8 resultados para EFFECTIVE WORK FUNCTION
em Archivo Digital para la Docencia y la Investigación - Repositorio Institucional de la Universidad del País Vasco
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In the framework of dielectric theory, the static non-local self-energy of an electron near an ultra-thin polarizable layer has been calculated and applied to study binding energies of image-potential states near free-standing graphene. The corresponding series of eigenvalues and eigenfunctions have been obtained by numerically solving the one-dimensional Schrodinger equation. The imagepotential state wave functions accumulate most of their probability outside the slab. We find that the random phase approximation (RPA) for the nonlocal dielectric function yields a superior description for the potential inside the slab, but a simple Fermi-Thomas theory can be used to get a reasonable quasi-analytical approximation to the full RPA result that can be computed very economically. Binding energies of the image-potential states follow a pattern close to the Rydberg series for a perfect metal with the addition of intermediate states due to the added symmetry of the potential. The formalism only requires a minimal set of free parameters: the slab width and the electronic density. The theoretical calculations are compared with experimental results for the work function and image-potential states obtained by two-photon photoemission.
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[ES]La fibrilación ventricular (VF) es el primer ritmo registrado en el 40\,\% de las muertes súbitas por paro cardiorrespiratorio extrahospitalario (PCRE). El único tratamiento eficaz para la FV es la desfibrilación mediante una descarga eléctrica. Fuera del hospital, la descarga se administra mediante un desfibrilador externo automático (DEA), que previamente analiza el electrocardiograma (ECG) del paciente y comprueba si presenta un ritmo desfibrilable. La supervivencia en un caso de PCRE depende fundamentalmente de dos factores: la desfibrilación temprana y la resucitación cardiopulmonar (RCP) temprana, que prolonga la FV y por lo tanto la oportunidad de desfibrilación. Para un correcto análisis del ritmo cardiaco es necesario interrumpir la RCP, ya que, debido a las compresiones torácicas, la RCP introduce artefactos en el ECG. Desafortunadamente, la interrupción de la RCP afecta negativamente al éxito en la desfibrilación. En 2003 se aprobó el uso del DEA en pacientes entre 1 y 8 años. Los DEA, que originalmente se diseñaron para pacientes adultos, deben discriminar de forma precisa las arritmias pediátricas para que su uso en niños sea seguro. Varios DEAs se han adaptado para uso pediátrico, bien demostrando la precisión de los algoritmos para adultos con arritmias pediátricas, o bien mediante algoritmos específicos para arritmias pediátricas. Esta tesis presenta un nuevo algoritmo DEA diseñado conjuntamente para pacientes adultos y pediátricos. El algoritmo se ha probado exhaustivamente en bases de datos acordes a los requisitos de la American Heart Association (AHA), y en registros de resucitación con y sin artefacto RCP. El trabajo comenzó con una larga fase experimental en la que se recopilaron y clasificaron retrospectivamente un total de 1090 ritmos pediátricos. Además, se revisó una base de arritmias de adultos y se añadieron 928 nuevos ritmos de adultos. La base de datos final contiene 2782 registros, 1270 se usaron para diseñar el algoritmo y 1512 para validarlo. A continuación, se diseñó un nuevo algoritmo DEA compuesto de cuatro subalgoritmos. Estos subalgoritmos están basados en un conjunto de nuevos parámetros para la detección de arritmias, calculados en diversos dominios de la señal, como el tiempo, la frecuencia, la pendiente o la función de autocorrelación. El algoritmo cumple las exigencias de la AHA para la detección de ritmos desfibrilables y no-desfibrilables tanto en pacientes adultos como en pediátricos. El trabajo concluyó con el análisis del comportamiento del algoritmo con episodios reales de resucitación. En los ritmos que no contenían artefacto RCP se cumplieron las exigencias de la AHA. Posteriormente, se estudió la precisión del algoritmo durante las compresiones torácicas, antes y después de filtrar el artefacto RCP. Para suprimir el artefacto se utilizó un nuevo método desarrollado a lo largo de la tesis. Los ritmos desfibrilables se detectaron de forma precisa tras el filtrado, los no-desfibrilables sin embargo no.
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14 p.
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353 págs.
