Characterization of surface winds over the Iberian Peninsula

This work presents a characterization of the surface wind climatology over the Iberian Peninsula (IP). For this objective, an unprecedented observational database has been developed. The database covers a period of 6years (2002–2007) and consists of hourly wind speed and wind direction data recorded at 514 automatic weather stations. Theoriginal observations underwent a quality control process to remove rough errors from the data set. In the first step, the annual and seasonal mean behaviour of the wind field are presented. This analysis shows the high spatial variability of the wind as a result of its interaction with the main orographic features of the IP. In order to simplify the characterization of the wind, a clustering procedure was applied to group the observational sites with similar temporal wind variability. A total of 20 regions are identified. These regions are strongly related to the main landforms of the IP. The wind behaviour of each region, characterized by the wind rose (WR), annual cycle (AC) and wind speed histogram, is explained as the response of each region to the main circulation types (CTs) affecting the IP. Results indicate that the seasonal variability of the synoptic scale is related with intra-annual variability and modulated by local features in the WRs variability. The wind speed distribution not always fit to a unimodal Weibull distribution consequence of interactions at different atmospheric scales. This work contributes to a deeper understanding of the temporal and spatial variability of surface winds. Taken together, the wind database created, the methodology used and the conclusion extracted are a benchmark for future works based on the wind behaviour.

Rigor mortis at the myocardium investigated by post-mortem magnetic resonance imaging

INTRODUCTION Post-mortem cardiac MR exams present with different contraction appearances of the left ventricle in cardiac short axis images. It was hypothesized that the grade of post-mortem contraction may be related to the post-mortem interval (PMI) or cause of death and a phenomenon caused by internal rigor mortis that may give further insights in the circumstances of death. METHOD AND MATERIALS The cardiac contraction grade was investigated in 71 post-mortem cardiac MR exams (mean age at death 52y, range 12-89y; 48 males, 23 females). In cardiac short axis images the left ventricular lumen volume as well as the left ventricular myocardial volume were assessed by manual segmentation. The quotient of both (LVQ) represents the grade of myocardial contraction. LVQ was correlated to the PMI, sex, age, cardiac weight, body mass and height, cause of death and pericardial tamponade when present. In cardiac causes of death a separate correlation was investigated for acute myocardial infarction cases and arrhythmic deaths. RESULTS LVQ values ranged from 1.99 (maximum dilatation) to 42.91 (maximum contraction) with a mean of 15.13. LVQ decreased slightly with increasing PMI, however without significant correlation. Pericardial tamponade positively correlated with higher LVQ values. Variables such as sex, age, body mass and height, cardiac weight and cause of death did not correlate with LVQ values. There was no difference in LVQ values for myocardial infarction without tamponade and arrhythmic deaths. CONCLUSION Based on the observation in our investigated cases, the phenomenon of post-mortem myocardial contraction cannot be explained by the influence of the investigated variables, except for pericardial tamponade cases. Further research addressing post-mortem myocardial contraction has to focus on other, less obvious factors, which may influence the early post-mortem phase too.

Characterization of Enhancing MS Lesions by Dynamic Texture Parameter Analysis of Dynamic Susceptibility Perfusion Imaging

Purpose. The purpose of this study was to investigate statistical differences with MR perfusion imaging features that reflect the dynamics of Gadolinium-uptake in MS lesions using dynamic texture parameter analysis (DTPA). Methods. We investigated 51 MS lesions (25 enhancing, 26 nonenhancing lesions) of 12 patients. Enhancing lesions () were prestratified into enhancing lesions with increased permeability (EL+; ) and enhancing lesions with subtle permeability (EL−; ). Histogram-based feature maps were computed from the raw DSC-image time series and the corresponding texture parameters were analyzed during the inflow, outflow, and reperfusion time intervals. Results. Significant differences () were found between EL+ and EL− and between EL+ and nonenhancing inactive lesions (NEL). Main effects between EL+ versus EL− and EL+ versus NEL were observed during reperfusion (mainly in mean and standard deviation (SD): EL+ versus EL− and EL+ versus NEL), while EL− and NEL differed only in their SD during outflow. Conclusion. DTPA allows grading enhancing MS lesions according to their perfusion characteristics. Texture parameters of EL− were similar to NEL, while EL+ differed significantly from EL− and NEL. Dynamic texture analysis may thus be further investigated as noninvasive endogenous marker of lesion formation and restoration.

