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About 15 years ago, the first Massive Open Online Courses (MOOCs) appeared and revolutionized online education with more interactive and engaging course designs. Yet, keeping learners motivated and ensuring high satisfaction is one of the challenges today's course designers face. Therefore, many MOOC providers employed gamification elements that only boost extrinsic motivation briefly and are limited to platform support. In this article, we introduce and evaluate a gameful learning design we used in several iterations on computer science education courses. For each of the courses on the fundamentals of the Java programming language, we developed a self-contained, continuous story that accompanies learners through their learning journey and helps visualize key concepts. Furthermore, we share our approach to creating the surrounding story in our MOOCs and provide a guideline for educators to develop their own stories. Our data and the long-term evaluation spanning over four Java courses between 2017 and 2021 indicates the openness of learners toward storified programming courses in general and highlights those elements that had the highest impact. While only a few learners did not like the story at all, most learners consumed the additional story elements we provided. However, learners' interest in influencing the story through majority voting was negligible and did not show a considerable positive impact, so we continued with a fixed story instead. We did not find evidence that learners just participated in the narrative because they worked on all materials. Instead, for 10-16% of learners, the story was their main course motivation. We also investigated differences in the presentation format and concluded that several longer audio-book style videos were most preferred by learners in comparison to animated videos or different textual formats. Surprisingly, the availability of a coherent story embedding examples and providing a context for the practical programming exercises also led to a slightly higher ranking in the perceived quality of the learning material (by 4%). With our research in the context of storified MOOCs, we advance gameful learning designs, foster learner engagement and satisfaction in online courses, and help educators ease knowledge transfer for their learners.
Aptamers are single-stranded DNA (ssDNA) or RNA molecules that can bind specifically and with high affinity to target molecules due to their unique three-dimensional structure. For this reason, they are often compared to antibodies and sometimes even referred to as “chemical antibodies”. They are simple and inexpensive to synthesize, easy to modify, and smaller than conventional antibodies. Enzymes, especially hydrolases, are interesting targets in this context. This class of enzymes is capable of hydrolytically cleaving various macromolecules such as proteins, as well as smaller molecules such as antibiotics. Hence, they play an important role in many biological processes including diseases and their treatment. Hydrolase detection as well as the understanding of their function is therefore of great importance for diagnostics and therapy. Due to their various desirable features compared to antibodies, aptamers are being discussed as alternative agents for analytical and diagnostic use in various applications. The use of aptamers in therapy is also frequently investigated, as the binding of aptamers can have effects on the catalytic activity, protein-protein interactions, or proteolytic cascades. Aptamers are generated by an in vitro selection process. Potential aptamer candidates are selected from a pool of enriched nucleic acid sequences with affinity to the target, and their binding affinity and specificity is investigated. This is one of the most important steps in aptamer generation to obtain specific aptamers with high affinity for use in analytical and diagnostic applications. The binding properties or binding domains and their effects on enzyme functions form the basis for therapeutic applications.
In this work, the binding properties of DNA aptamers against two different hydrolases were investigated. In view of their potential utility for analytical methods, aptamers against human urokinase (uPA) and New Delhi metallo-β-lactamase-1 (NDM-1) were evaluated for their binding affinity and specificity using different methods. Using the uPA aptamers, a protocol for measuring the binding kinetics of an aptamer-protein-interaction by surface plasmon resonance spectroscopy (SPR) was developed. Based on the increased expression of uPA in different types of cancer, uPA is discussed as a prognostic and diagnostic tumor marker. As uPA aptamers showed different binding sites on the protein, microtiter plate-based aptamer sandwich assay systems for the detection of uPA were developed. Because of the function of urokinase in cancer cell proliferation and metastasis, uPA is also discussed as a therapeutic target. In this regard, the different binding sites of aptamers showed different effects on uPA function. In vitro experiments demonstrated both inhibition of uPA binding to its receptor as well as the inhibition of uPA catalytic activity for different aptamers. Thus, in addition to their specificity and affinity for their targets, the utility of the aptamers for potential diagnostic and therapeutic applications was demonstrated. First, as an alternative inhibitor of human urokinase for therapeutic purposes, and second, as valuable recognition molecules for the detection of urokinase, as a prognostic and diagnostic marker for cancer, and for NDM-1 to detect resistance to carbapenem antibiotics.
Climate change of anthropogenic origin is affecting Earth’s biodiversity and therefore ecosystems and their services. High latitude ecosystems are even more impacted than the rest of Northern Hemisphere because of the amplified polar warming. Still, it is challenging to predict the dynamics of high latitude ecosystems because of complex interaction between abiotic and biotic components. As the past is the key to the future, the interpretation of past ecological changes to better understand ongoing processes is possible. In the Quaternary, the Pleistocene experienced several glacial and interglacial stages that affected past ecosystems. During the last Glacial, the Pleistocene steppe-tundra was covering most of unglaciated northern hemisphere and disappeared in parallel to the megafauna’s extinction at the transition to the Holocene (~11,700 years ago). The origin of the steppe-tundra decline is not well understood and knowledge on the mechanisms, which caused shifts in past communities and ecosystems, is of high priority as they are likely comparable to those affecting modern ecosystems. Lake or permafrost core sediments can be retrieved to investigate past biodiversity at transitions between glacial and interglacial stages. Siberia and Beringia were the origin of dispersal of the steppe-tundra, which make investigation this area of high priority. Until recently, macrofossils and pollen were the most common approaches. They are designed to reconstruct past composition changes but have limit and biases. Since the end of the 20th century, sedimentary ancient DNA (sedaDNA) can also be investigated. My main objectives were, by using sedaDNA approaches to provide scientific evidence of compositional and diversity changes in the Northern Hemisphere ecosystems at the transition between Quaternary glacial and interglacial stages.
