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Exposure to fine and ultra-fine environmental particles is still a problem of concern in many industrialized parts of the world and the intensified use of nanotechnology may further increase exposure to small particles. Since many years air pollution is recognized as a critical problem in western countries, which led to rigorous regulation of air quality and the introduction of strict guidelines. However, the upper thresholds for particulates in ambient air recommended by the world health organization are often exceeded several times in newly industrialized countries. Such high levels of air pollution have the potential to induce adverse effects on human health. The response triggered by air pollutants is not limited to local effects of the respiratory system but is often systemic, resulting in endothelial dysfunction or atherosclerotic malady. The link between air pollution and cardiovascular disease is now accepted by the scientific community but the underlying mechanisms responsible for the pro-atherogenic potential still need to be unraveled in detail. Based on the results from in- vivo and in vitro studies the production of reactive oxygen species due to exposure to particles is the most important mechanism to explain the observed adverse effects. However, the doses that were applied in many in vivo and in vitro studies are far beyond the range of what humans are exposed to and there is the need for more realistic exposure studies. Complex in vitro coculture systems may be valuable tools to study particle-induced processes and to extrapolate effects of particles on the lung. One of the objectives of this PhD thesis was the establishment and further improvement of a complex coculture system initially described by Alfaro-Moreno et al. [1]. The system is composed of an alveolar type-II cell line (A549), differentiated macrophage-like cells (THP-1), mast cells (HMC-1) and endothelial cells (EA.hy 926), seeded in a 3D-orientation on a microporous membrane to mimic the cell response of the alveolar surface in vitro in conjunction with native aerosol exposure (VitrocellTM chamber). The tetraculture system was carefully characterized to ensure its performance and repeatability of results. The spatial distribution of the cells in the tetraculture was analyzed by confocal laser scanning microscopy (CLSM), showing a confluent layer of endothelial and epithelial cells on both sides of the Transwellâ„¢. Macrophage-like cells and mast cells can be found on top of the epithelial cells. The latter cells formed colonies under submerged conditions, which disappeared at the air-liquid-interface (ALI). The VitrocellTM aerosol exposure system was not significantly influencing the viability. Using this system, cells were exposed to an aerosol of 50 nm SiO2-Rhodamine nanoparticles (NPs) in PBS. The distribution of the NPs in the tetraculture after exposure was evaluated by CLSM. Fluorescence from internalized particles was detected in CD11b-positive THP-1 cells only. Furthermore, all cell lines were found to be able to respond to xenobiotic model compounds, such as benzo[a]pyrene (B[a]P) or 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) with the upregulation of CYP1 mRNA. With this tetraculture system the response of the endothelial part of the alveolar barrier was studied in- vitro in a still realistic exposure scenario representing the conditions for a polluted situation without direct exposure of endothelial cells. After exposure to diesel exhaust particulate matter (DEPM) the expression of different anti-oxidant target genes and inflammatory genes such as NAD(P)H dehydrogenase quinone 1 (NQO1), superoxide dismutase 1 (SOD1) and heme oxygenase 1 (HMOX1), as well as the nuclear translocation nuclear factor erythroid-derived 2 (Nrf2) was evaluated. In addition, the potential of DEPM to induce the upregulation of CYP1A1 mRNA in the endothelium was analyzed. DEPM exposure led not to an upregulation of the anti-oxidant or inflammatory target genes, but to clear nuclear translocation of Nrf2. The endothelial cells responded to the DEPM treatment also with the upregulation of CYP1A1 mRNA and nuclear translocation of the aryl hydrocarbon receptor (AhR). Overall, DEPM triggered a response in the endothelial cells after indirect exposure of the tetraculture system to low doses of DEPM, underlining the sensitivity of ALI exposure systems. The use of the tetraculture together with the native aerosol exposure equipment may finally lead to a more realistic judgment regarding the hazard of new compounds and/or new nano-scaled materials in the future. For the first time, it was possible to study the response of the endothelial cells of the alveolar barrier in vitro in a realistic exposure scenario avoiding direct exposure of endothelial cells to high amounts of particulates.
