165 research outputs found
Raman-Spektroskopie für die Echtzeitdetektion von diatomaren Spurengasen
No full textAuthor Severin Hager-Roiser, BScAbweichender Titel laut Übersetzung der Verfasserin/des VerfassersMasterarbeit Johannes Kepler Universität Linz 2025Arbeit gesperr
Target deconvolution of the HDAC pharmacopoeia highlights MBLAC2 as a common off-target
No full textThis dataset contains the untargeted lipidomics data for the publication Lechner et al. 2022 "Target deconvolution of the HDAC pharmacopoeia highlights MBLAC2 as a common off-target". The dataset has also been submitted to MetaboLight repository with ID "MTBLS3557". Please refer to the MetaboLight repository for the most up-to-date datasets.
Publication abstract:
Histone deacetylase (HDAC) targeting drugs have entered the pharmacopoeia in the 2000s. However, some enigmatic phenotypes suggest off-target engagement. Here, we developed a quantitative chemical proteomics assay using immobilized HDAC inhibitors and mass spectrometry that we deployed to establish the target landscape of 53 drugs. The assay covers 9 of the 11 human zinc dependent HDACs, questions the reported selectivity of some widely-used molecules, notably for HDAC6, and delineates how the composition of HDAC complexes influences drug potency. Unexpectedly, metallo-beta-lactamase domain-containing protein 2 (MBLAC2) featured as a frequent off-target of hydroxamate drugs. This poorly characterized palmitoyl-CoA hydrolase is inhibited by 24 HDAC inhibitors at low nM potency. MBLAC2 enzymatic inhibition and knock down led to the accumulation of extracellular vesicles. Given the importance of extracellular vesicle biology in neurological diseases and cancer, this HDAC-independent drug effect may qualify MBLAC2 as a target for drug discovery
Study of the degradation process of polyimide induced by high energetic ion irradiation
No full textOnTEAM metadata: GDSID: DOC-2008-Dec-144; Attribute ID: LIBRARY-thesis_diss-2008-020; Title: [GSI Diss 2008-19] Study of the degradation process of polyimide induced by high energetic ion irradiation [19.09.2008]; Author(s): Severin, Daniel; Corporate author(s): ; Publication date: 20081215; Creator: manton; Creation date: 15.12.2008 15:08:01; Change date: 30.09.2010 15:02:28; Access: Welt; Attribute type: Text.Thesis.Diss; Directory path: ['GSI Publications', 'GSI as Publisher']; Attribute path: ['Infrastructure', 'Library and Documentation', 'thesis_diss', 'Added in 2008']; File name(s): ['DOC-2008-Dec-144-1.pdf']; File title(s): ['']; File access: ['GSI-intern'
Les deux « grammaires générales » de Johann Severin Vater sont-elles « générales »
No full textABSTRACT: In 1801, Johann Severin Vater published «Versuch einer allgemeinen Sprachlehre» («An Essay of a General Grammar») and in 1805,
Lehrbuch der allgemeinen Grammatik
(«A Manual of General Grammar»). Both titles include the qualitative adjective «general» by which Vater explicitly refers to the tradition of general grammars, initiated by Port-Royal. Moreover, Vater underlines several times in both texts the «general» nature of his analysis. Today however, both grammars are often described as entirely or at least partially historical and comparative works. This article deals with the principles of Vater’s analysis, his conception of general grammar and its application to linguistic facts. It seems possible to show, in accordance with the conviction of their author, that the two grammars actually fit in the tradition of general grammars and that «An Essay of a General Grammar» in particular represents a remarkable example of it.</jats:p
Les deux « grammaires générales » de Johann Severin Vater sont-elles « générales »
No full textABSTRACT: In 1801, Johann Severin Vater published «Versuch einer allgemeinen Sprachlehre» («An Essay of a General Grammar») and in 1805,
Lehrbuch der allgemeinen Grammatik
(«A Manual of General Grammar»). Both titles include the qualitative adjective «general» by which Vater explicitly refers to the tradition of general grammars, initiated by Port-Royal. Moreover, Vater underlines several times in both texts the «general» nature of his analysis. Today however, both grammars are often described as entirely or at least partially historical and comparative works. This article deals with the principles of Vater’s analysis, his conception of general grammar and its application to linguistic facts. It seems possible to show, in accordance with the conviction of their author, that the two grammars actually fit in the tradition of general grammars and that «An Essay of a General Grammar» in particular represents a remarkable example of it.RÉSUMÉ: En 1801 Johann Severin Vater publie Versuch einer allgemeinen Sprachlehre («Essai d’une grammaire générale») et en 1805, Lehrbuch der allgemeinen Grammatik («Manuel de la grammaire générale»). Dans les deux titres Vater qualifie donc son étude de «générale», qualification que, de plus, il revendique plusieurs fois dans les deux textes et par laquelle il renvoie à la tradition des grammaires générales ou rationnelles qui fut inaugurée par