Advanced applications of X-ray Absorption Spectroscopy to the study of protein metal sites.

We present a study of the metal sites of different proteins through X-ray Absorption Fine Structure (XAFS) spectroscopy. First of all, the capabilities of XAFS analysis have been improved by ab initio simulation of the near-edge region of the spectra, and an original analysis method has been proposed. The method subsequently served ad a tool to treat diverse biophysical problems, like the inhibition of proton-translocating proteins by metal ions and the matrix effect exerted on photosynthetic proteins (the bacterial Reaction Center, RC) by strongly dehydrate sugar matrices. A time-resolved study of Fe site of RC with μs resolution has been as well attempted. Finally, a further step aimed to improve the reliability of XAFS analysis has been performed by calculating the dynamical parameters of the metal binding cluster by means of DFT methods, and the theoretical result obtained for MbCO has been successfully compared with experimental data.

Caratterizzazione e generazione di segnali PWM per amplificatori in classe D ad alta efficienza

The convergence of information technology and consumer electronics towards battery powered portable devices has increased the interest in high efficiency, low dissipation amplifiers. Class D amplifiers are the state of the art in low power consumption and high performance amplification. In this thesis we explore the possibility of exploiting nonlinearities introduced by the PWM modulation, by designing an optimized modulation law which scales its carrier frequency adaptively with the input signal's average power while preserving the SNR, thus reducing power consumption. This is achieved by means of a novel analytical model of the PWM output spectrum, which shows how interfering harmonics and their bandwidth affect the spectrum. This allows for frequency scaling with negligible aliasing between the baseband spectrum and its harmonics. We performed low noise power spectrum measurements on PWM modulations generated by comparing variable bandwidth, random test signals with a variable frequency triangular wave carrier. The experimental results show that power-optimized frequency scaling is both feasible and effective. The new analytical model also suggests a new PWM architecture that can be applied to digitally encoded input signals which are predistorted and compared with a cosine carrier, which is accurately synthesized by a digital oscillator. This approach has been simulated in a realistic noisy model and tested in our measurement setup. A zero crossing search on the obtained PWM modulation law proves that this approach yields an equivalent signal quality with respect to traditional PWM schemes, while entailing the use of signals whose bandwidth is remarkably smaller due to the use of a cosine instead of a triangular carrier.

Messung der direkten CP-Verletzung mit dem NA48-Detektor

Das Ziel des Experiments NA48 am CERN ist die Messung des Parameters Re(epsilon'/epsilon) der direktenCP-Verletzung mit einer Genauigkeit von 2x10^-4. Experimentell zugänglich ist das DoppelverhältnisR, das aus den Zerfällen des KL und KS in zwei neutrale bzw. zwei geladene Pionengebildet wird. Für R gilt in guter Näherung: R=1-6Re(epsilon'/epsilon).
NA48 verwendet eine Wichtung der KL-Ereignisse zur Reduzierung der Sensitivität auf dieDetektorakzeptanz. Zur Kontrolle der bisherigen Standardanalyse wurde eine Analyse ohne Ereigniswichtung durchgeführt. Das Ergebnis derungewichteten Analyse wird in dieser Arbeit vorgestellt. Durch Verzicht auf die Ereigniswichtung kann derstatistische Anteil des Gesamtfehlers deutlich verringert werden. Da der limitierende Kanal der Zerfall deslanglebigen Kaons in zwei neutrale Pionen ist, ist die Verwendung der gesamten Anzahl derKL-Zerfälle ein lohnendes Ziel.Im Laufe dieser Arbeit stellte sich heraus, dass dersystematische Fehler der Akzeptanzkorrektur diesen Gewinn wieder aufhebt.

Das Ergebnis der Arbeit für die Daten aus den Jahren 1998und 1999 ohne Ereigniswichtung lautet
Re(epsilon'/epsilon)=(17,91+-4,41(syst.)+-1,36(stat.))x10^-4.
Damit ist eindeutig die Existenz der direkten CP-Verletzungbestätigt. Dieses Ergebnis ist mit dem veröffentlichten Ergebnis vonNA48 verträglichSomit ist der Test der bisherigen Analysestrategie bei NA48erfolgreich durchgeführt worden.

