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Sample records for le erbe medicinali

  1. Falsificazione di medicinali, criminalità organizzata e cooperazione internazionale

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    Anna G. Micara

    2016-07-01

    Full Text Available La contraffazione dei medicinali rappresenta una minaccia per tutti i Paesi della Comunità internazionale ed è strettamente legata alla criminalità organizzata. Il carattere transnazionale di tale fenomeno rende evidente l’importanza della cooperazione internazionale in materia che, tuttavia, non è ancora adeguatamente sviluppata. Nonostante i progressi relativi alla nozione di medicinale falsificato, non vi è ancora una definizione comune negli strumenti internazionali analizzati. Inoltre, la Convenzione MEDICRIME, appena entrata in vigore, rappresenta un notevole passo avanti per il rafforzamento del quadro sanzionatorio a livello internazionale ma non vi sono adeguatamente disciplinati gli aspetti legati alla criminalità organizzata. Vengono perciò in rilievo l’applicabilità della Convenzione UNCTOC alla falsificazione dei medicinali, il modello di legislazione UNODC sulle medicine fraudolente e le ipotesi di elaborazione di uno strumento internazionale di più ampio respiro.   Counterfeiting of medicines is a threat to the whole international community and is deeply related to organised crime. The transnational dimension of this multifaceted phenomenon makes necessary to develop international instruments to tackle it. However, and notwithstanding the advancements on the notion of falsified medicines, there is not a common definition in the international legal instruments analyzed. Furthermore, the MEDICRIME Convention, although representing a remarkable step forward concerning criminal sanctions, has been ratified by few States and does not adequately take into account aspects related to the organized crime involvement. In this regard, the applicability of the UN Convention against Transnational Organized Crime to the falsification of medicines and the draft model law of UNODC on fraudulent medicines become relevant. Finally, the proposals to elaborate a broader international instrument within the WHO or the UNODC do not seem

  2. Voelt de medicinale bloedzuiger Hirudo medicinalis zich wel zo lekker in Nederland (Hirudinea)?

    NARCIS (Netherlands)

    Felix, R.P.W.H.; Velde, van der G.

    2000-01-01

    Does the medicinal leech Hirudo medicinalis feel well in the Netherlands (Hirudinea)? This paper provides information on the medicinal leech Hirudo medicinalis Linnaeus, 1758 particularly in The Netherlands. Although this species was common in The Netherlands in the 18th century, nowadays it is very

  3. Voelt de medicinale bloedzuiger Hirudo medicinalis zich wel zo lekker in Nederland (Hirudinea)?

    OpenAIRE

    Felix, R.P.W.H.; Velde, van der, G.

    2000-01-01

    Does the medicinal leech Hirudo medicinalis feel well in the Netherlands (Hirudinea)? This paper provides information on the medicinal leech Hirudo medicinalis Linnaeus, 1758 particularly in The Netherlands. Although this species was common in The Netherlands in the 18th century, nowadays it is very rare. Most animals were found in waters on sandy soil (71%): dune pools (10%) and pleistocene sandy areas (61%), where it inhabits especially soft water moor and heathland pools. About 20% of the ...

  4. Naragh Suburb, Center of Iran; A Natural Habitat of Hirudo medicinalis

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    Dehghani R.1 PhD,

    2014-08-01

    Full Text Available Aims A very common species of leeches has been named as Hirudo medicinalis. Regarding to the application of leeches in medicine and their fast extinction, this study was performed in aquatic habitats of Kashan aimed to determine the distribution of leeches and to provide information about their regional and habitat characteristics. Materials & Methods This descriptive study was conducted during 2008 to 2010 in three periods and 90 samples from 30 sites were collected, totally. 30 lentic and lotic aquatic habitats located in different regions of Naragh were recognized and selected. Leeches were collected initially in 10% ethanol followed by washing and removing mucus and then maintained in 70% ethanol. The identification keys were used for recognizing the species of leeches. Findings According to the identification key of the leech species, 15 samples from the total samples of 30 locations were Hirudo medicinalis. Total Hirudo medicinalis samples were collected just from Naragh River. These species of leeches were relatively large with 7-10cm and their colors were olive green, brown and greenish brown with a red stripe on the sides. Conclusion Naragh River is one of the habitats of Hirudo medicinalis.

  5. 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.

  6. 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.

  7. 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 ...

  8. 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.

  9. 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

  10. 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.

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

    Science.gov (United States)

    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.

  12. 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.

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

    Science.gov (United States)

    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.

  14. Acute oral toxicity and anti-inflammatory activity of hydroalcoholic extract from Lampaya medicinalis Phil in rats.

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    Morales, Glauco; Paredes, Adrián; Olivares, Alberto; Bravo, Jaime

    2014-03-26

    Algesia and inflammation are related with several pathological conditions. It is known that many drugs available for the treatment of these problems cause unwanted side effects. This study was aimed at evaluating acute toxicity and anti-inflammatory activity of Lampaya medicinalis Phil. (Verbenaceae) widely used in the folk medicine of Northern Chile against rheumatism, arthritis and body joints pain. Oral administration of hydroalcoholic extract (HAE) at the highest dose of 3000 mg/ Kg body weight resulted in no mortalities or evidence of significant behavioral changes. Histological examination revealed normal architecture and no significant adverse effects were observed on the liver, kidney, heart, lung or ovaries and testicles. The results suggest that the oral administration of hydroalcoholic extract (HAE) from Lampaya medicinalis did not produce any toxic effect in rats. Hydroalcoholic extract (HAE) significantly inhibited the carrageenan-induced rat paw edema in dose - response relationship, at test doses of 37.5, 75, 150 and 300 mg/Kg body weight. Maximum inhibition (61.98 ± 2.69%) was noted at 300 mg/Kg after 2 h of drug treatment carrageenan induced paw edema, whereas indomethacin produced 47.90 ± 1.16% of inhibition. The inhibitory values of edema at 3 h postcarrageenan were 31.04 ± 0.75%, 40.51 ± 2.36%, 48.97 ± 1.14% and 56.87 ± 0.41% for 37.5, 75, 150, and 300 mg/kg of extract respectively. Indomethacin (10 mg/Kg) gave a percentage inhibition of 49.44 ± 1.44. HAE (300 and 150 mg/kg) induced an anti-inflammatory effect greater than (or comparable) with the effect of indomethacin from 2nd to 4th hours of the experiment. Our results reveal for first time that compounds contained in the hydroalcoholic extract of Lampaya medicinalis Phil exert anti-inflammatory effect and the oral administration is safe and non toxic up to dose level 3000 mg/kg body weight. The anti-inflammatory activity may be associated with the presence of flavonoids. These

  15. Acute oral toxicity and anti-inflammatory activity of hydroalcoholic extract from Lampaya medicinalis Phil in rats

    Directory of Open Access Journals (Sweden)

    Glauco Morales

    2014-01-01

    Full Text Available BACKGROUND: Algesia and inflammation are related with several pathological conditions. It is known that many drugs available for the treatment of these problems cause unwanted side effects. This study was aimed at evaluating acute toxicity and anti-inflammatory activity of Lampaya medicinalis Phil. (Verbenaceae widely used in the folk medicine of Northern Chile against rheumatism, arthritis and body joints pain. RESULTS: Oral administration of hydroalcoholic extract (HAE at the highest dose of 3000 mg/ Kg body weight resulted in no mortalities or evidence of significant behavioral changes. Histological examination revealed normal architecture and no significant adverse effects were observed on the liver, kidney, heart, lung or ovaries and testicles. The results suggest that the oral administration of hydroalcoholic extract (HAE from Lampaya medicinalis did not produce any toxic effect in rats. Hydroalcoholic extract (HAE significantly inhibited the carrageenan-induced rat paw edema in dose - response relationship, at test doses of 37.5, 75, 150 and 300 mg/Kg body weight. Maximum inhibition (61.98 ± 2.69% was noted at 300 mg/Kg after 2 h of drug treatment carrageenan induced paw edema, whereas indomethacin produced 47.90 ± 1.16% of inhibition. The inhibitory values of edema at 3 h postcarrageenan were 31.04±0.75%, 40.51 ± 2.36%, 48.97 ± 1.14% and 56.87 ± 0.41% for 37.5, 75, 150, and 300 mg/kg of extract respectively. Indomethacin (10 mg/Kg gave a percentage inhibition of 49.44 ± 1.44. HAE (300 and 150 mg/kg induced an anti-inflammatory effect greater than (or comparable with the effect of indomethacin from 2nd to 4th hours of the experiment. CONCLUSIONS: Our results reveal for first time that compounds contained in the hydroalcoholic extract ofLampaya medicinalis Phil exert anti-inflammatory effect and the oral administration is safe and non toxic up to dose level 3000 mg/kg body weight. The anti

  16. Rev-erbα and Rev-erbβ coordinately protect the circadian clock and normal metabolic function

    DEFF Research Database (Denmark)

    Bugge, Anne Skovsø; Feng, Dan; Everett, Logan J

    2012-01-01

    of binding sites across the genome, enriched near metabolic genes. Depletion of both Rev-erbs in liver synergistically derepresses several metabolic genes as well as genes that control the positive limb of the molecular clock. Moreover, deficiency of both Rev-erbs causes marked hepatic steatosis, in contrast......-autonomous clock as well as hepatic lipid metabolism. Mouse embryonic fibroblasts were rendered arrhythmic by depletion of both Rev-erbs. In mouse livers, Rev-erbβ mRNA and protein levels oscillate with a diurnal pattern similar to that of Rev-erbα, and both Rev-erbs are recruited to a remarkably similar set...

  17. Description and notes on natural history of a new species of Parosus Sharp, 1887 (Coleoptera, Staphylinidae, Oxytelinae) living in floral bracts of Columnea medicinalis L. (Gesneriaceae).

    Science.gov (United States)

    LÓpez-garcÍa, Margarita M; MarÍn-gÓmez, Oscar H

    2018-03-16

    A new species of the recently revised genus Parosus is described, P. amayae López-García Marín-Gómez sp. nov., from adult and larval specimens collected in bracts of Columnea medicinalis in the Natural Reserve Río Ñambí (Southwestern Colombia). Observations on the interaction with the plant, subsocial behavior, and population density are presented and discussed. Adults and larvae apparently live together and feed on eggs and larvae of flies that develop inside the decomposing fruits of C. medicinalis. The new species is illustrated by color habitus photos, as well as its L1 and L3 larvae, male and female genitalia are depicted by line drawings.

  18. v-erbA overexpression is required to extinguish c-erbA function in erythroid cell differentiation and regulation of the erbA target gene CAII

    DEFF Research Database (Denmark)

    Disela, C; Glineur, C; Bugge, T

    1991-01-01

    The v-erbA oncoprotein represents a retrovirus-transduced oncogenic version of the thyroid hormone (T3/T4) receptor c-erbA (type alpha). It contributes to virus-induced erythroleukemia by efficiently arresting differentiation of red cell progenitors and by suppressing transcription of erythrocyte...... of this CAII reporter construct could only be suppressed by very high amounts of v-erbA. Our results suggest that overexpression of v-erbA is required for its function as an oncoprotein....

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2001-08-08

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

  20. Top-of-atmosphere radiative fluxes - Validation of ERBE scanner inversion algorithm using Nimbus-7 ERB data

    Science.gov (United States)

    Suttles, John T.; Wielicki, Bruce A.; Vemury, Sastri

    1992-01-01

    The ERBE algorithm is applied to the Nimbus-7 earth radiation budget (ERB) scanner data for June 1979 to analyze the performance of an inversion method in deriving top-of-atmosphere albedos and longwave radiative fluxes. The performance is assessed by comparing ERBE algorithm results with appropriate results derived using the sorting-by-angular-bins (SAB) method, the ERB MATRIX algorithm, and the 'new-cloud ERB' (NCLE) algorithm. Comparisons are made for top-of-atmosphere albedos, longwave fluxes, viewing zenith-angle dependence of derived albedos and longwave fluxes, and cloud fractional coverage. Using the SAB method as a reference, the rms accuracy of monthly average ERBE-derived results are estimated to be 0.0165 (5.6 W/sq m) for albedos (shortwave fluxes) and 3.0 W/sq m for longwave fluxes. The ERBE-derived results were found to depend systematically on the viewing zenith angle, varying from near nadir to near the limb by about 10 percent for albedos and by 6-7 percent for longwave fluxes. Analyses indicated that the ERBE angular models are the most likely source of the systematic angular dependences. Comparison of the ERBE-derived cloud fractions, based on a maximum-likelihood estimation method, with results from the NCLE showed agreement within about 10 percent.

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

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    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.

  2. Suppression of atherosclerosis by synthetic REV-ERB agonist

    Energy Technology Data Exchange (ETDEWEB)

    Sitaula, Sadichha [Department of Molecular Therapeutics, The Scripps Research Institute, Jupiter, FL 33458 (United States); Billon, Cyrielle [Department of Pharmacological & Physiological Science, Saint Louis University School of Medicine, St. Louis, MO 63104 (United States); Kamenecka, Theodore M.; Solt, Laura A. [Department of Molecular Therapeutics, The Scripps Research Institute, Jupiter, FL 33458 (United States); Burris, Thomas P., E-mail: burristp@slu.edu [Department of Pharmacological & Physiological Science, Saint Louis University School of Medicine, St. Louis, MO 63104 (United States)

    2015-05-08

    The nuclear receptors for heme, REV-ERBα and REV-ERBβ, play important roles in the regulation of metabolism and inflammation. Recently it was demonstrated that reduced REV-ERBα expression in hematopoetic cells in LDL receptor null mice led to increased atherosclerosis. We sought to determine if synthetic REV-ERB agonists that we have developed might have the ability to suppress atherosclerosis in this model. A previously characterized synthetic REV-ERB agonist, SR9009, was used to determine if activation of REV-ERB activity would affect atherosclerosis in LDL receptor deficient mice. Atherosclerotic plaque size was significantly reduced (p < 0.05) in mice administered SR9009 (100 mg/kg) for seven weeks compared to control mice (n = 10 per group). SR9009 treatment of bone marrow-derived mouse macrophages (BMDM) reduced the polarization of BMDMs to proinflammatory M1 macrophage while increasing the polarization of BMDMs to anti-inflammatory M2 macrophages. Our results suggest that pharmacological targeting of REV-ERBs may be a viable therapeutic option for treatment of atherosclerosis. - Highlights: • Synthetic REV-ERB agonist treatment reduced atherosclerosis in a mouse model. • Pharmacological activation of REV-ERB decreased M1 macrophage polarization. • Pharmacological activation of REV-ERB increased M2 macrophage polarization.

  3. 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...

  4. 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

  5. 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.

  6. Development of an ErbB4 monoclonal antibody that blocks neuregulin-1-induced ErbB4 activation in cancer cells

    International Nuclear Information System (INIS)

    Okazaki, Shogo; Nakatani, Fumi; Masuko, Kazue; Tsuchihashi, Kenji; Ueda, Shiho; Masuko, Takashi; Saya, Hideyuki; Nagano, Osamu

    2016-01-01

    The use of monoclonal antibodies (mAbs) for cancer therapy is one of the most important strategies for current cancer treatment. The epidermal growth factor receptor (EGFR) family of receptor tyrosine kinases, which regulates cancer cell proliferation, survival, and migration, is a major molecular target for antibody-based therapy. ErbB4/HER4, which contains a ligand-binding extracellular region, is activated by several ligands, including neuregulins (NRGs), heparin-binding EGF-like growth factor, betacellulin and epiregulin. Although there are clinically approved antibodies for ErbB1 and ErbB2, there are no available therapeutic mAbs for ErbB4, and it is not known whether ErbB4 is a useful target for antibody-based cancer therapy. In this study, we developed an anti-ErbB4 mAb (clone P6-1) that suppresses NRG-dependent activation of ErbB4 and examined its effect on breast cancer cell proliferation in the extracellular matrix. - Highlights: • We newly generated four clones of human ErbB4 specific mAb. • ErbB4 mAb clone P6-1 blocks ErbB4 phosphorylation induced by NRG-1. • ErbB4 mAb clone P6-1 suppresses NRG-1-promoted breast cancer cells proliferation on three dimensional culture condition.

