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Synapses are the fundamental structures that regulate the functionality of the neural circuit. The ability of the synapse to modulate its structure and function at a fast rate due to various sensory inputs provides the strength to the nervous system to incorporate new adaptations and behaviors in the animal. The synapses are very dynamic throughout the life of the animal starting from early development. Continuous events of formation and elimination of synapse, activation and inhibition of synaptic function are observed in almost all synapses. These processes occur at a high speed and require controlled cellular mechanisms. Imbalance in these processes results in defective nervous system and has been reported in many neurological disorders. Thus, it is important to understand the mechanisms that regulate process of synapse development maintenance and function.
Kinases and phosphatases are the key regulators of cellular mechanisms. Understanding the function of these molecules in the neuron will shed light on the molecular mechanisms of synaptic plasticity. Using Drosophila melanogaster larval neuromuscular junction as a model, Bulat et al. (2014) performed a large RNAi based screen targeting kinome and phosphatome of Drosophila to identify the essential kinases and phosphatases and found Myeloid leukemia factor-1 adaptor molecule (Madm) and Protein phosphatase 4 (PP4) as novel regulators of synapse development and maintenance. The function of these molecules in the nervous system has not been reported and hence I investigated on the role of Madm and PP4 in the regulation of synapse development, maintenance and function.
Myeloid leukemia factor-1 adaptor molecule (Madm), a ubiquitously expressing psuedokinase essentially functions to regulate synaptic growth, stability and function. Using a combination of genetic and high throughput imaging, I could demonstrate that Madm functions to regulate the synaptic growth and stability from the presynapse and synaptic organization form the postsynapse. Also, I could demonstrate that Madm functions in association with mTOR pathway to regulate synapse growth acting downstream of 4E-BP. In addition, using electrophysiology, we could demonstrate that Madm is essential for the basic synaptic transmission with an additive function of retrograde synaptic potentiation. In summary, I could demonstrate that Madm is a novel regulator of synaptic development, maintenance and function.
Protein phosphatase 4 (PP4), a ubiquitously expressing protein phosphatase is involved in the regulation of multiple aspects of the nervous system. I could demonstrate that PP4 is essential for the development of nervous system and the metamorphosis. Using genetics and imaging analysis, I could demonstrate that loss of PP4 results in the abnormal morphology of cell organelles. In addition, I could show that loss of PP4 results in defective brain development with poorly developed structures.
Altogether, in this study, I could demonstrate the importance of novel molecules, a pesudokinase Madm and protein phosphatases PP4 in the nervous system to regulate distinct aspects of the neuron.
Hardware Contention-Aware Real-Time Scheduling on Multi-Core Platforms in Safety-Critical Systems
(2019)
While the computing industry has shifted from single-core to multi-core processors for performance gain, safety-critical systems (SCSs) still require solutions that enable their transition while guaranteeing safety, requiring no source-code modifications and substantially reducing re-development and re-certification costs, especially for legacy applications that are typically substantial. This dissertation considers the problem of worst-case execution time (WCET) analysis under contentions when deadline-constrained tasks in independent partitioned task set execute on a homogeneous multi-core processor with dynamic time-triggered shared memory bandwidth partitioning in SCSs.
Memory bandwidth in multi-core processors is shared across cores and is a significant cause of performance bottleneck and temporal variability of multiple-orders in task’s execution times due to contentions in memory sub-system. Further, the circular dependency is not only between WCET and CPU scheduling of others cores, but also between WCET and memory bandwidth assignments over time to cores. Thus, there is need of solutions that allow tailoring memory bandwidth assignments to workloads over time and computing safe WCET. It is pragmatically infeasible to obtain WCET estimates from static WCET analysis tools for multi-core processors due to the sheer computational complexity involved.
We use synchronized periodic memory servers on all cores that regulate each core’s maximum memory bandwidth based on allocated bandwidth over time. First, we present a workload schedulability test for known even-memory-bandwidth-assignment-to-active-cores over time, where the number of active cores represents the cores with non-zero memory bandwidth assignment. Its computational complexity is similar to merge-sort. Second, we demonstrate using a real avionics certified safety-critical application how our method’s use can preserve an existing application’s single-core CPU schedule under contentions on a multi-core processor. It enables incremental certification using composability and requires no-source code modification.
Next, we provide a general framework to perform WCET analysis under dynamic memory bandwidth partitioning when changes in memory bandwidth to cores assignment are time-triggered and known. It provides a stall maximization algorithm that has a complexity similar to a concave optimization problem and efficiently implements the WCET analysis. Last, we demonstrate dynamic memory assignments and WCET analysis using our method significantly improves schedulability compared to the stateof-the-art using an Integrated Modular Avionics scenario.
Visualization is vital to the scientific discovery process.
An interactive high-fidelity rendering provides accelerated insight into complex structures, models and relationships.
However, the efficient mapping of visualization tasks to high performance architectures is often difficult, being subject to a challenging mixture of hardware and software architectural complexities in combination with domain-specific hurdles.
These difficulties are often exacerbated on heterogeneous architectures.
In this thesis, a variety of ray casting-based techniques are developed and investigated with respect to a more efficient usage of heterogeneous HPC systems for distributed visualization, addressing challenges in mesh-free rendering, in-situ compression, task-based workload formulation, and remote visualization at large scale.
A novel direct raytracing scheme for on-the-fly free surface reconstruction of particle-based simulations using an extended anisoptropic kernel model is investigated on different state-of-the-art cluster setups.