Valutazione dell'efficacia delle procedure di Pushover convenzionali, modali ed adattive applicate a telai piani in c.a. regolari ed irregolari in elevazione.

The research performed during the PhD and presented in this thesis, allowed to make judgments on pushover analysis method about its application in evaluating the correct structural seismic response. In this sense, the extensive critical review of existing pushover procedures (illustrated in chapter 1) outlined their major issues related to assumptions and to hypothesis made in the application of the method. Therefore, with the purpose of evaluate the effectiveness of pushover procedures, a wide numerical investigation have been performed. In particular the attention has been focused on the structural irregularity on elevation, on the choice of the load vector and on its updating criteria. In the study eight pushover procedures have been considered, of which four are conventional type, one is multi-modal, and three are adaptive. The evaluation of their effectiveness in the identification of the correct dynamic structural response, has been done by performing several dynamic and static non-linear analysis on eight RC frames, characterized by different proprieties in terms of regularity in elevation. The comparisons of static and dynamic results have then permitted to evaluate the examined pushover procedures and to identify the expected margin of error by using each of them. Both on base shear-top displacement curves and on considered storey parameters, the best agreement with the dynamic response has been noticed on Multi-Modal Pushover procedure. Therefore the attention has been focused on Displacement-based Adative Pushover, coming to define for it an improvement strategy, and on modal combination rules, advancing an innovative method based on a quadratic combination of the modal shapes (QMC). This latter has been implemented in a conventional pushover procedure, whose results have been compared with those obtained by other multi-modal procedures. The development of research on pushover analysis is very important because the objective is to come to the definition of a simple, effective and reliable analysis method, indispensable tool in the seismic evaluation of new or existing structures.

Kontaktmechanik und Strukturierung von festkörperunterstützen Lipidmembranen

Die vorliegende Arbeit beschreibt unter anderem die Realisierung eines Assays aus mikrostrukturierten und selektiv funktionalisierten künstlichen Membransegmenten auf einem Chip. Die Strukturierungsmethode kombiniert die softlithographische Technik des Mikroformens in Kapillaren mit der Vesikelspreittechnik und bietet ein elegantes Verfahren, einzeln adressierbare Lipidsegmente im Mikrometer Regime zu erzeugen. Unter Berücksichtigung des hydrodynamischen Fließverhaltens und der Stabilitätskriterien für PDMS-Elastomere wurden außerdem neue Strukturen entwi-ckelt, die für den kombinierten Einsatz von Rasterkraftmikroskopie und Fluoreszenz-mikroskopie optimiert sind. Die Anwendbarkeit des Lab-On-A-Chip-Devices als Bio-sensor wurde durch zwei prominente Protein-Rezeptor-Bindungsstudien fluores-zenzmikroskopisch und rasterkraftmikroskopisch belegt. Im zweiten Teil der Arbeit sind die mechanischen und adhäsiven Eigenschaften aus-gewählter Lipidsysteme mit einer neuen Charakterisierungstechnik untersucht wor-den, die die Kontaktmechanik von Rastersonden und Lipidmembranen auf Basis der Digitalisierung von Hochgeschwindigkeitskraftkurven und einer automatisierten Multi-parameteranalyse quantitativ erfasst. Dabei konnte die Korrelation zwischen der Ad-häsion und den materialspezifischen Durchbruchlängen und Durchbruchkräften, die charakteristische Stabilitätsparameter der Lipidmembran darstellen, auf Systemen mit variierenden Kopfgruppen und Kettenlängen analysiert werden. Das Verfahren erlaubte zudem die simultane Quantifizierung der elastischen Eigenschaften der Li-piddoppelschichten. Zu den Kraftkurven wurden Simulationen der Systemantwort durchgeführt, die ein tieferes Verständnis der Kontrastentstehung ermöglichen.

