Hepatic acinus morpho-functional uniqueness in normal and pathological conditions

El hígado es un órgano clave para la homeostasis del organismo con una actividad metabólica distribuida de forma zonal en el acino hepático. Su organización estructural se define por el gradiente de oxígeno recibido y una acción metabólica basada en su expresión enzimática. Su relación de proximidad con los ejes venosos establece las mayores diferencias. La zonación circundante a las áreas portales presenta mayor actividad en la gluconeogénesis, betaoxidación y síntesis proteica mientras que la adyacente a la vena centrolobulillar está más especializada en la glucólisis, lipogénesis y metabolismo xenobiótico. La morfología y distribución de orgánulos del hepatocito expresa una adaptación funcional acorde con su disposición en el acino. Las mitocondrias, retículo endoplasmático rugoso y aparato de Golgi son más abundantes en la región periportal, mientras que el retículo liso, lisosomas y peroxisomas prevalecen en la perivenosa. La diferente susceptibilidad al daño celular según la zonación afectada ayuda a comprender la patogenia de algunas enfermedades hepáticas. La zona periportal es más susceptible a procesos como la inflamación, mientras que la zona perivenosa suele presentar una afectación inicial predominante en toxicidad inducida por fármacos, acúmulo de metabolitos endógenos, o el aumento de lipogénesis experimentada en la esteatosis hepática.The liver is a key organ for maintaining the body´s homeostasis, with its metabolic activity distributed in zonal pattern within the hepatic acinus. Its structural organization is defined by the oxygen gradient it receives, and the metabolic activity based on enzymatic expression. Proximity to the venous axes determines the major differences. The zone surrounding the portal areas shows higher activity in gluconeogenesis, beta-oxidation and protein synthesis, whereas the area adjacent to the central vein is more specialized in glycolysis, lipogenesis and xenobiotic metabolism. The morphology and distribution of hepatocyte organelles reflect a functional adaptation according to their position within the acinus. Mitochondria, rough endoplasmic reticulum and Golgi apparatus are more abundant in the periportal region, while smooth endoplasmic reticulum, lysosomes and peroxisomes prevail in the perivenous region. The varying susceptibility to cellular injury depending on the affected zone provides insights into the pathogenesis of certain liver diseases. The periportal zone is more vulnerable to conditions such as inflammation, whereas the perivenous zone is typically more affected by early stages of drug-induced toxicity, accumulation of endogenous metabolites or increased lipogenesis as seen in hepatic steatosis.Grado en Medicin

Correlation of coronary calcium measured on conventional computed tomography with coronary angiography findings in lung transplant patients

Introduction and objective: The pre-transplant protocol for lung transplant candidates includes a chest CT scan to assess disease progression and often coronary angiography (CA) to rule out coronary artery disease (CAD). Coronary artery calcium is commonly observed in these pre-transplant CT scans. This study aims to evaluate the relationship between coronary calcium detected on CT and findings from CA to determine whether calcium presence could serve as an additional criterion for selecting patients for CA. Material and Methods: We included 252 consecutive lung transplant patients who had both a CT scan and CA within 365 days of each other. Coronary calcium quantification was performed using artery-based, segment artery-based, and visual assessment methods. CA findings were classified by stenosis severity: 20%, 21?70%, and >70%. Results: This study showed very high concordance (kappa = 0.896; 95% CI: 0.843-0.948) between the three methods, especially in distinguishing patients without and with coronary calcium (kappa = 1.000; 95% CI: 0.929-1.071). ROC analysis identified the absence of coronary calcium as the best cutoff to differentiate patients with ?20% stenosis from those with >21%, with a sensitivity of 73.5%, specificity of 55.7%, PPV of 28.5%, and NPV of 90%. Only 11 patients (8.7%) without coronary calcium had stenosis of 21-70%, and only 2 (1.6%) had stenosis > 70%. Conclusions: The visual assessment method yielded results similar to the other two quantification methods

