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The integration of Wide Bandgap (WBG) semiconductors has enhanced the performance of switching power supplies in terms of both efficiency and power density. However, the fast-switching dynamics of these devices, particularly in Gallium Nitride (GaN) semiconductors, amplify the impact of parasitic elements in the circuit, demanding new methods and tools in power converter design. To address this problem, a multi-objective design method for a GaN-based isolated DC-DC converter is presented, complemented by an analytical Double Pulse Test (DPT) model. This method is applied to select the optimal components and switching frequency for a push-pull converter, resulting in the design of a GaN-based step-up DC-DC converter. The analytical estimations for power losses and overvoltage are validated through a GaN-based push-pull prototype. The design achieves an efficiency of 93% under nominal conditions, with a power density of 2.23 W/cm3, and a total component cost of 17.5 € for the magnetics, capacitors, and semiconductors. This approach not only demonstrates significant improvement in terms of efficiency, volume, and cost compared to silicon-based isolated DC-DC converters but also offers a promising design methodology to improve isolated DC-DC converters in modern power conversion applications.

Priorities and programmes in the City of Cape Town’s Integrated Development Plan (2022–2027) demonstrate progress towards operationalising local level planning for climate-resilient development. These developments provide lessons of process and focus on transformative outcomes for cities seeking equitable and just development while implementing climate change adaptation and mitigation.

Drug and target discovery for advanced liver disease are hampered by a lack of suitable models for clinical translation. Here the authors present a human liver cell-based system modeling a clinical prognostic signature allowing to propose nizatidine for treatment of advanced liver fibrosis and hepatocellular carcinoma prevention.

In humans, a single enzyme 2-aminoadipic semialdehyde synthase (AASS) catalyses the initial two critical reactions in the lysine degradation pathway. This enzyme evolved to be a bifunctional enzyme with both lysine-2-oxoglutarate reductase (LOR) and saccharopine dehydrogenase domains (SDH). Moreover, AASS is a unique drug target for inborn errors of metabolism such as glutaric aciduria type 1 that arise from deficiencies downstream in the lysine degradation pathway. While work has been done to elucidate the SDH domain structurally and to develop inhibitors, neither has been done for the LOR domain. Here, we purify and characterize LOR and show that it is activated by alkylation of cysteine 414 by N-ethylmaleimide. We also provide evidence that AASS is rate-limiting upon high lysine exposure of mice. Finally, we present the crystal structure of the human LOR domain. Our combined work should enable future efforts to identify inhibitors of this novel drug target.

La adquisición de competencias digitales en las personas jóvenes sigue siendo un desafío educativo y, en este sentido, el ocio y tiempo libre (OyTL) se presenta como un ámbito formativo a explorar. Esta investigación analiza la percepción que tienen las personas jóvenes sobre sus competencias digitales en el ámbito del OyTL mediante un estudio descriptivo y correlacional con la finalidad de valorar su implementación en los programas de OyTL. La competencia digital se mide a través de un cuestionario diseñado ad hoc con cinco dimensiones relacionadas con el Marco Europeo de Competencias Digitales (DigComp) –alfabetización en información y datos, comunicación y colaboración, creación de contenido digital, resolución de problemas y seguridad –materializadas en 33 ítems, y tres variables atributivas– tipo de participante, sexo y edad. La muestra es de 947 jóvenes de diferentes partes de España: 376 vinculados a cursos de monitor de OyTL –formadores o alumnado–, y 571 no vinculados. El análisis evidencia una covarianza significativa y directa entre las cinco competencias digitales del proyecto DigComp en el OyTL. Especialmente, la competencia relacionada con la seguridad muestra resultados significativos según tipo de participante, sexo y edad. Se presenta una formación en el OyTL que favorece la adquisición de competencias digitales y compensa deficiencias formativas en otros ámbitos educativos.