  7. Development of an ErbB4 monoclonal antibody that blocks neuregulin-1-induced ErbB4 activation in cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Okazaki, Shogo [Division of Gene Regulation, Institute for Advanced Medical Research, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582 (Japan); Nakatani, Fumi [Cell Biology Laboratory, Department of Pharmaceutical Sciences, Faculty of Pharmacy, Kinki University, Higashiosaka, Osaka 577-8502 Japan (Japan); Masuko, Kazue; Tsuchihashi, Kenji [Division of Gene Regulation, Institute for Advanced Medical Research, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582 (Japan); Ueda, Shiho; Masuko, Takashi [Cell Biology Laboratory, Department of Pharmaceutical Sciences, Faculty of Pharmacy, Kinki University, Higashiosaka, Osaka 577-8502 Japan (Japan); Saya, Hideyuki [Division of Gene Regulation, Institute for Advanced Medical Research, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582 (Japan); Nagano, Osamu, E-mail: osmna@sb3.so-net.ne.jp [Division of Gene Regulation, Institute for Advanced Medical Research, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582 (Japan)

    2016-01-29

    The use of monoclonal antibodies (mAbs) for cancer therapy is one of the most important strategies for current cancer treatment. The epidermal growth factor receptor (EGFR) family of receptor tyrosine kinases, which regulates cancer cell proliferation, survival, and migration, is a major molecular target for antibody-based therapy. ErbB4/HER4, which contains a ligand-binding extracellular region, is activated by several ligands, including neuregulins (NRGs), heparin-binding EGF-like growth factor, betacellulin and epiregulin. Although there are clinically approved antibodies for ErbB1 and ErbB2, there are no available therapeutic mAbs for ErbB4, and it is not known whether ErbB4 is a useful target for antibody-based cancer therapy. In this study, we developed an anti-ErbB4 mAb (clone P6-1) that suppresses NRG-dependent activation of ErbB4 and examined its effect on breast cancer cell proliferation in the extracellular matrix. - Highlights: • We newly generated four clones of human ErbB4 specific mAb. • ErbB4 mAb clone P6-1 blocks ErbB4 phosphorylation induced by NRG-1. • ErbB4 mAb clone P6-1 suppresses NRG-1-promoted breast cancer cells proliferation on three dimensional culture condition.

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

    Science.gov (United States)

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

    2014-01-01

    ErbB2 (v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 2), a receptor tyrosine kinase of the ErbB family, is overexpressed in around 25% of breast cancers. In addition to forming a heterodimer with other ErbB receptors in response to ligand stimulation, ErbB2 can be activated in a ligand-independent manner. We report here that Erbin, an ErbB2-interacting protein that was thought to act as an antitumor factor, is specifically expressed in mammary luminal epithelial cells and facilitates ErbB2-dependent proliferation of breast cancer cells and tumorigenesis in MMTV-neu transgenic mice. Disruption of their interaction decreases ErbB2-dependent proliferation, and deletion of the PDZ domain in Erbin hinders ErbB2-dependent tumor development in MMTV-neu mice. Mechanistically, Erbin forms a complex with ErbB2, promotes its interaction with the chaperon protein HSP90, and thus prevents its degradation. Finally, ErbB2 and Erbin expression correlates in human breast tumor tissues. Together, these observations establish Erbin as an ErbB2 regulator for breast tumor formation and progression. PMID:25288731

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

    Directory of Open Access Journals (Sweden)

    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.

  10. Ligand stimulation of ErbB4 and a constitutively-active ErbB4 mutant result in different biological responses in human pancreatic tumor cell lines

    International Nuclear Information System (INIS)

    Mill, Christopher P.; Gettinger, Kathleen L.; Riese, David J.

    2011-01-01

    Pancreatic cancer is the fourth leading cause of cancer death in the United States. Indeed, it has been estimated that 37,000 Americans will die from this disease in 2010. Late diagnosis, chemoresistance, and radioresistance of these tumors are major reasons for poor patient outcome, spurring the search for pancreatic cancer early diagnostic and therapeutic targets. ErbB4 (HER4) is a member of the ErbB family of receptor tyrosine kinases (RTKs), a family that also includes the Epidermal Growth Factor Receptor (EGFR/ErbB1/HER1), Neu/ErbB2/HER2, and ErbB3/HER3. These RTKs play central roles in many human malignancies by regulating cell proliferation, survival, differentiation, invasiveness, motility, and apoptosis. In this report we demonstrate that human pancreatic tumor cell lines exhibit minimal ErbB4 expression; in contrast, these cell lines exhibit varied and in some cases abundant expression and basal tyrosine phosphorylation of EGFR, ErbB2, and ErbB3. Expression of a constitutively-dimerized and -active ErbB4 mutant inhibits clonogenic proliferation of CaPan-1, HPAC, MIA PaCa-2, and PANC-1 pancreatic tumor cell lines. In contrast, expression of wild-type ErbB4 in pancreatic tumor cell lines potentiates stimulation of anchorage-independent colony formation by the ErbB4 ligand Neuregulin 1β. These results illustrate the multiple roles that ErbB4 may be playing in pancreatic tumorigenesis and tumor progression.

  11. ErbB2 resembles an autoinhibited invertebrate epidermal growth factor receptor

    Energy Technology Data Exchange (ETDEWEB)

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

    2009-09-25

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

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    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.

  14. Growth inhibitory effects of the dual ErbB1/ErbB2 tyrosine kinase inhibitor PKI-166 on human prostate cancer xenografts.

    Science.gov (United States)

    Mellinghoff, Ingo K; Tran, Chris; Sawyers, Charles L

    2002-09-15

    Experiments with human prostate cancer cell lines have shown that forced overexpression of the ErbB2-receptor tyrosine kinase (RTK) promotes androgen-independent growth and increases androgen receptor-transcriptional activity in a ligand-independent fashion. To investigate the relationship between ErbB-RTK signaling and androgen in genetically unmanipulated human prostate cancer, we performed biochemical and biological studies with the dual ErbB1/ErbB2 RTK inhibitor PKI-166 using human prostate cancer xenograft models with isogenic sublines reflecting the transition from androgen-dependent to androgen-independent growth. In the presence of low androgen concentrations, PKI-166 showed profound growth-inhibitory effects on tumor growth, which could be partially reversed by androgen add-back. At physiological androgen concentrations, androgen withdrawal greatly enhanced the ability of PKI-166 to retard tumor growth. The level of extracellular signal-regulated kinase activation correlated with the response to PKI-166 treatment, whereas the expression levels of ErbB1 and ErbB2 did not. These results suggest that ErbB1/ErbB2 RTKs play an important role in the biology of androgen-independent prostate cancer and provide a rationale for clinical evaluation of inhibitors targeted to this pathway.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2013-02-01

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

  16. 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.

  17. 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.

  18. 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

  19. REV-ERB and ROR: therapeutic targets for treating myopathies

    Science.gov (United States)

    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.

  20. 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.

  1. Ibrutinib (ImbruvicaTM) potently inhibits ErbB receptor phosphorylation and cell viability of ErbB2-positive breast cancer cells.

    Science.gov (United States)

    Grabinski, Nicole; Ewald, Florian

    2014-12-01

    Ibrutinib (formerly PCI-32765) is a specific, irreversible, and potent inhibitor of Burton's tyrosine kinase (BTK) developed for the treatment of several forms of blood cancer. It is now an FDA-approved drug marketed under the name Imbruvica(TM) (Pharmacyclics, Inc.) and successfully used as an orally administered second-line drug in the treatment of mantle cell lymphoma. Since BTK is predominantly expressed in hematopoietic cells, the sensitivity of solid tumor cells to Ibrutinib has not been analyzed. In this study, we determined the effect of Ibrutinib on breast cancer cells. We demonstrate that Ibrutinib efficiently reduces the phosphorylation of the receptor tyrosine kinases ErbB1, ErbB2 and ErbB3, thereby suppressing AKT and MAPK signaling in ErbB2-positive (ErbB2+) breast cancer cell lines. Treatment with Ibrutinib significantly reduced the viability of ErbB2+ cell lines with IC50 values at nanomolar concentrations, suggesting therapeutic potential of Ibrutinib in breast cancer. Combined treatment with Ibrutinib and the dual PI3K/mTOR inhibitor BEZ235 synergistically reduces cell viability of ErbB2+ breast cancer cells. Combination indices below 0.25 at 50% inhibition of cell viability were determined by the Chou-Talalay method. Therefore, the combination of Ibrutinib and canonical PI3K pathway inhibitors could be a new and effective approach in the treatment of breast cancer with activated ErbB receptors. Ibrutinib could thus become a valuable component of targeted therapy in aggressive ErbB2+ breast cancer.

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

    Directory of Open Access Journals (Sweden)

    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.

  3. 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

  4. [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.

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

    Science.gov (United States)

    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.

  6. 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)

  7. c-erbA and v-erbA modulate growth and gene expression of a mouse glial precursor cell line.

    Science.gov (United States)

    Iglesias, T; Llanos, S; López-Barahona, M; Pérez-Aranda, A; Rodríguez-Peña, A; Bernal, J; Höhne, A; Seliger, B; Muñoz, A

    1994-07-01

    The c-erbA alpha protooncogene coding for the thyroid hormone (T3) receptor (TR alpha 1) and the viral, mutated v-erbA oncogene were expressed in an immortal mouse glial cell line (B3.1) using retroviral vectors. c-erbA alpha expression led to a decrease in cell proliferation in high and low serum conditions, both in the presence and in the absence of T3. In serum-free medium, c-erbA-expressing cells (B3.1 + TR alpha 1) were completely arrested, whereas cells expressing v-erbA (B3.1 + v-erbA) showed a higher DNA synthesis rate than normal B3.1 cells. Although proliferation of all three cell types was stimulated by platelet-derived growth factor and basic fibroblast growth factor, differences were also observed in the response to these agents. B3.1 + TR alpha 1 cells were more sensitive to platelet-derived growth factor than B3.1 and B3.1 + v-erbA cells. In contrast, B3.1 cells responded to basic fibroblast growth factor better than B3.1 + TR alpha 1 or B3.1 + v-erbA cells. Insulin-like growth factor I potentiated the action of platelet-derived growth factor and basic fibroblast growth factor. Again, different responses to treatment with insulin-like growth factor I alone were observed; B3.1 + TR alpha 1 cells did not respond to it, whereas B3.1 + v-erbA cells showed a dramatic stimulation by this agent. Interestingly, in the presence of T3, the blockade in B3.1 + TR alpha 1 cell proliferation was accompanied by the down-regulation of the typical astrocytic genes, glial fibrillary acidic protein and vimentin. These hormone effects were not found in v-erbA-expressing cells. In addition, v-erbA inhibited the basal expression of the cyclic nucleotide phosphodiesterase gene, an oligodendrocytic marker.(ABSTRACT TRUNCATED AT 250 WORDS)

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

    Science.gov (United States)

    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

  9. Role of ErbB receptors in cancer cell migration and invasion

    Directory of Open Access Journals (Sweden)

    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.

  10. 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.

  11. 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.

  12. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  14. 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.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

  17. 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...

  18. 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...

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2011-08-10

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

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

  3. 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...

  4. Dicty_cDB: Contig-U11786-1 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available spleen cDNA, RIKEN full-le... 52 0.057 1 ( EY502489 ) CBBP6397.rev CBBP Hirudo medicinalis hermaphrodit... ...52 0.057 1 ( EY501142 ) CBBP5660.rev CBBP Hirudo medicinalis hermaphrodit... 52 0.057 1 ( EY498689 ) CBBP4264.fwd CBBP Hirudo medicin...alis hermaphrodit... 52 0.057 1 ( EY496087 ) CBBP2702.rev CBBP Hirudo medicina...lis hermaphrodit... 52 0.057 1 ( EY495298 ) CBBP2215.fwd CBBP Hirudo medicinalis herma...phrodit... 52 0.057 1 ( EY486742 ) CBBP15371.rev CBBP Hirudo medicinalis hermaphrodi... 52 0.057 1 ( EY30352

  5. ErbB3 mRNA leukocyte levels as a biomarker for major depressive disorder

    Directory of Open Access Journals (Sweden)

    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.

  6. 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...

  7. 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.

  8. 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

  9. 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 ...

  10. ErbB Proteins as Molecular Target of Dietary Phytochemicals in Malignant Diseases

    Directory of Open Access Journals (Sweden)

    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.

  11. 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)

  12. 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.

  13. 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...

  14. 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...

  15. 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...

  16. 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.

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

    Science.gov (United States)

    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

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

    Directory of Open Access Journals (Sweden)

    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

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

    Science.gov (United States)

    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.

  20. 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

  1. Cannabinoids reduce ErbB2-driven breast cancer progression through Akt inhibition

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  3. 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...

  4. Le vieillard et le chevalier

    Directory of Open Access Journals (Sweden)

    Mélanie JECKER

    2010-05-01

    Full Text Available La fin du Moyen Âge fascine. Deux facteurs principaux expliquent l’attraction qu’exerce cette période : elle apparaît d’une part comme un moment historique riche car double, phase de transition entre le Moyen Âge et la Renaissance, où se mêlent des cadres de représentation anciens et nouveaux. L’insinuation d’une pensée humaniste balbutiante s’y traduirait notamment par l’émergence de la notion d’individu, qui constitue l’un des objets de ce travail. Il faut invoquer, d’autre part, l’image macabre d’un bas Moyen Âge hanté par l’idée de la maladie et de la mort depuis l’épidémie de peste noire de 1348, obsédé par la brièveté de la vie humaine. Ces deux facettes de « l’automne du Moyen Âge » tel que l’évoque avec poésie Joan Huizinga sont-elles autre chose qu’une plaisante image d’Epinal? Cette étude cherche précisément à déterminer le degré de validité de ces deux topiques, à travers l’analyse de la représentation des âges de la vie dans un corpus bien défini, celui de la biographie chevaleresque castillane du XVe siècle. L’intérêt porté à l’individu, la conscience de la singularité impliquent en effet celle du caractère mouvant de la personne, or quel thème mieux que celui des âges permet de confirmer ou d’infirmer l’hypothèse du surgissement d’une nouvelle manière de concevoir l’homme, proprement « renaissante », en ce siècle de transition , La nature même du corpus retenu – des récits biographiques – suggère en effet une mutation dans l’appréhension de la personne, une attention prêtée à sa progressive transformation. L’étude de la représentation de la vieillesse, en particulier, révèle non seulement à quel point était alors réelle cette prétendue obsession de la déchéance physique et de la mortalité, mais aussi dans quelle mesure étaient soulignés et valorisés les changements individuels parallèles à l

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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

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

    Directory of Open Access Journals (Sweden)

    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.

  8. Le beau et le vrai

    Directory of Open Access Journals (Sweden)

    Létitia Mouze

    2006-05-01

    Full Text Available La vie des abeilles de Maeterlinck est un ouvrage à la fois scientifique et littéraire, non pas parce qu’il appartiendrait à la science par son exactitude et à la littérature par son style, mais en ce qu’il invite à penser l’unité des deux domaines. Les aspects littéraires de l’ouvrage (beauté de l’écriture, usage des images, de l’analogie, etc. ne sont pas des accessoires, mais des outils indispensables à l’élaboration d’un authentique savoir sur les abeilles, c’est-à-dire un savoir qui reconnaît la part d’inconnu et le mystère qui subsistent en dépit de toutes les explications physiques et mécaniques que l’on peut par ailleurs donner des phénomènes observés. Etre scientifique, dans cette perspective, c’est-à-dire donner à connaître, c’est donc être littéraire. Cette conception de la science repose en dernière instance sur une conception philosophique de l’univers comme un tout où toutes choses sont reliées, unies, par des relations d’analogies, ce qui fonde et justifie l’emploi d’un style symboliste.The life of bees, one of Maeterlinck’s works, is together a scientific and literary book, not because of it scientific exactness and its literary style, but for the reason it suggests the unity of both these domains. Literay’s aspects of this work (writing’s beauty, use of images, analogy, etc. are not secondary but necessary to elaborate an authentic knowledge about bees, that means a knowledge which admit the unknown part and the mistery that subsist despite all the physical and mechanical explanations we can give moreover about the observed phenomenons. Be a scientist, in this sense, that is give something to know, therefore means be literary. Finally, this conception of science consist in a philosophiacl conception of Universe as a whole where everything links together, and is united by analogical relations, that base and justify the use of a symbolist style.

