Willkommen bei JLUpub
JLUpub ist das institutionelle Repositorium der Justus-Liebig-Universität.
JLUpub bietet Mitgliedern und Angehörigen der Universität die Möglichkeit neben wissenschaftlichen Dokumenten auch Forschungsdaten elektronisch zu veröffentlichen und dauerhaft zugänglich zu machen. Alle Veröffentlichungen erhalten einen Digital Object Identifier (DOI) und werden über nationale und internationale Bibliothekskataloge sowie Suchmaschinen nachgewiesen und auffindbar.
Neue Veröffentlichungen:
Item type: Item , Zahl der metastabilen Zustände bei einem Neuronalen Netzwerk mit Projektorkopplungen(1990) Kuhlmann, PeterDer Mittelwert der Zahl der metastabilen Zustände eines Neuronalen Netzwerkes mit Projektorkopplungen wird analytisch berechnet. Der Mittelwert wird dabei über zufällig verteilte Muster gebildet. Die Berechnung erfolgt mit Hilfe der Sattelpunktmethode.Item type: Item , Advances in Site-Selective Acylation of Pyranosides: From Oligopeptide Catalysis to Immobilized Catalysts in Flow(2025) Seitz, AlexanderIn the search for potential new applications for our group’s catalysts, we explored the idea of combining two catalytic motifs, that we have extensively studied before, in a multicatalytic reaction. The initial step involves performing a site-selective acetylation of partially protected pyranosides using a π-methyl-histidine (PMH)-containing oligopeptide catalyst. The resulting mono-alcohols could then be utilized in a selective, thiourea-catalyzed glycosylation reaction to generate 2-deoxy disaccharides. This thesis focuses on the first reaction of the proposed sequence. In the first part, we present the site-selective acylation of various methyl 4,6-O-protected pyranosides. We screened several tetrapeptide catalysts containing PMH and an adamantane moiety as the backbone. We identified catalysts capable of overcoming the intrinsic reactivity, which we determined using N-methylimidazole (NMI), for most of the pyranosides studied. To optimize the reaction conditions, we employed design of experiments (DOE) studies. We also investigated the impact of the 4,6-O-protecting group and the acylation reagent. Furthermore, we demonstrated that the selectivity of the reaction increased with the length of the applied peptide catalyst, suggesting that hydrogen-bonding interactions play a crucial role in selectivity. Finally, we showed that the observed reactivity could be maintained in more complex systems, as we successfully combined a benzylidene protection and the site-selective acetylation in a one-pot reaction. In the second part, we investigated the same pyranosides using peptide catalysts immobilized onto Wang-resin. We developed this approach to enhance the sustainability of our reaction, but also after initial studies concerning multicatalysis with thiourea and oligopeptide catalysts showed interference between the two, indicating that they must be separated locally. During the study, we demonstrated that we could easily synthesize the immobilized catalysts via solid-phase peptide synthesis (SPPS) and that they were still able to overcome the intrinsic reactivity of the substrates. We found that the catalysts could be reused for several reaction cycles with consistent results. Additionally, we showed that we could apply the catalyst in a continuous flow reaction without a significant loss in reactivity and selectivity. We used the long-term activity of the catalyst to convert large quantities of substrate and observed that the catalyst’s selectivity remained intact even after a temporary change in substrate.Item type: Item , Deciphering the role of EZH2 in the control of HIF2α signaling and its effects on cellular phenotypes in breast and lung cancer(2026) Kruijning, SalisaHypoxia is a hallmark of solid tumors and a critical driver of cancer progression, largely mediated by hypoxia-inducible factors (HIFs). While HIF1α has been extensively studied, the transcriptional regulation of HIF2α, encoded by the endothelial PAS domain protein 1 (EPAS1) gene, remains less well understood. Enhancer of zeste homolog 2 (EZH2), the catalytic subunit of polycomb repressive complex 2 (PRC2), is a known epigenetic regulator with canonical roles in gene repression via H3K27 tri-methylation and emerging non-canonical functions, including transcriptional activation. The interplay between EZH2 and HIF signaling, particularly regarding HIF2α, is largely unexplored. In this study, the role of EZH2 as a potential regulator of HIF2α in breast and lung cancer model systems was investigated. EZH2 knockdown decreased HIF2α protein under hypoxic conditions and EPAS1 mRNA levels under normoxic and hypoxic conditions in MDA-MB-231 and PC-9 cell lines. Restoration of EZH2 rescued EPAS1 expression. Mechanistic studies revealed that this regulation occurs independently of PRC2, EZH2’s methyltransferase activity, EZH1, Notch1 signaling, and transcriptional elongation. Chromatin immunoprecipitation demonstrated direct binding of EZH2 to a region approximately 1.7 kb downstream of the EPAS1 transcription start site, without enrichment of H3K27me3, supporting a non-canonical transcriptional activator function for EZH2. These findings indicate that EZH2 directly maintains EPAS1 transcription independent of chromatin repression and contributes to sustaining transcriptional activity within a globally repressive hypoxic environment. Functionally, EZH2 depletion impaired the expression of HIF2α target genes, including GLUT1 and PGK1, and reduced invasion capacity in MDA-MB-231 cells under hypoxia. In PC-9 