93 research outputs found

    Tumor and circulating biomarkers in patients with second-line hepatocellular carcinoma from the randomized phase II study with tivantinib

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    ARQ 197-215 was a randomized placebo-controlled phase II study testing the MET inhibitor tivantinib in second-line hepatocellular carcinoma (HCC) patients. It identified tumor MET as a key biomarker in HCC. Aim of this research was to study the prognostic and predictive value of tumor (MET, the receptor tyrosine kinase encoded by the homonymous MNNG-HOS transforming gene) and circulating (MET, hepatocyte growth factor [HGF], alpha-fetoprotein [AFP], vascular endothelial growth factor [VEGF]) biomarkers in second-line HCC. Tumor MET-High status was centrally assessed by immunohistochemistry. Circulating biomarkers were centrally analyzed on serum samples collected at baseline and every 4-8 weeks, using medians as cut-off to determine High/Low status. Tumor MET, tested in 77 patients, was more frequently High after (82%) versus before (40%) sorafenib. A significant interaction (p = 0.04) between tivantinib and baseline tumor MET in terms of survival was observed. Baseline circulating MET and HGF (102 patients) High status correlated with shorter survival (HR 0.61, p = 0.03, and HR 0.60, p = 0.02, respectively), while the association between AFP (104 patients) or VEGF (103 patients) status and survival was non-significant. Conclusions: Tumor MET levels were higher in patients treated with sorafenib. Circulating biomarkers such as MET and HGF may be prognostic in second-line HCC. These results need to be confirmed in larger randomized clinical trials

    Investigation into the role of carboxylic acid and phenolic hydroxyl groups in the plant biostimulant activity of a humic acid purified from an oxidized sub-bituminous coal

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    IntroductionHumic substances (HS) are increasingly being applied as crop plant biostimulants because they have been shown to increase plant productivity, especially under environmentally stressful conditions. There has been intense interest in elucidating the HS molecular structures responsible for eliciting the plant biostimulant response (PBR). The polar and weakly acidic carboxylic (COOH) and phenolic hydroxyl (ArOH) functional groups play major roles in the acid nature, pH dependent solubilities, conformation, and metal- and salt-binding capabilities of HS. Reports on the role played by these groups in the PBR of HS found growth parameters being both positively and negatively correlated with COOH and ArOH functionalities.Materials and methodsTo investigate the role of COOH and ArOH in HS biostimulant activity we used a humic acid (HA), purified from an oxidized sub bituminous coal to prepare HAs with COOH groups methylated (AHA), ArOH groups acetylated (OHA), and with both COOH and ArOH groups methylated (FHA). The original HA was designated (NHA). The four HAs were subjected to elemental, 13C-NMR, FTIR, and EPR analyses and their antioxidant properties were assessed using the trolox equivalents antioxidant capacity assay (TEAC). 13C-NMR and FTIR analysis revealed significant alkylation/acetylation. To determine the effects of alkylating/acetylating these functional groups on the HA elicited PBR, the HAs were evaluated in a plant bioassay on corn (Zea mays L.) seedling under nutrient and non-nutrient stressed conditions. Treatments consisted of the four HAs applied to the soil surface at a concentration of 80 mg C L−1, in 50 ml DI H2O with the control plants receiving 50ml DI H2O.ResultsThe HA-treated plants, at both fertilization rates, were almost always significantly larger than their respective control plants. However, the differences produced under nutrient stress were always much greater than those produced under nutrient sufficiency, supporting previous reports that HA can reduce the effects of stress on plant growth. In addition, for the most part, the HAs with the alkylated/acetylated groups produced plants equal to or larger than plants treated with NHA.ConclusionThese results suggests that COOH and ArOH groups play a limited or no role in the HA elicited PBR. Alternatively, the HA pro-oxidant to antioxidant ratio may play a role in the magnitude of the biostimulant response

    Propuesta Estratégica de Mejora en la Implementación de los Estándares Mínimos del Sistema de Gestión de la Seguridad y Salud en el Trabajo, en la Empresa Costured Ltda, para el Primer Semestre de 2019

