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The presence of the cave bear Ursus ingressus in northern Italy is a question that, at present, is still debated. The discovery of U. ingressus fossils in the Steigelfadbalm Cave located in Vitznau, Lucerne, Switzerland allows us to provide additional insights into the possible distribution of U. ingressus into the northern regions of Italy. Here we compare the morphometry and morphodynamic data between the teeth and the metapodial bones of the Swiss cave bears, with those extracted from some Italian caves: Grotta del Bandito and Sambughetto Valstrona in Piedmont, Buco dell’Orso, Valsolda and Buco del Frate in Lombardy, Covoli di Velo and San Donà di Lamon in Veneto and, lastly Conturines in Tyrol. Our results have found only a few weak differences in morphometry and morphodynamic of the studied teeth and therefore do not support the possible presence of U. ingressus, at least in these caves.

In this study, the teeth of cave bears from the Valsolda (Como province, near the boundary with Switzerland) have been morphologically and morphodynamically studied in order to indicate the possible evolutionary level of this population. These bears belong to the spelaeus group, and are found within the range of the Italian Alps populations that are generally characterized by medium size, at times higher, but featuring a rather simple dental surface with low or intermediate morphodynamic indices, and consequently a medium or in some case low evolutionary level. With these data only, it is impossible to define the species or subspecies (ingressus?, spelaeus ladinicus?) for the bears from Valsolda.

URL del artículo en la web de la Revista: https://www.upo.es/revistas/index.php/ambigua/article/view/2647, Nel presente lavoro si analizzano gli strumenti narrativi e documentari che due registe, Elvira Dones e Karin Michalski, mettono in campo presentando un caso singolare di rottura delle categorie di genere: la ¿vergine giurata¿ del Kanún dell¿Albania. S¿identificheranno le implicazioni di due strategie espositive: comparazione di casi simili e contrasto di casi strutturalmente differenti. Si applicherà in modo non dogmatico il modello di analisi enunciativa del documentario come istanza esplicativa proposto da Bill Nichols. Il risultato sarà l¿esemplificazione dei rapporti sotterranei che legano elementi narrativi e che possono esser interpretati come strategie di riconoscimento dell¿alterità., En este trabajo se analizan las herramientas narrativas y documentales que dos directoras de cine, Elvira Dones y Karin Michalski, ponen en escena presentando un caso singular de ruptura de las categorías de género: la figura de la ¿virgen jurada¿ del Kanún de Albania. Se identificarán las implicaciones de dos estrategias expositivas: la comparación de casos similares y el contraste de casos estructuralmente diferentes. Se aplicará de forma no dogmática el modelo de análisis enunciativo del documental como instancia explicativa propuesto por Bill Nichols. El resultado será la ejemplificación de las relaciones que conectan de forma argumentativa subliminal elementos narrativos dentro del documental y que se pueden interpretar como estrategias para el reconocimiento de la alteridad., The purpose of this paper is to analyze the narrative and documentary tools used by two filmmakers, Elvira Dones and Karin Michalski, to illustrate a special case of breaking gender stereotypes: the ¿sworn virgin¿ of the Kanún of Albania. The focus was set on the implications of two different strategies: comparing similar cases and contrasting structurally different cases. By applying, in a non-dogmatic way, Bill Nichols' model of the analysis of enunciation in documentary films, this paper aims to exemplify the subliminal relations between the different narrative elements and to interpret them as strategies of recognition of otherness., Universidad Pablo de Olavide

Nel saggio si pone il problema della valutazione dell'autotraduzione in una prospettiva che analizza le molle che nel profondo muovono un testo letterario. Si analizza l'autotraduzione assistita del romanzo breve di Ornela Vorpsi Il paese dove non si muore mai dal francese all'italiano prendendo in considerazione la presenza di marche di genere in passi in cui siano presenti oggetti; la questione di genere percorre tutto il testo e quindi appare interessante verificare come questa si cristallizzi in significanti apparentemente poco permeabili alla modulazione denotativa e connotativa. Si giungerà alla conclusione che l'analisi dell'autotraduzione assistita può esser strumento valido per la definizione del grado di coerenza delle strutture profonde di un testo tanto più importante se la tematica è centrata sulla questione di genere. Abstract. This article approaches the problem of how to evaluate the significance of the critical feminist instances on an assisted self-translation text by applying the contrastive analysis method. The analysed work is O. Vorpsi novel Il paese dove non si muore mai, which has been translated from Italian to French by M. Pozzoli, with the author’s collaboration. The main aspect which will be analysed is the to investigate the presence of gender marks in passages which mention objects – informative and at the same time formative elements of the text-, since the gender issue crystallize in a particular way also in signifiers of an apparently low permeability to the connotative modulation, as it is the case for those signifiers related to objects. By contrasting the oscillations between the two texts, we will emphasize on the possible contradictions in the text’s deep-lying structure. In this way, through the assisted self-translation analysis it can be measured to what extent the intended critical instances regarding the gender issue which are present throughout the novel are coherent and valid.

Gabriella Ghermandi è scrittrice che in alcune sue opere mette in scena più voci: infatti, l'autrice post-coloniale italo-etiope, attraverso una scrittura intrisa di autobiografia, dà voce alla storia del popolo al quale appartiene per ascendenza materna e, così facendo, tenta di riscrivere in forma corale la misconosciuta recente storia coloniale italiana. Nella lettura qui proposta si cercherà di mettere in rilievo l’originalità dell’opera di Ghermandi anche attraverso il confronto con la riflessione di Walter Benjamin (Der Erzähler) e di Judith Butler (Antiogone’s Claim). Gabriella Ghermandi is a writer who in some of her works puts several voices on the stage: in fact, the Italian-Ethiopian post-colonial author, through an autobiographical writing, gives voice to the history of the people of her maternal ancestors and, in that way, she tries to rewrite in a choral form the unrecognized recent Italian colonial history. In the following proposed reading we will try to put in relief the originality of Ghermandi’s work by comparison with the reflection of Walter Benjamin (Der Erzähler) and Judith Butler (Antigone's Claim).

International audience; In this work the heavy ion induced Single Event Upset (SEU) cross-sections and resulting failure rates of SRAM memory components were studied.

