12033 research outputs found
Sort by
In vitro Charakterisierung der antiproliferativen Wirksamkeit von nicht-invasivem physikalischem Plasma (NIPP: Non invasive physical plasma) in den drei gynäkologischen Malignitäten Leiomyosarkom (SK-UT-1), Mammakarzinom (MCF-7 und MDA-MB- 231) und Endometriumkarzinom (MFE-296)
Get PDFDie bösartige Neoplasie der Brustdrüse ist die häufigste Todesursache bei Frauen zwischen dem 35. und 55. LJ. Das EC betrifft am häufigsten postmenopausale Frauen, um das Alter von 68 Jahren. Mit einer Inzidenz in Deutschland von 10 900/Jahr und eine Rate von 41% aller Genitaltumore, bildet das EC die häufigste gynäkologische Neoplasie. Das Leiomyosarkom gehört zu den nicht-epithelialen Tumoren und kommt überall vor, wo glatte Muskulatur zu finden ist. Mit einer Häufigkeit von 63% stellt das uterine LMS das häufigste Sarkom des Corpus uteri. NIPP hat seit 1970 eine Anwendung in der Medizin gefunden. Sei es zur aseptischen Wundheilung in der Dermatologie, zur Dekontamination in der Hygiene oder zur Heilung komplizierter Kraniofaszialer Traumata in der Mund-Kiefer-Gesichtschirurgie. Aktuell wird der Einsatz von NIPP in der Onkologie angestrebt. Hier unterscheidet man zwischen der direkten und indirekten Plasmabehandlung. Während der direkten Behandlung (direkte NIPP-Exposition) ein operatives Setting als Voraussetzung braucht, hat die indirekte Behandlung den großen Vorteil konservative Heilungschancen anzubieten. Für all diese Tumoren ist häufig eine Kombination zwischen konservativen Therapien (i.S. einer Chemotherapie) und operativen Verfahren (Hysterektomie beim uLMS) die einzige mögliche Therapieoptionen. Diese schließt automatisch schwer erkrankt oder multimorbiden Patientinnen aus. Die NIPP-Behandlung zeigt ein antiproliferativ vielversprechendes Model und hat mehrfach nachgewiesen, dass gesundes Gewebe intakt bleibt. Eigene Daten haben sowohl bei der direkten als auch indirekten Behandlung gezeigt, dass nach zunehmender Behandlungsdauer eine stärkere antiproliferative Wirkung zu sehen war
Describing God? : Christian and Muslim Approaches to the Divine Attributes in Dialogue
No full textThis volume engages traditional and contemporary approaches to the Divine attributes in Christian-Muslim dialogue. A particular focus lies on the attributes of omnipotence and omniscience, justice and mercy, as well as simplicity and divine action. Engaging these attributes comparatively, two questions are posed: How can these attributes be conceived today, and to what extent is a mutual learning across religious traditions possible? Thereby, a special focus is placed on the role of analytic philosophy. How do the philosopical 'language games' used contribute to communicability across religions
State-Specific Density Functional Theory for Computational Screening of Organic Optoelectronic Materials
Get PDFIn recent years, organic light-emitting diodes (OLED) have rapidly grown in relevance due to their high color purity, mechanical flexibility, and energy efficiency, making them attractive options for applications in the display industry. For the design process of OLEDs, the computational modeling of the electronically excited-state properties of emitters devices has become an crucial part of the research and development pipeline. This thesis addresses the limitations and challenges associated with emitter modeling via common computational methods, i.e., time-dependent density functional theory (TD-DFT), by presenting alternative state-specific excited-state ΔSCF approaches within the framework of density functional theory (DFT). Specifically, I investigate the unrestricted open-shell and two-determinant restricted open-shell Kohn-Sham methods, herein called ΔUKS and ΔROKS respectively, for their accuracy in calculating singlet-triplet (ST) energy gaps and fluorescence energies in three different classes of emitters, namely donor-acceptor thermally activated delayed fluorescence (DA-TADF), multiresonance TADF (MR-TADF), and inverted singlet-triplet gap (INVEST) systems.
