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Previous studies suggested that electric and/or magnetic field fluctuations observed in the nighttime topside ionosphere at midlatitudes generally originate from quiet time nocturnal medium-scale traveling ionospheric disturbances (MSTIDs). However, decisive evidences for the connection between the two have been missing. In this study we make use of the multispacecraft observations of midlatitude magnetic fluctuations (MMFs) in the nighttime topside ionosphere by the Swarm constellation. The analysis results show that the area hosting MMFs is elongated in the NW-SE (NE-SW) direction in the Northern (Southern) Hemisphere. The elongation direction and the magnetic field polarization support that the area hosting MMFs is nearly field aligned. All these properties of MMFs suggest that they have close relationship with MSTIDs. Expectation values of root-mean-square field-aligned currents associated with MMFs are up to about 4nA/m(2). MMF coherency significantly drops for longitudinal distances of 1 degrees.
Dual-normal logic programs
(2015)
Disjunctive Answer Set Programming is a powerful declarative programming paradigm with complexity beyond NP. Identifying classes of programs for which the consistency problem is in NP is of interest from the theoretical standpoint and can potentially lead to improvements in the design of answer set programming solvers. One of such classes consists of dual-normal programs, where the number of positive body atoms in proper rules is at most one. Unlike other classes of programs, dual-normal programs have received little attention so far. In this paper we study this class. We relate dual-normal programs to propositional theories and to normal programs by presenting several inter-translations. With the translation from dual-normal to normal programs at hand, we introduce the novel class of body-cycle free programs, which are in many respects dual to head-cycle free programs. We establish the expressive power of dual-normal programs in terms of SE- and UE-models, and compare them to normal programs. We also discuss the complexity of deciding whether dual-normal programs are strongly and uniformly equivalent.
Optical frequency combs (OFC) constitute an array of phase-correlated equidistant spectral lines with nearly equal intensities over a broad spectral range. The adaptations of combs generated in mode-locked lasers proved to be highly efficient for the calibration of high-resolution (resolving power > 50000) astronomical spectrographs. The observation of different galaxy structures or the studies of the Milky Way are done using instruments in the low- and medium resolution range. To such instruments belong, for instance, the Multi Unit Spectroscopic Explorer (MUSE) being developed for the Very Large Telescope (VLT) of the European Southern Observatory (ESO) and the 4-metre Multi-Object Spectroscopic Telescope (4MOST) being in development for the ESO VISTA 4.1 m Telescope. The existing adaptations of OFC from mode-locked lasers are not resolvable by these instruments.
Within this work, a fibre-based approach for generation of OFC specifically in the low- and medium resolution range is studied numerically. This approach consists of three optical fibres that are fed by two equally intense continuous-wave (CW) lasers. The first fibre is a conventional single-mode fibre, the second one is a suitably pumped amplifying Erbium-doped fibre with anomalous dispersion, and the third one is a low-dispersion highly nonlinear optical fibre. The evolution of a frequency comb in this system is governed by the following processes: as the two initial CW-laser waves with different frequencies propagate through the first fibre, they generate an initial comb via a cascade of four-wave mixing processes. The frequency components of the comb are phase-correlated with the original laser lines and have a frequency spacing that is equal to the initial laser frequency separation (LFS), i.e. the difference in the laser frequencies. In the time domain, a train of pre-compressed pulses with widths of a few pico-seconds arises out of the initial bichromatic deeply-modulated cosine-wave. These pulses undergo strong compression in the subsequent amplifying Erbium-doped fibre: sub-100 fs pulses with broad OFC spectra are formed. In the following low-dispersion highly nonlinear fibre, the OFC experience a further broadening and the intensity of the comb lines are fairly equalised. This approach was mathematically modelled by means of a Generalised Nonlinear Schrödinger Equation (GNLS) that contains terms describing the nonlinear optical Kerr effect, the delayed Raman response, the pulse self-steepening, and the linear optical losses as well as the wavelength-dependent Erbium gain profile for the second fibre. The initial condition equation being a deeply-modulated cosine-wave mimics the radiation of the two initial CW lasers. The numerical studies are performed with the help of Matlab scripts that were specifically developed for the integration of the GNLS and the initial condition according to the proposed approach for the OFC generation. The scripts are based on the Fourth-Order Runge-Kutta in the Interaction Picture Method (RK4IP) in combination with the local error method.
This work includes the studies and results on the length optimisation of the first and the second fibre depending on different values of the group-velocity dispersion of the first fibre. Such length optimisation studies are necessary because the OFC have the biggest possible broadband and exhibit a low level of noise exactly at the optimum lengths. Further, the optical pulse build-up in the first and the second fibre was studied by means of the numerical technique called Soliton Radiation Beat Analysis (SRBA). It was shown that a common soliton crystal state is formed in the first fibre for low laser input powers. The soliton crystal continuously dissolves into separated optical solitons as the input power increases. The pulse formation in the second fibre is critically dependent on the features of the pulses formed in the first fibre. I showed that, for low input powers, an adiabatic soliton compression delivering low-noise OFC occurs in the second fibre. At high input powers, the pulses in the first fibre have more complicated structures which leads to the pulse break-up in the second fibre with a subsequent degradation of the OFC noise performance. The pulse intensity noise studies that were performed within the framework of this thesis allow making statements about the noise performance of an OFC. They showed that the intensity noise of the whole system decreases with the increasing value of LFS.
We propose a fibre-based approach for generation of optical frequency combs (OFCs) with the aim of calibration of astronomical spectrographs in the low and medium-resolution range. This approach includes two steps: in the first step, an appropriate state of optical pulses is generated and subsequently moulded in the second step delivering the desired OFC. More precisely, the first step is realised by injection of two continuous-wave (CW) lasers into a conventional single-mode fibre, whereas the second step generates a broad OFC by using the optical solitons generated in step one as initial condition. We investigate the conversion of a bichromatic input wave produced by two initial CW lasers into a train of optical solitons, which happens in the fibre used as step one. Especially, we are interested in the soliton content of the pulses created in this fibre. For that, we study different initial conditions (a single cosine-hump, an Akhmediev breather, and a deeply modulated bichromatic wave) by means of soliton radiation beat analysis and compare the results to draw conclusion about the soliton content of the state generated in the first step. In case of a deeply modulated bichromatic wave, we observed the formation of a collective soliton crystal for low input powers and the appearance of separated solitons for high input powers. An intermediate state showing the features of both, the soliton crystal and the separated solitons, turned out to be most suitable for the generation of OFC for the purpose of calibration of astronomical spectrographs.
KEYCIT 2014
(2015)
In our rapidly changing world it is increasingly important not only to be an expert in a chosen field of study but also to be able to respond to developments, master new approaches to solving problems, and fulfil changing requirements in the modern world and in the job market. In response to these needs key competencies in understanding, developing and using new digital technologies are being brought into focus in school and university programmes. The IFIP TC3 conference "KEYCIT – Key Competences in Informatics and ICT (KEYCIT 2014)" was held at the University of Potsdam in Germany from July 1st to 4th, 2014 and addressed the combination of key competencies, Informatics and ICT in detail. The conference was organized into strands focusing on secondary education, university education and teacher education (organized by IFIP WGs 3.1 and 3.3) and provided a forum to present and to discuss research, case studies, positions, and national perspectives in this field.
Spatio-temporal control of cellular uptake achieved by photoswitchable cell-penetrating peptides
(2015)
The selective uptake of compounds into specific cells of interest is a major objective in cell biology and drug delivery. By incorporation of a novel, thermostable azobenzene moiety we generated peptides that can be switched optically between an inactive state and an active, cell-penetrating state with excellent spatio-temporal control.
The genetic integrity of each organism depends on the faithful segregation of its genome during mitosis. To meet this challenge, a cellular surveillance mechanism, termed the spindle assembly checkpoint (SAC), evolved that monitors the correct attachment of chromosomes and blocks progression through mitosis if corrections are needed. While the central role of the SAC for genome integrity is well established, its functional dissection has been hampered by the limited availability of appropriate small molecule inhibitors. Using a fluorescence polarization-based screen, we identify Mad2 inhibitor-1 (M2I-1), the first small molecule inhibitor targeting the binding of Mad2 to Cdc20, an essential protein-protein interaction (PPI) within the SAC. Based on computational and biochemical analyses, we propose that M2I-1 disturbs conformational dynamics of Mad2 critical for complex formation with Cdc20. Cellular studies revealed that M2I-1 weakens the SAC response, indicating that the compound might be active in cells. Thus, our study identifies the SAC specific complex formation between Mad2 and Cdc20 as a protein-protein interaction that can be targeted by small molecules.
Spatio-temporal control of cellular uptake achieved by photoswitchable cell-penetrating peptides
(2015)
The selective uptake of compounds into specific cells of interest is a major objective in cell biology and drug delivery. By incorporation of a novel, thermostable azobenzene moiety we generated peptides that can be switched optically between an inactive state and an active, cell-penetrating state with excellent spatio-temporal control.
The United Nations Security Council (UNSC) is one of the most important multilateral institutions having the ambition to shape global governance and the only organ of the global community that can adopt legally binding resolutions for the maintenance of international peace and security and, if necessary, authorize the use of force. Created in the aftermath of World War II by its victors, the UNSC’s constellation looks increasingly anachronistic, however, in light of the changing global distribution of power. Adapting the institutional structure and decision-making procedures of the UNSC has proven to be one of the most difficult challenges of the last decades, while it is the institution that has probably been faced with the most vociferous calls for reform. Although there have been changes to the informal ways in which outside actors are drawn into the UNSC’s work and activities, many of the major players in the current international system seem to be deprived from equal treatment in its core patterns of decision-making. Countries such as Brazil, Germany, India and Japan, alongside emerging African nations such as Nigeria and South Africa, are among the states eager to secure permanent representation on the Council. By comparison, selected BRICS countries, China and Russia - in contrast to their role in other multilateral institutions - are permanent members of the UNSC and with this, have been “insiders” for a long time. This renders the situation of the UNSC different from global institutions, in which traditionally, Western powers have dominated the agenda.