Objetivo: Mostrar las raíces teóricas del conectivismo en las principales teorías históricas sobre la adquisición de conocimiento y el aprendizaje, ya que se trata del paradigma educativo más útil para entender el aprendizaje en la era digital y los procesos de e-learning. Método: Se realiza una exhaustiva recopilación de fuentes originales pertinentes, seleccionadas en base a su relevancia y significado dentro de cada corriente teórica. A través de esta revisión se presenta al conectivismo como una evolución respecto a las escuelas anteriores y no una revolución teórica en el ámbito pedagógico. Se valora al Psicoanálisis y la Escuela de la Gestalt como antecedentes más remotos y se considera la influencia del Instruccionismo, Constructivismo, Teoría del Caos, Neurociencia, Teoría de redes y Sistemas Adaptativos Complejos como referentes directos. Se continúa con el análisis de las influencias recibidas por las distintas escuelas teóricas coetáneas y actuales, como la Teoría de la Conversación, la Teoría del Actor-Red, la Red de aprendizaje (Network Learning), e-learning 2.0., Microlearning, Nano-learning, Universidad 2.0., Currículum 2.0., Pedagogía 2.0., y el Navegacionismo, para completar los fundamentos teóricos sobre los que se apoya el Conectivismo. Conclusión y discusión: Se confirman las conexiones teóricas del conectivismo con las teorías expuestas y se pronostica cada vez mayor relevancia en el ámbito educativo de este paradigma por su adecuación a la realidad social actual.

La satisfacción corporal y vital está íntimamente relacionadas durante la juventud y edad adulta. No obstante, en la vejez ambos procesos padecen severas transformaciones de forma aislada que podrían modificar la naturaleza de esta relación significativamente. Este estudio se plantea evaluar si la relación entre satisfacción corporal y vejez se mantiene estable durante la vejez y cuáles son los factores que determinan la naturaleza de dicha relación, valorando la edad, el sexo, la presencia de pareja y el entorno como variables de estudio. Se utiliza el Body Shape Questionnaire (BSQ. Cooper, Taylor, Cooper, y Fairburn, 1987, adaptado y validado sobre población española por Raich et al., 1996) para medir la satisfacción corporal, y el Cuestionario de satisfacción Vital (CSV. Sánchez, 2012) para medir la satisfacción vital. Los resultados indican que la mayor insatisfacción corporal a partir de los 65 años se asocia directamente con ser mujer, habitar en un entorno urbano y tener pareja actual. A partir de los 50 años la satisfacción corporal y vital sigue correlacionando fuertemente para las mujeres, pero las diferencias observadas según sexo están mediatizadas por la presencia de pareja, que tiene un funcionamiento inverso para hombres y mujeres, y enmascara la posible influencia del factor sexo en los participantes al estudio.

Summary: Connecting specific cancer genotypes with phenotypes and drug responses constitutes the central premise of precision oncology but is hindered by the genetic complexity and heterogeneity of primary cancer cells. Here, we use patient-derived induced pluripotent stem cells (iPSCs) and CRISPR/Cas9 genome editing to dissect the individual contributions of two recurrent genetic lesions, the splicing factor SRSF2 P95L mutation and the chromosome 7q deletion, to the development of myeloid malignancy. Using a comprehensive panel of isogenic iPSCs—with none, one, or both genetic lesions—we characterize their relative phenotypic contributions and identify drug sensitivities specific to each one through a candidate drug approach and an unbiased large-scale small-molecule screen. To facilitate drug testing and discovery, we also derive SRSF2-mutant and isogenic normal expandable hematopoietic progenitor cells. We thus describe here an approach to dissect the individual effects of two cooperating mutations to clinically relevant features of malignant diseases. : Papapetrou and colleagues develop a comprehensive panel of isogenic iPSC lines with SRSF2 P95L mutation and chr7q deletion. They use these cells to identify cellular phenotypes contributed by each genetic lesion and therapeutic vulnerabilities specific to each one and develop expandable hematopoietic progenitor cell lines to facilitate drug discovery. Keywords: induced pluripotent stem cells, myelodysplastic syndrome, CRISPR/Cas9, gene editing, mutational cooperation, splicing factor mutations, spliceosomal mutations, SRSF2, chr7q deletion

