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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.
Bildungsort Familie
(2019)
In der Bildungs- und Familienforschung wird die intergenerationale Weitergabe von Bildung innerhalb der Familie hauptsächlich unter dem Blickwinkel des schulischen Erfolges der nachwachsenden Generation thematisiert. „Wie“ aber bildungsbezogene Transferprozesse innerhalb der Familie konkret ablaufen, bleibt jedoch in der deutschen Forschungslandschaft weitestgehend unbearbeitet. An dieser Stelle setzt diese qualitativ angelegte Arbeit an. Ziel dieser Arbeit ist, bildungsbezogene Transferprozesse innerhalb von russischen Dreigenerationenfamilien, die aus der ehemaligen Sowjetunion nach Berlin seit 1989 ausgewandert sind und zwischen der Großeltern-, Elterngeneration und der Enkelgeneration ablaufen, zu untersuchen. Hinter diesen Transferprozessen verbergen sich im Sinne Bourdieus bewusste und unbewusste Bildungsstrategien der interviewten Familienmitglieder. Im Rahmen dieser Arbeit wurden zwei Spätaussiedlerfamilien – zu diesen zählen Familie Hoffmann und Familie Popow, sowie zwei russisch-jüdische Familien – zu diesen zählen Familie Rosenthal und Familie Buchbinder, interviewt. Es wurden mit den einzelnen Mitgliedern der vier untersuchten Dreigenerationenfamilien Gruppendiskussionen sowie mit je einem Vertreter einer Generation leitfadengestützte Einzelinterviews geführt. Die Erhebungsphase fand in Berlin im Zeitraum von 2010 bis 2012 statt. Das auf diese Weise gewonnene empirische Material wurde mithilfe der dokumentarischen Methode nach Bohnsack ausgewertet. Hierdurch wurde es möglich die implizite Selbstverständlichkeit, mit der sich Bildung in Familien nach Bourdieu habituell vollzieht, einzufangen und rekonstruierbar zu machen. In der Arbeit wurden eine habitustheoretische Interpretation der russischen Dreigenerationenfamilien und die entsprechende Feldanalyse nach Bourdieu vorgenommen. In diesem Zusammenhang wurde der soziale Raum der untersuchten Familien in der Ankunftsgesellschaft bezüglich ihres Vergleichshorizontes der Herkunftsgesellschaft rekonstruiert. Weiter wurde der Bildungstransfer vor dem jeweiligen Erlebnishintergrund der einzelnen Familien untersucht und diesbezüglich eine Typisierung vorgenommen.
Im Rahmen dieser Untersuchung konnten neue Erkenntnisse zum bisher unerforschten Feld des Bildungstransfers russischer Dreigenerationenfamilien in Berlin gewonnen werden. Ein wesentliches Ergebnis dieser Arbeit ist, dass die Anwendung von Bourdieus Klassentheorie auch auf Gruppen, die in einer sozialistischen Gesellschaft sozialisiert wurden und in eine kapitalistisch orientierte Gesellschaft ausgewandert sind, produktiv sein kann. Ein weiteres zentrales Ergebnis der Studie ist, dass bei zwei der vier untersuchten Familien die Migration den intergenerationalen Bildungstransfer beeinflusste. In diesem Zusammenhang weist Familie Rosenthal durch die Migration einen „gespaltenen“ Habitus auf. Dieser ist darauf zurückzuführen, dass diese Familie bei der Planung des Berufes für die Enkelin in Berlin sich am Praktischen und Notwendigen orientierte. Während die bewusste Bildungsstrategie der Großeltern- und Elterngeneration für die Enkelgeneration im Ankunftsland dem Habitus der Notwendigkeit, den Bourdieu der Arbeiterklasse zuschreibt, zugeordnet werden kann, lässt sich hingegen das Freizeitverhalten der Familie Rosenthal dem Habitus der Distinktion zuordnen, der typisch für die herrschende Klasse ist. Ein weiterer Befund dieser Untersuchung ist, dass im Vergleich zur Enkelin Rosenthal bei der Enkelin Popow eine sogenannte Sphärendiskrepanz rekonstruiert wurde. So ist die Enkelin Popow in der äußeren Sphäre der Schule auf sich gestellt, da die Großeltern- und Elterngeneration zum deutschen Schulsystem nur über einen geringen Informationsstand verfügen. Die Enkelin grenzt sich einerseits von ihrer Familie (innere Sphäre) und deutschen Schulabbrechern (äußere Sphäre) ab, orientiert sich aber andererseits beim Versuch sozial aufzusteigen an russischsprachigen Peers, die die gymnasiale Oberstufe besuchen (dritte Sphäre). Bei Enkelin Popow fungiert demzufolge die Peergruppe und nicht die Familie als zentraler Bildungsort. An dieser Stelle sei angemerkt, dass sowohl bei einer russisch-jüdischen Familie als auch bei einer Spätaussiedlerfamilie der intergenerationale Bildungstransfer durch die Migration beeinflusst wurde. Während Familie Rosenthal in der Herkunftsgesellschaft der Intelligenzija zuzuordnen ist, gehört Familie Popow der Arbeiterschaft an. Daraus folgt, dass der intergenerationale Bildungstransfer der untersuchten Familien sowohl unabhängig vom Spätaussiedler- und Kontingentflüchtlingsstatus als auch vom herkunftsortspezifischen sozialen Status abläuft. Demnach kann geschlussfolgert werden, dass im Rahmen dieser Studie die Migration ein zentraler Faktor für den intergenerationalen Bildungstransfer ist.
C-Arylglykoside und Chalkone
(2019)
Im bis heute andauernden Zeitalter der wissenschaftlichen Medizin, konnte ein breites Spektrum von Wirkstoffen zur Behandlung diverser Krankheiten zusammengetragen werden. Dennoch hat es sich die organische Synthesechemie zur Aufgabe gemacht, dieses Spektrum auf neuen oder bekannten Wegen und aus verschiedenen Gründen zu erweitern. Zum einen ist das Vorkommen bestimmter Verbindungen in der Natur häufig limitiert, sodass synthetische Methoden immer öfter an Stelle eines weniger nachhaltigen Abbaus treten. Zum anderen kann durch Derivatisierung und Wirkstoffanpassung die physiologische Wirkung oder die Bioverfügbarkeit eines Wirkstoffes erhöht werden. In dieser Arbeit konnten einige Vertreter der bekannten Wirkstoffklassen C-Arylglykoside und Chalkone durch den Schlüsselschritt der Palladium-katalysierten MATSUDA-HECK-Reaktion synthetisiert werden.
