A Large-Area RPC Detector for Muography

A muon telescope equipped with four Resistive Plate Chambers of 2 m$^{2}$ per plane was tested with the muon scattering tomography technique. The telescope was operated during several hours with high atomic number materials located at its center with two detector planes on each side. With an intrinsic efficiency above 98%, spatial resolution around 1 cm and detector planes spaced by 45 cm, it was possible to identify the presence of a 5 cm thick tungsten block in 10 minutes of acquisition. The results obtained after five hours of acquisition are also presented in this communication

Advances Towards a Large-Area, Ultra-Low-Gas-Consumption RPC Detector

Large Resistive Plate Chamber systems have their roots in High Energy Physics experiments at the European Organization for Nuclear Research: ATLAS, CMS and ALICE, where hundreds of square meters of both trigger and timing RPCs have been deployed. These devices operate with complex gas systems, equipped with re-circulation and purification units, which require a fresh gas supply of the order of 6 cm$^{3}$/min/m$^{2}$, creating logistical, technical and financial problems. In this communication, we present a new concept in the construction of RPCs which allowed us to operate a detector at ultra-low gas flow regime. With this new approach, the glass stack is encapsulated in a tight plastic box made of polypropylene, which presents excellent water vapor blocking properties as well as a good protection against atmospheric gases.Comment: submission of the proceedings for the 15th PISA conference PM202

Anchoring of 10-phenylphenothiazine to mesoporous silica materials: A water compatible organic photocatalyst for the degradation of pollutants

The application of organic photocatalysts towards the oxidation of pollutants in water is hampered by different limitations such as their insolubility in the media. Herein, we report that the grafting of a photo-organocatalyst into mesoporous silica materials is an ideal approach to obtain effective catalysts. Thereby, the photocatalyst 10-phenylphenothiazine (PTH) was easily anchored into three different mesoporous silica-based materials (MSN, MSU-2 and SBA-15) with different particle sizes and pore sizes through an amide bond formation. The materials were characterized using IR analysis, solid-state X-ray diffraction, porosity and microscopy (SEM and TEM) techniques, showing that PTH is immobilized inside the pores of the materials and its optical properties are maintained after the anchoring. Although homogeneous PTH was inactive in water media, the three photocatalytic materials were active for the degradation of pollutants. SBA-15-AP-PTH exhibited the highest catalytic performance towards the degradation of acetaminophen and diclofenac under solar irradiation, finding in this manner a new strategy for the decontamination of pollutantsThis work was financially supported by the European Research Council (ERC-CoG, No. 647550), Spanish Government (No. RTI2018- 095038-B-I00), and Spanish State Research Agency (No. PID2019-106186RB-I00/AEI/10.13039/ 501100011033

Adaptación de metodologías activas a la docencia a través del campus virtual en asignaturas del área de educación artística de Grado y Máster en la Facultad de Bellas Artes

El proyecto Adaptación de metodologías activas a la docencia a través del campus virtual en asignaturas del área de educación artística de grado y máster en la Facultad de Bellas Artes que presentamos para la convocatoria INNOVA-Docencia 2020-2021, se enmarca en la línea de trabajos en innovación docente de un equipo de profesores de la sección de Formación Artística del Departamento de Escultura y Formación Artística de la Facultad de Bellas Artes. Consiste en el diseño, implementación y evaluación de actividades implementadas a través del Campus Virtual mediante estrategias de aprendizaje de participación activa (metodologías activas) con alumnos de Grado y Máster. Durante los cursos académicos 2018-19 y 2019-20, habíamos estado desarrollando actividades basadas en metodologías activas, fomentando el aprendizaje por descubrimiento, el trabajo cooperativo, el conocimiento significativo o los hábitos de investigación. Partiendo de esta experiencia, queríamos comenzar a probar la viabilidad de estas metodologías en el Campus virtual, para poder ofrecer este tipo de aprendizaje en este entorno durante un curso en el que se preveía que la enseñanza iba a tener una carga virtual grande. Por ello, la finalidad del proyecto era explorar las posibilidades de las metodologías activas de aprendizaje más allá de la docencia presencial, trasladándose al Campus virtual. De esta forma pretendíamos que los/as estudiantes fueran agentes activos en su propio aprendizaje mediante la adaptación de estas metodologías activas a esta nueva realidad educativa

A NOTCH1-driven MYC enhancer promotes T cell development, transformation and acute lymphoblastic leukemia

