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Retrospektive matched-pair Analyse zum Vergleich einer sequenziellen Konditionierung vor HLA-kompatibler vs. haploidentischer Stammzelltransplantation bei Patienten mit Akuter Myeloischer Leukämie und hohem Risiko
Towards a cell-biological understanding of the formation and dissociation of neurotoxic protein aggregates
Einfluss der Schichtdicke auf die Transluzenz und die Biegefestigkeit von zahnmedizinischen Restaurationsmaterialien
Das Faktum der Wirklichkeit
Ohne Fiktion keine Rede von Gott. Denn allein die Fiktion ermöglicht es dem Menschen über etwas zu reden, über das man eigentlich nicht reden kann. Aus dieser notwendigen Fiktionalität folgt allerdings nicht, dass „Gott“ oder Religion mit Illusionen, nützlichen Unwahrheiten oder gar Märchen gleichzusetzen sind. Bei genauer Betrachtung erscheinen solch religionskritische Verkürzungen des Phänomens der Fiktion schnell als unangemessen. Vielmehr zeigt sich die Fiktion als das evolvierte Werkzeug menschlicher Wirklichkeitsbewältigung, das in Kunst, Gesellschaft und Wissenschaft eine tragende Rolle spielt. Entgegen der landläufi gen Annahme können Fiktionen wahre Aussagen über die Welt treffen. Mehr noch, indem sie das Unsagbare sagbar machen, ermöglichen Fiktionen dem Menschen den Zugang zu einer tieferen Sinndimension der Wirklichkeit. Fiktionen avancieren so zum Ermöglichungsgrund jeder Religion.
Um zu einem solchen Verständnis des Fiktionsbegriffs zu gelangen, sind Streifzüge durch die Evolutionspsychologie und Wissenschaftstheorie sowie die Erzähl- und Kulturtheorie vonnöten. Am Ende steht ein Fiktionsbegriff, der innertheologische Gräben überwinden und apologetisch die Rede von Gott plausibilisieren kann.
Maximilian Schalück studierte evangelische Theologie, Germanistik und Erziehungswissenschaften an der LMU München und der Universität Helsinki. Er schloss seine Promotion 2023 in der evangelischen Theologie als Stipendiat der Evangelisch-Lutherischen Kirche in Bayern und der Konrad-Adenauer-Stiftung und 2024 sein Referendariat für das Lehramt am Gymnasium in Bayern ab. Seine Interessensgebiete liegen in der Religionsphilosophie, der Theologie des 20. Jahrhunderts und der interdisziplinären Forschung.Without fiction, there is no religion. Even more, without fiction the essential human tool for coping with reality would be missing as fiction plays a key role in art, society and science. In contrast to popular belief, fiction is able to formulate truthful statements about the world and enables a deeper understanding of reality.
The present study shows how an interdisciplinary approach to the phenomenon of fiction helps to overcome friction within theology and to apologetically validate the discourse on god. It draws on evolutionary psychology, cultural theory and theory of science as well as ontology and current theology.
Maximilian Schalück studied Protestant Theology, German Studies, and Educational Sciences at LMU Munich and the University of Helsinki. He completed his doctorate in 2023 in Protestant Theology as a scholarship holder of the ELKB and the KAS. In 2024 he finished his teacher training for secondary education I and II in Bavaria. His areas of interest include the philosophy of religion, 20th-century theology, and interdisciplinary research
The refined consensus model of pedagogical content knowledge as a basis for evaluating and increasing pre-service biology teachers’ competence in the field of academic and science language
Every member of the society needs scientific literacy to be able to follow and participate in the current social discourse. Biology lessons aim to develop students’ scientific literacy, and students’ outcomes depend on their biology teachers’ professional competence, especially their pedagogical content knowledge (PCK). Within this dissertation, teachers’ PCK will be described on the basis of the Refined Consensus Model of PCK (RCM) which integrates sev-eral models of teachers’ competence. It differentiates between three realms of PCK: collec-tive PCK (cPCK), personal PCK (pPCK) and enacted PCK (ePCK), which occurs in action while a teacher plans (ePCKP), teaches (ePCKT) and reflects (ePCKR) a lesson. These three components of ePCK are described as the Plan-Teach-Reflect Cycle of ePCK. For the trans-formation processes between the realms of PCK, two filters are assumed: teachers’ profes-sional values and motivational orientations, thus affective components of teachers’ compe-tence, as a filter moderating the transformation between cPCK and pPCK; and teachers’ noticing and knowledge-based reasoning as a filter moderating the transformation between pPCK and ePCK. The effect of teachers’ PCK on their students’ outcomes is mediated by biology-specific lesson quality features such as cognitive activation or elaborate model use. Since it is impossible to learn any biological content without the required academic and biol-ogy-specific science language, biology teachers need PCK in the field of academic and biolo-gy-specific science language: this forms the basis they need to consider appropriate language use and scaffolding in order to realise biology-specific lesson quality features in biology in-struction.
