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The Tibetan Plateau is the largest elevated landmass in the world and profoundly influences atmospheric circulation patterns such as the Asian monsoon system. Therefore this area has been increasingly in focus of palaeoenvironmental studies. This thesis evaluates the applicability of organic biomarkers for palaeolimnological purposes on the Tibetan Plateau with a focus on aquatic macrophyte-derived biomarkers. Submerged aquatic macrophytes have to be considered to significantly influence the sediment organic matter due to their high abundance in many Tibetan lakes. They can show highly 13C-enriched biomass because of their carbon metabolism and it is therefore crucial for the interpretation of δ13C values in sediment cores to understand to which extent aquatic macrophytes contribute to the isotopic signal of the sediments in Tibetan lakes and in which way variations can be explained in a palaeolimnological context. Additionally, the high abundance of macrophytes makes them interesting as potential recorders of lake water δD. Hydrogen isotope analysis of biomarkers is a rapidly evolving field to reconstruct past hydrological conditions and therefore of special relevance on the Tibetan Plateau due to the direct linkage between variations of monsoon intensity and changes in regional precipitation / evaporation balances. A set of surface sediment and aquatic macrophyte samples from the central and eastern Tibetan Plateau was analysed for composition as well as carbon and hydrogen isotopes of n-alkanes. It was shown how variable δ13C values of bulk organic matter and leaf lipids can be in submerged macrophytes even of a single species and how strongly these parameters are affected by them in corresponding sediments. The estimated contribution of the macrophytes by means of a binary isotopic model was calculated to be up to 60% (mean: 40%) to total organic carbon and up to 100% (mean: 66%) to mid-chain n-alkanes. Hydrogen isotopes of n-alkanes turned out to record δD of meteoric water of the summer precipitation. The apparent enrichment factor between water and n-alkanes was in range of previously reported ones (≈-130‰) at the most humid sites, but smaller (average: -86‰) at sites with a negative moisture budget. This indicates an influence of evaporation and evapotranspiration on δD of source water for aquatic and terrestrial plants. The offset between δD of mid- and long-chain n-alkanes was close to zero in most of the samples, suggesting that lake water as well as soil and leaf water are affected to a similar extent by those effects. To apply biomarkers in a palaeolimnological context, the aliphatic biomarker fraction of a sediment core from Lake Koucha (34.0° N; 97.2° E; eastern Tibetan Plateau) was analysed for concentrations, δ13C and δD values of compounds. Before ca. 8 cal ka BP, the lake was dominated by aquatic macrophyte-derived mid-chain n-alkanes, while after 6 cal ka BP high concentrations of a C20 highly branched isoprenoid compound indicate a predominance of phytoplankton. Those two principally different states of the lake were linked by a transition period with high abundances of microbial biomarkers. δ13C values were relatively constant for long-chain n-alkanes, while mid-chain n-alkanes showed variations between -23.5 to -12.6‰. Highest values were observed for the assumed period of maximum macrophyte growth during the late glacial and for the phytoplankton maximum during the middle and late Holocene. Therefore, the enriched values were interpreted to be caused by carbon limitation which in turn was induced by high macrophyte and primary productivity, respectively. Hydrogen isotope signatures of mid-chain n-alkanes have been shown to be able to track a previously deduced episode of reduced moisture availability between ca. 10 and 7 cal ka BP, indicated by a 20‰ shift towards higher δD values. Indications for cooler episodes at 6.0, 3.1 and 1.8 cal ka BP were gained from drops of biomarker concentrations, especially microbial-derived hopanoids, and from coincidental shifts towards lower δ13C values. Those episodes correspond well with cool events reported from other locations on the Tibetan Plateau as well as in the Northern Hemisphere. To conclude, the study of recent sediments and plants improved the understanding of factors affecting the composition and isotopic signatures of aliphatic biomarkers in sediments. Concentrations and isotopic signatures of the biomarkers in Lake Koucha could be interpreted in a palaeolimnological context and contribute to the knowledge about the history of the lake. Aquatic macrophyte-derived mid-chain n-alkanes were especially useful, due to their high abundance in many Tibetan Lakes and their ability to record major changes of lake productivity and palaeo-hydrological conditions. Therefore, they have the potential to contribute to a fuller understanding of past climate variability in this key region for atmospheric circulation systems.
In der molekularen Diagnostik besteht ein Bedarf an schnellen und spezifischen Testsystemen, die entweder für die Labordiagnostik oder in Point of Care-Umgebungen eingesetzt werden können. Um dieses Ziel zu erreichen, stehen die Miniaturisierung und Parallelisierung im Mittelpunkt des Forschungsinteresses. Die führende Methode im Bereich der DNA-Analytik ist derzeit die Realtime-PCR. Dieser Technologie sind hinsichtlich der Multiplexfähigkeit technologischen Hürden gesetzt, da derzeit nur eine Analyse von maximal vier Parametern parallel in einem Versuchsansatz erfolgen kann. Microarrays stellen hingegen die benötigten Voraussetzungen zur Verfügung, um als Werkzeuge für die Multiparameteranalyse in verschiedensten Anwendungsbereichen zu dienen. Ein Schwerpunkt dieser Arbeit war es, Multiplex-PCRs und diagnostische Microarrays zu entwickeln, die für analytische Fragestellungen eine schnelle und zuverlässige Multiparameteranalytik ermöglichen, um die bisherigen Einschränkungen aktueller Nachweisverfahren zu vermeiden. Als Anwendungen wurden zum einen ein Nachweissystem für acht relevante Geflügelpathogene zur Überwachung in der Geflügelzucht, zum anderen ein Nachweissystem zur Identifikation potentiell allergener Lebensmittelinhaltstoffe entwickelt. Neben der Entwicklung geeigneter PCR und Multiplex-PCR-Verfahren sowie spezifischer Microarrays für die Detektion der gesuchten Zielsequenzen stand auch die weiterführende Integration von DNA-Amplifikation und Microarray-Technologie im Fokus dieser Arbeit. Die OnChip-Amplifikation stellt eine Möglichkeit dar, um DNA-Analytik und Detektion in einem Reaktionsschritt zu integrieren. Entsprechend wurden die in der Arbeit entwickelten PCR- und Multiplex-PCR-Verfahren zum Nachweis potentieller allergener Lebensmittelinhaltsstoffe für die OnChip-Amplifikation adaptiert und Reaktionsbedingungen getestet, die eine Multiparameteranalyse auf dem Chip ermöglichen. Die entwickelten OnChip-PCR-Verfahren zeigten eine hohe Spezifität sowohl in Single- als auch in der Multiplex-OnChip-PCR. Eine Sensitivität von 10 Kopien bzw. <10ppm konnte in Single-OnChip-PCRs für den Nachweis allergener Lebensmittelinhaltsstoffe gezeigt werden. In Multiplex-OnChip-PCRs konnten 10-100ppm allergene Verunreinigungen spezifisch in unterschiedlichen Lebensmitteln nachgewiesen werden. Ein weiterer Schritt in Richtung einer möglichen Verwendung im Point of Care-Bereich stellt der Einsatz eines isothermalen Amplifikationsverfahrens dar. Vorteil eines solchen Verfahrens ist die Möglichkeit, auf das ansonsten benötigte Thermocycling zu verzichten. Dies vereinfacht eine Integration der OnChip-Amplifikation in mobile Analysegeräte oder Lab on Chip-Systeme und qualifiziert das Verfahren für den Einsatz in Point of Care-Umgebungen. In dieser Arbeit wurde eine noch junge isothermale Amplifikationsmethode, die helikase-abhängige Amplifikation (HDA), hinsichtlich ihrer Eignung für die Integration auf einem Microarray getestet. Hierfür konnte die bislang erste OnChip-HDA für Einzel- und Duplex-Nachweise von Pathogenen entwickelt werden.
We study buckling instabilities of filaments in biological systems. Filaments in a cell are the building blocks of the cytoskeleton. They are responsible for the mechanical stability of cells and play an important role in intracellular transport by molecular motors, which transport cargo such as organelles along cytoskeletal filaments. Filaments of the cytoskeleton are semiflexible polymers, i.e., their bending energy is comparable to the thermal energy such that they can be viewed as elastic rods on the nanometer scale, which exhibit pronounced thermal fluctuations. Like macroscopic elastic rods, filaments can undergo a mechanical buckling instability under a compressive load. In the first part of the thesis, we study how this buckling instability is affected by the pronounced thermal fluctuations of the filaments. In cells, compressive loads on filaments can be generated by molecular motors. This happens, for example, during cell division in the mitotic spindle. In the second part of the thesis, we investigate how the stochastic nature of such motor-generated forces influences the buckling behavior of filaments. In chapter 2 we review briefly the buckling instability problem of rods on the macroscopic scale and introduce an analytical model for buckling of filaments or elastic rods in two spatial dimensions in the presence of thermal fluctuations. We present an analytical treatment of the buckling instability in the presence of thermal fluctuations based on a renormalization-like procedure in terms of the non-linear sigma model where we integrate out short-wavelength fluctuations in order to obtain an effective theory for the mode of the longest wavelength governing the buckling instability. We calculate the resulting shift of the critical force by fluctuation effects and find that, in two spatial dimensions, thermal fluctuations increase this force. Furthermore, in the buckled state, thermal fluctuations lead to an increase in the mean projected length of the filament in the force direction. As a function of the contour length, the mean projected length exhibits a cusp at the buckling instability, which becomes rounded by thermal fluctuations. Our main result is the observation that a buckled filament is stretched by thermal fluctuations, i.e., its mean projected length in the direction of the applied force increases by thermal fluctuations. Our analytical results are confirmed by Monte Carlo simulations for buckling of semiflexible filaments in two spatial dimensions. We also perform Monte Carlo simulations in higher spatial dimensions and show that the increase in projected length by thermal fluctuations is less pronounced than in two dimensions and strongly depends on the choice of the boundary conditions. In the second part of this work, we present a model for buckling of semiflexible filaments under the action of molecular motors. We investigate a system in which a group of motors moves along a clamped filament carrying a second filament as a cargo. The cargo-filament is pushed against the wall and eventually buckles. The force-generating motors can stochastically unbind and rebind to the filament during the buckling process. We formulate a stochastic model of this system and calculate the mean first passage time for the unbinding of all linking motors which corresponds to the transition back to the unbuckled state of the cargo filament in a mean-field model. Our results show that for sufficiently short microtubules the movement of kinesin-I-motors is affected by the load force generated by the cargo filament. Our predictions could be tested in future experiments.
Foreland-basin systems are excellent archives to decipher the feedbacks between surface and tectonic processes in orogens. The sedimentary architecture of a foreland-basin system reflects the balance between tectonic subsidence causing long-term accommodation space and sediment influx corresponding to efficiency of erosion and mass-redistribution processes. In order to explore the effects of climatic and tectonic forcing in such a system, I investigated the Oligo-Miocene foreland-basin sediments of the southern Alborz mountains, an intracontinental orogen in northern Iran, related to the Arabia-Eurasia continental collision. This work includes absolute dating methods such as 40Ar/39Ar and zircon (U-Th)/He thermochronology, magnetostratigraphy, sedimentological analysis, sandstone and conglomerate provenance study, carbon and oxygen isotope analysis, and clay mineralogy study. Results show a systematic correlation between coarsening-upward cycles and sediment accumulation rates in the basin on 105 to 106yr time scales. During thrust loading phases, the coarse-grained fraction supplied by the uplifting range is stored in the proximal part of the basin (sedimentary facies retrogradation), while fine-grained sediments are deposited in distal sectors. Variations in sediment provenance during these phases of enhanced tectonic activity give evidence for erosional unroofing phases and/or drainage-reorganization events. In addition, enhanced tectonic activity promoted the growth of topography and associated orographic barrier effects, as demonstrated by sedimentologic indicators and the analysis of stable C and O isotopes from calcareous paleosols and lacustrine/palustrine samples. Extensive progradation of coarse-grained deposits occurs during phases of decreased subsidence, when the coarse-grained fraction supplied by the uplifting range cannot be completely stored in the proximal part of the basin. In this environment, a reduction in basin subsidence is associated with laterally stacked fluvial channel deposits, and is related to intra-foreland uplift, as documented by growth strata, tectonic tilting, and sediment reworking. Increase in sediment accumulation rate associated with progradation of vertically-stacked coarse-grained fluvial channels also occurs. Paleosol O-isotope data shows that this increase is related to wetter climatic phases, suggesting that surface processes are more efficient and exhumation rates increase, giving rise to a positive feedback. Furthermore, isotopic and sedimentologic data show that starting from 10-9 Ma, climate became less arid with an increase in seasonality of precipitation. Because important changes were also recorded in the Mediterranean Sea and Asia at that time, the evidence for climatic variability observed in the Alborz mountains most likely reflects changes in Northern Hemisphere atmospheric circulation patterns. This study has additional implications for the evolution of the Alborz mountains and the Arabia-Eurasia continental collision zone. At the orogenic scale, the locus of deformation did not move steadily southward, but stepped forward and backward since Oligocene time. In particular, from ~ 17.5 to 6.2 Ma the orogen grew by a combination of frontal accretion and wedge-internal deformation on time scales of ca. 0.7 to 2 m.y. Moreover, the provenance data suggest that prior to 10-9 Ma the shortening direction changed from NW-SE to NNE-SSW, in agreement with structural data. On the scale of the entire collision zone, the evolution of the studied basins and adjacent mountain ranges suggests a new geodynamic model for the evolution of the Arabia-Eurasia continental collision zone. Numerous sedimentary basins in the Alborz mountains and in other locations of the Arabia-Eurasia collision zone record a change from a tensional (transtensional) to a compressional (transpressional) tectonic setting by ~ 36 Ma. I interpret this to reflect the onset of subduction of the stretched Arabian continental lithosphere beneath central Iran, leading to moderate plate coupling and lower- and upper-plate deformation (soft continental collision). The increase in deformation rates in the southern Alborz mountains from ~ 17.5 Ma suggests that significant upper-plate deformation must have started by the early Miocene most likely in response to an increase in degree of plate coupling. I suggest that this was related to the subduction of thicker Arabian continental lithosphere and the consequent onset of hard continental collision. This model reconciles the apparent lag time of 15-20 m.y between the late Eocene to early Oligocene age for the initial Arabia-Eurasia continental collision and the onset of widespread deformation across the collision zone to the north in early to late Miocene time.
Classical semiconductor physics has been continuously improving electronic components such as diodes, light-emitting diodes, solar cells and transistors based on highly purified inorganic crystals over the past decades. Organic semiconductors, notably polymeric, are a comparatively young field of research, the first light-emitting diode based on conjugated polymers having been demonstrated in 1990. Polymeric semiconductors are of tremendous interest for high-volume, low-cost manufacturing ("printed electronics"). Due to their rather simple device structure mostly comprising only one or two functional layers, polymeric diodes are much more difficult to optimize compared to small-molecular organic devices. Usually, functions such as charge injection and transport are handled by the same material which thus needs to be highly optimized. The present work contributes to expanding the knowledge on the physical mechanisms determining device performance by analyzing the role of charge injection and transport on device efficiency for blue and white-emitting devices, based on commercially relevant spiro-linked polyfluorene derivatives. It is shown that such polymers can act as very efficient electron conductors and that interface effects such as charge trapping play the key role in determining the overall device efficiency. This work contributes to the knowledge of how charges drift through the polymer layer to finally find neutral emissive trap states and thus allows a quantitative prediction of the emission color of multichromophoric systems, compatible with the observed color shifts upon driving voltage and temperature variation as well as with electrical conditioning effects. In a more methodically oriented part, it is demonstrated that the transient device emission observed upon terminating the driving voltage can be used to monitor the decay of geminately-bound species as well as to determine trapped charge densities. This enables direct comparisons with numerical simulations based on the known properties of charge injection, transport and recombination. The method of charge extraction under linear increasing voltages (CELIV) is investigated in some detail, correcting for errors in the published approach and highlighting the role of non-idealized conditions typically present in experiments. An improved method is suggested to determine the field dependence of charge mobility in a more accurate way. Finally, it is shown that the neglect of charge recombination has led to a misunderstanding of experimental results in terms of a time-dependent mobility relaxation.
Das homotrimere Tailspikeadhäsin des Bakteriophagen P22 ist ein etabliertes Modellsystem, dessen Faltung, Assemblierung und Stabilität in vivo und in vitro umfassend charakterisiert ist. Das zentrale Strukturmotiv des Proteins ist eine parallele beta-Helix mit 13 Windungen, die von einer N‑terminalen Kapsidbindedomäne und einer C‑terminalen Trimerisierungsdomäne flankiert wird. Jede Windung beinhaltet drei kurze beta-Stränge, die durch turns und loops unterschiedlicher Länge verbunden sind. Durch den sich strukturell wiederholenden, spulenförmigen Aufbau formen beta-Stränge benachbarter Windungen elongierte beta-Faltblätter. Das Lumen der beta-Helix beinhaltet größtenteils hydrophobe Seitenketten, welche linear und sehr regelmäßig entlang der Längsachse gestapelt sind. Eine hoch repetitive Struktur, ausgedehnte beta-Faltblätter und die regelmäßige Anordnung von ähnlichen oder identischen Seitenketten entlang der beta-Faltblattachse sind ebenfalls typische Kennzeichen von Amyloidfibrillen, die bei Proteinfaltungskrankheiten wie Alzheimer, der Creutzfeld-Jakob-Krankheit, Chorea Huntington und Typ-II-Diabetes gebildet werden. Es wird vermutet, dass die hohe Stabilität des Tailspikeproteins und auch die der Amyloidfibrille durch Seitenkettenstapelung, einem geordneten Netzwerk von Wasserstoffbrückenbindungen und den rigiden, oligomeren Verbund bedingt ist. Um den Einfluss der Seitenkettenstapelung auf die Stabilität, Faltung und Struktur des P22 Tailspikeproteins zu untersuchen, wurden sieben Valine in einem im Lumen der beta-Helix begrabenen Seitenkettenstapel gegen das kleinere und weniger hydrophobe Alanin und das voluminösere Leucin substituiert. Der Einfluss der Mutationen wurde anhand zweier Tailspikevarianten, dem trimeren, N‑terminal verkürzten TSPdeltaN‑Konstrukt und der monomeren, isolierten beta-Helix Domäne analysiert. Generell wurde in den Experimenten deutlich, dass Mutationen zu Alanin stärkere Effekte auslösen als Mutationen zu Leucin. Die dichte und hydrophobe Packung im Kern der beta-Helix bildet somit die Basis für Stabilität und Faltung des Proteins. Anhand hoch aufgelöster Kristallstrukturen jeweils zweier Alanin‑ und Leucin‑Mutanten konnte verdeutlicht werden, dass das Strukturmotiv der parallelen beta-Helix stark formbar ist und mutationsbedingte Änderungen des Seitenkettenvolumens durch kleine und lokale Verschiebung der Haupt‑ und Seitenketten ausgeglichen werden, sodass mögliche Kavitäten gefüllt und sterische Spannung abgebaut werden können. Viele Mutanten zeigten in vivo und in vitro einen temperatursensitiven Faltungsphänotyp (temperature sensitive for folding, tsf), d.h. bei Temperaturerhöhung waren die Ausbeuten des N‑terminal verkürzten Trimers im Vergleich zum Wildtyp deutlich verringert. Weiterführende Experimente zeigten, dass der tsf‑Phänotyp durch die Beeinflussung unterschiedlicher Stadien des Reifungsprozesses oder auch durch die Verminderung der kinetischen Stabilität des nativen Trimers ausgelöst wurde. Durch Untersuchungen am vollständigen und am N‑terminal verkürzten Wildtypprotein wurde gezeigt, dass die Entfaltungsreaktion des Tailspiketrimers komplex ist. Die Verläufe der Kinetiken folgen zwar einem apparenten Zweizustandsverhalten, jedoch sind bei Darstellung der Entfaltungsäste im Chevronplot die Abhängigkeiten der Geschwindigkeitskonstanten vom Denaturierungsmittel nicht linear, sondern in unterschiedliche Richtungen gewölbt. Dieses Verhalten könnte durch ein hoch energetisches Entfaltungsintermediat, einen breiten Übergangsbereich oder parallele Entfaltungswege hervorgerufen sein. Mit Hilfe der monomeren, isolierten beta-Helix Domäne, bei der die N‑terminale Capsidbindedomäne und die C‑terminale Trimerisierungsdomäne deletiert sind und welche als unabhängige Faltungseinheit fungiert, wurde gezeigt, dass alle Mutanten im Harnstoff‑induzierten Gleichgewicht analog zum Wildtypprotein einem Zweizustandsverhalten mit vergleichbaren Kooperativitäten folgen. Die konformationellen Stabilitäten von in der beta-Helix zentral gelegenen Alanin‑ und Leucin‑Mutanten sind stark vermindert, während Mutationen in äußeren Bereichen der Domäne keinen Einfluss auf die Stabilität der beta-Helix haben. Bei Verlängerung der Inkubationszeiten der Gleichgewichtsexperimente konnte die langsame Bildung von Aggregaten im Übergangsbereich der destabilisierten Mutanten detektiert werden. Die in der Arbeit erlangten Erkenntnisse lassen vermuten, dass die isolierte beta-Helix einem für die Reifung des Tailspikeproteins entscheidenden thermolabilen Faltungsintermediat auf Monomerebene sehr ähnlich ist. Im Intermediat ist ein zentraler Kern, der die Windungen 4 bis 7 und die „Rückenflosse“ beinhaltet, stabilitätsbestimmend. Dieser Kern könnte als Faltungsnukleus dienen, an den sich sequenziell weitere Helixwindungen anlagern und im Zuge der „Monomerreifung“ kompaktieren.
