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

International Nuclear Information System (INIS)

Schillaci, Roxana; Charreau, Eduardo H; Maronna, Esteban; Roa, Juan C; Elizalde, Patricia V; Guzmán, Pablo; Cayrol, Florencia; Beguelin, Wendy; Díaz Flaqué, María C; Proietti, Cecilia J; Pineda, Viviana; Palazzi, Jorge; Frahm, Isabel

2012-01-01

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

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

Directory of Open Access Journals (Sweden)

Schillaci Roxana

2012-02-01

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

ACETYL-L-CARNITINE AFFECTS THE ELECTRICAL ACTIVITY OF MECHANOSENSORY NEURONS IN HIRUDO MEDICINALIS GANGLIA

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Giovanna Traina

2017-04-01

Full Text Available Was previously discovered that in the leech Hirudo medicinalis, acetyl-l-carnitine (ALC affects forms of non-associative learning, such as sensitization and dishabituation, due to nociceptive stimulation of the dorsal skin in the swim induction behavioural paradigm, likely through modulating the activity of the mechanosensory tactile (T neurons, which initiate swimming. Since was found that ALC impaired sensitization and dishabituation, both of which are mediated by the neurotransmitter serotonin, the present study analyzed how ALC may interfere with the sensitizing response. Was already found that ALC reduced the activity of nociceptive (N neurons, which modulate T cell activity through serotonergic mediation.

Infección nasal por Hirudo medicinalis y breve revisión del tema

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María Beltran

1997-07-01

Full Text Available Se presentan dos casos de infección nasal por Hirudo medicinalis "sanguijuela medicinal". Estos gusanos se obtuvieron de las fosas nasales de dos niños, uno de ellos, del caserio Zapatero, Coñumbuqui, Lamas (San Martín, Perú y el otro de San Francisco (Ayacucho, Perú, de 6 y 1,5 años de edad, respectivamente. El tamaño de las sanguijuelas fue de 2.5 y 6 cm. en cada uno de los casos. Las sanguijuelas tienen importancia en la salud pública por que pueden producir anemia grave, asfixia y la muerte.

1999-2003 Shortwave Characterizations of Earth Radiation Budget Satellite (ERBS)/Earth Radiation Budget Experiment (ERBE) Broadband Active Cavity Radiometer Sensors

Science.gov (United States)

Lee, Robert B., III; Smith, George L.; Wong, Takmeng

2008-01-01

From October 1984 through May 2005, the NASA Earth Radiation Budget Satellite (ERBS/ )/Earth Radiation Budget Experiment (ERBE)ERBE nonscanning active cavity radiometers (ACR) were used to monitor long-term changes in the earth radiation budget components of the incoming total solar irradiance (TSI), earth-reflected TSI, and earth-emitted outgoing longwave radiation (OLR). From September1984 through September 1999, using on-board calibration systems, the ERBS/ERBE ACR sensor response changes, in gains and offsets, were determined from on-orbit calibration sources and from direct observations of the incoming TSI through calibration solar ports at measurement precision levels approaching 0.5 W/sq m , at satellite altitudes. On October 6, 1999, the onboard radiometer calibration system elevation drive failed. Thereafter, special spacecraft maneuvers were performed to observe cold space and the sun in order to define the post-September 1999 geometry of the radiometer measurements, and to determine the October 1999-September 2003 ERBS sensor response changes. Analyses of these special solar and cold space observations indicate that the radiometers were pointing approximately 16 degrees away from the spacecraft nadir and on the anti-solar side of the spacecraft. The special observations indicated that the radiometers responses were stable at precision levels approaching 0.5 W/sq m . In this paper, the measurement geometry determinations and the determinations of the radiometers gain and offset are presented, which will permit the accurate processing of the October 1999 through September 2003 ERBE data products at satellite and top-of-the-atmosphere altitudes.

A peptide antagonist of ErbB receptors, Inherbin3, induces neurite outgrowth from rat cerebellar granule neurons through ErbB1 inhibition

DEFF Research Database (Denmark)

Xu, Ruodan; Pankratova, Stanislava; Christiansen, Søren Hofman

2013-01-01

ErbB receptors not only function in cancer, but are also key developmental regulators in the nervous system. We previously identified an ErbB1 peptide antagonist, Inherbin3, that is capable of inhibiting tumor growth in vitro and in vivo. In this study, we found that inhibition of ErbB1 kinase ac...

ErbB2 resembles an autoinhibited invertebrate epidermal growth factor receptor

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

2009-09-25

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

Transcriptional profiling of ErbB signalling in mammary luminal epithelial cells - interplay of ErbB and IGF1 signalling through IGFBP3 regulation

International Nuclear Information System (INIS)

Worthington, Jenny; Bertani, Mariana; Chan, Hong-Lin; Gerrits, Bertran; Timms, John F

2010-01-01

Members of the ErbB family of growth factor receptors are intricately linked with epithelial cell biology, development and tumourigenesis; however, the mechanisms involved in their downstream signalling are poorly understood. Indeed, it is unclear how signal specificity is achieved and the relative contribution each receptor has to specific gene expression. Gene expression profiling of a human mammary luminal epithelial cell model of ErbB2-overexpression was carried out using cDNA microarrays with a common RNA reference approach to examine long-term overlapping and differential responses to EGF and heregulin beta1 treatment in the context of ErbB2 overexpression. Altered gene expression was validated using quantitative real time PCR and/or immunoblotting. One gene of interest was targeted for further characterisation, where the effects of siRNA-mediated silencing on IGF1-dependent signalling and cellular phenotype were examined and compared to the effects of loss of ErbB2 expression. 775 genes were differentially expressed and clustered in terms of their growth factor responsiveness. As well as identifying uncharacterized genes as novel targets of ErbB2-dependent signalling, ErbB2 overexpression augmented the induction of multiple genes involved in proliferation (e.g. MYC, MAP2K1, MAP2K3), autocrine growth factor signalling (VEGF, PDGF) and adhesion/cytoskeletal regulation (ZYX, THBS1, VCL, CNN3, ITGA2, ITGA3, NEDD9, TAGLN), linking them to the hyper-poliferative and altered adhesive phenotype of the ErbB2-overexpressing cells. We also report ErbB2-dependent down-regulation of multiple interferon-stimulated genes that may permit ErbB2-overexpressing cells to resist the anti-proliferative action of interferons. Finally, IGFBP3 was unique in its pattern of regulation and we further investigated a possible role for IGFBP3 down-regulation in ErbB2-dependent transformation through suppressed IGF1 signalling. We show that IGF1-dependent signalling and proliferation were

ErbB polymorphisms: Insights and implications for response to targeted cancer therapeutics

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Moulay A Alaoui-Jamali

2015-02-01

Full Text Available Advances in high-throughput genomic-scanning have expanded the repertory of genetic variations in DNA sequences encoding ErbB tyrosine kinase receptors in humans, including single nucleotide polymorphisms (SNPs, polymorphic repetitive elements, microsatellite variations, small-scale insertions and deletions. The ErbB family members: EGFR, ErbB2, ErbB3 and ErbB4 receptors are established as drivers of many aspects of tumor initiation and progression to metastasis. This knowledge has provided rationales for the development of an arsenal of anti-ErbB therapeutics, ranging from small molecule kinase inhibitors to monoclonal antibodies. Anti-ErbB agents are becoming the cornerstone therapeutics for the management of cancers that overexpress hyperactive variants of ErbB receptors, in particular ErbB2-positive breast cancer and non-small cell lung carcinomas. However, their clinical benefit has been limited to a subset of patients due to a wide heterogeneity in drug response despite the expression of the ErbB targets, attributed to intrinsic (primary and to acquired (secondary resistance. Somatic mutations in ErbB tyrosine kinase domains have been extensively investigated in preclinical and clinical setting as determinants for either high sensitivity or resistance to anti-ErbB therapeutics. In contrast, only scant information is available on the impact of SNPs, which are widespread in genes encoding ErbB receptors, on receptor structure and activity, and their predictive values for drug susceptibility. This review aims to briefly update polymorphic variations in genes encoding ErbB receptors based on recent advances in deep sequencing technologies, and to address challenging issues for a better understanding of the functional impact of single versus combined SNPs in ErbB genes to receptor topology, receptor-drug interaction, and drug susceptibility. The potential of exploiting SNPs in the era of stratified targeted therapeutics is discussed.

A combination of Trastuzumab and 17-AAG induces enhanced ubiquitinylation and lysosomal pathway-dependent ErbB2 degradation and cytotoxicity in ErbB2-overexpressing breast cancer cells.

Science.gov (United States)

Raja, Srikumar M; Clubb, Robert J; Bhattacharyya, Mitra; Dimri, Manjari; Cheng, Hao; Pan, Wei; Ortega-Cava, Cesar; Lakku-Reddi, Alagarsamy; Naramura, Mayumi; Band, Vimla; Band, Hamid

2008-10-01

ErbB2 (or Her2/Neu) overexpression in breast cancer signifies poorer prognosis, yet it has provided an avenue for targeted therapy as demonstrated by the success of the humanized monoclonal antibody Trastuzumab (Herceptin). Resistance to Trastuzumab and eventual failure in most cases, however, necessitate alternate ErbB2-targeted therapies. HSP90 inhibitors such as 17-allylaminodemethoxygeldanamycin (17-AAG), potently downregulate the cell surface ErbB2. While the precise mechanisms of Trastuzumab or 17-AAG action remain unclear, ubiquitinylation-dependent proteasomal or lysosomal degradation of ErbB2 appears to play a substantial role. As Trastuzumab and 17-AAG induce the recruitment of distinct E3 ubiquitin ligases, Cbl and CHIP respectively, to ErbB2, we hypothesized that 17-AAG and Trastuzumab combination could induce a higher level of ubiquitinylation and downregulation of ErbB2 as compared to single drug treatments. We present biochemical and cell biological evidence that combined 17-AAG and Trastuzumab treatment of ErbB2-overexpressing breast cancer cell lines leads to enhanced ubiquitinylation, downregulation from the cell surface and lysosomal degradation of ErbB2. Importantly, combined 17-AAG and Trastuzumab treatment induced synergistic growth arrest and cell death specifically in ErbB2-overexpressing but not in ErbB2-low breast cancer cells. Our results suggest the 17-AAG and Trastuzumab combination as a mechanism-based combinatorial targeted therapy for ErbB2-overexpressing breast cancer patients.

Role of ErbB receptors in cancer cell migration and invasion

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Aline eAppert-Collin

2015-11-01

Full Text Available Growth factors mediate their diverse biologic responses (regulation of cellular proliferation, differentiation, migration and survival by binding to and activating cell-surface receptors with intrinsic protein kinase activity named Receptor Tyrosine Kinases (RTKs. About 60 RTKs have been identified and can be classified into more than 16 different receptor families. Their activity is normally tightly controlled and regulated. Overexpression of RTK proteins or functional alterations caused by mutations in the corresponding genes or abnormal stimulation by autocrine growth factor loops contribute to constitutive RTK signaling, resulting in alterations in the physiological activities of cells. The ErbB receptor family of RTKs comprises four distinct receptors: the EGFR (also known as ErbB1/HER1, ErbB2 (neu, HER2, ErbB3 (HER3 and ErbB4 (HER4. ErbB family members are often overexpressed, amplified, or mutated in many forms of cancer, making them important therapeutic targets. EGFR has been found to be amplified in gliomas and non-small-cell lung carcinoma while ErbB2 amplifications are seen in breast, ovarian, bladder, non-small-cell lung carcinoma, as well as several other tumor types. Several data have shown that ErbB receptor family and its downstream pathway regulate epithelial-mesenchymal transition, migration, and tumor invasion by modulating extracellular matrix components. Recent findings indicate that extracellular matrix components such as matrikines bind specifically to EGF receptor and promote cell invasion. In this review, we will present an in-depth overview of the structure, mechanisms, cell signaling, and functions of ErbB family receptors in cell adhesion and migration. Furthermore, we will describe in a last part the new strategies developed in anti-cancer therapy to inhibit ErbB family receptor activation.

Preubiquitinated chimeric ErbB2 is constitutively endocytosed and subsequently degraded in lysosomes

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

2013-02-01

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

Preubiquitinated chimeric ErbB2 is constitutively endocytosed and subsequently degraded in lysosomes

International Nuclear Information System (INIS)

Vuong, Tram Thu; Berger, Christian; Bertelsen, Vibeke; Rødland, Marianne Skeie; Stang, Espen; Madshus, Inger Helene

2013-01-01

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

Interaction with epsin 1 regulates the constitutive clathrin-dependent internalization of ErbB3.

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Szymanska, Monika; Fosdahl, Anne Marthe; Raiborg, Camilla; Dietrich, Markus; Liestøl, Knut; Stang, Espen; Bertelsen, Vibeke

2016-06-01

In contrast to other members of the EGF receptor family, ErbB3 is constitutively internalized in a clathrin-dependent manner. Previous studies have shown that ErbB3 does not interact with the coated pit localized adaptor complex 2 (AP-2), and that ErbB3 lacks two AP-2 interacting internalization signals identified in the EGF receptor. Several other clathrin-associated sorting proteins which may recruit cargo into coated pits have, however, been identified, and the study was performed to identify adaptors needed for constitutive internalization of ErbB3. A high-throughput siRNA screen was used to identify adaptor proteins needed for internalization of ErbB3. Upon knock-down of candidate proteins internalization of ErbB3 was identified using an antibody-based internalization assay combined with automatic fluorescence microscopy. Among 29 candidates only knock-down of epsin 1 turned out to inhibit ErbB3. Epsin 1 has ubiquitin interacting motifs (UIMs) and we show that ErbB3 interacts with an epsin 1 deletion mutant containing these UIMs. In support of an ErbB3-epsin 1 UIM dependent interaction, we show that ErbB3 is constitutively ubiquitinated, but that both ubiquitination and the ErbB3-epsin 1 interaction increase upon ligand binding. Altogether the results are consistent with a model whereby both constitutive and ligand-induced internalization of ErbB3 are regulated through interaction with epsin 1. Internalization is an important regulator of growth factor receptor mediated signaling and the current study identify mechanisms regulating plasma membrane turnover of ErbB3. Copyright © 2016 Elsevier B.V. All rights reserved.

Large-scale analysis by SAGE reveals new mechanisms of v-erbA oncogene action

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Faure Claudine

2007-10-01

Full Text Available Abstract Background: The v-erbA oncogene, carried by the Avian Erythroblastosis Virus, derives from the c-erbAα proto-oncogene that encodes the nuclear receptor for triiodothyronine (T3R. v-ErbA transforms erythroid progenitors in vitro by blocking their differentiation, supposedly by interference with T3R and RAR (Retinoic Acid Receptor. However, v-ErbA target genes involved in its transforming activity still remain to be identified. Results: By using Serial Analysis of Gene Expression (SAGE, we identified 110 genes deregulated by v-ErbA and potentially implicated in the transformation process. Bioinformatic analysis of promoter sequence and transcriptional assays point out a potential role of c-Myb in the v-ErbA effect. Furthermore, grouping of newly identified target genes by function revealed both expected (chromatin/transcription and unexpected (protein metabolism functions potentially deregulated by v-ErbA. We then focused our study on 15 of the new v-ErbA target genes and demonstrated by real time PCR that in majority their expression was activated neither by T3, nor RA, nor during differentiation. This was unexpected based upon the previously known role of v-ErbA. Conclusion: This paper suggests the involvement of a wealth of new unanticipated mechanisms of v-ErbA action.

Pharmacological Targeting the REV-ERBs in Sleep/Wake Regulation

Science.gov (United States)

Amador, Ariadna; Huitron-Resendiz, Salvador; Roberts, Amanda J.; Kamenecka, Theodore M.; Solt, Laura A.; Burris, Thomas P.

2016-01-01

The circadian clock maintains appropriate timing for a wide range of behaviors and physiological processes. Circadian behaviors such as sleep and wakefulness are intrinsically dependent on the precise oscillation of the endogenous molecular machinery that regulates the circadian clock. The identical core clock machinery regulates myriad endocrine and metabolic functions providing a link between sleep and metabolic health. The REV-ERBs (REV-ERBα and REV-ERBβ) are nuclear receptors that are key regulators of the molecular clock and have been successfully targeted using small molecule ligands. Recent studies in mice suggest that REV-ERB-specific synthetic agonists modulate metabolic activity as well as alter sleep architecture, inducing wakefulness during the light period. Therefore, these small molecules represent unique tools to extensively study REV-ERB regulation of sleep and wakefulness. In these studies, our aim was to further investigate the therapeutic potential of targeting the REV-ERBs for regulation of sleep by characterizing efficacy, and optimal dosing time of the REV-ERB agonist SR9009 using electroencephalographic (EEG) recordings. Applying different experimental paradigms in mice, our studies establish that SR9009 does not lose efficacy when administered more than once a day, nor does tolerance develop when administered once a day over a three-day dosing regimen. Moreover, through use of a time response paradigm, we determined that although there is an optimal time for administration of SR9009 in terms of maximal efficacy, there is a 12-hour window in which SR9009 elicited a response. Our studies indicate that the REV-ERBs are potential therapeutic targets for treating sleep problems as those encountered as a consequence of shift work or jet lag. PMID:27603791

Digitalisierung des Kulturellen Erbes (Europas)

NARCIS (Netherlands)

Gruber, Marion

2011-01-01

Gruber, M. R. (2011, 13 December). Digitalisierung des Kulturellen Erbes (Europas). Guest lecture at the IPMZ - Institute of Mass Communication and Media Research, Devision Media Change & Innovation, University of Zurich, Switzerland.

Rev-erb beta regulates the Srebp-1c promoter and mRNA expression in skeletal muscle cells

Energy Technology Data Exchange (ETDEWEB)

Ramakrishnan, Sathiya N.; Lau, Patrick; Crowther, Lisa M. [The University of Queensland, Institute for Molecular Bioscience, St. Lucia, Qld 4072 (Australia); Cleasby, Mark E. [Diabetes and Obesity Research Program, Garvan Institute of Medical Research, St. Vincent' s Hospital, 384 Victoria Street, Darlinghurst, Sydney, NSW 2010 (Australia); Millard, Susan; Leong, Gary M. [The University of Queensland, Institute for Molecular Bioscience, St. Lucia, Qld 4072 (Australia); Cooney, Gregory J. [Diabetes and Obesity Research Program, Garvan Institute of Medical Research, St. Vincent' s Hospital, 384 Victoria Street, Darlinghurst, Sydney, NSW 2010 (Australia); Muscat, George E.O., E-mail: g.muscat@imb.uq.edu.au [The University of Queensland, Institute for Molecular Bioscience, St. Lucia, Qld 4072 (Australia)

2009-10-30

The nuclear hormone receptor, Rev-erb beta operates as a transcriptional silencer. We previously demonstrated that exogenous expression of Rev-erb{beta}{Delta}E in skeletal muscle cells increased Srebp-1c mRNA expression. We validated these in vitro observations by injection of an expression vector driving Rev-erb{beta}{Delta}E expression into mouse tibialis muscle that resulted in increased Srebp-1c mRNA expression. Paradoxically, Rev-erb{beta} siRNA expression in skeletal muscle cells repressed Srebp-1c expression, and indicated that Rev-erb{beta} expression was necessary for Srebp-1c expression. ChIP analysis demonstrated that Rev-erb{beta} was recruited to the Srebp-1c promoter. Moreover, Rev-erb{beta} trans-activated the Srebp-1c promoter, in contrast, Rev-erb{beta} efficiently repressed the Rev-erb{alpha} promoter, a previously characterized target gene. Finally, treatment with the Rev-erb agonist (hemin) (i) increased the trans-activation of the Srebp-1c promoter by Rev-erb{beta}; and (ii) increased Rev-erb{beta} and Srebp-1c mRNA expression. These data suggest that Rev-erb{beta} has the potential to activate gene expression, and is a positive regulator of Srebp-1c, a regulator of lipogenesis.

Kinesio arm taping as prophylaxis against the development of Erb's Engram.

Science.gov (United States)

ElKhatib, Radwa S; ElNegmy, Emam H; Salem, Amina H; Sherief, AbdelAziz A

2013-11-01

An Erb's Engram is a common debility that develops in recovering children with Erb's palsy. The purpose of this study was to investigate the effect of kinesiotaping over the deltoid and the forearm on the development of proper upper extremity function in children recovering from Erb's palsy. Thirty patients with Erb's palsy participated for 3 months in this study and were equally divided into two groups; control group A and study group B. The two groups received the same designed physical therapy program, while group B along the program, received kinesiotaping over the deltoid and the forearm. The subjects were evaluated, pre and post-treatment, and scored functionally, using the Toronto Active Motion Scale, and objectively, using an EMG device utilized to obtain the percentages of degeneration of the deltoid and the biceps muscles. Post-treatment values of six out of nine measured variables, between the two groups, revealed significant difference in favor of group B. The obtained results strongly support the introduction of kinesiotaping of the deltoid and the forearm as an adjunct to the treatment program of Erb's palsied children.

ErbB2 regulates NHEJ repair pathway by affecting erbB1-triggered IR-induced Akt activity

International Nuclear Information System (INIS)

Toulany, Mahmoud; Peter Rodemann, H.

2009-01-01

We have already reported that erbBl-PI3K-AKT signaling is an important pathway in regulating radiation sensitivity and DNA double strand break repair of human tumor cells. In the present study using small interfering RNA and pharmacological inhibitors in non-small cell lung cancer cell lines we investigated the role of Aktl on radiation-induced DNA-PKcs activity and DNA-double strand break (DNA-DSB) repair. Likewise, the function of erbB2 as hetrodimerization partner of erbBl in radiation-induced Akt activity and regulation of DNA-dsb repair through DNA-PKcs was evaluated. In A549 and H460 transfected with AKTl-siRNA radiation-induced phosphorylation of DNA-PKcs the key enzyme regulating NHEJ repair pathway was markedly inhibited. In both cell lines downregulation of Aktl led to a significant enhancement of residual DNA-DSB, i.e. impaired DNA-DSB repair. Interestingly, in cells transfected with DNA-PKcs-siRNA a lack of effect of AKTl-siRNA on enhancement of residual DNA-DSBs was observed. This results indicate that Aktl regulates NHEJ repair in a DNA-PKcs dependent manner

[Bacterial synthesis, purification, and solubilization of transmembrane segments of ErbB family members].

Science.gov (United States)

Goncharuk, M V; Shul'ga, A A; Ermoliuk, Ia S; Tkach, E N; Goncharuk, S A; Pustovalova, Iu E; Mineev, K S; Bocharov, É V; Maslennikov, I V; Arsen'ev, A S; Kirpichnikov, M P

2011-01-01

A family of epidermal growth factor receptors, ErbB, represents an important class of receptor tyrosine kinases, playing a leading role in cellular growth, development and differentiation. Transmembrane domains of these receptors transduce biochemical signals across plasma membrane via lateral homo- and heterodimerization. Relatively small size of complexes of ErbB transmembrane domains with detergents or lipids allows one to study their detailed spatial structure using three-dimensional heteronuclear high-resolution NMR spectroscopy. Here, we describe the effective expression system and purification procedure for preparative-scale production of transmembrane peptides from four representatives of ErbB family, ErbB1, ErbB2, ErbB3, ErbB4, for structural studies. The recombinant peptides were produced in Escherichia coli BL21(DE3)pLysS as C-terminal extensions of thioredoxin A. The fusion protein cleavage was accomplished with the light subunit of human enterokinase. Several (10-30) milligrams of purified isotope-labeled transmembrane peptides were isolated with the use of a simple and convenient procedure, which consists of consecutive steps of immobilized metal affinity chromatography and cation-exchange chromatography. The purified peptides were reconstituted in lipid/detergent environment (micelles or bicelles) and characterized using dynamic light scattering, CD and NMR spectroscopy. The data obtained indicate that the purified ErbB transmembrane peptides are suitable for structural and dynamic studies of their homo- and heterodimer complexes using high resolution NMR spectroscopy.

ErbB4 localization to cardiac myocyte nuclei, and its role in myocyte DNA damage response

International Nuclear Information System (INIS)

Icli, Basak; Bharti, Ajit; Pentassuglia, Laura; Peng, Xuyang; Sawyer, Douglas B.

2012-01-01

Highlights: ► ErbB4 localizes to cardiac myocyte nuclei as a full-length receptor. ► Cardiac myocytes express predominantly JM-a/CYT-1 ErbB4. ► Myocyte p53 activation in response to doxorubicin requires ErbB4 activity. -- Abstract: The intracellular domain of ErbB4 receptor tyrosine kinase is known to translocate to the nucleus of cells where it can regulate p53 transcriptional activity. The purpose of this study was to examine whether ErbB4 can localize to the nucleus of adult rat ventricular myocytes (ARVM), and regulate p53 in these cells. We demonstrate that ErbB4 does locate to the nucleus of cardiac myocytes as a full-length protein, although nuclear location occurs as a full-length protein that does not require Protein Kinase C or γ-secretase activity. Consistent with this we found that only the non-cleavable JM-b isoform of ErbB4 is expressed in ARVM. Doxorubicin was used to examine ErbB4 role in regulation of a DNA damage response in ARVM. Doxorubicin induced p53 and p21 was suppressed by treatment with AG1478, an EGFR and ErbB4 kinase inhibitor, or suppression of ErbB4 expression with small interfering RNA. Thus ErbB4 localizes to the nucleus as a full-length protein, and plays a role in the DNA damage response induced by doxorubicin in cardiac myocytes.

The neuregulin receptor ErbB-4 interacts with PDZ-containing proteins at neuronal synapses

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Garcia, Rolando A. G.; Vasudevan, Kuzhalini; Buonanno, Andres

2000-01-01

Neuregulins regulate the expression of ligand- and voltage-gated channels in neurons and skeletal muscle by the activation of their cognate tyrosine kinase receptors, ErbB 1–4. The subcellular distribution and mechanisms that regulate the localization of ErbB receptors are unknown. We have found that ErbB receptors are present in brain subcellular fractions enriched for postsynaptic densities (PSD). The ErbB-4 receptor is unique among the ErbB proteins because its C-terminal tail (T-V-V) conforms to a sequence that binds to a protein motif known as the PDZ domain. Using the yeast two-hybrid system, we found that the C-terminal region of ErbB-4 interacts with the three related membrane-associated guanylate kinases (MAGUKs) PSD-95/SAP90, PSD-93/chapsyn-110, and SAP 102, which harbor three PDZ domains, as well as with β2-syntrophin, which has a single PDZ domain. As with N-methyl-d-aspartate (NMDA) receptors, ErbB4 interacts with the first two PDZ domains of PSD-95. Using coimmunoprecipitation assays, we confirmed the direct interactions between ErbB-4 and PSD-95 in transfected heterologous cells, as well as in vivo, where both proteins are coimmunoprecipitated from brain lysates. Moreover, evidence for colocalization of these proteins was also observed by immunofluorescence in cultured hippocampal neurons. ErbB-4 colocalizes with PSD-95 and NMDA receptors at a subset of excitatory synapses apposed to synaptophysin-positive presynaptic terminals. The capacity of ErbB receptors to interact with PDZ-domain proteins at cell junctions is conserved from invertebrates to mammals. As discussed, the interactions found between receptor tyrosine kinases and MAGUKs at neuronal synapses may have important implications for activity-dependent plasticity. PMID:10725395

Modulation of the Neuregulin 1/ErbB system after skeletal muscle denervation and reinnervation.

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Morano, Michela; Ronchi, Giulia; Nicolò, Valentina; Fornasari, Benedetta Elena; Crosio, Alessandro; Perroteau, Isabelle; Geuna, Stefano; Gambarotta, Giovanna; Raimondo, Stefania

2018-03-22

Neuregulin 1 (NRG1) is a growth factor produced by both peripheral nerves and skeletal muscle. In muscle, it regulates neuromuscular junction gene expression, acetylcholine receptor number, muscle homeostasis and satellite cell survival. NRG1 signalling is mediated by the tyrosine kinase receptors ErbB3 and ErbB4 and their co-receptors ErbB1 and ErbB2. The NRG1/ErbB system is well studied in nerve tissue after injury, but little is known about this system in skeletal muscle after denervation/reinnervation processes. Here, we performed a detailed time-course expression analysis of several NRG1 isoforms and ErbB receptors in the rat superficial digitorum flexor muscle after three types of median nerve injuries of different severities. We found that ErbB receptor expression was correlated with the innervated state of the muscle, with upregulation of ErbB2 clearly associated with the denervation state. Interestingly, the NRG1 isoforms were differently regulated depending on the nerve injury type, leading to the hypothesis that both the NRG1α and NRG1β isoforms play a key role in the muscle reaction to injury. Indeed, in vitro experiments with C2C12 atrophic myotubes revealed that both NRG1α and NRG1β treatment influences the best-known atrophic pathways, suggesting that NRG1 might play an anti-atrophic role.

Endothelial ErbB4 deficit induces alterations in exploratory behavior and brain energy metabolism in mice.

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Wu, Gang; Liu, Xiu-Xiu; Lu, Nan-Nan; Liu, Qi-Bing; Tian, Yun; Ye, Wei-Feng; Jiang, Guo-Jun; Tao, Rong-Rong; Han, Feng; Lu, Ying-Mei

2017-06-01

The receptor tyrosine kinase ErbB4 is present throughout the primate brain and has a distinct functional profile. In this study, we investigate the potential role of endothelial ErbB4 receptor signaling in the brain. Here, we show that the endothelial cell-specific deletion of ErbB4 induces decreased exploratory behavior in adult mice. However, the water maze task for spatial memory and the memory reconsolidation test reveal no changes; additionally, we observe no impairment in CaMKII phosphorylation in Cdh5Cre;ErbB4 f/f mice, which indicates that the endothelial ErbB4 deficit leads to decreased exploratory activity rather than direct memory deficits. Furthermore, decreased brain metabolism, which was measured using micro-positron emission tomography, is observed in the Cdh5Cre;ErbB4 f/f mice. Consistently, the immunoblot data demonstrate the downregulation of brain Glut1, phospho-ULK1 (Ser555), and TIGAR in the endothelial ErbB4 conditional knockout mice. Collectively, our findings suggest that endothelial ErbB4 plays a critical role in regulating brain function, at least in part, through maintaining normal brain energy homeostasis. Targeting ErbB4 or the modulation of endothelial ErbB4 signaling may represent a rational pharmacological approach to treat neurological disorders. © 2017 John Wiley & Sons Ltd.

Antipsychotic potential of quinazoline ErbB1 inhibitors in a schizophrenia model established with neonatal hippocampal lesioning.

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Mizuno, Makoto; Iwakura, Yuriko; Shibuya, Masako; Zheng, Yingjun; Eda, Takeyoshi; Kato, Taisuke; Takasu, Yohei; Nawa, Hiroyuki

2010-01-01

Hyper-signaling of the epidermal growth factor receptor family (ErbB) is implicated in the pathophysiology of schizophrenia. Various quinazoline inhibitors targeting ErbB1 or ErbB2 - 4 have been developed as anti-cancer agents and might be useful for antipsychotic treatment. In the present study, we used an animal model of schizophrenia established by neonatal hippocampal lesioning and evaluated the neurobehavioral consequences of ErbB1-inhibitor treatment. Subchronic administration of the ErbB1 inhibitor ZD1839 to the cerebroventricle of rats receiving neonatal hippocampal lesioning ameliorated deficits in prepulse inhibition as well as those in the latent inhibition of tone-dependent fear learning. There were no apparent adverse effects on basal learning scores or locomotor activity, however. The administration of other ErbB1 inhibitors, PD153035 and OSI-774, similarly attenuated the prepulse inhibition impairment of this animal model. In parallel, there were decreases in ErbB1 phosphorylation in animals treated with ErbB1 inhibitors. These results indicate an antipsychotic potential of quinazoline ErbB1 inhibitors. ErbB receptor tyrosine kinases may be novel therapeutic targets for schizophrenia or its related psychotic symptoms.

Examining the protective role of ErbB2 modulation in human-induced pluripotent stem cell-derived cardiomyocytes.

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Eldridge, Sandy; Guo, Liang; Mussio, Jodie; Furniss, Mike; Hamre, John; Davis, Myrtle

2014-10-01

Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are being used as an in vitro model system in cardiac biology and in drug discovery (e.g., cardiotoxicity testing). Qualification of these cells for use in mechanistic investigations will require detailed evaluations of cardiomyocyte signaling pathways and cellular responses. ErbB signaling and the ligand neuregulin play critical roles in survival and functional integrity of cardiac myocytes. As such, we sought to characterize the expression and activity of the ErbB family of receptors. Antibody microarray analysis performed on cell lysates derived from maturing hiPSC-CMs detected expression of ∼570 signaling proteins. EGFR/ErbB1, HER2/ErbB2, and ErbB4, but not ErbB3 receptors, of the epidermal growth factor receptor family were confirmed by Western blot. Activation of ErbB signaling by neuregulin-1β (NRG, a natural ligand for ErbB4) and its modulation by trastuzumab (a monoclonal anti-ErbB2 antibody) and lapatinib (a small molecule ErbB2 tyrosine kinase inhibitor) were evaluated through assessing phosphorylation of AKT and Erk1/2, two major downstream kinases of ErbB signaling, using nanofluidic proteomic immunoassay. Downregulation of ErbB2 expression by siRNA silencing attenuated NRG-induced AKT and Erk1/2 phosphorylation. Activation of ErbB signaling with NRG, or inhibition with trastuzumab, alleviated or aggravated doxorubicin-induced cardiomyocyte damage, respectively, as assessed by a real-time cellular impedance analysis and ATP measurement. Collectively, these results support the expanded use of hiPSC-CMs to examine mechanisms of cardiotoxicity and support the value of using these cells in early assessments of cardiotoxicity or efficacy. Published by Oxford University Press on behalf of Toxicological Sciences 2014. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Overexpression of c-erbB2 is a negative prognostic factor in anaplastic astrocytomas

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Gulati Michel

2010-03-01

Full Text Available Abstract The epidermal growth factor receptor (EGFR family, consisting of four tyrosine kinase receptors, c-erbB1-4, seems to be influential in gliomagenesis. The aim of this study was to investigate EGFR gene amplification and expression of c-erbB1-4 receptor proteins in human anaplastic astrocytomas. Formalin-fixed and paraffin-embedded sections from 31 cases were investigated by standard immunohistochemical procedures for expression of c-erbB1-4 receptor proteins using commercial antibodies. EGFR gene amplification was studied by fluorescence in situ hybridization using paraffin-embedded tissues. Two monoclonal antibodies, NCL-EGFR-384 and NCL-EGFR, were used for EGFR detection and they displayed positive immunoreactivity in 97% and 71%, respectively. For c-erbB2 detection three monoclonal antibodies, CB11, 3B5, and 5A2, were applied and they displayed positive immunoreactivity in 45%, 100%, and 52%, respectively. Positive immunostaining for c-erbB3 and c-erbB4 was encountered in 97% and 74%, respectively. The EGFR gene was amplified in 9 out of 31 tumors (29%. After adjusting for age, Karnofsky performance status, and extent of surgical resection, Cox multiple regression analysis with overall survival as the dependent variable revealed that c-erbB2 overexpression detected by the monoclonal antibody clone CB11 was a statistically significant poor prognostic factor (P = 0.004. This study shows the convenience and feasibility of immunohistochemistry when determining the expression of receptor proteins in tissue sections of human astrocytomas. The synchronous overexpression of c-erbB1-4 proteins in anaplastic astrocytomas supports their role in the pathogenesis of these tumors. Further, c-erbB2 overexpression seems to predict aggressive behaviour.

ErbB Proteins as Molecular Target of Dietary Phytochemicals in Malignant Diseases

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Alexandru Filippi

2017-01-01

Full Text Available ErbB proteins overexpression, in both normal and mutated forms, is associated with invasive forms of cancer prone to metastasis and with stronger antiapoptotic mechanisms and therefore more challenging to treat. Downstream effectors of ErbB receptors mediating these phenotypic traits include MAPK, STAT, and PI3K/AKT/mTOR pathways. Various phytochemical compounds were studied for their large number of biological effects including anticancer activity. Among these compounds, epigallocatechin-3-gallate (EGCG, the main catechin from green tea leaves, and curcumin, component of the curry powder, constituted the object of numerous studies. Both compounds were shown to act directly either on ErbB expression, or on their downstream signaling molecules. In this paper we aim to review the involvement of ErbB proteins in cancer as well as the biologic activity of EGCG and curcumin in ErbB expressing and overexpressing malignancies. The problems arising in the administration of the two compounds due to their reduced bioavailability when orally administered, as well as the progress made in this field, from using novel formulations to improved dosing regimens or improved synthetic analogs, are also discussed.

ErbB-2 nuclear function in breast cancer growth, metastasis and resistance to therapy.

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Elizalde, Patricia V; Cordo Russo, Rosalía I; Chervo, Maria F; Schillaci, Roxana

2016-12-01

Approximately 15-20% of breast cancers (BC) show either membrane overexpression of ErbB-2 (MErbB-2), a member of the ErbBs family of receptor tyrosine kinases, or ERBB2 gene amplification. Until the development of MErbB-2-targeted therapies, this BC subtype, called ErbB-2-positive, was associated with increased metastatic potential and poor prognosis. Although these therapies have significantly improved overall survival and cure rates, resistance to available drugs is still a major clinical issue. In its classical mechanism, MErbB-2 activates downstream signaling cascades, which transduce its effects in BC. The fact that ErbB-2 is also present in the nucleus of BC cells was discovered over twenty years ago. Also, compelling evidence revealed a non-canonical function of nuclear ErbB-2 as a transcriptional regulator. As a deeper understanding of nuclear ErbB-2 actions would be crucial to the disclosure of its role as a biomarker and a target of therapy in BC, we will here review its function in BC, in particular, its role in growth, metastatic spreading and response to currently available MErbB-2-positive BC therapies. © 2016 Society for Endocrinology.

Cannabinoids reduce ErbB2-driven breast cancer progression through Akt inhibition

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Flores Juana M

2010-07-01

Full Text Available Abstract Background ErbB2-positive breast cancer is characterized by highly aggressive phenotypes and reduced responsiveness to standard therapies. Although specific ErbB2-targeted therapies have been designed, only a small percentage of patients respond to these treatments and most of them eventually relapse. The existence of this population of particularly aggressive and non-responding or relapsing patients urges the search for novel therapies. The purpose of this study was to determine whether cannabinoids might constitute a new therapeutic tool for the treatment of ErbB2-positive breast tumors. We analyzed their antitumor potential in a well established and clinically relevant model of ErbB2-driven metastatic breast cancer: the MMTV-neu mouse. We also analyzed the expression of cannabinoid targets in a series of 87 human breast tumors. Results Our results show that both Δ9-tetrahydrocannabinol, the most abundant and potent cannabinoid in marijuana, and JWH-133, a non-psychotropic CB2 receptor-selective agonist, reduce tumor growth, tumor number, and the amount/severity of lung metastases in MMTV-neu mice. Histological analyses of the tumors revealed that cannabinoids inhibit cancer cell proliferation, induce cancer cell apoptosis, and impair tumor angiogenesis. Cannabinoid antitumoral action relies, at least partially, on the inhibition of the pro-tumorigenic Akt pathway. We also found that 91% of ErbB2-positive tumors express the non-psychotropic cannabinoid receptor CB2. Conclusions Taken together, these results provide a strong preclinical evidence for the use of cannabinoid-based therapies for the management of ErbB2-positive breast cancer.

Dynamic ErbB4 Activity in Hippocampal-Prefrontal Synchrony and Top-Down Attention in Rodents.

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Tan, Zhibing; Robinson, Heath L; Yin, Dong-Min; Liu, Yu; Liu, Fang; Wang, Hongsheng; Lin, Thiri W; Xing, Guanglin; Gan, Lin; Xiong, Wen-Cheng; Mei, Lin

2018-04-18

Top-down attention is crucial for meaningful behaviors and impaired in various mental disorders. However, its underpinning regulatory mechanisms are poorly understood. We demonstrate that the hippocampal-prefrontal synchrony associates with levels of top-down attention. Both attention and synchrony are reduced in mutant mice of ErbB4, a receptor of neuregulin-1. We used chemical genetic and optogenetic approaches to inactivate ErbB4 kinase and ErbB4+ interneurons, respectively, both of which reduce gamma-aminobutyric acid (GABA) activity. Such inhibitions in the hippocampus impair both hippocampal-prefrontal synchrony and top-down attention, whereas those in the prefrontal cortex alter attention, but not synchrony. These observations identify a role of ErbB4-dependent GABA activity in the hippocampus in synchronizing the hippocampal-prefrontal pathway and demonstrate that acute, dynamic ErbB4 signaling is required to command top-down attention. Because both neuregulin-1 and ErbB4 are susceptibility genes of schizophrenia and major depression, our study contributes to a better understanding of these disorders. VIDEO ABSTRACT. Copyright © 2018 Elsevier Inc. All rights reserved.

Intracellular recording, sensory field mapping, and culturing identified neurons in the leech, Hirudo medicinalis.

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Titlow, Josh; Majeed, Zana R; Nicholls, John G; Cooper, Robin L

2013-11-04

The freshwater leech, Hirudo medicinalis, is a versatile model organism that has been used to address scientific questions in the fields of neurophysiology, neuroethology, and developmental biology. The goal of this report is to consolidate experimental techniques from the leech system into a single article that will be of use to physiologists with expertise in other nervous system preparations, or to biology students with little or no electrophysiology experience. We demonstrate how to dissect the leech for recording intracellularly from identified neural circuits in the ganglion. Next we show how individual cells of known function can be removed from the ganglion to be cultured in a Petri dish, and how to record from those neurons in culture. Then we demonstrate how to prepare a patch of innervated skin to be used for mapping sensory or motor fields. These leech preparations are still widely used to address basic electrical properties of neural networks, behavior, synaptogenesis, and development. They are also an appropriate training module for neuroscience or physiology teaching laboratories.

Expression of oncogen c-erbB-2 (neu/HER-2) in human breast cancer

International Nuclear Information System (INIS)

Michelin, Severino C.; Mayo, Jose

2000-01-01

Breast cancer continues to be one of the leading causes of death from cancer among women and represents the most serious challenge to therapeutic control. Amplification and overexpression of the c-erbB-2 proto-oncogene occurs in as many as 30 % of all breast cancers and has been correlated with lymph node metastasis and poor prognosis in breast cancer patients. This gene know as neu, HER-2 or c-erbB-2 in among those most frequently altered in human cancer. It was first identified as a transforming gene activated in chemically induced rat neuroectodermal tumors. Early critical studies linked changes in erbB-2 expression and gene copy number to several human cancer, notably breast, ovarian and gastric cancer. Owing to its accessible location at the cell surface, erbB-2 is now under intensive scrutiny as a therapeutic target. In this review we will summarize the involvement of the c-erbB-2 gene in tumorigenesis. (author)

Differentially expressed genes in Hirudo medicinalis ganglia after acetyl-L-carnitine treatment.

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Federighi, Giuseppe; Macchi, Monica; Bernardi, Rodolfo; Scuri, Rossana; Brunelli, Marcello; Durante, Mauro; Traina, Giovanna

2013-01-01

Acetyl-L-carnitine (ALC) is a naturally occurring substance that, when administered at supra-physiological concentration, is neuroprotective. It is involved in membrane stabilization and in enhancement of mitochondrial functions. It is a molecule of considerable interest for its clinical application in various neural disorders, including Alzheimer's disease and painful neuropathies. ALC is known to improve the cognitive capability of aged animals chronically treated with the drug and, recently, it has been reported that it impairs forms of non-associative learning in the leech. In the present study the effects of ALC on gene expression have been analyzed in the leech Hirudo medicinalis. The suppression subtractive hybridisation methodology was used for the generation of subtracted cDNA libraries and the subsequent identification of differentially expressed transcripts in the leech nervous system after ALC treatment. The method detects differentially but also little expressed transcripts of genes whose sequence or identity is still unknown. We report that a single administration of ALC is able to modulate positively the expression of genes coding for functions that reveal a lasting effect of ALC on the invertebrate, and confirm the neuroprotective and neuromodulative role of the substance. In addition an important finding is the modulation of genes of vegetal origin. This might be considered an instance of ectosymbiotic mutualism.

Expressão imuno-histoquímica de c-erb-B2 e p53 em carcinomas gástricos Imunohistochemical expression of c-erb-B2 and p53 in gastric carcinomas

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Maria Dirlei F. S. Begnami

2005-08-01

Full Text Available INTRODUÇÃO: Em nosso meio, os carcinomas gástricos ainda são neoplasias bastante freqüentes e responsáveis por altas taxas de mortalidade. Recentemente, têm-se demonstrado a expressão de p53 e a amplificação do gene c-erb-B2 nos carcinomas gástricos. A relevância e o significado biológico destas alterações ainda não foram totalmente estabelecidos. OBJETIVO: Estudar as expressões imuno-histoquímicas de p53 e c-erb-B2 em 482 casos de carcinomas gástricos. MATERIAL E MÉTODOS: Foram construídos três blocos de tissue microarray (TMA utilizando-se duplicatas de 482 casos de carcinomas gástricos. Os cortes foram corados por hematoxilina e eosina (HE, tendo sido feita pesquisa para p53 e c-erb-B2. Foram considerados positivos para p53 os casos com marcação nuclear em mais de 10% das células tumorais. Para o c-erb-B2 foram considerados positivos os casos com marcação de membrana completa em mais de 10% das células tumorais. RESULTADOS: A expressão de p53 e c-erb-B2 foi observada em 30% e 12% dos casos, respectivamente. Em relação aos tipos histológicos observou-se correlação entre os carcinomas do tipo intestinal e a expressão de c-erb-B2 (p INTRODUCTION: Gastric cancer is one of the commonest cancers in our country being responsible for a high mortality rate. Recently, the expression of p53 and amplification of c-erb-B2 gene have been described in gastric carcinoma. The relevance and biological significance of these findings are not established yet. OBJECTIVE: The authors investigated p53, c-erb-B2 immunohistochemical expression in 482 cases of gastric carcinomas. MATERIAL AND METHODS: Tissue microarray (TMA blocks were designed using replicate samples of paraffin-embedded tissue from 482 gastric carcinomas. Sections were stained with HE, and antibodies to p53 and c-erb-B2. Cases were considered p53 positive if nuclear staining was detected in > 10% of the tumor cells. Cases were assessed c-erb-B2 positive if the

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

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

2011-08-10

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

Neratinib induces ErbB2 ubiquitylation and endocytic degradation via HSP90 dissociation in breast cancer cells.

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Zhang, Yingqiu; Zhang, Jinrui; Liu, Congcong; Du, Sha; Feng, Lu; Luan, Xuelin; Zhang, Yayun; Shi, Yulin; Wang, Taishu; Wu, Yue; Cheng, Wei; Meng, Songshu; Li, Man; Liu, Han

2016-11-28

Receptor tyrosine kinase ErbB2/HER2 is frequently observed to be overexpressed in human cancers, leading to over activation of downstream signaling modules. HER2 positive is a major type of breast cancer for which ErbB2 targeting is already proving to be an effective therapeutic strategy. Apart from antibodies against ErbB2, the small molecule tyrosine kinase inhibitor lapatinib has had successful clinical outcomes, and other inhibitors such as neratinib are currently undergoing clinical investigations. In this study we report the effects of lapatinib and neratinib on the mRNA and protein levels of the ErbB2 receptor. We provide evidence that neratinib-induced down regulation of ErbB2 occurs through ubiquitin-mediated endocytic sorting and lysosomal degradation. At the mechanistic level, neratinib treatment leads to HSP90 release from ErbB2 and its subsequent ubiquitylation and endocytic degradation. Our findings provide novel insights into the mechanism of ErbB2 inhibition by neratinib. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Identification of a novel antagonist of the ErbB1 receptor capable of inhibiting migration of human glioblastoma cells

DEFF Research Database (Denmark)

Staberg, Mikkel; Riemer, Christian; Xu, Ruodan

2013-01-01

B1 targeting peptide, termed Herfin-1, was designed based on a model of the tertiary structure of the EGF-EGFR ternary complex. The binding kinetics of this peptide were determined employing surface plasmon resonance analyses. ErbB1-4 expression and phosphorylation in human glioblastoma cell lines U...... processing. RESULTS: The present study shows that Herfin-1 functions as an ErbB1 antagonist. It binds to the extracellular domain of ErbB1 with a KD value of 361 nM. In U87 and U118 cells, both expressing high levels of ErbB1, Herfin-1 inhibits EGF-induced ErbB1 phosphorylation and cell migration....... Additionally, Herfin-1 was found to increase neurite outgrowth in cerebellar granule neurons, likely through the inhibition of a sustained weak ErbB1 activation. CONCLUSIONS: Targeting the ErbB1 receptor dimerization interface is a promising strategy to inhibit receptor activation in ErbB1-expressing glioma...

c-erbB-2 expression and benefit from adjuvant chemotherapy and radiotherapy of breast cancer

International Nuclear Information System (INIS)

Staal, O.; Sullivan, S.; Wingren, S.; Skoog, L.; Rutqvist, L.E.; Nordenskjoeld, B.; Carstensen, J.M.

1995-01-01

Frozen tissue from primary tumours of 152 premenopausal breast cancer patients, who participated in a trial comparing radiotherapy with adjuvant chemotherapy (cyclophosphamide, methotrexate, 5-fluorouracil, CMF), was analysed for c-erbB-2 protein expression, measured by flow cytometry. The relative risk of distant recurrence or death in the chemotherapy group as compared with the radiotherapy group was 3.0 (95% confidence interval (CI) 1.1-7.8) for patients whose tumours showed high c-erbB-2 levels and 0.87 (95% CI 0.43-1.7) for those with tumours with low levels of c-erbB-2 protein. Patients with highly proliferative tumours that did not overexpress c-erbB-2 benefited most, in terms of survival, from CMF. In addition, we found an increased risk of locoregional recurrence for tumours overexpressing c-erbB-2 when radiotherapy was replaced by chemotherapy. (author)

Decreased internalisation of erbB1 mutants in lung cancer is linked with a mechanism conferring sensitivity to gefitinib.

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Hendriks, B S; Griffiths, G J; Benson, R; Kenyon, D; Lazzara, M; Swinton, J; Beck, S; Hickinson, M; Beusmans, J M; Lauffenburger, D; de Graaf, D

2006-11-01

A majority of gefitinib (IRESSA)-responsive tumours in non-small cell lung cancer have been found to carry mutations in ErbB1. Previously, it has been observed that internalisation-deficient ErbB1 receptors are strong drivers of oncogenesis. Using a computational model of ErbB1 trafficking and signalling, it is found that a deficiency in ErbB1 internalisation is sufficient to explain the observed signalling phenotype of these gefitinib-responsive ErbB1 mutants in lung cancer cell lines. Experimental tests confirm that gefitinib-sensitive cell lines with and without ErbB1 mutations exhibit markedly slower internalisation rates than gefitinib-insensitive cell lines. Moreover, the computational model demonstrates that reduced ErbB1 internalisation rates are mechanistically linked to upregulated AKT signalling. Experimentally it is confirmed that impaired internalisation of ErbB1 is associated with increased AKT activity, which can be blocked by gefitinib. On the basis of these experimental and computational results, it is surmised that gefitinib sensitivity is a marker of a reliance on AKT signalling for cell survival that may be brought about by impaired ErbB1 internalisation.

A moderate elevation of circulating levels of IGF-I does not alter ErbB2 induced mammary tumorigenesis

International Nuclear Information System (INIS)

Dearth, Robert K; Kuiatse, Isere; Wang, Yu-Fen; Liao, Lan; Hilsenbeck, Susan G; Brown, Powel H; Xu, Jianming; Lee, Adrian V

2011-01-01

Epidemiological evidence suggests that moderately elevated levels of circulating insulin-like growth factor-I (IGF-I) are associated with increased risk of breast cancer in women. How circulating IGF-I may promote breast cancer incidence is unknown, however, increased IGF-I signaling is linked to trastuzumab resistance in ErbB2 positive breast cancer. Few models have directly examined the effect of moderately high levels of circulating IGF-I on breast cancer initiation and progression. The purpose of this study was to assess the ability of circulating IGF-I to independently initiate mammary tumorigenesis and/or accelerate the progression of ErbB2 mediated mammary tumor growth. We crossed heterozygous TTR-IGF-I mice with heterozygous MMTV-ErbB2 mice to generate 4 different genotypes: TTR-IGF-I/MMTV-ErbB2 (bigenic), TTR-IGF-I only, MMTV-ErbB2 only, and wild type (wt). Virgin females were palpated twice a week and harvested when tumors reached 1000 mm 3 . For study of normal development, blood and tissue were harvested at 4, 6 and 9 weeks of age in TTR-IGF-I and wt mice. TTR-IGF-I and TTR-IGF-I/ErbB2 bigenic mice showed a moderate 35% increase in circulating total IGF-I compared to ErbB2 and wt control mice. Elevation of circulating IGF-I had no effect upon pubertal mammary gland development. The transgenic increase in IGF-I alone wasn't sufficient to initiate mammary tumorigenesis. Elevated circulating IGF-I had no effect upon ErbB2-induced mammary tumorigenesis or metastasis, with median time to tumor formation being 30 wks and 33 wks in TTR-IGF-I/ErbB2 bigenic and ErbB2 mice respectively (p = 0.65). Levels of IGF-I in lysates from ErbB2/TTR-IGF-I tumors compared to ErbB2 was elevated in a similar manner to the circulating IGF-I, however, there was no effect on the rate of tumor growth (p = 0.23). There were no morphological differences in tumor type (solid adenocarcinomas) between bigenic and ErbB2 mammary glands. Using the first transgenic animal model to

Rev-Erb co-regulates muscle regeneration via tethered interaction with the NF-Y cistrome

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Ryan D. Welch

2017-07-01

Conclusions: Disrupting Rev-Erb activity in injured muscle accelerates regenerative muscle repair/differentiation through transcriptional de-repression of myogenic programs. Rev-Erb, therefore, may be a potent therapeutic target for a myriad of muscular disorders.

REV-ERB and ROR: therapeutic targets for treating myopathies

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Welch, Ryan D.; Flaveny, Colin A.