  9. 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

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

    Science.gov (United States)

    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.

  11. 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

  12. 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.

  13. 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

  14. 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.

  15. 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...

  16. 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

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

    Directory of Open Access Journals (Sweden)

    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.

  18. 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.

    1991-10-01

    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.

  19. 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

  20. 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 ...

  1. [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.

  2. 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

  3. 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

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

    Science.gov (United States)

    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.

  5. 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...

  6. 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.

  7. 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.

  8. 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...

  9. 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

  10. 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.

  11. 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.

  12. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  14. 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.

  15. 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...

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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

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

    Science.gov (United States)

    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

  19. Lele 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 lele des chefs traditionnels au Ghana dans la lutte contre le VIH et le sida. Les collectivités politiques antérieures au colonialisme sont une ...

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    Jesus Eliane C.

    2005-01-01

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

  2. 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...

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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...

  8. 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...

  9. 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...

  10. 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

  11. 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...

  12. 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 ...

  13. 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 ...

  14. 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.

  15. 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.

  16. 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 :.

  17. 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...

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

    Science.gov (United States)

    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.

  19. 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.

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

    Science.gov (United States)

    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.

  1. 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...

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

    Directory of Open Access Journals (Sweden)

    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

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

    Directory of Open Access Journals (Sweden)

    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.

  4. 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

  5. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  7. 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.

  8. 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

  9. 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

  10. 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

  11. 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.

  12. 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.

  13. 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...

  14. 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...

  15. 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.

  16. 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

  17. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  19. Le plurilinguisme du perroquet

    Directory of Open Access Journals (Sweden)

    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 lele 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

  20. 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.

  1. Le charme slave

    Directory of Open Access Journals (Sweden)

    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.

  2. Le Brahmane du Komintern

    Directory of Open Access Journals (Sweden)

    Elizabeth Burgos

    2008-01-01

    Full Text Available Le Brahmane du Komintern, largometraje documental del realizador francés Vladimir León, constituye un ejercicio ejemplar de investigación histórica y  de lograda factura de realización. Y, pese a no haber contado con la ayuda de ninguno organismo público, se trata de un ambicioso proyecto que cubre una amplia extensión geográfica que abarca: Estados Unidos, México, Moscú, Berlín, y la India. Gira en torno a una figura que tuvo en su tiempo su hora de gloria. Un bengalí, hijo de braman, la c...

  3. 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.

  4. Le CRDI au Ghana

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

    pour prévenir le paludisme, des études ayant démontré que leur utilisation pouvait réduire considérablement la mortalité infantile. Les chercheurs ont également suggéré aux gouvernements différents moyens pour inciter les gens à acheter les moustiquaires et à les utiliser correctement. Les TI au service de la démocratie.

  5. Le Culture preistoriche

    OpenAIRE

    Tanda, Giuseppa

    1987-01-01

    Le più antiche manifestazioni della presenza dell'uomo, nella provincia di Sassari (e in Sardegna), risalgono al Quaternario: sono state osservate nel 1979, nel bacino del rio Altana-Anzos, situato nel territorio dei comuni di Laerru e Perfugas. Il presente lavoro propone un excursus dal Paleolitico al Neolitico (antico, medio e recente) fino all'Età del Rame e all'Età del Bronzo (II metà del III millennio-1600 a.C.).

  6. Le CRDI en Chine

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

    les employés du secteur non structuré ont de meilleures conditions de travail. □ les citoyens influencent les décisions relatives aux dépenses publiques. Soutien accordé par le CRDI depuis 1981. 222 activités d'une valeur de 59 millions CAD. Chercheurs et agriculteurs s'emploient à améliorer les moyens de subsistance.

  7. Le CRDI en Tunisie

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

    les citoyens arabes sont plus présents sur Internet. Soutien accordé depuis 1975. 49 activités. 8 millions cad. Dans la foulée du Printemps arabe, les chercheurs conçoivent des réformes visant à assurer l'essor de la démocratie et en examinent la validité. CRDI centre de recherches pour le développement international.

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

    Directory of Open Access Journals (Sweden)

    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].

  9. 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.

  10. 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 ...

  11. 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 ...

  12. 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 ...

  13. 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.

  14. 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)

  15. [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.

  16. 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.

  17. 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

  18. Le regard anachronique

    Directory of Open Access Journals (Sweden)

    Jean-Paul Aubert

    2011-01-01

    Full Text Available Cet article a pour objet l’anachronisme dans le film historique. Il s’appuie sur l’étude du long métrage Goya à Bordeaux, réalisé en 1999 par le cinéaste espagnol Carlos Saura. Cette biographie filmée du peintre Francisco de Goya fait mieux que composer avec l’anachronisme inhérent à toute reconstitution historique. Il l’assume et le revendique. La mise en cause de la chronologie et l’effacement de l’Histoire prennent sens dans la perspective d’une réflexion originale sur l’Histoire de l’art conçue comme un dialogue entre les œuvres et entre les époques.Este artículo está dedicado al problema del anacronismo en las películas históricas. Se basa en el estudio de Goya en Burdeos, un largo metraje rodado en 1999 por el director de cine español Carlos Saura. Esta biografía de Goya no sólo se acomoda con el anacronismo propio de la reconstitución histórica sino que lo asume y lo reivindica. El cuestionamiento de la cronología y el desinterés por la Historia cobran un nuevo sentido en el marco de una reflexión original sobre la Historia del arte concebida como un diálogo entre las obras y entre las épocas.

  19. 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?

  20. Le commerce du Nord

    OpenAIRE

    Pourchasse, Pierrick; Bouëdec, Gérard Le

    2015-01-01

    Au XVIIIe siècle, la France s'approvisionne abondamment dans les pays du Nord : bois, chanvre et goudron de la Baltique, tonnellerie de Poméranie, pêche de rogue de Norvège, graines de lin de Courlande, barres de fer suédois… Sa balance commerciale est pourtant positive grâce aux sels, aux vins et surtout des nouvelles marchandises coloniales. Or, la plupart des transactions passent par l’incontournable intermédiaire hollandais. Les explications sur l’absence des Français dans le Nord sont re...

  1. Le survivant sans le syndrome Schreber

    Directory of Open Access Journals (Sweden)

    Richard Figuier

    2006-09-01

    Full Text Available On a pensé la catastrophe, mais a-t-on suffisamment pensé la survivance et la figure du survivant ? Ce n'est pas un hasard si celle-ci est au centre de Masse et puissance, oeuvre dans laquelle Canetti interroge la « mauvaise » survivance responsable de la poursuite de la logique de guerre. Mais où trouver la « bonne » ? Revenir de la catastrophe ne suffit pas pour être un « survivant authentique », selon l'expression de Kafka. Il faut avoir dépassé, avec Primo Levi et Robert Antelme, l'opposition de la vie comme croissance continue et de la mort comme son horrible contraire, par le don, dans la pauvreté solidaire, de cette vie retrouvée.Hemos reflexionado acerca de la catástrofe, pero ¿hemos meditado lo suficiente sobre la supervivencia y el superviviente? No es una coincidencia si el superviviente es el tema principal de Masse et puissance, obra en la cual Canetti analiza la «mala» supervivencia responsable de la persistencia de la lógica de guerra ¿Dónde sin embargo podemos encontrar la «buena» supervivencia? Superar la catástrofe no es suficiente para ser un «auténtico superviviente», según Kafka. Es fundamental ir más allá, con Primo Levi y Robert Antelme, de la oposición entre la vida, como crecimiento continuo, y la muerte, como su espantoso contrario, mediante la donación de forma solidaria de esta vida reencontrada.Disaster is the theme of many studies, but what about survival and of the figure of the survivor? This issue is central in Mass and power, work in which Canetti questions the “bad” survival, responsible for the continuation of the logic of war. But is there any “good” survival? Coming back from the catastrophe is not enough to be an “authentic survivor”, according to Kafka’s expression. To achieve this, it is necessary to have exceeded, with PrimoLevi and Robert Antelme, the opposition of life as a continuous growth and of death as its horrible opposite, by the gift, in a

  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

    Directory of Open Access Journals (Sweden)

    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

  3. 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 ...

  4. 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

  5. Le tournoi des ombres

    CERN Document Server

    Treille, Daniel

    2017-01-01

    Le lecteur, transporté avec le narrateur dans une région hors norme, est invité à partager sa fascination pour la beauté du lieu, à découvrir la chronique de son passé, rude et pittoresque. Il va côtoyer une galerie de personnages très attachants, mais aux destinées bousculées par l histoire, et assister à l agitation montante du présent dans un contexte d une actualité brûlante. Ce quatrième roman de Daniel Treille, mêlant hardiment les genres, du quotidien trivial au récit épique, de considérations géopolitiques à quelques avancées de la science moderne, confirme son talent à mener, d une écriture très aboutie, une histoire complexe, peuplée de héros singuliers

  6. Le Dominique Interactif

    Directory of Open Access Journals (Sweden)

    Valérie Ouellette

    2005-09-01

    Full Text Available Cet article présente le Dominique Interactif, une bande dessinée interactive et multimédia unique, servant à évaluer sept troubles de la santé mentale chez les jeunes. La version pour les six à onze ans est adaptée aux limites cognitives des enfants et comporte plusieurs avantages. Malgré quelques limites, cet instrument permet d’obtenir des informations fiables de la part de l’enfant sur sa santé mentale. La fidélité et la validité de cet outil sont meilleures que celles des autres instruments traditionnels servant à mesurer la santé mentale des enfants. En combinant les résultats de ce questionnaire avec les informations des parents, professionnels et enseignants, le Dominique Interactif permet aussi d’effectuer une évaluation complète de la santé mentale de l’enfant. Enfin, son utilisation simple et rapide facilite l’évaluation clinique des enfants par les professionnels, permet l’évaluation de programmes d’intervention et favorise l’intervention précoce (Valla et al., 2000.

  7. Le principe roman

    CERN Document Server

    Ferrari, Jérôme

    2015-01-01

    Fasciné par la figure du physicien allemand Werner Heisenberg (1901-1976), fondateur de la mécanique quantique, inventeur du célèbre "principe d'incertitude" et Prix Nobel de physique en 1932, un jeune aspirant-philosophe désenchanté s'efforce, à l'aube du XXIe siècle, de considérer l'incomplétude de sa propre existence à l'aune des travaux et de la destinée de cet exceptionnel homme de sciences qui incarne pour lui la rencontre du langage scientifique et de la poésie, lesquels, chacun à leur manière, en ouvrant la voie au scandale de l'inédit, dessillent les yeux sur le monde pour en révéler la mystérieuse beauté que ne cessent de confisquer le matérialisme à l'œuvre dans l'Histoire des hommes.

  8. 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

  9. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. Le Baratze (ou

    Directory of Open Access Journals (Sweden)

    Jacques Blot

    1998-01-01

    Full Text Available El círculo de piedras Mendizabal 7, de 8 metros de diámetro,   presenta una corona externa constituida de grandes bloques   hincados en la tierra, y otra interna y tangente, de elementos idénticos sólo puestos en el suelo. El cajón central está compuesto de cuatro losas y una tapa. No hay depósito de huesos ni de carbón de leña ; sólo se encuentran dos herraduras, entre las cuales una completa de tipo medieval, que podrían permitir de pensar en una construcción del círculo en el periodo histórico.

  16. Le tourisme alpin

    Directory of Open Access Journals (Sweden)

    Andrea Macchiavelli

    2009-06-01

    Full Text Available La forte croissance qu’ont connue les pays alpins dans les dernières décennies a surtout été fondée sur l’offre des activités du ski, avec comme conséquence, un massif développement immobilier, la multiplication d’infrastructures et l’extension des domaines. Aujourd’hui, le marché du ski semble arriver à saturation, la Convention alpine a mis un frein à la poursuite du développement des domaines skiables et on observe donc avec intérêt la diversification de l’offre soutenue par l’innovation. Après avoir rappelé les facteurs de changement en cours les plus significatifs dans le tourisme montagnard, l’article présente une grille interprétative de l’évolution des destinations touristiques alpines, identifiant les phases qui ont caractérisé son développement. Puis il propose une réflexion sur certaines conditions qui peuvent favoriser l’innovation dans le tourisme alpin, ainsi que sur les contradictions qui les accompagnent souvent. Dans la plupart des cas l’innovation est le résultat d’un processus qui a été lancé et qui s’est développé au sein de la communauté alpine, souvent favorisé et soutenu par des institutions nationales et internationales, et grâce auquel les difficultés structurelles qui ont déjà été abordées précédemment ont pu être surmontées avec succès.The spectacular increase in tourism in the Alps in recent decades has been founded mainly on the boom in skiing, resulting in both strong real estate development and an increasing array of infrastructures and ski runs. Today the ski market seems to have virtually reached saturation point and the winter sports sector needs to diversify its offer through innovation. After a review of the main factors of change in mountain tourism, the paper presents a grid for interpreting the life cycle of alpine destinations, identifying the phases that characterize their evolution. The conditions that may favour innovation in alpine

  17. Le citoyen rieur

    Directory of Open Access Journals (Sweden)

    Anna Rycman

    2009-11-01

    Full Text Available Dans la Pologne d’aujourd’hui, l’évolution des modèles d’engagement civique et politique s’opère plus particulièrement auprès des jeunes générations. Parmi les expériences nouvelles de participation politique, les nouvelles technologies de l’information et de la communication offrent des opportunités radicales de reconfigurer l’espace public. La jeunesse polonaise investit en masse le Web. Dans le flux de paroles affranchies circulant et dialoguant dans le cyberespace, nous nous intéressons ici au développement d’un discours qui emprunte au registre de la dérision et de la satire politiques. Une multitude de sites critiques, de nature apparemment contestataire, des sites d’opposition fondés sur le genre satirique, ont émergé comme réponse apportée à la situation politique. Cet espace public électronique représente une forme moderne de « folklore politique », contribuant au processus de socialisation des jeunes citoyens polonais.The laughing citizen. A modern form of civic commitment in democratic Poland?In present day Poland, the evolution of civic and political commitment models is above all the affaire of the younger generations. Among the current opportunities for political participation, the new information and communication technologies offer radical opportunities to reconfigure the public arena. Polish youth are flocking to the Web. Amongst the flux of frank points of views circulating and dialoguing in cyberspace, our interest here is the development of a discourse inspired by political and satirical derision. A multitude of critical, apparently anti-establishment, sites and general opposition sites using the satirical style have emerged as a response to the political situation. This public electronic space represents a modern form of « political folklore », contributing to the socialising processes of young polish citizens.El ciudadano que rie. ¿Nueva forma del compromiso cívico en la

  18. Le grand inventaire

    Directory of Open Access Journals (Sweden)

    Michel Melot

    2012-05-01

    Full Text Available Depuis quarante ans qu’il existe, l’Inventaire général des monuments et des richesses artistiques de la France n’a pas seulement progressé, couvrant près de dix mille communes, documentant plus de vingt mille dans cinq millions de pages, trois millions de photographies, et cent mille dessins. Il est devenu ce que ses fondateurs désiraient qu’il fût. Il n’est pas une liste d’objets plus ou moins singuliers qu’on aurait oubliés, mais l’observation méthodique de l’émergence dans le monde de l’ar...

  19. 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).

  20. 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...

  1. 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...

  2. 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 ...

  3. 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

  4. 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.

  5. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  7. 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

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

    Directory of Open Access Journals (Sweden)

    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

  9. 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

  10. 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...