Der ubiquitär exprimierte, multifunktionale Glucosetransporter GLUT8 gehört zur Klasse III der Familie der passiven Glucosetransporter, die aus insgesamt 14 Proteinen besteht. Die fünf Mitglieder der Klasse IIII unterscheiden sich strukturell leicht von den Mitgliedern der Klasse I und II (Joost und Thorens, 2001). GLUT8 besitzt ein N-terminales Dileucin-Motiv, das Teil eines [DE]XXXL[LI] Motivs ist, welches für die Sortierung des Transporters in späte Endosomen und Lysosomen verantwortlich ist (Augustin et al., 2005). Da bis heute kein Signal identifiziert wurde, das eine Translokation des Transporters zur Plasmamembran auslöst, wird eine intrazelluläre Funktion von GLUT8 vermutet (Widmer et al., 2005). Im Rahmen der vorliegenden Arbeit wurde die intrazelluläre Funktion des Transporters in der Regulation der Glucosehomöostase des Körpers durch Analyse einer Slc2a8-knockout-Maus untersucht. Die homozygote Deletion des Transporters erbrachte lebensfähige Nachkommen, die sich augenscheinlich nicht von ihren Wildtyp-Geschwistern unterschieden. Allerdings wurde bei Verpaarungen heterozygoter Mäuse eine verminderte Anzahl an Slc2a8-/--Nachkommen beobachtet, die signifikant von der erwarteten Mendel’schen Verteilung abwich. Da Slc2a8 die höchste mRNA-Expression in den Testes aufwies und die Überprüfung der Fertilität mittels verschiedener homozygoter Verpaarungen eine Störung der weiblichen Fortpflanzungsfähigkeit ausschloss, wurden die Spermatozoen der Slc2a8-/--Mäuse eingehender untersucht. Als Ursache für die verringerte Anzahl von Slc2a8-/--Geburten wurde eine verminderte Prozentzahl motiler Slc2a8-/--Spermien ermittelt, die durch eine unzureichende mitochondriale Kondensation in den Spermien bedingt war. Diese Veränderung war mit einem reduzierten mitochondrialen Membranpotential assoziiert, was eine verminderte ATP-Produktion nach sich zog. Somit scheint GLUT8 in den Spermien an einem intrazellulären Transportprozess beteiligt zu sein, der einen Einfluss auf die oxidative Phosphorylierung der Mitochondrien ausübt. Im Gehirn wurde Slc2a8 besonders stark im Hippocampus exprimiert, der in der Regulation von körperlicher Aktivität, Explorationsverhalten, Erinnerungs- und Lernprozessen sowie Angst- und Stressreaktionen eine Rolle spielt. Außerdem wurde GLUT8 im Hypothalamus nachgewiesen, der unter anderem an der Regulation der Nahrungsaufnahme beteiligt ist. Die Slc2a8-/--Mäuse zeigten im Vergleich zu ihren Slc2a8+/+-Geschwistern eine signifikant gesteigerte körperliche Aktivität, die zusammen mit der von Membrez et al. (2006) publizierten erhöhten Zellproliferation im Hippocampus auf eine Nährstoffunterversorgung dieses Areals hindeutet. Die Nahrungsaufnahme war in Abwesenheit von GLUT8 nicht verändert, was zusammen mit dem nur geringfügig niedrigeren Körpergewicht der Slc2a8-/--Mäuse eine Funktion von GLUT8 im Glucose-sensing der Glucose-sensitiven Neurone des Gehirns ausschließt. Das leicht reduzierte Körpergewicht der Slc2a8-/--Mäuse ließ sich keinem bestimmten Organ- oder Gewebetyp zuordnen, sondern schien durch eine marginale Gewichtsreduktion aller untersuchten Gewebe bedingt zu sein. Zusammen mit den erniedrigten Blutglucosespiegeln und der anscheinend gesteigerten Lebenserwartung zeigten die Slc2a8-/--Mäuse Symptome einer leichten Nährstoffunterversorgung. GLUT8 scheint daher am Transport von Zuckerderivaten, die während des lysosomalen/endosomalen Abbaus von Glykoproteinen anfallen, beteiligt zu sein. Die so wiederaufbereiteten Zucker dienen dem Körper offenbar als zusätzliche Energiequelle.
This work presents the synthesis and the self-assembly of symmetrical amphiphilic ABA and BAB triblock copolymers in dilute, semi-concentrated and highly concentrated aqueous solution. A series of new bifunctional bistrithiocarbonates as RAFT agents was used to synthesise these triblock copolymers, which are characterised by a long hydrophilic middle block and relatively small, but strongly hydrophobic end blocks. As hydrophilic A blocks, poly(N-isopropylacrylamide) (PNIPAM) and poly(methoxy diethylene glycol acrylate) (PMDEGA) were employed, while as hydrophobic B blocks, poly(4-tert-butyl styrene), polystyrene, poly(3,5-dibromo benzyl acrylate), poly(2-ethylhexyl acrylate), and poly(octadecyl acrylate) were explored as building blocks with different hydrophobicities and glass transition temperatures. The five bifunctional trithiocarbonates synthesised belong to two classes: the first are RAFT agents, which position the active group of the growing polymer chain at the outer ends of the polymer (Z-C(=S)-S-R-S-C(=S)-Z, type I). The second class places the active groups in the middle of the growing polymer chain (R-S-C(=S)-Z-C(=S)-S-R, type II). These RAFT agents enable the straightforward synthesis of amphiphilic triblock copolymers in only two steps, allowing to vary the nature of the hydrophobic blocks as well as the length of the hydrophobic and hydrophilic blocks broadly with good molar mass control and narrow polydispersities. Specific side reactions were observed among some RAFT agents including the elimination of ethylenetrithiocarbonate in the early stage of the polymerisation of styrene mediated by certain agents of the type II, while the use of the RAFT agents of type I resulted in retardation of the chain extension of PNIPAM with styrene. These results underline the need of a careful choice of RAFT agents for a given task. The various copolymers self-assemble in dilute and semi-concentrated aqueous solution into small flower-like micelles. No indication for the formation of micellar clusters was found, while only at high concentration, physical hydrogels are formed. The reversible thermoresponsive behaviour of the ABA and BAB type copolymer solutions in water with A made of PNIPAM was examined by turbidimetry and dynamic light scattering (DLS). The cloud point of the copolymers was nearly identical to the cloud point of the homopolymer and varied between 28-32 °C with concentrations from 0.01 to 50 wt%. This is attributed to the formation of micelles where the hydrophobic blocks are shielded from a direct contact with water, so that the hydrophobic interactions of the copolymers are nearly the same as for pure PNIPAM. Dynamic light scattering measurements showed the presence of small micelles at ambient temperature. The aggregate size dramatically increased above the cloud point, indicating a change of aggregate morphology into clusters due to the thermosensitivity of the PNIPAM block. The rheological behaviour of the amphiphilic BAB triblock copolymers demonstrated the formation of hydrogels at high concentrations, typically above 30-35 wt%. The minimum concentration to induce hydrogels decreased with the increasing glass transition temperatures and increasing length of the end blocks. The weak tendency to form hydrogels was attributed to a small share of bridged micelles only, due to the strong segregation regime occurring. In order to learn about the role of the nature of the thermoresponsive block for the aggregation, a new BAB triblock copolymer consisting of short polystyrene end blocks and PMDEGA as stimuli-responsive middle block was prepared and investigated. Contrary to PNIPAM, dilute aqueous solutions of PMDEGA and of its block copolymers showed reversible phase transition temperatures characterised by a strong dependence on the polymer composition. Moreover, the PMDEGA block copolymer allowed the formation of physical hydrogels at lower concentration, i.e. from 20 wt%. This result suggests that PMDEGA has a higher degree of water-swellability than PNIPAM.
‘Heterosis’ is a term used in genetics and breeding referring to hybrid vigour or the superiority of hybrids over their parents in terms of traits such as size, growth rate, biomass, fertility, yield, nutrient content, disease resistance or tolerance to abiotic and abiotic stress. Parental plants which are two different inbred (pure) lines that have desired traits are crossed to obtain hybrids. Maximum heterosis is observed in the first generation (F1) of crosses. Heterosis has been utilised in plant and animal breeding programs for at least 90 years: by the end of the 21st century, 65% of worldwide maize production was hybrid-based. Generally, it is believed that an understanding of the molecular basis of heterosis will allow the creation of new superior genotypes which could either be used directly as F1 hybrids or form the basis for the future breeding selection programmes. Two selected accessions of a research model plant Arabidopsis thaliana (thale cress) were crossed to obtain hybrids. These typically exhibited a 60-80% increase of biomass when compared to the average weight of both parents. This PhD project focused on investigating the role of selected regulatory genes given their potentially key involvement in heterosis. In the first part of the project, the most appropriate developmental stage for this heterosis study was determined by metabolite level measurements and growth observations in parents and hybrids. At the selected stage, around 60 candidate regulatory genes (i.e. differentially expressed in hybrids when compared to parents) were identified. Of these, the majority were transcription factors, genes that coordinate the expression of other genes. Subsequent expression analyses of the candidate genes in biomass-heterotic hybrids of other Arabidopsis accessions revealed a differential expression in a gene subset, highlighting their relevance for heterosis. Moreover, a fraction of the candidate regulatory genes were found within DNA regions closely linked to the genes that underlie the biomass or growth heterosis. Additional analyses to validate the role of selected candidate regulatory genes in heterosis appeared insufficient to establish their role in heterosis. This uncovered a need for using novel approaches as discussed in the thesis. Taken together, the work provided an insight into studies on the molecular mechanisms underlying heterosis. Although studies on heterosis date back to more than one hundred years, this project as many others revealed that more investigations will be needed to uncover this phenomenon.
In the first section of the thesis graphitic carbon nitride was for the first time synthesised using the high-temperature condensation of dicyandiamide (DCDA) – a simple molecular precursor – in a eutectic salt melt of lithium chloride and potassium chloride. The extent of condensation, namely next to complete conversion of all reactive end groups, was verified by elemental microanalysis and vibrational spectroscopy. TEM- and SEM-measurements gave detailed insight into the well-defined morphology of these organic crystals, which are not based on 0D or 1D constituents like known molecular or short-chain polymeric crystals but on the packing motif of extended 2D frameworks. The proposed crystal structure of this g-C3N4 species was derived in analogy to graphite by means of extensive powder XRD studies, indexing and refinement. It is based on sheets of hexagonally arranged s-heptazine (C6N7) units that are held together by covalent bonds between C and N atoms. These sheets stack in a graphitic, staggered fashion adopting an AB-motif, as corroborated by powder X-ray diffractometry and high-resolution transmission electron microscopy. This study was contrasted with one of many popular – yet unsuccessful – approaches in the last 30 years of scientific literature to perform the condensation of an extended carbon nitride species through synthesis in the bulk. The second section expands the repertoire of available salt melts introducing the lithium bromide and potassium bromide eutectic as an excellent medium to obtain a new phase of graphitic carbon nitride. The combination of SEM, TEM, PXRD and electron diffraction reveals that the new graphitic carbon nitride phase stacks in an ABA’ motif forming unprecedentedly large crystals. This section seizes the notion of the preceding chapter, that condensation in a eutectic salt melt is the key to obtain a high degree of conversion mainly through a solvatory effect. At the close of this chapter ionothermal synthesis is seen established as a powerful tool to overcome the inherent kinetic problems of solid state reactions such as incomplete polymerisation and condensation in the bulk especially when the temperature requirement of the reaction in question falls into the proverbial “no man’s land” of classical solvents, i.e. above 250 to 300 °C. The following section puts the claim to the test, that the crystalline carbon nitrides obtained from a salt melt are indeed graphitic. A typical property of graphite – namely the accessibility of its interplanar space for guest molecules – is transferred to the graphitic carbon nitride system. Metallic potassium and graphitic carbon nitride are converted to give the potassium intercalation compound, K(C6N8)3 designated according to its stoichiometry and proposed crystal structure. Reaction of the intercalate with aqueous solvents triggers the exfoliation of the graphitic carbon nitride material and – for the first time – enables the access of singular (or multiple) carbon nitride sheets analogous to graphene as seen in the formation of sheets, bundles and scrolls of carbon nitride in TEM imaging. The thus exfoliated sheets form a stable, strongly fluorescent solution in aqueous media, which shows no sign in UV/Vis spectroscopy that the aromaticity of individual sheets was subject to degradation. The final section expands on the mechanism underlying the formation of graphitic carbon nitride by literally expanding the distance between the covalently linked heptazine units which constitute these materials. A close examination of all proposed reaction mechanisms to-date in the light of exhaustive DSC/MS experiments highlights the possibility that the heptazine unit can be formed from smaller molecules, even if some of the designated leaving groups (such as ammonia) are substituted by an element, R, which later on remains linked to the nascent heptazine. Furthermore, it is suggested that the key functional groups in the process are the triazine- (Tz) and the carbonitrile- (CN) group. On the basis of these assumptions, molecular precursors are tailored which encompass all necessary functional groups to form a central heptazine unit of threefold, planar symmetry and then still retain outward functionalities for self-propagated condensation in all three directions. Two model systems based on a para-aryl (ArCNTz) and para-biphenyl (BiPhCNTz) precursors are devised via a facile synthetic procedure and then condensed in an ionothermal process to yield the heptazine based frameworks, HBF-1 and HBF-2. Due to the structural motifs of their molecular precursors, individual sheets of HBF-1 and HBF-2 span cavities of 14.2 Å and 23.0 Å respectively which makes both materials attractive as potential organic zeolites. Crystallographic analysis confirms the formation of ABA’ layered, graphitic systems, and the extent of condensation is confirmed as next-to-perfect by elemental analysis and vibrational spectroscopy.
Recent years witnessed a vast advent of stalagmites as palaeoclimate archives. The multitude of geochemical and physical proxies and a promise of a precise and accurate age model greatly appeal to palaeoclimatologists. Although substantial progress was made in speleothem-based palaeoclimate research and despite high-resolution records from low-latitudinal regions, proving that palaeo-environmental changes can be archived on sub-annual to millennial time scales our comprehension of climate dynamics is still fragmentary. This is in particular true for the summer monsoon system on the Indian subcontinent. The Indian summer monsoon (ISM) is an integral part of the intertropical convergence zone (ITCZ). As this rainfall belt migrates northward during boreal summer, it brings monsoonal rainfall. ISM strength depends however on a variety of factors, including snow cover in Central Asia and oceanic conditions in the Indic and Pacific. Presently, many of the factors influencing the ISM are known, though their exact forcing mechanism and mutual relations remain ambiguous. Attempts to make an accurate prediction of rainfall intensity and frequency and drought recurrence, which is extremely important for South Asian countries, resemble a puzzle game; all interaction need to fall into the right place to obtain a complete picture. My thesis aims to create a faithful picture of climate change in India, covering the last 11,000 ka. NE India represents a key region for the Bay of Bengal (BoB) branch of the ISM, as it is here where the monsoon splits into a northwestward and a northeastward directed arm. The Meghalaya Plateau is the first barrier for northward moving air masses and receives excessive summer rainfall, while the winter season is very dry. The proximity of Meghalaya to the Tibetan Plateau on the one hand and the BoB on the other hand make the study area a key location for investigating the interaction between different forcings that governs the ISM. A basis for the interpretation of palaeoclimate records, and a first important outcome of my thesis is a conceptual model which explains the observed pattern of seasonal changes in stable isotopes (d18O and d2H) in rainfall. I show that although in tropical and subtropical regions the amount effect is commonly called to explain strongly depleted isotope values during enhanced rainfall, alone it cannot account for observed rainwater isotope variability in Meghalaya. Monitoring of rainwater isotopes shows no expected negative correlation between precipitation amount and d18O of rainfall. In turn I find evidence that the runoff from high elevations carries an inherited isotopic signature into the BoB, where during the ISM season the freshwater builds a strongly depleted plume on top of the marine water. The vapor originating from this plume is likely to memorize' and transmit further very negative d18O values. The lack of data does not allow for quantication of this plume effect' on isotopes in rainfall over Meghalaya but I suggest that it varies on seasonal to millennial timescales, depending on the runoff amount and source characteristics. The focal point of my thesis is the extraction of climatic signals archived in stalagmites from NE India. High uranium concentration in the stalagmites ensured excellent age control required for successful high-resolution climate reconstructions. Stable isotope (d18O and d13C) and grey-scale data allow unprecedented insights into millennial to seasonal dynamics of the summer and winter monsoon in NE India. ISM strength (i. e. rainfall amount) is recorded in changes in d18Ostalagmites. The d13C signal, reflecting drip rate changes, renders a powerful proxy for dry season conditions, and shows similarities to temperature-related changes on the Tibetan Plateau. A sub-annual grey-scale profile supports a concept of lower drip rate and slower stalagmite growth during dry conditions. During the Holocene, ISM followed a millennial-scale decrease of insolation, with decadal to centennial failures resulting from atmospheric changes. The period of maximum rainfall and enhanced seasonality corresponds to the Holocene Thermal Optimum observed in Europe. After a phase of rather stable conditions, 4.5 kyr ago, the strengthening ENSO system dominated the ISM. Strong El Nino events weakened the ISM, especially when in concert with positive Indian Ocean dipole events. The strongest droughts of the last 11 kyr are recorded during the past 2 kyr. Using the advantage of a well-dated stalagmite record at hand I tested the application of laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) to detect sub-annual to sub-decadal changes in element concentrations in stalagmites. The development of a large ablation cell allows for ablating sample slabs of up to 22 cm total length. Each analyzed element is a potential proxy for different climatic parameters. Combining my previous results with the LAICP- MS-generated data shows that element concentration depends not only on rainfall amount and associated leaching from the soil. Additional factors, like biological activity and hydrogeochemical conditions in the soil and vadose zone can eventually affect the element content in drip water and in stalagmites. I present a theoretical conceptual model for my study site to explain how climatic signals can be transmitted and archived in stalagmite carbonate. Further, I establish a first 1500 year long element record, reconstructing rainfall variability. Additionally, I hypothesize that volcanic eruptions, producing large amounts of sulfuric acid, can influence soil acidity and hence element mobilization.
Submarine landslides can generate local tsunamis posing a hazard to human lives and coastal facilities. Two major related problems are: (i) quantitative estimation of tsunami hazard and (ii) early detection of the most dangerous landslides. This thesis focuses on both those issues by providing numerical modeling of landslide-induced tsunamis and by suggesting and justifying a new method for fast detection of tsunamigenic landslides by means of tiltmeters. Due to the proximity to the Sunda subduction zone, Indonesian coasts are prone to earthquake, but also landslide tsunamis. The aim of the GITEWS-project (German-Indonesian Tsunami Early Warning System) is to provide fast and reliable tsunami warnings, but also to deepen the knowledge about tsunami hazards. New bathymetric data at the Sunda Arc provide the opportunity to evaluate the hazard potential of landslide tsunamis for the adjacent Indonesian islands. I present nine large mass movements in proximity to Sumatra, Java, Sumbawa and Sumba, whereof the largest event displaced 20 km³ of sediments. Using numerical modeling, I compute the generated tsunami of each event, its propagation and runup at the coast. Moreover, I investigate the age of the largest slope failures by relating them to the Great 1977 Sumba earthquake. Continental slopes off northwest Europe are well known for their history of huge underwater landslides. The current geological situation west of Spitsbergen is comparable to the continental margin off Norway after the last glaciation, when the large tsunamigenic Storegga slide took place. The influence of Arctic warming on the stability of the Svalbard glacial margin is discussed. Based on new geophysical data, I present four possible landslide scenarios and compute the generated tsunamis. Waves of 6 m height would be capable of reaching northwest Europe threatening coastal areas. I present a novel technique to detect large submarine landslides using an array of tiltmeters, as a possible tool in future tsunami early warning systems. The dislocation of a large amount of sediment during a landslide produces a permanent elastic response of the earth. I analyze this response with a mathematical model and calculate the theoretical tilt signal. Applications to the hypothetical Spitsbergen event and the historical Storegga slide show tilt signals exceeding 1000 nrad. The amplitude of landslide tsunamis is controlled by the product of slide volume and maximal velocity (slide tsunamigenic potential). I introduce an inversion routine that provides slide location and tsunamigenic potential, based on tiltmeter measurements. The accuracy of the inversion and of the estimated tsunami height near the coast depends on the noise level of tiltmeter measurements, the distance of tiltmeters from the slide, and the slide tsunamigenic potential. Finally, I estimate the applicability scope of this method by employing it to known landslide events worldwide.
