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Die Konstruktion von Nichtreligion im Onlineforum r/atheism. Eine religionswissenschaftliche Studie.
No full textEin großer und weiter wachsender Anteil der Weltbevölkerung ist religionslos. Trotz quantitativer Größe und qualitativer Vielfalt sind nichtreligiöse Gruppen von der Forschung bislang allerdings erst unzureichend in den Blick genommen worden. Gerade die Religionswissenschaft übersieht zumindest in struktureller Hinsicht das halbe Feld und den halben Diskurs, wenn sie nur die positiv religionsbezogenen Phänomene betrachtet. Die vorliegende Dissertation verortet sich in der religionswissenschaftlichen Nichtreligionsforschung und widmet sich der größten atheistischen online community der Welt, dem Onlineforum r/atheism im sozialen Medium Reddit.
Das Forschungsdesign orientiert sich dabei am Charakter der dortigen Akteure als selbstreferentiellen und weltanschaulichen Atheistinnen und Atheisten. Entsprechend fragt die Studie schwerpunktmäßig nach den Identitätskonstruktionen in diesem Forum (kollektive Identität, Selbst- und Feinbilder, Othering) sowie nach der dort konstruierten atheistischen Weltanschauung (v. a. in Hinblick auf die Verständnisse von Religion, Nichtreligion und Wissenschaft, sowie auf die Menschen- und Geschichtsbilder). Dies geschieht methodisch mit einer mehrstufigen Qualitativen Inhaltsanalyse. In theoretischer Hinsicht kombiniert die Arbeit den relationalen Ansatz der Nichtreligionsforschung mit einem diskursiven Religionsbegriff.
Im Ergebnis konnte erstmals im Detail gezeigt werden, wie online eine imagined atheist community gestiftet wird. Dies geschieht v. a. durch den Charakter des Forums als einer Selbsthilfegruppe sowie durch eine ausgeprägte Dichotomisierung zwischen der atheistischen In-Group und der imaginierten religiösen Out-Group. Darüber hinaus kann festgehalten werden, dass das Forum r/atheism durch einen ausgeprägten Religionsbezug geprägt und Teil des globalen Religionsdiskurses ist. Die Akteure stellen dabei eine charakteristische Fraktion innerhalb des weltweiten Aushandlungsprozesses um Religion dar. Dabei lässt sich das Forum als eine postchristliche Gemeinschaft erkennen, die sich u. a. durch ein aus dem Protestantismus stammendes „fundamentalistisches“ Religionsverständnis auszeichnet. Durch dieses und weitere inhaltliche Merkmale steht die Forumsgemeinschaft in ihrem Mainstream dem sog. Neuen Atheismus nahe, und unterscheidet sich von anderen gegenwärtigen Atheismen
E6AP Inhibition and Metformin Treatment: Two Novel Strategies to Block the Growth of HPV-Positive Cancer Cells?
No full textOncogenic types of human papillomaviruses (HPVs) are major human carcinogens. The therapy of HPV-associated malignancies, such as cervical cancer, remains challenging and novel treatment options are urgently needed. This thesis aimed to gain a deeper understanding of the molecular mechanisms that sustain the proliferation of HPV-positive cancer cells and to identify new strategies to block their growth, thereby paving the way towards novel therapeutic approaches.
My studies uncovered that the cellular ubiquitin ligase E6-associated protein (E6AP), an interaction partner of the HPV E6 oncoprotein, is essential for maintaining the proliferation of HPV-positive cancer cells by exerting a previously unrecognized anti-senescent function. RNA interference (RNAi)-mediated E6AP silencing, unlike E6 silencing, led to a potent induction of cellular senescence, an irreversible growth arrest. Notably, the pro-senescent effect of E6AP downregulation was specifically observed in HPV-positive cancer cells. Proliferation studies and cell cycle analyses revealed that the cellular growth inhibition and senescence induction upon E6AP repression critically depend on the activation of the p53-p21 axis as well as on the pocket proteins retinoblastoma protein (pRb) and p130. Additionally, my results showed that Metformin, which is being discussed for repurposing in cancer therapy, can also inhibit the proliferation of HPV-positive cancer cells. However, this effect is reversible and, further, was found to be independent of Metformin’s potential to downregulate the expression of the HPV E6 and E7 oncogenes. Moreover, my experiments demonstrated that Metformin exhibits complex functional interactions with chemotherapeutic agents in both HPV-positive and HPV-negative cancer cells. Whereas Metformin can protect against senescence induced by the prosenescent drug Etoposide, it can enhance the pro-apoptotic effects of Cisplatin, particularly after pre-treatment with Metformin. My mechanistic studies further revealed functional key roles for p53 and a truncated form of the BH3-interacting domain death agonist (BID) protein, t-BID, in mediating the cooperative effects between Metformin and Cisplatin.
