‘We’re All Mad Here’: Alienation, Madness, and Crafting Tom Waits

Tom Waits, through his poetry, his poetic and public personae, has become the father of the desperate failures of society, those who lay down and fill the background with disillusionment. No-direction-homers flock together and become the majority of Waits’ main characters. As an artist, he gives a voice and a name to those who, otherwise, would remain invisible, endowing them with corporeality. Waits, through the projection of his public persona, illumines the lives of the weak, who strive to survive in a world that has always fed upon those below. There is something honourable about the people who struggle the most, trying to find their path in the darkest of places, and Waits, through his career as an entertainer, has always prioritised his respect for these people, praising their many faults and poor decisions, merging them with the tormented collective and thus becoming one with their sadness and horror. This paper will focus on how Tom Waits constructs his personae through an identification with the disappointments of society: the underdog, and, more particularly, the alcoholic underdog. I intend to focus mainly on the lyrical content of his albums Rain Dogs and Small Change, together with their respective representations in other art forms, specifically interviews, lives, artistry, etc. This section will also include Tom Waits’ depiction of some characters as grotesques, as they form the limits of societal acceptance. In the last section, I will examine the presence and construction of these grotesques in his album Alice (2002), while comparing the lyrical content to its other cultural manifestations

Influence de la Transition Epithélio-Mésenchymateuse sur la réponse T cytotoxique anti-tumorale

The anti-tumor immunology and immunotherapy have recently undergone major breakthroughs, with the identification of immune surveillance process and the development of several vaccine approaches. However, the fact remains that the induction of an antitumor immune response is still not effective enough. Certainly, the antitumor cytotoxic response is a dynamic and interactive phenomenon, involving cytotoxic effectors and tumor targets, but its effectiveness is considerably influenced by the tumor microenvironment and its plasticity. Recent studies support the importance of taking into account the tumor susceptibility to lysis by anti-tumor cytotoxic effectors, notably Cytotoxic T Lymphocytes (CTLs), especially in a context of cellular plasticity. On the grounds of these studies, this research aims at understanding the role of Epithelial to Mesenchymal Transition (EMT) in the susceptibility of tumor cells to CTLs mediated lysis in different models of breast cell carcinoma. Our results reveal that EMT is able to induce a decrease in the susceptibility of mesenchymal cells to specific lysis. It calls therefore multiple actors. First, in both study models, it turns out that the EMT is able to downregulate the expression of HLA-A2 molecule. Then, in the first experimental model, we show that EMT induces an alteration of signalling at the immunological synapse. Moreover, the regulator of autophagy, Beclin 1, plays a crucial role in the induction of reduced susceptibility to lysis by T-CD8+ lymphocytes following induction of EMT. In the second experimental model, we show that the mechanisms used by EMT to regulate the susceptibility of mesenchymal cells to lysis by CTLs involve the induction of the transcription factor inducing cancer stem cells properties, KLF4, as well as the downregulation of miR-7 expression. Together, these results shed light on new mechanisms used by malignant tumor cells to escape to lysis by T-CD8+ lymphocytes following the induction of EMT. Thus, this study advocates the importance of targeting transcription factors, which are inducers of EMT and responsible for cellular plasticity, in order to neutralize their function. These insights may prove useful for the development of new strategies aimed at better controlling the escape of invasive tumor cells to specific lysis, and ultimately ensuring a more effective immunotherapy against cancer.L’immunologie anti-tumorale et l’immunothérapie ont connu dernièrement de grandes avancées avec la mise en évidence du processus d’immuno-surveillance et le développement de plusieurs approches vaccinales. Il n’en demeure pas moins que l’induction d’une réponse immunitaire anti-tumorale se traduit peu par l’éradication de la tumeur. Comme phénomène dynamique et interactif, la réponse cytotoxique anti-tumorale implique les effecteurs cytotoxiques et les cibles tumorales; pourtant, le microenvironnement tumoral et sa plasticité influent largement sur l’efficacité de celle-là. Avec l’appui de récentes données expérimentales, il apparaît crucial de prendre en compte la susceptibilité tumorale à la lyse par les effecteurs cytotoxiques anti-tumoraux, notamment les lymphocytes T cytotoxiques (CTLs), et plus particulièrement dans un contexte de plasticité cellulaire. Ainsi, le principal objectif de mes travaux de thèse est de saisir le rôle de la Transition Épithélio-Mésenchymateuse (EMT) dans la susceptibilité des cellules tumorales à la lyse par les CTLs dans des modèles cellulaires de cancer du sein. Nos résultats montrent que l’EMT est capable d’induire une diminution de la susceptibilité des cellules mésenchymateuses à la lyse spécifique. Elle engage de ce fait de multiples acteurs. Tout d’abord, dans les deux modèles d’étude, il s’avère que l’EMT est capable de réguler négativement l’expression de la molécule HLA-A2. Ensuite, dans le premier modèle expérimental, nous avons établi que l’EMT induit une altération de la signalisation au niveau de la synapse immunologique. De plus, le régulateur de l’autophagie, Becline 1, joue un rôle crucial dans l’induction de la diminution de la sensibilité à la lyse par les lymphocytes T-CD8+ suite à l’induction de l’EMT. Dans le deuxième modèle d’étude, le mécanisme mis en jeu par l’EMT pour réguler la susceptibilité des cellules mésenchymateuses à la lyse par les CTLs se manifeste dans l’induction du facteur de transcription inducteur des propriétés de cellules souches cancéreuses, le KLF4 ainsi que via la régulation négative de l’expression du miR-7. Ensemble, ces résultats élucident de nouveaux mécanismes d’échappement des cellules tumorales malignes à la lyse par les lymphocytes T-CD8+ suite à l’induction de l’EMT. Cette étude soutient ainsi l’importance du ciblage des facteurs de transcription inducteurs de l’EMT et responsables de la plasticité cellulaire afin de neutraliser leur fonction. Cela pourrait aider à construire une nouvelle stratégie pour mieux contrôler l’échappement des cellules tumorales invasives à la lyse spécifique et in fine pour garantir une immunothérapie plus efficace contre le cancer

