Filtern
Volltext vorhanden
- ja (136) (entfernen)
Erscheinungsjahr
- 2016 (136) (entfernen)
Dokumenttyp
- Dissertation (136) (entfernen)
Sprache
- Englisch (96)
- Deutsch (36)
- Spanisch (2)
- Französisch (1)
- Italienisch (1)
Gehört zur Bibliographie
- ja (136)
Schlagworte
- Klimawandel (4)
- climate change (4)
- Blickbewegungen (3)
- earthquake (3)
- Aggression (2)
- Aphasie (2)
- Berlin (2)
- Bodenfeuchte (2)
- Centrosom (2)
- Deutschland (2)
Institut
- Institut für Geowissenschaften (26)
- Institut für Chemie (18)
- Institut für Biochemie und Biologie (13)
- Institut für Physik und Astronomie (12)
- Department Linguistik (8)
- Department Sport- und Gesundheitswissenschaften (7)
- Institut für Ernährungswissenschaft (7)
- Institut für Mathematik (7)
- Wirtschaftswissenschaften (7)
- Department Psychologie (6)
Variations in the distribution of mass within an orogen may lead to transient sediment storage, which in turn might affect the state of stress and the level of fault activity. Distinguishing between different forcing mechanisms causing variations of sediment flux and tectonic activity, is therefore one of the most challenging tasks in understanding the spatiotemporal evolution of active mountain belts.
The Himalayan mountain belt is one of the most significant Cenozoic collisional mountain belt, formed due to collision between northward-bound Indian Plate and the Eurasian Plate during the last 55-50 Ma. Ongoing convergence of these two tectonic plates is accommodated by faulting and folding within the Himalayan arc-shaped orogen and the continued lateral and vertical growth of the Tibetan Plateau and mountain belts adjacent to the plateau as well as regions farther north. Growth of the Himalayan orogen is manifested by the development of successive south-vergent thrust systems. These thrust systems divide the orogen into different morphotectonic domains. From north to south these thrusts are the Main Central Thrust (MCT), the Main Boundary Thrust (MBT) and the Main Frontal Thrust (MFT). The growing topography interacts with moisture-bearing monsoonal winds, which results in pronounced gradients in rainfall, weathering, erosion and sediment transport toward the foreland and beyond. However, a fraction of this sediment is trapped and transiently stored within the intermontane valleys or ‘dun’s within the lower-elevation foothills of the range. Improved understanding of the spatiotemporal evolution of these sediment archives could provide a unique opportunity to decipher the triggers of variations in sediment production, delivery and storage in an actively deforming mountain belt and support efforts to test linkages between sediment volumes in intermontane basins and changes in the shallow crustal stress field. As sediment redistribution in mountain belts on timescales of 102-104 years can effect cultural characteristics and infrastructure in the intermontane valleys and may even impact the seismotectonics of a mountain belt, there is a heightened interest in understanding sediment-routing processes and causal relationships between tectonism, climate and topography. It is here at the intersection between tectonic processes and superposed climatic and sedimentary processes in the Himalayan orogenic wedge, where my investigation is focused on. The study area is the intermontane Kangra Basin in the northwestern Sub-Himalaya, because the characteristics of the different Himalayan morphotectonic provinces are well developed, the area is part of a region strongly influenced by monsoonal forcing, and the existence of numerous fluvial terraces provides excellent strain markers to assess deformation processes within the Himalayan orogenic wedge. In addition, being located in front of the Dhauladhar Range the region is characterized by pronounced gradients in past and present-day erosion and sediment processes associated with repeatedly changing climatic conditions. In light of these conditions I analysed climate-driven late Pleistocene-Holocene sediment cycles in this tectonically active region, which may be responsible for triggering the tectonic re-organization within the Himalayan orogenic wedge, leading to out-of-sequence thrusting, at least since early Holocene.
The Kangra Basin is bounded by the MBT and the Sub-Himalayan Jwalamukhi Thrust (JMT) in the north and south, respectively and transiently stores sediments derived from the Dhauladhar Range. The Basin contains ~200-m-thick conglomerates reflecting two distinct aggradation phases; following aggradation, several fluvial terraces were sculpted into these fan deposits. 10Be CRN surface exposure dating of these terrace levels provides an age of 53.4±3.2 ka for the highest-preserved terrace (AF1); subsequently, this surface was incised until ~15 ka, when the second fan (AF2) began to form. AF2 fan aggradation was superseded by episodic Holocene incision, creating at least four terrace levels. We find a correlation between variations in sediment transport and ∂18O records from regions affected by the Indian Summer Monsoon (ISM). During strengthened ISMs sand post-LGM glacial retreat, aggradation occurred in the Kangra Basin, likely due to high sediment flux, whereas periods of a weakened ISM coupled with lower sediment supply coincided with renewed re-incision.
However, the evolution of fluvial terraces along Sub-Himalayan streams in the Kangra sector is also forced by tectonic processes. Back-tilted, folded terraces clearly document tectonic activity of the JMT. Offset of one of the terrace levels indicates a shortening rate of 5.6±0.8 to 7.5±1.0 mm.a-1 over the last ~10 ka. Importantly, my study reveals that late Pleistocene/Holocene out-of-sequence thrusting accommodates 40-60% of the total 14±2 mm.a-1 shortening partitioned throughout the Sub-Himalaya. Importantly, the JMT records shortening at a lower rate over longer timescales hints towards out-of-sequence activity within the Sub-Himalaya. Re-activation of the JMT could be related to changes in the tectonic stress field caused by large-scale sediment removal from the basin. I speculate that the deformation processes of the Sub-Himalaya behave according to the predictions of critical wedge model and assume the following: While >200m of sediment aggradation would trigger foreland-ward propagation of the deformation front, re-incision and removal of most of the stored sediments (nearly 80-85% of the optimum basin-fill) would again create a sub-critical condition of the wedge taper and trigger the retreat of the deformation front.
While tectonism is responsible for the longer-term processes of erosion associated with steepening hillslopes, sediment cycles in this environment are mainly the result of climatic forcing. My new 10Be cosmogenic nuclide exposure dates and a synopsis of previous studies show the late Pleistocene to Holocene alluvial fills and fluvial terraces studied here record periodic fluctuations of sediment supply and transport capacity on timescales of 1000-100000 years. To further evaluate the potential influence of climate change on these fluctuations, I compared the timing of aggradation and incision phases recorded within remnant alluvial fans and terraces with continental climate archives such as speleothems in neighboring regions affected by monsoonal precipitation. Together with previously published OSL ages yielding the timing of aggradation, I find a correlation between variations in sediment transport with oxygen-isotope records from regions affected by the Indian Summer Monsoon (ISM). Accordingly, during periods of increased monsoon intensity (transitions from dry and cold to wet and warm periods – MIS4 to MIS3 and MIS2 to MIS1) (MIS=marine isotope stage) and post-Last Glacial Maximum glacial retreat, aggradation occurred in the Kangra Basin, likely due to high sediment flux. Conversely, periods of weakened monsoon intensity or lower sediment supply coincide with re-incision of the existing basin-fill.
Finally, my study entails part of a low-temperature thermochronology study to assess the youngest exhumation history of the Dhauladhar Range. Zircon helium (ZHe) ages and existing low-temperature data sets (ZHe, apatite fission track (AFT)) across this range, together with 3D thermokinematic modeling (PECUBE) reveals constraints on exhumation and activity of the range-bounding Main Boundary Thrust (MBT) since at least mid-Miocene time. The modeling results indicate mean slip rates on the MBT-fault ramp of ~2 – 3 mm.a-1 since its activation. This has lead to the growth of the >5-km-high frontal Dhauladhar Range and continuous deep-seated exhumation and erosion. The obtained results also provide interesting constraints of deformation patterns and their variation along strike. The results point towards the absence of the time-transient ‘mid-crustal ramp’ in the basal decollement and
duplexing of the Lesser Himalayan sequence, unlike the nearby regions or even the central Nepal domain. A fraction of convergence (~10-15%) is accommodated along the deep-seated MBT-ramp, most likely merging into the MHT. This finding is crucial for a rigorous assessment of the overall level of tectonic activity in the Himalayan morphotectonic provinces as it contradicts recently-published geodetic shortening estimates. In these studies, it has been proposed that the total Himalayan shortening in the NW Himalaya is accommodated within the Sub-Himalaya whereas no tectonic activity is assigned to the MBT.
