Well-posedness of a bulk-surface convective Cahn–Hilliard system with dynamic boundary conditions

We consider a general class of bulk-surface convective Cahn–Hilliard systems with dynamic boundary conditions. In contrast to classical Neumann boundary conditions, the dynamic boundary conditions of Cahn–Hilliard type allow for dynamic changes of the contact angle between the diffuse interface and the boundary, a convection-induced motion of the contact line as well as absorption of material by the boundary. The coupling conditions for bulk and surface quantities involve parameters K,L ∈ [0,∞], whose choice declares whether these conditions are of Dirichlet, Robin or Neumann type. We first prove the existence of a weak solution to our model in the case K,L ∈ (0,∞) by means of a Faedo–Galerkin approach. For all other cases, the existence of a weak solution is then shown by means of the asymptotic limits, where K and L are sent to zero or to infinity, respectively. Eventually, we establish higher regularity for the phase-fields, and we prove the uniqueness of weak solutions given that the mobility functions are constant

Verkürzte Mikroemboliedetektion bei Verdacht auf Endokarditis - eine Pilotstudie

Eine gefürchtete Komplikation der Erkrankung Endokarditis, insbesondere der infektiösen Endokarditis, stellt die Emboliegenität dar. Daraus resultiert ein hohes Risiko, im Verlauf dieser Krankheit, einen Schlaganfall zu erleiden, weshalb die Diagnose zeitnah gestellt werden sollte, um möglichst schnell und gezielt eine geeignete Therapie zu gewährleisten. Beim Verdacht auf eine Endokarditis stehen zur frühzeitigen Diagnostik verschiedene Techniken zur Verfügung, die jedoch zum Teil Nachteile, zeitliche Verzögerungen für den Patienten mit sich bringen oder eine zu geringe Sensitivität bzw. Spezifität besitzen. In der vorliegenden Dissertation wurde daher untersucht, ob der Einsatz der Mikroemboliedetektion mittels einer mobilen transkraniellen Duplexsonographie (TCCS/ TCD) über einen Zeitraum von nur zehn Minuten als ein schnelles und sicheres Verfahren die Verdachtsdiagnose einer Endokarditis stützen kann. Die dazu an insgesamt 33 Patienten durchgeführte verkürzte Mikroemboliedetektion mittels TCD ergab jedoch keinen eindeutig signifikanten Zusammenhang zwischen der Messung von Mikroembolien und dem Vorliegen einer Endokarditis. Bezieht man allerdings das zusätzlich retrospektiv aufgenommene Patientengut mit ein, lässt sich eine eindeutige Tendenz zu einem häufigeren Auftreten von detektierbaren MES im Rahmen einer Endokarditis erkennen. Zusammenfassend lässt sich sagen, dass diese Mikroembolidetektion mithilfe der TCD durchaus Vorteile mit sich bringen und gerade bei Hochrisikopatienten angewendet werden könnte, um schneller den Verdacht auf eine Endokarditis erhärten zu können - weitere Studien mit einer größeren Stoffmenge vorausgesetzt

Reconstructing Disease Histories in Huge Discrete State Spaces

Many progressive diseases develop unnoticed and insidiously at the beginning. This leads to an observational gap, since the first data on the disease can only be obtained after diagnosis. Mutual Hazard Networks address this gap by reconstructing latent disease dynamics. They model the disease as a Markov chain on the space of all possible combinations of progression events. This space can be huge: Given a set of events, its size exceeds the number of atoms in the universe. Mutual Hazard Networks combine time-to-event modeling with generalized probabilistic graphical models, regularization, and modern numerical tensor formats to enable efficient calculations in large state spaces using compressed data formats. Here we review Mutual Hazard Networks and put them in the context of machine learning theory. We describe how the Mutual Hazard assumption leads to a compact parameterization of the models and show how modern tensor formats allow for efficient computations in large state spaces. Finally, we show how Mutual Hazard Networks reconstruct the most likely history of glioblastomas

D-2-hydroxyglutarate supports a tolerogenic phenotype with lowered major histocompatibility class II expression in non-malignant dendritic cells and acute myeloid leukemia cells