The versatile system renders up to 170 million particles on 32 distributed compute nodes at close to interactive frame rates at 4K resolution with ambient occlusion.
To address the widening gap between high computational throughput and prohibitively slow I/O subsystems, in situ topological contour tree analysis is combined with a compact image-based data representation to provide an effective and easy-to-control trade-off between storage overhead and visualization fidelity.
Experiments show significant reductions in storage requirements, while preserving flexibility for exploration and analysis.
Driven by an increasingly heterogeneous system landscape, a flexible distributed direct volume rendering and hybrid compositing framework is presented.
Based on a task-based dynamic runtime environment, it enables adaptable performance-oriented deployment on various platform configurations.
Comprehensive benchmarks with respect to task granularity and scaling are conducted to verify the characteristics and potential of the novel task-based system design.
A core challenge of HPC visualization is the physical separation of visualization resources and end-users.
Using more tiles than previously thought reasonable, a distributed, low-latency multi-tile streaming system is demonstrated, being able to sustain a stable 80 Hz when streaming up to 256 synchronized 3840x2160 tiles and achieve 365 Hz at 3840x2160 for sort-first compositing over the internet, thereby enabling lightweight visualization clients and leaving all the heavy lifting to the remote supercomputer.
Many loads acting on a vehicle depend on the condition and quality of roads
traveled as well as on the driving style of the motorist. Thus, during vehicle development,
good knowledge on these further operations conditions is advantageous.
For that purpose, usage models for different kinds of vehicles are considered. Based
on these mathematical descriptions, representative routes for multiple user
types can be simulated in a predefined geographical region. The obtained individual
driving schedules consist of coordinates of starting and target points and can
thus be routed on the true road network. Additionally, different factors, like the
topography, can be evaluated along the track.
Available statistics resulting from travel survey are integrated to guarantee reasonable
trip length. Population figures are used to estimate the number of vehicles in
contained administrative units. The creation of thousands of those geo-referenced
trips then allows the determination of realistic measures of the durability loads.
Private as well as commercial use of vehicles is modeled. For the former, commuters
are modeled as the main user group conducting daily drives to work and
additional leisure time a shopping trip during workweek. For the latter, taxis as
example for users of passenger cars are considered. The model of light-duty commercial
vehicles is split into two types of driving patterns, stars and tours, and in
the common traffic classes of long-distance, local and city traffic.
Algorithms to simulate reasonable target points based on geographical and statistical
data are presented in detail. Examples for the evaluation of routes based
on topographical factors and speed profiles comparing the influence of the driving
style are included.
Shared memory concurrency is the pervasive programming model for multicore architectures
such as x86, Power, and ARM. Depending on the memory organization, each architecture follows
a somewhat different shared memory model. All these models, however, have one common
feature: they allow certain outcomes for concurrent programs that cannot be explained
by interleaving execution. In addition to the complexity due to architectures, compilers like
GCC and LLVM perform various program transformations, which also affect the outcomes of
concurrent programs.
To be able to program these systems correctly and effectively, it is important to define a
formal language-level concurrency model. For efficiency, it is important that the model is
weak enough to allow various compiler optimizations on shared memory accesses as well
as efficient mappings to the architectures. For programmability, the model should be strong
enough to disallow bogus “out-of-thin-air” executions and provide strong guarantees for well-synchronized
programs. Because of these conflicting requirements, defining such a formal
model is very difficult. This is why, despite years of research, major programming languages
such as C/C++ and Java do not yet have completely adequate formal models defining their
concurrency semantics.
In this thesis, we address this challenge and develop a formal concurrency model that is very
good both in terms of compilation efficiency and of programmability. Unlike most previous
approaches, which were defined either operationally or axiomatically on single executions,
our formal model is based on event structures, which represents multiple program executions,
and thus gives us more structure to define the semantics of concurrency.
In more detail, our formalization has two variants: the weaker version, WEAKEST, and the
stronger version, WEAKESTMO. The WEAKEST model simulates the promising semantics proposed
by Kang et al., while WEAKESTMO is incomparable to the promising semantics. Moreover,
WEAKESTMO discards certain questionable behaviors allowed by the promising semantics.
We show that the proposed WEAKESTMO model resolve out-of-thin-air problem, provide
standard data-race-freedom (DRF) guarantees, allow the desirable optimizations, and can be
mapped to the architectures like x86, PowerPC, and ARMv7. Additionally, our models are
flexible enough to leverage existing results from the literature to establish data-race-freedom
(DRF) guarantees and correctness of compilation.
In addition, in order to ensure the correctness of compilation by a major compiler, we developed
a translation validator targeting LLVM’s “opt” transformations of concurrent C/C++
programs. Using the validator, we identified a few subtle compilation bugs, which were reported
and were fixed. Additionally, we observe that LLVM concurrency semantics differs
from that of C11; there are transformations which are justified in C11 but not in LLVM and
vice versa. Considering the subtle aspects of LLVM concurrency, we formalized a fragment
of LLVM’s concurrency semantics and integrated it into our WEAKESTMO model.
In this thesis, we deal with the worst-case portfolio optimization problem occuring in discrete-time markets.
First, we consider the discrete-time market model in the presence of crash threats. We construct the discrete worst-case optimal portfolio strategy by the indifference principle in the case of the logarithmic utility. After that we extend this problem to general utility functions and derive the discrete worst-case optimal portfolio processes, which are characterized by a dynamic programming equation. Furthermore, the convergence of the discrete worst-case optimal portfolio processes are investigated when we deal with the explicit utility functions.