2017-08-01

Muscle is primarily known for its mechanical roles in locomotion, maintenance of posture, and regulation of cardiac and respiratory function. There are numerous medical conditions that adversely affect muscle, myopathies that disrupt muscle development, regeneration and protein turnover to detrimental effect. Skeletal muscle is also a vital secretory organ that regulates thermogenesis, inflammatory signaling and directs context specific global metabolic changes in energy substrate preference on a daily basis. Myopathies differ in the causative factors that drive them but share common features including severe reduction in quality of life and significantly increased mortality all due irrefutably to the loss of muscle mass. Thus far clinically viable approaches for preserving muscle proteins and stimulating new muscle growth without unwanted side effects or limited efficacy has been elusive. Over the last few decades, evidence has emerged through in vitro and in vivo studies that suggest the nuclear receptors REV-ERB and ROR might modulate pathways involved in myogenesis and mitochondrial biogenesis. Hinting that REV-ERB and ROR might be targeted to treat myopathies. However there is still a need for substantial investigation into the roles of these nuclear receptors in in vivo rodent models of degenerative muscle diseases and acute injury. Although exciting, REV-ERB and ROR have somewhat confounding roles in muscle physiology and therefore more studies utilizing in vivo models of skeletal muscle myopathies are needed. In this review we highlight the molecular forces driving some of the major degenerative muscular diseases and showcase two promising molecular targets that may have the potential to treat myopathies: ROR and REV-ERB.

Down-Regulation of Neuregulin1/ErbB4 Signaling in the Hippocampus Is Critical for Learning and Memory.

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Tian, Jia; Geng, Fei; Gao, Feng; Chen, Yi-Hua; Liu, Ji-Hong; Wu, Jian-Lin; Lan, Yu-Jie; Zeng, Yuan-Ning; Li, Xiao-Wen; Yang, Jian-Ming; Gao, Tian-Ming

2017-08-01

Hippocampal function is important for learning and memory, and dysfunction of the hippocampus has been linked to the pathophysiology of neuropsychiatric diseases such as schizophrenia. Neuregulin1 (NRG1) and ErbB4, two susceptibility genes for schizophrenia, reportedly modulate long-term potentiation (LTP) at hippocampal Schaffer collateral (SC)-CA1 synapses. However, little is known regarding the contribution of hippocampal NRG1/ErbB4 signaling to learning and memory function. Here, quantitative real-time PCR and Western blotting were used to assess the mRNA and protein levels of NRG1 and ErbB4. Pharmacological and genetic approaches were used to manipulate NRG1/ErbB4 signaling, following which learning and memory behaviors were evaluated using the Morris water maze, Y-maze test, and the novel object recognition test. Spatial learning was found to reduce hippocampal NRG1 and ErbB4 expression. The blockade of NRG1/ErbB4 signaling in hippocampal CA1, either by neutralizing endogenous NRG1 or inhibiting/ablating ErbB4 receptor activity, enhanced hippocampus-dependent spatial learning, spatial working memory, and novel object recognition memory. Accordingly, administration of exogenous NRG1 impaired those functions. More importantly, the specific ablation of ErbB4 in parvalbumin interneurons also improved learning and memory performance. The manipulation of NRG1/ErbB4 signaling in the present study revealed that NRG1/ErbB4 activity in the hippocampus is critical for learning and memory. These findings might provide novel insights on the pathophysiological mechanisms of schizophrenia and a new target for the treatment of Alzheimer's disease, which is characterized by a progressive decline in cognitive function.

Breast cancer metastasis driven by ErbB2 and 14-3-3ξ: A division of labor

OpenAIRE

Wang, Yingqun

2010-01-01

Metastasis remains the leading cause of cancer morbidity and mortality. ErbB2, a metastasis-promoting oncoprotein, is overexpressed in 50–60% of noninvasive ductal carcinoma in situ (DCIS). However, only 25% of invasive breast cancer (IBC) overexpress ErbB2, indicating that ErbB2 alone is not sufficient to drive metastasis and additional risk factors are necessary for the progression of ErbB2-overexpressing DCIS to IBC. A recent study published in Cancer Cell identified 14-3-3ξ as a risk fact...

ErbB3 mRNA leukocyte levels as a biomarker for major depressive disorder

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Milanesi Elena

2012-09-01

Full Text Available Abstract Background In recent years, the identification of peripheral biomarkers that are associated with psychiatric diseases, such as Major Depressive Disorder (MDD, has become relevant because these biomarkers may improve the efficiency of the differential diagnosis process and indicate targets for new antidepressant drugs. Two recent candidate genes, ErbB3 and Fgfr1, are growth factors whose mRNA levels have been found to be altered in the leukocytes of patients that are affected by bipolar disorder in a depressive state. On this basis, the aim of the study was to determine if ErbB3 and Fgfr1 mRNA levels could be a biomarkers of MDD. Methods We measured by Real Time PCR ErbB3 and Fgfr1 mRNA expression levels in leukocytes of MDD patients compared with controls. Successively, to assess whether ErbB3 mRNA levels were influenced by previous antidepressant treatment we stratified our patients sample in two cohorts, comparing drug-naive versus drug-free patients. Moreover, we evaluated the levels of the transcript in MDD patients after 12 weeks of antidepressant treatment, and in prefrontal cortex of rats stressed and treated with an antidepressant drug of the same class. Results These results showed that ErbB3 but not Fgfr1 mRNA levels were reduced in leukocytes of MDD patients compared to healthy subjects. Furthermore, ErbB3 levels were not affected by antidepressant treatment in either human or animal models Conclusions Our data suggest that ErbB3 might be considered as a biomarker for MDD and that its deficit may underlie the pathopsysiology of the disease and is not a consequence of treatment. Moreover the study supports the usefulness of leukocytes as a peripheral system for identifying biomarkers in psychiatric diseases.

Differentially expressed genes in Hirudo medicinalis ganglia after acetyl-L-carnitine treatment.

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Giuseppe Federighi

Full Text Available Acetyl-L-carnitine (ALC is a naturally occurring substance that, when administered at supra-physiological concentration, is neuroprotective. It is involved in membrane stabilization and in enhancement of mitochondrial functions. It is a molecule of considerable interest for its clinical application in various neural disorders, including Alzheimer's disease and painful neuropathies. ALC is known to improve the cognitive capability of aged animals chronically treated with the drug and, recently, it has been reported that it impairs forms of non-associative learning in the leech. In the present study the effects of ALC on gene expression have been analyzed in the leech Hirudo medicinalis. The suppression subtractive hybridisation methodology was used for the generation of subtracted cDNA libraries and the subsequent identification of differentially expressed transcripts in the leech nervous system after ALC treatment. The method detects differentially but also little expressed transcripts of genes whose sequence or identity is still unknown. We report that a single administration of ALC is able to modulate positively the expression of genes coding for functions that reveal a lasting effect of ALC on the invertebrate, and confirm the neuroprotective and neuromodulative role of the substance. In addition an important finding is the modulation of genes of vegetal origin. This might be considered an instance of ectosymbiotic mutualism.

Pertuzumab Increases 17-AAG-Induced Degradation of ErbB2, and This Effect Is Further Increased by Combining Pertuzumab with Trastuzumab

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Hughes, Juliana Bentes; Rødland, Marianne Skeie; Hasmann, Max; Madshus, Inger Helene; Stang, Espen

2012-01-01

ErbB2 is an important oncogenic protein involved in carcinogenesis of, among others, breast, gastric, and ovarian carcinoma. Over-expression of ErbB2 is found in almost 20% of breast cancers, and this results in proliferative and anti-apoptotic signalling. ErbB2 is therefore an important treatment target. Antibodies recognizing full-length ErbB2 are clinically established, and drugs targeting the ErbB2 stabilizing heat shock protein 90 (Hsp90) are under clinical evaluation. We have investigated effects of the ErbB2-binding antibodies trastuzumab and pertuzumab alone and in combination, as well as the effect of the antibodies in combination with the Hsp90 inhibitor 17-AAG. Our results confirm the notion that combination of different ErbB2-binding antibodies more efficiently down-regulates ErbB2 than does one antibody in isolation. Additionally, our data demonstrate that ErbB2 is most efficiently down-regulated upon incubation with anti-ErbB2 antibodies in combination with Hsp90 inhibitors. The combination of anti-ErbB2 antibodies, and especially the combination of antibodies with 17-AAG, did also increase the inhibition of Akt activation of either agent, which could suggest an anti-proliferative effect. In such case, combining these agents could be beneficial in treatment of tumors not responding to trastuzumab only. PMID:24281706

Pertuzumab Increases 17-AAG-Induced Degradation of ErbB2, and This Effect Is Further Increased by Combining Pertuzumab with Trastuzumab

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Juliana Bentes Hughes

2012-06-01

Full Text Available ErbB2 is an important oncogenic protein involved in carcinogenesis of, among others, breast, gastric, and ovarian carcinoma. Over-expression of ErbB2 is found in almost 20% of breast cancers, and this results in proliferative and anti-apoptotic signalling. ErbB2 is therefore an important treatment target. Antibodies recognizing full-length ErbB2 are clinically established, and drugs targeting the ErbB2 stabilizing heat shock protein 90 (Hsp90 are under clinical evaluation. We have investigated effects of the ErbB2-binding antibodies trastuzumab and pertuzumab alone and in combination, as well as the effect of the antibodies in combination with the Hsp90 inhibitor 17-AAG. Our results confirm the notion that combination of different ErbB2-binding antibodies more efficiently down-regulates ErbB2 than does one antibody in isolation. Additionally, our data demonstrate that ErbB2 is most efficiently down-regulated upon incubation with anti-ErbB2 antibodies in combination with Hsp90 inhibitors. The combination of anti-ErbB2 antibodies, and especially the combination of antibodies with 17-AAG, did also increase the inhibition of Akt activation of either agent, which could suggest an anti-proliferative effect. In such case, combining these agents could be beneficial in treatment of tumors not responding to trastuzumab only.

Characterization of the hormone-binding domain of the chicken c-erbA/thyroid hormone receptor protein

DEFF Research Database (Denmark)

Muñoz, A; Zenke, M; Gehring, U

1988-01-01

mutations present in the carboxy-terminal half of P75gag-v-erbA co-operate in abolishing hormone binding, and that the ligand-binding domain resides in a position analogous to that of steroid receptors. Furthermore, a point mutation that is located between the putative DNA and ligand-binding domains of P75......To identify and characterize the hormone-binding domain of the thyroid hormone receptor, we analyzed the ligand-binding capacities of proteins representing chimeras between the normal receptor and P75gag-v-erbA, the retrovirus-encoded form deficient in binding ligand. Our results show that several......gag-v-erbA and that renders it biologically inactive fails to affect hormone binding by the c-erbA protein. These results suggest that the mutation changed the ability of P75gag-v-erbA to affect transcription since it also had no effect on DNA binding. Our data also suggest that hormone...

Expression of Eag1 K+ channel and ErbBs in human pituitary adenomas: cytoskeleton arrangement patterns in cultured cells.

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del Pliego, Margarita González; Aguirre-Benítez, Elsa; Paisano-Cerón, Karina; Valdovinos-Ramírez, Irene; Rangel-Morales, Carlos; Rodríguez-Mata, Verónica; Solano-Agama, Carmen; Martín-Tapia, Dolores; de la Vega, María Teresa; Saldoval-Balanzario, Miguel; Camacho, Javier; Mendoza-Garrido, María Eugenia

2013-01-01

Pituitary adenomas can invade surrounded tissue, but the mechanism remains elusive. Ether à go-go-1 (Eag1) potassium channel and epidermal growth factor receptors (ErbB1 and ErbB2) have been associated to invasive phenotypes or poor prognosis in cancer patients. However, cells arrange their cytoskeleton in order to acquire a successful migration pattern. We have studied ErbBs and Eag1 expression, and cytoskeleton arrangements in 11 human pituitary adenomas. Eag1, ErbB1 and ErbB2 expression were studied by immunochemistry in tissue and cultured cells. The cytoskeleton arrangement was analyzed in cultured cells by immunofluorescence. Normal pituitary tissue showed ErbB2 expression and Eag1 only in few cells. However, Eag1 and ErbB2 were expressed in all the tumors analyzed. ErbB1 expression was observed variable and did not show specificity for a tumor characteristic. Cultured cells from micro- and macro-adenomas clinically functional organize their cytoskeleton suggesting a mesenchymal pattern, and a round leucocyte/amoeboid pattern from invasive clinically silent adenoma. Pituitary tumors over-express EGF receptors and the ErbB2 repeated expression suggests is a characteristic of adenomas. Eag 1 was express, in different extent, and could be a therapeutic target. The cytoskeleton arrangements observed suggest that pituitary tumor cells acquire different patterns: mesenchymal, and leucocyte/amoeboid, the last observed in the invasive adenomas. Amoeboid migration pattern has been associated with high invasion capacity.

ErbB receptors and cell polarity: New pathways and paradigms for understanding cell migration and invasion

International Nuclear Information System (INIS)

Feigin, Michael E.; Muthuswamy, Senthil K.

2009-01-01

The ErbB family of receptor tyrosine kinases is involved in initiation and progression of a number of human cancers, and receptor activation or overexpression correlates with poor patient survival. Research over the past two decades has elucidated the molecular mechanisms underlying ErbB-induced tumorigenesis, which has resulted in the development of effective targeted therapies. ErbB-induced signal transduction cascades regulate a wide variety of cell processes, including cell proliferation, apoptosis, cell polarity, migration and invasion. Within tumors, disruption of these core processes, through cooperative oncogenic lesions, results in aggressive, metastatic disease. This review will focus on the ErbB signaling networks that regulate migration and invasion and identify a potential role for cell polarity pathways during cancer progression

OCAM regulates embryonic spinal cord stem cell proliferation by modulating ErbB2 receptor.

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Loïc Deleyrolle

Full Text Available The proliferation and differentiation of neural stem cells are tightly controlled by intrinsic and extrinsic cues. Cell adhesion molecules are increasingly recognized as regulators of these processes. Here we report the expression of the olfactory cell adhesion molecule (OCAM/NCAM2/RNCAM during mouse spinal cord development and in neural stem cells cultured as neurospheres. OCAM is also weakly expressed in the dormant adult stem cell niche around the central canal and is overexpressed after spinal cord injury. Both transmembrane (TM and glycosylphosphatidylinositol (GPI-linked isoforms are present in neurospheres. Electron microscopy and internalisation experiments revealed a dynamic trafficking of OCAM between the membrane and intracellular compartments. After differentiation, OCAM remains in neurons and oligodendrocytes whereas no expression is detected in astrocytes. Using OCAM knockout (KO mice, we found that mutant spinal cord stem cells showed an increased proliferation and self-renewal rates although no effect on differentiation was observed. This effect was reversed by lentivirus-mediated re-introduction of OCAM. Mechanistically, we identified the ErbB2/Neu/HER2 protein as being implicated in the enhanced proliferation of mutant cells. ErbB2 protein expression and phosphorylation level were significantly increased in KO cells whereas no difference was observed at the mRNA level. Overexpression of ErbB2 in wild-type and mutant cells also increased their growth while reintroduction of OCAM in mutant cells reduced the level of phosphorylated ErbB2. These results indicate that OCAM exerts a posttranscriptional control on the ErbB2 signalling in spinal cord stem cells. This study adds further support for considering cell adhesion molecules as regulators of the ErbB signalling.

ERBS fuel addendum: Pollution reduction technology program small jet aircraft engines, phase 3

Science.gov (United States)

Bruce, T. W.; Davis, F. G.; Kuhn, T. E.; Mongia, H. C.

1982-01-01

A Model TFE731-2 engine with a low emission, variable geometry combustion system was tested to compare the effects of operating the engine on Commercial Jet-A aviation turbine fuel and experimental referee broad specification (ERBS) fuels. Low power emission levels were essentially identical while the high power NOx emission indexes were approximately 15% lower with the EBRS fuel. The exhaust smoke number was approximately 50% higher with ERBS at the takeoff thrust setting; however, both values were still below the EPA limit of 40 for the Model TFE731 engine. Primary zone liner wall temperature ran an average of 25 K higher with ERBS fuel than with Jet-A. The possible adoption of broadened proprties fuels for gas turbine applications is suggested.

Microsurgeon Hirudo medicinalis as a Natural Bioshuttle for Spontaneous Mass Vaccination against Influenza A Virus

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Sajjad Khani

2011-09-01

Full Text Available Introduction: Recent report on existence of a stem region of hemagglutinin has arisen new hopes for vaccination of influenza A as it consist of a conserve fusion peptide shared across several influenza subtypes and can be targeted by human immune system. Methods: Given that traditional vaccination based on live attenuated viruses often fails to surpass such viral infection, a great deal of attention has been devoted to develop a safe yet efficient system for vaccination influenza A. We believe that a natural bioshuttle can be recruited for spontaneous mass vaccination. Results: Thus, here, we hypothesize that a bioengineered transgenic Hirudo medicinalis can be considered as an alive bioshuttle for in-situ vaccination against influenza A virus. By introducing the designated gene(s encoding the target fragment (i.e., stem region of hemagglutinin, this microsurgeon can act as a rapid microproducer of viral proteins for in-house mass vaccination through imparting the necessary proteins such as those, naturally presented in leech's saliva. Conclusion: This peculiar bioshuttle can be easily exploited as a medical modality choice at home resulting in greater patient compliance.

Comprehensive Binary Interaction Mapping of SH2 Domains via Fluorescence Polarization Reveals Novel Functional Diversification of ErbB Receptors

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Ciaccio, Mark F.; Chuu, Chih-pin; Jones, Richard B.

2012-01-01

First-generation interaction maps of Src homology 2 (SH2) domains with receptor tyrosine kinase (RTK) phosphosites have previously been generated using protein microarray (PM) technologies. Here, we developed a large-scale fluorescence polarization (FP) methodology that was able to characterize interactions between SH2 domains and ErbB receptor phosphosites with higher fidelity and sensitivity than was previously achieved with PMs. We used the FP assay to query the interaction of synthetic phosphopeptides corresponding to 89 ErbB receptor intracellular tyrosine sites against 93 human SH2 domains and 2 phosphotyrosine binding (PTB) domains. From 358,944 polarization measurements, the affinities for 1,405 unique biological interactions were determined, 83% of which are novel. In contrast to data from previous reports, our analyses suggested that ErbB2 was not more promiscuous than the other ErbB receptors. Our results showed that each receptor displays unique preferences in the affinity and location of recruited SH2 domains that may contribute to differences in downstream signaling potential. ErbB1 was enriched versus the other receptors for recruitment of domains from RAS GEFs whereas ErbB2 was enriched for recruitment of domains from tyrosine and phosphatidyl inositol phosphatases. ErbB3, the kinase inactive ErbB receptor family member, was predictably enriched for recruitment of domains from phosphatidyl inositol kinases and surprisingly, was enriched for recruitment of domains from tyrosine kinases, cytoskeletal regulatory proteins, and RHO GEFs but depleted for recruitment of domains from phosphatidyl inositol phosphatases. Many novel interactions were also observed with phosphopeptides corresponding to ErbB receptor tyrosines not previously reported to be phosphorylated by mass spectrometry, suggesting the existence of many biologically relevant RTK sites that may be phosphorylated but below the detection threshold of standard mass spectrometry procedures. This

Comprehensive binary interaction mapping of SH2 domains via fluorescence polarization reveals novel functional diversification of ErbB receptors.

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Ronald J Hause

Full Text Available First-generation interaction maps of Src homology 2 (SH2 domains with receptor tyrosine kinase (RTK phosphosites have previously been generated using protein microarray (PM technologies. Here, we developed a large-scale fluorescence polarization (FP methodology that was able to characterize interactions between SH2 domains and ErbB receptor phosphosites with higher fidelity and sensitivity than was previously achieved with PMs. We used the FP assay to query the interaction of synthetic phosphopeptides corresponding to 89 ErbB receptor intracellular tyrosine sites against 93 human SH2 domains and 2 phosphotyrosine binding (PTB domains. From 358,944 polarization measurements, the affinities for 1,405 unique biological interactions were determined, 83% of which are novel. In contrast to data from previous reports, our analyses suggested that ErbB2 was not more promiscuous than the other ErbB receptors. Our results showed that each receptor displays unique preferences in the affinity and location of recruited SH2 domains that may contribute to differences in downstream signaling potential. ErbB1 was enriched versus the other receptors for recruitment of domains from RAS GEFs whereas ErbB2 was enriched for recruitment of domains from tyrosine and phosphatidyl inositol phosphatases. ErbB3, the kinase inactive ErbB receptor family member, was predictably enriched for recruitment of domains from phosphatidyl inositol kinases and surprisingly, was enriched for recruitment of domains from tyrosine kinases, cytoskeletal regulatory proteins, and RHO GEFs but depleted for recruitment of domains from phosphatidyl inositol phosphatases. Many novel interactions were also observed with phosphopeptides corresponding to ErbB receptor tyrosines not previously reported to be phosphorylated by mass spectrometry, suggesting the existence of many biologically relevant RTK sites that may be phosphorylated but below the detection threshold of standard mass spectrometry

Neratinib, an irreversible ErbB receptor tyrosine kinase inhibitor, in patients with advanced ErbB2-positive breast cancer.

Science.gov (United States)

Burstein, Harold J; Sun, Yan; Dirix, Luc Y; Jiang, Zefei; Paridaens, Robert; Tan, Antoinette R; Awada, Ahmad; Ranade, Anantbhushan; Jiao, Shunchang; Schwartz, Gary; Abbas, Richat; Powell, Christine; Turnbull, Kathleen; Vermette, Jennifer; Zacharchuk, Charles; Badwe, Rajendra

2010-03-10

Neratinib is an oral, irreversible pan-ErbB receptor tyrosine kinase inhibitor. The efficacy and safety of neratinib were evaluated in two cohorts of patients with advanced ErbB2-positive breast cancer-those with and those without prior trastuzumab treatment-in an open-label, multicenter, phase II trial. Patients in the two cohorts (prior trastuzumab, n = 66; no prior trastuzumab, n = 70) received oral neratinib 240 mg once daily. The primary end point was the 16-week progression-free survival (PFS) rate for the evaluable population (prior trastuzumab, n = 63; no prior trastuzumab, n = 64), as assessed by independent review. The 16-week PFS rates were 59% for patients with prior trastuzumab treatment and 78% for patients with no prior trastuzumab treatment. Median PFS was 22.3 and 39.6 weeks, respectively. Objective response rates were 24% among patients with prior trastuzumab treatment and 56% in the trastuzumab-naïve cohort. The most common adverse events were diarrhea, nausea, vomiting, and fatigue. Diarrhea was the most frequent grades 3 to 4 adverse event, occurring in 30% of patients with prior trastuzumab treatment and in 13% of patients with no prior trastuzumab treatment, which prompted dose reductions in 29% and 4% of patients, respectively, but treatment discontinuation in only one patient. No neratinib-related, grades 3 or 4 cardiotoxicity was reported. Oral neratinib showed substantial clinical activity and was reasonably well tolerated among both heavily pretreated and trastuzumab-naïve patients who had advanced, ErbB2-positive breast cancer. Diarrhea was the most common adverse effect but was manageable with antidiarrheal agents and dose modification.

The ErbB family and androgen receptor signaling are targets of Celecoxib in prostate cancer.

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Brizzolara, Antonella; Benelli, Roberto; Venè, Roberta; Barboro, Paola; Poggi, Alessandro; Tosetti, Francesca; Ferrari, Nicoletta

2017-08-01

Inflammation plays a central role in prostate cancer (PCa) development through significant crosstalk between the COX-2-ErbB family receptor network and androgen receptor (AR)-EGFR signaling pathways. The purpose of this work was to determine the ability of the COX-2 inhibitor Celecoxib to modulate the EGFR-AR signaling pathway in androgen-dependent PCa cells and to provide a rationale for its beneficial use in chemopreventive strategies. Functional studies of Celecoxib activity were performed on LNCaP prostate cancer cells. Western blotting, gene expression analysis, dual-luciferase reporter assay and ELISA were applied to assess the Celecoxib mechanisms of action. We found that Celecoxib, through EGF and amphiregulin (AREG) induction, caused EGFR and ErbB2 activation and consequent degradation associated with the inhibition of androgenic signaling. By upregulating the E3 ubiquitin ligase Nrdp1, Celecoxib also efficiently downregulated ErbB3, which is strongly implicated in castration-resistant prostate cancer. Lastly, Celecoxib directly regulated AR transcription and translation independent of ErbB activation by downregulating the RNA binding protein heterogeneous nuclear ribonucleoprotein K (hnRNP K). The simultaneous suppression of ErbB kinases and androgen signaling by Celecoxib represents a novel strategy to interrupt the vicious cycle of AR/ErbB cross-talk with the primary purpose of undermining their resilient signaling in prostate cancer progression. Our data provide important premises for the chemopreventive use of Celecoxib in the clinical management of prostate cancer. Copyright © 2017 Elsevier B.V. All rights reserved.

Data on the effect of in vivo knockdown using artificial ErbB3 miRNA on Remak bundle structure

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Yuki Miyamoto

2017-06-01

Full Text Available Mature Schwann cells, the peripheral nervous system (PNS glial cells, have two major roles for neuronal axons (Bunge, 1993 [1]. For large diameter axons, Schwann cells form myelin sheaths with multiple layers. For small diameter axons, they form Remak bundle composed only of single layer of the Schwann cell plasma membrane. In the PNS, ErbB3 forms a dimer with ErbB2 on the Schwann cell plasma membrane. ErbB3 plays a key role in myelination by myelinating Schwann cells, that is to say, its role in myelin thickness. Herein we provide the data regarding the effect of in vivo knockdown of ErbB3 on the thickness between an axon and a neighboring axon in Remak bundle, which is formed by non-myelinating Schwann cells. Since ErbB3 knockout mice are embryonically lethal, Schwann cell lineage-specific transgenic mice transcribing ErbB3 shRNA with an artificial miRNA backbone were generated and used in these experiments (Torii et al., 2014 [2].

Imunoexpressão do c-erbB-2 nas lesões epiteliais proliferativas intraductais da mama de mulheres Immunoexpression of c-erbB-2 in intraductal proliferative lesions of the female breast

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Agliberto Barbosa de Oliveira

2004-09-01

Full Text Available OBJETIVOS: Alterações genéticas são relacionadas à gênese e progressão do câncer. Neoplasias de vários órgãos expressam o oncogene c-erbB-2. Nas proliferações intraductais da mama tem sido avaliado como fator de risco para o desenvolvimento de câncer. Foram avaliadas a imunoexpressão do c-erbB-2 em lesões epiteliais proliferativas intraductais e as possíveis correlações com características anatomopatológicas do carcinoma ductal "in situ" (CDIS. MÉTODOS: Foi utilizado material de arquivo, amostras teciduais fixadas em formalina e incluídas em blocos de parafina de 88 mulheres. Destas, 51 com CDIS e 37 com hiperplasia ductal sem atipias (HDT. A idade variou de 35 a 76 anos. Revisados todos os casos, verificou-se: o grau nuclear, a presença de necrose, o subtipo histológico predominante e sua extensão. Obteve-se material suficiente para o estudo imunohistoquímico do c-erbB-2 de 84 sujeitos do estudo. RESULTADOS: Não foi observada a expressão do oncogene nas hiperplasias sem atipias e nos tecidos adjacentes a todas amostras teciduais. A expressão do c-erbB-2 foi verificada em nove (19,1% dos CDIS (p= 0,0001. A imunoexpressão não se relacionou à extensão das lesões. A imunoexpressão do c-erbB-2 no CDIS correlacionou-se com subtipo histológico (p=0,019, com a presença de necrose (p=0,0066, com o grau nuclear (p=0,0084 e com a Classificação de Van Nuys (p=0,039. CONCLUSÕES: A expressão do c-erbB-2 foi estatisticamente significante nas lesões proliferativas de risco (CDIS e correlacionou-se com características histopatológicas: alto grau nuclear, presença de necrose, subtipo comedo. Não houve expressão nas hiperplasias sem atipias e tecidos adjacentes.OBJECTIVES: Genetic modifications are related to genesis and development of cancer. Neoplasias in various organs express the c-erbB-2 oncogene. In intraductal proliferations of the breast it has been assessed as a risk factor for subsequent development of

c-erbB2 and topoisomerase IIα protein expression independently predict poor survival in primary human breast cancer: a retrospective study

International Nuclear Information System (INIS)

Fritz, Peter; Cabrera, Cristina M; Dippon, Jürgen; Gerteis, Andreas; Simon, Wolfgang; Aulitzky, Walter E; Kuip, Heiko van der

2005-01-01

c-erbB2 (also known as HER-2/neu) and topoisomerase IIα are frequently overexpressed in breast cancer. The aim of the study was to analyze retrospectively whether the expression of c-erbB2 and topoisomerase IIα protein influences the long-term outcome of patients with primary breast cancer. In this study c-erbB2 and topoisomerase IIα protein were evaluated by immunohistochemistry in formalin-fixed paraffin-embedded tissue from 225 samples of primary breast cancer, obtained between 1986 and 1998. The prognostic value of these markers was analyzed. Of 225 primary breast tumor samples, 78 (34.7%) showed overexpression of either c-erbB2 (9.8%) or topoisomerase IIα protein (24.9%), whereas in 21 tumors (9.3%) both proteins were found to be overexpressed. Patients lacking both c-erbB2 and topoisomerase IIα overexpression had the best long-term survival. Overexpression of either c-erbB2 or topoisomerase IIα was associated with shortened survival, whereas patients overexpressing both c-erbB2 and topoisomerase IIα showed the worst disease outcome (P < 0.0001). Treatment with anthracyclines was not capable of reversing the negative prognostic impact of topoisomerase IIα or c-erbB2 overexpression. The results of this exploratory study suggest that protein expression of c-erbB2 and topoisomerase IIα in primary breast cancer tissues are independent prognostic factors and are not exclusively predictive factors for anthracycline response in patients with primary breast cancer

Endocytic down-regulation of ErbB2 is stimulated by cleavage of its C-terminus

DEFF Research Database (Denmark)

Lerdrup, Mads; Bruun, Silas; Grandal, Michael Vibo

2007-01-01

inhibition of HSP90 with geldanamycin this cleavage is accompanied by proteasome-dependent endocytosis of ErbB2. However, it is unknown whether C-terminal cleavage is linked to endocytosis. To study ErbB2 cleavage and endocytic trafficking, we fused yellow fluorescent protein (YFP) and cyan fluorescent...

Preliminary study of p53 and c-erbB-2 expression in gallbladder cancer in Indian patients

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Singh Usha

2006-05-01

Full Text Available Abstract Background The inactivation of the tumour suppressor gene and activation of the proto-oncogene are the key steps in the development of the human cancer. The p53 and c-erbB-2 are the best examples of it. In the present study, our aim was to determine the role of these genes in the carcinogenesis of gallbladder by immunohistochemistry. Methods In all 78 consecutive patients of gall bladder diseases were studied for p53 and c-erbB-2 expression immunohistochemically and their expression was correlated with the age, grades and stages of the disease and presence of stone. An informed consent was obtained in each case. Chi square and z test were applied to see the association of p53 and c-erbB-2 over expression with other clinicopathological factors. Results Eight (20% patients of gall bladder cancer were positive for p53 expression and 10 (25% patients for c-erbB-2. The p53 positivity increased with increasing grade while cerbB-2 positivity decreased with increasing grade of gall bladder cancer. Mean age in cerbB-2 positive cases were lesser as compared to negative cases while p53 did not show such association with age. Conclusion Only one case of gall bladder cancer co-expressed the p53 and c-erbB-2, thereby suggesting that p53 and c-erbB-2 may have independent role in carcinogenesis of gall bladder cancer. c-erbB-2 over expression in adenoma and younger age group indicates its role as an early event in carcinogenesis of gallbladder. However study of larger sample is required to further validate the results.

Clinical Significance of ErbB Receptor Family in Urothelial Carcinoma of the Bladder: A Systematic Review and Meta-Analysis

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Yuh-Shyan Tsai

2012-01-01

Full Text Available The prognostic importance of examining ErbB receptor family expression in human bladder cancer remains uncertain. Using published evidence, we examined the clinical value and the updated results of clinical trials targeting ErbB receptor family members. Twenty-seven articles from 65 references related to ErbB receptor expression assessment in bladder cancer were reviewed. The estimates included the association significance, hazard ratios, and 95% confidence intervals (CIs from actuarial curves and survival analyses. A meta-analysis was done on those reports using univariate log-rank tests or a Cox-regression model. The methods of analysis and study subjects chosen varied widely among studies. The overall risks of disease progression for patients with EGFR or ErbB2 overexpression were 4.5 (95% CI: 2.5–8.4 and 1.1 (95% CI: 0.6–1.9, and the risks of mortality were 3.0 (95% CI: 1.6–5.9 and 1.1 (95% CI: 1.0–1.2, respectively. However, the significance of coexpression patterns of the ErbB receptor family remains controversial. None of six clinical trials yielded convincing results for blockading ErbB receptor signaling in urothelial carcinoma. The results of this analysis suggest that assessing co-expression patterns of the ErbB family may provide better prognostic information for bladder cancer patients.

Comparison of ERBS orbit determination accuracy using batch least-squares and sequential methods

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Oza, D. H.; Jones, T. L.; Fabien, S. M.; Mistretta, G. D.; Hart, R. C.; Doll, C. E.

1991-10-01

The Flight Dynamics Div. (FDD) at NASA-Goddard commissioned a study to develop the Real Time Orbit Determination/Enhanced (RTOD/E) system as a prototype system for sequential orbit determination of spacecraft on a DOS based personal computer (PC). An overview is presented of RTOD/E capabilities and the results are presented of a study to compare the orbit determination accuracy for a Tracking and Data Relay Satellite System (TDRSS) user spacecraft obtained using RTOS/E on a PC with the accuracy of an established batch least squares system, the Goddard Trajectory Determination System (GTDS), operating on a mainframe computer. RTOD/E was used to perform sequential orbit determination for the Earth Radiation Budget Satellite (ERBS), and the Goddard Trajectory Determination System (GTDS) was used to perform the batch least squares orbit determination. The estimated ERBS ephemerides were obtained for the Aug. 16 to 22, 1989, timeframe, during which intensive TDRSS tracking data for ERBS were available. Independent assessments were made to examine the consistencies of results obtained by the batch and sequential methods. Comparisons were made between the forward filtered RTOD/E orbit solutions and definitive GTDS orbit solutions for ERBS; the solution differences were less than 40 meters after the filter had reached steady state.

Comparison of ERBS orbit determination accuracy using batch least-squares and sequential methods

Science.gov (United States)

Oza, D. H.; Jones, T. L.; Fabien, S. M.; Mistretta, G. D.; Hart, R. C.; Doll, C. E.

1991-01-01

The Flight Dynamics Div. (FDD) at NASA-Goddard commissioned a study to develop the Real Time Orbit Determination/Enhanced (RTOD/E) system as a prototype system for sequential orbit determination of spacecraft on a DOS based personal computer (PC). An overview is presented of RTOD/E capabilities and the results are presented of a study to compare the orbit determination accuracy for a Tracking and Data Relay Satellite System (TDRSS) user spacecraft obtained using RTOS/E on a PC with the accuracy of an established batch least squares system, the Goddard Trajectory Determination System (GTDS), operating on a mainframe computer. RTOD/E was used to perform sequential orbit determination for the Earth Radiation Budget Satellite (ERBS), and the Goddard Trajectory Determination System (GTDS) was used to perform the batch least squares orbit determination. The estimated ERBS ephemerides were obtained for the Aug. 16 to 22, 1989, timeframe, during which intensive TDRSS tracking data for ERBS were available. Independent assessments were made to examine the consistencies of results obtained by the batch and sequential methods. Comparisons were made between the forward filtered RTOD/E orbit solutions and definitive GTDS orbit solutions for ERBS; the solution differences were less than 40 meters after the filter had reached steady state.

Characterization of the promoter region of the human c-erbB-2 protooncogene

International Nuclear Information System (INIS)

Ishii, S.; Imamoto, F.; Yamanashi, Y.; Toyoshima, K.; Yamamoto, T.

1987-01-01

Three overlapping genomic clones that contain the 5'-terminal portion of the human c-erbB-2 gene (ERBB2) were isolated. The promoter region was identified by nuclease S1 mapping with c-erbB-2 mRNA. Seven transcriptional start sites were identified. DNA sequence analysis showed that the promoter region contains a TATA box and a CAAT box about 30 and 80 base pairs (bp), respectively, upstream of the most downstream RNA initiation site. Two putative binding sites for transcription factor Sp1 were identified about 50 and 110 bp upstream of the CAAT box, and six GGA repeats were found between the CAAT box and the TATA box. This region had strong promoter activity when placed upstream of the bacterial chloramphenicol acetyltransferase gene and transfected into monkey CV-1 cells. These data indicate that the promoter of the human c-erbB-2 protooncogene is different from that of the protooncogene c-erbB-1 (epidermal growth factor receptor gene), which does not contain either a TATA box or a CAAT box. Comparison of the promoter sequences and activities of the two protooncogenes should be helpful in analysis of the regulatory mechanism of expression of their gene products, which are growth-factor receptors

Inhibition of ErbB2 by receptor tyrosine kinase inhibitors causes myofibrillar structural damage without cell death in adult rat cardiomyocytes

International Nuclear Information System (INIS)

Pentassuglia, Laura; Graf, Michael; Lane, Heidi; Kuramochi, Yukio; Cote, Gregory; Timolati, Francesco; Sawyer, Douglas B.; Zuppinger, Christian; Suter, Thomas M.

2009-01-01

Inhibition of ErbB2 (HER2) with monoclonal antibodies, an effective therapy in some forms of breast cancer, is associated with cardiotoxicity, the pathophysiology of which is poorly understood. Recent data suggest, that dual inhibition of ErbB1 (EGFR) and ErbB2 signaling is more efficient in cancer therapy, however, cardiac safety of this therapeutic approach is unknown. We therefore tested an ErbB1-(CGP059326) and an ErbB1/ErbB2-(PKI166) tyrosine kinase inhibitor in an in-vitro system of adult rat ventricular cardiomyocytes and assessed their effects on 1. cell viability, 2. myofibrillar structure, 3. contractile function, and 4. MAPK- and Akt-signaling alone or in combination with Doxorubicin. Neither CGP nor PKI induced cardiomyocyte necrosis or apoptosis. PKI but not CGP caused myofibrillar structural damage that was additive to that induced by Doxorubicin at clinically relevant doses. These changes were associated with an inhibition of excitation-contraction coupling. PKI but not CGP decreased p-Erk1/2, suggesting a role for this MAP-kinase signaling pathway in the maintenance of myofibrils. These data indicate that the ErbB2 signaling pathway is critical for the maintenance of myofibrillar structure and function. Clinical studies using ErbB2-targeted inhibitors for the treatment of cancer should be designed to include careful monitoring for cardiac dysfunction.

[Immunoexpression of c-erbB-2 in intraductal proliferative lesions of the female breast].

Science.gov (United States)

Oliveira, Agliberto Barbosa de; De Luca, Laurival Antônio; Carvalho, Grigna Teixeira; Arias, Victor Eduardo Arua; Carvalho, Lídia Raquel de; Assunção, Maria do Carmo

2004-01-01

Genetic modifications are related to genesis and development of cancer. Neoplasias in various organs express the c-erbB-2 oncogene. In intraductal proliferations of the breast it has been assessed as a risk factor for subsequent development of carcinoma. The c-erbB-2 immunoexpression in intraductal epithelial proliferations and the relationship with histopathological characteristics of ductal carcinoma in situ (DCIS) were evaluated. File material from 88 women, which were tissue samples formalin-fixed, paraffin-embedded blocks, was used. Of these 51 presented with DCIS and 37 with ductal hyperplasia without atypia. Ages of the women ranged from 35 to 76 years. All cases were reviewed and nuclear grade, presence of necrosis, preponderance of histological subtype and its extension were verified. Specimens were obtained for the c-erB-2 immunohistochemical study of 84 of the women in question. No expression of the oncogene was verified in the hyperplasias without atypias and in tissues adjacent to all tissue samples. Expression of c-erbB-2 was verified in 9 (19.1%) of the DCIS (p = 0.0001). Immunoexpression was not related to the extension of the lesions. The c-erbB-2 immunoexpression in DCIS was correlated to the histological subtype (p = 0.019), necrosis (p = 0.0066), nuclear grade (p = 0.0084) and Van Nuys Classification (p = 0.039). Expression of c-erbB-2 was significant in proliferative lesions with risk (DCIS) and was correlated to histopathological characteristics: high nuclear grade, presence of necrosis and comedy subtype. There was no expression in the hyperplasias without atypias and adjacent tissues.

Overexpression of c-erbB-2 and loss of p16 have molecular diagnostic relevance but no prognostic value in lung cancer.

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Feng, Xiao-li; Li, Ling; Gao, Yan-ning; Zhang, Jian-jun; Xiao, Ting; Ying, Jian-ming; Gao, Ji-dong; Sun, Yun-tian; Cheng, Shu-jun

2011-03-01

This study was designed to evaluate the expression of C-erbB-2 and p16 in lung cancers using tissue microarray technology and to determine their clinical and pathological significance. Immunohistochemical C-erbB-2 and p16 expressions and their associations with clinical and pathological features were analyzed in two tissue microarrays. The membranous and cytoplasmic expression rates of C-erbB-2 were 40.5 and 66.5% in non-small cell lung cancers (NSCLCs), and 0 and 9.5% in small cell lung cancers (SCLCs), respectively. The nuclear and cytoplasmic expression rates of p16 were 11.5 and 32.2% in NSCLs, and 45 and 80% in SCLCs, respectively. The cytoplasmic expression of both C-erbB-2 and p16 was more frequent than the membranous expression of C-erbB-2 and the nuclear expression of p16. The rates of overexpression of C-erbB-2 and loss of p16 expression were significantly higher in NSCLCs than in SCLCs (P < 0.05). Neither C-erbB-2 nor p16 expression was significantly associated with age, tumor grade or stage, presence of lymph node metastasis or survival duration. The abnormal expressions of p16 and C-erbB-2 may play a role in the progression of lung cancers. The variations in the expression patterns of C-erbB-2 and p16 between NSCLCs and SCLCs may aid the molecular classification of lung cancer. The abnormal expression of p16 may be involved in the development of NSCLCs, and the overexpression of C-erbB-2 in NSCLCs indicates that it can be a candidate target for gene therapy.

Small molecule ErbB inhibitors decrease proliferative signaling and promote apoptosis in philadelphia chromosome-positive acute lymphoblastic leukemia.

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Mary E Irwin

Full Text Available The presence of the Philadelphia chromosome in patients with acute lymphoblastic leukemia (Ph(+ALL is a negative prognostic indicator. Tyrosine kinase inhibitors (TKI that target BCR/ABL, such as imatinib, have improved treatment of Ph(+ALL and are generally incorporated into induction regimens. This approach has improved clinical responses, but molecular remissions are seen in less than 50% of patients leaving few treatment options in the event of relapse. Thus, identification of additional targets for therapeutic intervention has potential to improve outcomes for Ph+ALL. The human epidermal growth factor receptor 2 (ErbB2 is expressed in ~30% of B-ALLs, and numerous small molecule inhibitors are available to prevent its activation. We analyzed a cohort of 129 ALL patient samples using reverse phase protein array (RPPA with ErbB2 and phospho-ErbB2 antibodies and found that activity of ErbB2 was elevated in 56% of Ph(+ALL as compared to just 4.8% of Ph(-ALL. In two human Ph+ALL cell lines, inhibition of ErbB kinase activity with canertinib resulted in a dose-dependent decrease in the phosphorylation of an ErbB kinase signaling target p70S6-kinase T389 (by 60% in Z119 and 39% in Z181 cells at 3 µM. Downstream, phosphorylation of S6-kinase was also diminished in both cell lines in a dose-dependent manner (by 91% in both cell lines at 3 µM. Canertinib treatment increased expression of the pro-apoptotic protein Bim by as much as 144% in Z119 cells and 49% in Z181 cells, and further produced caspase-3 activation and consequent apoptotic cell death. Both canertinib and the FDA-approved ErbB1/2-directed TKI lapatinib abrogated proliferation and increased sensitivity to BCR/ABL-directed TKIs at clinically relevant doses. Our results suggest that ErbB signaling is an additional molecular target in Ph(+ALL and encourage the development of clinical strategies combining ErbB and BCR/ABL kinase inhibitors for this subset of ALL patients.

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

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Jesus Eliane C.

2005-01-01

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

A peptide antagonist of the ErbB1 receptor inhibits receptor activation, tumor cell growth and migration in vitro and xenograft tumor growth in vivo

DEFF Research Database (Denmark)

Xu, Ruodan; Povlsen, Gro Klitgaard; Soroka, Vladislav

2010-01-01

The epidermal growth factor family of receptor tyrosine kinases (ErbBs) plays essential roles in tumorigenesis and cancer disease progression, and therefore has become an attractive target for structure-based drug design. ErbB receptors are activated by ligand-induced homo- and heterodimerization...... constitutes part of the dimerization arm of ErbB3. Inherbin3 binds to the extracellular domains of all four ErbB receptors, with the lowest peptide binding affinity for ErbB4. Inherbin3 functions as an antagonist of epidermal growth factor (EGF)-ErbB1 signaling. We show that Inherbin3 inhibits EGF-induced Erb....... Structural studies have revealed that ErbB receptor dimers are stabilized by receptor-receptor interactions, primarily mediated by a region in the second extracellular domain, termed the "dimerization arm". The present study is the first biological characterization of a peptide, termed Inherbin3, which...

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

DEFF Research Database (Denmark)

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

2012-01-01

Aberrant ErbB2 receptor tyrosine kinase activation in breast cancer is strongly linked to an invasive disease. The molecular basis of ErbB2-driven invasion is largely unknown. We show that cysteine cathepsins B and L are elevated in ErbB2 positive primary human breast cancer and function...... as effectors of ErbB2-induced invasion in vitro. We identify Cdc42-binding protein kinase beta, extracellular regulated kinase 2, p21-activated protein kinase 4, and protein kinase C alpha as essential mediators of ErbB2-induced cysteine cathepsin expression and breast cancer cell invasiveness. The identified...

Lack of prognostic significance of C-erbB-2 expression in low- and high- grade astrocytomas.

Science.gov (United States)

Muallaoglu, Saik; Besen, Ali Ayberk; Ata, Alper; Mertsoylu, Huseyin; Arican, Ali; Kayaselcuk, Fazilet; Ozyilkan, Ozgur

2014-01-01

Astrocytic tumors, the most common primary glial tumors of the central nervous system, are classified from low to high grade according to the degree of anaplasia and presence of necrosis. Despite advances in therapeutic management of high grade astrocytic tumors, prognosis remains poor. In the present study, the frequency and prognostic significance of c-erb-B2 in astrocytic tumors was investigated. Records of 72 patients with low- and high-grade astrocytic tumors were evaluated. The expression of C-erbB-2 was determined immunohistochemically and intensity was recorded as 0 to 3+. Tumors with weak staining (1+) or no staining (0) were considered Her-2 negative, while tumors with moderate (2+) and strong (3+) staining were considered Her-2 positive. Of the 72 patients, 41 (56.9%) had glioblastoma (GBM), 10 (13.9%) had diffuse astrocytoma, 15 (20.8%) had anaplastic astrocytoma, 6 (8.3%) had pilocytic astrocytoma. C-erbB-2 overexpression was detected in the tumor specimens of 17 patients (23.6%). Six (8.3%) tumors, all GBMs, exhibited strong staining, 2 (2.7%) specimens, both GBMs, exhibited moderate staining, and 9 specimens, 5 of them GBMs (12.5%), exhibited weak staining. No staining was observed in diffuse astrocytoma and pilocytic astrocytoma specimens. Median overall survival of patients with C-erbB-2 negative and C-erbB-2 positive tumors were 30 months (95%CI: 22.5-37.4 months) and 16.9 months (95%CI: 4.3-29.5 months), respectively (p=0.244). Although there was no difference in survival, C-erbB-2 overexpression was observed only in the GBM subtype.

Hsp90 inhibitor 17-AAG reduces ErbB2 levels and inhibits proliferation of the trastuzumab resistant breast tumor cell line JIMT-1.

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Zsebik, Barbara; Citri, Ami; Isola, Jorma; Yarden, Yosef; Szöllosi, János; Vereb, György

2006-04-15

ErbB2, a member of the EGF receptor family of tyrosine kinases is overexpressed on many tumor cells of epithelial origin and is the molecular target of trastuzumab (Herceptin), the first humanized antibody used in the therapy of solid tumors. Trastuzumab, which is thought to act, at least in part, by downregulating ErbB2 expression is only effective in approximately 30-40% of ErbB2 positive breast tumors. Geldanamycin and its derivative 17-AAG are potential antitumor agents capable of downregulating client proteins of Hsp90, including ErbB2. To investigate the ability of 17-AAG to downregulate ErbB2 in trastuzumab resistant breast cancer cells and the possibility of 17-AAG and trastuzumab potentiating each other's effect, the recently established trastuzumab resistant breast cancer cell line, JIMT-1 was compared to the known trastuzumab sensitive SKBR-3 line. Baseline and stimulus-evoked dimerization and activation levels of ErbB2, and the effects of trastuzumab and 17-AAG alone and in combination on cell proliferation and apoptosis, as well as on ErbB2 expression and phosphorylation have been measured. Baseline activation and amenability to activation and downregulation by trastuzumab was much lower in the resistant line. However, 17-AAG enhanced ErbB2 homodimerization after 5-10 min of treatment in both cell lines, and decreased proliferation with an IC50 of 70 nM for SKBR-3 and 10nM for JIMT-1. Thus, 17-AAG may be a useful drug in trastuzumab resistant ErbB2 overexpressing tumors. The antiproliferative effect of 17-AAG was positively correlated with phosphorylation and downregulation of ErbB2 and was dominated by apoptosis, although, especially at higher doses, necrosis was also present. Interestingly, IC50 values for ErbB2 downregulation and phosphorylation, in the 30-40 nM range, were not significantly different for the two cell lines. This observation and the negative correlation between resting ErbB2 levels and the antiproliferative effect of 17-AAG may

Cdk2-Null Mice Are Resistant to ErbB-2-Induced Mammary Tumorigenesis

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Dipankar Ray

2011-05-01

Full Text Available The concept of targeting G1 cyclin-dependent kinases (CDKs in breast cancer treatments is supported by the fact that the genetic ablation of Cdk4 had minimal impacts on normal cell proliferation in majority of cell types, resulting in near-normal mouse development, whereas such loss of Cdk4 completely abrogated ErbB-2/neu-induced mammary tumorigenesis in mice. In most human breast cancer tissues, another G1-regulatory CDK, CDK2, is also hyperactivated by various mechanisms and is believed to be an important therapeutic target. In this report, we provide genetic evidence that CDK2 is essential for proliferation and oncogenesis of murine mammary epithelial cells. We observed that 87% of Cdk2-null mice were protected from ErbB-2-induced mammary tumorigenesis. Mouse embryonic fibroblasts isolated from Cdk2-null mouse showed resistance to various oncogene-induced transformation. Previously, we have reported that hemizygous loss of Cdc25A, the major activator of CDK2, can also protect mice from ErbB-2-induced mammary tumorigenesis [Cancer Res (2007 67(14: 6605–11]. Thus, we propose that CDC25A-CDK2 pathway is critical for the oncogenic action of ErbB-2 in mammary epithelial cells, in a manner similar to Cyclin D1/CDK4 pathway.

Repression of transcription mediated at a thyroid hormone response element by the v-erb-A oncogene product

DEFF Research Database (Denmark)

Sap, J; Muñoz, A; Schmitt, J

1989-01-01

Several recent observations, such as the identification of the cellular homologue of the v-erb-A oncogene as a thyroid-hormone receptor, have strongly implicated nuclear oncogenes in transcriptional control mechanisms. The v-erb-A oncogene blocks the differentiation of erythroid cells, and changes...

Solution structure of the human Grb7-SH2 domain/erbB2 peptide complex and structural basis for Grb7 binding to ErbB2

International Nuclear Information System (INIS)

Ivancic, Monika; Daly, Roger J.; Lyons, Barbara A.

2003-01-01

The solution structure of the hGrb7-SH2 domain in complex with a ten amino acid phosphorylated peptide ligand representative of the erbB2 receptor tyrosine kinase (pY1139) is presented as determined by nuclear magnetic resonance methods. The hGrb7-SH2 domain structure reveals the Src homology 2 domain topology consisting of a central β-sheet capped at each end by an α-helix. The presence of a four residue insertion in the region between β-strand E and the EF loop and resulting influences on the SH2 domain/peptide complex structure are discussed. The binding conformation of the erbB2 peptide is in a β-turn similar to that found in phosphorylated tyrosine peptides bound to the Grb2-SH2 domain. To our knowledge this is only the second example of an SH2 domain binding its naturally occurring ligands in a turn, instead of extended, conformation. Close contacts between residues responsible for binding specificity in hGrb7-SH2 and the erbB2 peptide are characterized and the potential effect of mutation of these residues on the hGrb7-SH2 domain structure is discussed

Stimulation of nuclear receptor REV-ERBs regulates tumor necrosis factor-induced expression of proinflammatory molecules in C6 astroglial cells

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Morioka, Norimitsu, E-mail: mnori@hiroshima-u.ac.jp; Tomori, Mizuki; Zhang, Fang Fang; Saeki, Munenori; Hisaoka-Nakashima, Kazue; Nakata, Yoshihiro

2016-01-08

Under physiological conditions, astrocytes maintain homeostasis in the CNS. Following inflammation and injury to the CNS, however, activated astrocytes produce neurotoxic molecules such as cytokines and chemokines, amplifying the initial molecular-cellular events evoked by inflammation and injury. Nuclear receptors REV-ERBα and REV-ERBβ (REV-ERBs) are crucial in the regulation of inflammation- and metabolism-related gene transcription. The current study sought to elucidate a role of REV-ERBs in rat C6 astroglial cells on the expression of inflammatory molecules following stimulation with the neuroinflammatory cytokine tumor necrosis factor (TNF). Stimulation of C6 cells with TNF (10 ng/ml) significantly increased the mRNA expression of CCL2, interleukin-6 (IL-6), inducible nitric oxide synthase (iNOS), and matrix metalloprotease (MMP)-9, but not fibroblast growth factor-2 (FGF-2), cyclooxygenase-2 (COX-2) and MMP-2. Treatment with either REV-ERB agonists GSK4112 or SR9009 significantly blocked TNF-induced upregulation of CCL2 mRNA and MMP-9 mRNA, but not IL-6 mRNA and iNOS mRNA expression. Furthermore, treatment with RGFP966, a selective histone deacetylase 3 (HDAC3) inhibitor, potently reversed the inhibitory effects of GSK4112 on TNF-induced expression of MMP-9 mRNA, but not CCL2 mRNA. Expression of Rev-erbs mRNA in C6 astroglial cells, primary cultured rat cortical and spinal astrocytes was confirmed by reverse transcription polymerase chain reaction. Together, the findings demonstrate an anti-inflammatory effect, downregulating of MMP-9 and CCL2 transcription, of astroglial REV-ERBs activation through HDAC3-dependent and HDAC3-independent mechanisms. - Highlights: • Rev-erbα mRNA and Rev-erbβ mRNA are expressed in C6 astroglial cells. • TNF increases the expression of CCL2, IL-6, MMP-9 and iNOS mRNA. • REV-ERB activation inhibits CCL2 mRNA and MMP-9 mRNA expression. • HDAC3 activity is involved in the inhibitory effect of REV-ERB on MMP-9 induction.

