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Gewitterzellen mit ihren negativen Begleiterscheinungen wie Starkregen, Hagel oder Fallwinden verursachen Verspätungen sowie Flugausfälle und sind damit für höhere Kosten der Airlines und Flughafenbetreiber verantwortlich. Eine verlässliche Vorhersage von Gewittern bis zu mehreren Stunden könnte dagegen den Entscheidungsträgern am Flughafen einen größeren zeitlichen Spielraum geben, um auf mögliche Gewitterzellen angemessen zu reagieren und adäquate Maßnahmen zu ergreifen. Zur Bereitstellung zuverlässiger Gewittervorhersagen bis zu sechs Stunden wurde Cb-LIKE am Deutschen Zentrum für Luft- und Raumfahrt (DLR) entwickelt. Der neue Gewittervorhersagealgorithmus wird in der vorliegenden Dissertation detailliert vorgestellt. Cb-LIKE ist ein automatisiertes System, das unter Verwendung von Modelldaten des COSMO-DE Wettermodells des Deutschen Wetterdienstes (DWD) Gebiete ausweist, die eher für oder gegen eine Entwicklung von Gewittern sprechen. Vier atmosphärische Parameter (CAPE, Vertikalwind, Radarreflektivität und Temperatur an der Wolkenobergrenze) fließen in das System ein. Eine neu entwickelte „Best-Member-Selection“ sorgt dabei durch einen Abgleich zur aktuellen Gewittersituation für die automatische Auswahl des realistischsten Modelllaufes aus einem Ensemble. Dadurch wird die beste Datengrundlage für die Berechnung der Gewittervorhersagen gewährleistet. Für die Auswahl des besten Members stehen vier verschiedene Modi zur Verfügung. Ein neu entwickeltes Fuzzy-Logik System ermöglicht anschließend die Kombination der Modelldaten und die Berechnung eines Gewitterindikators von 11,6¯6 bis 88,3¯3 für jeden Gitterpunkt des Modells für die nächsten sechs Stunden in stündlichen Intervallen. Je höher der Wert des Indikators, desto mehr sprechen die Modellparameter für die Entstehung von Gewittern. Zusätzlich wird die Vorhersagequalität des neuen Algorithmus anhand einer umfassenden Verifikation unter Verwendung einer „neighbourhood-verification“ Technik und von „multi-event contingency tables“ untersucht. Für die Sommerperiode 2012 weist Cb-LIKE im Vergleich zur COSMO-DE Radarreflektivität bessere Werte in den Verifikationsgrößen auf. So ist das „Fehlalarmverhältnis“ für den neuen Algorithmus niedriger (0,48 zu 0,56), die „Wahrscheinlichkeit der Detektion“ (0,52 zu 0,45) und der „Critical Success Index“ (0,50 zu 0,48) fallen dagegen höher aus. Die Resultate zeigen, dass der Cb- LIKE Algorithmus eine sinnvolle neue Methodik für Gewittervorhersagen von hoher Qualität auf der Datenbasis des COSMO-DE Modells darstellt. Die Ergebnisse aus der Verifikation ermöglichen außerdem die Übersetzung des Cb-LIKE Indikatorfeldes in die gewünschten probabilistischen Gewittervorhersagen. Zusätzlich wird die erfolgreiche Implementierung der Cb-LIKE Gewittervorhersagen in das WxFUSION System, eine graphische Benutzeroberfläche, vorgestellt. / Thunderstorm cells with their adverse weather hazards like heavy rain, hail or downbursts cause delays and flight cancellations at airports and, as a negative result, the airlines and airport operators have to bear high additional cost. A reliable thunderstorm forecast up to several hours could provide more time for the decision makers at the airport for an appropriate reaction on possible storm cells and initiation of adequate counteractions. To provide the required thunderstorm forecasts up to six hours Cb-LIKE has been developed at the DLR (Deutsches Zentrum für Luft- und Raumfahrt) Institute of Atmospheric Physics. The development of the new algorithm is described in detail in the present dissertation. Cb-LIKE is an automated system which designates areas with possible thunderstorm development by using model data of the COSMO-DE numerical weather prediction model, which is driven by the German Meteorological Service (DWD). Four atmospheric parameters (CAPE, vertical wind velocity, radar reflectivity and cloud top temperature) of the model output are used within the system. A newly developed “Best-Member-Selection“ allows the automatic selection of that model run of a COSMO-DE model ensemble which matches best the observed storm situation. Thereby, the application of the best available data basis for the calculation of the thunderstorm forecasts is ensured. Altogether there are four different modes for the selection of the best member. A newly developed fuzzy logic system enables the subsequent combination of the model data and the calculation of a thunderstorm indicator within a value range of 11. ¯ 66 up to 88. ¯ 33 for each grid point of the model domain for the following six hours in hourly intervals. The higher the indicator the more the model parameters imply the development of thunderstorms. The forecasting quality of the new algorithm is demonstrated by a thorough verification using a neighborhood verification approach and multi-event contingency tables. For the summer period of 2012 Cb-LIKE shows better results in the verification scores in comparison to the COSMO-DE radar reflectivity. For example the new algorithm features a lower „False Alarm Ratio“ (0,48 to 0,56) and a higher „Probability of Detection“ (0,52 to 0,45) and „Critical Success Index“ (0,50 to 0,48). The results show that Cb-LIKE is a sensible novel approach to obtain probabilistic thunderstorm forecasts of high quality on the data basis of the COSMO-DE model. Finally, the implementation of the Cb-LIKE forecasts into the WxFUSION system which is a graphical user interface is presented.