Starting with DA-TADF emitters, I compiled a new and diverse benchmark set of 27 TADF emitters, for which very accurate experimental ST gap references were available. Despite the fact that the charge-transfer (CT) states in DA-TADF emitters are notoriously difficult to model, due to the difficulties of capturing orbital relaxation and solvation effects, both ΔUKS and ΔROKS combined with a standard polarizable continuum model (PCM) achieved sub-chemical accuracy in the reproduction of experimental ST gaps. I additionally tested both ΔDFT approaches for reproducing experimental fluorescence energies in the STGABS27 benchmark set. Both ΔUKS and ΔROKS in combination with a nonequilibrium PCM for modeling solvation effects produce fluorescence energies close to experiment, better than TD-DFT.
The robustness of ΔDFT approaches for challenging systems encouraged me to examine the special class of INVEST emitters which feature an inversion of the singlet-triplet energy gap. To assess the capabilities of ΔDFT methods, I compiled two partially new benchmark sets: the smaller INVEST15 benchmark for testing different ΔDFT methods and establishing an accurate reference method, and the larger NAH159 benchmark, for validating the best-performing ΔDFT on a more diverse set. On both benchmark sets ΔUKS established itself as the superior ΔDFT approach, being able to not only qualitatively but also quantitatively reproduce high-level WFT reference results.
Finally, I investigate the performance of ΔDFT approaches for ST gaps and fluorescence energies of MR-TADF emitters. On a literature benchmark of 35 MR-TADF emitters with experimental references, the accuracy of computed ST gaps was in strong favor for ΔUKS compared to ΔROKS yet again, cementing ΔUKS as the more reliable and robust state-specific excited-state method. ΔUKS-calculated ST gaps reached chemical accuracy against experimental data, whereas ΔROKS failed to accurately reproduce trends in the benchmark set. For fluorescence energies of MR-TADF emitters, both ΔUKS and ΔROKS performed well, with a slight edge in accuracy towards ΔUKS. An particularly important development from this work is the density functional, FX175-ωPBE, which in combination with ΔUKS displays excellent accuracy for ST gaps and fluorescence energies across all tested benchmark set. Overall, the presented work establishes ΔDFT methods, foremost ΔUKS, as a valuable computational tool for the calculation and modeling of photophysical properties, enabling efficient and accurate screening of optoelectronic OLED materials
Pulsar timing and gravitational waves
Get PDFPulsars are magnetized rotating neutron stars that formed from the collapsed core of a massive star following a supernova. Charged particles are accelerated along the magnetic field lines producing electromagnetic radiation. As a result, the beam is confined along the magnetic poles. A misalignment between beam emission axis and rotation axis means that they are observed as a pulsating radio source like a lighthouse. The emitted signals from pulsars undergo delays due to their position, motion, relativistic effects and the effects of the interstellar medium. By analyzing and modelling the arrival times of pulses by account for every rotation of the pulsar, those physical parameters can be measured. This technique is called pulsar timing. Pulsar timing measurements provide various applications to fundamental physics and astronomy.
This thesis investigated 1) low frequency gravitational wave detection via multiple pulsar observations 2) the properties of a pulsar, PSR J1439−5501, through pulsar timing analysis and interstellar scintillation study 3) the potential usage of gravitational wave observations combined with pulsar timing measurements to study pulsar binaries.
Low-frequency gravitational waves are expected to be caused by cosmological phenomena such as super massive black hole binaries (SMBHBs) formed during galaxy mergers. By detecting such gravitational waves, the physics of the early Universe, which are often not possible to access via electromagnetic observations, can be measured. An array of pulsars, called pulsar timing array (PTA), can be used as a detector of such gravitational waves. I led a part of a PTA project to produce datasets of 25 precise pulsars used to search for nano-hertz gravitational waves. We obtained improved timing solutions of the pulsars with long timing baselines, from 14 to 25 years. I led analyses of the parallaxes and orbital period derivatives to measure distances and general relativistic effects in the orbital decays. Based on the produced data, we found the first evidence for a nHz gravitational wave background, potentially caused by SMBHBs from galaxy mergers.
