Quantum spin liquids are novel phases of matter whose physical properties cannot be captured within the conventional framework of phase transitions. These quantum states are characterized by excitations, called spinons, carrying a fractional value of the integer spin. A description based on a mean-field approximation leads to effective gauge theory. Due to this gauge freedom symmetry group operations act via projective symmetry group (PSG) representations, which can be used to classify quantum states beyond the conventional method. This introducing discussion is found in Chapters 2-6. A preceding PSG classification on the square lattice, which took spin rotational symmetry breaking terms into account, showed that the resulting mean-field states could exhibit topologically non-trivial spinon bands. In Chapter 7, only those el- ements of this Classification are studied, which lead to short-ranged mean-field models. The mutual effect of spinons and visons is scrutinized by adding static configurations of a background gauge field. Spinons and visons form composite ob- jects, which in the case of topological spinon bands, are described by Majorana zero modes. An exact mapping corroborates the relation to topological supercon- ductors and vortices. The effect of multiple visons is investigated, and a possible experimental signature is exposed. Chapter 8 explains how spinon mean-field theory can be used to derive a phe- nomenological effective model for the compound Ca 10 Cr 7 O 28 . A material that was recently proposed as a quantum spin liquid. This low-energy theory consists of spinon hopping processes. The underlying bilayer kagome structure can be simpli- fied to an effective honeycomb lattice. The dynamical spin structure factor is calcu- lated and compared to neutron scattering data. It is discussed how f -wave pairing of spinons can explain small deviations from a linear temperature dependency observed in heat capacity measurements at the low temperatures. This pairing mechanism breaks the U (1) invariance group of the pure hopping model and renders a coherent picture of Ca 10 Cr 7 O 28 being a Z 2 quantum spin liquid. Chapter 9 carries out a PSG classification for the simple-, body centered-, and face centered cubic lattices. Despite a large number of possible PSG representations, only very few describe short-ranged mean-field states. These mean-field models are constructed up to third neighbor couplings and calculated in a self-consistent manner. It is found that the energy is lower for non-trivial sign patterns induced by non-trivial representations of the symmetry generators. Higher neighbor extensions, including pairing terms, yield lower mean-field ground state energies compared to extensions with only hopping terms. For the fcc lattice, a first neighbor state could be identified, which exhibits symmetry protected zero-energy modes.Weniger anzeigen
Die aus der Humanmedizin bekannte BRAF-Variante V595E wurde erstmals 2015 von MOCHIZUKI et al. (2015a) in Übergangszellkarzinomen (ÜZCa) und Prostatakarzinomen (PCa) des Hundes nachgewiesen. Ziele der vorliegenden Arbeit waren, zum ersten Mal auch für zytologische Ausstriche von Harnsedimenten und Feinnadelaspiraten ein Nachweisverfahren zu etablieren, die diagnostische Relevanz der BRAF-Mutation in den beiden genannten kaninen Neoplasien erstmals auch in der europäischen Hundepopulation zu untersuchen sowie den Zusammenhang zwischen der BRAF-Mutation, den histologischen Befunden und der immunhistologischen COX-2-Expression im ÜZCa zu erforschen. Dazu wurden aus den Routineeinsendungen an die Firma LABOKLIN GmbH & Co. KG und an das Institut für Tierpathologie der Universität Berlin in den Studien 1 und 2 insgesamt 101 Bioptate (Studie 1: n = 36; Studie 2: n = 65), 48 Urinproben und/oder 31 zytologische Ausstriche der Harnblase von Hunden mit ÜZCa (n = 98; Studie 1: n = 33; Studie 2: n = 65), Zystitis (Studie 1: n = 23), Harnblasenpolypen (Studie 1: n = 7) oder ohne pathologische Veränderungen (Studie 1: n = 3) histologisch, immunhistologisch und molekulargenetisch untersucht. In Studie 3 wurden 70 Biopsien und 17 zytologische Ausstriche der Prostata mit PCa (n = 46, davon zytologisch: n = 11), benigner Prostatahyperplasie (n = 22), Prostatitis (n = 14), Plattenepithelmetaplasie (n = 2) und Atrophie der Prostata (n = 3) ebenfalls aus den Routineeinsendungen an die Firma LABOKLIN GmbH & Co. KG histologisch und molekulargenetisch untersucht. Das Verfahren des Nachweises der BRAF-Mutation konnte erfolgreich für zytologische Ausstriche etabliert werden (Studie 1: ÜZCa, Studie 3: PCa) und die Mutation auch in den ÜZCa und PCa der europäischen Hundepopulation nachgewiesen werden (Studien 1 und 2 (ÜZCa): Terrier: 88 bzw. 73 %, Nicht-Terrier: 65 bzw. 36 %; Studie 3 (PCa): 61 %). Da in keiner der untersuchten Proben mit den genannten anderen Erkrankungen die BRAF-Mutation nachgewiesen werden konnte, handelt es sich um ein hochspezifisches (100 %) Verfahren, das eine sehr gute Ergänzung in der Diagnostik beider Neoplasien des Hundes darstellt. Durch die BRAF-Mutation bedingte PCa wiesen einen signifikant höheren Gleason-Score (schlechter differenziertes vorherrschendes Wachstumsmuster) auf als PCa ohne diese Mutation. Im Gegensatz dazu konnte in Studie 2 kein Zusammenhang zwischen der BRAF-Mutation und dem histologischen Grad (low- vs. high-grade) der ÜZCa gezeigt werden. Immunhistologisch konnte im kaninen ÜZCa ebenfalls kein signifikanter Zusammenhang zwischen dem histologischen Grad und der Intensität der COX-2-Expression festgestellt werden. Bei durch die BRAF-Mutation verursachten ÜZCa von Hunden der Nicht-Terrier-Rassen konnte jedoch eine höhere Intensität der COX-2-Expression detektiert werden als in ÜZCa ohne diese Mutation. Dieser Zusammenhang ließ sich aber nicht auf ÜZCa von Terriern übertragen. Letztere zeigten unabhängig vom Vorliegen der BRAF-Mutation eine stärkere COX-2- Expression als ÜZCa anderer Rassen. Die klinische, therapeutische und prognostische Relevanz dieser Befunde ist zum jetzigen Zeitpunkt noch nicht absehbar. Der Nachweis der BRAF-Mutation stellt in der Tiermedizin jedoch ein innovatives molekulargenetisches Verfahren dar, welches in Zukunft eine personalisierte Therapie von kaninen ÜZCa und PCa mit COX- und RAF-Inhibitoren ermöglichen könnte. Studien zum Einsatz von RAF-Inhibitoren in der Behandlung BRAF-positiver Neoplasien des Hundes sollten deshalb unbedingt forciert werden.Weniger anzeigen
