Development and evaluation of a 44 Ti, 44 Sc radionuclide generator and labeling of biomolecules with 44 Sc and 68 Ga for PET imaging

Non-invasive molecular-imaging technologies are playing a key role in drug discovery, development and delivery. Positron Emission Tomography (PET) is such a molecular imaging technology and a powerful tool for the observation of various deceases in vivo. However, it is limited by the availability of vectors with high selectivity to the target and radionuclides with a physical half-life which matches the biological half-life of the observed process. The 68Ge/68Ga radionuclide generator makes the PET-nuclide anywhere available without an on-site cyclotron. Besides the perfect availability 68Ga shows well suited nuclide properties for PET, but it has to be co-ordinated by a chelator to introduce it in a radiopharmaceuticals.rnHowever, the physical half-life of 68Ga (67.7 min) might limit the spectrum of clinical applications of 68Ga-labelled radiodiagnostics. Furthermore, 68Ga-labelled analogues of endoradiotherapeuticals of longer biological half-live such as 90Y- or 177Lu-labeled peptides and proteins cannot be used to determine individual radiation dosimetry directly. rnThus, radionuclide generator systems providing positron emitting daughters of extended physical half-life are of renewed interest. In this context, generator-derived positron emitters with longer physical half-life are needed, such as 72As (T½ = 26 h) from the 72Se/72As generator, or 44Sc (T½ = 3.97 h) from the 44Ti/44Sc generator.rnIn this thesis the implementation of radioactive gallium-68 and scandium-44 for molecular imaging and nuclear medical diagnosis, beginning with chemical separation and purification of 44Ti as a radionuclide mother, investigation of pilot generators with different elution mode, building a prototype generator, development and investigation of post-processing of the generator eluate, its concentration and further purification, the labeling chemistry under different conditions, in vitro and in vivo studies of labeled compounds and, finally, in vivo imaging experiments are described.

A multi-objective genetic algorithm optimisation using variable speed pumps in water distribution systems

Due to its practical importance and inherent complexity, the optimisation of distribution networks for supplying drinking water has been the subject of extensive study for the past 30 years. The optimization is governed by sizing the pipes in the water distribution network (WDN) and / or optimises specific parts of the network such as pumps, tanks etc. or try to analyse and optimise the reliability of a WDN. In this thesis, the author has analysed two different WDNs (Anytown City and Cabrera city networks), trying to solve and optimise a multi-objective optimisation problem (MOOP). The main two objectives in both cases were the minimisation of Energy Cost (€) or Energy consumption (kWh), along with the total Number of pump switches (TNps) during a day. For this purpose, a decision support system generator for Multi-objective optimisation used. Its name is GANetXL and has been developed by the Center of Water System in the University of Exeter. GANetXL, works by calling the EPANET hydraulic solver, each time a hydraulic analysis has been fulfilled. The main algorithm used, was a second-generation algorithm for multi-objective optimisation called NSGA_II that gave us the Pareto fronts of each configuration. The first experiment that has been carried out was the network of Anytown city. It is a big network with a pump station of four fixed speed parallel pumps that are boosting the water dynamics. The main intervention was to change these pumps to new Variable speed driven pumps (VSDPs), by installing inverters capable to diverse their velocity during the day. Hence, it’s been achieved great Energy and cost savings along with minimisation in the number of pump switches. The results of the research are thoroughly illustrated in chapter 7, with comments and a variety of graphs and different configurations. The second experiment was about the network of Cabrera city. The smaller WDN had a unique FS pump in the system. The problem was the same as far as the optimisation process was concerned, thus, the minimisation of the energy consumption and in parallel the minimisation of TNps. The same optimisation tool has been used (GANetXL).The main scope was to carry out several and different experiments regarding a vast variety of configurations, using different pump (but this time keeping the FS mode), different tank levels, different pipe diameters and different emitters coefficient. All these different modes came up with a large number of results that were compared in the chapter 8. Concluding, it should be said that the optimisation of WDNs is a very interested field that has a vast space of options to deal with. This includes a large number of algorithms to choose from, different techniques and configurations to be made and different support system generators. The researcher has to be ready to “roam” between these choices, till a satisfactory result will convince him/her that has reached a good optimisation point.

