Ludwig-Maximilians-Universität München

Digitale Hochschulschriften der LMU
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    22455 research outputs found

    A novel class of mRNA lipid nanoparticles (LNPs) optimized by the chemical evolution approach

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    Impact of high-latitude atmosphere-ionosphere coupling on the space weather

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    Characterisation of nuclear actin family proteins and SNF2 ATPase chromatin remodellers during endodyogeny by Toxoplasma gondii

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    Experimental analysis of fulgurite formation

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    Study of accreting neutron stars, massive black holes and cosmological forecasts for SRG/eROSITA

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    This thesis is dedicated to a broad range of problems related to accretion. Two types of objects are studied: active galactic nuclei (AGN) - accreting massive black holes at the centres of galaxies, and X-ray pulsars - accreting neutron stars with extremely high magnetic fields. In the first part of this thesis, we investigate massive black holes (BH) dwelling at the centres of almost all massive galaxies. The mass of BHs correlates with the bulge mass of their host galaxies, making these objects an important asset for galaxy evolution. Some BHs emit copious amounts of radiation due to the accretion of matter — they are called active galactic nuclei (AGN). Sky surveys in X-ray wavelengths are effective at discovering AGNs and studying their evolution. The spatial distribution of AGNs serves as an effective tracer of the Large-Scale structure (LSS) of the Universe. We focus on the all-sky X-ray survey performed by the SRG/eROSITA telescope, which has already discovered close to three million AGNs. We assess the prospects of cosmological measurements with eROSITA based on the LSS of AGNs and galaxy clusters. We find that the marginalised errors on cosmological parameters (energy density of dark and baryon matter, Hubble constant) achieve precision 1-10%. The predicted precision of cosmological constraints expected from the SRG/eROSITA all-sky survey is competitive with the constraints from current and planned cosmological surveys and missions. We present a method for identifying eROSITA X-ray sources in sky surveys in optical bands. This task is paramount for estimating redshifts of X-ray sources. We combine machine learning techniques with a Bayesian approach to match the sources from the X-ray catalogue of eROSITA in the Lockman hole with optical sources. The accuracy achieves 94% for the entire X-ray catalogue. We perform the search for active nuclei of dwarf (low-mass) galaxies using eROSITA data. Dwarf galaxies are expected to host central black holes of lower mass compared to the bulk of AGNs. These BHs are thought to be the relics of the first black holes and are important to constrain the black hole seeding scenarios. We construct a catalogue of 82 dwarf galaxies with nuclear X-ray activity - an unambiguous indicator of a massive accreting BH. We calculate the fraction of the dwarf galaxy population hosting an active black hole as a function of X-ray luminosity and galaxy stellar mass. The fraction of active dwarfs is as large as 2% for low X-ray luminosity and drops for higher luminosities. We serendipitously discover a tidal disruption of a star by a central BH in a dwarf galaxy and demonstrate the ability of tidal flares to uncover the population of dormant black holes. In the second part of this work, we focus on the study of X-ray pulsars- accreting neutron stars (NS) in stellar binary systems. The material is captured by the magnetic field and directed to a NS, where ample X-ray emission is produced. The geometry of accretion flows is complex and depends on a number of parameters, such as magnetic field strength. We use a novel technique to study the geometry of systems with X-ray emission of a NS reprocessed by surrounding matter. We analyse two pulsars, V0332+53 and Swift J0243.6+6124. The latter is an extremely luminous object (ultra-luminous X-ray source). We study pulsations of the reprocessed emission in both pulsars. We show that in J0243 the reprocessed emission is weakly variable over the pulsar rotational phase and direct emission shows larger pulsations. We conjecture that the pulsar is located at the centre of a well, formed by a geometrically thick accretion disc truncated by the magnetic field. The inner sides of the well are illuminated by the pulsar and produce reflected emission. We estimate the magnetic field value of a pulsar by measuring the Doppler broadening of the iron line. In V0332 the iron K-edge absorption depth and K-alpha line intensity pulsate. Flux as a function of the rotational phase shows two dips of identical shape separated by 180 degree. The absorption edge is the strongest during the dips, but its depth cannot be caused by the absorption of X-rays by the infalling material. We conclude that the data can not be explained with simple models of emission reprocession by surrounding matter, emphasising the importance of further studies of such objects for pinpointing the geometry of accretion flows

    Adultes und künstliches Myokardgewebe als neuartige in-vitro Modelle in der Herzforschung

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    New approaches to improve treatment planning in radiotherapy with photons, protons and carbon ions

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    Validierung eines klinisch anwendbaren Biomarkers zur Vorhersage des Therapieansprechens bei Patienten mit akuter myeloischer Leukämie

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    Die akute myeloische Leukämie (AML) stellt eine klinisch und biologisch heterogene Erkrankung dar. Die Entscheidung für oder gegen eine intensive Induktionschemotherapie bei Diagnosestellung ist in vielen Risikogruppen deutlich erschwert. Prädiktive Biomarker ermöglichen die Identifikation von Patienten, die mit hoher Wahrscheinlichkeit nicht von einer Induktionschemotherapie profitieren. Das Ziel dieser Arbeit war es, das prädiktive, auf Genexpression basierende Modell des PS29MRC (Predictive Score 29 Medical Research Council) nach Herold et al. (2018) auf die praxistaugliche NanoString-Plattform zu übertragen und in einem unabhängigen, multizentrischen, retrospektiv analysierten Patientenkollektiv zu validieren. Initial wurden 384 unbehandelte Proben aus dem Register der AMLCG (Acute Myeloid Leukemia Cooperative Group) in die Studie eingeschlossen. Nach der Präparation, Hybridisierung und Purifikation der Proben erfolgte die Quantifizierung der Genexpression mit Hilfe des automatisierten NanoString-Analyzers. Für weitere Analysen wurden schließlich nur Proben mit adäquater Qualität, zytogenetischer MRC-Risikostratifizierung (Medical Research Council) und erfolgter Evaluation des Ergebnisses der Induktionschemotherapie einbezogen (n = 351). Den primären Endpunkt stellte ein Versagen der Induktionschemotherapie gemäß den Empfehlungen des European LeukemiaNet 2017 dar. Das Modell des PS29MRC wurde in univariaten sowie multivariaten Analysen als signifikanter prädiktiver Biomarker für ein Versagen der Induktionschemotherapie bestätigt. Das kontinuierliche Modell des PS29MRC war bisherigen prädiktiven Scores wie denen nach Walter et al. (2015) oder nach Ng et al. (2016) in der Vorhersage eines Therapieversagens deutlich überlegen. Durch die Anpassung des Cut-Off-Wertes an die NanoString-Plattform konnte das dichotome Modell des PS29MRC Patienten mit niedrigem (n = 234) und hohem (n = 117) Risiko identifizieren, das jeweils mit der Wahrscheinlichkeit eines Therapieversagens sowie mit einem reduzierten Gesamtüberleben assoziiert war. Im behandlungsbezogenen Gespräch mit Patienten eingesetzt könnte das Modell der individuellen Risikovorhersage zudem die Kommunikation erleichtern und zu einer informierten Therapieentscheidung beitragen. Zur Optimierung des Modells nach Herold et al. (2018) sind weitere prospektive Untersuchungen mit größeren Fallzahlen unter Berücksichtigung neuer Behandlungsregime notwendig. Das Ziel sollte dabei sein, Hochrisikopatienten zu identifizieren, individuelle Therapiekonzepte zu formulieren und somit das Langzeitüberleben von Patienten mit AML zu verbessern

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    Digitale Hochschulschriften der LMU
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