665 research outputs found

    Propuesta de innovación para la enseñanza de la Física y la Química: Energías renovables

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    En el presente trabajo Fin de Máster se ha elaborado una propuesta didáctica centrada en la temática de las energías renovables, el ahorro energético y la sostenibilidad, destinada a diferentes cursos de Educación Secundaria Obligatoria y Bachillerato. Como estrategias metodológicas y recursos se combina la indagación guiada con la experimentación y el empleo de las TIC, mediante el uso de juegos educativos on-line y aplicaciones Android, y la realización, por parte de los alumnos, de actividades prácticas, basados en pequeñas investigaciones sobre proyectos de sostenibilidad. De este modo, se busca captar el interés de los estudiantes al llevar a la práctica lo aprendido en el aula, y relacionarlo con el conocimiento de su entorno y con la vida cotidiana. Asimismo, se les instruirá sobre el aprovechamiento de algunas energías renovables (solar, eólica e hidroeléctrica) a través de diversas actividades experimentales.Departamento de Didáctica de las Ciencias Sociales y ExperimentalesMáster en Profesor de Educación Secundaria Obligatoria y Bachillerato, Formación Profesional y Enseñanzas de Idioma

    La reversión de la contratación pública en España: y el caso 010 del Ayuntamiento de Zaragoza.

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    Este trabajo de fin de grado aborda un asunto de reversión de los servicios públicos en España: el del caso de la información telefónica del Ayuntamiento de Zaragoza, o más coloquialmente conocido como el caso del 010 del Ayuntamiento de Zaragoza. Con él explicamos cuáles son los factores por los cuales se vuelve a la gestión directa de los servicios públicos, así como también cuáles son los problemas laborales que se producen al revertirse el servicio a la Administración Pública. Principalmente analizamos los tipos de subrogación del personal y su situación laboral tras la reversión. Para poder entender mejor este fenómeno y verlo más en la práctica nos servimos del caso 010 del Ayuntamiento de Zaragoza. Examinaremos también otros conceptos que están relacionados con la contratación pública en España como son la importancia de incluir cláusulas sociales en los procesos de contratación pública y el derecho de la buena administración en relación a la prestación de los servicios públicos a los ciudadanos.<br /

    Murine Anti-vaccinia Virus D8 Antibodies Target Different Epitopes and Differ in Their Ability to Block D8 Binding to CS-E

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    The IMV envelope protein D8 is an adhesion molecule and a major immunodominant antigen of vaccinia virus (VACV). Here we identified the optimal D8 ligand to be chondroitin sulfate E (CS-E). CS-E is characterized by a disaccharide moiety with two sulfated hydroxyl groups at positions 4′ and 6′ of GalNAc. To study the role of antibodies in preventing D8 adhesion to CS-E, we have used a panel of murine monoclonal antibodies, and tested their ability to compete with CS-E for D8 binding. Among four antibody specificity groups, MAbs of one group (group IV) fully abrogated CS-E binding, while MAbs of a second group (group III) displayed widely varying levels of CS-E blocking. Using EM, we identified the binding site for each antibody specificity group on D8. Recombinant D8 forms a hexameric arrangement, mediated by self-association of a small C-terminal domain of D8. We propose a model in which D8 oligomerization on the IMV would allow VACV to adhere to heterogeneous population of CS, including CS-C and potentially CS-A, while overall increasing binding efficiency to CS-E

    Corrigendum: MEF2 transcription factors are key regulators of sprouting angiogenesis

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    The above-mentioned article contained three errors in the Supplemental Figures. In Supplemental Figure 3D, both bar graphs are missing labels for the X-axes due to an oversight during figure preparation

    Guia per gestionar correctament els aliments en centres educatius i altres menjadors socials per a persones amb al·lèrgies, intoleràncies alimentàries i/o malaltia celíaca

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    Al·lèrgies alimentàries; Intoleràncies alimentàries; Malaltia celíaca; Menjadors socialsAlergias alimentarias; Intolerancias alimentarias; Enfermedad celíaca; Comedores socialesFood allergies; Food intolerances; Celiac DiseaseAquesta guia ha estat elaborada per una comunitat de pràctica (CoP) amb l’objectiu de facilitar la gestió dels aliments en menjadors socials. També pretén aclarir conceptes perquè qui hagi de tractar persones amb al·lèrgies o intoleràncies alimentàries i malaltia celíaca tingui la seguretat que actua de la manera correcta en cada moment. En l’elaboració de la guia hi han participat professionals de diversos perfils, que han posat tot el seu coneixement i experiència perquè aquest document sigui útil, entenedor, complet i pràctic. Pel volum d’informació i l’evolució mèdica constant en la definició de conceptes, hem optat per situar en annexos una sèrie de materials perquè els conceptes bàsics siguin més fàcils de localitzar i d’assimilar i la informació més tècnica quedi reservada a les persones que vulguin aprofundir en la matèria. També hem dissenyat tres tallers per practicar alguns conceptes de manera que l’aplicació de la teoria sigui més senzilla. Estan inclosos com a annexos: el semàfor del risc, l’elaboració de fitxes tècniques i l’anafilaxi i com actuar davant d’una reacció adversa greu.Esta guía ha sido elaborada por una comunidad de práctica (CoP) con el objetivo de facilitar la gestión de los alimentos en comedores sociales. También pretende aclarar conceptos para que quien tenga que tratar a personas con alergias o intolerancias alimentarias y enfermedad celíaca tenga la seguridad de que actúa de la manera correcta en cada momento. En la elaboración de la guía han participado profesionales de diversos perfiles, que han puesto todo su conocimiento y experiencia para que este documento sea útil, comprensible, completo y práctico. Por el volumen de información y la evolución médica constante en la definición de conceptos, hemos optado por situar en anexos una serie de materiales para que los conceptos básicos sean más fáciles de localizar y asimilar y la información más técnica quede reservada a las personas que quieran profundizar en la materia. También hemos diseñado tres talleres para practicar algunos conceptos de forma que la aplicación de la teoría sea más sencilla. Están incluidos como anexos: el semáforo del riesgo, la elaboración de fichas técnicas y el anafilaxis y cómo actuar ante una reacción adversa grave.This guide has been prepared by a community of practice (CoP) with the aim of facilitating food management in soup kitchens. It also aims to clarify concepts so that anyone who has to treat people with food allergies or intolerances and celiac disease can be sure that they are acting in the correct way at all times. Professionals with various profiles have participated in the preparation of the guide, who have put all their knowledge and experience to make this document useful, understandable, complete and practical. Due to the volume of information and the constant medical evolution in the definition of concepts, we have chosen to place a series of materials in annexes so that the basic concepts are easier to locate and assimilate and the more technical information is reserved for people who want to. go deeper into the matter. We have also designed three workshops to practice some concepts so that the application of the theory is easier. Included as annexes are: the risk traffic light, the preparation of technical sheets and anaphylaxis and how to act in the event of a serious adverse reaction

