401 research outputs found
Stephane Mallarme: A synthesis of romanticism and parnassianism, 1970
No full textThe purpose of this paper is to analyse works of Stephane Mallarme, father of Symbolism, pointing out romantic and parnassian elements. Symbolism, like Romanticism, attempted to express the interior thoughts of man. The symbolist movement then, was not only a revolt against Parnassianism but also a return to Romanticism. On the other hand, one would not be incorrect in saying that Romanticism reached its culmination in the works of the symbolists poets. For this reason, an attempt will be made to show that the works of Mallarme, father of Symbolism, can be considered as a synthesis of Romanticism and Parnassianism. This thesis contains three chapters. The first chapter is devoted to a discussion of Romanticism and of Parnassianism. Special attention is given to the origin, development, characteristics and influences of each school. The relationship of one School with the other is also pointed out. The second chapter consists of a biographical sketch of Stephane Mallarme. Special emphasis is placed on factors and events in his life which may have influenced or determined the elements of Romanticism and Parnassianism in his poetry. The third chapter is devoted to an analysis of some of the poems of Stephane Mallarme", "Les Fenetres," V Apparition," "L'Azur," "Toast Funebre," "Le Vierge," "L'Apres-Midi d'un Faune." In these analyses special attention is given to the romantic and parnassian tendencies of the poems. Since these romantic-parnaassian elements occur frequently throughout his works, it has been concluded that Mallarme's poetry can be considered as a synthesis of the two poetic schools
Obama's visit to Korea : an unwavering US-ROC alliance amidst regional tensions
No full textFor more about the East-West Center, see http://www.eastwestcenter.org/Stephane Mot, Independent Author and Blogger living in Seoul, explains that "Obama's visit did not change the opinion of the vast majority of South Koreans who consider the US-ROK alliance to be unequal, but it did further confirm the importance of South Korea for US engagement towards Asia.
Characterization of a major neutralizing epitope on the yellow fever virus envelope protein using human recombinant monoclonal antibody fragments generated by phage display
No full textYellow fever virus (YFV) is a mosquito-transmitted, enveloped, positive stranded RNA virus belonging to the genus flavivirus, which causes hemorrhagic fever in humans in Africa and South America. The YFV is responsible for 200 000 clinical infections per year including 40 000 deaths. Despite the presence of a highly effective YF vaccine called 17D vaccine, this disease is now strongly re-emerging and has to be considered as a public health problem. The present live attenuated 17D vaccine has two major drawbacks: 1) the ancient production method by inoculating viable embryonated eggs which limits the vaccine production capacity and, therefore, impairs attempts to control the disease and may contribute to vaccine supply shortage. 2) this vaccine is a non clonal vaccine which is constituted of heterogenous virion sub-populations. Furthermore, recent reports of several cases of viscerotropic and neurotropic disease associated with 17D vaccination have raised the obvious question of vaccine safety. Taken together, these data show that it appears essential to design a new clonal vaccine which could be based on infectious cDNA clone and produced in animal cell culture. For this purpose, the knowledge of YFV neutralizing epitopes is essential. Because YFV immunity is mainly antibody-mediated, we wanted to isolate human neutralizing antibodies specific for YFV and use them as a tool to characterize the neutralizing epitopes of YFV. The phage display technology provides one of the most convenient systems to isolate such neutralizing recombinant antibody fragments. We generated YF patient-derived antibody phage libraries which were screened against purified virions of the YFV-204-WHO vaccine strain. This step led to the isolation of several single-chain antibody fragments (scFv) which recognized conformational and pH sensitive epitopes in the envelope E protein. Three genetically closely-related and competing scFvs were found to be able to neutralize in vitro the 17D vaccine strain and five wild-type African strains of YFV. To map their epitopes, neutralization escape variants of the YFV-17D-204-WHO were generated using one high-affinity scFv (scFv-7A). Amino acids (aa) E-153, E-154 and E-155 in domain I and aa E-71 in domain II of the E protein were shown to be the critical components of one complex neutralizing epitope. These aa do not form a contiguous epitope on the monomeric E protein, but are in close vicinity in the dimeric form the E protein is predicted to adopt, based on the crystal structures of related flaviviruses. The neutralizing epitope is thus predicted to be formed by contribution of aa from domain I and II of opposing E monomers. The nature of this epitope was supported by the analysis of one wild-type YFV strain (Senegal 90) which is naturally resistant to neutralization by scFv-7A. Microneutralization assays using sera from YFV-infected patients and 17D-immunized travelers confirm the importance of E-71 in YFV neutralization but also showed that those escape variants, originally present in the vaccine lot, do not carry a risk of neutralization escape in persons who are immunized with the 17D vaccine. The potential neutralization mechanism by which these scFvs act, particularly by preventing the fusion process, and their potential use as a therapeutical tool are discussed. The structural complexity of the epitope identified in this work has implications for understanding the mechanism of antibody-mediated neutralization of YFV and these data may be useful for the design of a new recombinant yellow fever vaccine based on a cDNA-derived infectious clone
