intact glycopeptides are still limited and not well-integrated into existing workflows. In this work, a new computational tool which combines the spectral library building/searching tool, SpectraST (Lam et al. Nat. Methods2008, 5, 873-875), and the glycopeptide fragmentation prediction tool, MassAnalyzer (Zhang et al. Anal. Chem.2010, 82, 10194-10202) for intact glycopeptide analysis has been developed. Specifically, this tool enables the determination of the glycan structure directly from low-energy collision-induced dissociation (CID) spectra of intact glycopeptides. Given a list of possible glycopeptide sequences as input, a sample-specific spectral library of MassAnalyzer-predicted spectra is built using SpectraST. Glycan identification from CID spectra is achieved by spectral library searching against this library, in which both m/z and intensity information of the possible fragmentation ions are taken into consideration for improved accuracy. We validated our method using a standard glycoprotein, human transferrin, and evaluated its potential to be used in site-specific glycosylation profiling of glycoprotein datasets from LC-MS/MS. In addition, we further applied our method to reveal, for the first time, the site-specific N-glycosylation profile of recombinant human acetylcholinesterase expressed in HEK293 cells. For maximum usability, SpectraST is developed as part of the Trans-Proteomic Pipeline (TPP), a freely available and open-source software suite for MS data analysis. Copyright © 2016 Elsevier B.V. All rights reserved.

  19. Characterization of Glycan Structures of Chondroitin Sulfate-Glycopeptides Facilitated by Sodium Ion-Pairing and Positive Mode LC-MS/MS

    Science.gov (United States)

    Nilsson, Jonas; Noborn, Fredrik; Gomez Toledo, Alejandro; Nasir, Waqas; Sihlbom, Carina; Larson, Göran

    2017-02-01

    Purification and liquid chromatography-tandem mass spectrometry (LC-MS/MS) characterization of glycopeptides, originating from protease digests of glycoproteins, enables site-specific analysis of protein N- and O-glycosylations. We have described a protocol to enrich, hydrolyze by chondroitinase ABC, and characterize chondroitin sulfate-containing glycopeptides (CS-glycopeptides) using positive mode LC-MS/MS. The CS-glycopeptides, originating from the Bikunin proteoglycan of human urine samples, had ΔHexAGalNAcGlcAGalGalXyl- O-Ser hexasaccharide structure and were further substituted with 0-3 sulfate and 0-1 phosphate groups. However, it was not possible to exactly pinpoint sulfate attachment residues, for protonated precursors, due to extensive fragmentation of sulfate groups using high-energy collision induced dissociation (HCD). To circumvent the well-recognized sulfate instability, we now introduced Na+ ions to form sodiated precursors, which protected sulfate groups from decomposition and facilitated the assignment of sulfate modifications. Sulfate groups were pinpointed to both Gal residues and to the GalNAc of the hexasaccharide structure. The intensities of protonated and sodiated saccharide oxonium ions were very prominent in the HCD-MS2 spectra, which provided complementary structural analysis of sulfate substituents of CS-glycopeptides. We have demonstrated a considerable heterogeneity of the bikunin CS linkage region. The realization of these structural variants should be beneficial in studies aimed at investigating the importance of the CS linkage region with regards to the biosynthesis of CS and potential interactions to CS binding proteins. Also, the combined use of protonated and sodiated precursors for positive mode HCD fragmentation analysis will likely become useful for additional classes of sulfated glycopeptides.

  20. Eliciting Spill: A methodological note

    Directory of Open Access Journals (Sweden)

    Alvita Nathaniel, Ph.D.

    2008-03-01

    Full Text Available Classic grounded theory is an inductive process that focuses on the experiences and perceptions of research participants (Glaser, 1978, 1998. Although grounded theorists may utilize other types of data, most are likely to gather information through qualitative interviews. The theorist seeks to understand what is going on as people resolve their main concern in a given substantive area. People know what is important to them and most want to tell their stories. They feel encouraged to talk when they recognize that their stories are valued. Once the informant realizes that he or she is being heard, the story flows. This is what Glaser refers to as “spill.” When this occurs, the theorist becomes a vessel to receive the story. As Glaser describes it, “The researcher will become a ‘big ear’ to pour into incessantly” (1998, p. 124. But, as easy as this seems, the researcher must overcome certain positivist tendencies to allow this to happen. Rather than asking a list of pre-planned questions, the grounded theorist will try to develop one question that will trigger the telling of a story. Eliciting spill requires a deliberate process that employs a deep understanding of the fundamentals of classic grounded theory. Derived from Glaser’s writings, the following are suggestions intended to help the novice grounded theorist to elicit spill.

  1. Quinolone and glycopeptide therapy for infection in mouse following exposure to mixed-field neutron-γ-photon radiation

    International Nuclear Information System (INIS)

    Brook, I.; Tom, S.P.; Ledney, G.D.

    1993-01-01

    The effects of increased doses of mixed-field neutron-γ-photon irradiation on bacterial translocation and subsequent sepsis, and the influence of antimicrobial therapy on these events, were studied in the C3H/HeN mouse. The results demonstrate a relationship between the doses of mixed-field radiation and the rates of infection due to Enterobacteriaceae. While L-ofloxacin therapy reduces the infection rate, prolongs survival and prevents mortality, the addition of a glycopeptide can enhance systemic infection by resistant bacteria in the irradiated host. (author)

  2. Quinolone and glycopeptide therapy for infection in mouse following exposure to mixed-field neutron-[gamma]-photon radiation

    Energy Technology Data Exchange (ETDEWEB)

    Brook, I. (Naval Medical Research Inst., Bethesda, MD (United States) Armed Forces Radiobiology Research Inst., Bethesda, MD (United States)); Tom, S.P.; Ledney, G.D. (Armed Forces Radiobiology Research Inst., Bethesda, MD (United States))

    1993-12-01

    The effects of increased doses of mixed-field neutron-[gamma]-photon irradiation on bacterial translocation and subsequent sepsis, and the influence of antimicrobial therapy on these events, were studied in the C3H/HeN mouse. The results demonstrate a relationship between the doses of mixed-field radiation and the rates of infection due to Enterobacteriaceae. While L-ofloxacin therapy reduces the infection rate, prolongs survival and prevents mortality, the addition of a glycopeptide can enhance systemic infection by resistant bacteria in the irradiated host. (author).

  3. Development of 68Ga-Glycopeptide as an Imaging Probe for Tumor Angiogenesis

    Directory of Open Access Journals (Sweden)

    Ning Tsao

    2011-01-01

    Full Text Available Objective. This study was aimed to study tissue distribution and tumor imaging potential of 68Ga-glycopeptide (GP in tumor-bearing rodents by PET. Methods. GP was synthesized by conjugating glutamate peptide and chitosan. GP was labeled with 68Ga chloride for in vitro and in vivo studies. Computer outlined region of interest (counts per pixel of the tumor and muscle (at the symmetric site was used to determine tumor-to-muscle count density ratios. To ascertain the feasibility of 68Ga-GP in tumor imaging in large animals, PET/CT imaging of 68Ga-GP and 18F-FDG were conducted in New Zealand white rabbits bearing VX2 tumors. Standard uptake value of tumors were determined by PET up to 45 min. To determine blood clearance and half-life of 68Ga-GP, blood samples were collected from 10 seconds to 20 min. Results. Radiochemical purity of 68Ga-GP determined by instant thin-layer chromatography was >95%. Tumor uptake values (SUV for 68Ga-GP and 18F-FDG in New Zealand white rabbits bearing VX2 tumors were 3.25 versus 7.04. PET images in tumor-bearing rats and rabbits confirmed that 68Ga-GP could assess tumor uptake. From blood clearance curve, the half-life of 68Ga-GP was 1.84 hr. Conclusion Our data indicate that it is feasible to use 68Ga-GP to assess tumor angiogenesis.

  4. Elicited Imitation for Brazilian Portuguese

    Directory of Open Access Journals (Sweden)

    Lonsdale, Deryle W.

    2015-01-01

    Full Text Available Elicited imitation (EI is an approach to measuring oral proficiency that consists of having test takers hear a sentence and repeat the sentence exactly as they heard it. Though indirect in nature, EI has successfully shown to correlate with previously established oral proficiency examinations, such as the Oral Proficiency Interview (OPI (Lonsdale and Christensen 2014, Matsushita and Lonsdale 2014, Millard 2011, Thompson 2013. This paper discusses the development, administration, and evaluation of an EI test for the Brazilian Portuguese language. We first discuss the relevant background of oral proficiency examination and EI. After presenting the pertinent research questions, we explain the methodology used to develop the EI test, recruit participants, and administer the test. We present the results and analysis and then summarize the findings, limitations, and possible future work

  5. Novel polyfucosylated N-linked glycopeptides with blood group A, H, X and Y determinants from human small intestinal epithelial cells

    NARCIS (Netherlands)

    Vliegenthart, J.F.G.; Finne, J.; Breimer, M.E.; Hansson, G.C.; Karlsson, K.-A.; Leffler, H.; Halbeek, H. van

    1989-01-01

    A novel type of N-linked glycopeptides representing a major part of the glycans in human small intestinal epithelial cells from blood group A and O individuals were isolated by gel filtrations and affinity chromatography on concanavalin A-Sepharose and Bandeiraea simplicifolia lectin I-Sepharose.

  6. Ultra-high performance liquid chromatography tandem mass spectrometry for the determination of five glycopeptide antibiotics in food and biological samples using solid-phase extraction.

    Science.gov (United States)

    Deng, Fenfang; Yu, Hong; Pan, Xinhong; Hu, Guoyuan; Wang, Qiqin; Peng, Rongfei; Tan, Lei; Yang, Zhicong

    2018-02-23

    This paper demonstrated the development and validation of an ultra-high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) method for simultaneous determination of five glycopeptide antibiotics in food and biological samples. The target glycopeptide antibiotics were isolated from the samples by solvent extraction, and the extracts were cleaned with a tandem solid-phase extraction step using mixed strong cation exchange and hydrophilic/lipophilic balance cartridges. Subsequently, the analytes were eluted with different solvents, and then quantified by UHPLC-MS/MS in the positive ionization mode with multiple reaction monitoring. Under optimal conditions, good linear correlations were obtained for the five glycopeptide antibiotics in the concentration range of 1.0 μg/L to 20.0 μg/L, and with linear correlation coefficients >0.998. Employing this method, the target glycopeptide antibiotics in food and biological samples were identified with a recovery of 83.0-102%, and a low quantitation limit of 1.0 μg/kg in food and 2.0 μg/L in biological samples with low matrix effects. Copyright © 2018 Elsevier B.V. All rights reserved.

  7. Diverse IgG serum response to novel glycopeptide epitopes detected within immunodominant stretches of Epstein-Barr virus glycoprotein 350/220

    DEFF Research Database (Denmark)

    D'Arrigo, Isotta; Cló, Emiliano; Bergström, Tomas

    2013-01-01

    /220 and demonstrate a remarkable variability between individual samples with respect to their reactivity patterns to peptides and glycopeptides. The study provides additional insights into the complex B-cell response towards the EBV gp350/220 envelope protein, which may have implications for diagnostic and vaccine...

  8. Glycopeptides versus β-lactams for the prevention of surgical site infections in cardiovascular and orthopedic surgery: a meta-analysis.

    Science.gov (United States)

    Saleh, Anas; Khanna, Ashish; Chagin, Kevin M; Klika, Alison K; Johnston, Douglas; Barsoum, Wael K

    2015-01-01

    To compare the efficacy of glycopeptides and β-lactams in preventing surgical site infections (SSIs) in cardiac, vascular, and orthopedic surgery. The cost-effectiveness of switching from β-lactams to glycopeptides for preoperative antibiotic prophylaxis has been controversial. β-Lactams are generally recommended in clean surgical procedures, but they are ineffective against resistant gram-positive bacteria. PubMed, International Pharmaceuticals Abstracts, Scopus, and Cochrane were searched for randomized clinical trials comparing glycopeptides and β-lactams for prophylaxis in adults undergoing cardiac, vascular, or orthopedic surgery. Abstracts and conference proceedings were included. Two independent reviewers performed study selection, data extraction, and assessment of risk of bias. Fourteen studies with a total of 8952 patients were analyzed. No difference was detected in overall SSIs between antibiotic types. However, compared with β-lactams, glycopeptides reduced the risk of resistant staphylococcal SSIs by 48% (relative risk, 0.52; 95% confidence interval, 0.29-0.93; P = 0.03) and enterococcal SSIs by 64% (relative risk, 0.36; 95% confidence interval, 0.16-0.80; P = 0.01), but increased respiratory tract infections by 54% (relative risk, 1.54; 95% confidence interval, 1.19-2.01; P ≤ 0.01). Subgroup analysis of cardiac procedures showed superiority of β-lactams in preventing superficial and deep chest SSIs, susceptible staphylococcal SSIs, and respiratory tract infections. Glycopeptides reduce the risk of resistant staphylococcal SSIs and enterococcal SSIs, but increase the risk of respiratory tract infections. Additional high-quality randomized clinical trials are needed as these results are limited by high risk of bias.

  9. Facile and easily popularized synthesis of L-cysteine-functionalized magnetic nanoparticles based on one-step functionalization for highly efficient enrichment of glycopeptides.

    Science.gov (United States)

    Feng, Xiaoyan; Deng, Chunhui; Gao, Mingxia; Zhang, Xiangmin

    2018-01-01

    Protein glycosylation is one of the most important post-translational modifications. Also, efficient enrichment and separation of glycopeptides from complex samples are crucial for the thorough analysis of glycosylation. Developing novel hydrophilic materials with facile and easily popularized synthesis is an urgent need in large-scale glycoproteomics research. Herein, for the first time, a one-step functionalization strategy based on metal-organic coordination was proposed and Fe 3 O 4 nanoparticles were directly functionalized with zwitterionic hydrophilic L-cysteine (L-Cys), greatly simplifying the synthetic procedure. The easily synthesized Fe 3 O 4 /L-Cys possessed excellent hydrophilicity and brief composition, contributing to affinity for glycopeptides and reduction in nonspecific interaction. Thus, Fe 3 O 4 /L-Cys nanoparticles showed outstanding sensitivity (25 amol/μL), high selectivity (mixture of bovine serum albumin and horseradish peroxidase tryptic digests at a mass ratio of 100:1), good reusability (five repeated times), and stability (room temperature storage of 1 month). Encouragingly, in the glycosylation analysis of human serum, a total of 376 glycopeptides with 393 N-glycosylation sites corresponding to 118 glycoproteins were identified after enrichment with Fe 3 O 4 /L-Cys, which was superior to ever reported L-Cys modified magnetic materials. Furthermore, applying the one-step functionalization strategy, cysteamine and glutathione respectively direct-functionalized Fe 3 O 4 nanoparticles were successfully synthesized and also achieved efficient glycopeptide enrichment in human serum. The results indicated that we have presented an efficient and easily popularized strategy in glycoproteomics as well as in the synthesis of novel materials. Graphical abstract Fe 3 O 4 /L-Cys nanoparticles based on one-step functionalization for highly efficient enrichment of glycopeptides.

  10. Needs Elicitation for Novel Pervasive Healthcare Technology

    DEFF Research Database (Denmark)

    Thorpe, Julia Rosemary; Forchhammer, B. H.; Maier, Anja

    2016-01-01

    for pervasive healthcare technology, in which established methods for engaging users to elicit their needs can be difficult or even impossible to apply. In this paper we document our needs elicitation process in a relevant example as a method story, and present our findings and reflections on this as the key...

  11. Requirements Elicitation Problems: A Literature Analysis

    Directory of Open Access Journals (Sweden)

    Bill Davey

    2015-06-01

    Full Text Available Requirements elicitation is the process through which analysts determine the software requirements of stakeholders. Requirements elicitation is seldom well done, and an inaccurate or incomplete understanding of user requirements has led to the downfall of many software projects. This paper proposes a classification of problem types that occur in requirements elicitation. The classification has been derived from a literature analysis. Papers reporting on techniques for improving requirements elicitation practice were examined for the problem the technique was designed to address. In each classification the most recent or prominent techniques for ameliorating the problems are presented. The classification allows the requirements engineer to be sensitive to problems as they arise and the educator to structure delivery of requirements elicitation training.

  12. High-performance liquid chromatographic enantioseparation of monoterpene-based 2-amino carboxylic acids on macrocyclic glycopeptide-based phases.

    Science.gov (United States)

    Sipos, László; Ilisz, István; Pataj, Zoltán; Szakonyi, Zsolt; Fülöp, Ferenc; Armstrong, Daniel W; Péter, Antal

    2010-10-29

    The enantiomers of five monoterpene-based 2-amino carboxylic acids were directly separated on chiral stationary phases containing macrocyclic glycopeptide antibiotics such as teicoplanin (Astec Chirobiotic T and T2) and teicoplanin aglycone (Chirobiotic TAG) as chiral selectors. The effects of pH, the mobile phase composition, the structure of the analyte and temperature on the separations were investigated. Experiments were performed at constant mobile phase compositions in the temperature range 10-40°C to study the effects of temperature and thermodynamic parameters on separations. Apparent thermodynamic parameters and T(iso) values were calculated from plots of ln k or ln α versus 1/T. Some mechanistic aspects of the chiral recognition process are discussed with respect to the structures of the analytes. It was found that the enantioseparations were in most cases enthalpy driven. The sequence of elution of the enantiomers was determined in all cases. Copyright © 2010 Elsevier B.V. All rights reserved.

  13. The Role of IDO in Muc1 Targeted Immunotherapy

    Science.gov (United States)

    2013-01-01

    Besmer*, Teresa L. Tinder , Lopamudra Das Roy, Joseph Lustgarten, Sandra J. Gendler, Pinku Mukherjee Intratumoral Delivery of CpG-Conjugated Anti...3073-87. Epub 2012 Jan 11. PMID: 22238308 3. Mahnaz Sahraei , Lopamudra Das Roy , Jennifer Curry , Teresa Tinder , Sritama Nath , Dahlia M...10.1038/onc.2011.651 4. Dahlia M. Besmer , Dr. Jennifer M. Curry , Dr. Lopamudra D. Roy , Ms. Teresa L. Tinder , Ms. Mahnaz M. Sahraei , Dr

  14. Eliciting Information on Sensitive Matters Without Inviting ...

    Indian Academy of Sciences (India)

    Eliciting Information on Sensitive Matters. Without Inviting Respondents' ... methods based on Randomized Response tech- niques. ... while collecting data on some sensitive issues are well ..... Suppose there is an association of professionals.

  15. Exploring glycopeptide-resistance in Staphylococcus aureus: a combined proteomics and transcriptomics approach for the identification of resistance-related markers

    Directory of Open Access Journals (Sweden)

    Renzoni Adriana

    2006-11-01

    Full Text Available Abstract Background To unravel molecular targets involved in glycopeptide resistance, three isogenic strains of Staphylococcus aureus with different susceptibility levels to vancomycin or teicoplanin were subjected to whole-genome microarray-based transcription and quantitative proteomic profiling. Quantitative proteomics performed on membrane extracts showed exquisite inter-experimental reproducibility permitting the identification and relative quantification of >30% of the predicted S. aureus proteome. Results In the absence of antibiotic selection pressure, comparison of stable resistant and susceptible strains revealed 94 differentially expressed genes and 178 proteins. As expected, only partial correlation was obtained between transcriptomic and proteomic results during stationary-phase. Application of massively parallel methods identified one third of the complete proteome, a majority of which was only predicted based on genome sequencing, but never identified to date. Several over-expressed genes represent previously reported targets, while series of genes and proteins possibly involved in the glycopeptide resistance mechanism were discovered here, including regulators, global regulator attenuator, hyper-mutability factor or hypothetical proteins. Gene expression of these markers was confirmed in a collection of genetically unrelated strains showing altered susceptibility to glycopeptides. Conclusion Our proteome and transcriptome analyses have been performed during stationary-phase of growth on isogenic strains showing susceptibility or intermediate level of resistance against glycopeptides. Altered susceptibility had emerged spontaneously after infection with a sensitive parental strain, thus not selected in vitro. This combined analysis allows the identification of hundreds of proteins considered, so far as hypothetical protein. In addition, this study provides not only a global picture of transcription and expression adaptations

  16. Ecdysteroid-stimulated synthesis and secretion of an N-acetyl-D-glucosamine-rich glycopeptide in a lepidopteran cell line derived from imaginal discs.

    Science.gov (United States)

    Porcheron, P; Morinière, M; Coudouel, N; Oberlander, H

    1991-01-01

    Hormone-regulated processing of N-acetyl-D-glucosamine was studied in an insect cell line derived from imaginal wing discs of the Indian meal moth, Plodia interpunctella (Hübner). The cell line, IAL-PID2, responded to treatment with 20-hydroxyecdysone with increased incorporation of GlcNAc into glycoproteins. Cycloheximide and tunicamycin counteracted the action of the hormone. In particular, treatment with 20-hydroxyecdysone resulted in the secretion of a 5,000 dalton N-acetyl-D-glucosamine-rich glycopeptide by the IAL-PID2 cells. Accumulation of this peptide was prevented by the use of teflubenzuron, a potent chitin synthesis inhibitor. A glycopeptide of similar molecular weight was observed in imaginal discs of P. interpunctella treated with 20-hydroxyecdysone in vitro, under conditions that induce chitin synthesis. Although the function of the 5,000 dalton glycopeptide is not known, we believe that the PID2 cell line is a promising model for molecular analysis of ecdysteroid-regulated processing of aminosugars by epidermal cells during insect development.

  17. Radically altered T cell receptor signaling in glycopeptide-specific T cell hybridoma induced by antigen with minimal differences in the glycan group

    DEFF Research Database (Denmark)

    Jensen, T; Nielsen, M; Gad, Monika

    2001-01-01

    A T cell hybridoma raised against the synthetic glycopeptide T(72)(Tn) was used to study whether the initial TCR signaling events are markedly different when the hybridoma is stimulated with glycopeptides closely related to the cognate glycopeptide antigen. T(72)(Tn) has an alpha-D-GalNAc group O......)(alpha-D-GlcNAc), which differs from T(72)(Tn) solely by the orientation of a hydroxy group in the carbohydrate structure, completely failed to induce detectable tyrosine phosphorylation and IL-2 secretion. APC pulsed with S(72)(Tn), which differs from T(72)(Tn) by not having a methyl group in the serine......-linked to the central threonine in the decapeptide VITAFTEGLK, and the hybridoma is known to be highly specific for this carbohydrate group. T(72)(Tn)-pulsed APC induced tyrosine phosphorylation of the TCR-zeta 21- and 23-kDa proteins and the downstream p42/44 MAP kinase and strong IL-2 secretion. APC pulsed with T(72...

  18. Increasing the productivity of glycopeptides analysis by using higher-energy collision dissociation-accurate mass-product-dependent electron transfer dissociation.

    Science.gov (United States)

    Saba, Julian; Dutta, Sucharita; Hemenway, Eric; Viner, Rosa

    2012-01-01

    Currently, glycans are attracting attention from the scientific community as potential biomarkers or as posttranslational modifications (PTMs) of therapeutic proteins. However, structural characterization of glycoproteins and glycopeptides remains analytically challenging. Here, we report on the implementation of a novel acquisition strategy termed higher-energy collision dissociation-accurate mass-product-dependent electron transfer dissociation (HCD-PD-ETD) on a hybrid linear ion trap-orbitrap mass spectrometer. This acquisition strategy uses the complementary fragmentations of ETD and HCD for glycopeptides analysis in an intelligent fashion. Furthermore, the approach minimizes user input for optimizing instrumental parameters and enables straightforward detection of glycopeptides. ETD spectra are only acquired when glycan oxonium ions from MS/MS HCD are detected. The advantage of this approach is that it streamlines data analysis and improves dynamic range and duty cycle. Here, we present the benefits of HCD-PD-ETD relative to the traditional alternating HCD/ETD for a trainer set containing twelve-protein mixture with two glycoproteins: human serotransferrin, ovalbumin and contaminations of two other: bovine alpha 1 acid glycoprotein (bAGP) and bovine fetuin.

  19. Synthesis of hydrazide-functionalized hydrophilic polymer hybrid graphene oxide for highly efficient N-glycopeptide enrichment and identification by mass spectrometry.

    Science.gov (United States)

    Bai, Haihong; Pan, Yiting; Guo, Cong; Zhao, Xinyuan; Shen, Bingquan; Wang, Xinghe; Liu, Zeyuan; Cheng, Yuanguo; Qin, Weijie; Qian, Xiaohong

    2017-08-15

    Protein N-glycosylation is one of the most important post-translational modifications, participating in many key biological and pathological processes. Large-scale and precise identification of N-glycosylated proteins and peptides is especially beneficial for understanding their biological functions and for discovery of new clinical biomarkers and therapeutic drug targets. However, protein N-glycosylation is microheterogeneous and low abundant in living organisms, therefore specific enrichment of N-glycosylated proteins/peptides before mass spectrometry analysis is a prerequisite. In this work, we developed a new type of polymer hybrid graphene oxide (GO) by in situ growth of hydrazide-functionalized hydrophilic polymer chains on the GO surface (GO-PAAH) for selective N-glycopeptide enrichment and identification by mass spectrometry. The densely attached and low steric hindrance hydrazide groups as well as the highly hydrophilic nature of GO-PAAH facilitate N-glycopeptide enrichment by the combination of hydrazide capturing and HILIC interaction. Taking advantage of the unique features of GO-PAAH, all of the three N-glycopeptides of bovine fetuin were successfully enriched and identified with significantly enhanced signal intensities from a digest mixture of bovine fetuin and bovine serum albumin at a mass ratio of 1:100, demonstrating the excellent enrichment selectivity of GO-PAAH. Furthermore, a total of 507 N-glycosylation sites and 480 N-glycopeptides in 232 N-glycoproteins were enriched and identified from 10μL of human serum by three replicates using this novel enrichment material, which is nearly two times higher than the commercial hydrazide resin based method (280 N-glycosylation sites, 261 N-glycopeptides and 144 N-glycoproteins in three experiments). Among the identified, 95 N-glycosylation sites were not reported in the Uniprot database, and 106 N-glycoproteins were disease related in the Nextprot database, indicating the potential of this new

  20. Responsibilities in the Usability Requirements Elicitation Process

    Directory of Open Access Journals (Sweden)

    Marianella Aveledo

    2008-12-01

    Full Text Available Like any other software system quality attribute, usability places requirements on software components. In particular, it has been demonstrated that certain usability features have a direct impact throughout the software process. This paper details an approach that looks at how to deal with certain usability features in the early software development stages. In particular, we consider usability features as functional usability requirements using patterns that have been termed usability patterns to elicit requirements. Additionally, we clearly establish the responsibilities of all the players at the usability requirements elicitation stage.

  1. Timing of Initiating Glycopeptide Therapy for Methicillin-Resistant Staphylococcus aureus Bacteremia: The Impact on Clinical Outcome

    Directory of Open Access Journals (Sweden)

    Chen-Hsiang Lee

    2013-01-01

    Full Text Available When a Staphylococcus-like organism (SLO is microscopically found in Gram staining of blood culture (BC specimen, it seems reasonable to administrate a glycopeptide (GP for empirical therapy. The paper investigates the risk factors for 14-day mortality in patients with methicillin-resistance Staphylococcus aureus bacteremia (MRSAB and clarifies the impact of the timing for initiating GP therapy. A retrospective study identifies patients with MRSAB (endocarditis was excluded between 2006 and 2009. Patients were categorized as receiving GP at the interval before a preliminary BC report indicating the growth of SLO and the onward 24 hours or receiving GP 24 h after a preliminary BC report indicating the growth of SLO. Total 339 patients were enrolled. There was no difference on the 14-day overall or infection-related mortality rates at the time to administer GP. Multivariate analysis disclosed pneumonia (OR = 4.47; of 95% CI; of 2.09–9.58; and high APACHE II score (OR, 2.81, with 95% CI, 1.19–6.65; were independent risk factors for infection-related mortality. The mortality rate did not decrease following administrating GP immediately after a preliminary BC indicating SLO growth. An additional research for the optimal timing for initiating GP treatment is warranted.

  2. The ABC transporter Tba of Amycolatopsis balhimycina is required for efficient export of the glycopeptide antibiotic balhimycin.

    Science.gov (United States)

    Menges, R; Muth, G; Wohlleben, W; Stegmann, E

    2007-11-01

    All known gene clusters for glycopeptide antibiotic biosynthesis contain a conserved gene supposed to encode an ABC-transporter. In the balhimycin-producer Amycolatopsis balhimycina this gene (tba) is localised between the prephenate dehydrogenase gene pdh and the peptide synthetase gene bpsA. Inactivation of tba in A. balhimycina by gene replacement did not interfere with growth and did not affect balhimycin resistance. However, in the supernatant of the tba mutant RM43 less balhimycin was accumulated compared to the wild type; and the intra-cellular balhimycin concentration was ten times higher in the tba mutant RM43 than in the wild type. These data suggest that the ABC transporter encoded in the balhimycin biosynthesis gene cluster is not involved in resistance but is required for the efficient export of the antibiotic. To elucidate the activity of Tba it was heterologously expressed in Escherichia coli with an N-terminal His-tag and purified by nickel chromatography. A photometric assay revealed that His(6)-Tba solubilised in dodecylmaltoside possesses ATPase activity, characteristic for ABC-transporters.

  3. Eliciting illegal migration rates through list randomization

    NARCIS (Netherlands)

    McKenzie, D.; Siegel, M.

    2013-01-01

    Most migration surveys do not ask about the legal status of migrants due to concerns about the sensitivity of this question. List randomization is a technique that has been used in a number of other social science applications to elicit sensitive information. We trial this technique by adding it to

  4. Eliciting User Requirements Using Appreciative Inquiry

    Science.gov (United States)

    Gonzales, Carol Kernitzki

    2010-01-01

    Many software development projects fail because they do not meet the needs of users, are over-budget, and abandoned. To address this problem, the user requirements elicitation process was modified based on principles of Appreciative Inquiry. Appreciative Inquiry, commonly used in organizational development, aims to build organizations, processes,…

  5. Eliciting Subjective Probabilities with Binary Lotteries

    DEFF Research Database (Denmark)

    Harrison, Glenn W.; Martínez-Correa, Jimmy; Swarthout, J. Todd

    objective probabilities. Drawing a sample from the same subject population, we find evidence that the binary lottery procedure induces linear utility in a subjective probability elicitation task using the Quadratic Scoring Rule. We also show that the binary lottery procedure can induce direct revelation...

  6. A comparison of five elicitation techniques for elicitation of attributes of low involvement products

    DEFF Research Database (Denmark)

    Bech-Larsen, Tino; Nielsen, Niels Asger

    1999-01-01

    of dimensions directed from theories of consumer buying behaviour. Although a number of differences between the techniques are identified in the study, the main findings are that the robustness of the different techniques for attribute elicitation is considerable Udgivelsesdato: JUN......The critical first step for most instruments used in analysing consumer choice and motivation is the identification of product attributes which are important to the consumer and for which there are differences among the available product alternatives. A number of techniques, ranging from...... the complex elicitation of idiosyncratic attributes or simpler picking procedures, has been developed to elicitate such attributes. The purpose of the study presented here is to com-pare attributes of a low involvement product, viz. vegetable oil, elicited by five different techniques on a number...

  7. Eliciting nicotine craving with virtual smoking cues.

    Science.gov (United States)

    Gamito, Pedro; Oliveira, Jorge; Baptista, André; Morais, Diogo; Lopes, Paulo; Rosa, Pedro; Santos, Nuno; Brito, Rodrigo

    2014-08-01

    Craving is a strong desire to consume that emerges in every case of substance addiction. Previous studies have shown that eliciting craving with an exposure cues protocol can be a useful option for the treatment of nicotine dependence. Thus, the main goal of this study was to develop a virtual platform in order to induce craving in smokers. Fifty-five undergraduate students were randomly assigned to two different virtual environments: high arousal contextual cues and low arousal contextual cues scenarios (17 smokers with low nicotine dependency were excluded). An eye-tracker system was used to evaluate attention toward these cues. Eye fixation on smoking-related cues differed between smokers and nonsmokers, indicating that smokers focused more often on smoking-related cues than nonsmokers. Self-reports of craving are in agreement with these results and suggest a significant increase in craving after exposure to smoking cues. In sum, these data support the use of virtual environments for eliciting craving.

  8. An integrated sample pretreatment platform for quantitative N-glycoproteome analysis with combination of on-line glycopeptide enrichment, deglycosylation and dimethyl labeling

    Energy Technology Data Exchange (ETDEWEB)

    Weng, Yejing; Qu, Yanyan; Jiang, Hao; Wu, Qi [National Chromatographic Research and Analysis Center, Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023 (China); University of the Chinese Academy of Sciences, Beijing 100039 (China); Zhang, Lihua, E-mail: lihuazhang@dicp.ac.cn [National Chromatographic Research and Analysis Center, Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023 (China); Yuan, Huiming [National Chromatographic Research and Analysis Center, Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023 (China); Zhou, Yuan [National Chromatographic Research and Analysis Center, Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023 (China); University of the Chinese Academy of Sciences, Beijing 100039 (China); Zhang, Xiaodan; Zhang, Yukui [National Chromatographic Research and Analysis Center, Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023 (China)

    2014-06-23

    Highlights: • An integrated platform for quantitative N-glycoproteome analysis was established. • On-line enrichment, deglycosylation and labeling could be achieved within 160 min. • A N{sub 2}-assisted interface was applied to improve the compatibility of the platform. • The platform exhibited improved quantification accuracy, precision and throughput. - Abstract: Relative quantification of N-glycoproteomes shows great promise for the discovery of candidate biomarkers and therapeutic targets. The traditional protocol for quantitative analysis of glycoproteomes is usually off-line performed, and suffers from long sample preparation time, and the risk of sample loss or contamination due to manual manipulation. In this study, a novel integrated sample preparation platform for quantitative N-glycoproteome analysis was established, with combination of online N-glycopeptide capture by a HILIC column, sample buffer exchange by a N{sub 2}-assisted HILIC–RPLC interface, deglycosylation by a hydrophilic PNGase F immobilized enzymatic reactor (hIMER) and solid dimethyl labeling on a C18 precolumn. To evaluate the performance of such a platform, two equal aliquots of immunoglobulin G (IgG) digests were sequentially pretreated, followed by MALDI-TOF MS analysis. The signal intensity ratio of heavy/light (H/L) labeled deglycosylated peptides with the equal aliquots was 1.00 (RSD = 6.2%, n = 3), much better than those obtained by the offline protocol, with H/L ratio as 0.76 (RSD = 11.6%, n = 3). Additionally, the total on-line sample preparation time was greatly shortened to 160 min, much faster than that of offline approach (24 h). Furthermore, such an integrated pretreatment platform was successfully applied to analyze the two kinds of hepatocarcinoma ascites syngeneic cell lines with high (Hca-F) and low (Hca-P) lymph node metastasis rates. For H/L labeled Hca-P lysates with the equal aliquots, 99.6% of log 2 ratios (H/L) of quantified glycopeptides ranged from −1

  9. High-performance liquid chromatographic enantioseparation of 2-aminomono- and dihydroxycyclopentanecarboxylic and 2-aminodihydroxycyclohexanecarboxylic acids on macrocyclic glycopeptide-based phases.

    Science.gov (United States)

    Berkecz, Róbert; Ilisz, István; Benedek, Gabriella; Fülöp, Ferenc; Armstrong, Daniel W; Péter, Antal

    2009-02-06

    The direct separation of the enantiomers of four 2-aminomono- or dihydroxycyclopentanecarboxylic acids and four 2-aminodihydroxycyclohexanecarboxylic acids was performed on chiral stationary phases containing macrocyclic glycopeptide antibiotics such as teicoplanin (Astec Chirobiotic T and T2), teicoplanin aglycone (Chirobiotic TAG) or ristocetin A (Chirobiotic R) as chiral selectors. The effects of the nature of organic modifiers, the pH, the mobile phase composition and the structures of the analytes on the separation were investigated. Chirobiotic TAG, and in some cases Chirobiotic T, proved to be the most useful of these columns. The elution sequence was determined in most cases.