Thermal relaxation for particle systems in interaction with several bosonic heat reservoirs

The present thesis is concerned with the study of a quantum physical system composed of a small particle system (such as a spin chain) and several quantized massless boson fields (as photon gasses or phonon fields) at positive temperature. The setup serves as a simplified model for matter in interaction with thermal "radiation" from different sources. Hereby, questions concerning the dynamical and thermodynamic properties of particle-boson configurations far from thermal equilibrium are in the center of interest. We study a specific situation where the particle system is brought in contact with the boson systems (occasionally referred to as heat reservoirs) where the reservoirs are prepared close to thermal equilibrium states, each at a different temperature. We analyze the interacting time evolution of such an initial configuration and we show thermal relaxation of the system into a stationary state, i.e., we prove the existence of a time invariant state which is the unique limit state of the considered initial configurations evolving in time. As long as the reservoirs have been prepared at different temperatures, this stationary state features thermodynamic characteristics as stationary energy fluxes and a positive entropy production rate which distinguishes it from being a thermal equilibrium at any temperature. Therefore, we refer to it as non-equilibrium stationary state or simply NESS. The physical setup is phrased mathematically in the language of C*-algebras. The thesis gives an extended review of the application of operator algebraic theories to quantum statistical mechanics and introduces in detail the mathematical objects to describe matter in interaction with radiation. The C*-theory is adapted to the concrete setup. The algebraic description of the system is lifted into a Hilbert space framework. The appropriate Hilbert space representation is given by a bosonic Fock space over a suitable L2-space. The first part of the present work is concluded by the derivation of a spectral theory which connects the dynamical and thermodynamic features with spectral properties of a suitable generator, say K, of the time evolution in this Hilbert space setting. That way, the question about thermal relaxation becomes a spectral problem. The operator K is of Pauli-Fierz type. The spectral analysis of the generator K follows. This task is the core part of the work and it employs various kinds of functional analytic techniques. The operator K results from a perturbation of an operator L0 which describes the non-interacting particle-boson system. All spectral considerations are done in a perturbative regime, i.e., we assume that the strength of the coupling is sufficiently small. The extraction of dynamical features of the system from properties of K requires, in particular, the knowledge about the spectrum of K in the nearest vicinity of eigenvalues of the unperturbed operator L0. Since convergent Neumann series expansions only qualify to study the perturbed spectrum in the neighborhood of the unperturbed one on a scale of order of the coupling strength we need to apply a more refined tool, the Feshbach map. This technique allows the analysis of the spectrum on a smaller scale by transferring the analysis to a spectral subspace. The need of spectral information on arbitrary scales requires an iteration of the Feshbach map. This procedure leads to an operator-theoretic renormalization group. The reader is introduced to the Feshbach technique and the renormalization procedure based on it is discussed in full detail. Further, it is explained how the spectral information is extracted from the renormalization group flow. The present dissertation is an extension of two kinds of a recent research contribution by Jakšić and Pillet to a similar physical setup. Firstly, we consider the more delicate situation of bosonic heat reservoirs instead of fermionic ones, and secondly, the system can be studied uniformly for small reservoir temperatures. The adaption of the Feshbach map-based renormalization procedure by Bach, Chen, Fröhlich, and Sigal to concrete spectral problems in quantum statistical mechanics is a further novelty of this work.