Dazu wurden im Fall der C-Arylglykoside zunächst ungesättigte Kohlenhydrate (Glykale) über eine Ruthenium-katalysierte Zyklisierungsreaktion dargestellt. Diese wurden im Anschluss mit unterschiedlich substituierten Diazoniumsalzen in der oben erwähnten Palladium-katalysierten Kupplungsreaktion zur Reaktion gebracht. Bei der Auswertung der analytischen Daten konnte festgestellt werden, dass stets die trans-Diastereomere gebildet wurden. Im Anschluss konnte gezeigt werden, dass die Doppelbindungen dieser Verbindungen durch Hydrierung, Dihydroxylierung oder Epoxidierung funktionalisiert werden können. Auf diesem Wege konnte u. a. eine dem Diabetesmedikament Dapagliflozin ähnliche Verbindung hergestellt werden.
Im zweiten Teil der Arbeit wurden Arylallylchromanone durch die MATSUDA-HECK-Reaktion von verschiedenen 8-Allylchromanonen mit Diazoniumsalzen dargestellt. Dabei konnte beobachtet werden, dass eine MOM-Schutzgruppe in 7-Position der Moleküle die Darstellung von Produktgemischen unterdrückt und jeweils nur eine der möglichen Verbindungen gebildet wird. Die Lage der Doppelbindung konnte mittels 2D-NMR-Untersuchungen lokalisiert werden. In Kooperation mit der theoretischen Chemie sollte durch Berechnungen untersucht werden, wie die beobachteten Verbindungen entstehen. Durch eine auftretende Wechselwirkung innerhalb des Moleküls konnte allerdings keine explizite Aussage getroffen werden.
Im Anschluss sollten die erhaltenen Verbindungen in einer allylischen Oxidation zu Chalkonen umgesetzt werden. Die Ruthenium-katalysierten Methoden zeigten u. a. keine Eignung. Es konnte allerdings eine metallfreie, Mikrowellen-unterstützte Methode erfolgreich erprobt werden, sodass die Darstellung einiger Vertreter dieser physiologisch aktiven Stoffklasse gelang.
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.
Floods are among the most costly natural hazards that affect Europe and Germany, demanding a continuous adaptation of flood risk management. While social and economic development in recent years altered the flood risk patterns mainly with regard to an increase in flood exposure, different flood events are further expected to increase in frequency and severity in certain European regions due to climate change. As a result of recent major flood events in Germany, the German flood risk management shifted to more integrated approaches that include private precaution and preparation to reduce the damage on exposed assets. Yet, detailed insights into the preparedness decisions of flood-prone households remain scarce, especially in connection to mental impacts and individual coping strategies after being affected by different flood types.
This thesis aims to gain insights into flash floods as a costly hazard in certain German regions and compares the damage driving factors to the damage driving factors of river floods. Furthermore, psychological impacts as well as the effects on coping and mitigation behaviour of flood-affected households are assessed. In this context, psychological models such as the Protection Motivation Theory (PMT) and methods such as regressions and Bayesian statistics are used to evaluate influencing factors on the mental coping after an event and to identify psychological variables that are connected to intended private flood mitigation. The database consists of surveys that were conducted among affected households after major river floods in 2013 and flash floods in 2016.
The main conclusions that can be drawn from this thesis reveal that the damage patterns and damage driving factors of strong flash floods differ significantly from those of river floods due to a rapid flow origination process, higher flow velocities and flow forces. However, the effects on mental coping of people that have been affected by flood events appear to be weakly influenced by different flood types, but yet show a coherence to the event severity, where often thinking of the respective event is pronounced and also connected to a higher mitigation motivation. The mental coping and preparation after floods is further influenced by a good information provision and a social environment, which encourages a positive attitude towards private mitigation.
As an overall recommendation, approaches for an integrated flood risk management in Germany should be followed that also take flash floods into account and consider psychological characteristics of affected households to support and promote private flood mitigation. Targeted information campaigns that concern coping options and discuss current flood risks are important to better prepare for future flood hazards in Germany.
The central motivation of the thesis was to provide possible solutions and concepts to improve the performance (e.g. activity and selectivity) of electrochemical N2 reduction reaction (NRR). Given that porous carbon-based materials usually exhibit a broad range of structural properties, they could be promising NRR catalysts. Therefore, the advanced design of novel porous carbon-based materials and the investigation of their application in electrocatalytic NRR including the particular reaction mechanisms are the most crucial points to be addressed. In this regard, three main topics were investigated. All of them are related to the functionalization of porous carbon for electrochemical NRR or other electrocatalytic reactions.
In chapter 3, a novel C-TixOy/C nanocomposite has been described that has been obtained via simple pyrolysis of MIL-125(Ti). A novel mode for N2 activation is achieved by doping carbon atoms from nearby porous carbon into the anion lattice of TixOy. By comparing the NRR performance of M-Ts and by carrying out DFT calculations, it is found that the existence of (O-)Ti-C bonds in C-doped TixOy can largely improve the ability to activate and reduce N2 as compared to unoccupied OVs in TiO2. The strategy of rationally doping heteroatoms into the anion lattice of transition metal oxides to create active centers may open many new opportunities beyond the use of noble metal-based catalysts also for other reactions that require the activation of small molecules as well.
In chapter 4, a novel catalyst construction composed of Au single atoms decorated on the surface of NDPCs was reported. The introduction of Au single atoms leads to active reaction sites, which are stabilized by the N species present in NDPCs. Thus, the interaction within as-prepared AuSAs-NDPCs catalysts enabled promising performance for electrochemical NRR. For the reaction mechanism, Au single sites and N or C species can act as Frustrated Lewis pairs (FLPs) to enhance the electron donation and back-donation process to activate N2 molecules. This work provides new opportunities for catalyst design in order to achieve efficient N2 fixation at ambient conditions by utilizing recycled electric energy.