The quinolone decoquinate (DCQ) is widely used in veterinary practice for the treatment of bacterial and parasitic infections, most notably, coccidiosis in poultry and in ruminants. We have investigated the effects of treatment of Toxoplasma gondii in infected human foreskin fibroblasts (HFF) with DCQ. This induced distinct alterations in the parasite mitochondrion within 24 h, which persisted even after long-term (500 nM, 52 days) treatment, although there was no parasiticidal effect. Based on the low half-maximal effective concentration (IC50) of 1.1 nM and the high selectivity index of >5000, the efficacy of oral treatment of pregnant mice experimentally infected with T. gondii oocysts with DCQ at 10 mg/kg/day for 5 days was assessed. However, the treatment had detrimental effects, induced higher neonatal mortality than T. gondii infection alone, and did not prevent vertical transmission. Thus, three quinoline-O-carbamate derivatives of DCQ, anticipated to have better physicochemical properties than DCQ, were assessed in vitro. One such compound, RMB060, displayed an exceedingly low IC50 of 0.07 nM, when applied concomitantly with the infection of host cells and had no impact on HFF viability at 10 µM. As was the case for DCQ, RMB060 treatment resulted in the alteration of the mitochondrial matrix and loss of cristae, but the changes became apparent at just 6 h after the commencement of treatment. After 48 h, RMB060 induced the expression of the bradyzoite antigen BAG1, but TEM did not reveal any other features reminiscent of bradyzoites. The exposure of infected cultures to 300 nM RMB060 for 52 days did not result in the complete killing of all tachyzoites, although mitochondria remained ultrastructurally damaged and there was a slower proliferation rate. The treatment of mice infected with T. gondii oocysts with RMB060 did reduce parasite burden in non-pregnant mice and dams, but vertical transmission to pups could not be prevented.

Se presentan los resultados de la utilización de prácticas para prevenir o mitigar la degradación de los suelos e incrementar la captura de carbono. El estudio se desarrolló en la finca “Los Bárzaga”, en la provincia Guantánamo, donde el mal drenaje, la baja fertilidad y erosión del suelo, afectan el 90% del área, ocasionando una mayor manifestación de los procesos de degradación y disminución de los resultados productivos. Se establecieron medidas de conservación y mejoramiento de suelos atendiendo a los factores limitantes identificados y se evaluaron índices físicos y químicos además de monitorear la reserva de carbono. Las prácticas aplicadas (barreras vivas, barreras muertas, corrección de cárcavas y tranques) permitieron disminuir la pérdida de suelos en 62 t. ha-1, ocasionando cambios positivos en los índices físicos densidad aparente, velocidad de infiltración y compactación, así como en el contenido de nutrientes. Igualmente se incrementó la reserva de carbono en el suelo 20.67%.

The implementation of new practices and their results to prevent or mitigate soil degradation and increase carbon capture were presented in this paper. The study was made on "Los Barzaga" farm, in the province of Guantanamo, where poor drainage conditions, low soil fertility and erosion affect 90% of the area, causing greater degradation and reduction of production. Several soil preservation and improvement procedures were established, considering the limiting factors identified. The physical and chemical indexes were evaluated, and the carbon reserves were monitored. The practices implemented (live and dead barriers, rill and reservoir correction), contributed to a 62 t. ha-1 reduction of soil loss, with positive changes in apparent density, infiltration and compacting velocity, and nutrient contents. Additionally, soil carbon increased to 20.67%.

In the southern coastline of the province of Guantanamo, Cuba, there are communities that have lost several hectares of soil and biodiversity due to land mismanagement. "Los Cerezos" community is located in the municipality of Imias, as part of the “Eliomar Noa” UBPC (Basic Unit for Cooperated Production), which uses 99.2% of their areas for livestock raising. The land is on hills covered with xerophytic bushes; signs of degradation are clearly observed. Restoration is one alternative to revert this situation. It constitutes an effective preservation technique implemented by man to achieve optimum recovery of degraded ecosystems close to their original states. The aim of this paper is to evaluate the results achieved after recovery of local soils, using restoration techniques. Research was done in a fragmented forest, on typical red-brown fersiallitic soil, where the limiting factors were determined (rills, slopes, effective depth, organic matter content, rocks, and erosion), as well as other negative factors that may have an effect on vegetation growth. Common Ligum-vitae (Guaiacum officinalis L.) was used for reforestation due to its adaptability to the ecosystem. The restoration works helped create the conditions for progressive recovery of the areas and mitigate soil degradation, with a decrease in losses of 1 036 t. ha-1 every year, thanks to barrier accumulation.