  10. Eliciting Perceptual Ground Truth for Image Segmentation

    OpenAIRE

    Hodge, Victoria Jane; Eakins, John; Austin, Jim

    2006-01-01

    In this paper, we investigate human visual perception and establish a body of ground truth data elicited from human visual studies. We aim to build on the formative work of Ren, Eakins and Briggs who produced an initial ground truth database. Human subjects were asked to draw and rank their perceptions of the parts of a series of figurative images. These rankings were then used to score the perceptions, identify the preferred human breakdowns and thus allow us to induce perceptual rules for h...

  11. The lectin domains of polypeptide GalNAc-transferases exhibit carbohydrate-binding specificity for GalNAc: lectin binding to GalNAc-glycopeptide substrates is required for high density GalNAc-O-glycosylation

    DEFF Research Database (Denmark)

    Wandall, Hans H; Irazoqui, Fernando; Tarp, Mads Agervig

    2007-01-01

    Initiation of mucin-type O-glycosylation is controlled by a large family of UDP GalNAc:polypeptide N-acetylgalactosaminyltransferases (GalNAc-transferases). Most GalNAc-transferases contain a ricin-like lectin domain in the C-terminal end, which may confer GalNAc-glycopeptide substrate specificit...

  12. Mucin-type O-glycosylation is controlled by short- and long-range glycopeptide substrate recognition that varies among members of the polypeptide GalNAc transferase family

    DEFF Research Database (Denmark)

    Revoredo, Leslie; Wang, Shengjun; Bennett, Eric Paul

    2016-01-01

    A large family of UDP-GalNAc:polypeptide GalNAc transferases (ppGalNAc-Ts) initiates and defines sites of mucin-type Ser/Thr-O-GalNAc glycosylation. Family members have been classified into peptide- and glycopeptide-preferring subfamilies, although both families possess variable activities agains...

  13. Earthquakes and Tectonics Expert Judgment Elicitation Project

    International Nuclear Information System (INIS)

    Coppersmith, K.J.; Perman, R.C.; Youngs, R.R.

    1993-02-01

    This report summarizes the results of the Earthquakes and Tectonics Expert Judgement Excitation Project sponsored by the Electric Power Research Institute (EPRI). The objectives of this study were two-fold: (1) to demonstrate methods for the excitation of expert judgement, and (2) to quantify the uncertainties associated with earthquake and tectonics issues for use in the EPRI-HLW performance assessment. Specifically, the technical issue considered is the probability of differential fault displacement through the proposed repository at Yucca Mountain, Nevada. For this study, a strategy for quantifying uncertainties was developed that relies on the judgements of multiple experts. A panel of seven geologists and seismologists was assembled to quantify the uncertainties associated with earthquake and tectonics issues for the performance assessment model. A series of technical workshops focusing on these issues were conducted. Finally, each expert was individually interviewed in order to elicit his judgement regarding the technical issues and to provide the technical basis for his assessment. This report summarizes the methodologies used to elicit the judgements of the earthquakes and tectonics experts (termed ''specialists''), and summarizes the technical assessments made by the expert panel

  14. Cellular requirements for cutaneous sensitivity elicitation.

    Science.gov (United States)

    Aoki, I

    1985-01-01

    The role of glass-adherent cells in cutaneous sensitivity (CS) elicitation has been analyzed in this study. CS responses have been revealed to be mediated by at least two distinct subsets of genetically restricted T cells: I-restricted 'DTH-like' T cells and K/D-restricted 'CTL-like' T cells. Both T-cell responses require I-A-positive glass-adherent cell populations, which lack T-cell markers, to manifest their activities. The role of the adherent cells is different in the 'DTH-like' responses and the 'CTL-like' responses. The disparities between the present results and previous contentions are discussed in this paper.

  15. Eliciting promises from children reduces cheating.

    Science.gov (United States)

    Heyman, Gail D; Fu, Genyue; Lin, Jianyan; Qian, Miao K; Lee, Kang

    2015-11-01

    Widespread cheating can undermine rules that are necessary for maintaining social order. Preventing cheating can be a challenge, especially with regard to children, who as a result of their limited executive function skills may have particular difficulty with resisting temptation to cheat. We examined one approach designed to help children resist this temptation: eliciting a verbal commitment to not cheat. We tested 4- to 7-year-olds (total N = 330) and found that starting at 5 years of age, a verbal commitment to not cheat led to a substantial reduction in cheating. The results suggest that verbal commitments can be used to help children overcome temptations and comply with rules. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. Eliciting consumer preferences for health plans.

    Science.gov (United States)

    Booske, B C; Sainfort, F; Hundt, A S

    1999-10-01

    To examine (1) what people say is important to them in choosing a health plan; (2) the effect, if any, that giving health plan information has on what people say is important to them; and (3) the effect of preference elicitation methods on what people say is important. A random sample of 201 Wisconsin state employees who participated in a health plan choice experiment during the 1995 open enrollment period. We designed a computer system to guide subjects through the review of information about health plan options. The system began by eliciting the stated preferences of the subjects before they viewed the information, at time 0. Subjects were given an opportunity to revise their preference structures first after viewing summary information about four health plans (time 1) and then after viewing more extensive, detailed information about the same options (time 2). At time 2, these individuals were also asked to rate the relative importance of a predefined list of health plan features presented to them. Data were collected on the number of attributes listed at each point in time and the importance weightings assigned to each attribute. In addition, each item on the attribute list was content analyzed. The provision of information changes the preference structures of individuals. Costs (price) and coverage dominated the attributes cited both before and after looking at health plan information. When presented with information on costs, quality, and how plans work, many of these relatively well educated consumers revised their preference structures; yet coverage and costs remained the primary cited attributes. Although efforts to provide health plan information should continue, decisions on the information to provide and on making it available are not enough. Individuals need help in understanding, processing, and using the information to construct their preferences and make better decisions.

  17. High-performance liquid chromatographic enantioseparation of unusual isoxazoline-fused 2-aminocyclopentanecarboxylic acids on macrocyclic glycopeptide-based chiral stationary phases.

    Science.gov (United States)

    Sipos, László; Ilisz, István; Nonn, Melinda; Fülöp, Ferenc; Pataj, Zoltán; Armstrong, Daniel W; Péter, Antal

    2012-04-06

    The enantiomers of four unusual isoxazoline-fused 2-aminocyclopentanecarboxylic acids were directly separated on chiral stationary phases containing macrocyclic glycopeptide antibiotics teicoplanin (Astec Chirobiotic T and T2), teicoplanin aglycone (Chirobiotic TAG), vancomycin (Chirobiotic V) and vancomycin aglycone (Chirobiotic VAG) as chiral selectors. The effects of the mobile phase composition, the structure of the analytes and temperature on the separations were investigated. Experiments were performed at constant mobile phase compositions in the temperature range 5-45 °C to study the effects of temperature, and thermodynamic parameters were calculated from plots of lnk or lnα versus 1/T. Some mechanistic aspects of the chiral recognition process are discussed with respect to the structures of the analytes. It was found that the enantiomeric separations were in most cases enthalpy-driven. The sequence of elution of the enantiomers was determined in all cases. Copyright © 2011 Elsevier B.V. All rights reserved.

  18. A SYSTEMATIC LITERATURE REVIEW ABOUT SOFTWARE REQUIREMENTS ELICITATION

    Directory of Open Access Journals (Sweden)

    LENIS R. WONG

    2017-02-01

    Full Text Available Requirements Elicitation is recognized as one of the most important activity in software development process as it has direct impact on its success. Although there are many proposals for improving this task, still there are issues which have to be solved. This paper aims to identify the current status of the latest researches related to software requirements elicitation through general framework for literature review, in order to answer the following research questions: Q1 What aspects have been covered by different proposal of requirements elicitation? Q2 What activities of the requirements elicitation process have been covered? And Q3 What factors influence on requirements elicitation and how? A cross-analysis of the outcome was performed. One of the results showed that requirements elicitation process needs improvements.

  19. Acting green elicits a literal warm glow

    Science.gov (United States)

    Taufik, Danny; Bolderdijk, Jan Willem; Steg, Linda

    2015-01-01

    Environmental policies are often based on the assumption that people only act environmentally friendly if some extrinsic reward is implicated, usually money. We argue that people might also be motivated by intrinsic rewards: doing the right thing (such as acting environmentally friendly) elicits psychological rewards in the form of positive feelings, a phenomenon known as warm glow. Given the fact that people's psychological state may affect their thermal state, we expected that this warm glow could express itself quite literally: people who act environmentally friendly may perceive the temperature to be higher. In two studies, we found that people who learned they acted environmentally friendly perceived a higher temperature than people who learned they acted environmentally unfriendly. The underlying psychological mechanism pertains to the self-concept: learning you acted environmentally friendly signals to yourself that you are a good person. Together, our studies show that acting environmentally friendly can be psychologically rewarding, suggesting that appealing to intrinsic rewards can be an alternative way to encourage pro-environmental actions.

  20. A method to elicit beliefs as most likely intervals

    NARCIS (Netherlands)

    Schlag, K.H.; van der Weele, J.J.

    2015-01-01

    We show how to elicit the beliefs of an expert in the form of a "most likely interval", a set of future outcomes that are deemed more likely than any other outcome. Our method, called the Most Likely Interval elicitation rule (MLI), asks the expert for an interval and pays according to how well the

  1. The potential for using visual elicitation in understanding preschool ...

    African Journals Online (AJOL)

    We explore the use of video and photo elicitation in a research study undertaken to understand the way in which preschool teachers perceive and construct their provision of children's educational experiences. We explore the value of visually elicited interviews based on video footage and photographs captured during ...

  2. Preparation of hydrophilic monolithic capillary column by in situ photo-polymerization of N-vinyl-2-pyrrolidinone and acrylamide for highly selective and sensitive enrichment of N-linked glycopeptides.

    Science.gov (United States)

    Jiang, Hao; Yuan, Huiming; Qu, Yanyan; Liang, Yu; Jiang, Bo; Wu, Qi; Deng, Nan; Liang, Zhen; Zhang, Lihua; Zhang, Yukui

    2016-01-01

    In this study, a novel kind of amide functionalized hydrophilic monolith was synthesized by the in situ photo-polymerization of N-vinyl-2-pyrrolidinone (NVP), acrylamide (AM), and N, N'-methylenebisacrylamide (MBA) in a UV transparent capillary, and successfully applied for hydrophilic interaction chromatography (HILIC) based enrichment of N-linked glycopeptides. With 2 μg of the tryptic digests of IgG as the sample, after enrichment, 18 glycopeptides could be identified by MALDI-TOF/TOF MS analysis. Furthermore, with the mixture of BSA and IgG digests (10,000:1, m/m) as the sample, 6 N-linked glycopeptides were unambiguously identified after enrichment, indicating the high selectivity and good specificity of such material. Moreover, such a monolithic capillary column was also applied for the N-glycosylation sites profiling of 6 μg protein digests from HeLa cells and 1 μL human serum. In total, 530 and 262 unique N-glycosylated peptides were identified, respectively, corresponding to 282 and 124N-glycoproteins, demonstrating its great potential for the large scale glycoproteomics analysis. Copyright © 2015 Elsevier B.V. All rights reserved.

  3. PABRE-Proj: applying patterns in requirements elicitation

    OpenAIRE

    Palomares Bonache, Cristina; Quer Bosor, Maria Carme; Franch Gutiérrez, Javier

    2013-01-01

    Software requirement patterns have been proposed as a type of artifact for fostering requirements reuse. In this paper, we present PABRE-Proj, a tool aimed at supporting requirements elicitation and specification. Peer Reviewed

  4. The Interview as an Approach to Elicit Requirements

    Directory of Open Access Journals (Sweden)

    Luz Marina Iriarte

    2013-07-01

    Full Text Available In many software projects requirements elicitation is incomplete or inconsistent. One issue that works for this is presented has to be with the requirements engineers use a single method to do it, which can cause a deficiency in the expected results. Among the factors contributing to the success of this stage of the life cycle is an adequate selection of the elicitation technique and other approaches needed. This article describes an experimental study to elicit requirements, in which was applied a combination of methods and techniques, and discusses the advantages of doing it this way. The results obtained allow concluding that to achieve adequate elicitation is necessary to combine several techniques and methods.

  5. Distributed and Collaborative Requirements Elicitation Based on Social Intelligence

    NARCIS (Netherlands)

    Wen, Bin; Luo, Z.; Liang, P.

    2012-01-01

    Requirements is the formal expression of user's needs. Also, requirements elicitation is the process of activity focusing on requirements collection. Traditional acquisition methods, such as interview, observation and prototype, are unsuited for the service-oriented software development featuring in

  6. Film clips and narrative text as subjective emotion elicitation techniques.

    Science.gov (United States)

    Zupan, Barbra; Babbage, Duncan R

    2017-01-01

    Film clips and narrative text are useful techniques in eliciting emotion in a laboratory setting but have not been examined side-by-side using the same methodology. This study examined the self-identification of emotions elicited by film clip and narrative text stimuli to confirm that selected stimuli appropriately target the intended emotions. Seventy participants viewed 30 film clips, and 40 additional participants read 30 narrative texts. Participants identified the emotion experienced (happy, sad, angry, fearful, neutral-six stimuli each). Eighty-five percent of participants self-identified the target emotion for at least two stimuli for all emotion categories of film clips, except angry (only one) and for all categories of narrative text, except fearful (only one). The most effective angry text was correctly identified 74% of the time. Film clips were more effective in eliciting all target emotions in participants for eliciting the correct emotion (angry), intensity rating (happy, sad), or both (fearful).

  7. CCSI Risk Estimation: An Application of Expert Elicitation

    Energy Technology Data Exchange (ETDEWEB)

    Engel, David W.; Dalton, Angela C.

    2012-10-01

    The Carbon Capture Simulation Initiative (CCSI) is a multi-laboratory simulation-driven effort to develop carbon capture technologies with the goal of accelerating commercialization and adoption in the near future. One of the key CCSI technical challenges is representing and quantifying the inherent uncertainty and risks associated with developing, testing, and deploying the technology in simulated and real operational settings. To address this challenge, the CCSI Element 7 team developed a holistic risk analysis and decision-making framework. The purpose of this report is to document the CCSI Element 7 structured systematic expert elicitation to identify additional risk factors. We review the significance of and established approaches to expert elicitation, describe the CCSI risk elicitation plan and implementation strategies, and conclude by discussing the next steps and highlighting the contribution of risk elicitation toward the achievement of the overarching CCSI objectives.

  8. The potential for using visual elicitation in understanding preschool ...

    African Journals Online (AJOL)

    We explore the use of video and photo elicitation in a research study undertaken to ... system, in the District Centres for Early Childhood Education (DICECE), in Kenya. In this paper ..... photographs and even direct to a hand-held computer”.

  9. Expert elicitation and the problem of detecting undeclared activities

    International Nuclear Information System (INIS)

    Pilat, Joseph F.; Sylvester, Kori Budlong; Stanbro, William D.

    2002-01-01

    Measures applicable to the detection of undeclared activities are not well established, and their effectiveness is uncertain. To detect clandestine paths, the IAEA is still developing processes and procedures. As the Agency gains experience with new measures and with integrated safeguards, dealing with such problems may become more experience-based and perhaps more closely parallel the process with current safeguards where detection probabilities for the measures to be utilized on declared paths are well characterized. Whether or not this point will be reached for undeclared and mixed paths, the only tool that appears suitable at present for the purpose of generating a reasonable detection probability that can over time be tested against reality and, if necessary, adjusted is formal expert judgment, or expert elicitation. Formal expert elicitation is a structured process that makes use of people knowledgeable in certain areas to make assessments. To provide a 'proof of principle' of this methodology for presentation to the Agency, experts in nuclear technology, nonproliferation, safeguards and open source information, as well as in formal expert elicitation processes, engaged in three illustrative expert elicitations on assessing information analysis as a means to detect undeclared activities. These elicitations were successful. This paper will discuss the process of and issues raised by the elicitations.

  10. Eliciting expert opinion for economic models: an applied example.

    Science.gov (United States)

    Leal, José; Wordsworth, Sarah; Legood, Rosa; Blair, Edward

    2007-01-01

    Expert opinion is considered as a legitimate source of information for decision-analytic modeling where required data are unavailable. Our objective was to develop a practical computer-based tool for eliciting expert opinion about the shape of the uncertainty distribution around individual model parameters. We first developed a prepilot survey with departmental colleagues to test a number of alternative approaches to eliciting opinions on the shape of the uncertainty distribution around individual parameters. This information was used to develop a survey instrument for an applied clinical example. This involved eliciting opinions from experts to inform a number of parameters involving Bernoulli processes in an economic model evaluating DNA testing for families with a genetic disease, hypertrophic cardiomyopathy. The experts were cardiologists, clinical geneticists, and laboratory scientists working with cardiomyopathy patient populations and DNA testing. Our initial prepilot work suggested that the more complex elicitation techniques advocated in the literature were difficult to use in practice. In contrast, our approach achieved a reasonable response rate (50%), provided logical answers, and was generally rated as easy to use by respondents. The computer software user interface permitted graphical feedback throughout the elicitation process. The distributions obtained were incorporated into the model, enabling the use of probabilistic sensitivity analysis. There is clearly a gap in the literature between theoretical elicitation techniques and tools that can be used in applied decision-analytic models. The results of this methodological study are potentially valuable for other decision analysts deriving expert opinion.

  11. Green Software Engineering Adaption In Requirement Elicitation Process

    Directory of Open Access Journals (Sweden)

    Umma Khatuna Jannat

    2015-08-01

    Full Text Available A recent technology investigates the role of concern in the environment software that is green software system. Now it is widely accepted that the green software can fit all process of software development. It is also suitable for the requirement elicitation process. Now a days software companies have used requirements elicitation techniques in an enormous majority. Because this process plays more and more important roles in software development. At the present time most of the requirements elicitation process is improved by using some techniques and tools. So that the intention of this research suggests to adapt green software engineering for the intention of existing elicitation technique and recommend suitable actions for improvement. This research being involved qualitative data. I used few keywords in my searching procedure then searched IEEE ACM Springer Elsevier Google scholar Scopus and Wiley. Find out articles which published in 2010 until 2016. Finding from the literature review Identify 15 traditional requirement elicitations factors and 23 improvement techniques to convert green engineering. Lastly The paper includes a squat review of the literature a description of the grounded theory and some of the identity issues related finding of the necessity for requirements elicitation improvement techniques.

  12. New chiral and restricted-access materials containing glycopeptides as selectors for the high-performance liquid chromatographic determination of chiral drugs in biological matrices.

    Science.gov (United States)

    Gasparrini, Francesco; Cancelliere, Giovanna; Ciogli, Alessia; D'Acquarica, Ilaria; Misiti, Domenico; Villani, Claudio

    2008-05-16

    Two new chiral and restricted-access materials containing glycopeptide antibiotics as chiral selectors (chiro-Glyco-RAM) were designed, suitable for the direct HPLC injection of biological fluids containing chiral drugs without any sample pre-treatment or pre-columns coupling. The external surface of the porous silica support was covered with a bio-compatible hydrophilic polymeric network (polyvinyl alcohol, PVA) while the chiral phase based on either teicoplanin (TE) or teicoplanin aglycone (TAG) was exclusively confined to the internal region. The chiro-Glyco-RAM supports were synthesized by the following steps: (a) introduction of 3-aminopropyl groups on 100 A pore size silica gel; (b) activation of the aminopropylated silica with 1,6-diisocyanatohexane; (c) functionalization of the external region of the porous silica with PVA; (d) covalent linking of TE/TAG to the internal surface. The average pore diameter of the chiro-Glyco-RAM supports, calculated by inverse size-exclusion chromatography (ISEC), was about 80 A and able to exclude macromolecules heavier than about 20,000 Da (such as the most abundant serum proteins) from the pores. The recovery of bovine serum albumin (BSA) was almost quantitative. HPLC analyses of model chiral drugs were performed using hydro-organic mobile phases consisting of an organic solvent (acetonitrile or methanol) and aqueous solutions of ammonium acetate (0.020 M) or ammonium formate (0.0025-0.0050 M).

  13. MoFi: A Software Tool for Annotating Glycoprotein Mass Spectra by Integrating Hybrid Data from the Intact Protein and Glycopeptide Level.

    Science.gov (United States)

    Skala, Wolfgang; Wohlschlager, Therese; Senn, Stefan; Huber, Gabriel E; Huber, Christian G

    2018-04-18

    Hybrid mass spectrometry (MS) is an emerging technique for characterizing glycoproteins, which typically display pronounced microheterogeneity. Since hybrid MS combines information from different experimental levels, it crucially depends on computational methods. Here, we describe a novel software tool, MoFi, which integrates hybrid MS data to assign glycans and other post-translational modifications (PTMs) in deconvoluted mass spectra of intact proteins. Its two-stage search algorithm first assigns monosaccharide/PTM compositions to each peak and then compiles a hierarchical list of glycan combinations compatible with these compositions. Importantly, the program only includes those combinations which are supported by a glycan library as derived from glycopeptide or released glycan analysis. By applying MoFi to mass spectra of rituximab, ado-trastuzumab emtansine, and recombinant human erythropoietin, we demonstrate how integration of bottom-up data may be used to refine information collected at the intact protein level. Accordingly, our software reveals that a single mass frequently can be explained by a considerable number of glycoforms. Yet, it simultaneously ranks proteoforms according to their probability, based on a score which is calculated from relative glycan abundances. Notably, glycoforms that comprise identical glycans may nevertheless differ in score if those glycans occupy different sites. Hence, MoFi exposes different layers of complexity that are present in the annotation of a glycoprotein mass spectrum.

  14. Time course of brain activation elicited by basic emotions.

    Science.gov (United States)

    Hot, Pascal; Sequeira, Henrique

    2013-11-13

    Whereas facial emotion recognition protocols have shown that each discrete emotion has a specific time course of brain activation, there is no electrophysiological evidence to support these findings for emotional induction by complex pictures. Our objective was to specify the differences between the time courses of brain activation elicited by feelings of happiness and, with unpleasant pictures, by feelings of disgust and sadness. We compared event-related potentials (ERPs) elicited by the watching of high-arousing pictures from the International Affective Picture System, selected to induce specific emotions. In addition to a classical arousal effect on late positive components, we found specific ERP patterns for each emotion in early temporal windows (emotion to be associated with different brain processing after 140 ms, whereas happiness and sadness differed in ERPs elicited at the frontal and central sites after 160 ms. Our findings highlight the limits of the classical averaging of ERPs elicited by different emotions inside the same valence and suggest that each emotion could elicit a specific temporal pattern of brain activation, similar to those observed with emotional face recognition.

  15. Patient Health Goals Elicited During Home Care Admission: A Categorization.

    Science.gov (United States)

    Sockolow, Paulina; Radhakrishnan, Kavita; Chou, Edgar Y; Wojciechowicz, Christine

    2017-11-01

    Home care agencies are initiating "patient health goal elicitation" activities as part of home care admission planning. We categorized elicited goals and identified "clinically informative" goals at a home care agency. We examined patient goals that admitting clinicians documented in the point-of-care electronic health record; conducted content analysis on patient goal data to develop a coding scheme; grouped goal themes into codes; assigned codes to each goal; and identified goals that were in the patient voice. Of the 1,763 patient records, 16% lacked a goal; only 15 goals were in a patient's voice. Nurse and physician experts identified 12 of the 20 codes as clinically important accounting for 82% of goal occurrences. The most frequent goal documented was safety/falls (23%). Training and consistent communication of the intent and operationalization of patient goal elicitation may address the absence of patient voice and the less than universal recording of home care patients' goals.

  16. Improvement of Requirement Elicitation Process through Cognitive Psychology

    Directory of Open Access Journals (Sweden)

    Sana Fatima

    2017-06-01

    Full Text Available Proper requirement elicitation is necessary for client satisfaction along with the overall project success, but requirement engineers face problems in understanding user requirements and the users of the required system fail to make requirement engineering team understand what they actually want. It is then responsibility of requirement engineers to extract proper requirements. This paper discusses how to use cognitive psychology and learning style models (LSM to understand the psychology of clients. Moreover, it also discusses usage of proper elicitation technique according to one’s learning style and gather the right requirements.

  17. Belief elicitation in experiments: Is there a hedging problem?

    DEFF Research Database (Denmark)

    Blanco, Mariana; Engelmann, Dirk; Koch, Alexander

    2010-01-01

    Belief-elicitation experiments usually reward accuracy of stated beliefs in addition to payments for other decisions. But this allows risk-averse subjects to hedge with their stated beliefs against adverse outcomes of the other decisions. So can we trust the existing belief-elicitation results...... opportunities are very prominent. If hedging opportunities are transparent, and incentives to hedge are strong, many subjects do spot hedging opportunities and respond to them. The bias can go beyond players actually hedging themselves, because some expect others to hedge and best respond to this....

  18. The use of high-throughput sequencing to investigate an outbreak of glycopeptide-resistant Enterococcus faecium with a novel quinupristin-dalfopristin resistance mechanism.

    Science.gov (United States)

    Shaw, Timothy D; Fairley, D J; Schneiders, T; Pathiraja, M; Hill, R L R; Werner, G; Elborn, J S; McMullan, R

    2018-02-24

    High-throughput sequencing (HTS) has successfully identified novel resistance genes in enterococci and determined clonal relatedness in outbreak analysis. We report the use of HTS to investigate two concurrent outbreaks of glycopeptide-resistant Enterococcus faecium (GRE) with an uncharacterised resistance mechanism to quinupristin-dalfopristin (QD). Seven QD-resistant and five QD-susceptible GRE isolates from a two-centre outbreak were studied. HTS was performed to identify genes or predicted proteins that were associated with the QD-resistant phenotype. MLST and SNP typing on HTS data was used to determine clonal relatedness. Comparative genomic analysis confirmed this GRE outbreak involved two distinct clones (ST80 and ST192). HTS confirmed the absence of known QD resistance genes, suggesting a novel mechanism was conferring resistance. Genomic analysis identified two significant genetic determinants with explanatory power for the high level of QD resistance in the ST80 QD-resistant clone: an additional 56aa leader sequence at the N-terminus of the lsaE gene and a transposon containing seven genes encoding proteins with possible drug or drug-target modification activities. However, HTS was unable to conclusively determine the QD resistance mechanism and did not reveal any genetic basis for QD resistance in the ST192 clone. This study highlights the usefulness of HTS in deciphering the degree of relatedness in two concurrent GRE outbreaks. Although HTS was able to reveal some genetic candidates for uncharacterised QD resistance, this study demonstrates the limitations of HTS as a tool for identifying putative determinants of resistance to QD.

  19. Application of expert elicitation techniques in human reliability, assessment

    International Nuclear Information System (INIS)

    Sanyasi Rao, V.V.S.; Saraf, R.K.; Ghosh, A.K.; Kushwaha, H.S.

    2006-01-01

    Expert elicitation techniques are being used, in the area of technological forecasting, in estimating data needed for analysis when it is either difficult to arrive at the data by experimental means or when it is quite involved to plan and conduct the experiment. In this study, expert elicitation techniques are applied to the evaluation of the frequencies of the various accident sequences that can result from the initiating event (IE) 'High Pressure Process Water (HPPW) system failure' in typical Indian Pressurised Heavy Water Reactor (IPHWR) of the older generation. The Operating Procedure under Emergency Conditions (OPEC) for this IE involves human actions according to a pre-defined procedure. The Human Error Probabilities for all these human actions are obtained using expert elicitation techniques. These techniques aim at eliciting the opinion of the experts in the area of interest with regard to the issue in question. The uncertainty is analysed by employing the measure of dissonance and the most probable range of human error probabilities are arrived at by maximizing this measure. These values are combined using the same procedures mentioned above to yield a distribution representing the uncertainty associated with the predictions. (author)

  20. Belief elicitation in experiments: is there a hedging problem?

    Czech Academy of Sciences Publication Activity Database

    Blanco, M.; Engelmann, Dirk; Koch, A. K.; Normann, H.-T.

    2010-01-01

    Roč. 13, č. 4 (2010), s. 412-438 ISSN 1386-4157 Institutional research plan: CEZ:AV0Z70850503 Keywords : belief elicitation * hedging * experimental methodology Subject RIV: AH - Economics Impact factor: 1.868, year: 2010

  1. Elicitation support requirements of multi-expertise teams

    NARCIS (Netherlands)

    Bitter-Rijpkema, M.; Martens, R.L.; Jochems, W.M.G.

    2005-01-01

    Tools to support knowledge elicitation are more and more used in situations where employees or students collaborate using the computer. Studies indicate that there exist differences between experts and novices regarding their methods of work and reasoning. However, the commonly preferred approach

  2. Requirements Elicitation in a Telemedicine Pain-treatment Trial

    NARCIS (Netherlands)

    Widya, I.A.; Bults, Richard G.A.; van Beijnum, Bernhard J.F.; Sandsjö, L.; Schaake, L.; Huis in 't Veld, M.H.A.; Jones, Valerie M.; Hermens, Hermanus J.; Ryan, K.; Robinson, W.

    2009-01-01

    This paper presents the early phase requirements elicitation for a work-related neck-shoulder pain teletreatment trial and the assessment of those requirements in respect of their importance to the trial and the feasibility of the needed software adaptations of the telemedicine system within the

  3. Elicitation Support Requirements of Multi-Expertise Teams

    Science.gov (United States)

    Bitter-Rijpkema, Marlies; Martens, Rob; Jochems, Wim

    2005-01-01

    Tools to support knowledge elicitation are used more and more in situations where employees or students collaborate using the computer. Studies indicate that differences exist between experts and novices regarding their methods of work and reasoning. However, the commonly preferred approach tends to deal with team members as a single system with…

  4. Experimental elicitation with hydroxyisohexyl-3-cyclohexene carboxaldehyde-containing deodorants

    DEFF Research Database (Denmark)

    Jørgensen, Pia Haslund; Jensen, Charlotte Devantier; Rastogi, Suresh

    2007-01-01

    Hydroxyisohexyl-3-cyclohexene carboxaldehyde (HICC) known as Lyral is a frequent allergen. It is used in more than 50% of marketed deodorants. The aim of the present study was to determine elicitation thresholds for HICC under simulated conditions of deodorant use. 15 patients with previously...

  5. Do community and autonomy moral violations elicit different emotions?

    Science.gov (United States)

    Kollareth, Dolichan; Kikutani, Mariko; Shirai, Mariko; Russell, James A

    2018-06-11

    According to one important set of theories, different domains of immorality are linked to different discrete emotions-panculturally. Violations against the community elicit contempt, whereas violations against an individual elicit anger. To test this theory, American, Indian and Japanese participants (N = 480) indicated contempt and anger reactions (with verbal rating and face selection) to both the types of immorality. To remedy method problems in previous research, community and autonomy violations were created for the same story-frame, by varying the target to be either the community or an individual. Community and autonomy violations did not differ significantly in the emotion elicited: overall, both types of violations elicited more anger than contempt (and more negative emotion of any kind than positive emotion). By verbal rating, Americans and Indians reported more anger than contempt for both types of violation, whereas Japanese reported more contempt than anger for both types. By face selection, the three cultural groups selected anger more than contempt for both types of violation. The results speak against defining distinct domains of morality by their association with distinct emotions. © 2018 International Union of Psychological Science.

  6. Effect of elicitation on picrotin and picrotoxinin production from in ...

    African Journals Online (AJOL)

    Picrorhiza kurrooa Royel ex. Benth. is an important medicinal plant of Himalayan region and a good source of iridoid glycosides. Picrotin and picrotoxinin are compounds produced by P. kurrooa which are widely used in treatment of hepatic diseases. Elicitation is one of the best effective methods which enhance secondary ...

  7. The Role of Elicited Verbal Imitation in Toddlers' Word Learning

    Science.gov (United States)

    Hodges, Rosemary; Munro, Natalie; Baker, Elise; McGregor, Karla; Docking, Kimberley; Arciuli, Joanne

    2016-01-01

    This study is about the role of elicited verbal imitation in toddler word learning. Forty-eight toddlers were taught eight nonwords linked to referents. During training, they were asked to imitate the nonwords. Naming of the referents was tested at three intervals (one minute later [uncued], five minutes, and 1-7 days later [cued]) and recognition…

  8. Eliciting the Dutch loan phoneme /g/ with the Menu Task

    NARCIS (Netherlands)

    Hamann, S.; de Jonge, A.

    2015-01-01

    This article introduces the menu task, which can be used to elicit infrequent sounds such as loan phonemes that only occur in a restricted set of words. The menu task is similar to the well-known map task and involves the interaction of two participants to create a menu on the basis of a list of

  9. Elicited Production of Relative Clauses in Children with Williams Syndrome

    Science.gov (United States)

    Zukowski, Andrea

    2009-01-01

    Relative clauses have been implicated alternately as a strength and a weakness in the language of people with Williams Syndrome (WS). To clarify the facts, an elicited production test was administered to 10 people with WS (age 10-16 years), 10 typically developing children (age 4-7 years), and 12 typically developing adults. Nearly every WS…

  10. Delphi Fuzzy Elicitation Technique in the Determination of Third ...

    African Journals Online (AJOL)

    The Delphi technique via the expert elicitation method becomes extremely handy particularly in view of limited availability of data in determining failure probabilities of onshore transmission pipelines in the Niger Delta region of Nigeria occasioned by third party activity. Using, ten (10) experts opinion elucidated individually ...

  11. Pattern Visual Evoked Potentials Elicited by Organic Electroluminescence Screen

    Directory of Open Access Journals (Sweden)

    Celso Soiti Matsumoto

    2014-01-01

    Full Text Available Purpose. To determine whether organic electroluminescence (OLED screens can be used as visual stimulators to elicit pattern-reversal visual evoked potentials (p-VEPs. Method. Checkerboard patterns were generated on a conventional cathode-ray tube (S710, Compaq Computer Co., USA screen and on an OLED (17 inches, 320 × 230 mm, PVM-1741, Sony, Tokyo, Japan screen. The time course of the luminance changes of each monitor was measured with a photodiode. The p-VEPs elicited by these two screens were recorded from 15 eyes of 9 healthy volunteers (22.0 ± 0.8 years. Results. The OLED screen had a constant time delay from the onset of the trigger signal to the start of the luminescence change. The delay during the reversal phase from black to white for the pattern was 1.0 msec on the cathode-ray tube (CRT screen and 0.5 msec on the OLED screen. No significant differences in the amplitudes of P100 and the implicit times of N75 and P100 were observed in the p-VEPs elicited by the CRT and the OLED screens. Conclusion. The OLED screen can be used as a visual stimulator to elicit p-VEPs; however the time delay and the specific properties in the luminance change must be taken into account.

  12. Engaging Young Children in Research through Photo Elicitation

    Science.gov (United States)

    Pyle, Angela

    2013-01-01

    Embracing the new sociology of childhood, this paper describes a participatory research method built on a belief in the competency of young children. The paper begins with a critical review of the photo elicitation literature exploring the varied levels of children's participation. Drawing on the strengths of the previous research, a multi-step…

  13. Pattern visual evoked potentials elicited by organic electroluminescence screen.

    Science.gov (United States)

    Matsumoto, Celso Soiti; Shinoda, Kei; Matsumoto, Harue; Funada, Hideaki; Sasaki, Kakeru; Minoda, Haruka; Iwata, Takeshi; Mizota, Atsushi

    2014-01-01

    To determine whether organic electroluminescence (OLED) screens can be used as visual stimulators to elicit pattern-reversal visual evoked potentials (p-VEPs). Checkerboard patterns were generated on a conventional cathode-ray tube (S710, Compaq Computer Co., USA) screen and on an OLED (17 inches, 320 × 230 mm, PVM-1741, Sony, Tokyo, Japan) screen. The time course of the luminance changes of each monitor was measured with a photodiode. The p-VEPs elicited by these two screens were recorded from 15 eyes of 9 healthy volunteers (22.0 ± 0.8 years). The OLED screen had a constant time delay from the onset of the trigger signal to the start of the luminescence change. The delay during the reversal phase from black to white for the pattern was 1.0 msec on the cathode-ray tube (CRT) screen and 0.5 msec on the OLED screen. No significant differences in the amplitudes of P100 and the implicit times of N75 and P100 were observed in the p-VEPs elicited by the CRT and the OLED screens. The OLED screen can be used as a visual stimulator to elicit p-VEPs; however the time delay and the specific properties in the luminance change must be taken into account.