The last topic described in chapter 5 mainly focused on the synthesis of dual heteroatom-doped porous carbon from simple precursors. The introduction of N and B heteroatoms leads to the construction of N-B motives and Frustrated Lewis pairs in a microporous architecture which is also rich in point defects. This can improve the strength of adsorption of different reactants (N2 and HMF) and thus their activation. As a result, BNC-2 exhibits a desirable electrochemical NRR and HMF oxidation performance. Gas adsorption experiments have been used as a simple tool to elucidate the relationship between the structure and catalytic activity. This work provides novel and deep insights into the rational design and the origin of activity in metal-free electrocatalysts and enables a physically viable discussion of the active motives, as well as the search for their further applications.
Throughout this thesis, the ubiquitous problems of low selectivity and activity of electrochemical NRR are tackled by designing porous carbon-based catalysts with high efficiency and exploring their catalytic mechanisms. The structure-performance relationships and mechanisms of activation of the relatively inert N2 molecules are revealed by either experimental results or DFT calculations. These fundamental understandings pave way for a future optimal design and targeted promotion of NRR catalysts with porous carbon-based structure, as well as study of new N2 activation modes.
The natural abundance of Coiled Coil (CC) motifs in cytoskeleton and extracellular matrix proteins suggests that CCs play an important role as passive (structural) and active (regulatory) mechanical building blocks. CCs are self-assembled superhelical structures consisting of 2-7 α-helices. Self-assembly is driven by hydrophobic and ionic interactions, while the helix propensity of the individual helices contributes additional stability to the structure. As a direct result of this simple sequence-structure relationship, CCs serve as templates for protein design and sequences with a pre-defined thermodynamic stability have been synthesized de novo. Despite this quickly increasing knowledge and the vast number of possible CC applications, the mechanical function of CCs has been largely overlooked and little is known about how different CC design parameters determine the mechanical stability of CCs. Once available, this knowledge will open up new applications for CCs as nanomechanical building blocks, e.g. in biomaterials and nanobiotechnology.
With the goal of shedding light on the sequence-structure-mechanics relationship of CCs, a well-characterized heterodimeric CC was utilized as a model system. The sequence of this model system was systematically modified to investigate how different design parameters affect the CC response when the force is applied to opposing termini in a shear geometry or separated in a zipper-like fashion from the same termini (unzip geometry). The force was applied using an atomic force microscope set-up and dynamic single-molecule force spectroscopy was performed to determine the rupture forces and energy landscape properties of the CC heterodimers under study. Using force as a denaturant, CC chain separation is initiated by helix uncoiling from the force application points. In the shear geometry, this allows uncoiling-assisted sliding parallel to the force vector or dissociation perpendicular to the force vector. Both competing processes involve the opening of stabilizing hydrophobic (and ionic) interactions. Also in the unzip geometry, helix uncoiling precedes the rupture of hydrophobic contacts.
In a first series of experiments, the focus was placed on canonical modifications in the hydrophobic core and the helix propensity. Using the shear geometry, it was shown that both a reduced core packing and helix propensity lower the thermodynamic and mechanical stability of the CC; however, with different effects on the energy landscape of the system. A less tightly packed hydrophobic core increases the distance to the transition state, with only a small effect on the barrier height. This originates from a more dynamic and less tightly packed core, which provides more degrees of freedom to respond to the applied force in the direction of the force vector. In contrast, a reduced helix propensity decreases both the distance to the transition state and the barrier height. The helices are ‘easier’ to unfold and the remaining structure is less thermodynamically stable so that dissociation perpendicular to the force axis can occur at smaller deformations.
Having elucidated how canonical sequence modifications influence CC mechanics, the pulling geometry was investigated in the next step. Using one and the same sequence, the force application points were exchanged and two different shear and one unzipping geometry were compared. It was shown that the pulling geometry determines the mechanical stability of the CC. Different rupture forces were observed in the different shear as well as in the unzipping geometries, suggesting that chain separation follows different pathways on the energy landscape. Whereas the difference between CC shearing and unzipping was anticipated and has also been observed for other biological structures, the observed difference for the two shear geometries was less expected. It can be explained with the structural asymmetry of the CC heterodimer. It is proposed that the direction of the α-helices, the different local helix propensities and the position of a polar asparagine in the hydrophobic core are responsible for the observed difference in the chain separation pathways. In combination, these factors are considered to influence the interplay between processes parallel and perpendicular to the force axis.
To obtain more detailed insights into the role of helix stability, helical turns were reinforced locally using artificial constraints in the form of covalent and dynamic ‘staples’. A covalent staple bridges to adjacent helical turns, thus protecting them against uncoiling. The staple was inserted directly at the point of force application in one helix or in the same terminus of the other helix, which did not experience the force directly. It was shown that preventing helix uncoiling at the point of force application reduces the distance to the transition state while slightly increasing the barrier height. This confirms that helix uncoiling is critically important for CC chain separation. When inserted into the second helix, this stabilizing effect is transferred across the hydrophobic core and protects the force-loaded turns against uncoiling. If both helices were stapled, no additional increase in mechanical stability was observed. When replacing the covalent staple with a dynamic metal-coordination bond, a smaller decrease in the distance to the transition was observed, suggesting that the staple opens up while the CC is under load.
Using fluorinated amino acids as another type of non-natural modification, it was investigated how the enhanced hydrophobicity and the altered packing at the interface influences CC mechanics. The fluorinated amino acid was inserted into one central heptad of one or both α-helices. It was shown that this substitution destabilized the CC thermodynamically and mechanically. Specifically, the barrier height was decreased and the distance to the transition state increased. This suggests that a possible stabilizing effect of the increased hydrophobicity is overruled by a disturbed packing, which originates from a bad fit of the fluorinated amino acid into the local environment. This in turn increases the flexibility at the interface, as also observed for the hydrophobic core substitution described above. In combination, this confirms that the arrangement of the hydrophobic side chains is an additional crucial factor determining the mechanical stability of CCs.
In conclusion, this work shows that knowledge of the thermodynamic stability alone is not sufficient to predict the mechanical stability of CCs. It is the interplay between helix propensity and hydrophobic core packing that defines the sequence-structure-mechanics relationship. In combination, both parameters determine the relative contribution of processes parallel and perpendicular to the force axis, i.e. helix uncoiling and uncoiling-assisted sliding as well as dissociation. This new mechanistic knowledge provides insight into the mechanical function of CCs in tissues and opens up the road for designing CCs with pre-defined mechanical properties. The library of mechanically characterized CCs developed in this work is a powerful starting point for a wide spectrum of applications, ranging from molecular force sensors to mechanosensitive crosslinks in protein nanostructures and synthetic extracellular matrix mimics.