About the fixed point property in topological spaces

En este trabajo, se estudia la propiedad del punto fijo en espacios topológicos. Un espacio topológico X tiene la propiedad del punto fijo si toda aplicación continua f : X → X deja al menos un punto invariante. Esta es una propiedad topológica, ya que se conserva por homeomorfismos. A lo largo de la memoria se presentan, por un lado, ejemplos de espacios que sí cumplen esta propiedad y, por otro, ejemplos que no la satisfacen. También construimos espacios que verifican la propiedad del punto fijo a partir de otros que ya la tienen. En el caso de espacios métricos, probamos el Teorema del punto fijo de Banach y una generalización del mismo. En el último capítulo se introducen diferentes propiedades topológicas como la conexión local, la separabilidad, la compacidad local y se estudia la relación de estas propiedades con la propiedad del punto fijo. En particular, se prueba que un espacio topológico con la propiedad del punto fijo es conexo. También se demuestra que, si un espacio métrico localmente conexo y localmente compacto verifica la propiedad del punto fijo, entonces el espacio es compacto.The present work is a study of the fixed point property in topological spaces. A topological space X is said to have the fixed point property if every continuous map f : X → X leaves at least an invariant point. This is a topological property, as it is preserved under homeomorphisms. Throughout the work, examples of spaces that do satisfy the fixed point property and examples of topological spaces that do not satisfy it are presented. We will also construct new spaces that verify the fixed point theorem from other spaces that already have it. In the case of metric spaces, we will prove the Banach fixed-point theorem and a generalization of it. In the last chapter, different topological properties are introduced such as local connectedness, separability, local compactness and the relation between these topological properties and the fixed point property is studied. In particular, it is proved that a topological space with the fixed point property is connected. Also, it is proved that if a locally connected, locally compact metric spaces has the fixed point property, then it is compact.Grado en Matemática

Internationalization plan: Butrich S.A.C

En un entorno empresarial marcado por la globalización, la internacionalización se presenta como una estrategia esencial para que las marcas con identidad propia amplíen su alcance y generen ventajas competitivas sostenibles. Este Trabajo de Fin de Máster desarrolla un plan de expansión internacional para Butrich, marca peruana de calzado y accesorios de lujo hechos a mano, con el propósito de identificar el mercado más idóneo entre México, Colombia y España para establecer una filial propia mediante inversión directa. El análisis parte de una evaluación interna de la empresa para valorar sus capacidades estratégicas, operativas y organizacionales, lo que permite establecer su grado de preparación para abordar nuevos mercados. A partir de ello, se aplica un enfoque comparativo que integra herramientas como la matriz de selección de mercados y el modelo CAGE, con el fin de examinar variables críticas como las distancias culturales, administrativas, económicas y geográficas entre Perú y los países objetivo. Este enfoque se complementa con el análisis de entorno competitivo, perfil del consumidor y barreras de entrada, ofreciendo una visión integral para la toma de decisiones. Los hallazgos evidencian que Butrich posee una propuesta de valor sólida y diferenciada, con recursos adecuados para abordar el proceso de internacionalización. Tras comparar los tres mercados, Colombia se posiciona como la opción más favorable para una primera incursión, debido a su afinidad cultural, cercanía geográfica y entorno institucional receptivo. Como fase inicial, se plantea una estrategia gradual que combine canales digitales con acciones presenciales como pop-up stores, permitiendo validar la demanda y adaptar la oferta antes de ejecutar la apertura de una filial permanente. Este plan no solo propone una ruta concreta para la expansión internacional, sino que refuerza el posicionamiento global de Butrich como marca latinoamericana de lujo, con fuerte arraigo artesanal, sensibilidad estética y compromiso con la sostenibilidad.In a globalized business environment, internationalization has become a crucial strategy for brands with a strong identity to expand their reach and achieve sustainable competitive advantages. This Master’s Thesis develops an international expansion plan for Butrich, a Peruvian luxury brand specializing in handcrafted footwear and accessories, with the objective of identifying the most suitable market among Mexico, Colombia, and Spain to establish a wholly owned subsidiary through direct investment. The analysis begins with an internal evaluation of the company’s strategic, operational, and organizational capabilities to assess its readiness to enter new markets. Subsequently, a comparative approach is applied using tools such as the market selection matrix and the CAGE framework to examine key factors including cultural, administrative, economic, and geographic distances between Peru and the target countries. This approach is complemented by an analysis of the competitive environment, consumer profiles, and entry barriers, providing a comprehensive basis for decision-making. Findings indicate that Butrich has a strong and differentiated value proposition, with adequate resources to undertake internationalization. After comparing the three markets, Colombia emerges as the most favorable initial destination due to its cultural affinity, geographic proximity, and receptive institutional environment. The recommended entry strategy involves a phased approach that combines digital channels with physical activations such as pop-up stores, allowing demand validation and product adaptation prior to establishing a permanent subsidiary. This plan not only outlines a clear pathway for international expansion but also strengthens Butrich’s global positioning as a Latin American luxury brand rooted in craftsmanship, aes sensitivity, and sustainability commitment.Máster en Dirección de Empresas (MBA

Development of a methodology for determining maximum expected fire scenarios (MEFS) using computational tools in nuclear power plant environments

