Abstract: The present disclosure provides methods and compositions for stem cell differentiation. In some examples, the stem cell is a pluripotent stem cell (PSC). The PSC may comprise a nucleic acid comprising an open reading frame encoding one or more transcription factors, one or more transcription factors, or an activator of transcription of the open reading frame encoding one or more transcription factors.

Abstract: The present disclosure provides transcription factors and methods for stem cell differentiation into hepatocytes or hepatic cells. In some examples, a pluripotent stem cell (PSC) comprises a nucleic acid. In some examples, the nucleic acid comprises an open reading frame encoding one or more transcription factors, one or more transcription factors, or an activator of transcription of the open reading frame encoding one or more transcription factors. In some examples, the nucleic acid comprising an open reading frame encoding one or more transcription factors, the one or more transcription factors, or the activator of transcription of the open reading frame encoding one or more transcription factors induces differentiation of the PSC into a hepatocyte or a hepatic cell.

Abstract: The present disclosure provides highly multiplexed base editing methods and compositions that minimize the induction of DNA damage sensors in eukaryotic cells and maintain cell viability. The disclosed base editing methods improve the survival of eukaryotic cells after large-scale genome editing. These methods are based upon the discovery that use of a dead Cas9 base editor and optimal cell conditions during and after base editing enhances cells' tolerance to and survival following thousands of edits to the genome. Optimal cell conditions after base editing include the use of a combination of small molecule factors and/or inhibitors. These methods are facilitated by the design and use of tens to hundreds to thousands of gRNAs for guiding the base editor to the target sequences. The disclosed methods are capable of inducing between ten and 300,000 edits to the genome of a eukaryotic cell.

Abstract: A catching game is played by pendently supporting a plurality of playing cards from a device. The device is operated by one of the players to release at least one card. The released card falls under the influence of gravity and the air and falls in an unpredictable trajectory. A player must catch the card before it falls to an underlying surface.