In order to further study the relation of the worst-case optimal value function in discrete-time models to continuous-time models we establish the finite-difference approach. By deriving the discrete HJB equation we verify the worst-case optimal value function in discrete-time models, which satisfies a system of dynamic programming inequalities. With increasing degree of fineness of the time discretization, the convergence of the worst-case value function in discrete-time models to that in continuous-time models are proved by using a viscosity solution method.
Carotenoids are organic lipophilic tetraterpenes ubiquitously present in Nature and found across the three domains of life (Archaea, Bacteria and Eukaryotes). Their structure is characterized by an extensive conjugated double-bond system, which serves as a light-absorbing chromophore, hence determining its colour, and enables carotenoids to absorb energy from other molecules and to act as antioxidant agents. Humans obtain carotenoids mainly via the consumption of fruits and vegetables, and to a smaller extent from other food sources such as fish and eggs. The concentration of carotenoids in the human plasma and tissues has been positively associated with a lower incidence of several chronic diseases including, cancer, diabetes, macular degeneration and cardiovascular conditions, likely due to their antioxidant properties. However, an important aspect of carotenoids, namely β- and α-carotene and β-cryptoxanthin, in human health and development, is their potential to be converted by the body into Vitamin A.
Yet, bioavailability of carotenoids is relatively low (< 30%) and dependent, among others, on dietary factors, such as amount and type of dietary lipids and the presence of dietary fibres. One dietary factor that has been found to negatively impact carotenoid bioaccessibility and cellular uptake in vitro is high concentrations of divalent cations during simulated gastro-intestinal digestion. Nevertheless, the mechanism of action of divalent cations remains unclear. The goal of this thesis was to better understand how divalent cations act during digestion and modulate carotenoid bioavailability. In vitro trials of simulated gastro-intestinal digestion and cellular uptake were run to investigate how varying concentrations of calcium, magnesium and zinc affected the bioaccessibility of both pure carotenoids and carotenoids from food matrices. In order to validate or refute results obtained in vitro, a randomized and double blinded placebo controlled cross-over postprandial trial (24 male participants) was carried out, testing the effect of 3 supplementary calcium doses (0 mg, 500 mg and 1000 mg) on the bioavailability of carotenoids from a spinach based meal. In vitro trials showed that addition of the divalent cations significantly decreased the bioaccessibility of both pure carotenoids (P < 0.001) and those from food matrices (P < 0.01). This effect was dependent on the type of mineral and its concentration. Strongest effects were seen for increasing concentrations of calcium followed by magnesium and zinc. The addition of divalent cations also altered the physico-chemical properties, i.e. viscosity and surface tension, of the digestas. However, the extent of this effect varied according to the type of matrix. The effects on bioaccessibility and physico-chemical properties were accompanied by variations of the zeta-potential of the particles in solution. Taken together, results from the in vitro trials strongly suggested that divalent cations were able to bind bile salts and other surfactant agents, affecting their solubility. The observed i) decrease in macroviscosity, ii) increase in surface tension, and the iii) reduction of the zeta-potential of the digesta, confirmed the removal of surfactant agents from the system, most likely due to precipitation as a result of the lower solubility of the mineral-surfactant complexes. As such, micellarization of carotenoids was hindered, explaining their reduced bioaccessibility. As for the human trial, results showed that there was no significant influence of supplementation with either 500 or 1000 mg of supplemental calcium (in form of carbonate) on the bioavailability of a spinach based meal, as measured by the area-under curve of carotenoid concentrations in the plasma-triacylglycerol rich fraction, suggesting that the in vitro results are not supported in such an in vivo scenario, which may be explained by the initial low bioaccessibility of spinach carotenoids and the dissolution kinetics of the calcium pills. Further investigations are necessary to understand how divalent cations act during in vivo digestion and potentially interact with lipophilic nutrients and food constituents.
The systems in industrial automation management (IAM) are information systems. The management parts of such systems are software components that support the manufacturing processes. The operational parts control highly plug-compatible devices, such as controllers, sensors and motors. Process variability and topology variability are the two main characteristics of software families in this domain. Furthermore, three roles of stakeholders -- requirement engineers, hardware-oriented engineers, and software developers -- participate in different derivation stages and have different variability concerns. In current practice, the development and reuse of such systems is costly and time-consuming, due to the complexity of topology and process variability. To overcome these challenges, the goal of this thesis is to develop an approach to improve the software product derivation process for systems in industrial automation management, where different variability types are concerned in different derivation stages. Current state-of-the-art approaches commonly use general-purpose variability modeling languages to represent variability, which is not sufficient for IAM systems. The process and topology variability requires more user-centered modeling and representation. The insufficiency of variability modeling leads to low efficiency during the staged derivation process involving different stakeholders. Up to now, product line approaches for systematic variability modeling and realization have not been well established for such complex domains. The model-based derivation approach presented in this thesis integrates feature modeling with domain-specific models for expressing processes and topology. The multi-variability modeling framework includes the meta-models of the three variability types and their associations. The realization and implementation of the multi-variability involves the mapping and the tracing of variants to their corresponding software product line assets. Based on the foundation of multi-variability modeling and realization, a derivation infrastructure is developed, which enables a semi-automated software derivation approach. It supports the configuration of different variability types to be integrated into the staged derivation process of the involved stakeholders. The derivation approach is evaluated in an industry-grade case study of a complex software system. The feasibility is demonstrated by applying the approach in the case study. By using the approach, both the size of the reusable core assets and the automation level of derivation are significantly improved. Furthermore, semi-structured interviews with engineers in practice have evaluated the usefulness and ease-of-use of the proposed approach. The results show a positive attitude towards applying the approach in practice, and high potential to generalize it to other related domains.
