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Both the particle based Direct Simulation Monte Carlo (DSMC) method and a compressible Navier-Stokes based continuum method are used to investigate the flow inside micronozzles and to predict the performance of such devices. For the Navier-Stokes approach, both slip and no-slip boundary conditions are applied. Moreover, the two methods have been coupled to be used together in a hybrid particle-continuum approach: the continuum domain was then investigated by solving the Navier-Stokes equations with slip wall boundary condition, whereas the region of rarefied regime was studied by DSMC. The section where the domain was split was shown to have a great influence in the prediction of the nozzle performance.

Huntington’s disease (HD) is a neurodegenerative disorder caused by CAG-repeat expansions in the huntingtin (HTT) gene. The resulting mutant HTT (mHTT) protein induces toxicity and cell death via multiple mechanisms and no effective therapy is available. Here, we employ a genome-wide screening in pluripotent mouse embryonic stem cells (ESCs) to identify suppressors of mHTT toxicity. Among the identified suppressors, linked to HD-associated processes, we focus on Metal response element binding transcription factor 1 (Mtf1). Forced expression of Mtf1 counteracts cell death and oxidative stress caused by mHTT in mouse ESCs and in human neuronal precursor cells. In zebrafish, Mtf1 reduces malformations and apoptosis induced by mHTT. In R6/2 mice, Mtf1 ablates motor defects and reduces mHTT aggregates and oxidative stress. Our screening strategy enables a quick in vitro identification of promising suppressor genes and their validation in vivo, and it can be applied to other monogenic diseases.