Islam and Laicism

URL del artículo en la web de la Revista: https://www.upo.es/revistas/index.php/ripp/article/view/1542El Laicismo en el Islam ha separado a musulmanes sunníes y shíies, a los fundamentalistas de los liberales desde hace más de una centuria, como se ha evidenciado en etiquetas como ladiniya e ilmaniya. Intelectuales marroquíes de izquierda se han adentrado periódicamente en este debate. Pero mientras los europeos tienden a entender este conflicto en las comunidades musulmanas como una confrontación entre laicismo y teocracia, en el seno de estas comunidades el problema es entendido como el conflicto de tradición versus modernidad. En realidad, el laicismo es una invención religiosa que muchos pensadores creen compatible con principios islámicos. La comunidad musulmana española está compuesta de pueblos de muy diferentes países, donde el Islam es la única religión, y para ellos el nuevo contexto europeo está generando nuevas vías para vivir su fe religiosa. Después del 11-M, sin embargo, algunos columnistas de prensa y escritores españoles han decidido estigmatizar al Islam, y muchos problemas sociales y económicos son interpretados como culturales o religiosos. España tiene un importante rol que desarrollar en este debate.Laicism in Islam has divided Sunni Muslims from Shiites and fundamentalists from liberals for more than a century, as evidenced in labels such as ladiniya, ilmaniya. Moroccan leftist intellectuals have periodically entered the dabate. But, while europeans tend to understand conflicts within european muslim communities as a confrontation between laicism and teocracy, within those communities the problem is understood as that of tradition vs. modernity. In fact, laicism is a religious invention that many thinkers deem compatible with Islamic principles. The Spanish Muslim community is composed by people from many different countries where Islam is the only religion, and their new European context is generating new ways of living their religious faith. After 11-M, however, some spanish journalists and writers have taken to stigmatize Islam, and many social and economic problems are interpreted as cultural or religious ones. Spain has an important role to play in the debate.Universidad Pablo de Olavid

