1. Investigación

The resilient modulus (MR) of different pavement materials is one of the most important input parameters for the mechanistic-empirical pavement design approach. The dynamic triaxial test is the most often used method for evaluating the MR, although it is expensive, time-consuming, and requires specialized lab facilities. The purpose of this study is to establish a new model based on Long Short-Term Memory (LSTM) networks for predicting the MR of stabilized base materials with various additives during wet-dry cycles (WDC). A laboratory dataset of 704 records has been used using input parameters, including WDC, ratio of calcium oxide to silica, alumina, and ferric oxide compound, Maximum dry density to the optimal moisture content ratio (DMR), deviator stress (σd), and confining stress (σ3). The results demonstrate that the LSTM technique is very accurate, with coefficients of determination of 0.995 and 0.980 for the training and testing datasets, respectively. The LSTM model outperforms other developed models, such as support vector regression and least squares approaches, in the literature. A sensitivity analysis study has determined that the DMR parameter is the most significant factor, while the σd parameter is the least significant factor in predicting the MR of the stabilized base material under WDC. Furthermore, the SHapley Additive exPlanations approach is employed to elucidate the optimal model and examine the impact of its features on the final result.

Background/Objectives: Corema album berries are edible fruits from the Iberian Atlantic coast, characterized by a rich polyphenolic composition, which endows their juice with potential protective effects against neurodegeneration. This study aimed to evaluate the potential of the relatively lesser-known C. album berries as a novel neuroprotective agent against neurodegenerative diseases. Methods: The phenolic compounds of the juice were characterized using UHPLC-HRMS (Orbitrap). The SH-SY5Y neuroblastoma line was used to determine the preventive effect of the juice against H2O2-induced oxidative stress. Furthermore, neuronal cells were differentiated into dopaminergic and cholinergic lines and exposed to 6-hydroxydopamine and okadaic acid, respectively, to simulate in vitro models of Parkinson’s disease and Alzheimer’s disease. The ability of the juice to enhance neuronal viability under toxic conditions was examined. Additionally, its inhibitory effects on neuroprotective-related enzymes, including MAO-A and MAO-B, were assessed in vitro. Results: Phytochemical characterization reveals that 5-O-caffeoylquinic acid constitutes 80% of the total phenolic compounds. Higher concentrations of the juice effectively protected both differentiated and undifferentiated SH-SY5Y cells from H2O2-induced oxidative damage, reducing oxidative stress by approximately 20% and suggesting a dose-dependent mechanism. Moreover, the presence of the juice significantly enhanced the viability of dopaminergic and cholinergic cells exposed to neurotoxic agents. In vitro, the juice inhibited the activity of MAO-A (IC50 = 87.21 μg/mL) and MAO-B (IC50 = 56.50 μg/mL). Conclusions: While these findings highlight C. album berries as a promising neuroprotective agent, further research is required to elucidate its neuroprotective mechanisms in cell and animal models and, ultimately, in human trials.

Los iberoamericanos conforman uno de los principales grupos sociales de la humanidad, con grandes afinidades y estrechos lazos históricos, de sangre, lengua, cultura e intereses comunes con España y Portugal, y con un gran peso también en Estados Unidos y en España. Además, Iberoamérica es de especial interés para la Fundación Universitaria San Pablo CEU y sus obras por sus actividades en territorio americano, el gran número de alumnos iberoamericanos en sus centros educativos en España, y por su creciente relación con organizaciones educativas y de pensamiento americanas.

This study investigates the role of country-level and individual-level factors on climate change risk perception in 28 European countries. Based on the nature of the data and the research question, a multilevel ordered logit model is used. As individual observations are nested among countries, the data is hierarchical, justifying the use of a multilevel model. The analysis focuses on a dependent variable with ordered categories. Due to its inherent ordinal structure, the response levels convey a meaningful order. The ordered logit model explicitly considers this ordinal nature when modeling the dependent variable. On the country level, this study found that climate change risk perception rises with a higher level of income per capita and a lower level of regulatory quality. The positive effect of the national income level persists after controlling for whether the country had a communist regime past or not. On the individual level, this study found that a higher level of climate change risk perception is exhibited by more educated individuals, those with egalitarian and post-materialistic values, those with a higher interest in politics, and a lower level of personal economic worries. Overall, females express higher levels of climate change risk perception than males, but having younger children at home reduces females’ risk perceptions. Similarly, climate change risk perception levels decrease with age only for women. A series of robustness checks validate the main findings. The research suggests that EU policymakers can enhance climate policies and public engagement by considering differences in income, regulatory quality, historical context, and gender-specific aspects. Insights from this study can guide targeted risk communication.