En la zona costera Sur de la provincia Guantánamo existen comunidades en las cuales el mal manejo de sus tierras ha provocado la pérdida de numerosas hectáreas de suelo y por ende la biodiversidad de especies. Un ejemplo de esto lo constituye la comunidad ¨Los Cerezos¨, ubicada en el municipio Imías donde se encuentra enclavada la UBPC Eliomar Noa, la cual dedica el 99.2 % (1757,8 ha) de sus áreas a la ganadería, en colinas cubiertas de matorrales xerofíticos, con evidentes signos de degradación. Un método para revestir esta problemática lo constituye la restauración, el cual es considerado una técnica de conservación efectiva, para lograr mediante acciones artificiales, el ideal de recuperación de ecosistemas degradados hasta lo más cercano a las condiciones originales. El presente trabajo pretende evaluar los resultados alcanzados en la recuperación de los suelos de esta unidad a partir de técnicas de restauración. Se trabajó en un bosque fragmentado, sobre un suelo Fersialítico Pardo Rojizo Típico, donde se determinaron los factores limitantes (existencia de cárcavas, pendiente, profundidad efectiva, contenido de materia orgánica, pedregosidad y erosión) y otras afectaciones que puedan influir negativamente en el establecimiento de la vegetación, para la reforestación se utilizó el guayacán (Guaiacum officinalis L.) por su adaptabilidad al ecosistema. Las acciones de restauración permitieron crear las condiciones para la recuperación paulatina de estas áreas y mitigar la degradación de sus suelos, disminuyendo su pérdida en 1.036 t. ha-1 por año por acumulación en las barreras.

The impact of social media on teens' mental health and development raises the need for educational interventions that equip them with the knowledge and skills to cope with dangerous situations. In spite of the growing effort to expand social media literacy among youngsters, social media interventions still rely on conventional methods that tend to prioritize cognitive skills while overlooking important socio-emotional competencies. To bridge this gap and offer innovative solutions to social media education, this article presents the narrative scripts (NS) approach implemented in a learning technology environment that integrates pedagogical strategies of authentic learning, narratives, and scripted collaborative learning within a simulated educational social media platform. A longitudinal study with 370 high school students in urban schools in Barcelona (Spain) was designed to assess NS in an intervention to foster the development of social media self-protection skills. The findings demonstrated that NS supported the development of social media self-protection skills, while the students expressed positive perceptions of their overall learning experience. The intervention notably enhanced the socio-emotional competencies of responsible decision-making, self-awareness, and social awareness. This research makes a valuable contribution to the design and development of technology aimed at facilitating authentic learning experiences for social media education, with a specific focus on interventions targeting socio-emotional competencies.

Recently, we have shown that harmine induces β-cell proliferation both in vitro and in vivo, mediated via the DYRK1A-NFAT pathway. We explore structure–activity relationships of the 7-position of harmine for both DYRK1A kinase inhibition and β-cell proliferation based on our related previous structure–activity relationship studies of harmine in the context of diabetes and β-cell specific targeting strategies. 33 harmine analogs of the 7-position substituent were synthesized and evaluated for biological activity. Two novel inhibitors were identified which showed DYRK1A inhibition and human β-cell proliferation capability. The DYRK1A inhibitor, compound 1-2b, induced β-cell proliferation half that of harmine at three times higher concentration. From these studies we can draw the inference that 7-position modification is limited for further harmine optimization focused on β-cell proliferation and cell-specific targeting approach for diabetes therapeutics.

