Synthesis and characterization of metal-chalcogenide MQ 2-Nanoparticles (M = Mo, W, Zr; Q = S, O)

Here, we present the adaptation and optimization of (i) the solvothermal and (ii) the metal-organic chemical vapor deposition (MOCVD) approach as simple methods for the high-yield synthesis of MQ2 (M=Mo, W, Zr; Q = O, S) nanoparticles. Extensive characterization was carried out using X-ray diffraction (XRD), scanning and transmission electron micros¬copy (SEM/TEM) combined with energy dispersive X-ray analysis (EDXA), Raman spectroscopy, thermal analyses (DTA/TG), small angle X-ray scattering (SAXS) and BET measurements. After a general introduction to the state of the art, a simple route to nanostructured MoS2 based on the decomposition of the cluster-based precursor (NH4)2Mo3S13∙xH2O under solvothermal conditions (toluene, 653 K) is presented. Solvothermal decomposition results in nanostructured material that is distinct from the material obtained by decomposition of the same precursor in sealed quartz tubes at the same temperature. When carried out in the presence of the surfactant cetyltrimethyl¬ammonium bromide (CTAB), the decomposition product exhibits highly disordered MoS2 lamellae with high surface areas. The synthesis of WS2 onion-like nanoparticles by means of a single-step MOCVD process is discussed. Furthermore, the results of the successful transfer of the two-step MO¬CVD based synthesis of MoQ2 nanoparticles (Q = S, Se), comprising the formation of amorphous precursor particles and followed by the formation of fullerene-like particles in a subsequent annealing step to the W-S system, are presented. Based on a study of the temperature dependence of the reactions a set of conditions for the formation of onion-like structures in a one-step reaction could be derived. The MOCVD approach allows a selective synthesis of open and filled fullerene-like chalcogenide nanoparticles. An in situ heating stage transmission electron microscopy (TEM) study was employed to comparatively investigate the growth mechanism of MoS2 and WS2 nanoparticles obtained from MOCVD upon annealing. Round, mainly amorphous particles in the pristine sample trans¬form to hollow onion-like particles upon annealing. A significant difference between both compounds could be demonstrated in their crystallization conduct. Finally, the results of the in situ hea¬ting experiments are compared to those obtained from an ex situ annealing process under Ar. Eventually, a low temperature synthesis of monodisperse ZrO2 nanoparticles with diameters of ~ 8 nm is introduced. Whereas the solvent could be omitted, the synthesis in an autoclave is crucial for gaining nano-sized (n) ZrO2 by thermal decomposition of Zr(C2O4)2. The n-ZrO2 particles exhibits high specific surface areas (up to 385 m2/g) which make them promising candidates as catalysts and catalyst supports. Co-existence of m- and t-ZrO2 nano-particles of 6-9 nm in diameter, i.e. above the critical particle size of 6 nm, demonstrates that the particle size is not the only factor for stabilization of the t-ZrO2 modification at room temperature. In conclusion, synthesis within an autoclave (with and without solvent) and the MOCVD process could be successfully adapted to the synthesis of MoS2, WS2 and ZrO2 nanoparticles. A comparative in situ heating stage TEM study elucidated the growth mechanism of MoS2 and WS2 fullerene-like particles. As the general processes are similar, a transfer of this synthesis approach to other layered transition metal chalcogenide systems is to be expected. Application of the obtained nanomaterials as lubricants (MoS2, WS2) or as dental filling materials (ZrO2) is currently under investigation.

Co-simulazione e co-progetto non lineare/elettromagnetico di sistemi wireless non convenzionali

L’attività di ricerca contenuta in questa tesi si è concentrata nello sviluppo e nell’implementazione di tecniche per la co-simulazione e il co-progetto non lineare/elettromagnetico di sistemi wireless non convenzionali. Questo lavoro presenta un metodo rigoroso per considerare le interazioni tra due sistemi posti sia in condizioni di campo vicino che in condizioni di campo lontano. In sostanza, gli effetti del sistema trasmittente sono rappresentati da un generatore equivalente di Norton posto in parallelo all’antenna del sistema ricevente, calcolato per mezzo del teorema di reciprocità e del teorema di equivalenza. La correttezza del metodo è stata verificata per mezzo di simulazioni e misure, concordi tra loro. La stessa teoria, ampliata con l’introduzione degli effetti di scattering, è stata usata per valutare una condizione analoga, dove l’elemento trasmittente coincide con quello ricevente (DIE) contenuto all’interno di una struttura metallica (package). I risultati sono stati confrontati con i medesimi ottenibili tramite tecniche FEM e FDTD/FIT, che richiedono tempi di simulazione maggiori di un ordine di grandezza. Grazie ai metodi di co-simulazione non lineari/EM sopra esposti, è stato progettato e verificato un sistema di localizzazione e identificazione di oggetti taggati posti in ambiente indoor. Questo è stato ottenuto dotando il sistema di lettura, denominato RID (Remotely Identify and Detect), di funzioni di scansione angolare e della tecnica di RADAR mono-pulse. Il sistema sperimentale, creato con dispositivi low cost, opera a 2.5 GHz ed ha le dimensioni paragonabili ad un normale PDA. E’ stato sperimentata la capacità del RID di localizzare, in scenari indoor, oggetti statici e in movimento.