This thesis presents novel local trajectory planning methods to provide a safe, time optimal, and comfortable passenger ride. Trajectory planning is an essential part of autonomous driving systems, which has been extensively studied for robots during the past few decades. Providing passenger comfort, especially when working within a highly dynamic environment, makes the trajectory planning problem more challenging. Based on the autonomous car situations, three different trajectory planning methods are proposed. The first method is a reactive trajectory planning which works in structured road maps with reference paths. The trajectory speed points are limited based on the road curvature, the traffic rules, and the distances to obstacles. A new algorithm is developed to smooth the speed profile considering the jerk and acceleration constraints. The jerk constraint is defined to provide passengers with a comfortable ride. The acceleration is limited based on the vehicle model and passenger comfort. The vehicle model is determined using the system identification. This approach is suitable for driving in urban areas with dynamic environments in which the obstacle speed changes frequently and the ego car trajectory must react to obstacles while avoiding instant braking or accelerating. In the second trajectory planning approach, a new artificial force vector in three dimensions (longitudinal and lateral position, and speed) allows the autonomous car to follow aspecific path. The vector field is created based on distance from the path and the car speed. It is locally modified by presence of obstacles. By switching between two different vector fields, the vehicle can change a lane or follow another path. The vector field approach is suitable for complicated paths with low traffic such as parking lots. The third trajectory planning approach, Flexible Unit A∗ (FU-A∗), is a new modified tree-based search algorithm in 3-dimensional space (longitudinal and lateral position, and time) in which lane-changing decision is also considered. The energy consumption, time duration, and displacement are integrated in the cost function of the algorithm. This combining of decision-making for lane-changing and following the reference path is one of this thesis’ innovations. The feasibility and reliability of the designed methods are validated through several simulations and implementation on Freie University autonomous cars.Weniger anzeigen
Governing Poor Spaces. Homeless encampments and the new management of housing insecurity in the US The financial and urban crisis of 2008 highlighted once again the sustained problem of homelessness in the US. The iconic image of housing crisis and insufficient welfare provision are the growing homeless encampments or tent cities which pose a significant problem for local governance. Focusing on the local responses to homeless encampments this dissertation analyzes the transformation of homeless management in the neoliberal welfare state, and inquires how spatial practices of informal survival conflict but also resonate with new forms of managing the non-propertied in propertied space. In contrast to the dominant strategies of criminalizing homeless survival, several cities in the US have legalized camps and established them as alternative shelter spaces. Such regulatory experiments are interpreted in ambiguous ways: where some identify this as pragmatic and humane policy to expand capacity of shelter at low cost, others interpret it as progressive policy that recognizes the informal self-help as valuable resource, some recognize these self-help communities as act of collective empowerment of the non-propertied to claim a first step to the human right to housing, others fear the emergence of new substandard shelter that fit the neoliberal imperatives of austerity. This dissertation responds to the call of critical geographers for more nuanced analysis of homeless management and the local state by analyzing how poverty is governed through space. It re-visits central debates on the governance of urban marginality, highlights explanatory strengths and weaknesses, and conceptualizes homeless management as specific project of poverty governance. Drawing on theories of hegemony, homeless management is understood as political strategy that is not limited to manage the homeless populations with more or less coercion or care, but aims to neutralize the nexus of homelessness and housing insecurity in order to stabilize the hegemony of propertied citizenship. The struggle over the legalization of homeless camps presents a sharp lens to examine the current re-calibration of state governance of urban marginality, i.e. the current mix of penal, welfare and informal strategies that are used to manage (and neutralize) homelessness. A critical and relational policy analysis is applied to examine comparatively the process of policy-making in the local state: addressing the roles of homeless advocates and activists, charitable and non-profit service providers, and local government actors in co-shaping the process of regulatory experimentation. Highlighting path-dependent corridors of contingency the three empirical cases of Seattle, Fresno and Ontario show how the legalization of homeless camps emerges as result of multiple distinct crises of homeless management. The legalized camps depict new welfare state spaces with different socio-spatial compromises between state control and homeless claims for a right to shelter and self-determination. Specifying how the neoliberal and paternalist components of homeless management are re-worked and searching for a paradigmatic case, the comparison shows why self-governed camps are more likely to stabilize local hegemony than top-down governed camps. To contextualize the case studies, the last chapter discusses why such solutions were viable in some cities but remain marginal. Re-questioning the neoliberal policy fit of legalized homeless camps as cheap and self-managed shelter extension of homeless relief, the case studies allow to trace the emergence of a new national hegemonic project to determine local policy-making: focused on “ending homelessness” through housing first. Despite its failures evidenced by growing numbers of unsheltered homeless, the promise for “ending homelessness” is successful in addressing the unresolved crises of homeless management in a new way. But in the name of an ideal to come, local compromises that respond to immediate shelter need are marginalized. Analyzing local struggles for necessary and adequate shelter and housing in relation to the national policy developments this dissertation explains how in the current conjuncture homelessness is dealt with and structural housing insecurity is neutralized again. While the political terrain for local compromises contracts as claims for recognizing spaces of survival with more decency through autonomy are marginalized again, the work concludes by pointing to a new perspective developed by movements: they continue to challenge their neutralizing by claiming space through a legal right for survival.Weniger anzeigen