Force plays a fundamental role in the regulation of biological processes. Cells can sense the mechanical properties of the extracellular matrix (ECM) by applying forces and transmitting mechanical signals. They further use mechanical information for regulating a wide range of cellular functions, including adhesion, migration, proliferation, as well as differentiation and apoptosis. Even though it is well understood that mechanical signals play a crucial role in directing cell fate, surprisingly little is known about the range of forces that define cell-ECM interactions at the molecular level.
Recently, synthetic molecular force sensor (MFS) designs have been established for measuring the molecular forces acting at the cell-ECM interface. MFSs detect the traction forces generated by cells and convert this mechanical input into an optical readout. They are composed of calibrated mechanoresponsive building blocks and are usually equipped with a fluorescence reporter system. Up to date, many different MFS designs have been introduced and successfully used for measuring forces involved in the adhesion of mammalian cells. These MFSs utilize different molecular building blocks, such as double-stranded deoxyribonucleic acid (dsDNA) molecules, DNA hairpins and synthetic polymers like polyethylene glycol (PEG). These currently available MFS designs lack ECM mimicking properties.
In this work, I introduce a new MFS building block for cell biology applications, derived from the natural ECM. It combines mechanical tunability with the ability to mimic the native cellular microenvironment. Inspired by structural ECM proteins with load bearing function, this new MFS design utilizes coiled coil (CC)-forming peptides. CCs are involved in structural and mechanical tasks in the cellular microenvironment and many of the key protein components of the cytoskeleton and the ECM contain CC structures. The well-known folding motif of CC structures, an easy synthesis via solid phase methods and the many roles CCs play in biological processes have inspired studies to use CCs as tunable model systems for protein design and assembly. All these properties make CCs ideal candidates as building blocks for MFSs. In this work, a series of heterodimeric CCs were designed, characterized and further used as molecular building blocks for establishing a novel, next-generation MFS prototype.
A mechanistic molecular understanding of their structural response to mechanical load is essential for revealing the sequence-structure-mechanics relationships of CCs. Here, synthetic heterodimeric CCs of different length were loaded in shear geometry and their mechanical response was investigated using a combination of atomic force microscope (AFM)-based single-molecule force spectroscopy (SMFS) and steered molecular dynamics (SMD) simulations. SMFS showed that the rupture forces of short heterodimeric CCs (3-5 heptads) lie in the range of 20-50 pN, depending on CC length, pulling geometry and the applied loading rate (dF/dt). Upon shearing, an initial rise in the force, followed by a force plateau and ultimately strand separation was observed in SMD simulations. A detailed structural analysis revealed that CC response to shear load depends on the loading rate and involves helix uncoiling, uncoiling-assisted sliding in the direction of the applied force and uncoiling-assisted dissociation perpendicular to the force axis.
The application potential of these mechanically characterized CCs as building blocks for MFSs has been tested in 2D cell culture applications with the goal of determining the threshold force for cell adhesion. Fully calibrated, 4- to 5-heptad long, CC motifs (CC-A4B4 and CC-A5B5) were used for functionalizing glass surfaces with MFSs. 3T3 fibroblasts and endothelial cells carrying mutations in a signaling pathway linked to cell adhesion and mechanotransduction processes were used as model systems for time-dependent adhesion experiments. A5B5-MFS efficiently supported cell attachment to the functionalized surfaces for both cell types, while A4B4-MFS failed to maintain attachment of 3T3 fibroblasts after the first 2 hours of initial cell adhesion. This difference in cell adhesion behavior demonstrates that the magnitude of cell-ECM forces varies depending on the cell type and further supports the application potential of CCs as mechanoresponsive and tunable molecular building blocks for the development of next-generation protein-based MFSs.This novel CC-based MFS design is expected to provide a powerful new tool for observing cellular mechanosensing processes at the molecular level and to deliver new insights into the mechanisms and forces involved. This MFS design, utilizing mechanically tunable CC building blocks, will not only allow for measuring the molecular forces acting at the cell-ECM interface, but also yield a new platform for the development of mechanically controlled materials for a large number of biological and medical applications.
Emotions are a central element of human experience. They occur with high frequency in everyday life and play an important role in decision making. However, currently there is no consensus among researchers on what constitutes an emotion and on how emotions should be investigated. This dissertation identifies three problems of current emotion research: the problem of ground truth, the problem of incomplete constructs and the problem of optimal representation. I argue for a focus on the detailed measurement of emotion manifestations with computer-aided methods to solve these problems. This approach is demonstrated in three research projects, which describe the development of methods specific to these problems as well as their application to concrete research questions.
The problem of ground truth describes the practice to presuppose a certain structure of emotions as the a priori ground truth. This determines the range of emotion descriptions and sets a standard for the correct assignment of these descriptions. The first project illustrates how this problem can be circumvented with a multidimensional emotion perception paradigm which stands in contrast to the emotion recognition paradigm typically employed in emotion research. This paradigm allows to calculate an objective difficulty measure and to collect subjective difficulty ratings for the perception of emotional stimuli. Moreover, it enables the use of an arbitrary number of emotion stimuli categories as compared to the commonly used six basic emotion categories. Accordingly, we collected data from 441 participants using dynamic facial expression stimuli from 40 emotion categories. Our findings suggest an increase in emotion perception difficulty with increasing actor age and provide evidence to suggest that young adults, the elderly and men underestimate their emotion perception difficulty. While these effects were predicted from the literature, we also found unexpected and novel results. In particular, the increased difficulty on the objective difficulty measure for female actors and observers stood in contrast to reported findings. Exploratory analyses revealed low relevance of person-specific variables for the prediction of emotion perception difficulty, but highlighted the importance of a general pleasure dimension for the ease of emotion perception.
The second project targets the problem of incomplete constructs which relates to vaguely defined psychological constructs on emotion with insufficient ties to tangible manifestations. The project exemplifies how a modern data collection method such as face tracking data can be used to sharpen these constructs on the example of arousal, a long-standing but fuzzy construct in emotion research. It describes how measures of distance, speed and magnitude of acceleration can be computed from face tracking data and investigates their intercorrelations. We find moderate to strong correlations among all measures of static information on one hand and all measures of dynamic information on the other. The project then investigates how self-rated arousal is tied to these measures in 401 neurotypical individuals and 19 individuals with autism. Distance to the neutral face was predictive of arousal ratings in both groups. Lower mean arousal ratings were found for the autistic group, but no difference in correlation of the measures and arousal ratings could be found between groups. Results were replicated in a high autistic traits group consisting of 41 participants. The findings suggest a qualitatively similar perception of arousal for individuals with and without autism. No correlations between valence ratings and any of the measures could be found which emphasizes the specificity of our tested measures for the construct of arousal.