Islam y Laicidad

El Laicismo en el Islam ha separado a musulmanes sunníes y shíies, a los fundamentalistas de los liberales desde hace más de una centuria, como se ha evidenciado en etiquetas como ladiniya e ilmaniya. Intelectuales marroquíes de izquierda se han adentrado periódicamente en este debate. Pero mientras los europeos tienden a entender este conflicto en las comunidades musulmanas como una confrontación entre laicismo y teocracia, en el seno de estas comunidades el problema es entendido como el conflicto de tradición versus modernidad. En realidad, el laicismo es una invención religiosa que muchos pensadores creen compatible con principios islámicos. La comunidad musulmana española está compuesta de pueblos de muy diferentes países, donde el Islam es la única religión, y para ellos el nuevo contexto europeo está generando nuevas vías para vivir su fe religiosa. Después del 11-M, sin embargo, algunos columnistas de prensa y escritores españoles han decidido estigmatizar al Islam, y muchos problemas sociales y económicos son interpretados como culturales o religiosos. España tiene un importante rol que desarrollar en este debate.------------------------------------------------------------------Laicism in Islam has divided Sunni Muslims from Shiites and fundamentalists from liberals for more than a century, as evidenced in labels such as ladiniya, ilmaniya. Moroccan leftist intellectuals have periodically entered the dabate. But, while europeans tend to understand conflicts within european muslim communities as a confrontation between laicism and teocracy, within those communities the problem is understood as that of tradition vs. modernity. In fact, laicism is a religious invention that many thinkers deem compatible with Islamic principles. The Spanish Muslim community is composed by people from many different countries where Islam is the only religion, and their new European context is generating new ways of living their religious faith. After 11-M, however, some spanish journalists and writers have taken to stigmatize Islam, and many social and economic problems are interpreted as cultural or religious ones. Spain has an important role to play in the debate

ANALYSE DU COMPORTEMENT DU HANDOVER VERTICAL SELON UNE VARIETE DE PROTOCOLES DE TRANSPORT

Ce travail s’inscrit dans un projet visant à assurer une continuité de service pour une application de Voix IP (Internet Protocol) lors de la traversée de deux réseaux mobiles différents. Dans cet article nous nous intéressons à évaluer l’utilisation de différents protocoles de transport TCP (Transport Control Protocol) : TCP New-Reno et TCP Vegas, en considérant différents paramètres liés à la QoS (Quality of Service). Cette évaluation s’effectue dans un contexte de mobilité d’un utilisateur entre deux réseaux mobiles hétérogènes (Wifi et Wimax). La plateforme NS2 (Network Simulator) sera utilisée pour effectuer les mesures nécessaires à cette évaluation de protocoles

Cytokeratin 18 expression pattern correlates with renal cell carcinoma progression: Relationship with Snail

Renal cell carcinoma (RCC) is the most common type of kidney cancer and recent developments in the molecular biology of RCC have identified multiple pathways associated with the development of this cancer. This study aimed at analyzing the expression pattern of cytokeratin 18 (CK18) in RCC patients and its prognostic relevance. We quantified CK18 mRNA expression and protein using real-time reverse transcription quantitative polymerase chain reaction (RT-QPCR) and immunohistochemistry, respectively, in paired tumor and non-tumor samples from 42 patients. Our data indicate that CK18 mRNA and proteins levels increased with advanced stage and grade of the disease. Using primary (RCC5) and metastatic renal cell carcinoma (RCC5 met) cell lines, we demonstrated that CK18 expression was 5-fold higher in the metastatic as compared to the primary RCC cell line and correlated with a migratory phenotype characterized by a distinct elongated morphology as revealed by Phalloidin staining. In addition, RCC5 met cells displayed an increased capacity to attach to fibronectin and collagen which was lost following CK18 knock-down. Our data also indicate that the expression of CK18 was associated with increased Snail expression which correlated positively with advanced disease in RCC patients. The present findings suggest that CK18 may play an important role in the progression of RCC and it may be used as a new predictor for RCC