Pese a ser profesionales muy preparados en las áreas técnicas, muchos de los docentes de la Carrera de Ingeniería Civil de la Universidad Católica de Santiago de Guayaquil no se han actualizado en aspectos de docencia y tecnología de acuerdo a los tiempos actuales. La bibliografía refiere experiencias sobre capacitación, actualización y perfeccionamiento docente en situaciones similares, establecimiento de condiciones para optimizar el aprendizaje en la educación superior y medidas para su sistematización. La normativa legal ecuatoriana y la reglamentación de la Universidad actual, referente a la calidad de la educación superior demandan mejoras urgentes acordes con su imagen institucional. Se ha realizado una investigación para determinar las necesidades de capacitación, actualización y perfeccionamiento de los docentes de la Carrera, para analizar la relación entre el perfeccionamiento docente y la formación profesional que requieren los estudiantes y diseñar un sistema de capacitación alternativo. Se usaron la revisión bibliográfica y la encuesta, sobre una población y muestra de profesores del semestre A del 2012, bajo la modalidad proyecto factible y el tipo descriptivo y evaluativo. Se presentan conclusiones y recomendaciones para ser aplicadas en la Carrera. Se aprueba la hipótesis de que más del 65% de los informantes de la carrera de ingeniería civil expresan la necesidad de capacitación, actualización y perfeccionamiento. Se presenta una propuesta para la implementación de un sistema de capacitación alternativo que busca sostener en el tiempo la actualización y perfeccionamiento de los docentes, mejorar su capacitación y elevar su nivel de formación pedagógica, con el fin de beneficiar a los estudiantes de la Carrera de Ingeniería Civil. Palabras clave: Capacitación, actualización, perfeccionamiento, docente, sistema, alternativo.

L'importance relative des champs acoustiques direct et réverbéré est fondamentale pour la qualité d'écoute de la musique dans les espaces consacrés à la musique. A témoin, les indices acoustiques de clarté C de Alim, de définition D de Thiele, de rapport signal sur bruit de Lochner et Burger, etc. De fait, dans les édifices religieux existants et accueillant des concerts de musique sacrée avec chœur, solistes et orchestre, il n'est guère possible de déduire de la mesure de ces indices la disposition et les positions optimales des exécutants. Le plus souvent diverses contingences sans rapport avec les critères d'écoute dictent les choix. La comparaison expérimentale du champ réverbéré dans différentes configurations a montré que celui-ci dépendait beaucoup plus qu'admis par les modèles simples déduits des lois de Sabine et que cela n'était pas sans conséquence pour les conditions d'écoute, notamment relativement aux réflexions précoces, car cela implique une dépendance des distances critiques en fonction de la position des musiciens et chanteurs. Cela revêt une importance particulière dans la Cathédrale de Lausanne : en effet une assistance électroacoustique y crée des pseudo-réflexions précoces - sans cette dernière clarté et intelligibilité sont notoirement insuffisantes -, dont les amplitudes ont été planifiées en fonction du champ réverbéré. Ce dernier est simplement caractérisé par des spectres 1/3 ou 1/1 octave en fonction de la position du source de puissance acoustique de référence.

Le problème de l'accordage du piano a reçu bien des réponses dont la plus célèbre et la plus universelle se base sur le clavecin bien tempéré selon Bach. On sait que la gamme chromatique également tempérée permet la transposition dans tous les tons au prix du non-respect des intervalles qui présentent tous une certaine dureté, hormis l'octave. Cordier a proposé une gamme dans laquelle les quintes sont toutes justes avec en conséquence des octaves trop grandes. Pour objectiver les réactions à ces deux tempéraments, aussi bien des musiciens que des auditeurs, une expérimentation systématique a été menée à bien. Dans un premier temps, on a procédé à l'enregistrement d'extraits du répertoire pianistique bien choisis, en respectant les unités de temps, de lieu et d'action : même piano accordés selon l'un puis l'autre tempérament par un accordeur expert ; mêmes studio et microphones avec le même opérateur ; même pianiste concertiste ; durée totale d'une matinée. L'enregistrement d'une durée totale de 40 minutes environ a été soumis à plusieurs dizaines d'auditeurs, soit en leur mettant à disposition un CD pour une écoute individuelle - cas des musiciens professionnels et des gens des métiers du son -, soit en le diffusant en cours - étudiants en acoustique. Bien entendu, l'écoute se faisait en aveugle. Pour chaque extrait, il était demandé si une différence était perçue entre les deux versions, et si oui, laquelle était éventuellement préférée. Subsidiairement, on demandait à chacun de se classer en musicien professionnel ou amateur - en spécifiant l'instrument principal -, en mélomane averti ou amateur. L'analyse des questionnaires a conduit à de très intéressants constats ; par exemple, les pianistes préfèrent en majorité l'accordage de Cordier, alors que les violonistes préfèrent celui usuel. Quant aux mélomanes, mêmes avertis, ils sont souvent peu réceptifs à l'accordage.

Toute production de musique ou de parole dans un espace clos fait intervenir en amont des questionnements d’acoustique. Pour offrir à l’auditeur des conditions d’écoute optimales, l’acousticien utilise des descripteurs caractérisant le champ sonore. Les méthodes usuelles basées sur la réponse impulsionnelle ou l’échogramme, selon le principe d’acoustique géométrique, permettent de calculer des indices pour la qualification de la salle (temps de réverbération, clarté, rapport S/N, dispersion des réflexions précoces, etc.). Ces indices ne suffisent toutefois pas pour des salles à géométrie complexe, particulièrement lorsque les densités et distributions temporelles des rayons d’un échogramme sont telles que l’interprétation de ce dernier est trop difficile, voire impossible. Dans ce cas, l’expertise acoustique ne peut être menée à bien qu’à l’aide de modélisations numériques puis par comparaison directe des mesures et des simulations. Nous avons simplifié ce problème par la mesure d’échogrammes spatialement distribués : un réseau omnidirectionnel de microphones, couplé à un modèle source‐image restreint, permet de tirer profit des informations temporelles et spatiales des rayons détectés. En effet, la discrimination spatio‐temporelle ou chrono‐goniométrie des rayons détectés permet la reconstruction inverse de leur trajet acoustique. Elle délivre une information globale sur le trajet entre la source et le réseau de microphones, et locale, pour les surfaces de réflexion identifiées. Ce principe a été validé par simulation puis par traitement de cas réels : d’abord dans une salle‐test rectangulaire avec ou sans traitement absorbant de ses parois, puis dans les salles d’audition d’un Conservatoire de musique et enfin, dans un espace commercial en vue de la production d’un concert classique. Les résultats obtenus valident le procédé et mettent en évidence ses apports, mais aussi les difficultés de mise en oeuvre. Enfin, ce principe a été appliqué à la consolidation des valeurs optimales des temps de dispersion des premières réflexions.

