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The genesis of chronic pain is explained by a biopsychosocial model. It hypothesizes an interdependency between environmental and genetic factors provoking aberrant long-term changes in biological and psychological regulatory systems. Physiological effects of psychological and physical stressors may play a crucial role in these maladaptive processes. Specifically, long-term demands on the stress response system may moderate central pain processing and influence descending serotonergic and noradrenergic signals from the brainstem, regulating nociceptive processing at the spinal level. However, the underlying mechanisms of this pathophysiological interplay still remain unclear. This paper aims to shed light on possible pathways between physical (exercise) and psychological stress and the potential neurobiological consequences in the genesis and treatment of chronic pain, highlighting evolving concepts and promising research directions in the treatment of chronic pain. Two treatment forms (exercise and mindfulness-based stress reduction as exemplary therapies), their interaction, and the dose-response will be discussed in more detail, which might pave the way to a better understanding of alterations in the pain matrix and help to develop future prevention and therapeutic concepts
Background Low back pain (LBP) is a common pain syndrome in athletes, responsible for 28% of missed training days/year. Psychosocial factors contribute to chronic pain development. This study aims to investigate the transferability of psychosocial screening tools developed in the general population to athletes and to define athlete-specific thresholds.
Methods Data from a prospective multicentre study on LBP were collected at baseline and 1-year follow-up (n=52 athletes, n=289 recreational athletes and n=246 non-athletes). Pain was assessed using the Chronic Pain Grade questionnaire. The psychosocial Risk Stratification Index (RSI) was used to obtain prognostic information regarding the risk of chronic LBP (CLBP). Individual psychosocial risk profile was gained with the Risk Prevention Index – Social (RPI-S). Differences between groups were calculated using general linear models and planned contrasts. Discrimination thresholds for athletes were defined with receiver operating characteristics (ROC) curves.
Results Athletes and recreational athletes showed significantly lower psychosocial risk profiles and prognostic risk for CLBP than non-athletes. ROC curves suggested discrimination thresholds for athletes were different compared with non-athletes. Both screenings demonstrated very good sensitivity (RSI=100%; RPI-S: 75%–100%) and specificity (RSI: 76%–93%; RPI-S: 71%–93%). RSI revealed two risk classes for pain intensity (area under the curve (AUC) 0.92(95% CI 0.85 to 1.0)) and pain disability (AUC 0.88(95% CI 0.71 to 1.0)).
Conclusions Both screening tools can be used for athletes. Athlete-specific thresholds will improve physicians’ decision making and allow stratified treatment and prevention.
German football stadiums are well known for their atmosphere. It is often described as ‘electrifying,’ or ‘cracking.’ This article focuses on this atmosphere. Using a phenomenological approach, it explores how this emotionality can be understood and how geography matters while attending a match. Atmosphere in this context is conceptualized based on work by as a mood-charged space, neither object- nor subject-centered, but rather a medium of perception which cannot not exist. Based on qualitative research done in the home stadium of Hertha BSC in the German Bundesliga, this article shows that the bodily sensations experienced by spectators during a visit to the stadium are synchronized with events on the pitch and with the more or less imposing scenery. The analysis of in situ diaries reveals that spectators experience a comprehensive sense of collectivity. The study presents evidence that the occurrence of these bodily sensations is strongly connected with different aspects of spatiality. This includes sensations of constriction and expansion within the body, an awareness of one’s location within the stadium, the influence of the immediate surroundings and cognitive here/there and inside/outside distinctions.