Máster en Ingeniería Industria

Towards hollow nanoparticles for drug delivery

En este trabajo se ha desarrollado un estudio experimental centrado en la síntesis, caracterización y evaluación de la liberación de fármacos desde nanopartículas huecas de sílice. Estas nanopartículas, ampliamente utilizadas en nanomedicina por sus propiedades fisicoquímicas, fueron diseñadas como posibles vehículos para la liberación controlada de principios activos. Como molécula modelo se utilizó la fluoresceína, dada su sensibilidad óptica y comportamiento anfótero dependiente del pH. Para llevar a cabo la síntesis de las nanopartículas huecas, se sintetizaron nanopartículas de sílice mediante el método sol-gel, seguido de su transformación en estructuras huecas mediante un proceso controlado de degradación del núcleo interno con borohidruro de sodio, en presencia de un agente estabilizante polimérico (PVP). Para la caracterización morfológica de ambas nanopartículas se utiliza microscopía electrónica de transmisión (TEM), mientras que las propiedades texturales de las nanopartículas de sílice huecas se evaluaron con isotermas de adsorción-desorción de nitrógeno. Los resultados confirmaron la formación de nanopartículas huecas con un volumen de poro dominante de aproximadamente 39 nm y una superficie específica de 49,32 m²/g. Finalmente, se estudió la cinética de liberación de una molécula modelo encapsulada mediante espectroscopía UV-Vis en medio fisiológico a pH neutro. En dichas condiciones, se observó una liberación muy rápida del fármaco, alcanzando el estado estacionario en menos de 30 minutos, lo que sugiere un mecanismo de liberación por difusión. Estos resultados evidencian el potencial de las nanopartículas huecas de sílice como sistemas eficientes para la entrega controlada de agentes terapéuticos, si bien se propone optimizar su funcionalización exterior, tanto para prolongar la liberación, como para aumentar su selectividad frente a diferentes tipos de tejidos en aplicaciones futuras.This work presents an experimental study focused on the synthesis, characterization, and drug release evaluation of hollow silica nanoparticles (HSNs). These nanoparticles, widely used in nanomedicine due to their special properties, were designed as potential carriers for controlled drug delivery. Fluorescein was employed as a model compound because of its optical sensitivity and amphoteric nature, which depends on pH. To carry out the synthesis of hollow nanoparticles, silica nanoparticles were first synthesized using the sol-gel method, followed by their transformation into hollow structures through a controlled core degradation process using sodium borohydride, in the presence of a polymeric stabilizing agent (PVP). Transmission electron microscopy (TEM) was used for the morphological characterization of both types of nanoparticles, while the textural properties of the hollow silica nanoparticles were evaluated using nitrogen adsorption-desorption isotherms. The results confirmed the formation of hollow nanoparticles with a dominant pore volume of approximately 39 nm and a specific surface area of 49.32 m²/g. Finally, the release kinetics of an encapsulated model molecule were studied using UV-Vis spectroscopy in a physiological medium at neutral pH. Under these conditions, a very rapid drug release was observed, reaching a steady state in less than 30 minutes, suggesting a diffusion-based release mechanism. These results demonstrate the potential of hollow silica nanoparticles as efficient systems for the controlled delivery of therapeutic agents, although further optimization of their surface functionalization is proposed to both prolong the release and increase their selectivity toward different tissue types in future applications.Grado en Físic

The vestal virgins: from privilege to punishment

Las vestales constituyeron el único colegio sacerdotal de Roma conformado por mujeres. A pesar de gozar de una gran variedad de privilegios, tanto jurídicos como sociales, debían cumplir con obligaciones asignadas, siendo las más importantes custodiar el fuego sagrado del aedes Vestae y guardar castidad mientras ejerciesen el sacerdocio. El incumplimiento de ambas obligaciones era motivo de severos castigos. Este trabajo tiene como objetivo realizar un análisis del estatus de las sacerdotisas de Vesta, de sus funciones y de los castigos impuestos por el incumplimiento del voto de castidad. En el análisis se prestará especial atención a las vestales acusadas, juzgadas y condenadas de incestum, así como a aquellas que quedaron absueltas de la condena. Así pues, este trabajo busca, a través de todos los casos conocidos analizar este fenómeno, que ha dejado una significativa impronta en las fuentes literarias.The vestals were the only priestly college in Rome made up of women. Despite enjoying a wide range of privileges, both legal and social, they had to fulfil certain duties, the most important of which were to guard the sacred fire of the aedes Vestae and to remain chaste while exercising their priesthood. Failure to comply with either of these obligations was grounds for severe punishment. The aim of this paper is to analyse the status of the priestesses of Vesta, their duties and the punishments imposed for breaking their vow of chastity. The analysis will pay special attention to the vestals accused, tried and convicted of incestum, as well as those who were acquitted. Thus, this work seeks, through all known cases, to analyse this phenomenon, which has left a significant mark on literary sourcesGrado en Histori

Machine learning algorithms in controlled donation after circulatory death under normothermic regional perfusion: a graft survival prediction model