Function of two redox sensing kinases from the methanogenic archaeon Methanosarcina acetivorans
(2019)
MsmS is a heme-based redox sensor kinase in Methanosarcina acetivorans consisting of alternating PAS and GAF domains connected to a C-terminal kinase domain. In addition to MsmS, M. acetivorans possesses a second kinase, MA0863 with high sequence similarity. Interestingly, MA0863 possesses an amber codon in its second GAF domain, encoding for the amino acid pyrrolysine. Thus far, no function of this residue has been resolved. In order to examine the heme iron coordination in both proteins, an improved method for the production of heme proteins was established using the Escherichia coli strain Nissle 1917. This method enables the complete reconstitution of a recombinant hemoprotein during protein production, thereby resulting in a native heme coordination. Analysis of the full-length MsmS and MA0863 confirmed a covalently bound heme cofactor, which is connected to one conserved cysteine residue in each protein. In order to identify the coordinating amino acid residues of the heme iron, UV/vis spectra of different variants were measured. These studies revealed His702 in MsmS and the corresponding His666 in MA0863 as the proximal heme ligands. MsmS has previously been described as a heme-based redox sensor. In order to examine whether the same is true for MA0863, redox dependent kinase assays were performed. MA0863 indeed displays redox dependent autophosphorylation activity, which is independent of heme ligands and only observed under oxidizing conditions. Interestingly, autophosphorylation was shown to be independent of the heme cofactor but rather relies on thiol oxidation. Therefore, MA0863 was renamed in RdmS (redox dependent methyltransferase-associated sensor). In order to identify the phosphorylation site of RdmS, thin layer chromatography was performed identifying a tyrosine as the putative phosphorylation site. This observation is in agreement with the lack of a so-called H-box in typical histidine kinases. Due to their genomic localization, MsmS and RdmS were postulated to form two-component systems (TCS) with vicinal encoded regulator proteins MsrG and MsrF. Therefore, protein-protein interaction studies using the bacterial adenylate two hybrid system were performed suggesting an interaction of RdmS and MsmS with the three regulators MsrG/F/C. Due to these multiple interactions these signal transduction pathways should rather be considered multicomponent system instead of two component systems.
Destructive diseases of the lung like lung cancer or fibrosis are still often lethal. Also in case of fibrosis in the liver, the only possible cure is transplantation.
In this thesis, we investigate 3D micro computed synchrotron radiation (SR\( \mu \)CT) images of capillary blood vessels in mouse lungs and livers. The specimen show so-called compensatory lung growth as well as different states of pulmonary and hepatic fibrosis.
During compensatory lung growth, after resecting part of the lung, the remaining part compensates for this loss by extending into the empty space. This process is accompanied by an active vessel growing.
In general, the human lung can not compensate for such a loss. Thus, understanding this process in mice is important to improve treatment options in case of diseases like lung cancer.
In case of fibrosis, the formation of scars within the organ's tissue forces the capillary vessels to grow to ensure blood supply.
Thus, the process of fibrosis as well as compensatory lung growth can be accessed by considering the capillary architecture.
As preparation of 2D microscopic images is faster, easier, and cheaper compared to SR\( \mu \)CT images, they currently form the basis of medical investigation. Yet, characteristics like direction and shape of objects can only properly be analyzed using 3D imaging techniques. Hence, analyzing SR\( \mu \)CT data provides valuable additional information.
For the fibrotic specimen, we apply image analysis methods well-known from material science. We measure the vessel diameter using the granulometry distribution function and describe the inter-vessel distance by the spherical contact distribution. Moreover, we estimate the directional distribution of the capillary structure. All features turn out to be useful to characterize fibrosis based on the deformation of capillary vessels.
It is already known that the most efficient mechanism of vessel growing forms small torus-shaped holes within the capillary structure, so-called intussusceptive pillars. Analyzing their location and number strongly contributes to the characterization of vessel growing. Hence, for all three applications, this is of great interest. This thesis provides the first algorithm to detect intussusceptive pillars in SR\( \mu \)CT images. After segmentation of raw image data, our algorithm works automatically and allows for a quantitative evaluation of a large amount of data.
The analysis of SR\( \mu \)CT data using our pillar algorithm as well as the granulometry, spherical contact distribution, and directional analysis extends the current state-of-the-art in medical studies. Although it is not possible to replace certain 3D features by 2D features without losing information, our results could be used to examine 2D features approximating the 3D findings reasonably well.
In computer graphics, realistic rendering of virtual scenes is a computationally complex problem. State-of-the-art rendering technology must become more scalable to
meet the performance requirements for demanding real-time applications.
This dissertation is concerned with core algorithms for rendering, focusing on the
ray tracing method in particular, to support and saturate recent massively parallel computer systems, i.e., to distribute the complex computations very efficiently
among a large number of processing elements. More specifically, the three targeted
main contributions are:
1. Collaboration framework for large-scale distributed memory computers
The purpose of the collaboration framework is to enable scalable rendering
in real-time on a distributed memory computer. As an infrastructure layer it
manages the explicit communication within a network of distributed memory
nodes transparently for the rendering application. The research is focused on
designing a communication protocol resilient against delays and negligible in
overhead, relying exclusively on one-sided and asynchronous data transfers.