Stimulation of nuclear receptor REV-ERBs regulates tumor necrosis factor-induced expression of proinflammatory molecules in C6 astroglial cells

International Nuclear Information System (INIS)

Morioka, Norimitsu; Tomori, Mizuki; Zhang, Fang Fang; Saeki, Munenori; Hisaoka-Nakashima, Kazue; Nakata, Yoshihiro

2016-01-01

Under physiological conditions, astrocytes maintain homeostasis in the CNS. Following inflammation and injury to the CNS, however, activated astrocytes produce neurotoxic molecules such as cytokines and chemokines, amplifying the initial molecular-cellular events evoked by inflammation and injury. Nuclear receptors REV-ERBα and REV-ERBβ (REV-ERBs) are crucial in the regulation of inflammation- and metabolism-related gene transcription. The current study sought to elucidate a role of REV-ERBs in rat C6 astroglial cells on the expression of inflammatory molecules following stimulation with the neuroinflammatory cytokine tumor necrosis factor (TNF). Stimulation of C6 cells with TNF (10 ng/ml) significantly increased the mRNA expression of CCL2, interleukin-6 (IL-6), inducible nitric oxide synthase (iNOS), and matrix metalloprotease (MMP)-9, but not fibroblast growth factor-2 (FGF-2), cyclooxygenase-2 (COX-2) and MMP-2. Treatment with either REV-ERB agonists GSK4112 or SR9009 significantly blocked TNF-induced upregulation of CCL2 mRNA and MMP-9 mRNA, but not IL-6 mRNA and iNOS mRNA expression. Furthermore, treatment with RGFP966, a selective histone deacetylase 3 (HDAC3) inhibitor, potently reversed the inhibitory effects of GSK4112 on TNF-induced expression of MMP-9 mRNA, but not CCL2 mRNA. Expression of Rev-erbs mRNA in C6 astroglial cells, primary cultured rat cortical and spinal astrocytes was confirmed by reverse transcription polymerase chain reaction. Together, the findings demonstrate an anti-inflammatory effect, downregulating of MMP-9 and CCL2 transcription, of astroglial REV-ERBs activation through HDAC3-dependent and HDAC3-independent mechanisms. - Highlights: • Rev-erbα mRNA and Rev-erbβ mRNA are expressed in C6 astroglial cells. • TNF increases the expression of CCL2, IL-6, MMP-9 and iNOS mRNA. • REV-ERB activation inhibits CCL2 mRNA and MMP-9 mRNA expression. • HDAC3 activity is involved in the inhibitory effect of REV-ERB on MMP-9 induction.

REV-ERB-ALPHA circadian gene variant associates with obesity in two independent populations: Mediterranean and North American.

Science.gov (United States)

Garaulet, Marta; Smith, Caren E; Gomez-Abellán, Purificación; Ordovás-Montañés, María; Lee, Yu-Chi; Parnell, Laurence D; Arnett, Donna K; Ordovás, José M

2014-04-01

Despite the solid connection between REV-ERB and obesity, the information about whether genetic variations at this locus may be associated with obesity traits is scarce. Therefore our objective was to study the association between REV-ERB-ALPHA1 rs2314339 and obesity in two independent populations. Participants were 2214 subjects from Spanish Mediterranean (n = 1404) and North American (n = 810) populations. Anthropometric, biochemical, dietary, and genotype analyses were performed. We found novel associations between the REV-ERB-ALPHA1 rs2314339 genotype and obesity in two independent populations: in Spanish Mediterranean and North American groups, the frequency of the minor-allele-carriers (AA+ AG) was significantly lower in the "abdominally obese" group than in those of the "nonabdominally obese" group (p obesity than noncarriers, and the effect was of similar magnitude for both populations (OR ≈ 1.50). There were consistent associations between REV-ERB-ALPHA1 genotype and obesity-related traits (p obesity was also detected in the Mediterranean population. This new discovery highlights the importance of REV-ERB-ALPHA1 in obesity and provides evidence for the connection between our biological clock and obesity-related traits. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Ablating ErbB4 in PV neurons attenuates synaptic and cognitive deficits in an animal model of Alzheimer's disease.

Science.gov (United States)

Zhang, Heng; Zhang, Ling; Zhou, Dongming; He, Xiao; Wang, Dongpi; Pan, Hongyu; Zhang, Xiaoqin; Mei, Yufei; Qian, Qi; Zheng, Tingting; Jones, Frank E; Sun, Binggui

2017-10-01

Accumulation of amyloid β (Aβ) induces neuronal, synaptic, and cognitive deficits in patients and animal models of Alzheimer's disease (AD). The underlying mechanisms, however, remain to be fully elucidated. In the present study, we found that Aβ interacted with ErbB4, a member of the receptor tyrosine kinase family and mainly expressed in GABAergic interneurons. Deleting ErbB4 in parvalbumin-expressing neurons (PV neurons) significantly attenuated oligomeric Aβ-induced suppression of long term potentiation (LTP). Furthermore, specific ablation of ErbB4 in PV neurons via Cre/loxP system greatly improved spatial memory and synaptic plasticity in the hippocampus of hAPP-J20 mice. The deposition of Aβ detected by 3D6 and Thioflavin S staining and the proteolytic processing of hAPP analyzed by western blotting were not affected in the hippocampus of hAPP-J20 mice by deleting ErbB4 in PV neurons. Our data suggested that ErbB4 in PV neurons mediated Aβ-induced synaptic and cognitive dysfunctions without affecting Aβ levels. Copyright © 2017 Elsevier Inc. All rights reserved.

ErbB1-4-dependent EGF/neuregulin signals and their cross talk in the central nervous system: pathological implications in schizophrenia and Parkinson’s disease

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Yuriko eIwakura

2013-02-01

Full Text Available Ligands for ErbB1-4 receptor tyrosine kinases, such as epidermal growth factor (EGF and neuregulins, regulate brain development and function. Thus, abnormalities in their signaling are implicated in the etiology or pathology of schizophrenia and Parkinson’s disease. Among the ErbB receptors, ErbB1 and ErbB4 are expressed in dopamine and GABA neurons, while ErbB1, 2, and/or 3 are mainly present in oligodendrocytes, astrocytes and their precursors. Thus, deficits in ErbB signaling might contribute to schizophrenia neuropathology stemming from these cell types. By incorporating the latest cancer molecular biology as well as our recent progress, we discuss signal cross talk between the ErbB1-4 subunits and their neurobiological functions in each cell type. The potential contribution of virus-derived cytokines (virokines that mimic EGF and neuregulin-1 in brain diseases are also discussed.

Activation of ErbB3, EGFR and Erk is essential for growth of human breast cancer cell lines with acquired resistance to fulvestrant

DEFF Research Database (Denmark)

Frogne, Thomas; Benjaminsen, Rikke; Sonne-Hansen, Katrine

2008-01-01

cell lines concomitant with inhibition of Erk and unaltered Akt activation. In concert, inhibition of Erk with U0126 preferentially reduced growth of resistant cell lines. Treatment with ErbB3 neutralizing antibodies inhibited ErbB3 activation and resulted in a modest but statistically significant...... activation was observed only in the parental MCF-7 cells. The downstream kinases pAkt and pErk were increased in five of seven and in all seven resistant cell lines, respectively. Treatment with the EGFR inhibitor gefitinib preferentially inhibited growth and reduced the S phase fraction in the resistant...... growth inhibition of two resistant cell lines. These data indicate that ligand activated ErbB3 and EGFR, and Erk signaling play important roles in fulvestrant resistant cell growth. Furthermore, the decreased level of ErbB4 in resistant cells may facilitate heterodimerization of ErbB3 with EGFR and ErbB2...

Positive expression of p53, c-erbB2 and MRP proteins is correlated with survival rates of NSCLC patients.

Science.gov (United States)

Xu, Yujin; Wang, Liancong; Zheng, Xiao; Liu, Guan; Wang, Yuezhen; Lai, Xiaojing; Li, Jianqiang

2013-05-01

The incidence of lung cancer is one of the leading causes of mortality. This study aimed to investigate the prognostic and predictive importance of p53, c-erbB2 and multidrug resistance proteins (MRP) expression and its correlation with clinicopathological characteristics of patients with non-small cell lung cancer (NSCLC). Expression of p53, c-erbB2 and MRP proteins in 152 tumor samples from resected primary NSCLCs was detected by immunohistochemical staining. The correlation of proteins, survival and clinicopathological characteristics was investigated in 152 patients undergoing potentially curative surgery. The positive rates of p53, c-erbB2 and MRP expression were 53.9 (82/152), 44.1 (67/152) and 43.4% (66/152), respectively. Overall survival rates of patients were markedly correlated with the overexpression of p53, c-erbB2 and MRP proteins. One, 2- and 3-year survival rates of patients exhibiting a positive expression of these proteins were 72.6, 54.8 and 32.2%, respectively. These rates were lower compared with those of patients with a negative expression of these proteins (92.1, 78.5 and 63.4%) (P=0.02, 0.01 or 0.00, respectively). Results of Cox's regression analysis showed that c-erbB2 expression and cell differentiation were independent prognostic factors in patients with NSCLC. These findings suggest that the positive expression of p53, c-erbB2 and MRP proteins is correlated with the survival rates of NSCLC patients. Detection of positive p53, c-erbB2 and MRP expression may be a useful predictive indicator of prognosis. Positive c-erbB2 expression is an independent prognostic factor, with a potential to be used as a predictive indicator of chemotherapy efficacy in NSCLC patients.

The ectodomain of cadherin-11 binds to erbB2 and stimulates Akt phosphorylation to promote cranial neural crest cell migration.

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Ketan Mathavan

Full Text Available During development, a multi-potent group of cells known as the cranial neural crest (CNC migrate to form craniofacial structures. Proper migration of these cells requires proteolysis of cell adhesion molecules, such as cadherins. In Xenopus laevis, preventing extracellular cleavage of cadherin-11 impairs CNC migration. However, overexpression of the soluble cleavage product (EC1-3 is capable of rescuing this phenotype. The mechanism by which EC1-3 promotes CNC migration has not been investigated until now. Here we show that EC1-3 stimulates phosphorylation of Akt, a target of PI3K, in X.laevis CNC. Through immunoprecipitation experiments, we determined that EC1-3 interacts with all ErbB receptors, PDGFRα, and FGFR1. Of these receptors, only ErbB2 was able to produce an increase in Akt phosphorylation upon treatment with a recombinant EC1-3. This increase was abrogated by mubritinib, an inhibitor of ErbB2. We were able to recapitulate this decrease in Akt phosphorylation in vivo by knocking down ErbB2 in CNC cells. Knockdown of the receptor also significantly reduced CNC migration in vivo. We confirmed the importance of ErbB2 and ErbB receptor signaling in CNC migration using mubritinib and canertinib, respectively. Mubritinib and the PI3K inhibitor LY294002 significantly decreased cell migration while canertinib nearly prevented it altogether. These data show that ErbB2 and Akt are important for CNC migration and implicate other ErbB receptors and Akt-independent signaling pathways. Our findings provide the first example of a functional interaction between the extracellular domain of a type II classical cadherin and growth factor receptors.

Small tyrosine kinase inhibitors interrupt EGFR signaling by interacting with erbB3 and erbB4 in glioblastoma cell lines

Energy Technology Data Exchange (ETDEWEB)

Carrasco-Garcia, Estefania; Saceda, Miguel [Instituto de Biologia Molecular y Celular, Universidad Miguel Hernandez, 03202 Elche (Alicante) (Spain); Unidad de Investigacion, Hospital General Universitario de Elche, 03203 Elche (Alicante) (Spain); Grasso, Silvina; Rocamora-Reverte, Lourdes; Conde, Mariano; Gomez-Martinez, Angeles [Instituto de Biologia Molecular y Celular, Universidad Miguel Hernandez, 03202 Elche (Alicante) (Spain); Garcia-Morales, Pilar [Instituto de Biologia Molecular y Celular, Universidad Miguel Hernandez, 03202 Elche (Alicante) (Spain); Unidad de Investigacion, Hospital General Universitario de Elche, 03203 Elche (Alicante) (Spain); Ferragut, Jose A. [Instituto de Biologia Molecular y Celular, Universidad Miguel Hernandez, 03202 Elche (Alicante) (Spain); Martinez-Lacaci, Isabel, E-mail: imlacaci@umh.es [Instituto de Biologia Molecular y Celular, Universidad Miguel Hernandez, 03202 Elche (Alicante) (Spain); Unidad AECC de Investigacion Traslacional en Cancer, Hospital Universitario Virgen de la Arrixaca, 30120 Murcia (Spain)

2011-06-10

Signaling through the epidermal growth factor receptor (EGFR) is relevant in glioblastoma. We have determined the effects of the EGFR inhibitor AG1478 in glioblastoma cell lines and found that U87 and LN-229 cells were very sensitive to this drug, since their proliferation diminished and underwent a marked G{sub 1} arrest. T98 cells were a little more refractory to growth inhibition and A172 cells did not undergo a G{sub 1} arrest. This G{sub 1} arrest was associated with up-regulation of p27{sup kip1}, whose protein turnover was stabilized. EGFR autophosphorylation was blocked with AG1478 to the same extent in all the cell lines. Other small-molecule EGFR tyrosine kinase inhibitors employed in the clinic, such as gefitinib, erlotinib and lapatinib, were able to abrogate proliferation of glioblastoma cell lines, which underwent a G{sub 1} arrest. However, the EGFR monoclonal antibody, cetuximab had no effect on cell proliferation and consistently, had no effect on cell cycle either. Similarly, cetuximab did not inhibit proliferation of U87 {Delta}EGFR cells or primary glioblastoma cell cultures, whereas small-molecule EGFR inhibitors did. Activity of downstream signaling molecules of EGFR such as Akt and especially ERK1/2 was interrupted with EGFR tyrosine kinase inhibitors, whereas cetuximab treatment could not sustain this blockade over time. Small-molecule EGFR inhibitors were able to prevent phosphorylation of erbB3 and erbB4, whereas cetuximab only hindered EGFR phosphorylation, suggesting that EGFR tyrosine kinase inhibitors may mediate their anti-proliferative effects through other erbB family members. We can conclude that small-molecule EGFR inhibitors may be a therapeutic approach for the treatment of glioblastoma patients.

The presence of c-erbB-2 gene product-related protein in culture medium conditioned by breast cancer cell line SK-BR-3

International Nuclear Information System (INIS)

Alper, O.; Yamaguchi, K.; Hitomi, J.; Honda, S.; Matsushima, T.; Abe, K.

1990-01-01

The Mr 185,000 glycoprotein encoded by human c-erbB-2/neu/HER2 gene, termed c-erbB-2 gene product, shows a close structural similarity with epidermal growth factor receptor and is now regarded to be a growth factor receptor for an as yet unidentified ligand. Abundant c-erbB-2 mRNA was demonstrated by Northern blot studies in the human breast cancer cell line SK-BR-3. Cellular radiolabeling experiments followed by immunoprecipitation with three different anti-c-erbB-2 gene product antibodies, recognizing extracellular domain, kinase domain, and carboxyl-terminal portion, respectively, demonstrated the production of a large amount of c-erbB-2 gene product which had the capacity to be phosphorylated. Immunization of mice with concentrated culture medium conditioned by SK-BR-3 cells always generated antibodies against c-erbB-2 gene product, demonstrating that this culture medium contained substance(s) immunologically indistinguishable from c-erbB-2 gene product. This observation was supported by the successful development of a monoclonal antibody against c-erbB-2 gene product, GFD-OA-p185-1, by immunizing mice with this culture medium. The biochemical nature of the substance(s) present in the culture medium was further characterized. When the culture medium conditioned by [35S]cysteine-labeled SK-BR-3 cells was immunoprecipitated by three different anti-c-erbB-2 gene product antibodies, only the antibody recognizing extracellular domain precipitated the [35S]-labeled protein with a molecular weight of 110,000, namely p110. The newly developed monoclonal antibody also immunoprecipitated this protein

Detection of erbB2 copy number variations in plasma of patients with esophageal carcinoma

International Nuclear Information System (INIS)

Andolfo, Immacolata; Orditura, Michele; Ciardiello, Fortunato; De Vita, Fernando; Zollo, Massimo; Petrosino, Giuseppe; Vecchione, Loredana; De Antonellis, Pasqualino; Capasso, Mario; Montanaro, Donatella; Gemei, Marica; Troncone, Giancarlo; Iolascon, Achille

2011-01-01

Mortality is high in patients with esophageal carcinoma as tumors are rarely detected before the disease has progressed to an advanced stage. Here, we sought to isolate cell-free DNA released into the plasma of patients with esophageal carcinoma, to analyze copy number variations of marker genes in the search for early detection of tumor progression. Plasma of 41 patients with esophageal carcinoma was prospectively collected before tumor resection and chemotherapy. Our dataset resulted heterogeneous for clinical data, resembling the characteristics of the tumor. DNA from the plasma was extracted to analyze copy number variations of the erbB2 gene using real-time PCR assays. The real-time PCR assays for erbB2 gene showed significant (P = 0.001) copy number variations in the plasma of patients with esophageal carcinoma, as compared to healthy controls with high sensitivity (80%) and specificity (95%). These variations in erbB2 were negatively correlated to the progression free survival of these patients (P = 0.03), and revealed a further risk category stratification of patients with low VEGF expression levels. The copy number variation of erbB2 gene from plasma can be used as prognostic marker for early detection of patients at risk of worse clinical outcome in esophageal cancer

NOAA-9 Earth Radiation Budget Experiment (ERBE) scanner offsets determination

Science.gov (United States)

Avis, Lee M.; Paden, Jack; Lee, Robert B., III; Pandey, Dhirendra K.; Stassi, Joseph C.; Wilson, Robert S.; Tolson, Carol J.; Bolden, William C.

1994-01-01

The Earth Radiation Budget Experiment (ERBE) instruments are designed to measure the components of the radiative exchange between the Sun, Earth and space. ERBE is comprised of three spacecraft, each carrying a nearly identical set of radiometers: a three-channel narrow-field-of-view scanner, a two-channel wide-field-of-view (limb-to-limb) non-scanning radiometer, a two-channel medium field-of view (1000 km) non-scanning radiometer, and a solar monitor. Ground testing showed the scanners to be susceptible to self-generated and externally generated electromagnetic noise. This paper describes the pre-launch corrective measures taken and the post-launch corrections to the NOAA-9 scanner data. The NOAA-9 scanner has met the mission objectives in accuracy and precision, in part because of the pre-launch reductions of and post-launch data corrections for the electromagnetic noise.

Análise da expressão imuno-histoquímica de c-erbB-2 e EGFR em carcinoma epidermóide de esôfago Immunohistochemical expression of c-erbB-2 and EGFR in esophageal squamous cell carcinoma

Directory of Open Access Journals (Sweden)

Yukie Sato

2007-08-01

Full Text Available INTRODUÇÃO: O carcinoma epidermóide de esôfago (CEE possui alta incidência em nosso país, com altas taxas de mortalidade. A família dos receptores do fator epitelial de crescimento (EGFR é composta por quatro membros, e muitos estudos têm sido direcionados para a expressão de EGFR e c-erbB-2, com implicações terapêuticas. OBJETIVO: Investigar as expressões imuno-histoquímicas de EGFR e c-erbB-2 e correlacioná-las a aspectos clinicopatológicos em casos de CEE. MATERIAL E MÉTODOS: Para esse estudo, dados clinicopatológicos de 613 CEE foram revistos. A imunoistoquímica foi feita utilizando anticorpo policlonal para c-erbB-2 e monoclonal para EGFR em 597 e 585 casos, respectivamente. Os casos representados por peças cirúrgicas foram distribuídos em três blocos de parafina de tissue microarray (TMA, inseridos em duplicata; aqueles com biópsias foram analisados em corte convencional. Todos foram classificados de acordo com intensidade e padrão de marcação de membrana das células tumorais. RESULTADOS: As expressões de c-erbB-2 e EGFR foram observadas em 42,4% e 77,6% dos casos, respectivamente. Observou-se correlação estatisticamente significativa entre as expressões de c-erbB-2 (p = 0,04 e EGFR (p = 0,01 e grau histológico. Ambos os marcadores foram significativamente mais expressos em casos bem/moderadamente diferenciados do que nos pouco diferenciados/indiferenciados. Embora não tenha sido significativa, houve uma tendência de associação entre superexpressão de c-erbB-2 e sítio do tumor, em que casos positivos ocorreram com mais freqüência no terço médio do esôfago. Nenhuma correlação significativa foi verificada entre essas proteínas e sobrevida global. CONCLUSÃO: Os resultados podem sugerir um papel primordial para essas proteínas na diferenciação tumoral em CEE.INTRODUCTION: Esophageal squamous cell carcinoma (ESCC is highly prevalent in Brazil, and responsible for high mortality index. The

TOA Radiation Balance Study through Reprocessed ERBS WFOV Nonscanner data from 1985 to 1998

Science.gov (United States)

Shrestha, A. K.; Kato, S.; Wong, T.; Stackhouse, P. W., Jr.; Doelling, D. R.; Loughman, R. P.

2017-12-01

Wide-field-of-view (WFOV) nonscanner instrument onboard Earth Radiation Budget Satellite (ERBS) provided broadband irradiances at the top-of-atmosphere (TOA) from 1985 to 1999. However, earlier studies show that the uncertainty in this TOA radiation dataset is significantly higher during the period after the Mt. Pinatubo eruption and battery issue in 1991. In addition, the difference between daytime and nighttime longwave irradiance drifts with time throughout the lifetime of the instrument. We re-processed ERBS WFOV data using the algorithm similar to the one used in the CERES project and calibrated it with CERES-derived irradiances. In addition, the spatial coverage of ERBS irradiances is extended to global from near-global (60°N to 60°S latitudes) using CERES climatological ratio of the near-global to global mean irradiances. The near-global standard deviation of deseasonalized shortwave anomalies computed with Ed4 decreases to 3.2 Wm-2 from 8.0 Wm-2, computed with previous version. In addition, the drift of day-minus-night longwave irradiance is reduced by one third. Similar to the previous version, however, the Ed4 global shortwave irradiance averaged over the 1994 to 1997 period (second period) is smaller by 2.2 Wm-2 compared to that averaged over the 1985 to 1989 period (first period). In addition, the global longwave irradiance in the second period is larger by 0.7 Wm-2 compared to that averaged over the first period. When the difference of two periods is computed (second period minus first period) with the DEEP-C data product (Allan et al. 2014), the difference is 0.5 (-0.3) Wm-2 for shortwave (longwave). The global net imbalance at the TOA computed with ERBS and DEEP-C data sets are, respectively, 0.45 (1.89) Wm-2 and 0.17 (0.96) Wm-2 for the first (second) period. The net imbalance for the CERES period in the 2000s is 0.65 Wm-2. In this presentation, we will further compare Ed4 ERBS-derived TOA net imbalance with ocean heating rates. Re-processed ERBS

The potential for collocated AGLP and ERBE data for fire, smoke, and radiation budget studies

International Nuclear Information System (INIS)

Christopher, S.A.; Chou, J.

1997-01-01

One month of the Advanced Very High Resolution Radiometer (AVHRR) Global Area Coverage (GAC) Land Pathfinder (AGLP) data from September 1985 are used to examine the spatial and temporal distribution of fires over four major ecosystems in South America. The Earth Radiation Budget Experiment (ERBE) scanner data are used to examine the top of atmosphere (TOA) shortwave and longwave fluxes over smoke generated from biomass burn- ing. The relationship between the AGLP-derived Normalized Difference Vegetation Index (NDVI) and the ERBE-estimated clear sky albedos are also examined as a function of the four ecosystems. This study shows that the grassland areas in South America have the highest number of fires for September 1985, and their corresponding NDVI values are smaller than the tropical rainforest region where the number of fires were comparatively small. Clear sky statistics accumulated during the days when smoke was not present show that clear sky albedos derived from ERBE are higher for grassland areas when compared to the tropical rainforest. The results show that the AGLP can be used to determine the spatial and temporal distribution of fires along with vegetation characteristics, while ERBE data can provide necessary information on broadband albedos and regional top of atmosphere radiative impacts of biomass burning aerosols. Since the AGLP data are available from 1981 to the present day, several climate-related issues can be addressed

A pathological study on overexpression of c-erbB-2, EGFR proteins in human radiation skin ulcer

International Nuclear Information System (INIS)

Zhao Po; Yang Zhixiang; Wang Dewen; Li Guomin; Gao Yabin

1996-01-01

We performed an immunohistochemical study in 25 cases of human radiation skin ulcer by using c-erbB-2, Epidermal growth factor receptor (EGFR), protein antibodies and repairing method of antigen with microwave oven. The results show that the positive rate for overexpression of c-erbB-2 oncoprotein was 92.0% (23/25), and EGFR was 73.7%(14/19). The positive position for overexpression of c-crbB-2 was mainly observed on cell membrane of squamous epithelial cells and cell plasma of fibroblasts, endotheliocytes, and leiomyocytes in media and fibrocytes in adventitia of the arterioles in mesenchyme. It is suggested that the overexpression of c-erbB-2 and EGFR proteins might be related to cancer transformation and poor healing in radiation skin ulcers

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

DEFF Research Database (Denmark)

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

2015-01-01

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

Effect of acute acid-base disturbances on ErbB1/2 tyrosine phosphorylation in rabbit renal proximal tubules.

Science.gov (United States)

Skelton, Lara A; Boron, Walter F

2013-12-15

The renal proximal tubule (PT) is a major site for maintaining whole body pH homeostasis and is responsible for reabsorbing ∼80% of filtered HCO3(-), the major plasma buffer, into the blood. The PT adapts its rate of HCO3(-) reabsorption (JHCO3(-)) in response to acute acid-base disturbances. Our laboratory previously showed that single isolated perfused PTs adapt JHCO3(-) in response to isolated changes in basolateral (i.e., blood side) CO2 and HCO3(-) concentrations but, surprisingly, not to pH. The response to CO2 concentration can be blocked by the ErbB family tyrosine kinase inhibitor PD-168393. In the present study, we exposed enriched rabbit PT suspensions to five acute acid-base disturbances for 5 and 20 min using a panel of phosphotyrosine (pY)-specific antibodies to determine the influence of each disturbance on pan-pY, ErbB1-specific pY (four sites), and ErbB2-specific pY (two sites). We found that each acid-base treatment generated a distinct temporal pY pattern. For example, the summated responses of the individual ErbB1/2-pY sites to each disturbance showed that metabolic acidosis (normal CO2 concentration and reduced HCO3(-) concentration) produced a transient summated pY decrease (5 vs. 20 min), whereas metabolic alkalosis produced a transient increase. Respiratory acidosis (normal HCO3(-) concentration and elevated CO2 concentration) had little effect on summated pY at 5 min but produced an elevation at 20 min, whereas respiratory alkalosis produced a reduction at 20 min. Our data show that ErbB1 and ErbB2 in the PT respond to acute acid-base disturbances, consistent with the hypothesis that they are part of the signaling cascade.

Altered Sleep Homeostasis in Rev-erbα Knockout Mice.

Science.gov (United States)

Mang, Géraldine M; La Spada, Francesco; Emmenegger, Yann; Chappuis, Sylvie; Ripperger, Jürgen A; Albrecht, Urs; Franken, Paul

2016-03-01

The nuclear receptor REV-ERBα is a potent, constitutive transcriptional repressor critical for the regulation of key circadian and metabolic genes. Recently, REV-ERBα's involvement in learning, neurogenesis, mood, and dopamine turnover was demonstrated suggesting a specific role in central nervous system functioning. We have previously shown that the brain expression of several core clock genes, including Rev-erbα, is modulated by sleep loss. We here test the consequences of a loss of REV-ERBα on the homeostatic regulation of sleep. EEG/EMG signals were recorded in Rev-erbα knockout (KO) mice and their wild type (WT) littermates during baseline, sleep deprivation, and recovery. Cortical gene expression measurements after sleep deprivation were contrasted to baseline. Although baseline sleep/wake duration was remarkably similar, KO mice showed an advance of the sleep/wake distribution relative to the light-dark cycle. After sleep onset in baseline and after sleep deprivation, both EEG delta power (1-4 Hz) and sleep consolidation were reduced in KO mice indicating a slower increase of homeostatic sleep need during wakefulness. This slower increase might relate to the smaller increase in theta and gamma power observed in the waking EEG prior to sleep onset under both conditions. Indeed, the increased theta activity during wakefulness predicted delta power in subsequent NREM sleep. Lack of Rev-erbα increased Bmal1, Npas2, Clock, and Fabp7 expression, confirming the direct regulation of these genes by REV-ERBα also in the brain. Our results add further proof to the notion that clock genes are involved in sleep homeostasis. Because accumulating evidence directly links REV-ERBα to dopamine signaling the altered homeostatic regulation of sleep reported here are discussed in that context. © 2016 Associated Professional Sleep Societies, LLC.

A Novel Pathway to Down-Regulate ErbB Signaling in Mammary Epithelial

National Research Council Canada - National Science Library

Duan, Lei

2001-01-01

.... Based on these observations, this proposal is investigating the role of Cbl-mediated ubiquitination as a signal for targeting activated ErbB receptors to lysosomes where they undergo degradation...

ErbB2 Pathway Activation upon Smad4 Loss Promotes Lung Tumor Growth and Metastasis

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Jian Liu

2015-03-01

Full Text Available Lung cancer remains the leading cause of cancer death. Genome sequencing of lung tumors from patients with squamous cell carcinoma has identified SMAD4 to be frequently mutated. Here, we use a mouse model to determine the molecular mechanisms by which Smad4 loss leads to lung cancer progression. Mice with ablation of Pten and Smad4 in airway epithelium develop metastatic adenosquamous tumors. Comparative transcriptomic and in vivo cistromic analyses determine that loss of PTEN and SMAD4 results in ELF3 and ErbB2 pathway activation due to decreased expression of ERRFI1, a negative regulator of ERBB2 in mouse and human cells. The combinatorial inhibition of ErbB2 and Akt signaling attenuate tumor progression and cell invasion, respectively. Expression profile analysis of human lung tumors substantiated the importance of the ErbB2/Akt/ELF3 signaling pathway as both a prognostic biomarker and a therapeutic drug target for treating lung cancer.

Prognostic impact of p53, c-erbB-2 and epidermal growth factor receptor on head and neck carcinoma

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Orlando Parise Junior

Full Text Available CONTEXT: p53, c-erbB-2 and epidermal growth factor receptor (EGFR are cancer-related proteins that are usually expressed in head and neck squamous cell carcinoma (SCC. Their prognostic value remains controversial. OBJECTIVE: To evaluate the prognostic impact of p53, c-erbB-2 and EGFR expression in head and neck SCC. TYPE OF STUDY: Prospective. SETTING: Head and Neck Surgery Department, Hospital AC Camargo, São Paulo. METHODS: Fifty-four patients were studied for p53, c-erbB-2 and EGFR expression in head and neck SCC and adjacent mucosa, via immunohistochemistry. These data were correlated with histoclinical data and survival. RESULTS: There was a direct association of p53 expression in SCC and mucosa (p = 0.001; loss of c-erbB-2 expression (- from normal mucosa to SCC (p = 0.04; lower frequency of association of c-erbB-2 (+ with EGFR (- in SCC (p = 0.02; and a direct association of EGFR (+ expression in SCC and mitotic index (p = 0.03. The 60-month actuarial survival rates for patients presenting lymph node metastasis were higher when there was no capsule rupture by SCC (48.3%; p = 0.02, no more than one positive lymph node (52.3%; p = 0.004 or clear surgical margins (47.0%; p = 0.01, in comparison with patients presenting capsule rupture (20.2%, two or more positive lymph nodes (18.7% or compromised surgical margins (0.0%, respectively. Patients presenting SCC p53 (+ and EGFR (- demonstrated greater survival (75.0%; p = 0.03 than for the remaining group (33.1%. Multivariate analysis confirmed the positive impact of p53 (+ and EGFR (- on survival (p = 0.02. DISCUSSION: Associations were found for p53, c-erbB-2 and EGFR expression with histoclinical data and prognosis. Interestingly, these results suggest that loss of mucosal c-erbB-2 expression could be involved in SCC carcinogenesis; EGFR expression in SCC is related to tumor mitotic index; and presence of p53 with absence of EGFR expression in head and neck SCC may be a prognostic factor for

Hyaluronan-induced masking of ErbB2 and CD44-enhanced trastuzumab internalisation in trastuzumab resistant breast cancer.

Science.gov (United States)

Pályi-Krekk, Zsuzsanna; Barok, Márk; Isola, Jorma; Tammi, Markku; Szöllosi, János; Nagy, Peter

2007-11-01

Although trastuzumab, a recombinant humanised anti-ErbB2 antibody, is widely used in the treatment of breast cancer, neither its mechanism of action, nor the factors leading to resistance are fully understood. We have previously shown that antibody-dependent cellular cytotoxicity is pivotal in the in vivo effect of trastuzumab against JIMT-1, a cell line showing in vitro resistance to the antibody, and suggested that masking of the trastuzumab-binding epitope by MUC-4, a cell surface mucin, took place. Here, we further explored the role of masking of ErbB2 in connection with CD44 expression and synthesis of its ligand, hyaluronan. We show that high expression of CD44 observed in JIMT-1 cells correlates with ErbB2 downregulation in vivo, while siRNA-mediated inhibition of CD44 expression leads to decreased rate of trastuzumab internalisation and low cell proliferation in vitro. An inhibitor of hyaluronan synthesis, 4-methylumbelliferon (4-MU) significantly reduced the hyaluronan level of JIMT-1 cells both in vivo and in vitro leading to enhanced binding of trastuzumab to ErbB2 and increased ErbB2 down-regulation. Furthermore, the inhibitory effect of trastuzumab on the growth of JIMT-1 xenografts was significantly increased by 4-MU treatment. Our results point to the importance of the CD44-hyaluronan pathway in the escape of tumour cells from receptor-oriented therapy.

Dicty_cDB: Contig-U12531-1 [Dicty_cDB

Lifescience Database Archive (English)

Full Text Available SHGC-CLJ Gasterosteus aculeatus ... 48 0.77 1 ( EY497720 ) CBBP3718.rev CBBP Hirudo medicinalis hermaphrodi...t... 48 0.77 1 ( EY496316 ) CBBP2847.fwd CBBP Hirudo medicinalis hermaphrodit... 48 0.77 1 ( EY496315 ) CBBP2847.rev CBBP Hirudo medi...cinalis hermaphrodit... 48 0.77 1 ( EY484422 ) CBBP13571.fwd CBBP Hirudo medicina...lis hermaphrodi... 48 0.77 1 ( EY484421 ) CBBP13571.rev CBBP Hirudo medicinalis her...maphrodi... 48 0.77 1 ( EY483641 ) CBBP13100.fwd CBBP Hirudo medicinalis hermaphrodi... 48 0.77 1 ( EY483640

Clouds and the Earth's Radiant Energy System (CERES) algorithm theoretical basis document. volume 2; Geolocation, calibration, and ERBE-like analyses (subsystems 1-3)

Science.gov (United States)

Wielicki, B. A. (Principal Investigator); Barkstrom, B. R. (Principal Investigator); Charlock, T. P.; Baum, B. A.; Green, R. N.; Minnis, P.; Smith, G. L.; Coakley, J. A.; Randall, D. R.; Lee, R. B., III

1995-01-01

The theoretical bases for the Release 1 algorithms that will be used to process satellite data for investigation of the Clouds and Earth's Radiant Energy System (CERES) are described. The architecture for software implementation of the methodologies is outlined. Volume 2 details the techniques used to geolocate and calibrate the CERES scanning radiometer measurements of shortwave and longwave radiance to invert the radiances to top-of-the-atmosphere (TOA) and surface fluxes following the Earth Radiation Budget Experiment (ERBE) approach, and to average the fluxes over various time and spatial scales to produce an ERBE-like product. Spacecraft ephemeris and sensor telemetry are used with calibration coefficients to produce a chronologically ordered data product called bidirectional scan (BDS) radiances. A spatially organized instrument Earth scan product is developed for the cloud-processing subsystem. The ERBE-like inversion subsystem converts BDS radiances to unfiltered instantaneous TOA and surface fluxes. The TOA fluxes are determined by using established ERBE techniques. Hourly TOA fluxes are computed from the instantaneous values by using ERBE methods. Hourly surface fluxes are estimated from TOA fluxes by using simple parameterizations based on recent research. The averaging process produces daily, monthly-hourly, and monthly means of TOA and surface fluxes at various scales. This product provides a continuation of the ERBE record.

Das Erbe der Menschheit.

OpenAIRE

Joana Breidenbach; Pál Nyíri

2005-01-01

Le concept d’« héritage » est apparu avec les efforts des États-nations occidentaux modernes émergents, au 19 e siècle, pour apporter une signification nationale à leurs paysages et à leurs environnements construits. Aujourd’hui, cependant, certains des moteurs centraux de ce mouvement de l’héritage sont des acteurs globaux plutôt que nationaux. Le projet le plus prestigieux pour la promotion de l’idée d’« héritage global » est la liste de l’Héritage mondial de l’ Unesco . Que deviennent les ...

Auditory ERB like admissible wavelet packet features for TIMIT phoneme recognition

Directory of Open Access Journals (Sweden)

P.K. Sahu

2014-09-01

Full Text Available In recent years wavelet transform has been found to be an effective tool for time–frequency analysis. Wavelet transform has been used as feature extraction in speech recognition applications and it has proved to be an effective technique for unvoiced phoneme classification. In this paper a new filter structure using admissible wavelet packet is analyzed for English phoneme recognition. These filters have the benefit of having frequency bands spacing similar to the auditory Equivalent Rectangular Bandwidth (ERB scale. Central frequencies of ERB scale are equally distributed along the frequency response of human cochlea. A new sets of features are derived using wavelet packet transform's multi-resolution capabilities and found to be better than conventional features for unvoiced phoneme problems. Some of the noises from NOISEX-92 database has been used for preparing the artificial noisy database to test the robustness of wavelet based features.

Neuregulin-1/erbB-activation improves cardiac function and survival in models of ischemic, dilated, and viral cardiomyopathy.

Science.gov (United States)

Liu, Xifu; Gu, Xinhua; Li, Zhaoming; Li, Xinyan; Li, Hui; Chang, Jianjie; Chen, Ping; Jin, Jing; Xi, Bing; Chen, Denghong; Lai, Donna; Graham, Robert M; Zhou, Mingdong

2006-10-03

We evaluated the therapeutic potential of a recombinant 61-residue neuregulin-1 (beta2a isoform) receptor-active peptide (rhNRG-1) in multiple animal models of heart disease. Activation of the erbB family of receptor tyrosine kinases by rhNRG-1 could provide a treatment option for heart failure, because neuregulin-stimulated erbB2/erbB4 heterodimerization is not only critical for myocardium formation in early heart development but prevents severe dysfunction of the adult heart and premature death. Disabled erbB-signaling is also implicated in the transition from compensatory hypertrophy to failure, whereas erbB receptor-activation promotes myocardial cell growth and survival and protects against anthracycline-induced cardiomyopathy. rhNRG-1 was administered IV to animal models of ischemic, dilated, and viral cardiomyopathy, and cardiac function and survival were evaluated. Short-term intravenous administration of rhNRG-1 to normal dogs and rats did not alter hemodynamics or cardiac contractility. In contrast, rhNRG-1 improved cardiac performance, attenuated pathological changes, and prolonged survival in rodent models of ischemic, dilated, and viral cardiomyopathy, with the survival benefits in the ischemic model being additive to those of angiotensin-converting enzyme inhibitor therapy. In addition, despite continued pacing, rhNRG-1 produced global improvements in cardiac function in a canine model of pacing-induced heart failure. These beneficial effects make rhNRG-1 promising as a broad-spectrum therapeutic for the treatment of heart failure due to a variety of common cardiac diseases.

Dicty_cDB: Contig-U11651-1 [Dicty_cDB

Lifescience Database Archive (English)

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Dicty_cDB: Contig-U06413-1 [Dicty_cDB

Lifescience Database Archive (English)

Full Text Available rus EST library project... 48 0.34 1 ( EY496038 ) CBBP2673.rev CBBP Hirudo medicinalis hermaphrodit... 48 0....34 1 ( EY493522 ) CBBP19513.fwd CBBP Hirudo medicinalis hermaphrodi... 48 0.34 1 ( EY491706 ) CBBP18426.fwd CBBP Hirudo medicina...lis hermaphrodi... 48 0.34 1 ( EY491705 ) CBBP18426.rev CBBP Hirudo medicina...lis hermaphrodi... 48 0.34 1 ( EY490129 ) CBBP17464.fwd CBBP Hirudo medicinalis hermaphrodi...... 48 0.34 1 ( EY485788 ) CBBP14812.fwd CBBP Hirudo medicinalis hermaphrodi... 48 0.34 1 ( EY485787 ) CBBP14812.rev CBBP Hirudo medici

Epidermal growth factor receptor coexpression modulates susceptibility to Herceptin in HER2/neu overexpressing breast cancer cells via specific erbB-receptor interaction and activation

International Nuclear Information System (INIS)

Diermeier, Simone; Horvath, Gabor; Knuechel-Clarke, Ruth; Hofstaedter, Ferdinand; Szoellosi, Janos; Brockhoff, Gero

2005-01-01

Background: Growth factors and Herceptin specifically and differentially modulate cell proliferation of tumor cells. However, the mechanism of action on erbB-receptor level is incompletely understood. We evaluated Herceptin's capacity to modulate erbB-receptor activation and interaction on the cell surface level and thereby potentially impair cell proliferation of HER2/neu (c-erbB2) overexpressing breast cancer cells, both in the presence and absence of relevant growth factors. Methods: BT474 and SK-BR-3 breast cancer cell lines were treated with Epidermal Growth Factor (EGF), Heregulin, and with Herceptin in different combinations. Kinetics of cell proliferation were evaluated flow cytometrically based on BrdU-labeling. Fluorescence Resonance Energy Transfer, ELISAs and phosphorylation site specific Western Blotting was performed to investigate erbB-receptor interaction and activation. Results: EGF induced EGFR/EGFR and EGFR/c-erbB2 interactions correlate with stimulation of cell proliferation in BT474 cells. Both homo- and heterodimerization are considerably less pronounced in SK-BR-3 cells and heterointeraction is additionally reduced by EGF treatment, causing inhibition of cell proliferation. Heregulin stimulates cell proliferation extensively in both cell lines. Herceptin drives BT474 cells more efficiently into quiescence than it does with SK-BR-3 cells and thereby blocks cell cycle progress. In SK-BR-3 Herceptin treatment causes c-erbB2 phosphorylation of Y877 and Y1248, EGF induces Y877 and Y1112 phosphorylation. The Y1112 phosphorylation site, activated by EGF in SK-BR-3 cell, is bypassed in BT474. In addition the inhibitory capacity of Herceptin on BT474 and SK-BR-3 cell proliferation depends on the presence and absence of growth factors to a various extent. Conclusion: The growth inhibitory effect of Herceptin on c-erbB2 overexpressing breast cancer cells is considerably modulated by EGFR coexpression and consequently EGFR/c-erbB2 homo- and

ErbB2 Pathway Activation upon Smad4 Loss Promotes Lung Tumor Growth and Metastasis.

Science.gov (United States)

Liu, Jian; Cho, Sung-Nam; Akkanti, Bindu; Jin, Nili; Mao, Jianqiang; Long, Weiwen; Chen, Tenghui; Zhang, Yiqun; Tang, Ximing; Wistub, Ignacio I; Creighton, Chad J; Kheradmand, Farrah; DeMayo, Francesco J

2015-03-03

Lung cancer remains the leading cause of cancer death. Genome sequencing of lung tumors from patients with squamous cell carcinoma has identified SMAD4 to be frequently mutated. Here, we use a mouse model to determine the molecular mechanisms by which Smad4 loss leads to lung cancer progression. Mice with ablation of Pten and Smad4 in airway epithelium develop metastatic adenosquamous tumors. Comparative transcriptomic and in vivo cistromic analyses determine that loss of PTEN and SMAD4 results in ELF3 and ErbB2 pathway activation due to decreased expression of ERRFI1, a negative regulator of ERBB2 in mouse and human cells. The combinatorial inhibition of ErbB2 and Akt signaling attenuate tumor progression and cell invasion, respectively. Expression profile analysis of human lung tumors substantiated the importance of the ErbB2/Akt/ELF3 signaling pathway as both a prognostic biomarker and a therapeutic drug target for treating lung cancer. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Exercise training and return to a well-balanced diet activate the neuregulin 1/ErbB pathway in skeletal muscle of obese rats

Science.gov (United States)

Ennequin, Gaël; Boisseau, Nathalie; Caillaud, Kevin; Chavanelle, Vivien; Gerbaix, Maude; Metz, Lore; Etienne, Monique; Walrand, Stéphane; Masgrau, Aurélie; Guillet, Christelle; Courteix, Daniel; Niu, Airu; Li, Yi-Ping; Capel, Fréderic; Sirvent, Pascal

2015-01-01

Some studies suggest that the signalling pathway of neuregulin 1 (NRG1), a protein involved in the regulation of skeletal muscle metabolism, could be altered by nutritional and exercise interventions. We hypothesized that diet-induced obesity could lead to alterations of the NRG1 signalling pathway and that chronic exercise could improve NRG1 signalling in rat skeletal muscle. To test this hypothesis, male Wistar rats received a high fat/high sucrose (HF/HS) diet for 16 weeks. At the end of this period, NRG1 and ErbB expression/activity in skeletal muscle was assessed. The obese rats then continued the HF/HS diet or were switched to a well-balanced diet. Moreover, in both groups, half of the animals also performed low intensity treadmill exercise training. After another 8 weeks, NRG1 and ErbB expression/activity in skeletal muscle were tested again. The 16 week HF/HS diet induced obesity, but did not significantly affect the NRG1/ErbB signalling pathway in rat skeletal muscle. Conversely, after the switch to a well-balanced diet, NRG1 cleavage ratio and ErbB4 amount were increased. Chronic exercise training also promoted NRG1 cleavage, resulting in increased ErbB4 phosphorylation. This result was associated with increased protein expression and phosphorylation ratio of the metalloprotease ADAM17, which is involved in NRG1 shedding. Similarly, in vitro stretch-induced activation of ADAM17 in rat myoblasts induced NRG1 cleavage and ErbB4 activation. These results show that low intensity endurance training and well-balanced diet activate the NRG1-ErbB4 pathway, possibly via the metalloprotease ADAM17, in skeletal muscle of diet-induced obese rats. PMID:25820551

No evidence for c-erbB-2 overexpression in gastric carcinogenesis

NARCIS (Netherlands)

Blok, P.; Craanen, M. E.; Dekker, W.; Offerhaus, G. J.; Tytgat, G. N.

1998-01-01

Conflicting data on c-erbB-2 overexpression in gastric carcinomas can be found in the literature with regard to overall prevalence, prognostic significance and the histological type according to Lauren. The majority of these studies have focused on advanced gastric carcinomas whereas data on

Dicty_cDB: Contig-U03947-1 [Dicty_cDB

Lifescience Database Archive (English)

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Dicty_cDB: Contig-U16335-1 [Dicty_cDB

Lifescience Database Archive (English)

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Novel Peptide/Protein Delivery System Targeting erbB2-Overexpressing Breast Cancer Cells

National Research Council Canada - National Science Library

Yu, Dihua

2002-01-01

.... During this funding year, we focused on the delivery of erbB2 signal-blocking ESP peptides (objective 2) . Because of the complexity of biotin-penetratin-AHNP-ESP, the synthesis was unsuccessful...

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

Directory of Open Access Journals (Sweden)

Anxin Gu

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

Defining the ATM-mediated barrier to tumorigenesis in somatic mammary cells following ErbB2 activation.

Science.gov (United States)

Reddy, Jay P; Peddibhotla, Sirisha; Bu, Wen; Zhao, Jing; Haricharan, Svasti; Du, Yi-Chieh Nancy; Podsypanina, Katrina; Rosen, Jeffrey M; Donehower, Larry A; Li, Yi

2010-02-23

p53, apoptosis, and senescence are frequently activated in preneoplastic lesions and are barriers to progression to malignancy. These barriers have been suggested to result from an ATM-mediated DNA damage response (DDR), which may follow oncogene-induced hyperproliferation and ensuing DNA replication stress. To elucidate the currently untested role of DDR in breast cancer initiation, we examined the effect of oncogene expression in several murine models of breast cancer. We did not observe a detectable DDR in early hyperplastic lesions arising in transgenic mice expressing several different oncogenes. However, DDR signaling was strongly induced in preneoplastic lesions arising from individual mammary cells transduced in vivo by retroviruses expressing either PyMT or ErbB2. Thus, activation of an oncogene after normal tissue development causes a DDR. Furthermore, in this somatic ErbB2 tumor model, ATM, and thus DDR, is required for p53 stabilization, apoptosis, and senescence. In palpable tumors in this model, p53 stabilization and apoptosis are lost, but unexpectedly senescence remains in many tumor cells. Thus, this murine model fully recapitulates early DDR signaling; the eventual suppression of its endpoints in tumorigenesis provides compelling evidence that ErbB2-induced aberrant mammary cell proliferation leads to an ATM-mediated DDR that activates apoptosis and senescence, and at least the former must be overcome to progress to malignancy. This in vivo study also uncovers an unexpected effect of ErbB2 activation previously known for its prosurvival roles, and suggests that protection of the ATM-mediated DDR-p53 signaling pathway may be important in breast cancer prevention.

Dicty_cDB: Contig-U15540-1 [Dicty_cDB

Lifescience Database Archive (English)

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In silico prediction of ErbB signal activation from receptor expression ...

Indian Academy of Sciences (India)

85

Annals of biomedical engineering 35 1012-1025. Machado D, Costa RS, Rocha M, Ferreira EC, Tidor B, Rocha I 2011 Modeling formalisms in Systems Biology. AMB Express 1 45. McCabe Pryor M, et al. 2015 Orchestration of ErbB3 signaling through heterointeractions and homointeractions. Mol Biol Cell 26 4109-4123.

The sorting protein PACS-2 promotes ErbB signalling by regulating recycling of the metalloproteinase ADAM17

DEFF Research Database (Denmark)

Dombernowsky, Sarah Louise; Samsøe-Petersen, Jacob; Petersen, Camilla Hansson

2015-01-01

The metalloproteinase ADAM17 activates ErbB signalling by releasing ligands from the cell surface, a key step underlying epithelial development, growth and tumour progression. However, mechanisms acutely controlling ADAM17 cell-surface availability to modulate the extent of ErbB ligand release....... PACS-2 co-localizes with ADAM17 on early endosomes and PACS-2 knockdown decreases the recycling and stability of internalized ADAM17. Hence, PACS-2 sustains ADAM17 cell-surface activity by diverting ADAM17 away from degradative pathways. Interestingly, Pacs2-deficient mice display significantly reduced...

RUNX1 positively regulates the ErbB2/HER2 signaling pathway through modulating SOS1 expression in gastric cancer cells.

Science.gov (United States)

Mitsuda, Yoshihide; Morita, Ken; Kashiwazaki, Gengo; Taniguchi, Junichi; Bando, Toshikazu; Obara, Moeka; Hirata, Masahiro; Kataoka, Tatsuki R; Muto, Manabu; Kaneda, Yasufumi; Nakahata, Tatsutoshi; Liu, Pu Paul; Adachi, Souichi; Sugiyama, Hiroshi; Kamikubo, Yasuhiko

2018-04-23

The dual function of runt-related transcriptional factor 1 (RUNX1) as an oncogene or oncosuppressor has been extensively studied in various malignancies, yet its role in gastric cancer remains elusive. Up-regulation of the ErbB2/HER2 signaling pathway is frequently-encountered in gastric cancer and contributes to the maintenance of these cancer cells. This signaling cascade is partly mediated by son of sevenless homolog (SOS) family, which function as adaptor proteins in the RTK cascades. Herein we report that RUNX1 regulates the ErbB2/HER2 signaling pathway in gastric cancer cells through transactivating SOS1 expression, rendering itself an ideal target in anti-tumor strategy toward this cancer. Mechanistically, RUNX1 interacts with the RUNX1 binding DNA sequence located in SOS1 promoter and positively regulates it. Knockdown of RUNX1 led to the decreased expression of SOS1 as well as dephosphorylation of ErbB2/HER2, subsequently suppressed the proliferation of gastric cancer cells. We also found that our novel RUNX inhibitor (Chb-M') consistently led to the deactivation of the ErbB2/HER2 signaling pathway and was effective against several gastric cancer cell lines. Taken together, our work identified a novel interaction of RUNX1 and the ErbB2/HER2 signaling pathway in gastric cancer, which can potentially be exploited in the management of this malignancy.

Molecularly targeted therapy for the treatment of head and neck cancer: a review of the ErbB family inhibitors

Directory of Open Access Journals (Sweden)

Sacco AG

2016-04-01

Full Text Available Assuntina G Sacco,1 Francis P Worden2 1Department of Internal Medicine, Division of Hematology/Oncology, University of California at San Diego Moores Cancer Center, La Jolla, CA, USA; 2Department of Internal Medicine, Division of Hematology/Oncology, University of Michigan Health System, Ann Arbor, MI, USA Abstract: The majority of patients with head and neck squamous cell carcinoma (HNSCC present with locally advanced disease, which requires site-specific combinations of surgery, radiation, and chemotherapy. Despite aggressive therapy, survival outcomes remain poor, and treatment-related morbidity is not negligible. For patients with recurrent or metastatic disease, therapeutic options are further limited and prognosis is dismal. With this in mind, molecularly targeted therapy provides a promising approach to optimizing treatment efficacy while minimizing associated toxicity. The ErbB family of receptors (ie, epidermal growth factor receptor [EGFR], ErbB2/human epidermal growth factor receptor [HER]-2, ErbB3/HER3, and ErbB4/HER4 is known to contribute to oncogenic processes, such as cellular proliferation and survival. EGFR, specifically, is upregulated in more than 90% of HNSCC, has been implicated in radiation resistance, and correlates with poorer clinical outcomes. The central role of EGFR in the pathogenesis of HNSCC suggests that inhibition of this pathway represents an attractive treatment strategy. As a result, EGFR inhibition has been extensively studied, with the emergence of two classes of drug therapy: monoclonal antibodies and tyrosine kinase inhibitors. While the monoclonal antibody cetuximab is currently the only US Food and Drug Administration–approved EGFR inhibitor for the treatment of HNSCC, numerous investigational drugs are being evaluated in clinical trials. This paper will review the role of the ErbB family in the pathogenesis of HNSCC, as well as the evidence-based data for the use of ErbB family inhibition in clinical

Earth Radiation Budget Experiment (ERBE) Data Sets for Global Environment and Climate Change Studies

Science.gov (United States)

Bess, T. Dale; Carlson, Ann B.; Denn, Fredrick M.

