412 research outputs found
Links between inadequate immune responses to viral infections and disease outcome in humans
No full textDeux pandémies virales touchent aujourd’hui des millions d’individus : la pandémie du Coronavirus Disease 2019 (COVID-19), causée par le Syndrome respiratoire aigu sévère coronavirus 2 (SRAS-CoV-2) et celle du Syndrome d’Immunodéficience Acquise (SIDA) causée par le Virus de l’Immunodéficience Humaine (VIH). Ces deux maladies diffèrent par leur physiopathologie, dont une meilleure compréhension a permis le développement de traitements efficaces. Pourtant, ces deux pandémies persistent. Une infection par SARS-CoV-2 peut être mortelle en raison d’une réponse immunitaire exacerbée et potentiellement retardée. Le VIH à l’inverse échappe continuellement à la réponse immunitaire, l’affaiblissant au cours des années jusqu’au développement du SIDA, ouvrant la porte à des maladies opportunistes mortelles. L’intérêt global de cette thèse était d’étudier comment la réponse immunitaire échoue pour ces deux infections.
L’objectif de la première étude était de trouver un biomarqueur sanguin robuste et fiable pour prédire le risque de mortalité des patients hospitalisés pour la COVID-19. Nous avons mesuré la quantité d’ARN viral, de cytokines et de marqueurs de dommages tissulaires, ainsi que la réponse humorale contre le virus dans des échantillons de plasma de 279 patients à travers trois cohortes. Nous avons trouvé que l’ARN viral mesuré environ 11 jours après le début des symptômes, et ajusté pour l’âge et le sexe, peut prédire la mortalité dans les 60 jours suivant le début des symptômes. Nous avons également trouvé que des fortes concentrations de cytokines inflammatoires et de marqueurs de dommages tissulaires, ainsi qu’un faible niveau d’anticorps liant le Region Binding Domain (RBD) de la protéine Spike de SARS-CoV-2, sont aussi associées à la mortalité. Dans un deuxième projet, nous nous sommes servis d’outils de réduction de dimensionnalités combinant les facteurs associés à la mortalité, permettant une stratification des patients en quatre groupes basés uniquement sur leur profil immuno-virologique plasmatique. Un seul de ces groupes est lié à une plus grande mortalité. Mis ensemble, nos travaux permettent une meilleure compréhension de l’hétérogénéité des patients hospitalisés pour la COVID-19, incluant l’identification des patients à haut risque de mortalité. Ces données pourraient servir à cibler les traitements thérapeutiques selon la réponse immunologique du patient.
Notre troisième étude portait sur l’étude de la dysfonction des lymphocytes T CD4+ spécifiques du VIH. Ceux-ci sont affaiblis par l’infection au VIH et perdent leur capacité à combattre l’infection. Notre objectif était de caractériser la réponse au blocage du point de contrôle immunitaire (BPCI - immunothérapie qui renverse partiellement la dysfonction des lymphocytes T) PD-1 parmi les divers types des lymphocytes T CD4+. Nous avons d’abord comparé l’état de dysfonction des lymphocytes chez deux cohortes de personnes vivant avec le VIH (PVVIH) non-traitées. Pour l’une des deux cohortes, la virémie est contrôlée par le système immunitaire (cohorte dite de « Contrôleurs Élites »), à l’inverse de la seconde cohorte (dite « Virémique »). Les lymphocytes T CD4+ des personnes virémiques perdent leur activité antivirale et ont une forte expression de points de contrôles immunitaires. Au contraire, les contrôleurs élites ont une charge virale indétectable en l’absence de thérapie antirétrovirale (TAR), et des lymphocytes T CD4+ relativement fonctionnels. En réponse au BPCI, les lymphocytes T CD4+ spécifiques du VIH démontrent une plus grande réponse chez les PVVIH virémiques, via l’augmentation du nombre de cellules produisant des cytokines. Chez ces individus, toutes les fonctions mesurées augmentent, à l’exception des cytokines associées aux cellules T CD4+ folliculaires auxiliaires qui sont impliquées dans l’amorçage des réponses immunologiques des lymphocytes B. Ces données montrent qu’il existe une réponse spécifique des sous-types de lymphocytes T CD4+ aux BPCI. Ce projet démontre l’avantage du blocage du ligand de PD-1 (PD-L1) sur les effets hétérogènes au niveau unicellulaire, soulignant l’importance de considérer les T CD4+ dans les analyses futures des essais cliniques évaluant le bénéfice des BPCI.