PSR J1439−5501 is a binary system, consisting of a pulsar and a compact companion. Optical studies showed a potential detection of a relativistic effect causing a periodic signal delay in the binary. We detected the relativistic effect in the pulsar through pulsar timing analysis. By analyzing the +0.13 relativistic effect, we could measure the mass of pulsar (1.57 +0.30 −0.26 M⊙), companion (1.27 +0.13 −0.12 ⊙), and orbital inclination angle (75(1)°, or 105(1)°). An orbital period derivative, likely to be detected within a decade, will improve the overall measurements. Finally, we conducted a scintillation analysis, which uses the intensity variation in time and frequency, caused by the relative motion of the pulsar, the Earth and the ISM. By investigating the scintillation pattern in terms of the orbital motion of PSR J1439−5501 and annual variation, we estimated the position of the ascending node (16(7)° or −20(6)°), and the location of the screen (260 ± 100 pc).
When launched in 2030s, LISA, a space based gravitational wave observatory will enable us to detect gravitational waves at milli-hertz frequencies. Binary pulsars are one of the expected sources for LISA. Multi-messenger studies using gravitational wave and radio timing observations can be used to investigate physical properties of binary pulsars. We conducted simulations to show how two different observations can be combined to study binary pulsars. Based on the assumed properties of a hypothetical binary pulsar, we ran LISA and timing simulations. We showed that LISA can detect the signal of the assumed source in 3 months from the beginning of the observation. We considered priors from timing analysis for LISA, and showed that using priors can improve the measurements of distance and chirp mass. Finally, we reported that the individual masses of the binary pulsar can be better constrained if the inclination angle obtained from LISA is additionally considered
Dimensional Crossover in a Photonic Quantum Gas
No full textFor many-body quantum systems, dimensionality is known to exert a profound influence on the physical behaviour, allowing for the shaping of distinct phases of matter. In general, for lower dimensions, enhanced fluctuations serve to suppress long range order. For bosonic gases, for example, Bose-Einstein condensation in one dimension requires confinement that is stronger than linear in order to occur, in contrast to two-dimensional systems where harmonic confinement can suffice.
In this thesis, the dimensional crossover between one and two dimensions in a harmonically trapped photon gas has been experimentally investigated. The photons were confined within a dye filled optical microcavity, where polymer nanostructures produced by direct laser writing defined the trapping potential. By systematically adjusting the aspect ratio of the harmonic trap, the confinement was varied from an isotropic two dimensional regime to a highly anisotropic one dimensional regime.
The caloric properties of the photon gas were characterised across this transition, revealing that the sharp phase transition observed in two dimensions evolves into a smooth crossover in one dimension. This work enhances understanding of thermodynamic behaviour in photon Bose gases under confinement and demonstrates that here dimensionality can be used to tailor phase transition phenomena.
Furthermore, polymer cavities fabricated via direct laser writing afforded precise control over the confinement geometry, enabling exploration of variable potential landscapes. Proof of concept studies of advanced geometries, previously inaccessible, are presented, opening new directions for research in driven dissipative Bose gases and photonic quantum simulation platforms
Analysen zu intrazellulären Bakterien im Kontext des One-Health-Ansatzes
Get PDFIn dieser Dissertation wurden intrazelluläre bakterielle Erreger in Bezug auf deren Ausbreitung, antibiotische Therapie und Biologie untersucht. Der erste Teil der Arbeit befasste sich mit zoonotischen sowie neuartigen Erregern und konzentrierte sich auf epidemiologische Untersuchungen, darunter Analysen zu 199 Zecken aus Ghana. Diese parasitierten auf Fledermäusen und zeigten eine Durchseuchung mit Rickettsia (89%), Borrelia (34%) und Chlamydiales (12%). Es wurden neue Kandidaten der Gattung Rickettsia und eine neue Chlamydiales-Familie detektiert, welche zu den als sogenannten emerging pathogens beschriebenen Chlamydia-ähnlichen Bakterien zählt. Der Nachweis von Chlamydien in ghanaischen Zecken liefert weitere Indizien dafür, dass Zecken eine Rolle in deren Übertragung haben könnten. Der Fund von Borrelien zeigt, dass diese in Afrika entgegen dem bisherigen Wissen auch südlich des Breitengrades von 13° Nord zu finden sind. Die vorliegende Arbeit trug auch zu einer interdisziplinären Studie in Madagaskar bei, welche unter anderem das gesamte Spektrum zoonotischer Erreger, einschließlich intrazellulärer Bakterien, erfassen sollte. Hier wurden Parasiten von Ratten und Mäusen analysiert, wobei neben anderen Erregern Parachlamydia acanthamoebae, ein Chlamydia-ähnliches Bakterium, nachgewiesen wurde.