The present thesis aims to introduce process-based model for species range dynamics that can be fitted to abundance data. For this purpose, the well-studied Proteaceae species of the South African Cape Floristic Region (CFR) offer a great data set to fit process-based models. These species are subject to wildflower harvesting and environmental threats like habitat loss and climate change. The general introduction of this thesis presents shortly the available models for species distribution modelling. Subsequently, it presents the feasibility of process-based modelling. Finally, it introduces the study system as well as the objectives and layout. In Chapter 1, I present the process-based model for range dynamics and a statistical framework to fit it to abundance distribution data. The model has a spatially-explicit demographic submodel (describing dispersal, reproduction, mortality and local extinction) and an observation submodel (describing imperfect detection of individuals). The demographic submodel links species-specific habitat models describing the suitable habitat and process-based demographic models that consider local dynamics and anemochoric seed dispersal between populations. After testing the fitting framework with simulated data, I applied it to eight Proteaceae species with different demographic properties. Moreover, I assess the role of two other demographic mechanisms: positive (Allee effects) and negative density-dependence. Results indicate that Allee effects and overcompensatory local dynamics (including chaotic behaviour) seem to be important for several species. Most parameter estimates quantitatively agreed with independent data. Hence, the presented approach seemed to suit the demand of investigating non-equilibrium scenarios involving wildflower harvesting (Chapter 2) and environmental change (Chapter 3). The Chapter 2 addresses the impacts of wildflower harvesting. The chapter includes a sensitivity analysis over multiple spatial scales and demographic properties (dispersal ability, strength of Allee effects, maximum reproductive rate, adult mortality, local extinction probability and carrying capacity). Subsequently, harvesting effects are investigated on real case study species. Plant response to harvesting showed abrupt threshold behavior. Species with short-distance seed dispersal, strong Allee effects, low maximum reproductive rate, high mortality and high local extinction are most affected by harvesting. Larger spatial scales benefit species response, but the thresholds become sharper. The three case study species supported very low to moderate harvesting rates. Summarizing, demographic knowledge about the study system and careful identification of the spatial scale of interest should guide harvesting assessments and conservation of exploited species. The sensitivity analysis’ results can be used to qualitatively assess harvesting impacts for poorly studied species. I investigated in Chapter 3 the consequences of past habitat loss, future climate change and their interaction on plant response. I use the species-specific estimates of the best model describing local dynamics obtained in Chapter 1. Both habitat loss and climate change had strong negative impacts on species dynamics. Climate change affected mainly range size and range filling due to habitat reductions and shifts combined with low colonization. Habitat loss affected mostly local abundances. The scenario with both habitat loss and climate change was the worst for most species. However, this impact was better than expected by simple summing of separate effects of habitat loss and climate change. This is explained by shifting ranges to areas less affected by humans. Range size response was well predicted by the strength of environmental change, whereas range filling and local abundance responses were better explained by demographic properties. Hence, risk assessments under global change should consider demographic properties. Most surviving populations were restricted to refugia, serving as key conservation focus.The findings obtained for the study system as well as the advantages, limitations and potentials of the model presented here are further discussed in the General Discussion. In summary, the results indicate that 1) process-based demographic models for range dynamics can be fitted to data; 2) demographic processes improve species distribution models; 3) different species are subject to different processes and respond differently to environmental change and exploitation; 4) density regulation type and Allee effects should be considered when investigating range dynamics of species; 5) the consequences of wildflower harvesting, habitat loss and climate change could be disastrous for some species, but impacts vary depending on demographic properties; 6) wildflower harvesting impacts varies over spatial scale; 7) The effects of habitat loss and climate change are not always additive.
After the epoch of reionisation the intergalactic medium (IGM) is kept at a high photoionisation level by the cosmic UV background radiation field. Primarily composed of the integrated contribution of quasars and young star forming galaxies, its intensity is subject to spatial and temporal fluctuations. In particular in the vicinity of luminous quasars, the UV radiation intensity grows by several orders of magnitude. Due to an enhanced UV radiation up to a few Mpc from the quasar, the ionised hydrogen fraction significantly increases and becomes visible as a reduced level of absorption in the HI Lyman alpha (Ly-alpha) forest. This phenomenon is known as the proximity effect and it is the main focus of this thesis. Modelling the influence on the IGM of the quasar radiation, one is able to determine the UV background intensity at a specific frequency (J_nu_0), or equivalently, its photoionisation rate (Gamma_b). This is of crucial importance for both theoretical and observational cosmology. Thus far, the proximity effect has been investigated primarily by combining the signal of large samples of quasars, as it has been regarded as a statistical phenomenon. Only a handful of studies tried to measure its signature on individual lines of sight, albeit focusing on one sight line only. Our aim is to perform a systematic investigation of large samples of quasars searching for the signature of the proximity effect, with a particular emphasis on its detection on individual lines of sight. We begin this survey with a sample of 40 high resolution (R~45000), high signal to noise ratio (S/N~70) quasar spectra at redshift 2.1<z<4.7, publicly available in the European Southern Observatory (ESO) archive. The extraordinary quality of this data set enables us to detect the proximity effect signature not only in the combined quasar sample, but also along each individual sight line. This allows us to determine not only the UV background intensity at the mean redshift of this sample, but also to estimate its intensity in small (Delta z~0.2) redshift intervals in the range 2<z<4. Our estimates (J_nu_0~ 3x10^{-22} erg s^{-1} cm^{-2} Hz^{-1} sr^{-1}) are for the first time in very good agreement with different constraints of its evolution obtained from theoretical predictions and numerical simulations. We continue this systematic analysis of the proximity effect with the largest search to date invoking the Sloan Digital Sky Survey (SDSS) data set. The sample consists of 1733 quasars at redshifts z>2.3. In spite of the low resolution and limited S/N we detect the proximity effect on about 98\% of the quasars at a high significance level. Thereby we are able to determine the evolution of the UV background photoionisation rate within the redshift range 2<z<5 finding Gamma_b~ 1.6x10^{-12} s^{-1}. With these new measurements we explore literature estimates of the quasar luminosity function and predict the stellar luminosity density up to redshift of about z~5. Our results are globally in good agreement with recent determinations inferred from deep surveys of high redshift galaxies. We then compare our measurements on the UV background photoionisation rate inferred from the two samples at high and low resolution. While these data sets show extreme differences, our determinations are in considerable agreement at z<3.3, even though they show less agreement at higher redshifts. We suspect that this may be caused by either the small number of high resolution quasar spectra at the highest redshifts considered or by some systematic effect due to the limited data quality of SDSS. Complementary to the observational investigation of the proximity effect on high redshift quasars, we exploit some theoretical aspects linked to and based on the results on this phenomenon. We employ complex numerical simulations of structure formation to achieve a better representation of the Ly-alpha forest. Modelling the signature of the proximity effect on randomly selected sight lines, we prove the advantages of dealing with individual lines of sight instead of combining their signal to investigate this phenomenon. Furthermore, we develop and test novel techniques aimed at a more precise determination of the proximity effect signal. With this investigation we demonstrate that the technique developed and employed in this thesis is the most accurate adopted thus far. Tighter determinations of the UV background are certainly based on suitable methods to detect its signature, but also on a deeper understanding of the environments in which quasars form and evolve. We initiate an investigation of complex numerical simulations including the radiative transport of energy to model in a more detailed way the proximity effect. Such a simulation may lead to the characterisation of the quasar environment based on the comparison between the observed and simulated statistical properties of the proximity effect signature.
With the rise of electronic integration between organizations, the need for a precise specification of interaction behavior increases. Information systems, replacing interaction previously carried out by humans via phone, faxes and emails, require a precise specification for handling all possible situations. Such interaction behavior is described in process choreographies. Choreographies enumerate the roles involved, the allowed interactions, the message contents and the behavioral dependencies between interactions. Choreographies serve as interaction contract and are the starting point for adapting existing business processes and systems or for implementing new software components. As a thorough analysis and comparison of choreography modeling languages is missing in the literature, this thesis introduces a requirements framework for choreography languages and uses it for comparing current choreography languages. Language proposals for overcoming the limitations are given for choreography modeling on the conceptual and on the technical level. Using an interconnection modeling style, behavioral dependencies are defined on a per-role basis and different roles are interconnected using message flow. This thesis reveals a number of modeling "anti-patterns" for interconnection modeling, motivating further investigations on choreography languages following the interaction modeling style. Here, interactions are seen as atomic building blocks and the behavioral dependencies between them are defined globally. Two novel language proposals are put forward for this modeling style which have already influenced industrial standardization initiatives. While avoiding many of the pitfalls of interconnection modeling, new anomalies can arise in interaction models. A choreography might not be realizable, i.e. there does not exist a set of interacting roles that collectively realize the specified behavior. This thesis investigates different dimensions of realizability.
Molecular photoswitches are attracting much attention lately mostly because of their possible applications in nano technology, and their role in biology. One of the widely studied representatives of photochromic molecules is azobenzene (AB). With light, by a static electric field, or with tunneling electrons this specie can be "switched" from the flat and energetically more stable trans form, into the compact cis form. The back reaction can be induced optically or thermally. Quantum chemical calculations, mostly based on density functional theory, on the AB molecule, AB derivatives and related systems are presented. All the calculations were done for isolated species, however, with implications for latest experimental results aiming at the switching of surface mounted ABs. In some of these experiments, it is assumed that the switching process is substrate mediated, by attaching an electron or a hole to the adsorbate forming short-lived anion or cation resonances. Therefore, we calculated also cationic and anionic ABs in this work. An influence of external electric fields on the potential energy surfaces, was also studied. Further, by the type, number and positioning of various substituent groups, systematic changes on activation energies and rates for the thermal cis-to-trans isomerization can be enforced. The nature of the transition state for ground state isomerization was investigated. Applying Eyring's transition state theory, trends in activation energies and rates were predicted and are, where a comparison was possible, in good agreement with experimental data. Further, thermal isomerization was studied in solution, for which a polarizable continuum model was employed. The influence of substitution and an environment leaves its traces on structural properties of molecules and quantitative appearance of calculated UV/Vis spectra, as well. Finally, an explicit treatment of a solid substrate was demonstrated for the conformational switching, by scanning tunneling microscope, of a 1,5-cyclooctadiene (COD) molecule at a Si(001) surface, treated by a cluster model. At first, we studied energetics and potential energy surfaces along relevant switching coordinates by quantum chemical calculations, followed by the switching dynamics using wave packet methods. We show that, in spite the simplicity of the model, our calculations support the switching of adsorbed COD, by inelastic electron tunneling at low temperatures.
Übergewicht und Adipositas führen zu Insulinresistenz und erhöhen deutlich das Risiko für die Entwicklung von Typ-2-Diabetes und kardiovaskulären Erkrankungen. Sowohl Adipositas als auch die Suszeptibilität gegenüber Diabetes sind zu einem erheblichen Teil genetisch determiniert. Die relevanten Risikogene, deren Interaktion mit der Umwelt, insbesondere mit Bestandteilen der Nahrung, und die Pathomechanismen, die zur Insulinresistenz und Diabetes führen, sind nicht vollständig aufgeklärt. In der vorliegenden Arbeit sollte durch Genexpressionsanalysen des weißen Fettgewebes (WAT) und der Langerhansschen Inseln die Entstehung und Progression von Adipositas und Typ-2-Diabetes untersucht werden, um relevante Pathomechanismen und neue Kandidatengene zu identifizieren. Zu diesem Zweck wurden Diät-Interventionsstudien mit NZO- und verwandten NZL-Mäusen, zwei polygenen Mausmodellen für das humane metabolische Syndrom, durchgeführt. Eine kohlenhydrathaltige Hochfett-Diät (HF: 14,6 % Fettanteil) führte in beiden Mausmodellen zu früher Adipositas, Insulinresistenz und Typ 2 Diabetes. Eine fettreduzierte Standarddiät (SD: 3,3 % Fettanteil), welche die Entstehung von Adipositas und Diabetes stark verzögert, sowie eine diabetesprotektive kohlenhydratfreie Hochfett-Diät (CHF: 30,2 % Fettanteil) dienten als Kontrolldiäten. Mit Hilfe der Microarray-Technologie wurden genomweite Expressionsprofile des WAT erstellt. Pankreatische Inseln wurden durch laserbasierte Mikropräparation (Laser Capture Microdissection; LCM) isoliert und ebenfalls hinsichtlich ihres Expressionsprofils analysiert. Differenziell exprimierte Gene wurden durch Real-Time-PCR validiert. Im WAT der NZO-Maus bewirkte die HF-Diät eine reduzierte Expression nukleärer Gene der oxidativen Phosphorylierung und von lipogenen Enzymen. Dies deutet auf eine inadäquate Fettspeicherung und -verwertung in diesen Tieren hin. Die Reduktion in der Fettspeicherung und -oxidation ist spezifisch für das adipöse NZO-Modell und konnte bei der schlanken SJL Maus nicht beobachtet werden, was auf eine mögliche Beteiligung an der Entstehung der Insulinresistenz hinweist. Zusätzlich wurde bestätigt, dass die Expansion des Fettgewebes bei der adipösen NZO-Maus eine zeitlich verzögerte Infiltration von Makrophagen in das WAT und dort eine lokale Immunantwort auslöst. Darüber hinaus wurde die Methode der LCM etabliert und zur Gewinnung hochangereicherter RNA aus den Langerhansschen Inseln eingesetzt. In erstmalig durchgeführten genomweiten Expressionsanalysen wurde zu einem frühen Zeitpunkt in der Diabetesentwicklung der Einfluss einer diabetogenen HF-Diät und einer diabetesprotektiven CHF-Diät auf das Expressionsprofil von pankreatischen Inselzellen verglichen. Im Gegensatz zum WAT bewirkt die diabetogene HF-Diät in Inselzellen einerseits, eine erhöhte Expression von nukleären Genen für die oxidative Phosphorylierung und andererseits von Genen, die mit Zellproliferation assoziiert sind. Zudem wurden 37 bereits annotierte Gene identifiziert, deren differenzielle Expression mit der Diabetesentwicklung korreliert. Das Peptidhormon Cholecystokinin (Cck, 11,8-fach erhöht durch die HF) stellt eines der am stärksten herauf regulierten Gene dar. Die hohe Anreicherung der Cck-mRNA in Inselzellen deutet auf eine bisher unbekannte Funktion des Hormons in der Regulation der Inselzellproliferation hin. Der Transkriptionsfaktor Mlxipl (ChREBP; 3,8-fach erniedrigt durch die HF) stellt in Langerhansschen Inseln eines der am stärksten herunter regulierten Gene dar. Ferner wurde ChREBP, dessen Funktion als glucoseregulierter Transkriptionsfaktor für lipogene Enzyme bislang in der Leber, aber nicht in Inselzellen nachgewiesen werden konnte, erstmals immunhistochemisch in Inselzellen detektiert. Dies deutet auf eine neue, bisher unbekannte regulatorische Funktion von ChREBP im Glucosesensor-Mechanismus der Inselzellen hin. Eine durchgeführte Korrelation der mit der Diabetesentwicklung assoziierten, differenziell exprimierten Inselzellgene mit Genvarianten aus humanen genomweiten Assoziationsstudien für Typ-2-Diabetes (WTCCC, Broad-DGI-T2D-Studie) ermöglichte die Identifizierung von 24 neuartigen Diabetes-Kandidatengenen. Die Ergebnisse der erstmals am polygenen NZO-Mausmodell durchgeführten genomweiten Expressionsuntersuchungen bestätigen bisherige Befunde aus Mausmodellen für Adipositas und Diabetes (z.B. ob/ob- und db/db-Mäuse), zeigen in einigen Fällen aber auch Unterschiede auf. Insbesondere in der oxidativen Phosphorylierung könnten die Ergebnisse relevant sein für das Verständnis der Pathogenese des polygen-bedingten humanen metabolischen Syndroms.
Das folgende Forschungsprojekt beschäftigt sich mit metakognitiven und motivationalen Fähigkeiten als Teilbereiche des selbstgesteuerten Lernens. Es untersucht den Nutzen und die Grenzen von Lerntagebüchern, die zugeschnitten wurden auf Grundschülerinnen und Grundschüler mit Migrationshintergrund. Das Ziel der Studie war es herauszufinden, ob und wie selbststeurungsbezogene Lernprozesse durch den Einsatz von Lerntagebüchern gemessen und verändert werden können. Hierzu führten 28 Grundschülerinnen und Grundschüler 14 Wochen lang während des Unterrichts ein halbstandardisiertes Lerntagebuch in Anlehnung an Wohland/Spinath (2004). Zur Messung von Veränderungen in metakognitiven und motivationalen Fähigkeiten füllten 43 Schülerinnen und Schüler zweier Experimentalgruppen und einer Kontrollgruppe vor und nach der Lerntagebuch-Intervention standardisierte Fragebögen aus. Weiterhin wurden die 28 Lerntagebücher der Experimentalgruppen inhalts- und prozessanalytisch ausgewertet. Außerdem wurden Interviews mit den Lehrkräften über ihre Unterrichtspraxis geführt und einige Schülerinnen und Schüler zu ihrer Wahrnehmung der Lerntagebucharbeit befragt. Die Ergebnisse der Analyse der Lerntagebuchdaten zeigen, dass die 28 Schülerinnen und Schüler mit Migrationshintergrund erfolgreich ihren Lernprozess bei der Bearbeitung einer Aufgabe verbalisierten. Sie haben weiterhin erfolgreich Vorhersagen über ihre Vorgehensweisen zur Lösung einer Aufgabe getroffen. Die Lerntagebücher unterstützten sie darin, ihre metakognitiven Erfahrungen (Efklides/Petkaki 2005) zu kalibrieren (Desoete/Roeyers 2006). Den Lernenden ist es gelungen, ihre Repräsentationen über das Lösen einer Aufgabe aufeinander (fein-) abzustimmen, während sie daran arbeiteten. Mit Hilfe von Zeitreihenanalysen konnte gezeigt werden, dass die Schülerinnen und Schüler die Fragen im Lerntagebuch gegen Ende der Intervention oberflächlicher beantworteten und die Lerntagebücher tendenziell weniger häufig ausgefüllt wurden (negative Trends). Eine Erklärung für die geringere Antworthäufigkeit, die zu negativen Verlaufskurven über die Zeit führten, könnte sein, dass die Instruktionsdichte durch den Mix an offenen und geschlossenen Fragen im Lerntagebuch zu hoch war. Die Lernenden haben sich möglicherweise so an die Fragen bzw. Antwortformate gewöhnt, dass die Motivation, in das Lerntagebuch zu schreiben, geringer wurde.
