Ludwig-Maximilians-Universität München
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Treppenbaukunst um 1600
No full textDie Arbeit behandelt die Treppenbaukunst um 1600 am Beispiel der Residenzen in Salzburg und München. Eingehend wird die Salzburger Residenz betrachtet, die unter Fürsterzbischof Wolf Dietrich von Raitenau einen bedeutenden architektonischen Wandel hin zu einer frühbarocken Schlossanlage erfuhr. Ein zentrales Element der Studie ist die 3D-Rekonstruktion der Prunktreppe der Salzburger Residenz. Die digitale Modellierung ermöglicht eine präzise Analyse des ursprünglichen, nicht mehr erhaltenen Entwurfs sowie eine klare Differenzierung einer zweiten Bauphase unter mutmaßlichem Einfluss Vincenzo Scamozzis. Die Rekonstruktion verdeutlicht, wie neue architektonische Konzepte im Bauprozess zu einer veränderten Gestaltung und Funktion der Treppe führten. Die Treppenbaukunst wird nicht nur als funktionales Element, sondern als wichtiger Bestandteil der höfischen Repräsentation hervorgehoben. Gleichzeitig werden neue Einsichten in den kulturellen Austausch zwischen Italien und den nordalpinen Fürstentümern jener Zeit gewonnen
Monoallelic TYROBP deletion is a novel risk factor for Alzheimer’s disease
Get PDFBiallelic loss-of-function variants in TYROBP and TREM2 cause autosomal recessive presenile dementia with bone cysts known as Nasu-Hakola disease (NHD, alternatively polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy, PLOSL). Some other TREM2 variants contribute to the risk of Alzheimer’s disease (AD) and frontotemporal dementia, while deleterious TYROBP variants are globally extremely rare and their role in neurodegenerative diseases remains unclear. The population history of Finns has favored the enrichment of deleterious founder mutations, including a 5.2 kb deletion encompassing exons 1–4 of TYROBP and causing NHD in homozygous carriers. We used here a proxy marker to identify monoallelic TYROBP deletion carriers in the Finnish biobank study FinnGen combining genome and health registry data of 520,210 Finns. We show that monoallelic TYROBP deletion associates with an increased risk and earlier onset age of AD and dementia when compared to noncarriers. In addition, we present the first reported case of a monoallelic TYROBP deletion carrier with NHD-type bone cysts. Mechanistically, monoallelic TYROBP deletion leads to decreased levels of DAP12 protein (encoded by TYROBP) in myeloid cells. Using transcriptomic and proteomic analyses of human monocyte-derived microglia-like cells, we show that upon lipopolysaccharide stimulation monoallelic TYROBP deletion leads to the upregulation of the inflammatory response and downregulation of the unfolded protein response when compared to cells with two functional copies of TYROBP. Collectively, our findings indicate TYROBP deletion as a novel risk factor for AD and suggest specific pathways for therapeutic targeting
Human Footprint and Forest Disturbance Reduce Space Use of Brown Bears (Ursus arctos) Across Europe
Get PDFThree-quarters of the planet's land surface has been altered by humans, with consequences for animal ecology, movements and related ecosystem functioning. Species often occupy wide geographical ranges with contrasting human disturbance and environmental conditions, yet, limited data availability across species' ranges has constrained our understanding of how human pressure and resource availability jointly shape intraspecific variation of animal space use. Leveraging a unique dataset of 758 annual GPS movement trajectories from 375 brown bears (Ursus arctos) across the species' range in Europe, we investigated the effects of human pressure (i.e., human footprint index), resource availability and predictability, forest cover and disturbance, and area-based conservation measures on brown bear space use. We quantified space use at different spatiotemporal scales during the growing season (May–September): home range size; representing general space requirements, 10-day long-distance displacement distances, and routine 1-day displacement distances. We found large intraspecific variation in brown bear space use across all scales, which was profoundly affected by human footprint index, vegetation productivity, and recent forest disturbances creating opportunity for resource pulses. Bears occupied smaller home ranges and moved less in more anthropized landscapes and in areas with higher resource availability and predictability. Forest disturbances reduced space use while contiguous forest cover promoted longer daily movements. The amount of strictly protected and roadless areas within bear home ranges was too small to affect space use. Anthropized landscapes may hinder the expansion of small and isolated populations, such as the Apennine and Pyrenean, and obstruct population connectivity, for example between the Dinaric Pindos population and the Alpine or Carpathian population. Our findings call for actions to maintain bear movements across landscapes with high human footprint, for example by maintaining forest integrity, to support viable bear populations and their ecosystem functions
DNA Mimic Foldamer Recognition of a Chromosomal Protein
Get PDFHelical aromatic oligoamide foldamers bearing anionic side chains that mimic the overall shape and charge surface distribution of DNA were synthesized. Their interactions with chromosomal protein Sac7d, a non-sequence-selective DNA-binder that kinks DNA, were investigated by Surface Plasmon Resonance (SPR), Isothermal Titration Calorimetry (ITC), Circular Dichroism spectroscopy (CD), melting curve analysis, Atomic Force Microscopy (AFM), and Nuclear Magnetic Resonance (NMR), as well as by single crystal X-ray crystallography. The foldamers were shown to bind to Sac7d better than a DNA duplex of comparable length. The interaction is diastereoselective and takes place at the DNA binding site. Crystallography revealed that the DNA mimic foldamers have a binding mode of their own and that they can bind to Sac7d without being kinked
Evaluation of a context-aware chatbot using retrieval-augmented generation for answering clinical questions on medication-related osteonecrosis of the jaw
Get PDFThe potential of large language models (LLMs) in medical applications is significant, and Retrieval-augmented generation (RAG) can address the weaknesses of these models in terms of data transparency and scientific accuracy by incorporating current scientific knowledge into responses. In this study, RAG and GPT-4 by OpenAI were applied to develop GuideGPT, a context aware chatbot integrated with a knowledge database from 449 scientific publications designed to provide answers on the prevention, diagnosis, and treatment of medication-related osteonecrosis of the jaw (MRONJ). A comparison was made with a generic LLM (“PureGPT”) across 30 MRONJ-related questions. Ten international experts in MRONJ evaluated the responses based on content, language, scientific explanation, and agreement using 5-point Likert scales. Statistical analysis using the Mann–Whitney U test showed significantly better ratings for GuideGPT than PureGPT regarding content (p = 0.006), scientific explanation (p = 0.032), and agreement (p = 0.008), though not for language (p = 0.407). Thus, this study demonstrates RAG to be a promising tool to improve response quality and reliability of LLMs by incorporating domain-specific knowledge. This approach addresses the limitations of generic chatbots and can provide traceable and up-to-date responses essential for clinical practice
Assessment of CNNs, transformers, and hybrid architectures in dental image segmentation
No full textObjectives
Convolutional Neural Networks (CNNs) have long dominated image analysis in dentistry, reaching remarkable results in a range of different tasks. However, Transformer-based architectures, originally proposed for Natural Language Processing, are also promising for dental image analysis. The present study aimed to compare CNNs with Transformers for different image analysis tasks in dentistry.