1997-01-01

For a number of years there has been considerable interest in the earth's radiation budget (ERB) or energy balance, and entails making the best measurements possible of absorbed solar radiation, reflected shortwave radiation (RSW), thermal outgoing longwave radiation (OLR), and net radiation. ERB data are fundamental to the development of realistic climate models and studying natural and anthropogenic perturbations of the climate. Much of the interest and investigations in the earth's energy balance predated the age of earth-orbiting satellites (Hunt et al., 1986). Beginning in the mid 1960's earth-orbiting satellites began to play an important role in making measurements of the earth's radiation flux although much effort had gone into measuring ERB parameters prior to 1960 (House et al., 1986). Beginning in 1974 and extending until the present time, three different satellite experiments (not all operating at the same time) have been making radiation budget measurements almost continually in time. Two of the experiments were totally dedicated to making radiation budget measurements of the earth, and the other experiment flown on NOAA sun-synchronous AVHRR weather satellites produced radiation budget parameters as a by-product. The heat budget data from the AVHRR satellites began collecting data in June 1974 and have operated almost continuously for 23 years producing valuable data for long term climate monitoring.

Dicty_cDB: Contig-U10237-1 [Dicty_cDB

Lifescience Database Archive (English)

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Dicty_cDB: Contig-U15132-1 [Dicty_cDB

Lifescience Database Archive (English)

Full Text Available s) Value N ( C22922 ) Dictyostelium discoideum gamete cDNA, clone FC-AM03. 1122 0.0 1 ( EY489954 ) CBBP17356.rev CBBP Hirudo medicina...lis hermaphrodi... 56 9e-12 4 ( EY481037 ) CBBP11163.rev CBBP Hirudo medicinalis he...( CZ542454 ) SRAA-aad44c05.g1 Strongyloides ratti whole genome... 66 1e-10 3 ( EY491469 ) CBBP18281.fwd CBBP Hirudo medicina...lis hermaphrodi... 56 3e-10 2 ( EY481038 ) CBBP11163.fwd CBBP Hirudo medicina...lis hermaphrodi... 56 3e-10 2 ( EY489955 ) CBBP17356.fwd CBBP Hirudo medicinalis hermaphrodi...

Contribution of EGFR and ErbB-3 Heterodimerization to the EGFR Mutation-Induced Gefitinib- and Erlotinib-Resistance in Non-Small-Cell Lung Carcinoma Treatments.

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Debby D Wang

Full Text Available EGFR mutation-induced drug resistance has become a major threat to the treatment of non-small-cell lung carcinoma. Essentially, the resistance mechanism involves modifications of the intracellular signaling pathways. In our work, we separately investigated the EGFR and ErbB-3 heterodimerization, regarded as the origin of intracellular signaling pathways. On one hand, we combined the molecular interaction in EGFR heterodimerization with that between the EGFR tyrosine kinase and its inhibitor. For 168 clinical subjects, we characterized their corresponding EGFR mutations using molecular interactions, with three potential dimerization partners (ErbB-2, IGF-1R and c-Met of EGFR and two of its small molecule inhibitors (gefitinib and erlotinib. Based on molecular dynamics simulations and structural analysis, we modeled these mutant-partner or mutant-inhibitor interactions using binding free energy and its components. As a consequence, the mutant-partner interactions are amplified for mutants L858R and L858R_T790M, compared to the wild type EGFR. Mutant delL747_P753insS represents the largest difference between the mutant-IGF-1R interaction and the mutant-inhibitor interaction, which explains the shorter progression-free survival of an inhibitor to this mutant type. Besides, feature sets including different energy components were constructed, and efficient regression trees were applied to map these features to the progression-free survival of an inhibitor. On the other hand, we comparably examined the interactions between ErbB-3 and its partners (EGFR mutants, IGF-1R, ErbB-2 and c-Met. Compared to others, c-Met shows a remarkably-strong binding with ErbB-3, implying its significant role in regulating ErbB-3 signaling. Moreover, EGFR mutants corresponding to poor clinical outcomes, such as L858R_T790M, possess lower binding affinities with ErbB-3 than c-Met does. This may promote the communication between ErbB-3 and c-Met in these cancer cells. The

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

International Nuclear Information System (INIS)

Kyotani, Yoji; Ota, Hiroyo; Itaya-Hironaka, Asako; Yamauchi, Akiyo; Sakuramoto-Tsuchida, Sumiyo; Zhao, Jing; Ozawa, Kentaro; Nagayama, Kosuke; Ito, Satoyasu; Takasawa, Shin; Kimura, Hiroshi; Uno, Masayuki; Yoshizumi, Masanori

2013-01-01

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

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

Energy Technology Data Exchange (ETDEWEB)

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

2013-11-15

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

Osteossarcomas humanos de alto grau: imunoexpressão de p53, erb-2 e P-glicoproteína, e correlação com o parâmetro anaplasia P-glycoprotein, erb2 and p53 expression in high-grade human osteosarcomas and their correlation with anaplasia

Directory of Open Access Journals (Sweden)

Maria Teresa de Seixas Alves

2008-04-01

Full Text Available INTRODUÇÃO: Osteossarcoma (OS, o mais freqüente tumor primário maligno do osso, tem comportamento local agressivo e alto índice de disseminação sistêmica. Os eventos que permitem o crescimento e a disseminação tumoral ainda permanecem controversos. Os estudos sobre a carcinogênese e a progressão dessa neoplasia, com base na imunoexpressão de c-erb-B2, P-glicoproteína (P-gp e p53, apresentam resultados conflitantes acerca do real valor prognóstico e suas correlações com parâmetros histológicos. A anaplasia, em neoplasias na infância, constitui parâmetro histológico de agressividade tumoral e quimiorresistência. Nos OS primários ou metastáticos, seu significado permanece controverso. Por outro lado, em outras neoplasias humanas, a expressão do c-erb-B2 relaciona-se com p53, grau nuclear e outros parâmetros de agressividade. OBJETIVO: Avaliar a imunoexpressão de p53, c-erb-B2 e P-gp em OS, correlacionando os par��metros entre si e com a presença de anaplasia. MÉTODO: O estudo incluiu 96 biópsias pré-quimioterapia de pacientes com OS de alto grau, diagnosticados entre 1991 e 2000. A pesquisa imuno-histoquímica de p53, P-gp e c-erb-B2 foi feita pela técnica da estreptoavidina-biotina-peroxidase. Foram considerados positivos os casos onde havia imunoexpressão em 10% ou mais das células neoplásicas. Somente colorações membranosa (para cerb-B2 e P-gp e nuclear (para p53 foram consideradas positivas. Anaplasia foi definida como no tumor de Wilms, sendo considerada presente ou ausente. RESULTADOS: Anaplasia pôde ser avaliada em 82/96 casos, estando presente em 29 (35,36%. Imunoexpressão de p53 foi detectada em 25 dos 60 casos (36,23%; de P-gp, em 30 dos 73 casos (41,1%; e de c-erb-B2, em 22 dos 55 casos (40%. Os resultados demonstraram associação entre as imunoexpressões de c-erb-B2 e p53 (p = 0,042, p53 e o parâmetro anaplasia (p = 0,015, anaplasia e Pg (p = 0.034 CONCLUSÕES: A imunoexpressão de p53, c-erb

[Construction of the lentiviral expression vector for anti-p185(erbB2) mouse/human chimeric antibody].

Science.gov (United States)

Liu, Fang; Li, Li; Zhang, Wei; Wang, Qi

2013-04-01

This research was to construct the lentiviral expression vector for anti- p185(erbB2) mouse/human chimeric antibody and to determine the expression of the chimeric antibody gene in 293T cells transfected with this vector. The genes (vL and vH) coding light and heavy chain of variable regions of anti-p185(erbB2) mAb and the constant regions of human IgG1 (kappa and gamma1) were cloned with PCR method. The target genes were assembled by three-primers PCR method to obtain the chimeric light chain (L) and the chimeric heavy chain (H). Both chains inserted into the down stream and upper stream of IRES gene of the plasmid pVAX1/IRES respectively. We digested the plasmid pVAX1/ H-IRES-L with endoenzyme and subcloned H-IRES-L into the lentiviral vector pWPI. The enzyme digestion and sequence analysis showed that the lentiviral expression vector pWPI/H-IRES-L was constructed correctly. Then, it was transfected into 293T cells and after 48h, GFP protein expression in 293T cells were detected by fluorescent microscope and the chimeric antibody expression was detected by RT-PCR and direct ELISA. The results showed that after 293T cells were transfected with recombination plasmid, both light and heavy chains of the chimeric antibody genes could express together. The chimeric antibody expressed could bind to p185(erbB2) specifically. This research may lay a sound foundation for further study of anti-p185(erbB2) engineered antibody.

Anti-metastasis activity of black rice anthocyanins against breast cancer: analyses using an ErbB2 positive breast cancer cell line and tumoral xenograft model.

Science.gov (United States)

Luo, Li-Ping; Han, Bin; Yu, Xiao-Ping; Chen, Xiang-Yan; Zhou, Jie; Chen, Wei; Zhu, Yan-Feng; Peng, Xiao-Li; Zou, Qiang; Li, Sui-Yan

2014-01-01

Increasing evidence from animal, epidemiological and clinical investigations suggest that dietary anthocyanins have potential to prevent chronic diseases, including cancers. It is also noteworthy that human epidermal growth factor receptor 2 (ErbB2) protein overexpression or ErbB2 gene amplification has been included as an indicator for metastasis and higher risk of recurrence for breast cancer. The present experiments investigated the anti-metastasis effects of black rice anthocyanins (BRACs) on ErbB2 positive breast cancer cells in vivo and in vitro. Oral administration of BRACs (150 mg/kg/day) reduced transplanted tumor growth, inhibited pulmonary metastasis, and decreased lung tumor nodules in BALB/c nude mice bearing ErbB2 positive breast cancer cell MDA-MB-453 xenografts. The capacity for migration, adhesion, motility and invasion was also inhibited by BRACs in MDA-MB-453 cells in a concentration dependent manner, accompanied by decreased activity of a transfer promoting factor, urokinase-type plasminogen activator (u-PA). Together, our results indicated that BRACs possess anti-metastasis potential against ErbB2 positive human breast cancer cells in vivo and in vitro through inhibition of metastasis promoting molecules.

A novel mouse monoclonal antibody targeting ErbB2 suppresses breast cancer growth

Energy Technology Data Exchange (ETDEWEB)

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

2009-07-03

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

Breast cancer cells can switch between estrogen receptor alpha and ErbB signaling and combined treatment against both signaling pathways postpones development of resistance

DEFF Research Database (Denmark)

Sonne-Hansen, Katrine; Norrie, Ida C; Emdal, Kristina Bennet

2010-01-01

circumvent development of resistance. Limited effects were observed when targeting EGFR and ErbB2 with the monoclonal antibodies cetuximab, trastuzumab, and pertuzumab, whereas the pan-ErbB inhibitor CI-1033 selectively inhibited growth of fulvestrant resistant cell lines. CI-1033 inhibited Erk but not Akt...

Dicty_cDB: Contig-U16208-1 [Dicty_cDB

Lifescience Database Archive (English)

Full Text Available H306-1B3, complete sequ... 42 0.001 8 ( EY487360 ) CBBP15754.fwd CBBP Hirudo medicinalis hermaphrodi... 58 0....27 1 ( EY489283 ) CBBP16951.fwd CBBP Hirudo medicinalis hermaphrodi... 50 0.27 1 ( EY385189 ) CAXA5562.fwd ...ev CAWZ Helobdella robusta Primary Late... 42 0.37 2 ( EY485499 ) CBBP14631.fwd CBBP Hirudo medicinalis herm...zias latipes EST, clone M046--B11_093. 38 0.39 3 ( EY490006 ) CBBP17391.fwd CBBP Hirudo medicinalis hermaphr...odi... 44 0.39 2 ( EY485498 ) CBBP14631.rev CBBP Hirudo medicinalis hermaphrodi... 44 0.39 2 ( EY503416 ) CB

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

Directory of Open Access Journals (Sweden)

Lu Kun

2008-12-01

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

Relationship of PCNA, C-erbB2 and CD44s expression with tumor grade and stage in urothelial carcinomas of the bladder

Science.gov (United States)

Yıldırım, Ayhan; Kösem, Mustafa; Sayar, İlyas; Gelincik, İbrahim; Yavuz, Alparslan; Bozkurt, Aliseydi; Erkorkmaz, Ünal; Bayram, İrfan

2014-01-01

In the present study, the intention was to reveal the relationship of histological grade and stage with c-erbB2, CD44s, and PCNA immunoreactivity in bladder urothelial carcinomas (UC). In our study, we evaluated 46 items of transurethral resection material of patients submitted by YYU Faculty of Medicine, Main Department of Pathology, with a mass revealed in their bladder after clinical and radiological studies at our laboratories and who were diagnosed with urothelial carcinomas. PCNA, c-erbB2, and CD44s were applied in an immunohistochemical manner comprised from nine low-malignant potential papillary urothelial neoplasia, 23 low-grade papillary urothelial carcinoma, and 14 high-grade papillary urothelial carcinoma. Immunostaining was scored according to the percentage of positive cells. The immunohistochemical study demonstrated that the c-erbB2 and PCNA staining ratio increased when an increase occurred in stage and grade. The CD44s staining ratio decreased. C-erbB2, PCNA, and CD44s appear to be a useful marker in the assessment of the prognosis and treatment options in urothelial carcinomas. PMID:25035774

Dicty_cDB: Contig-U05033-1 [Dicty_cDB

Lifescience Database Archive (English)

Full Text Available 35269 Global-Ocean-Sampling_GS-34-01-01-1... 48 0.13 2 ( EY497680 ) CBBP3693.rev CBBP Hirudo medicinalis her...maphrodit... 50 0.13 1 ( EY493998 ) CBBP19771.rev CBBP Hirudo medicinalis hermaph...rodi... 50 0.13 1 ( EY487045 ) CBBP15563.fwd CBBP Hirudo medicinalis hermaphrodi... 50 0.13 1 ( EY487044 ) C...BBP15563.rev CBBP Hirudo medicinalis hermaphrodi... 50 0.13 1 ( AC116305 ) Dictyostelium discoideum chromoso

Dicty_cDB: Contig-U16085-1 [Dicty_cDB

Lifescience Database Archive (English)

Full Text Available from different dev... 32 9.9 2 ( EY479522 ) CBBP10319.fwd CBBP Hirudo medicinalis hermaphrodi... 32 9.9 2 ( ...EY497159 ) CBBP3379.fwd CBBP Hirudo medicinalis hermaphrodit... 32 9.9 2 ( EY4795...21 ) CBBP10319.rev CBBP Hirudo medicinalis hermaphrodi... 32 9.9 2 ( FK866718 ) 0000099873M20 D. serrata mRN...0.0 2 ( EY500591 ) CBBP5343.fwd CBBP Hirudo medicinalis hermaphrodit... 32 10.0 2 ( FK859392 ) 000004981173D

The chicken c-erbA alpha-product induces expression of thyroid hormone-responsive genes in 3,5,3'-triiodothyronine receptor-deficient rat hepatoma cells

DEFF Research Database (Denmark)

Muñoz, A; Höppner, W; Sap, J

1990-01-01

To determine the capacity of the chicken c-erbA (cTR-alpha) gene product in regulating expression of known thyroid hormone-responsive genes, both the cTR-alpha and the viral v-erbA genes were expressed in FAO cells, a rat hepatoma cell line defective for functional thyroid hormone receptors. Upon...

Cell cycle synchronization and BrdU incorporation as a tool to study the possible selective elimination of ErbB1 gene in the micronuclei in A549 cells

International Nuclear Information System (INIS)

Lauand, C.; Niero, E.L.; Dias, V.M.; Machado-Santelli, G.M.

2015-01-01

Lung cancer often exhibits molecular changes, such as the overexpression of the ErbB1 gene that encodes epidermal growth factor receptor (EGFR). ErbB1 amplification and mutation are associated with tumor aggressiveness and low response to therapy. The aim of the present study was to design a schedule to synchronize the cell cycle of A549 cell line (a non-small cell lung cancer) and to analyze the possible association between the micronuclei (MNs) and the extrusion of ErbB1 gene extra-copies. After double blocking, by the process of fetal bovine serum deprivation and vincristine treatment, MNs formation was monitored with 5-bromo-2-deoxyuridine (BrdU) incorporation, which is an S-phase marker. Statistical analyses allowed us to infer that MNs may arise both in mitosis as well as in interphase. The MNs were able to replicate their DNA and this process seemed to be non-synchronous with the main cell nuclei. The presence of ErbB1 gene in the MNs was evaluated by fluorescent in situ hybridization (FISH). ErbB1 sequences were detected in the MNs, but a relation between the MNs formation and extrusion of amplified ErbB1could not be established. The present study sought to elucidate the meaning of MNs formation and its association with the elimination of oncogenes or other amplified sequences from the tumor cells

Cell cycle synchronization and BrdU incorporation as a tool to study the possible selective elimination of ErbB1 gene in the micronuclei in A549 cells

Energy Technology Data Exchange (ETDEWEB)

Lauand, C.; Niero, E.L.; Dias, V.M.; Machado-Santelli, G.M. [Departamento de Biologia Celular e do Desenvolvimento, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, SP (Brazil)

2015-03-06

Lung cancer often exhibits molecular changes, such as the overexpression of the ErbB1 gene that encodes epidermal growth factor receptor (EGFR). ErbB1 amplification and mutation are associated with tumor aggressiveness and low response to therapy. The aim of the present study was to design a schedule to synchronize the cell cycle of A549 cell line (a non-small cell lung cancer) and to analyze the possible association between the micronuclei (MNs) and the extrusion of ErbB1 gene extra-copies. After double blocking, by the process of fetal bovine serum deprivation and vincristine treatment, MNs formation was monitored with 5-bromo-2-deoxyuridine (BrdU) incorporation, which is an S-phase marker. Statistical analyses allowed us to infer that MNs may arise both in mitosis as well as in interphase. The MNs were able to replicate their DNA and this process seemed to be non-synchronous with the main cell nuclei. The presence of ErbB1 gene in the MNs was evaluated by fluorescent in situ hybridization (FISH). ErbB1 sequences were detected in the MNs, but a relation between the MNs formation and extrusion of amplified ErbB1could not be established. The present study sought to elucidate the meaning of MNs formation and its association with the elimination of oncogenes or other amplified sequences from the tumor cells.

Crystallization and preliminary crystallographic studies of the single-chain variable fragment of antibody chA21 in complex with an N-terminal fragment of ErbB2

International Nuclear Information System (INIS)

Liu, Yang; Zhou, Huihao; Zhu, Juanjuan; Gao, Yongxiang; Niu, Liwen; Liu, Jing; Teng, Maikun

2009-01-01

An antibody–antigen complex consisting of a single-chain variable fragment of the potential therapeutic antibody chA21 and an N-terminal fragment (residues 1–192) of the human ErbB2 extracellular domain was expressed, purified and crystallized. X-ray diffraction data were collected to 2.45 Å resolution. ErbB2 is a transmembrane tyrosine kinase, the overexpression of which causes abnormality and disorder in cell signalling and leads to cell transformation. Previously, an anti-ErbB2 single-chain chimeric antibody chA21 that specifically inhibits the growth of ErbB2-overexpressing cancer cells in vitro and in vivo was developed. Here, an antibody–antigen complex consisting of the single-chain variable fragment (scFv) of chA21 and an N-terminal fragment (residues 1–192, named EP I) of the ErbB2 extracellular domain was crystallized using the sitting-drop vapour-diffusion method. An X-ray diffraction data set was collected to 2.45 Å resolution from a single flash-cooled crystal; the crystal belonged to space group P2 1 2 1 2 1

Detection of survivin, carcinoembryonic antigen and ErbB2 level in oral squamous cell carcinoma patients.

Science.gov (United States)

Li, Shu-Xia; Yang, Yan-Qi; Jin, Li-Jian; Cai, Zhi-Gang; Sun, Zheng

2016-01-01

The aim of this study was to detect the survivin, carcinoembryonic antigen (CEA) and ErbB2 in the saliva, serum and local tumor-exfoliated cells of oral squamous cell carcinoma (OSCC) patients, for providing reliable tumor markers for the early detection of oral malignant cancer. The saliva, serum, and local tumor-exfoliated cell samples of 26 OSCC patients without chemotherapy and 10 non-cancer patients were collected in Department of Oral and Maxillofacial Surgery, School of Stomatology, Peking University. The contents of survivin, CEA and ErbB2 using were detected usingenzyme-linked immunosorbent assay. The survivin and CEA levels in saliva and local tumor-exfoliated cells of OSCC patients were significantly higher than those in the non-cancer patients (P oral malignant cancer.

ERBB4 Mutations that Disrupt the Neuregulin-ErbB4 Pathway Cause Amyotrophic Lateral Sclerosis Type 19

Science.gov (United States)

Takahashi, Yuji; Fukuda, Yoko; Yoshimura, Jun; Toyoda, Atsushi; Kurppa, Kari; Moritoyo, Hiroyoko; Belzil, Veronique V.; Dion, Patrick A.; Higasa, Koichiro; Doi, Koichiro; Ishiura, Hiroyuki; Mitsui, Jun; Date, Hidetoshi; Ahsan, Budrul; Matsukawa, Takashi; Ichikawa, Yaeko; Moritoyo, Takashi; Ikoma, Mayumi; Hashimoto, Tsukasa; Kimura, Fumiharu; Murayama, Shigeo; Onodera, Osamu; Nishizawa, Masatoyo; Yoshida, Mari; Atsuta, Naoki; Sobue, Gen; Fifita, Jennifer A.; Williams, Kelly L.; Blair, Ian P.; Nicholson, Garth A.; Gonzalez-Perez, Paloma; Brown, Robert H.; Nomoto, Masahiro; Elenius, Klaus; Rouleau, Guy A.; Fujiyama, Asao; Morishita, Shinichi; Goto, Jun; Tsuji, Shoji

2013-01-01

Amyotrophic lateral sclerosis (ALS) is a devastating neurological disorder characterized by the degeneration of motor neurons and typically results in death within 3–5 years from onset. Familial ALS (FALS) comprises 5%–10% of ALS cases, and the identification of genes associated with FALS is indispensable to elucidating the molecular pathogenesis. We identified a Japanese family affected by late-onset, autosomal-dominant ALS in which mutations in genes known to be associated with FALS were excluded. A whole- genome sequencing and parametric linkage analysis under the assumption of an autosomal-dominant mode of inheritance with incomplete penetrance revealed the mutation c.2780G>A (p. Arg927Gln) in ERBB4. An extensive mutational analysis revealed the same mutation in a Canadian individual with familial ALS and a de novo mutation, c.3823C>T (p. Arg1275Trp), in a Japanese simplex case. These amino acid substitutions involve amino acids highly conserved among species, are predicted as probably damaging, and are located within a tyrosine kinase domain (p. Arg927Gln) or a C-terminal domain (p. Arg1275Trp), both of which mediate essential functions of ErbB4 as a receptor tyrosine kinase. Functional analysis revealed that these mutations led to a reduced autophosphorylation of ErbB4 upon neuregulin-1 (NRG-1) stimulation. Clinical presentations of the individuals with mutations were characterized by the involvement of both upper and lower motor neurons, a lack of obvious cognitive dysfunction, and relatively slow progression. This study indicates that disruption of the neuregulin-ErbB4 pathway is involved in the pathogenesis of ALS and potentially paves the way for the development of innovative therapeutic strategies such using NRGs or their agonists to upregulate ErbB4 functions. PMID:24119685

Evaluation of C-ErbB-2 Overexpression and Her-2/neu Gene Copy Number Heterogeneity in Barrett’s Adenocarcinoma

Directory of Open Access Journals (Sweden)

Axel Walch

2000-01-01

Full Text Available Amplifiction of the Her-2/neu gene is accompanied by overexpression of its cell surface receptor product, c‐erbB‐2 protein. To investigate the degree of intratumoural heterogeneity we applied immunohistochemistry in primary Barrett’s adenocarcinoma (BCA (n = 6 and dysplasia adjacent to the carcinoma (n = 4. In addition, fluorescence in situ hybridisation (FISH was performed in primary BCA (n=5 and dysplastic areas (n=4. For an objective evaluation digital image analysis and laser scanning microscopy were used. Five of six BCA showed a marked intratumoural heterogeneous staining pattern ranging from areas in which the tumour cells were negative or faintly positive to tumour areas with a strong staining of the entire membrane. Among the two dysplastic areas also a heterogenous staining pattern was observed. FISH analysis revealed marked heterogeneity of intratumoural gene copy number changes in all BCA showing populations with different fractions of cells with polysomy, low level amplification and high level amplification. One dysplasia showed a minor population with Her‐2/neu signal clusters. In conclusion, we observed marked intratumoural heterogeneity of c‐erbB‐2 protein overexpression and Her‐2/neu gene copy number in the majority of the primary BCA analyzed. Digital image analysis and laser scanning microscopy were helpful in quantifying the variations in protein expression and DNA copy number in individual tumour cells. The observed heterogeneity could hamper the exact diagnostic determination of the c‐erbB‐2 status in small biopsies and possibly influence the effectiveness of a potential c‐erbB‐2 targeting therapy.

The Regional Biomass-Energy Agency (ERBE): an opportunity for the biomass-energy development in Wallonia

International Nuclear Information System (INIS)

Lemaire, P.; Menu, J.F.; Belle, J.F. van; Schenkel, Y.

1997-01-01

In 1995, the European Commission (Directorate-General for Energy) and the Walloon government set up a biomass-energy agency (ERBE), to promote and build biomass-energy projects in Wallonia (Belgium). A survey of biomass-energy potential indicates that wood-energy seems to offer the best utilization opportunities. Forest and logging residues, sawmills' and joineries' off-cuts, pallets residues, etc. could be burnt in wood district heating units with a significant social benefit. Consequently, the ERBE Agency is trying to set up projects in this way in Austria (+/- 100 wood heating systems) or in Sweden. It serves to inform industries and municipalities about biomass-energy, to advise them in the building of biomass-energy projects, to identify their energy needs and their biomass resources, to carry out prefeasibility studies, to inform them about financing opportunities, and so on. (author)

Exercise training and return to a well-balanced diet activate the neuregulin 1/ErbB pathway in skeletal muscle of obese rats.

Science.gov (United States)

Ennequin, Gaël; Boisseau, Nathalie; Caillaud, Kevin; Chavanelle, Vivien; Gerbaix, Maude; Metz, Lore; Etienne, Monique; Walrand, Stéphane; Masgrau, Aurélie; Guillet, Christelle; Courteix, Daniel; Niu, Airu; Li, Yi-Ping; Capel, Fréderic; Sirvent, Pascal

2015-06-15

Some studies suggest that neuregulin 1 (NRG1) could be involved in the regulation of skeletal muscle energy metabolism in rodents. Here we assessed whether unbalanced diet is associated with alterations of the NRG1 signalling pathway and whether exercise and diet might restore NRG1 signalling in skeletal muscle of obese rats. We show that diet-induced obesity does not impair NRG1 signalling in rat skeletal muscle. We also report that endurance training and a well-balanced diet activate the NRG1 signalling in skeletal muscle of obese rats, possibly via a new mechanism mediated by the protease ADAM17. These results suggest that some beneficial effects of physical activity and diet in obese rats could be partly explained by stimulation of the NRG1 signalling pathway. Some studies suggest that the signalling pathway of neuregulin 1 (NRG1), a protein involved in the regulation of skeletal muscle metabolism, could be altered by nutritional and exercise interventions. We hypothesized that diet-induced obesity could lead to alterations of the NRG1 signalling pathway and that chronic exercise could improve NRG1 signalling in rat skeletal muscle. To test this hypothesis, male Wistar rats received a high fat/high sucrose (HF/HS) diet for 16 weeks. At the end of this period, NRG1 and ErbB expression/activity in skeletal muscle was assessed. The obese rats then continued the HF/HS diet or were switched to a well-balanced diet. Moreover, in both groups, half of the animals also performed low intensity treadmill exercise training. After another 8 weeks, NRG1 and ErbB expression/activity in skeletal muscle were tested again. The 16 week HF/HS diet induced obesity, but did not significantly affect the NRG1/ErbB signalling pathway in rat skeletal muscle. Conversely, after the switch to a well-balanced diet, NRG1 cleavage ratio and ErbB4 amount were increased. Chronic exercise training also promoted NRG1 cleavage, resulting in increased ErbB4 phosphorylation. This result was

A single amino acid substitution is sufficient to modify the mitogenic properties of the epidermal growth factor receptor to resemble that of gp185erbB-2

DEFF Research Database (Denmark)

Di Fiore, P P; Helin, K; Kraus, M H

1992-01-01

The epidermal growth factor (EGF) receptor (EGFR) and the erbB-2 gene product, gp185erbB-2, exhibit distinct abilities to stimulate mitogenesis in different target cells. By using chimeric molecules between these two receptors, we have previously shown that their intracellular juxtamembrane regio...

Polypeptide-based nanogels co-encapsulating a synergistic combination of doxorubicin with 17-AAG show potent anti-tumor activity in ErbB2-driven breast cancer models.

Science.gov (United States)

Desale, Swapnil S; Raja, Srikumar M; Kim, Jong Oh; Mohapatra, Bhopal; Soni, Kruti S; Luan, Haitao; Williams, Stetson H; Bielecki, Timothy A; Feng, Dan; Storck, Matthew; Band, Vimla; Cohen, Samuel M; Band, Hamid; Bronich, Tatiana K

2015-06-28

ErbB2-driven breast cancers constitute 20-25% of the cases diagnosed within the USA. The humanized anti-ErbB2 monoclonal antibody, Trastuzumab (Herceptin™; Genentech), with chemotherapy is the current standard of treatment. Novel agents and strategies continue to be explored, given the challenges posed by Trastuzumab-resistance development in most patients. The HSP90 inhibitor, 17-allylaminodemethoxygeldanamycin (17-AAG), which induces ErbB2 degradation and attenuates downstream oncogenic signaling, is one such agent that showed significant promise in early phase I and II clinical trials. Its low water solubility, potential toxicities and undesirable side effects observed in patients, partly due to the Cremophor-based formulation, have been discouraging factors in the advancement of this promising drug into clinical use. Encapsulation of 17-AAG into polymeric nanoparticle formulations, particularly in synergistic combination with conventional chemotherapeutics, represents an alternative approach to overcome these problems. Herein, we report an efficient co-encapsulation of 17-AAG and doxorubicin, a clinically well-established and effective modality in breast cancer treatment, into biodegradable and biocompatible polypeptide-based nanogels. Dual drug-loaded nanogels displayed potent cytotoxicity in a breast cancer cell panel and exerted selective synergistic anticancer activity against ErbB2-overexpressing breast cancer cell lines. Analysis of ErbB2 degradation confirmed efficient 17-AAG release from nanogels with activity comparable to free 17-AAG. Furthermore, nanogels containing both 17-AAG and doxorubicin exhibited superior antitumor efficacy in vivo in an ErbB2-driven xenograft model compared to the combination of free drugs. These studies demonstrate that polypeptide-based nanogels can serve as novel nanocarriers for encapsulating 17-AAG along with other chemotherapeutics, providing an opportunity to overcome solubility issues and thereby exploit its full

Development of the correlation study between mammographic appearances and expression of estrogen receptor, progesterone receptor and C-erbB-2 in patients with breast cancer

International Nuclear Information System (INIS)

Liu Jie; Liu Peifang

2012-01-01

Breast cancer is one of the most common female malignant tumors. The occurrence and development of breast cancer are often accompanied by abnormal gene expression. It has been well accepted that estrogen receptor (ER), progesterone receptor (PR) and C-erbB-2 (epidermal growth factor receptor-2) are the main reference indexes for clinical endocrine therapy and prognosis prediction. Oncogene expression reflects the malignant biological behavior of breast cancer from different perspectives. Those aggressive behaviors cause a variety of changes in histopathology and thus in imaging. Therefore, the imaging features of breast cancer may indirectly demonstrate the status of ER, PR and C-erbB-2 to a certain extent. Until now, because of its simple operation,low cost and high accuracy, mammography is still the preferred method in breast cancer screening and diagnosis, and has been proposed as a noninvasive technique for prediction of the expression of ER, PR and C-erbB-2. It has potential clinical value in preoperative assessment and non-surgical treatment for those who are not able to perform immunohistochemistry. This review summarized previous related studies and explored mammography as a noninvasive predictor for ER, PR and C-erbB-2. (authors)

78 FR 73586 - Senior Executive Service Performance Review Board (PRB) and Executive Resources Board (ERB...

Science.gov (United States)

2013-12-06

...: Performance Review Board Leland L. Gardner, Chairman Rachel D. Campbell, Member Craig M. Keats, Member Lucille Marvin, Alternate Member Executive Resources Board Rachel D. Campbell, Chairman Lucille Marvin, Member Joseph H. Dettmar, Alternate Member These changes to the PRB and ERB membership are due to the departure...

Expression Study of LeGAPDH, LeACO1, LeACS1A, and LeACS2 in Tomato Fruit (Solanum lycopersicum

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Pijar Riza Anugerah

2015-10-01

Full Text Available Tomato is a climacteric fruit, which is characterized by ripening-related increase of respiration and elevated ethylene synthesis. Ethylene is the key hormone in ripening process of climacteric fruits. The objective of this research is to study the expression of three ethylene synthesis genes: LeACO1, LeACS1A, LeACS2, and a housekeeping gene LeGAPDH in ripening tomato fruit. Specific primers have been designed to amplify complementary DNA fragment of LeGAPDH (143 bp, LeACO1 (240 bp, LeACS1A (169 bp, and LeACS2 (148 bp using polymerase chain reaction. Nucleotide BLAST results of the complementary DNA fragments show high similarity with LeGAPDH (NM_001247874.1, LeACO1 (NM_001247095.1, LeACS1A (NM_001246993.1, LeACS2 (NM_001247249.1, respectively. Expression study showed that LeACO1, LeACS1A, LeACS2, and LeGAPDH genes were expressed in ripening tomato fruit. Isolation methods, reference sequences, and primers used in this study can be used in future experiments to study expression of genes responsible for ethylene synthesis using quantitative polymerase chain reaction and to design better strategy for controlling fruit ripening in agroindustry.

Le laboratoire, le temple et le marché

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

De manière générale, les auteurs insistent sur le fait que c'est leur foi qui leur a .... nettement que dans de nombreux cercles, le besoin était vivement ressenti de ... Le Dr Kapur présente tout d'abord une brève discussion sur sa vision du ...... pour les soins aux enfants orphelins et aux pauvres et pour la renaissance des ...

Le rôle des chefs traditionnels au Ghana : un modèle inspirant ...

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

8 févr. 2011 ... Avec ses partenaires du Sud, avec aussi le soutien du Centre de recherches pour le développement international ( CRDI ), organisme canadien, Ray a étudié le rôle des chefs traditionnels au Ghana dans la lutte contre le VIH et le sida. Les collectivités politiques antérieures au colonialisme sont une ...

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

Directory of Open Access Journals (Sweden)

Fumitaka Koga

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

Rapport sur le développement dans le monde sur le thème du rôle ...

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

... rural et sont tributaires principalement de l'agriculture pour assurer leur subsistance. Ce projet permettra de veiller à ce qu'une place soit accordée aux travaux de recherche financés par le CRDI, aux points de vue différents et aux auteurs de l'hémisphère Sud dans le Rapport sur le développement dans le monde 2008.

A homologous form of human interleukin 16 is implicated in microglia recruitment following nervous system injury in leech Hirudo medicinalis.

Science.gov (United States)

Croq, Françoise; Vizioli, Jacopo; Tuzova, Marina; Tahtouh, Muriel; Sautiere, Pierre-Eric; Van Camp, Christelle; Salzet, Michel; Cruikshank, William W; Pestel, Joel; Lefebvre, Christophe

2010-11-01

In contrast to mammals, the medicinal leech Hirudo medicinalis can completely repair its central nervous system (CNS) after injury. This invertebrate model offers unique opportunities to study the molecular and cellular basis of the CNS repair processes. When the leech CNS is injured, microglial cells migrate and accumulate at the site of lesion, a phenomenon known to be essential for the usual sprouting of injured axons. In the present study, we demonstrate that a new molecule, designated HmIL-16, having functional homologies with human interleukin-16 (IL-16), has chemotactic activity on leech microglial cells as observed using a gradient of human IL-16. Preincubation of microglial cells either with an anti-human IL-16 antibody or with anti-HmIL-16 antibody significantly reduced microglia migration induced by leech-conditioned medium. Functional homology was demonstrated further by the ability of HmIL-16 to promote human CD4+ T cell migration which was inhibited by antibody against human IL-16, an IL-16 antagonist peptide or soluble CD4. Immunohistochemistry of leech CNS indicates that HmIL-16 protein present in the neurons is rapidly transported and stored along the axonal processes to promote the recruitment of microglial cells to the injured axons. To our knowledge, this is the first identification of a functional interleukin-16 homologue in invertebrate CNS. The ability of HmIL-16 to recruit microglial cells to sites of CNS injury suggests a role for HmIL-16 in the crosstalk between neurons and microglia in the leech CNS repair.

The negative cell cycle regulator, Tob (transducer of ErbB-2), is involved in motor skill learning

International Nuclear Information System (INIS)

Wang Xinming; Gao Xiang; Zhang Xuehan; Tu Yanyang; Jin Meilei; Zhao Guoping; Yu Lei; Jing Naihe; Li Baoming

2006-01-01

Tob (transducer of ErbB-2) is a negative cell cycle regulator with anti-proliferative activity in peripheral tissues. Our previous study identified Tob as a protein involved in hippocampus-dependent memory consolidation (M.L. Jin, X.M. Wang, Y.Y. Tu, X.H. Zhang, X. Gao, N. Guo, Z.Q. Xie, G.P. Zhao, N.H. Jing, B.M. Li, Y.Yu, The negative cell cycle regulator, Tob (Transducer of ErbB-2), is a multifunctional protein involved in hippocampus-dependent learning and memory, Neuroscience 131 (2005) 647-659). Here, we provide evidence that Tob in the central nervous system is engaged in acquisition of motor skill. Tob has a relatively high expression in the cerebellum. Tob expression is up-regulated in the cerebellum after rats receive training on a rotarod-running task. Rats infused with Tob antisense oligonucleotides into the 4th ventricle exhibit a severe deficit in running on a rotating rod or walking across a horizontally elevated beam

Le contrôle de gestion des entreprises familiales : un contrôle non-financiarisé ?

OpenAIRE

Barbelivien , Dominique

2016-01-01

Nous examinons la tendance décrite dans la littérature quant à la financiarisation de la fonction de contrôle de gestion en nous appuyant sur le cas d’une entreprise de taille intermédiaire familiale. Nous constatons que le contrôle de gestion dans le cas étudié correspond à une rationalisation des décisions opérationnelles et développons les raisons qui peuvent expliquer la persistance d’un contrôle de gestion très opérationnel. Le contexte d’entreprise familiale dans laquelle il y a confusi...

Das Erbe der Menschheit.

Directory of Open Access Journals (Sweden)

Joana Breidenbach

2005-09-01

Full Text Available Le concept d’« héritage » est apparu avec les efforts des États-nations occidentaux modernes émergents, au 19 e siècle, pour apporter une signification nationale à leurs paysages et à leurs environnements construits. Aujourd’hui, cependant, certains des moteurs centraux de ce mouvement de l’héritage sont des acteurs globaux plutôt que nationaux. Le projet le plus prestigieux pour la promotion de l’idée d’« héritage global » est la liste de l’Héritage mondial de l’ Unesco . Que deviennent les sites qui sont promus du statut d’héritage national à celui d’héritage global ? Deviennent-ils effectivement le véhicule d’une conscience globale partagée ? En se basant sur une recherche de terrain menée en Russie et en Chine, deux pays avec un tourisme de masse nouveau et émergent, nous arrivons à la conclusion que « les trésors de l’humanité entière » dans ces deux pays ne sont pas tant les sites d’une conscience planétaire que les véhicules de pédagogies postsocialistes hautement divergentes et qui reflètent les différentes traditions historiques, visions du développement, de la consommation et de la « belle vie », et structurations de l’ordre social opposées des deux pays. The concept of “heritage” arose as from nineteenth-century efforts by emergent modern Western nation-states to endow their landscapes and built environments with national significance. Today, however, some of the central activists of the heritage movement are global rather than national players. The highest-profile effort to promote the idea of a “global heritage” is Unesco ’s World Heritage list. What happens to sites that are promoted from national to global heritage status? Do they indeed become vehicles of a shared global consciousness? Based on fieldwork in Russia and China, two countries with a new and emergent mass tourism, we conclude that “the treasures of all humankind” in both countries

Comparative immunohistochemical expression of β-catenin, EGFR, ErbB2, and p63 in adamantinomatous and papillary craniopharyngiomas

International Nuclear Information System (INIS)

Eshebaa, Gh.E.; Hassan, A.A.

2015-01-01

Craniopharyngiomas (CPs) are rare epithelial tumors located mainly in the sellar/parasellar region. CPs have been classified into histopathologically, genetically, clinically and prognostically two distinctive subtypes: adamantinomatous and papillary variants. Aim To determine the immunohistochemical expression of β-catenin, EGFR, ErbB2, and p63 in adamantinomatous and papillary CPs. Materials and methods β-Catenin, EGFR, ErbB2, and p63 immunostaining was performed on paraffin embedded tissue sections of 25 CPs including 18 adamantinomatous craniopharyngioma (ACP) and 7 cases of papillary craniopharyngiomas (PCPs). Results 17 cases (94%) of ACP exhibited strong nuclear/cytoplasmic expression of β-catenin. On the contrary, all cases of PCP showed exclusively membranous expression (ρ value <0.0001). Regarding EGFR, 15 (83%) and 5 cases (71%) of APC and PCP respectively were positive. On the other hand, only 3 cases (17%) of APC and none of PCP exhibited positivity for ErbB2. p63 over-expression was observed in 16 cases of ACP (89%) and 6 cases of PCP (86%). However, the distribution of p63 staining was diffuse in ACP, while in PCP; the staining was mainly restricted to the basal cell layer. Conclusion Nuclear accumulation of β-catenin is a diagnostic hallmark of the ACP and is very helpful in the differential diagnosis between both ACP and PCP in the setting of small biopsies. Moreover, the restricted nuclear β-catenin accumulation in the cohesive cell clusters within the whorl-like areas supports that aberrant β-catenin expression may play a role in the morphogenesis of ACP.

Disruption of the ErbB signaling in adolescence increases striatal dopamine levels and affects learning and hedonic-like behavior in the adult mouse.

Science.gov (United States)

Golani, Idit; Tadmor, Hagar; Buonanno, Andres; Kremer, Ilana; Shamir, Alon

2014-11-01

The ErbB signaling pathway has been genetically and functionally implicated in schizophrenia. Numerous findings support the dysregulation of Neuregulin (NRG) and epidermal growth factor (EGF) signaling in schizophrenia. However, it is unclear whether alterations of these pathways in the adult brain or during development are involved in the pathophysiology of schizophrenia. Herein we characterized the behavioral profile and molecular changes resulting from pharmacologically blocking the ErbB signaling pathway during a critical period in the development of decision making, planning, judgments, emotions, social cognition and cognitive skills, namely adolescence. We demonstrate that chronic administration of the pan-ErbB kinase inhibitor JNJ-28871063 (JNJ) to adolescent mice elevated striatal dopamine levels and reduced preference for sucrose without affecting locomotor activity and exploratory behavior. In adulthood, adolescent JNJ-treated mice continue to consume less sucrose and needed significantly more correct-response trials to reach the learning criterion during the discrimination phase of the T-maze reversal learning task than their saline-injected controls. In addition, JNJ mice exhibited deficit in reference memory but not in working memory as measured in the radial arm maze. Inhibition of the pathway during adolescence did not affect exploratory behavior and locomotor activity in the open field, social interaction, social memory, and reversal learning in adult mice. Our data suggest that alteration of ErbB signaling during adolescence resulted in changes in the dopaminergic systems that emerge in pathological learning and hedonic behavior in adulthood, and pinpoints the possible role of the pathway in the development of cognitive skills and motivated behavior. Copyright © 2014 Elsevier B.V. and ECNP. All rights reserved.

A peptide conjugate of vitamin E succinate targets breast cancer cells with high erbB2 expression

Czech Academy of Sciences Publication Activity Database

Wang, X. F.; Birringer, M.; Dong, L.F.; Vepřek, Pavel; Low, P.; Swettenham, E.; Stantic, M.; Yuan, L. H.; Zobalová, Renata; Wu, K.; Ledvina, Miroslav; Ralph, S.J.; Neužil, Jiří

2007-01-01

Roč. 67, č. 7 (2007), s. 3337-3344 ISSN 0008-5472 R&D Projects: GA MZe QF3115 Institutional research plan: CEZ:AV0Z40550506; CEZ:AV0Z50520514 Keywords : vitamin e E * erbB2 * breast cancer Subject RIV: CC - Organic Chemistry Impact factor: 7.672, year: 2007

Structure and expression of two nuclear receptor genes in marsupials: insights into the evolution of the antisense overlap between the α-thyroid hormone receptor and Rev-erbα

Directory of Open Access Journals (Sweden)

Brown M Scott

2010-12-01

Full Text Available Abstract Background Alternative processing of α-thyroid hormone receptor (TRα, NR1A1 mRNAs gives rise to two functionally antagonistic nuclear receptors: TRα1, the α-type receptor, and TRα2, a non-hormone binding variant that is found only in mammals. TRα2 shares an unusual antisense coding overlap with mRNA for Rev-erbα (NR1D1, another nuclear receptor protein. In this study we examine the structure and expression of these genes in the gray short-tailed opossum, Monodelphis domestica, in comparison with that of eutherian mammals and three other marsupial species, Didelphis virginiana, Potorous tridactylus and Macropus eugenii, in order to understand the evolution and regulatory role of this antisense overlap. Results The sequence, expression and genomic organization of mRNAs encoding TRα1 and Rev-erbα are very similar in the opossum and eutherian mammals. However, the sequence corresponding to the TRα2 coding region appears truncated by almost 100 amino acids. While expression of TRα1 and Rev-erbα was readily detected in all tissues of M. domestica ages 0 days to 18 weeks, TRα2 mRNA was not detected in any tissue or stage examined. These results contrast with the widespread and abundant expression of TRα2 in rodents and other eutherian mammals. To examine requirements for alternative splicing of TRα mRNAs, a series of chimeric minigenes was constructed. Results show that the opossum TRα2-specific 5' splice site sequence is fully competent for splicing but the sequence homologous to the TRα2 3' splice site is not, even though the marsupial sequences are remarkably similar to core splice site elements in rat. Conclusions Our results strongly suggest that the variant nuclear receptor isoform, TRα2, is not expressed in marsupials and that the antisense overlap between TRα and Rev-erbα thus is unique to eutherian mammals. Further investigation of the TRα and Rev-erbα genes in marsupial and eutherian species promises to yield

Structure and expression of two nuclear receptor genes in marsupials: insights into the evolution of the antisense overlap between the α-thyroid hormone receptor and Rev-erbα

Science.gov (United States)

2010-01-01

Background Alternative processing of α-thyroid hormone receptor (TRα, NR1A1) mRNAs gives rise to two functionally antagonistic nuclear receptors: TRα1, the α-type receptor, and TRα2, a non-hormone binding variant that is found only in mammals. TRα2 shares an unusual antisense coding overlap with mRNA for Rev-erbα (NR1D1), another nuclear receptor protein. In this study we examine the structure and expression of these genes in the gray short-tailed opossum, Monodelphis domestica, in comparison with that of eutherian mammals and three other marsupial species, Didelphis virginiana, Potorous tridactylus and Macropus eugenii, in order to understand the evolution and regulatory role of this antisense overlap. Results The sequence, expression and genomic organization of mRNAs encoding TRα1 and Rev-erbα are very similar in the opossum and eutherian mammals. However, the sequence corresponding to the TRα2 coding region appears truncated by almost 100 amino acids. While expression of TRα1 and Rev-erbα was readily detected in all tissues of M. domestica ages 0 days to 18 weeks, TRα2 mRNA was not detected in any tissue or stage examined. These results contrast with the widespread and abundant expression of TRα2 in rodents and other eutherian mammals. To examine requirements for alternative splicing of TRα mRNAs, a series of chimeric minigenes was constructed. Results show that the opossum TRα2-specific 5' splice site sequence is fully competent for splicing but the sequence homologous to the TRα2 3' splice site is not, even though the marsupial sequences are remarkably similar to core splice site elements in rat. Conclusions Our results strongly suggest that the variant nuclear receptor isoform, TRα2, is not expressed in marsupials and that the antisense overlap between TRα and Rev-erbα thus is unique to eutherian mammals. Further investigation of the TRα and Rev-erbα genes in marsupial and eutherian species promises to yield additional insight into the

Epidermal Growth Factor Cytoplasmic Domain Affects ErbB Protein Degradation by the Lysosomal and Ubiquitin-Proteasome Pathway in Human Cancer Cells

Directory of Open Access Journals (Sweden)

Aleksandra Glogowska

2012-05-01

Full Text Available The cytoplasmic domains of EGF-like ligands, including EGF cytoplasmic domain (EGFcyt, have important biological functions. Using specific constructs and peptides of human EGF cytoplasmic domain, we demonstrate that EGFcyt facilitates lysosomal and proteasomal protein degradation, and this coincided with growth inhibition of human thyroid and glioma carcinoma cells. EGFcyt and exon 22–23-encoded peptide (EGF22.23 enhanced procathepsin B (procathB expression and procathB-mediated lysosomal degradation of EGFR/ErbB1 as determined by inhibitors for procathB and the lysosomal ATPase inhibitor BafA1. Presence of mbEGFctF, EGFcyt, EGF22.23, and exon 23-encoded peptides suppressed the expression of the deubiqitinating enzyme ubiquitin C-terminal hydrolase-L1 (UCH-L1. This coincided with hyperubiquitination of total cellular proteins and ErbB1/2 and reduced proteasome activity. Upon small interfering RNA-mediated silencing of endogenously expressed UCH-L1, a similar hyperubiquitinylation phenotype, reduced ErbB1/2 content, and attenuated growth was observed. The exon 23-encoded peptide region of EGFcyt was important for these biologic actions. Structural homology modeling of human EGFcyt showed that this molecular region formed an exposed surface loop. Peptides derived from this EGFcyt loop structure may aid in the design of novel peptide therapeutics aimed at inhibiting growth of cancer cells.

CERES ERBE-like Instantaneous TOA Estimates (ES-8) in HDF (CER_ES8_TRMM-PFM_Edition2)

Science.gov (United States)

Wielicki, Bruce A. (Principal Investigator)

The ES-8 archival data product contains a 24-hour, single-satellite, instantaneous view of scanner fluxes at the top-of-atmosphere (TOA) reduced from spacecraft altitude unfiltered radiances using Earth Radiation Budget Experiment (ERBE) scanner Inversion algorithms and the ERBE shortwave (SW) and longwave (LW) Angular Distribution Models (ADMs). The ES-8 also includes the total (TOT), SW, LW, and window (WN) channel radiometric data; SW, LW, and WN unfiltered radiance values; and the ERBE scene identification for each measurement. These data are organized according to the CERES 3.3-second scan into 6.6-second records. As long as there is one valid scanner measurement within a record, the ES-8 record will be generated. The following CERES ES8 data sets are currently available: CER_ES8_TRMM-PFM_Edition1 CER_ES8_TRMM-PFM_Edition2 CER_ES8_TRMM-PFM_Transient-Ops2 CER_ES8_Terra-FM1_Edition1 CER_ES8_Terra-FM2_Edition1 CER_ES8_Terra-FM1_Edition2 CER_ES8_Terra-FM2_Edition2 CER_ES8_Aqua-FM3_Edition1 CER_ES8_Aqua-FM4_Edition1 CER_ES8_Aqua-FM3_Edition2 CER_ES8_Aqua-FM4_Edition2 CER_ES8_Aqua-FM3_Edition1-CV CER_ES8_Aqua-FM4_Edition1-CV CER_ES8_Terra-FM1_Edition1-CV CER_ES8_Terra-FM1_Edition1-CV. [Location=GLOBAL] [Temporal_Coverage: Start_Date=1997-12-27; Stop_Date=2000-03-31] [Spatial_Coverage: Southernmost_Latitude=-90; Northernmost_Latitude=90; Westernmost_Longitude=-180; Easternmost_Longitude=180] [Data_Resolution: Temporal_Resolution=1 day; Temporal_Resolution_Range=Daily - < Weekly].

Selective Inhibition of Tumor Growth by Clonal NK Cells Expressing an ErbB2/HER2-Specific Chimeric Antigen Receptor

Science.gov (United States)

Schönfeld, Kurt; Sahm, Christiane; Zhang, Congcong; Naundorf, Sonja; Brendel, Christian; Odendahl, Marcus; Nowakowska, Paulina; Bönig, Halvard; Köhl, Ulrike; Kloess, Stephan; Köhler, Sylvia; Holtgreve-Grez, Heidi; Jauch, Anna; Schmidt, Manfred; Schubert, Ralf; Kühlcke, Klaus; Seifried, Erhard; Klingemann, Hans G; Rieger, Michael A; Tonn, Torsten; Grez, Manuel; Wels, Winfried S

2015-01-01

Natural killer (NK) cells are an important effector cell type for adoptive cancer immunotherapy. Similar to T cells, NK cells can be modified to express chimeric antigen receptors (CARs) to enhance antitumor activity, but experience with CAR-engineered NK cells and their clinical development is still limited. Here, we redirected continuously expanding and clinically usable established human NK-92 cells to the tumor-associated ErbB2 (HER2) antigen. Following GMP-compliant procedures, we generated a stable clonal cell line expressing a humanized CAR based on ErbB2-specific antibody FRP5 harboring CD28 and CD3ζ signaling domains (CAR 5.28.z). These NK-92/5.28.z cells efficiently lysed ErbB2-expressing tumor cells in vitro and exhibited serial target cell killing. Specific recognition of tumor cells and antitumor activity were retained in vivo, resulting in selective enrichment of NK-92/5.28.z cells in orthotopic breast carcinoma xenografts, and reduction of pulmonary metastasis in a renal cell carcinoma model, respectively. γ-irradiation as a potential safety measure for clinical application prevented NK cell replication, while antitumor activity was preserved. Our data demonstrate that it is feasible to engineer CAR-expressing NK cells as a clonal, molecularly and functionally well-defined and continuously expandable cell therapeutic agent, and suggest NK-92/5.28.z cells as a promising candidate for use in adoptive cancer immunotherapy. PMID:25373520

Dicty_cDB: Contig-U04644-1 [Dicty_cDB

Lifescience Database Archive (English)

Full Text Available pic... 44 2.2 1 ( EY502549 ) CBBP6429.rev CBBP Hirudo medicinalis hermaphrodit... 44 2.2 1 ( EY484983 ) CBBP14303.rev CBBP Hirudo med...icinalis hermaphrodi... 44 2.2 1 ( AM180255 ) Lawsonia i

ErbB-targeted CAR T-cell immunotherapy of cancer.