Concilium, Bd. 10 Nr. 11 (1974): Concilium: Internationale Zeitschrift für Theologie, Band 10, Heft 11

Concilium, Bd. 10 Nr. 12 (1974): Concilium: Internationale Zeitschrift für Theologie, Band 10, Heft 12

Le problème de l’accordage du piano a reçu bien des réponses dont la plus célèbre et la plus universelle se base sur le clavecin bien tempéré selon Bach. On sait que la gamme chromatique également tempérée permet la transposition dans tous les tons au prix du non-respect des intervalles qui présentent tous une certaine dureté, hormis l’octave. Cordier a proposé une gamme dans laquelle les quintes sont toutes justes avec en conséquence des octaves trop grandes. Pour objectiver les réactions à ces deux tempéraments, aussi bien des musiciens que des auditeurs, une expérimentation systématique a été menée à bien. Dans un premier temps, on a procédé à l’enregistrement d’extraits du répertoire pianistique bien choisis, en respectant les unités de temps, de lieu et d’action : même piano accordés selon l’un puis l’autre tempérament par un accordeur expert ; mêmes studio et microphones avec le même opérateur ; même pianiste concertiste ; durée totale d’une matinée. L’enregistrement d’une durée totale de 40 minutes environ a été soumis à plusieurs dizaines d’auditeurs, soit en leur mettant à disposition un CD pour une écoute individuelle - cas des musiciens professionnels et des gens des métiers du son -, soit en le diffusant en cours – étudiants en acoustique. Bien entendu, l’écoute se faisait en aveugle. Pour chaque extrait, il était demandé si une différence était perçue entre les deux versions, et si oui, laquelle était éventuellement préférée. Subsidiairement, on demandait à chacun de se classer en musicien professionnel ou amateur – en spécifiant l’instrument principal -, en mélomane averti ou amateur. L’analyse des questionnaires a conduit à de très intéressants constats ; par exemple, les pianistes préfèrent en majorité l’accordage de Cordier, alors que les violonistes préfèrent celui usuel. Quant aux mélomanes, mêmes avertis, ils sont souvent peu réceptifs à l’accordage.

Tesis (Doctora en Ciencias Químicas) - - Universidad Nacional de Córdoba. Facultad de Ciencias Químicas, 2022. Resumen: La enzima arginil-ARNt transferasa (Ate1) cataliza la transferencia de arginina desde un ARN de transferencia a una proteína aceptora. Este proceso conocido como arginilación postraduccional está involucrado en el catabolismo de proteínas, particularmente en la señalización de sustratos del sistema de degradación ubiquitina-proteasoma (UPS). En situaciones donde el UPS está comprometido, la célula activa el mecanismo proteolítico de autofagia para evitar la acumulación de especies tóxicas y mantener el fitness celular. No obstante, se desconoce si la arginilación es necesaria para el reconocimiento y la degradación de proteínas por la vía autofágica. Por este motivo, en este trabajo de tesis se propuso investigar la implicancia funcional de Ate1 en la autofagia. Se analizaron aspectos moleculares y celulares de las distintas variantes alternativas de la enzima durante la respuesta autofágica inducida por la inhibición del proteasoma. Utilizando diferentes metodologías, se demostró que las isoformas de Ate1 se localizan en el citosol y núcleo de la célula, mientras que una fracción de las mismas se une a membranas biológicas y proteínas del citoesqueleto. Esta distribución se correlaciona con la formación de estructuras de alto peso molecular, que se localizan en las proximidades del núcleo junto a la proteína adaptadora autofágica p62 y otros sustratos de degradación. Dada la importancia de p62 en el reconocimiento de sustratos, la compartimentación de Ate1 junto a esta proteína sugiere que podría ser necesaria durante la respuesta autofágica. Además, para comprender la implicancia biológica de la enzima en este proceso degradativo, se analizó la actividad autofágica en ausencia de Ate1, y frente a la expresión endógena y ectópica de la enzima en células. Con esta finalidad, se realizaron ensayos bioquímicos y de microscopía confocal que permitieron descubrir aspectos funcionales de la enzima. Se demostró que en ausencia de Ate1, el complejo mTORC1 está hiperactivado, lo cual disminuye el flujo de autofagia y provoca la acumulación de vacuolas y sustratos autofágicos en la célula. Además, se observaron defectos en la inducción de autofagia en condiciones de déficit nutricional. La expresión ectópica de una única isoforma de Ate1 permitió recuperar parcialmente el fenotipo salvaje. Este estudio sugiere que Ate1 podría contribuir al proceso de reconocimiento de los sustratos junto a p62 y permite establecer la importancia de la arginilación en la regulación del proceso de degradación autofágico. Abstract: arginyl-tRNA transferase (Ate1) enzyme catalyzes the transfer of arginine from a transfer RNA to an acceptor protein. This process known as post-translational arginylation is involved in protein catabolism, notably during substrates recognition by the ubiquitin-proteasome degradation system (UPS). When the UPS is compromised, cells activate autophagy, a proteolytic mechanism that prevents the accumulation of toxic species and maintains cellular homeostasis. To further investigate whether protein arginylation is required in this process, this work was focused on the functional implication of Ate1 in the autophagic pathway. Molecular and cellular aspects of Ate1 isoforms were analyzed during the autophagic response induced by proteasome inhibition using different experimental approaches. Ate1 isoforms were found in the cytosol and nucleus of the cell, whereas a fraction was associated with biological membranes and cytoskeleton proteins. This subcellular distribution correlates with the formation of high molecular weight structures, which are localized in the perinuclear region of the cell together with the autophagic adaptor protein, p62 and other degradation substrates. Given the importance of p62 in substrate recognition, the compartmentalization of Ate1 with this protein suggests that it may be required during autophagic response. To understand the biological implication of Ate1 in this degradative process, we assessed autophagic activity in the absence of the enzyme, and under endogenous or ectopic expression of Ate1 in cultured cells. Ate1 deletion causes mTORC1 complex hyperactivation, a decrease of autophagic flux and leads to an accumulation of autophagosomes and their substrates. Moreover, autophagic induction is impaired under fasting conditions. The observed phenotype can be partially rescued by reintroduction of stably expressed Ate1-specific isoform. Finally, this study suggests that Ate1 may contribute to the substrate recognition process together with p62 and highlights the importance of post-translational arginylation in the regulation of the autophagic degradation process. 2024-06-30 Fil: Bonnet, Laura Vanesa. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas; Argentina.