Efforts to identify and annotate cancer driver genetic lesions have been focused primarily on the analysis of protein-coding genes; however, most genetic abnormalities found in human cancer are located in intergenic regions. Here we identify a new long range-acting MYC enhancer controlled by NOTCH1 that is targeted by recurrent chromosomal duplications in human T cell acute lymphoblastic leukemia (T-ALL). This highly conserved regulatory element, hereby named N-Me for NOTCH MYC enhancer, is located within a broad super-enhancer region +1.47 Mb from the MYC transcription initiating site, interacts with the MYC proximal promoter and induces orientation-independent MYC expression in reporter assays. Moreover, analysis of N-Me knockout mice demonstrates a selective and essential role of this regulatory element during thymocyte development and in NOTCH1-induced T-ALL. Together these results identify N-Me as a long-range oncogenic enhancer implicated directly in the pathogenesis of human leukemia and highlight the importance of the NOTCH1-MYC regulatory axis in T cell transformation and as a therapeutic target in T-ALL. © 2014 Nature America, Inc. All rights reserved. a r t i c l e s advance online publication nature medicine Supplementary Tables 1 and 2). We identified no duplications in this region in 258 non-T-ALL hematologic tumors, and no germline copy number variant polymorphisms encompassing this area have been reported. Moreover, analysis of normal (remission) DNA confirmed the somatic origin of these copy number alterations in all four cases with available material To functionally characterize the potential role of this NOTCH1 binding site in gene regulation, we performed local ChIP analysis of chromatin regulatory factors and epigenetic histone marks in HPB-ALL T-ALL cells. These analyses confirmed high levels of NOTCH1 binding at this site and revealed bona fide active enhancer features associated with this region, including occupancy and high levels of P300 (also called EP300) and histone H3 Lys4 monomethylation (H3K4me1) with low levels of H3K4 trimethylation (H3K4me3) ( On the basis of these results, we proposed that this +1.4 Mb MYC NOTCH1-occupied enhancer-hereby named N-Me for NOTCHbound MYC enhancer-could function as an important regulatory element driving the activation of MYC downstream of NOTCH1 in T-ALL. Consistent with this hypothesis, chromatin configuration 3C (chromosome conformation capture) analysis of the MYC locus demonstrated the association of this enhancer with proximal regulatory sequences in the MYC promoter The N-Me enhancer is required for thymocyte development To test the specificity and functional relevance of the N-Me enhancer in T cell development and transformation, we used homologous recombination in mouse embryonic stem cells to generate N-Me knockout and conditional knockout mice N-Me is required for NOTCH1-induced T cell leukemogenesis Given the important role of NOTCH1-induced MYC upregulation in the pathogenesis of T-ALL, we hypothesized that deletion of the N-Me enhancer could disrupt NOTCH1-induced leukemogenesis. To test this possibility, we transplanted isogenic C57BL/6 mice with wild-type or N-Me heterozygous or homozygous knockout hematopoietic progenitors infected with retroviruses driving the expression of an To explore the pathogenic role of N-Me-mediated Myc expression in NOTCH1-induced leukemia tumor maintenance, we generated ∆E-NOTCH1-induced T-ALL tumors from wild-type (Rosa26TM-Cre N-Me +/+ ) and tamoxifen-inducible conditional heterozygous (Rosa26TM-Cre N-Me flox/+ ) and homozygous (Rosa26TM-Cre N-Me flox/flox ) N-Me knockout hematopoietic progenitors. In these experiments, mice transplanted with ∆E-NOTCH1-expressing wildtype and tamoxifen-inducible heterozygous and homozygous conditional N-Me knockout cells developed NOTCH1-induced T-ALLs with identical kinetics and immunophenotypes ( To better assess the mechanisms mediating the antileukemic effects of N-Me inactivation, we then analyzed the cellular and transcriptional phenotypes of N-Me conditional inducible knockout T-ALL cells after tamoxifen treatment. In this setting, N-Me deletion in T-ALL cells DISCUSSION NOTCH1 has a central role in the pathogenesis of T-ALL 24 and drives an oncogenic transcriptional program that promotes cell growth proliferation and survival in T-ALL lymphoblasts. Importantly, the oncogenic effects of NOTCH1 are closely linked to activation of the MYC oncogene © 2014 Nature America, Inc. All rights reserved. a r t i c l e s nature medicine advance online publication a broad regulatory area of about 100 kb located 1.7 Mb telomeric to the Myc gene, 400 kb downstream of N-Me 35 . This Myc regulatory region contains multiple enhancers that are active in myeloid cells but not the thymus and is duplicated in about 3% of acute myeloid leukemias The requirement for N-Me-mediated upregulation of Myc expression downstream of Notch1 was even more apparent in the context of leukemia initiation, where loss of one and two copies of N-Me delayed and abrogated tumor development by oncogenic NOTCH1, respectively. In addition, N-Me was also required for the maintenance of NOTCH1-induced leukemias, as secondary deletion of one copy of N-Me in established tumors resulted in a marked delay in tumor progression, and loss of two copies effectively abrogated leukemia propagation and the self-renewal capacity of leukemia-initiating cells. These results are consistent with the well-established quantitative effects of MYC expression in other tumor settings. Loss of one copy of Myc has been shown to attenuate intestinal tumorigenesis 37 , and homozygous deletion of Myc completely abrogates tumor development induced by loss of Apc in the gut Several lines of evidence support a role for loss of Myc expression as the primary driver in the developmental and tumor phenotypes associated with N-me loss. In this regard, we observed marked reductions in Myc expression in developing T cells from N-Me knockout mice and in T-ALL lymphoblasts after N-Me inactivation. Moreover, retroviral expression of Myc restored T cell lymphopoiesis from NMe-deficient hematopoietic progenitors and rescued the defects in leukemia cell growth induced by secondary deletion on N-Me in NOTCH1-induced T-ALL cells. In addition, MYC inactivation has been associated with a global decrease in transcriptional activity, with a particularly pronounced downregulation of genes involved in growth, proliferation and metabolism The generation of the N-Me conditional knockout model presented here was also useful in analyzing the specific role of this enhancer in transcriptional control. Thus, even though in some cases enhancerpromoter interactions have been implicated in the regulation of transcription by promoting the release of RNA Pol II pausing 42 , deletion of N-Me in T-ALL lymphoblasts resulted in unloading of RNA Pol II at the Myc transcription initiation site without any apparent increase in RNA Pol II pausing. Overall, our results identify the N-Me regulatory sequence as a critical mediator of NOTCH1-induced MYC expression that is required for T cell development and transformation and substantiates a pathogenic role for chromosomal duplications targeting this enhancer in the pathogenesis of T-ALL. METHODS COMPETING FINANCIAL INTERESTS The authors declare no competing financial interests. Reprints and permissions information is available online at http://www.nature.com/ reprints/index.html. Curr. Top. Microbiol. Immunol. 360, 163-182 (2012 NOTCH1 inhibition. We inhibited NOTCH1 in JURKAT cells with 250 nM DBZ ((S)-2-(2-(3,5-difluorophenyl)acetamido)-N-((S)-5-methyl-6-oxo-6,7-dihydro-5H-dibenzo [b,d]azepin-7-yl) propanamide) (Syncom) for 48 h as described previously Genomic analysis of primary T-ALL samples. A total of 160 cases of T-ALL from adult and pediatric patients referred to Saint-Louis Hospital, Paris, France were analyzed for copy number abnormalities using array-comparative genomic hybridization with informed consent under the supervision of the Institutional Review Board of the Institut Universitaire d'Hématologie, Université ParisDiderot. Sureprint G3 human CGH 180K, 244K, 400K or 1M arrays (Agilent technologies) were used, and copy number alterations were identified using Genomic Workbench software and the ADM-2 algorithm (Agilent Technologies) as described previously T-ALL oncogenic subtype was determined on the basis of gene expression profiling, as reported previousl

