Assessment of carbon black modified binder in a sustainable asphalt concrete mixture

Carbon black has been used as a modifier in conventional binders together with a relatively low percentage of SBS polymer. In addition, an Evotherm additive has been combined by the wet way with the aim of decreasing the manufacturing temperature of the asphalt mixtures. The impact of these two has been analysed with a DSR rheometer, showing an increase in stiffness. An Asphalt Concrete mixture was then designed using the experimental binder and the warm mix additive and compared with a reference mix, using a commercial polymer modified bitumen. The final experimental mixture was manufactured 15?°C cooler than usual, showing good mechanical performance despite the low percentage of natural aggregate, which was mostly composed of reclaimed asphalt and slag. Its stiffness and fatigue resistance were also investigated. Finally, the mixture was laid in an experimental road section under real conditions as proof of concept of the technology.The authors would like to acknowledge that the research leading to these results has received funding from the European Union’s Seventh Programme for Research, Technological Development and Demonstration under Grant Agreement nº 605404

La marca país: su origen y evolución, caso Ecuador

In the last decades, countries in their strategies include the country brand as one of their competitive advantages that will help strengthen its international image in order to promote both tourism and exports. Ecuador has looked for the alignment with the global trend consolidating the process of creating and disseminating the brand “Ecuador loves life”; and in that way the imaginary that communicates, and contributes to present to the world a country with cultural and natural richness.Durante las últimas décadas, los países dentro de sus estrategias incluyen la marca país como una de sus ventajas competitivas, que le ayudará a fortalecer su imagen internacional a fin de favorecer tanto el turismo como sus exportaciones. Ecuador ha buscado alinearse con la tendencia mundial y es así como consolida un proceso de creación y difusión de su marca “Ecuador ama la vida”; y de ese modo cuida que el imaginario que comunique, favorezca el presentar al mundo un país con riqueza tanto cultural como natural

Producción de una hormona animal recombinante estable y con actividad in vivo.

Actualmente, en ganadería vacuna intensiva, la fertilización de las vacas se produce por inseminación artificial. Para obtener un mayor rendimiento, se extraen hormonas naturales de determinados animales para inyectarlas al ganado vacuno y conseguir la hiperovulación de éstos, pudiendo inseminar todas al mismo tiempo y con mayor probabilidad de éxito. El problema es que la extracción de estas hormonas es compleja y cara. Se ha intentado solventar este problema produciendo esta hormona en cultivos celulares de mamíferos o insectos mediante ingeniería genética. Aunque las enzimas recombinantes demuestran actividad in vitro, al inyectarlas a modelos animales o ganado no inducen la hiperovulación debido a una vida media en suero mucho más corta (minutos) que la versión natural (horas), ya que son eliminadas de la sangre rápidamente por la orina. Bionaturis ha propuesto la estabilización en suero de esta hormona recombinante mediante la fusión de secuencias estabilizadoras desarrolladas por la empresa a la secuencia hormonal.Bionaturis utiliza la plataforma FLYLIFE, que consiste en el uso del sistema baculovírico para la producción de proteínas recombinantes. A partir de secuencias estabilizadoras ya sintetizadas, se creó un vector de transferencia con las secuencias de interés mediante técnicas de clonación. Luego, mediante recombinación homóloga, se insertarán estas secuencias en baculovirus modificados genéticamente (Master Viral DNA de Bionaturis) que, en vez de sintetizar polihedrina, sintetizan la secuencia de interés, y así obtener baculovirus recombinantes de trabajo (Working Viral Banks). La obtención de los Working Virus Bank (WBK) se realiza mediante la co-transfección en células de insecto con el Master Viral DNA y el vector de transferencia. Hasta ahora, se ha llevado a cabo la construcción del vector de transferencia con éxito, los siguientes pasos a dar son la co-transfección para la obtención del WVB y su posterior caracterización mediante test de expresión de proteínas en cultivo celular. Posteriormente, se pretende la infección de larvas de lepidóptero con el virus recombinante obtenido que, al multiplicarse en su interior, producirá la proteína recombinante. Finalmente, se extraerá y se purificará la proteína de interés y se evaluará su actividad in vitro e in vivo

Intervención educativa: Capacitación de estudiantes de la Facultad de Enfermería, Fisioterapia y Podología en la elaboración de un trabajo fin de grado mediante cuestionarios de autoaprendizaje