DEVELOPMENT OF A BEAM-SPECIFIC PLANNING TARGET VOLUME AND A ROBUST PLAN ANALYSIS TOOL FOR PROTON THERAPY

Proton therapy is growing increasingly popular due to its superior dose characteristics compared to conventional photon therapy. Protons travel a finite range in the patient body and stop, thereby delivering no dose beyond their range. However, because the range of a proton beam is heavily dependent on the tissue density along its beam path, uncertainties in patient setup position and inherent range calculation can degrade thedose distribution significantly. Despite these challenges that are unique to proton therapy, current management of the uncertainties during treatment planning of proton therapy has been similar to that of conventional photon therapy. The goal of this dissertation research was to develop a treatment planning method and a planevaluation method that address proton-specific issues regarding setup and range uncertainties. Treatment plan designing method adapted to proton therapy: Currently, for proton therapy using a scanning beam delivery system, setup uncertainties are largely accounted for by geometrically expanding a clinical target volume (CTV) to a planning target volume (PTV). However, a PTV alone cannot adequately account for range uncertainties coupled to misaligned patient anatomy in the beam path since it does not account for the change in tissue density. In order to remedy this problem, we proposed a beam-specific PTV (bsPTV) that accounts for the change in tissue density along the beam path due to the uncertainties. Our proposed method was successfully implemented, and its superiority over the conventional PTV was shown through a controlled experiment.. Furthermore, we have shown that the bsPTV concept can be incorporated into beam angle optimization for better target coverage and normal tissue sparing for a selected lung cancer patient. Treatment plan evaluation method adapted to proton therapy: The dose-volume histogram of the clinical target volume (CTV) or any other volumes of interest at the time of planning does not represent the most probable dosimetric outcome of a given plan as it does not include the uncertainties mentioned earlier. Currently, the PTV is used as a surrogate of the CTV’s worst case scenario for target dose estimation. However, because proton dose distributions are subject to change under these uncertainties, the validity of the PTV analysis method is questionable. In order to remedy this problem, we proposed the use of statistical parameters to quantify uncertainties on both the dose-volume histogram and dose distribution directly. The robust plan analysis tool was successfully implemented to compute both the expectation value and its standard deviation of dosimetric parameters of a treatment plan under the uncertainties. For 15 lung cancer patients, the proposed method was used to quantify the dosimetric difference between the nominal situation and its expected value under the uncertainties.

Determinación del color de aceites de oliva vírgenes (Mendoza-Argentina)

El color es un criterio básico en la evaluación de la calidad del aceite de oliva virgen y constituye una cualidad fundamental en el análisis sensorial. Este nuevo parámetro de calidad del aceite de oliva virgen puede verse afectado por la variedad y el grado de madurez de la aceituna, la zona de producción, el proceso de obtención y la conservación. Debido a la importancia que actualmente tiene la tipificación de los alimentos (por ejemplo en las denominaciones de origen), surge la necesidad de conocer el color del aceite de oliva virgen. Para su determinación se utilizaron dos métodos analíticos: la escala ABT modificada (Azul de Bromotimol) y el colorímetro HunterLab. Los resultados muestran que el cociente a/b constituye un parámetro adecuado para comparar y clasificar aceites de oliva vírgenes y brinda una mayor información en la comercialización de este producto.