Prácticas artísticas para la sensibilización de la comunidad universitaria hacia las persona afectadas de alzheimer y otras demencias

Depto. de Escultura y Formación ArtísticaFac. de Bellas ArtesFALSEsubmitte

Photostability and photocatalytic degradation of ionic liquids in water under solar light

The aim of this work is to study, (i) the photostability of different imidazolium and pyridinium ionic liquids (ILs) in water under solar light; and (ii) the photocatalytic degradation of those ILs in water with TiO 2 under solar light. The effects of the type of cation and anion as well as the length of the cationic chain of the imidazolium ILs have been analyzed. These imidazolium-based ILs show high solar stability, slightly decreasing as the length of the cationic chain increases. The anion plays a main role in the stability of ILs under solar light, decreasing in the case of hydrophobic anions. The kind of head group (pyridinium or imidazolium) or the presence of functional groups (allyl, OH) also influence the solar light stability. DFT calculations on the fundamental and excited electronic states of the ILs were carried out to obtain a deeper insight on their photostability. In the case of the photocatalytic degradation of the ILs, complete conversion was achieved for all the ILS tested but mineralization reached 80% at the most. The rate of degradation increased with the length of the alkyl chain while the anion showed little effect. The pyridinium-based IL tested was the easiest to breakdownThe authors acknowledge the financial support from Spanish MINECO (projects CTQ2013-41963-R and CTQ2016-78576-R) and Comunidad Autónoma de Madrid (project S2013/MAE-2800). We are very grateful to Centro de Computación Científica de la Universidad Autónoma de Madrid for computational facilitie