Inversion of low frequency seismo-volcanic events

The inversion of seismo-volcanic events is performed to retrieve the source geometry and to determine volumetric budgets of the source. Such observations have shown to be an important tool for the seismological monitoring of volcanoes. We developed a novel technique for the non-linear constrained inversion of low frequency seismo-volcanic events. Unconstrained linear inversion methods work well when a dense network of broadband seismometers is available. We propose a new constrained inversion technique, which has shown to be efficient also in a reduced network configuration and a low signal-noise ratio. The waveform inversion is performed in the frequency domain, constraining the source mechanism during the event to vary only in its magnitude. The eigenvectors orientation and the eigenvalue ratio are kept constant. This significantly reduces the number of parameters to invert, making the procedure more stable. The method has been tested over a synthetic dataset, reproducing realistic very-long-period (VLP) signals of Stromboli volcano. The information obtained by performing the synthetic tests is used to assess the reliability of the results obtained on a VLP dataset recorded on Stromboli volcano and on a low frequency events recorded at Vesuvius volcano.

High precision swept volume approximation with conservative error bounds

In technical design processes in the automotive industry, digital prototypes rapidly gain importance, because they allow for a detection of design errors in early development stages. The technical design process includes the computation of swept volumes for maintainability analysis and clearance checks. The swept volume is very useful, for example, to identify problem areas where a safety distance might not be kept. With the explicit construction of the swept volume an engineer gets evidence on how the shape of components that come too close have to be modified.rnIn this thesis a concept for the approximation of the outer boundary of a swept volume is developed. For safety reasons, it is essential that the approximation is conservative, i.e., that the swept volume is completely enclosed by the approximation. On the other hand, one wishes to approximate the swept volume as precisely as possible. In this work, we will show, that the one-sided Hausdorff distance is the adequate measure for the error of the approximation, when the intended usage is clearance checks, continuous collision detection and maintainability analysis in CAD. We present two implementations that apply the concept and generate a manifold triangle mesh that approximates the outer boundary of a swept volume. Both algorithms are two-phased: a sweeping phase which generates a conservative voxelization of the swept volume, and the actual mesh generation which is based on restricted Delaunay refinement. This approach ensures a high precision of the approximation while respecting conservativeness.rnThe benchmarks for our test are amongst others real world scenarios that come from the automotive industry.rnFurther, we introduce a method to relate parts of an already computed swept volume boundary to those triangles of the generator, that come closest during the sweep. We use this to verify as well as to colorize meshes resulting from our implementations.

Monodromy calculations for some differential equations

In vielen Teilgebieten der Mathematik ist es w"{u}nschenswert, die Monodromiegruppe einer homogenen linearen Differenzialgleichung zu verstehen. Es sind nur wenige analytische Methoden zur Berechnung dieser Gruppe bekannt, daher entwickeln wir im ersten Teil dieser Arbeit eine numerische Methode zur Approximation ihrer Erzeuger.rnIm zweiten Abschnitt fassen wir die Grundlagen der Theorie der Uniformisierung Riemannscher Fl"achen und die der arithmetischen Fuchsschen Gruppen zusammen. Auss erdem erkl"aren wir, wie unsere numerische Methode bei der Bestimmung von uniformisierenden Differenzialgleichungen dienlich sein kann. F"ur arithmetische Fuchssche Gruppen mit zwei Erzeugern erhalten wir lokale Daten und freie Parameter von Lam'{e} Gleichungen, welche die zugeh"origen Riemannschen Fl"achen uniformisieren. rnIm dritten Teil geben wir einen kurzen Abriss zur homologischen Spiegelsymmetrie und f"uhren die $widehat{Gamma}$-Klasse ein. Wir erkl"aren wie diese genutzt werden kann, um eine Hodge-theoretische Version der Spiegelsymmetrie f"ur torische Varit"aten zu beweisen. Daraus gewinnen wir Vermutungen "uber die Monodromiegruppe $M$ von Picard-Fuchs Gleichungen von gewissen Familien $f:mathcal{X}rightarrow bbp^1$ von $n$-dimensionalen Calabi-Yau Variet"aten. Diese besagen erstens, dass bez"uglich einer nat"urlichen Basis die Monodromiematrizen in $M$ Eintr"age aus dem K"orper $bbq(zeta(2j+1)/(2 pi i)^{2j+1},j=1,ldots,lfloor (n-1)/2 rfloor)$ haben. Und zweitens, dass sich topologische Invarianten des Spiegelpartners einer generischen Faser von $f:mathcal{X}rightarrow bbp^1$ aus einem speziellen Element von $M$ rekonstruieren lassen. Schliess lich benutzen wir die im ersten Teil entwickelten Methoden zur Verifizierung dieser Vermutungen, vornehmlich in Hinblick auf Dimension drei. Dar"uber hinaus erstellen wir eine Liste von Kandidaten topologischer Invarianten von vermutlich existierenden dreidimensionalen Calabi-Yau Variet"aten mit $h^{1,1}=1$.

