Alberto Sols Biomedical Research Institute
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Tratamiento de datos personales en la lucha contra la pandemia por la Covid-19. Las medidas de excepción y principio de proporcionalidad
No full textEste trabajo tiene como objeto analizar las garantías del
tratamiento de los datos de carácter personal realizados
desde los desarrollos tecnológicos articulados para la
gestión de la pandemia causada por la COVID-19. El análisis
de dichas garantías se afronta desde dos perspectivas que
terminan convergiendo. Desde la primera perspectiva, el
estudio de las garantías del derecho a la protección de datos
personales se realiza a partir de los documentos emanados
tanto desde las instituciones europeas, especialmente el
Comité Europeo de Protección de Datos, como desde la
Agencia Española de Protección de Datos, que interpretan
la aplicación del Reglamento General de Protección de
Datos en esta situación de pandemia. El estudio se
complementa con una segunda perspectiva en la que se
analizan sistemáticamente las exigencias que conlleva el
respeto a los derechos fundamentales, como es el derecho a
la protección de datos de carácter personal, tomando como
referencia la STC 76/2019, aún en situaciones de
emergencia e incertidumbre científica. Dicho análisis se
realiza desde dos planos: el plano normativo y plano de
aplicación del Derecho vigenteThe purpose of this work is to analyze the guarantees for the
processing of personal data for the management of the
pandemic caused by COVID-19, from the technological
developments articulated for the control of the virus. The
analysis of these guarantees is approached from two
perspectives that end up converging. From the first
perspective, the study of the guarantees of the right to the
protection of personal data is carried out from the
documents issued both from the European institutions,
especially the European Data Protection Committee, and
from the Spanish Agency for Data Protection, which
interpret the application of the General Data Protection
Regulation in this pandemic situation. The study is
complemented with a second perspective in which the
demands that the respect for fundamental rights entails,
such as the right to the protection of personal data, are
systematically analyzed, taking as reference STC 76/2019,
even in emergency and scientific uncertainty situations.
This analysis is carried out from two levels: the normative
level and the application of current La
El reparto de anticipos con cargo a la cuota de liquidación
No full textEl reconocimiento de personalidad jurídica a las sociedades de capital
(art. 33 LSC) exige garantizar la prioridad absoluta de los acreedores
sociales frente a los socios en la liquidación. Esta regla de prioridad (art.
391 LSC) ha sido interpretada de forma particularmente rigurosa por la
doctrina y por la Dirección General de los Registros y del Notariado, que
entienden que, hasta que no se haya satisfecho íntegramente el pasivo y
no haya adquirido firmeza el acuerdo por el que se aprueba el balance
final y el proyecto de división (art. 394 LSC), queda vedada cualquier
distribución a los socios ya sea directa, en forma de dividendos o de
anticipos sobre la cuota, o indirecta, mediante la adquisición de acciones
o participaciones propias o a través de la reducción del capital con
restitución de aportacionesEste
trabajo se realizó en el marco del Proyecto de Investigación «La adaptación al
Derecho europeo de la empresa: los nuevos retos del Derecho de sociedades y de
los mercados de capitales», concedido por el Ministerio de Ciencia e Innovación,
del que son Investigadores Principales los Profesores Aurora Martínez Flórez
y Alberto Vaquerizo Alons
Perceived usability of collaborative modeling tools
No full textContext: Online collaborative creation of models is becoming commonplace. Collaborative modeling using chatbots and natural language may lower the barriers to modeling for users from different domains. Objective: We compare the perceived usability of two similarly online collaborative modeling tools, the SOCIO chatbot and the Creately web-based tool. Method: We conducted a crossover experiment with 66 participants. The evaluation instrument was based on the System Usability Scale (SUS). We performed a quantitative and qualitative exploration, employing inferential statistics and thematic analysis. Results: The results indicate that chatbots enabling natural language communication enhance communication and collaboration efficiency and improve the user experience. Conclusion: Chatbots need to improve guidance and help for novices, but they appear beneficial for enhancing user experienceThis research was funded by the Spanish Ministry of Science, Innovation, and Universities research grants PGC2018-097265-B-I00 and the FINESSE project (PID2021-122270OB-I00). This research was also supported by the Madrid Region R&D program (project FORTE, P2018/TCS-4314) and the SATORI-UAM project (TED2021-129381B-C21
El pensamiento filosófico de Antonio Machado en sus ''Apócrifos''
No full textTesis Doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Filosofía y Letras, Departamento de Antropología Social y Pensamiento Filosófico Español. Fecha de Lectura: 11-07-2023Esta tesis tiene embargado el acceso al texto completo hasta el 11-01-2025El objetivo de esta Tesis es investigar el pensamiento filosófico de Antonio Machado en sus dos apócrifos: Abel Martín y Juan de Mairena. Estos dos personajes ficticios se representan como portavoces de la ideología que planteaba Machado a inicios del siglo XX, para transmitir sus consideraciones con respecto a temas tanto literarios como filosóficos.
