Abstract: Methods and compositions for introducing genetic mutations into non-human animal cells are provided. These cells can be used to produce animal models of human disease. In some embodiments, the genetic mutations are flanked by DNA sequences that are “humanized” to match homologous DNA sequences. In some embodiments, the animal model is a large mammalian model for an inherited metabolic disorder. In some embodiments, the animal model is a pig model for phenylketonuria (PKU) created by introducing a missense mutation into exon 8 of the Pah gene.

Abstract: In one aspect, a computer-implemented method of performing multi-user design negotiation on a computer-aided design (CAD) software is disclosed. The method includes: receiving, from a first user, a design change to the geometric shape design, and obtaining information of the design change implementable on a CAD model of the geometric shape design through the CAD software; storing the information of the design change as a design change suggestion (DCS) object; transmitting the DCS object, together with the CAD model, to a second user; and receiving, from the second user, an instruction to the DCS object, and performing an operation corresponding to the instruction to the DCS object. In response to a what-if instruction, the operation is a what-if operation to the geometric shape design with the design change according to the DCS object. In response to an accepting or rejection instruction, the operation includes accepting or rejecting the design change.

Abstract: In one aspect, a computer-implemented method of performing multi-user design negotiation on a computer-aided design (CAD) software is disclosed. The method includes: receiving, from a first user, a design change to the geometric shape design, and obtaining information of the design change implementable on a CAD model of the geometric shape design through the CAD software; storing the information of the design change as a design change suggestion (DCS) object; transmitting the DCS object, together with the CAD model, to a second user; and receiving, from the second user, an instruction to the DCS object, and performing an operation corresponding to the instruction to the DCS object. In response to a what-if instruction, the operation is a what-if operation to the geometric shape design with the design change according to the DCS object. In response to an accepting or rejection instruction, the operation includes accepting or rejecting the design change.