The chromatin remodeller BPTF is a novel and critical c-MYC co-factor

Tesis doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Ciencias, Departamento de Biología Molecular. Fecha de lectura: 23-07-2015c-MYC is a major oncogene involved in human cancer. Here, I have identified BPTF as a novel interactor of c-MYC required for its biological functions. This interaction is crucial for c-MYC transcriptional activity: BPTF knock-down leads to a decrease in c-MYC binding to DNA, changes in chromatin accessibility, and impaired activation of the c-MYC transcriptional program. In murine embryonic fibroblasts, BPTF is necessary for c-MYC-driven proliferation, G1-S progression, and replication stress, but not for c-MYC-induced apoptosis. Moreover, BPTF is critical for reprogramming of somatic cells into induced pluripotent stem cells using the four Yamanaka factors. In agreement with these findings, BPTF is required for the proliferation of c-MYC-addicted cancer cells and in human tumors its expression positively correlates with the activation of c-MYC gene signatures. To determine whether BPTF is required for the oncogenic effects of c-MYC, we used two genetic mouse models: Ela-Myc and E -Myc. Ela-Myc mice develop aggressive acinar and ductal tumors. While BPTF is dispensable for normal pancreatic development and differentiation, its embryonic inactivation in ElaMyc mice is associated with extensive loss of acinar cells. Moreover, deletion of BPTF in young Ela-Myc via activation of the Ptf1a-CreERT2 recombinase results in a significant delay in tumor onset and a corresponding extension in disease-free survival. c-MYC overexpression in the B cell lineage (E -Myc) leads to the development of Burkitt-like lymphomas. Inactivation of one Bptf allele does not impair B cell maturation but completely blocks lymphoma development. These findings underscore the importance of a more detailed study of BPTF function in mammals and highlight the potential of exploiting the c-MYC:BPTF axis in cancer therapy.c-MYC es uno de los principales oncogenes implicados en el cáncer humano. En el presente trabajo he identificado a BPTF como un nuevo interactor de c-MYC que además es requerido para sus funciones biológicas. Esta interacción es crucial para la actividad transcripcional de c-MYC: el knock-down de BPTF se acompaña de una disminución de la unión de c-MYC al DNA, cambios en la accesibilidad de la cromatina y de una inadecuada activación del programa transcripcional de cMYC. En fibroblastos embrionarios de ratón, BPTF es necesario para la proliferación, progresión G1-S y estrés replicativo dirigidos por c-MYC, pero no para la apoptosis instruida por el mismo. Además, BPTF es crítico para la reprogramación de células somáticas a células madre pluripotentes por medio de los cuatro factores descritos por Yamanaka. De acuerdo con estas observaciones, BPTF es necesario para la proliferación de líneas cancerosas adictas a c-MYC, y en tumores humanos su expresión correlaciona positivamente con la activación de los programas de expresión génica dirigidos por c-MYC. Con el objetivo de determinar si BPTF es necesario para los efectos oncogénicos de c-MYC, hemos usado dos modelos genéticos de ratón: Ela-Myc y E -Myc. Los ratones Ela-Myc desarrollan tumores acinares y ductales muy agresivos. Aunque BPTF es dispensable para la diferenciación y desarrollo pancreáticos normales, su inactivación embrionaria en ratones Ela-Myc se asocia con una extensa pérdida de células acinares. Además, la depleción de BPTF en ratones Ela-Myc jóvenes por medio de la recombinasa Ptf1a-CreERT2 resulta en un retraso significativo en la aparición de los tumores y en una consiguiente extensión de la supervivencia libre de enfermedad. La sobre-expresión de c-MYC en el compartimento de células B conduce al desarrollo de linfomas que reproducen la enfermedad del Linfoma de Burkitt. La inactivación de una sola copia de Bptf no afecta a la maduración de las células B pero bloquea por completo la formación de tumores. Estas observaciones destacan la importancia de un estudio más detallado de la función de BPTF en mamíferos y subrayan el potencial de explotar el eje c-MYC:BPTF como blanco terapéutico en cáncer.The work was supported by grants from Ministerio de Economía y Competitividad, Madrid, Spain (grants Consolíder ONCOBIO, Consolider INESGEN, SAF2010-21517 and SAF2011-15934-E), Instituto de Salud Carlos III (grants G03/174, 00/0745, PI051436, PI061614, G03/174, PI080440, PI120425 and Red Temática de Investigación Cooperativa en Cáncer (RTICC)), Asociación Española Contra el Cáncer, EUFP7-201663 and 201333, and US National Institutes of Health grant RO1 CA089715