Let A be a nonlinear differential operator on an open set X in R^n and S a closed subset of X. Given a class F of functions in X, the set S is said to be removable for F relative to A if any weak solution of A (u) = 0 in the complement of S of class F satisfies this equation weakly in all of X. For the most extensively studied classes F we show conditions on S which guarantee that S is removable for F relative to A.
The role of knowledge in the policy process remains a central theoretical puzzle in policy analysis and political science. This article argues that an important yet missing piece of this puzzle is the systematic exploration of the political use of policy knowledge. While much of the recent debate has focused on the question of how the substantive use of knowledge can improve the quality of policy choices, our understanding of the political use of knowledge and its effects in the policy process has remained deficient in key respects. A revised conceptualization of the political use of knowledge is introduced that emphasizes how conflicting knowledge can be used to contest given structures of policy authority. This allows the analysis to differentiate between knowledge creep and knowledge shifts as two distinct types of knowledge effects in the policy process. While knowledge creep is associated with incremental policy change within existing policy structures, knowledge shifts are linked to more fundamental policy change in situations when the structures of policy authority undergo some level of transformation. The article concludes by identifying characteristics of the administrative structure of policy systems or sectors that make knowledge shifts more or less likely.
It is well established in language acquisition research that monolingual children and adult second language learners misinterpret sentences with the universal quantifier every and make quantifier-spreading errors that are attributed to a preference for a match in number between two sets of objects. The present Visual World eye-tracking study tested bilingual heritage Russian–English adults and investigated how they interpret of sentences like Every alligator lies in a bathtub in both languages. Participants performed a sentence–picture verification task while their eye movements were recorded. Pictures showed three pairs of alligators in bathtubs and two extra objects: elephants (Control condition), bathtubs (Overexhaustive condition), or alligators (Underexhaustive condition). Monolingual adults performed at ceiling in all conditions. Heritage language (HL) adults made 20% q-spreading errors, but only in the Overexhaustive condition, and when they made an error they spent more time looking at the two extra bathtubs during the Verb region. We attribute q-spreading in HL speakers to cognitive overload caused by the necessity to integrate conflicting sources of information, i.e. the spoken sentences in their weaker, heritage, language and attention-demanding visual context, that differed with respect to referential salience.
It is well established in language acquisition research that monolingual children and adult second language learners misinterpret sentences with the universal quantifier every and make quantifier-spreading errors that are attributed to a preference for a match in number between two sets of objects. The present Visual World eye-tracking study tested bilingual heritage Russian-English adults and investigated how they interpret of sentences like Every alligator lies in a bathtub in both languages. Participants performed a sentence-picture verification task while their eye movements were recorded. Pictures showed three pairs of alligators in bathtubs and two extra objects: elephants (Control condition), bathtubs (Overexhaustive condition), or alligators (Underexhaustive condition). Monolingual adults performed at ceiling in all conditions. Heritage language (HL) adults made 20% q-spreading errors, but only in the Overexhaustive condition, and when they made an error they spent more time looking at the two extra bathtubs during the Verb region. We attribute q-spreading in HL speakers to cognitive overload caused by the necessity to integrate conflicting sources of information, i.e. the spoken sentences in their weaker, heritage, language and attention-demanding visual context, that differed with respect to referential salience.
Permafrost inundated since the last glacial maximum is degrading, potentially releasing trapped or stabilized greenhouse gases, but few observations of the depth of ice-bonded permafrost (IBP) below the seafloor exist for most of the arctic continental shelf. We use spectral ratios of the ambient vibration seismic wavefield, together with estimated shear wave velocity from the dispersion curves of surface waves, for estimating the thickness of the sediment overlying the IBP. Peaks in spectral ratios modeled for three-layered 1-D systems correspond with varying thickness of the unfrozen sediment. Seismic receivers were deployed on the seabed around Muostakh Island in the central Laptev Sea, Siberia. We derive depths of the IBP between 3.7 and 20.7m15%, increasing with distance from the shoreline. Correspondence between expected permafrost distribution, modeled response, and observational data suggests that the method is promising for the determination of the thickness of unfrozen sediment.
Many foresight studies concentrate on technological foresight and its impact at the organizational level. However, often these studies overlook the soft factor of employee competences which is critical to adopting technological and organizational changes and to developing the necessary innovation capabilities. This study investigates the theoretical and methodological underdeveloped relationship between technological innovation and social initiated change and the impact on individual competences in a dynamic sector. The setting of our study is the turbulent creative industries as a whole, where creative and artistic expression merges with changing technological progress. In a scenario study we mainly conducted in 2010, we developed a scenario model for competences to combine individual competences with a scenario approach to investigate how competences are important to the sector shift or need to be enhanced in the future. We use primary qualitative data from expert interviews and workshops and secondary data from industry reports to identify thirty-seven influence factors. An influence matrix calculation and a cluster analysis are used to project three different scenarios presenting how future developments of the creative industries will influence the competences needed for creative occupations. Now, five years later, we reflect the accuracy of the developed scenarios via a comparison of today's situation with the situation in the scenarios. We discuss theoretical contributions for the foresight literature and practical implementations for the future of work in general, and in particular for the creative industries case. (C) 2015 Elsevier Inc. All rights reserved.
Parental effects (PE) can be adaptive and improve offspring performance when parents and offspring experience similar environmental conditions. However, it is unknown whether adaptive PE exist also in habitats where such similarity is unlikely due to strong temporal variation. In particular, we do not know whether PE can adapt offspring to fluctuating levels of neighbour competition in such habitats. Here, we tested for adaptive PE in terms of two key environmental factors in a semi-arid annual system, competition and drought. While rainfall was stochastic in the study site, the competitive environment was partly predictable: higher plant densities followed after favourable (rainy) years due to high seed production. We therefore expected PE to adapt the offspring's competitive ability to these (predictable) fluctuations in plant densities, rather than to adapt the offspring's drought tolerance to the (unpredictable) occurrence of intensified drought. Parental plants of Biscutella didyma, an annual Brassicaceae, were raised under favourable watering and under drought conditions. Offspring performance was then tested under a full-factorial combination of two neighbour regimes and six watering levels in the glasshouse. Offspring of parents grown under favourable conditions were stronger competitors. This was associated with a small shift in phenology but not with higher parental seed provisioning. Offspring from parents grown under drought showed no improved drought tolerance. Moreover, no PE were detectable when offspring were grown without neighbours. Our results suggest a novel path of adaptive PE: higher competitive ability was induced in offspring that were more likely to experience high neighbour densities. Together with the lack of adaptive PE towards drought tolerance, this emphasizes that a correlation between parental and offspring environment is crucial for adaptive PE to evolve. Our results also call for the inclusion of competitive effects in future PE studies.Synthesis. This study demonstrates the important role of adaptive PE for plant fitness (regarding competition) but also their limits (regarding drought) in temporally variable environments, based on the predictability of the respective environmental factor.
Aims. To explore the origin of high-velocity gas in the direction of the Large Magellanic Cloud, (LMC) we analyze absorption lines in the ultraviolet spectrum of a Galactic halo star that is located in front of the LMC at d = 9.2(-7.2)(+4.1) kpc distance.
Methods. We study the velocity-component structure of low and intermediate metal ions (CII, SiII, SiIII) in the spectrum of RXJ0439.8-6809, as obtained with the Cosmic Origins Spectrograph (COS) onboard the Hubble Space Telescope (HST), and measure equivalent widths and column densities for these ions. We supplement our COS data with a Far-Ultraviolet Spectroscopic Explorer (FUSE) spectrum of the nearby LMC star Sk-69 59 and with Hi 21 cm data from the Leiden-Argentina-Bonn (LAB) survey.
Results. Metal absorption toward RXJ0439.8-6809 is unambiguously detected in three different velocity components near v(LSR) = 0, + 60, and + 150 km s(-1). The presence of absorption proves that all three gas components are situated in front of the star, thus located in the disk and inner halo of the Milky Way. For the high-velocity cloud (HVC) at v(LSR) = + 150 km s(-1), we derive an oxygen abundance of [O/H] = -0.63 (similar to 0.2 solar) from the neighboring Sk-69 59 sight line, in accordance with previous abundance measurements for this HVC. From the observed kinematics we infer that the HVC hardly participates in the Galactic rotation.
Conclusions. Our study shows that the HVC toward the LMC represents a Milky Way halo cloud that traces low column density gas with relatively low metallicity. We rule out scenarios in which the HVC represents material close to the LMC that stems from a LMC outflow.
We attempt to clarify a great deal of confusion in the literature on what a passive is, and what counts as a passive in different languages. We do this through a detailed investigation of what has been identified as a passive in Vietnamese, sentences with the morphemes bi and duoc. We also compare these to Mandarin Chinese bei. We show that these morphemes are not passive at all: like English auxiliaries, they may occur with either an active complement or a passive one. We clarify this point and what it means to be a passive. Second, sentences with these morphemes and the corresponding sentences without them are truth-conditionally equivalent. We show that the extra meaning they convey is a type of projective, or not-at-issue, meaning that is separate from the at-issue content of the sentence. We provide a detailed syntactic and semantic analysis of Vietnamese, and give arguments for this analysis. We propose that there is no movement in Vietnamese, but there is in Chinese, and this difference accounts for differences between the two languages. We also clarify what agent-oriented adverbs of the 'deliberately' type show, and draw conclusions about English get passives and tough constructions. (C) 2015 Elsevier B.V. All rights reserved.