Services that operate over the Internet are under constant threat of being exposed to fraudulent use. Maintaining good user experience for legitimate users often requires the classification of entities as malicious or legitimate in order to initiate countermeasures. As an example, inbound email spam filters decide for spam or non-spam. They can base their decision on both the content of each email as well as on features that summarize prior emails received from the sending server. In general, discriminative classification methods learn to distinguish positive from negative entities. Each decision for a label may be based on features of the entity and related entities. When labels of related entities have strong interdependencies---as can be assumed e.g. for emails being delivered by the same user---classification decisions should not be made independently and dependencies should be modeled in the decision function. This thesis addresses the formulation of discriminative classification problems that are tailored for the specific demands of the following three Internet security applications. Theoretical and algorithmic solutions are devised to protect an email service against flooding of user inboxes, to mitigate abusive usage of outbound email servers, and to protect web servers against distributed denial of service attacks.
In the application of filtering an inbound email stream for unsolicited emails, utilizing features that go beyond each individual email's content can be valuable. Information about each sending mail server can be aggregated over time and may help in identifying unwanted emails. However, while this information will be available to the deployed email filter, some parts of the training data that are compiled by third party providers may not contain this information. The missing features have to be estimated at training time in order to learn a classification model. In this thesis an algorithm is derived that learns a decision function that integrates over a distribution of values for each missing entry. The distribution of missing values is a free parameter that is optimized to learn an optimal decision function.
The outbound stream of emails of an email service provider can be separated by the customer IDs that ask for delivery. All emails that are sent by the same ID in the same period of time are related, both in content and in label. Hijacked customer accounts may send batches of unsolicited emails to other email providers, which in turn might blacklist the sender's email servers after detection of incoming spam emails. The risk of being blocked from further delivery depends on the rate of outgoing unwanted emails and the duration of high spam sending rates. An optimization problem is developed that minimizes the expected cost for the email provider by learning a decision function that assigns a limit on the sending rate to customers based on the each customer's email stream.
Identifying attacking IPs during HTTP-level DDoS attacks allows to block those IPs from further accessing the web servers. DDoS attacks are usually carried out by infected clients that are members of the same botnet and show similar traffic patterns. HTTP-level attacks aim at exhausting one or more resources of the web server infrastructure, such as CPU time. If the joint set of attackers cannot increase resource usage close to the maximum capacity, no effect will be experienced by legitimate users of hosted web sites. However, if the additional load raises the computational burden towards the critical range, user experience will degrade until service may be unavailable altogether. As the loss of missing one attacker depends on block decisions for other attackers---if most other attackers are detected, not blocking one client will likely not be harmful---a structured output model has to be learned. In this thesis an algorithm is developed that learns a structured prediction decoder that searches the space of label assignments, guided by a policy.
Each model is evaluated on real-world data and is compared to reference methods. The results show that modeling each classification problem according to the specific demands of the task improves performance over solutions that do not consider the constraints inherent to an application.
Understanding the role of natural climate variability under the pressure of human induced changes of climate and landscapes, is crucial to improve future projections and adaption strategies. This doctoral thesis aims to reconstruct Holocene climate and environmental changes in NE Germany based on annually laminated lake sediments. The work contributes to the ICLEA project (Integrated CLimate and Landscape Evolution Analyses). ICLEA intends to compare multiple high-resolution proxy records with independent chronologies from the N central European lowlands, in order to disentangle the impact of climate change and human land use on landscape development during the Lateglacial and Holocene. In this respect, two study sites in NE Germany are investigated in this doctoral project, Lake Tiefer See and palaeolake Wukenfurche. While both sediment records are studied with a combination of high-resolution sediment microfacies and geochemical analyses (e.g. µ-XRF, carbon geochemistry and stable isotopes), detailed proxy understanding mainly focused on the continuous 7.7 m long sediment core from Lake Tiefer See covering the last ~6000 years. Three main objectives are pursued at Lake Tiefer See: (1) to perform a reliable and independent chronology, (2) to establish microfacies and geochemical proxies as indicators for climate and environmental changes, and (3) to trace the effects of climate variability and human activity on sediment deposition.
Addressing the first aim, a reliable chronology of Lake Tiefer See is compiled by using a multiple-dating concept. Varve counting and tephra findings form the chronological framework for the last ~6000 years. The good agreement with independent radiocarbon dates of terrestrial plant remains verifies the robustness of the age model. The resulting reliable and independent chronology of Lake Tiefer See and, additionally, the identification of nine tephras provide a valuable base for detailed comparison and synchronization of the Lake Tiefer See data set with other climate records. The sediment profile of Lake Tiefer See exhibits striking alternations between well-varved and non-varved sediment intervals. The combination of microfacies, geochemical and microfossil (i.e. Cladocera and diatom) analyses indicates that these changes of varve preservation are caused by variations of lake circulation in Lake Tiefer See. An exception is the well-varved sediment deposited since AD 1924, which is mainly influenced by human-induced lake eutrophication. Well-varved intervals before the 20th century are considered to reflect phases of reduced lake circulation and, consequently, stronger anoxic conditions. Instead, non-varved intervals indicate increased lake circulation in Lake Tiefer See, leading to more oxygenated conditions at the lake ground. Furthermore, lake circulation is not only influencing sediment deposition, but also geochemical processes in the lake. As, for example, the proxy meaning of δ13COM varies in time in response to changes of the oxygen regime in the lake hypolinion. During reduced lake circulation and stronger anoxic conditions δ13COM is influenced by microbial carbon cycling. In contrast, organic matter degradation controls δ13COM during phases of intensified lake circulation and more oxygenated conditions. The varve preservation indicates an increasing trend of lake circulation at Lake Tiefer See after ~4000 cal a BP. This trend is superimposed by decadal to centennial scale variability of lake circulation intensity. Comparison to other records in Central Europe suggests that the long-term trend is probably related to gradual changes in Northern Hemisphere orbital forcing, which induced colder and windier conditions in Central Europe and, therefore, reinforced lake circulation. Decadal to centennial scale periods of increased lake circulation coincide with settlement phases at Lake Tiefer See, as inferred from pollen data of the same sediment record. Deforestation reduced the wind shelter of the lake, which probably increased the sensitivity of lake circulation to wind stress. However, results of this thesis also suggest that several of these phases of increased lake circulation are additionally reinforced by climate changes. A first indication is provided by the comparison to the Baltic Sea record, which shows striking correspondence between major non-varved intervals at Lake Tiefer See and bioturbated sediments in the Baltic Sea. Furthermore, a preliminary comparison to the ICLEA study site Lake Czechowskie (N central Poland) shows a coincidence of at least three phases of increased lake circulation in both lakes, which concur with periods of known climate changes (2.8 ka event, ’Migration Period’ and ’Little Ice Age’). These results suggest an additional over-regional climate forcing also on short term increased of lake circulation in Lake Tiefer See.
In summary, the results of this thesis suggest that lake circulation at Lake Tiefer See is driven by a combination of long-term and short-term climate changes as well as of anthropogenic deforestation phases. Furthermore, the lake circulation drives geochemical cycles in the lake affecting the meaning of proxy data. Therefore, the work presented here expands the knowledge of climate and environmental variability in NE Germany. Furthermore, the integration of the Lake Tiefer See multi-proxy record in a regional comparison with another ICLEA side, Lake Czechowskie, enabled to better decipher climate changes and human impact on the lake system. These first results suggest a huge potential for further detailed regional comparisons to better understand palaeoclimate dynamics in N central Europe.
Die vorgelegte Dissertation präsentiert wissenschaftliche Ergebnisse, die in der Zeit vom Dezember 2012 bis August 2016, erarbeitet wurden. Der zentrale Inhalt der Arbeit ist die Simulation von Röntgenabsorptionsprozessen von verschiedenen Systemen in kondensierter Phase. Genauer gesagt, werden Nahkantenabsorptions- (NEXAFS) sowie Röntgenphotoelektronenspektren (XPS) berechnet. In beiden Fällen wird ein Röntgenphoton von einem molekularen System absorbiert. Aufgrund der hohen Photonenenergie wird ein stark gebundenes kernnahes Elektron angeregt. Bei der XPS gelangt dieses mit einer zu messenden kinetischen Energie in Kontinuumszustände. In Abhängigkeit der eingestrahlten Photonenenergie und der kinetischen Energie des austreten Elektrons, kann die Bindungsenergie berechnet werden, welche die zentrale Größe der XPS ist. Im Falle der NEXAFS-Spektroskopie wird das kernnahe Elektron in unbesetzte gebundene Zustände angeregt. Die zentrale Größe ist die Absorption als Funktion der eingestrahlten Photonenenergie. Das erste Kapitel meiner Arbeit erörtert detailliert die experimentellen Methoden sowie die daraus gewonnenen charakteristischen Größen.