Low temperature oxide desorption in GaAs (111)A substrates

The aim of this work is to study oxide removal processes on GaAs (111) A substrates previous to epitaxial growth. We have studied conventional thermal desorption and processes based on the reduction of surface oxides by deposition of gallium, indium and exposure to atomic hydrogen. We have determined substrate temperatures (Ts) for optimum oxide removal in epi-ready substrates by the different studied processes: Ts = 540 °C for thermal desorption, Ts = 505 °C for indium deposition and Ts = 400 °C for oxide desorption by exposure to atomic hydrogen. All these processes allow for a subsequent good quality epitaxial growth. These results cannot be directly extended to oxide removal in grown samples that have been exposed to air outside the growth chamber. In this case, we have found that only indium deposition and exposure to atomic hydrogen are compatible with regrowth processes.We acknowledge financial support from Spanish MINECO (Grant TEC2011-29120-C05-04), and CAM (Grant S2009ESP-1503). Jesús Herranz acknowledges the JAE program for the funds.Peer Reviewe

Deep learning of quantum entanglement from incomplete measurements

The quantification of the entanglement present in a physical system is of paramount importance for fundamental research and many cutting-edge applications. Currently, achieving this goal requires either a priori knowledge on the system or very demanding experimental procedures such as full state tomography or collective measurements. Here, we demonstrate that by employing neural networks we can quantify the degree of entanglement without needing to know the full description of the quantum state. Our method allows for direct quantification of the quantum correlations using an incomplete set of local measurements. Despite using undersampled measurements, we achieve an estimation error of up to an order of magnitude lower than the state-of-the-art quantum tomography. Furthermore, we achieve this result employing networks trained using exclusively simulated data. Finally, we derive a method based on a convolutional network input that can accept data from various measurement scenarios and perform, to some extent, independently of the measurement device.Comment: 10 pages, 5 figures, 1 tabl

New organic platform to integrated photonic device fabrication

This paper presents a new technological platform for the development of integrated optical circuits for applications in photonics. It is based on supramolecular polymeric materials whose behaviour resembles that of those known as vitrimers. These were synthesized by reaction between diglycidyl ether of bisphenol A (DGEBA) and different n-alkylamines. The photonic characteristics of thin films made from these polymeric systems using the spin coating technique on commercial glass substrates are presented. The reflectivity curves of coupled laser light in the films through a high refractive index prism are also shown and analysed. From these results, thin films show guided modes in both polarizations (TE-TM) for electromagnetic radiation in the UV-visible range. Likewise, from the experimental data, the refractive index and thickness of the explored films are determinedEste trabajo ha sido parcialmente financiado por los proyectos PICT-2016-4086, PICT-2017-0017 y PICT-2018-2309 de la Agencia Nacional de Promoción Científica y Tecnológica. Además, este trabajo fue financiado también por los proyectos PUNQ and PPROF de la Universidad Nacional de Quilmes, Ambas instituciones públicas de la República Argentina. Fue también financiado por el proyecto PID2019-110632RB-I00 del Ministerio de Ciencia e Innovación (España), por la European Union's Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement No 814299 (proyecto VIT) y por FCT/MCTES, (Fundação para a Ciência e Tecnologia and Ministério da Ciência, Tecnologia e Ensino Superior, Portugal) poyectos UIDB/50006/2020 y UIDP/50006/202

Low temperature oxide desorption in GaAs (111)A substrates

Trabajo presentado al 17th european Molecular Beam Epitaxy Workshop celebrado en Levi (Finlandia) del 10 al 13 de Marzo de 2013.Peer Reviewe

Production of metal-free diamond nanoparticles

In this paper, the controlled production of high-quality metal-free diamond nanoparticles is demonstrated. Milling with tempered steel is shown to leave behind iron oxide contamination which is difficult to remove. Milling with SiN alleviates this issue but generates more nondiamond carbon. Thus, the choice of milling materials is critically determined by the acceptable contaminants in the ultimate application. The removal of metal impurities, present in all commercially available nanoparticles, will open new possibilities toward the production of customized diamond nanoparticles, covering the most demanding quantum applications