The Strange-tailed Tyrant Alectrurus risora (Aves: Tyrannidae) is an endemic species of southern South American grasslands that suffered a 90% reduction of its original distribution due to habitat transformation. This has led the species to be classified as globally Vulnerable. By the beginning of the last century, populations were partially migratory and moved south during the breeding season. Currently, the main breeding population inhabits the Ibera wetlands in the province of Corrientes, north-east Argentina, where it is resident all year round. There are two remaining small populations in the province of Formosa, north-east Argentina, and in southern Paraguay, which are separated from the main population by the Parana-Paraguay River and its continuous riverine forest habitat. The populations of Corrientes and Formosa are separated by 300 km and the grasslands between populations are non-continuous due to habitat transformation. We used mtDNA sequences and eight microsatellite loci to test if there were evidences of genetic isolation between Argentinean populations. We found no evidence of genetic structure between populations (Phi(ST) = 0.004, P = 0.32; Fst = 0.01, P = 0.06), which can be explained by either retained ancestral polymorphism or by dispersal between populations. We found no evidence for a recent demographic bottleneck in nuclear loci. Our results indicate that these populations could be managed as a single conservation unit on a regional scale. Conservation actions should be focused on preserving the remaining network of areas with natural grasslands to guarantee reproduction, dispersal and prevent further decline of populations.
The Strange-tailed Tyrant Alectrurus risora (Aves: Tyrannidae) is an endemic species of southern South American grasslands that suffered a 90% reduction of its original distribution due to habitat transformation. This has led the species to be classified as globally Vulnerable. By the beginning of the last century, populations were partially migratory and moved south during the breeding season. Currently, the main breeding population inhabits the Ibera wetlands in the province of Corrientes, north-east Argentina, where it is resident all year round. There are two remaining small populations in the province of Formosa, north-east Argentina, and in southern Paraguay, which are separated from the main population by the Parana-Paraguay River and its continuous riverine forest habitat. The populations of Corrientes and Formosa are separated by 300 km and the grasslands between populations are non-continuous due to habitat transformation. We used mtDNA sequences and eight microsatellite loci to test if there were evidences of genetic isolation between Argentinean populations. We found no evidence of genetic structure between populations (Phi(ST) = 0.004, P = 0.32; Fst = 0.01, P = 0.06), which can be explained by either retained ancestral polymorphism or by dispersal between populations. We found no evidence for a recent demographic bottleneck in nuclear loci. Our results indicate that these populations could be managed as a single conservation unit on a regional scale. Conservation actions should be focused on preserving the remaining network of areas with natural grasslands to guarantee reproduction, dispersal and prevent further decline of populations.
The high-latitudinal thermospheric processes driven by the solar wind and Interplanetary Magnetic Field (IMF) interaction with the Earth magnetosphere are highly variable parts of the complex dynamic plasma environment, which represent the coupled Magnetosphere – Ionosphere – Thermosphere (MIT) system. The solar wind and IMF interactions transfer energy to the MIT system via reconnection processes at the magnetopause. The Field Aligned Currents (FACs) constitute the energetic links between the magnetosphere and the Earth ionosphere. The MIT system depends on the highly variable solar wind conditions, in particular on changes of the strength and orientation of the IMF.
In my thesis, I perform an investigation on the physical background of the complex MIT system using the global physical - numerical, three-dimensional, time-dependent and self-consistent Upper Atmosphere Model (UAM). This model describes the thermosphere, ionosphere, plasmasphere and inner magnetosphere as well as the electrodynamics of the coupled MIT system for the altitudinal range from 80 (60) km up to the 15 Earth radii.
In the present study, I developed and investigated several variants of the high-latitudinal electrodynamic coupling by including the IMF dependence of FACs into the UAM model. For testing, the various variants were applied to simulations of the coupled MIT system for different seasons, geomagnetic activities, various solar wind and IMF conditions. Additionally, these variants of the theoretical model with the IMF dependence were compared with global empirical models. The modelling results for the most important thermospheric parameters like neutral wind and mass density were compared with satellite measurements. The variants of the UAM model with IMF dependence show a good agreement with the satellite observations. In comparison with the empirical models, the improved variants of the UAM model reproduce a more realistic meso-scale structures and dynamics of the coupled MIT system than the empirical models, in particular at high latitudes. The new configurations of the UAM model with IMF dependence contribute to the improvement of space weather prediction.
Island biotas emerge from the interplay between colonisation, speciation and extinction and are often the scene of spectacular adaptive radiations. A common assumption is that insular diversity is at a dynamic equilibrium, but for remote islands, such as Hawaii or Galápagos, this idea remains untested. Here, we reconstruct the temporal accumulation of terrestrial bird species of the Galápagos using a novel phylogenetic method that estimates rates of biota assembly for an entire community. We show that species richness on the archipelago is in an ascending phase and does not tend towards equilibrium. The majority of the avifauna diversifies at a slow rate, without detectable ecological limits. However, Darwin's finches form an exception: they rapidly reach a carrying capacity and subsequently follow a coalescent-like diversification process. Together, these results suggest that avian diversity of remote islands is rising, and challenge the mutual exclusivity of the non-equilibrium and equilibrium ecological paradigms.
Island biotas emerge from the interplay between colonisation, speciation and extinction and are often the scene of spectacular adaptive radiations. A common assumption is that insular diversity is at a dynamic equilibrium, but for remote islands, such as Hawaii or Galápagos, this idea remains untested. Here, we reconstruct the temporal accumulation of terrestrial bird species of the Galápagos using a novel phylogenetic method that estimates rates of biota assembly for an entire community. We show that species richness on the archipelago is in an ascending phase and does not tend towards equilibrium. The majority of the avifauna diversifies at a slow rate, without detectable ecological limits. However, Darwin's finches form an exception: they rapidly reach a carrying capacity and subsequently follow a coalescent-like diversification process. Together, these results suggest that avian diversity of remote islands is rising, and challenge the mutual exclusivity of the non-equilibrium and equilibrium ecological paradigms.
Manganese (Mn) is an essential micronutrient for development and function of the nervous system. Deficiencies in Mn transport have been implicated in the pathogenesis of Huntington's disease (HD), an autosomal dominant neurodegenerative disorder characterized by loss of medium spiny neurons of the striatum. Brain Mn levels are highest in striatum and other basal ganglia structures, the most sensitive brain regions to Mn neurotoxicity. Mouse models of HD exhibit decreased striatal Mn accumulation and HD striatal neuron models are resistant to Mn cytotoxicity. We hypothesized that the observed modulation of Mn cellular transport is associated with compensatory metabolic responses to HD pathology. Here we use an untargeted metabolomics approach by performing ultraperformance liquid chromatography-ion mobility-mass spectrometry (UPLC-IM-MS) on control and HD immortalized mouse striatal neurons to identify metabolic disruptions under three Mn exposure conditions, low (vehicle), moderate (non-cytotoxic) and high (cytotoxic). Our analysis revealed lower metabolite levels of pantothenic acid, and glutathione (GSH) in HD striatal cells relative to control cells. HD striatal cells also exhibited lower abundance and impaired induction of isobutyryl carnitine in response to increasing Mn exposure. In addition, we observed induction of metabolites in the pentose shunt pathway in HD striatal cells after high Mn exposure. These findings provide metabolic evidence of an interaction between the HD genotype and biologically relevant levels of Mn in a striatal cell model with known HD by Mn exposure interactions. The metabolic phenotypes detected support existing hypotheses that changes in energetic processes underlie the pathobiology of both HD and Mn neurotoxicity.
lower development is controlled by the action of key regulatory transcription factors of the MADS-domain family. The function of these factors appears to be highly conserved among species based on mutant phenotypes. However, the conservation of their downstream processes is much less well understood, mostly because the evolutionary turnover and variation of their DNA-binding sites (BSs) among plant species have not yet been experimentally determined. Here, we performed comparative ChIP (chromatin immunoprecipitation)-seq experiments of the MADS-domain transcription factor SEPALLATA3 (SEP3) in two closely related Arabidopsis species: Arabidopsis thaliana and A. lyrata which have very similar floral organ morphology. We found that BS conservation is associated with DNA sequence conservation, the presence of the CArG-box BS motif and on the relative position of the BS to its potential target gene. Differences in genome size and structure can explain that SEP3 BSs in A. lyrata can be located more distantly to their potential target genes than their counterparts in A. thaliana. In A. lyrata, we identified transposition as a mechanism to generate novel SEP3 binding locations in the genome. Comparative gene expression analysis shows that the loss/gain of BSs is associated with a change in gene expression. In summary, this study investigates the evolutionary dynamics of DNA BSs of a floral key-regulatory transcription factor and explores factors affecting this phenomenon.
In this work we present a CMOS high frequency direct immunosensor operating at 6 GHz (C-band) for label free determination of creatinine. The sensor is fabricated in standard 0.13 μm SiGe:C BiCMOS process. The report also demonstrates the ability to immobilize creatinine molecules on a Si3N4 passivation layer of the standard BiCMOS/CMOS process, therefore, evading any further need of cumbersome post processing of the fabricated sensor chip. The sensor is based on capacitive detection of the amount of non-creatinine bound antibodies binding to an immobilized creatinine layer on the passivated sensor. The chip bound antibody amount in turn corresponds indirectly to the creatinine concentration used in the incubation phase. The determination of creatinine in the concentration range of 0.88–880 μM is successfully demonstrated in this work. A sensitivity of 35 MHz/10 fold increase in creatinine concentration (during incubation) at the centre frequency of 6 GHz is gained by the immunosensor. The results are compared with a standard optical measurement technique and the dynamic range and sensitivity is of the order of the established optical indication technique. The C-band immunosensor chip comprising an area of 0.3 mm2 reduces the sensing area considerably, therefore, requiring a sample volume as low as 2 μl. The small analyte sample volume and label free approach also reduce the experimental costs in addition to the low fabrication costs offered by the batch fabrication technique of CMOS/BiCMOS process.