The problem of optimal representation refers to the search for the best representation of emotions and the assumption that there is a one-fits-all solution. In the third project we introduce partial least squares analysis as a general method to find an optimal representation to relate two high-dimensional data sets to each other. The project demonstrates its applicability to emotion research on the question of emotion perception differences between men and women. The method was used with emotion rating data from 441 participants and face tracking data computed on 306 videos. We found quantitative as well as qualitative differences in the perception of emotional facial expressions between these groups. We showed that women’s emotional perception systematically captured more of the variance in facial expressions. Additionally, we could show that significant differences exist in the way that women and men perceive some facial expressions which could be visualized as concrete facial expression sequences. These expressions suggest differing perceptions of masked and ambiguous facial expressions between the sexes. In order to facilitate use of the developed method by the research community, a package for the statistical environment R was written. Furthermore, to call attention to the method and its usefulness for emotion research, a website was designed that allows users to explore a model of emotion ratings and facial expression data in an interactive fashion.
This dissertation combines field and geochemical observations and analyses with numerical modeling to understand the formation of vein-hosted Sn-W ore in the Panasqueira deposit of Portugal, which is among the ten largest worldwide. The deposit is located above a granite body that is altered by magmatic-hydrothermal fluids in its upper part (greisen). These fluids are thought to be the source of metals, but that was still under debate. The goal of this study is to determine the composition and temperature of hydrothermal fluids at Panasqueira, and with that information to construct a numerical model of the hydrothermal system. The focus is on analysis of the minerals tourmaline and white mica, which formed during mineralization and are widespread throughout the deposit. Tourmaline occurs mainly in alteration zones around mineralized veins and is less abundant in the vein margins. White mica is more widespread. It is abundant in vein margins as well as alteration zones, and also occurs in the granite greisen. The laboratory work involved in-situ microanalysis of major- and trace elements in tourmaline and white mica, and boron-isotope analysis in both minerals by secondary ion mass spectrometry (SIMS).
The boron-isotope composition of tourmaline and white mica suggests a magmatic source. Comparison of hydrothermally-altered and unaltered rocks from drill cores shows that the ore metals (W, Sn, Cu, and Zn) and As, F, Li, Rb, and Cs were introduced during the alteration. Most of these elements are also enriched in tourmaline and mica, which confirms their potential value as exploration guides to Sn-W ores elsewhere.
The thermal evolution of the hydrothermal system was estimated by B-isotope exchange thermometry and the Ti-in-quartz method. Both methods yielded similar temperatures for the early hydrothermal phase: 430° to 460°C for B-isotopes and 503° ± 24°C for Ti-in-quartz. Mineral pairs from a late fault zone yield significantly lower median temperatures of 250°C. The combined results of thermometry with variations in chemical and B-isotope composition of tourmaline and mica suggest that a similar magmatic-hydrothermal fluid was active at all stages of mineralization. Mineralization in the late stage shows the same B-isotope composition as in the main stage despite a ca. 250°C cooling, which supports a multiple injection model of magmatic-hydrothermal fluids.
Two-dimensional numerical simulations of convection in a multiphase NaCl hydrothermal system were conducted: (a) in order to test a new approach (lower dimensional elements) for flow through fractures and faults and (b) in order to identify conditions for horizontal fluid flow as observed in the flat-lying veins at Panasqueira. The results show that fluid flow over an intrusion (heat and fluid source) develops a horizontal component if there is sufficient fracture connectivity. Late, steep fault zones have been identified in the deposit area, which locally contain low-temperature Zn-Pb mineralization. The model results confirm that the presence of subvertical faults with enhanced permeability play a crucial role in the ascent of magmatic fluids to the surface and the recharge of meteoric waters. Finally, our model results suggest that recharge of meteoric fluids and mixing processes may be important at later stages, while flow of magmatic fluids dominate the early stages of the hydrothermal fluid circulation.
Magmatic-hydrothermal fluids are responsible for numerous mineralization types, including porphyry copper and granite related tin-tungsten (Sn-W) deposits. Ore formation is dependent on various factors, including, the pressure and temperature regime of the intrusions, the chemical composition of the magma and hydrothermal fluids, and fluid rock interaction during the ascent. Fluid inclusions have potential to provide direct information on the temperature, salinity, pressure and chemical composition of fluids responsible for ore formation. Numerical modeling allows the parametrization of pluton features that cannot be analyzed directly via geological observations.
Microthermometry of fluid inclusions from the Zinnwald Sn-W deposit, Erzgebirge, Germany / Czech Republic, provide evidence that the greisen mineralization is associated with a low salinity (2-10 wt.% NaCl eq.) fluid with homogenization temperatures between 350°C and 400°C. Quartzes from numerous veins are host to inclusions with the same temperatures and salinities, whereas cassiterite- and wolframite-hosted assemblages with slightly lower temperatures (around 350°C) and higher salinities (ca. 15 wt. NaCl eq.). Further, rare quartz samples contained boiling assemblages consisting of coexisting brine and vapor phases. The formation of ore minerals within the greisen is driven by invasive fluid-rock interaction, resulting in the loss of complexing agents (Cl-) leading to precipitation of cassiterite. The fluid inclusion record in the veins suggests boiling as the main reason for cassiterite and wolframite mineralization. Ore and coexisting gangue minerals hosted different types of fluid inclusions where the beginning boiling processes are solely preserved by the ore minerals emphasizing the importance of microthermometry in ore minerals. Further, the study indicates that boiling as a precipitation mechanism can only occur in mineralization related to shallow intrusions whereas deeper plutons prevent the fluid from boiling and can therefore form tungsten mineralization in the distal regions.