  14. Conditioned craving cues elicit an automatic approach tendency

    NARCIS (Netherlands)

    van Gucht, D.; Vansteenwegen, D.; Van den Bergh, O.; Beckers, T.

    2008-01-01

    In two experiments, we used a Pavlovian differential conditioning procedure to induce craving for chocolate. As a result of repeated pairing with chocolate intake, initially neutral cues came to elicit an automatic approach tendency in a speeded stimulus-response compatibility reaction time task.

  15. Eliciting and Applying Local Research Knowledge for Peacebuilding ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    gs

    Carnegie Corporation of New York (CCNY) and the International Development Research Centre (IDRC) are pleased to announce a jointly-funded research initiative Eliciting and Applying Local Research. Knowledge for Peacebuilding and Statebuilding. The research initiative seeks to increase the level of recognition and ...

  16. Elicitation of Pharmacologically Active Substances in Intact Medical Plant

    Czech Academy of Sciences Publication Activity Database

    Kužel, S.; Vydra, J.; Tříska, Jan; Vrchotová, Naděžda; Hrubý, Martin; Cígler, P.

    2009-01-01

    Roč. 57, č. 17 (2009), s. 7907-7911 ISSN 0021-8561 Institutional research plan: CEZ:AV0Z60870520; CEZ:AV0Z40500505 Keywords : elicitation * medical plant * Echinacea purpurea * secondary metabolite * foliar application * phenolics Subject RIV: CB - Analytical Chemistry, Separation Impact factor: 2.469, year: 2009

  17. Extinction and renewal of cue-elicited reward-seeking.

    Science.gov (United States)

    Bezzina, Louise; Lee, Jessica C; Lovibond, Peter F; Colagiuri, Ben

    2016-12-01

    Reward cues can contribute to overconsumption of food and drugs and can relapse. The failure of exposure therapies to reduce overconsumption and relapse is generally attributed to the context-specificity of extinction. However, no previous study has examined whether cue-elicited reward-seeking (as opposed to cue-reactivity) is sensitive to context renewal. We tested this possibility in 160 healthy volunteers using a Pavlovian-instrumental transfer (PIT) design involving voluntary responding for a high value natural reward (chocolate). One reward cue underwent Pavlovian extinction in the same (Group AAA) or different context (Group ABA) to all other phases. This cue was compared with a second non-extinguished reward cue and an unpaired control cue. There was a significant overall PIT effect with both reward cues eliciting reward-seeking on test relative to the unpaired cue. Pavlovian extinction substantially reduced this effect, with the extinguished reward cue eliciting less reward-seeking than the non-extinguished reward cue. Most interestingly, extinction of cue-elicited reward-seeking was sensitive to renewal, with extinction less effective for reducing PIT when conducted in a different context. These findings have important implications for extinction-based interventions for reducing maladaptive reward-seeking in practice. Copyright © 2016 Elsevier Ltd. All rights reserved.

  18. Glycopeptide Antibiotics Potently Inhibit Cathepsin L in the Late Endosome/Lysosome and Block the Entry of Ebola Virus, Middle East Respiratory Syndrome Coronavirus (MERS-CoV), and Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV)*

    Science.gov (United States)

    Zhou, Nan; Pan, Ting; Zhang, Junsong; Li, Qianwen; Zhang, Xue; Bai, Chuan; Huang, Feng; Peng, Tao; Zhang, Jianhua; Liu, Chao; Tao, Liang; Zhang, Hui

    2016-01-01

    Ebola virus infection can cause severe hemorrhagic fever with a high mortality in humans. The outbreaks of Ebola viruses in 2014 represented the most serious Ebola epidemics in history and greatly threatened public health worldwide. The development of additional effective anti-Ebola therapeutic agents is therefore quite urgent. In this study, via high throughput screening of Food and Drug Administration-approved drugs, we identified that teicoplanin, a glycopeptide antibiotic, potently prevents the entry of Ebola envelope pseudotyped viruses into the cytoplasm. Furthermore, teicoplanin also has an inhibitory effect on transcription- and replication-competent virus-like particles, with an IC50 as low as 330 nm. Comparative analysis further demonstrated that teicoplanin is able to block the entry of Middle East respiratory syndrome (MERS) and severe acute respiratory syndrome (SARS) envelope pseudotyped viruses as well. Teicoplanin derivatives such as dalbavancin, oritavancin, and telavancin can also inhibit the entry of Ebola, MERS, and SARS viruses. Mechanistic studies showed that teicoplanin blocks Ebola virus entry by specifically inhibiting the activity of cathepsin L, opening a novel avenue for the development of additional glycopeptides as potential inhibitors of cathepsin L-dependent viruses. Notably, given that teicoplanin has routinely been used in the clinic with low toxicity, our work provides a promising prospect for the prophylaxis and treatment of Ebola, MERS, and SARS virus infection. PMID:26953343

  19. Glycopeptide Antibiotics Potently Inhibit Cathepsin L in the Late Endosome/Lysosome and Block the Entry of Ebola Virus, Middle East Respiratory Syndrome Coronavirus (MERS-CoV), and Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV).

    Science.gov (United States)

    Zhou, Nan; Pan, Ting; Zhang, Junsong; Li, Qianwen; Zhang, Xue; Bai, Chuan; Huang, Feng; Peng, Tao; Zhang, Jianhua; Liu, Chao; Tao, Liang; Zhang, Hui

    2016-04-22

    Ebola virus infection can cause severe hemorrhagic fever with a high mortality in humans. The outbreaks of Ebola viruses in 2014 represented the most serious Ebola epidemics in history and greatly threatened public health worldwide. The development of additional effective anti-Ebola therapeutic agents is therefore quite urgent. In this study, via high throughput screening of Food and Drug Administration-approved drugs, we identified that teicoplanin, a glycopeptide antibiotic, potently prevents the entry of Ebola envelope pseudotyped viruses into the cytoplasm. Furthermore, teicoplanin also has an inhibitory effect on transcription- and replication-competent virus-like particles, with an IC50 as low as 330 nm Comparative analysis further demonstrated that teicoplanin is able to block the entry of Middle East respiratory syndrome (MERS) and severe acute respiratory syndrome (SARS) envelope pseudotyped viruses as well. Teicoplanin derivatives such as dalbavancin, oritavancin, and telavancin can also inhibit the entry of Ebola, MERS, and SARS viruses. Mechanistic studies showed that teicoplanin blocks Ebola virus entry by specifically inhibiting the activity of cathepsin L, opening a novel avenue for the development of additional glycopeptides as potential inhibitors of cathepsin L-dependent viruses. Notably, given that teicoplanin has routinely been used in the clinic with low toxicity, our work provides a promising prospect for the prophylaxis and treatment of Ebola, MERS, and SARS virus infection. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  20. In vitro activities of the new semisynthetic glycopeptide telavancin (TD-6424), vancomycin, daptomycin, linezolid, and four comparator agents against anaerobic gram-positive species and Corynebacterium spp.

    Science.gov (United States)

    Goldstein, Ellie J C; Citron, Diane M; Merriam, C Vreni; Warren, Yumi A; Tyrrell, Kerin L; Fernandez, Helen T

    2004-06-01

    Telavancin is a new semisynthetic glycopeptide anti-infective with multiple mechanisms of action, including inhibition of bacterial membrane phospholipid synthesis and inhibition of bacterial cell wall synthesis. We determined the in vitro activities of telavancin, vancomycin, daptomycin, linezolid, quinupristin-dalfopristin, imipenem, piperacillin-tazobactam, and ampicillin against 268 clinical isolates of anaerobic gram-positive organisms and 31 Corynebacterium strains using agar dilution methods according to National Committee for Clinical Laboratory Standards procedures. Plates with daptomycin were supplemented with Ca(2+) to 50 mg/liter. The MICs at which 90% of isolates tested were inhibited (MIC(90)s) for telavancin and vancomycin were as follows: Actinomyces spp. (n = 45), 0.25 and 1 microg/ml, respectively; Clostridium difficile (n = 14), 0.25 and 1 microg/ml, respectively; Clostridium ramosum (n = 16), 1 and 4 microg/ml, respectively; Clostridium innocuum (n = 15), 4 and 16 microg/ml, respectively; Clostridium clostridioforme (n = 15), 8 and 1 microg/ml, respectively; Eubacterium group (n = 33), 0.25 and 2 microg/ml, respectively; Lactobacillus spp. (n = 26), 0.5 and 4 microg/ml, respectively; Propionibacterium spp. (n = 34), 0.125 and 0.5 microg/ml, respectively; Peptostreptococcus spp. (n = 52), 0.125 and 0.5 microg/ml, respectively; and Corynebacterium spp. (n = 31), 0.03 and 0.5 microg/ml, respectively. The activity of TD-6424 was similar to that of quinupristin-dalfopristin for most strains except C. clostridioforme and Lactobacillus casei, where quinupristin-dalfopristin was three- to fivefold more active. Daptomycin had decreased activity (MIC > 4 microg/ml) against 14 strains of Actinomyces spp. and all C. ramosum, Eubacterium lentum, and Lactobacillus plantarum strains. Linezolid showed decreased activity (MIC > 4 microg/ml) against C. ramosum, two strains of C. difficile, and 15 strains of Lactobacillus spp. Imipenem and piperacillin

  1. An alternative approach for eliciting willingness-to-pay

    Directory of Open Access Journals (Sweden)

    Laura J. Damschroder

    2007-04-01

    Full Text Available Open-ended methods that elicit willingness-to-pay (WTP in terms of absolute dollars often result in high rates of questionable and highly skewed responses, insensitivity to changes in health state, and raise an ethical issue related to its association with personal income. We conducted a 2x2 randomized trial over the Internet to test 4 WTP formats: 1 WTP in dollars; 2 WTP as a percentage of financial resources; 3 WTP in terms of monthly payments; and 4 WTP as a single lump-sum amount. WTP as a percentage of financial resources generated fewer questionable values, had better distribution properties, greater sensitivity to severity of health states, and was not associated with income. WTP elicited on a monthly basis also showed promise.

  2. Elicitation of preferences for improvements in ostomy pouches

    DEFF Research Database (Denmark)

    Bonnichsen, Ole

    This paper attempts to examine and measure ostomates’ preferences for improvements in ostomy pouches. Described are the study design, elicitation procedure and resulting preference structure of the Swedish ostomate sample. The method used to elicit the preferences is a Discrete Choice Experiment...... (DCE), where respondents are asked to choose between alternatives in choice sets. Each alternative is comprised of a number of attributes relating to the adhesive, filter and flexibility of ostomy pouches. The choice between alternatives made by the respondent implies an implicit trade-off between...... the attributes and allows for the estimation of individuals’ Willingness to Pay (WTP) for the attributes of ostomy pouches when cost is included as an attribute. The data consists of 254 ostomates responding to the survey. The respondents have positive WTP for all improvement attributes presented to them...

  3. Preference Elicitation and Negotiation in a Group Recommender System

    OpenAIRE

    Álvarez Márquez , Jesús ,; Ziegler , Jurgen

    2015-01-01

    International audience; We present a novel approach to group recommender systems that better takes into account the social interaction in a group when formulating, discussing and negotiating the features of the item to be jointly selected. Our approach provides discussion support in a collaborative preference elicitation and negotiation process. Individual preferences are continuously aggregated and immediate feedback of the resulting recommendations is provided. We also support the last stag...

  4. A Step-Wise Approach to Elicit Triangular Distributions

    Science.gov (United States)

    Greenberg, Marc W.

    2013-01-01

    Adapt/combine known methods to demonstrate an expert judgment elicitation process that: 1.Models expert's inputs as a triangular distribution, 2.Incorporates techniques to account for expert bias and 3.Is structured in a way to help justify expert's inputs. This paper will show one way of "extracting" expert opinion for estimating purposes. Nevertheless, as with most subjective methods, there are many ways to do this.

  5. Graph and Network for Model Elicitation (GNOME Phase 2)

    Science.gov (United States)

    2013-02-01

    GRAPH AND NETWORK FOR MODEL ELICITATION (GNOME PHASE II) CUBRC FEBRUARY 2013 FINAL TECHNICAL REPORT APPROVED FOR...NUMBER 00 5f. WORK UNIT NUMBER 01 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) CUBRC 4455 Genesee St. Buffalo, NY 14225 8. PERFORMING...Explorer Since the previous version of GNOME was developed as an Eclipse RCP plug-in, it allowed CUBRC to develop the Model Explorer separately without

  6. Anticipating requirements changes-using futurology in requirements elicitation

    OpenAIRE

    Pimentel, João Henrique; Santos, Emanuel; Castro, Jaelson; Franch Gutiérrez, Javier

    2012-01-01

    It is well known that requirements changes in a later phase of software developments is a major source of software defects and costs. Thus, the need of techniques to control or reduce the amount of changes during software development projects. The authors advocate the use of foresight methods as a valuable input to requirements elicitation, with the potential to decrease the number of changes that would be required after deployment, by anticipating them. In this paper, the authors define a pr...

  7. Neutrosophic Logic for Mental Model Elicitation and Analysis

    Directory of Open Access Journals (Sweden)

    Karina Pérez-Teruel

    2014-03-01

    Full Text Available Mental models are personal, internal representations of external reality that people use to interact with the world around them. They are useful in multiple situations such as muticriteria decision making, knowledge management, complex system learning and analysis. In this paper a framework for mental models elicitation and analysis based on neutrosophic Logic is presented. An illustrative example is provided to show the applicability of the proposal. The paper ends with conclusion future research directions.

  8. Autobiographical memories of young adults elicited by positive musical stimuli

    OpenAIRE

    Gonçalves, Ana Margarida Silva

    2015-01-01

    Dissertação de mestrado integrado em Psicologia Studies on autobiographical memories have shown the presence of three main components: childhood amnesia, recency effect and reminiscence bump (Rubin, 1986). Previous research suggests that autobiographical memories elicited by positive stimuli are associated with highly, specific and generally pleasant episodes (Krumhansl & Zupnick, 2013). Music has an important and highly emotional and social role in individual’s lives. The p...

  9. Incentives for Truthful Information Elicitation of Continuous Signals

    OpenAIRE

    Radanovic, Goran; Faltings, Boi

    2014-01-01

    We consider settings where a collective intelligence is formed by aggregating information contributed from many independent agents, such as product reviews, community sensing, or opinion polls. We propose a novel mechanism that elicits both private signals and beliefs. The mechanism extends the previous versions of the Bayesian Truth Serum (the original BTS, the RBTS, and the multi-valued BTS), by allowing small populations and non-binary private signals, while not requiring additional assump...

  10. Interviewing strategically to elicit admissions from guilty suspects

    OpenAIRE

    Tekin, Serra; Granhag, Pär Anders; Strömwall, Leif; Giolla, Erik Mac; Vrij, Aldert; Hartwig, Maria

    2015-01-01

    In this article we introduce a novel interviewing tactic to elicit admissions from guilty suspects. By influencing the suspects’ perception of the amount of evidence the interviewer holds against them, we aimed to shift the suspects’ counterinterrogation strategies from less to more forthcoming. The proposed tactic (SUE-Confrontation) is a development of the Strategic Use of Evidence (SUE) framework and aims to affect the suspects’ perception by confronting them with statement-evidence incons...

  11. The Lookahead Principle for Preference Elicitation: Experimental Results

    OpenAIRE

    Viappiani, Paolo; Faltings, Boi; Pu, Pearl

    2006-01-01

    Preference-based search is the problem of finding an item that matches best with a user's preferences. User studies show that example-based tools for preference-based search can achieve significantly higher accuracy when they are complemented with suggestions chosen to inform users about the available choices. We discuss the problem of eliciting preferences in example-based tools and present the lookahead principle for generating suggestions. We compare two different implementations of this p...

  12. Non-Functional Requirements Elicitation and Incorporation into Class Diagrams

    OpenAIRE

    Song , Xiaoyu; Duan , Zhenhua; Tian , Cong

    2010-01-01

    International audience; Top-quality software architecture should consider both functional and non-functional aspects of systems and their association. In the the existing literature, considerable efforts have been directed at functional requirement analysis and design, regardless of the non-functional aspects. This disassociation makes architecture comprehension and evolution hard. This paper proposes a strategy on how to elicit non-functional requirements and incorporate them into the design...

  13. Saturated Zone Flow and Transport Expert Elicitation Project

    Energy Technology Data Exchange (ETDEWEB)

    Coppersmith, Kevin J.; Perman, Roseanne C.

    1998-01-01

    This report presents results of the Saturated Zone Flow and Transport Expert Elicitation (SZEE) project for Yucca Mountain, Nevada. This project was sponsored by the US Department of Energy (DOE) and managed by Geomatrix Consultants, Inc. (Geomatrix), for TRW Environmental Safety Systems, Inc. The DOE's Yucca Mountain Site Characterization Project (referred to as the YMP) is intended to evaluate the suitability of the site for construction of a mined geologic repository for the permanent disposal of spent nuclear fuel and high-level radioactive waste. The SZEE project is one of several that involve the elicitation of experts to characterize the knowledge and uncertainties regarding key inputs to the Yucca Mountain Total System Performance Assessment (TSPA). The objective of the current project was to characterize the uncertainties associated with certain key issues related to the saturated zone system in the Yucca Mountain area and downgradient region. An understanding of saturated zone processes is critical to evaluating the performance of the potential high-level nuclear waste repository at Yucca Mountain. A major goal of the project was to capture the uncertainties involved in assessing the saturated flow processes, including uncertainty in both the models used to represent the physical processes controlling saturated zone flow and transport, and the parameter values used in the models. So that the analysis included a wide range of perspectives, multiple individual judgments were elicited from members of an expert panel. The panel members, who were experts from within and outside the Yucca Mountain project, represented a range of experience and expertise. A deliberate process was followed in facilitating interactions among the experts, in training them to express their uncertainties, and in eliciting their interpretations. The resulting assessments and probability distributions, therefore, provide a reasonable aggregate representation of the knowledge and

  14. Elicitation of andrographolide in the suspension cultures of Andrographis paniculata.

    Science.gov (United States)

    Gandi, Suryakala; Rao, Kiranmayee; Chodisetti, Bhuvaneswari; Giri, Archana

    2012-12-01

    Andrographis paniculata belonging to the family Acanthaceae produces a group of diterpene lactones, one of which is the pharmaceutically important-andrographolide. It is known to possess various important biological properties like anticancer, anti-HIV, anti-inflammatory, etc. This is the first report on the production of andrographolide in the cell suspension cultures of Andrographis paniculata by 'elicitation'. Elicitation was attempted to enhance the andrographolide content in the suspension cultures of Andrographis paniculata and also to ascertain its stimulation under stress conditions or in response to pathogen attack. The maximum andrographolide production was found to be 1.53 mg/g dry cell weight (DCW) at the end of stationary phase during the growth curve. The biotic elicitors (yeast, Escherichia coli, Bacillus subtilis, Agrobacterium rhizogenes 532 and Agrobacterium tumefaciens C 58) were more effective in eliciting the response when compared to the abiotic elicitors (CdCl(2), AgNO(3), CuCl(2) and HgCl(2)). Yeast has shown to stimulate maximum accumulation of 13.5 mg/g DCW andrographolide, which was found to be 8.82-fold higher than the untreated cultures.

  15. Role of local neurons in cerebrocortical vasodilation elicited from cerebellum

    International Nuclear Information System (INIS)

    Iadecola, C.; Arneric, S.P.; Baker, H.D.; Tucker, L.W.; Reis, D.J.

    1987-01-01

    The vasodilation elicited in cerebral cortex by stimulation of the cerebellar fastigial nucleus (FN) is mediated by input pathways coming from the basal forebrain. The authors studied whether these pathways mediate the cortical vasodilation via a direct action on local blood vessels or via interposed local neurons. Neurons were destroyed in the primary sensory cortex by local microinjection of the excitotoxin ibotenic acid (IBO). Five days later rats were anesthetized, paralyzed, and ventilated. Arterial pressure and blood gases were controlled, and FN was stimulated electrically. Local cerebral blood flow (LCBF) was measured using the [ 14 C]iodoantipyrine technique with autoradiography. Five days after IBO, neurons were destroyed in a restricted cortical area, and afferent fibers and terminals were preserved. The selectivity of the neuronal loss was established by histological and biochemical criteria and by transport of horseradish, peroxidase from or into the lesion. Within the lesion, resting LCBF was unaffected, but the increase in LCBF evoked from the FN was abolished. In contrast the vasodilation elicited by hypercapnia was preserved. In the rest of the brain the vasodilation elicited from FN was largely unaffected. The authors conclude that the vasodilation evoked from FN in cerebral cortex depends on the integrity of a restricted population of local neurons that interact with the local microvasculature

  16. State-of-the-Art Prescriptive Criteria Weight Elicitation

    Directory of Open Access Journals (Sweden)

    Mona Riabacke

    2012-01-01

    Full Text Available Comparatively few of the vast amounts of decision analytical methods suggested have been widely spread in actual practice. Some approaches have nevertheless been more successful in this respect than others. Quantitative decision making has moved from the study of decision theory founded on a single criterion towards decision support for more realistic decision-making situations with multiple, often conflicting, criteria. Furthermore, the identified gap between normative and descriptive theories seems to suggest a shift to more prescriptive approaches. However, when decision analysis applications are used to aid prescriptive decision-making processes, additional demands are put on these applications to adapt to the users and the context. In particular, the issue of weight elicitation is crucial. There are several techniques for deriving criteria weights from preference statements. This is a cognitively demanding task, subject to different biases, and the elicited values can be heavily dependent on the method of assessment. There have been a number of methods suggested for assessing criteria weights, but these methods have properties which impact their applicability in practice. This paper provides a survey of state-of-the-art weight elicitation methods in a prescriptive setting.

  17. Conditioned responses elicited by experimentally produced cues for smoking.

    Science.gov (United States)

    Mucha, R F; Pauli, P; Angrilli, A

    1998-03-01

    Several theories of drug-craving postulate that a signal for drug elicits conditioned responses. However, depending on the theory, a drug cue is said to elicit drug similar, drug compensatory, positive motivational, and negative motivational effects. Since animal data alone cannot tease apart the relative importance of different cue-related processes in the addict, we developed and examined a model of drug cues in the human based on a two-sound, differential conditioning procedure using smoking as the reinforcer. After multiple pairings of a sound with smoking, there was a preference for the smoking cue on a conditioned preference test. The acute effects of smoking (increased heart rate, respiration rate, skin conductance level, skin conductance fluctuations, EEG beta power and trapezius EMG, decreased alpha power) were not affected by the smoking cue, although subjects drew more on their cigarette in the presence of the smoking cue than in the presence of a control cue. Moreover, the cue did not change baseline behaviour except for a possible increase in EEG beta power and an increase in trapezius EMG at about the time when smoking should have occurred. The findings confirm the value of experimental models of drug cues in the human for comparing different cue phenomena in the dependent individual. They indicate that an acquired signal for drug in the human may elicit incentive motivational effects and associated preparatory motor responses in addition to possible conditioned tolerance.

  18. Risk-Informed SSCs Categorization: Elicitation Method of Expert's Opinion

    International Nuclear Information System (INIS)

    Hwang, Mee Jeong; Yang, Joon Eon; Kim, Kil Yoo

    2005-01-01

    The regulations have been performing by deterministic way since nuclear power plants have been operating. However, some SSCs identified as safety-significance by deterministic way, were turned out to be low or non safety-significant and some SSCs identified as non-safety significance were turned out to be high safety-significant according to the results of PSA. Considering these risk insights, Regulatory Guide 1.174 and 10CFR50.69 were drawn up, and we can re-categorize the SSCs according to their safety significance. Therefore, a study and an interest about the risk-informed SSCs re-categorization and treatment has been continued. The objective of this regulatory initiative is to adjust the scope of equipment subject to special regulatory treatment to better focus licensee and regulatory attention and resources on equipment that has safety significance. Current most regulations define the plant equipment necessary to meet deterministic regulatory basis as 'safety-related.' This equipment is subject to special treatment regulations. Other plant equipment is categorized as 'non-safety related,' and is not subject to a select number of special treatment requirement or a subset of those requirement. However, risk information is not a magic tool making a decision but a supporting tool to categorize SSCs. This is because only small parts of a plant are modeled in PSA model. Thus, engineering and deterministic judgments are also used for risk-informed SSCs categorization, and expert opinion elicitation is very important for risk-informed SSCs categorization. Therefore, we need a rational method to elicit the expert's opinions, and in this study, we developed a systematic method for expert elicitation to categorize the nuclear power plants' SSCs. Current states for SSCs categorization of the USA and the existing methods for expert elicitation were surveyed and more systematic way eliciting the expert opinions and combining was developed. To validate the developed method

  19. Targeting MUC1 mediated tumor stromal metabolic interaction in Triple negative Breast Cancer

    Science.gov (United States)

    2016-11-01

    were suspended in 200 µl of LC-MS grade water and centrifuged to collect the water - soluble supernatants. The combined supernatants were concentrated...suspended in equal volumes of LC-MS grade water and 10 µl were utilized for LC-MS/MS using multiple reaction monitoring (MRM) method described...AcCoA), α-ketoglutarate (α-KG), solute carrier family 1 member 5 (SLC1A5), tricarboxyic acid cycle (TCA cycle), transcription factor (TF) and

  20. Targeting MUC1-Mediated Tumor-Stromal Metabolic Interaction in Triple-Negative Breast Cancer

    Science.gov (United States)

    2016-11-01

    were suspended in 200 µl of LC-MS grade water and centrifuged to collect the water - soluble supernatants. The combined supernatants were concentrated...suspended in equal volumes of LC-MS grade water and 10 µl were utilized for LC-MS/MS using multiple reaction monitoring (MRM) method described...AcCoA), α-ketoglutarate (α-KG), solute carrier family 1 member 5 (SLC1A5), tricarboxyic acid cycle (TCA cycle), transcription factor (TF) and

  1. Effect of MUC1 Expression on EGFR Endocytosis and Degradation in Human Breast Cancer Cell Lines

    Science.gov (United States)

    2007-04-01

    AR), heparin-binding EGF (HB-EGF), betacellulin (BTC), epiregulin ( EPR ), and epigen [reviewed in (Schroeder & Lee, 1997) and (Strachan et al., 2001...of erbB1, it also promotes its internalization. This apparent paradox may be explained by one of two non-exclusive hypotheses. The first is that

  2. Human Milk Blocks DC-SIGN-Pathogen Interaction via MUC1

    NARCIS (Netherlands)

    Koning, Nathalie; Kessen, Sabine F M; Van Der Voorn, J Patrick; Appelmelk, Ben J; Jeurink, Prescilla V; Knippels, Leon M J; Garssen, Johan; Van Kooyk, Yvette

    2015-01-01

    Beneficial effects of breastfeeding are well-recognized and include both immediate neonatal protection against pathogens and long-term protection against allergies and autoimmune diseases. Although several proteins have been identified to have anti-viral or anti-bacterial effects like secretory IgA

  3. A Novel Association and Therapeutic Targeting of Neuropilin-1 and MUC1 in Pancreatic Cancer

    Science.gov (United States)

    2015-12-01

    be potentially translated to human clinical trials. Other Achievements References 1. Besmer DM, Curry JM, Roy LD, Tinder TL, Sahraei M, Schettini J...containing protein tyrosine phosphatase 2. J Cell Sci 2009, 122(Pt 18):3385-3392. 4. Roy LD, Sahraei M, Subramani DB, Besmer D, Nath S, Tinder TL, Bajaj E

  4. Estimating unknown parameters in haemophilia using expert judgement elicitation.

    Science.gov (United States)

    Fischer, K; Lewandowski, D; Janssen, M P

    2013-09-01

    The increasing attention to healthcare costs and treatment efficiency has led to an increasing demand for quantitative data concerning patient and treatment characteristics in haemophilia. However, most of these data are difficult to obtain. The aim of this study was to use expert judgement elicitation (EJE) to estimate currently unavailable key parameters for treatment models in severe haemophilia A. Using a formal expert elicitation procedure, 19 international experts provided information on (i) natural bleeding frequency according to age and onset of bleeding, (ii) treatment of bleeds, (iii) time needed to control bleeding after starting secondary prophylaxis, (iv) dose requirements for secondary prophylaxis according to onset of bleeding, and (v) life-expectancy. For each parameter experts provided their quantitative estimates (median, P10, P90), which were combined using a graphical method. In addition, information was obtained concerning key decision parameters of haemophilia treatment. There was most agreement between experts regarding bleeding frequencies for patients treated on demand with an average onset of joint bleeding (1.7 years): median 12 joint bleeds per year (95% confidence interval 0.9-36) for patients ≤ 18, and 11 (0.8-61) for adult patients. Less agreement was observed concerning estimated effective dose for secondary prophylaxis in adults: median 2000 IU every other day The majority (63%) of experts expected that a single minor joint bleed could cause irreversible damage, and would accept up to three minor joint bleeds or one trauma related joint bleed annually on prophylaxis. Expert judgement elicitation allowed structured capturing of quantitative expert estimates. It generated novel data to be used in computer modelling, clinical care, and trial design. © 2013 John Wiley & Sons Ltd.

  5. Structured tradeoffs preference elicitation: Evaluating CRWMS design and operations

    International Nuclear Information System (INIS)

    Hartman, H.

    1994-01-01

    Preliminary studies over the past few years have yielded multiple design and operations alternatives for the planned Civilian Radioactive Waste Management System (CRWMS). Waste isolation, pre-closure health and safety, and life cycle cost are among the many factors considered in developing these alternatives. The task of CRWMS designers is complicated by substantial heat and nuclear radiation energy output of the spent nuclear fuel and high level waste intended for disposal in an underground repository. Not only must the usual effectiveness, operability and cost objectives be balanced, but done so in the context of a constantly changing environment. Particular alternatives sometimes are favored by virtue of their outstanding performance relative to one of these factors. The Ultimate success of the potential repository, however, depends on reaching a defensible and traceable final decision through simultaneous and systematic weighing of all relevant factors. This paper documents the outcome of Structured Tradeoffs Preference (STP) elicitation as a method for the simultaneous and systematic weighing of factors relevant to repository thermal loading, waste package (WP) design, and emplacement mode decisions. The study provided a low-cost early indication of directions of further research on CRWMS design and operations likely to be most fruitful. The method of STP elicitation was utilized to avoid potential biases documented in other efforts which use only unstructured decision making, or open-quotes well-considered judgmentclose quotes. The STP elicitation procedure presented here complements the use of a parameter network-model pyramid suggested elsewhere in this proceedings to provide a framework for precisely articulating technical questions needing answers. It also forms an independent crosscheck of systems engineering study results and performance assessment modeling

  6. Sample Size for Measuring Grammaticality in Preschool Children from Picture-Elicited Language Samples

    Science.gov (United States)

    Eisenberg, Sarita L.; Guo, Ling-Yu

    2015-01-01

    Purpose: The purpose of this study was to investigate whether a shorter language sample elicited with fewer pictures (i.e., 7) would yield a percent grammatical utterances (PGU) score similar to that computed from a longer language sample elicited with 15 pictures for 3-year-old children. Method: Language samples were elicited by asking forty…

  7. Graphical User Interfaces Reverse Engineering for Requirements Elicitation - Literature Review

    Directory of Open Access Journals (Sweden)

    Carol Jaimes

    2016-06-01

    Full Text Available This paper exhibits a synthesis of the use of legacy systems GUI reverse engineering as a tool to software requirements elicitation. It presents a literature review describing the approaches related to the topic. This work primary goal is to determine the major investigations in this area, and if there are techniques focused exclusively on the observation of the legacy applications GUI to obtain software requirements in a standard format, without the use of source code, data structures, documentation or sophisticated algorithms for the application analysis.

  8. Electronic health records: eliciting behavioral health providers' beliefs.

    Science.gov (United States)

    Shank, Nancy; Willborn, Elizabeth; Pytlikzillig, Lisa; Noel, Harmonijoie

    2012-04-01

    Interviews with 32 community behavioral health providers elicited perceived benefits and barriers of using electronic health records. Themes identified were (a) quality of care, (b) privacy and security, and (c) delivery of services. Benefits to quality of care were mentioned by 100% of the providers, and barriers by 59% of providers. Barriers involving privacy and security concerns were mentioned by 100% of providers, and benefits by 22%. Barriers to delivery of services were mentioned by 97% of providers, and benefits by 66%. Most providers (81%) expressed overall positive support for electronic behavioral health records.

  9. Prior Elicitation, Assessment and Inference with a Dirichlet Prior

    Directory of Open Access Journals (Sweden)

    Michael Evans

    2017-10-01

    Full Text Available Methods are developed for eliciting a Dirichlet prior based upon stating bounds on the individual probabilities that hold with high prior probability. This approach to selecting a prior is applied to a contingency table problem where it is demonstrated how to assess the prior with respect to the bias it induces as well as how to check for prior-data conflict. It is shown that the assessment of a hypothesis via relative belief can easily take into account what it means for the falsity of the hypothesis to correspond to a difference of practical importance and provide evidence in favor of a hypothesis.

  10. Eliciting Audience's Experience to Improve Interactive Art Installation

    DEFF Research Database (Denmark)

    Baharin, Hanif; Morrison, Ann

    2006-01-01

    Designing with the users in mind is one of the widely accepted design practices in the Interaction Design field. On the other hand, it can be said that audience's experience is the heart of an interactive art. Since Interaction Design has shown that user's involvement in the design process can...... be beneficial, it is speculated that involving the audiences in the creative process of developing an interactive art piece can make the artist improve the art in general and the audience's experience in particular. In this paper, the experience of eliciting the experience of the audiences of an interactive art...

  11. Defining DSL design principles for enhancing the requirements elicitation process

    Directory of Open Access Journals (Sweden)

    Gustavo Arroyo

    2012-03-01

    Full Text Available La Elicitación de Requisitos propicia el entendimiento de las necesidades de los usuarios con respecto a un desarrollo de software. Los métodos que se emplean provienen de las ciencias sociales por lo que se carece de una retroalimentación ejecutable. Consecuentemente, la primera versión del software podría no cumplir con las expectativas. El uso de DSLs como herramientas para el descubrimiento de requisitos es una idea aceptada, desafortunadamente, muy pocos trabajos en la literatura se enfocan en la definición de principios de diseño de DSLs. En este trabajo planteamos principios de diseño de DSLs orientados a la elicitación de requisitos, enseguida, generamos casos de prueba en ANTLR, Ruby y Curry. También, enunciamos el perfil que debe tener el nuevo analista de software. Con ello, se incrementa la retroalimentación entre los involucrados en el desarrollo de software y se mejora el producto.Requirements elicitation is concerned with learning and understanding the needs of users w.r.t. a new software development. Frequently the methods employed for requirements elicitation are adapted from areas like social sciences that do not include executable (prototype based on feedback. As a consequence, it is relatively common to discover that the first release does not fit the requirements defined at the beginning of the project. Using domain-specific languages (DSLs as an auxiliary tool for requirements elicitation is a commonly well accepted idea. Unfortunately, there are few works in the literature devoted to the definition of design principles for DSLs to be experienced in the frameworks for DSL developing such as ANTLR, Ruby, and Curry. We propose design principles for the DSL development (regardless of paradigm which are sufficient to model the domain in a requirements phase. Further more we enunciate a new profile for the requirements analyst and a set of elicitation steps. The use of DSLs not only giveus an immediate feedback with

  12. Expert Panel Elicitation of Seismicity Following Glaciation in Sweden

    International Nuclear Information System (INIS)

    Hora, Stephen; Jensen, Mikael

    2005-12-01

    The Swedish Radiation Protection Authority, the Swedish Nuclear Power Inspectorate and the Swedish Nuclear Fuel and Waste Management Company have jointly carried out a project on expert panel elicitation on the issue of glacial induced Swedish earthquakes. Following a broad nomination procedure, 5 experts were chosen by a selection committee of 4 professors within Earth sciences disciplines. The 5 experts presented judgments about the frequency of earthquakes greater the magnitude 6 within 10 km for two Swedish sites, Oskarshamn and Forsmark, in connection with a glaciation cycle. The experts' median value vas 0,1 earthquakes for one glaciation cycle

  13. Integrating Effectiveness, Transparency and Fairness into a Value Elicitation Process

    International Nuclear Information System (INIS)

    Fortier, Michael; Sheng, Grant

    2001-01-01

    As part of the evaluation of Canada's proposed nuclear fuel waste disposal concept, the Federal Environmental Assessment and Review Panel (FEARP) undertook an extensive, nation-wide public hearing process. The hearing process itself was contentious and has been criticized on numerous grounds. It is our contention that the fundamental weakness of the FEARP process was that it was designed as an information-based forum, as opposed to a value-based forum.' Our observations and analyses of these hearings indicate that the FEARP envisioned a different purpose and a different outcome of this process than the public in general. As a result, public acceptability for the Concept or even the assessment process itself was not garnered due to a failure in the process to identify, address and incorporate values. To address this, we proposed a seven-step value elicitation process specifically designed to assess public acceptability of the disposal concept. An unfortunate consequence of the flawed public consultation process employed by the FEARP is that it is unclear exactly what it is the public finds unacceptable. Both from discussions and observations, it is difficult to ascertain whether the unacceptability lies with the Concept itself and/or the process by which the Concept was to be assessed. As a result, there is uncertainty as to what questions should be asked and how should the 'unacceptability' be addressed. In other words, does Canada need a new concept? Does Canada need to develop a mechanism for assessing the public acceptability of the Concept? Or both? The inability of the current process to answer such fundamental questions demonstrates the importance of developing an effective public acceptability and consultation process. We submit that, to create an acceptable Public Participation mechanism, it is necessary to found the construction of such a mechanism on the principles of effectiveness, transparency and fairness. Moreover, we believe that the larger decision

  14. Expert Panel Elicitation of Seismicity Following Glaciation in Sweden

    Energy Technology Data Exchange (ETDEWEB)

    Hora, Stephen; Jensen, Mikael (eds.)

