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In the last decade, the number and dimensions of catastrophic flooding events in the Niger River Basin (NRB) have markedly increased. Despite the devastating impact of the floods on the population and the mainly agriculturally based economy of the riverine nations, awareness of the hazards in policy and science is still low. The urgency of this topic and the existing research deficits are the motivation for the present dissertation.
The thesis is an initial detailed assessment of the increasing flood risk in the NRB. The research strategy is based on four questions regarding (1) features of the change in flood risk, (2) reasons for the change in the flood regime, (3) expected changes of the flood regime given climate and land use changes, and (4) recommendations from previous analysis for reducing the flood risk in the NRB.
The question examining the features of change in the flood regime is answered by means of statistical analysis. Trend, correlation, changepoint, and variance analyses show that, in addition to the factors exposure and vulnerability, the hazard itself has also increased significantly in the NRB, in accordance with the decadal climate pattern of West Africa. The northern arid and semi-arid parts of the NRB are those most affected by the changes.
As potential reasons for the increase in flood magnitudes, climate and land use changes are attributed by means of a hypothesis-testing framework. Two different approaches, based on either data analysis or simulation, lead to similar results, showing that the influence of climatic changes is generally larger compared to that of land use changes. Only in the dry areas of the NRB is the influence of land use changes comparable to that of climatic alterations.
Future changes of the flood regime are evaluated using modelling results. First ensembles of statistically and dynamically downscaled climate models based on different emission scenarios are analyzed. The models agree with a distinct increase in temperature. The precipitation signal, however, is not coherent. The climate scenarios are used to drive an eco-hydrological model. The influence of climatic changes on the flood regime is uncertain due to the unclear precipitation signal. Still, in general, higher flood peaks are expected. In a next step, effects of land use changes are integrated into the model. Different scenarios show that regreening might help to reduce flood peaks. In contrast, an expansion of agriculture might enhance the flood peaks in the NRB. Similarly to the analysis of observed changes in the flood regime, the impacts of climate- and land use changes for the future scenarios are also most severe in the dry areas of the NRB.
In order to answer the final research question, the results of the above analysis are integrated into a range of recommendations for science and policy on how to reduce flood risk in the NRB. The main recommendations include a stronger consideration of the enormous natural climate variability in the NRB and a focus on so called “no-regret” adaptation strategies which account for high uncertainty, as well as a stronger consideration of regional differences. Regarding the prevention and mitigation of catastrophic flooding, the most vulnerable and sensitive areas in the basin, the arid and semi-arid Sahelian and Sudano-Sahelian regions, should be prioritized. Eventually, an active, science-based and science-guided flood policy is recommended. The enormous population growth in the NRB in connection with the expected deterioration of environmental and climatic conditions is likely to enhance the region´s vulnerability to flooding. A smart and sustainable flood policy can help mitigate these negative impacts of flooding on the development of riverine societies in West Africa.
The Central Pontides is an accretionary-type orogenic area within the Alpine-Himalayan orogenic belt characterized by pre-collisional tectonic continental growth. The region comprises Mesozoic subduction-accretionary complexes and an accreted intra-oceanic arc that are sandwiched between the Laurasian active continental margin and Gondwana-derived the Kırşehir Block. The subduction-accretion complexes mainly consist of an Albian-Turonian accretionary wedge representing the Laurasian active continental margin. To the north, the wedge consists of slate/phyllite and metasandstone intercalation with recrystallized limestone, Na-amphibole-bearing metabasite (PT= 7–12 kbar and 400 ± 70 ºC) and tectonic slices of serpentinite representing accreted distal part of a large Lower Cretaceous submarine turbidite fan deposited on the Laurasian active continental margin that was subsequently accreted and metamorphosed. Raman spectra of carbonaceous material (RSCM) of the metapelitic rocks revealed that the metaflysch sequence consists of metamorphic packets with distinct peak metamorphic temperatures. The majority of the metapelites are low-temperature (ca. 330 °C) slates characterized by lack of differentiation of the graphite (G) and D2 defect bands. They possibly represent offscraped distal turbidites along the toe of the Albian accretionary wedge. The rest are phyllites that are characterized by slightly pronounced G band with D2 defect band occurring on its shoulder. Peak metamorphic temperatures of these phyllites are constrained to 370-385 °C. The phyllites are associated with a strip of incipient blueschist facies metabasites which are found as slivers within the offscraped distal turbidites. They possibly represent underplated continental metasediments together with oceanic crustal basalt along the basal décollement. Tectonic emplacement of the underplated rocks into the offscraped distal turbidites was possibly achieved by out-of-sequence thrusting causing tectonic thickening and uplift of the wedge. 40Ar/39Ar phengite ages from the phyllites are ca. 100 Ma, indicating Albian subduction and regional HP metamorphism.
