Genetische Analyse des Somatostatin-Systems

Somatostatin ist ein Molekül mit multifunktinonellem Charakter, dem Neurotransmitter-, Neuromodulator- und (Neuro)-Hormoneigenschaften zugeschrieben werden. Gemäß seiner ubiquitären Verteilung in Geweben beeinflusst es Stoffwechsel- und Entwicklungsprozesse, bis hin zu Lern-und Gedächtnisleistungen. Diese Wirkungen resultieren aus dem lokalen und zeitlichen Zusammenspiel eines Liganden und fünf G-Protein gekoppelter Rezeptoren (SSTR1-5). Zur Charakterisierung der biologischen Bedeutung des Somatostatin-Systems im Gesamtorganismus wurde eine Mutationsanalyse einzelner Systemkomponenten durchgeführt. Sie umfaßte die Inaktivierung der Gene für das Somatostatin-Präpropeptid und die der Rezeptoren SSTR3 und SSTR4 durch Gene Targeting. Die entsprechenden Ausfallmutationen belegen: Weder die Rezeptoren 3 und 4, noch Somatostatin sind für das Überleben des Organismus unter Standardhaltungsbedingungen notwendig. Die entsprechenden Mauslinien zeigen keine unmittelbar auffälligen Einschränkungen ihrer Biologie. Die Somatostatin-Nullmaus wurde zum Hauptgegenstand einer detaillierten Untersuchung aufgrund der übergeordneten Position des Liganden in der Signalkaskade und verfügbaren Hinweisen zu seiner Funktion. Folgende Schlußfolgerungen konnten nach eingehender Analyse gezogen werden: Der Ausfall des Somatostatin-Gens hat erhöhte Plasmakonzentrationen an Wachstumshormon (GH) zur Konsequenz. Dies steht im Einklang mit der Rolle Somatostatins als hemmender Faktor der Wachstumshormon-Freisetzung, die in der Mutante aufgehoben ist. Durch die Somatostatin-Nullmaus wurde zudem deutlich: Somatostatin interagiert als wesentliches Bindeglied zwischen der Wachstums- und Streßachse. Permanent erhöhte Corticosteron-Werte in den Mutanten implizieren einen negativen tonischen Einfluß für die Sekretion von Glukocorticoiden in vivo. Damit zeigt die Knockout-Maus, daß Somatostatin normalerweise als ein entscheidendes inhibierendes Kontrollelement der Steroidfreisetzung fungiert. Verhaltensversuche offenbarten ein Defizit im motorischen Lernen. Somatostatin-Nullmäuse bleiben im Lernparadigma “Rotierender Stabtest” hinter ihren Artgenossen zurück ohne aber generell in Motorik oder Koordination eingeschränkt zu sein. Diese motorischen Lernvorgänge sind von einem funktionierenden Kleinhirn abhängig. Da Somatostatin und seine Rezeptoren kaum im adulten, wohl aber im sich entwickelnden Kleinhirn auftreten, belegt dieses Ergebnis die Funktion transient in der Entwicklung exprimierter Neuropeptide – eine lang bestehende, aber bislang experimentell nicht nachgewiesene Hypothese. Die Überprüfung weiterer physiologischer Parameter und Verhaltenskategorien unter Standard-Laborbedingunggen ergab keine sichtbaren Abweichungen im Vergleich zu Wildtyp-Mäusen. Damit steht nun ein Tiermodell zur weiterführenden Analyse für die Somatostatin-Forschung bereit: In endokrinologischen, elektrophysiologischen und verhaltens-biologischen Experimenten ist nun eine unmittelbare Korrelation selektiv mit dem Somatostatin-Peptid bzw. mit den Rezeptoren 3 und 4 aber auch in Kombination der Ausfallmutationen nach entsprechenden Kreuzungen möglich.