  11. Le bal du loup

    CERN Multimedia

    Happy Children's Home

    2013-01-01

    The Bord'eau amateur theatre group will graciously perform a play of their creation Le bal du loup Saturday 19 October 2013 at 20:00 Sunday 20 October at 17:00 in the Théâtre des Grottes Rue Louis Favre 43, 1201 Genève Children from age 12 upwards. Summary: The new-elected mayoress of a small village would like to clean up the town by prohibiting alcohol and getting rid of its prostitutes. Then along comes « Massimo Lupo » the pimp... The performances will be given to support the Happy Children's Home charity, which runs a foster-home in Pokhara for Nepali children:  http://www.happychildrenshome.org/ Admission : minimum charge of 10 CHF per person requested, to cover the cost of technical assistance and theatre rental. Any profit will be used solely for the foster-home. At the end of each performance members of the HCH charity will be happy to answer any questions you may have. The theatre has 86 seats, thank you for reserv...

  12. 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)

  13. 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.

  14. 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.

  15. 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...

  16. Lele 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 .

  17. 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 ...

  18. Lele 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. Lele des fournisseurs de ... Climate Change and Water Adaptation Options. The impacts of climate ...

  19. Le dualisme Chipaya

    Directory of Open Access Journals (Sweden)

    1974-01-01

    Full Text Available L’auteur, partant des observations de Métraux sur Chipaya, apporte des idées neuves sur les ayllu constituant le village, basées sur une enquête approfondie et un plan détaillé du village : deux divisions principales apparaissent, celles-ci se divisant a leur tour en quatre ayllu. La chute brutale de la démographie depuis la seconde moitié du XVIe siècle a fait disparaître les 4 ayllu originels mais l’examen des archives permet d’observer un très vigoureux redressement démographique à partir des derniers 150 ans. Ce redressement démographique semble précipiter un nouvel éclatement de la communauté chipaya. El autor partiendo de las observaciones de Métraux sobre Chipaya, aporta sobre los ayllu que constituían el pueblo, basadas en una encuesta profunda y un plano detallado del pueblo: aparecen dos divisiones principales, dividiéndose éstas a su vez en cuatro ayllu. La caída brutal de la demografía desde la segunda mitad del siglo XVI ha hecho desaparecer los 4 ayllu primitivos pero el examen de los archivos permite observar un resurgimiento vigoroso a partir de los últimos 150 años. Este resurgimiento demográfico parece precipitar una nueva explosión de la comunidad chipaya.

  20. 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 lele de Kastler dans son époque, et décrit sa personnalité généreuse à travers ses r

  1. 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

  2. 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

  3. 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...

  4. 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.

  5. 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...

  6. 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

  7. 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

  8. 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

  9. 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)

  10. 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

  11. 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 ...

  12. 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

  13. 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

  14. 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.

  15. 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 lele de l’inventaire qui, en mettant en œuvre une démarche systématique de connaissance, participe à l’ identificatio...

  16. Le Corbusier’s Dioramas

    Directory of Open Access Journals (Sweden)

    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

  17. 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...

  18. 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.

  19. Le chrome en milieu marin

    OpenAIRE

    Chiffoleau, Jean-francois

    1994-01-01

    Le présent document constitue une synthèse des connaissances sur le cycle biogéochimique du chrome. Les sources naturelles et anthropiques sont étudiées, les échanges entre les différents compartiments géochimiques sont évalués, avec une attention particulière portée à la quantification des apports aussi bien des fleuves que de l'atmosphère au milieu marin. Les niveaux de concentration dans ces compartiments sont évalués, et montrent que l'on rencontre dans certaines régions des contamination...

  20. Agir sur le gaspillage alimentaire

    OpenAIRE

    Jan, Sophie; Baron, Florence

    2016-01-01

    On estime aujourd'hui à 25% les pertes d'aliments post-récolte et en aval, en raison de leur altération par des microorganismes. L'étude menée ici illustre le risque d'altération engendré par une rupture dans la chaîne du froid, en prenant comme modèle un aliment liquide pasteurisé et réfrigéré, riche en nutriments et dont la température ne doit pas dépasser 4°C.

  1. 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

  2. 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].

  3. 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.

  4. 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 ...

  5. 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 ...

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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)

  12. 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.

  13. 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

  14. 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.

  15. 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...

  16. 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...

  17. 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...

  18. 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

  19. 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.

  20. 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...

  1. Bulletin #109 | CRDI - Le Centre de recherches pour le ...

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

    ... offres d'emploi. Appel à propositions de recherche sur les villes résilientes en Amérique latine. Date butoir : 13 juin 2016. Programme de recherche sur le virus Zika Canada-Amérique latine et Caraïbes Date butoir : 12 juillet 2016. POSSIBILITÉS D'EMPLOIS Agent de ressources humaines · Analyste des opérations de TI.

  2. Vaincre le vampire violet | CRDI - Centre de recherches pour le ...

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

    26 janv. 2011 ... ... de s'assurer que l'arme fongique découverte par Alan Watson ne se transforme en mercenaire et cause la destruction d'autres espèces végétales, Fusarium oxysporum a été soumis pendant deux ans à une batterie de tests dans les laboratoires hautement sécurisés de McGill, sur le campus Macdonald.

  3. Le futur du travail | CRDI - Centre de recherches pour le ...

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

    12 juin 2017 ... Trois hommes qui travaillent sur le projet de livraison de drone au Rwanda. Sarah Farhat / Banque mondiale. La numérisation, l'automatisation et les communications en réseau façonnent de plus en plus les sociétés, les marchés du travail et les occasions d'emploi à l'échelle mondiale. Les changements ...

  4. Le colonel Rol-Tanguy

    OpenAIRE

    Bourderon, Roger

    2009-01-01

    Ouvrier métallurgiste, syndicaliste et communiste, le futur colonel Rol-Tanguy, né en 1908, se passionne pour le métier des armes lors de son service militaire. Son expérience dans les Brigades internationales est décisive. Il l’enrichit dans les FTP puis comme chef régional FFI : il prépare et conduit l’insurrection parisienne avec un état-major comportant de nombreux cadres de l’armée. Compagnon de la Libération, il se distingue dans la campagne d’Allemagne et est intégré dans l’armée avec ...

  5. Le glaive de la parole

    Directory of Open Access Journals (Sweden)

    Luce Marchal-Albert

    2006-09-01

    Full Text Available Chacun sait, selon le mot de Pierre Viret, « en quelle confusion est la Chrestienté » au xvie siècle en Europe. C’est le deuxième quart du siècle qui nous intéressera ici, et en particulier l’année 1545, qui constitue une année charnière qui voit vaciller l’Église romaine, flamber et culminer la chasse aux hérétiques en même temps qu’elle voit la jeune Église réformée se renforcer et se positionner avec succès dans un champ religieux plus que chaotique. Les ouvrages polémiques réformés écrits...

  6. Le CRDI au Costa Rica

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

    région ont-elles besoin du commerce, mais elles doivent en outre acquérir de nouvelles compétences afin de pouvoir prospérer dans l'économie du savoir. La capacité d'utiliser les technologies de l'information, entre autres, est désormais une nécessité. Le CRDI subventionne la Fundación. Omar Dengo afin qu'elle puisse ...

  7. Georges et le big bang

    CERN Document Server

    Hawking, Lucy; Parsons, Gary

    2011-01-01

    Georges et Annie, sa meilleure amie, sont sur le point d'assister à l'une des plus importantes expériences scientifiques de tous les temps : explorer les premiers instants de l'Univers, le Big Bang ! Grâce à Cosmos, leur super ordinateur, et au Grand Collisionneur de hadrons créé par Éric, le père d'Annie, ils vont enfin pouvoir répondre à cette question essentielle : pourquoi existons nous ? Mais Georges et Annie découvrent qu'un complot diabolique se trame. Pire, c'est toute la recherche scientifique qui est en péril ! Entraîné dans d'incroyables aventures, Georges ira jusqu'aux confins de la galaxie pour sauver ses amis...Une plongée passionnante au coeur du Big Bang. Les toutes dernières théories de Stephen Hawking et des plus grands scientifiques actuels.

  8. 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.

  9. 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.

  10. 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

  11. 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

  12. 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.

  13. 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

  14. Le principe non bis in idem et le droit communautaire

    OpenAIRE

    Hedabou, Aziz

    2018-01-01

    Le principe non bis in idem est une garantie fondamentale qui interdit que les mêmes faits soit poursuivi et puni deux fois. Il est reconnu par tous les droits internes et “appartient aux droit universel des nations”. Dès lors, sa lettre et son esprit ne sont plus cantonnés au droit interne et ont tendance à s’internationaliser. En droit communautaire, l’étude du principe non bis in idem peut être envisagée sous trois angles différents. D’abord en droit pénal international unilatéral où chaqu...

  15. Le tennis dans le monde: état et prospective

    Directory of Open Access Journals (Sweden)

    Pierre DUMOLARD

    1989-06-01

    Full Text Available Le tennis est peu ou prou pratiqué dans tous les pays du monde, mais avec de considérables variations d'intensité. Actuellement, ses points d'ancrage se situent dans les pays développés occidentaux et dans l'ancienne sphère d'influence britannique. En tenant compte de l'évolution démographique et économique possible des nations, des projections de pénétration de ce sport sont établies pour l'horizon 2000.

  16. 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.

  17. 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.

  18. 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

  19. 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

  20. 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

  1. 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 ...

  2. 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 ...

  3. 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), ...

  4. 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 ...

  5. Lele du langage de programmation dans la réalisation de code ...

    African Journals Online (AJOL)

    Lele du langage de programmation dans la réalisation de code de qualité, les cas de Delphi et C++ Nous discutons dans ce papier lele 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 ...

  6. La spermiation chez le brochet.

    Directory of Open Access Journals (Sweden)

    DE MONTALEMBERT G.

    1980-01-01

    Full Text Available L'évolution quantitative et qualitative de la production de sperme au cours de la période de spermiation a été étudiée chez des brochets maintenus en captivité dans un étang de 400 m2. Le sperme est prélevé toutes les semaines à partir du début de février, et pendant près de 2 mois. La quantité de sperme recueillie est très faible et présente de fortes variations individuelles ; elle augmente progressivement jusqu'à la 5me semaine et décroit ensuite. La quantité moyenne de sperme récoltée par mâle est de l'ordre de 0,7 ml/semaine et varie considérablement d'un mâle à l'autre (0.07 à 1,5 ml. La concentration du sperme en spermatozoïdes varie entre 18 et 25 milliards par ml ( X = 21,5 109 + 2,11. La quantité de spermatozoïdes récoltée par semaine est de 28,5 106 + 26,4/kg de poids corporel. La qualité du sperme appréciée par l'intensité et la durée de motilité suit une évolution similaire à celle de la quantité de sperme récoltée avec des valeurs maximales à 4 semaines et minimales en début et fin de période de prélèvement. Les premières ovulations détectées sur des femelles stockées dans les mêmes conditions que les mâles ont été observées à la 6me semaine de prélèvements alors que les performances de spermiation avaient déjà fortement déclinées. Il est vraisemblable que les conditions expérimentales particulièrement traumatisantes pour les mâles ont affecté prématurément la spermiation, amplifiant ainsi le décalage fréquemment observé entre les périodes de spermiation et d'ovulation.

  7. Le groupe de travail EPNAC

    Directory of Open Access Journals (Sweden)

    MOLLE, Pascal

    2012-12-01

    Full Text Available En France, les procédés de traitement des eaux usées des petites et moyennes collectivités sont en constante évolution et leur diversité augmente fortement. Constitué à l'initiative d'Irstea, le groupe de travail EPNAC a pour objectif de mutualiser et de diffuser une information technique et cohérente sur ces procédés auprès des acteurs de l'assainissement.

  8. 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 ...

  9. 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.

  10. 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, ...

  11. 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.

  12. 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.

  13. 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...

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

    Directory of Open Access Journals (Sweden)

    Richard L. Schroeder

    2014-09-01

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

  15. Alterations in cell growth and signaling in ErbB3 binding protein-1 (Ebp1 deficient mice

    Directory of Open Access Journals (Sweden)

    Lee Myounghee

    2008-12-01

    Full Text Available Abstract Background The ErbB3 binding protein-1 (Ebp1 belongs to a family of DNA/RNA binding proteins implicated in cell growth, apoptosis and differentiation. However, the physiological role of Ebp1 in the whole organism is not known. Therefore, we generated Ebp1-deficient mice carrying a gene trap insertion in intron 2 of the Ebp1 (pa2g4 gene. Results Ebp1-/- mice were on average 30% smaller than wild type and heterozygous sex matched littermates. Growth retardation was apparent from Day 10 until Day 30. IGF-1 production and IGBP-3 and 4 protein levels were reduced in both embryo fibroblasts and adult knock-out mice. The proliferation of fibroblasts derived from Day 12.5 knock out embryos was also decreased as compared to that of wild type cells. Microarray expression analysis revealed changes in genes important in cell growth including members of the MAPK signal transduction pathway. In addition, the expression or activation of proliferation related genes such as AKT and the androgen receptor, previously demonstrated to be affected by Ebp1 expression in vitro, was altered in adult tissues. Conclusion These results indicate that Ebp1 can affect growth in an animal model, but that the expression of proliferation related genes is cell and context specific. The Ebp1-/- mouse line represents a new in vivo model to investigate Ebp1 function in the whole organism.

  16. 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

  17. 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.

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

    African Journals Online (AJOL)

    Notre contribution porte sur lele 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 ...

  19. Le language des masques burkinabè

    African Journals Online (AJOL)

    hond

    2 juil. 2007 ... un faire transformateur cognitif devient un esprit qui a des fonctions hautement spirituelles, religieuses et aussi souvent esthétiques. Le langage et le discours des masques. Les masques sont un langage et un discours. Un langage est un système de communi- cation et d'expression. L'unité de base de ...

  20. 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

  1. 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;

  2. 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.

  3. 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.

  4. Le projet de station touristique

    OpenAIRE

    Vlès, Vincent

    1996-01-01

    Cet ouvrage traite du savoir-faire du technicien, de l'ingénieur, du directeur d'office de tourisme qui façonne, depuis maintenant près de trois décennies, le territoire local de la production touristique : la station. Il analyse les stratégies, les mises en œuvre, les pratiques de l'aménagement et du développement touristique. Il propose une construction du projet de station, méthode qui est l'aboutissement d'expériences de terrain. Il présente un guide des interventions. Il décrit des modes...

  5. Le Squatteur, le Gentrifieur et le Promoteur. Une leçon de la géographie

    Directory of Open Access Journals (Sweden)

    Laurent Matthey

    2005-03-01

    Full Text Available Posées sur mon bureau : deux photos. Je les regarde. Silencieusement, je les décris et les commente. La première a été prise en novembre 1997. Angle rue Jean-Violette, rue Prévost-Martin, à Genève. On y voit un immeuble, ancien, des échafaudages. Entre cet immeuble et celui qui lui fait face, on a tendu des fanions verts, bleus, orange. Son rez-de-chaussée a été repeint dans une teinte un peu brique. La seconde date d’avril 2005. C’est le même immeuble, presque dix ans plus tard, rénové. Jaun...

  6. 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

  7. 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

  8. 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

  9. 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.