Science.gov (United States)

Whilding, Lynsey M; Maher, John

2015-01-01

Chimeric antigen receptor (CAR) based immunotherapy has been under development for the last 25 years and is now a promising new treatment modality in the field of cancer immunotherapy. The approach involves genetically engineering T cells to target malignant cells through expression of a bespoke fusion receptor that couples an HLA-independent antigen recognition domain to one or more intracellular T-cell activating modules. Multiple clinical trials are now underway in several centers to investigate CAR T-cell immunotherapy of diverse hematologic and solid tumor types. The most successful results have been achieved in the treatment of patients with B-cell malignancies, in whom several complete and durable responses have been achieved. This review focuses on the preclinical and clinical development of CAR T-cell immunotherapy of solid cancers, targeted against members of the ErbB family.

Le pompage optique naturel dans le milieu astrophysique

Science.gov (United States)

Pecker, J.-C.

The title of this lecture abstracts only a part of it : the importance in astrophysics of the study of non-LTE situations has become considerable, as well in the stellar atmospheres as, still more, in the study of fortuitous coincidences as a mechanism of formation of emission line nebular spectra, or of molecular interstellar « masers ». Another part of this talk underlines the role of Kastler in his time, and describes his warm personality through his public reactions in front of the nuclear armement, of the Viet-Nam and Algerian wars, of the problems of political refugees... Kastler was a great scientist ; he was also a courageous humanist. 1976 : Les accords nucléaires du Brésil : allocution d'ouverture (19 mars). Colloque sur le sujet ci-dessus. 1976 : La promotion de la culture dans le nouvel ordre économique international, allocution à l'occasion d'une table ronde sur ce thème par l'UNESCO (23-27 juin 1976) ; « Sciences et Techniques », octobre 1976. 1979 : La bête immonde (avec J.-C. Pecker), « Le Matin », 20 mars. 1979 : Appel à nos ministres (avec J.-C. Pecker), « Le Monde », 13 décembre. 1979 : Le flou, le ténébreux, l'irrationnel (avec J.-C. Pecker), « Le Monde », 14 septembre. 1980 : Education à la paix, Préface, in : Publ. UNESCO. 1981 : Le vrai danger, « Le Monde », 6 août 1981. 1982 : Nucléaire civil et militaire, « Le Monde », 1er juin 1982. 1982 : Les scientifiques face à la perspective d'holocauste nucléaire (texte inédit). Le titre de cette communication en résume seulement une partie : l'importance prise en astrophysique par l'analyse des situations hors ETL est devenue considérable, qu'il s'agisse des atmosphères stellaires, ou plus encore, des coïncidences fortuites de la formation des spectres d'émission nébulaires, ou des « masers » moléculaires interstellaires. Une autre partie de cet exposé souligne le rôle de Kastler dans son époque, et décrit sa personnalité généreuse à travers ses r

ERBB2 in Cat Mammary Neoplasias Disclosed a Positive Correlation between RNA and Protein Low Expression Levels: A Model for erbB-2 Negative Human Breast Cancer

Science.gov (United States)

Abreu, Rui M. V.; Bastos, Estela; Amorim, Irina; Gut, Ivo G.; Gärtner, Fátima; Chaves, Raquel

2013-01-01

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

CERES ERBE-like Instantaneous TOA Estimates (ES-8) in HDF (CER_ES8_Terra-FM1_Edition2)

Science.gov (United States)

Wielicki, Bruce A. (Principal Investigator)

The ES-8 archival data product contains a 24-hour, single-satellite, instantaneous view of scanner fluxes at the top-of-atmosphere (TOA) reduced from spacecraft altitude unfiltered radiances using Earth Radiation Budget Experiment (ERBE) scanner Inversion algorithms and the ERBE shortwave (SW) and longwave (LW) Angular Distribution Models (ADMs). The ES-8 also includes the total (TOT), SW, LW, and window (WN) channel radiometric data; SW, LW, and WN unfiltered radiance values; and the ERBE scene identification for each measurement. These data are organized according to the CERES 3.3-second scan into 6.6-second records. As long as there is one valid scanner measurement within a record, the ES-8 record will be generated. The following CERES ES8 data sets are currently available: CER_ES8_TRMM-PFM_Edition1 CER_ES8_TRMM-PFM_Edition2 CER_ES8_TRMM-PFM_Transient-Ops2 CER_ES8_Terra-FM1_Edition1 CER_ES8_Terra-FM2_Edition1 CER_ES8_Terra-FM1_Edition2 CER_ES8_Terra-FM2_Edition2 CER_ES8_Aqua-FM3_Edition1 CER_ES8_Aqua-FM4_Edition1 CER_ES8_Aqua-FM3_Edition2 CER_ES8_Aqua-FM4_Edition2 CER_ES8_Aqua-FM3_Edition1-CV CER_ES8_Aqua-FM4_Edition1-CV CER_ES8_Terra-FM1_Edition1-CV CER_ES8_Terra-FM1_Edition1-CV. [Location=GLOBAL] [Temporal_Coverage: Start_Date=1997-12-27; Stop_Date=2006-01-01] [Spatial_Coverage: Southernmost_Latitude=-90; Northernmost_Latitude=90; Westernmost_Longitude=-180; Easternmost_Longitude=180] [Data_Resolution: Temporal_Resolution=1 day; Temporal_Resolution_Range=Daily - < Weekly].

CERES ERBE-like Instantaneous TOA Estimates (ES-8) in HDF (CER_ES8_Terra-FM2_Edition1)

Science.gov (United States)

Wielicki, Bruce A. (Principal Investigator)

The ES-8 archival data product contains a 24-hour, single-satellite, instantaneous view of scanner fluxes at the top-of-atmosphere (TOA) reduced from spacecraft altitude unfiltered radiances using Earth Radiation Budget Experiment (ERBE) scanner Inversion algorithms and the ERBE shortwave (SW) and longwave (LW) Angular Distribution Models (ADMs). The ES-8 also includes the total (TOT), SW, LW, and window (WN) channel radiometric data; SW, LW, and WN unfiltered radiance values; and the ERBE scene identification for each measurement. These data are organized according to the CERES 3.3-second scan into 6.6-second records. As long as there is one valid scanner measurement within a record, the ES-8 record will be generated. The following CERES ES8 data sets are currently available: CER_ES8_TRMM-PFM_Edition1 CER_ES8_TRMM-PFM_Edition2 CER_ES8_TRMM-PFM_Transient-Ops2 CER_ES8_Terra-FM1_Edition1 CER_ES8_Terra-FM2_Edition1 CER_ES8_Terra-FM1_Edition2 CER_ES8_Terra-FM2_Edition2 CER_ES8_Aqua-FM3_Edition1 CER_ES8_Aqua-FM4_Edition1 CER_ES8_Aqua-FM3_Edition2 CER_ES8_Aqua-FM4_Edition2 CER_ES8_Aqua-FM3_Edition1-CV CER_ES8_Aqua-FM4_Edition1-CV CER_ES8_Terra-FM1_Edition1-CV CER_ES8_Terra-FM1_Edition1-CV. [Location=GLOBAL] [Temporal_Coverage: Start_Date=1997-12-27; Stop_Date=2005-11-01] [Spatial_Coverage: Southernmost_Latitude=-90; Northernmost_Latitude=90; Westernmost_Longitude=-180; Easternmost_Longitude=180] [Data_Resolution: Temporal_Resolution=1 day; Temporal_Resolution_Range=Daily - < Weekly].

CERES ERBE-like Instantaneous TOA Estimates (ES-8) in HDF (CER_ES8_Aqua-FM3_Edition2)

Science.gov (United States)

Wielicki, Bruce A. (Principal Investigator)

The ES-8 archival data product contains a 24-hour, single-satellite, instantaneous view of scanner fluxes at the top-of-atmosphere (TOA) reduced from spacecraft altitude unfiltered radiances using Earth Radiation Budget Experiment (ERBE) scanner Inversion algorithms and the ERBE shortwave (SW) and longwave (LW) Angular Distribution Models (ADMs). The ES-8 also includes the total (TOT), SW, LW, and window (WN) channel radiometric data; SW, LW, and WN unfiltered radiance values; and the ERBE scene identification for each measurement. These data are organized according to the CERES 3.3-second scan into 6.6-second records. As long as there is one valid scanner measurement within a record, the ES-8 record will be generated. The following CERES ES8 data sets are currently available: CER_ES8_TRMM-PFM_Edition1 CER_ES8_TRMM-PFM_Edition2 CER_ES8_TRMM-PFM_Transient-Ops2 CER_ES8_Terra-FM1_Edition1 CER_ES8_Terra-FM2_Edition1 CER_ES8_Terra-FM1_Edition2 CER_ES8_Terra-FM2_Edition2 CER_ES8_Aqua-FM3_Edition1 CER_ES8_Aqua-FM4_Edition1 CER_ES8_Aqua-FM3_Edition2 CER_ES8_Aqua-FM4_Edition2 CER_ES8_Aqua-FM3_Edition1-CV CER_ES8_Aqua-FM4_Edition1-CV CER_ES8_Terra-FM1_Edition1-CV CER_ES8_Terra-FM1_Edition1-CV. [Location=GLOBAL] [Temporal_Coverage: Start_Date=1997-12-27; Stop_Date=2005-12-31] [Spatial_Coverage: Southernmost_Latitude=-90; Northernmost_Latitude=90; Westernmost_Longitude=-180; Easternmost_Longitude=180] [Data_Resolution: Temporal_Resolution=1 day; Temporal_Resolution_Range=Daily - < Weekly].

Le contrôle de gestion environnementale d'une entreprise

OpenAIRE

Marquet-Pondeville, Sophie

2001-01-01

Dans cette recherche, nous étudions comment s’opère le contrôle de gestion environnementale. Cette problématique est abordée dans une perspective contingente et nous proposons un modèle théorique qui met en évidence l’impact de certaines variables sur les systèmes de contrôle de la gestion environnementale. Certains liens présents dans ce modèle sont discutés à travers une étude de cas.

Prognostic value of p53, c-ErbB2 and tunel data in upper urothelial carcinoma associated with Balkan nephropathy

Directory of Open Access Journals (Sweden)

Savin Marina

2014-01-01

Full Text Available A characteristic tumor suppressor protein 53 (p53 mutational profile of genotoxic action of aristolochic acid was identified in the upper urothelial carcinoma (UUTT associated with Balkan nephropathy (BEN. In the present study, we examined the prognostic value of tissue-based molecular markers in overall-survival (OS risk after surgical treatment of UUTT, adjusted for gender, age and urological characteristics in 32 patients with BEN. Immunohistochemical examination of p53, the proliferation cell nuclear antigen (PCNA, the human epidermal growth factor receptor 2 (c-ErbB2; also known as HER-2/neu proto-oncogene and the in situ terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL assay for apoptosis detection were used to examine serial tumor sections. The median OS-time was 60 months for UUTT operation; the mortality rate (18.7% was related to (new disease (reoccurrence or invasion in 12-216 months. High-grade (p=0.029, TUNEL>0.36%+ cells (p=0.010, and c-ErbB2+ cells (p=0.014 can define the risk of tumor invasion. Patients with Balkan nephropathy that develop UUTT at a stage greater than pT1 (with apoptosis TUNEL+ cells >0.36% and p53+ cells greater than 10% were at high risk of poor-OS after the tumor surgery (h(x=6.35; p=0.045. The obtained data present evidence for p53, cErbB2 and apoptosis deregulation, as a result of environmental toxin action. This is the first report of molecular biomarker linkage with OS for BEN-associated UUTT.

Mammary gland cancer in a colony of beagle dogs: Inheritance, and p53 ampersand erbB-2 expression

International Nuclear Information System (INIS)

Kelly, G.; Griffith, W.C.; Muggenburg, Tierney, L.A.; Lechner, J.F.; Hahn, F.F.

1994-01-01

One American woman in nine will be diagnosed with breast cancer in her lifetime. This somber statistic translates into 182,000 new diagnoses and 46,000 deaths per year. Efforts to decrease breast cancer mortality have focused on early detection and improved treatment. Such efforts would be facilitated by the identification of individuals predisposed to the disease. A family history of the disease can increase a woman's risk for developing breast cancer by two- to six-fold. Inheritance of this disease is consistent with at least one susceptibility locus on chromosome 17 (17q12-21) with incomplete penetrance. However, other mechanisms of inherited susceptibility also contribute to the high incidence of the disease. The purpose of the present study was to characterize familial pattern of mammary cancer development in the dog colony. In addition, the expression of the p53 tumor supressor gene and c-erbB2 (p185 erbB2 ) oncogene proteins, which are frequently altered in human breast cancer, were examined in dogs susceptible and resistant to mammary cancer

Le rôle des intervenants non gouvernementaux dans le ...

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

Ce projet servira à déterminer les facteurs stratégiques et réglementaires qui ont contribué ou nui aux efforts visant à permettre aux fournisseurs non gouvernementaux de participer au renforcement des systèmes de santé. Le rôle des fournisseurs de ... Climate Change and Water Adaptation Options. The impacts of climate ...

Le stéréotype dans le roman policier

Directory of Open Access Journals (Sweden)

Marion François

2009-12-01

Full Text Available Le roman policier offre à l’étude du stéréotype une grande variété de redondances, lexicales et structurelles, qui permettent d’éclairer le concept même de genre, en fait issu du constat de stéréotypie. Il est également manifeste que contrairement aux idées reçues, les clichés font du texte policier un texte littéraire, parce qu’ils naissent d’images associées, distinctes de la réalité, qui révèlent d’ailleurs le cheminement même de l’écriture. Par ailleurs ces images jouent un rôle fondamental dans le plaisir du lecteur, comme dans les contes de fées de notre enfance. Les clichés ouvrent la porte des fantasmes : le stéréotype rejoignant l’archétype, les clichés policiers réactivent de nombreux mythes, le texte évoquant l’Autre Scène. Le constat de stéréotypie provoque l’écriture, en particulier parodique, et stimule le renouvellement et l’essaimage des clichés dans toutes sortes de textes, qui bénéficieront de la présence du déjà-lu, laquelle donne au lecteur une assise pour affronter l’inconnu et une expérience pour apprécier la nouveauté.

Fractures obstétricales lors des césariennes au CHU de Yopougon ...

African Journals Online (AJOL)

Les lésions associées étaient représentées par six paralysies du plexus brachial (POPB) type Duchenne Erb. Le traitement était orthopédique dans tous les cas avec un bon pronostic. Notre étude montre que la césarienne n'annule pas le risque de fracture obstétricale. Une meilleure maîtrise de la dynamique obstétricale ...

p53, erbB-2 and K-ras gene alterations are rare in spontaneous and plutonium-239-induced canine lung neoplasia

International Nuclear Information System (INIS)

Tierney, L.A.; Hahn, F.F.; Lechner, J.F.

1996-01-01

Inhalation of high-linear energy transfer radiation in the form of radon progeny is a suspected cause of human lung cancer. To gain insight into the types of genetic derangements caused by this type of radiation, lung tumors from beagle dogs exposed to 239 PuO 2 and those arising in animals with no known carcinogen exposure were examined for evidence of aberrations in genes known to be altered in lung tumors. Altered expression of the p53 tumor suppressor gene and proto-oncogene erbB-2 proteins (p185 erbB2 ) was evaluated by immunohistochemical analysis of 117 tumors representing different histological types in exposed (n = 80) and unexposed (n = 37) animals. Twenty-eight tumors were analyzed for K-ras proto-oncogene mutations by polymerase chain reaction amplification and direct sequencing. Fourteen percent (16/116) of all lung neoplasms showed elevated nuclear accumulation of p53 protein. Regardless of exposure history, adenosquamous and squamous cell cancers comprised 94% of all tumors with p53 abnormalities. Eighteen percent (21/117) of all tumors had evidence of erbB-2 protein overexpression. K-ras mutations were not detected in codons 12, 13 or 61 of tumors from unexposed (n = 9) or plutonium-exposed dogs (n = 19). These data indicate that p53 and K-ras gene abnormalities as a result of missense mutation are infrequent events in spontaneous and 239 PuO 2 -induced lung neoplasia in this colony of beagle dogs. Alternative mechanisms of gene alteration may be involved in canine pulmonary carcinogenesis. 45 refs., 3 figs., 2 tabs

Increased level of phosphorylated akt measured by chemiluminescence-linked immunosorbent assay is a predictor of poor prognosis in primary breast cancer overexpressing ErbB-2

International Nuclear Information System (INIS)

Cicenas, Jonas; Urban, Patrick; Vuaroqueaux, Vincent; Labuhn, Martin; Küng, Willy; Wight, Edward; Mayhew, Mark; Eppenberger, Urs; Eppenberger-Castori, Serenella

2005-01-01

Akt1, Akt2 and Akt3 kinases are downstream components of phosphoinositol 3-kinase derived signals from receptor tyrosine kinases, which influence cell growth, proliferation and survival. Akt2 overexpression and amplification have been described in breast, ovarian and pancreatic cancers. The present study was designed to investigate the prognostic significance of activated Akt in primary breast cancer and its association with other tumour biomarkers. Using a two-site chemiluminescence-linked immunosorbent assay, we measured the quantitative expression levels of total phosphorylated (P-S473) Akt (Akt1/Akt2/Akt3) on cytosol fractions obtained from fresh frozen tissue samples of 156 primary breast cancer patients. Akt phosphorylation was not associated with nodal status or ErbB-2 protein expression levels. High levels of phosphorylated Akt correlated (P < 0.01) with poor prognosis, and the significance of this correlation increased (P < 0.001) in the subset of patients with ErbB-2 overexpressing tumours. In addition, phosphorylated Akt was found to be associated with mRNA expression levels of several proliferation markers (e.g. thymidylate synthase), measured using quantitative real-time RT-PCR. Our findings demonstrate that, in breast cancer patients, Akt activation is associated with tumour proliferation and poor prognosis, particularly in the subset of patients with ErbB2-overexpressing tumours

CERES ERBE-like Instantaneous TOA Estimates (ES-8) in HDF (CER_ES8_Aqua-FM4_Edition1-CV)

Science.gov (United States)

Wielicki, Bruce A. (Principal Investigator)

The ES-8 archival data product contains a 24-hour, single-satellite, instantaneous view of scanner fluxes at the top-of-atmosphere (TOA) reduced from spacecraft altitude unfiltered radiances using Earth Radiation Budget Experiment (ERBE) scanner Inversion algorithms and the ERBE shortwave (SW) and longwave (LW) Angular Distribution Models (ADMs). The ES-8 also includes the total (TOT), SW, LW, and window (WN) channel radiometric data; SW, LW, and WN unfiltered radiance values; and the ERBE scene identification for each measurement. These data are organized according to the CERES 3.3-second scan into 6.6-second records. As long as there is one valid scanner measurement within a record, the ES-8 record will be generated. The following CERES ES8 data sets are currently available: CER_ES8_TRMM-PFM_Edition1 CER_ES8_TRMM-PFM_Edition2 CER_ES8_TRMM-PFM_Transient-Ops2 CER_ES8_Terra-FM1_Edition1 CER_ES8_Terra-FM2_Edition1 CER_ES8_Terra-FM1_Edition2 CER_ES8_Terra-FM2_Edition2 CER_ES8_Aqua-FM3_Edition1 CER_ES8_Aqua-FM4_Edition1 CER_ES8_Aqua-FM3_Edition2 CER_ES8_Aqua-FM4_Edition2 CER_ES8_Aqua-FM3_Edition1-CV CER_ES8_Aqua-FM4_Edition1-CV CER_ES8_Terra-FM1_Edition1-CV CER_ES8_Terra-FM1_Edition1-CV. [Location=GLOBAL] [Temporal_Coverage: Start_Date=1997-12-27; Stop_Date=2005-03-29] [Spatial_Coverage: Southernmost_Latitude=-90; Northernmost_Latitude=90; Westernmost_Longitude=-180; Easternmost_Longitude=180] [Data_Resolution: Temporal_Resolution=1 day; Temporal_Resolution_Range=Daily - < Weekly].

CERES ERBE-like Instantaneous TOA Estimates (ES-8) in HDF (CER_ES8_Terra-FM1_Edition1-CV)

Science.gov (United States)

Wielicki, Bruce A. (Principal Investigator)

The ES-8 archival data product contains a 24-hour, single-satellite, instantaneous view of scanner fluxes at the top-of-atmosphere (TOA) reduced from spacecraft altitude unfiltered radiances using Earth Radiation Budget Experiment (ERBE) scanner Inversion algorithms and the ERBE shortwave (SW) and longwave (LW) Angular Distribution Models (ADMs). The ES-8 also includes the total (TOT), SW, LW, and window (WN) channel radiometric data; SW, LW, and WN unfiltered radiance values; and the ERBE scene identification for each measurement. These data are organized according to the CERES 3.3-second scan into 6.6-second records. As long as there is one valid scanner measurement within a record, the ES-8 record will be generated. The following CERES ES8 data sets are currently available: CER_ES8_TRMM-PFM_Edition1 CER_ES8_TRMM-PFM_Edition2 CER_ES8_TRMM-PFM_Transient-Ops2 CER_ES8_Terra-FM1_Edition1 CER_ES8_Terra-FM2_Edition1 CER_ES8_Terra-FM1_Edition2 CER_ES8_Terra-FM2_Edition2 CER_ES8_Aqua-FM3_Edition1 CER_ES8_Aqua-FM4_Edition1 CER_ES8_Aqua-FM3_Edition2 CER_ES8_Aqua-FM4_Edition2 CER_ES8_Aqua-FM3_Edition1-CV CER_ES8_Aqua-FM4_Edition1-CV CER_ES8_Terra-FM1_Edition1-CV CER_ES8_Terra-FM1_Edition1-CV. [Location=GLOBAL] [Temporal_Coverage: Start_Date=1997-12-27; Stop_Date=2006-09-30] [Spatial_Coverage: Southernmost_Latitude=-90; Northernmost_Latitude=90; Westernmost_Longitude=-180; Easternmost_Longitude=180] [Data_Resolution: Temporal_Resolution=1 day; Temporal_Resolution_Range=Daily - < Weekly].

pour le trimestre qui a pris fin le 30 juin 2015

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

Office 2004 Test Drive User

30 juin 2015 ... Le CRDI finance des travaux de recherche appliquée ... recherches pour le développement international (le Centre) et de ..... voie de développement et sur la mise en oeuvre des connaissances scientifiques, techniques et autres en .... Les accords expirent à des dates différentes, et le dernier prend fin en.

Le CRDI et la lutte contre le paludisme | CRDI - Centre de ...

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

22 juil. 2011 ... D'autres interventions luttent également contre le paludisme, notamment les moustiquaires imprégnées d'insecticide et les médicaments visant à prévenir le ... Le CRDI appuie le GCRAI depuis les années 1970 et participe avec SIMA au financement de la recherche sur les interactions complexes entre ...

Le livre sur le livre traité de documentation

CERN Document Server

Otlet, Paul

2015-01-01

Paul Otlet est considéré comme le père des sciences de l'information. Ouvrage fondateur et fondamental, le Traité de documentation. Le livre sur le livre (1934) est l'aboutissement de son travail inlassable pour rassembler, classer et partager les connaissances. Otlet y propose une remarquable synthèse du savoir sur le livre et le document en même temps qu'il anticipe Internet et l'hypertexte. La réédition du Traité de documentation, 70 ans après la disparition de son auteur, coïncide avec la réouverture du Mundaneum à Mons, où le fabuleux héritage documentaire légué par Paul Otlet et Henri La Fontaine est conservé. « Ici, la table de travail n'est plus chargée d'aucun livre. À leur place se dresse un écran et à portée un téléphone. Là-bas, au loin, dans un édifice immense, sont tous les livres et tous les renseignements. De là, on fait apparaître sur l'écran la page à lire pour connaître la réponse aux questions posées par téléphone. » Préfaces de Benoît Peeters (éc...

miR-125b acts as a tumor suppressor in chondrosarcoma cells by the sensitization to doxorubicin through direct targeting the ErbB2-regulated glucose metabolism.

Science.gov (United States)

Tang, Xian-ye; Zheng, Wei; Ding, Min; Guo, Kai-jin; Yuan, Feng; Feng, Hu; Deng, Bin; Sun, Wei; Hou, Yang; Gao, Lu

2016-01-01

Chondrosarcoma is the second most common type of primary bone malignancy in the United States after osteosarcoma. Surgical resections of these tumors are the only effective treatment to chondrosarcoma patients due to their resistance to conventional chemo- and radiotherapy. In this study, miR-125b was found to perform its tumor-suppressor function to inhibit glucose metabolism via the direct targeting of oncogene, ErbB2. We report miR-125b was downregulated in both chondrosarcoma patient samples and cell lines. The total 20 Asian chondrosarcoma patients showed significantly downregulated miR-125b expression compared with normal tissues. Meanwhile, miR-125 was downregulated in chondrosarcoma cells and doxorubicin resistant cells. Overexpression of miR-125 enhanced the sensitivity of both parental and doxorubicin resistant cells to doxorubicin through direct targeting on the ErbB2-mediated upregulation of glycolysis in chondrosarcoma cells. Moreover, restoration of the expression of ErbB2 and glucose metabolic enzymes in miR-125 pretransfected cells recovered the susceptibility to doxorubicin. Our study will provide a novel aspect on the overcoming chemoresistance in human chondrosarcoma cells and may help in the development of therapeutic strategies for the treatments of patients.

Vitamin E analogs trigger apoptosis in HER2/erbB2-overexpressing breast cancer cells by signaling via the mitochondrial pathway

Czech Academy of Sciences Publication Activity Database

Wang, X.-F.; Witting, P. K.; Salvatore, B.A.; Neužil, Jiří

2005-01-01

Roč. 326, č. 4 (2005), s. 282-289 ISSN 0006-291X Institutional research plan: CEZ:AV0Z5052915; CEZ:AV0Z50520514 Keywords : vitamin E analogs * apoptosis * ErbB2 Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.000, year: 2005

L’Association du personnel, le TREF, le Comité des Finances et le Conseil du CERN

CERN Multimedia

Staff Association

2016-01-01

L’Association du personnel, forte de son approche participative et consensuelle, recherche toujours le meilleur accord possible pour l’Organisation et son personnel. Pour ce faire, discussions et concertation avec la Direction, travail d’explication et de persuasion au TREF et ailleurs auprès des délégués des États membres sont nos principaux atouts. TREF (Tripartite Employment Conditions Forum), un Forum d’échanges, de discussions « L’objectif du Forum est d’améliorer le processus de prise de décision  en donnant aux personnes concernées la possibilité et le temps de comprendre pleinement la position de tous les participants. » (CERN/RTG/8) Le Forum tripartite sur les conditions d’emploi (TREF), créé par le Conseil du CERN en juin 1994, est composé de r...

INVESTIR DANS LE SAVOIR : le soutien que le CRDI consent à des ...

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

5 nov. 2010 ... ... 40 ans, le Cenre de recherches pour le développement international (CRDI), en plus d'appuyer des travaux de recherche dans l'ensemble des pays en développement, encourage des générations successives de jeunes chercheurs par l'entremise de son Programme de formation et de bourses (PFB).

Le nouveau modèle africain | IDRC - International Development ...

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

22 juil. 2011 ... L'annulation de la dette, un commerce plus équitable, davantage d'aide : voilà le plan d'action mondial dont on convient qu'il faut de toute urgence mettre en oeuvre en vue d'accélérer le développement en Afrique. Or, ce serait rater le bateau que de ne pas s'engager dans la voie tout autre que les ...

La lipogenèse chez le lapin. Importance pour le contrôle de la teneur en lipides de la viande

OpenAIRE

Gondret, Florence

1999-01-01

La teneur en lipides d’un tissu est la résultante de plusieurs flux métaboliques (dépôt, synthèse, utilisation). Cet article présente les principales caractéristiques de la synthèse des lipides chez le lapin, dans le muscle comparativement aux tissus adipeux visibles et au foie. Le potentiel de synthèse de novo exprimé par le muscle augmente avec l’âge de l’animal, en parallèle à l’accumulation des triglycérides dans les adipocytes intramusculaires. L’activité des enzymes qui fournissent le N...

The Predictive and Prognostic Significance of c-erb-B2, EGFR, PTEN, mTOR, PI3K, p27, and ERCC1 Expression in Hepatocellular Carcinoma

Science.gov (United States)

Bassullu, Nuray; Turkmen, Ilknur; Dayangac, Murat; Yagiz Korkmaz, Pinar; Yasar, Reyhan; Akyildiz, Murat; Yaprak, Onur; Tokat, Yaman; Yuzer, Yildiray; Bulbul Dogusoy, Gulen

2012-01-01

Background Hepatocellular carcinoma (HCC) is the fifth most common fatal cancer and an important healthcare problem worldwide. There are many studies describing the prognostic and predictive effects of epidermal growth factor receptor 2 (c-erb-B2) and epidermal growth factor receptor 1 (EGFR), transmembrane tyrosine kinases that influence cell growth and proliferation in many tumors. Objectives The current study aimed to investigate the expression levels of c-erb-B2, EGFR, PTEN, mTOR, PI3K, p27, and ERCC1 in hepatocellular carcinoma (HCC) and their correlation with other clinicopathologic features. Patients and Methods Fifty HCC cases were stained immunohistochemically with these markers. Correlations between the markers and clinicopathologic characteristics and survival rates were analyzed. Results No membranous c-erb-B2 staining was seen, whereas cytoplasmic positivity was present in 92% of HCC samples, membranous EGFR was observed in 40%, PI3K was found in all samples, and mTOR was seen in 30%, whereas reduced or absent PTEN expression was observed in 56% of samples and loss of p27 was seen in 92% of the cases. c-erb-B2 and mTOR overexpression, as well as reduced expression of p27, all correlated with multiple tumors (P = 0.041, P < 0.001, and P < 0.001, respectively). P27 loss, and mTOR and EGFR positivity were significantly correlated with AFP (P = 0.047, P = 0.004, and P = 0.008, respectively). Angiolymphatic invasion was more commonly seen in EGFR- and ERCC1-positive cases (P = 0.003 and P = 0.005). EGFR was also correlated with histological grade (P = 0.039). No significant correlations were found among PTEN , PI3K, and the clinicopathological parameters. Disease-free or overall survival rates showed significant differences among therapy modalities, AFP levels, angiolymphatic or lymph node invasions, and ERCC1 and p27 expression levels (P < 0.05). Conclusions c-erb-B2, EGFR, mTOR, ERCC1 overexpression levels, and loss of p27 may play roles in

Rapport financier trimestriel pour le trimestre qui a pris fin le 31

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

Office 2004 Test Drive User

31 déc. 2015 ... Le CRDI finance des travaux de recherche appliquée ... recherches pour le développement international (CRDI, le Centre) et ..... voie de développement et sur la mise en oeuvre des connaissances scientifiques, techniques et autres en .... Les accords expirent à des dates différentes, et le dernier prend fin.

Rapport financier trimestriel pour le trimestre qui a pris fin le 30

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

Office 2004 Test Drive User

30 sept. 2015 ... Le CRDI finance des travaux de recherche appliquée ... recherches pour le développement international (le Centre) et de ..... voie de développement et sur la mise en oeuvre des connaissances scientifiques, techniques et autres en .... Les accords expirent à des dates différentes, et le dernier prend fin en.

Le modèle spatial de la capitale allemande

Directory of Open Access Journals (Sweden)

Antoine Laporte

2013-06-01

Full Text Available En Allemagne, en 1999, le Chancelier fédéral et son gouvernement ont quitté Bonn pour Berlin. Ce transfert du pouvoir est accompagné de celui d’une grande partie de l’appareil d’État et de la haute administration, et des fonctions qui leur sont traditionnellement attribuées comme la presse, les lobbys ou encore la diplomatie. Le déplacement du statut de capitale effective de l’Allemagne de Bonn à Berlin est le résultat des évolutions géopolitiques d’un pays ayant recouvré son unité et sa pleine et entière souveraineté. Installer le pouvoir exécutif et législatif à Berlin était une démarche hautement symbolique, visant à normaliser la position de l’ancienne capitale de la RDA et du IIIe Reich comme véritable centre politique de l’Allemagne. Or le déplacement des institutions fédérales n’est pas qu’un acte symbolique. Il entraîne également à l’échelle intra-urbaine des dynamiques très concrètes sur le tissu urbain et participe à la mise en place de nouvelles centralités dans la ville. En effet, le statut de capitale d’État prédestine l’agglomération à la coprésence de nombreuses fonctions urbaines spécifiques plus ou moins directement liées à l’exercice ou à la symbolique du pouvoir.

Les femmes dans le secteur du travail domestique et le secteur ...

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

Ce projet vise à rectifier le tir en faisant la lumière sur les caractéristiques ... le secteur du travail domestique et dans le secteur bancaire modifient la nature du travail ... des sciences sociales, des sciences humaines, de la santé publique ou.

Le Conseil des gouverneurs | CRDI - Centre de recherches pour le ...

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

Le Conseil des gouverneurs guide le travail du CRDI en lui fournissant une orientation stratégique, en examinant ses activités et en approuvant ses budgets. Les gouverneurs – un maximum de 14 – sont nommés par le gouverneur en conseil du Canada pour un mandat d'au plus quatre ans, qui peut être reconduit. La Loi ...

Le FIVB annonce le financement de cinq autres projets | CRDI ...

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

10 avr. 2018 ... En partenariat avec la Fondation Bill et Melinda Gates et Affaires mondiales Canada, le CRDI est heureux d'annoncer la prochaine série de projets soutenus par le Fonds d'innovation en matière de vaccins pour le bétail (FIVB). À ce jour, 11 projets ont obtenu un financement total de 13,6 millions de CAD ...

Démocratie et le développement dans le monde arabe | IDRC ...

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

Le Rapport sur le développement humain dans le monde arabe 2002 souligne un " déficit en matière de libertés " fondamental dans le monde arabe se traduisant dans toute la région par des régimes autoritaires et la faiblesse de la démocratie. Cette subvention permettra aux chercheurs Samir Makdisi et Ibrahim Elbadawi ...

Le nouveau modèle africain | CRDI - Centre de recherches pour le ...

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

22 juil. 2011 ... Or, ce serait rater le bateau que de ne pas s'engager dans la voie tout autre que les Africains proposent maintenant — à savoir se défaire du syndrome de la dépendance qui afflige l'Afrique depuis des décennies. Le Canada et les autres pays riches du Nord reconnaissent généralement qu'ils ne peuvent ...

Le facteur humain et la sûreté de fonctionnement dans le ...

African Journals Online (AJOL)

Notre contribution porte sur le rôle fondamental du facteur humain dans le management intégré des risques d'une part et du rôle déterminant qu'il peut avoir à jouer pour que la sûreté de fonctionnement réponde à sa propriété d'autre part. Un rôle illustré à travers une analyse de risque dans un complexe de Gaz Naturel ...

Le corps sportif1

OpenAIRE

Brulé, Pierre

2015-01-01

Le nu et le cuit Si, pas plus que l’Auvergne, le monde grec antique n’a été le théâtre d’un quelconque « miracle », il n’a pas manqué, toutefois, de « distinctions » diverses, d’exceptions même, qui le singularisent absolument. Une, c’est la pédérastie. Quelle culture l’a autant valorisée, autant instrumentalisée, l’a autant érigée en modèle ? Nous n’en avons pas encore mesuré toutes les conséquences. La place inhabituelle que prend là et alors cette polyvalence rare de la libido masculine de...

Prognostic value of Laurén classification and c-erbB-2 oncogene overexpression in adenocarcinoma of the esophagus and gastroesophageal junction

NARCIS (Netherlands)

Polkowski, W.; van Sandick, J. W.; Offerhaus, G. J.; ten Kate, F. J.; Mulder, J.; Obertop, H.; van Lanschot, J. J.

1999-01-01

The prognostic value of the Laurén classification and of c-erbB-2 oncogene overexpression has been described for gastric cancer. The aim of this study was to investigate the clinical significance of these factors in adenocarcinoma of the esophagus and/or gastroesophageal junction (GEJ). Forty-one

Hyperloop : le droit et le devoir de douter...

OpenAIRE

Crozet , Yves

2016-01-01

National audience; C’est comme si c’était fait ! Les journaux les plus sérieux (Les Echos) nous annoncent que le premier test du prototype Hyperloop dans le désert du Nevada est un succès. Le projet futuriste d’Elon Musk se concrétise. Un véhicule terrestre de transport collectif va bientôt se déplacer à plus de 1000 km/h entre San Francisco et Los Angeles. Comme pour donner du crédit à cette information, la SNCF, via sa filiale SYSTRA va devenir partenaire du projet. Déjà les journaux de Pro...

LE LIEN ENTRE FINANCE ET ECONOMIE ISLAMIQUES VIA LE MODELE PRINCIPIEL "ZR"

OpenAIRE

BELABES, ABDERRAZAK

2010-01-01

A l'heure où certains évoquent l'intégration de la finance islamique à la finance globale, et d'autres rattachent la finance islamique à des thèmes en vogue telles que la finance éthique, la finance participative ou la finance socialement responsable, le présent papier explore le lien entre finance et économie islamiques à partir du modèle principiel "ZR", c’est-à-dire "Zakât" et "Ribâ". Ce modèle montre que les principes invariants de Zakât et Ribâ jouent un rôle central dans l’établissement...

Le Kenya nomme le titulaire de sa première chaire de recherche

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

14 avr. 2016 ... De concert avec le CRDI, la National Commission for Science, Technology and Innovation (NACOSTI) du Kenya a inauguré sa première chaire de recherche à Nairobi, le 31 mars 2015. Le professeur Fabian Omoding Esamai, qui dirige actuellement le College of Health Sciences de la Moi University, a été ...

pour le trimestre qui a pris fin le 31 décembre 2014

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

Office 2004 Test Drive User

31 déc. 2014 ... Le CRDI finance des travaux de recherche appliquée ... recherches pour le développement international (le Centre) et de ...... voie de développement et sur la mise en oeuvre des connaissances scientifiques, techniques et autres en vue .... Les accords expirent à des dates différentes, et le dernier prend fin.

Le cru, le cuit et le pourri dans _Le vice-consul_ de Marguerite Duras

Directory of Open Access Journals (Sweden)

Hélène Caron

2011-05-01

Full Text Available Bien que plusieurs articles critiques aient déjà avancé de nouvelles perspectives sur le texte Le Vice-Consul (LVC de Marguerite Duras, l’analyse de la représentation de la nourriture dans ce roman n’a fait l’objet d’aucune étude. Cet article tente donc de combler cette lacune en proposant d’analyser les images du cru et du cuit, images qui se rejoignent sous les notions du pourri et de l’abject, tout en offrant quelques interprétations de l’un des passages critiques du roman où la folle mendiante croque la tête d’un poisson vivant.

Dicty_cDB: Contig-U05153-1 [Dicty_cDB

Lifescience Database Archive (English)

Full Text Available inalis hermaphrodit... 46 1.5 1 ( EY498541 ) CBBP4184.rev CBBP Hirudo medicinalis h...ermaphrodit... 46 1.5 1 ( EY488990 ) CBBP16769.rev CBBP Hirudo medicinalis hermaphrodi... 46 1.5 1 ( AP00806... Homo sapiens chromosome 19 clone RP11-330I7 map 1... 46 1.5 1 ( EY498542 ) CBBP4184.fwd CBBP Hirudo medic

Le Peer to Peer: Vers un Nouveau Modèle de Civilization

Directory of Open Access Journals (Sweden)

Michel Bauwens

2006-06-01

Full Text Available Le « peer to peer » est la dynamique intersubjective caractéristique des réseaux distribués. Le but de cet essai est de montrer qu'il s'agit d'une véritable nouvelle forme d’organisation sociale, apte à produire et échanger des biens, à créer de la valeur. Celle-ci est la conséquence d'un nouvel imaginaire social, et possède le potentiel de devenir le pilier d'un nouveau mode d'économie politique, voire d'un nouveau type de civilisation. Pour cela, nous allons d'abord définir le P2P, décrire en bref ces manifestations, et le différencier d'autres modalités d'échange intersubjectif tel que le marché, la hiérarchie, l'économie du don.Comme principale modalité P2P nous distinguons: Les processus de production P2P, comme troisième mode de production, qui n'est ni géré par un mode hiérarchique ou par l'état, ni répondant à des impératifs de profit ou qui sont modulés par le biais des prix. Les processus de gouvernance P2P, qui gouverne ces processus de production. Les formes de propriété P2P, qui sont destine a empecher l’appropriation prive de cette production pour le commun.Afin d’examiner les characteristiques de cette nouvelle dynamique sociale, nous utilisons la typologie intersubjective de l’anthropologue Alan Page Fisque, qui distingue: 1. l'échange égalitaire (Equality Matching, c..a.d l’economie du don. 2. La relation d’autorité (Authority Ranking tel qu’elle s’exprime dans le mode hierarchique. 3. le marché (Market Pricing. 4. la participation commune (Communal Shareholding.En conclusion, nous examinons les possibilites d’expansion de ce nouveau mode sociale et son insertion dans l’economie capitaliste, en nous nous posons la question: le P2P peut-il etre concu comme alternative sociale et economique aux modeles existants.

Le « modèle germanique » Français

OpenAIRE

Lefebvre , Armelle

2009-01-01

Resume Le concept d?Allemagne permet de reveler, selon une approche , l?ampleur des desaccords ayant preside a la definition du concept d?Etat en France. De ce dernier, l?on aborde divers emplois qu?illustrent des modeles d?Etat. Le opere ainsi dans un debat qui est le creuset de la connaissance politique moderne, avec ses apories: celles de la souverainete externe, de l?ordre interetatique, de la confederation. L?article expose alo...

Los Dioramas de Le Corbusier = Le Corbusier's Dioramas

Directory of Open Access Journals (Sweden)

José Ramón Alonso Pereira

2013-10-01

Full Text Available ResumenLe Corbusier simboliza el urbanismo moderno racional, cuyo esfuerzo riguroso de planificación exige un esfuerzo paralelo de comprensión. Se opone a ese urbanismo contemporáneo que quiere percibir y disfrutar la ciudad sensiblemente. Sentimiento y razón, sin embargo, no son opuestos y Le Corbusier nos dio en su momento las claves para intentar una síntesis, uniéndolos de modo singular por medio de sus ‘boîte à miracles’ o ‘cajas mágicas’: esos "espectáculos arquitectónicos de síntesis" que definiría en el Ciam de 1951. Pretendemos aproximarnos aquí a la primera de esos ‘espectáculos’: el ‘diorama’, viéndolo como estrategia corbuseriana de mediación entre lo racional y lo sensible en la ciudad moderna y contemporánea.Palabras claveLe Corbusier, diorama, Ville Contemporaine, Plan Voisin, Plan MaciáAbstractLe Corbusier symbolizes the modern rational urbanism, whose rigorous effort of town planning demands a parallel effort of comprehension. It opposes to these contemporary urbanism that wish to perceive and to enjoy cities in a sensible way. Nevertheless, sentiment and reason are not adverses and Le Corbusier gives us at his  moment keys to intent a synthesis, joined them in a singular way by means of his ‘boîtes à miracles’ or ‘magic boxes’: those "architectural spectacles of synthesis" that he defined in 1951 Ciam. Here we try to approach to the first of those ‘spectacles’: the ‘diorama’, considering it as a corbusean strategy of mediation between rational and sensible in modern and contemporary city.Key wordsLe Corbusier, diorama, Ville Contemporaine, Plan Voisin, Plan Maciá.

Rapport financier trimestriel pour le trimestre qui a pris fin le 30

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

Sophie Comeau

30 sept. 2011 ... politiques, de chercheurs et de collectivités de par le monde. ..... Financement : le CRDI est visé par l'Examen stratégique et ... Le Conseil des gouverneurs a amorcé la planification du recrutement du nouveau président.

Le Sanskrit

CERN Document Server

Balbir, Nalini

2013-01-01

Cet ouvrage est destiné à tous ceux qui souhaitent se mettre ou se remettre à l'étude du sanskrit et ne peuvent y consacrer que quelques minutes par jour. En suivant le principe de la méthode quotidienne Assimil, vous acquerrez progressivement le vocabulaire et la grammaire de base qui sont nécessaires à la lecture des textes de la littérature sanskrite classique. Vous trouverez dans cette méthode une approche vivante de la langue et de la culture sanskrite classique à travers des textes d'abord adaptés pour le débutant puis authentiques. En quelques mois, vous manierez la langue sans efforts ni hésitation, de manière très naturelle. Les enregistrements reprennent l'intégralité des textes en sanskrit des leçons et des exercices de traduction du livre. Ils sont interprétés, à un rythme progressif, par des locuteurs natifs professionnels.

A Novel Screen for Suppressors of Breast Tumor Cell Growth Using an Oriented Random Peptide Library Method to Identify Inhibitors of the ErbB2 Tyrosine Kinase

National Research Council Canada - National Science Library

Carraway, Kermit

1998-01-01

.... To identify potential antagonists, the extracellular ligand binding domain of the ErbB2 is immobilized on a column support, and used to affinity purify cyclic peptides from oriented random peptide libraries...

A Novel Screen for Suppressors of Breast Tumor Cell Growth Using an Oriented Random Peptide Library Method to Identify Inhibitors of the ErbB2 Tyrosine Kinase

National Research Council Canada - National Science Library

Carraway, Kermit

1999-01-01

.... To identify potential antagonists, the extracellular ligand binding domain of the ErbB2 is immobilized on a column support, and used to affinity purify cyclic peptides from oriented random peptide libraries...

De quoi le genre est-il le nom ?

OpenAIRE

Andrieu, Bernard

2013-01-01

Cette note de lecture présente une courte évolution des travaux sur le genre sous l’angle du rapport au corps en démontrant comment la dénaturalisation du corps et du sexe biologique a conduit à une description culturaliste des fonctions individuelles et des rôles sociaux. Si le genre dénaturalise le corps c’est en refusant toute référence au sexe ou à la sexualité en tant qu’ils seraient des données naturelles. Depuis son apparition en 1947, sous la plume de John Money, psychologue chargé du...

Le modèle fédéral dans le sport français, un principe fondateur dépassé ?

Directory of Open Access Journals (Sweden)

Béatrice Barbusse

2009-06-01

Full Text Available Dans le sport français, le fédéralisme s’est installé comme une évidence institutionnelle dès la fin du 19e siècle et le début du 20e siècle dans un pays qui pourtant ne se pense pas fédéral. En outre, si son apparition est liée à l’émergence du sport comme nouvelle pratique sociale à côté d’autres pratiques physiques plus traditionnelles, il s’est rapidement imposé comme la pierre angulaire de l’ordre sportif français. Près d’un siècle plus tard, son monopole institutionnel est bousculé voire «concurrencé». Ces constats d’ensemble nous amènent à nous interroger sur les raisons pour lesquelles le sport a épousé le modèle fédéral dans un pays non fédéral, mais aussi sur ses limites actuelles. Est-il encore le modèle approprié aux circonstances contemporaines ? A-t-il toujours sa place dans le système de gouvernance du sport ? Ou bien, a contrario, reste-t-il le dernier rempart légitime face aux excès du sport contemporain (dopage, violence, corruptions, déficits… ? À partir d’une approche socio-historique, il s’est agi dans cet article de reconstruire le fil de la généalogie du fédéralisme sportif tout en s’interrogeant sur ses perspectives. Au delà de la question du fédéralisme, c’est bien celle de la gouvernance du sport contemporain qui est posée.

Le modèle judiciaire libéral mis à l’épreuve : la surveillance des juges sous le Directoire

OpenAIRE

Berger, Emmanuel

2007-01-01

La justice du Directoire est principalement identifiée aux différentes violations infligées par le gouvernement afin de contrôler le pouvoir judiciaire et durcir la répression criminelle. Cette représentation est, en réalité, partiale. L’auteur tente de le prouver à travers l’analyse d’un aspect essentiel du système judiciaire directorial : la surveillance des juges. L’étude des normes et des pratiques montre que le mode de surveillance établi par le code des délits et des peines respecte la ...

Rôle des universités dans le renforcement des technologies de l ...

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

Rôle des universités dans le renforcement des technologies de l'information et de la communication au service du développement (TIC-D) en Asie. Jusqu'à maintenant, les efforts déployés dans le secteur de l'enseignement supérieur ont surtout été axés sur le téléapprentissage, l'apprentissage électronique et différentes ...

Le Mouvement Social

OpenAIRE

FRIDENSON, Patrick

2003-01-01

J'ai la faiblesse d'affirmer que parmi les revues françaises d'histoire Le Mouvement Social est la revue qui a publié le plus d'articles et de comptes rendus en matière d'histoire des femmes et du gender. Chacun peut le vérifier grâce à nos pages Web sur le site Internet du Dictionnaire créé par Jean Maitron. Elles comportent la table des matières complète de la revue depuis sa fondation en 1960. Notre rédaction est extrêmement fière de ce résultat. Mais elle reconnaît qu'il a été difficile à...

Le faussaire roman

CERN Document Server

D'Anna, Gianfranco

2016-01-01

À l'aube du XXIe siècle, le monde de la science est sur le point de vivre une révolution. Le jeune physicien allemand Albert Hendrick Thebell, des célèbres laboratoires de recherche B-Labs, à Summit, dans le New Jersey, publie, dans les plus grandes revues scientifiques internationales, une série d'articles dans lesquels il prétend avoir obtenu des résultats extraordinaires qui pourraient révolutionner les bases mêmes de la technologie. Rapidement, la communauté scientifique puis les médias saluent en lui un futur prix Nobel; on compare même son génie à celui d'Albert Einstein. Le progrès scientifique semble avoir franchi une étape décisive, susceptible d'amener un futur meilleur. Mais ces découvertes sont-elles authentiques ? Car pendant ce temps, dans les mêmeslaboratoires, des voix s'élèvent pour contester non seulement les théories de Thebell mais aussi la légitimité même de ses expériences ; certains le soupçonnent d'avoir combiné la plus grande fraude scientifique de tous l...

Le rôle du pharmacien dans la fécondation in vitro

OpenAIRE

Hannoun , Odélia

2017-01-01

La procréation médicalement assistée regroupe plusieurs techniques venant en aide aux couples ayant des difficultés à concevoir. Environ 15% des couples en age de procréer consultent pour une difficulté à concevoir. Ce véritable problème de société nous incite à réfléchir sur le role que tient le pharmacien en tant que professionnel de santé dans le parcours de fécondation in vitro. Le pharmacien développe une relation étroite avec les patients au comptoir. Il est la pour expliquer le traitem...

Le boson et le chapeau mexicain un nouveau grand récit de l'univers

CERN Document Server

Cohen-Tannoudji, Gilles

2013-01-01

Le boson ? C'est l'ultime particule élémentaire prédite par la théorie de l'infiniment petit, qui manquait encore et dont la découverte, grâce au grand collisionneur de hadrons du CERN, a été annoncée au monde entier le 4 juillet 2012. Postulée en 1964 par Robert Brout, François Englert et Peter Higgs, elle explique que le photon - particule qui transmet la force électromagnétique - n'a pas de masse, à l'encontre de celles véhiculant la force faible. Une telle dissymétrie était a priori incompatible avec la symétrie fondamentale, dite «de jauge», sur laquelle est fondé le modèle standard de la physique des particules. Le chapeau mexicain ? C'est le mécanisme grâce auquel le boson rend compte, en préservant les acquis du modèle standard, de l'origine des masses des particules élémentaires. Le boson et le chapeau mexicain se placent à la croisée - retracée par les deux auteurs en dialogue avec François Englert - des chemins de l'évolution des théories de l'astrophysique contemp...

Activation of MAPK overrides the termination of myelin growth and replaces Nrg1/ErbB3 signals during Schwann cell development and myelination

NARCIS (Netherlands)

M.E. Sheean (Maria); E. McShane (Erik); C. Cheret (Cyril); J. Walcher (Jan); T. Müller (Thomas); A. Wulf-Goldenberg (Annika); S. Hoelper (Soraya); A.N. Garratt (Alistair); M. Krüger (Markus); K. Rajewsky (Klaus); D.N. Meijer (Dies); W. Birchmeier (Walter); G.R. Lewin (Gary); M. Selbach (Matthias); C. Birchmeier (Carmen)

2014-01-01

textabstractMyelination depends on the synthesis of large amounts of myelin transcripts and proteins and is controlled by Nrg1/ErbB/Shp2 signaling. We developed a novel pulse labeling strategy based on stable isotope labeling with amino acids in cell culture (SILAC) to measure the dynamics of myelin

Entre les violences conjugales et le harcèlement moral : le stalking .

Directory of Open Access Journals (Sweden)

Nicolas Desurmont

2007-09-01

Full Text Available Ce livre de la criminologue Murielle Anteo est le premier publié en langue française sur le stalking si l’on excepte les travaux encore inédits de Virginie Léon (2004. Comme le rappelle l’auteure, le terme est emprunté à l’anglais to stalk (hanter, rôder, et désigne un comportement menaçant, initié par un individu dont l’objectif conscient ou inconscient est l’objectivation de sa victime à des fins de domination. L’agression prend différentes formes : ...

Le jeu de la création : Le mangeur (2005) de Ying Chen

OpenAIRE

Nicole Dunham

2013-01-01

Le théoricien James Hans définit le jeu comme une déconstruction structurante, un processus de perpétuelle remise en question. Dans Le Mangeur (2005) de Ying Chen, la narratrice revit un épisode d’une de ses vies passées où elle meurt mangée, avalée, par son père, descendant dans le « tunnel » du ventre de ce dernier. Cependant, suite à cet événement, elle se retrouve dans un autre espace-temps où elle rencontre son mari, A.. Une équivalence s’établit dans le roman entre les éléments suivants...