La investigación del presente trabajo está centrada en determinar el pronóstico de la demanda de potencia eléctrica en corto plazo. Para ello, se utilizó y se comparó los “perfiles de demanda” y la señal en tiempo real de la demanda eléctrica de la Empresa Eléctrica Quito S.A, EEQ, para llegar a determinar el perfil más esperado en el día. En este sentido, se utilizó el Modelo Oculto de Markov (Hidden Markov Model, HMM) para el pronóstico de la demanda en horizonte de tiempo de corto plazo. Para esto, primeramente se realizó un proceso de aprendizaje/entrenamiento al modelo con la base de datos Sistema de Información Validada Operativa, SIVO. Posteriormente, se realizó el proceso de descubrimiento de perfiles de demanda, que permitirá en pasos posteriores encontrar el perfil más esperado a ocurrir durante el día. La propuesta establece un “área de demanda esperada” que se convierte en una referencia que define el comportamiento de la demanda lo largo del día. Se realizó una evaluación en un periodo de 30 días de la metodología aplicada al sistema de la EEQ, y se observó que la herramienta acierta en un 86% de los casos y el valor de demanda en tiempo real se encuentra dentro de la banda de demanda esperada. El propósito de este trabajo es brindar una aplicación a los operadores del Sistema Nacional Interconectado, SNI, del Operador Nacional, CENACE, que permita tomar decisiones en el periodo de corto plazo optimizando los recursos de generadores existentes.

El objetivo de este estudio fue comparar el desempeño de dos test psicofísicos de sensibilidad al contraste, uno basado en un sistema informatizado - FVC 100 - y otro en láminas impresas - VCTS 6500, ambos empleando la discriminación de redes sinusoidales en condiciones de adaptación fotópica. Fueron medidos 45 ojos de 23 personas con edades entre 28 y 70 años. Los sujetos fueron reclutados en un Servicio de Oftalmología al cual concurrieron tanto por consulta como por control. A partir de tomar el criterio clínico como referencia, los resultados muestran que, de los 23 sujetos, en 16 casos ambos sistemas detectaron correctamente su estado visual, en cinco casos (10 ojos) sólo el FVC 100 consiguió hacerlo, mientras que en dos casos este sistema no detectó el problema visual y sí lo hizo el VCTS 6500. Considerando los datos obtenidos se aprecia un mejor desempeño del test informatizado, destacándose la necesidad de continuar trabajando para conseguir un atlas con información de la función de sensibilidad al contraste que considere las diferentes patologías visuales.

It has been shown that molecular interactions between site-specific chemical modifications such as acetylation and methylation on DNA-packing histones and conserved structural modules present in transcriptional proteins are closely associated with chromatin structural changes and gene activation. Unlike methyl-lysine that can interact with different protein modules including chromodomains, Tudor and MBT domains, as well as PHD fingers, acetyl-lysine (Kac) is known thus far to be recognized only by bromodomains. While histone lysine acetylation plays a crucial role in regulation of chromatin-mediated gene transcription, a high degree of sequence variation of the acetyl-lysine binding site in the bromodomains has limited our understanding of histone binding selectivity of the bromodomain family. Here, we report a systematic family-wide analysis of 14 yeast bromodomains binding to 32 lysine-acetylated peptides derived from known major acetylation sites in four core histones that are conserved in eukaryotes.The histone binding selectivity of purified recombinant yeast bromodomains was assessed by using the native core histones in an overlay assay, as well as N-terminally biotinylated lysine-acetylated histone peptides spotted on streptavidin-coated nitrocellulose membrane in a dot blot assay. NMR binding analysis further validated the interactions between histones and selected bromodomain. Structural models of all yeast bromodomains were built using comparative modeling to provide insights into the molecular basis of their histone binding selectivity.Our study reveals that while not all members of the bromodomain family are privileged to interact with acetylated-lysine, identifiable sequence features from those that bind histone emerge. These include an asparagine residue at the C-terminus of the third helix in the 4-helix bundle, negatively charged residues around the ZA loop, and preponderance of aromatic amino acid residues in the binding pocket. Further, while bromodomains exhibit selectivity for different sites in histones, individual interactions are of modest affinity. Finally, electrostatic interactions appear to be a primary determining factor that guides productive association between a bromodomain and a lysine-acetylated histone.