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Influenza A Virus Production Following Quality by Design Principles
No full textABSTRACT Establishing manufacturing processes for cell culture‐based pharmaceutical products involves managing multiple parameters that can affect yield and efficiency, as well as process robustness and product quality. Implementing Quality by Design (QbD) principles can support process optimization, while streamlining the chemistry, manufacturing, and control aspects for regulatory approval. In this study, we mimic a QbD approach based on an influenza A virus production process using two clonal suspension Madin‐Darby canine kidney (MDCK) cell lines with distinct characteristics. We performed a quantitative risk assessment including biological and technical parameters to identify the Critical Process Parameters (CPPs). To comprehensively study the effects and interactions of four CPPs, we used an Ambr 15 scale‐down system following a Design of Experiments (DoE) approach. After data analysis and modeling, we obtained design spaces characterized by high robustness with a less than 1% risk of failure and even some indications for virus titer and yield improvement, while keeping process‐related impurities such as DNA and total protein concentration low. These findings were subsequently verified at a more than 100‐fold higher working volume. Taken together, our approach may stimulate ideas for the implementation of streamlined process development and regulatory approval in the field of viral vaccine production
Subtyping Burkitt Lymphoma by DNA Methylation
No full textABSTRACT Burkitt lymphoma (BL) is an aggressive germinal center B‐cell‐derived malignancy. Historically, sporadic, endemic, and immunodeficiency‐associated variants were distinguished, which differ in the frequency of Epstein–Barr virus (EBV) positivity. Aiming to identify subgroups based on DNA methylation patterns, we here profiled 96 BL cases, 17 BL cell lines, and six EBV‐transformed lymphoblastoid cell lines using Illumina BeadChip arrays. DNA methylation analyses clustered the cases into four subgroups: two containing mostly EBV‐positive cases (BL‐mC1, BL‐mC2) and two containing mostly EBV‐negative cases (BL‐mC3, BL‐mC4). The subgroups BL‐mC1/2, enriched for EBV‐positive cases, showed increased DNA methylation, epigenetic age, and, in part, proliferation history compared to BL‐mC3/4. CpGs hypermethylated in EBV‐positive BLs were enriched for polycomb repressive complex 2 marks, while the CpGs hypomethylated in EBV‐negative BLs were linked to, for example, B‐cell receptor signaling. EBV‐associated hypermethylation affected regulatory regions of genes frequently mutated in BL (e.g., CCND3 , TP53 ) and impacted superenhancers. This finding suggests that hypermethylation may compensate for the lower mutational burden of pathogenic drivers in EBV‐positive BLs. Though minor, significant differences were also observed between EBV‐positive endemic and sporadic cases (e.g., at the SOX11 and RUNX1 loci). Our findings suggest that EBV status, rather than epidemiological variants, drives the DNA methylation‐based subgrouping of BL.Intramural Research Program https://doi.org/10.13039/10003069
Suppression of hydrolytic enzyme activities by short-term aeration of periodically anoxic soils: Evidence from upland ecosystems
No full texthttp://dx.doi.org/10.13039/100021828 DAAD Regional Office New Yorkhttp://dx.doi.org/10.13039/501100004543 China Scholarship Councilhttp://dx.doi.org/10.13039/501100001655 Deutscher Akademischer Austauschdiens
A theoretical rethinking of ecosystem services from the perspective of social-ecological system
No full texthttp://dx.doi.org/10.13039/501100001809 National Natural Science Foundation of Chin
Reservoir characterization by push–pull tests employing kinetic interface sensitive tracers – Quantification of residual trapping in geological storage of carbon dioxide
No full texthttp://dx.doi.org/10.13039/501100002347 Federal Ministry of Education and Research Bonn Officehttp://dx.doi.org/10.13039/501100001659 German Research Foundatio
The relevance of social-milieus for forest policy research – insights from a Germany-focused review
No full textThe Future of GEOROC: Database Curation for the Geochemical Community
No full textThe GEOROC database (Geochemistry of Rocks of the Oceans and Continents) was born in 1999 at the Max Planck Institute in Mainz (Germany) under the leadership of A. W. Hofmann and B. Sarbas. For 25 years, GEOROC has served the geochemical community. Since 2021 the database has been curated and further developed from its new home at the University of Göttingen. Historically, geochemical data acquisition has been done by local studies and research groups. The lack of common data standards in method and acquisition reporting (metadata, vocabularies, etc.) and data formats did not allow for easy data accessibility and reuse. As the amount of published geochemical data has grown, making global compilations of well-curated geochemical data with harmonized metadata have become an urgent task. This is the core mission of GEOROC. GEOROC now has more than 685000+ records for whole rock, glass and mineral analyses. During the past four years, the GEOROC IT infrastructure was modernized as part of the WorldFAIR funded OneGeochemistry Initiative and GEOROCs interoperability with PetDB (EarthChem) reestablished. GEOROC now also offers a data repository service where authors can publish datasets with citable DOIs. However, in the era of AI chatbots and scraping algorithms, data including geochemical tables can also be scraped from the internet into uncurated piles and fed to generalized data analysis models. In this context, the greatest strength of our well-curated data products is our expert reviewed data standard conventions, vocabularies, acquisition and metadata curation. Despite our best efforts, our community has given us very clear feedback: We need to do better, specifically with respect to data and metadata quality. Therefore, we are directing a new focus on developing data quality assessment methods in our database. These utilize statistical analysis, Machine Learning methods, and AI to aid in text analysis and metadata acquisition. Additionally, we are collaborating with our sister database GeoReM (Geological Reference Materials database) on cross-correlating reference materials and metadata between the databases in a NDFI4Earth funded project. How can we do better for our community and continue to make GEOROC a database for the future of geochemical research
The impact of multiple representations on students' understanding of vector field concepts: Implementation of simulations and sketching activities into lecture-based recitations in undergraduate physics
No full textOpen-Access-Publikationsfonds 202
Rapid loss of plastid ndh genes in slipper orchids (Cypripedioideae, Orchidaceae)
No full textOpen-Access-Publikationsfonds 202
Helicity‐Dependent Enzymatic Peptide Cyclization
No full textThe secondary structure plays a crucial role in the biological activity of peptides. Various strategies have been developed to stabilize particular peptide conformations, including sequence modifications and macrocyclization approaches. Often, the interplay between conformational constraint and flexibility is central to bioactivity. Here, we investigate how peptide α-helicity influences enzymatic head-to-tail cyclization using an engineered Sortase. We show that peptides with low helicity readily undergo intramolecular cyclization, while more rigid, helical peptides exhibit complex cyclization behaviors including cyclic dimer formation. These findings reveal that increased peptide rigidity can redirect enzymatic reactions from intramolecular to intermolecular processes, and demonstrates how changes in molecular rigidity can guide chemical reactivity. These insights can advance the design of peptide-derived materials, hydrogels, and stimuli-responsive probes