The hypothesis is that a loosely coupled system like this is able to scale linearly
with the number of nodes, which is tested by directly measuring all possible
communication-induced delays as well as the overall rendering throughput.
2. Ray tracing algorithms designed for vector processing
Vector processors are to be efficiently utilized for improved ray tracing performance. This requires the basic, scalar traversal algorithm to be reformulated
in order to expose a high degree of fine-grained data parallelism. Two approaches are investigated: traversing multiple rays simultaneously, and performing
multiple traversal steps at once. Efficiently establishing coherence in a group
of rays as well as avoiding sorting of the nodes in a multi-traversal step are the
defining research goals.
3. Multi-threaded schedule and memory management for the ray tracing acceleration structure
Construction times of high-quality acceleration structures are to be reduced by
improvements to multi-threaded scalability and utilization of vector processors. Research is directed at eliminating the following scalability bottlenecks:
dynamic memory growth caused by the primitive splits required for high-
quality structures, and top-level hierarchy construction where simple task par-
allelism is not readily available. Additional research addresses how to expose
scatter/gather-free data-parallelism for efficient vector processing.
Together, these contributions form a scalable, high-performance basis for real-time,
ray tracing-based rendering, and a prototype path tracing application implemented
on top of this basis serves as a demonstration.
The key insight driving this dissertation is that the computational power necessary
for realistic light transport for real-time rendering applications demands massively
parallel computers, which in turn require highly scalable algorithms. Therefore this
dissertation provides important research along the path towards virtual reality.
Novel image processing techniques have been in development for decades, but most
of these techniques are barely used in real world applications. This results in a gap
between image processing research and real-world applications; this thesis aims to
close this gap. In an initial study, the quantification, propagation, and communication
of uncertainty were determined to be key features in gaining acceptance for
new image processing techniques in applications.
This thesis presents a holistic approach based on a novel image processing pipeline,
capable of quantifying, propagating, and communicating image uncertainty. This
work provides an improved image data transformation paradigm, extending image
data using a flexible, high-dimensional uncertainty model. Based on this, a completely
redesigned image processing pipeline is presented. In this pipeline, each
step respects and preserves the underlying image uncertainty, allowing image uncertainty
quantification, image pre-processing, image segmentation, and geometry
extraction. This is communicated by utilizing meaningful visualization methodologies
throughout each computational step.
The presented methods are examined qualitatively by comparing to the Stateof-
the-Art, in addition to user evaluation in different domains. To show the applicability
of the presented approach to real world scenarios, this thesis demonstrates
domain-specific problems and the successful implementation of the presented techniques
in these domains.
Glycine constitutes the major neurotransmitter at inhibitory synapses of lower brain regions.
A rapid removal of glycine from the synaptic cleft and consequent recycling is crucial for
synaptic transmission in systems with high effort on temporal precision. This is mainly
achieved by glycine translocation via two glycine transporters (GlyTs), namely GlyT1 and
GlyT2. At inhibitory synapses, GlyT2 was found to be specifically expressed by neurons,
supplying the presynapse with glycine needed for vesicle filling. In contrast, GlyT1 is attributed
to astrocytes and primarily mediates the termination of synaptic transmission by glycine
removal from the synaptic cleft. Employing patch-clamp recordings from principal neurons of
the lateral superior olive (LSO) in acute brainstem slices of GlyT1b/c knockout (KO) mice and
wildtype (WT) littermates at postnatal day 20, I analyzed how postsynaptic responses are
changed in a GlyT1-depleted environment. During spontaneous vesicle release I found no
change of postsynaptic responses, contradicting my initial hypothesis of prolonged decay
times. Electrical stimulation of fibers of the medial nucleus of the trapezoid body (MNTB),
which are known to form fast, reliable and highly precise synapses with LSO principal neurons,
revealed that GlyT1 is involved in proper synaptic function during sustained, high frequent
synaptic transmission. Stimulation with 50 Hz led to a stronger decay time and latency
prolongation in GlyT1b/c KO, accelerating to 60% longer decay times and 30% longer latencies.
Additionally, a more pronounced frequency-dependent depression and fidelity decrease was
observed during stimulation with 200 Hz in GlyT1b/c KO, resulting in 67% smaller amplitudes
and only 25% of WT fidelity at the end of the challenge. Basic properties like readily releasable
pool, release probability, and quantal size (q) were not altered in GlyT1b/c KO, but
interestingly q decreased during 50 Hz and 100 Hz challenges to about 84%, which was not
observed in WT. I conclude that stronger accumulation of extracellular glycine due to GlyT1
loss leads to prolonged activation of postsynaptic glycine receptors (GlyRs). As a further
consequence, activation of presynaptic GlyRs in the vicinity of the synaptic cleft might be
enhanced, accompanied by a stronger occurrence of shunting inhibition. Furthermore, I
assume a GlyT1-dependent glycine shuttle, which is absent at GlyT1b/c KO synapses. This
could result in a diminished glycine supply to GlyT2 located at more distant sites, causing a
disturbed replenishment during periods with excess release of glycine. Conclusively, my study
reveals a contribution of astrocytes in fast and reliable synaptic transmission at the MNTB-LSO
synapse, which in turn is crucial for proper sound source localization.