Epigenetic modifications, of which DNA methylation is the most stable, are a mechanism conveying environmental information to subsequent generations via parental germ lines. The paternal contribution to adaptive processes in the offspring might be crucial, but has been widely neglected in comparison to the maternal one. To address the paternal impact on the offspring's adaptability to changes in diet composition, we investigated if low protein diet (LPD) in F0 males caused epigenetic alterations in their subsequently sired sons. We therefore fed F0 male Wild guinea pigs with a diet lowered in protein content (LPD) and investigated DNA methylation in sons sired before and after their father's LPD treatment in both, liver and testis tissues. Our results point to a 'heritable epigenetic response' of the sons to the fathers' dietary change. Because we detected methylation changes also in the testis tissue, they are likely to be transmitted to the F2 generation. Gene-network analyses of differentially methylated genes in liver identified main metabolic pathways indicating a metabolic reprogramming ('metabolic shift'). Epigenetic mechanisms, allowing an immediate and inherited adaptation may thus be important for the survival of species in the context of a persistently changing environment, such as climate change.
Quantifying rock weakening due to decreasing calcite mineral content by numerical simulations
(2018)
The quantification of changes in geomechanical properties due to chemical reactions is of paramount importance for geological subsurface utilisation, since mineral dissolution generally reduces rock stiffness. In the present study, the effective elastic moduli of two digital rock samples, the Fontainebleau and Bentheim sandstones, are numerically determined based on micro-CT images. Reduction in rock stiffness due to the dissolution of 10% calcite cement by volume out of the pore network is quantified for three synthetic spatial calcite distributions (coating, partial filling and random) using representative sub-cubes derived from the digital rock samples. Due to the reduced calcite content, bulk and shear moduli decrease by 34% and 38% in maximum, respectively. Total porosity is clearly the dominant parameter, while spatial calcite distribution has a minor impact, except for a randomly chosen cement distribution within the pore network. Moreover, applying an initial stiffness reduced by 47% for the calcite cement results only in a slightly weaker mechanical behaviour. Using the quantitative approach introduced here substantially improves the accuracy of predictions in elastic rock properties compared to general analytical methods, and further enables quantification of uncertainties related to spatial variations in porosity and mineral distribution.
Hyenas (family Hyaenidae), as the sister group to cats (family Felidae), represent a deeply diverging branch within the cat-like carnivores (Feliformia). With an estimated population size of <10,000 individuals worldwide, the brown hyena (Parahyaena brunnea) represents the rarest of the four extant hyena species and has been listed as Near Threatened by the IUCN. Here, we report a high-coverage genome from a captive bred brown hyena and both mitochondrial and low-coverage nuclear genomes of 14 wild-caught brown hyena individuals from across southern Africa. We find that brown hyena harbor extremely low genetic diversity on both the mitochondrial and nuclear level, most likely resulting from a continuous and ongoing decline in effective population size that started similar to 1 Ma and dramatically accelerated towards the end of the Pleistocene. Despite the strikingly low genetic diversity, we find no evidence of inbreeding within the captive bred individual and reveal phylogeographic structure, suggesting the existence of several potential subpopulations within the species.
The sequencing of the human genome in the early 2000s led to an increased interest in cheap and fast sequencing technologies. This interest culminated in the advent of next generation sequencing (NGS). A number of different NGS platforms have arisen since then all promising to do the same thing, i.e. produce large amounts of genetic information for relatively low costs compared to more traditional methods such as Sanger sequencing. The capabilities of NGS meant that researchers were no longer bound to species for which a lot of previous work had already been done (e.g. model organisms and humans) enabling a shift in research towards more novel and diverse species of interest. This capability has greatly benefitted many fields within the biological sciences, one of which being the field of evolutionary biology. Researchers have begun to move away from the study of laboratory model organisms to wild, natural populations and species which has greatly expanded our knowledge of evolution. NGS boasts a number of benefits over more traditional sequencing approaches. The main benefit comes from the capability to generate information for drastically more loci for a fraction of the cost. This is hugely beneficial to the study of wild animals as, even when large numbers of individuals are unobtainable, the amount of data produced still allows for accurate, reliable population and species level results from a small selection of individuals.