D-2-hydroxyglutarate (D-2-HG) accumulates in primary acute myeloid leukemia (AML) patients with mutated isocitrate dehydrogenase (IDH) and other malignancies. D-2-HG suppresses antitumor T cell immunity but little is known about potential effects on non-malignant myeloid cells. Here we show that D-2-HG impairs human but not murine dendritic cell (DC) differentiation, resulting in a tolerogenic phenotype with low major histocompatibility (MHC) class II expression. In line, IDH-mutated AML blasts exhibited lower expression of HLA-DP and were less susceptible to lysis by HLA-DP-specific T cells. Interestingly, D-2-HG reprogrammed metabolism towards increased lactate production in DCs and AML besides its expected impact on DNA demethylation. Vitamin C accelerated DNA demethylation, but only the combination of vitamin C and glycolytic inhibition lowered lactate levels and supported MHC class II expression. Our results indicate an unexpected link between the immunosuppressive metabolites 2-HG and lactic acid and suggest a potentially novel therapeutic strategy with combinations of anti-glycolytic drugs and epigenetic modulators (hypomethylating agents) or other therapeutics for the treatment of AML

Asymmetric Hydrofunctionalisation Reactions Catalysed by 3d Transition Metal Complexes or Main Group Element Compounds

This thesis primarily reports on the synthesis and catalytic activity of main group and 3d transition metal-based complexes in hydrofunctionalisation reactions. Chapter 1 gives an overview of enantioselective (transfer) hydrogenation, hydroboration and hydrosilylation reactions. In Chapter 2 the catalytic activity of phosphacyclohexadienyl anions is compared with organolithium reagents and alkoxides in hydroboration reactions. Chapter 3 reports the synthesis of magnesium complexes bearing chiral β ketiminate ligands and their activity and selectivity in enantioselective hydrofunctionalisation reactions. Chapter 4 describes the use of chiral bis(aryl)acenaphthenequinonediimines (BIANs) as ligands in the 3d transition metal catalysed enantioselective transfer hydrogenation of olefins. Chapter 5 covers the synthesis of cobaltate phosphinine complexes featuring rare or novel coordination modes of the phosphinine. Finally, Chapter 6 gives a summary of the results described in this thesis and provides a short outlook on asymmetric hydrofunctionalisation reactions

Untersuchung des Sitzverhaltens bei Mitarbeitenden eines großen Unternehmens und Erstellung eines zielgruppenspezifischen Maßnahmenkatalogs zur Sitzzeitprävention

Die Doktorarbeit beschäftigt sich mit den negativen Auswirkungen von sedentärem Verhalten. In Kombination mit einem Überangebot an hochkalorischen Nahrungsmitteln, wie er in vielen Ländern vorherrscht, ist das „Sedentary Behaviour“ verantwortlich für eine hohe Zahl an Gesundheitsschäden. Ziel der Arbeit ist eine Analyse des durchschnittlichen Sitzanteils an einem gewöhnlichen Arbeitstag bzw. der Sitzgewohnheiten im weiteren Sinne einer repräsentativen Gruppe, in diesem Fall Angestellte der Firma Infineon. Zu diesem Zweck wurde ein Fragenkatalog entwickelt und an 2500 Mitarbeitern von Infineon ausgegeben. Ein hoher Anteil der Studienteilnehmenden verbringen den Arbeitstag überwiegend sedentär, d.h. in sitzender Haltung mit nur wenigen Unterbrechungen. Angesichts dieser Daten ist der Bedarf an weiterer Aufklärung und Interventionen zur Reduzierung der Sitzzeit hoch

Data archive of "Is Task Switching Avoided to Save Effort or Time? Shorter Intertrial Durations Following Task Switches Increase the Willingness to Switch Tasks"

Data archive with coding sheet and raw data for Experiments 1 and 2

Synthesis of Novel Heterocyclic Compounds for Red and Green Triplet Matrix Materials for OLED Application