In this thesis, I provide snapshots of entire ancient ecosystems and describe compositional changes between Quaternary glacial and interglacial stages, and confirm the vegetation composition and the spatial and temporal boundaries of the Pleistocene steppe-tundra. I identify a general loss of plant diversity with extinction events happening in parallel of megafauna’ extinction. I demonstrate how loss of biotic resilience led to the collapse of a previously well-established system and discuss my results in regards to the ongoing climate change. With further work to constrain biases and limits, sedaDNA can be used in parallel or even replace the more established macrofossils and pollen approaches as my results support the robustness and potential of sedaDNA to answer new palaeoecological questions such as plant diversity changes, loss and provide snapshots of entire ancient biota.
Search for light primordial black holes with VERITAS using gamma γ-ray and optical observations
(2023)
The Very Energetic Radiation Imaging Telescope Array System (VERITAS) is an array of four imaging atmospheric Cherenkov telescopes (IACTs). VERITAS is sensitive to very-high-energy gamma-rays in the range of 100 GeV to >30 TeV. Hypothesized primordial black holes (PBHs) are attractive targets for IACTs. If they exist, their potential cosmological impact reaches beyond the candidacy for constituents of dark matter. The sublunar mass window is the largest unconstrained range of PBH masses. This thesis aims to develop novel concepts searching for light PBHs with VERITAS. PBHs below the sublunar window lose mass due to Hawking radiation. They would evaporate at the end of their lifetime, leading to a short burst of gamma-rays. If PBHs formed at about 10^15 g, the evaporation would occur nowadays. Detecting these signals might not only confirm the existence of PBHs but also prove the theory of Hawking radiation. This thesis probes archival VERITAS data recorded between 2012 and 2021 for possible PBH signals. This work presents a new automatic approach to assess the quality of the VERITAS data. The array-trigger rate and far infrared temperature are well suited to identify periods with poor data quality. These are masked by time cuts to obtain a consistent and clean dataset which contains about 4222 hours. The PBH evaporations could occur at any location in the field of view or time within this data. Only a blind search can be performed to identify these short signals. This thesis implements a data-driven deep learning based method to search for short transient signals with VERITAS. It does not depend on the modelling of the effective area and radial acceptance. This work presents the first application of this method to actual observational IACT data. This thesis develops new concepts dealing with the specifics of the data and the transient detection method. These are reflected in the developed data preparation pipeline and search strategies. After correction for trial factors, no candidate PBH evaporation is found in the data. Thus, new constraints of the local rate of PBH evaporations are derived. At the 99% confidence limit it is below <1.07 * 10^5 pc^-3 yr^-1. This constraint with the new, independent analysis approach is in the range of existing limits for the evaporation rate.
This thesis also investigates an alternative novel approach to searching for PBHs with IACTs. Above the sublunar window, the PBH abundance is constrained by optical microlensing studies. The sampling speed, which is of order of minutes to hours for traditional optical telescopes, is a limiting factor in expanding the limits to lower masses. IACTs are also powerful instruments for fast transient optical astronomy with up to O(ns) sampling. This thesis investigates whether IACTs might constrain the sublunar window with optical microlensing observations. This study confirms that, in principle, the fast sampling speed might allow extending microlensing searches into the sublunar mass window. However, the limiting factor for IACTs is the modest sensitivity to detect changes in optical fluxes. This thesis presents the expected rate of detectable events for VERITAS as well as prospects of possible future next-generation IACTs. For VERITAS, the rate of detectable microlensing events in the sublunar range is ~10^-6 per year of observation time. The future prospects for a 100 times more sensitive instrument are at ~0.05 events per year.
Supernova remnants are considered to be the primary sources of galactic cosmic rays. These cosmic rays are assumed to be accelerated by the diffusive shock acceleration mechanism, specifically at shocks in the remnants. Particularly in the core-collapse scenario, these supernova remnant shocks expand inside the wind-blown bubbles structured by massive progenitors during their lifetime. Therefore, the complex environment of wind bubbles can influence the particle acceleration and radiation from the remnants. Further, the evolution of massive stars depends on their Zero Age Main Sequence mass, rotation, and metallicity. Consequently, the structures of the wind bubbles generated during the lifetime of massive stars should be considerably different. Hence, the particle acceleration in the core-collapse supernova remnants should vary, not only from the remnants evolving in the uniform environment but also from one another, depending on their progenitor stars.
A core-collapse supernova remnant with a very massive 60 𝑀 ⊙ progenitor star has been considered to study the particle acceleration at the shock considering Bohm-like diffusion. This dissertation demonstrates the modification in particle acceleration and radiation while the remnant propagates through different regions of the wind bubble by impacts from the profiles of gas density, the temperature of the bubble and the magnetic field structure. Subsequently, in this thesis, I discuss the impacts of the non-identical ambient environment of core-collapse supernova remnants on particle spectra and the non-thermal emissions, considering 20 𝑀 ⊙ and 60 𝑀⊙ massive progenitors having different evolutionary tracks. Additionally, I also analyse the effect of cosmic ray streaming instabilities on particle spectra.
To model the particle acceleration in the remnants, I have performed simulations in one-dimensional spherical symmetry using RATPaC code. The transport equation for cosmic rays and magnetic turbulence in test-particle approximation, along with the induction equation for the evolution of the large-scale magnetic field, have been solved simultaneously with the hydrodynamic equations for the expansion of remnants inside the pre-supernova circumstellar medium.
The results from simulations describe that the spectra of accelerated particles in supernova remnants are regulated by density fluctuations, temperature variations, the large-scale magnetic field configuration and scattering turbulence. Although the diffusive shock acceleration mechanism at supernova remnant shock predicts the spectral index of 2 for the accelerated non-thermal particles, I have obtained the particle spectra that deviate from this prediction, in the core-collapse scenario. I have found that the particle spectral index reaches 2.5 for the supernova remnant with 60 𝑀 ⊙ progenitor when the remnant resides inside the shocked wind region of the wind bubble, and this softness persists at later evolutionary stages even with Bohm-like diffusion for accelerated particles. However, the supernova remnant with 20 𝑀 ⊙ progenitor does not demonstrate persistent softness in particle spectra from the influence of the hydrodynamics of the corresponding wind bubble. At later stages of evolution, the particle spectra illustrate softness at higher energies for both remnants as the consequence of the escape of high-energy particles from the remnants while considering the cosmic ray streaming instabilities. Finally, I have probed the emission morphology of remnants that varies depending on the progenitors, particularly in earlier evolutionary stages. This dissertation provides insight into different core-collapse remnants expanding inside wind bubbles, for instance, the calculated gamma-ray spectral index from the supernova remnant with 60 𝑀 ⊙ progenitor at later evolutionary stages is consistent with that of the observed supernova remnants expanding in dense molecular clouds.