    2005-12-15

    The Swedish Radiation Protection Authority, the Swedish Nuclear Power Inspectorate and the Swedish Nuclear Fuel and Waste Management Company have jointly carried out a project on expert panel elicitation on the issue of glacial induced Swedish earthquakes. Following a broad nomination procedure, 5 experts were chosen by a selection committee of 4 professors within Earth sciences disciplines. The 5 experts presented judgments about the frequency of earthquakes greater the magnitude 6 within 10 km for two Swedish sites, Oskarshamn and Forsmark, in connection with a glaciation cycle. The experts' median value vas 0,1 earthquakes for one glaciation cycle.

  15. Unattractive infant faces elicit negative affect from adults.

    Science.gov (United States)

    Schein, Stevie S; Langlois, Judith H

    2015-02-01

    We examined the relationship between infant attractiveness and adult affect by investigating whether differing levels of infant facial attractiveness elicit facial muscle movement correlated with positive and negative affect from adults (N=87) using electromyography. Unattractive infant faces evoked significantly more corrugator supercilii and levator labii superioris movement (physiological correlates of negative affect) than attractive infant faces. These results suggest that unattractive infants may be at risk for negative affective responses from adults, though the relationship between those responses and caregiving behavior remains elusive. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. Integrating Effectiveness, Transparency and Fairness into a Value Elicitation Process

    Energy Technology Data Exchange (ETDEWEB)

    Fortier, Michael; Sheng, Grant [York Univ., Toronto, ON (Canada). Faculty of Environmental Studies; Collins, Alison [York Centre for Applied Sustainability, Toronto, ON (Canada)

    2001-07-01

    As part of the evaluation of Canada's proposed nuclear fuel waste disposal concept, the Federal Environmental Assessment and Review Panel (FEARP) undertook an extensive, nation-wide public hearing process. The hearing process itself was contentious and has been criticized on numerous grounds. It is our contention that the fundamental weakness of the FEARP process was that it was designed as an information-based forum, as opposed to a value-based forum.' Our observations and analyses of these hearings indicate that the FEARP envisioned a different purpose and a different outcome of this process than the public in general. As a result, public acceptability for the Concept or even the assessment process itself was not garnered due to a failure in the process to identify, address and incorporate values. To address this, we proposed a seven-step value elicitation process specifically designed to assess public acceptability of the disposal concept. An unfortunate consequence of the flawed public consultation process employed by the FEARP is that it is unclear exactly what it is the public finds unacceptable. Both from discussions and observations, it is difficult to ascertain whether the unacceptability lies with the Concept itself and/or the process by which the Concept was to be assessed. As a result, there is uncertainty as to what questions should be asked and how should the 'unacceptability' be addressed. In other words, does Canada need a new concept? Does Canada need to develop a mechanism for assessing the public acceptability of the Concept? Or both? The inability of the current process to answer such fundamental questions demonstrates the importance of developing an effective public acceptability and consultation process. We submit that, to create an acceptable Public Participation mechanism, it is necessary to found the construction of such a mechanism on the principles of effectiveness, transparency and fairness. Moreover, we believe that

  17. Emotion elicitation: A comparison of pictures and films

    Directory of Open Access Journals (Sweden)

    Meike Katrin Uhrig

    2016-02-01

    Full Text Available AbstractPictures and film clips are widely used and accepted stimuli to elicit emotions. Based on theoretical arguments it is often assumed that the emotional effects of films exceed those of pictures, but to date this assumption has not been investigated directly. The aim of the present study was to compare pictures and films in terms of their capacity to induce emotions verified by means of explicit measures. Stimuli were (a single pictures presented for 6 s, (b a set of three consecutive pictures with emotionally congruent contents presented for 2 s each, (c short film clips with a duration of 6 s. A total of 144 participants rated their emotion and arousal states following stimulus presentation. Repeated-measures ANOVAs revealed that the film clips and 3-picture version were as effective as the classical 1-picture method to elicit positive emotions, however, modulation towards positive valence was little. Modulation toward negative valence was more effective in general. Film clips were less effective than pictorial stimuli in producing the corresponding emotion states (all p < .001 and were less arousing (all p ≤ .02. Possible reasons for these unexpected results are discussed.

  18. Emotion Elicitation: A Comparison of Pictures and Films.

    Science.gov (United States)

    Uhrig, Meike K; Trautmann, Nadine; Baumgärtner, Ulf; Treede, Rolf-Detlef; Henrich, Florian; Hiller, Wolfgang; Marschall, Susanne

    2016-01-01

    Pictures and film clips are widely used and accepted stimuli to elicit emotions. Based on theoretical arguments it is often assumed that the emotional effects of films exceed those of pictures, but to date this assumption has not been investigated directly. The aim of the present study was to compare pictures and films in terms of their capacity to induce emotions verified by means of explicit measures. Stimuli were (a) single pictures presented for 6 s, (b) a set of three consecutive pictures with emotionally congruent contents presented for 2 s each, (c) short film clips with a duration of 6 s. A total of 144 participants rated their emotion and arousal states following stimulus presentation. Repeated-measures ANOVAs revealed that the film clips and 3-picture version were as effective as the classical 1-picture method to elicit positive emotions, however, modulation toward positive valence was little. Modulation toward negative valence was more effective in general. Film clips were less effective than pictorial stimuli in producing the corresponding emotion states (all p < 0.001) and were less arousing (all p ≤ 0.02). Possible reasons for these unexpected results are discussed.

  19. Experimental elicitation with hydroxyisohexyl-3-cyclohexene carboxaldehyde-containing deodorants.

    Science.gov (United States)

    Jørgensen, Pia Haslund; Jensen, Charlotte Devantier; Rastogi, Suresh; Andersen, Klaus Ejner; Johansen, Jeanne Duus

    2007-03-01

    Hydroxyisohexyl-3-cyclohexene carboxaldehyde (HICC) known as Lyral is a frequent allergen. It is used in more than 50% of marketed deodorants. The aim of the present study was to determine elicitation thresholds for HICC under simulated conditions of deodorant use. 15 patients with previously diagnosed contact allergy to HICC were patch tested with 5 solutions of HICC-scented and HICC-unscented deodorants. Patients and 10 healthy controls performed a use test in the axillae using deodorants scented with HICC in increasing concentrations and unscented deodorants as control. The concentration of HICC was increased every second week (200, 600, and 1800 p.p.m.) until either a reaction developed or for 6 weeks. 14 patients completed the study, and all developed unilateral eczema from the HICC-containing deodorant, while controls were all negative (P= 0.004). In 9/14 patients, a positive use test developed during the first 2 weeks to the deodorant containing 200 p.p.m. HICC. Positive correlations were found between the day of positive use and patch test threshold concentration of the HICC solutions (r= 0.71, P= 0.01) as well as the patch test thresholds of the HICC-scented deodorants (r= 0.74, P= 0.007). In conclusion, HICC elicits allergic contact dermatitis in a high proportion of sensitized individuals at common usage concentrations in deodorants.

  20. Eliciting conditional and unconditional rank correlations from conditional probabilities

    International Nuclear Information System (INIS)

    Morales, O.; Kurowicka, D.; Roelen, A.

    2008-01-01

    Causes of uncertainties may be interrelated and may introduce dependencies. Ignoring these dependencies may lead to large errors. A number of graphical models in probability theory such as dependence trees, vines and (continuous) Bayesian belief nets [Cooke RM. Markov and entropy properties of tree and vine-dependent variables. In: Proceedings of the ASA section on Bayesian statistical science, 1997; Kurowicka D, Cooke RM. Distribution-free continuous Bayesian belief nets. In: Proceedings of mathematical methods in reliability conference, 2004; Bedford TJ, Cooke RM. Vines-a new graphical model for dependent random variables. Ann Stat 2002; 30(4):1031-68; Kurowicka D, Cooke RM. Uncertainty analysis with high dimensional dependence modelling. New York: Wiley; 2006; Hanea AM, et al. Hybrid methods for quantifying and analyzing Bayesian belief nets. In: Proceedings of the 2005 ENBIS5 conference, 2005; Shachter RD, Kenley CR. Gaussian influence diagrams. Manage Sci 1998; 35(5) .] have been developed to capture dependencies between random variables. The input for these models are various marginal distributions and dependence information, usually in the form of conditional rank correlations. Often expert elicitation is required. This paper focuses on dependence representation, and dependence elicitation. The techniques presented are illustrated with an application from aviation safety

  1. Vibrio elicits targeted transcriptional responses from copepod hosts.

    Science.gov (United States)

    Almada, Amalia A; Tarrant, Ann M

    2016-06-01

    Copepods are abundant crustaceans that harbor diverse bacterial communities, yet the nature of their interactions with microbiota are poorly understood. Here, we report that Vibrio elicits targeted transcriptional responses in the estuarine copepod Eurytemora affinis We pre-treated E. affinis with an antibiotic cocktail and exposed them to either a zooplankton specialist (Vibrio sp. F10 9ZB36) or a free-living species (Vibrio ordalii 12B09) for 24 h. We then identified via RNA-Seq a total of 78 genes that were differentially expressed following Vibrio exposure, including homologs of C-type lectins, chitin-binding proteins and saposins. The response differed between the two Vibrio treatments, with the greatest changes elicited upon inoculation with V. sp. F10 We suggest that these differentially regulated genes play important roles in cuticle integrity, the innate immune response, and general stress response, and that their expression may enable E. affinis to recognize and regulate symbiotic vibrios. We further report that V. sp. F10 culturability is specifically altered upon colonization of E. affinis These findings suggest that rather than acting as passive environmental vectors, copepods discriminately interact with vibrios, which may ultimately impact the abundance and activity of copepod-associated bacteria. © FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  2. Interviewing strategically to elicit admissions from guilty suspects.

    Science.gov (United States)

    Tekin, Serra; Granhag, Pär Anders; Strömwall, Leif; Giolla, Erik Mac; Vrij, Aldert; Hartwig, Maria

    2015-06-01

    In this article we introduce a novel interviewing tactic to elicit admissions from guilty suspects. By influencing the suspects' perception of the amount of evidence the interviewer holds against them, we aimed to shift the suspects' counterinterrogation strategies from less to more forthcoming. The proposed tactic (SUE-Confrontation) is a development of the Strategic Use of Evidence (SUE) framework and aims to affect the suspects' perception by confronting them with statement-evidence inconsistencies. Participants (N = 90) were asked to perform several mock criminal tasks before being interviewed using 1 of 3 interview techniques: (a) SUE-Confrontation, (b) Early Disclosure of Evidence, or (c) No Disclosure of Evidence. As predicted, the SUE-Confrontation interview generated more statement-evidence inconsistencies from suspects than the Early Disclosure interview. Importantly, suspects in the SUE-Confrontation condition (vs. Early and No disclosure conditions) admitted more self-incriminating information and also perceived the interviewer to have had more information about the critical phase of the crime (the phase where the interviewer lacked evidence). The findings show the adaptability of the SUE-technique and how it may be used as a tool for eliciting admissions. (c) 2015 APA, all rights reserved).

  3. Eliciting and communicating expert judgments: Methodology and application to nuclear safety

    International Nuclear Information System (INIS)

    Winterfeldt, D. von

    1989-01-01

    The most ambitious and certainly the most extensive formal expert judgment process was the elicitation of numerous events and uncertain quantities for safety issues in five nuclear power plants in the U.S. The general methodology for formal expert elicitations are described. An overview of the expert elicitation process of NUREG 1150 is provided and the elicitation of probabilities for the interfacing systems loss of coolant accident LOCA (ISL) in PWRs is given as an example of this elicitation process. Some lessons learned from this study are presented. (DG)

  4. Vaccination elicits a prominent acute phase response in horses.

    Science.gov (United States)

    Andersen, Susanne A; Petersen, Henrik H; Ersbøll, Annette K; Falk-Rønne, Jørgen; Jacobsen, Stine

    2012-02-01

    European and American guidelines for vaccination against tetanus and influenza in horses recommend annual and annual/semi-annual vaccinations, respectively, against the two pathogens. Too-frequent vaccination may, however, have adverse effects, among other things because an inflammatory response is elicited with subsequent alterations in homeostasis. The objective of the study was to compare the acute phase response (APR) in 10 horses following administration of two different types of vaccines, namely, an inactivated Immune Stimulating COMplex (ISCOM) vaccine and a live recombinant vector vaccine. Blood was sampled before and after vaccination to measure levels of serum amyloid A (SAA), fibrinogen, white blood cell counts (WBC) and iron. Vaccination induced a prominent APR with increased WBC, elevated blood levels of SAA and fibrinogen, and decreased serum iron concentrations. The ISCOM vaccine caused significantly (Phorse owners about convalescence after vaccination. Copyright © 2011 Elsevier Ltd. All rights reserved.

  5. Elicitation: A Tool for Enriching the Bioactive Composition of Foods

    Directory of Open Access Journals (Sweden)

    Nieves Baenas

    2014-09-01

    Full Text Available Elicitation is a good strategy to induce physiological changes and stimulate defense or stress-induced responses in plants. The elicitor treatments trigger the synthesis of phytochemical compounds in fruits, vegetables and herbs. These metabolites have been widely investigated as bioactive compounds responsible of plant cell adaptation to the environment, specific organoleptic properties of foods, and protective effects in human cells against oxidative processes in the development of neurodegenerative and cardiovascular diseases and certain types of cancer. Biotic (biological origin, abiotic (chemical or physical origin elicitors and phytohormones have been applied alone or in combinations, in hydroponic solutions or sprays, and in different selected time points of the plant growth or during post-harvest. Understanding how plant tissues and their specific secondary metabolic pathways respond to specific treatments with elicitors would be the basis for designing protocols to enhance the production of secondary metabolites, in order to produce quality and healthy fresh foods.

  6. Elicitation: a tool for enriching the bioactive composition of foods.

    Science.gov (United States)

    Baenas, Nieves; García-Viguera, Cristina; Moreno, Diego A

    2014-09-01

    Elicitation is a good strategy to induce physiological changes and stimulate defense or stress-induced responses in plants. The elicitor treatments trigger the synthesis of phytochemical compounds in fruits, vegetables and herbs. These metabolites have been widely investigated as bioactive compounds responsible of plant cell adaptation to the environment, specific organoleptic properties of foods, and protective effects in human cells against oxidative processes in the development of neurodegenerative and cardiovascular diseases and certain types of cancer. Biotic (biological origin), abiotic (chemical or physical origin) elicitors and phytohormones have been applied alone or in combinations, in hydroponic solutions or sprays, and in different selected time points of the plant growth or during post-harvest. Understanding how plant tissues and their specific secondary metabolic pathways respond to specific treatments with elicitors would be the basis for designing protocols to enhance the production of secondary metabolites, in order to produce quality and healthy fresh foods.

  7. Picture book exposure elicits positive visual preferences in toddlers.

    Science.gov (United States)

    Houston-Price, Carmel; Burton, Eliza; Hickinson, Rachel; Inett, Jade; Moore, Emma; Salmon, Katherine; Shiba, Paula

    2009-09-01

    Although the relationship between "mere exposure" and attitude enhancement is well established in the adult domain, there has been little similar work with children. This article examines whether toddlers' visual attention toward pictures of foods can be enhanced by repeated visual exposure to pictures of foods in a parent-administered picture book. We describe three studies that explored the number and nature of exposures required to elicit positive visual preferences for stimuli and the extent to which induced preferences generalize to other similar items. Results show that positive preferences for stimuli are easily and reliably induced in children and, importantly, that this effect of exposure is not restricted to the exposed stimulus per se but also applies to new representations of the exposed item.

  8. Fuzzy rationality and parameter elicitation in decision analysis

    Science.gov (United States)

    Nikolova, Natalia D.; Tenekedjiev, Kiril I.

    2010-07-01

    It is widely recognised by decision analysts that real decision-makers always make estimates in an interval form. An overview of techniques to find an optimal alternative among such with imprecise and interval probabilities is presented. Scalarisation methods are outlined as most appropriate. A proper continuation of such techniques is fuzzy rational (FR) decision analysis. A detailed representation of the elicitation process influenced by fuzzy rationality is given. The interval character of probabilities leads to the introduction of ribbon functions, whose general form and special cases are compared with the p-boxes. As demonstrated, approximation of utilities in FR decision analysis does not depend on the probabilities, but the approximation of probabilities is dependent on preferences.

  9. Eliciting design patterns for e-learning systems

    Science.gov (United States)

    Retalis, Symeon; Georgiakakis, Petros; Dimitriadis, Yannis

    2006-06-01

    Design pattern creation, especially in the e-learning domain, is a highly complex process that has not been sufficiently studied and formalized. In this paper, we propose a systematic pattern development cycle, whose most important aspects focus on reverse engineering of existing systems in order to elicit features that are cross-validated through the use of appropriate, authentic scenarios. However, an iterative pattern process is proposed that takes advantage of multiple data sources, thus emphasizing a holistic view of the teaching learning processes. The proposed schema of pattern mining has been extensively validated for Asynchronous Network Supported Collaborative Learning (ANSCL) systems, as well as for other types of tools in a variety of scenarios, with promising results.

  10. Promoting environmental sustainability via an expert elicitation process

    International Nuclear Information System (INIS)

    Swor, Tom; Canter, Larry

    2011-01-01

    Environmental sustainability (ES) planning was applied to the 981-mile, commercially navigable Ohio River. Navigation improvement needs were identified within the broad study along with actions to restore aquatic and riparian ecological resources to a higher state of sustainability. The actions were identified via an Expert Elicitation Process (EEP) involving aquatic and riparian/terrestrial experts knowledgeable of Ohio River resources. The received information was synthesized into goals for the selected resources (Valued Ecosystem Components - or VECs), actions or measures to attain the goals, and monitoring to evaluate conditions. Finally, 26 types of ES actions were identified and classified into three ES alternatives. These alternatives were then evaluated relative to key decision criteria, and such evaluations, based on pertinent decision criteria, were also conducted for four navigation improvement alternatives. Finally, the best combination of ES and navigation alternatives was identified. The key lessons derived from this use of EEP were that: (1) EEP can support the preliminary identification of ES measures; however, more detailed study of specific designs and cost evaluations will be necessary; (2) the method promotes collaboration between key scientists and policymakers from governmental agencies and private sectors, and such collaboration will ultimately provide the foundation for implementation of sustainability actions; and (3) an effective EEP does not occur by accident, it requires careful planning, implementation, and documentation. - Research Highlights: → Use of an Expert Elicitation Process (EEP) is demonstrated in this study. → EEP was used to identify Environmental Sustainability (ES) needs for the Ohio River. → EEP helped develop consensus among resource experts on ES needs. → EEP promotes collaboration to identify and contribute to common resource goals. → EEP may be used in assessing cumulative effects and formulating restoration

  11. Eliciting regret improves decision making at the end of life.

    Science.gov (United States)

    Djulbegovic, Benjamin; Tsalatsanis, Athanasios; Mhaskar, Rahul; Hozo, Iztok; Miladinovic, Branko; Tuch, Howard

    2016-11-01

    Management choices at the end of life are high-stake decisions fraught with emotions, chief among is regret. Our objective in this paper is to test the utility of a regret-based model to facilitate referral to hospice care while helping patients clarify their preferences on how they wish to spend the remaining days of their lives. A prospective cohort study that enrolled consecutive adult patients (n = 178) aware of the terminal nature of their disease. The patients were at the point in care where they had to decide between continuing potentially 'curative/life-prolonging' treatment (Rx) versus hospice care. Preferences were elicited using a Dual Visual Analog Scale regarding the level of regret of omission versus commission (RgO/RgC) towards hospice care and Rx. Each patient's RgO/RgC was contrasted against the predictive probability of death to suggest a management plan, which was then compared with the patient's actual choice. The probability of death was estimated using validated Palliative Performance Scale predictive model. Eighty-five percent (151/178) of patients agreed with the model's recommendations (p < 0.000001). Model predicted the actual choices for 72% (128/178) of patients (p < 0.00001). Logistic regression analysis showed that people who were initially inclined to be referred to hospice and were predicted to choose hospice over disease-directed treatment by the regret model have close to 98% probability of choosing hospice care at the end of their lives. No other factors (age, gender, race, educational status and pain level) affected their choice. Using regret to elicit choices in the end-of-life setting is both descriptively and prescriptively valid. People with terminal disease who are initially inclined to choose hospice and do not regret such a choice will select hospice care with high level of certainty. Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  12. The Lectin Domain of the Polypeptide GalNAc Transferase Family of Glycosyltransferases (ppGalNAc Ts) Acts as a Switch Directing Glycopeptide Substrate Glycosylation in an N- or C-terminal Direction, Further Controlling Mucin Type O-Glycosylation

    DEFF Research Database (Denmark)

    Gerken, Thomas A; Revoredo, Leslie; Thome, Joseph J C

    2013-01-01

    and specificity that differ between transferase isoforms. For example, ppGalNAc T1, T2, and T14 prefer C-terminally placed GalNAc-O-Thr, whereas ppGalNAc T3 and T6 prefer N-terminally placed GalNAc-O-Thr. Several transferase isoforms, ppGalNAc T5, T13, and T16, display equally enhanced N- or C-terminal activities...... relative to the nonglycosylated control peptides. This N- and/or C-terminal selectivity is presumably due to weak glycopeptide binding to the lectin domain, whose orientation relative to the catalytic domain is dynamic and isoform-dependent. Such N- or C-terminal glycopeptide selectivity provides...

  13. TRAC-Monterey FY16 Work Program Development and Report of Research Elicitation

    Science.gov (United States)

    2016-01-01

    any changes to priorities or additional projects that require immediate research. Work Program; Research Elicitation Unclassified UU UU UU UU 35 MAJ...conduct analysis for the Army. 1 Marks, Chris, Nesbitt, Peter. TRAC FY14 Research Requirements Elicitation . Technical Report TRAC-M-TM-13-059. 700 Dyer... Requirements Elicitation Interviews Interview Guide: 1. Describe a research requirement in the areas of topics, techniques, and methodologies. 2

  14. Application and Evaluation of an Expert Judgment Elicitation Procedure for Correlations.

    Science.gov (United States)

    Zondervan-Zwijnenburg, Mariëlle; van de Schoot-Hubeek, Wenneke; Lek, Kimberley; Hoijtink, Herbert; van de Schoot, Rens

    2017-01-01

    The purpose of the current study was to apply and evaluate a procedure to elicit expert judgments about correlations, and to update this information with empirical data. The result is a face-to-face group elicitation procedure with as its central element a trial roulette question that elicits experts' judgments expressed as distributions. During the elicitation procedure, a concordance probability question was used to provide feedback to the experts on their judgments. We evaluated the elicitation procedure in terms of validity and reliability by means of an application with a small sample of experts. Validity means that the elicited distributions accurately represent the experts' judgments. Reliability concerns the consistency of the elicited judgments over time. Four behavioral scientists provided their judgments with respect to the correlation between cognitive potential and academic performance for two separate populations enrolled at a specific school in the Netherlands that provides special education to youth with severe behavioral problems: youth with autism spectrum disorder (ASD), and youth with diagnoses other than ASD. Measures of face-validity, feasibility, convergent validity, coherence, and intra-rater reliability showed promising results. Furthermore, the current study illustrates the use of the elicitation procedure and elicited distributions in a social science application. The elicited distributions were used as a prior for the correlation, and updated with data for both populations collected at the school of interest. The current study shows that the newly developed elicitation procedure combining the trial roulette method with the elicitation of correlations is a promising tool, and that the results of the procedure are useful as prior information in a Bayesian analysis.

  15. Explaining choice option attractiveness by beliefs elicited by the laddering method

    DEFF Research Database (Denmark)

    Grunert, Klaus G.; Bech-Larsen, Tino

    2005-01-01

    option. The laddering method is used to elicit beliefs of all three types for a choice between conventional and organic pork. As a benchmark, beliefs were also elicited in the traditional way advocated by Ajzen and Fishbein. Using both sets of beliefs in a subsequent survey, it was shown that the beliefs...... elicited by the laddering method increase explanatory power with regard to choice option attractiveness beyond the beliefs elicited by the Ajzen and Fishbein method, and that this additional explanatory power was due to those beliefs which relate the choice option to concepts with a higher level...

  16. Eliciting Parents' Individual Requirements for an Inclusive Digital School System.

    Science.gov (United States)

    Eftring, Håkan; Rassmus-Gröhn, Kirsten; Hedvall, Per-Olof

    2016-01-01

    Parents often have a busy time sorting out their life puzzles, including getting information about their children's activities in school. More and more communication between teachers and parents take place via digital school systems. It can be hard for parents to find the information they are looking for and the teacher decides when information is sent and what communication method to use. All parents, but especially parents with disabilities, might have individual preferences on how to receive information and how to adapt meetings at school. In this paper we present a project where we involved parents and teachers in focus groups, an idea workshop and iterative user trials of a digital prototype. The goal was to elicit parents' individual requirements for an inclusive digital school system, where they can store their individual preferences about how and when to receive information from school and what requirements they have on meetings at school. Preliminary results show that we managed to create open and focused discussions among parents and teachers. The parents reacted very positively on an onboarding page with the possibility to quickly and easily enter preferences after their first log in, but more work needs to be done on how preferences are categorized on the onboarding page. Finally, parents need to get clear feedback from teachers and school when they have entered or updated preferences, so they can trust that their preferences will be met.

  17. Eliciting population preferences for mass colorectal cancer screening organization.

    Science.gov (United States)

    Nayaradou, Maximilien; Berchi, Célia; Dejardin, Olivier; Launoy, Guy

    2010-01-01

    The implementation of mass colorectal cancer (CRC) screening is a public health priority. Population participation is fundamental for the success of CRC screening as for any cancer screening program. The preferences of the population may influence their likelihood of participation. The authors sought to elicit population preferences for CRC screening test characteristics to improve the design of CRC screening campaigns. A discrete choice experiment was used. Questionnaires were compiled with a set of pairs of hypothetical CRC screening scenarios. The survey was conducted by mail from June 2006 to October 2006 on a representative sample of 2000 inhabitants, aged 50 to 74 years from the northwest of France, who were randomly selected from electoral lists. Questionnaires were sent to 2000 individuals, each of whom made 3 or 4 discrete choices between hypothetical tests that differed in 7 attributes: how screening is offered, process, sensitivity, rate of unnecessary colonoscopy, expected mortality reduction, method of screening test result transmission, and cost. Complete responses were received from 656 individuals (32.8%). The attributes that influenced population preferences included expected mortality reduction, sensitivity, cost, and process. Participants from high social classes were particularly influenced by sensitivity. The results demonstrate that the discrete choice experiment provides information on patient preferences for CRC screening: improving screening program effectiveness, for instance, by improving test sensitivity (the most valued attribute) would increase satisfaction among the general population with regard to CRC screening programs. Additional studies are required to study how patient preferences actually affect adherence to regular screening programs.

  18. Assessing Mental Models of Emergencies Through Two Knowledge Elicitation Tasks.

    Science.gov (United States)

    Whitmer, Daphne E; Sims, Valerie K; Torres, Michael E

    2017-05-01

    The goals of this study were to assess the risk identification aspect of mental models using standard elicitation methods and how university campus alerts were related to these mental models. People fail to follow protective action recommendations in emergency warnings. Past research has yet to examine cognitive processes that influence emergency decision-making. Study 1 examined 2 years of emergency alerts distributed by a large southeastern university. In Study 2, participants listed emergencies in a thought-listing task. Study 3 measured participants' time to decide if a situation was an emergency. The university distributed the most alerts about an armed person, theft, and fire. In Study 2, participants most frequently listed fire, car accident, heart attack, and theft. In Study 3, participants quickly decided a bomb, murder, fire, tornado, and rape were emergencies. They most slowly decided that a suspicious package and identify theft were emergencies. Recent interaction with warnings was only somewhat related to participants' mental models of emergencies. Risk identification precedes decision-making and applying protective actions. Examining these characteristics of people's mental representations of emergencies is fundamental to further understand why some emergency warnings go ignored. Someone must believe a situation is serious to categorize it as an emergency before taking the protective action recommendations in an emergency warning. Present-day research must continue to examine the problem of people ignoring warning communication, as there are important cognitive factors that have not yet been explored until the present research.

  19. An oral microjet vaccination system elicits antibody production in rabbits.

    Science.gov (United States)

    Aran, Kiana; Chooljian, Marc; Paredes, Jacobo; Rafi, Mohammad; Lee, Kunwoo; Kim, Allison Y; An, Jeanny; Yau, Jennifer F; Chum, Helen; Conboy, Irina; Murthy, Niren; Liepmann, Dorian

    2017-03-08

    Noninvasive immunization technologies have the potential to revolutionize global health by providing easy-to-administer vaccines at low cost, enabling mass immunizations during pandemics. Existing technologies such as transdermal microneedles are costly, deliver drugs slowly, and cannot generate mucosal immunity, which is important for optimal immunity against pathogens. We present a needle-free microjet immunization device termed MucoJet, which is a three-dimensional microelectromechanical systems-based drug delivery technology. MucoJet is administered orally, placed adjacent to the buccal tissue within the oral cavity, and uses a self-contained gas-generating chemical reaction within its two-compartment plastic housing to produce a high-pressure liquid jet of vaccine. We show that the vaccine jet ejected from the MucoJet device is capable of penetrating the buccal mucosal layer in silico, in porcine buccal tissue ex vivo, and in rabbits in vivo. Rabbits treated with ovalbumin by MucoJet delivery have antibody titers of anti-ovalbumin immunoglobulins G and A in blood serum and buccal tissue, respectively, that are three orders of magnitude higher than rabbits receiving free ovalbumin delivered topically by a dropper in the buccal region. MucoJet has the potential to accelerate the development of noninvasive oral vaccines, given its ability to elicit antibody production that is detectable locally in the buccal tissue and systemically via the circulation. Copyright © 2017, American Association for the Advancement of Science.

  20. Affective monitoring: A generic mechanism for affect elicitation

    Directory of Open Access Journals (Sweden)

    Hans ePhaf

    2012-03-01

    Full Text Available In this paper we sketch a new framework for affect elicitation, which is based on previous evolutionary and connectionist modeling and experimental work from our group. Affective monitoring is considered a local match-mismatch process within a module of the neural network. Negative affect is raised instantly by mismatches, incongruency, disfluency, novelty, incoherence, and dissonance, whereas positive affect follows from matches, congruency, fluency, familiarity, coherence, and resonance, at least when an initial mismatch can be solved quickly. Affective monitoring is considered an evolutionary-early conflict and change detection process operating at the same level as, for instance, attentional selection. It runs in parallel and imparts affective flavour to emotional behavior systems, which involve evolutionary-prepared stimuli and action tendencies related to for instance defensive, exploratory, attachment, or appetitive behavior. Positive affect is represented in the networks by high-frequency oscillations, presumably in the gamma band. Negative affect corresponds to more incoherent lower-frequency oscillations, presumably in the theta band. For affect to become conscious, large-scale synchronization of the oscillations over the network and the construction of emotional experiences are required. These constructions involve perceptions of bodily states and action tendencies, but also appraisals as well as efforts to regulate the emotion. Importantly, affective monitoring accompanies every kind of information processing, but conscious emotions, which result from the later integration of affect in a cognitive context, are much rarer events.

  1. Towards a framework for the elicitation of dilemmas.

    Science.gov (United States)

    Burger, Marc J C

    2008-08-01

    This paper covers the main findings of the doctoral research that was concerned with seeking to extend aspects of dilemma theory. In professional practice, the Trompenaars Hampden-Turner Dilemma Reconciliation Process(TM) is a vehicle delivering dilemma theory in application. It informs a manager or leader on how to explore the dilemmas they face, how to reconcile the tensions that result, and how to structure the action steps for implementing the reconciled solutions. This vehicle forms the professional practice of the author who seeks to bring more rigor to consulting practice and thereby also contribute to theory development in the domain. The critical review of dilemma theory reveals that previous authors are inconsistent and variously invalid in their use of the terms 'dilemma theory,' 'dilemma methodology,' 'dilemma process,' 'dilemma reconciliation,' etc., and therefore an attempt is made to resolve these inconsistencies by considering whether 'dilemmaism' at the meta-level might be positioned as a new paradigm of inquiry for (management) research that embodies ontological, epistemological, and methodical premises that frame an approach to the resolution of real world business problems in (multi) disciplinary; (multi) functional and (multi) cultural business environments. This research offers contributions to knowledge, professional practice and theory development from the exploration of the SPID model as a way to make the elicitation of dilemmas more rigorous and structured and in the broader context of exploring 'dilemmaism' as a new paradigm of inquiry.

  2. A sunny future: expert elicitation of China's solar photovoltaic technologies

    Science.gov (United States)

    Lam, Long T.; Branstetter, Lee; Azevedo, Inês L.

    2018-03-01

    China has emerged as the global manufacturing center for solar photovoltaic (PV) products. Chinese firms have entered all stages of the supply chain, producing most of the installed solar modules around the world. Meanwhile, production costs are at record lows. The decisions that Chinese solar producers make today will influence the path for the solar industry and its role towards de-carbonization of global energy systems in the years to come. However, to date, there have been no assessments of the future costs and efficiency of solar PV systems produced by the Chinese PV industry. We perform an expert elicitation to assess the technological and non-technological factors that led to the success of China’s silicon PV industry as well as likely future costs and performance. Experts evaluated key metrics such as efficiency, costs, and commercial viability of 17 silicon and non-silicon solar PV technologies by 2030. Silicon-based technologies will continue to be the mainstream product for large-scale electricity generation application in the near future, with module efficiency reaching as high as 23% and production cost as low as 0.24/W. The levelized cost of electricity for solar will be around 34/MWh, allowing solar PV to be competitive with traditional energy resources like coal. The industry’s future developments may be affected by overinvestment, overcapacity, and singular short-term focus.

  3. PEGylated graphene oxide elicits strong immunological responses despite surface passivation

    Science.gov (United States)

    Luo, Nana; Weber, Jeffrey K.; Wang, Shuang; Luan, Binquan; Yue, Hua; Xi, Xiaobo; Du, Jing; Yang, Zaixing; Wei, Wei; Zhou, Ruhong; Ma, Guanghui

    2017-02-01

    Engineered nanomaterials promise to transform medicine at the bio-nano interface. However, it is important to elucidate how synthetic nanomaterials interact with critical biological systems before such products can be safely utilized in humans. Past evidence suggests that polyethylene glycol-functionalized (PEGylated) nanomaterials are largely biocompatible and elicit less dramatic immune responses than their pristine counterparts. We here report results that contradict these findings. We find that PEGylated graphene oxide nanosheets (nGO-PEGs) stimulate potent cytokine responses in peritoneal macrophages, despite not being internalized. Atomistic molecular dynamics simulations support a mechanism by which nGO-PEGs preferentially adsorb onto and/or partially insert into cell membranes, thereby amplifying interactions with stimulatory surface receptors. Further experiments demonstrate that nGO-PEG indeed provokes cytokine secretion by enhancing integrin β8-related signalling pathways. The present results inform that surface passivation does not always prevent immunological reactions to 2D nanomaterials but also suggest applications for PEGylated nanomaterials wherein immune stimulation is desired.