In the past years, enormous progress has been achieved in the development of materials for OLED application. The development of more efficient, less energy consuming, and durable devices is of high importance for the progress and sustainability in electronics. In this thesis, the synthesis of novel red and green triplet matrix materials (TMM’s) is described, and structure-property relationships are investigated by the systematic exchange of electron and hole conducting and linking subunits. In this context, a variety of differently constituted heteroaromatic trisubstituted benzofuropyrimidine/triphenyltriazine and carbazole derivatives were designed, synthesized, and tested. The influence of the triplet and HOMO/LUMO energy level and structure were evaluated regarding the lifetime, efficiency, and driving voltage. The first part of this work focuses on theoretical pre-evaluations by DFT, which led to the hypothesis, that benzofuropyrimidine is an attractive alternative to triphenyltriazine. The second part of this work focuses on the synthesis of heteroaromatic building blocks based on benzofuropyrimidine/triphenyltriazine and benzocarbazoles. Here, the selective benzocarbazole formation was investigated. Furthermore, the synthesis of a trisubstituted benzofuropyrimidine building block was established. The third part of this thesis focuses on the coupling of the above-mentioned synthesized building blocks to give red and green TMM’s respectively. The fourth part of this thesis deals with the evaluation of the synthesized molecules by electrochemical, thermal and photophysical experiments (CV, DSC, UV/Vis and fluorescence spectroscopy) as well as their performance in OLED stacks (EQE, lifetime and driving voltage). Interestingly, [c]-annulated and [b]-annulated benzocarbazole regioisomeric materials showed significant differences in their properties. The studies for green TMM’s showed, that benzofuropyrimidine in the electron accepting unit improves the lifetime compared to triazines, linking units improve voltage. Efficiency is good for all synthesized TMM’s. For red TMM’s, triazines provide better results in terms of efficiency and voltage. In the last part of this work, a photo-redox catalytic cyanoarene-nickel system was tested for the synthesis of TMM precursors. The electrophiles were identified to be the main limiting factor as its electronics as well as sterics can influence the outcome of the C-N coupling. Steric hinderance of naphthyl electrophiles provided low yields, while phenyl electrophiles showed good coupling outcomes. Electron-poor electrophiles reacted better than electron-rich electrophiles. The developed methodologies broaden the toolbox for the synthesis of TMM’s or precursors. The investigated structure-property relationships will further help develop and optimize properties of TMM’s

Brain stars take the lead during critical periods of early postnatal brain development: relevance of astrocytes in health and mental disorders

In the brain, astrocytes regulate shape and functions of the synaptic and vascular compartments through a variety of released factors and membrane-bound proteins. An imbalanced astrocyte activity can therefore have drastic negative impacts on brain development, leading to the onset of severe pathologies. Clinical and pre-clinical studies show alterations in astrocyte cell number, morphology, molecular makeup and astrocyte-dependent processes in different affected brain regions in neurodevelopmental (ND) and neuropsychiatric (NP) disorders. Astrocytes proliferate, differentiate and mature during the critical period of early postnatal brain development, a time window of elevated glia-dependent regulation of a proper balance between synapse formation/elimination, which is pivotal in refining synaptic connectivity. Therefore, any intrinsic and/or extrinsic factors altering these processes during the critical period may result in an aberrant synaptic remodeling and onset of mental disorders. The peculiar bridging position of astrocytes between synaptic and vascular compartments further allows them to “compute” the brain state and consequently secrete factors in the bloodstream, which may serve as diagnostic biomarkers of distinct healthy or disease conditions. Here, we collect recent advancements regarding astrogenesis and astrocyte-mediated regulation of neuronal network remodeling during early postnatal critical periods of brain development, focusing on synapse elimination. We then propose alternative hypotheses for an involvement of aberrancies in these processes in the onset of ND and NP disorders. In light of the well-known differential prevalence of certain brain disorders between males and females, we also discuss putative sex-dependent influences on these neurodevelopmental events. From a translational perspective, understanding age- and sex-dependent astrocyte-specific molecular and functional changes may help to identify biomarkers of distinct cellular (dys)functions in health and disease, favouring the development of diagnostic tools or the selection of tailored treatment options for male/female patients