In this work we present a CMOS high frequency direct immunosensor operating at 6 GHz (C-band) for label free determination of creatinine. The sensor is fabricated in standard 0.13 μm SiGe:C BiCMOS process. The report also demonstrates the ability to immobilize creatinine molecules on a Si3N4 passivation layer of the standard BiCMOS/CMOS process, therefore, evading any further need of cumbersome post processing of the fabricated sensor chip. The sensor is based on capacitive detection of the amount of non-creatinine bound antibodies binding to an immobilized creatinine layer on the passivated sensor. The chip bound antibody amount in turn corresponds indirectly to the creatinine concentration used in the incubation phase. The determination of creatinine in the concentration range of 0.88–880 μM is successfully demonstrated in this work. A sensitivity of 35 MHz/10 fold increase in creatinine concentration (during incubation) at the centre frequency of 6 GHz is gained by the immunosensor. The results are compared with a standard optical measurement technique and the dynamic range and sensitivity is of the order of the established optical indication technique. The C-band immunosensor chip comprising an area of 0.3 mm2 reduces the sensing area considerably, therefore, requiring a sample volume as low as 2 μl. The small analyte sample volume and label free approach also reduce the experimental costs in addition to the low fabrication costs offered by the batch fabrication technique of CMOS/BiCMOS process.
Double cyclization of short linear peptides obtained by solid phase peptide synthesis was used to prepare bridged bicyclic peptides (BBPs) corresponding to the topology of bridged bicyclic alkanes such as norbornane. Diastereomeric norbornapeptides were investigated by 1H-NMR, X-ray crystallography and CD spectroscopy and found to represent rigid globular scaffolds stabilized by intramolecular backbone hydrogen bonds with scaffold geometries determined by the chirality of amino acid residues and sharing structural features of β-turns and α-helices. Proteome profiling by capture compound mass spectrometry (CCMS) led to the discovery of the norbornapeptide 27c binding selectively to calmodulin as an example of a BBP protein binder. This and other BBPs showed high stability towards proteolytic degradation in serum.
Double cyclization of short linear peptides obtained by solid phase peptide synthesis was used to prepare bridged bicyclic peptides (BBPs) corresponding to the topology of bridged bicyclic alkanes such as norbornane. Diastereomeric norbornapeptides were investigated by 1H-NMR, X-ray crystallography and CD spectroscopy and found to represent rigid globular scaffolds stabilized by intramolecular backbone hydrogen bonds with scaffold geometries determined by the chirality of amino acid residues and sharing structural features of β-turns and α-helices. Proteome profiling by capture compound mass spectrometry (CCMS) led to the discovery of the norbornapeptide 27c binding selectively to calmodulin as an example of a BBP protein binder. This and other BBPs showed high stability towards proteolytic degradation in serum.
Arsenic-containing fatty acids are a group of fat-soluble arsenic species (arsenolipids) which are present in marine fish and other seafood. Recently, it has been shown that arsenic-containing hydrocarbons, another group of arsenolipids, exert toxicity in similar concentrations comparable to arsenite although the toxic modes of action differ. Hence, a risk assessment of arsenolipids is urgently needed. In this study the cellular toxicity of a saturated (AsFA 362) and an unsaturated (AsFA 388) arsenic-containing fatty acid and three of their proposed metabolites (DMAV, DMAPr and thio-DMAPr) were investigated in human liver cells (HepG2). Even though both arsenic-containing fatty acids were less toxic as compared to arsenic-containing hydrocarbons and arsenite, significant effects were observable at μM concentrations. DMAV causes effects in a similar concentration range and it could be seen that it is metabolised to its highly toxic thio analogue thio-DMAV in HepG2 cells. Nevertheless, DMAPr and thio-DMAPr did not exert any cytotoxicity. In summary, our data indicate that risks to human health related to the presence of arsenic-containing fatty acids in marine food cannot be excluded. This stresses the need for a full in vitro and in vivo toxicological characterisation of these arsenolipids.
Arsenic-containing fatty acids are a group of fat-soluble arsenic species (arsenolipids) which are present in marine fish and other seafood. Recently, it has been shown that arsenic-containing hydrocarbons, another group of arsenolipids, exert toxicity in similar concentrations comparable to arsenite although the toxic modes of action differ. Hence, a risk assessment of arsenolipids is urgently needed. In this study the cellular toxicity of a saturated (AsFA 362) and an unsaturated (AsFA 388) arsenic-containing fatty acid and three of their proposed metabolites (DMAV, DMAPr and thio-DMAPr) were investigated in human liver cells (HepG2). Even though both arsenic-containing fatty acids were less toxic as compared to arsenic-containing hydrocarbons and arsenite, significant effects were observable at μM concentrations. DMAV causes effects in a similar concentration range and it could be seen that it is metabolised to its highly toxic thio analogue thio-DMAV in HepG2 cells. Nevertheless, DMAPr and thio-DMAPr did not exert any cytotoxicity. In summary, our data indicate that risks to human health related to the presence of arsenic-containing fatty acids in marine food cannot be excluded. This stresses the need for a full in vitro and in vivo toxicological characterisation of these arsenolipids.
Recent experiments show that transcription factors (TFs) indeed use the facilitated diffusion mechanism to locate their target sequences on DNA in living bacteria cells: TFs alternate between sliding motion along DNA and relocation events through the cytoplasm. From simulations and theoretical analysis we study the TF-sliding motion for a large section of the DNA-sequence of a common E. coli strain, based on the two-state TF-model with a fast-sliding search state and a recognition state enabling target detection. For the probability to detect the target before dissociating from DNA the TF-search times self-consistently depend heavily on whether or not an auxiliary operator (an accessible sequence similar to the main operator) is present in the genome section. Importantly, within our model the extent to which the interconversion rates between search and recognition states depend on the underlying nucleotide sequence is varied. A moderate dependence maximises the capability to distinguish between the main operator and similar sequences. Moreover, these auxiliary operators serve as starting points for DNA looping with the main operator, yielding a spectrum of target detection times spanning several orders of magnitude. Auxiliary operators are shown to act as funnels facilitating target detection by TFs.
The coordination of cell polarity within the plane of the tissue layer (planar polarity) is crucial for the development of diverse multicellular organisms. Small Rac/Rho-family GTPases and the actin cytoskeleton contribute to planar polarity formation at sites of polarity establishment in animals and plants. Yet, upstream pathways coordinating planar polarity differ strikingly between kingdoms. In the root of Arabidopsis thaliana, a concentration gradient of the phytohormone auxin coordinates polar recruitment of Rho-of-plant (ROP) to sites of polar epidermal hair initiation. However, little is known about cytoskeletal components and interactions that contribute to this planar polarity or about their relation to the patterning machinery. Here, we show that ACTIN7 (ACT7) represents a main actin isoform required for planar polarity of root hair positioning, interacting with the negative modulator ACTIN-INTERACTING PROTEIN1-2 (AIP1-2). ACT7, AIP1-2 and their genetic interaction are required for coordinated planar polarity of ROP downstream of ethylene signalling. Strikingly, AIP1-2 displays hair cell file-enriched expression, restricted by WEREWOLF (WER)-dependent patterning and modified by ethylene and auxin action. Hence, our findings reveal AIP1-2, expressed under control of the WER-dependent patterning machinery and the ethylene signalling pathway, as a modulator of actin-mediated planar polarity.
Patterned differentiation of distinct cell types is essential for the development of multicellular organisms. The root epidermis of Arabidopsis thaliana is composed of alternating files of root hair and non-hair cells and represents a model system for studying the control of cell-fate acquisition. Epidermal cell fate is regulated by a network of genes that translate positional information from the underlying cortical cell layer into a specific pattern of differentiated cells. While much is known about the genes of this network, new players continue to be discovered. Here we show that the SABRE (SAB) gene, known to mediate microtubule organization, anisotropic cell growth and planar polarity, has an effect on root epidermal hair cell patterning. Loss of SAB function results in ectopic root hair formation and destabilizes the expression of cell fate and differentiation markers in the root epidermis, including expression of the WEREWOLF (WER) and GLABRA2 (GL2) genes. Double mutant analysis reveal that wer and caprice (cpc) mutants, defective in core components of the epidermal patterning pathway, genetically interact with sab. This suggests that SAB may act on epidermal patterning upstream of WER and CPC. Hence, we provide evidence for a role of SAB in root epidermal patterning by affecting cell-fate stabilization. Our work opens the door for future studies addressing SAB-dependent functions of the cytoskeleton during root epidermal patterning.
Forcing Earth’s sea level
(2015)
Peak oil is forcing our society to shift from fossil to renewable resources. However, such renewable resources are also scarce, and they too must be used in the most efficient and sustainable way possible. Biorefining is a concept that represents both resource efficiency and sustainability. This approach initiates a cascade use, which means food and feed production before material use, and an energy-related use at the end of the value-added chain. However, sustainability should already start in the fields, on the agricultural side, where the industrially-used biomass is produced. Therefore, the aim of my doctoral thesis is to analyse the sustainable feedstock supply for biorefineries. In contrast to most studies on biorefineries, I focus on the sustainable provision of feedstock and not on the bioengineering processing of whatever feedstock is available.