Methods
Two CNNs (U-Net, DeepLabV3+), two Hybrids (SwinUNETR, UNETR) and two Transformer-based architectures (TransDeepLab, SwinUnet) were compared on three dental segmentation tasks on different image modalities. Datasets consisted of (1) 1881 panoramic radiographs used for tooth segmentation, (2) 1625 bitewings used for tooth structure segmentation, and (3) 2689 bitewings for caries lesions segmentation. All models were trained and evaluated using 5-fold cross-validation.
Results
CNNs were found to be significantly superior over Hybrids and Transformer-based architectures for all three tasks. (1) Tooth segmentation showed mean±SD F1-Score of 0.89±0.009 for CNNs, 0.86±0.015 for Hybrids and 0.83±0.22 for Transformer-based architectures. (2) In tooth structure segmentation CNNs also outperformed with 0.85±0.008 compared to Hybrids 0.84±0.005 and Transformers 0.83±0.011. (3) Even more pronounced results were found for caries lesions segmentation; 0.49±0.031 for CNNs, 0.39±0.072 for Hybrids and 0.32±0.039 for Transformer-based architectures.
Conclusion
CNNs significantly outperformed Transformer-based architectures and their Hybrids on three segmentation tasks (teeth, tooth structures, caries lesions) on varying dental data modalities (panoramic and bitewing radiographs).
Clinical significance
As deep-learning-based image analysis is part of modern dentistry, practitioners and dental researchers should be aware of strength and limitations of modern model architectures for dental-image analysis. Models that demonstrate optimal performance in other domains do not necessarily constitute the optimal selection for the purpose of dental imaging
Prognostic impact of combined loss of RB1, p53 and p21 in muscle-invasive bladder cancer
Get PDFIntroduction
Muscle-invasive bladder cancer (MIBC) represents a genetically heterogeneous disease with limited prognostic markers. This study aimed to validate the prognostic relevance of combined alterations in cell cycle regulators RB1, p53, and p21 in a broad cohort of MIBC patients undergoing radical cystectomy (RC).
Material and Methods
We analyzed formalin-fixed paraffin-embedded material from MIBC patients who underwent RC at the Department of Urology, University Hospital, Ludwig-Maximilians-University Munich. Tissue microarrays (TMAs) from 251 MIBC patients (pT2-pT4) were constructed, incorporating triplicate cores from tumor center and front. Immunohistochemical expression of RB1, p53, and p21 was assessed using a four-grade scoring system. Prognostic associations with overall survival (OS) and cancer-specific survival (CSS) were evaluated using multivariable Cox regression, Kaplan-Meier curves, and log-rank tests.
Results
We assessed 4518 stainings from 251 patients. Single marker analysis revealed no significant association between the loss of RB1, p53, or p21 and OS or CSS. However, the loss of two or three markers was significantly associated with worse OS (HR 3.49, 95 % CI 1.28–9.50; p = 0.01) and CSS (HR 11.2, 95 % CI 1.46–86.04; p = 0.02).
Conclusions
RB1, p53, and p21 are insufficient as single prognostic markers in MIBC but demonstrate significant prognostic relevance when analyzed in combination. These findings underscore the need for multi-marker approaches in prognostic modeling and personalized treatment strategies for MIBC
Empirische Studien in studentischen Abschlussarbeiten im Studienfach DaF/Z: Exemplarische Analyse typischer Fehler und (hochschul-)didaktische Empfehlungen
No full textDer Artikel schließt an Forschungsarbeiten von Ines Busch-Lauer im Bereich des wissenschaftlichen Schreibens an und untersucht spezifische Herausforderungen für internationale Studierende. Im Fokus stehen Abschlussarbeiten, die von den Autorinnen am Herder-Institut der Universität Leipzig sowie der Friedrich-Schiller-Universität Jena betreut wurden, in denen Studierende eine eigene empirische Studie durchgeführt haben. Die Autorinnen weisen nicht nur auf Möglichkeiten studienbegleitender Seminarangebote hin, sondern zeigen an konkreten Beispielen, auf welche Stolpersteine in der Betreuung des Schreibprozesses geachtet werden sollte. Abschließend wird für die curriculare Verankerung von Seminaren plädiert, die speziell auf das Schreiben akademischer Texte abzielen, um die wissenschaftlichen Kompetenzen der Studierenden nachhaltig zu stärken