Magnetoelastic coupling describes the mutual dependence of the elastic and magnetic fields and can be observed in certain types of materials, among which are the so-called "magnetostrictive materials". They belong to the large class of "smart materials", which change their shape, dimensions or material properties under the influence of an external field. The mechanical strain or deformation a material experiences due to an externally applied magnetic field is referred to as magnetostriction; the reciprocal effect, i.e. the change of the magnetization of a body subjected to mechanical stress is called inverse magnetostriction. The coupling of mechanical and electromagnetic fields is particularly observed in "giant magnetostrictive materials", alloys of ferromagnetic materials that can exhibit several thousand times greater magnitudes of magnetostriction (measured as the ratio of the change in length of the material to its original length) than the common magnetostrictive materials. These materials have wide applications areas: They are used as variable-stiffness devices, as sensors and actuators in mechanical systems or as artificial muscles. Possible application fields also include robotics, vibration control, hydraulics and sonar systems.
Although the computational treatment of coupled problems has seen great advances over the last decade, the underlying problem structure is often not fully understood nor taken into account when using black box simulation codes. A thorough analysis of the properties of coupled systems is thus an important task.
The thesis focuses on the mathematical modeling and analysis of the coupling effects in magnetostrictive materials. Under the assumption of linear and reversible material behavior with no magnetic hysteresis effects, a coupled magnetoelastic problem is set up using two different approaches: the magnetic scalar potential and vector potential formulations. On the basis of a minimum energy principle, a system of partial differential equations is derived and analyzed for both approaches. While the scalar potential model involves only stationary elastic and magnetic fields, the model using the magnetic vector potential accounts for different settings such as the eddy current approximation or the full Maxwell system in the frequency domain.
The distinctive feature of this work is the analysis of the obtained coupled magnetoelastic problems with regard to their structure, strong and weak formulations, the corresponding function spaces and the existence and uniqueness of the solutions. We show that the model based on the magnetic scalar potential constitutes a coupled saddle point problem with a penalty term. The main focus in proving the unique solvability of this problem lies on the verification of an inf-sup condition in the continuous and discrete cases. Furthermore, we discuss the impact of the reformulation of the coupled constitutive equations on the structure of the coupled problem and show that in contrast to the scalar potential approach, the vector potential formulation yields a symmetric system of PDEs. The dependence of the problem structure on the chosen formulation of the constitutive equations arises from the distinction of the energy and coenergy terms in the Lagrangian of the system. While certain combinations of the elastic and magnetic variables lead to a coupled magnetoelastic energy function yielding a symmetric problem, the use of their dual variables results in a coupled coenergy function for which a mixed problem is obtained.
The presented models are supplemented with numerical simulations carried out with MATLAB for different examples including a 1D Euler-Bernoulli beam under magnetic influence and a 2D magnetostrictive plate in the state of plane stress. The simulations are based on material data of Terfenol-D, a giant magnetostrictive materials used in many industrial applications.
In this dissertation we apply financial mathematical modelling to electricity markets. Electricity is different from any other underlying of financial contracts: it is not storable. This means that electrical energy in one time point cannot be transferred to another. As a consequence, power contracts with disjoint delivery time spans basically have a different underlying. The main idea throughout this thesis is exactly this two-dimensionality of time: every electricity contract is not only characterized by its trading time but also by its delivery time.
The basis of this dissertation are four scientific papers corresponding to the Chapters 3 to 6, two of which have already been published in peer-reviewed journals. Throughout this thesis two model classes play a significant role: factor models and structural models. All ideas are applied to or supported by these two model classes. All empirical studies in this dissertation are conducted on electricity price data from the German market and Chapter 4 in particular studies an intraday derivative unique to the German market. Therefore, electricity market design is introduced by the example of Germany in Chapter 1. Subsequently, Chapter 2 introduces the general mathematical theory necessary for modelling electricity prices, such as Lévy processes and the Esscher transform. This chapter is the mathematical basis of the Chapters 3 to 6.
Chapter 3 studies factor models applied to the German day-ahead spot prices. We introduce a qualitative measure for seasonality functions based on three requirements. Furthermore, we introduce a relation of factor models to ARMA processes, which induces a new method to estimate the mean reversion speed.
Chapter 4 conducts a theoretical and empirical study of a pricing method for a new electricity derivative: the German intraday cap and floor futures. We introduce the general theory of derivative pricing and propose a method based on the Hull-White model of interest rate modelling, which is a one-factor model. We include week futures prices to generate a price forward curve (PFC), which is then used instead of a fixed deterministic seasonality function. The idea that we can combine all market prices, and in particular futures prices, to improve the model quality also plays the major role in Chapter 5 and Chapter 6.
In Chapter 5 we develop a Heath-Jarrow-Morton (HJM) framework that models intraday, day-ahead, and futures prices. This approach is based on two stochastic processes motivated by economic interpretations and separates the stochastic dynamics in trading and delivery time. Furthermore, this framework allows for the use of classical day-ahead spot price models such as the ones of Schwartz and Smith (2000), Lucia and Schwartz (2002) and includes many model classes such as structural models and factor models.
Chapter 6 unifies the classical theory of storage and the concept of a risk premium through the introduction of an unobservable intrinsic electricity price. Since all tradable electricity contracts are derivatives of this actual intrinsic price, their prices should all be derived as conditional expectation under the risk-neutral measure. Through the intrinsic electricity price we develop a framework, which also includes many existing modelling approaches, such as the HJM framework of Chapter 5.