The accreted continental metasediments are underlain by HP/LT metamorphic rocks of oceanic origin along an extensional shear zone. The oceanic metamorphic sequence mainly comprises tectonically thickened deep-seated eclogite to blueschist facies metabasites and micaschists. In the studied area, metabasites are epidote-blueschists locally with garnet (PT= 17 ± 1 kbar and 500 ± 40 °C). Lawsonite-blueschists are exposed as blocks along the extensional shear zone (PT= 14 ± 2 kbar and 370–440 °C). They are possibly associated with low shear stress regime of the initial stage of convergence. Close to the shear zone, the footwall micaschists consist of quartz, phengite, paragonite, chlorite, rutile with syn-kinematic albite porphyroblast formed by pervasive shearing during exhumation. These types of micaschists are tourmaline-bearing and their retrograde nature suggests high-fluid flux along shear zones. Peak metamorphic mineral assemblages are partly preserved in the chloritoid-micaschist farther away from the shear zone representing the zero strain domains during exhumation. Three peak metamorphic assemblages are identified and their PT conditions are constrained by pseudosections produced by Theriak-Domino and by Raman spectra of carbonaceous material: 1) garnet-chloritoid-glaucophane with lawsonite pseudomorphs (P= 17.5 ± 1 kbar, T: 390-450 °C) 2) chloritoid with glaucophane pseudomorphs (P= 16-18 kbar, T: 475 ± 40 °C) and 3) relatively high-Mg chloritoid (17%) with jadeite pseudomorphs (P= 22-25 kbar; T: 440 ± 30 °C) in addition to phengite, paragonite, quartz, chlorite, rutile and apatite. The last mineral assemblage is interpreted as transformation of the chloritoid + glaucophane assemblage to chloritoid + jadeite paragenesis with increasing pressure. Absence of tourmaline suggests that the chloritoid-micaschist did not interact with B-rich fluids during zero strain exhumation. 40Ar/39Ar phengite age of a pervasively sheared footwall micaschist is constrained to 100.6 ± 1.3 Ma and that of a chloritoid-micaschist is constrained to 91.8 ± 1.8 Ma suggesting exhumation during on-going subduction with a southward younging of the basal accretion and the regional metamorphism. To the south, accretionary wedge consists of blueschist and greenschist facies metabasite, marble and volcanogenic metasediment intercalation. 40Ar/39Ar phengite dating reveals that this part of the wedge is of Middle Jurassic age partly overprinted during the Albian. Emplacement of the Middle Jurassic subduction-accretion complexes is possibly associated with obliquity of the Albian convergence.
Peak metamorphic assemblages and PT estimates of the deep-seated oceanic metamorphic sequence suggest tectonic stacking within wedge with different depths of burial. Coupling and exhumation of the distinct metamorphic slices are controlled by decompression of the wedge possibly along a retreating slab. Structurally, decompression of the wedge is evident by an extensional shear zone and the footwall micaschists with syn-kinematic albite porphyroblasts. Post-kinematic garnets with increasing grossular content and pseudomorphing minerals within the chloritoid-micaschists also support decompression model without an extra heating.
Thickening of subduction-accretionary complexes is attributed to i) significant amount of clastic sediment supply from the overriding continental domain and ii) deep level basal underplating by propagation of the décollement along a retreating slab. Underplating by basal décollement propagation and subsequent exhumation of the deep-seated subduction-accretion complexes are connected and controlled by slab rollback creating a necessary space for progressive basal accretion along the plate interface and extension of the wedge above for exhumation of the tectonically thickened metamorphic sequences. This might be the most common mechanism of the tectonic thickening and subsequent exhumation of deep-seated HP/LT subduction-accretion complexes.