Grasslands provide a high biomass potential. They are often inefficiently used, so a new utilisation concept based on the biorefining approach can increase the added value from grasslands. Fodder legumes from temporary and permanent grasslands were chosen for this study. Previous research shows that they are a promising feedstock for industrial uses, and their positive environmental impact is an important byproduct to promote sustainable agricultural production systems.
Green Biorefineries are a class of biorefineries that use fresh green biomass, such as grasses or fodder legumes, as feedstock. After fractionation, an organic solution (press juice) forms; this is used for the production of organic acids, chemicals and extracts, as well as fertilisers. A fibre component (press cake) is also created to produce feed, biomaterials and biogas. This thesis examines a specific value chain, using alfalfa and clover/grass as feedstock and generating lactic acid and one type of cattle feed from it. The research question is if biomass production needs to be adapted for the utilisation of fodder legumes in the Green Biorefinery approach. I have attempted to give a holistic analysis of cultivation, processing and utilisation of two specific grassland crops. Field trials with alfalfa and clover/grass at different study sites were carried out to obtain information on biomass quality and quantity depending on the crop, study site and harvest time. The fresh biomass was fractionated with a screw press and the composition of press juices and cakes was analysed. Fermentation experiments took place to determine the usability of press juices for lactic acid production. The harvest time is not of high importance for the quality of press juices as a fermentation medium. For permanent grasslands, late cuts, often needed for reasons of nature conservation, are possible without a major influence on feedstock quality. The press cakes were silaged for feed-value determination.
Following evidence that both intermediate products are suitable feedstocks in the Green Biorefinery approach, I developed a cost-benefit analysis, comparing different production scenarios on a farm. Two standard crop rotations for Brandenburg, producing either only market crops or market crops and fodder legumes for ruminant feed production, were compared to a system that uses the cultivated fodder legumes for the Green Biorefinery value chain instead of only feed production. Timely processing of the raw material is important to maintain quality for industrial uses, so on-site processing at the farm is assumed in Green Biorefinery scenario. As a result, more added value stays in the rural area. Two farm sizes, common for many European regions, were chosen to examine the influence of scale. The cost site of farmers has also been analysed in detail to assess which farm characteristics make production of press juices for biochemical industries viable. Results show that for large farm sizes in particular, the potential profits are high. Additionally, the wider spectrum of marketable products generates new sources of income for farmers.
The holistic analysis of the supply chain provides evidence that the cultivation processes for fodder legumes do not need to be adapted for use in Green Biorefineries. In fact, the new utilisation approach even widens the cultivation and processing spectrum and can increase economic viability of fodder legume production in conventional farming.
Fluid force microscopy combines the positional accuracy and force sensitivity of an atomic
force microscope (AFM) with nanofluidics via a microchanneled cantilever. However, adequate
loading and cleaning procedures for such AFM micropipettes are required for various
application situations. Here, a new frontloading procedure is described for an AFM micropipette
functioning as a force- and pressure-controlled microscale liquid dispenser. This frontloading
procedure seems especially attractive when using target substances featuring high
costs or low available amounts. Here, the AFM micropipette could be filled from the tip side
with liquid from a previously applied droplet with a volume of only a few μL using a short
low-pressure pulse. The liquid-loaded AFM micropipettes could be then applied for experiments
in air or liquid environments. AFM micropipette frontloading was evaluated with the
well-known organic fluorescent dye rhodamine 6G and the AlexaFluor647-labeled antibody
goat anti-rat IgG as an example of a larger biological compound. After micropipette usage,
specific cleaning procedures were tested. Furthermore, a storage method is described, at
which the AFM micropipettes could be stored for a few hours up to several days without drying
out or clogging of the microchannel. In summary, the rapid, versatile and cost-efficient
frontloading and cleaning procedure for the repeated usage of a single AFM micropipette is
beneficial for various application situations from specific surface modifications through to
local manipulation of living cells, and provides a simplified and faster handling for already
known experiments with fluid force microscopy.
Fluid force microscopy combines the positional accuracy and force sensitivity of an atomic
force microscope (AFM) with nanofluidics via a microchanneled cantilever. However, adequate loading and cleaning procedures for such AFM micropipettes are required for various application situations. Here, a new frontloading procedure is described for an AFM micropipette functioning as a force- and pressure-controlled microscale liquid dispenser. This frontloading
procedure seems especially attractive when using target substances featuring high
costs or low available amounts. Here, the AFM micropipette could be filled from the tip side with liquid from a previously applied droplet with a volume of only a few μL using a short low-pressure pulse. The liquid-loaded AFM micropipettes could be then applied for experiments in air or liquid environments. AFM micropipette frontloading was evaluated with the well-known organic fluorescent dye rhodamine 6G and the AlexaFluor647-labeled antibody goat anti-rat IgG as an example of a larger biological compound. After micropipette usage, specific cleaning procedures were tested. Furthermore, a storage method is described, at which the AFM micropipettes could be stored for a few hours up to several days without drying out or clogging of the microchannel. In summary, the rapid, versatile and cost-efficient
frontloading and cleaning procedure for the repeated usage of a single AFM micropipette is beneficial for various application situations from specific surface modifications through to local manipulation of living cells, and provides a simplified and faster handling for already known experiments with fluid force microscopy.
Earthquake clustering has proven the most useful tool to forecast changes in seismicity rates in the short and medium term (hours to months), and efforts are currently being made to extend the scope of such models to operational earthquake forecasting. The overarching goal of the research presented in this thesis is to improve physics-based earthquake forecasts, with a focus on aftershock sequences. Physical models of triggered seismicity are based on the redistribution of stresses in the crust, coupled with the rate-and-state constitutive law proposed by Dieterich to calculate changes in seismicity rate. This type of models are known as Coulomb- rate and-state (CRS) models. In spite of the success of the Coulomb hypothesis, CRS models typically performed poorly in comparison to statistical ones, and they have been underepresented in the operational forecasting context. In this thesis, I address some of these issues, and in particular these questions: (1) How can we realistically model the uncertainties and heterogeneity of the mainshock stress field? (2) What is the effect of time dependent stresses in the postseismic phase on seismicity? I focus on two case studies from different tectonic settings: the Mw 9.0 Tohoku megathrust and the Mw 6.0 Parkfield strike slip earthquake. I study aleatoric uncertainties using a Monte Carlo method. I find that the existence of multiple receiver faults is the most important source of intrinsic stress heterogeneity, and CRS models perform better when this variability is taken into account. Epistemic uncertainties inherited from the slip models also have a significant impact on the forecast, and I find that an ensemble model based on several slip distributions outperforms most individual models. I address the role of postseismic stresses due to aseismic slip on the mainshock fault (afterslip) and to the redistribution of stresses by previous aftershocks (secondary triggering). I find that modeling secondary triggering improves model performance. The effect of afterslip is less clear, and difficult to assess for near-fault aftershocks due to the large uncertainties of the afterslip models. Off-fault events, on the other hand, are less sensitive to the details of the slip distribution: I find that following the Tohoku earthquake, afterslip promotes seismicity in the Fukushima region. To evaluate the performance of the improved CRS models in a pseudo-operational context, I submitted them for independent testing to a collaborative experiment carried out by CSEP for the 2010-2012 Canterbury sequence. Preliminary results indicate that physical models generally perform well compared to statistical ones, suggesting that CRS models may have a role to play in the future of operational forecasting. To facilitate efforts in this direction, and to enable future studies of earthquake triggering by time dependent processes, I have made the code open source. In the final part of this thesis I summarize the capabilities of the program and outline technical aspects regarding performance and parallelization strategies.
Although eye movements during reading are modulated by cognitive processing demands, they also reflect visual sampling of the input, and possibly preparation of output for speech or the inner voice. By simultaneously recording eye movements and the voice during reading aloud, we obtained an output measure that constrains the length of time spent on cognitive processing. Here we investigate the dynamics of the eye-voice span (EVS), the distance between eye and voice. We show that the EVS is regulated immediately during fixation of a word by either increasing fixation duration or programming a regressive eye movement against the reading direction. EVS size at the beginning of a fixation was positively correlated with the likelihood of regressions and refixations. Regression probability was further increased if the EVS was still large at the end of a fixation: if adjustment of fixation duration did not sufficiently reduce the EVS during a fixation, then a regression rather than a refixation followed with high probability. We further show that the EVS can help understand cognitive influences on fixation duration during reading: in mixed model analyses, the EVS was a stronger predictor of fixation durations than either word frequency or word length. The EVS modulated the influence of several other predictors on single fixation durations (SFDs). For example, word-N frequency effects were larger with a large EVS, especially when word N-1 frequency was low. Finally, a comparison of SFDs during oral and silent reading showed that reading is governed by similar principles in both reading modes, although EVS maintenance and articulatory processing also cause some differences. In summary, the EVS is regulated by adjusting fixation duration and/or by programming a regressive eye movement when the EVS gets too large. Overall, the EVS appears to be directly related to updating of the working memory buffer during reading.
Most of the baryonic matter in the Universe resides in a diffuse gaseous phase in-between galaxies consisting mostly of hydrogen and helium. This intergalactic medium (IGM) is distributed in large-scale filaments as part of the overall cosmic web. The luminous extragalactic objects that we can observe today, such as galaxies and quasars, are surrounded by the IGM in the most dense regions within the cosmic web. The radiation of these objects contributes to the so-called ultraviolet background (UVB) which keeps the IGM highly ionized ever since the epoch of reionization.
Measuring the amount of absorption due to intergalactic neutral hydrogen (HI) against extragalactic background sources is a very useful tool to constrain the energy input of ionizing sources into the IGM. Observations suggest that the HI Lyman-alpha effective optical depth, τ_eff, decreases with decreasing redshift, which is primarily due to the expansion of the Universe. However, some studies find a smaller value of the effective optical depth than expected at the specific redshift z~3.2, possibly related to the complete reionization of helium in the IGM and a hardening of the UVB. The detection and possible cause of a decrease in τ_eff at z~3.2 is controversially debated in the literature and the observed features need further explanation.