The tin mineralization in the Hämmerlein deposit, Erzgebirge, Germany, occurs within a skarn horizon and the underlying schist. Cassiterite within the skarn contains highly saline (30-50 wt% NaCl eq.) fluid inclusions, with homogenization temperatures up to 500°C, whereas cassiterites from the schist and additional greisen samples contain inclusions of lower salinity (~5 wt% NaCl eq.) and temperature (between 350 and 400°C). Inclusions in the gangue minerals (quartz, fluorite) preserve homogenization temperatures below 350°C and sphalerite showed the lowest homogenization temperatures (ca. 200°C) whereby all minerals (cassiterite from schist and greisen, gangue minerals and sphalerite) show similar salinity ranges (2-5 wt% NaCl eq.). Similar trace element contents and linear trends in the chemistry of the inclusions suggest a common source fluid. The inclusion record in the Hämmerlein deposit documents an early exsolution of hot brines from the underlying granite which is responsible for the mineralization hosted by the skarn. Cassiterites in schist and greisen are mainly forming due to fluid-rock interaction at lower temperatures. The low temperature inclusions documented in the sphalerite mineralization as well as their generally low trace element composition in comparison to the other minerals suggests that their formation was induced by mixing with meteoric fluids.
Numerical simulations of magma chambers and overlying copper distribution document the importance of incremental growth by sills. We analyzed the cooling behavior at variable injection intervals as well as sill thicknesses. The models suggest that magma accumulation requires volumetric injection rates of at least 4 x 10-4 km³/y. These injection rates are further needed to form a stable magmatic-hydrothermal fluid plume above the magma chamber to ensure a constant copper precipitation and enrichment within a confined location in order to form high-grade ore shells within a narrow geological timeframe between 50 and 100 kyrs as suggested for porphyry copper deposits. The highest copper enrichment can be found in regions with steep temperature gradients, typical of regions where the magmatic-hydrothermal fluid meets the cooler ambient fluids.
Das Preußische Erbrecht in der Judikatur des Berliner Obertribunals in den Jahren 1836 bis 1865
(2019)
Die Dissertation befasst sich mit dem Allgemeinen Preußischen Landrecht von 1794 und der hierzu ergangenen Rechtsprechung des Berliner Obertribunals. Im Fokus der Untersuchung stehen die erbrechtlichen Regelungen des Landrechts und deren Anwendung sowie Auslegung in der Judikatur des höchsten preußischen Gerichts. Der Forschungsgegenstand ergibt sich aus dem im Landrecht kodifizierten speziellen Gesetzesverständnisses. Nach diesem sollte die Gesetzesauslegung durch die Rechtsprechung auf ein Minimum, nämlich die Auslegung allein anhand des Wortlauts der Regelung reduziert werden, um dem absolutistischen Regierungsanspruch der preußischen Monarchen, namentlich Friedrich des Großen, hinreichend Rechnung zu tragen. In diesem Kontext wird der Frage nachgegangen, inwieweit das preußische Obertribunal das im Landrecht statuierte „Auslegungsverbot“ beachtet hat und in welchen Fällen sich das Gericht von der Vorgabe emanzipierte und weitere Auslegungsmethoden anwendete und sich so eine unabhängige Rechtsprechung entwickeln konnte.
Die Arbeit gliedert sich in drei Hauptabschnitte. Im Anschluss an die Einleitung, in der zunächst die rechtshistorische Bedeutung des Landrechts und des Erbrechts sowie der Untersuchungsgegenstand umrissen werden, folgt die Darstellung der Entstehungsgeschichte des Landrechts und des Berliner Obertribunals.
Hieran schließt sich in einem dritten Abschnitt eine Analyse der erbrechtlichen Vorschriften des Landrechts an. In dieser wird auf die Entstehungsgeschichte der verschiedenen erbrechtlichen Institute wie beispielsweise der gesetzlichen und gewillkürten Erbfolge, dem Pflichtteilsrecht etc., unter Berücksichtigung des zeitgenössischen wissenschaftlichen Diskurses eingegangen.
Im vierten Abschnitt geht es um die Judikate des Berliner Obertribunals aus den Jahren 1836-1865 in denen die zuvor dargestellten erbrechtlichen Regelungen entscheidungserheblich waren. Dabei wird der Forschungsfrage, inwieweit das Obertribunal das im Landrecht statuierte Auslegungsverbot beachtet hat und in welchen Fällen es von diesem abwich bzw. weitere Auslegungsmethoden anwendete, konkret nachgegangen wird. Insgesamt werden 26 Entscheidungen des Obertribunals unter dem Aspekt der Auslegungspraxis, der Kontinuität und der Beschleunigung der Rechtsprechung analysiert und ausgewertet.
Since half a century, cytometry has been a major scientific discipline in the field of cytomics - the study of system’s biology at single cell level. It enables the investigation of physiological processes, functional characteristics and rare events with proteins by analysing multiple parameters on an individual cell basis. In the last decade, mass cytometry has been established which increased the parallel measurement to up to 50 proteins. This has shifted the analysis strategy from conventional consecutive manual gates towards multi-dimensional data processing. Novel algorithms have been developed to tackle these high-dimensional protein combinations in the data. They are mainly based on clustering or non-linear dimension reduction techniques, or both, often combined with an upstream downsampling procedure. However, these tools have obstacles either in comprehensible interpretability, reproducibility, computational complexity or in comparability between samples and groups.
To address this bottleneck, a reproducible, semi-automated cytometric data mining workflow PRI (pattern recognition of immune cells) is proposed which combines three main steps: i) data preparation and storage; ii) bin-based combinatorial variable engineering of three protein markers, the so called triploTs, and subsequent sectioning of these triploTs in four parts; and iii) deployment of a data-driven supervised learning algorithm, the cross-validated elastic-net regularized logistic regression, with these triploT sections as input variables. As a result, the selected variables from the models are ranked by their prevalence, which potentially have discriminative value. The purpose is to significantly facilitate the identification of meaningful subpopulations, which are most distinguish between two groups. The proposed workflow PRI is exemplified by a recently published public mass cytometry data set. The authors found a T cell subpopulation which is discriminative between effective and ineffective treatment of breast carcinomas in mice. With PRI, that subpopulation was not only validated, but was further narrowed down as a particular Th1 cell population. Moreover, additional insights of combinatorial protein expressions are revealed in a traceable manner. An essential element in the workflow is the reproducible variable engineering. These variables serve as basis for a clearly interpretable visualization, for a structured variable exploration and as input layers in neural network constructs.