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    En el siguiente trabajo colaborativo quedará plasmado todo lo referente al diplomado de profundización en gerencia de talento humano Con el fin de abreviar las unidades vistas, de la misma forma continuar con el trabajo investigativo en la empresa Costured Ltda, el cual ha dado resultados significativos para la mejora de la organización, resaltando así la importancia de la gerencia de talento humano al integrar los diferentes conceptos y temáticas relacionados para la elaboración de estrategias que permitan potenciar la organización a través del desarrollo y retención del talento humano que la componen y así mismo tomar medidas y decisiones estratégicas acordes con las necesidades de la organización, las cuales buscan contribuir a la consecución de los objetivos organizacionales. Por otra parte este documento aplica las temáticas con base en las herramientas tecnológicas y teóricas dispuestas en los diferentes entornos del curso, lo cual nos permite dar conceptos más claros, consultados en fuentes confiables de información, que finalmente nos permite dar recomendaciones claras y concisas resaltando la importancia de diseñar y ejecutar planes y programas relacionados con el SG-SST siendo este el desarrollo de un proceso lógico y por etapas basado en la mejora continua, lo cual incluye la política, la organización, la planificación, la aplicación, la evaluación ,la auditoría y las acciones de mejora con el objetivo de anticipar, reconocer, evaluar y controlar los riesgos que puedan afectar la seguridad y la salud en los espacios laborales.In the following collaborative work will be reflected everything related to the deepening diploma in human talent management In order to abbreviate the units seen, in the same way continue with the investigative work in the company Costured Ltda, which has given significant results for the improvement of the organization, highlighting the importance of human talent management by integrating the different concepts and related topics for the development of strategies that allow the organization to be strengthened through the development and retention of the human talent that compose it and also take measures and strategic decisions in accordance with the needs of the organization, which seek to contribute to the achievement of organizational objectives. On the other hand this document applies the themes based on the technological and theoretical tools available in the different environments of the course, which allows us to give clearer concepts, consulted in reliable sources of information, which finally allows us to give clear and concise recommendations highlighting the importance of designing and executing plans and programs related to the SG-SST, this being the development of a logical and stepwise process based on continuous improvement, which includes policy, organization, planning, application, evaluation, the audit and improvement actions with the aim of anticipating, recognizing, evaluating and controlling risks that may affect safety and health in work spaces

    Response inhibition and serotonin in autism:a functional MRI study using acute tryptophan depletion

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    It has been suggested that the restricted, stereotyped and repetitive behaviours typically found in autism are underpinned by deficits of inhibitory control. The biological basis of this is unknown but may include differences in the modulatory role of neurotransmitters, such as serotonin, which are implicated in the condition. However, this has never been tested directly. We therefore assessed the modifying role of serotonin on inhibitory brain function during a Go/No-Go task in 14 adults with autism and normal intelligence and 14 control subjects that did not differ in gender, age and intelligence. We undertook a double-blind, placebo-controlled, crossover trial of acute tryptophan depletion using functional magnetic resonance imaging. Following sham, adults with autism relative to controls had reduced activation in key inhibitory regions of inferior frontal cortex and thalamus, but increased activation of caudate and cerebellum. However, brain activation was modulated in opposite ways by depletion in each group. Within autistic individuals depletion upregulated fronto-thalamic activations and downregulated striato-cerebellar activations toward control sham levels, completely 'normalizing' the fronto-cerebellar dysfunctions. The opposite pattern occurred in controls. Moreover, the severity of autism was related to the degree of differential modulation by depletion within frontal, striatal and thalamic regions. Our findings demonstrate that individuals with autism have abnormal inhibitory networks, and that serotonin has a differential, opposite, effect on them in adults with and without autism. Together these factors may partially explain the severity of autistic behaviours and/or provide a novel (tractable) treatment target

    Image-guided Placement of Magnetic Neuroparticles as a Potential High-Resolution Brain-Machine Interface

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    We are developing methods of noninvasively delivering magnetic neuroparticlesâ„¢ via intranasal administration followed by image-guided magnetic propulsion to selected locations in the brain. Once placed, the particles can activate neurons via vibrational motion or magnetoelectric stimulation. Similar particles might be used to read out neuronal electrical pulses via spintronic or liquid-crystal magnetic interactions, for fast bidirectional brain-machine interface. We have shown that particles containing liquid crystals can be read out with magnetic resonance imaging (MRI) using embedded magnetic nanoparticles and that the signal is visible even for voltages comparable to physiological characteristics. Such particles can be moved within the brain (e.g., across midline) without causing changes to neurological firing

    RV Kronprins Håkon (cruise no. 2019708) Longyearbyen – Longyearbyen 19.09. – 16.10.2019