Se crea una herramienta en el Campus Virtual (CV), en formato de Libro de Moodle, que permita la orientación del estudiante en el proceso de elaboración del Trabajo Fin de Grado (TFG), mediante el procedimiento de Preguntas Frecuentes que vayan contestando a las principales inquietudes y carencias del estudiante al enfrentarse a dicha tarea. Asimismo se diseña un cuestionario de Autoevaluación de conocimientos y habilidades que permita al estudiante apreciar su progreso en el manejo de los conceptos relacionados con su trabajo. Por último se pretende identificar el nivel de conocimientos y habilidades adquirido por los estudiantes, de forma que podamos evaluar la eficacia de nuestra intervención educativa. Este objetivo lo abordaremos con procedimientos de cuantitativos y cualitativos

Transcription factor NRF2 uses the Hippo pathway effector TAZ to induce tumorigenesis in glioblastomas

Transcription factor NRF2 orchestrates a cellular defense against oxidative stress and, so far, has been involved in tumor progression by providing a metabolic adaptation to tumorigenic demands and resistance to chemotherapeutics. In this study, we discover that NRF2 also propels tumorigenesis in gliomas and glioblastomas by inducing the expression of the transcriptional co-activator TAZ, a protein of the Hippo signaling pathway that promotes tumor growth. The expression of the genes encoding NRF2 (NFE2L2) and TAZ (WWTR1) showed a positive correlation in 721 gliomas from The Cancer Genome Atlas database. Moreover, NRF2 and TAZ protein levels also correlated in immunohistochemical tissue arrays of glioblastomas. Genetic knock-down of NRF2 decreased, while NRF2 overexpression or chemical activation with sulforaphane, increased TAZ transcript and protein levels. Mechanistically, we identified several NRF2-regulated functional enhancers in the regulatory region of WWTR1. The relevance of the new NRF2/TAZ axis in tumorigenesis was demonstrated in subcutaneous and intracranial grafts. Thus, intracranial inoculation of NRF2-depleted glioma stem cells did not develop tumors as determined by magnetic resonance imaging. Forced TAZ overexpression partly rescued both stem cell growth in neurospheres and tumorigenicity. Hence, NRF2 not only enables tumor cells to be competent to proliferate but it also propels tumorigenesis by activating the TAZ-mediated Hippo transcriptional program.This study was funded by the Spanish Ministry of Economy and Competitiveness (MINECO) under the grant SAF2016-76520-R. ME is recipient of a postdoctoral contract Juan de la Cierva; DL and NRA of a FPU contract of MINECO; MP and RFG of a FPI contracts of Autonomous University of Madrid. RG has been funded by the AECC Scientific Foundation

The level of caveolin-1 expression determines response to TGF-ß as a tumor suppressor in hepatocellular carcinoma cells

Hepatocellular carcinoma (HCC) is a heterogeneous tumour associated with poor prognostic outcome. Caveolin-1 (CAV1), a membrane protein involved in the formation of caveolae, is frequently overexpressed in HCC. Transforming growth factor-beta (TGF-β) is a pleiotropic cytokine having a dual role in hepatocarcinogenesis: inducer of apoptosis at early phases, but pro-tumourigenic once cells acquire mechanisms to overcome its suppressor effects. Apoptosis induced by TGF-β is mediated by upregulation of the NADPH oxidase NOX4, but counteracted by transactivation of the epidermal growth factor receptor (EGFR) pathway. Previous data suggested that CAV1 is required for the anti-apoptotic signals triggered by TGF-β in hepatocytes. Whether this mechanism is relevant in hepatocarcinogenesis has not been explored yet. Here we analysed the TGF-β response in HCC cell lines that express different levels of CAV1. Accordingly, stable CAV1 knockdown or overexpressing cell lines were generated. We demonstrate that CAV1 is protecting HCC cells from TGF-β-induced apoptosis, which attenuates its suppressive effect on clonogenic growth and increases its effects on cell migration. Downregulation of CAV1 in HLE cells promotes TGF-β-mediated induction of the pro-apoptotic BMF, which correlates with upregulation of NOX4, whereas CAV1 overexpression in Huh7 cells shows the opposite effect. CAV1 silenced HLE cells show attenuation in TGF-β-induced EGFR transactivation and activation of the PI3K/AKT pathway. On the contrary, Huh7 cells, which do not respond to TGF-β activating the EGFR pathway, acquire the capacity to do so when CAV1 is overexpressed. Analyses in samples from HCC patients revealed that tumour tissues presented higher expression levels of CAV1 compared with surrounding non-tumoural areas. Furthermore, a significant positive correlation among the expression of CAV1 and TGFB1 was observed. We conclude that CAV1 has an essential role in switching the response to TGF-β from cytostatic to tumourigenic, which could have clinical meaning in patient stratification