PRI facilitates the determination of marker levels in a semi-continuous manner. Jointly with the combinatorial display, it allows a straightforward observation of correlating patterns, and thus, the dominant expressed markers and cell hierarchies. Furthermore, it enables the identification and complex characterization of discriminating subpopulations due to its reproducible and pseudo-multi-parametric pattern presentation. This endorses its applicability as a tool for unbiased investigations on cell subsets within multi-dimensional cytometric data sets.
Medical imaging plays an important role in disease diagnosis, treatment planning, and clinical monitoring. One of the major challenges in medical image analysis is imbalanced training data, in which the class of interest is much rarer than the other classes. Canonical machine learning algorithms suppose that the number of samples from different classes in the training dataset is roughly similar or balance. Training a machine learning model on an imbalanced dataset can introduce unique challenges to the learning problem.
A model learned from imbalanced training data is biased towards the high-frequency samples. The predicted results of such networks have low sensitivity and high precision. In medical applications, the cost of misclassification of the minority class could be more than the cost of misclassification of the majority class. For example, the risk of not detecting a tumor could be much higher than referring to a healthy subject to a doctor. The current Ph.D. thesis introduces several deep learning-based approaches for handling class imbalanced problems for learning multi-task such as disease classification and semantic segmentation.
At the data-level, the objective is to balance the data distribution through re-sampling the data space: we propose novel approaches to correct internal bias towards fewer frequency samples. These approaches include patient-wise batch sampling, complimentary labels, supervised and unsupervised minority oversampling using generative adversarial networks for all.
On the other hand, at algorithm-level, we modify the learning algorithm to alleviate the bias towards majority classes. In this regard, we propose different generative adversarial networks for cost-sensitive learning, ensemble learning, and mutual learning to deal with highly imbalanced imaging data.
We show evidence that the proposed approaches are applicable to different types of medical images of varied sizes on different applications of routine clinical tasks, such as disease classification and semantic segmentation. Our various implemented algorithms have shown outstanding results on different medical imaging challenges.
Light-switchable proteins are being used increasingly to understand and manipulate complex molecular systems. The success of this approach has fueled the development of tailored photo-switchable proteins, to enable targeted molecular events to be studied using light. The development of novel photo-switchable tools has to date largely relied on rational design. Complementing this approach with directed evolution would be expected to facilitate these efforts. Directed evolution, however, has been relatively infrequently used to develop photo-switchable proteins due to the challenge presented by high-throughput evaluation of switchable protein activity. This thesis describes the development of two genetic circuits that can be used to evaluate libraries of switchable proteins, enabling optimization of both the on- and off-states. A screening system is described, which permits detection of DNA-binding activity based on conditional expression of a fluorescent protein. In addition, a tunable selection system is presented, which allows for the targeted selection of protein-protein interactions of a desired affinity range. This thesis additionally describes the development and characterization of a synthetic protein that was designed to investigate chromophore reconstitution in photoactive yellow protein (PYP), a promising scaffold for engineering photo-controlled protein tools.
Earthquake swarms are characterized by large numbers of events occurring in a short period of time within a confined source volume and without significant mainshock aftershock pattern as opposed to tectonic sequences. Intraplate swarms in the absence of active volcanism usually occur in continental rifts as for example in the Eger Rift zone in North West Bohemia, Czech Republic. A common hypothesis links event triggering to pressurized fluids. However, the exact causal chain is often poorly understood since the underlying geotectonic processes are slow compared to tectonic sequences. The high event rate during active periods challenges standard seismological routines as these are often designed for single events and therefore costly in terms of human resources when working with phase picks or computationally costly when exploiting full waveforms.
This methodological thesis develops new approaches to analyze earthquake swarm seismicity as well as the underlying seismogenic volume. It focuses on the region of North West (NW) Bohemia, a well studied, well monitored earthquake swarm region.
In this work I develop and test an innovative approach to detect and locate earthquakes using deep convolutional neural networks. This technology offers great potential as it allows to efficiently process large amounts of data which becomes increasingly important given that seismological data storage grows at increasing pace. The proposed deep neural network trained on NW Bohemian earthquake swarm records is able to locate 1000 events in less than 1 second using full waveforms while approaching precision of double difference relocated catalogs. A further technological novelty is that the trained filters of the deep neural network’s first layer can be repurposed to function as a pattern matching event detector without additional training on noise datasets. For further methodological development and benchmarking, I present a new toolbox to generate realistic earthquake cluster catalogs as well as synthetic full waveforms of those clusters in an automated fashion. The input is parameterized using constraints on source volume geometry, nucleation and frequency-magnitude relations. It harnesses recorded noise to produce highly realistic synthetic data for benchmarking and development. This tool is used to study and assess detection performance in terms of magnitude of completeness Mc of a full waveform detector applied to synthetic data of a hydrofracturing experiment at the Wysin site, Poland.
Finally, I present and demonstrate a novel approach to overcome the masking effects of wave propagation between earthquake and stations and to determine source volume attenuation directly in the source volume where clustered earthquakes occur. The new event couple spectral ratio approach exploits high frequency spectral slopes of two events sharing the greater part of their rays. Synthetic tests based on the toolbox mentioned before show that this method is able to infer seismic wave attenuation within the source volume at high spatial resolution. Furthermore, it is independent from the distance towards a station as well as the complexity of the attenuation and velocity structure outside of the source volume of swarms. The application to recordings of the NW Bohemian earthquake swarm shows increased P phase attenuation within the source volume (Qp < 100) based on results at a station located close to the village Luby (LBC). The recordings of a station located in epicentral proximity, close to Nový Kostel (NKC), show a relatively high complexity indicating that waves arriving at that station experience more scattering than signals recorded at other stations. The high level of complexity destabilizes the inversion. Therefore, the Q estimate at NKC is not reliable and an independent proof of the high attenuation finding given the geometrical and frequency constraints is still to be done. However, a high attenuation in the source volume of NW Bohemian swarms has been postulated before in relation to an expected, highly damaged zone bearing CO 2 at high pressure.
The methods developed in the course of this thesis yield the potential to improve our understanding regarding the role of fluids and gases in intraplate event clustering.
