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Hardcore Gamer Profiling
(2018)
Hierarchy-aware Learning of Sequential Tool Usage via Semi-automatically Constructed Taxonomies
(2020)
Highlighting Thermal Post-Treatment for Improving Long-Term Media-Tightness of Polymer-Metal Hybrids
(2021)
Integrated laser based pre‐tempering at laser welding of AISI 1045 steel by using 3D‐scanner optics
(2021)
Intelligente Lastkollektivoptimierung für Erprobungen von elektrischen und hybriden Antriebssträngen
(2019)
Learning for E-Learning
(2020)
Lower bounds on the sum of 25th-powers of univariates lead to complete derandomization of PIT
(2020)
Lösungsansätze
(2021)
The over-expression and aggregation of α-synuclein (αSyn) are linked to the onset and pathology of Parkinson's disease. Native monomeric αSyn exists in an intrinsically disordered ensemble of interconverting conformations, which has made its therapeutic targeting by small molecules highly challenging. Nonetheless, here we successfully target the monomeric structural ensemble of αSyn and thereby identify novel drug-like small molecules that impact multiple pathogenic processes. Using a surface plasmon resonance high-throughput screen, in which monomeric αSyn is incubated with microchips arrayed with tethered compounds, we identified novel αSyn interacting drug-like compounds. Because these small molecules could impact a variety of αSyn forms present in the ensemble, we tested representative hits for impact on multiple αSyn malfunctions in vitro and in cells including aggregation and perturbation of vesicular dynamics. We thereby identified a compound that inhibits αSyn misfolding and is neuroprotective, multiple compounds that restore phagocytosis impaired by αSyn overexpression, and a compound blocking cellular transmission of αSyn. Our studies demonstrate that drug-like small molecules that interact with native αSyn can impact a variety of its pathological processes. Thus, targeting the intrinsically disordered ensemble of αSyn offers a unique approach to the development of small molecule research tools and therapeutics for Parkinson's disease.
On the road again: Wie kann die Arbeitsgestaltung zur Arbeitsfreude bei mobiler Arbeit beitragen?
(2020)
One Single Click is enough – an Empirical Study on Human Threats in Family Firm Cyber Security
(2021)
Optimierung der Oberflächengüte additiv gefertigter transmittierender Optiken mittels Dip-Coating
(2018)
Organische Chemie
(2021)
Organizational Aspects of Cyber Security in Family Firms – an Empirical Study of German Companies
(2021)
Potential Benefits of Enterprise Architecture Management in the Digital Transformation Process
(2020)
Potentials of Digital Business Models – Empirical investigation of data driven impacts in industry
(2018)
Preliminary study: Polishing force measurement by viscosity - the return of ketchup polishing
(2021)