  10. CERES ERBE-like Monthly Regional Averages (ES-9) in HDF (CER_ES9_TRMM-PFM_Edition1)

    Science.gov (United States)

    Wielicki, Bruce A. (Principal Investigator)

    The ERBE-like Monthly Regional Averages (ES-9) product contains a month of space and time averaged Clouds and the Earth's Radiant Energy System (CERES) data for a single scanner instrument. The ES-9 is also produced for combinations of scanner instruments. All instantaneous shortwave and longwave fluxes at the Top-of-the-Atmosphere (TOA) from the CERES ES-8 product for a month are sorted by 2.5-degree spatial regions, by day number, and by the local hour of observation. The mean of the instantaneous fluxes for a given region-day-hour bin is determined and recorded on the ES-9 along with other flux statistics and scene information. For each region, the daily average flux is estimated from an algorithm that uses the available hourly data, scene identification data, and diurnal models. This algorithm is 'like' the algorithm used for the Earth Radiation Budget Experiment (ERBE). The ES-9 also contains hourly average fluxes for the month and an overall monthly average for each region. These average fluxes are given for both clear-sky and total-sky scenes. The following CERES ES9 data sets are currently available: CER_ES9_FM1+FM2_Edition1 CER_ES9_PFM+FM1+FM2_Edition1 CER_ES9_PFM+FM1+FM2_Edition2 CER_ES9_PFM+FM1_Edition1 CER_ES9_PFM+FM2_Edition1 CER_ES9_PFM+FM1_Edition2 CER_ES9_PFM+FM2_Edition2 CER_ES9_TRMM-PFM_Edition1 CER_ES9_TRMM-PFM_Edition2 CER_ES9_Terra-FM1_Edition1 CER_ES9_Terra-FM2_Edition1 CER_ES9_FM1+FM2_Edition2 CER_ES9_Terra-FM1_Edition2 CER_ES9_Terra-FM2_Edition2 CER_ES9_Aqua-FM3_Edition1 CER_ES9_Aqua-FM4_Edition1 CER_ES9_FM1+FM2+FM3+FM4_Edition1 CER_ES9_Aqua-FM3_Edition2 CER_ES9_Aqua-FM4_Edition2 CER_ES9_FM1+FM3_Edition2 CER_ES9_FM1+FM4_Edition2 CER_ES9_Aqua-FM3_Edition1-CV CER_ES9_Aqua-FM4_Edition1-CV CER_ES9_Terra-FM1_Edition1-CV CER_ES9_Terra-FM2_Edition1-CV. [Location=GLOBAL] [Temporal_Coverage: Start_Date=1998-01-01; Stop_Date=1998-08-31] [Spatial_Coverage: Southernmost_Latitude=-90; Northernmost_Latitude=90; Westernmost_Longitude=-180; Easternmost

  11. CERES ERBE-like Instantaneous TOA Estimates (ES-8) in HDF (CER_ES4_TRMM-PFM_Edition1)

    Science.gov (United States)

    Wielicki, Bruce A. (Principal Investigator)

    The ERBE-like Monthly Geographical Averages (ES-4) product contains a month of space and time averaged Clouds and the Earth's Radiant Energy System (CERES) data for a single scanner instrument. The ES-4 is also produced for combinations of scanner instruments. For each observed 2.5-degree spatial region, the daily average, the hourly average over the month, and the overall monthly average of shortwave and longwave fluxes at the Top-of-the-Atmosphere (TOA) from the CERES ES-9 product are spatially nested up from 2.5-degree regions to 5- and 10-degree regions, to 2.5-, 5-, and 10-degree zonal averages, and to global monthly averages. For each nested area, the albedo and net flux are given. For each region, the daily average flux is estimated from an algorithm that uses the available hourly data, scene identification data, and diurnal models. This algorithm is 'like' the algorithm used for the Earth Radiation Budget Experiment (ERBE). The following CERES ES4 data sets are currently available: CER_ES4_FM1+FM2_Edition1 CER_ES4_PFM+FM1+FM2_Edition1 CER_ES4_PFM+FM1+FM2_Edition2 CER_ES4_PFM+FM1_Edition1 CER_ES4_PFM+FM2_Edition1 CER_ES4_TRMM-PFM_Edition1 CER_ES4_TRMM-PFM_Edition2 CER_ES4_Terra-FM1_Edition1 CER_ES4_Terra-FM2_Edition1 CER_ES4_FM1+FM2_Edition2 CER_ES4_Terra-FM1_Edition2 CER_ES4_Terra-FM2_Edition2 CER_ES4_Aqua-FM3_Edition1 CER_ES4_Aqua-FM4_Edition1 CER_ES4_FM1+FM2+FM3+FM4_Edition1 CER_ES4_Aqua-FM3_Edition2 CER_ES4_Aqua-FM4_Edition2 CER_ES4_FM1+FM3_Edition2 CER_ES4_FM1+FM4_Edition2 CER_ES4_PFM+FM1_Edition2 CER_ES4_PFM+FM2_Edition2 CER_ES4_Aqua-FM3_Edition1-CV CER_ES4_Aqua-FM4_Edition1-CV CER_ES4_Terra-FM1_Edition1-CV CER_ES4_Terra-FM2_Edition1-CV. [Location=GLOBAL] [Temporal_Coverage: Start_Date=1998-01-01; Stop_Date=1998-08-31] [Spatial_Coverage: Southernmost_Latitude=-90; Northernmost_Latitude=90; Westernmost_Longitude=-180; Easternmost_Longitude=180] [Data_Resolution: Latitude_Resolution=2.5 degree; Longitude_Resolution=2.5 degree; Horizontal

  12. 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 ...

  13. 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...

  14. Le Corbusier, Alfred Roth y el color

    Directory of Open Access Journals (Sweden)

    Angelica Fernández-Morales

    2014-07-01

    Full Text Available This article discusses the relationship between Le Corbusier and Alfred Roth, a member of the Paris office between 1927 and 1928. It also deals with the influence that this period had with reference to an important factor in Roth’s professional development, as in Le Corbusier’s later works: the use of colour in his architecture. This article takes the position that Roth, given his close friendship with Mondrian, was an important figure in turning Le Corbusier’s work towards greater use of primary colours and aesthetic neoplasticism.

  15. Le soleil devient un mythe

    Directory of Open Access Journals (Sweden)

    Ildikó Lőrinszky

    2009-01-01

    Full Text Available Partant d’une phrase énigmatique datant de 1858 et puisée dans la Correspondance de Flaubert, cet article s’interroge sur la relation entre soleil et mythe, qui constituera l’un des éléments clefs de la dimension mythologique de Salammbô. Il se propose d’examiner la façon dont cette question apparaît dans deux ouvrages représentatifs des études mythographiques : d’une part, L’Origine de tous les cultes de Charles-François Dupuis, d’autre part, Les Religions de l’Antiquité..., publié sous les noms de Frédéric Creuzer et de son adaptateur français, Joseph-Daniel Guigniault. La version française de la grande synthèse de Creuzer, assortie d’une série importante de planches, a été richement exploitée par Flaubert au cours de la genèse du roman carthaginois. Dans Salammbô, le mythe apparaît sous de multiples formes. L’analyse de ce texte peut nous amener à réfléchir sur le « bon usage » du mythe auquel chaque créateur (et chaque lecteur se trouve nécessairement confronté.Starting from an enigmatic phrase in Flaubert’s correspondence, dating from 1858, this article examines the relation between the Sun and myth, which constitutes one of the key elements of the mythological dimension of Salammbô. It especially focuses on the treatment of this question in two representative works of mythographic studies, The Origin of All Religious Worship by Charles-François Dupuis, and Les Religions de l’Antiquité..., the French adaptation of Frédéric Creuzer’s Symbolik und Mythologie der alten Völker by Joseph-Daniel Guigniault. The French version of Creuzer’s great synthesis, supplied with a remarkable set of prints, was abundantly consulted by Flaubert when writing his Carthaginian novel. In Salammbô, myth takes on various forms. Analyzing this text might lead one to reconsider “the right way” to use myths — a problem all writers (and readers find themselves confronted with.

  16. 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.

  17. 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.

  18. 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...

  19. 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.

  20. 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).

  1. 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).

  2. 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.

  3. 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.

  4. Jan Potocki et le "Gothic Novel"

    Science.gov (United States)

    Finne, Jacques

    1970-01-01

    Establishes a parallel between the supernatural and fantastic qualities of Le Comte Jan Potocki's literary works, and the English gothic novels by comparing the elements of terror, mysterious atmosphere, and the supernatural beings involved. (DS)

  5. Original Paper Le champignon arbusculaire Glomus aggregatum ...

    African Journals Online (AJOL)

    Le champignon arbusculaire Glomus aggregatum améliore la nutrition minérale de ... Salinity remains a major problem for soil fertility, especially in the Sahelian zone. However, many ...... environmental gradient in the Brazilian semiarid.

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

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

    le 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 ...

  7. 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 : ...

  8. Nuevo León

    Directory of Open Access Journals (Sweden)

    Laura Nelly Medellín Mendoza

    2006-01-01

    Full Text Available El ensayo analiza la transición política nuevoleonesa a partir de un contexto de liberalización política. En Nuevo León el régimen político autoritario fue cediendo en el plano electoral, dada la presión que conjuntamente la sociedad política y la sociedad civil ejercieron por lograr reglas democráticas. Este avance gradual permitió garantizar un organismo electoral confiable y que determinó en buena medida la garantía de la alternancia en 1997. El pan fue el partido que capitalizó el bono democrático, pero una vez en la responsabilidad de gobierno, no pudo ampliar el proceso de liberalización política al mediatizar las reformas electorales y no comprometerse para sacar del atolladero legislativo las iniciativas que garantizaban mecanismos de participación ciudadana: referéndum y plebiscito.

  9. Le Chatelier principle in replicator dynamics

    OpenAIRE

    Allahverdyan, Armen E.; Galstyan, Aram

    2011-01-01

    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 Nas...

  10. Le CRDI au Brésil

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

    Les recherches subventionnées par le CRDI au Brésil ont permis d'éclairer les débats sur nombre de questions, dont la démocratie, la croissance économique, la santé, les services sociaux, l'innovation, la foresterie et l'eau. Pendant la dictature militaire, qui a pris fin en 1985, le CRDI s'est employé à assurer la survie de la ...

  11. Le CRDI en Cisjordanie et à Gaza

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

    Stress des adolescents et conflit qui perdure. En Cisjordanie, la violence politique et le conflit qui perdure ont aggravé le stress chez les adolescents, qui constituent près de la moitié de la population. À Ramallah, plus de 3 000 adolescents de 15 à 17 ans ont été interrogés par des chercheurs de l'Université de Birzeit et de ...

  12. Le désordre du monde

    African Journals Online (AJOL)

    sulaiman.adebowale

    Le début du XXIe siècle se caractérise par l'accumulation et la consécution ..... Unis a présidé à la naissance aux forceps de cet outil d'équilibre du monde en ... De toute évidence, l'ONU reste l'instrument qui a marqué le siècle dernier,.

  13. la lutte contre le SIDA au Cameroun

    African Journals Online (AJOL)

    Chantel

    Pour lutter contre cette pandémie, le Cameroun s'est organisé en mettant en place, avec l'aide de ses partenaires bilatéraux et ... la dérision qui faisait du SIDA 'le syndrome inventé pour décourager les ... rapidement donner une réponse médicale à la maladie. ... histoire politique, à ses susceptibilités historiques et à.

  14. LE MARCHE FINANCIER EN ALGERIE : SITUATION ET ...

    African Journals Online (AJOL)

    Administrateur

    marché en l'occurrence le marché financier ne représente pas un problème strictement ... variés de par le monde. Dans les pays en transition, la performance du .... Les valeurs mobilières sont constituées de deux types de titres : les titres de .... La COSOB (commission d'organisation et de surveillance des opérations de ...

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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...

  1. 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)

  2. Le concept d’ethos.

    Directory of Open Access Journals (Sweden)

    Bernard Fusulier

    2011-09-01

    Full Text Available Dans cet article, l’auteur traite de la signification et de l’usage du concept d’ethos. Dans la sociologie classique, ce dernier a été utilisé pour comprendre et qualifier la rationalité socialement et éthiquement encastrée des conduites sociales. Exprimant l’intériorisation d’un principe organisateur de pratiques, dessinant une matrice globale des comportements, il est porteur d’une vision qui paraît datée à l’heure du “brouillage des classes sociales”, de la “modernité liquide” et de “l’homme pluriel”. Néanmoins, si l’on reconnaît l’existence d’un univers social non entièrement liquéfié, c’est-à-dire où continuent à exister des milieux sociaux sédimentés qui imprègnent avec plus ou moins de profondeur le système de personnalité de celui qui s’y insère durablement, l’ethos reste un concept heuristique pour saisir et interpréter les récurrences de comportements qui peuvent s’y observer. Permettant de comprendre ce que les espaces d’insertion “font aux individus” ainsi que la façon dont les principes organisateurs de pratiques entrent en transaction (en consonance, en dissonance ou en concurrence, il garde toute sa pertinence dans la boîte à outils théoriques du sociologue et de l’anthropologue d’aujourd’hui.

  3. 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

  4. 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

  5. Konversion des kulturellen Erbes für die Forschung: Volltextbeschaffung und -bereitstellung als Aufgabe der Bibliotheken

    Directory of Open Access Journals (Sweden)

    Thomas Stäcker

    2014-12-01

    Full Text Available Mit der Transformation des gedruckten Buch zum elektronischen Text verändern sich zentrale Rahmenbedingungen der Bibliothek. Die theoretischen Grundlagen des ‚Buches‘ müssen unter dem Gesichtspunkt des Digitalen neu durchdacht und auf ihre praktischen Konsequenzen hin geprüft werden. Vor allem die Transitivität, spezifische Schriftlichkeit und Prozessierbarkeit elektronischer Texte sind Eigenschaften, die Konsequenzen für eine ganze Reihe bibliothekarischer Kernaufgaben haben. Mit Blick auf das kulturelle Erbe, das in Bibliotheken verwahrt wird, stellt sich die Aufgabe, auf diesen Paradigmenwechsel angemessen zu reagieren und Sorge dafür zu tragen, dass das schriftliche und gedruckte Kulturgut auch in einer adäquaten maschinenlesbaren Form zur Verfügung steht. Nach gut 10 Jahren erfolgreicher Imagedigitalisierung muss daher jetzt, nach der Entwicklung entsprechender Techniken der nächste Schritt zur Herstellung, Aufbereitung und Bereitstellung von Volltext getan werden, um neuen, sich aus der digitalen Wende ergebenden Forschungsanforderungen und Forschungsfragen, die sich mit Begriffen wie Stilometrie, Clusteranalyse, Topic Modeling etc. verbinden, zu genügen. Den Bibliotheken wächst vor diesem Hintergrund in der Transformation des schriftlichen Kulturgutes und Bereitstellung von Volltexten eine neue Aufgabe zu. Sie können darin einen wichtigen Beitrag zum Aufbau einer Infrastruktur für eine digital arbeitende Geistes- und Kultwissenschaft bzw. die Digital Humanities leisten. The transformation of the book into an electronic text has led to constitutive changes in the functional frameworks of the library. Basic concepts of the notion of the ‘book’ have to be reconsidered and to be evaluated in view of the practical consequences. Above all, the transitivity of such texts, the specific mode of writing employed, and their ability to be processed are aspects that have considerable impact on several core tasks of the library. In

  6. 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 ...

  7. 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 ...

  8. 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.

  9. 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.

  10. 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 ...

  11. 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 ...

  12. 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 ...

  13. 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.

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

    Directory of Open Access Journals (Sweden)

    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

  15. 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...

  16. 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...

  17. Lele 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...

  18. 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...

  19. 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.

  20. 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].

  1. 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].

  2. 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].

  3. 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].

  4. 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].

  5. 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...

  6. Gisèle HALIMI, La Kahina

    OpenAIRE

    ALLOUCHE-BENAYOUN, Joëlle

    2010-01-01

    Est-ce un ouvrage historique ? Est-ce un roman ? Un roman historique ? Le lecteur est désemparé dès qu’il plonge dans l’ouvrage que Gisèle Halimi a consacré à la grande héroïne judéo berbère. Si l’on comprend bien l’intérêt de l’avocate féministe – par ailleurs juive et née en Tunisie – pour cette figure féminine de résistance, la gêne s’installe au fur et à mesure de la lecture, face à l’impossibilité de l’auteur de choisir un genre littéraire et de s’y tenir. Alors que le destin légendaire ...

  7. 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...

