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Neural information processing in the Drosophila motion vision pathway
Get PDFDetecting the direction of image motion is an essential component of visual computation. An individual photoreceptor, however, does not explicitly represent the direction in which the image is shifting. Comparing neighboring photoreceptor signals over time is used to extract directional motion information from the photoreceptor array in the circuit downstream. To implement direction selectivity, two opposing models have been proposed. In both models, one input line is asymmetrically delayed compared to the other, followed by a non-linear interaction between the two input lines. The Hassenstein-Reichardt (HR) model proposes an enhancement in the preferred direction (PD): the preferred side signal is delayed and then amplified by multiplying it with the other input signal. In contrast, the Barlow-Levick (BL) detector proposes a null direction (ND) suppression, whereby the null side signal is delayed and the other input is divided by it. The motion information is computed in parallel ON and OFF pathways. T4 and T5 are the first direction-selective neurons found in the ON and in the OFF pathway, respectively. Four subtypes of T4 and T5 cells exist each responding selectively to one of the four cardinal directions: front-to-back, back-to-front, upwards, and downwards, respectively.
In the first manuscript, we found that both preferred direction enhancement and null direction suppression are implemented in the dendrites of all four subtypes of both T4 and T5 cells to compute the direction of motion. We, therefore, propose a hybrid model combining both PD enhancement on the preferred side and ND suppression on the null side. This combined strategy ensures a high degree of direction selectivity already at the first stage of calculating motion direction.
Further processing, in addition to synaptic mechanisms on the dendrites of T4 cells, can improve the direction selectivity of the T4 cells' output signals. Such processing might involve: 1.) transformation from voltage to calcium, and 2.) from calcium to neurotransmitter release. In the second manuscript, we used in vivo two-photon imaging of genetically encoded voltage and calcium indicators, Arclight and GCaMP6f respectively, to measure responses in Drosophila direction-selective T4 neurons. Comparison between Arclight and GCaMP6f signals revealed calcium signals to have a significantly higher direction selectivity compared to voltage signals. Using these recordings we built a model which transforms T4 voltage responses into calcium responses. The model reproduced experimentally measured calcium responses across different visual stimuli using various temporal filtering steps and a stationary non-linearity. These findings provided a mechanistic underpinning of the voltage-to-calcium transformation and showed how this processing step, in addition to synaptic mechanisms on the dendrites of T4 cells, enhances direction selectivity in the output signal of T4 neurons.
The two manuscripts included in this thesis are presented chronologically and were published in peer-reviewed journals
Validation and assimilation of Aeolus wind observations
Get PDFAlong with scientific and technological developments, the advancement of the Global Observing System (GOS) has been one of the most important factors contributing to the increase in numerical weather forecasting (NWP) skill in recent years. The initial conditions of a forecast are provided by data assimilation systems, combining the latest short-range forecast with a selection of atmospheric observations. One of the current major limitations is the lack of global wind profile observations, particularly in regions and for spatial scales where geostrophic mass-wind coupling is weak.
The European Space Agency's (ESA) Doppler Wind Lidar (DWL) satellite mission Aeolus provides a novel data set of wind profiles with quasi-global coverage intended to fill this gap in the GOS. This thesis aims to assess the impact of the Aeolus observations in NWP to demonstrate the potential value of such satellite-based DWL missions.
A crucial prerequisite for using meteorological observations in NWP data assimilation systems is the knowledge and characterization of their errors. Therefore, in the first part of this work, a validation study is conducted to investigate the quality of the Aeolus wind profiles. Comparisons with three independent reference data sets - collocated radiosonde observations as well as model equivalents of the global ICOsahedral Nonhydrostatic (ICON) model of the German Weather Service (DWD) and the Integrated Forecast System (IFS) model of the European Centre for Medium-Range Weather Forecasts (ECMWF) - enable a comprehensive estimation of the systematic and random errors of the Aeolus observations. In addition, the systematic errors are examined for their dependencies, and correction approaches that can be used in data assimilation systems as part of quality control are tested.