This thesis addresses several challenges for sustainable logistics operations and investigates (1) the integration of intermediate stops in the route planning of transportation vehicles, which especially becomes relevant when alternative-fuel vehicles with limited driving range or a sparse refueling infrastructure are considered, (2) the combined planning of the battery replacement infrastructure and of the routing for battery electric vehicles, (3) the use of mobile load replenishment or refueling possibilities in environments where the respective infrastructure is not available, and (4) the additional consideration of the flow of goods from the end user in backward direction to the point of origin for the purpose of, e.g., recapturing value or proper disposal. We utilize models and solution methods from the domain of operations research to gain insights into the investigated problems and thus to support managerial decisions with respect to these issues.
The focus of this work is to provide and evaluate a novel method for multifield topology-based analysis and visualization. Through this concept, called Pareto sets, one is capable to identify critical regions in a multifield with arbitrary many individual fields. It uses ideas found in graph optimization to find common behavior and areas of divergence between multiple optimization objectives. The connections between the latter areas can be reduced into a graph structure allowing for an abstract visualization of the multifield to support data exploration and understanding.
The research question that is answered in this dissertation is about the general capability and expandability of the Pareto set concept in context of visualization and application. Furthermore, the study of its relations, drawbacks and advantages towards other topological-based approaches. This questions is answered in several steps, including consideration and comparison with related work, a thorough introduction of the Pareto set itself as well as a framework for efficient implementation and an attached discussion regarding limitations of the concept and their implications for run time, suitable data, and possible improvements.
Furthermore, this work considers possible simplification approaches like integrated single-field simplification methods but also using common structures identified through the Pareto set concept to smooth all individual fields at once. These considerations are especially important for real-world scenarios to visualize highly complex data by removing small local structures without destroying information about larger, global trends.
To further emphasize possible improvements and expandability of the Pareto set concept, the thesis studies a variety of different real world applications. For each scenario, this work shows how the definition and visualization of the Pareto set is used and improved for data exploration and analysis based on the scenarios.
In summary, this dissertation provides a complete and sound summary of the Pareto set concept as ground work for future application of multifield data analysis. The possible scenarios include those presented in the application section, but are found in a wide range of research and industrial areas relying on uncertainty analysis, time-varying data, and ensembles of data sets in general.
The simulation of physical phenomena involving the dynamic behavior of fluids and gases
has numerous applications in various fields of science and engineering. Of particular interest
is the material transport behavior, the tendency of a flow field to displace parts of the
medium. Therefore, many visualization techniques rely on particle trajectories.
Lagrangian Flow Field Representation. In typical Eulerian settings, trajectories are
computed from the simulation output using numerical integration schemes. Accuracy concerns
arise because, due to limitations of storage space and bandwidth, often only a fraction
of the computed simulation time steps are available. Prior work has shown empirically that
a Lagrangian, trajectory-based representation can improve accuracy [Agr+14]. Determining
the parameters of such a representation in advance is difficult; a relationship between the
temporal and spatial resolution and the accuracy of resulting trajectories needs to be established.
We provide an error measure for upper bounds of the error of individual trajectories.
We show how areas at risk for high errors can be identified, thereby making it possible to
prioritize areas in time and space to allocate scarce storage resources.
Comparative Visual Analysis of Flow Field Ensembles. Independent of the representation,
errors of the simulation itself are often caused by inaccurate initial conditions,
limitations of the chosen simulation model, and numerical errors. To gain a better understanding
of the possible outcomes, multiple simulation runs can be calculated, resulting in
sets of simulation output referred to as ensembles. Of particular interest when studying the
material transport behavior of ensembles is the identification of areas where the simulation
runs agree or disagree. We introduce and evaluate an interactive method that enables application
scientists to reliably identify and examine regions of agreement and disagreement,
while taking into account the local transport behavior within individual simulation runs.
Particle-Based Representation and Visualization of Uncertain Flow Data Sets. Unlike
simulation ensembles, where uncertainty of the solution appears in the form of different
simulation runs, moment-based Eulerian multi-phase fluid simulations are probabilistic in
nature. These simulations, used in process engineering to simulate the behavior of bubbles in
liquid media, are aimed toward reducing the need for real-world experiments. The locations
of individual bubbles are not modeled explicitly, but stochastically through the properties of
locally defined bubble populations. Comparisons between simulation results and physical
experiments are difficult. We describe and analyze an approach that generates representative
sets of bubbles for moment-based simulation data. Using our approach, application scientists
can directly, visually compare simulation results and physical experiments.
The usage of sensors in modern technical systems and consumer products is in a rapid increase. This advancement can be characterized by two major factors, namely, the mass introduction of consumer oriented sensing devices to the market and the sheer amount of sensor data being generated. These characteristics raise subsequent challenges regarding both the consumer sensing devices' reliability and the management and utilization of the generated sensor data. This thesis addresses these challenges through two main contributions. It presents a novel framework that leverages sentiment analysis techniques in order to assess the quality of consumer sensing devices. It also couples semantic technologies with big data technologies to present a new optimized approach for realization and management of semantic sensor data, hence providing a robust means of integration, analysis, and reuse of the generated data. The thesis also presents several applications that show the potential of the contributions in real-life scenarios.