The focus of this thesis is the investigation of the spatial configuration and formation mechanisms of a type of terrain known as araneiform terrain or "spiders" found in the south polar regions of Mars. Seasonal sublimation and condensation of CO2 at the poles are an essential part of cycles of global volatiles (CO2 and H2O) and dust, e.g., up to 25% of the Martian atmosphere's CO2 interacts annually with the polar surfaces. The seasonal CO2 ice condenses on the poles of Mars each autumn/winter; it can form translucent slab ice which is transparent in the visible light and opaque in the infrared. This physical property allows basal sublimation of the seasonal CO2 ice under insolation in spring. The resulting CO2 accumulation and jetting leads to transitional features such as dark spots/fans and radial or dendritic troughs known as araneiform terrain (“spiders”). Thus, spider formation is linked to the global CO2 cycle and the seasonal evolution of the Martian poles which are sensitive to the Mars climate. It is one of the most active current erosive processes on Mars which involves mobilization of material jetted from the substrate relocating a greater mass of dust than either dust storms or the cumulative effect of dust devils. Observations at seven study regions in this work reveal diverse morphologies of spider forms, which suggest variability of araneiform formation processes. Based on my observations, a spider formation model is developed to explain the formation of spiders and their growth processes. I consider the migration of pressurized CO2 through the porous substrate towards cracks in the overlying CO2 ice layer, and the effect of the substrate's cohesive strength on the development of spider troughs. Thus, substrate properties (permeability, porosity, and cohesion) are significant parameters controlling the mechanism of spider growth. The major advantage of this model is that it explains the mechanism of the growth of central pits and radiating troughs, and parameters (e.g., trough length) of their morphologies, which have not been considered before. This model suggests that spider troughs are created from the developments of random protrusions of initial degradational forms. My trough orientation mappings and constructed rose diagrams are consistent with this theory showing that spider troughs do not have preferred orientations and appear randomly distributed. Due to rate differences between local pressure accumulation and lateral gas migration, the model reveals an inhibited zone existing around a newly formed spider that diminishes pressure accumulation preventing another CO2 jet. This suggests the spatial distributions of spiders to be non–random. Spatial randomness analysis of the seven spider populations confirms this non–randomness and indicates a strong regional variation of spider average spacings. Regional differences in substrate properties (permeability, porosity, and cohesion) are the likely causes of the regional variation. Other parameters, such as seasonal CO2 ice thickness and grain size, local climate, obliquity, and latitude, also influence spider formation and spatial configurations. This research improves the understanding of how CO2 jetting and subsequent spider formation shaped and modified the south polar surface of Mars which may actively occur at the present time, and how volatiles (CO2 and water) and dust play their roles in the polar processes and Mars global circulation. Furthermore, it provides insight into the recent climate conditions of Mars.Weniger anzeigen
By means of modeling and mathematical analysis, this thesis investigates negative phototaxis of Euglena gracilis and resulting bioconvection patterns under stationary or periodic illumination. This thesis provides a new biological hypothesis about the mechanism of negative phototaxis of Euglena gracilis and gives an account of the failure of pattern formation under rapidly periodic illumination which was reported by an experimentalist. An existing model of patterns under stationary illumination is extended to a new model of patterns not only under stationary illumination but also under rapidly periodic illumination. The new model has Turing instability for coefficients corresponding to stationary illumination, and loses Turing instability if coefficients are replaced by those corresponding to rapidly periodic illumination. The failure of pattern formation under rapidly periodic illumination can be interpreted as the loss of Turing instability.Weniger anzeigen
Mit Foucault und Heidegger über ethos nachzudenken, kann grundlegende Impulse für die Beschäftigung mit der Ethik geben. Dabei ist ethos als „Seinsweise“ (Foucault) und als „Aufenthaltsort“ (Heidegger) zu bedenken und damit dessen jeweils signifikanter Bezug zum Dasein in der Welt aufzuzeigen. So wird deutlich: Dasein konstituiert und verortet sich im Denken, Reden und Handeln in praktischer und zugleich inhärent reflexiver Art und ist damit von sich aus grundlegend als ethisch zu begreifen. Das Dasein oder ethos ist somit als Ort der Begegnung zu verstehen und umfasst das Selbst, die anderen Mitmenschen und die Umwelt (mit ihren Lebewesen) als dessen ethische Dimensionen oder Achsen der eigenen Lebenspraxis und -erfahrung. Statt diese „nur“ ontologisch zu betrachten, geht es mir um die Grundformen ethischer Praxis, durch die sie ausgeprägt werden. Diese Grundformen beruhen auf der Freiheit sich zu seinem Verhalten verhalten, sein Handeln reflektieren und darin eine gewisse Haltung an den Tag legen zu können. In diesem Zusammenhang zeigen sich drei Grundformen ethischer Praxis, wie ich sie mit Heidegger und Foucault verstehe, die auf die Transformation und Transzendenz des eigenen Daseins gerichtet sind. Diese drei Grundformen ethischer Praxis können als Kritik, Sorge und Gelassenheit begriffen werden, die wiewohl dem Dasein gewissermaßen selbst eigen, zugleich eine praktische Einübung verlangen.Weniger anzeigen