This dissertation aimed to (1) evaluate the RCM with regard to its proposed filters be-tween the three realms of PCK and to the Plan-Teach-Reflect Cycle of ePCK, (2) include the language in biology instruction into existing models of teachers’ competence, and (3) devel-op materials to assess biology lesson plans and biology instruction on the basis of the re-search findings.
To achieve those aims, three studies were conducted within the framework of a BMBF-funded nationwide initiative to improve teacher education in Germany (Qualitätsof-fensive Lehrerbildung). All studies took place in obligatory seminars for pre-service teachers and followed a pre-/post-test design; different aspects of participants’ professional compe-tences were tested. Results showed that knowledge-based reasoning moderates the trans-formation between pPCK and ePCK and therefore, can be defined as a filter within the RCM. Motivational orientations, professional values and noticing were hypothesised as fil-ters, too, but research findings did not support this assumption. Training the Plan-Teach-Reflect Cycle of ePCK as a whole or in parts enhances pre-service biology teachers’ pPCK, motivational orientations and ePCK. Including the Teach-component to the cycle strength-ens the effect in contrast to replacing the Teach-component by presentations of lesson plans. The same effects were hypothesised for professional values as well, but research findings did not support this assumption.
Therefore, pre-service teachers’ knowledge-based reasoning could be identified as one filter between pPCK and ePCK. It is possible to assess and to foster some aspects of pre-service teachers’ professional competence in the field of academic and science language, and to include the language in biology instruction into existing models of teachers’ competence in order to enable the realisation of biology-specific lesson quality features. Deriving from the research findings, there are implications for future research as well as for science teacher education: it is recommended to detect further filters between the realms of PCK, and strat-egies to map and increase science teachers’ professional values, and to investigate the impact of science teachers’ PCK in the field of academic and science language on their students’ outcomes. Since the research within this dissertation provides high ecological validity, the findings are recommended to be implemented into science teacher education programmes: to include an additional focus on language in science instruction, to train pre-service teach-ers’ knowledge-based reasoning together with their PCK, and to include the Teach-component
Connecting core-collapse supernova remnants and their central neutron stars
The topic of this thesis is the investigation of core-collapse supernova remnants and their central neutron stars, with an emphasis on the intrinsic connection between the two. This is achieved via spectroscopic and astrometric analysis of their X-ray emission, which is characteristic for the hot plasma and energetic nonthermal processes occurring in these objects.
On one hand, this work investigates the velocity distribution of central compact objects (CCOs), a class of neutron stars characterized by purely thermal emission. Via careful astrometric calibration of data from the Chandra X-ray telescope, it is shown that none of the investigated CCOs exhibits a problematically high velocity in the celestial plane, which would exceed the expectation for the recoil experienced by the neutron star during the explosion.
Furthermore, the presented proper motion measurements are used, in combination with the expansion of the associated supernova remnants (SNRs), to constrain their ages in a model-independent manner. This allows dating the SNR Puppis A to an age of 4600 +/- 700 years, and establishing strict upper limits on the ages of the SNRs G350.1-0.3 and RX J1713.7-3946, at 700 and 1700 years, respectively.
This is complimented by spectroscopic analysis of the X-ray emission of the SNRs Puppis A and Vela with physically motivated models, using data from the recently launched SRG/eROSITA telescope.
In Puppis A, this allows for the identification of regions which were only recently shock-heated, as well as a detailed search for ejecta produced during the explosion. This reveals that Puppis A contains an atypically high fraction of silicon for a core-collapse SNR, as well as a misalignment of intermediate-mass elements with the recoil direction implied by the motion of the neutron star.
Similarly, in the much older Vela SNR, an unexpected composition of X-ray detected ejecta is revealed, with strongly supersolar abundance ratios of neon and magnesium compared to oxygen. Furthermore, the presented analysis for the first time allows for isolating the hard synchrotron emission of the central Vela pulsar wind nebula from the softer thermal emission from the SNR. This effort demonstrates a much larger extent of the synchrotron nebula than visible at other wavelengths, at a radius up to three degrees. A possible explanation for its phenomenology is the slow diffusion of high-energy electrons through a relatively weak ambient magnetic field, similarly to the gamma-ray halos observed around several older pulsars
Cationic carrier supported peptide-based nanosystems for tumor targeting
The delivery of therapeutic materials, including small molecules, genes, and oligonucleotides, offers great opportunities for the treatment of many diseases like genetic disorders, neurodegenerative diseases, and various cancer types. Especially sequence-defined polycationic oligoaminoamids (OAAs), as a polymeric nanoplatform, are interesting candidates to deliver nucleic acids and other structures with a polyanionic surface like red CDs. OAAs not just enhance the nanoparticle properties of the formulation but also bring the benefit of enabling the integration of targeting domains and other surface modifications. This thesis displays the research of fine-tuned OAAs, optimized for their different cargos (pDNA, siRNA, CDs), modified targeting peptides, attached via a monodisperse polyethylene glycol (PEG) spacer via click chemistry for enabling direct targeting of several tumor cell lines.