Die Anfechtbarkeit und die Feststellbarkeit der Mutterschaft de lege lata und de lege ferenda
(2019)
Der althergebrachte Grundsatz, wonach das Kind von der Frau abstammt, welche es geboren hat, ist durch die moderne Fortpflanzungsmedizin ins Wanken geraten. Dennoch ordnet § 1591 BGB das Kind unanfechtbar der Geburtsmutter zu. Rechtliche und genetische Mutterschaft fallen deshalb dauerhaft auseinander, wenn das Kind im Wege der Leihmutterschaft oder nach einer Eizell- bzw. Embryospende zur Welt kommt. Die auf diese Methoden der artifiziellen Reproduktion bezogenen, im Inland bestehenden Verbote halten Paare mit Kinderwunsch nicht davon ab, auf entsprechende Angebote im Ausland zurückzugreifen. Daraus resultierende kollisions- und verfassungsrechtliche Probleme sind Gegenstand der vorliegenden Arbeit.
Für den Bereich der Leihmutterschaft wird der Frage nachgegangen, ob die mit dem Anfechtungsausschluss verfolgten Ziele des Gesetzgebers die damit einhergehenden Beeinträchtigungen grundrechtlich geschützter Rechtspositionen von genetischer Mutter und Kind rechtfertigen können. Besonderes Augenmerk liegt auf dem von Art. 6 Abs. 2 S. 1 GG geschützten Interesse von leiblichen Eltern und Kindern, die verfahrensrechtliche Möglichkeit zu erhalten, rechtlich einander zugeordnet zu werden. Dieses Interesse wird den Zielen des Gesetzgebers, der mit dem Anfechtungsausschluss die Rechte von Leihmüttern und Kindern zu schützen beabsichtigt, im Rahmen einer umfassenden Verhältnismäßigkeitsprüfung gegenübergestellt.
In den Konstellationen der Eizell- und Embryospende tritt schwerpunktmäßig das Recht des Kindes auf Kenntnis der eigenen Abstammung in den Vordergrund und mit ihm die Frage, ob sich daraus eine Verpflichtung des Gesetzgebers ableiten lässt, den Tatbestand von § 1598a BGB so zu erweitern, dass die vermuteten genetischen Eltern für den Bereich der artifiziellen Reproduktion in den Kreis der Klärungsverpflichteten aufgenommen werden.
Neben diesen Schwerpunkten werden viele weitere Probleme angesprochen. Im Ergebnis mündet die Arbeit in einen Vorschlag für die Legislative.
In this thesis we introduce the concept of the degree of formality. It is directed against a dualistic point of view, which only distinguishes between formal and informal proofs. This dualistic attitude does not respect the differences between the argumentations classified as informal and it is unproductive because the individual potential of the respective argumentation styles cannot be appreciated and remains untapped.
This thesis has two parts. In the first of them we analyse the concept of the degree of formality (including a discussion about the respective benefits for each degree) while in the second we demonstrate its usefulness in three case studies. In the first case study we will repair Haskell B. Curry's view of mathematics, which incidentally is of great importance in the first part of this thesis, in light of the different degrees of formality. In the second case study we delineate how awareness of the different degrees of formality can be used to help students to learn how to prove. Third, we will show how the advantages of proofs of different degrees of formality can be combined by the development of so called tactics having a medium degree of formality. Together the three case studies show that the degrees of formality provide a convincing solution to the problem of untapped potential.
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.
One method of embedding groups into skew fields was introduced by A. I. Mal'tsev and B. H. Neumann (cf. [18, 19]). If G is an ordered group and F is a skew field, the set F((G)) of formal power series over F in G with well-ordered support forms a skew field into which the group ring F[G] can be embedded. Unfortunately it is not suficient that G is left-ordered since F((G)) is only an F-vector space in this case as there is no natural way to define a multiplication on F((G)). One way to extend the original idea onto left-ordered groups is to examine the endomorphism ring of F((G)) as explored by N. I. Dubrovin (cf. [5, 6]). It is possible to embed any crossed product ring F[G; η, σ] into the endomorphism ring of F((G)) such that each non-zero element of F[G; η, σ] defines an automorphism of F((G)) (cf. [5, 10]). Thus, the rational closure of F[G; η, σ] in the endomorphism ring of F((G)), which we will call the Dubrovin-ring of F[G; η, σ], is a potential candidate for a skew field of fractions of F[G; η, σ]. The methods of N. I. Dubrovin allowed to show that specific classes of groups can be embedded into a skew field. For example, N. I. Dubrovin contrived some special criteria, which are applicable on the universal covering group of SL(2, R). These methods have also been explored by J. Gräter and R. P. Sperner (cf. [10]) as well as N.H. Halimi and T. Ito (cf. [11]). Furthermore, it is of interest to know if skew fields of fractions are unique. For example, left and right Ore domains have unique skew fields of fractions (cf. [2]). This is not the general case as for example the free group with 2 generators can be embedded into non-isomorphic skew fields of fractions (cf. [12]). It seems likely that Ore domains are the most general case for which unique skew fields of fractions exist. One approach to gain uniqueness is to restrict the search to skew fields of fractions with additional properties. I. Hughes has defined skew fields of fractions of crossed product rings F[G; η, σ] with locally indicable G which fulfill a special condition. These are called Hughes-free skew fields of fractions and I. Hughes has proven that they are unique if they exist [13, 14]. This thesis will connect the ideas of N. I. Dubrovin and I. Hughes. The first chapter contains the basic terminology and concepts used in this thesis. We present methods provided by N. I. Dubrovin such as the complexity of elements in rational closures and special properties of endomorphisms of the vector space of formal power series F((G)). To combine the ideas of N.I. Dubrovin and I. Hughes we introduce Conradian left-ordered groups of maximal rank and examine their connection to locally indicable groups. Furthermore we provide notations for crossed product rings, skew fields of fractions as well as Dubrovin-rings and prove some technical statements which are used in later parts. The second chapter focuses on Hughes-free skew fields of fractions and their connection to Dubrovin-rings. For that purpose we introduce series representations to interpret elements of Hughes-free skew fields of fractions as skew formal Laurent series. This 1 Introduction allows us to prove that for Conradian left-ordered groups G of maximal rank the statement "F[G; η, σ] has a Hughes-free skew field of fractions" implies "The Dubrovin ring of F [G; η, σ] is a skew field". We will also prove the reverse and apply the results to give a new prove of Theorem 1 in [13]. Furthermore we will show how to extend injective ring homomorphisms of some crossed product rings onto their Hughes-free skew fields of fractions. At last we will be able to answer the open question whether Hughes--free skew fields are strongly Hughes-free (cf. [17, page 53]).