    Structure-Guided Redesign Improves NFL HIV Env Trimer Integrity and Identifies an Inter-Protomer Disulfide Permitting Post-Expression Cleavage

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    Soluble HIV-1 envelope glycoprotein (Env) trimers are under active investigation as vaccine candidates in relevant pre-clinical models. Like SOSIPs, the cleavage-independent native flexibly linked (NFL) trimers are faithful mimics of the Env spike. Here, we analyzed multiple new designs to explore alternative modifications, informing tertiary interactions, while maintaining NFL trimer homogeneity and integrity. Accordingly, we performed a proline (P) substitution screen in the gp41 heptad repeat 1 region, identifying other trimer-enhancing Ps, including L555P. This P improved trimer integrity compared to I559P in selected properties. Next, we screened 15 structure-guided potential cysteine pairs in gp140 and found that A501C-L663C (“CC2”) forms an inter-protomer disulfide bond that demonstrably increased NFL trimer thermostability. We combined these two approaches with trimer-derived substitutions, coupled with glycine substitutions at helix-to-coil transitions, developed by our group. To increase the exposure of the fusion peptide (FP) N-terminus, we engineered an enterokinase (EK) cleavage site upstream of the FP for controlled post-expression cleavage. In combination, the redesigns resulted in highly stable and homogeneous NFL mimics derived from different clades. Following recombinant EK cleavage, the NFL trimers retained covalent linkage, maintaining a native-like structure while displaying enhanced stability and favorable antigenic features. These trimers also displayed increased exposure of neutralizing epitopes in the FP and gp120/gp41 interface, while retaining other neutralizing epitopes and occluding non-neutralizing elements. This array of Env-structure-guided designs reveals additional interactive regions in the prefusion state of the HIV Env spike, affording the development of novel antigens and immunogens

    Relevance of gastrointestinal manifestations in a large Spanish cohort of patients with systemic lupus erythematosus: what do we know?

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    SLE can affect any part of the gastrointestinal (GI) tract. GI symptoms are reported to occur in >50% of SLE patients. To describe the GI manifestations of SLE in the RELESSER (Registry of SLE Patients of the Spanish Society of Rheumatology) cohort and to determine whether these are associated with a more severe disease, damage accrual and a worse prognosis. METHODS: We conducted a nationwide, retrospective, multicentre, cross-sectional cohort study of 3658 SLE patients who fulfil =4 ACR-97 criteria. Data on demographics, disease characteristics, activity (SLEDAI-2K or BILAG), damage (SLICC/ACR/DI) and therapies were collected. Demographic and clinical characteristics were compared between lupus patients with and without GI damage to establish whether GI damage is associated with a more severe disease. RESULTS: From 3654 lupus patients, 3.7% developed GI damage. Patients in this group (group 1) were older, they had longer disease duration, and were more likely to have vasculitis, renal disease and serositis than patients without GI damage (group 2). Hospitalizations and mortality were significantly higher in group 1. Patients in group 1 had higher modified SDI (SLICC Damage Index). The presence of oral ulcers reduced the risk of developing damage in 33% of patients. CONCLUSION: Having GI damage is associated with a worse prognosis. Patients on a high dose of glucocorticoids are at higher risk of developing GI damage which reinforces the strategy of minimizing glucocorticoids. Oral ulcers appear to decrease the risk of GI damage. © The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Rheumatology

    Pharmacological targeting of the transcription factor SOX18 delays breast cancer in mice.

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    Pharmacological targeting of transcription factors holds great promise for the development of new therapeutics, but strategies based on blockade of DNA binding, nuclear shuttling, or individual protein partner recruitment have yielded limited success to date. Transcription factors typically engage in complex interaction networks, likely masking the effects of specifically inhibiting single protein-protein interactions. Here, we used a combination of genomic, proteomic and biophysical methods to discover a suite of protein-protein interactions involving the SOX18 transcription factor, a known regulator of vascular development and disease. We describe a small-molecule that is able to disrupt a discrete subset of SOX18-dependent interactions. This compound selectively suppressed SOX18 transcriptional outputs in vitro and interfered with vascular development in zebrafish larvae. In a mouse pre-clinical model of breast cancer, treatment with this inhibitor significantly improved survival by reducing tumour vascular density and metastatic spread. Our studies validate an interactome-based molecular strategy to interfere with transcription factor activity, for the development of novel disease therapeutics

    Finishing the euchromatic sequence of the human genome

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    The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead
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