Large shocks vs. small shocks. (Or does size matter? May be so.)

What are the shocks that drive economic fluctuations? The answer to this question requires as a first step solving the shock identification issue. This paper proposes a new identification scheme based on two aspects: the long-run effect of the shock (permanent or transitory), and the size of the shock (Large or small). This is done by using a threshold integrated moving average model (TIMA) previously introduced in the literature by the authors. Based on this model we develop a testing strategy to determine whether Large and small shocks have different long-run effects, as well as whether one of them is purely transitory. The paper analyzes the impulse response function of both types of shocks, and provides the asymptotic results sufficient to implement the above testing strategy. Based on these results we develop a new nonlinear permanent–transitory decomposition, that is applied to US stock prices to analyze the quality ofthe stock market, and to US GNP to investigate the asymmetric behavior of its shocks.Publicad

The Automatic External Cardioverter-Defibrillator

In-hospital cardiac arrest remains a major problem but new technologies allowing fully automatic external defibrillation are available. These technologies allow the concept of “external therapeutic monitoring” of lethal arrhythmias. Since early defibrillation improves outcome by decreasing morbidity and mortality, the use of this device should improve the outcome of in-hospital cardiac arrest victims. Furthermore, the use of these devices could allow safe monitoring and treatment of patients at risk of cardiac arrest who not necessarily must be in conventional monitoring units (Intensive or Coronary Care Units) saving costs with a more meaningful use of resources. The capability to provide early defibrillation within any patient-care areas should be considered as an obligation (“standard of care”) of the modern hospital

Study of membrane proteome of DGKΖ-deficient cytotoxic T lymphocites

Tesis doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Ciencias, Departamento de Biología Molecular. Fecha de lectura: 11-10-2019Esta tesis tiene embargado el acceso al texto completo hasta el 11-04-2021T cells are key cells in the coordination and implementation of the adaptive immune response. Specifically, cytotoxic T lymphocytes are responsible for eliminating cells presenting antigens on their surface either viral or tumor type. After antigen presentation, these cells must undergo a series of changes in the pattern of protein expression to reinforce the signaling capability and allow movement to the site of action. In case of membrane proteins, there are changes in expression of surface receptors in order to receive chemical signals in the form of cytokines and other molecules, and also in adhesion molecules to allow the exit of the secondary lymphoid organs towards periphery. However, tumor cells can avoid CTL action in some cases, using escape mechanisms which limit their cytotoxic activity. Signaling by diacylglycerol (DAG) plays an essential role in antigen presentation. Diacylglycerol kinase (DGK) enzymes family negatively regulates this response by phosphorylation of DAG into phosphatidic acid (PA). ζ isoform (DGKζ) deficient mice CTL show increased activation and better response to tumors. Furthermore, DGKζ deficiency has been associated with changes in protein expression on the cell surface related to cell adhesion. Determining the role of DGKζ deficiency in cell surface protein expression pattern can help to understand key aspects like its effects in tumor elimination. In order to better understand the role of the DAG in CTL response, a proteomic study was designed to analyze the expression of proteins of these cells, with special interest in plasma membrane proteins. Firstly, a method of protein enrichment of the plasma membrane by biotinylation was optimized in Jurkat T cells, while other strategies such as subcellular fractionations were also tested to obtain better results. This method was then used with CTL, and changes in the expression pattern of membrane proteins dependent of DAG were studied by adding a phorbol ester (PMA) or by analyzing CTL obtained from DGKζ-deficient mice. To complete this study, a quantitative proteomics analysis was performed by SILAC labeling to determine significant quantitative changes in protein expression from DGKζ-deficient CTL. The results showed a higher expression of cytotoxic components such as granzyme B in the membrane fraction of DGKζ-/- CTL.Los linfocitos T son células fundamentales en la coordinación y ejecución de la respuesta inmune adaptativa. En concreto, los linfocitos T citotóxicos (CTL) se encargan de la eliminación de células infectadas por patógenos intracelulares o células tumorales que presentan en su superficie antígenos específicos. Tras la activación, los CTL experimentan una serie de cambios en el patrón de expresión de proteínas que les permiten aumentar su capacidad de señalización y su desplazamiento hacia los sitios de acción. En el caso de las proteínas de membrana presentan cambios en la expresión de receptores de citocinas y moléculas de adhesión. Sin embargo, las células diana tumorales en algunos casos son capaces de eludir la acción de los CTL mediante mecanismos de evasión que limitan su capacidad efectora. La señalización del diacilglicerol (DAG) juega un papel esencial durante la activación de los linfocitos T. La familia de enzimas de las diacilglicerol quinasas (DGK) regula negativamente esta respuesta mediante la fosforilación del DAG y su conversión en ácido fosfatídico (PA). Los CTL de ratones deficientes en la isoforma DGKζ muestran una mayor activación y una mejor respuesta frente a tumores. Además, la deficiencia en DGKζ se ha asociado a cambios en la expresión de proteínas de la superficie celular relacionadas con la adhesión celular. Determinar cómo la deficiencia de DGKζ afecta al patrón de expresión de proteínas de superficie puede ayudar a entender fenómenos como su mayor eficiencia en la eliminación de tumores. Para comprender mejor el papel de DGKζ en la respuesta de las CTL, diseñamos una aproximación proteómica para caracterizar las proteínas expresadas en su superficie celular. En primer lugar se optimizó en células T Jurkat un método de enriquecimiento de proteínas de la membrana plasmática mediante biotinilación, a la vez que se ensayaron otras estrategias como fraccionamientos subcelulares para obtener mejores rendimientos. Después se empleó este método con CTL, y se estudiaron los cambios en el patrón de expresión de proteínas de membrana dependientes del DAG mediante la adición de un éster de forbol (PMA) o el análisis de CTL obtenidos a partir de ratones deficientes en DGKζ. Para completar el estudio se realizó un análisis de proteómica cuantitativa mediante marcaje SILAC para determinar cambios cuantitativos significativos en proteínas expresadas en CTL de ratones deficientes en DGKζ. Los resultados arrojaron una mayor expresión de componentes citotóxicos como granzima B en la fracción de membranas de CTL DGKζ-/-.La realización de esta tesis ha sido posible gracias a una beca de Formación del Profesorado Universitario (FPU) del Ministerio de Educación, Cultura y Deport