  4. Genuine eye contact elicits self-referential processing.

    Science.gov (United States)

    Hietanen, Jonne O; Hietanen, Jari K

    2017-05-01

    The effect of eye contact on self-awareness was investigated with implicit measures based on the use of first-person singular pronouns in sentences. The measures were proposed to tap into self-referential processing, that is, information processing associated with self-awareness. In addition, participants filled in a questionnaire measuring explicit self-awareness. In Experiment 1, the stimulus was a video clip showing another person and, in Experiment 2, the stimulus was a live person. In both experiments, participants were divided into two groups and presented with the stimulus person either making eye contact or gazing downward, depending on the group assignment. During the task, the gaze stimulus was presented before each trial of the pronoun-selection task. Eye contact was found to increase the use of first-person pronouns, but only when participants were facing a real person, not when they were looking at a video of a person. No difference in self-reported self-awareness was found between the two gaze direction groups in either experiment. The results indicate that eye contact elicits self-referential processing, but the effect may be stronger, or possibly limited to, live interaction. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. When Do Morally Motivated Innovators Elicit Inspiration Instead of Irritation?

    Science.gov (United States)

    Bolderdijk, Jan Willem; Brouwer, Claire; Cornelissen, Gert

    2017-01-01

    Innovators (i.e., consumers who are the first to adopt an innovation) are pivotal for the societal diffusion of sustainable innovations. But when are innovators most influential? Recent work suggests that morally motivated innovators (i.e., consumers who adopt an innovation out of concern for the welfare of others) can make fellow consumers who have not yet adopted that innovation feel morally inadequate. As a self-defense mechanism, those fellow consumers might dismiss these innovators and their choices. As a result, ironically, morally motivated innovators might discourage others to adopt sustainable innovations. In an experimental study, we replicate this pattern, but also show that moral innovators can elicit a more positive response as well. Specifically, our results offer initial evidence that morally motivated innovators may be more inspiring than self-interested innovators, provided that their actions do not directly pose a threat to the moral self-concept of observers. In sum, our research sheds empirical light on the conditions under which innovators are likely to facilitate, rather than slow down the transition to a more sustainable society.

  6. Mechanism of phosphaturia elicited by administration of phosphonoformate in vivo

    International Nuclear Information System (INIS)

    VanScoy, M.; Loghman-Adham, M.; Onsgard, M.; Szczepanska-Konkel, M.; Homma, Sumiko; Knox, F.G.; Dousa, T.P.

    1988-01-01

    The authors examined whether phosphonoformate (PFA) can cause phosphaturia through its direct action on brush-border membrane (BBM) in vivo. Infusion of PFA or of parathyroid hormone (PTH) to thyroparathyroidectomized rats caused a marked increase in fractional excretion of phosphate without changes in excretion of Na + or of GFR. The PFA-induced phosphaturia was not accompanied by an increase in urinary adenosine-3',5'-cyclic monophosphate (cAMP); moreover, PFA added in vitro did not influence the PTH-sensitive adenylate cyclase and cAMP-phosphodiesterase in proximal convoluted tubules. In BBM vesicles (BBMV) from rats with PFA-elicited phosphaturia, neither the rate of Na + -P i symport nor Na + -dependent binding of [ 14 C]PFA on BBMV was changed, whereas in BBMV from PTH-infused rats the V max of Na + -P i symport decreased. PFA is almost completely ultrafiltrable; no metabolic transformation of PFA was detected after [ 14 C]PFA exposure to rat renal cortical slices, homogenate, or to blood. They conclude that PFA causes phosphaturia by direct inhibition of Na + -P i symport across BBM in proximal tubules, acting from the luminal side. Thus PFA (foscarnet) has a unique direct mechanism of phosphaturic effect, via its action on P i reabsorption in proximal tubules in vivo

  7. Impact of discussion on preferences elicited in a group setting

    Directory of Open Access Journals (Sweden)

    Milne Ruairidh

    2006-03-01

    Full Text Available Abstract Background The completeness of preferences is assumed as one of the axioms of expected utility theory but has been subject to little empirical study. Methods Fifteen non-health professionals was recruited and familiarised with the standard gamble technique. The group then met five times over six months and preferences were elicited independently on 41 scenarios. After individual valuation, the group discussed the scenarios, following which preferences could be changed. Changes made were described and summary measures (mean and median before and after discussion compared using paired t test and Wilcoxon Signed Rank Test. Semi-structured telephone interviews were carried out to explore attitudes to discussing preferences. These were transcribed, read by two investigators and emergent themes described. Results Sixteen changes (3.6% were made to preferences by seven (47% of the fifteen members. The difference between individual preference values before and after discussion ranged from -0.025 to 0.45. The average effect on the group mean was 0.0053. No differences before and after discussion were statistically significant. The group valued discussion highly and suggested it brought four main benefits: reassurance; improved procedural performance; increased group cohesion; satisfying curiosity. Conclusion The hypothesis that preferences are incomplete cannot be rejected for a proportion of respondents. However, brief discussion did not result in substantial number of changes to preferences and these did not have significant impact on summary values for the group, suggesting that incompleteness, if present, may not have an important effect on cost-utility analyses.

  8. Stone Soup: Photo-Elicitation as a Learning Tool in the Food Geography Classroom

    Science.gov (United States)

    Kurtz, Hilda E.; Wood, Jason

    2014-01-01

    This paper showcases self-reflective and inclusive pedagogy using photo-elicitation in a food geography course assignment. The Stone Soup project positions students as both researchers and participant-subjects in a participant-driven photo-elicitation (PDPE) study of students' foodways. Student papers for this assignment demonstrate rich…

  9. Photo-Elicitation and Visual Semiotics: A Unique Methodology for Studying Inclusion for Children with Disabilities

    Science.gov (United States)

    Stockall, Nancy

    2013-01-01

    The methodology in this paper discusses the use of photographs as an elicitation strategy that can reveal the thinking processes of participants in a qualitatively rich manner. Photo-elicitation techniques combined with a Piercian semiotic perspective offer a unique method for creating a frame of action for later participant analysis. Illustrative…

  10. Salient Beliefs in Majoring in Management Information Systems: An Elicitation Study

    Science.gov (United States)

    Chipidza, Wallace; Green, Gina; Riemenschneider, Cindy

    2016-01-01

    Research utilizing the Theory of Planned Behavior to understand behavior should first elicit beliefs about the phenomenon from the target population. In order to understand the reasons why students choose to major or not major in Management Information Systems (MIS), we elicited beliefs from 136 students attending university in the United States…

  11. Comparison of elicitation potential of chloroatranol and atranol - 2 allergens in oak moss absolute

    DEFF Research Database (Denmark)

    Johansen, J.D.; Bernard, G.; Gimenez-Arnau, E.

    2006-01-01

    of chloroatranol relative to atranol based on testing with equimolar concentrations was 217% (95% confidence interval 116-409%). Both substances elicited reactions at very low levels of exposure. It is concluded that the differences in elicitation capacity between the 2 substances are counterbalanced by exposure...

  12. Identifying and Responding to Personal Stressors: Utilizing Photo Elicitation in Health Education Courses

    Science.gov (United States)

    Hunter, Theresa

    2014-01-01

    The "Photo Elicitation Project" teaching idea applies the techniques of photo elicitation to stress prevention and management. This activity is designed to help students identify their personal stressors and to determine which stress prevention strategies are most useful for them. Objectives: students will be able to (a) identify current…

  13. Belief Elicitation to Populate Health Economic Models of Medical Diagnostic Devices in Development

    NARCIS (Netherlands)

    Haakma, Wieke; Steuten, Lotte Maria Gertruda; Bojke, Laura; IJzerman, Maarten Joost

    2014-01-01

    Background and Objective Bayesian methods can be used to elicit experts’ beliefs about the clinical value of healthcare technologies. This study investigates a belief–elicitation method for estimating diagnostic performance in an early stage of development of photoacoustic mammography (PAM) imaging

  14. Concurrent Data Elicitation Procedures, Processes, and the Early Stages of L2 Learning: A Critical Overview

    Science.gov (United States)

    Leow, Ronald P.; Grey, Sarah; Marijuan, Silvia; Moorman, Colleen

    2014-01-01

    Given the current methodological interest in eliciting direct data on the cognitive processes L2 learners employ as they interact with L2 data during the early stages of the learning process, this article takes a critical and comparative look at three concurrent data elicitation procedures currently employed in the SLA literature: Think aloud (TA)…

  15. Entropy-optimal weight constraint elicitation with additive multi-attribute utility models

    NARCIS (Netherlands)

    Valkenhoef , van Gert; Tervonen, Tommi

    2016-01-01

    We consider the elicitation of incomplete preference information for the additive utility model in terms of linear constraints on the weights. Eliciting incomplete preferences using holistic pair-wise judgments is convenient for the decision maker, but selecting the best pair-wise comparison is

  16. Eliciting and communicating expert judgments: methodology and application to nuclear safety

    International Nuclear Information System (INIS)

    Winterfeldt, D. von; Commission of the European Communities, Ispra

    1989-01-01

    Expert judgment has always been used informally in the analysis of complex engineering problems. Increasingly, however, the use of expert judgment has been formalized by eliciting judgments in an explicit, documented and often quantitative way. In nuclear safety studies the need for formal elicitation of expert judgments arises because of the lack of data and experiences, the need to adapt model results to the specific circumstances of a plant, and the large uncertainties surrounding the events and quantities that characterize an accident sequence. The recognition of the need for a formal elicitation of expert judgments has led to one of the most extensive expert elicitation processes to date in the context of the NUREG 1150 study. About 30 safety issues were quantified using expert judgments about probabilities of various uncertain events and quantities, ranging from the failure of a check valve in the cooling system to the pressure built up due to hydrogen production to release fractions of various radionuclides. In total, some 1000 probability distributions were elicited from some 50 experts. This paper first motivates the use of formal expert elicitation in complex engineering studies and describes the methodology of formal expert elicitation. Subsequently, it describes the overall approach of NUREG 1150 and provides an example of the elicitation of the probability of a bypass failure in a pressurized water reactor. The paper ends by discussing some lessons learned, problems encountered and by providing some recommendations

  17. Proposal for a Five-Step Method to Elicit Expert Judgment

    Directory of Open Access Journals (Sweden)

    Duco Veen

    2017-12-01

    Full Text Available Elicitation is a commonly used tool to extract viable information from experts. The information that is held by the expert is extracted and a probabilistic representation of this knowledge is constructed. A promising avenue in psychological research is to incorporated experts’ prior knowledge in the statistical analysis. Systematic reviews on elicitation literature however suggest that it might be inappropriate to directly obtain distributional representations from experts. The literature qualifies experts’ performance on estimating elements of a distribution as unsatisfactory, thus reliably specifying the essential elements of the parameters of interest in one elicitation step seems implausible. Providing feedback within the elicitation process can enhance the quality of the elicitation and interactive software can be used to facilitate the feedback. Therefore, we propose to decompose the elicitation procedure into smaller steps with adjustable outcomes. We represent the tacit knowledge of experts as a location parameter and their uncertainty concerning this knowledge by a scale and shape parameter. Using a feedback procedure, experts can accept the representation of their beliefs or adjust their input. We propose a Five-Step Method which consists of (1 Eliciting the location parameter using the trial roulette method. (2 Provide feedback on the location parameter and ask for confirmation or adjustment. (3 Elicit the scale and shape parameter. (4 Provide feedback on the scale and shape parameter and ask for confirmation or adjustment. (5 Use the elicited and calibrated probability distribution in a statistical analysis and update it with data or to compute a prior-data conflict within a Bayesian framework. User feasibility and internal validity for the Five-Step Method are investigated using three elicitation studies.

  18. What monitor can replace the cathode-ray tube for visual stimulation to elicit multifocal electroretinograms?

    Science.gov (United States)

    Matsumoto, Celso Soiti; Shinoda, Kei; Matsumoto, Harue; Seki, Keisuke; Nagasaka, Eiichiro; Iwata, Takeshi; Mizota, Atsushi

    2014-08-05

    To compare a conventional cathode-ray tube (CRT) screen to organic light-emitting diode (OLED) and liquid crystal display (LCD) screens as visual stimulators to elicit multifocal electroretinograms (mfERGs), mfERGs were recorded from seven eyes of seven healthy volunteers (21 ± 2 years). The mfERGs elicited by a conventional CRT screen (S710, Compaq Computer Co.) were compared to those elicited by a studio-grade master OLED monitor (PVM-1741, Sony, Japan) and a conventional LCD (S1721, Flexscan, Eizo Nanao Corp., Japan). The luminance changes of each monitor were measured with a photodiode. CRT, OLED, and LCD screens with a frame frequency of 60 Hz were studied. A hexagonal stimulus array with 61 stimulus elements was created on each monitor. The serial white stimuli of the OLED screen at 60 Hz did not fuse, and that of the LCD screens fused. The amplitudes of P1 and P2 of the first-order kernels of the mfERGs were not significantly different from those elicited by the CRT and OLED screens, and the P1 amplitude of the first-order kernel elicited by the LCD stimuli was significantly smaller than that elicited by the CRT in all the groups of the averaged hexagonal elements. The implicit times were approximately 10 ms longer in almost all components elicited by the LCD screen compared to those elicited by the CRT screen. The mfERGs elicited by monitors other than the CRT should be carefully interpreted, especially those elicited by LCD screens. The OLED had good performance, and we conclude that it can replace the CRT as a stimulator for mfERGs; however, a collection of normative data is recommended. © 2014 ARVO.

  19. Minocycline inhibits D-amphetamine-elicited action potential bursts in a central snail neuron.

    Science.gov (United States)

    Chen, Y-H; Lin, P-L; Wong, R-W; Wu, Y-T; Hsu, H-Y; Tsai, M-C; Lin, M-J; Hsu, Y-C; Lin, C-H

    2012-10-25

    Minocycline is a second-generation tetracycline that has been reported to have powerful neuroprotective properties. In our previous studies, we found that d-amphetamine (AMPH) elicited action potential bursts in an identifiable RP4 neuron of the African snail, Achatina fulica Ferussac. This study sought to determine the effects of minocycline on the AMPH-elicited action potential pattern changes in the central snail neuron, using the two-electrode voltage clamping method. Extracellular application of AMPH at 300 μM elicited action potential bursts in the RP4 neuron. Minocycline dose-dependently (300-900 μM) inhibited the action potential bursts elicited by AMPH. The inhibitory effects of minocycline on AMPH-elicited action potential bursts were restored by forskolin (50 μM), an adenylate cyclase activator, and by dibutyryl cAMP (N(6),2'-O-Dibutyryladenosine 3',5'-cyclic monophosphate; 1mM), a membrane-permeable cAMP analog. Co-administration of forskolin (50 μM) plus tetraethylammonium chloride (TEA; 5mM) or co-administration of TEA (5mM) plus dibutyryl cAMP (1mM) also elicited action potential bursts, which were prevented and inhibited by minocycline. In addition, minocycline prevented and inhibited forskolin (100 μM)-elicited action potential bursts. Notably, TEA (50mM)-elicited action potential bursts in the RP4 neuron were not affected by minocycline. Minocycline did not affect steady-state outward currents of the RP4 neuron. However, minocycline did decrease the AMPH-elicited steady-state current changes. Similarly, minocycline decreased the effects of forskolin-elicited steady-state current changes. Pretreatment with H89 (N-[2-(p-Bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide dihydrochloride; 10 μM), a protein kinase A inhibitor, inhibited AMPH-elicited action potential bursts and decreased AMPH-elicited steady-state current changes. These results suggest that the cAMP-protein kinase A signaling pathway and the steady-state current are involved in

  20. Video elicitation interviews: a qualitative research method for investigating physician-patient interactions.

    Science.gov (United States)

    Henry, Stephen G; Fetters, Michael D

    2012-01-01

    We describe the concept and method of video elicitation interviews and provide practical guidance for primary care researchers who want to use this qualitative method to investigate physician-patient interactions. During video elicitation interviews, researchers interview patients or physicians about a recent clinical interaction using a video recording of that interaction as an elicitation tool. Video elicitation is useful because it allows researchers to integrate data about the content of physician-patient interactions gained from video recordings with data about participants' associated thoughts, beliefs, and emotions gained from elicitation interviews. This method also facilitates investigation of specific events or moments during interactions. Video elicitation interviews are logistically demanding and time consuming, and they should be reserved for research questions that cannot be fully addressed using either standard interviews or video recordings in isolation. As many components of primary care fall into this category, high-quality video elicitation interviews can be an important method for understanding and improving physician-patient interactions in primary care.

  1. Video Elicitation Interviews: A Qualitative Research Method for Investigating Physician-Patient Interactions

    Science.gov (United States)

    Henry, Stephen G.; Fetters, Michael D.

    2012-01-01

    We describe the concept and method of video elicitation interviews and provide practical guidance for primary care researchers who want to use this qualitative method to investigate physician-patient interactions. During video elicitation interviews, researchers interview patients or physicians about a recent clinical interaction using a video recording of that interaction as an elicitation tool. Video elicitation is useful because it allows researchers to integrate data about the content of physician-patient interactions gained from video recordings with data about participants’ associated thoughts, beliefs, and emotions gained from elicitation interviews. This method also facilitates investigation of specific events or moments during interactions. Video elicitation interviews are logistically demanding and time consuming, and they should be reserved for research questions that cannot be fully addressed using either standard interviews or video recordings in isolation. As many components of primary care fall into this category, high-quality video elicitation interviews can be an important method for understanding and improving physician-patient interactions in primary care. PMID:22412003

  2. Eliciting Help Without Pity: The Effect of Changing Media Images on Perceptions of Disability.

    Science.gov (United States)

    Kamenetsky, Stuart B; Dimakos, Christina; Aslemand, Asal; Saleh, Amani; Ali-Mohammed, Saamiyah

    2016-01-01

    This study investigated whether newer, more positive disability charity images can elicit helping behavior without producing pity. One hundred sixty-one university undergraduate students were presented with 35 older (1960-1990) and newer (1991-2010) disability charity images and completed a questionnaire about each image. Results indicate that overall, identification with depicted individuals was low; positive attitudes and perceptions of capabilities were moderate to high. Newer images led to more positive responses, but no significant difference in willingness to help. Eliciting pity through negative depictions of disability appears not to be a necessary precondition for eliciting helping behavior toward people with disabilities.

  3. Attributes Of Quality Scenarios/Scenario Sets Used In Software Requirements Elicitation

    National Research Council Canada - National Science Library

    Braun, Kimberly

    1997-01-01

    .... This thesis examines scenarios used in software requirements elicitation. Many different definitions, formats, and ideas exist on scenarios, but no thorough work has been done on what makes a good, quality scenario and scenario set...

  4. Requirements model generation to support requirements elicitation: The Secure Tropos experience

    NARCIS (Netherlands)

    Kiyavitskaya, N.; Zannone, N.

    2008-01-01

    In recent years several efforts have been devoted by researchers in the Requirements Engineering community to the development of methodologies for supporting designers during requirements elicitation, modeling, and analysis. However, these methodologies often lack tool support to facilitate their

  5. Neuronal Activation in the Medulla Oblongata during Selective Elicitation of the Laryngeal Adductor Response

    Science.gov (United States)

    Ambalavanar, Ranjinidevi; Tanaka, Yasumasa; Selbie, W. Scott; Ludlow, Christy L.

    2008-01-01

    Swallow and cough are complex motor patterns elicited by rapid and intense electrical stimulation of the internal branch of the superior laryngeal nerve (ISLN). The laryngeal adductor response (LAR) includes only a laryngeal response, is elicited by single stimuli to the ISLN, and is thought to represent the brain stem pathway involved in laryngospasm. To identify which regions in the medulla are activated during elicitation of the LAR alone, single electrical stimuli were presented once every 2 s to the ISLN. Two groups of 5 cats each were studied; an experimental group with unilateral ISLN stimulation at 0.5 Hz and a surgical control group. Three additional cats were studied to evaluate whether other oral, pharyngeal or respiratory muscles were activated during ISLN stimulation eliciting LAR. We quantified up to 22 sections for each of 14 structures in the medulla to determine if regions had increased Fos-like immunoreactive neurons in the experimental group. Significant increases (p medulla. PMID:15212423

  6. Conditioning stimulation techniques for enhancement of transcranially elicited evoked motor responses

    NARCIS (Netherlands)

    Journee, H. -L.; Polak, H. E.; De Kleuver, M.

    2007-01-01

    Introduction. - In spite of the use of multipulse, transcranial electrical stimulation (TES) is still insufficient in a subgroup of patients to elicit motor-evoked potentials during intraoperative neurophysiological monitoring (IONM). Classic facilitation methods used in awake patients are precluded

  7. Eliciting Preferences of Multimorbid Elderly Adults in Family Practice Using an Outcome Prioritization Tool

    NARCIS (Netherlands)

    van Summeren, Jojanneke J. G. T.; Haaijer-Ruskamp, Flora M.; Schuling, Jan

    2016-01-01

    ObjectivesTo explore an outcome prioritization tool (OPT) in eliciting individuals' preferred health outcomes (remaining alive, maintaining independence, reducing pain, reducing other symptoms) in the context of medication review in family practice. DesignCross-sectional pilot study with

  8. A Systematic Review to Identify the Use of Preference Elicitation Methods in Healthcare Decision Making

    NARCIS (Netherlands)

    Weernink, Marieke Geertruida Maria; Janus, Sarah; van Til, Janine Astrid; Raisch, Dennis; van Manen, Jeanette Gabrielle; IJzerman, Maarten Joost

    2014-01-01

    Introduction: Preference elicitation methods help to increase patient-centred medical decision making (MDM) by measuring benefit and value. Preferences can be applied in decisions regarding reimbursement, including health technology assessment (HTA); market access, including benefit–risk assessment

  9. Knowledge acquisition in ecological poduct design: the effects of computer-mediated communication and elicitation method

    OpenAIRE

    Sauer, J.; Schramme, S.; Rüttinger, B.

    2000-01-01

    This article presents a study that examines multiple effects of using different means of computer-mediated communication and knowledge elicitation methods during a product design process. The experimental task involved a typical scenario in product design, in which a knowledge engineer consults two experts to generate knowledge about a design issue. Employing a 3x2 between-subjects design, three conference types (face-to-face, computer, multivedia) and two knowledge elicitation methods (struc...

  10. Periodic modulation of repetitively elicited monosynaptic reflexes of the human lumbosacral spinal cord

    OpenAIRE

    Hofstoetter, Ursula S.; Danner, Simon M.; Freundl, Brigitta; Binder, Heinrich; Mayr, Winfried; Rattay, Frank; Minassian, Karen

    2015-01-01

    In individuals with motor-complete spinal cord injury, epidural stimulation of the lumbosacral spinal cord at 2 Hz evokes unmodulated reflexes in the lower limbs, while stimulation at 22–60 Hz can generate rhythmic burstlike activity. Here we elaborated on an output pattern emerging at transitional stimulation frequencies with consecutively elicited reflexes alternating between large and small. We analyzed responses concomitantly elicited in thigh and leg muscle groups bilaterally by epidural...

  11. A new method for eliciting three speaking styles in the laboratory

    OpenAIRE

    Harnsberger, James D.; Wright, Richard; Pisoni, David B.

    2008-01-01

    In this study, a method was developed to elicit three different speaking styles, reduced, citation, and hyperarticulated, using controlled sentence materials in a laboratory setting. In the first set of experiments, the reduced style was elicited by having twelve talkers read a sentence while carrying out a distractor task that involved recalling from short-term memory an individually-calibrated number of digits. The citation style corresponded to read speech in the laboratory. The hyperartic...

  12. Evaluation of Antioxidant and Antibacterial Potentials of Nigella sativa L. Suspension Cultures under Elicitation

    Directory of Open Access Journals (Sweden)

    Hera Chaudhry

    2015-01-01

    Full Text Available Nigella sativa L. (family Ranunculaceae is an annual herb of immense medicinal properties because of its major active components (i.e., thymoquinone (TQ, thymohydroquinone (THQ, and thymol (THY. Plant tissue culture techniques like elicitation, Agrobacterium mediated transformation, hairy root culture, and so on, are applied for substantial metabolite production. This study enumerates the antibacterial and antioxidant potentials of N. sativa epicotyl suspension cultures under biotic and abiotic elicitation along with concentration optimization of the elicitors for enhanced TQ and THY production. Cultures under different concentrations of pectin and manganese chloride (MnCl2 elicitation (i.e., 5 mg/L, 10 mg/L, and 15 mg/L showed that the control, MnCl2 10 mg/L, and pectin 15 mg/L suspension extracts greatly inhibited the growth of E. coli, S. typhimurium, and S. aureus (MIC against E. coli, i.e., 2.35±0.8, 2.4±0.2, and 2.46±0.5, resp.. Elicitation decreased SOD enzyme activity whereas CAT enzyme activity increased remarkably under MnCl2 elicitation. MnCl2 10 mg/L and pectin 15 mg/L elicitation enhanced the DPPH radical inhibition ability, but ferric scavenging activity was comparable to the control. TQ and THY were quantified by LC-MS/MS in the cultures with high bioactive properties revealing maximum content under MnCl2 10 mg/L elicitation. Therefore, MnCl2 elicitation can be undertaken on large scale for sustainable metabolite production.

  13. Evaluation of Antioxidant and Antibacterial Potentials of Nigella sativa L. Suspension Cultures under Elicitation.

    Science.gov (United States)

    Chaudhry, Hera; Fatima, Nida; Ahmad, Iffat Zareen

    2015-01-01

    Nigella sativa L. (family Ranunculaceae) is an annual herb of immense medicinal properties because of its major active components (i.e., thymoquinone (TQ), thymohydroquinone (THQ), and thymol (THY)). Plant tissue culture techniques like elicitation, Agrobacterium mediated transformation, hairy root culture, and so on, are applied for substantial metabolite production. This study enumerates the antibacterial and antioxidant potentials of N. sativa epicotyl suspension cultures under biotic and abiotic elicitation along with concentration optimization of the elicitors for enhanced TQ and THY production. Cultures under different concentrations of pectin and manganese chloride (MnCl2) elicitation (i.e., 5 mg/L, 10 mg/L, and 15 mg/L) showed that the control, MnCl2 10 mg/L, and pectin 15 mg/L suspension extracts greatly inhibited the growth of E. coli, S. typhimurium, and S. aureus (MIC against E. coli, i.e., 2.35 ± 0.8, 2.4 ± 0.2, and 2.46 ± 0.5, resp.). Elicitation decreased SOD enzyme activity whereas CAT enzyme activity increased remarkably under MnCl2 elicitation. MnCl2 10 mg/L and pectin 15 mg/L elicitation enhanced the DPPH radical inhibition ability, but ferric scavenging activity was comparable to the control. TQ and THY were quantified by LC-MS/MS in the cultures with high bioactive properties revealing maximum content under MnCl2 10 mg/L elicitation. Therefore, MnCl2 elicitation can be undertaken on large scale for sustainable metabolite production.

  14. Persuasion Through Emotion? An Experimental Test of the Emotion-Eliciting Nature of Populist Communication

    OpenAIRE

    Wirz, Dominique

    2018-01-01

    Populist parties have been extremely successful in recent years. It is often argued that their focus on emotion-eliciting appeals instead of rational arguments contributes to this success; however, there is a lack of empirical evidence to support this assumption. The objective of this article is to test whether populist appeals do indeed elicit emotions and whether this increases the persuasiveness of the appeals. An experiment was conducted (N = 580) comparing populist and nonpopulist appeal...

  15. Functional Imaging of Human Vestibular Cortex Activity Elicited by Skull Tap and Auditory Tone Burst

    Science.gov (United States)

    Noohi, Fatemeh; Kinnaird, Catherine; Wood, Scott; Bloomberg, Jacob; Mulavara, Ajitkumar; Seidler, Rachael

    2014-01-01

    The aim of the current study was to characterize the brain activation in response to two modes of vestibular stimulation: skull tap and auditory tone burst. The auditory tone burst has been used in previous studies to elicit saccular Vestibular Evoked Myogenic Potentials (VEMP) (Colebatch & Halmagyi 1992; Colebatch et al. 1994). Some researchers have reported that airconducted skull tap elicits both saccular and utricle VEMPs, while being faster and less irritating for the subjects (Curthoys et al. 2009, Wackym et al., 2012). However, it is not clear whether the skull tap and auditory tone burst elicit the same pattern of cortical activity. Both forms of stimulation target the otolith response, which provides a measurement of vestibular function independent from semicircular canals. This is of high importance for studying the vestibular disorders related to otolith deficits. Previous imaging studies have documented activity in the anterior and posterior insula, superior temporal gyrus, inferior parietal lobule, pre and post central gyri, inferior frontal gyrus, and the anterior cingulate cortex in response to different modes of vestibular stimulation (Bottini et al., 1994; Dieterich et al., 2003; Emri et al., 2003; Schlindwein et al., 2008; Janzen et al., 2008). Here we hypothesized that the skull tap elicits the similar pattern of cortical activity as the auditory tone burst. Subjects put on a set of MR compatible skull tappers and headphones inside the 3T GE scanner, while lying in supine position, with eyes closed. All subjects received both forms of the stimulation, however, the order of stimulation with auditory tone burst and air-conducted skull tap was counterbalanced across subjects. Pneumatically powered skull tappers were placed bilaterally on the cheekbones. The vibration of the cheekbone was transmitted to the vestibular cortex, resulting in vestibular response (Halmagyi et al., 1995). Auditory tone bursts were also delivered for comparison. To validate

  16. Using process elicitation and validation to understand and improve chemotherapy ordering and delivery.

    Science.gov (United States)

    Mertens, Wilson C; Christov, Stefan C; Avrunin, George S; Clarke, Lori A; Osterweil, Leon J; Cassells, Lucinda J; Marquard, Jenna L

    2012-11-01

    Chemotherapy ordering and administration, in which errors have potentially severe consequences, was quantitatively and qualitatively evaluated by employing process formalism (or formal process definition), a technique derived from software engineering, to elicit and rigorously describe the process, after which validation techniques were applied to confirm the accuracy of the described process. The chemotherapy ordering and administration process, including exceptional situations and individuals' recognition of and responses to those situations, was elicited through informal, unstructured interviews with members of an interdisciplinary team. The process description (or process definition), written in a notation developed for software quality assessment purposes, guided process validation (which consisted of direct observations and semistructured interviews to confirm the elicited details for the treatment plan portion of the process). The overall process definition yielded 467 steps; 207 steps (44%) were dedicated to handling 59 exceptional situations. Validation yielded 82 unique process events (35 new expected but not yet described steps, 16 new exceptional situations, and 31 new steps in response to exceptional situations). Process participants actively altered the process as ambiguities and conflicts were discovered by the elicitation and validation components of the study. Chemotherapy error rates declined significantly during and after the project, which was conducted from October 2007 through August 2008. Each elicitation method and the subsequent validation discussions contributed uniquely to understanding the chemotherapy treatment plan review process, supporting rapid adoption of changes, improved communication regarding the process, and ensuing error reduction.

  17. Eliciting and Defining Requirements Based on Metaevaluation: the Case of the CRAS 2008 Census

    Directory of Open Access Journals (Sweden)

    Edilson Ferneda

    2014-10-01

    Full Text Available The Brazilian Ministry of Social Development and Fight against Hunger (MDS regularly promotes the evaluation of its social programs, such as those developed in the Reference Centers for Social Assistance (CRAS. Such evaluations make use of a web system that supports the collection and processing of information as well as the dissemination of its results to local, regional and central government officials through the so-called CRAS Census. A meta-evaluation of the CRAS 2008 Census was carried out based on criteria specified by the Joint Committee (1994, from which we elicited requirements that enabled improvements of the web system. The article reports new requirements elicited from the meta-evaluation of the CRAS 2008 Census, held in the period 2009-2010. The approach of meta-evaluation as an alternative source of requirements elicitation took into consideration results from evaluations of social programs in order to identify system problems without the usual need of intense interaction with users. This approach revealed opportunities for improvements in the evaluation process that led to the elicitation of requirements for the computerized system. Some of the elicited features were incorporated into the Census 2010 and others may be incorporated in future censuses.

  18. The capsaicin cough reflex in eczema patients with respiratory symptoms elicited by perfume

    DEFF Research Database (Denmark)

    Elberling, Jesper; Dirksen, Asger; Johansen, Jeanne Duus

    2006-01-01

    Respiratory symptoms elicited by perfume are common in the population but have unclear pathophysiology. Increased capsaicin cough responsiveness has been associated with the symptoms, but it is unknown whether the site of the symptoms in the airways influences this association. The aim of this st......Respiratory symptoms elicited by perfume are common in the population but have unclear pathophysiology. Increased capsaicin cough responsiveness has been associated with the symptoms, but it is unknown whether the site of the symptoms in the airways influences this association. The aim...... of this study was to investigate the association between the site of airway symptoms elicited by perfume and cough responsiveness to bronchial challenge with capsaicin. 21 eczema patients with respiratory symptoms elicited by perfume were compared with 21 healthy volunteers in a sex- and age-matched case...... control study. The participants completed a symptom questionnaire and underwent a bronchial challenge with capsaicin. Lower, but not upper, respiratory symptoms elicited by perfume were associated with increased capsaicin cough responsiveness. Having severe symptoms to perfume (n=11) did not relate...

  19. The capsaicin cough reflex in eczema patients with respiratory symptoms elicited by perfume.

    Science.gov (United States)

    Elberling, Jesper; Dirksen, Asger; Johansen, Jeanne Duus; Mosbech, Holger

    2006-03-01

    Respiratory symptoms elicited by perfume are common in the population but have unclear pathophysiology. Increased capsaicin cough responsiveness has been associated with the symptoms, but it is unknown whether the site of the symptoms in the airways influences this association. The aim of this study was to investigate the association between the site of airway symptoms elicited by perfume and cough responsiveness to bronchial challenge with capsaicin. 21 eczema patients with respiratory symptoms elicited by perfume were compared with 21 healthy volunteers in a sex- and age-matched case control study. The participants completed a symptom questionnaire and underwent a bronchial challenge with capsaicin. Lower, but not upper, respiratory symptoms elicited by perfume were associated with increased capsaicin cough responsiveness. Having severe symptoms to perfume (n=11) did not relate to the site of the symptoms in the airways and was not associated with increased capsaicin cough responsiveness. In conclusion, respiratory symptoms elicited by perfume may reflect local hyperreactivity related to defensive reflexes in the airways, and measurements of the capsaicin cough reflex are relevant when patients with lower respiratory symptoms related to environmental perfume exposures are investigated.

  20. 9-methoxycanthin-6-one production in elicited hairy roots culture of Eurycoma longifolia

    Science.gov (United States)

    Abdullah, Nazirah; Ismail, Ismanizan; Hassan, Nor Hasnida; Basherudin, Norlia

    2016-11-01

    Eurycoma longifolia (Tongkat Ali) is a highly sought after medicinal plant in Malaysia. Propagation of E. longifolia through tissue culture has been reported in order to cater the industry demands for planting and raw materials as well as for conservation purposes. E. longifolia hairy roots culture has been developed using Agrobacterium rhizogenes for the production of Tongkat Ali phytochemicals. Effects of three elicitors; methyl jasmonate, salicylic acid, and yeast extract at different concentrations were evaluated on the production of 9-methoxycanthin-6-one in E. longifolia hairy roots. The cultures were elicited at early exponential growth phase, followed by extraction of 9-methoxycanthin-6-one using methanol and HPLC analysis. Elicitation with methyl jasmonate at all concentrations increased 9-methoxycanthin-6-one up to 1-3 fold and treatment with (0.1 mM) was most efficient in enhancing 9-methoxycanthin-6-one production up to 3.902 mg/g dry weight after 7 days (168 hours) elicitation.