Tau has a wide variety of essential functions in the brain, but this protein also plays a determining role in the development of Alzheimer's disease (AD) and other neurodegenerative diseases called tauopathies. This is due to its abnormal aggregation and the subsequent formation of neurofibrillary tangles. Tau hyperphosphorylation appears to be a critical step in its transformation into an aggregated protein. However, the exact process, including the cellular events that trigger it, remains unclear. In this study, we employed immunocytochemistry assays on hippocampal sections from AD cases and from tauopathy cases (Braak stage III) with no evidence of cognitive decline, and the P301S mouse model to investigate the colocalization patterns of Tau phosphorylated (p) at specific residues (S202-T205, S214, and T231) within the proline-rich region. Our results show pyramidal neurons in the hippocampus of P301S mice in which Tau is intensely phosphorylated at residues S202 and T205 (recognized by the AT8 antibody), but with no detectable phosphorylation at S214 or T231. These non-colocalizing neurons displayed intensely labeled aggregated pTau deposits distributed through the soma and dendritic processes. However, most of the hippocampal pyramidal neurons are labeled with pTauS214 or pTauT231 antibodies and typically showed a homogeneous and diffuse pTau distribution (not aggregated). This different labeling likely reflects a Tau conformational step, potentially related to the transition from a diffuse tau phosphorylation phenotype (Type 2) into an NFT-like or Type 1 phenotype. We further observed that dendrites of CA3 pyramidal cells are intensely labeled with pTau214 in the stratum lucidum, but not with AT8 or pTauT231. By contrast, analysis of tissue from AD patients or other human tauopathy cases (Braak stage III) with no evidence of cognitive decline revealed extensive colocalization with both antibody combinations in CA1. The complete or mature tangle development may follow a different mechanism in the P301S mouse model or may require more time to achieve the maturity state found in AD cases. Further studies would be necessary to address this question.

El estudio del nacimiento de las universidades en la Europa medieval es revelador y arroja luces sobre la esencia misma de la institución universitaria, ofreciendo una útil comparación con el mundo académico actual. Este capítulo se propone investigar las razones que causaron la formación de los primeros studia y las diferentes formas que estos adquirieron según el contexto histórico y cultural de los varios ambientes. Con este intento se analizan en particular dos casos: el de la Universidad de Bolina y el de la Universidad de parís.

La relación entre la actividad empresarial y los Derechos Humanos (DDHH) ha enfrentado desafíos crecientes consecuencia del crecimiento de las multinacionales, la globalización, la evolución del concepto de DDHH como herramienta política y la transformación de la gobernanza global hacia un modelo con múltiples actores. La aprobación unánime de los Principios Rectores sobre Empresas y Derechos Humanos (UNGP por sus siglas en inglés), en 2011, tras años de desacuerdos entre los distintos actores, se considera un hito histórico en relación con la búsqueda de soluciones en la cuestión de Empresa. y Derechos Humanos (BHR, por sus siglas en inglés). Esta tesis doctoral tiene como objetivo analizar la influencia de la investigación académica en el desarrollo de BHR tras la adopción de los UNGP. Para ello, se ha realizado un análisis exhaustivo del impacto y el contenido de los artículos académicos publicados sobre BHR y UNGP entre 2011 y 2019, con el fin de estructurar y mapear el conocimiento existente, así como profundizar en las aportaciones relacionadas con los aspectos fundamentales de BHR. Como resultado, se ha determinado la capacidad de impacto de los académicos en la comunidad BHR durante el período analizado. Además, se ha desarrollado una taxonomía que organiza el conocimiento de BHR en 19 grupos temáticos y se ha creado un mapa de coocurrencias que valida esta taxonomía. Se concluye que, entre 2011 y 2019, la influencia de la academia en este campo fue limitada; sin embargo, la aprobación de los UNGP dio lugar a un nuevo campo de investigación en expansión. Además, el período estudiado reveló una clara unanimidad entre los académicos respecto a la identificación de la raíz del problema, pero una notable polarización en cuanto a las soluciones.