The use of NGS to study species for which little to no previous research has been carried out on and the production of novel evolutionary information and reference datasets for the greater scientific community were the focuses of this thesis. Two studies in this thesis focused on producing novel mitochondrial genomes from shotgun sequencing data through iterative mapping, bypassing the need for a close relative to serve as a reference sequence. These mitochondrial genomes were then used to infer species level relationships through phylogenetic analyses. The first of these studies involved reconstructing a complete mitochondrial genome of the bat eared fox (Otocyon megalotis). Phylogenetic analyses of the mitochondrial genome confidently placed the bat eared fox as sister to the clade consisting of the raccoon dog and true foxes within the canidae family. The next study also involved reconstructing a mitochondrial genome but in this case from the extinct Macrauchenia of South America. As this study utilised ancient DNA, it involved a lot of parameter testing, quality controls and strict thresholds to obtain a near complete mitochondrial genome devoid of contamination known to plague ancient DNA studies. Phylogenetic analyses confidently placed Macrauchenia as sister to all living representatives of Perissodactyla with a divergence time of ~66 million years ago. The third and final study of this thesis involved de novo assemblies of both nuclear and mitochondrial genomes from brown and striped hyena and focussed on demographic, genetic diversity and population genomic analyses within the brown hyena. Previous studies of the brown hyena hinted at very low levels of genomic diversity and, perhaps due to this, were unable to find any notable population structure across its range. By incorporating a large number of genetic loci, in the form of complete nuclear genomes, population structure within the brown hyena was uncovered. On top of this, genomic diversity levels were compared to a number of other species. Results showed the brown hyena to have the lowest genomic diversity out of all species included in the study which was perhaps caused by a continuous and ongoing decline in effective population size that started about one million years ago and dramatically accelerated towards the end of the Pleistocene.
The studies within this thesis show the power NGS sequencing has and its utility within evolutionary biology. The most notable capabilities outlined in this thesis involve the study of species for which no reference data is available and in the production of large amounts of data, providing evolutionary answers at the species and population level that data produced using more traditional techniques simply could not.
Moving arms
(2018)
Embodied cognition postulates a bi-directional link between the human body and its cognitive functions. Whether this holds for higher cognitive functions such as problem solving is unknown. We predicted that arm movement manipulations performed by the participants could affect the problem-solving solutions. We tested this prediction in quantitative reasoning tasks that allowed two solutions to each problem (addition or subtraction). In two studies with healthy adults (N=53 and N=50), we found an effect of problem-congruent movements on problem solutions. Consistent with embodied cognition, sensorimotor information gained via right or left arm movements affects the solution in different types of problem-solving tasks.
This paper introduces a novel measure to assess similarity between event hydrographs. It is based on Cross Recurrence Plots and Recurrence Quantification Analysis which have recently gained attention in a range of disciplines when dealing with complex systems. The method attempts to quantify the event runoff dynamics and is based on the time delay embedded phase space representation of discharge hydrographs. A phase space trajectory is reconstructed from the event hydrograph, and pairs of hydrographs are compared to each other based on the distance of their phase space trajectories. Time delay embedding allows considering the multi-dimensional relationships between different points in time within the event. Hence, the temporal succession of discharge values is taken into account, such as the impact of the initial conditions on the runoff event. We provide an introduction to Cross Recurrence Plots and discuss their parameterization. An application example based on flood time series demonstrates how the method can be used to measure the similarity or dissimilarity of events, and how it can be used to detect events with rare runoff dynamics. It is argued that this methods provides a more comprehensive approach to quantify hydrograph similarity compared to conventional hydrological signatures.