The main achievement of this thesis is an analysis of the accuracy of computations with Loader's algorithm for the binomial density. This analysis in later progress of work could be used for a theorem about the numerical accuracy of algorithms that compute rectangle probabilities for scan statistics of a multinomially distributed random variable. An example that shall illustrate the practical use of probabilities for scan statistics is the following, which arises in epidemiology: Let n patients arrive at a clinic in d = 365 days, each of the patients with probability 1/d at each of these d days and all patients independently from each other. The knowledge of the probability, that there exist 3 adjacent days, in which together more than k patients arrive, helps deciding, after observing data, if there is a cluster which we would not suspect to have occurred randomly but for which we suspect there must be a reason. Formally, this epidemiological example can be described by a multinomial model. As multinomially distributed random variables are examples of Markov increments, which is a fact already used implicitly by Corrado (2011) to compute the distribution function of the multinomial maximum, we can use a generalized version of Corrado's Algorithm to compute the probability described in our example. To compute its result, the algorithm for rectangle probabilities for Markov increments always uses transition probabilities of the corresponding Markov Chain. In the multinomial case, the transition probabilities of the corresponding Markov Chain are binomial probabilities. Therefore, we start an analysis of accuracy of Loader's algorithm for the binomial density, which for example the statistical software R uses. With the help of accuracy bounds for the binomial density we would be able to derive accuracy bounds for the computation of rectangle probabilities for scan statistics of multinomially distributed random variables. To figure out how sharp derived accuracy bounds are, in examples these can be compared to rigorous upper bounds and rigorous lower bounds which we obtain by interval-arithmetical computations.
Das Triple-X-Syndrom ist die häufigste Chromosomenstörung im weiblichen Geschlecht und dennoch wenig bekannt und erforscht. Um die wissenschaftliche Datenlage für die Betroffenen, werdenden Eltern und genetischen Berater zu verbessern wurde die vorliegende Studie durchgeführt. Ziel der Studie war es zu untersuchen, ob bei Mädchen und Frauen mit Triple-X-Karyotyp häufiger psychische Probleme und Verhaltensauffälligkeiten auftreten als bei Mädchen und Frauen mit einem regelrechten Chromosomensatz. Insgesamt konnten 72 Mädchen und Frauen mit Triple-X und 69 mit einem regelrechten Chromosomensatz in die Studie eingeschlossen werden. Durch drei in Altersgruppen aufgeteilte Kohorten konnte verglichen werden, ob mögliche Auffälligkeiten altersabhängig auftreten, wie sich der Entwicklungsverlauf vom Kind zur erwachsenen Frau darstellt und ob dabei Zusammenhänge erkennbar sind. Bei den Mädchen im Alter von vier bis sieben Jahren zeigten sich im Vergleich zur Kontrollgruppe bereits signifikante Unterschiede in Bezug auf schulische Kompetenzen, soziale Probleme und Aufmerksamkeitsprobleme. In der Altersgruppe der Mädchen von acht bis 17 Jahren haben sich diese Auffälligkeiten noch verstärkt und die Ergebnisse aus dem Fragebogen "Child Behavior Checklist" weisen über alle Skalen hinweg einen deutlichen Unterschied zwischen der Triple-X-Gruppe und der Kontrollgruppe auf. Dies betrifft insbesondere die Bereiche "Schulische Kompetenzen", "Internalisierende Auffälligkeiten", "Sozialer Rückzug", "Soziale Probleme" und "Aufmerksamkeits-probleme". In der Gesamtintensität der Auffälligkeiten haben die Triple-X-Mädchen im Mittel signifikant