Vor dem Hintergrund dringend benötigter neuartiger Therapiestrategien befassten sich weitere Arbeiten mit Testungen zu neuen antibiotischen Substanzen. Zytotoxizitätsanalysen zeigten Unterschiede je nach verwendeten Zelllinien, Medien und Inkubationszeiten und verdeutlichten, dass verschiedene Versuchsaufbauten für eine umfassende Bewertung der Zytotoxizität hilfreich sind. Studien zum Lyseverhalten von Cyclodepsipeptiden gegenüber humanen Erythrozyten ergaben günstigere Eigenschaften von Hypeptin im Vergleich zu Teixobactin. Der Naturstoff CorA zeigte gute Aktivität gegen klinisch problematische persistierende Chlamydia trachomatis-Infektionen und entstehende sowie etablierte Staphylococcus aureus-Biofilme.
Abschließend sollte das Verständnis der ungewöhnlichen Biologie der Chlamydien vertieft werden. Mithilfe der Oberflächenplasmonenresonanzspektroskopie wurden erste Hinweise auf eine neuartige Glykogen-Bindefunktion von chlamydialen LysM-Proteinen gefunden, welche neue Bestandteile der Peptidoglykan-Ring-Biosynthesemaschinerie darstellen, die in Chlamydien als Penicillin-Zielstruktur dient
Standardized Evaluation of Chondrocyte Inflammation Model with TNF alpha
Get PDFThis study aimed to develop a standardized chondrocyte inflammation model by evaluating the effects of TNFα concentration and cell passage, and to further refine it into a dynamic model that more accurately reflects pathological inflammatory conditions. To establish a standardized chondrocyte inflammation model, bovine chondrocytes at different passages (P1-P3) were cultured as pellets and stimulated with TNFα at different concentrations (0.1 ng/mL to 100 ng/mL) for 48 h. To refine this into a dynamic model, passage 3 chondrocyte pellets were initially stimulated with 20 ng/mL TNFα for 48 h, followed by exposure to different concentrations of TNFα (0.2 ng/mL to 20 ng/mL) for the next 12 days. Gene expression (collagen 1, collagen 2, aggrecan, COMP, PRG4, MMP3, MMP13, IL-6, IL-8, NFkb1, COX2, PTGES2, Caspase-3) was determined. IL-6, MCP-1, nitric oxide and GAG released into the medium were measured. Histology staining was performed on pellets. The statistical significance was defined as p<0.05. This study showed that TNFα supplementation caused a decrease of anabolic gene expression in 48h pellet culture and this detrimental effect had a concentration threshold. Cell passage also affected the gene expression. Certain genes (COMP, collagen 1, MMP13, and Caspase-3) showed significant changes at lower concentrations of TNFα on day 4, but increasing the TNFα concentration did not elicit a stronger response. In contrast, other genes (MMP3, IL6, and COX2) exhibited different patterns. The responses of gene expression to the TNFα stimulation could be markedly different between day 4 and day 14. Protein analysis and histology results were in line with PCR results. Overall, TNFα exhibited a detrimental effect on chondrocytes. A clear threshold for the induction of inflammation was identified at 10 ng/mL. Following inflammation induction, TNFα at 0.2 ng/mL could maintain the inflammation process. Cell passage had an effect on model construction
Investigation of BRD9 inhibition as alternative treatment option for testicular germ cell tumors
Get PDFType II germ cell tumors are the most prevalent tumor in young men between the ages of 15 and 35 years. They arise from a block in primordial germ cell differentiation leading to a precursor lesion called germ cell neoplasia in situ (GCNIS). They are subgrouped into seminomas and non-seminomas. Non-seminomas comprise embryonal carcinomas which are able to differentiate into cells of all three germ layers as well as extraembryonic tissue classified as teratoma, yolk sac tumor and choriocarcinoma.