Three Essays on EFRAG
(2018)
This cumulative doctoral thesis consists of three papers that deal with the role of one specific European accounting player in the international accounting standard-setting, namely the European Financial Reporting Advisory Group (EFRAG). The first paper examines whether and how EFRAG generally fulfills its role in articulating Europe’s interests toward the International Accounting Standards Board (IASB). The qualitative data from the conducted interviews reveal that EFRAG influences the IASB’s decision making at a very early stage, long before other constituents are officially asked to comment on the IASB’s proposals. The second paper uses quantitative data and investigates the formal participation behavior of European constituents that seek to determine EFRAG’s voice. More precisely, this paper analyzes the nature of the constituents’ participation in EFRAG’s due process in terms of representation (constituent groups and geographical distribution) and the drivers of their participation behavior. EFRAG’s official decision making process is dominated by some specific constituent groups (such as preparers and the accounting profession) and by constituents from some specific countries (e.g. those with effective enforcement regimes). The third paper investigates in a first step who of the European constituents choose which lobbying channel (participation only at IASB, only at EFRAG, or at both institutions) and unveils in a second step possible reasons for their lobbying choices. The paper comprises quantitative and qualitative data. It reveals that English skills, time issues, the size of the constituent, and the country of origin are factors that can explain why the majority participates only in the IASB’s due process.
Symptoms of anxiety and depression in young athletes using the Hospital Anxiety and Depression Scale
(2018)
Elite young athletes have to cope with multiple psychological demands such as training volume, mental and physical fatigue, spatial separation of family and friends or time management problems may lead to reduced mental and physical recovery. While normative data regarding symptoms of anxiety and depression for the general population is available (Hinz and Brahler, 2011), hardly any information exists for adolescents in general and young athletes in particular. Therefore, the aim of this study was to assess overall symptoms of anxiety and depression in young athletes as well as possible sex differences. The survey was carried out within the scope of the study "Resistance Training in Young Athletes" (KINGS-Study). Between August 2015 and September 2016, 326 young athletes aged (mean +/- SD) 14.3 +/- 1.6 years completed the Hospital Anxiety and Depression Scale (HAD Scale). Regarding the analysis of age on the anxiety and depression subscales, age groups were classified as follows: late childhood (12-14 years) and late adolescence (15-18 years). The participating young athletes were recruited from Olympic weight lifting, handball, judo, track and field athletics, boxing, soccer, gymnastics, ice speed skating, volleyball, and rowing. Anxiety and depression scores were (mean +/- SD) 4.3 +/- 3.0 and 2.8 +/- 2.9, respectively. In the subscale anxiety, 22 cases (6.7%) showed subclinical scores and 11 cases (3.4%) showed clinical relevant score values. When analyzing the depression subscale, 31 cases (9.5%) showed subclinical score values and 12 cases (3.7%) showed clinically important values. No significant differences were found between male and female athletes (p >= 0.05). No statistically significant differences in the HADS scores were found between male athletes of late childhood and late adolescents (p >= 0.05). To the best of our knowledge, this is the first report describing questionnaire based indicators of symptoms of anxiety and depression in young athletes. Our data implies the need for sports medical as well as sports psychiatric support for young athletes. In addition, our results demonstrated that the chronological classification concerning age did not influence HAD Scale outcomes. Future research should focus on sports medical and sports psychiatric interventional approaches with the goal to prevent anxiety and depression as well as teaching coping strategies to young athletes.