Mis ensemble, cette thèse permet une meilleure caractérisation de la réponse immunologique contre un virus à infection aiguë et, dans un second temps, un autre à infection chronique. Ces études permettent une meilleure compréhension de l’hétérogénéité dans la réponse immunologique des personnes infectées qui, si prise en compte dans des essais cliniques, pourrait aider à expliquer la variété de l’efficacité des traitements.Viral infections are a major cause of disease in humans. Pandemics refer to virulent viruses that spread across more than one continent. In the last century, two major such pandemics have occurred with still-current repercussions: the acquired immunodeficiency syndrome (AIDS) pandemic caused by the Human Immunodeficiency Virus (HIV), and the Coronavirus Disease 2019 (COVID-19) pandemic by the severe acute respiratory coronavirus 2 (SARS-CoV-2). The diseases caused by both of these viruses are very different in their pathophysiology. A better elucidation of these diseases has already allowed researchers to develop therapeutic treatments against these infections; however, both pandemics caused by these viruses are ongoing. While SARS-CoV-2 proves to ultimately be fatal by an exacerbated and perhaps delayed immune response against the virus, HIV rather evades the host’s immune response, weakening it over time until inducing a severe immunocompromised state, opening the door for fatal opportunistic diseases. The overarching goal of this thesis was to study the failings of the immune response against each virus, and extract information useful to guide therapeutic practices.
The objective of the first study was to find a robust and reproducible predictor of fatal outcome among patients hospitalized for their COVID-19. We profiled the plasma of a total of 279 patients across three independent cohorts to measure SARS-CoV-2 viral RNA, antibody responses against the virus and the quantities of inflammatory cytokines and markers of tissue damage. We found that plasma viral RNA could reproducibly predict fatal outcome on samples collected at 11 days after symptom onset, when adjusted for age and sex. Plasma vRNA’s predictive accuracy was maintained at earlier timepoints. We also found that low SARS-CoV-2-region-binding-domain (RBD)-specific IgG, low SARS-CoV-2-specific antibody-dependent cellular cytotoxicity, and elevated cytokines and injury markers were also strongly associated with mortality. In a second study using dimensionality reduction tools, we were able to separate our cohort in four distinct « patient clusters », based on their immunovirological plasma profile, with one cluster enriched in fatal outcomes. Our findings better characterize the heterogeneity of hospitalized COVID-19 cases, and may be useful in directing targeted therapeutic treatments.
In our third study, our objective was to characterize the response of dysfunctional HIV-specific CD4+ T cells to immune checkpoint blockade (ICB) across multiple subsets. We first sought to compare the functional state of HIV-specific CD4+ T cells among two cohorts of HIV-infected untreated indivduals, based on their ability to spontaneously control viral replication. Elite controllers, who have no detectable viral load in the absence of anti-retroviral therapy (ART), had more functional HIV-specific CD4+ T cells than their viremic counterparts, as well as lower levels of dysfunction-related transcription factors and immune checkpoint expression. We then compared the response of HIV-specific CD4+ T cells to ICB and saw greater increase in functionality in the dysfunctional cells of viremic individuals. All functions assessed were increased except for B-cell helping T follicular-helper-associated functions, underlying subset-specific responses to ICB. This effect was largely lost once ART was initiated, suggesting that the use of ICB would be optimal right before the initiation of ART.
