18 research outputs found

    Tunable magnetocaloric effect around room temperature by Fe doping in Mn0.98Cr(0.02-x)FexAs compound

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    In this work, we present an investigation of the magnetic and magnetocaloric properties of Mn0.98Cr(0.02-x)FexAs compounds with x = 0.002, 0.005 and 0.010. Our findings show that as Fe content increases the unit cell volume decreases, which indicates that Fe doping emulates the pressure effect on the crystalline structure. The transition temperature TC decreases as x increases and it can be set at approximate value of room temperature by changing the doping level. In addition, the magnetic entropy change ΔSM was determined using a discontinuous measurement protocol, and realistic values from the magnetocaloric effect presented by MnAs-type compounds under pressure (emulated pressure) could be obtained. The values of ΔSMMAX are very large, around −11 Jkg−1K−1 with ΔH = 15 kOe, which is higher than that observed for most compounds with TC around room temperature. However, ΔSM is confined to a narrow temperature range of 11 K. To overcome this drawback, the composition of a theoretical composite formed by our samples was calculated in order to obtain a table-shaped ΔSM curve. The simulated composite showed a high value of full width at half maximum δTFWHM of 33 K, which is much higher than that of single sample.Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro - FAPERJ E-26/110.393/2014, E-16/210.263/2014Coordenação de aperfeiçoamento de pessoal de nivel superior - CAPES 485200/2013-9Fundación de Apoyo a la Investigación del Estado de São Paulo - FAPESP 2012/03480-0Ministerio de Economía y Competitividad MAT2013-45165-

    Adoptive NK cell transfer as a treatment in colorectal cancer patients: analyses of tumour cell determinants correlating with efficacy in vitro and in vivo

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    6 figures.-- Supplementary material available.Background: Colorectal cancer (CRC) is a heterogeneous disease with variable mutational profile and tumour microenvironment composition that influence tumour progression and response to treatment. While chemoresistant and poorly immunogenic CRC remains a challenge, the development of new strategies guided by biomarkers could help stratify and treat patients. Allogeneic NK cell transfer emerges as an alternative against chemoresistant and poorly immunogenic CRC.Methods: NK cell-related immunological markers were analysed by transcriptomics and immunohistochemistry in human CRC samples and correlated with tumour progression and overall survival. The anti-tumour ability of expanded allogeneic NK cells using a protocol combining cytokines and feeder cells was analysed in vitro and in vivo and correlated with CRC mutational status and the expression of ligands for immune checkpoint (IC) receptors regulating NK cell activity.Results: HLA-I downmodulation and NK cell infiltration correlated with better overall survival in patients with a low-stage (II) microsatellite instability-high (MSI-H) CRC, suggesting a role of HLA-I as a prognosis biomarker and a potential benefit of NK cell immunotherapy. Activated allogeneic NK cells were able to eliminate CRC cultures without PD-1 and TIM-3 restriction but were affected by HLA-I expression. In vivo experiments confirmed the efficacy of the therapy against both HLA+ and HLA− CRC cell lines. Concomitant administration of pembrolizumab failed to improve tumour control.Conclusions: Our results reveal an immunological profile of CRC tumours in which immunogenicity (MSI-H) and immune evasion mechanisms (HLA downmodulation) favour NK cell immunosurveillance at early disease stages. Accordingly, we have shown that allogeneic NK cell therapy can target tumours expressing mutations conferring poor prognosis regardless of the expression of T cell-related inhibitory IC ligands. Overall, this study provides a rationale for a new potential basis for CRC stratification and NK cell-based therapy.Work in the JP laboratory is funded by ASPANOA, CIBER (CB 2021; Instituto de Salud Carlos III, Ministerio de Ciencia, Innovación and Union Europea.NextGenerationEU), Fundacion Inocente, Carrera de la Mujer Monzón, FEDER/Gobierno de Aragón (Group B29_17R), and Ministerio de Ciencia, Innovación e Universidades (MCNU), Agencia Estatal de Investigación (SAF2017‐83120‐C2‐1‐R and PID2020-113963RB-I00). Predoctoral grants/contracts from Gobierno de Aragon (IU-M and JP) are supported by ARAID Foundation. EG is funded by Ministerio de Ciencia, Innovación y Universidades (MCNU), and Agencia Estatal de Investigación (PID2020-113963RB-I00). MA and LS are funded by Postdoctoral Juan de la Cierva Contract. SR, LC, SH, and IU-M are funded by predoctoral contracts from Aragon Government. PL is funded by FPU predoctoral grants from Ministerio de Ciencia, Innovación e Universidades. Work at the Catalan Institute of Oncology is funded by the entity, the Instituto de Salud Carlos III and Ministerio de Economia y Competitividad, and co-funded by FEDER funds—a way to build Europe (PI20/00767), CIBERESP (grant CB07/02/2005), H2020 grant MoTriColor, and the Agency for Management of University and Research Grants (AGAUR) of the Catalan Government grant 2017SGR723. This work is supported by COST Action CA17118.Peer reviewe

    ¿Qué queda de mí?