Synthesis and evaluation of 18-F-radiopharmaceuticals within the serotonergic receptor system for molecular imaging

Molecular imaging technologies as Positron Emission Tomography (PET) are playing a key role in drug discovery, development and delivery due to the possibility to quantify e.g. the binding potential in vivo, non-invasively and repetitively. In this context, it provides a significant advance in the understanding of many CNS disorders and conditions. The serotonergic receptor system is involved in a number of important physiological processes and diseases such as depression, schizophrenia, Alzheimer’s disease, sleep or sexual behaviour. Especially, the 5-HT2A and the 5-HT1A receptor subtypes are in the focus of fundamental and clinical research due to the fact that many psychotic drugs interact with these neuronal transmembrane receptors. This work describes the successful development, as well as in vitro and in vivo evaluation of 5-HT2A and 5-HT1A selective antagonistic PET-radiotracers. The major achievements obtained in this thesis are: 1. the development and in vitro evaluation of several 5-HT2A antagonistic compounds, namely MH.MZ (Ki = 9.0 nM), (R)-MH.MZ (Ki = 0.72 nM) and MA-1 (Ki = 3.0 nM). 2. the 18F-labeling procedure of these compounds and their optimization, whereby radiochemical yields > 35 % in high specific activities (> 15 GBq/µmol) could be observed. Synthesis time inclusive secondary synthon synthesis, the radioactive labeling procedure, separation and final formulation took no longer than 120 min and provided the tracer in high radiochemical purity. 3. the in vivo µPET evaluation of [18F]MH.MZ and (R)-[18F]MH.MZ resulting in promising imaging agents of the 5-HT2A receptor status; from which (R)-[18F]MH.MZ seems to be the most promising ligand. 4. the determination of the influence of P-gp on the brain biodistribution of [18F]MH.MZ showing a strong P-gp dependency but no regional alteration. 5. the four-step radiosynthesis and evaluation of [18F]MDL 100907 resulting in another high affine tracer, which is, however, limited due to its low radiochemical yield. 6. the development and evaluation of 3 novel possible 5-HT2A imaging agents combining structural elements of altanserin, MDL 100907 and SR 46349B demonstrating different binding modes of these compounds. 7. the development, the labeling and in vitro evaluation of the novel 5-HT1A antagonistic tracer [18F]AH1.MZ (Ki = 4.2 nM).

Spectroscopic studies on Cyclodextrin and Metal Organic Framework based potential nanovectors for delivery of Anticancer and Antiviral drugs

The aim of this work is to contribute to the development of new multifunctional nanocarriers for improved encapsulation and delivery of anticancer and antiviral drugs. The work focused on water soluble and biocompatible oligosaccharides, the cyclodextrins (CyDs), and a new family of nanostructured, biodegradable carrier materials made of porous metal-organic frameworks (nanoMOFs). The drugs of choice were the anticancer doxorubicin (DOX), azidothymidine (AZT) and its phosphate derivatives and artemisinin (ART). DOX possesses a pharmacological drawback due to its self-aggregation tendency in water. The non covalent binding of DOX to a series of CyD derivatives, such as g-CyD, an epichlorohydrin crosslinked b-CyD polymer (pb-CyD) and a citric acid crosslinked g-CyD polymer (pg-CyD) was studied by UV visible absorption, circular dichroism and fluorescence. Multivariate global analysis of multiwavelength data from spectroscopic titrations allowed identification and characterization of the stable complexes. pg-CyD proved to be the best carrier showing both high association constants and ability to monomerize DOX. AZT is an important antiretroviral drug. The active form is AZT-triphosphate (AZT-TP), formed in metabolic paths of low efficiency. Direct administration of AZT-TP is limited by its poor stability in biological media. So the development of suitable carriers is highly important. In this context we studied the binding of some phosphorilated derivatives to nanoMOFs by spectroscopic methods. The results obtained with iron(III)-trimesate nanoMOFs allowed to prove that the binding of these drugs mainly occurs by strong iono-covalent bonds to iron(III) centers. On the basis of these and other results obtained in partner laboratories, it was possible to propose this highly versatile and “green” carrier system for delivery of phosphorylated nucleoside analogues. The interaction of DOX with nanoMOFs was also studied. Finally the binding of the antimalarial drug, artemisinin (ART) with two cyclodextrin-based carriers,the pb-CyD and a light responsive bis(b-CyD) host, was also studied.

