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Acute myeloid leukemia (AML) is an aggressive cancer with very poor outcomes. To identify additional drivers of leukemogenesis, we analyzed sequencing data from 1,727 unique individual patients with AML, which revealed mutations in ubiquitin ligase family genes in 11.2% of samples from adult patients with AML with mutual exclusivity. The SKP1/CUL1/F-box (SCF) E3 ubiquitin ligase complex gene, FBXO11, was the most significantly downregulated gene of the SCF complex in AML. We found that FBXO11 interacts with and catalyzes K63-linked ubiquitination of LONP1 in the cytosol, to promote LONP1 entry into mitochondria. We show that depletion of FBXO11 or LONP1 reduced mitochondrial respiration through impaired LONP1 chaperone activity to assemble electron transport chain Complex IV. Reduced mitochondrial respiration secondary to FBXO11 or LONP1 depletion imparted myeloid-biased stem cell properties in primary CD34+ hematopoietic stem and progenitor cells (HSPCs) in vitro. In a human xenograft model, depletion of FBXO11 cooperated with AML1-ETO and mutant KRASG12D to generate serially transplantable AML. Our findings suggest that reduced FBXO11 cooperates to initiate AML by priming HSPC for myeloid-biased self renewal through attenuation of LONP1-mediated regulation of mitochondrial respiration.

Energiegenossenschaften, in denen sich Burger(innen) ehrenamtlich engagieren, sind zu einem Symbol fur eine burgernahe Energiewende geworden. Neue Energiegenossenschaften werden jedoch kaum noch gegrundet, weil sie nach der Novelle des Erneuerbare-Energien-Gesetzes gegenuber grossen Anbietern benachteiligt sind. Gefragt sind nun neue Geschaftsmodelle, die helfen, dieses Modell neben Stadtwerken und privatwirtschaftlichen Versorgern auf dem Energiemarkt zu etablieren. So mussen die Genossenschaftsmitglieder etwa Know-how aufbauen, hauptamtliche Stellen schaffen und Risikokapital mobilisieren. Keywords: EEG, energy cooperatives, energy transition, founding rates, participation

Energiegenossenschaften, in denen sich Bürger(innen) ehrenamtlich engagieren, sind zu einem Symbol für eine bürgernahe Energiewende geworden.Neue Energiegenossenschaften werden jedoch kaum noch gegründet, weil sie nach der Novelle des Erneuerbare-Energien-Gesetzes gegenüber großen Anbietern benachteiligt sind. Gefragt sind nun neue Geschäftsmodelle, die helfen, dieses Modell neben Stadtwerken und privatwirtschaftlichen Versorgern auf dem Energiemarkt zu etablieren. So müssen die Genossenschaftsmitglieder etwa Know-how aufbauen, hauptamtliche Stellen schaffen und Risikokapital mobilisieren.

Energiegenossenschaften, in denen sich Bürger(innen) ehrenamtlich engagieren, sind zu einem Symbol für eine bürgernahe Energiewende geworden.Neue Energiegenossenschaften werden jedoch kaum noch gegründet, weil sie nach der Novelle des Erneuerbare-Energien-Gesetzes gegenüber großen Anbietern benachteiligt sind. Gefragt sind nun neue Geschäftsmodelle, die helfen, dieses Modell neben Stadtwerken und privatwirtschaftlichen Versorgern auf dem Energiemarkt zu etablieren. So müssen die Genossenschaftsmitglieder etwa Know-how aufbauen, hauptamtliche Stellen schaffen und Risikokapital mobilisieren.

Acute myeloid leukemia (AML) is an aggressive cancer with very poor outcomes. To identify additional drivers of leukemogenesis, we analyzed sequence data from 1,727 unique individual AML patients, which revealed mutations in ubiquitin ligase family genes in 11.2% of adult AML samples with mutual exclusivity. The Skp1/Cul1/Fbox (SCF) E3 ubiquitin ligase complex gene FBXO11 was the most significantly downregulated gene of the SCF complex in AML. FBXO11 catalyzes K63-linked ubiquitination of a novel target, LONP1, which promotes entry into mitochondria, thereby enhancing mitochondrial respiration. Reduced mitochondrial respiration secondary to FBXO11 depletion imparts myeloid-biased stem cell properties in primary CD34+ hematopoietic stem progenitor cells (HSPC). In a human xenograft model, depletion of FBXO11 cooperated with AML1-ETO and mutant KRASG12D to generate serially transplantable AML enriched for primitive cells. Our findings suggest that reduced FBXO11 primes HSPC for myeloid-biased self-renewal through attenuation of LONP1-mediated regulation of mitochondrial respiration.