Immunotherapeutic Strategies as Potential Treatment Options for Cutaneous Leishmaniasis
No full textCutaneous leishmaniasis (CL), caused by protozoan parasites of the Leishmania genus, is prevalent in tropical and subtropical regions, with important morbidity, particularly in low- to middle-income countries. Current systemic treatments, including pentavalent antimonials and miltefosine, are associated with significant toxicity, reduced efficacy, and are frequently ineffective in cases of severe or chronic CL. Immunotherapies leverage the immune system to combat microbial infection and offer a promising adjunct or alternative approach to the current standard of care for CL. However, the heterogeneous clinical presentation of CL, which is dependent on parasite species and host immunity, may require informed clinical intervention with immunotherapies. This review explores the clinical and immunological characteristics of CL, emphasising the current landscape of immunotherapies in in vivo models and clinical studies. Such immune-based interventions aim to modulate immune responses against Leishmania, with additive therapeutic effects enabling the efficacy of lower drug doses and decreasing the associated toxicity. Understanding the mechanisms that underlie immunotherapy for CL provides critical insights into developing safer and more effective treatments for this neglected tropical disease. Identifying suitable therapeutic candidates and establishing their safety and efficacy are essential steps in this process. However, the feasibility and utility of these treatments in resource-limited settings must also be considered, taking into account factors such as cost of production, temperature stability, and overall patient access
Characterization of a major neutralizing epitope on the yellow fever virus envelope protein using human recombinant monoclonal antibody fragments generated by phage display
No full textYellow fever virus (YFV) is a mosquito-transmitted, enveloped, positive stranded RNA virus belonging to the genus flavivirus, which causes hemorrhagic fever in humans in Africa and South America. The YFV is responsible for 200 000 clinical infections per year including 40 000 deaths. Despite the presence of a highly effective YF vaccine called 17D vaccine, this disease is now strongly re-emerging and has to be considered as a public health problem. The present live attenuated 17D vaccine has two major drawbacks: 1) the ancient production method by inoculating viable embryonated eggs which limits the vaccine production capacity and, therefore, impairs attempts to control the disease and may contribute to vaccine supply shortage. 2) this vaccine is a non clonal vaccine which is constituted of heterogenous virion sub-populations. Furthermore, recent reports of several cases of viscerotropic and neurotropic disease associated with 17D vaccination have raised the obvious question of vaccine safety. Taken together, these data show that it appears essential to design a new clonal vaccine which could be based on infectious cDNA clone and produced in animal cell culture. For this purpose, the knowledge of YFV neutralizing epitopes is essential. Because YFV immunity is mainly antibody-mediated, we wanted to isolate human neutralizing antibodies specific for YFV and use them as a tool to characterize the neutralizing epitopes of YFV. The phage display technology provides one of the most convenient systems to isolate such neutralizing recombinant antibody fragments. We generated YF patient-derived antibody phage libraries which were screened against purified virions of the YFV-204-WHO vaccine strain. This step led to the isolation of several single-chain antibody fragments (scFv) which recognized conformational and pH sensitive epitopes in the envelope E protein. Three genetically closely-related and competing scFvs were found to be able to neutralize in vitro the 17D vaccine strain and five wild-type African strains of YFV. To map their epitopes, neutralization escape variants of the YFV-17D-204-WHO were generated using one high-affinity scFv (scFv-7A). Amino acids (aa) E-153, E-154 and E-155 in domain I and aa E-71 in domain II of the E protein were shown to be the critical components of one complex neutralizing epitope. These aa do not form a contiguous epitope on the monomeric E protein, but are in close vicinity in the dimeric form the E protein is predicted to adopt, based on the crystal structures of related flaviviruses. The neutralizing epitope is thus predicted to be formed by contribution of aa from domain I and II of opposing E monomers. The nature of this epitope was supported by the analysis of one wild-type YFV strain (Senegal 90) which is naturally resistant to neutralization by scFv-7A. Microneutralization assays using sera from YFV-infected patients and 17D-immunized travelers confirm the importance of E-71 in YFV neutralization but also showed that those escape variants, originally present in the vaccine lot, do not carry a risk of neutralization escape in persons who are immunized with the 17D vaccine. The potential neutralization mechanism by which these scFvs act, particularly by preventing the fusion process, and their potential use as a therapeutical tool are discussed. The structural complexity of the epitope identified in this work has implications for understanding the mechanism of antibody-mediated neutralization of YFV and these data may be useful for the design of a new recombinant yellow fever vaccine based on a cDNA-derived infectious clone