Hereditary Leiomyomatosis and Renal Cell Cancer Syndrome in Spain: Clinical and Genetic Characterization

Simple Summary Hereditary leiomyomatosis and renal cell cancer (HLRCC) syndrome is a very rare hereditary disorder characterized by cutaneous leiomyomas (CLMs), uterine leiomyomas (ULMs), renal cysts (RCys) and renal cell cancer (RCC), with no data on its prevalence worldwide. No genotype-phenotype associations have been described. The aim of our study was to describe the genotypic and phenotypic features of the largest series of patients with HLRCC from Spain reported to date. Of 27 FH germline pathogenic variants, 12 were not previously reported in databases. Patients with missense pathogenic variants showed higher frequencies of CLMs, ULMs and RCys, than those with loss-of-function variants. The frequency of RCCs (10.9%) was lower than those reported in the previously published series. Hereditary leiomyomatosis and renal cell cancer syndrome (HLRCC) is a very rare hereditary disorder characterized by cutaneous leiomyomas (CLMs), uterine leiomyomas (ULMs), renal cysts (RCys) and renal cell cancers (RCCs). We aimed to describe the genetics, clinical features and potential genotype-phenotype associations in the largest cohort of fumarate hydratase enzyme mutation carriers known from Spain using a multicentre, retrospective study of individuals with a genetic or clinical diagnosis of HLRCC. We collected clinical information from medical records, analysed genetic variants and looked for genotype-phenotype associations. Analyses were performed using R 3.6.0. software. We included 197 individuals: 74 index cases and 123 relatives. CLMs were diagnosed in 65% of patients, ULMs in 90% of women, RCys in 37% and RCC in 10.9%. Twenty-seven different pathogenic variants were detected, 12 (44%) of them not reported previously. Patients with missense pathogenic variants showed higher frequencies of CLMs, ULMs and RCys, than those with loss-of-function variants (p = 0.0380, p = 0.0015 and p = 0.024, respectively). This is the first report of patients with HLRCC from Spain. The frequency of RCCs was lower than those reported in the previously published series. Individuals with missense pathogenic variants had higher frequencies of CLMs, ULMs and RCys

Trends in detection of invasive cancer and ductal carcinoma in situ at biennial screening mammography in spain : A retrospective cohort study

Background: Breast cancer incidence has decreased in the last decade, while the incidence of ductal carcinoma in situ (DCIS) has increased substantially in the western world. The phenomenon has been attributed to the widespread adaption of screening mammography. The aim of the study was to evaluate the temporal trends in the rates of screen detected invasive cancers and DCIS, and to compare the observed trends with respect to hormone replacement therapy (HRT) use along the same study period. Methods: Retrospective cohort study of 1,564,080 women aged 45-69 years who underwent 4,705,681 screening mammograms from 1992 to 2006. Age-adjusted rates of screen detected invasive cancer, DCIS, and HRT use were calculated for first and subsequent screenings. Poisson regression was used to evaluate the existence of a change-point in trend, and to estimate the adjusted trends in screen detected invasive breast cancer and DCIS over the study period. Results: The rates of screen detected invasive cancer per 100.000 screened women were 394.0 at first screening, and 229.9 at subsequent screen. The rates of screen detected DCIS per 100.000 screened women were 66.8 at first screen and 43.9 at subsequent screens. No evidence of a change point in trend in the rates of DCIS and invasive cancers over the study period were found. Screen detected DCIS increased at a steady 2.5% per year (95% CI: 1.3; 3.8), while invasive cancers were stable. Conclusion: Despite the observed decrease in breast cancer incidence in the population, the rates of screen detected invasive cancer remained stable during the study period. The proportion of DCIS among screen detected breast malignancies increased from 13% to 17% throughout the study period. The rates of screen detected invasive cancer and DCIS were independent of the decreasing trend in HRT use observed among screened women after 2002

Blood RNA sequencing reveals immunological processes associated with the response to abatacept in rheumatoid arthritis.

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