Collectively, my findings identify E6AP as a critical anti-senescent factor in HPV-positive cancer cells that is essential for their proliferation. E6AP might therefore serve as a new therapeutic target, with specificity for HPV-positive cancer cells. Moreover, my results uncover complex effects of Metformin on the phenotype of HPV-positive and HPV-negative cancer cells. Importantly, Metformin can substantially increase the anti-proliferative effects of Cisplatin, a drug that plays a key role in the treatment of HPV-positive cancers. This indicates that combinatorial treatments with Metformin and Cisplatin could potentially be of therapeutic benefit
Characterising emission line nebulae in nearby galaxies
No full textThe ionized interstellar medium (ISM) is a central part of the galactic ecosystem, where the interaction between stars and gas becomes exceptionally vivid. Its main constituents – HII regions, planetary nebulae (PNe), and supernova remnants – trace different phases of stellar evolution and provide complementary perspectives on feedback and galactic structure. The emergence of integral field spectroscopy has opened new insights and enabled studies of the various components in unprecedented detail. We use a combination of observations – including MUSE spectroscopy and high-resolution HST imaging – across a diverse sample of nearby star-forming galaxies to study various aspects of emission line nebulae. In the first part of this thesis, we construct a dedicated PNe catalogue and measure the distance to each galaxy with the planetary nebula luminosity function (PNLF). The results highlight the potential of this method, but also its challenges, such as misclassified PNe or internal extinction. The second part links HII regions to the young stellar populations that power them. We identify potential age tracers – such as the equivalent width EW(Hα), the flux ratio Hα/FUV, and the ionization parameter log q – that all show a correlation with stellar age. Building on this catalogue, we compare the predicted ionizing photon flux from the stars to the observed flux from the HII region to compute the escape fraction of ionizing photons. Individual regions yield comparatively high escape fractions, though with large variations and significant uncertainties. When combining all nebulae and stars on a galactic scale, the value remains high, but it becomes more robust and consistent across the galaxy sample. It makes it clear that stellar feedback is not locally bound, but influences the galaxies as a whole
MITTENDRIN MUT MACHEN: Endbericht zur Wissenschaftlichen Begleitforschung der MITTENDRINNENSTADT in Heidelberg 2022-2025
No full textDer Endbericht der wissenschaftlichen Begleitforschung zur MITTENDRINNENSTADT legt die zentralen Erkenntnisse aus der dreijährigen Heidelberger Umsetzung des Bundesförderprogramms „Zukunftsfähige Innenstädte und Zentren“ (ZIZ) dar. Auf Basis eines Methoden-Mix aus leitfadengestützten Interviews, einer Dokumenten- und Kommunikationsanalyse sowie einer umfangreichen Passant*innen- und Onlinebefragung untersuchte die Begleitforschung, wie sich die durch das Förderprogramm umgesetzten Maßnahmen, Prozesse und Akteurskonstellationen auf die Heidelberger Innenstadtentwicklung auswirkten. Die Ergebnisse zeigen eine aktive und beteiligungsbereite Heidelberger Stadtgesellschaft, die ihren Stadtraum aufmerksam wahrnimmt und Veränderungsprozesse kritisch wie konstruktiv begleitet. Sichtbare städtebauliche Verbesserungen, darunter die Sanierung des Bismarckplatzes, die Aufwertung des Iqbal-Ufers und das Projekt Bella Park, tragen maßgeblich zu einer positiven Wahrnehmung der Innenstadt bei. Gleichzeitig hat sich mit dem Team Heidelberg, dem Innenstadtbüro und dem Verfügungsfonds eine neue kooperative Governance-Struktur etabliert, die innovative Gestaltungsspielräume eröffnet. Dennoch bleiben kurze Projektzeiträume, administrative Hürden und eine begrenzte Einbindung neuer Akteur*innen zentrale Herausforderungen für eine langfristig tragfähige Innenstadtentwicklung
Functional spatial genomics uncover a fusion-regulated and clinically relevant driver of metastasis in Ewing sarcoma