Labile characters, like behaviors, are phenotypes that are expressed repeatedly in the life of an individual. These types of characters allow individuals to adjust their phenotype to various levels of environmental variation, and therefore play a key role in the evolutionary process. Labile phenotypes are distinct because of their multi-level nature; individuals can differ in their average phenotypic expression (causing among-individual variation), but they can also vary their phenotype in each expression (causing within-individual variation). In order to understand the role of labile characters in the evolutionary process it is necessary to acknowledge that variation at each level is caused by different processes. Variation at the among-individual level is caused by genetic or environmental differences having a permanent effect on an individual’s phenotype, whereas variation at the within-individual level is caused by an individual’s adjustment of its phenotype to a changing environment. The implications of these multi layered effects in the expression of labile characters have been acknowledged by different fields of evolutionary ecology, but major areas of evolutionary research do not fully incorporated this idea. The general aim of my thesis was to fully integrate this multi-level nature in the study of the adaptive causes and evolutionary consequences of variation in labile characters. My thesis is composed of five chapters: the first three are conceptual and methodological works aimed at integrating the multi-level nature of labile characters into already existing evolutionary frameworks. The last two chapters describe, as a worked example, how the different levels of variation and covariation between (labile) fertilization related traits affect the evolution of the alternative reproductive strategies in a wild passerine bird (the great tit). The first chapter is a conceptual work focusing on how to define and statistically characterize behavioral characters. We argue that behavioral characters can be studied using the “evolutionary character concept”. This framework was developed to study characters that only vary among individuals (i.e. “fixed characters”); therefore we extended this framework to include characters that also vary within-individuals. The second chapter of the thesis is a methodological work where we proposed a way to quantify multi-level variation in reaction norms, which allows the estimation of repeatability of plasticity. Behavioral ecologists have recently developed theory predicting the ecological conditions where repeatable vs. non-repeatable variation in phenotypic plasticity should evolve. However, there was no methodological framework to estimate repeatability of plasticity. Therefore, we proposed a study design and mixed effect model structure to estimate repeatability of plasticity. To help researchers use the proposed methodology, we developed an R simulation package to estimate bias, precision and accuracy for different sampling designs. The third chapter is an opinion paper that urges researchers to combine theory and methods developed in behavioral ecology and quantitative genetics to study phenotypic variation in a social context. Quantitative geneticists have developed a framework to study social evolution aimed at predicting the evolutionary response to selection of traits affected by the phenotypes of other individuals (the “social environment”). Phenotypes expressed in a social context, also called interactive phenotypes, exhibit a particular evolutionary dynamic because their environmental component is composed of genes and can thus evolve. Despite that fact that the effects of the social environment are commonly mediated by labile characters, this social evolution framework has not fully considered the multi-level nature of labile characters. Therefore, for chapter three we integrated the multi-level nature of labile characters in this social evolution framework. The final two chapters focus, as a worked example, on within-pair and extra-pair reproductive behavior in great tits. For these chapters, we utilized the theoretical and methodological developments of the previous chapters to study the sources of evolutionary constraints on alternative fertilization routes in male great tits. One of the chapters has a more evolutionary perspective, while the other applies a more behavioral ecology view point. In chapter four we studied male extra-pair and within-pair reproduction as interactive phenotypes that are affected by the phenotypes of both the male and the female member of great tit breeding pairs. We showed that male fertilization strategies depend heavily on the phenotype of their female. This social environment effect should influence the evolutionary response to selection of male fertilization strategies, and could partly explain evolutionary stasis, observed in natural populations, in traits so closely linked to fitness. In chapter four we also studied whether trade-offs among- or within-individuals can constrain the phenotypic evolution of male alternative reproductive strategies. We showed that among-male trade-offs between within-pair and extra-pair reproduction could also be a source of evolutionary constrain. In chapter five, we corroborated the existence of trade-offs between alternative reproductive routes by studying whether within-pair and extra-pair fertilizations are obtained at the same time, allowing for the possibility of a trade-off between the two. We found that a male's extra-pair fertilization success is actually higher when it constrains his ability to secure within-pair fertilizations. This result is consistent with our finding that there is indeed a trade-off between extra-pair and within-pair reproduction in this species. The empirical works in this thesis highlight the importance of the social environment as a source of phenotypic variation in the expression of labile traits. But more generally, from the works in this thesis, we can conclude that to fully understand the role of labile characters in the evolutionary process it is necessary to acknowledge their multi-level nature.