The standard treatment of testicular germ cell tumors (TGCT) is orchiectomy followed by cisplatin-based chemotherapy leading to high 5-year survival rates of 95 % but unfortunately 15-20 % of patients are still resistant to the treatment. Therefore, we found it very important to investigate alternative treatment options like epigenetic drugs. BET protein inhibitors interfering with the epigenetic landscape have already been shown to be effective in different cancer types like prostate cancer, glioblastoma and breast cancer. The bromodomain-containing protein-9 (BRD9) is part of a chromatin remodeling complex and an epigenetic reader which binds to acetylated lysine residues to activate gene expression by recruitment of other transcription factors. BRD9 shows significantly increased protein levels in cervical cancer and in malignant rhabdoid tumor (MRT) cells. For example, in acute myeloid leukemia (AML) cells the inhibition of BRD9 led to reduction of cell growth. Therefore, we found it very interesting to investigate the effect of the BRD9 inhibitor I-BRD9 in TGCTs.
First, we analyzed the expression of the target BRD9 in TGCT tissues and cell lines. Meta-analysis of microarray data in tissues as well as cell lines showed expression of BRD9. On protein level Western Blot also revealed comparable protein levels in TGCT cell lines while a tissue microarray (TMA) showed heterogenous expression of BRD9 in TGCT tissues. On the other hand, the lowest expression was found in the control cell line MPAF and in normal testis tissue indicating a promising starting point for testing the BRD9 inhibitor in TGCTs. XTT viability assays after I-BRD9 application led to reduced cell growth in all TGCT cells while the control cells were only slightly affected. FACS analysis revealed induction of apoptosis as well as G1-phase cell cycle arrest already after 24 hours of treatment with I-BRD9 in the TGCT cell lines while the control cells remained unaffected. RNAseq analysis displayed downregulation of a prominent network of pluripotency markers including NANOG, NODAL and KLF4 while genes involved in epithelium development were upregulated. These data suggest loss of the pluripotency state and differentiation towards an epithelial cell fate. Taken together, the BRD9 inhibitor I-BRD9 led to severe effects in TGCT cell lines like reduction of viability, induction of apoptosis and G1-phase cell cycle arrest while the control cells were only slightly affected. BRD9 inhibition induces loss of the pluripotency state and differentiation towards an epithelial cell fate. Most importantly, the data suggest I-BRD9 as a potential treatment alternative for TGCTs
Choriokapillaris-Flussausfälle bei Patienten mit Pseudoxanthoma elasticum
Get PDFZiel: Die Quantifizierung von sekundären Choriokapillaris-Flussausfällen bei Patienten mit Pseudoxanthoma elasticum (PXE) im präatrophen Frühstadium der Erkrankung, in Korrelation mit morphologischen Alterationen angrenzender Strukturen.
Methoden: In die prospektive Querschnittsstudie wurden 32 Augen von 21 Patienten mit PXE sowie 35 gesunde Augen von 35 Kontrollen eingeschlossen. Für beide Gruppen wurden jeweils spezifische Aufnahmen mittels optischer Kohärenztomographie-Angiographie (OCT-A; Makula 6x6mm) und optischer Kohärenztomographie (OCT; 30°x25°, 121 Scans) nach einem identischen Studienprotokoll angefertigt. Anschließend wurden Choriokapillaris Flussausfälle (Quantifizierung für jedes einzelne ETDRS-Feld) sowie die Dicken angrenzender Strukturen (äußere & innere Photorezeptorschicht, äußere Körnerschicht, Choroidea; Quantifizierung für jedes einzelne ETDRS-Feld) analysiert und miteinander korreliert.
Ergebnisse: Die Analyse des gemischt-multivariablen Modells für choriokapilläre Flussausfälle (CC-FA) zeigte signifikant erhöhte CC-FA bei Patienten mit PXE im Vergleich zur Kontrollgruppe (+13,6 [9,87–17,3], p<0,001), mit zunehmendem Alter (+0,22% pro Jahr; 95% KI 0,12–0,33; p<0,001) und je nach retinaler Lokalisation (signifikant höhere CC-FA in nasalen im Vergleich zu temporalen retinalen Arealen). Die Aderhautdicke (CT) unterschied sich nicht signifikant zwischen beiden Gruppen (p=0,078). CT und CC-FA korrelierten invers (-1,92µm pro %CC-FA; Interquartilsbereich -2,81 bis -1,03; p<0,001). Mit zunehmenden CC-FA zeigte sich außerdem eine signifikante Verdünnung der angrenzenden äußeren Netzhautschichten: der Photorezeptor-Außensegmente (-0,21µm/%CC-FA [p<0,001]), der Photorezeptor-Innensegmente (-0,12 µm/%CC-FA [p=0,001]) und der äußeren Körnerschicht (-0,72 µm/%CC-FA [p<0,001]).
