Refine
Has Fulltext
- yes (130) (remove)
Year of publication
- 2019 (130) (remove)
Document Type
- Doctoral Thesis (130) (remove)
Is part of the Bibliography
- yes (130)
Keywords
- Klimawandel (4)
- Spektroskopie (4)
- climate change (4)
- Biodiversität (3)
- machine learning (3)
- spectroscopy (3)
- Anden (2)
- Andes (2)
- Himalaya (2)
- Klima (2)
Institute
- Institut für Biochemie und Biologie (22)
- Institut für Geowissenschaften (18)
- Institut für Physik und Astronomie (17)
- Institut für Chemie (15)
- Hasso-Plattner-Institut für Digital Engineering GmbH (10)
- Extern (9)
- Department Linguistik (8)
- Institut für Umweltwissenschaften und Geographie (6)
- Sozialwissenschaften (5)
- Institut für Mathematik (4)
Frailty and sarcopenia share some underlying characteristics like loss of muscle mass, low muscle strength, and low physical performance. Imaging parameters and functional examinations mainly assess frailty and sarcopenia criteria; however, these measures can have limitations in clinical settings. Therefore, finding suitable biomarkers that reflect a catabolic muscle state e.g. an elevated muscle protein turnover as suggested in frailty, are becoming more relevant concerning frailty diagnosis and risk assessment.
3-Methylhistidine (3-MH) and its ratios 3-MH-to-creatinine (3-MH/Crea) and 3 MH-to-estimated glomerular filtration rate (3-MH/eGFR) are under discussion as possible biomarkers for muscle protein turnover and might support the diagnosis of frailty. However, there is some skepticism about the reliability of 3-MH measures since confounders such as meat and fish intake might influence 3-MH plasma concentrations. Therefore, the influence of dietary habits and an intervention with white meat on plasma 3-MH was determined in young and healthy individuals. In another study, the cross-sectional associations of plasma 3-MH, 3-MH/Crea and 3-MH/eGFR with the frailty status (robust, pre-frail and frail) were investigated.
Oxidative stress (OS) is a possible contributor to frailty development, and high OS levels as well as low micronutrient levels are associated with the frailty syndrome. However, data on simultaneous measures of OS biomarkers together with micronutrients are lacking in studies including frail, pre-frail and robust individuals. Therefore, cross-sectional associations of protein carbonyls (PrCarb), 3-nitrotyrosine (3-NT) and several micronutrients with the frailty status were determined.
A validated UPLC-MS/MS (ultra-performance liquid chromatography tandem mass spectrometry) method for the simultaneous quantification of 3-MH and 1-MH (1 methylhistidine, as marker for meat and fish consumption) was presented and used for further analyses. Omnivores showed higher plasma 3-MH and 1-MH concentrations than vegetarians and a white meat intervention resulted in an increase in plasma 3-MH, 3 MH/Crea, 1-MH and 1-MH/Crea in omnivores. Elevated 3-MH and 3-MH/Crea levels declined significantly within 24 hours after this white meat intervention. Thus, 3-MH and 3-MH/Crea might be used as biomarker for muscle protein turnover when subjects did not consume meat 24 hours prior to blood samplings.
Plasma 3-MH, 3-MH/Crea and 3-MH/eGFR were higher in frail individuals than in robust individuals. Additionally, these biomarkers were positively associated with frailty in linear regression models, and higher odds to be frail were found for every increase in 3 MH and 3-MH/eGFR quintile in multivariable logistic regression models adjusted for several confounders. This was the first study using 3-MH/eGFR and it is concluded that plasma 3-MH, 3-MH/Crea and 3-MH/eGFR might be used to identify frail individuals or individuals at higher risk to be frail, and that there might be threshold concentrations or ratios to support these diagnoses.
Higher vitamin D3, lutein/zeaxanthin, γ-tocopherol, α-carotene, β-carotene, lycopene and β-cryptoxanthin concentrations and additionally lower PrCarb concentrations were found in robust compared to frail individuals in multivariate linear models. Frail subjects had higher odds to be in the lowest than in the highest tertile for vitamin D3 α-tocopherol, α-carotene, β-carotene, lycopene, lutein/zeaxanthin, and β cryptoxanthin, and had higher odds to be in the highest than in the lowest tertile for PrCarb than robust individuals in multivariate logistic regression models. Thus, a low micronutrient together with a high PrCarb status is associated with pre-frailty and frailty.
The increasing age of worldwide population is a major contributor for the rising prevalence of major pathologies and disease, such as type 2 diabetes, mediated by massive insulin resistance and a decline in functional beta-cell mass, highly associated with an elevated incidence of obesity. Thus, the impact of aging under physiological conditions and in combination with diet-induced metabolic stress on characteristics of pancreatic islets and beta-cells, with the focus on functionality and structural integrity, were investigated in the present dissertation.
Primarily induced by malnutrition due to chronic and excess intake of high caloric diets, containing large amounts of carbohydrates and fats, obesity followed by systemic inflammation and peripheral insulin resistance occurs over time, initiating metabolic stress conditions. Elevated insulin demands initiate an adaptive response by beta-cell mass expansion due to increased proliferation, but prolonged stress conditions drive beta-cell failure and loss. Aging has been also shown to affect beta-cell functionality and morphology, in particular by proliferative limitations. However, most studies in rodents were performed under beta-cell challenging conditions, such as high-fat diet interventions. Thus, in the first part of the thesis (publication I), a characterization of age-related alterations on pancreatic islets and beta-cells was performed by using plasma samples and pancreatic tissue sections of standard diet-fed C57BL/6J wild-type mice in several age groups (2.5, 5, 10, 15 and 21 months).
Aging was accompanied by decreased but sustained islet proliferative potential as well as an induction of cellular senescence. This was associated with a progressive islet expansion to maintain normoglycemia throughout lifespan. Moreover, beta-cell function and mass were not impaired although the formation and accumulation of AGEs occurred, located predominantly in the islet vasculature, accompanied by an induction of oxidative and nitrosative (redox) stress.
The nutritional behavior throughout human lifespan; however, is not restricted to a balanced diet. This emphasizes the significance to investigate malnutrition by the intake of high-energy diets, inducing metabolic stress conditions that synergistically with aging might amplify the detrimental effects on endocrine pancreas. Using diabetes-prone NZO mice aged 7 weeks, fed a dietary regimen of carbohydrate restriction for different periods (young mice - 11 weeks, middle-aged mice - 32 weeks) followed by a carbohydrate intervention for 3 weeks, offered the opportunity to distinguish the effects of diet-induced metabolic stress in different ages on the functionality and integrity of pancreatic islets and their beta-cells (publication II, manuscript).
Interestingly, while young NZO mice exhibited massive hyperglycemia in response to diet-induced metabolic stress accompanied by beta-cell dysfunction and apoptosis, middle-aged animals revealed only moderate hyperglycemia by the maintenance of functional beta-cells. The loss of functional beta-cell mass in islets of young mice was associated with reduced expression of PDX1 transcription factor, increased endocrine AGE formation and related redox stress as well as TXNIP-dependent induction of the mitochondrial death pathway. Although the amounts of secreted insulin and the proliferative potential were comparable in both age groups, islets of middle-aged mice exhibited sustained PDX1 expression, almost regular insulin secretory function, increased capacity for cell cycle progression as well as maintained redox potential.