Part of the global DOC versus AOU (dissolved organic carbon/apparent oxygen utilization) data compilation, Southern Ocean

Recent evidence that dissolved organic carbon (DOC) is a significant component of the organic carbon flux below the photic layer of the ocean (1), together with verification of high respiration rates in the dark ocean (2), suggests that the downward flux of DOC may play a major role in supporting respiration there. Here we show, on the basis of examination of the relation between DOC and apparent oxygen utilization (AOU), that the DOC flux supports ~10% of the respiration in the dark ocean. The contribution of DOC to pelagic respiration below the surface mixed layer can be inferred from the relation between DOC and apparent oxygen utilization (AOU, µM O2), a variable quantifying the cumulative oxygen consumption since a water parcel was last in contact with the atmosphere. However, assessments of DOC/AOU relations have been limited to specific regions of the ocean (3, 4) and have not considered the global ocean. We assembled a large data set (N = 9824) of concurrent DOC and AOU observations collected in cruises conducted throughout the world's oceans (fig. S1, table S1) to examine the relative contribution of DOC to AOU and, therefore, respiration in the dark ocean. AOU increased from an average (±SE) 96.3 ± 2.0 µM at the base of the surface mixed layer (100 m) to 165.5 ± 4.3 µM at the bottom of the main thermocline (1000 m), with a parallel decline in the average DOC from 53.5 ± 0.2 to 43.4 ± 0.3 µM C (Fig. 1). In contrast, there is no significant decline in DOC with increasing depth beyond 1000 m depth (Fig. 1), indicating that DOC exported with overturning circulation plays a minor role in supporting respiration in the ocean interior (5). Assuming a molar respiratory quotient of 0.69, the decline in DOC accounts for 19.6 ± 0.4% of the AOU within the top 1000 m (Fig. 1). This estimate represents, however, an upper limit, because the correlation between DOC and AOU is partly due to mixing of DOC-rich warm surface waters with DOC-poor cold thermocline waters (6). Removal of this effect by regressing DOC against AOU and water temperature indicates that DOC supports only 8.4 ± 0.3% of the respiration in the mesopelagic waters.

Respiration and ingestion rates of calanoid copepod in the northern Benguela Current System measured ex situ during the RSS Discovery D356 cruise in 2010

Respiration rates of 16 calanoid copepod species from the northern Benguela upwelling system were measured on board RRS Discovery in September/October 2010 to determine their energy requirements and assess their significance in the carbon cycle. Copepod species were sampled by different net types. Immediately after the hauls, samples were sorted to species and stages (16 species; females, males and C5 copepodids) according to Bradford-Grieve et al. (1999). Specimens were kept in temperature-controlled refrigerators for at least 12 h before they were used in experiments. Respiration rates of different copepod species were measured onboard by optode respirometry (for details see Köster et al., 2008) with a 10-channel optode respirometer (PreSens Precision Sensing Oxy-10 Mini, Regensburg, Germany) under simulated in situ conditions in temperature-controlled refrigerators. Experiments were run in gas-tight glass bottles (12-13 ml). For each set of experiments, two controls without animals were measured under exactly the same conditions to compensate for potential bias. The number of animals per bottle depended on the copepods size, stage and metabolic activity. Animals were not fed during the experiments but they showed natural species-specific movements. Immediately after the experiments, all specimens were deep-frozen at - 80 °C for later dry mass determination (after lyophilisation for 48 h) in the home lab. The carbon content (% of dry mass) of each species was measured by mass-spectrometry in association with stable isotope analysis and body dry mass was converted to units of carbon. For species without available carbon data, the mean value of all copepod species (44% dry mass) was applied. For the estimation of carbon requirements of copepod species, individual oxygen consumption rates were converted to carbon units, assuming that the expiration of 1 ml oxygen mobilises 0.44 mg of organic carbon by using a respiratory quotient (RQ) of 0.82 for a mixed diet consisting of proteins (RQ = 0.8-1.0), lipids (RQ = 0.7) and carbohydrates (RQ = 1.0) (Auel and Werner, 2003). The carbon ingestion rates were calculated using the energy budget and the potential maximum ingestion rate approach. To allow for physiological comparisons of respiration rates of deep- and shallow-living copepod species without the effects of ambient temperature and different individual body mass, individual respiration rates were temperature- (15°C, Q10=2) and size-adjusted. The scaling coefficient of 0.76 (R2=0.556) is used for the standardisation of body dry mass to 0.3 mg (mean dry mass of all analysed copepods), applying the allometric equation R= (R15°C/M0.76)×0.30.76, where R is respiration and M is individual dry mass in mg.