Smart magnetic dispersions - from switchable release to well-defined hybrid nanofibers

The synthesis, characterization and application of aqueous dispersions of superparamagnetic/polymer hybrid nanoparticles and capsules is described. Implementation of the superparamagnetic moiety into the polymer matrix enables a response of the nanomaterials towards an external magnetic field. Application of the external field is used for two main purposes: i) As heat generator, when an alternating magnetic field is applied. ii) As structuring agent to self-assemble superparamagnetic nanoparticles in the external field.rnIn the first part, superparamagnetic nanoparticles were used as heat generators in order to achieve a magnetic field induced release of an active compound from nanocontainers. To achieve such a release in remote-controlled fashion, the encapsulation of superparamagnetic nanoparticles into polymer nanocapsules was combined with the integration of a thermolabile compound into the shell of the nanocontainers. The magnetic nanoparticles acted as generators for heat, which decomposed the thermolabile compound. Pores were created in the degrading shell and an active substance was released.rn Additionally, the self-assembly of polymer nanoparticles, which were labeled with a superparamagnetic moiety as structuring agent, could be demonstrated. A combination of a magnetic field induced self-assembly and a sintering of neighboring particles upon an increase in temperature above the glass transition temperature of the polymer was used to form stable architectures. Various structures with tunable periodicity could be obtained ranging from smooth linear nanofibers to zigzag fibers. Besides solely creating linear architectures, the frugal process additionally allowed the creation of arrangements in analogy to more complex polymer architectures: By the introduction of defined junction points, the generation of branched structures and networks was demonstrated. Additionally, by tailoring the interaction of differently sized particles, the preparation of nanoparticle arrangements in statistical or block copolymer fashion was shown. Moreover, a reversible linear assembly and linkage of the nanoparticles was demonstrated following a lock/unlock mechanism. Therefore, the particles were locked in their linear assembly by a stable iron(III) hydroxamato-complex and unlocked by addition of a reducing agent and formation of a less stable iron(II)-complex.Further, in various projects with collaboration partners, nanoparticles and nanocapsules were labeled with a superparamagnetic moiety for their use as contrast agents in magnetic resonance imaging or as magnetically separable dispersions.

Investigation of acceptor dopants in ZrNiSn half-Heusler materials

Thermoelectric generators (TEG) are solid state devices and are able to convert thermal energy directly into electricity and thus could play an important role in waste heat recovery in the near future. Half-Heusler (HH) compounds with the general formula MNiSn (M = Ti, Zr, Hf) built a promising class of materials for these applications because of their high Seebeck coefficients, their environmentally friendliness and their cost advantage over conventional thermoelectric materials.rnrnMuch of the existing literature on HH deals with thermoelectric characterization of n-type MNiSn and p-type MCoSb compounds. Studies on p-type MNiSn-based HHs are far fewer in number. To fabricate high efficient thermoelectric modules based on HH compounds, high performance p-type MNiSn systems need to be developed that are compatible with the existing n-type HH compounds. This thesis explores synthesis strategies for p-type MNiSn based compounds. In particular, the efficacy of transition metals (Sc, La) and main group elements (Al, Ga, In) as acceptor dopants on the Sn-site in ZrNiSn, was investigated by evaluating their thermoelectric performance. The most promising p-type materials could be achieved with transition metal dopants, where the introduction of Sc on the Zr side, yielded the highest Seebeck coefficient in a ternary NiSn-based HH compound up to this date. Hall effect and band gap measurements of this system showed, that the high mobility of minority carrier electrons dominate the transport properties at temperatures above 500 K. It could be shown that this is the reason, why n-type HH are successful TE materials for high temperature applications, and that p-types are subjected to bipolar effects which will lead to diminished thermoelectric efficiencies at high temperatures.rnrnTo complement the experimental investigations on different metal dopants and their influence on the TE properties of HH compounds, numerical solutions to the Boltzmann transport equation were used to predict the optimum carrier concentration where the maximum TE efficiency occurs for p-type HH compounds. The results for p-type samples showed that can not be treated within a simple parabolic band model approach, due to bipolar and multi-band effects.rnrnThe parabolic band model is commonly used for bulk TE materials. It is most accurate when the transport properties are dominated by one single carrier type. Since the transport properties of n-type HH are dominated by only one carrier type (high mobility electrons), it could be shown, that the use of a simple parabolic band model lead to a successful prediction of the optimized carrier concentration and thermoelectric efficiency in n-type HH compounds. rn

