68034 research outputs found
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Living on the Edge: ROS Homeostasis in Cancer Cells and Its Potential as a Therapeutic Target
No full textReactive oxygen species (ROS) act as double-edged swords in cancer biology—facilitating tumor growth, survival, and metastasis at moderate levels while inducing oxidative damage and cell death when exceeding cellular buffering capacity. To survive under chronic oxidative stress, cancer cells rely on robust antioxidant systems such as the glutathione (GSH) and thioredoxin (Trx), and superoxide dismutases (SODs). These systems maintain redox homeostasis and sustain ROS-sensitive signaling pathways including MAPK/ERK, PI3K/Akt/mTOR, NF-κB, STAT3, and HIF-1α. Targeting the antioxidant defense mechanisms of cancer cells has emerged as a promising therapeutic strategy. Inhibiting the glutathione system induces ferroptosis, a non-apoptotic form of cell death driven by lipid peroxidation, with compounds like withaferin A and altretamine showing strong preclinical activity. Disruption of the Trx system by agents such as PX-12 and dimethyl fumarate (DMF) impairs redox-sensitive survival signaling. Trx reductase inhibition by auranofin or mitomycin C further destabilizes redox balance, promoting mitochondrial dysfunction and apoptosis. SOD1 inhibitors, including ATN-224 and disulfiram, selectively enhance oxidative stress in tumor cells and are currently being tested in clinical trials. Mounting preclinical and clinical evidence supports redox modulation as a cancer-selective vulnerability. Pharmacologically tipping the redox balance beyond the threshold of cellular tolerance offers a rational and potentially powerful approach to eliminate malignant cells while sparing healthy tissue, highlighting novel strategies for targeted cancer therapy at the interface of redox biology and oncology
Meta-metamodel-Independent Model Transformations
No full textModel-driven engineering efficiently manages complexity through high-level abstractions and model transformations, progressively refining models into executable code. However, current approaches require models to adhere to the same meta-metamodel, limiting their applicability to isolated ecosystems like Eclipse/Ecore or UML. The adoption of Building Information Modeling (BIM) has highlighted the need for transforming models across various life cycle phases. Yet, the fractured modeling landscape of BIM poses challenges as of existing solutions’ restriction on complying to the same meta-metamodel and supported modeling formalisms (e.g., Eclipse/Ecore or UML). We introduce a novel meta-metamodel-independent model transformation formalism, accompanied by a domain-specific modeling language for declaring transformation rules at the meta-model level. Our approach leverages a formalism-independent core language for on-the-fly establishment of meta-models, enabling meta-metamodel-independent model transformations. We validate our proposal through case studies in construction and software engineering, demonstrating its feasibility and generalizability
An Ecosystem of DSMLs for Building Commissioning
No full textBuilding Information Modeling (BIM) has advanced the construction industry from simple 2D/3D CAD to semantically rich, object-oriented, and visually intuitive modeling. However, unlike, e.g., the UML or SysML, BIM’s modeling formalisms lack universal applicability and full life cycle coverage, confining its use largely to architectural design. Key trades like building control remain insufficiently integrated, leading to inefficiencies and misaligned design and operational requirements. This paper presents an ecosystem of domain-specific modeling languages (DSML) integrated with BIM, to expand its capabilities to additional trades such as building control. By embedding operational requirements (cf. the building control system installation) during the design phase by integrating them into the BIM model, the subsequent application of model-driven deployment ensures alignment with operational objectives. Validation in a Living Lab at the University of Innsbruck highlights the approach’s benefits, including faster commissioning and improved energy efficiency, representing a step toward comprehensive, BIM-based building design and operation
Characteristics and outcomes of patients hospitalized for infection with Influenza A, SARS-CoV-2 or respiratory syncytial virus in the season 2023/2024 in a large German primary care centre
Full text linkData from a large population of patients (adults and children) admitted to a primary care hospital due to SARS-CoV-2, Influenza A or RSV infection showed, that in the season 2023/24 the relative contributions of these infections had remained similar to those of 2022/23. About 53% of patients had SARS-CoV-2, 23% Influenza A and 22% RSV, with a very low proportion of coinfections. Clinical outcomes were similar for SARS-CoV-2 and Influenza, while RSV showed higher relative rates of ICU admission and death, and these were even elevated compared to 2022/23. These findings underline that especially in adults, RSV infection poses a significant clinical risk compared to other common respiratory infections including SARS-CoV-2, despite much lower prevalence. Whether this should have implications regarding vaccination remains to be clarified
Harp: Data Harmonization for Computational Tissue Deconvolution across Diverse Transcriptomics Platforms
Full text linkMotivation
The cellular composition of a solid tissue can be assessed either through the physical dissociation of the tissue followed by single-cell analysis techniques or by computational deconvolution of bulk gene expression profiles. However, both approaches are prone to significant biases. Tissue dissociation often results in disproportionate cell loss, while deconvolution is hindered by biological and technological inconsistencies between the datasets it relies on.