Nanoscopic studies of conjugated polymer blends by (electric) scanning probe microscopy

Conjugated polymers and conjugated polymer blends have attracted great interest due to their potential applications in biosensors and organic electronics. The sub-100 nm morphology of these materials is known to heavily influence their electromechanical properties and the performance of devices they are part of. Electromechanical properties include charge injection, transport, recombination, and trapping, the phase behavior and the mechanical robustness of polymers and blends. Electrical scanning probe microscopy techniques are ideal tools to measure simultaneously electric (conductivity and surface potential) and dielectric (dielectric constant) properties, surface morphology, and mechanical properties of thin films of conjugated polymers and their blends.rnIn this thesis, I first present a combined topography, Kelvin probe force microscopy (KPFM), and scanning conductive torsion mode microscopy (SCTMM) study on a gold/polystyrene model system. This system is a mimic for conjugated polymer blends where conductive domains (gold nanoparticles) are embedded in a non-conductive matrix (polystyrene film), like for polypyrrole:polystyrene sulfonate (PPy:PSS), and poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS). I controlled the nanoscale morphology of the model by varying the distribution of gold nanoparticles in the polystyrene films. I studied the influence of different morphologies on the surface potential measured by KPFM and on the conductivity measured by SCTMM. By the knowledge I gained from analyzing the data of the model system I was able to predict the nanostructure of a homemade PPy:PSS blend.rnThe morphologic, electric, and dielectric properties of water based conjugated polymer blends, e.g. PPy:PSS or PEDOT:PSS, are known to be influenced by their water content. These properties also influence the macroscopic performance when the polymer blends are employed in a device. In the second part I therefore present an in situ humidity-dependence study on PPy:PSS films spin-coated and drop-coated on hydrophobic highly ordered pyrolytic graphite substrates by KPFM. I additionally used a particular KPFM mode that detects the second harmonic electrostatic force. With this, I obtained images of dielectric constants of samples. Upon increasing relative humidity, the surface morphology and composition of the films changed. I also observed that relative humidity affected thermally unannealed and annealed PPy:PSS films differently. rnThe conductivity of a conjugated polymer may change once it is embedded in a non-conductive matrix, like for PPy embedded in PSS. To measure the conductivity of single conjugated polymer particles, in the third part, I present a direct method based on microscopic four-point probes. I started with metal core-shell and metal bulk particles as models, and measured their conductivities. The study could be extended to measure conductivity of single PPy particles (core-shell and bulk) with a diameter of a few micrometers.

Analysis of an innovative slim floor composite beam conformed by a custom GFRP pultruded profile and reinforced concrete.

GFRP pultruded profiles have shown to be structural profiles with great stiffness, strenght and very low specific weight, making it a great candidate for the rehabilitation of damaged strucutres. To further enhance the strucutral mechanism of these type of beams, the Slimflor composite structural system has lead as basis for this analysis; by replacing the steel beam with a GFRP pultruded profile. To further increase its composite action, a continuous shear connector has been set as part of the beam cross section as well as its needed reinforcement and fire protection.