The results of the present thesis indicate a loss of functional beta-cell mass in young diabetes-prone NZO mice, occurring by redox imbalance and induction of apoptotic signaling pathways. In contrast, aging under physiological conditions in C57BL/6J mice and in combination with diet-induced metabolic stress in NZO mice does not appear to have adverse effects on the functionality and structural integrity of pancreatic islets and beta-cells, associated with adaptive responses on changing metabolic demands. However, considering the detrimental effects of aging, it has to be assumed that the compensatory potential of mice might be exhausted at a later point of time, finally leading to a loss of functional beta-cell mass and the onset and progression of type 2 diabetes.
The polygenic, diabetes-prone NZO mouse is a suitable model for the investigation of human obesity-associated type 2 diabetes. However, mice at advanced age attenuated the diabetic phenotype or do not respond to the dietary stimuli. This might be explained by the middle age of mice, corresponding to the human age of about 38-40 years, in which the compensatory mechanisms of pancreatic islets and beta cells towards metabolic stress conditions are presumably more active.
Analysis of supramolecular assemblies of NE81, the first lamin protein in a non-metazoan organism
(2019)
Nuclear lamins are nucleus-specific intermediate filaments forming a network located at the inner nuclear membrane of the nuclear envelope. They form the nuclear lamina together with proteins of the inner nuclear membrane regulating nuclear shape and gene expression, among others. The amoebozoan Dictyostelium NE81 protein is a suitable candidate for an evolutionary conserved lamin protein in this non-metazoan organism. It shares the domain organization of metazoan lamins and is fulfilling major lamin functions in Dictyostelium. Moreover, field-emission scanning electron microscopy (feSEM) images of NE81 expressed on Xenopus oocytes nuclei revealed filamentous structures with an overall appearance highly reminiscent to that of metazoan Xenopus lamin B2. For the classification as a lamin-like or a bona fide lamin protein, a better understanding of the supramolecular NE81 structure was necessary. Yet, NE81 carrying a large N-terminal GFP-tag turned out as unsuitable source for protein isolation and characterization; GFP-NE81 expressed in Dictyostelium NE81 knock-out cells exhibited an abnormal distribution, which is an indicator for an inaccurate assembly of GFP-tagged NE81. Hence, a shorter 8×HisMyc construct was the tag of choice to investi-gate formation and structure of NE81 assemblies. One strategy was the structural analysis of NE81 in situ at the outer nuclear membrane in Dictyostelium cells; NE81 without a func-tional nuclear localization signal (NLS) forms assemblies at the outer face of the nucleus. Ultrastructural feSEM pictures of NE81ΔNLS nuclei showed a few filaments of the expected size but no repetitive filamentous structures. The former strategy should also be established for metazoan lamins in order to facilitate their structural analysis. However, heterologously expressed Xenopus and C. elegans lamins showed no uniform localization at the outer nucle-ar envelope of Dictyostelium and hence, no further ultrastructural analysis was undertaken. For in vitro assembly experiments a Dictyostelium mutant was generated, expressing NE81 without the NLS and the membrane-anchoring isoprenylation site (HisMyc-NE81ΔNLSΔCLIM). The cytosolic NE81 clusters were soluble at high ionic strength and were purified from Dictyostelium extracts using Ni-NTA Agarose. Widefield immunofluorescence microscopy, super-resolution light microscopy and electron microscopy images of purified NE81 showed its capability to form filamentous structures at low ionic strength, as described previously for metazoan lamins. Introduction of a phosphomimetic point mutation (S122E) into the CDK1-consensus sequence of NE81 led to disassembled NE81 protein in vivo, which could be reversibly stimulated to form supramolecular assemblies by blue light exposure.
The results of this work reveal that NE81 has to be considered a bona fide lamin, since it is able to form filamentous assemblies. Furthermore, they highlight Dictyostelium as a non-mammalian model organism with a well-characterized nuclear envelope containing all rele-vant protein components known in animal cells.
Introduction: Cystic fibrosis (CF) is a genetic disease which disrupts the function of an epithelial surface anion channel, CFTR (cystic fibrosis transmembrane conductance regulator). Impairment to this channel leads to inflammation and infection in the lung causing the majority of morbidity and mortality. However, CF is a multiorgan disease affecting many tissues, including vascular smooth muscle. Studies have revealed young people with cystic fibrosis lacking inflammation and infection still demonstrate vascular endothelial dysfunction, measured per flow-mediated dilation (FMD). In other disease cohorts, i.e. diabetic and obese, endurance exercise interventions have been shown improve or taper this impairment. However, long-term exercise interventions are risky, as well as costly in terms of time and resources. Nevertheless, emerging research has correlated the acute effects of exercise with its long-term benefits and advocates the study of acute exercise effects on FMD prior to longitudinal studies. The acute effects of exercise on FMD have previously not been examined in young people with CF, but could yield insights on the potential benefits of long-term exercise interventions.
The aims of these studies were to 1) develop and test the reliability of the FMD method and its applicability to study acute exercise effects; 2) compare baseline FMD and the acute exercise effect on FMD between young people with and without CF; and 3) explore associations between the acute effects of exercise on FMD and demographic characteristics, physical activity levels, lung function, maximal exercise capacity or inflammatory hsCRP levels.
Methods: Thirty young volunteers (10 people with CF, 10 non-CF and 10 non-CF active matched controls) between the ages of 10 and 30 years old completed blood draws, pulmonary function tests, maximal exercise capacity tests and baseline FMD measurements, before returning approximately 1 week later and performing a 30-min constant load training at 75% HRmax. FMD measurements were taken prior, immediately after, 30 minutes after and 1 hour after constant load training. ANOVAs and repeated measures ANOVAs were employed to explore differences between groups and timepoints, respectively. Linear regression was implemented and evaluated to assess correlations between FMD and demographic characteristics, physical activity levels, lung function, maximal exercise capacity or inflammatory hsCRP levels. For all comparisons, statistical significance was set at a p-value of α < 0.05.
Results: Young people with CF presented with decreased lung function and maximal exercise capacity compared to matched controls. Baseline FMD was also significantly decreased in the CF group (CF: 5.23% v non-CF: 8.27% v non-CF active: 9.12%). Immediately post-training, FMD was significantly attenuated (approximately 40%) in all groups with CF still demonstrating the most minimal FMD. Follow-up measurements of FMD revealed a slow recovery towards baseline values 30 min post-training and improvements in the CF and non-CF active groups 60 min post-training. Linear regression exposed significant correlations between maximal exercise capacity (VO2 peak), BMI and FMD immediately post-training.
Conclusion: These new findings confirm that CF vascular endothelial dysfunction can be acutely modified by exercise and will aid in underlining the importance of exercise in CF populations. The potential benefits of long-term exercise interventions on vascular endothelial dysfunction in young people with CF warrants further investigation.