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    Este libro es una reclamación a quienes hemos sido, somos o seremos docentes. A quienes no hemos respetado a las personas que se han puesto junto a nosotros y nosotras, confiando su bien más preciado: la libertad. Estas páginas denuncian cada vez que convertimos una visión en la visión, una emoción en la emoción, un saber en el saber, un comportamiento en el comportamiento. Es un grito contra la imposición, la normalización, la neutralización y la universalización de una perspectiva particular. Una pugna contra cada proceso que no se ha conectado con las vidas de los aprendices. Un texto colaborativo realizado por alumnado de Educación y Cambio Social en el Grado en Educación Infantil de la Universidad de Málaga y coordinado por Ignacio Calderón Almendros

    A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

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    La renovación de la palabra en el bicentenario de la Argentina : los colores de la mirada lingüística

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    El libro reúne trabajos en los que se exponen resultados de investigaciones presentadas por investigadores de Argentina, Chile, Brasil, España, Italia y Alemania en el XII Congreso de la Sociedad Argentina de Lingüística (SAL), Bicentenario: la renovación de la palabra, realizado en Mendoza, Argentina, entre el 6 y el 9 de abril de 2010. Las temáticas abordadas en los 167 capítulos muestran las grandes líneas de investigación que se desarrollan fundamentalmente en nuestro país, pero también en los otros países mencionados arriba, y señalan además las áreas que recién se inician, con poca tradición en nuestro país y que deberían fomentarse. Los trabajos aquí publicados se enmarcan dentro de las siguientes disciplinas y/o campos de investigación: Fonología, Sintaxis, Semántica y Pragmática, Lingüística Cognitiva, Análisis del Discurso, Psicolingüística, Adquisición de la Lengua, Sociolingüística y Dialectología, Didáctica de la lengua, Lingüística Aplicada, Lingüística Computacional, Historia de la Lengua y la Lingüística, Lenguas Aborígenes, Filosofía del Lenguaje, Lexicología y Terminología

    Plantillas personalizadas desde el smartphone

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    El Instituto de Biomecánica (IBV) ha desarrollado SUNfeet, unas plantillas confort totalmente personalizadas basadas en una tecnología puntera que combina un preciso sistema de captura de la forma del pie accesible a través de cualquier smartphone con un proceso de fabricación en impresión 3D. El resultado son unas plantillas exclusivas, a gusto del usuario, que mejoran el confort del calzad

    Regulation of androgen receptor activity by transient interactions of its transactivation domain with general transcription regulators

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    The androgen receptor is a transcription factor that plays a key role in the development of prostate cancer, and its interactions with general transcription regulators are therefore of potential therapeutic interest. The mechanistic basis of these interactions is poorly understood due to the intrinsically disordered nature of the transactivation domain of the androgen receptor and the generally transient nature of the protein-protein interactions that trigger transcription. Here, we identify a motif of the transactivation domain that contributes to transcriptional activity by recruiting the C-terminal domain of subunit 1 of the general transcription regulator TFIIF. These findings provide molecular insights into the regulation of androgen receptor function and suggest strategies for treating castration-resistant prostate cancer.This work was supported by IRB, ICREA (X.S.), Obra Social “la Caixa” (E.D.M., E.S., and X.S.), MINECO (BIO2012-31043 and BIO2015-70092-R to X.S., BIO2014-53095-P to G.D.F.), Marató de TV3 (102030 to X.S. and 102031 to E.E.-P), the COFUND program of the European Commission (C.D.S.), the European Research Council (CONCERT, contract number 648201 to X.S.), the Ramón y Cajal program of MICINN (RYC-2011-07873 to C.W.B.), the Serra Hunter Program (E.E.-P.), AGAUR (SGR-2014-56RR14 to E.E.-P), and FEDER (G.D.F.). I.H. was supported by funding from the Chief Scientist's Office of the Scottish Government (ETM-258, ETM-382). IRB Barcelona is the recipient of a Severo Ochoa Award of Excellence from MINECO (Government of Spain)

    Regulation of androgen receptor activity by transient interactions of its transactivation domain with general transcription regulators