We study the cosmological constraints on the variation of the Newton's constant and on post-Newtonian parameters for simple models of scalar-tensor theory of gravity beyond the extended Jordan-Brans-Dicke theory. We restrict ourselves to an effectively massless scalar field with a potential $V \propto F^2$, where $F(��)=N_{pl}^2+����^2$ is the coupling to the Ricci scalar considered. We derive the theoretical predictions for cosmic microwave background (CMB) anisotropies and matter power spectra by requiring that the effective gravitational strength at present is compatible with the one measured in a Cavendish-like experiment and by assuming adiabatic initial condition for scalar fluctuations. When comparing these models with $Planck$ 2015 and a compilation of baryonic acoustic oscilation (BAO) data, all these models accomodate a marginalized value for $H_0$ higher than in $��$CDM. We find no evidence for a statistically significant deviation from Einstein's general relativity. We find $��< 0.064$ ($|��| < 0.011$) at 95 % CL for $��> 0$ (for $��< 0$, $��\ne -1/6$). In terms of post-Newtonian parameters, we find $0.995 < ��_{\rm PN} < 1$ and $0.99987 < ��_{\rm PN} < 1$ ($0.997 < ��_{\rm PN} < 1$ and $1 < ��_{\rm PN} < 1.000011$) for $��>0$ (for $��< 0$). For the particular case of the conformal coupling, i.e. $��=-1/6$, we find constraints on the post-Newtonian parameters of similar precision to those within the Solar System., 17 pages, 24 figures, 2 tables; small changes, updated references, matching published version in Phys. Rev. D

La formación y progresión de tumores está regulada en última instancia por la abundancia y la actividad de factores proteicos oncogénicos o supresores tumorales. En línea con esto se ha demostrado que la proteólisis irregular de factores proteicos implicados en la regulación del ciclo celular, la transcripción génica y la apoptosis contribuye a la transformación oncogénica y a la carcinogénesis. En células eucariotas, la homeostasis proteica está finamente regulada por el Sistema Ubiquitina/Proteosoma (Ubiquitin Proteosome System, UPS), que consiste en una compleja red enzimática encargada de transferir moléculas de ubiquitina a un sustrato y de este modo promover su degradación a través del proteosoma o modular su ubicación espacio temporal en una vía celular determinada. Por lo tanto, el estudio a nivel molecular de la cascada de ubiquitinación, junto con el desarrollo de compuestos que modulan componentes específicos del UPS, podrían facilitar el desarrollo y mejoramiento de nuevos y mejores tratamientos de distintas patologías. En este sentido, las ligasas de ubiquitina (o E3s) son excelentes candidatas debido a que estas enzimas son los efectores finales de la cascada de ubiquitinación y dictan la especificidad de la maquinaria del UPS. La E3 ligasa CRL4^Cdt2 desempeña un rol fundamental en la regulación de la replicación y reparación del ADN, en condiciones normales como así también en respuesta al daño al ADN. Diferentes evidencias indican que las alteraciones en los niveles de CRL4^Cdt2 pueden contribuir a la aparición y progresión del cáncer. Todos los sustratos conocidos de CRL4^Cdt2 tienen un dominio PIP (PCNA Interacting Protein) que interactúa con PCNA (Proliferating Cell Nuclear Antigen) asociado a la cromatina, y es precisamente la unión de los sustratos a PCNA lo que asegura su degradación. Por este motivo, con el objeto de identificar nuevos sustratos de CRL4^Cdt2 que permitan ahondar en el mecanismo molecular de acción de este complejo, se realizó una purificación por afinidad en tándem de Cdt2 sobre-expresado y posterior espectrometría de masa en tándem en la fracción cromatínica. A partir de estos resultados se escogieron distintos candidatos teniendo en cuenta la frecuencia de aparición de los mismos en las distintas purificaciones y se logró validar la interacción de Cdt2 sobre-expresado en la cromatina con G9a y GLP. Estas proteínas son metiltransferasas de histonas que catalizan la mono y la dimetilación de la Histona 3 en la Lisina 9, esta marca epigenética se encuentra relacionada con silenciamiento transcripcional y es indispensable para la constitución de la heterocromatina. Debido a que G9a tiene la capacidad de metilar también proteínas no histónicas realizamos un análisis de modificaciones postraduccionales de Cdt2 en una línea control y en líneas knockout que no expresan G9a y GLP (generadas por el sistema CRISPR/Cas9), donde no se encontraron péptidos de Cdt2 metilados diferencialmente en la línea control, aunque se requieren estudios adicionales y más detallados para obtener una respuesta más sólida y definitiva. Logramos identificar y validar la interacción de Cdt2 con otras dos proteínas que interactúan con el complejo G9a/GLP y median su interacción con el ADN. Utilizando ARN de interferencia de Cdt2 comprobamos que la vida media de las proteínas que forman parte de este complejo no se encuentra regulada por esta E3 ligasa, así como tampoco la localización subcelular. Debido a que el silenciamiento de Cdt2 ocasiona re-replicación e inestabilidad genómica, desarrollamos también una línea celular que no expresa Cdt2 endógeno y expresa una construcción Cdt2-Flag que es inducible con doxiciclina. Los experimentos de vida media en diferentes clones de esta línea celular confirmaron los resultados obtenidos con ARN de interferencia. Por último, es importante destacar que CRL4^Cdt2 también cumple un rol importante en la regulación de la respuesta celular a estrés genotóxico. Asimismo, recientemente se ha reportado que G9a interviene en la regulación de la respuesta al daño al ADN. Por lo tanto, estamos actualmente estudiando si la interacción funcional entre CRL4^Cdt2 y G9a/GLP posee una función importante en la modulación de la respuesta celular a distintos daños. En este sentido hemos obtenidos resultados preliminares muy alentadores. Esperamos que en estudios posteriores podamos ahondar en la caracterización molecular del eje CRL4Cdt2/G9a y la función que cumple en el control de la integridad genómica. The formation and progression of tumors is ultimately regulated by the abundance and activity of oncogenic protein factors or tumor suppressors. Accordingly, aberrant proteolysis of substrates involved in the regulation of cell cycle, gene transcription, and apoptosis has been shown to contribute to carcinogenesis. In eukaryotic cells, protein homeostasis is tightly regulated by the Ubiquitin Proteasome System (UPS), which consists of a complex enzymatic network responsible for transferring molecules of ubiquitin to a substrate and thereby promote its degradation through proteasome or modulate its spatio-temporal localization in a specific cell pathway. Therefore, the molecular study of ubiquitination cascades, together with the development of compounds that modulate specific components of the UPS, could facilitate the development and improvement of new and better strategies for the treatment of different pathologies. Accordingly, the ubiquitin ligase protein group (or E3s) represents an excellent candidate, because these enzymes are the final effectors of the ubiquitination cascade and thus dictate the specificity of UPS machinery. E3 ligase CRL4^Cdt2 plays a key role in the regulation of DNA replication and repair, in normal conditions as well as in response to DNA damage. Different lines of evidence indicate that alterations in the levels of CRL4Cdt2 may contribute to the onset and progression of cancer. All known substrates of CRL4^Cdt2 have a PIP domain (PCNA Interacting protein) that interacts with PCNA (Proliferating Cell Nuclear Antigen) associated with chromatin, and it is precisely the binding of the substrates to PCNA which ensures its timely degradation. Hence, with the aim to gain further insight into the molecular mechanisms of action of CRL4^Cdt2, we performed a tandem affinity purification of overexpressed Cdt2 and subsequent tandem mass spectrometry using only the chromatin cellular fraction. Using this strategy, among the most abundant putative Cdt2 protein interacting factors, we identified and validated the interaction between overexpressed Cdt2 and G9a/GLP. These two proteins are histone methyltransferases that catalyze the mono and dimethylation of Histone 3 in Lysine 9, which plays an important role in the transcriptional silencing process and is necessary for heterochromatin domains formation. G9a has also the ability to methylate non-histone proteins, and for this reason we performed post-translational modifications analysis of Cdt2 on knockout cell lines that do not express G9a and GLP, that were generated by the CRISPR/Cas9 system. So far, we do not find significant differences between normal and knockout cell lines although further and more detailed studies are required to obtain a more robust and definitive answer. We were able to identify and validate the interaction of Cdt2 with two other proteins that interact with the G9a/GLP and mediate their interaction with the DNA. Using interference RNA against Cdt2, we found that CRL4^Cdt2 does not regulate the half-life of the G9a/GLP protein complex, neither its subcellular localization. Because Cdt2 silencing causes re-replication and genomic instability, we also developed a cell line that does not express endogenous Cdt2 but harbors a doxycycline inducible Cdt2-Flag construct that allowed us to perform half-life experiments without affecting overall cellular homeostasis. Using different clones, we confirmed the results obtained with small interfering RNA. Finally, as mentioned before, it is well established that CRL4Cdt2 plays an important role in the regulation of the genotoxic stress response. Accordingly, recent reports indicate that G9a also intervenes in the regulation of the response to DNA damage. Therefore, we are currently studying whether the functional interaction between CRL4^Cdt2 and the G9a/GLP complex plays an important role in the modulation of the cellular response to different DNA damage agents. In this regard, we have obtained very encouraging preliminary results. Further studies are required to unveil the specific and intricate molecular mechanism of action of the CRL4^Cdt2/G9a axis and its role in the control of genomic stability. Fil: Enriqué Steinberg, Juliana Haydeé. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.