The relevance of physical fitness for children’s and adolescents’ health is indisputable and it is crucial to regularly assess and evaluate children’s and adolescents’ individual physical fitness development to detect potential negative health consequences in time. Physical fitness tests are easy-to-administer, reliable, and valid which is why they should be widely used to provide information on performance development and health status of children and adolescents. When talking about development of physical fitness, two perspectives can be distinguished. One perspective is how the physical fitness status of children and adolescents changed / developed over the past decades (i.e., secular trends). The other perspective covers the analyses how physical fitness develops with increasing age due to growth and maturation processes. Although, the development of children’s and adolescents’ physical fitness has been extensively described and analyzed in the literature, still some questions remain to be uncovered that will be addressed in the present doctoral thesis.
Previous systematic reviews and meta-analyses have examined secular trends in children’s and adolescents’ physical fitness. However, considering that those analyses are by now 15 years old and that updates are available only to limited components of physical fitness, it is time to re-analyze the literature and examine secular trends for selected components of physical fitness (i.e., cardiorespiratory endurance, muscle strength, proxies of muscle power, and speed). Fur-thermore, the available studies on children’s development of physical fitness as well as the ef-fects of moderating variables such as age and sex have been investigated within a long-term ontogenetic perspective. However, the effects of age and sex in the transition from pre-puberty to puberty in the ninth year of life using a short-term ontogenetic perspective and the effect of timing of school enrollment on children’s development of physical fitness have not been clearly identified. Therefore, the present doctoral thesis seeks to complement the knowledge of children’s and adolescents’ physical fitness development by updating secular trend analysis in selected components of physical fitness, by examining short-term ontogenetic cross-sectional developmental differences in children`s physical fitness, and by comparing physical fitness of older- and younger-than-keyage children versus keyage-children. These findings provide valuable information about children’s and adolescents’ physical fitness development to help prevent potential deficits in physical fitness as early as possible and consequently ensure a holistic development and a lifelong healthy life.
Initially, a systematic review to provide an ‘update’ on secular trends in selected components of physical fitness (i.e., cardiorespiratory endurance, relative muscle strength, proxies of muscle power, speed) in children and adolescents aged 6 to 18 years was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis statement guidelines. To examine short-term ontogenetic cross-sectional developmental differences and to compare physical fitness of older- and younger-than-keyage children versus keyage-children physical fitness data of 108,295 keyage-children (i.e., aged 8.00 to 8.99 years), 2,586 younger-than-keyage children (i.e., aged 7.00 to 7.99 years), and 26,540 older-than-keyage children (i.e., aged 9.00 to 9.99 years) from the third grade were analyzed. Physical fitness was assessed through the EMOTIKON test battery measuring cardiorespiratory endurance (i.e., 6-min-run test), coordina-tion (i.e., star-run test), speed (i.e., 20-m linear sprint test), and proxies of lower (i.e., standing long jump test) and upper limbs (i.e., ball-push test) muscle power. Statistical inference was based on Linear Mixed Models.
Findings from the systematic review revealed a large initial improvement and an equally large subsequent decline between 1986 and 2010 as well as a stabilization between 2010 and 2015 in cardiorespiratory endurance, a general trend towards a small improvement in relative muscle strength from 1972 to 2015, an overall small negative quadratic trend for proxies of muscle power from 1972 to 2015, and a small-to-medium improvement in speed from 2002 to 2015. Findings from the cross-sectional studies showed that even in a single prepubertal year of life (i.e., ninth year) physical fitness performance develops linearly with increasing chronological age, boys showed better performances than girls in all physical fitness components, and the components varied in the size of sex and age effects. Furthermore, findings revealed that older-than-keyage children showed poorer performance in physical fitness compared to keyage-children, older-than-keyage girls showed better performances than older-than-keyage boys, and younger-than-keyage children outperformed keyage-children.
Due to the varying secular trends in physical fitness, it is recommended to promote initiatives for physical activity and physical fitness for children and adolescents to prevent adverse effects on health and well-being. More precisely, public health initiatives should specifically consider exercising cardiorespiratory endurance and muscle strength because both components showed strong positive associations with markers of health. Furthermore, the findings implied that physical education teachers, coaches, or researchers can utilize a proportional adjustment to individually interpret physical fitness of prepubertal school-aged children. Special attention should be given to the promotion of physical fitness of older-than-keyage children because they showed poorer performance in physical fitness than keyage-children. Therefore, it is necessary to specifically consider this group and provide additional health and fitness programs to reduce their deficits in physical fitness experienced during prior years to guarantee a holistic development.
In the last century, several astronomical measurements have supported that a significant percentage (about 22%) of the total mass of the Universe, on galactic and extragalactic scales, is composed of a mysterious ”dark” matter (DM). DM does not interact with the electromagnetic force; in other words it does not reflect, absorb or emit light. It is possible that DM particles are weakly interacting massive particles (WIMPs) that can annihilate (or decay) into Standard Model (SM) particles, and modern very- high-energy (VHE; > 100 GeV) instruments such as imaging atmospheric Cherenkov telescopes (IACTs) can play an important role in constraining the main properties of such DM particles, by detecting these products. One of the most privileged targets where to look for DM signal are dwarf spheroidal galaxies (dSphs), as they are expected to be high DM-dominated objects with a clean, gas-free environment. Some dSphs could be considered as extended sources, considering the angular resolution of IACTs; their angu- lar resolution is adequate to detect extended emission from dSphs. For this reason, we performed an extended-source analysis, by taking into account in the unbinned maximum likelihood estimation both the energy and the angular extension dependency of observed events. The goal was to set more constrained upper limits on the velocity-averaged cross-section annihilation of WIMPs with VERITAS data. VERITAS is an array of four IACTs, able to detect γ-ray photons ranging between 100 GeV and 30 TeV. The results of this extended analysis were compared against the traditional spectral analysis. We found that a 2D analysis may lead to more constrained results, depending on the DM mass, channel, and source. Moreover, in this thesis, the results of a multi-instrument project are presented too. Its goal was to combine already published 20 dSphs data from five different experiments, such as Fermi-LAT, MAGIC, H.E.S.S., VERITAS and HAWC, in order to set upper limits on the WIMP annihilation cross-section in the widest mass range ever reported.