To the south, the Albian-Turonian accretionary wedge structurally overlies a low-grade volcanic arc sequence consisting of low-grade metavolcanic rocks and overlying metasedimentary succession is exposed north of the İzmir-Ankara-Erzincan suture (İAES), separating Laurasia from Gondwana-derived terranes. The metavolcanic rocks mainly consist of basaltic andesite/andesite and mafic cognate xenolith-bearing rhyolite with their pyroclastic equivalents, which are interbedded with recrystallized pelagic limestone and chert. The metavolcanic rocks are stratigraphically overlain by recrystallized micritic limestone with rare volcanogenic metaclastic rocks. Two groups can be identified based on trace and rare earth element characteristics. The first group consists of basaltic andesite/andesite (BA1) and rhyolite with abundant cognate gabbroic xenoliths. It is characterized by relative enrichment of LREE with respect to HREE. The rocks are enriched in fluid mobile LILE, and strongly depleted in Ti and P reflecting fractionation of Fe-Ti oxides and apatite, which are found in the mafic cognate xenoliths. Abundant cognate gabbroic xenoliths and identical trace and rare earth elements compositions suggest that rhyolites and basaltic andesites/andesites (BA1) are cogenetic and felsic rocks were derived from a common mafic parental magma by fractional crystallization and accumulation processes. The second group consists only of basaltic andesites (BA2) with flat REE pattern resembling island arc tholeiites. Although enriched in LILE, this group is not depleted in Ti or P.
Geochemistry of the metavolcanic rocks indicates supra-subduction volcanism evidenced by depletion of HFSE and enrichment of LILE. The arc sequence is sandwiched between an Albian-Turonian subduction-accretionary complex representing the Laurasian active margin and an ophiolitic mélange. Absence of continent derived detritus in the arc sequence and its tectonic setting in a wide Cretaceous accretionary complex suggest that the Kösdağ Arc was intra-oceanic. This is in accordance with basaltic andesites (BA2) with island arc tholeiite REE pattern.
Zircons from two metarhyolite samples give Late Cretaceous (93.8 ± 1.9 and 94.4 ± 1.9 Ma) U/Pb ages. Low-grade regional metamorphism of the intra-oceanic arc sequence is constrained 69.9 ± 0.4 Ma by 40Ar/39Ar dating on metamorphic muscovite from a metarhyolite indicating that the arc sequence became part of a wide Tethyan Cretaceous accretionary complex by the latest Cretaceous. The youngest 40Ar/39Ar phengite age from the overlying subduction-accretion complexes is 92 Ma confirming southward younging of an accretionary-type orogenic belt. Hence, the arc sequence represents an intra-oceanic paleo-arc that formed above the sinking Tethyan slab and finally accreted to Laurasian active continental margin. Abrupt non-collisional termination of arc volcanism was possibly associated with southward migration of the arc volcanism similar to the Izu-Bonin-Mariana arc system.
The intra-oceanic Kösdağ Arc is coeval with the obducted supra-subduction ophiolites in NW Turkey suggesting that it represents part of the presumed but missing incipient intra-oceanic arc associated with the generation of the regional supra-subduction ophiolites. Remnants of a Late Cretaceous intra-oceanic paleo-arc and supra-subduction ophiolites can be traced eastward within the Alp-Himalayan orogenic belt. This reveals that Late Cretaceous intra-oceanic subduction occurred as connected event above the sinking Tethyan slab. It resulted as arc accretion to Laurasian active margin and supra-subduction ophiolite obduction on Gondwana-derived terranes.
Nowadays, business processes are increasingly supported by IT services that produce massive amounts of event data during process execution. Aiming at a better process understanding and improvement, this event data can be used to analyze processes using process mining techniques. Process models can be automatically discovered and the execution can be checked for conformance to specified behavior. Moreover, existing process models can be enhanced and annotated with valuable information, for example for performance analysis. While the maturity of process mining algorithms is increasing and more tools are entering the market, process mining projects still face the problem of different levels of abstraction when comparing events with modeled business activities. Mapping the recorded events to activities of a given process model is essential for conformance checking, annotation and understanding of process discovery results. Current approaches try to abstract from events in an automated way that does not capture the required domain knowledge to fit business activities. Such techniques can be a good way to quickly reduce complexity in process discovery. Yet, they fail to enable techniques like conformance checking or model annotation, and potentially create misleading process discovery results by not using the known business terminology.
