Alteration of the HIF-1alfa/VEGF Signalling Pathway and Disruption of the Cell Cycle by Second Generation Carbosilan Dendrimers

Current therapies against prostate cancer (PCa) disease, such as surgery, radiotherapy, or in last term chemical castration by androgen deprivation, have led to significant reduction of the incidence of PCa throughout the world. Worse prognosis found in those patients which exhibit castration resistance, relapsing into the disease with e v e n greater aggressiveness. Hypoxia cancer cell adaption has been observed to be closely connected to fatal prognostic tumor features. Therefore, hypoxia adaptive mechanisms of cancer cells have attracted large interest as a relev a n t biological target for treatment-resistant patients. Dendrimer s have been established as a promising nanotechnological tool owing to their beneficial physicochemical features such as multivalency and monodispersity. Herein, we have completed a thorough study to better understand the effect wit h i n the cel l of the already published ruthenium(II)-N-heterocyclic carbene metallodendrimer (G2Ru) that was able to drastically reduce HIF-1 alpha stabilization and exhibited antiproliferative capabi l i t y against androgen-sensitive (LNCaP) and androgen-resistant prostate cancer cells (LNFLU) in vitro. G2Ru, as well as its cationic imidazol i u m precursor (G2P), displayed scaven g i n g properties against intracellula r and externa l l y stimulated ROS levels, which would presumably hinder the stabilization of HIF-1 alpha by prolyl hydroxylase (PHD) inhibition. Furthermore, these dendrimers have shown considerably beneficial properties against tumor progression capabi l i t y in terms of apoptosis, cell cycle, CSCs expression, and epithelial phenotype promotion. Taken all together, in this study we could demonstrate the extraordinary anticancer properties of NHC-based carbosilane dendrimers against androgen-resistant prostate cancer cells in vitroInstituto de Salud Carlos IIIComunidad de MadridFundación Tatiana Pérez de Guzmán el BuenoUniversidad de AlcaláMinisterio de Economía, Industria y Competitivida

The value of desmosomal plaque-related markers to distinguish squamous cell carcinoma and adenocarcinoma of the lung

An antibody panel is needed to definitively differentiate between adenocarcinoma (AC) and squamous cell carcinoma (SCC) in order to meet more stringent requirements for the histologic classification of lung cancers. Staining of desmosomal plaque-related proteins may be useful in the diagnosis of lung SCC. The specificity for SCC of membrane staining for PKP1, KRT15, and DSG3 was 97.4%, 94.6%, and 100%, respectively, and it was 100% when the markers were used together and in combination with the conventional markers (AUCs of 0.7619 for Panel 1 SCC, 0.7375 for Panel 2 SCC, 0.8552 for Panel 1 AC, and 0.8088 for Panel 2 AC). In a stepwise multivariate logistic regression model, the combination of CK5/6, p63, and PKP1 in membrane was the optimal panel to differentiate between SCC and AC, with a percentage correct classification of 96.2% overall (94.6% of ACs and 97.6% of SCCs). PKP1 and DSG3 are related to the prognosis. PKP1, KRT15, and DSG3 are highly specific for SCC, but they were more useful to differentiate between SCC and AC when used together and in combination with conventional markers. PKP1 and DSG3 expressions may have prognostic value.MEFV was supported by PAIDI programme, Group BIO309, Junta de Andalucía

Actualización y optimización del sistema de seguimiento de egresados de la Facultad de Ciencias Matemáticas y su aplicación en la mejora de la calidad de los títulos

Resumen del proyecto PIMCD 232 (2017) que presenta el diseño y uso de un sistema de seguimiento de egresados en la Facultad de Matemáticas para análisis de empleabilidad así como para información que valga para la mejora de las titulaciones

Advances on the investigation of landslides by space-borne synthetic aperture radar interferometry