Die experimentellen Spektren zeigen oft viele Resonanzen, deren Interpretation aufgrund fehlender Referenzmaterialien schwierig ist. In solchen Fällen bietet es sich an, die Spektren mittels quantenchemischer Methoden zu simulieren. Der dafür erforderliche mathematisch-physikalische Methodenkatalog wird im zweiten Kapitel der Arbeit erörtert.
Das erste von mir untersuchte System ist Graphen. In experimentellen Arbeiten wurde die Oberfläche mittels Bromplasma modifiziert. Die im Anschluss gemessenen NEXAFS-Spektren unterscheiden sich maßgeblich von den Spektren der unbehandelten Oberfläche. Mithilfe periodischer DFT-Rechnungen wurden verschiedene Gitterdefekte sowie bromierte Systeme untersucht und die NEXAFS-Spektren simuliert. Mittels der Simulationen können die Beiträge verschiedener Anregungszentren analysiert werden. Die Berechnungen erlauben den Schluss, dass Gitterdefekte maßgeblich für die entstandenen Veränderungen verantwortlich sind.
Polyvinylalkohol (PVA) wurde als zweites System behandelt. Hierbei sollte untersucht werden, wie groß der Einfluss der Molekularbewegung auf die Verbreiterung der Peaks im XP-Spektrum ist. Des Weiteren wurde untersucht, wie groß der Einfluss von intermolekularen Wechselwirkungen auf die Peakpositionen und Peakverbreiterung ist. Für die Berechnung dieses Systems wurde eine Kombination aus molekulardynamischen und quantenchemischen Methoden verwendet. Als Strukturen dienten Oligomermodelle, die unter dem Einfluss eines (ab initio) Potentials propagiert wurden. Entlang der erstellten Trajektorie wurden Schnappschüsse der Geometrien extrahiert und für die Berechnung der XP-Spektren verwendet. Die Spektren werden bereits mithilfe klassischer Molekulardynamik sehr gut reproduziert. Die erhaltenen Peakbreiten sind verglichen mit dem Experiment allerdings zu klein. Die Hauptursache der Peakverbreiterung ist die Molekularbewegung. Intermolekulare Wechselwirkungen verschieben die Peakpositionen um 0.6 eV zu kleineren Anregungsenergien.
Im dritten Teil der Arbeit stehen die NEXAFS-Spektren von ionischen Flüssigkeiten (ILs) im Fokus. Die experimentell gefundenen Spektren zeigen eine komplexe Struktur mit vielen Resonanzen. In der Arbeit wurden zwei ILs untersucht. Als Geometrien verwenden wir Clustermodelle, die aus experimentellen Kristallstrukturen extrahiert wurden. Die berechneten Spektren erlauben es, die Resonanzen den Anregungszentren zuzuordnen. Außerdem kann eine erstmals gemessene Doppelresonanz simuliert und erklärt werden. Insgesamt kann die Interpretation der Spektren mithilfe der Simulation signifikant erweitert werden.
In allen Systemen wurde zur Berechnung des NEXAFS-Spektrums eine auf Dichtefunktionaltheorie basierende Methode verwendet (die sogenannte Transition-Potential Methode). Gängige wellenfunktionsbasierte Methoden, wie die Konfigurationswechselwirkung mit Einfachanregungen (CIS), zeigen eine starke Blauverschiebung, wenn als Referenz eine Hartree-Fock Slaterdeterminante verwendet wird. Wir zeigen, dass die Verwendung von kernnah-angeregten Determinanten sowohl das resultierende Spektrum als auch die Anregungsenergien deutlich verbessert. Des Weiteren werden auch Referenzen aus Dichtefunktionalrechnungen getestet. Zusätzlich werden auch Referenzen mit gebrochenen Besetzungszahlen für kernnahe Elektronen verwendet. In der Arbeit werden die Resultate der verschiedenen Referenzen miteinander verglichen. Es zeigt sich, dass Referenzen mit gebrochenen Besetzungszahlen das Spektrum nicht weiter verbessern. Der Einfluss der verwendeten Elektronenstrukturmethode ist eher gering.
Background: Low back pain (LBP) is one of the world wide leading causes of limited activity and disability. Impaired motor control has been found to be one of the possible factors related to the development or persistence of LBP. In particularly, motor control strategies seemed to be altered in situations requiring reactive responses of the trunk counteracting sudden external forces. However, muscular responses were mostly assessed in (quasi) static testing situations under simplified laboratory conditions. Comprehensive investigations in motor control strategies during dynamic everyday situations are lacking. The present research project aimed to investigate muscular compensation strategies following unexpected gait perturbations in people with and without LBP. A novel treadmill stumbling protocol was tested for its validity and reliability to provoke muscular reflex responses at the trunk and the lower extremities (study 1). Thereafter, motor control strategies in response to sudden perturbations were compared between people with LBP and asymptomatic controls (CTRL) (study 2). In accordance with more recent concepts of motor adaptation to pain, it was hypothesized that pain may have profound consequences on motor control strategies in LBP. Therefore, it was investigated whether differences in compensation strategies were either consisting of changes local to the painful area at the trunk, or also being present in remote areas such as at the lower extremities.
Methods: All investigations were performed on a custom build split-belt treadmill simulating trip-like events by unexpected rapid deceleration impulses (amplitude: 2 m/s; duration: 100 ms; 200 ms after heel contact) at 1m/s baseline velocity. A total number of 5 (study 1) and 15 (study 2) right sided perturbations were applied during walking trials. Muscular activities were assessed by surface electromyography (EMG), recorded at 12 trunk muscles and 10 (study 1) respectively 5 (study 2) leg muscles. EMG latencies of muscle onset [ms] were retrieved by a semi-automatic detection method. EMG amplitudes (root mean square (RMS)) were assessed within 200 ms post perturbation, normalized to full strides prior to any perturbation [RMS%]. Latency and amplitude investigations were performed for each muscle individually, as well as for pooled data of muscles grouped by location. Characteristic pain intensity scores (CPIS; 0-100 points, von Korff) based on mean intensity ratings reported for current, worst and average pain over the last three months were used to allocate participants into LBP (≥30 points) or CTRL (≤10 points). Test-retest reproducibility between measurements was determined by a compilation of measures of reliability. Differences in muscular activities between LBP and CTRL were analysed descriptively for individual muscles; differences based on grouped muscles were statistically tested by using a multivariate analysis of variance (MANOVA, α =0.05).
Results: Thirteen individuals were included into the analysis of study 1. EMG latencies revealed reflex muscle activities following the perturbation (mean: 89 ms). Respective EMG amplitudes were on average 5-fold of those assessed in unperturbed strides, though being characterized by a high inter-subject variability. Test-retest reliability of muscle latencies showed a high reproducibility, both for muscles at the trunk and legs. In contrast, reproducibility of amplitudes was only weak to moderate for individual muscles, but increased when being assessed as a location specific outcome summary of grouped muscles. Seventy-six individuals were eligible for data analysis in study 2. Group allocation according to CPIS resulted in n=25 for LBP and n=29 for CTRL. Descriptive analysis of activity onsets revealed longer delays for all muscles within LBP compared to CTRL (trunk muscles: mean 10 ms; leg muscles: mean 3 ms). Onset latencies of grouped muscles revealed statistically significant differences between LBP and CTRL for right (p=0.009) and left (p=0.007) abdominal muscle groups. EMG amplitude analysis showed a high variability in activation levels between individuals, independent of group assignment or location. Statistical testing of grouped muscles indicated no significant difference in amplitudes between LBP and CTRL.
Discussion: The present research project could show that perturbed treadmill walking is suitable to provoke comprehensive reflex responses at the trunk and lower extremities, both in terms of sudden onsets and amplitudes of reflex activity. Moreover, it could demonstrate that sudden loadings under dynamic conditions provoke an altered reflex timing of muscles surrounding the trunk in people with LBP compared to CTRL. In line with previous investigations, compensation strategies seemed to be deployed in a task specific manner, with differences between LBP and CTRL being evident predominately at ventral sides. No muscular alterations exceeding the trunk could be found when being assessed under the automated task of locomotion. While rehabilitation programs tailored towards LBP are still under debate, it is tempting to urge the implementation of dynamic sudden loading incidents of the trunk to enhance motor control and thereby to improve spinal protection. Moreover, in respect to the consistently observed task specificity of muscular compensation strategies, such a rehabilitation program should be rich in variety.