les Messieurs de Port-Royal. Néanmoins, plusieurs commentateurs modernes ont considéré que ces deux ouvrages relèvent seulement en partie ou même ne relèvent pas du tout de cette tradition mais s’inscrivent — au moins partiellement — dans le courant des grammaires historiques et comparées qui prend son essor à cette époque. L’étude cherche alors à élucider les principes d’analyse de Vater dans ces deux ouvrages, la conception de la grammaire générale de l’auteur et sa mise en application. Il nous semble possible de démontrer que, conformément à la conviction de l’auteur, aussi bien l’Essai que le Manuel relèvent bel et bien de la tradition des grammaires générales et que notamment l’Essai en constitue une illustration remarquable.Spitzl-Dupic Friederike. Les deux « grammaires générales » de Johann Severin Vater sont-elles « générales ». In: Histoire Épistémologie Langage, tome 25, fascicule 1, 2003. Politiques linguistiques (2/2) pp. 129-150
Study on Water Source Protection - Case Study of Lake Buhui – Anina City, Caras – Severin County, Romania
No full textAbstractPlanning the protection of water sources is a necessity for complying with national legislation in the area of drinking water, namely the Water Law and European legislation - the Water Framework Directive. Adopting a coordinated approach to the protection and sustainable use of water resources, with the cooperation of all stakeholders, it ensures the sustainable use of water resources in long term for people, economy and environment. Buhui Lake is the first artificial lake in Romania, with an area of about 11 hectares, built at an altitude of 640 m for water supplying the Anina city. In the Master Plan Water-Wastewater for Caras-Severin, Buhui Lake will provide the only source of potable water for Anina - Steierdorf agglomerations. It was analyzed the evolution of the indicators for the lake raw water quality depending on the atmospheric regime and the results showed that turbidity and CBO5 are influenced by anthropogenic activity, due to controlled and uncontrolled forestry activities in the area. In these circumstances, the elaboration of the water source protection plan of the Lake Buhui is a necessity, because the activities carried out in the sanitary protection zone of water catchment area may have negative impact on the population. The integrated approach for sustainable management of water resources in the catchment area is a good practice of the European Union to be taken in case of water sources in the country. The plans undertaken to protect water sources we can identify shortcomings and problems and we can set the policy actions to address them
Editorial: Compartmental models for social interactions
No full text[No Abstract Available]National Recovery and Resilience Plan (NRRP); Mission 4 Component 2 Investment [3277]; European Union [ECS00000033, 1052]The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. This research is partially funded under the National Recovery and Resilience Plan (NRRP), and Mission 4 Component 2 Investment 1.5-Call for tender No. 3277 of 30/12/2021 of Italian Ministry of University and Research funded by the European Union-NextGenerationEU Award Number: Project code ECS00000033, Concession Decree No. 1052 of 23/06/2022 adopted by the Italian Ministry.Science Citation Index Expande
CRISPR-Cas12a has widespread off-target and dsDNA-nicking effects
No full textCas12a (Cpf1) is an RNA-guided endonuclease in the bacterial type V-A CRISPR-Cas anti-phage immune system that can be repurposed for genome editing. Cas12a can bind and cut dsDNA targets with high specificity in vivo, making it an ideal candidate for expanding the arsenal of enzymes used in precise genome editing. However, this reported high specificity contradicts Cas12a’s natural role as an immune effector against rapidly evolving phages. Here, we employed high-throughput in vitro cleavage assays to determine and compare the native cleavage specificities and activities of three different natural Cas12a orthologs (FnCas12a, LbCas12a, and AsCas12a). Surprisingly, we observed pervasive sequence-specific nicking of randomized target libraries, with strong nicking of DNA sequences containing up to four mismatches in the Cas12a-targeted DNA–RNA hybrid sequences. We also found that these nicking and cleavage activities depend on mismatch type and position and vary with Cas12a ortholog and CRISPR RNA (crRNA) sequence. Our analysis further revealed robust non-specific nicking of dsDNA when Cas12a is activated by binding to a target DNA. Together, our findings reveal that Cas12a has multiple nicking activities against dsDNA substrates and that these activities vary among different Cas12a orthologs.This research was originally published in the Journal of Biological Chemistry. Murugan, Karthik, Arun S. Seetharam, Andrew J. Severin, and Dipali G. Sashital. "CRISPR-Cas12a has widespread off-target and dsDNA-nicking effects." Journal of Biological Chemistry (2020): jbc-RA120. © the Author(s). doi: 10.1074/jbc.RA120.012933.</p
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