To better understand the properties of the mean absorption at high redshift and to provide an answer for whether the detection of a τ_eff feature is real we study 13 high-resolution, high signal-to-noise ratio quasar spectra observed with the Ultraviolet and Visual Echelle Spectrograph (UVES) at the Very Large Telescope (VLT). The redshift evolution of the effective optical depth, τ_eff(z), is measured in the redshift range 2.7≤z≤3.6. The influence of metal absorption features is removed by performing a comprehensive absorption-line-fitting procedure.
In the first part of the thesis, a line-parameter analysis of the column density, N, and Doppler parameter, b, of ≈7500 individually fitted absorption lines is performed. The results are in good agreement with findings from previous surveys.
The second (main) part of this thesis deals with the analysis of the redshift evolution of the effective optical depth. The τ_eff measurements vary around the empirical power law τ_eff(z)~(1+z)^(γ+1) with γ=2.09±0.52. The same analysis as for the observed spectra is performed on synthetic absorption spectra. From a comparison between observed and synthetic spectral data it can be inferred that the uncertainties of the τ_eff values are likely underestimated and that the scatter is probably caused by high-column-density absorbers with column densities in the range 15≤logN≤17. In the real Universe, such absorbers are rarely observed, however. Hence, the difference in τ_eff from different observational data sets and absorption studies is most likely caused by cosmic variance. If, alternatively, the disagreement between such data is a result of an too optimistic estimate of the (systematic) errors, it is also possible that all τ_eff measurements agree with a smooth evolution within the investigated redshift range. To explore in detail the different analysis techniques of previous studies an extensive literature comparison to the results of this work is presented in this thesis.
Although a final explanation for the occurrence of the τ_eff deviation in different studies at z~3.2 cannot be given here, our study, which represents the most detailed line-fitting analysis of its kind performed at the investigated redshifts so far, represents another important benchmark for the characterization of the HI Ly-alpha effective optical depth at high redshift and its indicated unusual behavior at z~3.2.
Electron transfer (ET) reactions play a crucial role in the metabolic pathways of all organisms. In biotechnological approaches, the redox properties of the protein cytochrome c (cyt c), which acts as an electron shuttle in the respiratory chain, was utilized to engineer ET chains on electrode surfaces. With the help of the biopolymer DNA, the redox protein assembles into electro active multilayer (ML) systems, providing a biocompatible matrix for the entrapment of proteins.
In this study the characteristics of the cyt c and DNA interaction were defined on the molecular level for the first time and the binding sites of DNA on cyt c were identified. Persistent cyt c/DNA complexes were formed in solution under the assembly conditions of ML architectures, i.e. pH 5.0 and low ionic strength. At pH 7.0, no agglomerates were formed, permitting the characterization of the NMR spectroscopy. Using transverse relaxation-optimized spectroscopy (TROSY)-heteronuclear single quantum coherence (HSQC) experiments, DNAs’ binding sites on the protein were identified. In particular, negatively charged AA residues, which are known interaction sites in cyt c/protein binding were identified as the main contact points of cyt c and DNA.
Moreover, the sophisticated task of arranging proteins on electrode surfaces to create functional ET chains was addressed. Therefore, two different enzyme types, the flavin dependent fructose dehydrogenase (FDH) and the pyrroloquinoline quinone dependent glucose dehydrogenase (PQQ-GDH), were tested as reaction partners of freely diffusing cyt c and cyt c immobilized on electrodes in mono- and MLs. The characterisation of the ET processes was performed by means of electrochemistry and the protein deposition was monitored by microgravimetric measurements. FDH and PQQ-GDH were found to be generally suitable for combination with the cyt c/DNA ML system, since both enzymes interact with cyt c in solution and in the immobilized state. The immobilization of FDH and cyt c was achieved with the enzyme on top of a cyt c monolayer electrode without the help of a polyelectrolyte. Combining FDH with the cyt c/DNA ML system did not succeed, yet. However, the basic conditions for this protein-protein interaction were defined. PQQ-GDH was successfully coupled with the ML system, demonstrating that that the cyt c/DNA ML system provides a suitable interface for enzymes and that the creation of signal chains, based on the idea of co-immobilized proteins is feasible.
Future work may be directed to the investigation of cyt c/DNA interaction under the precise conditions of ML assembly. Therefore, solid state NMR or X-ray crystallography may be required. Based on the results of this study, the combination of FDH with the ML system should be addressed. Moreover, alternative types of enzymes may be tested as catalytic component of the ML assembly, aiming on the development of innovative biosensor applications.
We describe a natural construction of deformation quantisation on a compact symplectic manifold with boundary. On the algebra of quantum observables a trace functional is defined which as usual annihilates the commutators. This gives rise to an index as the trace of the unity element. We formulate the index theorem as a conjecture and examine it by the classical harmonic oscillator.
Plant cell walls are complex structures that underpin plant growth and are widely exploited in diverse human activities thus placing them with a central importance in biology. Cell walls have been a prominent area of research for a long time, but the chemical complexity and diversity of cell walls not just between species, but also within plants, between cell-types, and between cell wall micro-domains pose several challenges. Progress accelerated several-fold in cell wall biology owing to advances in sequencing technology, aided soon thereafter by advances in omics and imaging technologies. This development provides additional perspectives of cell walls across a rapidly growing number of species, highlighting a myriad of architectures, compositions, and functions.
Furthermore, rather than the component centric view, integrative analysis of the different cell wall components across system-levels help to gain a more in-depth understanding of the structure and biosynthesis of the cell envelope and its interactions with the environment.
To this end, in this work three case studies are detailed, all pertaining to the integrative analysis of heterogeneous cell wall related data arising from different system-levels and analytical techniques. A detailed account of multiblock methods is provided and in particular canonical correlation and regression methods of data integration are discussed. In the first integrative analysis, by employing canonical correlation analysis - a multivariate statistical technique to study the association between two datasets - novel insight to the relationship between glycans and phenotypic traits is gained. In addition, sparse partial least squares regression approach that adapts Lasso penalization and allows for the selection of a subset of variables was employed. The second case study focuses on an integrative analysis of images obtained from different spectroscopic techniques. By employing yet another multiblock approach - multiple co-inertia analysis, insitu biochemical composition of cell walls from different cell-types is studied thereby highlighting the common and complementary parts of the two hyperspectral imaging techniques. Finally, the third integrative analysis facilitates gene expression analysis of the Arabidopsis root transcriptome and translatome for the identification of cell wall related genes and compare expression patterns of cell wall synthesis genes. The computational analysis considered correlation and variation of expression across cell-types at both system-levels, and also provides insight into the degree of co-regulatory relationships that are preserved between the two processes.
The integrative analysis of glycan data and phenotypic traits in cotton fibers using canonical methods led to the identification of specific polysaccharides which may play a major role during fiber development for the final fiber characteristics. Furthermore, this analysis provides a base for future studies on glycan arrays in case of developing cotton fibers. The integrative analysis of images from infrared and Raman spectroscopic approaches allowed the coupling of different analytical techniques to characterize complex biological material, thereby, representing various facets of their chemical properties. Moreover, the results from the co-inertia analysis demonstrated that the study was well adapted as it is relevant for coupling data tables in a symmetric way. Several indicators are proposed to investigate how the global and block scores are related. In addition, studying the root cells of \textit{Arabidopsis thaliana} allowed positing a novel pipeline to systematically investigate and integrate the different levels of information available at the global and single-cell level. The conducted analysis also confirms that previously identified key transcriptional activators of secondary cell wall development display highly conserved patterns of transcription and translation across the investigated cell-types. Moreover, the biological processes that display conserved and divergent patterns based on the cell-type-specific expression and translation levels are identified.
Reworking postcolonialism
(2015)
An interdisciplinary collection of essays, Reworking Postcolonialism explores questions of work, precarity, migration, minority and indigenous rights in relation to contemporary globalization. It focuses on the impact of global market forces on the formation of new subject positions among urban dwellers, exiles, and other disenfranchised communities. Bringing together political, economic and literary approaches to texts and events from across the postcolonial world, the essays collected here investigate the transformative effects of the global dissemination of capital and goods and the movements of people. They call for a revision of existing discourses on rights, entitlements and citizenship.
The simulation of the optical properties of supramolecular aggregates requires the development of methods, which are able to treat a large number of coupled chromophores interacting with the environment. Since it is currently not possible to treat large systems by quantum chemistry, the Frenkel exciton model is a valuable alternative. In this work we show how the Frenkel exciton model can be extended in order to explain the excitonic spectra of a specific double-walled tubular dye aggregate explicitly taking into account dispersive energy shifts of ground and excited states due to van der Waals interaction with all surrounding molecules. The experimentally observed splitting is well explained by the site-dependent energy shift of molecules placed at the inner or outer side of the double-walled tube, respectively. Therefore we can conclude that inclusion of the site-dependent dispersive effect in the theoretical description of optical properties of nanoscaled dye aggregates is mandatory.