The naturally attenuated Kunjin strain of West Nile virus shows enhanced sensitivity to the host type I interferon response
No full textThe host determinants that contribute to attenuation of the naturally occurring nonpathogenic strain of West Nile virus (WNV), the Kunjin strain (WNVKUN), remain unknown. Here, we show that compared to a highly pathogenic North American strain, WNVKUN exhibited an enhanced sensitivity to the antiviral effects of type I interferon. Our studies establish that the virulence of WNVKUN can be restored in cells and mice deficient in specific interferon regulatory factors (IRFs) or the common type I interferon receptor. Thus, WNVKUN is attenuated primarily through its enhanced restriction by type I interferon- and IRF-3-dependent mechanisms
The Quest for Citations: Drivers of Article Impact
No full textWhy do some articles become building blocks for future scholars, while many others remain unnoticed? We aim to answer this question by contrasting, synthesizing and simultaneously testing three scientometric perspectives – universalism, social constructivism and presentation – on the influence of article and author characteristics on article citations. To do so, we study all articles published in a sample of five major journals in marketing from 1990 to 2002 that are central to the discipline. We count the number of citations each of these articles has received and regress this count on an extensive set of characteristics of the article (i.e. article quality, article domain, title length, the use of attention grabbers and expositional clarity), and the author (i.e. author visibility and author personal promotion). We find that the number of citations an article in the marketing discipline receives, depends upon “what one says†(quality and domain), on “who says it†(author visibility and personal promotion) and not so much on “how one says it†(title length, the use of attention grabbers, and expositional clarity). Our insights contribute to the marketing literature and are relevant to scientific stakeholders, such as the management of scientific journals and individual academic scholars, as they strive to maximize citations. They are also relevant to marketing practitioners. They inform practitioners on characteristics of the academic journals in marketing and their relevance to decisions they face. On the other hand, they also raise challenges towards making our journals accessible and relevant to marketing practitioners: (1) authors visible to academics are not necessarily visible to practitioners; (2) the readability of an article may hurt academic credibility and impact, while it may be instrumental in influencing practitioners; (3) it remains questionable whether articles that academics assess to be of high quality are also managerially relevant.Impact;Citation Analysis;Referencing;Scientometrics;Cite
Modeling Process of a Third Dimension Universe for Transportation Simulation: Application to Railway System
No full textIn past years, 3D models of virtual worlds have been used in several applications such as urban planning, simulation and design. In the railway field, that we chose as a field of application to illustrate our proposals in this article, simulation makes sense because of the complexity involved and the risk for personnel during upstream phases of validation. To be able to simulation with enough precision, the model of the virtual universe is a key point. Especially For train component simulation, an accurate and detailed model of the train component is mandatory. For training the drivers within a serious game, a high visual quality is required. Obtaining a single model supporting these two constraints at the same time at the lowest cost is still an open issue and involved many actors. Our contribution is a methodology and a process for creating a virtual universe model, based on automatic model generation, in order to allow the creation of large-scale universes while guaranteeing a level of details appropriate to the need, a model of constant quality and including semantic data necessary for simulation, while reducing the modeling costs and the modeling duration. The proposed process is applied to train simulation.Part of this work carried out under the ASTRES project supported by the Alstom Transport Company. The views and conclusions contained within this document are those of the authors, and should not be interpreted as representing the official policies, either expressed or implied, of the Alstom Transport Company.Galland, S (reprint author), Univ Bourgogne Franche Comte, UTBM, LE2I, Multiagent Grp, F-90010 Belfort, France.