The first part of the thesis studies the properties of fast mode in magneto hydro-dynamic (MHD) turbulence. 1D and 3D numerical simulations are carried out to generate decaying fast mode MHD turbulence. The injection of waves are carried out in a collinear and isotropic fashion to generate fast mode turbulence. The properties of fast mode turbulence are analyzed by studying their energy spectral density, 2D structure functions and energy decay/cascade time. The injection wave vector is varied to study the dependence of the above properties on the injection wave vectors. The 1D energy spectrum obtained for the velocity and magnetic fields has 𝐸 (𝑘) ∝ 𝑘−2. The 2D energy spectrum and 2D structure functions in parallel and perpendicular directions shows that fast mode turbulence generated is isotropic in nature. The cascade/decay rate of fast mode MHD turbulence is proportional to 𝑘−0.5 for different kinds of wave vector injection. Simulations are also carried out in 1D and 3D to compare balanced and imbalanced turbulence. The results obtained shows that while 1D imbalanced turbulence decays faster than 1D balanced turbulence, there is no difference in the decay of 3D balanced and imbalanced turbulence for the current resolution of 512 grid points.
"The second part of the thesis studies cosmic ray (CR) transport in driven MHD turbulence and is strongly dependent on it’s properties. Test particle simulations are carried out to study CR interaction with both total MHD turbulence and decomposed MHD modes. The spatial diffusion coefficients and the pitch angle scattering diffusion coefficients are calculated from the test particle trajectories in turbulence. The results confirms that the fast modes dominate the CR propagation, whereas Alfvén, slow modes are much less efficient with similar pitch angle scattering rates. The cross field transport on large and small scales are investigated next. On large/global scales, normal diffusion is observed and the diffusion coefficient is suppressed by 𝑀𝜁𝐴 compared to the parallel diffusion coefficients, with 𝜁 closer to 4 in Alfvén modes than that in total turbulence as theoretically expected. For the CR transport on scales smaller than the turbulence injection scale 𝐿, both the local and global magnetic reference frames are adopted. Super diffusion is observed on such small scales in all the cases. Particularly, CR transport in Alfvén modes show clear Richardson diffusion in the local reference frame. The diffusion transition smoothly from the Richardson’s one with index 1.5 to normal diffusion as particle’s mean free path decreases from 𝜆∥ ≫ 𝐿 to 𝜆∥ ≪ 𝐿. These results have broad applications to CRs in various astrophysical environments".
Predicting entrepreneurial development based on individual and business-related characteristics is a key objective of entrepreneurship research. In this context, we investigate whether the motives of becoming an entrepreneur influence the subsequent entrepreneurial development. In our analysis, we examine a broad range of business outcomes including survival and income, as well as job creation, and expansion and innovation activities for up to 40 months after business formation. Using the self-determination theory as conceptual background, we aggregate the start-up motives into a continuous motivational index. We show – based on a unique dataset of German start-ups from unemployment and non-unemployment – that the later business performance is better, the higher they score on this index. Effects are particularly strong for growth-oriented outcomes like innovation and expansion activities. In a next step, we examine three underlying motivational categories that we term opportunity, career ambition, and necessity. We show that individuals driven by opportunity motives perform better in terms of innovation and business expansion activities, while career ambition is positively associated with survival, income, and the probability of hiring employees. All effects are robust to the inclusion of a large battery of covariates that are proven to be important determinants of entrepreneurial performance.
Aging is a complex process characterized by several factors, including loss of genetic and epigenetic information, accumulation of chronic oxidative stress, protein damage and aggregates and it is becoming an emergent drug target. Therefore, it is the utmost importance to study aging and agerelated diseases, to provide treatments to develop a healthy aging process. Skeletal muscle is one of the earliest tissues affected by age-related changes with progressive loss of muscle mass and function from 30 years old, effect known as sarcopenia. Several studies have shown the accumulation of protein aggregates in different animal models, as well as in humans, suggesting impaired proteostasis, a hallmark of aging, especially regarding degradation systems. Thus, different publications have explored the role of the main proteolytic systems in skeletal muscle from rodents and humans, like ubiquitin proteasomal system (UPS) and autophagy lysosomal system (ALS), however with contradictory results. Yet, most of the published studies are performed in muscles that comprise more than one fiber type, that means, muscles composed by slow and fast fibers. These fiber types, exhibit different metabolism and contraction speed; the slow fibers or type I display an oxidative metabolism, while fast fibers function towards a glycolytic metabolism ranging from fast oxidative to fast glycolytic fibers. To this extent, the aim of this thesis sought to understand on how aging impacts both fiber types not only regarding proteostasis but also at a metabolome and transcriptome network levels. Therefore, the first part of this thesis, presents the differences between slow oxidative (from Soleus muscle) and fast glycolytic fibers (Extensor digitorum longus, EDL) in terms of degradation systems and how they cope with oxidative stress during aging, while the second part explores the differences between young and old EDL muscle transcriptome and metabolome, unraveling molecular features. More specifically, the results from the present work show that slow oxidative muscle performs better at maintaining the function of UPS and ALS during aging than EDL muscle, which is clearly affected, accounting for the decline in the catalytic activity rates and accumulation of autophagy-related proteins. Strinkingly, transcriptome and metabolome analyses reveal that fast glycolytic muscle evidences significant downregulation of mitochondrial related processes and damaged mitochondria morphology during aging, despite of having a lower oxidative metabolism compared to oxidative fibers. Moreover, predictive analyses reveal a negative association between aged EDL gene signature and lifespan extending interventions such as caloric restriction (CR). Although, CR intervention does not alter the levels of mitochondrial markers in aged EDL muscle, it can reverse the higher mRNA levels of muscle damage markers. Together, the results from this thesis give new insights about how different metabolic muscle fibers cope with age-related changes and why fast glycolytic fibers are more susceptible to aging than slow oxidative fibers.