Discrepancies between the radiosonde and model-based validation results that occur in determining the random error are mainly due to differences in spatial and temporal representativeness. The representativeness error components can be estimated using high-resolution regional model simulations and thus can be taken into account in determining the Aeolus observational error. The results provide important information on the magnitude and vertical structure of the Aeolus Rayleigh and Mie wind error, which serves as the basis for the assigned observational error in the data assimilation.
The second part of this thesis examines how numerical weather forecasting benefits from the assimilation of the novel DWL observations from the Aeolus satellite. For this purpose, an Observing System Experiment (OSE) based on the operational global assimilation system of ICON at DWD with and without the assimilation of Aeolus observations is analyzed. Besides global impact statistics, regions and periods with particularly pronounced impact are investigated further to understand the underlying dynamics leading to the overall beneficial impact. The largest impact of assimilating Aeolus observations occurs in the 2-3 day wind and temperature forecast in the tropical upper troposphere and lower stratosphere and in the Southern Hemisphere. The influence of the Aeolus observations in the Northern Hemisphere is less pronounced but still relatively large compared to other observing systems. Furthermore, this thesis illustrates three examples of atmospheric phenomena that constitute dynamical scenarios for significant forecast error reduction: the change of the oscillatory phase of two large-scale tropical circulation systems - the quasi-biennial oscillation (QBO) and the El Niño–Southern Oscillation (ENSO) - and the interaction of tropical cyclones undergoing extratropical transition (ET) with the midlatitude waveguide. These indications of dynamical changes and processes related to the particularly high impact of Aeolus on NWP forecasts provide important information for the advancement of observing and NWP systems and will serve as the basis for future studies on opportunities to improve NWP forecasts by additional observations
Einfluss einer individuellen Kiefergelenksregistrierung auf die Rekonstruktion von okklusalen Oberflächen
Get PDFThe role of E47 in patients with endogenous glucocorticoid excess
Get PDFE47 ist ein Transkriptionsfaktor und wurde kürzlich als Modulator von Glukokortikoidrezeptor-Zielgenen identifiziert. Sein Verlust schützt Mäuse vor den nachteiligen metabolischen Auswirkungen von Glukokortikoiden. Patienten mit Cushing-Syndrom (CS) sind aufgrund eines Überschusses an endogenen Glukokortikoiden stark von verschiedenen metabolischen Komorbiditäten betroffen. In der vorliegenden Arbeit wurde die Rolle von E47 bei Patienten mit endogenem Glukokortikoid-Überschuss analysiert.
Wir führten eine retrospektive Kohortenstudie mit 120 Patientinnen mit CS (ACTH-abhängig = 79; ACTH-unabhängig = 41) und 26 gesunden weiblichen Kontrollen durch. Die E47 mRNA-Expression wurde zwischen verschiedenen CS-Untergruppen, bei floridem Cuhsing-Sydrom und in Remission nach der Operation sowie nach ACTH-Stimulation und Dexamethason-Suppressionstest bei den Kontrollen gemessen. Ebenso wurde die E47-Genexpression mit metabolischen Komorbiditäten bei CS korreliert.
Wir fanden heraus, dass die E47-Genexpression bei Patienten mit floridem CS (n = 29) im Vergleich zu Patienten in Remission (n = 91; p = 0.0474) signifikant niedriger war. Die E47-Genexpression war in der prä-chirurgischen Untergruppe der CS-Patienten im Vergleich zu den Patienten nach erfolgreicher Operation (n = 14; p = 0.0353) signifikant niedriger. Die Verabreichung von 1 mg Dexamethason bei gesunden Kontrollen zeigte keine Veränderungen in der E47 mRNA-Expression. Die Stimulation mit Synacthen© von Gesunden hingegen führte zu einer positiv signifikanten Abnahme der E47 mRNA-Expression nach 30 Minuten intravenöser Verabreichung im Vergleich zur Ausgangsmessung (p = 0.0015). Die E47-Genexpression korrelierte außerdem positiv mit den Messungen des Serum-Gesamtcholesterins (p = 0.0036), des LDL-Cholesterins (p = 0.0157) und des Verhältnisses von Taille zu Arm (p = 0.0138) in der Untergruppe der CS-Patienten in Remission.