In this thesis, we develop approaches that abstract an event log to the same level that is needed by the business. Typically, this abstraction level is defined by a given process model. Thus, the goal of this thesis is to match events from an event log to activities in a given process model. To accomplish this goal, behavioral and linguistic aspects of process models and event logs as well as domain knowledge captured in existing process documentation are taken into account to build semiautomatic matching approaches. The approaches establish a pre--processing for every available process mining technique that produces or annotates a process model, thereby reducing the manual effort for process analysts. While each of the presented approaches can be used in isolation, we also introduce a general framework for the integration of different matching approaches.
The approaches have been evaluated in case studies with industry and using a large industry process model collection and simulated event logs. The evaluation demonstrates the effectiveness and efficiency of the approaches and their robustness towards nonconforming execution logs.
Microsaccades
(2015)
The first thing we do upon waking is open our eyes. Rotating them in our eye sockets, we scan our surroundings and collect the information into a picture in our head. Eye movements can be split into saccades and fixational eye movements, which occur when we attempt to fixate our gaze. The latter consists of microsaccades, drift and tremor. Before we even lift our eye lids, eye movements – such as saccades and microsaccades that let the eyes jump from one to another position – have partially been prepared in the brain stem. Saccades and microsaccades are often assumed to be generated by the same mechanisms. But how saccades and microsaccades can be classified according to shape has not yet been reported in a statistical manner. Research has put more effort into the investigations of microsaccades’ properties and generation only since the last decade. Consequently, we are only beginning to understand the dynamic processes governing microsaccadic eye movements. Within this thesis, the dynamics governing the generation of microsaccades is assessed and the development of a model for the underlying processes. Eye movement trajectories from different experiments are used, recorded with a video-based eye tracking technique, and a novel method is proposed for the scale-invariant detection of saccades (events of large amplitude) and microsaccades (events of small amplitude). Using a time-frequency approach, the method is examined with different experiments and validated against simulated data. A shape model is suggested that allows for a simple estimation of saccade- and microsaccade related properties. For sequences of microsaccades, in this thesis a time-dynamic Markov model is proposed, with a memory horizon that changes over time and which can best describe sequences of microsaccades.
Semi-empirical sea-level models (SEMs) exploit physically motivated empirical relationships between global sea level and certain drivers, in the following global mean temperature. This model class evolved as a supplement to process-based models (Rahmstorf (2007)) which were unable to fully represent all relevant processes. They thus failed to capture past sea-level change (Rahmstorf et al. (2012)) and were thought likely to underestimate future sea-level rise. Semi-empirical models were found to be a fast and useful tool for exploring the uncertainties in future sea-level rise, consistently giving significantly higher projections than process-based models.
In the following different aspects of semi-empirical sea-level modelling have been studied. Models were first validated using various data sets of global sea level and temperature. SEMs were then used on the glacier contribution to sea level, and to infer past global temperature from sea-level data via inverse modelling. Periods studied encompass the instrumental period, covered by tide gauges (starting 1700 CE (Common Era) in Amsterdam) and satellites (first launched in 1992 CE), the era from 1000 BCE (before CE) to present, and the full length of the Holocene (using proxy data). Accordingly different data, model formulations and implementations have been used. It could be shown in Bittermann et al. (2013) that SEMs correctly predict 20th century sea-level when calibrated with data until 1900 CE. SEMs also turned out to give better predictions than the Intergovernmental Panel on Climate Change (IPCC) 4th assessment report (AR4, IPCC (2007)) models, for the period from 1961–2003 CE.
With the first multi-proxy reconstruction of global sea-level as input, estimate of the human-induced component of modern sea-level change and projections of future sea-level rise were calculated (Kopp et al. (2016)). It turned out with 90% confidence that more than 40 % of the observed 20th century sea-level rise is indeed anthropogenic. With the new semi-empirical and IPCC (2013) 5th assessment report (AR5) projections the gap between SEM and process-based model projections closes, giving higher credibility to both. Combining all scenarios, from strong mitigation to business as usual, a global sea-level rise of 28–131 cm relative to 2000 CE, is projected with 90% confidence. The decision for a low carbon pathway could halve the expected global sea-level rise by 2100 CE.