Increased CO2 modifies the carbon balance and the photosynthetic yield of two common Arctic brown seaweeds: Desmarestia aculeata and Alaria esculenta

Ocean acidification affects with special intensity Arctic ecosystems, being marine photosynthetic organisms a primary target, although the consequences of this process in the carbon fluxes of Arctic algae are still unknown. The alteration of the cellular carbon balance due to physiological acclimation to an increased CO2 concentration (1300 ppm) in the common Arctic brown seaweeds Desmarestia aculeata and Alaria esculenta from Kongsfjorden (Svalbard) was analysed. Growth rate of D. aculeata was negatively affected by CO2 enrichment, while A. esculenta was positively affected, as a result of a different reorganization of the cellular carbon budget in both species. Desmarestia aculeata showed increased respiration, enhanced accumulation of storage biomolecules and elevated release of dissolved organic carbon, whereas A. esculenta showed decreased respiration and lower accumulation of storage biomolecules. Gross photosynthesis (measured both as O2 evolution and 14C fixation) was not affected in any of them, suggesting that photosynthesis was already saturated at normal CO2 conditions and did not participate in the acclimation response. However, electron transport rate changed in both species in opposite directions, indicating different energy requirements between treatments and species specificity. High CO2 levels also affected the N-metabolism, and 13C isotopic discrimination values from algal tissue pointed to a deactivation of carbon concentrating mechanisms. Since increased CO2 has the potential to modify physiological mechanisms in different ways in the species studied, it is expected that this may lead to changes in the Arctic seaweed community, which may propagate to the rest of the food web.

An Oka principle for equivariant isomorphisms

Let G be a reductive complex Lie group acting holomorphically on normal Stein spaces X and Y, which are locally G-biholomorphic over a common categorical quotient Q. When is there a global G-biholomorphism X → Y? If the actions of G on X and Y are what we, with justification, call generic, we prove that the obstruction to solving this local-to-global problem is topological and provide sufficient conditions for it to vanish. Our main tool is the equivariant version of Grauert's Oka principle due to Heinzner and Kutzschebauch. We prove that X and Y are G-biholomorphic if X is K-contractible, where K is a maximal compact subgroup of G, or if X and Y are smooth and there is a G-diffeomorphism ψ : X → Y over Q, which is holomorphic when restricted to each fibre of the quotient map X → Q. We prove a similar theorem when ψ is only a G-homeomorphism, but with an assumption about its action on G-finite functions. When G is abelian, we obtain stronger theorems. Our results can be interpreted as instances of the Oka principle for sections of the sheaf of G-biholomorphisms from X to Y over Q. This sheaf can be badly singular, even for a low-dimensional representation of SL2(ℂ). Our work is in part motivated by the linearisation problem for actions on ℂn. It follows from one of our main results that a holomorphic G-action on ℂn, which is locally G-biholomorphic over a common quotient to a generic linear action, is linearisable.

Input-Output Based Economic Impact Evaluation System for Small City Development: A Case Study on Saemangeum's Flux City Design

The paper aims to develop a quasi-dynamic interregional input-output model for evaluating the macro-economic impacts of small city development. The features of the model are summarized as follows: (1) the consumption expenditure of households is regarded as an endogenous variable, (2) the technological change is determined by the change of industrial Location Quotient caused by firm's investment activities. (3) a strong feedback function between the city design and the economic analysis is provided. For checking the performance of the model, Saemangeum's Flux City Design Plan is used as the simulation target in our paper.