Zusammenfassend beschreibt diese Arbeit, dass die E47 mRNA-Expression sowohl bei CS-Patienten als auch bei Kontrollen eine hohe Streuung aufwiesen. E47 scheint ein GC-abhängiges Gen zu sein, das bei einem endogenen GC-Überschuss herunterreguliert wird und möglicherweise darauf abzielt, die Nebenwirkungen von metabolischen Glukokortikoiden zu reduzieren.E47 is a transcription factor and has recently been identified as a modulator of glucocorticoid receptor target genes. Its loss protects mice from the adverse metabolic effects of glucocorticoids. Patients with Cushing's syndrome (CS) are severely affected by various metabolic comorbidities due to an excess of endogenous glucocorticoids associated with tumour formation.
The aim of this study was to analyse the role of E47 in patients with endogenous glucocorticoid excess. We performed a retrospective cohort study with 120 female patients with CS (ACTH-dependent = 79; ACTH-independent = 41) and 26 healthy female controls. E47 mRNA expression was measured in different CS subgroups, before and after successful surgery, and after ACTH stimulation and dexamethasone suppression test in controls. We also investigated the correlation between E47 gene expression and metabolic comorbidities in CS .
We found that E47 gene expression was significantly lower in patients with overt CS (n = 29) compared to patients in remission (n = 91; p = 0.0474). E47 gene expression significantly decreased in the pre-surgical subgroup of CS patients compared to their corresponding post-surgical samples (n= 14; p = 0.0353). Administration of 1 mg dexamethasone in healthy controls showed no changes in E47 mRNA expression. Stimulation with Synacthen© in healthy controls, however, resulted in a positive significant decrease in E47 mRNA expression after 30 minutes of intravenous administration compared to baseline measurements (p = 0.0015). E47 gene expression was positively correlated with serum total cholesterol (p = 0.0036), LDL cholesterol (p = 0.0157) measurements, and waist-to-arm ratio (p = 0.0138) in the subgroup of CS patients in remission.
Taken together, this thesis describes that E47 mRNA expression showed a high dispersion in both CS patients and controls. E47 appears to be a GC-dependent gene that is downregulated in the presence of endogenous GC excess and may aim to reduce the side effects of metabolic glucocorticoids
Einfluss des Reinigungsverfahrens auf die Materialeigenschaften von 3D-gedrucktem temporärem Zahnersatz
Get PDFThe effects of agricultural stressors and climate change on regime shifts in the dominance of aquatic phototrophic communities
Get PDFEnabling high-throughput image analysis with deep learning-based tools
Get PDFMicroscopes are a valuable tool in biological research, facilitating information gathering with different magnification scales, samples and markers in single-cell and whole-population studies. However, image acquisition and analysis are very time-consuming, so efficient solutions are needed for the required speed-up to allow high-throughput microscopy.
Throughout the work presented in this thesis, I developed new computational methods and software packages to facilitate high-throughput microscopy. My work comprised not only the development of these methods themselves but also their integration into the workflow of the lab, starting from automating the microscopy acquisition to deploying scalable analysis services and providing user-friendly local user interfaces.
The main focus of my thesis was YeastMate, a tool for automatic detection and segmentation of yeast cells and sub-type classification of their life-cycle transitions. Development of YeastMate was mainly driven by research on quality control mechanisms of the mitochondrial genome in S. cerevisiae, where yeast cells are imaged during their sexual and asexual reproduction life-cycle stages. YeastMate can automatically detect both single cells and life-cycle transitions, perform segmentation and enable pedigree analysis by determining origin and offspring cells. I developed a novel adaptation of the Mask R-CNN object detection model to integrate the classification of inter-cell connections into the usual detection and segmentation analysis pipelines.
Another part of my work focused on the automation of microscopes themselves using deep learning models to detect wings of D. melanogaster. A microscope was programmed to acquire large overview images and then to acquire detailed images at higher magnification on the detected coordinates of each wing. The implementation of this workflow replaced the process of manually imaging slides, usually taking hours to do so, with a fully automated, end-to-end solution