Development of an X-ray spectrometric system and feasibility tests of Silicon Drift Detector for medical and space applications

The thesis work concerns X-ray spectrometry for both medical and space applications and is divided into two sections. The first section addresses an X-ray spectrometric system designed to study radiological beams and is devoted to the optimization of diagnostic procedures in medicine. A parametric semi-empirical model capable of efficiently reconstructing diagnostic X-ray spectra in 'middle power' computers was developed and tested. In addition, different silicon diode detectors were tested as real-time detectors in order to provide a real-time evaluation of the spectrum during diagnostic procedures. This project contributes to the field by presenting an improved simulation of a realistic X-ray beam emerging from a common X-ray tube with a complete and detailed spectrum that lends itself to further studies of added filtration, thus providing an optimized beam for different diagnostic applications in medicine. The second section describes the preliminary tests that have been carried out on the first version of an Application Specific Integrated Circuit (ASIC), integrated with large area position-sensitive Silicon Drift Detector (SDD) to be used on board future space missions. This technology has been developed for the ESA project: LOFT (Large Observatory for X-ray Timing), a new medium-class space mission that the European Space Agency has been assessing since February of 2011. The LOFT project was proposed as part of the Cosmic Vision Program (2015-2025).

Laser driven proton acceleration and beam shaping

In the race to obtain protons with higher energies, using more compact systems at the same time, laser-driven plasma accelerators are becoming an interesting possibility. But for now, only beams with extremely broad energy spectra and high divergence have been produced. The driving line of this PhD thesis was the study and design of a compact system to extract a high quality beam out of the initial bunch of protons produced by the interaction of a laser pulse with a thin solid target, using experimentally reliable technologies in order to be able to test such a system as soon as possible. In this thesis, different transport lines are analyzed. The first is based on a high field pulsed solenoid, some collimators and, for perfect filtering and post-acceleration, a high field high frequency compact linear accelerator, originally designed to accelerate a 30 MeV beam extracted from a cyclotron. The second one is based on a quadruplet of permanent magnetic quadrupoles: thanks to its greater simplicity and reliability, it has great interest for experiments, but the effectiveness is lower than the one based on the solenoid; in fact, the final beam intensity drops by an order of magnitude. An additional sensible decrease in intensity is verified in the third case, where the energy selection is achieved using a chicane, because of its very low efficiency for off-axis protons. The proposed schemes have all been analyzed with 3D simulations and all the significant results are presented. Future experimental work based on the outcome of this thesis can be planned and is being discussed now.

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.

Transport properties of YBa 2 Cu 3 O 7, PrBa 2 Cu 3 O 7-superlattices

The understanding of the coupling between superconducting YBa2Cu3O7 (YBCO) layers decoupled by non superconducting PrBa2Cu3O7 (PBCO) layers in c-axis oriented superlattices was the aim of this thesis. For this purpose two conceptually different kind of transport experiments have been performed. rnrnIn the first type of transport experiments the current is flowing parallel to the layers. Here the coupling is probed indirectly using magnetic vortex lines, which are penetrating the superlattice. Movement of the vortex segments in neighbouring YBCO layers is more or less coherent depending on the thickness of both the superconducting and non superconducting layers. This in-plane transport was measured either by sending an external current through bridges patterned in the superlattice or by an induced internal current. rnThe vortex-creep activation energy U was determined by analysis of the in-plane resistive transition in an external magnetic field B oriented along the c-axis. The activation energies for two series of superlattices were investigated. In one series the thickness of the YBCO layers was constant (nY=4 unit cells) and the number of the PBCO unit cells was varied, while in the other the number of PBCO layers was constant (nP=4) and nY varied. The correlation length of the vortex system was determined to be 80 nm along the c-axis direction. It was found that even a single PBCO unit cell in a superlattice effectively cuts the flux lines into shorter weakly coupled segments, and the coupling of the vortex systems in neighbouring layers is negligible already for a thickness of four unit cells of the PBCO layers. A characteristic variation of the activation energy for the two series of superlattices was found, where U0 is proportional to the YBCO thickness. A change in the variation of U0 with the current I in the specimen was observed, which can be explained in terms of a crossover in the vortex creep process, generated by the transport current. At low I values the dislocations mediated (plastic) vortex creep leads to thermally assisted flux-flow behaviour, whereas at high current the dc transport measurements are dominated by elastic (collective) creep.rnThe analysis of standard dc magnetization relaxation data obtained for a series superlattices revealed the occurrence of a crossover from elastic (collective) vortex creep at low temperature to plastic vortex creep at high T. The crossover is generated by the T dependent macroscopic currents induced in the sample. The existence of this creep crossover suggests that, compared with the well known Maley technique, the use of the normalized vortex creep activation energy is a better solution for the determination of vortex creep parameters.rnrnThe second type of transport experiments was to measure directly a possible Josephson coupling between superconducting CuO2 double planes in the superlattices by investigation of the transport properties perpendicular to the superconducting planes. Here three different experiments have been performed. The first one was to pattern mesa structures photolithographically as in previous works. The second used three-dimensional nanostructures cut by a focused ion beam. For the these two experiments insufficient patterning capabilities prevented an observation of the Josephson effect in the current voltage curves. rnA third experiment used a-axis and (110) oriented YBCO films, where in-plane patterning can in principle be sufficient to measure transport perpendicular to the superconducting planes. Therefore the deposition of films with this unusual growth orientation was optimized and investigated. The structural and microstructural evolution of c-axis to a-axis orientation was monitored using x-ray diffraction, scanning electron microscopy and magnetization measurements. Films with full a-axis alignment parallel to the substrate normal could be achieved on (100)SrTiO3. Due to the symmetry of the substrate the c-axis direction in-plane is twofold. Transferring the deposition conditions to films grown on (110)SrTiO3 allowed the growth of (110) oriented YBCO films with a unique in-plane c-axis orientation. While these films were of high quality by crystallographic and macroscopic visual inspection, electron microscopy revealed a coherent crack pattern on a nanoscale. Therefore the actual current path in the sample was not determined by the macroscopic patterning which prohibited investigations of the in-plane anisotropy in this case.rn

