On the circulation and the position of the forward stagnation point on airfoils

Lift and velocity circulation around airfoils are two aspects of the same phenomenon when airfoils are not stalled and the Kutta—Joukowski theorem applies. This theorem establishes a linear dependence between lift and circulation, which breaks when stalling occurs. As the angle of attack increases beyond this point, the circulation vanishes. Since the circulation determines to a great extent the position of the forward stagnation point on an airfoil, the measurement of this position is an easy and simple way to determine the circulation, which is of help in understanding the role of the latter in the generation of aerodynamic forces on airfoils

Diseño de Vivienda de Interés Social Destinada a Familias de Nivel Socioeconómico I y II Ubicadas en el Área Rural del Municipio de Cachipay Cundinamarca

Realizar el diseño de una vivienda de interés social destinada a las familias de clase baja ubicadas en el área rural del municipio de Cachipay Cundinamarca, reduciendo los costos de construcción mediante el uso de materiales industrializados.Colombia es un territorio en el que se tiene presencia de diversos grupos poblacionales situados principalmente en las grandes ciudades y cabeceras municipales. En la zona rural se tiene menor proporción de habitantes, donde un alto porcentaje corresponde a familias de clase baja de estrato socioeconómico 1 y 2 teniendo la mayor presencia de problemas de deficiencia en la calidad de vivienda que influye directamente en la calidad de vida de las familias. La baja capacidad económica, la dificultad e incremento de los costos de los materiales por encontrarse lejos de los lugares de producción y la falta de conocimiento y asesoramiento técnico y profesional en el desarrollo de las construcciones, son las razones principales de la deficiencia en la calidad de las construcciones encontradas en el área de enfoque Aunque se tenga identificada las principales causas, la forma en la que a través de los años se ha enfrentado esta situación es deficienteColombia is a territory with diverse population groups located mainly in large cities and municipal capitals.The rural area has a smaller proportion of inhabitants, where a high percentage of low-class families of socioeconomic stratum 1 and 2, with the greatest presence of deficiency problems in the quality of housing that directly influences the quality of life of the families. The low economic capacity, the increase in the cost of materials, the difficulty of accessing them because they are located far from the places of production, the lack of knowledge and technical and professional advice in the development of the constructions, are the main reasons for the deficiency in the quality of the constructions found in the focus area. Although the main causes have been identified, the way in which this situation has been faced over the years is deficien

Interacción con la Música Flamenca: Análisis y Generación

One main concern in Europe is the preservation and promotion of cultural heritage. Music is a main component of such heritage and flamenco is a main part of Andalusian musical culture. Focusing on flamenco music, in this paper, we describe steps on the analysis and generation of flamenco music oriented towards the diffusion and promotion of this musical style. Specifically, the separation of meaningful musical audio elements from flamenco excerpts by means of the scheme that will be described provides a novel an interactive way of listening to flamenco music by enabling the user to select or emphasize audio elements at will. Also, the scheme for the interactive generation of flamenco music that will be presented allows the user to play and interact with flamenco music by means of a user friendly interface implemented for iOS devices.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech. Ese trabajo ha sido parcialmente financiado por Campus de Excelencia Internacional en Patrimonio, PATRIMONIUN-10, para programas de generación de investigación de referencia internacional en materia de Patrimonio Cultural y Natural, convocatoria realizada en el ámbito del proyecto PATRIMONIUN-10, Jaén, Marzo de 2014, y por el Ministerio de Economía y Competitividad del Gobierno de España, Proyecto TIN2013-47276-C6-2-R

Clinical and molecular characterization of a cardiac ryanodine receptor founder mutation causing catecholaminergic polymorphic ventricular tachycardia

Background Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a difficult-to-diagnose cause of sudden cardiac death (SCD). We identified a family of 1400 individuals with multiple cases of CPVT, including 36 SCDs during youth. Objectives We sought to identify the genetic cause of CPVT in this family, to preventively treat and clinically characterize the mutation-positive individuals, and to functionally characterize the pathogenic mechanisms of the mutation. Methods Genetic testing was performed for 1404 relatives. Mutation-positive individuals were preventively treated with β-blockers and clinically characterized with a serial exercise treadmill test (ETT) and Holter monitoring. In vitro functional studies included caffeine sensitivity and store overload–induced calcium release activity of the mutant channel in HEK293 cells. Results We identified the p.G357S_RyR2 mutation, in the cardiac ryanodine receptor, in 179 family members and in 6 SCD cases. No SCD was observed among treated mutation-positive individuals over a median follow-up of 37 months; however, 3 relatives who had refused genetic testing (confirmed mutation-positive individuals) experienced SCD. Holter monitoring did not provide relevant information for CPVT diagnosis. One single ETT was unable to detect complex cardiac arrhythmias in 72% of mutation-positive individuals, though the serial ETT improved the accuracy. Functional studies showed that the G357S mutation increased caffeine sensitivity and store overload–induced calcium release activity under conditions that mimic catecholaminergic stress. Conclusion Our study supports the use of genetic testing to identify individuals at risk of SCD to undertake prophylactic interventions. We also show that the pathogenic mechanisms of p.G357S_RyR2 appear to depend on β-adrenergic stimulation

