Catalytic inhibition of KAT6/KAT7 enhances the efficacy and overcomes primary and acquired resistance to Menin inhibitors in MLL leukaemia.

Understanding the molecular pathogenesis of MLL fusion oncoprotein (MLL-FP) leukaemia has spawned epigenetic therapies that have improved clinical outcomes in this often-incurable disease. Using genetic and pharmacological approaches, we define the individual and combined contribution of KAT6A, KAT6B and KAT7, in MLL-FP leukaemia. Whilst inhibition of KAT6A/B is efficacious in some pre-clinical models, simultaneous targeting of KAT7, with the novel inhibitor PF-9363, increases the therapeutic efficacy.

The COSMOS Registry of CytoSorb Hemoadsorption Therapy in Critically Ill Patients: Protocol for an International, Prospective Registry.

Background: Extracorporeal blood purification with CytoSorb has been increasingly used as an adjunctive therapy in several hyperinflammatory critical care conditions, as well as to remove elevated levels of myoglobin or bilirubin in patients with rhabdomyolysis or liver failure. Despite the increasing worldwide use of hemoadsorption, data from large international multicenter studies are still lacking.

Objective: The COSMOS (CytoSorb Treatment Of Critically Ill Patients) registry is a company-sponsored registry by CytoSorbents Corporation and CytoSorbents Medical Inc.

Environmental activity-based protein profiling for function-driven enzyme discovery from natural communities.

Background: Microbial communities are important drivers of global biogeochemical cycles, xenobiotic detoxification, as well as organic matter decomposition. Their major metabolic role in ecosystem functioning is ensured by a unique set of enzymes, providing a tremendous yet mostly hidden enzymatic potential. Exploring this enzymatic repertoire is therefore not only relevant for a better understanding of how microorganisms function in their natural environment, and thus for ecological research, but further turns microbial communities, in particular from extreme habitats, into a valuable resource for the discovery of novel enzymes with potential applications in biotechnology.

Closed and open superconducting microwave waveguide networks as a model for quantum graphs.

We report on high-precision measurements that were performed with superconducting waveguide networks with the geometry of a tetrahedral and a honeycomb graph. They consist of junctions of valency three that connect straight rectangular waveguides of equal width but incommensurable lengths. The experiments were performed in the frequency range of a single transversal mode, where the associated Helmholtz equation is effectively one-dimensional and waveguide networks may serve as models of quantum graphs with the joints and waveguides corresponding to the vertices and bonds.

Benchmarking antibody clustering methods using sequence, structural, and machine learning similarity measures for antibody discovery applications.

Antibodies are proteins produced by our immune system that have been harnessed as biotherapeutics. The discovery of antibody-based therapeutics relies on analyzing large volumes of diverse sequences coming from phage display or animal immunizations. Identification of suitable therapeutic candidates is achieved by grouping the sequences by their similarity and subsequent selection of a diverse set of antibodies for further tests.