A holistic approach to the management of Erb's palsy

Science.gov (United States)

Srilakshmi, Dasari; Chaganti, Sreelakshmi

2013-01-01

A 4.5-month-old female baby, presenting with complete paralysis of right upper limb with typical waiter's tip deformity, diagnosed as Erb's palsy was brought to Sri Ganapati Sachchidananda Hospital. Patient was treated with an integrated approach of physiotherapy and Ayurvedic treatment with an intention of aiding faster recovery of the patient to lead a near normal life. As per Ayurvedic classics, this condition can be correlated to Ekangavata (Vata effecting any one part of the body), which is Apatarpana in nature (diseases with deprived growth of body tissue). Hence, the choice of treatment is Santarpana Chikitsa (nourishing treatment). Santarpana Bahyopakramas (nourishing external treatment modalities) such as Ashwagandhabalalakshadi Taila (Ayurvedic medicated oil) Abhyanga (oleation therapy) and Shastikashali Anna Lepa (application of processed rice paste) were administered along with electrical stimulation (physiotherapy modality), both galvanic and faradic current in three sessions. Appreciable results were observed in the form of reduction of disparity in length and mid-arm circumference of right upper limb compared to unaffected left upper limb and the muscle power too improved from zero to four, facilitating patient to near normal movement. PMID:24459391

Le CRDI en Colombie

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

Le CRDI appuie la recherche en Colombie dans des domaines tels ... Le CRDI a soutenu des activités de longue haleine qui ont eu pour ... Des travaux subventionnés par le CRDI ont aidé une fondation à intégrer Internet à son programme ...

La construction de la matière le modèle Standard

CERN Document Server

Léon, Jacques

2016-01-01

Qu'est-ce que la matière ? Voilà une question à laquelle il pourrait sembler facile de répondre car il n'est rien de plus concret que la matière. Et pourtant, la réponse qu'en donne la physique contemporaine est pour le moins déconcertante ! Le concept-même de particules, briques élémentaires de la matière, s'est volatilisé, dissout dans des objets mathématiques abstraits et abscons pour les non-initiés. Plus nos théories sont précises et plus l'image qu'elles nous renvoient est insaisissable. En un siècle, la représentation des particules s'est métamorphosée en nuages de probabilité portés par des champs quantiques régis par des symétries confinées dans des espaces abstraits. Mais dans un même temps, nous avons réussi le tour de force d'expliquer toute cette complexité avec seulement 16 particules… et une seule théorie, véritable construction de notre conception de la matière : le modèle standard. Ce livre tente de guider le lecteur dans le dédale de la physique des particu...

Intelligence artificielle et agents collectifs : le modèle EUROSIM

Directory of Open Access Journals (Sweden)

Denise Pumain

2007-07-01

Full Text Available EUROSIM est un modèle multi-agents conçu pour simuler l’évolution à moyen terme du système des villes européennes. Les agents sont des entités collectives, les grandes villes caractérisées par leur taille et leur fonction dans le système des villes, et dont les interactions (échanges modulés par des relations de proximité ou de réseau déterminent la dynamique relative, tandis que la croissance d’ensemble dépend de l’innovation. Des outils d’analyse multiscalaire ont été développés afin d’interpréter les sorties du modèle et faciliter le calibrage.

ÉTUDE DE CAS — Cuba : Le logement et le capital humain à Cuba ...

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

10 janv. 2011 ... ÉTUDE DE CAS — Cuba : Le logement et le capital humain à Cuba ... Centre de recherches pour le développement international (CRDI) du Canada révèle ... Les ressources déjà limitées sont devenues encore plus rares. ... de l'Institut national pour l'hygiène, l'épidémiologie et la microbiologie (INHEM), ...

Le Rôle du langage de programmation dans la réalisation de code ...

African Journals Online (AJOL)

Le Rôle du langage de programmation dans la réalisation de code de qualité, les cas de Delphi et C++ Nous discutons dans ce papier le rôle du langage de programmation dans la production d'un code de qualité. La qualité d'un code peut être atteinte en respectant certains critères simples au niveau de la programmation ...

Gossip Girls : le rôle du potin dans quelques romans pour adolescentes

Directory of Open Access Journals (Sweden)

Daniela Di Cecco

2014-04-01

Full Text Available Cet article explore le rôle joué par le potin dans une sélection de romans anglophones publiés aux Etats-Unis et au Canada pour adolescentes et préadolescentes. Des études psychologiques et sociologiques récentes sur les agressions féminines et la façon dont les filles infligent de la peine aux autres filles de façon indirecte et voilée servent de cadre à notre analyse. Le fait que la violence physique soit considérée comme un comportement réservé aux garçons et donc inapproprié pour les filles, incite les adolescentes à agir autrement. Le potin devient parfois une arme pour marginaliser ou punir une fille, mais il peut aussi jouer un rôle positif au niveau de la cohésion d’une bande et de la solidarité entre filles.

205 Le Role de la Litterature dans le Developpement de la Nation ...

African Journals Online (AJOL)

Ike Odimegwu

du plaisir en même temps qu'il le moralise. Elle fait naître dans ses lecteurs ou dans son audience des .... développement de l'esprit>>(319)Par cette définition nous comprenons que le développement signale qu'il du progrès ... qu'elle est une œuvre de l'imagination qui aide l'homme à transcender le monde physique.

Rapport financier trimestriel pour le trimestre qui a pris fin le 30 juin ...

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

Sophie Comeau

30 juin 2017 ... Régi par la Loi sur le Centre de recherches pour le développement international ... des retombées; forme des leaders dans les secteurs de l'administration .... Au cours de la période de trois mois qui a pris fin le 30 juin 2017, ...

Le jeu de la création : Le mangeur (2005 de Ying Chen

Directory of Open Access Journals (Sweden)

Nicole Dunham

2013-11-01

Full Text Available Le théoricien James Hans définit le jeu comme une déconstruction structurante, un processus de perpétuelle remise en question. Dans Le Mangeur (2005 de Ying Chen, la narratrice revit un épisode d’une de ses vies passées où elle meurt mangée, avalée, par son père, descendant dans le « tunnel » du ventre de ce dernier. Cependant, suite à cet événement, elle se retrouve dans un autre espace-temps où elle rencontre son mari, A.. Une équivalence s’établit dans le roman entre les éléments suivants : le ventre du père, les tableaux peints par ce dernier et l’espace-temps de A., et la fenêtre. Ces éléments deviennent des aires de jeu, remettant en question les concepts de l’intérieur et de l’extérieur et du créateur et de l’œuvre. En nous servant du texte « Le Tunnel » écrit par Ying Chen, nous démontrerons que cette notion du jeu s’applique également à l’ensemble de son œuvre.

Le facteur humain et la sûreté de fonctionnement dans le ...

African Journals Online (AJOL)

Elle permettait d'optimiser le couple « performance-coût », en identifiant, évaluant et maîtrisant les pannes qu'il ... gestion des risques deviennent une ...... Etre en mesure de détecter les .... variés qui s'y déroulent, avoir le contrôle du.

Le rôle de l’audit interne dans le pilotage et la performance du système de contrôle interne : cas d’un échantillon d’entreprises algériennes

OpenAIRE

Chekroun, Meriem

2013-01-01

Les scandales financiers qui ont ébranlé récemment les entreprises publiques algériennes, telle que l’entreprise Sonatrach, ont mis sur le devant de la scène la nécessité de renforcer le système de contrôle interne (SCI) qui est considéré de plus en plus comme une solution à un large éventail de problèmes latents ( les problèmes d’ordre éthique,…), y compris la fonction d’audit interne ayant un rôle prépondérant dans le pilotage et la performance du SCI. Pour ce faire, l’audit ...

Le rôle des institutions dans le processus de l’innovation ; l’apport de Thorstein Veblen

Directory of Open Access Journals (Sweden)

Diane-Gabrielle Tremblay

2007-10-01

Full Text Available Nous nous intéressons ici au rôle des institutions dans le processus de l’innovation, puisque Veblen le met en valeur. Cet apport de Veblen nous paraît déterminant pour mieux comprendre l’innovation, surtout que l’on parle de plus en plus d’une diversité de formes d’innovation (technologique, mais aussi organisationnelle, sociale et de produit, et que celles-ci sont mieux comprises lorsque l’on tient compte du rôle des institutions dans la diffusion ou le blocage de l’innovation. Veblen met aussi en évidence le caractère parfois retardataire des institutions, ainsi que la réciprocité des effets entre technologie et institutions, autant d’éléments fort pertinents pour l’analyse, encore aujourd’hui.This paper addresses the role of institutions in the process of innovation, since Veblen highlights this role. This contribution of Veblen appears determinant to better understand the process of innovation, especially in a context where we are more and more interested in various forms of innovation (technological, but also organisational, social and product innovations; these various forms of innovation are better understood and analysed when the role of institutions in their diffusion or lack of diffusion is taken into account. Veblen also highlights the fact that institutions sometimes block or slow down the process of diffusion of innovations, as well as the reciprocity of effects between technology and institutions, contributions which are all the more important for the analysis of innovation today.

Bâle 3 : Quels impacts sur le financement des pays émergents ?

OpenAIRE

Figuet, Jean-Marc; Humblot, Thomas; Lahet, Delphine

2013-01-01

La persistance de crises bancaires démontre l'incapacité des établissements de crédit à s'autoréguler. De ce fait, le Comité de Bâle étend largement le périmètre de la nouvelle règlementation prudentielle. Sur la base de la littérature sur les déterminants des flux de capitaux transfrontières et d'un GMM système, cet article analyse l'impact potentiel de l'accord Bâle 3 sur les flux de capitaux bancaires provenant des banques de 16 pays industrialisés à destination d'un panel de 30 pays émerg...

Le glaive et la chair : le pouvoir et son incarnation au temps des derniers Valois

OpenAIRE

Roux, Nicolas Le

2014-01-01

Au xvie siècle, pouvait-on concevoir la monarchie autrement qu’incarnée ? Servir le roi, c’était servir un prince auquel on était lié personnellement, et non une institution abstraite. Le monarque devait apparaître comme un compagnon pour la noblesse militaire. Henri II représentait le modèle du roi chevalier. Contrairement à son père, Charles IX ne faisait pas la guerre, mais il épuisait son corps dans d’interminables chasses. Henri III a tenu dans sa jeunesse le rôle de chef de guerre. Deve...

Le don gratuit. Le cas d'un établissement public

OpenAIRE

Barel , Yvan; Frémeaux , Sandrine

2008-01-01

Disponible en ligne : http://www.annales.org/gc/2008/gc94/barel.pdf; La logique de la réciprocité est le cadre d'analyse dominant de la relation de travail. La logique du don/contredon s'inscrit dans ce même cadre de référence, en postulant qu'aucune relation d'échange ne peut survivre à une situation d'asymétrie trop forte (MAUSS, 1924). Mais elle ajoute une idée nouvelle en mettant en exergue le " tabou du calcul " (BOURDIEU, 1980) : le désir de contredon n'est pas toujours manifesté, ni mê...

Le salaire minimum n'est pas toujours le meilleur moyen d'accroître ...

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

4 mai 2016 ... De fait, cette intervention vigoureuse sur le marché du travail est une ... la mobilité des travailleurs entre le secteur structuré et le secteur non structuré, ... On peut certes se constituer rapidement du capital politique en faisant ...

Bibliographie sélective sur le corps

Directory of Open Access Journals (Sweden)

Anne-Claire Rebreyend

2007-11-01

Full Text Available Ouvrages générauxBruit Zaidman Louise, Houbre Gabrielle, Klapisch-Zuber Christiane, Schmitt Pantel Pauline (dir., Le corps des jeunes filles de l'Antiquité à nos jours, Paris, Perrin, 2001.Vigarello Georges, Le propre et le sale. L'hygiène du corps depuis le Moyen Âge, Paris, Seuil, 1985.—, Le sain et le malsain : santé et mieux-être depuis le Moyen Âge, Paris, Seuil, 1993.—, Histoire de la beauté. Le corps et l'art d'embellir de la Renaissance à nos jours, Paris, Seuil, 2004.Le corps au Moy...

Rapport financier trimestriel pour le trimestre qui a pris fin le 30 juin

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

Office 2004 Test Drive User

30 juin 2016 ... Le CRDI finance des travaux de recherche appliquée ... développement international (le Centre) et lʼévolution de la ..... voie de développement et sur la mise en oeuvre des connaissances scientifiques, techniques et autres en vue .... Les accords expirent à des dates différentes, et le dernier prend fin en.

Tumelo le Moruo

Directory of Open Access Journals (Sweden)

Vuyani S. Vellem

2015-03-01

Full Text Available Paleng ya rona batho ba batsho, tumelo ya boKreste e fihlile lefatsheng la rona la Afrika Borwa mmoho le dikgoka tsa ditjhaba tsa boPhirima. BoKreste bo fihlile ka nako ya dintwa tseo mohopolo wa tsona e neng e le ho hapa lefatshe la, batho ba batsho. Ka mantswe amang, rona batho ba batsho, re ile ra qetella re le setjhaba se ileng sa hlolwa, mme lefatshe la rona la nkuwa ka dikgoka. Ka hare ho dikgoka tsena, ho ne ho dutse tumelo ya boKreste. Makgowa a ile are: �A re kwaleng mahlo re rapeleng, rona ra kwala mahlo, mme ha re qeta hore Amen, re bula mahlo, ra fumana lefatshe le nkuwe matsohong a rona ho setse Bibele.� Re ile ra sala le Bibele eo ka yona re lekileng dilemong tse fitileng ho lwana ntwa ya topollo, kapa tokoloho hofihlela selemong sa 1994. Le ha re ile ra fumana tokoloho ka selemo seo, hare so ka re lokoloha ho tsa moruo. E kaba sena se bolela eng mabapi le tumelo ya rona ya boKreste? Segolweng sena re leka ho araba potso ena. Tumelo ke eng ho batho ba sa lokolohang moruong wa naha ya bona? Re lekola pale ya boKreste, tumelo ya batho le maemo a kereke ntlheng ya ho tadimana le tokoloho ka tumelo.Faith and economics. In our history from a black perspective, Christianity arrived through violent conquest from the west. Evidentially, this faith coincided with wars of dispossession and the ultimate defeat of black Africans. It is difficult to separate the violent defeat of black Africans from the arrival of Christian faith. This well-known statement within the circles of black Theology of liberation: When the white man arrived in our land he said, �let us pray and after prayer, when we opened our eyes, our land was taken and only the Bible was left in our hands,� captures the black sentiment of this history. Ironically, it was this Bible that black Africans used to wage their struggle for liberation up to the demise of apartheid in 1994.Nonetheless, political liberation is not enough as the struggle for economic liberation

Quantitative analysis of nickel in zirconium and zircaloy; Dosage du nickel dans le zirconium et dans le zircaloy

Energy Technology Data Exchange (ETDEWEB)

Rastoix, M [Commissariat a l' Energie Atomique, Saclay (France). Centre d' Etudes Nucleaires

1957-07-01

A rapid spectrophotometric has been developed for determination of 10 to 1000 ppm of Ni in zirconium and zircaloy using dimethylglyoxime. Iron, copper, tin and chromium, do not interfere at the concentration usually present in zirconium and its alloys. (author) [French] On determine colorimetriquenent 10 a 1000 ppm de Ni dans le zirconium et le zircaloy par photo colorimetrie a 440 m{mu} de la dimethylglyoxime nickelique. Le dosage est rapide. Le fer, le cuivre, l'etain, le chrome ne genent pas aux concentrations habituellement rencontrees dans le zirconium et ses alliages. (auteur)

Exogenous HGF Bypasses the Effects of ErbB Inhibition on Tumor Cell Viability in Medulloblastoma Cell Lines.

Directory of Open Access Journals (Sweden)

Walderik W Zomerman

Full Text Available Recent clinical trials investigating receptor tyrosine kinase (RTK inhibitors showed a limited clinical response in medulloblastoma. The present study investigated the role of micro-environmental growth factors expressed in the brain, such as HGF and EGF, in relation to the effects of hepatocyte growth factor receptor (MET and epidermal growth factor receptor family (ErbB1-4 inhibition in medulloblastoma cell lines. Medulloblastoma cell lines were treated with tyrosine kinase inhibitors crizotinib or canertinib, targeting MET and ErbB1-4, respectively. Upon treatment, cells were stimulated with VEGF-A, PDGF-AB, HGF, FGF-2 or EGF. Subsequently, we measured cell viability and expression levels of growth factors and downstream signaling proteins. Addition of HGF or EGF phosphorylated MET or EGFR, respectively, and demonstrated phosphorylation of Akt and ERK1/2 as well as increased tumor cell viability. Crizotinib and canertinib both inhibited cell viability and phosphorylation of Akt and ERK1/2. Specifically targeting MET using shRNA's resulted in decreased cell viability. Interestingly, addition of HGF to canertinib significantly enhanced cell viability as well as phosphorylation of Akt and ERK1/2. The HGF-induced bypass of canertinib was reversed by addition of crizotinib. HGF protein was hardly released by medulloblastoma cells itself. Addition of canertinib did not affect RTK cell surface or growth factor expression levels. This manuscript points to the bypassing capacity of exogenous HGF in medulloblastoma cell lines. It might be of great interest to anticipate on these results in developing novel clinical trials with a combination of MET and EGFR inhibitors in medulloblastoma.

Le Bon, Gustave

DEFF Research Database (Denmark)

Borch, Christian

2017-01-01

Gustave Le Bon (1841–1931) was a French physician and crowd psychologist who published extensively on themes such as crowds, war, race, revolution, socialism, and war. His work on crowd psychology in particular was highly influential, including beyond scholarly circles. Le Bon argued that crowds...

Le Conseil des gouverneurs | CRDI - Centre de recherches pour le ...

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

2 nov. 2010 ... La gouvernance du CRDI. Reddition de comptes, transparence et efficacité. Au cours de l'exercice 2009–2010, le Conseil des gouverneurs du CRDI a adopté un nouveau cadre stratégique quinquennal, Le développement par l'innovation. Pendant de nombreux mois, les gouverneurs et les membres de la ...

Le Service Accueil et Contrôle d'Accès

CERN Document Server

Ducastel, C

1999-01-01

L'utilisateur qui vient au CERN pour la première fois, est accueilli généralement par les membres du service 'Accueil et Contrôle d'Accès'. Cet utilisateur sera tout d'abord orienté vers un des postes d'hôtesses d'accueil en charge de l'enregistrement et de la délivrance de cartes CERN. Les informations seront saisies et immédiatement disponibles et transmises, via le système AMS, aux équipements de contrôle d'accès et à la Centrale de Surveillance des accès, chargée de la supervision de tout le dispositif de contrôle d'accès au domaine. Ces contrôles aux entrées et accueil des visiteurs individuels sont complétés par des missions de surveillance à l'intérieur du Domaine pour les agents, et par des travaux de gestions de dossiers administratifs (service enregistrement) pour les hôtesses. Un contrat commun assure une uniformité de formation des agents et hôtesses. Ce contrat est assorti d'une clause de Bonus Malus afin de tendre vers une optimisation des performances.

Use of the Charge/Discharge (C/D) ratio to aument voltage limit (V sub T) charge control in the ERBS spacecraft

Science.gov (United States)

Halpert, G.

1982-01-01

A 50-ampere hour nickel cadmium cell test pack was operated in a power profile simulating the orbit of the Earth Radiation Budget Satellite (ERBS). The objective was to determine the ability of the temperature compensated voltage limit (V sub T) charge control system to maintain energy balance in the half sine wave-type current profile expected of this mission. The four-cell pack (50 E) was tested at the Naval Weapons Support Center (NWSC) at Crane, Indiana. The ERBS evaluation test consisted of two distinct operating sequences, each having a specific purpose. The first phase was a parametric test involving the effect of V sub T level, temperature, and Beta angle on the charge/discharge (C/D) ratio, an indicator of the amount of overcharge. The second phase of testing made use of the C/D ratio limit to augment the V sub T charge limit control. When the C/D limit was reached, the current was switched from the taper mode to a C/67 (0.75 A) trickle charge. The use of an ampere hour integrator limiting the overcharge to a C/67 rate provided a fine tuning of the charge control technique which eliminated the sensitivity problems noted in the initial operating sequence.

Le paradigme du Mur dans le monde contemporain : évolution et perspectives 1989-2009

Directory of Open Access Journals (Sweden)

Hélène Yèche

2010-06-01

Full Text Available Il y a près de vingt ans, dans la nuit du 9 au 10 novembre 1989, disparaissait le mur de Berlin, symbole de la séparation de l’Europe en deux blocs antagonistes – d’un côté le camp soviétique, de l’autre le camp occidental. Le véritable tournant de ce que l’on a ensuite appelé la « révolution pacifique » eut cependant lieu un mois auparavant, le 9 octobre 1989, avec la première manifestation de masse qui réunit environ 70 000 personnes à Leipzig, RDA (ville plus tard honorée du titre de Helde...

Le corps dans l’espace architectural. Le Corbusier, Claude Parent et Henri Gaudin

Directory of Open Access Journals (Sweden)

Julie Cattant

2016-12-01

Full Text Available Le premier geste de l’espace architectural est d’accueillir nos corps humains. En leur offrant un espacement à habiter, il leur permet de s’abriter, de se mouvoir et de se rencontrer. L’homme et l’architecture s’affectent l’un l’autre. Nombreux sont les architectes qui interrogent cette coexistence car, renouveler la pensée de l’espace nécessite de reconsidérer le corps humain. L’étude des relations entre le corps et l’espace chez trois architectes français sera l’occasion d’évoquer les écarts et les convergences entre l’homme et l’architecture. L’œuvre de Le Corbusier, protagoniste du mouvement moderne, maintient ainsi une distance entre un corps machinisé et un espace idéal. Marquée par un mode de pensée dualiste, l’architecture de Le Corbusier annonce toutefois son propre dépassement, dépassement que Claude Parent et Henri Gaudin opèreront par la suite à leur manière, le premier en introduisant l’oblique et la déstabilisation du corps, le second en transgressant la limite de l’espace et du corps pour envisager leur porosité réciproque. Finalement, c’est la manière dont l’homme appréhende l’espace avec son corps qui est questionnée par ces trois architectes, de la prégnance du visuel à son évincement.

Beware of ligand efficiency (LE): understanding LE data in modeling structure-activity and structure-economy relationships.

Science.gov (United States)

Polanski, Jaroslaw; Tkocz, Aleksandra; Kucia, Urszula

2017-09-11

On the one hand, ligand efficiency (LE) and the binding efficiency index (BEI), which are binding properties (B) averaged versus the heavy atom count (HAC: LE) or molecular weight (MW: BEI), have recently been declared a novel universal tool for drug design. On the other hand, questions have been raised about the mathematical validity of the LE approach. In fact, neither the critics nor the advocates are precise enough to provide a generally understandable and accepted chemistry of the LE metrics. In particular, this refers to the puzzle of the LE trends for small and large molecules. In this paper, we explain the chemistry and mathematics of the LE type of data. Because LE is a weight metrics related to binding per gram, its hyperbolic decrease with an increasing number of heavy atoms can be easily understood by its 1/MW dependency. Accordingly, we analyzed how this influences the LE trends for ligand-target binding, economic big data or molecular descriptor data. In particular, we compared the trends for the thermodynamic ∆G data of a series of ligands that interact with 14 different target classes, which were extracted from the BindingDB database with the market prices of a commercial compound library of ca. 2.5 mln synthetic building blocks. An interpretation of LE and BEI that clearly explains the observed trends for these parameters are presented here for the first time. Accordingly, we show that the main misunderstanding of the chemical meaning of the BEI and LE parameters is their interpretation as molecular descriptors that are connected with a single molecule, while binding is a statistical effect in which a population of ligands limits the formation of ligand-receptor complexes. Therefore, LE (BEI) should not be interpreted as a molecular (physicochemical) descriptor that is connected with a single molecule but as a property (binding per gram). Accordingly, the puzzle of the surprising behavior of LE is explained by the 1/MW dependency. This effect

Le paludisme, le tsunami silencieux d'Afrique | IDRC - International ...

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

12 janv. 2011 ... Dans un élan de compassion fort justifié, le monde s'est porté au secours des victimes du tsunami qui a touché récemment la région de l'océan Indien. Mais il ignore qu'un « tsunami silencieux », le paludisme, s'abat sans cesse sur l'Afrique et y fait chaque année plus de 1,5 million de victimes, surtout de ...

Le Peer to Peer: Vers un Nouveau Modèle de Civilisation

Directory of Open Access Journals (Sweden)

Michel Bauwens

2006-06-01

Full Text Available Le « peer to peer » est la dynamique intersubjective caractéristique des réseaux distribués. Le but de cet essai est de montrer qu’il s’agit d’une véritable nouvelle forme d’organisation sociale, apte à produire et échanger des biens, à créer de la valeur. Celle-ci est la conséquence d’un nouvel imaginaire social, et possède le potentiel de devenir le pilier d’un nouveau mode d’économie politique, voire d’un nouveau type de civilisation. Pour cela, nous allons d’abord définir le P2P, décrire en bref ces manifestations, et le différencier d’autres modalités d’échange intersubjectif tel que le marché, la hiérarchie, l’économie du don. Comme principale modalité P2P nous distinguons: Les processus de production P2P, comme troisième mode de production, qui n’est ni géré par un mode hiérarchique ou par l’état, ni répondant à des impératifs de profit ou qui sont modulés par le biais des prix. Les processus de gouvernance P2P, qui gouverne ces processus de production. Les formes de propriété P2P, qui sont destine a empecher l’appropriation prive de cette production pour le commun. Afin d’examiner les characteristiques de cette nouvelle dynamique sociale, nous utilisons la typologie intersubjective de l’anthropologue Alan Page Fisque, qui distingue: 1. l’échange égalitaire (Equality Matching, c..a.d l’economie du don. 2. La relation d’autorité (Authority Ranking tel qu’elle s’exprime dans le mode hierarchique. 3. le marché (Market Pricing. 4. la participation commune (Communal Shareholding. En conclusion, nous examinons les possibilites d’expansion de ce nouveau mode sociale et son insertion dans l’economie capitaliste, en nous nous posons la question: le P2P peut-il etre concu comme alternative sociale et economique aux modeles existants. Abstract: “Peer to peer” is hypothesized as a new social formation with intersubjective dynamics characteristic of distributed

La piraterie sur le web

CERN Multimedia

2002-01-01

Les échanges de toutes sortes sont facilités à l'extrême par le web: des forums, des vidéoconférences, le commerce à distance, ou tout simplement la célérité des courriers électroniques ou la convivialité des chats, tout cela participe de la société de communication. Une certaine partie du monde découvre le nouvel horizon des échanges quasi instantanés, mais... les transactions sur le web sont-elles vraiment s res?

Valuing Heritage in Macau: On Contexts and Processes of Urban Conservation Kulturelles Erbe in Macau: Zu Rahmenbedingungen und Prozessen städtischer Denkmalpflege

Directory of Open Access Journals (Sweden)

Thomas Chung

2009-04-01

Full Text Available This paper examines the evolving values of urban heritage in Macau in terms of the various conservation approaches and mechanisms employed, and the shifting emphases on heritage and development within the context of continuity and change in Macau. Accumulated over four centuries of cultural interchange, the richly layered Historic Centre of the former Portuguese-administered outpost attained World Heritage status in 2005. After situating the problem pertaining to the multifaceted nature of heritage valorisation, the city’s trajectory of urban conservation leading up to the 1999 retrocession will be traced, and germane issues concerning heritage management vis-à-vis effects of post-handover urban developments assessed. As the latest culmination of value imbalances and conflicts arising from urban change, the Guia Lighthouse controversy will be critically appraised to speculate on a timely re-evaluation of Macau’s heritage conservation process. Der vorliegende Beitrag untersucht die sich wandelnde Haltung in Macau zum eigenen kulturellen Erbe, und zwar mit Blick auf die verschiedenen Konservierungsansätze und die dazu angewandten Methoden sowie auf die unterschiedliche Bedeutung von Kulturellem Erbe und Entwicklung im Kontext von Kontinutät und Wandel in der Stadt.

Dans le tourbillon des particules

CERN Document Server

Zito, Marco

2015-01-01

Accélérateurs géants, détecteurs complexes, particules énigmatiques... La physique subatomique peut sembler bien intimidante pour le novice. Et pourtant, qui n a jamais entendu parler du boson de Higgs et du CERN, le laboratoire européen où il a été découvert en 2012 ? Nul besoin d être un spécialiste pour comprendre de quoi il s agit. Aujourd hui, une théorie extraordinairement élégante, le Modèle Standard, décrit tous les résultats des expériences dans le domaine. Trente-sept particules élémentaires et quatre forces fondamentales : c est tout ce dont nous avons besoin pour expliquer la matière et l Univers ! Ce livre, destiné à un large public, raconte sans équations le long parcours qui a abouti au Modèle Standard. Ce parcours, parfois sinueux, a été entamé lorsque les Grecs anciens, et peut-être d autres avant eux, ont imaginé que la matière est composée de petites « billes ». Il faudra attendre plusieurs siècles pour qu on réalise que la matière, à l échelle micros...

Le SRAS, le sida, et la santé publique | IDRC - International ...

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

22 juil. 2011 ... Certaines de ces leçons portent sur les interactions complexes entre la biologie, la culture et le pouvoir. D'autres traitent des moyens de .... HIV prevention policy in China. IDRC-funded research is using mathematical modelling to influence local and national policies in China to reduce HIV transmission.

La science, la littérature, le rituel: le vrai dire et le plus que mentir

Directory of Open Access Journals (Sweden)

Panagiotis Christias

2005-03-01

Full Text Available Le scientifique promet la vérité sans être en mesure d'accomplir sa promesse tandis que l'écrivain promet de mentir mais par son mensonge, il fait plus que mentir. Il ne dit certainement pas la vérité, car la vérité n'est pas sa préoccupation première. Voilà comment nous pouvons résumer les deux attitudes, condamnées à un antagonisme stérile par l'attitude positiviste moderne. Compte tenu donc de l'intention fondatrice de la science, de sa promesse donc originaire et fondatrice, la science doit dire la vérité et rien que la vérité. Ce qui, de l'aveu même de cette même science, est impossible. [...] La littérature se permet de reconstruire des mondes par-delà le vrai et le faux. [...] Un récit littéraire ne demande pas la consécration de la vérité, ne demande pas à être suivi parce que vrai, n'impose rien et n'attend rien. Sa vraie destinée est l'errance et sa vraie conscience est celle de sa dissémination. Celui qui renonce à la prétention de vérité renonce en même temps à la volonté de dominer. Dominer signifie créer un espace de vérité dans lequel celui qui énonce la vérité est le maître légitime de ceux qui sont dans le champ de la conception du monde dont cette vérité est la pierre angulaire.

Role of RBP2-Induced ER and IGF1R-ErbB Signaling in Tamoxifen Resistance in Breast Cancer.

Science.gov (United States)

Choi, Hee-Joo; Joo, Hyeong-Seok; Won, Hee-Young; Min, Kyueng-Whan; Kim, Hyung-Yong; Son, Taekwon; Oh, Young-Ha; Lee, Jeong-Yeon; Kong, Gu

2018-04-01

Despite the benefit of endocrine therapy, acquired resistance during or after treatment still remains a major challenge in estrogen receptor (ER)-positive breast cancer. We investigated the potential role of histone demethylase retinoblastoma-binding protein 2 (RBP2) in endocrine therapy resistance of breast cancer. Survival of breast cancer patients according to RBP2 expression was analyzed in three different breast cancer cohorts including METABRIC (n = 1980) and KM plotter (n = 1764). RBP2-mediated tamoxifen resistance was confirmed by invitro sulforhodamine B (SRB) colorimetric, colony-forming assays, and invivo xenograft models (n = 8 per group). RNA-seq analysis and receptor tyrosine kinase assay were performed to identify the tamoxifen resistance mechanism by RBP2. All statistical tests were two-sided. RBP2 was associated with poor prognosis to tamoxifen therapy in ER-positive breast cancer (P = .04 in HYU cohort, P = .02 in KM plotter, P = .007 in METABRIC, log-rank test). Furthermore, RBP2 expression was elevated in patients with tamoxifen-resistant breast cancer (P = .04, chi-square test). Knockdown of RBP2 conferred tamoxifen sensitivity, whereas overexpression of RBP2 induced tamoxifen resistance invitro and invivo (MCF7 xenograft: tamoxifen-treated control, mean [SD] tumor volume = 70.8 [27.9] mm3, vs tamoxifen-treated RBP2, mean [SD] tumor volume = 387.9 [85.1] mm3, P < .001). Mechanistically, RBP2 cooperated with ER co-activators and corepressors and regulated several tamoxifen resistance-associated genes, including NRIP1, CCND1, and IGFBP4 and IGFBP5. Furthermore, epigenetic silencing of IGFBP4/5 by RBP2-ER-NRIP1-HDAC1 complex led to insulin-like growth factor-1 receptor (IGF1R) activation. RBP2 also increased IGF1R-ErbB crosstalk and subsequent PI3K-AKT activation via demethylase activity-independent ErbB protein stabilization. Combinational treatment with tamoxifen and PI3K inhibitor could overcome RBP2-mediated tamoxifen

48. Le pavillon Liliane de Stewart

OpenAIRE

Cameron, Christina; Déom, Claudine; Valois, Nicole

2018-01-01

Le pavillon Liliane de Stewart Le pavillon Liliane de Stewart est situé à l’arrière du pavillon Marguerite-d’Youville, qui lui est mitoyen. Il en constitue en quelque sorte un agrandissement, mais il s’en différencie par son plus petit volume (trois étages). Les deux pavillons partagent quelques caractéristiques architecturales, dont le plan angulaire et le revêtement de brique chamois. Le pavillon Liliane de Stewart se distingue cependant par sa fenestration, surtout celle de la façade avant...

Le cosmos et le lotus confessions d'un astrophysicien

CERN Document Server

Trinh, Xuan Thuan

2011-01-01

Que nous dit vraiment la science sur la nature de l'univers, sur son origine et son avenir ? Par quel mystère le langage mathématique, pure création de l'esprit humain, se révèle-t-il aussi performant pour nous décrire les phénomènes physiques, de l'infiniment petit à l'infiniment grand ? S'il existe un ordre du monde, ce que nous en disent la physique quantique et la théorie de la relativité est-il compatible avec ce qu'enseigne le bouddhisme ? Et que peut-on en conclure concernant notre propre vie ? A ces questions passionnantes et à beaucoup d'autres, le célèbre astrophysicien Trinh Xuan Thuan répond ici d'une façon personnelle, en s'appuyant sur son expérience. Son itinéraire l'a placé d'emblée à la confluence de trois cultures : issu d'une famille de lettrés vietnamiens imprégnée de traditions bouddhiste et confucéenne, il a reçu une éducation à la française puis une formation scientifique à l'américaine. Une telle richesse de points de vue lui permet d'apporter, non pas de...

Accessibilité aux emplois en France : le rôle de la distance à la ville

Directory of Open Access Journals (Sweden)

Mohamed Hilal

2004-12-01

Full Text Available L'objet de cet article est de modéliser les niveaux d’accessibilité potentielle aux emplois des communes françaises selon le rôle de la distance à la ville. Pour ce faire, nous présentons, tout d’abord, un modèle d’accessibilité et la méthode mise en œuvre pour calculer de façon systématique, à partir des données du réseau routier, une matrice des plus courts chemins, mesurés en temps, entre les communes françaises. Ensuite, dans la deuxième partie, ces distances sont intégrées dans le modèle d’accessibilité retenu afin de mesurer la disponibilité potentielle aux emplois selon la distance au pôle urbain le plus proche et selon les principales catégories d’espace du zonage en aires urbaines et de son complément rural. Enfin, la mesure d’accessibilité potentielle est comparée à plusieurs mesures d’accessibilité empirique.

Le fictif et le réel dans L’Empereur et l’assassin de Chen Kaige

OpenAIRE

Giafferri, Xiaomin

2008-01-01

Comme tout texte historique littéraire refait l’Histoire en la manipulant, le récit filmique est doublement mensongère du fait de sa double représentation : le décor et les acteurs représentent une situation qui est la fiction, et le film lui-même représente sous forme d’images juxtaposées cette première représentation. Sans vouloir faire la part du réel et de l’imaginaire, le présent travail tente de montrer comment, dans le film L’empereur et l’assassin de Chen Kaige, l’illusion de l’authen...

pour le trimestre qui a pris fin le 30 juin 2013

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

Office 2004 Test Drive User

30 juin 2013 ... Conseil des gouverneurs du CRDI. Le mandat des gouverneurs suivants a pris fin le 27 mai 2013 : Margaret Biggs, d'Ottawa, en Ontario;. Faith Mitchell, de Washington, aux États-Unis; Elizabeth Parr-Johnston, de Chester Basin, en Nouvelle-Écosse; Gordon Shirley, de Kingston, en Jamaïque; l'honorable ...

Le droit, l'économie et le fondamental

OpenAIRE

Gérard Farjat

2005-01-01

MAITRE Grégory, préf. MUIR WATT Horatia, La Responsabilité civile à l’épreuve de l’analyse économique du droit, Paris, L.G.D.J., coll. Droit &Économie, 2005,315 p. LE TOURNEAU Philippe, L’Éthique des affaires et du management au XXIe siècle, Paris, Dalloz, Paris, Dunod, 2000,269 p. DELMAS-MARTY Mireille, Le Relatif et l’universel : les forces imaginantes du droit, Paris, Seuil, coll. La Couleur des idées, 2004,440 p. FRISON-ROCHE Marie-Anne, BONFILS Sébastien, Les Grandes Questions du droit é...

Le FIVB annonce le financement de huit autres projets | CRDI ...

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

5 avr. 2018 ... Découvrez les derniers récents projets soutenus par le Fonds d'innovation en matière de vaccins pour le bétail : Maladie de Newcastle · Pleuropneumonie contagieuse caprine – cowdriose · Plateforme de modification génétique CRISPR/cas9 · Entérotoxémie, la bactérie Pasteurella et la fièvre de la vallée ...

pour le trimestre qui a pris fin le 30 septembre 2016

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

Office 2004 Test Drive User

30 sept. 2016 ... Le CRDI finance des travaux de recherche appliquée ... internationales dʼinformation financière (normes IFRS). ..... voie de développement et sur la mise en oeuvre des connaissances scientifiques, techniques et autres en vue du .... Les accords expirent à des dates différentes, et le dernier prend fin en.

Le barrage des trois Gorges (Chine

Directory of Open Access Journals (Sweden)

Luc Merchez

1999-09-01

Full Text Available Le barrage des Trois Gorges, en construction sur le Yangzijiang, sera le plus grand barrage au monde. Le gigantisme du projet et sa médiatisation croissante en Occident permettent d'en saisir les enjeux environnementaux et humains. On analyse les grandes caractéristiques du projet et ses conséquences premières avant d'aborder le travail de recherche de l'équipe SIG de l'IGA de Grenoble qui vise à préparer la relocalisation de plus d'un million d'habitants, et à modéliser les impacts démographiques et sociaux.

Discovery of new erbB4 inhibitors: Repositioning an orphan chemical library by inverse virtual screening.

Science.gov (United States)

Giordano, Assunta; Forte, Giovanni; Massimo, Luigia; Riccio, Raffaele; Bifulco, Giuseppe; Di Micco, Simone

2018-04-12

Inverse Virtual Screening (IVS) is a docking based approach aimed to the evaluation of the virtual ability of a single compound to interact with a library of proteins. For the first time, we applied this methodology to a library of synthetic compounds, which proved to be inactive towards the target they were initially designed for. Trifluoromethyl-benzenesulfonamides 3-21 were repositioned by means of IVS identifying new lead compounds (14-16, 19 and 20) for the inhibition of erbB4 in the low micromolar range. Among these, compound 20 exhibited an interesting value of IC 50 on MCF7 cell lines, thus validating IVS in lead repurposing. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Le rôle de l'IL6 dans le cancer du foie lié à l'hépatopathie métabolique

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

Le cancer du foie est souvent mortel. Il n'existe que très peu d'options de traitement, et il s'agit de l'un des cancers dont l'incidence augmente dans le monde entier. L'obésité ou les maladies métaboliques (comme le diabète et la stéatose hépatique) constituent des facteurs de risque du cancer du foie qui sont mal compris.

Rapport financier trimestriel pour le trimestre qui a pris fin le 30 ...

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

Sophie Comeau

30 sept. 2017 ... Régi par la Loi sur le Centre de recherches pour le développement international ... forme des leaders dans les secteurs de l'administration publique, de la .... Plus des trois quart du manque à gagner prévu de 11,6 millions.

Nicolas Michel, Une économie de subsistances. Le Maroc précolonial, IFAO, Le Caire, 1997.

Directory of Open Access Journals (Sweden)

Sylvie Denoix

2004-11-01

Full Text Available Le titre de cet ouvrage peut apparaître paradoxal si l'on considère, comme le rappelle Nicolas Michel, que le Maroc, dès avant le XIXe siècle, était inséré dans une économie marchande internationale "faisant circuler dans tout le pays produits et espèces monétaires". En fait, les produits de première nécessité échappent au grand négoce et font plutôt l'objet d'un troc, d'un échange contre services, hors système monétaire. Néanmoins, dans un souci de rigueur méthodologique, l'auteur nous garde...

Le CRDI en Égypte

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

afin d'y favoriser la croissance et le développement. Il en résulte des solutions locales, novatrices et durables, qui offrent des choix aux personnes qui en ont le plus besoin et font changer les choses. Centre de recherches pour le développement international. CP 8500, Ottawa (Ontario) Canada K1G 3H9. 1012 alexandrie.

Le CRDI en Indonésie

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

l'État dans l'île de Java. Soutenu par le CRDI, l'institut Lembaga Alam Tropika Indonesia. (ou LATIN) a conçu un modèle de cogestion des forêts qui met à contribution les collec- tivités et le gouvernement dans trois dis- tricts. Ainsi, les agriculteurs disposent d'un meilleur accès aux ressources de la forêt. Évaluation des ...

Le shopping mall : un modèle pour la construction de la ville ?

OpenAIRE

Daniau, Anaïs

2017-01-01

Après avoir montré à quel point le renouvellement du concept de shopping mall s’était inspiré de la ville, le présent article souhaite symétriser l’analyse de cette relation en décrivant la manière dont la gestion des centres urbains emprunte au fonctionnement des centres commerciaux pour se réinventer. Cette référence croissante au centre commercial comme modèle d’efficacité par les gestionnaires de centre-ville révèle selon nous l’existence de processus plus larges touchant nos centres-vill...

Rapport financier trimestriel pour le trimestre qui a pris fin le 31 ...

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

Sophie Comeau

31 déc. 2017 ... Régi par la Loi sur le Centre de recherches pour le développement international ... optimiser les retombées; forme des leaders dans les secteurs de ... Centre dans ce domaine, et a animé une table ronde avec trois des quatre ...

Le partenariat mondial sur les données ouvertes pour le ...

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

Les données ouvertes favorisent le changement. Au Brésil, au Népal et au Nigeria, certaines personnes utilisent les données publiquement accessibles sur le budget gouvernemental pour repérer et combattre la corruption. Des analystes de données et des développeurs en TI d'autres pays en développement améliorent ...

pour le trimestre qui a pris fin le 30 septembre 2012

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

acray

30 sept. 2012 ... recommande de lire ce rapport en parallèle avec les états financiers non audités (à la page 9). L'information et les .... développement ont augmenté de 56,9 % par rapport au même trimestre de l'exercice 2011-2012 ..... IFRS) telles que publiées par le Conseil des normes comptables internationales (CNCI).

Model-based global sensitivity analysis as applied to identification of anti-cancer drug targets and biomarkers of drug resistance in the ErbB2/3 network

Science.gov (United States)

Lebedeva, Galina; Sorokin, Anatoly; Faratian, Dana; Mullen, Peter; Goltsov, Alexey; Langdon, Simon P.; Harrison, David J.; Goryanin, Igor

2012-01-01

High levels of variability in cancer-related cellular signalling networks and a lack of parameter identifiability in large-scale network models hamper translation of the results of modelling studies into the process of anti-cancer drug development. Recently global sensitivity analysis (GSA) has been recognised as a useful technique, capable of addressing the uncertainty of the model parameters and generating valid predictions on parametric sensitivities. Here we propose a novel implementation of model-based GSA specially designed to explore how multi-parametric network perturbations affect signal propagation through cancer-related networks. We use area-under-the-curve for time course of changes in phosphorylation of proteins as a characteristic for sensitivity analysis and rank network parameters with regard to their impact on the level of key cancer-related outputs, separating strong inhibitory from stimulatory effects. This allows interpretation of the results in terms which can incorporate the effects of potential anti-cancer drugs on targets and the associated biological markers of cancer. To illustrate the method we applied it to an ErbB signalling network model and explored the sensitivity profile of its key model readout, phosphorylated Akt, in the absence and presence of the ErbB2 inhibitor pertuzumab. The method successfully identified the parameters associated with elevation or suppression of Akt phosphorylation in the ErbB2/3 network. From analysis and comparison of the sensitivity profiles of pAkt in the absence and presence of targeted drugs we derived predictions of drug targets, cancer-related biomarkers and generated hypotheses for combinatorial therapy. Several key predictions have been confirmed in experiments using human ovarian carcinoma cell lines. We also compared GSA-derived predictions with the results of local sensitivity analysis and discuss the applicability of both methods. We propose that the developed GSA procedure can serve as a

Les pôles de compétitivité : le recours au modèle des clusters ?

Directory of Open Access Journals (Sweden)

Jean Bouinot

2007-03-01

Full Text Available Introduction : définition d’un cluster En novembre 2004, le gouvernement a lancé un appel d’offre pour structurer des pôles de compétitivité que les praticiens français n’hésitent pas à qualifier de cluster, littéralement un rassemblement du type « bouquet de fleurs ». Pour une définition théorique on peut s’appuyer sur une comparaison avec le modèle du district industriel italien (MDII. Le district est spécialisé dans un produit donné (chaussures de sport à Montebelluna, le leader mondial e...

Luther contre le protocole de Kyoto ou le retour des « indulgences ».

Directory of Open Access Journals (Sweden)

Bernard Jouve

2005-05-01

Full Text Available Le 16 février 2005 a marqué la mise en œuvre du Protocole de Kyoto. En fait, depuis l’annonce par la Russie, le 25 octobre 2004, de sa décision de ratifier ce protocole, l’affaire était entendue. Menacé depuis le refus des États-Unis, l’un des plus grands pollueurs de la planète, de ne pas le ratifier pour des raisons purement économiques alors que ce pays produit à lui seul 40 % des gaz à effet de serre ( ges , l’accord survenu à Kyoto en 1997 est enfin entériné et ...

Le paludisme, le tsunami silencieux d'Afrique | CRDI - Centre de ...

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

12 janv. 2011 ... Dans un élan de compassion fort justifié, le monde s'est porté au secours des victimes du tsunami qui a touché récemment la région de l'océan Indien. Mais il ignore qu'un « tsunami silencieux », le paludisme, s'abat sans cesse sur l'Afrique et y fait chaque année plus de 1,5 million de victimes, surtout de ...

Sauver le café | CRDI - Centre de recherches pour le ...

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

D'un tiroir de la collection entomologique de Cenicafé, où sont conservés 38 000 spécimens, Álvaro Gaitán extrait le coupable, un minuscule insecte brunâtre qui a fait perdre à lui seul un demi-milliard de dollars par an à l'industrie du café dans les dernières années. Le scolyte du caféier (la broca, en espagnol) se nourrit ...

Characterization of purple and green photosynthetic bacteria isolated from the lagoon of Agatti Atoll (Lakshadweep Sea)

Digital Repository Service at National Institute of Oceanography (India)

LokaBharathi, P.A.; Chandramohan, D.

, H. medicinalis. Lastly, the denticles are distinctly sharper and more acute-tipped than those of P. granulosa. The presence of such a denticular curvature and acute tip obviously adds to the sawing efficiency of the jaws of the land-leeches during... around the denticles. In short, a denticle not only pours saliva but is bathed by it also during microincision. A similar intra-denticular salivary discharge has been reported by Damas2 in H. medicinalis. The author is grateful to Dr V. K. Bajpai for help...

Dohmen, Dieter, Erbes, Annegret, Fuchs, Kathrin & Günzel, Juliane (2008). Was wissen wir über Nachhilfe? Sachstand und Auswertung der Forschungsliteratur zu Angebot, Nachfrage und Wirkungen. Bielefeld: Bertelsmann, 150 S. [Rezension

OpenAIRE

Mayr, Thomas

2014-01-01

Rezension von Dohmen, Dieter, Erbes, Annegret, Fuchs, Kathrin & Günzel, Juliane (2008). Was wissen wir über Nachhilfe? Sachstand und Auswertung der Forschungsliteratur zu Angebot, Nachfrage und Wirkungen. Bielefeld: Bertelsmann, 150 S. 29,90 EUR, ISBN 978-3763936656

Le continu contre l'espace

Science.gov (United States)

Salanskis, Jean-Michel

Disons pour conclure que, en tout état de cause, la façon de concevoir philosophiquement le conflit du continu et de l'espace que nous avons trouvée chez Hegel n'est pas homogène avec le style et les modalités de la pensée mathématique: 1) d'une part, le lien classique, le lien de référence entre continu et espace en mathématiques n'est pas que l'espace serait premier et privé de pensée, et le continu second, venant dissoudre l'espace en apportant la qualité, l'infini et la pensée, mais tout au contraire, il consiste en ce que l'espace est fondé sur l'abîme infinitaire du continu ; 2) d'autre part, l'éventuel divorce entre l'espace et le continu dans l'aire mathématique n'est pas celui d'une réflexivité purement conceptuelle du continu avec un positivisme géométrique, n'équivaut pas à une rupture disciplinaire ; il est plutôt le symptôme de la dérive d'une herméneutique à l'égard d'une autre, au sein d'un continent juridique commun définissant la discipline (la mathématique ensembliste), cette dérive pouvant, à la limite, induire une refonte de ce sol juridique, sans que jamais il soit question pour autant de nier l'unité des mathématiques, à comprendre ici comme l'unité ultime de responsabilité de la communauté mathématique à l'égard des trois questions Qu'est-ce que l'espace?”, “Qu'est-ce que le continu?” et “Qu'est-ce que l'infini?”.

Le surpoids, l'obésité et le contrôle glycémique chez les diabétiques ...

African Journals Online (AJOL)

utilisation et du stockage des sucres apportés par l'alimentation, sa prise en charge est ... l'organisation mondiale de santé (OMS), Le contrôle glycémique a été effectué par l'analyse sanguine de l'Hémoglobine glycosylée et de la Glycémie à jeun.

Rapport financier trimestriel pour le trimestre qui a pris fin le 31

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

Sophie Comeau

31 déc. 2011 ... politiques, de chercheurs et de collectivités de par le monde. ..... qui a été choisi à l'issue d'un processus de recrutement mené ... Les bureaux régionaux constituent une ressource stratégique et un élément clé du modèle de.

Rapport financier trimestriel pour le trimestre qui a pris fin le 31

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

Office 2004 Test Drive User

31 déc. 2016 ... Le CRDI finance des travaux de recherche appliquée ... développement international (le Centre) et lʼévolution de la ...... voie de développement et sur la mise en oeuvre des connaissances scientifiques, techniques et autres en vue du .... vertu d'accords de contribution conclus avec des bailleurs de fonds.

Bibliographie de l’île de Clipperton – Île de La Passion (1711-2005)

OpenAIRE

Jost, Christian

2008-01-01

L’île de Clipperton, baptisée « Île de La Passion » par ses découvreurs français en 1711, porte pourtant le nom d’un pirate anglais. Malgré les très courtes périodes d’occupation qu’elle connut au début du XXe siècle et dans les années 1960, son histoire est jalonnée de nombreux écrits. Son intérêt scientifique sur le plan des études environnmentales et les enjeux économique et géopolitique récemment renouvelés conduisent l’auteur à publier ici cette bibliographie de plus de trois cent cinqua...

Lutter contre le paludisme sans DDT

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

Nancy Minogue

La participation de la collectivité aux stratégies de contrôle, une surveillance ... Le contrôle de la maladie passe par une meilleure gestion de l'environnement. En vertu de ... de la santé humaine, ou écosanté, est un processus dynamique qui.

PERFORMANCE ET RESTRUCTURATION: LE CAS SAÏDAL ...

African Journals Online (AJOL)

performance de SAÏDAL suite à sa restructuration débutée en 1997. Le concept de ... millions d'actions. Du point de vue du management, SAÏDAL adopte le tableau de .... Méthodes et Pratiques de la Performance : Le Guide du Pilotage. ... performance des entreprises, Kaplan et Norton proposèrent le tableau de bord ...

Le Valais et ses Reines

Directory of Open Access Journals (Sweden)

Alberto Campi

2012-06-01

Full Text Available Combat de ReinesAu premier plan (la corde dans la main, un propriétaire de vaches. Dans l'arène se trouve le rabatteur. Les Reines sur la photo sont des reines de première catégorie (ainsi que le montre le « I » sur leur cuisse .Dimanche 6 mai 2012, « Schakira », la vache numéro 42, a gagné, non sans polémique, le titre de Reine. Elle peut donc être considérée comme la Reine des Reines, titre qu’elle a gagné en se battant contre ses rivales dans différents combats, qui ont commencé pour Sch...

Quand le lait devient enjeu social : le cas de la société peule dans le Séno (Burkina Faso

Directory of Open Access Journals (Sweden)

Madina Querre

2003-09-01

Full Text Available L’intérêt pour le « lait » en tant que sujet de recherche est issu, ici, de questionnements autour de l’allaitement en tant que facteur de transmission du VIH. En effet, la transmission du VIH par l’allaitement représente un important problème de santé publique dans les pays du Sud. La mise en place des programmes de prévention reste un problème complexe qui touche divers domaines dont une partie concerne directement notre discipline, étant d’ordre social et culturel. Les perceptions qui valorisent l’allaitement maternel sont très ancrées dans la plupart des cultures « tradi­tionnelles », mettant en valeur celles du lait. Le lait prend en effet dans la société peule une valeur qui va au-delà de la simple question de l’allaitement, étant présent au cœur même de la structure socio-économique. C’est cet aspect qui constituera le propos de cet article.Le terme Kossam, qui désigne le lait, signifie « ce qui est meilleur ». A la base de l’organisation socio-économique peule, son exploitation révèle une originalité particulière concernant les femmes : c’est le lait qui donne aux femmes la possibilité d’une émancipation sociale et économique. En effet, tel que cela sera développé dans cet article, le lait de vache est la propriété de la femme dès l’instant où elle est mariée ; elle peut alors en disposer selon ses intérêts pour la consommation et/ou la commercialisation. Elle peut donc avoir une certaine marge de liberté dans ses actions sans être sous la tutelle complète de son époux. Le fait même qu’elle en soit propriétaire fait référence à un fonctionnement et à une représentation sociale spécifiques.Le lait et sa productrice, la vache, sont au cœur du fonctionnement socio-économique peul. Le lait est considéré comme étant à la base de l’alimentation ; même si dans les faits l’alimentation est aussi organisée autour du mil. Aussi, envisager le

Le vernis des apparences

Directory of Open Access Journals (Sweden)

Grazia Nicosia

2010-04-01

Full Text Available Le but de cet article est de comprendre l’incidence sémiotique du nettoyage d’un tableau ainsi que la résultante cognitive induite sur l’observateur. Cette étude confronte l’analyse des phénomènes visuels engendrés par le jaunissement du vernis et son retrait, à des entretiens réalisés à dessein. Le retrait d’un vernis jauni change considérablement l’image. L’heure, le climat, la saison et l’activité même des personnages s’en trouvent ainsi modifié. La patine peut être perçue, soit comme un obstacle à l’exploration, soit pour ceux qui l’apprécient, comme le medium d’une relation plus intime entre l’œuvre et l’observateur.The purpose of this article is to understand the semiotic impact of the cleaning of a painting and the cognitive effects induced on the observer. This study analyses conjointly the visual phenomenon generated by yellowing varnish and its removal and controlled interviews of observers.The removal of yellowing varnish modifies considerably the perception of the picture. Daytime, climate, season and characters activities are modified. The patina may be perceived either as an obstacle to the painting exploration, or, for those who appreciate it, as a medium for a closer relationship between the painting and the observer.