Hypersonic phonon propagation in mesoscopic systems by Brillouin spectroscopy

Phononic crystals, capable to block or direct the propagation of elastic/acoustic waves, have attracted increasing interdisciplinary interest across condensed matter physics and materials science. As of today, no generalized full description of elastic wave propagation in phononic structures is available, mainly due to the large number of variables determining the band diagram. Therefore, this thesis aims for a deeper understanding of the fundamental concepts governing wave propagation in mesoscopic structures by investigation of appropriate model systems. The phononic dispersion relation at hypersonic frequencies is directly investigated by the non-destructive technique of high-resolution spontaneous Brillouin light scattering (BLS) combined with computational methods. Due to the vector nature of the elastic wave propagation, we first studied the hypersonic band structure of hybrid superlattices. These 1D phononic crystals composed of alternating layers of hard and soft materials feature large Bragg gaps. BLS spectra are sensitive probes of the moduli, photo-elastic constants and structural parameters of the constituent components. Engineering of the band structure can be realized by introduction of defects. Here, cavity layers are employed to launch additional modes that modify the dispersion of the undisturbed superlattice, with extraordinary implications to the band gap region. Density of states calculations in conjunction with the associated deformation allow for unambiguous identication of surface and cavity modes, as well as their interaction with adjacent defects. Next, the role of local resonances in phononic systems is explored in 3D structures based on colloidal particles. In turbid media BLS records the particle vibration spectrum comprising resonant modes due to the spatial confinement of elastic energy. Here, the frequency and lineshapes of the particle eigenmodes are discussed as function of increased interaction and departure from spherical symmetry. The latter is realized by uniaxial stretching of polystyrene spheres, that can be aligned in an alternating electric field. The resulting spheroidal crystals clearly exhibit anisotropic phononic properties. Establishing reliable predictions of acoustic wave propagation, necessary to advance, e.g., optomechanics and phononic devices is the ultimate aim of this thesis.

Strong Local Passivity in Finite Quantum Systems

Passive states of quantum systems are states from which no system energy can be extracted by any cyclic (unitary) process. Gibbs states of all temperatures are passive. Strong local (SL) passive states are defined to allow any general quantum operation, but the operation is required to be local, being applied only to a specific subsystem. Any mixture of eigenstates in a system-dependent neighborhood of a nondegenerate entangled ground state is found to be SL passive. In particular, Gibbs states are SL passive with respect to a subsystem only at or below a critical system-dependent temperature. SL passivity is associated in many-body systems with the presence of ground state entanglement in a way suggestive of collective quantum phenomena such as quantum phase transitions, superconductivity, and the quantum Hall effect. The presence of SL passivity is detailed for some simple spin systems where it is found that SL passivity is neither confined to systems of only a few particles nor limited to the near vicinity of the ground state.

Metaheuristics for the Order Batching Problem in Manual Order Picking Systems

In manual order picking systems, order pickers walk or drive through a distribution warehouse in order to collect items which are requested by (internal or external) customers. In order to perform these operations efficiently, it is usually required that customer orders are combined into (more substantial) picking orders of limited size. The Order Batching Problem considered in this paper deals with the question of how a given set of customer orders should be combined such that the total length of all tours is minimized which are necessary to collect all items. The authors introduce two metaheuristic approaches for the solution of this problem: the first one is based on Iterated Local Search; the second on Ant Colony Optimization. In a series of extensive numerical experiments, the newly developed approaches are benchmarked against classic solution methods. It is demonstrated that the proposed methods are not only superior to existing methods but provide solutions which may allow distribution warehouses to be operated significantly more efficiently.

Water–montmorillonite systems: Neutron scattering and tracer throughdiffusion studies