In experiments investigating sentence processing, eye movement measures such as fixation durations and regression proportions while reading are commonly used to draw conclusions about processing difficulties. However, these measures are the result of an interaction of multiple cognitive levels and processing strategies and thus are only indirect indicators of processing difficulty. In order to properly interpret an eye movement response, one has to understand the underlying principles of adaptive processing such as trade-off mechanisms between reading speed and depth of comprehension that interact with task demands and individual differences. Therefore, it is necessary to establish explicit models of the respective mechanisms as well as their causal relationship with observable behavior. There are models of lexical processing and eye movement control on the one side and models on sentence parsing and memory processes on the other. However, no model so far combines both sides with explicitly defined linking assumptions.
In this thesis, a model is developed that integrates oculomotor control with a parsing mechanism and a theory of cue-based memory retrieval. On the basis of previous empirical findings and independently motivated principles, adaptive, resource-preserving mechanisms of underspecification are proposed both on the level of memory access and on the level of syntactic parsing. The thesis first investigates the model of cue-based retrieval in sentence comprehension of Lewis & Vasishth (2005) with a comprehensive literature review and computational modeling of retrieval interference in dependency processing. The results reveal a great variability in the data that is not explained by the theory. Therefore, two principles, 'distractor prominence' and 'cue confusion', are proposed as an extension to the theory, thus providing a more adequate description of systematic variance in empirical results as a consequence of experimental design, linguistic environment, and individual differences. In the remainder of the thesis, four interfaces between parsing and eye movement control are defined: Time Out, Reanalysis, Underspecification, and Subvocalization. By comparing computationally derived predictions with experimental results from the literature, it is investigated to what extent these four interfaces constitute an appropriate elementary set of assumptions for explaining specific eye movement patterns during sentence processing. Through simulations, it is shown how this system of in itself simple assumptions results in predictions of complex, adaptive behavior.
In conclusion, it is argued that, on all levels, the sentence comprehension mechanism seeks a balance between necessary processing effort and reading speed on the basis of experience, task demands, and resource limitations. Theories of linguistic processing therefore need to be explicitly defined and implemented, in particular with respect to linking assumptions between observable behavior and underlying cognitive processes. The comprehensive model developed here integrates multiple levels of sentence processing that hitherto have only been studied in isolation. The model is made publicly available as an expandable framework for future studies of the interactions between parsing, memory access, and eye movement control.
In the past, floods were basically managed by flood control mechanisms. The focus was set on the reduction of flood hazard. The potential consequences were of minor interest. Nowadays river flooding is increasingly seen from the risk perspective, including possible consequences. Moreover, the large-scale picture of flood risk became increasingly important for disaster management planning, national risk developments and the (re-) insurance industry. Therefore, it is widely accepted that risk-orientated flood management ap-proaches at the basin-scale are needed. However, large-scale flood risk assessment methods for areas of several 10,000 km² are still in early stages. Traditional flood risk assessments are performed reach wise, assuming constant probabilities for the entire reach or basin. This might be helpful on a local basis, but where large-scale patterns are important this approach is of limited use. Assuming a T-year flood (e.g. 100 years) for the entire river network is unrealistic and would lead to an overestimation of flood risk at the large scale. Due to the lack of damage data, additionally, the probability of peak discharge or rainfall is usually used as proxy for damage probability to derive flood risk. With a continuous and long term simulation of the entire flood risk chain, the spatial variability of probabilities could be consider and flood risk could be directly derived from damage data in a consistent way.
The objective of this study is the development and application of a full flood risk chain, appropriate for the large scale and based on long term and continuous simulation. The novel approach of ‘derived flood risk based on continuous simulations’ is introduced, where the synthetic discharge time series is used as input into flood impact models and flood risk is directly derived from the resulting synthetic damage time series.
The bottleneck at this scale is the hydrodynamic simu-lation. To find suitable hydrodynamic approaches for the large-scale a benchmark study with simplified 2D hydrodynamic models was performed. A raster-based approach with inertia formulation and a relatively high resolution of 100 m in combination with a fast 1D channel routing model was chosen.
To investigate the suitability of the continuous simulation of a full flood risk chain for the large scale, all model parts were integrated into a new framework, the Regional Flood Model (RFM). RFM consists of the hydrological model SWIM, a 1D hydrodynamic river network model, a 2D raster based inundation model and the flood loss model FELMOps+r. Subsequently, the model chain was applied to the Elbe catchment, one of the largest catchments in Germany. For the proof-of-concept, a continuous simulation was per-formed for the period of 1990-2003. Results were evaluated / validated as far as possible with available observed data in this period. Although each model part introduced its own uncertainties, results and runtime were generally found to be adequate for the purpose of continuous simulation at the large catchment scale.
Finally, RFM was applied to a meso-scale catchment in the east of Germany to firstly perform a flood risk assessment with the novel approach of ‘derived flood risk assessment based on continuous simulations’. Therefore, RFM was driven by long term synthetic meteorological input data generated by a weather generator. Thereby, a virtual time series of climate data of 100 x 100 years was generated and served as input to RFM providing subsequent 100 x 100 years of spatially consistent river discharge series, inundation patterns and damage values. On this basis, flood risk curves and expected annual damage could be derived directly from damage data, providing a large-scale picture of flood risk. In contrast to traditional flood risk analysis, where homogenous return periods are assumed for the entire basin, the presented approach provides a coherent large-scale picture of flood risk. The spatial variability of occurrence probability is respected. Additionally, data and methods are consistent. Catchment and floodplain processes are repre-sented in a holistic way. Antecedent catchment conditions are implicitly taken into account, as well as physical processes like storage effects, flood attenuation or channel–floodplain interactions and related damage influencing effects. Finally, the simulation of a virtual period of 100 x 100 years and consequently large data set on flood loss events enabled the calculation of flood risk directly from damage distributions. Problems associated with the transfer of probabilities in rainfall or peak runoff to probabilities in damage, as often used in traditional approaches, are bypassed.
RFM and the ‘derived flood risk approach based on continuous simulations’ has the potential to provide flood risk statements for national planning, re-insurance aspects or other questions where spatially consistent, large-scale assessments are required.
Diese Arbeit befasst sich mit der Herstellung und Charakterisierung von thermoresponsiven Filmen auf Goldelektroden durch Fixierung eines bereits synthetisierten thermoresponsiven Polymers. Als Basis für die Entwicklung der responsiven Grenzfläche dienten drei unterschiedliche Copolymere (Polymere I, II und III) aus der Gruppe der thermisch schaltbaren Poly(oligo(ethylenglykol)methacrylate).
Die turbidimetrischen Messungen der Copolymere in Lösungen haben gezeigt, dass der Trübungspunkt vom pH-Wert, der Gegenwart von Salzen sowie von der Ionenstärke der Lösung abhängig ist. Nach der Charakterisierung der Polymere in Lösung wurden Experimente der kovalenten Kopplung der Polymere I bis III an die Oberfläche der Gold-Elektroden durchgeführt. Während bei Polymeren I und II die Ankopplung auf einer Amidverbrückung basierte, wurde bei Polymer III als alternative Methode zur Immobilisierung eine photoinduzierte Anbindung unter gleichzeitiger Vernetzung gewählt. Der Nachweis der erfolgreichen Ankopplung erfolgte bei allen Polymeren elektrochemisch mittels Cyclovoltammetrie und Impedanzspektroskopie in K3/4[Fe(CN)6]-Lösungen. Wie die Ellipsometrie-Messungen zeigten, waren die erhaltenen Polymer-Filme unterschiedlich dick. Die Ankopplung über Amidverbrückung lieferte dünne Filme (10 – 15 nm), während der photovernetzte Film deutlich dicker war (70-80 nm) und die darunter liegende Oberfläche relativ gut isolierte.