Over the past few decades, the generation of high energetic ion beams by relativistic intense laser pulses has attracted great attentions. Starting from the pioneering endeavors around 2000, several groups have demonstrated muliti-MeV (up to 58 MeV for proton by then) ion beams along with low transverse emittance and ps-scale pulse duration emitted from solid targets. Owing to those superior characteristics, laser driven ion beam is ideally suitable for many applications. However, the laser driven ion beam typically exhibits a large angular spread as well as a broad energy spectrum which for many applications is disadvantageous. The utilization of nano-targets as ion source provides a number of advantages over micrometer thick foils. The presented PhD work was intended to investigate laser driven ion acceleration from carbon nano-targets and demonstrate the potential feasibility for biological studies. Two novel nano-targets are employed: nm thin diamond-like-carbon (DLC) foil and carbon nanotubes foam (CNF). Both are self-produced in the technological laboratory at Ludwig-Maximilians-Universität München. Well-collimated proton beams with extremely small divergence (half angle) of 2 degrees are observed from DLC foils, one order of magnitude lower as compared to micrometer thick targets. Two-dimensional particle-in-cellsimulations indicate a strong influence from the electron density distribution on the divergence of protons. This interpretation is supported by an analytical model. In the same studies, the highest maximum proton energy was observed with a moderate laser intensity as low as 5*10^18W/cm^2. Parallel measurements of laser transmission and reflection are used to determine laser absorption in the nano-plasma, showing a strong correlation to the maximum proton energy. This observation indicates significance of absorbed laser energy rather than incident laser intensity and is supported by an analytical model. The ion energy also depends on pulse duration, a reduced optimum pulse duration is found as compared to micrometer thick targets. This behavior is attributed to a reduction of transverse electron spread due to the reduction of thickness from micrometer to nanometer. These remarkable proton bunch characteristics enabled irradiating living cells with a single shot dose of up to 7 Gray in one nanosecond, utilizing the Advanced Titanium: sapphire LASer (ATLAS)system at Max-Planck-Institut of Quantum Optics (MPQ). The experiments represent the first feasibility demonstration of a very compact laser driven nanosecond proton source for radiobiological studies by using a table-top laser system and advanced nano-targets. For the purpose of providing better ion sources for practical application, particularly in terms of energy increase, subsequent experiments were performed with the Astra Gemini laser system in the UK. The experiments demonstrate for the first time that ion acceleration can be enhanced by exploiting relativistic nonlinearities enabled by micrometer-thick CNF targets. When the CNF is attached to a nm-thick DLC foil, a significant increase of maximum carbon energy (up to threefold) is observed with circularly polarized laser pulses. A preferable enhancement of the carbon energy is observed with non-exponential spectral shape, indicating a strong contribution of the radiation pressure to the overall acceleration. In contrast, the linear polarization give rise to a more prominent proton acceleration. Proton energies could be increased by a factor of 2.4, inline with a stronger accelerating potential due to higher electron temperatures. Three-dimensional (3D) particle-in-cell (PIC) simulations reveal that the improved performance of the double-layer targets (CNF+DLC) can be attributed to relativistic self-focusing in near-critical density plasma. Interestingly, the nature of relativistic non-linearities, that plays a major role in laserwakefield-acceleration of electrons, can also apply to the benefit of laser driven ion acceleration.

No description available.