schlechtere Werte als die Mädchen der Kontrollgruppe. Auch ist der Anteil der Mädchen, die in den klinisch auffälligen Bereich fallen, in der Triple-X-Gruppe signifikant erhöht. Die Untersuchungen zum Selbstwertgefühl machen deutlich, dass Mädchen mit Triple-X-Karyotyp ein vermindertes Selbstwertgefühl im Vergleich zur Kontrollgruppe aufweisen. Auch unterscheiden sich Triple-X-Mädchen in Bezug auf ihr Emotionsregulationsverhalten. Sie haben eine Tendenz zu eher maladaptiven Bewältigungsstrategien und sie zeigen insbesondere beim "Problemorientierten Handeln" und auch in Bezug auf die Emotion "Angst" signifikante Unterschiede zur Kontrollgruppe. Für die Gruppe der Erwachsenen konnte nachgewiesen werden, dass sich Triple-X-Frauen in ihren Persönlichkeitsmerkmalen von Frauen mit einem regelrechten Chromosomensatz unterscheiden. Die Ergebnisse lassen darauf schließen, dass Triple-X-Frauen häufiger emotional labil und ängstlich reagieren und auch eher zurückhaltend und introvertiert und weniger leistungsorientiert sind. Sie haben eine geringere Lebenszufriedenheit und neigen dazu weniger sozial verantwortlich zu handeln. Triple-X-Frauen sind in ihrem täglichen Leben stärker durch körperliche und psychische Symptome beeinträchtigt, wenngleich diese Beeinträchtigungen nicht so stark sind, dass sie in den klinisch auffälligen Bereich fallen.
Ausgehend von einem multifaktoriellen biopsychosozialen Modell zur Entstehung und Aufrechterhaltung primärer Kopfschmerzen bei Kindern und Jugendlichen wurden n= 170 Mädchen im Alter von 12-17 Jahren hinsichtlich verschiedener stressbezogener Determinanten untersucht. Es wurde davon ausgegangen, dass sich Mädchen mit wiederkehrenden Kopfschmerzen sowohl in einem kontrollierten, messwiederholten Laborexperiment hinsichtlich ihrer physiologischen Reaktionen (Muskelspannung, Cortisolausschüttung) auf akuten Stress hin wie auch in der Cortisolaufwachreaktion im häuslichen Setting von einer gesunden Kontrollgruppe unterscheiden. Diese Annahmen konnten nach statistischer Auswertung der Studienergebnisse unter Kontrolle der familiären Schmerzbelastung und psychischen Stressbelastung jedoch nicht bestätigt werden. Somit kann nicht von einer dysregulierten Aktivität der Hypothalamus-Hypophysen-Nebennierenrinden-Achse ausgegangen werden, die eine zentrale Rolle in der biologischen Stressantwort spielt und auch die Schmerzverarbeitung mit beeinflusst. Ebenso wenig liegt bei Mädchen mit Kopfschmerzen eine erhöhte basale oder stressbedingte Muskelspannung im Kopf- und Schulterbereich vor. Lediglich auf subjektiver Ebene deutete sich ein tendenziell höheres Empfinden von Anspannung in Ruhephasen an. Auf psychologischer Ebene hingegen zeigte sich erwartungskonform eine höhere Stress-vulnerabilität bei den Mädchen mit Kopfschmerzen. Außerdem wurde bei ihnen der vermehrte Einsatz emotionsregulierender Stressbewältigungsstrategien, wie Ruhe und Entspannung, aber auch destruktiv-ärgerbezogenes Verhalten und Denken, bezogen auf soziale und leistungsbezogene Stresssituationen beobachtet. Auch unterschieden sie sich hinsichtlich der familiären Schmerzbelastung, körperlichen und psychischen Stress-symptomatik und Depressivität sowie Ängstlichkeit von der Kontrollgruppe. Sie zeigten durchweg höhere Ausprägungen auf diesen Variablen, die sich als signifikante Prädiktoren für Kopfschmerzen herausstellten. Die Verknüpfung von physiologischen Reaktionsmaßen mit der Stressverarbeitung zeigte, dass die Nutzung von konstruktiv-palliativer Emotionsregulation umso stärker ist, je höher der stressbedingte Anstieg der Cortisolausschüttung und der Muskelaktivität in der Frontalisregion ausfällt. Je stärker also die körperliche Reaktion auf Stress, umso mehr versuchen jugendliche Mädchen sich zu entspannen und auszuruhen.