Elektrochemische Temperaturexperimente an Polymer-modifizierten Oberflächen in Lösungen in Gegenwart von K3/4[Fe(CN)6] zeigten, dass auch die immobilisierten Polymere I bis III responsives Temperaturverhalten zeigen. Bei Elektroden mit den immobilisierten Polymeren I und II ist der Temperaturverlauf der Parameterwerte diskontinuierlich – ab einem kritischen Punkt (37 °C für Polymer I und 45 °C für Polymer II) wird zunächst langsame Zunahme der Peakströme wird deutlich schneller. Das Temperaturverhalten von Polymer III ist dagegen bis 50 °C kontinuierlich, der Peakstrom sinkt hier durchgehend.
Weiterhin wurde mit den auf Polymeren II und III basierten Elektroden deren Anwendung als responsive Matrix für Bioerkennungsreaktionen untersucht. Es wurde die Ankopplung von kleinen Biorezeptoren, TAG-Peptiden, an Polymer II- und Polymer III-modifizierten Elektroden durchgeführt. Das hydrophile FLAG-TAG-Peptid verändert das Temperaturverhalten des Polymer II-Films unwesentlich, da es die Hydrophilie des Netzwerkes nicht beeinflusst. Weiterhin wurde der Effekt der Ankopplung der ANTI-FLAG-TAG-Antikörper an FLAG-TAG-modifizierte Polymer II-Filme untersucht. Es konnte gezeigt werden, dass die Antikörper spezifisch an FLAG-TAG-modifiziertes Polymer II binden. Es wurde keine unspezifische Anbindung von ANTI-FLAG-TAG an Polymer II beobachtet. Die Temperaturexperimente haben gezeigt, dass die thermische Restrukturierung des Polymer II-FLAG-TAG-Filmes auch nach der Antikörper-Ankopplung noch stattfindet. Der Einfluss der ANTI-FLAG-TAG-Ankopplung ist gering, da der Unterschied in der Hydrophilie zwischen Polymer II und FLAG-TAG bzw. ANTI-FLAG-TAG zu gering ist.
Für die Untersuchungen mit Polymer III-Elektroden wurde neben dem hydrophilen FLAG-TAG-Peptid das deutlich hydrophobere HA-TAG-Peptid ausgewählt. Wie im Falle der Polymer II Elektrode beeinflusst das gekoppelte FLAG-TAG-Peptid das Temperaturverhalten des Polymer III-Netzwerkes nur geringfügig. Die gemessenen Stromwerte sind geringer als bei der Polymer III-Elektrode. Das Temperaturverhalten der FLAG-TAG-Elektrode ähnelt dem der reinen Polymer III-Elektrode – die Stromwerte sinken kontinuierlich bis die Temperatur von ca. 40 °C erreicht ist, bei der ein Plateau beobachtet wird. Offensichtlich verändert FLAG-TAG auch in diesem Fall nicht wesentlich die Hydrophilie des Polymer III-Netzwerkes. Das an Polymer III-Elektroden gekoppelte hydrophobe HA-TAG-Peptid beeinflusst dagegen im starken Maße den Quellzustand des Netzwerkes. Die Ströme für die HA-TAG-Elektroden sind deutlich geringer als die für die FLAG-TAG-Polymer III-Elektroden, was auf geringeren Wassergehalt und dickeren Film zurückzuführen ist. Bereits ab 30 °C erfolgt der Anstieg von Stromwerten, der bei Polymer III- bzw. bei Polymer III-FLAG-TAG-Elektroden nicht beobachtet werden kann. Das gekoppelte hydrophobe HA-TAG-Peptid verdrängt Wasser aus dem Polymer III-Netzwerk, was in der Stauchung des Films bereits bei Raumtemperatur resultiert. Dies führt dazu, dass der Film im Laufe des Temperaturanstieges kaum noch komprimiert. Die Stromwerte steigen in diesem Fall entsprechend des Anstiegs der temperaturabhängigen Diffusion des Redoxpaares. Diese Untersuchungen zeigen, dass das HA-TAG-Peptid als Ankermolekül deutlich besser für eine potentielle Verwendung der Polymer III-Filme für sensorische Zwecke geeignet ist, da es sich deutlich in der Hydrophilie von Polymer III unterscheidet.
Solar-like stars maintain their magnetic fields thanks to a dynamo mechanism. The Babcock-Leighton dynamo is one possible dynamo that has the particularity to require magnetic flux tubes. Magnetic flux tubes are assumed to form at the bottom of the convective zone and rise buoyantly to the surface. A delayed dynamo model has been suggested, where the delay accounts for the rise time of the magnetic flux tubes; a time, that has been ignored by former studies.
The present thesis aims to study the applicability of the flux tube/Babcock-Leighton dynamo to other stars. To do so, we attempt to constrain the rise time of magnetic flux tubes thanks to the first fully compressible MHD simulations of rising magnetic flux tubes in stratified rotating spherical shells.
Such simulations are limited to an unrealistic parameter space, therefore, a scaling relation is required to scale the results to realistic physical regimes. We extended earlier works on 2D scaling relations and derived a general scaling law valid for both 2D and 3D. We then carried out two large series of numerical experiments and verified that the scaling law we have derived indeed applies to the fully non-linear case. It allowed us to extract a constraint for the rise time of magnetic flux tubes that is valid for any solar-like star. We finally introduced this constraint to a delayed dynamo model.
By carrying out simulations of a mean-field, delayed, flux tube/Babcock-Leighton dynamo, we were able to identify a new dynamo regime resulting from the delay. This regime requires delays about an entire cycle and exhibits subequipartition magnetic activity. Revealing this new regime shows that even for long delays the flux tube/Babcock-Leighton dynamo can still deliver non-decaying solutions and remains a good candidate for a wide range of solar-like stars.
Durch die Zunahme metabolischer Stoffwechselstörungen und Erkrankungen in der Weltbevölkerung wird in der Medizin und den Lebenswissenschaften vermehrt nach Präventionsstrategien und Ansatzpunkten gesucht, die die Gesundheit fördern, Erkrankungen verhindern helfen und damit auch die Gesamtlast auf die Gesundheitssysteme erleichtern. Ein Ansatzpunkt wird dabei in der Ernährung gesehen, da insbesondere der Konsum von gesättigten Fetten die Gesundheit nachträglich zu beeinflussen scheint. Dabei wird übersehen, dass in vielen Studien Hochfettdiäten nicht ausreichend von den Einflüssen einer zum Bedarf hyperkalorischen Energiezufuhr getrennt werden, sodass die Datenlage zu dem Einfluss von (gesättigten) Fetten auf den Metabolismus bei gleichbleibender Energieaufnahme noch immer unzureichend ist.
In der NUtriGenomic Analysis in Twins-Studie wurden 46 Zwillingspaare (34 monozygot, 12 dizygot) über einen Zeitraum von sechs Wochen mittels einer kohlenhydratreichen, fettarmen Diät nach Richtlinien der Deutschen Gesellschaft für Ernährung für ihr Ernährungsverhalten standardisiert, ehe sie zu einer kohlenhydratarmen, fettreichen Diät, die insbesondere gesättigte Fette enthielt, für weitere sechs Wochen wechselten. Beide Diäten waren dem individuellen Energiebedarf der Probanden angepasst, um so sowohl akut nach einerWoche als auch längerfristig nach sechs Wochen Änderungen des Metabolismus beobachten zu können, die sich in der vermehrten Aufnahme von (gesättigten) Fetten begründeten.
Die über die detaillierte Charakterisierung der Probanden an den klinischen Untersuchungstagen generierten Datensätze wurden mit statistischen und mathematischen Methoden (z.B. lineare gemischte Modellierung) analysiert, die der Größe der Datensätze und damit ihrem Informationsvolumen angepasst waren.
Es konnte gezeigt werden, dass die metabolisch gesunden und relativ jungen Probanden, die eine gute Compliance zeigten, im Hinblick auf ihren Glukosestoffwechsel adaptieren konnten, indem die Akutantwort nach einer Woche im Nüchterninsulin und dem Index für Insulinresistenz in den weiteren fünf Wochen ausgeglichen wurde.
Der Lipidstoffwechsel in Form der klassischen Marker wie Gesamtcholesterin, LDL und HDL war dagegen stärker beeinflusst und auch nach insgesamt sechs Wochen deutlich erhöht.
Letzteres unterstützt die Beobachtung im Transkriptom des weißen, subkutanen Fettgewebes, bei der eine Aktivierung der über die Toll-like receptors und das Inflammasom vermittelten subklinischen Inflammation beobachtet werden konnte.