Mientras tanto, la historiografía sería indispensable en cuanto a exponer el panorama histórico y el desarrollo de las proposiciones del autor. En virtud de ello, se va a considerar primariamente el periodo que va desde los finales del siglo XIX hasta los principios del siglo XX, con el fin de contextualizar los siguientes capítulos, sirviéndonos como sedimento histórico e intelectual de nuestro estudio. En la segunda parte, se emprende la reconstrucción de una trayectoria general de la carrera de Machado y la búsqueda del origen de su interés por la filosofía; asimismo, se enlaza su pensamiento con los intelectuales que más influyen en el pensar filosófico de nuestro poeta: en este caso, Miguel de Unamuno y Henri Bergson. La tercera parte intenta proporcionar una exposición global que esclarece las proposiciones metafísicas más relevantes en Abel Martín y Juan de Mairena en torno a problemas del amor, la objetividad, la existencia, el ser y el diálogo, etc. La última parte es la conclusión, en la que se van a resumir todos los argumentos referidos a lo largo de esta Tesis y a plantear una breve expectativa sobre la investigación en el futuroThe aim of the thesis is to investigate the philosophical thought of Antonio Machado in his two fictitious characters: Abel Martín y Juan de Mairena. These two fictitious characters are represented as spokespersons of the ideology that Machado created to transmit his considerations on issues about literature and philosophy from the beginning of the 20th century.
Meanwhile, the historiography is indispensable with respect to the historical scenery and the development of his proposals. In accordance with this reason, the research will focus on the period, particularly from the end of 19th century to the beginning of the 20th century, to contextualize the following chapters. Also, this part will be served as a historical and intellectual sediment of our research. The second part attempts to build up a general trajectory about his literary career and to find the origin of Machado´s interest on philosophy. At the same time, I will try to connect his thoughts with those intellectuals who had a huge influence on his philosophical thinking; specifically, Miguel de Unamuno and Henri Bergson. In the third part, I will provide a global and concrete interpretation that clarifies the most significant metaphysical proposals in Abel Martín and Juan de Mairena, in which we will talk about problems related to love, objectivity, existence, being and dialogue, etc. The last part is a conclusion which summarizes all the arguments that we mentioned before in the thesis and makes a brief expectation for the future investigatio
Identificación de nuevas dianas terapéuticas en el carcinoma escamoso de pulmón mediante CRISPR/Cas9
No full textTesis Doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Ciencias, Departamento de Biología Molecular. Fecha de Lectura: 23-02-2023Esta tesis tiene embargado el acceso al texto completo hasta el 31-12-2025NRF2 is the master regulator of the antioxidant response, whose activity is regulated by KEAP1. Several reports have related this transcription factor to the development of cancer. In fact, the overactivation of this signaling pathway has been found in several tumor types including lung adenocarcinoma (LUAD). However, less is known about its role in lung squamous cell carcinoma (LUSC) and the targeted therapies available. In this sense, some studies indicated that this pathway was mainly altered in LUSC tumours (~30-40%), suggesting an important role for its development. All these findings together prompted the study of NRF2/KEAP1 in LUSC in more detail, including the consequences of its interference as well as the study of targetable downstream genes related with this signaling pathway.