Background/Aims: Angiogenesis plays a key role during embryonic development. The vascular endothelin (ET) system is involved in the regulation of angiogenesis. Lipopolysaccharides (LPS) could induce angiogenesis. The effects of ET blockers on baseline and LPS-stimulated angiogenesis during embryonic development remain unknown so far. Methods: The blood vessel density (BVD) of chorioallantoic membranes (CAMs), which were treated with saline (control), LPS, and/or BQ123 and the ETB blocker BQ788, were quantified and analyzed using an IPP 6.0 image analysis program. Moreover, the expressions of ET-1, ET-2, ET3, ET receptor A (ETRA), ET receptor B (ETRB) and VEGFR2 mRNA during embryogenesis were analyzed by semi-quantitative RT-PCR. Results: All components of the ET system are detectable during chicken embryogenesis. LPS increased angiogenesis substantially. This process was completely blocked by the treatment of a combination of the ETA receptor blockers-BQ123 and the ETB receptor blocker BQ788. This effect was accompanied by a decrease in ETRA, ETRB, and VEGFR2 gene expression. However, the baseline angiogenesis was not affected by combined ETA/ETB receptor blockade. Conclusion: During chicken embryogenesis, the LPS-stimulated angiogenesis, but not baseline angiogenesis, is sensitive to combined ETA/ETB receptor blockade. (C) 2018 The Author(s) Published by S. Karger AG, Basel
High-latitude treeless ecosystems represent spatially highly heterogeneous landscapes with small net carbon fluxes and a short growing season. Reliable observations and process understanding are critical for projections of the carbon balance of the climate-sensitive tundra. Space-borne remote sensing is the only tool to obtain spatially continuous and temporally resolved information on vegetation greenness and activity in remote circumpolar areas. However, confounding effects from persistent clouds, low sun elevation angles, numerous lakes, widespread surface inundation, and the sparseness of the vegetation render it highly challenging. Here, we conduct an extensive analysis of the timing of peak vegetation productivity as shown by satellite observations of complementary indicators of plant greenness and photosynthesis. We choose to focus on productivity during the peak of the growing season, as it importantly affects the total annual carbon uptake. The suite of indicators are as follows: (1) MODIS-based vegetation indices (VIs) as proxies for the fraction of incident photosynthetically active radiation (PAR) that is absorbed (fPAR), (2) VIs combined with estimates of PAR as a proxy of the total absorbed radiation (APAR), (3) sun-induced chlorophyll fluorescence (SIF) serving as a proxy for photosynthesis, (4) vegetation optical depth (VOD), indicative of total water content and (5) empirically upscaled modelled gross primary productivity (GPP). Averaged over the pan-Arctic we find a clear order of the annual peak as APAR ≦ GPP<SIF<VIs/VOD. SIF as an indicator of photosynthesis is maximised around the time of highest annual temperatures. The modelled GPP peaks at a similar time to APAR. The time lag of the annual peak between APAR and instantaneous SIF fluxes indicates that the SIF data do contain information on light-use efficiency of tundra vegetation, but further detailed studies are necessary to verify this. Delayed peak greenness compared to peak photosynthesis is consistently found across years and land-cover classes. A particularly late peak of the normalised difference vegetation index (NDVI) in regions with very small seasonality in greenness and a high amount of lakes probably originates from artefacts. Given the very short growing season in circumpolar areas, the average time difference in maximum annual photosynthetic activity and greenness or growth of 3 to 25 days (depending on the data sets chosen) is important and needs to be considered when using satellite observations as drivers in vegetation models.
This essay sets out to theorize the “new” Arctic Ocean as a pivot from
which our standard map of the world is currently being
reconceptualized. Drawing on theories from the fields of Atlantic
and Pacific studies, I argue that the changing Arctic, characterized
by melting ice and increased accessibility, must be understood
both as a space of transit that connects Atlantic and Pacific worlds
in unprecedented ways, and as an oceanic world and contact
zone in its own right. I examine both functions of the Arctic via a
reading of the dispute over the Northwest Passage (which
emphasizes the Arctic as a space of transit) and the contemporary
assessment of new models of sovereignty in the Arctic region
(which concentrates on the circumpolar Arctic as an oceanic
world). However, both of these debates frequently exclude
indigenous positions on the Arctic. By reading Canadian Inuit
theories on the Arctic alongside the more prominent debates, I
argue for a decolonizing reading of the Arctic inspired by Inuit
articulations of the “Inuit Sea.” In such a reading, Inuit conceptions
provide crucial interventions into theorizing the Arctic. They also,
in turn, contribute to discussions on indigeneity, sovereignty, and
archipelagic theory in Atlantic and Pacific studies.