Industrial agglomeration in Costa Rica : a descriptive analysis

This paper investigates the current situation of industrial agglomeration in Costa Rica, utilizing firm-level panel data for the period 2008-2012. We calculated Location Quotient and Theil Index based on employment by industry and found that 14 cantons have the industrial agglomerations for 9 industries. The analysis is in line with the nature of specific industries, the development of areas of concentration around free zones, and the evolving participation of Costa Rica in GVCs.

Digital image processing techniques as a tool for evaluating and mapping patinas on granite monuments

Monument conservation is related to the interaction between the original petrological parameters of the rock and external factors in the area where the building is sited, such as weather conditions, pollution, and so on. Depending on the environmental conditions and the characteristics of the materials used, different types of weathering predominate. In all, the appearance of surface crusts constitutes a first stage, whose origin can often be traced to the properties of the material itself. In the present study, different colours of “patinas” were distinguished by defining the threshold levels of greys associated with “pathology” in the histogram. These data were compared to background information and other parameters, such as mineralogical composition, porosity, and so on, as well as other visual signs of deterioration. The result is a map of the pathologies associated with “cover films” on monuments, which generate images by relating colour characteristics to desired properties or zones of interest.

Projector Model for Efficient List-Mode Reconstruction in PET Scanners with Parallel Planar Detectors

We have developed a new projector model specifically tailored for fast list-mode tomographic reconstructions in Positron emission tomography (PET) scanners with parallel planar detectors. The model provides an accurate estimation of the probability distribution of coincidence events defined by pairs of scintillating crystals. This distribution is parameterized with 2D elliptical Gaussian functions defined in planes perpendicular to the main axis of the tube of response (TOR). The parameters of these Gaussian functions have been obtained by fitting Monte Carlo simulations that include positron range, acolinearity of gamma rays, as well as detector attenuation and scatter effects. The proposed model has been applied efficiently to list-mode reconstruction algorithms. Evaluation with Monte Carlo simulations over a rotating high resolution PET scanner indicates that this model allows to obtain better recovery to noise ratio in OSEM (ordered-subsets, expectation-maximization) reconstruction, if compared to list-mode reconstruction with symmetric circular Gaussian TOR model, and histogram-based OSEM with precalculated system matrix using Monte Carlo simulated models and symmetries.

Segmentación de la glotis en imágenes laríngeas usando snakes.

El presente trabajo describe una nueva metodología para la detección automática del espacio glotal de imágenes laríngeas tomadas a partir de 15 vídeos grabados por el servicio ORL del hospital Gregorio Marañón de Madrid con luz estroboscópica. El sistema desarrollado está basado en el modelo de contornos activos (snake). El algoritmo combina en el pre-procesado, algunas técnicas tradicionales (umbralización y filtro de mediana) con técnicas más sofisticadas tales como filtrado anisotrópico. De esta forma, se obtiene una imagen apropiada para el uso de las snakes. El valor escogido para el umbral es del 85% del pico máximo del histograma de la imagen; sobre este valor la información de los píxeles no es relevante. El filtro anisotrópico permite distinguir dos niveles de intensidad, uno es el fondo y el otro es la glotis. La inicialización se basa en obtener el módulo del campo GVF; de esta manera se asegura un proceso automático para la selección del contorno inicial. El rendimiento del algoritmo se valida usando los coeficientes de Pratt y se compara contra una segmentación realizada manualmente y otro método automático basado en la transformada de watershed. SUMMARY: The present work describes a new methodology for the automatic detection of the glottal space from laryngeal images taken from 15 videos recorded by the ENT service of the Gregorio Marañon Hospital in Madrid with videostroboscopic equipment. The system is based on active contour models (snakes). The algorithm combines for the pre-processing, some traditional techniques (thresholding and median filter) with more sophisticated techniques such as anisotropic filtering. In this way, we obtain an appropriate image for the use of snake. The value selected for the threshold is 85% of the maximum peak of the image histogram; over this point the information of the pixels is not relevant. The anisotropic filter permits to distinguish two intensity levels, one is the background and the other one is the glottis. The initialization is based on the obtained magnitude by GVF field; in this manner an automatic process for the initial contour selection will be assured. The performance of the algorithm is tested using the Pratt coefficient and compared against a manual segmentation and another automatic method based on the watershed transformation.