No full textMetastasis is the major negative prognostic factor across cancer entities, yet how driver oncogenes shape transcriptional programs facilitating metastatic spread is poorly understood. In Ewing sarcoma (EwS), a highly aggressive pediatric soft-tissue and bone sarcoma, driven by chimeric FET::ETS transcription factors, low activity of the fusion oncoproteins are thought to promote metastasis, yet, the underlying mechanisms and key downstream effectors still remain largely elusive. Therefore, a spatial functional genomics approach in the EwS model identified for the first time that FET::ETS-low activity signature is localized at the invasive front of patient’s tumor and is associated with the transcriptional induction of the multifunctional shuttle LIM domain only protein 7 (LMO7). Integrating these data with clinical information showed that high LMO7 expression levels are associated with worse prognosis and the development of metastatic disease. Gene network analyses of transcriptomic data from patient-derived tumors as well as functional proteogenomic analyses of EwS cell lines with/without conditional RNA-interference-mediated knockdown of LMO7, highlight this gene as a regulatory hub involved in multiple pro-metastatic processes including epithelial-to-mesenchymal transition and cytoskeleton remodeling. Functional experiments prove that LMO7 silencing decreases the capacity of EwS cells for clonogenic growth and migration in vitro, which is mirrored by reduced primary tumor growth and complete absence of metastatic burden in vivo.
In sum, these results identify LMO7 as clinically relevant key downstream regulator of FET::ETS fusions in EwS and provide an example of how the integration of functional, spatial and clinical data can shed light on how oncogenes promote metastasis in cancer
Progress on antiproton cooling and an improved direct limit on the antiproton lifetime
No full textThe Baryon Antibaryon Symmetry Experiment (BASE) probes CPT symmetry by comparing the fundamental properties of protons and antiprotons with highest precision. We have compared proton/antiproton charge-to-mass ratios with a fractional precision of 16 parts in a trillion and proton and antiproton magnetic moments with a precision on the parts per billion level. Located at CERN’s Antimatter Factory, BASE is currently constrained to perform the high-precision studies within the accelerator shutdown period. For this purpose, several antiprotons are caught and then stored almost indefinitely in a dedicated Reservoir trap.
High precision g-factor measurements require regular re-cooling of an isolated antiproton. This thesis describes the characterization and optimization of a novel cyclotron-mode
cooling device, which lowers the cyclotron mode cooling time from previously 15 hours to only 8 minutes and thus enables us to maximize the number of measurement cycles in the limited window of opportunity. With the improved cooling performance, the spin transition detection error rate is reduced by more than three orders of magnitude to < 0.000023.
Furthermore, the optimization and routine operation of the Reservoir trap enabled us to store antiprotons for (up until now) 1.5 years, with a typical consumption rate of about one particle per two months for experimental purposes, highlighting the feasibility of long-term measurement campaigns and experiments with extremely rare species. By continuously monitoring the stored antiprotons in this time range, this thesis extracts a direct lower limit on the antiproton lifetime of 52.54 years with a confidence level of 68%. This improves the previous best value by a factor of five
Ermittlung von NS-Raubgut in Bibliotheksbeständen: Provenienzforschung an der Universitätsbibliothek Heidelberg
No full textWährend der NS-Zeit wurden Millionen Bücher aus privaten Sammlungen und öffentlichen Bibliotheken von staatlichen Stellen beschlagnahmt. Viele dieser Werke, sofern sie nicht zerstört wurden, gelangten entweder direkt oder über Umwege in die Bestände wissenschaftlicher Bibliotheken. Seit 2023 untersucht die Universitätsbibliothek Heidelberg in dem von der Stiftung Deutsches Zentrum Kulturgutverluste geförderten Projekt „Ermittlung von NS-Raubgut in den Zugängen der Jahre 1933 bis 1950 der Universitätsbibliothek Heidelberg” den Verbleib von NS-Raubgut in ihren Beständen. Im Gespräch mit Südwest-Info erläutert Projektmitarbeiter Dr. Christian Gildhoff die historischen Hintergründe, die methodischen Herausforderungen und die Perspektiven der Provenienzforschung an wissenschaftlichen Bibliotheken
Underconfidence and the low-experimentation trap