Hatred directed at members of groups due to their origin, race, gender, religion, or sexual orientation is not new, but it has taken on a new dimension in the online world. To date, very little is known about online hate among adolescents. It is also unknown how online disinhibition might influence the association between being bystanders and being perpetrators of online hate. Thus, the present study focused on examining the associations among being bystanders of online hate, being perpetrators of online hate, and the moderating role of toxic online disinhibition in the relationship between being bystanders and perpetrators of online hate. In total, 1480 students aged between 12 and 17 years old were included in this study. Results revealed positive associations between being online hate bystanders and perpetrators, regardless of whether adolescents had or had not been victims of online hate themselves. The results also showed an association between toxic online disinhibition and online hate perpetration. Further, toxic online disinhibition moderated the relationship between being bystanders of online hate and being perpetrators of online hate. Implications for prevention programs and future research are discussed.
Although school climate and self-efficacy have received some attention in the literature, as correlates of students’ willingness to intervene in bullying, to date, very little is known about the potential mediating role of self-efficacy in the relationship between classroom climate and students’ willingness to intervene in bullying. To this end, the present study analyzes whether the relationship between classroom cohesion (as one facet of classroom climate) and students’ willingness to intervene in bullying situations is mediated by self-efficacy in social conflicts. This study is based on a representative stratified random sample of two thousand and seventy-one students (51.3% male), between the ages of twelve and seventeen, from twenty-four schools in Germany. Results showed that between 43% and 48% of students reported that they would not intervene in bullying. A mediation test using the structural equation modeling framework revealed that classroom cohesion and self-efficacy in social conflicts were directly associated with students’ willingness to intervene in bullying situations. Furthermore, classroom cohesion was indirectly associated with higher levels of students’ willingness to intervene in bullying situations, due to self-efficacy in social conflicts. We thus conclude that: (1) It is crucial to increase students’ willingness to intervene in bullying; (2) efforts to increase students’ willingness to intervene in bullying should promote students’ confidence in dealing with social conflicts and interpersonal relationships; and (3) self-efficacy plays an important role in understanding the relationship between classroom cohesion and students’ willingness to intervene in bullying. Recommendations are provided to help increase adolescents’ willingness to intervene in bullying and for future research.
This paper investigates the transferability of calibrated HBV model parameters under stable and contrasting conditions in terms of flood seasonality and flood generating processes (FGP) in five Norwegian catchments with mixed snowmelt/rainfall regimes. We apply a series of generalized (differential) split-sample tests using a 6-year moving window over (i) the entire runoff observation periods, and (ii) two subsets of runoff observations distinguished by the seasonal occurrence of annual maximum floods during either spring or autumn. The results indicate a general model performance loss due to the transfer of calibrated parameters to independent validation periods of −5 to −17%, on average. However, there is no indication that contrasting flood seasonality exacerbates performance losses, which contradicts the assumption that optimized parameter sets for snowmelt-dominated floods (during spring) perform particularly poorly on validation periods with rainfall-dominated floods (during autumn) and vice versa.
Poly(vinylidene fluoride-trifluoroethylene) (P(VDF-TrFE)) ferroelectric thin films of different molar ratio have been studied with regard to data memory applications. Therefore, films with thicknesses of 200 nm and less have been spin coated from solution. Observations gained from single layers have been extended to multilayer capacitors and three terminal transistor devices.
Besides conventional hysteresis measurements, the measurement of dielectric non-linearities has been used as a main tool of characterisation. Being a very sensitive and non-destructive method, non-linearity measurements are well suited for polarisation readout and property studies. Samples have been excited using a high quality, single-frequency sinusoidal voltage with an amplitude significantly smaller than the coercive field of the samples. The response was then measured at the excitation frequency and its higher harmonics. Using the measurement results, the linear and non-linear dielectric permittivities ɛ₁, ɛ₂ and ɛ₃ have been determined. The permittivities have been used to derive the temperature-dependent polarisation behaviour as well as the polarisation state and the order of the phase transitions.