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    The androgen receptor is a transcription factor that plays a key role in the development of prostate cancer, and its interactions with general transcription regulators are therefore of potential therapeutic interest. The mechanistic basis of these interactions is poorly understood due to the intrinsically disordered nature of the transactivation domain of the androgen receptor and the generally transient nature of the protein-protein interactions that trigger transcription. Here, we identify a motif of the transactivation domain that contributes to transcriptional activity by recruiting the C-terminal domain of subunit 1 of the general transcription regulator TFIIF. These findings provide molecular insights into the regulation of androgen receptor function and suggest strategies for treating castration-resistant prostate cancer.This work was supported by IRB, ICREA (X.S.), Obra Social “la Caixa” (E.D.M., E.S., and X.S.), MINECO (BIO2012-31043 and BIO2015-70092-R to X.S., BIO2014-53095-P to G.D.F.), Marató de TV3 (102030 to X.S. and 102031 to E.E.-P), the COFUND program of the European Commission (C.D.S.), the European Research Council (CONCERT, contract number 648201 to X.S.), the Ramón y Cajal program of MICINN (RYC-2011-07873 to C.W.B.), the Serra Hunter Program (E.E.-P.), AGAUR (SGR-2014-56RR14 to E.E.-P), and FEDER (G.D.F.). I.H. was supported by funding from the Chief Scientist's Office of the Scottish Government (ETM-258, ETM-382). IRB Barcelona is the recipient of a Severo Ochoa Award of Excellence from MINECO (Government of Spain)

    Regulation of androgen receptor activity by transient interactions of its transactivation domain with general transcription regulators

    No full text
    The androgen receptor is a transcription factor that plays a key role in the development of prostate cancer, and its interactions with general transcription regulators are therefore of potential therapeutic interest. The mechanistic basis of these interactions is poorly understood due to the intrinsically disordered nature of the transactivation domain of the androgen receptor and the generally transient nature of the protein-protein interactions that trigger transcription. Here, we identify a motif of the transactivation domain that contributes to transcriptional activity by recruiting the C-terminal domain of subunit 1 of the general transcription regulator TFIIF. These findings provide molecular insights into the regulation of androgen receptor function and suggest strategies for treating castration-resistant prostate cancer

    Clinical spectrum of COVID-19 and risk factors associated with severity in Spanish children.

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    We aimed to identify the spectrum of disease in children with COVID-19, and the risk factors for admission in paediatric intensive care units (PICUs). We conducted a multicentre, prospective study of children with SARS-CoV-2 infection in 76 Spanish hospitals. We included children with COVID-19 or multi-inflammatory syndrome (MIS-C) younger than 18 years old, attended during the first year of the pandemic. We enrolled 1200 children. A total of 666 (55.5%) were hospitalised, and 123 (18.4%) required admission to PICU. Most frequent major clinical syndromes in the cohort were mild syndrome (including upper respiratory tract infection and flu-like syndrome, skin or mucosae problems and asymptomatic), 44.8%; bronchopulmonary syndrome (including pneumonia, bronchitis and asthma flare), 18.5%; fever without a source, 16.2%; MIS-C, 10.6%; and gastrointestinal syndrome, 10%. In hospitalised children, the proportions were 28.5%, 25.7%, 16.5%, 19.1% and 10.2%, respectively. Risk factors associated with PICU admission were age in months (OR: 1.007; 95% CI 1.004 to 1.01), MIS-C (OR: 14.4, 95% CI 8.9 to 23.8), chronic cardiac disease (OR: 4.8, 95% CI 1.8 to 13), asthma or recurrent wheezing (OR: 2.5, 95% CI 1.2 to 5.2) and after excluding MIS-C patients, moderate/severe liver disease (OR: 8.6, 95% CI 1.6 to 47.6). However, asthmatic children were admitted into the PICU due to MIS-C or pneumonia, not due to asthma flare.Conclusion: Hospitalised children with COVID-19 usually present as one of five major clinical phenotypes of decreasing severity. Risk factors for PICU include MIS-C, elevation of inflammation biomarkers, asthma, moderate or severe liver disease and cardiac disease. What is Known: • All studies suggest that children are less susceptible to serious SARS-CoV-2 infection when compared to adults. Most studies describe symptoms at presentation. However, it remains unclear how these symptoms group together into clinically identifiable syndromes and the severity associated with them. What is New: • We have gathered the primary diagnoses into five major syndromes of decreasing severity: MIS-C, bronchopulmonary syndrome, gastrointestinal syndrome, fever without a source and mild syndrome. Classification of the children in one of the syndromes is unique and helps to assess the risk of critical illness and to define the spectrum of the disease instead of just describing symptoms and signs
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