Experiencia docente universitaria mediante el uso de metodologías activas para el aprendizaje como la evaluación formativa compartida y el trabajo de competencias transversales

[EN] This work shows an active methodology for university teaching through cooperative learning and learning assessment conducted through the collaborative formative assessment, all mediated by the transversal skills of teamwork and communicative of public speaking. The research methodology consisted of comparing the marks obtained in the same subject prior to implement the cooperative learning and collaborative formative assessment with the ones obtained after their use. The results show that the use of tools of cooperative learning and participatory and formative assessment originate better learning in students in relation to older and more traditional teaching-learning and assessment methods, also increases their involvement and learning, taken advantage of those to further enhance their skills of teamwork and public speaking communication.[ES] Este trabajo muestra una metodología activa para la enseñanza universitaria a través del aprendizaje cooperativo y la evaluación de los aprendizajes realizada a través de la evaluación formativa compartida, todo ello vehiculizado con las competencias transversales de trabajo en equipo y comunicativa de hablar en público.La metodología de investigación ha consistido en comparar las calificaciones obtenidas en la misma asignatura con anterioridad a implementar el aprendizaje cooperativo y la evaluación compartida formativa, con las obtenidas después de utilizarla. Los resultados demuestran que la utilización de herramientas de aprendizaje cooperativo y de evaluación participativa y formativa originan un mejor aprendizaje en el alumnado en relación a metodologías más antiguas y tradicionales de enseñanza-aprendizaje y evaluación, esta nueva metodología aumenta su implicación y aprendizaje, la cual se aprovecha para potenciar asimismo sus competencias de trabajo en equipo y comunicativa de hablar en público.Trigueros Preciados, S.; Perez Gonzalez, D.; Solana González, P.; García Ruiz, E. (2016). Experiencia docente universitaria mediante el uso de metodologías activas para el aprendizaje como la evaluación formativa compartida y el trabajo de competencias transversales. En In-Red 2016. II Congreso nacional de innovación educativa y docencia en red. Editorial Universitat Politècnica de València. https://doi.org/10.4995/INRED2016.2016.4351OC

Plasma Concentrations of Neurofilament Light Chain Protein and Brain-Derived Neurotrophic Factor as Consistent Biomarkers of Cognitive Impairment in Alcohol Use Disorder

For a long time, Substance Use Disorders (SUDs) were not considered a component in the etiology of dementia. The fifth edition of the Diagnostic and Statistical Manual of Mental Disorders introduced substance-induced neurocognitive disorders, incorporating this notion to clinical practice. However, detection and monitoring of neurodegenerative processes in SUD patients remain a major clinical challenge, especially when early diagnosis is required. In the present study, we aimed to investigate new potential biomarkers of neurodegeneration that could predict cognitive impairment in SUD patients: the circulating concentrations of Neurofilament Light chain protein (NfL) and Brain-Derived Neurotrophic Factor (BDNF). Sixty SUD patients were compared with twenty-seven dementia patients and forty healthy controls. SUD patients were recruited and assessed using the Psychiatric Research Interview for Substance and Mental (PRISM) and a battery of neuropsychological tests, including the Montreal Cognitive Assessment test for evaluation of cognitive impairment. When compared to healthy control subjects, SUD patients showed increases in plasma NfL concentrations and NfL/BDNF ratio, as well as reduced plasma BDNF levels. These changes were remarkable in SUD patients with moderate–severe cognitive impairment, being comparable to those observed in dementia patients. NfL concentrations correlated with executive function and memory cognition in SUD patients. The parameters “age”, “NfL/BDNF ratio”, “first time alcohol use”, “age of onset of alcohol use disorder”, and “length of alcohol use disorder diagnosis” were able to stratify our SUD sample into patients with cognitive impairment from those without cognitive dysfunction with great specificity and sensibility. In conclusion, we propose the combined use of NfL and BDNF (NfL/BDNF ratio) to monitor substance-induced neurocognitive disorder.Instituto de Salud Carlos III (ISCIII], Ministerio de Ciencia e Innovación and European Regional Development Funds-European Union (ERDF-EU] grants “Proyectos de Investigación en Salud” PI19/01577, PI19/00886, PI20/01399 and PI22/00427; Grants Programa RICORS RIAPAD (Red de Investigación en Atención Primaria en Adicciones), Programa RETICS Red de Trastornos Adictivos, (RD16/0017/000); Ministerio de Sanidad, Delegación de Gobierno para el Plan Nacional sobre Drogas (PND 2022I020, PND2020/048, PND 2019/040]; Consejería de Salud y Familia, Junta de Andalucía (Neuro-RECA, RIC-0111-2019]. FJP (CPII19/00022] and AS (CPII19/00031] hold “Miguel Servet II” research contracts from the National System of Health, ISCIII, ERDF-EU. FJP also holds a “Nicolas Monardes” contract from Servicio Andaluz de Salud, Consejería de Salud y Familia, Junta de Andalucía (C1-0049-2019]. PA has a research contract (UMA-FEDERJA-076) funded by the Ministry of Economy and Knowledge—Regional Government of Andalucía and ERDF-EU. The funding sources had no further role in the study design; in the collection, analysis, and interpretation of data; in writing of the report; or in the decision to submit the paper for publication