Public opinion polls have become vital and increasingly visible parts of election campaigns. Previous research has frequently demonstrated that polls can influence both citizens' voting intentions and political parties' campaign strategies. However, they are also fraught with uncertainty. Margins of error can reflect (parts of) this uncertainty. This paper investigates how citizens' voting intentions change due to whether polling estimates are presented with or without margins of error.
Using a vignette experiment (N=3224), we examine this question based on a real-world example in which different election polls were shown to nationally representative respondents ahead of the 2021 federal election in Germany. We manipulated the display of the margins of error, the interpretation of polls and the closeness of the electoral race.
The results indicate that margins of error can influence citizens' voting intentions. This effect is dependent on the actual closeness of the race and additional interpretative guidance provided to voters. More concretely, the results consistently show that margins of error increase citizens' inclination to vote for one of the two largest contesting parties if the polling gap between these parties is small, and an interpretation underlines this closeness.
The findings of this study are important for three reasons. First, they help to determine whether margins of error can assist citizens in making more informed (strategic) vote decisions. They shed light on whether depicting opinion-poll uncertainty affects the key features of representative democracy, such as democratic accountability. Second, the results stress the responsibility of the media. The way polls are interpreted and contextualized influences the effect of margins of error on voting behaviour. Third, the findings of this paper underscore the significance of including methodological details when communicating scientific research findings to the broader public.
A biological trade-off situation denotes the dependence between traits whereby an increase in the value of one of the traits leads to a decrease in the value of at least one of the others. Understanding trade-offs in cellular systems is relevant to understanding the limits and constraints to tuning desired phenotypes. Therefore, it is mainly the case for rates (i.e. fluxes) of biochemical reactions that shape not only molecular traits, like metabolite concentrations but also determine physiological traits, like growth. Intracellular fluxes are the final phenotype from transcriptional and (post)translational regulation. Quantifying intracellular fluxes provides insights into cellular physiology under particular growth conditions and can be used to characterize the metabolic activity of different pathways. However, estimating fluxes from labelling experiments is labour-intensive; therefore, developing approaches to accurately and precisely predict intracellular fluxes is essential. This thesis addresses two main problems: (i) identifying flux trade-offs and (ii) predicting accurate and precise reaction flux at a genome-scale level. To this end, the concept of an absolute flux trade-off is defined, and a constraint-based approach, termed FluTO, was developed to identify absolute flux trade-offs. FluTO is cast as a mixed integer programming approach applied to genome-scale metabolic models of E. coli, S. cerevisiae, and A. thaliana, imposing realistic constraints on growth and nutrient uptake.. The findings showed that trade-offs are not only species-specific but also specific to carbon sources. In addition, we found that different models of a single species have a different number of reactions in trade-offs. We also showed that absolute flux trade-offs depend on the biomass reaction used to model the growth of A. thaliana under different carbon and nitrogen conditions. Findings reflect the strong relation between nitrogen, carbon, and sulphur metabolisms in the leaves of C3 plants. The concept of relative trade-offs was introduced to further study trade-offs in metabolic networks. A constraint-based approach, FluTOr, was proposed to identify reactions whose fluxes are in relative trade-off concerning an optimized fitness-related cellular task, like growth. FluTOr was employed to find the relative flux trade-offsin the genome-scale metabolic networks of E. coli, S. cerevisiae, and A. thaliana. The results showed that in contrast to the A. thaliana model, the relative trade-offs in the two microorganisms depend on the carbon source, reflecting the differences in the underlying metabolic network. Furthermore, applying FluTOr also showed that reactions that participated in relative trade-offs were implicated in cofactor biosynthesis in the two microorganisms. Prediction of reaction fluxes in the constraint-based metabolic framework is usually performed by parsimonious flux balance analysis (pFBA), employing the principle of efficient usage of protein resources. However, we argued that principles related to the coordination of flux values, neglected in previous studies, provide other means to predict intracellular fluxes. To this end, we designed a constraint-based approach, termed complex-balanced FBA (cbFBA), to predict steady-state flux distributions that maximize the number of balanced complexes in a flux distribution, whereby multi-reaction dependencies are maximized. The comparative analysis showed a better agreement of the flux distributions resulting from cbFBA compared to pFBA with experimentally measured fluxes from 17 E. coli strains and 26 S. cerevisiae knock-out mutants. The results also showed that the predictions from cbFBA are more precise than those from pFBA since cbFBA results in a smaller space of alternative solutions than pFBA.
The emerging threat of antibiotic-resistant bacteria has become a global challenge in the last decades, leading to a rising demand for alternative treatments for bacterial infections. One approach is to target the bacterial cell envelope, making understanding its biophysical properties crucial. Specifically, bacteriophages use the bacterial envelope as an entry point to initiate infection, and they are considered important building blocks of new antibiotic strategies against drug-resistant bacteria.. Depending on the structure of the cell wall, bacteria are classified as Gram-negative and Gram-positive. Gram-negative bacteria are equipped with a complex cell envelope composed of two lipid membranes enclosing a rigid peptidoglycan layer. The synthesis machinery of the Gram-negative cell envelope is the target of antimicrobial agents, including new physical sanitizing procedures addressing the outer membrane (OM). It is therefore very important to study the biophysical properties of the Gram-negative bacterial cell envelope. The high complexity of the Gram-negative OM sets the demand for a model system in which the contribution of individual components can be evaluated separately. In this respect, giant unilamellar vesicles (GUVs) are promising membrane systems to study membrane properties while controlling parameters such as membrane composition and surrounding medium conditions.