Evaluation of laminitis cases relies on radiographic measurements of the equine foot. Reference values have not been established for all layers of the foot. To establish normal hoof wall and sole measurements using digital radiography (DR) and magnetic resonance imaging (MRI) and to document tissue components present in the dorsal hoof wall and solar layers seen on DR. Prospective observational case–control study. Digital radiography and MRI were performed on 50 cadaver front feet from 25 horses subjected to euthanasia for nonlameness-related reasons. Four observers measured hoof wall (dorsal, lateral and medial) and sole thickness (sagittal, lateral and medial) using DR and magnetic resonance images. One observer repeated the measurements 3 times. Inter- and intraobserver correlation was assessed. Digital radiography and MRI measurements for the normal hoof wall and sole were established. Inter- and intraobserver pairwise Pearson’s correlation for DR (r>0.98) and MRI measurements (r>0.99) was excellent. Based on MRI, the less radiopaque layer on DR is comprised of the stratum lamellatum and stratum reticulare. Normal DR and MRI measurements for the hoof wall and sole were established. On DR images, the less radiopaque layer of the foot observed corresponds to the critical tissues injured in laminitis, the strata lamellatum and reticulare. These reference measurements may be used by the clinician to detect soft-tissue changes in the laminitic equine foot and provide a foundation for future research determining changes in these measurements in horses with laminitis.

Die Cochlea-Implantat (CI)-Forschung ist ständig bestrebt, CI-Elektroden weiterzuentwickeln sowie neue Implantattypen zu etablieren, um einen immer besseren Höreindruck bei den CI-Patienten zu erzeugen. Ein entscheidendes Ziel in diesem Zusammenhang ist es, chronische Entzündungsprozesse und fibrotische Gewebeproliferationen, die als Reaktion auf den implantierten Fremdkörper in der Cochlea auftreten können, zu minimieren. So können bindegewebige Einkapselungen des Implantates zu einer Erhöhung der Impedanzen an den Elektrodenkontakten und damit zu einer geringeren Spannbreite in der Dynamik, also dem Lautstärkebereich, führen. Weiterhin können die cochleäre Mechanik wie auch die Signaltransduktion zum Hörnerv durch fibrotische Gewebereaktionen beeinträchtigt werden. Darüber hinaus können chronisch inflammatorische Prozesse eine fortschreitende Zerstörung sensorineuraler Strukturen in der Cochlea verursachen. Es gibt verschiedene Ansätze, diesen implantationsbedingten chronischen Entzündungsprozessen und fibrotischen Proliferationen entgegenzuwirken. Eine erfolgversprechende Methode zielt darauf ab, die chemische Zusammensetzung der Materialien auf der Oberfläche des Implantates zu modifizieren. Poly[bis(trifluoroethoxy)phosphazen] (PTFEP) ist ein hoch biokompatibles, anorganisches Polymer, das bereits erfolgreich als passivierende Oberflächenbeschichtung von kardiovaskulären Stents eingesetzt wird. In dieser in-vivo Studie am Meerschweinchen-Modell wurde PTFEP erstmals als Oberflächenbeschichtung von CIs untersucht. Impedanzuntersuchungen und ABR-Hörmessungen implantierter Meerschweinchen (mit oder ohne Beschichtung) wurden zu verschiedenen Zeitpunkten nach der Implantation (Woche 1, 2, 5, 9, 12 und 16) durchgeführt. Ferner wurde 16 Wochen nach der Implantation eine abschließende histologische Untersuchung der Cochleae einschließlich einer immunhistologischen Analyse von degenerierten Spiralganglienzellen (SGN) vorgenommen. Obwohl die Hörmessungen zwar in keinem Frequenzbereich einen signifikanten Unterschied zwischen beiden Gruppen ergaben, zeigten Meerschweinchen mit beschichteten Implantaten dennoch ein zumindest tendenziell besseres Hörvermögen in den hohen Frequenzbereichen (4-32 kHz). Die histologische Untersuchung zeigte bei Cochleae mit beschichteten Implantaten zudem eine signifikant geringere lymphoplasmatische Infiltration der basalen Windung (p = 0,012). Ein überraschendes und zugleich positives Ergebnis war außerdem, dass der SGN-Verlust in der basalen Windung bei beschichteten Implantaten gegenüber unbeschichteten Implantaten nach 16 Wochen signifikant geringer war (p = 0,003). Trotz dieser vielversprechenden Resultate sind dennoch weiterführende Untersuchungen nötig, da bei beiden Implantat-Typen kein signifikanter Unterschied hinsichtlich der Anzahl an Fremdkörperriesenzellen (p = 0,800) zu erkennen war. Weiterhin konnten keine signifikanten Unterschiede hinsichtlich der bindegewebigen Proliferationen (p = 0,382) und der Knochenneubildung (p = 0,239) beobachtet werden. Es