The lunar and mercurian cratering records provide valuable information about the late accretion history of the inner Solar System. However, our understanding of the origin, rate, and timing of the impacting projectiles is far from complete. Different late accretion models including single and multiple impactor populations may explain the early lunar bombardment history. The single impactor population model explains the exponential decay of impactors over time (e.g., Neukum, 1983; Neukum & Ivanov, 1994; Hartmann, 1995), and the Late Heavy Bombardment (LHB) or lunar cataclysm model suggests different impactor populations with a rapidly increasing impact flux at 3.9 Gyr (Ryder, 1990, 2002). The primarily aim of this work is to test various accretion models and improve the lunar production function (PF) by re-evaluating its shape to infer potential impactor populations. To learn more about these projectiles, we can examine crater size-frequency distributions (CSFDs) on the Moon and Mercury. This PhD thesis re-investigates the crater populations of large (D ≥ 300 km) lunar and mercurian basins using the buffered crater counting (BCC) and buffered non-sparseness correction (BNSC) techniques. BSNC is a novel CSFD technique, which takes crater obliteration on highly cratered surfaces into account, thus providing more accurate measurements for the frequencies of smaller crater sizes. The BNSC-corrected CSFDs of individual basins, particularly at smaller crater diameters increase compared to the crater frequencies derived from the BCC technique alone. Furthermore, a new basin catalogue of 94 basins has been produced on Mercury, 80 of which have been classified as certain or probable, 1.7× times more than previously recognized. However, this number of basins has been estimated to represent roughly half of the expected basin record, where basins older than Borealis have been obscured by different processes (e.g., higher impact melt production, volcanism, subsequent impacts, and viscoelastic relaxation of basins). Consequently, if the Neukum (1983) and Neukum et al. (2001a) theories are correct that the impactor population in the inner Solar System did not change over time, one could expect that the summed CSFDs of basins in different time periods maintain a single shape following the lunar PF. Contrary to previous studies, the shape of summed CSFDs of Pre-Nectarian (excluding South Pole-Aitken Basin), Nectarian (including Nectaris) and Imbrian (including Imbrium) basins show no statistically significant differences, and thus provide no evidence for a change of impactor population bombarded the lunar surface. Similarly, the results on the shape of summed CSFDs of Pre-Tolstojan and Tolstojan basins on Mercury are consistent with the lunar study. The secondary aim is to find potential key landing sites for future human and robotic exploration missions with sample return capability on the lunar surface, which could target key sampling locations in order to verify the preferred late accretion model and refine the lunar chronology model, and thus, the absolute model ages (AMA) of different geologic units on the Moon and other terrestrial planets. In order to do so, this dissertation focus on the exploration of the South Pole-Aitken basin with the main focus on the south polar region of the Moon, a region that has not been visited by any human missions, yet exhibits a multitude of scientifically important locations – the investigation of which address long-standing questions in lunar research. The findings show that a human-assisted robotic mission to the South Pole-Aitken basin, can address all seven US National Research Council (2007) lunar science concepts, and would be a valuable resource to reveal the early history and evolution of the Solar System.Weniger anzeigen
Introduction: Community-acquired pneumonia (CAP) promotes dysregulation of the innate immune system and disruption of the endo-epithelial barrier function, leading to acute lung injury and edema formation. It represents a significant health burden worldwide with high mortality rates despite adequate antibiotic treatment. Streptococcus pneumoniae (S.pn.) is the predominant pathogen causing CAP. Upon S.pn. infection, neutrophils infiltrate and accumulate in the lungs, aiming at bacterial clearance. Neutrophil extracellular traps (NETs) are produced by the infiltrating neutrophils and may contribute to an enhanced inflammation of the tissue. This study investigates if NETs are also released after infection with S.pn. and if these structures contribute to the pneumonia-related tissue damage. It was previously demonstrated that the hormone-peptide adrenomedullin (ADM) protects mice against S.pn.-induced lung epithelial barrier disruption, pulmonary edema formation and extra-pulmonary organ damage. Here, it is further proposed that ADM protects against barrier failure by affecting the process of NET formation. Methods: A murine model for severe pneumococcal pneumonia was assessed to clarify the role of NETs in the disease. For this purpose, we evaluated different strategies aiming at NET degradation or inhibition of the process of NETosis, with DNase or PAD4 inhibition, respectively. Moreover, we targeted histones, the main cytotoxic component of NETs, with polysialic acid. The underlying mechanistic of ADM interference in NET formation were evaluated in vitro. Results: Neutrophils accumulate in the lungs and release NETs after infection with S.pn. NET degradation with DNase attenuated S.pn.-induced lung permeability. Targeting NETs and NETs-related components could reduce the inflammation in the lungs and was beneficial in improving the animal clinical outcome. ADM treatment led to a significant reduction in NET release, suggesting a direct effect of ADM on this process. In vitro, ADM suppressed NET production from activated neutrophils through a mechanism that involves receptor ligation, cAMP production, inhibition of ERK phosphorylation and ROS reduction. Conclusions: The results indicate that NETs have a deleterious role in the pathology of pneumococcal pneumonia and its inhibition may be beneficial for the disease outcome. ADM was shown to have beneficial properties apart from the stabilization of the endo-epithelial barrier, also by inhibiting NET production.Weniger anzeigen