Together, our results contribute to a better understanding of two pandemic-causing viral infections, and reveal key considerations for therapy
MIRACLE - A Joint DLR/ONERA Effort on Harmonization and Development of Industrial and Research Aerodynamic Computational Environment
No full textManuel Brunet i Solà (1889-1956). El periodisme d'idees al servei de la "veritat personal"
No full textThis doctoral thesis deals with the intellectual biography of the writer and journalist Manuel Brunet (Vic, 1889, Figueres, 1956). It reconstructs the life and professional studies of the author, and the most important facets of his literature and journalism. In addition, it examines his literary texts. A special emphasis has been placed on the study of journalistic production of Brunet and on the analysis of the professional profile of the author. Examination and assessment of its production has been accurate, including a classification of the items and a comparison of his journalistic style with that of other contemporary authors, both Catalan (Josep Pla and Joseph M. de Sagarra), French (Charles Maurras and Léon Daudet) and English (GK Chesterton and Hilaire Belloc). The latter part of the work analysises the condition of "victor won" of Manuel Brunet after the Spanish Civil War, and how this author is an example of a whole generation of conservative Catalan nationalist witers who lived a difficult situation after the conflict.Aquesta tesi doctoral aborda la biografia intel•lectual de l’escriptor i periodista Manuel Brunet (Vic, 1889-Figueres 1956). Reconstrueix la trajectòria vital i professional de l’autor i estudia les facetes més rellevants de la seva producció literària i periodística. A més s’hi analitzen els seus textos literaris. S’ha posat especial èmfasi en l’estudi de la producció periodística de Brunet, així com en l’anàlisi del perfil professional de l’autor. L’examen i valoració de la seva producció ha estat detinguda, amb l’agrupació dels articles per àmbits temàtics i la comparació del seu estil amb el d’altres autors contemporanis, tant catalans (Josep Pla i Josep M. de Sagarra) com francesos (Charles Maurras i Léon Daudet) i anglesos (G. K. Chesterton i Hilaire Belloc). A l’última part del treball, s’aborda l’anàlisi de la condició de “vencedor vençut” de Manuel Brunet després de la guerra, i la forma com aquest autor és exemple de tota una generació d’escriptors catalanistes conservadors que van viure una situació complicada després del conflicte
Manuel Brunet i Solà (1889-1956). El periodisme d'idees al servei de la "veritat personal"
No full textThis doctoral thesis deals with the intellectual biography of the writer and journalist Manuel Brunet (Vic, 1889, Figueres, 1956). It reconstructs the life and professional studies of the author, and the most important facets of his literature and journalism. In addition, it examines his literary texts. A special emphasis has been placed on the study of journalistic production of Brunet and on the analysis of the professional profile of the author. Examination and assessment of its production has been accurate, including a classification of the items and a comparison of his journalistic style with that of other contemporary authors, both Catalan (Josep Pla and Joseph M. de Sagarra), French (Charles Maurras and Léon Daudet) and English (GK Chesterton and Hilaire Belloc). The latter part of the work analysises the condition of "victor won" of Manuel Brunet after the Spanish Civil War, and how this author is an example of a whole generation of conservative Catalan nationalist witers who lived a difficult situation after the conflict.Aquesta tesi doctoral aborda la biografia intel•lectual de l’escriptor i periodista Manuel Brunet (Vic, 1889-Figueres 1956). Reconstrueix la trajectòria vital i professional de l’autor i estudia les facetes més rellevants de la seva producció literària i periodística. A més s’hi analitzen els seus textos literaris. S’ha posat especial èmfasi en l’estudi de la producció periodística de Brunet, així com en l’anàlisi del perfil professional de l’autor. L’examen i valoració de la seva producció ha estat detinguda, amb l’agrupació dels articles per àmbits temàtics i la comparació del seu estil amb el d’altres autors contemporanis, tant catalans (Josep Pla i Josep M. de Sagarra) com francesos (Charles Maurras i Léon Daudet) i anglesos (G. K. Chesterton i Hilaire Belloc). A l’última part del treball, s’aborda l’anàlisi de la condició de “vencedor vençut” de Manuel Brunet després de la guerra, i la forma com aquest autor és exemple de tota una generació d’escriptors catalanistes conservadors que van viure una situació complicada després del conflicte
The Creation of the Monnet Plan, 1945–1946: A Critical Re-Evaluation– ERRATUM
No full textThe original version of this article was published with the incorrect author name. The author's name should have appeared as “Luc-André Brunet”.We apologise to the authors and readers for this error and reproduce the entire corrected paper on the following pages.</jats:p
