Validación de las quinasas de estrés p38MAPKs como nuevos biomarcadores tumorales : Análisis de su papel en cáncer de colon asociado a colitis

Tesis doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Ciencias, Departamento de Biología Molecular. Fecha de lectura: 23-10-2019Esta tesis tiene embargado el acceso al texto completo hasta el 23-04-2021Colon cancer is the third leading cause of death. The risk of develop colon cancer is significantly increased with chronic inflammation form 2% to 30% along the years. In our lab it has been studied the role of p38γ and p38δ in the development of cancer associated to colitis. We described that the incidence of cancer associated to colitis is decreased with the knockout of p38γ and p38δ. It has also been described that p38γ and p38δ have both pro-tumorigenic and anti-tumorigenic roles in tumour development and progression. It is cause p38γ and p38δ could play different biological function depending on the cellular context. We decided to study the role of p38γ and p38δ in two different compartments related to cancer associated to colitis, by using two different conditional mice: The VillinCre-p38γ/δ-/- (which have a deletion of p38γ and p38δ in the intestinal epithelial cells) and the LysCre-p38γ/δ-/- (which have a deletion of p38γ and p38δ in the myeloid cells). We found that deletion of p38γ and p38δ in the intestinal epithelial cells increase tumor formation, in parallel with an increase in inflammatory cytokine induction, while the deletion of p38γ and p38δ in the myeloid cells decrease tumor formation, with higher apoptotic levels. VillinCre-p38γ/δ-/- mice tumours showed more monocyte myeloid derived suppressor cells. We also found that deletion of p38γ and p38δ in the intestinal epithelial cells enhance the severity of colitis pathology, with increased epithelial damage, inflammatory cytokine induction, and IGFBP-3 and osteopontin production. In the other hand, the deletion p38γ and p38δ in the myeloid cells protects the intestinal epithelium against the damage in colitis. Analysis of immune cell populations in LysCre-p38γ/δ-/- mice showed increase macrophages, neutrophils and CD4+ T cells in colon during colitis, and increase CD4+ T cells in tumours during colitis associated cancer models. Together, our results describe that p38γ and p38δ play different roles in the development of colitis or colitis associated cancer, depending on the cellular conte

Currency Hedging Strategies Using Dynamic Multivariate GARCH

This paper examines the effect on the effectiveness of using futures contracts as hedging instruments of: 1) the model of volatility used to estimate conditional variances and covariances, 2) the analyzed currency, and 3) the maturity of the futures contract being used. For this purpose, daily data of futures and spot exchange rates of three currencies, Euro, British pound and Japanese yen, against the American dollar are used to analyze hedge ratios and hedging effectiveness resulting from using two different maturity currency contracts, near-month and next-to-near-month contract. We estimate four multivariate volatility models (CCC, VARMA-AGARCH, DCC and BEKK) and calculate optimal portfolio weights and optimal hedge ratios to identify appropriate currency hedging strategies. Hedging effectiveness index suggests that the best results in terms of reducing the variance of the portfolio are for the USD/GBP exchange rate. The results show that futures hedging strategies are slightly more effective when the near-month future contract is used for the USD/GBP and USD/JPY currencies. Moreover, CCC and AGARCH models provide similar hedging effectiveness although some differences appear when the DCC and BEKK models are used.Multivariate GARCH, conditional correlations, exchange rates, optimal hedge ratio, optimal portfolio weights, hedging strategies.

Tertiary of Central System basins

The rise of the Central System due to reactivation of late Hercynian fault systems during the Alpine Orogeny directly affected the strcture and stratigraphic framework of the basins nearby that were being filled al the same time. The sedimentary record is the essential key to understanding the tectonic and palaeo-morphological history, of the Central Range, and vice-versa. Relating the filling of the basins with the definition of the mountain range, pre-arkosic, arkosic and post-arkosic stages have been proposed. However, it is difficult to support the previous idea that the arkosic stage continued throughout the Late Tertiary to finish in Middle Pliocene.: times withe the deposition of the Paramos(limestone). The arkoscs of the Central System arc of Eocene-Oligocce age and the highest alluvial fan deposits may be of Aragonian age. There is only a poor record of the remaining Tertiary and Quaternary sediments. boeause of active river incision during this lime in the hasins, the ranges and elsewhere in the Spanish Meseta

Educación matemática realista en educación infantil: “redescubriendo el teatro Calderón de Valladolid”

A partir de la pregunta de investigación ¿cómo contribuyen los contextos realistas en la enseñanza aprendizaje de las matemáticas en Educación Infantil?, se presenta un estudio cuyos objetivos han sido: a) diseñar una práctica docente para niños de 5 años desde la perspectiva de la Educación Matemática Realista (EMR); b) analizar los aprendizajes matemáticos que realizan los alumnos en el contexto de dicha práctica

Currency hedging strategies, strategic benchmarks and the Global and Euro Sovereign financial crises

This paper investigates dynamic currency hedging benefits, with a further focus on the impact of currency hedging before and during the recent financial crises originated from the subprime and the Euro sovereign bonds. We take the point of view of a Euro-based institutional investor who considers passive investment strategies in portfolios holding European, British and US assets. We analyze the impact of the model specification to improve the risk-return tradeoff when currency risk is hedged. Hedging strategies of currency risk, using exchange rates futures and driven by several multivariate GARCH models, depend on the portfolio composition and period analyzed. Dynamic covariance models provide limited evidences of a decrease in hedging rations compared to naïve hedging strategies based on linear regressions or variance smoothing. Nevertheless, those results are coupled with better performances of dynamic covariance models in terms of hedging effectiveness an improved Sharpe ratios. The empirical evidences are observed both in-sample as well as in an out-of-sample exercise