Die Frühe Neuzeit gilt als eine Epoche der Kriegsverdichtung, in der verschiedene Faktoren, insbesondere aber die Prozesse der Herausbildung moderner Territorialstaaten zu einer signifikanten Steigerung der militärischen Auseinandersetzungen in Europa führten. Scheinbar analog zu dieser politisch-militärischen Situation ist seit dem Ende des 15. Jahrhunderts eine auffällige Zunahme der bildlichen Darstellungen von Schlachten zu beobachten, sowohl in den "hohen" Medien der Malerei, Skulptur und Tapisserie als auch im "niederen" Medium der Druckgraphik. Neben berühmten historischen Kriegsereignissen der Antike und des Mittelalters, mit denen auf zeitgenössische Geschehnisse Bezug genommen wird, werden nun auch in bisher nicht gekanntem Maße zeitgenössische Schlachten und Kriegshandlungen bildwürdig. Die Studie widmet sich dieser spezifischen Bildgattung und geht erstmals eingehender ihrer Entwicklung sowie ihren spezifischen Ausprägungen anhand ausgewählter Beispiele von den Schweizer Bilderchroniken über die Bilder der Schlachten Kaiser Maximilians I. bis hin zu Kriegsdarstellungen der Zeit Karls V. nach.Weniger anzeigen
In the present thesis, the step efficient synthesis of 3,4-dioxygenated quinolinones is described. Initially, step efficient syntheses of other natural products were analyzed by using a color-coded flow chart presentation. Thus, particularly powerful strategies were identified. These included disconnection in equally sized and complex substructures, avoidance of non-strategic redox- and functional group interconversions, as well as the usage of functional group tolerant transformations capable of forging multiple bonds in a single step. By applying these principles to the natural product class of 3,4-dioxygenated quinolinones, an aryne insertion into an unsymmetric imide followed by a diastereoselective aldol reaction was recognized.The target was thus built up from two equally sized molecules whilst the aryne insertion yielded two new carbon – -bonds in a single step. When performed in continuous flow, the reaction proceeded within minutes, while lower yields and longer reaction times were observed in batch. Furthermore, both aryne and imide could easily be varied so that a multitude of differently substituted 3,4-dioxygenated quinolinones were synthesized. In total, nine natural products, including (±)-peniprequinolone, (±)-aflaquinolones E and F, (±)-6-deoxyaflaquinolone E, (±)-quinolinones A and B, (±)-aniduquinolone C and yaequinolones J1 and J2, were synthesized in one to three steps.Weniger anzeigen
This thesis deals with two different topics from the field of polytope theory. In the first part we are concerned with the sets of f-vectors and flag vectors of polytopes. A new result is the complete description of the projection of the set of flag vectors of 4-dimensional polytopes onto the entries f0, the number of vertices, and f03, the number of vertex-facet incidences. Further new results are the descriptions of the set of all pairs of vertex and facet numbers of d-dimensional polytopes. In addition, we develop the concept of semi-algebraic sets of lattice points. This concept gives us a way of describing the “complexity” of the sets of f-vectors. We consider a number of different f-vector sets and find that these can for the most part be described as the set of all lattice points in a semi-algebraic set. Our main results in this chapter are two theorems that say that two particular f-vector sets cannot be described as the set of all lattice points in a semi-algebraic set. These sets are the set of the number of all edges and 2-dimensional faces of 4-dimensional polytopes, and the set of all f-vectors of d-dimensional polytopes, with d greater than or equal to 6. The second part focuses on Ehrhart theory of lattice polytopes, in particular the h∗-vectors of alcoved polytopes. The work in this part is motivated by the conjectured unimodality of the h∗-vectors of alcoved polytopes. First, the necessary concepts from Ehrhart theory and Stanley-Reisner theory are explained, and some unimodality conjectures are presented. The first main result in this part gives a condition under which alcoved polytopes have unimodal h∗-vectors: All alcoved polytopes with interior lattice points whose facets have lattice distance 1 to the interior lattice points have unimodal h∗-vectors. The second main result in this part gives a bound for how far off alcoved polytopes can be from this restriction. The theorem states that the facets of d-dimensional alcoved polytopes with interior lattice points have at most lattice distance d − 1 to the interior lattice points.Weniger anzeigen
Patients of Alzheimer’s Disease (AD) showed reduced levels of the actin-binding protein Drebrin in their neurons. The here presented work was set out to analyse the interaction between Drebrin and the disease-associated peptide Amyloid-β. To analyse the interaction in vivo two novel models were designed, employing the nematode C. elegans. The Amyloid-β pathology was modelled by overexpressing the disease causing peptide pan-neuronally and employing a genetic sub-stoichiometric labelling method to be able to follow the aggregation in vivo and in situ in a non-invasive manner. A second model, expressing human Drebrin pan-neuronally was generated to analyse Drebrin stability, localization and phosphorylation as well as analysing the effect of Drebrin overexpression on the nematodes’ vitality and fitness. The third project combined both generated models to obtain a genetic cross expressing Aβ(1-42) and Drebrin simultaneously. This model was sought to study the interaction between Aβ(1-42) and Drebrin. I could show, that Aβ(1-42) aggregates with the progression of ageing and exhibits multiple disease phenotypes that can be correlated to observations obtained in murine neurons as well as observations of AD patients’ brain tissues. Furthermore, I observed, that a distinct subset of head neurons of the anterior ganglion, the IL2 neurons, exhibits the first aggregates and that a cell-type specific suppression of Aβ(1-42) in IL2 neurons could delay the disease onset. Drebrin was observed to be regulated by phosphorylation at Serine-647 by Ataxia telangiectasia mutated kinase and render nematodes more resistant towards chronic oxidative stress. The genetic cross of Aβ(1-42) and Drebrin unravelled that overexpression of Drebrin can ameliorate Aβ(1-42) aggregation and toxicity and that this beneficial effect is dependent on phosphorylation of Drebrin-S647.Weniger anzeigen