Landslides are destructive geohazards to people and infrastructure, resulting in hundreds of deaths and billions of dollars of damage every year. Therefore, mapping the rate of deformation of such geohazards and understanding their mechanics is of paramount importance to mitigate the resulting impacts and properly manage the associated risks. In this paper, the main outcomes relevant to the joint European Space Agency (ESA) and the Chinese Ministry of Science and Technology (MOST) Dragon-5 initiative cooperation project ID 59,339 “Earth observation for seismic hazard assessment and landslide early warning system” are reported. The primary goals of the project are to further develop advanced SAR/InSAR and optical techniques to investigate seismic hazards and risks, detect potential landslides in wide regions, and demonstrate EO-based landslide early warning system over selected landslides. This work only focuses on the landslide hazard content of the project, and thus, in order to achieve these objectives, the following tasks were developed up to now: a) a procedure for phase unwrapping errors and tropospheric delay correction; b) an improvement of a cross-platform SAR offset tracking method for the retrieval of long-term ground displacements; c) the application of polarimetric SAR interferometry (PolInSAR) to increase the number and quality of monitoring points in landslide-prone areas; d) the semiautomatic mapping and preliminary classification of active displacement areas on wide regions; e) the modeling and identification of landslides in order to identify triggering factors or predict future displacements; and f) the application of an InSAR-based landslide early warning system on a selected site. The achieved results, which mainly focus on specific sensitive regions, provide essential assets for planning present and future scientific activities devoted to identifying, mapping, characterizing, monitoring and predicting landslides, as well as for the implementation of early warning systems.This work was supported by the ESA-MOST China DRAGON-5 project with ref. 59339, by the Spanish Ministry of Science and Innovation, the State Agency of Research (AEI), and the European Funds for Regional Development under grant [grant number PID2020-117303GB-C22], by the Conselleria de Innovación, Universidades, Ciencia y Sociedad Digital in the framework of the project CIAICO/2021/335, by the Natural Science Foundation of China [grant numbers 41874005 and 41929001], the Fundamental Research Funds for the Central University [grant numbers 300102269712 and 300102269303], and China Geological Survey Project [grant numbers DD20190637 and DD20190647]. Xiaojie Liu and Liuru Hu have been funded by Chinese Scholarship Council Grants Ref. [grant number 202006560031] and [grant number 202004180062], respectively

Estrategias de publicidad social. Coyunturas sociales como oportunidad de mejoramiento de valor responsable

Este libro invita a un grupo de autores, pertenecientes a tres grupos de investigación de distintas universidades, a enriquecer la reflexión sobre el papel que desempeña la publicidad social en las estrategias de responsabilidad social empresarial y cómo esto puede redundar en el mejoramiento del valor de marca. Las apreciaciones se encuadran en el escenario de posguerra o posconflicto que vive el País desde la firma de los Acuerdos de la Habana, entre el Estado colombiano y las FARC-EP

Inquiry in University Mathematics Teaching and Learning. The Platinum Project

The book presents developmental outcomes from an EU Erasmus+ project involving eight partner universities in seven countries in Europe. Its focus is the development of mathematics teaching and learning at university level to enhance the learning of mathematics by university students. Its theoretical focus is inquiry-based teaching and learning. It bases all activity on a three-layer model of inquiry: (1) Inquiry in mathematics and in the learning of mathematics in lecture, tutorial, seminar or workshop, involving students and teachers; (2) Inquiry in mathematics teaching involving teachers exploring and developing their own practices in teaching mathematics; (3) Inquiry as a research process, analysing data from layers (1) and (2) to advance knowledge inthe field. As required by the Erasmus+ programme, it defines Intellectual Outputs (IOs) that will develop in the project. PLATINUM has six IOs: The Inquiry-based developmental model; Inquiry communities in mathematics learning and teaching; Design of mathematics tasks and teaching units; Inquiry-based professional development activity; Modelling as an inquiry process; Evalutation of inquiry activity with students. The project has developed Inquiry Communities, in each of the partner groups, in which mathematicians and educators work together in supportive collegial ways to promote inquiry processes in mathematics learning and teaching. Through involving students in inquiry activities, PLATINUM aims to encourage students‘ own in-depth engagement with mathematics, so that they develop conceptual understandings which go beyond memorisation and the use of procedures. Indeed the eight partners together have formed an inquiry community, working together to achieve PLATINUM goals within the specific environments of their own institutions and cultures. Together we learn from what we are able to achieve with respect to both common goals and diverse environments, bringing a richness of experience and learning to this important area of education. Inquiry communities enable participants to address the tensions and issues that emerge in developmental processes and to recognise the critical nature of the developmental process. Through engaging in inquiry-based development, partners are enabled and motivated to design activities for their peers, and for newcomers to university teaching of mathematics, to encourage their participation in new forms of teaching, design of teaching, and activities for students. Such professional development design is an important outcome of PLATINUM. One important area of inquiry-based activity is that of „modelling“ in mathematics. Partners have worked together across the project to investigate the nature of modelling activities and their use with students. Overall, the project evaluates its activity in these various parts to gain insights to the sucess of inquiry based teaching, learning and development as well as the issues and tensions that are faced in putting into practice its aims and goals