Climate signatures in corals of the tropical-temperate transition zone (Late Miocene, Crete/Greece)

The present study describes a Late Miocene (early Tortonian - early Messinian) transitional carbonate system that combines elements of tropical and cool-water carbonate systems (Irakleion Basin, island of Crete, Greece). As documented by stratal geometries, the submarine topography of the basin was controlled by tilting blocks. Coral reefs formed by Porites and Tarbellastrea occurred in a narrow clastic coastal belt along a „central Cretan landmass“, and steep escarpments formed by faulting. Extensive covers of level-bottom communities existed in a low-energy environment on the gentle dip-slope ramps of the blocks that show the widest geographical distribution within the basin. Consistent patterns of landward and basinward shift of coastal onlap in all outcrop studies reveal an overriding control of 3rd and 4th order sea level changes on sediment dynamics and facies distributions over block movements. An increasingly dry climate and the complex submarine topography of the fault block mosaic kept sediment and nutrient discharge at a minimum. The skeletal limestone facies therefore reflects oligotrophic conditions and a sea surface temperature (SST) near the lower threshold temperature of coral reefs in a climatic position transitional between the tropical coral reef belt and the temperate zone. Stable isotope records (δ18O, δ13C) from massiv, exceptionally preserved Late Miocene aragonite coral skeletons reflect seasonal changes in sea surface temperature and symbiont autotrophy. Spectral analysis of a 69 years coral δ18O record reveals significant variance at interannual time scales (5-6 years) that matches the present-day eastern Mediterranean climate variability controlled by the Arctic Oscillation/North Atlantic Oscillation (AO/NAO), the Northern Hemisphere’s dominant mode of atmospheric variability. Supported by simulations with a complex atmospheric general circulation model coupled to a mixed-layer ocean model, it is suggested, that climate dynamics in the eastern Mediterranean and central Europe reflect atmospheric variability related to the Icelandic Low 10 million years ago. Usually, Miocene corals are transformed in calcite spar in geological time and isotope values are reset by diagenetic alteration. It is demonstrated that the relicts of growth bands represent an intriguing source of information for the growth conditions of fossil corals. Recrystallized growth bands were measured systematically in massive Porites from Crete. The Late Miocene corals were growing slowly with 2-4 mm/yr, compatible with present-day Porites from high latitude reefs, a relationship that fits the position of Crete at the margin of the Miocene tropical reef belt. Over Late Miocene time (Tortonian - early Messinian) growth rates remained remarkably constant, and if the modern growth temperature relationship for massive Porites applies to the Neogene, minimum (winter) SST did not exceed 19-21°C.

Accretion disk winds in active galactic nuclei: an X-ray view

This Thesis focuses on the X-ray study of the inner regions of Active Galactic Nuclei, in particular on the formation of high velocity winds by the accretion disk itself. Constraining AGN winds physical parameters is of paramount importance both for understanding the physics of the accretion/ejection flow onto supermassive black holes, and for quantifying the amount of feedback between the SMBH and its environment across the cosmic time. The sources selected for the present study are BAL, mini-BAL, and NAL QSOs, known to host high-velocity winds associated to the AGN nuclear regions. Observationally, a three-fold strategy has been adopted: - substantial samples of distant sources have been analyzed through spectral, photometric, and statistical techniques, to gain insights into their mean properties as a population; - a moderately sized sample of bright sources has been studied through detailed X-ray spectral analysis, to give a first flavor of the general spectral properties of these sources, also from a temporally resolved point of view; - the best nearby candidate has been thoroughly studied using the most sophisticated spectral analysis techniques applied to a large dataset with a high S/N ratio, to understand the details of the physics of its accretion/ejection flow. There are three main channels through which this Thesis has been developed: - [Archival Studies]: the XMM-Newton public archival data has been extensively used to analyze both a large sample of distant BAL QSOs, and several individual bright sources, either BAL, mini-BAL, or NAL QSOs. - [New Observational Campaign]: I proposed and was awarded with new X-ray pointings of the mini-BAL QSOs PG 1126-041 and PG 1351+640 during the XMM-Newton AO-7 and AO-8. These produced the biggest X-ray observational campaign ever made on a mini-BAL QSO (PG 1126-041), including the longest exposure so far. Thanks to the exceptional dataset, a whealth of informations have been obtained on both the intrinsic continuum and on the complex reprocessing media that happen to be in the inner regions of this AGN. Furthermore, the temporally resolved X-ray spectral analysis field has been finally opened for mini-BAL QSOs. - [Theoretical Studies]: some issues about the connection between theories and observations of AGN accretion disk winds have been investigated, through theoretical arguments and synthetic absorption line profiles studies.