The simulation of the optical properties of supramolecular aggregates requires the development of methods, which are able to treat a large number of coupled chromophores interacting with the environment. Since it is currently not possible to treat large systems by quantum chemistry, the Frenkel exciton model is a valuable alternative. In this work we show how the Frenkel exciton model can be extended in order to explain the excitonic spectra of a specific double-walled tubular dye aggregate explicitly taking into account dispersive energy shifts of ground and excited states due to van der Waals interaction with all surrounding molecules. The experimentally observed splitting is well explained by the site-dependent energy shift of molecules placed at the inner or outer side of the double-walled tube, respectively. Therefore we can conclude that inclusion of the site-dependent dispersive effect in the theoretical description of optical properties of nanoscaled dye aggregates is mandatory.
cis-Diamminedichloroplatinum(II) (Cisplatin) is one of the most important and frequently used cytostatic drugs for the treatment of various solid tumors. Herein, a laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) method incorporating a fast and simple sample preparation protocol was developed for the elemental mapping of Cisplatin in the model organism Caenorhabditis elegans (C. elegans). The method allows imaging of the spatially-resolved elemental distribution of platinum in the whole organism with respect to the anatomic structure in L4 stage worms at a lateral resolution of 5 μm. In addition, a dose- and time-dependent Cisplatin uptake was corroborated quantitatively by a total reflection X-ray fluorescence spectroscopy (TXRF) method, and the elemental mapping indicated that Cisplatin is located in the intestine and in the head of the worms. Better understanding of the distribution of Cisplatin in this well-established model organism will be instrumental in deciphering Cisplatin toxicity and pharmacokinetics. Since the cytostatic effect of Cisplatin is based on binding the DNA by forming intra- and interstrand crosslinks, the response of poly(ADP-ribose)metabolism enzyme 1 (pme-1) deletion mutants to Cisplatin was also examined. Loss of pme-1, which is the C. elegans ortholog of human poly(ADP-ribose) polymerase 1 (PARP-1) led to disturbed DNA damage response. With respect to survival and brood size, pme-1 deletion mutants were more sensitive to Cisplatin as compared to wildtype worms, while Cisplatin uptake was indistinguishable.
cis-Diamminedichloroplatinum(II) (Cisplatin) is one of the most important and frequently used cytostatic drugs for the treatment of various solid tumors. Herein, a laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) method incorporating a fast and simple sample preparation protocol was developed for the elemental mapping of Cisplatin in the model organism Caenorhabditis elegans (C. elegans). The method allows imaging of the spatially-resolved elemental distribution of platinum in the whole organism with respect to the anatomic structure in L4 stage worms at a lateral resolution of 5 μm. In addition, a dose- and time-dependent Cisplatin uptake was corroborated quantitatively by a total reflection X-ray fluorescence spectroscopy (TXRF) method, and the elemental mapping indicated that Cisplatin is located in the intestine and in the head of the worms. Better understanding of the distribution of Cisplatin in this well-established model organism will be instrumental in deciphering Cisplatin toxicity and pharmacokinetics. Since the cytostatic effect of Cisplatin is based on binding the DNA by forming intra- and interstrand crosslinks, the response of poly(ADP-ribose)metabolism enzyme 1 (pme-1) deletion mutants to Cisplatin was also examined. Loss of pme-1, which is the C. elegans ortholog of human poly(ADP-ribose) polymerase 1 (PARP-1) led to disturbed DNA damage response. With respect to survival and brood size, pme-1 deletion mutants were more sensitive to Cisplatin as compared to wildtype worms, while Cisplatin uptake was indistinguishable.
Recent experiments show that transcription factors (TFs) indeed use the facilitated diffusion mechanism to locate their target sequences on DNA in living bacteria cells: TFs alternate between sliding motion along DNA and relocation events through the cytoplasm. From simulations and theoretical analysis we study the TF-sliding motion for a large section of the DNA-sequence of a common E. coli strain, based on the two-state TF-model with a fast-sliding search state and a recognition state enabling target detection. For the probability to detect the target before dissociating from DNA the TF-search times self-consistently depend heavily on whether or not an auxiliary operator (an accessible sequence similar to the main operator) is present in the genome section. Importantly, within our model the extent to which the interconversion rates between search and recognition states depend on the underlying nucleotide sequence is varied. A moderate dependence maximises the capability to distinguish between the main operator and similar sequences. Moreover, these auxiliary operators serve as starting points for DNA looping with the main operator, yielding a spectrum of target detection times spanning several orders of magnitude. Auxiliary operators are shown to act as funnels facilitating target detection by TFs.
F2 hybrid chlorosis in a cross between the Arabidopsis thaliana accessions Shahdara and Lovvik-5
(2015)
Flower development is controlled by the action of key regulatory transcription factors of the MADS-domain family. The function of these factors appears to be highly conserved among species based on mutant phenotypes. However, the conservation of their downstream processes is much less well understood, mostly because the evolutionary turnover and variation of their DNA-binding sites (BSs) among plant species have not yet been experimentally determined. Here, we performed comparative ChIP (chromatin immunoprecipitation)-seq experiments of the MADS-domain transcription factor SEPALLATA3 (SEP3) in two closely related Arabidopsis species: Arabidopsis thaliana and A. lyrata which have very similar floral organ morphology. We found that BS conservation is associated with DNA sequence conservation, the presence of the CArG-box BS motif and on the relative position of the BS to its potential target gene. Differences in genome size and structure can explain that SEP3 BSs in A. lyrata can be located more distantly to their potential target genes than their counterparts in A. thaliana. In A. lyrata, we identified transposition as a mechanism to generate novel SEP3 binding locations in the genome. Comparative gene expression analysis shows that the loss/gain of BSs is associated with a change in gene expression. In summary, this study investigates the evolutionary dynamics of DNA BSs of a floral key-regulatory transcription factor and explores factors affecting this phenomenon.
Semi-empirical sea-level models (SEMs) exploit physically motivated empirical relationships between global sea level and certain drivers, in the following global mean temperature. This model class evolved as a supplement to process-based models (Rahmstorf (2007)) which were unable to fully represent all relevant processes. They thus failed to capture past sea-level change (Rahmstorf et al. (2012)) and were thought likely to underestimate future sea-level rise. Semi-empirical models were found to be a fast and useful tool for exploring the uncertainties in future sea-level rise, consistently giving significantly higher projections than process-based models.
In the following different aspects of semi-empirical sea-level modelling have been studied. Models were first validated using various data sets of global sea level and temperature. SEMs were then used on the glacier contribution to sea level, and to infer past global temperature from sea-level data via inverse modelling. Periods studied encompass the instrumental period, covered by tide gauges (starting 1700 CE (Common Era) in Amsterdam) and satellites (first launched in 1992 CE), the era from 1000 BCE (before CE) to present, and the full length of the Holocene (using proxy data). Accordingly different data, model formulations and implementations have been used. It could be shown in Bittermann et al. (2013) that SEMs correctly predict 20th century sea-level when calibrated with data until 1900 CE. SEMs also turned out to give better predictions than the Intergovernmental Panel on Climate Change (IPCC) 4th assessment report (AR4, IPCC (2007)) models, for the period from 1961–2003 CE.
With the first multi-proxy reconstruction of global sea-level as input, estimate of the human-induced component of modern sea-level change and projections of future sea-level rise were calculated (Kopp et al. (2016)). It turned out with 90% confidence that more than 40 % of the observed 20th century sea-level rise is indeed anthropogenic. With the new semi-empirical and IPCC (2013) 5th assessment report (AR5) projections the gap between SEM and process-based model projections closes, giving higher credibility to both. Combining all scenarios, from strong mitigation to business as usual, a global sea-level rise of 28–131 cm relative to 2000 CE, is projected with 90% confidence. The decision for a low carbon pathway could halve the expected global sea-level rise by 2100 CE.
Present day temperature and thus sea level are driven by the globally acting greenhouse-gas forcing. Unlike that, the Milankovich forcing, acting on Holocene timescales, results mainly in a northern-hemisphere temperature change. Therefore a semi-empirical model can be driven with northernhemisphere temperatures, which makes it possible to model the main subcomponent of sea-level change over this period. It showed that an additional positive constant rate of the order of the estimated Antarctic sea-level contribution is then required to explain the sea-level evolution over the Holocene. Thus the global sea level, following the climatic optimum, can be interpreted as the sum of a temperature induced sea-level drop and a positive long-term contribution, likely an ongoing response to deglaciation coming from Antarctica.
Motivated by conflicting evidence in the literature, we re-assessed the role of facial feedback when detecting quantitative or qualitative changes in others’ emotional expressions. Fifty-three healthy adults observed self-paced morph sequences where the emotional facial expression either changed quantitatively (i.e., sad-to-neutral, neutral-to-sad, happy-to-neutral, neutral-to-happy) or qualitatively (i.e. from sad to happy, or from happy to sad). Observers held a pen in their own mouth to induce smiling or frowning during the detection task. When morph sequences started or ended with neutral expressions we replicated a congruency effect: Happiness was perceived longer and sooner while smiling; sadness was perceived longer and sooner while frowning. Interestingly, no such congruency effects occurred for transitions between emotional expressions. These results suggest that facial feedback is especially useful when evaluating the intensity of a facial expression, but less so when we have to recognize which emotion our counterpart is expressing.
Motivated by conflicting evidence in the literature, we re-assessed the role of facial feedback when detecting quantitative or qualitative changes in others’ emotional expressions. Fifty-three healthy adults observed self-paced morph sequences where the emotional facial expression either changed quantitatively (i.e., sad-to-neutral, neutral-to-sad, happy-to-neutral, neutral-to-happy) or qualitatively (i.e. from sad to happy, or from happy to sad). Observers held a pen in their own mouth to induce smiling or frowning during the detection task. When morph sequences started or ended with neutral expressions we replicated a congruency effect: Happiness was perceived longer and sooner while smiling; sadness was perceived longer and sooner while frowning. Interestingly, no such congruency effects occurred for transitions between emotional expressions. These results suggest that facial feedback is especially useful when evaluating the intensity of a facial expression, but less so when we have to recognize which emotion our counterpart is expressing.