Dietary antioxidants are believed to play an important role in the prevention and treatment of a variety of diseases associated with oxidative stress. Although there is a wide range of dietary antioxidants, the bulk of the research to date has been focused on the nutrient antioxidants vitamin C, E, and carotenoids. Certain relatively uncommon antioxidants such as lipoic acid (LA), and phenolic compounds such as (-)-epicatechin (EC), (-)-epigallocatechin (EGC), (-)-epicatechin gallate (ECG), and (-)-epigallocatechin gallate (EGCG), have not been extensively investigated although they may exert greater antioxidant potency than that of carotenoids and vitamins. Extracts from selected plants and plant byproducts may represent rich sources for one or more of such antioxidants and therefore exhibit higher effects than a single antioxidant due to the synergistic effects produced between such antioxidants. However, in the last decade a number of epidemiological, animal and in vitro studies have suggested a protective and therapeutic potency of these antioxidants in a broad range of diseases such as cancer, diabetes, atherosclerosis, cataract and acute and chronic neurological disorders. Inflammation, the response of the host toward any infection or injury, plays a central role in the development of many chronic diseases. Several evidences demonstrated the rise of different types of cancer from sites of inflammation. This suggests that active oxygen species and some cytokines generated in the inflamed tissues can cause injury to DNA and ultimately lead to carcinogenesis. Diethylnitrosamine (DEN) is one of the most important environmental carcinogens, present in a variety of foods, alcoholic beverages, tobacco smoke and it can be synthesized endogenously. In addition to the liver it can induce carcinogenesis in other organs like kidney, trachea, lung, esophagus, fore stomach, and nasal cavity. Several epidemiological and laboratory studies indicate that nitroso compounds including DEN may induce hyperplasia and chronic inflammation which is closely associated with the development of hepatocellular carcinoma. Despite increasing evidence on the potential of antioxidants in modulating the etiology of chronic diseases, little is known about their role in inflammation and acute phase response (APR). Therefore the aim of the present work was to study the protective effect of water and solvent extracts of eight plant and plant byproducts including green tea, artichoke, spinach, broccoli, onion and eggplant, orange and potato peels as well as eight antioxidants agents including EC, EGC, ECG, EGCG, ascorbic acid (AA), acetylcysteine (NAC), α-LA, and alpha-tocopherol (α-TOC) toward acute inflammation induced by interleukin-6 (IL-6) and hepatotoxicity induced by DEN in vitro. The negative acute phase proteins (APP), transthyretin (TTR) and retinol-binding protein (RBP) were used as inflammatory biomarkers analyzed by ELISA, whereas neutral red assay was used for evaluating the cytotoxicity. All experiments were performed in vitro using human hepatocarcinoma cell line (HepG2). Additionally the antioxidant activity was measured by TEAC and FRAP assays, phenolic content was measured by Folin–Ciocalteu and characterized by HPLC. Moreover, the microheterogeneity of TTR was detected using immunoprecipitation assay combined with SELDI-TOF MS. Results of present study showed that HepG2 cells provide a simple, sensitive in vitro system for studying the regulation of the negative APP, TTR and RBP under free and inflammatory condition. IL-6, a potent proinflammatory cytokine, in a concentration of 25 ng/ml was able to reduce TTR and RBP secretion by approximately 50-60% after 24h of incubation. With exception of broccoli and water extract of onion which showed pro-inflammatory effects in this study, all other plant extracts, at specific concentrations, were able to elevate TTR secretion in normal condition and even under treatment of IL-6 where the effect was quite lower. Green tea followed by artichoke and potato peel exhibited the highest elevation in TTR concentration which reached 1.1 and 2.5 folds of control in presence and absences of IL-6 respectively. In general Plant extracts were ordered according their anti-inflammatory potency as following: in water extracts; green tea > artichoke > potato peel > orange peel > spinach > eggplant peel, where in solvent extracts; green tea > artichoke > potato peel > spinach > eggplant peel > onion > orange peel. The antiinflammatory effect of water extracts of green tea, artichoke and orange peel were significantly higher than their corresponding solvent extracts whereas water extracts of eggplant-, potato peels and spinach showed lower effect than their solvent extracts. On the other hand α-LA followed by EGCG and ECG exhibited the highest elevation in TTR concentration compared to other antioxidants. The relation between the anti-inflammatory potential and antioxidants activity and phenolic content for the investigated substances was generally weak. This may suggest the involvement of other mechanisms than antioxidants properties for the observed effect. TTR secreted by HepG2 cells has a molecular structure quite similar to the purified standard and serum TTR in which all the three main variants are contained including native, S-cystinylated and Sglutathionylated TTR. Interestingly, a variant with molecular mass of 13453.8 + 8.3 Da has been detected only in TTR secreted by HepG2. Among all investigated antioxidants and plant extracts, six substances were able to elevate the native preferable TTR variant. The potency of these substances can be ordered as following α-LA > NAC > onion > AA > EGCG > green tea. A weak correlation between elevation on TTR and shifting to the native form was observed. Similar weak correlation has also been observed between antioxidants activity and elevation in native TTR. Although DEN was able to induce cell death in a concentration dependent manner, it requires considerably higher concentrations for its effects especially after 24h. This may be attributed to a lack in cytochrome P450 enzymes produced by HepG2. At selected concentrations some antioxidants and plant extracts significantly attenuate DEN cytotoxicity as following: spinach > α-LA > artichoke > orange peel > eggplant peel > α-TOC > onion > AA. Contrary all other substances especially green tea, broccoli, potato peel, and ECG stimulate DEN toxicity. In conclusion, this study demonstrated that selected antioxidants and plant extracts may attenuate the inflammatory process, not only by their antioxidants potency but also by other mechanisms which remain unclear. They may also play a vital role on stabilizing the tetramic structure of TTR and thereby prevent amyloidosis diseases. Lipoic acid represents in this study unique function against inflammation and hepatotoxicity. Despite the protective effect demonstrated by investigated substances, attention should also be given to the pro-oxidant and potential cytotoxic effects produced at higher concentrations.
Despite general concern that the massive deposits of methane stored under permafrost underground and undersea could be released into the atmosphere due to rising temperatures attributed to global climate change, little is known about the methanogenic microorganisms in permafrost sediments, their role in methane emissions, and their phylogeny. The aim of this thesis was to increase knowledge of uncultivated methanogenic microorganisms in submarine and terrestrial permafrost deposits, their community composition, the role they play with regard to methane emissions, and their phylogeny. It is assumed that methanogenic communities in warmer submarine permafrost may serve as a model to anticipate the response of methanogenic communities in colder terrestrial permafrost to rising temperatures. The compositions of methanogenic communities were examined in terrestrial and submarine permafrost sediment samples. The submarine permafrost studied in this research was 10°C warmer than the terrestrial permafrost. By polymerase chain reaction (PCR), DNA was extracted from each of the samples and analyzed by molecular microbiological methods such as PCR-DGGE, RT-PCR, and cloning. Furthermore, these samples were used for in vitro experiment and FISH. The submarine permafrost analysis of the isotope composition of CH4 suggested a relationship between methane content and in situ active methanogenesis. Furthermore, active methanogenesis was proven using 13C-isotope measurements of methane in submarine permafrost sediment with a high TOC value and a high methane concentration. In the molecular-microbiological studies uncultivated lines of Methanosarcina, Methanomicrobiales, Methanobacteriacea and the Groups 1.3 and Marine Benthic from Crenarchaeota were found in all submarine and terrestrial permafrost samples. Methanosarcina was the dominant group of the Archaea in all submarine and terrestrial permafrost samples. The archaeal community composition, in particular, the methanogenic community composition showed diversity with changes in temperatures. Furthermore, cell count of methanogens in submarine permafrost was 10 times higher than in terrestrial permafrost. In vitro experiments showed that methanogens adapt quickly and well to higher temperatures. If temperatures rise due to climate change, an increase in methanogenic activity can be expected as long as organic material is sufficiently available and qualitatively adequate.
Water shortage is a serious threat for many societies worldwide. In drylands, water management measures like the construction of reservoirs are affected by eroded sediments transported in the rivers. Thus, the capability of assessing water and sediment fluxes at the river basin scale is of vital importance to support management decisions and policy making. This subject was addressed by the DFG-funded SESAM-project (Sediment Export from large Semi-Arid catchments: Measurements and Modelling). As a part of this project, this thesis focuses on (1) the development and implementation of an erosion module for a meso-scale catchment model, (2) the development of upscaling and generalization methods for the parameterization of such model, (3) the execution of measurements to obtain data required for the modelling and (4) the application of the model to different study areas and its evaluation. The research was carried out in two meso-scale dryland catchments in NE-Spain: Ribera Salada (200 km²) and Isábena (450 km²). Adressing objective 1, WASA-SED, a spatially semi-distributed model for water and sediment transport at the meso-scale was developed. The model simulates runoff and erosion processes at the hillslope scale, transport processes of suspended and bedload fluxes in the river reaches, and retention and remobilisation processes of sediments in reservoirs. This thesis introduces the model concept, presents current model applications and discusses its capabilities and limitations. Modelling at larger scales faces the dilemma of describing relevant processes while maintaining a manageable demand for input data and computation time. WASA-SED addresses this challenge by employing an innovative catena-based upscaling approach: the landscape is represented by characteristic toposequences. For deriving these toposequences with regard to multiple attributes (eg. topography, soils, vegetation) the LUMP-algorithm (Landscape Unit Mapping Program) was developed and related to objective 2. It incorporates an algorithm to retrieve representative catenas and their attributes, based on a Digital Elevation Model and supplemental spatial data. These catenas are classified to provide the discretization for the WASA-SED model. For objective 3, water and sediment fluxes were monitored at the catchment outlet of the Isábena and some of its sub-catchments. For sediment yield estimation, the intermittent measurements of suspended sediment concentration (SSC) had to be interpolated. This thesis presents a comparison of traditional sediment rating curves (SRCs), generalized linear models (GLMs) and non-parametric regression using Random Forests (RF) and Quantile Regression Forests (QRF). The observed SSCs are highly variable and range over six orders of magnitude. For these data, traditional SRCs performed poorly, as did GLMs, despite including other relevant process variables (e.g. rainfall intensities, discharge characteristics). RF and QRF proved to be very robust and performed favourably for reproducing sediment dynamics. QRF additionally excels in providing estimates on the accuracy of the predictions. Subsequent analysis showed that most of the sediment was exported during intense storms of late summer. Later floods yielded successively less sediment. Comparing sediment generation to yield at the outlet suggested considerable storage effects within the river channel. Addressing objective 4, the WASA-SED model was parameterized for the two study areas in NE Spain and applied with different foci. For Ribera Salada, the uncalibrated model yielded reasonable results for runoff and sediment. It provided quantitative measures of the change in runoff and sediment yield for different land-uses. Additional land management scenarios were presented and compared to impacts caused by climate change projections. In contrast, the application for the Isábena focussed on exploring the full potential of the model's predictive capabilities. The calibrated model achieved an acceptable performance for the validation period in terms of water and sediment fluxes. The inadequate representation of the lower sub-catchments inflicted considerable reductions on model performance, while results for the headwater catchments showed good agreement despite stark contrasts in sediment yield. In summary, the application of WASA-SED to three catchments proved the model framework to be a practicable multi-scale approach. It successfully links the hillslope to the catchment scale and integrates the three components hillslope, river and reservoir in one model. Thus, it provides a feasible approach for tackling issues of water and sediment yield at the meso-scale. The crucial role of processes like transmission losses and sediment storage in the river has been identified. Further advances can be expected when the representation of connectivity of water and sediment fluxes (intra-hillslope, hillslope-river, intra-river) is refined and input data improves.
The fat-soluble vitamin A, which is chemically referred to retinol (ROH), is known to be essential for the process of vision, the immune system but also for cell differentiation and proliferation. Recently, ROH itself has been reported to be involved in adipogenesis and a ROH transport protein, the retinol-binding protein 4 (RBP4), in insulin resistance and type 2 diabetes. However, there is still considerable scientific debate about this relation. With the increasing amount of studies investigating the relation of ROH in obesity and type 2 diabetes, basic research is an essential prerequisite for interpreting these results. This thesis enhances the knowledge on this relation by reviewing ROH metabolism on extra- and intracellular level. Aim 1: In the blood stream ROH is transported in a complex with RBP4 and a second protein, transthyretin (TTR), to the target cells. The levels of RBP4 and TTR are influenced by several factors but mainly by liver and kidney function. The reason for that is that liver and the kidneys are the sites of RBP4 synthesis and catabolism, respectively. Interestingly, obesity and type 2 diabetes involve disorders of the liver and the kidneys. Therefore the aim was to investigate factors that influence RBP4 and TTR levels in relation to obesity and type 2 diabetes (Part 1). Aim 2: Once arrived in the target cell ROH is bound to cellular retinol-binding protein type I (CRBP-I) and metabolised: ROH can either be stored as retinylesters or it can be oxidised to retinoic acid (RA). By acting as a transcription factor in the nucleus RA may influence processes such as adipogenesis. Therefore vitamin A has been postulated to be involved in obesity and type 2 diabetes. CRBP-I is known to mediate the storage of ROH in the liver, but the extra-hepatic metabolism and the functions of CRBP-I are not well known. This has been investigated in Part 2 of this work. Material & Methods: RBP4 and TTR levels were investigated by ELISA in serum samples of human subjects with overweight, type 2 diabetes, kidney or liver dysfunction. Molecular alterations of the RBP4 and TTR protein structure were analysed by MALDI-TOF mass spectrometry. The functions of intracellular CRBP-I were investigated in CRBP-I knock-out mice in liver and extra-hepatic tissues by measuring ROH levels as well as the levels of its storage form, the retinylesters, using reverse phase HPLC. The postprandial uptake of ROH into tissues was analysed using labelled ROH. The mRNA levels of enzymes that metabolize ROH were examined by real-time polymerase chain reaction (RCR). Results: The previous published results showing increased RBP4 levels in type 2 diabetic patients could not be confirmed in this work. However, it could be shown that during kidney dysfunction RBP4 levels are increased and that RBP4 and TTR levels are decreased during liver dysfunction. The important new finding of this work is that increased RBP4 levels in type 2 diabetic mice were increased when kidney function was decreased. Thus an increase in RBP4 levels in type 2 diabetes may be the effect of a reduced kidney function which is common in type 2 diabetes. Interestingly, during severe kidney dysfunction the molecular structure of RBP4 and TTR was altered in a specific manner which was not the case during liver diseases and type 2 diabetes. This underlines the important function of the kidneys in RBP4 metabolism. CRBP-I has been confirmed to be responsible for the ROH storage in the liver since CRBP-I knock-out mice had decreased ROH and retinylesters (the storage form of ROH) levels in the liver. Interestingly, in the adipose tissue (the second largest ROH storage tissue in the body) ROH and retinylesters levels were higher in the CRBP-I knock-out compared to the wild-type mice. It could be shown in this work that a different ROH binding protein, cellular retinol-binding protein type III, is upregulated in CRBP-I knock-out mice. Moreover enzymes were identified which mediate very efficiently ROH esterification in the adipose tissue of the knock-out mice. In the pancreas there was a higher postprandial ROH uptake in the CRBP-I knock-out compard to wild-type mice. Even under a vitamin A deficient diet the knock-out animals had ROH and retinylesters levels which were comparable to wild-type animals. These results underline the important role of ROH for insulin secretion in the pancreas. Summing up, there is evidence that RBP4 levels are more determined by kidney function than by type 2 diabetes and that specific molecular modifications occur during kidney dysfunction. The results in adipose tissue and pancreas of CRBP-I knock-out mice support the hypothesis that ROH plays an important role in glucose and lipid metabolism.
Parataxe et subordination, ces deux termes, parfois antithétiques, sont problématiques du fait même de leur extrême polysémie. C’est de cette ambiguïté que naît l’objet d’étude, les constructions asyndétiques, au statut incertain entre intégration et indépendance. Dans cette thèse, nous proposons de réinterroger ce phénomène ancien et déjà bien connu en ancien français, en le mettant en regard des remises en question et avancées des recherches actuelles sur le sujet. Pour cela, il nous faut tout d'abord poser une définition de ce qu'est la subordination. Nous montrons ensuite que les constructions asyndétiques sont bien des cas de subordination. Cette thèse établit enfin que ce phénomène constitue, en ancien français du moins, une variante libre en syntaxe. Sa répartition et sa présence dans les textes a cependant très tôt diminué, mais l’existence de phénomènes parallèles en français moderne, tout comme d’autres indices, nous permettent de faire l’hypothèse que cette évolution tient d’une alternance oral / écrit. Cette thèse montre ainsi que les problèmes, comme les enjeux, ne diffèrent finalement pas, quel que soit l’état de langue et que la parataxe constitue bien une construction dans le système de la langue.
Der Streifenkiwi (Apteryx mantelli) kommt im Freiland nur auf der Nordinsel Neuseelands vor. Aufgrund des gefährdeten Bestands ist eine sich selbst erhaltene Zoopopulation wichtig. Kenntnisse des Verhaltens helfen, die Ansprüche der Tiere zu verstehen. Zudem können sie darüber Auskunft geben, inwiefern das Wohlbefinden eines Tieres gegeben ist. Durch die Untersuchung der Brutaktivität sollte ein Überblick über den allgemeinen Verlauf der Brut gegeben und Aktivitätsmuster für den Berliner Hahn erarbeitet werden, um den Verlauf zukünftiger Bruten einschätzen und eventuell positiv beeinflussen zu können. Dazu kamen die Untersuchung der täglichen Aktivität einer Henne sowie Beobachtungen des Verhaltens der Tiere. Diese dienten der Bestandsaufnahme der gezeigten Verhaltensweisen und sollten zusammen mit der Aktivität die Grundlage zur Einschätzung bilden, ob die Ansprüche der Kiwis im Zoo Berlin erfüllt werden, und Hinweise zur Verbesserung der Haltung geben. Die Brutaktivität des Hahnes konnte über drei Brutperioden hinweg detailliert dargestellt werden und zeigte, dass nicht nur innerhalb der Art sondern bei einem einzigen Tier unter ähnlichen Bedingungen die Variabilität so groß sein kann, dass sie für Vorhersagen über den Erfolg einer Brut nicht geeignet ist. Im Zusammenhang mit der Aktivität der Henne ließen sich keine Auffälligkeiten erkennen, die auf eine allgemeine Störung der Tiere schließen lassen oder für eine Beeinträchtigung der Brut verantwortlich gemacht werden könnten. Soweit aus den Beobachtungen im Freiland geschlossen werden kann, scheinen die Kiwis im Zoo ein weitgehend natürliches Verhalten zu zeigen. Die Haltungsbedingungen scheinen den Ansprüchen der Tiere zu entsprechen. Es ließen sich nur bedingt Strategien entwickeln, um die Bedingungen für die Brut und damit für die Nachzucht zu verbessern, da sich die Aktivität des Hahnes während der Brut von Jahr zu Jahr als unerwartet variabel erwies. Für ein weiteres Verständnis des Brutverhaltens und eine mögliche Verbesserung der Bedingungen wäre eine Untersuchung zum Einfluss verschiedener Umweltfaktoren auf die Brutaktivität des Hahnes wünschenswert.
This work presents mathematical and computational approaches to cover various aspects of metabolic network modelling, especially regarding the limited availability of detailed kinetic knowledge on reaction rates. It is shown that precise mathematical formulations of problems are needed i) to find appropriate and, if possible, efficient algorithms to solve them, and ii) to determine the quality of the found approximate solutions. Furthermore, some means are introduced to gain insights on dynamic properties of metabolic networks either directly from the network structure or by additionally incorporating steady-state information. Finally, an approach to identify key reactions in a metabolic networks is introduced, which helps to develop simple yet useful kinetic models. The rise of novel techniques renders genome sequencing increasingly fast and cheap. In the near future, this will allow to analyze biological networks not only for species but also for individuals. Hence, automatic reconstruction of metabolic networks provides itself as a means for evaluating this huge amount of experimental data. A mathematical formulation as an optimization problem is presented, taking into account existing knowledge and experimental data as well as the probabilistic predictions of various bioinformatical methods. The reconstructed networks are optimized for having large connected components of high accuracy, hence avoiding fragmentation into small isolated subnetworks. The usefulness of this formalism is exemplified on the reconstruction of the sucrose biosynthesis pathway in Chlamydomonas reinhardtii. The problem is shown to be computationally demanding and therefore necessitates efficient approximation algorithms. The problem of minimal nutrient requirements for genome-scale metabolic networks is analyzed. Given a metabolic network and a set of target metabolites, the inverse scope problem has as it objective determining a minimal set of metabolites that have to be provided in order to produce the target metabolites. These target metabolites might stem from experimental measurements and therefore are known to be produced by the metabolic network under study, or are given as the desired end-products of a biotechological application. The inverse scope problem is shown to be computationally hard to solve. However, I assume that the complexity strongly depends on the number of directed cycles within the metabolic network. This might guide the development of efficient approximation algorithms. Assuming mass-action kinetics, chemical reaction network theory (CRNT) allows for eliciting conclusions about multistability directly from the structure of metabolic networks. Although CRNT is based on mass-action kinetics originally, it is shown how to incorporate further reaction schemes by emulating molecular enzyme mechanisms. CRNT is used to compare several models of the Calvin cycle, which differ in size and level of abstraction. Definite results are obtained for small models, but the available set of theorems and algorithms provided by CRNT can not be applied to larger models due to the computational limitations of the currently available implementations of the provided algorithms. Given the stoichiometry of a metabolic network together with steady-state fluxes and concentrations, structural kinetic modelling allows to analyze the dynamic behavior of the metabolic network, even if the explicit rate equations are not known. In particular, this sampling approach is used to study the stabilizing effects of allosteric regulation in a model of human erythrocytes. Furthermore, the reactions of that model can be ranked according to their impact on stability of the steady state. The most important reactions in that respect are identified as hexokinase, phosphofructokinase and pyruvate kinase, which are known to be highly regulated and almost irreversible. Kinetic modelling approaches using standard rate equations are compared and evaluated against reference models for erythrocytes and hepatocytes. The results from this simplified kinetic models can simulate acceptably the temporal behavior for small changes around a given steady state, but fail to capture important characteristics for larger changes. The aforementioned approach to rank reactions according to their influence on stability is used to identify a small number of key reactions. These reactions are modelled in detail, including knowledge about allosteric regulation, while all other reactions were still described by simplified reaction rates. These so-called hybrid models can capture the characteristics of the reference models significantly better than the simplified models alone. The resulting hybrid models might serve as a good starting point for kinetic modelling of genome-scale metabolic networks, as they provide reasonable results in the absence of experimental data, regarding, for instance, allosteric regulations, for a vast majority of enzymatic reactions.