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En español:El sector público gestiona una gran cantidad de recursos para satisfacer las demandas de la sociedad de bienes y servicios públicos, como sanidad, educación, prestaciones sociales, etc. Y, cada vez más, se reclama por parte de los ciudadanos una utilización eficaz, y eficiente de dichos recursos. Es por ello que el papel de las instituciones que realizan el control del gasto público adquiere una importancia relevante. Este trabajo tiene como objetivo analizar cómo se lleva a cabo el control del gasto público en España, analizando los diferentes niveles de control, así como las instituciones que lo realizan y las relaciones existentes entre ellas, pudiendo constatar la necesidad de coordinación entre ellas para que los recursos que se destinan a la función de control no sean utilizados ineficientemente.
Current Approaches for Predicting a Lack of Response to Anti-EGFR Therapy in KRAS Wild-Type Patients
Resumo:
Targeting epidermal growth factor receptor (EGFR) has been one of the most effective colorectal cancer strategies. Anti-EGFR antibodies function by binding to the extracellular domain of EGFR, preventing its activation, and ultimately providing clinical benefit. KRAS mutations in codons 12 and 13 are recognized prognostic and predictive biomarkers that should be analyzed at the clinic prior to the administration of anti-EGFR therapy. However, still an important fraction of KRAS wild-type patients do not respond to the treatment. The identification of additional genetic determinants of primary or secondary resistance to EGFR targeted therapy for further improving the selection of patients is urgent. Herein, we review the latest published literature highlighting the most important genes that may predict resistance to anti-EGFR monoclonal antibodies in colorectal cancer patients. According to the available findings, the evaluation of BRAF, NRAS, PIK3CA, and PTEN status could be the right strategy to select patients who are likely to respond to anti-EGFR therapies. In the future, the combination of those biomarkers will help establish consensus that can be introduced into clinical practice.
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Elucidating the intricate relationship between brain structure and function, both in healthy and pathological conditions, is a key challenge for modern neuroscience. Recent progress in neuroimaging has helped advance our understanding of this important issue, with diffusion images providing information about structural connectivity (SC) and functional magnetic resonance imaging shedding light on resting state functional connectivity (rsFC). Here, we adopt a systems approach, relying on modular hierarchical clustering, to study together SC and rsFC datasets gathered independently from healthy human subjects. Our novel approach allows us to find a common skeleton shared by structure and function from which a new, optimal, brain partition can be extracted. We describe the emerging common structure-function modules (SFMs) in detail and compare them with commonly employed anatomical or functional parcellations. Our results underline the strong correspondence between brain structure and resting-state dynamics as well as the emerging coherent organization of the human brain.
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Background: In complex with its cofactor UAF1, the USP1 deubiquitinase plays an important role in cellular processes related to cancer, including the response to DNA damage. The USP1/UAF1 complex is emerging as a novel target in cancer therapy, but several aspects of its function and regulation remain to be further clarified. These include the role of the serine 313 phosphorylation site, the relative contribution of different USP1 sequence motifs to UAF1 binding, and the potential effect of cancer-associated mutations on USP1 regulation by autocleavage. Methods: We have generated a large set of USP1 structural variants, including a catalytically inactive form (C90S), non-phosphorylatable (S313A) and phosphomimetic (S313D) mutants, deletion mutants lacking potential UAF1 binding sites, a mutant (GG/AA) unable to undergo autocleavage at the well-characterized G670/G671 diglycine motif, and four USP1 mutants identified in tumor samples that cluster around this cleavage site (G667A, L669P, K673T and A676T). Using cell-based assays, we have determined the ability of these mutants to bind UAF1, to reverse DNA damage-induced monoubiquitination of PCNA, and to undergo autocleavage. Results: A non-phosphorylatable S313A mutant of USP1 retained the ability to bind UAF1 and to reverse PCNA ubiquitination in cell-based assays. Regardless of the presence of a phosphomimetic S313D mutation, deletion of USP1 fragment 420-520 disrupted UAF1 binding, as determined using a nuclear relocation assay. The UAF1 binding site in a second UAF1-interacting DUB, USP46, was mapped to a region homologous to USP1(420-520). Regarding USP1 autocleavage, co-expression of the C90S and GG/AA mutants did not result in cleavage, while the cancer-associated mutation L669P was found to reduce cleavage efficiency. Conclusions: USP1 phosphorylation at S313 is not critical for PCNA deubiquitination, neither for binding to UAF1 in a cellular environment. In this context, USP1 amino acid motif 420-520 is necessary and sufficient for UAF1 binding. This motif, and a homologous amino acid segment that mediates USP46 binding to UAF1, map to the Fingers sub-domain of these DUBs. On the other hand, our results support the view that USP1 autocleavage may occur in cis, and can be altered by a cancer-associated mutation.