The coercive field in VDF-TrFE copolymers is high if compared to their ceramic competitors. Therefore, the film thickness had to be reduced significantly. Considering a switching voltage of 5 V and a coercive field of 50 MV/m, the film thickness has to be 100 nm and below. If the thickness becomes substantially smaller than the other dimensions, surface and interface layer effects become more pronounced. For thicker films of P(VDF-TrFE) with a molar fraction of 56/44 a second-order phase transition without a thermal hysteresis for an ɛ₁(T) temperature cycle has been predicted and observed. This however, could not be confirmed by the measurements of thinner films. A shift of transition temperatures as well as a temperature independent, non-switchable polarisation and a thermal hysteresis for P(VDF-TrFE) 56/44 have been observed. The impact of static electric fields on the polarisation and the phase transition has therefore been studied and simulated, showing that all aforementioned phenomena including a linear temperature dependence of the polarisation might originate from intrinsic electric fields.
In further experiments the knowledge gained from single layer capacitors has been extended to bilayer copolymer thin films of different molar composition. Bilayers have been deposited by succeeding cycles of spin coating from solution. Single layers and their bilayer combination have been studied individually in order to prove the layers stability. The individual layers have been found to be physically stable. But while the bilayers reproduced the main ɛ₁(T) properties of the single layers qualitatively, quantitative numbers could not be explained by a simple serial connection of capacitors. Furthermore, a linear behaviour of the polarisation throughout the measured temperature range has been observed. This was found to match the behaviour predicted considering a constant electric field.
Retention time is an important quantity for memory applications. Hence, the retention behaviour of VDF-TrFE copolymer thin films has been determined using dielectric non-linearities. The polarisation loss in P(VDF-TrFE) poled samples has been found to be less than 20% if recorded over several days. The loss increases significantly if the samples have been poled with lower amplitudes, causing an unsaturated polarisation. The main loss was attributed to injected charges. Additionally, measurements of dielectric non-linearities have been proven to be a sensitive and non-destructive tool to measure the retention behaviour.
Finally, a ferroelectric field effect transistor using mainly organic materials (FerrOFET) has been successfully studied. DiNaphtho[2,3-b:2',3'-f]Thieno[3,2-b]Thiophene (DNTT) has proven to be a stable, suitable organic semiconductor to build up ferroelectric memory devices. Furthermore, an oxidised aluminium bottom electrode and additional dielectric layers, i.e. parylene C, have proven to reduce the leakage current and therefore enhance the performance significantly.
The development of self-adaptive software requires the engineering of an adaptation engine that controls the underlying adaptable software by a feedback loop. State-of-the-art approaches prescribe the feedback loop in terms of numbers, how the activities (e.g., monitor, analyze, plan, and execute (MAPE)) and the knowledge are structured to a feedback loop, and the type of knowledge. Moreover, the feedback loop is usually hidden in the implementation or framework and therefore not visible in the architectural design. Additionally, an adaptation engine often employs runtime models that either represent the adaptable software or capture strategic knowledge such as reconfiguration strategies. State-of-the-art approaches do not systematically address the interplay of such runtime models, which would otherwise allow developers to freely design the entire feedback loop.
This thesis presents ExecUtable RuntimE MegAmodels (EUREMA), an integrated model-driven engineering (MDE) solution that rigorously uses models for engineering feedback loops. EUREMA provides a domain-specific modeling language to specify and an interpreter to execute feedback loops. The language allows developers to freely design a feedback loop concerning the activities and runtime models (knowledge) as well as the number of feedback loops. It further supports structuring the feedback loops in the adaptation engine that follows a layered architectural style. Thus, EUREMA makes the feedback loops explicit in the design and enables developers to reason about design decisions.