Comparison between analytical and numerical methods for the assessment of masonry arch bridges: Case study of Clemente Bridge on Savio river

This research has focused on the study of the behavior and of the collapse of masonry arch bridges. The latest decades have seen an increasing interest in this structural type, that is still present and in use, despite the passage of time and the variation of the transport means. Several strategies have been developed during the time to simulate the response of this type of structures, although even today there is no generally accepted standard one for assessment of masonry arch bridges. The aim of this thesis is to compare the principal analytical and numerical methods existing in literature on case studies, trying to highlight values and weaknesses. The methods taken in exam are mainly three: i) the Thrust Line Analysis Method; ii) the Mechanism Method; iii) the Finite Element Methods. The Thrust Line Analysis Method and the Mechanism Method are analytical methods and derived from two of the fundamental theorems of the Plastic Analysis, while the Finite Element Method is a numerical method, that uses different strategies of discretization to analyze the structure. Every method is applied to the case study through computer-based representations, that allow a friendly-use application of the principles explained. A particular closed-form approach based on an elasto-plastic material model and developed by some Belgian researchers is also studied. To compare the three methods, two different case study have been analyzed: i) a generic masonry arch bridge with a single span; ii) a real masonry arch bridge, the Clemente Bridge, built on Savio River in Cesena. In the analyses performed, all the models are two-dimensional in order to have results comparable between the different methods taken in exam. The different methods have been compared with each other in terms of collapse load and of hinge positions.

Parallelization of the algorithm WHAM with NVIDIA CUDA.

The aim of my thesis is to parallelize the Weighting Histogram Analysis Method (WHAM), which is a popular algorithm used to calculate the Free Energy of a molucular system in Molecular Dynamics simulations. WHAM works in post processing in cooperation with another algorithm called Umbrella Sampling. Umbrella Sampling has the purpose to add a biasing in the potential energy of the system in order to force the system to sample a specific region in the configurational space. Several N independent simulations are performed in order to sample all the region of interest. Subsequently, the WHAM algorithm is used to estimate the original system energy starting from the N atomic trajectories. The parallelization of WHAM has been performed through CUDA, a language that allows to work in GPUs of NVIDIA graphic cards, which have a parallel achitecture. The parallel implementation may sensibly speed up the WHAM execution compared to previous serial CPU imlementations. However, the WHAM CPU code presents some temporal criticalities to very high numbers of interactions. The algorithm has been written in C++ and executed in UNIX systems provided with NVIDIA graphic cards. The results were satisfying obtaining an increase of performances when the model was executed on graphics cards with compute capability greater. Nonetheless, the GPUs used to test the algorithm is quite old and not designated for scientific calculations. It is likely that a further performance increase will be obtained if the algorithm would be executed in clusters of GPU at high level of computational efficiency. The thesis is organized in the following way: I will first describe the mathematical formulation of Umbrella Sampling and WHAM algorithm with their apllications in the study of ionic channels and in Molecular Docking (Chapter 1); then, I will present the CUDA architectures used to implement the model (Chapter 2); and finally, the results obtained on model systems will be presented (Chapter 3).