Le corps dans l'Antiquité

Directory of Open Access Journals (Sweden)

Sophie Lalanne

2008-06-01

Full Text Available Ouvrages générauxLaqueur Thomas, La fabrique du sexe. Essai sur le corps et le genre en Occident, trad. fr., Paris, Gallimard, 1992.Feher Michel, Naddaff Ramona, Tazi Nadia, Fragments for a History of the Human Body, 3 volumes, New York, Zone Books, 1989.Le Corps dans l’AntiquitéBodiou Lydie, Frère Dominique, Mehl Véronique dir., L’expression des corps. Gestes, attitudes, regards dans l’iconographie antique, Rennes, Presses Universitaires de Rennes, 2006.Bonnard Jean-Baptiste, Le complexe de ...

La filière d’oignon d’été dans le Saïs au Maroc : la place et le rôle des intermédiaires de la commercialisation

Directory of Open Access Journals (Sweden)

Caroline Lejars

2014-11-01

Full Text Available Les agriculteurs dépendent souvent, pour la commercialisation de leur produit, d'un réseau complexe d'intermédiaires privés. Dans les pays en développement, ces intermédiaires de la vente sont souvent accusés de réaliser des profits excessifs et d’être responsables des énormes écarts entre le prix de vente au champ et le prix payé par le consommateur. En s’appuyant sur l’étude de la filière oignon d’été dans le Saïs au Maroc, cet article analyse le rôle de ces réseaux d'intermédiaires, et la répartition des coûts et de la marge bénéficiaire le long de la chaine de production et de commercialisation. On montre ainsi que cette filière crée un grand nombre d'emplois en aval de la production, que ce soit pour la collecte, le stockage, le transport ou la vente. La part de la marge bénéficiaire revenant à l’ensemble des intermédiaires est supérieure à celle revenant aux producteurs, ce qui entraine effectivement une importante différence de prix entre le prix de vente et le prix du marché. Même si les profits et les rôles des intermédiaires sont très variables, certains des acteurs intermédiaires, notamment les détaillants et les revendeurs en gros, récupèrent des marges bien supérieures à celles des agriculteurs. L’organisation des producteurs autour de zones de stockage et d’activités de commercialisation permettrait de limiter le nombre d’intermédiaires, d’accroitre le profit des agriculteurs et de modifier les rapports de négociations souvent asymétriques entre agriculteurs et commerçants.

Le rôle des chefs traditionnels en Afrique | CRDI - Centre de ...

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

14 juil. 2011 ... Se fondant sur ces expériences, Ray, présentement professeur de sciences politiques à l'Université de Calgary, a mené un nouveau projet sur le rôle des chefs traditionnels dans la gouvernance locale en Afrique. Bien qu'il soient souvent ignorés par les organismes de développement international, les ...

Le nouveau modèle québécois axé sur la gouvernance

Directory of Open Access Journals (Sweden)

Jeffrey Roy

2002-10-01

Full Text Available L'article soutient qu'il a bien eu un modèle québécois de développement, mais il est devenu inefficace et remis en question. Ce modèle se distinguait par son interventionniste étatique dynamique et par la constitution d'alliances entre les différents partenaires sociaux. Mais les fondements d'un modèle performant tels que l'étatisme et le nationalisme civique sont devenus empreints de faiblesses et d'insuffisances que l'utilisation du concept de gouvernance permet d'identifier. Le concept se définit comme étant « la coordination efficace de l'ensemble des activités d'une entité socio-économico-politique quand les ressources, le pouvoir et l'information sont vastement distribués ». Malgré l'inefficacité décrite, il est possible de repenser le modèle québécois de développement par la construction des communautés qui s'appuie sur la régionalité et la socialité. Finalement, le renouveau s'appuierait sur une stratégie de-gouvernance pour un meilleur usage de l'intelligence collective et des cités-régions intelligentes.The article supports that it indeed had a Quebecois model of development, but it became ineffective and questioned. This model distinguished itself by his(her dynamic state interventionist and by the constitution of alliances among the various social partners. But the foundations of a successful model such as the state control and the civil nationalism became printed by weaknesses and by incapacities which the use of the concept of governance allows to identify. The concept defines itself as being « the effective coordination of all the activities of an entity « socio-économico-politique » when the resources, the power and the information are distributed spaciously » Meanwhile the described ineffectiveness, it is possible to rethink the Quebecois model of development by the construction of the communities which leans on the regionality and the sociality. Finally, the flourish would lean on a strategy

LE CORBUSIER: CONCURSOS Y PALACIOS / Le Corbusier: competitions and palaces

Directory of Open Access Journals (Sweden)

Fernando Zaparaín Hernández

2012-11-01

Full Text Available RESUMEN Cuando Le Corbusier ya había pasado de los cuarenta años se enfrentó a dos concursos internacionales: el Palacio de las Naciones en Ginebra (1926–31 y el Palacio de los Soviets en Moscú (1931–32 con los que intentaba acceder a grandes encargos de estado con mayor escala urbana en los que poner a prueba su ideario moderno sobre arquitectura y urbanismo. En ambos casos estuvo entre los vencedores pero por conveniencia e indecisión, los poderes políticos optaron por soluciones academicistas. Al conocer las decisiones definitivas, Le Corbusier y todos sus contactos del Movimiento Moderno orquestaron diversas polémicas ante los medios de comunicación y los gobernantes por entender que el progreso se veía lastrado por el triunfo de propuestas reaccionarias. Mediante el estudio de la correspondencia con personas particulares como Moser, Giedion, Colly o Stonorov, conservada en la Fundación Le Corbusier, se analizan las relaciones y el tono ideológico en torno a aquellas protestas. En esos textos quedan reflejados los principales rasgos que caracterizan la modernidad como su internacionalización, la seguridad en la propia misión, la defensa de lo nuevo o el método dialéctico. SUMMARY When Le Corbusier had already passed the age of forty he confronted two international competitions: the Palais des Nations in Geneva (1926–1931 and the Palace of the Soviets in Moscow (1931–32, with which he attempted to access large state commissions, with greater urban scale, in which to test his ideas about modern architecture and urbanism. In both cases he was among the winners, but through convenience and indecision the political powers opted for solutions from academicians. Upon knowing the final decisions, Le Corbusier and all his contacts in the Modern Movement orchestrated several controversies with the media, and the people in power, to convey that progress seemed burdened by the triumph of reactionary proposals. The relationships

Le rôle des associations  dans la médiation en archéologie

OpenAIRE

Sence, Christophe

2014-01-01

Le milieu associatif est connu en France pour son dynamisme et sa réactivité. Il en va de même en archéologie, notamment dans le domaine de la médiation. Si le public ignore bien souvent qu’une association se cache derrière le lieu qu’il vient de visiter, nombreux sont les sites archéologiques, toutes périodes confondues, dont la mise en valeur est entièrement assumée par une telle structure. Dans ce cadre, tout est envisageable, de la simple ouverture pendant les Journées européennes du patr...

Construire les stratégies avec le Balanced Scorecard:vers une approche interactive du modèle de Kaplan et Norton

OpenAIRE

Gérald Naro; Denis Travaillé

2010-01-01

(VF)L’objectif de cet article est de confronter le Balanced Scorecard avec le modèle des leviers de contrôle de Simons (1995) et de discuter de son rôle dans les différentes phases du processus stratégique. Nous privilégions une représentation du BSC comme outil de contrôle interactif. Notre recherche est fondée sur une méthodologie longitudinale de type recherche action à partir de l’étude de deux cas. Les résultats montrent que le BSC crée un processus de construction collective favorisant ...

L’économie politique du désir dans le rituel et le militantisme au SriLanka

Directory of Open Access Journals (Sweden)

Wim Van Daele

2013-03-01

Full Text Available Le désir est au cœur des interactions complexes entre le développement et la religion. Cet article examine ses différentes expressions, comme étant une des préoccupations fondamentales de nombreuses religions, qui motivent à la fois le développement et les alternatives au développement. Au SriLanka, face au changement social, la forme néolibérale et mondialisée du développement est comprise et réinterprétée à travers des idiomes et des formations locales du désir. L’économie néolibérale cultive le désir et mène à un accroissement présumé de la présence des preta (fantômes affamés et avides qui se manifestent parfois au moment de la mort d’une personne. Les fantômes affamés, en tant que formations fétichisées du désir, trouvent un écho chez les consommateurs et les entrepreneurs, qui montrent unappétit insatiable vis-à-vis d’une richesse matérielle en constante croissance. Ainsi, l’apaisement ritualisé des fantômes affamés et le militantisme social de groupes tels que le Movement for National Land and Agricultural Reform (MONLAR sont clairement liés par leur préoccupation mutuelle face à l’insécurité existentielle des êtres humains et non humains, causée par un désir excessif et déséquilibré. L’action rituelle et le militantisme social divergent toutefois dans la formulation explicite de leurs préoccupations spécifiques concernant le désir. Le rituel matérialise et condense l’angoisse liée au désir, alors que le militantisme social décrit la fétichisation du désir en termes économiques, politiques et scientifiques plus abstraits.

Juan Goytisolo: Le soi, le monde et la création littéraire

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Pablo Romero Alegría

2010-01-01

Full Text Available Reseña de la obra: Yannick Llored. Le soi, le monde et la création littéraire. Presses Universitaires du Septentrion. Villeneuve d’Ascq (Francia. 2009. 421 págs. ISBN: 978-2-75740-0089-0

Le Projet d’Ole Lando sur les Contrats

DEFF Research Database (Denmark)

Holle, Marie-Louise

2017-01-01

En 2016 le projet de recherche le plus important jusqu’à présent sur le droit nordique des contrats a pris fin et un livre, de presque 400 pages, en a marqué l’aboutissement. Le résultat du projet est un « restatement » tel qu’il existe aux États-Unis. Le Restatement porte sur les règles et les...

Le point sur le sida, l'alimentation et la nutrition | IDRC - International ...

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

14 oct. 2010 ... Selon le Programme alimentaire mondial (PAM), 22 des 30 pays à risque élevé ayant besoin d'une aide alimentaire extérieure se trouvent en Afrique subsaharienne, où de nombreux États sont aux prises avec une grave épidémie de sida. Étant donné que le VIH touche les travailleurs dans la force de ...

Le fictif et le réel dans L’Empereur et l’assassin de Chen Kaige

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Xiaomin Giafferri

2008-12-01

Full Text Available Comme tout texte historique littéraire refait l’Histoire en la manipulant, le récit filmique est doublement mensongère du fait de sa double représentation : le décor et les acteurs représentent une situation qui est la fiction, et le film lui-même représente sous forme d’images juxtaposées cette première représentation. Sans vouloir faire la part du réel et de l’imaginaire, le présent travail tente de montrer comment, dans le film L’empereur et l’assassin de Chen Kaige, l’illusion de l’authenticité s’établit à travers les mécanismes de la fictionnalisation de l’Histoire. L’observation de leur manifestation est amenée à considérer deux axes principaux : l’organisation du récit et la mise en scène des personnages.

Le point sur le sida, l'alimentation et la nutrition | CRDI - Centre de ...

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

agriculture et l'alimentation ( FAO ), Stuart Gillespie a passé six mois à étudier le lien entre le VIH/sida et la sécurité alimentaire. Il a vite compris que l'épidémie risquait d'avoir, à long terme, des répercussions désastreuses sur la ...

Le FIE 2008 fait avancer le cadre écobiosocial de l'OMS | CRDI ...

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

10 mai 2011 ... Le Programme spécial de recherche et de formation concernant les maladies tropicales (TDR) de l'OMS a élaboré le concept du champ « écobiosocial », qui combine les perspectives écologiques, biologiques et sociales « pour mieux comprendre la dynamique des maladies infectieuses à transmission ...

Le vase de Pandore

Directory of Open Access Journals (Sweden)

Nicola Panichi

2000-06-01

Full Text Available Il s’agit ici de suivre les stratégies discursives par lesquelles Érasme situe sa Lingua sous le patronage symbolique de deux mythes des plus opératoires à la Renaissance : le vase de Pandore et la tour de Babel, tous deux verrouillant le texte, l’un en guise d’incipit, l’autre d’explicit, dans un dialogue où chacun use de l’autre pour renforcer les significations et instaurer le régime sémantique du texte, tant linguistique qu’éthique. Ce sont ces jeux complexes entre différents niveaux de discours dont dépend le sens ultime de l’œuvre que cet article s’attache à saisir.Se trata de seguir aquí las estrategias discursivas mediante las cuales Erasmo sitúa su Lingua bajo el dominio simbólico de dos de los mitos más funcionales del Renacimiento: el vaso de Pandora y la torre de Babel, los cuales limitan el texto, uno a modo de íncipit, otro de excipit, en un diálogo en el que se valen el uno del otro para reforzar los significados y establecer el régimen semántico del texto, tanto lingüístico como ético. Son esos juegos complejos entre diferentes niveles de discurso, de los que depende el sentido último de la obra, que este artículo intenta captar.

Le rôle de l'information en droit des entreprises en difficulté

OpenAIRE

Ould Eba, Moussa

2013-01-01

L’information est un moyen de gestion fiable et une garantie indispensable pour la protection des intérêts des acteurs de l’activité économique. Elle joue un rôle important dans la prévention et le traitement des difficultés des entreprises. En effet, à la lumière des informations comptables, financières et sociales, les dirigeants peuvent prévenir les difficultés et prendre les décisions adaptées à la situation de l’entreprise. Toutefois, en cas de procédures collectives, le besoin de protec...

Expression of the clock gene Rev-erbα in the brain controls the circadian organisation of food intake and locomotor activity, but not daily variations of energy metabolism

NARCIS (Netherlands)

Sen, Satish; Dumont, Stéphanie; Sage-Ciocca, Dominique; Reibel, Sophie; de Goede, Paul; Kalsbeek, Andries; Challet, Etienne

2018-01-01

The nuclear receptor REV-ERBα is part of the molecular clock mechanism and is considered to be involved in a variety of biological processes within metabolically active peripheral tissues as well. To investigate whether Rev-erbα (also known as Nr1d1) in the brain plays a role in the daily variations

Le cerveau sous effet placebo

OpenAIRE

Touzet , Claude

2017-01-01

International audience; Comment le fait de croire qu’on nous injecte de la morphine (alors qu’il s’agit de sérum physiologique) peut-il faire disparaître la douleur ? Investigation sur le cerveau sous placebo.

pour le trimestre qui a pris fin le 31 décembre 2013

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

Sophie Comeau

31 déc. 2013 ... IFRS 9 – Instruments financiers. Le CNCI a l'intention de remplacer la norme IAS 39 – Instruments financiers : comptabilisation et évaluation par la norme IFRS 9. La nouvelle norme guide la classification, la comptabilisation, la décomptabilisation et l'évaluation des actifs et des passifs financiers. Le Centre ...

Protocole d'entente entre le gouvernement de l'Inde et le CRDI ...

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

22 févr. 2018 ... Ce protocole d'entente réaffirme un engagement commun envers les données probantes et l'innovation en Inde en vue de favoriser le progrès social et ... Des chercheurs appuyés par le CRDI parlent de leurs expériences au Comité sur les ONG lors du forum de la Commission de la condition de la femme.

Le médicament générique au Maroc: le point de vue du ...

African Journals Online (AJOL)

Introduction: Le médicament générique est souvent une origine de préjugés négatifs et de méfiance chez les professionnels de santé et les patients. Ceci pourrait être dû à plusieurs facteurs entre autre le manque des connaissances du patient sur ces médicaments. Le but de notre étude était d'évaluer l'information du ...

Le CRDI au Bhoutan

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

Il en résulte des solutions locales, novatrices et durables, qui offrent des choix aux personnes qui en ont le plus besoin et font changer les choses. Centre de recherches pour le développement international. CP 8500, Ottawa (Ontario) Canada K1G 3H9. Pour en savoir plus, consulter la page. Web du Bureau régional de ...

Le CRDI au Kenya

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

afin d'y favoriser la croissance et le développement. Il en résulte des solutions novatrices et durables qui ont pour but d'améliorer les conditions de vie et les moyens de subsistance. Centre de recherches pour le développement international. CP 8500, Ottawa (Ontario) Canada K1G 3H9. Pour en savoir plus, consulter.

Le genre comme rapport d’inégalité sociale dans le discours publicitaire

Directory of Open Access Journals (Sweden)

Jean-Claude Soulages

2016-12-01

Full Text Available Loin de se réduire à une simple transaction commerciale, une annonce publicitaire est un espace de croyances sur des identités, des rôles et des pratiques sociales. Au même titre que d’autres productions fictionnelles de la culture de masse, elle représente l’une des faces de ce miroir social alimenté par la circulation incessante d’attitudes et de croyances, affichant même s’il s’agit bien souvent pour cette dernière d’un positionnement ludique, un second monde peuplé par nos avatars. La publicité tout comme le fait la fiction télévisée définit l’horizon des possibles d’une communauté donnée. Ce qu’elles réalisent toutes deux c’est l’entrée de l’imaginaire dans le réel. Même si, à partir des années 70, s’opère un lent défigement des stéréotypes sexistes, le publicitaire ne se fera aucunement le porte-parole explicite d’une quelconque lutte féministe, il optera toujours pour une tactique ambivalente de double speak: des effets de décadrage mettant en exergue des situations délibérément décalées ou burlesques (Un homme qui change les couches de bébé! Un clown qui fait la lessive!, mais cristallisant des inégalités de rôles. En jouant tout à la fois sur le défigement et la réactivation des stéréotypes, c’est bien un rôle de passeur et de go between, qu’est assigné le publicitaire en se faisant l’arbitre ventriloque de ces conflits de légitimité et de construction identitaire qui agitent notre modernité.

Storicizzare le teorie psicocritiche

Directory of Open Access Journals (Sweden)

Roberto Talamo

2015-07-01

Full Text Available Le teorie psicoanalitiche della letteratura, dopo una fase di alterne fortune, sono oggi praticate da una cerchia di adepti sempre più ristretta. Le nuove koinè critico-teoriche tendono infatti a relegare la dottrina freudiana all’interno di un sapere letterario (e non interpretativo o a sostituire ad essa strumenti ritenuti più efficaci nella descrizione della sfera del mentale in letteratura (neuroestetica e neuronarratologia. La proposta storiografica che qui si avanza non vuole prendere parte in questo dibattito pro o contro la psicocritica, ma vuole leggere le proposte di teoria psicoanalitica della letteratura alla luce di una riflessione sul concetto di ibridazione, concetto sul quale queste teorie hanno costruito il loro confronto con i paradigmi teorici di volta in volta egemoni.

Novel targeted approaches to treating biliary tract cancer: the dual epidermal growth factor receptor and ErbB-2 tyrosine kinase inhibitor NVP-AEE788 is more efficient than the epidermal growth factor receptor inhibitors gefitinib and erlotinib.

Science.gov (United States)

Wiedmann, Marcus; Feisthammel, Jürgen; Blüthner, Thilo; Tannapfel, Andrea; Kamenz, Thomas; Kluge, Annett; Mössner, Joachim; Caca, Karel

2006-08-01

Aberrant activation of the epidermal growth factor receptor is frequently observed in neoplasia, notably in tumors of epithelial origin. Attempts to treat such tumors with epidermal growth factor receptor antagonists resulted in remarkable success in recent studies. Little is known, however, about the efficacy of this therapy in biliary tract cancer. Protein expression of epidermal growth factor receptor, ErbB-2, and vascular endothelial growth factor receptor-2 was assessed in seven human biliary tract cancer cell lines by immunoblotting. In addition, histological sections from 19 patients with extrahepatic cholangiocarcinoma were analyzed for epidermal growth factor receptor, ErbB-2 and vascular endothelial growth factor receptor-2 expression by immunohistochemistry. Moreover, we sequenced the cDNA products representing the entire epidermal growth factor receptor coding region of the seven cell lines, and searched for genomic epidermal growth factor receptor amplifications and polysomy by fluorescence in-situ hybridization. Cell growth inhibition by gefitinib erlotinib and NVP-AEE788 was studied in vitro by automated cell counting. In addition, the anti-tumoral effect of erlotinib and NVP-AEE788 was studied in a chimeric mouse model. The anti-tumoral drug mechanism in this model was assessed by MIB-1 antibody staining, terminal deoxynucleotidyl transfer-mediated dUTP nick end-labelling assay, von Willebrand factor staining, and immunoblotting for p-p42/44 (p-Erk1/2, p-MAPK) and p-AKT. Immunoblotting revealed expression of epidermal growth factor receptor, ErbB-2, and vascular endothelial growth factor receptor-2 in all biliary tract cancer cell lines. EGFR was detectable in six of 19 (32%) extrahepatic human cholangiocarcinoma tissue samples, ErbB-2 in 16 of 19 (84%), and vascular endothelial growth factor receptor-2 in nine of 19 (47%). Neither epidermal growth factor receptor mutations nor amplifications or polysomy were found in the seven biliary tract cancer

Le discours des Comices : un discours modèle

Directory of Open Access Journals (Sweden)

Anne Herschberg Pierrot

2009-10-01

Full Text Available Dans un discours officiel, publié par le Journal de Rouen du 22 juillet 1853, Flaubert trouve une phrase du discours des Comices qu’il avait écrite la veille. Cet article présente et reproduit les discours cités par le Journal de Rouen.In an official speech, published in the Journal de Rouen on July 22nd 1853, Flaubert found a sentence from the Agricultural association (« Comices agricoles » speeches that he had actually written himself the previous evening. This article presents and reprints the speeches quoted by the Journal de Rouen.

Le Débat des semences

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

Solutions pour les lois nationales régissant le contrôle des ressources génétiques et des ...... des pouvoirs) qui reconnaissent, dans une certaine mesure, les droits de gestion collectifs des ...... documentés, les performances physiques, etc.

Le rôle des chefs traditionnels au Ghana : un modèle inspirant ...

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

8 févr. 2011 ... Ray est également coordonnateur international du Traditional Authority ... Marketing social : le chef traditionnel acquiert une certaine expertise et ... Nadine Robitaille est rédactrice à la Division des communications du CRDI .

y ERB-2 asociados al pronóstico del cáncer de mama en la población de Barranquilla (2004- 2005

Directory of Open Access Journals (Sweden)

Luz Alba Silvera Arenas

2007-01-01

Full Text Available Objetivo: Estudiar los patrones de expresión de los receptores de estrógenos, progestagenos y erb-2 en 85 pacientes atendidas en dos laboratorios de patología de Barranquilla. De Julio del 2004 a diciembre del 2005. Material y metodos: Estudio Descriptivo de corte. Se utilizaron 85 muestras incluidas en parafina de pacientes con diagnóstico de cáncer de mama para lo cual, se realizaron estudios inmunohistoquimicos con técnicas de peroxidasa – antiperoxidasa, se utilizaron anticuerpos monoclonales Dako contra estrógenos, progestágenos y ebr-2. Resultados: Se observó carcinoma in situ (4, cáncer mesenquimal (1, carcinoma lobulillar (1 y resto carcinomas ductales infiltrantes grados I, II y III. La inmunohistoquímica mostró positividad para estrógeno y progestágeno a nivel intracelular en 73 casos y negativos para erb-2, 11 fueron negativos para estrógeno y progestágeno, uno fue positivo para ebr-2. Conclusiones: 1. El carcinoma ductal infiltrante grado II y III fue la forma histológica que se presentó con mayor frecuencia (80 casos. 2. El 88,23 % de los casos fueron estrógeno y progestágeno positivos. 3. La relación entre el componente histológico y receptores hormonales positivos, sugieren buen pronóstico.

pour le trimestre qui a pris fin le 31 décembre 2012

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

acray

31 déc. 2012 ... -24,8 %. Contributions de bailleurs de fonds. Financement de la programmation en recherche pour le développement. 39 837. 11 122. 9 044. 11 376. -20,5 %. 29 081. 25 399. 25 400. 0,0 % ..... internationales d'information financière (normes IFRS) telles que publiées par le Conseil des normes comptables ...

Le CERN ouvre ses entrailles au public

CERN Multimedia

2004-01-01

"Le CERN se lance dans une grande opération de relations publiques pour son cinquantième anniversaire. Le centre de recherche organisera une journée portes ouvertes le 16 octobre. Quelque 50 sites pourrant être visités" (1/2 page)

Le front oriental de Lille

Directory of Open Access Journals (Sweden)

Étienne Poncelet

2011-06-01

Full Text Available De la porte d’eau de la Basse Deûle jusqu’au fort Saint-Sauveur, le front oriental de Lille, fortifié à l’époque espagnole, glisse ses courtines dans les entrelacs du périphérique et des gares. L’enjeu urbain actuel consiste à s’appuyer sur ces murs historiques pour « passer malgré tout » à travers cet écheveau urbain et retisser les fils de la continuité des promenades au cœur de la ville. Moins connus que le front occidental de la reine des citadelles, ces anciens espaces militaires sont une chance pour l’urbanisme de demain dont les opérations en cours de la Porte de Gand et de la Basse Deûle témoignent déjà.The east wall, at Lille, fortified during the period of Spanish occupation, extends from the Porte d'Eau de la Basse-Deûle to the Saint-Sauveur fort. Its curtain walls emerge today in a landscape of ring roads and railway territories. The issue today is to profit from these historic walls in order to make some sense of the urban chaos and to reinstate some urban continuity in the city-centre walkways. Although they are not as well known as the western wall of this major fortified city, these former military properties are an exciting opportunity for tomorrow's town-planners, as the operations already underway at the Porte de Gand et de la Basse Deûle suggest.

Le CRDI en Jordanie

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

... dans les pays en développement afin d'y favoriser la croissance et le développement. Il en résulte des solutions novatrices et durables qui ont pour but d'améliorer les conditions de vie et les moyens de subsistance. Centre de recherches pour le développement international. CP 8500, Ottawa (Ontario) Canada K1G 3H9.

Le CRDI au Mali

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

de ces technologies et tentent de déterminer si un régime de microcrédit pourrait encourager leur adoption. On cherche par cela à accroître la sécurité alimentaire de même que le rendement des cultures de dolique, de sorgho et de mil. □ Menaces pesant sur les moyens de subsistance. Financement octroyé pour le Mali :.

L'astronomie dans le monde

Science.gov (United States)

Manfroid, J.

2008-09-01

Fragmentation et astéroïdes binaires; Astéroïde géocroiseur triple; Rosetta sort de son hibernation; Messenger; Transit lunaire vu par Deep Impact; Titan; Phobos; Phoenix; Einstein avait raison; Le ballet des taches rouges; Le poids des lentilles;

Prends soin du métro. Le contrôle-soin, forme émergente des régulations et menaces souterraines

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Yves Jouffe

2015-05-01

Full Text Available Le métro de Santiago a subi une dégradation significative de ses conditions de transport du fait de son intégration au Transantiago, le réseau de bus urbains. L’opérateur du métro a donné beaucoup de visibilité à ses dispositifs de contrôle des nouvelles masses d’usagers : barrières optimisées, signalétique omniprésente, agents démultipliés, etc. L’étude du discours officiel de l’entreprise et surtout l’observation ethnographique de ces dispositifs révèlent que les modalités de contrôle ont elles-mêmes évoluées. En plus de la menace légale exercée contre les étrangers et de la régulation des flux par une discipline des corps, un contrôle-soin s’exerce sur une population à protéger : la population qui bénéficie du soin de l’opérateur lui est redevable d’un contre-soin. Le contrôle-soin constitue non seulement une modalité émergente de contrôle mais aussi la forme générale du contrôle dans le métro de Santiago.

Le harcèlement moral au travail

CERN Document Server

Hirigoyen, Marie-France

2017-01-01

Isoler, discréditer, déconsidérer le travail rendu, intimider, insulter... Les moyens sont nombreux, les conséquences dramatiques. En France, la reconnaissance du harcèlement moral et sa condamnation juridique sont venues changer le regard que portent les salariés sur certaines situations vécues et interpeller les entreprises quant à leurs méthodes de management. Que sait-on aujourd’hui sur le harcèlement au travail ? Quels en sont les effets sur les individus, leurs proches et la société ? Comment le punir ou le prévenir ? En décortiquant les mécanismes du harcèlement, ses origines et ses conséquences ainsi que les réponses qui y sont actuellement apportées en France comme à l’étranger, cet ouvrage fait le point sur un fléau de nos sociétés narcissiques.

Le LHC, un tunnel cosmique

CERN Multimedia

CERN. Geneva

2009-01-01

Et si la lumière au bout du tunnel du LHC était cosmique ? En d’autres termes, qu’est-ce que le LHC peut nous apporter dans la connaissance de l’Univers ? Car la montée en énergie des accélérateurs de particules nous permet de mieux appréhender l’univers primordial, chaud et dense. Mais dans quel sens dit-on que le LHC reproduit des conditions proches du Big bang ? Quelles informations nous apporte-t-il sur le contenu de l’Univers ? La matière noire est-elle détectable au LHC ? L’énergie noire ? Pourquoi l’antimatière accumulée au CERN est-elle si rare dans l’Univers ? Et si le CERN a bâti sa réputation sur l’exploration des forces faibles et fortes qui opèrent au sein des atomes et de leurs noyaux, est-ce que le LHC peut nous apporter des informations sur la force gravitationnelle qui gouverne l’évolution cosmique ? Depuis une trentaine d’années, notre compréhension de l’univers dans ses plus grandes dimensions et l’appréhension de son comportement aux plus peti...

Le plurilinguisme du perroquet

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Manuel Mühlbacher

2012-05-01

Full Text Available La figure du perroquet occupe une position ambiguë face à la question de la traduction. Il est capable d’imiter des paroles en toutes les langues, mais il n’est capable d’en comprendre aucune — il ne peut que répéter des sons, c’est-à-dire des signifiants. Le traducteur semble faire le contraire quand il passe d’une langue à une autre en tâchant de transmettre une signification semblable par d’autres signes. L’article vise à discuter le rôle du traducteur et sa relation, éventuellement équivoque, au perroquet, en analysant la traduction allemande de Trois Contes par André Stoll et Cora van Kleffens. Un décalage au niveau sémantique peut éclairer l’interprétation du texte, par exemple en explicitant des allusions sous-jacentes, tandis que le transfert de la syntaxe française en allemand pose souvent des problèmes considérables. Comment le traducteur peut-il reproduire des structures syntaxiques qui n’existent pas en allemand, mais qui ne cessent de revenir dans le texte français ? Que faire si le texte se met à jouer au perroquet et finit par se singer lui-même ? André Stoll et Cora van Kleffens ont su trouver des stratégies pour affronter ces difficultés.The figure of the parrot holds an ambiguous position towards the question of translation. It is able to imitate all languages, but it will never understand any of them – its only skill is to mimic sounds, i.e. mere signifiers. On the contrary, the translator seems to be the antithesis of the parrot when he moves from one language to another. He endeavours to convey a similar meaning, but by different signs. The article aims at discussing the role of the translator and his or her eventually equivocal relation to the parrot by means of analysing the German translation of Trois Contes by André Stoll and Cora van Kleffens. Whereas a semantic divergence can result in a different tendency on the level of interpretation, as in the case of an underlying

Évaluation spatiale et prospectives sur le risque de pollution diffuse par le nitrate sur le bassin versant de la Bultière

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LE FLAHEC, François

2015-06-01

Full Text Available En France, la protection des captages d'eau potable est une préoccupation majeure : le Grenelle Environnement a identifié plus de cinq cents sites menacés par les pollutions diffuses, d'où la nécessité de mettre en place des plans d'action pour les protéger. En Vendée, dans le bassin versant de la Bultière, confronté à des rejets importants de nitrate, une étude par modélisation agronomique et hydrologique a été mise en œuvre avec le logiciel Swat, un outil alliant analyse spatiale et simulation, qui doit permettre de donner des orientations et de prioriser des solutions.

Le point sur les données ouvertes : réflexion sur leur rôle en ...

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

L'ouverture de portails gouvernementaux de données ouvertes aux États-Unis et au Royaume-Uni en 2009 a été le fer de lance d'un mouvement mondial qui, près de dix ans plus tard, a été adopté par des dirigeants du monde entier, comme le montrent les objectifs de développement durable, l'accord de Paris sur le ...

Indicadores de Prognóstico em Câncer de Mama com Axila Negativa: Receptor de Estrógeno e Expressão de P53 e de c-erbB-2 Prognostic Indicators In Lymph Node-Negative Breast Cancer: Estrogen Receptor and P53 and c-erbB-2 Protein Expression

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Adriana Harter Teixeira Bolaséll

2000-08-01

Full Text Available Objetivo: avaliar o valor prognóstico do receptor de estrógeno e da expressão das proteínas p53 e c-erbB-2 no câncer de mama com axila negativa. Métodos: foi realizado estudo imuno-histoquímico em material incluido em parafina, do arquivo do Instituto de Pesquisas Cito-Oncológicas (IPCO da Fundação Faculdade Federal de Ciências Médicas de Porto Alegre (FFFCMPA, de 50 casos de câncer de mama sem comprometimento dos linfonodos axilares, em mulheres menopausadas, tratadas na Irmandade da Santa Casa de Porto Alegre (ISCMPA e no Hospital Santa Rita de Porto Alegre (HSR de janeiro 1990 a dezembro de 1994. Para análise estatística foram utilizados os testes de c² com correção de Yates, teste exato de Fisher e curvas de sobrevida pelo método de Kaplan-Meier comparados pelo teste log rank. O seguimento médio das pacientes foi de 3,6 anos (3,1-4,5. Dos 50 casos, 14 apresentaram recidiva no período observado. Resultados: a média de idade foi 61 anos (variação de 46 a 78 anos. A mastectomia radical modificada (MRM foi realizada em 35 pacientes (70% e 15 (30% foram submetidas a setorectomia com esvaziamento axilar e posterior radioterapia. Metade das pacientes que apresentaram recidiva apresentaram-na nos três primeiros anos após o diagnóstico. O tamanho médio do tumor foi 2,8 cm (1,98-3,13 e o tipo histológico mais freqüente foi o carcinoma ductal infiltrante de tipo histológico não-especial (92%, conforme a graduação histológica de Bloom e Richardson, sendo 3 grau I (6,6%, 35 grau II (76% e 8 grau III (17,4%; nos tumores que recidivaram não houve nenhum grau I, 9 (25,7% eram grau II e 3 (37,5% eram grau III. Em relação ao prognóstico, a taxa de intervalo livre de doença foi menor quando da associação de tumor pouco diferenciado (grau III com receptor de estrógeno negativo (p = 0,006, p53 positivo (p = 0,006 e c-erbB-2 positivo (p = 0,001. Conclusão: mulheres menopausadas com câncer de mama sem comprometimento

Le massacre de la mariée

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Bastiaan van der Velden

2016-06-01

Full Text Available Le Massacre des innocents a été pour Marcel Duchamp l’une de ses sources en composant Le Grand Verre. Ce ‘massacre’ est dans ce cas plus précisément une attraction foraine. D’autre part l’infanticide à Bethlehem constitue un sujet maintes fois représenté par différents peintres. Pour Alfred Jarry, auteur littéraire et de théâtre qui a plus particulièrement inspiré Duchamp, le tableau Le Massacre des innocents de Breughel l’Ancien était une pièce clé qui lui permettait de démontrer pourquoi il rejetait l’art historisant en peinture et dans le théâtre.

Vers une plus grande collaboration régionale — le CRDI appuie le ...

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

26 janv. 2011 ... Richard Fuchs croit que les gens qui veulent comprendre comment le monde évolue devraient jeter un coup d'oeil à la vague de transformations qui déferle sur ... Bien qu'ils aient souvent de la difficulté à se démarquer face à la véritable dynamo économique qu'est la Chine, des pays tels que le Laos, ...

Peut-on voyager dans le temps ?

CERN Multimedia

CERN. Geneva

2008-01-01

La possibilité de voyager dans le temps est régulièrement évoquée par les magazines scientifiques (et parfois même par les scientifiques). Elle est également le sujet de nombreux romans de science-fiction. Nous discuterons d’abord du sens qu’on peut donner à l’expression « voyager dans le temps », puis nous expliciterons ce que la physique contemporaine dit à ce propos.

Le CRDI à la COP23 | CRDI - Centre de recherches pour le ...

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

En collaboration avec ses bénéficiaires et partenaires, le CRDI anime et participe à une série d'activités et d'événements durant la COP23, y compris des événements parallèles officiels de la CCNUCC et des groupes d'experts, des groupes de discussion, des ateliers et la 15e édition des Journées sur le développement et ...

Le rôle du récit de vie dans le discours politique de Lula The role of Lula’s Life Story in his Political Speeches

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Ida Lucia Machado

2011-10-01

Full Text Available Cet article propose une réflexion sur le rôle du récit de vie dans les discours politiques, et plus précisément dans les discours d’investiture à la présidence du Brésil de Luis Ignacio Lula da Silva. Il analyse quelques fragments qui mêlent expressément des souvenirs de sa vie passée aux discours politiques d’actualité, mais aussi qui font allusion à sa vie de façon indirecte. Dans le premier discours, Lula se présente comme un personnage de l’histoire, un « il » qui veut travailler pour la collectivité ; néanmoins, les allusions à sa trajectoire de vie le légitiment comme celui qui peut promouvoir le changement requis par le peuple. Dans le second discours, Lula utilise depuis le début un « je » ancré dans sa propre histoire : sa « petite » histoire personnelle semble ainsi s’incorporer à la « grande » histoire d’une nation. En ce sens, le récit de vie comprend une dimension argumentative qui permet de construire un ethos présidentiel par le jeu qu’il instaure entre l’individuel et le collectif, créant ainsi un effet de pathos qui appelle à l’identification. On s’interroge dans ce cadre sur la question du populisme dans son rapport aux stratégies de captation propres au discours politique.This paper analyzes fragments of President Luiz Inácio Lula da Silva’s inaugural speeches. Lula da Silva served as the President of Brazil for two consecutive terms in office. In his first inaugural speech, Lula da Silva refers to himself as a historical character, and uses the pronoun “he” (or “not-I”, a “he” at the service of the community. However, his path in life, mentioned in a single paragraph, legitimizes him as someone who is able to bring forward the changes demanded by the people. From the beginning of his second inaugural speech, Lula da Silva uses the pronoun “I”, which points to his own story: therefore, his “small, personal story” seems to be embedded into the

Le CRDI en Afghanistan

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

Depuis près de 40 ans, le CRDI collabore étroitement avec les chercheurs des pays en développement et les appuie dans leur quête de moyens de créer des sociétés en meilleure santé, plus équitables et plus prospères. Centre de recherches pour le développement international. CP 8500, Ottawa (Ontario) Canada K1G ...

Osteossarcomas humanos de alto grau: imunoexpressão de p53, erb-2 e P-glicoproteína, e correlação com o parâmetro anaplasia P-glycoprotein, erb2 and p53 expression in high-grade human osteosarcomas and their correlation with anaplasia

OpenAIRE

Maria Teresa de Seixas Alves; Luciana Nakao Odashiro Miiji; Larissa Cardoso Marinho; Antonio Sergio Petrilli; Reynaldo Jesus-Garcia; Silvia Caminada Tolledo; Francy Reis da Silva Patricio

2008-01-01

INTRODUÇÃO: Osteossarcoma (OS), o mais freqüente tumor primário maligno do osso, tem comportamento local agressivo e alto índice de disseminação sistêmica. Os eventos que permitem o crescimento e a disseminação tumoral ainda permanecem controversos. Os estudos sobre a carcinogênese e a progressão dessa neoplasia, com base na imunoexpressão de c-erb-B2, P-glicoproteína (P-gp) e p53, apresentam resultados conflitantes acerca do real valor prognóstico e suas correlações com parâmetros histológic...

Equazioni: le icone del sapere

NARCIS (Netherlands)

Bais, S.

2009-01-01

Il mistero del cosmo è scritto nel linguaggio della matematica, e le equazioni sono le frasi che ne esprimono la bellezza e la profondità. Cercare di spiegare la scienza senza equazioni è come cercare di spiegare l’arte senza illustrazioni: partendo da questo presupposto, Sander Bais presenta una

La culture matérielle enfantine entre le cute et le cool

Directory of Open Access Journals (Sweden)

Gilles Brougère

2012-11-01

Full Text Available Cet article explore la façon dont on adresse un objet à l’enfant, c’est-à-dire la rhétorique à l’œuvre pour séduire les enfants (et les parents dans certains cas. Si l’éducation peut être présente pour certains produits, domine très largement aujourd’hui une rhétorique du fun, une association de l’objet à l’enfance via le divertissement et l’insertion dans une culture des pairs. Pour partie cet adressage se fait à travers l’utilisation de personnages ou d’univers sous licence qui proposent une rhétorique du fun prête à l’emploi. Mais l’analyse des univers disponibles montre que l’on peut décomposer le fun à travers deux pôles opposés, le cute, dont Hello Kitty constitue un exemple archétypal, et le cool, que Titeuf permet de saisir dans sa logique. A travers la distinction du cute et du cool, il s’agit de contribuer à l’analyse du déploiement contemporain d’une culture du divertissement qui est incorporée aux objets de l’enfance, tout en étant un moyen de capter l’intérêt de ceux-ci.

On Leśniewski’s Characteristica Universalis

NARCIS (Netherlands)

Betti, A.

2010-01-01

Leśniewski's systems deviate greatly from standard logic in some basic features. The deviant aspects are rather well known, and often cited among the reasons why Leśniewski's work enjoys little recognition. This paper is an attempt to explain why those aspects should be there at all. Leśniewski

Le déficit de filles

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

de la population est une tendance plus récente. C. Le déficit de filles. Le déséquilibre du ratio hommes-femmes en Inde. D. R. O. I. T. S. D. E. S. F. E. M. M. E. S. E. T. P. A. R. T. IC. I. P. A. T. IO. N. C. I. T. O. Y. E. N. N. E. CENTRE DE. RECHERCHES. POUR LE. DÉVELOPPEMENT. INTERNATIONAL. CRDI : Jason Taylor ...

Le vide univers du tout et du rien

CERN Document Server

Diner, Simon

1997-01-01

Pourquoi l'Univers plutôt que le vide ? Le temps et l'espace existent-ils en l'absence de l'Univers ? Que reste-t-il quand tout est enlevé ? Pourquoi quelque chose plutôt que rien ? Depuis des siècles, ces interrogations mobilisent philosophes et physiciens. Mais aujourd'hui, le vide n'est pas le rien. Il serait même l'acteur central de l'histoire de la matière et de l'Univers, le partenaire privilégié de la physique. Vide et matière ne sont plus deux manifestations séparées de la nature, mais deux aspects d'une même réalité. Le vide est l'état de base dont la matière émerge, sans couper son cordon ombilical Le vide comme Univers du rien cède la place au vide comme Univers du tout. Que le vide puisse être conçu par les physiciens comme réservoir potentiel d'univers, voici qui ne devrait laisser personne indifférent. Ce livre ouvre un débat et nous convie à une réflexion surprenante.

Le charme slave

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Antonella Mauri

2012-09-01

Full Text Available Antonella Mauri analyse l’image des femmes slaves immigrées en Italie telle qu’elle apparaît à travers la publicité, la littérature romanesque (La ballata dei lavavetri de Peter Del monte, Luce Profuga de Valerio Aiolli, Pornokiller de Bruno Ventavoli, le cinéma, la bande dessinée (Danilo Maramotti, image qu’elle oppose aux résultats d’une enquête qu’elle a menée sur le terrain. Elle s’interroge en particulier sur la permanence des stéréotypes liés à la femme slave.

Le matérialisme scientifique

Science.gov (United States)

Meunier, Jean-François

2004-03-01

De nos jours, il arrive quotidiennement aux grands hommes d'avoir à fréquenter d'ignorants mortels épris d'une conviction maladive que la science est la grande responsable de tous les maux du monde. Évidemment sans physique atomique, il n'y aurait pas eu d'Hiroshima et sans révolution industrielle, pas de pollution et etc. Cependant, ces accusations envers le progrès technique sont tout à fait injustes, irréfléchies et, j'irai même jusqu'à dire, irresponsables, puisque le calcul, i.e. la planification, même la plus élémentaire, est ce qui caractérise le mieux, pragmatiquement, la société humaine. À mon avis, les problèmes sociaux tireraient plutôt leur origine de sciences sociales irréalistes, qui, concrètment, inspireraient ou serviraient d'alibis à ceux qui détiennent véritablement le pouvoir. Dans cet article, je tenterai donc de démontrer la meilleure véracité et efficacité du matérialisme scientifique. Cette doctrine, dont Mario Bunge est le plus illustre représentant, s'appuy sur les résultats théoriques et expérimentaux des sciences factuelles ainsi que sur l'exactitude logique des mathématiques, utilisées ici comme langage universel de l'expression des idées. Cette conception philosophique qui s'inspire principalement du modèle des théories physiques, stipule que les réalités sociales sont, comme tout autre réalité, matérielles, mathématisables et représentables comme des systèmes en interaction. En fait, le modèle des physiciens ayant historiquement fait ses preuves en matière de testabilité et de cohérence interne est proposé d'être appliquer aux sciences sociales, aujourd'hui scindées des sciences dites pures sous l'inspiration des pseudo penseurs néo-kantiens, phénoménologiques et post-moderne. Cette nouvelle approche permettrait ainsi d'évoluer plus exactement vers une compréhension des bases sociales et biologiques du comportement humain afin de développer une éthique sans cesse plus r

Le Corbusier’s Dioramas

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José Ramón Alonso Pereira

2013-10-01

Full Text Available AbstractLe Corbusier symbolizes the modern rational urbanism, whose rigorous effort of town planning demands a parallel effort of comprehension. It opposes to these contemporary urbanism that wish to perceive and to enjoy cities in a sensible way. Nevertheless, sentiment and reason are not adverses and Le Corbusier gives us at his  moment keys to intent a synthesis, joined them in a singular way by means of his ‘boîtes à miracles’ or ‘magic boxes’: those "architectural spectacles of synthesis" that he defined in 1951 Ciam. Here we try to approach to the first of those ‘spectacles’: the ‘diorama’, considering it as a corbusean strategy of mediation between rational and sensible in modern and contemporary city.Key wordsLe Corbusier, diorama, Ville Contemporaine, Plan Voisin, Plan Maciá

Conception d’un automate cellulaire non stationnaire à base de graphe pour modéliser la structure spatiale urbaine: le modèle Remus

Directory of Open Access Journals (Sweden)

Arnaud Banos

2007-10-01

Full Text Available Nous proposons dans cet article une formalisation originale des automates cellulaires géographiques, à même de mieux prendre en compte grâce à une structure de graphe le voisinage irrégulier et dynamique d’entités spatiales. Le modèle Remus permet ainsi de représenter sous la forme d’un graphe mathématique les entités spatiales du bâti et les réseaux de transport urbain (graphe urbain ; il permet aussi de calculer la distance-temps entre bâtiments par le réseau. Le modèle Remus permet l’extraction de différents graphes, dont le graphe fonctionnel des distances-temps entre les immeubles et le graphe de relations de voisinage qui représente le voisinage par le réseau pour un certain seuil de temps de trajet et pour un mode de transport donné.

Model-based investigation of the circadian clock and cell cycle coupling in mouse embryonic fibroblasts: Prediction of RevErb-α up-regulation during mitosis.

Science.gov (United States)

Traynard, Pauline; Feillet, Céline; Soliman, Sylvain; Delaunay, Franck; Fages, François

2016-11-01

Experimental observations have put in evidence autonomous self-sustained circadian oscillators in most mammalian cells, and proved the existence of molecular links between the circadian clock and the cell cycle. Some mathematical models have also been built to assess conditions of control of the cell cycle by the circadian clock. However, recent studies in individual NIH3T3 fibroblasts have shown an unexpected acceleration of the circadian clock together with the cell cycle when the culture medium is enriched with growth factors, and the absence of such acceleration in confluent cells. In order to explain these observations, we study a possible entrainment of the circadian clock by the cell cycle through a regulation of clock genes around the mitosis phase. We develop a computational model and a formal specification of the observed behavior to investigate the conditions of entrainment in period and phase. We show that either the selective activation of RevErb-α or the selective inhibition of Bmal1 transcription during the mitosis phase, allow us to fit the experimental data on both period and phase, while a uniform inhibition of transcription during mitosis seems incompatible with the phase data. We conclude on the arguments favoring the RevErb-α up-regulation hypothesis and on some further predictions of the model. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Faire la chose « la plus sensée » pour le Canada et pour le monde ...

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

18 déc. 2014 ... Je faisais partie de la délégation qui a accompagné dernièrement le gouverneur général du Canada, Son Excellence le très honorable David Johnston, et Son Excellence Sharon Johnston au ... Il avait ensuite a déclaré que ce que le CRDI a fait au Chili, c'est qu'il a permis aux idées de continuer de vivre.

[FR] Le developpment du Travail Social et le pluralisme au Québec

Directory of Open Access Journals (Sweden)

André Jacob

2011-06-01

Full Text Available Normal 0 21 false false false ES X-NONE X-NONE MicrosoftInternetExplorer4 Au Canada et au Québec, traiter des questions liées à la diversité culturelle et au racisme a été un défi pour les gouvernements depuis les années soixante. Auparavant et jusqu'à présent, une grande partie des responsabilités en termes de développement ethnoculturel sensible des services publics (services sociaux, des programmes de formation en travail social, etc. ont été laissés aux mains d’organismes de charité non-lucratifs. Cependant, peu à peu, depuis les années soixante, le gouvernement fédéral et le gouvernement provincial, ont dû développer des politiques et des programmes d'action. Au Québec, le travail social a fait partie du débat face à deux grands courants politiques, l’un canadien basé sur le multiculturalisme, et l’autre québécois basé sur l'interculturalisme. L'article vise à donner une perspective historique

L'espace, un outil de contrôle ? : Le cas Pont-à-Mousson (1921-190

OpenAIRE

Labardin, Pierre

2011-01-01

Cet article s'intéresse aux impacts des open space en matière de contrôle à partir d'un travail historique. Nous nous demandons si l'espace de travail peut constituer un outil de contrôle opérationnel. Dans une première partie, nous proposons une définition historique des espaces travail qui nous amène à justifier notre méthodologie de recherche historique. Nous travaillons à partir des archives des années 1920 de la société Pont-à- Mousson. Nous présentons longuement le contexte de la mise e...

Révolution tunisienne et Internet : le rôle des médias sociaux

OpenAIRE

Lecomte, Romain

2013-01-01

Suite au mouvement de contestation populaire qui a conduit à la chute du régime de Ben Ali, médias et experts des NTIC ont beaucoup insisté sur le rôle révolutionnaire joué par Internet en Tunisie, et plus particulièrement par les « réseaux sociaux ». Dans cet article, tout en cherchant à analyser comment, concrètement, les usages d’Internet ont pu servir de catalyseur au mouvement de contestation né à Sidi Bouzid, nous mettons en garde contre certaines analyses en vogue véhiculant le mythe d...

Le déficit de filles — Le déséquilibre du ratio hommes-femmes en Inde

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

Plusieurs acteurs, dont le journal national indien The Hindu, ont qualifié ce brusque ... Voilà pourquoi le Centre de recherches pour le développement international ... De nouvelles tendances, comme la limite de deux enfants par famille, .... les professionnels de la santé et d'abolir les initiatives favorisant la stérilisation.

Droits d'auteur | CRDI - Centre de recherches pour le ...

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

Droits d'auteur détenus par le CRDI Sauf indication contraire, les droits d'auteur relatifs aux documents mis en ligne sur le présent site Web sont détenus par le Centre de recherches pour le développement international (CRDI).

Le Combat de l’amour divin et de l’amour profane : un ballet de Charpentier pour le collège d’Harcourt

OpenAIRE

Demeilliez , Marie

2014-01-01

International audience; De l’activité de Marc-Antoine Charpentier au service des jésuites, nous sont parvenus un vaste répertoire religieux ainsi que le célèbre « opéra chrétien » David et Jonathas (1688), l’une des rares partitions composées pour le collège Louis-le-Grand qui soit conservée. Alors que le musicien en fut le maître de musique pendant plusieurs années, l’on sait peu de choses de sa participation aux somptueuses représentations théâtrales dont le collège s’est fait une spécialit...

La preuve par le nombre

Directory of Open Access Journals (Sweden)

Hélène Verdier

2012-04-01

Full Text Available S’il en était besoin, la question des usages et de la finalité des résultats de l’inventaire général pourrait être abordée par le nombre : nombre d’œuvres répertoriées, de communes inventoriées, de clichés photographiques réalisés, de dossiers, de consultations des notices dans les bases de données… Les additions aujourd’hui sont éloquentes, mais elles laissent dans l’ombre le rôle de l’inventaire qui, en mettant en œuvre une démarche systématique de connaissance, participe à l’ identificatio...

Le bord de la solitude

Directory of Open Access Journals (Sweden)

Jean-Paul Galibert

2010-04-01

Full Text Available La solitude a un bord, et non un seuil, parce que sinon, ce ne serait pas la solitude. Car le seuil a ceci de merveilleux qu’il sépare un dedans et un dehors, en sorte qu’il reste franchissable, et que l’on peut toujours sortir, et rentrer à sa guise. De ce fait, où que soient les autres, le seuil garantit donc que je pourrais les rejoindre, et me délasser, en changeant de lieu, des inconvénients croisés de l’intérieur et de l’extérieur. Dans le seuil, la métaphore implicite de la maison nous...

Leïomyosarcome de la prostate: Neoplasie rare

Directory of Open Access Journals (Sweden)

D. Basraoui

2012-03-01

La TDM et surtout l'IRM jouent un rôle primordial dans le bilan d'extension locale et à distance du léïomyosarcome prostatique et le seul moyen pour affirmer le diagnostic est l'histologie complétée par une étude immuno-histochimique. Leur prise en charge thérapeutique n'est pas codifiée à l'heure actuelle et leur pronostic reste très sombre.