The equity premium (Mehra and Prescott, 1985) is still a puzzle in the sense that there are still no convincing explanations for the size of the equity premium. In this dissertation, we study this long-standing puzzle and several possible behavioral explanations. First, we apply the IRR methodology proposed by Fama and French (1999) to achieve large firm level data on the equity premia for N = 28,256 companies in 54 countries around the world. Second, by using preferences data from the INTRA study (Rieger et. al., 2014), we could test the relevant risk factors together with time cognition to explain the equity premium. We document the failure of the Myopic Loss Aversion hypothesis by Benartzi and Thaler (1995) but provides rigorous empirical evidence to support the behavioral theory of ambiguity aversion to account for the equity premium. The observations shed some light on the new approach of integrating risk and ambiguity (together with time preferences) into a more general model of uncertainty, in which both risk premium and ambiguity premium play roles in asset pricing models.
The present work considers the normal approximation of the binomial distribution and yields estimations of the supremum distance of the distribution functions of the binomial- and the corresponding standardized normal distribution. The type of the estimations correspond to the classical Berry-Esseen theorem, in the special case that all random variables are identically Bernoulli distributed. In this case we state the optimal constant for the Berry-Esseen theorem. In the proof of these estimations several inequalities regarding the density as well as the distribution function of the binomial distribution are presented. Furthermore in the estimations mentioned above the distribution function is replaced by the probability of arbitrary, not only unlimited intervals and in this new situation we also present an upper bound.
Phase-amplitude cross-frequency coupling is a mechanism thought to facilitate communication between neuronal ensembles. The mechanism could underlie the implementation of complex cognitive processes, like executive functions, in the brain. This thesis contributes to answering the question, whether phase-amplitude cross-frequency coupling - assessed via electroencephalography (EEG) - is a mechanism by which executive functioning is implemented in the brain and whether an assumed performance effect of stress on executive functioning is reflected in phase-amplitude coupling strength. A huge body of studies shows that stress can influence executive functioning, in essence having detrimental effects. In two independent studies, each being comprised of two core executive function tasks (flexibility and behavioural inhibition as well as cognitive inhibition and working memory), beta-gamma phase-amplitude coupling was robustly detected in the left and right prefrontal hemispheres. No systematic pattern of coupling strength modulation by either task demands or acute stress was detected. Beta-gamma coupling might also be present in more basic attention processes. This is the first investigation of the relationship between stress, executive functions and phase-amplitude coupling. Therefore, many aspects have not been explored yet. For example, studying phase precision instead of coupling strength as an indicator for phase-amplitude coupling modulations. Furthermore, data was analysed in source space (independent component analysis); comparability to sensor space has still to be determined. These as well as other aspects should be investigated, due to the promising finding of very robust and strong beta-gamma coupling for all executive functions. Additionally, this thesis tested the performance of two widely used phase-amplitude coupling measures (mean vector length and modulation index). Both measures are specific and sensitive to coupling strength and coupling width. The simulation study also drew attention to several confounding factors, which influence phase-amplitude coupling measures (e. g. data length, multimodality).
Global food security poses large challenges to a fast changing human society and has been a key topic for scientists, agriculturist, and policy makers in the 21st century. The United Nation predicts a total world population of 9.15 billion in 2050 and defines the provision of food security as the second major point in the UN Sustainable Development Goals. As the capacities of both, land and water resources, are finite and locally heavily overused, reducing agriculture’s environmental impact while meeting an increasing demand for food of a constantly growing population is one of the greatest challenges of our century. Therefore, a multifaceted solution is required, including approaches using geospatial data to optimize agricultural food production.
The availability of precise and up-to-date information on vegetation parameters is mandatory to fulfill the requirements of agricultural applications. Direct field measurements of such vegetation parameters are expensive and time-consuming. On the contrary, remote sensing offers a variety of techniques for a cost-effective and non-destructive retrieval of vegetation parameters. Although not widely used, hyperspectral thermal infrared (TIR) remote sensing has demonstrated being a valuable addition to existing remote sensing techniques for the retrieval of vegetation parameters.