Die vorliegende Forschungsarbeit untersucht den Umgang mit Dilemmata von Topmanagern. Dilemmata sind ein alltägliches Geschäft im Topmanagement. Die entsprechenden Akteure sind daher immer wieder mit diesen konfrontiert und mit ihnen umzugehen, gehört gewissermaßen zu ihrer Berufsbeschreibung. Hinzu kommen Dilemmata im nicht direkt geschäftlichen Bereich, wie zum Beispiel jene zwischen Familien- und Arbeitszeit. Doch stellt dieses Feld ein kaum untersuchtes Forschungsgebiet dar. Während Dilemmata in anderen Bereichen eine zunehmende Aufmerksamkeit erfuhren, wurden deren Besonderheiten im Topmanagement genauso wenig differenziert betrachtet wie zugehörige Umgangsweisen. Theorie und Praxis stellen bezüglich Dilemmata von Topmanagern vor allem einen Gegensatz dar, beziehungsweise fehlt es an einer theoretischen Fundierung der Empirie. Diesem Umstand wird mittels dieser Studie begegnet. Auf der Grundlage einer differenzierten und breiten Erfassung von Theorien zu Dilemmata, so diese auch noch nicht auf Topmanager bezogen wurden, und einer empirischen Erhebung, die im Mittelpunkt dieser Arbeit stehen, soll das Feld Dilemmata von Topmanagern der Forschung geöffnet werden. Empirische Grundlage sind vor allem narrative Interviews mit Topmanagern über ihre Dilemmata-Wahrnehmung, ausgemachte Ursachen, Umgangsweisen und Resultate. Dies erlaubt es, Topmanagertypen sowie Dilemmata-Arten, mit denen sie konfrontiert sind oder waren, analytisch herauszuarbeiten. Angesichts der Praxisrelevanz von Dilemmata von Topmanagern wird jedoch nicht nur ein theoretisches Modell zu dieser Thematik erarbeitet, es werden auch Reflexionen auf die Praxis in Form von Handlungsempfehlungen vorgenommen. Schließlich gilt es, die allgemeine Theorie zu Dilemmata, ohne konkreten Bezug zu Topmanagern, mit den theoretischen Erkenntnissen dieser Studie auf empirischer Basis zu kontrastieren. Dabei wird im Rahmen der empirischen Erfassung und Auswertung dem Ansatz der Grounded-Theory-Methodologie gefolgt.
Im Rahmen dieser Dissertation konnten neue Kalium- und Natrium-Ionen Fluoreszenzfarbstoffe von der Klasse der Fluoroionophore synthetisiert und charakterisiert werden. Sie bestehen aus einem N Phenylazakronenether als Ionophor und unterschiedlichen Fluorophoren und sind über einen π-konjugierten 1,2,3-Triazol-1,4-diyl Spacer verbunden. Dabei lag der Fokus während ihrer Entwicklung darauf, diese in ihrer Sensitivität, Selektivität und in ihren photophysikalischen Eigenschaften so zu funktionalisieren, dass sie für intra- bzw. extrazelluläre Konzentrationsbestimmungen geeignet sind.
Durch Variation der in ortho Position der N-Phenylazakronenether befindlichen Alkoxy-Gruppen und der fluorophoren Gruppe der Fluoroionophore konnte festgestellt werden, dass die Sensitivität und Selektivität für Kalium- bzw. Natrium-Ionen jeweils durch eine bestimmte Isomerie der 1,2,3-Triazol-1,4-diyl-Einheit erhöht wird. Des Weiteren wurde gezeigt, dass durch eine erhöhte Einschränkung der N,N-Diethylamino-Gruppe des Fluorophors eine Steigerung der Fluoreszenzquantenausbeute und eine Verschiebung des Emissionsmaximums auf über 500 nm erreicht werden konnte. Die Einführung einer Isopropoxy-Gruppe an einem N-Phenylaza-[18]krone-6-ethers resultierte dabei in einem hoch selektiven Kalium-Ionen Fluoroionophor und ermöglichte eine in vitro Überwachung von 10 – 80 mM Kalium-Ionen. Die Substitution einer Methoxy-Gruppe an einem N-Phenylaza-[15]krone-5-ether kombiniert mit unterschiedlich N,N-Diethylamino-Coumarinen lieferte hingegen zwei Natrium-Ionen Fluoroionophore, die für die Überwachung von intra- bzw. extrazellulären Natrium-Ionen Konzentrationen geeignet sind.
In einem weiteren Schritt wurden N-Phenylaza-[18]krone-6-ether mit einem Fluorophor, basierend auf einem [1,3]-Dioxolo[4,5-f][1,3]benzodioxol-(DBD)-Grundgerüst, funktionalisiert. Die im Anschluss durchgeführten spektroskopischen Untersuchungen ergaben, dass die Isopropoxy-Gruppe in ortho Position des N-Phenylaza-[18]krone-6-ether in einen für extrazelluläre Kalium-Ionen Konzentrationen selektiven Fluoroionophor resultierte, der die Konzentrationsbestimmungen über die Fluoreszenzintensität und -lebensdauer ermöglicht.
In einem abschließenden Schritt konnte unter Verwendung eines Pyrens als fluorophore Gruppe ein weiterer für extrazelluläre Kalium-Ionen Konzentrationen geeigneter Fluoroionophor entwickelt werden. Die Bestimmung der Kalium-Ionen Konzentration erfolgte hierbei anhand der Fluoreszenzintensitätsverhältnisse bei zwei Emissionswellenlängen.
Insgesamt konnten 17 verschiedene neue Fluoroionophore für die Bestimmung von Kalium- bzw. Natrium-Ionen synthetisiert und charakterisiert werden. Sechs dieser neuen Moleküle ermöglichen in vitro Messungen der intra- oder extrazellulären Kalium- und Natrium-Ionen Konzentrationen und könnten zukünftig für in vivo Konzentrationsmessungen verwendet werden.
Cellulose derived polymers
(2019)
Plastics, such as polyethylene, polypropylene, and polyethylene terephthalate are part of our everyday lives in the form of packaging, household goods, electrical insulation, etc. These polymers are non-degradable and create many environmental problems and public health concerns. Additionally, these polymers are produced from finite fossils resources. With the continuous utilization of these limited resources, it is important to look towards renewable sources along with biodegradation of the produced polymers, ideally. Although many bio-based polymers are known, such as polylactic acid, polybutylene succinate adipate or polybutylene succinate, none have yet shown the promise of replacing conventional polymers like polyethylene, polypropylene and polyethylene terephthalate. Cellulose is one of the most abundant renewable resources produced in nature. It can be transformed into various small molecules, such as sugars, furans, and levoglucosenone. The aim of this research is to use the cellulose derived molecules for the synthesis of polymers.
Acid-treated cellulose was subjected to thermal pyrolysis to obtain levoglucosenone, which was reduced to levoglucosenol. Levoglucosenol was polymerized, for the first time, by ring-opening metathesis polymerization (ROMP) yielding high molar mass polymers of up to ~150 kg/mol. The poly(levoglucosenol) is thermally stable up to ~220 ℃, amorphous, and is exhibiting a relatively high glass transition temperature of ~100 ℃. The poly(levoglucosenol) can be converted to a transparent film, resembling common plastic, and was found to degrade in a moist acidic environment. This means that poly(levoglucosenol) may find its use as an alternative to conventional plastic, for instance, polystyrene.
Levoglucosenol was also converted into levoglucosenyl methyl ether, which was polymerized by cationic ring-opening metathesis polymerization (CROP). Polymers were obtained with molar masses up to ~36 kg/mol. These polymers are thermally stable up to ~220 ℃ and are semi-crystalline thermoplastics, having a glass transition temperature of ~35 ℃ and melting transition of 70-100 ℃. Additionally, the polymers underwent cross-linking, hydrogenation and thiol-ene click chemistry.
Risiken für Cyberressourcen können durch unbeabsichtigte oder absichtliche Bedrohungen entstehen. Dazu gehören Insider-Bedrohungen von unzufriedenen oder nachlässigen Mitarbeitern und Partnern, eskalierende und aufkommende Bedrohungen aus aller Welt, die stetige Weiterentwicklung der Angriffstechnologien und die Entstehung neuer und zerstörerischer Angriffe. Informationstechnik spielt mittlerweile in allen Bereichen des Lebens eine entscheidende Rolle, u. a. auch im Bereich des Militärs. Ein ineffektiver Schutz von Cyberressourcen kann hier Sicherheitsvorfälle und Cyberattacken erleichtern, welche die kritischen Vorgänge stören, zu unangemessenem Zugriff, Offenlegung, Änderung oder Zerstörung sensibler Informationen führen und somit die nationale Sicherheit, das wirtschaftliche Wohlergehen sowie die öffentliche Gesundheit und Sicherheit gefährden. Oftmals ist allerdings nicht klar, welche Bedrohungen konkret vorhanden sind und welche der kritischen Systemressourcen besonders gefährdet ist.