The fly eye contains different subtypes of unit eyes (ommatidia) with molecularly and morphologically specialized photoreceptors for comparing either between different wavelengths (color vision) or between different angles of the linearly polarized skylight (polarization vision). However, microcircuit differences between those parts of the columnar medulla neuropil computing color versus polarization remain largely unknown. There is virtually nothing known about the circuit elements immediately downstream of polarization-sensitive photoreceptors in the ‘dorsal rim area’ (DRA). In this work, I described the cellular and synaptic architecture of medulla columns that receive skylight polarization input from DRA photoreceptors. I showed that only in the DRA region, R7 and R8 photoreceptors resemble each other by targeting their axons to the same medulla layer. However, within this layer DRA R7 and R8 connect to morphologically distinct Dm target cells (called Dm-DRA1 and Dm-DRA2, respectively). Both Dm-DRA cell types are modality-specific by avoiding contact with color-sensitive photoreceptors. Using the genetic toolbox of Drosophila such as activity-dependent GFP-reconstitution across synaptic partners (GRASP) and the genetically inducible trans-synaptic tracer ‘trans-Tango’, I confirmed that Dm-DRA1 and Dm-DRA2 are the specific post-synaptic targets of DRA.R7 or DRA.R8, respectively. Neither Dm-DRAs overlap with the main synaptic targets of color-sensitive R7 cells (called Dm8 cells), revealing for the first time that skylight polarization is processed by separate modality-specific circuits in the early visual system. These modality-specific differences are not limited only Dm-DRA cells. I described modality-specific cellular and synaptic specializations in other optic lobe cell types in the DRA region of the medulla: the dendritic arbors of certain cell types (neuromodulatory cells and visual projection neurons) specifically avoid the DRA region. Furthermore, Transmedullary (Tm) cells that are post-synaptic to color-sensitive photoreceptors showed modality-specific differences in connectivity or were absent from the DRA. Finally, I contributed a study describing the cellular organization of the ‘anterior visual pathway’ that carries skylight information from the eye to the central brain. In this study, I showed that an optic glomerulus called the anterior optic tubercle (AOTU) receives direct information via different classes of medulla-to-tubercle (MeTu) neurons, terminating in different subdomains of the AOTU. Finally, we hypothesize that different classes of MeTu cells carry different types of skylight information to the central brain via parallel pathways.Weniger anzeigen
In this thesis, a series of novel fluorinated ligands and corresponding metal complexes is presented. All compounds were spectroscopically and/or crystallographically characterized. The synthesis of a series of differently halogenated S,N,S-tridentate thiosemicarbazone ligands and their Re(V), Tc(V), Au(III) and In(III) complexes is described. The fluorination reduces the stability of the free ligands against hydrolysis but does not influence significantly the structure and stability of the Re, Tc and Au complexes. On the contrary, the structures and properties of the In(III) complexes are affected by fluorination. Some of the compounds were investigated regarding to their biological activity against Trypanosoma cruzi, a parasite responsible for a tropical disease, known as Chagas disease. Subsequently, the synthesis of Re(I) and Tc(I) complexes with fluorinated and non-fluorinated meta- terphenyl isocyanides is described. Reactions of [Re(CO)5Br] and (NBu4)[Tc2(CO)6(μ-Cl)3] with the encumbering isocyanides give stable complexes with a high degree of steric protection, which are suitable starting materials for the formation of highly-reduced and low-coordinated metal species. The reaction of the Re(I) and Tc(I) isocyanide complexes with different reducing agents is reported, leading to defined products containing persistent monomeric Re(0) complexes or rhenium in a negative formal oxidation state. Moreover, the first known complex with Tc in the formal –1 oxidation state was characterized with NMR spectroscopy.Weniger anzeigen
The main purpose of this dissertation is to examine how inter-firm relationships are formed and maintained to improve relationship performance. Much of the research on inter-organizational relationships has been conducted by marketing channel researchers based on transaction cost economics as well as the industrial marketing and purchasing (IMP) group researchers who commonly adopt the so-called context perspective, assuming relationships as distinct antecedents of performance outcomes. A framework unique to the IMP group is the activities–resources–actors (ARA) model, which posits three layers, or dimensions, characterizing relationships: activity links, resource ties, and actor bonds. This dissertation consists of the four studies that draw on the ARA framework to investigate the performance effects of activity coordination, resource configuration, trust building, and network orchestration. First, activity coordination is a main issue in the activity-link dimension. Coordination among firms’ activities is facilitated by inter-firm interaction and information sharing. Study 1 addresses how activity coordination promotes relationship performance. Second, the resource-tie layer is related to resource configuration. Study 2 empirically tests the performance effects of resource configuration across organizations. Third, actor bonds are associated with the concepts of trust and commitment between companies. Study 3 provides a case analysis of inter-firm trust development. Finally, as the ARA model is a framework for analyzing not only business relationships but also networks, Study 4 focuses on the issue of establishing and managing inter-organizational networks to investigate a case of a trap in network orchestration.Weniger anzeigen