Transformation of energy systems is influencing economic policy agendas all over the world, particularly so in industrialized countries. In this process, Germany has taken a pioneering role. Technical innovations, institutional frameworks, and business models established there are of interest for other countries trying to achieve broader use of renewable energies. Energy cooperatives have been an important building block of the energy transition in Germany, though their practical importance is neither quantitatively nor qualitatively reflected in the academic literature. Drawing on recently collected data, this paper presents an overview of German energy cooperatives in terms of their (1) organization, (2) membership, and (3) financing. We then review theories from economics and the social sciences that, on various levels, have been used to analyze cooperatives in other fields or other forms of community-driven organization. We discuss how these theories could be applied for a better understanding of energy cooperatives, derive a preliminary research agenda and assess the scope for interdisciplinary work among economists, sociologists, and other related disciplines.

A theoretical variation between the two distinct light–matter coupling regimes, namely weak and strong coupling, becomes uniquely feasible in open optical Fabry—Pérot microcavities with low mode volume, as discussed here. In combination with monolayers of transition-metal dichalcogenides (TMDCs) such as WS 2 , which exhibits a large exciton oscillator strength and binding energy, the room-temperature observation of hybrid bosonic quasiparticles, referred to as exciton–polaritons and characterized by a Rabi splitting, comes into reach. In this context, our simulations using the transfer-matrix method show how to tailor and alter the coupling strength actively by varying the relative field strength at the excitons’ position – exploiting a tunable cavity length, a transparent PMMA spacer layer and angle-dependencies of optical resonances. Continuously tunable coupling for future experiments is hereby proposed, capable of real-time adjustable Rabi splitting as well as switching between the two coupling regimes. Being nearly independent of the chosen material, the suggested structure could also be used in the context of light–matter-coupling experiments with quantum dots, molecules or quantum wells. While the adjustable polariton energy levels could be utilized for polariton-chemistry or optical sensing, cavities that allow working at the exceptional point promise the exploration of topological properties of that point.

A theoretical variation between the two distinct light-matter coupling regimes, namely weak and strong coupling, becomes uniquely feasible in open optical Fabry-Pérot microcavities with low mode volume, as discussed here. In combination with monolayers of transition-metal dichalcogenides (TMDCs) such as WS2, which exhibits a large exciton oscillator strength and binding energy, the room-temperature observation of hybrid bosonic quasiparticles, referred to as exciton-polaritons and characterized by a Rabi splitting, comes into reach. In this context, our simulations using the transfer-matrix method show how to tailor and alter the coupling strength actively by varying the relative field strength at the excitons' position - exploiting a tunable cavity length, a transparent PMMA spacer layer and angle-dependencies of optical resonances. Continuously tunable coupling for future experiments is hereby proposed, capable of real-time adjustable Rabi splitting as well as switching between the two coupling regimes. Being nearly independent of the chosen material, the suggested structure could also be used in the context of light-matter-coupling experiments with quantum dots, molecules or quantum wells. While the adjustable polariton energy levels could be utilized for polariton-chemistry or optical sensing, cavities that allow working at the exceptional point promise the exploration of topological properties of that point.

Light-matter interaction with two-dimensional materials gained significant attention in recent years leading to the reporting of weak and strong coupling regimes, and effective nano-laser operation with various structures. Particularly, future applications involving monolayer materials in waveguide-coupled on-chip integrated circuitry and valleytronic nanophotonics require controlling, directing and optimizing photoluminescence. In this context, photoluminescence enhancement from monolayer transition-metal dichalcogenides on patterned semiconducting substrates becomes attractive. It is demonstrated in our work using focussed-ion-beam-etched GaP and monolayer WS2 suspended on hexagonal-BN buffer sheets. We present a unique optical microcavity approach capable of both efficient in-plane and out-of-plane confinement of light, which results in a WS2 photoluminescence enhancement by a factor of 10 compared to the unstructured substrate at room temperature. The key concept is the combination of interference effects in both the horizontal direction using a bull's-eye-shaped circular Bragg grating and in vertical direction by means of a multiple reflection model with optimized etch depth of circular air-GaP structures for maximum constructive interference effects of the applied pump and expected emission light.