Strategie formulative per la veicolazione nasale di farmaci

Microparticelle a base di complessi polielettrolitici di Chitosano/Pectina per il rilascio nasale di Tacrina cloridrato. Lo scopo di questo studio è stata la ricerca di nuove formulazioni solide per la somministrazione nasale di Tacrina cloridrato allo scopo di ridurre l’eccessivo effetto di primo passaggio epatico ed aumentarne la biodisponibilità a livello del Sistema Nervoso Centrale. La Tacrina è stata incapsulata in microparticelle mucoadesive a base di complessi elettrolitici di chitosano e pectina. Le microparticelle sono state preparate mediante due diversi approcci tecnologici (spray-drying e spray-drying/liofilizzazione) e analizzate in termini di caratteristiche dimensionali, morfologiche e chimico-fisiche. Nanoparticelle di Chitosano reticolate con Sodio Cromoglicato per il trattamento della rinite allergica. Il Sodio Cromoglicato è uno dei farmaci utilizzati per il trattamento della rinite allergica. Come noto, la clearance mucociliare provoca una rapida rimozione dei farmaci in soluzione dalla cavità nasale, aumentando così il numero di somministrazioni giornaliere e, di conseguenza, riducendo la compliance del paziente. Per ovviare a tale problema, si è pensato di includere il sodio cromoglicato in nanoparticelle di chitosano, un polimero capace di aderire alla mucosa nasale, prolungare il contatto della formulazione con il sito di applicazione e ridurre il numero di somministrazioni giornaliere. Le nanoparticelle ottenute sono state caratterizzate in termini di dimensioni, resa, efficienza di incapsulazione e caricamento del farmaco, potenziale zeta e caratteristiche mucoadesive. Analisi quantitativa di Budesonide amorfa tramite calorimetria a scansione differenziale. È stato sviluppato un nuovo metodo quantitativo allo stato solido basato sulla Calorimetria a Scansione Differenziale (DSC) in grado di quantificare in modo selettivo e accurato la quantità di Budesonide amorfa presente in una miscela solida. Durante lo sviluppo del metodo sono stati affrontati problemi relativi alla convalida di metodi analitici su campioni solidi quali la miscelazione di polveri solide per la preparazione di miscele standard e il calcolo della precisione.

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

The new Beam Halo Monitor for the CMS experiment at the LHC

In the context of increasing beam energy and luminosity of the LHC accelerator at CERN, it will be important to accurately measure the Machine Induced Background. A new monitoring system will be installed in the CMS cavern for measuring the beam background at high radius. This detector, called the Beam Halo Monitor, will provide an online, bunch-by-bunch measurement of background induced by beam halo interactions, separately for each beam. The detector is composed of synthetic quartz Cherenkov radiators, coupled to fast UV sensitive photomultiplier tubes. The directional and fast response of the system allows the discrimination of the background particles from the dominant flux in the cavern induced by pp collision debris, produced within the 25 ns bunch spacing. The readout electronics of this detector will make use of many components developed for the upgrade of the CMS Hadron Calorimeter electronics, with a dedicated firmware and readout adapted to the beam monitoring requirements. The PMT signal will be digitized by a charge integrating ASIC, providing both the signal rise time and the charge integrated over one bunch crossing. The backend electronics will record bunch-by-bunch histograms, which will be published to CMS and the LHC using the newly designed CMS beam instrumentation specific DAQ. A calibration and monitoring system has been designed to generate triggered pulses of UV light to monitor the efficiency of the system. The experimental results validating the design of the detector, the calibration system and the electronics will be presented.