The aim of this work was to develop methods and approaches for the preparation and characterization of a GUV-based membrane model that mimics the OM of the Gram-negative cell envelope. A major component of the OM is the lipopolysaccharide (LPS) on the outside of the OM heterobilayer. The vesicle model was designed to contain LPS in the outer leaflet and lipids in the inner leaflet. Furthermore, the interaction of the prepared LPS-GUVs with bacteriophages was tested. LPS containing GUVs were prepared by adapting the inverted emulsion technique to meet the challenging properties of LPS, namely their high self-aggregation rate in aqueous solutions. Notably, an additional emulsification step together with the adaption of solution conditions was employed to asymmetrically incorporate LPS containing long polysaccharide chains into the artificial membranes. GUV membrane asymmetry was verified with a fluorescence quenching assay. Since the necessary precautions for handling the quenching agent sodium dithionite are often underestimated and poorly described, important parameters were tested and identified to obtain a stable and reproducible assay. In the context of varied LPS incorporation, a microscopy-based technique was introduced to determine the LPS content on individual GUVs and to directly compare vesicle properties and LPS coverage. Diffusion coefficient measurements in the obtained GUVs showed that increasing LPS concentrations in the membranes resulted in decreased diffusivity.
Employing LPS-GUVs we could demonstrate that a Salmonella bacteriophage bound with high specificity to its LPS receptor when presented at the GUV surface, and that the number of bound bacteriophages scaled with the amount of presented LPS receptor. In addition to binding, the bacteriophages were able to eject their DNA into the vesicle lumen. LPS-GUVs thus provide a starting platform for bottom-up approaches for the generation of more complex membranes, in which the effects of individual components on the membrane properties and the interaction with antimicrobial agents such as bacteriophages could be explored.
Aquatic ecosystems are frequently overlooked as fungal habitats, although there is increasing evidence that their diversity and ecological importance are greater than previously considered. Aquatic fungi are critical and abundant components of nutrient cycling and food web dynamics, e.g., exerting top-down control on phytoplankton communities and forming symbioses with many marine microorganisms. However, their relevance for microphytobenthic communities is almost unexplored. In the light of global warming, polar regions face extreme changes in abiotic factors with a severe impact on biodiversity and ecosystem functioning. Therefore, this study aimed to describe, for the first time, fungal diversity in Antarctic benthic habitats along the salinity gradient and to determine the co-occurrence of fungal parasites with their algal hosts, which were dominated by benthic diatoms. Our results reveal that Ascomycota and Chytridiomycota are the most abundant fungal taxa in these habitats. We show that also in Antarctic waters, salinity has a major impact on shaping not just fungal but rather the whole eukaryotic community composition, with a diversity of aquatic fungi increasing as salinity decreases. Moreover, we determined correlations between putative fungal parasites and potential benthic diatom hosts, highlighting the need for further systematic analysis of fungal diversity along with studies on taxonomy and ecological roles of Chytridiomycota.
Reactive eutectic media based on ammonium formate for the valorization of bio-sourced materials
(2023)
In the last several decades eutectic mixtures of different compositions were successfully used as solvents for vast amount of chemical processes, and only relatively recently they were discovered to be widely spread in nature. As such they are discussed as a third liquid media of the living cell, that is composed of common cell metabolites. Such media may also incorporate water as a eutectic component in order to regulate properties such as enzyme activity or viscosity. Taking inspiration form such sophisticated use of eutectic mixtures, this thesis will explore the use of reactive eutectic media (REM) for organic synthesis. Such unconventional media are characterized by the reactivity of their components, which means that mixture may assume the role of the solvent as well as the reactant itself.
The thesis focuses on novel REM based on ammonium formate and investigates their potential for the valorization of bio-sourced materials. The use of REM allows the performance of a number of solvent-free reactions, which entails the benefits of a superior atom and energy economy, higher yields and faster rates compared to reactions in solution. This is evident for the Maillard reaction between ammonium formate and various monosaccharides for the synthesis of substituted pyrazines as well as for a Leuckart type reaction between ammonium formate and levulinic acid for the synthesis of 5-methyl-2-pyrrolidone. Furthermore, reaction of ammonium formate with citric acid for the synthesis of yet undiscovered fluorophores, shows that synthesis in REM can open up unexpected reaction pathways.
Another focus of the thesis is the study of water as a third component in the REM. As a result, the concept of two different dilution regimes (tertiary REM and in REM in solvent) appears useful for understanding the influence of water. It is shown that small amounts of water can be of great benefit for the reaction, by reducing viscosity and at the same time increasing reaction yields.
REM based on ammonium formate and organic acids are employed for lignocellulosic biomass treatment. The thesis thereby introduces an alternative approach towards lignocellulosic biomass fractionation that promises a considerable process intensification by the simultaneous generation of cellulose and lignin as well as the production of value-added chemicals from REM components. The thesis investigates the generated cellulose and the pathway to nanocellulose generation and also includes the structural analysis of extracted lignin.
Finally, the thesis investigates the potential of microwave heating to run chemical reactions in REM and describes the synergy between these two approaches. Microwave heating for chemical reactions and the use of eutectic mixtures as alternative reaction media are two research fields that are often described in the scope of green chemistry. The thesis will therefore also contain a closer inspection of this terminology and its greater goal of sustainability.