First doubly polarised photoproduction on 3 He at the photon beam of MAMI

Im Juli 2009 wurde am Mainzer Mikrotron (MAMI) erstmal ein Experiment durchgeführt, bei dem ein polarisiertes 3He Target mit Photonen im Energiebereich von 200 bis 800 MeV untersucht wurde. Das Ziel dieses Experiments war die Überprüfung der Gerasimov-Drell-Hearn Summenregel am Neutron. Die Verwendung der Messdaten welche mit dem polarisierten 3He Target gewonnen wurden, geben - im Vergleich mit den bereits existieren Daten vom Deuteron - aufgrund der Spin-Struktur des 3He einen komplementären und direkteren Zugang zum Neutron. Die Messung des totalen helizitätsabhängigen Photoabsorptions-Wirkungsquerschnitts wurde mittels eines energiemarkierten Strahls von zirkular polarisierten Photonen, welcher auf das longitudinal polarisierte 3He Target trifft, durchgeführt. Als Produktdetektoren kamen der Crystal Ball (4π Raumabdeckung), TAPS (als ”Vorwärtswand”) sowie ein Schwellen-Cherenkov-Detektor (online Veto zur Reduktion von elektromagnetischen Ereignissen) zum Einsatz. Planung und Aufbau der verschiedenen komponenten Teile des 3He Experimentaufbaus war ein entscheidender Teil dieser Dissertation und wird detailliert in der vorliegenden Arbeit beschrieben. Das Detektorsystem als auch die Analyse-Methoden wurden durch die Messung des unpolarisierten, totalen und inklusiven Photoabsoprtions-Wirkungsquerschnitts an flüssigem Wasserstoff getestet. Hierbei zeigten die Ergebnisse eine gute Übereinstimmung mit bereits zuvor publizierten Daten. Vorläufige Ergebnisse des unpolarisierten totalen Photoabsorptions-Wirkungsquerschnitts sowie der helizitätsabhängige Unterschied zwischen Photoabsorptions-Wirkungsquerschnitten an 3He im Vergleich zu verschiedenen theoretischen Modellen werden vorgestellt.

Palaeo wind system reconstruction of the last glacial period over Europe, using high resolution proxy data and model-data-comparison

The atmosphere is a global influence on the movement of heat and humidity between the continents, and thus significantly affects climate variability. Information about atmospheric circulation are of major importance for the understanding of different climatic conditions. Dust deposits from maar lakes and dry maars from the Eifel Volcanic Field (Germany) are therefore used as proxy data for the reconstruction of past aeolian dynamics.rnrnIn this thesis past two sediment cores from the Eifel region are examined: the core SM3 from Lake Schalkenmehren and the core DE3 from the Dehner dry maar. Both cores contain the tephra of the Laacher See eruption, which is dated to 12,900 before present. Taken together the cores cover the last 60,000 years: SM3 the Holocene and DE3 the marine isotope stages MIS-3 and MIS-2, respectively. The frequencies of glacial dust storm events and their paleo wind direction are detected by high resolution grain size and provenance analysis of the lake sediments. Therefore two different methods are applied: geochemical measurements of the sediment using µXRF-scanning and the particle analysis method RADIUS (rapid particle analysis of digital images by ultra-high-resolution scanning of thin sections).rnIt is shown that single dust layers in the lake sediment are characterized by an increased content of aeolian transported carbonate particles. The limestone-bearing Eifel-North-South zone is the most likely source for the carbonate rich aeolian dust in the lake sediments of the Dehner dry maar. The dry maar is located on the western side of the Eifel-North-South zone. Thus, carbonate rich aeolian sediment is most likely to be transported towards the Dehner dry maar within easterly winds. A methodology is developed which limits the detection to the aeolian transported carbonate particles in the sediment, the RADIUS-carbonate module.rnrnIn summary, during the marine isotope stage MIS-3 the storm frequency and the east wind frequency are both increased in comparison to MIS-2. These results leads to the suggestion that atmospheric circulation was affected by more turbulent conditions during MIS-3 in comparison to the more stable atmospheric circulation during the full glacial conditions of MIS-2.rnThe results of the investigations of the dust records are finally evaluated in relation a study of atmospheric general circulation models for a comprehensive interpretation. Here, AGCM experiments (ECHAM3 and ECHAM4) with different prescribed SST patterns are used to develop a synoptic interpretation of long-persisting east wind conditions and of east wind storm events, which are suggested to lead to an enhanced accumulation of sediment being transported by easterly winds to the proxy site of the Dehner dry maar.rnrnThe basic observations made on the proxy record are also illustrated in the 10 m-wind vectors in the different model experiments under glacial conditions with different prescribed sea surface temperature patterns. Furthermore, the analysis of long-persisting east wind conditions in the AGCM data shows a stronger seasonality under glacial conditions: all the different experiments are characterized by an increase of the relative importance of the LEWIC during spring and summer. The different glacial experiments consistently show a shift from a long-lasting high over the Baltic Sea towards the NW, directly above the Scandinavian Ice Sheet, together with contemporary enhanced westerly circulation over the North Atlantic.rnrnThis thesis is a comprehensive analysis of atmospheric circulation patterns during the last glacial period. It has been possible to reconstruct important elements of the glacial paleo climate in Central Europe. While the proxy data from sediment cores lead to a binary signal of the wind direction changes (east versus west wind), a synoptic interpretation using atmospheric circulation models is successful. This shows a possible distribution of high and low pressure areas and thus the direction and strength of wind fields which have the capacity to transport dust. In conclusion, the combination of numerical models, to enhance understanding of processes in the climate system, with proxy data from the environmental record is the key to a comprehensive approach to paleo climatic reconstruction.rn