Le mur intrapsychique chez le sujet métissé

Directory of Open Access Journals (Sweden)

Sonia Gérard

2010-06-01

Full Text Available Dans le contexte d’un couple culturellement mixte, la formation du couple implique un traitement des frontières interculturelles. De même que la naissance des enfants induisant une possible activation du processus du métissage, agit sur ces murs interculturels. Ainsi le paradigme du mur a une réelle fonction heuristique en ce qu’il permet de modéliser divers phénomènes psychiques par la constitution de représentations faisant intervenir la vision et le toucher. Nous nous sommes appuyés sur les fonctions du mur de Berlin pour comprendre notamment les phénomènes de clivage et sa résolution.In the field of mixed couples, the very formation of the couple implies intercultural borders. The birth of children, which activates the “mixing” process, may have a possible effect on these borders which are often represented as walls. Therefore the wall paradigm has a very heuristic function insofar as it allows the modelization of psychical phenomenon through representations using vision and touch. This paper considers various functions of the Berlin wall in order to understand processes such as cleaving and its resolution.

Le rapport Coopération pour le développement de l'OCDE souligne ...

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

14 févr. 2018 ... Cette 55e édition du rapport Coopération pour le développement fournit une analyse exhaustive des contraintes liées aux données auxquelles les pays en développement sont confrontés de nos jours, ainsi que des options stratégiques visant à compiler de meilleures statistiques pour le développement ...

Quel contrôle de gestion pour les startups ?

OpenAIRE

Meyssonnier , François

2015-01-01

Une étude de huit PME fondées sur la science permet d’identifier les spécificités du contrôle de gestion des startups. Dans les startups émergentes le dirigeant n’utilise que des linéaments de contrôle de gestion essentiellement pour développer son approche cognitive du business model. Dans les startups en croissance le contrôle de gestion a un rôle de garde-fou et les outils de pilotage de la performance sont utilisés essentiellement de façon interactive et pour la prévision. Les principaux ...

Les enjeux du modèle standard

CERN Document Server

CERN. Geneva

2008-01-01

Toute la matière visible dans l'Univers est décrite par le « Modèle Standard ». Selon cette théorie, la matière est constituée d'atomes, qui contiennent des électrons orbitant autour de noyaux, dont les composants fondamentaux sont les quarks. Quatre forces fondamentales agissent entre ces particules élémentaires : les forces électromagnétique est gravitationnelle, et les interactions nucléaires forte et faible. La description fournie par le Modèle Standard de ces particules et de leurs interactions est en parfait accord avec les expériences. Néanmoins, des questions fondamentales restent sans réponse jusqu'à maintenant : d'où vient la masse des particules ? Pourquoi y a-t-il tant de types de particules ? Existe-t-il une théorie unifiée de toutes les interactions ? Quelle est la nature de la matière cachée prédite par les astrophysiciens ? Le LHC au CERN donnera des éléments de réponse à ces questions au-delà du Modèle Standard.

Le patrimoine astronomique provençal

Science.gov (United States)

Rous, M.; Figon, P.; Guyot, S.

2012-12-01

L'OSU OAMP/Institut Pythéas porte les missions de conservation, inventaire et valorisation du patrimoine. Suite à la fusion de l'Observatoire de Marseille et du Laboratoire d'Astronomie Spatiale en 2000 pour créer le Laboratoire d'Astrophysique de Marseille, le déménagement des équipes sur le site de Château-Gombert en 2008 a soulevé le problème du devenir des collections des deux sites d'origine. Nous ferons le bilan des actions passées en matière de conservation et de valorisation de ce riche patrimoine : versement à l'inventaire général du Ministère de la Culture, classement de 22 instruments au titre des Monuments Historiques, inventaire et numérisation des archives anciennes, montage d'expositions et réalisation du catalogue Telescopium, 400 ans de lunettes et de télescopes. Nous présenterons les actions en cours: mesures de conservation préventive, inventaire des archives et des instruments. Nous parlerons enfin des projets: création d'un espace d'exposition permanente, participation à des expositions temporaires.

Publications | Page 17 | CRDI - Centre de recherches pour le ...

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

Publication du rapport de BSR sur le travail des enfants en Birmanie. Le CRDI finance plusieurs projets de recherche sur les facteurs expliquant le travail des enfants, incluant le rapport intitulé 'Child labor in Myanmar's Garment Sector' écrit récemment par l'organisme Business for Social Responsibility (BSR).

Savoir gérer le mal

Directory of Open Access Journals (Sweden)

Michel Maffesoli

2015-09-01

Full Text Available Le sens commun, conservatoire immémorial de la sagesse humaine « sait », de savoir incorporé, que le mal, l’ombre, la mort, la douleur sont des caractéristiques essentielles de l’existence en son entièreté. Dès lors les créatures quelles qu’elles soient, sont des manifestations de la vie et, dès lors, méritent une attitude « compassionnelle », fraternelle, parce qu’ensemble elles constituent le flux vital. C’est ainsi que l’on peut comprendre l’utilité sociale de ces divers « mondes intermédiaires » que sont les croyances, religieuses ou philosophiques, au « double », au « daimon », aux esprits et autres figures tutélaires ou effrayantes. Elles aident à vivre, au jour le jour, la souffrance en la communalisant.

L'analyse des risques l'expert, le décideur et le citoyen

CERN Document Server

Chevassus-au-Louis, Bernard

2007-01-01

Selon le modèle "standard" d'analyse du risque, utilisé majoritairement aujourd'hui, les experts basent leurs pratiques sur des hypothèses, des concepts, voire des valeurs implicites qui ne peuvent être considérées comme des évidences. La fin du XXe siècle a marqué une crise de l'expertise. Progressivement s'est instauré un débat autour du principe de précaution, principe dont l'application a des conséquences pour la décision et pour l'évaluation du risque lui-même. De son côté, la société civile a un rôle participatif fort à jouer. Se dessinent ainsi les contours d'une analyse de risque "postmoderne", dite "constructiviste", qu'il s'agit de mettre à l'épreuve concrètement.

Le Parti paysan d’union sociale

OpenAIRE

Bensoussan, David

2015-01-01

La fondation, le 11 juillet 1945 à Paris, du Parti paysan n’a sans doute guère suscité l’attention des contemporains alors immergés dans le contexte tumultueux de l’immédiat après-guerre. Il faut d’ailleurs attendre la parution, quelque temps plus tard, le 6 octobre, du premier numéro de L’Unité Paysanne, organe hebdomadaire de cette nouvelle formation politique, pour que sa naissance soit publiquement officialisée. Sans vouloir surévaluer l’importance d’une organisation qui n’arrivera jamais...

Le primitif et le mystique chez Lévy-Bruhl, Bergson et Bataille.

Directory of Open Access Journals (Sweden)

Frédéric Keck

2004-04-01

Full Text Available L’assimilation du fou, du primitif et de l’enfant a été souvent analysée comme une opposition de l’archaïque par rapport au civilisé ou du normal par rapport au pathologique. On veut montrer ici que le mystique s’ajoute à cette liste, celle-ci désignant alors plutôt des figures de l’altérité qui défient la raison. On étudie alors les liens entre la figure du primitif et celle du mystique dans la sociologie de Lévy-Bruhl, la métaphysique de Bergson et la pratique littéraire de Bataille. Par-delà les divergences entre ces trois œuvres, on montre que le lien entre primitif et mystique vise à élargir le champ de l’expérience en l’ouvrant à une altérité radicale, et en même temps prépare le terrain pour cette expérience vide et formelle que pensera le structuralisme.French human sciences at the beginning of the 20th century used to assimilate the figures of the mad person, the primitive and the child. The Author shows that this assimilation should not be interpreted in the sense of an opposition between the archaic and the developed, or the normal and the pathological, but, once the figure of the mystic is added to this list, in the sense of an opposition between rationality and its other. Three examples allows to analyse the link between the figures of the primitive and the mystic : the sociology of Lévy-Bruhl, the metaphysics of Bergson, the literature of Bataille. Through the reading of these three works, the Author shows that the link between the figures of the primitive and the mystic allows to think a larger experience by opening it to an alterity, and at the same time prepares the ground for an empty and formal experience that will be explored by structuralism.

Effet du stress salin sur le comportement physiologique et ...

African Journals Online (AJOL)

SARAH

30 juin 2013 ... rapidement dans les feuilles à partir de 25 mmol de NaCl. Le rapport de sélectivité K+/Na+ a été plus discriminant entre les variétés : Midass a présenté le rapport de sélectivité le plus élevé et Nabeul le rapport de sélectivité le plus faible. Conclusion et application : La variété Nabeul qui est de type piment ...

Le Recul de la Forêt au Viet Nam

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

Le fait d'ignorer la réalité pragmatique dans un souci d'opportunisme politique ne ... Si le texte de l'étude que voici a été rédigé en solo, les choses ont été fort différentes sur ..... Parmi les ressources requises par le système mondial — mis en place par les .... Les guerres dont le Viet Nam a été le théâtre au cours du dernier ...

Le rôle des universités africaines dans l'innovation au service du ...

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

Un nouveau réseau de recherche s'intéressera aux façons dont les universités africaines peuvent contribuer à stimuler l'innovation sur le continent noir. Le projet de recherche permettra d'examiner dans quelle mesure les universités favorisent les innovations qui contribuent à l'insertion économique des populations ...

Protein-Trap Insertional Mutagenesis Uncovers New Genes Involved in Zebrafish Skin Development, Including a Neuregulin 2a-Based ErbB Signaling Pathway Required during Median Fin Fold Morphogenesis.

Directory of Open Access Journals (Sweden)

Stephanie E Westcot

Full Text Available Skin disorders are widespread, but available treatments are limited. A more comprehensive understanding of skin development mechanisms will drive identification of new treatment targets and modalities. Here we report the Zebrafish Integument Project (ZIP, an expression-driven platform for identifying new skin genes and phenotypes in the vertebrate model Danio rerio (zebrafish. In vivo selection for skin-specific expression of gene-break transposon (GBT mutant lines identified eleven new, revertible GBT alleles of genes involved in skin development. Eight genes--fras1, grip1, hmcn1, msxc, col4a4, ahnak, capn12, and nrg2a--had been described in an integumentary context to varying degrees, while arhgef25b, fkbp10b, and megf6a emerged as novel skin genes. Embryos homozygous for a GBT insertion within neuregulin 2a (nrg2a revealed a novel requirement for a Neuregulin 2a (Nrg2a-ErbB2/3-AKT signaling pathway governing the apicobasal organization of a subset of epidermal cells during median fin fold (MFF morphogenesis. In nrg2a mutant larvae, the basal keratinocytes within the apical MFF, known as ridge cells, displayed reduced pAKT levels as well as reduced apical domains and exaggerated basolateral domains. Those defects compromised proper ridge cell elongation into a flattened epithelial morphology, resulting in thickened MFF edges. Pharmacological inhibition verified that Nrg2a signals through the ErbB receptor tyrosine kinase network. Moreover, knockdown of the epithelial polarity regulator and tumor suppressor lgl2 ameliorated the nrg2a mutant phenotype. Identifying Lgl2 as an antagonist of Nrg2a-ErbB signaling revealed a significantly earlier role for Lgl2 during epidermal morphogenesis than has been described to date. Furthermore, our findings demonstrated that successive, coordinated ridge cell shape changes drive apical MFF development, making MFF ridge cells a valuable model for investigating how the coordinated regulation of cell polarity

Protein-Trap Insertional Mutagenesis Uncovers New Genes Involved in Zebrafish Skin Development, Including a Neuregulin 2a-Based ErbB Signaling Pathway Required during Median Fin Fold Morphogenesis.

Science.gov (United States)

Westcot, Stephanie E; Hatzold, Julia; Urban, Mark D; Richetti, Stefânia K; Skuster, Kimberly J; Harm, Rhianna M; Lopez Cervera, Roberto; Umemoto, Noriko; McNulty, Melissa S; Clark, Karl J; Hammerschmidt, Matthias; Ekker, Stephen C

2015-01-01

Skin disorders are widespread, but available treatments are limited. A more comprehensive understanding of skin development mechanisms will drive identification of new treatment targets and modalities. Here we report the Zebrafish Integument Project (ZIP), an expression-driven platform for identifying new skin genes and phenotypes in the vertebrate model Danio rerio (zebrafish). In vivo selection for skin-specific expression of gene-break transposon (GBT) mutant lines identified eleven new, revertible GBT alleles of genes involved in skin development. Eight genes--fras1, grip1, hmcn1, msxc, col4a4, ahnak, capn12, and nrg2a--had been described in an integumentary context to varying degrees, while arhgef25b, fkbp10b, and megf6a emerged as novel skin genes. Embryos homozygous for a GBT insertion within neuregulin 2a (nrg2a) revealed a novel requirement for a Neuregulin 2a (Nrg2a)-ErbB2/3-AKT signaling pathway governing the apicobasal organization of a subset of epidermal cells during median fin fold (MFF) morphogenesis. In nrg2a mutant larvae, the basal keratinocytes within the apical MFF, known as ridge cells, displayed reduced pAKT levels as well as reduced apical domains and exaggerated basolateral domains. Those defects compromised proper ridge cell elongation into a flattened epithelial morphology, resulting in thickened MFF edges. Pharmacological inhibition verified that Nrg2a signals through the ErbB receptor tyrosine kinase network. Moreover, knockdown of the epithelial polarity regulator and tumor suppressor lgl2 ameliorated the nrg2a mutant phenotype. Identifying Lgl2 as an antagonist of Nrg2a-ErbB signaling revealed a significantly earlier role for Lgl2 during epidermal morphogenesis than has been described to date. Furthermore, our findings demonstrated that successive, coordinated ridge cell shape changes drive apical MFF development, making MFF ridge cells a valuable model for investigating how the coordinated regulation of cell polarity and cell shape

Publications | Page 200 | CRDI - Centre de recherches pour le ...

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

Le CRDI collabore avec les chercheurs et les établissements des pays en développement au renforcement des capacités locales par le truchement du financement, de la mise en commun des connaissances et de la ... Le partage de l''information et des techniques de la communication favorise le développement durable.

Publications | Page 103 | CRDI - Centre de recherches pour le ...

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

Le FIE 2008 fait avancer le cadre écobiosocial de l'OMS. Le Programme spécial de recherche et de formation concernant les maladies tropicales (TDR) de l'OMS a élaboré le concept du champ « écobiosocial », qui combine les perspectives écologiques, biologiques et sociales « pour mieux.

Une approche écosanté pour le contrôle de la fièvre de la vallée du ...

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

17 août 2016 ... Ces conclusions sont particulièrement pertinentes à la lumière des avancées récentes réalisées pour le vaccin contre la fièvre de la vallée du Rift et seront un important facteur à prendre en compte pour le moment de lancer le futur vaccin et la manière de le faire. Les tendances de mobilité du bétail ...

Le limus rédempteur de Andrej Tarkovski

Directory of Open Access Journals (Sweden)

Paolo Mottana

2015-04-01

Full Text Available Le cinéma de Tarkovski est riche de présences symboliques. L'essai rend, à travers le contact prolongé et fidèle aux différentes oeuvres du metteur en scène russe, la constellation de ses éléments archetipiques et de ses figures les plus significatives. Le dialogue terre-eau, le travail du feu, la récurrence de l'arbre, du bois, de l'enfance, le flux lent du temps, la phenomenologie poétique de la maison. Dans le cinéma de Tarkovski on se perd, son oeuvre, un vrai opus magnus alchimique, est un voyage dans la survivance d'un halètement mystique profondément incarné dans la matière terrestre. Son parcours circulaire, de l'arbre brûlé d'Ivan à ce qui renaît à la fin du Sacrifice miraculeusement, c'est une cheville fondamentale pour pouvoir expérimenter la puissance de l'imagination créatrice quand encore elle est l' expression d'une sensibilité inspirée à l'âme du monde".

Amélioration des moyens de subsistance agropastoraux dans le ...

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

Le CRDI lance un nouveau projet dans la région de l'ANASE. L'honorable Chrystia Freeland, ministre du Commerce international, a annoncé le lancement d'un nouveau projet financé par le Centre de recherches pour le développement international (CRDI). Voir davantageLe CRDI lance un nouveau projet dans la région ...

Gestion du Centre | CRDI - Centre de recherches pour le ...

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

Le Comité de gestion du Centre (CGC) est composé des membres de la haute direction du CRDI, notamment les directeurs de nos quatre bureaux régionaux et de nos principaux secteurs de programme. Le CGC travaille en collaboration avec le président afin de soutenir la recherche pour le développement, lui fournissant ...

Le travesti dans le théâtre du xixe siècle : une distribution à contre-genre ?

OpenAIRE

Khoury, Camille

2018-01-01

Quelques-unes des actrices les plus célèbres du xixe siècle ont laissé à la postérité le souvenir de leurs rôles travestis. C’est notamment le cas de Virginie Déjazet – au point que le déjazet est rapidement devenu synonyme de rôle travesti – ou encore de Sarah Bernhardt. Le travesti est alors un spectacle commun sur les scènes académiques françaises – tandis que certains rôles sont écrits pour être joués en travesti, de grandes actrices s’emparent de rôles masculins pour confronter leur géni...

Le Cercle de vie : l'agriculture biologique au Mexique | CRDI ...

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

13 juil. 2011 ... Le marché, Le Círculo de producción y consumo responsable [le Cercle ... En 2001, le Centre de recherches pour le développement international (CRDI) a financé ... provenant du calcaire utilisé dans l'ancien mode de transformation du ... Droits d'auteur · Éthique de la recherche · Politique de libre accès ...

J'ai le plaisir de vous présenter le quatrième rapport annuel du ...

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

ACCA

savoir autochtone en matière de prévisions météorologiques. ... Le rapport comporte en outre une carte des liens tissés par nos partenaires de recherche avec les décideurs aux échelles locale, nationale et régionale dans le cadre des efforts.

Le paysage anglais: du jardin à la campagne

Directory of Open Access Journals (Sweden)

Gilly LEHMANN

1987-12-01

Full Text Available Le rôle des jardins dans le paysage anglais tient tout autant à ce qui se passe dans les esprits qu'aux réalités concrètes. L'apogée dans la création des jardins et des parcs influant sur le paysage campagnard a lieu au 18e siècle. Les créateurs d'alors visent à construire un paysage idéal; les périodes suivantes proposeront aussi les leurs.

Le patrimoine et ses outils de gestion

CERN Document Server

Garcin, J

2001-01-01

Les principale taches de gestion du Patrimoine immobilier du CERN sont la saisie des données, leur mise à jour, l'archivage et la mise à disposition des informations. Les outils de gestion actuels : Le Système de Gestion de Base de Données Relationnelles alphanumérique ORACLE permet de gérer toutes les informations du Patrimoine, sur le réseau du CERN. Le logiciel de dessin Graphique MICROSTATION (Bentley) a été installé dans la division ST depuis fin 1991. Les plans de situation des sites, des bâtiments et locaux, des espaces confinés ont été réalisés avec ce logiciel. Les outils de demain : La mise en place du SIG (Système d'Information Graphique) STAR a été réalisée en 1993. Le transfert des plans de locaux de MICROSTATION vers STAR est en cours depuis une année environ. Le dessin de la cartographie des réseaux de canalisations Eaux Usées et Eaux Pluviales est en cours de réalisation. Le Web est l'outil de consultation de l'information par les utilisateurs.

Le monde quantique

CERN Document Server

Aspect, A; Bensaude-Vincent, B; Castiel, A; Chevalley, C; Darrigol, O; Deligeorges, S; D'Espagnat, B; Laloë, F; Lévy-Leblond, J-M; Messiah, A; Paty, M; Vuillemin, J; Wheaton, B R

1984-01-01

Le monde quantique La physique quantique, après trois quarts de siècle, n'en finit pas d'être moderne. Elle est présente quotidiennement dans les laboratoires où les physiciens étudient atomes, noyaux et particules. Elle est entrée dans l'industrie où lasers, transistors et supraconducteurs lui doivent d'exister. Et elle continue à alimenter le débat philosophique sur la nature de la réalité dont elle montre la non-séparabilité fondamentale. Ses concepts de base, son développement, ses applications, ses controverses sont ici présentés par une pléiade de physiciens, d'historiens et de philosophes.

Le Pétrole et les dispersants dans les mers baignant le littoral canadien: évaluation des recherches et recommandations

National Research Council Canada - National Science Library

Sprague, John B; Vandermeulen, J. H; Wells, P. G; Birchard, E. C

1982-01-01

...; les methodes d'analyse; les effets du petrole, des dispersants et du petrole disperse chimiquement sur le phytoplancton, les macrophytes, le zooplancton, les poissons, les organismes et animaux benthiques et intertidaux, les oiseaux, les mammiferes marins, les communautes et les ecosystemes. Il comporte certaines recommandations en vue de recherches futures indispensables et donne des conseils sur la facon de minimiser les effets de deversements de petrole dans le milieu marin canadien.

Le CRDI dans les Philippines

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

Le CRDI appuie la recherche dans les. Philippines depuis 1972. Le travail qu'y ont accompli des universités et des instituts de recherche vigoureux et la participation active de la société civile ont entraîné d'importantes améliorations dans les domaines de l'agriculture, du suivi de la pauvreté et de la gestion des forêts.

Un oiseau "sabote" le CERN

CERN Multimedia

Colson, Sébastien

2009-01-01

Un oiseau, un simple oiseau, est parvenu à bloquer à lui tout seul l'accélérateur à particules à 3,7 milliards d'euros. UNe histoire quasiment bulresque qui a toutefois impacté le fonctionnement de la machine durant près de cinq jours, puisque c'est le système de refroidissement qui a été affecté. (1 page)

La nouvelle bourgeoisie islamique. Le modèle turc, de Dilek Yankaya

OpenAIRE

Lelandais, Gülçin Erdi

2016-01-01

De nombreux travaux sur la Turquie contemporaine ont été réalisés ces dernières années en France. La plus grande partie d’entre eux se focalise sur le champ politique et ses évolutions, les minorités ethniques — notamment les Kurdes –, et sur des mobilisations sociales, politiques et environnementales comme la mobilisation autour du parc Gezi. Le livre de Dilek Yankaya ouvre un nouveau champ d’analyse avec sa recherche, pionnière en son genre en France, qui étudie l’émergence d’une nouvelle é...

Le CERN et les Institutions

CERN Document Server

Barbalat, Oscar

1996-01-01

Une première partie de l'exposéŽ sera consacrée àˆ une brève description des principaux organes de l'Union EuropéŽennne: Conseil, Parlement et Commission ainsi que la structure de la Commission. On passera ensuite en revue le Programme-Cadre de Recherche et DéŽveloppement Technologique et les principaux programmes spéŽcifiques auxquels participe le CERN (ESPRIT, ACTS, TMR) On situera ensuite les autres organisations et initiatives scientifiques européŽennes (ESA, ESO, ESRF, JET, ISTC, EUREKA, ...) pour terminer par une brève revue des relations entre le CERN avec ces difféŽrentes institutions en déŽveloppant plus particulièrement celles avec la Commission.

Le nom Škerlj dans le cadre des noms Slovenes actuels

Directory of Open Access Journals (Sweden)

Franc Jakopin

1975-11-01

Full Text Available L'auteur du présent article place le nom Škerlj dans le cadre des noms slovènes actuels qui ont la même constitution phonetique, en éliminant les noms qui, par leur répartition géographique, leurs fréquences et caractéristiques formales, n'entrent pas dans ce cadre. A l'origine du nom Škerlj (et de ses variantes entrent l'appelatif skril (Schiefer et la base d'une onomatopée populaire škrlj (alauda. Par l'énorme force de créer les noms propres de cette derniere nommée, on chercherait l'origine du nom Škerlj surtout dans celle-ci.

Redresser les torts pour préparer un avenir meilleur : Le rôle des ...

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

1 févr. 2011 ... Des recherches préliminaires ont déjà été amorcées pour faire la lumière sur ces questions. (De fait, certaines des recherches les plus prometteuses sont nées de la collaboration entre le CRDI et le Centre international pour la justice transitionnelle.) Mais les obstacles qui empêchent de bien comprendre ...

Structure-based network analysis of activation mechanisms in the ErbB family of receptor tyrosine kinases: the regulatory spine residues are global mediators of structural stability and allosteric interactions.

Directory of Open Access Journals (Sweden)

Kevin A James

Full Text Available The ErbB protein tyrosine kinases are among the most important cell signaling families and mutation-induced modulation of their activity is associated with diverse functions in biological networks and human disease. We have combined molecular dynamics simulations of the ErbB kinases with the protein structure network modeling to characterize the reorganization of the residue interaction networks during conformational equilibrium changes in the normal and oncogenic forms. Structural stability and network analyses have identified local communities integrated around high centrality sites that correspond to the regulatory spine residues. This analysis has provided a quantitative insight to the mechanism of mutation-induced "superacceptor" activity in oncogenic EGFR dimers. We have found that kinase activation may be determined by allosteric interactions between modules of structurally stable residues that synchronize the dynamics in the nucleotide binding site and the αC-helix with the collective motions of the integrating αF-helix and the substrate binding site. The results of this study have pointed to a central role of the conserved His-Arg-Asp (HRD motif in the catalytic loop and the Asp-Phe-Gly (DFG motif as key mediators of structural stability and allosteric communications in the ErbB kinases. We have determined that residues that are indispensable for kinase regulation and catalysis often corresponded to the high centrality nodes within the protein structure network and could be distinguished by their unique network signatures. The optimal communication pathways are also controlled by these nodes and may ensure efficient allosteric signaling in the functional kinase state. Structure-based network analysis has quantified subtle effects of ATP binding on conformational dynamics and stability of the EGFR structures. Consistent with the NMR studies, we have found that nucleotide-induced modulation of the residue interaction networks is not

Gestion communautaire des ressources naturelles dans le Parc ...

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

En 2002, le Mozambique, l'Afrique du Sud et le Zimbabwe ont signé un accord établissant le Parc transfrontalier du Grand Limpopo (Greater Limpopo Trans Frontier Conservation Area), qui relie entre eux des parcs nationaux des trois pays et un ensemble de terres relevant pour la plupart de régimes fonciers communaux.

Addendum waarde commerciële radiovergunningen

NARCIS (Netherlands)

Poort, J.; Kerste, M.; Akker, I.; Prins, J.

2011-01-01

Op 18 mei 2010 stuurde de Minister van Economische Zaken het SEO-rapport Waarde commerciële radiovergunningen naar de Tweede Kamer. Dat rapport doet verslag van een onderzoek naar de waarde van de commerciële radiovergunningen. Het vormde de grondslag voor het financieel instrument in de

L’interface Habitat / Habitant : quand le lieu de vie est porteur de maladie - Le cas du radon en PACA

Directory of Open Access Journals (Sweden)

Cissé E.

2012-10-01

Full Text Available Les préoccupations sont croissantes pour étudier les liens entre des conditions environnementales spécifiques et la fréquence de certaines pathologies. Nous proposons d’analyser ici le lien présupposé entre une exposition au radon et le cancer du poumon. Le radon, est un gaz radioactif d’origine naturelle (issu de la désintégration naturelle de l’uranium présent dans la croûte terrestre et plus particulièrement dans certaines formations géologiques. A partir du sol et de l’eau, le radon se diffuse dans l’air (exhalation et se trouve, par effet de confinement, à des concentrations plus élevées à l’intérieur des bâtiments qu’à l’extérieur. Les descendants solides du radon sont alors inhalés avec l’air respiré et se déposent dans le poumon. Il est établi par diverses études scientifiques que le radon a un impact non négligeable sur certains cancers, notamment du poumon (augmentation de 16 % du risque de cancer du poumon par tranche de 100 Bq/m3, et des cancers digestifs via la consommation d’eau qui s’est chargée en radon au contact du socle. Le nombre annuel de décès par cancer du poumon attribuable à l’exposition domestique au radon en France métropolitaine varie entre 1 200 à 3 575 en fonction des relations exposition-réponse utilisées. Plusieurs régions en France se caractérisent par une problématique radon reconnue et étudiée depuis longtemps (Bretagne, Massif central, Corse. Or, si le radon ne recouvre pas l’ensemble de la région PACA, certaines zones géographiques sont particulièrement concernées et méritent d’être étudiées : le Massif des Maures dans le Var, du Mercantour dans les Alpes-Maritimes et du Briançonnais dans les Hautes-Alpes. La région PACA est une des régions de France et d’Europe les plus touchées par la pollution atmosphérique principalement due à l’augmentation du trafic routier et des contributions de régions industrialisées telles que

Apprendre ensemble en classe via des jeux vidéo populaires : le modèle du LAN pédagogique

Directory of Open Access Journals (Sweden)

Samuelle Ducrocq-Henry

2011-05-01

Full Text Available La thèse intitulée « Les tribus ludiques» expose le modèle du LAN pédagogique (LP découlant d’une étude des compétitions de jeu vidéo en réseau local (LAN parties. Incarnant un rite de passage quasi tribal chez les 12-25 ans, les LAN semblent favoriser socialisation et apprentissage. Un LP permet aux enseignants d’initier des expériences réseautiques similaires et formatrices en classe, tenues simultanément dans les mondes réels et virtuels, en détournant le scénario de jeux vidéo multijoueurs populaires, pour en faire des simulateurs propices à l’enseignement de disciplines diverses. Sa procédure simple et abordable révèle le potentiel du Serious Gaming en éducation.

Promouvoir le développement durable dans le commerce mondial et les négociations multilatérales

Directory of Open Access Journals (Sweden)

Christophe Bellmann

2011-05-01

Full Text Available Les exportations et les importations mondiales reprennent rapidement du volume après le fort déclin accusé par le commerce de marchandises en 2008-2009, comme l’indiquent les performances du commerce mondial des premier et deuxième trimestres de 2010. En dépit de cette reprise impressionnante, les préoccupations des pays de l’OCDE relatives à l’emploi, à la compétitivité et à la politique chinoise des taux de change ont engendré un climat politique défavorable à la poursuite de la libéralisation dans le cadre du Cycle de Doha. Il est intéressant de noter que les pays en développement qui hésitaient à s’engager dans un nouveau cycle de négociations en 2001 se situent maintenant à l’avant-garde de ceux qui souhaitent parvenir rapidement à une conclusion des pourparlers, bien que le consensus sur l’ambitieux « paquet du développement » envisagé initialement à Doha reste hors d’atteinte. Par ailleurs, le commerce a fait l’objet d’une attention et d’un examen sans précédents dans le cadre des débats sur les changements climatiques. Dans le contexte créé par la crise de la coopération multilatérale, la communauté internationale a un urgent besoin de générer de nouveaux types d’arrangements et de trouver des réponses innovantes aux impératifs du développement et de la transition mondiale vers une économie à faible intensité de carbone.

Le piano touchant/touché: l'instrument du contretemps chez Gide, le cas du Journal et des Notes sur Chopin

OpenAIRE

Zorica Vukušić, Maja

2011-01-01

André Gide, romancier, essayiste, critique et traducteur, a été le diariste dont le journal (écrit de 1887 jusqu`à 1949) est imbibé de musique. Gide a aussi été pianiste – amateur (dans le sens barthésien du terme), tout comme Nietzsche, Sartre ou Barthes. Leur proximité nous est donnée dans une sorte de polémique imaginée qui dépasse le discours. Sans doute Adorno et Jankélévitch ont été meilleurs pianistes et meilleurs philosophes de la musique, mais Gide s`est éloigné de la ...

Rôle du couvre-sol dans le développement du chancre bactérien dans les vergers d’abricotiers

OpenAIRE

Peyre, Manon

2017-01-01

Le genre Pseudomonas, inclut plusieurs espèces de bactéries phytopathogènes, comme les Pseudomonas syringae qui provoque la bactériose, maladie conduisant généralement à la mort des arbres fruitiers. A l’heure actuelle, les moyens de lutte contre P. syringae sont très réduits ou inexistants. Ainsi, des méthodes alternatives ou le rôle de certains éléments comme la présence de réservoirs de la bactérie sont en cours d’étude. Partant de l’hypothèse que le couvre-sol pourrait être une source...

Le modèle périurbain à l’épreuve de la catastrophe

Directory of Open Access Journals (Sweden)

Julien Langumier

2007-05-01

Full Text Available Le modèle périurbain pavillonnaire est questionné à partir d'une démarche ethnographique conduite sur un village du Narbonnais touché par des inondations catastrophiques. L'histoire de ce mode d'urbanisation montre les liens forts qui existent avec les dynamiques territoriales, en l'occurrence la crise viticole des années soixante-dix. L'inondation de 1999 perturbe ensuite les pratiques domestiques et conduit les sinistrés à redéfinir leur mode d'habiter en délaissant le bonheur pavillonnaire au profit de la quête de sécurité. Les discours des gestionnaires connaissent enfin un renversement depuis le développement urbain des campagnes des années quatre-vingt à l'imposition de la "culture du risque" dans ces quartiers à l'avenir incertain. L'approche ethnologique suit les multiples recompositions du modèle périurbain à travers l'histoire d'un territoire, les pratiques des habitants et les discours des gestionnaires.Suburbanisation is about to represent an unsustainable model of urban development for consummating space, energy and equipments. In this context, the tragic floods which affected Cuxac d’Aude village (Aude, France in 1999 can be explained by hazardous choices of planning suburban neighbourhood in risky places. The ethnographical research proposes an other approach which focuses on the bonds with the territory and the residential practices. For the deep wine crises of the 70’s and 80’s in Languedoc, the urbanization of old vineyards participates to the modernization of rural areas. After the floods, the inhabitants define new domestic practices in damaged houses. The suburban villa is no more the modern symbol of happiness but is the place of fear, stress and risk culture.

Centre de recherches pour le développement international ...

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

André Lavoie

Definitions. 5. Rôles et ... a) Le Centre de recherches pour le développement international (CRDI) est une société d'État canadienne à .... conduite éthique dans le cadre de ces activités afin que la confiance du public dans .... a) Les gouverneurs en déplacement pour le compte du CRDI ont droit à une indemnité de repas et ...

Le littoral face aux changements climatiques

OpenAIRE

Mulot, Vanessa; Vigneron, Anne-Laure; Lambert-Hadid, Marie-Laure

2011-01-01

Le changement climatique et l’anthropisation du littoral accentuent le risque de submersion marine sur l’ensemble des côtes. Malgré l’élévation en cours du niveau des mers, l’attractivité du littoral ne décroît pas malgré la connaissance du risque. Ce risque aggravera dans les années à venir les enjeux liés à la submersion marine, parmi lesquels le danger pour les vies humaines, comme l’a malheureusement illustré l’actualité (Xynhia), mais aussi la question de la propriété des biens et des te...

Vivre avec ou par le risque à l’île de Sein ?

Directory of Open Access Journals (Sweden)

Annaig Oiry

2012-02-01

Full Text Available L’île de Sein, située au large des côtes finistériennes, fait figure de « territoire du risque » par excellence : cette île basse est confrontée à de fréquentes et violentes tempêtes, la population vit « avec le risque » de submersion depuis des générations tout en voyant la probabilité des aléas catastrophiques augmenter en raison de la carence en aménagement et des conséquences probables du réchauffement climatique. L’image du risque, notamment les photographies de tempête, sert de support à la diffusion d’un sentiment anxiogène justifiant des actions de gestion du risque, mais entretient aussi un sentiment de fascination à l’égard des épisodes tempétueux. Cependant, les îliens portent un regard bien plus critique sur le spectaculaire véhiculé par de telles représentations. Le présent article se penche sur ces rapports entre représentations sociales du risque et iconographie du risque.This article stresses on relationships between hazard’s social representations and iconographies. As an illustration, Sein Island (located near by the Brittany coast, in Finistère. This island is considered as a symbol of natural hazard territory: indeed this low island has been confronted for decades to face significant flood hazard that is nowadays strengthened by the consequences of global warming and a lack of infrastructures. Pictures of flood hazards, and more particularly pictures of storms, are used in order to spread around the fear of natural disasters. This fear justifies the management policies implemented on the island. However islanders criticize pictures which are too spectacular and too distorted. Those gaps between hazard’s representations and iconographies are the main subjects of this article.

Initiative Think tank | CRDI - Centre de recherches pour le ...

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

L'ITT est le fruit d'un partenariat regroupant cinq bailleurs de fonds. Lancée en 2008, l'ITT est administrée par le Centre de Recherches pour le Développement International (CRDI), un organisme canadien.

Reformulation à l’oral et dans le forum Web

Directory of Open Access Journals (Sweden)

Eshkol-Taravella Iris

2016-01-01

Full Text Available Le cadre du travail réalisé entre dans le domaine de la linguistique de corpus et du Traitement Automatique des Langues (TAL. Les recherches sont fondées sur trois corpus : deux corpus oraux (ESLO1 et ESLO2 et un corpus composé de discussions collectées sur un forum de Doctissimo. Le travail vise à détecter, analyser et comparer la reformulation introduite par trois marqueurs (c’est-à-dire, je veux dire et disons dans le discours oral et le corpus écrit dialogique du Web. L’objectif est d’étudier la raison pour laquelle le locuteur décide de modifier un segment par un autre et de repérer un lien formel entre les deux segments reformulés aux différents niveaux linguistiques (morphologique, lexical, syntaxique, etc..

Kuidas kirjutatakse ajalugu? / Jacques Le Goff ; interv. Marek Tamm

Index Scriptorium Estoniae

Le Goff, Jacques

2007-01-01

Prantsuse ajaloolase ja ajakirja Annales ühe peatoimetaja J. Le Goff'i teostest. Varem. ilm.: Ajalugu, antropoloogia ja imaginaarsus : intervjuu Jaques Le Goffiga // Le Goff, Jacques. Raha või elu : majandus ja religioon keskajal. - Tallinn, 2001. - Lk. 108-126

Un’architettura per e con le persone

Directory of Open Access Journals (Sweden)

Alessandro Rigolon

2011-06-01

Full Text Available L’articolo propone un approccio umanistico al progetto architettonico, ponendo le persone al centro del processo di concezione. Comprendere il modo in cui lo spazio influenza il comportamento, le emozioni e le attività delle persone dovrebbe essere il punto di partenza del progetto. Ciò implica una riflessione sui mezzi con i quali lo spazio trasmette significati connotativi e denotativi. Le tecniche per raccogliere informazioni dagli utenti e per includere tali informazioni nel progetto sono state analizzate per evidenziare i vantaggi e i problemi del mettere in pratica tale approccio umanistico. La discussione finale è focalizzata sulla possibile perdita di autonomia del progettista, sulla tempistica dell’introduzione dei dati derivati dagli utenti e sulle conseguenze dell’inclusione di tali dati nelle normali pratiche progettuali.

Le style modal de la science-fiction

Directory of Open Access Journals (Sweden)

Emmanuel Boisset

2013-04-01

Full Text Available La faiblesse de style dont souffrirait la science-fiction est en fait le signe que la science y est davantage discours du possible que description du réel. Un « style modal » va suspendre la valeur de vérité, et le style de la possibilité va décontextualiser les métaphores disponibles. En science-fiction, le processus métaphorique génère et structure la diégèse. Un exemple chez Iain M. Banks montre un dialogue quasi incompréhensible mettre à l’épreuve la signification comme possibilité. Les métaphores figées sont revitalisées par la décontextualisation de la fiction, dont le texte peut exploiter l’impertinence.

Rôle des coopératives dans le fonctionnement du bassin de collecte laitier du Tadla, Maroc

OpenAIRE

Le Gal , P.-Y.; Oudin , E.; Kuper , M.; Moulin , C.-H.; Sraïri , T.

2007-01-01

International audience; Le bassin de collecte laitier situé sur le périmètre du Tadla se structure autour d'une usine de transformation industrielle approvisionnée par une myriade de petits éleveurs. Cette atomisation de l'offre a rendu nécessaire la mise en place de coopératives de collecte chargées d'agréger l'offre et d'assurer la chaîne du froid au plus près des producteurs. De fait, ces coopératives jouent un rôle central d'intermédiaire dans la chaîne d'approvisionnement allant de l'eau...

Le « souverain remède » :esquisse d’une érotique libertine dans Le Gascon extravagant

Directory of Open Access Journals (Sweden)

Michèle Rosellini

2007-06-01

Full Text Available Le Gascon extravagant peut être défini comme roman libertin dans la mesure où il raconte l’éducation érotique de son héros. Ce récit d’éducation suit un mouvement négatif qui, de déception en déconvenue, conduit le personnage à renoncer à toute idéalisation de l’amour et à se borner à la recherche du plaisir. Il retrouve ainsi par son expérience la leçon épicurienne de Lucrèce qui invite à distinguer le pur désir, qui promet le plaisir, de l’amour, qui le plus souvent fait souffrir. Transposée dans le cadre idéologique du roman comique, de tradition gauloise, cette éthique paraît plus cynique que libératrice. Mais le roman n’est pas simple illustration de la philosophie. Par son dispositif narratif et son langage propre, il permet de mettre en débat la morale misogyne du héros-narrateur et de proposer, par-delà toute doctrine, l’exploration d’une expérience du corps encore inédite. C’est par là que le roman comique réalise son ambition, véritablement libertine, d’émanciper le lecteur des préjugés sexuels de son temps et de son milieu.Le Gascon extravagant can be defined as a libertine novel in the measure in which it narrates the erotic education of its hero.  This account of his education follows a negative movement, which, from deception to disappointment, leads the character to renounce all idealized images of love and to confine himself to the search for pleasure.  In so doing, he comes to discover Lucrèce's Epicurean lesson, which invites to distinguish pure desire, wich promises pleasure, and love, wich often brings suffering. Transposed in the ideological framework of the comic novel, of Gauloise tradition, this ethic appears to be more cynical than liberating.  The novel, however, is not a mere illustration of philosophy.  By means of its narrative structure and its own language, it is able to question the misogynous morale of the narrator-hero and to propose, beyond any

Facteurs de risque de l'infection par le VIH dans le district de santé de Meyomessala au Cameroun

Science.gov (United States)

Mbopi-Keou, Francois-Xavier; Nguefack-Tsague, Georges; Kalla, Ginette Claude Mireille; Abessolo, Stéphanie Abo'o; Angwafo, Fru; Muna, Walinjom

2014-01-01

Introduction L'objectif de ce travail était de déterminer les facteurs de risque de l'infection par le VIH dans le district de santé de Meyomessala (Région du Sud) au Cameroun. Méthodes Il s'agissait d'une étude transversale, descriptive et analytique qui s'est déroulée de Février à Mai 2011. Pour cette étude, nous avons obtenu une clairance éthique. Résultats L’échantillon était constitué de 315 participants dont 181 (57,46%) hommes et 134 (42,54%) femmes. L’âge moyen était de 24,5±8ans (extrême: 15-45ans). Quarante personnes (40) étaient séropositifs, soit une prévalence de l'infection par le VIH de 12,7%. Cette prévalence augmentait significativement (p = 0) avec le nombre de partenaires occasionnels au cours des douze derniers mois, allant de 2,7% chez ceux n'ayant eu aucun partenaire occasionnel à 21,25% chez ceux ayant plus de trois partenaires occasionnels (RC = 9,72; IC = 1,27-74,14; P = 0,03). le fait d’être âgé entre 20 et 24 ans (RC = 4,88; IC = 1,74-13,67; p = 0), avoir plus de trois partenaires sexuels au cours des douze derniers mois (RC = 9,72; IC = 1,27-74,14; p = 0,03), avoir les rapports sexuels avec les prostitués (RC = 2,86; IC = 1,42-5,76; p = 0), avoir eu le chlamydia (RC = 3,00; IC = 1,07-8,39; p = 0,04), avoir eu la syphilis (RC = 3,35; IC = 1,57-7,14; p = 0), avoir des avantages sociaux lors du premier rapport sexuel (RC = 2,57; IC = 1,03-6,43; p = 0,04) constituaient des potentiels facteurs de risque du VIH. Conclusion Il apparait urgent d'intensifier les campagnes de sensibilisation au risque d'infection par le VIH et les maladies sexuellement transmissibles dans le district de santé de Meyomessala PMID:25419299

Contester le mariage forcé : mettre en place la ligne de défense et le ...

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

Le mariage forcé viole les principes de liberté personnelle et d'autonomie individuelle. Il est considéré comme une violation des droits de la personne aux termes du droit international en matière de droits de la personne. Ce projet produira des données probantes qui aideront à combattre le mariage forcé en Inde ...

Le contrôle de la reproduction chez les poissons.

Directory of Open Access Journals (Sweden)

CHEVASSUS B.

1979-07-01

Full Text Available L'utilisation de populations monosexes peut permettre d'accroître la rentabilité économique, lorsque la reproduction est trop rapide (aquaculture extensive dans les pays tropicaux ou dans le cas d'espèces où l'un des sexes est plus avantageux (meilleure vitesse de croissance ou maturation plus tardive. Nous avons analysé dans ce papier quatre méthodes permettant la production de populations monosexes. Si l'inversion sexuelle par traitement hormonal ou (a gynogenèse induite (dans le cas d'une homogamétie femelle ne semblent pas directement exploitables, on peut attendre du sexage génétique qui combine ces deux méthodes, des résultats prometteurs. L'hybridation interspécifique peut également conduire à une descendance monosexe dans des cas particuliers.

A phase I study with neratinib (HKI-272), an irreversible pan ErbB receptor tyrosine kinase inhibitor, in patients with solid tumors.

Science.gov (United States)

Wong, Kwok-K; Fracasso, Paula M; Bukowski, Ronald M; Lynch, Thomas J; Munster, Pamela N; Shapiro, Geoffrey I; Jänne, Pasi A; Eder, Joseph P; Naughton, Michael J; Ellis, Matthew J; Jones, Suzanne F; Mekhail, Tarek; Zacharchuk, Charles; Vermette, Jennifer; Abbas, Richat; Quinn, Susan; Powell, Christine; Burris, Howard A

2009-04-01

The dose-limiting toxicities, maximum tolerated dose, pharmacokinetic profile, and preliminary antitumor activity of neratinib (HKI-272), an irreversible pan ErbB inhibitor, were determined in patients with advanced solid tumors. Neratinib was administered orally as a single dose, followed by a 1-week observation period, and then once daily continuously. Planned dose escalation was 40, 80, 120, 180, 240, 320, 400, and 500 mg. For pharmacokinetic analysis, timed blood samples were collected after administration of the single dose and after the first 14 days of continuous daily administration. Dose-limiting toxicity was grade 3 diarrhea, which occurred in one patient treated with 180 mg and in four patients treated with 400 mg neratinib; hence, the maximum tolerated dose was determined to be 320 mg. Other common neratinib-related toxicities included nausea, vomiting, fatigue, and anorexia. Exposure to neratinib was dose dependent, and the pharmacokinetic profile of neratinib supports a once-a-day dosing regimen. Partial response was observed for 8 (32%) of the 25 evaluable patients with breast cancer. Stable disease >or=24 weeks was observed in one evaluable breast cancer patient and 6 (43%) of the 14 evaluable non-small cell lung cancer patients. The maximum tolerated dose of once-daily oral neratinib is 320 mg. The most common neratinib-related toxicity was diarrhea. Antitumor activity was observed in patients with breast cancer who had previous treatment with trastuzumab, anthracyclines, and taxanes, and tumors with a baseline ErbB-2 immunohistochemical staining intensity of 2+ or 3+. The antitumor activity, tolerable toxicity profile, and pharmacokinetic properties of neratinib warrant its further evaluation.

Le Kongo de Sony Labou Tansi

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Céline Gahungu

2015-02-01

Full Text Available Les textes inédits de Sony Labou Tansi proposent une réflexion sur l’histoire, et plus singulièrement sur celle du Kongo. Le souvenir du prestigieux royaume apparaît dès les premiers manuscrits, composés au début des années 1970. Loin d’être circonscrit aux écrits de jeunesse, le Kongo surgit sous de multiples formes dans le dédale des textes rédigés au cours des années suivantes. Cette fascination pousse l’écrivain dans une dynamique de recherche esthétique : comment évoquer cet illo tempore mythique sans sacrifier à une historicité convenue ? Comment inventer une écriture en mesure de rendre compte du fabuleux royaume ?L’analyse littéraire ne peut cependant faire fi du contexte politique dans lequel Sony Labou Tansi s’inscrit. Outre sa dimension historique et toponymique, Kongo est un ethnonyme dont l’auteur s’est réclamé. Celui-ci a revendiqué à de nombreuses reprises son appartenance à une identité kongo au point de s’être engagé, à la fin des années 1980, dans les rangs du MCDDI1. Ce discours identitaire et l’adhésion à un parti ethnique ont troublé l’image d’un auteur volontiers perçu comme un démocrate véritable. Est-il possible d’articuler le Kongo littéraire et le Kongo politique ? Le Kongo, dont l’ombre portée apparaît dans les manuscrits littéraires mais également dans les articles et les déclarations politiques, pourrait-il nous aider à saisir les enjeux de l’écriture protéiforme de Sony Labou Tansi ?

Fonds d'innovation en vaccins pour le bétail : renforcement des ...

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

Fonds d'innovation en vaccins pour le bétail : renforcement des capacités de recherche. Ce projet donne l'autorisation d'appuyer le renforcement des capacités afin de mettre en place le Fonds d'innovation en matière de vaccins pour le bétail et de le gérer. Le Fonds vise à financer le développement de vaccins de qualité ...

Searching the animal psyche with Charles Le Brun.

Science.gov (United States)

Cohen, Sarah R

2010-07-01

Around 1670 the French court painter and Academician Charles Le Brun produced a series of drawings featuring naturalistic animal heads, as well as imaginary heads in which he refashioned various nonhuman animal species to make humanoid physiognomies. What were the purpose and significance of these unusual works? I argue that they show Le Brun's interest in what we today would call animal psychology: focusing upon the sensory organs and their connections with the animal's brain, Le Brun studied his animals as conscious protagonists of the natural realm. One source that may have served him in this project was Marin Cureau de La Chambre's De la Connoissance des bestes of 1645, in which the physician argued that animals possess a conscious soul grounded in the senses. However, Le Brun's animal-humans have no clear place in the artist's taxonomy--nor, indeed, in any seventeenth-century understandings of species. It is rather John Locke, at his most skeptical, who offers the best parallel in the realm of natural philosophy to Le Brun's unsettling animal-humans. Probably without meaning to, Le Brun demonstrated through his eerie, boundary-crossing creatures the limits of visual classification.

En un lugar del aula… De lo que le sucedió a don Quijote en una clase de E/LE

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Luz Celestina Souto

2017-11-01

Full Text Available Resumen: El presente trabajo tiene como objetivo mostrar una vía para la lectura de El ingenioso hidalgo don Quijote de la Mancha en el aula de E/LE. La propuesta se realizará a través de una selección de recursos y actividades sobre el clásico de Cervantes. Las preguntas desde las cuales se parte para el planteamiento son: ¿Qué es un clásico? ¿Por qué leer a Cervantes en la clase de E/LE? ¿Cómo leerlo? ¿Qué ventajas tiene El Quijote en el siglo xxi para quienes tienen el español como segunda lengua? Palabras Clave: Siglo de Oro, Quijote, clase de E/LE, literatura   Abstract: The present work aims to show a way to read El ingenioso hidalgo don Quijote de la Mancha in the E/LE class. The proposal is made through a selection of resources and activities about Cervantes. The questions we ask are: what is a classic? Why read Cervantes in E/LE class? How to read it? What are advantages of  El Quijote in the 21st century for those who have Spanish as a second language? Keywords: Spanish Golden Age, Quixote, E/LE class, literature

Le Chatelier's principle in replicator dynamics

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Allahverdyan, Armen E.; Galstyan, Aram

2011-10-01

The Le Chatelier principle states that physical equilibria are not only stable, but they also resist external perturbations via short-time negative-feedback mechanisms: a perturbation induces processes tending to diminish its results. The principle has deep roots, e.g., in thermodynamics it is closely related to the second law and the positivity of the entropy production. Here we study the applicability of the Le Chatelier principle to evolutionary game theory, i.e., to perturbations of a Nash equilibrium within the replicator dynamics. We show that the principle can be reformulated as a majorization relation. This defines a stability notion that generalizes the concept of evolutionary stability. We determine criteria for a Nash equilibrium to satisfy the Le Chatelier principle and relate them to mutualistic interactions (game-theoretical anticoordination) showing in which sense mutualistic replicators can be more stable than (say) competing ones. There are globally stable Nash equilibria, where the Le Chatelier principle is violated even locally: in contrast to the thermodynamic equilibrium a Nash equilibrium can amplify small perturbations, though both types of equilibria satisfy the detailed balance condition.

Festivals de cinéma dans le monde arabe

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Jean-Michel Frodon

2013-12-01

Full Text Available Alors que les deux grands festivals « historiques » du monde arabe, Carthage (JCC et Le Caire, sont entrés en décadence, on assiste depuis le début des années 2000 à une véritable explosion du phénomène festivalier dans le monde arabe. Le pays le plus en pointe est le Maroc, quoique de manière contrastée, avec une manifestation de prestige à Marrakech, et une nuée de petites manifestations. Dans les émirats du Golfe, la multiplication des festivals traduit une stratégie de communication plutôt qu’une volonté de développement culturel. Cette stratégie est fragilisée par la concurrence que se livrent les différents acteurs. Dans les autres pays arabes, on trouve une grande variété de situations sous le signe de la dispersion. Pourtant, l’accumulation de festivals (une centaine dans la région finit par avoir des effets d’ensemble, au-delà des buts, moyens et limites de chacun d’eux. Le phénomène festivalier, bien qu’inscrit dans des agendas locaux ou nationaux, génère de manière plus vaste des réseaux générationnels, financiers, de procédures d’expertise, de processus d’interrelation, géographiques mais aussi entre le cinéma et les autres arts ou médias.

Le mal et ses complots imaginaires

OpenAIRE

Frankfurter, David

2012-01-01

Les récits d’abus rituels sataniques que les médias ont largement diffusés, aux États-Unis et au Royaume-Uni, entre le début des années 1980 et la fin des années 1990, soutenaient le parallèle avec les allégations avancées, durant l’Antiquité et au début des Temps modernes, contre les chrétiens, les hérétiques, les juifs ou les sorcières. Quelle est la nature de ces parallèles ? Cet article examine plusieurs types de modèles convoqués lors de diverses occurrences historiques des peurs panique...

Les nouveaux mécanismes du contrôle organisationnel

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Rosimeri Carvalho da Silva

Full Text Available Dans cet essai on discute les mécanismes de contrôle mis en évidence par l'adoption de nouvelles technologies de gestion qui ont proporcionné une restructuration productive. La relevance de cette discussion est dans la compréhension que l'adoption de ces nouvelles technologies impliquent des alterations dans le système de contrôle que, même si elles ne remplacent pas complètement les modes de contrôle utilisés avant, mettent l'accent sur un mode de contrôle plus subtil que privilegie des mécanismes qu'influencient le partage d'une vision de monde.

Publications | Page 160 | CRDI - Centre de recherches pour le ...

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

africain. Il y a deux ans, le Centre de recherches pour le développement ... African Youth on the Information Highway : Participation and Leadership in Community Development. Tout comme elle l'a fait dans le Nord industrialisé, la révolution de ...