Designs for deep geological respositories of nuclear waste include bentonite as a hydraulic and chemisorption buffer material to protect the biosphere from leakage of radionuclides. Bentonite is chosen because it is a cheap, naturally occurring material with the required properties. It consists essentially of montmorillonite, a swelling clay mineral. Upon contact with groundwater such clays can seal the repository by incorporating water in the interlayers of their crystalline structure. The intercalated water exhibits significantly different properties to bulk water in the surrounding interparticle pores, such as lower diffusion coefficients (González Sánchez et. al. 2008). This doctoral thesis presents water distribution and diffusion behavior on various time and space scales in montmorillonite. Experimental results are presented for Na- and Cs-montmorillonite samples with a range of bulk dry densities (0.8 to 1.7 g/cm3). The experimental methods employed were neutron scattering (backscattering, diffraction, time-of-flight), adsorption measurements (water, nitrogen) and tracer-through diffusion. For the tracer experiments the samples were fully saturated via the liquid phase under volume-constrained conditions. In contrast, for the neutron scattering experiments, the samples were hydrated via the vapor phase and subsequently compacted, leaving a significant fraction of interparticle pores unfilled with water. Owing to these differences in saturation, the water contents of the samples for neutron scattering were characterized by gravimetry whereas those for the tracer experiments were obtained from the bulk dry density. The amount of surface water in interlayer pores could be successfully discriminated from the amount of bulk-like water in interparticle pores in Na- and Csmontmorillonite using neutron spectroscopy. For the first time in the literature, the distribution of water between these two pore environments was deciphered as a function of gravimetric water content. The amount was compared to a geometrical estimation of the amount of interlayer and interparticle water determined by neutron diffraction and adsorption measurements. The relative abundances of the 1 to 4 molecular water layers in the interlayer were determined from the area ratios of the (001)-diffraction peaks. Depending on the characterization method, different fractions of surface water and interlayer water were obtained. Only surface and interlayer water exists in amontmorillonite with water contents up to 0.18 g/g according to spectroscopic measurements and up to 0.32 g/g according to geometrical estimations, respectively. At higher water contents, bulk-like and interparticle water also exists. The amounts increase monotonically, but not linearly, from zero to 0.33 g/g for bulk-like water and to 0.43 g/g for interparticle water. It was found that water most likely redistributes between the surface and interlayer sites during the spectroscopic measurements and therefore the reported fraction is relevant only below about -10 ºC (Anderson, 1967). The redistribution effect can explain the discrepancy in fractions between the methods. In a novel approach the fractions of water in different pore environments were treated as a fixed parameter to derive local diffusion coefficients for water from quasielastic neutron scattering data, in particular for samples with high water contents. Local diffusion coefficients were obtained for the 1 to 4 molecular water layers in the interlayer of 0.5·10–9, 0.9·10–9, 1.5·10–9 and 1.4·10–9 m²/s, respectively, taking account of the different water fractions (molecular water layer, bulk-like water). The diffusive transport of 22Na and HTO through Na-montmorillonite was measured on the laboratory experimental scale (i.e. cm, days) by tracer through-diffusion experiments. We confirmed that diffusion of HTO is independent of the ionic strength of the external solution in contact with the clay sample but dependent on the bulk dry density. In contrast, the diffusion of 22Na was found to depend on both the ionic strength of the pore solution and on the bulk dry density. The ratio of the pore and surface diffusion could be experimentally determined for 22Na from the dependence of the diffusion coefficient on the ionic strength. Activation energies were derived from the temperaturedependent diffusion coefficients via the Arrhenius relation. In samples with high bulk dry density the activation energies are slightly higher than those of bulk water whereas in low density samples they are lower. The activation energies as a function of ionic strengths of the pore solutions are similar for 22Na and HTO. The facts that (i) the slope of the logarithmic effective diffusion coefficients as a function of the logarithmic ionic strength is less than unity for low bulk dry densities and (ii) two water populations can be observed for high gravimetric water contents (low bulk dry densities) support the interlayer and interparticle porosity model proposed by Glaus et al. (2007), Bourg et al. (2006, 2007) and Gimmi and Kosakowski (2011).

New methods for the estimation of Takagi-Sugeno model based extended Kalman filter and its applications to optimal control for nonlinear systems

This paper describes new approaches to improve the local and global approximation (matching) and modeling capability of Takagi–Sugeno (T-S) fuzzy model. The main aim is obtaining high function approximation accuracy and fast convergence. The main problem encountered is that T-S identification method cannot be applied when the membership functions are overlapped by pairs. This restricts the application of the T-S method because this type of membership function has been widely used during the last 2 decades in the stability, controller design of fuzzy systems and is popular in industrial control applications. The approach developed here can be considered as a generalized version of T-S identification method with optimized performance in approximating nonlinear functions. We propose a noniterative method through weighting of parameters approach and an iterative algorithm by applying the extended Kalman filter, based on the same idea of parameters’ weighting. We show that the Kalman filter is an effective tool in the identification of T-S fuzzy model. A fuzzy controller based linear quadratic regulator is proposed in order to show the effectiveness of the estimation method developed here in control applications. An illustrative example of an inverted pendulum is chosen to evaluate the robustness and remarkable performance of the proposed method locally and globally in comparison with the original T-S model. Simulation results indicate the potential, simplicity, and generality of the algorithm. An illustrative example is chosen to evaluate the robustness. In this paper, we prove that these algorithms converge very fast, thereby making them very practical to use.