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.

Bioverkapselung lebender Bakterien (Escherichia coli) mit Poly-(Silicat) nach Transformation mit dem Silicatein-alpha-Gen

Die Bioverkapselung ist eine faszinierende Methode, um biologische Materialien einschließlich Zellen in Siliziumdioxid, Metalloxiden oder hybriden Sol-Gel-Polymeren zu immobilisieren. Bisher wurde nur die Sol-Gel-Vorläufertechnologie genutzt, um Bakterien- oder Hefezellen in Siliziumdioxid zu immobilisieren. Hierfür wurden verschiedene Reagenzien als wässrige Vorläufer getestet, um poly(Silicate) auf Biomolekülen (Bhatia et al., 2000) oder Zellen (Liu und Chen 1999; Coradin und Livage, 2007) zu bilden. Einer der erfolgreichsten bisherigen Methoden verwendet eine Mischung aus Silicaten und kolloidalem Silica. Diese initialen Vorläufer werden durch die Zugabe von Salzsäure neutralisiert, was die Gelbildung fortschreiten lässt und die Verkapselung von Bakterien in einem Silica-Netzwerk zur Folge hat (Nassif et al., 2003). Mit der Entdeckung von Silicatein, einem Enzym, das aus Demospongien isoliert wurde und die Bildung von poly(Silicat) katalysiert, wurde es möglich, poly(Silicat) unter physiologischen Bedingungen zu synthetisieren. Silicatein wurde rekombinant in E. coli hergestellt und ist in der Lage, bei Raumtemperatur, neutralem pH-Wert und in wässrigen Puffersystemen aus Siliziumalkoxiden poly(Silicat) zu bilden (Krasko et al., 2000; Müller et al., 2007b; Zhou et al., 1999). In vivo katalysiert Silicatein die Synthese der Silicathülle der Schwamm-Spiculae (Skelettelemente; Müller et al., 2005b; Müller et al., 2007a; Müller et al., 2007b; Schröder et al., 2007a). Dieses Biosilica wurde in Form von Silica-Nanospheren mit Durchmessern zwischen 100 nm und 250 nm organisiert vorgefunden (Pisera 2003; Tahir et al., 2005). Mit dieser Arbeit konnte gezeigt werden, dass Escherichia coli erfolgreich mit dem Silicatein-Gen transformiert werden kann. Das Level der Proteinexpression kann in Anwesenheit von Isopropyl-β-D-thiogalaktopyranosid (IPTG) effizient erhöht werden, indem man die Bakterienzellen gleichzeitig mit Kieselsäure inkubiert. Dieser Effekt konnte sowohl auf Ebene der Synthese des rekombinanten Proteins durch Western Blot als auch durch Immunfluoreszenzmikroskopie nachgewiesen werden. Das heterolog produzierte Silicatein besitzt enzymatische Aktivität und kann die Polymerisation von Kieselsäure katalysieren. Dies konnte sowohl durch Färbung mit Rhodamin123, als auch durch Reaktion der nicht polymerisierten, freien Kieselsäure mit dem ß-Silicomolybdato-Farbsystem (Silicomolybdänblau) nachgewiesen werden. Elektronenmikroskopische Untersuchungen zeigten, dass nur die silicateinexprimierenden Bakterien während des Wachstums in Anwesenheit von Kieselsäure eine viskose Hülle um Zelle herum bilden. Ebenfalls konnte gezeigt werden, dass Silicatein-α aus Suberites domuncula nach Transformation in E. coli an die Zelloberfläche dieser Zellen transportiert wurde und dort seine enzymatische Funktion beibehielt. Die Silicathülle wurde mittels Raster-Elektronenmikroskopie (REM) analysiert. Die Bakterien, die Silicatein exprimierten und poly(Silicat) an ihrer Oberfläche synthetisierten, zeigten die gleichen Wachstumsraten wie die Bakterien, die das Gen nicht enthielten. Schlussfolgernd lässt sich sagen, dass die silicateinvermittelte Verkapselung von Bakterien mit poly(Silicat) die Bandbreite der Anwendung von Bakterien für die Produktion von rekombinanten Proteinen verbessern, erweitern und optimieren könnte.