A pesar de los formidables avances logrados en el tratamiento, prevención y detección temprana de un gran número de cánceres, el desarrollo de procesos metastásicos en pacientes afectados con esta enfermedad continúa representando una reducción significativa en su supervivencia y calidad de vida restante. De hecho, la diseminación metastásica de un tumor primario a un segundo sitio es la causa principal de muertes por tumores sólidos. El desarrollo de metástasis requiere que las células tumorales completen una cascada de acontecimientos constituida por etapas bien definidas, que implican interacciones muy diversas entre las células tumorales y el organismo hospedador. El potencial invasivo de las células malignas depende de tres fenómenos: alteraciones en la adhesión celular, degradación proteolítica localizada de la matriz extracelular y movilidad de las células tumorales. Dicho potencial puede verse modificado por alteraciones genéticas en las células tumorales que podrían constituir posibles puntos de intervención terapéutica.La ubiquitinación representa una de las modificaciones post-traduccionales cuyo estudio ha despertado un creciente interés en el ámbito de la oncología molecular, debido a su gran potencial a nivel terapéutico en el tratamiento del cáncer. Prueba de esto último es el hecho que, en muchos casos, alteraciones en distintos componentes de la cascada de ubiquitinación están asociadas a la trasformación maligna de células tumorales y al desarrollo de procesos metastásicos. La cascada de ubiquitinación consiste en una red compleja de enzimas que median la unión covalente de múltiples unidades de ubiquitina a las proteínas, y representa una de las vías metabólicas más importantes que participa en el control de la proteostasis a nivel celular. Por lo tanto, el estudio de los mecanismos moleculares que rigen esta cascada enzimática, junto con el desarrollo de compuestos que inhiben o activen componentes específicos, posee un gran potencial a nivel terapéutico.En el contexto de lo señalado en los párrafos anteriores, el objetivo de esta tesis doctoral es identificar y caracterizar componentes de la cascada de ubiquitinación que representen potenciales nuevos blancos moleculares que puedan ser utilizados en futuros desarrollos y mejoras de las terapias antitumorales actuales. A tal fin se realizó un screen genético utilizando tecnología de ARN de interferencia para encontrar nuevos genes relacionados con el proceso de ubiquitinación que regularan positivamente el potencial migratorio de células tumorales. En particular se focalizó la atención en células derivadas de Cáncer de Mama triple Negativo (CMTN), una neoplasia maligna que posee un mal pronóstico, presenta alto riesgo de recurrencia metastásica y para la cual no se posee en la actualidad una terapia eficaz y específica. Mediante este procedimiento se identificó USP19, una enzima deubiquitinasa (DUB), como un nuevo regulador de los procesos de migración e invasión celular. Asimismo se validó, tanto in vitro, como así también en modelos animales in vivo, el rol que este gen cumple en el control de procesos de tumorigénesis resaltando su alto potencial como posible futuro punto de intervención terapéutico en el tratamiento del cáncer. Despite formidable advance in the prevention, early detection and treatment of a great number of cancers, the development of metastasis foci in patients suffering from this disease still represents a significant reduction in their survival and life quality. In fact, metastatic dissemination from a primary tumor to a secondary site is the principal cause of death from solid tumors. The invasive potential of malignant cells depends on three phenomena: alterations of cellular adhesion, localized proteolytic degradation of the extracellular matrix and tumor cell motility. The invasive ability is accomplished by a series of molecular and genetic alterations in tumor cells, which could represent putative therapeutic points of intervention. Due to its great potential as a new therapeutic option for the treatment of cancer, ubiquitination has attracted the attentions of the scientific community working on the molecular oncology field. This is based on the observations that several alterations in the levels of different ubiquitin-pathway components are associated with malignant transformation of tumor cells and the generation of metastatic processes. The Ubiquitination cascade consists of a complex network of enzymes that link ubiquitin units to proteins, and represents one of the most important pathways that regulate cellular proteostasis. Therefore, the study of the molecular mechanisms that regulate this enzymatic pathway, together with the development of new compounds that inhibit or activate specific components, may prove extremely important for pharmaceutical intervention in therapy. In relation to the hypothesis outlined in the previous paragraph, the focus of my PhD Thesis is to contribute to the development and improvement of anti-tumoral therapeutic strategies in cancer, by identifying and characterizing components of the Ubiquitination cascade that regulate tumor cell migration and invasion. To this end I performed a genetic screen using the shRNA technology using cells derived from Triple Negative Breast Cancers (TNBC), a malignant disease with poor prognosis, a high metastatic risk and for which there is no specific or effective treatment available. Using this strategy we identified USP19, a deubiquitinase enzyme (DUB), as a new regulator of cellular migration and invasion. Moreover, its role in tumorigenesis was validated both in vitro as well as in animal models in vivo, highlighting its potential as a possible future therapeutic intervention point for the treatment of cancer. Fil: Rossi, Fabiana Alejandra. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigación en Biomedicina de Buenos Aires - Instituto Partner de la Sociedad Max Planck; Argentina