Leaves are the main photosynthetic organs of vascular plants, and leaf development is dependent on a proper control of gene expression. Transcription factors (TFs) are global regulators of gene expression that play essential roles in almost all biological processes among eukaryotes. This PhD project focused on the characterization of the sink-to-source transition of Arabidopsis leaves and on the analysis of TFs that play a role in early leaf development. The sink-to-source transition occurs when the young emerging leaves (net carbon importers) acquire a positive photosynthetic balance and start exporting photoassimilates. We have established molecular and physiological markers (i.e., CAB1 and CAB2 expression levels, AtSUC2 and AtCHoR expression patterns, chlorophyll and starch levels, and photosynthetic electron transport rates) to identify the starting point of the transition, especially because the sink-to-source is not accompanied by a visual phenotype in contrast to other developmental transitions, such as the mature-to-senescent transition of leaves. The sink-to-source transition can be divided into two different processes: one light dependent, related to photosynthesis and light responses; and one light independent or impaired, related to the changes in the vascular tissue that occur when leaves change from an import to an export mode. Furthermore, starch, but not sucrose, has been identified as one of the potential signalling molecules for this transition. The expression level of 1880 TFs during early leaf development was assessed by qRTPCR, and 153 TFs were found to exhibit differential expression levels of at least 5-fold. GRF, MYB and SRS are TF families, which are overrepresented among the differentially expressed TFs. Additionally, processes like cell identity acquisition, formation of the epidermis and leaf development are overrepresented among the differentially expressed TFs, which helps to validate the results obtained. Two of these TFs were further characterized. bZIP21 is a gene up-regulated during the sink-to-source and mature-to-senescent transitions. Its expression pattern in leaves overlaps with the one observed for AtCHoR, therefore it constitutes a good marker for the sink-to-source transition. Homozygous null mutants of bZIP21 could not be obtained, indicating that the total absence of bZIP21 function may be lethal to the plant. Phylogenetic analyses indicate that bZIP21 is an orthologue of Liguleless2 from maize. In these analyses, we identified that the whole set of bZIPs in plants originated from four founder genes, and that all bZIPs from angiosperms can be classified into 13 groups of homologues and 34 Possible Groups of Orthologues (PoGOs). bHLH64 is a gene highly expressed in early sink leaves, its expression is downregulated during the mature-to-senescent transition. Null mutants of bHLH64 are characterized by delayed bolting when compared to the wild-type; this indicates a possible delay in the sink-to-source transition or the retention of a juvenile identity. A third TF, Dof4, was also characterized. Dof4 is neither differentially expressed during the sink-to-source nor during the senescent-to-mature transition, but a null mutant of Dof4 develops bigger leaves than the wild-type and forms a greater number of siliques. The Dof4 null mutant has proven to be a good background for biomass accumulation analysis. Though not overrepresented during the sink-to-source transition, NAC transcription factors seem to contribute significantly to the mature-to-senescent transition. Twenty two NACs from Arabidopsis and 44 from rice are differentially expressed during late stages of leaf development. Phylogenetic analyses revealed that most of these NACs cluster into three big groups of homologues, indicating functional conservation between eudicots and monocots. To prove functional conservation of orthologues, the expression of ten NAC genes of barley was analysed. Eight of the ten NAC genes were found to be differentially expressed during senescence. The use of evolutionary approaches combined with functional studies is thus expected to support the transfer of current knowledge of gene control gained in model species to crops.
Hohe Leistungsansprüche im Wettkampfsport erfordern von den Athleten eine hohe sportliche Belastbarkeit. Möglichkeiten die Trainingsumfänge und -intensitäten zu erhöhen, sind z.T. ausgeschöpft. So bestehen nach wie vor Bestrebungen neue Wege zu finden, um mögliche Leistungsreserven zu erschließen. Elektrotherapieverfahren haben sich im klinischen Alltag, u.a. zur Behandlung von Traumata, bewährt und werden häufig zum Zweck der Analgesierung, Verbesserung der Gewebedurchblutung und zur Muskelstimulation angewandt. Deren Einsatz im adjuvanten Bereich der Trainingsbegleitung wurde bislang nur vereinzelt beschrieben. In der vorliegenden Studie wurden die Auswirkungen einer elektromagnetischen Anwendungsform auf ausgewählte psycho-physische Parameter untersucht (Kontrollgruppenvergleich mit placebokontrolliertem Design), um Aussagen über praxisrelevante Ansätze zur trainingsunterstützenden Betreuung abzuleiten. Es stellte sich die Frage, ob eine Intervention (15 x / 4 Wo.) mit frequenzmodulierten Wechselströmen im vorwiegend niederfrequenten Wirkungsspektrum (0-10000Hz, 5 μA / cm², CellVAS®) zu einer Beeinflussung der untersuchten Parameter führen und dahingehend nachhaltige leistungsfördernde oder -reduzierende Effekte erzielt werden könnten. Des Weiteren sollte geprüft werden, inwiefen die erhobenen Parameter (PWC170, Squat-Jump, Lateralflexion der Wirbelsäule und SF36®) aussagekräftig genug sind. Die Wirksamkeit des Applikationsform wurde im Prä-Post-Vergleich vor (T1), nach (T2) und 4 Wo. nach Abschluss (T3, Nachhaltigkeit) der Intervention analysiert. Die Teilnehmer der Kontrollgruppe erhielten vergleichbare Applikationen im Placebomodus. Das Probandenkollektiv bestand aus gesunden Leistungssportlern, deren Sportarten einen hohen Kraftausdaueranteil enthielten (n=127). Die Gruppenzuteilung erfolgte teilrandomisiert in Haupt- (HG) und Kontrollgruppe (KG). Zudem wurden die Gruppen zusätzlich geschlechtsspezifisch getrennt. Im Untersuchungsverlauf ließen sich Veränderungen für die Leistungsparameter PWC170 und Squat Jump erkennen. Inwiefern diese Abweichungen auf den Einfluss der Intervention mit frequenzmodulierten Wechselströmen im niederfrequenten Wirkungsspektrum zurückzuführen sind, konnte in dieser Untersuchung nicht eindeutig geklärt werden. Die nachgewiesenen Effekte ließen sich nach den zu Grunde liegenden wissenschaftlichen Standards nicht statistisch valide belegen. Der wissenschaftliche Nachweis einer mögliche Leistungsveränderung konnte nicht abschließend erbracht werden. Im therapeutischen Bereich hat die untersuchte Applikationsform, auf Basis der bestehen Studienlage, ihre Anwendung gefunden und kann bedenkenlos verwendet werden. Für den Einsatz als unterstützendes Verfahren in der sportlichen Praxis besteht nach wie vor Bedarf an validen, randomisierten Studien, die die Wirksamkeit der Applikationsform auf psycho-physische Parameter von Athleten nachhaltig belegen, bevor sie in der sportlichen Praxis Anwendung finden sollten.
Trying to do two things at once decreases performance of one or both tasks in many cases compared to the situation when one performs each task by itself. The present thesis deals with the question why and in which cases these dual-task costs emerge and moreover, whether there are cases in which people are able to process two cognitive tasks at the same time without costs. In four experiments the influence of stimulus-response (S-R) compatibility, S-R modality pairings, interindividual differences, and practice on parallel processing ability of two tasks are examined. Results show that parallel processing is possible. Nevertheless, dual-task costs emerge when: the personal processing strategy is serial, the two tasks have not been practiced together, S-R compatibility of both tasks is low (e.g. when a left target has to be responded with a right key press and in the other task an auditorily presented “A” has to be responded by saying “B”), and modality pairings of both tasks are Non Standard (i.e., visual-spatial stimuli are responded vocally whereas auditory-verbal stimuli are responded manually). Results are explained with respect to executive-based (S-R compatibility) and content-based crosstalk (S-R modality pairings) between tasks. Finally, an alternative information processing account with respect to the central stage of response selection (i.e., the translation of the stimulus to the response) is presented.
Die Kombination von Polymeren mit Peptiden vereint die Eigenschaften beider Stoffklassen miteinander. Dabei können die strukturbildenden Eigenschaften der Peptide genutzt werden, um Polymere zu organisieren. In der vorliegenden Arbeit wurde ein Polymer-Peptid-Konjugat verwendet, das sich in Wasser zu Bändern anordnet. Die treibende Kraft für diesen Prozess ist die Anordnung des Peptidteils zu β-Faltblattstrukturen. Das Polymer-Peptid-Aggregat besitzt einen Peptidkern mit funktionalen Oberflächen, der lateral von einer Polyethylenoxidschale umgeben ist. Durch Änderung der Peptidsequenz war es bisher möglich, die Eigenschaften dieser Fasern zu variieren. In der Arbeit wird ein modularer Ansatz zur vielfältigen Modifizierung einer Polymer-Peptid-Faser entwickelt. So ist es möglich, die Eigenschaften der Fasern einzustellen, ohne die strukturbildende β-Faltblattsequenz verändern zu müssen. Um weitere Funktionen an den Fasern anzubringen, wurde die 1,3-dipolaren Addition verwendet. Diese Reaktion beschreibt die konzertierte Umlagerung eines Azides mit einem Alkin. Sie ist in den meisten Lösungsmitteln unter hohen Ausbeuten durchführbar. Im Rahmen der Arbeit wird die Erzeugung von Aziden untersucht und auf die Polymer-Peptid-Fasern übertragen. Der Diazotransfer stellte dabei die Methode der Wahl dar, so können Azidgruppen aus Aminen gewonnen werden. Unter Verwendung der 1,3-dipolaren Addition konnten verschiedene alkinfunktionale Moleküle kovalent an die azidfunktionalisierten Polymer-Peptid-Fasern gebunden werden. So wurde ein Fluoreszenzfarbstoff an die Fasern gebunden, der eine Abbildung der Fasern mittels konfokaler Mikroskopie erlaubte. Weiterhin wurden die Eigenschaften der Fasern durch Addition dreier carboxylfunktionaler Moleküle modifiziert. Diese Fasern konnten weiter genutzt werden, um Kalzium zu binden. Dabei variierte die Anzahl der gebundenen Kalziumionen in Abhängigkeit der jeweiligen Fasermodifikation erheblich. Weitere Untersuchungen, die Morphologie von Kalziumcarbonatkristallen betreffend, werden aktuell durchgeführt. Die kovalente Anbringung eines reduzierenden Zuckers an die Polymer-Peptid-Fasern erlaubt die Abscheidung von Silber aus Tollens Reagenz. Durch eine Entwicklung analog zur Schwarz-Weiss-Photographie können in nachfolgenden Arbeiten so Silberdrähte in Nanogröße erzeugt werden. An die azidfunktionalen Fasern können weitere funktionale Moleküle angebracht werden, um die Eigenschaften und das Anwendungsspektrum der Polymer-Peptid-Fasern zu erweitern.
The seismicity of the Dead Sea fault zone (DSFZ) during the last two millennia is characterized by a number of damaging and partly devastating earthquakes. These events pose a considerable seismic hazard and seismic risk to Syria, Lebanon, Palestine, Jordan, and Israel. The occurrence rates for large earthquakes along the DSFZ show indications to temporal changes in the long-term view. The aim of this thesis is to find out, if the occurrence rates of large earthquakes (Mw ≥ 6) in different parts of the DSFZ are time-dependent and how. The results are applied to probabilistic seismic hazard assessments (PSHA) in the DSFZ and neighboring areas. Therefore, four time-dependent statistical models (distributions), including Weibull, Gamma, Lognormal and Brownian Passage Time (BPT), are applied beside the exponential distribution (Poisson process) as the classical time-independent model. In order to make sure, if the earthquake occurrence rate follows a unimodal or a multimodal form, a nonparametric bootstrap test of multimodality has been done. A modified method of weighted Maximum Likelihood Estimation (MLE) is applied to estimate the parameters of the models. For the multimodal cases, an Expectation Maximization (EM) method is used in addition to the MLE method. The selection of the best model is done by two methods; the Bayesian Information Criterion (BIC) as well as a modified Kolmogorov-Smirnov goodness-of-fit test. Finally, the confidence intervals of the estimated parameters corresponding to the candidate models are calculated, using the bootstrap confidence sets. In this thesis, earthquakes with Mw ≥ 6 along the DSFZ, with a width of about 20 km and inside 29.5° ≤ latitude ≤ 37° are considered as the dataset. The completeness of this dataset is calculated since 300 A.D. The DSFZ has been divided into three sub zones; the southern, the central and the northern sub zone respectively. The central and the northern sub zones have been investigated but not the southern sub zone, because of the lack of sufficient data. The results of the thesis for the central part of the DSFZ show that the earthquake occurrence rate does not significantly pursue a multimodal form. There is also no considerable difference between the time-dependent and time-independent models. Since the time-independent model is easier to interpret, the earthquake occurrence rate in this sub zone has been estimated under the exponential distribution assumption (Poisson process) and will be considered as time-independent with the amount of 9.72 * 10-3 events/year. The northern part of the DSFZ is a special case, where the last earthquake has occurred in 1872 (about 137 years ago). However, the mean recurrence time of Mw ≥ 6 events in this area is about 51 years. Moreover, about 96 percent of the observed earthquake inter-event times (the time between two successive earthquakes) in the dataset regarding to this sub zone are smaller than 137 years. Therefore, it is a zone with an overdue earthquake. The results for this sub zone verify that the earthquake occurrence rate is strongly time-dependent, especially shortly after an earthquake occurrence. A bimodal Weibull-Weibull model has been selected as the best fit for this sub zone. The earthquake occurrence rate, corresponding to the selected model, is a smooth function of time and reveals two clusters within the time after an earthquake occurrence. The first cluster begins right after an earthquake occurrence, lasts about 80 years, and is explicitly time-dependent. The occurrence rate, regarding to this cluster, is considerably lower right after an earthquake occurrence, increases strongly during the following ten years and reaches its maximum about 0.024 events/year, then decreases over the next 70 years to its minimum about 0.0145 events/year. The second cluster begins 80 years after an earthquake occurrence and lasts until the next earthquake occurs. The earthquake occurrence rate, corresponding to this cluster, increases extremely slowly, such as it can be considered as an almost constant rate about 0.015 events/year. The results are applied to calculate the time-dependent PSHA in the northern part of the DSFZ and neighbouring areas.
Although the basic structure of biological membranes is provided by the lipid bilayer, most of the specific functions are carried out by membrane proteins (MPs) such as channels, ion-pumps and receptors. Additionally, it is known, that mutations in MPs are directly or indirectly involved in many diseases. Thus, structure determination of MPs is of major interest not only in structural biology but also in pharmacology, especially for drug development. Advances in structural biology of membrane proteins (MPs) have been strongly supported by the success of three leading techniques: X-ray crystallography, electron microscopy and solution NMR spectroscopy. However, X-ray crystallography and electron microscopy, require highly diffracting 3D or 2D crystals, respectively. Today, structure determination of non-crystalline solid protein preparations has been made possible through rapid progress of solid-state MAS NMR methodology for biological systems. Castellani et. al. solved and refined the first structure of a microcrystalline protein using only solid-state MAS NMR spectroscopy. These successful application open up perspectives to access systems that are difficult to crystallise or that form large heterogeneous complexes and insoluble aggregates, for example ligands bound to a MP-receptor, protein fibrils and heterogeneous proteins aggregates. Solid-state MAS NMR spectroscopy is in principle well suited to study MP at atomic resolution. In this thesis, different types of MP preparations were tested for their suitability to be studied by solid-state MAS NMR. Proteoliposomes, poorly diffracting 2D crystals and a PEG precipitate of the outer membrane protein G (OmpG) were prepared as a model system for large MPs. Results from this work, combined with data found in the literature, show that highly diffracting crystalline material is not a prerequirement for structural analysis of MPs by solid-state MAS NMR. Instead, it is possible to use non-diffracting 3D crystals, MP precipitates, poorly diffracting 2D crystals and proteoliposomes. For the latter two types of preparations, the MP is reconstituted into a lipid bilayer, which thus allows the structural investigation in a quasi-native environment. In addition, to prepare a MP sample for solid-state MAS NMR it is possible to use screening methods, that are well established for 3D and 2D crystallisation of MPs. Hopefully, these findings will open a fourth method for structural investigation of MP. The prerequisite for structural studies by NMR in general, and the most time consuming step, is always the assignment of resonances to specific nuclei within the protein. Since the last few years an ever-increasing number of assignments from solid-state MAS NMR of uniformly carbon and nitrogen labelled samples is being reported, mostly for small proteins of up to around 150 amino acids in length. However, the complexity of the spectra increases with increasing molecular weight of the protein. Thus the conventional assignment strategies developed for small proteins do not yield a sufficiently high degree of assignment for the large MP OmpG (281 amino acids). Therefore, a new assignment strategy to find starting points for large MPs was devised. The assignment procedure is based on a sample with [2,3-13C, 15N]-labelled Tyr and Phe and uniformly labelled alanine and glycine. This labelling pattern reduces the spectral overlap as well as the number of assignment possibilities. In order to extend the assignment, four other specifically labelled OmpG samples were used. The assignment procedure starts with the identification of the spin systems of each labelled amino acid using 2D 13C-13C and 3D NCACX correlation experiments. In a second step, 2D and 3D NCOCX type experiments are used for the sequential assignment of the observed resonances to specific nuclei in the OmpG amino acid sequence. Additionally, it was shown in this work, that biosynthetically site directed labelled samples, which are normally used to observe long-range correlations, were helpful to confirm the assignment. Another approach to find assignment starting points in large protein systems, is the use of spectroscopic filtering techniques. A filtering block that selects methyl resonances was used to find further assignment starting points for OmpG. Combining all these techniques, it was possible to assign nearly 50 % of the observed signals to the OmpG sequence. Using this information, a prediction of the secondary structure elements of OmpG was possible. Most of the calculated motifs were in good aggreement with the crystal structures of OmpG. The approaches presented here should be applicable to a wide variety of MPs and MP-complexes and should thus open a new avenue for the structural biology of MPs.
Dispersal behavior plays an important role for the geographical distribution and population structure of any given species. Individual’s fitness, reproductive and competitive ability, and dispersal behavior can be determined by the age of the individual. Age-dependent as well as density-dependent dispersal patterns are common in many bird species. In this thesis, I first present age-dependent breeding ability and natal site fidelity in white storks (Ciconia ciconia); migratory birds breeding in large parts of Europe. I predicted that both the proportion of breeding birds and natal site fidelity increase with the age. After the seventies of the last century, following a steep population decline, a recovery of the white stork population has been observed in many regions in Europe. Increasing population density in the white stork population in Eastern Germany especially after 1983 allowed examining density- as well as age-dependent breeding dispersal patterns. Therefore second, I present whether: young birds show more often and longer breeding dispersal than old birds, and frequency of dispersal events increase with the population density increase, especially in the young storks. Third, I present age- and density-dependent dispersal direction preferences in the give population. I asked whether and how the major spring migration direction interacts with dispersal directions of white storks: in different age, and under different population densities. The proportion of breeding individuals increased in the first 22 years of life and then decreased suggesting, the senescent decay in aging storks. Young storks were more faithful to their natal sites than old storks probably due to their innate migratory direction and distance. Young storks dispersed more frequently than old storks in general, but not for longer distance. Proportion of dispersing individuals increased significantly with increasing population densities indicating, density- dependent dispersal behavior in white storks. Moreover, the finding of a significant interaction effects between the age of dispersing birds and year (1980–2006) suggesting, older birds dispersed more from their previous nest sites over time due to increased competition. Both young and old storks dispersed along their spring migration direction; however, directional preferences were different in young storks and old storks. Young storks tended to settle down before reaching their previous nest sites (leading to the south-eastward dispersal) while old birds tended to keep migrating along the migration direction after reaching their previous nest sites (leading to the north-westward dispersal). Cues triggering dispersal events may be age-dependent. Changes in the dispersal direction over time were observed. Dispersal direction became obscured during the second half of the observation period (1993–2006). Increase in competition may affect dispersal behavior in storks. I discuss the potential role of: age for the observed age-dependent dispersal behavior, and competition for the density dependent dispersal behavior. This Ph.D. thesis contributes significantly to the understanding of population structure and geographical distribution of white storks. Moreover, presented age- and density (competition)-dependent dispersal behavior helps understanding underpinning mechanisms of dispersal behavior in bird species.