Present day temperature and thus sea level are driven by the globally acting greenhouse-gas forcing. Unlike that, the Milankovich forcing, acting on Holocene timescales, results mainly in a northern-hemisphere temperature change. Therefore a semi-empirical model can be driven with northernhemisphere temperatures, which makes it possible to model the main subcomponent of sea-level change over this period. It showed that an additional positive constant rate of the order of the estimated Antarctic sea-level contribution is then required to explain the sea-level evolution over the Holocene. Thus the global sea level, following the climatic optimum, can be interpreted as the sum of a temperature induced sea-level drop and a positive long-term contribution, likely an ongoing response to deglaciation coming from Antarctica.
Zellbasierte heterologe Expressionssysteme bieten ein einfaches und schnelles Verfahren, um neue Süßstoffe oder Süßverstärker zu finden. Unter Verwendung eines solchen Testsystems, konnte ich in Zusammenarbeit mit der Symrise AG, Holzminden und dem Institut für Pflanzenbiochemie in Halle/Saale die vietnamesische Pflanze Mycetia balansae als Quelle eines neuen Süßstoffs identifizieren. Deren Hauptkomponenten, genannt Balansine, aktivieren spezifisch den humanen Süßrezeptor. Chimäre Rezeptoren zeigten, dass die amino-terminalen Domänen der Süßrezeptoruntereinheiten, welche ein Großteil der Liganden des Süßrezeptors binden, für dessen Aktivierung durch Balansin A nicht notwendig sind.
Voraussetzung für die Anwendung zellbasierter Testsysteme zum Auffinden neuer Süßstoffe ist jedoch, dass süße Substanzen gesichert identifiziert werden, während nicht süße Substanzen zuverlässig keine Rezeptoraktivierung aufweisen. Während in HEK293 TAS1R2 TAS1R3To Galpha15i3-Zellen Süßrezeptoraktivierung gegenüber nicht süß schmeckenden Substanzen beobachtet wurde, konnte mit den HEK293PEAKrapid Galpha15-Zellen ein zuverlässiges Testsystem identifiziert, welches den Süßgeschmack der untersuchten Substanzen widerspiegelte.
Es fanden sich keine Hinweise, dass akzessorische Proteine oder verwandte Rezeptoren des Süßrezeptors das unterschiedliche Verhalten der Zellen verursachen. Es konnte gezeigt werden, dass die Verwendung unterschiedlicher G-Proteine die Signalamplituden des Süßrezeptors beeinflusst, die Unterschiede zwischen den Zellsystemen jedoch nicht vollständig erklärt. Keine der untersuchten Galpha-Proteinchimären spiegelte die intrinsische Süße der Substanzen wider.
Wenn auch nicht ursächlich für die Diskrepanz zwischen Süßrezeptoraktivierung in vitro und Süßgeschmack in vivo, so weisen die Ergebnisse dieser Arbeit auf eine Interaktion der Süßrezeptoruntereinheiten mit dem humanen Calcium-sensing Rezeptor hin. Vanillin und Ethylvanillin konnten als neue Agonisten des Calcium-sensing Rezeptors identifiziert werden.
Wie die vorliegende Arbeit zeigt, können sich kleine Unterschiede im Zellhintergrund deutlich auf die Funktionsweise heterolog exprimierter Rezeptoren auswirken. Dies zeigt wie wichtig die Wahl der Zellen für solche Screeningsysteme ist.
Adjustment of empirically derived ground motion prediction equations (GMPEs), from a data- rich region/site where they have been derived to a data-poor region/site, is one of the major challenges associated with the current practice of seismic hazard analysis. Due to the fre- quent use in engineering design practices the GMPEs are often derived for response spectral ordinates (e.g., spectral acceleration) of a single degree of freedom (SDOF) oscillator. The functional forms of such GMPEs are based upon the concepts borrowed from the Fourier spectral representation of ground motion. This assumption regarding the validity of Fourier spectral concepts in the response spectral domain can lead to consequences which cannot be explained physically.
In this thesis, firstly results from an investigation that explores the relationship between Fourier and response spectra, and implications of this relationship on the adjustment issues of GMPEs, are presented. The relationship between the Fourier and response spectra is explored by using random vibration theory (RVT), a framework that has been extensively used in earthquake engineering, for instance within the stochastic simulation framework and in the site response analysis. For a 5% damped SDOF oscillator the RVT perspective of response spectra reveals that no one-to-one correspondence exists between Fourier and response spectral ordinates except in a limited range (i.e., below the peak of the response spectra) of oscillator frequencies. The high oscillator frequency response spectral ordinates are dominated by the contributions from the Fourier spectral ordinates that correspond to the frequencies well below a selected oscillator frequency. The peak ground acceleration (PGA) is found to be related with the integral over the entire Fourier spectrum of ground motion which is in contrast to the popularly held perception that PGA is a high-frequency phenomenon of ground motion.