  1. Good Food, Bad Food, and White Rice: Understanding Child Feeding Using Visual-Narrative Elicitation.

    Science.gov (United States)

    Wentworth, Chelsea

    2017-01-01

    Visual-narrative elicitation, a process combining photo elicitation and pile sorting in applied medical anthropology, sheds light on food consumption patterns in urban areas of Vanuatu where childhood malnutrition is a persistent problem. Groups of participants took photographs of the foods they feed their children, and the resources and barriers they encounter in accessing foodstuffs. This revealed how imported and local foods are assigned value as "good" or "bad" foods when contributing to dietary diversity and creating appropriate meals for children, particularly in the context of consuming white rice. The process of gathering and working with photographs illuminated the complex negotiations in which caregivers engaged when making food and nutritional choices for their children. At the nexus of visual and medical anthropology, the visual-narrative elicitation process yielded nuanced, comprehensive understandings of how caregivers value the various foods they feed their children.

  2. "I Don't Know What's Right Anymore": Engaging Distressed Interviewees Using Graphic-Elicitation

    Directory of Open Access Journals (Sweden)

    Geoff Kuehne

    2013-07-01

    Full Text Available Graphic-elicitation appears to be a research method that potentially has much to offer, particularly so when working with distressed and disaffected groups. It can be especially suited to presenting contentious ideas with unwelcome implications to sceptical interviewees, in this case irrigation farmers who were questioning aspects of climate change. Five images were introduced in the course of conducting in-depth personal interviews. The interviews were recorded and analysed for recurrent themes related to the images. The graphic-elicitation method allowed some participants to preserve or build their sense of optimism by viewing the graphic-elicitation images in particular ways—they saw in them what they wanted to see. Encouraged by the images some attempted to transfer their felt responsibility toward climate change responses to the government and upstream irrigators by blaming them for their low water availability. URN: http://nbn-resolving.de/urn:nbn:de:0114-fqs130321

  3. Induction of phenolic compounds in Hypericum perforatum L. cells by Colletotrichum gloeosporioides elicitation.

    Science.gov (United States)

    Conceição, Luis F R; Ferreres, Federico; Tavares, Rui M; Dias, Alberto C P

    2006-01-01

    Changes in phenolic metabolism after elicitation with Colletotrichum gloeosporioides (CG) has been studied in Hypericum perforatum L. (HP) cell suspension cultures. Soluble phenolics were analysed by HPLC-DAD and HPLC-DAD-MS/MS. HP cultures elicited with the CG elicitor showed a significant increase in xanthone accumulation. Xanthone accumulation increased twelve fold when the cells were primed with methyl-jasmonate (MeJ) or salicylic acid (SA), before elicitation. HP cultures exposed only to MeJ produced a set of flavonoids, the flavones which represent a substantial part (approx. 40%) of the total flavonoids accumulated in these cells. The possible importance of xanthones as a component of defence mechanism of HP against biotic stress is discussed.

  4. Investigation of bias of hedonic scores when co-eliciting product attribute information using CATA questions

    DEFF Research Database (Denmark)

    Jaeger, Sara R.; Giacalone, Davide; Roigard, Cristina M.

    2013-01-01

    (appearance, aroma, flavour, taste, aftertaste, mouthfeel). The present research suggests that co-elicitation of hedonic scores and product attribute information using CATA questions may bias the hedonic scores, but not that it certainly will do so. This needs to be recognised, leading to more widespread......Sensory and consumer scientists disagree on the practice of concurrently obtaining sensory information in hedonic tests. This is in part due to different mindsets about what consumers are able to do and evidence that such co-elicitation may bias hedonic scores. Check-all-that-apply (CATA) questions...... have been claimed to have a smaller effect on hedonic scores than other attribute such as just-about-right or intensity scales. In this research, nine studies using consumers as participants examined effects on hedonic product scores when sensory attribute information was co-elicited using CATA...

  5. Engineered CAR T Cells Targeting the Cancer-Associated Tn-Glycoform of the Membrane Mucin MUC1 Control Adenocarcinoma

    DEFF Research Database (Denmark)

    Posey, Avery D; Schwab, Robert D; Boesteanu, Alina C

    2016-01-01

    with sufficient cancer-specific expression. The majority of CAR targets have been normal self-antigens on dispensable hematopoietic tissues or overexpressed shared antigens. Here, we established that abnormal self-antigens can serve as targets for tumor rejection. We developed a CAR that recognized cancer...

  6. 78 FR 11895 - Prospective Grant of Exclusive License: Development of MUC-1 Tumor Associated Antigens as Cancer...

    Science.gov (United States)

    2013-02-20

    ... recent approach where tumor associated antigens (TAAs), which are primarily expressed in human tumor cells, and not expressed or minimally expressed in normal tissues, are employed to generate a tumor... royalty bearing and will comply with the terms and conditions of 35 U.S.C. 209 and 37 CFR Part 404.7. The...

  7. Action potential bursts in central snail neurons elicited by paeonol: roles of ionic currents

    Science.gov (United States)

    Chen, Yi-hung; Lin, Pei-lin; Hsu, Hui-yu; Wu, Ya-ting; Yang, Han-yin; Lu, Dah-yuu; Huang, Shiang-suo; Hsieh, Ching-liang; Lin, Jaung-geng

    2010-01-01

    Aim: To investigate the effects of 2′-hydroxy-4′-methoxyacetophenone (paeonol) on the electrophysiological behavior of a central neuron (right parietal 4; RP4) of the giant African snail (Achatina fulica Ferussac). Methods: Intracellular recordings and the two-electrode voltage clamp method were used to study the effects of paeonol on the RP4 neuron. Results: The RP4 neuron generated spontaneous action potentials. Bath application of paeonol at a concentration of ≥500 μmol/L reversibly elicited action potential bursts in a concentration-dependent manner. Immersing the neurons in Co2+-substituted Ca2+-free solution did not block paeonol-elicited bursting. Pretreatment with the protein kinase A (PKA) inhibitor KT-5720 or the protein kinase C (PKC) inhibitor Ro 31-8220 did not affect the action potential bursts. Voltage-clamp studies revealed that paeonol at a concentration of 500 μmol/L had no remarkable effects on the total inward currents, whereas paeonol decreased the delayed rectifying K+ current (IKD) and the fast-inactivating K+ current (IA). Application of 4-aminopyridine (4-AP 5 mmol/L), an inhibitor of IA, or charybdotoxin 250 nmol/L, an inhibitor of the Ca2+-activated K+ current (IK(Ca)), failed to elicit action potential bursts, whereas tetraethylammonium chloride (TEA 50 mmol/L), an IKD blocker, successfully elicited action potential bursts. At a lower concentration of 5 mmol/L, TEA facilitated the induction of action potential bursts elicited by paeonol. Conclusion: Paeonol elicited a bursting firing pattern of action potentials in the RP4 neuron and this activity relates closely to the inhibitory effects of paeonol on the IKD. PMID:21042287

  8. Muscular reflexes elicited by electrical stimulation of the anterior cruciate ligament in humans

    DEFF Research Database (Denmark)

    Dyhre-Poulsen, P; Krogsgaard, M R

    2000-01-01

    no sign of ACL disease, thin wire electrodes were inserted into the proximal and mid parts of the ACL. Postoperatively, the sensory nerve fibers inside the ACL were stimulated electrically while motor activity in the knee muscles was recorded using electromyography. In seven of the eight patients......, a muscular contraction of the semitendinosus muscle could be elicited with stimulus trains consisting of at least two stimuli. The latency was 95 +/- 35 ms. Stimulation during isometric contraction of either extensor or flexor muscles elicited a short, complete inhibition of the muscle activity...

  9. Cue-elicited anxiety and craving for food using virtual reality scenarios.

    Science.gov (United States)

    Ferrer-García, Marta; Gutiérrez-Maldonado, José; Pla, Joana

    2013-01-01

    Cue exposure therapy has been reported to be an effective intervention for reducing binge eating behavior in patients with eating disorders and obesity. However, in vivo food exposure conducted in the therapist's office presents logistical problems and lacks ecological validity. This study proposes the use of virtual reality technology as an alternative to in vivo exposure, and assesses the ability of different virtual environments to elicit anxiety and craving for food in a non-clinical sample. The results show that exposure to virtual environments provokes changes in reported craving for food. High-calorie food cues are the ones that elicit the highest increases in craving.

  10. Impact of Requirements Elicitation Processes on Success of Information System Development Projects

    Directory of Open Access Journals (Sweden)

    Bormane Līga

    2016-12-01

    Full Text Available Requirements articulating user needs and corresponding to enterprise business processes are a key to successful implementation of information system development projects. However, the parties involved in projects frequently are not able to agree on a common development vision and have difficulties expressing their needs. Several industry experts have acknowledged that requirements elicitation is one of the most difficult tasks in development projects. This study investigates the impact of requirements elicitation processes on project outcomes depending on the applied project development methodology.

  11. Expert Elicitation Methods in Quantifying the Consequences of Acoustic Disturbance from Offshore Renewable Energy Developments.

    Science.gov (United States)

    Donovan, Carl; Harwood, John; King, Stephanie; Booth, Cormac; Caneco, Bruno; Walker, Cameron

    2016-01-01

    There are many developments for offshore renewable energy around the United Kingdom whose installation typically produces large amounts of far-reaching noise, potentially disturbing many marine mammals. The potential to affect the favorable conservation status of many species means extensive environmental impact assessment requirements for the licensing of such installation activities. Quantification of such complex risk problems is difficult and much of the key information is not readily available. Expert elicitation methods can be employed in such pressing cases. We describe the methodology used in an expert elicitation study conducted in the United Kingdom for combining expert opinions based on statistical distributions and copula-like methods.

  12. Research Synthesis Methods in an Age of Globalized Risks: Lessons from the Global Burden of Foodborne Disease Expert Elicitation

    DEFF Research Database (Denmark)

    Hald, Tine; Angulo, Fred; Bin Hamzah, Wan Mansor

    2016-01-01

    We live in an age that increasingly calls for national or regional management of global risks. This article discusses the contributions that expert elicitation can bring to efforts to manage global risks and identifies challenges faced in conducting expert elicitation at this scale. In doing so...... it draws on lessons learned from conducting an expert elicitation as part of the World Health Organizations (WHO) initiative to estimate the global burden of foodborne disease; a study commissioned by the Foodborne Disease Epidemiology Reference Group (FERG). Expert elicitation is designed to fill gaps...

  13. Deliberative Teacher Education beyond Boundaries: Discursive Practices for Eliciting Gender Awareness

    Science.gov (United States)

    Mooney Simmie, Geraldine; Lang, Manfred

    2018-01-01

    This study uses boundary crossing in activity theory as one normative framework for opening a deliberative inquiry in new discursive spaces to elicit "gender awareness" in teachers' practices. We illustrate this framework by drawing from data in one European teacher education project. Seven case studies were conducted and data were…

  14. The Time-Dose-Response Relationship for Elicitation of Contact Dermatitis in Isoeugenol Allergic Individuals

    DEFF Research Database (Denmark)

    Andersen, K. E.; Johansen, J. D.; Bruze, M.

    2001-01-01

    The elicitation response in allergic contact dermatitis is dose dependent, but the time-concentration relationship for elicitation has not previously been described. In this study 27 isoeugenol-sensitive patients participated in serial dilution patch tests with isoeugenol and a double-blinded Rep......The elicitation response in allergic contact dermatitis is dose dependent, but the time-concentration relationship for elicitation has not previously been described. In this study 27 isoeugenol-sensitive patients participated in serial dilution patch tests with isoeugenol and a double......-blinded Repeated Open Application Test (ROAT) using two concentrations of isoeugenol, 0.2 and 0.05%. Seven controls without isoeugenol allergy were also included. The participants applied 3.72 +/- 1.57 (mean +/- SD) mg/cm(2) of coded isoeugenol solutions twice a day to a 3 x 3 cm(2) area on the volar aspect...... of the right and left arm, respectively. For each test site the applications continued until a reaction appeared or for a maximum of 28 days. The minimal criteria for a positive reaction regarded as allergic contact dermatitis was persistent erythema at the ROAT test site. All controls were negative and 16...

  15. Eliciting ethical and social values in health technology assessment: A participatory approach.

    Science.gov (United States)

    Bombard, Yvonne; Abelson, Julia; Simeonov, Dorina; Gauvin, Francois-Pierre

    2011-07-01

    Despite a growing consensus that ethical and social values should be addressed in health technology assessment (HTA) processes, there exist a variety of methods for doing so. There is growing interest in involving citizens in policy development to ensure that decisions are legitimate, and reflect the broad social values of the public. We sought to bring these issues together by employing a participatory approach to elicit ethical and social values in HTA. Our primary objective was to elicit a set of ethical and social values from citizens that could be used to guide Ontario's HTA evidentiary review and appraisal process. A secondary objective was to explore the feasibility of using participatory approaches to elicit these values. A 14-person Citizens' Reference Panel on Health Technologies was established to provide input to the Ontario Health Technology Advisory Committee in developing its recommendations. A mixed methods approach was used where informed, deliberative discussions were combined with pre- and post-questionnaires, which assessed the relative importance of various ethical and social values as well as their stability over time. Over the course of five meetings, panel members progressed toward the identification of a set of core values -universal access, choice and quality care. These values were consistently prioritized as the core values that should be considered in the evaluation of health technologies and ensuing recommendations. Sustained and deliberative methods, like a citizens' panel, offer a promising approach for eliciting ethical and social values into HTA. Copyright © 2011 Elsevier Ltd. All rights reserved.

  16. Collage Life Story Elicitation Technique: A Representational Technique for Scaffolding Autobiographical Memories

    Science.gov (United States)

    van Schalkwyk, Gertina J.

    2010-01-01

    A basic premise in narrative therapy and inquiry is that life story telling is a mechanism by which experiences are rendered meaningful within some form of structure. However, narrative inquiry has to take cognisance of difficulties ensuing from discursive practices for different populations when eliciting their life stories. In this article I…

  17. Lexical Difficulty--Using Elicited Imitation to Study Child L2

    Science.gov (United States)

    Campfield, Dorota E.

    2017-01-01

    This paper reports a post-hoc analysis of the influence of lexical difficulty of cue sentences on performance in an elicited imitation (EI) task to assess oral production skills for 645 child L2 English learners in instructional settings. This formed part of a large-scale investigation into effectiveness of foreign language teaching in Polish…

  18. Testing Moral Foundation Theory: Are Specific Moral Emotions Elicited by Specific Moral Transgressions?

    Science.gov (United States)

    Landmann, Helen; Hess, Ursula

    2018-01-01

    Moral foundation theory posits that specific moral transgressions elicit specific moral emotions. To test this claim, participants (N = 195) were asked to rate their emotions in response to moral violation vignettes. We found that compassion and disgust were associated with care and purity respectively as predicted by moral foundation theory.…

  19. Understanding hospital meal experiences by means of Participant-Driven-Photo-Elicitation

    DEFF Research Database (Denmark)

    Justesen, Lise; Mikkelsen, Bent Egberg; Gyimóthy, Szilvia

    2014-01-01

    A patients’ hospital meal experiences can be complex and often difficult to capture using traditional methods. This study investigated patients’ hospital meal experiences using participant-driven-photo-elicitation (PDPE). PDPE invites respondents to photograph their daily lives and combines this ...

  20. RiskREP: Risk-Based Security Requirements Elicitation and Prioritization (extended version)

    NARCIS (Netherlands)

    Herrmann, Andrea; Morali, A.

    2010-01-01

    Today, companies are required to be in control of the security of their IT assets. This is especially challenging in the presence of limited budgets and conflicting requirements. Here, we present Risk-Based Requirements Elicitation and Prioritization (RiskREP), a method for managing IT security

  1. A framework for characterizing usability requirements elicitation and analysis methodologies (UREAM)

    NARCIS (Netherlands)

    Trienekens, J.J.M.; Kusters, R.J.; Mannaert, H.

    2012-01-01

    Dedicated methodologies for the elicitation and analysis of usability requirements have been proposed in literature, usually developed by usability experts. The usability of these approaches by non-expert software engineers is not obvious. In this paper, the objective is to support developers and

  2. Scenario-based Requirements Elicitation in a Pain-teletreatment Application

    NARCIS (Netherlands)

    Widya, I.A.; Bults, Richard G.A.; Huis in 't Veld, M.H.A.; Vollenbroek-Hutten, Miriam Marie Rosé; Shishkov, Boris; Cordeiro, J.; Ranchordas, A.

    2009-01-01

    This paper proposes a way to elicit requirements in the domain of eHealth, in particular telemedicine treatment, that is in alignment with the evidence based working practice in medicine. In collaboration with ICT developers, medical professionals co-shape the intended system, which has to support

  3. Improving the Communication Skills of IS Developers during Requirements Elicitation Using Experiential Learning

    Science.gov (United States)

    Qurban, Mustafa H.; Austria, Richmond D.

    2009-01-01

    The improvement of communication skills among Information Systems (IS) developers can be considered as a strategy to mitigate the risk of project failure during IS design. This paper addresses issues on various communication barriers normally encountered during its requirements elicitation (RE) stage. This study aims to adopt experiential learning…

  4. A Framework for Requirement Elicitation, Analysis, Documentation and Prioritisation under Uncertainty

    NARCIS (Netherlands)

    Rajabali Nejad, Mohammadreza; Mladenov, V.

    2015-01-01

    This paper offers a pluralistic framework for coping with requirements in the early phases of design where there is lack of knowledge about a system, its architect and functions. The framework is used to elicit, analyze, document and prioritize the requirements. It embeds probabilistic approach and

  5. Elicited Bid Functions in a (a)Symmetric First-Price Auctions

    NARCIS (Netherlands)

    Pezanis-Christou, P.; Sadrieh, A.

    2003-01-01

    We report on a series of experiments that examine bidding behavior in first-price sealed bid auctions with symmetric and asymmetric bidders.To study the extent of strategic behavior, we use an experimental design that elicits bidders complete bid functions in each round (auction) of the

  6. Students' Affordance of Teleologic Explanations and Anthropomorphic Language in Eliciting Concepts in Physics

    Science.gov (United States)

    Bautista, Romiro G.

    2015-01-01

    This study ascertains that the students' affordance of teleologic explanations and anthropomorphic language in eliciting concepts in Physics is influenced by their age and learning exposure and experience. Using Explicative-Reductive Method of Descriptive Research, this study focused on the determinants of students' affordance of…

  7. Children with Autism Respond Differently to Spontaneous, Elicited and Deferred Imitation

    Science.gov (United States)

    Heimann, M.; Nordqvist, E.; Strid, K.; Connant Almrot, J.; Tjus, T.

    2016-01-01

    Background: Imitation, a key vehicle for both cognitive and social development, is often regarded as more difficult for children with autism spectrum disorders (ASD) than for children with Down syndrome (DS) or typically developing (TD) children. The current study investigates similarities and differences in observed elicited, spontaneous and…

  8. Understanding the effect of adaptive preference elicitation methods on user satisfaction of a recommender system

    NARCIS (Netherlands)

    Knijnenburg, B.P.; Willemsen, M.C.

    2009-01-01

    In a recommender system that suggests options based on user attribute weights, the method of preference elicitation (PE) employed by a recommender system can influence users' satisfaction with the system, as well as the perceived usefulness and the understandability of the system. Specifically, we

  9. The effect of preference elicitation methods on the user experience of a recommender system

    NARCIS (Netherlands)

    Knijnenburg, B.P.; Willemsen, M.C.

    2010-01-01

    To increase the user experience, preference elicitation methods used by recommender systems can be adapted to individual differences such as the level of expertise. However, we will show that the satisfaction and perceived usefulness of a recommender system also depends strongly on subtle variations

  10. Using a knowledge elicitation method to specify the business model of a human factors organization

    NARCIS (Netherlands)

    Schraagen, J.M.C.; Ven, J. van de; Hoffman, R.R.; Moon, B.M.

    2009-01-01

    Concept Mapping was used to structure knowledge elicitation interviews with a group of human factors specialists whose goal was to describe the business model of their Department. This novel use of cognitive task analysis to describe the business model of a human factors organization resulted in a

  11. Using a knowledge elicitation method to specify the business model of a human factors organization.

    NARCIS (Netherlands)

    Schraagen, Johannes Martinus Cornelis; van de Ven, Josine; Hoffman, Robert R.; Moon, Brian M.

    2009-01-01

    Concept Mapping was used to structure knowledge elicitation interviews with a group of human factors specialists whose goal was to describe the business model of their Department. This novel use of cognitive task analysis to describe the business model of a human factors organization resulted in a

  12. Business Process Elicitation, Modeling, and Reengineering: Teaching and Learning with Simulated Environments

    Science.gov (United States)

    Jeyaraj, Anand

    2010-01-01

    The design of enterprise information systems requires students to master technical skills for elicitation, modeling, and reengineering business processes as well as soft skills for information gathering and communication. These tacit skills and behaviors cannot be effectively taught students but rather experienced and learned by students. This…

  13. Differential Neural Activity during Search of Specific and General Autobiographical Memories Elicited by Musical Cues

    Science.gov (United States)

    Ford, Jaclyn Hennessey; Addis, Donna Rose; Giovanello, Kelly S.

    2011-01-01

    Previous neuroimaging studies that have examined autobiographical memory specificity have utilized retrieval cues associated with prior searches of the event, potentially changing the retrieval processes being investigated. In the current study, musical cues were used to naturally elicit memories from multiple levels of specificity (i.e., lifetime…

  14. Cr(III) and Cr(VI) in leather and elicitation of eczema

    DEFF Research Database (Denmark)

    Hansen, Malene Barré; Menne, Torkil; Johansen, Jeanne Duus

    2006-01-01

    The aim of the present study was to investigate the relation between the content of Cr(VI) and soluble Cr(III) in leather and the ability of the leather to elicit eczema in chromium allergic patients. An array of chromium-tanned leather samples was analysed for the content of total Cr(VI) and sol...

  15. Eliciting and Developing Teachers' Conceptions of Random Processes in a Probability and Statistics Course

    Science.gov (United States)

    Smith, Toni M.; Hjalmarson, Margret A.

    2013-01-01

    The purpose of this study is to examine prospective mathematics specialists' engagement in an instructional sequence designed to elicit and develop their understandings of random processes. The study was conducted with two different sections of a probability and statistics course for K-8 teachers. Thirty-two teachers participated. Video analyses…

  16. Identification and Characterization of Ixodes scapularis Antigens That Elicit Tick Immunity Using Yeast Surface Display

    NARCIS (Netherlands)

    Schuijt, T.J.; Narasimhan, S.; Daffre, S.; Deponte, K.; Hovius, J.W.R.; van 't Veer, C.; van der Poll, T.; Bakhtiari, K.; Meijers, J.C.M.; Boder, E.T.; van Dam, A.P.; Fikrig, E.

    2011-01-01

    Repeated exposure of rabbits and other animals to ticks results in acquired resistance or immunity to subsequent tick bites and is partially elicited by antibodies directed against tick antigens. In this study we demonstrate the utility of a yeast surface display approach to identify tick salivary

  17. Variation in accumulation of isoflavonoids in Phaseoleae seedlings elicited by Rhizopus

    NARCIS (Netherlands)

    Aisyah, Siti; Gruppen, Harry; Andini, Silvia; Bettonvil, Monique; Severing, Eduard; Vincken, Jean Paul

    2016-01-01

    Seeds from seven species of tribe Phaseoleae, i.e. Phaseolus, Vigna, Lablab and Psophocarpus, were investigated for inducibility of isoflavonoids by germination with or without subsequent elicitation with Rhizopus oryzae. Germination alone poorly induced isoflavonoid production (in the range of

  18. The Acquisition of Auxiliary Syntax: A Longitudinal Elicitation Study. Part 2: The Modals and Auxiliary DO

    Science.gov (United States)

    Rowland, Caroline F.; Theakston, Anna L.

    2009-01-01

    Purpose: The study of auxiliary acquisition is central to work on language development and has attracted theoretical work from both nativist and constructivist approaches. This study is part of a 2-part companion set that represents a unique attempt to trace the development of auxiliary syntax by using a longitudinal elicitation methodology. The…

  19. Motivating and achievement-eliciting pop-ups in online environments: A user experience perspective

    NARCIS (Netherlands)

    Bittner, Jenny; Zondervan, Robin

    2015-01-01

    The aim of the present research was to develop pop-up windows that motivate users and evoke a positive user experience. Several variants of achievement eliciting pop-ups were designed and tested on a real business-website. A pre-test examined the effectiveness of 24 combinations of pictures and

  20. Early Morphological Productivity in Hungarian: Evidence from Sentence Repetition and Elicited Production

    Science.gov (United States)

    Gabor, Balint; Lukacs, Agnes

    2012-01-01

    This paper investigates early productivity of morpheme use in Hungarian children aged between 2 ; 1 and 5 ; 3. Hungarian has a rich morphology which is the core marker of grammatical functions. A new method is introduced using the novel word paradigm in a sentence repetition task with masked inflections (i.e. a disguised elicited production task).…

  1. Differences between Spontaneous and Elicited Expressive Communication in Children with Autism

    Science.gov (United States)

    Chiang, Hsu-Min

    2009-01-01

    The purpose of this study was to investigate the differences between spontaneous and elicited expressive communication in Australian and Taiwanese children with autism who were nonverbal or had limited speech. Thirty-four children with autism (17 Australian and 17 Taiwanese children) participated in this study. Each participant was observed for 2…

  2. Promoting Parent and Child Physical Activity Together: Elicitation of Potential Intervention Targets and Preferences

    Science.gov (United States)

    Rhodes, Ryan E.; Lim, Clarise

    2018-01-01

    Promoting physical activities that involve both parents and their children would be very useful to the improved health and well-being of families, yet coactivity interventions have been particularly unsuccessful in past research. The purpose of this study was to elicit the salient parental beliefs about coactivity framed through theory of planned…

  3. Explaining Distortions in Utility Elicitation through the Rank-Dependent Model for Risky Choices

    NARCIS (Netherlands)

    P.P. Wakker (Peter); A.M. Stiggelbout (Anne)

    1995-01-01

    textabstractThe standard gamble (SG) method has been accepted as the gold standard for the elicitation of utility when risk or uncertainty is involved in decisions, and thus for the measurement of utility in medical decisions. Unfortunately, the SG method is distorted by a general dislike for

  4. Grounded in the landscape: Eliciting farmers' understanding of soil and soil fertility, Mali (West Africa)

    OpenAIRE

    Crane, T.

    2002-01-01

    In order to develop convincing messages and sustainable interventions, it is necessary to understand how farmers themselves perceive soil conditions and how these perceptions influence their soil management and land use decisions. This brief illustrates an ethno-scientific methodology for eliciting farmers' conceptualization of soil and soil fertility.

  5. Infection-derived lipids elicit a novel immune deficiency circuitry in arthropods

    Science.gov (United States)

    The insect Immune Deficiency (IMD) pathway resembles the tumor necrosis factor receptor network in mammals and senses diaminopimelic-type peptidoglycans present in Gram-negative bacteria. Whether unidentified chemical moieties elicit the IMD signaling cascade remains unknown. Here, we disclose thoug...

  6. Pursenality : A photo-ethnographic method for self-elicitation and co-creation

    NARCIS (Netherlands)

    Mulder, J.W.; Mulder, I.J.; Best, S.E.

    2013-01-01

    The current work introduces pursenality, a photoethnographic method for self-elicitation and cocreation, which elaborates upon current photography methods used in (design) ethnography. In total 91 bachelor students in the 6th semester participated in a purse diary study and used the pursenality

  7. Feedback on Feedback: Eliciting Learners' Responses to Written Feedback through Student-Generated Screencasts

    Science.gov (United States)

    Fernández-Toro, María; Furnborough, Concha

    2014-01-01

    Despite the potential benefits of assignment feedback, learners often fail to use it effectively. This study examines the ways in which adult distance learners engage with written feedback on one of their assignments. Participants were 10 undergraduates studying Spanish at the Open University, UK. Their responses to feedback were elicited by means…

  8. Phagostimulants for the Asian citrus psyllid also elicit volatile release from citrus leaves

    Science.gov (United States)

    Chemical cues that elicit orientation by the Asian citrus psyllid, Diaphorina citri Kuwayama (Hemiptera: Liviidae), are of great interest because it is the primary vector of the causal pathogen of citrus greening disease. We identified an optimal blend ratio of formic and acetic acids that stimulate...

  9. Allergens in combination have a synergistic effect on the elicitation response

    DEFF Research Database (Denmark)

    Johansen, J D; Skov, L; Volund, A

    1998-01-01

    Perfume ingredients were chosen as model substances to study the effect of allergens in combination on the elicitation response. Two groups of eczema patients were studied. One consisted of 18 subjects with a contact allergy to two fragrance substances and the other was a control group of 15 subj...

  10. Elicitation Techniques: Getting People to Talk about Ideas They Don't Usually Talk About

    Science.gov (United States)

    Barton, Keith C.

    2015-01-01

    Elicitation techniques are a category of research tasks that use visual, verbal, or written stimuli to encourage participants to talk about their ideas. These tasks are particularly useful for exploring topics that may be difficult to discuss in formal interviews, such as those that involve sensitive issues or rely on tacit knowledge. Elicitation…

  11. N-acetylcysteine manipulation fails to elicit an increase in glutathione in a teleost model

    DEFF Research Database (Denmark)

    Birnie-Gauvin, Kim; Larsen, Martin Hage; Aarestrup, Kim

    2018-01-01

    and vegetable shortening, at two different concentrations (100 and 400 mg/kg), with the appropriate controls and shams, under controlled laboratory settings. We found that NAC failed to elicit an increase in GSH over three time periods and concluded that NAC is not an effective method to enhance GSH levels...

  12. Safety Risk Knowledge Elicitation in Support of Aeronautical R and D Portfolio Management: A Case Study

    Science.gov (United States)

    Shih, Ann T.; Ancel, Ersin; Jones, Sharon Monica; Reveley, Mary S.; Luxhoj, James T.

    2012-01-01

    Aviation is a problem domain characterized by a high level of system complexity and uncertainty. Safety risk analysis in such a domain is especially challenging given the multitude of operations and diverse stakeholders. The Federal Aviation Administration (FAA) projects that by 2025 air traffic will increase by more than 50 percent with 1.1 billion passengers a year and more than 85,000 flights every 24 hours contributing to further delays and congestion in the sky (Circelli, 2011). This increased system complexity necessitates the application of structured safety risk analysis methods to understand and eliminate where possible, reduce, and/or mitigate risk factors. The use of expert judgments for probabilistic safety analysis in such a complex domain is necessary especially when evaluating the projected impact of future technologies, capabilities, and procedures for which current operational data may be scarce. Management of an R&D product portfolio in such a dynamic domain needs a systematic process to elicit these expert judgments, process modeling results, perform sensitivity analyses, and efficiently communicate the modeling results to decision makers. In this paper a case study focusing on the application of an R&D portfolio of aeronautical products intended to mitigate aircraft Loss of Control (LOC) accidents is presented. In particular, the knowledge elicitation process with three subject matter experts who contributed to the safety risk model is emphasized. The application and refinement of a verbal-numerical scale for conditional probability elicitation in a Bayesian Belief Network (BBN) is discussed. The preliminary findings from this initial step of a three-part elicitation are important to project management practitioners as they illustrate the vital contribution of systematic knowledge elicitation in complex domains.

  13. Severity of dependence modulates smokers' neuronal cue reactivity and cigarette craving elicited by tobacco advertisement.

    Science.gov (United States)

    Vollstädt-Klein, Sabine; Kobiella, Andrea; Bühler, Mira; Graf, Caroline; Fehr, Christoph; Mann, Karl; Smolka, Michael N

    2011-01-01

    Smoking-related cues elicit craving and mesocorticolimbic brain activation in smokers. Severity of nicotine dependence seems to moderate cue reactivity, but the direction and mechanisms of its influence remains unclear. Although tobacco control policies demand a ban on tobacco advertising, cue reactivity studies in smokers so far have not employed tobacco advertisement as experimental stimuli. We investigated whether tobacco advertisement elicits cue reactivity at a behavioral (subjective craving) and a neural level (using functional magnetic resonance imaging) in 22 smokers and 21 never-smokers. Moreover, we studied the influence of severity of dependence on cue reactivity. In smokers, tobacco advertisement elicited substantially more craving than control advertisement whereas never-smokers reported no cue induced craving. Surprisingly, neuronal cue reactivity did not differ between smokers and never-smokers. Moderately dependent smokers' craving increased over the course of the experiment, whereas highly dependent smokers' craving was unaffected. Moderately dependent smokers' brain activity elicited by tobacco advertisement was higher in the amygdala, hippocampus, putamen and thalamus compared with highly dependent smokers. Furthermore, limbic brain activation predicted picture recognition rates after the scanning session, even in never-smokers. Our findings show that tobacco advertisement elicits cigarette craving and neuronal cue reactivity primarily in moderately dependent smokers, indicating that they might be particularly responsive towards external smoking-related cues. On the other hand, neuronal cue reactivity and cigarette craving in highly dependent smokers is more likely triggered by internal cues such as withdrawal symptoms. Tobacco advertisement seems to likewise appeal to smokers and non-smokers, clarifying the potential danger especially for young non-smokers. © 2010 The Authors, Addiction Biology © 2010 Society for the Study of Addiction.

  14. Unsaturated fatty acids show clear elicitation responses in a modified local lymph node assay with an elicitation phase, and test positive in the direct peptide reactivity assay.

    Science.gov (United States)

    Yamashita, Kunihiko; Shinoda, Shinsuke; Hagiwara, Saori; Miyazaki, Hiroshi; Itagaki, Hiroshi

    2015-12-01

    The Organisation for Economic Co-operation and Development (OECD) Test Guidelines (TG) adopted the murine local lymph node assay (LLNA) and guinea pig maximization test (GPMT) as stand-alone skin sensitization test methods. However, unsaturated carbon-carbon double-bond and/or lipid acids afforded false-positive results more frequently in the LLNA compared to those in the GPMT and/or in human subjects. In the current study, oleic, linoleic, linolenic, undecylenic, fumaric, maleic, and succinic acid and squalene were tested in a modified LLNA with an elicitation phase (LLNA:DAE), and in a direct peptide reactivity assay (DPRA) to evaluate their skin-sensitizing potential. Oleic, linoleic, linolenic, undecylenic and maleic acid were positive in the LLNA:DAE, of which three, linoleic, linolenic, and maleic acid were positive in the DPRA. Furthermore, the results of the cross-sensitizing tests using four LLNA:DAE-positive chemicals were negative, indicating a chemical-specific elicitation response. In a previous report, the estimated concentration needed to produce a stimulation index of 3 (EC3) of linolenic acid, squalene, and maleic acid in the LLNA was LLNA. However, the skin-sensitizing potential of all LLNA:DAE-positive chemicals was estimated as weak. These results suggested that oleic, linoleic, linolenic, undecylenic, and maleic acid had skin-sensitizing potential, and that the LLNA overestimated the skin-sensitizing potential compared to that estimated by the LLNA:DAE.