Development Of New Toolkits For Orbit Determination Codes For Precise Radio Tracking Experiments

This thesis describes the developments of new models and toolkits for the orbit determination codes to support and improve the precise radio tracking experiments of the Cassini-Huygens mission, an interplanetary mission to study the Saturn system. The core of the orbit determination process is the comparison between observed observables and computed observables. Disturbances in either the observed or computed observables degrades the orbit determination process. Chapter 2 describes a detailed study of the numerical errors in the Doppler observables computed by NASA's ODP and MONTE, and ESA's AMFIN. A mathematical model of the numerical noise was developed and successfully validated analyzing against the Doppler observables computed by the ODP and MONTE, with typical relative errors smaller than 10%. The numerical noise proved to be, in general, an important source of noise in the orbit determination process and, in some conditions, it may becomes the dominant noise source. Three different approaches to reduce the numerical noise were proposed. Chapter 3 describes the development of the multiarc library, which allows to perform a multi-arc orbit determination with MONTE. The library was developed during the analysis of the Cassini radio science gravity experiments of the Saturn's satellite Rhea. Chapter 4 presents the estimation of the Rhea's gravity field obtained from a joint multi-arc analysis of Cassini R1 and R4 fly-bys, describing in details the spacecraft dynamical model used, the data selection and calibration procedure, and the analysis method followed. In particular, the approach of estimating the full unconstrained quadrupole gravity field was followed, obtaining a solution statistically not compatible with the condition of hydrostatic equilibrium. The solution proved to be stable and reliable. The normalized moment of inertia is in the range 0.37-0.4 indicating that Rhea's may be almost homogeneous, or at least characterized by a small degree of differentiation.

Numerical studies of colloidal systems

The interplay of hydrodynamic and electrostatic forces is of great importance for the understanding of colloidal dispersions. Theoretical descriptions are often based on the so called standard electrokinetic model. This Mean Field approach combines the Stokes equation for the hydrodynamic flow field, the Poisson equation for electrostatics and a continuity equation describing the evolution of the ion concentration fields. In the first part of this thesis a new lattice method is presented in order to efficiently solve the set of non-linear equations for a charge-stabilized colloidal dispersion in the presence of an external electric field. Within this framework, the research is mainly focused on the calculation of the electrophoretic mobility. Since this transport coefficient is independent of the electric field only for small driving, the algorithm is based upon a linearization of the governing equations. The zeroth order is the well known Poisson-Boltzmann theory and the first order is a coupled set of linear equations. Furthermore, this set of equations is divided into several subproblems. A specialized solver for each subproblem is developed, and various tests and applications are discussed for every particular method. Finally, all solvers are combined in an iterative procedure and applied to several interesting questions, for example, the effect of the screening mechanism on the electrophoretic mobility or the charge dependence of the field-induced dipole moment and ion clouds surrounding a weakly charged sphere. In the second part a quantitative data analysis method is developed for a new experimental approach, known as "Total Internal Reflection Fluorescence Cross-Correlation Spectroscopy" (TIR-FCCS). The TIR-FCCS setup is an optical method using fluorescent colloidal particles to analyze the flow field close to a solid-fluid interface. The interpretation of the experimental results requires a theoretical model, which is usually the solution of a convection-diffusion equation. Since an analytic solution is not available due to the form of the flow field and the boundary conditions, an alternative numerical approach is presented. It is based on stochastic methods, i. e. a combination of a Brownian Dynamics algorithm and Monte Carlo techniques. Finally, experimental measurements for a hydrophilic surface are analyzed using this new numerical approach.