Oscillatory genetic circuits: new designs and mathematical models

Introduction and motivation: A wide variety of organisms have developed in-ternal biomolecular clocks in order to adapt to cyclic changes of the environment. Clock operation involves genetic networks. These genetic networks have to be mod¬eled in order to understand the underlying mechanism of oscillations and to design new synthetic cellular clocks. This doctoral thesis has resulted in two contributions to the fields of genetic clocks and systems and synthetic biology, generally. The first contribution is a new genetic circuit model that exhibits an oscillatory behav¬ior through catalytic RNA molecules. The second and major contribution is a new genetic circuit model demonstrating that a repressor molecule acting on the positive feedback of a self-activating gene produces reliable oscillations. First contribution: A new model of a synthetic genetic oscillator based on a typical two-gene motif with one positive and one negative feedback loop is pre¬sented. The originality is that the repressor is a catalytic RNA molecule rather than a protein or a non-catalytic RNA molecule. This catalytic RNA is a ribozyme that acts post-transcriptionally by binding to and cleaving target mRNA molecules. This genetic clock involves just two genes, a mRNA and an activator protein, apart from the ribozyme. Parameter values that produce a circadian period in both determin¬istic and stochastic simulations have been chosen as an example of clock operation. The effects of the stochastic fluctuations are quantified by a period histogram and autocorrelation function. The conclusion is that catalytic RNA molecules can act as repressor proteins and simplify the design of genetic oscillators. Second and major contribution: It is demonstrated that a self-activating gene in conjunction with a simple negative interaction can easily produce robust matically validated. This model is comprised of two clearly distinct parts. The first is a positive feedback created by a protein that binds to the promoter of its own gene and activates the transcription. The second is a negative interaction in which a repressor molecule prevents this protein from binding to its promoter. A stochastic study shows that the system is robust to noise. A deterministic study identifies that the oscillator dynamics are mainly driven by two types of biomolecules: the protein, and the complex formed by the repressor and this protein. The main conclusion of this study is that a simple and usual negative interaction, such as degradation, se¬questration or inhibition, acting on the positive transcriptional feedback of a single gene is a sufficient condition to produce reliable oscillations. One gene is enough and the positive transcriptional feedback signal does not need to activate a second repressor gene. At the genetic level, this means that an explicit negative feedback loop is not necessary. Unlike many genetic oscillators, this model needs neither cooperative binding reactions nor the formation of protein multimers. Applications and future research directions: Recently, RNA molecules have been found to play many new catalytic roles. The first oscillatory genetic model proposed in this thesis uses ribozymes as repressor molecules. This could provide new synthetic biology design principles and a better understanding of cel¬lular clocks regulated by RNA molecules. The second genetic model proposed here involves only a repression acting on a self-activating gene and produces robust oscil¬lations. Unlike current two-gene oscillators, this model surprisingly does not require a second repressor gene. This result could help to clarify the design principles of cellular clocks and constitute a new efficient tool for engineering synthetic genetic oscillators. Possible follow-on research directions are: validate models in vivo and in vitro, research the potential of second model as a genetic memory, investigate new genetic oscillators regulated by non-coding RNAs and design a biosensor of positive feedbacks in genetic networks based on the operation of the second model Resumen Introduccion y motivacion: Una amplia variedad de organismos han desarro-llado relojes biomoleculares internos con el fin de adaptarse a los cambios ciclicos del entorno. El funcionamiento de estos relojes involucra redes geneticas. El mo delado de estas redes geneticas es esencial tanto para entender los mecanismos que producen las oscilaciones como para diseiiar nuevos