This thesis presents a new perspective for developing a response spectral GMPE that takes the relationship between Fourier and response spectra into account. Essentially, this frame- work involves a two-step method for deriving a response spectral GMPE: in the first step two empirical models for the FAS and for a predetermined estimate of duration of ground motion are derived, in the next step, predictions from the two models are combined within the same RVT framework to obtain the response spectral ordinates. In addition to that, a stochastic model based scheme for extrapolating the individual acceleration spectra beyond the useable frequency limits is also presented. To that end, recorded acceleration traces were inverted to obtain the stochastic model parameters that allow making consistent extrapola- tion in individual (acceleration) Fourier spectra. Moreover an empirical model, for a dura- tion measure that is consistent within the RVT framework, is derived. As a next step, an oscillator-frequency-dependent empirical duration model is derived that allows obtaining the most reliable estimates of response spectral ordinates. The framework of deriving the response spectral GMPE presented herein becomes a self-adjusting model with the inclusion of stress parameter (∆σ) and kappa (κ0) as the predictor variables in the two empirical models. The entire analysis of developing the response spectral GMPE is performed on recently compiled RESORCE-2012 database that contains recordings made from Europe, the Mediterranean and the Middle East. The presented GMPE for response spectral ordinates should be considered valid in the magnitude range of 4 ≤ MW ≤ 7.6 at distances ≤ 200 km.
Der Na⁺-K⁺-2Cl⁻-Kotransporter (NKCC2) wird im distalen Nephron der Niere exprimiert. Seine Verteilung umfasst die Epithelien der medullären und kortikalen Teile der dicken aufsteigenden Henle-Schleife (Thick ascending limb, TAL) und die Macula densa. Resorptiver NaCl-Transport über den NKCC2 dient dem renalen Konzentrierungsmechanismus und reguliert systemisch auch Volumenstatus und Blutdruck. Die Aktivität des NKCC2 ist mit der Phosphorylierung seiner N-terminalen Aminosäurereste Serin 126 und Threonin 96/101 verbunden. Vermittelt wird diese durch die homologen Kinasen SPAK (SPS-related proline/alanine-rich kinase) und OSR1 (Oxidative stress responsive kinase 1), die hierzu ihrerseits phosphoryliert werden müssen. Der regulatorische Kontext dieser Kinasen ist mittlerweile gut charakterisiert. Über Mechanismen und Produkte, die den NKCC2 deaktivieren, war hingegen weniger bekannt. Ziel der Arbeit war daher zu untersuchen, welche Wege zur Deaktivierung des Transporters führen. Der intrazelluläre Sortierungsrezeptor SORLA (Sorting-protein-related receptor with A-type repeats) war zuvor in seiner Bedeutung für das Nephron charakterisiert worden. Ein SORLA-defizientes Mausmodell weist unter anderem eine stark verringerte NKCC2-Phosphorylierung auf. Unter osmotischem Stress können SORLA-defiziente Mäuse ihren Urin weniger effizient konzentrieren. Meine Resultate zeigen mit hochauflösender Technik, dass SORLA apikal im TAL lokalisiert ist und dass mit NKCC2 eine anteilige Kolokalisation besteht. Unter SORLA Defizienz war die für die NKCC2 Aktivität maßgebliche SPAK/OSR1-Phosphorylierung gegenüber dem Wildtyp nicht verändert. Jedoch war die ebenfalls im TAL exprimierte Phosphatase Calcineurin Aβ (CnAβ) per Western blot um das zweifache gesteigert. Parallel hierzu wurde immunhistochemisch die Kolokalisation von verstärktem CnAβ-Signal und NKCC2 bestätigt. Beide Befunde geben zusammen den Hinweis auf einen Bezug zwischen der reduzierten NKCC2-Phosphorylierung und der gesteigerten Präsenz von CnAβ bei SORLA Defizienz. Die parallel induzierte Überexpression von SORLA in HEK-Zellen zeigte entsprechend eine Halbierung der CnAβ Proteinmenge. SORLA steuert demzufolge sowohl die Abundanz als auch die zelluläre Verteilung der Phosphatase. Weiterhin ließ sich die Interaktion zwischen CnAβ und SORLA (intrazelluläre Domäne) mittels Co-Immunpräzipitation bzw. GST-pulldown assay nachweisen. Auch die Interaktion zwischen CnAβ und NKCC2 wurde auf diesem Weg belegt. Da allerdings