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    The HACON cruise is a major component of the FRINATEK HACON project, which aims at investigating the role of the Gakkel Ridge and Arctic Ocean in biological connectivity amongst ocean basins and global biogeography of chemosynthetic ecosystems. The HACON study area is centered in the Aurora seamount and Aurora vent field

    Evasion of anti-growth signaling: a key step in tumorigenesis and potential target for treatment and prophylaxis by natural compounds

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    The evasion of anti-growth signaling is an important characteristic of cancer cells. In order to continue to proliferate, cancer cells must somehow uncouple themselves from the many signals that exist to slow down cell growth. Here, we define the anti-growth signaling process, and review several important pathways involved in growth signaling: p53, phosphatase and tensin homolog (PTEN), retinoblastoma protein (Rb), Hippo, growth differentiation factor 15 (GDF15), AT-rich interactive domain 1A (ARID1A), Notch, insulin-like growth factor (IGF), and Krüppel-like factor 5 (KLF5) pathways. Aberrations in these processes in cancer cells involve mutations and thus the suppression of genes that prevent growth, as well as mutation and activation of genes involved in driving cell growth. Using these pathways as examples, we prioritize molecular targets that might be leveraged to promote anti-growth signaling in cancer cells. Interestingly, naturally-occurring phytochemicals found in human diets (either singly or as mixtures) may promote anti-growth signaling, and do so without the potentially adverse effects associated with synthetic chemicals. We review examples of naturally-occurring phytochemicals that may be applied to prevent cancer by antagonizing growth signaling, and propose one phytochemical for each pathway. These are: epigallocatechin-3-gallate (EGCG) for the Rb pathway, luteolin for p53, curcumin for PTEN, porphyrins for Hippo, genistein for GDF15, resveratrol for ARID1A, withaferin A for Notch and diguelin for the IGF1-receptor pathway. The coordination of anti-growth signaling and natural compound studies will provide insight into the future application of these compounds in the clinical setting

    ERG finally has something to YAP about in prostate cancer

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    SummaryThe significance of ERG in human prostate cancer is unclear because mouse prostate is resistant to ERG-mediated transformation. We determined that ERG activates the transcriptional program regulated by YAP1 of the Hippo signaling pathway and found that prostate-specific activation of either ERG or YAP1 in mice induces similar transcriptional changes and results in age-related prostate tumors. ERG binds to chromatin regions occupied by TEAD/YAP1 and transactivates Hippo target genes. In addition, in human luminal-type prostate cancer cells, ERG binds to the promoter of YAP1 and is necessary for YAP1 expression. These results provide direct genetic evidence of a causal role for ERG in prostate cancer and reveal a connection between ERG and the Hippo signaling pathway

    Implementation of virtual learning environments as a motivating strategy for the development of reading skills

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    El presente artículo presenta los resultados derivados del estudio Implementación de Ambientes virtuales de Aprendizaje como estrategia motivadora para el desarrollo de competencias lectoras. Además de analizar el uso de ambientes virtuales de aprendizaje como estrategia motivadora para el desarrollo de competencias lectoras, se proponen alternativas pertinentes para dinamizar los espacios de enseñanza-aprendizaje. La problemática general en las aulas de clases en torno al proceso de aprendizaje y en específico de las competencias lectoras de los estudiantes, promueve la búsqueda de caminos para el aprovechamiento y la estructuración de oportunidades para que el colectivo de docentes fortalezcna e innoven en sus prácticas pedagógicas y así generar mayor interés y motivación en ellos. La población objeto de estudio estuvo conformada por estudiantes de 9 grado de la Institución Educativa Néstor Andrés Rangel Alfaro. El estudio tuvo como propósito fomentar los ambientes virtuales de aprendizaje como una estrategia motivadora que fortalece el del desarrollo de las competencias lectorasThis article presents the results derived from the study Implementation of virtual learning environments as a motivating strategy for the development of reading skills; In addition to establishing how the use of virtual learning environments as a motivating strategy for the development of reading skills, it is relevant to boost the teaching-learning spaces. The general problems in the classroom around the learning process and specifically the reading skills of students, promotes the structuring of opportunities for teachers to strengthen and innovate in their pedagogical practices and thus generate greater interest and motivation in them. The population studied was made up of 9th grade students from the Néstor Andrés Rangel Alfaro Educational Institution. The purpose of the study was to promote virtual learning environments as a motivating strategy that strengthens the development of reading skills
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