This thesis examined the potential of TIR imaging spectroscopy as an important contribution to the growing need of food security. The main scientific question dealt with the extraction of vegetation parameters from imaging TIR spectroscopy. To this end, two studies impressively demonstrated the ability of extracting vegetation related parameters from leaf emissivity spectra: (i) the discrimination of eight plant species based on their emissivity spectra and (ii) the detection of drought stress in potato plants using temperature measures and emissivity spectra.
The datasets used in these studies were collected using the Telops Hyper-Cam LW, a novel imaging spectrometer. Since this FTIR spectrometer presents some particularities, special attention was paid on the development of dedicated experimental data acquisition setups and on data processing chains. The latter include data preprocessing and the development of algorithms for extracting precise surface temperatures, reproducible emissivity spectra and, in the end, vegetation parameters.
The spectrometer’s versatility allows the collection of airborne imaging spectroscopy datasets. Since the general availability of airborne TIR spectrometers is limited, the preprocessing and
data extraction methods are underexplored compared to reflective remote sensing. This counts especially for atmospheric correction (AC) and temperature and emissivity separation (TES) algorithms. Therefore, we implemented a powerful simulation environment for the development of preprocessing algorithms for airborne hyperspectral TIR image data. This simulation tool is designed in a modular way and includes the image data acquisition and processing chain from surface temperature and emissivity to the final at-sensor radiance data. It includes a series of available algorithms for TES, AC as well as combined AC and TES approaches. Using this simulator, one of the most promising algorithms for the preprocessing of airborne TIR data – ARTEMISS – was significantly optimized. The retrieval error of the atmospheric water vapor during the atmospheric characterization was reduced. As a result, this improvement in atmospheric characterization accuracy enhanced the subsequent retrieval of surface temperatures and surface emissivities intensely.
Although, the potential of hyperspectral TIR applications in ecology, agriculture, and biodiversity has been impressively demonstrated, a serious contribution to a global provision of food security requires the retrieval of vegetation related parameters with global coverage, high spatial resolution and at high revisit frequencies.
Emerging from the findings in this thesis, the spectral configuration of a spaceborne TIR spectrometer concept was developed. The sensors spectral configuration aims at the retrieval of precise land surface temperatures and land surface emissivity spectra. Complemented with additional characteristics, i.e. short revisit times and a high spatial resolution, this sensor potentially allows the retrieval of valuable vegetation parameters needed for agricultural optimizations. The technical feasibility of such a sensor concept underlines the potential contribution to the multifaceted solution required for achieving the challenging goal of guaranteeing global food security in a world of increasing population.
In conclusion, thermal remote sensing and more precisely hyperspectral thermal remote sensing has been presented as a valuable technique for a variety of applications contributing to the final goal of a global food security.
Fehlende Werte und deren Kompensation über Imputation stellen eine große Herausforderung für die Varianzschätzung eines Punktschätzers dar. Dies gilt auch in der Amtlichen Statistik. Um eine unverzerrte Varianzschätzung zu gewährleisten, müssen alle Komponenten der Varianz berücksichtigt werden. Hierzu wird häufig eine Zerlegung der Gesamtvarianz durchgeführt mit dem Ziel, detaillierte Informationen über ihre Komponenten zu erhalten und diese vollständig zu erfassen. In dieser Arbeit stehen Resampling-Methoden im Vordergrund. Es wird ein Ansatz entwickelt, wie neuere Resampling-Methoden, welche alle Elemente der ursprünglichen Stichprobe berücksichtigen, hinsichtlich der Anwendung von Imputation übertragen werden können. Zum Vergleich verschiedener Varianzschätzer wird eine Monte-Carlo-Simulationsstudie durchgeführt. Mit Hilfe einer Monte-Carlo-Simulation findet zudem eine Zerlegung der Gesamtvarianz unter verschiedenen Parameterkonstellationen statt.