Carbon nitride semiconductors: properties and application as photocatalysts in organic synthesis
(2023)
Graphitic carbon nitrides (g-CNs) are represented by melon-type g-CN, poly(heptazine imides) (PHIs), triazine-based g-CN and poly(triazine imide) with intercalated LiCl (PTI/Li+Cl‒). These materials are composed of sp2-hybridized carbon and nitrogen atoms; C:N ratio is close to 3:4; the building unit is 1,3,5-triazine or tri-s-triazine; the building units are interconnected covalently via sp2-hybridized nitrogen atoms or NH-moieties; the layers are assembled into a stack via weak van der Waals forces as in graphite. Due to medium band gap (~2.7 eV) g-CNs, such as melon-type g-CN and PHIs, are excited by photons with wavelength ≤ 460 nm. Since 2009 g-CNs have been actively studied as photocatalysts in evolution of hydrogen and oxygen – two half-reactions of full water splitting, by employing corresponding sacrificial agents. At the same time application of g-CNs as photocatalysts in organic synthesis has been remaining limited to few reactions only. Cumulative Habilitation summarizes research work conducted by the group ‘Innovative Heterogeneous Photocatalysis’ between 2017-2023 in the field of carbon nitride organic photocatalysis, which is led by Dr. Oleksandr Savatieiev.
g-CN photocatalysts activate molecules, i.e. generate their more reactive open-shell intermediates, via three modes: i) Photoinduced electron transfer (PET); ii) Excited state proton-coupled electron transfer (ES-PCET) or direct hydrogen atom transfer (dHAT); iii) Energy transfer (EnT). The scope of reactions that proceed via oxidative PET, i.e. one-electron oxidation of a substrate to the corresponding radical cation, are represented by synthesis of sulfonylchlorides from S-acetylthiophenols. The scope of reactions that proceed via reductive PET, i.e. one-electron reduction of a substrate to the corresponding radical anion, are represented by synthesis of γ,γ-dichloroketones from the enones and chloroform.
Due to abundance of sp2-hybridized nitrogen atoms in the structure of g-CN materials, they are able to cleave X-H bonds in organic molecules and store temporary hydrogen atom. ES-PCET or dHAT mode of organic molecules activation to the corresponding radicals is implemented for substrates featuring relatively acidic X-H bonds and those that are characterized by low bond dissociation energy, such as C-H bond next to the heteroelements. On the other hand, reductively quenched g-CN carrying hydrogen atom reduces a carbonyl compound to the ketyl radical via PCET that is thermodynamically more favorable pathway compared to the electron transfer. The scope of these reactions is represented by cyclodimerization of α,β-unsaturated ketones to cyclopentanoles.
g-CN excited state demonstrates complex dynamics with the initial formation of singlet excited state, which upon intersystem crossing produces triplet excited state that is characterized by the lifetime > 2 μs. Due to long lifetime, g-CN activate organic molecules via EnT. For example, g-CN sensitizes singlet oxygen, which is the key intermediate in the dehydrogenation of aldoximes to nitrileoxides. The transient nitrileoxide undergoes [3+2]-cycloaddition to nitriles and gives oxadiazoles-1,2,4.
PET, ES-PCET and EnT are fundamental phenomena that are applied beyond organic photocatalysis. Hybrid composite is formed by combining conductive polymers, such as poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS) with potassium poly(heptazine imide) (K-PHI). Upon PET, K-PHI modulated population of polarons and therefore conductivity of PEDOT:PSS. The initial state of PEDOT:PSS is recovered upon material exposure to O2. K-PHI:PEDOT:PSS may be applied in O2 sensing.
In the presence of electron donors, such as tertiary amines and alcohols, and irradiation with light, K-PHI undergoes photocharging – the g-CN material accumulates electrons and charge-compensating cations. Such photocharged state is stable under anaerobic conditions for weeks, but at the same time it is a strong reductant. This feature allows decoupling in time light harvesting and energy storage in the form of electron-proton couples from utilization in organic synthesis. The photocharged state of K-PHI reduces nitrobenzene to aniline, and enables dimerization of α,β-unsaturated ketones to hexadienones in dark.
Solar photocatalysis is the one of leading concepts of research in the current paradigm of sustainable chemical industry. For actual practical implementation of sunlight-driven catalytic processes in organic synthesis, a cheap, efficient, versatile and robust heterogeneous catalyst is necessary. Carbon nitrides are a class of organic semiconductors who are known to fulfill these requirements.
First, current state of solar photocatalysis in economy, industry and lab research is overviewed, outlining EU project funding, prospective synthetic and reforming bulk processes, small scale solar organic chemistry, and existing reactor designs and prototypes, concluding feasibility of the approach.
Then, the photocatalytic aerobic cleavage of oximes to corresponding aldehydes and ketones by anionic poly(heptazine imide) carbon nitride is discussed. The reaction provides a feasible method of deprotection and formation of carbonyl compounds from nitrosation products and serves as a convenient model to study chromoselectivity and photophysics of energy transfer in heterogeneous photocatalysis.
Afterwards, the ability of mesoporous graphitic carbon nitride to conduct proton-coupled electron transfer was utilized for the direct oxygenation of 1,3-oxazolidin-2-ones to corresponding 1,3-oxazlidine-2,4-diones. This reaction provides an easier access to a key scaffold of diverse types of drugs and agrochemicals.
Finally, a series of novel carbon nitrides based on poly(triazine imide) and poly(heptazine imide) structure was synthesized from cyanamide and potassium rhodizonate. These catalysts demonstrated a good performance in a set of photocatalytic benchmark reactions, including aerobic oxidation, dual nickel photoredox catalysis, hydrogen peroxide evolution and chromoselective transformation of organosulfur precursors.
Concluding, the scope of carbon nitride utilization for net-oxidative and net-neutral photocatalytic processes was expanded, and a new tunable platform for catalyst synthesis was discovered.