Tesis (Doctor en Ciencias Químicas) - - Universidad Nacional de Córdoba. Facultad de Ciencias Químicas, 2014 Las modificaciones postraducción de proteínas son importantes para la regulación de la fisiología de la célula ya que contribuyen significativamente a la diversidad estructural y funcional de las proteínas. Una de estas modificaciones es la arginilación, la cual consiste en la unión covalente de un residuo de arginina en el extremo NH2 de proteínas aceptoras, específicamente sobre ácido aspártico, ácido glutámico, o cisteína. Esta reacción es catalizada por la enzima arginil-ARNt transferasa (Ate1) tanto en el citosol como en el núcleo celular. En nuestro laboratorio se ha establecido previamente que calreticulina (CRT), una proteína mayoritariamente residente del retículo endoplásmico (RE), se retrotransloca al citoplasma donde es uno de los sustratos de la arginilación. Además, se demostró que en condiciones de estrés que conducen a una disminución de los niveles intracelulares de Ca2+, CRT arginilada (R-CRT) se asocia a gránulos de estrés (GSs) que son complejos de ARNm y cuya función se correlaciona con una reducción selectiva de la traducción proteica. En el presente trabajo se describe la función de la arginilación de CRT en relación a la tasa de recambio ("turnover") de CRT citoplasmática, la cual modularía la estabilidad de la proteína. Además, se establece la vía de degradación de R-CRT en relación al rol que desempeña la arginilación. En este estudio se demuestra que tanto R-CRT como CRT se degradan por la vía proteosomal, aunque R-CRT tiene menor susceptibilidad que CRT a ser degradada por el proteosoma. Se determinó que la vida media de R-CRT es el doble que la de CRT citoplasmática sin arginilar. Cuando se sobre expresaron ambas proteínas en células knockout para la enzima Ate1 (células ATE1–/–), se confirmó que R-CRT es degradada de manera menos eficaz que CRT por el proteosoma. También, se encontró que CRT es degradada por una vía independiente de ubiquitina (Ub), mientras que la degradación de R-CRT es vía dependiente de Ub. En nuestro laboratorio recientemente se demostró que la arginilación de CRT promueve un alto grado de dimerización. En este sentido, la sobre expresión de una mutante de CRT (C146A-CRT-EGFP) que impide la formación de homodímeros, muestra niveles menores de R-CRT respecto de los encontrados cuando se sobre expresa CRT de tipo salvaje (wt), indicando que la dimerización de RCRT es en parte responsable de su estabilización. Por último, se encontró que tanto la expresión citoplasmática de R-CRT como la inhibición del proteosoma incrementan los niveles de R-CRT en la superficie celular. En su conjunto, estos resultados indican que una vez que CRT alcanza el citoplasma, la misma puede ser degradada por el proteosoma a través de una vía independiente de Ub o puede ser modificada por la enzima Ate1 formando R-CRT, la cual también es susceptible a la degradación proteosomal pero por vía dependiente de Ub, mostrando una vida media más larga que la CRT no modificada. Por otra parte, la estabilización de CRT por medio de su arginilación y dimerización, le permitiría a CRT participar en diferentes funciones en el citoplasma e incluso en otros compartimientos subcelulares a los que podría acceder desde el citoplasma. Fil: Goitea, Víctor Enrique. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas; Argentina. Fil: Hallak, Marta Elena. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Química Biológica; Argentina. Fil: Hallak, Marta Elena. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de Investigaciones en Química Biológica de Córdoba; Argentina. Fil: Alvarez, Cecilia Inés. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Bioquímica Clínica; Argentina. Fil: Alvarez, Cecilia Inés. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina. Fil: Pérez, Mariela Fernanda. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Farmacología; Argentina. Fil: Pérez, Mariela Fernanda. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Farmacología Experimental de Córdoba; Argentina. Fil: Maccioni, Hugo José. Fernando Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Química Biológica; Argentina. Fil: Maccioni, Hugo José. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de Investigaciones en Química Biológica de Córdoba; Argentina. Fil: Rossi, Mario. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Medicina Trasnacional; Argentina.

Introduction: Treatment of elderly patients with small cell lung cancer (SCLC) is based on scanty evidence. Methods: Patients with extensive SCLC, age >70 years, and performance status 0-2 were eligible for a study looking for optimal two-drug combination of gemcitabine (Gem) with vinorelbine (Vin), etoposide (Eto), cisplatin (Cis), or carboplatin (Car). Gemcitabine dose was the same (1000 mg/m2, days 1-8) in all combinations. A two-stage minimax flexible design for response was applied to GemVin combination (Vin 25 mg/m2, days 1-8). For GemCar, GemCis, GemEto, a phase I-II Bayesian design was applied, looking for the optimal dose of the partner drugs. Objective response rate ≥60% and unacceptable toxicity ≤25% were required to define a combination worthy of further studies. Results: Median age of 78 eligible patients was 74 years. GemVin produced a 36.7% objective response rate. GemEto and GemCis arms were found not sufficiently active. GemCar produced 16 responses (14 with area under the curve [AUC] 3.5 and 2 with AUC 4.0) in 26 patients (61.5%) and 6 cases of unacceptable toxicity (3 at each Car dose). Conclusions: In elderly patients with extensive SCLC, GemVin, GemEto, and GemCis are not enough active and do not merit further studies. Gem plus Car might deserve further attention. © 2011 by the International Association for the Study of Lung Cancer.