In dieser Dissertation werden verschiedene Analyseverfahren für Bedrohungen in militärischer Informationstechnik vorgeschlagen und in realen Umgebungen getestet. Dies bezieht sich auf Infrastrukturen, IT-Systeme, Netze und Anwendungen, welche Verschlusssachen (VS)/Staatsgeheimnisse verarbeiten, wie zum Beispiel bei militärischen oder Regierungsorganisationen. Die Besonderheit an diesen Organisationen ist das Konzept der Informationsräume, in denen verschiedene Datenelemente, wie z. B. Papierdokumente und Computerdateien, entsprechend ihrer Sicherheitsempfindlichkeit eingestuft werden, z. B. „STRENG GEHEIM“, „GEHEIM“, „VS-VERTRAULICH“, „VS-NUR-FÜR-DEN-DIENSTGEBRAUCH“ oder „OFFEN“.
Die Besonderheit dieser Arbeit ist der Zugang zu eingestuften Informationen aus verschiedenen Informationsräumen und der Prozess der Freigabe dieser. Jede in der Arbeit entstandene Veröffentlichung wurde mit Angehörigen in der Organisation besprochen, gegengelesen und freigegeben, so dass keine eingestuften Informationen an die Öffentlichkeit gelangen.
Die Dissertation beschreibt zunächst Bedrohungsklassifikationsschemen und Angreiferstrategien, um daraus ein ganzheitliches, strategiebasiertes Bedrohungsmodell für Organisationen abzuleiten. Im weiteren Verlauf wird die Erstellung und Analyse eines Sicherheitsdatenflussdiagramms definiert, welches genutzt wird, um in eingestuften Informationsräumen operationelle Netzknoten zu identifizieren, die aufgrund der Bedrohungen besonders gefährdet sind. Die spezielle, neuartige Darstellung ermöglicht es, erlaubte und verbotene Informationsflüsse innerhalb und zwischen diesen Informationsräumen zu verstehen.
Aufbauend auf der Bedrohungsanalyse werden im weiteren Verlauf die Nachrichtenflüsse der operationellen Netzknoten auf Verstöße gegen Sicherheitsrichtlinien analysiert und die Ergebnisse mit Hilfe des Sicherheitsdatenflussdiagramms anonymisiert dargestellt. Durch Anonymisierung der Sicherheitsdatenflussdiagramme ist ein Austausch mit externen Experten zur Diskussion von Sicherheitsproblematiken möglich.
Der dritte Teil der Arbeit zeigt, wie umfangreiche Protokolldaten der Nachrichtenflüsse dahingehend untersucht werden können, ob eine Reduzierung der Menge an Daten möglich ist. Dazu wird die Theorie der groben Mengen aus der Unsicherheitstheorie genutzt. Dieser Ansatz wird in einer Fallstudie, auch unter Berücksichtigung von möglichen auftretenden Anomalien getestet und ermittelt, welche Attribute in Protokolldaten am ehesten redundant sind.
Continuous insight into biological processes has led to the development of large-scale, mechanistic systems biology models of pharmacologically relevant networks. While these models are typically designed to study the impact of diverse stimuli or perturbations on multiple system variables, the focus in pharmacological research is often on a specific input, e.g., the dose of a drug, and a specific output related to the drug effect or response in terms of some surrogate marker.
To study a chosen input-output pair, the complexity of the interactions as well as the size of the models hinders easy access and understanding of the details of the input-output relationship.
The objective of this thesis is the development of a mathematical approach, in specific a model reduction technique, that allows (i) to quantify the importance of the different state variables for a given input-output relationship, and (ii) to reduce the dynamics to its essential features -- allowing for a physiological interpretation of state variables as well as parameter estimation in the statistical analysis of clinical data. We develop a model reduction technique using a control theoretic setting by first defining a novel type of time-limited controllability and observability gramians for nonlinear systems. We then show the superiority of the time-limited generalised gramians for nonlinear systems in the context of balanced truncation for a benchmark system from control theory.
The concept of time-limited controllability and observability gramians is subsequently used to introduce a state and time-dependent quantity called the input-response (ir) index that quantifies the importance of state variables for a given input-response relationship at a particular time.
We subsequently link our approach to sensitivity analysis, thus, enabling for the first time the use of sensitivity coefficients for state space reduction. The sensitivity based ir-indices are given as a product of two sensitivity coefficients. This allows not only for a computational more efficient calculation but also for a clear distinction of the extent to which the input impacts a state variable and the extent to which a state variable impacts the output.
The ir-indices give insight into the coordinated action of specific state variables for a chosen input-response relationship.
Our developed model reduction technique results in reduced models that still allow for a mechanistic interpretation in terms of the quantities/state variables of the original system, which is a key requirement in the field of systems pharmacology and systems biology and distinguished the reduced models from so-called empirical drug effect models. The ir-indices are explicitly defined with respect to a reference trajectory and thereby dependent on the initial state (this is an important feature of the measure). This is demonstrated for an example from the field of systems pharmacology, showing that the reduced models are very informative in their ability to detect (genetic) deficiencies in certain physiological entities. Comparing our novel model reduction technique to the already existing techniques shows its superiority.
The novel input-response index as a measure of the importance of state variables provides a powerful tool for understanding the complex dynamics of large-scale systems in the context of a specific drug-response relationship. Furthermore, the indices provide a means for a very efficient model order reduction and, thus, an important step towards translating insight from biological processes incorporated in detailed systems pharmacology models into the population analysis of clinical data.
This dissertation investigates the impact of the economic and fiscal crisis starting in 2008 on EU climate policy-making. While the overall number of adopted greenhouse gas emission reduction policies declined in the crisis aftermath, EU lawmakers decided to introduce new or tighten existing regulations in some important policy domains. Existing knowledge about the crisis impact on EU legislative decision-making cannot explain these inconsistencies. In response, this study develops an actor-centred conceptual framework based on rational choice institutionalism that provides a micro-level link to explain how economic crises translate into altered policy-making patterns. The core theoretical argument draws on redistributive conflicts, arguing that tensions between ‘beneficiaries’ and ‘losers’ of a regulatory initiative intensify during economic crises and spill over to the policy domain. To test this hypothesis and using social network analysis, this study analyses policy processes in three case studies: The introduction of carbon dioxide emission limits for passenger cars, the expansion of the EU Emissions Trading System to aviation, and the introduction of a regulatory framework for biofuels. The key finding is that an economic shock causes EU policy domains to polarise politically, resulting in intensified conflict and more difficult decision-making. The results also show that this process of political polarisation roots in the industry that is the subject of the regulation, and that intergovernmental bargaining among member states becomes more important, but also more difficult in times of crisis.
Fold and thrust belts are characteristic features of collisional orogen that grow laterally through time by deforming the upper crust in response to stresses caused by convergence. The deformation propagation in the upper crust is accommodated by shortening along major folds and thrusts. The formation of these structures is influenced by the mechanical strength of décollements, basement architecture, presence of preexisting structures and taper of the wedge. These factors control not only the sequence of deformation but also cause differences in the structural style.
