The E2F2 Transcription Factor Sustains Hepatic Glycerophospholipid Homeostasis in Mice

Increasing evidence links metabolic signals to cell proliferation, but the molecular wiring that connects the two core machineries remains largely unknown. E2Fs are master regulators of cellular proliferation. We have recently shown that E2F2 activity facilitates the completion of liver regeneration after partial hepatectomy (PH) by regulating the expression of genes required for S-phase entry. Our study also revealed that E2F2 determines the duration of hepatectomy-induced hepatic steatosis. A transcriptomic analysis of normal adult liver identified "lipid metabolism regulation" as a major E2F2 functional target, suggesting that E2F2 has a role in lipid homeostasis. Here we use wild-type (E2F2(+/+)) and E2F2 deficient (E2F2(-/-)) mice to investigate the in vivo role of E2F2 in the composition of liver lipids and fatty acids in two metabolically different contexts: quiescence and 48-h post-PH, when cellular proliferation and anabolic demands are maximal. We show that liver regeneration is accompanied by large triglyceride and protein increases without changes in total phospholipids both in E2F2(+/+) and E2F2(-/-) mice. Remarkably, we found that the phenotype of quiescent liver tissue from E2F2(-/-) mice resembles the phenotype of proliferating E2F2(+/+) liver tissue, characterized by a decreased phosphatidylcholine to phosphatidylethanolamine ratio and a reprogramming of genes involved in generation of choline and ethanolamine derivatives. The diversity of fatty acids in total lipid, triglycerides and phospholipids was essentially preserved on E2F2 loss both in proliferating and non-proliferating liver tissue, although notable exceptions in inflammation-related fatty acids of defined phospholipid classes were detected. Overall, our results indicate that E2F2 activity sustains the hepatic homeostasis of major membrane glycerolipid components while it is dispensable for storage glycerolipid balance.

Valuation of Wind Energy Projects: A Real Options Approach

We address the valuation of an operating wind farm and the finite-lived option to invest in it under different reward/support schemes: a constant feed-in tariff, a premium on top of the electricity market price (either a fixed premium or a variable subsidy such as a renewable obligation certificate or ROC), and a transitory subsidy, among others. Futures contracts on electricity with ever longer maturities enable market-based valuations to be undertaken. The model considers up to three sources of uncertainty: the electricity price, the level of wind generation, and the certificate (ROC) price where appropriate. When analytical solutions are lacking, we resort to a trinomial lattice combined with Monte Carlo simulation; we also use a two-dimensional binomial lattice when uncertainty in the ROC price is considered. Our data set refers to the UK. The numerical results show the impact of several factors involved in the decision to invest: the subsidy per MWh generated, the initial lump-sum subsidy, the maturity of the investment option, and electricity price volatility. Different combinations of variables can help bring forward investments in wind generation. One-off policies, e.g., a transitory initial subsidy, seem to have a stronger effect than a fixed premium per MWh produced.

Two-Stage Stochastic Optimization. An Application in the Third Sector

[en] It is known that most of the problems applied in the real life present uncertainty. In the rst part of the dissertation, basic concepts and properties of the Stochastic Programming have been introduced to the reader, also known as Optimization under Uncertainty. Moreover, since stochastic programs are complex to compute, we have presented some other models such as wait-and-wee, expected value and the expected result of using expected value. The expected value of perfect information and the value of stochastic solution measures quantify how worthy the Stochastic Programming is, with respect to the other models. In the second part, it has been designed and implemented with the modeller GAMS and the optimizer CPLEX an application that optimizes the distribution of non-perishable products, guaranteeing some nutritional requirements with minimum cost. It has been developed within Hazia project, managed by Sortarazi association and associated with Food Bank of Biscay and Basic Social Services of several districts of Biscay.

The Evaluation of Fisheries Management: A Dynamic Stochastic Approach

In this article, we analyze how to evaluate fishery resource management under “ecological uncertainty”. In this context, an efficient policy consists of applying a different exploitation rule depending on the state of the resource and we could say that the stock is always in transition, jumping from one steady state to another. First, we propose a method for calibrating the growth path of the resource such that observed dynamics of resource and captures are matched. Second, we apply the calibration procedure proposed in two different fishing grounds: the European Anchovy (Division VIII) and the Southern Stock of Hake. Our results show that the role played by uncertainty is essential for the conclusions. For European Anchovy fishery (Division VIII) we find, in contrast with Del Valle et al. (2001), that this is not an overexploited fishing ground. However, we show that the Southern Stock of Hake is in a dangerous situation. In both cases our results are in accordance with ICES advice.

The Economics of Gasification: A Market-Based Approach

This paper deals with the economics of gasification facilities in general and IGCC power plants in particular. Regarding the prospects of these systems, passing the technological test is one thing, passing the economic test can be quite another. In this respect, traditional valuations assume constant input and/or output prices. Since this is hardly realistic, we allow for uncertainty in prices. We naturally look at the markets where many of the products involved are regularly traded. Futures markets on commodities are particularly useful for valuing uncertain future cash flows. Thus, revenues and variable costs can be assessed by means of sound financial concepts and actual market data. On the other hand, these complex systems provide a number of flexibility options (e.g., to choose among several inputs, outputs, modes of operation, etc.). Typically, flexibility contributes significantly to the overall value of real assets. Indeed, maximization of the asset value requires the optimal exercise of any flexibility option available. Yet the economic value of flexibility is elusive, the more so under (price) uncertainty. And the right choice of input fuels and/or output products is a main concern for the facility managers. As a particular application, we deal with the valuation of input flexibility. We follow the Real Options approach. In addition to economic variables, we also address technical and environmental issues such as energy efficiency, utility performance characteristics and emissions (note that carbon constraints are looming). Lastly, a brief introduction to some stochastic processes suitable for valuation purposes is provided.