cells, EZH2 knockdown decreased proliferation, which was partially rescued by transient HIF2α restoration, and anchorage-independent growth. These findings indicate that EZH2 promotes tumorigenicity at least in part through HIF2α. Clinical analyses revealed that high EZH2 and EPAS1 expression correlate with poor prognosis in breast cancer patients, underscoring the potential clinical relevance of this regulatory axis. Overall, this study establishes EZH2 as a novel non-canonical transcriptional activator of EPAS1, linking an epigenetic regulator to hypoxia signaling. These findings extend our understanding of EZH2 beyond its canonical repressive role and suggest that the EZH2-HIF2α regulatory axis may contribute to malignant phenotypes such as proliferation and invasion under hypoxic conditions. Future studies utilizing RNA-seq, in vivo models, and pharmacological inhibitors targeting EZH2 and HIF2α could provide further insight into the mechanistic and therapeutic potential of this regulatory pathway in cancer.Item type: Item , Lokales Wissen und kommunale Anpassung an den Klimwandel. Geographische und politologische Analysen für eine verbesserte Umsetzung(2026) Gierhake, KlausThe Context: This work exists as an update to the study: ‘Municipal adaptation to climate change in Quito (Ecuador) from the perspective of governmentality’ (http://dx.doi.org/10.22029/jlupub-5762). Here, two major content areas are analysed in more detail: 1) The local knowledge of a metropolitan area. 2) Social innovation as a process of combining different parts of existing local knowledge. This study focuses on institutions, their political and administrative actions, and areas with intersecting functions. Methodologically, this research is based on the field of applied geography. Therefore, a step-by-step refinement of this research approach is used. The Climate Convention: International conventions on global issues are highly complex. This applies to the Climate Convention as well. Here the focus is on discussions and resolutions relating to adaptation, the implementation of technical solutions in local communities. At COP27 in Egypt (2023), the following points were made exceptionally clear: (1) Progress in adaptation is very limited, varies greatly from region to region, and is highly fragmented. Adaptation measures could, in principle, have a number of additional positive effects. (2) There are a number of barriers, in particular the fact that the vast majority of international climate change funding has been concentrated on mitigation measures. Only a small proportion has been allocated to adaptation so far. This has been financed primarily from public funds. (3) Positive starting conditions can be identified, e.g. clear adaptation goals, responsibilities, and commitments to support. In particular, improved local knowledge of the risks, impacts and possible options is crucial. New forms of governance are possible. Local Knowledge: The discussion about local knowledge in large metropolitan areas is very recent. Metropolitan areas are the national centres of universities. They have a large civil society, and are often very diverse, bringing together immigrants from all parts of the country with their different cultures and forms of knowledge. This initial structure of great social diversity represents enormous potential. Local knowledge is then the sum of different segments of knowledge, from all groups and institutions, in very different sub-areas, and in one and the same space. Social innovations (‘Oslo Declaration’): This approach is complex in terms of content, combining ecological, social and economic objectives. However, the concept also addresses an even more comprehensive view: social innovations could also arise from combining different components of locally existing knowledge, focused on a new issue, e.g. adaptation to climate change. This necessitates a certain re-evaluation of general scientific discourse. Even scientific content, such as publications, that may appear ‘outdated’ at first glance, due to a sectoral perspective or simply because of the publication date, gains value in a new context. In this case, this can be demonstrated for the modernisation of a metropolis and adaptation to climate change. This requires implementation of qualitative research approaches, at least in the initial phase. Introduction of an innovation and territorial Diffusion: However, almost no examples from the Global South have been published on this topic. When this has occurred, it has been for projects with a very narrow understanding of ‘social’ (health, education) and a very limited project scope. On the other hand, there are examples of how local knowledge outside universities has been successfully structured and used to introduce social innovation. Such innovations can clearly also be introduced in the Global South. There is little empirical work available, although the example of Quito shows a completely new trend in geographical innovation research. Diffusion is possible even without widespread dissemination in the immediate local context. Existing institutional networks have enabled a ‘leap’ to the international level. Significant progress could be achieved by taking adequate account of local knowledge and its importance in social innovation approaches, including in international strategies. Some examples include: (1) The “UN Millennium Development Goals”, here in particular with reference to sustainable cities. (2) The German Research and Innovation Agenda ‘City of the Future’, especially with regard to