Die auftretenden Veränderungen in Konzentration und Komposition des Plasmalipidoms zeigte ebenfalls nur eine teilweise und auf bestimmte Spezies begrenzte Gegenregulation.
Diesbezüglich kann also geschlussfolgert werden, dass auch die isokalorische Aufnahme von (gesättigten) Fetten zu Veränderungen im Metabolismus führt, wobei die Auswirkungen in weiteren (Langzeit-)Studien und Experimenten noch genauer untersucht werden müssen. Insbesondere wäre dabei ein längerer Zeitraum unter isokalorischen Bedingungen von Interesse und die Untersuchung von Probanden mit metabolischer Vorbelastung (z.B. Insulinresistenz).
Darüber hinaus konnte in NUGAT aber ebenfalls gezeigt werden, dass die Nutrigenetik und Nutrigenomik zwei nicht zu vernachlässigende Faktoren darstellen. So zeigten unter anderem die Konzentrationen einiger Lipidspezies eine starke Erblichkeit und Abhängigkeit der Diät.
Zudem legen die Ergebnisse nahe, dass laufende wie geplante Präventionsstrategien und medizinische Behandlungen deutlich stärker den Patienten als Individuum mit einbeziehen müssen, da die Datenanalyse interindividuelle Unterschiede identifizierte und Hinweise lieferte, dass einige Probanden die nachteiligen, metabolischen Auswirkungen einer Hochfettdiät besser ausgleichen konnten als andere.
Ziel der vorliegenden Arbeit ist es, belohnungsabhängiges (instrumentelles) Lernen und Entscheidungsfindungsprozesse auf Verhaltens- und neuronaler Ebene in Abhängigkeit von chronischem Stresserleben (erfasst über den Lifetime Stress Inventory, Holmes und Rahe 1962) und kognitiven Variablen (eingeteilt in eine fluide und eine kristalline Intelligenzkomponente) an gesunden Probanden zu untersuchen. Dabei steht zu Beginn die Sicherung der Konstruktvalidität zwischen den bislang oft synonym verwendeten Begriffen modellfrei ~ habituell, bzw. modellbasiert ~ zielgerichtet im Fokus. Darauf aufbauend soll dann insbesondere der differentielle und interaktionelle Einfluss von chronischem Stresserleben und kognitiven Variablen auf Entscheidungsprozesse (instrumentelles Lernen) und deren neuronales Korrelat im VS untersucht und dargestellt werden. Abschließend wird die Relevanz der untersuchten belohnungsabhängigen Lernprozesse für die Entstehung und Aufrechterhaltung der Alkoholabhängigkeit zusammen mit weiteren Einflussvariablen in einem Übersichtspapier diskutiert.
The collision of bathymetric anomalies, such as oceanic spreading centers, at convergent plate margins can profoundly affect subduction dynamics, magmatism, and the structural and geomorphic evolution of the overriding plate. The Southern Patagonian Andes of South America are a prime example for sustained oceanic ridge collision and the successive formation and widening of an extensive asthenospheric slab window since the Middle Miocene. Several of the predicted upper-plate geologic manifestations of such deep-seated geodynamic processes have been studied in this region, but many topics remain highly debated. One of the main controversial topics is the interpretation of the regional low-temperature thermochronology exhumational record and its relationship with tectonic and/or climate-driven processes, ultimately manifested and recorded in the landscape evolution of the Patagonian Andes. The prominent along-strike variance in the topographic characteristics of the Andes, combined with coupled trends in low-temperature thermochronometer cooling ages have been interpreted in very contrasting ways, considering either purely climatic (i.e. glacial erosion) or geodynamic (slab-window related) controlling factors.
This thesis focuses on two main aspects of these controversial topics. First, based on field observations and bedrock low-temperature thermochronology data, the thesis addresses an existing research gap with respect to the neotectonic activity of the upper plate in response to ridge collision - a mechanism that has been shown to affect the upper plate topography and exhumational patterns in similar tectonic settings. Secondly, the qualitative interpretation of my new and existing thermochronological data from this region is extended by inverse thermal modelling to define thermal histories recorded in the data and evaluate the relative importance of surface vs. geodynamic factors and their possible relationship with the regional cooling record.
My research is centered on the Northern Patagonian Icefield (NPI) region of the Southern Patagonian Andes. This site is located inboard of the present-day location of the Chile Triple Junction - the juncture between the colliding Chile Rise spreading center and the Nazca and Antarctic Plates along the South American convergent margin. As such this study area represents the region of most recent oceanic-ridge collision and associated slab window formation. Importantly, this location also coincides with the abrupt rise in summit elevations and relief characteristics in the Southern Patagonian Andes. Field observations, based on geological, structural and geomorphic mapping, are combined with bedrock apatite (U-Th)/He and apatite fission track (AHe and AFT) cooling ages sampled along elevation transects across the orogen. This new data reveals the existence of hitherto unrecognized neotectonic deformation along the flanks of the range capped by the NPI.
This deformation is associated with the closely spaced oblique collision of successive oceanic-ridge segments in this region over the past 6 Ma. I interpret that this has caused a crustal-scale partitioning of deformation and the decoupling, margin-parallel migration, and localized uplift of a large crustal sliver (the NPI block) along the subduction margin. The location of this uplift coincides with a major increase of summit elevations and relief at the northern edge of the NPI massif. This mechanism is compatible with possible extensional processes along the topographically subdued trailing edge of the NPI block as documented by very recent and possibly still active normal faulting. Taken together, these findings suggest a major structural control on short-wavelength variations in topography in the Southern Patagonian Andes - the region affected by ridge collision and slab window formation.
The second research topic addressed here focuses on using my new and existing bedrock low-temperature cooling ages in forward and inverse thermal modeling. The data was implemented in the HeFTy and QTQt modeling platforms to constrain the late Cenozoic thermal history of the Southern Patagonian Andes in the region of the most recent upper-plate sectors of ridge collision. The data set combines AHe and AFT data from three elevation transects in the region of the Northern Patagonian Icefield. Previous similar studies claimed far-reaching thermal effects of the approaching ridge collision and slab window to affect patterns of Late Miocene reheating in the modelled thermal histories. In contrast, my results show that the currently available data can be explained with a simpler thermal history than previously proposed. Accordingly, a reheating event is not needed to reproduce the observations. Instead, the analyzed ensemble of modelled thermal histories defines a Late Miocene protracted cooling and Pliocene-to-recent stepwise exhumation. These findings agree with the geological record of this region. Specifically, this record indicates an Early Miocene phase of active mountain building associated with surface uplift and an active fold-and-thrust belt, followed by a period of stagnating deformation, peneplanation, and lack of synorogenic deposition in the Patagonian foreland. The subsequent period of stepwise exhumation likely resulted from a combination of pulsed glacial erosion and coeval neotectonic activity. The differences between the present and previously published interpretation of the cooling record can be reconciled with important inconsistencies of previously used model setup. These include mainly the insufficient convergence of the models and improper assumptions regarding the geothermal conditions in the region. This analysis puts a methodological emphasis on the prime importance of the model setup and the need for its thorough examination to evaluate the robustness of the final outcome.
The cell interior is a highly packed environment in which biological macromolecules evolve and function. This crowded media has effects in many biological processes such as protein-protein binding, gene regulation, and protein folding. Thus, biochemical reactions that take place in such crowded conditions differ from diluted test tube conditions, and a considerable effort has been invested in order to understand such differences.
In this work, we combine different computationally tools to disentangle the effects of molecular crowding on biochemical processes. First, we propose a lattice model to study the implications of molecular crowding on enzymatic reactions. We provide a detailed picture of how crowding affects binding and unbinding events and how the separate effects of crowding on binding equilibrium act together. Then, we implement a lattice model to study the effects of molecular crowding on facilitated diffusion. We find that obstacles on the DNA impair facilitated diffusion. However, the extent of this effect depends on how dynamic obstacles are on the DNA. For the scenario in which crowders are only present in the bulk solution, we find that at some conditions presence of crowding agents can enhance specific-DNA binding. Finally, we make use of structure-based techniques to look at the impact of the presence of crowders on the folding a protein. We find that polymeric crowders have stronger effects on protein stability than spherical crowders. The strength of this effect increases as the polymeric crowders become longer. The methods we propose here are general and can also be applied to more complicated systems.