No full textWe study how confidence bias affects investment in learning via experimentation, a mechanism critical for technology adoption under uncertainty. We hypothesize that bias direction and strength predict how willingness to experiment diverges from unbiased agents. We measure revealed and stated demand for experimenting with drought-resistant crop varieties of 1,957 farmers in West Africa, a climate change hotspot. Consistent with our hypothesis, confidence bias strongly predicts willingness to experiment. The effect, however, is driven exclusively by underconfident agents, among whom females are overrepresented. In deteriorating environments, this behavioral friction undercuts effective technology diffusion and risks trapping individuals in maladapted production environments
Epigenetic Deregulation by BCOR Oncogenic Fusions in Sarcomas
No full textSarcomas are a heterogeneous group of mesenchymal tumours arising in bone and soft tissue with a higher incidence in children and young adults. Owing to sarcomas’ molecular diversity and lack of available experimental models, progress in treatment has stagnated in the past 5 decades. Many sarcomas arise due to translocations that fuse transcriptional and epigenetic regulators, resulting in characteristic transcriptional landscapes. A commonly affected target is BCL6 co-repressor (BCOR), a member of the non-canonical Polycomb repressive complex 1.1 (ncPRC1.1) which promotes gene silencing by ubiquitinating lysine 119 of histone H2A (H2AK119ub). ncPRC1.1 is crucial in development and differentiation. In sarcomas, BCOR fuses to recurrent partners, leading to remarkably overlapping transcription and DNA methylation patterns, indicative of a convergent pathological mechanism. However, this mechanism is still not understood, and we do not know how these mutations affect the role of BCOR within ncPRC1.1.
I modelled two oncofusions, BCOR::CCNB3 and ZC3H7B::BCOR, in immortalized human mesenchymal stem cells by simultaneous induction of the fusions and silencing of the endogenous BCOR gene. RNA sequencing (RNA-seq) revealed drastic transcriptional remodeling which mimicked a patient-derived BCOR sarcoma transcriptional signature, and upregulation of many PRC targets. Canonically, assembly of ncPRC1.1 is initiated by binding of BCOR and PCGF1 to the targeting subunit KDM2B. Despite drastically remodelling the transcriptional landscape, I found that the BCOR oncofusions are retained at KDM2B-marked ncPRC1.1 sites genome-wide. Using co-immunoprecipitation (co-IP) and an imaging-based in vitro chromatin recruitment assay, I showed that the BCOR fusions interact with PCGF1 and KDM2B and participate in active ncPRC1.1 complexes that deposit H2AK119ub, ruling out a loss-of-function mechanism. To investigate how, then, these oncofusions were contributing to the sarcoma transcriptional signature, I analyzed their interactomes by co-IP coupled to mass spectrometry (co-IP-MS). Thus, I identified novel interactors gained by the BCOR fusions, including many transcriptional activators and cofactors. Shared between the two fusions were the histone acetyltransferases EP300/CREBBP, which were previously identified as fusion partners to BCOR in other cancers. EP300/CREBBP recruitment to the BCOR fusions was mediated by the fusion partners CCNB3 and ZC3H7B. To confirm their role in transcriptional regulation in sarcomas, I developed a sarcoma patient-derived cell line with a BCOR::CCNB3 alteration (BC3). In the BC3 cells, EP300 and H3K27ac co-occupied BCOR::CCNB3 genome loci. EP300 inhibition and CRISPR/Cas9 knock out of BCOR::CCNB3 both led to downregulation of PRC target gene sets. Despite the transcriptional effect, EP300 inhibition in the BC3 cells did not lead to a proliferative defect.
This work demonstrated that BCOR::CCNB3 and ZC3H7B::BCOR recruit transcriptional activators that lead to transcriptional rewiring by a gain-of-function mechanism. EP300/CREBBP, which were identified amongst the top interactors, were found to contribute to the characteristic transcriptional profiles. Together, this work reveals key mechanistic insights into the role of fusion proteins in sarcomas. These findings lay the groundwork for future studies to elucidate how these altered transcriptional programs contribute to carcinogenesis in patients and provide mechanistic rationale for novel therapeutic targets