the installation of social innovation in research and implementation. (3) The resolution of the ‘UN World Summit on Sustainable Development’ on a new perspective on ‘corporate social responsibility’ as an instrument for monitoring public policy. (4) Local adaptation to climate change as a starting point, and the results of the programme “100 Resilient Cities”. Outlook: The example of ‘Ecuador - Quito’ shows that considerable conceptual progress has been made. At the same time, the comprehensive level of ‘social innovation in Quito’ documents a remarkable global diffusion process of scientific results. This is highly significant in that this approach explicitly includes the ecological aspect of innovation in its concept and, in the specific case of Quito, also contains a remarkable document on sector planning. The local strategy for adapting to climate change deserves attention. The successful diffusion process of information therefore incorporates this technical aspect (climate change) without any additional effort. On this basis, regional governance strategies can be developed that offer a new quality of location factors. For example, a centre for identifying local (urban knowledge) and its possible combinations in different territorial contexts. Application-oriented/multidisciplinary and medium-term research remains necessary in order to overcome current knowledge deficits. Central research perspectives are identified: - Local knowledge, on the part of universities and the respective civil society. - The intellectual capital of local government, as an essential source of local knowledge can be used in a targeted manner. - The reasons for the emergence/existence of barriers are fundamentally complex. This necessarily includes the perspective of the effects of such barriers on a diffusion process. - A stronger territorial-institutional perspective is necessary in such research. The role of metropolitan areas should be examined more specifically in terms of their perspectives as centres of local knowledge and comprehensive social innovation, - In parallel with the completion of the current case study, it is necessary to undertake socio-political investigations into the role of individual actors, their values and attitudes towards social, ecological and economic changes.Item type: Item , Retrospektive Analyse und Vergleich zwischen interventionellem Ductus arteriosus Stenting und des chirurgischen aortopulmonalen Shunts als erste Palliation bei Patienten mit pulmonaler Atresie und ventrikulärem Septumdefekt(2025) Tsianakas, NikolaosBackground: Pulmonary atresia with ventricular septal defect (PA-VSD) is a complex congenital heart defect that requires staged palliation before definitive repair. Two primary palliative strategies—patent ductus arteriosus (PDA) stenting and aortopulmonary (AP) shunting—are commonly employed to maintain pulmonary blood flow. This study retrospectively compares outcomes between these two approaches. Methods: A retrospective analysis was conducted on 64 patients who underwent initial palliation with either PDA stenting (n=30) or AP shunting (n=34) between 1999 and 2019 at the Centre for Congenital Heart Disease (Kinderherzzentrum) Giessen. Outcomes were assessed across four stages: initial palliation (Stage 1), interstage period (Stage 2), complete surgical repair (Stage 3), and long-term follow-up (Stage 4). Primary endpoints included procedural success, complication rates, reintervention rates, and long-term survival. Results: Birth characteristics, including weight, length, and gestational age, were similar between groups. However, MAPCAs were more frequently observed in the AP shunt group (48.4% vs. 20%, p=0.020). At the time of initial palliation, the PDA stent group had significantly lower weight (p=0.029) and length (p=0.022). The hospital stay and ICU length were not significantly different between groups. Perioperative complications occurred in both groups but were slightly more frequent in the AP shunt cohort (53.3% vs. 43.3%, p=0.438). During the interstage period, complications were observed in 38.2% of the AP shunt group and 23.3% of the PDA stent group (p=0.199), though reintervention rates were comparable (p=0.683). Patients in the PDA stent group underwent complete repair significantly earlier (258.17 vs. 960.79 days, p=0.011). MAPCA unifocalization was more frequent in the AP shunt group (18.2% vs. 3.4%, p=0.109). The need for intraoperative LPA- or either RPA- or LPA-enlargement was higher in the PDA-Stent (65.5% vs. 29.4%, p=0.004 and 67.9 vs. 35.3, p= 0.011). Long-term follow-up showed no statistically significant difference in mortality, with one early postoperative death in the AP shunt group (p=0.352). The need for reintervention was slightly higher in the AP shunt group (81.8% vs. 62.1%, p=0.082), though not statistically significant. The type of reintervention differed, with PDA stent patients undergoing more catheter-based procedures and AP shunt patients requiring more surgical reinterventions. Conclusions: Both PDA stenting and AP shunting are viable palliative options for PA-VSD, with similar long-term survival outcomes. However, PDA stenting appears to facilitate earlier complete repair with fewer interstage complications. AP shunting remains a reliable approach, particularly in patients with MAPCAs. And seems to reduce the burden of PA stenosis requiring enlargement intraoperatively. Future studies with larger cohorts and longer follow-up as well as randomized clinical trials are necessary to refine treatment algorithms further.