In this work it was found that NRF2/KEAP1 pathway was overactivated in LUSC samples harboring NFE2L2/KEAP1 alterations. This fact makes the active NRF2 LUSC behaves as resistant to cell death by oxidative stress (OS) challenge in comparison to WT NRF2 tumors. With the hypothesis in mind of such tumors been addicted to NRF2, the consequences of NFE2L2 silencing were studied in vitro, by using stable Tet-On shRNA NFE2L2 clones of LUSC cell lines. Cell viability was drastically reduced upon induction of OS in the active NRF2 cell line after NFE2L2 silencing. In the case of in vivo experiments, the silencing of NFE2L2 in a xenograft model with the active NRF2 LUSC cell line, reduced tumor growth, suggesting a potential role of NRF2 as a tumor driver in LUSC. Confirmation of NRF2-dependence for LUSC samples with active NRF2 aimed the study of potential downstream genes of this pathway. These were studied by using the CRISPR/Cas9 activation (a) technology. It was used the CRISPRa/dCas9 SAM system, whose efficiency was tested by confirming the increase in gene expression using a sgRNA for CXCR4. The use of the sgRNA library in the active NRF2 LUSC cells subjected to NRF2 depletion and OS, permitted a partial survival recovery. This suggests that some sgRNAs from the library induced the increase expression of survival genes. Further NGS analyses and validation indicated three possible genes as downstream survival gene candidates. After several validations, one of them stands out as a potential novel target gene in LUSC harboring NFE2L2/KEAP1 alterations, opening a new field of study for future targeted therapie
Dinámica de Portadores de Carga Libres, Excitones y Fonones Fotogenerados en Silicio
No full textTesis Doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Ciencias, Departamento de Física Aplicada. Fecha de Lectura: 06-03-2024Esta Tesis tiene embargado el acceso al texto completo hasta el 06-09-202
Papel de los genes mitocondriales en el desarrollo de cardiotoxicidad: identificación de biomarcadores predictivos
No full textTesis Doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Ciencias, Departamento de Biología Molecular. Fecha de Lectura: 15-04-2024Esta tesis tiene embargado el acceso al texto completo hasta el 15-10-2025Anthracyclines are one of the most used and widespread chemotherapeutic compounds used in a large number of cancer types due to its efficacy. Notwithstanding, they also present a worrisome adverse drug reactions, the anthracycline-induced cardiotoxicity that appears in a big number of survivors.
While certain clinical risk factors have been recognized, they are not enough to reliably predict the onset of this severe side-effect, suggesting that genetic factors may also significantly contribute to the inter-individual variability found. For that reason, in the last years, several studies have tried to identify the genetic risk component, however only a very limited number of them have been successfully identified.
With this scenario, this Thesis aimed to identify new genes that may allow to gain some understanding in the molecular basis of this chronic cardiotoxicity in breast cancer patients that might allow for a better risk stratification, so clinicians would be able to know which patients will have a higher risk of developing this side-effect.
Although the precise mechanisms responsible for anthracycline-induced cardiotoxicity remain elusive, there is accumulating evidence suggesting a significant contribution of the mitochondria to this phenomenon.
Considering this, this Thesis explores the role of both, common and rare variations in nuclear mitochondrial genes, along with DNA mitochondrial variations, in patients treated with anthracyclines who either developed cardiotoxicity or not.
We have been able to identify variations in the expression levels of POLRMT, the mitochondrial RNA polymerase, as linked with the risk of developing epirubicin-induced cardiotoxicity, together with rarer deleterious variants in STYLX1, are directly related with a higher susceptibility to develop anthracycline-induced cardiotoxicity.
Finally the mitochondrial genome study in these patients showed that the presence of predicted deleterious variants in the coding regions of the subunits of the complex 1 of the mitochondrial electronic transport chain were directly related to a lower likelihood of developing anthracycline-induced cardiotoxicity.