weder SORLA noch NKCC2 ein spezifisches Bindungsmuster für CnAβ aufweisen, sind vermutlich intermediäre Adapterproteine bei ihrer Bindung involviert. Die pharmakologische Inhibition von CnAβ mittels Cyclosporin A (CsA; 1 h) führte bei SORLA Defizienz zur Normalisierung der NKCC2-Phosphorylierung. Entsprechend führte in vitro die Gabe von CsA bei TAL Zellen zu einer 7-fach gesteigerten NKCC2-Phosphorylierung. Zusammenfassend zeigen die Ergebnisse, dass die Phosphatase CnAβ über ihre Assoziation mit NKCC2 diesen im adluminalen Zellkompartiment deaktivieren kann. Gesteuert wird dieser Vorgang durch die Eigenschaft von SORLA, CnAβ apikal zu reduzieren und damit die adluminale Phosphorylierung und Aktivität von NKCC2 zu unterstützen. Da Calcineurin-Inhibitoren derzeit die Grundlage der immunsupprimierenden Therapie darstellen, haben die Ergebnisse eine klinische Relevanz. Angesichts der Co-Expression von SORLA und CnAβ in verschiedenen anderen Organen können die Ergebnisse auch über die Niere hinaus Bedeutung erlangen.
Obesity is a major health problem for many developing and industrial countries. Increasing rates reach almost 50 % of the population in some countries and related metabolic diseases including cardiovascular events and T2DM are challenging the health systems. Adiposity, an increase in body fat mass, is a major hallmark of obesity. Adipose tissue is long known not only to store lipids but also to influence whole-body metabolism including food intake, energy expenditure and insulin sensitivity. Adipocytes can store lipids and thereby protect other tissue from lipotoxic damage. However, if the energy intake is higher than the energy expenditure over a sustained time period, adipose tissue will expand. This can lead to an impaired adipose tissue function resulting in higher levels of plasma lipids, which can affect other tissue like skeletal muscle, finally leading to metabolic complications. Several studies showed beneficial metabolic effects of weight reduction in obese subjects immediately after weight loss. However, weight regain is frequently observed along with potential negative effects on cardiovascular risk factors and a high intra-individual response.
We performed a body weight maintenance study investigating the mechanisms of weight maintenance after intended WR. Therefore we used a low caloric diet followed by a 12-month life-style intervention. Comprehensive phenotyping including fat and muscle biopsies was conducted to investigate hormonal as well as metabolic influences on body weight regulation. In this study, we showed that weight reduction has numerous potentially beneficial effects on metabolic parameters. After 3-month WR subjects showed significant weight and fat mass reduction, lower TG levels as well as higher insulin sensitivity. Using RNA-Seq to analyse whole fat and muscle transcriptome a strong impact of weight reduction on adipose tissue gene expression was observed. Gene expression alterations over weight reduction included several cellular metabolic genes involved in lipid and glucose metabolism as well as insulin signalling and regulatory pathways. These changes were also associated with anthropometric parameters assigning body composition. Our data indicated that weight reduction leads to a decreased expression of several lipid catabolic as well as anabolic genes. Long-term body weight maintenance might be influenced by several parameters including hormones, metabolic intermediates as well as the transcriptional landscape of metabolic active tissues. Our data showed that genes involved in biosynthesis of unsaturated fatty acids might influence the BMI 18-month after a weight reduction phase. This was further supported by analysing metabolic parameters including RQ and FFA levels. We could show that subjects maintaining their lost body weight had a higher RQ and lower FFA levels, indicating increased metabolic flexibility in subjects.
Using this transcriptomic approach we hypothesize that low expression levels of lipid synthetic genes in adipose tissue together with a higher mitochondrial activity in skeletal muscle tissue might be beneficial in terms of body weight maintenance.