ist daher davon auszugehen, dass eine PTFEP-Beschichtung keinen direkten Einfluss auf die bindegewebigen Proliferationen um das Implantat hatte und eine Fremdkörperreaktion auf das Implantat in der Cochlea nicht unterdrücken konnte. Ein unerwartetes Ergebnis ergaben auch die Impedanzmessungen. Die Ausgangsmessungen an Tag 0 unmittelbar nach der Implantation zeigten bei beschichteten Implantaten signifikant geringere Impedanzwerte im Vergleich zu unbeschichteten Implantaten (basaler Elektrodenkontakt: p = 0,019, apikaler Elektrodenkontakt: p = 0,024). Ab dem nächsten Messzeitpunkt Woche 1 bis zum Messzeitpunkt Woche 12 jedoch waren die Impedanzen bei den PTFEP-beschichteten Implantaten signifikant größer statt, wie zu erwarten war, kleiner. Die Ursachen für dieses überraschende Ergebnis konnten in dieser Untersuchung allerdings nicht hinreichend geklärt werden und müssen in Folgestudien weiter evaluiert werden. Die Studie konnte zeigen, dass die hoch biokompatible Beschichtung möglicherweise einer mononukleären Infiltration in der basalen Windung und einer Degeneration von Spiralganglienzellen nach der Implantation entgegenwirkt. Diese passive Beschichtung scheint daher ein vielversprechender Ansatz zur Verbesserung künftiger Implantate zu sein, möglicherweise in Kombination mit anti-inflammatorischen, pharmakologisch aktiven Substanzen, wie beispielsweise Glukokortikoiden. Dennoch wird es notwendig sein, weitere Untersuchung durchzuführen, da andere Parameter in der histologischen Untersuchung sowie die Hörmessungen keinen signifikanten Unterschied zwischen beschichteten und unbeschichteten Implantaten ergaben. Auch führten die Impedanzmessungen zu unerwarteten Ergebnissen und bedürfen einer Evaluation in weiteren Untersuchungen.

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Epigenetic programming facilitates the adaptation of an organism to changes in the environment through lasting alterations in gene expression that underlie certain physical and behavioral phenotypes. Exposure to adverse events in early postnatal life is known to increase the risk for stress-related psychiatric disorders later on. Our previous studies showed that early-life stress (ELS) in mice caused by periodic infant-mother separation (MS) leads to increased hyperactivity of the HPA axis, reduced glucocorticoid feedback inhibition, and depressive-like behavior. Moreover, our work revealed ELS-induced hypomethylation of the arginine vasopressin (Avp) gene enhancer and pro-opiomelanocortin (Pomc) promoter. The aim of the study was to investigate whether ELS can also lead to epigenetic programming of the mouse glucocorticoid receptor (GR, Nr3c1). GR is a major feedback regulator of the hypothalamic-pituitary adrenal (HPA) stress axis and its expression is regulated by multiple promoters associated with its5’ untranslated first exons. Given the fact that the mouse GR promoter was only partly characterized, we aimed to determine its genomic structure. In addition, tissue distribution and absolute quantification of newly identified alternative first exon transcripts were analysed. Although most of the first exon transcripts were found to be widely expressed, some of them are shown to be differentially regulated by growth factor- and depolarization-induced signaling. In the present work we show also that mice with a history of maternal separation display up-regulated GR mRNA levels. This observation was confined to Crh-producing neurons in the hypothalamic paraventricular nucleus (PVN), which are principal effectors of the stress response. Moreover, elevated levels of GR are shown to be responsible for stronger induction of its downstream target genes (Fkbp5, Sgk1, and DUSP1), which suggests an enhanced transcriptional activity of the GR in ELS mice. This effect is supported by a higher occupancy of the GR at the glucocorticoid response elements (GREs), following corticosterone injection (i.p.). Finally, we report here that an enhanced level of GR expression in ELS mice is accompanied by an increased methylation of specific CpG residues at the CpG island shore region of the GR promoter. These ELS-responsive CpGs comprise a DNA binding site for the transcriptional repressor Yin Yang 1 (YY1). Given the high homology of the mouse and human GR promoter, and the conservation of the YY1 binding site, we conducted a methylation analysis of the hGR CpG island shore region in peripheral tissues and post mortem brain samples. Our findings might serve as a basis for comparing the methylation patterns in tissues from control subjects and patients with stress-related brain disorders.