Nanopartikel und Nanokapseln als potentielle Wirkstofftransportsysteme : zelluläre Aufnahme in Leukozyten in peripherem Vollblut und in Zellkultur

Nanopartikuläre Wirkstofftransportsysteme besitzen ein großes Potential für therapeutische Anwendungen. In der vorliegenden Arbeit wurden verschiedene grundlegende Aspekte, die für das erweiterte biologische Verständnis und die Entwicklung weiterer zielgerichteter Strategien zur Pharmakotherapie mit Nanopartikeln und –kapseln notwendig sind, näher untersucht. Experimente zur zellulären Aufnahmefähigkeit (in vitro und ex vivo) wurden mit verschiedenen Nanopartikeln und –kapseln aus diversen Monomeren und biokompatiblen Makromolekülen in immortalisierten Zellkulturlinien, humanen mesenchymalen Stammzellen und Leukozyten durchgeführt und durchflusszytometrisch sowie mittels konfokaler Laser-Raster-Mikroskopie analysiert. Die Einflüsse der Oberflächenfunktionalisierungen der nanopartikulären Systeme, deren toxikologische Effekte sowie der Einfluss von adsorbiertem bovinem Serumalbumin auf funktionalisierten Polystyrol-Nanopartikeln wurden in Bezug auf die zelluläre Aufnahme untersucht.Um die multiplen Wechselwirkungen der Nanopartikel mit Bestandteilen des humanen peripheren Vollblutes zu untersuchen, wurde erfolgreich ein durchflusszytometrisches Analyseverfahren in antikoaguliertem peripherem Vollblut (ex vivo) entwickelt. Es konnte nachgewiesen werden, dass der Einfluss von Calcium-komplexierenden Antikoagulanzien zu einer Verringerung und nicht Li-Heparin zu einer Verstärkung der zellulären Aufnahme von funktionalisierten Polystyrol-Nanopartikeln in diversen Leukozyten führt.Für Folsäure-gekoppelte Hydroxyethylstärke-Nanokapseln (Synthese Frau Dr. Grit Baier) konnte ein größenabhängiger selektiver, Folatrezeptor α vermittelter, zellulärer Aufnahmeweg in HeLa-Zellen nachgewiesen werden.Hydrolysierbare, nicht zytotoxische Polyester-Nanopartikel aus Poly(5,6-Benzo-2-methylen-1,3-dioxepan) (Synthese Herr Dr. Jörg Max Siebert) mit eingebettetem Paclitaxel zeigten in HeLa-Zellen eine vergleichbare pharmakologische Wirkung wie kommerziell erhältliche Paclitaxel-Formulierungen.Die in dieser Arbeit eingesetzten Nanopartikel und Nanokapseln besitzen ein vielfältiges Potential als Wirkstofftransportsysteme. Es zeigte sich, dass Unterschiede bei der Größe, der Größenverteilung, des Polymers sowie der Oberflächenfunktionalisierung der Nanopartikel bedeutende Unterschiede der Zellaufnahme in diversen Zellkulturlinien (in vitro) und Leukozyten in peripherem Vollblut (ex vivo) zur Folge haben.