In conclusion, the results of this Thesis imply a significant advancement in understanding the molecular mechanisms and genetic bases associated with this toxicity. The identification of these genetic markers reveals a multifactorial and polygenic model, indicating that multiple factors and a combination of genetic variations contribute to the response to anthracyclines in breast cancer patients. This Thesis research opens the door to more personalized clinical approaches, promising to enhance treatment effectiveness and reduce associated risks. This progress marks a significant milestone toward healthcare that is more attuned to the individual needs of these patients, representing a crucial step in advancing the field of personalized medicine for breast cance
Desarrollo de anisotropía perpendicular magnética en láminas delgadas de Nd,Pr)FeB
No full textTesis Doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Ciencias, Departamento de Física de la Materia Condensada. Fecha de Lectura: 19-09-2023Esta Tesis tiene embargado el acceso al texto completo hasta el 19-03-202
Impacto de los productos de glicación avanzada en las propiedades mecánicas de la titina
No full textTesis Doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Medicina, Departamento de Bioquímica. Fecha de Lectura: 26-10-2023Esta tesis tiene embargado el acceso al texto completo hasta el 26-04-2025Post-translational modifications (PTMs) are common changes that occur to proteins by, for
example, addition of small molecules. Those modifications have a wide range of effects and are able to
modulate protein stability, localization, function or even their mechanical properties, which has been
linked to the pathophysiology of various conditions, including cancer, neurodegeneration or
cardiovascular diseases. One type of PTM is non-enzymatic glycation, which is a hallmark of aging and
diseases like diabetes. It has been shown that glycation leads to formation of intermolecular crosslinking
advanced glycation end products (AGEs) in extracellular proteins, which contribute to cardiac tissue
stiffening observed in both situations. Nevertheless, the alteration of extracellular proteins cannot
explain why increased rigidity is observed in diabetic or aged cardiomyocytes. Here, we have studied
whether titin, the largest protein encoded by the human genome and a key contributor to cardiomyocyte
mechanics, is the target of glycation that can affect its mechanical properties. We focused on glycation
induced by methylglyoxal (MG), a major glycating agent in diabetes. Specifically, we have used singlemolecule
nanomechanical profiling by Atomic Force Microscopy (AFM) to examine how MG-induced
glycation affects the mechanics of titin domains. Our results demonstrate that MG leads to prominent
formation of intradomain crosslinks in titin, which causes increased protein stiffness due to the
reduction of its contour length and faster folding kinetics. We also show that MG increases
cardiomyocyte passive tension, a parameter that is directly related to titin mechanical properties. By
running Monte Carlo simulations, we were able to provide a mechanistic explanation for the increased
titin-based cardiomyocyte stiffness, pointing to the fundamental contribution of contour length
reduction in titin random coil regions upon glycation. We have also obtained evidence that titin
glycation is increased in aged myocardium, suggesting that our observations can have
pathophysiological relevance. We propose that the presence of intradomain crosslinks in proteins can
contribute to changes in the mechanical properties of diabetic and aged tissuesLas modificaciones postraduccionales son cambios comunes que afectan a proteínas mediante, por
ejemplo, la adición covalente de pequeñas moléculas. Dichas modificaciones tienen un gran rango de
efectos y son capaces de modular la estabilidad y función de proteínas, o incluso sus propiedades
mecánicas, lo cual ha sido relacionado con la fisiopatología de diversas patologías, incluyendo cáncer
y enfermedades neurodegenerativas o cardiovasculares. Un tipo de estas modificaciones es la glicación
espontánea, la cual ocurre por ejemplo durante el envejecimiento y en patologías como la diabetes. Se
ha descrito que la glicación da lugar a la formación de productos de glicación avanzada (AGEs) capaces
de generar entrecruzamientos intermoleculares entre proteínas extracelulares, lo cual contribuye a la
rigidificación del tejido cardiaco en ambas situaciones. Sin embargo, la alteración de las proteínas
extracelulares no es capaz de explicar por qué los propios cardiomiocitos envejecidos o diabéticos son
intrínsicamente más rígidos. En este trabajo, hemos estudiado si la glicación de titina, la proteína de
mayor tamaño codificada por el genoma humano y elemento clave respecto a la mecánica del
sarcómero, altera sus propiedades mecánicas pudiendo contribuir a la rigidificación de cardiomiocitos.
Nos hemos centrado en la glicación inducida por metilglioxal (MG), un importante agente que produce
glicación en diabetes. Realizamos una caracterización mecánica de molécula individual mediante
técnicas de Microscopía de Fuerza Atómica (AFM). Nuestros resultados demuestran que el MG provoca
una notable formación de entrecruzamientos intradominio en titina, causando un aumento de la rigidez
de la proteína debido a la reducción de su longitud de contorno y al aumento de su cinética de
plegamiento. Además, también mostramos que el MG aumenta la tensión pasiva de cardiomiocitos, una
propiedad que depende directamente de las propiedades mecánicas de la titina. Mediante la ejecución
de simulaciones de Monte Carlo, hemos sido capaces de proporcionar una explicación mecanicista al
incremento de la rigidez de cardiomiocitos con relación a la titina, señalando la contribución
fundamental de la reducción de la longitud de contorno de las regiones no estructuradas de titina al ser
glicadas. Asimismo, hemos encontrado evidencia de que la glicación en titina aumenta en el miocardio
envejecido, lo que sugiere que nuestras observaciones tienen relevancia patofisiológica. Nuestros
resultados sugieren que la presencia de entrecruzamientos intradominio en proteínas puede afectar a las
propiedades mecánicas de tejidos diabéticos y envejecidosThis PhD Thesis project has been funded by Ministerio
de Ciencia e Innovación (BIO2017-83640-P and PID2020-120426GB-I00