The Himalayan fold and thrust belt exhibits significant differences in the structural style from east to west. The external zone of the Himalayan fold and thrust belt, also called the Subhimalaya, has been extensively studied to understand the temporal development and differences in the structural style in Bhutan, Nepal and India; however, the Subhimalaya in Pakistan remains poorly studied. The Kohat and Potwar fold and thrust belts (herein called Kohat and Potwar) represent the Subhimalaya in Pakistan. The Main Boundary Thrust (MBT) marks the northern boundary of both Kohat and Potwar, showing that these belts are genetically linked to foreland-vergent deformation within the Himalayan orogen, despite the pronounced contrast in structural style. This contrast becomes more pronounced toward south, where the active strike-slip Kalabagh Fault Zone links with the Kohat and Potwar range fronts, known as the Surghar Range and the Salt Range, respectively. The Surghar and Salt Ranges developed above the Surghar Thrust (SGT) and Main Frontal Thrust (MFT). In order to understand the structural style and spatiotemporal development of the major structures in Kohat and Potwar, I have used structural modeling and low temperature thermochronolgy methods in this study. The structural modeling is based on construction of balanced cross-sections by integrating surface geology, seismic reflection profiles and well data. In order to constrain the timing and magnitude of exhumation, I used apatite (U-Th-Sm)/He (AHe) and apatite fission track (AFT) dating. The results obtained from both methods are combined to document the Paleozoic to Recent history of Kohat and Potwar.
The results of this research suggest two major events in the deformation history. The first major deformation event is related to Late Paleozoic rifting associated with the development of the Neo-Tethys Ocean. The second major deformation event is related to the Late Miocene to Pliocene development of the Himalayan fold and thrust belt in the Kohat and Potwar. The Late Paleozoic rifting is deciphered by inverse thermal modelling of detrital AFT and AHe ages from the Salt Range. The process of rifting in this area created normal faulting that resulted in the exhumation/erosion of Early to Middle Paleozoic strata, forming a major unconformity between Cambrian and Permian strata that is exposed today in the Salt Range. The normal faults formed in Late Paleozoic time played an important role in localizing the Miocene-Pliocene deformation in this area. The combination of structural reconstructions and thermochronologic data suggest that deformation initiated at 15±2 Ma on the SGT ramp in the southern part of Kohat. The early movement on the SGT accreted the foreland into the Kohat deforming wedge, forming the range front. The development of the MBT at 12±2 Ma formed the northern boundary of Kohat and Potwar. Deformation propagated south of the MBT in the Kohat on double décollements and in the Potwar on a single basal décollement. The double décollement in the Kohat adopted an active roof-thrust deformation style that resulted in the disharmonic structural style in the upper and lower parts of the stratigraphic section. Incremental shortening resulted in the development of duplexes in the subsurface between two décollements and imbrication above the roof thrust. Tectonic thickening caused by duplexes resulted in cooling and exhumation above the roof thrust by removal of a thick sequence of molasse strata. The structural modelling shows that the ramps on which duplexes formed in Kohat continue as tip lines of fault propagation folds in the Potwar. The absence of a double décollement in the Potwar resulted in the preservation of a thick sequence of molasse strata there. The temporal data suggest that deformation propagated in-sequence from ~ 8 to 3 Ma in the northern part of Kohat and Potwar; however, internal deformation in the Kohat was more intense, probably required for maintaining a critical taper after a significant load was removed above the upper décollement. In the southern part of Potwar, a steeper basement slope (β≥3°) and the presence of salt at the base of the stratigraphic section allowed for the complete preservation of the stratigraphic wedge, showcased by very little internal deformation. Activation of the MFT at ~4 Ma allowed the Salt Range to become the range front of the Potwar. The removal of a large amount of molasse strata above the MFT ramp enhanced the role of salt in shaping the structural style of the Salt Range and Kalabagh Fault Zone. Salt accumulation and migration resulted in the formation of normal faults in both areas. Salt migration in the Kalabagh fault zone has triggered out-of-sequence movement on ramps in the Kohat.
The amount of shortening calculated between the MBT and the SGT in Kohat is 75±5 km and between the MBT and the MFT in Potwar is 65±5 km. A comparable amount of shortening is accommodated in the Kohat and Potwar despite their different widths: 70 km Kohat and 150 km Potwar. In summary, this research suggests that deformation switched between different structures during the last ~15 Ma through different modes of fault propagation, resulting in different structural styles and the out-of-sequence development of Kohat and Potwar.
The foreland of the Andes in South America is characterised by distinct along strike changes in surface deformational styles. These styles are classified into two end-members, the thin-skinned and the thick-skinned style. The superficial expression of thin-skinned deformation is a succession of narrowly spaced hills and valleys, that form laterally continuous ranges on the foreland facing side of the orogen. Each of the hills is defined by a reverse fault that roots in a basal décollement surface within the sedimentary cover, and acted as thrusting ramp to stack the sedimentary pile. Thick-skinned deformation is morphologically characterised by spatially disparate, basement-cored mountain ranges. These mountain ranges are uplifted along reactivated high-angle crustal-scale discontinuities, such as suture zones between different tectonic terranes.
Amongst proposed causes for the observed variation are variations in the dip angle of the Nazca plate, variation in sediment thickness, lithospheric thickening, volcanism or compositional differences. The proposed mechanisms are predominantly based on geological observations or numerical thermomechanical modelling, but there has been no attempt to understand the mechanisms from a point of data-integrative 3D modelling. The aim of this dissertation is therefore to understand how lithospheric structure controls the deformational behaviour. The integration of independent data into a consistent model of the lithosphere allows to obtain additional evidence that helps to understand the causes for the different deformational styles. Northern Argentina encompasses the transition from the thin-skinned fold-and-thrust belt in Bolivia, to the thick-skinned Sierras Pampeanas province, which makes this area a well suited location for such a study. The general workflow followed in this study first involves data-constrained structural- and density-modelling in order to obtain a model of the study area. This model was then used to predict the steady-state thermal field, which was then used to assess the present-day rheological state in northern Argentina.
The structural configuration of the lithosphere in northern Argentina was determined by means of data-integrative, 3D density modelling verified by Bouguer gravity. The model delineates the first-order density contrasts in the lithosphere in the uppermost 200 km, and discriminates bodies for the sediments, the crystalline crust, the lithospheric mantle and the subducting Nazca plate. To obtain the intra-crustal density structure, an automated inversion approach was developed and applied to a starting structural model that assumed a homogeneously dense crust. The resulting final structural model indicates that the crustal structure can be represented by an upper crust with a density of 2800 kg/m³, and a lower crust of 3100 kg/m³. The Transbrazilian Lineament, which separates the Pampia terrane from the Río de la Plata craton, is expressed as a zone of low average crustal densities.
In an excursion, we demonstrate in another study, that the gravity inversion method developed to obtain intra-crustal density structures, is also applicable to obtain density variations in the uppermost lithospheric mantle. Densities in such sub-crustal depths are difficult to constrain from seismic tomographic models due to smearing of crustal velocities. With the application to the uppermost lithospheric mantle in the north Atlantic, we demonstrate in Tan et al. (2018) that lateral density trends of at least 125\,km width are robustly recovered by the inversion method, thereby providing an important tool for the delineation of subcrustal density trends.
Due to the genetic link between subduction, orogenesis and retroarc foreland basins the question rises whether the steady-state assumption is valid in such a dynamic setting. To answer this question, I analysed (i) the impact of subduction on the conductive thermal field of the overlying continental plate, (ii) the differences between the transient and steady-state thermal fields of a geodynamic coupled model. Both studies indicate that the assumption of a thermal steady-state is applicable in most parts of the study area. Within the orogenic wedge, where the assumption cannot be applied, I estimated the transient thermal field based on the results of the conducted analyses.