Due to the broad range, growing feature set and fast release pace of new sensor-based products, evaluating these products is very challenging as standard product testing is not practical. As an alternative, an end-to-end aspect-based sentiment summarizer pipeline for evaluation of consumer sensing devices is presented. The pipeline uses product reviews to extract the sentiment at the aspect level and includes several components namely, product name extractor, aspects extractor and a lexicon-based sentiment extractor which handles multiple sentiment analysis challenges such as sentiment shifters, negations, and comparative sentences among others. The proposed summarizer's components generally outperform the state-of-the-art approaches. As a use case, features of the market leading fitness trackers are evaluated and a dynamic visual summarizer is presented to display the evaluation results and to provide personalized product recommendations for potential customers.
The increased usage of sensing devices in the consumer market is accompanied with increased deployment of sensors in various other fields such as industry, agriculture, and energy production systems. This necessitates using efficient and scalable methods for storing and processing of sensor data. Coupling big data technologies with semantic techniques not only helps to achieve the desired storage and processing goals, but also facilitates data integration, data analysis, and the utilization of data in unforeseen future applications through preserving the data generation context. This thesis proposes an efficient and scalable solution for semantification, storage and processing of raw sensor data through ontological modelling of sensor data and a novel encoding scheme that harnesses the split between the statements of the conceptual model of an ontology (TBox) and the individual facts (ABox) along with in-memory processing capabilities of modern big data systems. A sample use case is further introduced where a smartphone is deployed in a transportation bus to collect various sensor data which is then utilized in detecting street anomalies.
In addition to the aforementioned contributions, and to highlight the potential use cases of sensor data publicly available, a recommender system is developed using running route data, used for proximity-based retrieval, to provide personalized suggestions for new routes considering the runner's performance, visual and nature of route preferences.
This thesis aims at enhancing the integration of sensing devices in daily life applications through facilitating the public acquisition of consumer sensing devices. It also aims at achieving better integration and processing of sensor data in order to enable new potential usage scenarios of the raw generated data.
Topological insulators (TI) are a fascinating new state of matter. Like usual insulators, their band structure possesses a band gap, such that they cannot conduct current in their bulk. However, they are able to conduct current along their edges and surfaces, due to edge states that cross the band gap. What makes TIs so interesting and potentially useful are these robust unidirectional edge currents. They are immune to significant defects and disorder, which means that they provide scattering-free transport.
In photonics, using topological protection has a huge potential for applications, e.g. for robust optical data transfer [1-3] – even on the quantum level [4, 5] – or to make devices more stable and robust [6, 7]. Therefore, the field of topological insulators has spread to optics to create the new and active research field of topological photonics [8-10].
Well-defined and controllable model systems can help to provide deeper insight into the mechanisms of topologically protected transport. These model systems provide a vast control over parameters. For example, arbitrary lattice types without defects can be examined, and single lattice sites can be manipulated. Furthermore, they allow for the observation of effects that usually happen at extremely short time-scales in solids. Model systems based on photonic waveguides are ideal candidates for this.
They consist of optical waveguides arranged on a lattice. Due to evanescent coupling, light that is inserted into one waveguide spreads along the lattice. This coupling of light between waveguides can be seen as an analogue to electrons hopping/tunneling between atomic lattice sites in a solid.
The theoretical basis for this analogy is given by the mathematical equivalence between Schrödinger and paraxial Helmholtz equation. This means that in these waveguide systems, the role of time is assigned to a spatial axis. The field evolution along the waveguides' propagation axis z thus models the temporal evolution of an electron's wave-function in solid states. Electric and magnetic fields acting on electrons in solids need to be incorporated into the photonic platform by introducing artificial fields. These artificial gauge fields need to act on photons in the same way that their electro-magnetic counterparts act on electrons. E.g., to create a photonic analogue of a topological insulator the waveguides are bent helically along their propagation axis to model the effect of a magnetic field [3]. This means that the fabrication of these waveguide arrays needs to be done in 3D.
In this thesis, a new method to 3D micro-print waveguides is introduced. The inverse structure is fabricated via direct laser writing, and subsequently infiltrated with a material with higher refractive index contrast. We will use these model systems of evanescently coupled waveguides to look at different effects in topological systems, in particular at Floquet topological systems.
We will start with a topologically trivial system, consisting of two waveguide arrays with different artificial gauge fields. There, we observe that an interface between these trivial gauge fields has a profound impact on the wave vector of the light traveling across it. We deduce an analog to Snell's law and verify it experimentally.
Then we will move on to Floquet topological systems, consisting of helical waveguides. At the interface between two Floquet topological insulators with opposite helicity of the waveguides, we find additional trivial interface modes that trap the light. This allows to investigate the interaction between trivial and topological modes in the lattice.
Furthermore, we address the question if topological edge states are robust under the influence of time-dependent defects. In a one-dimensional topological model (the Su-Schrieffer-Heeger model [11]) we apply periodic temporal modulations to an edge wave-guide. We find Floquet copies of the edge state, that couple to the bulk in a certain frequency window and thus depopulate the edge state.
In the two-dimensional Floquet topological insulator, we introduce single defects at the edge. When these defects share the temporal periodicity of the helical bulk waveguides, they have no influence on a topological edge mode. Then, the light moves around/through the defect without being scattered into the bulk. Defects with different periodicity, however, can – likewise to the defects in the SSH model – induce scattering of the edge state into the bulk.
In the end we will briefly highlight a newly emerging method for the fabrication of waveguides with low refractive index contrast. Moreover, we will introduce new ways to create artificial gauge fields by the use of orbital angular momentum states in waveguides.