Biogeochemical analyses of lacustrine environments are well-established methods that allow exploring and understanding complex systems in the lake ecosystem. However, most were conducted in temperate lakes controlled by entirely different physical conditions than in tropical climates. The most important difference between the temperate and tropical lakes is lacking seasonal temperature fluctuations in the latter, which leads to a stable temperature gradient in the water column. Thus, the water column in tropical latitudes generally is void of perturbations that can be seen in their temperate counterparts. Permanent stratification in the water column provides optimal conditions for intact sedimentation. The geochemical processes in the water column and the weathering process in the distinct lithology in the catchment leads to the different biogeochemical characteristic in the sediment. Conducting a biogeochemical study in this lake sediment, especially in the Sediment Water Interface (SWI) helps reveal the sedimentation and diagenetic process records influenced by the internal or external loading. Lake Sentani, the study area, is one of the thousands of lakes in Indonesia and located in the Papua province. This tropical lake has a unique feature, as it consists of four interconnected sub-basins with different water depths. More importantly, its catchment is comprised of various different lithologies. Hence, its lithological characteristics are highly diverse, and range from mafic and ultramafic rocks to clastic sediment and carbonates. Each sub-basin receives a distinct sediment input. Equally important, besides the natural loading, Lake Sentani is also influenced by anthropogenic input. Previous studies have elaborated that there is an increase in population growth rate around the lake which has direct consequences on eutrophication. Considering these factors, the government of The Republic of Indonesia put Lake Sentani on the list of national priority lakes for restoration. This thesis aims to develop a fundamental understanding of Lake Sentani's sedimentary geochemistry and geomicrobiology with a special focus on the effects of different lithologies and anthropogenic pressures in the catchment area. We conducted geochemical and geomicrobiology research on Lake Sentani to meet this objective. We investigated geochemical characteristics in the water column, porewater, and sediment core of the four sub-basins. Additional to direct investigations of the lake itself, we also studied the sediments in the tributary rivers, of which some are ephemeral, as well as the river mouths, as connections between riverine and the lacustrine habitat. The thesis is composed of three main publications about Lake Sentani and supported by several publications that focus on other tropical lakes in Indonesia. The first main publication investigates the geochemical characterization of the water column, porewater, and surface sediment (upper 40-50 cm) from the center of the four sub-basins. It reveals that besides catchment lithology, the water column heavily influences the geochemical characteristics in the lake sediments and their porewater. The findings indicate that water column stratification has a strong influence on overall chemistry. The four sub-basins are very different with regard to their water column chemistry. Based on the physicochemical profiles, especially dissolved oxygen, one sub-basin is oxygenated, one intermediate i.e. just reaches oxygen depletion at the sediment-water interface, and two sub-basins are fully meromictic. However, all four sub-basins share the same surface water chemistry. The structure of the water column creates differences on the patterns of anions and cations in the porewater. Likewise, the distinct differences in geochemical composition between the sub-basins show that the lithology in the catchment affects the geochemical characteristic in the sediment. Overall, water column stratification and particularly bottom water oxygenation strongly influence the overall elemental composition of the sediment and porewater composition. The second publication reveals differences in surface sediment composition between habitats, influenced by lithological variations in the catchment area. The macro-element distribution shows that the geochemical characteristics between habitats are different. Furthermore, the geochemical composition also indicates a distinct distribution between the sub-basins. The geochemical composition of the eastern sub-basin suggests that lithogenic elements are more dominant than authigenic elements. This is also supported by sulfide speciation, particle distribution, and smear slide data. The third publication is a geomicrobiological study of the surface sediment. We compare the geochemical composition of the surface sediment and its microbiological composition and compare the different signals. Next Generation Sequencing (NGS) of the 16S rRNA gene was applied to determine the microbial community composition of the surface sediment from a great number of locations. We use a large number of sampling sites in all four sub-basins as well as in the rivers and river mouths to illustrate the links between the river, the river mouth, and the lake. Rigorous assessment of microbial communities across the diverse Lake Sentani habitats allowed us to study some of these links and report novel findings on microbial patterns in such ecosystems. The main result of the Principal Coordinates Analysis (PCoA) based on microbial community composition highlighted some commonalities but also differences between the microbial community analysis and the geochemical data. The microbial community in rivers, river mouths and sub-basins is strongly influenced by anthropogenic input from the catchment area. Generally, Bacteroidetes and Firmicutes could be an indicator for river sediments. The microbial community in the river is directly influenced by anthropogenic pressure and is markedly different from the lake sediment. Meanwhile, the microbial community in the lake sediment reflects the anoxic environment, which is prevalent across the lake in all sediments below a few mm burial depth. The lake sediments harbour abundant sulfate reducers and methanogens. The microbial communities in sediments from river mouths are influenced by both rivers and lake ecosystems. This study provides valuable information to understand the basic processes that control biogeochemical cycling in Lake Sentani. Our findings are critical for lake managers to accurately assess the uncertainties of the changing environmental conditions related to the anthropogenic pressure in the catchment area. Lake Sentani is a unique study site directly influenced by the different geology across the watershed and morphometry of the four studied basins. As a result of these factors, there are distinct geochemical differences between the habitats (river, river mouth, lake) and the four sub-basins. In addition to geochemistry, microbial community composition also shows differences between habitats, although there are no obvious differences between the four sub-basins. However, unlike sediment geochemistry, microbial community composition is impacted by human activities. Therefore, this thesis will provide crucial baseline data for future lake management.
The shallow Earth’s layers are at the interplay of many physical processes: some being driven by atmospheric forcing (precipitation, temperature...) whereas others take their origins at depth, for instance ground shaking due to seismic activity. These forcings cause the subsurface to continuously change its mechanical properties, therefore modulating the strength of the surface geomaterials and hydrological fluxes. Because our societies settle and rely on the layers hosting these time-dependent properties, constraining the hydro-mechanical dynamics of the shallow subsurface is crucial for our future geographical development. One way to investigate the ever-changing physical changes occurring under our feet is through the inference of seismic velocity changes from ambient noise, a technique called seismic interferometry. In this dissertation, I use this method to monitor the evolution of groundwater storage and damage induced by earthquakes. Two research lines are investigated that comprise the key controls of groundwater recharge in steep landscapes and the predictability and duration of the transient physical properties due to earthquake ground shaking. These two types of dynamics modulate each other and influence the velocity changes in ways that are challenging to disentangle. A part of my doctoral research also addresses this interaction. Seismic data from a range of field settings spanning several climatic conditions (wet to arid climate) in various seismic-prone areas are considered. I constrain the obtained seismic velocity time-series using simple physical models, independent dataset, geophysical tools and nonlinear analysis. Additionally, a methodological development is proposed to improve the time-resolution of passive seismic monitoring.