Schlussfolgerungen: Bereits im im präatrophen Stadium ohne morphologische Verdünnung der Choroidea sind signifikante Veränderungen der Choriokapillaris-Perfusion bei Patienten mit PXE zu erkennen. Choriokapillaris-Flussausfälle spiegeln das PXE-typische zentrifugale Verteilungsmuster der kalzifizierten Bruch’schen Membran wider (signifikant höhere CC-FA in nasalen im Vergleich zu temporalen retinalen Arealen). Choriokapilläre Flussausfälle könnten daher als potentieller früher Parameter zum Krankheitsmonitoring sowie als Endpunkt für zukünftige klinische Interventionsstudien dienen
Data-driven Image Generation for Crop Growth Modeling
Get PDFCrop growth models play a crucial role in agriculture as they help to understand how crops grow and thrive. They allow farmers to predict how much harvest they can expect, which is important when planning, storing, and marketing food. They can optimize the use of water, fertilizers, and pesticides, which saves costs and contributes to sustainability by minimizing environmental impact. Moreover, they play a central role in research, for example, when investigating modern cultivation systems such as mixed crops and determining in which constellation different crops thrive. These aspects contribute to making agriculture more sustainable and efficient, which are both important and major challenges given climate change and a growing world population. There are many different crop growth models, which can be categorized into process-based models, data-driven models, and a mixture of both. This thesis focuses on data-driven models, which involve learning the growth behavior of plants from real data. Machine learning algorithms and methods are used for this purpose. In particular, we have two fundamental requirements for the crop growth models that are developed in this work. First, the model prediction should be based on an image showing the status quo of the plant at an early growth stage, in addition to other factors. Second, target parameters should not be determined directly, but an artificial image should be generated first that shows this plant's potential future growth stage. Implementing both requirements results in several advantages for the plant growth models. The model prediction is based on real data/observations in the field, allowing realistic images of future plants to be generated that are related to the input. The generated images can not only be reused as artificial sensor data but also provide significant added value in the visualization of the spatial crop distribution in the field and in model explainability.
For image generation we use the method of Generative Adversarial Networks (GANs) and perform experiments on the plants Arabidopsis thaliana, Brassica oleracea var. botrytis (cauliflower) and mixed crops consisting of Triticum aestivum (spring wheat) and Vicia faba (field bean). We first demonstrate that a data-driven crop growth model based purely on RGB images and a fixed growth step can generate realistic images for different field treatments. We show that the images not only look realistic but can also be used as artificial sensor data from which meaningful plant traits can be derived. Next, we increase the input flexibility of the data-driven model so that irregular sequences can be processed in the input and images of arbitrary growth stages can be generated. This enables not only interpolation and extrapolation of image sequences but also the generation of stochastic image distributions and pixel-wise visualization of growth variability. Finally, we present a third data-driven crop growth model that can handle a multi-modal input, i.e., an image plus additional growth influencing factors of different types. It is demonstrated that results from a process-based model can be utilized as input for a data-driven growth model, which provides the opportunity to add a spatial component to the process-based model or to re-calibrate it. Particularly noteworthy is the ability to recombine images and growth influencing factors, allowing for simulations that are analyzed qualitatively and quantitatively.
Overall, this work contributes significantly to data-driven crop growth modeling by generating realistic images of future growth stages from which realistic target parameters can be derived. In particular, the flexibility through irregular image sequences or multi-modal conditions in the input, the ability to generate a time-variable and stochastic output, and the integration with a process-based model are experimentally demonstrated. In combination with investigations on data requirements and experiments on the generalizability of crop growth models, the work provides essential indicators of how image-generating data-driven crop growth models can be used in agricultural practice in the future