L’Italia contemporanea, come qualsiasi altro paese industrialmente avanzato, è una società profondamente “mediata” in ogni suo sistema e processo, tanto che per la gran parte della popolazione i mezzi di comunicazione sociale risultano essere di gran lunga la fonte di idee, conoscenze e giudizi. Quindi, anche l’immagine della Chiesa oggi si forma in misura crescente a partire dall’“incorniciamento” massmediale. In questo saggio ho voluto offrire qualche spunto di riflessione sul rapporto tra media e religione. Si tratta di un tema finora poco coltivato dai sociologi appartenenti a entrambe le specialità disciplinari, ovvero i massmediologi e gli studiosi dei fenomeni religiosi . Dapprima ho richiamato in estrema sintesi alcuni aspetti della breve storia dei rapporti tra televisione e Chiesa cattolica in Italia (n.2). Poi, impiegando il concetto di de-secolarizzazione, ho offerto una proposta interpretativa del successo di audience che ottengono i grandi eventi religiosi attuali, dalle cerimonie giubilari alle Giornate mondiali della Gioventù (n. 3). Ho cercato pure di mettere in evidenza gli aspetti problematici di questi successi di audience, accennando a tre dilemmi che essi pongono a preti, pastori e leader religiosi (n. 4). Infine ho avanzato una riflessione sulle possibili conseguenze di questo intensificato rapporto tra neo-televisione e religione, che ho accostato al tentativo, effettuato all’alba della società moderna da Immanuel Kant (1793), di ridurre la religione nei limiti della ragion pura. Suggerirò pertanto l’ipotesi che i processi socio-culturali attuali, che stanno trasformando la modernità in una società “post”-moderna (n.5), stiano contribuendo pure a plasmare un inedito modello di religiosità, che trova nella neo-televisione un potente canale di diffusione. Nella conclusione accennerò ai paradossi che il tentativo attuale di ridurre la religione nei limiti della neo-televisione comporta, sia per i media, sia per la stessa Chiesa.

The main objective was to show that the acoustic tomography constitutes a new method to investigate the main hydrodynamical processes of the lake of Geneva. The work is based of the various related fields to the tomography, namely : acoustic wave propagation, signal processing and physical limnology. The development of a tomographic system was carried out so as to study the dynamics of the Great Lake by the analysis of the propagation along its small axis. This work is based on modelling of the sound propagation and its systematic comparison with experimental data. The constitution of a temperature profiles calendar is created starting from four orthogonal empirical functions constituting a fundamental information for the resolution of the tomographic problem. The modelling of the thermal destratification and of internal stationnary waves effects on the propagation validate winter measurements, which are correlated with the weather data. It is established that the qualification of the major processes controlling hydrodynamics (thermal stratification, internal waves) is possible by the analysis of sound travel times between two sites close to the banks. The main part of this work constitutes a reference for the adaptation of oceanic tomography to the case of great lakes. It suggests solutions for a best comprehension of the major processes during their phase of thermal destratification.

Noise radiated by different industrial structures that surround us in daily life are more and more considered as environmental pollution. Standards defining a tolerable sound level for each of these noise sources are regularly called into question and respecting them becomes an additional constraint for manufacturers. The last decades have seen the increasing development of means used to fight these noise disturbances. The wide diversity of noises perceived as harmful has contributed to the progressive increase in specificity and efficiency of solutions proposed to reduce the disturbances. For some applications, passive solutions, based on the use of materials capable of absorbing or deviating acoustic or vibratory waves, have progressively been replaced by "active" solutions, based on the generation of an acoustic wave of opposite phase to the disturbing one radiated by the noise source. Power transformers are sources for which passive solutions (anti-noise walls) are usually expensive and not very efficient, particularly at low frequency. Furthermore, characteristics of noise radiated by transformers (low frequency tone noise) are such that they are particularly well suited for the implementation of an active solution. Typically, an active control system dedicated to transformers (feedforward) is composed of actuators, used to generate the anti-noise and usually located near the tank, sensors, used to measure the attenuation obtained and to provide a reference signal, and a controller used to drive the actuators as a function of the information collected by the sensors. When the sensors are microphones, they are usually moved away from the noise source, in such a way that they pick up acoustic pressure that is representative of the noise propagated far away. In the vicinity of the source, local acoustic phenomena can occur which are not propagated far away. A microphone located near the noise source would therefore pick up an acoustic pressure that did not necessarily represent the one that effectively exists far away, the area where we are in fact seeking to reduce the noise. These phenomena, frequently grouped under the term "nearfield" tend to decrease the performance of the control system, owing to the fact that the controller seeks in this case to reduce an acoustic pressure which is not representative of the noise to be reduced. In practice, the significant amount of wiring required as a result of the positioning of the microphones in the far field, has a non-negligible effect on the cost of the system. The possibility of bringing the sensors closer to the source is sufficiently advantageous to envisage to studying the feasibility and the resulting consequences. The present approach consists in representing the primary field radiated by a vibrating structure in terms of a set of "acoustic radiation modes". The use of radiation modes to characterise the behaviour of a structure has received increasing attention since the beginning of 90's, especially for active control applications. Usually, this approach consists in representing the radiated power in terms of a set of surface velocity distributions, called radiation modes, that have the property of radiating independently of each other. Radiation modes result from diagonalization of a discrete expression of the radiation operator. We propose here to study the consequences on the radiation modes of a structure from bringing the microphones closer to it. We will study how the acoustic field varies with the distance and how this can be used to obtain a model, the complexity of which is adapted to the observation distance.

The assumptions of linearity and autonomy assumed in circuit theory are known to be respected only partially by electroacoustic transducers. In particular, the dynamics range of the latter is limited by the audible nonlinear effects that they are causing. In the domain of active noise control, the distortion products limit noise reduction performance. The present thesis work stems from characterization of these observations. We want to design a real-time system compensating the nonlinearities of electroacoustic devices. The first part of this report concerns the nonlinearity effects. It is shown that the use of classical characterization methods of an electroacoustic device (harmonic distortion, intermodulation, frequency difference ...) is limited. Hence, they can not be used to determine the nonlinearity laws themselves, but rather only their effects for arbitrary excitations. First, a method based on multitone harmonic excitations has been proposed and validated. It has been applied for the characterization of loudspeaker prototypes using several different technologies, which are used for active noise reduction in an aircraft turboreactor. The second part of this work addresses the elaboration and validation of a nonlinearity effect compensation method. This method is based on the description of the nonlinearities by the Volterra series. For this, we need to place an upstream system, characterized by the inverse nonlinearity law of the loudspeaker system. After having determined precisely the Volterra kernels of the system to be characterized, the kernels of the upstream compensation system are determined by assuming that their cascade obeys to a linear law. For this purpose, a kernel measurement method in the frequency domain has been developed, validated and tested. Since we are concerned with loudspeakers, we took their flying time into account. The compensation method has been validated by computing the simulated response of the compensation circuit. Resulting analog signals have then been applied to the loudspeaker. Measured performances fulfill the expectations. In the last part, the compensation method has been applied in a real-time Digital Signal Processing) DSP controller, which allowed to realize a demonstrator to the implemented for future industrial applications.