Spectral fingerprinting
(2015)
Current research on runoff and erosion processes, as well as an increasing demand for sustainable watershed management emphasize the need for an improved understanding of sediment dynamics. This involves the accurate assessment of erosion rates and sediment transfer, yield and origin. A variety of methods exist to capture these processes at the catchment scale. Among these, sediment fingerprinting, a technique to trace back the origin of sediment, has attracted increasing attention by the scientific community in recent years. It is a two-step procedure, based on the fundamental assumptions that potential sources of sediment can be reliably discriminated based on a set of characteristic ‘fingerprint’ properties, and that a comparison of source and sediment fingerprints allows to quantify the relative contribution of each source.
This thesis aims at further assessing the potential of spectroscopy to assist and improve the sediment fingerprinting technique. Specifically, this work focuses on (1) whether potential sediment sources can be reliably identified based on spectral features (‘fingerprints’), whether (2) these spectral fingerprints permit the quantification of relative source contribution, and whether (3) in situ derived source information is sufficient for this purpose. Furthermore, sediment fingerprinting using spectral information is applied in a study catchment to (4) identify major sources and observe how relative source contributions change between and within individual flood events. And finally, (5) spectral fingerprinting results are compared and combined with simultaneous sediment flux measurements to study sediment origin, transport and storage behaviour.
For the sediment fingerprinting approach, soil samples were collected from potential sediment sources within the Isábena catchment, a meso-scale basin in the central Spanish Pyrenees. Undisturbed samples of the upper soil layer were measured in situ using an ASD spectroradiometer and subsequently sampled for measurements in the laboratory. Suspended sediment was sampled automatically by means of ISCO samplers at the catchment as well as at the five major subcatchment outlets during flood events, and stored fine sediment from the channel bed was collected from 14 cross-sections along the main river. Artificial mixtures of known contributions were produced from source soil samples. Then, all source, sediment and mixture samples were dried and spectrally measured in the laboratory. Subsequently, colour coefficients and physically based features with relation to organic carbon, iron oxide, clay content and carbonate, were calculated from all in situ and laboratory spectra. Spectral parameters passing a number of prerequisite tests were submitted to principal component analyses to study natural clustering of samples, discriminant function analyses to observe source differentiation accuracy, and a mixing model for source contribution assessment. In addition, annual as well as flood event based suspended sediment fluxes from the catchment and its subcatchments were calculated from rainfall, water discharge and suspended sediment concentration measurements using rating curves and Quantile Regression Forests. Results of sediment flux monitoring were interpreted individually with respect to storage behaviour, compared to fingerprinting source ascriptions and combined with fingerprinting to assess their joint explanatory potential.
In response to the key questions of this work, (1) three source types (land use) and five spatial sources (subcatchments) could be reliably discriminated based on spectral fingerprints. The artificial mixture experiment revealed that while (2) laboratory parameters permitted source contribution assessment, (3) the use of in situ derived information was insufficient. Apparently, high discrimination accuracy does not necessarily imply good quantification results. When applied to suspended sediment samples of the catchment outlet, the spectral fingerprinting approach was able to (4) quantify the major sediment sources: badlands and the Villacarli subcatchment, respectively, were identified as main contributors, which is consistent with field observations and previous studies. Thereby, source contribution was found to vary both, within and between individual flood events. Also sediment flux was found to vary considerably, annually as well as seasonally and on flood event base. Storage was confirmed to play an important role in the sediment dynamics of the studied catchment, whereas floods with lower total sediment yield tend to deposit and floods with higher yield rather remove material from the channel bed. Finally, a comparison of flux measurements with fingerprinting results highlighted the fact that (5) immediate transport from sources to the catchment outlet cannot be assumed. A combination of the two methods revealed different aspects of sediment dynamics that none of the techniques could have uncovered individually.
In summary, spectral properties provide a fast, non-destructive, and cost-efficient means to discriminate and quantify sediment sources, whereas, unfortunately, straight-forward in situ collected source information is insufficient for the approach. Mixture modelling using artificial mixtures permits valuable insights into the capabilities and limitations of the method and similar experiments are strongly recommended to be performed in the future. Furthermore, a combination of techniques such as e.g. (spectral) sediment fingerprinting and sediment flux monitoring can provide comprehensive understanding of sediment dynamics.