Accordingly, the structural model that had been obtained in the first step, could be used to obtain a 3D conductive steady-state thermal field. The rheological assessment based on this thermal field indicates that the lithosphere of the thin-skinned Subandean ranges is characterised by a relatively strong crust and a weak mantle. Contrarily, the adjacent foreland basin consists of a fully coupled, very strong lithosphere. Thus, shortening in northern Argentina can only be accommodated within the weak lithosphere of the orogen and the Subandean ranges. The analysis suggests that the décollements of the fold-and-thrust belt are the shallow continuation of shear zones that reside in the ductile sections of the orogenic crust. Furthermore, the localisation of the faults that provide strain transfer between the deeper ductile crust and the shallower décollement is strongly influenced by crustal weak zones such as foliation. In contrast to the northern foreland, the lithosphere of the thick-skinned Sierras Pampeanas is fully coupled and characterised by a strong crust and mantle. The high overall strength prevents the generation of crustal-scale faults by tectonic stresses. Even inherited crustal-scale discontinuities, such as sutures, cannot sufficiently reduce the strength of the lithosphere in order to be reactivated. Therefore, magmatism that had been identified to be a precursor of basement uplift in the Sierras Pampeanas, is the key factor that leads to the broken foreland of this province. Due to thermal weakening, and potentially lubrication of the inherited discontinuities, the lithosphere is locally weakened such that tectonic stresses can uplift the basement blocks. This hypothesis explains both the spatially disparate character of the broken foreland, as well as the observed temporal delay between volcanism and basement block uplift.
This dissertation provides for the first time a data-driven 3D model that is consistent with geophysical data and geological observations, and that is able to causally link the thermo-rheological structure of the lithosphere to the observed variation of surface deformation styles in the retroarc foreland of northern Argentina.
The fabrication of 1D nanostrands composed of stimuli responsive microgels has been shown in this work. Microgels are well known materials able to respond to various stimuli from outer environment. Since these microgels respond via a volume change to an external stimulus, a targeted mechanical response can be achieved. Through carefully choosing the right composition of the polymer matrix, microgels can be designed to react precisely to the targeted stimuli (e.g. drug delivery via pH and temperature changes, or selective contractions through changes in electrical current125).
In this work, it was aimed to create flexible nano-filaments which are capable of fast anisotropic contractions similar to muscle filaments. For the fabrication of such filaments or strands, nanostructured templates (PDMS wrinkles) were chosen due to a facile and low-cost fabrication and versatile tunability of their dimensions. Additionally, wrinkling is a well-known lithography-free method which enables the fabrication of nanostructures in a reproducible manner and with a high long-range periodicity.
In Chapter 2.1, it was shown for the first time that microgels as soft matter particles can be aligned to densely packed microgel arrays of various lateral dimensions. The alignment of microgels with different compositions (e.g. VCL/AAEM, NIPAAm, NIPAAm/VCL and charged microgels) was shown by using different assembly techniques (e.g. spin-coating, template confined molding). It was chosen to set one experimental parameter constant which was the SiOx surface composition of the templates and substrates (e.g. oxidized PDMS wrinkles, Si-wafers and glass slides). It was shown that the fabrication of nanoarrays was feasible with all tested microgel types. Although the microgels exhibited different deformability when aligned on a flat surface, they retained their thermo-responsivity and swelling behavior.
Towards the fabrication of 1D microgel strands interparticle connectivity was aspired. This was achieved via different cross-linking methods (i.e. cross-linking via UV-irradiation and host-guest complexation) discussed in Chapter 2.2. The microgel arrays created by different assembly methods and microgel types were tested for their cross-linking suitability. It was observed that NIPAAm based microgels cannot be cross-linked with UV light. Furthermore, it was found that these microgels exhibit a strong surface-particle-interaction and therefore could not be detached from the given substrates. In contrast to the latter, with VCL/AAEM based microgels it was possible to both UV cross-link them based on the keto-enol tautomerism of the AAEM copolymer, and to detach them from the substrate due to the lower adhesion energy towards SiOx surfaces. With VCL/AAEM microgels long, one-dimensional microgel strands could be re-dispersed in water for further analysis. It has also been shown that at least one lateral dimension of the free dispersed 1D microgel strands is easily controllable by adjusting the wavelength of the wrinkled template. For further work, only VCL/AAEM based microgels were used to focus on the main aim of this work, i.e. the fabrication of 1D microgel nanostrands.
As an alternative to the unspecific and harsh UV cross-linking, the host-guest complexation via diazobenzene cross-linkers and cyclodextrin hosts was explored. The idea behind this approach was to give means to a future construction kit-like approach by incorporation of cyclodextrin comonomers in a broad variety of particle systems (e.g. microgels, nanoparticles). For this purpose, VCL/AAEM microgels were copolymerized with different amounts of mono-acrylate functionalized β-cyclodextrin (CD). After successfully testing the cross-linking capability in solution, the cross-linking of aligned VCL/AAEM/CD microgels was tried. Although the cross-linking worked well, once the single arrays came into contact to each other, they agglomerated. As a reason for this behavior residual amounts of mono-complexed diazobenzene linkers were suspected. Thus, end-capping strategies were tried out (e.g. excess amounts of β-cyclodextrin and coverage with azobenzene functionalized AuNPs) but were unsuccessful. With deeper thought, entropy effects were taken into consideration which favor the release of complexed diazobenzene linker leading to agglomerations. To circumvent this entropy driven effect, a multifunctional polymer with 50% azobenzene groups (Harada polymer) was used. First experiments with this polymer showed promising results regarding a less pronounced agglomeration (Figure 77). Thus, this approach could be pursued in the future. In this chapter it was found out that in contrast to pearl necklace and ribbon like formations, particle alignment in zigzag formation provided the best compromise in terms of stability in dispersion (see Figure 44a and Figure 51) while maintaining sufficient flexibility.
For this reason, microgel strands in zigzag formation were used for the motion analysis described in Chapter 2.3. The aim was to observe the properties of unrestrained microgel strands in solution (e.g. diffusion behavior, rotational properties and ideally, anisotropic contraction after temperature increase). Initially, 1D microgel strands were manipulated via AFM in a liquid cell setup. It could be observed that the strands required a higher load force compared to single microgels to be detached from the surface. However, with the AFM it was not possible to detach the strands in a controllable manner but resulted in a complete removal of single microgel particles and a tearing off the strands from the surface, respectively. For this reason, to observe the motion behavior of unrestrained microgel strands in solution, confocal microscopy was used. Furthermore, to hinder an adsorption of the strands, it was found out that coating the surface of the substrates with a repulsive polymer film was beneficial. Confocal and wide-field microscopy videos showed that the microgel strands exhibit translational and rotational diffusive motion in solution without perceptible bending. Unfortunately, with these methods the detection of the anisotropic stimuli responsive contraction of the free moving microgel strands was not possible. To summarize, the flexibility of microgel strands is more comparable to the mechanical behavior of a semi flexible cable than to a yarn. The strands studied here consist of dozens or even hundreds of discrete submicron units strung together by cross-linking, having few parallels in nanotechnology.
With the insights gained in this work on microgel-surface interactions, in the future, a targeted functionalization of the template and substrate surfaces can be conducted to actively prevent unwanted microgel adsorption for a given microgel system (e.g. PVCL and polystyrene coating235). This measure would make the discussed alignment methods more diverse. As shown herein, the assembly methods enable a versatile microgel alignment (e.g. microgel meshes, double and triple strands). To go further, one could use more complex templates (e.g. ceramic rhombs and star shaped wrinkles (Figure 14) to expand the possibilities of microgel alignment and to precisely control their aspect ratios (e.g. microgel rods with homogeneous size distributions).