Post-growth rapid thermal annealing of InAs quantum dots grown on GaAs nanoholes formed by droplet epitaxy

Trabajo presentado al 16th European Molecular Beam Epitaxy Workshop celebrado en Alpe d'Huez (Francia) del 20 al 23 de Marzo de 2011.The deposition of InAs on GaAs nanoholes formed by droplet epitaxy can be used to tailor the shape and size of InAs QDs while preserving the low areal density (~2x108 cm-2) imposed by the nanohole pattern. Our previous micro photoluminescence (μPL) study of individual InAs QDs grown by this method revealed that the single QD emission was largely affected by the charged environment surrounding the nanostructure. This charged environment, attributed to the presence of As vacancies, leads to multicharged exciton emission and spectral diffusion effects which might limit the suitability of these QDs in quantum light emitting applications. An intense single peaked emission with radiation limited linewidth and null fine structure splitting (FSS) would be desirable to fully exploit the size and shape control capabilities of droplet epitaxy based methods. The aim of the present study is to reduce the presence of the As vacancies near the QDs by applying a post-growth rapid thermal annealing (RTA) to the sample. Besides, the small FSS (~41 μeV) [1] found typically in theseQDs might be reduced further by the RTA processes. Figure 1 shows the ensemble PL of our sample before and after the RTA process at 775º C during 5 minutes. The optimization of the growth procedure explained in [1] gives rise to a narrow emission band centered at 1.296 eV with FWHM=14.6 meV. A blue shift of the PL band and a reduction of the decay time are clearly observed after the RTA without noticeable change of the FWHMT. o study the same single QDs before and after the RTA process we have defined arrays of 2-μm-wide mesa structures on the sample surface (inset Fig. 2). Before the RTA, the s-shell emission is dominated by multicharged exciton complexes and shows narrow emission linewidths (<100 μeV) limited by our spectrometer resolution (Fig. 2). Results after RTA process will be shown.Peer Reviewe

The role of interaction in the development of the students' writing skills. A study using model texts as feedback

Using model texts as a corrective feedback technique is believed to provide students with meaningful feedback, which could lead to the improvement of their writing skills. The aim of this study is to determine whether interaction among peers and with the teacher generated by the use of model texts as feedback has a positive effect on the development of the students' writing skills. To do so, the focus has been put on the differences between the students' initial and final texts. A qualitative and interpretative analysis has been conducted to see whether these differences could be attributed to the discussion during the interactional phase. The results confirm the expectations, although further research is advisable to gain a better understanding of this type of feedbackL'ús de textos model com a tècnica de feedback correctiu pot proporcionar als estudiants un feedback rellevant, que podria conduir a la millora de la seva expressió escrita. L'objectiu d'aquest estudi és determinar si la interacció amb els companys i amb el professor durant l'ús de textos models com a feedback té un efecte positiu en el desenvolupament de l'expressió escrita dels alumnes. Per tal de dur-lo a terme, s'ha posat el focus en les diferències entre els primers textos dels estudiants i les seves històries finals. S'ha realitzat un anàlisi qualitatiu i interpretatiu per veure si aquestes diferències es podrien atribuir a la discussió durant la fase de la interacció. Els resultats confirmen les expectatives, tot i que és aconsellable seguir fent recerca sobre aquest tema, per tal d'aconseguir una millor comprensió sobre aquest tipus de feedback

High extraction efficiency source of photon pairs based on a quantum dot embedded in a broadband micropillar cavity

The generation of photon pairs in single quantum dots is based on a process that is, in its nature, deterministic. However, an efficient extraction of these photon pairs from a high-index semiconductor host material requires engineering of the photonic environment. We report on a micropillar-based device featuring an extraction efficiency of 69.4(10)$\%$ that is achieved by harnessing a broadband operation suitable for extraction of photon pairs emitted from a single quantum dot. Opposing the approaches that rely solely on Purcell enhancement to realize the enhancement of the extraction efficiency, our solution exploits a suppression of the emission into the modes other than the cavity mode. Our technological implementation requires modest fabrication effort enabling higher device yields that can be scaled up to meet the growing needs of quantum technologies. Furthermore, the design of the device can be further optimized to allow for an extraction efficiency of 85$\%$