Vote-boosting ensembles

Vote-boosting is a sequential ensemble learning method in which the individual classifiers are built on different weighted versions of the training data. To build a new classifier, the weight of each training instance is determined in terms of the degree of disagreement among the current ensemble predictions for that instance. For low class-label noise levels, especially when simple base learners are used, emphasis should be made on instances for which the disagreement rate is high. When more flexible classifiers are used and as the noise level increases, the emphasis on these uncertain instances should be reduced. In fact, at sufficiently high levels of class-label noise, the focus should be on instances on which the ensemble classifiers agree. The optimal type of emphasis can be automatically determined using cross-validation. An extensive empirical analysis using the beta distribution as emphasis function illustrates that vote-boosting is an effective method to generate ensembles that are both accurate and robust

Understanding the ex-ante cost of liquidity in the limit order book: a note.

El presente trabajo estima una nueva medida de coste de liquidez de los activos financieros en un mercado dirigido por órdenes. Esta medida, denominada función de liquidez, recoge el coste ex-ante de comprar y vender simultáneamente una determinada cantidad de acciones haciendo uso de toda la información ofrecida por el libro de órdenes. De esta manera se superan las dificultades que la consideración por separado de la horquilla de precios o la profundidad ocasiona sobre la caracterización de la liquidez de los diferentes activos.This paper estimates a new measure of liquidity costs in a market driven by orders. It represents the cost of simultaneously buying and selling a given amount of shares, and it is given by a single measure of ex-ante liquidity that aggregates all available information in the limit order book for a given number of shares. The cost of liquidity is an increasing function relating bid-ask spreads with the amounts available for trading. This measure completely characterizes the cost of liquidity of any given asset. It does not suffer from the usual ambiguities related to either the bid-ask spread or depth when they are considered separately. On the contrary, with a single measure, we are able to capture all dimensions of liquidity costs on ex-ante basis.Función de liquidez; Coste de liquidez; Libro de órdenes límite; Horquilla de precios; Profundidad; liquidity function; liquidity cost; open limit order book; bid-ask spread; depth;