The ever-increasing fat content in Western diet, combined with decreased levels of physical activity, greatly enhance the incidence of metabolic-related diseases. Cancer cachexia (CC) and Metabolic syndrome (MetS) are both multifactorial highly complex metabolism related syndromes, whose etiology is not fully understood, as the mechanisms underlying their development are not completely unveiled. Nevertheless, despite being considered “opposite sides”, MetS and CC share several common issues such as insulin resistance and low-grade inflammation. In these scenarios, tissue macrophages act as key players, due to their capacity to produce and release inflammatory mediators. One of the main features of MetS is hyperinsulinemia, which is generally associated with an attempt of the β-cell to compensate for diminished insulin sensitivity (insulin resistance). There is growing evidence that hyperinsulinemia per se may contribute to the development of insulin resistance, through the establishment of low grade inflammation in insulin responsive tissues, especially in the liver (as insulin is secreted by the pancreas into the portal circulation). The hypothesis of the present study was that insulin may itself provoke an inflammatory response culminating in diminished hepatic insulin sensitivity. To address this premise, firstly, human cell line U937 differentiated macrophages were exposed to insulin, LPS and PGE2. In these cells, insulin significantly augmented the gene expression of the pro-inflammatory mediators IL-1β, IL-8, CCL2, Oncostatin M (OSM) and microsomal prostaglandin E2 synthase (mPGES1), and of the anti-inflammatory mediator IL-10. Moreover, the synergism between insulin and LPS enhanced the induction provoked by LPS in IL-1β, IL-8, IL-6, CCL2 and TNF-α gene. When combined with PGE2, insulin enhanced the induction provoked by PGE2 in IL-1β, mPGES1 and COX2, and attenuated the inhibition induced by PGE2 in CCL2 and TNF-α gene expression contributing to an enhanced inflammatory response by both mechanisms. Supernatants of insulin-treated U937 macrophages reduced the insulin-dependent induction of glucokinase in hepatocytes by 50%. Cytokines contained in the supernatant of insulin-treated U937 macrophages also activated hepatocytes ERK1/2, resulting in inhibitory serine phosphorylation of the insulin receptor substrate. Additionally, the transcription factor STAT3 was activated by phosphorylation resulting in the induction of SOCS3, which is capable of interrupting the insulin receptor signal chain. MicroRNAs, non-coding RNAs linked to protein expression regulation, nowadays recognized as active players in the generation of several inflammatory disorders such as cancer and type II diabetes are also of interest. Considering that in cancer cachexia, patients are highly affected by insulin resistance and inflammation, control, non-cachectic and cachectic cancer patients were selected and the respective circulating levels of pro-inflammatory mediators and microRNA-21-5p, a posttranscriptional regulator of STAT3 expression, assessed and correlated. Cachectic patients circulating cytokines IL-6 and IL-8 levels were significantly higher than those of non-cachectic and controls, and the expression of microRNA-21-5p was significantly lower. Additionally, microRNA-21-5p reduced expression correlated negatively with IL-6 plasma levels. These results indicate that hyperinsulinemia per se might contribute to the low grade inflammation prevailing in MetS patients and thereby promote the development
of insulin resistance particularly in the liver. Diminished MicroRNA-21-5p expression may enhance inflammation and STAT3 expression in cachectic patients, contributing to the development of insulin resistance.
The human immunodeficiency virus (HIV) has resisted nearly three decades of efforts targeting a cure. Sustained suppression of the virus has remained a challenge, mainly due
to the remarkable evolutionary adaptation that the virus exhibits by the accumulation of drug-resistant mutations in its genome. Current therapeutic strategies aim at achieving and maintaining a low viral burden and typically involve multiple drugs. The choice of optimal combinations of these drugs is crucial, particularly in the background of treatment failure having occurred previously with certain other drugs. An understanding of the dynamics of viral mutant genotypes aids in the assessment of treatment failure with a certain drug
combination, and exploring potential salvage treatment regimens.
Mathematical models of viral dynamics have proved invaluable in understanding the viral life cycle and the impact of antiretroviral drugs. However, such models typically use simplified and coarse-grained mutation schemes, that curbs the extent of their application to drug-specific clinical mutation data, in order to assess potential next-line therapies. Statistical
models of mutation accumulation have served well in dissecting mechanisms of resistance evolution by reconstructing mutation pathways under different drug-environments. While these models perform well in predicting treatment outcomes by statistical learning, they do not incorporate drug effect mechanistically. Additionally, due to an inherent lack of
temporal features in such models, they are less informative on aspects such as predicting mutational abundance at treatment failure. This limits their application in analyzing the
pharmacology of antiretroviral drugs, in particular, time-dependent characteristics of HIV therapy such as pharmacokinetics and pharmacodynamics, and also in understanding the impact of drug efficacy on mutation dynamics.
In this thesis, we develop an integrated model of in vivo viral dynamics incorporating drug-specific mutation schemes learned from clinical data. Our combined modelling
approach enables us to study the dynamics of different mutant genotypes and assess mutational abundance at virological failure. As an application of our model, we estimate in vivo
fitness characteristics of viral mutants under different drug environments. Our approach also extends naturally to multiple-drug therapies. Further, we demonstrate the versatility of our model by showing how it can be modified to incorporate recently elucidated mechanisms of drug action including molecules that target host factors.
Additionally, we address another important aspect in the clinical management of HIV disease, namely drug pharmacokinetics. It is clear that time-dependent changes in in vivo
drug concentration could have an impact on the antiviral effect, and also influence decisions on dosing intervals. We present a framework that provides an integrated understanding
of key characteristics of multiple-dosing regimens including drug accumulation ratios and half-lifes, and then explore the impact of drug pharmacokinetics on viral suppression.
Finally, parameter identifiability in such nonlinear models of viral dynamics is always a concern, and we investigate techniques that alleviate this issue in our setting.
The lakes in the Kenyan Rift Valley offer the unique opportunity to study a wide range of hydrochemical environmental conditions, ranging from freshwater to highly saline and alkaline lakes. Because little is known about the hydro- and biogeochemical conditions in the underlying lake sediments, it was the aim of this study to extend the already existing data sets with data from porewater and biomarker analyses. Additionally, reduced sulphur compounds and sulphate reduction rates in the sediment were determined. The new data was used to examine the anthropogenic and microbial influence on the lakes sediments as well as the influence of the water chemistry on the degradation and preservation of organic matter in the sediment column. The lakes discussed in this study are: Logipi, Eight (a small crater lake in the region of Kangirinyang), Baringo, Bogoria, Naivasha, Oloiden, and Sonachi.
The biomarker compositions were similar in all studied lake sediments; nevertheless, there were some differences between the saline and freshwater lakes. One of those differences is the occurrence of a molecule related to β-carotene, which was only found in the saline lakes. This molecule most likely originates from cyanobacteria, single-celled organisms which are commonly found in saline lakes. In the two freshwater lakes, stigmasterol, a sterol characteristic for freshwater algae, was found. In this study, it was shown that Lakes Bogoria and Sonachi can be used for environmental reconstructions with biomarkers, because the absence of oxygen at the lake bottoms slowed the degradation process. Other lakes, like for example Lake Naivasha, cannot be used for such reconstructions, because of the large anthropogenic influence. But the biomarkers proved to be a useful tool to study those anthropogenic influences. Additionally, it was observed that horizons with a high concentration of elemental sulphur can be used as temporal markers. Those horizons were deposited during times when the lake levels were very low. The sulphur was deposited by microorganisms which are capable of anoxygenic photosynthesis or sulphide oxidation.
The relationship between climate and forest productivity is an intensively studied subject in forest science. This Thesis is embedded within the general framework of future forest growth under climate change and its implications for the ongoing forest conversion. My objective is to investigate the future forest productivity at different spatial scales (from a single specific forest stand to aggregated information across Germany) with focus on oak-pine forests in the federal state of Brandenburg. The overarching question is: how are the oak-pine forests affected by climate change described by a variety of climate scenarios. I answer this question by using a model based analysis of tree growth processes and responses to different climate scenarios with emphasis on drought events. In addition, a method is developed which considers climate change uncertainty of forest management planning.
As a first 'screening' of climate change impacts on forest productivity, I calculated the change in net primary production on the base of a large set of climate scenarios for different tree species and the total area of Germany. Temperature increases up to 3 K lead to positive effects on the net primary production of all selected tree species. But, in water-limited regions this positive net primary production trend is dependent on the length of drought periods which results in a larger uncertainty regarding future forest productivity. One of the regions with the highest uncertainty of net primary production development is the federal state of Brandenburg.