Results
Using calibration datasets that include both experimentally measured and deconvolution-based cell compositions, we present a new method, Harp, which reconciles these approaches to produce more reliable deconvolution results in applications where only gene expression data is available. Both on simulated and real data, harmonizing cell reference profiles proved advantageous over competing state-of-the-art deconvolution tools, overcoming technological and biological batch effects
Development of a Liposome-Based Serological Assay for SARS-CoV-2 Variants with Special Emphasis on Coupling Chemistries Required to Maintain Protein Antigenicity
No full textThe conjugation of proteins to the outer membranes of liposomes is a standard procedure used in bioanalytical and drug delivery approaches. Herein, we describe the development of a liposome-based surrogate assay for the quantification of SARS-CoV-2 neutralizing antibodies. Taking into consideration differences in amino acid sequences within the receptor-binding domain (RBD) of SARS-CoV-2 Spike proteins derived from five selected variants of concern (VoC), we studied the impact of coupling chemistries on physicochemical properties and antigenicity. Naturally occurring lysine residues were used for standard EDC/NHS chemistry, while an N-terminal Cys-tag and a C-terminal Avi-tag were genetically added to the proteins for site-directed immobilization. Despite only minor differences regarding the number, positioning, and sequence context of lysine residues within the different RBD variants, those differences led to a dramatic change in their functionality after EDC/NHS coupling. In contrast, site-specific biotinylation of the proteins alongside targeted immobilization on streptavidin- or neutravidin-modified liposomes resulted in restored functionality and enhanced storage stability across all variants. The developed adaptable liposome-based test showed excellent correlation with an established pseudovirus neutralization test and could identify variations in neutralization patterns of Alpha/Delta and Omicron variants in patient sera. The study highlights the benefits of using neutravidin-liposomes for site-directed protein immobilization with independence from the proteins’ amino acid sequences, enhanced storage stability, and applicability to various biotinylation strategies, serving as a versatile platform technology that can also be applied to the coupling of other proteins or peptides used for diagnostic purposes
Gewerbliche Immobilienfinanzierungen im Zeitalter der Unsicherheit – die Ergebnisse des German Debt Projects 2025
No full textopenCost & EZB: APC-Förderbedingungen mit EZB-Zeitschriftendaten verknüpfen und einrichtungsspezifisch anzeigen
No full textDie Elektronische Zeitschriftenbibliothek (EZB) ermöglicht es ihren Anwenderbibliotheken, Informationen zur Förderung von Publikationskosten bereitzustellen. Dies umfasst bisher einen globalen Informationstext, Kontaktinformationen und Verweise auf weitere Informationsangebote der Einrichtung. Im Rahmen des DFG-Projektes openCost wird dieses Angebot in Abstimmung mit der EZB-Community ausgebaut, um eine passgenaue Erfassung und Bereitstellung der APC-Förderbedingungen in der eigenen Einrichtung zu ermöglichen.
Neben der Bereitstellung von Förderinformationen können in der EZB Zeitschriften vordefinierten Kategorien zugeordnet werden, die für das Publizieren relevant sind, wie „Diamond OA Journal“ oder „Subscribe to Open“. Die Zuordnung zu den Kategorien erfolgt durch die EZB-Community und automatisiert anhand valider Quellen wie dem DOAJ. Nun werden die Kategorien technisch so erweitert, dass sie mit spezifischen Förderbedingungen verknüpft werden können. Wenn eine Zeitschrift der Kategorie „Indexed in DOAJ“ zugeordnet ist, kann eine Einrichtung die Förderbedingungen hinterlegen, die speziell für Zeitschriften dieser Kategorie gelten. Anstelle des globalen Informationstextes wird dann in der Benutzeroberfläche die spezifische Förderinformation der Einrichtung für diese Kategorie angezeigt. Analog können auch Förderbedingungen für Transformationsverträge, wie den DEAL-Verträgen, hinterlegt und mit den enthaltenen Zeitschriften verknüpft werden.
In einem weiteren Schritt soll die Abbildung von Mitgliedschaften in der EZB ermöglicht werden. Erste prototypische Umsetzungen zeigen bereits die Förderbedingungen an der Universität Regensburg, verknüpft mit den entsprechenden Zeitschriften. Im Anschluss sollen mit der EZB-Community Konzepte zur Dateneingabe und -pflege entwickelt werden.
Mit diesen Erweiterungen, insbesondere in Bezug auf Kostentransparenz, wird die Publikationskostenförderung in den jeweiligen Einrichtungen spezifischer und übersichtlicher gestaltet
Programmable phonon-assisted resonant energy transfer between moiré cells in charge-tunable MoSe2-WS2 heterobilayers
No full textMoiré superlattices in van-der-Waals heterostructures offer a versatile platform for exploring emergent quantum phenomena. In type-I MoSe2-WS2 moiré superlattices, the large lattice mismatch ensures robustness of the moiré period against twist-angle disorder. The excitonic ground state is formed by moiré-trapped MoSe2 intralayer excitons. However, a key challenge is the controlled transfer of excitonic energy across moiré sites. This work investigates gate-controlled phonon-assisted resonant energy transfer (RET) as a means to transfer excitonic energy between moiré cells. By harnessing the interplay between resonantly excited moiré excitonic complexes and single or few phonons, energy transfer pathways can be modulated via the charging state of moiré cells. We discuss two potential RET mechanisms: phonon-assisted resonant tunneling and Förster-like dipole–dipole transfer. Our findings highlight the potential of this approach for excitonic circuits and nanoscale energy transport, paving the way for future applications in quantum technologies
Highly efficient lateral spin valve device based on graphene/hBN/Fe3GeTe2
No full textIn this work we report efficient out-of-plane spin injection and detection in an all-van der Waals based heterostructure using only exfoliated 2D materials. We demonstrate spin injection by measuring spin-valve and Hanle signals in non-local transport in a stack of Fe3GeTe2 (FGT), hexagonal boron nitride (hBN) and graphene layers. FGT flakes form the spin aligning electrodes necessary to inject and detect spins in the graphene channel. The hBN tunnel barrier provides a high-quality interface between the ferromagnetic electrodes and graphene, eliminating the conductivity mismatch problem, thus ensuring efficient spin injection and detection with spin injection efficiencies of up to P = 40%. Our results demonstrate that FGT/hBN/graphene heterostructures form a promising platform for realizing 2D van der Waals spintronic devices