circuitos sinteticos en celulas. Esta tesis doctoral ha dado lugar a dos contribuciones dentro de los campos de los circuitos geneticos en particular, y biologia de sistemas y sintetica en general. La primera contribucion es un nuevo modelo de circuito genetico que muestra un comportamiento oscilatorio usando moleculas de ARN cataliticas. La segunda y principal contribucion es un nuevo modelo de circuito genetico que demuestra que una molecula represora actuando sobre el lazo de un gen auto-activado produce oscilaciones robustas. Primera contribucion: Es un nuevo modelo de oscilador genetico sintetico basado en una tipica red genetica compuesta por dos genes con dos lazos de retroa-limentacion, uno positivo y otro negativo. La novedad de este modelo es que el represor es una molecula de ARN catalftica, en lugar de una protefna o una molecula de ARN no-catalitica. Este ARN catalitico es una ribozima que actua despues de la transcription genetica uniendose y cortando moleculas de ARN mensajero (ARNm). Este reloj genetico involucra solo dos genes, un ARNm y una proteina activadora, aparte de la ribozima. Como ejemplo de funcionamiento, se han escogido valores de los parametros que producen oscilaciones con periodo circadiano (24 horas) tanto en simulaciones deterministas como estocasticas. El efecto de las fluctuaciones es-tocasticas ha sido cuantificado mediante un histograma del periodo y la función de auto-correlacion. La conclusion es que las moleculas de ARN con propiedades cataliticas pueden jugar el misnio papel que las protemas represoras, y por lo tanto, simplificar el diseno de los osciladores geneticos. Segunda y principal contribucion: Es un nuevo modelo de oscilador genetico que demuestra que un gen auto-activado junto con una simple interaction negativa puede producir oscilaciones robustas. Este modelo ha sido estudiado y validado matematicamente. El modelo esta compuesto de dos partes bien diferenciadas. La primera parte es un lazo de retroalimentacion positiva creado por una proteina que se une al promotor de su propio gen activando la transcription. La segunda parte es una interaction negativa en la que una molecula represora evita la union de la proteina con el promotor. Un estudio estocastico muestra que el sistema es robusto al ruido. Un estudio determinista muestra que la dinamica del sistema es debida principalmente a dos tipos de biomoleculas: la proteina, y el complejo formado por el represor y esta proteina. La conclusion principal de este estudio es que una simple y usual interaction negativa, tal como una degradation, un secuestro o una inhibition, actuando sobre el lazo de retroalimentacion positiva de un solo gen es una condition suficiente para producir oscilaciones robustas. Un gen es suficiente y el lazo de retroalimentacion positiva no necesita activar a un segundo gen represor, tal y como ocurre en los relojes actuales con dos genes. Esto significa que a nivel genetico un lazo de retroalimentacion negativa no es necesario de forma explicita. Ademas, este modelo no necesita reacciones cooperativas ni la formation de multimeros proteicos, al contrario que en muchos osciladores geneticos. Aplicaciones y futuras lineas de investigacion: En los liltimos anos, se han descubierto muchas moleculas de ARN con capacidad catalitica. El primer modelo de oscilador genetico propuesto en esta tesis usa ribozimas como moleculas repre¬soras. Esto podria proporcionar nuevos principios de diseno en biologia sintetica y una mejor comprension de los relojes celulares regulados por moleculas de ARN. El segundo modelo de oscilador genetico propuesto aqui involucra solo una represion actuando sobre un gen auto-activado y produce oscilaciones robustas. Sorprendente-mente, un segundo gen represor no es necesario al contrario que en los bien conocidos osciladores con dos genes. Este resultado podria ayudar a clarificar los principios de diseno de los relojes celulares naturales y constituir una nueva y eficiente he-rramienta para crear osciladores geneticos sinteticos. Algunas de las futuras lineas de investigation abiertas tras esta tesis son: (1) la validation in vivo e in vitro de ambos modelos, (2) el estudio del potential del segundo modelo como circuito base para la construction de una memoria genetica, (3) el estudio de nuevos osciladores geneticos regulados por ARN no codificante y, por ultimo, (4) el rediseno del se¬gundo modelo de oscilador genetico para su uso como biosensor capaz de detectar genes auto-activados en redes geneticas.