The paper aims at considering characteristics from one field of contemporary visual studies that has for a long time been neglected in academic research: Pictorial signs on Social Network Sites (SNS) are an outstanding class of semiotic resources that is greatly shaped by processes of technological and collective sign production and distribution. A brief examination of the scholarly research on the pragmatics and semiotics of pictorial signs on SNS shows that the heterogeneity of visual signs is often neglected and that it mostly concentrates on one aspect of these pictorial signs: their technological production or their purpose for individual self-disclosure. The paper therefore considers the semiosis of pictorial signs on SNS in a holistic perspective as one the one hand produced by individual and collective meaning making as well as on the other hand a product of technological framing. It therefore develops a techno-semiotic pragmatic account that takes into consideration both processes. Starting from a prominent class of pictorial signs on SNS during Tunisian Revolution, the Tunisian Flag graphics, the paper than shows that communicative and social interaction functions on the graphic interface of SNS (‘like’-function, sharing and commenting option) are not only directly inscribed into the pictorial frame, but also greatly influence the reading of a pictorial sign. The location of images on the SNS’ interface has an impact on its meaning and on the social functions of a pictorial sign, as profile pictures are directly linked to the online identity of the user. Through technological sign processing, the polysemy of the image is reduced. We therefore consider the images on the one hand as individual self-narratives and on the other as instances of SNS’ visual culture that brings out dominant visual codes but also allows social and political movements to spread.
Enzyme cascade reactions
(2015)
Complementary to the well-established zwitterionic monomer 3-((3-methacrylamidopropyl)dimethylammonio) propane-1-sulfonate (SPP), the closely related monomers 2-hydroxy-3-((3-methacrylamidopropyl) dimethylammonio)propane-1-sulfonate (SHPP) and 4-((3-methacrylamidopropyl)dimethylammonio)-butane-1-sulfonate (SBP) were synthesised and polymerised by reversible addition–fragmentation chain transfer (RAFT) polymerisation, using a fluorophore labeled RAFT agent. The polyzwitterions of systematically varied molar masses were characterised with respect to their solubility in water and aqueous salt solutions. Both poly(sulfobetaine)s show thermoresponsive behaviour in water, exhibiting phase separation at low temperatures and upper critical solution temperatures (UCST). For both polySHPP and polySBP, cloud points depend notably on the molar mass, and are much higher in D2O than in H2O. Also, the cloud points are effectively modulated by the addition of salts. The individual effects can be in parts correlated to the Hofmeister series for the anions studied. Still, they depend in a complex way on the concentration and the nature of the added electrolytes, on the one hand, and on the detailed nature of the spacer group separating the anionic and the cationic charges of the betaine moiety, on the other hand. As anticipated, the cloud points of polySBP are much higher than the ones of the analogous polySPP of identical molar mass. Surprisingly, the cloud points of polySHPP are also somewhat higher than the ones of their polySPP analogues, despite the additional hydrophilic hydroxyl group present in the spacer separating the ammonium and the sulfonate moieties. These findings point to a complicated interplay of the various hydrophilic components in polyzwitterions with respect to their overall hydrophilicity. Thus, the spacer group in the betaine moiety proves to be an effective additional molecular design parameter, apparently small variations of which strongly influence the phase behaviour of the polyzwitterions in specific aqueous environments.
Upconversion NaYF4:Yb:Er nanoparticles co-doped with Gd3+ and Nd3+ for thermometry on the nanoscale
(2015)
In the present work, the upconversion luminescence properties of oleic acid capped NaYF4:Gd3+:Yb3+:Er3+ upconversion nanoparticles (UCNP) with pure β crystal phase and Nd3+ ions as an additional sensitizer were studied in the temperature range of 288 K < T < 328 K. The results of this study showed that the complex interplay of different mechanisms and effects, causing the special temperature behavior of the UCNP can be developed into thermometry on the nanoscale, e.g. to be applied in biological systems on a cellular level. The performance was improved by the use of Nd3+ as an additional dopant utilizing the cascade sensitization mechanism in tri-doped UCNP.
The primary motivation for systematic bases in first principles electronic structure simulations is to derive physical and chemical properties of molecules and solids with predetermined accuracy. This requires a detailed understanding of the asymptotic behaviour of many-particle Coulomb systems near coalescence points of particles. Singular analysis provides a convenient framework to study the asymptotic behaviour of wavefunctions near these singularities. In the present work, we want to introduce the mathematical framework of singular analysis and discuss a novel asymptotic parametrix construction for Hamiltonians of many-particle Coulomb systems. This corresponds to the construction of an approximate inverse of a Hamiltonian operator with remainder given by a so-called Green operator. The Green operator encodes essential asymptotic information and we present as our main result an explicit asymptotic formula for this operator. First applications to many-particle models in quantum chemistry are presented in order to demonstrate the feasibility of our approach. The focus is on the asymptotic behaviour of ladder diagrams, which provide the dominant contribution to shortrange correlation in coupled cluster theory. Furthermore, we discuss possible consequences of our asymptotic analysis with respect to adaptive wavelet approximation.
Obesity is a major health problem for many developing and industrial countries. Increasing rates reach almost 50 % of the population in some countries and related metabolic diseases including cardiovascular events and T2DM are challenging the health systems. Adiposity, an increase in body fat mass, is a major hallmark of obesity. Adipose tissue is long known not only to store lipids but also to influence whole-body metabolism including food intake, energy expenditure and insulin sensitivity. Adipocytes can store lipids and thereby protect other tissue from lipotoxic damage. However, if the energy intake is higher than the energy expenditure over a sustained time period, adipose tissue will expand. This can lead to an impaired adipose tissue function resulting in higher levels of plasma lipids, which can affect other tissue like skeletal muscle, finally leading to metabolic complications. Several studies showed beneficial metabolic effects of weight reduction in obese subjects immediately after weight loss. However, weight regain is frequently observed along with potential negative effects on cardiovascular risk factors and a high intra-individual response.
We performed a body weight maintenance study investigating the mechanisms of weight maintenance after intended WR. Therefore we used a low caloric diet followed by a 12-month life-style intervention. Comprehensive phenotyping including fat and muscle biopsies was conducted to investigate hormonal as well as metabolic influences on body weight regulation. In this study, we showed that weight reduction has numerous potentially beneficial effects on metabolic parameters. After 3-month WR subjects showed significant weight and fat mass reduction, lower TG levels as well as higher insulin sensitivity. Using RNA-Seq to analyse whole fat and muscle transcriptome a strong impact of weight reduction on adipose tissue gene expression was observed. Gene expression alterations over weight reduction included several cellular metabolic genes involved in lipid and glucose metabolism as well as insulin signalling and regulatory pathways. These changes were also associated with anthropometric parameters assigning body composition. Our data indicated that weight reduction leads to a decreased expression of several lipid catabolic as well as anabolic genes. Long-term body weight maintenance might be influenced by several parameters including hormones, metabolic intermediates as well as the transcriptional landscape of metabolic active tissues. Our data showed that genes involved in biosynthesis of unsaturated fatty acids might influence the BMI 18-month after a weight reduction phase. This was further supported by analysing metabolic parameters including RQ and FFA levels. We could show that subjects maintaining their lost body weight had a higher RQ and lower FFA levels, indicating increased metabolic flexibility in subjects.
Using this transcriptomic approach we hypothesize that low expression levels of lipid synthetic genes in adipose tissue together with a higher mitochondrial activity in skeletal muscle tissue might be beneficial in terms of body weight maintenance.
Processes having the same bridges as a given reference Markov process constitute its reciprocal class. In this paper we study the reciprocal class of a continuous time random walk with values in a countable Abelian group, we compute explicitly its reciprocal characteristics and we present an integral characterization of it. Our main tool is a new iterated version of the celebrated Mecke's formula from the point process theory, which allows us to study, as transformation on the path space, the addition of random loops. Thanks to the lattice structure of the set of loops, we even obtain a sharp characterization. At the end, we discuss several examples to illustrate the richness of reciprocal classes. We observe how their structure depends on the algebraic properties of the underlying group.
Microsaccades
(2015)
The first thing we do upon waking is open our eyes. Rotating them in our eye sockets, we scan our surroundings and collect the information into a picture in our head. Eye movements can be split into saccades and fixational eye movements, which occur when we attempt to fixate our gaze. The latter consists of microsaccades, drift and tremor. Before we even lift our eye lids, eye movements – such as saccades and microsaccades that let the eyes jump from one to another position – have partially been prepared in the brain stem. Saccades and microsaccades are often assumed to be generated by the same mechanisms. But how saccades and microsaccades can be classified according to shape has not yet been reported in a statistical manner. Research has put more effort into the investigations of microsaccades’ properties and generation only since the last decade. Consequently, we are only beginning to understand the dynamic processes governing microsaccadic eye movements. Within this thesis, the dynamics governing the generation of microsaccades is assessed and the development of a model for the underlying processes. Eye movement trajectories from different experiments are used, recorded with a video-based eye tracking technique, and a novel method is proposed for the scale-invariant detection of saccades (events of large amplitude) and microsaccades (events of small amplitude). Using a time-frequency approach, the method is examined with different experiments and validated against simulated data. A shape model is suggested that allows for a simple estimation of saccade- and microsaccade related properties. For sequences of microsaccades, in this thesis a time-dynamic Markov model is proposed, with a memory horizon that changes over time and which can best describe sequences of microsaccades.
We define weak boundary values of solutions to those nonlinear differential equations which appear as Euler-Lagrange equations of variational problems. As a result we initiate the theory of Lagrangian boundary value problems in spaces of appropriate smoothness. We also analyse if the concept of mapping degree of current importance applies to the study of Lagrangian problems.