Baseline ecological, genetic and behavioural information is still lacking and is urgently needed to set up an efficient conservation action plan for Caucasian lynx Lynx lynx dinniki in Turkey. This dissertation investigated the diet and foraging ecology of the three largest Caucasian lynx populations occupying three major lynx habitat types in Anatolia, the Asian part of Turkey. I also studied the spatial organisation and genetic variation as well as interactions between individuals of Caucasian lynx in a study area in northwestern Anatolia where I benefitted from long-term monitoring efforts started in 2009. In Chapter 2, I quantified the diet, prey preferences and functional response of three Caucasian lynx populations in Anatolia from a comparative perspective of European Eurasian lynx populations. The diet of the Eurasian lynx in Anatolia consists mostly of brown hares Lepus europaeus (78 % - 99 % of prey biomass consumed). Its foraging ecology fulfils expectations for a lagomorph specialist, similar to Iberian lynx Lynx pardinus and Canadian lynx Lynx canadensis in other ecosystems. Caucasian lynx in Anatolia display comparable body sizes and physiological requirements to individuals of other lagomorph specialist lynx species and consume half the daily food required to sustain a European Eurasian lynx individual. There was a high incidence of cannibalism, an aggressive behaviour that has very rarely observed in low density European lynx populations, observed in two ecosystems in Anatolia. In Chapter 3, I used nuclear molecular markers to investigate how sampling methodology can affect measures of genetic diversity if the population contains male territorial residents, other male residents and females are philopatric. I contrasted ‘invasive’ sampling, where tissue samples are obtained from individuals caught in box traps, with ‘non-invasive’ sampling, which requires the search and collection of faecal samples (in my case optimised through the training and use of a domestic dog trained to find lynx faeces) and the use of camera trapping. The results demonstrated that ‘invasive’ sampling was an inefficient technique and biased in favour of sampling particular territorial individuals and their offspring, thereby underestimating the true genetic variation in the population. ‘Non-invasive’ faecal sampling resulted in a less biased sampling of all sexes and classes of residents, an improved estimate of genetic diversity measures and a significantly higher level of genetic diversity obtained. The results indicate a high genetic diversity and no signs of inbreeding for northwest Anatolian lynx. Non-invasive faecal sampling not only provides more reliable genetic diversity measures but also delivers additional information on other important aspects of the biology and ecology of the same population, including diet, spatial organization and the presence of female philopatry, which in turn can help to inform conservation management planning. In Chapter 4, I investigated the spatial behaviour and population density of a northwest Anatolian Caucasian lynx population through GPS tracking of nine lynx individuals and camera trapping. The results indicated that Caucasian lynx in this study area have the smallest mean territorial female and male kernel density distribution (KUD) and minimum convex polygon (MCP) home ranges (females: 95% KUD = 46±8, 100% MCP = 49±16; males: 95% KUD = 176±3, 100% MCP = 183±5) ever reported for Eurasian lynx and a high density (4.9 lynx/100km2), on a level comparable to southern Anatolia. A different prey type, a high prey density and the absence of exploitation of this lynx population are likely drivers of the observed small home ranges. The detailed results revealed two male spatial tactics associated with separate life history stages – adult males start their residency in a population as resident floaters, ranging across huge home ranges and queuing for a territory, probably for several years. Territorial residents defend small territories. It is at present unclear whether territorial residents and / or floaters are candidate males to father the offspring of the resident philopatric females. A landscape fully occupied by adult territorial individuals is likely the cause of late territory establishment in male lynx and the large home range sizes of floaters. In this respect, Caucasian lynx resemble the spatial organisation of cheetahs Acinonyx jubatus, where the existence of floaters queuing for territories has also been documented in high density populations in eastern and southern Africa. This thesis sheds light on foraging ecology, diet, spatial organization and behaviour and genetic variability of Caucasian lynx in Anatolia. It also provides baseline information required to set up a conservation action plan of Caucasian lynx in Anatolia. For such an action plan to become effective, the non-invasive population genetics and density estimate methods applied in this study will be an essential tool for the assessment of the status of other Caucasian lynx populations in Anatolia and elsewhere.Weniger anzeigen
The current doctoral thesis focused on the development of mussel-inspired antifouling polyglycerol coatings for the prevention of biomaterial-related fouling.
In the first publication of this thesis, a coating based on the combination of mussel-inspired dendritic polyglycerol (MI-dPG) and linear polyglycerol (lPG) was successfully developed. Titanium dioxide (TiO2) was selected as a medically relevant substrate material. The formation and stability of the novel coating were confirmed by means of water contact angle measurements (CA), X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM), and atomic force microscopy (AFM). Measurements with a quartz crystal microbalance with dissipation monitoring confirmed the protein repelling properties of MI-dPG–lPG. Furthermore, cell culturing experiments showed that the MI-dPG–lPG system successfully reduced the adhesion of human umbilical vein endothelial cells. All results were compared to a similar MI-dPG coating that was post-functionalized with polyethylene glycol (PEG). The lPG-functionalized coating outperformed the PEG-functionalized coating in terms of stability and antifouling performance.