To enhance the understanding and ability of model based analysis of tree growth sensitivity to drought stress two water uptake approaches in pure pine and mixed oak-pine stands are contrasted. The first water uptake approach consists of an empirical function for root water uptake. The second approach is more mechanistic and calculates the differences of soil water potential along a soil-plant-atmosphere continuum. I assumed the total root resistance to vary at low, medium and high total root resistance levels. For validation purposes three data sets on different tree growth relevant time scales are used. Results show that, except the mechanistic water uptake approach with high total root resistance, all transpiration outputs exceeded observed values. On the other hand high transpiration led to a better match of observed soil water content. The strongest correlation between simulated and observed annual tree ring width occurred with the mechanistic water uptake approach and high total root resistance. The findings highlight the importance of severe drought as a main reason for small diameter increment, best supported by the mechanistic water uptake approach with high root resistance. However, if all aspects of the data sets are considered no approach can be judged superior to the other. I conclude that the uncertainty of future productivity of water-limited forest ecosystems under changing environmental conditions is linked to simulated root water uptake.
Finally my study aimed at the impacts of climate change combined with management scenarios on an oak-pine forest to evaluate growth, biomass and the amount of harvested timber. The pine and the oak trees are 104 and 9 years old respectively. Three different management scenarios with different thinning intensities and different climate scenarios are used to simulate the performance of management strategies which explicitly account for the risks associated with achieving three predefined objectives (maximum carbon storage, maximum harvested timber, intermediate). I found out that in most cases there is no general management strategy which fits best to different objectives. The analysis of variance in the growth related model outputs showed an increase of climate uncertainty with increasing climate warming. Interestingly, the increase of climate-induced uncertainty is much higher from 2 to 3 K than from 0 to 2 K.
Difficulties with object relative clauses (ORC), as compared to subject relative clauses (SR), are widely attested across different languages, both in adults and in children. This SR-ORC asymmetry is reduced, or even eliminated, when the embedded constituent in the ORC is a pronoun, rather than a lexical noun phrase. The studies included in this thesis were designed to explore under what circumstances the pronoun facilitation occurs; whether all pronouns have the same effect; whether SRs are also affected by embedded pronouns; whether children perform like adults on such structures; and whether performance is related to cognitive abilities such as memory or grammatical knowledge. Several theoretical approaches that explain the pronoun facilitation in relative clauses are evaluated. The experimental data have been collected in three languages–German, Italian and Hebrew–stemming from both children and adults.
In the German study (Chapter 2), ORCs with embedded 1st- or 3rd-person pronouns are compared to ORCs with an embedded lexical noun phrase. Eye-movement data from 5-year-old children show that the 1st-person pronoun facilitates processing, but not the 3rd-person pronoun. Moreover, children’s performance is modulated by additive effects of their memory and grammatical skills. In the Italian study (Chapter 3), the 1st-person pronoun advantage over the 3rd-person pronoun is tested in ORCs and SRs that display a similar word order. Eye-movement data from 5-year-olds and adult controls and reading times data from adults are pitted against the outcome of a corpus analysis, showing that the 1st-/3rd-person pronoun asymmetry emerges in the two relative clause types to an equal extent. In the Hebrew study (Chapter 4), the goal is to test the effect of a special kind of pronoun–a non-referential arbitrary subject pronoun–on ORC comprehension, in the light of potential confounds in previous studies that used this pronoun. Data from a referent-identification task with 4- to 5-year-olds indicate that, when the experimental material is controlled, the non-referential pronoun does not necessarily facilitate ORC comprehension. Importantly, however, children have even more difficulties when the embedded constituent is a referential pronoun. The non-referentiality / referentiality asymmetry is emphasized by the relation between children’s performance on the experimental task and their memory skills.
Together, the data presented in this thesis indicate that sentence processing is not only driven by structural (or syntactic) factors, but also by discourse-related ones, like pronouns’ referential properties or their discourse accessibility mechanism, which is defined as the level of ease or difficulty with which referents of pronouns are identified and retrieved from the discourse model. Although independent in essence, these structural and discourse factors can in some cases interact in a way that affects sentence processing. Moreover, both types of factors appear to be strongly related to memory. The data also support the idea that, from early on, children are sensitive to the same factors that affect adults’ sentence processing, and that the processing strategies of both populations are qualitatively similar.
In sum, this thesis suggests that a comprehensive theory of human sentence processing needs to account for effects that are due to both structural and discourse-related factors, which operate as a function of memory capacity.
Möglichkeiten der Mittelstandsförderung durch Vergaberechtsgestaltung und Vergaberechtspraxis
(2016)
Die Förderungswürdigkeit und die Förderungsfähigkeit mittelständischer Unternehmen ist ein gesamteuropäisches, wirtschaftspolitisches Anliegen. Hiervon zeugen zum einen zahlreiche Regelungen im Primär-, Sekundär-, Verfassungs- und einfachgesetzlichem Recht, zum anderen auch die Bedeutung der mittelständischen Unternehmen im wirtschaftlichen, gesellschaftlichen und sozialen Gefüge. So herrscht innerhalb der Europäischen Union nicht nur der Slogan „Vorfahrt für KMU“, sondern auch die im Frühjahr 2014 verabschiedeten Vergaberichtlinien legten ein besonderes Augenmerk auf die Förderung des Zugangs der KMU zum öffentlichen Beschaffungsmarkt. Denn gemessen am Steuerungs- und Lenkungspotenzial der Auftragsvergabe, deren Einfluss auf die Innovationstätigkeit der Wirtschaft sowie deren Auswirkungen auf die Wirtschafts- und Wettbewerbstätigkeit auf der einen Seite und dem gesamtwirtschaftlichen Stellenwert der mittelständischen Unternehmen auf der anderen Seite, sind mittelständische Unternehmen trotz zahlreicher europäischer und nationaler Initiativen im Vergabeverfahren unterrepräsentiert. Neben der undurchsichtigen Regelungsstruktur des deutschen Vergaberechts, unterliegen die mittelständischen Unternehmen vom Beginn bis zum Ende des Vergabeverfahrens besonderen Schwierigkeiten. Dieser Ausgangsbefund wurde zum Anlass genommen, um die Möglichkeiten der Mittelstandsförderung durch Vergaberechtsgestaltung und Vergaberechtspraxis erneut auf den Prüfstand zu stellen.
In recent years, entire industries and their participants have been affected by disruptive technologies, resulting in dramatic market changes and challenges to firm’s business logic and thus their business models (BMs). Firms from mature industries are increasingly realizing that BMs that worked successfully for years have become insufficient to stay on track in today’s “move fast and break things” economy. Firms must scrutinize the core logic that informs how they do business, which means exploring novel ways to engage customers and get them to pay. This can lead to a complete renewal of existing BMs or innovating completely new BMs.
BMs have emerged as a popular object of research within the last decade. Despite the popularity of the BM, the theoretical and empirical foundation underlying the concept is still weak. In particular, the innovation process for BMs has been developed and implemented in firms, but understanding of the mechanisms behind it is still lacking. Business model innovation (BMI) is a complex and challenging management task that requires more than just novel ideas. Systematic studies to generate a better understanding of BMI and support incumbents with appropriate concepts to improve BMI development are in short supply. Further, there is a lack of knowledge about appropriate research practices for studying BMI and generating valid data sets in order to meet expectations in both practice and academia.
This paper-based dissertation aims to contribute to research practice in the field of BM and BMI and foster better understanding of the BM concept and BMI processes in incumbent firms from mature industries. The overall dissertation presents three main results. The first result is a new perspective, or the systems thinking view, on the BM and BMI. With the systems thinking view, the fuzzy BM concept is clearly structured and a BMI framework is proposed. The second result is a new research strategy for studying BMI. After analyzing current research practice in the areas of BMs and BMI, it is obvious that there is a need for better research on BMs and BMI in terms of accuracy, transparency, and practical orientation. Thus, the action case study approach combined with abductive methodology is proposed and proven in the research setting of this thesis. The third result stems from three action case studies in incumbent firms from mature industries employed to study how BMI occurs in practice. The new insights and knowledge gained from the action case studies help to explain BMI in such industries and increase understanding of the core of these processes.
By studying these issues, the articles complied in this thesis contribute conceptually and empirically to the recently consolidated but still increasing literature on the BM and BMI. The conclusions and implications made are intended to foster further research and improve managerial practices for achieving BMI in a dramatically changing business environment.