Impact of prophylactic TNF blockade in the dual PD-1 and CTLA-4 immunotherapy efficacy and toxicity

The TNF blockade therapy is currently a well-established treatment option for a variety of autoimmune diseases such as rheumatoid arthritis (RA), psoriasis or Crohn's disease, given the proinflammatory role of TNF in the course of these diseases. Importantly, TNF neutralization is also used for the treatment of corticosteroid-refractory immune-related adverse events (irAEs) induced by the combined anti-PD-1 and anti-CTLA-4 immunotherapy. The manifestation of these toxicities is an important limiting factor for the successful implementation of the inhibitory checkpoint blockade therapy (ICB), restraining its anti-tumor efficacy. In our recent study (Perez-Ruiz et al., Nature 569(7756): 428-432.), we analyzed the potential impact of prophylactic TNF neutralization therapy in the anti-PD1/CTLA-4 efficacy. Through several mouse models, we demonstrated that TNF neutralization ameliorated ICB-exacerbated colitis in addition to improving ICB-dependent anti-tumor efficacy. Similar results were obtained after prophylactic TNF blockade in graft vs host xenografted mouse models with human immune cells, which showed a reduction in colitis and hepatitis. Importantly, there was a preservation of the immunotherapeutic control of xenografted tumors after ICB treatment. Moreover, TNF and TNF-dependent gene expression is upregulated in the colon mucosa from patients affected by colitis as a side effect of ipilimumab and nivolumab. Our results, thus, provide evidence of the successful combination of prophylactic TNF neutralization with ICB therapy strategy to ameliorate toxicities, while keeping or even ameliorating anti-tumor efficacy. The prophylactic TNF blockade strategy is clinically feasible since excellent TNF inhibitors have been approved for the treatment of autoimmunity and are used for the immune-related serious adverse events in immunotherapy

Construction, purification, and characterization of a chimeric TH1 antagonist

BACKGROUND: TH1 immune response antagonism is a desirable approach to mitigate some autoimmune and inflammatory reactions during the course of several diseases where IL-2 and IFN-γ are two central players. Therefore, the neutralization of both cytokines could provide beneficial effects in patients suffering from autoimmune or inflammatory illnesses. RESULTS: A chimeric antagonist that can antagonize the action of TH1 immunity mediators, IFN-γ and IL-2, was designed, engineered, expressed in E. coli, purified and evaluated for its in vitro biological activities. The TH1 antagonist molecule consists of the extracellular region for the human IFNγ receptor chain 1 fused by a four-aminoacid linker peptide to human 60 N-terminal aminoacid residues of IL-2. The corresponding gene fragments were isolated by RT-PCR and cloned in the pTPV-1 vector. E. coli (W3110 strain) was transformed with this vector. The chimeric protein was expressed at high level as inclusion bodies. The protein was partially purified by pelleting and washing. It was then solubilized with strong denaturant and finally refolded by gel filtration. In vitro biological activity of chimera was demonstrated by inhibition of IFN-γ-dependent HLA-DR expression in Colo 205 cells, inhibition of IFN-γ antiproliferative effect on HEp-2 cells, and by a bidirectional effect in assays for IL-2 T-cell dependent proliferation: agonism in the absence versus inhibition in the presence of IL-2. CONCLUSION: TH1 antagonist is a chimeric protein that inhibits the in vitro biological activities of human IFN-γ, and is a partial agonist/antagonist of human IL-2. With these attributes, the chimera has the potential to offer a new opportunity for the treatment of autoimmune and inflammatory diseases