High Responsivity and Response Speed Single‐Layer Mixed‐Cation Lead Mixed‐Halide Perovskite Photodetectors Based on Nanogap Electrodes Manufactured on Large‐Area Rigid and Flexible Substrates
No full textAdv. Funct. Mater. 2019, 29, 1901371 In the initially published version of this article, the name of Akmaral Seitkhan was omitted from the final authors list. The correct author list is as follows: Dimitra G. Georgiadou,* Yen-Hung Lin, Jongchul Lim, Sinclair Ratnasingham, Akmaral Seitkhan, Martyn A. McLachlan, Henry J. Snaith, and Thomas D. Anthopoulos* The respective updated author affiliations are as follows: Dr. D. G. Georgiadou, Prof. T. D. Anthopoulos Department of Physics and Centre for Plastic Electronics Blackett Laboratory Imperial College London Exhibition Road, London SW7 2BW, UK E-mail: [email protected]; [email protected] Dr. D. G. Georgiadou, S. Ratnasingham, Dr. M. A. McLachlan Department of Materials and Centre for Plastic Electronics Imperial College London Prince Consort Road, London SW7 2BP, UK Dr. Y.-H. Lin, Dr. J. Lim, Prof. H. J. Snaith Department of Physics University of Oxford Clarendon Laboratory Parks Road, Oxford OX1 3PU, UK A. Seitkhan, Prof. T. D. Anthopoulos Division of Physical Sciences and Engineering King Abdullah University of Science and Technology (KAUST) Thuwal 23955–6900, Saudi Arabia The authors apologize for any inconvenience this error may have caused.</p
La Naissance de l'idée de photographie.
No full textLa naissance de l'idée de photographie, Paris, PUF, 2011.A milestone work that examines the democratic idea of photography and its expansion in common culture, particularly in the United States; generously illustrated.This influential text by French historian and theorist François Brunet considers the invention and history of photography as the birth of an idea, rather than a new type of image. This “idea photography” combines a logical theme—that of an art without artistry—and the democratic political promise of an art for all. Officially endorsed by the 1839 French law on the daguerreotype, this idea reverberated throughout the nineteenth century in Europe and America. Brunet shows how emerging image technologies and practices in France and Britain were linked to this logical/political construction of photography, from the earliest researches of Nicéphore Niépce, Louis-Jacques-Mandé Daguerre, and Henry Fox Talbot up to the turn of the twentieth century. The parallel development of the Kodak camera and Alfred Stieglitz's “straight” vision in the United States then fulfilled, while also depreciating, the utopian promise of photography for all. This history reached a provisional climax with the reflections on images by Ralph Waldo Emerson, Hippolyte Adolphe Taine, Sigmund Freud, Henri-Louis Bergson, and Charles Sanders Peirce, reflections that both demonstrated the novelty of photography and forecast many later debates on its technology and aesthetics.The Birth of the Idea of Photography has been enriched with more than fifty photographs, reproduced in color, from North American and European collections. This edition also features a new preface by the author
El periodismo literario de Marta Brunet. Análisis de artículos publicados en diarios y revistas entre 1920 y 1958
No full textThe present research has as its study subject the journalistic texts of the Chilean-Spanish writer Marta Brunet, National Literature Award in 1961.
Born in Chillán as the daughter of Spanish landowners, the writer started in the early 1920s a prolific literary career with novels such as Montaña Adentro, María Nadie and Amasijo, which earned her a prominent place in both the Chilean and Latin American literary and intellectual scenes.
Simultaneously, between 1920 and 1958 she developed a more unknown career as a reporter and director of media in Chilean and foreign newspapers and magazines, such as El Día, La Discusión, El Sur, La Hora, Familia, Ecrán, Repertorio Americano and Atenea.
The journalistic texts of Marta Brunet correspond with the formats known as chronicles, columns and interviews. Several of them -especially the ones related to cooking duties and the role of the woman in the domestic world- were published under the names of Miriam, Isabel de Santillana, Hermanita Hormiga and Aladina. In others, however, she used her real name and allows evidence of her vision about arts and the Chilean cultural life of the early 20th century, childhood and the Chilean women's demands for a bigger presence in the public world.
This study aims to analyze the journalistic works of the author from a corpus retrieved from historical archives and that have been transcribed and processed with text analysis and narratology techniques.
I have distinguished four great concerns of the author throughout her career as a journalist, that for the purposes of this study they were established in three stages: "Reporter in formation" (1919-1924), "Prolific journalist" (1926-1939) and "Mature journalist" (1939-1967).