High-mass Drell-Yan cross-section and search for new phenomena in multi-electron/positron final states with the ATLAS detector

The Standard Model of particle physics is a very successful theory which describes nearly all known processes of particle physics very precisely. Nevertheless, there are several observations which cannot be explained within the existing theory. In this thesis, two analyses with high energy electrons and positrons using data of the ATLAS detector are presented. One, probing the Standard Model of particle physics and another searching for phenomena beyond the Standard Model.rnThe production of an electron-positron pair via the Drell-Yan process leads to a very clean signature in the detector with low background contributions. This allows for a very precise measurement of the cross-section and can be used as a precision test of perturbative quantum chromodynamics (pQCD) where this process has been calculated at next-to-next-to-leading order (NNLO). The invariant mass spectrum mee is sensitive to parton distribution functions (PFDs), in particular to the poorly known distribution of antiquarks at large momentum fraction (Bjoerken x). The measurementrnof the high-mass Drell-Yan cross-section in proton-proton collisions at a center-of-mass energy of sqrt(s) = 7 TeV is performed on a dataset collected with the ATLAS detector, corresponding to an integrated luminosity of 4.7 fb-1. The differential cross-section of pp -> Z/gamma + X -> e+e- + X is measured as a function of the invariant mass in the range 116 GeV < mee < 1500 GeV. The background is estimated using a data driven method and Monte Carlo simulations. The final cross-section is corrected for detector effects and different levels of final state radiation corrections. A comparison isrnmade to various event generators and to predictions of pQCD calculations at NNLO. A good agreement within the uncertainties between measured cross-sections and Standard Model predictions is observed.rnExamples of observed phenomena which can not be explained by the Standard Model are the amount of dark matter in the universe and neutrino oscillations. To explain these phenomena several extensions of the Standard Model are proposed, some of them leading to new processes with a high multiplicity of electrons and/or positrons in the final state. A model independent search in multi-object final states, with objects defined as electrons and positrons, is performed to search for these phenomenas. Therndataset collected at a center-of-mass energy of sqrt(s) = 8 TeV, corresponding to an integrated luminosity of 20.3 fb-1 is used. The events are separated in different categories using the object multiplicity. The data-driven background method, already used for the cross-section measurement was developed further for up to five objects to get an estimation of the number of events including fake contributions. Within the uncertainties the comparison between data and Standard Model predictions shows no significant deviations.

Thermoelectric performance of p-type TiCoSb half-Heusler compounds - Intrinsic phase separation and charge carrier concentration optimization as key to high efficiency