Economía de la salud, modalidades de evaluación económica

La salud es un aspecto muy importante en la vida de cualquier persona, de forma que, al ocurrir cualquier contingencia que merma el estado de salud de un individuo o grupo de personas, se debe valorar estrictamente y en detalle las distintas alternativas destinadas a combatir la enfermedad. Esto se debe a que, la calidad de vida de los pacientes variará dependiendo de la alternativa elegida. La calidad de vida relacionada con la salud (CVRS) se entiende como el valor asignado a la duración de la vida, modificado por la oportunidad social, la percepción, el estado funcional y la disminución provocadas por una enfermedad, accidente, tratamiento o política (Sacristán et al, 1995). Para determinar el valor numérico asignado a la CVRS, ante una intervención, debemos beber de la teoría económica aplicada a las evaluaciones sanitarias para nuevas intervenciones. Entre los métodos de evaluación económica sanitaria, el método coste-utilidad emplea como utilidad, los años de vida ajustado por calidad (AVAC), que consiste, por un lado, tener en cuenta la calidad de vida ante una intervención médica, y por otro lado, los años estimados a vivir tras la intervención. Para determinar la calidad de vida, se emplea técnicas como el Juego Estándar, la Equivalencia Temporal y la Escala de Categoría. Estas técnicas nos proporcionan un valor numérico entre 0 y 1, siendo 0 el peor estado y 1 el estado perfecto de salud. Al entrevistar a un paciente a cerca de la utilidad en términos de salud, puede haber riesgo o incertidumbre en la pregunta planteada. En tal caso, se aplica el Juego Estándar con el fin de determinar el valor numérico de la utilidad o calidad de vida del paciente ante un tratamiento dado. Para obtener este valor, al paciente se le plantean dos escenarios: en primer lugar, un estado de salud con probabilidad de morir y de sobrevivir, y en segundo lugar, un estado de certeza. La utilidad se determina modificando la probabilidad de morir hasta llegar a la probabilidad que muestra la indiferencia del individuo entre el estado de riesgo y el estado de certeza. De forma similar, tenemos la equivalencia temporal, cuya aplicación resulta más fácil que el juego estándar ya que valora en un eje de ordenadas y abscisas, el valor de la salud y el tiempo a cumplir en esa situación ante un tratamiento sanitario, de forma que, se llega al valor correspondiente a la calidad de vida variando el tiempo hasta que el individuo se muestre indiferente entre las dos alternativas. En último lugar, si lo que se espera del paciente es una lista de estados de salud preferidos ante un tratamiento, empleamos la Escala de Categoría, que consiste en una línea horizontal de 10 centímetros con puntuaciones desde 0 a 100. La persona entrevistada coloca la lista de estados de salud según el orden de preferencia en la escala que después es normalizado a un intervalo entre 0 y 1. Los años de vida ajustado por calidad se obtienen multiplicando el valor de la calidad de vida por los años de vida estimados que vivirá el paciente. Sin embargo, ninguno de estas metodologías mencionadas consideran el factor edad, siendo necesario la inclusión de esta variable. Además, los pacientes pueden responder de manera subjetiva, situación en la que se requiere la opinión de un experto que determine el nivel de discapacidad del aquejado. De esta forma, se introduce el concepto de años de vida ajustado por discapacidad (AVAD) tal que el parámetro de utilidad de los AVAC será el complementario del parámetro de discapacidad de los AVAD Q^i=1-D^i. A pesar de que este último incorpora parámetros de ponderación de edad que no se contemplan en los AVAC. Además, bajo la suposición Q=1-D, podemos determinar la calidad de vida del individuo antes del tratamiento. Una vez obtenido los AVAC ganados, procedemos a la valoración monetaria de éstos. Para ello, partimos de la suposición de que la intervención sanitaria permite al individuo volver a realizar las labores que venía realizando. De modo que valoramos los salarios probables con una temporalidad igual a los AVAC ganados, teniendo en cuenta la limitación que supone la aplicación de este enfoque. Finalmente, analizamos los beneficios derivados del tratamiento (masa salarial probable) si empleamos la tabla GRF-95 (población femenina) y GRM-95 (población masculina).

Robust Sliding Control of SEIR Epidemic Models

This paper is aimed at designing a robust vaccination strategy capable of eradicating an infectious disease from a population regardless of the potential uncertainty in the parameters defining the disease. For this purpose, a control theoretic approach based on a sliding-mode control law is used. Initially, the controller is designed assuming certain knowledge of an upper-bound of the uncertainty signal. Afterwards, this condition is removed while an adaptive sliding control system is designed. The closed-loop properties are proved mathematically in the nonadaptive and adaptive cases. Furthermore, the usual sign function appearing in the sliding-mode control is substituted by the saturation function in order to prevent chattering. In addition, the properties achieved by the closed-loop system under this variation are also stated and proved analytically. The closed-loop system is able to attain the control objective regardless of the parametric uncertainties of the model and the lack of a priori knowledge on the system.