  8. Quand la musique donne le ton

    DEFF Research Database (Denmark)

    Reeh, Henrik

    2017-01-01

    Le lycée Sainte-Anne de Copenhague est un établissement réputé pour les résultats de ses élèves et pour être le foyer d’une intense tradition chorale et musicologique. L’article interroge les parcours de 32 élèves d’une même classe, tous reçus au baccalauréat 2014 avec une option musique et mathé...... de comprendre cette coexistence entre musique et éducation, la relation entre « individu » et « communauté » est examinée et la notion de « culture » désigne le point d’articulation qui peut rendre compte de la dynamique pédagogique en question....

  9. 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.

  10. 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?”.

  11. Le bonheur est dans les airs

    OpenAIRE

    Robène, Luc; Bodin, Dominique; Héas, Stéphane

    2010-01-01

    A partir des années 1880, en France, la dimension touristique des ascensions en ballon prend une importance croissante. En marge des pratiques strictement utilitaires de l'aérostation s’élabore un univers davantage tourné vers la communion et / ou vers le face-à-face de l'homme avec la nature en altitude. L'observation du milieu aérien, la confrontation avec la sauvagerie des éléments et le bien-être que l'environnement vierge des hauteurs est susceptible de procurer aux aéronautes constituen...

  12. Le CRDI au Népal

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

    Au cours des années 1980 et 1990, les recherches menées dans le domaine de la phytosélection ont donné lieu à l'amélio- ration du rendement de céréales telles que le mil et l'orge. Par la suite, d'autres activités de recherche ont rendu les agriculteurs mieux en mesure de préserver la diversité génétique de leurs cultures ...

  13. 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.

  14. Lele de l'énergie dans le développement rural | CRDI - Centre de ...

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

    21 oct. 2010 ... L'énergie est sans aucun doute l'un des principaux moteurs du ... de ses recherches sur l'énergie, l'environnement et le développement rural. ... Durban, Mumbai et Rio illustrent la croissance rapide et la transformation qui a ...

  15. 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.

  16. [Expression of erythroblastic leukemia viral oncogene homolog 3 (ErbB-3) binding protein-1, matrix metalloproteinases, eplthelial cadherin in adenoid cystic carcinoma and correlation analysis].

    Science.gov (United States)

    Sun, Jian; Yu, You-cheng; Luo, Yi-xi; Tian, Zhen

    2012-12-01

    To investigate the expression of ErbB-3 binding protein-1 (EBP-1), matrix metalloproteinase 9 (MMP-9) and E-cadherin (E-cad) in adenoid cystic carcinoma and their correlation. Immunohistochemistry(PV6000 method) was used to detect EBP-1, MMP-9 and E-cad expression in 66 cases of adenoid cystic carcinoma tissues and matched para-cancerous normal tissues. In this study all cases were successfully followed up. The positive expression rate of EBP-1 in adenoid cystic carcinoma tissues was 85%. EBP-1 expression was significantly correlated to pathological pattern and clinical stage (P correlation between EBP-1 and E-cad expression, and positive correlation between EBP-1 and MMP-9. EBP-1 and its correlation with MMP-9 and E-cad may be used as useful indicators for clinical assessment of tumor biological behavior and prognosis in patients with adenoid cystic carcinoma.

  17. 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.

  18. Pronto chi parla. Cesare e le intercettazioni telefoniche

    Directory of Open Access Journals (Sweden)

    Paolo Caponi

    2010-03-01

    Full Text Available Pronto chi parla. Cesare e le intercettazioni telefoniche (Ugo Guspini, L’orecchio del regime. Le intercettazioni telefoniche al tempo del fascismo, Milano, Mursia, 1973, pp. 262 di Paolo Caponi

  19. 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.

  20. Plaidoyer pour le lavage de nez dans les pathologies naso ...

    African Journals Online (AJOL)

    Le lavage de nez permet l'humidification des muqueuses partant favorise le nettoyage mucociliaire en enlevant voire diminuant les croutes favorise leur élimination et ainsi la guérison en réduisant le recours aux antibiotiques [4-10]. Sans danger, le lavage de nez est bien tolérée tant chez les enfants que chez les adultes.

  1. 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 ...

  2. 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 ...

  3. 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 ...

  4. "Le CERN restera un grand employeur"

    CERN Multimedia

    Monin, V

    2002-01-01

    "Pour le porte-parole du CERN, la suppression de 600 postes d'ici 2007 était prévue depuis bien longtemps. Il s'agit de départs en retraite qui ne sont en aucun cas liés au dépassement du budget du LHC" (1 page).

  5. Le Chatelier's Principle, Temperature Effects, and Entropy.

    Science.gov (United States)

    Campbell, J. Arthur

    1985-01-01

    One of the most useful methods of understanding chemical equilibria is provided by Le Chatelier's principle. The relationships between this principle, temperature, and entropy are discussed. Tables with thermodynamic data for some net reactions commonly used to illustrate the principle and for reactions involving gases are included. (JN)

  6. Microscopic Description of Le Chatelier's Principle

    Science.gov (United States)

    Novak, Igor

    2005-01-01

    A simple approach that "demystifies" Le Chatelier's principle (LCP) and simulates students to think about fundamental physical background behind the well-known principles is presented. The approach uses microscopic descriptors of matter like energy levels and populations and does not require any assumption about the fixed amount of substance being…

  7. Le Chatelier's principle in replicator dynamics

    Science.gov (United States)

    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.

  8. ON THE LE CHATELIER-SAMUELSON PRINCIPLE

    OpenAIRE

    ANDERSON, Richard K.; TAKAYAMA, Akira

    1992-01-01

    This paper obtains a method to derive the Le Chatelier-Samuelson Principle. Not only is it simpler and more straightforward than other methods in the literature, but also it enables us to obtain important results which are not readily accessible otherwise.

  9. Le Chatelier--Right or Wrong?

    Science.gov (United States)

    Helfferich, Friedrich G.

    1985-01-01

    Presents a class exercise designed to find out how well students understand the nature and consequences of the mass action law and Le Chatelier's principle as applied to chemical equilibria. The exercise relates to a practical situation and provides simple relations for maximizing equilibrium quantities not found in standard textbooks. (JN)

  10. Le Débat des semences

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

    Équilibrer les obligations issues de traités ...... Bien que les opinions diffèrent sur le caractère moral et la sécurité des cultures ...... Anonyme, citant William Haseltine, P.D.G. de Human Génome Sciences, Inc., Company Hopes Gène Trawl Will ...

  11. The LeChatelier-Samuelson principle revisited

    NARCIS (Netherlands)

    Dietzenbacher, E

    1992-01-01

    Within the context of a linear Leontief model, the LeChatelier-Samuelson principle examines the effects of an increase in some final demand on the output levels under the constraint that the production of certain goods is held at its original value. The principle states that the increase in any

  12. Le rêve dans la psychanalyse

    Czech Academy of Sciences Publication Activity Database

    Pechar, Jiří

    2016-01-01

    Roč. 12, č. 3 (2016), s. 1-5 ISSN 1336-6556 Institutional support: RVO:67985955 Keywords : psychoanalysis * dream-work * condensation * displacement * screen-memory * Freud Subject RIV: AA - Philosophy ; Religion http://www.ostium.sk/sk/le-r%c8%87ve-dans-la-psychanalyse/

  13. Le Shuttle, the locomotive from Eurotunnel

    OpenAIRE

    Gabriel MOISA

    2002-01-01

    This paper present some performances of locomotive ‘Le Shuttle’, so-called locomotive from ‘Eurotunnel’, techniques characteristics of traction motors 6 FHA 7079 and converters witch use it, the principal electric scheme and its function principle and no at last rind the principle scheme of command-control equipment MICAS-S2 with detailed description of its operation mode.

  14. LES MISSIONS DE PAIX ET LE CANADA

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

    Cambodge : Politique étrangère et missions de paix ...... Cette force constituerait la réserve stratégique du Conseil de sécurité, qui pourrait la ...... le recrutement se faisait par clan, les nouvelles recrues étant placées dans des unités de leurs ...

  15. LE SYSTEME ALGERIEN DE PROTECTION SOCIALE : ENTRE ...

    African Journals Online (AJOL)

    Son plan de sécurité sociale s'inscrivait dans une politique d'ensemble à dominante ..... article, le non payement des cotisations par les entreprises et les ..... la stratégie de développement17 suivie par l'Etat après l'indépendance. Mais ce ...

  16. Con la testa fra le nuvole

    Directory of Open Access Journals (Sweden)

    André Greboge

    2015-06-01

    Full Text Available Partitura de Con la testa fra le nuvole, composta em 2015 para piano e harpa de pedais. Este memorial apresenta as notas sobre a obra e a organização do processo composicional, baseada em um insight composicional a partir da ideia de complexidade apresentada por James Tenney em Meta Meta-hodos (1988.

  17. 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

  18. 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

  19. 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 ...

  20. 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.

  1. le 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...

  2. Tabagisme et dysfonction erectile chez les personnes vivant avec le ...

    African Journals Online (AJOL)

    La dysfonction erectile (DE) est un probleme de sante publique qui altere la qualite de vie des patients. Chez les personnes infectees par le VIH, le tabagisme en association ii d'autres facteurs pourrait accroitre le risque de survenue de ce trouble. L'objectif de cette etude est de determiner la prevalence de laDE, les ...

  3. 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.

  4. 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.

  5. 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 ...

  6. Publications | Page 162 | 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 ...

  7. 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

  8. 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

  9. Voir tous les projets | CRDI - Centre de recherches pour le ...

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

    causant les tumeurs) qui vise à interrompre l'expansion des cellules ayant un potentiel de malignité. Région(s): Canada, Israel, Brazil. Financement total : CA$ 669,800.00. Lele de l'IL6 dans le cancer du foie lié à l'hépatopathie métabolique.

  10. Publications | Page 173 | CRDI - Centre de recherches pour le ...

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

    E-Commerce in the Asian Context : Selected Case Studies. Le commerce électronique en Asie retient beaucoup l'attention en raison de la prolifération des connexions Internet et des technologies connexes dans la région. Face à cette tendance, le Centre de recherches pour le développement international (.

  11. Lele 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 lele des chefs traditionnels dans la gouvernance locale en Afrique. Bien qu'il soient souvent ignorés par les organismes de développement international, les ...

  12. 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 ...

  13. 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).

  14. 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.

  15. 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 ...

  16. 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.

  17. 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, ...

  18. 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 ...

  19. 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.

  20. Le devenir actif du corps affectif

    Directory of Open Access Journals (Sweden)

    Pascal Séverac

    2005-09-01

    Full Text Available Le but de cet article est de saisir ce que signifie, pour le corps, être actif. À partir de la proposition 49 de la partie IV de l’Éthique, on propose de distinguer deux manières d’appréhender le corps – soit comme corps organique, soit comme corps affectif -, et l’on montre que la question éthique du devenir actif s’adresse à la dimension affective du corps. Il faut penser le devenir actif du corps affectif comme augmentation de son aptitude non seulement à affecter, mais aussi à être affecté. En effet, être affecté pour le corps n’est pas identique à pâtir : au contraire, plus est grande l’ouverture sensible d’un corps aux autres corps, plus est grande son activité éthique.The aim of this paper is to understand how the body can be active. With the proposition 49 of the fourth part of Ethics, two ways of conceiving of the body are distinguished : like an organic body or like an affective body. The ethics question of becoming active is about the affective body. This becoming active must be understood as increasing of the ability to affect, as well as to be affected. To be affected is different from to be passive. On the contrary, the more the body is able to be affected, the more he becomes active.

  1. Gossip Girls : lele 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 lele 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.

  2. 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 ...

  3. 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 ...

  4. 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...

  5. La responsabilité de rendre compte : lele des médias dans le ...

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

    28 janv. 2011 ... Ce journaliste chevronné et professeur à l'École de journalisme et de communication de l'Université Carleton s'intéresse à l'histoire du Rwanda depuis qu'il a effectué son tout premier voyage dans ce pays africain, au milieu des années 1990. En 1996, en effet, il travaillait là-bas comme journaliste pour le ...

  6. Le Kongo de Sony Labou Tansi

    Directory of Open Access Journals (Sweden)

    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 ?

  7. 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...

  8. 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.

  9. Le Feu et ses Usages Militaires

    Directory of Open Access Journals (Sweden)

    Finó, J. F.

    1970-12-01

    Full Text Available LE feu a toujours été une arme puissante. L'homme préhistorique, les Assyriens, les Grecs, les Byzantins, les Arabes, les bombes incendiaires de notre aviation, autant d'exemples de son usage militaire dans des pays et des temps fort divers. De plus, une de ses variantes, le feu grégeois pulvérulent, a été à l'origine de la poudre à canon. Il a donc paru intéressant de rassembler quelques données à ce sujet et de rappeler briévement la production des feux de guerre, leur lancement et la défense contre ses effets. Accessoirement, de dire quelques mots sur une autre branche de la chimie de guerre: les gaz asphyxiants.

  10. 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

  11. Le travail en évolution

    OpenAIRE

    Alexandre, Marie; Attali, Michaël; Baeza, Carole; Champy-Remoussenard, Patricia; Deschenaux, Frédéric; Deville, Julie; Gonin, Audrey; Guedj-Chauchard, Muriel; Guillemot, Valérie; Hardouin, Magali; Hébrard, Pierre; Labbé, Sabrina; Maillard, Fabienne; Roussel, Chantal; Saint-Martin, Jean

    2014-01-01

    Le travail est une réalité sociale souvent perçue comme « centrale » dans l’organisation de la société et soumise à des « métamorphoses » rapides et permanentes qui se répercutent sur les pratiques éducatives. À l’heure où le chômage et les formes de précarité vont grandissant, où la demande de professionnalisation des dispositifs de formation se fait pressante, des questions complexes pour la recherche en éducation se trouvent posées. Les processus de professionnalisation, s’ils interpellent...

  12. Aiutare le vittime della mafia a ribellarsi

    Directory of Open Access Journals (Sweden)

    Roberto Riccardi

    2007-09-01

    Full Text Available Nino Miceli is a Sicilian man, owner of a small business: at the beginning of 1990s he is concessionnaire of cars in Gela, an quite big town in Sicily. He works hard and soon he starts to earn a lot. Business is very good, and customers are satisfied and everything seems to go on successfully. But the mafia keeps an eye on him and, at a certain point, he was asked to pay them what in Italy is called “pizzo”. Nino Miceli does not want to pay it, he does not want to surrender to the mafia coercion. However, at the beginning he pays the “pizzo” but then he starts to record the conversation he has with those men (the “mafiosi”, in order to prove and demonstrate the crime. He also looks for protection at the local station of Carabinieri; finally, he decides to report the extortion but, from that time on, he starts to experience more and more serious threats.Helped by an officer of Carabinieri, he becomes a witness of justice and, for that reason, he must change his identity. He leaves Sicily along with his family and move into a different region of Italy, far from his town, where nobody knows him. In 2007 he decides to write a book of memories, titled “Io, il fu Nino Miceli” (in English it could sound like “I was Nino Miceli”. This article tells his story, speaking also about the role played by the Arma of Carabinieri in supporting victims of racket and usury.Nino Miceli est un entrepreneur sicilien originaire de Realmonte, une ville en province d'Agrigento. Au début des années 90, il est proprietaire du garage Lancia à Gela. Il s'engage beaucoup dans son travail et les résultats ne tardent pas à arriver. La clientèle augmente, les affaires vont bon train, mais c'est justement quand l'entreprise est en train de prospérer que la mafia lui demande des comptes. Il doit payer le pot-de-vin comme tous les commerçants du quartier. Nino Miceli n'est pas d'accord avec cela. Au début il subit, mais il commence bientôt

  13. Mel Gibson contre le boulevard Raspail

    Directory of Open Access Journals (Sweden)

    Boris Jeanne

    2007-03-01

    Full Text Available Que peuvent faire les historiens et les anthropologues spécialistes de l’Amérique face à la puissance médiatique et commerciale d’Apocalypto, le dernier film de Mel Gibson, produit par Buena Vista (c'est-à-dire Disney et ayant déjà engrangé plus de 50 millions de dollars de recette avant même sa sortie en France ? Le cinéma est un art du présent, et quelle que soit l’exactitude de la reconstitution historique qu’il prétend parfois présenter, il demeure un puissant vecteur d’analyse de la soc...