[email protected]
The discovery of SycO reveals a new function for type three secretion effector chaperones
No full textThe Type Three Secretion (T3S) system is a device used by many Gram-negative pathogens that allows bacteria to deliver effector proteins straight into the eukaryotic cell cytosol. These effectors interfere with various signaling pathways to subvert the host cell functions. The secretion machinery of the T3S system consist of a basal body spanning the bacterial inner and outer membrane followed by a stiff hollow needle outside the bacterium. The fully assembled secretion apparatus constitute a continuous hollow conduit that connects the bacteria to the eukaryotic target cell. After cell contact, virulence proteins -called effectors- are injected directly into the cytosol of the host cell via the T3S apparatus. Several effectors of the T3S system require the assistance of specific cytosolic chaperones to be efficiently exported. There are three classes of T3S chaperones. Effector proteins are assisted by Class I chaperones. Although Class I chaperones are well characterized, their main function is still a matter of controversy. In this thesis, we demonstrate that orf155 encodes a specific chaperone for the effector YopO that we called SycO. We showed that SycO enhances YopO secretion in vitro and is required for translocation of YopO into infected cells. By pulldown assay we demonstrated that residues 20 to 77 of YopO are required and sufficient for SycO binding. Using crosslinking experiments and size exclusion chromatography analysis, we determined the stoichiometry of purified SycO and YopO-SycO complexes. SycO alone forms dimers in solution and the YopO-SycO complex has a 1:2 stoichiometry. These results suggested that SycO is a typical chaperone of the Class I. YopO is a serine/theronine kinase that interacts with Rho and Rac and disrupts the cytoskeleton of the target cells. YopO has been shown to localize at the cell plasma-membrane. By transfection of YopO-EGFP hybrid proteins into HEK293T cells, we demonstrated that the chaperone-binding domain (CBD) coincides with the membrane localization domain of YopO. Nevertheless, the CBD was not needed for the kinase activity of YopO. By ultracentrifugation, we also showed that the CBD causes YopO aggregation in the bacteria, when SycO does not cover it. Further, we show that the CBD of YopE and YopT also caused aggregation in the bacteria in the absence of SycE and SycT respectively. YopE, YopT and T3S effectors in other systems also act at the membrane of the eukaryotic host cell. We propose a new hypothesis concerning the role of T3S chaperones. The sub-cellular localization domain of effectors is aggregation-prone and creates the need for a chaperone inside bacteria. We propose that masking such aggregation-prone localization domains may be a general function for type III effector chaperones
Modeling Process of a Third Dimension Universe for Transportation Simulation: Application to Railway System
No full textIn past years, 3D models of virtual worlds have been used in several applications such as urban planning, simulation and design. In the railway field, that we chose as a field of application to illustrate our proposals in this article, simulation makes sense because of the complexity involved and the risk for personnel during upstream phases of validation. To be able to simulation with enough precision, the model of the virtual universe is a key point. Especially For train component simulation, an accurate and detailed model of the train component is mandatory. For training the drivers within a serious game, a high visual quality is required. Obtaining a single model supporting these two constraints at the same time at the lowest cost is still an open issue and involved many actors. Our contribution is a methodology and a process for creating a virtual universe model, based on automatic model generation, in order to allow the creation of large-scale universes while guaranteeing a level of details appropriate to the need, a model of constant quality and including semantic data necessary for simulation, while reducing the modeling costs and the modeling duration. The proposed process is applied to train simulation.Part of this work carried out under the ASTRES project supported by the Alstom Transport Company. The views and conclusions contained within this document are those of the authors, and should not be interpreted as representing the official policies, either expressed or implied, of the Alstom Transport Company.Galland, S (reprint author), Univ Bourgogne Franche Comte, UTBM, LE2I, Multiagent Grp, F-90010 Belfort, France.
[email protected]
- …