During these three periods the writer-journalist consistently touches subjects that were grouped into four categories: "Arts and letters", "Woman in the public and private world", "Infancy" and "Travels and daily life".
The analysis revealed that Brunet is predominantly located in an homodiegetic narrator and assumes a leading role in her stories, with the first person as a distinctive characteristic of her journalism.
It is possible to point out -as a contribution of the journalism of Marta Brunet- the visibility in the public scene of women and children as another individual that had been ignored by society until then. Through the use of pen- names, Brunet builds and projects female sensibilities that experiment identity tensions throughout the first half of the 20th century, such as the dilemma between the maintenance of domestic roles and the breaking into the salaried world.
On the other hand, her journalistic writing reveals that the author uses the description of environments and characters, use of text blocks and dialogues as resources to create her journalistic pieces, just like the literary journalists of the 21st century (Caparrós 2016).
Marta Brunet enjoyed the profession. In her chronicles, columns and interviews it is not a mere incorporation of fiction resources that we see, but rather elements that place her as one of the precursors of the modern Chilean literary journalism.
References
Amaro, Lorena. “En un país de silencio: narrativa de Marta Brunet”. Obra Narrativa. Novelas. Tomo I. Ediciones Universidad Alberto Hurtado, 2014.
Caparrós, Martín. Lacrónica. Editorial Planeta, 2016.
Gálvez, Karim. Marta Brunet. Crónicas, columnas y entrevistas. La Pollera Ediciones, 2019.
Kholer Riessman, Catherine. Narrative methods for the human sciences. Sage Publications, 2008.
Rama, Ángel. “Marta Brunet Premio Nacional de Literatura”. Marcha, 18 de febrero de 1962, pp. 21–22.
Rotker, Susana. La invención de la crónica. Ediciones Letra Buena, 1992.La presente investigación ha analizado los textos periodísticos de la escritora chilena Marta Brunet, Premio Nacional de Literatura 1961.
Nacida en Chillán como hija de terratenientes españoles, la escritora inició a principios de los años 20 una prolífica carrera literaria con novelas como Montaña Adentro, María Nadie y Amasijo, que le valió un lugar destacado en el ambiente literario chileno y latinoamericano.
En paralelo, entre 1920 y 1958, desarrolló una carrera más desconocida como reportera y directora de medios en diarios y revistas chilenos y extranjeros, como El Día, La Discusión, El Sur, La Hora, Familia, Ecrán, Repertorio Americano y Atenea.
Los textos periodísticos de Marta Brunet corresponden a los formatos conocidos como crónicas, columnas y entrevistas. Varios de ellos –especialmente los relacionados con menesteres culinarios y el rol de la mujer en el mundo doméstico— los publicó bajo los seudónimos de Miriam, Isabel de Santillana, la Hermanita Hormiga y Aladina. En otros, sin embargo, utilizó su nombre real y permiten evidenciar su visión sobre las artes y vida cultural chilena de principios del siglo XX, la infancia y las demandas de la mujer chilena por mayor presencia en el mundo público.
Este estudio analizó la obra periodística de la autora a partir de un corpus rescatado desde archivos históricos y que han sido transcritos y procesados con técnicas de análisis narrativo.
He distinguido cuatro grandes preocupaciones de la autora a lo largo de su trayectoria como periodista, que para este estudio fueron establecidas en tres etapas: “Reportera en formación” (1919-1924); “Periodista prolífica” (1925-1939) y “Periodista en su madurez” (1939-1967).
Durante estos tres periodos la escritora-periodista, de manera consistente, aborda temáticas que fueron agrupadas en cuatro categorías: “Artes y letras”; “Mujer en el mundo público y privado”; “Infancia”; y “Viajes y vida cotidiana”.
El análisis reveló que Brunet se ubica predominantemente como narradora homodiegética y asume un rol protagonista en sus relatos, con la primera persona como una característica distintiva de su periodismo.
Es posible señalar -como un aporte del periodismo de Marta Brunet- la visibilización en la escena pública de mujeres y niños como un otro individual hasta entonces ignorado por la sociedad. A través del uso de seudónimos, Brunet construye y proyecta sensibilidades femeninas que experimentan tensiones identitarias durante la primera mitad del siglo XX, tales como: el dilema entre la mantención de los roles domésticos y la irrupción en el mundo asalariado.
