Dynamic, Large-Scale Profiling of Transcription Factor Activity from Live Cells in 3D Culture

phenotypes. Taken together, our objective was to develop cellular arrays for dynamic, large-scale quantification of TF activity as cells organized into spherical structures within 3D culture.TF-specific and normalization reporter constructs were delivered in parallel to a cellular array containing a well-established breast cancer cell line cultured in Matrigel. Bioluminescence imaging provided a rapid, non-invasive, and sensitive method to quantify luciferase levels, and was applied repeatedly on each sample to monitor dynamic activity. Arrays measuring 28 TFs identified up to 19 active, with 13 factors changing significantly over time. Stimulation of cells with β-estradiol or activin A resulted in differential TF activity profiles evolving from initial stimulation of the ligand. Many TFs changed as expected based on previous reports, yet arrays were able to replicate these results in a single experiment. Additionally, arrays identified TFs that had not previously been linked with activin A.This system provides a method for large-scale, non-invasive, and dynamic quantification of signaling pathway activity as cells organize into structures. The arrays may find utility for investigating mechanisms regulating normal and abnormal tissue growth, biomaterial design, or as a platform for screening therapeutics

Effects of Anacetrapib in Patients with Atherosclerotic Vascular Disease

BACKGROUND: Patients with atherosclerotic vascular disease remain at high risk for cardiovascular events despite effective statin-based treatment of low-density lipoprotein (LDL) cholesterol levels. The inhibition of cholesteryl ester transfer protein (CETP) by anacetrapib reduces LDL cholesterol levels and increases high-density lipoprotein (HDL) cholesterol levels. However, trials of other CETP inhibitors have shown neutral or adverse effects on cardiovascular outcomes. METHODS: We conducted a randomized, double-blind, placebo-controlled trial involving 30,449 adults with atherosclerotic vascular disease who were receiving intensive atorvastatin therapy and who had a mean LDL cholesterol level of 61 mg per deciliter (1.58 mmol per liter), a mean non-HDL cholesterol level of 92 mg per deciliter (2.38 mmol per liter), and a mean HDL cholesterol level of 40 mg per deciliter (1.03 mmol per liter). The patients were assigned to receive either 100 mg of anacetrapib once daily (15,225 patients) or matching placebo (15,224 patients). The primary outcome was the first major coronary event, a composite of coronary death, myocardial infarction, or coronary revascularization. RESULTS: During the median follow-up period of 4.1 years, the primary outcome occurred in significantly fewer patients in the anacetrapib group than in the placebo group (1640 of 15,225 patients [10.8%] vs. 1803 of 15,224 patients [11.8%]; rate ratio, 0.91; 95% confidence interval, 0.85 to 0.97; P=0.004). The relative difference in risk was similar across multiple prespecified subgroups. At the trial midpoint, the mean level of HDL cholesterol was higher by 43 mg per deciliter (1.12 mmol per liter) in the anacetrapib group than in the placebo group (a relative difference of 104%), and the mean level of non-HDL cholesterol was lower by 17 mg per deciliter (0.44 mmol per liter), a relative difference of -18%. There were no significant between-group differences in the risk of death, cancer, or other serious adverse events. CONCLUSIONS: Among patients with atherosclerotic vascular disease who were receiving intensive statin therapy, the use of anacetrapib resulted in a lower incidence of major coronary events than the use of placebo. (Funded by Merck and others; Current Controlled Trials number, ISRCTN48678192 ; ClinicalTrials.gov number, NCT01252953 ; and EudraCT number, 2010-023467-18 .)

Historia e historización, ficción y metaficción en Los surcos del azar, de Paco Roca

Cet article analyse, d’une part, les procédés graphiques et narratifs par lesquels Los surcos del azar, de Paco Roca, se voit légitimé comme récit véridique et fidèle à l’histoire et, d’autre part, les techniques qui le désignent, a contrario, comme un artefact et une recréation fictive. À partir de ce contrepoint entre volonté de témoigner et revendication d’un artifice assumé, il propose une réflexion sur les apports et les spécificités de la mémoire, du discours et du genre de la BD dans l’écriture de l’Histoire.This article analyzes, on the one hand, the graphic and narrative processes by which Los surcos del azar, by Paco Roca, sees itself legitimized as a true story and faithful to history and, on the other hand, the techniques which designate it, a contrario, like an artifact and a fictional rewriting. From this counterpoint between the desire to testify and the claim of an assumed artifice, he offers a reflection on the contributions and specificities of memory, discourse and the literary genre of comics in the writing of History.Este artículo analiza, por una parte, los procedimientos tanto gráficos como narrativos que legitiman Los surcos del azar de Paco Roca como relato verídico y fiel a la historia y, por otra parte, las técnicas que lo señalan, a contrario, como artefacto y recreación ficcional. A partir de este contrapunto entre voluntad testimonial y reivindicación de un artificio asumido, se reflexiona sobre los aportes y especificidades de la memoria, del discurso y del género del cómic a la hora de escribir la Historia

L'imaginaire visuel de la guerre civile espagnole: "36-39. Les Temps Mauvais", de Carlos Giménez, ou comment tourner la page sans oublier

Cette communication analyse les dispositifs de mise en récit de la guerre civile espagnole dans la bande dessinée, en s'attachant aux rapports entre progression et stase et aux enjeux de ces stratégies, dans la problématique d'un nécessaire dépassement lié aux exigences d'une transmission de la mémoire

Les Googlegramas de J.Fontcuberta sur les photographies de guerre de A.Centelles: un travail contre l'oubli, la banalisation et la muséification de la violence

International audienceCette communication analyse le dispositif des Googlegramas utilisé par le photographe Joan Fontcuberta , qui retravaille certains clichés de la guerre civile du reporter de guerre Agustí Centelles, et s'interroge sur le rapport à la violence institué par ces images revisitées à l'ère digitale

Esthétique du fragment vs construction d'un récit: la mémoire de la guerre civile dans la bande dessinée. Quelques réflexions sur "Malos Tiempos 1936-39" de Carlos Giménez

Cette communication analyse les enjeux de la narration séquentielle propre à la Bande Dessinée dans la cadre d'une relecture d'un des antagonismes majeurs de l'Espagne du XXè siècle : la guerre civil

Ors, éclairages, fonds lumineux: réflexions sur quelques effets de lumière chez Goya

International audienceL'article s'intéresse aux emplois et significations de la lumière, du contre-jour, des fonds abstraits et des touches d'or dans les tableaux de Francisco de Goy

La mise en scène du Madrid populaire dans l'oeuvre de Carlos Giménez.Eléments de réflexion

Cette communication analyse les représentations du Madrid populaire dans la bande dessinée "Barrio" de Carlos Giméne

Une expérience de théâtre historique : Fermín Galán

Fermín Galán es una obra de propaganda republicana. Plantea la difícil articulación entre la vanguardia estética y la vanguardia política. Alberti recurre al romance, clave de la arquitectura temporal compleja de la obra. Valiéndose de elementos tradicionales, funda la legitimidad del nuevo héroe. El juego de los tiempos verbales y la alternancia entre la narración y la representación que estructura toda la obra son los fundamentos de un teatro dentro del teatro que invita al espectador a desempeñar un papel activ

Au sujet d'un travail inédit de García Lorca: la version lorquienne de La Dama Boba de Lope de Vega

Phocas-Sabbah Jacqueline. Au sujet d'un travail inédit de García Lorca: la version lorquienne de La Dama Boba de Lope de Vega. In: Mélanges de la Casa de Velázquez, tome 29-3, 1993. Epoque contemporaine. pp. 63-95