  14. Le Japon quatre fois frappé

    Directory of Open Access Journals (Sweden)

    Philippe Pelletier

    2011-03-01

    Full Text Available Illustration 1 – Hauteur du tsunami sur le littoral (en mètresSources : Brunet R. (dir, 1994. Géographie universelle. Belin/Reclus ;Pelletier Ph., Fournier C., 2008. Atlas du Japon. Autrement ; http://silatitudes.teledetection.fr/index.php :actualité/54-mapping-japan-earthquake-and-tsunami Dans un essai polémiste au destin retentissant, du moins auprès de ceux qui s’intéressent sérieusement à l’Asie orientale, le sinologue Jean François Billeter dénonçait l’approche néo-orientaliste du sino...

  15. 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.

  16. 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...

  17. Le point sur l'initiative NEHSI

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

    soient affectées de manière à avoir des effets tangibles. Elle a pour but de faire en sorte que les planificateurs .... à bien, et on en a fait la démonstration aux autorités. Mesure de la malnutrition dans le cadre de l'audit social ... infantile, y compris des médicaments, et l'amélioration du fonctionnement de ces établissements;.

  18. Les hybridations interspecifiques dans le genre Phaseolus ...

    African Journals Online (AJOL)

    La réussite de l'introgression de caractères utiles chez le haricot commun P. vulgaris à partir des deux espèces P. coccineus et P. polyanthus dépend en partie des génotypes utilisés. Ce travail vise à identifier des génotypes de Phaseolus compatibles lors des hybridations interspécifiques et à identifier les hybrides issus ...

  19. The Le Chatelier Principle in lattices

    OpenAIRE

    Julian Jamison

    2006-01-01

    The standard Le Chatelier Principle states that the long-run demand for a good (in which by definition there are fewer restraints on the variables) is more elastic than short-run demand. The fundamental insight above goes well beyond demand theory, and proofs of this basic idea have been found in various settings. Nearly all of these have been continuous optimization problems requiring assumptions on the continuity of the objective function and on the convexity of the choice set. However, the...

  20. Le Shuttle, the locomotive from Eurotunnel

    Directory of Open Access Journals (Sweden)

    Gabriel MOISA

    2002-12-01

    Full Text Available This paper present some performances of locomotive ‘Le Shuttle’, so-called locomotive from ‘Eurotunnel’, techniques characteristics of traction motors 6 FHA 7079 and converters witch use it, the principal electric scheme and its function principle and no at last rind the principle scheme of command-control equipment MICAS-S2 with detailed description of its operation mode.

  1. LE SECTEUR INFORMEL EN ALGERIE : APPROCHES, ACTEURS ...

    African Journals Online (AJOL)

    Résumé. Le secteur informel en Algérie est peu étudié de manière directe et .... très diverses que Bernard (1980,1988) a classées en 3 catégories plus ou moins .... sont amenés en raison de l'ambiguïté de la loi et de sa faible appli- cation à ...

  2. LE DÉVELOPPEMENT DÉMOCRATIQUE

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

    Il en est ainsi parce que les normes et les idéaux qui stimulent la recherche scientifique sont également au coeur de la ... les fondements de toute saine démocratie. De même, certaines des recherches appliquées qu'appuie le CRDI peuvent con- .... criminalité et de la violence. En outre, une fois choisi leur propre mode de.

  3. Un incidentalome surrenalien inhabituel: le ganglioneurome

    African Journals Online (AJOL)

    S. Attafi

    Résumé. Le ganglioneurome est une tumeur neurogène bénigne, rare, qui se développe à partir des cellules gan- glionnaires sympathiques. Elle se localise essentiellement dans la région rétropéritonéale. La localisation surrénalienne est rare. Nous rapportons un cas de ganglioneurome surrénalien chez une femme ...

  4. Focus : Le torrent de Faucon (Ubaye

    Directory of Open Access Journals (Sweden)

    Frédéric Liébault, Christophe Peteuil et Alexandre Remaître

    2010-09-01

    Full Text Available Le torrent du Faucon, dans la vallée de l'Ubaye, est connu pour ses nombreux phénomènes torrentiels. Les auteurs nous présentent ici l’étude du bilan sédimentaire du torrent du Faucon à travers l’exemple de la lave torrentielle du 5 août 2003.

  5. Le Chien de faïence

    Directory of Open Access Journals (Sweden)

    Marie-Laure Schultze

    2011-11-01

    Full Text Available Marie-Laure Schultze est enseignante-chercheure depuis une vingtaine d'années. Elle a travaillé en Angleterre, au Canada et surtout en France, où elle est actuellement en poste à Aix-Marseille Université. Elle y a ouvert avec une collègue des ateliers (exceptionnellement rares dans les universités françaises de traduction créatrice et d’écriture plurilingue ; ces ateliers sont destinés à leurs étudiants apprenant l’anglais et consolidant le français. En parallèle, et dans les interstices laissés par sa recherche sur la place de l’écriture créatrice dans l’apprentissage des langues et sa famille (un compagnon et trois enfants constituent le noyau de la drupe, elle écrit et publie bon an mal an cahin caha ses textes (de la fiction courte, du théâtre, deux romans en chantier, des histoires pour enfants... sur son blog http://carnetdetextes.wordpress.com/

  6. Dictionnaire Le Robert et Collins anglais senior

    CERN Document Server

    2016-01-01

    Le plus complet et le plus actuel des grands dictionnaires bilingues anglais : près d'1 million de mots, expressions et traductions ; 2 dictionnaires de synonymes (un pour chaque langue) ; un dictionnaire business de 15 000 termes. La référence pour les ensiengnants et les traducteurs Une richesse inégalée de sens et de nuances : plus de 950 000 mots, expressions et traductions des milliers d'exemples tirés de la presse et de la littérature le vocabulaire terminologique : sciences, économie, nouvelles technologies,... tous les niveaux de langue : littéraire, familier, argotique... Une langue mise à jour et actuelle : des milliers de traductions nouvelles : zero-hour contract, sunset clause, culture fund... Une dimension internationale l'anglais britannique, américain, écossais, irlandais, australien... Les références culturelles anglo-saxonnes : institutions, traditions, événements, personnages importants, phrases célèbres de la littérature, du cinéma... Des aides pointues : 800 notes su...

  7. Thermo-pneumatic canning; Le gainage thermopneumatique

    Energy Technology Data Exchange (ETDEWEB)

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

    1958-07-01

    In the thermo-pneumatic canning, the fuel is enclosed in its can with a clearance that must be reduced by external heated gas pressure. The principal applications are: a) binding magnesium cans on to uranium in fuel elements of reactors cooled by CO{sub 2} under pressure, b) application of a can to a hollow bar of uranium too thin to resist the pressure of cold hydraulic canning, c) application of an aluminium can to a bar, with an initial diametrical clearance between uranium and can too great to sustain cold hydraulic canning without buckling, d) detection of major leakage in the slugs. (author) [French] Ce procede consiste a appliquer une gaine sur une barre d'uranium par pression hydrostatique d'un gaz chaud. Les principales applications sont: a) le frettage des gaines de magnesium des elements combustibles des piles refroidies au CO{sub 2} sous pression, b) le gainage d'un barreau creux qui serait ecrase a froid, c) le gainage avec un jeu initial trop fort pour etre effectue a froid sans plisser, d) la detection des fuites de cartouches. (auteur)

  8. 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.

  9. 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...

  10. 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...

  11. 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

  12. 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 ...

  13. The EGFR/ErbB3 Pathway Acts as a Compensatory Survival Mechanism upon c-Met Inhibition in Human c-Met+ Hepatocellular Carcinoma.

    Directory of Open Access Journals (Sweden)

    Steven N Steinway

    Full Text Available c-Met, a high-affinity receptor for Hepatocyte Growth Factor (HGF, plays a critical role in tumor growth, invasion, and metastasis. Hepatocellular carcinoma (HCC patients with activated HGF/c-Met signaling have a significantly worse prognosis. Targeted therapies using c-Met tyrosine kinase inhibitors are currently in clinical trials for HCC, although receptor tyrosine kinase inhibition in other cancers has demonstrated early success. Unfortunately, therapeutic effect is frequently not durable due to acquired resistance.We utilized the human MHCC97-H c-Met positive (c-Met+ HCC cell line to explore the compensatory survival mechanisms that are acquired after c-Met inhibition. MHCC97-H cells with stable c-Met knockdown (MHCC97-H c-Met KD cells were generated using a c-Met shRNA vector with puromycin selection and stably transfected scrambled shRNA as a control. Gene expression profiling was conducted, and protein expression was analyzed to characterize MHCC97-H cells after blockade of the c-Met oncogene. A high-throughput siRNA screen was performed to find putative compensatory survival proteins, which could drive HCC growth in the absence of c-Met. Findings from this screen were validated through subsequent analyses.We have previously demonstrated that treatment of MHCC97-H cells with a c-Met inhibitor, PHA665752, results in stasis of tumor growth in vivo. MHCC97-H c-Met KD cells demonstrate slower growth kinetics, similar to c-Met inhibitor treated tumors. Using gene expression profiling and siRNA screening against 873 kinases and phosphatases, we identified ErbB3 and TGF-α as compensatory survival factors that are upregulated after c-Met inhibition. Suppressing these factors in c-Met KD MHCC97-H cells suppresses tumor growth in vitro. In addition, we found that the PI3K/Akt signaling pathway serves as a negative feedback signal responsible for the ErbB3 upregulation after c-Met inhibition. Furthermore, in vitro studies demonstrate that

  14. 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 ...

  15. 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 ...

  16. 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.

  17. 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...

  18. 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 ...

  19. 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 ...

  20. 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...

  1. 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 ...

  2. 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..

  3. Publications | Page 14 | CRDI - Centre de recherches pour le ...

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

    Le livre 2016 Ciudades de Vida y Muerte: La ville et le pacte social pour la contention de la violence présente une analyse convaincante de la coexistence de la violence et de la corruption Avec compassion et solidarité dans les villes du Venezuela - et les leçons qui peuvent être tirées de leur expérience. Cities of Life and ...

  4. LE CARCINOME ONCOCYTAIRE DE LA PAROTIDE : A PROPOS D ...

    African Journals Online (AJOL)

    Après chirurgie, les récidives sont fréquentes. Lele de la radio- thérapie et de chimiothérapie est toujours controversé.Le pronostic est mauvais. Mots clés : Carcinome oncocytaire, parotide, chirurgie, radiothérapie. SUMMARY. Introduction : Oncocyticcarcinomais a rare salivary gland tumor. its management is not codified ...

  5. Publications | Page 64 | CRDI - Centre de recherches pour le ...

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

    Un projet financé par le CRDI a contribué à abolir les barrières entre la pratique de la recherche-action participative et la formation et la pensée universitaires sur le terrain. Le projet a aussi encouragé des intervenants du Sud à exercer un leadership au regard de communautés régionales et thématiques de praticiens se ...

  6. Publications | Page 65 | CRDI - Centre de recherches pour le ...

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

    Un projet financé par le CRDI a contribué à abolir les barrières entre la pratique de la recherche-action participative et la formation et la pensée universitaires sur le terrain. Le projet a aussi encouragé des intervenants du Sud à exercer un leadership au regard de communautés régionales et thématiques de praticiens se ...

  7. Une nouvelle ouverture sur le monde pour les femmes | CRDI ...

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

    'appellent ailleurs dans le dédale d'étals et d'allées serrés. En plus de son travail sur le marché, Jertrudes est également secrétaire de l'association des femmes qui vendent sur ce marché. Le groupe est un endroit où elles ...

  8. Publications | Page 154 | CRDI - Centre de recherches pour le ...

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

    Armer les villes contre la faim : Systèmes alimentaires urbains durables. Le XXe siècle a été le témoin d'une croissance massive des populations urbaines. En 1990, le tiers des habitants de la planète vivaient dans des villes de plus d'un million d'habitants. En outre, la faim et la malnutrition.

  9. Publications | Page 10 | CRDI - Centre de recherches pour le ...

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

    L'obésité est un facteur de risque de plusieurs maladies non transmissibles, dont les cardiopathies, l'hypertension, le diabète et le cancer. Conflit et développement dans les collines de Guwahati. Dans la ville de Guwahati, dans le nord-est de l'Inde, la croissance rapide a alimenté une explosion de développement non ...

  10. Centre de recherches pour le développement international ...

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

    André Lavoie

    Centre de recherches pour le développement international. Règlement institutionnel. Approuvé par le Comité exécutif de la haute direction. - 1 -. Version 3.0.0 en vigueur le 15-10-2015. Conférences et événements. 1. Contexte. 2. Objectif. 3. Application. 4. Définitions. 5. Rôles et responsabilités. 5.1. Employés. 5.2.

  11. Publications | Page 122 | 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 ... par le CRDI qui fournit des ordinateurs aux écoles tout en créant des emplois permet de s'attaquer au problème environnemental causé par les déchets électroniques en ...

  12. Publications | Page 179 | CRDI - Centre de recherches pour le ...

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

    Lele de l'énergie dans le développement rural. Hisham Zerriffi n'a aucun mal à énumérer les bienfaits de l'électrification des zones rurales : une meilleure éducation, puisque les enfants ont de la lumière pour lire et étudier, de meilleurs établissements de santé, de meilleurs.

  13. Publications | Page 177 | CRDI - Centre de recherches pour le ...

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

    Lele de l'énergie dans le développement rural. Hisham Zerriffi n'a aucun mal à énumérer les bienfaits de l'électrification des zones rurales : une meilleure éducation, puisque les enfants ont de la lumière pour lire et étudier, de meilleurs établissements de santé, de meilleurs.

  14. Publications | Page 19 | CRDI - Centre de recherches pour le ...

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

    Le documentaire Forward Home, qui a été produit dans le cadre du projet Avantages découlant de la circulation des cerveaux des pays de la CARICOM ainsi que du tourisme et des investissements de la part de la diaspora caribéenne du CRDI, révèle la puissance économique de la diaspora caribéenne. De la ferme à la ...

  15. La prolusione di rocco e le dottrine del processo penale

    OpenAIRE

    Renzo Orlandi

    2015-01-01

    L’articolo analizza le conseguenze del pensiero giuridico di Arturo Rocco, dal 1910 nella dottrina di procedura penale, ossia, il metodo tecnico-giuridico (esegesi, sistematica e critica). La dogmatica di procedura pena- le inizia con la monografia di Giovanni Conso, nel 1955. L’insoddisfazione con il tecnicismo giuridico e con la mancanza di maturità scientifica si è manifestata con Carnelutti nel 1946 (Cerenterola), sottolineando le peculiarità strutturali del procedimento penale. In questa...

  16. Concepteur Web | CRDI - Centre de recherches pour le ...

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

    Gérer l'ensemble du cycle de conception, y compris l'architecture technique, le plan du site, l'interface de l'utilisateur, la conception de la base de données, toute la programmation et la documentation. Effectuer l'évaluation des besoins, la création de prototypes, la conception, le codage, les essais et le débogage. Définir et ...

  17. Publications | Page 94 | 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, ... Le syndrome... Diamants de guerre — pour en finir. L'important accord international sur les diamants conclu cette année ne portera pas fruits s'il n'est pas ...

  18. Tanzanie | Page 18 | CRDI - Centre de recherches pour le ...

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

    Read more about Fermented food for life (CIFSRF Phase 2). Langue English. Read more about Mobilisation au service de la préservation. Langue French. Read more about Lele des universités africaines dans l'innovation au service du développement inclusif. Langue French. Read more about L'emploi dans le secteur ...

  19. 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

    Directory of Open Access Journals (Sweden)

    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

  20. 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.

  1. Le paysage anglais: du jardin à la campagne

    Directory of Open Access Journals (Sweden)

    Gilly LEHMANN

    1987-12-01

    Full Text Available Lele 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.