An optimization method for conceptual design in engineering systems based on high order singular value decomposition

Se presenta un nuevo método de diseño conceptual en Ingeniería Aeronáutica basado el uso de modelos reducidos, también llamados modelos sustitutos (‘surrogates’). Los ingredientes de la función objetivo se calculan para cada indiviudo mediante la utilización de modelos sustitutos asociados a las distintas disciplinas técnicas que se construyen mediante definiciones de descomposición en valores singulares de alto orden (HOSVD) e interpolaciones unidimensionales. Estos modelos sustitutos se obtienen a partir de un número limitado de cálculos CFD. Los modelos sustitutos pueden combinarse, bien con un método de optimización global de tipo algoritmo genético, o con un método local de tipo gradiente. El método resultate es flexible a la par que mucho más eficiente, computacionalmente hablando, que los modelos convencionales basados en el cálculo directo de la función objetivo, especialmente si aparecen un gran número de parámetros de diseño y/o de modelado. El método se ilustra considerando una versión simplificada del diseño conceptual de un avión. Abstract An optimization method for conceptual design in Aeronautics is presented that is based on the use of surrogate models. The various ingredients in the target function are calculated for each individual using surrogates of the associated technical disciplines that are constructed via high order singular value decomposition and one dimensional interpolation. These surrogates result from a limited number of CFD calculated snapshots. The surrogates are combined with an optimization method, which can be either a global optimization method such as a genetic algorithm or a local optimization method, such as a gradient-like method. The resulting method is both flexible and much more computationally efficient than the conventional method based on direct calculation of the target function, especially if a large number of free design parameters and/or tunablemodeling parameters are present. The method is illustrated considering a simplified version of the conceptual design of an aircraft empennage.

A new approach to fuzzy estimation of Takagi-Sugeno model and its applications to optimal control for nonlinear systems

An efficient approach is presented to improve the local and global approximation and modelling capability of Takagi-Sugeno (T-S) fuzzy model. The main aim is obtaining high function approximation accuracy. The main problem is that T-S identification method cannot be applied when the membership functions are overlapped by pairs. This restricts the use of the T-S method because this type of membership function has been widely used during the last two decades in the stability, controller design and are popular in industrial control applications. The approach developed here can be considered as a generalized version of T-S method with optimized performance in approximating nonlinear functions. A simple approach with few computational effort, based on the well known parameters' weighting method is suggested for tuning T-S parameters to improve the choice of the performance index and minimize it. A global fuzzy controller (FC) based Linear Quadratic Regulator (LQR) is proposed in order to show the effectiveness of the estimation method developed here in control applications. Illustrative examples of an inverted pendulum and Van der Pol system are chosen to evaluate the robustness and remarkable performance of the proposed method and the high accuracy obtained in approximating nonlinear and unstable systems locally and globally in comparison with the original T-S model. Simulation results indicate the potential, simplicity and generality of the algorithm.

Auto-localization algorithm for local positioning systems

This paper studies the problem of determining the position of beacon nodes in Local Positioning Systems (LPSs), for which there are no inter-beacon distance measurements available and neither the mobile node nor any of the stationary nodes have positioning or odometry information. The common solution is implemented using a mobile node capable of measuring its distance to the stationary beacon nodes within a sensing radius. Many authors have implemented heuristic methods based on optimization algorithms to solve the problem. However, such methods require a good initial estimation of the node positions in order to find the correct solution. In this paper we present a new method to calculate the inter-beacon distances, and hence the beacons positions, based in the linearization of the trilateration equations into a closed-form solution which does not require any approximate initial estimation. The simulations and field evaluations show a good estimation of the beacon node positions.