In the first part a highly advanced cationizable lipo-oligoaminoamide (lipo-OAA), 1214, was used to compact siRNA. The created polyplex then was postmodified with a retro-enantio peptide (reTfR) for TfR targeting. Improved gene silencing is demonstrated in TfR-expressing KB and DU145 cells. Analogous pDNA polyplexes are successfully used for receptor-mediated gene delivery in TfR-rich K562 cells and Neuro2a cells. Six lipo-OAAs differing in their lipidic domain and redox-sensitive attachment of lipid residues were tested to evaluate the impact of core polyplex stability on receptor-dependent gene transfer. The current study could show, that well stabilizing 1214 / reTfR-2 polyplexes were far better suitable for siRNA delivery than for pDNA delivery. The less stabilized NonOcA-OAA 1258 or 1285 / reTfR-2 was suitable for pDNA delivery into erythroleukemic K562 cells, and the ssbb-based bioreducible DecA- or NonOcA-OAAs 1284 or 1285 / reTfR-2 best suited for neuroblastoma cells. Concluding, the retro-enantio peptide reTfR presented clear TfR receptor targeting, displaying an interesting candidate for improved in vivo application, due to its additional stability against serum proteases.
In the second part a 4-armed OAA library of 21 carrier structures to coat and entrap red CDs (rCDs) was synthesized and screened to evaluate the best performer 1696, which encapsulated rCDs in a superior way, displayed by particle size, distribution, and zeta. As a next step this perfectionated formulation was postmodified with several peptide ligands to test its efficacy on U87 cells. rCD-1696-L57 conjugates had a superior transfection efficacy compared to non-targeted rCD-1696 conjugates, addressing the targeting efficacy of the L57 peptide to the LRP1 receptor, creating a CD-based model for potential BBB targeting, with the far sight of finding therapeutic agents able to treat CNS related neurogenerative diseases or brain cancer like glioma
Immune cell profiles of tumor and regional lymph nodes in surgically treated non-small cell lung cancer
In recent years, improved understanding of the interaction between cancer and the immune system has led to the introduction of various immunotherapy approaches, all harnessing the power of the immune system to impede tumor development, growth and spread. The immune system is a vastly complex network and response to a foreign antigen must be launched in a coordinated fashion both locally as well as systemically. In the case of NSCLC, this requires a response in the lung tissue surrounding the tumor as well as the regional lymph nodes. Most previous studies that attempted to characterize this response were limited by investigating only tumor or lymph nodes, and those who investigated both did not include tumor-free lymph nodes.
To tackle these caveats, I have composed a diverse cohort of surgically-treated NSCLC patients containing both long- and short-term survivors. I investigated morphological features in tumor and matched tumor-bearing and non-tumor bearing lymph nodes and analyzed their association with survival. I then used these results to inform transcriptomic analyses of these tissues to determine how morphological changes were reflected on a molecular level.
In this thesis, I showed that tumor-infiltrating lymphocytes and macrophages are key components of the immune response in the primary tumor and non-tumor bearing lymph nodes. The importance of lymphocytes in immune mediated tumor control is further corroborated by an association between CD4 expression in non-tumor bearing lymph nodes and survival.
Based on these results, immune transcriptomics showed a negative impact of immune dysfunction measured by Tumor Immune Dysfunction and Exclusion (TIDE) score on patient survival. When comparing patients with high levels to patients with low levels of immune dysfunction, CD8 expression was significantly higher in patients with lower levels of immune dysfunction. A more in depth analysis explored the relation of the expression of multiple immune cell exhaustion markers and survival. Among these, TIM-3 and PD-L1 were identified as the only markers to be associated with survival in more than one tissue.
Overall, this work presented an integrative approach to assessing immune composition and dysfunction. Levels of immune cell exhaustion markers may indicate a dysfunctional immune status and can predict survival after curative surgery in NSCLC. This work provides the basis for further investigation of the clinical relevance of immune cell exhaustion in early-stage NSCLC