A huge number of applications require coherent radiation in the visible spectral range. Since diode lasers are very compact and efficient light sources, there exists a great interest to cover these applications with diode laser emission. Despite modern band gap engineering not all wavelengths can be accessed with diode laser radiation. Especially in the visible spectral range between 480 nm and 630 nm no emission from diode lasers is available, yet. Nonlinear frequency conversion of near-infrared radiation is a common way to generate coherent emission in the visible spectral range. However, radiation with extraordinary spatial temporal and spectral quality is required to pump frequency conversion. Broad area (BA) diode lasers are reliable high power light sources in the near-infrared spectral range. They belong to the most efficient coherent light sources with electro-optical efficiencies of more than 70%. Standard BA lasers are not suitable as pump lasers for frequency conversion because of their poor beam quality and spectral properties. For this purpose, tapered lasers and diode lasers with Bragg gratings are utilized. However, these new diode laser structures demand for additional manufacturing and assembling steps that makes their processing challenging and expensive. An alternative to BA diode lasers is the stripe-array architecture. The emitting area of a stripe-array diode laser is comparable to a BA device and the manufacturing of these arrays requires only one additional process step. Such a stripe-array consists of several narrow striped emitters realized with close proximity. Due to the overlap of the fields of neighboring emitters or the presence of leaky waves, a strong coupling between the emitters exists. As a consequence, the emission of such an array is characterized by a so called supermode. However, for the free running stripe-array mode competition between several supermodes occurs because of the lack of wavelength stabilization. This leads to power fluctuations, spectral instabilities and poor beam quality. Thus, it was necessary to study the emission properties of those stripe-arrays to find new concepts to realize an external synchronization of the emitters. The aim was to achieve stable longitudinal and transversal single mode operation with high output powers giving a brightness sufficient for efficient nonlinear frequency conversion. For this purpose a comprehensive analysis of the stripe-array devices was done here. The physical effects that are the origin of the emission characteristics were investigated theoretically and experimentally. In this context numerical models could be verified and extended. A good agreement between simulation and experiment was observed. One way to stabilize a specific supermode of an array is to operate it in an external cavity. Based on mathematical simulations and experimental work, it was possible to design novel external cavities to select a specific supermode and stabilize all emitters of the array at the same wavelength. This resulted in stable emission with 1 W output power, a narrow bandwidth in the range of 2 MHz and a very good beam quality with M²<1.5. This is a new level of brightness and brilliance compared to other BA and stripe-array diode laser systems. The emission from this external cavity diode laser (ECDL) satisfied the requirements for nonlinear frequency conversion. Furthermore, a huge improvement to existing concepts was made. In the next step newly available periodically poled crystals were used for second harmonic generation (SHG) in single pass setups. With the stripe-array ECDL as pump source, more than 140 mW of coherent radiation at 488 nm could be generated with a very high opto-optical conversion efficiency. The generated blue light had very good transversal and longitudinal properties and could be used to generate biphotons by parametric down-conversion. This was feasible because of the improvement made with the infrared stripe-array diode lasers due to the development of new physical concepts.
1. Problemstellung und Relevanz des Themas Die deutsche Hochschullandschaft hat in den letzten Jahren zahlreiche Veränderungen bewältigen müssen und steht weiterhin großen Herausforderungen gegenüber, durch welche sich zunehmend wettbewerbsähnliche Merkmale in diesem Sektor verfestigen: • Umstellung auf international vergleichbare Studiengänge • Neuregelung der Studienplatzvergabe • Einführung von Studiengebühren in einigen Bundesländern • Leistungsindikatoren zur Verteilung der staatlichen Haushaltsmittel • Demographischer Wandel Eine Bildungseinrichtung besitzt mehrere Anspruchsgruppen: die Studierenden, welche Bildungsleistungen nachfragen, den Staat, der für die Leistungen zahlt, die Öffentlichkeit, die an Grundlagenforschungen interessiert ist und schließlich die Wirtschaft, die Absolventen rekrutiert (vgl. Berthold, C. 2001, S.431). Die Hochschulen befinden sich untereinander verstärkt im Wettbewerb um qualifizierte (und ggf. zahlungswillige) Studierende, um finanzielle Mittel vom Staat oder aus der Privatwirtschaft und um renommierte Wissenschaftler. Hochschulen müssen sich nun den veränderten Bedingungen anpassen, um auch weiterhin im nationalen und internationalen Wettbewerb überlebensfähig zu bleiben. Grundsätzlich kann sich hierbei an in der Privatwirtschaft erfolgreich eingesetzten Marketinginstrumenten orientiert werden. 2. Zielsetzung und Aufbau der Arbeit Nach einer Analyse der oben genannten Rahmenbedingungen, wird im ersten Teil dieser Arbeit gezeigt, welche Erkenntnisse aus dem Marketing auf Hochschulen übertragen werden können. Dabei werden sowohl strategische Fragen beleuchtet als auch die Instrumente des Marketing-Mix vorgestellt. In einer anschließenden Untersuchung wurden Faktoren bestimmt, welche sich positiv auf den Entwicklungsstand von Marketingaktivitäten an Hochschulen auswirken. Dabei konnten - beispielhaft für die Region Berlin/Brandenburg - sechs verschiedene Hochschultypen identifiziert werden. Diese weisen, in Abhängigkeit der verschiedenen Eigenschaften der jeweiligen Institutionen, einen unterschiedlichen Entwicklungsstand oder ein anderes Verständnis von Hochschulmarketing auf. Aufgrund dessen erscheinen für sie jeweils andere Marketingstrategien empfehlenswert. Die größte Rolle für den differenzierten Status quo im Hochschulmarketing an Berliner und Brandenburger Hochschulen spielt die Stärke des äußeren Drucks unter dem sich die Hochschule befindet, um ihre Auslastung und die notwendige finanzielle Ausstattung sicherzustellen. Ferner unterscheiden sich die Hochschulleitungen erheblich in ihrem Engagement und der Bereitschaft, diesen Herausforderungen mit Marketinginstrumenten zu begegnen. Trotz der gestiegenen Anzahl von Beiträgen zur Notwendigkeit der Einführung von ökonomischen Überlegungen auch im Hochschulmanagement gibt es viele Kritiker, die ein Ende der Freiheit für Forschung und Lehre prophezeien, wenn der Marketing-Gedanke verstärkt auch an Bildungseinrichtungen Einzug hält. Unumstritten ist, dass Managementansätze aus der privaten Wirtschaft nicht ohne weiteres auf eine Hochschule adaptiert werden können. Wahrscheinlich besteht jedoch die größere Gefahr für Freiheit und Erfolg von Forschung und Lehre in der Missachtung dieser aktuellen Tendenzen (vgl. Tutt 2006, S. 171)!
Analytical ultracentrifugation (AUC) has made an important contribution to polymer and particle characterization since its invention by Svedberg (Svedberg and Nichols 1923; Svedberg and Pederson 1940) in 1923. In 1926, Svedberg won the Nobel price for his scientific work on disperse systems including work with AUC. The first important discovery performed with AUC was to show the existence of macromolecules. Since that time AUC has become an important tool to study polymers in biophysics and biochemistry. AUC is an absolute technique that does not need any standard. Molar masses between 200 and 1014 g/mol and particle size between 1 and 5000 nm can be detected by AUC. Sample can be fractionated into its components due to its molar mass, particle size, structure or density without any stationary phase requirement as it is the case in chromatographic techniques. This very property of AUC earns it an important status in the analysis of polymers and particles. The distribution of molar mass, particle sizes and densities can be measured with the fractionation. Different types of experiments can give complementary physicochemical parameters. For example, sedimentation equilibrium experiments can lead to the study of pure thermodynamics. For complex mixtures, AUC is the main method that can analyze the system. Interactions between molecules can be studied at different concentrations without destroying the chemical equilibrium (Kim et al. 1977). Biologically relevant weak interactions can also be monitored (K ≈ 10-100 M-1). An analytical ultracentrifuge experiment can yield the following information: • Molecular weight of the sample • Number of the components in the sample if the sample is not a single component • Homogeneity of the sample • Molecular weight distribution if the sample is not a single component • Size and shape of macromolecules & particles • Aggregation & interaction of macromolecules • Conformational changes of macromolecules • Sedimentation coefficient and density distribution Such an extremely wide application area of AUC allows the investigation of all samples consisting of a solvent and a dispersed or dissolved substance including gels, micro gels, dispersions, emulsions and solutions. Another fact is that solvent or pH limitation does not exist for this method. A lot of new application areas are still flourishing, although the technique is 80 years old. In 1970s, 1500 AUC were operational throughout the world. At those times, due to the limitation in detection technologies, experimental results were obtained with photographic records. As time passed, faster techniques such as size exclusion chromatography (SEC), light scattering (LS) or SDS-gel electrophoresis occupied the same research fields with AUC. Due to these relatively new techniques, AUC began to loose its importance. In the 1980s, only a few AUC were in use throughout the world. In the beginning of the 1990s a modern AUC -the Optima XL-A - was released by Beckman Instruments (Giebeler 1992). The Optima XL-A was equipped with a modern computerized scanning absorption detector. The addition of Rayleigh Interference Optics is introduced which is called XL-I AUC. Furthermore, major development in computers made the analysis easier with the help of new analysis software. Today, about 400 XL-I AUC exist worldwide. It is usually applied in the industry of pharmacy, biopharmacy and polymer companies as well as in academic research fields such as biochemistry, biophysics, molecular biology and material science. About 350 core scientific publications which use analytical ultracentrifugation are published every year (source: SciFinder 2008 ) with an increasing number of references (436 reference in 2008). A tremendous progress has been made in method and analysis software after digitalization of experimental data with the release of XL-I. In comparison to the previous decade, data analysis became more efficient and reliable. Today, AUC labs can routinely use sophisticated data analysis methods for determination of sedimentation coefficient distributions (Demeler and van Holde 2004; Schuck 2000; Stafford 1992), molar mass distributions (Brookes and Demeler 2008; Brookes et al. 2006; Brown and Schuck 2006), interaction constants (Cao and Demeler 2008; Schuck 1998; Stafford and Sherwood 2004), particle size distributions with Angstrom resolution (Cölfen and Pauck 1997) and the simulations determination of size and shape distributions from sedimentation velocity experiments (Brookes and Demeler 2005; Brookes et al. 2006). These methods are also available in powerful software packages that combines various methods, such as, Ultrascan (Demeler 2005), Sedift/Sedphat (Schuck 1998; Vistica et al. 2004) and Sedanal (Stafford and Sherwood 2004). All these powerful packages are free of charge. Furthermore, Ultrascans source code is licensed under the GNU Public License (http://www.gnu.org/copyleft/gpl.html). Thus, Ultrascan can be further improved by any research group. Workshops are organized to support these software packages. Despite of the tremendous developments in data analysis, hardware for the system has not developed much. Although there are various user developed detectors in research laboratories, they are not commercially available. Since 1992, only one new optical system called “the fluorescence optics” (Schmidt and Reisner, 1992, MacGregor et al. 2004, MacGregor, 2006, Laue and Kroe, in press) has been commercialized. However, except that, there has been no commercially available improvement in the optical system. The interesting fact about the current hardware of the XL-I is that it is 20 years old, although there has been an enormous development in microelectronics, software and in optical systems in the last 20 years, which could be utilized for improved detectors. As examples of user developed detector, Bhattacharyya (Bhattacharyya 2006) described a Multiwavelength-Analytical Ultracentrifuge (MWL-AUC), a Raman detector and a small angle laser light scattering detector in his PhD thesis. MWL-AUC became operational, but a very high noise level prevented to work with real samples. Tests with the Raman detector were not successful due to the low light intensity and thus high integration time is required. The small angle laser light scattering detector could only detect latex particles but failed to detect smaller particles and molecules due to low sensitivity of the detector (a photodiode was used as detector). The primary motivation of this work is to construct a detector which can measure new physico-chemical properties with AUC with a nicely fractionated sample in the cell. The final goal is to obtain a multiwavelength detector for the AUC that measures complementary quantities. Instrument development is an option for a scientist only when there is a huge potential benefit but there is no available commercial enterprise developing appropriate equipment, or if there is not enough financial support to buy it. The first case was our motivation for developing detectors for AUC. Our aim is to use today’s technological advances in microelectronics, programming, mechanics in order to develop new detectors for AUC and improve the existing MWL detector to routine operation mode. The project has multiple aspects which can be listed as mechanical, electronical, optical, software, hardware, chemical, industrial and biological. Hence, by its nature it is a multidisciplinary project. Again by its nature it contains the structural problem of its kind; the problem of determining the exact discipline to follow at each new step. It comprises the risk of becoming lost in some direction. Having that fact in mind, we have chosen the simplest possible solution to any optical, mechanical, electronic, software or hardware problem we have encountered and we have always tried to see the overall picture. In this research, we have designed CCD-C-AUC (CCD Camera UV/Vis absorption detector for AUC) and SLS-AUC (Static Light Scattering detector for AUC) and tested them. One of the SLS-AUC designs produced successful test results, but the design could not be brought to the operational stage. However, the operational state Multiwavelength Analytical Ultracentrifuge (MWL-AUC) AUC has been developed which is an important detector in the fields of chemistry, biology and industry. In this thesis, the operational state Multiwavelength Analytical Ultracentrifuge (MWL-AUC) AUC is to be introduced. Consequently, three different applications of MWL-AUC to the aforementioned disciplines shall be presented. First of all, application of MWL-AUC to a biological system which is a mixture of proteins lgG, aldolase and BSA is presented. An application of MWL-AUC to a mass-produced industrial sample (β-carotene gelatin composite particles) which is manufactured by BASF AG, is presented. Finally, it is shown how MWL-AUC will impact on nano-particle science by investigating the quantum size effect of CdTe and its growth mechanism. In this thesis, mainly the relation between new technological developments and detector development for AUC is investigated. Pioneering results are obtained that indicate the possible direction to be followed for the future of AUC. As an example, each MWL-AUC data contains thousands of wavelengths. MWL-AUC data also contains spectral information at each radial point. Data can be separated to its single wavelength files and can be analyzed classically with existing software packages. All the existing software packages including Ultrascan, Sedfit, Sedanal can analyze only single wavelength data, so new extraordinary software developments are needed. As a first attempt, Emre Brookes and Borries Demeler have developed mutliwavelength module in order to analyze the MWL-AUC data. This module analyzes each wavelength separately and independently. We appreciate Emre Brookes and Borries Demeler for their important contribution to the development of the software. Unfortunately, this module requires huge amount of computer power and does not take into account the spectral information during the analysis. New software algorithms are needed which take into account the spectral information and analyze all wavelengths accordingly. We would like also invite the programmers of Ultrascan, Sedfit, Sedanal and the other programs, to develop new algorithms in this direction.
For the elucidation of the dynamics of signal transduction processes that are induced by cellular interactions, defined events along the signal transduction cascade and subsequent activation steps have to be analyzed and then also correlated with each other. This cannot be achieved by ensemble measurements because averaging biological data ignores the variability in timing and response patterns of individual cells and leads to highly blurred results. Instead, only a multi-parameter analysis at a single-cell level is able to exploit the information that is crucially needed for deducing the signaling pathways involved. The aim of this work was to develop a process line that allows the initiation of cell-cell or cell-particle interactions while at the same time the induced cellular reactions can be analyzed at various stages along the signal transduction cascade and correlated with each other. As this approach requires the gentle management of individually addressable cells, a dielectrophoresis (DEP)-based microfluidic system was employed that provides the manipulation of microscale objects with very high spatiotemporal precision and without the need of contacting the cell membrane. The system offers a high potential for automation and parallelization. This is essential for achieving a high level of robustness and reproducibility, which are key requirements in order to qualify this approach for a biomedical application. As an example process for intercellular communication, T cell activation has been chosen. The activation of the single T cells was triggered by contacting them individually with microbeads that were coated with antibodies directed against specific cell surface proteins, like the T cell receptor-associated kinase CD3 and the costimulatory molecule CD28 (CD; cluster of differentiation). The stimulation of the cells with the functionalized beads led to a rapid rise of their cytosolic Ca2+ concentration which was analyzed by a dual-wavelength ratiometric fluorescence measurement of the Ca2+-sensitive dye Fura-2. After Ca2+ imaging, the cells were isolated individually from the microfluidic system and cultivated further. Cell division and expression of the marker molecule CD69 as a late activation event of great significance were analyzed the following day and correlated with the previously recorded Ca2+ traces for each individual cell. It turned out such that the temporal profile of the Ca2+ traces between both activated and non-activated cells as well as dividing and non-dividing cells differed significantly. This shows that the pattern of Ca2+ signals in T cells can provide early information about a later reaction of the cell. As isolated cells are highly delicate objects, a precondition for these experiments was the successful adaptation of the system to maintain the vitality of single cells during and after manipulation. In this context, the influences of the microfluidic environment as well as the applied electric fields on the vitality of the cells and the cytosolic Ca2+ concentration as crucially important physiological parameters were thoroughly investigated. While a short-term DEP manipulation did not affect the vitality of the cells, they showed irregular Ca2+ transients upon exposure to the DEP field only. The rate and the strength of these Ca2+ signals depended on exposure time, electric field strength and field frequency. By minimizing their occurrence rate, experimental conditions were identified that caused the least interference with the physiology of the cell. The possibility to precisely control the exact time point of stimulus application, to simultaneously analyze short-term reactions and to correlate them with later events of the signal transduction cascade on the level of individual cells makes this approach unique among previously described applications and offers new possibilities to unravel the mechanisms underlying intercellular communication.
About 2,000 of the more than 27,000 genes of the genetic model plant Arabidopsis thaliana encode for transcription factors (TFs), proteins that bind DNA in the promoter region of their target genes and thus act as transcriptional activators and repressors. Since TFs play essential roles in nearly all biological processes, they are of great scientific and biotechnological interest. This thesis concentrated on the functional characterisation of four selected members of the Arabidopsis DOF-family, namely DOF1.2, DOF3.1, DOF3.5 and DOF5.2, which were selected because of their specific expression pattern in the root tip, a region that comprises the stem cell niche and cells for the perception of environmental stimuli. DOF1.2, DOF3.1 and DOF3.5 are previously uncharacterized members of the Arabidopsis DOF-family, while DOF5.2 has been shown to be involved in the phototrophic flowering response. However, its role in root development has not been described so far. To identify biological processes regulated by the four DOF proteins in detail, molecular and physiological characterization of transgenic plants with modified levels of DOF1.2, DOF3.1, DOF3.5 and DOF5.2 expression (constitutive and inducible over-expression, artificial microRNA) was performed. Additionally expression patterns of the TFs and their target genes were analyzed using promoter-GUS lines and publicly available microarray data. Finally putative protein-protein interaction partners and upstream regulating TFs were identified using the yeast two-hybrid and one-hybrid system. This combinatorial approach revealed distinct biological functions of DOF1.2, DOF3.1, DOF3.5 and DOF5.2 in the context of root development. DOF1.2 and DOF3.5 are specifically and exclusively expressed in the root cap, including the central root cap (columella) and the lateral root cap, organs which are essential to direct oriented root growth. It could be demonstrated that both genes work in the plant hormone auxin signaling pathway and have an impact on distal cell differentiation. Altered levels of gene expression lead to changes in auxin distribution, abnormal cell division patterns and altered root growth orientation. DOF3.1 and DOF5.2 share a specific expression pattern in the organizing centre of the root stem cell niche, called the quiescent centre. Both genes redundantly control cell differentiation in the root´s proximal meristem and unravel a novel transcriptional regulation pathway for genes enriched in the QC cells. Furthermore this work revealed a novel bipartite nuclear localisation signal being present in the protein sequence of the DOF TF family from all sequenced plant species. Summing up, this work provides an important input into our knowledge about the role of DOF TFs during root development. Future work will concentrate on revealing the exact regulatory networks of DOF1.2, DOF3.1, DOF3.5 and DOF5.2 and their possible biotechnological applications.