Por otro lado, su escritura periodística reveló que la autora recurre a la descripción de ambientes y personajes, uso de bloques de textos y diálogos como recursos para elaborar sus piezas periodísticas, tal como los periodistas literarios del siglo XXI (Caparrós 2016)
Marta Brunet disfrutó de la profesión. En sus crónicas, columnas y entrevistas no se aprecia una mera incorporación de recursos de ficción, sino elementos que la sitúan como una de las precursoras del periodismo literario chileno moderno.
Bibliografía
Amaro, Lorena. “En un país de silencio: narrativa de Marta Brunet”. Obra Narrativa. Novelas. Tomo I. Ediciones Universidad Alberto Hurtado, 2014.
Caparrós, Martín. Lacrónica. Editorial Planeta, 2016.
Gálvez, Karim. Marta Brunet. Crónicas, columnas y entrevistas. La Pollera Ediciones, 2019.
Kholer Riessman, Catherine. Narrative methods for the human sciences. Sage Publications, 2008.
Rama, Ángel. “Marta Brunet Premio Nacional de Literatura”. Marcha, 18 de febrero de 1962, pp. 21–22.
Rotker, Susana. La invención de la crónica. Ediciones Letra Buena, 1992.Escuela de DoctoradoDoctorado en Español: Lingüística, Literatura y Comunicació
Cartas a un editor: la correspondencia de Marta Brunet a Samuel Glusberg en la década del veinte
No full textThis paper goes through the unpublished letters from Marta Brunet to Samuel Glusberg during the twenties in order to examine the self-management strategies the author exhibits in them and that partly determine the reception of her writing in transnational circuits. It is postulated that in these “editorial letters” (Mosqueda 2018) there is an exchange between two intellectuals who consider themselves writing professionals in their respective cultural fields, which allows a symmetrical collaboration, without involving the insertion strategies traditionally used by Latin American woman writers of the first half of the 20th century (Fletcher 2004), as Brunet herself did in Chile before publishing her first novel Montaña adentro. Although Brunet trusts certain mediations on Glusberg for the dissemination of her work in Argentina, the editor also relies on her as a kind of correspondent who has an expert opinion on local writers, can provide press clippingsfor the reception of his own editions in Chile and personal impressions about literary figures and events.Este artículo revisa las cartas inéditas de Marta Brunet al editor Samuel Glusberg durante la década del veinte para indagar en las estrategias de autogestión que la escritora exhibe en ellas y que determinan en parte la recepción de su escritura en circuitos transnacionales. Se postula que en estas “cartas editoriales” (Mosqueda 2018) asistimos a un intercambio entre dos intelectuales que se consideran profesionales de las letras en sus respectivos campos, lo que permite una colaboración simétrica, que no pasa por las estrategias de inserción que tradicionalmente emplearon las escritoras latinoamericanas de la primera mitad del siglo XX (Fletcher 2004), como hizo la misma Brunet en Chile antes de la publicación de su primera novela Montaña adentro. Si bien Brunet confía ciertas mediaciones en Glusberg para su difusión en Argentina, el editor ve en ella una especie de corresponsal a quien le pide su opinión sobre escritores locales, recortes de prensa sobre la recepción de sus propias ediciones en Chile e impresiones personales sobre personajes y acontecimientos literario
Foucault’s governmentality and the issue of project collaboration
No full textThe concept of governmentality has proven useful to analyse how the reflexive management of people within and without the project is conducted. In this chapter we explore the organizational theory of governmentality and its importance in project settings. First, we identify the specificity of project governance and relate it to the definition and discussion of governmentality by Michel Foucault. Following this, the use of governmentality within projects through project culture is discussed. Subsequently, the use of governmentality outside projects through social media is discussed. Finally, the chapter concludes by highlighting new directions for research with governmentality as the focal point, discussing the types of research questions that a concern with projects and governmentality raises and how addressing these might further develop project management as a field of enquiry.Green Open Access added to TU Delft Institutional Repository 'You share, we take care!' - Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public.Integral Design & Managemen
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