Background: Several scores have been developed to stratify the risk of graft loss in controlled donation after circulatory death (cDCD). However, their performance is unsatisfactory in the Spanish population, where most cDCD livers are recovered using normothermic regional perfusion (NRP). Consequently, we explored the role of different machine learning-based classifiers as predictive models for graft survival. A risk stratification score integrated with the model of end-stage liver disease score in a donor-recipient (D-R) matching system was developed. Methods: This retrospective multicenter cohort study used 539 D-R pairs of cDCD livers recovered with NRP, including 20 donor, recipient, and NRP variables. The following machine learning-based classifiers were evaluated: logistic regression, ridge classifier, support vector classifier, multilayer perceptron, and random forest. The endpoints were the 3- and 12-mo graft survival rates. A 3- and 12-mo risk score was developed using the best model obtained. Results: Logistic regression yielded the best performance at 3 mo (area under the receiver operating characteristic curve = 0.82) and 12 mo (area under the receiver operating characteristic curve = 0.83). A D-R matching system was proposed on the basis of the current model of end-stage liver disease score and cDCD-NRP risk score. Conclusions: The satisfactory performance of the proposed score within the study population suggests a significant potential to support liver allocation in cDCD-NRP grafts. External validation is challenging, but this methodology may be explored in other regions

Taxation of inheritances. Reflections on its configuration and its constitutional impact

Este Trabajo de Fin de Grado tiene como objetivo principal analizar la fiscalidad de las herencias en España, centrándose en la configuración problemática del principal impuesto y su impacto con respecto a los principios constitucionales. Las principales preocupaciones que existen actualmente, y sobre las que reflexiono en el trabajo, giran en torno a cuestiones de equidad y justicia fiscal, especialmente en lo que respecta a la distribución desigual de la carga tributaria. Estas preocupaciones sugieren la necesidad de revisar y reformar el sistema fiscal actual, para garantizar una mayor coherencia con los principios constitucionalesThe main objective of this thesis is to analyse inheritance taxation in Spain, focusing on the problematic configuration of the main tax and its impact with respect to constitutional principles. The main concerns that currently exist, and on which I reflect in the paper, revolve around issues of tax equity and fairness, especially with regard to the unequal distribution of the tax burden. These concerns suggest the need to review and reform the current tax system to ensure greater consistency with constitutional principlesGrado en Derech

Serum 3-nitrotyrosine in the cardiovascular disease of patients with systemic lupus erythematosus

3-Nitrotyrosine (3-NT) is a product of tyrosine nitration mediated by reactive nitrogen species such as peroxynitrite anion and nitrogen dioxide. It serves as an indicator of inflammation, cell damage, and nitric oxide production. Systemic lupus erythematosus (SLE) is an autoimmune disorder characterized by multisystem involvement and increased oxidative stress. Notably, cardiovascular (CV) disease has emerged as the leading cause of mortality among SLE patients. Our objective was to investigate the association between serum 3-NT levels and a wide range of disease characteristics in patients with SLE, with a particular emphasis on CV comorbidity. A total of 214 patients with SLE were enrolled. The serum levels of 3-NT as well as the activity (SLEDAI) and damage index (SLICC-SDI) scores, full lipid profile, insulin resistance indices, and carotid subclinical atherosclerosis were assessed. Multivariable linear regression analysis was carried out to study the relationship between 3-NT and clinical and laboratory disease characteristics, especially focusing on CV comorbidities. Except for body mass index, which showed a significant positive correlation, the demographic data and traditional CV risk factors did not correlate with 3-NT. After multivariable adjustments, several disease characteristics, including the disease duration, activity and damage indices, and autoantibody profile, showed significant positive associations with 3-NT. Regarding CV characteristics, several lipid profile molecules showed significant relationships with 3-NT. This was not the case for insulin resistance and subclinical atherosclerosis. Remarkably, patients with a high CV risk by SCORE2 showed higher 3-NT values compared to those with a low risk, although after the multivariable adjustment, this relationship was attenuated (but still showed a trend). In conclusion, serum 3-NT levels demonstrated significant positive correlations with multiple disease characteristics, including the disease activity and damage and the autoantibody profile. The lipid pattern in the SLE subjects also significantly and independently correlated with the 3-NT values. Our findings highlight the pathophysiological role of 3-NT specifically, and peroxidation in general, in patients with SLE.This study has been funded by a grant to IF-A by Fundación Canaria Instituto de Investigación Sanitaria de Canarias (FIISC) through the project PIFIISC23/07. Professor Gonzalez-Gay is funded by the Spanish Research Network RICORS—RD24/0007/0031, through Next Generation EU funds, which support the initiatives of the Recovery and Resilience Mechanism (MRR)