This thesis presents investigations on sediments from two African lakes which have been recording changes in their surrounding environmental and climate conditions since more than 200,000 years. Focus of this work is the time of the last Glacial and the Holocene (the last ~100,000 years before present [in the following 100 kyr BP]). One important precondition for this kind of research is a good understanding of the present ecosystems in and around the lakes and of the sediment formation under modern climate conditions. Both studies therefore include investigations on the modern environment (including organisms, soils, rocks, lake water and sediments). A 90 m long sediment sequence was investigated from Lake Tswaing (north-eastern South Africa) using geochemical analyses. These investigations document alternating periods of high detrital input and low (especially autochthonous) organic matter content and periods of low detrital input, carbonatic or evaporitic sedimentation and high autochthonous organic matter content. These alternations are interpreted as changes between relatively humid and arid conditions, respectively. Before c. 75 kyr BP, they seem to follow changes in local insolation whereas afterwards they appear to be acyclic and are probably caused by changes in ocean circulation and/or in the mean position of the Inter-Tropical Convergence Zone (ITCZ). Today, these factors have main influence on precipitation in this area where rainfall occurs almost exclusively during austral summer. All modern organisms were analysed for their biomarker and bulk organic and compound-specific stable carbon isotope composition. The same investigations on sediments from the modern lake floor document the mixed input of the investigated individual organisms and reveal additional influences by methanotrophic bacteria. A comparison of modern sediment characteristics with those of sediments covering the time 14 to 2 kyr BP shows changes in the productivity of the lake and the surrounding vegetation which are best explained by changes in hydrology. More humid conditions are indicated for times older than 10 kyr BP and younger than 7.5 kyr BP, whereas arid conditions prevailed in between. These observations agree with the results from sediment composition and indications from other climate archives nearby. The second lake study deals with Lake Challa, a small, deep crater lake on the foot of Mount Kilimanjaro. In this lake form mm-scale laminated sediments which were analyses with micro-XRF scanning for changes in the element composition. By comparing these results with investigations on thin sections, results from ongoing sediment trap studies, meteorological data, and investigations on the surrounding rocks and soils, I develop a model for seasonal variability in the limnology and sedimentation of Lake Challa. The lake appears to be stratified during the warm rain seasons (October – December and March – May) during which detrital material is delivered to the lake and carbonates precipitate. On the lake floor forms a dark lamina with high contents of Fe and Ti and high Ca/Al and low Mn/Fe ratios. Diatoms bloom during the cool and windy season (June – September) when mixing down to c. 60 m depth provides easily bio-available nutrients. Contemporaneously, Fe and Mn-oxides are precipitating which cause high Mn/Fe ratios in the light diatom-rich laminae of the sediments. Trends in the Mn/Fe ratio of the sediments are interpreted to reflect changes in the intensity or duration of seasonal mixing in Lake Challa. This interpretation is supported by parallel changes in the organic matter and biogenic silica content observed in the 22 m long profile recovered from Lake Challa. This covers the time of the last 25 kyr BP. It documents a transition around 16 kyr BP from relatively well-mixed conditions with high detrital input during glacial times to stronger stratified conditions which are probably related to increasing lake levels in Challa and generally more humid conditions in East Africa. Intensified mixing is recorded for the time of the Younger Dryas and the period between 11.4 and 10.7 kyr BP. For these periods, reduced intensity of the SW monsoon and intensified NE monsoon are reported from archives of the Indian-Asian Monsoon region, arguing for the latter as a probable source for wind mixing in Lake Challa. This connection is probably also responsible for contemporaneous events in the Mn/Fe ratios of the Lake Challa sediments and in other records of northern hemisphere monsoon intensity during the Holocene and underlines the close interaction of global low latitude atmospheric circulation.
Die Etablierung eines gesunden Ernährungsverhaltens unserer Kinder ist die wichtigste Voraussetzung für ihre körperliche, kognitive und emotionale Entwicklung. Dabei sind neben einer genetischen Disposition und kulturellen Gegebenheiten vor allem die Einflüsse der jeweiligen Betreuungspersonen ausschlaggebend. Die Eltern steuern sowohl direkt (durch Aufforderungen, Verbote u.ä.) als auch indirekt (durch die Förderung eigenverantwortlicher Entscheidungen u.ä.) das Ernährungsverhalten ihres Kindes. Untersuchungen zum mütterlichen Steuerungsverhalten konzentrierten sich bisher vorwiegend auf die Betrachtung direkter Strategien sowie auf altershomogene und sozial besser gestellte Gruppen. Aufgrund möglicher Verzerrungen durch die Betrachtung einzelner Ausschnitte des Zusammenhangs zwischen Steuerung und Ernährung wurde in der vorliegenden Arbeit ein Gesamtmodell spezifiziert, welches den Zusammenhang zwischen elterlicher Steuerung und kindlicher Ernährung unter Berücksichtigung von Sozial- und Gewichtsfaktoren abbildet. Dazu wurden drei Erhebungen mit insgesamt über 900 Müttern 1 – 10-jähriger Kinder durchgeführt. Innerhalb dieser Untersuchungen ist es gelungen, erstmalig ein deutschsprachiges Instrument zur Messung elterlicher Steuerungsstrategien in der Essenssituation (ISS) zu entwickeln. Die Analysen zeigten, dass bisher nur selten untersuchte Strategien, wie das explizite Bemühen um Vorbildwirkung und das Erlauben von eigenverantwortlichen Entscheidungen des Kindes, von den Müttern häufig angewandt werden. Die Analyse des komplexen Wirkungsgefüge von Steuerung, kindlicher Ernährung sowie sozialer und gewichtsbezogener Faktoren zeigte weiterhin, dass neben stabilen Faktoren, wie dem mütterlichen Status und dem Alter des Kindes, ein entscheidender Anteil der mütterlichen Steuerungsstrategien für die kindliche Ernährung verantwortlich ist. Die berichteten Ergebnisse zeigen auf, wie relevant die gemeinsame Betrachtung von gesunden und problematischen Nahrungsmitteln sowie die den Zusammenhang zwischen Steuerung und Ernährung beeinflussenden Faktoren innerhalb eines Modells ist. Zusammengefasst scheint vor allem die Steuerung durch Belohnung von und mit bestimmten Nahrungsmitteln eine für das kindliche Ernährungsverhalten und das Übergewichtsrisiko besonders kritische Strategie zu sein. Dies ist umso bedeutender, als bisherige Untersuchungen dieses Verhalten häufig in restriktive Strategien integriert betrachteten. Die separate Analyse wies jedoch darauf hin, dass vor allem die belohnenden Verhaltensanteile relevant sind. Dies zeigt, dass es für die Entwicklung einer gesunden kindlichen Ernährung tatsächlich veränderbare Verhaltensweisen gibt, die Eltern in Präventionsprogrammen oder anderen mit Kursen zum kindlichen Wohl assoziierten Einrichtungen vermittelt werden können.
Die Zielsetzung der vorliegenden Arbeit ist die Beschreibung hydrophober Bodeneigenschaften und deren Auswirkungen auf Oberflächenabfluss und Erosion auf verschiedenen Skalen. Die dazu durchgeführten Untersuchungen fanden auf einer Rekultivierungsfläche im Braunkohlegebiet Welzow Süd (Südostdeutschland) statt. Die Prozesse wurden auf drei Skalen untersucht, die von der Plotskala (1m²) über die Hangskala (300m²) bis zur Betrachtung eines kleinen Einzugsgebietes (4ha) reichen. Der Grad der hydrophoben Bodeneigenschaften wurde sowohl direkt, über die Bestimmung des Kontaktwinkel, als auch indirekt, über die Bestimmung der Persistenz, ermittelt. Dabei zeigte sich, dass der Boden im Winterhalbjahr hydrophil reagierte, während er im Sommerhalbjahr hydrophobe Bodeneigenschaften aufwies. Die Ergebnisse deuten darauf hin, dass ansteigende Bodenwassergehalte, die in der Literatur häufig als Ursache für einen Wechsel der Bodeneigenschaften angegeben werden, auf dieser Fläche nicht zu einem Umbruch der Bodenbedingungen führen. Stattdessen kam es als Folge des Auftauens von gefrorenem Boden zu hydrophilen Bodeneigenschaften, die zu einem Anstieg des Bodenwassergehalts führten. Räumliche Unterschiede zeigten sich in den geomorphologischen Einheiten. Rinnen und Rillen wiesen seltener hydrophobe Eigenschaften als die Zwischenrillenbereiche und Kuppen auf. Diese räumlichen und zeitlichen Variabilitäten wirkten sich auch auf den Oberflächenabfluss aus, der als Abflussbeiwert (ABW: Quotient aus Abfluss und Niederschlag) untersucht wurde. Der ABW liegt auf Böden mit hydrophoben Bodeneigenschaften (ABW=0,8) deutlich höher als bei jenen mit hydrophilen Eigenschaften(ABW=0,2), wie sie im Winter oder auf anderem Substrat vorzufinden sind (diese Werte beziehen sich auf die Plotskala). Betrachtet man die Auswirkungen auf unterschiedlichen Skalen, nimmt der Abflussbeiwert mit zunehmender Flächengröße ab (ABW = 0,8 auf der Plotskala, ABW = 0,5 auf der Hangskala und ABW = 0,2 im gesamten Gebiet), was in den hydrophil reagierenden Rillen und Rinnen auf der Hangskala und dem hydrophilen Substrat im Einzugsgebiet begründet ist. Zur Messung der Erosion wurden verschiedene, zum Teil neu entwickelte Methoden eingesetzt, um eine hohe zeitliche und räumliche Auflösung zu erreichen. Bei einer neu entwickelten Methode wird der Sedimentaustrag ereignisbezogen über eine Waage bestimmt. In Kombination mit einer Kippwaage ermöglicht sie die gleichzeitige Messung des Oberflächenabflusses. Die Messapparatur wurde für Gebiete entwickelt, die eine überwiegend grobsandige Textur aufweisen und nur geringe Mengen Ton und Schluff enthalten. Zusätzlich wurden zwei Lasersysteme zur Messung der räumlichen Verteilung der Erosion eingesetzt. Für die erste Methode wurde ein punktuell messender Laser in einer fest installierten Apparatur über die Fläche bewegt und punktuell Höhenunterschiede in einem festen Raster bestimmt. Durch Interpolation konnten Bereiche mit Sedimentabtrag von Akkumulationsbereiche unterschieden werden. Mit dieser Methode können auch größere Flächen vermessen werden (hier 16 m²), allerdings weisen die Messungen in den Übergangsbereichen von Rinne zu Zwischenrille große Fehler auf. Bei der zweiten Methode wird mit einer Messung ein Quadratmeter mit einer hohen räumlichen Auflösung komplett erfasst. Um ein dreidimensionales Bild zu erstellen, müssen insgesamt vier Aufnahmen von jeweils unterschiedlichen Seiten aufgenommen werden. So lassen sich Abtrag und Akkumulation sehr genau bestimmen, allerdings ist die Messung relativ aufwendig und erfasst nur eine kleine Fläche. Zusätzlich wurde der Sedimentaustrag noch auf der Plotskala erfasst. Die Messungen zeigen, korrespondierend zu den Bodeneigenschaften, große Sedimentausträge während des Sommerhalbjahrs und kaum Austräge im Winter. Weiterhin belegen die Ergebnisse eine größere Bedeutung der Rillenerosion gegenüber der Zwischenrillenerosion für Niederschlagsereignisse hoher Intensität (>25 mm/h in einem zehnminütigem Intervall). Im Gegensatz dazu dominierte die Zwischenrillenerosion bei Ereignissen geringerer Intensität (<20 mm/h in einem zehnminütigem Intervall), wobei mindestens 9 mm Niederschlag in einer Intensität von mindesten 3,6 mm/h nötig sind, damit es zur Erosion kommt. Basierend auf den gemessenen Abflüssen und Sedimentausträgen wurden Regressiongleichungen abgeleitet, die eine Berechnung dieser beiden Prozesse für die untersuchte Fläche ermöglichen. Während die Menge an Oberflächenabfluss einen starken Zusammenhang zu der Menge an gefallenem Niederschlag zeigt (r² = 0,9), ist die Berechnung des ausgetragenen Sedimentes eher ungenau (r² = 0,7). Zusammenfassend beschreibt die Arbeit Einflüsse hydrophober Bodeneigenschaften auf verschiedenen Skalen und arbeitet die Auswirkungen, die vor allem auf der kleinen Skala von großer Bedeutung sind, heraus.
Modern acquisition of seismic data on receiver networks worldwide produces an increasing amount of continuous wavefield recordings. Hence, in addition to manual data inspection, seismogram interpretation requires new processing utilities for event detection, signal classification and data visualization. Various machine learning algorithms, which can be adapted to seismological problems, have been suggested in the field of pattern recognition. This can be done either by means of supervised learning using manually defined training data or by unsupervised clustering and visualization. The latter allows the recognition of wavefield patterns, such as short-term transients and long-term variations, with a minimum of domain knowledge. Besides classical earthquake seismology, investigations of temporal patterns in seismic data also concern novel approaches such as noise cross-correlation or ambient seismic vibration analysis in general, which have moved into focus within the last decade. In order to find records suitable for the respective approach or simply for quality control, unsupervised preprocessing becomes important and valuable for large data sets. Machine learning techniques require the parametrization of the data using feature vectors. Applied to seismic recordings, wavefield properties have to be computed from the raw seismograms. For an unsupervised approach, all potential wavefield features have to be considered to reduce subjectivity to a minimum. Furthermore, automatic dimensionality reduction, i.e. feature selection, is required in order to decrease computational cost, enhance interpretability and improve discriminative power. This study presents an unsupervised feature selection and learning approach for the discovery, imaging and interpretation of significant temporal patterns in seismic single-station or network recordings. In particular, techniques permitting an intuitive, quickly interpretable and concise overview of available records are suggested. For this purpose, the data is parametrized by real-valued feature vectors for short time windows using standard seismic analysis tools as feature generation methods, such as frequency-wavenumber, polarization, and spectral analysis. The choice of the time window length is dependent on the expected durations of patterns to be recognized or discriminated. We use Self-Organizing Maps (SOMs) for a data-driven feature selection, visualization and clustering procedure, which is particularly suitable for high-dimensional data sets. Using synthetics composed of Rayleigh and Love waves and three different types of real-world data sets, we show the robustness and reliability of our unsupervised learning approach with respect to the effect of algorithm parameters and data set properties. Furthermore, we approve the capability of the clustering and imaging techniques. For all data, we find improved discriminative power of our feature selection procedure compared to feature subsets manually selected from individual wavefield parametrization methods. In particular, enhanced performance is observed compared to the most favorable individual feature generation method, which is found to be the frequency spectrum. The method is applied to regional earthquake records at the European Broadband Network with the aim to define suitable features for earthquake detection and seismic phase classification. For the latter, we find that a combination of spectral and polarization features favor S wave detection at a single receiver. However, SOM-based visualization of phase discrimination shows that clustering applied to the records of two stations only allows onset or P wave detection, respectively. In order to improve the discrimination of S waves on receiver networks, we recommend to consider additionally the temporal context of feature vectors. The application to continuous recordings of seismicity close to an active volcano (Mount Merapi, Java, Indonesia) shows that two typical volcano-seismic events (VTB and Guguran) can be detected and distinguished by clustering. In contrast, so-called MP events cannot be discriminated. Comparable results are obtained for selected features and recognition rates regarding a previously implemented supervised classification system. Finally, we test the reliability of wavefield clustering to improve common ambient vibration analysis methods such as estimation of dispersion curves and horizontal to vertical spectral ratios. It is found, that in general, the identified short- and long-term patterns have no significant impact on those estimates. However, for individual sites, effects of local sources can be identified. Leaving out the corresponding clusters, yields reduced uncertainties or allows for improving estimation of dispersion curves.
Die funktionelle Bedeutung des Coxsackie- und Adenovirus Rezeptors (CAR) im kolorektalen Karzinom
(2009)
Der Coxsackie- und Adenovirus Rezeptor (CAR) ist als Bestandteil von Tight Junctions (TJ) an interzellulären Adhäsionsprozessen beteiligt und scheint eine wichtige Rolle in der Karzinogenese zu spielen. Diese ist jedoch insbesondere bei Entstehung von Darmkrebs weitgehend unklar. Ziel der Arbeit war es daher, die funktionelle Bedeutung, mögliche Interaktionspartner sowie die Expressionsregulation von CAR im kolorektalen Karzinom zu analysieren. In den Zelllinien CaCo2, Colo205, DLD1, HCT116, HT29, SW480 und T84 konnte die Expression von CAR (mRNA und Protein) nachgewiesen werden. Nach stabiler CAR-Überexpression durch Transfektion von CARcDNA in DLD1, HCT116 und SW480 wurde das Zellwachstum gehemmt und eine Abnahme von Migration und Invasion induziert. Eine stabile CAR-Inhibition nach Transfektion von CARsiRNA führte in diesen Zelllinien zum Anstieg der Proliferation sowie zu verstärkter Migrations- und Invasionsaktivität, die in DLD1 mit morphologischen Änderungen einhergingen. Eine Genexpressionsanalyse der Zelllinie DLD1 mit CAR-Inhibition identifizierte α-Catenin als das am stärksten regulierte Gen. Obwohl keine direkte Interaktion beider Proteine detektiert werden konnte, führte eine stabile Re-Expression von α-Catenin in DLD1 mit stabiler CAR-Inhibition zu einer deutlichen Reduktion von Proliferation, Migration und Invasion sowie zu einem Rückgang der zellmorphologischen Änderungen. Um den Einfluss von Differenzierung auf die Regulation der CAR-Expression zu untersuchen, erfolgte eine Behandlung aller Zelllinien mit Natriumbutyrat. Dies führte in fünf der sieben Zelllinien zu einer Aktivierung des CAR-Promotors sowie zu einer gesteigerten Expression und Immunoreaktivität von CAR an der Zelloberfläche. Die Zelllinie CaCo2 zeigte nach spontaner Differenzierung durch 21-tägiges Wachstum post Konfluenz ebenfalls eine verstärkte CAR-mRNA-Expression sowie eine erhöhte CAR-Präsenz an der Zelloberfläche. Die gewonnenen Daten konnten die funktionelle Bedeutung von CAR für die Kolonkarzinogenese sowie den Einfluss von α-Catenin auf diese Funktion deutlich machen. Es wurde gezeigt, dass die Expressionsregulation sowie die subzelluläre Verteilung von CAR durch den zellulären Differenzierungsstatus beeinflusst werden kann.
Due to the unique environmental conditions and different feedback mechanisms, the Arctic region is especially sensitive to climate changes. The influence of clouds on the radiation budget is substantial, but difficult to quantify and parameterize in models. In the framework of the PhD, elastic backscatter and depolarization lidar observations of Arctic clouds were performed during the international Arctic Study of Tropospheric Aerosol, Clouds and Radiation (ASTAR) from Svalbard in March and April 2007. Clouds were probed above the inaccessible Arctic Ocean with a combination of airborne instruments: The Airborne Mobile Aerosol Lidar (AMALi) of the Alfred Wegener Institute for Polar and Marine Research provided information on the vertical and horizontal extent of clouds along the flight track, optical properties (backscatter coefficient), and cloud thermodynamic phase. From the data obtained by the spectral albedometer (University of Mainz), the cloud phase and cloud optical thickness was deduced. Furthermore, in situ observations with the Polar Nephelometer, Cloud Particle Imager and Forward Scattering Spectrometer Probe (Laboratoire de Météorologie Physique, France) provided information on the microphysical properties, cloud particle size and shape, concentration, extinction, liquid and ice water content. In the thesis, a data set of four flights is analyzed and interpreted. The lidar observations served to detect atmospheric structures of interest, which were then probed by in situ technique. With this method, an optically subvisible ice cloud was characterized by the ensemble of instruments (10 April 2007). Radiative transfer simulations based on the lidar, radiation and in situ measurements allowed the calculation of the cloud forcing, amounting to -0.4 W m-2. This slight surface cooling is negligible on a local scale. However, thin Arctic clouds have been reported more frequently in winter time, when the clouds' effect on longwave radiation (a surface warming of 2.8 W m-2) is not balanced by the reduced shortwave radiation (surface cooling). Boundary layer mixed-phase clouds were analyzed for two days (8 and 9 April 2007). The typical structure consisting of a predominantly liquid water layer on cloud top and ice crystals below were confirmed by all instruments. The lidar observations were compared to European Centre for Medium-Range Weather Forecasts (ECMWF) meteorological analyses. A change of air masses along the flight track was evidenced in the airborne data by a small completely glaciated cloud part within the mixed-phase cloud system. This indicates that the updraft necessary for the formation of new cloud droplets at cloud top is disturbed by the mixing processes. The measurements served to quantify the shortcomings of the ECMWF model to describe mixed-phase clouds. As the partitioning of cloud condensate into liquid and ice water is done by a diagnostic equation based on temperature, the cloud structures consisting of a liquid cloud top layer and ice below could not be reproduced correctly. A small amount of liquid water was calculated for the lowest (and warmest) part of the cloud only. Further, the liquid water content was underestimated by an order of magnitude compared to in situ observations. The airborne lidar observations of 9 April 2007 were compared to space borne lidar data on board of the satellite Cloud-Aerosol Lidar and Infrared Pathfinder Satellite Observations (CALIPSO). The systems agreed about the increase of cloud top height along the same flight track. However, during the time delay of 1 h between the lidar measurements, advection and cloud processing took place, and a detailed comparison of small-scale cloud structures was not possible. A double layer cloud at an altitude of 4 km was observed with lidar at the West coast in the direct vicinity of Svalbard (14 April 2007). The cloud system consisted of two geometrically thin liquid cloud layers (each 150 m thick) with ice below each layer. While the upper one was possibly formed by orographic lifting under the influence of westerly winds, or by the vertical wind shear shown by ECMWF analyses, the lower one might be the result of evaporating precipitation out of the upper layer. The existence of ice precipitation between the two layers supports the hypothesis that humidity released from evaporating precipitation was cooled and consequently condensed as it experienced the radiative cooling from the upper layer. In summary, a unique data set characterizing tropospheric Arctic clouds was collected with lidar, in situ and radiation instruments. The joint evaluation with meteorological analyses allowed a detailed insight in cloud properties, cloud evolution processes and radiative effects.