Over the last years there is an increasing awareness that historical land cover changes and associated land use legacies may be important drivers for present-day species richness and biodiversity due to time-delayed extinctions or colonizations in response to historical environmental changes. Historically altered habitat patches may therefore exhibit an extinction debt or colonization credit and can be expected to lose or gain species in the future. However, extinction debts and colonization credits are difficult to detect and their actual magnitudes or payments have rarely been quantified because species richness patterns and dynamics are also shaped by recent environmental conditions and recent environmental changes.
In this thesis we aimed to determine patterns of herb-layer species richness and recent species richness dynamics of forest herb layer plants and link those patterns and dynamics to historical land cover changes and associated land use legacies. The study was conducted in the Prignitz, NE-Germany, where the forest distribution remained stable for the last ca. 100 years but where a) the deciduous forest area had declined by more than 90 per cent (leaving only remnants of "ancient forests"), b) small new forests had been established on former agricultural land ("post-agricultural forests"). Here, we analyzed the relative importance of land use history and associated historical land cover changes for herb layer species richness compared to recent environmental factors and determined magnitudes of extinction debt and colonization credit and their payment in ancient and post-agricultural forests, respectively.
We showed that present-day species richness patterns were still shaped by historical land cover changes that ranged back to more than a century. Although recent environmental conditions were largely comparable we found significantly more forest specialists, species with short-distance dispersal capabilities and clonals in ancient forests than in post-agricultural forests. Those species richness differences were largely contingent to a colonization credit in post-agricultural forests that ranged up to 9 species (average 4.7), while the extinction debt in ancient forests had almost completely been paid. Environmental legacies from historical agricultural land use played a minor role for species richness differences. Instead, patch connectivity was most important. Species richness in ancient forests was still dependent on historical connectivity, indicating a last glimpse of an extinction debt, and the colonization credit was highest in isolated post-agricultural forests. In post-agricultural forests that were better connected or directly adjacent to ancient forest patches the colonization credit was way smaller and we were able to verify a gradual payment of the colonization credit from 2.7 species to 1.5 species over the last six decades.
With the growth of information technology, patient attitudes are shifting – away from passively receiving care towards actively taking responsibility for their well- being. Handling doctor-patient relationships collaboratively and providing patients access to their health information are crucial steps in empowering patients. In mental healthcare, the implicit consensus amongst practitioners has been that sharing medical records with patients may have an unpredictable, harmful impact on clinical practice. In order to involve patients more actively in mental healthcare processes, Tele-Board MED (TBM) allows for digital collaborative documentation in therapist-patient sessions. The TBM software system offers a whiteboard-inspired graphical user interface that allows therapist and patient to jointly take notes during the treatment session. Furthermore, it provides features to automatically reuse the digital treatment session notes for the creation of treatment session summaries and clinical case reports. This thesis presents the development of the TBM system and evaluates its effects on 1) the fulfillment of the therapist’s duties of clinical case documentation, 2) patient engagement in care processes, and 3) the therapist-patient relationship. Following the design research methodology, TBM was developed and tested in multiple evaluation studies in the domains of cognitive behavioral psychotherapy and addiction care. The results show that therapists are likely to use TBM with patients if they have a technology-friendly attitude and when its use suits the treatment context. Support in carrying out documentation duties as well as fulfilling legal requirements contributes to therapist acceptance. Furthermore, therapists value TBM as a tool to provide a discussion framework and quick access to worksheets during treatment sessions. Therapists express skepticism, however, regarding technology use in patient sessions and towards complete record transparency in general. Patients expect TBM to improve the communication with their therapist and to offer a better recall of discussed topics when taking a copy of their notes home after the session. Patients are doubtful regarding a possible distraction of the therapist and usage in situations when relationship-building is crucial. When applied in a clinical environment, collaborative note-taking with TBM encourages patient engagement and a team feeling between therapist and patient. Furthermore, it increases the patient’s acceptance of their diagnosis, which in turn is an important predictor for therapy success. In summary, TBM has a high potential to deliver more than documentation support and record transparency for patients, but also to contribute to a collaborative doctor-patient relationship. This thesis provides design implications for the development of digital collaborative documentation systems in (mental) healthcare as well as recommendations for a successful implementation in clinical practice.
Restful choreographies
(2019)
Business process management has become a key instrument to organize work as many companies represent their operations in business process models. Recently, business process choreography diagrams have been introduced as part of the Business Process Model and Notation standard to represent interactions between business processes, run by different partners. When it comes to the interactions between services on the Web, Representational State Transfer (REST) is one of the primary architectural styles employed by web services today. Ideally, the RESTful interactions between participants should implement the interactions defined at the business choreography level.
The problem, however, is the conceptual gap between the business process choreography diagrams and RESTful interactions. Choreography diagrams, on the one hand, are modeled from business domain experts with the purpose of capturing, communicating and, ideally, driving the business interactions. RESTful interactions, on the other hand, depend on RESTful interfaces that are designed by web engineers with the purpose of facilitating the interaction between participants on the internet. In most cases however, business domain experts are unaware of the technology behind web service interfaces and web engineers tend to overlook the overall business goals of web services. While there is considerable work on using process models during process implementation, there is little work on using choreography models to implement interactions between business processes. This thesis addresses this research gap by raising the following research question: How to close the conceptual gap between business process choreographies and RESTful interactions? This thesis offers several research contributions that jointly answer the research question.
The main research contribution is the design of a language that captures RESTful interactions between participants---RESTful choreography modeling language. Formal completeness properties (with respect to REST) are introduced to validate its instances, called RESTful choreographies. A systematic semi-automatic method for deriving RESTful choreographies from business process choreographies is proposed. The method employs natural language processing techniques to translate business interactions into RESTful interactions. The effectiveness of the approach is shown by developing a prototypical tool that evaluates the derivation method over a large number of choreography models.
In addition, the thesis proposes solutions towards implementing RESTful choreographies. In particular, two RESTful service specifications are introduced for aiding, respectively, the execution of choreographies' exclusive gateways and the guidance of RESTful interactions.
Quantum field theory on curved spacetimes is understood as a semiclassical approximation of some quantum theory of gravitation, which models a quantum field under the influence of a classical gravitational field, that is, a curved spacetime. The most remarkable effect predicted by this approach is the creation of particles by the spacetime itself, represented, for instance, by Hawking's evaporation of black holes or the Unruh effect. On the other hand, these aspects already suggest that certain cornerstones of Minkowski quantum field theory, more precisely a preferred vacuum state and, consequently, the concept of particles, do not have sensible counterparts within a theory on general curved spacetimes. Likewise, the implementation of covariance in the model has to be reconsidered, as curved spacetimes usually lack any non-trivial global symmetry. Whereas this latter issue has been resolved by introducing the paradigm of locally covariant quantum field theory (LCQFT), the absence of a reasonable concept for distinct vacuum and particle states on general curved spacetimes has become manifest even in the form of no-go-theorems.
Within the framework of algebraic quantum field theory, one first introduces observables, while states enter the game only afterwards by assigning expectation values to them. Even though the construction of observables is based on physically motivated concepts, there is still a vast number of possible states, and many of them are not reasonable from a physical point of view. We infer that this notion is still too general, that is, further physical constraints are required. For instance, when dealing with a free quantum field theory driven by a linear field equation, it is natural to focus on so-called quasifree states. Furthermore, a suitable renormalization procedure for products of field operators is vitally important. This particularly concerns the expectation values of the energy momentum tensor, which correspond to distributional bisolutions of the field equation on the curved spacetime. J. Hadamard's theory of hyperbolic equations provides a certain class of bisolutions with fixed singular part, which therefore allow for an appropriate renormalization scheme.