The world's rising demand of energy turns the development of sustainable and more efficient technologies for energy production and storage into an inevitable task. Thermoelectric generators, composed of pairs of n-type and p-type semiconducting materials, di¬rectly transform waste heat into useful electricity. The efficiency of a thermoelectric mate¬rial depends on its electronic and lattice properties, summarized in its figure of merit ZT. Desirable are high electrical conductivity and Seebeck coefficients, and low thermal con¬ductivity. Half-Heusler materials are very promising candidates for thermoelectric applications in the medium¬ temperature range such as in industrial and automotive waste heat recovery. The advantage of Heusler compounds are excellent electronic properties and high thermal and mechanical stability, as well as their low toxicity and elemental abundance. Thus, the main obstacle to further enhance their thermoelectric performance is their relatively high thermal conductivity.rn rnIn this work, the thermoelectric properties of the p-type material (Ti/Zr/Hf)CoSb1-xSnx were optimized in a multistep process. The concept of an intrinsic phase separation has recently become a focus of research in the compatible n-type (Ti/Zr/Hf)NiSn system to achieve low thermal conductivities and boost the TE performance. This concept is successfully transferred to the TiCoSb system. The phase separation approach can form a significant alternative to the previous nanostructuring approach via ball milling and hot pressing, saving pro¬cessing time, energy consumption and increasing the thermoelectric efficiency. A fundamental concept to tune the performance of thermoelectric materials is charge carrier concentration optimization. The optimum carrier concentration is reached with a substitution level for Sn of x = 0.15, enhancing the ZT about 40% compared to previous state-of-the-art samples with x = 0.2. The TE performance can be enhanced further by a fine-tuning of the Ti-to-Hf ratio. A correlation of the microstructure and the thermoelectric properties is observed and a record figure of merit ZT = 1.2 at 710°C was reached with the composition Ti0.25Hf0.75CoSb0.85Sn0.15.rnTowards application, the long term stability of the material under actual conditions of operation are an important issue. The impact of such a heat treatment on the structural and thermoelectric properties is investigated. Particularly, the best and most reliable performance is achieved in Ti0.5Hf0.5CoSb0.85Sn0.15, which reached a maximum ZT of 1.1 at 700°C. The intrinsic phase separation and resulting microstructure is stable even after 500 heating and cooling cycles.

Groups Acting on Tensor Products

Groups preserving a distributive product are encountered often in algebra. Examples include automorphism groups of associative and nonassociative rings, classical groups, and automorphism groups of p-groups. While the great variety of such products precludes any realistic hope of describing the general structure of the groups that preserve them, it is reasonable to expect that insight may be gained from an examination of the universal distributive products: tensor products. We give a detailed description of the groups preserving tensor products over semisimple and semiprimary rings, and present effective algorithms to construct generators for these groups. We also discuss applications of our methods to algorithmic problems for which all currently known methods require an exponential amount of work. (C) 2013 Elsevier B.V. All rights reserved.

Effects of transcranial direct current stimulation (tDCS) on behaviour and electrophysiology of language production

Excitatory anodal transcranial direct current stimulation (A-tDCS) over the left dorsal prefrontal cortex (DPFC) has been shown to improve language production. The present study examined neurophysiological underpinnings of this effect. In a single-blinded within-subject design, we traced effects of A-tDCS compared to sham stimulation over the left DPFC using electrophysiological and behavioural correlates during overt picture naming. Online effects were examined during A-tDCS by employing the semantic interference (SI-)Effect – a marker that denotes the functional integrity of the language system. The behavioural SI-Effect was found to be reduced, whereas the electrophysiological SI-Effect was enhanced over left compared to right temporal scalp-electrode sites. This modulation is suggested to reflect a superior tuning of neural responses within language-related generators. After -(offline) effects of A-tDCS were detected in the delta frequency band, a marker of neural inhibition. After A-tDCS there was a reduction in delta activity during picture naming and the resting state, interpreted to indicate neural disinhibition. Together, these findings demonstrate electrophysiological modulations induced by A-tDCS of the left DPFC. They suggest that A-tDCS is capable of enhancing neural processes during and after application. The present functional and oscillatory neural markers could detect positive effects of prefrontal A-tDCS, which could be of use in the neuro-rehabilitation of frontal language functions.