This work was motivated by the increasing need for acoustic localization systems. The various localization systems that were implemented during this PhD include localization of snow avalanches, artillery and supersonic aircraft in the infrasound domain, the localization of helicopters, civilian aircraft, speakers and auditorium reflections in the audio domain and the localization of chirps in the underwater ultrasound domain. The "goniometer" is defined as an instrument that measures angles. An "acoustic goniometer" is therefore a system that measures the direction of arrival (DOA) of sounds, and thus estimates the source direction. A goniometer is made up of an antenna, composed of several sensors arranged in a particular geometry, and a calculation algorithm. The successive implementations were designed around a common framework, based on a two-step spatio-temporal process. The temporal step tackles the problem of the Time Delay Estimation along the antenna baselines, whereas the second step introduces the antenna geometry, in order to estimate the Direction of Arrival per se. The multi-sources case, as well as the outlier's rejection, is assured by a detection module, which uses the temporal and spatial properties of the propagation model. The performances of the TDE and the localization are studied as a function of every relevant parameter, in order to determine the optimal antenna to run the two-step process. The antenna design rules concern its geometry, its size and its orientation. The results presented in the applications chapter give a realistic idea of the goniometry capacities. Its performances are largely competitive to those of other techniques. Up to now, the goniometry developed during this work, fulfilled all prior requirements. Moreover, the goniometry appeared to be, in many cases, in advance with regards to technological tools such as the sound pick-up, the CPU implementation or installation constraints. The advice that could be given, when tackling a new antenna design, is firstly to visualize both spatial and temporal properties of the propagating waves and of the perturbating phenomena, and secondly to compare them to the goniometer characteristics. This work has demonstrated that the best performances were achieved for the goniometry of a unique stationary compact source generating broadband low pass signals in a homogenous medium without wind and noise, performed with a wide symmetrical broad-side antenna.

The aim of this work was to analyze the global behavior of a loudspeaker exciting a room in the frequency band of its first modes, for the purpose of active control applications. First, the loudspeaker in free field was studied. The characterization of a loudspeaker on the base of equivalent circuits has been established, showing the preponderant importance of the load impedance, determined by near field measurements. Then, the steady state has been modeled and the study has been set on the characterization of the wall impedance, which determines the eigenfrequencies and the amplitude of their modes, as well as charge impedance. The latter which modifies the volume velocity compared with the one in free field, has been characterized. The previous results enable the precise computation of the pressure field in a closed space and excited by a loudspeaker in steady state, according to the wall impedance. For active control purposes, transitory sounds are particularly important, therefore the behavior of a sound field in a room excited by several parameterized sounds has been studied in the time domain. The room response to the source activation could therefore be modeled. This response consists of a free and a transitory state, both of which are qualified through coherent assumptions and observations. Through simulation and systematic experimentation, the loudspeaker-room system has been characterized for a stationary as well as for a transitory sound, revealing the constraints affecting modal active control. Many experiments showed the efficiency of modal active noise control. Observations presented the importance of low frequencies in the annoyance of airplane noise inside rooms. Directives have been given to install active noise reduction system. The main part of this work constitutes an electro acoustical knowledge basis to perform modal active noise control.

Within the framework of an outdoor active noise control project, a need arose, namely to establish whether electrodynamic loudspeakers are likely to be affected by the primary noise or by the interactions between them. The aim of this thesis is therefore to provide computation and measurement methods allowing to predict whether the effects of an incident sound field on a loudspeaker have to be taken into account. The study comprises two main parts involving modelling, theory and calculations for the first part, and experimental validations in an anechoic chamber for the second one. The equivalent circuit modelling of an electrodynamic loudspeaker shows that its behaviour can be completely determined from its input impedance. The thesis starts with the reflection that the modifications in loudspeaker behaviour due to the presence of an incident sound pressure applied on its radiating membrane could then also be analysed in the same way. The chosen process then consists in analysing the loudspeaker modifications in behaviour, no longer as variations of its radiation impedance, but as variations of its volume velocity and input impedance. The latter, which is located at the electrical loudspeaker terminals, offers the advantage of being easily measurable. Within the scope of this thesis, the loudspeakers are assumed to behave like flat rigid pistons. Based on Thiele and Small parameters and using Rayleigh's surface integral and the unified and geometrical theories of diffraction, the calculations enable input impedance, volume velocity, near and far field sound pressure, as well as medium reaction force and radiation impedance to be obtained for each loudspeaker. Taking into account interaction effects, they also enable the modifications of all these quantities in modulus and phase to be predicted. A discrete approach is chosen in order to minimize the computation time. The calculations were however fine tuned in such a way as to ensure sufficient accuracy in relation to measurement uncertainties. In order to evaluate the orders of magnitude of the modifications in loudspeaker behaviour, some preliminary calculations are first carried out in the simple case of two closed-box loudspeakers mounted in the same infinite baffle. This part also leads to understand how input impedance and volume velocity modifications vary according to excitation ratio, excitation difference of phase and distance between piston centres. Then and in order to get closer to realistic configurations, the calculations are carried out in the cases of two adjacent and distant closed-box loudspeakers. A test bench enables then the effects of an incident sound field on a closed-box loudspeaker to be measured. The configuration is chosen in order to eliminate any diffraction and significant mutual effects likely to distort the results. The aim of this first experiment is to highlight every potential measurement difficulty in order to determine the measurement setup, as well as to validate the choice of the measured quantities (input impedance and volume velocity). Once the orders of magnitude of the modifications in loudspeaker behaviour are evaluated, the study focuses on three different loudspeaker configurations beginning with the most simple case of two closed-box systems mounted in a baffle, and ending with most realistic ones, corresponding to the configurations of loudspeakers mounted in an array (two adjacent and distant closed-box systems). It is worth noting here that the measurement accuracy of the Thiele and Small's parameters plays an essential role in this study. The results of the measurements carried out in each configuration are finally compared to the theoretical predictions, enabling calculation methods to be validated.