By now, this specification of the singularity structure is known as the Hadamard condition and widely accepted as the natural generalization of the spectral condition of flat quantum field theory. Moreover, due to Radzikowski's celebrated results, it is equivalent to a local condition, namely on the wave front set of the bisolution. This formulation made the powerful tools of microlocal analysis, developed by Duistermaat and Hörmander, available for the verification of the Hadamard property as well as the construction of corresponding Hadamard states, which initiated much progress in this field. However, although indispensable for the investigation in the characteristics of operators and their parametrices, microlocal analyis is not practicable for the study of their non-singular features and central results are typically stated only up to smooth objects. Consequently, Radzikowski's work almost directly led to existence results and, moreover, a concrete pattern for the construction of Hadamard bidistributions via a Hadamard series. Nevertheless, the remaining properties (bisolution, causality, positivity) are ensured only modulo smooth functions.
It is the subject of this thesis to complete this construction for linear and formally self-adjoint wave operators acting on sections in a vector bundle over a globally hyperbolic Lorentzian manifold. Based on Wightman's solution of d'Alembert's equation on Minkowski space and the construction for the advanced and retarded fundamental solution, we set up a Hadamard series for local parametrices and derive global bisolutions from them. These are of Hadamard form and we show existence of smooth bisections such that the sum also satisfies the remaining properties exactly.
This is a publication-based dissertation comprising three original research stud-ies (one published, one submitted and one ready for submission; status March 2019). The dissertation introduces a generic computer model as a tool to investigate the behaviour and population dynamics of animals in cyclic environments. The model is further employed for analysing how migratory birds respond to various scenarios of altered food supply under global change. Here, ecological and evolutionary time-scales are considered, as well as the biological constraints and trade-offs the individual faces, which ultimately shape response dynamics at the population level. Further, the effect of fine-scale temporal patterns in re-source supply are studied, which is challenging to achieve experimentally. My findings predict population declines, altered behavioural timing and negative carry-over effects arising in migratory birds under global change. They thus stress the need for intensified research on how ecological mechanisms are affected by global change and for effective conservation measures for migratory birds. The open-source modelling software created for this dissertation can now be used for other taxa and related research questions. Overall, this thesis improves our mechanistic understanding of the impacts of global change on migratory birds as one prerequisite to comprehend ongoing global biodiversity loss. The research results are discussed in a broader ecological and scientific context in a concluding synthesis chapter.
With the emergence of the Internet of things (IoT), plenty of battery-powered and energy-harvesting devices are being deployed to fulfill sensing and actuation tasks in a variety of application areas, such as smart homes, precision agriculture, smart cities, and industrial automation. In this context, a critical issue is that of denial-of-sleep attacks. Such attacks temporarily or permanently deprive battery-powered, energy-harvesting, or otherwise energy-constrained devices of entering energy-saving sleep modes, thereby draining their charge. At the very least, a successful denial-of-sleep attack causes a long outage of the victim device. Moreover, to put battery-powered devices back into operation, their batteries have to be replaced. This is tedious and may even be infeasible, e.g., if a battery-powered device is deployed at an inaccessible location. While the research community came up with numerous defenses against denial-of-sleep attacks, most present-day IoT protocols include no denial-of-sleep defenses at all, presumably due to a lack of awareness and unsolved integration problems. After all, despite there are many denial-of-sleep defenses, effective defenses against certain kinds of denial-of-sleep attacks are yet to be found.
The overall contribution of this dissertation is to propose a denial-of-sleep-resilient medium access control (MAC) layer for IoT devices that communicate over IEEE 802.15.4 links. Internally, our MAC layer comprises two main components. The first main component is a denial-of-sleep-resilient protocol for establishing session keys among neighboring IEEE 802.15.4 nodes. The established session keys serve the dual purpose of implementing (i) basic wireless security and (ii) complementary denial-of-sleep defenses that belong to the second main component. The second main component is a denial-of-sleep-resilient MAC protocol. Notably, this MAC protocol not only incorporates novel denial-of-sleep defenses, but also state-of-the-art mechanisms for achieving low energy consumption, high throughput, and high delivery ratios. Altogether, our MAC layer resists, or at least greatly mitigates, all denial-of-sleep attacks against it we are aware of. Furthermore, our MAC layer is self-contained and thus can act as a drop-in replacement for IEEE 802.15.4-compliant MAC layers. In fact, we implemented our MAC layer in the Contiki-NG operating system, where it seamlessly integrates into an existing protocol stack.
Interactions and feedbacks between tectonics, climate, and upper plate architecture control basin geometry, relief, and depositional systems. The Andes is part of a longlived continental margin characterized by multiple tectonic cycles which have strongly modified the Andean upper plate architecture. In the Andean retroarc, spatiotemporal variations in the structure of the upper plate and tectonic regimes have resulted in marked along-strike variations in basin geometry, stratigraphy, deformational style, and mountain belt morphology. These along-strike variations include high-elevation plateaus (Altiplano and Puna) associated with a thin-skin fold-and-thrust-belt and thick-skin deformation in broken foreland basins such as the Santa Barbara system and the Sierras Pampeanas. At the confluence of the Puna Plateau, the Santa Barbara system and the Sierras Pampeanas, major along-strike changes in upper plate architecture, mountain belt morphology, basement exhumation, and deformation style can be recognized. I have used a source to sink approach to unravel the spatiotemporal tectonic evolution of the Andean retroarc between 26 and 28°S. I obtained a large low-temperature thermochronology data set from basement units which includes apatite fission track, apatite U-Th-Sm/He, and zircon U-Th/He (ZHe) cooling ages. Stratigraphic descriptions of Miocene units were temporally constrained by U-Pb LA-ICP-MS zircon ages from interbedded pyroclastic material.
Modeled ZHe ages suggest that the basement of the study area was exhumed during the Famatinian orogeny (550-450 Ma), followed by a period of relative tectonic quiescence during the Paleozoic and the Triassic. The basement experienced horst exhumation during the Cretaceous development of the Salta rift. After initial exhumation, deposition of thick Cretaceous syn-rift strata caused reheating of several basement blocks within the Santa Barbara system. During the Eocene-Oligocene, the Andean compressional setting was responsible for the exhumation of several disconnected basement blocks. These exhumed blocks were separated by areas of low relief, in which humid climate and low erosion rates facilitated the development of etchplains on the crystalline basement. The exhumed basement blocks formed an Eocene to Oligocene broken foreland basin in the back-bulge depozone of the Andean foreland. During the Early Miocene, foreland basin strata filled up the preexisting Paleogene topography. The basement blocks in lower relief positions were reheated; associated geothermal gradients were higher than 25°C/km. Miocene volcanism was responsible for lateral variations on the amount of reheating along the Campo-Arenal basin. Around 12 Ma, a new deformational phase modified the drainage network and fragmented the lacustrine system. As deformation and rock uplift continued, the easily eroded sedimentary cover was efficiently removed and reworked by an ephemeral fluvial system, preventing the development of significant relief. After ~6 Ma, the low erodibility of the basement blocks which began to be exposed caused relief increase, leading to the development of stable fluvial systems. Progressive relief development modified atmospheric circulation, creating a rainfall gradient. After 3 Ma, orographic rainfall and high relief lead to the development of proximal fluvial-gravitational depositional systems in the surrounding basins.