Inquiry in University Mathematics Teaching and Learning

The book presents developmental outcomes from an EU Erasmus+ project involving eight partner universities in seven countries in Europe. Its focus is the development of mathematics teaching and learning at university level to enhance the learning of mathematics by university students. Its theoretical focus is inquiry-based teaching and learning. It bases all activity on a three-layer model of inquiry: (1) Inquiry in mathematics and in the learning of mathematics in lecture, tutorial, seminar or workshop, involving students and teachers; (2) Inquiry in mathematics teaching involving teachers exploring and developing their own practices in teaching mathematics; (3) Inquiry as a research process, analysing data from layers (1) and (2) to advance knowledge inthe field. As required by the Erasmus+ programme, it defines Intellectual Outputs (IOs) that will develop in the project. PLATINUM has six IOs: The Inquiry-based developmental model; Inquiry communities in mathematics learning and teaching; Design of mathematics tasks and teaching units; Inquiry-based professional development activity; Modelling as an inquiry process; Evalutation of inquiry activity with students. The project has developed Inquiry Communities, in each of the partner groups, in which mathematicians and educators work together in supportive collegial ways to promote inquiry processes in mathematics learning and teaching. Through involving students in inquiry activities, PLATINUM aims to encourage students` own in-depth engagement with mathematics, so that they develop conceptual understandings which go beyond memorisation and the use of procedures. Indeed the eight partners together have formed an inquiry community, working together to achieve PLATINUM goals within the specific environments of their own institutions and cultures. Together we learn from what we are able to achieve with respect to both common goals and diverse environments, bringing a richness of experience and learning to this important area of education. Inquiry communities enable participants to address the tensions and issues that emerge in developmental processes and to recognise the critical nature of the developmental process. Through engaging in inquiry-based development, partners are enabled and motivated to design activities for their peers, and for newcomers to university teaching of mathematics, to encourage their participation in new forms of teaching, design of teaching, and activities for students. Such professional development design is an important outcome of PLATINUM. One important area of inquiry-based activity is that of “modelling” in mathematics. Partners have worked together across the project to investigate the nature of modelling activities and their use with students. Overall, the project evaluates its activity in these various parts to gain insights to the sucess of inquiry based teaching, learning and development as well as the issues and tensions that are faced in putting into practice its aims and goals

The evolution of the ventilatory ratio is a prognostic factor in mechanically ventilated COVID-19 ARDS patients

Background: Mortality due to COVID-19 is high, especially in patients requiring mechanical ventilation. The purpose of the study is to investigate associations between mortality and variables measured during the first three days of mechanical ventilation in patients with COVID-19 intubated at ICU admission. Methods: Multicenter, observational, cohort study includes consecutive patients with COVID-19 admitted to 44 Spanish ICUs between February 25 and July 31, 2020, who required intubation at ICU admission and mechanical ventilation for more than three days. We collected demographic and clinical data prior to admission; information about clinical evolution at days 1 and 3 of mechanical ventilation; and outcomes. Results: Of the 2,095 patients with COVID-19 admitted to the ICU, 1,118 (53.3%) were intubated at day 1 and remained under mechanical ventilation at day three. From days 1 to 3, PaO2/FiO2 increased from 115.6 [80.0-171.2] to 180.0 [135.4-227.9] mmHg and the ventilatory ratio from 1.73 [1.33-2.25] to 1.96 [1.61-2.40]. In-hospital mortality was 38.7%. A higher increase between ICU admission and day 3 in the ventilatory ratio (OR 1.04 [CI 1.01-1.07], p = 0.030) and creatinine levels (OR 1.05 [CI 1.01-1.09], p = 0.005) and a lower increase in platelet counts (OR 0.96 [CI 0.93-1.00], p = 0.037) were independently associated with a higher risk of death. No association between mortality and the PaO2/FiO2 variation was observed (OR 0.99 [CI 0.95 to 1.02], p = 0.47). Conclusions: Higher ventilatory ratio and its increase at day 3 is associated with mortality in patients with COVID-19 receiving mechanical ventilation at ICU admission. No association was found in the PaO2/FiO2 variation