  15. Development of a respiratory sensitization/elicitation protocol of toluene diisocyanate (TDI) in Brown Norway rats to derive an elicitation-based occupational exposure level

    International Nuclear Information System (INIS)

    Pauluhn, Jürgen

    2014-01-01

    Highlights: • Toluene diisocyanate (TDI) was unequivocally identified as asthmagens in BN-rats. • The elicitation response on BAL-PMN was threshold-dose dependent. • The elicitation of asthma-like responses follow a concentration × time-relationship. • The human-equivalent dose–response was duplicated in rats. • The derived occupational exposure level (OEL) matches current standards. - Abstract: Toluene diisocyanate (TDI), a known human asthmagen, was investigated in skin-sensitized Brown Norway rats for its concentration × time (C × t)-response relationship on elicitation-based endpoints. The major goal of study was to determine the elicitation inhalation threshold dose in sensitized, re-challenged Brown Norway rats, including the associated variables affecting the dosimetry of inhaled TDI-vapor in rats and as to how these differences can be translated to humans. Attempts were made to duplicate at least some traits of human asthma by using skin-sensitized rats which were subjected to single or multiple inhalation-escalation challenge exposures. Two types of dose-escalation protocols were used to determine the elicitation-threshold C × t; one used a variable C (C var ) and constant t (t const ), the other a constant C (C const ) and variable t (t var ). The selection of the ''minimal irritant'' C was based an ancillary pre-studies. Neutrophilic granulocytes (PMNs) in bronchoalveolar lavage fluid (BAL) were considered as the endpoint of choice to integrate the allergic pulmonary inflammation. These were supplemented by physiological measurements characterizing nocturnal asthma-like responses and increased nitric oxide in exhaled breath (eNO). The C const × t var regimen yielded the most conclusive dose–response relationship as long C was high enough to overcome the scrubbing capacity of the upper airways. Based on ancillary pre-studies in naïve rats, the related human-equivalent respiratory tract irritant threshold

  16. A Measure of Proficiency or Short-Term Memory? Validation of an Elicited Imitation Test for SLA Research

    Science.gov (United States)

    Kim, Youjin; Tracy-Ventura, Nicole; Jung, Yeonjoo

    2016-01-01

    Elicited imitation requires listeners to listen and repeat sentences as accurately as possible. In second language acquisition (SLA) research it has been used for a variety of purposes. Recently, versions of the same elicited imitation test (EIT) have been created in 6 languages with the purpose of measuring second language proficiency (Ortega…

  17. Pre-Service Teachers' Modelling Processes through Engagement with Model Eliciting Activities with a Technological Tool

    Science.gov (United States)

    Daher, Wajeeh M.; Shahbari, Juhaina Awawdeh

    2015-01-01

    Engaging mathematics students with modelling activities helps them learn mathematics meaningfully. This engagement, in the case of model eliciting activities, helps the students elicit mathematical models by interpreting real-world situation in mathematical ways. This is especially true when the students utilize technology to build the models.…

  18. DMPD: Macrophage activation through CCR5- and CXCR4-mediated gp120-elicited signalingpathways. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 12960231 Macrophage activation through CCR5- and CXCR4-mediated gp120-elicited sign...82. Epub 2003 Jul 22. (.png) (.svg) (.html) (.csml) Show Macrophage activation through CCR5- and CXCR4-media...on through CCR5- and CXCR4-mediated gp120-elicited signalingpathways. Authors Lee C, Liu QH, Tomkowicz B, Yi

  19. Effects of penicillin on procaine-elicited bursts of potential in central neuron of snail, Achatina fulica.

    Science.gov (United States)

    Chen, Yi-Hung; Lu, Kuan-Ling; Hsiao, Ru-Wan; Lee, Ya-Ling; Tsai, Hong-Chieh; Lin, Chia Hsien; Tsai, Ming-Cheng

    2008-08-01

    Effects of penicillin on changes in procaine-elicited bursts of potential (BoP) were studied in a central neuron (RP4) of snail, Achatina fulica Ferussac. Procaine elicited BoP in the RP4 neuron while penicillin elicited depolarization of the neuron. Penicillin decreased the BoP elicited by procaine in a concentration-dependent manner. The effect of penicillin on the procaine-elicited BoP was not altered in the preparations treated with ascorbate or L-NAME (N-nitro-L-arginine methyl ester). However, the inhibitory effect of penicillin on the procaine-elicited BoP was enhanced with a decrease in extracellular sodium ion. Sodium ion was one of the important ions contributing to the action potential of the neuron. Two-electrode voltage-clamp studies revealed that penicillin decreased the fast sodium inward current of the neuron. It is concluded that penicillin inhibited the BoP elicited by procaine and sodium ion altered the effect of penicillin on procaine-elicited BoP.

  20. N400 elicited by incongruent ending words of Chinese idioms in healthy adults.

    Science.gov (United States)

    Chen, Xing-shi; Tang, Yun-xiang; Xiao, Ze-ping; Wang, Ji-jun; Zhang, Ming-dao; Zhang, Zai-fu; Hu, Zhen-yu; Lou, Fei-ying; Chen, Chong; Zhang, Tian-hong

    2010-03-20

    Prior research about N400 has been mainly based on English stimuli, while the cognitive processing of Chinese characters is still unclear. The aim of the present study was to further investigate the semantic processing of Chinese idioms. Event related potentials (ERP) component N400 was elicited by 38 pairs of matching (congruent) and mismatching (incongruent) ended Chinese idioms: ending words with same phoneme but different shape and meaning (sPdSdM), with similar shape but different phoneme and meaning (sSdPdM), with same meaning but different phoneme and shape (sMdPdS), and words with different phoneme, shape and meaning (dPdSdM) and recorded by Guangzhou Runjie WJ-1 ERP instruments. In 62 right-handed healthy adults (age 19 - 50 years), N400 amplitudes and latencies were compared between matching and mismatching conditions at Fz, Cz and Pz. N400 showed a midline distribution and could be elicited in electrodes Fz, Cz and Pz. The mean values of N400 latencies and amplitudes were obtained for matching and mismatching ending words in healthy adults. Significant differences were found in N400 latencies and amplitudes in matching and mismatching ending-words idioms in healthy adults (P idioms, N400 latencies were prolonged and the amplitudes were increased in mismatching ones. N400s elicited by different types of stimuli showed different latencies and amplitudes, and longest N400 latency and largest N400 amplitude were elicited by ending-words with dPdSdM. No gender difference was found of N400 latency and amplitude in this study (P > 0.05). Compared with English stimuli, Chinese ideographic words could provide more flexible stimuli for N400 research in that the words have 3-dimension changes - phoneme, shape and meaning. Features of N400 elicited by matching and mismatching ending words in Chinese idioms are mainly determined by the meaning of the word. Some issues of N400 elicited by Chinese characters deserve further research.

  1. Antistaphylococcal activity of dalbavancin, an experimental glycopeptide.

    Science.gov (United States)

    Lin, Gengrong; Credito, Kim; Ednie, Lois M; Appelbaum, Peter C

    2005-02-01

    Dalbavancin, tested against 146 staphylococci, was more potent than other drugs tested, with an MIC at which 50% of staphylococci were inhibited of 0.03 microg/ml and an MIC at which 90% of staphylococci were inhibited of 0.06 microg/ml by microdilution. For all strains, MICs of vancomycin, linezolid, ranbezolid, oritavancin, daptomycin, and quinupristin-dalfopristin were

  2. Photo elicitation interviews as a way of accessing primary school students' attitudes

    DEFF Research Database (Denmark)

    Nissen, Stine Karen; Schmidt, Maria Christina Secher; Tonnesen, Pia Beck

    explores the potential of photo-elicitation interviews as a qualitative path to affect. This particular type of interview is shaped as conversations about self-produced images of mathematics. When conducting the photo elicitation interviews, researchers also introduce their own photographs......The identification of the right prompts, to which young children can respond easily, is a challenge to researchers, even more so when it comes to studies of affect (McDonough and Sullivan, 2014). Attempting to capture 3rd grade students’ verbalized perspectives on mathematics, this study also...... into the interview context, along with the photographs of the child's experiences. Both serve as the basis for a child-directed interview (Clark, 1999)....

  3. The capsaicin cough reflex in patients with symptoms elicited by odorous chemicals

    DEFF Research Database (Denmark)

    Holst, H; Arendt-Nielsen, L; Mosbech, H

    2010-01-01

    Patients with multiple chemical sensitivity and eczema patients with airway symptoms elicited by odorous chemicals have enhanced cough reflex to capsaicin when applying the tidal breathing method. The aims of the present study were to test whether the capsaicin induced cough reflex was enhanced...... when applying the single breath inhalation method in similar groups of patients with symptoms related to odorous chemicals e.g. other persons wearing of perfume; and to investigate to what extent the reporting of lower airway symptoms influenced the cough reflex. Sixteen patients fulfilling Cullen......'s criteria for multiple chemical sensitivity and 15 eczema patients with airway symptoms elicited by odorous chemicals were compared with 29 age-matched, healthy controls. We measured C5--the capsaicin concentration causing five coughs or more--using the single breath inhalation test. No difference was found...

  4. A Comparison of Active and Passive Virtual Reality Exposure Scenarios to Elicit Social Anxiety

    Directory of Open Access Journals (Sweden)

    Yoones A. Sekhavat

    2017-06-01

    Full Text Available Social phobia is an anxiety disorder that results in an excessive and unreasonable fear of social situations. As a safe and controlled tool, Virtual Reality Exposure Therapy (VRET has been used to treat anxiety disorders and phobias. This paper aims to study whether VRET with active scenarios can challenge a person more than passive scenarios. By comparing participants who were exposed to active and passive scenarios in VRET, we show that active scenarios are more effective than passive scenarios to elicit social anxiety in healthy participants. We focus on eliciting social anxiety and creating the sense of presence as two parameters enhancing the efficacy of VRET scenarios.

  5. Brain activity elicited by positive and negative feedback in preschool-aged children.

    Directory of Open Access Journals (Sweden)

    Xiaoqin Mai

    2011-04-01

    Full Text Available To investigate the processing of positive vs. negative feedback in children aged 4-5 years, we devised a prize-guessing game that is analogous to gambling tasks used to measure feedback-related brain responses in adult studies. Unlike adult studies, the feedback-related negativity (FRN elicited by positive feedback was as large as that elicited by negative feedback, suggesting that the neural system underlying the FRN may not process feedback valence in early childhood. In addition, positive feedback, compared with negative feedback, evoked a larger P1 over the occipital scalp area and a larger positive slow wave (PSW over the right central-parietal scalp area. We believe that the PSW is related to emotional arousal and the intensive focus on positive feedback that is present in the preschool and early school years has adaptive significance for both cognitive and emotional development during this period.

  6. Eliciting change in at-risk elders (ECARE): evaluation of an elder abuse intervention program.

    Science.gov (United States)

    Mariam, Lydia Morris; McClure, Regina; Robinson, J B; Yang, Janet A

    2015-01-01

    The current study evaluated the effectiveness of a community-based elder abuse intervention program that assists suspected victims of elder abuse and self-neglect through a partnership with local law enforcement. This program, Eliciting Change in At-Risk Elders, involves building alliances with the elder and family members, connecting the elder to supportive services that reduce risk of further abuse, and utilizing motivational interviewing-type skills to help elders overcome ambivalence regarding making difficult life changes. Risk factors of elder abuse decreased over the course of the intervention and nearly three-quarters of participants made progress on their treatment goal, advancing at least one of Prochaska and DiClemente's (1983) stages of change (precontemplation, contemplation, preparation, action, and maintenance). Forty-three percent of elders moved into the stages of action and maintenance regarding their goal. The usefulness of eliciting change via longer-term relationships with vulnerable elders in entrenched elder abuse situations is discussed.

  7. Elicitation and use of expert judgment in performance assessment for high-level radioactive waste repositories

    International Nuclear Information System (INIS)

    Bonano, E.J.; Hora, S.C.; Keeney, R.L.; von Winterfeldt, D.

    1990-05-01

    This report presents the concept of formalizing the elicitation and use of expert judgment in the performance assessment of high-level radioactive waste (HLW) repositories in deep geologic formations. The report begins with a discussion of characteristics (advantages and disadvantages) of formalizing expert judgment examples of previous uses of expert judgment in radioactive waste programs, criteria that can assist in deciding when to formalize expert judgment, and the relationship of formal use of expert judgment to data collection and modeling. The current state of the art with respect to the elicitation, use, and communication of formal expert judgment is presented. The report concludes with a discussion on potential applications of formal expert judgment in performance assessment of HLW repositories. 93 refs

  8. No association between oxytocin receptor (OXTR gene polymorphisms and experimentally elicited social preferences.

    Directory of Open Access Journals (Sweden)

    Coren L Apicella

    Full Text Available BACKGROUND: Oxytocin (OXT has been implicated in a suite of complex social behaviors including observed choices in economic laboratory experiments. However, actual studies of associations between oxytocin receptor (OXTR gene variants and experimentally elicited social preferences are rare. METHODOLOGY/PRINCIPAL FINDINGS: We test hypotheses of associations between social preferences, as measured by behavior in two economic games, and 9 single nucleotide polymorphisms (SNPs of the OXTR gene in a sample of Swedish twins (n = 684. Two standard economic games, the dictator game and the trust game, both involving real monetary consequences, were used to elicit such preferences. After correction for multiple hypothesis testing, we found no significant associations between any of the 9 single nucleotide polymorphisms (SNPs and behavior in either of the games. CONCLUSION: We were unable to replicate the most significant association reported in previous research between the amount donated in a dictator game and an OXTR genetic variant.

  9. Functional Imaging of Human Vestibular Cortex Activity Elicited by Skull Tap and Auditory Tone Burst

    Science.gov (United States)

    Noohi, F.; Kinnaird, C.; Wood, S.; Bloomberg, J.; Mulavara, A.; Seidler, R.

    2016-01-01

    The current study characterizes brain activation in response to two modes of vestibular stimulation: skull tap and auditory tone burst. The auditory tone burst has been used in previous studies to elicit either the vestibulo-spinal reflex (saccular-mediated colic Vestibular Evoked Myogenic Potentials (cVEMP)), or the ocular muscle response (utricle-mediated ocular VEMP (oVEMP)). Some researchers have reported that air-conducted skull tap elicits both saccular and utricle-mediated VEMPs, while being faster and less irritating for the subjects. However, it is not clear whether the skull tap and auditory tone burst elicit the same pattern of cortical activity. Both forms of stimulation target the otolith response, which provides a measurement of vestibular function independent from semicircular canals. This is of high importance for studying otolith-specific deficits, including gait and balance problems that astronauts experience upon returning to earth. Previous imaging studies have documented activity in the anterior and posterior insula, superior temporal gyrus, inferior parietal lobule, inferior frontal gyrus, and the anterior cingulate cortex in response to different modes of vestibular stimulation. Here we hypothesized that skull taps elicit similar patterns of cortical activity as the auditory tone bursts, and previous vestibular imaging studies. Subjects wore bilateral MR compatible skull tappers and headphones inside the 3T GE scanner, while lying in the supine position, with eyes closed. Subjects received both forms of the stimulation in a counterbalanced fashion. Pneumatically powered skull tappers were placed bilaterally on the cheekbones. The vibration of the cheekbone was transmitted to the vestibular system, resulting in the vestibular cortical response. Auditory tone bursts were also delivered for comparison. To validate our stimulation method, we measured the ocular VEMP outside of the scanner. This measurement showed that both skull tap and auditory

  10. Drug-elicited systemic allergic (contact) dermatitis - update and possible pathomechanisms

    DEFF Research Database (Denmark)

    Maibach, H.I.; Thyssen, Jacob Pontoppidan

    2008-01-01

    . A heterogeneous clinical picture, in combination with limited insight to its pathomechanisms, makes such systemic reactions an area in need of further study. This article summarizes knowledge about systemic dermatitis elicited by drugs, with a special emphasis on possible pathomechanisms. A list of putative...... be misleading because skin contact is not a prerequisite, we suggest that the term 'systemic allergic dermatitis' should be used in the future Udgivelsesdato: 2008...

  11. Registered report: Tumour micro-environment elicits innate resistance to RAF inhibitors through HGF secretion

    OpenAIRE

    sprotocols

    2015-01-01

    Authors: David Blum, Samuel LaBarge, The Reproducibility Project: Cancer Biology†* ### Abstract The [Reproducibility Project: Cancer Biology](https://osf.io/e81xl/wiki/home/) seeks to address growing concerns about reproducibility in scientific research by conducting replications of 50 papers in the field of cancer biology published between 2010 and 2012. This Registered Report describes the proposed replication plan of key experiments from “Tumour micro-environment elicits innate res...

  12. Cue-elicited anxiety and craving for food using virtual reality scenarios

    OpenAIRE

    Ferrer, Marta (Ferrer García); Gutiérrez Maldonado, José; Pla Sanjuanelo, Joana

    2013-01-01

    Cue exposure therapy has been reported to be an effective intervention for reducing binge eating behavior in patients with eating disorders and obesity. However, in vivo food exposure conducted in the therapist's office presents logistical problems and lacks ecological validity. This study proposes the use of virtual reality technology as an alternative to in vivo exposure, and assesses the ability of different virtual environments to elicit anxiety and craving for food in a non-clinical samp...

  13. Using task analysis to improve the requirements elicitation in health information system.

    Science.gov (United States)

    Teixeira, Leonor; Ferreira, Carlos; Santos, Beatriz Sousa

    2007-01-01

    This paper describes the application of task analysis within the design process of a Web-based information system for managing clinical information in hemophilia care, in order to improve the requirements elicitation and, consequently, to validate the domain model obtained in a previous phase of the design process (system analysis). The use of task analysis in this case proved to be a practical and efficient way to improve the requirements engineering process by involving users in the design process.

  14. Flammable gas double shell tank expert elicitation presentations (Part A and Part B)

    Energy Technology Data Exchange (ETDEWEB)

    Bratzel, D.R.

    1998-04-17

    This document is a compilation of presentation packages and white papers for the Flammable Gas Double Shell Tank Expert Elicitation Workshop {number_sign}2. For each presentation given by the different authors, a separate section was developed. The purpose for issuing these workshop presentation packages and white papers as a supporting document is to provide traceability and a Quality Assurance record for future reference to these packages.

  15. From servicescape to consumptionscape: a photo-elicitation study of Starbucks in the New China

    OpenAIRE

    Meera Venkatraman; Teresa Nelson

    2008-01-01

    A servicescape can be viewed as the frozen potential of a consumptionscape, which is unleashed when consumers “twist” the resources of its built environment for their own purposes. In this paper we explore how young, urban Chinese consumers transform the iconic global brand Starbucks into a consumptionscape through their enactment of personally meaningful experiences, roles, and identities in the setting. We employ the qualitative research methodology of photo-elicitation by having consumers ...

  16. Prior elicitation: Interactive spreadsheet graphics with sliders can be fun, and informative

    OpenAIRE

    Jones, G; Johnson, WO

    2014-01-01

    There are several approaches to setting priors in Bayesian data analysis. Some attempt to minimize the impact of the prior on the posterior, allowing the data to "speak for themselves," or to provide Bayesian inferences that have good frequentist properties. In contrast, this note focuses on priors where scientific knowledge is used, possibly partially informative. There are many articles on the use of such subjective information. We focus on using standard software for eliciting priors from ...

  17. Eliciting Naturalistic Cortical Responses with a Sensory Prosthesis via Optimized Microstimulation

    Science.gov (United States)

    2016-08-12

    Eliciting naturalistic cortical responses with a sensory prosthesis via optimized microstimulation John S Choi1, Austin J Brockmeier2, David B...applied to single electrodes in the ventral caudal thalamus evoke percepts that are both place and modality-specific, and yet ‘unnatural’ in feeling ...information on touch parameters, they do so with the same timing, as would be expected for a biomimetic sensory prosthesis . The discriminability of natural

  18. A Fuzzy Galois Lattices Approach to Requirements Elicitation for Cloud Services

    OpenAIRE

    Todoran Koitz Irina; Glinz Martin

    2015-01-01

    The cloud paradigm has become increasingly attractive throughout the recent years due to its both technical and economic foreseen impact. Therefore, researchers’ and practitioners’ attention has been drawn to enhancing the technological characteristics of cloud services, such as performance, scalability or security. However, the topic of identifying and understanding cloud consumers’ real needs has largely been ignored. Existing requirements elicitation methods are not appropriate for the clo...

  19. Exploration of Hand Grasp Patterns Elicitable Through Non-Invasive Proximal Nerve Stimulation

    OpenAIRE

    Shin, Henry; Watkins, Zach; Hu, Xiaogang

    2017-01-01

    Various neurological conditions, such as stroke or spinal cord injury, result in an impaired control of the hand. One method of restoring this impairment is through functional electrical stimulation (FES). However, traditional FES techniques often lead to quick fatigue and unnatural ballistic movements. In this study, we sought to explore the capabilities of a non-invasive proximal nerve stimulation technique in eliciting various hand grasp patterns. The ulnar and median nerves proximal to th...

  20. Differential Neural Activity during Search of Specific and General Autobiographical Memories elicited by Musical Cues

    OpenAIRE

    Ford, Jaclyn Hennessey; Addis, Donna Rose; Giovanello, Kelly S.

    2011-01-01

    Previous neuroimaging studies that have examined autobiographical memory specificity have utilized retrieval cues associated with prior searches of the event, potentially changing the retrieval processes being investigated. In the current study, musical cues were used to naturally elicit memories from multiple levels of specificity (i.e., lifetime period, general event, and event-specific). Sixteen young adults participated in a neuroimaging study in which they retrieved autobiographical memo...

  1. N400 elicited by incongruent ending words of Chinese idioms in healthy adults

    Institute of Scientific and Technical Information of China (English)

    CHEN Xing-shi; ZHANG Tian-hong; TANG Yun-xiang; XIAO Ze-ping; WANG Ji-jun; ZHANG Ming-dao; ZHANG Zai-fu; HU Zhen-yu; LOU Fei-ying; CHEN Chong

    2010-01-01

    Background Prior research about N400 has been mainly based on English stimuli,while the cognitive.processing of Chinese characters is still unclear.The aim of the present study was to further investigate the semantic processing of Chinese idioms.Methods Event related potentials (ERP) component N400 was elicited by 38 pairs of matching (congruent) and mismatching (incongruent) ended Chinese idioms:ending words with same phoneme but different shape and meaning (sPdSdM),with similar shape but different phoneme and meaning(sSdPdM),with same meaning but different phoneme and shape(sMdPdS),and words with different phoneme,shape and meaning(dPdSdM)and recorded by Guangzhou Runjie WJ-1 ERP instruments.In 62 right-handed healthy adults(age 19-50 years),N400 amplitudes and latencies were compared between matching and mismatching conditions at Fz,Cz and Pz.Results N400 showed a midline distribution and could be elicited in electrodes Fz, Cz and Pz.The mean values of N400 latencies and amplitudes were obtained for matching and mismatching ending werds in healthy adults.Significant differences were found in N400 latencies and amplitudes in matching and mismatching ending-werds idioms in healthy adults(P0.05).Conclusions Compared with English stimuli.Chinese ideographic words could provide more flexible stimuli for N400 research in that the werds have 3-dimension changes-phoneme.shape and meaning.Features of N400 elicited by matching and mismatching ending words in Chinese idioms are mainly determined by the meaning of the werd.Some issues of N400 elicited by Chinese characters deserve further research.

  2. Viewing pain and happy faces elicited similar changes in postural body sway.

    Directory of Open Access Journals (Sweden)

    Juan Gea

    Full Text Available Affective facial expressions are potent social cues that can induce relevant physiological changes, as well as behavioral dispositions in the observer. Previous studies have revealed that angry faces induced significant reductions in body sway as compared with neutral and happy faces, reflecting an avoidance behavioral tendency as freezing. The expression of pain is usually considered an unpleasant stimulus, but also a relevant cue for delivering effective care and social support. Nevertheless, there are few data about behavioral dispositions elicited by the observation of pain expressions in others. The aim of the present research was to evaluate approach-avoidance tendencies by using video recordings of postural body sway when participants were standing and observing facial expressions of pain, happy and neutral. We hypothesized that although pain faces would be rated as more unpleasant than the other faces, they would provoke significant changes in postural body sway as compared to neutral facial expressions. Forty healthy female volunteers (mean age 25 participated in the study. Amplitude of forward movements and backward movements in the anterior-posterior and medial-lateral axes were obtained. Statistical analyses revealed that pain faces were the most unpleasant stimuli, and that both happy and pain faces were more arousing than neutral ones. Happy and pain faces also elicited greater amplitude of body sway in the anterior-posterior axes as compared with neutral faces. In addition, significant positive correlations were found between body sway elicited by pain faces and pleasantness and empathic ratings, suggesting that changes in postural body sway elicited by pain faces might be associated with approach and cooperative behavioral responses.

  3. Flammable gas double shell tank expert elicitation presentations (Part A and Part B)

    International Nuclear Information System (INIS)

    Bratzel, D.R.

    1998-01-01

    This document is a compilation of presentation packages and white papers for the Flammable Gas Double Shell Tank Expert Elicitation Workshop number-sign 2. For each presentation given by the different authors, a separate section was developed. The purpose for issuing these workshop presentation packages and white papers as a supporting document is to provide traceability and a Quality Assurance record for future reference to these packages

  4. Exposure to a dog elicits different cardiovascular and behavioral effects in pregnant and lactating goats

    OpenAIRE

    Olsson Kerstin; Hydbring-Sandberg Eva

    2011-01-01

    Abstract Background Heart rate and plasma cortisol concentration are often used in evaluation of physiological reactions to stress and fear, but arterial blood pressure is rarely measured in farm animals. Goats are prey animals and can be expected to react strongly to a predator, especially when they have kids. We hypothesized that exposure to a dog elicits a flight response during pregnancy and a fight response when goats have kids to defend. Arterial blood pressure and heart rate should inc...

  5. The influence of the ratio bias phenomenon on the elicitation of health states utilities

    Directory of Open Access Journals (Sweden)

    Jose-Luis Pinto-Prades

    2006-11-01

    Full Text Available This paper tests whether logically equivalent risk formats can lead to different health state utilities elicited by means of the traditional standard gamble (SG method and a modified version of the method that we call ``double lottery.'' We compare utilities for health states elicited when probabilities are framed in terms of frequencies with respect to 100 people in the population (i.e., X out of 100 who follow a medical treatment will die with SG utilities elicited for frequencies with respect to 1,000 people in the population (i.e., Y out of 1,000 who follow a medical treatment will die. We found that people accepted a lower risk of death when success and failure probabilities were framed as frequencies type ``Y deaths out of 1,000'' rather than as frequencies type ``X deaths out of 100'' and hence the utilities for health outcomes were higher when the denominator was 1000 than when it was 100. This framing effect, known as Ratio Bias, may have important consequences in resource allocation decisions.

  6. Quantification of the Impact of the HIV-1-Glycan Shield on Antibody Elicitation

    Directory of Open Access Journals (Sweden)

    Tongqing Zhou

    2017-04-01

    Full Text Available While the HIV-1-glycan shield is known to shelter Env from the humoral immune response, its quantitative impact on antibody elicitation has been unclear. Here, we use targeted deglycosylation to measure the impact of the glycan shield on elicitation of antibodies against the CD4 supersite. We engineered diverse Env trimers with select glycans removed proximal to the CD4 supersite, characterized their structures and glycosylation, and immunized guinea pigs and rhesus macaques. Immunizations yielded little neutralization against wild-type viruses but potent CD4-supersite neutralization (titers 1: >1,000,000 against four-glycan-deleted autologous viruses with over 90% breadth against four-glycan-deleted heterologous strains exhibiting tier 2 neutralization character. To a first approximation, the immunogenicity of the glycan-shielded protein surface was negligible, with Env-elicited neutralization (ID50 proportional to the exponential of the protein-surface area accessible to antibody. Based on these high titers and exponential relationship, we propose site-selective deglycosylated trimers as priming immunogens to increase the frequency of site-targeting antibodies.

  7. Photo-elicitation in lifelong learning of teachers of elementary education

    Directory of Open Access Journals (Sweden)

    Antonio Bautista García-Vera

    2017-07-01

    Full Text Available In this article we present and analyze a plan of teacher training. This plan is promoted and supported in the photographs taken by two teachers in their classrooms. Subsequently, through two focus groups, one for each class, we reflect and debate on the content of the photographs. This study is based on three areas of theorizing: teacher reflection on own practice, the essence of experiential image and multimodal literacy of teacher and, finally, the value of the photo- elicitation as a means of storytelling. The question generator that plan was how to materialize represent delayed or experiential image of the teacher to encourage description and, therefore, understanding the experiences of your practice? The response we obtained using photo - elicitation is helping us to further investigate with rigor in human experiences unrelated to the hegemonic visual communication methodologies. Among its benefits within the teacher training, is to recreate the action out of what happened in it and, in parallel, offering the possibility of making visible and discuss conflicts and ethical dilemmas present in it. Thus, the photo- elicitation situations are warm to analyze how and why a teacher has made a decision and no other, because when asked by a choice made is forced to explain his theories, beliefs, values, attitudes.., and only when made explicit, when subjected to public scrutiny, is aware of them. We note that the change in teachers is only possible when it is aware of his theories, beliefs ... and what they entail in teaching.

  8. Brain-heart linear and nonlinear dynamics during visual emotional elicitation in healthy subjects.

    Science.gov (United States)

    Valenza, G; Greco, A; Gentili, C; Lanata, A; Toschi, N; Barbieri, R; Sebastiani, L; Menicucci, D; Gemignani, A; Scilingo, E P

    2016-08-01

    This study investigates brain-heart dynamics during visual emotional elicitation in healthy subjects through linear and nonlinear coupling measures of EEG spectrogram and instantaneous heart rate estimates. To this extent, affective pictures including different combinations of arousal and valence levels, gathered from the International Affective Picture System, were administered to twenty-two healthy subjects. Time-varying maps of cortical activation were obtained through EEG spectral analysis, whereas the associated instantaneous heartbeat dynamics was estimated using inhomogeneous point-process linear models. Brain-Heart linear and nonlinear coupling was estimated through the Maximal Information Coefficient (MIC), considering EEG time-varying spectra and point-process estimates defined in the time and frequency domains. As a proof of concept, we here show preliminary results considering EEG oscillations in the θ band (4-8 Hz). This band, indeed, is known in the literature to be involved in emotional processes. MIC highlighted significant arousal-dependent changes, mediated by the prefrontal cortex interplay especially occurring at intermediate arousing levels. Furthermore, lower and higher arousing elicitations were associated to not significant brain-heart coupling changes in response to pleasant/unpleasant elicitations.

  9. The perspective awareness model - Eliciting multiple perspectives to formulate high quality decisions

    International Nuclear Information System (INIS)

    Boucher, Laurel

    2013-01-01

    A great deal of attention is given to the importance of communication in environmental remediation and radioactive waste management. However, very little attention is given to eliciting multiple perspectives so as to formulate high quality decisions. Plans that are based on a limited number of perspectives tend to be narrowly focused whereas those that are based on a wide variety of perspectives tend to be comprehensive, higher quality, and more apt to be put into application. In addition, existing methods of dialogue have built-in limitations in that they typically draw from the predominant thinking patterns which focus in some areas but ignore others. This can result in clarity but a lack of comprehensiveness. This paper presents a Perspective Awareness Model which helps groups such as partnering teams, interagency teams, steering committees, and working groups elicit a wide net of perspectives and viewpoints. The paper begins by describing five factors that makes cooperation among such groups challenging. Next, a Perspective Awareness Model that makes it possible to manage these five factors is presented. The two primary components of this model --- the eight 'Thinking Directions' and the 'Shared Documentation' --- are described in detail. Several examples are given to illustrate how the Perspective Awareness Model can be used to elicit multiple perspectives to formulate high quality decisions in the area of environmental remediation and radioactive waste management. (authors)

  10. Dopamine D4 receptor polymorphism modulates cue-elicited heroin craving in Chinese.

    Science.gov (United States)

    Shao, Chunhong; Li, Yifeng; Jiang, Kaida; Zhang, Dandan; Xu, Yifeng; Lin, Ling; Wang, Qiuying; Zhao, Min; Jin, Li

    2006-06-01

    Subjective craving, which contributes to the continuation of drug use in active abuser and the occurrence of relapse in detoxified abusers, is considered to be a central phenomenon in addiction. Dopamine pathway has been implicated in the mechanism underlying the cue-elicited craving for a variety of addictive substances. The objective of this study was to test the hypothesis that heroin addicts carrying D4 dopamine receptor gene (DRD4) variable number tandem repeat (VNTR) long type allele would have higher craving after exposure to a heroin-related cue. Craving was induced by a series of exposure to neutral and heroin-related cue and were assessed in a cohort of Chinese heroin abusers (n=420) recruited from the Voluntary Drug Dependence Treatment Center at Shanghai. Significantly stronger cue-elicited heroin craving was found in individuals carrying DRD4 VNTR long type allele than the non-carriers (F=31.040, pcue-elicited craving in heroin dependence, indicating DRD4 VNTR represents one of potential genetic risk factors for cue-induced craving.

  11. Eliciting hyperparameters of prior distributions for the parameters of paired comparison models

    Directory of Open Access Journals (Sweden)

    Nasir Abbas

    2013-02-01

    Full Text Available Normal 0 false false false EN-US X-NONE AR-SA In the study of paired comparisons (PC, items may be ranked or issues may be prioritized through subjective assessment of certain judges. PC models are developed and then used to serve the purpose of ranking. The PC models may be studied through classical or Bayesian approach. Bayesian inference is a modern statistical technique used to draw conclusions about the population parameters. Its beauty lies in incorporating prior information about the parameters into the analysis in addition to current information (i.e. data. The prior and current information are formally combined to yield a posterior distribution about the population parameters, which is the work bench of the Bayesian statisticians. However, the problems the Bayesians face correspond to the selection and formal utilization of prior distribution. Once the type of prior distribution is decided to be used, the problem of estimating the parameters of the prior distribution (i.e. elicitation still persists. Different methods are devised to serve the purpose. In this study an attempt is made to use Minimum Chi-square (hence forth MCS for the elicitation purpose. Though it is a classical estimation technique, but is used here for the election purpose. The entire elicitation procedure is illustrated through a numerical data set.

  12. Expert elicitation, uncertainty, and the value of information in controlling invasive species

    Science.gov (United States)

    Johnson, Fred A.; Smith, Brian J.; Bonneau, Mathieu; Martin, Julien; Romagosa, Christina; Mazzotti, Frank J.; Waddle, J. Hardin; Reed, Robert; Eckles, Jennifer Kettevrlin; Vitt, Laurie J.

    2017-01-01

    We illustrate the utility of expert elicitation, explicit recognition of uncertainty, and the value of information for directing management and research efforts for invasive species, using tegu lizards (Salvator merianae) in southern Florida as a case study. We posited a post-birth pulse, matrix model in which four age classes of tegus are recognized: hatchlings, 1 year-old, 2 year-olds, and 3 + year-olds. This matrix model was parameterized using a 3-point process to elicit estimates of tegu demographic rates in southern Florida from 10 herpetology experts. We fit statistical distributions for each parameter and for each expert, then drew and pooled a large number of replicate samples from these to form a distribution for each demographic parameter. Using these distributions, as well as the observed correlations among elicited values, we generated a large sample of matrix population models to infer how the tegu population would respond to control efforts. We used the concepts of Pareto efficiency and stochastic dominance to conclude that targeting older age classes at relatively high rates appears to have the best chance of minimizing tegu abundance and control costs. We conclude that expert opinion combined with an explicit consideration of uncertainty can be valuable in conducting an initial assessment of what control strategy, effort, and monetary resources are needed to reduce and eventually eliminate the invader. Scientists, in turn, can use the value of information to focus research in a way that not only increases the efficacy of control, but minimizes costs as well.

  13. Eliciting Patients’ Health Concerns in Consulting Rooms and Wards in Vietnamese Public Hospitals

    Directory of Open Access Journals (Sweden)

    Huong Thi Linh Nguyen

    2018-03-01

    Full Text Available This article examines the doctor’s elicitation of the patient’s presenting health concern in two clinical settings in the Vietnamese public hospital system: the consulting room and the ward. The data were taken from 66 audio-recorded consultations. Our analysis shows that the elicitors used by the doctor in the consulting room often communicate a weak epistemic stance towards the patient’s health issue, while those used in the ward tend to signal a strong epistemic stance. In addition, this contrast between the elicitors employed in the consulting room and the ward is evident in our data regardless of whether the consultation is a first visit or a same follow-up (in which the doctor is the same one that treated the patient on their last visit, though the contrast is less clear for different follow-ups (in which the doctor has not treated the patient before. An additional finding is that the clinical setting has some bearing on the use of inappropriate elicitation formats (in which the doctor opens the visit with an elicitor which is more appropriate for another type of visit. The precise way in which each of the consulting room and the ward operates is, of course, a feature of the Vietnamese public hospital system itself. Hence, the overall contrast between the elicitors and elicitation formats used in these two settings illustrates how, on a more general level, the institutional context can have an impact on doctor-patient communication.

  14. Analysis of creative mathematical thinking ability by using model eliciting activities (MEAs)

    Science.gov (United States)

    Winda, A.; Sufyani, P.; Elah, N.