To address the interplay of runtime models, we propose the concept of a runtime megamodel, which is a runtime model that contains other runtime models as well as activities (e.g., MAPE) working on the contained models. This concept is the underlying principle of EUREMA. The resulting EUREMA (mega)models are kept alive at runtime and they are directly executed by the EUREMA interpreter to run the feedback loops. Interpretation provides the flexibility to dynamically adapt a feedback loop. In this context, EUREMA supports engineering self-adaptive software in which feedback loops run independently or in a coordinated fashion within the same layer as well as on top of each other in different layers of the adaptation engine. Moreover, we consider preliminary means to evolve self-adaptive software by providing a maintenance interface to the adaptation engine.
This thesis discusses in detail EUREMA by applying it to different scenarios such as single, multiple, and stacked feedback loops for self-repairing and self-optimizing the mRUBiS application. Moreover, it investigates the design and expressiveness of EUREMA, reports on experiments with a running system (mRUBiS) and with alternative solutions, and assesses EUREMA with respect to quality attributes such as performance and scalability.
The conducted evaluation provides evidence that EUREMA as an integrated and open MDE approach for engineering self-adaptive software seamlessly integrates the development and runtime environments using the same formalism to specify and execute feedback loops, supports the dynamic adaptation of feedback loops in layered architectures, and achieves an efficient execution of feedback loops by leveraging incrementality.
Deoxyribonucleic acid (DNA) is the carrier of human genetic information and is exposed to environmental influences such as the ultraviolet (UV) fraction of sunlight every day. The photostability of the DNA against UV light is astonishing. Even if the DNA bases have a strong absorption maximum at around 260 nm/4.77 eV, their quantum yield of photoproducts remains very low 1. If the photon energies exceed the ionization energy (IE) of the nucleobases ( ̴ 8-9 eV) 2, the DNA can be severely damaged. Photoexcitation and -ionization reactions occur, which can induce strand breaks in the DNA. The efficiency of the excitation and ionization induced strand breaks in the target DNA sequences are represented by cross sections. If Si as a substrate material is used in the VUV irradiation experiments, secondary electrons with an energy below 3.6 eV are generated from the substrate. This low energy electrons (LEE) are known to induce dissociative electron attachment (DEA) in DNA and with it DNA strand breakage very efficiently. LEEs play an important role in cancer radiation therapy, since they are generated secondarily along the radiation track of ionizing radiation.
In the framework of this thesis, different single stranded DNA sequences were irradiated with 8.44 eV vacuum UV (VUV) light and cross sections for single strand breaks (SSB) were determined. Several sequences were also exposed to secondary LEEs, which additionally contributed to the SSBs. First, the cross sections for SSBs depending on the type of nucleobases were determined. Both types of DNA sequences, mono-nucleobase and mixed sequences showed very similar results upon VUV radiation. The additional influence of secondarily generated LEEs resulted in contrast in a clear trend for the SSB cross sections. In this, the polythymine sequence had the highest cross section for SSBs, which can be explained by strong anionic resonances in this energy range. Furthermore, SSB cross sections were determined as a function of sequence length. This resulted in an increase in the strand breaks to the same extent as the increase in the geometrical cross section. The longest DNA sequence (20 nucleotides) investigated in this series, however, showed smaller cross section values for SSBs, which can be explained by conformational changes in the DNA. Moreover, several DNA sequences that included the radiosensitizers 5-Bromouracil (5BrU) and 8-Bromoadenine (8BrA) were investigated and the corresponding SSB cross sections were determined. It was shown that 5BrU reacts very strongly to VUV radiation leading to high strand break yields, which showed in turn a strong sequence-dependency. 8BrA, on the other hand, showed no sensitization to the applied VUV radiation, since almost no increase in strand breakage yield was observed in comparison to non-modified DNA sequences.
In order to be able to identify the mechanisms of radiation damage by photons, the IEs of certain DNA sequences were further explored using photoionization tandem mass spectrometry. By varying the DNA sequence, both the IEs depending on the type of nucleobase as well as on the DNA strand length could be identified and correlated to the SSB cross sections. The influence of the IE on the photoinduced reaction in the brominated DNA sequences could be excluded.