Actualmente, los tratamientos existentes para la alergia respiratoria grave no son eficaces en todos los casos. Se desconocen los mecanismos inmunitarios que subyacen a la progresión y el mantenimiento de los fenotipos alérgicos graves. En estudios anteriores, las PBMC de pacientes alérgicos estratificados por gravedad se analizaron mediante transcriptómica, revelando alteraciones en las funciones plaquetarias. El análisis del plasma de estos pacientes mediante metabolómica reveló alteraciones en el metabolismo energético que podrían estar relacionadas con funciones alteradas de las células T. En esta Tesis, el objetivo es comprender los mecanismos biológicos relacionados con las plaquetas y las células T de pacientes alérgicos estratificados por gravedad. Mediante plaquetoféresis, el fenotipado plaquetario de pacientes alérgicos estratificados se realizó mediante lipidómica, transcriptómica y cuantificación de proteínas. Las plaquetas de pacientes alérgicos graves mostraron niveles elevados de ceramidas, fosfoinositoles, fosfocolinas y esfingomielinas. Por el contrario, mostraron niveles reducidos de precursores de eicosanoides. RNAseq confirmó la sobreexpresión de ARNm de genes relacionados con la activación plaquetaria y el metabolismo del ácido araquidónico en los fenotipos graves. El análisis de rutas biológicas indicó la alteración de las vías NOD, MAPK, TLR, TNF e IL-17 en el fenotipo grave. Las proteínas P-Selectina e IL-17AF aumentaron en el fenotipo grave. Los resultados mostraron que las plaquetas de pacientes alérgicos graves son una fuente de lípidos proinflamatorios y presentan marcadores de transcripción y proteínas relacionados con una alta activación plaquetaria. Además, las células T de los mismos pacientes fueron fenotipadas mediante transcriptómica. Los pacientes alérgicos graves presentaron una regulación negativa de los genes relacionados con la fosforilación oxidativa, la oxidación de ácidos grasos y la glucólisis junto con una mayor expresión de genes que codifican citoquinas inflamatorias. Además, la regulación negativa de los genes implicados en la vía del TGFβ junto con una tendencia disminuida en el porcentaje de células T reguladoras, sugiere una función reguladora comprometida en pacientes asmáticos alérgicos graves. En conjunto, los resultados obtenidos muestran que los pacientes alérgicos graves presentan alteraciones plaquetarias y de células T, lo que ofrece nuevas vías para la exploración de biomarcadores para identificar a los pacientes alérgicos graves y allana el camino para el desarrollo de tratamientos personalizados para estos pacientes que actualmente carecen de terapias eficaces

Chronic rhinosinusitis (CRS) is a clinical syndrome defined by typical sinonasal symptoms persisting for at least 12weeks. CRS is divided into two distinct phenotypes, CRS with nasal polyps (CRSwNP) and without (CRSsNP). The aim of the review is to provide an update on the current knowledge in CRS endotypes. The prevailing hypothesis regarding the pathogenesis of CRS suggests that dysfunctional interactions between the host and environmental stressors at the mucosal surface drive the diverse inflammatory mechanisms. Genetic and epigenetic variations in the mucosal immune system are believed to play a significant role in the pathomechanisms of CRS. Various environmental agents (such as microbes and irritants) have been implicated in CRS. In a healthy state, the sinonasal mucosa acts as a barrier, modulating environmental stimulation and mounting appropriate immune responses against pathogens with minimal tissue damage. Different endotypes may exist based on the specific mechanistic pathways driving the chronic tissue inflammation of CRS. There is a need to understand endotypes in order to better predict, diagnose, and treat CRS. This literature review provides an update on the role of the endotypes in CRS and the limitations of endotyping CRS in clinical practice. Understanding of the pathogenesis and optimal management of CRS has progressed significantly in the last decades; however, there still are several unmet needs in endotype research.