    2018-05-01

    Lack of creative mathematical thinking ability can lead to not accustomed with open ended problem. Students’ creative mathematical thinking ability in the first grade at one of junior high school in Tangerang City is not fully developed. The reason of students’ creative mathematical thinking ability is not optimally developed is so related with learning process which has done by the mathematics teacher, maybe the learning design that teacher use is unsuitable for increasing students’ activity in the learning process. This research objective is to see the differences in students’ ways of answering the problems in terms of students’ creative mathematical thinking ability during the implementation of Model Eliciting Activities (MEAs). This research use post-test experimental class design. The indicators for creative mathematical thinking ability in this research arranged in three parts, as follow: (1) Fluency to answer the problems; (2) Flexibility to solve the problems; (3) Originality of answers. The result of this research found that by using the same learning model and same instrument from Model Eliciting Activities (MEAs) there are some differences in the way students answer the problems and Model Eliciting Activities (MEAs) can be one of approach used to increase students’ creative mathematical thinking ability.

  15. High spatial validity is not sufficient to elicit voluntary shifts of attention.

    Science.gov (United States)

    Pauszek, Joseph R; Gibson, Bradley S

    2016-10-01

    Previous research suggests that the use of valid symbolic cues is sufficient to elicit voluntary shifts of attention. The present study interpreted this previous research within a broader theoretical context which contends that observers will voluntarily use symbolic cues to orient their attention in space when the temporal costs of using the cues are perceived to be less than the temporal costs of searching without the aid of the cues. In this view, previous research has not addressed the sufficiency of valid symbolic cues, because the temporal cost of using the cues is usually incurred before the target display appears. To address this concern, 70%-valid spatial word cues were presented simultaneously with a search display. In addition, other research suggests that opposing cue-dependent and cue-independent spatial biases may operate in these studies and alter standard measures of orienting. After identifying and controlling these opposing spatial biases, the results of two experiments showed that the word cues did not elicit voluntary shifts of attention when the search task was relatively easy but did when the search task was relatively difficult. Moreover, the findings also showed that voluntary use of the word cues changed over the course of the experiment when the task was difficult, presumably because the temporal cost of searching without the cue lessened as the task got easier with practice. Altogether, the present findings suggested that the factors underlying voluntary control are multifaceted and contextual, and that spatial validity alone is not sufficient to elicit voluntary shifts of attention.

  16. Real-Time Elicitation of Moral Emotions Using a Prejudice Paradigm

    Science.gov (United States)

    Fourie, Melike M.; Kilchenmann, Nadine; Malcolm-Smith, Susan; Thomas, Kevin G. F. 

    2012-01-01

    Moral emotions are critically important in guiding appropriate social conduct. Empirical investigation of these emotions remains a challenge, however, because of the difficulty in eliciting them reliably in controlled settings. Here we describe a novel prejudice paradigm that aimed to elicit both negatively and positively valenced moral emotions in real-time. Low-prejudice females (N = 46) who met highly specific demographic and personality-based screening criteria completed a series of Implicit Association Tests (IATs). Feedback following these IATs was pre-programmed to either endorse participants’ non-prejudiced self-standards (positive condition), or to contradict their self-standards (negative condition), in response to sensitive social topics. Neutral condition IATs reflected participants’ attitudes toward non-sensitive social topics. Results demonstrated that the IATs were successful in eliciting moral-positive emotions (satisfaction and pride) and moral-negative emotions (primarily guilt). In addition, participants high in self-reported punishment sensitivity, as assessed by the Behavioral Inhibition System (BIS) scale, reported greater guilt. PMID:22888322

  17. Quantification of the Impact of the HIV-1-Glycan Shield on Antibody Elicitation

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, Tongqing; Doria-Rose, Nicole A.; Cheng, Cheng; Stewart-Jones, Guillaume B. E.; Chuang, Gwo-Yu; Chambers, Michael; Druz, Aliaksandr; Geng, Hui; McKee, Krisha; Kwon, Young Do; O’Dell, Sijy; Sastry, Mallika; Schmidt, Stephen D.; Xu, Kai; Chen, Lei; Chen, Rita E.; Louder, Mark K.; Pancera, Marie; Wanninger, Timothy G.; Zhang, Baoshan; Zheng, Anqi; Farney, S. Katie; Foulds, Kathryn E.; Georgiev, Ivelin S.; Joyce, M. Gordon; Lemmin, Thomas; Narpala, Sandeep; Rawi, Reda; Soto, Cinque; Todd, John-Paul; Shen, Chen-Hsiang; Tsybovsky, Yaroslav; Yang, Yongping; Zhao, Peng; Haynes, Barton F.; Stamatatos, Leonidas; Tiemeyer, Michael; Wells, Lance; Scorpio, Diana G.; Shapiro, Lawrence; McDermott, Adrian B.; Mascola, John R.; Kwong, Peter D.

    2017-04-01

    While the HIV-1-glycan shield is known to shelter Env from the humoral immune response, its quantitative impact on antibody elicitation has been unclear. Here, we use targeted deglycosylation to measure the impact of the glycan shield on elicitation of antibodies against the CD4 supersite. We engineered diverse Env trimers with select glycans removed proximal to the CD4 supersite, characterized their structures and glycosylation, and immunized guinea pigs and rhesus macaques. Immunizations yielded little neutralization against wild-type viruses but potent CD4-supersite neutralization (titers 1: >1,000,000 against four-glycan-deleted autologous viruses with over 90% breadth against four-glycan-deleted heterologous strains exhibiting tier 2 neutralization character). To a first approximation, the immunogenicity of the glycan-shielded protein surface was negligible, with Env-elicited neutralization (ID50) proportional to the exponential of the protein-surface area accessible to antibody. Based on these high titers and exponential relationship, we propose site-selective deglycosylated trimers as priming immunogens to increase the frequency of site-targeting antibodies.

  18. Elicitation of expert prior opinion: application to the MYPAN trial in childhood polyarteritis nodosa.

    Directory of Open Access Journals (Sweden)

    Lisa V Hampson

    Full Text Available Definitive sample sizes for clinical trials in rare diseases are usually infeasible. Bayesian methodology can be used to maximise what is learnt from clinical trials in these circumstances. We elicited expert prior opinion for a future Bayesian randomised controlled trial for a rare inflammatory paediatric disease, polyarteritis nodosa (MYPAN, Mycophenolate mofetil for polyarteritis nodosa.A Bayesian prior elicitation meeting was convened. Opinion was sought on the probability that a patient in the MYPAN trial treated with cyclophosphamide would achieve disease remission within 6-months, and on the relative efficacies of mycophenolate mofetil and cyclophosphamide. Expert opinion was combined with previously unseen data from a recently completed randomised controlled trial in ANCA associated vasculitis.A pan-European group of fifteen experts participated in the elicitation meeting. Consensus expert prior opinion was that the most likely rates of disease remission within 6 months on cyclophosphamide or mycophenolate mofetil were 74% and 71%, respectively. This prior opinion will now be taken forward and will be modified to formulate a Bayesian posterior opinion once the MYPAN trial data from 40 patients randomised 1:1 to either CYC or MMF become available.We suggest that the methodological template we propose could be applied to trial design for other rare diseases.

  19. Mirth and laughter elicited by electrical stimulation of the human anterior cingulate cortex.

    Science.gov (United States)

    Caruana, Fausto; Avanzini, Pietro; Gozzo, Francesca; Francione, Stefano; Cardinale, Francesco; Rizzolatti, Giacomo

    2015-10-01

    Laughter is a complex motor behavior that, typically, expresses mirth. Despite its fundamental role in social life, knowledge about the neural basis of laughter is very limited and mostly based on a few electrical stimulation (ES) studies carried out in epileptic patients. In these studies laughter was elicited from temporal areas where it was accompanied by mirth and from frontal areas plus an anterior cingulate case where laughter without mirth was observed. On the basis of these findings, it has been proposed a dichotomy between temporal lobe areas processing the emotional content of laughter and anterior cingulate cortex (ACC) and motor areas responsible of laughter production. The present study is aimed to understand the role of ACC in laughter. We report the effects of stimulation of 10 rostral, pregenual ACC (pACC) patients in which the ES elicited laughter. In half of the patients ES elicited a clear burst of laughter with mirth, while in the other half mirth was not evident. This large dataset allow us to offer a more reliable picture of the functional contribute of this region in laughter, and to precisely localize it in the cingulate cortex. We conclude that the pACC is involved in both the motor and the affective components of emotions, and challenge the validity of a sharp dichotomy between motor and emotional centers for laughing. Finally, we suggest a possible anatomical network for the production of positive emotional expressions. Copyright © 2015 Elsevier Ltd. All rights reserved.

  20. Memory-based pre-attentive auditory N1 elicited by sound movement.

    Science.gov (United States)

    Ohoyama, Keiko; Motomura, Eishi; Inui, Koji; Nishihara, Makoto; Otsuru, Naofumi; Oi, Motoyasu; Kakigi, Ryusuke; Okada, Motohiro

    2012-07-01

    Quickly detecting changes in the surrounding environment is one of the most important functions of sensory processing. Comparison of a new event with preceding sensory conditions is necessary for the change-detection process. A sudden change in a continuous sound elicits auditory evoked potentials that peak approximately 100 ms after the onset of the change (Change-N1). In the present study, we recorded Change-N1 under an oddball paradigm in 19 healthy subjects using an abruptly moving sound (SM-stimulus) as a deviant stimulus and investigated effects of the probability of the SM-stimulus to reveal whether Change-N1 is a memory-based response. We compared the amplitude and latency of Change-N1 elicited by the SM-stimulus among three probability conditions (33, 50 and 100%). As the probability of the SM-stimulus decreased, the amplitude of Change-N1 increased and its latency decreased. The present results indicate that the preceding sensory history affects Change-N1 elicited by the SM-stimulus. Copyright © 2012 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

  1. Real-time elicitation of moral emotions using a prejudice paradigm.

    Directory of Open Access Journals (Sweden)

    Melike Marethe Fourie

    2012-08-01

    Full Text Available Moral emotions are critically important in guiding appropriate social conduct. Empirical investigation of these emotions remains a challenge, however, because of the difficulty in eliciting them reliably in controlled settings. Here we describe a novel prejudice paradigm that aimed to elicit both negatively- and positively-valenced moral emotions in real-time. Low-prejudice females (N = 46 who met highly specific demographic and personality-based screening criteria completed a series of Implicit Association Tests (IATs. Feedback following these IATs was pre-programmed to either endorse participants’ nonprejudiced self-standards (positive condition, or to contradict their self-standards (negative condition, in response to sensitive social topics. Neutral condition IATs reflected participants’ attitudes toward non-sensitive social topics. Results demonstrated that the IATs were successful in eliciting moral-positive emotions (satisfaction and pride, and moral-negative emotions (primarily guilt. In addition, participants high in self-reported punishment sensitivity, as assessed by the Behavioral Inhibition System (BIS scale, reported greater guilt.

  2. Real-time elicitation of moral emotions using a prejudice paradigm.

    Science.gov (United States)

    Fourie, Melike M; Kilchenmann, Nadine; Malcolm-Smith, Susan; Thomas, Kevin G F

    2012-01-01

    Moral emotions are critically important in guiding appropriate social conduct. Empirical investigation of these emotions remains a challenge, however, because of the difficulty in eliciting them reliably in controlled settings. Here we describe a novel prejudice paradigm that aimed to elicit both negatively and positively valenced moral emotions in real-time. Low-prejudice females (N = 46) who met highly specific demographic and personality-based screening criteria completed a series of Implicit Association Tests (IATs). Feedback following these IATs was pre-programmed to either endorse participants' non-prejudiced self-standards (positive condition), or to contradict their self-standards (negative condition), in response to sensitive social topics. Neutral condition IATs reflected participants' attitudes toward non-sensitive social topics. Results demonstrated that the IATs were successful in eliciting moral-positive emotions (satisfaction and pride) and moral-negative emotions (primarily guilt). In addition, participants high in self-reported punishment sensitivity, as assessed by the Behavioral Inhibition System (BIS) scale, reported greater guilt.

  3. Oncolytic Immunotherapy: Dying the Right Way is a Key to Eliciting Potent Antitumor Immunity

    Directory of Open Access Journals (Sweden)

    Zong Sheng eGuo

    2014-04-01

    Full Text Available Oncolytic viruses (OVs are novel immunotherapeutic agents whose anticancer effects come from both oncolysis and elicited antitumor immunity. OVs induce mostly immunogenic cancer cell death (ICD, including immunogenic apoptosis, necrosis/necroptosis, pyroptosis and autophagic cell death, leading to exposure of calreticulin and heat-shock proteins to the cell surface, and/or released ATP, high mobility group box-1 [HMGB1], uric acid, and other DAMPs as well as PAMPs as danger signals, along with tumor-associated antigens, to activate dendritic cells (DCs and elicit adaptive antitumor immunity. Dying the right way may greatly potentiate adaptive antitumor immunity. The mode of cancer cell death may be modulated by individual OVs and cancer cells as they often encode and express genes that inhibit/promote apoptosis, necroptosis or autophagic cell death. We can genetically engineer OVs with death-pathway-modulating genes and thus skew the infected cancer cells towards certain death pathways for the enhanced immunogenicity. Strategies combining with some standard therapeutic regimens may also change the immunological consequence of cancer cell death. In this review, we discuss recent advances in our understanding of danger signals, modes of cancer cell death induced by OVs, the induced danger signals and functions in eliciting subsequent antitumor immunity. We also discuss potential combination strategies to target cells into specific modes of ICD and enhance cancer immunogenicity, including blockade of immune checkpoints, in order to break immune tolerance, improve antitumor immunity and thus the overall therapeutic efficacy.

  4. Eliciting geologists' tacit model of the uncertainty of mapped geological boundaries

    Science.gov (United States)

    Lark, R. M.; Lawley, R. S.; Barron, A. J. M.; Aldiss, D. T.; Ambrose, K.; Cooper, A. H.; Lee, J. R.; Waters, C. N.

    2015-01-01

    It is generally accepted that geological linework, such as mapped boundaries, are uncertain for various reasons. It is difficult to quantify this uncertainty directly, because the investigation of error in a boundary at a single location may be costly and time consuming, and many such observations are needed to estimate an uncertainty model with confidence. However, it is also recognized across many disciplines that experts generally have a tacit model of the uncertainty of information that they produce (interpretations, diagnoses etc.) and formal methods exist to extract this model in usable form by elicitation. In this paper we report a trial in which uncertainty models for mapped boundaries in six geological scenarios were elicited from a group of five experienced geologists. In five cases a consensus distribution was obtained, which reflected both the initial individually elicted distribution and a structured process of group discussion in which individuals revised their opinions. In a sixth case a consensus was not reached. This concerned a boundary between superficial deposits where the geometry of the contact is hard to visualize. The trial showed that the geologists' tacit model of uncertainty in mapped boundaries reflects factors in addition to the cartographic error usually treated by buffering linework or in written guidance on its application. It suggests that further application of elicitation, to scenarios at an appropriate level of generalization, could be useful to provide working error models for the application and interpretation of linework.

  5. Exposure to the taste of alcohol elicits activation of the mesocorticolimbic neurocircuitry.

    Science.gov (United States)

    Filbey, Francesca M; Claus, Eric; Audette, Amy R; Niculescu, Michelle; Banich, Marie T; Tanabe, Jody; Du, Yiping P; Hutchison, Kent E

    2008-05-01

    A growing number of imaging studies suggest that alcohol cues, mainly visual, elicit activation in mesocorticolimbic structures. Such findings are consistent with the growing recognition that these structures play an important role in the attribution of incentive salience and the pathophysiology of addiction. The present study investigated whether the presentation of alcohol taste cues can activate brain regions putatively involved in the acquisition and expression of incentive salience. Using functional magnetic resonance imaging, we recorded BOLD activity while delivering alcoholic tastes to 37 heavy drinking but otherwise healthy volunteers. The results yielded a pattern of BOLD activity in mesocorticolimbic structures (ie prefrontal cortex, striatum, ventral tegmental area/substantia nigra) relative to an appetitive control. Further analyses suggested strong connectivity between these structures during cue-elicited urge and demonstrated significant positive correlations with a measure of alcohol use problems (ie the Alcohol Use Disorders Identification Test). Thus, repeated exposure to the taste alcohol in the scanner elicits activation in mesocorticolimbic structures, and this activation is related to measures of urge and severity of alcohol problems.

  6. Effects of adjuvants on IgG subclasses elicited by virus-like Particles

    Directory of Open Access Journals (Sweden)

    Visciano Maria Luisa

    2012-01-01

    Full Text Available Abstract Background Virus-Like Particles (VLPs represent an efficient strategy to present and deliver conformational antigens to the immune system, inducing both arms of the adaptive immune response. Moreover, their particulate structure surrounded by cell membrane provides an adjuvanted effect to VLP-based immunizations. In the present study, the elicitation of different patterns of IgG subclasses by VLPs, administered in CpG ODN1826 or poly(I:C adjuvants, has been evaluated in an animal model. Results Adjuvanted VLPs elicited a higher titer of total specific IgG compared to VLPs alone. Furthermore, while VLPs alone induced a balanced TH2 pattern, VLPs formulated with either adjuvant elicited a TH1-biased IgG subclasses (IgG2a and IgG3, with poly(I:C more potent than CpG ODN1826. Conclusions The results confirmed that adjuvants efficiently improve antigen immunogenicity and represent a suitable strategy to skew the adaptive immune response toward the differentiation of the desired T helper subset, also using VLPs as antigen.

  7. Eliciting, Identifying, Interpreting, and Responding to Students' Ideas: Teacher Candidates' Growth in Formative Assessment Practices

    Science.gov (United States)

    Gotwals, Amelia Wenk; Birmingham, Daniel

    2016-06-01

    With the goal of helping teacher candidates become well-started beginners, it is important that methods courses in teacher education programs focus on high-leverage practices. Using responsive teaching practices, specifically eliciting, identifying, interpreting, and responding to students' science ideas (i.e., formative assessment), can be used to support all students in learning science successfully. This study follows seven secondary science teacher candidates in a yearlong practice-based methods course. Course assignments (i.e., plans for and reflections on teaching) as well as teaching videos were analyzed using a recursive qualitative approach. In this paper, we present themes and patterns in teacher candidates' abilities to elicit, identify, interpret, and respond to students' ideas. Specifically, we found that those teacher candidates who grew in the ways in which they elicited students' ideas from fall to spring were also those who were able to adopt a more balanced reflection approach (considering both teacher and student moves). However, we found that even the teacher candidates who grew in these practices did not move toward seeing students' ideas as nuanced; rather, they saw students' ideas in a dichotomous fashion: right or wrong. We discuss implications for teacher preparation, specifically for how to promote productive reflection and tools for better understanding students' ideas.

  8. A structured review of health utility measures and elicitation in advanced/metastatic breast cancer

    Directory of Open Access Journals (Sweden)

    Hao Y

    2016-06-01

    Full Text Available Yanni Hao,1 Verena Wolfram,2 Jennifer Cook2 1Novartis Pharmaceuticals, East Hanover, NJ, USA; 2Adelphi Values, Bollington, UK Background: Health utilities are increasingly incorporated in health economic evaluations. Different elicitation methods, direct and indirect, have been established in the past. This study examined the evidence on health utility elicitation previously reported in advanced/metastatic breast cancer and aimed to link these results to requirements of reimbursement bodies. Methods: Searches were conducted using a detailed search strategy across several electronic databases (MEDLINE, EMBASE, Cochrane Library, and EconLit databases, online sources (Cost-effectiveness Analysis Registry and the Health Economics Research Center, and web sites of health technology assessment (HTA bodies. Publications were selected based on the search strategy and the overall study objectives. Results: A total of 768 publications were identified in the searches, and 26 publications, comprising 18 journal articles and eight submissions to HTA bodies, were included in the evidence review. Most journal articles derived utilities from the European Quality of Life Five-Dimensions questionnaire (EQ-5D. Other utility measures, such as the direct methods standard gamble (SG, time trade-off (TTO, and visual analog scale (VAS, were less frequently used. Several studies described mapping algorithms to generate utilities from disease-specific health-related quality of life (HRQOL instruments such as European Organization for Research and Treatment of Cancer Quality of Life Questionnaire – Core 30 (EORTC QLQ-C30, European Organization for Research and Treatment of Cancer Quality of Life Questionnaire – Breast Cancer 23 (EORTC QLQ-BR23, Functional Assessment of Cancer Therapy – General questionnaire (FACT-G, and Utility-Based Questionnaire-Cancer (UBQ-C; most used EQ-5D as the reference. Sociodemographic factors that affect health utilities, such as age, sex

  9. A structured review of health utility measures and elicitation in advanced/metastatic breast cancer.

    Science.gov (United States)

    Hao, Yanni; Wolfram, Verena; Cook, Jennifer

    2016-01-01

    Health utilities are increasingly incorporated in health economic evaluations. Different elicitation methods, direct and indirect, have been established in the past. This study examined the evidence on health utility elicitation previously reported in advanced/metastatic breast cancer and aimed to link these results to requirements of reimbursement bodies. Searches were conducted using a detailed search strategy across several electronic databases (MEDLINE, EMBASE, Cochrane Library, and EconLit databases), online sources (Cost-effectiveness Analysis Registry and the Health Economics Research Center), and web sites of health technology assessment (HTA) bodies. Publications were selected based on the search strategy and the overall study objectives. A total of 768 publications were identified in the searches, and 26 publications, comprising 18 journal articles and eight submissions to HTA bodies, were included in the evidence review. Most journal articles derived utilities from the European Quality of Life Five-Dimensions questionnaire (EQ-5D). Other utility measures, such as the direct methods standard gamble (SG), time trade-off (TTO), and visual analog scale (VAS), were less frequently used. Several studies described mapping algorithms to generate utilities from disease-specific health-related quality of life (HRQOL) instruments such as European Organization for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 (EORTC QLQ-C30), European Organization for Research and Treatment of Cancer Quality of Life Questionnaire - Breast Cancer 23 (EORTC QLQ-BR23), Functional Assessment of Cancer Therapy - General questionnaire (FACT-G), and Utility-Based Questionnaire-Cancer (UBQ-C); most used EQ-5D as the reference. Sociodemographic factors that affect health utilities, such as age, sex, income, and education, as well as disease progression, choice of utility elicitation method, and country settings, were identified within the journal articles. Most

  10. Risk-Informed SSCs Categorization: Elicitation Method of Expert's Opinion

    Energy Technology Data Exchange (ETDEWEB)

    Hwang, Mee Jeong; Yang, Joon Eon; Kim, Kil Yoo

    2005-01-15

    The regulations have been performing by deterministic way since nuclear power plants have been operating. However, some SSCs identified as safety-significance by deterministic way, were turned out to be low or non safety-significant and some SSCs identified as non-safety significance were turned out to be high safety-significant according to the results of PSA. Considering these risk insights, Regulatory Guide 1.174 and 10CFR50.69 were drawn up, and we can re-categorize the SSCs according to their safety significance. Therefore, a study and an interest about the risk-informed SSCs re-categorization and treatment has been continued. The objective of this regulatory initiative is to adjust the scope of equipment subject to special regulatory treatment to better focus licensee and regulatory attention and resources on equipment that has safety significance. Current most regulations define the plant equipment necessary to meet deterministic regulatory basis as 'safety-related.' This equipment is subject to special treatment regulations. Other plant equipment is categorized as 'non-safety related,' and is not subject to a select number of special treatment requirement or a subset of those requirement. However, risk information is not a magic tool making a decision but a supporting tool to categorize SSCs. This is because only small parts of a plant are modeled in PSA model. Thus, engineering and deterministic judgments are also used for risk-informed SSCs categorization, and expert opinion elicitation is very important for risk-informed SSCs categorization. Therefore, we need a rational method to elicit the expert's opinions, and in this study, we developed a systematic method for expert elicitation to categorize the nuclear power plants' SSCs. Current states for SSCs categorization of the USA and the existing methods for expert elicitation were surveyed and more systematic way eliciting the expert opinions and combining was developed. To

  11. Exercise Lowers Threshold and Increases Severity, but Wheat-Dependent, Exercise-Induced Anaphylaxis Can Be Elicited at Rest

    DEFF Research Database (Denmark)

    Christensen, Morten J.; Eller, Esben; Mortz, Charlotte G.

    2018-01-01

    of specific IgE (sIgE) were followed by an oral food challenge with gluten at rest and in combination with treadmill exercise. Results: A clinical reaction was elicited in 47 of 71 (66%), and in 26 of these (37%) the reaction could be elicited at rest. The median dose required at rest was 48 g (8-80 g...... with exercise. Conclusions: A challenge test with gluten at rest and combined exercise is a safe confirmatory test for WDEIA. A reaction can be elicited at rest (without exercise), but exercise is able to lower the threshold and increase the severity....

  12. Group elicitations yield more consistent, yet more uncertain experts in understanding risks to ecosystem services in New Zealand bays

    KAUST Repository

    Singh, Gerald G.; Sinner, Jim; Ellis, Joanne; Kandlikar, Milind; Halpern, Benjamin S.; Satterfield, Terre; Chan, Kai

    2017-01-01

    The elicitation of expert judgment is an important tool for assessment of risks and impacts in environmental management contexts, and especially important as decision-makers face novel challenges where prior empirical research is lacking or insufficient. Evidence-driven elicitation approaches typically involve techniques to derive more accurate probability distributions under fairly specific contexts. Experts are, however, prone to overconfidence in their judgements. Group elicitations with diverse experts can reduce expert overconfidence by allowing cross-examination and reassessment of prior judgements, but groups are also prone to uncritical

  13. Group elicitations yield more consistent, yet more uncertain experts in understanding risks to ecosystem services in New Zealand bays

    KAUST Repository

    Singh, Gerald G.

    2017-08-02

    The elicitation of expert judgment is an important tool for assessment of risks and impacts in environmental management contexts, and especially important as decision-makers face novel challenges where prior empirical research is lacking or insufficient. Evidence-driven elicitation approaches typically involve techniques to derive more accurate probability distributions under fairly specific contexts. Experts are, however, prone to overconfidence in their judgements. Group elicitations with diverse experts can reduce expert overconfidence by allowing cross-examination and reassessment of prior judgements, but groups are also prone to uncritical

  14. Effects of Elicited Reflections combined with Tutor or Peer Feedback on Self-Regulated Learning and Learning Outcomes

    NARCIS (Netherlands)

    Van den Boom, Gerard; Paas, Fred; Van Merriënboer, Jeroen

    2009-01-01

    Van den Boom, G., Paas, F., & Van Merriënboer, J. J. G. (2007). Effects of elicited reflections combined with tutor or peer feedback on self-regulated learning and learning outcomes. Learning and Instruction, 17, 532-548.

  15. Using Psychophysiological Measures to Examine the Temporal Profile of Verbal Humor Elicitation.

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    Chris M Fiacconi

    Full Text Available Despite its pervasiveness in popular culture, there remains much to be learned about the psychological and physiological processes that underlie our experience of humor. In the present study, we examined the temporal profile of verbal humor elicitation using psychophysiological measures of heart rate (HR and facial electromyography (EMG. Consistent with recent prior research on cardiovascular changes to perceived humor, we found that HR acceleration was greater for jokes relative to non-jokes, and was positively related to the level of perceived humor elicited by these jokes. In addition, activity recorded from the zygomaticus major muscle that controls smiling was found to be greater for jokes relative to non-jokes. To link these physiological changes to the psychological processes that govern humor comprehension, we took the initial inflection point of the zygomatic EMG response as a marker for the onset of humor comprehension, and used this marker to probe the pattern of cardiovascular activity at this time-point. We estimated the onset of the humor response to occur during the initial HR deceleration phase, and found that jokes relative to non-jokes elicited a decreased HR response at this time-point. This result questions the previously forwarded notion that the psychological "moment of insight" that signals the start of the humor response is always associated with heightened cardiovascular activity. This discrepancy is discussed in relation to possible differences in the cognitive processes required to comprehend different forms of humor. At a broader level, our results also demonstrate the advantages of combining different psychophysiological measures to examine psychological phenomena, and illustrate how one such measure can constrain the interpretation of others.

  16. Using Photo-Elicitation with Native American Students to Explore Perceptions of the Physical Library

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    Karen Neurohr

    2016-04-01

    Full Text Available Abstract Objective – This research project explored Native American students’ perceptions of the Edmon Low Library at Oklahoma State University (OSU. The study sought to understand how Native American students perceived the role of the academic library in their lives, and which elements of the library students depicted and described as holding meaning for them. Methods – Photo-elicitation, a form of visual research and a participatory research method, was the primary method chosen to explore students’ perceptions of the library. To qualify for this study, students self-identified as Native American and as frequent library users. They also had completed three or more semesters of study at OSU. Five students followed a photo prompt for taking at least fifteen pictures of the library, then participated in two separate interviews with the primary researcher. Participants also completed a demographic/questionnaire form, answered semi-structured questions, and ranked the photos they took. Results – This study produced several emergent findings. First, students expressed uncertainty about the library’s books. Second, functional library tools such as express printers and library signage played a valuable role for facilitating student work. Third, the method of photo-elicitation was enjoyable for students and served as library discovery. Fourth, Native American resources and exhibits in the library had varied salience for students. Conclusion – Limited research focuses on Native American students in academic libraries, particularly on how students use and experience the library. Exploring how individual students who identify as Native American perceive the university library enhanced our understanding of how libraries in Predominantly White Institutions (PWIs can best serve and support students. This study provided insight into the method of photo-elicitation interviews. This research also provided practical benefits for student

  17. A critical and interpretive literature review of birthing women's non-elicited pain language.

    Science.gov (United States)

    Power, Stephanie; Bogossian, Fiona E; Sussex, Roland; Strong, Jenny

    2017-10-01

    Standardised pain assessment i.e. the McGill Pain Questionnaire provide an elicited pain language. Midwives observe spontaneous non-elicited pain language to guide their assessment of how a woman is coping with labour. This paper examined the labour pain experience using the questions: What type of pain language do women use? Do any of the words match the descriptors of standardised pain assessments? What type of information doverbal and non-verbal cues provide to the midwife? A literature search was conducted in 2013. Studies were included if they had pain as the primary outcome and examined non-elicited pain language from the maternal perspective. A total of 12 articles were included. The analysis revealed six categories in which labour pain can be viewed: 'positive', 'negative', 'physical', 'emotional', 'transcendent' and 'natural'. Women's language comprised i.e. prefixes and suffixes, which indicate the qualities of pain, and figurative language. Language indicated location of pain, gave insight into other life phenomena i.e. death, and shared similarities with standardised pain assessmentdescriptors. Labour cues were 'functional', 'dysfunctional,' or 'neutral' (part of the physiological childbirth process), and were verbal, non-verbal, emotional, psychological, physical behaviour or reactions, or tactile. Labour can bring about a spectrum of sensations and therefore emotions from happiness and pleasure to suffering and grief. Spontaneous pain language comprises verbal language and non-verbal behaviour. Narratives are an effective form of pain communication in that they provide details regarding the quality, nature and dimensions of pain, and details notcaptured in quantitative data. Copyright © 2017 Australian College of Midwives. Published by Elsevier Ltd. All rights reserved.

  18. Event-related potentials elicited by pre-attentive emotional changes in temporal context.

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    Tomomi Fujimura

    Full Text Available The ability to detect emotional change in the environment is essential for adaptive behavior. The current study investigated whether event-related potentials (ERPs can reflect emotional change in a visual sequence. To assess pre-attentive processing, we examined visual mismatch negativity (vMMN: the negative potentials elicited by a deviant (infrequent stimulus embedded in a sequence of standard (frequent stimuli. Participants in two experiments pre-attentively viewed visual sequences of Japanese kanji with different emotional connotations while ERPs were recorded. The visual sequence in Experiment 1 consisted of neutral standards and two types of emotional deviants with a strong and weak intensity. Although the results indicated that strongly emotional deviants elicited more occipital negativity than neutral standards, it was unclear whether these negativities were derived from emotional deviation in the sequence or from the emotional significance of the deviants themselves. In Experiment 2, the two identical emotional deviants were presented against different emotional standards. One type of deviants was emotionally incongruent with the standard and the other type of deviants was emotionally congruent with the standard. The results indicated that occipital negativities elicited by deviants resulted from perceptual changes in a visual sequence at a latency of 100-200 ms and from emotional changes at latencies of 200-260 ms. Contrary to the results of the ERP experiment, reaction times to deviants showed no effect of emotional context; negative stimuli were consistently detected more rapidly than were positive stimuli. Taken together, the results suggest that brain signals can reflect emotional change in a temporal context.

  19. Brief environmental enrichment elicits metaplasticity of hippocampal synaptic potentiation in vivo

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    Denise eManahan-Vaughan

    2012-12-01

    Full Text Available Long-term environmental enrichment (EE elicits enduring effects on the adult brain, including altered synaptic plasticity. Synaptic plasticity may underlie memory formation and includes robust (>24h and weak (<2h forms of long-term potentiation (LTP and long-term depression (LTD. Most studies of the effect of EE on synaptic efficacy have examined the consequences of very prolonged EE-exposure. It is unclear whether brief exposure to EE can alter synaptic plasticity. Clarifying this issue could help develop strategies to address cognitive deficits arising from neglect in children or adults.We assessed whether short-term EE elicits alterations in hippocampal synaptic plasticity and if social context may play a role. Adult mice were exposed to EE for 14 consecutive days. We found that robust late-LTP (>24h and short-term depression (<2h at Schaffer-collateral-CA1 synapses in freely behaving mice were unaltered, whereas early-LTP (E-LTP, <2h was significantly enhanced by EE. Effects were transient: E-LTP returned to control levels 1 week after cessation of EE. Six weeks later animals were re-exposed to EE for 14d. Under these conditions, E-LTP was facilitated into L-LTP (>24h, suggesting that metaplasticity was induced during the first EE experience and that EE-mediated modifications are cumulative. Effects were absent in mice that underwent solitary enrichment or were group-housed without EE. These data suggest that EE in naïve animals strengthens E-LTP, and also promotes L-LTP in animals that underwent EE in the past. This indicates that brief exposure to EE, particularly under social conditions can elicit lasting positive effects on synaptic strength that may have beneficial consequences for cognition that depends on synaptic plasticity.

  20. Proteins differentially expressed in elicited cell suspension culture of Podophyllum hexandrum with enhanced podophyllotoxin content

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    Bhattacharyya Dipto

    2012-05-01

    Full Text Available Abstract Background Podophyllotoxin (PTOX, the precursor for semi-synthesis of cancer therapeutics like etoposide, teniposide and etophos, is primarily obtained from an endangered medicinal herb, Podophyllum hexandrum Royle. PTOX, a lignan is biosynthetically derived from the phenylpropanoid pathway. The aim of this study is to investigate changes in the P. hexandrum cell proteome potentially related to PTOX accumulation in response to methyl jasmonate (MeJA elicitation. High-resolution two-dimensional gel electrophoresis (2-DE followed by colloidal Coomassie staining and mass spectrometric analysis was used to detect statistically significant changes in cell’s proteome. Result The HPLC analysis showed approximately 7–8 fold change in accumulation of PTOX, in the 12day old cell suspension culture (i.e. after 9days of elicitation elicited with 100 μM MeJA as compared to the control. Using 2-DE a total of 233 spots was detected, out of which 105 spots were identified by MALDI TOF-TOF MS/MS. Data were subjected to functional annotation from a biological point of view through KEGG. The phenylpropanoid and monolignol pathway enzymes were identified, amongst these, chalcone synthase, polyphenol oxidase, caffeoyl CoA 3-O-methyltransferase, S-adenosyl-L-methionine-dependent methyltransferases, caffeic acid-O-methyl transferase etc. are noted as important. The relation of other differentially accumulated proteins with varied effects caused by elicitors on P. hexandrum cells namely stress and defense related protein, transcription and DNA replication and signaling are also discussed. Conclusions Elicitor-induced PTOX accumulation in P. hexandrum cell cultures provides a responsive model system to profile modulations in proteins related to phenylpropanoid/monolignol biosynthesis and other defense responses. Present findings form a baseline for future investigation on a non-sequenced medicinal herb P. hexandrum at molecular level.