Distributed control strategies for photovoltaic systems in urban environments

Este trabajo es una contribución a los sistemas fotovoltaicos (FV) con seguimiento distribuido del punto de máxima potencia (DMPPT), una topología que se caracteriza porque lleva a cabo el MPPT a nivel de módulo, al contrario de las topologías más tradicionales que llevan a cabo el MPPT para un número más elevado de módulos, pudiendo ser hasta cientos de módulos. Las dos tecnologías DMPPT que existen en el mercado son conocidos como microinversores y optimizadores de potencia, y ofrecen ciertas ventajas sobre sistemas de MPPT central como: mayor producción en situaciones de mismatch, monitorización individual de cada módulo, flexibilidad de diseño, mayor seguridad del sistema, etc. Aunque los sistemas DMPPT no están limitados a los entornos urbanos, se ha enfatizado en el título ya que es su mercado natural, siendo difícil una justificación de su sobrecoste en grandes huertas solares en suelo. Desde el año 2010 el mercado de estos sistemas ha incrementado notablemente y sigue creciendo de una forma continuada. Sin embargo, todavía falta un conocimiento profundo de cómo funcionan estos sistemas, especialmente en el caso de los optimizadores de potencia, de las ganancias energéticas esperables en condiciones de mismatch y de las posibilidades avanzadas de diagnóstico de fallos. El principal objetivo de esta tesis es presentar un estudio completo de cómo funcionan los sistemas DMPPT, sus límites y sus ventajas, así como experimentos varios que verifican la teoría y el desarrollo de herramientas para valorar las ventajas de utilizar DMPPT en cada instalación. Las ecuaciones que modelan el funcionamiento de los sistemas FVs con optimizadores de potencia se han desarrollado y utilizado para resaltar los límites de los mismos a la hora de resolver ciertas situaciones de mismatch. Se presenta un estudio profundo sobre el efecto de las sombras en los sistemas FVs: en la curva I-V y en los algoritmos MPPT. Se han llevado a cabo experimentos sobre el funcionamiento de los algoritmos MPPT en situaciones de sombreado, señalando su ineficiencia en estas situaciones. Un análisis de la ventaja del uso de DMPPT frente a los puntos calientes es presentado y verificado. También se presenta un análisis sobre las posibles ganancias en potencia y energía con el uso de DMPPT en condiciones de sombreado y este también es verificado experimentalmente, así como un breve estudio de su viabilidad económica. Para ayudar a llevar a cabo todos los análisis y experimentos descritos previamente se han desarrollado una serie de herramientas software. Una siendo un programa en LabView para controlar un simulador solar y almacenar las medidas. También se ha desarrollado un programa que simula curvas I-V de módulos y generador FVs afectados por sombras y este se ha verificado experimentalmente. Este mismo programa se ha utilizado para desarrollar un programa todavía más completo que estima las pérdidas anuales y las ganancias obtenidas con DMPPT en instalaciones FVs afectadas por sombras. Finalmente, se han desarrollado y verificado unos algoritmos para diagnosticar fallos en sistemas FVs con DMPPT. Esta herramienta puede diagnosticar los siguientes fallos: sombras debido a objetos fijos (con estimación de la distancia al objeto), suciedad localizada, suciedad general, posible punto caliente, degradación de módulos y pérdidas en el cableado de DC. Además, alerta al usuario de las pérdidas producidas por cada fallo y no requiere del uso de sensores de irradiancia y temperatura. ABSTRACT This work is a contribution to photovoltaic (PV) systems with distributed maximum power point tracking (DMPPT), a system topology characterized by performing the MPPT at module level, instead of the more traditional topologies which perform MPPT for a larger number of modules. The two DMPPT technologies available at the moment are known as microinverters and power optimizers, also known as module level power electronics (MLPE), and they provide certain advantages over central MPPT systems like: higher energy production in mismatch situations, monitoring of each individual module, system design flexibility, higher system safety, etc. Although DMPPT is not limited to urban environments, it has been emphasized in the title as it is their natural market, since in large ground-mounted PV plants the extra cost is difficult to justify. Since 2010 MLPE have increased their market share steadily and continuing to grow steadily. However, there still lacks a profound understanding of how they work, especially in the case of power optimizers, the achievable energy gains with their use and the possibilities in failure diagnosis. The main objective of this thesis is to provide a complete understanding of DMPPT technologies: how they function, their limitations and their advantages. A series of equations used to model PV arrays with power optimizers have been derived and used to point out limitations in solving certain mismatch situation. Because one of the most emphasized benefits of DMPPT is their ability to mitigate shading losses, an extensive study on the effects of shadows on PV systems is presented; both on the I-V curve and on MPPT algorithms. Experimental tests have been performed on the MPPT algorithms of central inverters and MLPE, highlighting their inefficiency in I-V curves with local maxima. An analysis of the possible mitigation of hot-spots with DMPPT is discussed and experimentally verified. And a theoretical analysis of the possible power and energy gains is presented as well as experiments in real PV systems. A short economic analysis of the benefits of DMPPT has also been performed. In order to aide in the previous task, a program which simulates I-V curves under shaded conditions has been developed and experimentally verified. This same program has been used to develop a software tool especially designed for PV systems affected by shading, which estimates the losses due to shading and the energy gains obtained with DMPPT. Finally, a set of algorithms for diagnosing system faults in PV systems with DMPPT has been developed and experimentally verified. The tool can diagnose the following failures: fixed object shading (with distance estimation), localized dirt, generalized dirt, possible hot-spots, module degradation and excessive losses in DC cables. In addition, it alerts the user of the power losses produced by each failure and classifies the failures by their severity and it does not require the use of irradiance or temperature sensors.