Epileptogenic developmental venous anomaly: insights from simultaneous EEG/fMRI

Developmental venous anomalies (DVAs) are associated with epileptic seizures; however, the role of DVA in the epileptogenesis is still not established. Simultaneous interictal electroencephalogram/functional magnetic resonance imaging (EEG/fMRI) recordings provide supplementary information to electroclinical data about the epileptic generators, and thus aid in the differentiation of clinically equivocal epilepsy syndromes. The main objective of our study was to characterize the epileptic network in a patient with DVA and epilepsy by simultaneous EEG/fMRI recordings. A 17-year-old woman with recently emerging generalized tonic-clonic seizures, and atypical generalized discharges, was investigated using simultaneous EEG/fMRI at the university hospital. Previous high-resolution MRI showed no structural abnormalities, except a DVA in the right frontal operculum. Interictal EEG recordings showed atypical generalized discharges, corresponding to positive focal blood oxygen level dependent (BOLD) correlates in the right frontal operculum, a region drained by the DVA. Additionally, widespread cortical bilateral negative BOLD correlates in the frontal and parietal lobes were delineated, resembling a generalized epileptic network. The EEG/fMRI recordings support a right frontal lobe epilepsy, originating in the vicinity of the DVA, propagating rapidly to both frontal and parietal lobes, as expressed on the scalp EEG by secondary bilateral synchrony. The DVA may be causative of focal epilepsies in cases where no concomitant epileptogenic lesions can be detected. Advanced imaging techniques, such as simultaneous EEG/fMRI, may thus aid in the differentiation of clinically equivocal epilepsy syndromes.

Effects of amygdala-hippocampal stimulation on interictal epileptic discharges

Deep brain stimulation (DBS) of different nuclei is being evaluated as a treatment for epilepsy. While encouraging results have been reported, the effects of changes in stimulation parameters have been poorly studied. Here the effects of changes of pulse waveform in high frequency DBS (130 Hz) of the amygdala-hippocampal complex (AH) are presented. These effects were studied on interictal epileptic discharge rates (IEDRs). AH-DBS was implemented with biphasic versus pseudo monophasic charge balanced pulses, in two groups of patients: six with temporal lobe epilepsy (TLE) associated with hippocampal sclerosis (HS) and six with non lesional (NLES) temporal epilepsy. In patients with HS, IEDRs were significantly reduced with AH-DBS applied with biphasic pulses in comparison with monophasic pulse. IEDRs were significantly reduced in only two patients with NLES independently to stimulus waveform. Comparison to long-term seizure outcome suggests that IEDRs could be used as a neurophysiological marker of chronic AH-DBS and they suggest that the waveform of the electrical stimuli can play a major role in DBS. We concluded that biphasic stimuli are more efficient than pseudo monophasic pulses in AH-DBS in patients with HS. In patients with NLES epilepsy, other parameters relevant for efficacy of DBS remain to be determined.

Sonographic Assessment of the Umbilical Cord

The umbilical cord is not an inert structure, suspended between the fetus and placenta, but it plays an active role and it is involved in several processes afflicting the feto-placental unit. Its study has to be regarding not only its morphology and morphometry, and the impendance of blood flow by Doppler waveform analysis, but it includes also an analysis of the coiling type and the amount of the Wharton Jelly. The umbilical cord has been considered like an important and huge source of informations, useful to assess the well-being of the fetus and the outcome of pregnancy. The standardization of ultrasound techniques is the first step to speak the same language and make the study of this structure a fundamental part of well-being fetus assessment. This article is carefully focused on morphologic, morphometric and functional ultrasound examination of umbilical cord and suggests that any anomaly detected should provide an indication for an intense fetal follow-up, useful for early helpful therapy, preventing serious complication for the pregnancy.

Central venous pulse pressure analysis using an R-synchronized pressure measurement system

Objective. The information derived from central venous catheters is underused. We developed an EKG-R synchronization and averaging system to obtained distinct CVP waveforms and analyzed components of these. Methods. Twenty-five paralyzed surgical patients undergoing CVP monitoring under mechanical ventilation were studied. CVP and EKG signals were analyzed employing our system, the mean CVP and CVP at end-diastole during expiration were compared, and CVP waveform components were measured using this system. Results. CVP waveforms were clearly visualized in all patients. They showed the a peak to be 1.8+/- 0.7 mmHg, which was the highest of three peaks, and the x trough to be lower than the y trough (-1.6+/- 0.7mmHgand-0.9+/- 0.5mmHg, respectively), withameanpulsepressureof3.4mmHg.ThedifferencebetweenthemeanCVPandCVPatend-diastoleduringexpirationwas0.58+/- 0.81 mmHg. Conclusions. The mean CVP can be used as an index of right ventricular preload in patients under mechanical ventilation with regular sinus rhythm. Our newly developed system is useful for clinical monitoring and for education in circulatory physiology.