In the second publication of this thesis, the MI-dPG–lPG coating was applied as a blood contacting biomaterial for the reduction of biomaterial-induced thrombosis in ventricular assist devices (VADs). Again, TiO2 was selected as the substrate material, as it is commonly used for the production of VADs. The biocompatibility of the MI-dPG–lPG coating was shown via cell culturing experiments with human adenocarcinomic alveolar basal epithelial cells and chicken fibroblast cells. Additionally, the biocompatibility of the coating was confirmed via complement activation tests. Furthermore, the cell culturing experiments clearly indicated that the MI-dPG–lPG coating prevented cellular adhesion. Most importantly, tests with platelet rich plasma and whole blood showed that the MI-dPG–lPG coating prevented the adhesion and activation of blood platelets under static and medically relevant flow conditions. Again, the results were compared to a MI-dPG coating which was functionalized with PEG. The MI-dPG–lPG system outperformed the MI-dPG–PEG system in terms of antifouling performance and hemocompatibility. Finally, a prototype VAD (kindly provided by Berlin Heart GmbH) was coated with MI-dPG under industrially relevant flow conditions. The successful functionalization of the VAD system with MI-dPG was shown via fluorescence experiments.
In the last publication of this thesis, the MI-dPG coating was utilized as a platform for the direct grafting of dPG from the surface, for the introduction of antifouling surface properties to medically relevant TiO2 and polydimethylsiloxane (PDMS). The successful grafting of dPG from MI-dPG was confirmed by means of CA, XPS, and SEM measurements. The results showed that in the absence of the MI-dPG coating, the dPG grafting process only occurred insufficiently from the TiO2 substrate (i.e., through the hydroxyl moieties present on the surface of TiO2). In case of the PDMS substrate, dPG grafting did not occur in the absence of MI-dPG. Cell culturing experiments showed that upon the grafting of dPG from MI-dPG highly biocompatible but cytophobic surfaces were obtained (> 95% reduction in cell adhesion for both cell types).Weniger anzeigen
Polyhalogen chemistry receives great attention due to its structural diversity and increasing possible applications. This diversity can be expanded by using interhalogens, such as BrCl, exploiting its more pronounced σ-hole compared to the halogens Cl2 and Br2. However, because of its equilibrium with Cl2 and Br2, the stoichiometric usage of neat BrCl as a reagent is hampered. Consequently, an improved in situ synthesis route for BrCl based interhalogen compounds is introduced. The presented addition of a halogen bond acceptor (e.g. Cl–) results in an almost entire shift of the equilibrium to the BrCl side (>99.99 %). This enables the stabilization and crystallographic characterization of a complete set of non-classical polyinterhalogen monoanions [Cl(BrCl)n]– (n = 2 – 6), which consist of a central chloride that is coordinated by two to six BrCl molecules, respectively. The reported octahedral structural motif of the [Cl(BrCl)6]– monoanion in [PNP][Cl(BrCl6)] is very rare in polyhalogen chemistry and represents the first tridecahalogen anion. Additionally, easy-to-handle room temperature ionic liquids based on BrCl have been investigated in interhalogenation reactions of alkenes, alkynes and Michael systems. As a further development, it was possible to expand the concept of halogen bonding to the pseudohalogen cyanogen bromide (BrCN). Accordingly, the non-symmetric pseudohalogen BrCN can be compared to interhalogens such as IBr and BrCl. Herein, a new class of polypseudohalogen compounds based on BrCN, including the almost linear [Br(BrCN)]– as well as the distorted trigonal-pyramidal [Br(BrCN)3]–, is presented. Both structures were characterized by XRD, Raman spectroscopy and quantum-chemical calculations. Moreover, the dynamic behavior of these compounds in solution and as room temperature ionic liquid was studied by 13C and 15N NMR spectroscopy. The significantly reduced vapor pressure of these reactive ionic liquids compared to neat BrCN, combined with the ability to dissolve elemental gold are promising applications for ongoing research.Weniger anzeigen
The Insulinoma-associated 1 (Insm1) zinc finger transcription factor is highly expressed in the embryonic nervous system and its expression is maintained in the neurogenic areas of the adult brain. Insm1 is a direct target of Ascl1 and has been shown to be important for neuronal differentiation (Wildner et al., 2008; Farkas et al., 2008; Masserdotti et al., 2015; Monaghan et al., 2017). However, the understanding of Insm1 molecular network has remained limited. Here, I sought to undertake a genomic approach to decipher Insm1-dependent molecular mechanisms controlling the progression of neuronal progenitor cells. To this end, I generated datasets of Insm1-dependent expression profiling and its genomic binding profile. Interestingly, Insm1 occupies genomic regions located nearby genes of the Notch signaling pathway. In vivo and in vitro studies showed that mutation of Insm1 in neuronal progenitor cells results in upregulation of Notch signaling components, such as Notch1, Dll1 and Hes1. In vitro analyses illustrate that Insm1 directly represses the expression of these genes. I propose that Insm1 represses the progenitor program downstream of Ascl1 in neurogenesis. Importantly, I show that Insm1 exerts its functions by directly controlling the expression of neuronal target genes and repressing non-neuronal genes. Altogether, this genomic analysis reveals the complex molecular program regulated by Insm1 for the correct establishment of neuronal differentiation through both genetic and epigenetic mechanisms.Weniger anzeigen