  2. Chili : tous les projets | CRDI - Centre de recherches pour le ...

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

    Région: Chile, Colombia, Mexico. Programme: Agriculture et sécurité alimentaire. Financement total : CA$ 5,230,900.00. Lele du secteur privé dans la réduction de la corruption en Amérique latine. Projet. Dans le cadre de ce projet, on étudiera les efforts déployés par le secteur privé pour améliorer la conformité aux lois ...

  3. Thermal Orbital Environmental Parameter Study on the Propulsive Small Expendable Deployer System (ProSEDS) Using Earth Radiation Budget Experiment (ERBE) Data

    Science.gov (United States)

    Sharp, John R.; McConnaughey, Paul K. (Technical Monitor)

    2002-01-01

    The natural thermal environmental parameters used on the Space Station Program (SSP 30425) were generated by the Space Environmental Effects Branch at NASA's Marshall Space Flight Center (MSFC) utilizing extensive data from the Earth Radiation Budget Experiment (ERBE), a series of satellites which measured low earth orbit (LEO) albedo and outgoing long-wave radiation. Later, this temporal data was presented as a function of averaging times and orbital inclination for use by thermal engineers in NASA Technical Memorandum TM 4527. The data was not presented in a fashion readily usable by thermal engineering modeling tools and required knowledge of the thermal time constants and infrared versus solar spectrum sensitivity of the hardware being analyzed to be used properly. Another TM was recently issued as a guideline for utilizing these environments (NASA/TM-2001-211221) with more insight into the utilization by thermal analysts. This paper gives a top-level overview of the environmental parameters presented in the TM and a study of the effects of implementing these environments on an ongoing MSFC project, the Propulsive Small Expendable Deployer System (ProSEDS), compared to conventional orbital parameters that had been historically used.

  4. Combined use of anti-ErbB monoclonal antibodies and erlotinib enhances antibody-dependent cellular cytotoxicity of wild-type erlotinib-sensitive NSCLC cell lines

    Directory of Open Access Journals (Sweden)

    Cavazzoni Andrea

    2012-12-01

    Full Text Available Abstract Background The epidermal growth factor receptor (EGFR is an established target for anti-cancer treatment in different tumour types. Two different strategies have been explored to inhibit this pivotal molecule in epithelial cancer development: small molecules TKIs and monoclonal antibodies. ErbB/HER-targeting by monoclonal antibodies such as cetuximab and trastuzumab or tyrosine-kinase inhibitors as gefitinib or erlotinib has been proven effective in the treatment of advanced NSCLC. Results In this study we explored the potential of combining either erlotinib with cetuximab or trastuzumab to improve the efficacy of EGFR targeted therapy in EGFR wild-type NSCLC cell lines. Erlotinib treatment was observed to increase EGFR and/or HER2 expression at the plasma membrane level only in NSCLC cell lines sensitive to the drug inducing protein stabilization. The combined treatment had marginal effect on cell proliferation but markedly increased antibody-dependent, NK mediated, cytotoxicity in vitro. Moreover, in the Calu-3 xenograft model, the combination significantly inhibited tumour growth when compared with erlotinib and cetuximab alone. Conclusion Our results indicate that erlotinib increases surface expression of EGFR and/or HER2 only in EGFR-TKI sensitive NSCLC cell lines and, in turns, leads to increased susceptibility to ADCC both in vitro and in a xenograft models. The combination of erlotinib with monoclonal antibodies represents a potential strategy to improve the treatment of wild-type EGFR NSCLC patients sensitive to erlotinib.

  5. Stable RNA interference of ErbB-2 gene synergistic with epirubicin suppresses breast cancer growth in vitro and in vivo

    International Nuclear Information System (INIS)

    Hu Xiaoqu; Su Fengxi; Qin Li; Jia Weijuan; Gong Chang; Yu Fengyan; Guo Jujiang; Song Erwei

    2006-01-01

    Overexpression of human epidermal growth factor receptor-2 (Her2, ErbB-2) contributes to the progression and metastasis of breast cancer, implying that Her2 gene is a suitable target of RNA interference (RNAi) for breast cancer therapy. Here, we employed plasmid-mediated expression of 2 different Her2-shRNAs (pU6-Her2shRNAs) efficiently silenced the target gene expression on Her2 expressing SKBR-3 breast cancer cells in both mRNA and protein levels. Consequently, pU6-Her2shRNA increased apoptosis and reduced proliferation of SKBR-3 cells assayed by TUNEL and MTT, respectively. In vivo, intra-tumor injection of pU6-Her2shRNA inhibited the growth of SKBR-3 tumors inoculated subcutaneously in nude mice. Furthermore, pU6-Her2shRNA synergized the tumor suppression effect of epirubicin to SKBR-3 cells in vitro and implanted subcutaneously in nude mice. Therefore, we concluded that stable silencing of Her2 gene expression with plasmid expressing shRNA may hold great promise as a novel therapy for Her2 expressing breast cancers alone or in combination with anthracycline chemotherapy

  6. Le Chatelier's principle with multiple relaxation channels

    Science.gov (United States)

    Gilmore, R.; Levine, R. D.

    1986-05-01

    Le Chatelier's principle is discussed within the constrained variational approach to thermodynamics. The formulation is general enough to encompass systems not in thermal (or chemical) equilibrium. Particular attention is given to systems with multiple constraints which can be relaxed. The moderation of the initial perturbation increases as additional constraints are removed. This result is studied in particular when the (coupled) relaxation channels have widely different time scales. A series of inequalities is derived which describes the successive moderation as each successive relaxation channel opens up. These inequalities are interpreted within the metric-geometry representation of thermodynamics.

  7. Il corpo, lo sport, le immagini

    Directory of Open Access Journals (Sweden)

    Nicola Porro

    2009-07-01

    Full Text Available E’ stato per primo Norbert Elias, nella sua critica al riduzionismo sociologico, a lamentare la difficoltà delle scienze sociali a misurarsi con le problematiche dello sport, così come delle emozioni, della sessualità, del gioco e della guerra. Attività umane che convergono in quell’autentico luogo sociale che è il corpo. Nel caso che ci interessa, si tratta di connettere il corpo, nella sua dimensione biologica, psichica e sociale, con quell’aspetto cruciale della civilizzazione che Elias definisce sportivizzazione.

  8. Images du Mage, images pour le Mage

    Directory of Open Access Journals (Sweden)

    Daniel GREGORIO

    2007-01-01

    Full Text Available Les œuvres d’Alphonse X proposent diverses représentations du mage, qui en font, tour à tour, l’ennemi ou l’allié de la religion chrétienne. Il est vrai que parfois, comme le montre l’histoire de Simon le magicien, la pratique de la magie implique un commerce direct et néfaste avec les forces infernales. Néanmoins, les personnages de Merlin et des Rois Mages, tels qu’ils sont présentés par Alphonse X, démontrent que magie et religion peuvent cohabiter, à condition toutefois que le mage croit en la virginité de Marie et en l’Incarnation et que sa pratique magique soit bénéfique pour la communauté. Ce bénéfice requiert parfois la reconstruction de l’univers quotidien ; pour ce faire, le magicien doit savoir quand et comment utiliser des objets et des pentacles, qui lui permettront de soumettre les forces surnaturelles. Il doit donc posséder une connaissance approfondie du monde naturel et des esprits qui, conjuguée à sa foi religieuse, l’empêchera de tomber dans la démonolâtrie.Las obras alfonsíes proponen diversas aproximaciones al personaje del mago, generalmente considerado como un ser antagónico del hombre religioso. Es cierto que en algunas ocasiones, como ocurre con Simón el mago, la práctica de las artes mágicas significa un trato directo y nefasto con las fuerzas infernales. Sin embargo, personajes como Merlín o los Reyes Magos, tal y como los describe Alfonso X, subrayan una posible cohabitación entre magia y religión sin que la práctica de la una signifique la exclusión de la otra. Sólo hay que cumplir con dos condiciones : creer en la virginidad de María y que Dios se hizo hombre, y proporcionar a la comunidad un beneficio claro. Este beneficio requiere en ocasiones remodelar lo cotidiano, utilizando objetos y pentáculos, en circunstancias extremadamente determinadas, lo que implica un conocimiento exhaustivo tanto del mundo natural como del simbólico y de los espíritus. Es este

  9. Il rifiuto / Le refus / The refusal

    Directory of Open Access Journals (Sweden)

    Dominici M. R.

    2010-12-01

    Full Text Available L’articolo parte dalla problematica legata alla complessità dei flussi migratori, che vengono esaminati da diversi punti di vista: da un lato, viene evidenziato il tentativo di sottrarsi, da parte di molte persone, a situazioni ambientali di difficoltà, di sofferenza e di miseria ; dall’altro lato, si sottolinea come tale fenomeno possa essere collegato strettamente alla criminalità transnazionale.In entrambe le prospettive, si generano situazioni e rischi di vittimizzazione.Successivamente, prendendo a prestito vecchie favole, vi si costruiscono attorno le esperienze di situazioni reali che riguardano un bambino, il senso e la perdità di identità.Cet article aborde le problème de la complexité des flux migratoires. Ces derniers sont observés selon différents points de vue : d’une part, l’auter met en évidence que de nombreuses personnes essaient d’échapper à des situations éprouvantes, de souffrance et de misère ; d’autre part, l’auter souligne que ce phénomène peut être strictement lié à la criminalité transnationale.Dans les deux cas, des risques de victimisation se créent.Ensuite, en empruntant de vieilles fables, l’auter construit autour d’elles les expériences de vie réelle qui incluent un enfant, le sens et la perte d’identité. This article discusses the problem related to the complexity of migration from different points of view : on the one hand, the author underlines that a large number of people seeks to escape from difficult situations of poverty ; on the other hand, the author highlights that this phenomenon can be strictly related to transnational crime. In both cases, these situations increase the risks of victimization. Then, borrowing old fables, the author builds around them some experiences of real life including the ones of a child and of the sense and the loss of identity.

  10. L'astronomie dans le monde

    OpenAIRE

    Manfroid, Jean

    2004-01-01

    Cassini; Distance des Pléiades; Gaz très chaud au centre de notre Galaxie; FUSE; Peser une étoile froide; Masse d'une étoile; Naines brunes; Sursaut gamma dans la Galaxie; Trou noir record; Masse des neutrinos; Un satellite de notre Galaxie; Une jumelle de notre Galaxie; Vie sur Mars?; Rencontre intergalactique; Hawking change d'avis; Pollution lumineuse; Sursauts gamma; Le système solaire, une exception?; Babar et l'antimatière; Spicules; Tau Ceti; Anneau de poussières; Naissance d'une étoil...

  11. Le vespe qualunquiste e la satira politica

    Directory of Open Access Journals (Sweden)

    Maurizio Cocco

    2012-10-01

    Full Text Available The weekly review «L’Uomo Qualunque» was the most popular newspaper in Italy in the second postwar. Created by a Neapolitan playwright, Guglielmo Giannini, it was the voice of the discontent of the middle classes and strongly opposed the CLN governments and the antifascist political parties.The paper aims to provide analysis of the use of satire in the newspaper. It focuses on the section named «Le vespe», in which Giannini used jokes and humorous anecdotes to criticize the transition from fascism to democracy; in particular the epuration, the political system and its personnel.

  12. Le Verrier magnificent and detestable astronomer

    CERN Document Server

    Lequeux, James

    2013-01-01

    Le Verrier was a superb scientist. His discovery of Neptune in 1846 made him the most famous astronomer of his time. He produced a complete theory of the motions of the planets which served as a basis for planetary ephemeris for a full century. Doing this, he discovered an anomaly in the motion of Mercury which later became the first proof of General Relativity. He also founded European meteorology. However his arrogance and bad temper created many enemies, and he was even fired from his position of Director of the Paris Observatory.

  13. Le zapping, les ethnologues, et leurs Indiens

    Directory of Open Access Journals (Sweden)

    Frédérique Langue

    2005-06-01

    Full Text Available Comme toujours s'agissant des expositions mises en scène au Grand Palais, la présentation est parfaite, impeccable. La mise en valeur des objets venus aussi bien de musées brésiliens qu'européens, et les commentaires qui les accompagnent, orientent le visiteur dans un labyrinthe "exotique" de poteries et d'objets de plume, coupé de temps à autre de documentaires portant sur les rituels amérindiens, chants psalmodiques à l'appui. L'auditoire y semble comme vissé sur place, davantage d'ailleur...

  14. Books reconsidered: Emile Durkheim, Le Suicide.

    Science.gov (United States)

    Robertson, Michael

    2006-12-01

    To reappraise Emile Durkheim's taxonomy of suicide in Le Suicide in the light of recent experience. While Durkheim's scientific method and argument are fundamentally flawed, some of his concepts have instrumental value in attempting to understand the complex origins of suicidal behaviour. Durkheim's baseless dismissal of mental illness as a key determinant of suicidal behaviour weakens his thesis significantly. However, his conceptualization of anomic, egoistic and altruistic suicide provides a means of comprehending recent trends in suicidal behaviour in the former Soviet states and a possible window into the psyche of the suicides of religious and political extremists.

  15. 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 lele de chef de guerre. Deve...

  16. Fonds d'innovation pour le développement (FID) aux fins de la ...

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

    innovation en santé dans le but d'améliorer les conditions de vie des pauvres dans le monde entier. Le Fonds d'innovation pour le développement (FID) appuiera des scientifiques et des établissements voués à la recherche en santé par le ...

  17. All rates are effective 15 October 2017 / En vigueur le 15 octobre ...

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

    15 oct. 2017 ... 324. POLAND / POLOGNE. Everywhere / Dans tout le pays. 363. PORTUGAL. Everywhere / Dans tout le pays. 457. PUERTO RICO / ÉTAT LIBRE DE PORTO RICO. Everywhere / Dans tout le pays. 366. QATAR. Everywhere / Dans tout le pays. 590. ROMANIA / ROUMANIE. Everywhere / Dans tout le pays.

  18. Kierkegaard - le Philosophe, le Juge et le Droit (Kierkegaard – the Philosopher, the Judge and the Law

    Directory of Open Access Journals (Sweden)

    Ditlev Tamm

    2014-12-01

    Full Text Available Le fameux théologien et philosophe Søren Kierkegaard (1813-1855 dans son oeuvre souvnt utilize expressions et metaphors pris du monde judiciare. Il pare, quíl est bien au courant quant´au monde des jurists de son age et place. La plupart des expressions sont pris du droit penal et de la procédure pénale. Le criminel comme individu ou l’objet de línterrogation et comme coupable es tun des ses images favorites. Dans ses oeuvres Ou-bien … Ou bien et Etapes su la chemin de la vie nous encontrons un juge danois avec la possibilité de suivre ses reflections sur son travail et l’éthique d’un repésentant de la justice locale. Le juge est une des masques sous lesquelles Kierkegaard s’adresse a nous. Les oeuvres de Kierkegaard et l’utilisation des expressions prises du monde du droit sont ici présentées dans un contexte contemporaire du doit et vie á Copenhague dans les années entre 1840 et 1855 en contrastant les différances entre le narrative de Kierkegaard selon lequel le doit peut server comme example et sur l’autre côté son concept transcendental de l’être coupable. The famous Danish theologian and existentialist philosopher Søren Kierkegaard (1813-1855 in his work often used expressions or metaphors taken from judicial life, which reveals him as familiar with the legal world of his time and place. Most expressions are taken from penal law and penal procedure. The criminal as individual or the object of interrogation and guilt is one of his favorite images. In his Enten-Eller (Either/or and Stadier paa Livets Vej (Stages on Life’s Way we even meet a Danish judge and follow his reflections on his work and the ethics of a representative of local Justice. The judge is one of the masks under which Kierkegaard presents his thinking. Kierkegaard’s works and his use of expressions taken from the legal world are presented in the contemporary context of law and life in Copenhagen in the 1840ies however contrasting the

  19. 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.

  20. Le temps des cités-jardins | CRDI - Centre de recherches pour le ...

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

    gardiste conduite par le CRDI , plusieurs villes du Sud en sont venues à remettre en question l'attitude de leur administration à l'égard de l'agriculture urbaine. Ravitaillement des villes. Site de l'Organisation des Nations Unies ...