The presented thesis describes the observations of the Galactic center Quintuplet cluster, the spectral analysis of the cluster Wolf-Rayet stars of the nitrogen sequence to determine their fundamental stellar parameters, and discusses the obtained results in a general context. The Quintuplet cluster was discovered in one of the first infrared surveys of the Galactic center region (Okuda et al. 1987, 1989) and was observed for this project with the ESO-VLT near-infrared integral field instrument SINFONI-SPIFFI. The subsequent data reduction was performed in parts with a self-written pipeline to obtain flux-calibrated spectra of all objects detected in the imaged field of view. First results of the observation were compiled and published in a spectral catalog of 160 flux-calibrated $K$-band spectra in the range of 1.95 to 2.45\,$\mu$m, containing 85 early-type (OB) stars, 62 late-type (KM) stars, and 13 Wolf-Rayet stars. About 100 of these stars are cataloged for the first time. The main part of the thesis project was concentrated on the analysis of the WR stars of the nitrogen sequence and one further identified emission line star (Of/WN) with tailored Potsdam Wolf-Rayet (PoWR) models for expanding atmospheres (Hamann et al. 1995) that are applied to derive the stellar parameters of these stars. For this purpose, the atomic input data of the PoWR models had to be extended by further line transitions in the near-infrared spectral range to enable adaequate model spectra to be calculated. These models were then fitted to the observed spectra, revealing typical paramters for this class of stars. A significant amount of hydrogen of up to $X_\text{H} \sim 0.2$ by mass fraction is still present in their stellar atmospheres. The stars are also found to be very luminous ($\log{(L/L_\odot)} > 6.0$) and show mass-loss rates and wind characteristics typical for radiation-driven winds. By comparison with stellar evolutionary models (Meynet \& Maeder 2003a; Langer et al. 1994), the initial masses were estimated and indicate that the Quintuplet WN stars are descendants from the most massive O stars with $M_\text{init} > 60 M_\odot$ and their ages correspond to a cluster age of 3-5\,million years. The analysis of the individual WN stars revealed an average extinction of $A_K =3.1 \pm 0.5$\,mag ($A_V = 27 \pm 4$) towards the Quintuplet cluster. This extinction was applied to derive the stellar luminosities of the remaining early-type and late-type stars in the catalog and a Hertzsprung-Russell diagram could be compiled. Surprisingly, two stellar populations are found, a group of main sequence OB stars and a group of evolved late-type stars, i.e. red supergiants (RSG). The main sequence stars indicate a cluster age of 4 million years, which would be too young for red supergiants to be already present. A star formation event lasting for a few million years might possibly explain the Quintuplet's population and the cluster would still be considered coeval. However, the unexpected and simultaneous presence of red supergiants and Wolf-Rayet stars in the cluster points out that the details of star formation and cluster evolution are not yet well understood for the Quintuplet cluster.
Fiscal federalism has been an important topic among public finance theorists in the last four decades. There is a series of arguments that decentralization of governments enhances growth by improving allocation efficiency. However, the empirical studies have shown mixed results for industrialized and developing countries and some of them have demonstrated that there might be a threshold level of economic development below which decentralization is not effective. Developing and transition countries have developed a variety of forms of fiscal decentralization as a possible strategy to achieve effective and efficient governmental structures. A generalized principle of decentralization due to the country specific circumstances does not exist. Therefore, decentralization has taken place in different forms in various countries at different times, and even exactly the same extent of decentralization may have had different impacts under different conditions. The purpose of this study is to investigate the current state of the fiscal decentralization in Mongolia and to develop policy recommendations for the efficient and effective intergovernmental fiscal relations system for Mongolia. Within this perspective the analysis concentrates on the scope and structure of the public sector, the expenditure and revenue assignment as well as on the design of the intergovernmental transfer and sub-national borrowing. The study is based on data for twenty-one provinces and the capital city of Mongolia for the period from 2000 to 2009. As a former socialist country Mongolia has had a highly centralized governmental sector. The result of the analysis below revealed that the Mongolia has introduced a number of decentralization measures, which followed a top down approach and were slowly implemented without any integrated decentralization strategy in the last decade. As a result Mongolia became de-concentrated state with fiscal centralization. The revenue assignment is lacking a very important element, for instance significant revenue autonomy given to sub-national governments, which is vital for the efficient service delivery at the local level. According to the current assignments of the expenditure and revenue responsibilities most of the provinces are unable to provide a certain national standard of public goods supply. Hence, intergovernmental transfers from the central jurisdiction to the sub-national jurisdictions play an important role for the equalization of the vertical and horizontal imbalances in Mongolia. The critical problem associated with intergovernmental transfers is that there is not a stable, predictable and transparent system of transfer allocation. The amount of transfers to sub-national governments is determined largely by political decisions on ad hoc basis and disregards local differences in needs and fiscal capacity. Thus a fiscal equalization system based on the fiscal needs of the provinces should be implemented. The equalization transfers will at least partly offset the regional disparities in revenues and enable the sub-national governments to provide a national minimum standard of local public goods.
This study presents noble gas compositions (He, Ne, Ar, Kr, and Xe) of lavas from several Hawaiian volcanoes. Lavas from the Hawaii Scientific Drilling Project (HSDP) core, surface samples from Mauna Kea, Mauna Loa, Kilauea, Hualalai, Kohala and Haleakala as well as lavas from a deep well on the summit of Kilauea were investigated. Noble gases, especially helium, are used as tracers for mantle reservoirs, based on the assumption that high 3He/4He ratios (>8 RA) represent material from the deep and supposedly less degassed mantle, whereas lower ratios (~ 8 RA) are thought to represent the upper mantle. Shield stage Mauna Kea, Kohala and Kilauea lavas yielded MORB-like to moderately high 3He/4He ratios, while 3He/4He ratios in post-shield stage Haleakala lavas are MORB-like. Few samples show 20Ne/22Ne and 21Ne/22Ne ratios different from the atmospheric values, however, Mauna Kea and Kilauea lavas with excess in mantle Ne agree well with the Loihi-Kilauea line in a neon three-isotope plot, whereas one Kohala sample plots on the MORB correlation line. The values in the 4He/40Ar* (40Ar* denotes radiogenic Ar) versus 4He diagram imply open system fractionation of He from Ar, with a deficiency in 4He. Calculated 4He/40Ar*, 3He/22Nes (22NeS denotes solar Ne) and 4He/21Ne ratios for the sample suite are lower than the respective production and primordial ratios, supporting the observation of a fractionation of He from the heavier noble gases, with a depletion of He with respect to Ne and Ar. The depletion of He is interpreted to be partly due to solubility controlled gas loss during magma ascent. However, the preferential He loss suggests that He is more incompatible than Ne and Ar during magmatic processes. In a binary mixing model, the isotopic He and Ne pattern are best explained by a mixture of a MORB-like end-member with a plume like or primordial end-member with a fractionation in 3He/22Ne, represented by a curve parameter r of 15 (r=(³He/²²Ne)MORB/(³He/²²Ne)PLUME or PRIMORDIAL). Whether the high 3He/4He ratios in Hawaiian lavas are indicative of a primitive component within the Hawaiian plume or are rather a product of the crystal-melt- partitioning behavior during partial melting remains to be resolved.
20 Jahre sind mittlerweile vergangen seit die friedliche Protestbewegung zur Abdankung des alten Regimes der Deutschen Demokratischen Republik führte. Im darauf folgenden Jahre kam es zur Wiedervereinigung der beiden deutschen Staaten. Der anschließende Transformationsprozess ist aufgrund der besonderen Umstände in Deutschland einzigartig unter den ehemaligen sozialistischen Staaten Mittel- und Osteuropas. Der Schwerpunkt dieser Arbeit liegt in der Transformation des Verarbeitenden Gewerbes in den Bundesländern Berlin und Brandenburg. Mit der Wiedervereinigung der beiden deutschen Staaten veränderte sich die Situation für die Betriebe im ehemals sozialistischen Teil auf dramatische Weise. Die Auswirkungen werden anhand von Makro- und Mikrodaten analysiert. Untersuchungsgegenstände sind verschiedene ökonomische Indikatoren, wie Zahl von Betrieben und Arbeitsplätzen, Strukturen (nach Größe und Branchen), Umsätze (im In- und Ausland) sowie Investitionen. Der Vergleich von Brandenburg und Ostberlin mit Westberlin bietet dabei die Möglichkeit, Aufschluss über den erreichten Stand des Transformationsprozesses zu erhalten. Die Datenbasis dieser Arbeit besteht neben Angaben aus der Volkswirtschaftlichen Gesamtrechnung der Länder aus verschiedenen betriebsbasierten Erhebungen der amtlichen Statistik. Der Beobachtungszeitraum umfasst dabei die Jahre 1991 bis 2005. Zur Analyse von Betriebs- und Beschäftigungszahlen und ihrer Dynamik steht sogar eine Totalerhebung für die Jahre 1991 bis 2000 zur Verfügung. Ein besonderer Schwerpunkt dieser Arbeit ist die Rolle der Exporte für die betriebliche Entwicklung. Die deutsche Wirtschaftspolitik fördert Unternehmen bei ihrem Schritt auf ausländische Märkte, da man sich von Exporten eine Wachstumsstimulation erhofft. Damit eine solche Förderung auch langfristige positive Effekte entfalten kann, muss einerseits der Export positiven Einfluss auf das Produktivitätswachstum des betreffenden Betriebes haben, und andererseits muss das Exportverhalten eine gewisse Persistenz aufweisen. Beide Bedingungen werden innerhalb der Arbeit detailliert untersucht.
In normal everyday viewing, we perform large eye movements (saccades) and miniature or fixational eye movements. Most of our visual perception occurs while we are fixating. However, our eyes are perpetually in motion. Properties of these fixational eye movements, which are partly controlled by the brainstem, change depending on the task and the visual conditions. Currently, fixational eye movements are poorly understood because they serve the two contradictory functions of gaze stabilization and counteraction of retinal fatigue. In this dissertation, we investigate the spatial and temporal properties of time series of eye position acquired from participants staring at a tiny fixation dot or at a completely dark screen (with the instruction to fixate a remembered stimulus); these time series were acquired with high spatial and temporal resolution. First, we suggest an advanced algorithm to separate the slow phases (named drift) and fast phases (named microsaccades) of these movements, which are considered to play different roles in perception. On the basis of this identification, we investigate and compare the temporal scaling properties of the complete time series and those time series where the microsaccades are removed. For the time series obtained during fixations on a stimulus, we were able to show that they deviate from Brownian motion. On short time scales, eye movements are governed by persistent behavior and on a longer time scales, by anti-persistent behavior. The crossover point between these two regimes remains unchanged by the removal of microsaccades but is different in the horizontal and the vertical components of the eyes. Other analyses target the properties of the microsaccades, e.g., the rate and amplitude distributions, and we investigate, whether microsaccades are triggered dynamically, as a result of earlier events in the drift, or completely randomly. The results obtained from using a simple box-count measure contradict the hypothesis of a purely random generation of microsaccades (Poisson process). Second, we set up a model for the slow part of the fixational eye movements. The model is based on a delayed random walk approach within the velocity related equation, which allows us to use the data to determine control loop durations; these durations appear to be different for the vertical and horizontal components of the eye movements. The model is also motivated by the known physiological representation of saccade generation; the difference between horizontal and vertical components concurs with the spatially separated representation of saccade generating regions. Furthermore, the control loop durations in the model suggest an external feedback loop for the horizontal but not for the vertical component, which is consistent with the fact that an internal feedback loop in the neurophysiology has only been identified for the vertical component. Finally, we confirmed the scaling properties of the model by semi-analytical calculations. In conclusion, we were able to identify several properties of the different parts of fixational eye movements and propose a model approach that is in accordance with the described neurophysiology and described limitations of fixational eye movement control.
The adaptive evolutionary potential of a species or population to cope with omnipresent environmental challenges is based on its genetic variation. Variability at immune genes, such as the major histocompatibility complex (MHC) genes, is assumed to be a very powerful and effective tool to keep pace with diverse and rapidly evolving pathogens. In my thesis, I studied natural levels of variation at the MHC genes, which have a key role in immune defence, and parasite burden in different small mammal species. I assessed the importance of MHC variation for parasite burden in small mammal populations in their natural environment. To understand the processes shaping different patterns of MHC variation I focused on evidence of selection through pathogens upon the host. Further, I addressed the issue of low MHC diversity in populations or species, which could potentially arise as a result from habitat fragmentation and isolation. Despite their key role in the mammalian evolution the marsupial MHC has been rarely investigated. Studies on primarily captive or laboratory bred individuals indicated very little or even no polymorphism at the marsupial MHC class II genes. However, natural levels of marsupial MHC diversity and selection are unknown to date as studies on wild populations are virtually absent. I investigated MHC II variation in two Neotropical marsupial species endemic to the threatened Brazilian Atlantic Forest (Gracilinanus microtarsus, Marmosops incanus) to test whether the predicted low marsupial MHC class II polymorphism proves to be true under natural conditions. For the first time in marsupials I confirmed characteristics of MHC selection that were so far only known from eutherian mammals, birds, and fish: Positive selection on specific codon sites, recombination, and trans-species polymorphism. Beyond that, the two marsupial species revealed considerable differences in their MHC class II diversity. Diversity was rather low in M. incanus but tenfold higher in G. microtarsus, disproving the predicted general low marsupial MHC class II variation. As pathogens are believed to be very powerful drivers of MHC diversity, I studied parasite burden in both host species to understand the reasons for the remarkable differences in MHC diversity. In both marsupial species specific MHC class II variants were associated to either high or low parasite load highlighting the importance of the marsupial MHC class II in pathogen defence. I developed two alternative scenarios with regard to MHC variation, parasite load, and parasite diversity. In the ‘evolutionary equilibrium’ scenario I assumed the species with low MHC diversity, M. incanus, to be under relaxed pathogenic selection and expected low parasite diversity. Alternatively, low MHC diversity could be the result of a recent loss of genetic variation by means of a genetic bottleneck event. Under this ‘unbalanced situation’ scenario, I assumed a high parasite burden in M. incanus due to a lack of resistance alleles. Parasitological results clearly reject the first scenario and point to the second scenario, as M. incanus is distinctly higher parasitised but parasite diversity is relatively equal compared to G. microtarsus. Hence, I suggest that the parasite load in M. incanus is rather the consequence than the cause for its low MHC diversity. MHC variation and its associations to parasite burden have been typically studied within single populations but MHC variation between populations was rarely taken into account. To gain scientific insight on this issue, I chose a common European rodent species. In the yellow necked mouse (Apodemus flavicollis), I investigated the effects of genetic diversity on parasite load not on the individual but on the population level. I included populations, which possess different levels of variation at the MHC as well as at neutrally evolving genetic markers (microsatellites). I was able to show that mouse populations with a high MHC allele diversity are better armed against high parasite burdens highlighting the significance of adaptive genetic diversity in the field of conservation genetics. An individual itself will not directly benefit from its population’s large MHC allele pool in terms of parasite resistance. But confronted with the multitude of pathogens present in the wild a population with a large MHC allele reservoir is more likely to possess individuals with resistance alleles. These results deepen our understanding of the complex causes and processes of evolutionary adaptations between hosts and pathogens.
The Earth’s magnetic field (EMF) is generated by convections in the electrically conducting liquid iron-rich outer core, modified by the Earth’s rotation. A drastic manifestation of the dynamics of this fluid body is the occurrence of geomagnetic field reversals in the Earth’s history but also geomagnetic excursions, which are more frequent features of otherwise stable polarity chrons, but often poorly constrained in the geological record. To better understand the origin of the field, we need to know how the field has varied on different geological timescales. This includes not only information about changes in the ancient field’s direction but also about the absolute intensity (palaeointensity) and the age. This palaeointensity record is needed for compiling a full-vector description of the field. A palaeomagnetic and palaeointensity study on lava flows allows gaining insights about the evolution of the EMF through time and space. However, constraining the EMF evolution over different geological timescales remains a difficult objective due to the paucity of available palaeointensity data. One new alternative approach in palaeointensity studies is the recently proposed multispecimen parallel differential pTRM (MS) method, which has potentially several advantages over the commonly used Thellier method, because it is in theory independent of magnetic domain state, less prone to biasing effects, such as thermal alteration and significantly faster to perform in the laboratory. A study of highly active volcanic regions, such as the Trans-Mexican Volcanic Belt, seems promising when attempting a full-vector reconstruction or when looking for field excursions. One aim of this thesis was to gain new information about the occurrence and global validity of geomagnetic excursions from the Brunhes- or Matuyama Chron. For this purpose some 75 lava flows from within the Trans-Mexican Volcanic Belt were sampled for palaeomagnetic analyses. The scatter of virtual geomagnetic poles from lavas younger than 1.7 Ma was used for estimating palaeosecular variation and was found to be consistent with latitude dependent Model G and other high quality palaeomagnetic data from Mexico. The palaeomagnetic mean-vectors of 56 lavas were correlated to the Geomagnetic Polarity Timescale supplemented with information on geomagnetic excursions. On the grounds of their associated radioisotopic ages, four lavas were tentatively correlated with known excursions from marine records. Two lava flows dating of Brunhes Chron were associated with the Big Lost and Delts/Stage 17 excursions, respectively. From further two flows dating of Matuyama Chron, one flow was associated with either the Santa Rosa- or Kamikatsura excursions, while the other could have been emplaced during the Gilsa excursion. The most significant outcome was the finding that both Brunhes excursional flows display nearly fully reversed directions that deviate almost 180°C from the expected normal polarity direction. This observation could indicate that in particular the Big Lost and Delta/Stage17 excursions may represent other short periods during which the field completed a full reversal for a short time, such as was previously found for other older cryptochrons or tiny wiggles. Another focus of this thesis was set on estimating the feasibility of the new MS method for routine palaeointensity determination. This was accomplished by applying the MS method to samples from 11 historical lava flows from Mexico and Iceland from which the actual field intensity was either known from contemporary observatory data, or deduced from magnetic field models. Comparing observed with expected intensity values allowed to test the accuracy of the MS method. It a was found that the majority of palaeointensity estimates after the MS method yielded results that were very close or indistinguishable within the range of uncertainty from the expected values. However, a general trend towards an overestimate in the palaeointensity was also observed, which, on the grounds of corroborating rock magnetic analyses, was associated with multidomain material. This observation was taken as first evidence that the MS method is not entirely independent of magnetic domain state, as was originally claimed. However, a second experiment in which a modification of the most widely used Thellier method was applied to sister samples from 5 Icelandic flows revealed that, in comparison to the MS method, the latter produced more accurate and statistically better defined palaeointensities. Thus, from these first results, the MS method appeared as a viable alternative for future palaeointensity studies. Subsequently it was attempted to corroborate the directional record from Mexican lavas with palaeointensity data. It was possible to acquire palaeointensity estimates for 32 out of 51 investigated lava flows. These new results revealed that the new MS palaeointensities for Mexico are, with a high degree of statistical significance, around 30% higher than expected. The generally high palaeointensities seem to corroborate the results obtained from historical lava flows in this study and other previous studies on synthetic samples where domain state effects were found to cause overestimates in the palaeointensity of up to 30 per cent in the MS method. The primary process that leads to this overestimate is assigned to an asymmetry in the demagnetisation and remagnetisation process. Yet, this overestimate is expected to be no larger than what might be expected from Thellier experiments performed on samples with a given degree of multidomain behaviour.