El paleógeno del sector suroccidental de la Cuenca del Duero: nueva división estratigráfica y controles sobre su sedimentación

Como resultado de un detallado trabajo cartográfico, estratigráfico y sedimentológico, se propone la división del Paleógeno del sector suroccidental de la Cuenca del Duero en cuatro U.T.S. limitadas por discordancias. Estas D.T.S., que abarcan desde el tránsito Cretácico superior-Paleoceno hasta el Oligoceno, incluyen distintas unidades litoestratigráficas que sonreordenadas, modificando la sucesión estratigrática propuesta por los autores anteriores. Se asigna a la U.T.S. Me una edad Cretácico superior-Paleoceno. Se individualiza el Eoceno inferior (U.T.S. PI) en la zona de Salamanca. Se reinterpreta la relación existente entre los materiales del Eoceno mediosuperior y los del Eoceno superior-Oligoceno considerándolos en tránsito por lo que se asignan a una única U.T.S. (UT.S. P2, Eoceno medio Oligoceno inferior). Se incluyen en la U.T.S. P3 (Oligoceno superior) los sedimentos arcósicos anterionnente considerados como Vatlesienses. Así mismo, se considera que gran parte de los materiales asignados al mioceno inferior son sedimentos paleógenos afectados por un proceso de alteración de edad Miocena, lo que implica una variación en la extensión y límites de la cuenca neógena en su extremo SO. Se analiza la evolución de las distintas U.T.S. deduciendo un carácter tectónico para las megasecuencias propuestas relacionado con el progresivo levantamiento de las áreas fuente. El clima muestra un tránsito desde condiciones tropicales sin estaciones contrastadas (U,T.S. MC) hasta un clima mediterráneo árido (U.T.S. P3) con una estación seca muy marcada y una corta estación húmeda caracterizada por violentas avenidas. [ABSTRACT] A Paleogene four-fold stratigraphical division is proposed here as result fram the detailed studies carried out during the elaboration of 22 sheets of the Geological Map of Spain (E. 1 :50.000). This units (T.S.U.) are limited by regional discordances and they have a Upper Cretaceous to Oligocene ages. The previous stratigraphical schemes are rearranged due to the different stratigraphical relations observed between the lithostratigraphical units proposed by other workers (Jiménez, 1970; Corrochano, 1977; Alonso, 1981...). An Upper Cretaceous-Paleocene age is assumed to T.S.U. MC which is mainly composed by siliciclastic sediments strongly silicified forming a FU megasequence. It is intcrpretated as braided streams that flowed downslope filling paleovalleys erodcd onto Paleozoic materiaIs. Mineralogical features point to a tropical climate. Lower Eocene (T.S.U. P I ) is identified in the Salamanca area, where ir was considered as lacking. It is composed by arkosic sediments forming a CU megasequence. Fossil faunas of this T.S.U. record a subtropical clima te. It is observed a transition from high sinuosity streams to braided ones. T.S.U. P2 (Middle Eocene-Lower Oligocene) is composed of two lithostratigraphical units previously considered as bounded by a discordance (Alonso, 1981).It has a subarkosic to lithic nature and forms a CU megasequence. This unit records a subtropical climate with short arid periods and is interpretated as braided streams showing an increasing stability and enviromental energy to the topo T.S. U. P3 (Upper Oligocene) is composed by arkosic sediments previously considered of Vallesian (Middle to Upper Miocene) age. They form a CU megasequence that records braided streams prograding basinwardfrom higher arcas. Palinological associations and pedological features indicate an arid mediterranean climate with long arid periods and a short rainy season with strong floods. We consider that most of Lower Miocene sediments are of Paleogene age. They are afected by a widespread alteration profile developed along Lower Miocene that masked its more significative features. Sedimentological analysis of T.S.U. shows that its megasequentiality is related to the rates of tectonical uplift of source arcas whereas a distensive regime developed in the sedimentation basin

Reversibility of Symmetric Linear Cellular Automata with Radius r = 3

The aim of this work is to completely solve the reversibility problem for symmetric linear cellular automata with radius r = 3 and null boundary conditions. The main result obtained is the explicit computation of the local transition functions of the inverse cellular automata. This allows introduction of possible and interesting applications in digital image encryption.This research was funded by Ministerio de Ciencia, Innovación y Universidades (MCIU, Spain), Agencia Estatal de Investigación (AEI, Spain), and Fondo Europeo de Desarrollo Regional (FEDER, UE) under project TIN2017-84844-C2-2-R (MAGERAN) and project SA054G18 supported by Consejería de Educación (Junta de Castilla y León, Spain)

Alpine tectonic framework of south-western Duero basin

The tectonic activity in the south-western area of the Spanish Northern Meseta (Ciudad Rodrigo and Duero basins) during most of the Tertiary was determined by u transpressive regime that reactivated Hercynian to Late-Hercynian faults. The record of the Alpine Orogeny is complex because the sedimentary record indicates a compresive regime in the sour e areas coeval with the extensionall to transpresive regime indicated by normal or strike-slip faults. This duality is due 10 the geotectonics position of this area between two compressive areas, the Cantabrian Range and the Central System, and the extensional Atlantic margin

North-western Cainozoic record: present knowledge and the correlation problem

Tertiary deposits of the north-western Iberian Peninsula are heterogeneous because they occur in several morpho-structural positions as isolated and dispersed basins and outerops. The quality of the palaeontological record is usually very poor and there are scarce data. Correlation depends on a wide range of criteria which arc not always equivalent: palaeontology, mineralogy and petrology, geomorphology, tectonics and comparison with better-known and better-dated facies in regions nearby. The results lack homogeneity and there arc notable discrepancie